4- Amino-1,2,3-benzotriazines

Benzotriazinium betaines (13) and (26) are stable toward acids. They are slightly basic compounds and form salts with acids which are easily hydrolyzed. The corresponding 1-oxides (33) behave similarly, being, for instance, souble in concentrated hydrochloric acid from which they are reprecipitated on dilution with water (27JCS323). 4-Amino-1,2,3-benzotriazines (38) and 4-imino-l,2,3-benzotriazines (39) behave as masked diazonium compounds (40) and the products of acidic treatment of these compounds are best explained as reaction products of the diazonium salts (78HC(33)78). Treatment of 1,2,3-benzotriazine... 

Benzotriazine, 6-amino-3-methyl-4-oxodihydro-azo pigments from, 1, 334... 

The condensation of 3-amino-1,2,4-benzotriazine 1-oxides 29 with a-halo-carbonyl compounds results in imidazo[2,l-c]-l,2,4-benzotiiazine 1-oxides 30 (82JHC61, 86MI). 

The treatment of 3-amino-1,2,4-triazine 2-oxides 1 or 3-amino-1,2,4-benzotri-azine 1-oxides 29 with nitrous acid proceeds as a diazotization reaction, but the diazo compounds have never been isolated owing to the easy displacement of the di-azo group with nucleophiles. Thus the reaction of 3-amino-1,2,4-triazine 2-oxides 1 with sodium nitrite in hydrochloric or hydrobromic acids leads to the corresponding 3-halogen-1,2,4-tiiazine 2-oxides 119 or 3-bromo-l,2,4-benzotriazine 1-oxides 120 (77JOC546, 82JOC3886). 

A few interesting organic molecules may possess the ability to release hydroxyl radical under physiological conditions. The most extensively studied of these is 3-amino-l,2,4-benzotriazine 1,4-dioxide (tirapazamine, 95, Scheme 8.32). Tirapazamine is a bioreductively activated DNA-damaging agent that selectively kills the oxygen-poor (hypoxic) cells found in solid tumors. The biological activity of... 

The bifunctional electrophilic reagent iV-chlorocarbonylisocyanate reacted with 3-amino-5,9,9-trimethyl-5,6,7,8-tetrahydro-5,8-methano-l,2,4-benzotriazine 41 followed by treatment with Et3N to give [l,3,5]triazine[l,2- ][l,2,4]-benzotriazine-2,4(377)-dione 21 (Equation 3) <1998JHC293>. 

E Atherton, JL Holder, MMeldal, RC Sheppard, RM Valerio. 3,4-Dihydro-4-oxo-l,2,3-benzotriazin-3-yl esters of fluorenylmethoxycarbonyl amino acids as self-indicating reagents for solid phase peptide synthesis. J Chem Soc Perkin Trans 1 2887, 1988. 

MH Jakobsen, O Buchardt, T Engdahl, A Holm. A new facile one-pot preparation of pentafluorophenyl (Pfp) and 3,4-dihydro-4-oxo-l,2,3-benzotriazine-3-yl (Dhbt) esters of Fmoc amino acids, (acid chlorides). Tetrahedron Lett 32, 6199, 1991. 

Methy Isulfonyl) methyl)- ,2,3-benzotriazin-4(3/J-one, see Azinphos-methvl Methyl sulfuric acid, see Dimethyl sulfate 2-Methylthio-4-amino-6-isopropylamino-s-triazine, see Prometrvn... 

As mentioned in Section II,D,l,a, the presence of a r-butyl or phenyl group at position 5 of the 1,2,4-triazine ring does not prevent addition of the amide ion to that position. Therefore, it becomes of interest to investigate whether in the amino-dehalogenation of two annelated 3-chloro-l,2,4-triazines, i.e., 3-chloro-l,2,4-benzotriazine (123) and 3-chlorophenanthro[9,10-e]l,2,4-triazine (125), using potassium amide/liquid ammonia, the Sn(ANRORC) process would be involved. Both compounds... 

Treatment of 36 with nitrous acid in dilute acetic acid gives a mixture of anthranilazide (37) and 3-amino-1,2,3-benzotriazin-4(3/f)-one (10, R = NH2). When the same reaction is carried out in dilute hydrochloric acid, the sole product formed initially with one mole equivalent of nitrous acid is 10, R = NHj, but this readily reacts further to give 10, R = Diazotization of acetophenone anthranylhydrazone followed by mild acid hydrolysis is a superior route to 10, R = NHj, and gives a much purer product. l,2,3-Benzotriazine-4(3/0-thione (39, R = H) and the 3-substituted derivatives (39) are readily available by diazotization of thioanthranilamide (38, R = H) and its derivatives. ... 

For many years it was believed that anthraniionitrile did not react with either ammonia or hydrazine to give the corresponding amidines, and consequently, 4-amino- (56, R = H) and 4-hydrazino-1,2,3-benzotriazine (56, R = NHj) were first prepared by reaction of 4-methylthio-l,2,3-benzotriazine with ammonia and hydrazine, respectively. In general, alkylamines react readily with 1,2,3-benzotriazine-4(3 -thione (39, R = H) to give the corresponding 4-amino derivatives... 

The reactions of 3-amino-l,2,3-benzotriazin-4(3//)-one and a number of its derivatives (lOla-g) under both acidic and basic media have been investigated in some detail by Gibson and Green. Earlier work by Heller and his colleagues had apparently established that treatment of lOla-e with hot aqueous sodium hydroxide solution gave o-azido-benzoic acid (102), and Gibson and Green showed that lOlf behaved similarly. The benzylidenamino derivative 10 Ig, however, was reported by Heller to yield benzaldehyde o-carboxyphenylhydrazone (103) under basic conditions, and benzimidazolone (104) under acidic conditions. 

In contrast to the above situation with respect to oxidation of the ring nitrogen atoms of 1,2,3-triazines, oxidation of derivatives of 3-amino-l,2,3-benzotriazin-4-(3/0-one (101a) has proved to be of considerable interest and has been investigated in some detail by Rees and his colleagues. Treatment of 101a with lead tetraacetate at 80° has been shown to give benzyne in very low yield, but at room... 

Diazotization of 2-amino-N-cyanomethylbenzamide (79) and subsequent treatment with sodium azide yields 3-cyanomethyl-l,23-benzotriazin-4-one 80 <99H1295>. 

Substituenten in 2-Stellung bestimmen bei der Blei (IV)-acetat-Oxidation von 1-Amino-benz-imidazolen, welche Produkte entstehen. Das intermediar gebildete Nitren dimerisiert entweder zum Tetrazen oder lagert sich zura 1,2,4-Benzotriazin um. Nur heim unsubstituierten 1-Amino-benzimidazol selbst lauft die Oxidation weiter und das Tetrazen wird zu 1-Acetyl-benzimidazol gespalten534 z.B. ... 

Mit dem Dinatriumsalz von Cyanamid wird 3-Amino-1,2,4-benzotriazin-l,4-bis-oxid (81 %)320 gebildet, mit Cyan-acetamid hingegen 2-Aminocarbony -l-hydroxy-benzimidazol-3-oxid (78%)321 [analog reagieren 1-Nitro-alkane322-324 und (3-Oxo-alkyl)-sulfone]325 ... 

Amino-asym-benzotriozine or 3-lmino-2,3(or 3,4)-di hydra- l,2,4-benzotriazine(origi-... 

CH=CH C-N=ONH2 CH—CH-CMST-CiNH Yel ndls, mp 207°. Sol in hot ale and less in ether. May be prepd by oxidation of 3-amino-l>2-dihydro-l)2f4"benzotriazine with K ferri-cyanide(Re 2 or by the mediod described in Ref 3 The compd was investigated by Merck Co(Ref 4). It is described here because it has fairly high N content... 

Quinazolino[3,2-c]l,2,3-benzotriazin-8(7//)-imine (611) was prepared from 4-amino-2-(2-aminophenyl)quinazoline (609) by diazotization, followed by basilication of the resulting diazonium salt (610). The isomeric... 

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... 

A-Aminopyridones can be oxidized to nitrenes. Thus, 3-amino-1,2,3-benzotriazin-4-ones (977) with lead tetraacetate lead to an intermediate nitrene (978), which can lose one or two molecules of nitrogen. 

---