Aryl halides benzyne intermediates from

Whether or not branching occurs at an intermediate, its existence may be demonstrated by running the reaction in the presence of a reagent designed to intercept that intermediate to yield a new and characteristic product. Observations at a qualitative level can be extremely informative (e.g. formation of cyclo-adducts when aryl halides are treated with a strong base in the presence of conjugated dienes to trap a benzyne intermediate) but even more information maybe obtained from quantitative experiments, especially when product analyses are coupled with rate measurements. 

In the original process using tin amides, transmetallation formed the amido intermediate. However, this synthetic method is outdated and the transfer of amides from tin to palladium will not be discussed. In the tin-free processes, reaction of palladium aryl halide complexes with amine and base generates palladium amide intermediates. One pathway for generation of the amido complex from amine and base would be reaction of the metal complex with the small concentration of amide that is present in the reaction mixtures. This pathway seems unlikely considering the two directly observed alternative pathways discussed below and the absence of benzyne and radical nucleophilic aromatic substitution products that would be generated from the reaction of alkali amide with aryl halides. 

We take up the aryl halides in a separate chapter because they differ so much from the alkyl halides in their preparation and properties. Aryl halides as a class are comparatively unreactive toward the nucleophilic substitution reactions so characteristic of the alkyl halides. The presence of certain other groups on the aromatic ring, however, greatly increases the reactivity of aryl halides in the absence of such groups, reaction can still be brought about by very basic reagents or high temperatures. We shall find that nucleophilic aromatic substitution can follow two very different paths the bimolecular displacement mechanism for activated aryl halides and the elimination-addition mechanismy which involves the remarkable intermediate called benzyne. 

On the basis of the labeling experiment, an alternative mechanism was proposed for the substitution reaction of aryl halides with strong base-the elimination-addition mechanism. In the first step, the elimination stage, amide anion removes a proton from the carbon on the ring adjacent to the one with the halogen. The product is an unstable intermediate known as benzyne. 

As noted in Chapter 9, conventional nucleophilic substitution reactions of the type described for aliphatic compounds don t occur at sp hybrid carbon atoms. The formation of aryl cations is disfavored because they are unstable, and attack from the backside of the C-halogen bond is rendered impossible by the ring structure. So the substitution of aryl halides is much more difficult, and the mechanism of the S).j2Ar reaction is quite different, involving addition followed by elimination—a two-step process. For example, although substitution of chlorobenzene by hydroxyl ion is possible, conditions are harsh (350 °C, high pressure), and even then, yields are low. The reaction (Figure 13.13) probably involves a benzyne intermediate (see Sections 10.9 and 13.6). 

---