254-87-5

Usage

Uses

Used in Chemical Production Industry:
1,2,4-Benzotriazene is used as a chemical intermediate for the production of dyes and pigments, contributing to the coloration and enhancement of various materials. Its role in this industry is crucial for the development of a wide range of colorants used in different applications, including textiles, plastics, and printing inks.
However, due to its hazardous nature, the use of 1,2,4-Benzotriazene in chemical production must be carefully managed with stringent safety protocols to prevent exposure and protect the health of workers and the environment. This includes implementing appropriate containment measures, personal protective equipment, and disposal methods to minimize the risk of carcinogenic and mutagenic effects associated with 1,2,4-Benzotriazene.

Upstream product

• 64241-51-6 benzo[e][1,2,4]triazine-3-carboxylic acid 
• 60702-35-4 N-Formyl-N'-(o-nitrophenyl)hydrazine 
• 1885-34-3 N,N'-diphenylformazan 
• 6299-89-4 N-Formyl-N'-(o-aminophenyl)hydrazine 
• 6165-66-8 1,5-diphenyl-formazan-3-carboxylic acid ethyl ester 
• 75122-01-9 3-methylsulfanyl-1,2,4-benzotriazine 
• 67692-91-5 3-chloro-1,2,4-benzotriazine 1-oxide 
• 20028-80-2 SR 4330 
• 5424-06-6 3-amino-1,2,4-benzotriazine 1-oxide 
• 51661-19-9 1,2-bis(2-nitrophenoxy)ethane 
• 612-28-2 2-nitro-N-methylaniline 
• 114098-35-0 amino-(2-nitro-phenylhydrazono)-acetic acid ethyl ester 
• 110181-37-8 bromo-(2-nitro-phenylhydrazono)-acetic acid ethyl ester 
• 119-66-4 2-nitrobenzenediazonium chloride 

Downstream Products

• 95-14-7 1,2,3-Benzotriazole 
• 59323-44-3 benzo[e][1,2,4]triazine-1-oxide 

Relevant academic research and scientific papers

3-Substituted Benzo[ e][1,2,4]triazines: Synthesis and Electronic Effects of the C(3) Substituent

A series of 19 structurally diverse C(3)-substituted derivatives of benzo[e][1,2,4]triazine were synthesized from 3-chloro- (1c) and 3-iodobenzo[e][1,2,4]triazine (1d) obtained in three steps from 2-nitroaniline in 37-55% yields. Nucleophilic aromatic substitution and metal-catalyzed (Pd, Cu) reactions led to functional derivatives that include alkyl (C5H11), (het)aryl (Ph, 2-thienyl, ferrocenyl), ArCC, amine (NHPh and morpholine), PO(OEt)2, sulfanyl (SBu-t), alkoxide (OEt, OMe), and CN. The synthesis of C(3)-CF3 derivative 1g via the Ruppert reaction with 1d and its 1-oxide analogue 2d led to the substitution followed by formal addition of HCF3 to the C?N bond. Pd-catalyzed carbonylation reactions of 1d and 2d did not give the corresponding C(3)-carboxylic acids. Therefore, acid 1f was obtained through hydrolysis of the CN. The substituent effect on the electronic structure of the benzo[e][1,2,4]triazine ring was investigated by spectroscopic methods (UV-vis and NMR) augmented with density functional theory calculations. Results show significant effect of the C(3) substituent on the (1) transition energy and good correlation of the 1H NMR chemical shift with the substituent constant σp. Molecular and crystal structures of six derivatives were established with the single-crystal X-ray diffraction method, and the substituent impact on the molecular geometry was investigated.

Isotopic labeling experiments that elucidate the mechanism of DNA strand cleavage by the hypoxia-selective antitumor agent 1,2,4-benzotriazine 1,4-Di- N -oxide

The 1,2,4-benzotriazine 1,4-dioxides are an important class of potential anticancer drugs that selectively kill the low-oxygen (hypoxic) cells found in solid tumors. These compounds undergo intracellular one-electron enzymatic reduction to yield an oxygen-sensitive drug radical intermediate that partitions forward, under hypoxic conditions, to generate a highly reactive secondary radical that causes cell killing DNA damage. Here, we characterized bioreductively activated, hypoxia-selective DNA-strand cleavage by 1,2,4-benzotriazine 1,4-dioxide. We found that one-electron enzymatic activation of 1,2,4-benzotriazine 1,4-dioxide under hypoxic conditions in the presence of the deuterium atom donor methanol-d4 produced nondeuterated mono-N-oxide metabolites. This and the results of other isotopic labeling studies provided evidence against the generation of atom-abstracting drug radical intermediates and are consistent with a DNA-damage mechanism involving the release of hydroxyl radical from enzymatically activated 1,2,4-benzotriazine 1,4-dioxides.

Complete 1H, 13C and 15N NMR assignment of tirapazamine and related 1,2,4-benzotriazine N-oxides

1H, 13C and 15N NMR measurements (1D and 2D including 1H-15N gs-HMBC) have been carried out on 3-amino-1, 2,4-benzotriazine and a series of N-oxides and complete assignments established. N-Oxidation at any position resulted in large upfield shifts of the corresponding N-1 and N-2 resonances and downfield shifts for N-4 with the exception of the 3-amino-1,2,4-benzotriazine 1-oxide in which a small upfield shift of N-4 was observed. Density functional GIAO calculations of the 15N and 13C chemical shifts [B3LYP/6-31G(d)//B3LYP/6- 311+G(2d,p)] gave good agreement with experimental values confirming the assignments. The combination of 13C and 15N NMR provides an unambiguous method for assigning the 1H and 13C resonances of N-oxides of 1,2,4-benzotriazines. Copyright

Flash vacuum pyrolysis (F.V.P.) of 1,2,4-benzotriazine derivatives

Flash vacuum pyrolysis of 3-methylsulfanyl-1,2,4-benzotriazine N-oxide, 3-methylsulfanyl-1,2,4-benzotriazine, and 3-phenyl-1,2,4-benzotriazine are described. The N-oxide derivative underwent deoxygenation between 500 and 600°C, whereas at higher temperatures both methylsulfanyl compounds, besides yielding the same products, also gave benzimidazole formed by an independent mechanism. Transformation of these derivatives between 600 and 750°C led to formation of a complex reaction mixture indicating the radical nature of the processes. The phenyl substituted derivative was studied between 575 and 650°C and afforded benzonitrile and traces of biphenylene.

Electrochemical reduction of o-nitrophenylhydrazides into 1,2,4-benzotriazines.

Phenylhydroxylamines, obtained in aqueous medium, by electroreduction of o-nitrophenylhydrazides (o-NO2-C6H4-NH-NHCOR), undergo a disproportionation reaction leading finally to the corresponding o-amino compound; the latter partially rearranges into an o-amidophenylhydrazine (o-RCONH-C6H4-NH-NH2).In a basic media, the disproportionation reaction is concurrent with a ring closure of the intermediate hydroxylamine giving rise to a 1,2,4-benzotriazine.The latter is also obtained by anodic oxidation of the amine, mixed with anilide resulting from the hydrazine oxidation.Electroreduction, immediately followed by an anodic oxidation gives rise to about 50percent yield in the expected triazine.In an acidic media, disproportionation is faster, but the resulting amine undergoes a ring closure reaction into dihydrobenzotriazine when R = H or CH3.Subsequent oxidation of the latter gives rise to 75percent yield of the triazine, mixed with N-aminobenzimidazole resulting from the hydrazine.When R = Ph, the amine is stable but only very poor yields of triazine are obtained by anodic oxidation; the major evolution is probably the formation of an unstable benzoylbenzotriazole.Key words: cyclic voltammetry, controlled potential reduction and oxidation, 1,2,4-benzotriazine, 1-amino-2-alkylbenzimidazoles, organic electrosynthesis.

Process for preparing 1,2,4-benzotriazine oxides

A method of using 1,2,4-benzotriazine oxides, some of which are novel compounds, as radiosensitizers and selective cytotoxic agents is disclosed. These compounds are shown to specifically radiosensitize hypoxic tumor cells. Some are additionally disclosed to be useful as specific cytotoxic agents for these cells. They also show an unexpected ability to radiosensitize aerobic cells following or preceding a hypoxic incubation of the cells with the drug. This provides a basis for selective radiosensitization of tumors compared to normal cells. A novel method for preparing the 1,2,4-benzotriazine oxides is also disclosed.

OXIDES OF 3-METHYL-1,2,4-BENZOTRIAZINE

The previously prepared 3-methyl-1,2,4-benzotriazine oxide is shown to be the 4-oxide 5.Synthesis and structores of other isomeric and related oxides are described.A modification of a previously described synthesis of 1,2,4-benzotriazines produces purer products in higher yields.