Redetermined structure of 4-(benz­yloxy)benzoic acid

Qiuyi Song; Sihui Long

doi:10.1107/S2414314624007521

. 2024 Aug 6;9(Pt 8):x240752. doi: 10.1107/S2414314624007521

Redetermined structure of 4-(benzyloxy)benzoic acid

Qiuyi Song ^a, Sihui Long ^b,^*

Editor: W T A Harrison^c

PMCID: PMC11375600 PMID: 39247081

The molecules of the title compound form acid–acid homodimers in the crystal structure.

Keywords: synthon, hydrogen bond, acid-acid dimer, crystal structure

Abstract

In the title compound, C₁₄H₁₄O₃, the dihedral angle between the aromatic rings is 39.76 (9)°. In the crystal, the molecules associate to form centrosymmetric acid–acid dimers linked by pairwise O—H⋯O hydrogen bonds. The precision of the geometric parameters in the present single-crystal study is about an order of magnitude better than the previous powder diffraction study [Chattopadhyay et al. (2013 ▸). CrystEngComm, 15, 1077–1085].

Structure description

Non-steroidal anti-inflammatory drugs (NSAIDs) constitute approximately 5–10% of all prescribed medicines worldwide as antipyretic, anti-inflammatory and analgesic agents (Sohail et al., 2023 ▸). Moreover, they are found to have a protective role against various critical diseases, such as cancer and cardiovascular diseases (Prasher & Sharma, 2021 ▸). It is estimated that 30 million individuals use NSAIDs daily (Bhala et al., 2013 ▸).

As part of our studies in this area, the title compound (Fig. 1 ▸) was synthesized by a two-step reaction. The C1–C6 and C9–C14 aromatic rings subtend a dihedral angle of 39.76 (9)° and the linking C4—O3—C8—C9 bond has an anti conformation [torsion angle = −171.59 (12)°]. The short C4—O3 bond length of 1.3601 (16) Å indicates some conjugation of the O atom lone pair with the adjacent aromatic ring.

The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level.

In the extended structure, molecules pair up to form carboxylic acid–carboxylic acid hydrogen-bonded dimers (Table 1 ▸, Fig. 2 ▸). The crystal structure of the title compound was also solved from X-ray powder diffraction data (Chattopadhyay et al., 2013 ▸) with corresponding hydrogen-bond parameters of 1.94 Å and 176°, respectively, which deviate from those obtained in this study from single-crystal X-ray diffraction.

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯O2ⁱ	0.82	1.81	2.6213 (15)	169

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Symmetry code: (i) Inline graphic .

Packing of the molecules in the title compound (for clarity, H atoms not involved in hydrogen bonding are omitted).

Synthesis and crystallization

The title compound was prepared by a two-step reaction (Fig. 3 ▸). The product was purified by column chromatography. Single crystals were obtained by slowly evaporating an ethanol solution of the title compound.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸.

Table 2. Experimental details.

Crystal data
Chemical formula	C₁₄H₁₂O₃
M _r	228.24
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	305
a, b, c (Å)	10.0564 (5), 3.9985 (2), 28.2235 (14)
β (°)	97.744 (5)
V (Å³)	1124.54 (10)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.10
Crystal size (mm)	0.16 × 0.15 × 0.13

Data collection
Diffractometer	XtaLAB Synergy R, DW system, HyPix
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2022 ▸)
T_min, T_max	0.875, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	10523, 2793, 1996
R _int	0.019
(sin θ/λ)_max (Å⁻¹)	0.721

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.044, 0.135, 1.08
No. of reflections	2793
No. of parameters	156
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.26, −0.19

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Computer programs: CrysAlis PRO (Rigaku OD, 2022 ▸), SHELXT2018/3 (Sheldrick, 2015b ▸), SHELXL2018/3 (Sheldrick, 2015b ▸) and OLEX2 (Dolomanov et al., 2009 ▸).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2414314624007521/hb4473sup1.cif

x-09-x240752-sup1.cif^{(347.2KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2414314624007521/hb4473Isup2.hkl

x-09-x240752-Isup2.hkl^{(223.5KB, hkl)}

x-09-x240752-Isup3.cml^{(4.4KB, cml)}

Supporting information file. DOI: 10.1107/S2414314624007521/hb4473Isup3.cml

CCDC reference: 2374704

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

Acknowledgments

QS thanks the Graduate Innovation Fund of WIT for financial support.

full crystallographic data

4-(Benzyloxy)benzoic acid. Crystal data

C₁₄H₁₂O₃	F(000) = 480
M_r = 228.24	D_x = 1.348 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
a = 10.0564 (5) Å	Cell parameters from 5298 reflections
b = 3.9985 (2) Å	θ = 2.1–29.8°
c = 28.2235 (14) Å	µ = 0.10 mm⁻¹
β = 97.744 (5)°	T = 305 K
V = 1124.54 (10) Å³	Block, clear light colourless
Z = 4	0.16 × 0.15 × 0.13 mm

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4-(Benzyloxy)benzoic acid. Data collection

XtaLAB Synergy R, DW system, HyPix diffractometer	2793 independent reflections
Radiation source: Rotating-anode X-ray tube, Rigaku (Mo) X-ray Source	1996 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.019
Detector resolution: 10.0000 pixels mm^-1	θ_max = 30.8°, θ_min = 2.1°
ω scans	h = −12→13
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2022)	k = −4→5
T_min = 0.875, T_max = 1.000	l = −29→37
10523 measured reflections

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4-(Benzyloxy)benzoic acid. Refinement

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.044	w = 1/[σ²(F_o²) + (0.0641P)² + 0.1717P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.135	(Δ/σ)_max < 0.001
S = 1.08	Δρ_max = 0.26 e Å⁻³
2793 reflections	Δρ_min = −0.19 e Å⁻³
156 parameters	Extinction correction: SHELXL2018/3 (Sheldrick, 2015b), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.008 (2)

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4-(Benzyloxy)benzoic acid. Special details

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.

Refinement. The positions of the H atom attached to O1 was obtained from a difference Fourier map. Other H atoms were positioned geometrically with C—H = 0.93 Å and constrained to ride on their parent atoms with U_iso(H) = 1.2U_eq(C,O).

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4-(Benzyloxy)benzoic acid. Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²)

	x	y	z	U_iso*/U_eq
O3	0.35692 (9)	0.6152 (3)	0.36054 (4)	0.0557 (3)
O2	0.94382 (10)	0.2255 (4)	0.45018 (4)	0.0666 (4)
O1	0.83138 (10)	0.0288 (4)	0.50696 (4)	0.0658 (4)
H1	0.906153	−0.043118	0.517133	0.099*
C4	0.46870 (13)	0.5035 (4)	0.38859 (5)	0.0444 (3)
C5	0.58913 (14)	0.5572 (4)	0.37085 (5)	0.0503 (4)
H5	0.589311	0.663292	0.341539	0.060*
C6	0.70792 (13)	0.4545 (4)	0.39638 (5)	0.0491 (4)
H6	0.788198	0.490876	0.384244	0.059*
C1	0.70890 (12)	0.2960 (4)	0.44041 (4)	0.0431 (3)
C2	0.58902 (13)	0.2464 (4)	0.45795 (5)	0.0495 (4)
H2	0.589103	0.142972	0.487473	0.059*
C3	0.46833 (14)	0.3477 (4)	0.43243 (5)	0.0505 (4)
H3	0.388052	0.311700	0.444589	0.061*
C8	0.22907 (13)	0.5294 (4)	0.37376 (5)	0.0526 (4)
H8A	0.216021	0.642645	0.403176	0.063*
H8B	0.224207	0.290205	0.378971	0.063*
C9	0.12226 (13)	0.6340 (3)	0.33413 (5)	0.0452 (3)
C10	0.13472 (15)	0.5661 (4)	0.28683 (5)	0.0548 (4)
H10	0.211545	0.460996	0.279204	0.066*
C11	0.03322 (16)	0.6542 (4)	0.25081 (6)	0.0616 (4)
H11	0.042281	0.608856	0.219082	0.074*
C12	−0.08060 (15)	0.8081 (4)	0.26183 (6)	0.0625 (4)
H12	−0.148833	0.865897	0.237618	0.075*
C13	−0.09369 (15)	0.8766 (4)	0.30845 (6)	0.0623 (4)
H13	−0.170991	0.980303	0.315929	0.075*
C14	0.00810 (14)	0.7917 (4)	0.34459 (6)	0.0536 (4)
H14	−0.000845	0.841711	0.376181	0.064*
C7	0.83567 (13)	0.1772 (4)	0.46735 (5)	0.0467 (3)

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4-(Benzyloxy)benzoic acid. Atomic displacement parameters (Å²)

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O3	0.0376 (5)	0.0723 (7)	0.0548 (6)	−0.0030 (5)	−0.0018 (4)	0.0171 (5)
O2	0.0403 (5)	0.1045 (10)	0.0549 (6)	0.0051 (6)	0.0064 (4)	0.0152 (6)
O1	0.0449 (6)	0.0978 (9)	0.0527 (6)	0.0062 (6)	0.0000 (5)	0.0210 (6)
C4	0.0394 (7)	0.0492 (8)	0.0425 (7)	−0.0025 (6)	−0.0015 (5)	0.0019 (6)
C5	0.0461 (7)	0.0633 (9)	0.0407 (7)	−0.0034 (6)	0.0029 (6)	0.0094 (6)
C6	0.0378 (7)	0.0648 (9)	0.0447 (7)	−0.0040 (6)	0.0056 (5)	0.0046 (6)
C1	0.0390 (7)	0.0499 (8)	0.0392 (6)	−0.0014 (5)	0.0011 (5)	−0.0005 (5)
C2	0.0434 (7)	0.0629 (9)	0.0417 (7)	−0.0008 (6)	0.0038 (5)	0.0089 (6)
C3	0.0378 (7)	0.0644 (10)	0.0492 (8)	−0.0020 (6)	0.0058 (5)	0.0083 (7)
C8	0.0405 (7)	0.0618 (9)	0.0546 (8)	−0.0032 (6)	0.0025 (6)	0.0103 (7)
C9	0.0374 (6)	0.0455 (8)	0.0515 (8)	−0.0053 (5)	0.0019 (5)	0.0046 (6)
C10	0.0462 (8)	0.0608 (10)	0.0573 (8)	0.0017 (7)	0.0068 (6)	−0.0025 (7)
C11	0.0607 (9)	0.0722 (11)	0.0497 (8)	−0.0119 (8)	−0.0004 (7)	0.0001 (7)
C12	0.0449 (8)	0.0691 (11)	0.0689 (10)	−0.0100 (7)	−0.0094 (7)	0.0173 (8)
C13	0.0396 (7)	0.0666 (11)	0.0803 (11)	0.0039 (7)	0.0063 (7)	0.0117 (8)
C14	0.0438 (7)	0.0609 (9)	0.0568 (8)	−0.0024 (7)	0.0090 (6)	0.0022 (7)
C7	0.0406 (7)	0.0584 (9)	0.0403 (7)	−0.0004 (6)	0.0022 (5)	−0.0007 (6)

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4-(Benzyloxy)benzoic acid. Geometric parameters (Å, º)

O3—C4	1.3601 (16)	C3—H3	0.9300
O3—C8	1.4279 (17)	C8—H8A	0.9700
O2—C7	1.2636 (17)	C8—H8B	0.9700
O1—H1	0.8200	C8—C9	1.5019 (19)
O1—C7	1.2716 (17)	C9—C10	1.384 (2)
C4—C5	1.3881 (19)	C9—C14	1.376 (2)
C4—C3	1.3857 (19)	C10—H10	0.9300
C5—H5	0.9300	C10—C11	1.386 (2)
C5—C6	1.3721 (19)	C11—H11	0.9300
C6—H6	0.9300	C11—C12	1.372 (2)
C6—C1	1.3937 (19)	C12—H12	0.9300
C1—C2	1.3780 (18)	C12—C13	1.368 (2)
C1—C7	1.4723 (18)	C13—H13	0.9300
C2—H2	0.9300	C13—C14	1.386 (2)
C2—C3	1.3858 (19)	C14—H14	0.9300

C4—O3—C8	118.15 (11)	C9—C8—H8A	110.0
C7—O1—H1	109.5	C9—C8—H8B	110.0
O3—C4—C5	115.61 (12)	C10—C9—C8	121.00 (13)
O3—C4—C3	124.46 (12)	C14—C9—C8	120.09 (13)
C3—C4—C5	119.93 (12)	C14—C9—C10	118.89 (13)
C4—C5—H5	119.9	C9—C10—H10	119.9
C6—C5—C4	120.30 (12)	C9—C10—C11	120.29 (14)
C6—C5—H5	119.9	C11—C10—H10	119.9
C5—C6—H6	119.8	C10—C11—H11	119.9
C5—C6—C1	120.36 (12)	C12—C11—C10	120.15 (15)
C1—C6—H6	119.8	C12—C11—H11	119.9
C6—C1—C7	120.58 (12)	C11—C12—H12	120.0
C2—C1—C6	118.97 (12)	C13—C12—C11	119.97 (14)
C2—C1—C7	120.44 (12)	C13—C12—H12	120.0
C1—C2—H2	119.4	C12—C13—H13	120.0
C1—C2—C3	121.23 (13)	C12—C13—C14	120.10 (15)
C3—C2—H2	119.4	C14—C13—H13	120.0
C4—C3—C2	119.21 (13)	C9—C14—C13	120.60 (14)
C4—C3—H3	120.4	C9—C14—H14	119.7
C2—C3—H3	120.4	C13—C14—H14	119.7
O3—C8—H8A	110.0	O2—C7—O1	122.78 (12)
O3—C8—H8B	110.0	O2—C7—C1	118.87 (12)
O3—C8—C9	108.51 (11)	O1—C7—C1	118.36 (12)
H8A—C8—H8B	108.4

O3—C4—C5—C6	179.92 (14)	C2—C1—C7—O1	0.0 (2)
O3—C4—C3—C2	−179.61 (14)	C3—C4—C5—C6	0.5 (2)
O3—C8—C9—C10	45.48 (19)	C8—O3—C4—C5	172.07 (13)
O3—C8—C9—C14	−136.32 (14)	C8—O3—C4—C3	−8.5 (2)
C4—O3—C8—C9	−171.59 (12)	C8—C9—C10—C11	177.81 (14)
C4—C5—C6—C1	−0.2 (2)	C8—C9—C14—C13	−177.25 (14)
C5—C4—C3—C2	−0.2 (2)	C9—C10—C11—C12	−0.3 (3)
C5—C6—C1—C2	−0.4 (2)	C10—C9—C14—C13	1.0 (2)
C5—C6—C1—C7	178.37 (14)	C10—C11—C12—C13	0.4 (3)
C6—C1—C2—C3	0.7 (2)	C11—C12—C13—C14	0.2 (3)
C6—C1—C7—O2	0.9 (2)	C12—C13—C14—C9	−0.9 (2)
C6—C1—C7—O1	−178.79 (15)	C14—C9—C10—C11	−0.4 (2)
C1—C2—C3—C4	−0.4 (2)	C7—C1—C2—C3	−178.11 (14)
C2—C1—C7—O2	179.73 (14)

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4-(Benzyloxy)benzoic acid. Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O2ⁱ	0.82	1.81	2.6213 (15)	169

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Symmetry code: (i) −x+2, −y, −z+1.

References

Chattopadhyay, B., Das, U., Mukherjee, M. & Mukherjee, A. K. (2013). CrystEngComm, 15, 1077–1085.
Bhala, N., Emberson, J., Merhi, A., Abramson, S., Arber, N., Baron, J. A., Bombardier, C., Cannon, C., Farkouh, M. E., FitzGerald, G. A., Goss, P., Halls, H., Hawk, E., Hawkey, C., Hennekens, C., Hochberg, M., Holland, L. E., Kearney, P. M., Laine, L., Lanas, A., Lance, P., Laupacis, A., Oates, J., Patrono, C., Schnitzer, T. J., Solomon, S., Tugwell, P., Wilson, K., Wittes, J. & Baigent, C. (2013). Lancet, 382, 769–779.
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst.42, 339–341.
Prasher, P. & Sharma, M. (2021). Drug Dev. Res.82, 945–958. [DOI] [PubMed]
Rigaku OD (2022). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.
Sohail, R., Mathew, M., Patel, K. K., Reddy, S. A., Haider, Z., Naria, M., Habib, A., Abdin, Z. U., Chaudhry, W. R. & Akbar, A. (2023). Cureus, 15, e37080. [DOI] [PMC free article] [PubMed]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2414314624007521/hb4473sup1.cif

x-09-x240752-sup1.cif^{(347.2KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2414314624007521/hb4473Isup2.hkl

x-09-x240752-Isup2.hkl^{(223.5KB, hkl)}

x-09-x240752-Isup3.cml^{(4.4KB, cml)}

Supporting information file. DOI: 10.1107/S2414314624007521/hb4473Isup3.cml

CCDC reference: 2374704

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

[bb1] Chattopadhyay, B., Das, U., Mukherjee, M. & Mukherjee, A. K. (2013). CrystEngComm, 15, 1077–1085.

[bb2] Bhala, N., Emberson, J., Merhi, A., Abramson, S., Arber, N., Baron, J. A., Bombardier, C., Cannon, C., Farkouh, M. E., FitzGerald, G. A., Goss, P., Halls, H., Hawk, E., Hawkey, C., Hennekens, C., Hochberg, M., Holland, L. E., Kearney, P. M., Laine, L., Lanas, A., Lance, P., Laupacis, A., Oates, J., Patrono, C., Schnitzer, T. J., Solomon, S., Tugwell, P., Wilson, K., Wittes, J. & Baigent, C. (2013). Lancet, 382, 769–779.

[bb3] Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst.42, 339–341.

[bb4] Prasher, P. & Sharma, M. (2021). Drug Dev. Res.82, 945–958. [DOI] [PubMed]

[bb8] Rigaku OD (2022). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.

[bb5] Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.

[bb6] Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.

[bb7] Sohail, R., Mathew, M., Patel, K. K., Reddy, S. A., Haider, Z., Naria, M., Habib, A., Abdin, Z. U., Chaudhry, W. R. & Akbar, A. (2023). Cureus, 15, e37080. [DOI] [PMC free article] [PubMed]

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Redetermined structure of 4-(benzyloxy)benzoic acid

Qiuyi Song

Sihui Long

Roles

Abstract

Structure description