Synthesis Of Nitrogen Heterocyclic Compounds Based On Isothiocyanates

Nitrogen heterocyclic compounds are important structural units existed in many drug molecules,natural products and bioactive substances,and are also common intermediates in organic synthesis.The nitrogen-containing heterocyclic compounds have many properties and are widely used in various fields.Pyrazolo[1,5-a][1,3,5]triazine and quinazolinone with unique biological and pharmaceutical activities are one of the important nitrogen heterocyclic compounds.Because of the great value of these compounds in the field of chemical biology and medicine,it is a hot topic to develop green and efficient methods for the synthesis of nitrogen-containing heterocyclic compounds.In this paper,we focus on the development of efficient and simple methods for the synthesis of pyrazolo[1,5-a][1,3,5]triazines and quinazolinones.Specifically,it can be divided into the following two parts:1.A new photocatalyst-free visible-light-promoted strategy for the synthesis of pyrazolo[1,5-a][1,3,5]triazine-2,4-diamines via the formation of electron donor-acceptor(EDA)complexes is reported.The in situ generated pyrazolthiourea intermediates from 1H-pyrazol-3-amines and isothiocyanates undergo the formal [4+2] annulation with 1,1,3,3-tetramethylguanidines(TMG)to deliver the corresponding products involving in three C-N bonds formation in one pot.The formation of EDA complex from pyrazolthiourea and TMG is confirmed by UV-Visible spectrophotometer and NMR experiments.Moreover,this mild reaction proceeds in the absence of any external transition metals,oxidants,bases and ligands.This efficient methodology for preparing purine analogues pyrazolo[1,5-a][1,3,5]triazine-2,4-diamines provides the potential synthetic applications in the field of drug research and development.2.On the basis of the first work,we have designed and successfully developed a one-step method for the synthesis of 2-thio-quinazolinones using 2-aminobenzamides,isothiocyanates and bromo-esters as raw materials under thermal conditions.Compared with the traditional methods,the reaction proceeds under mild reaction conditions without the addition of any catalyst,base,ligand,oxidant and so on.The reaction involves the cleavage of C-N bond and the formation of C-N bond.The raw materials are economical and easy to obtain.In addition,the reaction has potential applications in drug screening and modification.