alphadeprotonatie

Alpha deprotonation, or alphadeprotonatie, is the chemical process by which a proton is removed from the carbon atom adjacent to a carbonyl group or other electron-withdrawing substituent, forming an enolate anion or a related carbanion. The negative charge is stabilized by resonance with the carbonyl, placing electron density on the oxygen in one major contributor and on the alpha carbon in another. This makes the alpha hydrogens relatively acidic compared with ordinary alkyl hydrogens, allowing deprotonation under appropriate basic conditions.

In practice, alpha deprotonation is most common for carbonyl compounds such as ketones, aldehydes, esters, and nitriles. Bases used to promote it include lithium diisopropylamide (LDA), sodium hydride, alkoxides, and other strong non-nucleophilic bases. The choice of base, solvent, and temperature influences the outcome: bulky bases and low temperatures tend to produce the kinetically controlled enolate, while stronger bases and higher temperatures can favor the thermodynamically more substituted enolate.

Enolates produced by alpha deprotonation are versatile nucleophiles. They participate in a wide range of carbon–carbon bond-forming reactions, including aldol condensations, Claisen condensations, Michael additions, and various alkylations. Protonation of the enolate regenerates the carbonyl compound, often after workup, making alpha deprotonation a reversible step in many synthetic sequences.

Beyond synthetic chemistry, enolate-type intermediates are central to several biological processes and catalytic cycles that involve alpha-carbon deprotonation and subsequent nucleophilic attack.