**Abstract**

This chapter deals with the unusual substitution reactions in non-aprotic solvent. Selective protic solvents that are widely being accepted for nucleophilic substitution reactions not only enhance the reaction rate but also give desire for selectivity of substituted product. Protic solvents such as *tert*-alcohol, primary alcohol, ionic liquids with *tert*-alcohol and primary alcohol functionality, and biscationic ionic liquid with protic functionality were shown best result in substitution reactions. Aliphatic nucleophilic substitution significantly developed in protic reaction medium due to the hydrogen bonding interaction with leaving groups and nucleophile. The development of substitution reactions from past two decades are summarised in this book chapter.

**Keywords:** substitution reactions, nucleophilic, alcohol solvents, phase transfer catalyst
