Constructing Nitrogen-Containing Heterocycles Via Transition-Metal-Free Tandem Reaction

Heterocyclic chemistry, which contains hundreds of compounds, is an important branch of organic chemistry. According to the statistics, the number of heterocyclic compounds occupies one third in all discovered organic compounds. Hence, heterocyclic compounds play an essential role in almost every area of organic chemistry.Nitrogen-containing heterocycles are compounds that are researched frequently because of their special biological properties, low toxicity and highly absorb ability. Therefore, they are worked as structure units of medicine and pesticide, and become more and more significance in daily life of human.Benzo[4,5]imidazo[1,2-α]quinazoline and dibenzodiazepine derivatives, as members of nitrogen-containing heterocycles, possess amounts of pharmacological activities, to name a few, anticancer, analgesic/anti-inflammatory activities, specific PET tracer for imaging of Tau Pathologies and treating schizophrenia and insomnia. Especially, since Clozapine as a listed-drug which treat schizophrenia has appeared in the market, the scaffold of dibenzodiazepine has been studied extensively. However, reviewing previous literatures, we find the traditional synthetic methods of benzo[4,5]imidazo[1,2-α]quinazoline and dibenzodiazepine derivatives are not plentiful, and multi-step reations are often utilized. Moreover, transition-metal catalysts are usually key elements in those conventional methods. Those limitations block the application of those methods in industrial setting.This paper proposes cascade strategy for construction of benzo[4,5]imidazo[1,2-α]quinazoline and dibenzodiazepine skeletons via a transition metal-free process in the first time. The test demonstrates this method is an efficient and facile one with excellent yields. Additively, transition-metal catalysts are banned to use in our reaction. In the process of constructing dibenzodiazepine derivatives, we innovatively synthesize the skeleton of the listed-drug-Clozapine with one-pot strategy. Protecting group-Ts produces the irreplaceable effect in the reaction.Eventually, we construct benzo[4,5]imidazo[1,2-α]quinazoline and dibenzodiazepine derivatives with over 30 different compounds. And the mechanism of reaction is also discussed.