Organic fluorine mediated intermolecular interactions: insights from experimental and theoretical charge density analyses

Abstract

The significance of fluorine-mediated weak intermolecular interactions in crystal lattices has been debated over the past few decades. Structural, computational, and theoretical insights on such interactions have resulted in controversies on them. Therefore, to demonstrate the pivotal role of “organic fluorine” in guiding crystal structures, multipole modelling based experimental and theoretical charge density analyses were performed in 1-(2,3-difluorophenyl)-2-(2,5-difluorophenyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline. Further, a search on C–F⋯F–C interactions using the Cambridge structural database revealed that type I interactions are generally preferred, followed by type II and quasi-type I/II. The search highlighted the significance of C–F⋯F–C interactions in the presence and absence of strong hydrogen bonds. However, the major intermolecular interactions involving the F atoms in the title compound are found to be C–F⋯H–C and type II C–F⋯F–C. The directional nature and the sigma hole on the F atoms were depicted in terms of the deformation of the electron density maps. The topological analyses of electron densities illustrated that “organic fluorine” mediated intermolecular interactions have a closed shell type. The analysis of electrostatic potentials brought out the attractive nature of the C–F⋯F–C interaction. Thus, the salient features of weak but significant type II C–F⋯F–C interaction and C–H⋯F–C hydrogen bonds were characterized based on the quantitative and qualitative analyses of electron densities.