Water-catalyzed racemisation of lactide

The reactions of lactide racemisation, hydrolysis, or alcoholysis in the presence of water or anhydrous alcohol have been investigated separately. A small amount of water leads to lactide racemisation, hydrolysis, or both. Water acts as a catalyst for the racemisation of lactide. The racemisation mechanism has been studied by substituting D2O instead of H2O and measuring the substituent by gas chromatography-mass spectrometry (GC-MS). The experimental results show that the hydrogen atom on a chiral carbon of lactide is substituted by a H-2 atom of D2O. The reaction of lactide with water is in good agreement with the mechanism of addition-elimination. The addition of water to the carbonyl group produces an intermediate with a pair of hydroxyls connected to a carbon atom. If a hydroxyl hydrogen atom is transferred to the ester bond (CO-O), the hydrolysis of lactide generally occurs. Any of these hydroxyls could also be dehydrated with the close methine, thus producing an enolate, and the transfer of hydrogen from the enolic hydroxyl group results in lactide racemisation. The conversion of D- or L-lactide into meso-lactide is a reversible and endothermic reaction when catalyzed by water. When lactide reacts with alcohol, its alcoholysis occurs more readily than its racemisation. (C) 2011 Elsevier Ltd. All rights reserved.