Dissolution of caffeine crystals in a supercritical CO2–ethanol mixture: exploring an eco-friendly green solvent

Abstract

The industrial extraction of caffeine from raw coffee beans and green tea leaves is a widely recognized process. However, there is an emerging demand to substitute conventional solvents like water and halogenated ones in organic synthesis with environment-friendly alternatives, e.g. supercritical carbon dioxide (scCO₂). To explore the solvation properties of caffeine in scCO₂, we investigated the dissolution of caffeine crystals in an scCO₂–ethanol solvent mixture at varying temperature using all-atom molecular dynamics simulations. Caffeine possesses a flat molecular structure comprising a six-membered pyrimidine ring linked to a five-membered imidazole ring through a C–C covalent bond. Its crystallization occurs via π-stacking and hydrophobic interactions. Our results show that in a mixture of scCO₂ and ethanol, the dissolution process of caffeine crystals begins at the outer surface, resulting in the disruption of coplanarity and the stacking arrangement of adjacent caffeine molecules within the crystal. In the dissolved phase, the mean caffeine–caffeine interaction energy decreases drastically to a value equal to that of the molten crystal. Strong caffeine–CO₂ interactions dominate over caffeine–caffeine interactions in breaking the crystal into monomeric units in the scCO₂–ethanol solution. Alongside investigating the structure and energetics of molecular configurations, we delved into how the supercritical carbon dioxide environment influences the dynamics of caffeine molecules. Our observations revealed that the translational and rotational diffusion rates of caffeine are significantly slower compared to those of CO₂ and ethanol in the solution, primarily due to the encapsulation of caffeine monomers by solvent molecules.