4-(4-Chloro­phen­yl)piperidin-4-ol

Grzegorz Dutkiewicz; B P Siddaraju; H S Yathirajan; M S Siddegowda; Maciej Kubicki

doi:10.1107/S1600536810004216

. 2010 Feb 6;66(Pt 3):o562. doi: 10.1107/S1600536810004216

4-(4-Chlorophenyl)piperidin-4-ol

Grzegorz Dutkiewicz ^a, B P Siddaraju ^b, H S Yathirajan ^c, M S Siddegowda ^c, Maciej Kubicki ^a,^*

PMCID: PMC2983646 PMID: 21580330

Abstract

In the title compound, C₁₁H₁₄ClNO, the piperidine ring adopts a chair conformation: the hydroxyl substituent and the N-bound H atom occupy the axial positions, while the benzene ring occupies the equatorial position. In the crystal, the molecules are linked into a centrosymmetric tetramer through strong O—H⋯N and weak N—H⋯O hydrogen bonds; the N and O atoms act as both donor and acceptor for these interactions. The tetramers are further joined by hydrogen bonds into a layer parallel to (100).

Related literature

For related structures, see: De Camp & Ahmed (1972a ▶,b ▶); Friederich et al. (1993 ▶); Kimura & Okabayashi (1986 ▶). For details of the asymmetry parameters for chair conformations, see: Duax & Norton (1975 ▶). For a description of the Cambridge Structural Database, see: Allen (2002 ▶).

Experimental

Crystal data

C₁₁H₁₄ClNO
M _r = 211.68
Monoclinic,
a = 11.3706 (10) Å
b = 9.5204 (8) Å
c = 10.6164 (9) Å
β = 108.458 (8)°
V = 1090.13 (16) Å³
Z = 4
Cu Kα radiation
μ = 2.83 mm⁻¹
T = 295 K
0.3 × 0.2 × 0.15 mm

Data collection

Oxford Diffraction SuperNova, single source at offset, Atlas diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009 ▶) T _min = 0.401, T _max = 0.654
4068 measured reflections
2190 independent reflections
2014 reflections with I > 2σ(I)
R _int = 0.011

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.111
S = 1.07
2190 reflections
183 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.38 e Å⁻³

Data collection: CrysAlis PRO (Oxford Diffraction, 2009 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SIR92 (Altomare et al., 1993 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: Stereochemical Workstation Operation Manual (Siemens, 1989 ▶) and Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810004216/is2520sup1.cif

e-66-0o562-sup1.cif^{(16.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810004216/is2520Isup2.hkl

e-66-0o562-Isup2.hkl^{(105.5KB, hkl)}

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⋯O4ⁱ	0.89 (2)	2.41 (2)	3.2036 (16)	147.2 (17)
O4—H4A⋯N1ⁱⁱ	0.84 (2)	1.97 (2)	2.8089 (17)	174 (2)

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

Acknowledgments

BPS thanks R. L. FineChem, Bangalore, India, for the gift of a sample of the title compound.

supplementary crystallographic information

Comment

The title compound, (1, Scheme 1), 4-(4-chlorophenyl)piperidin-4-ol is used as an intermediate for the synthesis of pharmaceuticals such as haloperidol (neuroleptic drug used to treat psychotic illnesses, extreme agitation, or Tourette's syndrome) and loperamide which is effective against diarrhea resulting from gastroenteritis or inflammatory bowel disease.

The piperidine ring adopts an almost ideal chair conformation (Fig. 1); the asymmetry parameters (Duax & Norton, 1975) are all smaller than 2.5°. The hydroxy group and N—H hydrogen atom occupy the axial positions [torsion angles: C2—C3—C4—O4 -64.46 (15)°, C6—C5—C4—O4 60.81 (15)°, C5—C6—N1—H1 65.0 (13)°, and C3—C2—N1—H1 -64.8 (14)°]. Such a mutual conformation of hydroxyl and phenyl groups is very typical, in the Cambridge Database (Allen, 2002; ver. 5.30 of Nov. 2008, last update Sep. 2009) there are 65 crystal structures of six-membered saturated rings with both OH and aromatic substituent in one position, only in three of them the hydroxyl group adopts the equatorial position [two polymorphs of (±)-β-1,2,5-trimethyl-4-phenylpiperidin-4-ol (De Camp & Ahmed, 1972a,b), cis-1,4-bis(4-bromophenyl)-1,4-dimethoxycyclohexane (Friederich et al., 1993), and cis-1-phenyl-3-piperidinocyclohexan-1-ol hydrochloride (Kimura & Okabayashi, 1986)].

The relatively strong and directional O—H···N hydrogen bonds join the molecules of 1, related by two-fold screw axis, into the chains along [010] directions. These chains are interconnected by far weaker N—H···O hydrogen bonds. These two kinds of contacts form centrosymmetric tetramers of the molecules (Fig. 2). In the crystal structures there are the hydrogen-bonded layers of molecules, created by interconnecting chains, in the bc plane (Fig. 3a). There are no directional interactions between neighbouring layers (Fig. 3b).

Experimental

The title compound was obtained as a gift sample from R. L. Fine Chem, Bangalore, India. X-ray quality crystals were obtained by a slow evaporation from an ethyl acetate solution (m.p. 410–413 K).