from "Master Organic Chemistry"

masterorganicchemistry.com
Version 1.1 Apr 2011, copyright 2010 James A. Ashenhurst
comments/corrections/suggestions? james@writechem.com

Summary Sheet #7 - Identifying the Patterns in Carbonyl Reaction Mechanisms

O
Grignard Reaction

RMgX

Cyanohydrin
formation

NaCN

HO
R

O
R

NaBH4
or LiAlH4

O
CH2R H

HO

CN

HO

Base-catalyzed aldol
reaction

R
O

Ketone or aldehyde
reduction

base
R

12A

12A

12A

Reactions of neutral
nucleophiles with
alkyl halides
Reactions of
anionic nucleophiles
with alkyl halides

NR2
R
HO

SN2

OR

OH

CN

SN2

CN
O

Enolate alkylation
(ketones or esters)

RO

NR2
R

base

CH2R

SN2

R
O

OH

12A

Reduction of esters

LiAlH4

12A

12E

Grignard Reaction
+ acid chloride,
ester, or anhydride

RMgX

Imine formation

RNH2

HO

HO

OR

12A

12E

12A

12A

12E

12A

12A

PT

12E

12A

PT

12E

12A

PT

12E

12A

PT

12E

12A

12E

12A

PT

12E

12A

PT

14E

R
Addition of neutral
nucleophiles to acid
halides or anhydrides
(e.g.amines, alcohols, water)

O
R

HO
Cl

O
Claisen condensation

Addition of anionic nucleophiles

to acid halides or anhydrides
(e.g.RO , H2N , HO
)

RNH2
Cl

RO

OH

base
OR

H2N

CH2R R

NHR

O
R

OR

O
12A

NH2

12E

12A

14A

12E

Fischer esterification

ROH

Amide hydrolysis

H2O

R
O

acid

O
D

acid

Cl

OH

OR

R
O
1,4 addition of Gilman
reagent

R2CuLi
R

acid

NR2

OH

RO

OR

R
O
Michael reaction

base

CH2R

14A

Formation of acetals

ROH

Hydrolysis of acetals

H2O

acid

RO

OR

R
O
RNH2

1,4 addition of
neutral nucleophiles

O
R

14A

PT

RHN

O
Acid catalyzed aldol

O
CH2R

acid

R
O

acid
R

The Nine Mechanistic Components (with examples)

12A
C

Nu

12E

Nu

SN2
R

Nu

O
R

Nu

OH
R

Nu

14E

R
X

Deprotonation
O

R H
X

[1,4] elimination

Nu

Nu

[1,4] addition
14A

SN2

[1,2] elimination

[1,2] addition
O

H3C

T
R

H3C

base
R

H2C

OH
R

R
H

H2C

acid
R

Intramolecular acid-base reaction

example:

Protonation
O

PT

H
HO OR

Removal of a proton from substrate

Keto-Enol Tautomerization
H

Proton Transfer
O

H3C

Addition of a proton to substrate

H2O OR
R