Organic Chemistry

If nitro groups are put on the benzene ring, the ortho-carboxyl substituent acts as an

intramolecular nucleophilic catalystinstead of an intramolecular general-base cata-

lyst. It increases the rate of the hydrolysis reaction by converting the ester into an an-

hydride, and an anhydride is more rapidly hydrolyzed than an ester.

PROBLEM 12 SOLVED

What causes the mode of catalysis to change from general base to nucleophilic in the hy-

drolysis of an ortho-carboxyl-substituted phenyl acetate?

SOLUTION The ortho-carboxyl substituent is in position to form a tetrahedral intermedi-

ate. If the carboxyl group in the tetrahedral intermediate is a better leaving group than the

phenoxy group, the carboxyl group will be eliminated preferentially from the intermediate.

This will reform the starting material, which will be hydrolyzed by a general-base-catalyzed

mechanism (path A). However, if the phenoxy group is a better leaving group than the car-

boxyl group, the phenoxy group will be eliminated, thereby forming the anhydride, and the

reaction will have occurred by a mechanism involving nucleophilic catalysis (path B).

PROBLEM 13

Why do the nitro groups change the relative leaving tendencies of the carboxyl and phenyl

groups in the tetrahedral intermediate in Problem 12?

PROBLEM 14

Whether the ortho-carboxyl substituent acts as an intramolecular general-base catalyst or

as an intramolecular nucleophilic catalyst can be determined by carrying out the hydroly-

sis of aspirin with water and determining whether is incorporated into

ortho-carboxyl-substituted phenol. Explain the results that would be obtained with the two

types of catalysis.

(^18) O-labeled (^18) O
1014 CHAPTER 24 Catalysis
H 2 O
CH 3 CO
OO
C
NO 2
O 2 N
NO 2
O 2 N
NO 2
O 2 N
NO 2
O O 2 N
−
−O
OC
CH 3 C O− HO
CH 3 C −OOC
O
O
O
C
C
CH 3
O
O
O
− +
an ester an anhydride
O
H 2 O H 2 O
CH 3 CO
−OO
C
A
B
A B
tetrahedral intermediate
O
−O
OC
O− HO
−O
CH 3 C
−OOC
CH 3 C
O
O
O
C
C
CH 3
O
O
O

• NO 2
  O 2 N
  NO 2
  O 2 N
  NO 2
  O 2 N
  NO 2
  O 2 N