Chapter 27 - Bicyclic compounds containing a pyridine; Isoquinoline and its derivatives

Abstract

Publisher Summary This chapter presents major advances in isoquinoline chemistry in the recent years.The Bischler–Napieralski reaction remains the most frequently employed method for the synthesis of isoquinolines. The reaction involves the cyclodehydration of N -acyl-2-phenethylamines with a Lewis acid in a solvent. The product is a 3,4-dihydroisoquinoline. The cyclodesulfhurization of thioamides is employed as a mild alternative in the Bischler–Napieralski reaction. Unsaturated carbamate esters can be converted into fused tetrahydroisoquinolines. These reactions are believed to proceed via N -acyliminium salt intermediates. Isonitriles, which can be prepared by the reaction of dichlorocarbene on 2-phenethylamines, produce 3, 4-dihydroisoquinolines in good yield when cyclized with certain Lewis acids. Isonitriles react with acyl halides under mild conditions in the presence of a silver salt to give, via the ketoimidoyl halide, good overall yields of 1-acyl-3,4-dihydroisoquinolines. The importance of silver trifluoromethanesulfonate has been recorded in the reaction of allylbenzenes with nitriles. The triflate anion is a poor nucleophile and its limited association with the intermediate nitrilium salt offers little hindrance to cyclization and formation of the 3,4-dihydroisoquinoline.