The Elimination-Addition Pathway Benzyne

It subsequently became clear that the substitution reaction could be carried out even if no other substituents were present on the aromatic ring and that even less vigorous conditions could be used. As shown in Equation 7.63, bromobenzene (CeHsBr) on treatment with lithium diethylamide (A,A-diethylaminolithium [LiN(CH2CH3)2]) in A,A-diethylamine (A-ethyl-ethanamine [(CH3CH2)2NH]) solvent results in substitution of the A,A-diethylamino group for the bromine. 

In a further development, it was found (Equation 7.64) that substituents already present could affect the outcome of the reaction either by electron donation (making some positions less likely to be attacked by a nucleophile), electron withdrawal, and/ or exertion of a steric effect to block the incoming species. 

using radiolabeled ( C) bromobenzene (CeHsBr), it was shown that the aniline (aminobenzene, C6H5NH2) resulting from the reaction with sodium amide in liquid ammonia was a 1 1 mixture of ipso- and ortho-[ Ci]-anihnes (aminoben-zenes) (Equation 7.65). 

Interestingly, kinetic studies have shown that, depending on the nucleophile, the leaving group and even the solvent, either the hrst step (the addition of the nucleophile) or the second step (the loss of the leaving group) can be rate determining. 

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