1. Compare the dipole moment of 1,2-dibromocyclohexane.

Let us see the structure of cis and trans isomer of 1,2-dibromocyclohexane.

In case of cis isomer the dihedral angle between two C-Br bond is 60° for both the
conformer. So the observed dipole moment (µobs=3.12D) and calculated dipole moment (µcal=
3.09D) are very close.
H H
1 H 1 Br
Br H Br H
H Br
2 2 1 2 2 1
Br H H
Br Br Br
(e, a) (a, e) (e, e) (a, a)
cis-1,2-dibromocyclohexane trans-1,2-dibromocyclohexane
Br
Br
Br Br Br
Br Br Br
0 0 0 0
But in case of trans isomer, in one conformation the dihedral angle between two C-Br bond is
60° but for other conformer it is 180°. So the µobs will be the average of the corresponding
population % of the conformers and which is 2.11D. In the case of e,e conformer µcal is
3.09D but for a,a conformer it is zero. But the observed µ is greater than the mean value of
the two conformer and this indicate that the % population of e,e conformr is much more than
a,a conformer.

2. Compare the acid strength of cis and trans isomer of cyclohexane-1,2-dicarboxylic

acid.

(Explain the fact that the differences between two pKa of cyclohexane-1,2-
dicarboxylic acid is greater for cis isomer than the trans isomer.)

In case of cis-cyclohexane-1,2-dicarboxylic acid the first ionisation will be very fast as the
corresponding conjugate bases will be highly stable due to formation of intramolecular H-
bonding. Hence the pKa1 will be of low value and it will be same for the both conformer as
the possibility of intramolecular hydrogen bond formation is equal in both conformer. Due to
same reason, i.e, intramolecular H-bonding, the second ionization (pKa2) will be slow and
hence pKa2 will be high. As a consequence the difference between pKa2 and pKa1 will be
high.

In trans isomer although pKa1 is same for the both conformer but the value of pKa1 is high
as there is no possibility of intramolecular H-bond formation after first ionization. Similarly
the pKa2 will be low as second ionization will be easy. So the difference between pKa2 and
pKa1 will be less.
 H H
1 H 1 COOH
COOH H COOH H
H COOH
2 2 1 2 2 1
COOH COOH H H
COOH COOH
(e, a) (a, e) (e, e) (a, a)
cis-cyclohexane-1,2-dicarboxylic acid trans-cyclohexane-1,2-dicarboxylic acid

-H+ -H+ -H+ -H+

pKa1 pKa1 pKa1 H pKa1
H
O H COO
H COO H
H COOH
O O
H H
H O COOH
O O
O
H O
intramolcular H-bond

3. Compare the acidity of cis and trans isomer of 4-t-butylcyclohexane carboxylic acid.

Due to the presence of tertiary butyl group at 4 position the conformation of the above
compound will be locked and the t-butyl group will be at equatorial position. Here the
conjugate base of the trans isomer will be more stable as the carboxylate anion at equatorial
position will be more solvated and hence will be more stable compared to axial carboxylate
group (cis isomer). For better solvation the water molecules can easily acess the less hindered
equatorial position. So trans-4-t- butylcyclohexane carboxylic acid is more acidic compared
to the cis isomer.

COOH H
CH3 CH3
H3C H3C
H COOH
H3C H3C
cis-4-t-butylcyclohexane carboxylic acid tras-4-t-butylcyclohexane carboxylic acid

-H+ -H+
O
O H
CH3 CH3 O
H3C H3C
H
H3C H3C O

4. Compare the basicity of cis and trans isomer of 4-t-butylcyclohexyl amine.

Due to the presence of tertiary butyl group at 4 position the conformation of the above
compound will be locked and the t-butyl group will be at equatorial position. Here the
conjugate acide of the trans isomer will be more stable as the protonated amine at equatorial
position will be more solvated and hence will be more stable compared to axial counterpart
(cis isomer). For better solvation the water molecules can easily acess the less hindered
equatorial position. So trans-4-t- butylcyclohexyl amine is more basic compared to the cis
isomer.

NH2 H
CH3 CH3
H3C H3C
H NH2
H3C H3C
cis-4-t-butylcyclohexyl amine tras-4-t-butylcyclohexyl amine

5. Compare the rate of chromic acid oxidation of cis and trans 4-t-butylcyclohexanol.

Let us have a close look on chromic acid oxidation of a secondary alcohol-

O O ‘
CrO3 r.d.s
OH O Cr OH O + Cr
slow HO OH
H H O
secondary alcohol chromate ester keotne
H2 O

OH H
CH3 CH3
H3 C H3C
H OH
H3C H 3C
cis-4-t-butylcyclohexanol tras-4-t-butylcyclohexanol

CrO3 O CrO3
H2O
O Cr OH H O
CH3 high enery CH3
H3 C O H3C
H chromate ester O Cr OH
as more 1,3-diaxial
O
H3C H2O interaction H 3C

O
OH2
O Cr OH H O
CH3 CH3
H3C O stabilised T..S. H3C
H as more strain O Cr OH
OH2 released O
H3C T.S. H3C
T.S.

CH3 O CH3 O
H3C H3C

H3C H3C
4-t-butylcyclohexanone 4-t-butylcyclohexanone
The reactive species in the chromic acid oxidation is Cr(VI) oxidewhich form a chromate
ester at first step. Water molecule at second step abstract the proton and gives the oxidised
product ketone. The second step is the slowest step and rate determining step. In this step a
bulky chromate ester is converted to a simple ketone and hence steric strain is released in this
step.

If we compare the oxidation of cis and trans isomer of 4-t-butylcyclohexanol, in each case
the starin will be released at r.d.s.. But the extend of strain release will be more in cis isomer
(axial chromate ester) as the T.S. will be more stabilised compared to trans isomer. If we see
the realative energy profile diagram of this step, the chromate ester (reactant) of the cis
isomer have much more energy compared to the trans ismer as the bulky chromate ester
group experience much more diaxial interaction at axial position. At T.S. where the chromate
ester bond breaking happening, the strain release will be much more for cis isomer and hence
the T.S. of the cis isomer will be much more stable compared to the trans isomer. Hence the
activation energy (Eact) which is the difference between reactant and T.S. will be less for cis
isomer and so the oxidation rate is faster for cis isomer.

6. Compare the chrmic acid oxidation rate of this two alcohol.

CH3 H CH3 OH

H3 C OH H3 C H
H3 C H3 C
1.87 62.7
 7. Compare the rate of hydrolysis of cis and trans isomer of ethyl 4-t-butylcyclohexane
carboxylate.

In case of base catalysed ester hydrolysis, the attack of base (-OH) on the carbonyl group of
ester is the r.d.s. Here steric crowding is increasing during the attack of the base as the sp2
carbonyl is being converted to sp3 tetrahedral centre. So, the T.S. of the r.d.s. will be of high
energy as the steric crowding increases. Now the energy of the T.S. of cis isomer (axial ester)
will increase much more compare to the trans isomer (equatorial ester). So eventually the
Eact for cis isomer will be much higher compared to the trans isomer and hence cis isomer
will react slowly in base catalysed ester hydrolysis.

COOEt H
CH3 CH3
H3C H3C
H COOEt
H3C H 3C
Ethyl (cis-4-t-butylcyclohexane) carboxylate Ethyl (trans-4-t-butylcyclohexane) carboxylate
-
OH -
OH
r.d.s
r.d.s
OEt
O
H
CH3 OH CH3
H3C H3C O
H
H3C H 3C HO OEt

O O H
CH3 CH3
H3C H3C O
H
H3C H 3C O
 8. Explain this ratio of base catalysed ester hydrolysis between cis and trans isomer of
two different compound.

O
CH3 CH3
H3C O NO2 H3C O CH3
O
H3C H3C

Rate of hydrolysis (ktrans/kcis)2.25 Rate of hydrolysis (ktrans/kcis)20

In first example the substrate ester is formed by acid of para-nitrobenzoic acid and
substituted cyclohexanol. This implies that the carbonyl centre is apart from the cyclohexane
system by a oxygen atom. So during base catalysed hydrolysis the more crowded tetrahedral
T.S. formed is located somehow apart by an oxygen atom from cyclohexane system and
hence relative diaxial interaction which will be experienced by axial ester isomer will be not
that much effective to increase the activation energy. This phenonomenon explain only 2.25
times increased ester hydrolysis rate for the trans isomer over cis.

On the other hand in second compound the ester is being formed by substituted cyclohexane
carboxylic acid and para cresol and hence the carbonyl carbon is directly attached to
cyclohexane ring. So during base catalysed hydrolysis the more crowded tetrahedral type T.S.
formed is very close to the cyclohexane ring and as a consequence for axial (cis) isomer
during hydrolysis the energy of T.S. increases tremendously. Thus the reaction rate slows a
lot and hence reaction rate ration of trans isomer increases dramtically over cis isomer.

125 -
9. Compare the rate of substitution reaction by I with cis and trans isomer of 4-t-
butylcyclohexyl iodide.
In this case the nucleophile and the leaving group is same and hence the T.S. will be identical
for both cis and trans isomer which indicate that the energy of the T.S. is same for both
isomer. Actually in a typical SN2 reaction in a cyclohexane system when the leaving group is
at equatorial position, nucleophile attacks from axial side and vive versa. Here the energy of
the cis isomer where large iodide group is at axial position is high compared to the trans
isomer due to 1,3 di-axial interaction. So the effective activation energy for cis isomer will be
less than the trans isomer and hence cis isomer will react at faster rate compared to the trans
isomer.

I I H
CH3 CH3 H CH3
*I
H3C H3C H3C
H * I*
H3C I
H3C T.S. (cis) H3C
cis-4-t-butylcyclohexyl iodide

I
H I* I*
CH3 * CH3 H CH3
H3C I H3C H3C
I H
H3C I
H3C T.S. (trans) H3C
trans-4-t-butylcyclohexyl iodide

10. Compare the rate of substitution reaction of cis and trans isomer of 4-t-
butylcyclohexyl bromide with sodium thiophenoxide.

In this case the size of the nucleophile (-SPh) is greater than the leaving group (Br-). So
during substitution reaction the axial approach of the nucleophile will be of higher activation
energy as larger nucleophile will experience much 1,3-di-axial interaction. This happen for a
trans isomer where leaving group is at equatorial position. Now if we compare the energy of
reactant, obviously the energy of cis isomer will be larger than the trans isomer. All these
phenomenon tells that the effective activation energy for cis isomer is less compared to the
trans isomer and hence the reaction rate is much more.

CH3 I CH3 PhS

H H
H3C H3C
SPh I
H3C T.S. (cis) H3C T.S. (trans)- high energy

11. Compare the rate of substitution reaction of 4-t-butylcyclohexyl tosylate with sodium
thiophenoxide.

In this case the size of nucleophile (-SPh) is smaller than the leaving group (-OTs). So during
substitution reaction the equatorial approach of the nucleophile will be of higher activation
energy as larger leaving group will experience much 1,3-di-axial interaction. This happens
for a cis isomer where leaving group is at axial position. Now if we compare the energy of
reactant, obviously the energy of cis isomer will be larger than the trans isomer. These entire
phenomenon tells that the effective activation energy for cis and trans isomer is comparable
and hence the reaction rate is comparable.

CH3 TsO CH3 PhS

H H
H3C H3C
SPh OTs
H3C T.S. (cis)- high energy H3C T.S. (trans)
 12. Predict the product of the following reaction-

NaOEt NaOEt
? ?
EtOH EtOH
Cl Cl

This reaction is an example of 1,2-elimination reaction where abstracting hydrogen and the
leaving group must be anti-periplaner to fulfil the condition of a typical E2 reaction.

Hb
H3C CH3


Ha OEt H CH3
Hb -HaCl
CH3
 H3C
Ha
-HbCl
Cl H CH3 CH3
Cl OEt H3C

CH3

For this isomer there is two anti hydrogen present corresponding to the leaving group
chlorine, so reaction can follow either route to give two different product.
 CH3 CH3
Cl
CH3
 H3C H 
Cl
Cl CH3 flipping
H H
no anti hydrgen for elimination H3C CH3 H3C CH3

Whereas in this isomer there is no anti hydrogen for elimination but after flipping there is
only one anti hydrogen for elimination and hence we get only one product. Point to note that
although the fliiped conformer is very higher energy and hence % population is very less but
once the reaction starts, equilibrium drives towards the product.

13. Explain what will happen when p-toluenesulphonates of cis and trans 2-p-
toluenesulphonylcyclohexanol is reacted with NaOH?

In cis isomer the leaving group tosyl and hydrogen atom is perfectly anti position for a E2
elimination and we got the desire product.

H
SO2Ar
OH
SO2Ar SO2Ar 
H NaOH
OTs

In trans isomer, there is no anti hydrogen for elimination but after flipping the flipped
conformer have one anti hydrogen and we should expect this product which is different from
previous product.

H
OTs SO2Ar
NaOH H
SO Ar H 
OTs 2 flipping H OH
H SO2Ar
H H SO2Ar
no anti hydrgen for elimination but this product donot formed

However in reality we do not get this product rather we get a similar product as obtained
from cis isomer. Actually for the trans isomer the flipping does not happen as two bulky
group cant be at axial position and hence the reaction follow a different mechanistic pathway.
Due to presence of a strong electron withdrawing group –SO2Ar, the reaction follows E1CB
mechanism.

H
OH SO2Ar
SO Ar SO Ar SO2Ar 
OTs 2 NaOH OTs 2
H H
 14. What will happen when cis and trans isomer of 4-t-butylcyclohexyl amine is treated
with NaNO2/HCl?

NH2 N2
NaNO2
HCl H 
H H

cis-4-t-butylcyclohexyl amine H

In this reaction the primary amine will react with sodium nitrite in presence of HCl to give

–N2+ which is highly unstable. In case f cis isomer, the N2+ have a anti H to elimate and
ultimately we got a alkene.

H H H H
NaNO2

NH2 HCl N2 H2O OH

trans-4-t-butylcyclohexyl amine

But the trans isomer don’t have any anti H corresponding to -N2+ group and hence we got a
substitution product alcohol.

15. Compare the rate of reaction of cis and trans isomer of 1,2-dibromocyclohexane with
NaI.

H
Br
NaI
Br H
Br I
H
H ring inversion Br
trans isomer

H H
I
NaI NaI
Br Br
H I H
I I
H
Br H ring inversion Br
cis isomer

In both cases the product is same cyclohexene but the cis isomer react much more faster rate
compared to trans isomer. In cis isomer first the nucleophile iodide replace axial bromide and
then a ring inversion followed by elimination gives cyclohexene. This is nucleophilic
catalysis and hence reaction rate is high for a low activation energy.

The diequatorial trans conformer after flipping take part in direct elimination reaction to form
cyclohexene.

16. Explain the reaction of 2-bromo-4-phenylcyclohexanol with either NaOH or Ag2O.

Let us see how different stereoisomer of the above compound behaves with either base or
silver oxide.

O H

Ph OH
OH
O O
Br
H Br
NaOH Ph 
OH
Ag2O H
Ph Ph
Ph

H Br
Ag

Ph O H O
OH OH
Br O
H Br
NaOH Ph 
H
Ag2O
Ph H H
Ph O Ph

H Br
Ag

Ph
Br
O H OH
OH
OH H O
OH H Ph
Br
Ph flipping Ag
H Ph 
 Br
Br
H O H O
Ag2O
Ph Ph
H
H
 Ph Ph
Br
H  O
OH
H OH O
OH H O H
flipping Ph
Br
Ph OH
Br CHO
H H
H
Ag2O Ph Ph
Ph Br
O H O 
Ag
H H Ph

17. Explain the reaction with product-

Ph  Ph 

? ?
OC(S)SMe OC(S)SMe
1

These two compounds are in xanthate class and hence upon heating they will follow pyrolytic
elimination to give alkene. This reaction is a syn elimination where a syn hydrogen at beta
position with respect to the xanthate group is necessary to fulfil the mechanism of the
reaction. A general mechanism is as –
1

KOH CH3I
CS2
H OH H O H O H O
S H O
S S
S SMe SMe S
SMe

MeSH S C O

Ha Ph
Hb Hb
Ph S -OC(SMe)SHa Ph 
O C
Ph H H
SMe
 Ha Ha Ph
Hb
OC(S)SMe Ph S -OC(SMe)SHb Ph
O 
trans isomer C
H
SMe
two possible syn hydrogen for elimination two possible product
In case of trans isomer (e,e conformer), there is two possible syn hydrogen present with
respect to the xanthate group and hence elimination could take part with either hydrogen to
give rise two different product.
H H
H Ph
Ph
Ph -OC(SMe)SH Ph
 H 
H
OC(S)SMe O
S C
SMe
only one syn hydrogen for elimination only one product

Whereas in cis isomer there is only one syn hydrogen with respect to the xanthate group and
hence only one product we got by elimination.

18. Predict the products that will be formed when different isomers of 2-
aminocyclohexanol will react with NaNO2 and HCl?

H H H CHO

NH2 NaNO2 N2

NH2 H HCl H H
OH OH O O
OH H H
NaNO2
cis-isomer H H
HCl
HO HO O
NH2 N2

O
NH2 N2

H NaNO2 H
NH2 OH HCl OH
H H O
CHO
OH OH OH O
NaNO2
cis-isomer NH2 N2
HCl
H H
H H

H H H CHO

NH2 NaNO2 N2

NH2 OH HCl OH O
H H H
OH OH OH O
NaNO2
trans-isomer H H O
HCl
H H
NH2 N2
 NH2 N2

H NaNO2 H O
NH2 H HCl H
OH OH O
CHO
OH H H H
NaNO2
trans-isomer NH2 N2
HCl
HO HO O
H H

19. Predict the products when different isomers of 1,2-dimethylcyclohexane-1,2-diol

reacted with 60% H2SO4?

CH3 CH3
OH OH
CH3 OH
OH CH3

CH3 CH3 CH3 CH3 O

+ +
OH2 +H OH +H OH
CH3 CH3 CH3 CH3 CH3


O OH OH OH2  CH3
CH3 O

COCH3 CH3

 CH3
H3C CH3 CH3 CH3 
CH3 CH3 +H+ CH3 +H+ CH3 CH3

OH2 OH HO O
O OH OH OH2 CH3

CH3 CH3 CH3 CH3 CH3

OH2 +H+ OH +H
+
OH O
CH3 OH OH OH2


O CH3 CH3 CH3  CH3

CH3 CH3
COCH3 COCH3

CH3 OH2 OH OH
CH3 +H+ CH3 O
CH3 CH3 +H+ CH3
H3C H3C H3C
OH OH OH2 H3C
O
 CH3 
CH3
O
O
CH3
CH3
 20. Predict the product of the following reaction-
O
H H
NaNO2 O
OH OH 
H HCl H

NH2 N2

OH OH O
CHO
NaNO2
H H H 
NH2 HCl N2

H H

H H O
CHO
NaNO2
OH OH H 
NH2 HCl N2

H H

O
OH OH
O
NaNO2
H H 
H HCl H

NH2 N2

21. Explain the observation of these reaction-

OTs OAc OTs OAc

NaOAc NaOAc
AcOH AcOH
OAc OAc OAc OAc
Optically active (cis) Optically active (trans) Optically active (trans) (/-) racemic mixture

This reaction is a example of substitution reaction where in first example (cis isomer) a direct
SN2 reaction happen by -OAc nucleophile and tsylate acts as a leaving group. A direct
inversion of an optically active compound leads to an optically active product (stereospecific
reaction).

OTs H
OTs OAc
SN2 (inversion) OAc
 H 
OAc OAc
OAc OAc OAc
H H
Optically active (cis) Optically active (trans)
stereospecific reaction
In case of the trans isomer, the ee conformer flipped to aa conformer and geometrically acetyl
group is perfectly aligned to take part in a SN2 reaction from back side of tosyl group which
is known as neighbouring group participation. In second step outside nucleophile –OAc can
attack on any carbon in a SN2 manner to give a racemic mixture.

H CH3 CH3 CH3

OTs
OTs O O O
OAc O NGP O O
H SN2 H
OAc OAc
H H (inversion) H
Optically active (trans) OTs H H
OAc
OAc
H3C O
H H
H
O OAc
 AcO OAc
AcO
AcO
H H H
(/-) racemic mixture

22. Predict the product f the following reaction?

OBs O
Ph KOAc OBs  O S Br
AcOH
O18 O
O
This is a substitution where brosylate group will be replaced by acetyl group. Here NGP will
also take place followed by attack by acetate group. Here as one oxygen is lebbeled, final
distribution of the lebelled oxygen will be like this. Obviously we will get a racemic mixture
but scrambling lebelled oxygen will take place. This is an evendence in favour of NGP.

Ph Ph Ph
H
O18 O18 O18
O NGP O O
OBs Ph
18
O H S N2 H
OAc
H (inversion) H H
H O OBs H OAc
OAc
Ph O18
H H
H
O AcO OAc
 18
PhOCO O18COPh
AcO
H H H
(/-) racemic mixture

23. What is the proof of NGP?

Let us take a trans isomer like this and perform acetolysis in presence of ethanol and we got
this product which clearly indicates the NGP mechanism.

OTs

OAc
Optically active (trans)
Optically active (trans)
CH3 CH3 EtO CH3
H
O O O
O NGP O EtOH O O OEt
OTs
OAc H SN2 
H (inversion) H H O CH3
H OTs H H

24. Predict the product of the following reaction-

OH
O
Cl OH O

 OH
H
H H 
H

trans isomer Cl

OH
O
Cl H
Cl H
 OH H H 
Cl
OH
trans isomer H
H OH O

OH O
Cl H
O
 OH
H
OH 

cis isomer Cl
 25. Predict the product of the following reaction-

H3C CH3
Ha S  
Hb SCH3 -CH3S-CO-SHa H3C
H3C
CH3 3-menthene (major)
O  -CH3S-CO-SHb
H CH3
H H H3C CH3

H3C
2-menthene

H
H
HC CH3
H3C CH3 -CH3S-CO-SH 3 

H CH3 H3C
H O 2-menthene
S
SCH3

26. Predict the product of the following reaction-

Ha -NMe2OHa Ph  Ph
Hb
CH3
Ph
N
H CH3 Ph  Ph
H -NMe2OHb
O

Ph
Hb
CH3 -NMe2OH
H Ph  Ph
N
H CH3
H
O