Section 19.14 The Claisen Condensation 811After nucleophilic attack, the Claisen condensation and the aldol addition differ. In
the Claisen condensation, the negatively charged oxygen reforms the carbon–oxygen
bond and expels the group. In the aldol addition, the negatively charged oxy-
gen obtains a proton from the solvent.
The difference between the last step of the Claisen condensation and the last step of
the aldol addition arises from the difference between esters and aldehydes or ketones.
With esters, the carbon to which the negatively charged oxygen is bonded is also bond-
ed to a group that can be expelled. With aldehydes or ketones, the carbon to which the
negatively charged oxygen is bonded is not bonded to a group that can be expelled.
Thus, the Claisen condensation is a substitution reaction, whereas the aldol addition is
an addition reaction.
Expulsion of the alkoxide ion is reversible because the alkoxide ion can readily re-
form the tetrahedral intermediate by reacting with the ester. The condensation
reaction can be driven to completion, however, if a proton is removed from the
ester. Removing a proton prevents the reverse reaction from occurring, because the
negatively charged alkoxide ion will not react with the negatively charged ester
anion. It is easy to remove a proton from the ester because its central
is flanked by two carbonyl groups, making its much more acidic than the
a-hydrogensof the ester starting material.
a-hydrogenb-keto a-carbonb-ketob-ketob-ketoH 2 Oformation of a bond
by expulsion of RO−Claisen condensation:O ORO RRCH 2 C CHCORO ORRCH 2 CCHCOR−protonation of O−aldol additionO ORRCH 2 CH CHCHOH ORRCH 2 CHCHCH−+RO− +HO−p -OR
OO OO O
CH 3 O CH 3 CH 2 COCH 3Omechanism for the Claisen condensationCH 3 CHCOCH 3 CH 3 CHCOCH 3
H CH 3 O CH 3CH 3 CH 2 C CHCOCH 3CH 3CH 3 CH 2 C CHCOCH 3 CH 3 O−+−−+ CH 3 OH−
OO− OCH 3 ORRCH 2 C CHCOCH 3 CHCOCH 3 CH 3 OH
O ORCH 3 O−RCH 2 C C− COCH 3O ORRCH 2 C +
+
-keto ester -keto ester anion