Reactivity of the Alpha-Hydrogen: Aldol Condensation

A hydrogen atom on the carbon immediately adjacent to a carbonyl group -- the $\alpha$-carbon -- behaves quite differently from an ordinary $\text{C-H}$ bond elsewhere in the molecule: it is markedly acidic (with a $\text{p}K_a$ around $19$-$20$, far more acidic than a typical alkane $\text{C-H}$ at $\text{p}K_a \approx 50$, though still much weaker than water or an alcohol). The reason is that removing this proton leaves behind a carbanion that is not localised on a single carbon at all -- it is stabilised by resonance with the adjacent carbonyl group, delocalising the negative charge onto the more electronegative oxygen as well. This resonance-stabilised species is called an enolate ion, and it can be drawn as two resonance contributors: one with the negative charge on carbon (a simple carbanion form) and one with the negative charge on the more electronegative oxygen and a new $\text{C=C}$ double bond in place of the old $\text{C=O}$ (the enolate form proper) -- the true structure is a hybrid of both, but is chemically dominated by the oxygen-centred form.

The aldol reaction. When an aldehyde or ketone possessing at least one $\alpha$-hydrogen is treated with dilute aqueous base (typically $\text{NaOH}$) at room temperature, the base removes an $\alpha$-hydrogen to generate the enolate ion described above. This enolate is itself a nucleophile (its carbanion-like $\alpha$-carbon carries substantial negative character), and it attacks the electrophilic carbonyl carbon of a second molecule of the aldehyde or ketone, exactly as any other nucleophile would in §8.5. The result, after protonation of the resulting alkoxide, is a single new molecule containing both a hydroxyl group and a carbonyl group, positioned $\beta$ and unreacted-carbonyl respectively -- a $\beta$-hydroxy-aldehyde (an 'aldol', from ald-ehyde + alcoh-ol) if the starting material was an aldehyde, or a $\beta$-hydroxy-ketone if it was a ketone. For example, two molecules of acetaldehyde combine under dilute base to give 3-hydroxybutanal, $\text{CH}_3\text{CH(OH)CH}_2\text{CHO}$. …