Crystal structures of three N-(pyridine-2-carbonyl)pyridine-2-carboxamides as potential ligands for supramolecular chemistry

The crystal structures of three N-(pyridine-2-carbonyl)pyridine-2-carboxamide ligands, with or without F atoms on the 3-position of the pyridine ring, with potential use in supramolecular chemistry are reported.


Chemical context
N-(Pyridine-2-carbonyl)pyridine-2-carboxamide systems and their derivatives have been shown to be very useful intermediates for the construction of molecular building blocks, able to self-assemble into a wide range of super-architectures taking advantage of acceptor-donor-donor-acceptor (ADDA) arrays of hydrogen-bonding sites (Corbin et al., 2001). Further interest in this family of compounds has involved the investigation of their metal coordination complexes, which possess strong luminescence characteristics (Das et al., 2018), as well as their electrochemical (Gasser et al., 2012), magnetic (Kajiwara et al., 2010) and catalytic properties (Chowdhury et al., 2007). Consequently, the synthesis of N-(pyridine-2-carbonyl)pyridine-2-carboxamide, containing different functional groups, at a large scale and in a high yield is of great importance in the field of supramolecular chemistry. Previously reported studies have shown the conversion of 2-aminopyridine to 1 in a single step (Gerchuk & Taits, 1950;Corbin et al., 2001). However, the utilized reaction conditions were, to some extent, harsh and the reported yield of the compound was rather low (< 32%), presumably because of the inferior nucleophilicity of the -NH 2 groups at the 2-position of the pyridine rings. Moreover, the use of this procedure is limited to the synthesis of symmetrical imides. The synthesis of high-yield asymmetrical imides, bearing different functional groups on the pyridine rings, is still challenging.

Structural commentary
The structure of 1, although determined at a different temperature of 200 K, has previously been deposited in the CSD (refcode COJNAT; Castaneda & Gabidullin, 2019). Compound 1 crystallizes in the non-centrosymmetric orthorhombic space group Pna2 1 , with the asymmetric unit consisting of one N-(pyridine-2-carbonyl)pyridine-2-carboxamide molecule. The molecular structure of 1 is found almost completely planar, with a dihedral angle of 6.1 (2) between the best planes through the two pyridine rings (Fig. 1a).
The structure of 2 is isomorphous with 1, although the 3-fluoro-N-(pyridine-2-carbonyl)pyridine-2-carboxamide molecules are rotated 90 with respect to 1 (Fig. 2). Similarly to 1, the asymmetric unit contains one planar 3-fluoro-N-(pyridine-2-carbonyl)pyridine-2-carboxamide molecule, which shows a dihedral angle of 5.2 (2) between the best planes through the two pyridine rings. Here, the fluoro group is found disordered over both pyridine rings, i.e. a transverse disorder by 180 rotation along the axis through the imide N-H function occurs, showing refined occupancy factors of 0.563 (8) and 0.437 (8) for the first (F1A) and second fluoro (F1B) site, respectively (Fig. 1b) Molecular structures of (a) 1, (b) 2 and (c) 3, showing thermal displacement ellipsoids drawn at the 50% probability level and the atom-labelling scheme. The disorder in 2 (b) is shown in yellow. The carbon atoms in the asymmetric unit of 3 (c) are shown in green. Intramolecular hydrogen bonds are indicated.

Figure 2
Unit-cell fit of the structures of 1 and 2, showing a 90 rotation of the molecules of 2 (in green). Hydrogen atoms and disorder of the fluorine atoms are omitted for clarity.
Compound 3 crystallizes in the centrosymmetric monoclinic space group I2/a, with the asymmetric unit consisting of only half of a total 3-fluoro-N-(3-fluoro-pyridine-2-carbonyl)pyridine-2-carboxamide molecule. The second half is generated by symmetry, i.e. a twofold axis runs through the N-H imide atoms. In contrast to the previous structures of 1 and 2, the molecular structure of 3 is not planar, with a dihedral angle of 29.73 (11) between the best planes through the two pyridine rings (Fig. 1c).
For the structure of 2, analogous to 1, only weakinteractions are present in the crystal packing between the 3fluoro-pyridine rings, with centroid-centroid distances in the range 4.915 (3) to 5.473 (3) Å , while C OÁ Á Á contacts are also observed in the crystal packing [C6-O1Á Á ÁCg1(x, y, À1 + z)= 3.865 (4) Å ; Cg1 is the centroid of the C1-C5/N1 ring]. Analogous to 1, intramolecular potential hydrogen bonds    Packing in the structure of 2, showing (a) the perpendicularly oriented molecules, viewed down the a axis and (b) the double layers of paralleloriented (face-to-face) molecules, interchanged with analogous double layers, perpendicular to the former layers. C10-H10Á Á ÁF1A hydrogen bonds are indicated. Hydrogen atoms and disorder of the fluorine atoms are omitted for clarity. Table 1 Hydrogen-bond geometry (Å , ) for 1.  (Table 2). However, in the packing, analogous to 1, alternating double layers of parallel (face-to-face) molecules of 2 are observed, parallel with the (100) plane (Fig. 4). Hence, the extra C-HÁ Á ÁF bonds do not alter the overall architecture.

Database survey
A survey of compounds related to 1, 2 and 3, deposited with the Cambridge Structural Database (CSD 2021.1, version 5.42 updates May 2021; Groom et al., 2016) resulted in three other compounds with refcodes COJNAT, WUXQOW and ZAVVAV.

Figure 5
Packing in the structure of 3, showing (a) the longitudinal tubular arrangement of the molecules along the c axis and (b) the aromatic pyridine and the carbonyl/fluorine moieties facing towards each other. C5-H5Á Á ÁF1 and C3-H3Á Á ÁF1 hydrogen bonds are indicated. Hydrogen atoms are omitted for clarity. Table 2 Hydrogen-bond geometry (Å , ) for 2.
The structure with refcode WUXQOW (Sahu et al., 2010) represents an analogous structure to 1, but featuring quinoline moieties instead of pyridine rings, i.e. N,N-bis(quinolin-2ylcarbonyl)amine. Similarly to 1, the molecular structure is also found to be almost completely planar, with a dihedral angle of 1.34 (4) between the best planes through the two quinoline moieties.

Synthesis and crystallization
The known compound 1 was prepared in excellent yield by the reaction between 2-pyridinecarbonyl chloride and 2-pyridinecarboxamide under mild conditions. By introducing a fluoro group at the 3-position of 2-pyridinecarbonyl chloride and/or 2-pyridinecarboxamide, the new compounds 2 and 3 could be obtained, also in excellent yield. Details for the synthesis of the precursors and the products are given below. Unless otherwise stated, all reagents were used as received.

2-Pyridinecarbonyl chloride
The preparation of 2-pyridinecarbonyl chloride was performed according to a previously reported procedure (Aluri et al., 2011). 2-Pyridinecarboxylic acid (1.23 g, 10 mmol) and SOCl 2 (11.9 g, 100 mmol) were dissolved in 100 ml of dry toluene with 10 drops of DMF. The reaction mixture was refluxed at 383.15 K for 3 h. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. The resulting viscous residue was used directly in the next step without further purification.
3-Fluoropyridine-2-carbonyl chloride The preparation of 3-fluoropyridine-2-carbonyl chloride was performed according to a previously reported procedure (Aluri et al., 2011). 3-Fluoropyridin-2-carboxylic acid (1.41 g, 10 mmol) and SOCl 2 (11.9 g, 100 mmol) were dissolved in 100 ml of dry toluene with 10 drops of DMF. The reaction mixture was refluxed at 383 K for 3 h. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. The resulting viscous residue was used directly in the next step without further purification.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 4. For all structures, the imide N-H hydrogen atoms could be located from a difference electrondensity Fourier map, and were further refined with isotropic temperature factors fixed at 1.2 times U eq of the parent atoms.

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq Occ. (

3-Fluoro-N-(3-fluoropyridine-2-carbonyl)pyridine-2-carboxamide (3)
Crystal data  where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.29 e Å −3 Δρ min = −0.32 e Å −3 Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.