Methodology Of PIDA-mediated Construction Of1,4-Benzodiazepine Skeleton

To date, even after so many years’ development, searching novel methods for thesynthesis of heterocycles still remains as a hot topic in medicinal chemistry.1,4-Benzodiazepine skeleton, one of the key heterocyclic ring systems, has beenwidely used in many biologically important pharmaceutical agents.Iodine(III) reagents, which have been studied for many years, are still boostingthe preparation of various heterocycles because of their unique oxidative properties invarious bond formation such as C-C, C-O and C-N bond, and it has been well knownthat reactions of hypervalent iodine reagents with N-alkoxyamide compounds afford astabilized nitrenium ion as intermediate, which undergo intramolecular aromaticelectrophilic cyclization to give various N-containing heterocycles. In this thesis, theresearch mainly include the aspects below:1. According to the result of literature search and some related projects fromour group, we developed a method of synthesizing the heterocycle containing1,4-benzodiazepine skeleton through the formation of C-N bond via PIDA mediatedoxidation.2. N-Alkoxyamide compounds can afford a stabilized nitrenium ion asintermediate during the reaction of oxidative cyclization for the electronic donatingeffect of the methoxy group. So we try to apply this theory to the experiments tocomplete this intramolecular aromatic electrophilic cyclization to give variousN-containing heterocycles.3. According to the influences of electronic effect and steric effect, we provided16examples that contain different functional groups on both aryl rings in the systemof the substrates to test all the impacts of substitude groups on the reaction yield.4. For further application, the methoxy group is removed under reductivecondition. With such a kind of structure, more dibenzepin analogous can be easilyprepared.The appealing features of this method include its generality in terms of substratesscope, the mild reaction conditions and the heavy-metal-free characteristic of the keyoxidative coupling step. Moreover, the N-methoxy group in the final products can bereadily removed for futher derivatization of the amide moiety.