The reactions of isosorbide and its epimers, isomannide and isoidide, with dimethyl carbonate have been herein investigated as easy access to bio-based products by a free-halogen
chemistry approach. Isosorbide and its epimers show a different reactivity in bimolecular
nucleophilic substitution with dimethyl carbonate (DMC). Carboxymethylation reaction
was carried out in the presence of DMC and a weak base resulting in the high-yielding
synthesis of dicarboxymethyl derivatives. Isomannide was the most reactive anydro
sugar due to the less sterically hindered exo position of the OH groups. On the other hand, methylation of isosorbide and its epimers,
conducted in the presence of a strong base and DMC, showed the higher reactivity of
the endo hydroxyl group, isoidide being the most reactive epimer. This result has been ascribed
to the neighboring effect due to the combination of the oxygen in β-position and the intramolecular hydrogen bond within the anhydro sugar structure.
Methylation reactions were also conducted in autoclave at high temperature with the
amphoteric catalyst hydrotalcite using DMC as reagent and solvent. In this case, the
reactivity of the epimers resulted quite differently with isosorbide being the most
reactive reagent possibly as a result of the structure of hydrotalcite comprising
of both acidic and basic sites. The neighboring effect was observed with good evidence
in these methylation reactions.