Azo Carbocations Tricyclic Type Triazole And Miscellaneous The Zhuo Derivatives Synthesis Applied Research

Benzodiazepines has drawn much attention since they have been found to exhibit a wide spectrum of biological activities on centre nervous system (CNS). Much research work has been devoted to their synthesis and activities, which indicated the additional triazole ring annulated to the azepine can provide more satisfying metabolic stability and novel pharmacological properties. According to the design principle of drugs, exchanging the nitrogen atom in the azepine with oxygen or sulfur may improve the activities and reduce the toxicity. The present thesis was concentrated on the construction of the novel tricyclic triazoloazepines or triazoloxazepines via the polar cycloaddition of bicyclic 1-aza-2-azoniaallenium ion to the nitriles and following spontaneous 1,2-shift.The first chapter is a brief review on the research situation of tricyclic azepines and wide application of 1,3-cycloaddition and 1-aza-2-azoniaallenium ion in the synthesis of five-membered heterocyclic compounds.The second chapter is about the sythesis of furo[3,2-c][1,2,4] triazolo[1,5-a] azepinium salts and furo[2,3-f][1,2,4] triazolo[1,5-a]azepinum picrates. We start from the chlorination of 3-methyl-6,7-dihydro-5H-benzofuran-4-one 2,4,6-trichlorophenyl hydrazone, however, under a variety of condition we couldn't get a chlorinated product in pure form. Therefore, we performed chlorination and the futher reaction in a one-pot manner. The 1-aza-2-azoniaallenium ion generated in situ underwent the polar cycloaddition with nitriles and spontaneous 1,2-shift of methylene, and then provided the furo[3,2-c][1,2,4] triazolo[1,5-a] azepinium salts. To improve the yield, we switched to another protocol by using theα-acetoxy azo compounds as the precursor of the 1-aza-2-azoniaallenium ion. The cycloaddition of 1-aza-2-azoniaallenium ion to the nitriles with the following 1,2-shift of furyl and hydrolysis under the basic condition gave the furo[2,3-f][1,2,4] triazolo [1,5-a]azepinium picrates. The structure of the product was confirmed by the X-ray structural diffraction analysis and biological activity was tested. The mechanism of polar cycloaddtion and 1,2-shift was also discussed.In chaper three, we introduced the synthesis of the 2-phenoxyphenyl substituted 6,7-dihydro-5H-furo[3,2-c][1,2,4] triazolo[1,5-a]azepine and 5,6-dihydro-4H-benzo[f] [1,2,4] triazolo[1,5-a]azepine derivatives. The target structures were constructed via the cycloaddtion of bicyclic 1-aza-2-azoniaallenium ion to the phenoxybenzonitriles and the following ring enlargement. The fourth chapter was concentrated on the synthesis of 4,5-dihydro-[1,2,4] triazolo[3,2-d][1,5] benzoxazepine derivatives. Base on the reaction concerning cycloaddtion and ring enlargement, we chose hydrazones of 6-methyl-2-phenylchroman-4-one, 6-methoxy-2-phenylchroman-4-one and5,7-dimethylchroman-4-one as starting materials for the synthesis of target molecules. Finally, we achieved oxazepine compounds or decomposed product 5-styryl substituted 1H-1,2,4-triazole derivatives. The structures of products and byproducts were confirmed by the X-ray structural diffraction analysis and ~1H COSY spectrum.In chapter five, we discussed the synthesis of pyrido[3,2-c][1,2,4] triazolo[1,5-a] azepine 8-oxides. We started from the 7,8-dihydroquinolin-5(6H)-one, which was then converted to theα-chloroazo compound by two steps and subsequently underwent the cycloaddition to nitriles and rearrangement. Finally, we got a mixture of two products derived from 1,2-shift of pyridyl and methylene respectively. By using the same protocol, we can get the pyrido[3,2-c][1,2,4] triazolo[1,5-a]azepine 8-oxide as sole product starting from the N-oxide 7,8-dihydroquinolin-5(6H)-one.The sixth chapter aims at the synthesis of novel thienotriazolothioazepine. We converted the 4H-thieno[3,2-c]thiopyran-7(6H)-one toα-substituted azo compounds by two steps, which served as the precursor of 1-aza-2-azoniaallenium ion. Although we performed cycloaddition and ring enlargement in a variety of condition, we couldn't achieve the synthesis of the target compounds.The chapter seven is the experimental section, which record the synthesis of all the compounds and the corresponding spectra data.