Investigating the Influence of (Deoxy)fluorination on the Lipophilicity of Non-UV-Active Fluorinated Alkanols and Carbohydrates by a New log P Determination Method

Abstract

Property tuning by fluorination is very effective for a number of purposes, and currently increasingly investigated for aliphatic compounds. An important application is lipophilicity (log P) modulation. However, the determination of log P is cumbersome for non-UV-active compounds. A new variation of the shake-flask log P determination method is presented, enabling the measurement of log P for fluorinated compounds with or without UV activity regardless of whether they are hydrophilic or lipophilic. No calibration curves or measurements of compound masses/aliquot volumes are required. With this method, the influence of fluorination on the lipophilicity of fluorinated aliphatic alcohols was determined, and the log P values of fluorinated carbohydrates were measured. Interesting trends and changes, for example, for the dependence on relative stereochemistry, are reported.

Keywords: NMR spectroscopy; fluorinated carbohydrates; fluorine; fluoroalcohols; lipophilicity.

Figure 1

Principle of the log P determination method. See the Supporting Information for a detailed procedure.

Figure 2

Lipophilicity map of fluorinated alcohols. See the Supporting Information, Figure S1–S10 for detailed maps and further comments.

Figure 3

Lipophilicities of conformationally rigid cyclohexanols.

Figure 4

Lipophilicities of fluorinated carbohydrates.