Novel Syntheses of Hexahydropyrimidines and Tetrahydroquinazolines

Abstract

1-Benzotriazolylmethyl-3-propylhexahydropyrimidine (1) and 1,3-bis(1H-1,2,3-benzotriazol-1-ylmethyl)-1,2,3,4-tetrahydroquinazoline (3) were readily prepared by reactions of N-propyl-1,3-propanediamine or 2-aminobenzylamine with benzotriazole and formaldehyde, respectively. Intermediate 1 reacted with alkyl and aryl Grignard reagents to produce N,N'-unsymmetrically substituted hexahydropyrimidines 2a,b in 90 and 92% yields, respectively. Nucleophilic substitutions of 3 with Grignard reagents, allylsilane, and triethyl phosphite gave N,N'-disubstituted 1,2,3,4-tetrahydroquinazolines 4a-f, 5, and 6 in good to excellent yields. Successive treatment of 3 with two different Grignard reagents in one-pot reaction led regiospecifically to N,N'-unsymmetrically substituted tetrahydroquinazoline derivatives 8a,b.