Conformational Mapping, Interactions, and Fluorine Impact by Combined Spectroscopic Approaches and Quantum Chemical Calculations

Abstract

Noncovalent interactions and their careful variation can be crucial in understanding molecular structures, conformational topographies, and properties. Here, we examine the fluorination impact on the structure and conformational behavior of 2-(2-fluorophenyl)ethyl alcohol (2-FPEAL) by monitoring the first individual ionization-loss-stimulated Raman spectra of the jet-cooled molecule. The comparison of two different broad-range spectra and predicted equivalents discloses two distinct structures. One possesses a folded side chain (gauche) and the other an extended chain (anti) with the terminal hydrogen atom pointing opposite or toward the fluorine side, indicating the improper previous tentative assignment of the latter. These conformers resemble and differ from the nonfluorinated analogue structures. Theoretical analyses reveal interconversion pathways of 2-FPEAL conformers during expansion and the delicate balance between attractive (C–H···F and O–H···π) and repulsive interactions. These findings show the achievements of our integrated approach, suggesting its potential for overcoming future structural challenges.