2-[(2-Methyl­phen­yl)amino]­quinoline-3-carb­oxy­lic acid

Guo, S.; Long, S.

doi:10.1107/S2414314626005547

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 11| Part 5| May 2026| x260554

https://doi.org/10.1107/S2414314626005547

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2-[(2-Methylphenyl)amino]quinoline-3-carboxylic acid

Shuyuan Guo ^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: [email protected]

Edited by W. T. A. Harrison, University of Aberdeen, United Kingdom (Received 14 May 2026; accepted 26 May 2026; online 29 May 2026)

In the title compound, C₁₇H₁₄N₂O₂, the dihedral angle between the quinoline ring system and the pendant phenyl ring is 6.19 (6)° and an intramolecular N—H⋯O hydrogen bond supports the near-planar conformation. In the extended structure, the molecules associate to form centrosymmetric carboxylic acid dimers linked by pairs of O—H⋯O hydrogen bonds.

Keywords: hydrogen bond; acid–acid dimer synthon; single crystal.

CCDC reference: 2556750

Structure description

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of drugs that do not contain a steroidal structure but possess anti-inflammatory, analgesic, and antipyretic effects (Ho et al., 2018 ). NSAIDs mainly exert their anti-inflammatory and analgesic effects by inhibiting cyclooxygenase (COX), thereby reducing the production of prostaglandins. Salicylic acid was the first NSAID to be discovered (Jiang et al., 2018 ). Following salicylic acid, benzoic acid and nicotinic acid derivatives became important NSAIDs, exemplified by tolfenamic acid and clonixin. These anti-inflammatory drugs have been found to exhibit polymorphism. For example, tolfenamic acid has been found to have nine crystal forms (Subaiea et al., 2011 ). As part of our studies in this area, we now describe the synthesis and structure of the title compound, C₁₇H₁₄N₂O₂ (I).

Compound (I) (Fig. 1) is an analogue of 2-(phenylamino)nicotinic acid (Long et al., 2008 ), which is a compound with rich polymorphism. In the new compound, a quinoline ring replaces the pyridine ring. The C1–C9/N1 quinoline and pendant C10–C15 phenyl rings are almost coplanar, with a dihedral angle of 6.19 (6)° and an intramolecular N—H⋯O hydrogen bond (Table 1) supports the near-planar conformation. In the extended structure, the molecules associate to form centrosymmetric carboxylic-acid dimers linked by pairs of O—H⋯O hydrogen bonds (Fig. 2).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2⋯O2	0.86	1.97	2.6956 (14)	141
O1—H1⋯O2ⁱ	0.82	1.85	2.6684 (13)	177
Symmetry code: (i) .

Figure 1
The molecular structure of (I) drawn at the 50% probability level. The intramolecular hydrogen bond is shown as a dashed line.

Figure 2
Packing of the molecules in (I) with hydrogen bonds shown as red dashed lines (for clarity, H atoms not involved in hydrogen bonding are omitted).

Synthesis and crystallization

The title compound was synthesized in two steps using a Buchwald–Hartwig cross-coupling reaction and a hydrolysis reaction (Fig. 3). The compound was purified by column chromatography. Single crystals in the form of yellow needles were obtained by slowly evaporating an acetone solution of the title compound.

Figure 3
Synthesis scheme for (I).

Refinement

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

Table 2
Experimental details

Crystal data
Chemical formula	C₁₇H₁₄N₂O₂
M_r	278.30
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	300
a, b, c (Å)	4.9122 (1), 24.0804 (6), 11.5773 (2)
β (°)	90.220 (2)
V (Å³)	1369.44 (5)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	0.73
Crystal size (mm)	0.2 × 0.08 × 0.07

Data collection
Diffractometer	ROD, Synergy Custom system, HyPix
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2024 )
T_min, T_max	0.606, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	11254, 2830, 2380
R_int	0.032
(sin θ/λ)_max (Å⁻¹)	0.633

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.040, 0.121, 1.06
No. of reflections	2830
No. of parameters	193
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.19, −0.14
Computer programs: CrysAlis PRO (Rigaku OD, 2024), SHELXT (Sheldrick, 2015a ), SHELXL2018/3 (Sheldrick, 2015b ) a OLEX2 (Dolomanov et al., 2009 ).

Structural data

CCDC reference: 2556750

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S2414314626005547/hb4562sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314626005547/hb4562Isup3.hkl

checkCIF report

Computing details top

2-[(2-Methylphenyl)amino]quinoline-3-carboxylic acid top

Crystal data top

C₁₇H₁₄N₂O₂	F(000) = 584
M_r = 278.30	D_x = 1.350 Mg m⁻³
Monoclinic, P2₁/n	Cu Kα radiation, λ = 1.54184 Å
a = 4.9122 (1) Å	Cell parameters from 6020 reflections
b = 24.0804 (6) Å	θ = 3.7–77.1°
c = 11.5773 (2) Å	µ = 0.73 mm⁻¹
β = 90.220 (2)°	T = 300 K
V = 1369.44 (5) Å³	Needle, clear dark yellow
Z = 4	0.2 × 0.08 × 0.07 mm

Data collection top

ROD, Synergy Custom system, HyPix diffractometer	2830 independent reflections
Radiation source: Rotating-anode X-ray tube, Rigaku (Cu) X-ray Source	2380 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.032
Detector resolution: 10.0000 pixels mm^-1	θ_max = 77.6°, θ_min = 3.7°
ω scans	h = −5→6
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2024)	k = −30→30
T_min = 0.606, T_max = 1.000	l = −14→14
11254 measured reflections

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.040	w = 1/[σ²(F_o²) + (0.0605P)² + 0.1663P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.121	(Δ/σ)_max < 0.001
S = 1.06	Δρ_max = 0.19 e Å⁻³
2830 reflections	Δρ_min = −0.14 e Å⁻³
193 parameters	Extinction correction: SHELXL2018/3 (Sheldrick 2015b), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0043 (8)
Primary atom site location: dual

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 H atoms were placed in idealized locations and refined as riding atoms.

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

	x	y	z	U_iso*/U_eq
O1	0.86071 (19)	0.50007 (4)	0.64825 (8)	0.0544 (3)
H1	0.972645	0.514724	0.605628	0.082*
O2	0.76184 (18)	0.45416 (4)	0.48683 (8)	0.0528 (3)
N1	0.1504 (2)	0.36553 (5)	0.67276 (10)	0.0489 (3)
N2	0.3664 (2)	0.37672 (5)	0.49696 (10)	0.0514 (3)
H2	0.493564	0.394442	0.461808	0.062*
C1	0.3361 (2)	0.39115 (5)	0.60958 (11)	0.0434 (3)
C2	0.5062 (2)	0.43478 (5)	0.65729 (10)	0.0427 (3)
C3	0.4650 (3)	0.44993 (6)	0.76930 (11)	0.0487 (3)
H3	0.571032	0.478019	0.801326	0.058*
C4	0.2651 (3)	0.42393 (6)	0.83770 (11)	0.0485 (3)
C5	0.2115 (3)	0.43787 (8)	0.95348 (13)	0.0656 (4)
H5	0.306527	0.466831	0.988248	0.079*
C6	0.0207 (3)	0.40921 (8)	1.01528 (13)	0.0688 (4)
H6	−0.013247	0.418603	1.091801	0.083*
C7	−0.1219 (3)	0.36607 (7)	0.96347 (14)	0.0636 (4)
H7	−0.249664	0.346493	1.006340	0.076*
C8	−0.0788 (3)	0.35180 (6)	0.85132 (13)	0.0569 (4)
H8	−0.177882	0.322935	0.818292	0.068*
C9	0.1164 (2)	0.38075 (5)	0.78466 (11)	0.0461 (3)
C10	0.2272 (3)	0.33793 (6)	0.42729 (12)	0.0493 (3)
C11	0.2962 (3)	0.33752 (6)	0.31000 (12)	0.0520 (3)
C12	0.1663 (3)	0.29969 (7)	0.23774 (14)	0.0630 (4)
H12	0.212688	0.298684	0.159966	0.076*
C13	−0.0303 (4)	0.26344 (7)	0.27837 (17)	0.0706 (5)
H13	−0.116345	0.238710	0.228478	0.085*
C14	−0.0961 (4)	0.26463 (7)	0.39330 (17)	0.0692 (4)
H14	−0.228135	0.240482	0.421178	0.083*
C15	0.0303 (3)	0.30104 (7)	0.46839 (14)	0.0619 (4)
H15	−0.015566	0.301025	0.546256	0.074*
C16	0.5042 (3)	0.37707 (7)	0.26173 (13)	0.0626 (4)
H16A	0.450583	0.414562	0.278322	0.094*
H16B	0.516342	0.372110	0.179635	0.094*
H16C	0.678339	0.369766	0.296465	0.094*
C17	0.7195 (2)	0.46328 (5)	0.58959 (11)	0.0432 (3)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0490 (5)	0.0645 (6)	0.0498 (5)	−0.0156 (4)	0.0073 (4)	−0.0006 (4)
O2	0.0487 (5)	0.0648 (6)	0.0449 (5)	−0.0131 (4)	0.0084 (4)	0.0016 (4)
N1	0.0468 (6)	0.0531 (6)	0.0468 (6)	−0.0057 (5)	0.0081 (4)	0.0046 (5)
N2	0.0487 (6)	0.0606 (7)	0.0450 (6)	−0.0125 (5)	0.0084 (5)	−0.0009 (5)
C1	0.0383 (6)	0.0480 (6)	0.0439 (6)	0.0002 (5)	0.0035 (5)	0.0063 (5)
C2	0.0363 (6)	0.0493 (7)	0.0426 (6)	0.0002 (5)	0.0024 (5)	0.0065 (5)
C3	0.0444 (6)	0.0566 (7)	0.0450 (7)	−0.0059 (5)	0.0017 (5)	0.0022 (6)
C4	0.0438 (6)	0.0587 (8)	0.0430 (6)	0.0003 (5)	0.0047 (5)	0.0062 (5)
C5	0.0653 (9)	0.0845 (11)	0.0470 (8)	−0.0111 (8)	0.0093 (6)	−0.0048 (7)
C6	0.0693 (9)	0.0914 (12)	0.0458 (8)	−0.0020 (9)	0.0164 (7)	0.0040 (8)
C7	0.0584 (8)	0.0751 (10)	0.0576 (8)	−0.0008 (7)	0.0194 (7)	0.0149 (8)
C8	0.0542 (7)	0.0584 (8)	0.0584 (8)	−0.0066 (6)	0.0134 (6)	0.0084 (6)
C9	0.0420 (6)	0.0505 (7)	0.0460 (6)	0.0039 (5)	0.0063 (5)	0.0079 (5)
C10	0.0457 (6)	0.0515 (7)	0.0507 (7)	0.0004 (5)	0.0007 (5)	−0.0024 (6)
C11	0.0498 (7)	0.0555 (7)	0.0506 (7)	0.0092 (6)	0.0005 (5)	−0.0038 (6)
C12	0.0714 (9)	0.0627 (9)	0.0550 (8)	0.0123 (7)	−0.0063 (7)	−0.0105 (7)
C13	0.0747 (10)	0.0566 (9)	0.0803 (12)	0.0010 (7)	−0.0198 (9)	−0.0141 (8)
C14	0.0666 (9)	0.0608 (9)	0.0802 (11)	−0.0133 (7)	−0.0060 (8)	−0.0029 (8)
C15	0.0618 (8)	0.0632 (9)	0.0606 (9)	−0.0130 (7)	0.0022 (7)	−0.0012 (7)
C16	0.0662 (9)	0.0747 (10)	0.0470 (7)	0.0003 (7)	0.0132 (6)	−0.0026 (7)
C17	0.0371 (6)	0.0488 (7)	0.0437 (6)	−0.0009 (5)	0.0000 (5)	0.0053 (5)

Geometric parameters (Å, º) top

O1—H1	0.8200	C7—H7	0.9300
O1—C17	1.3129 (16)	C7—C8	1.360 (2)
O2—C17	1.2284 (15)	C8—H8	0.9300
N1—C1	1.3239 (15)	C8—C9	1.4164 (17)
N1—C9	1.3573 (17)	C10—C11	1.4008 (19)
N2—H2	0.8600	C10—C15	1.398 (2)
N2—C1	1.3582 (17)	C11—C12	1.390 (2)
N2—C10	1.4096 (18)	C11—C16	1.506 (2)
C1—C2	1.4503 (18)	C12—H12	0.9300
C2—C3	1.3629 (18)	C12—C13	1.385 (3)
C2—C17	1.4797 (16)	C13—H13	0.9300
C3—H3	0.9300	C13—C14	1.371 (3)
C3—C4	1.4105 (18)	C14—H14	0.9300
C4—C5	1.408 (2)	C14—C15	1.380 (2)
C4—C9	1.410 (2)	C15—H15	0.9300
C5—H5	0.9300	C16—H16A	0.9600
C5—C6	1.368 (2)	C16—H16B	0.9600
C6—H6	0.9300	C16—H16C	0.9600
C6—C7	1.388 (3)

C17—O1—H1	109.5	N1—C9—C8	118.25 (13)
C1—N1—C9	119.29 (12)	C4—C9—C8	118.43 (12)
C1—N2—H2	114.2	C11—C10—N2	116.15 (12)
C1—N2—C10	131.61 (11)	C15—C10—N2	124.14 (13)
C10—N2—H2	114.2	C15—C10—C11	119.72 (13)
N1—C1—N2	119.31 (12)	C10—C11—C16	121.48 (13)
N1—C1—C2	121.62 (12)	C12—C11—C10	118.41 (14)
N2—C1—C2	119.07 (11)	C12—C11—C16	120.11 (13)
C1—C2—C17	122.84 (11)	C11—C12—H12	119.1
C3—C2—C1	117.96 (11)	C13—C12—C11	121.83 (15)
C3—C2—C17	119.20 (12)	C13—C12—H12	119.1
C2—C3—H3	119.3	C12—C13—H13	120.5
C2—C3—C4	121.44 (13)	C14—C13—C12	118.91 (15)
C4—C3—H3	119.3	C14—C13—H13	120.5
C5—C4—C3	124.19 (14)	C13—C14—H14	119.4
C5—C4—C9	119.48 (12)	C13—C14—C15	121.18 (16)
C9—C4—C3	116.33 (12)	C15—C14—H14	119.4
C4—C5—H5	119.7	C10—C15—H15	120.0
C6—C5—C4	120.58 (16)	C14—C15—C10	119.94 (15)
C6—C5—H5	119.7	C14—C15—H15	120.0
C5—C6—H6	120.1	C11—C16—H16A	109.5
C5—C6—C7	119.81 (15)	C11—C16—H16B	109.5
C7—C6—H6	120.1	C11—C16—H16C	109.5
C6—C7—H7	119.3	H16A—C16—H16B	109.5
C8—C7—C6	121.42 (14)	H16A—C16—H16C	109.5
C8—C7—H7	119.3	H16B—C16—H16C	109.5
C7—C8—H8	119.9	O1—C17—C2	114.38 (11)
C7—C8—C9	120.26 (15)	O2—C17—O1	122.04 (11)
C9—C8—H8	119.9	O2—C17—C2	123.57 (11)
N1—C9—C4	123.31 (11)

N1—C1—C2—C3	−1.65 (19)	C4—C5—C6—C7	−0.2 (3)
N1—C1—C2—C17	178.61 (11)	C5—C4—C9—N1	178.35 (13)
N2—C1—C2—C3	177.62 (12)	C5—C4—C9—C8	−1.5 (2)
N2—C1—C2—C17	−2.12 (18)	C5—C6—C7—C8	−0.8 (3)
N2—C10—C11—C12	179.45 (13)	C6—C7—C8—C9	0.5 (2)
N2—C10—C11—C16	−1.0 (2)	C7—C8—C9—N1	−179.25 (14)
N2—C10—C15—C14	179.76 (15)	C7—C8—C9—C4	0.6 (2)
C1—N1—C9—C4	1.7 (2)	C9—N1—C1—N2	−178.68 (12)
C1—N1—C9—C8	−178.45 (12)	C9—N1—C1—C2	0.59 (19)
C1—N2—C10—C11	174.13 (13)	C9—C4—C5—C6	1.3 (2)
C1—N2—C10—C15	−6.0 (2)	C10—N2—C1—N1	1.6 (2)
C1—C2—C3—C4	0.49 (19)	C10—N2—C1—C2	−177.73 (13)
C1—C2—C17—O1	−177.35 (11)	C10—C11—C12—C13	1.0 (2)
C1—C2—C17—O2	3.29 (19)	C11—C10—C15—C14	−0.3 (2)
C2—C3—C4—C5	−179.58 (14)	C11—C12—C13—C14	−0.7 (2)
C2—C3—C4—C9	1.5 (2)	C12—C13—C14—C15	−0.1 (3)
C3—C2—C17—O1	2.91 (17)	C13—C14—C15—C10	0.6 (3)
C3—C2—C17—O2	−176.45 (12)	C15—C10—C11—C12	−0.5 (2)
C3—C4—C5—C6	−177.53 (15)	C15—C10—C11—C16	179.12 (14)
C3—C4—C9—N1	−2.7 (2)	C16—C11—C12—C13	−178.60 (15)
C3—C4—C9—C8	177.40 (12)	C17—C2—C3—C4	−179.76 (12)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O2	0.86	1.97	2.6956 (14)	141
O1—H1···O2ⁱ	0.82	1.85	2.6684 (13)	177

Symmetry code: (i) −x+2, −y+1, −z+1.

Acknowledgements

SYG and SL thank the Graduate Innovation Fund of WIT for financial support.

References

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