Benzo triazin-4 -ones

Condensed 4-halo-1,2,3-triazines are a virtually unknown class of compounds and are apparently very unstable. Reaction of 1,2,3-benzo-triazin-4-one (10, R = H) with a mixture of phosphorus oxychloride and phosphorus pentachloride, for example, results in formation of o-chlorobenzonitrile, presumably via formation and then decomposition of the 4-chlorotriazine (137) to give the diazonium salt (138), subsequent... 

Amino- (459) and 3-amino-quinazolin-2-ones (460) (75JCS(Pl)3l), as well as 1-amino- and 2-amino-indazoles (92AHC(53)85) can be oxidized to 1,2,3-benzotriazines. C-Amino compounds can also give triazines oxidation of 3-aminoindazole (461) with hydrogen peroxide forms 1,2,3-benzo-triazin-4-one (462) <1899LA(305)289). 

The reaction of anthranilic acid amide with nitrous acid yields 1,2,3-benzo-triazin-4"One, from which the insecticide azinphos-methyl Bayer) is made with formaldehyde and 0,0-dimethyldithiophosphoric acid. 

Diazotization of anthranilamide and its derivatives is the most common and widely exploited reaction for the preparation of 1,2,3-benzo-triazine derivatives. The reasons for this are 3-fold (i) many nuclear substituted anthranilic acid derivatives are readily available (ii) the diazotization reactions generally proceed smoothly and in high yield, and the product triazinones are usually very stable and easily handled and (iii) many 3-substituted l,2,3-benzotriazin-4(3i/)-ones have been found to possess a wide range of pronounced pharmacological activity, while others undergo a number of very interesting chemical transformations, and hence a very large number of these compounds have been prepared. 

Anderson RF, ShindeSS, Elay MP, GamageSA, Denny WA (2003b) Activation of 3-amino-1,2,4-benzo-triazine 1,4-dioxide antitumor agents to oxidizing species following their one-electron reduction. J Am Chem Soc 125 748-756... 

Fluorophenyl)-3H-benzo-l,2,3-triazin- one (XVl) is reported to be twice as effective as chlorphentermine in suppressing appetite in pats. No toxic effects were noted,66... 

If diazomethane is added slowly to an etheral suspension of benzo-l,2,4-triazin-3-one, the 0-methyl derivative (cf. 161) is obtained in good yield, but, if the solid benzotriazinone is added to an etheral solution of diazomethane, approximately 50% of the A -methyl derivative (or, according to a later report, 70% of a mixture of two isomeric iV-methyl derivatives) is formed. These facts have been interpreted to indicate that the benzotriazinone exists as such in the solid state, i.e., as 162, and partially tautomerizes to 161 in solution. Similar results have been reported and similar conclusions drawn for the related 1-oxide 162a. ... 

Benzo-l,2,3-triazin-4-ones with the general structure 6.54 (X = O, S, or H2) are obtained by diazotization of the appropriate aniline derivatives 6.53 (Scheme 6-38). In polar aprotic solvents (e. g., nitrobenzene) the reverse reaction takes place to give the diazonium ion (for an example see Kullick, 1966). Diazotization of 1,8-diamino-naphthalene yields l-i/-naphthol[l,8-cfe]triazine (6.55 Tavs et al., 1967). In concentrated HC1 the triazine ring is opened again. 

The synthetic method indicated in Scheme 6-38 is important for the preparation of heterocyclic analogues of benzo-l,2,3-triazin-4-ones. The cyclization products of... 

Thus oxidation of both 6- and 7-substituted 3-amino-benzo-l,2,3-triazin-4-ones with lead tetraacetate in methanol produced a mixture of p- and m-substituted benzoates, clearly indicating that a symmetrical intermediate, i.e. benzocyclopropenone (166) was formed and underwent ring opening by attack of solvent121 ... 

The first representative of the [l,2,4]triazino[5,6-fc]diazepin-8-ones 583 was obtained by reaction of 6-amino-3-(p-tolyl)[l, 2,4]triazin-5(2//)-thione 581 with 2//-1,3-oxazine-2,6(3//)-dione [85LA(3)640]. The benzo analogue [l,2,4]triazino[5,6-b][l,4]benzodiazepinones 582 were similarly obtained by reaction of 581 with isatoic anhydride. 

Acylhydrazides of anthranilic acid (35, R = NHCOR ) give 3-acylamino-l,2,3-benzotriazin-4(3H)-ones (10, R = NHCOR on treatment with nitrous acid. The triazine hydroxamic acid (40) and its benzo-substituted derivatives are available by diazotization of the corresponding o-aminobenzohydroxamic acids. The pyrido[2,3-e]triazine analog (41) was prepared similarly from 3-aminoisonicotino-hydroxamic acid, but the isomeric 2-aminonicotinohydroxamic acid failed to react under the same conditions to give 42. ... 

Napthlylamine, when reacted with l,2,4-triazin-5-ones in acetic acid, gives benzo[e]indole-2,3-dione in 71 to 81% yields, but both aniline and 1-methylaniline fail to furnish the corresponding isatins. ... 

Similar ring contractions in which the nitrogen-nitrogen bond is cleaved are found in the reductive ring contractions of pyridazines to pyrroles [148, 149], phthalazines to isoindoles [150], 5,6-diphenyl-1,2,4-triazinones to imidazolones [151], benzo-l,2,4-triazines to benzimidazoles [71], benzo-l,2,3-triazinone to indazolone [la, 152], benzo-l,2,3-triazin-3-oxide to indazole [la], benzo-2,3-diazepines to isoquinolines [153], benzo-l-pyrano-[4,3-e ]-as-triazin-3-one to benzopyranoimidazolone [154], and 2-methyl-4,5-dihydropyridazin-3-ones to pyrrolin-2-ones [155]. 

Relatively few reactions of quinoxaline derivatives occur with change of ring size. Isolated examples are noted in the following text. For example, ring contraction to benzimidazole derivatives occurs when 2,3-diphenylquinoxaline (Chapter XV) or 2-halogenoquinoxalines (Chapter X) are treated with potassium amide in liquid ammonia and quinoxalin-2-one is treated with hydrazine (Chapter VX It is also found that oxidation of l-aminoquinoxalin-2-ones with lead tetraacetate give benzo-1,2,4-triazines (Scheme 6) (Chapter V). 

Bicyclic 5-6 Systems, One Ring Junction N Four Extra Heteroatoms 2 2 Table 1 Proton NMR shifts of some [l,2,4]triazolo[3,4-c]benzo[l,2,4]triazines in DMSO-d. ... 

When reacting with l,2,4-triazin-5-ones 34, benzo-annelated crown ethers 40 and their open-chain analogs, the podands 42, behave like phenol ethers, thus yielding C-adducts 41 and 43 (Scheme 24) <2001H(55)2349>. 

In a similar fashion, compounds 34 react with benzo-annelated crown ethers, which contain the phenol moiety, to form adducts 41, which can be transformed into Sn products through elimination of aldehyde (see also Section 9.02.5.7.l(i)). Indeed, thermolysis of the a -adducts 41 affords l,2,4-triazin-5-ones 113 (Scheme 60) <2001H(55)2349>. Yields of 113 are poor, but can be improved when the reaction is carried out in an argon atmosphere <2001H(55)2349>. 

The construction of six-membered rings with three nitrogen atoms on the basis of isatoic anhydrides has only been described for 1,2,3-benzotriazines. This method for the synthesis of the latter includes reaction of the anhydrides with primary amines and subsequent diazotization of the obtained amino amides, which dictates the use of initial isatoic anhydrides not containing substituents at the nitrogen atom. Thus, the action of sodium nitrite and hydrochloric acid on the amino amides 161, formed from the anhydrides 1, 10, 162 and imidazolylalkylamines, leads to diazotization and cyclization with the formation of derivatives 208 of benzo-l,2,3-triazin-4-ones (yields 36-85%) [96, 126],... 

The cyclization kinetics of 11 model l-[2-(methoxycarbonyl)phenyl]-3-(2-substitut-ed phenyl)triazenes (177) have been examined in aqueous methanolic buffer solutions at various pH values. 3-(2-Substituted phenyl)benzo[fi ][l,2,3]triazin-4(3 f)-ones (178) were identified as the cyclization products. The log fcobs vs pH plot was linear with a slope of unity. The assumed and confirmed Bac2 mechanism involving specific base catalysis begins by deprotonation of the triazene giving rise to the conjugate base, continues with formation of a tetrahedral intermediate, and ends with elimination of the methanolate ion (Scheme 32). Desilylation with methanolic HCl of the substituted anilide (179), a compound formed by a Ugi reaction, led to a facile intramolecular conversion to an ester (180). This reaction was the key step in a... 

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