4-(3-Chloro­anilino)benzoic acid

Liu, X.; Long, S.

doi:10.1107/S2414314623005989

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 8| Part 7| July 2023| x230598

https://doi.org/10.1107/S2414314623005989

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4-(3-Chloroanilino)benzoic acid

Xiaoting 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 M. Bolte, Goethe-Universität Frankfurt, Germany (Received 15 May 2023; accepted 7 July 2023; online 14 July 2023)

The title compound, C₁₃H₁₀ClNO₂, was synthesized by a Buchwald–Hartwig reaction and its crystal structure was investigated for the first time. Crystallization in a variety of solvents led to the discovery of one crystal form. High-quality single crystals were obtained by slow evaporation and the crystal structure was determined by single-crystal X-ray diffraction. The molecules in the crystal structures are highly twisted [the dihedral angle between the aromatic rings is 34.66 (6)°] and pair up to form acid–acid dimers.

Keywords: crystal structure; 4-(3-chloroanilino)benzoic acid; acid–acid dimers.

CCDC reference: 2280190

Structure description

The title compound (Fig. 1) was first synthesized by Adeniji et al. (2011 ). It is a potent and selective aldo-keto reductase AKR1C2 and AKR1C3 inhibitor, which is efficacious in a prostate cancer model and is a potential therapeutic agent for the treatment of castration-resistant prostate cancer (CRPC) (Adeniji et al., 2012 ). There is only one molecule in the asymmetric unit of the crystal structure. As a result of the repulsion between the carbon-bonded H atoms ortho to NH on both aromatic rings, the molecule is twisted as evidenced by the dihedral angle between the two aromatic rings [34.66 (6)°]. In the crystal, the molecules form acid–acid dimers via O—H⋯O hydrogen bonds (Table 1, Fig. 2).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯O2ⁱ	0.90 (4)	1.78 (4)	2.6359 (19)	160 (4)
Symmetry code: (i) .

Figure 1
Molecular structure of the title compound generated with Mercury (Macrae et al., 2020

), with displacement ellipsoids drawn at the 50% probability level.

Figure 2
Packing of the molecules of the title compound. For clarity, H atoms bonded to C are omitted.

Synthesis and crystallization

In this work, the title compound was successfully prepared by a Buchwald–Hartwig reaction (Fig. 3) (Hou et al., 2015 ) using 4-chlorobenzoic acid and 3-chloroaniline as starting materials. Crystallization was conducted by slow evaporation in avariety of solvents in a clean fume hood. Crystals suitable for single-crystal X-ray diffraction (Fig. 4) were obtained by slow evaporation of an acetonitrile solution.

Figure 3
Synthesis of the title compound.

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	C₁₃H₁₀ClNO₂
M_r	247.67
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	288
a, b, c (Å)	10.8865 (2), 10.31441 (18), 11.0885 (2)
β (°)	113.817 (3)
V (Å³)	1139.08 (5)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	2.88
Crystal size (mm)	0.15 × 0.13 × 0.09

Data collection
Diffractometer	Rigaku Oxford Diffraction, Synergy Custom system, HyPix
Absorption correction	Multi-scan (CrysAlis PRO; Meyer, 2015 $[Rigaku OD (2022). CrysAlis PRO. Rigaku Oxford Diffraction, Tokyo, Japan.]$ )
T_min, T_max	0.375, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	7087, 2278, 2045
R_int	0.025
(sin θ/λ)_max (Å⁻¹)	0.633

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.047, 0.143, 1.08
No. of reflections	2278
No. of parameters	162
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.35, −0.37
Computer programs: CrysAlis PRO (Rigaku OD, 2022 $[Rigaku OD (2022). CrysAlis PRO. Rigaku Oxford Diffraction, Tokyo, Japan.]$ ), SHELXS (Sheldrick, 2008 ), SHELXL2018/3 (Sheldrick, 2015 ), Mercury (Macrae et al., 2020 ) and OLEX2 (Dolomanov et al., 2009 ).

Structural data

CCDC reference: 2280190

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S2414314623005989/bt4139sup1.cif

checkCIF report

Computing details top

Data collection: CrysAlis PRO 1.171.41.113a (Rigaku OD, 2022); cell refinement: CrysAlis PRO 1.171.41.113a (Rigaku OD, 2022); data reduction: CrysAlis PRO 1.171.41.113a (Rigaku OD, 2022); program(s) used to solve structure: SHELXS (Sheldrick, 2008); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015); molecular graphics: Mercury (Macrae et al., 2020); software used to prepare material for publication: Olex2 1.5 (Dolomanov et al., 2009).

4-(3-Chloroanilino)benzoic acid top

Crystal data top

C₁₃H₁₀ClNO₂	F(000) = 512
M_r = 247.67	D_x = 1.444 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54184 Å
a = 10.8865 (2) Å	Cell parameters from 5783 reflections
b = 10.31441 (18) Å	θ = 4.3–77.1°
c = 11.0885 (2) Å	µ = 2.88 mm⁻¹
β = 113.817 (3)°	T = 288 K
V = 1139.08 (5) Å³	Block, clear light colourless
Z = 4	0.15 × 0.13 × 0.09 mm

Data collection top

Rigaku Oxford Diffraction, Synergy Custom system, HyPix diffractometer	2278 independent reflections
Radiation source: Rotating-anode X-ray tube, Rigaku (Cu) X-ray Source	2045 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.025
Detector resolution: 10.0000 pixels mm^-1	θ_max = 77.4°, θ_min = 4.4°
ω scans	h = −13→13
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2022)	k = −12→12
T_min = 0.375, T_max = 1.000	l = −13→14
7087 measured reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.047	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.143	w = 1/[σ²(F_o²) + (0.085P)² + 0.1891P] where P = (F_o² + 2F_c²)/3
S = 1.08	(Δ/σ)_max < 0.001
2278 reflections	Δρ_max = 0.35 e Å⁻³
162 parameters	Δρ_min = −0.37 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 all H atoms were obtained from the difference Fourier map. H atoms bonded to N1 and O1 were freely refined. Other H atoms were positioned geometrically with C—H = 0.93 Å and constraioned to ride on their parent atoms with U_iso(H) = 1.2U_eq(C).

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

	x	y	z	U_iso*/U_eq
Cl1	1.08885 (6)	0.18033 (6)	0.52451 (6)	0.0806 (3)
O1	0.56772 (18)	0.39086 (13)	0.91797 (17)	0.0746 (4)
H1	0.553 (4)	0.394 (4)	0.992 (4)	0.150 (15)*
O2	0.53662 (16)	0.60395 (13)	0.90499 (15)	0.0729 (4)
N1	0.72634 (17)	0.52920 (19)	0.43865 (17)	0.0663 (4)
C1	0.69502 (16)	0.51613 (18)	0.54768 (17)	0.0547 (4)
C2	0.69426 (18)	0.39841 (17)	0.60907 (19)	0.0583 (4)
H2	0.718984	0.322720	0.579069	0.070*
C3	0.65700 (18)	0.39349 (16)	0.71420 (19)	0.0566 (4)
H3	0.658316	0.314588	0.755293	0.068*
C4	0.61751 (16)	0.50519 (15)	0.75936 (17)	0.0511 (4)
C5	0.61631 (19)	0.62229 (17)	0.69628 (19)	0.0594 (4)
H5	0.588815	0.697547	0.724422	0.071*
C6	0.6552 (2)	0.62786 (19)	0.5931 (2)	0.0634 (5)
H6	0.655065	0.707079	0.552966	0.076*
C7	0.57147 (17)	0.50230 (15)	0.86682 (18)	0.0542 (4)
C8	0.80918 (17)	0.4555 (2)	0.39658 (17)	0.0577 (4)
C9	0.89546 (17)	0.3606 (2)	0.47289 (16)	0.0573 (4)
H9	0.897922	0.340034	0.555486	0.069*
C10	0.97786 (19)	0.2970 (2)	0.42486 (18)	0.0612 (5)
C11	0.9792 (2)	0.3250 (2)	0.3038 (2)	0.0717 (6)
H11	1.035995	0.281079	0.273724	0.086*
C12	0.8938 (2)	0.4199 (3)	0.22921 (19)	0.0781 (6)
H12	0.893432	0.441247	0.147575	0.094*
C13	0.8084 (2)	0.4843 (2)	0.27326 (19)	0.0710 (5)
H13	0.750126	0.547161	0.220491	0.085*
H1A	0.707 (3)	0.599 (2)	0.404 (2)	0.076 (7)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0851 (4)	0.0895 (4)	0.0837 (4)	0.0171 (3)	0.0512 (3)	0.0098 (2)
O1	0.1076 (11)	0.0517 (7)	0.0901 (10)	−0.0001 (7)	0.0662 (9)	−0.0001 (6)
O2	0.0978 (10)	0.0509 (7)	0.0929 (10)	−0.0024 (6)	0.0623 (9)	−0.0109 (6)
N1	0.0644 (9)	0.0749 (11)	0.0663 (10)	0.0075 (8)	0.0333 (8)	0.0120 (8)
C1	0.0453 (8)	0.0623 (10)	0.0569 (9)	−0.0007 (7)	0.0212 (7)	0.0001 (7)
C2	0.0618 (10)	0.0515 (9)	0.0731 (11)	−0.0036 (7)	0.0390 (9)	−0.0076 (7)
C3	0.0606 (9)	0.0455 (8)	0.0723 (10)	−0.0027 (7)	0.0358 (8)	−0.0023 (7)
C4	0.0475 (8)	0.0486 (9)	0.0595 (9)	−0.0019 (6)	0.0240 (7)	−0.0047 (6)
C5	0.0633 (10)	0.0486 (9)	0.0721 (11)	0.0066 (7)	0.0332 (9)	0.0002 (7)
C6	0.0666 (10)	0.0548 (10)	0.0750 (11)	0.0087 (8)	0.0351 (9)	0.0136 (8)
C7	0.0550 (9)	0.0467 (9)	0.0659 (10)	−0.0043 (6)	0.0296 (8)	−0.0070 (7)
C8	0.0507 (8)	0.0720 (11)	0.0533 (9)	−0.0104 (8)	0.0242 (7)	−0.0046 (8)
C9	0.0551 (9)	0.0723 (11)	0.0502 (8)	−0.0082 (8)	0.0273 (7)	−0.0039 (7)
C10	0.0599 (9)	0.0727 (11)	0.0584 (10)	−0.0078 (8)	0.0316 (8)	−0.0064 (8)
C11	0.0725 (12)	0.0946 (15)	0.0601 (10)	−0.0076 (10)	0.0392 (9)	−0.0102 (10)
C12	0.0794 (13)	0.1123 (18)	0.0515 (10)	−0.0099 (12)	0.0357 (9)	−0.0001 (10)
C13	0.0648 (11)	0.0932 (15)	0.0552 (10)	−0.0058 (10)	0.0244 (8)	0.0064 (9)

Geometric parameters (Å, º) top

Cl1—C10	1.746 (2)	C4—C7	1.468 (2)
O1—H1	0.90 (4)	C5—H5	0.9300
O1—C7	1.290 (2)	C5—C6	1.372 (3)
O2—C7	1.246 (2)	C6—H6	0.9300
N1—C1	1.389 (2)	C8—C9	1.383 (3)
N1—C8	1.396 (3)	C8—C13	1.396 (3)
N1—H1A	0.80 (3)	C9—H9	0.9300
C1—C2	1.394 (3)	C9—C10	1.380 (3)
C1—C6	1.395 (3)	C10—C11	1.379 (3)
C2—H2	0.9300	C11—H11	0.9300
C2—C3	1.381 (3)	C11—C12	1.374 (3)
C3—H3	0.9300	C12—H12	0.9300
C3—C4	1.392 (2)	C12—C13	1.383 (3)
C4—C5	1.393 (2)	C13—H13	0.9300

C7—O1—H1	115 (3)	O1—C7—C4	117.19 (15)
C1—N1—C8	131.05 (18)	O2—C7—O1	122.19 (16)
C1—N1—H1A	113.1 (18)	O2—C7—C4	120.62 (15)
C8—N1—H1A	114.2 (19)	C9—C8—N1	123.47 (16)
N1—C1—C2	124.18 (17)	C9—C8—C13	118.95 (18)
N1—C1—C6	117.08 (17)	C13—C8—N1	117.50 (19)
C2—C1—C6	118.66 (16)	C8—C9—H9	120.4
C1—C2—H2	119.8	C10—C9—C8	119.14 (16)
C3—C2—C1	120.39 (16)	C10—C9—H9	120.4
C3—C2—H2	119.8	C9—C10—Cl1	118.36 (14)
C2—C3—H3	119.6	C11—C10—Cl1	118.92 (16)
C2—C3—C4	120.79 (16)	C11—C10—C9	122.7 (2)
C4—C3—H3	119.6	C10—C11—H11	121.2
C3—C4—C5	118.60 (16)	C12—C11—C10	117.70 (19)
C3—C4—C7	122.12 (15)	C12—C11—H11	121.2
C5—C4—C7	119.22 (15)	C11—C12—H12	119.4
C4—C5—H5	119.6	C11—C12—C13	121.21 (18)
C6—C5—C4	120.76 (17)	C13—C12—H12	119.4
C6—C5—H5	119.6	C8—C13—H13	119.8
C1—C6—H6	119.6	C12—C13—C8	120.3 (2)
C5—C6—C1	120.78 (17)	C12—C13—H13	119.8
C5—C6—H6	119.6

Cl1—C10—C11—C12	−178.04 (17)	C4—C5—C6—C1	0.9 (3)
N1—C1—C2—C3	−177.58 (17)	C5—C4—C7—O1	176.54 (17)
N1—C1—C6—C5	176.83 (17)	C5—C4—C7—O2	−2.8 (3)
N1—C8—C9—C10	−177.07 (18)	C6—C1—C2—C3	−1.1 (3)
N1—C8—C13—C12	176.3 (2)	C7—C4—C5—C6	−178.23 (17)
C1—N1—C8—C9	−10.4 (3)	C8—N1—C1—C2	−28.5 (3)
C1—N1—C8—C13	172.68 (19)	C8—N1—C1—C6	155.0 (2)
C1—C2—C3—C4	1.1 (3)	C8—C9—C10—Cl1	178.49 (14)
C2—C1—C6—C5	0.1 (3)	C8—C9—C10—C11	0.8 (3)
C2—C3—C4—C5	0.0 (3)	C9—C8—C13—C12	−0.7 (3)
C2—C3—C4—C7	177.14 (16)	C9—C10—C11—C12	−0.4 (3)
C3—C4—C5—C6	−1.0 (3)	C10—C11—C12—C13	−0.7 (3)
C3—C4—C7—O1	−0.6 (3)	C11—C12—C13—C8	1.2 (3)
C3—C4—C7—O2	−179.92 (17)	C13—C8—C9—C10	−0.2 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O2ⁱ	0.90 (4)	1.78 (4)	2.6359 (19)	160 (4)

Symmetry code: (i) −x+1, −y+1, −z+2.

References

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