Benzyne, as intermediate

Also during the 1940s, the formation of biphenyl (24) from fluorobenzene (26) and phenyl hthium (25) in an uncatalyzed reaction (Scheme 1.9) led Wittig to propose a dehydrobenzene, specifically an ortho-benzyne, as intermediate [39, 40], the formation of which was confirmed by Roberts in 1953 [41]. Modem arylation methodologies based on arynes as key intermediates are reviewed by Yu Chen and Richard Larock in Chapter 12. 

Alternative methods for its generation have made it possible to use benzyne as an intermediate m a number of synthetic applications One such method involves treating o bromofluorobenzene with magnesium usually m tetrahydrofuran as the solvent... 

On the other hand labeling studies have shown that the base promoted hydro lysis of chlorobenzene (second entry m Table 24 3) proceeds by the elimination-addition mechanism and involves benzyne as an intermediate... 

An early ease in whieh the existenee of benzyne as a reaetion intermediate was established was in the reaction of chlorobenzene with potassium amide. Carbon-14 label in the starting material was found to be distributed in the aniline as expeeted for a benzyne intermediate. ... 

Ni- and Pt-Cycles as intermediates in reactions of Ni(0)- and Pt(0)-complexes with benzyne or related small-ring alkynes 97CB1029. 

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). 

There seem to have been only two investigations on dediazoniations in a protic solvent, where the observed products indicate that, in addition to DN + AN solvolysis, an aryne is likely to be present as a metastable intermediate. Broxton and Bunnett (1979) have found that 3-nitroanisole is formed in the dediazoniation of 2-nitroben-zenediazonium ions in methanol in the presence of methoxide ions. This has to be interpreted as a product arising from 3-nitro-l,2-benzyne as an intermediate. The occurrence of the aryne mechanism in poly (hydrogen fluoride)-pyridine mixtures, as discovered by Olah and Welch (1975), is mentioned in Section 8.2. 

The same 1 1 product ratio was found with iodobenzene-l-14C. This result clearly indicates that the same intermediate intervenes with both halides. The most likely candidate is benzyne, as shown, which would easily accommodate the distribution of the label. Also, the intermediate is not likely to contain Cl or I, because its selectivity ratio in the second step would then not be the same. 

Various organolithium intermediates may be posmlated for the synthesis of functionalized indoles and other heterocyclic compounds, from substituted Af-allylanilines (331a-c) or the cychc analog 332, on treatment with f-BuLi. For example, in equation 81 intermediate 333, derived from 331a, was quenched with deuterium oxide. Participation of benzyne metallated intermediates, such as 334, derived from 332, is surmised in equation 82 and other processes. The products of equations 81 and 82 can be characterized by H and NMR spectra . 

Another reaction which requires o-quinoneallides as intermediates is the synthesis of chromenes from benzyne and ,/3-unsaturated aldehydes (Scheme 5).189 The formation of the unstable benzoxete was confirmed by isotope labeling. Yields are in the range 4—40%. 

Special iodonium salts. A range of o-trimethylsilyl-phenyliodonioarenes [111] and heteroarenes [112] as well as some similar Wc-compounds coming from norbornadiene [113] and o-carborane [114] have been obtained from the corresponding bis trimethylsilyl precursors upon reaction with one equivalent of (diacetoxyiodo)benzene. These compounds are useful for their facile in situ conversion into benzyne-type intermediates for benzyne itself the whole procedure is available in Organic Syntheses [115]. A recent improvement involved the synthesis of a new benzyne precursor illustrated in Scheme 38 [116]. 

The intermediate is called benzyne as it is an alkyne with a triple bond in a benzene ring. But what does this triple bond mean It certainly isn t a normal alkyne as these are linear. In fact one tc bond is normal—it is just part of the aromatic system. One tc bond—the new one—is abnormal and is formed by overlap of two sp2 orbitals outside the ring. This external tc bond is very weak and benzyne is a very unstable intermediate. Indeed, when the structure was proposed few chemists believed it and some pretty solid evidence was needed before they did. We shall come to that shortly, but let us first finish the mechanism. Unlike normal alkynes, benzyne is electrophilic as the weak third bond can be attacked by nucleophiles. 

Carbenes have also been considered as intermediates in the thermal dissociation of 2-alkoxy-l,3-dithioles (Section III,B,4) and in the reactions of carbon disulfide with activated alkynes and with benzyne. Another type of deprotonation may occur with 1,3-dithiolium cations containing phenolic hydroxyls. Thus, treatment of 4-aryl-2-(4-hydroxy-phenyl)-1,3-dithiolium perchlorate with triethylamine gives 135, stabilized by its zwitterionic structure 136. ... 

After extensive works by Wittig, Roberts and colleagues, and Huisgen and colleagues unveiled the features of this interesting intermediate having a carbon-carbon triple bond, Wittig then accepted dehydrobenzene (which he called benzyne) as a reality. 

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... 

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