The solubilities of benzoic acid and fluorinated benzoic acid derivatives in dense carbon dioxide were measured at 35 °C and 55 °C to find out how much fluorination increases the solubility of organic pharmaceuticals in dense carbon dioxide. The solubilities of two higher molecular weight pharmaceuticals, triflupromazine and flufenamic acid, in dense carbon dioxide were also measured. The solubility of benzoic acid is approximately 0.2 wt% at 35 °C and 100 bar. Attaching one fluorine atom increased the solubility of benzoic acid slightly, and the solubility of 3-tluorobenzoic acid was approximately 1 wt%. The solubility of 3,4-difluorobenzoic acid was 1.3 wt% at 35 °C and 103 bar. Introduction oftrifluoromethyl-group increased the solubility significantly, and the solubility of 3-(trifluoromethyl)benzoic acid in dense carbon dioxide at 35 °C and 100 bar was approximately 7 wt%, which is almost 40 times higher than the solubility of benzoic acid in same conditions. The solubility of triflupromazine was relatively high, i.e. 4.4 wt% at 43 °C and 145 bar. Flufenamic acid was very sparingly soluble at ambient temperatures (<50 °C), and 70-80 °C was necessary to reach 1-3 wt% solubility. These experiments show that dense carbon dioxide is a feasible solvent for fluorinated pharmaceuticals and that the fluorine content of a compound can be used as a clue to find carbon dioxide soluble molecules.
Laitinen, A., Jauhiainen, O., & Aaltonen, O. (2000). Solubility of fluorinated pharmaceuticals in dense carbon dioxide. Organic Process Research and Development, 4(5), 353 - 356. https://doi.org/10.1021/op000036b