Synthesis Of 11-Aryl Thio/Iododibenzodiazepines Based On Tandem Cyclization Of O-Isocyanodiaryl Amines

Dibenzodiazepine derivatives,which have unusual effects in terms of antitumour,anticholinergic,antidopamine,antipsychotic,antioxidant and antiprotease activities,are important seven-membered N-heterocycles and have therefore received much attention.For example,clozapine can be used to treat schizophrenia.After modifying the core structure of clozapine,it was found that the modified molecular structure showed good affinity for dopamine receptors.The performance of the molecule can be changed by introducing different functional groups into the dibenzazepine skeleton.Therefore,structural modification of these compounds has received considerable attention.In this paper,we first reviewed the synthetic methods for dibenzodiazepines,as well as the research progress in aryl thioetherification and iodocyclization.The main research work of this thesis was then presented,covering the following two sections.1.The Ag I-catalyzed tandem thioetherization/cyclization reaction of o-isocyanodiaryl amines was investigated for the efficient synthesis of 11-arylthiodibenzodiazepines.The method was free from the use of bases,ligands,oxidants and other additives.The reaction exhibits wide range of substrates and simple operation.Diphenyl diselenide could also work under the same conditions,but the yield of the product was relatively low.2.Using I₂ as an iodine source and TBHP as an oxidant,a tandem iodocyclization method based on o-isocyanodiaryl amines has been developed to efficiently synthesize 11-iododibenzodiazepines.The method has good substrate suitability and can effectively undergo gram-scale reaction.The 11-iododibenzodiazepine contains highly reactive C–I bond and could undergo a variety of transformations,such as achieving its reaction with phenylboronic acid,p-chlorophenylacetylene,methyl 2,2-difluoro-2-（fluorosulfonyl）acetate（Chen’s reagent）,acetophenone,phenol and benzenethiol to synthesize a series of multifunctionalized dibenzodiazepines.It provides a good foundation for the applications of dibenzodiazepine derivatives in biological and pharmaceutical fields.