A Base Promoted Synthesis of N,N-dimethylformamidines

摘要

As a kind of important intermediates, N,N-dimethylform-amidines (1) has been widely used to synthesize nitrogen-containing heterocyclic compounds such as benzoimida-zole, quinoline,indole and quinazolines.In recent years, the synthesis of various quinazolines, as inhibitors of tyrosine kinase, has been a focus for medicinal chemists. Meanwhile Stephan Enthaler's group reported that 1 as versatile ligands exhibited potential in the zinc-catalyzed hydro-silylation of carbonyl compounds and the iron-catalyzed epoxidation of olefins. Although 1 has presented various important uses, only three reported synthesis methods were mainly used. Using N,N-dimethylformamide (DMF) and different arylamines as starting materials in the presence of Vilsmeier-Haack reagent (POCl3) can give 1 in moderate yields. This method requires anhydrous and inert atmosphere conditions, and longer reaction time, also the pollutant is produced from POCl3.1 could be also prepared in shorter reaction time from primary amines, DMF and sulfonyl chlorides.However, good selectivity of formamidine could be obtained only in the presence of 2-pyridinesulfonyl chloride. And by-products, sulfonamides, are formed from amines and other sulfonyl chlorides in this route. The synthesis strategy of 1 through the condensation of N,N-di-methylformamide dimethyl acetal (DMF-DMA) and arylamines is used in the highest frequency, because of higher yield of 1 and convenience work-up. However this method in most cases still demands longer reaction time and relative high reaction temperature. Therefore, development of a mild, efficient and low environmental impact synthetic strategy is still in strong demand. We herein report a base promoted synthesis for 1 through the nucleophilic reaction of arylamines bearing strong electron withdrawing group at o-position and imine complex produced from DMF and dimethyl sulfate.