Studies on Quinazoline 3-Oxide.

Abstract

Catalytic reduction of quinazoline 3-oxide (I) using Raney nickel catalyst results in formation of quinazoline (II) by absorption of one mole of hydrogen and 3, 4-dihydroquinazoline (V) by absorption of two moles of hydrogen. Deoxygenation of (I) with phosphoryl chloride also gives (II). Reaction of (I) with anionoid reagents was examined. The Reissert reaction and the reaction with acetic anhydride failed to form the anticipated 4-substituted compound and a ring fission of the pyrimidine portion occurred, affording 2'-(benzoyloxyiminomethyl)-benzanilide (VIII) and o-isocyanobenzonitrile (IX). Formation of these compounds was presumed to follow the route shown in Chart 2. (I) also undergoes fission of the ring in alkali hydroxide solution at room temperature to form 2'-(hydroxyiminomethyl) formanilide (X). In contrast to the foregoing reactions, application of hydrogen cyanide, sodium hydrogensulfite, and hydrazine, which have lower reactivity as anionoid reagents than those mentioned above, to (I) resulted in the formation of a corresponding 4-quinazolinecarbonitrile (XII), sodium 4-quinazolinesulfonate (XIII), and 4-hydrazinoquinazoline (XIV). These reagents did not react with the 2-position of (VIII) and only hydrazine reacted with (VIII) to form 4-hydrazinoquinazoline 1-oxide (XI). These experimental results indicate that the nucleophilic acitivity of 4-position in (I) is greater than that of 2-position in (VII). It was thereby concluded that the polar effect of the N-oxide group in (I), together with the effect of ring-nitrogen and the fused benzene ring, markedly increases the nucleophilic activity of 4-position in the quinazoline ring system. On the other hand, stability of the ring has been markedly decreased and facile ring fission occurs between 2-and 3-positions.