The formation of benzyne

In a synperiplanar elimination the leaving groups lie in the same plane on the same side of the molecule (Section 6.2. Ij. 

Reaction of halobenzenes (CeHsX) with a strong base (e.g. NaNH2 in NH3) leads to the elimination of HX and the formation of benzyne (in a synperiplanar elimination reaction). The new Jt-bond that is formed (by overlap of two sp  

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The formation of benzyne as an intermediate was first postulated by Roberts et al. (1953) for the amino-de-chlorination of chlorobenzene (see Roberts, 1990, p. 110). 

Figure 8-5. Reactions of halobenzene derivatives with nucleophiles, a) Unactivated compounds are extremely inert and only react by mechanisms that involve the formation of benzynes. b) The presence of the electron-withdrawing nitro group, which can stabilise an anionic intermediate by the delocalisation of the charge onto the electronegative oxygen atoms, allows facile nucleophilic substitutions.

Some evidence for the formation of benzyne in the cathodic reduction of o-dibromobenzene 173 has been obtained ... 

The formation of benzyne from chlorobenzene at 690° is further substantiated by the presence of a small amount, 0 5 on the same scale, of biphenylene among the products. The high-temperature behavior of chlorobenzene thus parallels somewhat its behavior at ordinary tempera-... 

The data strongly suggest the formation of benzyne from o-sulphobenzoic anhydride—from the products of its reaction with benzene by 1,2- and 1,4-addition (naphthalene, phenylnaphthalene) and insertion (biphenyl, about four times as much by weight as from benzene alone). The uncondensed gases from the reaction were a 1 1 mixture of sulphur dioxide and carbon dioxide. This, in addition to the other products, indicates that the first step of Path 2, loss of sulphur dioxide, is the dominant primary process. However, the resulting zwitterion, unlike its cationic counterpart in the mass spectrometer, does not go on to lose carbon monoxide it stabilizes itself more easily by losing carbon dioxide... 

As you would expect, the formation of benzyne is the slow step in the reaction so there is no hope of isolating benzyne from the reaction mixture or even of detecting it spectroscopically. However, it can be made by other reactions where there are no nucleophiles to capture it. The most important is a diazotization reaction. 

To mitigate the formation of benzyne intermediates that occur with o-halophenyl intermediates, m-fluoroaniline was used (1). 

Fields and Meyerson were the first to show the utility of phthalic anhydride as a source of benzyne in the gas phase.s ) The formation of benzyne from phthalic anhydride, Eq. (31) is directly analogous to the formation of mfe 76 in the mass spectrum of phthalic anhydride, Eq. (32). The benzynes... 

A special reaction of this type is the formation of benzyne. o-Fluorobromobenzene reacts with lithium amalgam in ether or furan with an intermediate formation of benzyne. In the former medium, diphenylene and small amounts of triphenylene and 9,10-dimer-cura-9,10-dihydroanthracene were formed, whereas the major product (76%) in furan was 1,4-dihydronaphthalene-1,4-endoxide [64]. 

Benzynes. Review of the formation of benzynes, for example by the reaction of phenyllithium on fluorobenzene, 1-fiuoro- and 2-fluoronaphthalene. For related observations, see Phenylsodium. 

Cyclic 1,3-dienes (with an inherent s-cis conformation) can react with benzyne to afford Diels-Alder adducts in high yiel (Scheme 114). The addition to furan (228), reported by Wittig and Pohmer in 1955," is so efficient that it has become a diagnostic test for the formation of benzyne. Cyclopenta-diene"3 > and tetracyclone (492) also serve as standard assay reagents. 

Observations of the UV absorption4 attributable to benzyne in the vapor phase, evidence from time-resolved mass spectrometry,5 and more recently of the IR spectrum6 of benzyne in a matrix at very low temperature leave no doubt as to the existence of such a transient intermediate. Its lifetime in solution is extended when benzyne is supported on a polymer phase.7 Results of competitive trapping experiments, when benzyne is generated from different precursors, and the classical experiments of Roberts et al. on cine-substitution in the amination of chlorobenzene confirm the formation of benzyne as an intermediate.8,9... 

The formation of benzyne via o-FC6H4MgBr from o-bromofluorobenzene and magnesium is closely related in mechanism to the base-induced eliminations, but the reaction conditions for the Grignard method (in refluxing tetrahydrofuran) are often more convenient. Benzyne is also produced from o-bromofluorobenzene and butyllithium, and hexachlorobenzene is the usual precursor for generation of tetrachlorobenzyne (Eq. 1). 

Benzyne is reactive as a dienophile and provides many examples of Diels-Alder addition. It is efficiently trapped by anthracene to give triptycene and by tetracyclone to give 1,2,3,4-tetraphenylnaphthalene via decarbonylation of adduct 23, reactions which are commonly used to quantify the formation of benzyne under given conditions. 

Piperidine or lithium piperidide and benzyne form N-phenylpiperidine, as expected,39,106,107 but the same product (40-50%) was also obtained unexpectedly from N-methyl piperidine, fluorobenzene, and phenyllithium before the formation of benzyne under these conditions was properly recognized.21... 

Previously, Andersen et al. had attempted to prepare sulfuranes from the reactions of diaryl sulfoxides with aryl Grignard reagents and aryl lithium agents. They reported that the reactions give initially the corresponding triaryl sulfoni-um salts, from which two pathways, namely the formation of tetraaryl sulfuranes and the formation of benzyne, take place simultaneously, on the basis that they obtained diaryl sulfides and biaryls derived from benzyne, as shown in Scheme 7 [37]. 

Treated with NaNH2, aromatic halides lead to the elimination of a hydrogen halide and the formation of benzyne (refs. 74-77). This reaction can be followed by the addition of the amide ion, resulting in the obtention of anilines. The reaction occurs on the two reactional centres of the benzyne. Using 14C labelled chlorobenzene leads almost to a 1 1 ratio of aniline 1-I4C and 2-14C (Fig. 13). Fluorides are less reactive than chlorides which are less reactive than bromides. When the halobenzene bears a substituent there are several possibilities (Fig. 13). With a halogen in the meta position, two benzynes are possible, the direction of the elimination is predictable on the basis of which hydrogen is more acidic. With an ortho or a para substituent only one benzyne is produced but the amination takes place according to the nature of the substituent (refs. 74-79). 

Benzyne (1) and cyclopentylidenecarbene (121) are isoelectronic. The formation of benzyne from 121 in the gas phase was first proposed in 1979, and the ensuing studies have recently been reviewed. The rearrangement of 121 -> 1 was suggested from pyrolysis results with the alkylidene Meldrum s acid 122. Besides high yields of the expected carbon dioxide, acetone and cyclopentadiene, substantial amounts of aromatic products such as biphenylene (27%) and triphenylene (12%) were obtained that were most easily accounted for as a consequence of rearrangement of carbene 121 to benzyne and subsequent di- or trimerization. 

Piperidine or lithium piperidide and benzyne form N-phenylpiperidine, as expected, but the same product (40-50%) was also obtained unexpectedly from V-methylpiperidine, fluorobenzene, and phenyllithium before the formation of benzyne under these conditions was properly recognized. A series of N-alkylmorpholines gives secondary and tertiary aniline derivatives 213 and 214 when treated with bromobenzene and sodium amide. A route for formation of these products via the ylid 211 is outlined in Scheme 19, in which the formation of 211 is similar to that of 16 in Scheme 2 and the step 212 -+ 213 is similar to the decomposition of 33 in Scheme 5. The final... 

The formation of benzyne from 6>-fluorobenzene proceeds by initial formation of a Grignard reagent, followed by loss of BrMgF. 

Hydrolysis of Chlorobenzene (Dow Process). In this process chlorobenzene is heated at 350 °C (under high pressure) with aqueous sodium hydroxide. The reaction produces sodium phenoxide, which, on addification, yields phenol. The mechanism for the reaction probably involves the formation of benzyne (Section 21.1 IB). 

It may be remembered (Chapter 7, Scheme 7.13) that treatment of aryl halides, such as bromobenzene (CeHsBr), with liquid ammonia (NH3(i)) (Equation 10.22) results in the formation of benzyne (C6H4), and the capture of the latter by ammonia (NH3) produces aminobenzene (aniline). 

Greaney et al. introduced the Heck reaction to the benzyne three-component coupling to prepare 1,2-functional-ized arenes 28 and 29. Alternatives to allyl chlorides as the initial carbopalladation electrophile were presented, that is, methyl bromoacetate and benzyl bromides, thus avoiding the formation of benzyne/benzyne/allyl by-products and therefore improving the efficiency of the reaction [39], When using aryl iodides as the electrophilic partners, highly functionalized biaryl compounds 30 are obtained (Scheme 3.20) [40]. 

Kitamura and coworkers reported that treatment of (phenyl)[2-(trimethylsilyl) phenyl]iodonium triflate with TBAF results in the formation of benzyne, which can be trapped with furan and other dienes in cycloaddition reactimis [35, 267, 268]. This feature was recently utilized with an iodonium salt containing an ort/io-(pyridyldiisopropyl)silyl group [269]. Diaryliodonium salts are also useful in covalent grafting of carbon surfaces useful in materials chemistry [270-273]. 

Their formation has been explained (Buser, 1979) in a laboratory study by invoking the formation of benzyne intermediates or the re-arrangement of. intermediates formed between an ortho-chloro phenyl radical with a chlorobenzene. 

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