N 1-(4-Methyl­phen­yl)piperidine-1,4-dicarboxamide

Arun M Islor; M R Jagadeesh; H M Suresh Kumar; R Ananda Kumari; Thomas Gerber; Eric Hosten; Richard Betz

doi:10.1107/S1600536812047836

. 2012 Nov 24;68(Pt 12):o3452. doi: 10.1107/S1600536812047836

N ¹-(4-Methylphenyl)piperidine-1,4-dicarboxamide

Arun M Islor ^a, M R Jagadeesh ^b, H M Suresh Kumar ^c, R Ananda Kumari ^d, Thomas Gerber ^e, Eric Hosten ^e, Richard Betz ^e,^*

PMCID: PMC3589029 PMID: 23476265

Abstract

In the title compound, C₁₄H₁₉N₃O₂, the heterocycle adopts a ¹ C ₄ conformation with the N atom being one of the flap atoms. In the crystal, classical N—H⋯O hydrogen bonds and C—H⋯O contacts connect the molecules into a three-dimensional network.

Related literature

For the pharmacological importance of piperidine and its derivatives, see: Chen et al. (2012 ▶); Boja et al. (2011 ▶); Jakubowska et al. (2012 ▶). For puckering analysis of six-membered rings, see: Cremer & Pople (1975 ▶); Boeyens (1978 ▶). For graph-set analysis of hydrogen bonds, see: Etter et al. (1990 ▶); Bernstein et al. (1995 ▶). graphic file with name e-68-o3452-scheme1.jpg

Experimental

Crystal data

C₁₄H₁₉N₃O₂
M _r = 261.32
Monoclinic,
a = 5.0102 (1) Å
b = 28.6642 (7) Å
c = 10.1131 (2) Å
β = 103.113 (1)°
V = 1414.50 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 200 K
0.42 × 0.25 × 0.11 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.966, T _max = 0.991
27256 measured reflections
3556 independent reflections
3014 reflections with I > 2σ(I)
R _int = 0.020

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.124
S = 1.06
3556 reflections
185 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.31 e Å⁻³
Δρ_min = −0.19 e Å⁻³

Data collection: APEX2 (Bruker, 2010 ▶); cell refinement: SAINT (Bruker, 2010 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 2012 ▶) and Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009 ▶).

Supplementary Material

Click here for additional data file.^{(22.2KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812047836/bg2489sup1.cif

e-68-o3452-sup1.cif^{(22.2KB, cif)}

Click here for additional data file.^{(2.2KB, cdx)}

Supplementary material file. DOI: 10.1107/S1600536812047836/bg2489Isup2.cdx

Click here for additional data file.^{(174.4KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812047836/bg2489Isup3.hkl

e-68-o3452-Isup3.hkl^{(174.4KB, hkl)}

Click here for additional data file.^{(5.5KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536812047836/bg2489Isup4.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O1ⁱ	0.834 (17)	2.128 (17)	2.9481 (13)	167.9 (15)
N3—H3A⋯O2ⁱⁱ	0.886 (18)	2.071 (18)	2.9451 (14)	168.9 (15)
N3—H3B⋯O2ⁱⁱⁱ	0.890 (17)	2.034 (17)	2.8875 (13)	160.3 (15)
C3—H3C⋯O1ⁱ	0.99	2.41	3.2987 (17)	149

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

AMI is thankful to the Department of Atomic Energy, Board for Research in Nuclear Sciences, Government of India, for a Young scientist award. JMR thanks the Principal of GMIT Davavangere for providing research facilities.

supplementary crystallographic information

Comment

Piperidine and its derivatives are ubiquitous building blocks in the synthesis of pharmaceuticals and fine chemicals (Chen et al., 2012; Boja et al., 2011, Jakubowska et al., 2012). Members of this family have found a wide range of applications in pharmacology and are used as antidepressants (e.g. Paroxetine) and analgesics (e.g. meperidine hydrochloride) or to control attention-deficit hyperactivity disorder (e.g. Methylphenidate). In view of the biological importance, the title compound was synthesized to study its crystal structure.

According to a puckering analysis (Cremer & Pople, 1975; Boeyens, 1978), the piperidine ring adopts a ¹C₄ conformation with the the nitrogen atom as well as the carbon atom in para position to it acting as the flap atoms (^N2C_C5). The primary amide group occupies an equatorial position. Due to amide-type resonance, the intracyclic nitrogen atom is present in an almost planar environment, the least-squares plane defined by the urea moiety (N2–C2–O1–N1) featuring the carbon atom as the one atom deviating most from this plane by 0.010 (1) Å (r.m.s. of all fitted atoms = 0.0057 Å). The least-squares planes through the atoms of the heterocycle and the phenyl groups define an angle of 48.15 (7) °. The planes defined by the non-hydrogen atoms of the amide groups intersect the least-squares plane defined by the intracyclic atoms of the heterocycle at angles of 29.22 (15) ° and 71.8 (2) ° with the smaller angle found for the secondary amide group (Fig. 1).

In the crystal, non-classical C–H..O bonds as well as classical hydrogen bonds of the N–H···O type coexist. The former ones take part between one of the intracyclic methylene groups directly bonded to the nitrogen atom of the piperidine moiety and the oxygen atom of the secondary amide group (which also acts as acceptor for one set of N–H···O hydrogen bonds). The hydrogen atoms of the primary amide group, in turn, link the oxygen atom of its own functional group in neighbouring molecules as acceptor. Metrical parameters as well as information about the symmetry of these contacts are summarized in Table 1. In total, these contacts connect the molecules to a three-dimensional network. According to a graph-set analysis (Etter et al., 1990; Bernstein et al., 1995), the descriptor for the C–H···O contacts is C¹₁(5) on the unitary level while the descriptor found for the hydrogen bonds fostered by the secondary amide group necessitates a C¹₁(4) on the same level. The description of the hydrogen bonding pattern created by the primary amide group is best achieved by a binary descriptor of R²₄(8). The shortest intercentroid distance between two aromatic systems corersponds to a [100] translation (Fig. 2).

Experimental

Piperidine-4-carboxamide (10.0 g, 0.078 mol) was dissolved in THF (200 ml). To this triethylamine (23.27 g, 0.23 mol) was added, followed by 1-isocyanato-4-methylbenzene (11.31 g, 0.085 mol). The reaction mixture was stirred at room temperature for 12 h. Completion of the reaction was monitored by TLC. The precipitated solid was filtered, washed with THF and dried under vacuum to get the desired product. The resulting solid was recrystallized from ethanol, yield: 18.5 g (90.77%).