Distorted amides as models for activated peptide N-C(O) Units. 3. Synthesis, hydrolytic profile, and molecular structure of 2,3,4,5-Tetrahydro-2-oxo-1,5-propanobenzazepine

A distorted amide (2,3,4,5-tetrahydro-2-oxo-1,5-propanobenzazepine (1d) was synthesized and its structure determined by X-ray diffraction. The amidic unit of 1d is compared with that found in undistorted p-bromo-N,2-dimethylacetanilide (3b) and more distorted 2,3,4,5-tetrahydro-2-oxo-1,5-ethanobenzazepine (1b) and 3,4-dihydro-2-oxo-1,4-propanoquinoline (1c). The progressive distortion manifests itself in a lenghtening of the N-C(O) bond, a slight shortening of the C=O bond, and a twisting about the N-C(O) unit with attendent rehybridization of the N from sp 2 to sp 3 and a slight pyramidalization of the (N)(C)C=O unit. Based on the solvent kinetic isotope effects, pH/rate profiles, and activation parameters, a unified mechanism for H 3 O + - and OH − -promoted hydrolysis of these anilides is proposed. The effect of varying [acetate] in catalyzing the hydrolysis of 1b and 1c in H 2 O and D 2 O as a funciton of pL was studied and analysed in terms of a specific-acid/general-base process involving acetate-promoted delivery of L 2 O on protonated amide