A study of 3-hydroxy-1,2,3-benzotriazin-4-one and its O-methyl and O-acyl derivatives

Abstract

3-Hydroxy-1,2,3-benzotriazin-4-one, 1, was prepared by diazotization of o-aminob-enz-hydroxamic acid, 2. 3-Methoxy-1,2,3-benzotriazin-4-one, 5a, was obtained by reaction of 1 with dimethyl sulphate and was found to be stable to thermolysis. Acetylation and benzoylation of 1 yielded the N-acetoxy-5b and benzoyloxy-5c derivatives respectively. The N-benzoyloxy derivative 5c is converted into the acetate 5b by a novel 'acyl-exchange' reaction in acetic anhydride. Acid hydrolysis of 1 gives anthranilic acid, and thermolyses of 1 in amyl alcohol and aniline afford amyl anthranilate and N-phenylanthranilamide, respectively. The ketenimine 11 is postulated as an intermediate in the thermal breakdown of 1, and this is confirmed by the isolation of the Diels–Alder adduct 12 from reaction of 1 with phenyl isocyanate. Thermolysis of 1 in inert solvents affords a novel compound, 3-(o-aminobenzoyloxy)-1,2,3-benzotriazin-4-one, 6, which polymerizes when 1 is subjected to prolonged thermolysis in diglyme. 6 resisted methylation and acid hydrolysis, but underwent acyl-oxygen cleavage when diazotization of 6 was attempted and suffered 'acyl-exchange' when acylation was attempted. The formation of 6 from 1 also involves the ketenimine 11. The importance of these observations to an understanding of previously reported reactions of benzotriazinones is discussed. The o-aminobenzoyloxy derivative 6 shows potential as an o-aminobenzoylating agent.

A 15N NMR investigation of a series of benzotriazinones and related antitumour heterocycles

“…The same method was used to prepare 3-(2-chloroethyl-)1,2,3-benzotriazin-4-one (1d), 3-benzyl-1,2,3-benzotriazin-4-one (1c) 4 Methyl anthranilate was treated with hydroxylamine in the presence of sodium hydroxide to afford the o-aminobenzhydroxamic acid (6 X D H, R D OH), which was diazotized in hydrochloric acid with sodium nitrite according to the method of Ahern et al 6 to afford 3-hydroxy-1,2,3-benzotriazin-4-one (1f). Reaction of 1f with benzoyl chloride in pyridine afforded 3-benzoyloxy-1,2,3-benzotriazin-4-one (1g).…”

“…Reaction of 1f with benzoyl chloride in pyridine afforded 3-benzoyloxy-1,2,3-benzotriazin-4-one (1g). 6 …”

Anthraniloylanthranilamide (o-amino-N-(o-carbamoylphenyl)benzamide): Preparation and use as a synthetic precursor for quinazolino[1,2,3]benzotriazinones

“…3-(0-Aminobenzoy1oxy)-I ,2,3-benzotriazin-4(3H)-one (8) has recently been shown to be a potentially 0 useful reagent for o-aminobenzoylation (7). Although the versatility of this reaction has not been thoroughly demonstrated, 8 does react with primary alkylamines t o afford anthranilamides (7).…”

“…Although the versatility of this reaction has not been thoroughly demonstrated, 8 does react with primary alkylamines t o afford anthranilamides (7). When a mixture of 8 and excess anthranilaniide was refluxed in nitromethane, formation of anthraniloylanthranilamide (6) was quickly evident as adduced by tlc analysis, which also showed the presence of both the starting materials and the expected by-product, N-hydroxybenzotriazinone (90).…”

“…Evidently the 0-blocked hydroxylamine can react as a nucleophile via the N atom with equal reactivity to the N-substituted hydroxylamines. The reaction of 7 with 0-alkylhydroxylamines is a useful step in the synthesis of 3-alkyloxybenzotriazinones; diazotization of 116 affords the 3-benzyloxytriazinone (96), which was also synthesised by direct benzylation of the 3-hydroxytriazinone (9a) (7).…”