Synthesis Of Benzoheterocycles Based On O-Aminobenzyl Chlorides

Nitrogen-containing six-membered heterocycles as privileged scaffold are widely found in natural products and pharmaceuticals.Therefore,it is highly desirable to develop mild protocols to access heterocyclic compounds with biological activity.Among the established methods to construct six-membered N-heterocycles,annulation reactions are probably the most straightforward methods and received considerable attention.Based on the property of o-aminobenzyl chlorides,in the present dissertation,two kinds of six-membered N-heterocycles were obtained with high efficiency.We have developed a base-promoted formal[4+2]cycloaddition of in situ formed aza-o-quinone methides from o-aminobenzyl chlorides with hexahydro-1,3,5-triazines to synthesize a series of tetrahydroquinazoline derivatives in moderate to good yields.This protocol features mild reaction conditions,a wide substrate scope and good functional group tolerance.The reaction can be performed on the gram scale.Based on the previous work,we found that o-aminobenzyl chlorides can undergo intramolecular cyclization in the presence of base.We identified the optimal reaction conditions through investigating the reaction parmeters such as bases and solvents.This approach provides easy access to a series of benzoxazine derivatives in moderate to excellent yields under mild reaction conditions.All the desired products were fully characterized by ¹H NMR,¹³C NMR,HRMS,and X-ray diffraction analysis.