1.2.4- benzotriazines, formation

Direct amination of quinoxalinones with hydroxylamine-O-sulfonic acid produces the 1-amino derivatives (135) in 70-80% yield, and subsequent oxidation with lead tetraacetate gives the 1,2,4-benzotriazines (138). Benzotriazine formation probably involves the formation of an intermediate nitrene (136), ring expansion to a benzo-triazepinone (137) and subsequent loss of carbon monoxide. The nitrene (136 R = Ph) was trapped as the sulfoximide 139 when the oxidation was carried out in the presence of dimethyl sulfoxide.147... 

The formation of transient benzazetidinones (251) in the photolysis and thermolysis of benzotriazin-4-ones (250) is well established (76AHC215) and the highly hindered adamantyl derivative has actually been isolated from flash pyrolysis of 4-adamantylbenzotriazinone (73JCS(Pl)868). A second route to such hindered benzazetidinones involves cyclization of the iminoketene valence tautomer (252 R = Bu ), the latter being generated by deprotonation of the anthranilium salts (253) (71JA1543). 

Lead tetraacetate oxidation of 3-substituted 1- and 2-aminoindazoles 6 and 7, has been shown by Rees to result in rapid and almost quantitative conversion into 4-substituted 1,2,3-benzotriazines (8, R = Me, OMe, Ph). 1,2,3-Benzotriazine (8, R = H) was prepared similarly, and for the first time, by carefully controlled oxidation of either 1- or 2-aminoindazole (6, 7, R = H). These remarkable ring expansion reactions, which apparently proceed via the formation of intermediate nitrenes, appear to be a direct and logical extension of original work by Bamberger and Goldberger in 1898 on the oxidative ring expansion of... 

Hydrolysis of condensed 1,2,3-triazines results in cleavage of the heterocycUc ring and is in many respects an unexceptional and fully predictable type of reaction. The relative ease with which ring fission takes place, and the products formed, depend almost entirely on the nature of the substituents at the 3- and 4-positions and on the reaction conditions employed. Moreover, hydrolysis under basic conditions normally leads to fission of the N,—C4 bond whereas under acidic conditions most 1,2,3-benzotriazine derivatives behave as masked diazonium compounds, and hydrolysis proceeds with fission of the Nj— N3 bond and transient formation of a diazonium compound, from which the observed products are ultimately derived. Hydrolysis of certain derivatives probably also involves covalent hydration as the key step. 

Treatment of 3-aryl-4-imino-3,4-dihydro-l,2,3-benzotriazines (67) with sodium ethoxide and methyl iodide results in formation of a mixture of the isomeric methylated triazenes 130 and 131 by base-catalyzed... 

Results available from studies of the photochemical decomposition of benzotriazinones indicate that formation of the reactive species 146 during thermolysis of 10 is a reasonable postulate. Simple 3-alkyl-1,2,3-benzotriazin-4(3/f)-ones (10, R = alkyl) are apparently inert to photo-... 

Two major fragmentation pathways have been observed in the mass spectrum of l,2,3-benzotriazin-4-one (10, R = H), and these are outlined in Scheme 1. The primary mode of cleavage (Path a) involves loss of nitrogen and formation of the y3-lactam (179), which undergoes further fragmentation as shown. Alternatively, loss of HCNO or HNj (Path b) leads to a diazonium ion or acylium radical ion which then decomposes to CjH by loss of nitrogen or carbon monoxide. The mass... 

Most known monocyclic 1,2,3-triazines and 1,2,3-benzotriazines are stable at room temperature. No detailed study of the stability of monocyclic 1,2,3-triazines towards water, aqueous acids or bases has been published, but one can assume from the reaction conditions used in the preparation of monocyclic 1,2,3-triazines, by oxidation of (V-aminopyrazoIes, that they are stable to water, aqueous acids or bases at room temperature, at least for a short time. Treatment of triaryl-1,2,3-triazines with aqueous hydrochloric acid at higher temperatures leads to hydrolysis of the ring and formation of 1,3-dicarbonyl compounds (Scheme 3) (60TL(13)19,76UP21800). 

Only a few examples of the formation of 1,2,4-triazines by this fragment combination have been published, all cases being 1,2,4-benzotriazine syntheses. 2-Nitroaniline reacts with cyanamides to give 2-nitrophenylguanidines (601) which cyclize under basic conditions to 3-amino-l,2,4-benzotriazine 1-oxides (602) <78HC(33)189, p.699). With benzoyl isothiocyanate it affords Ar-(2-nitrophenyl)-N -benzoylthiourea (603), which cyclizes to l,2,4-benzotriazine-3-thione 1-oxide (604) (80MI21900).. 

The reaction of benzofurazan oxide (605) with amines has been studied by Haddadin et al. (79T681). With diethylamine, beside other products, 3-methyl-l,2,4-benzotriazine (606) and its 4-oxide (607) were isolated, the production of which was explained by the intermediate formation of (608) and (609). 

The six-atom cyclization is commonly encountered in 1,2,4-benzotriazine synthesis. In most cases the reactions are real [6 + 0] atom fragment methods since, although reactive intermediates may be involved, the precursors usually have all six atoms present in the molecule. As with the monocyclic compounds, it is usually a C—N bond which is formed in the cyclization but some syntheses take place with N—N bond formation. 

Cyclization of the 2-acylaminoazobenzenes (729) leads to 2-aryI-l,2,4-benzotriazinium salts (730) (74GEP2241259). When the azo compound (731) was heated without a solvent to 200°C 3-amino-l,2,4-benzotriazine (732) was isolated (27CB2598) this involves N(l)—C(8a) [N(l)—C(6)] bond formation, unusual in 1,2,4-benzotriazine syntheses. 

The reaction of A -arylbenzamidoximes (245) with nitrile oxides in refluxing toluene has been reported to lead mainly to benzotriazines (247), the formation of which has been explained285 by postulating the occurrence of an unusual [3,5]-rearrangement of the non-isolated 1 1 adduct (246) (see Scheme 57). 

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