A ring-fission/C–C bond cleavage reaction with an N-alkyl-N-methyl-N-[(5-phenyl-1,2,4-oxadiazol-3-yl)methyl]amine

Abstract

The reaction of N-(3,4-dichlorophenethyl)-N-methylamine (1) with 3-chloromethyl-5-phenyl-1,2,4-oxadiazole (2) was investigated. Employment of an equimolar amount of 1 and 2 in the presence of potassium carbonate led to the expected tertiary amine 3 (N-[(3,4-dichlorophenyl)ethyl]-N-methyl-N-[(5-phenyl-1,2,4-oxadiazol-3-yl)methyl]amine), whereas an excess of 1 and prolonged reaction time resulted in ring fission of the oxadiazole system in 3 and finally in the formation of N′-benzoyl-N-[(3,4-dichlorophenyl)ethyl]-N-methylguanidine (4) and N,N′-bis[(3,4-dichlorophenyl)ethyl]-N,N′-dimethylmethanediamine (5). The structures of products 3–5 were determined by means of ¹H and ¹³C NMR-spectroscopy, mass spectrometry and IR-spectroscopy, for 3 (as picrate) and 4 also X-ray structure analysis was employed. A possible mechanism of the reaction pathway leading to compounds 4 and 5 is proposed.

Introduction

In the course of a project directed to the synthesis of potential new sigma-receptor-ligands^1a–e of type A, we were interested in compounds containing an oxadiazole ring as heterocyclic partial structure R (Scheme 1). The synthesis of compound A usually was carried out via alkylation of N-(3,4-dichlorophenethyl)-N-methylamine (1) with appropriate chloro- or bromoalkyl substituted hetarenes² (Scheme 1). Thus, we investigated the reaction of 1 with 3-chloromethyl-5-phenyl-1,2,4-oxadiazole (2) in order to obtain the corresponding oxadiazole derivative of type A (n=1, R=5-phenyl-1,2,4-oxadiazol-3-yl).