Epoxide formation

OH OH

X X

X
O
O O

X X

O
O
No epoxide

Only diaxial conformation forms epoxide

X
 Epoxides

O O

X +
+
O
X

TS
This TS is same for ring opening or formation of epoxide

Since the opening is possible only in diaxial substituted cylohexanes,

the ring opening products also has to be diaxial
 But But
Q. 1. Ph3P, X2
CH2Cl2

2. H2O
~95% OH
O X

Whereas
But But
1. Ph3P, X2
CH2Cl2

2. H2O
~95% X
O HO

X = Cl, Br, I
 O But O

But
X X

OH •Twist boat, too high

O
in energy to form.

•Barrier to reaction
Bu t But that matters not the
X final product
X

X
But X
•Ring opening of
cyclohexene oxides
But always leads directly to
O O diaxial products
 Epoxides

H O H

H
Y OH
Y
O
H H
Y
H H
H Y O OH

H Y H Y
(Product formed)
 Elimination Reactions

E2

E1

E2 E1

(CH3)2CHCH2Br + HO-
 Substitution vs Elimination

Temperature, Concentration, Solvent (EtOH vs H2O)

E2 eliminations have anti-periplanar transition states
Two conformations with H and X coplanar

In E2 eliminations, the new  bond is formed by overlap of

the C-H  bond with the C-X * antibonding orbital
E2 eliminations have anti-periplanar transition states

Me groups gauche Me groups anti-

(syn-clinal) periplanar
more hindered Less hindered

Reaction is stereoselective
 Br H3C C6H5
Only one proton for removal OH
C6H5
C6H5
(faster)
CH3 C6H5 H
H Ph Br
Br Br Ph
Ph CH3
CH3
H
Ph H H Ph
CH3
Ph H H

Br H3C C6H5
C6H5 OH
C6H5
(slower)
CH3 H C6H5
Br
H Ph Br Me
Br Me Ph
Ph
H
Me H Ph
Ph
Ph H
H H
 Br C6H5 CO2H
C6H5 CO2H
C6H5 CO2H
C5H5N
H COC6H5 H
H COC6H5 COC6H5

Whereas Br
H
C6H5 C6H5
HO2C C5H5N

H COC6H5 H COC6H5

Br
H C6H5 H
C6H5 C5H5N

H COC6H5
H COC6H5

CO2H
Predict the product of following reaction

OMe

HO2C H
HNO2

HO

NH2
 CH3 CH3
CH3
Q.
NaOEt
+
(faster
Cl reaction)

1:3
OEt
H H
Me

Me

Cl Cl

CH3 CH3
Cl Me

NaOEt Me
Cl
(250 times H
Cl slower) Slow
OEt
Q. Br
Br
I

(faster)

Br
Br
I

(slower)

Br
Br
fast fast
Br

Br

I I
Br
Br Br fast
Br
I
I
slow
I
SN2
 Reactions of 2-bromo-4-phenylcyclohexanols with base and silver oxide
C6H5 Br O

O
OH
C6H5 C6H5

Ag2O H
or OH- Ag2O Ag2O
or OH- Or OH-
OH
OH H
Stable not
C6H5 suitable for -HBr
OH
C6H5 Br C6H5
Br
Br
Ag2O
C6H5 Br OH
CHO
Ag2O induces –Br-
C6H5
C6H5
Br
OH-
O

C6H5
OH
 CHO

:OH
..
OH NaNO2, HCl NaNO2, HCl N2
N2

OH
OH
NH 2 NH 2

OH

OH
H
.. NH 2 NH 2
OH NaNO2, HCl :OH
NaNO2, HCl
N2

N2
O
O
Q. Br
Br
I

(faster)

Br
Br
I

(slower)

Br
Br
fast fast
Br

Br

I I
Br
Br Br fast
Br
I
I
slow
I
 SN1 solvolysis
Cl OEt solvolysis
solvolysis
+ OEt Cl
EtOH EtOH
1-chlorobut-2-ene
3-chlorobut-1-ene

Cl Allylic rearrangements

In presence of high concentration of EtO- in EtOH

R
EtO
X
EtO R SN2'

Tends to occur when “R” is bulky enough to reduce markedly

the rate of direct SN2 displacement on C.
 SN2: Inversion of configuaration
SN1: ideally Racemization

Retention of configuaration : SNi ( substitution nucleophilic internal)

Me Me
S OCl 2
OH Cl + SO 2 + HCl
Ph Ph

H H

Rate = K [ROH] [ SOCl2] S N2

Then how the configuration is retained?

Me O
Me

OH
SOCl2 O S Cl + HCl
Ph Ph

H H

Me O Me O Me Me
Slow
OSCl OS Cl Cl Cl
Ph Ph Ph Ph
H H H H
Cl attacks from the
same side with
Ion pair retention configuration
Problem:

Me Me

OH SOCl2
Ph Cl
Ph
Py H
H
Inversion

Me O
Me

OH
SOCl2 O S Cl +
Ph Ph
N Cl
H H H
N

Me O Me
SN2
OSCl Cl
Cl Ph Ph
H H
 /
Examples of SNi reaction
Cl
SOCl2
H3CCH CHCH2OH H3C C CH CH2
Ether
H
(only)
H SOCl2
H3C C CH CH2 H3C CH C CH2Cl
Ether H
OH (only)

Mechanism

H3C
CH2
H3CCH CHCH2 O S Cl
..
.Cl. O

..
O
S

H3C CH CH2
CH + SO2

Cl
 Neighboring Group Participation (Anchimeric asssitance)

Hydrolysis of EtS–CH2CH2 – Cl is 104 times faster than that of EtO–CH2CH2–Cl. Why?

.. slow fast ..
EtS EtS
EtS
Cl Cl OH

..
OH2

Reaction of CH3COOH with

MeO reacts four times slower than
OSO2Ar OSO2Ar
Reaction of ROH with
Me
O
OSO2Ar OSO2Ar
Me
OMe
reacts 400 times faster than
 Neighboring Group Participation : Retention of configuration
Et2
Et2(HO)C C
NaOH HO
Cl OH Retention
Me Me
H H
Et2
C
-
OH -O
OH
Et2 Et2 Me
-
C C OH H
Inversion 1 Inversion 2
O -
OH
Cl O
Me Me
H
H
 Neighboring group participation

Q. H HNO2
O S S H
O
CO2H O CO2H
OH H2N

H
R
HO O O H
O S H H
O
OH C
N2 O
O
Q. Which one will undergo SN1 solvolysis faster? Exaplain?

CH3

H3C C CH2Cl H3C C C Cl

I
H H H2
II

phenonium ion

δ
H H + Cl
H
H H H
Cl H
H3C Cl H3C H
TS H3C H
Sol OH

Solvolysis products
Q. Which compound solvolyses faster in HOAc containing NaOAc
(I or II)?

The product is the same from either I or II. What is the structure
of the product?

S S

H Cl

Cl H
II
I

OAc
Q. Which compound solvolyses faster in HOAc? (I or II). Give the
structure of the product from I.
OTs OTs

I II


OTs
OAc

HOAc
I

III

Participation of the π electrons of the double bond gives the ion

III, which would be stabilized by delocalization of the positive
charge.
I undergoes 1011 times greater rate than II
Q.
O
X X X X
O

Relative rate 1.0 0.014 0.14 4.85 x 10 4

Explain
Transannular participation of ether oxygen

O
O O

..
I II III

III is more favorable than either I or II

Unfavorable polar effect of the C-O bond
 Quinuclidine
Q. Which one reacts with MeI more rapidly ?

..N
..N
I II