The Effect of Ortho Substituents on the Regioselective Reduction of 1-(o-Substituted phenyl)-2(1H)-pyrimidinethiones

Abstract

The reduction of various 1-phenyl-2(1H)-pyrimidinethiones substituted on the ortho and para position of the N-phenyl group by hydroxyl, methoxyl, or methyl group with metal hydride complexes (lithium aluminum hydride, lithium borohydride, or sodium borohydride)was investigated. It was found that the ratio of dihydropyrimidines to tetrahydropyrimidines depended largely upon the phenyl substituents and the metal hydride complex used. The influence of the ortho and para substituents was not observed when sodium borohydride was used. However, when lithium aluminum hydride or lithium borohydride was employed, the product ratio of the two dihydro forms and the tetrahydro form depended largely on the substituent, and an especially high regioselectivity for the 3, 6-dihydro form was observed when the ortho substituent was hydroxyl or methoxyl group. The high regioselectivity was attributed to the reaction of the metal hydride with the ortho sustituent to form initially phenaxide or a coordinated bond, followed by intramolecular hydride attack to the 6 -carbon of the pyrimidinethione to yield 3, 6-dihydro-2(1 H)-pyrimidinethiones preferentially.