Benzynes addition reactions

The chemistry of dehydrobenzene, the parent aryne, has become well established during the past almost twenty years 4>. It is essentially the chemistry of a short lived (half-life ca. 10-4 sec.), and highly electrophilic intermediate. It reacts with a large number of nucleophiles, and undergoes cyclo-addition reactions with a wide variety of compounds. A number of observations have led us, and others, to concentrate our efforts on the tetrahalogenobenzynes. It seemed reasonable to predict that the presence of four electron withdrawing substituents on the aryne (1) would result in a significant increase in the electrophilicity compared with that of benzyne. 

An elimination/addition reaction is another distinct type of reaction mechanism that occurs in aromatic systems. In these mechanisms, the elimination involves the loss of an HX molecule. While this may seem like a dehydrohalo-genation as seen in Organic Chemistry 1, it really is a different reaction. The HX loss leads to the formation of a benzyne intermediate (see Figure 8-2). The mechanism ends with addition to the bond formed by the loss of HX. 

The Dow Process utilizes an elimination/addition reaction to convert chlorobenzene to phenol. The proposed mechanism for this reaction is shown in Figure 8-3. The high-temperature reaction begins with chlorobenzene and aqueous sodium hydroxide. Note that this mechanism starts with the hydroxide attacking as a base, beginning dehydrohalogenation to form benzyne. The second hydroxide ion attacks as a nucleophile to form a carbanion intermediate, which behaves as a base in the last step to yield the final product. 

Quinoxaline 1-oxide (209) reacts with phenyl isocyanate to give 2-anilinoquinoxaline (210) together with 1,3-diphenyl-l-(2-quinoxalinyl)-urea (211) and cyclized oxidation product of the urea 212.215 2-Quinoxalinone 4-oxide (205) and its 1-methyl derivative undergo addition reactions, e.g., with phenyl isocyanate and benzyne to give compounds 214 and 216, respectively.216 These reactions are formulated as proceeding via the intermediate cycloadducts 213 and 215. Compound 216 has also been obtained by photolysis of 3-(o-hydroxy-phenyl)quinoxaline 1-oxide.51 1,3-Dipolar cycloaddition of quinoxaline... 

Bromobenzyl 2-fluorophenyl thioether, derived from 2-fluorothiophenol and 2-bromobenzyl bromide, is a source of a benzyne through reaction with /-butyllithium. Simultaneously, the bromobenzyl moiety generates the tethered aryllithium 405 and an intramolecular anionic cyclisation is promoted. The sequence is completed by the addition of an electrophilic species leading to 1-substituted b/Z-dibenzol //]thiopyrans (Scheme 121) <2002CEJ2034>. 

From the addition reactions of phthalic anhydride with pyridine, naphthalene was formed in much greater quantity than quinoline isoquinoline was either totally absent or present in only minute amounts. These facts indicated (a) if there were much 1,2-addition of benzyne, it occurred predominantly at the 1,2 and 3,4 atoms in pyridine (b) 1,4-addition took place at carbon atoms in preference to a nitrogen and a carbon atom. Studies with other systems indicate that arynes have a decided preference for 1,4- over 1,2-addition. 

New nickel-benzyne complexes (143-147) have been prepared by reaction of o-dihaloarenes with Ni(COD)2 in the presence of a trialkylphosphine followed by reduction of the oxidative addition product with either Li or 1% Na/Hg in ether [e.g., Eq. (23)]. The oxidative addition reaction depends on the nature of substituents on the arene and fails to occur when strong electron-donating groups are present. Based on NMR and mass spectrometry (MS) data, the new complexes were formulated as monomeric. It had been... 

Although there is ample evidence for nucleophilic additions to benzyne la> and some other unstable angle strained cycloalkyne intermediates 15,27,31,205 207), only a few addition reactions to isolable angle strained cycloalkynes are known which can be classified as nucleophilic. Hydroxylamine and hydrazine add to (31) to yield the corresponding oxime and hydrazone, resp. 208). 

Manganese(m) acetate oxidation (cf. Vol. 3, p. 34) of camphene gives (186) as a 95 5 mixture by carboxymethyl radical insertion no rearranged products were obtained, in contrast to /3-pinene which gave Wagner-Meerwein products only, and no free-radical insertion.279 The E- and Z-isomers of (187) probably result from a non-concerted biradical intermediate formed by benzyne addition to camphene.280 Benzyl-lithium adds to the aminocamphor (188) exclusively from the exo-side whereas only the competing enolization reaction occurs with more sterically hindered organometallics.281... 

This reaction occurs by an elimination/addition reaction that involves a benzyne intermediate. 

Quinoxalin-2(l//)-one 4-oxide undergoes addition reactions with phenyl isocyanate and benzyne. These reactions are supposed to proceed via cycloadducts. 

A ruthenium-benzyne complex activates C-H bonds through a sequence of reductive elimination and oxidative addition reactions . ... 

In this case, two molecules of nitrogen are formed. In all cases, the benzyne goes on to perform an addition reaction to complete the remainder of the elimination/ addition sequence, which will result in an overall substitution occurring. 

Benzyne is another cycloalkyne that has been proposed as an intermediate for elimination-addition reactions ofbenzene. 

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... 

The incoming nucleophile can attack either of the carbons of the triple bond of benzyne. Protonation of the resulting anion forms the substitution product. The overall reaction is an elimination-addition reaction Benzyne is formed in an elimination reaction and immediately undergoes an addition reaction. 

A novel example of this reaction is the double benzyne addition to cyclopropenone 235 to give 236, an intermediate en route to the novel tritriptycyl cyclopropenium cation. ... 

Arynes, such as benzyne (1,2-dehydrobenzene), also undergo Diels-Alder cycloaddition reactions. Benzyne, CelTj, is a highly reactive species and can be prepared by elimination of a suitably substituted benzene derivative. It reacts in situ with various dienes such as furan, cyclopentadiene, cyclohexadiene and even benzene and naphthalene to give bicyclic or polycyclic cycloadducts (3.15). Analogous addition reactions are shown by dehydroaromatics in the pyridine and thiophene series. 

Like heptafulvene itself, its 8-cyano derivatives take part as an 8tt-component in [8+2]cyclo-addition reactions, for example with acetylenedicarboxylic esters [365] or with benzyne [368]. 

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