Distorted amides as models for activated peptide N-C=O units. 2. The synthesis, hydrolytic profile, and molecular structure of 3,4-dihydro-2-oxo-1,4-propanoquinoline

Abstract

A distorted anilide (3,4-dihydro-2-oxo-1,4-propanoquinoline (3)) has been synthesized, its structure determined by X-ray diffraction, and its hydrolysis profile from pH 0–13 investigated. The amide unit in 3 is distorted in that the N lone pair is twisted 35° and tilted 15° out of optimum conjugation with the C=O II system. Due to this distortion, 3 hydrolyses rapidly in H 2 O at 25 °C. The pH/rate constant profile exhibits domains consistent with OH − attack on 3[Formula: see text] and H 2 O attack on a protonated form of 3[Formula: see text]; pK a (3-H + ) = 0.56). The kinetic pK a is most consistent with an N-protonated form. It is also shown that this mechanism of hydrolysis is common to the series of bridged anilides consisting of 3, 3,4-dihydro-2-oxo-1,4-ethanoquinoline (1), and 2,3,4,5-tetrahydro-2-oxo-1,5-ethanobenzazepine (2). Keywords: distorted amide, hydrolysis, X-ray structure.