Studies On The [3 + 2] Cycloaddition Of Aryl Diazonium Salts With Diazo Carbonyl Compounds And Diazoacetonitrile

The [3 + 2] cycloaddition reaction between aryl diazonium salts and diazonium compounds containing a reactive hydrogen at the ?-position provides a simple and efficient strategy for the construction of functional tetrazoles.At present,tetrazolium compounds containing monofluoromethyl or cyano groups have not been reported,and the regiodivergent synthesis of tetrazoles has been a significant challenge in this field.This thesis includes two parts:The first part of the work is to realize the [3 + 2] dipolar cycloaddition reaction between aryl diazonium salts and diazo carbonyl compounds.A series of2-aryl-5-carbonyltetrazoles were synthesized in good to high yields(46–92%)with excellent regioselectivity.In addition,one-pot diazotization / cycloaddition conversion from aromatic amines to tetrazoliums has also proven feasible.Finally,a series of 2-aryl-5-monofluoromethyltetrazoles were prepared in a total yield of 42–74%through further synthetic transformation and an analogue of a P2X3 receptor antagonist was synthesized successfully.The second part of the work is to develop the [3 + 2] dipolar cycloaddition reaction of aryl diazonium salts with diazo acetonitrile and synthesize a series of cyano-substituted tetrazoles.It was found that a series of 2-aryl-5-cyanotetrazoles can be synthesized in high yields(84–97%)with excellent regioselectivity(more than20:1)when 5 mol% silver acetate was used as the catalyst,whereas1-aryl-5-cyanotetrazoles can be obtained in moderate yields and regioselectivity without silver acetate.In addition,one-pot diazotization / cycloaddition conversion from aromatic amines to tetrazoles is still feasible and analogues of P2X3 receptor antagonist were systhesized successfully.Finally,the reason for the energy difference between the two reaction pathways was explained by density functional theory calculations.