Crystal structure of 3-(2,5-di­meth­oxy­phen­yl)propionic acid

In the crystal of the title compound, C₁₁H₁₄O₄, the aromatic ring is almost coplanar with the 2-position meth­oxy group with which it subtends a dihedral of 0.54 (2)°, while the 5-position meth­oxy group makes a corresponding dihedral angle of just 5.30 (2)°. The angle between the mean planes of the aromatic ring and the propionic acid group is 78.56 (2)°. The fully extended propionic side chain is in a trans configuration with a C—C—C—C torsion angle of −172.25 (7)°. In the crystal, hydrogen bonding is limited to dimer formation via R₂²(8) rings. The hydrogen-bonded dimers are stacked along the b axis. The average planes of the two benzene rings in a dimer are parallel to each other, but at an offset of 4.31 (2) Å. Within neighbouring dimers along the [101] direction, the average mol­ecular benzene planes are almost perpendicular to each other, with a dihedral angle of 85.33 (2)°.

Key indicators

• Single-crystal X-ray study
• T = 100 K
• Mean [sigma](C-C) = 0.001 Å
• R factor = 0.036
• wR factor = 0.107
• Data-to-parameter ratio = 22.7

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT094_ALERT_2_C Ratio of Maximum / Minimum Residual Density ....       2.44 Report
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.600         17 Report
PLAT913_ALERT_3_C Missing # of Very Strong Reflections in FCF ....          3 Note

Alert level G
PLAT912_ALERT_4_G Missing # of FCF Reflections Above STh/L=  0.600        215 Note

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   3 ALERT level C = Check. Ensure it is not caused by an omission or oversight
   1 ALERT level G = General information/check it is not something unexpected

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

---

S1. Structural commentary

The molecule of the title compound exhibits one conformation (Figure 1), unlike other analogous compounds that exhibit two conformations (e.g. 3-phenyl­propionic acid, 3-(3-methyl­phenyl)­propionic acid and 3-(3-meth­oxy­phenyl)­propionic acid) (Das et al., 2012). The aromatic ring of the title compound is almost coplanar with the C10 methoxyl with which it has a dihedral of less than 0.54 (2) ° while the C11 methoxyl has a corresponding dihedral of just 5.30 (2)°. The angle between the mean planes of the aromatic ring and the propionic acid group (C7, C8, C9, O3 and O4) is 78.56 (2) °. The fully extended propionic side chain is in a trans configuration with (C6—C7—C8—C9) torsion angle of -172.25 (2)°. The O4—H4···O3 hydrogen bonding (Table 1) of the COOH functional groups leads to dimer formation via R²₂(8) rings. The hydrogen bonded dimers are stacked along the b axis. The average planes of the two benzene rings in a dimer are parallel to each other, but at an offset of 4.31 (2) Å. Within neighboring dimers along [101] direction, the average molecular benzene planes are almost perpendicular to each other, with an angle of 85.33 (2)°. No other appreciable close contacts were noticed except a very weak C3—H3···π inter­action between adjacent dimers along [101], with a bond length of 3.20 (2) Å.

S2. Synthesis and crystallization

3-(2,5-Di­meth­oxy­phenyl)­propionic acid. - Ethyl 3-(2,5-di­meth­oxy­phenyl)­propionate (3.2 g, 13.4 mmol) in a mixture of aq. NaOH (10 w%, 30 mL) and methanol (8 mL) was heated at reflux for 12h. Then, half. conc. aq. HCl is added to the cooled solution. Thereafter, the mixture is extracted with chloro­form (3 X 15 mL). The organic phase is dried over anhydrous MgSO₄ and concentrated in vacuo. The residue is filtered over a small column of silica gel (di­ethyl­ether–CHCl₃, 1:1, v/v) to give the title compound (2.56 g, 89%) as colorless needles, mp. 339 – 340 K [Lit. mp. 339-340 K (Anliker et al., 1957)]; ν_max (KBr/cm^-1) 3500 – 2050 (bs, OH), 2955, 2835, 1699, 1504, 1449, 1430, 1307, 1281, 1182, 1127, 927, 916, 865, 795, 717, 499; δ_H (400 MHz, CDCl₃) 2.65 (2H, t, ³J = 7.6 Hz), 2.91 (2H, t, ³J = 7.6 Hz), 6.71 (1H, dd, ³J = 8.4 Hz, ⁴J = 3.2 Hz), 6.75 (1H, d, ⁴J = 3.2 Hz), 6.76 (1H, d, ³J = 8.4 Hz), δ_C (67.8 MHz, CDCl₃) 26.0 (CH₂), 33.9 (CH₂), 55.6 (OCH₃), 55.7 (OCH₃), 111.0 (CH), 111.6 (CH), 116.3 (CH), 129.6 (CH), 151.7 (C_quat), 153.3 (C_quat), 179.7 (C_quat, CO).

S3. Refinement

All hydrogen atoms were placed in calculated positions with C—H distances of 0.95- 0.99 Å and refined as riding with U_iso(H) = xU_eq(C), where x = 1.5 for methyl and x = 1.2 for all other H-atoms.

Related literature

For another preparation method of the title compound, see: Anliker et al. (1957). For crystal structures of phenylpropionic acids, see: Das et al. (2012). For the application of the title compound as a starting material for 19-norsteroidal derivatives, see: Anliker et al. (1957); and as a starting material for amidoethylquinones, see: Bremer et al. (2014).

Structure description

The molecule of the title compound exhibits one conformation (Figure 1), unlike other analogous compounds that exhibit two conformations (e.g. 3-phenyl­propionic acid, 3-(3-methyl­phenyl)­propionic acid and 3-(3-meth­oxy­phenyl)­propionic acid) (Das et al., 2012). The aromatic ring of the title compound is almost coplanar with the C10 methoxyl with which it has a dihedral of less than 0.54 (2) ° while the C11 methoxyl has a corresponding dihedral of just 5.30 (2)°. The angle between the mean planes of the aromatic ring and the propionic acid group (C7, C8, C9, O3 and O4) is 78.56 (2) °. The fully extended propionic side chain is in a trans configuration with (C6—C7—C8—C9) torsion angle of -172.25 (2)°. The O4—H4···O3 hydrogen bonding (Table 1) of the COOH functional groups leads to dimer formation via R²₂(8) rings. The hydrogen bonded dimers are stacked along the b axis. The average planes of the two benzene rings in a dimer are parallel to each other, but at an offset of 4.31 (2) Å. Within neighboring dimers along [101] direction, the average molecular benzene planes are almost perpendicular to each other, with an angle of 85.33 (2)°. No other appreciable close contacts were noticed except a very weak C3—H3···π inter­action between adjacent dimers along [101], with a bond length of 3.20 (2) Å.

For another preparation method of the title compound, see: Anliker et al. (1957). For crystal structures of phenylpropionic acids, see: Das et al. (2012). For the application of the title compound as a starting material for 19-norsteroidal derivatives, see: Anliker et al. (1957); and as a starting material for amidoethylquinones, see: Bremer et al. (2014).

Synthesis and crystallization

3-(2,5-Di­meth­oxy­phenyl)­propionic acid. - Ethyl 3-(2,5-di­meth­oxy­phenyl)­propionate (3.2 g, 13.4 mmol) in a mixture of aq. NaOH (10 w%, 30 mL) and methanol (8 mL) was heated at reflux for 12h. Then, half. conc. aq. HCl is added to the cooled solution. Thereafter, the mixture is extracted with chloro­form (3 X 15 mL). The organic phase is dried over anhydrous MgSO₄ and concentrated in vacuo. The residue is filtered over a small column of silica gel (di­ethyl­ether–CHCl₃, 1:1, v/v) to give the title compound (2.56 g, 89%) as colorless needles, mp. 339 – 340 K [Lit. mp. 339-340 K (Anliker et al., 1957)]; ν_max (KBr/cm^-1) 3500 – 2050 (bs, OH), 2955, 2835, 1699, 1504, 1449, 1430, 1307, 1281, 1182, 1127, 927, 916, 865, 795, 717, 499; δ_H (400 MHz, CDCl₃) 2.65 (2H, t, ³J = 7.6 Hz), 2.91 (2H, t, ³J = 7.6 Hz), 6.71 (1H, dd, ³J = 8.4 Hz, ⁴J = 3.2 Hz), 6.75 (1H, d, ⁴J = 3.2 Hz), 6.76 (1H, d, ³J = 8.4 Hz), δ_C (67.8 MHz, CDCl₃) 26.0 (CH₂), 33.9 (CH₂), 55.6 (OCH₃), 55.7 (OCH₃), 111.0 (CH), 111.6 (CH), 116.3 (CH), 129.6 (CH), 151.7 (C_quat), 153.3 (C_quat), 179.7 (C_quat, CO).

Refinement details

All hydrogen atoms were placed in calculated positions with C—H distances of 0.95- 0.99 Å and refined as riding with U_iso(H) = xU_eq(C), where x = 1.5 for methyl and x = 1.2 for all other H-atoms.

Computing details

Data collection: APEX2 (Bruker, 2013); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: SIR2004 (Burla et al., 2007); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2015); molecular graphics: PLATON (Spek, 2009) and Mercury (Macrae et al., 2008); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Figures

Fig. 1. A view of title compound molecule with the atom-numbering scheme. Displacement ellipsoids are shown at the 50% probability level.

3-(2,5-Dimethoxyphenyl)propionic acid

Crystal data

C11H14O4	Dx = 1.324 Mg m^−3
Mr = 210.22	Melting point = 339–340 K
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
a = 24.3212 (10) Å	Cell parameters from 9914 reflections
b = 4.6512 (2) Å	θ = 2.3–31.2°
c = 19.7411 (8) Å	µ = 0.10 mm^−1
β = 109.1782 (6)°	T = 100 K
V = 2109.23 (15) Å^3	Bar, clear light colourless
Z = 8	0.3 × 0.1 × 0.02 mm
F(000) = 896

Data collection

Bruker APEXII CCD diffractometer	2927 reflections with I > 2σ(I)
φ and ω scans	Rint = 0.028
Absorption correction: multi-scan (SADABS; Bruker, 2013)	θmax = 31.3°, θmin = 1.8°
Tmin = 0.604, Tmax = 0.746	h = −35→34
20284 measured reflections	k = −6→6
3224 independent reflections	l = −27→28

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.036	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.107	w = 1/[σ^2(Fo^2) + (0.0556P)^2 + 1.4383P] where P = (Fo^2 + 2Fc^2)/3
S = 1.05	(Δ/σ)max = 0.001
3224 reflections	Δρmax = 0.44 e Å^−3
142 parameters	Δρmin = −0.18 e Å^−3
0 restraints

Special details

Experimental. SADABS-2012/1 (Bruker,2012) was used for absorption correction. wR2(int) was 0.1419 before and 0.0438 after correction. The Ratio of minimum to maximum transmission is 0.8088. The λ/2 correction factor is 0.0015.

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.

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

	x	y	z	Uiso*/Ueq
C1	0.36178 (4)	0.50978 (18)	0.70073 (5)	0.01639 (17)
C10	0.44839 (4)	0.3697 (3)	0.79439 (5)	0.0289 (2)
C11	0.14931 (4)	0.2622 (2)	0.61260 (5)	0.02223 (19)
C2	0.32768 (4)	0.32755 (19)	0.72601 (5)	0.01806 (17)
C3	0.26774 (4)	0.30632 (18)	0.69042 (5)	0.01692 (17)
C4	0.24216 (4)	0.47152 (18)	0.62979 (5)	0.01575 (16)
C5	0.27657 (4)	0.65750 (18)	0.60495 (4)	0.01568 (16)
C6	0.33612 (4)	0.67778 (17)	0.63904 (4)	0.01468 (16)
C7	0.37340 (4)	0.86255 (18)	0.60859 (5)	0.01664 (16)
C8	0.39755 (4)	0.67941 (18)	0.56036 (5)	0.01553 (16)
C9	0.44172 (3)	0.82948 (18)	0.53467 (4)	0.01464 (16)
H10A	0.4311	0.4146	0.8315	0.043*
H10B	0.4901	0.4129	0.8124	0.043*
H10C	0.4427	0.1653	0.7820	0.043*
H11A	0.1506	0.3038	0.6618	0.033*
H11B	0.1648	0.0690	0.6106	0.033*
H11C	0.1090	0.2724	0.5803	0.033*
H2	0.3452	0.2162	0.7679	0.022*
H3	0.2447	0.1796	0.7077	0.020*
H4	0.4791 (8)	0.795 (4)	0.4682 (10)	0.049 (5)*
H5	0.2587	0.7724	0.5638	0.019*
H7A	0.4059	0.9461	0.6481	0.020*
H7B	0.3498	1.0224	0.5804	0.020*
H8A	0.4156	0.5046	0.5871	0.019*
H8B	0.3647	0.6170	0.5181	0.019*
O1	0.42100 (3)	0.53955 (17)	0.73202 (4)	0.02384 (16)
O2	0.18373 (3)	0.46840 (16)	0.59092 (4)	0.02300 (16)
O3	0.46906 (3)	1.04245 (15)	0.56342 (4)	0.02097 (15)
O4	0.44928 (3)	0.70388 (15)	0.47828 (4)	0.02040 (15)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0167 (4)	0.0191 (4)	0.0150 (4)	0.0013 (3)	0.0074 (3)	−0.0003 (3)
C10	0.0211 (4)	0.0448 (6)	0.0197 (4)	0.0072 (4)	0.0049 (3)	0.0065 (4)
C11	0.0206 (4)	0.0207 (4)	0.0263 (4)	−0.0063 (3)	0.0089 (3)	−0.0017 (3)
C2	0.0221 (4)	0.0190 (4)	0.0149 (4)	0.0013 (3)	0.0086 (3)	0.0031 (3)
C3	0.0218 (4)	0.0159 (4)	0.0162 (4)	−0.0015 (3)	0.0104 (3)	0.0008 (3)
C4	0.0170 (4)	0.0154 (3)	0.0162 (4)	−0.0009 (3)	0.0073 (3)	−0.0010 (3)
C5	0.0196 (4)	0.0144 (3)	0.0148 (3)	0.0004 (3)	0.0081 (3)	0.0015 (3)
C6	0.0190 (4)	0.0130 (3)	0.0155 (4)	0.0002 (3)	0.0103 (3)	−0.0010 (3)
C7	0.0201 (4)	0.0144 (3)	0.0200 (4)	−0.0012 (3)	0.0127 (3)	−0.0008 (3)
C8	0.0166 (4)	0.0159 (4)	0.0172 (4)	−0.0024 (3)	0.0099 (3)	−0.0016 (3)
C9	0.0137 (3)	0.0159 (4)	0.0160 (3)	0.0007 (3)	0.0072 (3)	−0.0003 (3)
O1	0.0167 (3)	0.0334 (4)	0.0207 (3)	0.0005 (3)	0.0053 (2)	0.0055 (3)
O2	0.0176 (3)	0.0258 (3)	0.0242 (3)	−0.0045 (2)	0.0049 (3)	0.0060 (3)
O3	0.0239 (3)	0.0205 (3)	0.0238 (3)	−0.0077 (2)	0.0150 (3)	−0.0069 (2)
O4	0.0208 (3)	0.0229 (3)	0.0233 (3)	−0.0074 (2)	0.0151 (3)	−0.0086 (2)

Geometric parameters (Å, º)

C10—H10C	0.9800	C6—C5	1.3854 (12)
C10—H10B	0.9800	C7—H7B	0.9900
C10—H10A	0.9800	C7—H7A	0.9900
C11—H11C	0.9800	C8—C9	1.5019 (11)
C11—H11B	0.9800	C8—C7	1.5312 (11)
C11—H11A	0.9800	C8—H8B	0.9900
C2—C1	1.3882 (12)	C8—H8A	0.9900
C2—H2	0.9500	O1—C10	1.4299 (12)
C3—C4	1.3858 (12)	O1—C1	1.3751 (10)
C3—C2	1.3985 (12)	O2—C11	1.4278 (11)
C3—H3	0.9500	O2—C4	1.3756 (10)
C5—C4	1.3995 (11)	O3—C9	1.2238 (10)
C5—H5	0.9500	O4—H4	0.917 (18)
C6—C1	1.4085 (12)	O4—C9	1.3224 (10)
C6—C7	1.5101 (11)
C1—C2—H2	119.7	C9—C8—H8B	108.6
C1—C2—C3	120.65 (8)	C9—C8—H8A	108.6
C1—C6—C7	120.43 (8)	C9—O4—H4	108.5 (11)
C1—O1—C10	117.01 (7)	H10A—C10—H10C	109.5
C2—C1—C6	120.15 (8)	H10A—C10—H10B	109.5
C2—C3—H3	120.2	H10B—C10—H10C	109.5
C3—C4—C5	119.66 (8)	H11A—C11—H11C	109.5
C3—C2—H2	119.7	H11A—C11—H11B	109.5
C4—C5—H5	119.3	H11B—C11—H11C	109.5
C4—C3—C2	119.53 (8)	H7A—C7—H7B	108.2
C4—C3—H3	120.2	H8A—C8—H8B	107.6
C4—O2—C11	116.09 (7)	O1—C10—H10C	109.5
C5—C6—C1	118.54 (7)	O1—C10—H10B	109.5
C5—C6—C7	120.93 (7)	O1—C10—H10A	109.5
C6—C7—H7B	109.8	O1—C1—C2	124.15 (8)
C6—C7—H7A	109.8	O1—C1—C6	115.71 (7)
C6—C7—C8	109.52 (7)	O2—C11—H11C	109.5
C6—C5—C4	121.46 (8)	O2—C11—H11B	109.5
C6—C5—H5	119.3	O2—C11—H11A	109.5
C7—C8—H8B	108.6	O2—C4—C5	115.98 (7)
C7—C8—H8A	108.6	O2—C4—C3	124.36 (8)
C8—C7—H7B	109.8	O3—C9—C8	124.03 (7)
C8—C7—H7A	109.8	O3—C9—O4	122.90 (8)
C9—C8—C7	114.48 (7)	O4—C9—C8	113.05 (7)
C1—C6—C7—C8	83.52 (9)	C5—C6—C1—C2	0.36 (12)
C1—C6—C5—C4	−1.12 (12)	C5—C6—C1—O1	179.97 (7)
C10—O1—C1—C2	0.15 (13)	C5—C6—C7—C8	−92.96 (9)
C10—O1—C1—C6	−179.45 (8)	C6—C5—C4—C3	0.97 (13)
C11—O2—C4—C5	175.08 (8)	C6—C5—C4—O2	−179.31 (7)
C11—O2—C4—C3	−5.21 (13)	C7—C8—C9—O3	19.85 (12)
C2—C3—C4—C5	−0.03 (13)	C7—C8—C9—O4	−161.63 (7)
C2—C3—C4—O2	−179.73 (8)	C7—C6—C1—C2	−176.20 (8)
C3—C2—C1—C6	0.56 (13)	C7—C6—C1—O1	3.41 (11)
C3—C2—C1—O1	−179.02 (8)	C7—C6—C5—C4	175.42 (7)
C4—C3—C2—C1	−0.73 (13)	C9—C8—C7—C6	−172.25 (7)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···O3^i	0.92 (2)	1.75 (2)	2.6624 (11)	172.1 (18)

Symmetry code: (i) −x+1, −y+2, −z+1.