Post on 12-Jan-2016
Chapter 7Rearrangement Reactions
（重排反应）
What is Rearrangement Reactions? The term of “rearrangements” is used to describe
organic reactions which involve the migration of an H atom or of a larger molecular fragment.
Nucleophilic Rearrangements Electrophilic rearrangements Radical rearrangements
1. Nucleophilic Rearrangements
[1,2]-Rearrangements
C CCC
R(H)R(H)
++
1
1' 2'
1
1' 2'
NN CC
R(H)R(H)
+ +
1
1' 2'
1
1' 2'
(1) Wagner-Meerwein rearrangements
Wagner-Meerwein Rearrangements are [1,2]-rearrangements of H atoms or alkyl groups in carbenium ions that do not contain any heteroatoms attached to the valence-unsaturated center C-1 or to the valence-saturated center C-2.
C CCC
R(H)R(H)
++
1
1' 2'
1
1' 2'
H+CH3 C
CH3
CH3
CH2OHH2O
CH3 CCH3
CH3
CH2OH2
CH3 CCH3
CH3
CH2H+
Cl-
CH3 CCH3
CH2CH3
CH3C=CHCH3
CH3
CH3 CCH3
CH2CH3
Cl
Wagner-Meerwein rearrangements
Carbenium ions: 1 °→2 ° ， 1 °→3 ° 2 °→3 ° Reactions include Wagner-Meerwein
rearrangement step: 1. Electrophilic additions of alkenes 2. Nucleophilic substitutions (SN1) 3. E1 elimination 4. Friedel-Crafts alkylation reactions, etc
Carbocation Stability
CH3+ < CH3CH2
+ < (CH3)2CH+ < CH2=CH-CH2+ < C6H5CH2
+
Example: Friedel-Crafts Alkylation 1-Bromopropane isomerizes quantitatively to 2-
bromopropane under Friedel-Crafts conditions. The [1,2]-shift A→B involved in this reaction again is an H-atom shift.
Br
H
CH3
HH
H
CH3
HH
H
HBr
NO2
cat. AlCl3 in
AlBr4-
A B
AlBr4-
- AlBr3
++
Wagner-Meerwein rearrangement as part of an isomerizing E1 elimination
OH
H H
OH2 H
H
conc. H2SO4
_ H2O
_H+
+
+
+
Methyl shift
Example:
CH3 CCH3
CH3
CH2
CH3 CCH3
CH2CH3H+
H2OCH3 C
CH3
CH2CH3
OH
CH3
CH3
CH3
CH2NH2
HNO2
CH3
CH3
CH3
CH2NH2
HNO2
CH3 CCH3
CH2CH3
OH
MechanismMethyl shift
+
+
Example: Nucleophilic Substitution
CH2NH2CH2OH OH
HNO2+ + +
CH2NH2CH2
HNO2
CH2OH OH
+ +
++
Mechanism
Example: E1 and Nucleophilic Substitution
Wagner-Meerwein rearrangement as part of an HCl addition to a C=C double bond
+ +
+
Cl
Cl ClA B
C D
HCl
Alkyl shift
Ring expansion
An E1 elimination involving five Wagner-Meerwein rearrangements
Alkyl shift
Ring expansion
R OH R
R RH
N :
SOCl2pyridine
+
+
+CH3
CH3 CH3
CH3
OHOH
CH3
CH3
CH3
CH3
OH
CH3
CH3
CH3O
CH3
H
CH3
CH3 CH3
CH3
OH2OH
CH3
CH3
CH3O
CH3
H2SO4OH2
H+_
_
pinacol
pinacolone
+
+
CH3
CH3
CH3O
CH3
H
+..
(2) Pinacol Rearrangements Mechanism of the pinacol rearrangement of a
symmetrical glycol
1. Protonation of a hydroxyl group
2. Loss of water
Resonance-stablized carbocation
3. Methyl migration4. Deprotonation
R1
R2 R3
R4
OHOH
?????????
CH3 CH3
OHOH
PhPh
CH3
CH3
OHOH
Ph
Ph
• Which hydroxyl group is lost as water? or Which carbrnium ion forms first? • What is the inherent shifting tendency (migratory apptitude) of different substituent groups? or Which group migrates?• What is the influence of steric hindrance and other strain factors on the rearrangement? (the steric chemistry)• Are epoxides formed as intermediates in the pinacol rearrangement?• Do the reaction conditions (i.e. type of acid, concentration, solvent and temperature) influence the course of rearrangement?
Regioselectivity of the pinacol rearrangement of an unsymmetrical glycol
OH
Me
OH
Me
Ph
Ph
OH
Me
Me
Ph
Ph
Me
Me
O
Ph
Ph
H2SO4
Me
Me
OH
Ph
Ph
B C
D
A
+
+
Why?
OH
Et
OH
Et
Ph
Ph
OH
Et
Et
Ph
Ph
Et
Et
O
Ph
Ph
H2SO4
H+_
FE
+
Which carbenium ion forms first?
The stable cation formed superior
H+Ph2C
OHCH2OH
+Ph2C CH2
OH
H+Ph2CH CH
OH+Ph2CH CH
O
Ph2CH CH
OH
+
Which intermediate carbocation is more stable?
Which group migrates?
Phenyl group move first
PhHCOH
CHPhOH
H+PhHC CHPh
OH+
Ph2CH CHOH+
Ph2CH CHOH+
Ph2CH CHOH
+
Group moved as the following order:tertiary alkyl ＞ aryl ＞ H ＞ secondary alkyl＞ primary alkyl ＞ methyl
Solved problemExplain the following experimental facts ：
OH
R
R
OH
RR
O
R
O
R
CH2SO4
+
(A) (B) (C)
When R=CH3, （ B ） and （ C ） are formed ；When R=Ph, only （ C ） is formed.
+
+
- H
- H
:
:
+
+
+
+
+
+
R
R
OH (6)
C R
R
OH (3)
C R
R
OH (5)
C R
R
OH (2)
C R
R
OH2OH (4)
C R
R
OHOH2 (1)
(C)
(B)
(A)
+ +H
R
C R
O
O
R
R
OH OH
R
C R
When R=Me
When R=Ph
OH OH
Ph
Ph
OH OH2
Ph
Ph
OH
Ph
Ph
OH
Ph
Ph
O
Ph
Ph
OH OH
Ph
Ph
OH2 OH
Ph
Ph
Ph
Ph
OH
Ph
OH
Ph
Ph
O
Ph
- H2O
- H2O
H+
++
- H+
+
Phay A
Phay B
H+
+
+
- H++
C
B
The steric chemistry of
Pinacol Rearrangements
£«
£«
£«
Me
OH
Me
OH
Ph
Ph
Et
OH
Et
OH
Ph
Ph
Me
OMe
Ph
Ph
C2H5
OEt
Ph
Ph
H+
Me
OEt
Ph
Ph C2H5
OMe
Ph
Ph
and
NO
OH
OH
CH3
CH3
OH
CH3
OH
CH3
H+
H+
OH
OH
CH3
CH3
OH
CH3
OH
CH3
O
CH3
CH3
O
CH3
CH3
O
CH3
CH3H+
H+
+
The steric chemistry of
Pinacol Rearrangements ?
? Leaving group and shifting
group must be anti-coplanar
(3)Tiffeneau-Demjanov Rearrangements ----Semipinacol Rearrangements
R NH2 R N
H
H
N O R N N O
H
R N N O H
H
R N N O H
H
R N N O H R N N OH2 R N N
H+OH2
-H3O+
N O
OH2
H+
-H3O+
-H3O+
..
+..
+
..
..
:+
..
:+
.... ..
..
:..
:
+
:..
.. + ..
.. ......
:
Primary amine Nitrosonium ion
N-nitrosoamine
Protonated N-nitrosoamine
Diazonium ion
Reaction Mechanism
+R
R'
R'
R
OH
R'
R
HO
R
H
R
R H
R'
OH N2
R'
R
HO
R
N2
H+_
_
+
+
R'
R
HO
CH3
H
+..
Loss of nitrogen gas
Resonance-stablized carbocation
Alkyl migration
Deprotonation
Semipinacol Rearrangements
H+
OH N N OH HO OOH NH2
+
_
B
++
N2_
A
O OH NH2O
A
1) HCN or CH3NO2/NaOH
2) LiAlH4
3) NaNO2
HCl
Useful reaction for Ring expansion
More examples
1)
2)
CH3O
CH3
O O
OH
CH2NH2
NaNO2 , HCl
+ CH2N2
H+
OH
CH3
NH2
CH3O
CH3
CH3
O
CH3
CH3NaNO2
H+
OH
CH3
NH2
CH3
t-Bu
O
CH3
CH3
NaNO2
H+
+
The steric chemistry of
Pinacol Rearrangements
-..
OCH3
H O
CH3C6H5
C6H5CH3
OHH
C6H5CH3
OHH
OCH3
-HNO2
+
C6H5
CH3
OH
H
OCH3
+
+
+
OCH3
OCH3
H
H
OHNH2
CH3
N2C6H5 N2
The steric chemistry of
Pinacol Rearrangements
Summary
(1)Wagner-Meerwein rearrangements (2) Pinacol Rearrangements (3)Tiffeneau-Demjanov Rearrangements
----Semipinacol Rearrangements
Finish the following reactionsand write reasonable mechanisms
CCH2SO4
H+
p-CH3OC6H5
p-CH3OC6H5
OH
C6H5
C6H5
OH
ClOH
C(CH3)2(CH3)2CAgNO3
OH OH
H Cl1.
2.
3.
4.