An investigation of the rotational isomers of N-acetyl-2,2-dimethyloxazolidine and related compounds by nuclear magnetic resonance spectroscopy and molecular mechanics

Abstract

The 15 2,2-dimethyloxazolidines described here were found to exist in solution predominantly as a single rotational isomer, unlike N-acetyloxazolidine (1), N-acetyl-2-methyloxazolidine (2), N-acetyl-2-(n-octyl)oxazolidine (3), and other known 2-substituted N-acyloxazolidines. Using 13C NMR spectroscopy, activation energies for interconversion of the E (minor) and Z (major) rotational isomers of 1–3 were determined from coalescence temperature measurements in pyridine-d5. A sample of N-acetyl-2,2-dimethyloxazolidine (4) was isolated for comparison. The rotational isomer of 4 was found by two-dimensional nuclear Overhauser effect spectroscopy (NOESY) to possess the Z (or trans) stereochemistry. Molecular mechanics (MMX) calculations on the E and Z isomers of 1–4 helped to account for these findings. The conformation of the energy-minimized structures resembled a C-5 envelope. Samples of N-aroyl-2,2-dimethyloxazolidines (5a–5n) were isolated and the rotational isomers were assigned the Z stereochemistry by NOESY and 13C NMR experiments. Most of these 2,2-dimethyloxazolidines were ineffective in a bioassay for mosquito repellent activity. Keywords: N-acyloxazolidines, N-aroyloxazolidines, NMR spectroscopy, rotational isomerism, molecular mechanics.