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Crystal structure of olivetolic acid: a natural product from Cetrelia sanguinea (Schaer.)

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aThe Laboratory of Natural Resource of Sumatra (LBS) and Faculty of Pharmacy, Andalas University, 26163 Padang, Indonesia, and bDepartment of Chemistry and Materials Science, Tokyo Institute of Technology, Ookayama 2-12-1, Meguro-ku, Tokyo 152-8551, Japan
*Correspondence e-mail: uekusa@cms.titech.ac.jp

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 31 August 2016; accepted 13 October 2016; online 18 October 2016)

The title compound, C12H16O4 (systematic name: 2,4-dihy­droxy-6-pentyl­benzoic acid) is a natural product isolated from C. sanguinea (Schaer.) and is reported to have various pharmacological activities. The mol­ecule is approximately planar (r.m.s. deviation for the non-H atoms = 0.096 Å) and features an intra­molecular O—H⋯O hydrogen bond. In the crystal, each olivetolic acid mol­ecule is connected to three neighbours via O—H⋯O hydrogen bonds, generating (10-1) sheets. This crystal is essentially isostructural with a related resorcinolic acid with a longer alkyl chain.

1. Chemical context

Monoaromatic compounds from lichens have attracted a great inter­est in the pharmaceutical field due to their potential pharmacological activities such as anti­bacterial, anti­fungal, cytotoxic, and photoprotective activities (Gianini et al.,2008[Gianini, A. S., Marques, M. R., Carvalho, N. C. P. & Honda, N. K. (2008). Z. Naturforsch. Teil C, 63, 29-34.]: Stocker-Wörgötter, 2008[Stocker-Wörgötter, E. (2008). Nat. Prod. Rep. 25, 188-200.]; Ismed et al., 2012[Ismed, F., Lohézic-Le Dévéhat, F., Delalande, O., Sinbandhit, S., Bakhtiar, A. & Boustie, J. (2012). Fitoterapia, 83, 1693-1698.]). The title compound, C12H16O4, is a derivative of alkyl resorcinolic acid which is commonly found in certain species of lichens (Gomes et al., 2006[Gomes, A. T., Honda, N. K., Roese, F. M., Muzzi, R. M. & Sauer, L. (2006). Z. Naturforsch. Teil C, 61, 653-657.]).

[Scheme 1]

2. Structural commentary

The title compound (Fig. 1[link]) crystallizes with monoclinic metric symmetry and adopts a roughly planar conformation (r.m.s. deviation = 0.093 Å). All bond distances, angles and dihedral angles appear to be usual except the bond angle of C6—C5—C12 [124.61 (13)°] compared to the mean value and their standard deviation of selected 24 similar structures reported in Cambridge Structural Database (CSD, Version 5.37, Update 2 Feb 2016; Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]). In this case, the deviating bond angle may be a result of the strong intra­molecular O2—H2⋯O3 inter­action.

[Figure 1]
Figure 1
The mol­ecular structure of the title compound, showing 50% probability displacement ellipsoids.

3. Supra­molecular features

In the crystal, each mol­ecule is connected with three others (Fig. 2[link]): O1 acts as an O—H⋯O hydrogen bond donor while O2 is an O—H⋯O acceptor, forming a C11(6) infinite chain. In addition, an O4—H4⋯O3 carb­oxy­lic acid homodimer synthon is observed, generating an R22(8) loop. Together, these hydrogen bonds construct a layered architecture propagating in the (10[\overline{1}]) plane. Details of the hydrogen bonds are given in Table 1[link].

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O1—H1A⋯O2i 0.93 (2) 1.90 (2) 2.8168 (16) 169.6 (19)
O2—H2⋯O3 1.00 (3) 1.58 (3) 2.5043 (14) 152 (2)
O4—H4⋯O3ii 0.94 (3) 1.70 (3) 2.6368 (15) 177 (2)
Symmetry codes: (i) [-x+{\script{1\over 2}}, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]; (ii) -x, -y-1, -z.
[Figure 2]
Figure 2
A partial view of the packing in the title compound, showing the hydrogen-bonded chain structure, formed through O—H⋯O hydrogen bonds. Blue dashed lines indicate hydrogen bonds.

Inter­estingly, the title compound showed isostructurality with alkyl resorsinolic acid derivatives with longer alkyl chain of 6-n-penta­decyl-2,4-dihy­droxy-benzoic acid (Gadret et al., 1975[Gadret, M., Goursolle, M., Leger, J. M. & Colleter, J. C. (1975). Acta Cryst. B31, 2784-2788.]; refcode: PDCHBZ10). Both structures exhibited extremely similar hydrogen bond in resorsinolic acid shown in Fig. 3[link]a and 3b. Both crystal structures consist of a hydro­philic layer of the resorcinol acid moiety with hydrogen-bonding inter­actions, and a hydro­phobic layer of normal alkyl chains.

[Figure 3]
Figure 3
Crystal-packing views along b axis of (a) the title compound and (b) 6-n-penta­decyl-2,4-di­hydroxy­benzoic acid. Both structures possess isostructurality. The arrows indicate the one-dimensional hydrogen-bond chains involving resorsinolic acid.

4. Crystallization

Crystallization of the title compound was conducted by dissolving 700 mg of the isolate in an ethyl acetate–hexane solvent mixture (1:1). The solution was kept for one week at room temperature yielding colourless needles of the title compound.

5. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. All non-hydrogen atoms were refined anistropically. The hydrogen atoms of O hy­droxy and O carb­oxy­lic acid were located from a difference Fourier map and were refined isotropically. All other hydrogen atoms were located geometrically and refined as riding [Uiso = 1.5Uiso(C) for the terminal alkyl group and Uiso = 1.2Uiso(C) for other hydrogen atoms].

Table 2
Experimental details

Crystal data
Chemical formula C12H16O4
Mr 224.25
Crystal system, space group Monoclinic, P21/n
Temperature (K) 173
a, b, c (Å) 14.2527 (8), 4.7524 (3), 17.6489 (11)
β (°) 103.538 (4)
V3) 1162.22 (12)
Z 4
Radiation type Cu Kα
μ (mm−1) 0.79
Crystal size (mm) 0.12 × 0.10 × 0.10
 
Data collection
Diffractometer RIGAKU R-AXIS RAPID II
Absorption correction Multi-scan (ABSCOR; Higashi, 1995[Higashi, T. (1995). ABSCOR. Rigaku Corporation, Tokyo, Japan.])
Tmin, Tmax 0.789, 0.924
No. of measured, independent and observed [I > 2σ(I)] reflections 12627, 2087, 1762
Rint 0.036
(sin θ/λ)max−1) 0.602
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.045, 0.136, 1.14
No. of reflections 2087
No. of parameters 158
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.29, −0.18
Computer programs: PROCESS-AUTO (Rigaku, 1998[Rigaku (1998). PROCESS-AUTO. Rigaku Corporation, Tokyo, Japan.]), SHELXS2014 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]) and SHELXL2014 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. A71, 3-8.]).

Supporting information


Computing details top

Data collection: PROCESS-AUTO (Rigaku, 1998); cell refinement: PROCESS-AUTO (Rigaku, 1998); data reduction: PROCESS-AUTO (Rigaku, 1998); program(s) used to solve structure: SHELXS2014 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015).

2,4-Dihydroxy-6-pentylbenzoic acid top
Crystal data top
C12H16O4F(000) = 480
Mr = 224.25Dx = 1.282 Mg m3
Monoclinic, P21/nCu Kα radiation, λ = 1.54186 Å
a = 14.2527 (8) ÅCell parameters from 12628 reflections
b = 4.7524 (3) Åθ = 3.6–68.2°
c = 17.6489 (11) ŵ = 0.79 mm1
β = 103.538 (4)°T = 173 K
V = 1162.22 (12) Å3Block, colorless
Z = 40.12 × 0.10 × 0.10 mm
Data collection top
RIGAKU R-AXIS RAPID II
diffractometer
2087 independent reflections
Radiation source: rotating anode X-ray1762 reflections with I > 2σ(I)
Detector resolution: 10.0 pixels mm-1Rint = 0.036
ω–scanθmax = 68.2°, θmin = 3.6°
Absorption correction: multi-scan
(ABSCOR; Higashi, 1995)
h = 1717
Tmin = 0.789, Tmax = 0.924k = 55
12627 measured reflectionsl = 2021
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: none
R[F2 > 2σ(F2)] = 0.045Hydrogen site location: mixed
wR(F2) = 0.136H atoms treated by a mixture of independent and constrained refinement
S = 1.14 w = 1/[σ2(Fo2) + (0.0808P)2 + 0.1676P]
where P = (Fo2 + 2Fc2)/3
2087 reflections(Δ/σ)max < 0.001
158 parametersΔρmax = 0.29 e Å3
0 restraintsΔρmin = 0.18 e Å3
Special details top

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.38939 (8)0.5564 (2)0.16723 (7)0.0419 (3)
C10.32068 (11)0.2528 (3)0.06446 (9)0.0333 (4)
H10.37260.29830.04130.040*
H1A0.3901 (15)0.588 (4)0.2194 (14)0.060 (6)*
O20.09864 (8)0.0870 (2)0.17140 (6)0.0348 (3)
H20.0574 (18)0.059 (5)0.1389 (14)0.079 (7)*
C20.31656 (11)0.3787 (3)0.13488 (9)0.0321 (4)
C30.24081 (11)0.3235 (3)0.16913 (9)0.0317 (4)
H30.23700.41400.21630.038*
O30.03156 (7)0.2603 (2)0.06590 (6)0.0345 (3)
C40.17037 (10)0.1334 (3)0.13338 (8)0.0286 (4)
O40.10317 (8)0.3497 (2)0.03022 (6)0.0378 (3)
H40.0556 (18)0.491 (6)0.0410 (14)0.080 (7)*
C50.17377 (10)0.0040 (3)0.06311 (8)0.0275 (3)
C60.25149 (10)0.0639 (3)0.02743 (8)0.0287 (4)
C70.25914 (11)0.0625 (3)0.04994 (9)0.0336 (4)
H7A0.19810.02410.08870.040*
H7B0.26480.26920.04350.040*
C80.34233 (11)0.0400 (3)0.08352 (9)0.0368 (4)
H8A0.33960.24760.08790.044*
H8B0.40420.01090.04740.044*
C90.33918 (12)0.0863 (3)0.16340 (9)0.0374 (4)
H9A0.34260.29390.15870.045*
H9B0.27680.03770.19920.045*
C100.42080 (13)0.0161 (4)0.19841 (10)0.0454 (5)
H10A0.41850.22400.20150.054*
H10B0.48310.03730.16320.054*
C110.41710 (14)0.1014 (4)0.27894 (11)0.0516 (5)
H11A0.42150.30710.27620.077*
H11B0.47130.02650.29820.077*
H11C0.35620.04660.31450.077*
C120.09866 (10)0.2112 (3)0.03296 (8)0.0283 (3)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0439 (6)0.0464 (7)0.0368 (7)0.0190 (5)0.0123 (5)0.0070 (5)
C10.0333 (8)0.0361 (8)0.0328 (8)0.0048 (6)0.0128 (6)0.0029 (6)
O20.0348 (6)0.0417 (6)0.0319 (6)0.0064 (5)0.0160 (5)0.0050 (5)
C20.0332 (7)0.0317 (7)0.0307 (8)0.0051 (6)0.0061 (6)0.0033 (6)
C30.0372 (8)0.0312 (8)0.0270 (8)0.0014 (6)0.0081 (7)0.0017 (6)
O30.0350 (6)0.0378 (6)0.0342 (6)0.0084 (4)0.0151 (5)0.0036 (5)
C40.0300 (7)0.0292 (7)0.0278 (8)0.0010 (6)0.0094 (6)0.0048 (6)
O40.0409 (6)0.0421 (6)0.0350 (6)0.0140 (5)0.0182 (5)0.0108 (5)
C50.0297 (7)0.0273 (7)0.0267 (8)0.0001 (6)0.0089 (6)0.0041 (6)
C60.0309 (7)0.0285 (7)0.0271 (8)0.0006 (6)0.0076 (6)0.0054 (6)
C70.0363 (8)0.0352 (8)0.0327 (9)0.0053 (6)0.0148 (7)0.0004 (6)
C80.0381 (8)0.0414 (9)0.0348 (9)0.0073 (7)0.0161 (7)0.0018 (7)
C90.0399 (8)0.0406 (9)0.0362 (9)0.0048 (7)0.0179 (7)0.0009 (7)
C100.0467 (9)0.0509 (10)0.0457 (10)0.0076 (8)0.0253 (8)0.0038 (8)
C110.0581 (11)0.0594 (11)0.0462 (11)0.0007 (9)0.0299 (9)0.0023 (9)
C120.0310 (7)0.0279 (7)0.0271 (7)0.0004 (6)0.0090 (6)0.0034 (6)
Geometric parameters (Å, º) top
O1—C21.3563 (18)C6—C71.519 (2)
O1—H1A0.93 (2)C7—C81.5243 (19)
C1—C61.380 (2)C7—H7A0.9900
C1—C21.393 (2)C7—H7B0.9900
C1—H10.9500C8—C91.523 (2)
O2—C41.3657 (16)C8—H8A0.9900
O2—H21.00 (3)C8—H8B0.9900
C2—C31.380 (2)C9—C101.519 (2)
C3—C41.388 (2)C9—H9A0.9900
C3—H30.9500C9—H9B0.9900
O3—C121.2520 (16)C10—C111.516 (2)
C4—C51.412 (2)C10—H10A0.9900
O4—C121.3094 (17)C10—H10B0.9900
O4—H40.94 (3)C11—H11A0.9800
C5—C61.4333 (19)C11—H11B0.9800
C5—C121.460 (2)C11—H11C0.9800
C2—O1—H1A110.4 (13)C9—C8—C7112.14 (13)
C6—C1—C2121.82 (13)C9—C8—H8A109.2
C6—C1—H1119.1C7—C8—H8A109.2
C2—C1—H1119.1C9—C8—H8B109.2
C4—O2—H2103.8 (14)C7—C8—H8B109.2
O1—C2—C3122.28 (14)H8A—C8—H8B107.9
O1—C2—C1117.06 (13)C10—C9—C8113.00 (13)
C3—C2—C1120.66 (14)C10—C9—H9A109.0
C2—C3—C4118.78 (14)C8—C9—H9A109.0
C2—C3—H3120.6C10—C9—H9B109.0
C4—C3—H3120.6C8—C9—H9B109.0
O2—C4—C3115.27 (13)H9A—C9—H9B107.8
O2—C4—C5122.70 (13)C11—C10—C9113.66 (15)
C3—C4—C5122.02 (13)C11—C10—H10A108.8
C12—O4—H4110.8 (15)C9—C10—H10A108.8
C4—C5—C6118.06 (13)C11—C10—H10B108.8
C4—C5—C12117.30 (12)C9—C10—H10B108.8
C6—C5—C12124.61 (13)H10A—C10—H10B107.7
C1—C6—C5118.60 (13)C10—C11—H11A109.5
C1—C6—C7119.31 (13)C10—C11—H11B109.5
C5—C6—C7122.09 (13)H11A—C11—H11B109.5
C6—C7—C8116.69 (13)C10—C11—H11C109.5
C6—C7—H7A108.1H11A—C11—H11C109.5
C8—C7—H7A108.1H11B—C11—H11C109.5
C6—C7—H7B108.1O3—C12—O4119.78 (13)
C8—C7—H7B108.1O3—C12—C5122.09 (13)
H7A—C7—H7B107.3O4—C12—C5118.12 (12)
C6—C1—C2—O1178.54 (13)C12—C5—C6—C1176.44 (13)
C6—C1—C2—C31.8 (2)C4—C5—C6—C7177.26 (12)
O1—C2—C3—C4178.34 (14)C12—C5—C6—C74.3 (2)
C1—C2—C3—C42.0 (2)C1—C6—C7—C82.5 (2)
C2—C3—C4—O2179.08 (12)C5—C6—C7—C8176.74 (13)
C2—C3—C4—C50.2 (2)C6—C7—C8—C9176.33 (13)
O2—C4—C5—C6178.97 (12)C7—C8—C9—C10179.26 (14)
C3—C4—C5—C61.8 (2)C8—C9—C10—C11178.38 (15)
O2—C4—C5—C122.5 (2)C4—C5—C12—O32.4 (2)
C3—C4—C5—C12176.76 (13)C6—C5—C12—O3179.11 (13)
C2—C1—C6—C50.3 (2)C4—C5—C12—O4176.99 (12)
C2—C1—C6—C7179.01 (13)C6—C5—C12—O41.5 (2)
C4—C5—C6—C12.0 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1A···O2i0.93 (2)1.90 (2)2.8168 (16)169.6 (19)
O2—H2···O31.00 (3)1.58 (3)2.5043 (14)152 (2)
O4—H4···O3ii0.94 (3)1.70 (3)2.6368 (15)177 (2)
Symmetry codes: (i) x+1/2, y+1/2, z+1/2; (ii) x, y1, z.
 

Acknowledgements

We gratefully acknowledge Andalas University for financial support (contract No. 12/UN.16/HKRGB/LPPM/2016). Thanks also to Dr Harrie J. M. Sipman, Botanischer Garten und Botanisches Museum Berlin-Dahlem, Freie Universität Berlin, for the identification of the lichen. YPN and ODP wish to thank MEXT for research fellowships.

References

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