INTRAMOLECULAR ACYLOLYSIS OF AMIDE DERIVATIVES OF KEMPS TRIACID - STRAIN EFFECTS AND REACTION-RATES

Intramolecular acylolysis of comparable secondary and tertiary amide d erivatives of Kemp's triacid, 4, and its cis,trans isomer 5 has been e xamined. For both triacids, the tertiary amide derivatives undergo acy lolysis about 1000 times faster than the corresponding secondary amide . Also, amide derivatives of Kemp's triacid undergo acylolysis about 1 00 times faster than the corresponding amide derivatives of the cis,tr ans isomer. Thus, acylolysis rates spanning a range of nearly 10(6) ar e observed. It is proposed that the large rate difference between seco ndary and tertiary amides in these molecules results from greater pseu doallylic (pseudo-A(1,3)) strain associated with the tertiary amides. It also is proposed that the slower acylolysis rates observed with ami de derivatives of the cis,trans isomer of Kemp's triacid result from g reater 1,3-diaxial strain associated with acylolysis of these compound s. The data show that both the structure of the triacid and the struct ure of the amide have a direct effect on the acylolysis rate. Because previous studies only focused on the structure of the triacid, the pro posal that intramolecular acylolysis of amide derivatives of Kemp's tr iacid is a useful model system for studying enzyme catalysis (Menger, F. M.; Ladika, M. J. Am. Chem. Sec. 1988, 110, 6794. Menger, F. M, Bio chemistry 1992, 31, 5368) is reexamined.