Crystal structure of 2-[(1R,2R,4aS,8aS)-2-hy­droxy-2,5,5,8a-tetra­methyl­deca­hydro­naphthalen-1-yl]-N-(o-tol­yl)acetamide

Dang-Dang Li; Xin-Wei Shi; Qiang-Qiang Lu; Sheng-Kun Li

doi:10.1107/S2056989015017600

. 2015 Sep 26;71(Pt 10):o788–o789. doi: 10.1107/S2056989015017600

Crystal structure of 2-[(1R,2R,4aS,8aS)-2-hydroxy-2,5,5,8a-tetramethyldecahydronaphthalen-1-yl]-N-(o-tolyl)acetamide

Dang-Dang Li ^a, Xin-Wei Shi ^b, Qiang-Qiang Lu ^b, Sheng-Kun Li ^a,^*

PMCID: PMC4647428 PMID: 26594480

Abstract

The title compound, C₂₃H₃₅NO₂, is an amide derivative of the lactone (+)-sclareolide, and was synthesized from natural sclareol. In the molecular structure, the two six-membered rings (A and B) of the labdane skeleton are trans-fused, and adopt chair conformations. There is an intramolecular N—H⋯O hydrogen bond present forming an S(7) ring motif. In the crystal, O—H⋯O hydrogen bonds link the molecules into helical chains propagating along the b-axis direction. The chains are linked via C—H⋯π interactions, forming a three-dimensional structure.

Keywords: crystal structure, sclareolide, sclareol, hydrogen bonding, C—H⋯π interactions

Related literature

For the chemistry and biological importance of sclareol and sclareolide, see: Barrero et al. (2004 ▸); Huang et al. (2001 ▸); Mohamad et al. (2005 ▸); Sy & Brown (1997 ▸). For the synthesis of coronarin and chinensines, see: Margaros & Vassilikogiannakis (2007 ▸). For related structures, see: Bernardinelli & Giersch (1985 ▸); Shi et al. (2015 ▸). graphic file with name e-71-0o788-scheme1.jpg

Experimental

Crystal data

C₂₃H₃₅NO₂
M _r = 357.52
Monoclinic,
a = 6.3001 (5) Å
b = 13.2663 (10) Å
c = 12.7082 (10) Å
β = 96.983 (2)°
V = 1054.26 (14) Å³
Z = 2
Mo Kα radiation
μ = 0.07 mm⁻¹
T = 296 K
0.22 × 0.20 × 0.18 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2002 ▸) T _min = 0.985, T _max = 0.987
3714 measured reflections
3714 independent reflections
3121 reflections with I > 2σ(I)
R _int = 0.020

Refinement

R[F ² > 2σ(F ²)] = 0.040
wR(F ²) = 0.095
S = 1.06
3714 reflections
242 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.11 e Å⁻³
Δρ_min = −0.13 e Å⁻³

Data collection: SMART (Bruker, 2002 ▸); cell refinement: SAINT (Bruker, 2002 ▸); 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 datablock(s) I, New_Global_Publ_Block. DOI: 10.1107/S2056989015017600/su5209sup1.cif

e-71-0o788-sup1.cif^{(31.3KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015017600/su5209Isup2.hkl

e-71-0o788-Isup2.hkl^{(185.7KB, hkl)}

Click here for additional data file.^{(3.7KB, cdx)}

Supporting information file. DOI: 10.1107/S2056989015017600/su5209Isup3.cdx

Click here for additional data file.^{(1.6MB, tif)}

. DOI: 10.1107/S2056989015017600/su5209fig1.tif

A view of the molecular structure of the title compound, with atom labelling. Displacement ellipsoids are drawn at the 30% probability level. The intramolecular N—H⋯O hydrogen bonds is shown as a dashed line (see Table 1).

Click here for additional data file.^{(3.9MB, tif)}

a . DOI: 10.1107/S2056989015017600/su5209fig2.tif

Crystal packing of the title compound, viewed along the a axis. The hydrogen bonds are shown as dashed lines (see Table 1), and C-bound H atoms have been omitted for clarity.

CCDC reference: 1426216

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (, ).

Cg is the centroid of benzene ring C1C6.

DHA	DH	HA	D A	DHA
N1H1O1	0.86	2.09	2.894(2)	155
O1H1OO2ⁱ	0.82	2.00	2.8054(19)	168
C8H8B Cg ⁱⁱ	0.97	2.79	3.632(2)	146
C22H22A Cg ⁱⁱⁱ	0.96	2.98	3.808(3)	145

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

Acknowledgments

This project was supported by the National Natural Science Foundation of China (Nos. 3140177 and 31200257), the Science and Technology Research and Development Projects of Shaanxi Province (No. 2013KJXX-74) and the National Science Foundation of Jiangsu Province (No. BK20140684).

supplementary crystallographic information

S1. Comment

The title compound, possessing an intact homodrimane skeleton, is an amide derivative of (+)-sclareolide, which was synthesized from natural sclareol (Barrero et al., 2004). The commercially available diterpene (-)-sclareol or the lactone derivative (+)-sclareolide make an ideal starting point for some biologically important natural products (Mohamad et al., 2005). Furthermore, the enantiometrically pure sclareolide provided the perfect tool to validate the absolute stereochemistry of certain chinensine family members, whose stereochemistry had been tentatively assigned based on comparisons to other biogenetically close compounds, such as coronarin E (Margaros & Vassilikogiannakis, 2007; Sy & Brown, 1997). Herein, we report on the first synthesis and crystal structure of the title compound.

The molecular structure of the title compound is shown in Fig. 1. The molecule is composed of three main rings (A, B and C). The six-membered rings, A (C13/C14/C17—C20) and B (C9—C14), are trans-fused and have chair conformations. Bond angles to the aliphatic rings and to the aromatic ring C (C1—C6) are in the range of 114.40 (16) to 129.65 (16)° and 117.91 (19) to 122.2 (2)°, respectively. The methyl group at C15 and the side chain at C8 are attached in ideal equatorial positions. There is an intramolecular N—H···O hydrogen bond forming an S(7) ring motif (Table 1).

In the crystal, O—H···O hydrogen bonds link the molecules into zigzag chains propagating along the b axis direction (Table 1 and Fig. 2). The chains are linked via C—H···π interactions forming a three-dimensional structure (Table 1).

S2. Synthesis and crystallization

A solution of DIBAL-H (1.5 M in toluene, 2.58 ml, 3.87 mmol) was added to a cooled (273 K) solution of o-methylanilines (0.688 g, 4.0 mmol) in THF (1.7 ml) under nitrogen. The mixture was allowed to warm up and stirred at rt for 2 h. The concentration of the prepared DIBAL-H-o-CH₃C₆H₄NH₂ complex was ca 0.88 M, and was used directly for aminolysis. To a solution of (+)-sclareolide (0.168 g, 0.67 mmol) in THF (2.5 ml) was added, under nitrogen at rt, the DIBAL-H-p-C₆H₄NH₂ complexe (3.8 ml, 3.35 mmol). After stirring at rt for 2 h, the reaction was cooled to 273 K, and then quenched with H₂O (1.5 ml) and a 1 M aqueous solution of KHSO₄ (4 ml). The resulting mixture was extracted with CH₂Cl₂ (3 × 10 ml). The combined organic layers were washed with brine, dried over Na₂SO₄ and concentrated. The residue was purified by flash chromatography (200-300 m ilicon) with PE/EtOAc = 6:1 as eluant to give the title compound (215 mg, yield 90 %) as a white solid (Margaros & Georgios, 2007). Colourless crystals were obtained by slow evaporation of a solution in CH₂Cl₂.

S2.1. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. All the H atoms could be located in difference Fourier maps. In the final cycles of refinement they were included in calculated positions and refined as riding atoms: O—H = 0.82 Å, N—H = 0.86 Å and C—H = 0.93-0.97 Å with U_iso(H) = 1.5U_eq(C) for OH and methyl H atoms and 1.2U_eq(N,C) for other H atoms. The absolute configuration of the title compound is based on that of the starting reagent (+)-sclareolide.