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.