New Screening Protocol for Effective Green Solvents Selection of Benzamide, Salicylamide and Ethenzamide

Abstract

New protocol for screening efficient and environmentally friendly solvents was proposed and experimentally verified. The guidance for solvent selection comes from computed solubility via COSMO-RS approach. Furthermore, solute-solvent affinities computed using advanced quantum chemistry level were used as a rationale for observed solvents ranking. The screening protocol pointed out that 4-formylomorpholine (4FM) is an attractive solubilizer compared to commonly used aprotic solvents such as DMSO and DMF. This was tested experimentally by measuring the solubility of the title compounds in aqueous binary mixtures in the temperature range between 298.15 K and 313.15 K. Additional measurements were also performed for aqueous binary mixtures of DMSO and DMF. It has been found that the solubility of studied aromatic amides is very high and quite similar in all three aprotic solvents. For most aqueous binary mixtures, a significant decrease in solubility with a decrease in the organic fraction is observed, indicating that all systems can be regarded as efficient solvent-anti-solvent pairs. In the case of salicylamide dissolved in aqueous-4FM binary mixtures, a strong synergistic effect has been found leading to the highest solubility for 0.6 mole fraction of 4-FM.

Quantification of Caffeine Interactions in Choline Chloride Natural Deep Eutectic Solvents: Solubility Measurements and COSMO-RS-DARE Interpretation

“…Unfortunately, such default computations are often far from accurate, although for some systems one can observe a fairly quantitative correspondence. For example, solubility of benzamide and salicylamide [ 100 ] can be quite accurately predicted without additional parametrization in neat and binary solvents. However, estimations made for a very similar compound, ethenzamide, are much less accurate [ 101 ].…”

Intermolecular Interactions as a Measure of Dapsone Solubility in Neat Solvents and Binary Solvent Mixtures

“…In this study, the shake-flak method of solubility determination was applied. The method has been used and validated in previous work by our group on various pharmaceuticals or drug-like compounds, including sulfa drugs (sulfanilamide [ 51 ], sulfamethizole [ 49 ]), amides (nicotinamide [ 52 ], benzamide, salicylamide, and ethenzamide [ 32 ]), acetanilide derivatives (phenacetin [ 53 ]), and nutraceuticals (coumarin [ 54 ]). Based on this protocol, the solubility determination of dapsone was preceded by the construction of a calibration curve.…”

“…First principle methods utilizing quantum chemistry computations augmented with statistical analysis, such as conductor-like screening model for realistic solvents (COSMO-RS) [ 26 , 27 , 28 ], deserve special attention. In general, this method has been found to be successful in modeling various pharmaceutically relevant properties and characteristics, including solubility [ 29 , 30 , 31 , 32 ], partition coefficients [ 33 , 34 , 35 ], acid–base properties [ 36 , 37 , 38 ], and co-crystallization abilities [ 27 , 39 , 40 , 41 , 42 , 43 ]. In recent years, the application of neural networks, including deep learning, to solubility modeling has increased [ 44 , 45 , 46 ].…”

Predicting sulfanilamide solubility in the binary mixtures using a reference solvent approach

“…It is worth noting that the protocol has been previously employed for various organic compounds and validated in literature data. 19,[22][23][24][25][26][27] To determine the concentration of the saturated solutions of sulfanilamide in the considered set of solvents, the samples containing undissolved excess of active substances were incubated with mixing (60 rpm) at 25°C. The mixtures were prepared by dissolving sulfanilamide in a solvent in glass tubes (10 mL).…”