Synthesis Of Nitrogenous Heterocyclic Compounds Catalyzed By Organic Phosphonic Acid

1,2,4,5-tetra-substituted imidazoles,2-substituted benzimidazoles andbis(indolyl)methanes are important nitrogenous heterocyclic compounds and they have veryimportant biological activities. In recent years, they have been aroused considerable wideconcern by the chemists.In recently, the organocatalysts have become a hot topic in the field of organic chemistry.With a wide range of applications in the synthesis of chiral drugs, related to the agriculturalchemical products as well as synthesis of fine chemicals and other areas. Organic phosphonicacid as a Br nsted acid catalyst, has been developing rapidly in recent years, and hassuccessfully catalyzed many reactions.In this thesis, the organic phosphoric acid catalyzed one-pot, four component reactions ofbenzil, aldehydes, primary amines and ammonium acetate synthesis of1,2,4,5-tetra-substituted imidazolesands, catalyzed ortho-phenylenediamine and aldehydesynthesis of2-substituted benzimidazole compounds and catalyzed indole with aldehyde orketone synthesis of bis(indolyl)methanes are studied. Mainly include the following threeparts.In the first part, the organic phosphonic acid as a catalyst, four component tandemreaction of benzil, aldehyde, primary amine and ammonium acetate was studied. Firstly, fivekinds of different organic phosphonic acid that can be stable in the air were synthesized, andchoose two of these catalysts for synthesis of1,2,4,5-tetra-substituted imidazolesands. Theoptimization reaction conditions were carried out, providing20kinds of1,2,4,5-tetra-substituted imidazoles in yield of17-98%. Meanwhile, the catalytic activity oforganic phosphonic acid and other proton acids and Lewis acids for synthesis of1,2,4,5-tetra-substituted imidazole were compared. Confirming that the organic phosphonicacid in this reaction has higher catalytic activity than proton acids and Lewis acids. Finally,we proposed the Br nsted acid and Lewis base synergistic catalytic mechanism of organicphosphonic acid.In the second part, the organic phosphonic acid catalyzed ortho-phenylenediamine andaldehyde synthesis of2-substituted benzimidazole compounds was studied. The influence ofcatalysts structure and dosage, reaction solvent and reaction time on the reaction wereinvestigated, the optimal reaction conditions were obtained, giving23kinds of2-substitutedbenzimidazoles in yield of17-98%. An acid and alkali bifunctional catalytic mechanism ofthe organic phosphonic acid was proposed, in the catalytic process, an eight-membered cyclictransition state was generated.In the third part, the organic phosphonic acid catalyzed indole with aldehyde and ketonesynthesis of bis(indolyl)methanes was studied, the catalytic effect of different catalysts on the reaction were determined. In the optimal reaction conditions, the yield of target compoundwas up to98%while the catalyst load was only1mol%, and providing23kinds ofbis(indolyl)methanes in17-98%yield. Finally, on the basis of previous studies, an acidcatalyzed mechanism that organic phosphonic acid as a Br nsted acid providing a proton inthe catalytic process was proposed.In summary, organic phosphonic acid as a organocatalyst, has the capable of synthesis ofa series of important nitrogenous heterocyclic compounds, and can be obtained the desiredcompounds in a high yield. Through exploring the catalytic activities of the organicphosphonic acid, we broadened the range of applications. Moreover, by this research can befound that organic phosphonic acid catalyst is air-stable, environmentally friendly, and canprovide some basis for the future applications.