(1S,2R,4S)-1-[(Benzyl­amino)­meth­yl]-4-(prop-1-en-2-yl)cyclo­hexane-1,2-diol

Rachid Outouch; Brahim Boualy; Mustapha Ait Ali; Larbi El Firdoussi; Corrado Rizzoli

doi:10.1107/S1600536810052323

. 2010 Dec 18;67(Pt 1):o195–o196. doi: 10.1107/S1600536810052323

(1S,2R,4S)-1-[(Benzylamino)methyl]-4-(prop-1-en-2-yl)cyclohexane-1,2-diol

Rachid Outouch ^a, Brahim Boualy ^a, Mustapha Ait Ali ^a, Larbi El Firdoussi ^a, Corrado Rizzoli ^b,^*

PMCID: PMC3050382 PMID: 21522697

Abstract

The title compound, C₁₇H₂₅NO₂, was synthesized by epoxidation of the double bond of (S)-perillyl alcohol [(S)-4-isopropenyl-1-cyclohexenylmethanol], followed by the oxirane ring-opening by benzylamine using [Ca(CF₃CO₂)₂] as catalyst under solvent-free condition at 313 K. The molecular conformation is stabilized by an intramolecular O—H⋯N hydrogen bond. In the crystal, molecules are linked by intermolecular N—H⋯O hydrogen bonds, forming chains parallel to the a axis, which are further connected by O—H⋯O hydrogen bonds into sheets parallel to (010). The absolute configuration of the molecule is known from the synthetic procedure.

Related literature

For the biological activity and applications of aminodiols, see: Alexander & Liotta (1996 ▶); Allepuz et al. (2010 ▶); Beaulieu et al. (1999 ▶); Braga et al. (2003 ▶); Chen et al. (1996 ▶); Cherng et al. (1995 ▶, 1999 ▶); Gondela & Walczak (2010 ▶); Kempf et al. (1992 ▶); Panev et al. (2001 ▶); Pastó et al. (1996 ▶); Wang et al. (1995 ▶). For the synthesis of amidiol derivatives, see: Ager et al. (1996 ▶); Bergmeier (2000 ▶); Canas et al. (1991 ▶); Carree et al. (2004 ▶); Dias et al. (2008 ▶); Fan & Hou (2003 ▶); Kamal et al. (2005 ▶); Kwon & Ko (2003 ▶); Lee & Kang (2004 ▶); Szakonyi et al. (2008 ▶); Zhao et al. (2004 ▶). For the use of [Ca(CF₃CO₂)₂] as catalyst, see: Harrad et al. (2010 ▶). For the synthesis of (S)-1,2-epoxyperillyl alcohol, see: Bach et al. (1979 ▶). For the graph-set analysis of hydrogen bonding, see: Bernstein et al. (1995 ▶). For details of ring-puckering analysis, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₁₇H₂₅NO₂
M _r = 275.38
Monoclinic,
a = 5.8281 (4) Å
b = 24.5421 (16) Å
c = 5.8776 (4) Å
β = 105.908 (4)°
V = 808.50 (10) Å³
Z = 2
Cu Kα radiation
μ = 0.58 mm⁻¹
T = 294 K
0.20 × 0.17 × 0.15 mm

Data collection

Siemens AED diffractometer
3041 measured reflections
1567 independent reflections
1477 reflections with I > 2σ(I)
R _int = 0.010
3 standard reflections every 100 reflections intensity decay: 0.02%

Refinement

R[F ² > 2σ(F ²)] = 0.031
wR(F ²) = 0.092
S = 1.08
1567 reflections
195 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.16 e Å⁻³
Δρ_min = −0.09 e Å⁻³

Data collection: AED (Belletti et al., 1993 ▶); cell refinement: AED; data reduction: AED; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶) and SCHAKAL97 (Keller, 1997 ▶); software used to prepare material for publication: SHELXL97 and PARST95 (Nardelli, 1995 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810052323/gk2332sup1.cif

e-67-0o195-sup1.cif^{(17.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810052323/gk2332Isup2.hkl

e-67-0o195-Isup2.hkl^{(77.2KB, 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
O2—H2O⋯N1	0.90 (3)	1.88 (3)	2.676 (2)	147 (3)
O1—H1O⋯O2ⁱ	0.83 (3)	1.89 (3)	2.721 (2)	171 (3)
N1—H1N⋯O1ⁱⁱ	0.92 (2)	2.15 (2)	3.037 (2)	164 (2)

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

Acknowledgments

Financial support from the Universitá degli Studi di Parma is gratefully acknowledged.

supplementary crystallographic information

Comment

Aminodiols play important roles in drug therapy and drug research. For example, 5-(ω-hydroxyalkylamino) derivatives of mucochloric acids (2,3-dichloro-4-oxo-2-butenoic acid) have antibacterial and antiprotozoal activities (Gondela & Walczak, 2010). Other aminodiols have been found to act as HIV protease inhibitors (Kempf et al., 1992; Wang et al., 1995; Chen et al., 1996), or to exert renin inhibitor activity (Alexander & Liotta, 1996; Beaulieu et al., 1999). Furthermore, aminodiols may serve as useful starting materials for the synthesis of biologically active compounds, e. g. 3-amino-1,2-butanediol derivatives, which are key intermediates in the synthesis of the anticancer agent ES-285 (Allepuz et al., 2010). Chiral aminodiols and their derivatives also find excellent applications as catalysts for enantioselective transformations (Panev et al., 2001; Cherng et al., 1995, 1999; Pastó et al., 1996; Braga et al., 2003).

Among many different approaches developed for the synthesis of aminodiol derivatives (Canas et al., 1991; Panev et al., 2001; Kwon & Ko, 2003; Dias et al., 2008; Szakonyi et al., 2008), aminolysis of 1,2-epoxides represents one of the most valuable pathway to produce commercially important aminoalcohols and aminodiols from olefins (Ager et al., 1996; Bergmeier, 2000; Lee & Kang, 2004; Zhao et al., 2004; Fan & Hou, 2003; Kamal et al., 2005; Carree et al., 2004). As a contribution to this widespread area, we describe here the synthesis and crystal structure of the title new aminodiol derivative of perillyl alcohol. The synthetic methodology involves an epoxidation of the double bond, followed by the oxirane ring-opening by using benzylamine and Ca(CF₃CO₂)₂ as catalyst (Harrad et al., 2010) under solvent-free condition at 40°C.

The molecular structure of the title compound is shown in Fig. 1. The cyclohexane ring is in a chair conformation, with puckering parameters Q, θ and φ of 0.560 (2) Å, 2.6 (2)° and -167 (4)°, respectively (Cremer & Pople, 1975). The hydroxy groups at atoms C1 and C2 are both in axial positions. The molecular conformation is stabilized by an intramolecular O—H···N hydrogen bond (Table 1), generating a ring of S(6) graph set motif (Bernstein et al., 1995). In the crystal structure (Fig. 2), molecules are linked into chains parallel to the a axis by intermolecular N—H···O hydrogen bonds. The chains are further connected via O—H···O hydrogen bonding interactions to form sheets parallel to (010).

Experimental

(S)-1,2-Epoxyperillyl alcohol was prepared from commercially available (S)-perillyl alcohol [(S)-4-isopropenyl-1-cyclohexenylmethanol, Fluka] using the procedure described in the literature (Bach et al., 1979). A mixture of benzylamine (5.1 mmol) and (S)-1,2-epoxyperillyl alcohol (5 mmol) was added to Ca(CF₃CO₂)₂ (0.25 mmol) under solvent-free conditions. The mixture was stirred at 40 °C for 72 h, then it was extracted with ethyl acetate (3 × 10 ml), dried over Na₂SO₄ and the solvent was removed under reduced pressure. Column chromatography (column 60 x 2.5 cm, hexane) of the residue on silica gel gave the title aminodiol in 52% yield (m. p. 429-430 K). Colourless crystals suitable for X-ray analysis were obtained on slow evaporation of the solvent.