organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2414-3146

Methyl 2-(3-chloro-2-methyl­anilino)pyridine-3-carboxyl­ate

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aSchool of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, Hubei 430205, People's Republic of China
*Correspondence e-mail: longsihui@yahoo.com

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 13 May 2021; accepted 22 May 2021; online 25 May 2021)

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 alcoholysis. 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 ππ stacking [shortest centroid–centroid separation = 3.598 (2) Å] is observed in the extended structure.

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

The title compound (I) was first synthesized when preparing esters of anthranilic acid as possible analgesic and anti-inflammatory agents (Velingkar et al., 2011[Velingkar, V. S., Desai, D. M. & Panda, V. S. (2011). Int. J. Drug Des. Discov. 2, 548-558.]). 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 structure determination by single-crystal X-ray diffraction revealed it to be the title compound: alcoholysis by methanol obviously led to the generation of I. The asymmetric unit 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[link]). Two intra­molecular hydrogen bonds are observed (Table 1[link]), 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 crystal structure is ensured by aromatic ππ stacking between the benzene and pyridine rings [shortest centroid–centroid separation = 3.598 (2) Å] and hydro­phobic inter­actions (Fig. 2[link]).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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
[Figure 1]
Figure 1
The mol­ecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level.
[Figure 2]
Figure 2
(a) Packing of the mol­ecules in the title compound viewed along [100] with the intra­molecular hydrogen bonds indicated by green dashed lines; (b) packing of the mol­ecules in the title compound viewed along [001].

Synthesis and crystallization

4-Acetyl­phenyl 2-[(3-chloro-2-methyl­phen­yl)amino]­nicotin­ate, synthesized by a condensation reaction between clonixin and paracetamol (Gupta & Moorthy, 2007[Gupta, S. P. B. N. & Moorthy, N. S. H. N. (2007). Trends Appl. Sci. Res. 2, 165-169.]), was dissolved in HPLC grade methanol to make a saturated solution. The solution underwent slow evaporation at room temperatures and colorless needle-shaped crystals of the title compound (Fig. 3[link]) were harvested after about a week. Alcoholysis by methanol likely resulted in the formation of the title compound (Fig. 4[link]).

[Figure 3]
Figure 3
A representative crystal of I.
[Figure 4]
Figure 4
Reaction scheme.

Refinement

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

Table 2
Experimental details

Crystal data
Chemical formula C14H13ClN2O2
Mr 276.71
Crystal system, space group Orthorhombic, P212121
Temperature (K) 296
a, b, c (Å) 6.919 (2), 9.653 (3), 19.319 (6)
V3) 1290.4 (6)
Z 4
Radiation type Mo Kα
μ (mm−1) 0.30
Crystal size (mm) 0.2 × 0.2 × 0.1
 
Data collection
Diffractometer Bruker APEXII CCD
Absorption correction Multi-scan (SADABS; Bruker, 2013[Bruker (2013). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.544, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections 7991, 4200, 2872
Rint 0.031
(sin θ/λ)max−1) 0.746
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.048, 0.144, 1.01
No. of reflections 4200
No. of parameters 174
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.23, −0.39
Absolute structure Flack x determined using 963 quotients [(I+)−(I)]/[(I+)+(I)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.])
Absolute structure parameter −0.02 (4)
Computer programs: APEX2 and SAINT (Bruker, 2013[Bruker (2013). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXS (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), SHELXL (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]) and OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]).

Structural data


Computing details top

Data collection: APEX2 (Bruker, 2013); cell refinement: 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).

Methyl 2-(3-chloro-2-methylanilino)pyridine-3-carboxylate top
Crystal data top
C14H13ClN2O2Dx = 1.424 Mg m3
Mr = 276.71Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121Cell parameters from 2539 reflections
a = 6.919 (2) Åθ = 2.4–31.0°
b = 9.653 (3) ŵ = 0.30 mm1
c = 19.319 (6) ÅT = 296 K
V = 1290.4 (6) Å3Block, yellow
Z = 40.2 × 0.2 × 0.1 mm
F(000) = 576
Data collection top
Bruker APEXII CCD
diffractometer
2872 reflections with I > 2σ(I)
φ and ω scansRint = 0.031
Absorption correction: multi-scan
(SADABS; Bruker, 2013)
θmax = 32.0°, θmin = 2.1°
Tmin = 0.544, Tmax = 0.746h = 910
7991 measured reflectionsk = 1113
4200 independent reflectionsl = 1428
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-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 = 1.01Δρmax = 0.23 e Å3
4200 reflectionsΔρmin = 0.38 e Å3
174 parametersAbsolute structure: Flack x determined using 963 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
0 restraintsAbsolute structure parameter: 0.02 (4)
Primary atom site location: structure-invariant direct methods
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. 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).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Cl10.36941 (14)0.30941 (9)0.76342 (4)0.0564 (2)
O10.3954 (4)0.07829 (19)0.49264 (10)0.0550 (6)
O20.4138 (4)0.16139 (19)0.38542 (11)0.0588 (7)
N10.3847 (4)0.19868 (19)0.50569 (10)0.0375 (4)
H10.38650.11590.52210.045*
N20.3731 (4)0.3270 (2)0.40324 (11)0.0396 (5)
C10.3845 (4)0.3013 (2)0.55605 (12)0.0325 (4)
C20.3765 (4)0.2557 (2)0.62562 (12)0.0330 (5)
C30.3778 (4)0.3568 (3)0.67663 (13)0.0377 (5)
C40.3860 (5)0.4979 (3)0.66203 (15)0.0442 (6)
H40.38690.56310.69750.053*
C50.3927 (5)0.5379 (3)0.59459 (16)0.0468 (7)
H50.39780.63190.58420.056*
C60.3921 (5)0.4434 (2)0.54119 (14)0.0416 (6)
H60.39680.47370.49550.050*
C70.3687 (6)0.1035 (3)0.64212 (15)0.0439 (6)
H7A0.25410.06390.62220.066*
H7B0.36640.09100.69140.066*
H7C0.48060.05840.62320.066*
C80.3826 (4)0.2042 (2)0.43491 (12)0.0321 (4)
C90.3880 (4)0.0779 (2)0.39658 (12)0.0338 (5)
C100.3839 (5)0.0864 (3)0.32512 (13)0.0416 (6)
H100.38790.00610.29860.050*
C110.3739 (5)0.2146 (3)0.29305 (13)0.0445 (6)
H110.37080.22240.24510.053*
C120.3689 (5)0.3283 (3)0.33432 (14)0.0439 (6)
H120.36190.41420.31270.053*
C130.3982 (5)0.0571 (3)0.43094 (14)0.0403 (6)
C140.4245 (8)0.2972 (3)0.4152 (2)0.0734 (13)
H14A0.44970.36380.37940.110*
H14B0.30410.31890.43740.110*
H14C0.52690.29990.44870.110*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0711 (5)0.0639 (5)0.0342 (3)0.0059 (5)0.0011 (3)0.0033 (3)
O10.0918 (18)0.0370 (9)0.0362 (10)0.0004 (12)0.0012 (12)0.0045 (7)
O20.103 (2)0.0316 (9)0.0414 (11)0.0015 (11)0.0110 (12)0.0021 (8)
N10.0511 (12)0.0297 (8)0.0318 (9)0.0002 (12)0.0003 (10)0.0035 (8)
N20.0447 (11)0.0365 (10)0.0377 (11)0.0001 (11)0.0010 (11)0.0080 (8)
C10.0316 (10)0.0301 (10)0.0358 (11)0.0001 (11)0.0004 (11)0.0036 (9)
C20.0297 (11)0.0329 (10)0.0362 (12)0.0010 (10)0.0007 (11)0.0018 (8)
C30.0326 (12)0.0451 (13)0.0353 (12)0.0040 (12)0.0002 (12)0.0033 (10)
C40.0447 (15)0.0384 (12)0.0494 (15)0.0013 (13)0.0004 (14)0.0085 (10)
C50.0550 (17)0.0327 (11)0.0527 (17)0.0012 (13)0.0016 (16)0.0038 (11)
C60.0523 (15)0.0307 (10)0.0417 (13)0.0001 (12)0.0005 (14)0.0052 (9)
C70.0562 (16)0.0372 (11)0.0383 (13)0.0008 (14)0.0001 (15)0.0068 (10)
C80.0280 (10)0.0353 (10)0.0329 (10)0.0003 (12)0.0011 (10)0.0026 (9)
C90.0319 (11)0.0370 (10)0.0326 (11)0.0015 (11)0.0012 (11)0.0009 (9)
C100.0428 (14)0.0505 (14)0.0314 (12)0.0037 (14)0.0007 (12)0.0014 (11)
C110.0481 (14)0.0561 (15)0.0292 (12)0.0037 (16)0.0002 (12)0.0091 (11)
C120.0454 (14)0.0450 (14)0.0415 (14)0.0030 (15)0.0010 (13)0.0122 (10)
C130.0482 (16)0.0359 (11)0.0368 (13)0.0026 (12)0.0025 (12)0.0012 (10)
C140.129 (4)0.0296 (13)0.061 (2)0.0016 (18)0.019 (2)0.0000 (14)
Geometric parameters (Å, º) top
Cl1—C31.739 (3)C5—C61.377 (4)
O1—C131.210 (3)C6—H60.9300
O2—C131.341 (3)C7—H7A0.9600
O2—C141.434 (3)C7—H7B0.9600
N1—H10.8600C7—H7C0.9600
N1—C11.388 (3)C8—C91.428 (3)
N1—C81.369 (3)C9—C101.383 (3)
N2—C81.335 (3)C9—C131.464 (3)
N2—C121.332 (3)C10—H100.9300
C1—C21.415 (3)C10—C111.386 (4)
C1—C61.403 (3)C11—H110.9300
C2—C31.387 (3)C11—C121.357 (4)
C2—C71.504 (3)C12—H120.9300
C3—C41.391 (4)C14—H14A0.9600
C4—H40.9300C14—H14B0.9600
C4—C51.360 (4)C14—H14C0.9600
C5—H50.9300
C13—O2—C14115.3 (2)H7A—C7—H7C109.5
C1—N1—H1113.9H7B—C7—H7C109.5
C8—N1—H1113.9N1—C8—C9119.0 (2)
C8—N1—C1132.2 (2)N2—C8—N1119.5 (2)
C12—N2—C8117.9 (2)N2—C8—C9121.5 (2)
N1—C1—C2116.3 (2)C8—C9—C13121.8 (2)
N1—C1—C6123.7 (2)C10—C9—C8117.8 (2)
C6—C1—C2120.0 (2)C10—C9—C13120.4 (2)
C1—C2—C7120.4 (2)C9—C10—H10120.0
C3—C2—C1117.1 (2)C9—C10—C11120.0 (2)
C3—C2—C7122.5 (2)C11—C10—H10120.0
C2—C3—Cl1119.9 (2)C10—C11—H11121.3
C2—C3—C4123.0 (2)C12—C11—C10117.4 (2)
C4—C3—Cl1117.0 (2)C12—C11—H11121.3
C3—C4—H4120.9N2—C12—C11125.4 (2)
C5—C4—C3118.3 (2)N2—C12—H12117.3
C5—C4—H4120.9C11—C12—H12117.3
C4—C5—H5119.0O1—C13—O2121.4 (2)
C4—C5—C6122.0 (2)O1—C13—C9126.6 (2)
C6—C5—H5119.0O2—C13—C9112.0 (2)
C1—C6—H6120.2O2—C14—H14A109.5
C5—C6—C1119.6 (3)O2—C14—H14B109.5
C5—C6—H6120.2O2—C14—H14C109.5
C2—C7—H7A109.5H14A—C14—H14B109.5
C2—C7—H7B109.5H14A—C14—H14C109.5
C2—C7—H7C109.5H14B—C14—H14C109.5
H7A—C7—H7B109.5
Cl1—C3—C4—C5180.0 (3)C7—C2—C3—Cl10.2 (4)
N1—C1—C2—C3179.5 (3)C7—C2—C3—C4179.6 (3)
N1—C1—C2—C70.0 (4)C8—N1—C1—C2176.7 (3)
N1—C1—C6—C5179.5 (3)C8—N1—C1—C63.5 (5)
N1—C8—C9—C10179.4 (3)C8—N2—C12—C110.2 (5)
N1—C8—C9—C130.8 (4)C8—C9—C10—C110.3 (4)
N2—C8—C9—C100.3 (4)C8—C9—C13—O13.2 (5)
N2—C8—C9—C13179.9 (3)C8—C9—C13—O2176.2 (3)
C1—N1—C8—N22.3 (5)C9—C10—C11—C120.1 (5)
C1—N1—C8—C9178.6 (3)C10—C9—C13—O1177.0 (3)
C1—C2—C3—Cl1179.7 (2)C10—C9—C13—O23.6 (4)
C1—C2—C3—C40.2 (4)C10—C11—C12—N20.1 (5)
C2—C1—C6—C50.3 (4)C12—N2—C8—N1179.2 (3)
C2—C3—C4—C50.1 (5)C12—N2—C8—C90.0 (4)
C3—C4—C5—C60.2 (5)C13—C9—C10—C11179.9 (3)
C4—C5—C6—C10.0 (5)C14—O2—C13—O10.6 (5)
C6—C1—C2—C30.3 (4)C14—O2—C13—C9180.0 (3)
C6—C1—C2—C7179.8 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O10.861.962.687 (3)142
C6—H6···N20.932.282.895 (4)123
 

Funding information

The authors thank the Natural Science Foundation of Hubei Province for financial support (2014CFB787).

References

First citationGupta, S. P. B. N. & Moorthy, N. S. H. N. (2007). Trends Appl. Sci. Res. 2, 165–169.  CAS Google Scholar
First citationBruker (2013). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationDolomanov, 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
First citationParsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259.  Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationVelingkar, V. S., Desai, D. M. & Panda, V. S. (2011). Int. J. Drug Des. Discov. 2, 548–558.  CAS Google Scholar

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