Synthesis and comparative structural study of 2-(pyridin-2-yl)-1H-perimidine and its mono- and di-N-methylated analogues

A series of unsubstituted, mono- and di-N-methylated perimidines were prepared and studied by single-crystal X-ray analysis and 1H NMR spectroscopy.


Chemical context
Perimidines are fused nitrogen heterocyclic aromatics possessing equally a -electron excess and a -electron deficiency that determine their diverse reactivities as well as their unique optical and spectroscopic properties (Pozharskii et al., 2020). These compounds have attracted considerable attention over the past two decades because of their growing application in industrial chemistry (especially as dyes and pigments), as optoelectronics, in biotechnology and medicinal chemistry (Sahiba & Agarwal, 2020).

Structural commentary
The compositions and structures of the synthesized compounds were determined both by 1 H NMR spectroscopy (for assignment, see: Figs. S1-S3 in the supporting information) and single-crystal X-ray analysis. In all cases, the organic molecules occupy general positions and comprise an essentially flat perimidine system and the pyridyl ring. Depending on the number of N-substituents, the ring systems are twisted to a greater or lesser extent (Figs. 1-3). The unsubstituted molecule of 1 is almost planar with the dihedral angle between the aromatic parts as small as 1.60 (5) , while the molecules of 2 and especially 3 show notably larger interplane angles [59.39 (8) and 87.21 (9) , respectively] because of steric repulsion between the N-methyl group(s) and the pyridin-2-yl ring. The flat conformation of 1 may be stabilized by a weak intramolecular hydrogen bond between the perimidine N1-H1 donor group and the pyridyl N3 acceptor group [d(N1Á Á ÁN3) = 2.626 (2) Å , d(N1-H1) = 0.87 (2) Å , d(H1Á Á ÁN3) = 2.19 (2) Å , N1-H1Á Á ÁN3 = 110.9 (17) ] whereas in the molecular structure of 2 the pyridyl nitrogen atom participates in a weak intramolecular C12(sp 3 )-H12AÁ Á ÁN3 contact [d(H12AÁ Á ÁN3) = 2.46 (2) Å ; C12Á Á ÁN3 = 3.059 (1) Å ; C12-H12AÁ Á ÁN3 = 120.8 (18) ]. Compound 3 is a salt and its crystal consists of doubly N-methylated perimidinium cations and iodide counter-ions combined mainly through Coulombic interactions. 1 H NMR spectroscopic studies of 1-3 revealed correlations between the chemical shifts of some bands in the spectra and the mutual arrangement of the perimidine and pyridyl aromatics. In the 1 H NMR spectrum of 1 in CDCl 3 , doublets at 6.36 and 6.91 ppm arise from the j and e protons, respectively, while the other protons of the perimidine core appear as complex multiplets in the range 7.06-7.25 ppm (Fig. S1). A similar set of bands (corresponding to the same protons) with slightly different chemical shifts can be found in the 1 H NMR spectrum of 2 ( Fig. S2) whereas 1,3-dimethyl-2-(pyridin-2yl)perimidinium iodide (3) demonstrates a reduced number of resonance signals (Fig. S3) because the protons of the fused benzene rings become equivalent. The latter results from the above arrangement of the pyridyl ring almost orthogonal to the perimidine system.
For compound 1, solvent-dependent resonance signals in the 1 H NMR spectrum were detected. In DMSO-d 6 as a solvent (Fig. S4), the characteristic doublets arising from the protons j and e are now closer (6.74 and 6.79 ppm, respectively) while the integrated intensity of the signal of the N-H proton becomes lower (0.77 ppm) which may result from a weakening of the intramolecular N-HÁ Á ÁN hydrogen bond by the polar solvent.
In contrast, two types ofinteractions are found in the crystal of 2, one of which is a slipped stacking [centroid-tocentroid shift 1.645 (2)  (2) Å between the H18 atom and the centroid of the C6-C11 ring and 3.075 (2) Å between the H9 atom and the centroid of the pyridyl ring; Fig. 6]. The resulting cationic organic layers and anionic iodide layers alternate along the c axis.

Synthesis and crystallization
The title compounds were prepared as follows: 1-H-2-(pyridin-2-yl)perimidine (1). A mixture of 1,8-diaminonaphthalene (4.523 g, 28.6 mmol), pyridin-2-ylcarboxaldehyde (2.72 ml, 28.6 mmol) and sodium metabisulfite (16.317 g, 85.8 mmol) in ethanol (50 ml) was refluxed under Ar for 4 h. The reaction mixture was evaporated to dryness, washed with water and redissolved in ethanol. Keeping the resulting solution in a freezer overnight gave a red powder, which was recrystallized from methylene chloride and dried in vacuo. Yield 6 g (86%). Single crystals suitable for X-ray analysis were grown by slow evaporation of the solvent from a solution of the substance in methylene chloride.  Intermolecular contacts (Å ) in the crystal of 1,3-dimethyl-2-(pyridin-2yl)perimidinium iodide (3, only cations are presented). Displacement ellipsoids are shown at the 50% probability level.

Figure 5
Intermolecular contacts (Å ) in the crystal of 1-methyl-2-(pyridin-2yl)perimidine (2). Displacement ellipsoids are shown at the 50% probability level. 1-Methyl-2-(pyridin-2-yl)perimidine (2). To a mixture of 1 (0.250 g, 1.02 mmol), solid KOH (0.057 g, 1.02 mmol) and anhydrous K 2 CO 3 (0.141 g, 1.02 mmol) in anhydrous Ar-saturated acetonitrile methyl iodide (0.064 ml, 1.02 mmol) was added dropwise upon stirring and the resulting suspension was heated at 323 K for 3 h and then at r.t. for two days. The reaction mixture was evaporated to dryness and the crude product was purified by column chromatography (eluent hexane/ethyl acetate 1/1 v/v), recrystallized from a mixture of CH 2 Cl 2 /hexane and dried in vacuo. Yield 185 mg (70%). Single crystals suitable for X-ray analysis were grown by slow evaporation of the solvent from a solution of the substance in chloroform. 1,3-Dimethyl-2-(pyridin-2-yl)perimidinium iodide (3). This compound was isolated from the above reaction mixture (synthesis of compound 2) as a side product (15 mg). Single crystals suitable for X-ray analysis were grown by slow evaporation of the solvent from a solution of the substance in ethanol.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 1. Hydrogen atoms in the structures of 1 and 2 were located from difference electron density maps and were refined freely. In the structure of 3, hydrogen atoms were placed in calculated positions and refined using a riding model

2-(Pyridin-2-yl)-1H-perimidine (1)
Crystal data  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.

1-Methyl-2-(pyridin-2-yl)-1H-perimidine (2)
Crystal data where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.45 e Å −3 Δρ min = −0.33 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq N2 0.76302 (17)  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.