Synthesis Of3,5-Disubstituted-4,5-Dihydroisoxazoles Via1,3-Dipolar Cycloaddition

This paper focus on the synthesis of a series of novel4,5-dihydroisoxazoleheterocyclic compounds via1,3-dipolar cycloaddition reaction.In order to synthesize of3,5-disubstituted-4,5-dihydroisoxazoles, a three-stepsynthetic procedure was developed, which involved addition-elimination, chlorinationand1,3-dipolar cycloaddition. In the first two steps, aryl oximes were synthesizedfrom the reaction of aromatic aldehydes and hydroxylamine hydrochloride underalkaline solution, then ten different hydroximoyl chlorides were generated from aryloximes and N-Chlorosuccinimide (NCS), which included benzohydroximoyl chloride,4-methylbenzohydroximoyl chloride,4-methoxybenzohydroximoyl chloride,3,4-methylenedioxybenzohydroximoyl chloride,4-chlorobenzohydroximoyl chloride,3-chlorobenzohydroximoyl chloride,2-chlorobenzohydroximoyl chloride,4-nitrobenzohydroximoyl chloride,4-nitrobenzohydroximoyl chloride and3-trifluoromethylbenzohydroximoyl chloride.Finally, nineteen novel4,5-dihydroisoxazole derivatives have been synthesized via1,3-dipolar cycloaddition of nitrile oxides and N-vinyl-2-pyrrolidinone/vinyl pyridine.Nitrile oxides were generated “in situ” with triethylamine from hydroximoyl chlorides.All the novel4,5-dihydroisoxazole derivatives were characterized by IR,1H NMR,13C NMR and HRMS.According to the preliminary discussion of the1,3-dipolar cycloadditionregioselectivity, the factors for1,3-dipolar cycloaddition were determined. Optimizingeach step reaction was studied by single factor method, and then to find the bestreaction conditions. Under the optimal reaction conditions, the majority of1,3-dipolarcycloadditions proceeded smoothly to give the desired products with satisfied yields.