Effect of cyclodextrins on the hydrolysis of amides

ALEJANDRO M. GRANADOS; RITA H. DE ROSSI

JOURNAL OF ORGANIC CHEMISTRY

AMER CHEMICAL SOC

Lugar: Washington; Año: 1993 vol. 58 p. 1771 - 1777

0022-3263

The hydrolysis of p-nitrotrifluoroacetanilide (11, trifluoroacetanilide (21, m-nitrotrifluoroacetanilide (31, and p-nitroacetanilide (4) was studied in the presence of cyclodextrins. The reactions of 1 are catalyzed by a-cyclodextrin (a-CD) and 8-cyclodextrin (8-CD) and also by (hydroxypropy1)cydodextrin (HPCD). The hydrolysis of 4 is catalyzed by 8-CD. The reaction of 2 is inhibited by 8-CD and so is the reaction of 3 by HPCD. Compounds 1 and 4 form two types of inclusion complexes with 8-CD, a 1:l and a 1:2 substrakcyclodextrin complex. Both types of complexes react faster than the free substrate, and for I at pH = 7 all the catalysis is due to the reaction of the 1:2 complex since the 111 complex reacts at about the same rate as the free substrate. The results are explained in terms of two mechanisms: one which involves the acylation of CD by the amides and another which predominates at neutral pH where the two cyclodextrins complexing the substrate stabilize the transition state for water addition.