L,2,3-Benzotriazin-4 -ones

There are two general ring syntheses available for the preparation of 3-substituted l,2,3-benzotriazin-4(3//)-ones, namely, (i) diazotization of anthranilamide and its derivatives and (ii) cyclization of 1-alkyl- or 1-aryl-3-(o-carbalkoxy)triazenes, and both reactions have been studied in considerable detail. 3-Substituted l,2,3-benzotriazin-4(3//)-ones have also been obtained by alkylation and acylation of l,2,3-benzotriazin-4-one these last reactions are discussed separately (see Section II, C, 3). 

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... 

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... 

Considerable interest has developed during the last ten years in the potential utility of condensed 1,2,3-triazine derivatives as medicinals, although the first indication that these compounds might be useful appears to be the report by Woolley and Shaw in 1951 that the 2-azadenine derivative (183) inhibited hypoxanthine activity in Lactobacillus brevis. l,2,3-Benzotriazin-4-one (10, R = H) is reported... 

Oxazines and thiazines are unstable with respect to ring-opened isomers (cf. 30—>31). l,2,3-Benzotriazin-4-ones on protonation undergo ring-chain tautomerism to yield diazonium ions (Scheme 8 see CHEC 2.18). 

Benzotriazine (20) shows the following IR bands vmax(KBr) = 1473, 1383, 877, 800 and 750 cm-1 (75JCS(Pl)3l). In the IR spectra of l,2,3-benzotriazin-4-ones an intense band between 1700 and 1667 cm-1 is observed, showing that the hydroxy tautomer (lOd) can be excluded. Similarly, it was shown that in l,2,3-benzotriazine-4-thiones (22) the thione form predominates in the solid state. The IR spectra of 4-anilino-l,2,3-benzotriazines (23) show a strong absorption band at 1145 10 cm-1 which is absent in the 3-aryl-4-imino isomers (24) and presents a useful means of distinction between these isomers (70JCS(C)765). 

Amino-l,2,3-benzotriazin-4-ones (35) are transformed by acid primarily into the diazonium ions (36) which then give anthraniloyl azides (37) (65T2191, 27JPR(116)9, 25JPRU 11)36). 

No products could be identified when 3-alkyl- or 3-aryl-4-methylene-3,4-dihydro-l,2,3-benzotriazines were refluxed in ethanol or p-xylene (75CJC3714). Flash vacuum pyrolysis of 3-adamantyl-l,2,3-benzotriazin-4-one (79) led to the isolation of 1-adamantylbenzazet-2(l//)-one (80) (73JCS(P1)868>. In most other cases the isolation of the benzazetone failed. When l,2,3-benzotriazin-4-one (21) is heated in diethylene glycol dimethyl ether, quin-... 

Thermal decomposition of 3-arylidenamino- (91) and 3-imidoyl-l,2,3-benzotriazin-4-ones (93) in solution gives 2-aryl- (92) and 2,3-diaryl-quinazolin-4( 177)-ones (94) respectively (80JCS(Pl)633,75S187,75S709). In the latter decomposition phenanthridinones (95) are also formed in minor yields. Mechanisms to account for the isolated products were discussed. 3 -Amino-l,2,3-benzotriazin-4-ones (96) in boiling 1-methylnaphthalene yield in all cases... 

The photolysis of l,2,3-benzotriazine-4-ones has been carefully examined by Ege and his group. 3-Unsubstituted and 3-alkyl-l,2,3-benzotriazin-4-ones seem to be stable towards irradiation with UV light. 3-Aryl-l,2,3-benzotriazin-4-ones (84) lose nitrogen and form benzazetinones (109) which could not be isolated but were detected spectroscopically (76LA946, 78HC(33)58>. 

The UV spectrum of l,2,3-benzotriazin-4-one (10, R = H) consists of two maxima at 223 nm (log e = 3.28) and 278 nm (log e = 2.77)162 and the spectra of a wide variety of 3-alkyl derivatives have been found to be closely similar, with maxima in the ranges 226-244 nm (log e = 4.33-4.49) and 284-289 nm (log e = 3.71-4.03), although only the longer wavelength absorption had been quoted for some compounds. The spectra of the 3-aryl derivatives are also similar to that of 10, R = H,88.89 tjUt significant substituent effects have been noted which depend on the position of the substituent (Me, Ph, MeO, MeCONH, Cl, N02) in the 3-aryl group.88 Thus, relative to 10, R = Ph, the spectra of the o-substituted phenyl derivatives show a strong hypsochromic shift and those of the p-substituted phenyl derivatives show a weak bathochromic shift there is, however, virtually no substituent effect for the m-substituted phenyl derivatives. These effects are almost identical to those found in substituted benzanilides. 

This type of isomerization is much more common in carbonyl-containing rings. A well-known example is the generation of cyclobutadiene by photolysis of pyran-2-one with the loss of CO2. l-Methyl-2-pyridone 24 (XY = MeNC=0, Z = CH) gives 25 (XY = MeNC=0, Z = CH) l,3-oxazin-6-ones 24 (XY = 0C=0, Z = N) form the corresponding bicycles, which can eliminate CO2, and the l,2,3-benzotriazin-4-ones similarly give the corresponding benzazetones. 

Other reactions of /V-amino compounds. Al-Aminopyridones can be oxidized to nitrenes. Thus, 3-amino-l,2,3-benzotriazin-4-ones 1021 with lead tetraacetate leads to a nitrene 1022, which can lose one or two molecules of nitrogen (Scheme 117). 

Convenient procedures are based on the cyclization of the suitably ortho-substituted phenyltriazenes . For example, l,2,3-benzotriazin-4-one 446 was obtained from 3-(carbamoylmethyl)-l-(2-alkoxycarbonyl) phenyltriazenes 445 by heating in a minimum volume of ethanol (Scheme 231) <1996JOC210>. A similar cyclization of 447 under acidic conditions affords the benzotriazine 448 (Scheme 232) <2004JC038>. 

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