and therefore readily accepts the pair of electrons left behind when the substrate loses
Decarboxylation forms an enamine. Hydrolysis of the enamine produces the decar-
boxylated product (acetone) and regenerates the enzyme (Section 18.6).
PROBLEM 43When the enzymatic decarboxylation of acetoacetate is carried out in the acetone
that is formed contains^18 O.What does this tell you about the mechanism of the reaction?H 218 O,CO 2.
Summary 829Tutorial:
Common terms:
reactions at the -carbonaSummary
A hydrogen bonded to an of an aldehyde, ketone,
ester, or N,N-disubstituted amide is sufficiently acidic to be re-
moved by a strong base because the base that is formed when
the proton is removed is stabilized by delocalization of its neg-
ative change onto an oxygen. A carbon acidis a compound
with a relatively acidic hydrogen bonded to an hybridized
carbon. Aldehydes and ketones are more
acidic than esters and
are even more acidic.
Keto–enol interconversioncan be catalyzed by acids or
by bases. Generally, the keto tautomeris more stable.
When an takes place under acidic
conditions, an enol reacts with an electrophile; when the
reaction takes place under basic conditions, an enolate ion
reacts with an electrophile. Whether C or O reacts with the
electrophile depends on the electrophile and the reaction
conditions.
Aldehydes and ketones react with or Under
acidic conditions, a halogen replaces one of the
of the carbonyl compound; under basic conditions, halogens
replace all the The HVZreaction brominates
the of a carboxylic acid. When the is
halogenated, the reacts with nucleophiles.
LDA is used to form an enolate in reactions that require
the carbonyl compound to be completely converted to eno-
late before it reacts with an electrophile. If the electrophile is
an alkyl halide, the enolate is alkylated. The less substituted
a-carbona-carbon a-positiona-hydrogens.a-hydrogensBr 2 , Cl 2 , I 2 :A-substitution reactionB-keto esters 1 pKa' 1121 pKa' 252 .B-Diketones 1 pKa' 921 pKa ' 16 – 202sp^3A-carbon is alkylated when the reaction is under kinetic
control; the more substituted is alkylated when the
reaction is under thermodynamic control. Aldehydes and
ketones can be alkylated or acylated via an enamine
intermediate. Enolates of
esters, and nitriles undergo Michael reactionswith
carbonyl compounds. Michael reactions
form 1,5-dicarbonyl compounds.
In an aldol addition, the enolate of an aldehyde or a ke-
tone reacts with the carbonyl carbon of a second molecule
of aldehyde or ketone, forming a or a
The new bond forms between the
of one molecule and the carbon that formerly was
the carbonyl carbon of the other molecule. The product of
an aldol addition can be dehydrated to give an aldol con-
densationproduct. In a Claisen condensation, the enolate
of an ester reacts with a second molecule of ester, eliminat-
ing an group to form a ester. A Dieckmann
condensationis an intramolecular Claisen condensation.
A Robinson annulation is a ring-forming reaction in
which a Michael reaction and an intramolecular aldol addi-
tion occur sequentially.
Carboxylic acids with a carbonyl group at the 3-position
decarboxylatewhen they are heated. Carboxylic acids can
be prepared by a malonic ester synthesis; the of
the diester is alkylated and the malonic ester
undergoes acid-catalyzed hydrolysis and decarboxylation;a-substituteda-carbon- OR b-keto
a-carbonb-hydroxyketone. C¬Cb-hydroxyaldehydea,b-unsaturatedb-ketob-diketones,b-diesters,b-ketoa-carbona-carbonOEENHNH 2 OC
CH 3CH 2OCO−C
CH 3CH 2OCH 2 Oa protonated imine+
+EENHNH 2 OC
CH 3
CH 3
C
CH 3+ CH^3
ENHC + CO 2
CH 3CH 2an enamine+−H 3 O+acetoacetate
decarboxylase acetoacetateacetone