S_N2 reactions-The Solvent

The rates of S_N2 reactions are strongly affected by the solvent. Protic solvents— those that contain an - OH or - NH group—are generally the worst for S_N2 reactions, while polar aprotic solvents, which are polar but don’t have an - OH

or - NH group, are the best.  Protic solvents, such as methanol and ethanol, slow down S_N2 reactions by solvation of the reactant nucleophile. The solvent molecules hydrogenbond to the nucleophile and form a cage around it, thereby lowering its energy and reactivity.

In contrast with protic solvents—which decrease the rates of S_N2 reactions by lowering the ground-state energy of the nucleophile—polar aprotic solvents increase the rates of S_N2 reactions by raising the ground-state energy of the nucleophile. Acetonitrile (CH₃CN), dimethylformamide [(CH₃)₂NCHO, abbreviated DMF-, dimethyl sulfoxide [(CH₃)₂SO, abbreviated DMSO-, and hexamethylphosphoramide {[(CH₃)₂N-₃PO, abbreviated HMPA} are particularly useful. These solvents can dissolve many salts because of their high polarity, but they tend to solvate metal cations rather than nucleophilic anions. As a result, the bare, unsolvated anions have a greater nucleophilicity and S_N2 reactions take place at correspondingly increased rates. For instance, a rate increase of 200,000 has been observed on changing from methanol to HMPA for the reaction of azide ion with 1-bromobutane.