Conformational effect on reactivty

1. LOVELY PROFESSIONAL
UNIVERSITY
TOPIC:- EFFECT OF CONFORMATION ON REACTIVITY
COURSE CODE:-CHE 541
SUBMITTED TO:-DR.NITIN TONDON
DEPTT.:- SCHOOL OF PHYSICAL SCIENCES AND
CHEMICAL ENGINERRING
SUBMITTED BY:-Madan kumar
Course:-M.sc(HONS.)chem.
Reg. No:-11614536
Roll No:-A14 1

2. INTRODUCTION
Relation between conformation and
reactivity and stability of acyclic compound
was first introduced by BARTON in
1950.According to which there is profound
effect of conformation on chemical reactivity
because the stereoelectronic and steric factor
are among the essential condition for
reaction. In the upcoming slides we discuss
the effect of conformation on reactivity with
examples.
2

3. ACYCLIC COMPOUND
3
E2 REACTIONS:-E2 reactions are stereospecific and most of
these are anti elimination. In anti elimination the five atoms
involved must be in same plane and the eliminating groups
must be trans to each other, the conformation is called
antipreplanar this is stereoelectronic requirement of anti
elemination.
EXAMPLE:-2-Bromo butane can give either cis- or trans-2-
butene

4. H3C
C
H
C
CH3
H
trans-2-butene
C
C
H
Br
CH3
H
H
H3C
2-Bromobutane
4
C
C
H
Br
CH3
H
H
H3C
2-Bromobutane
H3C
C
H
C
H
CH3
cis-2-butene
(Major)

5. 5
EXAMPLE:-Debromination of 2,3-dibromobutane with a metal such as Zn.
C
C
Br
Br
CH3
H
H
H3C
meso-2,3-dibromobutane
H3C
C
H
C
H
CH3
cis-2-butene
C
C
Br
Br
CH3
H
H
H3C
meso-2,3-dibromobutane
H3C
C
H
C
CH3
H
trans-2-butene
racemic mixture

6. CYCLIC COMPOUND
The effect of conformation on reactivity has been
studied mostly in the case of cyclohexanes because the
ring system is mostly occurs in natural products such as
steroids, terpenoids. Environments of axial and
equatorial group are different, hence the reactivity of
a given group depend on the conformation i.e.,
weather the group is axial or equatorial. Generally, but
not always, the equatorial substituents are more
reactive than the corresponding axial substituent.
6

7. a. Substitution reaction
7
• SN2 reactions take place more readily with axial
substituent than with equatorial .For example
the SN2 reaction of thiophenoxide ion with 4-t-
butylcyclohexylbromide having an axial bromine
takes place about 60 times faster than as
compared to the equatorial isomer because the
attack of the thiophenoxide ion on the equatorial
isomer is hindered by Beta axial hydrogens.
-
H
H
H
Me3C
H
Br
H
SPh
H
H
Br
H
Me3C
SPh

8. SN1 OTs
H
H
Me3C
H H
Me3C
H
H
H
H
OTs
H
Me3C
Slower
+
H
Me3C
H
H +
Faster
•Proceeds through
formation of carbocation
which relives the steric
strain of the axial isomer
due to 1,3 diaxial
interaction.
•SN1 reaction is sterically
assisted for an axial
substituent, such type of
steric strain not produce in
equatorial substituent.
•For example the
acetolysis of cis-4-t-
butylcyclohexyl tosylate
with an axial tosylate
group, is about 3.4 times
faster than that of trans
isomer.
8

9. ESTERFICAION
AND
HYDROLYSIS
Me Me
H
H
OCOMe
MeOC
O
H H
Cholestanyl
acetate (equqtorial ester)
Epicholestanyl
aceate (axial ester)
Equatorial and axial conformational isomer usually react at
different rate due to 1,3 -diaxial interaction. In the axial isomer
esterfication and hydrolysis occur less readily as compare to
equatorial conformation. For example , cholestanyl acetate having
acetate group placed on the equatorial reacts more readily than the
epicholastenyl having acetyl group placed on axial position.
9

10. ELIMNATION REACTION
• As we have already noted that the steroelectronic
requirement of an E2 reaction is that the eliminating group
should be antiperiplanar. In cyclohexane this relationship
exists when the substituent on the two adjacent carbon are
in axial position.
• In neomenthyl both the axial and equatorial eliminating
groups are at axial position thus it undergoes readily to
elimination and give the products.
• In menthyl chloride eliminating group is at equatorial.
consequently methyl chloride reacts slowly as compared to
neomenthyl chloride.
• Similarly, the cis isomer of 4-ter-butylcyclohexyl tosylate
undergo elimination in the presence of sodium ethoxide in
ethanol 100 times faster as compared to its trans isomer
this is because of the position of tosyl group.
10

11. 11
+
H
H
H
Cl
Cl
H
H
Cl
EtONa
25% 75%
100%
EtONa
Neomenthyl chloride
Menthyl chloride
three substiuents are
all euatorial is the
more stable chair
conformation
Conformation
of high energy
OTs
H
H
H
CMe3
H
TsO
H
H
CMe3
H
trans-isomer
undergoes slower elemination
cis-isomer
undergoes faster elemination

12. MOLECULAR REARRANGMENT
• Example of pinacol-pinacolone rearrangement
of 1,2-dimethyl-1,2 cyclohexanediol.
• The cis isomer of this diol on treatment with
acid undergoes a methyl shift to give 2,2-
dimethylcyclohexanone.
• The trans isomer undergoes ring contraction
to give cyclopentane derivative.
12

13. 13
CH3
CH3
CH3
OH
CH3
OH
Me
OH
CH3
OH
O
CH3
CH3
CH3
H+
H+
OH
+
+
CH3
C
O
CH3
OH

14. NEIBGHOURING GROUP
PARTICIPATION
• In neighbouring group participation, the group
participating as a neighbouring group must be
in a position to attack from the just opposite
side to leaving group.
• Acetolysis of trans-2-iodo cyclohexyl brosylate
which undergoes 2.7*10^6 times faster
acetolysis than the cis-isomer in which iodo
group cannot attack from the backside.
14

15. 15
..
+
I
..
I
OBs
I
I
BsO
..
-OBs
AcOH
OAc
cis isomer
undergoes very slow acetolysis
trans isomer
undergoes very fast acetolysis

16. OXIDATION
• Reaction having no steric requirement also display rate
differences between reaction of axial and equatorial
isomers.
• Oxidation of both cis and trans isomer of 4-tert-
butylcylohexyl with chromic acid gives the same
ketone.
• In the preferred conformation the cis isomer has an
axial which is removed in the oxidation to allow relief
from van der waals strain(1,3-diaxial interaction with
beta hydrogen), thus the reaction is three times faster
than that of trans isomer.
16

17. 17
OH
Me3C Me3C
Me3C
OH
Me3C
O
O
Slower
Oxidation
Faster
Oxidation
trans
isomer
cis
isomer

18. THANKS!
18