Effect of Cyclodextrins on the Hydrolysis of Amides

Article abstract of DOI:10.1021/jo00059a030

The hydrolysis of p-nitrotrifluoroacetanilide (1), trifluoroacetanilide (2), m-nitrotrifluoroacetanilide (3), and p-nitroacetanilide (4) was studied in the presence of cyclodextrins.The reactions of 1 are catalyzed by α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) and also by hydroxypropyl)cyclodextrin (HPCD).The hydrolysis of 4 is catalyzed by β-CD.The reaction of 2 is inhibited by β-CD and so is the reaction of 3 by HPCD.Copounds 1 and 4 form two types of inclusion coplexes with β-CD, a 1:1 and a 1:2 substrate:cyclodextrin complex.Both types of complexesreact faster than the free substrate, and for 1 at pH = 7 all the catalysis is due to the reaction of the 1:2 complex since the 1:1 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 coplexing the substrate stabilize the transition state for water addition.