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

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

doi:10.1107/S1600536808042025

. 2008 Dec 13;65(Pt 1):o123. doi: 10.1107/S1600536808042025

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

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

PMCID: PMC2968043 PMID: 21581584

Abstract

In the title compound, C₂₁H₂₅Cl₂NO, the dihedral angle between the two benzene rings is 33.18 (11)°. The five-membered ring adopts an envelope conformation. There is an intramolecular O—H⋯N hydrogen bond. In the crystal, molecules are linked by weak N—H⋯Cl hydrogen bonds, forming a helical chain along the c axis.

Related literature

For related literature on aminophenols, see: Cimarelli et al. (2002 ▶); Joshi & Malhotra (2003 ▶); Li et al. (2004 ▶); Puigjaner et al. (1999 ▶); Watts et al. (2005 ▶). For the synthesis, see: Yang et al. (2005 ▶).

Experimental

Crystal data

C₂₁H₂₅Cl₂NO
M _r = 378.32
Orthorhombic,
a = 10.9802 (17) Å
b = 11.5607 (18) Å
c = 15.536 (2) Å
V = 1972.1 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.34 mm⁻¹
T = 298 (2) K
0.49 × 0.45 × 0.38 mm

Data collection

Bruker SMART APEX CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.852, T _max = 0.882
10332 measured reflections
3647 independent reflections
3266 reflections with I > 2σ(I)
R _int = 0.025

Refinement

R[F ² > 2σ(F ²)] = 0.035
wR(F ²) = 0.093
S = 1.03
3647 reflections
231 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.20 e Å⁻³
Absolute structure: Flack (1983 ▶), 1556 Friedel pairs
Flack parameter: 0.06 (6)

Data collection: SMART (Bruker, 1999 ▶); cell refinement: SAINT (Bruker, 1999 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808042025/is2364sup1.cif

e-65-0o123-sup1.cif^{(21.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808042025/is2364Isup2.hkl

e-65-0o123-Isup2.hkl^{(178.9KB, 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⋯Cl2ⁱ	0.848 (19)	2.913 (13)	3.7023 (18)	156 (2)
O1—H1A⋯N1	0.82	1.93	2.642 (2)	144

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Symmetry code: (i) Inline graphic .

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 aminophenols that have different functionalities is an important subject of research because compounds of this class are widespread in natural products, show pharmacological activity and have recently found application in asymmetric synthesis as chiral bases, auxiliaries and ligands (Cimarelli et al., 2002). Chiral aminophenols which are similar to amino alcohols have attracted wide attention for the reason that they can be used in catalytic asymmetric reactions (Puigjaner et al., 1999; Li et al., 2004; Watts et al., 2005), which is one of the most active areas of research in organic chemistry (Joshi & Malhotra, 2003). The synthesis of new aminoalkylphenols is therefore of interest because of potential as asymmetric catalysts.

As part of our continuing studies of chiral aminophenols, we now report the crystal structure of the title compound, (I), which was intially prepared to test its asymmetric catalytic activity. These compounds were prepared by conventional condensation of (R)-1-(2-chlorophenyl)-1-cyclopentylmethanamine with 1-(5-chloro-2-hydroxyphenyl)ethanone, followed by reduction using sodium borohydride in a tetrahydrofuran-ethanol (1:1 v/v) mixture. An X-ray study of the title compound, (I), was carried out and the results are presented here. The molecular structure of (I) is shown in Fig. 1.

The molecule has two chiral centres (C7/C10), which have configuration R, R, as shown in Fig. 1. In the molecules of (I), the five-membered rings adopts an envelope conformation. The dihedral angle between the benzene rings is 33.18 (11)°. There is an intramolecular O1—H1A···N1 hydrogen bond (Table 1). Phenol atom O1 acts as a hydrogen bond donor to atom N1, with O1···N1 = 2.647 (2) Å, which indicates a comparatively strong intramolecular hydrogen bond (Table 1); this distance is significantly shorter than the sum (3.07 Å) of the van der Waals radii for N and O atoms. The molecules are linked via N1—H1···Cl2 hydrogen bonds. An interesting feature of the structure is that the N1—H1···Cl2 hydrogen-bond gives rise to a spiral chain of molecules along the c direction. There are no π-π stacking interactions are present in the structure of (I).

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)propan-1-one (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 CHCl₃, 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 80.5%). Crystals of (I) were grown from a n-hexane solution.