Benzyne formation from

Other examples of the ElcB pathway are benzyne formation from C6HsF (cf. p. 174), reversal of simple nucleophilic addition to 0=0, e.g. base-induced elimination of HCN from cyanohydrins (20 cf. p. 212),... 

Successful lithiation of aryl halides—carbocyclic or heterocyclic—with alkyUithiums is, however, the exception rather than the rule. The instability of ortholithiated carbocyclic aryl halides towards benzyne formation is always a limiting feature of their use, and aryl bromides and iodides undergo halogen-metal exchange in preference to deprotonation. Lithium amide bases avoid the second of these problems, but work well only with aryl halides benefitting from some additional acidifying feature. Chlorobenzene and bromobenzene can be lithiated with moderate yield and selectivity by LDA or LiTMP at -75 or -100 °C . 

Benzyne generated from 2-carboxybenzenediazonium chloride reacted with sulfur monochloiide to give dibenzothiophene 13 (8-10%) and thiantherene 14 (26-35%) (1989SUL83). A mechanism involving the addition of sulfur mono-chloride to benzyne with the formation of betaine 15 followed by the elimination of SCI2 to afford benzothiirene 16 and a further reaction with another benzyne molecule or dimerization to thianthrene 14 is given in Scheme 8. 

There has been a review of didehydropyridines, focusing on then formation from halopyridines and base.123 The reactions of tri-p-tolyloxonium salts with hydroxide in water yield a mixture of p- and m-cresols via a benzyne intermediate,124 as shown in Scheme 7. A benzyne intermediate, generated by loss of lithium fluoride, is also implicated in the reaction of organolithium reagents with fluoro-AyV-diallylanilincs leading to 3,4-disubstituted indolines.125 The reaction of benzyne with 1,8-diethynylnaphthalene has been shown to yield benzo [a]pyrene.126... 

Okuma et al. <1998CL79, 2000BCJ155, 1999J(P 1)2997, 2005H(65)1553> published a series of papers describing reactions of various thioketones with benzyne generated from 2-trimethylsilylphenyl trifluoromethanesulfonate 96, phenyl[2-(trimethylsilyl)-phenyl]iodonium trifluoromethanesulfonate 97, or benzenediazonium-2-carboxylate 98, which led to the formation of benzothietes. Compounds 96-98 are good precursors of benzyne, but not in the... 

With the discovery of benzyne formation by pyrolysis of phthalic anhydride, a new field was opened for the investigation of aryne reactions at high temperatures. A first concern was to determine the generality of aryne formation from aromatic acid anhydrides. Such syntheses could be of considerable significance because of the enormous quantities of aromatic mono- and polyanhydrides available from petroleum aromatics by oxidation. 

Thermolysis of 6 at 60°C gives the benzyne complex 7. This reaction is significantly retarded by excess trimethylphosphine, which indicates that benzyne formation occurs from a 16-e intermediate. An X-ray crystal structure of 7 was reported. Bond lengths for the benzyne unit are given in Table III. No reactions of 7 have been reported. 

An unusual 1,3-cycloaddition of benzyne across a C=N-Se grouping in a 1,2,5-selenadiazole leads to the formation of the isoselenazole ring. The benzyne, generated from anthranilic acid, reacts with 3,4-diphenylselenadiazole 81 to afford 3-phenylbenzisoselenazole 82 as confirmed by mass spectrometry and the detection of benzonitrile, but the reaction has no practical synthetic value (Scheme 28) <1988J(P1)2141>. 

One of the simplest routes to benzyne starts with aniline which is converted to benzenediazonium ion. Benzyne is liberated when this ion is deprotonated by acetate base in solvents such as benzene, Eq. (20). Detracting from this approach, however, are competing reactions in which phenyl radicals and phenyl cations are formed. Presently it is possible to minimize the importance of radical chain side reactions and thereby to favor benzyne formation by adding a radical trapping agent such as 1,1-diphenylethylene. 8S ... 

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 reaction of benzyne with pyridine has been studied only at 690°C (benzyne generated from phthalic anhydride).96 The main condensable products in order of decreasing abundance were naphthalene, phenyl-pyridines (three isomers), bipyridyls, and quinoline. It is necessary to consider two modes of 1,4-cycloaddition, followed by rearomatization, to account for the formation of naphthalene (Eq. 4) and quinoline (Eq. 5), respectively. 

Immobilisation prevents the benzyne intermediates from dimerisation and allows the alternative transformation which in solution is too slow to compete with dimerisation. Applications of functionalised polymers for monoprotection (many examples were contributed by Lezno, A"6.146-150 further examples see Refs. - SZ) or monoactivation of symmetrically difunctionalised molecules as well as their use to promote the formation of large rings are based on this site isolation or pseudodilution effect . ... 

Vinylbenzo[fc]thiophen and benzyne (from o-bromofluorobenzene) afford 62 (13%) dehydrogenation of the 1 1 adduct 61 is possibly induced by attack of benzyne. Formation of the 1 1 adduct 45 (14%), from benzyne and l,3-diphenylbenzo[c]thiophen (143) is accompanied by some desulfurization to give 9,10-diphenylanthracene (9%) 45 also loses sulfur at 250°C. 

In spite of the ready formation of triptycene from anthracene and benzyne, the azatriptycene 167 cannot be obtained directly from acridine and benzyne. Instead, only biphenylene (17) was obtained (benzyne generated from 9), or 2-fluorobiphenyl (using o-fluorophenyllithium), or the products were... 

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