supplementary materials


rk2416 scheme

Acta Cryst. (2013). E69, o1807    [ doi:10.1107/S1600536813030845 ]

2-Amino-6-(piperidin-1-yl)-4-p-tolyl­pyridine-3,5-dicarbo­nitrile

S. A. Inglebert, J. Kamalraja, K. Sethusankar and G. Vasuki

Abstract top

In the title compound, C19H19N5, the piperidine ring adopts a chair conformation. The pyridine ring is essentially planar, with a maximum deviation of 0.039 (2) Å for a C atom substituted with a carbonitrile group. The mean plane of the central pyridine ring makes the dihedral angles of 37.90 (14) and 56.10 (12)° with the piperidine and benzene rings, respectively. In the crystal, mol­ecules are linked via N-H...N and C-H...N hydrogen bonds, forming chains along [101], and enclosing R22(17) ring motifs. The chains are linked by further C-H...N hydrogen bonds, forming two-dimensional networks lying parallel to (10-1), and enclosing inversion dimers with R22(20) ring motifs.

Comment top

Pyridine ring system is widely distributed in nature, especially in plant kingdom. Many important alkaloids atropine from Deadly nightshade (Atropa belladonna) contains saturated pyridine nucleus. The pyridine is found to have a large number of biological activities those including antiviral, anticancer, antimicrobial, antidiabetic and antitubercular. Pyridine is also a very active neutraceutical found in the form of vitamin B3 (Chaubey & Pandeya, 2011).

The cyano groups are flipped to different sides of the pyridine plane with atoms C12 & N3 showing deviations of 0.3416 (1)Å and 0.6489 (1)Å, while atoms C11 & N4 are bent out of the pyridine plane by -0.0866 (1)Å and -0.1408 (1)Å, respectively. The pyridine ring (N1/C6–C10) forms dihedral angles of 37.90 (14)° and 56.10 (12)° with piperidine (N2/C1–C5) and phenyl ring (C13–C18).

The pyridine ring is essentially planar with a maximum deviation of -0.039 (2) Å for C7 atom. The piperidine ring adopts a chair conformation [puckering parameters (Cremer & Pople, 1975): Q = 0.579 (3)Å, θ = 172.5 (4)° and φ = 152 (3)°]. The amino group lies in the pyridine ring. The title compound exhibits the structural similarities with the reported related structure (Inglebert et al., 2011).

In the crystal, molecules are connected through the intermolecular C—H···N and N—H···N hydrogen bonds, generating a R22(17) (Bernstein et al., 1995) motif and also chain along a axis. In addition, another pair of intermolecular, C—H···N hydrogen bond link neighbouring molecules, forming an inversion dimer and generate a R22(20) ring motif (Table 1).

Related literature top

For background to pyridine derivatives and their biological activity, see: Chaubey & Pandeya (2011). For puckering parameters, see: Cremer & Pople (1975). For graph-set notation, see: Bernstein et al. (1995). For a related structure, see: Inglebert et al. (2011).

Experimental top

Initially a mixture of 4–methylbenzaldehyde (2 mmol, 0.24 g), malononitrile (3 mmol, 0.198 g), piperidine (1.5 mmol, 0.128 g) and was stirred without any solvent at room temperature. A solid appeared immediately which was dissolved in a minimum amount (3 ml) of ethanol and the solution was refluxed until completion of the reaction (monitered by TLC). The reaction mixture was cooled. Ethanol was evaporated under reduced pressure and the residue was extracted with dichloromethane (3×10ml). Evaporation of solvent left the crude solid which was subjected to silica gel column chromatography [25 : 75 / ethyl acetate : hexane] and the product was recrystallized from dichloromethane.

Refinement top

H atoms were placed in idealized positions and allowed to ride on the parent atoms,with C—H bond lengths fixed to 0.93Å (aromatic H), 0.96Å (methyl H),0.97Å (methylene H), 0.86Å (N—H) and Uiso(H) = 1.2–1.5Ueq(C,N).

Computing details top

Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. A view of the molecular structure, showing the atom numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. H atoms are presented as a small spheres of arbitrary radius.
[Figure 2] Fig. 2. The packing structure of the title compound shows two intermolecular C—H···N and N—H···N hydrogen bond to generate R22(17) motif. H atoms have been omited for clarity.
[Figure 3] Fig. 3. The packing structure of the title compound shows another pair of intermolecular C—H···N hydrogen bonds to form inversion dimer. H atoms have been omited for clarity.
2-Amino-6-(piperidin-1-yl)-4-p-tolylpyridine-3,5-dicarbonitrile top
Crystal data top
C19H19N5F(000) = 672
Mr = 317.39Dx = 1.256 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -p 2ynCell parameters from 3705 reflections
a = 14.8695 (12) Åθ = 2.8–27.5°
b = 7.7350 (6) ŵ = 0.08 mm1
c = 15.2791 (13) ÅT = 295 K
β = 107.196 (8)°Block, colourless
V = 1678.8 (2) Å30.37 × 0.30 × 0.25 mm
Z = 4
Data collection top
Bruker Kappa APEXII CCD
diffractometer
3705 independent reflections
Radiation source: fine–focus sealed tube1346 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.056
ω and φ scansθmax = 27.5°, θmin = 2.8°
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
h = 198
Tmin = 0.972, Tmax = 0.981k = 109
7726 measured reflectionsl = 1919
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.060Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.148H-atom parameters constrained
S = 0.77 w = 1/[σ2(Fo2) + (0.068P)2 + 0.0452P]
where P = (Fo2 + 2Fc2)/3
3705 reflections(Δ/σ)max < 0.001
218 parametersΔρmax = 0.18 e Å3
0 restraintsΔρmin = 0.29 e Å3
Crystal data top
C19H19N5V = 1678.8 (2) Å3
Mr = 317.39Z = 4
Monoclinic, P21/nMo Kα radiation
a = 14.8695 (12) ŵ = 0.08 mm1
b = 7.7350 (6) ÅT = 295 K
c = 15.2791 (13) Å0.37 × 0.30 × 0.25 mm
β = 107.196 (8)°
Data collection top
Bruker Kappa APEXII CCD
diffractometer
3705 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
1346 reflections with I > 2σ(I)
Tmin = 0.972, Tmax = 0.981Rint = 0.056
7726 measured reflectionsθmax = 27.5°
Refinement top
R[F2 > 2σ(F2)] = 0.060H-atom parameters constrained
wR(F2) = 0.148Δρmax = 0.18 e Å3
S = 0.77Δρmin = 0.29 e Å3
3705 reflectionsAbsolute structure: ?
218 parametersAbsolute structure parameter: ?
0 restraintsRogers parameter: ?
Special details top

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

Refinement. Refinement of F2 against ALL reflections. The weighted R–factor wR and goodness of fit S are based on F2, conventional R–factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2σ(F2) is used only for calculating R–factors(gt) etc. and is not relevant to the choice of reflections for refinement. R–factors based on F2 are statistically about twice as large as those based on F, and R–factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.18652 (19)0.6347 (4)0.1252 (2)0.0608 (9)
H1A0.20770.51890.13340.073*
H1B0.21520.66840.06190.073*
C20.2160 (2)0.7592 (4)0.1883 (3)0.0738 (10)
H2A0.28340.74990.17760.089*
H2B0.20250.87630.17330.089*
C30.1661 (3)0.7255 (4)0.2895 (3)0.0804 (11)
H3A0.17960.81900.32610.097*
H3B0.18950.61890.30830.097*
C40.0606 (2)0.7120 (4)0.3062 (2)0.0694 (9)
H4A0.03550.82410.29710.083*
H4B0.03050.67620.36890.083*
C50.0396 (2)0.5832 (4)0.24158 (19)0.0541 (8)
H5A0.02800.57350.25340.065*
H5B0.06360.47070.25160.065*
C60.03918 (17)0.6941 (3)0.08729 (18)0.0377 (6)
C70.06080 (18)0.7199 (3)0.10909 (17)0.0393 (7)
C80.09990 (17)0.7577 (3)0.03913 (17)0.0371 (6)
C90.04006 (17)0.7845 (3)0.04943 (17)0.0390 (6)
C100.05840 (18)0.7707 (3)0.06310 (18)0.0423 (7)
C110.07316 (18)0.8218 (4)0.1260 (2)0.0469 (7)
C120.1223 (2)0.7317 (4)0.2007 (2)0.0501 (7)
C130.20408 (17)0.7636 (3)0.05558 (17)0.0389 (7)
C140.25728 (18)0.6183 (3)0.09053 (18)0.0480 (7)
H140.22910.52340.10900.058*
C150.35192 (19)0.6144 (4)0.09781 (19)0.0503 (8)
H150.38650.51580.12120.060*
C160.39660 (18)0.7517 (4)0.07161 (18)0.0457 (7)
C170.34374 (19)0.8981 (4)0.04005 (19)0.0530 (8)
H170.37290.99480.02450.064*
C180.24811 (19)0.9038 (4)0.03101 (19)0.0510 (8)
H180.21371.00290.00820.061*
C190.49842 (18)0.7409 (4)0.0753 (2)0.0621 (9)
H19A0.53360.68740.13170.093*
H19B0.52240.85520.07190.093*
H19C0.50440.67340.02460.093*
N10.09533 (14)0.7257 (3)0.00185 (15)0.0435 (6)
N20.08305 (15)0.6368 (3)0.14634 (15)0.0494 (6)
N30.17316 (17)0.7510 (3)0.27279 (18)0.0718 (8)
N40.09375 (18)0.8519 (3)0.19069 (18)0.0690 (8)
N50.11881 (16)0.8013 (3)0.14709 (15)0.0639 (7)
H5C0.17850.79100.15610.077*
H5D0.09760.83100.19150.077*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0354 (18)0.091 (2)0.051 (2)0.0125 (16)0.0047 (15)0.0054 (17)
C20.0436 (19)0.088 (2)0.091 (3)0.0040 (17)0.0231 (19)0.004 (2)
C30.081 (3)0.096 (3)0.072 (3)0.000 (2)0.034 (2)0.015 (2)
C40.073 (2)0.084 (2)0.045 (2)0.0123 (18)0.0078 (18)0.0084 (17)
C50.0489 (18)0.0681 (19)0.0394 (18)0.0019 (15)0.0037 (14)0.0112 (15)
C60.0289 (15)0.0466 (15)0.0312 (16)0.0013 (12)0.0008 (12)0.0032 (13)
C70.0308 (14)0.0550 (17)0.0243 (15)0.0002 (13)0.0041 (12)0.0013 (12)
C80.0289 (14)0.0418 (15)0.0321 (15)0.0006 (12)0.0043 (12)0.0029 (12)
C90.0305 (14)0.0521 (16)0.0287 (16)0.0030 (13)0.0001 (12)0.0008 (13)
C100.0328 (15)0.0516 (16)0.0308 (16)0.0012 (13)0.0086 (13)0.0005 (13)
C110.0366 (17)0.0588 (17)0.0363 (18)0.0075 (14)0.0032 (14)0.0022 (15)
C120.0346 (16)0.073 (2)0.0365 (17)0.0008 (15)0.0006 (13)0.0015 (15)
C130.0291 (14)0.0505 (16)0.0302 (15)0.0044 (13)0.0018 (11)0.0026 (13)
C140.0348 (17)0.0562 (18)0.0464 (19)0.0003 (15)0.0018 (14)0.0069 (14)
C150.0346 (17)0.0627 (19)0.0467 (19)0.0072 (15)0.0013 (14)0.0071 (15)
C160.0298 (15)0.0728 (19)0.0286 (16)0.0015 (16)0.0005 (12)0.0051 (15)
C170.0378 (18)0.069 (2)0.048 (2)0.0125 (16)0.0066 (14)0.0023 (15)
C180.0380 (17)0.0588 (18)0.0479 (19)0.0024 (15)0.0002 (14)0.0071 (15)
C190.0348 (16)0.103 (2)0.045 (2)0.0013 (16)0.0072 (14)0.0007 (17)
N10.0292 (12)0.0603 (14)0.0322 (14)0.0019 (11)0.0043 (10)0.0048 (11)
N20.0321 (13)0.0779 (16)0.0332 (14)0.0014 (12)0.0019 (11)0.0058 (12)
N30.0418 (15)0.122 (2)0.0382 (16)0.0048 (15)0.0092 (12)0.0035 (15)
N40.069 (2)0.095 (2)0.0407 (17)0.0215 (15)0.0134 (15)0.0021 (15)
N50.0350 (13)0.1071 (19)0.0366 (15)0.0111 (13)0.0094 (11)0.0156 (14)
Geometric parameters (Å, º) top
C1—N21.476 (3)C9—C101.420 (3)
C1—C21.516 (4)C9—C111.426 (4)
C1—H1A0.9700C10—N11.315 (3)
C1—H1B0.9700C10—N51.352 (3)
C2—C31.528 (4)C11—N41.142 (3)
C2—H2A0.9700C12—N31.147 (3)
C2—H2B0.9700C13—C181.375 (3)
C3—C41.517 (4)C13—C141.388 (3)
C3—H3A0.9700C14—C151.379 (3)
C3—H3B0.9700C14—H140.9300
C4—C51.498 (4)C15—C161.374 (4)
C4—H4A0.9700C15—H150.9300
C4—H4B0.9700C16—C171.381 (4)
C5—N21.467 (3)C16—C191.501 (4)
C5—H5A0.9700C17—C181.388 (4)
C5—H5B0.9700C17—H170.9300
C6—N21.336 (3)C18—H180.9300
C6—N11.348 (3)C19—H19A0.9600
C6—C71.438 (3)C19—H19B0.9600
C7—C81.390 (3)C19—H19C0.9600
C7—C121.431 (4)N5—H5C0.8600
C8—C91.398 (3)N5—H5D0.8600
C8—C131.495 (3)
N2—C1—C2109.4 (2)C8—C9—C10117.7 (2)
N2—C1—H1A109.8C8—C9—C11123.3 (2)
C2—C1—H1A109.8C10—C9—C11119.0 (2)
N2—C1—H1B109.8N1—C10—N5117.0 (2)
C2—C1—H1B109.8N1—C10—C9123.4 (2)
H1A—C1—H1B108.2N5—C10—C9119.5 (3)
C1—C2—C3113.0 (3)N4—C11—C9175.6 (3)
C1—C2—H2A109.0N3—C12—C7175.8 (3)
C3—C2—H2A109.0C18—C13—C14118.7 (2)
C1—C2—H2B109.0C18—C13—C8122.1 (2)
C3—C2—H2B109.0C14—C13—C8119.0 (2)
H2A—C2—H2B107.8C15—C14—C13120.1 (3)
C4—C3—C2110.4 (3)C15—C14—H14120.0
C4—C3—H3A109.6C13—C14—H14120.0
C2—C3—H3A109.6C16—C15—C14122.0 (3)
C4—C3—H3B109.6C16—C15—H15119.0
C2—C3—H3B109.6C14—C15—H15119.0
H3A—C3—H3B108.1C15—C16—C17117.5 (2)
C5—C4—C3110.0 (3)C15—C16—C19121.0 (3)
C5—C4—H4A109.7C17—C16—C19121.5 (3)
C3—C4—H4A109.7C16—C17—C18121.4 (3)
C5—C4—H4B109.7C16—C17—H17119.3
C3—C4—H4B109.7C18—C17—H17119.3
H4A—C4—H4B108.2C13—C18—C17120.3 (3)
N2—C5—C4110.5 (2)C13—C18—H18119.9
N2—C5—H5A109.6C17—C18—H18119.9
C4—C5—H5A109.6C16—C19—H19A109.5
N2—C5—H5B109.6C16—C19—H19B109.5
C4—C5—H5B109.6H19A—C19—H19B109.5
H5A—C5—H5B108.1C16—C19—H19C109.5
N2—C6—N1115.3 (2)H19A—C19—H19C109.5
N2—C6—C7124.6 (2)H19B—C19—H19C109.5
N1—C6—C7120.1 (2)C10—N1—C6120.1 (2)
C8—C7—C12116.6 (2)C6—N2—C5127.2 (2)
C8—C7—C6119.3 (2)C6—N2—C1122.8 (2)
C12—C7—C6123.6 (3)C5—N2—C1109.8 (2)
C7—C8—C9119.0 (2)C10—N5—H5C120.0
C7—C8—C13121.7 (2)C10—N5—H5D120.0
C9—C8—C13119.3 (2)H5C—N5—H5D120.0
N2—C1—C2—C353.8 (3)C9—C8—C13—C14120.1 (3)
C1—C2—C3—C450.1 (4)C18—C13—C14—C151.7 (4)
C2—C3—C4—C552.2 (4)C8—C13—C14—C15173.6 (2)
C3—C4—C5—N260.4 (3)C13—C14—C15—C160.2 (4)
N2—C6—C7—C8171.4 (2)C14—C15—C16—C172.1 (4)
N1—C6—C7—C87.6 (4)C14—C15—C16—C19176.6 (3)
N2—C6—C7—C1217.2 (4)C15—C16—C17—C182.9 (4)
N1—C6—C7—C12163.8 (2)C19—C16—C17—C18175.7 (3)
C12—C7—C8—C9166.5 (2)C14—C13—C18—C170.8 (4)
C6—C7—C8—C95.6 (4)C8—C13—C18—C17174.3 (3)
C12—C7—C8—C1315.9 (4)C16—C17—C18—C131.5 (4)
C6—C7—C8—C13172.1 (2)N5—C10—N1—C6179.7 (2)
C7—C8—C9—C100.3 (3)C9—C10—N1—C61.7 (4)
C13—C8—C9—C10177.4 (2)N2—C6—N1—C10175.2 (2)
C7—C8—C9—C11179.2 (2)C7—C6—N1—C103.9 (4)
C13—C8—C9—C111.5 (4)N1—C6—N2—C5176.4 (2)
C8—C9—C10—N13.6 (4)C7—C6—N2—C52.6 (4)
C11—C9—C10—N1175.4 (2)N1—C6—N2—C19.6 (4)
C8—C9—C10—N5177.9 (2)C7—C6—N2—C1171.4 (2)
C11—C9—C10—N53.1 (4)C4—C5—N2—C6109.7 (3)
C7—C8—C13—C18127.4 (3)C4—C5—N2—C164.9 (3)
C9—C8—C13—C1855.0 (3)C2—C1—N2—C6114.6 (3)
C7—C8—C13—C1457.5 (3)C2—C1—N2—C560.3 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N5—H5C···N3i0.862.182.999 (4)160
C2—H2B···N4ii0.972.623.509 (4)153
C19—H19A···N4iii0.962.613.509 (4)156
Symmetry codes: (i) x+1/2, y+3/2, z+1/2; (ii) x, y+2, z; (iii) x1/2, y+3/2, z1/2.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N5—H5C···N3i0.862.182.999 (4)160
C2—H2B···N4ii0.972.623.509 (4)153
C19—H19A···N4iii0.962.613.509 (4)156
Symmetry codes: (i) x+1/2, y+3/2, z+1/2; (ii) x, y+2, z; (iii) x1/2, y+3/2, z1/2.
Acknowledgements top

The authors gratefully acknowledge Dr Babu Varghese, SAIF, IIT, Chennai, India, for the data collection.

references
References top

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