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Copyright 2019 O O
O M O M NR 2 M
R–OH/ H 2O/ NaBH 4 LiAlH 4
James Ashenhurst R–MgX RO R R–NH 2 M–CN
masterorganicchemistry.com OR R R R–OM M–OH
β−keto ester amine alcohol/ water/ Sodium Lithium aluminum
james@masterorganicchemistry.com
Grignard Ester enolate Ketone enolate Enamine Cyanide
enolate (primary amine) alkoxide hydroxide borohydride hydride

O OH OH O OH O OH NR 2 O O R OH RO OR HO OH OH OH
N
A R H R R R OR R R R R RO R R CN R H R H R H R H
R H H H H
Aldehyde 2° alcohol Aldol Reaction Aldol Reaction R Imine Cyanohydrin Acetal Hydrate 1° alcohol 1° alcohol
Knoevenagel (aldimine) Requires acid (usu. thermodynaically
heating under basic conditions will lead to Condensation catalysis to form disfavored, except for
elimination of OH - Aldol condensation electron poor aldehydes)
also note that reaction can be reversible If aldehyde is enolizable,
under basic conditions : Retro-aldol reaction hydroxide can form enolate.

O OH O O O O O NR 2 O OH O O O O OH OH
B R Cl R R R OR R R R R RO R R NHR R CN R OR R OH R H R H
R H H
Acyl chloride 3° alcohol β−keto ester O R Amide Acid nitrile Ester Carboxylic acid 1° alcohol 1° alcohol
(Schotten-Bauman
reaction)

O O O O O NR 2 O O O O O O OH
O O OH
R OR R R R R RO R R NHR R CN R OR R OH Borderline R H
C R O R' R
R
R H
Anhydride 3° alcohol O R Amide Acid nitrile Ester Carboxylic Acid 1° alcohol

O OH OH O OH O OH NR 2 O O R OH RO OR HO OH OH OH
N
D R R' R R R OR R R R R RO OR R CN R R' R R R H R H
R' R' R' R R R' R' R' R'
Ketone 3° alcohol Aldol Reaction Aldol Reaction R R Imine Cyanohydrin Acetal Hydrate 2° alcohol 2° alcohol
(ketimine) Requires acid see above: even less
Note: best when ketones are favored than with aldehydes
catalysis
identical or when only one can due to sterics
enolize (to avoid scrambling)

O O O O O O NR 2 O OH O O O O
Varies with Varies with conditions: 1,2
E R conditions: 1,2 R OR R R R R RO R R R R R adduct is kinetic product, 1,4
adduct is adduct is thermodynamic.
kinetic pdt. RHN NC RO RO
α, β unsaturated Michael Reaction Michael Reaction
ketone (enone)
O R Note: in both cases, very prone to Note: Easily
the reverse reaction (elimination) reversible
O OH O O O O O O O OH
F Borderline Borderline NR NR H
R OR R R R OR R R R NHR R OR' R OH R
R H
Ester 3° alcohol β−keto ester: 1,3 diketone: Amide Transesterification Saponification 1° alcohol
Claisen Condensation Claisen Condensation Can be done under basic (basic conditions)
or acidic conditions. Can also hydrolyze
O with aqueous acid OH
O O
G R OH NR R H
Deprotonation Deprotonation Deprotonation NR Deprotonation R NHR H
R OR' ––– NR
Carboxylic acid 1° alcohol
Usually requires Fischer esterification
dehydration (requires acid, heat)
agent (e.g. DCC)

O O
1° and 2° amides: 1° and 2° amides: Borderline reaction: H H
H R NH 2 Deprotonation deprotonation deprotonation NR NR NR NR requires strong acid, R OH NR NH 2
3°amides: NR 3°amides: NR alcohol as solvent, heat R

Amide Amide Hydrolysis Amine

Requires strong
conc. acid, heat
O O NR 2 O O
Mix of addition R
I R X /deprotonation R OR R R R RO R R NHR R CN R OR R OH NR R H

R
Alkyl halide Enolate Enolate Stork enamine Amine Williamson requires Alkane
Alkylation Alkylation reaction Ether Synthesis basic
note: capable of caution! product conditions
alkylating is a good nucleophile; requires basic
a second time multiple alkylations conditions
usually result