A CONVENIENT METHOD FOR THE PREPARATION OF 2-ARYL(HETERYL)-5-CHLOROMETHYL-1,3,4-OXADIASOLES

The 1,3,4-oxadiazole molecule is of considerable interest due to a wide range of biological and pharmacological activities and has been generally recognized as a privileged structure in drug chemistry. The development of convenient methods for the production of substituted 1,3,4-oxadiazoles is an important area of research. Particularly interesting are derivatives of 1,3,4-oxadiazoles containing of the reactive chloromethyl group, which allows their further chemical modification. This paper is devoted to the development of a convenient preparative method of obtaining 2-aryl/heteryl-5-chloromethyl-1,3,4-oxadiazoles. A scheme is proposed in which aromatic and heterocyclic carboxylic acids are commercially available starting materials. The method is based on the preparation of carboxylic acid hydrazides, their subsequent acylation and cyclization of synthesized intermediates under the action of phosphorus trichloroxide (V). The advantages of the method are the high yields of the targeted 1,3,4-oxadiazoles and the absence of the need to purify the intermediate compounds, which greatly simplifies the procedure, shortens the required time, saves the necessary reagents. The method is suitable for the preparation of both a wide range of 5-aryl-2-chloromethyl-1,3,4-oxadiazoles and some derivatives with heterocyclic substituents, in particular 5-thienyl (furyl)-2-chloromethyl-1,3,4- oxadiazoles. The structure of all the compounds obtained was confirmed by 1H NMR spectra and their composition by elemental analysis. The results of these studies can be applied in synthetic practice, and the obtained compounds containing the reactive chloromethyl group are promising building blocks for their further chemical modification in order to obtain biologically active derivatives, which may find use as drugs, insecticides