Crystal structure and Hirshfeld surface analysis of a third polymorph of 2,6-di­meth­oxy­benzoic acid

A third monoclinic polymorph of 2,6-di­meth­oxy­bnzoic acid is reported. The acidic O—H bond of the carboxyl group adopts a synplanar conformation.

Abstract

A third crystalline form of the title compound, C₉H₁₀O₄, crystallizing in the centrosymmetric monoclinic space group P2₁/c, has been identified during screening for co-crystals. The asymmetric unit comprises a non-planar independent mol­ecule with a synplanar conformation of the OH group. The sterically bulky o-meth­oxy substituents force the carb­oxy group to be twisted away from the plane of the benzene ring by 74.10 (6)°. The carb­oxy group exhibits the acidic H atom disordered over two sites between two O atoms. A similar situation has been found for the second tetra­gonal polymorph reported [Portalone (2011 ▸). Acta Cryst. E67, o3394–o3395], in which mol­ecules with the OH group in a synplanar conformation form dimeric units via strong O—H⋯O hydrogen bonds. In contrast, in the first ortho­rhom­bic form reported [Swaminathan et al. (1976 ▸). Acta Cryst. B32, 1897–1900; Bryan & White (1982 ▸). Acta Cryst. B38, 1014–1016; Portalone (2009 ▸). Acta Cryst. E65, o327–o328], the mol­ecular components do not form conventional dimeric units, as an anti­planar conformation adopted by the OH group favors the association of mol­ecules in chains stabilized by linear O—H⋯O hydrogen bonds.

Chemical context  

Until now, two polymorphs are known for 2,6-di­meth­oxy­benzoic acid. Polymorph (Iα) crystallizes in the ortho­rhom­bic space group P2₁2₁2₁ with one mol­ecule in the asymmetric unit (Swaminathan et al., 1976 ▸; Bryan & White, 1982 ▸; Portalone, 2009 ▸). As a result of the anti­planar conformation adopted by the OH group, the mol­ecular components are associated in the crystal in chains stabilized by linear O—H⋯O hydrogen bonds. Polymorph (Iβ) crystallizes in the tetra­gonal space group P4₁2₁2 with one mol­ecule in the asymmetric unit (Portalone, 2011 ▸). In the crystal of the second polymorph, the synplanar conformation of the OH group favours the formation of dimers through O—H⋯O hydrogen bonds. In this article, it is reported the crystal structure of a third polymorph, (Iγ), of 2,6-di­meth­oxy­benzoic acid produced unexpectedly during an attempt to synthesize co-crystals of 5-fluoro­uracil with the title compound.

Structural commentary  

The title compound (Iγ) crystallizes in the monoclinic centrosymmetric space group P2₁/c, and the asymmetric unit comprises a non-planar independent mol­ecule. The carb­oxy group is twisted away from the plane of the benzene ring by 74.10 (6)° because of a significant steric hindrance of the two o-meth­oxy substituents (Fig. 1 ▸). The above angle between the planes is comparable with that found for the ortho­rhom­bic form, 56.12 (9)°, and for the tetra­gonal form, 65.72 (15)°. The carb­oxy group, in which OH adopts a synplanar conformation similar to that observed for the tetra­gonal form, exhibits the carb­oxy H atom disordered over two sites between two O atoms. The pattern of bond lengths and bond angles of the phenyl ring is consistent with that reported in the structure determination of the two previously determined polymorphs, and a comparison of the present results with those obtained for similar benzene derivatives (Colapietro et al., 1984 ▸; Irrera et al., 2012 ▸; Portalone, 2012 ▸) shows no appreciable effects of the crystal environment on the ring deformation induced by substituents.

Figure 1.

The mol­ecular structure of (Iγ), showing the atom-labeling scheme. Displacement ellipsoids are at the 50% probability level.

Supra­molecular features  

Analysis of the crystal packing of (Iγ), (Fig. 2 ▸), shows that the mol­ecular components form the conventional dimeric units observed in benzoic acids (Leiserowitz, 1976 ▸; Kanters et al., 1991 ▸; Moorthy et al., 2002 ▸). Indeed, the crystal structure is stabilized by strong inter­molecular O—H⋯O hydrogen bonds, which link inversion-related mol­ecules into homodimers (Table 1 ▸). These homodimers are then joined by weak C—H⋯O inter­molecular inter­actions of graph-set motif (6) between the meth­oxy and the carb­oxy groups of adjacent mol­ecules to form a two-dimensional network parallel to the bc plane.

Figure 2.

Crystal packing diagram for (Iγ) viewed approximately down the a axis. All atoms are shown as small spheres of arbitrary radii. Hydrogen bonding is indicated by red dashed lines.

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯O2i	0.86 (6)	1.79 (6)	2.6411 (15)	174 (4)
O2—H2⋯O1i	0.81 (6)	1.84 (6)	2.6411 (15)	167 (5)
C9—H9A⋯O2ii	0.97	2.60	3.571 (3)	178

Symmetry codes: (i) ; (ii) .

The Hirshfeld surface analysis (Spackman & Jayatilaka, 2009 ▸) was carried out using CrystalExplorer (Turner et al., 2017 ▸). The surface enables the visualization of inter­molecular contacts over the surface by different colors and color intensity, and shorter and longer contacts are indicated as red and blue spots, respectively. In Fig. 3 ▸ are shown the 3D Hirshfeld surface, modeled by choosing one of the two equally disordered components and mapped over d _norm, and the two-dimensional fingerprint plots, which give the contribution of the inter­atomic contacts to the Hirshfeld surface. The most prominent inter­actions, due to strong O—H⋯O hydrogen bonds, are shown by large and deep red spots on the surface. Small red spots on the surface indicate the areas where close-contact inter­actions due to weak C—H⋯O hydrogen bonds take place. The H⋯H contacts, representing van der Waals inter­actions, and the O⋯H/H⋯O contacts, representing inter­molecular hydrogen bonds, are the most populated contacts and contribute 39.2 and 39.1% of the total inter­molecular contacts, respectively. Other important contacts, such as C⋯H/H⋯C (19.1%), also supplement the overall crystal packing. The contributions of the O⋯C/C⋯O (2.5%) contacts are less significant.

Figure 3.

(a) A view of the three-dimensional Hirshfeld surface of the title compound mapped over d _norm with a fixed color scale of −0.742 (red) to 1.283 (blue) a.u. (b), (c), (d), (e) and (f): decomposed two-dimensional fingerprint plots for the title compound showing various close contacts and their proportional contributions.

Database survey  

A search of crystal structure of 2,6-dimeth­oxy benzoic acid alone in the Cambridge Crystallographic Database (CSD version 5.41, May 2020 update; Groom et al., 2016 ▸) yielded four hits as crystalline polymorphs. Three were for the ortho­rhom­bic polymorph: DMOXBA (Swaminathan et al., 1976 ▸), DMOXBA01 (Bryan & White, 1982 ▸) and DMOXBA02 (Portalone, 2009 ▸); the fourth one was for the tetra­gonal polymorph: DMOXBA03 (Portalone, 2011 ▸).

Synthesis and crystallization  

Polymorph (Iγ) was formed from an unsuccessful co-crystallization between 2,6-di­meth­oxy­benzoic acid and 5-fluoro­uracil. Colorless plate-like crystals were formed by the slow evaporation of an aqueous solution of 2,6-di­meth­oxy­benzoic acid (1 mmol, Sigma Aldrich at 99% purity) and 5-fluoro­uracil (1 mmol, Sigma Aldrich at 99% purity) in a 1:1 molar ratio.

Refinement  

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. All H atoms were identified in difference-Fourier maps, but in the refinement all C-bound H atoms were placed in calculated positions, with C—H = 0.97 Å, and refined as riding on their carrier atoms, with U _iso(H) = 1.2U _eq(C_phen­yl) or 1.5U _eq(C_meth­yl). A rotating group model was applied to the methyl groups. The remaining two halves of the disordered O-bound H atom, H1 and H2, were refined freely and their U _iso values were kept equal to 1.2U _eq(O). Site-occupation factors of H1 and H2 refined to 0.53 (3) and 0.47 (3), respectively.

Table 2. Experimental details.

Crystal data
Chemical formula	C9H10O4
M r	182.17
Crystal system, space group	Monoclinic, P21/c
Temperature (K)	298
a, b, c (Å)	7.7574 (10), 8.4763 (10), 14.3322 (19)
β (°)	97.526 (12)
V (Å3)	934.3 (2)
Z	4
Radiation type	Mo Kα
μ (mm−1)	0.10
Crystal size (mm)	0.20 × 0.14 × 0.11
Data collection
Diffractometer	Oxford Diffraction Xcalibur S CCD
Absorption correction	Multi-scan (CrysAlis RED; Rigaku OD, 2018 ▸)
T min, T max	0.970, 0.999
No. of measured, independent and observed [I > 2σ(I)] reflections	9067, 2708, 1420
R int	0.040
(sin θ/λ)max (Å−1)	0.704
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.049, 0.132, 1.02
No. of reflections	2708
No. of parameters	134
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.14, −0.12

Computer programs: CrysAlis PRO (Rigaku OD, 2018 ▸), SIR2004 (Burla et al., 2005 ▸), SHELXL2014/7 (Sheldrick, 2015 ▸) and WinGX (Farrugia, 2012 ▸).

Supplementary Material

CCDC reference: 2042162

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

supplementary crystallographic information

Crystal data

C9H10O4	F(000) = 384
Mr = 182.17	Dx = 1.295 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.710689 Å
a = 7.7574 (10) Å	Cell parameters from 1806 reflections
b = 8.4763 (10) Å	θ = 2.9–32.6°
c = 14.3322 (19) Å	µ = 0.10 mm−1
β = 97.526 (12)°	T = 298 K
V = 934.3 (2) Å3	Tablets, colourless
Z = 4	0.20 × 0.14 × 0.11 mm

Data collection

Oxford Diffraction Xcalibur S CCD diffractometer	2708 independent reflections
Radiation source: Enhance (Mo) X-ray source	1420 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.040
Detector resolution: 16.0696 pixels mm-1	θmax = 30.0°, θmin = 2.9°
ω and φ scans	h = −10→10
Absorption correction: multi-scan (CrysAlis RED; Rigaku OD, 2018)	k = −11→6
Tmin = 0.970, Tmax = 0.999	l = −19→20
9067 measured reflections

Refinement

Refinement on F2	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.049	w = 1/[σ2(Fo2) + (0.0439P)2 + 0.0492P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.132	(Δ/σ)max < 0.001
S = 1.02	Δρmax = 0.14 e Å−3
2708 reflections	Δρmin = −0.12 e Å−3
134 parameters	Extinction correction: SHELXL-2014/7 (Sheldrick 2015\bbr000), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraints	Extinction coefficient: 0.031 (4)

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
O1	0.50254 (16)	0.32576 (15)	0.56267 (9)	0.0726 (4)
H1	0.446 (6)	0.372 (5)	0.515 (3)	0.087*	0.53 (3)
O2	0.68711 (16)	0.52450 (15)	0.57631 (9)	0.0776 (5)
H2	0.643 (7)	0.571 (6)	0.530 (4)	0.093*	0.47 (3)
O3	0.94633 (16)	0.24939 (16)	0.59823 (10)	0.0827 (4)
O4	0.50328 (18)	0.39851 (17)	0.76761 (9)	0.0900 (5)
C1	0.73003 (19)	0.31878 (17)	0.68819 (11)	0.0531 (4)
C2	0.8886 (2)	0.24603 (19)	0.68370 (13)	0.0622 (5)
C3	0.9743 (2)	0.1717 (2)	0.76309 (15)	0.0767 (6)
H3	1.0852	0.1199	0.7610	0.092*
C4	0.8991 (3)	0.1731 (2)	0.84415 (15)	0.0836 (7)
H4	0.9582	0.1201	0.8992	0.100*
C5	0.7430 (3)	0.2467 (2)	0.85095 (13)	0.0782 (6)
H5	0.6940	0.2474	0.9099	0.094*
C6	0.6574 (2)	0.3199 (2)	0.77134 (12)	0.0648 (5)
C7	0.63417 (19)	0.39559 (18)	0.60344 (10)	0.0508 (4)
C8	1.1123 (3)	0.1829 (4)	0.5897 (2)	0.1261 (10)
H8A	1.2012	0.2385	0.6310	0.158 (12)*
H8B	1.1358	0.1925	0.5251	0.152 (12)*
H8C	1.1129	0.0723	0.6072	0.169 (13)*
C9	0.4198 (3)	0.4098 (3)	0.84841 (17)	0.0986 (7)
H9A	0.3944	0.3048	0.8698	0.139 (10)*
H9B	0.3122	0.4684	0.8337	0.129 (9)*
H9C	0.4950	0.4641	0.8976	0.155 (12)*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O1	0.0660 (8)	0.0702 (8)	0.0718 (8)	−0.0169 (6)	−0.0278 (6)	0.0167 (6)
O2	0.0747 (8)	0.0651 (8)	0.0823 (9)	−0.0180 (6)	−0.0302 (7)	0.0257 (7)
O3	0.0585 (8)	0.1008 (10)	0.0873 (10)	0.0180 (7)	0.0041 (6)	0.0170 (8)
O4	0.0984 (10)	0.1059 (11)	0.0659 (9)	0.0408 (8)	0.0118 (7)	0.0165 (7)
C1	0.0513 (8)	0.0503 (8)	0.0525 (9)	0.0003 (7)	−0.0128 (7)	0.0062 (7)
C2	0.0512 (9)	0.0611 (10)	0.0693 (12)	−0.0009 (7)	−0.0108 (8)	0.0098 (8)
C3	0.0579 (10)	0.0739 (12)	0.0904 (14)	0.0082 (9)	−0.0199 (10)	0.0192 (10)
C4	0.0835 (14)	0.0788 (13)	0.0775 (14)	0.0018 (11)	−0.0309 (11)	0.0234 (10)
C5	0.0925 (15)	0.0788 (12)	0.0580 (11)	0.0040 (11)	−0.0103 (9)	0.0152 (9)
C6	0.0712 (11)	0.0584 (10)	0.0599 (11)	0.0086 (8)	−0.0104 (9)	0.0068 (8)
C7	0.0461 (8)	0.0509 (8)	0.0522 (9)	0.0012 (7)	−0.0057 (6)	0.0047 (7)
C8	0.0704 (16)	0.173 (3)	0.138 (3)	0.0443 (17)	0.0250 (17)	0.037 (2)
C9	0.1151 (19)	0.0953 (17)	0.0891 (16)	0.0249 (15)	0.0273 (15)	0.0135 (14)

Geometric parameters (Å, º)

O1—C7	1.2563 (17)	C3—C4	1.367 (3)
O1—H1	0.86 (6)	C3—H3	0.9700
O2—C7	1.2472 (18)	C4—C5	1.377 (3)
O2—H2	0.81 (6)	C4—H4	0.9700
O3—C2	1.359 (2)	C5—C6	1.389 (2)
O3—C8	1.425 (2)	C5—H5	0.9700
O4—C6	1.363 (2)	C8—H8A	0.9701
O4—C9	1.402 (2)	C8—H8B	0.9701
C1—C6	1.383 (2)	C8—H8C	0.9701
C1—C2	1.385 (2)	C9—H9A	0.9701
C1—C7	1.4885 (19)	C9—H9B	0.9701
C2—C3	1.391 (2)	C9—H9C	0.9701
C7—O1—H1	117 (3)	O4—C6—C1	115.07 (14)
C7—O2—H2	124 (3)	O4—C6—C5	124.95 (19)
C2—O3—C8	118.50 (17)	C1—C6—C5	119.97 (17)
C6—O4—C9	119.91 (16)	O2—C7—O1	123.27 (13)
C6—C1—C2	120.51 (14)	O2—C7—C1	119.20 (13)
C6—C1—C7	118.92 (14)	O1—C7—C1	117.53 (14)
C2—C1—C7	120.57 (16)	O3—C8—H8A	109.5
O3—C2—C1	115.62 (14)	O3—C8—H8B	109.5
O3—C2—C3	124.61 (17)	H8A—C8—H8B	109.5
C1—C2—C3	119.74 (18)	O3—C8—H8C	109.5
C4—C3—C2	118.64 (18)	H8A—C8—H8C	109.5
C4—C3—H3	120.7	H8B—C8—H8C	109.5
C2—C3—H3	120.7	O4—C9—H9A	109.5
C3—C4—C5	122.81 (16)	O4—C9—H9B	109.5
C3—C4—H4	118.6	H9A—C9—H9B	109.5
C5—C4—H4	118.6	O4—C9—H9C	109.5
C4—C5—C6	118.33 (19)	H9A—C9—H9C	109.5
C4—C5—H5	120.8	H9B—C9—H9C	109.5
C6—C5—H5	120.8
C8—O3—C2—C1	177.2 (2)	C9—O4—C6—C5	0.1 (3)
C8—O3—C2—C3	−4.9 (3)	C2—C1—C6—O4	178.43 (14)
C6—C1—C2—O3	178.84 (15)	C7—C1—C6—O4	−2.2 (2)
C7—C1—C2—O3	−0.5 (2)	C2—C1—C6—C5	−0.5 (3)
C6—C1—C2—C3	0.9 (2)	C7—C1—C6—C5	178.92 (15)
C7—C1—C2—C3	−178.51 (14)	C4—C5—C6—O4	−179.32 (17)
O3—C2—C3—C4	−178.01 (17)	C4—C5—C6—C1	−0.5 (3)
C1—C2—C3—C4	−0.2 (3)	C6—C1—C7—O2	106.30 (19)
C2—C3—C4—C5	−0.8 (3)	C2—C1—C7—O2	−74.3 (2)
C3—C4—C5—C6	1.2 (3)	C6—C1—C7—O1	−73.7 (2)
C9—O4—C6—C1	−178.74 (18)	C2—C1—C7—O1	105.66 (18)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O2i	0.86 (6)	1.79 (6)	2.6411 (15)	174 (4)
O2—H2···O1i	0.81 (6)	1.84 (6)	2.6411 (15)	167 (5)
C9—H9A···O2ii	0.97	2.60	3.571 (3)	178

Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x+1, y−1/2, −z+3/2.