4-Chloro-2-((1R)-1-{[(R)-(2-chloro­phen­yl)(cyclo­pent­yl)meth­yl]amino}eth­yl)phenol

Guang-You Zhang; Ting Yang; Bao-Wang Xu; Di-Juan Chen; Wan-Hui Wang

doi:10.1107/S1600536808034624

. 2008 Oct 25;64(Pt 11):o2211–o2212. doi: 10.1107/S1600536808034624

4-Chloro-2-((1R)-1-{[(R)-(2-chlorophenyl)(cyclopentyl)methyl]amino}ethyl)phenol

Guang-You Zhang ^a, Ting Yang ^a,^*, Bao-Wang Xu ^b, Di-Juan Chen ^a, Wan-Hui Wang ^c

PMCID: PMC2959664 PMID: 21581069

Abstract

The title compound, C₂₀H₂₃Cl₂NO, was prepared by condensation of (R)-1-(2-chlorophenyl)-1-cyclopentylmethanamine with 1-(5-chloro-2-hydroxyphenyl)ethanone, resulting in the formation of a new chiral center. The structural analysis confirms the absolute configuration of the title compound and the formation of the (R,R) diastereoisomer. There is an intramolecular O—H⋯N hydrogen bond which stabilizes the conformation of the molecule. The molecules are linked to each other through weak C—H⋯π interactions.

Related literature

For general background, see: Ager et al. (1996 ▶); Berrisford et al. (1995 ▶); Cimarelli & Palmieri (1998 ▶); Cimarelli et al. (2001 ▶, 2002 ▶); Hayase et al. (1997 ▶); Nakano et al. (1997 ▶); Palmieri (1999 ▶, 2000 ▶); Soai & Niwa (1992 ▶); Watanabe et al. (1991 ▶); Xu & Pu (2004 ▶); Yang et al. (2005 ▶).

Experimental

Crystal data

C₂₀H₂₃Cl₂NO
M _r = 364.29
Orthorhombic,
a = 11.286 (2) Å
b = 11.539 (2) Å
c = 14.740 (3) Å
V = 1919.5 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.34 mm⁻¹
T = 298 (2) K
0.42 × 0.29 × 0.18 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1997 ▶) T _min = 0.869, T _max = 0.941
10145 measured reflections
3573 independent reflections
2761 reflections with I > 2σ(I)
R _int = 0.032

Refinement

R[F ² > 2σ(F ²)] = 0.048
wR(F ²) = 0.113
S = 1.02
3573 reflections
219 parameters
H-atom parameters constrained
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.22 e Å⁻³
Absolute structure: Flack (1983 ▶), 1629 Friedel pairs
Flack parameter: 0.03 (8)

Data collection: SMART (Bruker, 1997 ▶); cell refinement: SAINT (Bruker, 1997 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEPIII (Burnett & Johnson, 1996 ▶) and ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808034624/dn2393sup1.cif

e-64-o2211-sup1.cif^{(20.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808034624/dn2393Isup2.hkl

e-64-o2211-Isup2.hkl^{(175.2KB, 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
O1—H1A⋯N1	0.82	1.92	2.639 (3)	146
C3—H3⋯Cg1ⁱ	0.93	2.76	3.661 (3)	164

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Symmetry code: (i) Inline graphic . Cg is the centroid of the C15–C20 benzene ring

Acknowledgments

The authors are grateful to the Natural Science Foundation of Shandong Province China (grant No. G0231) and the Foundation of the Education Ministry of China for Returned Students (grant No. G0220) for financial support. The X-ray data were collected at Shandong Normal University, China.

supplementary crystallographic information

Comment

The synthesis of enantiopure amine alcohols with a variety of functionalities is an important subject of research because this class of compounds has found widespread application in biological systems showing pharmacological activity. These compounds are used as resolving agents, chiral bases and auxiliaries in asymmetric synthesis (Cimarelli et al.,2002), and most have been derived from new readily available natural products (Ager et al.,1996). Chiral aminophenols, which are similar to aminoalcohols, are important building blocks in organic synthesis, and have attracted increasing attention in recent years owing to their effects in asymmetric synthesis and asymmetric induction (Cimarelli et al.,2001; Palmieri, 1999, 2000; Xu & Pu, 2004; Berrisford et al., 1995; Cimarelli & Palmieri, 1998; Hayase et al., 1997; Nakano et al.,1997; Soai et al., 1992; Watanabe et al., 1991).

As part of our continuing studies of chiral aminophenols, we have established the molecular structure of the title compound which was intially synthesized to test its asymmetric catalytic activity. The compound has been prepared by conventional condensation of (R)-1-(2-chlorophenyl)-1-cyclopentylmethanamine with 1-(5-chloro-2-hydroxyphenyl)ethanone, resulting in the formation of a new chiral center as shown in Fig. 1.

The structural analyses confirms the absolute configuration of the title compound and the formation of the (R,R) diastereoisomer. There is an intramolecular O-H···N hydrogen bond which stabilizes the conformation of the molecule. The molecules are linked to each other through weak C-H···π interaction involving the C15-C20 benzene ring (Table 1).

Experimental

The title compound were prepared according to the procedure of Yang et al.(2005). (R)-1-(2-chlorophenyl)-1-cyclopentylmethanamine (0.9 mmol) and 1-(5-chloro-2-hydroxyphenyl)ethanone (0.9 mmol) were dissolved in methanol (10 ml) and reacted at room temperature for 48 h. After removal of the solvent, NaBH₄ (4.5 mmol) was added to the solution in THF/ethanol (1:1 v/v, 20 ml) and stirred at 273 K until the solution became colourless. The solvent was then removed under reduced pressure. Water (10 ml)was added to the residue and 1 N HCl was added dropwise until hydrogen production ceased. The mixture was neutralized with aqueous Na₂CO₃, then extracted with CHCl_3,and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. Further purification was carried out by thin-layer silica-gel chromatography (chloroform) to give a colourless solid (yield 83.5%). Crystals of (I) were grown from a n-hexane.