Study On The Cross-dehydrocoupling Reaction Of Purine Derivatives And Thioethers

Purine derivatives are an important class of compounds in the pharmaceutical industry,which exist in many drugs,natural products and bioactive compounds.Traditionally,the synthesis of N9 alkylated purine derivatives mainly includes substitution reaction and addition reaction,both of which have complicated steps and harsh conditions.The cross dehydrogenation coupling reaction can construct chemical bonds such as C-C,C-N,and C-O in one step without pretreatment of the reaction substrate.It is green and efficient.Once reported,it has attracted widespread attention from chemical researchers.In the past ten years,the formation of C-N bonds through the cross dehydrogenation coupling reaction has been extensively studied.A large number of studies have shown that α-(sp3)C-H at the ortho position of heteroatoms has excellent reactivity.In the past decades,researches on the cross dehydrogenation coupling reaction at the ortho position of heteroatoms have mostly focused on O and N.As a common active group,thioether structure is also common in many drugs.The introduction of thioether group into hcicrocyciic compound can increase the liposolubility of the host compound.But,the formation of C-N bonds by the cross dehydrogenation coupling reaction at the ortho position of S has not been systematic reported.Thence,to develop a new protocol to achieve the cross-dehydrogenation coupling of purine derivative and sulfides is great important.In this paper,6-chloropurine and diethyl sulfide are used as the reaction substrate to explore the optimal reaction conditions.With iodobenzene diacetic acid as the oxidant,the cross-desorption of purine derivatives and sulfide is successfully achieved without any catalyst.This method has a wide range of substrates,and is not only suitable for various purine derivatives,but also nitrogen-containing heterocyclic compounds such as benzimidazole and benzotriazole can also obtain the target product with good yield;this reaction has good regioselectivity,mainly it reacts at the N9 position of the purine without the production of N7 isomers.In addition,when reacting with asymmetric thioethers,the reaction occurs preferentially at the benzylic position,followed by the secondary carbon position,the primary carbon position is less reactive,and the tertiary carbon position is not reaction.Through this reaction scheme,34 heterocyclic compounds with thioether structure have been successfully prepared with moderate to good yields,and passed 1H NMR,13C NMR,HRMS and IR the obtained compounds were characterized by other means.