4-Methyl-2-(2-methyl­anilino)benzoic acid

Liu, C.; Long, S.

doi:10.1107/S2414314623005990

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 8| Part 7| July 2023| x230599

https://doi.org/10.1107/S2414314623005990

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4-Methyl-2-(2-methylanilino)benzoic acid

Chenxin Liu ^a and Sihui Long ^a ^*

^aSchool of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, Hubei 430205, People's Republic of China
^*Correspondence e-mail: sihuilong@wit.edu.cn

Edited by R. J. Butcher, Howard University, USA (Received 15 May 2023; accepted 7 July 2023; online 14 July 2023)

The title compound, C₁₅H₁₅NO₂, was obtained by the reaction of 2-chloro-4-methyl-benzoic acid and o-toluidine using 2-ethoxyethanol as solvent. Crystals of the title compounds were obtained from crystallization in acetone. The molecule in the crystal is twisted with a dihedral angle between the aromatic rings of 50.86 (5)°. In the crystal structure, the molecules associate to form acid–acid hydrogen-bonded dimers linked by pairwise O—H⋯O hydrogen bonds.

Keywords: crystal structure; twisted conformation; acid–acid dimer.

CCDC reference: 2280189

Structure description

Anthranilic acids are compounds with great medicinal value. They play an important role in non-steroidal anti-inflammatory (Masubuchi et al., 1998 ), antibacterial (Abdulkarem et al., 2019 ) and antiviral agents (Inglot 1969 ) and other drugs. The title compound has a methyl group on both aromatic rings (Fig. 1). As a result of steric repulsion, the aromatic rings are not coplanar with a dihedral angle of 50.86 (5)°. In the crystal, two molecules pair up to form a carboxylic acid–carboxylic acid hydrogen-bonded dimer. An intramolecular N1—H1A⋯O2 hydrogen bond (Table 1, Fig. 2) is also observed.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯O2ⁱ	0.82	1.84	2.6570 (17)	174
N1—H1A⋯O2	0.86	2.01	2.6942 (17)	136
Symmetry code: (i) .

Figure 1
Molecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level.

Figure 2
Packing of the molecules in the title compound (for clarity, H atoms not involved in hydrogen bonding are omitted). Hydrogen bonds are indicated by dashed lines.

Synthesis and crystallization

The title compound was prepared by reacting 2-chloro-4-methyl-benzoic acid and o-toluidine in the presence of a catalyst at 403 K (Fig. 3). The product was purified by column chromatography. Single crystals were obtained by slowly evaporating an acetone solution of the compound (Fig. 4).

Figure 3
Reaction scheme.

Figure 4
A representative crystal 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	C₁₅H₁₅NO₂
M_r	241.28
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	293
a, b, c (Å)	9.6678 (8), 10.9294 (11), 11.7231 (8)
β (°)	93.395 (7)
V (Å³)	1236.53 (18)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	0.69
Crystal size (mm)	0.08 × 0.04 × 0.02

Data collection
Diffractometer	SuperNova, Dual, Cu at zero, Eos
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2015 )
T_min, T_max	0.919, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	4437, 2285, 1828
R_int	0.019
(sin θ/λ)_max (Å⁻¹)	0.609

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.045, 0.131, 1.04
No. of reflections	2285
No. of parameters	166
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.25, −0.20
Computer programs: CrysAlis PRO (Rigaku OD, 2015), SHELXS (Sheldrick, 2008 ), SHELXL (Sheldrick, 2015 ), OLEX2 (Dolomanov et al., 2009 ) and Mercury (Macrae et al., 2020 ).

Structural data

CCDC reference: 2280189

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S2414314623005990/bv4047sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314623005990/bv4047Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314623005990/bv4047Isup3.cml

checkCIF report

Computing details top

Data collection: CrysAlis PRO 1.171.38.43f (Rigaku OD, 2015); cell refinement: CrysAlis PRO 1.171.38.43f (Rigaku OD, 2015); data reduction: CrysAlis PRO 1.171.38.43f (Rigaku OD, 2015); program(s) used to solve structure: SHELXS (Sheldrick, 2008); program(s) used to refine structure: SHELXL (Sheldrick, 2015); molecular graphics: Olex2 (Dolomanov et al., 2009), Mercury (Macrae et al., 2020); software used to prepare material for publication: Olex2 (Dolomanov et al., 2009).

4-Methyl-2-(2-methylanilino)benzoic acid top

Crystal data top

C₁₅H₁₅NO₂	F(000) = 512
M_r = 241.28	D_x = 1.296 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54184 Å
a = 9.6678 (8) Å	Cell parameters from 1387 reflections
b = 10.9294 (11) Å	θ = 9.3–69.0°
c = 11.7231 (8) Å	µ = 0.69 mm⁻¹
β = 93.395 (7)°	T = 293 K
V = 1236.53 (18) Å³	Plate, clear light colourless
Z = 4	0.08 × 0.04 × 0.02 mm

Data collection top

SuperNova, Dual, Cu at zero, Eos diffractometer	2285 independent reflections
Radiation source: micro-focus sealed X-ray tube, SuperNova (Cu) X-ray Source	1828 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.019
Detector resolution: 16.0733 pixels mm^-1	θ_max = 70.0°, θ_min = 4.6°
ω scans	h = −11→11
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2015)	k = −12→13
T_min = 0.919, T_max = 1.000	l = −13→10
4437 measured reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.045	H-atom parameters constrained
wR(F²) = 0.131	w = 1/[σ²(F_o²) + (0.0678P)² + 0.2398P] where P = (F_o² + 2F_c²)/3
S = 1.04	(Δ/σ)_max < 0.001
2285 reflections	Δρ_max = 0.25 e Å⁻³
166 parameters	Δρ_min = −0.20 e Å⁻³
0 restraints

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.

Refinement. The positions of H atoms in N1 and O1 were obtained from the difference Fourier map. Other H atoms were positioned geometrically with C—H = 0.93 for aromatic, and constrained to ride on their parent atoms with U_iso(H) = xU_eq(C,O), where x=1.5 for all H atoms.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.32010 (13)	0.52719 (14)	0.45925 (9)	0.0527 (4)
H1	0.396573	0.509295	0.437474	0.079*
O2	0.44087 (12)	0.53328 (13)	0.62639 (9)	0.0487 (4)
N1	0.30228 (14)	0.58797 (15)	0.81250 (11)	0.0434 (4)
H1A	0.377666	0.564178	0.783957	0.052*
C1	0.19420 (15)	0.61667 (15)	0.73583 (13)	0.0332 (4)
C2	0.20410 (16)	0.59559 (14)	0.61709 (13)	0.0333 (4)
C3	0.09126 (17)	0.62616 (17)	0.54234 (13)	0.0409 (4)
H3	0.096893	0.611557	0.464602	0.049*
C4	−0.02712 (18)	0.67684 (17)	0.57997 (15)	0.0455 (4)
H4	−0.100826	0.695348	0.528272	0.055*
C5	−0.03698 (17)	0.70070 (16)	0.69615 (15)	0.0405 (4)
C6	0.07217 (16)	0.66986 (16)	0.77176 (13)	0.0375 (4)
H6	0.064581	0.684862	0.849231	0.045*
C7	0.33051 (17)	0.54979 (15)	0.57000 (13)	0.0365 (4)
C8	−0.1651 (2)	0.7593 (2)	0.73824 (18)	0.0614 (6)
H8A	−0.238018	0.699747	0.739025	0.092*
H8B	−0.193583	0.825546	0.688383	0.092*
H8C	−0.145628	0.790187	0.814164	0.092*
C9	0.30353 (16)	0.59315 (16)	0.93298 (13)	0.0357 (4)
C10	0.41723 (16)	0.64529 (16)	0.99389 (13)	0.0370 (4)
C11	0.41862 (18)	0.64593 (17)	1.11262 (14)	0.0452 (4)
H11	0.494677	0.678781	1.154221	0.054*
C12	0.3104 (2)	0.59922 (19)	1.17011 (14)	0.0492 (5)
H12	0.312562	0.602599	1.249460	0.059*
C13	0.19886 (19)	0.54745 (18)	1.10961 (15)	0.0475 (5)
H13	0.125187	0.516229	1.148058	0.057*
C14	0.19640 (18)	0.54187 (17)	0.99152 (14)	0.0426 (4)
H14	0.122853	0.503693	0.951043	0.051*
C17	0.53483 (18)	0.69949 (18)	0.93333 (16)	0.0495 (5)
H17A	0.582818	0.635765	0.895481	0.074*
H17B	0.597691	0.739472	0.987773	0.074*
H17C	0.499370	0.757976	0.877931	0.074*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0452 (7)	0.0860 (11)	0.0276 (6)	0.0073 (7)	0.0069 (5)	−0.0103 (6)
O2	0.0421 (7)	0.0745 (9)	0.0299 (6)	0.0147 (6)	0.0058 (5)	−0.0046 (6)
N1	0.0337 (7)	0.0716 (11)	0.0253 (7)	0.0098 (7)	0.0055 (5)	−0.0038 (6)
C1	0.0326 (8)	0.0379 (8)	0.0294 (8)	−0.0023 (6)	0.0041 (6)	0.0010 (6)
C2	0.0350 (8)	0.0363 (8)	0.0288 (8)	−0.0023 (6)	0.0046 (6)	−0.0002 (6)
C3	0.0455 (9)	0.0493 (10)	0.0279 (8)	−0.0026 (8)	0.0019 (7)	0.0000 (7)
C4	0.0381 (9)	0.0576 (11)	0.0403 (9)	0.0025 (8)	−0.0021 (7)	0.0065 (8)
C5	0.0374 (9)	0.0438 (9)	0.0407 (9)	0.0020 (7)	0.0076 (7)	0.0061 (7)
C6	0.0388 (9)	0.0450 (9)	0.0295 (8)	0.0025 (7)	0.0082 (6)	0.0001 (7)
C7	0.0419 (9)	0.0422 (9)	0.0260 (7)	−0.0010 (7)	0.0066 (6)	−0.0007 (6)
C8	0.0493 (11)	0.0798 (15)	0.0563 (12)	0.0212 (11)	0.0120 (9)	0.0121 (11)
C9	0.0347 (8)	0.0457 (9)	0.0269 (7)	0.0108 (7)	0.0038 (6)	−0.0002 (7)
C10	0.0364 (8)	0.0400 (9)	0.0347 (8)	0.0094 (7)	0.0029 (6)	−0.0011 (7)
C11	0.0490 (10)	0.0497 (10)	0.0361 (9)	0.0095 (8)	−0.0051 (7)	−0.0046 (8)
C12	0.0610 (11)	0.0618 (12)	0.0251 (8)	0.0175 (9)	0.0044 (8)	0.0031 (8)
C13	0.0463 (10)	0.0587 (11)	0.0390 (9)	0.0109 (9)	0.0151 (8)	0.0124 (8)
C14	0.0363 (8)	0.0560 (11)	0.0358 (9)	0.0029 (8)	0.0046 (7)	0.0026 (8)
C17	0.0411 (9)	0.0543 (11)	0.0531 (11)	−0.0015 (8)	0.0036 (8)	0.0009 (9)

Geometric parameters (Å, º) top

O1—C7	1.3196 (18)	C5—C6	1.379 (2)
O2—C7	1.235 (2)	C5—C8	1.504 (2)
N1—C1	1.374 (2)	C9—C10	1.396 (2)
N1—C9	1.4129 (19)	C9—C14	1.394 (2)
C1—C2	1.420 (2)	C10—C11	1.391 (2)
C1—C6	1.402 (2)	C10—C17	1.498 (2)
C2—C3	1.399 (2)	C11—C12	1.376 (3)
C2—C7	1.459 (2)	C12—C13	1.377 (3)
C3—C4	1.368 (2)	C13—C14	1.385 (2)
C4—C5	1.396 (2)

C1—N1—C9	127.31 (13)	O1—C7—C2	114.81 (14)
N1—C1—C2	120.78 (14)	O2—C7—O1	120.84 (14)
N1—C1—C6	121.27 (14)	O2—C7—C2	124.35 (14)
C6—C1—C2	117.94 (14)	C10—C9—N1	119.17 (14)
C1—C2—C7	122.22 (14)	C14—C9—N1	120.90 (15)
C3—C2—C1	118.69 (14)	C14—C9—C10	119.86 (15)
C3—C2—C7	118.99 (14)	C9—C10—C17	121.04 (15)
C4—C3—C2	122.08 (15)	C11—C10—C9	118.32 (15)
C3—C4—C5	119.82 (15)	C11—C10—C17	120.64 (16)
C4—C5—C8	120.33 (16)	C12—C11—C10	121.71 (17)
C6—C5—C4	119.19 (15)	C11—C12—C13	119.69 (16)
C6—C5—C8	120.47 (16)	C12—C13—C14	119.98 (16)
C5—C6—C1	122.24 (15)	C13—C14—C9	120.36 (17)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O2ⁱ	0.82	1.84	2.6570 (17)	174
N1—H1A···O2	0.86	2.01	2.6942 (17)	136

Symmetry code: (i) −x+1, −y+1, −z+1.

Funding information

CL and SL thank the Natural Science Foundation of Hubie Province for financial support (2014CFB787).

References

Abdulkarem, L. K. & Mahdi, S. H. (2019). J. Phys. Conf. Ser. 1234, 012089–012101. CrossRef CAS Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Inglot, A. D. (1969). J. Gen. Virol. 4, 203–214. CrossRef CAS PubMed Web of Science Google Scholar
Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226–235. Web of Science CrossRef CAS IUCr Journals Google Scholar
Masubuchi, Y., Saito, H. & Horie, T. (1998). J. Pharmacol. Exp. Ther. 287, 208–213. Web of Science CAS PubMed Google Scholar
Rigaku OD (2015). CrysAlis PRO. Rigaku Inc., Tokyo, Japan. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2015). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar

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