organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890

(2,6-Di­fluoro­phen­yl)(4-methyl­piperidin-1-yl)methanone

aSchool of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia, bSchool of Chemical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia, and cX-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia
*Correspondence e-mail: hkfun@usm.my

(Received 5 August 2011; accepted 19 August 2011; online 27 August 2011)

In the title compound, C13H15F2NO, the piperidine ring adopts a chair conformation. The dihedral angle between the least-squares plane of the piperidine ring and the benzene ring is 48.75 (7)°. In the crystal structure, the mol­ecules are connected via C—H⋯O hydrogen bonds, forming a zigzag chain along the b axis.

Related literature

For the biological applications of piperidine derivatives, see: Waelbroeck et al. (1992[Waelbroeck, M., Camus, J., Tastenoy, M. & Christophe, J. (1992). Br. J. Pharmacol. 105, 97-102.]); El Hadri et al. (1995[El Hadri, A., Maldivi, P., Leclerc, G. & Rocher, J.-P. (1995). Bioorg. Med. Chem. 3, 1183-1201.]). For puckering parameters, see: Cremer & Pople (1975[Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354-1358.]).

[Scheme 1]

Experimental

Crystal data
  • C13H15F2NO

  • Mr = 239.26

  • Monoclinic, P 21 /c

  • a = 9.1807 (7) Å

  • b = 10.9910 (8) Å

  • c = 13.2477 (8) Å

  • β = 115.582 (4)°

  • V = 1205.71 (15) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.10 mm−1

  • T = 296 K

  • 0.43 × 0.38 × 0.19 mm

Data collection
  • Bruker APEXII DUO CCD area-detector diffractometer

  • Absorption correction: multi-scan (SADABS; Bruker, 2009[Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.956, Tmax = 0.981

  • 11030 measured reflections

  • 3513 independent reflections

  • 2617 reflections with I > 2σ(I)

  • Rint = 0.018

Refinement
  • R[F2 > 2σ(F2)] = 0.045

  • wR(F2) = 0.136

  • S = 1.06

  • 3513 reflections

  • 155 parameters

  • H-atom parameters constrained

  • Δρmax = 0.23 e Å−3

  • Δρmin = −0.20 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
C3—H3A⋯O1i 0.93 2.35 3.2646 (18) 168
Symmetry code: (i) [-x, y+{\script{1\over 2}}, -z+{\script{1\over 2}}].

Data collection: APEX2 (Bruker, 2009[Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2009[Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]).

Supporting information


Comment top

The piperidine nucleus is present in a wide range of biologically active compounds. For example, the binding properties of 4-diphenyl acetoxy-N-methylpiperidine methiodide (4-DAMP) and its analogs have been evaluated on muscarinic receptors in human neuroblastoma NB-OK1 cells (M1 receptor subtype), rat heart (M2 subtype), rat pancreas (M3 subtype) and the putative M4 receptor subtype in striatum (Waelbroeck et al., 1992). NMDA receptor antagonist properties of piperidine-2-carboxylic acid derivatives have also been reported (El Hadri et al., 1995). Due to their biological importance of piperidine derivatives, herein, we have present the crystal structure of the title compound (I).

The molecular structure of the title compound is shown in Fig. 1. The piperidine (N1/C8–C12) ring adopts a chair conformation [puckering parameters: Q = 0.5569 (14) Å, θ = 2.24 (14)° and ϕ = 132 (4)° (Cremer & Pople, 1975)] with atoms C8 and C10 deviating by 0.230 (1) and 0.238 (1) Å from the least-squares plane defined by the remaining atoms (N1/C9/C11–C12) in the ring. The dihedral angle between the least-squares plane of the piperidine (N1/C8–C12) ring and the fluoro-subsituted benzene (C1–C6) ring is 48.75 (7)°.

In the crystal structure, the molecules are connected via C—H···O hydrogen bonds (Table 1) forming one-dimensional supramolecular chains along the b axis (Fig. 2).

Related literature top

For the biological applications of piperidine derivatives, see: Waelbroeck et al. (1992); El Hadri et al. (1995). For puckering parameters, see: Cremer & Pople (1975).

Experimental top

In a round bottom flask, 25ml of toluene was mixed with 4-methylpiperidine (0.01 mol, 1.0 g) with stirring. Drops of 2,6-difluorobenzylchloride (0.01 mol, 1.7g) dissolved in toluene was then added. The reaction mixture was refluxed for 30 min. The yellow precipitate formed was washed with chloroform and with water. The precipitate was then dissolved in methanol at room temperature. After few days, colourless needle-shaped crystals were formed by slow evaporation.

Refinement top

All H atoms were positioned geometrically (C—H = 0.93–0.97 Å) and were refined using a riding model, with Uiso(H) = 1.2 or 1.5Ueq(C). A rotating group model was used for the methyl group.

Computing details top

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound, showing 50% probability displacement ellipsoids and the atom-numbering scheme.
[Figure 2] Fig. 2. The crystal packing of the title compound, viewed along the c axis. Dashed lines represent C—H···O hydrogen bonds.
(2,6-Difluorophenyl)(4-methylpiperidin-1-yl)methanone top
Crystal data top
C13H15F2NOF(000) = 504
Mr = 239.26Dx = 1.318 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 4002 reflections
a = 9.1807 (7) Åθ = 2.5–29.6°
b = 10.9910 (8) ŵ = 0.10 mm1
c = 13.2477 (8) ÅT = 296 K
β = 115.582 (4)°Block, colourless
V = 1205.71 (15) Å30.43 × 0.38 × 0.19 mm
Z = 4
Data collection top
Bruker APEXII DUO CCD area-detector
diffractometer
3513 independent reflections
Radiation source: fine-focus sealed tube2617 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.018
ϕ and ω scansθmax = 30.1°, θmin = 2.5°
Absorption correction: multi-scan
(SADABS; Bruker, 2009)
h = 1212
Tmin = 0.956, Tmax = 0.981k = 1315
11030 measured reflectionsl = 1818
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)] = 0.045Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.136H-atom parameters constrained
S = 1.06 w = 1/[σ2(Fo2) + (0.0678P)2 + 0.1308P]
where P = (Fo2 + 2Fc2)/3
3513 reflections(Δ/σ)max = 0.001
155 parametersΔρmax = 0.23 e Å3
0 restraintsΔρmin = 0.20 e Å3
Crystal data top
C13H15F2NOV = 1205.71 (15) Å3
Mr = 239.26Z = 4
Monoclinic, P21/cMo Kα radiation
a = 9.1807 (7) ŵ = 0.10 mm1
b = 10.9910 (8) ÅT = 296 K
c = 13.2477 (8) Å0.43 × 0.38 × 0.19 mm
β = 115.582 (4)°
Data collection top
Bruker APEXII DUO CCD area-detector
diffractometer
3513 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2009)
2617 reflections with I > 2σ(I)
Tmin = 0.956, Tmax = 0.981Rint = 0.018
11030 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0450 restraints
wR(F2) = 0.136H-atom parameters constrained
S = 1.06Δρmax = 0.23 e Å3
3513 reflectionsΔρmin = 0.20 e Å3
155 parameters
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
F10.26788 (12)0.67786 (9)0.26565 (7)0.0733 (3)
F20.16103 (13)0.89859 (9)0.52606 (7)0.0835 (3)
O10.23349 (12)0.59626 (9)0.48443 (8)0.0697 (3)
N10.46198 (12)0.70862 (9)0.55150 (9)0.0528 (3)
C10.19420 (13)0.77289 (11)0.28922 (9)0.0476 (3)
C20.10112 (15)0.85157 (14)0.20507 (10)0.0600 (4)
H2A0.08960.84070.13240.072*
C30.02604 (15)0.94608 (15)0.23065 (12)0.0638 (4)
H3A0.03840.99920.17440.077*
C40.04459 (16)0.96375 (14)0.33859 (12)0.0625 (4)
H4A0.00581.02830.35620.075*
C50.13981 (15)0.88297 (12)0.41937 (10)0.0517 (3)
C60.21693 (12)0.78571 (10)0.39862 (8)0.0413 (2)
C70.30603 (14)0.68901 (10)0.48395 (9)0.0455 (3)
C80.54606 (14)0.82462 (12)0.56603 (10)0.0526 (3)
H8A0.47460.88390.51390.063*
H8B0.63910.81450.55020.063*
C90.60040 (14)0.86998 (11)0.68488 (10)0.0504 (3)
H9A0.50640.88710.69810.060*
H9B0.66040.94510.69460.060*
C100.70612 (14)0.77668 (11)0.76970 (10)0.0503 (3)
H10A0.80250.76360.75700.060*
C110.61572 (15)0.65643 (11)0.74973 (11)0.0563 (3)
H11A0.68640.59530.79970.068*
H11B0.52380.66600.76700.068*
C120.55722 (17)0.61347 (11)0.62987 (11)0.0631 (4)
H12A0.64930.59250.61560.076*
H12B0.49150.54110.61850.076*
C130.7612 (2)0.82022 (17)0.88950 (12)0.0781 (5)
H13A0.82410.89310.90090.117*
H13B0.82580.75830.94020.117*
H13C0.66860.83680.90310.117*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0883 (6)0.0761 (6)0.0598 (5)0.0042 (5)0.0360 (4)0.0189 (4)
F20.1137 (8)0.0920 (7)0.0538 (5)0.0326 (6)0.0448 (5)0.0010 (4)
O10.0689 (6)0.0515 (5)0.0607 (6)0.0175 (4)0.0017 (4)0.0058 (4)
N10.0477 (5)0.0406 (5)0.0503 (5)0.0007 (4)0.0025 (4)0.0013 (4)
C10.0445 (5)0.0567 (7)0.0384 (5)0.0074 (5)0.0147 (4)0.0065 (4)
C20.0545 (7)0.0820 (9)0.0331 (5)0.0143 (6)0.0091 (5)0.0061 (5)
C30.0429 (6)0.0752 (9)0.0575 (7)0.0000 (6)0.0069 (5)0.0263 (7)
C40.0511 (6)0.0641 (8)0.0702 (8)0.0153 (6)0.0243 (6)0.0146 (6)
C50.0520 (6)0.0601 (7)0.0439 (6)0.0077 (5)0.0214 (5)0.0032 (5)
C60.0380 (5)0.0456 (5)0.0350 (5)0.0021 (4)0.0107 (4)0.0002 (4)
C70.0495 (6)0.0409 (5)0.0364 (5)0.0022 (4)0.0093 (4)0.0035 (4)
C80.0447 (5)0.0528 (7)0.0501 (6)0.0060 (5)0.0110 (5)0.0037 (5)
C90.0463 (6)0.0418 (6)0.0578 (7)0.0074 (5)0.0175 (5)0.0042 (5)
C100.0443 (5)0.0553 (7)0.0446 (6)0.0016 (5)0.0130 (4)0.0039 (5)
C110.0523 (6)0.0473 (6)0.0547 (7)0.0042 (5)0.0094 (5)0.0074 (5)
C120.0613 (7)0.0417 (6)0.0580 (7)0.0084 (5)0.0009 (6)0.0013 (5)
C130.0974 (12)0.0762 (10)0.0507 (8)0.0106 (9)0.0224 (8)0.0110 (7)
Geometric parameters (Å, º) top
F1—C11.3522 (15)C8—H8A0.9700
F2—C51.3518 (14)C8—H8B0.9700
O1—C71.2192 (15)C9—C101.5213 (17)
N1—C71.3381 (14)C9—H9A0.9700
N1—C81.4595 (16)C9—H9B0.9700
N1—C121.4671 (15)C10—C131.5200 (18)
C1—C21.3777 (18)C10—C111.5218 (18)
C1—C61.3795 (15)C10—H10A0.9800
C2—C31.368 (2)C11—C121.5153 (19)
C2—H2A0.9300C11—H11A0.9700
C3—C41.379 (2)C11—H11B0.9700
C3—H3A0.9300C12—H12A0.9700
C4—C51.3747 (17)C12—H12B0.9700
C4—H4A0.9300C13—H13A0.9600
C5—C61.3739 (17)C13—H13B0.9600
C6—C71.5094 (15)C13—H13C0.9600
C8—C91.5159 (17)
C7—N1—C8125.53 (10)C8—C9—C10111.36 (10)
C7—N1—C12119.81 (10)C8—C9—H9A109.4
C8—N1—C12114.19 (9)C10—C9—H9A109.4
F1—C1—C2119.69 (11)C8—C9—H9B109.4
F1—C1—C6117.24 (11)C10—C9—H9B109.4
C2—C1—C6123.06 (12)H9A—C9—H9B108.0
C3—C2—C1118.63 (12)C13—C10—C9112.18 (12)
C3—C2—H2A120.7C13—C10—C11111.45 (12)
C1—C2—H2A120.7C9—C10—C11109.32 (9)
C2—C3—C4120.94 (12)C13—C10—H10A107.9
C2—C3—H3A119.5C9—C10—H10A107.9
C4—C3—H3A119.5C11—C10—H10A107.9
C5—C4—C3117.94 (13)C12—C11—C10111.88 (12)
C5—C4—H4A121.0C12—C11—H11A109.2
C3—C4—H4A121.0C10—C11—H11A109.2
F2—C5—C6117.00 (10)C12—C11—H11B109.2
F2—C5—C4119.21 (12)C10—C11—H11B109.2
C6—C5—C4123.79 (12)H11A—C11—H11B107.9
C5—C6—C1115.62 (10)N1—C12—C11110.65 (10)
C5—C6—C7123.88 (10)N1—C12—H12A109.5
C1—C6—C7120.14 (10)C11—C12—H12A109.5
O1—C7—N1124.08 (11)N1—C12—H12B109.5
O1—C7—C6118.17 (10)C11—C12—H12B109.5
N1—C7—C6117.69 (10)H12A—C12—H12B108.1
N1—C8—C9110.03 (10)C10—C13—H13A109.5
N1—C8—H8A109.7C10—C13—H13B109.5
C9—C8—H8A109.7H13A—C13—H13B109.5
N1—C8—H8B109.7C10—C13—H13C109.5
C9—C8—H8B109.7H13A—C13—H13C109.5
H8A—C8—H8B108.2H13B—C13—H13C109.5
F1—C1—C2—C3179.14 (11)C8—N1—C7—C613.13 (19)
C6—C1—C2—C30.79 (19)C12—N1—C7—C6175.26 (11)
C1—C2—C3—C40.9 (2)C5—C6—C7—O194.43 (15)
C2—C3—C4—C50.5 (2)C1—C6—C7—O178.49 (15)
C3—C4—C5—F2179.55 (13)C5—C6—C7—N188.19 (15)
C3—C4—C5—C60.2 (2)C1—C6—C7—N198.90 (13)
F2—C5—C6—C1179.40 (11)C7—N1—C8—C9115.22 (13)
C4—C5—C6—C10.35 (19)C12—N1—C8—C956.81 (15)
F2—C5—C6—C77.40 (18)N1—C8—C9—C1056.43 (13)
C4—C5—C6—C7172.86 (12)C8—C9—C10—C13179.72 (12)
F1—C1—C6—C5179.77 (10)C8—C9—C10—C1155.56 (14)
C2—C1—C6—C50.16 (17)C13—C10—C11—C12178.83 (12)
F1—C1—C6—C76.30 (16)C9—C10—C11—C1254.25 (14)
C2—C1—C6—C7173.64 (11)C7—N1—C12—C11116.98 (13)
C8—N1—C7—O1169.65 (13)C8—N1—C12—C1155.54 (17)
C12—N1—C7—O12.0 (2)C10—C11—C12—N153.71 (16)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C3—H3A···O1i0.932.353.2646 (18)168
Symmetry code: (i) x, y+1/2, z+1/2.

Experimental details

Crystal data
Chemical formulaC13H15F2NO
Mr239.26
Crystal system, space groupMonoclinic, P21/c
Temperature (K)296
a, b, c (Å)9.1807 (7), 10.9910 (8), 13.2477 (8)
β (°) 115.582 (4)
V3)1205.71 (15)
Z4
Radiation typeMo Kα
µ (mm1)0.10
Crystal size (mm)0.43 × 0.38 × 0.19
Data collection
DiffractometerBruker APEXII DUO CCD area-detector
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2009)
Tmin, Tmax0.956, 0.981
No. of measured, independent and
observed [I > 2σ(I)] reflections
11030, 3513, 2617
Rint0.018
(sin θ/λ)max1)0.705
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.045, 0.136, 1.06
No. of reflections3513
No. of parameters155
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.23, 0.20

Computer programs: APEX2 (Bruker, 2009), SAINT (Bruker, 2009), SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C3—H3A···O1i0.93002.35003.2646 (18)168.00
Symmetry code: (i) x, y+1/2, z+1/2.
 

Footnotes

Thomson Reuters ResearcherID: A-3561-2009

Acknowledgements

NM gratefully acknowledges funding from the Malaysian Ministry of Science, Technology and Innovation, through the Malaysian Institute of Pharmaceutical and Nutraceutical R&D Initiative Grant (grant Nos. 09-05-IFN-MEB 004 and 304/PFARMASI/650512/I121). HKF and MH thank the Malaysian Government and USM for the Research University Grant (No. 1001/PFIZIK/811160). MH also thanks USM for a post-doctoral research fellowship.

References

First citationBruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.
First citationCremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358.  CrossRef CAS Web of Science
First citationEl Hadri, A., Maldivi, P., Leclerc, G. & Rocher, J.-P. (1995). Bioorg. Med. Chem. 3, 1183–1201.  CrossRef CAS PubMed Web of Science
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals
First citationWaelbroeck, M., Camus, J., Tastenoy, M. & Christophe, J. (1992). Br. J. Pharmacol. 105, 97–102.  CrossRef PubMed CAS Web of Science

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Follow Acta Cryst. E
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds