Effect of cyclodextrin on the intramolecular catalysis of amide hydrolysis

ALEJANDRO M. GRANADOS; RITA H. DE ROSSI

JOURNAL OF ORGANIC CHEMISTRY

American Chemical Society

Año: 2001 vol. 66 p. 1548 - 1552

0022-3263

The hydrolysis reaction of phthalamic acids (HOOCArCONHR, R = p-NO2Ph 1a, Ph 1b, adamantyl 1c) and N-phenyl maleamic acid 2b was studied in the presence of hydroxypropyl-β-cyclodextrin (HPCD) in acid solution. The reactions of 1a and 1b were studied also in the presence of β-cyclodextrin (β-CD). All the compounds formed inclusion complexes with HPCD, and the association constant was determined from the change in absorption of the substrate when the host is added in the case of 1a (90 M-1) and 2b (49 M-1). For 1c (4 × 104 M-1) a competition method was used, and for 1b the association equilibrium constant was obtained from the kinetic data (37 M-1) because it is too reactive for the spectrophotometric method. Both cyclodextrins strongly inhibited the reactions, and analysis of the kinetic data for HPCD indicated that the reactions of complexed 1a, 1b, and 2b are at least 10-30 times slower than in the bulk solution whereas 1c reacts only 4.6 times slower when it is complexed. The inhibition is attributed to changes in the geometry of the substrate due to interaction of the carboxylic group and/or the amide with the OH at the rim of the cyclodextrin. The differences in the relative effect observed for 1c are attributed to the formation of a tighter complex with this substrate.