Racemisation

Racemisation, or racemization, is the process by which an optically active compound is converted into a racemic mixture, containing equal amounts of both enantiomers and thus losing net optical rotation. It occurs when stereogenic centers invert or when reversible reactions generate planar or achiral intermediates that can re-form either enantiomer.

Common mechanisms include enolization or enolate formation at alpha-carbons of carbonyl compounds, imine/enamine tautomerization, and epimerization at chiral centers. In many cases, the reaction is catalyzed by acids, bases, heat, or catalysts that promote interconversion. Substantial racemisation can occur in amino acids, sugars, and other molecules with labile stereocenters when conditions allow reversible deprotonation/reprotonation or rearrangements.

Factors that influence the rate and extent of racemisation include temperature, solvent polarity, pH, and the presence of catalytic species. Substituents near a stereogenic center, structural constraints, and the stability of potential intermediates also play important roles. In solid-state contexts, Racemisation can occur through surface-catalyzed processes or during physical aging, though typically at different rates than in solution.

Relevance and implications vary by context. In organic synthesis and pharmaceuticals, racemisation can alter biological activity, pharmacokinetics, and safety, prompting strategies to minimize it through protective groups, milder conditions, or rapid synthesis. Conversely, controlled racemisation is used in some procedures, such as racemization steps in certain resolutions or transformations. In biological systems, racemisation of amino acids can affect protein structure and function over time.