The Synthesis Of Tetrazoles And Methylated Tetrazoles

With its unique properties, tetrazole derivatives has been applied in various fields such as energetic materials, biomedical, coordination chemistry, pharmacology and so on. Therefore, synthesis of tetrazole derivatives has become a research hotspot.Based on the achievement of many other literatures, this paper illustrates a synthesis route of5-substitued-1H tetrazoles which uses nitriles, NaN3, Tetrabutylammonium bromide(TBAB) and without any organic solvents. According to the experiments, the optimised reaction conditione are:n (nitriles):n (NaN3):n (TBAB)=1:1.2:1.2, in the temperature of105℃. A series of nitriles were used to explore the scope of this methodology such as benzonitrile and other substrates that contains pyridine、pyrazine or other heterocyclic rings. Among all the substrates we tried, most of them were obtained in excellent yields, we got the yield of62%to98%, The benzonitrile substrates bearing electron-withdrawing groups all afforded the corresponding5-substitued1H-tetrazoles in good yields. We have proposed the plausible mechanism of this reaction is typical [2+3] dipolar cycloaddition.Herein, we also desired an efficient method for the N-methylation of5-substituted1H-tetrazoles with DMC. In this method, DMC was used as a nontoxic, safe and biodegradable methylating reagent, DABCO was used as a base, DMF as solvent. Through a series of experiments, we found the the optimised reaction conditions:5-substituted1H-tetrazoles was5mmol, DMC was4mL, DABCO was0.5mmol, DMF was6mL, under the temperature of130℃. A series of5-substituted1H-tetrazoles were studied to examine the structure reactivity profile, a variety of substrates bearing both aliphatic and aromatic substituents afforded N-methyl tetrazoles in yields of61%to98%. The yields which most of the substrates bearing aromatic substituents afforded were over90%. This Synthesis route also has good selectivity. A plausible mechanism is also proposed for N-methyl reaction in this paper.In addition, the structure of nearly all the product were confirmed by1H-NMR、13C-NMR and MS.