The functional group of the alcohols is the hydroxyl group, –OH. Unlike the alkyl halides, this group has two reactive covalent bonds, the C–O bond and the O–H bond. The electronegativity of oxygen is substantially greater than that of carbon and hydrogen.

Consequently, the covalent bonds of this functional group are polarized so that oxygen is electron rich and both carbon and hydrogen are electrophilic, as shown in the drawing on the right.

Indeed, the dipolar nature of the O–H bond is such that alcohols are much stronger acids than alkanes (by roughly 10³⁰ times), and nearly that much stronger than ethers (oxygen substituted alkanes that do not have an O–H group).

The most reactive site in an alcohol molecule is the hydroxyl group, despite the fact that the O–H bond strength is significantly greater than that of the C–C, C–H and C–O bonds, demonstrating again the difference between thermodynamic and chemical stability.

1. Substitution of the Hydroxyl Hydrogen

Alkyl substitution of the hydroxyl group leads to ethers. This reaction provides examples of both strong electrophilic substitution (first equation below), and weak electrophilic substitution (second equation).

The latter S_N2 reaction is known as the Williamson Ether Synthesis, and is generally used only with 1º-alkyl halide reactants because the strong alkoxide base leads to E2 elimination of 2º and 3º-alkyl halides.

One of the most important substitution reactions at oxygen is ester formation resulting from the reaction of alcohols with electrophilic derivatives of carboxylic and sulfonic acids.

The following illustration displays the general formulas of these reagents and their ester products, in which the R'–O– group represents the alcohol moiety. The electrophilic atom in the acid chlorides and anhydrides is colored red.