Crystal Structures of Fluorinated Pyridines from Geometrical and Energetic Perspectives

Abstract

The low melting compounds 3-fluoropyridine, 3,5-difluoropyridine, 2,3,5-trifluoropyridine, and 2,3,5,6-tetrafluoropyridine were crystallized in situ on the diffractometer and analyzed by X-ray diffraction. The comparison with pentafluoropyridine shows a consecutive dependence of the arrangement of pyridine molecules with the increasing fluorine substitution. Starting with the monosubstituted representative, the crystal packing changes stepwise from herringbone packing to parallel arrangement of the molecules in the trifluorinated pyridine and then switches back to the edge-to-face form by the perfluorinated compound. To get a deeper insight into the aggregation behavior of the flourinated pyridines, the crystal packing motives were also analyzed on the basis of ab initio quantum-chemical calculations of the intermolecular interaction energy, using the MP2/6-311G(d,p) method. This approach allows the indication of energetically rich fragments in the crystal structures, called basic structural motifs, and the very weak attractive or rather repulsive nature of F···F interactions.

Understanding of Noncovalent Interactions Involving Organic Fluorine

“…In the crystal structure analysis of fluorine [64]. b Formation of a molecular sheet down the bc-plane in 1,2,3,5-tetrafluorobenzene with utilization of C-H···F-C and C-F···F-C interactions (crystallizes in P2 1 /c) [71] substituted isoquinolines [75,76], trifluoroacetophenones [77] N-phenylmaleimides and corresponding phthalimides [78], benzonitriles [79], pyridines [80], N benzylideneanilines [81], azobenzenes [82], etc., the importance of weak C-H···F-C hydrogen bonds was observed in the absence of any strong hydrogen bond donor. Crystal packing analysis of a series of fluorine substituted isoquinolines was observed to be stabilized by mainly C-H···F hydrogen bonds along with C-F···F-C and C-F···π in the absence of any other relatively stronger intermolecular forces such as hydrogen bonding, C-H···π or π···π interactions [75,76].…”

“…Fluorobenzonitriles [79] and fluorinated pyridines [80] were crystallized by in situ crystallization, and the significance of interactions involving "organic fluorine" was studied by Merz et al The weak C-H···F along with C-H···N [78] hydrogen bond were observed in the molecular assembly of fluoro substituted benzonitriles and subsequent increase in the melting point with the sequential change in the position of fluorine (ortho-, to meta-, to para-) over the phenyl ring relative to cyano group were noticed. In case of fluorine substituted pyridines with the increase in fluorine substitution, noticeable changes in their crystal packing were discovered.…”

Intermolecular Interaction Energies in Molecular Crystals of 4-Formylcoumarin Derivatives

“…In addition to the description of the crystal packing in terms of the presence of different intermolecular interactions, based purely on the concept of geometry (distance-angle criteria), it is also very important to analyze the intermolecular interaction energies of different non-covalent interactions in the solid state in order to obtain more detailed insight into the crystalpacking [13][14][15][16] . In this regard, a series of six molecules of 4-formylcoumarin derivatives have been taken into account and calculated theoretically their lattice energies by using PIXEL approach.…”

Crystal structures of 2-chloropyridine and 2-fluoropyridine: Isostructural crystal packing or not?

“…The question of the nature of short FÁÁÁF intermolecular distances is still not fully understood, and a controversial discussion is attributed to the importance of short FÁÁÁF intermolecular distances on the non-covalent synthesis of molecular arrangements [5]. Our own studies have shown that, comparable to halogenated benzonitriles and phenols, the substitution pattern on the benzene backbone of fluoro-substituted pyridines influences the formation of packing motifs in crystal structures [6][7][8]. Noteworthy is the structural similarity between 2,4,6-trifluoropyridine, 1,3,5-trifluorobenzene and 1,3,5-triazine.…”

“…In continuation of our investigations on aggregation phenomena of small organic compounds [3,4,[6][7][8], we have performed the crystal structure of the low-melting compound 2-chloropyridine. The crystal packing of 2-chloropyridine (1) was analyzed and compared with the crystal packing of 2-fluoropyridine (2) by experimental and theoretical methods.…”