The A Priori Design and Selection of Ionic Liquids as Solvents for Active Pharmaceutical Ingredients.

In this paper we derive a straightforward computational approach to predict the optimal ionic liquid (IL) solvent for a given compound, based on COSMO-RS calculations. These calculations were performed on 18 different active pharmaceutical ingredients (APIs) using a matrix of 210 hypothetical ILs. These results indicated that the 18 APIs could be classified into three distinct categories based on their relative hydrogen bond donating or accepting ability, with similar optimal IL solvent predictions within each class. Informed by these results, a family of strongly hydrogen bond donating ILs based on the N-alkylguanidinium cation were prepared and characterized. The solubility of the APIs in each of these classes was found to be qualitatively consistent with the predictions of the COSMO-RS model. The suitability of these novel guanidinium salts as crystallization solvents was demonstrated by the use of N-butylguanidinium bis(trifluoromethanesulfonyl)imide for the purification of crude fenofibrate using dimethylsulfoxide as an antisolvent, which resulted in good yields and excellent purities. Finally, a simple descriptor based model is proposed to suggest the best IL solvent for arbitrary APIs.

Absorption and Oxidation of Nitrogen Oxide in Ionic Liquids.

A new strategy for capturing nitrogen oxide, NO, from the gas phase is presented. Dilute NO gas is removed from the gas phase by ionic liquids under ambient conditions. The nitrate anion of the ionic liquid catalyzes the oxidation of NO to nitric acid by atmospheric oxygen in the presence of water. The nitric acid is absorbed in the ionic liquid up to approximately one mole HNO3 per mole of the ionic liquid due to the formation of hydrogen bonds. The nitric acid can be desorbed by heating, thereby regenerating the ionic liquid with excellent reproducibility. Here, time-resolved in-situ spectroscopic investigations of the reaction and products are presented. The procedure reveals a new vision for removing the pollutant NO by absorption into a non-volatile liquid and converting it into a useful bulk chemical, that is, HNO3 .

Amine-functionalized amino acid-based ionic liquids as efficient and high-capacity absorbents for CO(2).

Ionic liquids (ILs) comprised of ammonium cations and anions of naturally occurring amino acids containing an additional amine group (e.g., lysine, histidine, asparagine, and glutamine) were examined as high-capacity absorbents for CO2. An absorption capacity of 2.1 mol CO2 per mol of IL (3.5 mol CO2 per kg IL, 13.1 wt% CO2) was measured for [N66614][Lys] at ambient temperature and about 1 mol CO2 per mol of IL at 808C (under 1 bar of CO2). This demonstrated that desorption is possible under CO2-rich conditions by temperature-swing absorption; three consecutive sorption cycles were performed with the IL. The mechanistic and kinetic study of the absorption process was further substantiated by NMR spectroscopy and in situ attenuated total reflectance FTIR for [N66614][Lys] and the homologous phosphonium-based IL [P66614][Lys]. This study revealed that carbamic acid was formed with CO2 in both ILs by chemisorption; however, the amino acid­carboxyl groups on the anion played an important­but different­catalytic role for the sorption kinetics in the two ILs. The origin of the cationic effect is speculated to be correlated with the strength of the ion interactions in the two ILs.