Benzotriazines and Other Condensed 1,2,3-Triazines

There are relatively few methods available for the preparation of condensed 1,2,3-triazines. By far the most commonly employed procedure is diazotization of a suitably ortho-substituted aniline (4) or amino-substituted heterocycle of the type 5, and examination of the different X substituents which have been used successfully in this synthesis reveals 

Neunhoffer, H.-D. Votter, and M. Gais-Muttercr, Tetrahedron Lett., 219 (1973). 

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 

Alternative procedures for the preparation of 4-alkyl- and 4-aryl-1,2,3-benzotriazines have also been investigated by Rees. Thus, the diazoazide (11) undergoes smooth decomposition in refluxing benzene to give 4-methyl-1,2,3-benzotriazine (8, R = Me) in 70% )deld. Oxidation of the o-aminohydrazones (12, R = Me, Ph,p-MeOCsH4) with lead tetraacetate also gives the corresponding triazines (8) in moderate yield. 

Direct oxidation of condensed 1,2,3-triazines to N-oxides has not been studied in detail, and the feasibility of such methods has been rigorously established in only a single instance (see Section II, C, 2). With the exception of the 1,2,3-triazinium betaine N(l)-oxides, which are discussed separately, all the remaining known 1,2,3-triazine N-oxides, which are 3-oxides, have been prepared by diazotization of appropriate precursors. Thus, diazotization of o-aminophenylketoximes (14, R = Me,. Ph) gives the corresponding 4-substituted 1,2,3-benzotriazine 3-oxides (15) directly. Formulation of these products as triazine N- 

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X-ray crystallographic data are also available for 1,2,3-benzotriazines 3 and 12 15 and other condensed 1,2,3-triazines 16-19. Since a structure determination of the unsubstituted or alkyl-substituted 1,2,3-benzotriazines is not yet available, comparison with the monocyclic compounds is not possible. 

Hydrolytic cleavage of condensed 1,2,3-triazine derivatives is normally a straightforward, high-jneld process which results in production of one or other of several distinct types of product. 3-Alkyl- and 3-aryl-3,4-dihydro-l,2,3-benzotriazines, for example, undergo facile hydrolysis in concentrated hydrochloric acid to give, via the diazonium compound, A(-alkyl- and W-aryl-substituted o-chlorobenzylamines (100, R = Cl). If the reaction is carried out in water or in dilute mineral acid, the corresponding -alkyl and iV-aryl-substituted o-hydroxybenzylamines (100, R = OH) are obtained. 

As mentioned above, condensed 1,2,3-triazine derivatives can be arylated by treatment with nitro-activated aryl halides. The only other report of direct arylation of the 1,2,3-triazine system is due to McKillop and Kobylecki, who studied the reaction of l,2,3-benzotriazin-4-one (10, R = H) with diaryliodonium salts in the presence of base. Treatment of 10, R = H, with diphenyl- and di-p-bromophenyliodonium chloride results in exclusive arylation at N2 and gives the corresponding triazinium betaines (77, R = Ph, p-BrCjH4) in good yield. When di-p-tolyliodonium chloride is used, a mixture of the Nj-, Nj-, and 0-arylated... 

For a number of condensed 1,2,3-triazines, it has been shown that an equilibrium can exist between the cyclic structure and an open-chain form.39-41 Depending on the substituents R1 and R2 and the solvent, 1,2,3-benzotriazines are in equilibrium with the open-chain triazene form.39-41 Since 1,2,3-benzotriazines, and the other fused 1,2,3-triazines which show reversible ring opening, are not aromatic systems, this problem will not be discussed in detail here. 

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