Mechanistic insights into the self-esterification of lactic acid under neutral and acidic conditions

•DFT study of the self-esterification of lactic acid to lactide in bulk solution.•Watson-type mechanism is likely to be operative under neutral conditions.•Under acidic conditions, an asynchronous concerted one-step pathway is favored.•Trimerization of lactic acid dimer always prevails over intramolecular cyclization.•Conflicting criteria for lactide production could be fulfilled using zeolites. Lactic acid (LA) is frequently used as the starting material for the production of biodegradable and/or bio-compatible polymers. We study several mechanisms which have been envisaged as important for the formation of lactide (LT, the cyclic diester of LA) in toluene solutions, both under neutral and acidic conditions. Quantum mechanical calculations of molecules and aggregates have been performed at the DFT level. We determine the free energies and molecular geometries of the reactants, products, the transition states, and intermediates. Among many proposed mechanisms, we confirm that, under neutral conditions, there is no promising reaction at the prevailing experimental conditions. This is to a large extent due to entropic effects. Under acidic conditions, on the other hand, both initial conversion of LA to dimers and the subsequent conversion to lactide will proceed, in particular if additional LA molecules are available (asynchronous concerted trimolecular reaction). However, to be selective towards LT, the systems should not contain an excess of LA, a condition that could be met in suitable porous media. [Display omitted]