The Study Of Benzo[c]Isothiazole-2,2-Dioxide Derivatives By1,3-Dipolar Cycloaddition

The derivatives of benzo[c]isothiazole-2,2-dioxide is a kind of compounds with extensive biological activity. It is widely used as a central nervous system depressant, antihypertensive drugs, central nervous system stimulant, mothproof agents, wood preservatives, anti-progesterone hormone active agent, controlling undesired vegetation and so on. So the research of synthesis methods and biological activity of such compounds has become one of the hot spots. In this paper, a new type of benzo[c]isothiazole-2,2-dioxide-3-spiro-3’-pyrrolidine derivatives are synthesisd with azomethine yelide by1,3-dipolar cycloaddition reaction. And we find a new method for the synthesis of these compounds, So far, to the best of our knowledge, there have been no reports on the synthetic of benzo[c]isothiazole-2,2-dioxide-3-spiro-3’-pyrrolidine derivatives with azomethine yelide. The results of our studies, which led to an unprecedented synthesis of benzo[c]isothiazole-2,2-dioxide-3-spiro-3’-pyrrolidine derivatives, are presented herein.This paper is divided into three parts:(1) The compounds of1-methyl-1,3-dihydro-benzo[c]isothiazole-2,2-dioxide was synthesized from o-Chlorobenzyl chloride by sulfonylation reaction, methyl iodide methylation reaction and cyclization reaction. In this part, the optimum reaction condition of cyclization reaction was researched, namely with sodium amide as alkali, ammonia as the inert solvent, the optimum reaction time is6hours, total yield reached74%.(2)1-Methyl-3-methylene-1,3-dihydro-benzo[c]isothia zole2,2-dioxide and its derivatives was synthesized from1-methyl-1,3-dihydro-benzo[c]iso thiazole-2,2-dioxide with a series of aldehydes by Knoevenagel condensation reaction. In this part, the condensation reaction conditions was also researched, for aliphatic aldehydes and methyl glyoxylate:potassium carbonate as alkali, DMF as the solvent; for aromatic aldehydes: potassium hydroxide as alkali, anhydrous ethanol as the solvent.(3) we synthesized benzo[c]isothiazole-2,2-dioxide-3-spiro-3’-Pyrrolidinespirocompoundswith azomethine yelide (Benzyl-methoxymethyl-trimethylsilanylmethyl-amine) by1,3-dipolar cycloaddition reaction. Nine benzo[c]isothiazole-2,2-dioxide-3-spiro-3’-Pyrrolidine derivatives were synthesized in this paper, and the structure of all the synthesized compounds were characterized by1H NMR, and MS spectrum.