Elimination—addition leaving-group effects

On page 284, the differing order of leaving-group effects for elimination-addition reactions promoted by organolithium compounds as opposed to those promoted by NaNH2 is described. Explain in more detail how the nature of the... 

The scope of heteroaryne or elimination-addition type of substitution in aromatic azines seems likely to be limited by its requirement for a relatively unactivated leaving group, for an adjacent ionizable substituent or hydrogen atom, and for a very strong base. However, reaction via the heteroaryne mechanism may occur more frequently than is presently appreciated. For example, it has been recently shown that in the reaction of 4-chloropyridine with lithium piperidide, at least a small amount of aryne substitution accompanies direct displacement. The ratio of 4- to 3-substitution was 996 4 and, therefore, there was 0.8% or more pyridyne participation. Heteroarynes are undoubtedly subject to orientation and steric effects which frequently lead to the overwhelming predominance of... 

The net effect of the addition/elimination sequence is a substitution of the nucleophile for the -Y group originally bonded to the acyl carbon. Thus, the overall reaction is superficially similar to the kind of nucleophilic substitution that occurs during an Sn2 reaction (Section 11.3), but the mechanisms of the two reactions are completely different. An SN2 reaction occurs in a single step by backside displacement of the Leaving group a nucleophilic acyl substitution takes place in two steps and involves a tetrahedral intermediate. 

The combination of addition and elimination reactions has the overall effect of substituting one nucleophile for another in this case, substituting an alcohol for water. The rate of these nucleophilic substitution reactions is determined by the ease with which the elimination step occurs. As a rule, the best leaving groups in nucleophilic substitutions reactions are weak bases. The most reactive of the carboxylic acid derivatives are the acyl chlorides because the leaving group is a chloride ion, which is a very weak base (ATb KT20). 

The operation of the addition-elimination route and its details are inferred from the use of several criteria which will be discussed in the order below (a) The element effect, i.e. comparison of the substitution rates of compounds which differ only in the leaving group, extended also to study of the competition of two leaving groups attached to the same or to different carbon atoms, of the same molecule, (b) The stereochemistry of the substitution, (c) The reactivity of various systems as a function of the structural parameters. The hydrogen-exchange criterion will be discussed in connection with the elimination-addition route. 

The effect of /3-methyl groups was investigated only for the cis-a-arylsulphonyl-j3-bromo- or /3-chloro-ethylenes. The 2-4- to 3-9-fold rate decrease with MeO- ion, as well as the 1-3- to 3-2-fold decrease for /3-bromo-a-p-nitrobenzenesulphonylethylene-di-n-butylamine and cyclo-hexylamine reactions, may point to a contribution of the elimination-addition route with these nucleophiles. When the elimination becomes more difficult, either for thep-methyl derivative or with a chlorine leaving group, a j8-methyl group decreases the substitution rate 20- to 84-fold with the same amines. With PhS- ion, for which other substitution routes are less probable, the rate retardation is higher (322- to 3100-fold). 

Routes (i) and (ii) differ only in the life-time of the intermediate, although the intermediate of route (i) might only be a transition state. We will see that the stereochemistry of the product and the element effect can give information on this question. Most of the evidence points to a short-lived carbanionic intermediate, but in some examples an a,j8-adduct seems essential. Since even the direct substitution is in itself an addition-elimination process involving the nucleophile and the leaving group, and since differentiation between the routes of Scheme 2 is not always possible, we will designate all routes of Scheme 2 as addition-elimination . 

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