Intramolecular Acylolysis of Amide Derivatives of Kemp's Triacid: Strain Effects and Reaction Rates

Article abstract of DOI:10.1021/jo00092a006

Intramolecular acylolysis of comparable secondary and tertiary amide derivatives of Kemp's triacid, 4, and its cis,trans isomer 5 has been examined.For both triacids, the tertiary amide derivatives undergo acylolysis about 1000 times faster than the corresponding secondary amide.Also, amide derivatives of Kemp's triacid undergo acylolysis about 100 times faster than the corresponding amide derivatives of the cis,trans isomer.Thus, acylolysis rates spanning a range of nearly 1E6 are observed.It is proposed that the large rate difference between secondary and tertiary amides in these molecules results from greater pseudoallylic (pseudo-A^1,3) strain associated with the tertiary amides.It also is proposed that the slower acylolysis rates observed with amide derivatives of the cis,trans isomer of Kemp's triacid result from greater 1,3-diaxial strain associated with acylolysis of these compounds.The data show that both the structure of the triacid and the structure of the amide have a direct effect on the acylolysis rate.Because previous studies only focused on the structure of the triacid, the proposal that intramolecular acylolysis of amide derivatives of Kemp's triacid is a useful model system for studying enzyme catalysis (Menger, F.M.; Ladika, M.J.Am.Chem.Soc. 1988, 110, 6794.Menger, F.M.Biochemistry 1992, 31, 5368) is reexamined.