Synthesis and Mosquito Repellent Properties of 2,2-Dialkyl- and 2-Alkyl-4,4-dimethyl-N-acetyloxazolidines

Abstract

Nineteen novel N-acetyl-2,2-dialkyloxazolidines (2) and N-acetyl-2-alkyl-4,4-dimethyloxazolidines (3) were synthesized from commercially available carbonyl compounds and ethanolamine or 2-amino-2-methyl-I-propanol. Their bioactivity against laboratory-reared mosquitoes was compared in patch tests to known N-acetyl-2-alkyloxazolidines (1) and N,N-diethyl-m-toluamide (deet insect repellent). Isomeric composition measurements by ["ClNMR spectroscopy favoured the Z rotational isomer for samples of 2 (91-96% Z) and the E rotational isomer for samples of 3 (66-71% E), in agreement with molecular mechanics calculations on rotational isomers of model oxazolidines. Samples of 1 were previously shown to exist in solution mostly as the Z isomer (60-70% Z). Within the optimal molecular weight range for these experimental chemicals, the duration of repellency against Aedes aegypti (L.), Anopheles quadrimaculatus Say and Anopheles albimanus Wiedemann generally followed the order: 1 > 2 > deet > 3. Bioassay data are discussed in relation to the equilibrium populations of rotational isomers for substituted N-acetyloxazolidines.

Stability Studies of Oxazolidine-Based Compounds Using 1H NMR Spectroscopy

“…Oxazolidines 1 (Fig. 1) have been synthesized for a variety of applications, including bacteriocides, fungicides, herbicides,1 and mosquito repellents 2. Several members of this class have been applied as chiral derivatizing or resolving agents,3 and used as chiral auxiliaries to effect asymmetric inductions in a variety of reactions 4–6.…”

Insect repellents - past, present and future

“…evolved by random drift of selectively neutral mutations (Rutledge et al, 1997). Although effective topical mosquito repellents fall in a range of molecular weights of 150-250 (Taylor et al, 1996), vapor pressure is the only parameter significantly related to mosquito repellent activity (Davis, 1985). Partition coefficient, molecular weight, infrared absorption, viscosity, surface tension, molecular polarizability, and Hammett substituent constants have all failed to be correlated to repellent activity (Davis, 1985).…”