Multicomponent Reactions For The Synthesis Of N-Heterocyclics Under Metal-Free Conditions

The nitrogen-containing heterocyclic compound has become an important part of heterocyclic compounds due to its particular physical and chemical properties,biological activity and drug value.They are widely used in chemistry,biology,medicine and other fields,especially in pharmaceutical chemistry.The paper researches on the synthesis of N-heterocyclics via multi-component reaction under metal-free conditions.The detailed researches were described as follows:1.A multi-component procedure for the formation of nitrogen-containing heterocycles based on the direct functionalization of C-H bonds under mild conditions with cheap ammonium salts as nitrogen sources was described.Quinazoline compounds were successfully synthesized by the four-component reaction of anilines,aromatic aldehydes and ammonium iodide.The C-H bond ortho to the amino group in anilines was directly functionalized and further cyclized to obtain the target product under metal-free conditions.Two aldehydes were involved in this reaction and ammonium iodide was used as one of the nitrogen sources,which provided a simple and efficient new method for the synthesis of quinazolines.2.An efficient base-promoted aerobic oxidation reaction for the synthesis of fused 1,3,5-triazines from 2-aminobenzimidazoles,aromatic aldehydes,and ammonium iodide under metal-free conditions has been developed.In this multi-component protocol,ammonium iodide served as a convenient nitrogen source and four C-N bonds were formed in one pot.Various indazole fused 1,3,5-triazines and pyrimido[4,5-b]indoles were selectively formed in the simple system.This method provided an efficient approach to various substituted fused 1,3,5-triazines from readily available raw materials under simple reaction conditions.3.An efficient synthesis of pyrimidines and pyridines has been developed from readily available aromatic ketones,aldehydes and ammonium salts under transition-metal-free conditions.In this strategy,ammonium salts were used as nitrogen sources and only water was generated as a nontoxic byproduct.A catalytic amount of Na IO₄ played an important role in the selectivity control and various pyrimidines were formed in reasonable yields,whereas trisubstituted pyridines were dominantly formed in its absence.Transition-metal-free conditions,high selectivity,and the need for simple substrates and cheap nitrogen sources are some of the advantages of this transformation.This method provides an efficient approach to various substituted pyrimidines and pyridines under simple reaction conditions via MCR.4.An efficient synthesis of pyrroles has been developed via three-component ordered annulation of amines,ketones,and nitrovinylarenes under metal-and additive free conditions.Substituted indoles were selectively formed from the same starting materials via a one-pot,two-step process when the reaction was carried out under the oxidative conditions of I₂/DMSO without the aid of metal-catalyst.This controllable process has the advantages of simple conditions,readily available raw materials,good scope and generality,which provides new routes to functionalized pyrroles and indoles under metal-free conditions.5.An effective strategy for constructing?-carboline through direct functionalization of indole C-H bond under metal-free conditions has been reported.The multi-component methodology uses simple ammonium salts,2-(1H-indol-3-yl)cyclohexan-1-ones and benzaldehydes as starting material.By controlling the reaction conditions,the indozo[2,3-c]quinoline compounds can be selectively obtained from the same raw material.The present work provides a novel synthesis of carboline and indozo[2,3-c]quinolone with broad functional grounp tolerance.6.An novel synthesis of pyrrole[2,3-c]quinolines from2-(1H-indol-3-yl)cyclohexan-1-one,amines and aldehydes under NH₄I-catalyzed conditions has been developed.The multicomponent reaction has good functional group tolerance and selectivity,which provides a new way for the formation of important pyrrole[2,3-c]quinoline compounds.