Reactions of benzynes

Benzyne is an extremely reactive species and is generated in situ for obtaining various products. 

As already stated, aryl halides on treatment with a strong base such as KNH2 generates benzyne. The benzyne further reacts with nucleophile (NHJ) to give aniline. 

Various products can be synthesized by the reaction of a benzyne with different compounds. 

Benzyne undergoes [4+2]-cycloaddition reactions in which it acts as a dienophile. The Diels-Alder reaction of benzynes give fused- or bridged-ring systems. 

Benzyne undergoes [2+2] -cycloaddition reaction with alkenes to give four-membered rings. 

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In the reactions of benzyne with enamines, arylated enamines or amino-benzocyclobutenes can be obtained, depending on reaction conditions and the structure of the enamine. Thus the presence of a proton source such as a secondary amine will favor the enamine product through capture of the zwitterionic intermediate, whereas in the absence of protons one sees... 

Elegant methods for determining the relative reactivity of transient intermediates have been developed.6 Consider the reactions of benzyne with water and hydroxide ions ... 

Although benzobarrelene has been used in a number of recent studies, the best available published synthesis" starts with the Diels-Alder reaction of j8-naphthol and maleic anhydride, affording benzobarrelene in ca. 1% yield after five further steps. Minor improvements allow small quantities of benzobarrelene to be prepared in an overall yield of ca. 10%. The reaction of benzyne with benzene is relatively inefficient, giving benzobarrelene in ca. 2% yield. When benzyne is generated by decomposition of benzenediazonium-2-carboxylate at high dilution in benzene, the yield of benzobarrelene is raised to 14%. The reactions of benzyne with other aromatic substrates are equally inefficient. 

The reactions of benzyne and carbenes with phosphabenzenes and of carbenes with phospholes have been investigated. Whereas benzyne reacted in the anticipated manner with (27) to give (28), carbenes, or their precursors, reacted in a curious manner to give substituted benzenes (30). Good evidence for the intermediacy of the phosphepin (29) came from the finding that closely related compounds, such as (31), also decomposed to give substituted benzenes. The nature of the eliminated phosphorus entity has still to be determined. 

However, in a re-investigation of the reaction of benzyne with benzene 39>, it was shown that the original method of isolating benzene-diazonium-2-carboxylate resulted in the contamination of the zwitter-ion with silver salts 40>41). In the absence of silver ions biphenylene, and... 

The analogues of the other products formed in the reaction of benzyne with benzene, 2,3,4,5-tetrafhiorobiphenyl (23), octafluorobiphenylene, and tetrafluorobenzocydo-octatetraene (26), have not been detected in the reactions of tetrafluorobenzyne with benzene. 

Several papers describing reactions of benzyne with substituted styrenes 98-100) appeared before we 101> and a number of other groups 102> 103,56) began investigating the reactions of the tetrahalogenobenzynes with styrene and substituted styrenes. No well defined product had been obtained in the reaction of benzyne with styrene itself 104> although this reaction has now been investigated in some detail los.ioe.ioi). The reaction of benzyne with 2,4,6[2H3]styrene leads either to 9-phenyl-... 

The reactions of benzyne with enol-ethers and enol-acetates have been much studied very recently 115-118). We were not surprised therefore to isolate a product derived from the attack of tetrafluorobenzyne on the bis-enol-ether (75). This product is derived from a (2 + 2) n cycloaddition and the available evidence suggests that this product has the structure (78). 

Little evidence for the production of simple products was obtained using tetrahydrofuran, but more complex products, for example the compound (91), have been reported very recently from the reaction of benzyne with tetrahydrofuran 131>. 

Products derived from intermediate zwitter-ions have been obtained in the reactions of benzynes with tertiary amines 1>. Benzyne generated by the reaction of -butyl-lithium with fluorobenzene interacts with AT.Af-dimethylaniline to yield iV-methyl diphenylamine and AT-ethyl diphenylamine 132,133). Using the reaction of chlorobenzene with n-butyl-lithium to generate benzyne resulted in the formation of increased amounts of 2-A7,AT-dimethylaminobiphenyl 132,133)... 

The reaction of benzyne with furan was the first example of a Diels-Alder reaction of benzyne to be studied b. No authenticated examples of arynes are known which fail to give cyclo-adducts with furan i38>. The tetrahalogenobenzynes all form the expected adducts 103, X = F 6), Cl 57>i39)j gr 59) or i 59)). d0 other highly fluorinated arynes i40,i4i>. The isomeric adducts (104) and (105) have been detected by 19F n.m.r. spectroscopy when the dilithio-compound (12) was allowed to decompose in the presence of furan 28 103). 

The reaction of benzyne with cyclohexadiene has been known for some time 4>, but although a number of steroidal cis-dienes are readily available no reactions with arynes had been reported prior to our beginning such investigations 145>. This was somewhat surprising in view of the number of reports concerning the modification of steroids by means of reactions with carbenes 146 i49) and the known Diels-Alder reactions of steroidal dienes and trienes iso.isi). 

We have also investigated the reactions of benzyne and tetrachlorobenzyne with the rings A/C cis-diene (117), both of which gave the a-adducts (118, X = H or Cl)... 

Derivatives of the naphthalen-l,4 -imine ring system (2) have become available only since the discovery of cycloaddition reactions of benzyne, on the one hand, and the recent rapid development of isoindole chemistry on the other. 

The major product (21-37%) from the reaction of benzyne with N-phenylpyrrole is the 2 1 adduct (167), the formation of which is explicable in terms of the cyclization of either one of two intermediate zwitterions, 165 or 166. Alternatively, prototropic shift within the intermediate (166) accounts for the formation of the a-naphthylamine (147) (4-6% yield). Other benz[o]carbazole derivatives (168 and 169)... 

The formation of a small amount of naphthalene as a by-product of the reaction of benzyne with iV -methylpyrrole was noted by Wittig and Behnisch. Some related examples have recently been described. The tetrachloronaphthalen-l,4-imine (108) with benz5me gave N-methylcarbazole, which it is tempting to see as arising from the reaction of an intermediate zwitterion (compare 166) with another molecule of benzyne or, more likely, a benzyne precursor. The complementary product, 1,2,3,4-tetrachloronaphthalene, was not identified in this case. 

For a review of benzynes as dienophiles, see Hoffmann Dehydrobenzene and Cycloalkynes, Academic Press New York, 1967, pp. 200-239. For a review of the reactions of benzynes with heterocyclic compounds see Bryce Vernon Adv. Helerocycl. Chem. 1981,2, 183-229. 

Reactions of Benzyne with Heterocyclic Compounds M. R. Bryce and J. M. Vernon, Adv. Heterocycl. Chem., 1981, 28, 183-229. 

There is some evidence that the cycloaddition reaction of benzynes with 1-substituted pyrroles may proceed in two steps via a zwitterionic intermediate and that the reaction is thermally reversible, for although 1-methylpyrrole yields the [w4 + w2] adduct (258) with... 

Reaction of benzyne with arsabenzene affords l,4-etheno-l,4-dihydro-l-arsanaphthalene (192) from which an etheno bridge can be removed with 3,6-di(2-pyridyl)-l,2,4,5-tetrazine (184) to afford, via the polycyclic intermediate (193), the arsanaphthalene (194) (79CC880). 

V-Hydroxycarbazole (326) was first postulated (64JOC2808) as an intermediate in the reaction of benzyne with nitrosobenzene, which gave N-phenylcarbazole. Later it was obtained in 1% yield from diazotized anthranilic acid and nitrosobenzene, while tetrahalogenated benzynes,... 

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... 

A reaction of benzyne with the 6-unsubstituted 1,2,4-triazine-l-oxides 58 (R1 =Ph, R2 = H, Me) gave the 1,3-benzoxazepines 59 (R1 Ph, R2 = H, Me) (15-20% yield) and the 6-(t>-hydroxyphenyl)-l,2,4-triazines 60 (30-40% yield) via the (C6NO)-l,3-dipolar cycloadducts (Equation 14) <1996H(43)2091>. From the cycloadduct, sequential N-O bond cleavage, a 1,3-shift, and nitrogen loss provided access to 59 a competing 1,5-shift, followed by aromatization, led to the alternative products 60. 

Triptycene is the Diels-Alder cycloaddition product from the reaction of benzyne with anthracene (compound A). Although anthracene is aromatic, it is able to undergo cycloaddition at the center ring with a dienophile because the adduct retains the stabilization energy of two benzene rings. 

Reaction of benzyne with tertiary aliphatic amines to give anilines via Sommelet-Hauser and/or Stevens-type rearrangements of the intermediate ylid has been documented.362 363... 

Another example is the reaction of benzyne with 1-methyl- (and benzyl)-3, 3-dimethylbenzo[d]-l,3-azasiloline (see their preparation in Section IV.A.2.p). Stevens rearrangement product is obtained (48%) as a single compound. If a Me on nitrogen is replaced by an Et, then Hoffmann elimination occurs.251 It should be noted that an Y-alkyl MSMA is converted into an Y-aryl RSMA in the former case and into a Y-aryl MSMA in the latter case. 

The initial formation of the benzodithiete 19e, as an intermediate in the reaction of benzyne with elemental sulfur, was suggested on the basis of its secondary reaction that traps another benzyne molecule to give thianthrene 139, or o-C6U4S2 19e to give tetrathiocin 140 (Scheme 17) <2004JOC5483>. 

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