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

Kubono, K.; Oshima, S.; Hirayama, N.; Yokoi, K.

doi:10.1107/S1600536805032290

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 61| Part 11| November 2005| Pages o3706-o3708

https://doi.org/10.1107/S1600536805032290

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

Koji Kubono,^a ^* Syunichi Oshima,^b Naoki Hirayama ^c and Kunihiko Yokoi ^a

^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 π–π 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 ; Walker et al., 2005 ). 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 ), and in this work, describe the crystal structure of 2,4-dichloro-6-(piperidin-1-ylmethyl)phenol, (I), which would be expected to act as an effective chelating reagent.

Compound (I) 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 ; Yuan et al., 2004 ). 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).

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 π–π interactions and Cl⋯Cl contacts between dichlorobenzene groups.

Figure 1
A view of the molecule of (I)

, 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
The packing of the molecules of (I)

, viewed down the a axis, with Cl⋯Cl contacts shown as dashed lines.

Experimental

Compound (I) 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
M_r = 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
D_x = 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)
R_int = 0.026
θ_max = 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/[0.0034F_o² + 1σ(F_o²)]/(4F_o²)
(Δ/σ)_max < 0.001
Δρ_max = 0.29 e Å⁻³
Δρ_min = −0.52 e Å⁻³

Table 1
Selected geometric parameters (Å, °)

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, °)

D—H⋯A	D—H	H⋯A	D⋯A	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 U_iso(H) = 1.2U_eq(C).

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.

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536805032290/hg6252sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536805032290/hg6252Isup2.hkl

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

C₁₂H₁₅Cl₂NO	F(000) = 544.00
M_r = 260.15	D_x = 1.356 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71069 Å
Hall symbol: -P 2ybc	Cell parameters from 25 reflections
a = 9.571 (4) Å	θ = 15.5–17.1°
b = 11.794 (4) Å	µ = 0.49 mm⁻¹
c = 11.345 (5) Å	T = 298 K
β = 95.89 (3)°	Prism, colorless
V = 1273.9 (9) Å³	0.50 × 0.20 × 0.20 mm
Z = 4

Data collection top

Rigaku AFC-7R diffractometer	θ_max = 27.5°
ω–2θ scans	h = −12→12
3619 measured reflections	k = −15→0
2937 independent reflections	l = −8→14
2773 reflections with F² > 2σ(F²)	3 standard reflections every 150 reflections
R_int = 0.026	intensity decay: 2.4%

Refinement top

Refinement on F²	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.039	w = 1/[0.0034F_o² + 1σ(F_o²)]/(4F_o²)
wR(F²) = 0.133	(Δ/σ)_max < 0.001
S = 1.01	Δρ_max = 0.29 e Å⁻³
2776 reflections	Δρ_min = −0.52 e Å⁻³
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

	x	y	z	U_iso*/U_eq
Cl1	0.00145 (5)	0.00105 (4)	0.34766 (4)	0.06163 (16)
Cl2	0.15815 (5)	−0.25596 (4)	−0.00840 (5)	0.06854 (18)
O1	0.13660 (12)	0.18416 (10)	0.23010 (10)	0.0490 (3)
N1	0.32577 (12)	0.25542 (11)	0.09257 (12)	0.0405 (3)
C1	0.13976 (13)	0.08428 (12)	0.17126 (12)	0.0365 (3)
C2	0.08247 (14)	−0.01252 (13)	0.21869 (14)	0.0386 (3)
C3	0.08777 (14)	−0.11769 (13)	0.16480 (13)	0.0413 (4)
C4	0.14981 (16)	−0.12490 (13)	0.06086 (14)	0.0430 (4)
C5	0.20396 (16)	−0.02974 (14)	0.00985 (13)	0.0426 (4)
C6	0.19853 (14)	0.07499 (13)	0.06342 (12)	0.0380 (3)
C7	0.24692 (17)	0.18072 (14)	0.00526 (12)	0.0451 (4)
C8	0.46615 (17)	0.20956 (14)	0.12827 (17)	0.0492 (4)
C9	0.5435 (2)	0.28102 (19)	0.22575 (18)	0.0598 (5)
C10	0.5516 (2)	0.40308 (18)	0.1869 (2)	0.0624 (5)
C11	0.40624 (18)	0.44785 (16)	0.1433 (2)	0.0597 (5)
C12	0.33535 (18)	0.37185 (14)	0.04735 (17)	0.0495 (4)
H1	0.2023	0.2252	0.2061	0.060*
H2	0.0502	−0.1831	0.1989	0.049*
H3	0.2455	−0.0372	−0.0623	0.051*
H4	0.1673	0.2207	−0.0302	0.054*
H5	0.3053	0.1599	−0.0541	0.054*
H6	0.4572	0.1339	0.1552	0.058*
H7	0.5188	0.2100	0.0617	0.059*
H8	0.4929	0.2777	0.2934	0.071*
H9	0.6355	0.2519	0.2454	0.071*
H10	0.5908	0.4481	0.2514	0.075*
H11	0.6098	0.4075	0.1240	0.074*
H12	0.3505	0.4484	0.2080	0.072*
H13	0.4134	0.5227	0.1137	0.072*
H14	0.3896	0.3719	−0.0182	0.060*
H15	0.2436	0.3991	0.0228	0.059*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0704 (3)	0.0678 (3)	0.0514 (3)	−0.0096 (2)	0.0291 (2)	0.0034 (2)
Cl2	0.0754 (3)	0.0506 (3)	0.0815 (4)	−0.0108 (2)	0.0169 (3)	−0.0219 (2)
O1	0.0556 (6)	0.0418 (6)	0.0522 (6)	−0.0045 (5)	0.0185 (5)	−0.0036 (5)
N1	0.0360 (6)	0.0403 (7)	0.0448 (7)	−0.0068 (5)	0.0027 (5)	0.0067 (5)
C1	0.0324 (6)	0.0399 (8)	0.0372 (7)	−0.0003 (5)	0.0035 (5)	0.0021 (6)
C2	0.0330 (7)	0.0458 (8)	0.0378 (7)	−0.0012 (5)	0.0069 (5)	0.0058 (6)
C3	0.0329 (7)	0.0424 (8)	0.0479 (8)	−0.0076 (6)	0.0012 (6)	0.0049 (6)
C4	0.0373 (7)	0.0425 (8)	0.0485 (9)	−0.0048 (6)	0.0013 (6)	−0.0056 (7)
C5	0.0372 (7)	0.0530 (9)	0.0383 (8)	−0.0058 (7)	0.0071 (6)	−0.0042 (7)
C6	0.0318 (6)	0.0460 (8)	0.0358 (7)	−0.0059 (5)	0.0022 (5)	0.0037 (6)
C7	0.0446 (8)	0.0526 (9)	0.0380 (8)	−0.0104 (7)	0.0032 (6)	0.0070 (7)
C8	0.0406 (8)	0.0426 (9)	0.0633 (11)	−0.0031 (7)	0.0004 (7)	0.0057 (8)
C9	0.0481 (9)	0.0676 (12)	0.0612 (11)	−0.0068 (8)	−0.0061 (8)	−0.0005 (9)
C10	0.0526 (10)	0.0561 (11)	0.0772 (13)	−0.0122 (8)	0.0008 (9)	−0.0112 (9)
C11	0.0570 (10)	0.0440 (10)	0.0794 (13)	−0.0071 (8)	0.0137 (9)	−0.0042 (9)
C12	0.0459 (8)	0.0433 (9)	0.0595 (10)	−0.0035 (7)	0.0074 (7)	0.0114 (8)

Geometric parameters (Å, º) top

Cl1—C2	1.7323 (17)	C11—C12	1.516 (2)
Cl2—C4	1.7396 (17)	O1—H1	0.860
O1—C1	1.3559 (19)	C3—H2	0.950
N1—C7	1.474 (2)	C5—H3	0.950
N1—C8	1.466 (2)	C7—H4	0.950
N1—C12	1.472 (2)	C7—H5	0.950
C1—C2	1.398 (2)	C8—H6	0.950
C1—C6	1.402 (2)	C8—H7	0.950
C2—C3	1.386 (2)	C9—H8	0.950
C3—C4	1.376 (2)	C9—H9	0.950
C4—C5	1.387 (2)	C10—H10	0.950
C5—C6	1.380 (2)	C10—H11	0.950
C6—C7	1.506 (2)	C11—H12	0.950
C8—C9	1.521 (2)	C11—H13	0.950
C9—C10	1.510 (3)	C12—H14	0.950
C10—C11	1.523 (2)	C12—H15	0.950

C2···C5ⁱ	3.609 (2)	Cl1···Cl1ⁱⁱ	3.4596 (17)
C4···C6ⁱ	3.533 (2)	Cl1···Cl2ⁱⁱⁱ	3.5734 (17)
C5···C2ⁱ	3.609 (2)	Cl2···Cl1^iv	3.5734 (17)
C6···C4ⁱ	3.533 (2)

C7—N1—C8	110.88 (12)	N1—C7—H5	109.4
C7—N1—C12	111.67 (12)	C6—C7—H4	109.1
C8—N1—C12	110.63 (12)	C6—C7—H5	109.0
O1—C1—C2	119.38 (13)	H4—C7—H5	109.5
O1—C1—C6	121.91 (13)	N1—C8—H6	109.0
C2—C1—C6	118.71 (14)	N1—C8—H7	108.9
Cl1—C2—C1	118.49 (12)	C9—C8—H6	109.9
Cl1—C2—C3	119.67 (12)	C9—C8—H7	108.5
C1—C2—C3	121.84 (15)	H6—C8—H7	109.5
C2—C3—C4	118.15 (15)	C8—C9—H8	108.3
Cl2—C4—C3	119.06 (12)	C8—C9—H9	109.9
Cl2—C4—C5	119.61 (13)	C10—C9—H8	108.7
C3—C4—C5	121.33 (15)	C10—C9—H9	109.8
C4—C5—C6	120.52 (15)	H8—C9—H9	109.5
C1—C6—C5	119.39 (14)	C9—C10—H10	109.6
C1—C6—C7	119.11 (14)	C9—C10—H11	108.9
C5—C6—C7	121.41 (14)	C11—C10—H10	109.3
N1—C7—C6	111.09 (12)	C11—C10—H11	108.9
N1—C8—C9	111.12 (14)	H10—C10—H11	109.5
C8—C9—C10	110.59 (16)	C10—C11—H12	108.6
C9—C10—C11	110.66 (15)	C10—C11—H13	109.9
C10—C11—C12	110.78 (15)	C12—C11—H12	108.3
N1—C12—C11	109.91 (14)	C12—C11—H13	109.8
C1—O1—H1	106.2	H12—C11—H13	109.5
C2—C3—H2	121.00	N1—C12—H14	109.4
C4—C3—H2	121.00	N1—C12—H15	109.2
C4—C5—H3	119.00	C11—C12—H14	108.8
C6—C5—H3	120.00	C11—C12—H15	110.0
N1—C7—H4	108.7	H14—C12—H15	109.5

C7—N1—C8—C9	−175.31 (14)	Cl1—C2—C3—C4	178.40 (11)
C8—N1—C7—C6	73.99 (16)	C1—C2—C3—C4	−1.0 (2)
C7—N1—C12—C11	175.25 (13)	C2—C3—C4—Cl2	179.87 (11)
C12—N1—C7—C6	−162.14 (13)	C2—C3—C4—C5	−0.9 (2)
C8—N1—C12—C11	−60.74 (18)	Cl2—C4—C5—C6	−179.93 (11)
C12—N1—C8—C9	60.22 (19)	C3—C4—C5—C6	0.9 (2)
O1—C1—C2—Cl1	3.24 (18)	C4—C5—C6—C1	1.1 (2)
O1—C1—C2—C3	−177.40 (13)	C4—C5—C6—C7	−175.45 (13)
O1—C1—C6—C5	177.40 (13)	C1—C6—C7—N1	44.20 (18)
O1—C1—C6—C7	−6.0 (2)	C5—C6—C7—N1	−139.28 (14)
C2—C1—C6—C5	−2.9 (2)	N1—C8—C9—C10	−56.2 (2)
C2—C1—C6—C7	173.73 (12)	C8—C9—C10—C11	52.9 (2)
C6—C1—C2—Cl1	−176.51 (10)	C9—C10—C11—C12	−54.2 (2)
C6—C1—C2—C3	2.8 (2)	C10—C11—C12—N1	57.7 (2)

Symmetry codes: (i) −x, −y, −z; (ii) −x, −y, −z+1; (iii) x, −y−1/2, z+1/2; (iv) x, −y−1/2, z−1/2.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···N1	0.86	1.87	2.6456 (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

Altomare, 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
Betteridge, 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
Deng, X., Guo, Y.-M., Du, M. & Fang, Y.-Y. (2001). Acta Cryst. E57, o488–o489. Web of Science CSD CrossRef IUCr Journals Google Scholar
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. CrossRef IUCr Journals Google Scholar
Hirayama, N., Horita, Y., Oshima, S., Kubono, K., Kokusen, H. & Honjo, T. (2001). Talanta, 53, 857–862. Web of Science CrossRef PubMed CAS Google Scholar
Hu, X. E., Kim, N. K., Ledoussal, B. & Colson, A.-O. (2002). Tetrahedron Lett. 43, 4289–4293. Web of Science CrossRef CAS Google Scholar
Rigaku/MSC (2004). WinAFC and CrystalStructure. Version 3.7.0. Rigaku/MSC, 9009 New Trails Drive, The Woodlands, TX 77381-5209, USA. Google Scholar
Walker, 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
Yuan, D., Zhang, M., Pan, Z. & Ma, P. (2004). Acta Cryst. E60, o1321–o1322. Web of Science CSD CrossRef IUCr Journals Google Scholar

© International Union of Crystallography. Prior permission is not required to reproduce short quotations, tables and figures from this article, provided the original authors and source are cited. For more information, click here.