Quinazolines. Part XX. Synthesis and stereochemistry of N-methyl-cis-perhydroquinazolin-2-ones and N-methyl-cis-perhydroquinazolines; a new conformation for cis-perhydroquinazolines

Abstract

Catalytic hydrogenation of 3,4,5,6,7,8-hexahydroquinazolin-2(1H)-one (1) and its 1- and 3-methyl derivatives [(2) and (3)] gave exclusively the cis-perhydro-derivatives (9), (11), and (10), respectively. The structures of the last two compounds were confirmed by syntheses from cis-2-p-tolylsulphonylaminocyclohexanecarboxylic acid (22). 1-Benzyl- (12) and 1,3-dimethyl-cis-perhydroquinazolin-2-one (13) and 1-methyl- (36), 3-methyl-(37), and 1,3-dimethyl-cis-perhydroquinazoline (38) were also synthesised. 1H N.m.r. spectra showed that in solution 3-methyl-cis-perhydroquinazolin-2-one (10) and 3-methyl-cis-perhydroquinazoline (37) exist predominantly in the conformation type (14), whereas the previously unobserved conformation type (19) was strongly favoured by 1-methyl- (11), 1-benzyl- (12), and 1,3-dimethyl-cis-perhydroquinazolin-2-one (13). The spectra also implied that 1-methyl- (36) and 1,3-dimethyl-cis-perhydroquinazoline (38) existed mainly in the conformation (40) [≡(19)]. Show more