1,4a-Dimethyl-6-methyl­ene-5-(5,5,6,6-tetra­cyano-2-methyl­cyclo­hex-2-enylmeth­yl)deca­hydro­naphthalene-1-carboxylic acid: a trans-communic acid derivative

Nezha Rejouani; Aziz Auhmani; My Youssef Ait Itto; Ahmed Benharref; Jean-Claude Daran

doi:10.1107/S1600536808001086

. 2008 Jan 18;64(Pt 2):o475. doi: 10.1107/S1600536808001086

1,4a-Dimethyl-6-methylene-5-(5,5,6,6-tetracyano-2-methylcyclohex-2-enylmethyl)decahydronaphthalene-1-carboxylic acid: a trans-communic acid derivative

Nezha Rejouani ^a, Aziz Auhmani ^a, My Youssef Ait Itto ^a, Ahmed Benharref ^a, Jean-Claude Daran ^b,^*

PMCID: PMC2960367 PMID: 21201501

Abstract

In the search for cancer chemopreventive agents, we have studied the Diels–Alder reaction of trans-communic acid with tetracyanoethylene in the presence of SiO₂ as catalyst. The title cycloadduct, C₂₆H₃₀N₄O₂, was obtained in 75% yield. The molecules are arranged in pairs through O—H⋯O hydrogen bonds, forming an R ₂ ²(8) ring motif. Both the fused cyclohexyl rings adopt a chair conformation, whereas the nonfused ring adopts a half-chair conformation.

Related literature

For literature on anti-tumour activity, see: Bouhal et al. (1988 ▶); Iwamoto et al. (2001 ▶). For structural analyses, see: Etter et al. (1990 ▶); Bernstein et al. (1995 ▶); Cremer & Pople (1975 ▶). For the treatment of disordered solvent, see: Spek (2003 ▶).

Experimental

Crystal data

C₂₆H₃₀N₄O₂
M _r = 430.54
Monoclinic,
a = 30.664 (4) Å
b = 11.8233 (19) Å
c = 7.1857 (10) Å
β = 93.260 (12)°
V = 2600.9 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.07 mm⁻¹
T = 180 (2) K
0.52 × 0.08 × 0.07 mm

Data collection

Oxford Diffraction Xcalibur Sapphire-I diffractometer
Absorption correction: none
5114 measured reflections
2615 independent reflections
1302 reflections with I > 2σ(I)
R _int = 0.037

Refinement

R[F ² > 2σ(F ²)] = 0.037
wR(F ²) = 0.085
S = 0.82
2615 reflections
293 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.13 e Å⁻³
Δρ_min = −0.12 e Å⁻³

Data collection: CrysAlis CCD (Oxford Diffraction, 2006 ▶); cell refinement: CrysAlis RED (Oxford Diffraction, 2006 ▶); data reduction: CrysAlis RED; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); 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: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808001086/er2042sup1.cif

e-64-0o475-sup1.cif^{(21.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808001086/er2042Isup2.hkl

e-64-0o475-Isup2.hkl^{(125.8KB, 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
O9—H9⋯O9′ⁱ	0.84	1.79	2.631 (3)	178

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Symmetry code: (i) Inline graphic .

supplementary crystallographic information

Comment

Juniperus oxycedrus has been used in traditional folk medicine for the treatment of chronic eczema and other several skin diseases (Bouhal et al., 1988). Trans communic acid 1 is one of the compounds which were isolated from Juniperusoxycedrus and known by its moderate anti-tumor activity (Iwamoto et al., 2001). In the search for cancer chemo preventive agents with strong activity, we have studied the Diels-Alder reaction of trans communic acid 1 with tetracyanoethylene 2 in the presence of SiO₂ as catalyst (Fig.1). One cycloadduct 3 was obtained in 75% yield.

Its structure was identified as 1,4a-Dimethyl-6-methylene-5-(5,5,6,6-tetracyano-2-methylcyclohex-2-\ enylmethyl)-decahydronaphthalene-1-carboxylic acid using spectral methods including ¹H and ¹³C NMR and confirmed by an X-ray crystallographic analysis. The ¹H NMR spectrum of 3 exhibits three methyl singlets at 1.96, 1.29 and 0.69 p.p.m., a triplet (J=3 Hz, at 5.57ppm) due to proton H-3' and two singlets (at 4.50 and 5.08 p.p.m.) assigned to methylenic protons at 13 position. The ¹³C NMR spectra reveals twenty six signals including specially a carbonyl group at 183.36 p.p.m. and four cyano group signals at 109.19; 110.07; 110.94 and 111.54ppm.

The molecule is build up by two fused six cyclohexyl rings linked linked through a CH₂ spacer to a tetracyano-2-methylcyclohexyl ring (Fig. 2). The fused cyclohexyl rings, C1 to C8a and C4A to C8A, adopt a chair conformation as indicated by the puckering parameters [Q= 0.533 (6)°, 0.576 (6)° and θ= 0. 0(6)°, 0.4 (6)°, Cremer & Pople, (1975)]. The non fused cyclohexyl ring adopt a half-chair conformation[Q= 0.510 (6)° and θ= 50.7 (5)°]. The occurrence of O—H···O hydrogen bonds form pairs of molecules through a R²₂(8) ring motif (Etter et al., 1990; Bernstein et al., 1995) (Fig. 3).

Experimental

To a solution of Compound 1(1 g, 2.5 mmol) in 20 ml of dichloromethane, was added tetracyanoethylene (TCNE)(0.32 g, 2.5 mmol). The mixture was refluxed for 72 h. After cooling, the solvent was removed by evaporation under reduced pressure. The obtained residue was purified by chromatography on silica gel column (eluent: hexane/ethyl acetate 90/10), then the isolated product was recrystallized from ethyl acetate to give compound 3(750 mg, 75%).

Colourless crystal, mp=208–210°C (ethyl acetate). ¹H NMR (300 MHz, CDCl₃)δ (p.p.m.): 5.57 (t, 1H, J=4.45 Hz); 5.08 (s, 1H); 4.50 (s,1H); 3.28 (br d,1H, J=11.5 Hz); 3.00 (m, 2H); 2.48 (br d, 1H, J=11.5 Hz); 2.29–1.96 (m, 5H); 1.92 (s, 3H); 1.81 (m, 3H); 1.62 (m, 1H); 1.45 (dd, 1H, J=12.21 and 2.60); 1.29 (s, 3H); 1.26 (m, 2H); 1.15 (m, 1H); 0.69 (s, 3H). ¹³C NMR δ (p.p.m.) CDCl₃: 12.64 C11, 19.85 C3, 21.78 C7, 25.59 C8, 26.13 C4, 29.01 C9, 31.75 C12, 37.70 C2, 38.07 C4', 38.58 C7, 39.56 C4a, 41.37 C6', 41.74 C1', 43.41 C5', 44.29 C1, 51.63 C5, 56.47 C8a, 107.59 C13, 109.19 C8', 110.07 C9', 110.94 C10', 111.54 C11', 116.37 C3', 135.27 C6, 147.14 C2', 183.36 C10