The Study On 1,3-Dipolar Cycloadditions Between Derivatives Of Benzisothiazole And Ntrile Oxide

Derivatives of benzisothiazole have a variety of biological activity and pharmaco logical activity are of very important organic skeleton structures, so they are widely used as the central nervous system sedative, central nervous system stimulant, progesterone withdrawal resistance activator and antihypertensive drugs. Inspired by the spirooxindoles, we get a new type of isoxazole heterocyclic compound via reation between derivatives of benzisothiazole with nitrile oxide. Currently, the synthetic methods for such compound have not been reported. Therefore, the establishment of the method for building with similar isoxazole ring structure provides a new methodology basis.In this paper, we accomplished the following works:(1) 2-bromoaniline as raw material,1-methyl-1,3-dihydro-benzo thiazole-2,2-oxides was produced with reactions of methane sulfonyl chloride acylation, methyl iodide methylation reaction, molecular inner ring in order. (2) 3-methylene-l-methyl-1,3-dihydro-benzo[c]isothiazole 2,2-diox ide and so on was get via Knoevenagel condensation by condensating 1-methyl-1,3-dih ydro-benzothiazole-2,2-oxides with acetalde in the base of the catalyst. (3) a series of novel isoxazole heterocyclic compound have been synthesized via 1,3-dipolar cycl oiddition of nitrile oxide and 3-methylene-l-methyl-1,3-dihydro-benzo[c]isothiazole 2,2-dioxide and so on. Using NMR and high resolution mass spectrometry analysis method on the synthetic product structure characterization, found that the structure of the product and we expect there is a big difference, through the analysis of reaction mechanism, puts forward the trend of oxazoline aromaticity make SO2 benzothiazole of benzothiazole is easy to leave, to the synthesis of such compounds to provide the basis for later.According to the preliminary discussion of the 1,3-dipolar cycloaddition regioseselectivity,this factor for 1,3-dipolar cycloaddition were determined.Optimizing each step reaction was studied by single factor method, and then to find the best reac tion condition:NaHCO3 as bases,reaction temperature is 50℃, the mole ratio of derivatives of benzisothiazole and dipolar is 1:6, the reaction time is 12 h.