Study On The Condensation Cyclization Reaction Of O-amino 1,2,3-triazole With Aldehyde

N-Heterocycles are among the most significant structural units of pharmaceutical molecules,and the U.S.FDA approved drugs reveals that 59%of unique small-molecule drugs contain a N-heterocycle.Quinazolines and 1,2,3-triazoles both are very important members of the N-heterocycle family,which are widely used in biomedicine and other fields.As a combination of the above two pharmacological important N-heterocycles,quinazolino 1,2,3-triazole derivatives play an indispensable role in many fields.Some progress has been made for the synthesis of these derivatives,mainly including the reactions of azides with nitriles,alkynes and nitroene derivatives.However,most of these existed methods require the use of base or metal,with relatively harsh conditions and low atomic economy.Therefore,it is of great significance to develop a simple,efficient and green method to synthesize these fused 1,2,3-triazoles.In this thesis,mono-substituted 5-o-aminoaryl-1,2,3-triazole was used as a new nucleophilic reagent to construct quinazolino 1,2,3-triazole derivatives through cascade cyclization reactions.The main contents are as follows:1)Firstly,the applications of quinazoline derivatives,1,2,3-triazole derivatives and quinazolineo 1,2,3-triazole derivatives in the fields of medicine and pesticide have been summarized.The synthesis progresses of quinazolineo 1,2,3-triazole derivatives also have been introduced.2)A metal-free,visible-light induced cyclization reaction of 5-o-aminoaryl-1,2,3-triazoles and aldehydes to obtain quinazolino 1,2,3-triazole derivatives has been developed.Using5-o-aminophenyl-1,2,3-triazole and benzaldehyde as model substrates,photocatalyst,material ratio,solvent and reaction concentration have been screened.The optimal reaction conditions were obtained as follows:2-（1H-1,2,3-triazol-5-yl）aniline（0.3 mmol）,benzaldehyde（0.36mmol）,4Cz IPN（0.1 mol%）,DMF（1.2 m L）,and reacted in room temperature air under blue light irradiation for 24 hours,obtain the target product 5-phenyl-[1,2,3]triazolo[1,5-c]quinazoline with an 80%separation yield.Substrate scope study has been carried out under the standard conditions.In addtion,β-amino-NH-nitrogen heterocycles are also compatible with this reaction.A total of 55 target compounds was obtained.All the structures were defined by NMR and HRMS.Finally,the product was produced at gram scale,and its conversion reaction was also studied,mainly including the arylation of 1,2,3-triazole at position C（4）and the ring opening reaction.3)The silver-catalyzed cascade cyclization of 5-o-aminoaryl-1,2,3-triazoles and2-alkynylbenzaldehydes to construct pentacyclic fused isoquinoline-1,2,3-triazole-quinazoline derivatives has been studied.Using 5-o-aminophenyl-1,2,3-triazole and 2-（phenylethynyl）benzaldehyde as model substrates,solvent,temperature,catalyst type,dosage,and concentration have been screened.The optimal reaction conditions were obtained as follows:2-（1H-1,2,3-triazol-5-yl）aniline（0.2 mmol）,2-（phenylethynyl）benzaldehyde（0.2 mmol）,Ag NO₃（10 mol%）,DMF（1 m L）,and reacted at 80℃for 2 hours,The target product 6-phenyl-11b H isoquinoline[2,1-a][1,2,3]triazolo[1,5-c]quinazoline was obtained in 92%separation yield.Substrate scope study was then carried out under the standard conditions.A total of 28 target compounds was obtained.All the structures were defined by NMR and HRMS.Finally,the experiment of gram scale preparation was carried out.