Substitution reactions solvent-assisted transition state

The relations 4- > 2-position in rate and 4- < 2-position in will apparently apply to reactions with anions, but the reverse relation is observed in piperidination, presumably due to 2-substitution being favored by hydrogen bonding in the zwitterionic transition state (cf. 47, 59, and 277) or by solvent-assisted proton removal from the intermediate complex (235). Substitutions of polychloroquino-lines (in which there is a combined effect of azine-nitrogen and unequal mutual activation of the chlorine substituents) also show 4- > 2-position in reactivity contrary statements are documented by these same references. Examples are cited below of the relation 2- > 4-position when a protonated substrate or a cyclic transition state is involved. 

It is interesting to note in the latter connection that nucleophilic substitution transition states in which there apparently is not strong delocalization of pi electron density into the substituent tend to fall into the <7 type (cf. reactions 18 and 19 of Table VIII). In set 18, there are two ortho nitro groups which apparently take up much of the pi charge (thus it is unavailable to X), whereas in set 19, the positive piperidinium center may cause (perhaps with assistance from the NH hydrogen bonding permitted by the aprotic solvent) the... 

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