(2E,4R,5R,6S)-2-(4,5,6-Trihy­droxy­cyclo­hex-2-en-1-yl­idene)acetonitrile

Guedem, A.N.; Sandjo, L.P.; Opatz, T.; Schollmeyer, D.; Ngadjui, B.T.

doi:10.1107/S1600536812035313

organic compounds

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ISSN: 2056-9890

Volume 68| Part 9| September 2012| Page o2737

doi:10.1107/S1600536812035313

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(2E,4R,5R,6S)-2-(4,5,6-Trihydroxycyclohex-2-en-1-ylidene)acetonitrile

Alphonsine N. Guedem,^a Louis P. Sandjo,^b Till Opatz,^b Dieter Schollmeyer ^b and Bonaventure T. Ngadjui ^a ^*

^aDepartment of Organic Chemistry, University of Yaounde I, PO Box 812 Yaounde, Cameroon, and ^bUniversity Mainz, Duesbergweg 10-14, 55128 Mainz, Germany
^*Correspondence e-mail: ngadjuibt@yahoo.fr

(Received 11 July 2012; accepted 9 August 2012; online 23 August 2012)

The crystal structure of the title compound, C₈H₉NO₃, is characterized by a complex three-dimensional hydrogen-bond network in which every molecule is connected to six symmetry-related neighbours.

Related literature

For the isolation of this natural product, see: Hua et al. (2004 ). For previous phytochemical and biological studies of the stem bark of Thecacoris annobonae, see: Kuete et al. (2010 ).

Experimental

Crystal data

C₈H₉NO₃
M_r = 167.16
Monoclinic, P 2₁
a = 4.8159 (5) Å
b = 10.2482 (5) Å
c = 8.3573 (9) Å
β = 102.842 (4)°
V = 402.15 (6) Å³
Z = 2
Cu Kα radiation
μ = 0.90 mm⁻¹
T = 193 K
0.60 × 0.06 × 0.06 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
2174 measured reflections
1514 independent reflections
1501 reflections with I > 2σ(I)
R_int = 0.021
3 standard reflections every 60 min intensity decay: 5%

Refinement

R[F² > 2σ(F²)] = 0.026
wR(F²) = 0.071
S = 1.08
1514 reflections
146 parameters
1 restraint
All H-atom parameters refined
Δρ_max = 0.21 e Å⁻³
Δρ_min = −0.12 e Å⁻³
Absolute structure: Flack, (1983 )
Flack parameter: −0.04 (16)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O7—H7⋯O9ⁱ	0.79 (2)	1.93 (2)	2.6885 (14)	160 (2)
O8—H8⋯N12ⁱⁱ	0.77 (2)	2.18 (2)	2.9138 (16)	160 (2)
O9—H9⋯O7ⁱⁱⁱ	0.78 (3)	2.02 (2)	2.7944 (15)	170 (2)
Symmetry codes: (i) $[-x+2, y-{\script{1\over 2}}, -z+1]$ ; (ii) x+1, y, z+1; (iii) $[-x+1, y+{\script{1\over 2}}, -z+1]$ .

Data collection: CAD-4 Software (Enraf–Nonius, 1989 ); cell refinement: CAD-4 Software; data reduction: CORINC (Dräger & Gattow, 1971 ); program(s) used to solve structure: SIR97 (Altomare et al., 1999 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ); molecular graphics: PLATON (Spek, 2009 ); software used to prepare material for publication: PLATON.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536812035313/nc2287sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812035313/nc2287Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536812035313/nc2287Isup3.cml

checkCIF report

Comment top

Previous phytochemical and biological studies of the stem bark of Thecacoris annobonae (Euphorbiaceae) led to several bioactive secondary metabolites: Kuete et al. (2010). In the continuation of this investigation, the title compound was isolated from the leaves of the same plant using chromatographic methods and characterized by single crystal X-ray diffraction. It should be noted that this natural product was previously obtained from the root of Semiaquilegia adoxoides (Ranunculaceae): Hua et al. (2004).

In the crystal structure of the title compound the six membered ring adopts an envelope conformation in which C(3) is 0.678 (1) Å below the ring plane (Fig. 1). The acrylonitrile group is nearly coplanar to the least square plane of the ring system. The packing is characterized by a complex three-dimensional network formed by hydrogen bonds. Every molecule interacts by hydrogen bonds with six symmetry related molecules. While the hydroxyl groups O7 and O9 are both donor and acceptor of hydrogen bonds, O8 only interacts with N12 via hydrogen bonding (Fig. 2 and Table 1).

Related literature top

For the isolation of this natural product, see: Hua et al. (2004). For previous phytochemical and biological studies of the stem bark of Thecacoris annobonae, see: Kuete et al. (2010).

Experimental top

Air-dried powder of leaves of Thecacoris annobonae (1.37 kg) was successively macerated with hexane, ethyl acetate and methanol for two days each. Three fractions H (30 g), E (45 g), and M (61 g) were collected. The Methanol fraction M was subjected to a silica gel column chromatography eluted with CH₂Cl₂ to MeOH gradient yielding 7 mg of this secondary metabolite. It crystallized as needles in three of the fractions eluted with the mixture CH₂Cl₂/MeOH in a ratio of 97:3.

Computing details top

Data collection: CAD-4 Software (Enraf–Nonius, 1989); cell refinement: CAD-4 Software (Enraf–Nonius, 1989); data reduction: CORINC (Dräger & Gattow, 1971); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: PLATON (Spek, 2009).

Figures top

Fig. 1. Crystal structure of the title compound with labelling and displacement ellipsoids drawn at the 50% probability level.

Fig. 2. Crystal structure of the title compound with view along the a-axis. For calrity only H-atoms involved in hydrogen bonds are shown. Intermolecular hydrogen bonding is represented as dashed lines.

(2E,4R,5R,6S)-2-(4,5,6-Trihydroxycyclohex-2-en-1- ylidene)acetonitrile top

Crystal data top

C₈H₉NO₃	F(000) = 176
M_r = 167.16	D_x = 1.380 Mg m⁻³
Monoclinic, P2₁	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P 2yb	Cell parameters from 25 reflections
a = 4.8159 (5) Å	θ = 35–46°
b = 10.2482 (5) Å	µ = 0.90 mm⁻¹
c = 8.3573 (9) Å	T = 193 K
β = 102.842 (4)°	Needle, colourless
V = 402.15 (6) Å³	0.60 × 0.06 × 0.06 mm
Z = 2

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0.021
Radiation source: rotating anode	θ_max = 70.0°, θ_min = 5.4°
Graphite monochromator	h = −5→5
ω/2θ scans	k = −12→12
2174 measured reflections	l = −10→10
1514 independent reflections	3 standard reflections every 60 min
1501 reflections with I > 2σ(I)	intensity decay: 5%

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	All H-atom parameters refined
R[F² > 2σ(F²)] = 0.026	w = 1/[σ²(F_o²) + (0.0474P)² + 0.0306P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.071	(Δ/σ)_max < 0.001
S = 1.08	Δρ_max = 0.21 e Å⁻³
1514 reflections	Δρ_min = −0.12 e Å⁻³
146 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
1 restraint	Extinction coefficient: 0.018 (3)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack, (1983)
Secondary atom site location: difference Fourier map	Absolute structure parameter: −0.04 (16)

Crystal data top

C₈H₉NO₃	V = 402.15 (6) Å³
M_r = 167.16	Z = 2
Monoclinic, P2₁	Cu Kα radiation
a = 4.8159 (5) Å	µ = 0.90 mm⁻¹
b = 10.2482 (5) Å	T = 193 K
c = 8.3573 (9) Å	0.60 × 0.06 × 0.06 mm
β = 102.842 (4)°

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0.021
2174 measured reflections	3 standard reflections every 60 min
1514 independent reflections	intensity decay: 5%
1501 reflections with I > 2σ(I)

Refinement top

R[F² > 2σ(F²)] = 0.026	All H-atom parameters refined
wR(F²) = 0.071	Δρ_max = 0.21 e Å⁻³
S = 1.08	Δρ_min = −0.12 e Å⁻³
1514 reflections	Absolute structure: Flack, (1983)
146 parameters	Absolute structure parameter: −0.04 (16)
1 restraint

Special details top

Experimental. ¹H–, ¹³C– and two-dimensional-NMR spectra were recorded on Bruker AVANCE II-400 MHz s pectrometer equipped with a 5 mm observe probe and a z-gradient coil using standard pulse sequences. HR-ESI-MS was carried out on a Waters Q-TOF Ultima III mass spectrometer. HR-ESI-MS m/z 190.0470 (calcd. for [C₈H₉NO₃+Na]⁺ 190.0475); NMR (¹H-NMR, 400 MHz, acetone-d₆): 6.55 (1H, dd, J = 2.5, 10.1 Hz, H-2), 6.04 (1H, dd, J = 1.8, 10.1 Hz, H-3), 4.11–4.16 (1H, m, H-4), 4.40–4.44 (1H, m, H-5), 4.44–4.50 (1H, m, H-6), 5.63 (1H, s, H-7), 4.60 (1H, d, J = 7.9 Hz, OH-5), 4.16–4.18 (2H, m, OH-4 and 6); (¹³C-NMR, 100 MHz, acetone-d₆): 159.7 (C-1), 124.0 (C-2), 139.6 (C-3), 74.5 (C-4), 69.6 (C-5), 71.9 (C-6),93.7 (C-7), 117.6 (C-8).

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.4167 (3)	0.60278 (13)	0.16499 (15)	0.0204 (3)
C2	0.6543 (3)	0.54538 (12)	0.29376 (15)	0.0193 (3)
H2	0.822 (3)	0.5471 (15)	0.2490 (18)	0.014 (3)*
C3	0.7220 (3)	0.63193 (13)	0.44623 (15)	0.0195 (3)
H3	0.881 (4)	0.5923 (17)	0.525 (2)	0.023 (4)*
C4	0.8147 (3)	0.76563 (13)	0.39626 (17)	0.0244 (3)
H4	0.992 (4)	0.7516 (17)	0.364 (2)	0.023 (4)*
C5	0.6001 (3)	0.81945 (14)	0.2530 (2)	0.0291 (3)
H5	0.591 (4)	0.911 (2)	0.238 (2)	0.041 (5)*
C6	0.4214 (3)	0.74407 (14)	0.14727 (17)	0.0277 (3)
H6	0.289 (4)	0.7814 (18)	0.059 (2)	0.023 (4)*
O7	0.5884 (2)	0.41531 (9)	0.32843 (12)	0.0246 (2)
H7	0.730 (5)	0.381 (2)	0.375 (2)	0.038 (5)*
O8	0.47685 (18)	0.64281 (10)	0.51340 (11)	0.0221 (2)
H8	0.530 (4)	0.644 (2)	0.607 (3)	0.031 (5)*
O9	0.8700 (2)	0.85292 (10)	0.53125 (14)	0.0320 (3)
H9	0.730 (5)	0.870 (2)	0.559 (3)	0.045 (6)*
C10	0.2197 (3)	0.52459 (15)	0.07211 (16)	0.0252 (3)
H10	0.220 (4)	0.431 (2)	0.0850 (19)	0.024 (4)*
C11	−0.0065 (3)	0.57476 (17)	−0.05275 (17)	0.0316 (3)
N12	−0.1938 (3)	0.61195 (18)	−0.15135 (17)	0.0451 (4)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0145 (6)	0.0289 (7)	0.0186 (5)	0.0032 (5)	0.0053 (4)	0.0007 (5)
C2	0.0106 (6)	0.0241 (6)	0.0233 (6)	0.0012 (5)	0.0043 (5)	0.0010 (5)
C3	0.0086 (5)	0.0255 (6)	0.0227 (5)	0.0031 (4)	−0.0001 (4)	0.0005 (5)
C4	0.0128 (6)	0.0260 (7)	0.0344 (7)	−0.0030 (5)	0.0054 (5)	−0.0046 (5)
C5	0.0271 (8)	0.0222 (7)	0.0391 (8)	−0.0003 (5)	0.0098 (6)	0.0065 (5)
C6	0.0229 (7)	0.0318 (8)	0.0273 (6)	0.0039 (6)	0.0034 (5)	0.0097 (6)
O7	0.0167 (5)	0.0204 (5)	0.0340 (5)	0.0034 (4)	−0.0001 (4)	0.0022 (4)
O8	0.0134 (4)	0.0328 (5)	0.0197 (4)	0.0006 (4)	0.0030 (3)	−0.0018 (4)
O9	0.0135 (5)	0.0332 (6)	0.0489 (6)	−0.0054 (4)	0.0060 (4)	−0.0162 (5)
C10	0.0186 (6)	0.0354 (7)	0.0212 (6)	0.0016 (5)	0.0034 (5)	−0.0014 (5)
C11	0.0250 (7)	0.0477 (9)	0.0208 (6)	−0.0052 (6)	0.0024 (6)	−0.0037 (6)
N12	0.0319 (7)	0.0705 (11)	0.0269 (6)	0.0011 (7)	−0.0064 (5)	0.0055 (6)

Geometric parameters (Å, º) top

C1—C10	1.3479 (19)	C4—H4	0.963 (18)
C1—C6	1.4563 (19)	C5—C6	1.334 (2)
C1—C2	1.5054 (16)	C5—H5	0.94 (2)
C2—O7	1.4151 (15)	C6—H6	0.943 (18)
C2—C3	1.5272 (17)	O7—H7	0.79 (2)
C2—H2	0.962 (16)	O8—H8	0.77 (2)
C3—O8	1.4200 (16)	O9—H9	0.78 (3)
C3—C4	1.5277 (18)	C10—C11	1.426 (2)
C3—H3	0.981 (17)	C10—H10	0.96 (2)
C4—O9	1.4178 (17)	C11—N12	1.144 (2)
C4—C5	1.5019 (19)

C10—C1—C6	123.87 (12)	C5—C4—C3	110.86 (10)
C10—C1—C2	120.34 (12)	O9—C4—H4	107.3 (10)
C6—C1—C2	115.77 (11)	C5—C4—H4	109.1 (10)
O7—C2—C1	110.18 (11)	C3—C4—H4	105.9 (10)
O7—C2—C3	113.10 (10)	C6—C5—C4	122.94 (13)
C1—C2—C3	110.92 (10)	C6—C5—H5	119.0 (12)
O7—C2—H2	110.0 (10)	C4—C5—H5	118.1 (12)
C1—C2—H2	106.6 (9)	C5—C6—C1	122.05 (12)
C3—C2—H2	105.8 (9)	C5—C6—H6	120.6 (11)
O8—C3—C2	109.47 (10)	C1—C6—H6	117.4 (11)
O8—C3—C4	110.90 (11)	C2—O7—H7	108.3 (16)
C2—C3—C4	108.30 (10)	C3—O8—H8	106.5 (14)
O8—C3—H3	111.0 (10)	C4—O9—H9	111.1 (17)
C2—C3—H3	108.2 (10)	C1—C10—C11	122.16 (14)
C4—C3—H3	108.9 (10)	C1—C10—H10	123.0 (10)
O9—C4—C5	112.14 (12)	C11—C10—H10	114.9 (10)
O9—C4—C3	111.28 (11)	N12—C11—C10	177.70 (18)

C10—C1—C2—O7	−16.29 (16)	O8—C3—C4—C5	−68.05 (13)
C6—C1—C2—O7	165.07 (11)	C2—C3—C4—C5	52.09 (14)
C10—C1—C2—C3	−142.30 (13)	O9—C4—C5—C6	−149.07 (14)
C6—C1—C2—C3	39.06 (15)	C3—C4—C5—C6	−24.01 (19)
O7—C2—C3—O8	−63.88 (13)	C4—C5—C6—C1	1.4 (2)
C1—C2—C3—O8	60.49 (13)	C10—C1—C6—C5	172.38 (14)
O7—C2—C3—C4	175.09 (9)	C2—C1—C6—C5	−9.0 (2)
C1—C2—C3—C4	−60.54 (13)	C6—C1—C10—C11	−0.6 (2)
O8—C3—C4—O9	57.48 (13)	C2—C1—C10—C11	−179.10 (12)
C2—C3—C4—O9	177.62 (10)	C1—C10—C11—N12	−141 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O7—H7···O9ⁱ	0.79 (2)	1.93 (2)	2.6885 (14)	160 (2)
O8—H8···N12ⁱⁱ	0.77 (2)	2.18 (2)	2.9138 (16)	160 (2)
O9—H9···O7ⁱⁱⁱ	0.78 (3)	2.02 (2)	2.7944 (15)	170 (2)

Symmetry codes: (i) −x+2, y−1/2, −z+1; (ii) x+1, y, z+1; (iii) −x+1, y+1/2, −z+1.

Experimental details

Crystal data
Chemical formula	C₈H₉NO₃
M_r	167.16
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	193
a, b, c (Å)	4.8159 (5), 10.2482 (5), 8.3573 (9)
β (°)	102.842 (4)
V (Å³)	402.15 (6)
Z	2
Radiation type	Cu Kα
µ (mm⁻¹)	0.90
Crystal size (mm)	0.60 × 0.06 × 0.06

Data collection
Diffractometer	Enraf–Nonius CAD-4 diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	2174, 1514, 1501
R_int	0.021
(sin θ/λ)_max (Å⁻¹)	0.609

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.026, 0.071, 1.08
No. of reflections	1514
No. of parameters	146
No. of restraints	1
H-atom treatment	All H-atom parameters refined
Δρ_max, Δρ_min (e Å⁻³)	0.21, −0.12
Absolute structure	Flack, (1983)
Absolute structure parameter	−0.04 (16)

Computer programs: CAD-4 Software (Enraf–Nonius, 1989), CORINC (Dräger & Gattow, 1971), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O7—H7···O9ⁱ	0.79 (2)	1.93 (2)	2.6885 (14)	160 (2)
O8—H8···N12ⁱⁱ	0.77 (2)	2.18 (2)	2.9138 (16)	160 (2)
O9—H9···O7ⁱⁱⁱ	0.78 (3)	2.02 (2)	2.7944 (15)	170 (2)

Symmetry codes: (i) −x+2, y−1/2, −z+1; (ii) x+1, y, z+1; (iii) −x+1, y+1/2, −z+1.

Acknowledgements

We thank Dr J. C. Liermann (Mainz) for performing the NMR spectroscopy.

References

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