Hydrolysis and carbonyl-oxygen exchange in tertiary amides. Estimation of the free energy changes for breakdown and conformational changes of tetrahedral intermediates

Abstract

Second order rate constants were measured at several temperatures for the basic hydrolysis and for concurrent carbonyl-oxygen exchange with solvent for N-benzyl-N-methylformamide- 18 O, N-benzyl-N-methyltrideutéroacetamide- 18 O, and N-benzyl-N-methyl-α,α-dideuteropropionamide- 18 O. Carbonyl-oxygen exchange with solvent is rationalized by invoking a conformational change in the tetrahedral intermediate. Energy barriers for these conformational changes are estimated to be of the order of 5.6, 8.0, 8.2 kcal/mol respectively for the above amides.