5-Aminobenzotriazole

Oxidation of 1 -aminobenzotriazole also yields benzyne under mild conditions. An oxidized intermediate decomposes with loss of two molecules of nitrogen. ... 

The l-aminobenzotriazoles are desirable as benzyne precursors. The dianion of N-boc-1-aminobenzotriazole 34 reacts to introduce electrophiles at the 7 position to give 35 in excellent yields <96TL5615>. Pyrrolo[l,2-c][l,2,3]triazoles 37 are formed by trapping... 

Mechanism-based inactivation of cytochrome P450 2B1 by N-benzyl-1-aminobenzotriazole. Chemical Research in Toxicology, 10 (5), 600-608. 

Ortiz de Montellano, P.R. and Mathews, J.M. (1981) Autocatalytic alkylation of the cytochrome P-450 prosthetic haem group by 1-aminobenzotriazole. Isolation of an NN-bridged benzyne-protoporphyrin IX adduct. Biochemical Journal, 195 (3), 761-764. 

Methods such as the pyrolysis of (106), that do not require strongly basic conditions, have l en used to generate arynes in bulk for preparative purposes, and another, even better, method is oxidation of 1-aminobenzotriazole (107) with lead tetraacetate ... 

Oxidation of 1-aminobenzotriazole (283) among other products results in the formation of bistriazolo compound 284. This reaction involves a benzene intermediate and illustrates an example wherein IBD behaves differently than lead tetra-acetate, which in this case gives biphenylene [80JCR(S)303] (Scheme 71). 

The addition of benzyne to Cgg leads to the formation of [2+2] qfcloadducts [330-332]. The in situ generation of benzyne can be achieved by diazotization of anthraniKc acid at room temperature with isoamyl nitrite, by diazotization of the potassium salt of anfhranilic acid in the presence of 18-crown-6, or by the oxidation of 1-aminobenzotriazole with lead tetraacetate (Scheme 4.54). Adduct formation occurs in the 1,2-position, leading to the corresponding ring-closed structure. 

Few reports describe reactions of substituents at the benzene ring of benzotriazoles. The facile deprotonation of the methyl group in N-Boc-7-methyl-1-aminobenzotriazole (403) with butyllithium followed by reactions with electrophiles gives substituted products (404) (Scheme 78). The electrophile can be an alkyl halide, an aldehyde or a ketone, and the Boc group is removed by brief exposure to CF3CO2H in CH2CI2 <93TL6935>. 1-Acetylbenzotriazole (405) is hydrolyzed to form 3-(177-5-hydroxybenzotriazol-6-yl)propionic acid (406), which is then converted (Scheme 79) to... 

Aminobenzotriazoles can be synthesized by two methods (i) direct amination of benzotriazole. This method is simple, however, all possible isomers are formed <86JOC979> (ii) Cyclization of 2-hydrazinobenzenediazonium salts. Reductive cyclization of 2-azobenzenediazoniums (851) gives compounds (852) (Equation (88)). The diazotization of protected 2-hydrazino-anilines (853) followed by hydrolysis allows the preparation of 1-aminobenzotriazoles (854) (Equation (89)). 

Diels-Alder reactions of oxazoles afford useful syntheses of pyridines (Scheme 53) (74AHC( 17)99). A study of the effect of substituents on the Diels-Alder reactivity of oxazoles has indicated that rates decrease with the following substituents alkoxy > alkyl > acyl >> phenyl. The failure of 2- and 5-phenyl-substituted oxazoles to react with heterodienophiles is probably due to steric crowding. In certain cases, bicyclic adducts of type (359) have been isolated and even studied by an X-ray method (87BCJ432) they can also decompose to yield furans (Scheme 54). With benzyne, generated at 0°C from 1-aminobenzotriazole and lead tetraacetate under dilute conditions, oxazoles form cycloadducts (e.g. 360) in essentially quantitative yield (90JOC929). They can be handled at room temperature and are decomposed at elevated temperatures to isobenzofuran. 

Phenanthridinones.1 Benzyne, generated in situ by Pb(OAc)4 oxidation of 1-aminobenzotriazole (l),2 undergoes [4 + 2]cycloaddition to cyclic vinyl isocyanates to form phenanthridinones. 

Oxidative rearrangement of 1-aminobenzotriazole yields the reactive 1,2,3-benzotriazine which reacts with dienophiles to produce quinolines (Scheme 70) <1998CPB332>. 

Figure 16 Mechanism of inhibition of the CYP enzyme inactivator ABT. Abbreviations CYP, cytochrome P450 ABT, 1-aminobenzotriazole.

Reichhart, D., Simon, A., Durst, F., Mathews, J.M., and Ortiz de Montellano, P.R., Autocatalytic inactivation of plant cytochrome P-450 enzymes selective inactivation of cinnamic acid 4-hydroxylase from Helianthus tuberosus by 1-aminobenzotriazole, Arch. Biochem. Biophys., 216, 522-529, 1982. 

Lead tetraacetate oxidation of 3-amino-5-(-butyl-1,2,3-triazolo[4,5-d]pyrimidine (74), as in the case of 1-aminobenzotriazole, leads to a pyrimidyne intermediate which may be trapped using a... 

Benzyne, generated either by oxidation of 1-aminobenzotriazole with lead tetraacetate or by decomposition of benzenediazonium-2-carboxylate, was efficiently trapped by (2) to give 88% of the 1,2-benzisoselenazole (26) however, it was trapped in only 5-10% yield by (1). The series of adducts analogous to (26), prepared from benzyne and substituted benzoselenadiazoles (81JCS(P1)607), occurred via attack of the benzyne at the selenium atom followed by reorganization of the intermediate according to Scheme 6. Benzyne addition to dimethylthiadiazole produced methyl derivatives of quinoline and 1,2-benzisothiazole (82CC299). 

As total inhibitors of the P450 enzyme family, 1-Aminobenzotriazole (Lee and Slattery 1997) and Proadifen (SKF525A) (Lee et al. 1998) are suitable to distinguish from non-cytochrome P450 mediated pathways. 

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