Influence of Fluorination on the Conformational Properties and Hydrogen-Bond Acidity of Benzyl Alcohol Derivatives

• Published in: Chemistry : a European journal Vol. 21; no. 32; pp. 11462 - 11474
• Main Authors: Bogdan, Elena, Compain, Guillaume, Mtashobya, Lewis, Le Questel, Jean-Yves, Besseau, François, Galland, Nicolas, Linclau, Bruno, Graton, Jérôme
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 03.08.2015; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Acidity; Alcohol; Alcohols; Benzyl alcohol; benzylic alcohols; Chemistry; Computer applications; conformation analysis; Derivatives; Electrostatic properties; Fluorination; Fluorine; hydrogen-bond acidity; Hydroxyl groups; Infrared spectroscopy; Landscapes; Mathematical analysis; Quantum chemistry; Solvation; hydrogen-bond acidity; conformation analysis; benzylic alcohols; fluorine
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201501171

The effect of fluorination on the conformational and hydrogen‐bond (HB)‐donating properties of a series of benzyl alcohols has been investigated experimentally by IR spectroscopy and theoretically with quantum chemical methods (ab initio (MP2) and DFT (MPWB1K)). It was found that o‐fluorination generally resulted in an increase in the HB acidity of the hydroxyl group, whereas a decrease was observed upon o,o′‐difluorination. Computational analysis showed that the conformational landscapes of the title compounds are strongly influenced by the presence of o‐fluorine atoms. Intramolecular interaction descriptors based on AIM, NCI and NBO analyses reveal that, in addition to an intramolecular OH⋅⋅⋅F interaction, secondary CH⋅⋅⋅F and/or CH⋅⋅⋅O interactions also occur, contributing to the stabilisation of the various conformations, and influencing the overall HB properties of the alcohol group. The benzyl alcohol HB‐donating capacity trends are properly described by an electrostatic potential based descriptor calculated at the MPWB1K/6‐31+G(d,p) level of theory, provided solvation effects are taken into account for these flexible HB donors. Fluorination and hydrogen‐bond acidity: Fluorination of benzyl alcohols is shown to significantly modify their hydrogen‐bonding properties and their conformational landscapes through intramolecular OH⋅⋅⋅F, CH⋅⋅⋅F and/or CH⋅⋅⋅O interactions (see scheme). ortho‐Fluorination results in an increase in the hydrogen‐bond acidity of the hydroxyl group, whereas o,o′‐difluorination leads to a decrease in the hydrogen‐bond acidity.