Domino Reaction For One-pot Synthesis Of Functionalized 1,5-Benzodiazepine Compounds

1,5-Benzodiazepines are important classes of nitrogen-containing heterocycles with pharmacological activities,which are broadly used as analgesic,sedative,anticonvulsant,antianxiety and hypnotic agents.Due to their wide biological activity,the synthesis of these compounds has received a great deal of attention.Consequently,the design of novel reactions with unprecedented procedures for the synthesis of new classes of benzodiazepine-based molecules,as well as for multiple bonds formation using an inexpensive substrate with a simple catalytic system,remains a highly desirable and continuous goal in contemporary organic synthesis.In this context,domino reactions have emerged as a tool to realize the objective due to their efficient atom economy and green characteristics.One-pot synthesis of novel benzodiazepines via domino reaction is considered to be one of the most promising methods in the 21 st century and has certain positive significance.Our group has been devoting to developing the one-pot synthetic methodologies for benzodiazepines.The active 1,5-benzodiazepine as the basic structure,by introducing active groups such as ester groups,carboxyl groups,acyl groups,hundreds of 1,5-benzodiazepine derivatives have been successfully synthesized by various chemical processes.As part of our ongoing effort in the development of one-pot synthetic methodologies for functionalized benzodiazepine derivatives,and considering our previous results.In this communication we would like to report an efficient approach to the synthesis of novel 1,5-benzodiazepines via domino reaction.1.In this paper,the 2-thiazolyl-3,4-diester-1,5-benzodiazepine compound of the two structures of imine structure and enamine structure was obtained via domino reaction.12 novel 1,5-benzodiazepines were obtained via a domino sequence of a nucleophilic addition/ dehydration/ cyclization/ H+ shift.These reactions were achieved by reacting 1,2-phenylenediamine,2-thiazolecarboxaldehyde with diethyl acetylenedicarboxylate in Et OH.Structures of all the products were full confirmed by spectroscopic techniques.Moreover,the plausible reaction mechanism has been proposed.The influence of reaction conditions on the selectivity of target products was also studied in detail.The selectivity law of synthesis reaction was obtained,and the yield of single product was maximized.To further prove the conclusion,quantum chemical calculations were performed and DFT studies based on B3 LYP method and 6-31 G basis set were employed to carry out the study.NBO charge analysis of the substituted 1,2-phenylenediamine were carried out to justify the selective attack at the nucleophilic centers.Further,the target compounds were analyzed for NBO charge.2.A simple and efficient protocol has been developed for the synthesis of 40 novel benzodiazepines fused tricyclic or tetracyclic via three-component or domino reactions.The three-component reaction for the synthesis of novel 1,5-benzodiazepines fused tetracyclic was developed.The reaction was achieved by reacting 1,2-phenylenediamine,cyclopentane-1,3-dione with aromatic aldehydea in Et OH under room temperature and Ce Cl3 as the catalyst.The domino reaction for the synthesis of novel 1,5-benzodiazepines with new tricyclic system containing ester,carboxyl and acyl group was developed.The reaction was achieved by reacting 1,2-phenylenediamine,?-cyclodione with aldehyde derivatives in Et OH under room temperature and ?-Fe2O3@Si O2/Ce Cl3 as the catalyst.This method is operational simplicity,mild reaction conditions.Structures of all the products were full confirmed by spectroscopic techniques and by recording single crystal XRD.Moreover,the plausible reaction mechanism has been proposed.3.Various 3-acyl-1,5-benzodiazepines were synthesized via mannich four-component domino reaction.Firstly,the mannich reaction was carried out by diacetylmethane,paraformaldehyde and dimethylamine hydrochloride in ethanol with stirring at refluxing ethanol.Subsequently,the 1,2-phenylenediamine was added to the reaction mixture and stirred in 0 ?.Structures of all the products were full confirmed by spectroscopic techniques.Moreover,the plausible reaction mechanism has been proposed.