18.19:
Nucleophilic Aromatic Substitution: Elimination–Addition
Unactivated halobenzenes typically do not react with nucleophiles. However, the reaction can occur under forced conditions such as using high temperatures and high pressures, or strong bases.
An isotopic labeling experiment indicates that the reaction produces two products in roughly equal amounts.
The reaction involves a benzyne intermediate with two equally reactive carbons at the ends of the triple bond that can be attacked by a nucleophile with equal probability.
The reaction initiates with an amide ion that functions as a strong base and abstracts the proton adjacent to the leaving group to form a carbanion with a localized lone pair in the sp2 orbital.
Elimination of the halide leads to an ineffective overlap between the two sp2 orbitals
The resulting triple bond in the benzyne species is very strained and highly reactive.
Subsequent addition of the amide ion at either end of the triple bond gives a carbanion, and a final protonation yields the substituted product.
18.19:
Nucleophilic Aromatic Substitution: Elimination–Addition
Simple aryl halides do not react with nucleophiles. However, nucleophilic aromatic substitutions can be forced under certain conditions, such as high temperatures or strong bases. The mechanism of substitution under such conditions involves the highly unstable and reactive benzyne intermediate. Benzyne contains equivalent carbon centers at both ends of the triple bond, each of which is equally susceptible to nucleophilic attack. This 50–50 distribution of products is confirmed through isotopic labeling. The overall mechanism follows an elimination–addition pathway. A strong base generates a carbanionic center on the ring. Next, elimination of the halide produces the benzyne intermediate, which is highly strained and therefore extremely reactive at both ends of the triple bond. Addition of the nucleophile at either end gives the product with 50–50 distribution.