Arynes 1-aminobenzotriazole, oxidation

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

Aminobenzotriazole and related triazoles, all of which are aryne precursors, are autocatalytic inactivators of cytochrome P-450 and related oxidases. Evidence has been presented that the enzyme oxidizes these substrates to benzyne which then binds covalently to the heme prosthetic group of the enzyme, possibly as in 120, thus deactivating it. 

The third approach, like the first, constructs the B-ring. The key step, applied to the synthesis of A -nornitidine 710, involved aryne cycloaddition to a vinyl isocyanate. 4,5-Dimethoxybenzyne, generated from aminobenzotriazole 707 by Pb(OAc)4 oxidation, added to vinyl isocyanate 708 to give 709, which was not purified but converted directly to 710 (overall yield in the 30-35% range). 

The practice of using an insoluble polymer to isolate and kinetic-ally stabilize a reactive intermediate has been addressed in several reports, most commonly using DVB cross-linked polystyrene as a support. In these cases, the three dimensional structure of the polymer and rigidity of the polymer backbone diminish intramolecular reactivity between two sites on the same polymer bead. Physical constraints preclude any significant reaction between two different polymer beads. Similar, less dramatic reduced intramolecular reactivity has also been noted for reactive intermediates bound to linear polystyrene. For example, o-benzyne bound to linear polystyrene has been shown by Mazur to have enhanced stability relative to non-polymer-bound -benzyne (35). In this case, o-benzyne was generated by lead tetraacetate oxidation of a 2-aminobenzotriazole precursor, 1. Analysis of the reaction products after cleaving the benzyne derived products from the polymer by hydrolysis showed a 60% yield of aryl acetates was obtained (Equation 11). In contrast, the monomeric aryne forms only coupled products under similar conditions. Further comparisons of the reactivity of -benzyne bound to insoluble 2% or 20%... 

Similarly, upon treatment with the oxidant NIS, the aryne intermediates generated from 1-aminobenzotriazoles 16 undergo efficient intramolecular trapping by the pendant hydroxyl groups, leading to the fused iodinated oxygen heterocycles 17 (Scheme 12.6) [17]. 

Fragmentation Reactions. Oxidation of 1-aminobenzotriazoles with Pb(OAc) or MIS is used to generate arynes through the intermediacy of an aminonitrene 8. The subsequent fragmentation with loss of two molecules of leads to the corresponding aryne derivative (Scheme 12.8) [15]. 

Accordingly, arynes like benzyne (17), generated by Pb(OAc)4-oxidation of 3-aminobenzotriazole (16), undergo cycloaddition to oxazoles very readily [260] ... 

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