Benzyne 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... 

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. 

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. 

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. 

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). 

With benzyne, formed in situ from 1-aminobenzotriazole, the 2,5-diphenyl-l,3-dithiolium-4-olate (Section III,A,l,d) gives l,3-diphenylbenzo[c]thio-phene in 3b% yield. 

Another method of producing benzyne is from the decomposition of 1-aminobenzotriazole, after it has been oxidised with lead tetraacetate. The oxidation converts the amino group to the nitrene intermediate, and this fragments. Even though there is some doubt over whether nitrenes can exist as true intermediates in these circumstances, suggest a mechanism that utilises their involvement in order to achieve the desired result. 

An interesting reaction is the N-amination by the reagent of benzotriazole (1) to give 1-aminobenzotriazole (2)," a compound of particular interest as a benzyne precursor (.tee Lead tetraacetate, miscellaneous oxidations). 

Campbell and Rees report that benzyne can be generated rapidly and almost quantitatively under mild conditions by oxidation of 1-aminobenzotriazole with lead tetraacetate in benzene. The nitrene (2) presumably is an intermediate. When... 

Benzyne precursors 1-Aminobenzotriazole. Benzenediazonium-2-carboxylate. Benzo-l,2,3-thiadiazole-l,l-dioxide. o-Bromofluorobenzene. o-Bromoiodobenzene. Diphenylio-donium-2-carboxylate monohydrate. 

With benzyne, formed msitufrom 1-aminobenzotriazole, the2,5-diphenyl-... 

In the first reported reaction of benzyne with oxazoles, the isolated products were 2 1 benzyne oxazole adducts. In that reaction, the benzyne was generated in situ in a thermal process carried out at 101 °C. The initially formed adduct loses a nitrile to give an isobenzofuran, which adds a second molecule of benzyne. When benzyne is generated at 0°C from 1-aminobenzotriazole and lead tetraacetate under dilute conditions, the initial cycloadducts (59) are formed in essentially quantitative yield <90JOC929>. They can be handled at room temperature and can be decompose at elevated temperatures to isobenzofuran (60), which in the presence of other dienophiles leads to a variety of useful products (Scheme 16). 

The analog of 4 with a sulfinate group replacing the carboxylate exists in the ring-closed form 8 it decomposes in solution at 10°C to give benzyne, nitrogen, and sulfur dioxide.15 Oxidation of 1-aminobenzotriazole (9) with lead tetraacetate or other oxidants is another efficient source of benzyne via fragmentation of the intermediate nitrene 10.16... 

The lead tetraacetate oxidation of 1-aminobenzotriazole leads to benzyne (Eq. 107), whereas 2-aminobenzotriazole ring opens to Z,Z-mucononitrile (Eq. 108).398... 

Benzyne precursors 1-Aminobenzotriazole (see 1-Chlorobcnzotriazole). Benzenediazonium-2-carboxylate. 

Benzyne is also formed almost quantitatively on oxidation of l-aminobenzotriazole with NBS (2 equivalents) in the presence of tetracyclone, 1,2,3,4-tetraphenylnaphthalene is obtained in 88% yield. In the absence of a trap, o-dibromobenzene is obtained in 52% yield. No dimer is formed. Bromine is known to be an efficient scavenger of benzyne generated from this precursor.3... 

EHphenyl ether is often used as a high-boiling solvent but it can take part in an intramolecular cyclization under some conditions. The reaction is rapid in the presence of a palladium salt (review [B-41]) and an acid such as methanesul-phonic or trifluoroacetic add or of boron trifluoride. Addition of 4-phenyl-oxazole to benzyne (generated from 1-aminobenzotriazole and LTA) is more eflSdent when both reagents are simultaneously introduced through two syringes on opposite sides of the reaction vessel. 

Oxidation of heterocyclic amino derivatives yields various reaction products depending on the structure of the amine. 4-Benzylamino-3-methyl-4//-1,2,4-triazole is oxidized with DCT in chloroform to give the azomethine derivative 110 (69ZC325). l-Amino-4,5-diphenyl-l,2,3-triazole under the action of CBT forms diphenylacetylene 2-aminobenzotriazole yields cis, cw-l,4-dicyanobuta-l,3-diene and 1-aminobenzotriazole yields a mixture of chlorobenzene and o-dichlorobenzene. Oxidation of 1-aminobenzotriazole in the presence of tetraphenylcyclopentadienone leads to 1,2,3,4-tetraphenylnaphthalene via benzyne intermediate [68JCS(CC)1305 69JCS(C)1474] (Scheme 101). 

Benzyne generation. Several reagents [e.g., lead(IV) acetate, etc.] have been used to generate benzyne from 1-aminobenzotriazole. (V-Iodosuccinimide is now recognized as a superior reagent for this purpose. 

The oxidation of 1-aminobenzotriazole (ABT) by chemical reagents yields benzyne, an exceedingly reactive species, and two molecules of nitro-gen . The finding that benzyne, or its equivalent, is bound across two of the nitrogens of the prosthetic heme isolated from inactivated P450 enzymes suggests that the enzyme-catalyzed oxidation of ABT follows the same reaction trajec-tory 3 > The benzyne may add directly to the... 

Figure 7.19. Two alternative mechanisms for addition of the benzyne released from l-aminobenzotriazole (ABT) to the heme. The heme porphyrin framework is represented by a square of nitrogens, each of which represents one of the four nitrogens of the porphyrin.

Figure 7.20. Mechanistic alternatives for the P450-catalyzed generation of benzyne from l-aminobenzotriazole.

The reactive intermediate 1,2-dehydrobenzene (benzyne) is generated by oxidation of 1-aminobenzotriazole with lead(IV) acetate. It can be trapped with anthracene to form triptycene ... 

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