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

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ISSN: 2056-9890

2,4-Di­chloro-6-(piperidin-1-ylmeth­yl)phenol

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aDivision of Natural Science, Osaka Kyoiku University, Kashiwara, Osaka 582-8582, Japan, bDepartment of Chemistry and Biology Engineering, Fukui National College of Technology, Sabae, Fukui 916-8507, Japan, and cDivision of Material Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192, Japan
*Correspondence e-mail: kubono@cc.osaka-kyoiku.ac.jp

(Received 26 September 2005; accepted 10 October 2005; online 15 October 2005)

In the title compound, C12H15Cl2NO, the piperidine ring adopts a chair conformation. An intra­molecular O—H⋯N hydrogen bond is observed. The packing of the mol­ecules in the crystal structure is stabilized by ππ inter­actions and Cl⋯Cl contacts.

Comment

The pharmacological properties of piperidine derivatives have led to many studies of the design and synthesis of these compounds (Hu et al., 2002[Hu, X. E., Kim, N. K., Ledoussal, B. & Colson, A.-O. (2002). Tetrahedron Lett. 43, 4289-4293.]; Walker et al., 2005[Walker, S. M., Williams, J. T., Russell, A. G. & Snaith, J. S. (2005). Tetrahedron Lett. 46, 6611-6615.]). In addition, a number of these derivatives can act as complexing reagents with metal ions. We have previously studied the application of amino­phenol derivatives as ion size recognition reagents (Hirayama et al., 2001[Hirayama, N., Horita, Y., Oshima, S., Kubono, K., Kokusen, H. & Honjo, T. (2001). Talanta, 53, 857-862.]), and in this work, describe the crystal structure of 2,4-dichloro-6-(piperidin-1-ylmeth­yl)phenol, (I)[link], which would be expected to act as an effective chelating reagent.

[Scheme 1]

Compound (I)[link] crystallizes in the monoclinic space group P21/c, with one mol­ecule in the asymmetric unit. The bond lengths and angles observed in the piperidylmethyl group are all in the normal ranges and comparable with those of other related compounds (Deng et al., 2001[Deng, X., Guo, Y.-M., Du, M. & Fang, Y.-Y. (2001). Acta Cryst. E57, o488-o489.]; Yuan et al., 2004[Yuan, D., Zhang, M., Pan, Z. & Ma, P. (2004). Acta Cryst. E60, o1321-o1322.]). The piperidine ring adopts the usual chair conformation. The torsion angles C1—C6—C7—N1 and C5—C6—C7—N1 are 44.20 (18) and −139.28 (14)°, respectively. There is an intra­molecular O—H⋯N hydrogen bond (Table 2[link]).

In the crystal structure, the shortest inter­molecular C⋯C contact distance is 3.533 (2) Å for C4⋯C6i [symmetry code: (i) −x, −y, −z]. In addition, weak inter­molecular Cl⋯Cl contacts are observed. The contact distances Cl1⋯Cl1ii and Cl1⋯Cl2iii are 3.4596 (6) and 3.5734 (6) Å, respectively [symmetry code: (ii) −x, −y, 1 − z; (iii) x, −[{1\over 2}]y, [{1\over 2}] + z]. The packing of the mol­ecules in the crystal structure is stabilized by ππ inter­actions and Cl⋯Cl contacts between dichloro­benzene groups.

[Figure 1]
Figure 1
A view of the mol­ecule of (I)[link], showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are represented by circles of arbitrary size. The dashed line indicates the O—H⋯N hydrogen bond.
[Figure 2]
Figure 2
The packing of the mol­ecules of (I)[link], viewed down the a axis, with Cl⋯Cl contacts shown as dashed lines.

Experimental

Compound (I)[link] was prepared by the Mannich reaction. 2,4-Dichloro­phenol (6.52 g, 40 mmol), piperidine (3.41 g, 40 mmol) and paraformaldehyde (1.20 g, 40 mmol) in methanol (80 ml) were refluxed for 6 h. The mixture was cooled to room temperature, then the solvent was evaporated under vacuum. The resulting oil was extracted with chloro­form and evaporated to yield a solid. The product was recrystallized from methanol to give colourless crystals suitable for X-ray analysis. Yield 52.6%; m.p. 335.0–335.4 K. Analysis calculated for C12H15Cl2NO: C 55.40, H 5.81, N 5.38%; found: C 55.49, H 5.87, N 5.37%. 1H NMR (CDCl3, p.p.m., 400 MHz): 1.46–1.69 (m, 6H, CH2), 2.53 (brs, 4H, CH2), 3.65 (s, 2H, CH2), 6.85 (d, J = 2.5 Hz, 1H, ArH), 7.24 (d, J = 2.5 Hz, 1H, ArH), 10.2 (brs, 1H, OH).

Crystal data
  • C12H15Cl2NO

  • Mr = 260.15

  • Monoclinic, P 21 /c

  • a = 9.571 (4) Å

  • b = 11.794 (4) Å

  • c = 11.345 (5) Å

  • β = 95.89 (3)°

  • V = 1273.9 (9) Å3

  • Z = 4

  • Dx = 1.356 Mg m−3

  • Mo Kα radiation

  • Cell parameters from 25 reflections

  • θ = 15.5–17.1°

  • μ = 0.49 mm−1

  • T = 298.1 K

  • Prism, colourless

  • 0.50 × 0.20 × 0.20 mm

Data collection
  • Rigaku AFC-7R diffractometer

  • ω–2θ scans

  • Absorption correction: none

  • 3619 measured reflections

  • 2937 independent reflections

  • 2773 reflections with F2 > 2σ(F2)

  • Rint = 0.026

  • θmax = 27.5°

  • h = −12 → 12

  • k = −15 → 0

  • l = −8 → 14

  • 3 standard reflections every 150 reflections intensity decay: 2.4%

Refinement
  • Refinement on F2

  • R[F2 > 2σ(F2)] = 0.039

  • wR(F2) = 0.133

  • S = 1.01

  • 2776 reflections

  • 160 parameters

  • H-atom parameters constrained

  • w = 1/[0.0034Fo2 + 1σ(Fo2)]/(4Fo2)

  • (Δ/σ)max < 0.001

  • Δρmax = 0.29 e Å−3

  • Δρmin = −0.52 e Å−3

Table 1
Selected geometric parameters (Å, °)[link]

O1—C1 1.3559 (19)
N1—C7 1.474 (2)
N1—C8 1.466 (2)
N1—C12 1.472 (2)
C2⋯C5i 3.609 (2)
C4⋯C6i 3.533 (2)
Cl1⋯Cl1ii 3.4596 (17)
Cl1⋯Cl2iii 3.5734 (17)
C7—N1—C8 110.88 (12)
C7—N1—C12 111.67 (12)
C8—N1—C12 110.63 (12)
N1—C7—C6 111.09 (12)
N1—C8—C9 111.12 (14)
N1—C12—C11 109.91 (14)
Symmetry codes: (i) -x, -y, -z; (ii) -x, -y, -z+1; (iii) [+x, -y-{\script{1\over 2}}, +z+{\script{1\over 2}}].

Table 2
Hydrogen-bond geometry (Å, °)[link]

D—H⋯A D—H H⋯A DA D—H⋯A
O1—H1⋯N1 0.86 1.87 2.6456 (18) 149

The H atom of the hydr­oxyl group was found in a difference Fourier map. The other H atoms were placed in idealized positions with C—H = 0.95 Å. All the H atoms were refined as riding, with Uiso(H) = 1.2Ueq(C).

Data collection: WinAFC (Rigaku/MSC, 2004[Rigaku/MSC (2004). WinAFC and CrystalStructure. Version 3.7.0. Rigaku/MSC, 9009 New Trails Drive, The Woodlands, TX 77381-5209, USA.]); cell refinement: WinAFC; data reduction: CrystalStructure (Rigaku/MSC, 2004[Rigaku/MSC (2004). WinAFC and CrystalStructure. Version 3.7.0. Rigaku/MSC, 9009 New Trails Drive, The Woodlands, TX 77381-5209, USA.]); program(s) used to solve structure: SIR92 (Altomare et al., 1994[Altomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C., Polidori, G. & Camalli, M. (1994). J. Appl. Cryst. 27, 435.]); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003[Betteridge, P. W., Carruthers, J. R., Cooper, R. I., Prout, K. & Watkin, D. J. (2003). J. Appl. Cryst. 36, 1487.]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997[Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.]); software used to prepare material for publication: CrystalStructure.

Supporting information


Computing details top

Data collection: WinAFC (Rigaku/MSC, 2004); cell refinement: WinAFC; data reduction: CrystalStructure (Rigaku/MSC, 2004); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: CrystalStructure.

2,4-Dichloro-6-(piperidin-1-ylmethyl)phenol top
Crystal data top
C12H15Cl2NOF(000) = 544.00
Mr = 260.15Dx = 1.356 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71069 Å
Hall symbol: -P 2ybcCell parameters from 25 reflections
a = 9.571 (4) Åθ = 15.5–17.1°
b = 11.794 (4) ŵ = 0.49 mm1
c = 11.345 (5) ÅT = 298 K
β = 95.89 (3)°Prism, colorless
V = 1273.9 (9) Å30.50 × 0.20 × 0.20 mm
Z = 4
Data collection top
Rigaku AFC-7R
diffractometer
θmax = 27.5°
ω–2θ scansh = 1212
3619 measured reflectionsk = 150
2937 independent reflectionsl = 814
2773 reflections with F2 > 2σ(F2)3 standard reflections every 150 reflections
Rint = 0.026 intensity decay: 2.4%
Refinement top
Refinement on F2H-atom parameters constrained
R[F2 > 2σ(F2)] = 0.039 w = 1/[0.0034Fo2 + 1σ(Fo2)]/(4Fo2)
wR(F2) = 0.133(Δ/σ)max < 0.001
S = 1.01Δρmax = 0.29 e Å3
2776 reflectionsΔρmin = 0.52 e Å3
160 parameters
Special details top

Geometry. ENTER SPECIAL DETAILS OF THE MOLECULAR GEOMETRY

Refinement. Refinement using reflections with F2 > 2.0 σ(F2). The weighted R-factor (wR) and goodness of fit (S) are based on F2. R-factor (gt) are based on F. The threshold expression of F2 > 2.0 σ(F2) is used only for calculating R-factor (gt).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Cl10.00145 (5)0.00105 (4)0.34766 (4)0.06163 (16)
Cl20.15815 (5)0.25596 (4)0.00840 (5)0.06854 (18)
O10.13660 (12)0.18416 (10)0.23010 (10)0.0490 (3)
N10.32577 (12)0.25542 (11)0.09257 (12)0.0405 (3)
C10.13976 (13)0.08428 (12)0.17126 (12)0.0365 (3)
C20.08247 (14)0.01252 (13)0.21869 (14)0.0386 (3)
C30.08777 (14)0.11769 (13)0.16480 (13)0.0413 (4)
C40.14981 (16)0.12490 (13)0.06086 (14)0.0430 (4)
C50.20396 (16)0.02974 (14)0.00985 (13)0.0426 (4)
C60.19853 (14)0.07499 (13)0.06342 (12)0.0380 (3)
C70.24692 (17)0.18072 (14)0.00526 (12)0.0451 (4)
C80.46615 (17)0.20956 (14)0.12827 (17)0.0492 (4)
C90.5435 (2)0.28102 (19)0.22575 (18)0.0598 (5)
C100.5516 (2)0.40308 (18)0.1869 (2)0.0624 (5)
C110.40624 (18)0.44785 (16)0.1433 (2)0.0597 (5)
C120.33535 (18)0.37185 (14)0.04735 (17)0.0495 (4)
H10.20230.22520.20610.060*
H20.05020.18310.19890.049*
H30.24550.03720.06230.051*
H40.16730.22070.03020.054*
H50.30530.15990.05410.054*
H60.45720.13390.15520.058*
H70.51880.21000.06170.059*
H80.49290.27770.29340.071*
H90.63550.25190.24540.071*
H100.59080.44810.25140.075*
H110.60980.40750.12400.074*
H120.35050.44840.20800.072*
H130.41340.52270.11370.072*
H140.38960.37190.01820.060*
H150.24360.39910.02280.059*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0704 (3)0.0678 (3)0.0514 (3)0.0096 (2)0.0291 (2)0.0034 (2)
Cl20.0754 (3)0.0506 (3)0.0815 (4)0.0108 (2)0.0169 (3)0.0219 (2)
O10.0556 (6)0.0418 (6)0.0522 (6)0.0045 (5)0.0185 (5)0.0036 (5)
N10.0360 (6)0.0403 (7)0.0448 (7)0.0068 (5)0.0027 (5)0.0067 (5)
C10.0324 (6)0.0399 (8)0.0372 (7)0.0003 (5)0.0035 (5)0.0021 (6)
C20.0330 (7)0.0458 (8)0.0378 (7)0.0012 (5)0.0069 (5)0.0058 (6)
C30.0329 (7)0.0424 (8)0.0479 (8)0.0076 (6)0.0012 (6)0.0049 (6)
C40.0373 (7)0.0425 (8)0.0485 (9)0.0048 (6)0.0013 (6)0.0056 (7)
C50.0372 (7)0.0530 (9)0.0383 (8)0.0058 (7)0.0071 (6)0.0042 (7)
C60.0318 (6)0.0460 (8)0.0358 (7)0.0059 (5)0.0022 (5)0.0037 (6)
C70.0446 (8)0.0526 (9)0.0380 (8)0.0104 (7)0.0032 (6)0.0070 (7)
C80.0406 (8)0.0426 (9)0.0633 (11)0.0031 (7)0.0004 (7)0.0057 (8)
C90.0481 (9)0.0676 (12)0.0612 (11)0.0068 (8)0.0061 (8)0.0005 (9)
C100.0526 (10)0.0561 (11)0.0772 (13)0.0122 (8)0.0008 (9)0.0112 (9)
C110.0570 (10)0.0440 (10)0.0794 (13)0.0071 (8)0.0137 (9)0.0042 (9)
C120.0459 (8)0.0433 (9)0.0595 (10)0.0035 (7)0.0074 (7)0.0114 (8)
Geometric parameters (Å, º) top
Cl1—C21.7323 (17)C11—C121.516 (2)
Cl2—C41.7396 (17)O1—H10.860
O1—C11.3559 (19)C3—H20.950
N1—C71.474 (2)C5—H30.950
N1—C81.466 (2)C7—H40.950
N1—C121.472 (2)C7—H50.950
C1—C21.398 (2)C8—H60.950
C1—C61.402 (2)C8—H70.950
C2—C31.386 (2)C9—H80.950
C3—C41.376 (2)C9—H90.950
C4—C51.387 (2)C10—H100.950
C5—C61.380 (2)C10—H110.950
C6—C71.506 (2)C11—H120.950
C8—C91.521 (2)C11—H130.950
C9—C101.510 (3)C12—H140.950
C10—C111.523 (2)C12—H150.950
C2···C5i3.609 (2)Cl1···Cl1ii3.4596 (17)
C4···C6i3.533 (2)Cl1···Cl2iii3.5734 (17)
C5···C2i3.609 (2)Cl2···Cl1iv3.5734 (17)
C6···C4i3.533 (2)
C7—N1—C8110.88 (12)N1—C7—H5109.4
C7—N1—C12111.67 (12)C6—C7—H4109.1
C8—N1—C12110.63 (12)C6—C7—H5109.0
O1—C1—C2119.38 (13)H4—C7—H5109.5
O1—C1—C6121.91 (13)N1—C8—H6109.0
C2—C1—C6118.71 (14)N1—C8—H7108.9
Cl1—C2—C1118.49 (12)C9—C8—H6109.9
Cl1—C2—C3119.67 (12)C9—C8—H7108.5
C1—C2—C3121.84 (15)H6—C8—H7109.5
C2—C3—C4118.15 (15)C8—C9—H8108.3
Cl2—C4—C3119.06 (12)C8—C9—H9109.9
Cl2—C4—C5119.61 (13)C10—C9—H8108.7
C3—C4—C5121.33 (15)C10—C9—H9109.8
C4—C5—C6120.52 (15)H8—C9—H9109.5
C1—C6—C5119.39 (14)C9—C10—H10109.6
C1—C6—C7119.11 (14)C9—C10—H11108.9
C5—C6—C7121.41 (14)C11—C10—H10109.3
N1—C7—C6111.09 (12)C11—C10—H11108.9
N1—C8—C9111.12 (14)H10—C10—H11109.5
C8—C9—C10110.59 (16)C10—C11—H12108.6
C9—C10—C11110.66 (15)C10—C11—H13109.9
C10—C11—C12110.78 (15)C12—C11—H12108.3
N1—C12—C11109.91 (14)C12—C11—H13109.8
C1—O1—H1106.2H12—C11—H13109.5
C2—C3—H2121.00N1—C12—H14109.4
C4—C3—H2121.00N1—C12—H15109.2
C4—C5—H3119.00C11—C12—H14108.8
C6—C5—H3120.00C11—C12—H15110.0
N1—C7—H4108.7H14—C12—H15109.5
C7—N1—C8—C9175.31 (14)Cl1—C2—C3—C4178.40 (11)
C8—N1—C7—C673.99 (16)C1—C2—C3—C41.0 (2)
C7—N1—C12—C11175.25 (13)C2—C3—C4—Cl2179.87 (11)
C12—N1—C7—C6162.14 (13)C2—C3—C4—C50.9 (2)
C8—N1—C12—C1160.74 (18)Cl2—C4—C5—C6179.93 (11)
C12—N1—C8—C960.22 (19)C3—C4—C5—C60.9 (2)
O1—C1—C2—Cl13.24 (18)C4—C5—C6—C11.1 (2)
O1—C1—C2—C3177.40 (13)C4—C5—C6—C7175.45 (13)
O1—C1—C6—C5177.40 (13)C1—C6—C7—N144.20 (18)
O1—C1—C6—C76.0 (2)C5—C6—C7—N1139.28 (14)
C2—C1—C6—C52.9 (2)N1—C8—C9—C1056.2 (2)
C2—C1—C6—C7173.73 (12)C8—C9—C10—C1152.9 (2)
C6—C1—C2—Cl1176.51 (10)C9—C10—C11—C1254.2 (2)
C6—C1—C2—C32.8 (2)C10—C11—C12—N157.7 (2)
Symmetry codes: (i) x, y, z; (ii) x, y, z+1; (iii) x, y1/2, z+1/2; (iv) x, y1/2, z1/2.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1···N10.861.872.6456 (18)149
 

Acknowledgements

This study was supported financially in part by Grants-in-Aid for Scientific Research (No.16750061) from the Japan Society for the Promotion of Science.

References

First citationAltomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C., Polidori, G. & Camalli, M. (1994). J. Appl. Cryst. 27, 435.  CrossRef Web of Science IUCr Journals Google Scholar
First citationBetteridge, P. W., Carruthers, J. R., Cooper, R. I., Prout, K. & Watkin, D. J. (2003). J. Appl. Cryst. 36, 1487.  Web of Science CrossRef IUCr Journals Google Scholar
First citationDeng, X., Guo, Y.-M., Du, M. & Fang, Y.-Y. (2001). Acta Cryst. E57, o488–o489.  Web of Science CSD CrossRef IUCr Journals Google Scholar
First citationFarrugia, L. J. (1997). J. Appl. Cryst. 30, 565.  CrossRef IUCr Journals Google Scholar
First citationHirayama, N., Horita, Y., Oshima, S., Kubono, K., Kokusen, H. & Honjo, T. (2001). Talanta, 53, 857–862.  Web of Science CrossRef PubMed CAS Google Scholar
First citationHu, X. E., Kim, N. K., Ledoussal, B. & Colson, A.-O. (2002). Tetrahedron Lett. 43, 4289–4293.  Web of Science CrossRef CAS Google Scholar
First citationRigaku/MSC (2004). WinAFC and CrystalStructure. Version 3.7.0. Rigaku/MSC, 9009 New Trails Drive, The Woodlands, TX 77381-5209, USA.  Google Scholar
First citationWalker, S. M., Williams, J. T., Russell, A. G. & Snaith, J. S. (2005). Tetrahedron Lett. 46, 6611–6615.  Web of Science CSD CrossRef CAS Google Scholar
First citationYuan, D., Zhang, M., Pan, Z. & Ma, P. (2004). Acta Cryst. E60, o1321–o1322.  Web of Science CSD CrossRef IUCr Journals Google Scholar

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