Leaving groups orientation effects

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... 

Since heteroarynes are thus seen to be subject to strong orientation effects, the detection of the occurrence of the aryne mechanism and the evaluation of the extent of its participation require a special approach. Both the aryne and Sj Arl mechanisms can occur together, and variation of the leaving group on a substrate (e.g., 2-halonaphthalenes) can cause a complete shift from the aryne (2-chloro, -bromo, and -iodo) to the Sj Arl mechanism (2-fluoro) see also Section II, D, 1. 

In the discussion of electrophilic aromatic substitution (Chapter 11) equal attention was paid to the effect of substrate structure on reactivity (activation or deactivation) and on orientation. The question of orientation was important because in a typical substitution there are four or five hydrogens that could serve as leaving groups. This type of question is much less important for aromatic nucleophilic substitution, since in most cases there is only one potential leaving group in a molecule. Therefore attention is largely focused on the reactivity of one molecule compared with another and not on the comparison of the reactivity of different positions within the same molecule. 

Moreover, product formation was not the same. Dibenzyl ethylsulfonium salt 72 gave only benzyl ethyl sulfide (73) and benzyl thiocyanate 74, but no dibenzyl sulfide or ethyl thiocyanate. By contrast, the cyclic sulfonium salt 75 gave a mixture containing chiefly (80%) dihydroisothianaphthene (76) with an equivalent amount of ethyl thiocyanate (77) and a minor amount (20%) of the sulfide-thiocyanate 78. This work represents the first direct experimental information on the rate of bimolecular nucleophilic substitution and relative orientation of the benzene ring and the leaving group and it demonstrates clearly the importance of stereoelectronic effects in these reactions. 

SCHEME 4.19 Competition experiment showing the super-arming effect of a participating group at C2 in trans orientation with respect to the leaving group. Box, benzoxazolyl DMTST, dime thy l(methy lthio )sulfonium trifl ate. 

The three reflection operations identity operation, designated E, which leaves an orientation unchanged. The effects of the six possible operations of the symmetry group Cbv can be sum-mari/ed as follows ... 

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