Chapter 7 Rearrangement 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

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.

Wagner-Meerwein rearrangements Carbocation Stability CH3+ < CH3CH2+ (CH3)2CH+ CH2=CH-CH2+ C6H5CH2+ 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

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.

Wagner-Meerwein rearrangement as part of an isomerizing E1 elimination Example: Wagner-Meerwein rearrangement as part of an isomerizing E1 elimination Methyl shift

Example: Nucleophilic Substitution HNO2 Methyl shift Mechanism HNO2 C H 3 + C H C C H 3 2 C H 3 + H O C H C C H C H 2 3 2 3 + C H H 3

Example: E1 and Nucleophilic Substitution Mechanism

Wagner-Meerwein rearrangement as part of an HCl addition to a C=C double bond Alkyl shift Ring expansion

An E1 elimination involving five Wagner-Meerwein rearrangements Alkyl shift Ring expansion

(2) Pinacol Rearrangements Mechanism of the pinacol rearrangement of a symmetrical glycol 1. Protonation of a hydroxyl group 2. Loss of water 3. Methyl migration 4. Deprotonation Resonance-stablized carbocation

• Which hydroxyl group is lost as water • 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? ?????????

Which carbenium ion forms first? Regioselectivity of the pinacol rearrangement of an unsymmetrical glycol Why?

The stable cation formed superior + Which intermediate carbocation is more stable?

Which group migrates? Phenyl group move first + P h C H C H 2 O H Phenyl group move first Group moved as the following order: tertiary alkyl＞aryl＞H＞secondary alkyl ＞primary alkyl＞methyl

Solved problem Explain the following experimental facts： When R=CH3,（B）and（C）are formed； When R=Ph, only（C）is formed.

When R=Me

When R=Ph

The steric chemistry of Pinacol Rearrangements

The steric chemistry of Pinacol Rearrangements ? Leaving group and shifting group must be anti-coplanar

(3)Tiffeneau-Demjanov Rearrangements ----Semipinacol Rearrangements Primary amine Nitrosonium ion Protonated N-nitrosoamine Diazonium ion N-nitrosoamine

Reaction Mechanism Loss of nitrogen gas Alkyl migration Deprotonation Resonance-stablized carbocation

Semipinacol Rearrangements Useful reaction for Ring expansion

More examples

The steric chemistry of Pinacol Rearrangements

The steric chemistry of Pinacol Rearrangements

Summary (1)Wagner-Meerwein rearrangements (2) Pinacol Rearrangements (3)Tiffeneau-Demjanov Rearrangements ----Semipinacol Rearrangements

Finish the following reactions and write reasonable mechanisms