ZnCl2-Catalyzed Acylation of Dextrose: Process Optimization, Kinetic Modelling and Pharmaceutical Prospects

Acylation of dextrose (D-glucose) provides a reversible strategy for modulating sugar solubility by converting the highly hydrophilic polyhydroxyl molecule into a lipophilic, water-insoluble peracetate that can be readily regenerated to the parent sugar through deacylation. This reversible acylation-deacylation approach is attractive for carbohydrate processing and serves as a versatile synthetic platform for the preparation of glycoconjugate prodrugs with improved pharmaceutical properties. In the present study, the acylation of dextrose with acetic anhydride was investigated using zinc chloride as a Lewis acid catalyst. The effects of catalyst loading (0.05-1.0 g), reaction time (5-60 min) and temperature (30-90 ºC) were independently evaluated, while dextrose conversion and α/β-D-glucose 2,3,4,5,6-pentaacetate selectivity were quantified by GC-MS. A comparative screening of four Lewis acid catalysts (AlCl3, CuCl2, FeCl3 and ZnCl2) revealed that ZnCl2 gave the best performance. Under optimized conditions it achieved 86.05% dextrose conversion with 95.57% selectivity towards the desired α-anomer. The kinetic analysis revealed that the reaction follows a second-order rate law (R2 = 0.9544) with an apparent rate constant of (3.0 ± 0.2) × 10–3 L mol–1 min–1, which is consistent with a bimolecular Lewis acid-catalyzed acylation mechanism. The progressive conversion of the kinetically favoured β-anomer towards the thermodynamically more stable α-anomer supports the role of Lewis acid catalysis in promoting anomeric equilibration.