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

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. A variation of the “shake‐flask method” was developed for the straightforward determination of the lipophilicity (log P) of fluorinated compounds and is based on the relative integration of the 19F NMR peaks of a sample and an internal reference for each phase (oct=octanol). The influence of different fluorination motifs on the lipophilicity of various aliphatic alkanols and carbohydrates was determined.