Benzyne generation, oxidative

In a sequence of cycloaddition and cycloreversion, 3-phenyl-l, 2,4-triazine 1-oxides react with benzyne, generated from 2-aminobenzoic acid (see Houben-Weyl, Vol. 5/2 b, p 622 ff), to give 2-phenyl-l, 3-benzoxazepines in moderate yield.419... 

Benzocyclobutenone was first prepared from 1 -bromobenzocyclobutene by hydrolysis followed by chromium trioxide oxidation.3 More recent procedures involve hydrolysis of 1,1-dichloro- or 1,1-dimethoxybenzocyclobutene which in turn have been obtained through cycloaddition of the appropriate 1,1-disubstituted ethylenes to benzyne generated either from anthranilic acid through diazotization5 6 or from bromobenzene through sodium amide treatment.7.3 Benzocyclobutenone has... 

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). 

Naphthalene oxides. The Diels-Alder reaction of 1,4-diacetoxybutadiene (1) with benzyne (generated from o-benzenediazonium carboxylate, 1, 46) gives the diacetate of l,4-dihydronaphthalene-cis-l,4-diol (2) in 53% yield. The product is converted into 3 by reaction with hydrogen peroxide and catalytic amounts of osmium tetroxide. The monotosylate of 3 is converted into 4 by treatment with base. This epoxy diol has the stereochemistry found in the carcinogenic epoxy diols formed as metabolites of aromatic hydrocarbons. The dimesylate of 3 is converted into the syft-diepoxide 5. 

Benzyne can be trapped in 1,3-dipolar cycloaddition reactions provided that the 1,3-dipolar species is sufficiently stable under the conditions necessary for benzyne generation. As an illustration of this, benzyne reacts with the nitrile oxide group in preference to the furan ring of compound 19, whereby adduct 20 is obtained.27 Benzyne and the nitrone 21 give adduct 22,28 and... 

Benzoselenadiazole (128) behaves as a heterodiene toward dimethyl acetylenedicarboxylate, with which it gives the quinoxaline 124 and selenium. But 128 reacts differently with benzyne (generated from 4 or from 9) to give the 1,2-benzisoselenazole derivative 132 (88%) and a small amount of a cis,trans stereoisomer of 132.82 The analogous adduct 131 is obtained in lower yield from benzyne and 2,1,3-benzothiadiazole (127). The structure of these benzyne adducts is strikingly reminiscent of 135, which is obtained from a photochemical addition of dimethyl acetylenedicarboxylate to 126 via a nitrile oxide intermediate.84 However, for reasons given elsewhere,82 a nitrile selenide is unlikely to be an intermediate in the formation of 132, which is better explained by the mechanism outlined in Scheme 16. As in the case of thiophen (Section V,B), this is a 1,3-cycloaddition (in one or two steps) of benzyne to the heterocycle, enabled by the use of d orbitals on the sulfur or selenium atom. 

The earliest example is the addition of benzyne (generated from 4 or by diazotization of anthranilic acid in situ) to N-phenyl sydnone (3-phenyl-l,2,3-oxadiazolium 5-oxide, 138)88 spontaneous loss of carbon dioxide from the intermediate adduct 139 gives 2-phenylindazole (140). Later workers have obtained 140 in higher yield (73%) and the corresponding 2,3-disubstituted indazoles from two other sydnones using benzyne generated by oxidation... 

Phenazine is similarly unreactive toward benzyne (by oxidation of 9), which gave only biphenylene and small amounts of unidentified highly colored products.81 On the other hand, the benzo[h]quinolizinium salt 175 reacts like anthracene with benzyne (generated by aprotic diazotization of anthranilic acid in refluxing acetonitrile) to give the Diels-Alder adduct 176 (78%).100 Aromatization of 176 to 9-(2-pyridyl)anthracene (177) is accomplished in refluxing acetic anhydride in the presence of sodium acetate. 

Generation of benzyne (see also 1, 560). Campbell and Rees1 point out that the generation of benzyne from this precursor by oxidation with lead tetraacetate differs from other methods in that, in the absence of a trapping agent, the dimer, diphenylene, is formed in yields as high as 83%. The trimer, triphenylene, is formed in less than 0.5% yield. Addition reactions of benzyne generated in this way with 1,3-dienes have been discussed.2... 

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... 

The reactivity of functionalised crosslinked polymers may significantly differ from that of analogous soluble reagents. Polymer-bound benzyne, generated by Pb(OAc)4-oxidation of resin-bound 1-aminobenzotriazole 3, for example was converted into aryl acetates 4. This reaction was not observed if an analogous 1-aminobenzotriazole derivative 6 was oxidised in solution, where the formation of dimers (7 and 8) was predominant (Scheme 1.6.3). 

Imidazole, benzimidazole, and benzotriazole give N-phenyl derivatives in low yield with benzyne ° l-methylbenzotriazole understandably fails to react. In contrast, 2-methylbenzotriazole reacts with benzyne (from oxidation of 9 with lead tetraacetate) to give 1-phenylbenzotriazole (112) (22%). The mechanism suggested to account for incorporation of benzyne and oxidative removal of the JV-methyl group is outlined in Scheme 13 formaldehyde may be further oxidized under these conditions. 2-Benzylbenzotriazole and benzyne under the same conditions afforded 112 and benzoic add. When benzyne was generated from 4 instead, it reacted with 2-methylbenzotriazole to give phenazine (2%) and no 112. ... 

Benzynes, generated from Kobayashi precursors (2-trimethylsilyl)-phenyl triflates), undergo 7i-insertion reactions into the P=N bond of N-aryl iminophosphoranes to afford, eventually, a-aminoaiyl-diphenyl-phosphine oxides (Scheme 3). ... 

Mono- or di-arylaied products may be formed by a-arylation of -dicarbonyl compounds, such as malonamide esters, with arynes generated by reaction of fluoride with ortho-silylaryltriflates. A similar method of benzyne generation has been used in the a-arylation of -ketoamides in a procedure which may be modified to yield asymmettic products. The reaction of 2-haloacetanilides with arynes in the presence of a palladium catalyst may produceiV-acylcarbazoles such as (26). Possible pathways are initial formation of a palladacycle with aryne followed by oxidative addition of the haloacetanilide, or direct insertion of the palladium into the carbon-halogen bond of the acetanilide followed by carbopalladation of the aryne. ... 

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. 

When benzyne is generated by aprotic diazotization of anthranilic acid in boiling 1,2-dimethoxyethane in the presence of substituted benzene-2-diazo 1-oxides (o-quinonediazides), dibenzofurans are obtained in moderate yields (Scheme 64). ... 

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