Level 1 – Case 10
Nucleophile Versus Base Catalysis
Key point: Catalysis
Cl
O
R 3 N
+
OPh
O
PhOH
Nucleophile Versus Base Catalysis
To distinguish between nucleophile and base catalysis is not always a simple exercise. The reaction of acid chlorides and alcohols to form esters, in the presence of
amines as catalysts, is a nice playground to examine how to distinguish between
d
both processes. This reaction has been exhaustively studied, but most of the work
has been done in protic solvents and the mechanisms proposed are based on these
reports. The currently accepted mechanism for these reactions suggests a nucleophile catalysis, where the amine attacks the carbonyl group forming a transient tetrahedral intermediate. On displacement of the leaving group, a quaternary acylf
ammonium salt is formed. This ammonium salt is then susceptible to attack by
alcohol, water, or other nucleophiles to form the product (Scheme 10.1). However,
there is no experimental evidence of the formation of the acylammonium salt.
Other proposed mechanisms for amine-catalyzed reactions of carbonyl compounds
involve acylium ion and ketene intermediates (the latter can only occur for acid
halides containing D-hydrogens), but the actual role of the catalyst is still uncertain.
R 1
R 2
Cl
O
R 3 N
R 1
R 2
Cl
O
NR 3
R 1
R 2
NR 3, Cl
O
R
1
R 2
OR
3
O
+ R
3
OH
R
3
OH
NR 3, Cl
Scheme 10.1
Determine the most probable type of catalysis for these esterification processes,
using the reaction of benzoyl chloride and phenol, in dichloromethane (DCM) and
in the presence of tertiary amines, as a model.