A definitive synthesis of 2-[(5-methyl-s-triazolo[4,3-c]quinazolin-3-yl)thio]-N-benzylacetanilide and other reactions of its precursors

Abstract

Treatment of 2-methyl-4-chloroquinazoline 2 with hydrazine gave 2-methyl-4-hydrazinoquinazoline 3 which was converted to 5-methyl-3-mercapto-s-triazolo[4,3-c]quinazoline 4, followed by S-alkylation with chloro-N-benzylacetanilide to give 6. The hydrazine 3 was converted to the hydrazone 9 with acetone, to 3,5-dimethyltriazolo[4,3-c]-quinazoline 10 with acetic anhydride, and to 5-methyl-s-tetrazolo[1,5-c]-quinazoline 12 via a nitroso intermediate 11 with nitrous acid. Compound 3 and its derivatives 4, 6, 10, and 12 differed from those alleged to have these structures. The previously reported compounds cannot have these structures since X-ray diffraction studies established that the structure of the common precursor is 3. The mercaptotriazole 4 was air oxidized to the disulfide 20 and hydrolyzed to 2-methyl-3-hydrazinothiocarbony]-4(3H)-quinazolinone 19. The reaction of 4 with carbon disulfide gave a side-product for which the 5-methylquinazolino[3,4-c]-1,2,4-thiadiazol-2-thione 21 is suggested. The 1H nmr chemical shifts of the quinazoline methyl substituent are near δ 3 ppm in the fully aromatic compounds and at higher field when the heterocycle is non-aromatic.