Benzyne mechanism compounds

Problem 11.28 How do the following observations support the benzyne mechanism (a) Compounds lacking ortho H s, such as 2,6-dimethylchlorobenzene, do not react, (t) 2,6-Dideuterobromobenzene reacts more slowly than bromobenzene. (c) o-Bromoanisole, o-CHjOC H Br, reacts with NaNH /NH, to form m-CHjOC H.NHj. 

Unactivated aryl iodides undergo the conversion Arl — ArCHj when treated with tris(diethylamino)sulfonium difluorotrimethylsilicate and a palladium catalyst.131 A number of methods, all catalyzed by palladium complexes, have been used to prepare unsymmetrical biaryls (see also 3-16). In these methods, aryl bromides or iodides are coupled with aryl Grignard reagents,152 with arylboronic acids ArB(OH)2,153 with aryltin compounds Ar-SnR3,154 and with arylmercury compounds.155 Unsymmetrical binaphthyls were synthesized by photochemically stimulated reaction of naphthyl iodides with naphthoxide ions in an SrnI reaction.156 Grignard reagents also couple with aryl halides without a palladium catalyst, by the benzyne mechanism.157 OS VI, 916 65, 108 66, 67. 

Aromatic compounds are dechlorinated by the general mechanism shown in Sch. 1. Electron transfer to a ir-antibonding orbital forms an aromatic radical anion, which then ejects Cl" to give an aromatic radical. This radical picks up a second electron to give a very basic cx-anion, which abstracts a proton either from NH3 or from a more acidic source like water, when water is present. If water is not present, then an NH2 anion can be formed. The presence of ME can lead to the formation of aminated products via the benzyne mechanism. Aminated products were formed in dry NH3 but not when water was present [24], A further reduction via radical anion formation and proton abstraction can give dihydroaromatics or tetrahydroaromatics, or dimerization may occur. In soils, both water and... 

There is one very special feature of the benzyne mechanism. The triple bond could be attacked by nucleophiles at either end. This is of no consequence when we are dealing with bromo benzene as the products would be the same, but we can make the ends of the triple bond different and then we see something interesting, ortho-Chloro aryl ethers are easy to prepare by chlorination of the ether (Chapter 22). When these compounds are treated with NaNH2 in liquid ammonia, a single amine is formed in good yield. 

An organocopper intermediate was detected by Lewin and Cohen in the reaction of / -iodotoluene with copper in a good complexing solvent (184). Analysis of protonated aliquots from a reaction performed in quinoline indicated an accumulation of />-tolylcopper to a maximum of 43% after 95 hours, at which point the iodide was consumed, and then a slow decrease to by dimerization. Other experiments also indicate the formation of an arylcopper compound in Ullmann reactions (127,141, 210). The isolation of deuterated products, presumably from the decomposition of an intermediate organocopper species in deuterated benzene and cyclohexane, suggested decomposition to free radicals (127). Decompositions of certain o-haloarylcopper intermediates by a benzyne mechanism cannot be totally excluded. The formation of a dichlorobenzene and by-products such as dibenzofuran and triphenylene from only the ortho isomer of the chloroiodobenzenes in Ullmann coupling reactions (210)... 

The ene reaction (Eq. 2) provides a nonpolar mechanism for open-chain addition of benzyne to compounds containing an allylic hydrogen atom. The implied migration of a double bond is not always apparent from the structure of the adduct. The ene reaction frequently occurs in competition with 1, 2-cycloaddition some examples are described in Refs. 1 and 2. 

As exemplified by equation (2), the Perkin condensation of o-hydroxybenzaldehydes is an important method for the synthesis of substituted coumarins. An interesting variation on this procedure has been reported recently. Heating a mixture of o-fluorobenzaldehyde, 2-thiopheneacetic acid, acetic anhydride and triethylamine affords directly the coumarin (20 equation 13) instead of the expected cinnamic acid (21). The reaction proceeds similarly with several arylacetic acids. The reaction presumably proceeds through the cinnamic acids (21). The observed product can conceivably arise by direct nucleophilic displacement involving the carboxylate or by an elimination/addition (benzyne) mechanism. The authors note that when 2-fluorobenzaldehyde is replaced by its 2-bromo analog in this reaction, the substituted cinnamic acid (22) is the major product and the corresponding coumarin (20) is obtained only in low yield. It is suggested that since it is known that fluoride is displaced more rapidly in nucleophilic aromatic substitution reactions, while bromo aromatic compounds form benzynes more rapidly, this result is consistent with a nucleophilic displacement mechanism. 

Early on, it was demonstrated that aromatic nitro compounds may form radical anions in alkaline solutions [4], with the possibilities of photochemical reactions [5]. There followed the development of the radical chain mechanism [6]. An interesting early danonstration of reaction by this mechanism was in the reaction of ort/io-halogenoanisoles with potassium amide in liquid ammonia [7]. Reaction by the benzyne mechanism gives predominantly the uiera-substituted product due to the electronic influence of the methoxy group. Howeva, with an access of potassium metal, which promotes electron transfer, the pathway predominates yielding ort/io-anisidine, as shown in Scheme 6.4. The mechanism now forms an important synthetic pathway, and this and other homolytic processes are covered in Chapters 9 and 10. 

It has been shown e that two mechanisms, elimination-addition (benzyne) and SN2 displacement, are operative in the liquid-phase hydrolysis of halogenatcd aromatic compounds. The formation of isomeric phenols as a result of the availability of the benzyne route makes the reaction of limited synthetic value. The incorporation of the copper-cuprous oxide system suppresses reaction via the benzyne route, so that the present method has general utility for the preparation of isomer-free phenols. For example, >-cresol is the only cresol formed from -bromotoluene under the conditions of this preparation. 

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.

Liittringhaus et al. 68) have isolated many interesting substances from the byproducts ( 8%) of the Bayer process. The mechanism has been fully clarified and shown to be an aryne route. When chlorobenzene or diphenylether are treated with sodium phenyl, the products are ortho metalated derivatives and benzyne. These give the same products which are formed in the industrial phenol synthesis. The most interesting compounds are 2- and 4-hydroxy biphenyl, 2,6-diphenyl- and 2,4-diphenyl-phenol l). For similar syntheses see 69). 

Cyclopentadienone is an elusive compound that has been sought for many years but with little success. Molecular orbital calculations predict that it should be highly reactive, and so it is it exists only as the dimer. The tetraphenyl derivative of this compound is to be synthesized in this experiment. This derivative is stable, and reacts readily with dienophiles. It is used not only for the synthesis of highly aromatic, highly arylated compounds, but also for examination of the mechanism of the Diels-Alder reaction itself. Tetraphenylcyclopentadienone has been carefully studied by means of molecular orbital methods in attempts to understand its unusual reactivity, color, and dipole moment. In Chapter 48 this highly reactive molecule is used to trap the fleeting benzyne to form tetraphenylnaphthalene. Indeed, this reaction constitutes evidence that benzyne does exist. 

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