Tetrahydrofolate coenzyme models: synthesis of tetrahydroimidazoisoquinolines and tetrahydroimidazoquinolines

Abstract

The new dihydroimidazoles 3-methyl-1,5,6,10b-tetrahydroimidazo[5,1-a]isoquinoline and 1-methyl-3,3a,4,5-tetrahydroimidazo[1,5-a]quinoline are efficiently and conveniently prepared from isoquinoline and quinoline, via 1-aminomethyl-1,2,3,4-tetrahydroisoquinoline and 2-aminomethyl-1,2,3,4-tetrahydroquinoline and 2-aminomethyl-1,2,3,4-tetrahydroquinoline, respectively. Deprotonation of the fused dihydroimidazoles at the methyl substituent leads to homologation via C-alkylation, C-acylatioin, or C-phosphonylation–condensation. The properties of the tetrahydroimidazo[5,1-a]isoquinolines and tetrahydroimidazo[1,5-a]quinolines towards reducing agents mirror those of monocyclic dihydroimidazoles, affording aminomethyl-isoquinolines and -quinolines, respectively.