Lecture Notes Chemistry 342-2008 Mukund P.

Sibi
Lecture 29
Reactions at the Alpha-Carbon of Carbonyl Compounds
"
O H2
C C Both the ! and !' hydrogens are acidic. However, the " and #
H3C C CH3 hydrogens are not acidic.
H2
!' ! #

The C-H bond on the alpha carbon of carbonyl compounds (aldehydes, ketones, acids,
and acid derivatives) have modest acidity (pKa 17-25) depending on the functional group.
The alpha C-H bond can be deprotonated to create a carbon nucleophile. The carbonyl
compounds exit in an equilibrium with their enol isomers (alkene alcohols). The
equilibrium is generally towards the carbonyl compound. The ketone and its enol
counterpart are tautomers, compounds with different structures. They are not resonance
structures.

H
O rapid O
H C H H H
C C C C
H H H
H H H H
Ketone Enol
C-H on H
!-carbon O O
H
C rapid C
H H

aldehyde Hydrogen Enol

Aldehydes and ketones with no C-H bonds on the !-carbon

O O O
O CH3
C C C
H H3C C
C H
H3C
CH3

In general, carbonyl compounds exist in their keto form. For example, at equilibrium, the
enol tautomer of acetone is present in about 0.0000001%. In comparison to aldehydes
and ketones, carboxylic acids and its derivatives have even lower amounts of enol form.

The keto-enol tautomerism of carbonyl compounds is catalyzed by both acids and bases.
The mechanism for acid and base catalysis of keto-enol tautomerism is shown here. In
the acid catalyzed process, protonation of the carbonyl oxygen allows provides the
oxonium ion. The acidity of the alpha proton is increased by the positive charge on the
carbonyl carbon. Deprotonation by the base (just like E2 elimination) provides the enol.
Lecture Notes Chemistry 342-2008 Mukund P. Sibi
Lecture 29

H+ H H H
O O O Base O
C H C H C H C + BH+

Ketone Enol

The base catalyzed enoalization also provides an enol from a carbonyl compound. In this
case the base deprotonates the alpha proton that is rendered acidic by the carbonyl group.
Water than protonates the oxygen to provide the enol and the base catalyst.

O
H H H
O OH O O O
H
C C C C + HO
C C C

Ketone Enol

Alpha-Substitution Reactions: Reactivity of Enols:

The enol tautomer of carbonyl compounds is nucleophilic on the α-carbon. Thus

Aldehydes and ketones undergo halogenation on the α-carbon under acid catalysis. One
can do chorination, bromination, and iodination. Mechanistic studies suggest that follows
second order kinetics (substrate and acid catalyst) and the reaction rate is independent of
halogen concentration. This means that halogenation occurs in a fast step which is after
the rate determining step.

O O
C H C Br
Br2
C C
H H H3CCO2H H H

H H Base
O O O O
H Br Br C Br C Br
C
C H+ C
C
H
C C
H H H H H H H

Further evidence for the mechanism comes from deuteration experiments. When one
treats a ketone or an aldehyde with D3O+, all the C-H bonds are replaced by C-D.
Lecture Notes Chemistry 342-2008 Mukund P. Sibi
Lecture 29
O O
H D
C
C D3O+ C
C
H H D D

The α-halo compounds are useful for preparing α,β-unsaturated carbonyl compounds.
The halo compounds undergo dehydrohalogenation using a base.

O O O

Br2 Br Pyridine
H+ heat

Carboxylic acids do not form enols readily (the alpha C-H is not very acidic). However,
they undergo halogenation with bromine and phosphorous tribromide. The reaction is
called Hell-Volhard-Zelinski reaction.

Br
OH OH
C 1. Br2, PBr3 C
O 2. H2O O

OH PBr3 Br Br Br2
C C C
O O OH

Br Br
Br OH
C H2O C
O O