Miscellaneous Zhuo Synthesis Of 3-methylene-4-aryl-aryl-2,3-dihydro-1,5-benzothiazepine And β- Lactam Derivatives

The1,5-Benzothiazepines are a kind of seven-membered ring heterocyclic compounds which possess many pharmacology activities and biological activities. They are often used as tranquilizer and medicines for cardiovascular disease. For many years, the structure, synthetic methods and biological activities attracted the extensive attention both at home and abroad. The ring addition reaction of the C=N double bond has caused the chemists’ great interest, because this functional group carries on one of the main reactive position of chemical modification and derivatization. Therefore, we can synthesize and develop a series of the new1,5-Benzothiazepine and1,5-Benzodiazepine derivatives; It has been shown that the pharmacological activities of parent molecules will apparently be improved with introduction of1,2,4-triazole ring into some active molecules:such as fluconazole, itraconazole and so on. In previous literatures, the research of3-heterocyclic substituted1,5-benzothiazepines is seldom. Therefore, we expect to realize reinforcement of many physiological activities by means of combining1,2,4-triazole with1,5-benzothiazepine. And introduces a new chiral carbon atom at the same time.But the outcome was out of our anticipation. What we got is3-arylidene-4-aryl-2,3-dihydro-1,5-benzothiazepine derivatives, which was testified by X-diffraction. And the possible reaction mechanism are proposed. In addition, we combined β-lactams moieties which have strong biological activities with1,5-benzothiazepines by [2+2] cycloaddition reaction, and a series of derivatives with novel structures were synthesized.The thesis includes two major parts:The first part is about literature review. The important synthetic methods, structure and chemical transformation of1,5-benzothiazepine derivatives that have been studied in China and other countries were explicated systematically; Research progress of1,2,4-triazole was also introduced.The second part is about experimental content. Major work as follows:1. Synthesis of novel chalcone containing1,2,4-triazole.Starting with acetophenone, reacted with polyformaldehyde and N,N-dimethylamine hydrochloride to form mannish base, in high yield, which was reacted with1,2,4-triazole in water to yield3-(N,N-dimethylamino)-1-aryl-propan-1-one hydrochloride. The ketone obtained reacted with aldehyde or para-substituted aldehyde to form chalcones by aldol condensation.2. Synthesis of3-arylmethylene-4-aryl-2,3-dihydro-1,5-benzothiazepine derivatives. The reaction of chalcones with2-aminothiophenol in ethanol gave a series of unexpected3-arylmethylene-4-aryl-2,3-dihydro-1,5-benzothiaz-epine derivatives.3. Synthesis of1,5-benzothiazepine-β-Lactam derivatives.Treating1,5-benzothiazepines with ketene in situ undergoing [2+2]cycloaddition reaction, in the presence of triethylamine, a series of new1,5-benzothiazepine-β-Lactams derivatives were obtained.We had got eleven new1,5-benzothiazepines and eight1,5-benzothiazepine-β-lactams. Above all, the structures of the new compounds were confirmed by elememtal analysis, IR, MS, and1H NMR spectral data. And parts of these compounds’conformation was testified by X-diffraction.