Chapter 12 Molecular Rearrangements
I Classification of Rearrangement Reactions( )
II Nucleophilic Rearrangement ( )
1 Wagner-Meerwein rearrangement( )
2 Pinacolic Rearrangement ( )
3 α-ethandione Rearrangement ( )
4 Beckmann Rearrangement ( )
5 Baeyer-Villiger Rearrangement ( )
III Electrophilic Rearrangement ( )
1 favorskii Rearrangement 2 Stevens Rearrangement
3 Wittig Rearrangement 4 Fries Rearrangement
IV Radical Rearrangement
PRODUCER：张文勤
I Classification of Rearrangement Reactions
Molecular Rearrangements:it refers those
reactions in which the carbon skeleton or the
position of functional group changed,
C H 3 C H 2 C H = C H 2 H 3 P O 4 C H 3 C H = C H C H 3
C H 3 C
C H 3
C H 3
C H 2 O H
H +
H 2 O
C H 3 C = C H C H 3
C H 3
C H 2 N H 2
H N O 3
C H 2 N H 2
C H 2 O H C H 2 O H
H 2 O
H +
C H 3 C
C H 3
O H
C
C H 3
C H 3
O H
C H 3 C
C H 3
C H 3
C
O
C H 3
Usually the rearrangement was classified by the
electron property of the moving group,such as
Nucleophilic rearrangement,Electrophilic rearrangement,
Radical rearrangement,etc.
Nucleophilic rearrangement
C H 3 C H 2 C H 2 C H 2 O H H +
H 2 OC H 3 C H 2 C H 2 C H 2 O H 2
C H 3 C H 2 C H C H 2
H
C H 3 C H 2 C H + C H 3 H +
C H 3 C H = C H C H 3
Electrophilic rearrangement
P h C H 2 O C H 3 P h L i
C 6 H 6P h C H O C H 3 L i +
P h C H O - L i +
C H 3 H
2 OP h C H O H
C H 3
Radical rearrangement
C
C l
C l
C l
C H = C H 2 B rC
C l
C l
C l
C H C H 2 B r
CC l
C l
C H C H 2 B r
C l B r
2CC l
C l
C H C H 2 B r
C lB r
II Nucleophilic Rearrangement
1 Wagner-Meerwein rearrangement
( Carbon cation rearrangement )
H +
C H 3 C
C H 3
C H 3
C H 2 O H
H 2 O
C H 3 C
C H 3
C H 3
C H 2 O H 2
C H 3 C
C H 3
C H 3
C H 2
H +
C l -
C H 3 C
C H 3
C H 2 C H 3C H
3 C = C H C H 3
C H 3
C H 3 C
C H 3
C H 2 C H 3
C l
C l
C l -
C l
-
C l
O H H ++ +
C H 3 C
C H 3
C H 3
C H C H 3
B r
S N 1 C H
3 C
C H 3
C H 3
C H C H 3
C H 3 C
C H 3
C H C H 3
C H 3
P r o d u c t
C H 3 C
C H 3
C H 3
C H P h
S N 1C H
3 C
C H 3
C H 3
C H P h
B r
P r o d u c t
C H 3 C
C H 3
C H P h
C H 3
C H 3 O ＞ ＞ ＞C l C H 2 = C H
＞ R 3 C ＞ R 2 C H ＞ C H 3 ＞ H
Stable cation
Stable cation
C H 3 C
C H 3
C H 3
C H 2 O H
N 2
H N O 2
C H 3 C
C H 3
C H 3
C H 2
C H 3 C
C H 3
C H 2 C H 3
H +
H 2 OC H
3 C
C H 3
C H 2 C H 3
O H
C H 2 N H 2 N H 2 H N O
2
N 2
C H 2
+
+
H
+
H 2 O
H
+
O HC H
2
O H
C H 2
N 2
H N O 2
C H 2 N H 2
H +
H 2 O
H +
C H 2 + C H 2 O H
3 2 %
+
H 2 O
H
+
O H
5 8 %
H +
2 %
N H 2 H N O 2
N 2
+ + H +
H 2 O
H +
H 2 O C H
2 = C H C H 2 O H
2 Pinacolic Rearrangement
C H 3 C
C H 3
O H
C
C H 3
C H 3
O H
H +
H 2 OC H 3 C
C H 3
O H
C
C H 3
C H 3
O H 2+
C H 3 C
C H 3
O H
C
C H 3
C H 3
+
C H 3 C
C H 3
O H
C
C H 3
C H 3
+ H
+C H 3 C
C H 3
O
C
C H 3
C H 3
The stable cation formed superior
H +P h
2 C
O H
C H 2
O H
+P h 2 C C H 2O H
H +
P h 2 C H C H
O H+
P h 2 C H C H
O
Phenyl group move first
P h H C
O H
C H P h
O H
H +
P h H C C H P h
O H+
P h 2 C H C H
OH
+P h 2 C H C H
O H+
Phenyl with electron donor group move first
( p M e O C 6 H 4 ) 2 C
O H
C P h 2
O H
H +
( p M e O C 6 H 4 ) 2 C
P h
C P h
O
p M e O C 6 4 C
O
C P h 2
C 6 H 4 O M e p
72%
28%
Under HNO2,the amino alcohol rearranges
as that of pinacol H N O 2
H N O
2
N H
2
O H
C H
2
N H
2
O H O
C H O
3 α-Ethandione Rearrangement
P h C C P h
OO N a O H
E t O H
P h 2 C
C O O N a
O H
H 3 O +
P h 2 C
C O O H
O H
P h C C P h
OO O H -
P h C C
P h
O O H
O
-P h C C
P h
O HO
-
O
P h C C
P h
O H O -
O
O H -R C C ROO R C C
R
O O H
O
-R C C
R
O HO
-
O
R C C
R
O H O -
O
O H
-
C C
OO
C C
O O H
O
-
C
O HO
-
O C
O H O
-
O
C H 3
C C C H 3
OO
O H
-
H 2 O
C H 3 C C
C H 3
OO
C C C H 3
OO
C H 3 C C
C H 3
O
H 2 O
O H
-
C C C H 3
O
C H 3 C C
O
α-Ethandione with α- hydrogen will
proceed condensation
R O H
N a O R
P h C C P h
OO H
3 O
+
P h 2 C
C O O R
O -
P h 2 C
C O O R
O H
P h C C P h
OO
C H 3 C H O
-
H
P h C C H P h
O O -
H 3 O +
P h C C H P h
O O H
If NaOH was replaced by NaOMe or t-BuONa,
α-hydroxycarboxyester will be produced
Usually,ethyloxy anion acts as a reduction reagent.
4 Beckmann Rearrangement
C
R
R '
N
O H
H + C
R
R '
N
H O
C
R '
R
N
H
O
C
C H 3
P h
N
H
O
P C l 5
C
P h C H
3
N
O H
e t h y l e t h e r
The group opposite to hydroxy will shift
E t 2 O,
C
P h C
6 H 4 O C H 3
N
O H
P C l 5
- 1 0 ℃
- p
m p 1 4 7 ℃
C
C 6 H 4 O C H 3
P h
N
H
O
℃1 7 1m p
C
P h
C
6
H
4
O C H
3
N
H O
U V l i g h t
℃1 1 7m p
- p
- 1 0 ℃
C
C 6 H 4 O C H 3
P h
N
H
OP C l
5
E t 2 O,
m p 1 5 6 ℃
B r
N
P h
O 2 N
O H
P C l 5 H 2 O
B r
OO
2 N
N H P h C O O H
B r
O 2 N
P h N H 2
B r
N
P h
O 2 N
O H
P C l 5N H C O P h
B r
O 2 N
H 2 O P h C O O HN H 2
B r
O 2 N
E t 2 O
C
C H 3 C
N
H O
C 2 H 5
H
C H 2 C 2 H 5 H
2 S O 4
C H 3 C O N H
C
C 2 H 5
H
C H 2 C 2 H 5
The shift will keep the stereostructure of
chiral center
5 Baeyer-Villiger Rearrangement
C H 3 C P h
O
C F 3 C O 3 H C H 2 C l 2 C H 3 C O P h
O
C H 3 C O O E t
C F 3 C O 3 H
O O
O
C H 2 C l 2
C F 3 C O O H
O
C H 3 C P h
O H+
+
C H 3 C P h
O H
C F 3 C O O H
O
C H 3 C P h
O H
C F 3 C O O
O H
+
C H 3 C O P h
O H
+ C F 3 C O O H
H +
C H 3 C O P h
O
C H 3 C C H
O
P h
C H 3
* C H
3 C O C H
O
P h
C H 3C H C l 3
P h C O 3 H
C F 3 C O 3 H
C H 2 C l 2
C H 3 C O C ( C H 3 ) 3
O
C H 3 C C ( C H 3 ) 3
O
P h C C H 2 C H 3
O
P h O C O C H 2 C H 3
O
C H 2 C l 2
C F 3 C O 3 H
C F 3 C O 3 H
C H 2 C l 2
P h C
O
P h O C
O
Group moved as the following order:
tertiary alkyl＞ aryl＞ H＞ secondary alkyl
＞ primary alkyl＞ methyl
P h C
C H 3
C H 3
O O H H
+
C
C H 3
P h
O O H 23 C
+
H2O_ CC H 3O P hH
3 C +
+CC H 3O hH
3 C
H2O
C
C H 3
O P hH 3 C
O H 2+
+
C
C H 3
O P hH 3 C
O H H
+P h O H C H 3 C C H 3
O H+
C H 3 C C H 3
O
+ H +
The cumene hydroperoxide rearrangement is
quite resemble the Baeyer-Villiger Rearrangement
Important industrial reaction for
manufacturing phenol and acetone
C H 3 C H = C H 2 a n h y d r o u s A l C l 3 P h C H ( C H 3 ) 2
P h C H ( C H 3 ) 2 O 2 N a 2 C O 3 / H 2 O
1 0 0 ℃
P h C
C H 3
C H 3
O O H H
+
P h O H C H 3 C O C H 3
III Electrophilic Rearrangement
Electrophilic rearrangement is not so common
as nucleophilic rearrangement
P h C
P h
P h
C H 2 C l
N aP h C
P h
P h
C H 2
-
N a +
P h C
P h
C H 2 P h
N a +
R O H
P h 2 C H C H 2 P h
P h C
P h
C H 2
The transition state is:
C C R
C l
O
K O H C C O H
R
O
1 Favorskii Rearrangement
N a O E t( C H
3 ) 2 C C C H 3
B r
O
( C H 3 ) 2 C C O E t
C H 3
O
E t O H
E t O H P h 2 C C H 2 C O E t
O
P h 2 C C C H 3
B r
O
N a O E t
C
OC l ①
②
N a O H / H 2 O
H 3 O +
C
O
C O O H
Mechanism of Favorskii Rearrangement
C
CC
C lH
O
R O
-
R O H
C
CC
C l
O
C l
-
C
CC
O
R O
-C
CC
R O O -
C
CC
R O O
R O H C
CC
R O O
H
For asymmetric cycloprapanone,the
stable anion form dominantly
O
P h
R O
-
P h
O
-R O
P h C H C H 2 C O O R
s t a b l e c a r b o n a n i o n
P h
O
-R O
P h C H
C O O R
C H 2
r e l a t i v e u n s t a b l e c a r b o n a n i o n
O
P h
P h C H 2 C H 2 C O O R
R O
-
P h C H 2 C C H 2
O
C l
P h C H C C H 3
C l
O R O H
Different α- chloroketone form same
rearrangement product:
M e
C O C H 3
C l
H K O H
M e
H
O
H O
-
M e
H
M e
C O O H
M e
H
C H 2 -
O
O H H +
K O H
M e
C O C H 3
C l
H
H O
-
M e
H
O
H +
M e
H
C H 2
-
O
O H
M e
H
M e
C O O H
Intramolecular SN2 attack(structure
maintaining):
2 Stevens Rearrangement
P h C O C H 2
N
C H 2 P h
H 3 C C H
3
H O - P h C O C H
N
C H 2 P h
H 3 C C H
3
P h C O C H
N
H 3 C C H
3
C H 2 P h
r e a r r a n g e m e n t
H 2 O
r e a r r a n g e m e n tP h C O C H
N
C H P h
H 3 C C H
3
C H 3
H O -P h C O C H 2 N C H P h
H 3 C C H
3
C H 3
* *
P h C O C H
N
H 3 C C H
3
C H P h
C H 3
*
Structure maintaining
The sulfonium cation does the same
H O -P h C O C H 2 S C H 2 P h
C H 3
r e a r r a n g e m e n tP h C O C H
S
C H 2 P h
C H 3
P h C O C H
C H
C H 2 P h
S
C H 2
N + ( C H 3 ) 2
C H 3
N a N H 2
N H 3
C H 2
N + ( C H 3 ) 2
C H 2
C H 2
N ( C H 3 ) 2
C H 2H C H 2 N ( C H 3 ) 2
C H 3
Sommelet Rearrangement
H 2 O
N a O HC H
2 S
+
C H 3
C H 3
C H 2 S
+
C H 3
C H 2
C H 2
S C H 3C H
2
H
C H 2
S C H 3C H
2
3 Wittig Rearrangement
P h C H 2
O
C H 3 P h L i
H +
P h C H
O
C H 3
P h C H
O
C H 3 H
+
P h C H
O H
C H 3
P h C H
O H
C H 2 P h
P h L i
P h C H 2 O C H 2 P h
H 3 O +②
①
C H O C H
3
①
② H 3 O
+
P h L i
C
O H
C H 3
C H 2 = C H C H 2
O
C H 2 = C H C H 2
N a N H 2
l i q N H 3
C H 2 = C H C H O H
C H 2 = C H C H 2
4 Fries Rearrangement
O C
O
C H
3
C H
3
A l C l
3
2 5 ℃
1 6 5 ℃
O C
O
C H 3
A l C L 3
h e a t
O H
C O C H 3
O H
C O C H 3
O H
C O C H
3
C H
3
O H
C O C H
3
C H
3
8 0 - 8 5 %
9 5 %
IV Radical Rearrangement
P h C
C H 3
C H 3
C H 2 C H O
( t C 4 H 9 O ) 2P h C
C H 3
C H 3
C H 2 C O C O
P h C
C H 3
C H 3
C H 2
H a b s t r a c t i o n
r e a r r a n g e m e n t
P h C
C H 3
C H 3
H 3
C
C H 3
C H 3
C H 2 P h
H a b s t r a c t i o n H CC H 3
C H 3
C H 2 P h
E t C
C H 3
C H 3
C H 2 C O
( t C 4 H 9 O ) 2
E t C
C H 3
C H 3
C H 2 C H O
E t C
C H 3
C H 3
C H 2 E t C
C H 3
C H 3
C H 2 C H 3
CO
P h 3 C O
C OP h
P h P h 2 C O P h P h 2 C O P h
P h 2 C O P h
( C H 3 ) 3 C O C H 3 C H 3 C O C H 3
Usually the aryl,alkenyl and acetoxy can shift
H 3 C C
C H 3
O A c
C H = C H 2
P r C OH
3 C C
C H 3
O A c
C H C H 2 C O P r
H a b s t r a c t i o nH
3 C C
C H 3
O A c
C H C H 2 C O P rH 3 C C
C H 3
O A c
C H C H 2 C O P r
H
2 0 % m o v e m e n t
C
C l
C l
C l
C H = C H 2 B r C
C l
C l
C l
C H C H 2 B r
CC l
C l
C H C H 2 B r
C l B r
2 CC l
C l
C H C H 2 B r
C lB r