Evaluation of the role of disordered organic fluorine in crystal packing: insights from halogen substituted benzanilides

Abstract

The determination of the crystal and molecular structures of a large number of compounds containing the C(sp 2 )-F bond has been investigated in detail in halogenated benzanilides and also in liquids, namely the fluorinated amines. It has been observed that when the fluorine atom is present in the ortho or meta position with respect to the amide functionality in benzanilides or the amino group in fluorinated amines which are liquids at room temperature, the fluorine atom exhibits positional disorder. This is associated with changes in patterns of intermolecular interactions which affect crystal packing. Furthermore, the presence of a fluorine atom on the benzanilide framework, in the presence of a heavier halogen (chloro, bromo and iodo), meta or ortho to the amide group does not eliminate the disorder associated with these molecules. In this article, we highlight the salient features present in halogenated compounds exhibiting disorder in the position of organic fluorine with concomitant changes in crystal packing. This feature is also compared with related compounds exhibiting similarity in electronic features, namely positional disorder.

Understanding of Noncovalent Interactions Involving Organic Fluorine

“…The importance of such C-H···F interactions being weak and cooperative in nature has been realized in the crystal structure analysis of fluorinated N-(2-Chloropyridin-4-yl)-N′-phenylureas ( Fig. 2.11) [87], halogenated benzanilides (fluorinated [88] and hetero halogenated with at least one side of the phenyl ring contains fluorine [88][89][90]), trifluoromethyl (-CF 3 ) substituted benzanilides [91], fluoro-N-(pyridyl)benzamides [92], fluorine-substituted benzimidazoles [93]. In the crystal packing of a series of fluorinated N-(2-Chloropyridin-4-yl)-N′-phenylureas (Fig.…”

Short C–H⋯F interactions involving the 2,5-difluorobenzene group: understanding the role of fluorine in aggregation and complex C–F/C–H disorder in a 2 × 6 isomer grid

“…1, 12 The rational difference can be accounted by the ratio of strong donor:acceptors in halobenzanilides (D:A=1:1) compared to D:A=1:2 in the (pyridine)carboxamides (N-H vs. O=C or N pyridine ). 16 The additional acceptor (whichever of O=C or N is not utilised in strong interactions) impedes molecular disorder through the formation of additional stabilizing interactions with weaker donors.…”

Energy frameworks and a topological analysis of the supramolecular features in in situ cryocrystallized liquids: tuning the weak interaction landscape via fluorination

“…48,49 In addition to this fundamental barrier for nucleation at a very low temperature, fluorinated organic compounds often suffer from orientation fixation and disorder because of high mobility in crystal nuclei and weak intermolecular interactions which dominate the crystal packing along with strong interactions. 50 So, it is very important to set up favorable conditions for which suitable single crystals can be grown and this is the grand challenge of in situ cryocrystallization of fluorine-containing organic compounds. The in situ crystallization procedure demands no solvent and no hazardous processing materials.…”