Chapter 10 Substitution Reactions of Alkyl Halides Organic Chemistry 4 th Edition Paula Yurkanis Bruice Irene Lee Case Western Reserve University Cleveland, OH ©2004, Prentice Hall What is a substitution reaction? The atom or group that is substituted or eliminated in these reactions is called a leaving group Alkyl halides have relatively good leaving groups How do alkyl halides react? RCH 2 X X= F, Cl, Br, I Nu: - + C X C Nu + X - δ + δ - δ + δ - Alternatively … Nu: - + C X C+ δ + δ - + X - C+ C Nu Because a nucleophile substitutes for the halogen, these reactions are known as nucleophilic substitution reactions The reaction mechanism which predominates depends on the following factors: • the structure of the alkyl halide • the reactivity of the nucleophile • the concentration of the nucleophile • the solvent of the reaction The Mechanism of an S N 2 Reaction Consider the kinetic of the reaction: CH 3 Br + OH – CH 3 OH + Br – Rate = k[alkyl halide][nucleophile] a second-order reaction Three Experimental Evidences Support an S N 2 Reaction Mechanism 1. The rate of the reaction is dependent on the concentration of the alkyl halides and the nucleophile 2. The rate of the reaction with a given nucleophile decreases with increasing size of the alkyl halides 3. The configuration of the substituted product is inverted compared to the configuration of the reacting chiral alkyl halide Why does the nucleophile attack from the back side? A bulky substituent in the alkyl halide reduces the reactivity of the alkyl halide: steric hindrance