Synthetic Study Of Benzoazepines Based On Triazole-Containing Para-Quinone Methides

The benzoazepine skeleton and triazole structural units are widely present in drug molecules.The construction of related skeletal structures and the investigation of their physiological activity have attracted the interest of many synthetic chemists and medicinal chemists.For example,with good pharmacological activity,benzoazepine derivatives have been used in clinical medicines as anti-anxiety,hypnotic and sedative drugs,and for the treatment of cardiovascular diseases.Triazole compounds have a broad spectrum of biological activities,such as anti-tumor,anti-inflammatory,antibacterial,antithrombotic,antiplatelet,anticonvulsant,etc.Many of such derivatives have been developed and applied as fungicides,drugs,and plant growth regulators.As well known,the combination and grafting of different biopharmaceutical groups is an effective way to develop new bioactive precursors.Therefore,the design and synthesis of compounds containing benzoazepine and triazole heterocycles are of great significance for medicinal chemistry research.para-Quinone methides are a type of benzoquinone derivatives featuring unique six-membered cyclic bis-vinylogous enone moiety,whose structural unit widely exists in natural products and pharmaceutical molecules and constitutes the key intermediate for many medicinal chemistry and biosynthesis.In recent years,the 1,6-conjugated addition reaction of para-quinone methides and its annulation reactions have gained considerable attention from chemists,showing the importance that para-quinone methides are playing as one class of electrophilic synthons for the design of synthetic methodologies in organic chemistry.In this thesis,focusing on the synthesis of pharmacologically potential benzoazepine-derived triazole heterocyclic compounds,a novel aza-1,6-conjugate addition reaction of triazole-containing para-quinone methides has been designed and developed,providing a new approach to construct the structurally novel heterocycles.The current thesis is mainly divided into the following three parts:The first part: Focusing on the synthesis of benzoazepine-derived compounds,a brief review of the research progress in the synthesis of benzoxazepine-type and benzodiazepine-type derivatives is presented,wherein various methods have been described,particularly for constructing seven-membered heterocyclic units.The second part: The research progress on reactions using N-sulfonyl-1,2,3-triazole compounds is included.The third part: The synthetic study of benzoazepine-fused triazole heterocyclic compounds is described in detail.Based on our recent interest in the chemistry of paraquinone methides,together with the unique characteristic of triazole chemistry,a novel type of para-quinone methides containing N-sulfonyl-1,2,3-triazole group is designed and prepared,and its reactivity under acidic catalytic conditions has been deeply investigated to achieve a series of benzoazepine-derived triazoles.Besides,an unexpected formal [3+2]-cycloaddition product could be obtained under the conditions of metal catalysis at high temperature,to a certain extent,showing the diverse reactivities of N-sulfonyl-1,2,3-triazole-derived para-quinone methides in organic synthesis.