Synthesis Of New [1,5] Benzothiazepine Derivatives Containing 2-Phenyl-1,2,3-triazole And Study Of Its Cycloaddition Reaction

The 1,5-benzothiazepine as a special functional framework, has been widely used in synthetic drugs. 1,5-Benzothiazepine and its derivatives have potential biological activity of broad-spectrum, are often used as tranquilizer and medicines for cardiovascular disease. Scientists pay great attention to their synthetic method and structure-activity relationship. The biological and pharmacological properties of the 12,3-triazole containing compounds are also well known to be highly active. Its derivatives exhibit insecticidal, antibiotic, anticancer and other activities. In previous literatures, the research of 4-heterocycle substituted 1,5-benzothiazepines is seldom. Therefore, we obtained a series of novel compounds by introduction of 2-phenyl-1,2,3-triazole ring into 1,5-benzothiazepine. Recently much research work has been indicated the additional triazole orβ-lactam ring annulated to the 1,5-benzothiazepine can provide more satisfying metabolic stability and novel pharmacological properties. According to the design principle of drugs, we combinedβ-lactam and 1,2,4-triazole which have biological activities with 1,5-benzothiazepines by [2+2]cycloaddition reaction and 1,3-dipolar cycloaddition reaction respectively, and a series of novel tricyclic condenst 1,5-benzothiazepines derivatives were synthesized. Otherwise, we obtained a series of new dihydro pyrazole derivatives which containing 1,2,3-triazole through 1,3-dipolar cycloaddition reaction.The thesis includes two major parts:The first part is about literature review:In this part, The important synthetic methods, physiological and pharmacological activities of l,5-benzothiazepine derivatives that have been studied were explicated systematically; also introduced a more comprehensive properties and synthetic methods of 1,2,3-triazole; and briefly elucidated [2+2]cycloaddition reaction and 1,3-dipolar cycloaddition reaction.The second part is about experimental content. Major works as follows: 1. Synthesis and characterization of 1,4-diaryl-3-ethoxycarbonyl-5-(2-phenyl-1,2,3-triazole -4-yl)-4,5-dihydropyrazole derivatives.α,β-Unsaturatedketon synthesized from 2-phenyl-4-acetyl-1,2,3–triazole and a series of p-substituted benzaldehydes, which reacted with (aryl-hydrazino) chloromenthylenecarboxylates under refluxing to give dihydro pyrazole derivatives.2. Synthesis and characterization of 2-aryl-4-(2-phenyl-1,2,3-triazole-4-yl)-2,3-dihydro-1,5 -benzothiazepines 1,5-Benzothiazepines containing 2-phenyl-1,2,3-triazole were synthesized fromα,β-unsaturated ketones and 2-aminothiophenol.3. Synthesis and characterization ofα-chloro or phenoxy substitutedβ-lactam annulated with 1,5- -benzothiazepine derivatives underwent [2+2] cycloaddition reaction A new series ofα-chloro or phenoxy substitute-β-lactam-1,5-benzothiazepine derivatives containing 1,2,3-triazole were synthesized from 1,5-benzothiazepines andα-chloro or phenoxy substitute-β-lactam via [2+2] cycloaddition reaction.4. Synthesis and characterization of 1,2,4-triazolo-1,5-benzothiazepine derivatives underwent 1,3-dipolar cycloaddition reaction A new series of 1,5-benzothiazepine derivatives simultaneously containing 1,2,3-triazole and 1,2,4-triazole were synthesized from 1,5-benzothiazepines and benzoyl hydrazone via 1,3-dipolar cycloaddition reaction.Above all, the structures of the new compounds were confirmed by elememtal analysis, IR, 1H NMR and MS spectral data, and their spectral property were also discussed.