ИСТИНА

Recently a preparative approach to 3-aryl-4-nitroisoxasoles has been elaborated in our laboratory. This process is based on the heterocyclization reaction of aryl substituted vinylketones I with t-BuONO in a mixture of dioxane and water [1]. In this work 5-methyl-4-nitroisoxazoles II were used for the functionalization of position 5 of the isoxazole moiety. For this purpose 5-methylisoxazoles II were involved in the condensation reaction with dimethylacetal N,N-dimethylformamide to obtain a series of 4-nitro-5-enamines III. It is known that enamines III are characterized by a variety of synthetic applications because they can react with electrophilic and radical agents [2]. We found that the reaction of enamines III with t-BuONO in the presence of BF3∙OEt2 proceeds with the formation of previously unknown 4-nitroisoxazol-5-carbonitriles IV. Using this general synthetic approach a large scope of substances IV was obtained in moderate to high yields. 4-Nitroisoxazol-5-carbonitriles IV, as a new structural type of isoxazol derivatives, are of interest to study their synthetic utilities. For carbonitriles IV two novel paths for modification were found with 4- nitroisoxazol-5-carbonitrile Iva as an example. The reduction of the nitro group at position 4 of isoxazole ring leads to 4-aminoisoxazol-5-carbonitrile Va in a good yield (60%), while SNAr reactions of cyano group at position 5 with N- and S-nucleophiles provide a range of isoxazole derivatives VI in 30-94% yields.