aromaticity

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CONTENTS 

UNIT-I 

LESSON: 1 – AROMATICITY 

1.0. AIMS AND OBJECTIVES 

1.1. INTRODUCTION 

1.2. CONDITIONS FOR AROMATICITY 

1.3. HUCKEL (4n+2) RULE FOR AROMATICITY 

1.4. AROMATICITY OF BENZENOID AND HETEROCYCLIC COMPOUNDS 

1.4.1. BENZENOID COMPOUNDS 

1.4.1.1. Six-membered rings 

1.4.1.2. Phenanthrene and anthracene 

1.4.1.3. Heterocyclic compounds 

1.4.2. NON-BENZENOID AROMATIC COMPOUNDS 

1.4.2.1. Annulenes 

1.4.2.2. Azulenes 

1.4.2.3. Ferrocene 

1.5. AROMATIC, ANTIAROMATIC AND NON-AROMATIC COMPOUNDS 

1.5.1. Cyclopentadiene 

1.5.2. Furan 

1.5.3. Cyclooctatetraene 

1.5.4. Cyclopropenium salts 

1.5.4.1. Cyclopropene 

1.5.4.2. Cyclopropenyl Cation 

1.5.4.3. Cyclopropenyl anion 

1.5.5. Cyclobutenium salts 

1.5.6. Tropylium salts 

1.5.7. Aromatic or Non aromatic 

1.6. LET US SUM UP 

1.7. CHECK YOUR PROGRESS 

1.8. POINT FOR DISCUSSION 

1.9. REFERENCES 


The aim is to motivate and enable a comprehensive knowledge on configurational and 

conformational analysis to the students. 

On successful completion of this lesson the student should have: 

* Understand the aromaticity, anti-aromaticity and non-aromaticity in organic compounds. 


Aromaticity can now be defined as the ability to sustain an induced ring current. A 

compound with this ability is called diatropic.There are several methods of determining whether 

a compound can sustain a ring current, but the most important one is based on NMR chemical 

1


shifts. In order to understand this, it is necessary to remember that, as a general rule, the value of 

the chemical shift of a proton in NMR spectrum depends on the electron density of its bond, the 

greater the density of the electron cloud surrounding or partially surrounding a proton, the more 

up field is its chemical shift. 

This rule has several exceptions; one is for proton in the vicinity of an aromatic ring. 

When an external magnetic field is impulsed upon an aromatic ring the closed loop of aromatic 

electrons circulates in a diamagnetic ring current, which sends out a field of its own. 

As can be seen in the diagram, this induced field curves around and in the area of the 

proton is parallel to the external field, so that the field felt by the aromatic proton is greater than 

it would have been in the absence of the diamagnetic ring current. The protons are moved 

downfield compared to where they would be if electron density were the only factor. The 

ordinary olefinic hydrogens are found at 5 to 6d, while the hydrogens of benzene rings are 

located at about 7 to 8d. 

induced field 

outside field 

If the proton attached to the ring are shifted downfield from the normal olefinic region, 

we can conclude that the molecule is diatropic and hence aromatic. In addition, if the compound 

is diatropic, these will be shifted up field. This method cannot be applied to compounds that have 

no protons in either category e.g. the dianion of squaric acid. 

1.2. CONDITIONS FOR AROMATICITY 

For a compound to be aromatic one looks for diamagnetic ring current, equal or 

approximately equal bond distances, planarity, chemical stability and the ability to undergo 

aromatic substitution. 

1. The structure must be cyclic. 

2. The ring must be planar. 

2 

3. Each of the rings must be SP hybridized (or occasionally SP hybridized) and have an 

unhybridized p-orbital. 

4. The total number of p electrons in the molecule or ion should be ( 4n 

+ 2) 

where 

n = 0, 

1, 

2, 

3,...... 

5. The unhybridized p-orbital must overlap to give a continuous ring of parallel orbital (the 

condition of planarity is for effective overlap). 

6. This delocalization of p electrons over the ring result in the lowering of the electronic energy 

2


1.3. HUCKEL (4n+2) RULE FOR AROMATICITY 

Huckel carried out molecular orbital calculation on monocyclic systems CnH n containing 

n p electrons and each carbon atom providing one p electrons and as a result connected aromatic 

stability (high delocalization energy or high resonance energy) with the presence of ( 4n 

+ 2) 

p electrons in a closed shell. 

To be aromatic, a molecule must have 2(n=0), 6(n=1), 10(n=2)…….. p electrons. In this 

description of aromaticity, no mention is made of the number of carbon atom in the ring; the 

essential requirement is the presence of ( 4n 

+ 2) 

p electrons. Another requirement, for 

Aromaticity is planarity of the ring. If the ring is not planar, overlap of the p-orbital is diminished 

or absent. Thus if a molecule is a monocyclic planar system and contains (4n+2) p electrons 

that molecule will exhibit aromatic character (i.e.) will have unusual stability. For benzene ring 

or shell of six p electrons (i.e.) bonding molecular orbital are doubly filled. 

4n + 2 

E 

No. of p electrons 

Non-bonding 

1.4. AROMATICITY OF BENZENOID AND HETEROCYCLIC COMPOUNDS 

1.4.1. BENZENOID COMPOUNDS 

1.4.1.1. Six-membered rings 

Not only is the benzene ring aromatic but so many heterocyclic analogs in which one or 

more hetero atoms replace carbon in the ring. When nitrogen is the hetero atom, little difference 

is made in the sextet and unshared pair of the nitrogen does not participate in the Aromaticity or 

pyridinium ions are still aromatic. 

However for nitrogen heterocycles there are more significant canonical forms than for 

benzene. (Eg: 1) 

_ + 

N_ 

_ 

_ 

O_ 

O_ 

+ 

(1) (2) (3) 

3


Where oxygen or sulphur is the hetero atom, it must be present in its ionic form (2) in 

order to possess the valence of (3) that participation in such a system demands. Thus, pyran (3) is 

not aromatic but the pyridinium ion is. (2)In systems of fused six-membered aromatic rings, the 

principal canonical forms are usually not all equivalent. (4) has a central double bond and thus 

different from the other two canonical forms of naphthalene, which are equivalent to each other. 

7 

6 

8 

5 

(4) 

1 

4 

2 

3 

Naphthalene 

If we assume that three forms contribute equally, the 1, 2 bonds have more double bond 

character than 2, 3 bonds. Molecular orbital calculations shows bond order of 1.724 and 1.603 

respectively (compare benzene 1.667). in agreement with these predictions the 1,2 and 2,3 bond 

distances are 1.36 and 1.415Å respectively and ozone preferentially attacks the 1,2 bond. This 

non equivalency of bonds, called partial bond fixation is found in nearly all fused aromatic 

systems. 

1.4.1.2. Phenanthrene and anthracene 

In phenanthrene, where the 9,10 bond is a single bond in only one of five forms, bond 

fixation becomes extreme and this bond is readily attacked by many reagents. 

3 

2 

4 

1 

5 

6 

9 

7 

8 

10 

A B C 

D E 

The resonance energies of fused systems increase as the number of principal canonical 

forms increases, thus for benzene, naphthalene, anthracene and phenanthracene, for which we 

can draw, respectively. Two, three, four and five principal canonical forms, the resonance 

energies are respectively 36, 61, 84 and 92 KCal / Mol ,calculated from heat of combustion data. 

4


1.4.1.3. Heterocyclic compounds 

7 

6 

8 9 

5 

10 

Anthracene 

Heterocyclic compounds can also be aromatic since for the application of Huckel’s rule 

what one needs is a ring of atoms, all with unhybridized ‘p’ orbital in a planar arrangement in 

order that the ‘p’ orbital overlaps in a continuous ring. Thus the heterocyclic compounds are all 

aromatic. 

(1) Pyrrole, furan and thiophene in fact represent 1-hetero 2, 4-cyclopentadiene and a 

butadiene unit bridged by a hetero atom bearing lone pairs. In electronic structure these three 

compounds are similar to cyclopentadienyl anion. 

Pyridine 

.. .. 

.. 

N S.. O.. 

.. 

_ 

H 

_ 

Pyrrole Thiophene Furan 

1 

4 

2 

3 

cyclopentadienyl 

anion(6pelectrons) 

Both benzene and pyridine have a similar Kekule structure. Pyridine with resonance 

energy of 27KCal( 113KJ 

) per mole shows typical characters of aromatic compound. The 

nitrogen atom in pyridine is 

this along with one each from the five carbon atoms give pyridine a sextet of p electrons similar 

2 

SP hybridized nitrogen donates one electron to the p system and 

N .. 

Pyridine 

Pyridine 

to that in benzene. The non-bonding electrons of nitrogen are in an 

plane of the ring and these electrons do not interact with the p system of the ring. 

H 

H 

H 

SP 2 

H 

N 

.. 

H 

5 

2 

SP orbital which lies in the


The unshared pair of non-bonding electrons confers on pyridine the properties of a weak 

base. Thus pyridine protonates to yield the pyridinium ion which retains its aromatic character 

since the process does not disturb the electrons of the aromatic sextet. 

Pyrrole 

In pyrrole only four p electrons are contributed by the carbon atoms of the ring. To make 

2 

an aromatic sextet the SP hybridized nitrogen then contributes two electrons. Pyrrole is far less 

basic than pyridine because these apparently unshared electrons are in the aromatic p cloud. 

These are not readily available for bonding with proton (protonation). 

Furan and thiophene 

Both furan and thiophene have two pairs of electrons on the hetero atoms and therefore, 

combine the structural features of pyrrole and pyridine. One pair of electrons is in the sixelectron 

p system and other lies in the plane of the ring. 

Furan 

O S 

1.4.2. NON-BENZENOID AROMATIC COMPOUNDS 

1.4.2.1. Annulenes 

Thiophene 

Conjugated monocyclic polyenes, CnHn in which n ³ 10 are usually called annulenes, and 

were prepared by sondheimer et al (1962) to test the Huckel’s rule. The annulenes prepared have 

n= 12, 14, 16, 18, 20, 24, 30. Out of these only [14], [18], [30] annulenes are ( 4n 

+ 2) 

p electrons 

molecules, whereas the rest are 4n molecules, some examples are 

6


H 

H 

H H 

[14] annulene 

1.4.2.2. Azulenes 

H 

H 

H 

H 

H 

H 

[18] annulene 

H H 

dehydro [14] annulene 

Azulene is one of the few completely conjugated non-benzenoid hydrocarbons that 

appear to have appreciable aromatic stabilization. The parent hydrocarbon and many of its 

derivatives have been well characterized and are stable compounds. The structure of azulene 

itself has been determined by both X-ray and electron-diffraction measurements. The peripheral 

bond lengths are in the aromatic range and show no regular alteration. The bond shared by the 

two rings is significantly longer, indicating dominant single-bond character. 

Azulene has resonance energy of 49 kcal/mol. It has a substantial dipole moment (1.0 D) 

while the dipole moment of the isomeric compound naphthalene is 0. That presence of dipole 

moment in azulene suggests that charge separation exists in the molecule and that each ring 

approximates to six p-electron system. Azulene may be regarded as a combination of aromatic 

cyclopentadienyl anion and aromatic cycloheptatrienyl cation. Thus in valence bond terms, the 

ionic structure of azulene (a non-benzenoid aromatic compound) is an important contributor to 

the resonance bond. 

Azulene 

1.4.2.3. Ferrocene 

Ring resembles the 

cyclheptatrienyl cation 

Very much like 

the aromatic 

cyclopentadieny anion 

Charge-separated resonance structure 

Ferrocene is an aromatic compound (non-benzenoid) which is highly stable and 

undergoes a number of electrophilic aromatic substitutions. The carbon-carbon bond distances 

7


are also 1.40 Å and carbon-iron bond distances are all 2.04 Å. Due to these structural features the 

compounds like Ferrocene they are called “Sandwich” compounds. The carbon iron bonding in 

Ferrocene may be looked upon as a result from overlap between the inner lobes of the ‘p’ orbital 

of the cyclopentadienyl anions and 3d orbital of the iron atoms. A noteworthy feature of many 

organic derivatives of transition metals is that the organic group is bonded to the metal through 

the p system rather than by a ‘s’bond as in (benzene/tricarbonyl chromium). 

_ Fe +2 + 

Cyclopentadienyl 

anion(6pelectrons) 

aromatic 

Fe 

Dicyclopentadienyl iron 

(ferrocene) 

[(C 5H 5) - ] 2Fe +2 

OC 

+ 

Cr 

CO 

CO 

(Benzene) 

tricarbonyl 

chromium 

1.5. AROMATIC, ANTIAROMATIC AND NON-AROMATIC COMPOUNDS 

Cyclic conjugated polyenes can be aromatic (Eg: benzene) provided they contain ( 4n 

+ 2) 

electrons (n=0, 1, 3…). Aromatic structures are more stable when compared with their open 

chain counter parts. In contrast, a conjugated cyclic system with 4n p electrons is called anti 

aromatic since in it p electron delocalization results in increase in energy (destabilization). 

Cyclobutadiene is thus an antiaromatic compound. Since the delocalization of the p electrons 

results in an increase in the electronic energy. Cyclobutadiene is less stable than its open chain 

counterpart (1, 3, butadiene). 

Aromatic Anti Aromatic 

A cyclic compound in which continuous overlapping ring of p- orbital is disrupted 

sufficiently cannot be aromatic or anti aromatic (both require overlap of parallel p-orbital. It is 

termed non-aromatic or aliphatic. 

Non Aromatic 

(1,3-cyclohexadiene) 

Similar 

Stabilities 

CH 3 

CH 3 

(cis-C-2,4-hexadiene) 

8


1.5.1. Cyclopentadiene 

H 

H 

Me 3CO 

H 

Aromatic anion 

Cyclopentadiene is not aromatic, 5p electrons (n=1) (4n+1) molecules do not obey 

Huckel’s rule. Number of p electrons 4 (n=1). 4n molecule does not satisfy Huckel’s rule. 

1.5.2. Furan 

Cyclopentadienyl cation 

Cyclopentadienyl anion 

Number of p electrons 6 (n=1). (4n+2) molecule. Satisfy Huckel’s rule. It is aromatic. 

_ 

.. 

.. .. 

O N 

.. 

H 

N 

.. 

S.. 

Furan 

Pyrrole Pyridine 

Thiophene 

In this heterocyclic compound can also be aromatic. It obeys Huckel’s rule.Unhybridized 

p-orbital overlap in a continuous ring. Furan-6 electrons, n = 2, (4n+2) molecule; Pyrrole-6 

electrons, n = 2, (4n+2) molecule and Pyridine and thiophene-6 electrons, n =2, (4n+2) molecule. 

1.5.3. Cyclooctatetraene 

8 electrons (n = 2) (4n) molecules. It is a non-aromatic. Do not obey the Huckel’s rule. 

Molecules do not possess a closed shell planar configuration in the ground state. This is the 

reason for the instability or reactivity of these compounds. Monocyclic (4n) p electrons 

molecules are less stable than acyclic. This decreased stability of 4n molecules has been 

attributed to anti-aromaticity. 

9


The metal acts as an electronic source, supplying two electrons to the cyclooctatetraene. 

The resulting dianion has ten electrons (a Huckel’s number) and by planar configuration becomes 

aromatic and therefore, more stable. 

2K + 2K + 

H 

1.5.4. Cyclopropenium salts 

1.5.4.1. Cyclopropene 

H 

Cyclopropene 

Non-bonding 

3 electrons, n = 0; (4n + 3) molecule. Do not obey the Huckel’s rule. 

or 2K + 

1.5.4.2. Cyclopropenyl Cation It becomes a closed-shell (4n+2) p electron 

molecule (n = 0). It represented as a resonance hybrid. 

1.5.4.3. Cyclopropenyl anion (4n) molecule (n = 1). 

1.5.5. Cyclobutenium salts 

(4n) p electron molecule, and is in the triplet state. This is the ground state of 

Cyclobutadiene and accounts for its high instability. Other hand, loss of 2 p electrons in the 

separate non-bonding molecular orbitals produces the closed shell (4n+2) p electron molecule 

(n=0) (i.e.) cyclobutenyl di-cation. 

1.5.6. Tropylium salts 

By loss of the single p electron in the anti bonding molecular orbital gives the Tropylium 

Cation. 

2 - 

10


Tropylium anion 

1.5.7. Aromatic or Non aromatic 

6 p electrons (4n+2) (n=1) obeys the Huckel’s rule. 

8 p electrons (4n) n = 2. It does not obey the Huckel’s rule. 

H 

H 

Cycloheptatriene 

Non aromatic, 6 p electrons (4n) – n = 2. It does not obey the Huckel’s rule. Here one of 

the C is SP 3 hybridized there by preventing a completed cyclic overlapping p system. 

CH 2 

3-Methylene-1,4 Cyclohexadiene 

Non aromatic 6 electrons 

Here the methylene C is not part of the ring which has one 


3 

SP hybridized C. 

In this lesson, we: 

* Explained the conditions for aromaticity 

* Pointed out the Huckel (4n+2) rule for aromaticity 

* Explained the aromaticity of benzenoid and heterocyclic compounds 

* Discussed the non-benzenoid aromatic compounds 

* Explained the aromatic, antiaromatic and non-aromatic compounds 

11



1. Comment on the aromaticity of the compound (1) and (2). 

H H 

(1) (2) 

2. On hydrogenation anthracene liberates 116.2Kcal/mol. What is the resonance energy of 

anthracene? 


1. Why compared to [14] annulenes, [18] annulenes is more stable? 

2. Why cyclopropenone is a stable compound while Cyclopentadiene has not been 

prepared 


O 

O 

Cyclopropenone Cyclopentadienone 

1. Jerry march, Advanced Organic Chemistry, Fourth edition, Wiley India edition. 

2. P.S. Kalsi, Organic reactions and their mechanisms, Second edition, New age 

international publishers. 

12


B and C are two isomeric products. 

A B + C 

The one which has high activation energy is more stable product and this product is 

thermodynamically controlled product. The one has low activation energy is less stable product 

this product is kinetically controlled products. 

(i). Both the steps are irreversible then the product will contain more C. 

(ii). If both the steps are reversible and if the reaction is stopped before the equilibrium attain 

then also we get more kinetic controlled product C. 

(iii). If both the steps are reversible and the equilibrium is reached, then we get the B which is 

thermodynamic controlled product is formed. 

Example: 

con. H 2SO 4 

40 C 

° 

con. H 2SO 4 

160 C 

° 

SO 3H 

Naphthalene-1-sulphonicacid 

Kinetically controlled product 

SO 3H 

Naphthalene-2-sulphonicacid 

Thermodynamically controlled product 

14


2.3. MICROSCOPIC REVERSIBILITY 

In a reversible reaction the forward and reverse reactions must follow the same 

mechanism. This phenomenon is called the principle of microscopic reversibility. 

Example: 

In the dehydration of an alcohol, an olefin is format via. a carbonium ion intermediate, as 

a consequence of the principle of the microscopic reversibility, the reverse reaction i.e., the acid 

catalyzed hydration of olefin to alcohol, must involve the same carbonium ion. 

H 

C C 

OH 

H + 

- H + 

2.4. HAMMOND’S POSTULATE 

H 

C C 

OH 2 

H 2O 

- H 2O 

H 

C C 

- H + 

H + 

C C 

For any single reaction step, the geometry of the transition state resembles to the side to 

which it is closer in energy. 

Example (i): 

In the exothermic reaction the energy of transition state is closer to reactant. So the 

geometry of transition state resembles as reactant. 

Example (ii): 

In SN 1 reaction, there will be two transition state, energy of these transition state are closer 

to intermediate so the geometry of transition state resembles as intermediate. 

15


Methods that are used to determine to Reaction Mechanism: 

(i) Kinetic Methods 

(ii) Non-Kinetic Methods 

2.5. KINETIC AND NON-KINETIC METHODS OF STUDY OF REACTION 

MECHANISMS 

2.5.1. KINETIC METHODS 

2.5.1.1. PRIMARY AND SECONDARY KINETIC ISOTOPIC EFFECT 

This will observed if the C-H bond cleavage takes place in a slow step mechanism. 

Isotopic substitution will give acceptable charges, i.e., the rate of the reaction. 

O 

= 

CH 3 - C - CH 3 + Br 2 

H + or OH - 

This reaction can be catalyzed by both an acid and a base. 

The rate of the reaction depend on, 

(i) Catalyst (ii) Reactant (iii) Independent of Br2 

O 

= 

CH 3 - C - CH 3 + Br 2 

H + or OH - 

O 

= 

CH 3 - C - CH 2Br + HBr 

O 

= 

CH 3 - C - CH 2Br 

The acid or base reacts with the ketone means, the a-hydrogen is reacted and forms the enol. 

O OH 

= 

CH 3 - C - CH 3 

H + 

Enolisation involves the C-H bond cleavage. 

OH - 

slow 

- 

CH 3 - C = CH 2Br 

16


O 

= 

CH 3 - C - CH 3 

The C-H bond cleavage taking place in the reaction mechanism: 

Br2 

fast 

OH 

- 

CH 3 - C - CH 2Br 

- H + 

O 

= 

CH 3 - C - CH 2Br 

In the case of CH3-CO-CH3, the energy for C-O bond cleavage is high i.e., energy 

increases means rate decreases. 

CH3-CO-CH3 - Rate of the reaction for normal ketone is KH. 

CH3-CO-CH3 - Rate of the reaction for isotopic hydrogen presence in the ketone is KD. 

In the case of heavier isotope has lower zero point vibrational energy by giving kinetic 

energy by means of thermal energy, the energy is increased of one stage, bond is cleaved so the 

energy is increased and the rate is decreased. 

K 

K 

H 

D 

= 7 . If 

Example: 

K H is 7 or around 7 means the mechanism is correct. 

K 

D 

Consider the nitration of benzene, the mechanism of nitration of benzene was established 

by kinetic isotopic effect. 

+ 

NO 2 

step (i) 

H 

NO 2 

- H + 

step (ii) 

The above nitration involves two different steps and any one of the two steps may be rate 

determining there are two possibilities. 

(i) Step (i) slow and step (ii) fast. 

(ii) Step (i) fast and step (ii) slow. 

First let us assume step (i) is slow and step (ii) is fast. The rate constant for the nitration 

of benzene is KH. The rate constant for the nitration of benzene is KH. The rate constant for the 

nitration of deuterated benzene is KD. The step (ii) alone involves the C-H bond breaking. Here 

in this case KH=KD there is kinetic isotopic effect. 

If we consider the (ii), i.e., step (ii) as fast and (ii) as rate determining then KH is not equal 

to KD. But the experimental result shows that KH/KD = 1. There is no isotopic effect. 

The kinetic isotopic effect shows that the first step is the rate determining step and it does 

not involve the C-H bond breaking. In some of the reaction the C-H bond breaking is not the rate 

NO 2 

17


determining step. But there will be isotopic effect, even though the C-H bond breaking is not 

involved in the determining step. This effect is called the secondary kinetic isotopic effect. 

2.5.2. NON-KINETIC METHODS OF STUDY OF REACTIONMECHANISM 

Non-Kinetic method involves the following steps. 

a) Identification of product 

b) Identification of intermediate 

c) Isotopic labeling 

d) Stereo chemical evidences: 

2.5.2.1. Identification of products 

The most fundamental basis for mechanistic speculation i.e., the identification of the 

products, without such intermediate we can’t be sure which reaction actually occurs under the 

given conditions. 

This should account for all the products, relative proportion of the product and also the 

product formed by the side reaction. 

Example (i): 

CH 4 + Cl 2 

Example (ii): 

CH 3Cl + CH 2Cl 2 + CHCl 3 + CCl 4 

There will be small amount of CH3-CH3 (ethane) i.e., the • CH3 is formed. 

Chlorination of toluene yields benzyl chloride in vapor phase but if the chlorination is 

carried out in the liquid phase in the presence of AlCl3 o-chlorotoluene and p-chlorotoluene 

result. 

CH 3 

Cl 2 

hg 

CH 2Cl 

18


CH 3 

Cl 2 

Al 2O 3 

Therefore the identification of products suggests that two different chlorination 

mechanisms operate depending upon the conditions. 

2.5.2.2. Identification of the intermediate 

Among the most concrete evidence obtained about the mechanism of the reaction is that 

provided by the actual isolation and identification of one or more intermediates from the 

reactions mixtures. 

(i) Isolation of an intermediate 

It is sometimes possible to isolate an intermediate from a reaction mixture by stopping the 

reaction after a short time or by use of very mild conditions. 

Eg: Hofmann rearrangement reaction. 

CH 3 

Cl 

RCONH2 NaOBr 

RNH 2 

Amide Amine 

In these reaction three intermediates namely N-bromamide, its anion and an isocyanate 

have been isolated. 

RCONH 2 

H 2O 

OH 

RCONHBr 

- 

OBr 

RCNBr 

- OBr- RNH 2 + CO 

(ii) Trapping of intermediate 

= O 

+ 

CH 3 

Cl 

R - N = C = O 

Some times an intermediate may be detected but cannot be isolated in such cases the 

trapping reagent is added to react with the intermediate from the nature of the product the 

intermediate could be identified. 

Eg: Bromination of olefins: 

C C + Br 2 

CH 3COOH 

slow 

C C 

Br 

C C 

Br 

19


Br - 

fast 

C C 

Br Br 

If we add the external nucleophile along with the bromonium ion the external nucleophile is also 

attached CH3OH is the trapping agent. 

C C 

Br 

CH 3OH 

dibromo compound + bromoester à No reaction. 

CH 3OH + C C 

CH 3OH + C C 

Br 

(iii) Detection of an intermediate 

No reaction 

Reaction 

C C 

Br OMe 

In many cases an intermediate can’t be isolated but can be detected. 

con. HNO 3 

con. H 2SO 4 

NO 2 

Nitrobenzene 

The NO2 + , the electrophile is detected by Raman spectroscopy. In the free radical the 

unpaired electron is observed by ESR or EPR. So the formation of the radical intermediate is 

detected. 

2.5.2.3. Isotopic labeling 

This is an effective method of determining specific information about the bonds that are 

involved in a reaction. 

14 

RCOO 

+ 

BrCN 

14 

RCN + CO2 + Br 

20


Carbon has two isotopes C 14 is the radio active so we label the C in RCOO - is RC 14 OO but in the 

product C 14 is present in alkylcyanide. 

Eg: 

Ester hydrolysis whether it is acid catalysis and basic catalysis in involves two types 

cleavage. 

O 18 

H2O R - C - OR' 

= 

Mostly acyloxygen cleavage takes place. 

O 

= 

R - C - OR' 

18 

H2O 18 

RCOOH + R'OH 

18 

RCOOH + R'OH 

O 18 in the products is found out by the help of mass spectrum i.e., the acid and the alcohol 

are analysed and the heavy isotope O 18 is present in the acid i.e., confirms the acyloxygen 

cleavage present. 

2.5.2.4. Stereo Chemical evidences 

Olefins undergo addition because the double bond is rich in electron. It is a univalence 

atom so we add 2 atoms. 

(i) Two atoms are added simultaneously this is called constructed mechanism. 

C C 

Br 

If the two new bonds can add from the same side then the mechanism is called cis or syn 

addition. 

C C 

Br Br 

First the bromonium ion forms a cyclic intermediate, the second Br - goes to the other 

side i.e, the two Bromine atoms add from the opposite side then the mechanism is called trans 

addition. 

Br + 

21


(i). Addition of Bromine in olefins 

HOOC 

H 

HOOC 

C 

C 

Br 

C 

COOH 

H 

HOOC 

+ 

+ 

Br Br 

C 

COOH 

H 

HOOC 

H 

C 

C 

Br 

C 

C 

H 

COOH 

H 

COOH 

Whether cis or trans isomer, carbonium ion intermediate is formed means because of 

single bond is capable of free rotation and the two acids i.e., maleic and fumaric acid leads to the 

same product because the bulky –COOH groups in the maleic acid intermediate and hindrance 

and it forms the intermediate of trans isomer. 

If it is bromium ion intermediate means the rotation is not possible. 

If it is cyclic bromonium ion intermediate means the intermediate obtained by cis and 

trans isomers are not identical. So the products are different i.e., it retained the stereo chemistry 

of the reactant. 

HOOC 

2.5.2.5. Stereo Chemical Method 

H 

C 

COOH HOOC 

C 

C C 

Br 

H 

H 

Br 

H 

COOH 

Organic substance exhibits in stereo isomerism i.e., geometrical isomerism and optical 

isomerism in the case of optical isomerism the starting material is in meso active or racemic 

form, after the reaction is completed then also we have to see the nature or seterochemistry of the 

product. 

R S 

S 

R 

S 

R 

S 

R 

R + S 

R + S 

R 

S 

Inversion of configuration 

Racemisation 

Retention of configuration 

22


Eg: SN 1 reaction. 

Kinetics of this mechanism shows that it is first order mechanism and the nucleophile is 

not involved the rate determining step. 

I step: Formation of the carbocation 

H 

C 

CH 3 

The carbocation SN 1 reaction is a symmetry reaction. 

II step: Attacks of nucleophile: 

CH 

CH 3 

Br CH 

CH 3 

fast 

+ OH 

C 

H 

+ 

CH 3 

Racemic mixture 

Saturated carbon means its geometry is tetrahedral, for carbocation the geometry is 

planar. The starting compound is a asymmetric compound but the carbocation i.e., symmetric to 

the product is always racemic mixture. 

Eg: SN 2 reaction: 

Kinetic observed is second order. 

b 

a 

c 

b 

a 

d d slow 

d d 

C x y C x 

d 

Transition state 

y 

Br 

OH 

C 

b 

d 

a 

Inversion 

configuration 

The nucleophilic attack takes place from the side remote to that of the leaving group. 

The transition state is also the asymmetric compound. The reaction with the formation of 

the transition state is always leads to the product i.e., leads to inversion of configuration. By 

using polarimeter the optical activity is measured. 



23


* Described that the kinetic and thermodynamic control of a reactions and microscopic 

reversibility 

* Explained the aromaticity of benzenoid and heterocyclic compounds 

* Discussed the Hammond’s postulate, primary and secondary kinetic isotopic effect 

* Pointed out the identification of product and intermediate, isotropic labeling and stereo 

chemical evidences 


1. What is isotopic effect? How does isotopic labeling help in establishing the mechanism of 

a reaction? 

2. Discuss the importance of kinetic evidence in establishing the mechanism of a reaction. 


1. State Hammond’s postulate. Explain with a suitable example the application of 

Hammond’s postulate in determining the shape and geometry of transition state. 

2. Explain non-kinetic methods of study of reaction mechanism. 





24


LESSON: 3 – LINEAR FREE ENERGY RELATIONSHIP 

CONTENTS 



3.2. THE HAMMETT EQUATION 






The aim is to motivate and enable a broad knowledge on linear free energy relationship to 

the students. 


* Understood the linear free energy relationship. 


For the study of reaction mechanism, one has to collect several evidences which point to 

the mechanism of the reaction. An important concept is that a given structural feature will effect 

related reactions in generally the same way. Thus if replacement of a hydrogen by chlorine 

makes acetic acid to become a strong acid, then introduction of a chlorine at the a-position of 

propanoic acid will also result in an increase in acidity. A linear free energy relationship is 

simply a quantization of this concept. 

3.2. THE HAMMETT EQUATION 

The first and most important linear free energy relationship is the Hammett sr equation 

which is based on the acidities of aromatic carboxylic acids. 

Acidities of benzoic and phenylacetic acids were measured by changing substituent group 

on the aromatic ring. In these experiments the positions of acid base equilibria were measured as 

functions of the substituent groups. In case the different acidity values for each series of 

compounds are due only to the influence of the substituents, then a relation between the sets of 

data should exist. When the pKa values obtained from the two series of compounds were plotted 

against each other (Fig. I), a linear relation (Equation I) was obtained. 

25


Fig. I. Hammett plot. 

[Fig. I. is a Hammett plot with r = 0.46. The value of r indicates the sensitivity of a 

reaction or equilibrium to particular substituents. A positive r-value shows that the reaction or 

equilibrium is aided by electron attracting substituents (withdrawl of electrons from the reaction 

site). In case of phenylacetic acids, for ionization, the r of + 0.46 points that a given electron 

attracting substituent facilitates ionization but has only 0.46 of the effect that the same substituent 

has in facilitating ionization of benzoic acid] 

The pKa values for phenylacetic and benzoic acids 

pKPA = r(pKB) + C ------ (I) 

r (rho) = a proportionality constant – is the slope of the line (or) 

log KPA = r log KB + C’ 

C or C’ = the intercept of the straight line. 

The acidity values of un-substituted carboxylic acids pK0 (substituent = H) are taken as 

standards with which the effect of a substituent is compared and the equation II is for this 

standard. An expression III is obtained on subtracting one equation from the other, and this 

expression relates the substituent effects on the two series of compounds (the K and K0 represent 

the equilibrium constants for substituted and un-substituted compounds. 

log KoPA = r log K0B + C’ ------ (II) 

K 

K 

PA 

B 

log = r log 

------ (III) 

0PA 

K 

K 

0B 

The acidities of different benzoic acids in equation media (25°C) are the standard 

measure of the effect of each substituent group and the substituent constant sigma (s) for every 

substituent group is defined in the expression IV. The Hammett equation-the linear relation is 

thus expressed as in equation V. Sigma (s), the substituent constant is a measure of the effect of a 

substituent on the acidity of benzoic acid. Those substituents which enhance the acidity relative 

26


to unsaturated benzoic acid will show positive values (s > 0), the hydrogen atom having a sigma 

value of zero. 

K 

K 

B s = log 

------ (IV) (s - substituent constant) 

0B 

K PA log = sr 

------ (V) 

K 

0PA 

The Hammett equation can thus be used: 

1. To account for the influence of substituents on molecular reactivity. 

2. It explains the influence of polar meta- or para-substituents on the side chain reactions of 

benzene derivatives. Table.1. summarizes s values for different meta and para 

substituents. The s constant is generally independent of the nature of the reaction by m-or 

p-substituent relative to hydrogen. A negative s value signifies an electron attracting 

group. The large the magnitude of s, the greater is the effect of the substituent. The r 

constant (r is the reaction constant) is dependent on the nature of the reaction and on 

conditions. It is a measure of the sensitivity of a given reaction series to the polar effect of 

ring substituents i.e., to changes in the s values of the substituent. 

Substituent 

NH2 

CH3 

OH 

C6H5 

OCH3 

SCH3 

F 

I 

Cl 

Br 

CF3 

CN 

NO2 

Table. 1. Hammett substituent constant values of common groups. 

sm 

-0.16 

-0.07 

0.12 

0.06 

0.12 

0.15 

0.34 

0.35 

0.37 

0.39 

0.43 

0.56 

0.71 

3. Reactions that are assisted by high electron density at the reaction site have negative r 

values. 

4. The Hammett equation is however, not applicable to the influence of ortho substituents, 

since these exert steric effects. 

When one considers the rates of hydrolysis of substituted benzoates with hydroxide ion 

(in aqueous acetone), one observes a straight line on plotting against the Hammett s-constants 

with a slope (r) of 2.23. These data show that the substituent groups which facilitate ionization of 

sp 

-0.66 

-0.17 

-0.37 

-0.01 

-0.27 

-0.0 

0.06 

0.18 

0.23 

0.23 

0.54 

0.66 

0.78 

27


benzoic acid, facilitate the hydrolysis of benzoate as well. For ester hydrolysis the transition state 

(Scheme I, the reaction involves nucleophilic attack by the hydroxide ion on the carbon atom of 

the carbonyl group), has considerable negative charge, since positive r indicates stabilization by 

electron attracting group. Indeed, in keeping with this observation the mechanism of ester 

hydrolysis which proceeds through an anionic tetrahedral intermediate gets support. Moreover, 

this hydrolysis will be further facilitated when electron withdrawing group (s is positive, Table. 

1) is attached to the aromatic ring. With an electron releasing group (s is negative) the reaction 

will be retarted. 

O O- 

= 

Ar-COCH 3 + OH Ar -C-OH ArCO 2 

- 

OCH 3 

Scheme I 

28 

+ CH 3OH 

Hydration of styrenes (HClO4, 25°C) shows a –r value, to show that the transition state of 

the reaction is like a carbocation intermediate. 



* Explained the Hammett equation 


1. What is Hammett constant s ? Predict the sign of Hammett s constant for the following 

substituents giving a proper reason: m-NO2, p-MeO, p-CO2H, m-OH, and p-OH. 

2. Predict the sign of r for the following reactions. 

(a) ArH NO2 ArNO2 H 

(b) 


ArCOCl EtOH ArCO 2Et HCl 

1. Derive Hammett equation and explain its applications. 

2. Explain quantitative treatment of the effect of structure on reactivity (Using LFER). 




international publishers.


UNIT-II 

LESSON: 4 – AROMATIC ELECTROPHILIC SUBSTITUTION 

REACTIONS 

CONTENTS 



4.1.1. MECHANISM OF ELECTROPHILIC SUBSTITUTION 

4.2. NITRATION 

4.3. SULPHONATION 

4.4. HALOGENATION 

4.5. FRIEDEL CRAFTS REACTIONS 

4.5.1. ALKYLATION 

4.5.2. ACYLATION 

4.5.3. APPLICATIONS 






The aim is to motivate and enable the student to comprehend the possible chemical route 

by which the aromatic electrophilic substitution reactions may proceed. 


* learnt possible reaction pathways in aromatic electrophilic substitution reactions. 


The benzene is a resonance hybrid which is a flat ring with a cyclic cloud of negative 

charge above and below the plane of the ring. Benzene ring therefore discourages nucleophilic 

attack and encourages electrophilic attack only. 

+ E 

+ H 

The typical reaction of benzene and its derivations are electrophilic substitution. Aromatic 

electrophilic substitution includes a wide variety of reactions such as nitration, sulphonation, 

halogenation, Friedel-crafts reactions etc. the reaction permits the direct introduction of groups to 

the ring and their subsequent transformation to various products. 

E 

29


H SO 

ArH + HNO ¾¾ 

2¾ 

¾4 

® ArNO + H O 

3 

2 2 

AlCl 

ArH + Cl ¾¾ 

¾ 

3® 

ArCl + HCl 

2 

SO 

ArH + H SO ¾¾ 

¾3 

® ArSO H + H O 

2 4 

3 2 

AlCl 

ArH + RCl ¾¾ 

¾ 

3 ® ArR + HCl 

4.1.1. MECHANISM OF ELECTROPHILIC SUBSTITUTION 

The reagent and catalyst undergo acid-base reaction to produce the attacking electrophilic 

which then attacks the ring to form a carbocation (s complex) in the first slow step. In the 

second step the proton from the site of attack is rapidly removed by the base to complete the 

reaction. 

+ 

- 

E - Nu + cat ® E + Nu - cat 

------ (i) 

E 

H 

+ Cat-Nu 

Slow 

+ E 

H 

Fast 

s - complex 

E 

E 

30 

+ HNu + Cat (ii) 

The energy gained in passing from the s complex to the product provides the energy for 

breaking the strong C - H bond. It may be seen that the formation of s complex would involve 

high energy. This is however, not so because the energy liberated by the formation of C - E bond 

and the delocalization of the positive charge lowers the energy of the s complex. 

The rate of reaction does not involve the breaking of the C - H bond. This has been 

established by isotope effect. The rates of reaction are the same on replacement of hydrogen by 

deuterium or tritium. Hence, the rate of the substitution reaction is determined by the slow 

attachment of the electrophile to the ring in the first step. 

4.2. NITRATION 

Nitration of benzene is effected with a mixture of concentrated nitric and sulphuric acids. 

H acts as a strong 

In the absence of sulphuric acid the reaction is slow. It is suggested that 2SO4 

acid protonates. 3 

methods. 

HNO to generate nitronium ion, 2 O N+ 

.This has been confirmed by various


HO - NO 2 + H 2SO 4 H 2O -NO 2+ HSO 4 - H 2SO 4 

Overall reaction is 

HNO 3 + 2H 2SO 4 

NO 2 + 2HSO 4 - + H3O + 

The nitronium ion then attacks the benzene ring to form a carbocation in the first step. 

+ 

NO 2 

NO 2 

Slow H 

H 

NO 2 

H 

NO 2 

31 

HNO 3 + H 2SO 4 

In the second step, a fast abstraction of hydrogen from the site of attack by the base 

( HSO4 - ) completes the reaction. 

H 

NO 2 

+ HSO 4 

Fast 

NO2 + 

H 

NO 2 

H 2SO 4 

The presence of appreciable amount of water in the acid mixture is not desirable since it 

reduces the nitronium ion, hence the use of concentrated acid mixture. 

NO2 + H + 

2O H2NO3 HSO4 - 

+ 

H 3O + +NO 2 + +2HSO4 - 

Phenol, which is highly reactive due to the mesomeric effect of the OH group, is nitrated 

even with dilute HNO 3 . A small amount of phenol is oxidized to produce HNO2 which with 

+ 

HNO3 gives nitrosonium ion, NO . The latter nitrosates the reactive phenol to yield nitrosophenol 

which is rapidly oxidized to nitrophenol with HNO3 and nitrous acid is produced by reaction of 

HNO3. With the progress of the reaction more and more nitrous acid is produced and the reaction 

rate is increased. 

HNO 2 + 2HNO 3 

H 3O + + 2NO 3 - + NO +


OH 

NO + 

4.3. SULPHONATION 

OH 

H NO 

NO 3 - 

OH 

NO 

HNO 3 

OH 

NO 2 

p-nitrosophenol p-nitrophenol 

32 

+ HNO 2 

Benzene on heating with concentrated or better with fuming sulphuric acid gives benzene 

sulphonic acid, C6 H 6SO3H 

. Sulphonation can also be affected withClSO3 H . 

C6H6 + H2SO4 C6H5SO3H + H2O The reaction is slow with conc. 2SO4 

electrophile is 3 

ring. 

- 

H 

Slow 

H but rapid with oleum or 3 

H 2SO . 

SO which is present in small amount in 4 

2H2SO4 SO3 + HSO4 + H3O SO in inert solvent. The 

The electrophile SO 3 is neutral but has powerful electrophilic sulphur which attacks the 

SO 3 - 

H 

+ SO3 H 

H 

SO 3H 

SO 3H 

The rate determining step involves the breaking of C - H bond. Since deuterated 

benzene is sulphonated more slowly. The reaction is reversible on treatment with steam. 

H group is replaced by hydrogen. The reversibility of the reaction has practical utility. 

SO 3 

4.4. HALOGENATION 

Free halogens can attack activated benzene rings but lewis acid catalyst is required for 

benzene ring. It is suggested that probably benzene first forms a p complex with the halogen


molecule. (Eg) Br 2 . The lewis acid ( FeBr3 ) then polarizes the Br - Br bond and helps in the 

formation of a s complex between benzene carbon and the electrophilic end of the polarized 

bromine by removing the incipient bromide ion. Subsequent abstraction of hydrogen in the 

second step completes the reaction. 

+ Br 2 

Br 

H 

d + d - 

Br-Br Br.....Br.....FeBr 3 

p - complex 

+ FeBr 4 Br + HBr + FeBr 3 

The order of reactivity of the halogen is F 2 > Cl2 

> Br2 

> I 2 . Fluorine is too reactive for 

practical use. Under ordinary condition, ionization fails. In the presence of HNO 3 direct 

+ 

iodination has been affected. The attacking electrophile I is produced by HNO 3 . 

4.5. FRIEDEL CRAFTS REACTIONS 

Alkylation and acylation of aromatic rings with alkyl halides and acid chlorides or 

anhydrides respectively in the presence of lewis acids, E.g. AlCl 3 , FeBr3 

, BF3 

, BCl3 

, etc is known 

as friedel crafts reaction. 

4.5.1. ALKYLATION 

COR 

RCOCl 

AlCl 3 

RCl 

AlCl 3 

The function of the catalyst is to provide a real or potential carbocation for the 

electrophilic attack. When the alkyl group can form a stable carbocation as in the case of tertiary 

halides, the attacking species is the real carbocation which forms as ion pair. 

Me 3CAlBr 4 

Me 3CBr + AlBr 3 

H 

CMe 3 

(1) 

AlBr 4 

Me 3C + Al - Br 4 

- HBr 

- AlBr 3 

33 

R 

CMe 3


In other cases a polarized complex with a potential carbocation is the attacking species. 

- 

- 

HCl 

AlCl 3 

R-Cl + AlCl 3 

d 

+ R-----Cl-----AlCl 3 

- 

d + 

R 

(2) 

d 

R-----Cl-----AlCl 3 

- 

d + 

H 

R 

AlCl 4 

The intermediates (1) and (2) have been isolated in some cases. It has been observed that the sane 

alkyl halide gives a rearranged and unrearranged product with different lewis acid catalysts. 

C 6H 6 + Me 3C.CH 2Cl 

C 6H 6 + Me 3C.CH 2Cl 

AlCl 3 

FeCl 3 

C 6H 5CMe 2CH 2Me 

Rearranged 

C 6H 5CH 2CMe 3 

Unrearranged 

Since AlCl 3 is a stronger lewis acid than ( FeCl 3) 

. It is presumed that the complex with 

AlCl 3 is so strongly polarized that the alkyl group attains almost a free carbocation character to 

undergo rearrangement. The alkylating reagent besides alkyl halides may be aliphatic alcohols, 

alkenes, ethers, etc in the presence of strong proton acids which generate the carbocation for the 

electrophilic attack. 

4.5.2. ACYLATION 

Acylating reagents are acid chlorides or acid anhydrides in the presence of lewis acid. 

The electrophilic species may be (a) acylcation as an ion pair or (b) a polarized 1:1 complex. 

Probably both mechanisms operate depending on conditions. 

(i) 

RCOCl + AlCl3 RCO + AlCl4 or RCOAlCl 4 

Ion pair 

34


(ii) 

RCOAlCl 4 

RCOCl + AlCl 3 

- HCl 

- AlCl3 + 

d + 

RC=O 

H 

COR 

d + 

AlCl 4 

- HCl 

- AlCl3 d - 

R C O ----- AlCl3 d - 

R C O ----- AlCl3 Cl 

Cl 

1:1 complex 

H 

d + 

C 

Cl 

d - 

O ----- AlCl3 COR 

In both cases, one mole of the catalyst remains complexed with the product, ketone. 

Hence slightly more than one mole of lewis acid is required for acylation. Acylation may be 

affected with acid anhydride also. The attacking species in this case may be a free 

+ 

RCO or RCOCl . 

4.5.3. APPLICATIONS 

The reaction is very useful for the synthesis of many classes of organic compounds. 

(a). Hydrocarbons: 

(b). Ketones: 

C 6H 6 + C 6H 5CH 2Cl 

C 6H 6 + RCOCl 

(c). Poly-nuclear hydrocarbons: 

AlCl 3 

AlCl 3 

PhNO 2 

C 6H 5CH 2C 6H 5 

Diphenyl methane 

C 6H 5COR + HCl 

35



CH 2-CH 2-CH 2-CH 2-Cl 

AlCl 3 

Tetralin 


* Pointed out the mechanism of electrophilic substitution such as nitration, sulphonation, 

halogenation, Friedel crafts reactions (alkylation and acylation) and its applications 


1. It is known that the aromatic electrophilic substitution is a two step process. What are the 

arguments which can be advanced in support of this statement? 

2. Name the electrophile and show with the chemical equation how it is produced in the 

reaction, bromination with bromine in presence of FeBr3. 


1. Give the mechanism for following reactions. 

(a) Nitration 

(b) Sulphonation 

2. Differentiate Friedel Craft Alkylation and Acylation with mechanism and applications. 





36


LESSON: 5 - ORIENTATION AND REACTIVITY: ELECTOPHILIC 

SUBSTITUTION ON MONOSUBSTITUTED AND DISUBSTITUTED 

BENZENES 

CONTENTS 



5.2. ELECTOPHILIC SUBSTITUTION ON MONOSUBSTITUTED BENZENES 

5.2.1. ACTIVATION AND DEACTIVATION 

5.3. ELECTROPHILIC SUBSTITUTION OF DISUBSTITUTED BENZENES 






The aim is to motivate and enable a comprehensive knowledge on orientation and 

reactivity of electophilic substitution on monosubstituted and disubstituted benzenes to the 

students. 


* Understood the orientation and reactivity of electophilic substitution on monosubstituted 

and disubstituted benzenes. 


Since each product i.e. ortho, para or meta originates from the same starting materials, 

the partitioning to different products must relate to the relative activation energies of each 

reaction. Although the cyclohexadienyl cation produced in each case is stabilized by resonance, 

there are important differences. An analysis of these differences helps to explain the orientation. 

It must be remembered that a more stable intermediate is associated with a more stable transition 

state and lower activation energy in the rate determining step. The more stable a reaction 

intermediate, the greater is the proportion of product derived from that intermediate. As an 

example electrophilic substitution on toluene may be considered eg. Nitration of toluene gives 

essentially ortho and para substitution products as the major product and only 4% of the meta 

product. 

37


CH 3 

HNO 3 / H 2SO 4 

30 ° 

CH 3 

o-Nitrotoluene 

(59%) 

NO 2 

+ 

CH 3 

NO 2 

p-Nitrotoluene 

(37%) 

+ 

CH 3 

m-Nitrotoluene 

(4%) 

Compare the carbocations formed by the attack of the electrophile (E + ) at the ortho, para 

and meta position of toluene. Reaction at the ortho and para positions gives two of the structures, 

in each case, which are those of secondary carbocation, but the third structure corresponds to a 

more stable tertiary carbocation. Although, the methyl group releases electrons to all the position 

in the ring, it does so more effectively to the carbon atom nearest to it. Therefore structures 

(I and II) are particularly more stable and because of contributions from these structures ,the 

hybrid carbocation as a result of attack at the ortho and para positions is more stable than the 

carbocation resulting from the attack at the meta position. The sigma complex for the ortho and 

para substitution has its positive charge spread over two 2° carbons and one 3° carbon. When 

substitution occurs at the meta position the positive charge is not delocalized onto the tertiary 

carbon. As a consequence, the methyl group has a much smaller effect on the stability of the 

sigma complex. 

CH 3 

H 

H C H 

E + 

( I ) 

H 

E 

E 

H 

H 

C H 

H 

H 

H 

C H 

Ortho attack 

E 

H 

H C H 

E 

H 

Para attack ( II ) 

H 

H 

H 

C H 

E 

H 

H 

E 

H 

38 

NO 2 

C H 

H


H 

H 

C H 

E 

H 

Meta attack 

H 

H 

C H 

E 

H 

H 

H 

C H 

In summary, therefore, an alkyl group stabilizes the sigma complexes and the transition 

states leading to these. This stabilization is, however, most effective when the alkyl group is 

ortho (or) para to the site of substitution. Steric factors may be involved in the attacking 

electrophile. Thus, the chlorination to chlorobenzene (Cl + is the electrophile) gives a mixture of 

dichlorobenzenes in which the ortho/para ratio is about 0.7 whereas nitration of chlorobenzene 

(the electrophile is the more bulky nitronium ion, NO2 + ) gives an ortho/para ration of about 0.4. 

The net result is, therefore, ortho and para orientation. 

5.2. ELECTOPHILIC SUBSTITUTION ON MONOSUBSTITUTED BENZENES – 

ORIENTATION AND REACTIVITY 

The reactivity of mono-substituted benzene (C6H5-S) and the orientation of incoming 

substituent depend on the nature of the substituent (S) already present on the ring. A monosubstituted 

benzene on electrophilic substitution may give three possible di-substituted products 

(ortho, meta and para isomers). 

From the yields of these isomers, it is possible to separate the substituents into two groups 

the o, p-directors which give predominantly o, p products and the m-directors which mainly give 

mainly the meta products. 

The following points will help to understand both the reactivity i.e., if the reaction will be 

slower or faster than with benzene and orientation of the incoming group in a mono-substituted 

benzene derivative, i.e., the position (o, p or m) which the new group will take. 

5.2.1. ACTIVATION AND DEACTIVATION 

The term activation or deactivation is applied when the reactivity of mono-substituted 

benzene (C6H5-S) in electrophilic substitution reaction is compared with benzene (C6H6) under 

the identical conditions. An electron-releasing group i.e., +I effect of the substituent helps to 

E 

H 

39


Reaction 

is 

faster 

E 

S releases 

electrons 

S 

H 

E 

H 

H 

E 

S withdraws 

electrons 

S 

H 

Reaction 

is 

slower 

Arenium ion 

Standard 

Arenium ion 

is stabilised 

is destabilised 

stabilize the positive charge of the reaction intermediate (s complex) produced in the ratedetermining 

step by furthering the delocalization of the charge. This will serve to lower the 

activation energy in the rate determining step relative to that of benzene. Thus, the compound 

(C6H5-S) where S has +I effect will undergo electrophilic substitution reactions more readily than 

benzene itself (i.e., faster rate or milder conditions). Such a group is said to be an activating group 

(Table II.5.1). 

Table II.5.1. 

Substituents Reactivity Orientation 

-NR 2, -NH 2, -OH, -O 

O 

O 

-N C R, -O C R, -OR 

-R,-Ar 

-H 

-X , -CH 2X 

-NO 2,-SO 3H,-C=O, 

C N,-NR 3,-SR 2,-CF 3 

Strongly activating 

Activating 

Weakly activating 

(Standard for comparision) 

Weakly deactivating 

Strongly deactivating META DIRECTORS 

Effect of substituents on electrophilic aromatic substitution 

40 

ORTHO- PARA 

DIRECTORS


On the other hand, an electron-withdrawing group, (-I effect) will exert the opposite 

effect. It destabilizes the positive charge of the reaction intermediate (the s complex) in the rate 

determining step by developing electron density away from the ring, thus intensifying the 

positive character of the ring carbons compared with benzene to raise the activation energy of its 

rate-determining step, thus rendering the compound C6H5-S less reactive than benzene in 

electrophilic substitution reactions. Such a group is called a deactivating group (Table II.5.1), and 

an example is of -N + Me3 group which with its –I effect is deactivating. 

A substituent however, releases electron density to the aromatic ring or depletes electron 

density from it via both inductive (I) and resonance (R) effects. This is explained by taking, 

phenol, toluene, chlorobenzene and an aryl ketone as examples. 

(i). Phenol: The OH group is activating +R effect > -I effect. Electrons are therefore, released 

from this group into the ring making the ring positions in phenol more electron-rich than those of 

(o and p) benzene (Fig) it, therefore, is more susceptible to electrophilic attack than benzene. 

OH 

The -I effect 

OH OH OH 

a +R effect 

(ii). Toluene: The CH3 group is activating +I and +R effects (caused by hyperconjugation) work 

together to push electron density into the ring (Fig) and like phenol, therefore, toluene is more 

susceptible to electrophilic attack than benzene. 

H 

H C H 

a +I effect 

H 

H 

C 

H 

H 

H 

C 

+R effect (hyperconjugation) 

H 

H H C 

(iii). Chlorobenzene: The Cl atom on the other hand is deactivating because –I effect > +R 

effect. There is a slight drain of electron density away from the ring positions of this compound 

so that they are comparatively less electron-rich than those of benzene (Fig). The compound thus 

is less susceptible electrophilic attack than benzene. 

41 

H


Cl 

a -I effect 

Cl Cl Cl 

the +R effect 

(iv). Aryl-ketones: The RCO-group is deactivating, since –I effect and –R effect now work hand 

in hand together to draw electron density away from the ring, to make ring positions less 

electron-rich compared to those of benzene. The compound is, thus, less susceptible to 

electrophilic attack than benzene. 

R 

d 

C 

-I effect 

d 

O 

R O 

C 

R O 

C 

-R effect 

42 

R O 

C 

(v). Summary: Substituents with –I and –R effects e.g., NO2, COR, CO2R, CN are deactivating 

and meta directing, however, their deactivating influence is less than the positively charged 

–N + Me3 group. 

Substituents with +I and +R effects like alkyl groups are activating and ortho, paradirecting. 

The –O - substituent e.g., in a phenoxide ion ArO - , is also of +I and +R type and these 

effects are much stronger compared with those in an alkyl group. For this reason, the phenoxide 

ions are even more reactive toward electrophilic substitution than are phenols themselves. Thus 

the weak electrophiles like phenols in electrophilic aromatic substitution (a diazo coupling 

reaction). The diazo coupling with phenols occurs most readily in slightly alkaline solution, when 

an appreciable amount of the phenol is present as its more reactive phenoxide ion. In case the 

p-position is not open then coupling takes place in the o-position as is so in 4-methylphenol 

(p-cresol).


[C 6H 5N N] Cl 

Arenediazonium ions 

are weeak electrophiles 

+ 

OH 

is present as a phenoxide ion 

NaOH 

N N 

H 

- H 

43 

OH 

N N OH 

An azo compound 

(p-hydroxyazobenzene) 

5.3. ELECTROPHILIC SUBSTITUTION OF DISUBSTITUTED BENZENES 

Aromatic substitution reactions of disubstituted benzenes usually lead to a mixture of 

products because of competing orientation influences of two substituents to afford a mixture of 

products. If both substituents are activating groups, the position of the incoming electrophile is 

primarily governed by the orientation influence of the stronger of the two activating groups. If 

one substituent is activating while the other is deactivating, the position of the entering group will 

be dictated mainly by the activating group (FIG). The position between the two meta substituents 

is least attacked by the incoming electrophile due to the steric hindrance. 

OCH 3 

CH 3 

OCH 3 

CH 3 

OCH 3 

CH 3


CH 3 


NO 2 


* Pointed out the orientation and reactivity of electophilic substitution on monosubstituted 

and disubstituted benzenes 


CH 3 

NO 2 

CH 3 

NO 2 

1. Explain the effect of substituents on electrophilic aromatic substitution reactions. 

2. Explain the electrophilic substitution of disubstituted benzene. 


1. Briefly explain the theory of orientation in electrophilic aromatic substitution. 

2. “A substituent releases or depletes electron density to the aromatic ring”. Explain the 

statement with examples. 





44


LESSON: 6 – TYPICAL AROMATIC ELECTROPHILIC SUBSTITUTION 

REACTIONS 

CONTENTS 


6.1. GATTERMAN REACTION 

6.2. GATTERMANN-KOCH REACTION 

6.3. THE REIMER-TIEMANN REACTION 

6.4. KOLBE REACTION 

6.5. HOFFMANN-MARITUS REACTION 

6.6. JACOBSEN REACTION 


6.8. LESSON END ACTIVITIES 





by which the aromatic electrophilic substitution reactions may proceed. 


* learnt possible reaction pathways in typical aromatic electrophilic substitution reactions. 

6.1. GATTERMAN REACTION 

ArH 

+ 

Zn(CN) 2 

HCl 

ArCH NH 2 Cl 

H 2O 

ArCHO 

Formylation with ( Zn ( CN) 

2 ) and HCl is called the Gattermann reaction. In contrast to 

reaction this method can be successfully applied to phenols and their ethers and to many 

heterocyclic compounds. However it cannot be applied to aromatic amines. In the original 

version of this reaction the substrate was treated with HCl, HCN, 

ZnCl2 

but the use of 

( Zn ( CN) 

2 ) and HCl makes the reaction more convenient to carry out and does not reduce 

yields. The mechanism of the Gattermann reaction has not been investigated very much, but there 

is an initial nitrogen containing product that is normally not isolated but is hydrolyzed to 

aldehyde. 

ArH + ZnCl 2(RCN) 2 + HCl 

Ar C R Ar C R 

NH 2 Cl 

The first stage consists of an attack on the substrate by species containing the nitrile and 

HCl to give an imine salt. In the second stage the salts are hydrolyzed to the products. 

O 

45


6.2. GATTERMANN-KOCH REACTION 

The formylation of benzene and alkylbenzene using carbonmonoxide and hydrogen 

chloride in the presence of aluminium chloride (catalyst) and a small amount of cuprous chloride 

(co-catalyst) under high pressure is known as Gattermann-Koch reaction. 

Benzene 

+ CO + HCl 

AlCl 3 

Cu 2Cl 2 

Benzaldehyde 

Usually, nitrobenzene or ether is used as solvent. In the case of alkylbenzene, the 

aldehyde group is introduced into the para position only. This method is used industrially to 

prepare arylaldehdes. 

H 3C 

Toulene 

+ CO + HCl 

AlCl 3 

CH 3Cl 2 

H 3C 

CHO 

p-tolualdehyde 

-50% 

The Gattermann-Koch aldehyde synthesis is not applicable to phenols o their ethers, 

amino aromatic species and also when the aromatic ring is strongly deactivated. (Nitrobenzene) 

Mechanism: 

The Gattermann-Koch formylation is considered as a typical electrophilic aromatic 

substitution with high para regioselectivity. The most likely electrophile is the acylium ion 

+ + 

+ 

- 

[HCO ] in the ion pair[ 

HCO ] [ AlCl4 

] . Common factors such as electron density of the 

aromatic substrate, reactivity of electrophile, stability of reaction intermediates, and steric factors 

may influence the regioselectivity. 

C - 

: 

_ 

Cl 

+ 

: C O .. 

AlCl 3 

O C O C O 

_ 

AlCl3 Cl 

+ 

H 

+ 

C_ O .. 

AlCl 3 

_ 

AlCl3 HCl 

CHO 

46


+ O 

Cl H 

Application: 

_ 

AlCl3 + 

CH 3 

1-Methyl naphthalene 

O 

C 

H 

_ 

Cl 3Al 

Co+HCl 

H 

conventional 

type 

SbF 3-HF/Co 

or 

F 3COOH-SbF 5/CO 

Modified process 

6.3. THE REIMER-TIEMANN REACTION 

: O : 

+ 

Cl H 

s - complex 

CHO 

aromatization 

CH 3 

CHO 

+ 

CH 3 

CHO 

H C O 

Acylium ion 

CHO 

47 

AlCl 4 

+ HCl + AlCl3 CH 3 

CHO 

The formylation of activated aromatic ring compound with chloroform in alkaline 

solution is known as Reimer-Tiemann reaction. The method is useful only for phenols and 

certain heterocyclic compounds such as pyrroles and indoles. It leads preferentially to the 

formation of an ortho formylated product; when both the ortho positions are blocked, the 

incoming group occupies the para position.


_ 

O 

OH 

+ 

_ 

O 

+ 

CHCl 3 

OCH 3 

CHCl 3 

(i)NaOH 

(i i)Hydrolysis 

+ CHCl 3 

(i)NaOH 


OH 

Sal icylaldehye 

(major) 

(i)NaOH60C ° 


OH 

Sal icylaldehye 

CHO 

+ 

OH 

CHO 

CHO 

Vani l l in 

OH 

CHO 

OCH 3 

The Riemer-Tiemann reaction is mainly used for the synthesis of ortho-hydroxy aromatic 

aldehydes. Yields are generally low. However it has been reported that application of ultrasound 

leads to shorter reaction times and improved yields. If CCl4 is used instead ofCHCl 3 , 

carboxylation occurs under the reaction conditions. 

48


Mechanism 

OH 

Phenol 

CCl 4 + KOH 

OH 

Sal icyl ic acid 

COOH 

The reaction is believed to proceed in the following manner. Firstly the dichlorocarbene 

(: CCl 2 ) an electron-deficient reactive species is formed by the reaction of chloroform with 

strong alkali. In the second step, it attacks the electron rich ortho position of the aromatic ring to 

form orhtodichloromethylphenolate, which hydolysis to give hydroxyarylaldehyde. 

_ 

HO 

OH 

H 

_ 

OH 

_ 

H2O C 

Cl 

Cl 

_ 

O 

Cl 

C 

_ 

H 2O 

:CCl 2 

Cl 

_ 

_ _ 

Cl 

: C Cl 

Cl 

Nucleophi l ic attack of aromatic ring 

to the electron-def icient species on 

the ortho position 

- 

O H 

O H 

_ 

_ 

Cl 

Cl 

Cl 

O 

Cl 

H 

_ 

OH 

49 

:CCl 2 

_ 

CCl 2


- 

O 

H 

OH 

Cl 

_ 

_ 

Cl 

O 

The involvement of dichlorocarbene as the reaction intermediate receives support from 

the fact that certain substrates (Eg) pyrrole under the reaction condition gave side products 

(called as abnormal product) along with the normal products or instead of these. 

KOH 

Application 

N 

H 

:CCl2 Diclorocarbene 

intermediate 

N .. 

CHCl 3 

KOH 

Cl 

Cl 

N 

H 

H 

CHO 

O 

+ 

Normal product Abnormal product 

H 

N 

_ 

Cl 

Cl 

_ 

OH 

Ring expansion 

The reaction offers a useful method for introducing formyl group in phenolic compound 

as well as certain heterocycles. For (Eg). 

50 

CHO


N 

H 

6.4. KOLBE REACTION 

Decarboxylative dimerization 

OH 

2RCOO 

CHCl 3/KOH 

Hydrolysis 

(i) 

CHCl 3/KOH 

Hydrolysis 

(ii) 

Electrol 

R 

R 

N 

H 

CHO 

Electrolysis of carboxylate ions, which results in decarboxylation and combination of the 

resulting radicals, is called the Kolbe reaction. it is used to prepare symmetrical R - R where R 

is straight or branched chained, except that little or no yield is obtained when there is 

a branching. when R is aryl , the reaction fails. Many functional groups may be present, though 

many others inhibit the reaction. Unsymmetrical R - R¢ 

have been made by coupling mixtures of 

acid salts. A free radical mechanism is involved. 

Mechanism 

O 

_ 

R O 

RCOO 

Electrolytic 

Oxidation 

- e 

Electrolytic 

Oxidation 

O 

. 

R O 

. 

RCOO 

-CO 2 

-CO 2 

R 

. Radical 

R 

Combinaion 

R 

CHO 

R 

OH 

51 

R


6.5. HOFFMANN-MARITUS REACTION 

When HCl salts of aryl alkyl amines are heated at about 200 to 300 migration occurs. 

This is called the Hofmann- Maritus reaction. it is an intermolecular reaction, since crossing is 

found. For example methyl anilinium bromide gave not only the normal products o and 

p-toluidine but also aniline and di and trimethylanilines. As would be expected for an 

intermolecular process, there is ionization when R is primary. With primary R , the reaction 

probably goes through the alkyl halide formed initially in an SN2 reaction. 

H 

R + H Cl 

N 

HCl 

NH 2 

RNH2Ar + Cl RCl + ArNH2 Evidence for this view is that alkyl halides have been isolated from the reaction mixture 

- - - 

and that Br , Cl , I gave different ortho/para ratios, which indicates that the halogen is involved 

in the reaction. Further evidence is that the alkyl halides isolated are rearranged even though the 

alkyl groups in the ring are rearranged. Once the alkyl halides are formed, it reacts with the 

substrate by a normal friedel-crafts Alkylation process, accounting for the rearrangement. When 

R is secondary or tertiary carbocation may be directly formed so that the reaction does not go 

through the alkyl halides. 

6.6. JACOBSEN REACTION 

When polyalkyl or polyhalobenzenes are treated with sulphuric acid, the ring is 

sulphonated, but rearrangement also takes place. The reaction, known as Jacobsen reaction, is 

limited to benzene rings that have at least four substituents, which may be any combination of 

alkyl and halogen groups, where the alkyl groups may be ethyl or methyl and the halogen iodo, 

chloro, bromo. When isopropyl or t-butyl groups are on the ring, these groups are cleaved to give 

olefins. Since a sulpho group can later be removed. The Jacobsen reaction can be used as a 

means of rearranging polyalkylbenzenes. The rearrangement always brings the alkyl or halo 

R 

52


H 3C 

CH 3 

H 3C CH 3 

H 2SO 4 

H 3C 

H 3C 

SO 3H 

groups closer together than they were originally. Side products in the case illustrated above are 

pentamethylbenzenesulphonic acid, 2, 4, 5 trimethyl benzenesulphonic acid, etc., indicating an 

intermolecular process, at least partially. 

The mechanism of the Jacobsen reaction is not established, but a likely possibility or 

attack by a sulphonating species at an ipso position .with the alkyl group thus freed migrating 

inter or intramolecularly by another position. 

+ 

H 2S 2O 7 

or 

H 3SO 4 

HSO 4 

(b) 

SO 3H 

H 

HSO 4 

(a) 

CH 3 

CH 3 

SO 3 

- 

SO3H SO3 Path ‘a’ is the principal route, except at very high H 2SO4 

concentrations, when path ‘b’ 

+ 

becomes important. With H the first step is rate determining under all conditions, but in 

3 4 SO 

2 2 7 O S H the first step is the flow step only upto about 96% 4 

transfer becomes partially rate determining step. 



H 

H 2SO , when a subsequent proton 

Ø pointed out the typical aromatic electrophilic substitution reactions such as 

Ø Gattermann reaction 

Ø Gattermann-Koch reaction 

Ø the Reimer-Tiemann reaction 

53


Ø Kolbe reaction 

Ø Hoffmann-Maritus reaction and 

Ø Jacobsen reaction 

6.8. LESSON END ACTIVITIES 

1. The Gattermann Koch reaction for the formulation of an aromatic ring is regarded as 

aromatic electrophilic substitution reaction. Consider the following reaction sequence for 

the synthesis of benzaldehyde. 

C 6H 6 HCl C 6H 5CHO HCl 

CO 

If we use DCl in place of HCl, shall we get C6H5CHO or C6H5CDO, Give reason? 

2. Predict the product for the following reaction. 

(a) 

(b) 


ArH Zn(CN) 2 

CH 3 

HCl 

Hydrolysis 

CO 

HCl 

1. Briefly explain the mechanism and applications of Reimer-Tiemann reaction. 

2. Write notes on 

(a) Kolbe reaction 

(b) Hoffmann-Martius reaction 

(c) Jacobson’s reaction 





54


UNIT-III 

LESSON: 7 – ALIPHATIC NUCLEOPHILIC SUBSTITUTION 

CONTENTS 



7.2. SN1 MECHANISM 

7.2.1. STEREOCHEMISTRY OF SN1 REACTION 



7.4. SN i MECHANISM 

7.5. FACTORS AFFECTING NUCLEOPHILIC SUBSTITUTION 

7.5.1. SOLVENT 

7.5.2. NUCLEOPHILE 

7.5.3. LEAVING GROUP 

7.5.4. SUBSTRATE 

7.6. NEIGHBORING GROUP PARTICIPATION 

7.7. AMBIDENT NUCLEOPHILE 

7.8. AMBIDENT SUBSTRATES 







by which the aliphatic nucleophilic substitution reactions may proceed. 


* learnt possible reaction pathways in aliphatic nucleophilic substitution reactions. 

55



Nucleophilic substitution reaction involves the displacement of a nucleophile by another. 

These reactions have great synthetic importance. A classic example is the hydrolysis of alkyl 

halides. 

HO: + R : X HO:R + :X 

The nucleophile furnishes an electron pair to the carbon from which the leaving group 

departs with the bonding pair of electrons. Investigations by Ingold and co-workers indicate that 

nucleophilic substitution reaction can proceed by two different paths which have been designated 

by Ingold’s as SN1 and SN2 depending on the nature of the substrate, the nucleophile, the leaving 

group and the solvent. 


Kinetic studies of the hydrolysis of t-Butyl bromide indicate that the rate of the reaction is 

proportional to the concentration of the alkyl halide. (i.e.) rate µ [R3CX]. 

Since the rate of the reaction is dependent on one of the reactants, the reaction is a first order 

reaction. Nucleophilic substitution reaction which follows first order kinetics is designated SN1 

(substitution nucleophilic unimolecular). 

As the rate of the reaction is independent of [OH], it is interpreted that the halide 

undergoes slow ionization in the first step producing carbocation intermediate. In the second step 

a rapid attack of OH on the carbocation completes the hydrolysis. 

Me 

Me 

C 

Me 

Me 

Br 

Slow 

Me 

Me C + Br 

(i) 

Me 

Fast 

Me C + OH 

Me C 

Me 

The energy required for the ionization of the halide is supplied by the energy of salvation 

of the ions. Since a carbocation is formed in the slowest step, the alkyl halide which can most 

easily form a stable carbocation will favor hydrolysis by SN1 path. Hence, the order of hydrolysis 

of alkyl halides by SN1 path is: 

Allyl, Benzyl > 3 0 > 2 0 > 1 0 > CH3X 

Me 

Me 

OH 

(ii) 

56



Since a carbocation is flat (SP 2 , trigonal planar) with the vacant 2P orbital vertical to the 

plane bearing the three groups, the attack o the reagent can occur from either side of the plane 

with equal probability, i.e. a racemic product should result if the alkyl halide is chiral. 

HO 

C 

(+) 

R' 

R 

R'' 

Invertion of configuration 

R' 

R'' 

R 

C 

R' R 

C 

R'' 

OH 

-X 

X 

R' 

R 

R'' 

C 

(-) 

OH 

Retention of configuration 

Pure racemisation (50/50 mixture) is rarely observed. This is because the leaving group 

lies close to the carbocation shielding the side from the attack till it has sufficiently moved away. 

Thus, more attack of the reagent occurs from the opposite side to the leaving group. This causes 

more inversion than retention of configuration. Stable carbocations have longer life to permit 

salvation from either side of the plane of the carbocation resulting in greater proportion of 

racemisation. Greater proportion of inversion is observed with more nucleophilic solvent due to 

faster attack from the opposite side to the leaving group. 


Nucleophilic substitution reactions which follow second-order kinetics are called SN2 

(substitution nucleophilic reactions which follow second-order kinetics depending upon the 

concentrations of both the reactants. Thus, the rate of hydrolysis of methyl bromide with NaOH 

has been found to be of second order, i.e., 

the rate µ [CH3Br] [OH - ] 

Since the rate determining step involves both CH3Br and OH - , a collision between the two 

reactants resulting in the direct displacement of Br - by OH - occurs in such a way that while a new 

C-OH bond is being formed, the C-Br bond starts breaking, i.e. the bond formation and the bond 

breaking are simultaneous. Hence, the reaction is a concerted one step reaction without any 

intermediate. 

During the collision an energetic hydroxide ion approaches the methyl bromide molecule 

from the side opposite to bromine to avoid repulsion, i.e. at 180° to the leaving group- a backside 

attack. When the OH - is sufficiently near the electron-deficient carbon of the substrate, it 

57


begins to form a bond with it and the C-Br bond starts stretching. At one stage of the reaction, a 

state is reached when the OH and Br are partially bonded to the central carbon and the nonparticipating 

groups lying in a plane perpendicular to the line HO….C….Br. This state is called 

the transition state. In the transition state partial negative charge of the hydroxide ion is 

transferred to bromine via the carbon atom. With further approach of hydroxide, a complete 

C-OH bond is formed and bromine departs with the bonding pair of electrons. 

H H 

H H 

H 

H 

OH C Br 

d 

HO C 

d 

Br 

HO C + :Br 

H 

H 


In the transition state five groups or atoms are bonded to the a-carbon. As we go along 

the series from methyl bromide to t-butyl bromide, the increasing crowding of the carbon bearing 

the bromine atom progressively decreases the nucleophilic attack. Also, the increasing +1 effect 

along the series makes the carbon bearing the bromine progressively less positively polarized and 

consequently less readily attacked by the nucleophile. The steric factor is, however, more 

important than the electronic factor. Hence, the Eact for the formation of the transition state will 

be highest for 3° halides and least for methyl halides. Therefore, the rate of hydrolysis of alkyl 

halides by SN2 path is CH3X >1° > 2° > 3°, reverse of SN1 path. 


From the course of the direct displacement reaction as shown above, it is seen that the 

molecule is turned inside out. A Walden inversion is therefore expected to take place. An 

optically active halide on hydrolysis by SN2 path, therefore, should give an alcohol with 

inversion of configuration. The change of configuration can be established by observing the 

directions of optical rotation. In this case, however the substrate (bromide) and the product 

(alcohol) are two different compounds. The directions of rotation and the configurations of two 

different compounds are not usually related. Hence, the configurations of the substrate and the 

product should be related to arrive at the conclusion. 

An elegant method has been suggested (Huges and Ingold) to establish the inversion of 

configuration in SN2 reaction. The method involves the conversion of (+2) iodooctane with 

potassium radioiodide (K 128 I) in acetone to (-) 2-iodooctane. The reaction was found to be 

bimolecular (SN2), i.e. rate µ [C6H13CHICH3] [I*].The exchange of ordinary iodide with the 

radioactive iodide was accompanied by the loss of optical activity. This indicates the formation 

of (-) isomer from the (+) isomer to result in racemisation. 

H 

58


* I 

+ 

C 6H 13 

C 

Me 

H 

(+) 

I 

C 6H 13 

* d 

d 

I C I 

Me 

H 

* 

I 

C 6H 13 

Me 

The rate of loss of optical activity (i.e. racemisation) was found to be twice the rate of 

iodine exchange (i.e. inversion) - one (+) molecule is inverted and another (+) molecule pairs 

with it to form a (±) modification. The above formulated mechanism of SN2 reaction is therefore 

established. Inversion of configuration is always indicative of SN2 reaction. 

7.4. SN i MECHANISM 

It means Substitution Nucleophilic Internal mechanism. This follows second-order 

kinetics and yet with no change in the configuration of the product is identified as SNi. Thus, the 

esterification of chiral alcohols with thionyl chloride results in the retention of configuration of 

the product. 

Ph 

Me 

H 

C 

OH 

SOCl 2 

Me 

H 

Ph 

C 

Cl 

C 

H 

(-) 

+ SO2 + HCl 

The rate of the reaction is found to be dependent on both the reactants, i.e., 

rate µ [PhCH(Me)OH] [SOCl2]. Thionyl chloride reacts with alcohol to furnish alkyl 

chlorosulphite (1) which has the same configuration as the alcohol. There is evidence to show 

that the transformation of (1) to product involves an ion pair (2). The chloride ion is then 

supplied by the chlorosulphite anion for attack. The attack occurs from the front side since the 

chlorosulphite anion is held from the front side. Hence, no inversion of configuration is observed. 

+ 

59 

I


Ph 

Me 

H 

SO 2 

C 

+ 

OH 

Ph 

Me 

H 

+ 

C 

SOCl 2 

Cl 

HCl 

Ph 

Me 

H 

Ph 

Me 

The overall reaction may be considered as an internal attack. 

Ph 

Me 

H 

C 

O 

Cl 

S 

H 

Ph 

Me 

O C 

Hence the reaction is designated SNi as to distinguish it from SN2. 

When the reaction is carried out in the presence of pyridine, the pyridine hydroxide 

formed in the reaction supplies the effective nucleophile, Cl - , for a back-side attack as in normal 

SN2 reaction with inversion of configuration. 

Ph 

Ph 

O 

Me 

Cl + C O S Cl 

Cl C 

H 

C 5H 5N 

H 

C 

O 

Cl 

(1) 

C 

Cl 

O S 

7.5. FACTORS AFFECTING NUCLEOPHILIC SUBSTITUTION 

7.5.1. SOLVENT 

Me 

H 

O 

O 

Cl 

(2) 

+ 

Cl 

S 

S 

O 

SO 2 

O 

+ HCl C 5H 5NHCl 

SO 2 

+ + 

Polar solvents help in the separation and stabilization of unlike charges, i.e. aid 

ionization. In SN1 reaction ionization occurs in the rate determining step. Hence, polar solvents 

promote SN1 reaction. In SN2 reaction, the charge brought in by the nucleophile is spread over a 

60 

Cl


large part in the transition state. Hence polar solvents have little effect on the transition state. 

However, highly polar solvents form strong solvent layer around the nucleophile. Therefore, 

extra energy is required to break the solvent layer for the attack. Hence strongly polar solvents 

slightly slow down the SN2 reaction. 

7.5.2. NUCLEOPHILE 

In SN1 reaction a carbocation is attacked by the nucleophile. Hence, a low concentration 

of weak nucleophiles is sufficient for SN1 reaction. A high concentration of strong nucleophile 

may act as a base by accepting proton from suitable carbocation resulting in the formation of 

alkenes. In, SN2 reaction a high-energy transition state has to be formed. Therefore, a high 

concentration of strong nucleophile is required for SN2 reaction. 

7.5.3. LEAVING GROUP 

Less basic groups are better leaving groups because a strong base has a greater tendency 

for a backward direction in the reversible reaction 

HA H + + A - 

Strong bases such as OH , OR , R 2N , etc., are not good leaving groups. Thus alcohols are 

resistant to substitution in non – acidic medium. In acidic medium, however, the hydroxyl group 

leaves as H2O which is a weak base. 

R-OH 

H 

R-OH 2 

Br 

R-Br + H 2O 

Increase in the ionic size of the elements of the same group in the periodic table causes 

decrease in the basicity as the charge to size ratio decreases. The basicity order of the halogens is 

I RBr > RCl by 

either SN2 path. 

7.5.4. SUBSTRATE 

(a) For SN2 reactions 

The rate of direct displacement i.e., an SN2 reaction is very sensitive to the steric bulk of 

the substituents present on the carbon undergoing such as reaction. Thus is expected since the 

degree of coordination increases at the reacting carbon atom. Thus from the steric point of view, 

the optimum substrate would be CH3-X. Each replacement of hydrogen by a more bulky alkyl 

group should decrease the rate of reaction. Consequently, the order of reactivity of alkyl groups 

is expected to be methyl > primary > secondary > tertiary and this is observed. Table 7.5.4.1 

gives the relative rates of typical SN2 reactions. Methyl halides react most rapidly and tertiary 

halides react so slowly as to be unreactive by the SN2 mechanism. 

It may be noted that in E2 reactions the order of reactivities (see Scheme 7.5.4.1.) is the 

opposite to this, therefore, the SN2 / E2 ratio is largest for a primary halide while it is least for a 

tertiary halide and this is seen during the reactions of alkyl bromides with ethoxide ion in ethanol 

61


at 55 0 C (Scheme 7.5.4.2.). Thus tertiary halides do not give any significant yield in the SN2 

reactions. One may fail to prepare e.g., t-butyl cyanide from t-butyl chloride and cyanide ion, the 

product being the one derived from elimination, (CH3)2C = CH2. 

Table 7.5.4.1: Relative rates of reactions of alkyl halides in SN2 reactions 

Substituent Compound Relative rate 

Methyl 

1° 

2° 

3° 

CH3-X 

CH3-CH2-X 

(CH3)2-CH-X 

(CH3)3-C-X 

30 

1 

0.02 

0 

(CH 

B: 

3) 3C-Br (CH3) 2C=CH2 (I) 

(CH 3) 2CH-Br 

(II) 

CH 3CH 2-Br 

(III) 

B: 

B: 

Scheme 7.5.4.1 

CH 3CH=CH 2 

CH 2=CH 2 

faster 

Neopentyl halides are primary halides and even then these are unreactive in SN2 

reactions. This situation shows that steric hindrance effects are operative even if the b-carbon is 

substituted by alkyl groups. A general statement is therefore, that SN2 type displacements are 

retarted by increased steric repulsions at the transition state. In substrates of the type R-CH2-X, 

where X is a leaving group, showed that steric effects of R are the dominant factor in determining 

rates. For the reaction with iodide ion in acetone the relative reactivities of alkyl bromides were 

as shown (Scheme 7.5.4.3., good yields of neopentyl iodide can be obtained via Grignard 

reagent, see Scheme 7.5.4.4.). The bulky substituents on or near the carbon atom undergoing SN2 

reaction hinder the approach of the nucleophile to a distance within bonding range. 

H 3C 

H 3C 

H 3C 

CH 

H 2 

C Br H 3C 

Br 

(CH 3) 2CH OEt 

H 2 

C OEt + H 2C CH 2 

90% 10% 

+ H3C C 

H 

21% 79% 

CH 2 

62


CH 3 

H3C C Br 

(H3C) 2C CH2 CH 3 


100% 

In an extreme case within the series i.e., in neopentyl system (compared to methyl), the 

approach of the nucleophile along the line of the C-X bond is hindered by a methyl group, 

whatever geometry is attained by rotation about the single bonds (Scheme 7.5.4.3). 

backside 

attack Nu: C X 

relatively unhindered 

H 

Methyl halides 

H 3C 

Me 3C-CH 2Cl 

H 

H 2 

C Br H 3C 

H 

H 2 

C 

hindrance to the approaching 

nucleophile 

H3C Steric effects in the S N2 reaction 

H 2 

C 

Br 

(H 3C) 2HC 

Nu: 

H 2 

C Br 

H 3C 

CH 3 

C 

H 

H 

C X 

Neopentyl halides 

(H 3C) 3C 

1 0.8 4*10 -1 10 -5 

the relative rates 


XMg-R I-I R-I + MgXI 

Mg 

Mg 3C-CH 2MgCl 

I 2 

63 

H 2 

C Br 

Me 3C-CH 2I 

neopentyl chloride neopentyl iodide 


The halocycloalkanes display significant rate differences during SN2 reactions depending 

on the size of the ring. Halocyclohexanes although seemingly more capable of attaining sp 2 

hybridization at the reacting carbon are somewhat slower in SN2 reaction (see Table 7.5.4.2). 

When a nucleophile approaches an equatorial halide, it faces an inhibiting effect i.e., steric


hindrance by the two axial hydrogens at C-3 and C-5 carbons (Scheme 7.5.4.5). In a 

conformation where the leaving group is axial, then its exit its encounters steric hindrance. 

Table 7.5.4.2: Relative rates of reaction of alkyl bromides with lithium iodide in acetone 

H H 

I 

Alkyl group Relative rate 

Isopropyl 

Cyclopropyl 

Cyclobutyl 

Cyclopentyl 

Cyclohexyl 

Cycloheptyl 

Cyclooctyl 

H 

I 

1.0 


only tertiary halides react by SN1 mechanism. A tertiary carbocation being stabilized by three 

electron releasing groups (see, Scheme 7.5.4.7). Allylic and benzylic halides can also react by an 

SN1 mechanism since these substrates can form relatively stable carbocations (see e.g., Scheme 

7.5.4.8). 

CH 3 

CH 3 

C 

CH 3 

> CH3 CH CH3 > 

Stability of carbocations 3 ° > 2 ° > 1 ° > CH3 CH 2 

Electron release: Disperses charge, stabilizes ion 


CH 3 

CH 2 CH 2 CH 2 CH 2 

benzylic cation 

greater stability 

positive carbon is in conjugation with a double bond positive charge is spead over due to 

resonance 

H H 

C 

OCH 3 

CH 3 

H H 

C 

OCH 3 

CH 3 


H H 

C 

N 

O O 

CH 3 

H H 

C 

N 

O O 

65 

CH 3


Methyl chloromethyl ether, with ether group of +M type is hydrolyzed fast in water. The 

intermediate formed after heterolytic dissociation being the delocalized carbocation (oxonium 

ion, Scheme 7.5.4.9). 

CH 3O 

CH 2 

+ M type group 

OH 3C 

H 2O + 

-H + 

CH 2 

Cl 

-H + 

-Cl - 

OH 3C 

HO 

CH 3O 

CH 2 

CH2=O + CH3OH a hemiacetal 

+ 

CH 2 

H + 


H 

+ 

OH3C CH 3O + 

B strain and I strain effects are observed in many substrates and these effect the rate of 

SN1 reactions. When e.g., in a tertiary alkyl halide (R3Cl), one or more R groups are highly 

branched like e.g., t-butyl, the ionization is facilitated by relief of steric crowding in going from 

the tetrahedral ground state to the transition state for ionization and finally to the carbocation. 

This strain which may be present in a suitable substrate is called B strain. 

O 

H 

CH 2 

Similarly I strain effects SN1 solvolysis rates in some cyclic compounds. 

Nucleophilic SN1 substitutions at bridgeheads are impossible or very slow, since a rigid 

bridged system prevents rehybridization to a planar sp 2 carbon. However, when such a structure 

is flexible the SN1 reactions can take place, since now the bridgehead carbocation can be 

generated. (see, Scheme 7.5.4.10). 

Cl 

bridgehead 

(II) 

Br 

bridgehead 

CH 2 

(III) 

H 2O 

66 

+


+ 

the 1-trishomobarrelyl cation 

(IV) 

Scheme 7.5.4.10 

7.6. NEIGHBORING GROUP PARTICIPATION 

One has seen that nucleophilic substitutions take place with recemization or with 

inversion of configuration. However, in several cases such reactions occur with overall retention 

of configuration. One factor which leads to retention of configuration during a nucleophilic 

substitution is neighboring group participation. The neighboring group is an electron rich 

(Z:, Scheme 7.6.1) substituent present in the proper position for backside attack i.e.. anti attack to 

the leaving group (X). The process infact is a two step process. In the first step (Scheme 7.6.1) 

the neighboring group (acting as an internal nucleophile) attacks carbon at the reaction center 

(SN2 attack) and the leaving group is lost to give a bridged intermediate. This is then attacked in 

the second step by an external nucleophile (Y:, another SN2 attack) and the internal nucleophile 

goes back to where it came from, the net result is two consecutive SN2 reactions leading to 

retention of configuration at the reacting carbon. 

Z R 

R C C 

R 

X 

neighboring group 

R 

the leaving group 

Z 

R C C R 

R 

R 

the external nucleophile 

Y 

Z 

R C C R 

R 

R 

Z R 

R C C 

R 

Y 

R 

X 

step 1 

the neighboring group mechanism 

two S N2 substitutions, each causing an inversion 

the configuration at a chiral carbon is retained 

and not inverted or racemized 

step 2 

67


Scheme 7.6.1 

A graphic example of neighboring group participation is found in the conversion of 

2-bromopropanoic acid into lactic acid (Scheme 7.6.2). In the presence of concentrated sodium 

hydroxide, (S)-2-bromopropanoic acid (shown as its ion, Scheme 7.6.2) undergoes a bimolecular 

displacement with inversion of configuration as expected from the normal SN2 reaction. The 

same reaction when carried out in the presence of Ag2O and a low concentration of hydroxide 

ion, however, occurs with retention of configuration (Scheme 7.6.3). 

The reaction now involves two steps, in the first step the carboxylate group acts as a 

neighboring group to displace bromide ion via backside attack on the chiral center. The silver 

ion here acts as an electrophilic catalyst and aids the removal of bromine. In the second step, the 

a-lactone is attacked by a water molecule. Both the steps involve an inversion of configuration 

on the attacked carbon. Thus, the net result of two inversions in two steps is an overall retention 

of configuration. 

OH 

O2C H 

C 

H3C CH 3CHCO 2H 

Br 

2-bromopropanoic acid 

Br 

CO 2 

d d 

HO C Br 

H 

CH 3 

CH 3CHCO 2H 

OH 

Lactic acid 

CO 2 

C 

CH 3 

(S)-2-Bromopropanoate ion (R)-Lactate ion 

the normal stereochemical result for an S N2 reaction 

Scheme 7.6.2 

HO 

inversion of configuration 

H 

68 

Br


O O 

C 

C 

H 

H3C O 

C 

C 

CH 3 

Br 

O 

H 

Ag 

d 

O 

C 

O 

C 

d 

Br 

H CH3 Ag 

step 1 configuration of the stereocenter inverts 

d 

H2O C d 

H 

OH2 CH3 O 

C 

step 2 configuration of the stereocenter inverts 

O 

Scheme 7.6.3 

O 

C 

C 

CH 3 

O 

H 

an a - lactone 

O O 

C 

C 

H 

H3C OH 

69 

AgBr 

When the neighboring group participation operates during the rate determinating step of a 

reaction, the reaction rate is usually markedly increased. This effect is then termed anchimeric 

assistance. Sulfur atoms act as powerful nucleophiles and the participation of sulfur as a 

neighboring group is common. On reaction with water both hexyl chloride (I,Scheme 7.6.4) 

and 2-chloroethyl-ethylsulfide (II) give their corresponding alcohols. 

Relative 

rate 

1 

-700 

S 

(I) 

(II) 

Cl 

H2O Cl OH 

H 2O 

Scheme 7.6.4 

However the rate of reaction of sulfur containing compound (II) is much greater than that of the 

alkyl chloride. The reaction in the case of (I) is a simple SN2 displacement of chloride with 

water, while in the case of sulfide, it is the sulfur atom, which displaces the leaving group and 

acts as a neighboring group. The intramolecular reaction (as expected) is much faster than the 

intermolecular reaction. The initial product from (II) is an episulfonium ion which is then opened 

by second SN2 displacement (now intermolecular) to give the product (Scheme 7.6.5). 

S 

OH 

H


S 

(I) 

(II) 

H 2O 

the operation of a 

neighboring group effect 

Cl 

S N2 

Cl S 

Cl 

H H Cl 

O 

H 2O 

Scheme 7.6.5 

Episulfonium ion 

In a 1,2-disubstituted cyclohexane derivative, for the neighboring group participation to 

be operative the groups have to be anti to each other i.e., diaxial as in (I, Scheme 7.6.6). A ring 

flip may be necessary to bring about such an arrangement of the groups. Consider the acetolysis 

of cis and trans isomers of 2-acetoxycyclohexyl tosylate (Scheme 7.6.7) which give the same 

product I. 

Z 

(I) 

X 

H 

H 

Scheme 7.6.6 

H 

S 

X 

(II) 

H 

S 

Z 

OH 

OH 

H 

O 

HCl 

70 

H 

Cl 

HCl


OTs 

OAc 

AcO 

trans-2-acetoxycyclohexyl tosylate 

H 

cis-isomer 

OTs 

H 

OAc 

participation of the acetoxy 

carbonyl group 

OTs 

direct S N2 reaction 

O 

C 

O CH 3 

H 

H 

Scheme 7.6.7 

OAc 

OAc 

O 

OAc 

O 

(II) 

acetoxonium ion 

OAc 

H H 

OAc 

71 

CH CH 3 

The cis isomer reacts via a direct SN2 mechanism and the trans isomer reacts (about 700 

times faster) via neighboring group participation by involving an acetoxonium ion (II, Scheme 

7.6.7).The acetoxonium ion (the resonance hybrid structure) from the trans isomer is, 

symmetrical achiral (Scheme 7.6.8) and can be attacked by the acetate ion at either of the two 

equivalent carbons shown by arrows. Thus, if one starts with an optically active trans isomer, the 

net result is the formation of a racemic mixture of diacetates. 

O 

OTs 

CH 

O 

O 

O 

C CH 3 

Scheme 7.6.8 

H 

O 

O 

C CH 3 

Among the norbornyl derivatives (on acetolysis) the anti tosylate (III,Scheme 7.6.9) 

reacts 10 11 times faster than (I) while (II) has 10 4 times reactivity compared to (I). 

OTs TsO OTs 

(I) (II) (III) 

Scheme 7.6.9


The fastest rate of acetolysis of anti-tosylate (III) compared to (I, Scheme 7.6.9) proves 

the removal of the tosyl group (the rate determining step) with strong anchimeric assistance by 

the double bond. The resulting non-classical carbocation i.e., bridged ion can only react with 

acetate ion from the side opposite to the neighboring group, with retention of configuration 

(Scheme 7.6.10). In the syn-isomer (II, Scheme 7.6.9) the rate is slower because the double bond 

is not properly situated for participation. Thus this isomer dissociates without anchimeric 

assistance to give a homoallylic carbocation which rearranges to allylic carbocation (V, Scheme 

7.6.11) and this reacts to give an acetate. The high reactivity of (II) than (I) may be because of 

participation of s electrons of two allylic 1, 6 and 4, 5 bonds. 

3 

7 

2 

OTs OAc 

AcO 

anti-7-Norbornenyl 

tosylate 

(III) 

TsO 

1 

4 5 

1 

4 5 

(IV) 

6 

- - OTs 

7.7. AMBIDENT NUCLEOPHILE 

6 

AcO 

Bridged cation anti-Acetate 

Scheme 7.6.10 

(V) 

i.e., 

Scheme 7.6.11 

COCH 3 

Some nucleophiles have a pair of electrons on each of two or more atoms, or canonical 

forms can be drawn in which two or more atoms bear an unshared pair. In these cases the 

nucleophile may attack in two or more ways to give different products. Such reagents are called 

ambident nucleophiles. 

Some important ambident nucleophiles are: 

1. Ions of the type -CO-CR-CO-. These ions, which are derived by removal of a proton 

from malonic esters, b-keto esters, b-diketones, etc., are resonance hybrids: 

O 

72


C 

O 

R 

C 

CH 3 C C R 

O 

C 

O 

C C R 

They can thus attack a saturated carbon with their carbon atoms (C-alkylation) or with 

their oxygen atoms (O-alkylation): 

C C R 

O 

C 

OR' 

R'X 

C 

O 

R 

C 

C 

O 

R'X 

O 

C C R 

With unsymmetrical ions, three products are possible, since either oxygen can attack. 

With a carbonyl substrate the ion can analogously undergo C-acylation or O-acylation. 

2. Compounds of the type CH3CO-CH2-CO- can give up two protons, if treated with two 

moles of a strong enough base, to give dicarbanions: 

H 3C CO 

H 2 

C CO 

2 moles 

of base 

H 2C CO 

O 

R' 

H 

C CO 

Such ions are ambident nucleophiles, since they have two possible attacking carbon 

atoms, aside from the possibility of attack by oxygen. In such cases, the attack is virtually always 

by the more basic carbon. Since the hydrogen of a carbon bonded to two carbonyl groups is more 

acidic than that of a carbon bonded to just one, the CH group of 1 is less basic than the CH2 

group, so the latter attacks the substrate. This gives rise to a useful general principle: whenever 

we desire to remove a proton at a given position for use as a nucleophile but there is a stronger 

acidic group in the molecule, it may be possible to take off both protons; if it is, then attack is 

always by the desired position since it is the ion of the weaker acid. On the other hand, if it is 

desired to attack with the more acidic position, all that is necessary is to remove just one proton. 

For example, ethyl acetoacetate can be alkylated at either the methyl or the methylene group. 

R 

H 3C C 

O 

H 2 

C COOEt 

H 3C C 

1 mole 

of base 

2 moles 

of base 

O 

H 

RX 

C COOEt H3C C 

H 2C C 

O 

H 

C COOEt 

1 

RX 

O 

C 

O 

C 

O 

73 

CH COOEt


H 2C C 

R 

O 

C COOEt 

H 

H 2C C 

R 

O 

74 

H 2 

C COOEt 

3. The CN - ion. This nucleophile can give nitrites RCN or isocyanides RN º C. 

4. The nitrite ion. This ion can give nitrite esters R-O-N=O or nitro compounds RNO2, 

which are not esters. 

5. Phenoxide ions (which are analogous to enolate ions) can undergo C-alkylation or Oalkylation: 

O 

R 

R'X 

OR' 

R 

6. Removal of a proton from an aliphatic nitro compound gives a carbanion R 2C NO 2 

that can be alkylated at oxygen or carbon. O-alkylation gives nitronic esters, which are generally 

unstable to heat but break down to give an oxime and an aldehyde or ketone. 

O 

R 2C N O 

H 

C R' 

R'' 

There are many other ambident nucleophiles. 

7.8. AMBIDENT SUBSTRATES 

O 

R 

R' 

O 

R' 

R2C NOH R' C R'' 

Some substrates (e.g., 1,3-dichlorobutane) can be attacked at two or more positions. We 

may call these ambident substrates. In the example given, there happen to be two leaving groups 

in the molecule, but there are two kinds of substrates that are inherently ambident (unless 

symmetrical). One of these, the allylic type, has already been discussed. The other is the epoxy 

(or the similar aziridine or episulfide) substrate. 

R 

H 

C CH2O Y 

Y 

R 

O 

Y 

O 

R 

H 

C CH2Y O 

R


Substitution of the free epoxide, which generally occurs under basic or neutral conditions, 

usually involves an SN2 mechanism. Since primary substrates undergo SN2 attack more readily 

than secondary, unsymmetrical epoxides are attacked in neutral or basic solution at the less 

highly substituted carbon, and stereospecifically, with inversion at that carbon. Under acidic 

conditions, it is the protonated epoxide that undergoes the reaction. Under these conditions the 

mechanism can be either SN1 or SN2. In SN1 mechanisms, which favor tertiary carbons, we 

might expect that attack would be at the more highly substituted carbon, and this is indeed the 

case. However, even when protonated epoxides react by the SN2 mechanism, attack is usually at 

the more highly substituted position. Thus, it is often possible to change the direction of ring 

opening by changing the conditions from basic to acidic or vice versa. In the ring opening of 2,3epoxy 

alcohols, the presence of Ti(O-i-Pr)4 increases both the rate and the regioselectivity, 

favoring attack at C-3 rather than C-2. When an epoxide ring is fused to a cyclohexane ring, SN2 

ring opening invariably gives diaxial rather than diequatorial ring opening. 

Cyclic sulfates (2), prepared from 1, 2-diols, react in the same manner as epoxides, but 

usually more rapidly: 

C 

OH 

C 

Y 

C 

OH 

OSO 3 

C 


SOCl 2 

CCl 4 

C 

O 

SO 


Pointed out 

Ø SN1 mechanism 

Ø Stereochemistry of SN1 reaction 

Ø SN2 mechanism 

Ø Stereochemistry of SN2 reaction 

Ø SN i mechanism 

Ø Factors affecting nucleophilic substitution 

Ø Neighboring group participation 

Ø Ambident nucleophile 

Ø Ambident substrates 

H 


C 

O 

NaIO 4 

RuCl 3 

1. What are the evidences for the intermediacy of carbonium ion in SN1 reactions? 

2. Why CH3OCH2Cl reacts with iodide ion in acetone several thousand times faster than 

CH3Cl? 

C 

H 

OH 

C 

C 

O 

SO 2 

C 

O 

(2) 

Y 

75


3. What is neighboring group participation? 

4. Why the reaction of a bromo propionate (optically active) in methyl alcohol gives a 

product with retention of configuration? 


1. Define SNi reaction. Discuss cyclic as well as ion pair mechanism for SNi reaction. How 

do both the mechanisms explain the observed results of these reactions including 

stereochemistry? 

2. Briefly explain the various factors affecting the Nucleophilic Substitution Reaction. 

3. Write notes on 

(a) Ambident nucleophile 

(b) Ambident substrate 





3. S.N. Sanyal, Reactions, rearrangements and reagents, Bharati Bhavan (P&D), Patna. 

76


LESSON: 8 – NUCLEOPHILIC SUBSTITUTION AT ALLYLIC AND 

VINYLIC CARBON 

CONTENTS 



8.2. ALLYLIC REARRANGEMENT (ALLYLIC SHIFT) 

8.3. SN2 REACTIONS WITH ALLYLIC AND VINYLIC SYSTEMS 

8.4. NUCLEOPHILIC SUBSTITUTION AT A BRIDGEHEAD CARBON 







by which the nucleophilic substitution reactions at allylic and vinylic carbon compounds may 

proceed. 


* learnt possible reaction pathways in nucleophilic substitution reactions at allylic and 

Vinylic carbon compounds. 


Allylic substrates e.g., allylic halides undergo nucleophilic substitution reactions 

especially rapidly and are usually accompanied by a rearrangement known as an allylic 

rearrangement (allylic shift). 

8.2. ALLYLIC REARRANGEMENT (ALLYLIC SHIFT) 

When allylic substrates are treated with nucleophiles under SN1 conditions two products 

are usually obtained, one is normal and the other is rearranged. This is seen in the case of either 

1-chloro-2-butene or 3-chloro-1-butene (Scheme 8.2.1). Two products are formed since the 

intermediate carbocation which is formed is a resonance hybrid, and consequently C1 and C3 

each carry a partial positive charge and both are attacked by the 

77


CH 3CH=CHCH 2Cl 

-Cl 

4 3 2 1 

CH3CH=CHCH 2 

CH3CHCH=CH 2 

4 3 2 1 

Allylic cation 

(resonance structures) 

OH 

H 2O 

CH 3CH=CHCH 2OH CH 3CHCH=CH 2 

2-Buten-1-ol 3-Buten-2-ol 

-Cl 

H 

Cl 

CH 3CHCH=CH 2 

3-chloro-1-butene 

Scheme 8.2.1 

nucleophile (OH - ). An allylic rearrangement cannot, however be detected in the case of 

symmetrical allylic cations. Moreover, different allylic halides may give identical products upon 

solvolysis, if they, dissociate to the same allylic cation (Scheme 8.2.1). This mechanism has been 

called SN1’ mechanism (i.e., substitution unimolecular with rearrangement). 

8.3. SN2 REACTIONS WITH ALLYLIC AND VINYLIC SYSTEMS 

The allylic systems are prone to react by SN1 mechanism since these form 

delocalized allylic carbocations easily. However, the synthetic utility of these reactions is limited 

due to the allylic shift of the double bond. It is possible to have suitable reaction conditions 

under which allylic bromides react cleanly (without rearrangement) by way of the SN2 

mechanism. Thus allyl bromide undergoes bimolecular substitution about 40 times faster than npropyl 

bromide. In the case of allylic system, the transition state receives resonance stabilization 

through conjugation with the p orbitals of the pi bond, (Scheme 8.3.1). The electronic structure 

of this transition state resembles the structure of the allyl anion. The stabilization of the 

transition state via the conjugation with the p orbital which is momentarily generated on the 

reacting carbon atom lowers the activation energy of the system, increasing the reaction rate. 

H 

H 

C 

C C 

Br 

Nu: 

H 

H 

H 

H 

C 

Nu 

C C 

Br 

H 

H 

transition state 

S N2 reaction on allyl bromide 

H 

H 

C 

H 

C C 

Br 

Nu 

78 

H 

H


H 3CH 2C 

C 

Br 

Nu: 

H 

H 

Nu 

H 

H3CH2C C 

H 

H3CH2C C 

Br 


S N2 reaction on propyl bromide 

(Scheme 8.3.1) 

Haloalkenes, in which the halogen is directly attached to the unsaturated carbon and 

phenyl halides, display exceptionally low reactivity either by SN1 or SN2 mechanism. Thus while 

n-propyl chloride (CH3CH2CH2Cl) undergoes rapid substitution with potassium iodide in acetone 

1-chloropropene (CH3CH=CHCl) is inert. Simple alkenyl halides e.g., vinyl chloride 

(CH2=CHCl) also do not form carbocations readily. This is due to increased strength of the vinyl 

halogen bond (see, Scheme 8.3.2) in Vinylic and phenyl halides. Moreover, the electrons of the 

double bond of benzene ring repel the approach of the nucleophile from the backside to be 

unreactive by SN2 mechanism, SN1 reaction is also retarded due to the instability of phenyl 

cation. 

H 

H 

C 

C 

H 

Cl 

CH 2=CH-X CH 2-CH=X 

Vinyl chloride 


a +M effect 

SN1 type of solvolysis leading to Vinylic cations can however, be carried out on suitable 

substrates provided one has an efficient leaving group) and the Vinylic group contains electron 

releasing groups (Scheme 8.3.3, see also Scheme 8.3.2). 

C C 

OTf 

A vinylic triflate 

(a "super" leaving group) 

C C 


A vinylic cation 

OTf 

CF 3SO 3 

Triflate ion 

Nu 

Br 

79 

H 

H


8.4. NUCLEOPHILIC SUBSTITUTION AT A BRIDGEHEAD CARBON 

When the leaving group e.g., at [2.2.1] bridgehead is such that it cannot function as a 

nucleophile i.e., to come back once it has gone, then a nucleophilic substitution can occur. Thus 

(I) undergoes substitution with chlorobenzene as the nucleophile to give (II). 

O 

C 

Cl 

O 

PhCl 

AgBF 4 

(I) (II) 



Pointed out 

Ø SN1 reactions with allylic and vinylic systems 

Ø SN2 reactions with allylic and vinylic systems 

Ø Nucleophilic substitution at a bridgehead carbon 


1. Why the allylic systems are prone to react with SN1 mechanism? 

2. Write short notes on nucleophilic substitution at a bridgehead carbon. 


Cl 

80 

CO 2 BF 3 AgCl HF 

1. Comment upon the nucleophilic substitution reactions of allylic and Vinylic carbon 

compounds. 



international publishers.


LESSON: 9 – TYPICAL ALIPHATIC NUCLEOPHILIC SUBSTITUTION 

REACTIONS 

CONTENTS 


9.1. VON BRAUN REACTION 

9.2. THE CLAISEN CONDENSATION 

9.3. HYDROLYSIS OF ESTERS 

9.3.1. BASIC HYDROLYSIS (the BAC2 Mechanism) 

9.3.2. ACIDIC HYDROLYSIS (The AAC2 Mechanism) 

9.3.3. THE ACYLIUM ION MECHANISM (The AAC1 Mechanism) 

9.3.4. THE CARBONIUM ION MECHANISM (The AAL1 Mechanism) 




9.7 REFERENCES 



by which the aliphatic nucleophilic substitution reactions may proceed. 

On successful completion of this lesson the student should have learnt possible reaction 

pathways in typical aliphatic nucleophilic substitution reactions. 

9.1. VON BRAUN REACTION 

The von Braun reaction involves the cleavage of tertiary amines by cyanogen bromide to 

afford an alkyl bromide and a disubstituted cyanamide. Cyanogen bromide reacts with tertiary 

nitrogen compounds to break one carbon to nitrogen linkage. 

N 

R 

R3N + BrCN ® R2N-CN + R-Br 

BrCN 

CH2Br N-CN 

Usually, the smallest alkyl group or that would furnish the most reactive halide (e.g. 

benzyl or allyl) is cleaved. The reaction can also be run on secondary amines, but the yields have 

been found to be poor. 

R 

81


Mechanism 

R 

R 

N 

R 

CH 3 

NC Br 

N 

S N2 

- Br 

BrCN 

Br 

9.2. THE CLAISEN CONDENSATION 

R 

R N CN 

R 

(N-cyanoammonium 

bromide intermediate) 

CH 3 

N 

CN 

S N2 

Ethyl acetate can be converted to ethyl acetoacetate. 

2 CH 3COOC 2H 5 

Br 

R 2N-CNH R-Br 

In this reaction cyanogen bromide, a 

single reagent is resp onsible for tw o 

transformations in one reaction v essel; 

hence NC-Br is called a counterattack 

reagent 

CH 3COCH 2COOC 2H 5 

The reaction is known as Claisen condensation and it covers various condensations 

between a carboxylic ester and an a-hydrogen containing ester, ketone or nitrile, yielding a 

b-ketoester, ketone or nitrile, respectively. These reactions are usually carried out by means of 

sodium ethoxide in ethanol solution. Claisen condensation resembles aldol condensation in the 

sense that it involves the attack of a carbanion, generated by the removal of acidic hydrogen, on 

the carbonyl carbon of the ester. Expulsion of the ethoxide ion then yields the product. 

O 

H 3C C 

O 

H 3C C 

O 

H 3C C 

O C 2H 5 + C 2H 5O C 2H 5OH + 

OC 2H 5 

OC 2H 5 

O 

O 

H 2C C 

O 

O C 2H 5 H 2C C 

+ H2C C O C2H5 H3C C 

O 

H2 C C 

OC 2H 5 H 3C C 

O 

O 

OC 2H 5 

O 

H2 C C 

O C 2H 5 

OC 2H 5 

CH 2COOC 2H 5 + OC 2H 5 

82


The reversible formation of carbanions in the above sequence has been demonstrated by 

treating ester with C2H5OD containing sodium ethoxide whereby these esters underwent 

hydrogen exchange at the a-position. 

O 

C C 

H 

O 

O C 2H 5 

+ C 2H 5O C C 

C C O C 2H 5 C 2H 5OD 

+ C C 

D 

O 

O 

O C2H5 + C2H5OH O C 2H 5 

+ 

C 2H 5O 

It was also observed that the rates of exchange of these hydrogens parallel the reactivity 

of these esters in Claisen condensation. The same conclusion was reached by the observation 

that optically active esters containing an a-hydrogen racemize in the presence of sodium 

ethoxide. 

Since these steps are reversible, the success of Claisen condensation depends upon the 

removal of the final product from the reaction site and thus forcing the equilibrium to the right. 

Usually this is done by converting the product ester into an enolate anion which is stabilized by 

resonance. 

O O 

H2 

H3C C C C OC2H5 + C2H5O C2H5OH + 

O 

H 3C C 

O 

H 

C C 

O 

OC 2H 5 H 3C C 

O 

H 3C C 

O 

CHC 

O 

H 

C C 

OC 2H 5 

OC 2H 5 

It follows that when the product b-ketoester does not have an a-hydrogen, the 

equilibrium of the condensation cannot be shifted to the right and hence esters without two a ahydrogens 

do not undergo Claisen condensation in the presence of sodium ethoxide. The 

equilibrium in such reactions, however, may be forced to the right by the use of more strongly 

83


basic catalysts, such as sodium triphenylmethide and sodium amide which are capable of 

bringing about the formation of b-ketoesters that contain no a-hydrogen atoms. 

O 

HC(H 3C) 22 C 

HC(CH 3) 2 

O 

C 

CH 3 

O 

OC2H5 Ph3C HC(CH3) 2 C 

C COOC 2H 5 

CH 3 

9.3. HYDROLYSIS OF ESTERS 

Ph 3C 

HC(CH 3) 2 

O 

C 

CH 3 

C COOC 2H 5 

CH 3 

CH 3 

+ 

C COOC2H5 + 

CH 3 

84 

C 2H 5OH 

C 2H 5OH 

There are a number of distinct mechanisms by which esterification of an acid and the 

hydrolysis of an ester may proceed. This plurality of mechanisms is due to the following three 

reasons: 

(i) Esterification and hydrolysis may proceed either through an acyl-oxygen bond 

cleavage (A) or an alkyl-oxygen bond cleavage (B). 

O 

R C 

O 

R C 

O 

O R' + H2O hydrolysis 

esterification 

R C 

O 

O R' + H2O hydrolysis 

esterification 

R C 

O H + R'OH A 

O H + R'OH B 

(ii) Hydrolysis of an ester may be accomplished either by acids or alkalis and depending 

upon the reagent, the species undergoing hydrolysis may be a neutral ester molecule (R-COOR’) 

or an ionic conjugate acid (RCOOHR) + . 

(iii) The esterification and hydrolysis may proceed either by a unimolecular or a 

bimolecular mechanism. 

Since esterification in basic medium is not possible because of the conversion of 

carboxylic acid to a resonance-stabilized carboxylate anion, depending upon the above three 

factors, there are four possible mechanisms by which esterification may proceed. Similar 

considerations visualize eight mechanisms for ester hydrolysis. Ingold has suggested a shorthand 

notation to describe these bewildering number of mechanisms in which A or B refers to the 

acidic or basic (and neutral) medium; acyl-oxygen or alkyl-oxygen cleavage is symbolized by 

AC or AL, respectively and molecularity of the reaction is indicated by the usual numbers 1 or 2. 

Thus by a BAC2 hydrolysis we mean a bimolecular basic hydrolysis of an ester proceeding 

through the acyl-oxygen bond cleavage. In the following pages we shall exemplify a few of the 

relatively more common mechanisms.


9.3.1. BASIC HYDROLYSIS (the BAC2 Mechanism) 

The hydrolysis of esters by hydroxide ions in aqueous solution is kinetically a secondorder 

reaction, first order in ester and first order in hydroxide ion. It is, therefore, a bimolecular 

reaction. The evidence for the acyl-oxygen bond fission is provided by carrying out the 

hydrolysis of n-amyl acetate in water enriched in 18 O and then isolating n-amyl alcohol without 

18 O. 

O 

H 3C C 

O C 5H 11 + H 2O 18 

O 

H 3C C 

18 

O H + 

C 5H 11OH 

The hydrolysis can thus be depicted as involving a BAC2 reaction for which two 

mechanisms are consistent with the above data. 

(i) 

O 

OH + C 

R 

O 

(ii) OH + C 

OR' 

OR' 

R 

O 

HO C OR' HO C + OR' 

O 

R 

O 

R 

O 

85 

O C + R'OH 

HO C R HO C R + OR' 

OR' 

O 

O 

O 

C 

R 

R 

+ 

R'OH 

In the first of these two mechanisms there is a transition state (SN2 reaction) with an 

energy maximum in the reaction coordinate whereas the second mechanism postulates a true 

intermediate with energy minimum. Bender solved the problem of deciding between these two 

mechanisms by hydrolyzing esters (ethyl, isopropyl and t-butyl benzoates) labeled in the 

carbonyl group with 18 O in ordinary water containing hydroxide ions. When the hydrolysis was 

stopped before completion, unreacted esters were found to contain less 18 O content. This 

decrease in 18 O content of the ester cannot be explained by the first mechanism as it is a 

concerted process. But if we assume that the proposed tetrahedral intermediate (I) of the second 

mechanism lives long enough to survive a proton shift and establish an equilibrium with another 

intermediate (II) then the two oxygen atoms become equivalent. Since the basicities of alkoxide 

and hydroxide ions are comparable, the two intermediates may lose these ions at comparable


rates (paths a and b, respectively) and then it appears quite reasonable to expect unlabelled ester 

to be formed in the process. 

R 

18 

O 

C 

OR' 

+ 

HO 

O 

R C OH 

18O 

R'OH + R C 

R'O + 

18 

OR' 

OR' 

(I) (II) 

R 

OH 

C 

O 

18 

OH 

R C O 

O 

OR' 

Electron-withdrawing substituents in either the acyl or alkyl part of the ester facilitate 

attack by hydroxide ions. 

18 

a 

R 

b 

C O 

The effects of substituents on BAC2 hydrolysis of aromatic esters fall in line with the 

above conclusions. It was observed that the substituents Cl, Br and NO2 group accelerate the 

reaction while CH3, p-OCH3 and NH3 groups retard it. 

9.3.2. ACIDIC HYDROLYSIS (The AAC2 Mechanism) 

Acid-catalyzed hydrolysis of esters is a reversible reaction unlike base-catalyzed 

hydrolysis. The principle of microscopic reversibility tells us that the mechanism of the reverse 

reaction is known with as much certainty as is the mechanism of the forward reaction. This 

means that a study of the mechanism of acid-catalyzed hydrolysis will automatically establish the 

mechanism for acid-catalyzed esterification. 

The rate of acid-catalyzed hydrolysis of common esters is found to be proportional to 

both H + and the ester and when the hydrolysis is carried out in the presence of H2 18 O, the product 

alcohol has no 18 O content. Thus, it is an AAC2 reaction. 

O 

HOOCCH 2CH 2COC 2H 5 

+ 

18 H 

H2O O 

18 

HOOCCH 2CH 2COH 

+ 

+ 

18 

C 2H 5OH 

Again Bender observed the loss of 18 O content in the unreacted ethylbenzoate when the 

hydrolysis was stopped before completion. This loss can only be explained by assuming two 

intermediates III and IV whose life is long enough to permit proton exchange thus making the 

two oxygen atoms equivalent. 

R 

18 

O 

C 

OR' 

H 

-H 

R 

18 

OH 

C 

OR' 

H 2O 

-H 2O 

18 

OH 

R C OH2 OR' 

(III) 

86 

OH


R 

18 OH2 R C OH 

C O 

OR' 

OR' 

(IV) 

+ 

18 

H 2O + H 

OH 

(III) R C OH 

R 

18 

OH 

C 

18 

O 

OR'H 

+ R'OH 

In contrast to basic hydrolysis, acidic hydrolysis (and esterification) is rather insensitive 

to polar effects. This appears quite reasonable as the two parts of the process, protonation and 

subsequent nucleophilic attack by water, require two opposing electronic influences. Electrondonating 

groups accelerate protonation, but they inhibit the subsequent attack by a nucleophile. 

On the other hand, electron-withdrawing substituents repress protonation but they accelerate the 

nucleophilic attack. These reactions, however, are subject to steric effects; for instance, 

esterification of 2-methyl benzoic acid is retarded while that of 2, 6-dimethylbenzoic acid is 

completely prevented. 

9.3.3. THE ACYLIUM ION MECHANISM (The AAC1 Mechanism) 

Hydrolysis and esterification of sterically hindered compounds, such as derivatives of 

trialkylacetic acids and ortho disubstituted benzoic acids, are carried out by dissolving them in 

concentrated sulphuric acid and then pouring this solution into cold water (for hydrolysis) or into 

an alcohol (for esterification). Mesitoic acid (2,4,6-trimethylbenzoic acid; (V) provides a good 

example of this type whose solution in concentrated sulphuric acid indicates the presence of four 

particles. The available evidence indicates that like AAC2 mechanism, there is an initial 

formation of an oxonium ion by the addition of a proton to the substrate which then undergoes a 

rate-controlling heterolytic fission to yield an acylium ion (VI). 

R COOH + 2H2SO4 RCO + H3O + 2HSO4 V VI 

R = 

H 3C 

H 3C 

CH 3 

+ 

H 

87


The acylium ions are linear and their formation is favored primarily because of relief in 

the steric strains of the sterically hindered compounds. Another factor that favors their formation 

is the conjugation of the -C º O + group with the unsaturated system thus delocalizing the positive 

charge over the whole ion VI. A rapid attack by water or alcohol on this ion results in the 

formation of acid or ester, respectively. Thus esterification (or hydrolysis of methyl ester) of 

mesitoic acid proceeds as follows: 

H 3C 

H 3C 

H 3C 

OR 

CH 3 

CH 3 

CH 3 

CH 3 

CH 3 

CH 3 

COOH 

COOCH 3 

COOCH 3 

CH 3OH 

VI 

H 3C 

H 3C 

H 2O 

H 3C 

9.3.4. THE CARBONIUM ION MECHANISM (The AAL1 Mechanism) 

VI 

CH 3 

CH 3 

CH 3 

CH 3 

C 

C 

O 

O 

CH 3 

CH 3 

88 

COOH 

When groups such as tert-alkyl, benzyl, etc., capable of forming stable carbonium ions 

are the alkyl moiety in the substrate, hydrolysis and esterification may place by an alkyl-oxygen 

bond cleavage. A mechanism of this type occurs in the solvolysis of tert-butyl benzoate which 

on treatment with methanol and acid gives tert-butyl methyl ether and benzoic acid, rather than 

tert-butyl alcohol and methyl benzoate, the products of normal solvolysis. The following 

mechanism is consistent with the product analysis.


O 

C 

C(CH 3) 3 + H C 

OH 

OH 

C(CH 3) 3 + CH 3OH (CH 3) 3C OCH 3 + H 

C 

O C(CH 3) 3 

O 

+ 

C(CH 3) 3 

Conformation of this mechanism is provided by carrying out the hydrolysis in H2 18 O. 

O 

C 

O C(CH3) 3 + H2O 18 H 

O 

C 

89 

OH (CH3) 3C18 + 

OH 

This type of mechanism has been labeled as AAL1 mechanism. The intermediate has 

features so characteristic of a free carbonium ion, i.e., its recemization and rearrangement, if the 

structure permits. 



Pointed out 

Ø Vonbraun reaction 

Ø The Claisen condensation 

Ø Hydrolysis of esters 


1. Explain Vonbraun reaction with mechanism. 

2. Ethyl 2-methyl propionate (I) fails to undergo the Claisen reaction with sodium ethoxide 

in ethanol and the possible product (II) is not isolated. Explain.



OEt 

(I) (II) 

3. Discuss the mechanism of Claisen Condensation. How will you synthesize a b-ketoester 

without a-hydrogen atoms? 

4. Classify the various mechanisms by which esterification of an acid and the hydrolysis of 

an ester may proceed. Discuss their mechanism. 


1. Goutam Brahmachari, Organic name reactions, Narosa publishing house, New Delhi. 

OEt 

2. S.M. Mukherji and S.P. Singh, Reaction mechanism in Organic Chemistry. 

90


CONTENTS 

UNIT-IV 

LESSON: 10 – ELIMINATION REACTION 


10.2. E1 MECHANISM 

10.2.1. DEHYDROHALOGENATION OF ALKYL HALIDES 

10.2.2. EVIDENCE FOR E1 MECHANISM 


10.3.1. EVIDENCES FOR THE EXISTENCE OF E2 MECHANISM 

10.4. E1CB MECHANISM 

10.5. INTRAMOLECULAR ELIMINATION (Ei) 

10.5.1. EVIDENCE FOR THE EXISTENCE OF THE Ei MECHANISM 

10.5.2. HYDROACYLOXY ELIMINATION 

10.6. STEREOCHEMISTRY OF ELIMINATION REACTIONS 

10.7. ELIMINATION VS SUBSTITUTION 

10.7.1. STRUCTURE OF THE SUBSTRATE 

10.7.2. NATURE OF THE BASE 

10.7.3. NATURE OF SOLVENT 

10.7.4. EFFECT OF TEMPERATURE 







by which the elimination reactions may proceed. 


* learnt possible reaction pathways in elimination reactions. 


When two groups or atoms from adjacent carbons are eliminated with the formation of 

unsaturated compounds the reaction is called elimination reaction. Most commonly a nucleophile 

and a proton from the b-carbon are eliminated. Hence the reaction is known as 1,2- or a,belimination 

or b-elimination. 

91


(i) 

b 

C 

H 

X 

a 

C 

(ii) C C 

Some similar elimination reactions are 

X 

-HX 

-HX 

(1) Dehydrohalogenation of alkyl halide by base. 

RCH 2CH 2 X 

OH 

(2) Dehydration of alcohols by acids. 

RCH 2CH 2 OH 

(3) Hofmann’s degradation of quaternary bases by heat. 

RCH 2CH 2 NR 3OH 

H 

D 

C C 

C C 

RCH=CH 2 H 2O X 

RCH=CH 2 H 2O H 

RCH=CH 2 

The presence of at least one hydrogen atom on the b carbon is necessary for elimination. 

The driving forces for elimination are 

(a) Stability of the olefin formed 

(b) The relief from steric strain due to crowding in the substrate. 

Branching at the b carbon of the substrate produces substituted olefins stabilized by 

hyperconjugation and hence favors elimination. 

Strain in the substrate due to crowding by the substituents can be relieved on the 

formation of olefin since the bond angles increase from 109.5 0 in the substrate (sp 3 hybridized) to 

120 0 in the product (Sp 2 hybridized). Hence 3 0 halides favor elimination most and 1 0 halides the 

least. i.e., the order of the elimination in halide is 3 0 >2 0 >1 0 . 

R 3N 

H 2O 

The elimination reaction may proceed by either unimolecular or bimolecular mechanism. 

92



The E1 mechanism is a two step process in which the rate determining step is ionization 

of the substrate to give a carbocation that rapidly loses a b-proton to a base. 

Slow 

Step 1 C C X 

H C C X 

H 

Step 2 C 

H 

Solvent 

C C C 

E1 mechanism reaction the product should be completely nonstereospecific, since the 

carbocation is free to adopt its most stable conformation. 

10.2.1. DEHYDROHALOGENATION OF ALKYL HALIDES 

The rate of elimination of a halo acid from t-butyl bromide in basic medium is found to 

be proportional to [Me3CBr]. Therefore, the halide undergoes slow ionization in the first step. 

This is followed by a rapid extraction of a proton from the carbocation by the base or solvent in 

the second step. 

H 3C 

H 3C 

CH 3 

C 

CH 3 

C 

H 2C 

CH 3 

Br 

H 

slow 

H 

fast 

CH 3 

H3C C Br (i) 

CH 3 

CH 3 

H3C C H2O (ii) 

The carbocation is formed in the first step in E1 reaction. Hence the reagent can attack 

the carbon to give substitution product and also can accept a proton to give elimination product. 

In practice both alcohol and alkene are obtained on hydrolysis of Me3CBr. 

CH 2 

93


H 3C 

C 

CH 3 

CH 3 

OH 

(nucleophile 

substitution) 

OH 

(base 

elimination) 

H 3C 

H 3C 

H 3C 

CH 3 

C 

CH 3 

OH 

C CH 2 

When more than one alkene can be formed, the alkene will predominate which has large 

number of alkyl groups on the double-bonded carbons – this is Saytzev’s rule. This is 

understandable since the substituted alkyl groups will stabilize the alkene by hyperconjugation. 

CH 3 

H3C C C CH3 H 

Cl 

H 

-HCl 

CH 3 

10.2.2. EVIDENCE FOR E1 MECHANISM 

CH 3 

H3C C C 

H 

CH3 H3C C 

H 

C 

H 

CH2 Major Minor 

1. The reaction exhibits first order kinetics as expected. Solvent does not appear in the rate 

equation, even if it were involved in the rate determining step, but this point can be checked by 

adding a small amount of the conjugate base of the solvent. This addition does not increase the 

rate of the reaction. An example of an E1 mechanism with a rate determining second step has 

been reported. 

2. If the reaction is performed on two molecules that differ in the leaving group the rates should 

obviously be different. Since, they depend on the ionizing ability of the molecule. 

t BuCl 

36.3% 

63.7% 

H 3C 

C CH2 

CH 3 

t BuOH 

35.7% 

64.3% 

t BuSMe 2 

3. If carbocations are intermediates, we expect rearrangements with suitable substrates. These 

have often been found in elimination reaction performed under E conditions. 

E1 reactions can involve ion pair. This effect is naturally greatest for nondissociating solvents. 

E1 reaction is facilitated by: 

(i) Branching at the a and b carbons of the substrate – for the stability of the olefin. 

94


(ii) Strong polar solvent – to acid ionization. 

(iii) Low concentration of base–the greater stability of the alkene over the carbocation 

makes the extraction of proton easy. 


When the rate of elimination reaction is dependent on both the substrate and the reagent 

the reaction is kinetically second order or bimolecular. 

OH 

H 

C C 

X 

OH 

H 

C C 

X 


H 2O C C X 

The base abstracts a proton from the b-carbon; simultaneous departure of the nucleophile 

takes place from the a-carbon. In the transition state the b-C-H and a-C-X bonds are stretched 

on the attack of the reagent with incipient p-bond formation. 

The energy of the transition state will be least when two leaving groups, the a and b 

carbons and the attacking base are coplanar in the transition state. Also, the two leaving groups 

(H and X) should be trans to each other to effect p bond. 

The two leaving groups orient themselves in the trans position when a s bond exists 

between the a and b carbons. However, free rotation is not allowed as in the case of double 

bond, the elimination is difficult when two leaving groups are cis to each other. Thus, acetylene 

dicarboxylic acid is more easily formed from chlorofumaric acid (1) than from chloromaleic acid 

(2). 

HOOC 

Cl COOH 

C 

C 

H 

Leaving groups 

trans (1) 

-HCl 

fast 

COOH 

C 

C 

COOH 

-HCl 

10.3.1. EVIDENCES FOR THE EXISTENCE OF E2 MECHANISM 

Cl COOH 

C 

H 

C 

COOH 

Leaving groups 

cis (2) 

1. The reaction displays the proper second-order kinetics. 

2. When the leaving hydrogen is replaced by deuterium in second order elimination there is an 

isotope effect with breaking of cis bond in the rate determining step. This result proves that E2 

mechanism. E2 is stereospecific it is found from stereochemical studies. 

E2 reaction is facilitated by: 

95


1. branching at a and b carbons since more stable olefins is formed. 

2. Strong base of high concentration since a strong C-H bond has to break. 

3. Solvent of low polarity. 

10.4. E1CB MECHANISM 

The second-order elimination reaction may as well proceed in two steps as on E1 

reaction. The first step involved a fast and reversible removal of a proton from the b-carbon 

with the formation of a carbon ion which then loses the leaving grouping in the second slow rate 

determining step. 

H 

C 

C 

Br 

C C 

Br 

EtO 

Slow 

Fast 

C C 

Br 

C C Br 

EtOH 

The overall rate of this reaction is thus dependent on the concentration of the conjugate 

base of the substrate. Hence this designated as E1CB. 

To distinguish between E2 and E1CB mechanism, deuterium exchange experiment was 

performed. 

For this 2-phenyl ethyl bromide was treated with sodium ethoxide in EtOD. This 

substrate was selected because the Ph group is expected to increase the acidity of b- hydrogen 

and also to stabilize the carbanion to exist long enough for the incorporation of deuterium in the 

starting from the solvent EtOD. 

EtO 

H 

Ph C 

H 

H2 C Br 

EtO 

fast 

Ph 

H 

C CH 2Br 

EtOD 

D 

(1) 

Ph C 

H 

H2 C Br 

Ph 

D 

C CH2Br Ph C 

D 

CH2 Br 

The reaction was interrupted before completion and analysed for deuterium content. No 

deuterium incorporation was found either in the substrate or in the styrene. Hence no reversible 

carbanion was formed. The reaction followed E2 path. However, the E1CB mechanism does 

operate in substrates having strong electron- withdrawing groups, e.g., chlorine on b carbon and 

poor leaving groups e.g., fluorine as in Cl2CH-CF3. 

96


10.5. INTRAMOLECULAR ELIMINATION (Ei) 

Concerted 1,2-elimination the base is actually part of the substrate molecule. Such 

elimination can be described as intramolecular. The two groups leave at about the same time and 

bond to each other as they are doing so. The elimination must be syn, for the four and five 

membered transition states, the four or five atoms making up the ring must be coplanar. 

H 

O 

C 

CH 3 

O 

C C 

a 

b 

b 

a 

D 

Syn 

elimination 

a 

b 

C C 

10.5.1. EVIDENCE FOR THE EXISTENCE OF THE Ei MECHANISM 

b 

a 

CH 3CO 2H 

1. The kinetics is first order, so that only one molecule of the substrate is involved in the reaction. 

2. Free-radical inhibitors do not show the reaction. So that, no free-radical mechanism is 

involved. 

3. The mechanism predicts exclusive syn elimination, and this behavior has been found in many 

cases. The evidence is inverse to that for the anti E2mechanism. 

4. C 

14 

isotope effects for the cope elimination show that both the C - H and C - N bonds have 

been exclusively broken in the transition state. 

5. Some of these reactions have been shown to exhibit negative entropies of activation, indicating 

that the molecules are more restricted on geometry in the transition state. 

Examples for Ei Mechanism 

Acetate esters bearing b, hydrogen’s often eliminate acetic acid when pyrolyzed giving 

the corresponding alkenes. This reaction is found to follow a syn stereo chemical course rather 

than anti because the eliminated H must be near double bonded O. 

For this mechanism to operate, the substrate molecule must be able to adopt a cyclic 

conformation (usually five or six), so that the basic atom can approach the b-hydrogen 

within bonding distance because the concerted syn elimination involves a cyclic rearrangement 

of electrons. 

10.5.2. HYDROACYLOXY ELIMINATION 

C 

H 

C 

O 

C 

O 

300 - 550 0 C 

R 

C C 

RCOOH 

97


Ester in which the alkyl group has a b-hydrogen can be pyrolyzed. Most often in the gas 

phase to give the corresponding acid an olefin. 

No solvent is required. For higher olefins a better method is to pyrolyze the alcohol in the 

presence of acetic anhydride. 

The mechanism is Ei. Lactones can be pyrolyzed to give unsaturated acids, provided that 

six membered transition state required for Ei is available. Amides give a similar reaction but 

require higher temperatures. 

10.6. STEREOCHEMISTRY OF ELIMINATION REACTIONS 

Eliminations results in p bond formation. In E2 reaction the p-orbital which develops on 

the a and b carbons with the departure of the leaving group should be parallel for maximum 

overlap, for this both the leaving groups and carbons bearing them should be in one plane. 

When the two leaving groups are planar there are two extreme conformations. Antiperiplanar 

(i.e.) two groups in trans position, syn-periplanar (i.e.) two groups in cis position. The 

elimination then may proceed as given below: 

B: 

R 

B: 

R 

H 

H 

R 

R 

(2) 

R' 

(1) 

R' 

L 

L 

R' 

R' 

H 

R R' 

R 

R 

R 

L 

(1a) 

H 

(2a) 

B: 

R' 

L 

B: 

R' 

R' 

-HL 

-HL 

R 

R' 

R' 

R 

R R 

From the Newman projection of the trans and cis conformations the elimination is 

expected to be more facile from the trans conformation 1(a) than from the cis conformation 2(a). 

This is because in 1(a) the attacking base approaches from the farthest side o the leaving group, 

while in 2(a) the attack is from the same side which causes repulsion. The developing charge on 

the b -carbon displaces the leaving group with its bonding pair from the backside a path of least 

energy. The elimination occurs from the lower energy staggered conformation than from the high 

energy eclipsed conformation. 

R' 

R' 

98


10.7. ELIMINATION VS SUBSTITUTION 

Elimination reactions are usually accompanied by substitution reaction. When the reagent 

is a good base it accepts a proton to yield elimination product and if it is a good nucleophile then 

it attacks the carbon to give substitution product. 

The proportion of elimination and substitution depends upon the following: 

10.7.1. STRUCTURE OF THE SUBSTRATE 

0 

0 

0 

The proportion of elimination increases from 1 ¾¾® 2 ¾¾® 

3 substrates. The reason 

is that alkenes formed on elimination are stabilized by hyperconjucation. The steric strain is 

relieved on the formation of alkene, whereas on substitution the strain is reintroduced. 

10.7.2. NATURE OF THE BASE 

Strong base promotes elimination over substitution and in particular E2 over E1. 

Alcoholic KOH favors elimination and aqueous KOH favors substitution. Strong nucleophiles but 

weak bases promote substitution over elimination whereas strong base but weak nucleophile 

promotes elimination over substitution. Though pyridine and R3N are not strong bases they are 

poor nucleophile because the branching at the nitrogen atom causes steric hindrance to 

nucleophilic attack on carbon. Hence, they act as base to accept the more exposed hydrogens of 

the substituent groups to afford alkene. A similar steric effect is observed with the size of the 

base or nucleophile. Elimination increases with increase in the size of the nucleophile. 

10.7.3. NATURE OF SOLVENT 

A less polar solvent not only favors bimolecular reaction but also E2 over SN2. Change 

of hydroxylic solvents to aprotic solvents increases the base strength as the solvents layer around 

- - - 

the base by hydrogen bonding is absent. Thus Cl , OH , OR etc., are very strong bases in DMF 

or DMSO. The use of aprotic solvent may change the pathway from E1 to E2. 

10.7.4. EFFECT OF TEMPERATURE 

In elimination reaction a strong C-H bond has to break, hence a high activation energy is 

required for elimination reaction rather than for substitution reaction. In general, the proportion 

of elimination increases on using a strong base of high concentration and a solvent of low 

polarity. On the other hand the proportional substitution increases by using a weak base of low 

concentration and a solvent of high polarity. 



Pointed out 

Ø E1 mechanism 

Ø E2 mechanism 

Ø E1CB mechanism 

Ø Ei mechanism 

99


Ø Stereochemistry of elimination reaction 

Ø Elimination vs substitution reaction 


1. How can you distinguish between E1 and E1CB reactions by labeling experiments? 

2. Differentiate E2 and Ei reactions with examples. 


1. With suitable examples, illustrate E1,E2, and E1CB reactions. Outline conditions 

for each of these mechanisms to operate. 

2. What are the stereochemical preferences in elimination reactions? Comment on the 

statement that in contrast to E2 reactions E1 reactions are not stereospecific. 





100


CONTENTS 

LESSON: 11 – TYPICAL ELIMINATION REACTIONS 


11.1. CHUGAEV REACTION 

11.2. COPE REACTION 

11.3. HOFMANN DEGRADATION 







by which the elimination reactions may proceed. 


* learnt possible reaction pathways in typical elimination reactions. 

11.1. CHUGAEV REACTION 

The thermal decomposition of xanthates prepared from alcohols involving stereo specific 

elimination to yield alkenes is called the Chugaev reaction. The reaction is advantageous because 

it requires relatively lower temperature and leads to the predominant formation of unrearranged 

terminal alkenes. 

RCH 2CH 2OH 1. CS 2 / NaOH 

2. CH 3I 

Mechanism: 

R 

O S 

S 

100 - 250 0 C R COS MeSH 

The reaction involves a six membered cyclic transition state, and proceeds through Ei 

mechanistic pathway. 

Me 

Ph 

C C 

H 

Ph 

H 

O S 

S 

Me 

180 0 C 

Syn-elimination 

Me 

Ph 

H 

C C 

S 

H 

O 

Ph 

SMe 

101


MeSH 2 

11.2. COPE REACTION 

COS 

O 

S 

Me 

Me H 

Ph 

cis alkene 

The cleavage of amine oxides to produce an alkene and a hydroxylamine is called cope 

reaction. 

C 

H 

C 

NR 2 

O 

100 - 150 0 C 

C C R 2NOH 

The reaction is usually performed with a mixture of amine and oxidizing agent without 

isolation of the amine oxide. 

The reaction is thus useful for preparation of many olefins. The elimination is a stereo 

selective syn process and the five membered Ei mechanisms operate. 

C 

H 

C 

O 

NR 2 

C C 

H NR2 O 

Evidences indicate that the transition state must be planar. The stereoselectivity of this 

reaction and lack of rearrangement of the product, it is useful for the formation of transcycloolefins. 

11.3. HOFMANN DEGRADATION 

Cleavage of quaternary ammonium hydroxide is the final step of the process known as 

Hofmann degradation. 

Ph 

102


C 

H 

N 

H 

1. MeI 

2. Ag 2O 

C 

NR 3 

OH 

D 

C C NR 3 H 2O 

The reaction is used for synthesizing olefins and some cyclic olefins. 

H 

Me 

CH 3 

1. 2MeI 

2. Ag 2O 

N 

Me 

Me 

OH 

Me 

D 

N C H2 

Me 

H 

OH 

D 

N 

Me 

Me 

+ (CH 3) 3N + H 2O 

The mechanism is usually E2. Hofmann’s rule is generally obeyed by acyclic and 

Zaitsev’s rule by cyclohexyl substrates. Some cases, where the molecules are highly hindered a 

five membered Ei mechanism. 

C 

H 

H 3C 

C 

NR 2 

OH 

C 

H 

C 

:CH 2 

NR 2 

C C 

H NR2 C 

H2 E1and E2mechanisms are distinguished by the use of deuterium labeling. For example, if 

the reaction is carried out on a quaternary hydroxide deuterated on the b-carbon then the 

rate of deuterium indicates the mechanism. If the E2 mechanism is in operation, the 

trimethylamine produced would contain no deuterium. But if the mechanism is Ei the amine 

would contain deuterium. 



Pointed out 

Ø Chugaev reaction 

Ø Cope reaction 

Ø Hofmann degradation 

103



1. Illustrate the mechanism of chugaev reactions with examples. 

2. Explain Cope reaction. 


1. Discuss various factors which influence the extent of elimination and substitution. 

2. Explain the mechanism of Hoffmann degradation. 





104


CONTENTS 



12.2. CARBENES 

12.2.1. STRUCTURE 

12.2.2. GENERATION 

12.2.3. REACTIONS 

12.3. NITRENES 









LESSON: 12 – CARBENES AND NITRENES 

The aim is to motivate and enable a comprehensive knowledge on carbenes and nitrenes. 


* Understood the structure, generation and reactions of carbenes and nitrenes. 


Carbenes are neutral intermediates having bivalent carbon, in which a carbon atom is 

covalently bonded to two other groups and has two valence electrons distributed between two 

non bonding orbital. 

When the two electrons are spin paired the carbons is a singlet, if the spins of the 

electrons are parallel it is a triplet. 

R 

R 

A 

B 

Singlet 

C: 

R 

R R 

Triplet 

R 

105


The nitrenes R - N represent the nitrogen analogs of carbenes and may be generated in 

× × 

the singlet ( R - N or triplet R - N× 

) 

12.2. CARBENES 


A singlet carbene is thought to possess a bent 

2 

electrons occupy the vacant SP orbital. 

A triplet carbene can be either bent 

106 

2 

SP hybrid structure in which the paired 

2 

SP hybrid with an electron in each unoccupied 

orbital or a linear SP hybrid with an electron in each of the unoccupied P-orbital. The singlet 

and triplet state of a carbene display different chemical behavior. Thus addition of singlet 

carbene to olefinic double bonds to form cyclopropane derivatives is much more stereo selective 

than addition of triplet carbenes. 


Carbenes are obtained by thermal or photochemical decomposition of diazoalkanes. 

These can also be obtained by a -elimination of a hydrogen halide from a halo form with base, or 

of a halogen from a gem dihalide with a metal. 

hn 

RCH: N2 RCHN 2 

N 2CHCO 2C 2H 5 

CHCl 3 


B: 

D 

:CHCO 2C 2H 5 

BH :CCl 3 :CCl 2 Cl BH 

These add to carbon double bonds and also to aromatic system and later case the initial 

product rearranges to give ring enlargement products. 

Carbene 

CH 2 

electrocyclic 

rearrangement 

Cycloheptatriene 

When a carbene is generated in a three membered ring allenes are formed by 

rearrangement. 

R 

R 

Br 

Br 

alkylLithium 

R 

R 

RCH=C=CHR 

Allene


12.3. NITRENES 


The nitrenes R - N represent the nitrogen analogs of carbenes and may be generated in 

× × 

the singlet ( R - N or triplet R - N× 

) 


A nitrene can be generated via elimination or by the thermal decomposition of oxides 

( 2 N RN N N N R + ¾® ¾ = = - 

+ - 

R N OSO 2Ar 

H 


) 

base 

R N B H ArSO2O In the chemical behavior, the nitrenes are similar to carbenes; nitrenes get inserted into 

some bonds e.g., C-H bond to give an amide. Aziridines are formed when nitrenes add to C=C 

bonds. 

Insertion 

Addition 

Rearrangements: 

R C N 

O 

R 3CH 

R N R 2C=CR 2 

insertion 

Addition 

R C N 

O 

R 2C 

R 

N 

H 

CR 2 

aziridine 

Alkyl nitrenes do not generally give either of two proceeding reaction because the 

rearrangement is more rapid. 

R 

H 

C N 

H 

RCH=NH 

CR 3 

107


Abstraction: (eg) 

R N R H R N H R 

Dimerization: NH dimerizes to diimide N2H2 

2Ar N Ar N N Ar 

The dimerization is more important for nitrines than carbenes. 



Pointed out 

Ø Structure 

Ø Generation 

Ø Reactions of carbenes and nitrenes 


1. How do you account for the formation of dichloro carbene in the alkaline hydrolysis of 

chloroform? 

2. Why the triplet state of a carbene is more stable than the singlet state? 


1. What are singlet and triplet carbenes? What is the state of their hybridization? Discuss 

various methods available for the generation of carbenes. 

2. Discuss the chemical reactions of nitrenes. 





108


CONTENTS 

UNIT-V 

LESSON: 13 – FREE RADICAL REACTIONS 



13.2. STRUCTURE AND GEOMETRY 

13.4. STABILITY 

13.5. GENERATION OF FREE RADICALS 

13.5.1. THERMAL GENERATION 

13.5.2. PHOTOCHEMICAL GENERATION 

13.5.3. REDOX GENERATION 

13.6. FREE RADICAL SUBSTITUTIONS 

13.6.1. FREE RADICAL SUBSTITUTION MECHANISMS 

13.6.2. SUBSTITUTION BY HALOGEN 

13.6.3. HALOGENATION WITH NBS 

13.6.4. SUBSTITUTION BY OXYGEN 

13.6.4.1. HYDROXYLATION AT AN ALIPHATIC CARBON 

13.6.4.2. HYDROXYLATION OF AN AROMATIC CARBON 

13.6.5. SUBSTITUTION BY SULFUR 

13.6.5.1. CHLOROSULFONATION 

13.6.5.2. FREE RADICAL ADDITION 

13.7. FREE RADICAL ADDITION 

13.8. MOLECULAR REARRANGEMENTS 







by which the free radical reactions may proceed. 

On successful completion of this lesson the student should have learnt possible reaction 

pathways in free radical reactions. 


A covalent bond may get cleaved homolytically to form fragments carrying odd electrons 

which are called free radicals. Free radical intermediates are generally involved in reactions 

which are carried out either at high temperature or under the influence of light. Some reactions 

may proceed even at room temperature via free radical mechanism, particularly in the presence 

of non-polar solvents and in the presence of compounds like peroxides which produce free 

radicals. 

109


O 

C 

O 

benzoyl peroxide 

O 

O C 2 

C O 

O 

benzoyloxy radical 

Free radicals may be electrically charged ions or noncharged species. The common 

characteristic of almost all free radicals is their high chemical reactivity which is due to the 

tendency of electrons to exist in pairs. Free radical is any atom or group that possesses one or 

more unpaired electrons. Elements such as halogen atom (Cl • ) and alkali metal (Na • ) are free 

radicals, since they have odd number of electrons. 

The oxygen molecule contains an even number of electrons (16) but all electrons are not 

paired. Ten of the valence electrons from five pairs, but the remaining two electrons possess 

identical spins. This unusual situation gives oxygen some interesting reactivity characteristic. 

Oxygen is commonly classed as a diradical. 

13.2. STRUCTURE AND GEOMETRY 

O O 

A free radical is a species which has one or more odd electrons. In the species where all 

electrons are paired the total magnetic moment is zero. Since there are one or more unpaired 

electrons, there is a net magnetic movement and the radicals as a result are paramagnetic free 

radicals are usually detected by electron spin resonance. 

Simple alkyl radicals have a planar structure (i.e.) these have SP 2 bonding with the odd 

electron in a p-orbital. The pyramidal structure is another possibility when the bonding may be 

SP 3 and the odd electron is in an SP 3 orbital. The planar structure is in keeping with loss of 

activity when a free radical is generated at a stereo centre. On adding HBr to 2-methyl-1-butane 

in the presence of peroxide, the product has a single stereo centre. However, equal amount of the 

R and S enantiomers are obtained. The product is a racemic mixture. 

H 3C 

H 2 

C C 

CH 3 

CH 2 + HBr 

peroxide 

H 3C 

CH 3 

H 2 

C CH 

110 

CH 2Br 

The carbon atom in the radical intermediate that bears the unpaired electron is planar and 

SP 2 hybridized. This means that the three substituents bonded to it are all in the same plane. R 

and S enantiomers are obtained in equal amounts because HBr has equal access to both sides of 

the achiral radical.


H 3C 

CH 3 

H 2 

C CH HBr 

13.4. STABILITY 

CH 3 H3CH 2C 

CH 3 

C 

H 

CH2Br H 

H3CH2C Racemic mixture 

CH 3 

C 

111 

CH 2Br 

As in the case of carbocations, the stability of free radicals is tertiary > secondary > 

primary and primary and is explained on the basis of hyperconjugation. The stabilizing effects in 

allylic radicals and benzyl radical are due to resonance structures. 

· · 

C6 H 5CH 

3 ¾¾® C6 

H 5CH 

2 + H 

Ease of formation of benzyl radical. 

Bond dissociation energies show that 19 kcal/mol less energy is needed to form the 

benzyl radical from toluene than the formation of methyl radical from methane. The triphenyl 

methyl type radicals are no doubt stabilized by resonance the major cause of their stability is the 

steric hindrance to dimerization. 

C C C 

13.5. GENERATION OF FREE RADICALS 

13.5.1. THERMAL GENERATION 

Homolytic cleavage of sigma bond can be successful with any compound provided the 

temperature is successfully high. Thermal method is useful with selective bonds within a 

molecule which dissociates at temperature below about 200°C. Bonds of peroxy and azo 

compounds have bond dissociation energies below 40kcal /mol and are therefore sufficiently 

weak to be good sources of radicals under typical reaction conditions.


Peroxide R(CO 2) 2 

CN 

H3C C N N CCH3 CH 3 

Me 2C(CN) 

CN 

CH 3 

100-130 

2RCOO 2R + 2CO 2 

H 3C 

2 

Free radicals 

CN 

C 

CH 3 

Stablized radicals 

+ SO 2Cl 2 Me2C(CN)Cl SO 2Cl 

+ 

N N 

In the thermal decomposition of peroxide the reaction involves the fission of the oxygenoxygen 

bond and the initially formed free radical then decarboxylates to give the fragmentation 

products. A fragmentation is thus a process where some initially formed radicals loses a small 

stable molecule. 

13.5.2. PHOTOCHEMICAL GENERATION 

By this method free radicals are formed by sigma bond cleavage 

O 

H 3C C 

CH 3 

Cl 2 

13.5.3. REDOX GENERATION 

h n 

h n 2Cl 

O 

H 3C C 

Acetyl radical 

Chlorine radical 

+ 

CH 3 

Methyl radical 

Free radicals may also be generated by various oxidation- reduction processes. Transfer 

of electron to or from metal atoms and ions is a common method for initiating radical reaction. 

Fe 2+ + H 2O 2 

13.6. FREE RADICAL SUBSTITUTIONS 

Fe 3+ + HO + HO 

112


13.6.1. FREE RADICAL SUBSTITUTION MECHANISMS 

In a free radical substitution reaction 

R - X ¾¾® 

R - Y 

there must first be a cleavage of the substrate RX so that 

may happen by a spontaneous cleavage. 

R 

· · 

- X ¾¾® 

R - X 

113 

· 

R radicals are produced. This 

It may be caused by light or heat or more often, there is actual cleavage, but · 

R is 

produced by an abstraction. 

· 

· 

R - X + W ¾¾® 

R + W - X 

· 

W is produced by adding a compound such as peroxide which spontaneously forms free 

· 

radicals. Such compound is called an initiator. Once R is formed, it may go to product in two 

ways by abstraction. 

R 

· 

+ Y -W 

¾¾® 

R - Y + W 

Coupling with another radical 

R + Y ¾¾® 

R - Y 

· · 

13.6.2. SUBSTITUTION BY HALOGEN 

Initiation 

Propagation 

Halogenation or Halo-de-hydrogenation 

R - H + Cl 

X 

2 

RH 

2 

hg 

¾¾® 2X 

· 

+ X ¾¾® 

R 

hg 

¾¾® 

R - Cl 

Propagation steps for chlorination by t-BuOCl 

· 

· 

· 

· 

R - H + t - BuO ¾¾® 

R + t - BuOH 

R 

· 

+ t - BuOCl ¾¾® 

RCl + t - BuO 

· 

·


CH2-CH3 Br C CH3 Br C 

Ethylbenzene 

Br 2 

hn 

13.6.3. HALOGENATION WITH NBS 

H 

a-bromoethylbenzene 

+ 

(trace) 

Br 

Br 

a,a-dibromoethylbenzene 

The low bond dissociation energy of allylic carbon-hydrogen bonds in free radical 

halogenation. Allylic bromination is carried out with N-Bromosuccinimide in CCl4 in the 

presence of light to avoid addition to double bond. 

Br 

H 

O 

+ N Br 

O 

N-bromosuccinimide (NBS) 

NBS 

O 

N Br 

O 

H Br + 

CCl 4 

h n 

Br Br 

Br 

A Resonance-stabilized 

radical 

+ HBr N H 

O 

O 

Succinimide 

+ 

O 

114 

N H 

O 

Succinimide 

Br Br 

Recycles to continue 

the chain reaction 

+ Br 2


13.6.4. SUBSTITUTION BY OXYGEN 

13.6.4.1. HYDROXYLATION AT AN ALIPHATIC CARBON 

R 3CH 

O 3 

Silica gel 

R 3COOH 

Compounds containing C-H bonds can be oxidized to alcohols. The C-H bond involved is 

tertiary so that the product is a tertiary alcohol. 

13.6.4.2. HYDROXYLATION OF AN AROMATIC CARBON 

ArH + H 2O 2 

FeSO 4 

ArOH 

A mixture of hydrogen peroxide and ferrous sulfate called Fenton’s reagent. 

Fe 2+ + H 2O 2 Fe 3+ + OH HO 

+ 

HO + ArH 

Ar + H2O The rate determining step is formation of 

13.6.5. SUBSTITUTION BY SULFUR 

13.6.5.1. CHLOROSULFONATION 

RH + SO 2 + Cl 2 

· 

HO and not its reaction with the aromatic substrate. 

h n 

RSO 2Cl 

The chlorosulfonation of organic molecules with chlorine and sulphurdioxide is called the reed 

reaction. The mechanism is except that there two additional main propagation steps. 

13.7. FREE RADICAL ADDITION 

R + SO 2 R SO 2 

R SO 2 + Cl 2 R SO2Cl + Cl 

Free radicals add to the common unsaturated grouping to give new radicals. The most 

important of the unsaturated groups in free-radical synthesis is C=C bond, addition to which is 

markedly selective. In particular, addition to the olefins of the type CH2=CHX occurs almost 

exclusively at the methylene group independently of the nature of X. 

115


H 3C 

H 3C 

H 3C 

C 

CH 3 

C 

CH 3 

CH 3 

C 

C 

H 

C 

H 

CH 3 

CH2 + Br H3C C 

Br 

CH 3 

CH 3 

+ Br 

H3C C 

+ Br 

H3C C 

CH 3 

Br 

CH 3 

CH 2 

CH 

Br 

Tertiary radical 

CH 

CH 3 

116 

CH 3 

secondary radical (less stable) 

Three factors seem to control this selectivity. Firstly the steric hindrance between the 

radical and X avoids reaction at substituted carbon atom. Secondly, the grouping X stabilizes the 

radical. Moreover, if X is an alkyl group, the stabilization will result due to hyperconjugation. In 

case however X carries one or more pairs of p-electrons or is an unsaturated group, stabilization 

will be via usual delocalization. 

Addition of HBr to an alkene involves radicals as intermediates; the more stable the 

radical the easier it is to form since the energy barrier is lower for its formation. Thus the 

bromine radical adds to that SP 2 carbon in the alkene that is bonded to most hydrogens to form 

stabler of the two possible free radical. In this reaction peroxide is a radical initiator. 

RO OR 2RO 

RO H Br ROH + Br 

+


CH 3 

CH 2 

H3C C 

+ Br H3C C 

CH 3 

H3C C CH2Br + H Br 

H3C C C Br + Br 

H H2 Thus in the reaction of HBr (absence of peroxide) to an alkene in the absence of 

peroxides the addition is ionic, initiated by the addition of H + to give the most stable carbocation 

(Markovnikov’s addition). 

H 3C C H 

H 3C C H 

+ 

CH2 + HX 

H3C C 

H 

H 

CH 2 

CH 3 

CH 3 

Free radical additions does not obey the Markovnikov's rule 

CH2 + X 

H3C C 

H 

X 

CH 2 

CH 2 

Br 

117 

H 

+ 

(not CH3CH-CH 2) 

- 

X 

(not CH3CH-CH2) - 

Free radical additions "disobey" the Markovnikov's rule 

In the presence of peroxides the addition of HBr to an alkene is initiated by Br to 

produce the most stable free radical (anti Markovnikov’s rule).Peroxide has no effect on the 

addition HCl or HI to an alkene, which, however, occurs according to Markovnikov rule only 

(heterolytic addition). 

1-methylcyclohexene 

+ HBr 

CH 3 

Br 

1-bromo-1-methylcyclohexane 

(Markovnikov's orientation)


1-methylcyclohexene 

+ HBr 

R-O-O-R 

heat 

CH 3 

Br 

1-bromo-2-methylcyclohexane 

(anti - Markovnikov's orientation) 

In a radical reaction, the steps which propagate the chain reaction compete with the steps 

which terminate it. Termination steps are always exothermic since only bond making occurs. 

Thus, only when both propagation steps are exothermic propagation compete with termination. 

When one considers the energetics of the two propagating steps (1 and 2) only for hydrogen 

bromide are both these steps exothermic. For HCl and HI one of these two steps is on the other 

hand endothermic. 

Br C C 

+ C C 

C C 

Br 

DH ° = -3 kcal 

Br 

+ H-Br C C 

DH ° = -6 kcal 

Br H 

1 

Br 

+ 2 

Cl C C + H Cl Cl C C H + Cl 

DH ° = +10 kcal 

endothermic 

I + C C 

I C C 

DH ° = +13 kcal 

endothermic 

(ii) Stereochemistry of radical addition, of hydrogen bromide to alkenes-anti addition 

Br 

2 

1 

118


Radical addition of hydrogen bromide to alkenes is an anti addition. However, such 

stereospecificity, is in contradiction of the sp 2 carbon of the radical which would be rapidly 

rotating (Eq I) with respect to the remainder of the molecule. The observed stereospecificity 

R 

H 

R 

H 

C C 

C C 

H 

R 

H 

R 

+ Br C C 

+ Br C C 

R 

H 

R 

H 

Br 

a bridged 

structure 

Br 

R 

H C C 

rapidly rotating sp 2 carbon of the radical 

H 

R 

R 

H 

H 

R 

C C 

Br 

R 

R 

119 

Br 

Anti addition 

(anti – addition) of the radical addition is explained by invoking the intermediate formation of 

bridged species (Eq II). Evidence for a bromine-bridged radical i.e., a cyclic intermediate comes 

from the fact that the configuration at the chiral carbon (substituted carbon) of optically active 1bromo-2-methylbutane 

was retained during radical substitution. 

Br + C 

Et 

Me 

Et 

H 

Br 

CH 2 

1-bromo-2-methylbutane 

optically active 

Me 

Br 

C CH 2 

a bridged free radical 

retention of configuration 

Br 2 

Me 

Et 

C 

Br 

Et 

Me H 

Br 

Br 

C CH 2 

Br 

CH 2 

1,2-dibromo-2methylbutane 

H 

- HBr 

H 

H


Other data showed that bromination of alkyl bromides gave substitution with high 

regioselectivity, i.e., about 85% at the carbon adjacent to the bromine already present in the 

molecule. This result is surprising, since the positions close to the polar group (e.g., bromine in 

this case) are actually deactivated by the operation of the polar effect. The unusual 

regioselectivity observed in scheme16.17 is the abstraction of hydrogen by Br which is now 

assisted by the bromine already present in the substrate. In fact this unusual abstraction is a 

result of neighboring group participation in a free radical reaction. Moreover, in the case of 

cyclohexenes and its derivatives the formation of trans diaxial addition products (anti addition) 

can be best explained on the basis of a bromine bridged intermediate. 

(H3C) 3C HBr (H3C) 3C 

hn 

Cl 

- 78 

° 

C 

H 

Br 

H 

Cl 

120 

trans - Diaxial addition 

(iii). Addition of Some Carbon Radicals to Alkenes-Formation of Carbon-Carbon Bonds 

The addition of hydrogen bromide to C = C in radical catalysed reactions provides a good 

method of the formation of a carbon halogen bond. Several useful synthetic radical catalysed 

reactions are based on the addition of aliphatic carbon radicals to olefinic bonds. Thus a 

halomethane can be added to an alkene in the presence of peroxides e.g., the addition of 

bromoform to 1-butene. 

PhCOO-OCOPh 

2 PhCO 2 

PhCO 2 + CHBr 3 PhCO 2H + CBr 3 

CH 3CH 2CH=CH 2 

1-butene 

bromoform 

+ CBr 3 CH 3CH 2CH-CH 2CBr 3 

CH3CH2CH-CH 2CBr3 + CHBr3 

CH3CH2CH 2CH2CBr 3 + CBr3 1,1,1-tribromopentane 

One may also use bromotrichloromethane and due to the preferential abstraction of 

bromine (C-Br bond is weaker than C-Cl bond), a trichloromethyl unit is added to the less 

substituted carbon atom of the alkene. 

peroxide 

BrCCl 3 + CH2=CHR Cl3CCH 2CHR 

D 

Other functional groups can also provide sufficient stabilization of radicals to permit 

successful chain additions to alkenes. Acyl readicals are formed by abstraction of the formyl 

- Br


hydrogen from aldehydes and the resulting acyl radicals (R*CO) are stabilized to some extent. 

The chain process results in formation of a ketone by addition of the aldehyde to an alkene. 

CH 3CHO + C 6H 13-CH=CH 2 

peroxide 

C 6H 13-CH 2-CH 2-CO-CH 3 

2-decanone 

Intromolecular addition of a carbon radical to a C=C bone produces a ring. Five 

membered rings are greatly preferred kinetically, even when a five membered ring closure means 

generating a primary radical and a six membered ring closure a secondary radical (This situation 

may be compared with the order of ring formation in intramolecular SN2 reactions : 5>6>3. 

Stability of the ring is not the only factor the probability that the ends can get together is also 

important). Thus five membered rings are readily formed by the tributylstannane method, i.e., on 

reaction of 6-brome-1-hexene with a tributyltin radical. AIBN initiates free radical formation 

from tributyl tin hydride. 

AIBN 

D or hn 

2 

C N 

C N + (Bu) 3Sn-H C N + (Bu) 3Sn 

Br 

+ 

6-bromo-1-hexene 

abstraction of a 

bromine atom 

(Bu) 3Sn-H 

Br 

tributyl tin hydride 

SnBu 3 

methylcyclopentane 

90% 

H 

+ + 

1-hexene 

10% 

cyclization of the 

carbon radical 

121 

(Bu) 3SnBr


H SnBu 3 

BrSnBu 3 

abstraction of a hydrogen methylcyclopentane 

H SnBu 3 

abstraction of a hydrogen 1-hexene 

13.8. MOLECULAR REARRANGEMENTS 

SnBu 3 

122 

H SnBu 3 

Rearrangements which are very common with carbocation intermediates are rare in the 

case of free radicals. In fact the migration of a saturated group is highly unlikely. In the case of 

cationic intermediates migration occurs through a bridged transition state (or intermediate) which 

involves a three center two electron bond. In the case of a free radical there is a third electron in 

the system. It however, cannot occupy the same orbital as the two other electrons. It shall then 

CH 3 

H3C C 

H3C C C H 

+ 

CH 3 

CH 2 + 

the migrationof a methyl group 

CH 3 

H 

CH 3


CH 3 

H3C C CH2 H3C C C H 

CH 3 

have to be in an antibonding level. Consequently the transition state for migration is less 

favorable compared to that in a carbocation. In the case of free radicals, migrations can occur 

with aryl, vinyl, acyl and other unsaturated groups. The migration of an aryl group e.g., involves 

the formation of bridged intermediate by an addition process and the intermediate is a 

cyclohexadienyl radical. 

R 

C C 

C C 

Thus the substrate (I) adds an acyl radical (acyl radicals are formed by the; abstraction of 

the formyl hydrogen from an aldehyde). The free radical (II) formed after phenyl group 

migration then abstracts a hydrogen atom from the aldehyde. 

R 

O 

Ph 

Ph 

RCO 

R 

O 

Ph O Ph 

Ph 

RCHO 

R 

C 

Ph 

C 

Ph 

CH 3 

H 

CH 3 

C 

C 

123 

phenyl group migrates 

Rearrangement 

Ph 

+ RCO 

Migrations have also been observed for chloro groups. Thus in the reaction of (I) with 

bromine in the presence of peroxides a rearrangement to (II) was observed, which was formed 

along with the normal addition product Cl3CCHBrCH2Br. Migration of a halogen could occur 

via a transition state in which the odd electron is accommodated in a vacant d orbital of the 

halogen.


Cl 

Cl C CH = CH2 Cl C CH CH2 Cl 

Cl C C CH2 H 

Cl 


Br 

Cl Br 

Br Cl 

Br 2 


Pointed out 

Ø Structure and geometry of free radicals 

Ø Stability of free radicals 

Ø Generation of free radicals 

Ø Thermal generation 

Ø Photochemical generation 

Ø Redox generation 

Ø Free radical substitutions 

Ø Free radical addition 

Ø Molecular rearrangements 


Cl 

Cl 

Br 

Cl C C CH2 H 

1. Among free radicals, tertiary is more stable. Explain. 

2. How are free radicals generated? 

3. Why in the free radical rearrangement of the vinyl group in (I) to give (III) one involves 

the formation of the intermediate cyclopropyl species? 

HC CH 2 

(H 3C) 2C CH 2 

H 3C 

CH 3 

CH 2 

(I) (II) 

(III) 

4. Predict the radical catalyzed addition of carbon tetra chloride to b-pinene. 


Cl 

Br 

124 

(CH 3) 2CCH 2CH=CH 2 

1. Explain the structure and geometry of free radicals. 

2. Explain the factors affecting the stability of free radicals. 

3. Explain the characteristics of free radical reactions. 

4. Give the detailed account of free radical substitution reaction with mechanism.






125


LESSON: 14 – TYPICAL FREE RADICAL REACTIONS 

CONTENTS 


14.1. SANDMEYER REACTION 

14.2. GOMBERG REACTION 

14.3. PECHMANN REACTION 

14.4. ULLMANN REACTION 

14.5. PSCHORR REACTION 

14.6. HUNSDIECKER REACTION (DECARBOXYLATIVE BROMINE) 







by which the free radical reactions may proceed. 


* learnt possible reaction pathways in typical free radical reactions. 

14.1. SANDMEYER REACTION 

Treatment of diazonium salts with cuprous chloride or bromide leads to aryl chlorides or 

bromides respectively. In either case the reaction is called the Sandmeyer reaction. 

MECHANISM 

ArN 2 + CuCl ArCl 

The mechanism of Sandmeyer reaction is not rigorously known however is believed to 

proceed in the following manner. 

In the first two steps, the arenodiazonium ion species is reduced by Cu (II) salt to give an 

aryl radical species. But two alternative mechanisms are possible for the third step – either the 

resulting Cu (II) salt binds to the aryl radical forming the intermediate Ar–Cu (III) NuX followed 

by its dissociation into Cu (I)X and the substitution product Ar-Nu or the aryl radical reacts with 

the Cu (III) salt giving the substitution product Ar-Nu through ligand transfer and Cu(I) through 

concomitant reduction. 

Ar N 

+1 

N X + CuNu 

Ar N N + 

+2 

CuNuX 

126


Ar + 

APPLICATION 

Examples 

(i) 

(ii) 

(iii) 

Ar N N Ar + N 2 

+1 

Ar Nu + CuX 

+2 

CuNuX Ar 

+3 

CuNuX Ar Nu + CuX 

(intermediate) 

The Sandmeyer reaction is a very useful synthetic tool in organic synthesis. 

NH 2 

NH 2 

O 

NO 2 

NH 2 

NaNO 2 /HCl 

CuCl 

NaNO 2 /HCl 

CuCN 

NaNO 2 /HCl 

KI 

CN 

I 

NO 2 

O 

Cl 

127


(iv) 

(v) 

NH 2 

NH 2 

CH 3 

Br 

14.2. GOMBERG REACTION 

NaNO 2 /HCl 

CuCN 

NaNO 2 /HCl 

KI 

ArH + Ar' N 2 X 

OH 

CN 

I 

Ar-Ar' 

When the normally acidic solution of a diazonium salt is made alkaline, the aryl portion 

of the diazonium salt can couple with another aromatic ring known as Gomberg reaction. 

C 6H 5 N 2Cl 

OH 

C 6H 5 + C 6H 5 NO 2 

+ 

CH 3 

Br 

C 6H 5 N=N-OH C 6H 5 + N 2 OH 

+ 

OH 

p-C 6H 5 -C 6H 4NO 2 + H2O 

It has been performed on several types of aromatic rings and on quinines. 

A FREE RADICAL MECHANISM 

N 2Cl 

14.3. PECHMANN REACTION 

NaOH 

+ NO 2 NO 2 

The acid–catalyzed condensation of phenols with b - ketoesters to produce coumarins is 

called the Pechmann reaction. A variety of condensing reagents such as concentrated sulphuric 

acid, hydrogen fluoride, Lewis acids etc are used. 

128


OH 

MECHANISM 

O 

Michael 

Addition 

R 

O 

O 

H 

+ RCOCH 2COOEt 

R 

O 

H 

OH 

H 

14.4. ULLMANN REACTION 

O 

OEt 

R 

O 

OH 

O 

O 

H 

R 

O 

con H 2SO 4 

- H 2O 

H 

O 

R 

O 

cumarin derivative 

O 

OH 

O 

OEt 

R 

O 

R 

O 

129 

R 

O 

O H 

Ullmann reaction encompasses the synthesis of diphenyl amines, diphenyl ethers and 

diphenyls. 

1. 

C 6H 5NHCOCH 3 + C 6H 5Br + K 2CO 3 

Cu 

Reflux 

(C 6H 5) 2NH + CO 2 + CH 3COOK + KBr 

O 

O


2. 

3. 

Cu 

C6H5OH + C6H5Br + KOH (C 

Reflux 

6H5) 2O + KBr + H2O C6H5NO2 - 

2C6H5I + Cu C6H5 C6H5 + CuI2 D 

2 

The preparation of diaxyls is called Ullmann coupling reaction. 

MECHANISM 

APPLICATIONS 

NO 2 

Cl 

o-nitrochlorobenzene 

I 

Cu 

single electron 

transfer 

I 

Cu 

225 ° C 

(aryl radical) 

diaryl 

NO 2 

O 2N 

2,2'-dinitrobiphenyl 

130 

+ Cu(I)I 

II 

CuI 

+ 

Cu(II)I 2 

(a) A large number of diaryls and polyaryls have synthesized by the Ullmann coupling 

reaction. 

Symmetrical biaryls


2 

HOOC 

I 

Cu 

D 

131 

HOOC COOH 

4,4'-diphenicacid 

(b) Ullmann reaction also provides method for the preparation of diarylamines and diaryl 

ethers. 

Diarylamines 

+ 

COOH 

Cl 

OCH 3 

H2N 14.5. PSCHORR REACTION 

K 2CO 3,Cu 

Reflux 

COOH 

N 

H 

OCH 3 

When the Gomberg–Bachmann Reaction is performed intermolecularly either by alkaline 

solution or with copper powder the procedure is termed Pschorr ring closure. Fluorene is 

prepared starting with o-aminodiphenyl methane. 

CH 2 

NH 2 

o-amino diphenyl methane 

NaNO 2 

H 2SO 4 

The Pschorr synthesis 

CH 2 

N 2 

HSO 4 

Fluorene


MECHANISM 

N O 

2Ar N C 

R 

O 

N-nitrosoamide 

132 

2Ar-N=N-O-COR Ar + Ar-N=N-O + N 2 + R(CO) 2O 

14.6. HUNSDIECKER REACTION (DECARBOXYLATIVE BROMINE) 

This is a free radical substitution reaction, where the reaction of a silver salt of carboxylic 

acid with bromine gives a bromo compound and is a method of decreasing the length of the 

carbon chain by one unit. 

MECHANISM 

RCO 2Ag + Br 2 

Step - 1. RCO 2Ag + Br 2 

Step - 2. R-C-O-Br 

= O 

Step - 3. RCOO 

Step - 4. R + RCOOBr 

CCl 4 

reflux 

RBr + CO 2 + AgBr 

R-C-O-Br + AgBr 

= O 

RCOO + Br 

R + CO 2 

RBr + RCOO 

propagation 

initiation 

The reaction occurs by the formation an acyl hypobromite (Step 1) is not a free radical 

reaction. The acyl hypobromite then undergoes homolysis (Step 2). The acyloxy radical loses 

carbon dioxide (Step 3) and the resulting radical abstracts bromine from a second molecule of the 

hypobromite. 

APPLICATION 

The reaction is of wide scope, producing alkyl and aryl halides. 

(1). CH 3CO 2C(CH 2) 4COOAg 

Br 2 

CCl 4, reflux 

- AgBr 

CH 3O 2C(CH 2) 3CH 2Br


(2). 

(3). 

COOH 

Cl 

COOH 

HgO/light 

Br 2 

HgO, Br 

Br 

Cl 

(80%) 

(4). A free radical has been generated at bridge head position via the Hunsdiecker reaction to 

show that a free radical need not be planar 


Br 

COOAg Br 

Br 2 

CCl 4, reflux 

- AgBr 


Pointed out 

Ø Sandmeyer reaction 

Ø Gomberg reaction 

Ø Pechmann reaction 

Ø Ullmann reaction 

Ø Pschorr reaction 

Ø Hunsdiecker reaction (decarboxylative bromine) 


1. Write the mechanism of Hunsdiecker reaction. 

2. Identify the products formed in the following reaction. 


RCOCH 2COOEt 

Con.H 2SO 4 

1. Explain Sandmeyer’s reaction with mechanism and application. 

2. Give notes on 

(a) Pschorr reaction 

133


(b) Ullmann reaction 

(c) Gomberg reaction 






134


UNIT-VI 

LESSON: 15 – ADDITION REACTIONS 

CONTENTS 



15.1.1. ELECTROPHILIC ADDITION 

15.1.2. NUCLEOPHILIC ADDITION REACTION 

15.2. ADDITION TO DOUBLE AND TRIPLE BONDS 

15.2.1. HYDRATION 

15.2.2. HYDRATION OF TRIPLE BONDS 

15.2.3. HYDROXYLATION 

15.2.4. EPOXIDATION 

15.2.5. MICHAEL REACTION 

15.2.6. HYDROBORATION 







by which the addition reactions may proceed. 


* learnt possible reaction pathways in addition reactions. 


A reaction in which the substrate and the reagent add up to form a product is called 

addition reaction. The reaction occurs at the site of unsaturation in a molecule. Thus, compounds 

having multiple bonds such as 

C C , C C , C O , C N , etc., 

undergo addition reactions. The reactivity of these compounds is due to the more exposed and 

easily available p electrons to the electron-seeking (electrophilic) reagents. 

15.1.1. ELECTROPHILIC ADDITION 

Let us take in general the addition of an acidic reagent, HZ, to an alkene 

135


MECHANISM 

(1) 

(2) 

C C + H:Z C C 

H Z 

C C + H:Z C C 

C C 

. 

H 

+ 

+ :Z 

H 

[HZ = HCl, HBr, HI, H 2SO 4] 

+ 

C C 

H Z 

Step (1) involves transfer of hydrogen ion to the alkene to form a carbonium ion. 

Step (2) is the union of the carbonium ion with base: z. 

+ :Z 

Step (1) is the difficult step and controls the rate of the reaction. This step involves attack 

by an acidic electron - seeking reagent that is an electrophillic reagent and hence is called 

electrophillic addition. 

MECHANISM 

H 3C HC CH 2 

HI 

CH 3 

CH 

I 

CH 3 

136


H 3C HC CH 2 

HI 

CH 3 CH 2 CH 2 

CH 3 CH CH 3 

H3C CH CH3 + I 

CH3 CH 

15.1.2. NUCLEOPHILIC ADDITION REACTION 

Conjugation of electron withdrawing groups activate the carbon-carbon multiple bonds 

towards nucleophillic addition. 

I 

CH 3 

E 

Nu + C C Nu C C Nu C C E 

The substituents reduce the p electron density, thereby aid the attack of the nucleophile 

and stabilize the carbanion formed on attack by delocalization of the negative charge. 

O 

C 

O 

H C 

R 

O 

C 

137 

OR NO 2 

Polar functional groups Eg >C = 0, C º N >C=N, >C=S etc., also undergo nucleophillic 

addition. 

E 

Nu + C O 

Nu C O 

Nu C OE 

Nucleophilic addition to carbonyl group, therefore a characteristic reaction of aldehyde 

and ketones.Considering the steric and electronic factors (inductive effect) of the group attached 

to the carbonyl, carbon, the reactivity of the carbonyl groups decreases in the order:- 

H 2C O RCHO R 2CO ArCHO Ar 2CO


15.2. ADDITION TO DOUBLE AND TRIPLE BONDS 

15.2.1. HYDRATION 

C 

C 

Hg(OAc) 2 

NaBH 4 

Olefins can be hydrated quickly under mild conditions in high yields without 

rearrangement product by the use of oxymer curation. Followed by in situ treatment with sodium 

borohydride. 

H 3C 

CH 2 

CH 3 

2-Methyl-1-Butane 

C CH 2 

Hg(OAc) 2 

NaBH 4 

H 3C 

H 

C 

CH 2 

OH 

C 

OH 

C 

CH 3 

2-Methyl-2-Butananol 

Double bond can be hydrated by treatment with water and acid catalyst. The most 

common catalyst is sulphuric acid. 

The mechanism is electrophilic and begins with attack of proton. The negative attacking species 

may be HSO . 

- 

4 

MECHANISM 

H 

C C + H C C + H 2O 

C C 

OH 2 

_ 

H 

H 

OH 

C C 

138 

CH 3


The addition of water to vinyl ethers causes hydrolysis to aldehydes or ketones. 

C C O + H 2O 

15.2.2. HYDRATION OF TRIPLE BONDS 

C C + H 2O 

HgSO 4 

H 

H 

C C 

C C 

Mercuric ion salts used as catalyst. The addition follows markovnikov’s rule, only 

acetylene gives an aldehyde. 

MECHANISM 

C C + Hg 2+ C C 

H 

C C 

Hg + 

OH 

H 

Hg 2+ 

H 

H 

C C 

H 

OH 

O 

H 2O 

Tauto 

OH 

O 

C C 

Hg + 

H 

OH 2 

C C 

H O 

Carboxylic esters, thiol esters and amides can be made respectively by acid – catalyzed 

hydration of acetylenic ethers, thioethers without a mercuric catalyst. 

139


C C A + H 2O 

H 

H 2C C 

O 

140 

A A=OR,SN,NR 2 

Ordinary electrophilic addition, with the rate determining propitiation as the first step. 

15.2.3. HYDROXYLATION 

C C + OsO 4 

There are many reagents that add two OH group to a double bond. OsO4 and alkaline 

KMnO4 give syn addition, from the less hindered side of the double bond. 

Antihydroxylation can be achieved by treatment with H2O and fumic acid. In this case 

epoxidation occurs first, followed by an SN2 reaction which results in overall antiaddition. 

C C + H2O C C 

H 2O 

OH 

C C 

15.2.4. EPOXIDATION 

OH 2 

_ 

H 

O 

OH 

C C 

H 

OH 

OH 

C 

OH 

C 

H 

O 

C C 

Peroxycarboxylic acids Eg. Per benzoic acid or m-chloro peroxy benzoic acid are used to 

convert alkenes to epoxides. 

Epoxidation is however a stereo specific syn addition. Eg. Cis 2-butene gives only the 

product. Thus it is a concerted process in which the two bonds are formed at the same, formation 

of two bonds at the same time cannot change the stereo chemical relationship of the group in the 

starting alkene.


MECHANISM 

C C + phCOOH 

Evidence for this mechanism is as follows:- 

O 

H 

C 

O_ 

C 

C 

O 

R 

O 

H 

C 

O C 

C C 

1. The reaction is second order. If ionization were the rate – determining step, it would be 

first order in per acid. 

2. The reaction readily takes place in non-polar solvents. 

3. No carbocation character in the transition state. 

4. The addition is stereo specific. 

15.2.5. MICHAEL REACTION 

The base-catalyzed addition of a ‘donar’ compound possessing at least one active 

a-hydrogen atom to an acceptor compound containing an active bond is known as Michael 

reaction. 

CH 2 - EWG + C = C 

(EWG – electron withdrawing group) 

PhCH = CHCOOEt + CH 2(COOEt) 2 

EWG 1 

base 

H 2O 

(i) OEt 

(ii) H 2O 

+ 

O 

R 

O 

C - C 

O 

C 

HC - EWG 

Ph-CH-CH 2COOEt 

CH(COOEt) 2 

The Michael reaction is carried out in a protic solvent (eg: Alcohol) by the use a base. 

EWG 1 

141


142


MECHANISM 

R 3 OOC 

R 2 - CH 

- 

R 2 - C = C - OR 3 

O 

= 

O - 

- 

R 1 O - C - HC = CH - R 

(nucleophilic attack 

at the b-carbon) 

APPLICATION 

(i). 

(ii). 

COOR 3 

COOR 3 

R2 OEt - 

- C 

COOR3 COOR3 O 

= 

C - OR 3 

COOR 3 

(Resonance stabilized 

carbanion) 

O - 

- 

R - CH - CH = C OR ' 

R 2 - C 

- - 

- 

enolate 

The Michael reaction is of great importance in organic synthesis. 

CH 3 - CO - CH2 - COOEt + 

CH - COOEt 

= 

CH - COOEt 

+ CH 2(COOEt) 2 

t-Buok 

COOCH 3 

+ 

R4N Op 

CH 2 - COOEt 

- 

CH - COOEt 

- 

CH - (COOEt) 2 

O 

= 

R - CH - CH 2 -C - OR ' 

R 2 - C 

t-Bu + 

heat 

- - 

COOR3 COOR3 - 

COCH 3 

CHCOOEt 

- 

COOCH 3 

CH 2 - COOH 

- 

CH - COOH 

- 

CH 2 - COOH 

143


15.2.6. HYDROBORATION 

When olefins are treated with borane in ether solvent BH3 adds across the double bond. 

3 - C = C - + BH 3 

Me 

Me 

- 

- 


H 

(- C - C -) 3B 

C = C Me - CH - CH - BH - CH - CH - Me 

Me 

BH 3 


Pointed out 

Ø Electrophilic addition 

Ø Nucleophilic addition reaction 

Ø Addition to double and triple bonds 

Ø Hydration 

Ø Hydration of triple bonds 

Ø Hydroxylation 

Ø Epoxidation 

Ø Michael reaction 

Ø Hydroboration 


Me 

H 

- 

- 

- 

- 

- 

Me 

- 

1. What is addition reaction? Give examples. 

2. How HBr will added to CH2=CH2? 

3. Differentiate hydroxylation and Hydroboration reaction. 

4. What is epoxidation reaction? 


Me 

- 

Disiamylborane 

1. Give mechanism for electrophilic addition reaction. 

2. Give mechanism for nucleophilic addition reaction. 

3. Explain the Michael addition reaction with mechanism and application. 

4. Explain Hydration reactions of double and triple bonds. 


Me 

- 


144





145


LESSON: 16 – ADDITION TO CARBONYL COMPOUNDS 

CONTENTS 


16.1. MANNICH REACTION 

16.2. DIECKMANN REACTION 

16.3. STOBBE CONDENSATION 

16.4. KNOEVENAGEL REACTION 

16.5. DARZEN REACTION 

16.6. WITTIG REACTIONS 

16.7. THORPE REACTION 

16.8. BENZOIN REACTION 







by which the addition reactions of carbonyl compounds may proceed. 


* learnt possible reaction pathways in addition reactions of carbonyl compounds. 

16.1. MANNICH REACTION 

The three component condensation reaction between an active methylene compound, 

formaldehyde and an amine to form a b-amino carbonyl compound (called Mannich base) is 

known as Mannich reaction. 

R 1 CH 2COR 2 + HCHO + HNR 2 

H 

R 

R 

N CH 2 - CHCOR 2 

- R1 

Mannich base 

This is one of the most widely used reactions for the formation of carbon – carbon bonds. 

It is carried out in water, methanol, ethanol or acetic acid. 

Example 

146


O 

+ HCHO + (CH 3) 2NH 

HCl 

CH 3OH 

reflux 

CH 2N(CH 3) 2 

PhCOCH 3 + HCHO + (CH3) 2NH 

HCl 

CH3OH reflux 

PhCOCH 2N(CH3) 2 

MECHANISM 

It is suggested that in the first step, the amine and HCHO in the presence of 

to imminium Cation. 

H 

- 

(i). R2NH + C = O 

R2N - C -OH 

- 

H 

H 

- - H 

H 

O 

147 

+ 

H condense 

R 2N = CH 2 + H 2O 

It is then attached by the enolate anion of the active hydrogen compound in the second 

step from the Mannich base. 

O 

= 

(ii). R ' - C -CH 3 

OH 

- 

R ' - C = CH 2 

APPLICATIONS 

H 

+ CH 2 = NR 2 

OH 

- 

R ' - C = CH 2 

H 

O 

= 

R - C - CH 2 - CH 2 - NR 2 

Many important natural products, especially alkaloids have been synthesized by this 

reaction. 

(1) A classical example is Robinson’s synthesis of tropinone by a double Mannich condensation 

and subsequent synthesis of atropine.


- 

CH 2 

- 

CH 2 

- 

CHO 

CHO 

+ 

H 

- - 

N - Me 

H 

(2) Building up of ring system: 

+ 

HCH 2 

- 

C = O 

- 

HCH 2 

Double 

Mannich 

condensation 

CH 2 

- 

CH 2 

CH 

NMe 

CH 

Tropinone 

CH 2 

CH 2 

The easy elimination of R2NH from Mannich base has synthetic application. 

CH 3COCH 3 + HCHO + (CH 3) 2NH CH 3COCH 2CH 2N(CH 3) 2 

C = O 

CH3I D 

CH 

CH 

3I 

3COCH2CH2N(CH 3) 3I CH3COCH=CH 2 + (CH 

D 

3) 3NHI 

(3) The imminium salt, being a strong electrophile, replaces the active hydrogen of indole, 

phenol, nitroalkane etc., eg. 

(CH 3) 2SO 4 

D 

N 

H 

+ HCHO + (CH 3) 2NH 

N 

H 

16.2. DIECKMANN REACTION 

CH 2N(CH 3) 3 

1. NaCN 

2. H 3O 

N 

H 

Gramine 

N 

H 

b - indole acetic acid 

CH 2N(CH 3) 2 

CH 2COOH 

Intramolecular Claisen condensation in dibasic–acid esters is called Dieckmann reaction. 

The product is cyclic β–ketone derivatives. The condensing bases may be sodium, sodium 

ethoxide, sodium hydride, potassium tertiary butoxide etc. 

MECHANISM 

CH 2COOC 2H 5 

C 

(CH 

2H5ONa 2) n (CH2) n 

CH 2COOC 2H 5 

CH 2 

CH 2 

C=O 

148


The base abstracts a proton from one of the α–carbons. The resulting carbanion then 

attacks the carbonyl carbon of the ester group. Subsequent of the alkoxide ion gives the cyclic 

ketone derivative. 

(CH 2) n 

(CH 2) n 

CH 2COOC 2H 5 

CH 2COOC 2H 5 

CH 2 

C 

CHCOOC 2H 5 

O 

OC 2H 5 

C 2H 5ONa 

APPLICATION AND EXTENSION 

1. Synthesis of various natural products. 

Synthesis of steroid. 

H 3O 

- CO 2 

CH 3 

COOR 

COOR 

CH 2 - CH 2 

- 

CH 3 

2. Preparation of heterocyclic ketoesters: 

C 2H 5ONa 

O 

(CH 2) n 

(CH 2) n 

O 

= 

CH 2COC 2H 5 

CHCOOC 2H 5 

CH 2 

C=O 

CHCOOC 2H 5 

CH 3 

O 

COOR 

149


Piperidone derivative:- 

COOR 

CH2CH2COOR C2H5ONa C2H5N C2H5N O 

H 3O 

- CO 2 

CH 2CH 2COOR 

C 2H 5N O 

1-ethyl-4-piperidone 

3. Extension of the reaction: 

Ziegler applied Dieckmann reaction on dinitriles to obtain large high dilution technique. 

(CH 2) n 

(CH 2) n 

CH 2CN 

CH 2CN 

CHCN 

CH 2 - C = NLi 

C 6H 5NC 2H 5Li 

- C 6H 5NHC 2H 5 

H 3O 

- CO 2 

16.3. STOBBE CONDENSATION 

(CH 2) n 

(CH 2) n 

CH 2 - C 

CH - CNLi 

CH 2 

CH 2 

N 

C=O 

The base catalyzed condensation of aldehydes and ketones with diethyl succinate and its 

derivatives to from monoesters of an α–alkylidene succinic acid is called the Stobbe 

condensation. 

The bases generally used are NaOEt, NaH, KOBu, etc.; one of the ester groups becomes 

hydrolyzed in the course of the reaction. 

150


R 

R 

MECHANISM 

C = O + 

CH 2 - COOEt 

- 

CH 2 - COOEt 

NaOEt 

H 3O 

R 

R 

C = C - COOEt 

- 

CH 2COOH 

The reaction is believed to proceed by initial aldol condensation and subsequent 

intramolecular formation of a lactone intermediate, which then undergoes base – catalyzed 

elimination (E1 or E2) to yield the product. 

CH 2 - COOEt 

- 

CH 2 - COOEt 

Abstraction 

of proton by 

base and ring 

opening 

R 

APPLICATION 

OEt 

R 

R 

R 

O 

O 

H 

CH 2 

OEt 

O = C 

R 

R 

CH - COOEt 

- 

CH 2 - COOEt 

COOEt 

C = C - COOEt 

CH 2COO - 

- 

- OEt 

H 3O 

Aldol 

condensation 

R 

R 

R 

R 

R 

R 

O 

C C COOEt 

O 

O 

H 

CH 2 

C = C - COOEt 

CH 2 - COOH 

- 

CH 2 

C 

O OEt 

COOEt 

Synthetically important cycle ketones can be prepared starting from Stobbe condensation 

product. 

151


p-MeC 6H 4 - C = C 

COOEt 

CH 2COOH 

p-MeC 6H 4 - CH - CH 2 -CH 2 - COOH 

(i i) 

Me 

- 

COOMe 

COOMe 

HBr 

H 2O 

PhCHO, LiOMe, 

MeOH 

CH 2N 2 ether 

16.4. KNOEVENAGEL REACTION 

HF 

ringclosure 

Ph 

p-MeC 6H 4 

Me 

Me 

O 

COOMe 

COOMe 

O 

Me 

O 

152 

(1). NaOH 

(2). CuCr 2O 4/H 2 

(3). H 3O 

Condensation of aldehyde and ketone with compound having active methylene groups in 

the presence of base catalyst to from α,β–unsaturated compounds is called knoevenagel reaction. 

C6H5CHO + H 

Pyridine 

2C(COOR) 2 C6H5CH=C(COOR) 2 

Piperidine 

R 3N 

+ H 2C(COOR) 2 

MECHANISM 

R 3NH + HC(COOR) 2 

1. H 2O 

2. D -CO 2 

C 6H 5CH=CHCOOH 

Cinnamic acid 

The initial stage of the reaction is base catalyzed aldol condensation with dehydration.


O 

R ' C 

H 

+ 

-H 2O 

R 3N 

APPLICATION 

CH(COOR) 2 

+ H 2C(COOR) 2 

R ' -CH=C(COOR) 2 

O 

R - C - CH(COOR) 2 

- - 

H 

1. H 2O/H + 

2. D -CO 2 

R 3NH + HC(COOR) 2 

R 3NH 

- R 3N 

OH 

H 

153 

R-C-CH(COOR) 2 

- - 

R ' -CH=CHCOOH 

1. Various α,β–unsaturated acids such as crotonic, cinnamic and maleic acid can be prepared. 

Piperidine 

CH3CHO + H2C(COOR) 2 CH3CH=C(COOR) 2 

Piperidine 

C6H5CHO + H2C(COOR) 2 C6H5CH=C(COOR) 2 

Piperidine 

HOOC-CHO + H2C(COOR) 2 HOOH-CH=C(COOR) 2 

1. H 2O/H + 

2. D -CO 2 

1. H 2O/H + 

2. D -CO 2 

1. H 2O/H + 

2. D -CO 2 

CH 3CH=CHCOOH 

Crotonic acid 

C 6H 5CH=CHCOOH 

Cinnamic acid 

HOOCCH=CHCOOH 

Maleic acid 

2. By reacting aldehyde with active methylene compound in 1:2 molar proportions, various 

dibasic acids and diketones can be prepared.


R - CHO + 

H 2C 

H 2C 

16.5. DARZEN REACTION 

COOCH 3 

COOEt 

COOCH 3 

COOEt 

Acid 

hydrolysis 

Ketonic 

hydrolysis 

Piperidine 

R-HC 

CH2COOH R-CH 

CH2COOH 3-alkyl glutaric acid 

R-CH 

CH 2COCH 3 

CH 2COCH 3 

4-alkyl-heptan-2,6-dione 

HC 

HC 

COOCH 3 

COOEt 

COOCH 3 

COOEt 

Aldehydes and ketones condense with α–halo esters in the presence of bases to given α,β– 

epoxy esters called glycidic esters. This is called Darzen’s condensation. 

C 

O 

+ 

MECHANISM 

Cl CH COOEt 

R 

NaOEt 

R 

C C 

O 

COOEt 

The reaction consists of an initial knoevenagel type condensation followed by an SN2 

reaction. 

C 

O 

+ Cl CH COOEt 

R 

C C 

O 

R 

COOEt 

NaOEt 

Cl 

C C 

|O| R 

COOEt 

154


Sodium ethoxide is often used as the base, although other bases, including sodium amide 

one sometimes used. 

APPLICATION 

The formation of epoxides from aldehydes and ketones. 

C 

O 

16.6. WITTIG REACTIONS 

+ 

Me2 S CH2 C O 

O 

Witting reaction affords an important and useful method for the synthesis of alkenes by 

the treatment of aldhydes or ketones with alkylidenetriphenyl phosphorane (Ph3P=CR2). 

Ph 3P = CH 2 + Ph 2C = O Ph 2C = CH 2 + Ph 3P = O 

MECHANISM 

The reaction probably proceeds by the nucleophillic attack of the yield on the carbonyl 

carbon. The dipolar complex so formed decomposes to keyton and triphenylphosphin oxide via a 

four centered transition state. 

Ph 3P - CR 2 

+ 

O = CR'R" 

Ph 3P - CR 2 

- 

O - CR'R" 

Betain 

Ph 3P 

O 

CR 2 

CR'R" 

C 

H 2 

Ph 3P 

O 

CR 2 

+ 

CR'R" 

The mechanism is supported by the fact then an optically active phosphonium salt reacts 

to produce a phosphonium oxide with retention of configuration. 

Et 

P CH3Br Ph 

PhH2C APPLICATION 

C 6H 5Li 

Et 

P 

Ph 

PhH2C CH 2 

1. Formation of exocyclic methylene group. 

C6H5CHO C6H5CH = CH2 + 

Et 

Ph 

PhH2C P 

155 

O + Ph 3P - CH 2 CH 2 Ph 3P = O 

+ 

Cyclohexanone Methylene cyclohexane 

O


2. Preparation of b, g unsaturated acids. 

R 2C = O + Ph 3P - CH - CH 2COO R 2C = CHCH 2COO + Ph 3P = O 

3. Preparation of natural products. 

CH - PPh 3 

+ OHC 

1 2 3 4 5 6 7 8 9 

b-carotene 

4. Formation of large rings containing 5 to 16 rings. 

R - C = O 

(CH 2) n 

16.7. THORPE REACTION 

CHO 

R - C - PPh 3 R C 

CR' + Ph3P = O 

(CH 2) n 

In the Thorpe reaction, the α–carbon of one nitrile molecule adds to the CN carbon of 

another molecule. The C=NH bond that result can be hydrolyzed to get β–keto nitriles. 

MECHANISM 

H 

H3C C C N 

H 

base 

- H + 

H 3C 

H 

C 

C N 

156


H 

H3C C C N 

H 

CH 3 CH 2 C 

CN 

CHCH 3 

NH 

imino-nitrile 

CH 3 

CH 

CN 

16.8. BENZOIN REACTION 

H 2O 

CH3 CH 2 C 

N 

CH 3 CH 2 C 

CN 

CH CH 3 

O 

CH 3 

CH 

H 2O 

CN + NH 3 

This reaction id the cyanide ion catalyzed intermolecular condensation of an aromatic 

aldehyde to give an alyloin. The condensation of benzaldhyde gives benzoin. 

MECHANISM 

C 6H 5 

O 

C 

H 

C 6H 5CHO 

- CN 

APPLICATIONS 

2C6H5CHO benzaldehyde 

KCN 

O 

CN C 6H 5 C 

C 6H 5 

C 6H 5 

O 

C 

OH 

C 

CN 

O 

C 

H 

OH 

C 

H 

H 

C6H5CHOHCOC 6H5 benzoin 

CN C 6H 5 C 

C 6H 5 C 6H 5 C 

C 6H 5 

Benzoin condensation can be accomplished for glyoxals also 

O 

CN 

OH 

C 

H 

OH 

157 

CN 

C 6H 5


CHO 

CHO 

+ 

CHO 

CHO 

ethanolic KCN 

reflux 

The crossed benzoin condensation using glyoxals may be applied for synthesis of 

polynuclear hydrocarbons. 

2. Heterocyclic aldehydes also undergo benzoin condensation reaction. 

2 

O 



Pointed out 

CHO 

Ø Mannich reaction 

Ø Dieckmann reaction 

Ø Stobbe condensation 

Ø Knoevenagel reaction 

Ø Darzen reaction 

Ø Wittig reactions 

Ø Thorpe reaction 

Ø Benzoin reaction 


ethanolic 

KCN 

1. Give the products formed and mechanisms of the reactions. 

O 

O 

O 

OH 

OH 

OH 

O 

O 

OH 

OH 

O 

158


(a) 

C 

O 

Cl 

H 

C 

(b) 2C KCN 

6H5CHO 2. Differentiate Thorpe and Wittig reactions. 


1. Describe Mannich reaction with mechanism. 

2. Explain with mechanism and applications of 

(a) Stobbe condensation 

(b) Knoevenagel reaction 


R 

COOEt 

NaOEt 





159


UNIT-VII 

LESSON: 17 – CONCERTED REACTIONS: PERICYCLIC REACTIONS 

CONTENTS 



17.2. ELECTROCYCLIC REACTIONS 

17.2.1. THERMAL CYCLIZATION OF BUTADIENES 

17.2.2. THERMAL RING OPENING OF CYCLOBUTENES 

17.2.3. PHOTOCHEMICAL INTERCONVERSION OF 3,4-DIMETHYLCYCLO- 

-BUTENE AND 2,4-HEXADIENE 

17.2.4. OPENING OF A 1,3-CYCLOHEXADIENE AND RING CLOSURE 

17.3. GENERALISED WOODWARD-HOFFMANN RULE 

17.4. CYCLOADDITION REACTIONS: CORRELATION DIAGRAM AND FRONTIER 

MOLECULAR ORBITAL METHOD 

17.5. STEREOCHEMICAL MODES OF CYCLOADDITION: SUPRAFACIAL AND 

ANTARAFACIAL PROCESSES 

17.6. ORBITAL SYMMETRY IN CYCLOADDITION REACTION: CORRELATION 

DIAGRAMS 

17.7. FRONTIER MOLECULAR ORBITAL (FMO) METHOD 

17.8 CYCLOADDITIONS 

17.8.1. DIELS-ALDER REACTIONS 

17.8.2. [2+2] CYCLOADDITIONS 

17.9. 1, 3-DIPOLAR CYCLOADDITIONS 

17.10. CHELETROPIC REACTIONS 

17.11. SIGMATROPIC REARRANGEMENTS 

17.11.1. SIGMATROPIC MIGRATION OF HYDROGEN 

17.11.2. SIGMATROPIC MIGRATIONS OF CARBON 

17.11.3. THE COPE REARRANGEMENT 

17.11.4. THE CLAISEN REARRANGEMENT 

17.11.5. THE DI-PI-METHANE REARRANGEMENT 







by which the pericyclic reactions may proceed. 


* learnt possible reaction pathways concerted reactions Woodward-Hofmann rules and 

organic photochemistry. 

160



In a pericyclic reaction, there is concerted bond reorganization and the essential bonding 

changes occur within a cyclic array of the participating atomic centers. These reactions do not 

involve the intermediate formation of either ions or radicals. Pericyclic reactions are also largely 

unaffected by polar reagents, solvent changes, radical initiators etc. These can however, be 

influenced only thermally or photochemically. 

LUMO 

HOMO 

ethylene 

E 

y 4 

LUMO 

y 3 

HOMO 

y 2 

y 1 

The molecular orbitals of 1,3-butadiene 

(Scheme 17.1) 

Antibonding 

Bonding 

A consideration of the phase of orbitals (Schemes 17.1.1 and 17.1.2) has significance, 

since only orbitals of the same phase will overlap to result in bonding. The orbitals of the 

different phase lead to a repulsive anti-bonding situation. 

161


E 

A 1,3,5-hexatriene. Configuration of p electrons in the ground 

state and the first excited state 

(Scheme 17.1.2) 

y 6 

y 5 

y 4 

y 3 

y 2 

y 1 

Antibonding 

HOMO 

Bonding 

A reasonable way to understand the outcome of pericyclic reactions is by the use of 

frontier orbital approach. Here the electrons in the highest occupied molecular orbital (HOMO) 

of one reactant are taken as being similar to the outer valance electrons of an atom. The reaction 

then involves the overlap between the HOMO orbital (a potential electron donor) with LUMO, 

(the lowest unoccupied molecular orbital – a potential electron acceptor of the other reactant). 

17.2. ELECTROCYCLIC REACTIONS 

These are pericyclic reactions (intramolecular) which under the influence of heat or light 

involve either the formation of a ring, with the generation of one new sigma-bond and the 

consumption of one pi-bond or the reverse (Scheme 17.2.1). 

162


1,3,5-hexatriene 1,3-cyclohexadiene cyclobutene 

1,3-butadiene 

(Scheme 17.2.1) 

The stereochemistry of electrocyclic reactions can be studied by using suitably 

substituted molecules (Scheme 17.2.2). The reactions are thus: 

1. Completely stereoselective. (A stereoselective reaction leads to the exclusive 

formation of one of the several possible stereoisomeric compounds. The reaction is solely 

concerned with the products). 

Me 

H 

H 

Me 

trans,cis,trans-2,4,6- 

Octatriene 

Me 

H 

Me 

H 

trans,cis,cis-2,4,6- 

Octatriene 

Me 

H 

H 

Me 

heat 

heat 

hn 

Me 

H 

H 

Me 

(I) 

cis-5,6-dimethyl-1,3-cyclohexadiene 

Me 

H 

Me 

H 

(II) 

trans-5,6-dimethyl-1,3-cyclohexadiene 

Me 

heat H 

Me 

H 

cis-3,4-Dimethylcyclobutene cis,trans-2,4-Hexadiene 

(III) 

163


Me 

H 

Me 

H 

Me 

heat H 

Me 

(IV) 

H 

trans-3,4-Dimethylcyclobutene trans,trans-2,4-Hexadiene 

(Scheme 17.2.2) 

2. Electrocyclic reactions are also completely stereospecific (in a stereospecific reaction 

a given isomer gives one product (or d, l pair) while another stereoisomer gives the opposite 

product). 

3. The stereochemical outcome of an electrocyclic reaction depends on the number of 

double bonds in a polyene and on whether the reaction is thermal or photochemical. A thermal 

electrocyclic reaction involving 4 n pi electrons (n=1, 2, 3 ...) proceeds with conrotatory motion 

(i.e., a motion in which the bonds rotate in the same direction) while the photochemical reaction 

involves disrotatory motion (a motion, in which the bonds rotate in opposite directions). 

A thermal reaction involving (4n+2) pi electrons (where n=0, 1, 2...) proceeds with 

disrotatory motion while the photochemical reaction proceeds with conrotatory motion. 

4. The direction taken by an electrocyclic reaction is dependent on the relative stabilities 

of the ring and open-chain reactants. In the case of cyclobutanes e.g., (Scheme 17.2,2, eq III) the 

open chain structure is favored because of the strain in the ring, during the thermal reaction. 

17.2.1. THERMAL CYCLIZATION OF BUTADIENES 

The HOMO of a conjugated diene is y2 (see, Scheme 17.1.1 ). For the bond formation 

the overlap of lobes on C-1 and C-4 of the diene is required. It is only the conrotatory motion 

(Scheme 17.2.1.1, shown in a clockwise way ) which brings the lobes of the same phase together 

for bond formation (In case the conrotatory motion occurs in the opposite, counter clockwise 

direction, even then the lobes of the same phase sign will still overlap as shown in I 

Scheme17.2.1.1). However, the disrotatory motion will bring the lobes of opposite phase 

together and this will be 

Thermal cyclization of a 1,3-butadiene to a cyclobutene 

164


heat 

y 2 (+) (+) 

HOMO for 

thermal reaction conrotatory motion 

165 

(-) (-) or (+) (-) (-) (+) 

(Scheme 17.2.1.1) 

Conrotatory motion allows p-orbital lobes of the same sign to overlap conrotatory motion 

leads to bonding. Disrotatory motion leads to antibonding repulsive and anti bonding. 

Conrotatory motion therefore, explains the observed stereochemistry of the product on thermal 

cyclization of a disubstituted butadiene (eqs III and IV, Scheme 17.2.2) as shown in 

(Scheme 17.2.1.2). 

H 3C 

H3C H 

H 

cis,trans-2,4-Hexadiene 

H 3C 

H 

H 

CH 3 

trans,trans-2,4-Hexadiene 

heat 

conrotatory motion 


CH 3 

(I) 

CH 3 

H 

H 

cis-3,4-dimethylcyclobutene 

CH 3 

heat 

H 

CH3 trans-3,4-dimethylcyclobutene 

Thermal cyclization of substituted butadienes stereochemistry 

indicates conrotatory motion 

(Scheme 17.2.1.2) 

17.2.2. THERMAL RING OPENING OF CYCLOBUTENES 

In keeping with the principle microscopic reversibility the reverse process (Scheme 

17.2.2, eqs III and IV) of thermal ring opening takes exactly the same path. 

Due to conrotatory motion (Scheme 17.2.2.1). A s bond will open so as to give the 

resulting p orbitals which will have the symmetry of the highest occupied p orbital of the 

product. Since in the case of cyclobutenes the HOMO of the product (i.e., a butadiene) in the 

thermal reaction is 

H


y2 therefore, the cyclobutene must open so that on one side the positive lobe lies above the plane, 

while on the other side it is below it. This process also forces the stereochemistry in the product 

from a substituted cyclobutene (Scheme 17.2.2.1). 

CH 3 

H 

p-LUMO 

s-HOMO 

CH 3 

H 

heat 

D 


diene 

HOMO for 

thermal reaction 

H H 

H3C H 

H3C H 

H3C H 

H3C H 

cis-3,4-dimethylcyclobutene cis,trans-2,4-Hexadiene 

conrotatory motion of the methyl groups 

(Scheme 17.2.2.1) 

Trans-3, 4-dimethylcyclobutene can undergo conrotatory ring opening which could in 

principle give two products (Scheme 17.2.2.2) depending on the sense of conrotation. When 

however, both methyl groups turn inwords a severe steric crowding would result in the formation 

of cis-cis-dimethyldiene. This process will raise the activation energy compared with the process 

of formation of trans, trans-isomer. As a result only the trans, trans-isomer is formed. 

H 

H 

CH 3 

CH 3 

CH 3 

H 

CH 3 

H 

heat 

conrotatory 

heat 

conrotatory 

trans-3,4-Dimethylcyclobutene 

H 

H 3C 

(Scheme 17.2.2.2) 

CH 3 

H 

H 

CH 3 

trans-trans-2,4-Hexadiene 

E,E-hexa-2,4-diene 

H 3C 

H 

cis,cis--2,4-Hexadiene 

Z,Z-hexa-2,4-diene 

(not formed) 

166


17.2.3. PHOTOCHEMICAL INTERCONVERSION OF 3,4-DIMETHYLCYCLO- 

-BUTENE AND 2,4-HEXADIENE 

This photochemical interconversion tends to lie over in favor of the cyclobutene. The 

irradiation of the diene will lead to the promotion of an electron into the orbital of next higher 

energy level i.e., y3 and consequently the HOMO to be considered now is y3 (see, Scheme 

17.1.1). It is now the disrotatory motion, which results in bonding situation (Scheme 17.2.3.1). 

Similarly, the reverse reaction also involves a disrotatory motion, which establishes the 

stereochemistry on suitably substituted substrates (Scheme 17.2.3.2). 

CH 3 

H 

y 3* 

(HOMO) 

conjugated diene 

Disrotatory motion 

CH 3 

H 

disrotatory motion 

cis-3,4-dimethylcyclobutene 

Highest occupied 

molecular orbital of 

the first excited state 

hn 

(Scheme 17.2.3.1) 

H 

(-) (+) (+) (-) 

H H 

167 

H3C H CH H 

3 

3C 

H CH3 (Scheme 17.2.3.2) 

H 

trans,trans-2,4-Hexadiene 

The stereochemical outcome of these reactions thus depends on the relative phase of the 

lobes at the terminal carbon atoms of the molecular orbitals of these systems (see, Scheme 

17.1.1). Two such terminal lobes with the same phase (in the HOMO after irradiation, y3 of the 

diene with 4p electrons) require disrotatory movement for bond making/bond-breaking process. 

On the other hand two terminal lobes with opposite phases (as in the HOMO y2 of the diene with 

4p electrons) have to undergo conrotatory movement for bond-making / bond-breaking process. 

17.2.4. OPENING OF A 1,3-CYCLOHEXADIENE AND RING CLOSURE 

The HOMO for the ground state of a hexatriene is y3 and when compared with the 

HOMO of the ground state of butadiene i.e., y2 one finds that the relative symmetry about the 

terminal carbons is opposite (see, (Scheme 17.2.4.1 and 17.2.4.2). Thus unlike the thermal 

opening of a 1, 3-cyclo-hexadiene and likewise the ring closure requires a disrotatory motion. 

Based on these arguments trans, cis, trans -2, 4, 3-octatriene gives specifically cis-5, 6-dimethylcyclohexadiene 

(Scheme 17.2.4.1). Similarly, for the reverse reaction, since the positive lobes 

must lie on the same side of the plane (consider y3 i.e., HOMO of a triene) a disrotatory motion 

has to occur (Scheme 17.2).


CH 3 

H 

H 

CH 3 

trans,cis,trans-2,4,6-Octatriene 

- 

CH 3 

H 

CH 3 

(+) (+) - 

H 

heat 


leads to bonding 

interaction 

heat 

cis-5,6-dimethyl 1,3-cyclohexadiene 

(Scheme 17.2.4.1) 

H 3C 

H H 

CH 3 

H 

H 

CH 3 

CH 3 

cis-5,6-dimethyl 1,3-cyclohexadiene 

CH 3 


(Scheme 17.2.4.2) 

H 3C 

H H 

H 

CH 3 

H 

168 

CH 3 

trans,cis,trans-2,4,6-Octatriene 

In the excited state of hexatriene y4 is the HOMO (irradiation results in the promotion of 

an electron into the orbital of the next higher energy level). Therefore, the photochemical 

opening of a 1,3-cyclohexadiene, and likewise, the ring closure require conrotatory motion 

(Scheme 17.2.4.3). Thus e.g., the ring cleavage of trans-5, 6-dimethyl-1,3-cyclohexadiene 

proceeds as shown (Scheme 17.2.4.4) 

- 

CH 3 

H 

Disrotatory 

The HOMO for the ground state 

of the hexatriene is y 3 

H 

(+) (+) - 

CH 3 

Conrotatory 

Bonding Bonding 


leads to bonding 

interaction 

hn 

H 3C 

trans-5,6-dimethyl 1,3-cyclohexadiene 

(Scheme 17.2.4.3) 

H H 

In the excited state of the hexatriene, 

y 4 is the HOMO 

CH 3 

(Scheme 17.2.4.4) 

H 3C 

H H 

CH 3 

trans,cis,trans-2,4,6-Octatriene


17.3. GENERALISED WOODWARD-HOFFMANN RULE 

The above observations lead to the prediction that the reacting p-systems with a total 

number of 4q + 2 electrons (2, 6.10 etc) undergo thermal (s,s) cycloaddition while those with 4q 

electrons (4.8 etc.) undergo thermal (s,a) and photochemical (s,s) cycloaddition. They conform 

to the generalized Woodward-Hoffmann rule which states that a ground state pericyclic change is 

symmetry allowed (and so facile) when the total number of (4n +3) s and (4n) a components (say, 

X and Y respectively) is odd. Thus in the cycloaddition of butadiene and ethylene, ethylene 

serves as the (4n +2) s component and butadiene as the (4n) s component, i.e., X=1 and Y=0 

making the total odd and the thermal ground state addition is symmetry allowed. A few relevant 

points emerge from the above discussion: 

(i) For a two component cycloaddition, the maximum number of modes of addition is 2 2 

(for n components, it is 2 n ): (s,s),(s,a),(a,s), and (a,a). 

(ii) Only in the (s,s) mode of addition, the two p-systems approach in parallel planes. In all 

other modes of addition, the components approach orthogonally. 

(iii) Configuration of groups at the two termini of a suprafacial component is retained while 

that on an antarafacial component is inverted. 

(iv) For either m or n greater than 2, there are two modes of (s,s)-additions, the substitution 

pattern permitting, one giving endo product and the other giving exo product (to be 

illustrated later). 

(v) The [p4s+p2s] addition is most facile closely followed by [p4a+p2a] addition. 

17.4. CYCLOADDITION REACTIONS: CORRELATION DIAGRAM AND FRONTIER 

MOLECULAR ORBITAL METHOD 

The most familiar example of a cycloaddition reaction is the Diels-Alder reaction which 

involves the formation of a cyclic compound from an alkene and a diene. 

These reactions consist in the addition of a system of m p electrons to a system of n p 

electrons thereby forming a cyclic product. They offer a versatile route to the synthesis of cyclic 

compounds with a high degree of stereo-selectivity under thermal and photochemical conditions. 

Depending upon the number of p electrons participating in the process, these reactions are 

termed (m+n) or (m+n+.....) cycloaddition reactions. 

1. 

2. 

2+2 Cycloaddition 


169


3. 

C C 

O O O 

C O 

O 

NC 

4. C C 

CN 

NC CN 

C O 

NC 

NC 


CN 

CN 

2+2+2 

Cycloaddition 

17.5. STEREOCHEMICAL MODES OF CYCLOADDITION: SUPRAFACIAL AND 

ANTARAFACIAL PROCESSES 

Since in a typical cycloaddition reaction, there is addition of two systems containing 

double bonds, it is logical to expect the addition to occur on the same or the opposite side of the 

system. Furthermore, as both the p systems are undergoing addition, it is necessary to specify 

these modes of addition on each of them. These different modes have been termed suprafacial 

(on the same side) and antarafacial (on the opposite side). 

C C C C 

suprafacial antarafacial 

This specification is usually made by placing a suitable subscript (s or a) after the number 

referring to the pi component. The Diels-Alder reaction may be considered as a process 

involving 2s+4s cycloaddition. 

R 

H 

H H 

C C 

H 

H H 

R 

R 

H H 

R 

(2s + 4s) 

170


17.6. ORBITAL SYMMETRY IN CYCLOADDITION REACTION: CORRELATION 

DIAGRAMS 

To illustrate the control of orbital symmetry on cycloaddition reactions, we choose the 

simplest example in which the two ethylene molecules approach each other vertically (2s+2s) to 

H 

H 

H H 

H 

1 

H 

H H 

2 

form a molecule of cyclobutane. Such a system has vertical and horizontal planes of symmetry 

which shall be referred to as 1 and 2, respectively. 

In the above transformation we are mainly concerned with the four p orbitals of the two 

ethylene molecules and the four s orbitals of cyclobutane. 

2 

2 

1 1 1 1 

SS p SA p AS p* AA p* 

1 1 1 1 

SS s AS s SA s* AA s* 

Symmetry properties of interacting ethylene p orbitals and cyclobutane s orbitals 

Fig. 1 

1 

2 

2 

2 

171


The symmetry properties of the remaining orbitals remain unchanged during the reaction 

and need not be considered further. The shapes and symmetry properties of these four p orbitals 

(p,p bonding; p*,p* antibonding) and four s orbitals (s,s bonding; s*,s* antibonding) are listed 

in Fig. 1. The symmetry classifications (SS, SA, AS and AA) are with respect firstly to plane of 

symmetry 1 and then to 2. 

On the basis of the above information, a correlation diagram (Fig. 2) may be drawn in 

which the levels of like symmetry are connected by lines. 

AA p* 

AS p* 

SA p 

SS p 

s 2* AA 

s 1* SA 

s 2 AS 

s 1 SS 

Correlation diagram for cycloaddition and cycloreversion of ethylene-cyclobutane system 

Fig. 2 

A close examination of the diagram leads us to the following two conclusions: 

A. The ground state orbitals of ethylene correlate with an excited state of cyclobutane, 

p 2 p 2 s 1 2 s1 *2 

. Consequently, the combination of two ground state ethylene 

molecules cannot result in the formation of ground state cyclobutane while conserving the 

orbital symmetry. Hence the thermal process is symmetry-forbidden. 

B. As there is correlation between the first excited state of the ethylene system and 

cyclobutane, p2 pp * s 1 2 s2s 1 * , the photochemical process is symmetry-allowed. 

A similar correlation diagram may be constructed for the Diels-Alder reaction which is a 

4s+2s cycloaddition reaction. In this case there is only a single vertical plane of symmetry 

bisecting the carbon framework of two reactants and the product. 

172


E 

y 4 

p * 

y 3 

y 2 

A 

A 

S 

A 

4s + 2s 

S 

S 

p p 

y 1 

S 

Correlation diagram for 4s + 2s cycloaddition 

(Diels-Alder reaction) and the reverse process 

Fig. 3 

A 

S 

A 

A 

S 

s 4 * 

s 3 * 

p * 

s 2 

s 1 

173


In this transformation, we have to consider six orbitals each of the reactants and the 

product. The ground state orbitals of the reactants are y1y2 (of butadiene) and p (of ethylene) 

while y3, p* and y4 are the corresponding antibonding orbitals. Similarly, the ground state 

orbitals of cyclohexene are represented by s1, s2 and p; the remaining three orbitals are 

antibonding. All these orbitals along with their symmetry properties are shown in the correlation 

diagram (Fig. 3). 

It becomes immediately clear from an inspection of the above diagram that there is a 

smooth transformation of the reactant orbitals into the product orbitals. 

y 1 2 p 2 y2 2 

s 1 2 s2 2 p 2 

The Diels-alder reaction (4s+2s cycloaddition) is, therefore, a thermally allowed process. 

On the other hand, photochemical transformation is not possible as the first excited state of the 

reactant does not correlate with the first excited state of the product. Rather it correlates with the 

upper excited state of the product. 

y 1 2 p 2 y2y 3 

s 1 2 s2 2 ps3 * 

Hence there is a symmetry-imposed barrier to photochemical reaction of (4s+2s) type. 

17.7. FRONTIER MOLECULAR ORBITAL (FMO) METHOD 

An alternative approach to determine whether or not a cycloaddition reaction is allowed 

depends upon the symmetry properties of the highest occupied molecular orbital (HOMO) of one 

reactant and the lowest vacant molecular orbital (LVMO) of the other. A favorable interaction is 

possible only when the signs of the coefficients of HOMO and LVMO are the same. In the 

2s+2s cycloaddition of ethylene to form cyclobutane, lobes of HOMO in one molecule and that 

of LVMO in the other do not have corresponding signs and hence the reaction is thermally 

forbidden. Irradiation of ethylene, however, promotes an electron to the antibonding orbital 

which now becomes HOMO and corresponds with the LVMO of the second unexcited ethylene 

molecule. As expected, the combination now proceeds smoothly. 

Ground state 

(D forbidden) 

HOMO 

LVMO 

Excited state 

(hn allowed) 

HOMO of excited 

state 

LVMO of unexcited 

state 

The Diels-Alder reaction may also be analyzed by a similar consideration of the 

molecular orbitals of ethylene and butadiene. 

174


LVMO 

HOMO 

LVMO 

HOMO 

Since signs of the 1.4-lobes of butadiene HOMO match those in the LVMO of ethylene, 

the addition is thermally allowed. 

HOMO 

LVMO 

D allowed 

We reach a similar conclusion by considering the signs of butadiene LVMO and HOMO 

of ethylene. 

LVMO 

HOMO 

D allowed 

No such correspondence is obtained by the irradiation of the reactants and consequently 

the Diels-Alder reaction is a photochemically forbidden process. 

An interesting example of the role of frontier orbitals in determining the product is the 

Diels-Alder reaction of Cyclopentadiene forming dicyclopentadiene. Invariably, the endo dimer 

is formed rather that the exo. This is due to the favorable secondary forces as a result of 

interaction of frontier orbitals of diene and dienophile components which lower the energy of the 

175


transition state. In the following figure (Fig.4) orbitals involved in actual bonding are connected 

by broken lines. An inspection of the transition states reveals that these interactions are present 

in the endo transition state while they are absent in the exo. Thus, the endo transition state for 

this reaction is stabilized vis-a-vis the exo and, therefore, the endo attack should be favored. 

However, in some cases steric factors may be of a greater magnitude than this effect. 

HUMO 

LVMO 

HUMO 

LVMO 

17.8. CYCLOADDITIONS 

endo 

exo 

Orbital interaction in Diels-Alder reaction of Cyclopentadiene 

Fig.4 

The reactions of alkenes (the dienophiles) and polyenes (conjugated dienes) in which two 

molecules react to form a cyclic product, with p electrons being used to form two new s bonds 

are called cycloaddition reactions. These reactions are classified on the basis of p electrons 

involves, in each component, the [4+2] cycloaddition being the well known Diels-Alder reaction 

(Scheme 17.8.1). 

176


Diene 

Alkene 

(dienophile) 

17.8.1. DIELS-ALDER REACTIONS 

cyclohexene 

(Scheme 17.8.1) 

A[4+2] cycloaddition 

Diels-Alder reaction 

These are concerted, thermal [4+2] cycloadditions. A cycloaddition reaction requires only 

heat or light for initiation, radical and ionic intermediates are not involved. A consideration of 

orbital interactions (two combinations) accounts for this (Scheme 17.8.1.1), i.e., the overlap can 

take place between the HOMO of one component and the LUMO of the other and vice versa. In 

either case, the overlap brings together lobes of the same phase. When in the dienophile there is 

conjugation to a group of –M type e.g., carbonyl, nitro etc.,. The reaction occurs under milder 

conditions and gives good yields. The substituent lowers the energy of the LUMO of the 

dienophile so as to bring it closer in energy to the HOMO of the diene. Consequently the bonding 

interactions in the transition in the transition state increases. As expected, the reactivity is also 

increased by an electron releasing group in the diene (Scheme 17.8.1.2). Conversely, when the 

diene contains an electron-withdrawing substituent the dienophile requires an electron-releasing 

substituent for ready reaction. In this situation the interaction is between diene’s LUMO and 

thedienophile’s HOMO. 

HOMO 

y 2 

LUMO 

p * 

[ p 4s+ p 2s] cycloaddition 

(a) (b) 

LUMO 

y 3 

HOMO 

p 

Symmetry - allowed thermal [4+2] cycloaddition: 1,3-butadiene and ethylene 

Overlap of (a) the HOMO of 1,3-butadiene and the LUMO of ethylene, and 

(b) the HOMO of ethylene and the LUMO of 1,3-butadiene. 

(Scheme 17.8.1.1) 

Thus, the bonding at the transition state is more effective when the HOMO of one 

reactant and the LUMO of other are more closely matched in energy. 

177


Me 

Me 

2,3-Dimethyl-1,3butadiene 

O 

H 

Propenal 

200 0 C 

30 0 C 

(Scheme 17.8.1.2) 

Me 

Me 

20% 

100% 

CHO 

As correctly shown (Scheme 17.8.1) the diene reacts in the s-cis conformation, which 

allows the ends of the conjugated system to reach the doubly bonded carbons of the dienophile. 

That the s-cis –geometry of the diene is essential is shown by the unreactive nature of the fixed 

transoid dienes (I and II, Scheme 17.8.1.3). Moreover, as expected the substituents in the dienes 

may also affect the cycloaddition sterically. The substituents affect the equilibrium proportion of 

the diene in the required cisoid form (Scheme 17.8.1.3).Consequently Z alkyl or aryl substituents 

in the 1-position (III, Scheme 17.8.1.3) of the diene slow down the reaction by sterically 

hindering formation of the hindering formation of the cisoid conformation, while bulky 2substituents 

(IV, Scheme 17.8.1.3 ) make it fast. 

2 

3 

1 

4 

cisoid 

(s-cis) 

R 

H 

Required for 

Diels-Alder reaction 

(III) 

transoid 

(s-trans) 

H 

R 

H 

(I) (II) 

R 

(Scheme 17.8.1.3) 

(IV) 

R 

H 

178


Among the useful dienes used in Diels-Alder reaction mention may be made of 

derivatives of hydroxybutadienes. 2-Trimethylsilyloxy-butadiene (I, Scheme 17.8.1.4) react 

easily with dienophiles to give adducts which are enol ethers and these are readily hydrolysed to 

cyclohexanone derivatives. In a modification Danishefsky’s diene (II, Scheme 17.8.1.4) is used 

to enable the formation of s,b-unsaturated compounds. In these examples both the diene and the 

dienophile are unsymmetrical and one expects (see, Scheme 17.8.1.5) regioisomers, however, 

here the regioselectivity is marked. 

O 

O HO 

(H 3C) 3SiO 

OCH 3 

O 

Chlorotrimethylsilane 

(CH 3) 3SiCl 

(H 3C) 3SiO 

(II) 

(CH 3) 3SiCl 

OCH 3 

Danishefsky's diene 

H 3O + 

(Scheme 17.8.1.4) 

(H 3C) 3SiO 

O 

CHO 

(I) 

(H 3C) 3SiO 

O 

O 

OCH 3 

O 

H 3O + 

179 

CHO 

CH 3 

CHO 

CH 3


D 

W W 

D D 

(major product) 

W W 

D D D 

(major product) 

(Scheme 17.8.1.5) 

That the Diels-Alder reaction is concerted (both the new bonds are formed in the same 

transition state is shown by the fact, that it proceeds with retention of configuration of both the 

diene and the dienophile (Scheme 17.8.1.6) i.e., it proceeds stereoselectively syn with respect to 

both the diene and the dienophile as expected of a concerted (supra, supra) mode of addition. 

s-cis Conformation 

of 1,3-butadiene 

CH 3 

CH 3 

H 

H 

H 

H 

COOCH 3 

COOCH 3 

COOCH 3 

COOCH 3 

D 

D 

H 

H 

H 

CH 3 

CH 3 

Diels-Alder reaction is a syn 

addition with respect to both the diene and the dienophile 

(Scheme 17.8.1.6) 

H 

COOCH 3 

COOCH 3 

W 

CH 2OOCH 3 

COOCH 3 

180 

W


The Diels-Alder reaction takes place generally to give the stable endo adduct as the major 

product. For the endo addition e.g., with Cyclopentadiene and maleic anhydride (Scheme 17.8.7), 

the transition state can be stabilized (speeding up the reaction) through secondary interactions. 

O 

O 

O 

Maleic anhydride 

O 

O 

O 

endo Product exo Product 

O 

(Scheme 17.8.1.7) 

These interactions involve the lobes of HOMO and LUMO of the same phase which 

themselves are not involved directly in the formation of bonds. One sees that for the endo 

addition the p system lies more completely over the other. These secondary interactions are not 

possible in the transition state for exo addition since the relevant set of centers in the diene and 

the dienophile are not too far apart, from each other. Attempted preparation of 1,3cyclopentadiene 

by base catalysed loss of HBr from 3-bromocyclopentene (E2 elimination) 

instead gives the endo-Diels-Alder dimer (Scheme 17.8.1.8), by self condensation of the initially 

formed 1,3-cyclopentadiene as the major product. At high temperature, the Diels-Alder reaction 

reverse and the low boiling Cyclopentadiene can be collected and kept at low temperature. 

cyclopentadiene 

D 

(Scheme 17.8.1.8) 

O 

O 

H 

H 

O 

endo-dicyclopentadiene 

An interesting compound triptycene can be prepared by a Diels-Alder reaction between 

benzyne and anthracene (see, Scheme 17.8.1.9). From among pyrrole, furan and thiophene only 

furan undergoes a Diels-Alder reaction. The more stabilized aromatic thiophene, is inert. Pyrrole 

does react with maleic anhydride, but not in Diels-Alder manner. 

O 

181 

O


HOMO p 

LUMO p * 

[p2s + p2s ] 

Symmetry-forbidden thermal 

[2+2] cycloaddition 

i.e., 

D 

cyclobutane 

geometrically possible 

HOMOof 

excited state p * 

LUMO of 

ground state p * 

(Scheme 17.8.1.9) 

[p 2s + p 2s ] 

Symmetry-allowed photochemical 


Cycloaddition of an unsymmetrically substituted diene and an unsymmetrically 

substituted dienophile can lead to regioisomers (Scheme 17.8.1.5). 

One has already seen that in a normal Diels-Alder reaction i.e., between an electron rich 

diene and electron-deficient dienophile, the main interaction is between the HOMO of the diene 

and LUMO of the dienophile (In this situation these orbitals are more closely matched in energy, 

the better is the overlap and thus the reaction occurs more readily). However, the orientation of 

the product from an unsymmetrical diene and an unsymmetrical dienophile depends mostly on 

the atomic orbital coefficients at the reacting termini. The atoms with the larger terminal 

coefficients on each reactant, bond preferentially in the transition state, because of better orbital 

overlap. Consequently with 1-substituted butadienes the major product is 1,2 (“ortho”) adduct 

while with 2-substituted butadienes, the major adduct is 1,4 (“para”). 

In the case of butadiene-1 carboxylic acid and acrylic acid the frontier orbitals are 

polarized as shown (Scheme 17.8.1.10). The size of the circles as shown is roughly proportional 

to the size of the coefficients and an allowed reaction leads to 1, 2-adduct. Similarly, now with 

2-phenyl-butadiene and methyl acrylate the major product formed would be 1,4. 

CO 2H 

HOMO LUMO 

CO 2H 

CO 2H 

CO 2H 

182


C 6H 5 

CO 2Me 

HOMO LUMO 

(Scheme 17.8.1.10) 

C 6H 5 

CO 2Me 

Some Diels-Alder reactions are catalysed by Lewis acid catalysts. These catalysts form 

complexes with the polar groups on the dienophile which lower the energies of the frontier 

orbitals of the dienophile. Consequently, the energy difference between the HOMO of the diene 

and the LUMO of dienophile is reduced and the reaction becomes faster. 

17.8.2. [2+2] CYCLOADDITIONS 

In the dimerization of ethylene, a thermal [2+2] cyclization would involve overlap of 

HOMO, p of one molecule with the LUMO, p * of the other (see Scheme 17.1). Now p and p * are 

of opposite symmetry. If in this concerted reaction both bonds to a component are formed on the 

same face i.e., the process is suprafacial, the lobes of opposite phase would approach each other 

(Scheme 17.8.2.1). This interaction which is suprafacial with respect to both components 

(p 2s + p 2s ) is therefore, antibonding and repulsive and the concerted reaction, does not take place 

(symmetry forbidden process). 

HOMO p 

LUMO p * 

[p2s + p2s ] 

Symmetry-forbidden thermal 


i.e., 

D 

cyclobutane 

geometrically possible 

HOMOof 

excited state p * 

LUMO of 

ground state p * 

(Scheme 17.8.2.1) 

[p 2s + p 2s ] 

Symmetry-allowed photochemical 


The photochemical [2+2] cycloadditions which are suprafacial with respect to both the 

components (p 2s + p 2s ) will, however, permit a previously forbidden reaction to become a 

symmetry allowed process. This is so, since here, one has the overlap of the HOMO p * of an 

excited molecule with the LUMO (also p * ) of a ground state molecule (Scheme 17.8.2.1). The 

183


stereochemistry of the Diels-Alder reaction reveals that these are also p 4s + p 2s processes. 

However, a thermal [2+2] cycloaddition could occur provided it is suprafacial with respect to one 

component and antarafacial with respect to the other i.e., it is p 2s + p 2a (Scheme 17.8.2.2). This 

process, though symmetry allowed is geometrically very difficult. 

HOMO p 

LUMO p * 

[p 2s + p 2a ] 

(Scheme 17.8.2.2) 

thermal [2+2] cycloaddition 

symmetry-allowed,but 

geometrically difficult 

Thus the photochemical [2+2] cycloaddition reaction occurs smoothly and represents one 

of the best techniques to synthezise cyclobutane rings and cage compounds (Scheme 17.8.2.3). 

hn 

cyclobutane 

photochemical [2+2] cycloadditions 

Cycloaddition Reactions Stereochemical Rules 

Electron pairs 

(double bonds) 

Even number 

Odd number 

O 

2-Cyclobuhexenone 

Thermal 

reaction 

Antarafacial 

Suprafacial 

hn 

2-Methylpropene 

Photochemical 

reaction 

Suprafacial 

Antarafacial 

O 

H 

H 

184


Br 

OH 

O 

CH 3 

O 

Br 

hn 

hn 

(Scheme 17.8.2.3) 

The reaction can occur inter-or intramolecularly (Scheme 17.8.2.3). Both thermal as well 

as photochemical cycloaddition reactions take place by opposite stereochemical pathways. As 

with electrocyclic reactions one can categorize cycloadditions according to the total number of 

electron pairs (double bonds) taking part in the rearrangement. Thus, a Diels-Alder [4+2] 

reaction between a diene and a dienophile involves an odd number (three) of electron pairs and 

takes place by a ground state suprafacial pathway. A [2+2] reaction between two alkenes 

involves an even number (two) of electron pairs and takes place by a ground-state suprafacial 

pathway. However, it may be impressed that both suprafacial and antarafacial cycloaddition 

pathways are symmetry allowed. Only the geometric constraints inherent in twisting a 

conjugated pi electron system out of planarity make antarafacial reaction geometrically difficult 

in most of the cases. As a last example of cycloaddition, Cyclopentadiene reacts with 

cycloheptatriene system to give a product-which is [6+4] suprafacial process (Scheme 17.8.2.4). 

Cyclopentadiene Cycloheptatrienone 

17.9. 1, 3-DIPOLAR CYCLOADDITIONS 

O 

D 

(Scheme 17.8.2.4) 

These cycloadditions are analogous to the Diels –Alder reaction in that they are concerted 

[p 4s + p 2s ] reactions. The 1, 3- dipolar components are compounds whose representation requires 

ionic structures which include ones with charges on atoms bearing 1, 3-relationship, as in 

Br 

O 

OH 

O 

CH 3 

O 

Br 

185


diazomethane (Scheme 17.9.1). These type of molecules which are called 1, 3-dipoles are 

isoelectronic with allyl anion. These have four p electrons and each has at least one charge 

separated resonance structure with opposite charges in a 1, 3 relationship. The other reactant 

(dipolarophile) in a dipolar cycloaddition has unsaturated bonds like, C = C, C º C, C = O, 

C º N. The 1,3-dipolar cycloadditions form useful reactions for the synthesis of five membered 

heterocyclic rings. 

N N CH 2 

'1,3-dipolar' compound 

diazomethane 

(Scheme 17.9.1) 

N N CH 2 

Mechanistically the transition state for 1,3-dipolar cycloaddition is not high polar and the 

reaction rate is not strongly sensitive to solvent polarity. The loss of charge separation which is 

implied, is more apparent rather than real, since most 1,3-dipolar compounds are not highly 

polar. The polarity associated with a singly structure is balanced by other contributing structures. 

A 1,3 –dipole represents a structural variant of the diene component in the Diels – Alder 

reaction; in the dipolar compound, four p-electrons are distributed over three atoms instead of the 

four in a diene. Moreover, the HOMO and LUMO of a 1, 3-dipole are similar in symmetry to 

that in a diene with respect to the two-fold axis and to the mirror plane which bisects the 

molecule (Scheme 17.9.2), a concerted cycloaddition e.g., to an alkene is a symmetry allowed 

process. The reaction of an alkene with diazomethane to give a pyrazoline (Scheme17.9.3 

pyrazole derivative) belongs to this class. 

1,3-dipolar compound 

1,3-diene 

node 

LUMO HOMO 

CO 2Me 

N N CH 2 

(dipolarophile) 

(Scheme 17.9.2) 

N 

N 

(Scheme 17.9.3) 

CO 2Me 

N 

CO 2Me 

NH 

186


17.10. CHELETROPIC REACTIONS 

In a cheletropic reaction two s bonds that terminate at a single atom are made or broken 

during a concerted reaction (Scheme 17.10.1). In the case of molecules, sulfur dioxide or carbon 

monoxide the HOMO is that which has a lone pair of electrons in the plane having the atoms, 

while the LUMO represents the p orbital perpendicular to this plane (Scheme 17.10.2). 

(a cheletropic reaction) 

SO 2 

(Scheme 17.10.1) 

SO2 

3-sulpholene 

For a symmetry allowed cycloaddition of e.g., SO2 to a diene, the molecule of SO2 must 

lie in a plane which bisects the s-cis conformation of the diene (Scheme 17.10.2). The 

interaction is suprafacial for diene and SO2. In the transition state, the terminal carbon atoms of 

the diene must move in the disrotatory manner in order that the HOMO of SO2 can interact with 

the LUMO of the diene, or the LUMO of SO2 with the HOMO of the diene. 

LUMO 

HOMO 

S 

O O 

LUMO 

S 

O 

O 

sulphur dioxide 

HOMO 

HOMO 

(Scheme 17.10.2) 

LUMO 

C 

O 

carbon monoxide 

S 

O O 

HOMO 

LUMO 

In keeping with these arguments the trans,trans-1, 4-disubstituteed dienes give 

specifically more crowded cis-substituted 3-sulphones (Scheme 17.10.3). From similar 

arguments cis, trans-disubstituted dienes, on the other hand afford trans-substituted-3-sulphones. 

As with electrocyclic reactions, the opposite stereochemistry is observed when the reaction is 

photochemical rather than thermochemical (Scheme 17.10.3). 

187


CH 3 

CH 3 

SO 2 

disrotation 

D 

trans,trans-1,4-disubstituted diene 

CH 3 

CH 3 

SO 2 

hn 

conrotation 

H 

CH 3 

CH 3 

CH 3 

CH 3 

cis,trans-disubstituted diene 

(Scheme 17.10.3) 

3-Sulpholene, a solid, is a convenient substitute for gaseous butadiene. Butadiene is 

generated at high temperatures from 3-sulpholene in a reverse reaction (Scheme 17.10.4) and 

when a dienophile is present it is trapped in a Diels-Alder reaction. The Diels-Alder reaction in 

itself is usually reversible and has been used to protect double bonds. 

SO 2 

3-sulpholene 

D 

ZHC CHZ 

the dienophile 

(Scheme 17.10.4) 

17.11. SIGMATROPIC REARRANGEMENTS 

Sigmatropic rearrangements are pericyclic reactions which involve a concerted 

reorganization of electrons during which a group attached by a s bond migrates to a more distant 

terminus of an adjacent p electron system. There is a simultaneous shift of p-electrons and 

overall, the number of p- and s-electrons remain separately unchanged. These rearrangements 

are described by stating the relationship between the reacting centers in the migrating fragment 

and the p system. The order [i, j] of a sigmatropic rearrangement specifies the number of atoms 

in the migrating fragment and the number of atoms in p-system which are directly involved in the 

bonding changes. Thus the Claisen rearrangement of allyl phenyl ether is a [3,3] sigmatropic 

rearrangement (Scheme 17.11.1) as there is one oxygen atom and two aromatic ring carbons 

between the old and new bond on one side, and three carbons between the old and new bond on 

other. Thus in other words, the numbers set in brackets [I, j] are determined by counting the 

atoms over which each end of the s bond has moved. Each of the original termini is given the 

number 1. 

SO2 

SO 2 

188 

Z 

Z


allyl phenyl ether 

2 

3 

new bond 

1 old bond 

O 

1 

3 

2 

1O 

2 

(Scheme 17.11.1) 

Similarly in the Cope rearrangement (in the 1, 5-heptadienyl system Scheme 17.11.2) 1,5dienes 

isomerizes in a [3,3] sigmatropic rearrangement. In this case a sigma bond moves across 

two parts of a polyene system. 

i 

1 

j 1 

2 

2 

3 

3 

CH 3 

1 

1 

1' 

2 

3 

2' 

3' 

3 

CH 3 

2 

[3,3] 3-methyl-1,5-hexadiene 

Cope rearrangement 

(Scheme 17.11.2) 

In the two examples below (Scheme 17.11.3) in the first the number 1 in the brackets 

indicates that the same atom which was attached to the migration origin now becomes bonded to 

the migration terminus. The number 5 designates migration along the five atoms of the polyene 

system. Similarly in the second case, the migrating group has moved across three atoms of an 

allylic system. 

1 1 

i M 

M 

j 

CH2-CH=CH-CH=CH 2 

CH2=CH-CH=CH-CH 2 

1 2 3 4 5 1 2 3 4 5 

[1,5] 

1 

M 

CH3CH2CH-CH=CHCH 3 

1 2 3 

[1,3] 

(Scheme 17.11.3) 

3 

1 

M 

CH3CH2CH=CH-CHCH 3 

1 2 3 

O 

H 2C 

189 

CH 

CH 2 

H


17.11.1. SIGMATROPIC MIGRATION OF HYDROGEN 

A hydrogen atom is reported to migrate from one end of a system of p bonds to the other, 

under thermal or photochemical rearrangements. In the transition state the hydrogen must be in 

contact with both ends of the chain at the same time. There are two distinct processes by which a 

sigmatropic migration can occur. If the hydrogen moves along the top or bottom face of the psystem 

i.e., migrating group remains associated with the same face of the conjugated system 

throughout the process, the migration is termed suprafacial. When the hydrogen moves across 

the p-system either from top to bottom or vice-versa i.e., the migrating group moves to the 

opposite face of the p-system during the course of migration then it is called antarafacial. 

Ina given sigmatropic rearrangement, the migrating group is bonded to both the migration 

source and the migration termini in the transition state. It is imagined that the migrating H atom 

breaks away from the rest of the system which is treated as a free radical. Thus in a simplest case 

involving a [1,3] shift of hydrogen (Scheme 17.11.1.1). The frontier orbital analysis treats this 

system as a hydrogen atom interacting with an allyl radical. The electron of the hydrogen atom is 

in a 1s orbital which has only one lobe. The HOMO of an allylic free radical depends on the 

number of carbons in the p-framework (Scheme 17.11.1.2). 

H 

H 

Imaginary 


for a [1,3] 

sigmatropic 

rearrangement 

(Scheme 17.11.1.1) 

In the migration of hydrogen the H must move from a plus to plus or from minus to a 

minus lobe of the HOMO, it cannot move to a lobe of opposite sign. Thus the rule predicts that 

antarafacial thermal [1, 3] sigmatropic rearrangements are symmetry allowed (and suprafacial 

pathway is forbidden). 

1 2 3 1 2 3 4 5 1 2 3 4 5 6 7 

The HOMO of the allylic radicals 

(Scheme 17.11.1.2) 

However, such a transition state (I, Scheme 17.11.1.3) would be highly strainged, thus 

antarafacial [1, 3] thermal sigmatropic migrations of hydrogen are unknown. In a photochemical 

reaction promotion of an electron means that now (II, Scheme 17.11.1.3) becomes the HOMO. 

Superfacial pathway for [1,3] shift now becomes an allowed process and antarafacial pathway 

H 

190


forbidden. Thus, the triene (I, Scheme 17.11.1.3) is stable and is not converted by a thermal [1,3] 

sigmatropic rearrangement to toluene a far more stable compound due to an aromatic sextet, 

while the steroid (II, Scheme 17.11.1.3) displays a [1,3] hydrogen shift under photochemical 

conditions. 

(I) 

thermal [1,3] sigmatropic 

migration of hydrogen 

antarafacial migration 

process is allowed 

(I) 

D 

hydrogen atom 1s orbital 

AcO 

CH 3 

H 

(II) 

H 

CH 3 R 

(Scheme 17.11.1.3) 

photochemical 

[1,3] suprafacial 

process 

On the other hand a [1,5] hydrogen shift in a thermal rearrangement being suprafacial 

(Scheme 17.11.1.4), is very common. Heating of indene (Scheme 17.11.1.5) causes the 

scrambling of the label to all the three non-aromatic positions. 

[1,5] hydrogen shift 

suprafacial migration 

process is allowed 

hn 

(II) 

AcO 

H the 1s orbital of a hydrogen atom 

CH 3 

CD 2 

(Scheme 17.11.1.4) 

[1,5]-H shift 

CH 3 

CH 2 

H 

CHD 2 

H 

CH 3 

191 

R


2 

3 

H 

1 

4 

5 

D 

[1,5] 

D 

D 

(Scheme 17.11.1.5) 

It is only via [1,5] shift of H or D (by including the p-orbitals of the benzene ring) that 

one can account for the results. 

In the case of [1,7] hydrogen shifts, in a triene, the orbital symmetry rules predict that the 

transfer of hydrogen must be antarafacial compared to [1,3] shifts, the transition state is not much 

strained and the shift is sterically feasible. This is seen in the thermal Interconversion of vitamin 

D and precalciferol (Scheme 17.11.1.6). 

HO 

CH 2 

Vitamin D 

CH 3 

R 

[1,7]-H shift 

D 

H 

HO 

(Scheme 17.11.1.6) 

17.11.2. SIGMATROPIC MIGRATIONS OF CARBON 

[1,5] 

[1,5] 

H 

D 

CH 3 

Precalciferol 

As compared to a hydrogen atom which has its electrons in a 1s orbital that has only one 

lobe, a carbon free radical (for imaginary transition state) has its odd electron in a p orbital which 

has two lobes of opposite sign. A consideration of the imaginary transition state, shows that if in 

place of hydrogen one has carbon, then during a thermal suprafacial [1,5] process, symmetry can 

be conserved only provided the migrating carbon moves in a manner that the lobe which was 

originally attached to the p system remains attached to it (Scheme 17.11.2.1). The only way for 

this to happen is the retention of configuration within the migrating group. However, a related 

H 

D 

CH 3 

192 

D 

R 

H 

H


[1,3] thermal suprafacial migration would involve opposite lobes. Thus, if the migrating carbon 

was originally bonded via its positive lobe, it must now use its negative lobe to form the new C-C 

bond. The stereochemical outcome of such a process is the inversion of configuration in the 

migrating group. 

a thermal suprafacial [1,5] migration 

configuration is retained 

within the migrating group 

(Scheme 17.11.2.1) 

a thermal suprafacial [1,3] migration 

configuration in the migrating 

group will be inverted 

In summary, a suprafacial [1,5] thermal rearrangement proceeds with retention of 

configuration at the migrating carbon, while the related [1,3] suprafacial process proceeds with 

inversion. 

In the thermal conversion of (I, Scheme 17.11.2.2) to (II) a carbon atom migrates across 

an allyl system, leaving C-1 and ending up at C-3 via a [1, 3] shift. 

3 

bicyclo [3.2.0]-hept-2-ene 

(I) 

2 

C 

1 

[1,3]-shift 

3 

D 

2 

bicyclo [2.2.1]-hept-2-ene 

(II) 

1 

C 

(Scheme 17.11.2.2) 

The results of pyrolysis on (III, (Scheme 17.11.2.3), a trans labeled compound) are in 

keeping with the predicted thermal [1, 3] sigmatropic reaction with inversion at C-7. 

C 

193


H 

AcO 

H 

D 

[1,3]-shift 

C 

H 

D 

AcO 

(III) the transition state 

H 

(Scheme 17.11.2.3) 

Maintenance of bonding overlaps between C-1 and C-3 during the migration (Scheme 

17.11.2.4) involves the following: 

(1) Migration takes place by using the back lobe of the migrating carbon. 

(2) The migrating carbon suffers inversion on reattachment at C-3 of the allyl 

framework. 

(3) To preserve bonding overlaps with C-1 and C-3 rotation must occur and consequently 

the trans-starting material is converted into cis. 

3 

AcO 

2 

H 

C 

1 

D 

3 

AcO 

2 

1 

C D 

rotation 

17.11.3. THE COPE REARRANGEMENT 

3 

C 

AcO 

D 

(Scheme 17.11.2.4) 

1,5-Dienes on heating isomerizes in a [3, 3] sigmatropic rearrangement known as Cope 

rearrangement (see, Scheme 17.11.2). The stereochemical outcome of this rearrangement is in 

keeping with their occurrence through chair-shaped transition states (Scheme 17.11.3.1). 

Meso 3, 4-dimethyl-1,5-hexadiene gives cis,trans-2,6-octadiene (in the starting compound the 

two methyl groups are having cis relationship, in the chair form of a cyclohexane only 1, 2-axial, 

equatorial relationship is cis) while a boat shaped transition state would give trans, trans-or cis, 

cis-product. 

D 

2 

H 

AcO 

1 

H 

AcO 

H 

H 

AcO 

D 

cis 

D 

C 

D 

C 

AcO 

194


H 3C 

H 3C 

meso-3,4-dimethylhexa- 

1,5-diene 

H 3C 

H 3C 

D 

Pyrolysis 

CH 3 

the chair like arrangement 

i.e., 

H 

(Scheme 17.11.3.1) 

CH 3 

cis,trans 

99.7% 

ZE2, 6-octadiene 

(cis,trans isomer) 

The reaction is reversible and gives an equilibrium mixture of the two 1, 5-dienes which 

is richer in the thermodynamically more stable isomer. In the case of 3-hydroxy-1, 5-dienes, 

however, the reaction cannot be reversed, since the 3-hydroxy-1, 5-dienes tautomerize to the 

carbonyl compound ((Scheme 17.11.3.2), oxy-Cope rearrangement). 

CH 3 

H 

CH 3 

HO HO O 

3-hydroxy-1,5-diene 

(Scheme 17.11.3.2) 

Cis-Divinylcyclopropane rapidly undergoes Cope rearrangement to 1, 4-cycloheptadiene. 

Due to unfavorable molecular geometry, the corresponding rearrangement of trans-isomer to 

cycloheptadiene cannot be concerted (Scheme 17.11.3.3) since the ends of the molecule where 

bonding must occur are too far apart. This cis orientation not only provides a favorable geometry 

for interaction of the diene termini so that the loss in entropy in going to the transition state is 

smaller than for an acyclic diene, but the bond being broken is strained and this reduces the 

enthalpy of activation. 

H 

195 

CH 3 

CH 3 

CH 3 

CH 3 

H


H 

H 

cis-1,2-Divinyl - 

cyclopropane 

D 

(Scheme 17.11.3.3) 

1,2-cycloheptadiene 

H 

196 

H 

trans-1,2-Divinyl- cyclopropane 

Divinylcyclopropane rearrangements can proceed even with more ease in case the 

entropy of activation is made still negative by incorporating both vinyl groups into a ring. The 

system then becomes homotropilidene (Scheme 17.11.3.4) which undergoes a degenerat4e cope 

arrangement. A degenerate rearrangement leads to a product which is indistinguishable from the 

reactant. By bridging the two methylene groups in homotropilidene one gets a molecule of 

bullvalene (Scheme 17.11.3.5). This is converted into itself at 25 0 C. At 100 0 C the 1 HNMR 

spectrum of bullvalene shows a singly peak at 4.22 ppm. Bullvalene has a three fold rotational 

axis; thus all the three double bonds are equivalent. The Cope rearrangement is degenerate 

which can occur in each of the three faces of the molecule and is degenerate in every case. 

Bullvalene has a three fold rotational axis; consequently all its three double bonds are equivalent. 

The cope rearrangement can occur in each of the three faces of the molecule and is degenerate in 

every case (Bullvalene is a fluxional molecule- a molecule which undergoes rapid degenerate 

rearrangement). 

bulvalene 

CH 2 

CH 2 

Homotropilidene Still Homotropilidene 

The degenerate Cope rearrangement of homotropilidene 

Cope rearrangement 

(Scheme 17.11.3.4) 

Turn 90 0 

(Scheme 17.11.3.5) 

C 3 

Bulvalene has a 

threefold rotational axis:


17.11.4. THE CLAISEN REARRANGEMENT 

This rearrangement also involves a [3,3] sigmatropic pathway like cope rearrangement, 

however, in Claisen rearrangement the substrates incorporate one or more heteroatoms in place 

of carbon in the 1,5-hexadiene system. The simplest example of Claisen rearrangement is the 

thermal conversion of allyl vinyl ether to 4-pentenal (Scheme 17.11.4.1). The transition state 

involves a cycle of six orbitals and six electrons. With six electrons the transition state has 

aromatic character. Similarly allyl aryl ethers on heating rearrange to o-allyl phenols. 

O 

allylic vinyl ether 

heat O O 

aromatic 


(Scheme 17.11.4.1) 

4-Pentenal 

Studies using migrating groups labeled with 14 C or with substituents show that the allylic 

group is end-interchanged during the ortho rearrangement (Scheme 17.11.4.2). These and other 

results which show that the Claisen rearrangement is intramolecular provide strong support for a 

concerted mechanism. When both o-positions are filled the allyl group migrates to the p-position 

(Scheme 17.11.4.3). 

O 

H 2 

* C 

Allyl aryl ether 

CH 3 

OCH 

CH 

CH 2 

C 

H 

D 

CH 2 

O 

H 2 

C 

H 

C 

H 

* 

CH2 OH 

allyl group normally migrates to the ortho position 

(the allylic group is end-interchanged) 

D 

OH 

(Scheme 17.11.4.2) 

CH 2CH CHCH 3 

the Claisen rearrangement 

197 

CH 

* 

2CH CH2


H 3C 

H 3C 

OCH 2=CHCH 3 

H 3C 

CH 3 

O 

heat 

Claisen rearrangement 

CH 3 

CH 

CH 2 

CH 3 

CH 

H 3C 

If both ortho positions are blocked, rearrangement to 

the para position takes place 

O 

CH 3 

H CH 2CH=CCHCH 3 

(Scheme 17.11.4.3) 

H 3C 

O 

CH 3 

CH 

H 2C 

CH 3 

CH 

Two successive allylic 

rearrangements restore 

the original orientation 

of the allylic group 

OH 

CH 3 

CH 2CH=CCHCH 3 

In a [3, 2]-sigmatropic rearrangement, the reactants have a two-atom migrating unit where 

one atom has a negative charge; this is equivalent to the two p-electrons of an unsaturated bond 

in a three-atom moiety. The rearrangements of allylic sulfoxides, selenoxides and amine oxides 

are examples. Thus in the Sommelet rearrangement the two-atom unit is a nitrogen 

ylide -NR 2-CH 2. 

17.11.5. DI-PI-METHANE REARRANGEMENT 

Photochemical rearrangement reaction of 1,4-dienes leading to the formation of 

vinylcyclopropanes is widely known as di-p-methane rearrangement. 

198


1 

H 2C 

2 

R 1 

R 3 

3 4 

R2 

(1,4-diene) 

di-p-methane unit 

5 

R 5 

R 4 

hn 

2 

R 3 

1CH2 

R 1 

4 

3 

R 5 

5 

R 2 

R 4 

(vinylcyclopropane) 

rearranged product 

R 1 

2 

1 

3 

5 

R 5 

R 2 

4 

R 3 

R 4 

199 

(bicyclic product) 

side product 

This is the most general photochemical reaction applicable to acyclic, cyclic, bi and 

tricyclic 1,4-dienes. Zimmermann and his collaborations had extensively studied the reaction, 

and that is why, now-a-days, this rearrangement reaction is also called as Zimmermann reaction. 

Mechanism and Discussion 

The reaction is believed to proceed through diradical pathway, though the species is not 

necessarily intermediate, but may be the transition state. 

2 

R 1 

H 2C R 5 

1 

3 

R 2 

4 

5 

R 4 

R 3 

hn 

R 1 

H 2C R 5 

R 2 

(diradical) 

R 4 

R 3 

R 1 

H 2C 

R 5 

R 2 

R 3 

R 4 

R 3 

1CH2 

It has been established that for acyclic and monocyclic systems, the rearrangement 

proceeds through a singlet mechanism (viz. photochemical rearrangement of 3,3-dimethyl- 

1,1,5,5-tetraphenylpenta-1,4-diene to 1,1-dimethyl-2,2-diphenyl-3-(2,2-diphenyl)vinyl cyclopropanes), 

whereas for bicyclic or tricyclic systems the reaction follows triplet mechanism (viz. 

acetone-sensitized photochemical rearrangement of barrelene to semibulvalene). 

The singlet state reaction is supposed to be concerted and to involve inversion of 

configuration only at C-3; configurations at C-1 and C-5 remain intact. For example, cis-1,1diphenyl-3,3-dimethyl-1,4-hexadiene 

(1) rearranges to (2), in which the side chain is cis, but 

trans-1,1-diphenyl-3,3-dimethyl-1,4-hexadiene (3) rearranges to (4), in which the side chain is 

trans. Similarly, (5) and (6) yield predominantly (7) and (8) respectively. 

2 

R 1 

4 

3 

R 5 

5 

R 2 

R 4


2 

2 

1 

1 

3 4 

hn 

2 

4 

3 

5 

Ph 

1 

5 

Ph 

5 

Ph Ph 

1 Ph 

Ph Ph 

(1) (2) (3) (4) 

3 4 

hn 

2 

4 

3 

5 

2 

1 

3 4 

Ph 

5 

1 Ph 

5 

Ph 

1 

(5) (6) (7) (8) 

CRITICAL VIEWS 

2 

1 

3 4 

(a) The direction of rearrangement is controlled by the ease of electron availability for pbond 

formation in the diradical formed; conversely, is directed by the extent of electron 

delocalization in the diradical formed during the reaction that may be exemplified by the 

following transformation (Scheme I). The substrate (9) gives exclusively (11), not the 

(12). This can be rationalized from the fact that the benzylic radical of (10) can be 

stabilized by delocalization into the aromatic rings and is not readily available for p-bond 

formation as required by route ‘b’; route ‘a’ is therefore followed leading to the formation 

of (11) as a sole product. 

Me 

Me 

hn 

Me 

Me 

Me 

Me Me Ph 

MePh 

Ph 

Ph 

(diradical) 

(9) (10) 

route 'a' 

Me 

Me Me Ph 

Me 

Ph 

route 'b' 

Me 

Me Me 

Me 

Me Ph 

hn 

hn 

Ph 

Me 

Me 

Me 

Me 

(11) 

Ph 

(sol product) 

2 

2 

Me 

4 

4 

3 

3 

5 

5 

Me 

(12) 

Ph 

(not formed) 

Me 

Ph 

200 

Ph 

Ph 

Ph


(b) The reaction has been extended to allylic benzenes, b,g-unsaturated imines and to triplebond 

systems. Asymmetrically sensitized di-p-methane rearrangements has also been 

observed, which leads to the synthesis of optically active products. 

(c) It has been observed that b,g-unsaturated ketones undergo photochemical reaction similar 

to di-p-methane rearrangement involving 1,2-acyl migration and formation of a threemembered 

ring; this particular reaction is known as oxa-di-p-methane rearrangement. 

Here the carbonyl group acts as one of the p-component. 

APPLICATIONS 

i) 

ii) 

Me 

Me 

R 1 

Ph 

O 

O 

R 2 

Ph 

hn 

R 6 

Ph 

R 3 

H 

R 5 

Ph 

hn 

R 4 

hn 

hn 

R 1 

Ph 

O 

O 

Me 

Me 

R 4 

R 2 

Ph 

R 6 

Ph 

R 3 

R 5 

H 

Ph 

201


iii) 

iv) 

2 

O 

3 

7 

1 

8 

4 

(barralene) 

6 

5 

hn 

acetonesensitized 


(proceeds through 

triplet-state mechanism) 


Pointed out 

hn 

t-BuOH 

(direct) 

5 

O 

(~50%) 

3 4 

6 

1 

(semibulvalene) 

7 

Ø Electrocyclic reactions 

Ø Generalized Woodward-Hoffmann rule 

Ø Cycloaddition reactions: correlation diagram and frontier molecular orbital method 

Ø Stereochemical modes of cycloaddition: suprafacial and antarafacial processes 

Ø Orbital symmetry in cycloaddition reaction: correlation diagrams 

Ø Frontier molecular orbital (FMO) method 

Ø Cycloadditions 

Ø 1,3-dipolar cycloadditions 

Ø Cheletropic reactions 

Ø Sigmatropic rearrangements 

Ø The Cope rearrangement 

Ø The Claisen rearrangement 

Ø The Di-pi-methane rearrangement 


1. How does a diene enter cyclo addition? Explain. 

2. Which diene and dienophile one would employ to synthesize Norbornadiene? 

2 

8 

202


3. The butadienes A and B are easily interconverted under thermal conditions. Suggest a 

mechanism. 

Ph 

CD 3 

Ph 

Ph 

Me 

D 

Me 

(A) (B) 

CD 3 

4. Explain the following. 

(a) Ring opening and ring closure of butadiene 

(b) Opening of a 1,3-cyclohexadiene and it’s ring closure. 

5. Illustrate cheleotropic reaction with a suitable example. 

6. Why concerted 1, 3 sigmatropic shift of hydrogen is thermally forbidden? 


1. Explain Frontier Molecular Approach for cycloaddition reaction with suitable examples. 

2. Explain Woodward Hoffmann rule for electrocyclic reactions. 

3. Write the stereo structure of the compound obtained by the Diels Alder reaction of 

dimethyl maleate with butadiene. 

4. Explain di-pi methane rearrangement. 

5. The transition state of the Diels Alder reaction is aromatic and compares with Cope 

rearrangement. Explain. 

6. How is Claisen rearrangement related to Cope rearrangement? Give examples for both. 




2. D. Nasipuri, Stereochemistry of Organic compounds, second edition, New age 

international (P) limited, Publisher, New Delhi. 

Ph 

203


UNIT-VIII 

LESSON: 18 – STEREOISOMERISM: OPTICAL ACTIVITY AND 

CHIRALITY 

CONTENTS 



18.1.1. OPTICAL ACTIVITY 

18.1.2. SPECIFIC ROTATION 

18.1.3. ENANTIOMERS 

18. 2. OPTICAL ACTIVITY AND CHIRALITY 

18.2.1. ASYMMETRIC CARBON (Chiral carbon atom or Stereogenic centre) 

18.3. PROJECTION FORMULAE 

18.3.1. WEDGE PROJECTION 

18.3.2. FISCHER PROJECTION 

18.3.3. SAWHORSE REPRESENTATION 






The aim is to motivate and enable the student to comprehensive knowledge on optical 

activity and Chirality of organic compounds. 


* learnt the optical activity and Chirality of organic compounds. 


Stereochemistry is the branch of chemistry that deals with the study of the special structure 

of molecules and of influence of their structure on physical and chemical properties of 

compounds. In other words, stereochemistry deals with the study of physical and chemical 

properties of stereoisomers. 

204


Isomerism 

Structural isomerism Stereoisomerism 

Optical isomerism 

Enantiomerism Diastereomerism 

Geometrical isomerism 

Isomers are different compounds with different properties that have the same molecular 

formula. This phenomenon is known as isomerism. Isomers that differ in the order in which 

their atoms are bonded are known as structural isomers or constitutional isomers. The order of 

atomic connections that defines a molecule is termed its constitution and two compounds are said 

to be constitutionally isomeric if they have same molecular formula but differ in the order in 

which their atoms are connected. Stereoisomerism is exhibited by isomers having the same 

structure but different configurations. That is, stereoisomers have the same constitution but 

differ only in the spatial orientation of their atoms. 

Optical isomerism is characterized by the compounds having the same structure but 

different configurations and because of their molecular asymmetry (Chirality) they are optically 

active. 

Geometrical isomerism or cis-trans-isomerism is characterized by compounds having the 

same structure but different configurations and because of their non-chiral (non-dissymmetric) 

nature they are not optically active, unless they happen to carry groups that contain asymmetric 

carbon atoms. This type of isomerism is exhibited by compounds that contain double bonds and 

certain ring compounds in which at least two ring atoms contain unequal substituents. 

Geometrical isomerism is a special case of diastereoisomerism. 

18.1.1. OPTICAL ACTIVITY 

Any discussion on stereochemistry starts with the phenomenon of optical activity. The 

ability of a substance to rotate the plane of polarized light is known as optical activity. If a 

substance rotates the plane of polarized light, it is called optically active. On the other hand if a 

substance does not rotate the plane of polarized light, it is said to be optically inactive. Optical 

activity is detected and measured by an instrument called polarimeter. If a substance rotates the 

plane of polarized light in clockwise direction (right), it is called dextrorotatory and is 

designated as (+)-isomer. If the substance rotates the plane of polarized light in anticlockwise 

direction (left), it is known as laevorotatory and is designated as (-)-isomer. 

205


18.1.2. SPECIFIC ROTATION 

The magnitude of optical rotation is directly proportional to the nature of the substance, 

its concentration, cell length, wavelength of light used and temperature. For a given substance 

under a given set of conditions, the magnitude of optical rotation (q) can be expressed as: 

Optical rotation (q) µ cell length (l) ´ concentration (c). 

i.e., q µ l (dm) ´ c (g/ml) 

\q = [a] ´ l (dm) ´ c (g/ml), where [a] is called specific rotation. 

[ ] t 

a = D 

Specific rotation = 

q 

l (dm) ´ c (g/ml) 

18.1.3. ENANTIOMERS 

Observed rotation(degrees) 

Cell length (dm) ´ Concentration 

(g/ml) 

The optical activity was discovered by the French Physicist Jean Baptiste Biot in 1815 at 

the College de France. In 1848, Louis Pasteur made an interesting observation that optically 

inactive sodium ammonium tartrate existed as a mixture of two different kinds of crystals which 

were mirror images of each other. With the help of a hand lens and a pair of tweezers, he 

carefully and laboriously separated them into right and left handed crystals. Although, the 

original mixture was optically inactive, each set of crystals when dissolved in water was found to 

be optically active. Further more, the specific rotations of two solutions were exactly equal in 

magnitude but opposite in sign. The two sets of solutions were exactly equal in magnitude but 

opposite in sign. The two sets of crystals are indeed enantiomers. Enantiomers are optical 

isomers which are related as non-superimposable object and its mirror image. 

18. 2. OPTICAL ACTIVITY AND CHIRALITY 

It is found that if a pure compound is optically active, the molecule is nonsuperimposable 

on its mirror image. The property of non-superimposability of a molecule on 

its mirror image is known as Chirality. If a molecule is not superimposable on its mirror 

image, it is chiral. If it is superimposable on its mirror image then it is achiral. Thus 

Chirality is a necessary and sufficient condition for optical activity. Thus if a molecule is 

chiral, it is non-superimposable on its mirror image and exhibits optical activity. On the other 

hand, if the molecule is achiral, it is superimposable on its mirror image and is optically inactive. 

18.2.1. ASYMMETRIC CARBON (Chiral carbon atom or Stereogenic centre) 

When a molecule contains just one asymmetric carbon atom, it is always chiral and 

hence optically active. Asymmetric carbon atom also called chiral carbon (or stereogenic 

carbon atom) is defined as a carbon atom attached to four different groups, no matter how slight 

the differences among the four groups. For example, optical activity is present in the following 

compound and optical activity has been detected even in such cases as 1-butanol-1-d, where one 

group is hydrogen and another is deuterium. 

206


H 

CH3-CH2-CH2-C-OH D 

Molecules that contain just one asymmetric carbon atom always exist as a pair of 

isomers, which are related as non-superimposable object and its mirror image, called 

enantiomers or enantiomorphs. 

HOOC 

H 3C 

C 

OH 

H 

- 

- 

HO 

Enantiomers of lactic acid 

C 

COOH 

H CH 3 

Enantiomers have identical physical and chemical properties except in two important 

respects. 

(a) They rotate the plane of polarized light in opposite direction though in equal amounts. 

That is, they exhibit same magnitude of optical rotation but in opposite direction. The isomer 

which rotates the plane of polarized light to the right (clockwise) is called dextro isomer and 

designated as (+)-isomer, while the one that rotates the plane of polarized light to the left 

(anticlockwise) is called leavo isomer and is designated as (-)-isomer. 

(b) They react at different rates with other chiral compounds. Enantiomers react at the 

same rate with achiral compounds. 

In general enantiomers have identical properties in a symmetric environment but in an 

asymmetric environment their properties may differ. They react at different rates with achiral 

molecules in the presence of an optically active catalyst. They have different solubilities in an 

optically active solvent; they may have different indeces of refraction or absorption spectra when 

examined in circularly polarized light. 

Although pure chiral molecules are always optically active, a mixture consisting of 

equimolar amounts of enantiomers [ (+) and (-) forms] is always optically inactive, since their 

rotations cancel each other. Such a mixture is called racemic mixture or racemic modification. 

The properties of racemic modification are not always the same as those of individual 

enantiomers. Usually the properties of racemic modification tend to be same in gaseous or liquid 

state or in solution, since such mixture is nearly ideal. But the properties involving in solid state, 

such as melting points and solubilities are often different. Thus, racemic tartaric acid [(± )tartaric 

acid] has a melting point of 204-206 0 C and solubility in water at 20 0 C of 206g/litre, while 

for (+) or (-) enantiomers the corresponding figures are 170 0 C and 139 0 . The separation of 

racemic mixture into its optically active components or enantiomers is known as resolution. 

Although, molecules with one asymmetric carbon atom are always optically active, the 

presence of an asymmetric carbon is neither a necessary nor a sufficient condition for optical 

activity, since optical activity is present in molecules with no asymmetric carbon atoms (eg: 

207


biphenyls, allenes, ansa compounds etc.) and some molecules with two or more asymmetric 

carbon atoms are superimposable on their mirror images and hence optically inactive 

(eg. meso-tartaric acid). 

18.3. PROJECTION FORMULAE 

Our media, the paper and the black-board for drawing chemical structures is two 

dimensional. Hence, it is difficult to represent the three dimensional molecules on a two 

dimensional paper in their three dimensional reality. For this reason, a number of two 

dimensional projections have been introduced. One such projection is wedge projection. 

18.3.1. WEDGE PROJECTION 

This projection is convenient to represent molecules with one and two asymmetric carbon 

atoms. This projection is constructed as follows: of the four groups attached to the tetrahedral 

carbon atom, two groups and the central carbon atom are placed in the plane of the paper such 

that, of the two remaining groups one lies above the plane and the other below the plane of the 

paper. The group which is above the plane of the paper is drawn with a bold or thick wedge and 

the one below the plane of the paper is drawn with a dotted wedge. The enantiomers of 

glyceraldehydes are represented below by the wedge projection. It is often convenient to place 

the longest carbon chain in the plane of the paper. 

OHC 

HOH 2C 

C 

OH 

H 

18.3.2. FISCHER PROJECTION 

HO 

Enantiomers of glyceraldehyde 

C 

CHO 

H CH 2OH 

Although the wedge projection is convenient to represent three dimensional molecules 

with one and two asymmetric carbon atoms, wedge projections become increasingly complicated 

with increasing number of carbon atoms. For this reason, Emil Fischer introduced a projection in 

1891 which is still in use. This projection is constructed as follows. The wedge projection or the 

three dimensional model of the molecule, is so rotated that two groups attached to the 

asymmetric carbon atom are above the plane of the paper and the two groups are below the plane 

of the paper. The molecule is then represented by two lines intersecting at right angles to each 

other. The asymmetric carbon atom is at the point of intersection which is usually not shown. 

Then, the groups which are above the plane of the paper are attached to the horizontal line and 

those groups which are below the plane are attached to the vertical line. It is convenient to place 

the longest carbon chain vertically. The construction of Fischer projection is illustrated with 

glyceraldehydes as an example. 

208


OHC 

HOH 2C 

rotate the molecule 

in the direction of 

groups in the plane 

H 

C 

CHO 

OH 

H 

C OH 

CH 2OH 

CHO 

H OH 

CH 2OH 

HO 

C 

CHO 

H CH 2OH 

CHO 

HO C H 

rotate the molecule 

in the direction of 

groups in the plane 

CH 2OH 

CHO 

HO H 

CH 2OH 

In order to standardize the Fischer projection formulae, the following rules must be 

observed. 

1. Projection formulas may be rotated in the plane of the paper by 180 0 with out their 

stereochemical meaning being changed; the two projections given below refer to the same 

molecule. 

209


COOH 

H OH 

CH 3 

rotate in the plane of 

the drawing by 180 ° 

HO 

CH 3 

COOH 

2. Two or any even number of interchanges (or transpositions) of substituents at an 

asymmetric carbon atom, do not alter the stereochemical of the projection formula. 

COOH 

H OH 

CH 3 

COOH 

interchange 

interchange 

HO 

H 

H/OH CH3/COOH CH 3 

H 

CH 3 

COOH 

3. One such interchange or any other odd number of interchanges of substituents at the 

asymmetric carbon atom will lead to the projection formula of the optical antipode 

(enantiomers) of the original molecule. 

COOH 

H OH 

CH 3 

one interchange 

of H/OH 

Enantiomers 

COOH 

4. It is not permissible to rotate the projection formulas in the plane of the paper by either 

90 0 or 270 0 . 

5. Apart from transpositions, projection formulae can be transformed by rotating a group of 

three substituents either in clockwise or in anticlockwise direction, while keeping the 

fourth substituent stationary. Such a transformation is equivalent to two interchanges of 

substituents and does not alter the stereochemical meaning of the projection formula. 

HO 

CH 3 

HO 

H 

210 

H


COOH 

H OH 

CH 3 

COOH 

H OH 

CH 3 

H 3C 

COOH 

OH 

COOH 

6. Projection formulas may not be lifted out of the paper that is, one must not for example, 

view them from opposite side of the paper; the stereochemical meaning of the formula 

will be changed. 

Although widely used, Fischer projection has certain disadvantages. For compounds 

containing two or more asymmetric carbon atoms, Fischer projection represents the molecule as 

its high energy eclipsed conformation, whereas the staggered conformation is more stable. For 

example, the projection for (-)-threose implies an eclipsing relationship of groups attached to the 

two chiral centres. 

In order to overcome the shortcomings of Fischer projection, two more projections have 

been introduced. 

18.3.3. SAWHORSE REPRESENTATION 

In sawhorse representation, the bond between the chiral carbon atoms is drawn 

diagonally, implying that it runs downwards through the plane of the paper and is slightly 

elongated for clarity. The substituents on each of the carbon atoms and is slightly elongated for 

clarity. The substituents on each of the carbon atoms are then projected on the plane of the paper 

and can be represented in staggered or eclipsed conformations. Eclipsed and staggered 

conformations of (-)-erythrose are shown below. 

H 

H 

CHO 

CH2OH eclipsed 

OH 

OH 

180 ° 

HO 

HOH 2C 

HO 

H 

H 

H 

H 

CH 3 

staggered 

OH 

CHO 

211


In Newmann projection (introduced of Melvin S.Newman of Ohio State University), the 

molecules is viewed along the bond joining the chiral carbon atoms, and these are represented as 

superimposed circles, any one circle being drawn. 

OH 

H OH 

H 

CHO 

CH 2OH 

eclipsed 

HO 

CH2OH H OH 

H 

CHO 

staggered 

The remaining bonds and the substituents are then projected on to the plane of the paper. 

The bonds to the nearer carbon atom are drawn from the centre of the circle and those to the 

further carbon atom are attached to the perimeter. 



Pointed out 

Ø Optical activity 

Ø Specific rotation 

Ø Enantiomers 

Ø Optical activity and chirality 

Ø Asymmetric carbon (chiral carbon atom or stereogenic centre) 

Ø 18.3. Projection formulae 

Ø Wedge projection 

Ø Fischer projection 


1. How will you tell whether a molecule is chiral or not? 

2. State the condition for optical inactivity of conformationally mobile molecule. 


1. Translate the following Fischer projections into staggered forms of Sawhorse and 

Newmann projections. 

(a) 

CH 3 

H Cl 

H OH 

CH 3 

(b) 

COOH 

H OH 

H OH 

COOH 

(c) 

CHO 

H OH 

HO H 

CH 2OH 

212


2. Secondary and tertiary amines with different alkyl groups are expected to be chiral. 

However such molecules have never been resolved. Explain. 

3. Sketch the Sawhorse and Newmann projections of erythro- and threo- forms of 1-bromo- 

1,2-diphenylpropane both in eclipsed and staggered conformations. 


1. P. Ramesh, Basic principles of Organic Stereochemistry, first edition, 2005. 

2. I.L. Finar, Organic Chemistry, Vol. 2., 5 th edition, ELBS & Longman group Ltd., 1974. 

3. Jerry March, Advanced organic chemistry, 4 th edition, John Wiley & sons, New York, 

1992. 

4. D. Nasipuri, Stereochemistry of Organic compounds, Wiley Eastern limited, New Delhi, 

1991. 

213


LESSON: 19 – STEREOISOMERISM: CONFIGURATIONAL 

NOMENCLATURE 

CONTENTS 



19.2 FISHER’S D AND L NOMENCLATURE 

19.3. R AND S NOMENCLATURE 

19.4. R* AND S* NOMENCLATURE 

19.5. CIP NOMENCLATURE OF RACEMATES 

19.6. NOMENCLATURE OF POLYSUBSTITUTED CYCLANES 

19.7. E AND Z NOMENCLATURE 





The aim is to motivate and enable the student to comprehensive knowledge on 

configurational nomenclature of organic compounds. 


* learnt the configurational nomenclature of organic compounds. 


The different modes of representation of three-dimensional chiral molecules on twodimensional 

paper, have already been discussed which include Fischer projection formula, 

sawhorse and Newman projection formulae. These formulae show the spatial structures of the 

molecules in their relative and absolute configuration which might be or might not be known but 

no nomenclatures were given to the formulae. For example, lactic acid has been represented by 

two Fischer projection formulae, one for dextrorotatory and the other for the levorotatory 

enantiomers.The problem now resolves itself into two: (i)Appropriate configurational 

‘descriptors’ have to be given to the structures in the way one say’s ‘right’ and ’ left’ to 

distinguish one’s two hands (ii) Next, one must know which structure belongs to which 

enantiomers (assignment of configuration).It is necessary first to settle on some system of 

configurational nomenclature so that each structure may be identified by a specific name. 

19.2 FISHER’S D AND L NOMENCLATURE 

As early as 1890, Fisher while working in the sugar and amino acid chemistry felt the 

need for establishing relationship among members of a family of compounds (e.g., 

carbohydrates). He established the relative configuration of (+)-glucose and arbitrarily 

represented it by the structure (xvi, Figure 4.5) (he could have very well chosen its mirror 

image)*. He called it D-(+)-glucose, the descriptor ‘D’ referring to the configuration implied in 

214


the formula (I). Any sugar which could be genetically related to (+)-glucose through chemical 

transformations such as (+)-mannose and (-)-fructose was placed in the D family irrespective of 

their sign of rotation (Fisher originally used lower case d and l). the enantiomers were put in the 

L family. Since D-glucose (I) can be degraded into or synthesized from (+)-glyceraldehyde, the 

latter was arbitrarily given the D-configuration represented by II and (-)- glyceraldehydes the Lconfiguration 

represented by III (they retain the C-5 chiral centre of D and L-glucose 

respectively). Most of the sugars (and analogous compounds) may, in principle, be genetically 

related either to D- or to L-glyceraldehyde and their configurations were accordingly defined by 

D or L. This genetic nomenclature, however, did not work since in many cases, both the 

enantiomers of a compound may be chemically correlated to the same glyceraldehydes, e.g., (+)- 

and (-)- lactic acid to D-glyceraldehyde; the former is obtained by reduction of CHO to Me and 

oxidation of CH2OH to CO2H and the latter by oxidation of CHO to CO2H and reduction of 

CH2OH to CH3. 

H 

HO 

H 

H 

H 2N 

CHO 

C 

C 

C 

C 5 

OH 

H 

OH 

OH 

CH 2OH 

(I) 

COOH 

C 

H 

CH 2OH 

H 

H 2N 

HO 

H 

H 

CHO 

C 

OH 

CH 2OH 

(II) 

COOH 

C 2 

C 

C 

C 5 

H 

H 

OH 

CH 2OH 

(V) (VI) 

OH 

HO 

CHO 

C 

H 

CH 2OH 

(III) 

HO 2C 

To circumvent the difficulty, Rosanoff (1906) modified the system and suggested a 

projection nomenclature according to the following conventions: 

(i) As in Fischer’s system, the molecule is written with the longest carbon chain placed 

vertically. 

CH 3 

CH 2 

C 

(IV) 

Ph 

215 

H


(ii) The most highly oxidized end of the chain is placed at the top (as CHO in glucose), 

again following Fischer’s convention. 

(iii) If in the projected structure, the OH group (or any negative group,X) at the bottommost 

(highest-numbered) chiral centre (C-5 in glucose) is on the right hand side, the molecule is 

given D configuration and if it is on the left, the molecule is given L configuration (as in D- and 

L-glyceraldehyde respectively). The Fischer- Rosanoff system does not refer to the origin of the 

compound (non-generic) and is commonly used in all textbooks. 

However, only molecules which can be projected in a manner similar to sugars can fit 

into this scheme of nomenclature. For example, 1-phenylbutyric acid (IV) cannot be written in 

Fischer projection following both the specifications (i) and (ii) simultaneously : either the longest 

carbon chain can be placed vertically as in IV or the highest oxidized end, carboxylic group be 

placed at the top. 

For amino acids, L-(-)-serine with the configuration (V) is used as reference which 

introduces a further complication in defining the configuration of molecule containing both 

hydroxyl and amino groups. Thus 2-amino-2-deoxymannonic acid (VI) may be given D label 

with reference to glyceraldehyde (see C-5) but L label with reference to serine (see C-2). The 

problem can be solved by using subscripts ‘g’ for glyceraldehyde and ‘s’ for serine so that the 

amino- mannonic acid may be designated either as Dg or as Ls (Slocum, Sugarman, and Tucker 

1971). 

19.3. R AND S NOMENCLATURE 

A self-consistent and unambiguous system of configurational nomenclature based on the 

three-dimensional structures of molecules was first introduced by Cahn and Ingold (1951) and 

subsequently elaborated by Cahn, Ingold, and Prelog (1955,1966).The system is known as CIP 

nomenclature after the names of the authors. According to this system, the configuration of a 

molecule is specified uniquely either as R (from rectus, Latin for right) or as S (from sinister, 

Latin for left) which is independent of nomenclature and numbering. Like D and L,R and S are 

also topographical descriptors, used as prefixes* and have nothing to do with the signs of 

rotation. 

Assignment of configuration is done by the application of two rules: the sequence rule 

(consisting of several standard subrules) and the Chirality rule. The sequence rule arranges the 

four ligands of a chiral centre (Cabcd) in a priority sequence, e.g., a>b>c>d (‘a’ having the 

highest priority and‘d’ the lowest), or the ligands may be numbered : 1>2>3>4. The chiral centre 

is then viewed from the side remote from the lowest ranking group (‘d’ or 4) (Figure 19.3.1). If 

from this point of view, the arrangement a ® b ® c (or1 ® 2 ® 3 ) appears in the clockwise 

(right-handed) direction, the configuration is R and if the arrangement appears in the 

anticlockwise (left-handed) direction, the configuration is S. This is known as the Chirality rule. 

216


a 

c b 

R 

a 

C 

c b 

d 

d 

d 

C 

b 

a 

a 

c 

b c 

R S 

Fig. 19.3.1 Chirality rule: R and S nomenclature 

The standard subrules which determine the priority order are six in number (actually, they 

themselves may be called the sequence rules) and have been stated under the headings (0)-(5) 

(Cahn, Ingold, and Prelog 1966)*.They must be applied in succession, i.e., one after the other in 

the order stated. 

Sequence rules or standard subrules 

(0) Nearer end of an axis or a plane precedes the farther end (proximity rule). 

(1) Higher atomic number precedes lower, e.g., S>F>O>N>C>H. 

(2) Higher atomic mass number precedes lower, e.g., T>D>H. 

(3) Cis precedes trans; and Z precedes E. 

(4) Like pair R,R or S,S precedes unlike pair R,S or S,R; M,M or P,P precedes M,P or 

P,M; R,M or S,P precedes R,P or S,M M,R or P,S precedes M,S or P,R; and r 

precedes s. 

(5) R precedes S; and M precedes P. 

For the majority of compounds, only subrules (1) and (2) are important; the other subrules 

apply only to special cases. Subrule (0) is applicable to axial and planar Chirality. Subrule (1) 

needs further elaboration which is done in the following paragraphs: 

1. Atoms directly attached to the central chiral atom must be sequenced first according to 

subrule (1). If the priority still remains undecided for some of the ligands, one passes over to the 

Next atom in the ligands and the exploration continues until a decision is reached on the basis of 

subrules. The following examples illustrate the point: 

-CH2CH3 > -CH2H;-CH2OH > -CH2NH2; -CH2CHF Br > - CH2CHFCl 

(Decision is reached at the italicized atoms) 

It may be noted that subrule (2) must not be used until subrule (1) is completely exhausted; thus 

d 

S 

217


-CH2CH2CH3 > - CD2CH3 because propyl > ethyl (subrule 1); but -CH2CD2CH3 > -CH2CH2 CH3 

(subrule 2). 

2. In case a ligand bifurcates, one must proceed along the branch providing the highest 

precedence until a difference is encountered. The decision must be made at the earliest 

opportunity and once made, cannot be changed from consideration of substituents farther along 

the chain. These points are illustrated below: 

-CH 2CHCH 2Cl 

CH 3 

> -CH2CHCH 2CH3 ; 

CH 3 

CH 3 

-CH 2CCH 3 

CH 3 

CH 3 

> -CH 2CCH 2OH 

3. When the central atom is a part of ring system, each branch is followed until a decision is 

reached as shown in Figure 19.3.2a below (see Prelog and Helmchen 1982 for complicated 

cases): 

a. 

4 

H 

HO 

1 

C 

H 2 

2 

C 

3 C 

H 2 

CH 3 

CH 

CH 

H 

CH 2 

b. 

-CH O 

-CH O.. 

(O)... (C)... 

(A) 

CH 

(B) 

H 

OH 

OH 

-CH O 

Fig. 19.3.2. (a) Priority sequence in ring system; (b) aldehyde versus hydrated aldehyde versus 

hemiacetal. 

4. In the case of atoms with multiple linkages, the atom to which they are multiply bonded must 

be duplicated or triplicated as the case may be at both ends of the multiple bond. The duplicate 

atoms are put into parenthesis and except for hydrogen are made up (complemented) to ligancy 

four with phantom atoms of atomic number zero. Thus the representation of the aldehyde group, 

-CHO is shown (Figure 19.3.2b) along with its hydrated form and hemiacetal for comparison. 

From the structures (A),(B), and (C), it is clear that –CHO has preference over the hydrated form 

(B) but the hemiacetal (C) has preference over the aldehyde (A). The last point illustrates the 

utility of the phantom atom which has lower priority than hydrogen. In the following 

illustrations, (Figure 19.3.3) the phantom atoms are omitted. 

OH 

(C) 

218 

CH 3


C 

OH 

-C 

O 

HC - CH 2 

OH 

C 

(O) 

H 

C 

(C) 

-C CH C 

-C N C 

H H 

C 

C 

H 

C 

C 

H 

C 

(C) 

(C) 

(N) 

(N) 

(C) 

H C 

(C) 

O 

(C) 

H 

C 

(C) 

(C) 

C 

(C) 

(C) 

N 

(C) 

H (C) H 

C 

C 

C 

C 

(C) H (C) 

Fig. 19.3.3 Priority sequence of some common groups 

C 

H CH 

H 

C 

H 

H 

(C) 

CH 3 

OH 

OH 

OH 

CH 3 

CH 3 

C CH 3 

CH 3 

H2 

C N 

H 2C 

CH 

H 2C 

CH 3 

CH 3 

or 

CH 3 

CH 2 

CH 2 

219 

CH 2 

C CH 3 

CH 3


In Table 19.3.1, a few atoms and groups are listed in order of increasing priority. In the 

absence of a lone pair of electrons (in the case of tricoordinate atoms), H has the lowest priority. 

Actually, a lone pair (as on N) is equated to a phantom atom of atomic number zero. 

Table 19.3.1 Atoms and groups with increasing priority 

1. H 

2. D 

3. CH3 

4. CH2CH3 

5. CH2(CH2)nCH3 

6. CH2-CH=CH2 

7. CH2-C º CH 

8. CH2C6H5 

9.CH(CH3)2 

10. CH=CH2 

11. C(CH3)3 

12. C º CH 

13. C6H5 

14. CH2OH 

15. CH=O 

16. COR 

17. CONH2 

18. CO2H 

19. CO2R 

20. NH2 

21. NHCH3 

22. N(CH3)2 

23. NO 

24. NO2 

25. OH 

26. OCH3 

27. OC6H5 

28. OCOR 

29. F 

30. SH 

31. SR 

32. SOR 

33. SO2R 

34. Cl 

35. Br 

36. I 

Once the priority order of the ligands is settled, the configurational assignment is made by 

applying the Chirality rule. If one deals with a three-dimensional model, the task is very simple 

one only has to look at the molecule from the side opposite to‘d’ and determine the order of 

a ® b ® c . Difficulty arises since most of the molecules are represented by Fischer projection. 

The method recommended earlier by Eliel (1962) was to draw the projection always with ‘d’ at 

the bottom as shown in Figure 19.3.1 (bottom row) and then describe a semicircle joining 

a ® b ® c the direction of which indicates the configuration. Any Fischer projection can be 

manipulated either by exchanging two pairs of ligands or rotating a group of three either 

clockwise or anticlockwise to conform to this requirement. This is demonstrated in assigning the 

configurational descriptors to D-(=)-glyceraldehyde and L-(-)-serine respectively (Figure 19.3.4). 

In both the instances, R and S correspond to D and L respectively but this does not mean that the 

two pairs of descriptors are necessarily synonymous (e.g., L-cysteine º R-cysteine)* 

H 

CHO 

C 

OH 

CH 2OH 

D 

(I) 

HO 

(1) 

CHO 

(2) 

C 

H 

R 

(4) 

CH2OH (3) 

Fig. 19.3.4. Assignment of R and S descriptors 

H 2N 

COOH 

C 

H 

CH 2OH 

L 

(II) 

HOH 2C (3) 

220 

COOH 

(2) 

C 

H (4) 

A number of alternative procedures for assigning R and S on the basis of Fischer 

projection have been suggested from time to time. The simplest and most widely accepted one is 

due to Epling (1982). The procedure, named as “very good” (a mnemonic device for “vertical = 

good”) consists of two operations : fixing up the priority order of the ligands and tracing a 

semicircle joining a ® b ® c ignoring ‘d’, the lowest priority group. If ‘d’ is on the vertical 

line in Fischer projection (it does not matter whether it is at the top or at the bottom), the 

sequence gives the correct descriptor* ; if on the other hand, ‘d’ is on the horizontal line, the 

sequence gives the wrong answer and the descriptor assigned on this basis should be reversed. 

The procedure is illustrated with (+) –tartaric acid (I), D-(-)-arabinose (II), and 3-bromobutan-2- 

S 

NH 2 

(1)


ol (III) (Figure 19.3.5). In the descriptors arrived at from the sequence a ® b ® c have to be 

reversed. In the third case, H is on the vertical line in both the chiral cerntres and the sequence 

a ® b ® c gives the correct descriptor. 

H 

HO 

COOH 

C 

2 

C 

3 

(I) 

OH 

H 

COOH 

2(R), 3(R) 

HO 

Fig. 19.3.5. Example of the ‘very good’ mnemonic 

H 

H 

C 2 

(II) 

CHO 

C 3 

C 4 

H 

OH 

OH 

CH 2OH 

2(S), 3(R), 4(R) 

HO 

H 3C 

C 

C 

H 

H 

(III) 

2(S), 3(S) 

Cyclic molecules such as steroids and terpenes are usually projected on the plane of the 

paper and hydrogens (or substituents) located below and above the plane are assigned a and b 

descriptors respectively (a represented by dotted and b by thick lines as shown in 3-cholestanol I 

in Figure 19.3.6) – a system recommended by the Chemical Abstract Service (Pure and Applied 

Chem., 1972,31,283). These descriptors relate to relative configuration and are meaningful if the 

cyclic system is drawn in an accepted way as in steroids and terpenes. For absolute 

configuration, each of the chiral centre in the cyclic molecule must be defined by RS descriptors 

following CIP nomenclature. A convenient method has been suggested by Eliel (1985) which is 

as follows. At any particular chiral centre, one ligand must be clearly in the front (F) or clearly 

in the back (B). This would be regarded as the reference ligand. The order (clockwise or 

anticlockwise) of the remaining three can be very easily determined, all three being in the plane 

of the paper. If this reference ligand is 4/B (lowest locant and in the back), the sequence of the 

remaining three ligands would give the correct descriptor. So 4/B(+) may be used as a 

mnemonic [(+) stands for correct]. For other combinations, the numbers will alternate with 

signs, e.g.,4/B(+),3/B(-),2/B(+),1/B(-) and 4/f(-),3/F(+),2/F(-),1/F(+). For example, the C-10 

chiral centre of cholestanol (XXIV) corresponds to 4/F and so although the order 1 ® 2 ® 3 is 

221 

CH 3 

Br


b 4 

11 

1 Me 1 9 

2 

(b) 

HO 

3 

3 

4 

10 H 

2 

5 

6 

H H 

(a) a 

(XXIV) 

12 

H 

8 

7 

Fig. 19.3.6. 3(S), 5(S), 8R, 9(S), 10(S), 13R, 14(S), 17R, 20(S), -cholestan-3-ol (Numericals in 

circle represent priority order of substituents at C-10). 

clockwise, the configuration is S. The configurational labels at the other chiral centres may be 

worked out likewise. 

An algorithmic rule for assigning R and S descriptors to a chiral centre in cyclic 

molecules has recently been worked out (Kotera 1986). However, the procedure is difficult to 

remember and it may be of academic interest only. 

19.4. R* AND S* NOMENCLATURE 

The R, S nomenclature when applied to a molecule with multiple chiral centres, fixes 

both the relative and the absolute configuration. Thus 1R-bromo-3S-chloro-5R-flurocyclohexane 

refers only to the enantiomers (I) (Figure 19.4.1). It often happens that pure enantiomers are 

available with known relative but unknown absolute configuration. In such cases, the R, S 

system of nomenclature is modified as follows (IUPAC Commission 1976). The atoms are 

numbered such that the chiral centre having the highest priority ligand, e.g., C-Br in I is given the 

lowest number (lowest lovant). The molecule is so written that the lowest chiral lovant gets the 

R configuration. Assignment to the other chiral centres is made by the usual method and 

H 

H 

Br 

H 

Me 

H 

13 

14 

H 

20 

17 

F Cl 

H 

16 

15 

Br 

(I) (II) 

or 

H 

F Cl 

H 

222


Fig. 19.4.1. R* and S* nomenclature: 1(R*)-bromo-3(S*)-chloro-5(R*)-fluorocyclohexene 

each of the descriptors is put under asterisk (pronounced as R-star and S-star) to indicate that 

they represent relative configuration. Thus 1R*-bromo-3S*-chloro-5R*-fluorocyclohexane 

represents either of the enantiomeric structures (I) and (II). 

19.5. CIP NOMENCLATURE OF RACEMATES 

For the configurational assignment to racemates, IUPAC Commission recommends the 

joint use of R,S for labeling, a chiral centre, Thus (± )-tartaric acid is designated 2RS,3RSdihydroxysuccinic 

acid. 

19.6. NOMENCLATURE OF POLYSUBSTITUTED CYCLANES 

Polysubstituted cyclanes, e.g., cyclopentanes, cyclohexanes etc. exit in a number of 

stereoisomers (diastereomers and enantiomers) depending on the number and nature of the 

substituents. The disubstituted cyclanes give two diastereomers which can be conveniently and 

unambiguously described as cis and trans isomers, e.g., cis-and trans-2-methylcyclohexanols (I) 

and (II) (Figure 19.6.1). Each of the diastereomers in turn gives two enantiomers which can be 

named, following the R,S nomenclature, as R,S and S,R for the cis and S,S and R,R for the trans 

isomer (use 4/B rule) as shown in the Figure. 

Me OH 

OH Me 

Me H 

H Me 

2 H H 

1 1 

H 

2 

H 

2 

H 

1 

OH 

1 

OH H 

2 

1R, 2S 1S, 2R 1S, 2S 1R, 2R 

(I), cis (II), trans 

Fig. 19.6.1. Disubstituted cyclohexanes 

Difficulty arises when the number of substituents increases, e.g., dimethylcyclohexanols 

(I)-(IV) (Figure 19.6.2). The prefixes, cis and trans are no longer unambiguous and, if applied 

without any reference, lead to confusion; thus compound (I) may be called cis with respect to the 

two methyl groups but trans with respect to the 4-methyl and 1-hydroxyl group. Since many of 

these compounds are achiral (meso) (I-IV), the R, S nomenclature also becomes inapplicable. 

Moreover, the steric relationship does not become immediately apparent from such 

Me 

4 1 

Me Me 

5 

OH 

1 

H 

Me 

Me 

5 

H 

1 

OH 

Me 

H 

5 

OH 

H 

Me 

H 

OH H 

3 

H 

H 

3 

H 

Me 3 

H 

(I) (II) (III) (IV) 

223


Fig. 19.6.2. Polysubtituted cyclohexanes 

nomenclature. To obviate this difficulty, a method of nomenclature known as Beilstein system 

(see Eliel 1971) has been adopted which is as follows: 

(i) A reference group denoted by symbol ‘r’ is specified with respect to which the other 

substituents are described as cis or trans. 

(ii) The r-group is so chosen that it is attached to the lowest lovant (the lowest numbered 

ring member) according to IUPAC rules (vide supra). 

(iii) If two ligands are attached to the lowest locant, that one is selected as r-group which 

has preference in the IUPAC nomenclature. 

(iv) When there are two constitutionally equivalent pathways of going around the ring 

starting from the lowest lovant, that giving the cis attachment to the second substituent (the first 

being the r-group) is chosen. 

Following the rules, the compounds (I), (II), (III), and (IV) are named respectively as 1, 

trans-4-dimethylcyclohexan-r-1-ol, (4-Me is trans to OH ), cis-3,cis-5-dimethylcyclohexan-r-1ol, 

trans-3,trans-5-dimethylcyclohexan-r-1-ol, and cis-3-trans-5-dimethylcyclohexan-r-1-ol 

[according to rule(iv), the carbon bearing cis methyl is counted as 3]. The common practice is to 

abbreviate the names, by replacing cis and trans by c and t respectively. 

The structure (IV), although chiral, has S-configuration both at C-3 and at C-5 which 

makes it impossible to give a configurational descriptor to C-1. In fact, C-1 is chirotopic (as 

judged by local symmetry) but non-stereogenic (exchange of H and OH does not give any new 

stereoisomer). On the other hand, C-1 in I-IV is achirotopic but stereogenic. 

19.7. E AND Z NOMENCLATURE 

It has been shown that olefinic compounds like 2-butene can exist in two diastereomeric 

forms which are called cis and trans isomers. The necessary and sufficient condition for this type 

of isomerism is that ‘a’ and ‘b’ in Cab = Cab must be non-equivalent. In the case of Cab = Nx, 

(Nx = Nx), the missing substituent is the lone pair of electrons on nitrogen. Since this isomerism 

owes its existence to the presence of a p - bond, it has been called p -diastereomerism (Pierre 

1971) to distinguish it from s -diastereomerism exhibited by cyclic compounds*. The p - 

diastereomers are two-dimensional molecules (if one ignores the geometry of the ‘a’ and ‘b’ 

groups), possess a plane of symmetry, and therefore are achiral. On the other hand, the s - 

diastereomers are three dimensional and may be chiral. For molecules of the type, Cab = Cab or 

Cab = Cac, the terms ‘cis’ and ‘trans’ are adequate and unambiguous. But if three or four of the 

substituents are different, this nomenclature leads to ambiguity and sometimes to total confusion. 

An easy solution to the problem is provided by arranging the pair of ligands at each 

trigonal carbon in CIP sequence. Then if the groups of higher priority are on the same side, the 

configuration is seq-cis; if they are on the opposite sides, the configuration is seq –trans (CIP 

1966). Thus if a precedes b and a’ precedes b’, the configuration of the compounds (I) and (VIII) 

(Figure 19.7.1) are seq-cis and seq-trans respectively. Later, the system has been modified 

(Blackwood et al 7968), the two terms being replaced by two shorter symbols, X (from the 

German zusammen meaning ‘together’) and E (from the German entgegen meaning ‘across’) 

which are used as prefixes to the olefins. According to this system, b - methylcinnamic acid (III) 

is called E-3-phenylbut-2-enoic acid (here Ph and CO2H groups are fiducial*). The previously 

called cis-1,2-dichlorobromoethene (c) is now known as E-1-bromo-1,2-dichloroethene which 

goes to prove that E and Z do not always correspond to trans and cis. 

224


a 

b 

C C 

a' 

b' 

a 

b 

C C 

b' 

a' 

H 3C 

C 6H 5 

C C 

(I) (II) (III) 

Cl 

H 

C C 

Cl 

Br 

H 3C 

C 6H 5 

C N 

OH 

H 3C 

C 6H 5 

(IV) (V) (VI) 

H3C 7 6 

C C 

Ph 

H 

Cl 

5 

C 

(VII) 

H 

3 

C 

4 

C 

H 

H 

2 

C 

COOH 

Fig. 19.7.1. Examples of E and Z nomenclature 

H 3C 

HOOC 

C C 

(VIII) 

COOH 

H 

C N 

C C 

OH 

COOH 

This system leads to a great simplification in the nomenclature of the diastereomeric 

oximes for which the (often ambiguous) terms ‘syn’ and ‘anti’ were previously coined. Thus the 

syn (V) and the anti (VI) oximes of acetophenone are now called Z- and E-isomers respectively. 

In the case of compounds, containing more than one non-cumulated (belonging to 

different carbon atoms) double bonds, the number of p -diastereomers (2 n where n is the number 

of non-equivalent double bonds) increases. The descriptors Z and E can be applied to each 

diastereogenic unit. Thus the triene (VII) is 6-chloro-7-phenylocta-2Z, 4Z, 6E-trienoic 

acid.Cumulenes with an odd number of cumulated (consecutive) double bonds with two = Cab as 

terminal groups display p -diastereomerism and E,Z nomenclature is applicable to them also. 

Thus the cumulene (VIII) is E-isomer. 



Pointed out 

Ø Fisher’s D and L nomenclature 

Ø R and S nomenclature 

CH 3 

225


Ø R* and S* nomenclature 

Ø Cip nomenclature of racemates 

Ø Nomenclature of polysubstituted cyclanes 

Ø E and Z nomenclature 

19.9. POINTS FOR DISCUSSION 

1. Designate the configurations of the products of the following reaction as D/L and R/S. 

Cl 

Cl 

(i) 

(ii) 

H 3C 

H 2CH 3C CH 3 

H 

(D) or (S) 

b 

I 

H 

H 2CH 3C CH 3 

Cl 

H 


I 

COOCH 3 

Cl 2/light 

a 

CN 

H 2CH 3C CH 2Cl 

H 3C 

H 

CN 

H 

COOCH 3 




1992. 


1991. 

226


LESSON: 20 – STEREOISOMERISM: CONFORMATION OF ACYCLIC 

AND CYCLIC COMPOUNDS 

CONTENTS 



20. 2. CONFORMATIONS OF ETHANE 

20. 3. CONFORMATIONS OF 1,2–DIHALOGENOETHANES 

20. 4. CONFORMATIONS OF CYCLOHEXANE 

20. 4. 1. GEOMETRY OF THE CYCLOHEXANE RING SYSTEM 

20. 4. 2. EQUATORIAL AND AXIAL BONDS 

20. 4. 3. RING INVERSION 

20.4.4. FLEXIBLE CONFORMATIONS 

20. 5. CONFORMATIONS OF MONO AND DI-SUBSTITUTED 

CYCLOHEXANES 

20.5.1. MONOSUBSTITUTED CYCLOHEXANE 

20. 5. 2. DISUBSTITUTED CYCLOHEXANES 

20.5.2.1. 1,2–DISUBSTITUTED CYCLOHEXANE 

20.6. DECALINS: Bicyclo [4.4.0] decane 

20.6.1. GEOMETRY 

20.6.2. SYMMETRY 

20.6.3. ENTHALPY AND FREE ENERGY 

20.6.4. EFFECT OF ANGULAR METHYL GROUP 

20.7. CONFORMATIONS OF PERHYDROPHENANTHRENE 

20.8. CONFORMATIONS OF PERHYDROANTHRACENE 






The aim is to motivate and enable the student to comprehensive knowledge on 

conformation of acyclic and cyclic organic compounds. 


* learnt the conformation of acyclic and cyclic organic compounds. 


The total energy possessed by a molecule is directly related to its geometry. A molecule 

will adopt that geometry that minimizes its total energy. Many molecules exhibit strain caused 

by non-ideal geometry and the decreased stability of a molecule is called strain energy. The 

sources of strain in alkanes and cycloalkanes are : 

a) Bond length distortion : It is the destabilization of a molecule that results when one or 

more of its bond distances are different from normal values. 

227


b) Angle strain : It is the destabilization that results from the distortion of bond angles from 

the normal values. 

c) Torsional strain : It is destabilization that results from eclipsing of bonds on 

adjacent atoms. 

d) Van der Waals strain : It is the destabilization that results when atoms or groups on nonadjacent 

atoms approach too close to each other. 

The various momentary spatial arrangements of atoms of a molecule that result from 

rotation about single bonds are known as conformations. That is, a molecule of a given structure 

and configuration can have different conformations. Conformational analysis of physical and 

chemical properties of a compound in relation to its geometry and population of its conformers. 

20. 2. CONFORMATIONS OF ETHANE 

Consider the ethane molecule, CH3-CH3 and imagine that one methyl group is rotated 

about C-C bond as axis with other methyl group at rest. Figure 20.2.1 represents the change in 

Fig. 20.2.1. Potential energy of ethane as a function of angle of torsion (dihedral angle). 

potential energy of thane in the course of one complete rotation about C-C bond. Potential 

energy is plotted on Y-axis and the angle of torsion (or dihedral angle) (q ) is plotted on X–axis. 

In the case of ethane, there are six conformations of interest, the so called eclipsed conformations 

(Ia, Ib and Ic) corresponding to energy maxima for which q = 0°, 120° or 240° and the so called 

staggered conformations (IIa,IIb and IIc) which correspond to energy minima for which q = 60°, 

180° and 300°. These conformations are represented in saw-horse and Newman projections 

(Figure 20.2.1) 

H 

H 

H 

H 

H 

H 

H 

H 

H 

H 

H 

H 

Eclipsed conformations of ethane (q = 0°, 120°, 240° and 360°). 

Ia 

228


H 

H 

H 

H H 

H 

H 

H H 

H 

H 

H 

IIa 

Staggered conformations of ethane (q = 60°, 180° and 300°). 

Figure 20.2.1shows that the staggered conformations (IIa, IIb and IIc) of ethane are 12 

KJ/mol (2.9 Kcal/mol) lower in energy than the eclipsed conformations (Ia,Ib and Ic) and all 

energy minimia (stable conformers) are identical. A number of factors contribute to the stability 

of the staggered conformations. The staggered conformations allow for the maximum separation 

of bonded electron pairs. Electron pair repulsions are greatest when the bonds are eclipsed and 

least when the bonds are staggered. The destabilization associated with the eclipsing of bonds on 

adjacent atoms is called torsional strain. Since three pairs of eclipsed bonds produce 12.0 

KJ/mol (2.9 Kcal/mol) of torsional strain, it is reasonable to assume that each pair of eclipsed 

bonds contribute 4 KJ/mol (1 KJ/mol) for an alkane. The 12 KJ/mol of rotational barrier in 

ethane is quite small and even at room temperature the fraction of collisions with sufficient 

energy is large enough that rapid interconversion between staggered conformations occurs. In 

other words, internal rotation in ethane is not completely free but is in an exceedingly rapid 

process and conformational equilibrium is reached readily. 

20. 3. CONFORMATIONS OF 1,2–DIHALOGENOETHANES 

In gaseous state at 22° C,1,2-dichloro and 1,2-dibromoethane exist predominantly in anti 

conformation (Ia) (73% and 83%) like n-butane (67%). However, the greater stability of anti 

form (Ia) in case of 1, 2–dihalogenoethanes compared with n-butane is due to the combined 

electronic (dipole-dipole) and steric effects. In polar solvents and in liquid state the dipole-dipole 

repulsion decreases due to high dielectric constant of the solvent and the proportion of the 

gauche conformations (Ib & Ic) increases. 

X 

H H 

H 

X 

H 

X 

H X 

H 

H 

H 

X 

X H 

anti (Ia) more stable gauche (Ib) gauche (Ic) 

Fig. 20.3.1. Conformation of 1,2-dihalogenoethanes 

H 

H 

H 

229


As the number of halogen substituents increases as in 1,1,2,2- tetrahalogenoethenes 

(Figure 20.3.2), the gauche conformations (IIIb & IIIc) become forms (IIIb & IIIc) over anti 

(IIIa) is attributed to the widening of X-C-X bond which stablies the gauche over anti. 

H 

Br Br 

Br 

H 

Br 

H 

Br H 

Br 

Br 

Br 

Br 

H 

H Br 

anti (IIIa) gauche (IIIb) gauche (IIIc) 

Fig. 20.3.2. Conformation of polyhalogenoalkanes 

20. 4. CONFORMATIONS OF CYCLOHEXANE 

more stable 

The cyclohexane ring system is by far the most commonly occurring of cycloalkanes in 

natural products doubtless because of its stability and ease of its formation. In 1890, Sachse 

proposed that cyclohexane ring can exist in two non-planar (puckered) forms (chair and boat) 

which are free from bond angle strain. Since Sachse’s theory of strainless rings required the 

existence of two isomeric forms of cyclohexane and all attempts to isolate them failed at that 

time, Sachse’s theory was unrecognized for a long time. In 1918, Mohr revived Sachse’s theory 

and explained the absence of isomeric forms of cyclohexane due to rapid interconversion of two 

forms. Mohr later pointed out that the union of two cyclohexane rings may result in the 

formation of two stereoisomeric forms – the cis and the trans decalins which can no longer be 

interconverted without bond rupture. Later, the two isomeric forms of declaims were realized. 

According to the original assumption, the boat and chair conformations were considered 

to be equally probable for cyclohexane. However, the 1947, Hassel established by means of 

electron diffraction studies that cyclohexane exists predominantly in two chair conformations. 

20. 4. 1. GEOMETRY OF THE CYCLOHEXANE RING SYSTEM 

The chair form of cyclohexane ring system (I) is represented in the Figure 20.4.1.1, with 

the vertical C3 axis. The Newman projections of chair forms of cyclohexane reveal that there are 

six gauche-butane interactions of chair forms of cyclohexane reveal that there are six gauchebutane 

interactions and consequently the enthalpy of cyclohexane chair form is estimated as 

3.3´ 6 = 19.8 KJ/mol. 

H H 

5 

H H 

6 

H 

H H H 

4 3 

H 

H 2 

H 

C 3 

1 

H 

H 

H 

5 

H 

H 

4 

3 

56° 

6 

H 

H 

1 

2 

Br 

H 

H 

Br 

230


H H 

4 

H H 

5 

H 6 H 

H H H 

3 H 2 

1 

H H 

H 

3 

H 

H 

H 

1 

2 H 

H 

4 

H 

6 

H 

H 

5 H 

Fig. 20.4.1.1 

The chair form of cyclohexane belongs to D3 point group. The principal axis is C3 and 

there are three binary axes passing through the three opposite sides three diagonal planes (sv) 

pass through the opposite corners. Its symmetry number (s) is 6. 

20. 4. 2. EQUATORIAL AND AXIAL BONDS 

The twelve C-H bonds in the chair form of cyclohexane (I) are of two types. Six of the 

C-H bonds called axial are parallel to the C3 axis and are represented by vertical lines in the 

plane of the paper. These axial bonds are (three above and three below the plane of the 

molecule) alternately directed up and down on adjacent carbon atoms. The remaining six C-H 

bonds are inclined at an angle of 109 0 28’ to the axis and are described as equatorial bonds. The 

axial hydrogens are homotopic relative to each other, since they can be interchanged by rotation 

around C3 and C2 axes. The same is true of equatorial hydrogens relative to each other. 

However, the axial set of hydrogens is diastereotopic with equatorial set of hydrogen atoms. 

Ha 

Ha 

Ha 

(I) 

Ha 

Ha 

C 3 

20. 4. 3. RING INVERSION 

Ha 

He 

He 

H 

H 

H 

3 

H 

4 

H 

H 

H 

H 

3 

2 

C 3 

2 

5 

1 

4 

He 

H 

H 

H 

H 

1 

6 

He 

He 

The cyclohexane ring is conformationally mobile. Through a process known as ring 

inversion or ring flipping, one chair conformation (Ia) is converted into another chair (Ib). Since 

the activation energy for the cyclohexane ring inversion is only 42KJ/mol, ring inversion occurs 

rapidly at room temperature. In between the chair forms, there are two other notable 

conformations, the skew boat (III) which is less stable than the chair and the boat (II) which is 

30KJ/mol less stable than the chair (Figure 20.4.1). 

He 

H 

6 

H 

H 

5 

H 

231


Fig. 20.4.1. Energy profile and conformations of cyclohexane. 

The most important consequence of ring inversion is that any substituent that is axial in 

the original chair conformation (Ia) becomes equatorial in the ring flipped form (Ib) and viceversa. 

It should be noted that during ring inversion no change in the relative configuration ever 

occurs, that is, a-substituent remains a and b-substituent remains b; likewise, cis-remains cis and 

trans remains trans; (R) remains (R) and (S) remains (S). 

X(b) 

a 

H 

Y 

e 

H 

(Ia) 

Cis 

20.4.4. FLEXIBLE CONFORMATIONS 

The boat (II) and the twist boat (III) constitute two significant conformations of the 

cyclohexane. The conventional boat (II) belongs to C2v point group and is free from bond angle 

strain but suffers from significant torsional strain due to eclipsing of four boat equatorial and 

boat axial hydrogens on C-2, C-3 and C-5, C-6. In addition, the hydrogens at C-1 and C-4 

approach so close to each other that the distance between them (183pm) is less than the sum of 

the van der Waals radii (241 pm) of hydrogen atoms. This leads to a non-bonded interaction 

between C-1 and C-4 hydrogen atoms, often called bowsprit-flagpole interaction. 

II 

X 

H 

Y 

H 

Y 

(Ib) 

a 

H 

232 

Cis 

e 

X


eclipsed hydrogen 

H 

bs 

H 

H 4 

5 6 

be 

3 

be 

fp 

H 

be 

H 

1 

2 be 

ba 

ba 

ba ba 

(II) 

1 

H 

6 

4 

2 

5 H 3 

H 

H H 

eclipsed hydrogen H 

H 

H 

3 

H 

H 

H 

2 

3 

2 

4 

(III) 

Fig. 20.4.4.1. Extreme boat form of cyclohexane showing interfering and eclipsed hydrogens. 

The boat form (II) consists of four gauche-butane interactions (1:2, 3:4, 4:5 and 6:1) and 

two eclipsed butane interactions (2:3 and 5:6) and the total strain may be computed as 

4 ´ 3. 

3 + 2´ 

18 = 49. 

2 KJ/mol. The difference in enthalpy between the chair and boat forms is 

thus 29.4 KJ/mol, the enthalpy of the chair being 19.8 KJ/mol. 

A modified boat conformation known as twist boat (or skew boat) (III) results when the 

boat (II) form is so twisted that the flagpole bowsprit hydrogens move away from each other and 

torsional interactions are also reduced. As a result the conformation becomes more stable. Twist 

boat conformation (III) belongs to D2 point group and hence chiral. Although, the boat and twist 

boat conformations are of high energy they have favorable entropy due to more degrees of 

freedom than chair and the population of flexible form is approximately one in 10,000 at ambient 

temperature. 

20. 5. CONFORMATIONS OF MONO AND DI-SUBSTITUTED CYCLOHEXANES 

20.5.1. MONOSUBSTITUTED CYCLOHEXANE 

5 

1 

6 

1 

4 

H 

H 

6 5 

233 

H 

H


Introduction of a substituent does not significantly affect the rate of conformational 

inversion, but does affect the equilibrium distribution between alternative chair forms. All 

substituents that are axial in one chair conformation become equatorial on ring inversion and 

vice-versa. Monosubstituted cyclohexane (e.g. methylcyclohexane) exists in two non-equivalent 

diastereomeric chair conformations, one with equatorial substituent (IVa) and the other having 

the substituent in axial position (IVb), the former predominates at the equilibrium. For 

0 

methylcyclohexane, D G for the equilibrium is 7.50 KJ/mol, corresponding to a composition of 

95% equatorial methylcyclohexane. 

H 

H 

4 

H 

H 

3 

2 

5 

H 

H 

1 

6 

CH 3 

H 

4 

5 

3 2 

The equatorial preference of the methyl group may be related conceptually to the greater 

stability of the anti conformation of h -butane compared to gauche conformation. The axial 

methyl group of methylcyclohexane forms a part of two gauche-butane fragments (Me-C1-C2-C3 

and Me-C1-C6-C5) while an equatorial methyl group is stereochemically similar to anti butane 

conformation. These are shown in heavy lines in the figure 9. 4 and one of them can be seen 

4 

H 

5 

H 

H 

5 

H 

3 

H 

H 

4 

6 

H 

2 

CH 3 

a 

1 

H 

H 

CH 3 

(IVb) (IVa) 

3 

6 

CH 3 

H 

2 

1 

CH 3 

H 

H 

H 

4 

H 

H 

3 

H 

2 

5 

6 

H 

1 

H 

H 

1 

H 

6 

234 

CH 3 

CH 3 

CH 3 

H


H 

3 

H 

H 

H 

4 

and 

5 

2 

CH 3 

H 

6 

1 

H 

H 

clearly in Newman projection. No such interaction is present in equatorial methylcyclohexane. 

Since the gauche conformer of h -butane is 3.3 KJ/mol higher in energy than the anti conformer, 

interactions is less stable than the equatorial methylcyclohexane (IVa) by 6.6 KJ/mol 

(2´3.3 KJ/mol). The potential energy diagram of methylcyclohexane as a function of 

conformation is given in Figure 20.5.1.1. 

Fig. 20.5.1.1. Potential energy methylcyclohexane as a function of conformation. 

The axial methyl group of methylcyclohexane (IV b) experiences VanderWaals 

repulsion with axial hydrogens at C-3 and C-5. Interactions of this type are called 1,3-diaxial 

interactions and substituents in 1,3-diaxial orientation with respect to each other are said to be 

syn axial. The result of repulsion between axial methyl group and syn axial hydrogen leads to a 

slight flattening of the ring. 

The free energy difference between conformers is referred as conformational free energy 

or sometimes A value. For substituted cyclohexanes, the equilibrium is written as 

axial 

equatorial 

DG 0 = - RT lnK where K = 

4 

3 

[equatorial] 

[axial] 

0 

Since the D G will be negative when equatorial conformation is more stable than the 

0 

0 

axial, the value of - D G is positive for substituents that favour equatorial position. The - DG 

value is larger, the greater the preference for the equatorial position. 

5 

2 

6 

H 

CH 3 

1 

H 

235 

H


0 

Conformational free energy values (- D G ) for many substituents have been determined 

by NMR method at low temperature. At -80° C, the NMR spectrum of cyclohexyl iodide is well 

resolved and clearly indicates the presence of two conformations. In general equatorial 

hydrogens resonate at lower field than the constitutionally similar axial hydrogens. The 

multiplet at higher field (d 3.80) is a triplet of triplet with vicinal coupling constant of 3.5 and 

12Hz. This multiplet is assigned to the axial methane proton of equatorial cyclohexyl iodide, 

since it is coupled to the adjacent axial proton (C-2) by a large trans coupling and to the adjacent 

equatorial proton (C– 2) by a small gauche coupling constant. The multiplet at the lower field 

(d 4.50) appears as a broad peak because the equatorial methane proton of the axial cyclohexyl 

iodide is coupled approximately equally to vicinal equatorial and axial protons by small gauche 

coupling. F the coupling constants were equal, the signal would appear as a quintet. The relative 

0 

area of axial methane proton to equatorial methane proton is 3.4 and corresponds to a - D G 

value of 1.88 KJ/mol. 

equatorial isomer 

H 

Ha 

e 

He 

I 

I 

H 

d 3.80 

axial methine 

Fig. 20.5.1.2. NMR spectrum of cyclohexyl iodide at -80° C 

Ha 

He 

axial isomer 

I 

He 

H 

I 

236 

d 4.50 

A second important method for determining the conformational free energies involves 

establishing an equilibrium between diastereoisomers differing only in the orientation of the 

designated substituent. The equilibrium constant can then be determined and used to calculate the 

free energy difference between the diastereoisomers. For example, cis- and trans-4-tbutylcyclohexanols 

can be equilibrated using a nickel catalyst in refluxing benzene to give a 

mixture containing 28% cis-4-t-butylcyclohexanol (diaxial-OH) and 72% trans-4butylcyclohexanol 

(equatorial-OH) (Figure).


H 

28% 

OH 

cis-4-t-butylcyclohexanol 

H 

nickel 

benzene, 80 ° C 

H 

72% 

H 

OH 

trans-4-t-butylcyclohexanol 

The equilibrium constant for the above reaction leads to a value of 2.9 KJ/mol for - D 

for the hydroxyl substituent. 

Among the halogen substituents, fluorine is the least conformationally demanding and the 

preference for the equatorial orientation is nearly same for chlorine, bromine and iodine. The 

larger van der Waals radii of iodine and bromine relative to chlorine are compensated by the 

greater C-I and C –Br bond lengths, which decrease the repulsion between halogen and syn-axial 

hydrogens. The electrons of C-I and C-Br bonds are also more polarisable and lead to increased 

attractive interaction between halogen and other atoms. 

The alkyl groups’ methyl, ethyl and isopropyl have similar conformational energies with 

isopropyl being slightly larger than methyl and ethyl. The similarity of the conformational 

energies of these three substituents is due to the rotation of the alkyl groups around the bond 

between the substituent and the ring so that the ring adopts a conformation that minimizes the 

effect of additional methyl substituents in ethyl and isopropyl groups. 

H 

H 

H 

R 

H 

R' 

methyl : R = R 1 = H 

ethyl : R = H 1 R 1 = CH 3 

isopropyl : R = R 1 = CH 3 

A tertiary butyl substituent experiences strong van der Waals repulsion with syn axial 

hydrogens and this strain is not relieved by rotation of tertiary butyl substituent about the bond to 

the ring. The conformational free energy of t-butyl group has been estimated as 22.5KJ/mol. 

The strong preference for t-butyl group to occupy the equatorial orientation has made it a highly 

useful group for the study of conformationally biased systems. 

20. 5. 2. DISUBSTITUTED CYCLOHEXANES 

Non-gemninally disubstituted cyclohexanes exist as a set of three positional isomers, 1,2-, 

1,3 and 1,4. Each set can exist as a pair of geometrical isomers, cis and trans, each of which in 

turn can exist in two interconvertible chair conformations. Depending upon symmetry, each 

positional isomer may exhibit enantiomerism. (Each positional isomer has 2 chiral centers, so 

the number of stereoisomers is 4 (2 2 ). They are a cis – pair of enantiomers and trans pair of 

enantiomers. Further the cis and trans isomers exist in two interconvertible chair 

237 

0 

G


conformations). The stereochemical aspects of disubstituted cyclohexanes are illustrated with 

dimethylcyclohexanes. 

20.5.2.1. 1,2–DISUBSTITUTED CYCLOHEXANE 

1. cis-1, 2-Disubstitutedcyclohexane (eg. cis-1,2-dimethylcyclohexane) 

X 

H 

X 

H 

X = Y = Me 

1,2-Substituents of a cyclohexane are said to be cis, if they occupy axial and equatorial 

orientation. Cis-1,2-dimethylcyclohexane exists as two energetically equivalent axialequatorial 

(a,e) (Ia) and equatorial–axial (e,a) (Ib) chair conformations which are not 

superimposable on their mirror images. However, the classical (planar) formula of BcisB-1,2dimethylcyclohexane 

has a plane of symmetry and therefore, represents a meso form. If the 

conformational representations of cis-1, 2-dimethylcyclohexane are examined, each chair form is 

devoid of mirror symmetry and hence expected to be chiral. However, the two conformational 

H 

C 3 

(Ib) 

H 

(Ia) 

CH 3 (a) 

H 

CH 3 (e) 

CH 3 (a) 

H 

enantiomers 

120 ° 

CH 3 (e) 

H 

(e) H 3C 

CH 3 (a) 

H 

238


isomers resulting from ring inversion are also mirror images of each other. This can readily be 

seen by rotating the chair form Ib by 120 0 around the C3-axis. Since the two conformational 

isomers are equienergetic and are present in equal amounts, cis-1, 2 –dimethylcyclohexane exists 

as a racemate ( ± ); since the potential energy barrier between the two conformers is too low to 

allow separation, the racemate is inseparable. Thus, cis-1,2-dimethylcyclohexane is a nonseparable 

racemate. 

Either of the chair conformations contain three gauche-butane interactions (two for one 

axial methyl and one for a-e dimethyl) corresponding to a potential energy difference of 

11.2KJ/mol (with respect to hypothetical structure with no extra interaction). The entropy of 

such compounds originates from three sources (i) entropy due to symmetry number (-RTlns) 

ii) entropy due to mixing of conformers iii) entropy due to (± )-mixture. For cis-1,2dimethylcyclohexane 

(C1 symmetry) s is 1 and so its contribution to the entropy is nil; the 

second and third factors happen to be the same. The two conformers being enantiomeric 

contribute an entropy of mixing, Rln2. 

If the substituents are different and differ in size ( X ¹ Y ), the conformer with lower 

energy (the preferred conformer) is the one in which the larger group is equatorial. In cis-2methyl-1-cyclohexanol 

(X= OH and Y= Me), the methyl group is larger than the hydroxyl and 

the preferred conformation is the one in which the methyl group is equatorial. 

H 

H 

OH (a) 

2. trans-1,2-dimethylcyclohexane 

CH 3 (e) 

X 

H 

H 

Y 

(X = Y = Me) 

Two substituents on 1, 2-positions of a cyclohexane are said to be trans, if they occupy 

diequatorial (e,e) or diaxial (a,a) orientation, trans-1,2-dimethylcyclohexane exists in two 

energetically non-equivalent conformations- diaxial (a,a) (IIa) and diequatorial (e,e) (IIb) which 

are chiral (C2 symmetry). Unlike 1,2-cis, the trans-1,2-dimethylcyclohexane exists as a 

resolvable pair of enantiomers (racemte). The diequatorial conformation contains one gauchebutane 

interaction (e,e-Me), while the diaxial conformer contains four gauche-butane interactions 

(two for each axial methyl). As a result, the diequatorial form is preferred over diaxial form by 

three gauche-butane interactions (11.2 KJ/mol) corresponding to 99% of equatorial isomer. 

HO 

H 

CH 3 

239 

H


4 

4 

5 6 1 

H 

H 

5 

3 

3 

(IIa) 

5 

H 

CH3 

6 

2 

CH 3 

H 

H3C 2 

1 

CH3 (IIb) 

H 

trans 

3. 1,3-DISUBSTITUTED CYCLOHEXANE 

3. 1. cis-1,3-dimethylcyclohexane 

X 

H 

Y 

H 

H 

H 

5 

H 

H 

H 

H 

H 

(X = Y = Me) 

Two substituents occupying 1, 3-positions of a cyclohexane are said to be cis, if they 

occupy diaxial (a, a) or diequatorial (e, e) orientation. Cis-1, 3-dimethylcyclohexane exists as 

two energetically non-equivalent chair conformations (a, a and e, e) (III a & III b) which are 

achiral due to the presence of a s-plane ( º S1) (passing through C-2 and C-5) and so they 

constitute meso forms. The diequatorial conformer (III b) has no gauche-butane interactions 

while the diaxial form (III a) has two (one for each methyl) corresponding to an enthalpy of 

7.5KJ/mol and in addition a 1, 3-diaxial Me/Me interaction which contributes an additional 

energy of 15.5KJ/mol. The total enthalpy of diaxial isomer is thus 23.0KJ/mol higher than that 

of the diequatorial one. Hence the contribution of diaxial form is almost negligible to the 

equilibrium. 

4 

4 

3 

6 

6 

3 

2 

H 

H 

CH 3 

2 

CH 3 

1 

240 

H 

H 

CH 3 

CH 3 

1


4 

4 

H 3C 

5 

H 

3 

H 

CH 3 

3 

(IIIa) 

5 

6 

(IIIb) 

2 

6 

CH 3 

1 

H 

2 CH 3 

3. 2. trans-1,3-dimethylcyclohexane 

H 

1 

X 

H 

H 

Y 

H 

4 

H 

H 3C 

H 

CH 3 

3 

H 

4 

(X = Y = Me) 

Two substituents of cyclohexane ring occupying 1, 3-positions are said to be trans, if they 

bear axial-equatorial orientation. trans-1,3-dimethylcyclohexane exists as two nonsuperimposable 

chair conformations (a,e) (IVa & IV b) each with two gauche-butane interactions 

corresponding to an enthalpy of 7.5 KJ/mol and is less stable than 1,3-cis-isomer (e,e) by the 

same amount. 

H 

H 

3 

2 

5 

5 

2 

CH 3 

H 

1 

H 

H 

H 

6 

1 

H 

6 

241 

CH 3 

H


4 

H 

4 

3 

5 

H 3C 

CH 3 

5 

H 

3 

(IVa) 

(IVb) 

6 

6 

2 

CH 3 

1 

H 

2 CH 3 

H 

1 

Thus, unlike the 1,2 (also 1,4-) series, 1,3-cis is more stable than 1,3-trans-isomer. It is 

to be noted that trans-1,3-dimethylcyclohexane exists as a resolvable racemate [( ± )], since the 

chair inversion converts the molecule into an identical structure (unlike cis-1,2dimethylcyclohexane 

where chair inversion converts the molecule into its mirror image). 

When the two substituents are different (X ¹ Y) both cis and trans isomers are resolvable, 

the former (cis) exists in the predominantly diequatorial form and the latter (trans) in the 

equatorial –axial conformation with bulkier group occupying equatorial position. 

The preferred diequatorial conformation of cis-1,3-isomer is not suitable for certain 

reactions (eg. anhydride formation, hydrogen bond formation between 1,3-groups etc.) as the 1,3groups 

are far apart in this conformation. However, ring inversion of the diequatorial form 

converts it into a diaxial conformation in which 1,3-groups are close to each other, The 

formation of anhydride from cis -1,3–cyclohexanedicarboxylic acid (V) and the intramolecular 

hydrogen bond formation in cis-1,3-cyclohexane diol (VI) takes place through the diaxial 

conformations (V b & VI b) of 1,3-cis-isomer. 

H 3C 

H 

H 

4 

H 

4 

H 

3 

H 

H 

3 

CH 3 

2 

5 

5 

2 

CH 3 

H 

H 

H 

1 

1 

H 

6 

6 

242 

H 

CH 3 

H


HOOC 

HO 

H 

H 

H 

COOH 

(Vb) 

(VIa) 

(Va) 

COOH 

H 

1, 4-Disubstituted cyclohexanes 

i) Cis-1, 4-dimethylcyclohexane 

Y 

H 

H 

H 

OH 

COOH 

X 

H 

D 

-H 2O 

(X = Y = Me) 

H 

H 

OC 

O 

O 

H 

(VIb) 

Two substituents on 1, 4-position of a cyclohexane ring are said to be cis, if they bear 

axial-equatorial orientation. Cis- 1, 4 –dimethylcyclohexane exists in two identical (a, e) and (e , 

a) conformations (VII a & VII b). A vertical s-plane passes through 1,4–positions and so all 

conformations are achiral even when the two substituents are different. When both substituents 

are different (X ¹ Y), the cis–isomer exists in two unequally populated conformers, the 

preferred conformer is the one with bulkier group in equatorial position. 

CO 

O 

243 

H 

H 

H


H 3C 

H 

CH 3 

4 

4 

H 

3 

5 

5 

3 

(VIIa) 

(VIIb) 

6 

s 

2 

CH 3 

1 

H 

2 

1 

CH3 H 

ii) trans – 1, 4 – dimethylcyclohexane 

6 

s 

H 

Y 

X 

H 

CH 3 

244 

H 

H3C 3 

H 

5 4 

2 1 

H 

H 

6 

H 

H 

H 

H 

4 

(X = Y = Me) 

Two substituents occupying 1, 4 – positions of a cyclohexane ring are said to be trans, if 

they bear diaxial or diequatorial orientation. Trans -1, 4 – dimethylcyclohexane exists in two 

non – equivalent diequatorial (VIII a) and diaxial (VIII b) conformers, of which the latter (a, a) 

(VIII b) is destabilized by four gauche – butane interactions (15.0 KJ/mol). Both conformers are 

achiral as a plane of symmetry passes through 1, 4 – positions. 

The trans -1,4–isomer is preferred over the cis – 1, 4 by two gauche – butane interactions 

while trans – 1,4– has none. When both substituents are different (X ¹ Y), the trans– 1,4 isomer 

exists predominantly in diequatorial conformation. 

CH 3 

H 

3 

2 

5 

H 

H 

1 

6 

H 

CH 3


H 3C 

H 

4 

4 

H s 

CH 3 

3 

5 

5 

3 

(VIIIa) 

6 

2 

1 

CH3 H 

6 

(VIIIb) 

2 

CH 3 

20.6. DECALINS: Bicyclo [4.4.0] decane 

s 

1 

H 

H 

H 3C 

H 

4 3 

H 

2 

5 

H 

H 

1 

6 

H 

CH 3 

245 

CH 3 

H 

H 

3 

H 

5 4 

2 1 

H 

CH3 6 

H 

H 

A fused ring system is one in which adjacent rings have two atoms in common. By for the 

most important fused ring system is the decalin which exists in two diastereoisomeric forms, the 

cis and the trans. If cyclohexane ring system were to be planar as suggested by Baeyer, only one 

form of decalin with ring system junction hydrogens projecting on the same side of the molecule 

should exist. On the other hand, Sachse –Mohr concept of puckered rings permits the existence 

of two isomeric forms of decalin. In fact, Mohr predicted that two isomeric forms of decalin 

molecule should exist before W.Huckel succeeded in preparing them. Both isomeric forms of 

decalin occur in petroleum ether. 

20.6.1. GEOMETRY 

The cyclohexane rings in both cis and trans-decalins exist in chair conformation. Cisdecalin 

(I) is formed when both cyclohexane rings are joined through axial-equatorial bonds, 

whereas, the trans-decalin (II) is produced by joining the two cyclohexane rings through 

equatorial bonds only. Trans-decalin (II) has rigid geometry and cannot undergo ring inversion 

which would lead to a highly strained ring system with diaxial fusion. In contrast, cis decalin in 

which two cyclohexane rings are fused through axial-equatorial bonds can readily undergo ring 

inversion by exchanging a,e bonds at ring junction. The two interconvertible chair conformations 

(Ia & Ib), similar to cis-1,2-dimethylcyclohexane are equienergetic and so equally populated at 

room temperature. as in the case of cis-1,2- dimethylcyclohexane, the ring inversion converts one 

conformer into its mirror image; cis-decalin (I) is therefore, a non-resolvable racemate( ± ).


3 

3 

2 

2 

7 

4 

6 

(Ia) 

20.6.2. SYMMETRY 

4 

1 

1 

H 

(II) 

8 

5 

10 

9 

10 

9 

H 

H 

1 

4 

2 

3 

(I) (II) 

H 

H 

10 

8 

9 

5 

8 

6 

5 

H 

6 

7 

7 

C 2 

7 

6 

H 

2 

H 

8 

5 

H 

2 

H 

9 

10 

H 

H 

H 

H 

3 

H 

H 

4 

1 

1 

4 

H 

2 

3 

H 

H 

6 

H 

7 

8 

10 9 

The conformation of trans-decalin (II) has a centre of symmetry (mid point of 9-10 bond) 

and is achiral. In addition, it possesses a C2 axis passing through C2-C3 ,C9-C10 and C6-C7 bonds 

and a s-plane perpendicular to C2 axis and passing through the ring junction .It belongs to C2h 

point group and its symmetry number is 2. On the other hand, the individual conformations of 

cis-decalin molecule are chiral as they are devoid of mirror symmetry. They have a C2 axis 

passing through the mid point of C9-C10 bond and bisecting the dihedral angle between 9-H and 

10-H. Their symmetry number is also 2 and belongs to C2 point group. 

Since the two individual conformations of cis-decalin are enantiomeric and equienergetic 

they are readily interconvertible at a rate too fast to separate them. So cis –decalin molecule is a 

non-separable racemate. 

3 

4 

1 

9 

H 

H 

10 

H 

C 2 

5 

5 

8 

H 

H 

H 

6 

246 

H 

7 

H


3 

3 

2 

2 

4 

(Ia) 

1 

1 

H 

10 

10 

4 9 

C 3 

5 

(Ib) 

20.6.3. ENTHALPY AND FREE ENERGY 

6 

9 

8 

H 

6 

5 

H 

7 

8 

7 

enantiomers 

7 

H 

6 

5 

8 

9 

10 

H 

(Ib) 

The difference in enthalpy between cis- and trans-decalins can be determined by 

counting the number of gauche-butane interactions. In trans-decalin, since each ring is fused 

through the equatorial bonds, no gauche- butane interactions exist. In cis-decalin, there are three 

such interactions and the difference in enthalpy is therefore amounts to 10.5 KJ/mol 

(3´ 3.3 KJ/mol).Therefore, trans-decalin is more stable than cis. 

1 

4 

2 

247 

3


3 

2 

4 

20.6.4. EFFECT OF ANGULAR METHYL GROUP 

1 

H 

10 

8 

9 

6 

5 

H 

7 

Gauche units 

1-2/9-8 

4-10/5-6 

4-10/9-8 

Introduction of a methyl group at one of the fused carbon atoms as in steroids (C-9 or 

C-10) gives rise to additional gauche-butane interactions and consequently the potential energy 

difference between cis- and trans-9-methyldecalin system (III &IV) is less than that of cis- and 

trans- decalin (I &II). The angular methyl group in trans-9-methyldecalin (IV) is axial and gives 

rise to four butane-gauche interactions (two with respect to each ring). In cis-9-methyldecalin 

(III), the 9- methyl group is axial with respect to one ring only and equatorial with respect to the 

other, giving rise to two gauche-butane interactions in addition to three already present in cisdecalin.Thus, 

the total number of gauche butane interactions in the cis-compound is therefore 

five that is one more than the trans-isomer. Thus, the original difference between cis and trans- 

decalins is reduced to one in 9-methyldecalin in favor of the trans-isomer which is more stable 

than the cis-isomer by 3.35 KJ/mol. 

3 

2 

4 

1 

H 

8 

10 

(IIIa) 

9 

6 

5 

Me 

7 

enantiomers 

7 

Me 

6 

5 

8 

9 

10 

H 

(IIIb) 

1 

4 

2 

248 

3


3 

2 

4 

1 

H 

10 

Me 

9 

cis (IV) 

Trans-9-methyldecalin (IV) does not have any C2-axis but possesses a plane of symmetry 

(s) passing vertically along 9-10 bond and hence achiral (Cs point group).The individual 

conformations of cis-9-methyldecalin (IIIa &III.b) are chiral as they are devoid of mirror 

symmetry (C1 point group) and constitute a pair of equienergetic enantiomers.However, the two 

enantiomers are readily interco0nvertible by ring inversion and cis- isomer is thus a nonseparable 

racemate ( ± ). 

20.7. CONFORMATIONS OF PERHYDROPHENANTHRENE 

Among the fused tricyclic system, the perhydrophenanthrene molecule is interacting in 

that it illustrates many stereochemical aspects of polycyclic natural products such as steroids and 

triterpenoids. Perhydropherianthrene molecule contains four like chiral (ABAB) and so exists as 

two meso and four racemates (the number of chiral centers is even and so the number of meso 

forms is 2 (4-2)/2 = 2 and the number of optical active forms is 2 (4-1) = 2 3 = 8 which forms four 

racemates). The six diastereoisomeric forms are shown along with their conformational 

representations (for chiral forms, only one enantiomers of each (± ) -form is drawn). 

The prefixes cis and trans are used to denote the stereochemistry of fusion of terminal rings 

( A and C ) to the central ring (B) , whereas syn and anti are used to indicate the orientation of 

terminal rings (A and C) with respect to each other ( that is by considering the relative position of 

hydrogens at C – 12 and C – 13 . The prefixes syn and anti are used when these hydrogens are 

on the same or opposite side respectively). A heavy dot indicates that the hydrogen atom is 

above the plane of the ring system whereas the absence of a dot indicates that the hydrogen is 

below the plane of the ring system. The relative stabilities of the six diastereoisomers have been 

assessed by counting butane – gauche interactions. 

5 

8 

6 

7 

249


6 

7 

A 

5 

H 

H 

H 

4 

C 

12 

A 

13 

14 

B 

11 

8 

B 

9 

3 

C 

10 

H 

trans-anti-trans( )-(4e) (I) 

± 

A 

A 

H 

H 

H 

B 

B 

C 

C 

2 

1 

H 

(±) -cis-anti-trans(3e + 1a) (II) 

7 

6 

A 

H 

13 

5 

B 

e 

8 9 

14 

H 

H 

12 

H 

4 

10 

number of gauche interactions = 

(1+0) = 3.35 KJ/mole 

e 

A 

a 

H 

B 

e 

H 

H 

11 

3 

e C 

H 


(1+3) = 13.4 KJ/mole 

e 

C 

e 

1 

250 

2


A 

A 

H 

H 

H 

B 

B 

C 

C 

H 

(±)-cis-syn-trans(3e + 1a) (III) 

A 

A 

H 

H 

H 

B 

B 

C 

C 

H 

(±) -cis-anti-cis(2e + 2a) (IV) 

H 

H 

6 

4 

A 

e 

a 

e 

5 

a 

e 

3 

A 

H 

H 

12 

8 

7 

2 

C 

B 

H 

11 


(1+3) = 13.4 KJ/mole 

H 

B 

B 

H 


(0+6) = 20.1 KJ/mole 

A 

a 

e 

9 

e 

1 

C 

10 

H 

251


A 

A 

A 

A 

H 

H 

H 

B 

B 

C 

C 

H 

cis-syn-cis (2e + 2a)(meso) (V) 

H 

H 

13 

H 

B 

B 

9 

12 C 

s 

C 

10 

trans-syn-trans (meso) 

(4be) 

(VI) 

H 

s 

8 

A 

9 

7 

10 

H 

H 

a 

14 

B 

A 

H 

6 

e 

a 

H 

H 

e 

H 

e 

H 

enantiomers 

(30.1 KJ/mole) 

5 

B 

11 12 

H 

H 

23.4 KJ/mole 

13 

C 

1 

C 

4 

a 

H 

H 

2 

3 

252


Johnson predicated the relative stabilities of the six diastereoisomers on the basis of the 

following assumptions: 

i) The system in which the central ring (B) is fused to other rings by larger number of 

equatorial bonds is more stable. 

ii) In case when axial bonds of the central ring (B) are used in ring fusion , 1,2– and 1,4– 

diaxial arrangements are preferred over 1,3–diaxial which h suffers from a severe 1,3– 

diaxial methylene interaction. 

iii) Regardless of the assumption 1 and 2, if the central ring junction involves two axial 

bonds either way the system is labeled, the central erring cannot exist in chair form but 

adopts a boat or twist – boat conformation. 

Based on these assumptions, the stabilities of the six diastereoisomers are assessed. 

a) The trans–anti–trans isomer (I) is the most stable in which the central ring (B) is 

fused to the other rings (A and C) by four equatorial bonds. However, unlike the trans– 

decalin, this system has one gauche–butane interaction resulting from hydrogen on C–4 

and C–5 (4,5- interaction) (Although two adjacent e,e or a,e bonds of cyclohexane ring 

form a gauche – butane interaction, this interaction is present in all isomers). 

b) The cis–anti–trans isomer (II) has a cis–decalin unit involving three gauche–butane 

interactions, in addition to the 4,5–interaction. So its estimated energy is 13.4 KJ/mol 

(4´3.5 KJ/mol). 

c) The situation is same in case of cis–syn-trans isomer (III), the 4,5–interaction is due to 

a,e – substitution. 

d) The cis–anti–cis isomer (IV) is flexible can undergo ring inversion to give energetically 

non–equivalent conformers A and B. 

e) The cis-syn-cis isomer (V) also exists as a mixture of two equienergetic conformations 

and like cis-decalin is an inseparable racemate. The planar structure contains a s -plane 

and hence it is designated as meso. In addition to the usual 4,5 – interaction, this isomer 

has two cis-decalin units and a 1,3-syn diaxial interaction (22.6KJ/mol), so the total 

energy of this isomer is 29.3 KJ/mol. 

f) The trans-syn-trans isomer (VI) cannot have both ring junctions trans-fused with cisorientation 

of 12-13 and 11-14. In order to achieve this geometrical requirement, the 

central ring (B) adopts a boat conformation with terminal rings fused through four boat 

equatorial (be) bonds. The estimated energy of this isomer is 23.4 KJ/mol and is achiral. 

The planar structure shows a plane of symmetry passing through 9–10 and 12–13 bonds. 

253


20.8. CONFORMATIONS OF PERHYDROANTHRACENE 

In perhydroanthracene molecule, the three rings are fused in a linear manner. The four 

chiral centres are equivalent and correspond to AAAA type so that the number of isomers is less 

than predicated. Perhydroanthracene exists as five diastereoisomers: trans-syn-trans (meso) (I), 

cis-syn-trans (II), cis-anti-cis (meso) (III), trans-anti-trans (IV) and cis-syn-cis(meso) (V). It 

must be noted that the cis-syn-trans (II) may well be called cis-anti-trans depending on whether 

one looks at the bridgehead atoms in clockwise or anticlockwise direction. 

A B C 

trans-syn-trans (meso) 

(4e) 

(I) 

A B C 

cis-syn-trans (±) 

(3e) 

(II) 

H 

A 

e 

e 

H 

B 

H H 

H 

no of gauche interactions = 0 

A 

e 

a 

H 

B 

H 

e 

H 


(10.05 KJ/mole) 

e 

e 

e 

C 

C 

254


A B C 

cis-anti-cis (meso) 

(2e) 

H 

(III) 

A B C 

trans-anti-trans (±) 

(4be) 

(IV) 

H 

H H 

A B C 

cis-syn-cis (meso) 

(V) 

H 

A 

H 

e 

a 

H 

H 

A 

e 

H 

B 

e 

B 

H 

C 

a 

H 

255 


(20.10 KJ/mole) 

H H 

> 23.4 KJ/mole 

a 

> 35.0 KJ/mole 

H 

H 

C 

H




Pointed out 

Ø Conformations of ethane 

Ø Conformations of 1,2–dihalogenoethanes 

Ø Conformations of cyclohexane 

Ø Geometry of the cyclohexane ring system 

Ø Equatorial and axial bonds 

Ø Ring inversion 

Ø Flexible conformations 

Ø Conformations of mono and di-substituted cyclohexanes 

Ø Monosubstituted cyclohexane 

Ø Disubstituted cyclohexanes 

Ø 1,2–disubstituted cyclohexane 

Ø Decalins: bicyclo [4.4.0] decane 

Ø Conformations of perhydrophenanthrene 

Ø Conformations of perhydroanthracene 


1. Although, the anti conformation of n-butane is more stable than the gauche, in case of 

2, 3-dimethylbutane, the population of gauche forms is twice that of anti. Explain. 

2. Explain the greater population of the anti-conformation of 1, 2-dibromoethane (83%) 

relative to the anti-conformation of n-butane (67%). 


1. Discuss the conformations of acyclic and cyclic molecules. 

2. Of cis- and trans- decalin which is more stable and why? 

3. Of cis- and trans- 1,3-dimethyl cyclohexanes, which is more stable and why? 

4. Draw the conformations of perhydrophenanthrene. 

5. Draw the conformations of perhydroanthracene. 





1992. 


1991. 

256

aromaticity

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