A structural systematic study of four isomers of difluoro-N-(3-pyridyl)benzamide

Abstract

The four isomers 2,4‐, (I), 2,5‐, (II), 3,4‐, (III), and 3,5‐difluoro‐N‐(3‐pyridyl)benzamide, (IV), all with formula C12H8F2N2O, display molecular similarity, with interplanar angles between the C6/C5N rings ranging from 2.94 (11)° in (IV) to 4.48 (18)° in (I), although the amide group is twisted from either plane by 18.0 (2)–27.3 (3)°. Compounds (I) and (II) are isostructural but are not isomorphous. Intermolecular N—H...O=C interactions form one‐dimensional C(4) chains along [010]. The only other significant interaction is C—H...F. The pyridyl (py) N atom does not participate in hydrogen bonding; the closest H...Npy contact is 2.71 Å in (I) and 2.69 Å in (II). Packing of pairs of one‐dimensional chains in a herring‐bone fashion occurs viaπ‐stacking interactions. Compounds (III) and (IV) are essentially isomorphous (their a and b unit‐cell lengths differ by 9%, due mainly to 3,4‐F2 and 3,5‐F2 substitution patterns in the arene ring) and are quasi‐isostructural. In (III), benzene rotational disorder is present, with the meta F atom occupying both 3‐ and 5‐F positions with site occupancies of 0.809 (4) and 0.191 (4), respectively. The N—H...Npy intermolecular interactions dominate as C(5) chains in tandem with C—H...Npy interactions. C—H...O=C interactions form R22(8) rings about inversion centres, and there are π–π stacks about inversion centres, all combining to form a three‐dimensional network. By contrast, (IV) has no strong hydrogen bonds; the N—H...Npy interaction is 0.3 Å longer than in (III). The carbonyl O atom participates only in weak interactions and is surrounded in a square‐pyramidal contact geometry with two intramolecular and three intermolecular C—H...O=C interactions. Compounds (III) and (IV) are interesting examples of two isomers with similar unit‐cell parameters and gross packing but which display quite different intermolecular interactions at the primary level due to subtle packing differences at the atom/group/ring level arising from differences in the peripheral ring‐substitution patterns.

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

“…[24][25] and together with the present study we propose that there is a substituted 2,5difluorobenzene effect, where the particular combination of pararelated 2,5-F atoms in combination with -CONHR or -NHCOR (R = C 6 H 5 ) direct the assembly of compact C-H…F interactions. Different fluorine atom combinations (as positioned on the aromatic rings) distort the aromatic ring geometry 26-27 and impact directly on both intramolecular (e.g.…”

“…1,30,36 With F 2 -25 and 25-F 2 and previous studies [23][24][25] we envisage that with careful design it should be possible to engineer more compact C-H…F interactions.…”

“…Cambridge Structural Database: ring deformation analysis 1, [24][25][26][27] We have previously studied a subset of fluorinated aromatics on the CSD and specifically di-fluorinated benzenes. 24,25 Given the paucity of data available for 2,3-, 2,5-, 3,4-difluorobenzenes in the original analysis ( Figure 5 in ref.…”

“…24,25 Given the paucity of data available for 2,3-, 2,5-, 3,4-difluorobenzenes in the original analysis ( Figure 5 in ref. 25), only the 2,4-, 2,6-and 3,5systems were assessed, with an appraisal of all six F 2 systems.…”

“…24,25 Given the paucity of data available for 2,3-, 2,5-, 3,4-difluorobenzenes in the original analysis ( Figure 5 in ref. 25), only the 2,4-, 2,6-and 3,5systems were assessed, with an appraisal of all six F 2 systems. 25 Herein, we have re-evaluated the scope of the CSD study in Table 3 and with favourable comparisons (ESI, section 4 diagrams).…”