They can exist in acids:

They can exist in bases:

Keto vs. Enol Form:

 O OH

O OH OH
H3 C H3 C
CH3 H3 C +
CH3 CH2
H3 C H H3 C H
CH3

O OH

H3 C H H2 C CH3

H
O O
O O

H3C CH3 H3C CH3

OH O

How Acidic is An Alpha Hydrogen?

H3C
CH3
H H

H2C CH3

H2C H

H2 C O CH3

O
CH3
H2 C N
CH3
H
 O O

H3 C CH CH3

O O

H3 C CH H

O O

H3 C CH O CH3

O O

H3 C O CH O CH3

H
Halogenation of Aldehydes/Ketones in Acid
O

H H+
H/R
Cl2
H3C CH3

Halogenation of Aldehydes/Ketones in Base

O

H OH-
H/R
excess Br2
H3C CH3
The Haloform Reaction for methyl ketones ONLY!!!!

O
OH-

R CH3 excess X2
Enolate Formation and Bases
O
H3C H + Base

H H

Base pKa of HB+ % enolate

Alkylation of Aldehydes/Ketones
O

LDA
THF

O
1. NaOH
or NaOEt
or KOtBu

2. CH3Br

Will Alkylation work with aldehydes?

Enolate Preference
O

CH3
LDA
Alkylating the Less Substituted Carbon
O
CH3 CH3
H3C N NH2

mild acid
Using Enamines/Imines to Alkylate
O

trace acid
+

N
H

N
H CH3Br HCl
trace acid H2O

O
O

N
H Cl CH3 HCl
trace acid H2O
Aldol Condensation
O OH-
2 R H2O
H

Dehydration of the Aldol Product

Aldol Additions

O OH-

2 H3C H2O
H

O OH-

2 H2O
H3 C CH3
Crossed Aldol
O O OH-
CH3 +
H H2O
H CH3
How do you prevent a crossed Aldol?

Intramolecular Aldol
O
OH-
H3C
CH3 H2O
O
 O
OH-
H3C
CH3
H2O
O
Chem 320 Chapter 18 Partial Notes part 2

Q: How CAN you alkylate an aldehyde and avoid Aldol

condensation?

O
H3C
H

,-unsaturated aldehydes and ketones

Direct vs. Conjugate Addition to ,-unsaturated aldehydes and
ketones

O
1. Nuc

2. H3O+
H3C CH3

O
1. Nuc
H3C CH3 2. H3O+
O & N Nucleophiles (and others)

O
1. Ca(OH)2

H3 C CH3 2. H2O

O
1. CH3NH2

H3C CH3 2. H2O

O
1. CN-

H3C CH3 2. HCl

O
HBr
H3C CH3
 O

H 1. NaBH4

2. EtOH

1. NaBH4

2. EtOH

Grignard Reagents as the Nucleophile

O
1. RMgX
H3C CH3 2. H+, H2O
However.
O

CH2 1. C6H5MgBr

2. H3O+

OrganoLithiums as the Nucleophile

O
1. RLi
H3C CH3 2. HCl

Gilman Reagents as the Nucleophile

O
1. (CH3)2CuLi

H3C CH3 2. EtOH

,-dialkylation
O

1. (CH3CH2CH2)2CuLi, THF

2. CH3I
Michael Addition.
O
O
KOH
+ H2C H2O
CH3

Robinson Ring Annulation

Propose a Synthesis of these Compounds Using a Robinson Ring Annulation
O

H3 C

CH3

H3 C