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

Ismed, F.; Farhan, A.; Bakhtiar, A.; Zaini, E.; Nugraha, Y.P.; Dwichandra Putra, O.; Uekusa, H.

doi:10.1107/S2056989016016273

research communications

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Volume 72| Part 11| November 2016| Pages 1587-1589

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

Friardi Ismed,^a Aulia Farhan,^a Amri Bakhtiar,^a Erizal Zaini,^a Yuda Prasetya Nugraha,^b Okky Dwichandra Putra ^b and Hidehiro Uekusa ^b ^*

^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.

Keywords: crystal structure; olivetolic acid; Cetrelia sanguinea.

CCDC reference: 1509626

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 : Stocker-Wörgötter, 2008 ; Ismed et al., 2012 ). The title compound, C₁₂H₁₆O₄, is a derivative of alkyl resorcinolic acid which is commonly found in certain species of lichens (Gomes et al., 2006 ).

2. Structural commentary

The title compound (Fig. 1) 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 ). In this case, the deviating bond angle may be a result of the strong intramolecular O2—H2⋯O3 interaction.

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): 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.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	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
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 ; refcode: PDCHBZ10). Both structures exhibited extremely similar hydrogen bond in resorsinolic acid shown in Fig. 3a 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
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. 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 [U_iso = 1.5U_iso(C) for the terminal alkyl group and U_iso = 1.2U_iso(C) for other hydrogen atoms].

Table 2
Experimental details

Crystal data
Chemical formula	C₁₂H₁₆O₄
M_r	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)
V (Å³)	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 )
T_min, T_max	0.789, 0.924
No. of measured, independent and observed [I > 2σ(I)] reflections	12627, 2087, 1762
R_int	0.036
(sin θ/λ)_max (Å⁻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
Δρ_max, Δρ_min (e Å⁻³)	0.29, −0.18
Computer programs: PROCESS-AUTO (Rigaku, 1998 ), SHELXS2014 (Sheldrick, 2008 ) and SHELXL2014 (Sheldrick, 2015 ).

Supporting information

CCDC reference: 1509626

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989016016273/hb7614sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989016016273/hb7614Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989016016273/hb7614Isup3.cml

checkCIF report

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

C₁₂H₁₆O₄	F(000) = 480
M_r = 224.25	D_x = 1.282 Mg m⁻³
Monoclinic, P2₁/n	Cu Kα radiation, λ = 1.54186 Å
a = 14.2527 (8) Å	Cell parameters from 12628 reflections
b = 4.7524 (3) Å	θ = 3.6–68.2°
c = 17.6489 (11) Å	µ = 0.79 mm⁻¹
β = 103.538 (4)°	T = 173 K
V = 1162.22 (12) Å³	Block, colorless
Z = 4	0.12 × 0.10 × 0.10 mm

Data collection top

RIGAKU R-AXIS RAPID II diffractometer	2087 independent reflections
Radiation source: rotating anode X-ray	1762 reflections with I > 2σ(I)
Detector resolution: 10.0 pixels mm^-1	R_int = 0.036
ω–scan	θ_max = 68.2°, θ_min = 3.6°
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	h = −17→17
T_min = 0.789, T_max = 0.924	k = −5→5
12627 measured reflections	l = −20→21

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: none
R[F² > 2σ(F²)] = 0.045	Hydrogen site location: mixed
wR(F²) = 0.136	H atoms treated by a mixture of independent and constrained refinement
S = 1.14	w = 1/[σ²(F_o²) + (0.0808P)² + 0.1676P] where P = (F_o² + 2F_c²)/3
2087 reflections	(Δ/σ)_max < 0.001
158 parameters	Δρ_max = 0.29 e Å⁻³
0 restraints	Δρ_min = −0.18 e Å⁻³

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

	x	y	z	U_iso*/U_eq
O1	0.38939 (8)	0.5564 (2)	0.16723 (7)	0.0419 (3)
C1	0.32068 (11)	0.2528 (3)	0.06446 (9)	0.0333 (4)
H1	0.3726	0.2983	0.0413	0.040*
H1A	0.3901 (15)	0.588 (4)	0.2194 (14)	0.060 (6)*
O2	0.09864 (8)	0.0870 (2)	0.17140 (6)	0.0348 (3)
H2	0.0574 (18)	−0.059 (5)	0.1389 (14)	0.079 (7)*
C2	0.31656 (11)	0.3787 (3)	0.13488 (9)	0.0321 (4)
C3	0.24081 (11)	0.3235 (3)	0.16913 (9)	0.0317 (4)
H3	0.2370	0.4140	0.2163	0.038*
O3	0.03156 (7)	−0.2603 (2)	0.06590 (6)	0.0345 (3)
C4	0.17037 (10)	0.1334 (3)	0.13338 (8)	0.0286 (4)
O4	0.10317 (8)	−0.3497 (2)	−0.03022 (6)	0.0378 (3)
H4	0.0556 (18)	−0.491 (6)	−0.0410 (14)	0.080 (7)*
C5	0.17377 (10)	−0.0040 (3)	0.06311 (8)	0.0275 (3)
C6	0.25149 (10)	0.0639 (3)	0.02743 (8)	0.0287 (4)
C7	0.25914 (11)	−0.0625 (3)	−0.04994 (9)	0.0336 (4)
H7A	0.1981	−0.0241	−0.0887	0.040*
H7B	0.2648	−0.2692	−0.0435	0.040*
C8	0.34233 (11)	0.0400 (3)	−0.08352 (9)	0.0368 (4)
H8A	0.3396	0.2476	−0.0879	0.044*
H8B	0.4042	−0.0109	−0.0474	0.044*
C9	0.33918 (12)	−0.0863 (3)	−0.16340 (9)	0.0374 (4)
H9A	0.3426	−0.2939	−0.1587	0.045*
H9B	0.2768	−0.0377	−0.1992	0.045*
C10	0.42080 (13)	0.0161 (4)	−0.19841 (10)	0.0454 (5)
H10A	0.4185	0.2240	−0.2015	0.054*
H10B	0.4831	−0.0373	−0.1632	0.054*
C11	0.41710 (14)	−0.1014 (4)	−0.27894 (11)	0.0516 (5)
H11A	0.4215	−0.3071	−0.2762	0.077*
H11B	0.4713	−0.0265	−0.2982	0.077*
H11C	0.3562	−0.0466	−0.3145	0.077*
C12	0.09866 (10)	−0.2112 (3)	0.03296 (8)	0.0283 (3)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0439 (6)	0.0464 (7)	0.0368 (7)	−0.0190 (5)	0.0123 (5)	−0.0070 (5)
C1	0.0333 (8)	0.0361 (8)	0.0328 (8)	−0.0048 (6)	0.0128 (6)	0.0029 (6)
O2	0.0348 (6)	0.0417 (6)	0.0319 (6)	−0.0064 (5)	0.0160 (5)	−0.0050 (5)
C2	0.0332 (7)	0.0317 (7)	0.0307 (8)	−0.0051 (6)	0.0061 (6)	0.0033 (6)
C3	0.0372 (8)	0.0312 (8)	0.0270 (8)	−0.0014 (6)	0.0081 (7)	−0.0017 (6)
O3	0.0350 (6)	0.0378 (6)	0.0342 (6)	−0.0084 (4)	0.0151 (5)	−0.0036 (5)
C4	0.0300 (7)	0.0292 (7)	0.0278 (8)	0.0010 (6)	0.0094 (6)	0.0048 (6)
O4	0.0409 (6)	0.0421 (6)	0.0350 (6)	−0.0140 (5)	0.0182 (5)	−0.0108 (5)
C5	0.0297 (7)	0.0273 (7)	0.0267 (8)	−0.0001 (6)	0.0089 (6)	0.0041 (6)
C6	0.0309 (7)	0.0285 (7)	0.0271 (8)	−0.0006 (6)	0.0076 (6)	0.0054 (6)
C7	0.0363 (8)	0.0352 (8)	0.0327 (9)	−0.0053 (6)	0.0148 (7)	0.0004 (6)
C8	0.0381 (8)	0.0414 (9)	0.0348 (9)	−0.0073 (7)	0.0161 (7)	−0.0018 (7)
C9	0.0399 (8)	0.0406 (9)	0.0362 (9)	−0.0048 (7)	0.0179 (7)	−0.0009 (7)
C10	0.0467 (9)	0.0509 (10)	0.0457 (10)	−0.0076 (8)	0.0253 (8)	−0.0038 (8)
C11	0.0581 (11)	0.0594 (11)	0.0462 (11)	−0.0007 (9)	0.0299 (9)	0.0023 (9)
C12	0.0310 (7)	0.0279 (7)	0.0271 (7)	−0.0004 (6)	0.0090 (6)	0.0034 (6)

Geometric parameters (Å, º) top

O1—C2	1.3563 (18)	C6—C7	1.519 (2)
O1—H1A	0.93 (2)	C7—C8	1.5243 (19)
C1—C6	1.380 (2)	C7—H7A	0.9900
C1—C2	1.393 (2)	C7—H7B	0.9900
C1—H1	0.9500	C8—C9	1.523 (2)
O2—C4	1.3657 (16)	C8—H8A	0.9900
O2—H2	1.00 (3)	C8—H8B	0.9900
C2—C3	1.380 (2)	C9—C10	1.519 (2)
C3—C4	1.388 (2)	C9—H9A	0.9900
C3—H3	0.9500	C9—H9B	0.9900
O3—C12	1.2520 (16)	C10—C11	1.516 (2)
C4—C5	1.412 (2)	C10—H10A	0.9900
O4—C12	1.3094 (17)	C10—H10B	0.9900
O4—H4	0.94 (3)	C11—H11A	0.9800
C5—C6	1.4333 (19)	C11—H11B	0.9800
C5—C12	1.460 (2)	C11—H11C	0.9800

C2—O1—H1A	110.4 (13)	C9—C8—C7	112.14 (13)
C6—C1—C2	121.82 (13)	C9—C8—H8A	109.2
C6—C1—H1	119.1	C7—C8—H8A	109.2
C2—C1—H1	119.1	C9—C8—H8B	109.2
C4—O2—H2	103.8 (14)	C7—C8—H8B	109.2
O1—C2—C3	122.28 (14)	H8A—C8—H8B	107.9
O1—C2—C1	117.06 (13)	C10—C9—C8	113.00 (13)
C3—C2—C1	120.66 (14)	C10—C9—H9A	109.0
C2—C3—C4	118.78 (14)	C8—C9—H9A	109.0
C2—C3—H3	120.6	C10—C9—H9B	109.0
C4—C3—H3	120.6	C8—C9—H9B	109.0
O2—C4—C3	115.27 (13)	H9A—C9—H9B	107.8
O2—C4—C5	122.70 (13)	C11—C10—C9	113.66 (15)
C3—C4—C5	122.02 (13)	C11—C10—H10A	108.8
C12—O4—H4	110.8 (15)	C9—C10—H10A	108.8
C4—C5—C6	118.06 (13)	C11—C10—H10B	108.8
C4—C5—C12	117.30 (12)	C9—C10—H10B	108.8
C6—C5—C12	124.61 (13)	H10A—C10—H10B	107.7
C1—C6—C5	118.60 (13)	C10—C11—H11A	109.5
C1—C6—C7	119.31 (13)	C10—C11—H11B	109.5
C5—C6—C7	122.09 (13)	H11A—C11—H11B	109.5
C6—C7—C8	116.69 (13)	C10—C11—H11C	109.5
C6—C7—H7A	108.1	H11A—C11—H11C	109.5
C8—C7—H7A	108.1	H11B—C11—H11C	109.5
C6—C7—H7B	108.1	O3—C12—O4	119.78 (13)
C8—C7—H7B	108.1	O3—C12—C5	122.09 (13)
H7A—C7—H7B	107.3	O4—C12—C5	118.12 (12)

C6—C1—C2—O1	178.54 (13)	C12—C5—C6—C1	−176.44 (13)
C6—C1—C2—C3	−1.8 (2)	C4—C5—C6—C7	−177.26 (12)
O1—C2—C3—C4	−178.34 (14)	C12—C5—C6—C7	4.3 (2)
C1—C2—C3—C4	2.0 (2)	C1—C6—C7—C8	−2.5 (2)
C2—C3—C4—O2	179.08 (12)	C5—C6—C7—C8	176.74 (13)
C2—C3—C4—C5	−0.2 (2)	C6—C7—C8—C9	−176.33 (13)
O2—C4—C5—C6	178.97 (12)	C7—C8—C9—C10	179.26 (14)
C3—C4—C5—C6	−1.8 (2)	C8—C9—C10—C11	−178.38 (15)
O2—C4—C5—C12	−2.5 (2)	C4—C5—C12—O3	2.4 (2)
C3—C4—C5—C12	176.76 (13)	C6—C5—C12—O3	−179.11 (13)
C2—C1—C6—C5	−0.3 (2)	C4—C5—C12—O4	−176.99 (12)
C2—C1—C6—C7	179.01 (13)	C6—C5—C12—O4	1.5 (2)
C4—C5—C6—C1	2.0 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	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+1/2, y+1/2, −z+1/2; (ii) −x, −y−1, −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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research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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

1. Chemical context

2. Structural commentary

3. Supra­molecular features

4. Crystallization

5. Refinement

Supporting information

Acknowledgements

References

research communications

3. Supramolecular features