10.12 : Preparation of Alcohols via Substitution Reactions

Overview

Alcohols can be synthesized from alkyl halides via nucleophilic substitution reactions. The highly polar carbon-halogen bond in the substrate makes halide a good leaving group.  The hydroxide ion or water can act as a nucleophile to take the place of halide and form an alcohol. The substitution reactions occur via two different reaction pathways, S_N1 or S_N2,  depending on the nature of carbon attached to the halide.

Primary alcohols are synthesized from primary alkyl halides, and the reaction proceeds via the S_N2 mechanism. The nucleophile attacks the halogen-bearing carbon from the side opposite to the carbon-halogen bond. However, in the presence of a strong nucleophile, a competing elimination reaction occurs as well.

Figure_1: Parallel reactions of 1-bromobutane into substitution products and elimination products (proton abstraction).

The synthesis of secondary alcohols from secondary alkyl halides via substitution reaction is not favored since a mixture of products is formed from the competing S_N2 and E2 reaction routes.

Figure_2: Parallel reactions of 2-bromo-3-methylbutane into substitution products and elimination products (proton abstraction).  

Tertiary alkyl halides undergo S_N1 reaction with a weak base such as water to produce tertiary alcohols along with alkene as a minor product due to a competing E2 elimination reaction.

Figure_3: Parallel reactions of tertiary alkyl halides to elimination and substitution products.

If a strong nucleophile like sodium hydroxide is used, the E1 reaction dominates over S_N1.

The nature of the reactant determines the stereochemistry of the product formed. If the halogen in the alkyl halide is connected to a chiral carbon, the resulting alcohol is a mixture of two enantiomers.

Figure_4: Substitution reaction over an asymmetric carbon to yield a racemic mixture of optically active alcohols as the product