from "Master Organic Chemistry

"
Summary Sheet #7 - Identifying the Patterns in Carbonyl Reaction Mechanisms masterorganicchemistry.com
Version 1.1 Apr 2011, copyright 2010 James A. Ashenhurst
comments/corrections/suggestions? james@writechem.com

O Reactions of neutral NR2 NR2
HO R nucleophiles with
Grignard Reaction 12A P R X SN2 D
R–MgX alkyl halides R R R
R R R R

Reactions of HO RO
O anionic nucleophiles R X R OR R OH R CN SN2
HO CN
Cyanohydrin NaCN 12A P with alkyl halides CN
formation R R R R
O base O
O Enolate alkylation R X
Ketone or aldehyde HO H D SN2
NaBH4 (ketones or esters) R CH2R R R
reduction 12A P
or LiAlH4 R R R R R

O O O OH O
base HO H
Base-catalyzed aldol 12A 12E 12A P
D 12A P Reduction of esters LiAlH4
reaction R CH2R H R R R R OR R H
R

Addition of neutral O O
nucleophiles to acid RNH2 Grignard Reaction O HO R
12A 12E D + acid chloride, RMgX 12A 12E 12A P
halides or anhydrides R Cl R NHR
(e.g.amines, alcohols, water) ester, or anhydride R Cl R R

O O O O R
O acid N
Addition of anionic nucleophiles HO RO
12A 12E Imine formation RNH2 P 12A PT 12E D
to acid halides or anhydrides R Cl R OH R OR R NH2 R R R R
H2N
(e.g.RO , H2N , HO )

O O O O O acid O
base PT D
Claisen condensation D 12A 12E Fischer esterification ROH P 12A 12E
R CH2R R OR R R R OH R OR
R
O O
O R2CuLi O acid
1,4 addition of Gilman Amide hydrolysis H2O P 12A PT 12E D
14A P R NR2 R OH
reagent R R

R
O O O O O acid RO OR
base D
Formation of acetals ROH P 12A PT 12E 12A
Michael reaction D 14A P R R R R
R CH2R R R R
R

O O RO OR acid O
Hydrolysis of acetals H2O P 12E 12A PT 12E D
RNH2 14A PT R R R R
1,4 addition of R R
neutral nucleophiles
RHN
O O acid O
Acid catalyzed aldol P T 12A PT T 14E D
R CH2R H R R R
R

The Nine Mechanistic Components (with examples)

[1,2] addition [1,2] elimination SN2 Deprotonation Proton Transfer

O O O O O
O Nu O base Intramolecular acid-base reaction
12A O Nu 12E SN2 R H R D PT
R H3C R H2C R example:
X R X R X R Nu R
Cα X H
Nu Removal of a proton from substrate H
HO OR H2O OR

[1,4] addition [1,4] elimination Protonation R R R R
Keto-Enol Tautomerization
O O H O acid O
OH O O OH
14A Nu P
14E T H2C R H3C R
R R H
R R H3C R R
Nu H Addition of a proton to substrate
Nu X β