organic compounds
Methyl 2-(3-chloro-2-methylanilino)pyridine-3-carboxylate
aSchool of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, Hubei 430205, People's Republic of China
*Correspondence e-mail: longsihui@yahoo.com
The title compound, C14H13ClN2O2, was obtained during an attempt to grow single crystals of 4-acetylphenyl 2-[(3-chloro-2-methylphenyl)amino]nicotinate in methanol, and was probably generated by Two intramolecular hydrogen bonds are formed, one between the N—H group and the carbonyl O atom of the ester and the other between the ortho sp2CH group of the benzene ring and the pyridine N atom. Aromatic π–π stacking [shortest centroid–centroid separation = 3.598 (2) Å] is observed in the extended structure.
CCDC reference: 2085247
Structure description
The title compound (I) was first synthesized when preparing of anthranilic acid as possible analgesic and anti-inflammatory agents (Velingkar et al., 2011). In our study, it was obtained during an effort to obtain single crystals of a codrug, 4-acetylphenyl 2-[(3-chloro-2-methylphenyl)amino]nicotinate, by slow evaporation in methanol. Colorless needles were harvested and by single-crystal X-ray diffraction revealed it to be the title compound: by methanol obviously led to the generation of I. The of I consists of one molecule with a near planar conformation as evidenced by the dihedral angle of 5.31 (1)° between the C1–C6 benzene and N2/C8–C12 pyridine rings (Fig. 1). Two intramolecular hydrogen bonds are observed (Table 1), one between the N—H group and the carbonyl oxygen atom of the ester group with a donor–acceptor distance of 2.687 (3) Å, and the other between the ortho sp2C—H grouping of the aniline ring and the pyridine N atom [2.895 (4) Å]: both of these close S(6) rings. The cohesion of the is ensured by aromatic π–π stacking between the benzene and pyridine rings [shortest centroid–centroid separation = 3.598 (2) Å] and hydrophobic interactions (Fig. 2).
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Synthesis and crystallization
4-Acetylphenyl 2-[(3-chloro-2-methylphenyl)amino]nicotinate, synthesized by a condensation reaction between clonixin and paracetamol (Gupta & Moorthy, 2007), was dissolved in HPLC grade methanol to make a The solution underwent slow evaporation at room temperatures and colorless needle-shaped crystals of the title compound (Fig. 3) were harvested after about a week. by methanol likely resulted in the formation of the title compound (Fig. 4).
Refinement
Crystal data, data collection and structure .
details are summarized in Table 2Structural data
CCDC reference: 2085247
https://doi.org/10.1107/S2414314621005393/hb4383sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314621005393/hb4383Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2414314621005393/hb4383Isup3.cml
Data collection: APEX2 (Bruker, 2013); cell
SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: SHELXS (Sheldrick, 2015b); program(s) used to refine structure: SHELXL (Sheldrick, 2015a); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).C14H13ClN2O2 | Dx = 1.424 Mg m−3 |
Mr = 276.71 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, P212121 | Cell parameters from 2539 reflections |
a = 6.919 (2) Å | θ = 2.4–31.0° |
b = 9.653 (3) Å | µ = 0.30 mm−1 |
c = 19.319 (6) Å | T = 296 K |
V = 1290.4 (6) Å3 | Block, yellow |
Z = 4 | 0.2 × 0.2 × 0.1 mm |
F(000) = 576 |
Bruker APEXII CCD diffractometer | 2872 reflections with I > 2σ(I) |
φ and ω scans | Rint = 0.031 |
Absorption correction: multi-scan (SADABS; Bruker, 2013) | θmax = 32.0°, θmin = 2.1° |
Tmin = 0.544, Tmax = 0.746 | h = −9→10 |
7991 measured reflections | k = −11→13 |
4200 independent reflections | l = −14→28 |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.048 | w = 1/[σ2(Fo2) + (0.0816P)2] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.144 | (Δ/σ)max < 0.001 |
S = 1.01 | Δρmax = 0.23 e Å−3 |
4200 reflections | Δρmin = −0.38 e Å−3 |
174 parameters | Absolute structure: Flack x determined using 963 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013) |
0 restraints | Absolute structure parameter: −0.02 (4) |
Primary atom site location: structure-invariant direct methods |
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. H atoms were located in difference Fourier maps and subsequently placed in idealized positions with C—H = 0.95–0.96 and N—H = 0.86 Å: Uiso(H) values were constrained to 1.2Ueq(C,N) or 1.5Ueq(methyl C). |
x | y | z | Uiso*/Ueq | ||
Cl1 | 0.36941 (14) | 0.30941 (9) | 0.76342 (4) | 0.0564 (2) | |
O1 | 0.3954 (4) | −0.07829 (19) | 0.49264 (10) | 0.0550 (6) | |
O2 | 0.4138 (4) | −0.16139 (19) | 0.38542 (11) | 0.0588 (7) | |
N1 | 0.3847 (4) | 0.19868 (19) | 0.50569 (10) | 0.0375 (4) | |
H1 | 0.3865 | 0.1159 | 0.5221 | 0.045* | |
N2 | 0.3731 (4) | 0.3270 (2) | 0.40324 (11) | 0.0396 (5) | |
C1 | 0.3845 (4) | 0.3013 (2) | 0.55605 (12) | 0.0325 (4) | |
C2 | 0.3765 (4) | 0.2557 (2) | 0.62562 (12) | 0.0330 (5) | |
C3 | 0.3778 (4) | 0.3568 (3) | 0.67663 (13) | 0.0377 (5) | |
C4 | 0.3860 (5) | 0.4979 (3) | 0.66203 (15) | 0.0442 (6) | |
H4 | 0.3869 | 0.5631 | 0.6975 | 0.053* | |
C5 | 0.3927 (5) | 0.5379 (3) | 0.59459 (16) | 0.0468 (7) | |
H5 | 0.3978 | 0.6319 | 0.5842 | 0.056* | |
C6 | 0.3921 (5) | 0.4434 (2) | 0.54119 (14) | 0.0416 (6) | |
H6 | 0.3968 | 0.4737 | 0.4955 | 0.050* | |
C7 | 0.3687 (6) | 0.1035 (3) | 0.64212 (15) | 0.0439 (6) | |
H7A | 0.2541 | 0.0639 | 0.6222 | 0.066* | |
H7B | 0.3664 | 0.0910 | 0.6914 | 0.066* | |
H7C | 0.4806 | 0.0584 | 0.6232 | 0.066* | |
C8 | 0.3826 (4) | 0.2042 (2) | 0.43491 (12) | 0.0321 (4) | |
C9 | 0.3880 (4) | 0.0779 (2) | 0.39658 (12) | 0.0338 (5) | |
C10 | 0.3839 (5) | 0.0864 (3) | 0.32512 (13) | 0.0416 (6) | |
H10 | 0.3879 | 0.0061 | 0.2986 | 0.050* | |
C11 | 0.3739 (5) | 0.2146 (3) | 0.29305 (13) | 0.0445 (6) | |
H11 | 0.3708 | 0.2224 | 0.2451 | 0.053* | |
C12 | 0.3689 (5) | 0.3283 (3) | 0.33432 (14) | 0.0439 (6) | |
H12 | 0.3619 | 0.4142 | 0.3127 | 0.053* | |
C13 | 0.3982 (5) | −0.0571 (3) | 0.43094 (14) | 0.0403 (6) | |
C14 | 0.4245 (8) | −0.2972 (3) | 0.4152 (2) | 0.0734 (13) | |
H14A | 0.4497 | −0.3638 | 0.3794 | 0.110* | |
H14B | 0.3041 | −0.3189 | 0.4374 | 0.110* | |
H14C | 0.5269 | −0.2999 | 0.4487 | 0.110* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Cl1 | 0.0711 (5) | 0.0639 (5) | 0.0342 (3) | 0.0059 (5) | 0.0011 (3) | −0.0033 (3) |
O1 | 0.0918 (18) | 0.0370 (9) | 0.0362 (10) | −0.0004 (12) | −0.0012 (12) | 0.0045 (7) |
O2 | 0.103 (2) | 0.0316 (9) | 0.0414 (11) | 0.0015 (11) | −0.0110 (12) | −0.0021 (8) |
N1 | 0.0511 (12) | 0.0297 (8) | 0.0318 (9) | −0.0002 (12) | −0.0003 (10) | 0.0035 (8) |
N2 | 0.0447 (11) | 0.0365 (10) | 0.0377 (11) | 0.0001 (11) | −0.0010 (11) | 0.0080 (8) |
C1 | 0.0316 (10) | 0.0301 (10) | 0.0358 (11) | −0.0001 (11) | −0.0004 (11) | 0.0036 (9) |
C2 | 0.0297 (11) | 0.0329 (10) | 0.0362 (12) | 0.0010 (10) | −0.0007 (11) | 0.0018 (8) |
C3 | 0.0326 (12) | 0.0451 (13) | 0.0353 (12) | 0.0040 (12) | 0.0002 (12) | −0.0033 (10) |
C4 | 0.0447 (15) | 0.0384 (12) | 0.0494 (15) | 0.0013 (13) | −0.0004 (14) | −0.0085 (10) |
C5 | 0.0550 (17) | 0.0327 (11) | 0.0527 (17) | −0.0012 (13) | 0.0016 (16) | −0.0038 (11) |
C6 | 0.0523 (15) | 0.0307 (10) | 0.0417 (13) | 0.0001 (12) | −0.0005 (14) | 0.0052 (9) |
C7 | 0.0562 (16) | 0.0372 (11) | 0.0383 (13) | 0.0008 (14) | −0.0001 (15) | 0.0068 (10) |
C8 | 0.0280 (10) | 0.0353 (10) | 0.0329 (10) | 0.0003 (12) | 0.0011 (10) | 0.0026 (9) |
C9 | 0.0319 (11) | 0.0370 (10) | 0.0326 (11) | −0.0015 (11) | −0.0012 (11) | 0.0009 (9) |
C10 | 0.0428 (14) | 0.0505 (14) | 0.0314 (12) | 0.0037 (14) | −0.0007 (12) | −0.0014 (11) |
C11 | 0.0481 (14) | 0.0561 (15) | 0.0292 (12) | 0.0037 (16) | −0.0002 (12) | 0.0091 (11) |
C12 | 0.0454 (14) | 0.0450 (14) | 0.0415 (14) | 0.0030 (15) | −0.0010 (13) | 0.0122 (10) |
C13 | 0.0482 (16) | 0.0359 (11) | 0.0368 (13) | −0.0026 (12) | −0.0025 (12) | −0.0012 (10) |
C14 | 0.129 (4) | 0.0296 (13) | 0.061 (2) | 0.0016 (18) | −0.019 (2) | 0.0000 (14) |
Cl1—C3 | 1.739 (3) | C5—C6 | 1.377 (4) |
O1—C13 | 1.210 (3) | C6—H6 | 0.9300 |
O2—C13 | 1.341 (3) | C7—H7A | 0.9600 |
O2—C14 | 1.434 (3) | C7—H7B | 0.9600 |
N1—H1 | 0.8600 | C7—H7C | 0.9600 |
N1—C1 | 1.388 (3) | C8—C9 | 1.428 (3) |
N1—C8 | 1.369 (3) | C9—C10 | 1.383 (3) |
N2—C8 | 1.335 (3) | C9—C13 | 1.464 (3) |
N2—C12 | 1.332 (3) | C10—H10 | 0.9300 |
C1—C2 | 1.415 (3) | C10—C11 | 1.386 (4) |
C1—C6 | 1.403 (3) | C11—H11 | 0.9300 |
C2—C3 | 1.387 (3) | C11—C12 | 1.357 (4) |
C2—C7 | 1.504 (3) | C12—H12 | 0.9300 |
C3—C4 | 1.391 (4) | C14—H14A | 0.9600 |
C4—H4 | 0.9300 | C14—H14B | 0.9600 |
C4—C5 | 1.360 (4) | C14—H14C | 0.9600 |
C5—H5 | 0.9300 | ||
C13—O2—C14 | 115.3 (2) | H7A—C7—H7C | 109.5 |
C1—N1—H1 | 113.9 | H7B—C7—H7C | 109.5 |
C8—N1—H1 | 113.9 | N1—C8—C9 | 119.0 (2) |
C8—N1—C1 | 132.2 (2) | N2—C8—N1 | 119.5 (2) |
C12—N2—C8 | 117.9 (2) | N2—C8—C9 | 121.5 (2) |
N1—C1—C2 | 116.3 (2) | C8—C9—C13 | 121.8 (2) |
N1—C1—C6 | 123.7 (2) | C10—C9—C8 | 117.8 (2) |
C6—C1—C2 | 120.0 (2) | C10—C9—C13 | 120.4 (2) |
C1—C2—C7 | 120.4 (2) | C9—C10—H10 | 120.0 |
C3—C2—C1 | 117.1 (2) | C9—C10—C11 | 120.0 (2) |
C3—C2—C7 | 122.5 (2) | C11—C10—H10 | 120.0 |
C2—C3—Cl1 | 119.9 (2) | C10—C11—H11 | 121.3 |
C2—C3—C4 | 123.0 (2) | C12—C11—C10 | 117.4 (2) |
C4—C3—Cl1 | 117.0 (2) | C12—C11—H11 | 121.3 |
C3—C4—H4 | 120.9 | N2—C12—C11 | 125.4 (2) |
C5—C4—C3 | 118.3 (2) | N2—C12—H12 | 117.3 |
C5—C4—H4 | 120.9 | C11—C12—H12 | 117.3 |
C4—C5—H5 | 119.0 | O1—C13—O2 | 121.4 (2) |
C4—C5—C6 | 122.0 (2) | O1—C13—C9 | 126.6 (2) |
C6—C5—H5 | 119.0 | O2—C13—C9 | 112.0 (2) |
C1—C6—H6 | 120.2 | O2—C14—H14A | 109.5 |
C5—C6—C1 | 119.6 (3) | O2—C14—H14B | 109.5 |
C5—C6—H6 | 120.2 | O2—C14—H14C | 109.5 |
C2—C7—H7A | 109.5 | H14A—C14—H14B | 109.5 |
C2—C7—H7B | 109.5 | H14A—C14—H14C | 109.5 |
C2—C7—H7C | 109.5 | H14B—C14—H14C | 109.5 |
H7A—C7—H7B | 109.5 | ||
Cl1—C3—C4—C5 | 180.0 (3) | C7—C2—C3—Cl1 | −0.2 (4) |
N1—C1—C2—C3 | 179.5 (3) | C7—C2—C3—C4 | 179.6 (3) |
N1—C1—C2—C7 | 0.0 (4) | C8—N1—C1—C2 | 176.7 (3) |
N1—C1—C6—C5 | −179.5 (3) | C8—N1—C1—C6 | −3.5 (5) |
N1—C8—C9—C10 | 179.4 (3) | C8—N2—C12—C11 | −0.2 (5) |
N1—C8—C9—C13 | −0.8 (4) | C8—C9—C10—C11 | −0.3 (4) |
N2—C8—C9—C10 | 0.3 (4) | C8—C9—C13—O1 | 3.2 (5) |
N2—C8—C9—C13 | −179.9 (3) | C8—C9—C13—O2 | −176.2 (3) |
C1—N1—C8—N2 | −2.3 (5) | C9—C10—C11—C12 | 0.1 (5) |
C1—N1—C8—C9 | 178.6 (3) | C10—C9—C13—O1 | −177.0 (3) |
C1—C2—C3—Cl1 | −179.7 (2) | C10—C9—C13—O2 | 3.6 (4) |
C1—C2—C3—C4 | 0.2 (4) | C10—C11—C12—N2 | 0.1 (5) |
C2—C1—C6—C5 | 0.3 (4) | C12—N2—C8—N1 | −179.2 (3) |
C2—C3—C4—C5 | 0.1 (5) | C12—N2—C8—C9 | 0.0 (4) |
C3—C4—C5—C6 | −0.2 (5) | C13—C9—C10—C11 | 179.9 (3) |
C4—C5—C6—C1 | 0.0 (5) | C14—O2—C13—O1 | 0.6 (5) |
C6—C1—C2—C3 | −0.3 (4) | C14—O2—C13—C9 | −180.0 (3) |
C6—C1—C2—C7 | −179.8 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O1 | 0.86 | 1.96 | 2.687 (3) | 142 |
C6—H6···N2 | 0.93 | 2.28 | 2.895 (4) | 123 |
Funding information
The authors thank the Natural Science Foundation of Hubei Province for financial support (2014CFB787).
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