Study On The Green Method Of Unsymmetric 1,3,5-triazine And Quinazolinone

N-heterocyclic compounds have been widely used in medicine,pesticides,organic functional materials and other fields,because of their physiological and pharmacological activity.Transition-metal-catalyzed synthesis of N-heterocyclic compounds is still the main strategy from readily available substrates in the previous methods;but transition-metal catalysis will lead to the transition metal residue in the products inevitably,which hindered its application in the synthesis of drug molecule.Therefore,the development of metal-free catalysis,visible light catalysis and other green synthetic means are of great significance.Given this,we studied the green synthesis of 1,3,5-triazin-2-amine and quinazolinone,which have wide range of biological activity,and the results are as follows:A simple and efficient method for the direct synthesis of unsymmetrically substituted 1,3,5-triazin-2-amines via base-mediated cyclization of imidates,guanidines with amides or aldehydes has been developed.The unsymmetrically substituted 1,3,5-triazine derivatives were hard to prepare directly from readily available substrates in the previous methods.And the method we developded is one-pot reaction with metal-free,is also a green synthetic method.A novel reaction mechanism is also proposed for the synthesis of 4-aryl-1,3,5-triazin-2-amines from imidates,guanidines and DMF;the formyl group of DMF serves as the C-H supplier in our work.Then we use DMA and aldehydes to replace DMF,and unsymmetrically disubstituted 1,3,5-triazin-2-amine derivatives are also synthesized successfully.This method can tolerate various functional groups,can synthesize unymmetric substituted 1,3,5-triazines and symmetrically substituted 1,3,5-triazines by altering the starting material.The synthesis of unsymmetrically substituted 1,3,5-triazin-2-amines with different bioactive groups is significant for the research of new drugs,this method will have a promising application in the direct synthesis of 1,3,5-triazin-2-amine drugs.It is an important approach to synthesize quinazolinones by Ullman coupling of o-halobenzamide with benzylamine,and oxidative ring-closing reaction of relative intermediate sequentially.This approach usually needed to be carried out under heating and transition metal catalyzed conditions.However,the synthesis of quinazolinones from o-chlorobenzamides and benzylamines by visible-light-induced means has not been reported.Then we developed a method for synthesizing quinazolinone from o-chlorobenzamide and benzylamine with visible light,and O2 act as oxidants.This reaction include two sequential procedrues:o-chlorobenzamide react with benzylamine to lead to Ullman coupling produc,then Ullman coupling product was Oxidized to form the corresponding quinazoline compounds.The reaction conditions of the method are mild,and the product is easy to handle.Visible-light is a clean energy,and oxygen is also a green oxidant,so the method is also a green synthesis method.