Rate Enhancement in the Williamson Reaction

A kinetic study conducted in tetrahydrofuran solvent revealed that the reaction is first order in catalyst, first order in alkyl halide and first order in alcohol. The low energy of activation (13.9 0.5 kcal/mole)and the entropy (—26.5 1.6 eu) are consistent with the bimolecular nature of the process. Finally, the reaction rate was insensitive to stirring rate beyond that needed to maintain effective mass transfer. The preparation of a variety of unsymmetrical ethers by this method is recorded in Table 5.1. 

An explanation of the cation size and solvent effect can be found in the energy required to separate the two charges E = (qiq2)/(Dr ). This energy is related to the distance (r) between the ions and the dielectric constant of the medium (D). The separation of the charge centers (r) in the tetrabutylammonium phenoxide ion pair is larger than in the potassium phenoxide ion pair. Tetrabutylammonium phenoxide is therefore more energetic and the nucleophilic anion is more reactive. As a consequence, alkoxide anions exhibit enhanced reactivity under phase transfer conditions. 

Similar results have been reported using a phase transfer catalyzed alkylation where dimethyl sulfate functioned as electrophile [4]. In this case, the reaction rate was sensitive to changes in the stirring rate suggesting that the reaction may be non-catal-ytic and occurring in the polar solvent (dimethyl sulfate). 

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