Effect of the Leaving Group and Solvent in Nucleophilic Aliphatic Substitutions Promoted by Quarternary Onium Salts

Article abstract of DOI:10.1021/jo00169a034

Rates of nucleophilic substitutions by N3^- and SCN^- (as hexadecyltributylphosphonium salts) in a series of n-octyl derivatives (C8H17X, X = Cl, Br, I, OTos, OMes) have been measured in different solvents (MeOH, Me2SO, PhCl, cyclohexane).Nucleofugacity scales are as follows: OTos > I > OMes * Br >> Cl in MeOH; I > Br > OTos > OMes > Cl in Me2SO; I > OTos* Br > OMes >> Cl in PhCl; OTos > OMes > I > Br >> Cl in cyclohexane.In the case of the methanesulfonic group, reaction rates progressively increase as the polarity and polarizability of the medium diminish: the highest rates are observed in cyclohexane, with 732- and 33-fold enhancements for MeOH and Me2SO, respectively, with N3^-, and 22- and 14-fold enhancements with SCN^-.In the case of halo derivatives the highest rates are observed in Me2SO with enhancements up to three orders of magnitude with respect to MeOH.The rate ratios in Me2SO and MeOH, expressed as log k_Me2SO/k_MeOH are OMes (1.3), OTos (1.7), Cl (2.2), Br (2.4), I (2.9); they show the anionic nature of the activated complexes and reflect an increasing polarizability (hence an increasing solvation by Me2SO) of the activated complexes on transfer from mesilate to iodide according to the reported sequence.In cyclohexane any appreciable solvation of the entering group and of the activated complex can be excluded.Therefore, the observed rates should reflect, better than in any other solvent, not only the intrinsic nucleophilicity of the entering group but also the intrinsic nucleofugacity of the leaving group.Rate variations observed in the nonprotic solvents are discussed on the basis of differences of solvation of the activated complex as a function of its polarizability and of that of the solvent.