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. 2022 May 4;22(5):3343-3358.
doi: 10.1021/acs.cgd.2c00153. Epub 2022 Apr 13.

Probing the Electronic Properties and Interaction Landscapes in a Series of N-(Chlorophenyl)pyridinecarboxamides

John F Gallagher  1 , Niall Hehir  1 , Pavle Mocilac  1 , Chloé Violin  1 , Brendan F O'Connor  2 , Emmanuel Aubert  3 , Enrique Espinosa  3 , Benoît Guillot  3 , Christian Jelsch  3
Affiliations

Probing the Electronic Properties and Interaction Landscapes in a Series of N-(Chlorophenyl)pyridinecarboxamides

John F Gallagher et al. Cryst Growth Des. .

Abstract

A 3 × 3 isomer grid of nine N-(chlorophenyl)pyridinecarboxamides (NxxCl) is reported with physicochemical studies and single crystal structures (Nx = pyridinoyl moiety; xCl = aminochlorobenzene ring; x = para-/meta-/ortho-), as synthesized by the reaction of the substituted p-/m-/o-pyridinecarbonyl chlorides (Nx) with p-/m-/o-aminochlorobenzenes (xCl). Several of the nine NxxCl crystal structures display structural similarities with their halogenated NxxX and methylated NxxM relatives (x = p-/m-/o-substitutions; X = F, Br; M = methyl). Indeed, five of the nine NxxCl crystal structures are isomorphous with their NxxBr analogues as the NpmCl/Br, NpoCl/Br, NmoCl/NmoBr, NopCl/Br, and NooCl/Br pairs. In the NxxCl series, the favored hydrogen bonding mode is aggregation by N-H···Npyridine interactions, though amide···amide intermolecular interactions are noted in NpoCl and NmoCl. For the NoxCl triad, intramolecular N-H···Npyridine interactions influence molecular planarity, whereas NppCl·H2O (as a monohydrate) exhibits O-H···O, N-H···O1W, and O1W-H···N interactions as the primary hydrogen bonding. Analysis of chlorine-containing compounds on the CSD is noted for comparisons. The interaction environments are probed using Hirshfeld surface analysis and contact enrichment studies. The melting temperatures (T m) depend on both the lattice energy and molecular symmetry (Carnelley's rule), and the melting points can be well predicted from a linear regression of the two variables. The relationships of the T m values with the total energy, the electrostatic component, and the strongest hydrogen bond components have been analyzed.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
A view of [NppCl·H2O]2 linked by an O1W–H2W···O1 interaction.
Figure 2
Figure 2
A view of the C–H···O1=C1 interactions in NpmCl.
Figure 3
Figure 3
Crystallographic autostereogram of the 1D amide···amide chains along the c axis in NpoCl (atoms drawn as van der Waals spheres).
Figure 4
Figure 4
Crystallographic autostereogram of the amideN–H···Npyridinezig-zag chains in NmpCl.
Figure 5
Figure 5
Crystallographic autostereogram showing the 1D zig-zag N–H···N chains as linked by C–H···O interactions in NmmCl.
Figure 6
Figure 6
Molecular structure and intramolecular hydrogen bonding in NooCl.
Figure 7
Figure 7
ATR-IR spectra of the NxpCl triad.
Figure 8
Figure 8
Melting point in the isomers classified according to descriptor CXY derived from Carnelley’s rule: CXY = 1 when x or y is p (para), CXY = 0 (remainder).
Figure 9
Figure 9
Double linear regression of the melting point Tm on the Carnelley molecule symmetry descriptor CXY and the Eelec-EHB value, the electrostatic lattice energy diminished by the strongest hydrogen-bond electrostatic energy.
Figure 10
Figure 10
The components of the total lattice interaction energy of the NxxCl molecules computed on a cluster of surrounding molecules with CrystalExplorer using CE-B3LYP. B3LYP/6-31G(d,p) electron densities. In the summation of E_tot values, the electrostatic, polarization, dispersion, and repulsion components were scaled (coefficients 1.057, 0.74, 0.871, and 0.618) according to benchmarked energy models.
Figure 11
Figure 11
Scatterplot of total and electrostatic energy from CrystalExplorer.
Figure 12
Figure 12
The potential energy surface (PES) conformational analysis for the NxxCl isomers optimized in the gas phase: the equivalent solid-state angle is depicted by (·). Transition states (TS) and global minima (GM) are indicated and labeled. Enlarged high-resolution figures are provided in the Supporting Information.
Figure 13
Figure 13
Contact proportions in the nine NxxCl isomer crystals.
Scheme 1
Scheme 1. The NxxCl Series of Molecules with Nx Representing the C5H4NC=O (Pyridinoyl) and xCl the −HNC6H4Cl (Aminochlorobenzene) Moieties (x = Para-/Meta-/Ortho-substitutions)
The numbering scheme as used in the interplanar calculations (non-H atoms only) and Figures 1–6 is shown.
Scheme 2
Scheme 2. Intermolecular Hydrogen Bonding in NppCl·H2O and NmpCl and Intramolecular Hydrogen Bonding in NopCl
Scheme 3
Scheme 3. Possible Conformations of NxxCl as Applied to the Ortho-/Meta-substitutions
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