Crystal structure of ethyl 2-(3,5-di­fluoro­phen­yl)quinoline-4-carboxyl­ate

In the title compound, C₁₈H₁₃F₂NO₂, the two rings of the quinoline system are fused almost coaxially, with a dihedral angle between their planes of 2.28 (8)°. The plane of the attached benzene ring is inclined to the plane of the quinoline system by 7.65 (7)°. The carboxyl­ate group attached to the quinoline system is in an anti­periplanar conformation. There is a short intra­molecular C—H...O contact involving the carbonyl group. In the crystal, mol­ecules are linked via C—H...O hydrogen bonds, forming chains lying in the (1-10) plane.

Key indicators

• Single-crystal X-ray study
• T = 296 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.044
• wR factor = 0.131
• Data-to-parameter ratio = 11.8

checkCIF/PLATON results

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Alert level C
THETM01_ALERT_3_C  The value of sine(theta_max)/wavelength is less than 0.590
            Calculated sin(theta_max)/wavelength =    0.5850
PLAT029_ALERT_3_C _diffrn_measured_fraction_theta_full Low .......      0.979 Note
PLAT334_ALERT_2_C Small Average Benzene  C-C Dist. C11    -C16           1.37 Ang.
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.585         48 Report
PLAT913_ALERT_3_C Missing # of Very Strong Reflections in FCF ....          7 Note

Alert level G
PLAT005_ALERT_5_G No _iucr_refine_instructions_details  in the CIF     Please Do !
PLAT066_ALERT_1_G Predicted and Reported Tmin&Tmax Range Identical          ? Check
PLAT154_ALERT_1_G The su's on the Cell Angles are Equal ..........    0.00200 Degree
PLAT909_ALERT_3_G Percentage of Observed Data at Theta(Max) still          64 %
PLAT910_ALERT_3_G Missing # of FCF Reflection(s) Below Th(Min) ...          4 Report

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
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   2 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
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PUBL024_ALERT_1_A The number of authors is greater than 5.
              Please specify the role of each of the co-authors
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Author Response: ... All the authors have equal contribution to this work SVM -- Synthesis NS -- Data Collection and Processing HRM -- Structure solution and corresponding author BSP -- Crystallization MV -- Data analysis NKL -- Principal Investigator

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---

S1. Comment

Quinoline derivatives are well known for their wide range of biological and pharmaceutical activities and are prevalent in pharmacologically active natural and synthetic compounds. Quinoline-4-carboxyl­ates are potential 5HT₃ antagonizer and also they possess anti-emetic activity. In view of their broad spectrum of medicinal properties and in continuation of our work on new quinoline-based therapeutic agents (Pradeep et al., 2014, Shrungesh Kumar et al., 2015), we have synthesized the title compound and report herein on its crystal structure.

The structure of the compound is shown in Fig. 1. The dihedral angle between the benzene ring and the quinoline ring system is 7.65 (7) °. The carboxyl­ate group attached to the quinoline moiety is in an -anti periplanar conformation which is evident by the torsion angle C22—O21—C19—C8 = -176.71 (15)°. The two rings of the quinoline moiety are fused in an axial fashion with a dihedral angle value of 2.28 (8)°. The deviation of the bond length values for C8—C19 and C10—C11 from the standard values can be attributed for the sp³ hybridization.

In the crystal, molecules are linked via C—H···O hydrogen bonds forming chains lying in the (110) plane. (Fig. 2 and Table 1).

S2. Synthesis and crystallization

To a solution of 2-(3,5-di­fluoro­phenyl)­quinoline-4-carb­oxy­lic acid (0.5 g) in 20 ml of EtOH, 1 ml of H₂SO₄ (conc.) was added. The resulting reaction mixture was refluxed for 15 h. Solvent was removed under reduced pressure and the residue was partitioned between EtOAc and saturated NaHCO₃ solution. The organic layer was washed with water and brine, dried over anhydrous Na₂SO₄, filtered, and condensed to give the title compound as a white solid (yield: 93%). The compound was dissolved in di­methyl­formamide and the solution was gently heated and left undisturbed. Brown, re­cta­ngular crystals grew after 12 days by slow evaporation of the solvent.

S3. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. All the H atoms were fixed geometrically (C—H= 0.93–0.96 Å) and allowed to ride on their parent atoms with U_iso(H) = 1.5U_eq(C) for methyl H atoms and 1.2U_eq(C) for other H atoms.

Related literature

For the crystal structures of related quinoline derivatives, see: Pradeep et al. (2014); Shrungesh Kumar et al. (2015).

Structure description

Quinoline derivatives are well known for their wide range of biological and pharmaceutical activities and are prevalent in pharmacologically active natural and synthetic compounds. Quinoline-4-carboxyl­ates are potential 5HT₃ antagonizer and also they possess anti-emetic activity. In view of their broad spectrum of medicinal properties and in continuation of our work on new quinoline-based therapeutic agents (Pradeep et al., 2014, Shrungesh Kumar et al., 2015), we have synthesized the title compound and report herein on its crystal structure.

The structure of the compound is shown in Fig. 1. The dihedral angle between the benzene ring and the quinoline ring system is 7.65 (7) °. The carboxyl­ate group attached to the quinoline moiety is in an -anti periplanar conformation which is evident by the torsion angle C22—O21—C19—C8 = -176.71 (15)°. The two rings of the quinoline moiety are fused in an axial fashion with a dihedral angle value of 2.28 (8)°. The deviation of the bond length values for C8—C19 and C10—C11 from the standard values can be attributed for the sp³ hybridization.

In the crystal, molecules are linked via C—H···O hydrogen bonds forming chains lying in the (110) plane. (Fig. 2 and Table 1).

For the crystal structures of related quinoline derivatives, see: Pradeep et al. (2014); Shrungesh Kumar et al. (2015).

Synthesis and crystallization

To a solution of 2-(3,5-di­fluoro­phenyl)­quinoline-4-carb­oxy­lic acid (0.5 g) in 20 ml of EtOH, 1 ml of H₂SO₄ (conc.) was added. The resulting reaction mixture was refluxed for 15 h. Solvent was removed under reduced pressure and the residue was partitioned between EtOAc and saturated NaHCO₃ solution. The organic layer was washed with water and brine, dried over anhydrous Na₂SO₄, filtered, and condensed to give the title compound as a white solid (yield: 93%). The compound was dissolved in di­methyl­formamide and the solution was gently heated and left undisturbed. Brown, re­cta­ngular crystals grew after 12 days by slow evaporation of the solvent.

Refinement details

Crystal data, data collection and structure refinement details are summarized in Table 2. All the H atoms were fixed geometrically (C—H= 0.93–0.96 Å) and allowed to ride on their parent atoms with U_iso(H) = 1.5U_eq(C) for methyl H atoms and 1.2U_eq(C) for other H atoms.

Computing details

Data collection: APEX2 (Bruker, 2013); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures

	Fig. 1. View of the molecular structure of the title compound, with atom labelling. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. A view along the a axis of the crystal packing of the title compound. Hydrogen bonds are shown as dashed lines (see Table 1 for details).

Ethyl 2-(3,5-difluorophenyl)quinoline-4-carboxylate

Crystal data

C18H13F2NO2	Z = 2
Mr = 313.29	F(000) = 324
Triclinic, P1	Dx = 1.376 Mg m^−3
Hall symbol: -P 1	Cu Kα radiation, λ = 1.54178 Å
a = 8.2674 (3) Å	Cell parameters from 2482 reflections
b = 10.0529 (4) Å	θ = 6.1–64.4°
c = 10.0562 (4) Å	µ = 0.90 mm^−1
α = 101.193 (2)°	T = 296 K
β = 108.616 (2)°	Rectangle, brown
γ = 98.741 (2)°	0.30 × 0.27 × 0.25 mm
V = 756.14 (5) Å^3

Data collection

Bruker X8 Proteum diffractometer	2482 independent reflections
Radiation source: Bruker MicroStar microfocus rotating anode	2147 reflections with I > 2σ(I)
Helios multilayer optics monochromator	Rint = 0.038
Detector resolution: 10.7 pixels mm^-1	θmax = 64.4°, θmin = 6.1°
φ and ω scans	h = −9→9
Absorption correction: multi-scan (SADABS; Bruker, 2013)	k = −11→11
Tmin = 0.763, Tmax = 0.799	l = −11→11
9032 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.044	H-atom parameters constrained
wR(F^2) = 0.131	w = 1/[σ^2(Fo^2) + (0.0696P)^2 + 0.099P] where P = (Fo^2 + 2Fc^2)/3
S = 1.05	(Δ/σ)max < 0.001
2482 reflections	Δρmax = 0.16 e Å^−3
210 parameters	Δρmin = −0.22 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), FC^* = KFC[1+0.001XFC^2Λ^3/SIN(2Θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.011 (3)

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F² for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating -R-factor-obs etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
F17	−0.07505 (13)	0.11215 (10)	0.69978 (11)	0.0832 (4)
F18	−0.21878 (16)	0.10400 (12)	0.20982 (12)	0.0993 (4)
O20	0.5498 (2)	0.83249 (15)	0.42261 (16)	0.1012 (6)
O21	0.31565 (15)	0.67459 (11)	0.26915 (12)	0.0665 (4)
N1	0.35974 (15)	0.51312 (12)	0.70955 (13)	0.0525 (4)
C2	0.48895 (19)	0.63200 (14)	0.75527 (16)	0.0520 (4)
C3	0.5941 (2)	0.67423 (17)	0.90376 (18)	0.0698 (6)
C4	0.7210 (3)	0.7948 (2)	0.9594 (2)	0.0830 (7)
C5	0.7486 (3)	0.87609 (19)	0.8681 (2)	0.0837 (7)
C6	0.6535 (2)	0.83789 (16)	0.72399 (19)	0.0682 (6)
C7	0.51962 (18)	0.71364 (14)	0.66138 (16)	0.0512 (5)
C8	0.41001 (18)	0.66272 (14)	0.51179 (16)	0.0477 (4)
C9	0.28096 (18)	0.54385 (14)	0.46942 (15)	0.0475 (4)
C10	0.25718 (17)	0.47149 (13)	0.57158 (15)	0.0458 (4)
C11	0.11409 (17)	0.34387 (13)	0.52808 (15)	0.0473 (4)
C12	0.0105 (2)	0.28135 (15)	0.38426 (17)	0.0578 (5)
C13	−0.1193 (2)	0.16400 (16)	0.35114 (17)	0.0622 (5)
C14	−0.1529 (2)	0.10394 (15)	0.45354 (19)	0.0610 (5)
C15	−0.0474 (2)	0.16870 (15)	0.59420 (18)	0.0577 (5)
C16	0.08370 (19)	0.28567 (15)	0.63472 (17)	0.0544 (5)
C19	0.4343 (2)	0.73427 (15)	0.39981 (18)	0.0573 (5)
C22	0.3365 (3)	0.7336 (2)	0.1529 (2)	0.0850 (8)
C23	0.1898 (4)	0.6564 (3)	0.0175 (3)	0.1138 (10)
H3	0.57680	0.61930	0.96470	0.0840*
H4	0.78890	0.82250	1.05790	0.1000*
H5	0.83450	0.95880	0.90700	0.1000*
H6	0.67630	0.89370	0.66540	0.0820*
H9	0.20810	0.51030	0.37230	0.0570*
H12	0.02840	0.31830	0.31080	0.0690*
H14	−0.24150	0.02450	0.42900	0.0730*
H16	0.15150	0.32560	0.73220	0.0650*
H22A	0.44750	0.72490	0.14270	0.1020*
H22B	0.33500	0.83160	0.17440	0.1020*
H23A	0.18670	0.55860	0.00140	0.1710*
H23B	0.20580	0.68790	−0.06260	0.1710*
H23C	0.08140	0.67240	0.02550	0.1710*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
F17	0.0858 (7)	0.0796 (7)	0.0865 (7)	−0.0067 (5)	0.0321 (6)	0.0446 (5)
F18	0.1077 (9)	0.0813 (7)	0.0655 (7)	−0.0309 (6)	0.0073 (6)	0.0027 (5)
O20	0.1060 (11)	0.0881 (9)	0.0877 (10)	−0.0363 (8)	0.0244 (8)	0.0372 (7)
O21	0.0731 (7)	0.0690 (7)	0.0589 (7)	0.0017 (5)	0.0253 (6)	0.0284 (5)
N1	0.0544 (7)	0.0478 (7)	0.0520 (7)	0.0038 (5)	0.0171 (6)	0.0154 (5)
C2	0.0507 (8)	0.0465 (7)	0.0545 (8)	0.0059 (6)	0.0162 (7)	0.0122 (6)
C3	0.0755 (11)	0.0633 (10)	0.0568 (9)	0.0024 (8)	0.0119 (8)	0.0151 (7)
C4	0.0820 (12)	0.0736 (11)	0.0620 (11)	−0.0057 (9)	0.0003 (9)	0.0091 (9)
C5	0.0757 (12)	0.0615 (10)	0.0820 (13)	−0.0157 (8)	0.0065 (10)	0.0086 (9)
C6	0.0654 (10)	0.0546 (9)	0.0720 (11)	−0.0056 (7)	0.0173 (8)	0.0156 (8)
C7	0.0478 (8)	0.0445 (7)	0.0587 (9)	0.0066 (6)	0.0186 (7)	0.0118 (6)
C8	0.0463 (7)	0.0436 (7)	0.0572 (8)	0.0086 (6)	0.0225 (6)	0.0168 (6)
C9	0.0464 (7)	0.0455 (7)	0.0497 (8)	0.0064 (6)	0.0166 (6)	0.0145 (6)
C10	0.0452 (7)	0.0428 (7)	0.0503 (8)	0.0082 (6)	0.0178 (6)	0.0145 (6)
C11	0.0454 (7)	0.0431 (7)	0.0547 (8)	0.0080 (6)	0.0187 (6)	0.0163 (6)
C12	0.0628 (9)	0.0505 (8)	0.0564 (9)	0.0002 (7)	0.0208 (7)	0.0169 (7)
C13	0.0615 (9)	0.0513 (8)	0.0595 (9)	−0.0003 (7)	0.0129 (7)	0.0079 (7)
C14	0.0540 (9)	0.0432 (8)	0.0819 (11)	0.0004 (6)	0.0227 (8)	0.0185 (7)
C15	0.0561 (9)	0.0513 (8)	0.0731 (10)	0.0075 (6)	0.0270 (8)	0.0303 (7)
C16	0.0525 (8)	0.0534 (8)	0.0567 (9)	0.0053 (6)	0.0175 (7)	0.0217 (7)
C19	0.0578 (9)	0.0518 (8)	0.0661 (10)	0.0065 (7)	0.0258 (8)	0.0227 (7)
C22	0.0999 (14)	0.0970 (14)	0.0718 (12)	0.0123 (11)	0.0406 (11)	0.0442 (10)
C23	0.1130 (18)	0.156 (2)	0.0710 (13)	0.0141 (16)	0.0238 (12)	0.0552 (14)

Geometric parameters (Å, º)

F17—C15	1.3611 (19)	C11—C16	1.388 (2)
F18—C13	1.3528 (19)	C12—C13	1.374 (2)
O20—C19	1.194 (2)	C13—C14	1.369 (2)
O21—C19	1.319 (2)	C14—C15	1.367 (2)
O21—C22	1.454 (2)	C15—C16	1.367 (2)
N1—C2	1.366 (2)	C22—C23	1.475 (4)
N1—C10	1.3171 (18)	C3—H3	0.9300
C2—C3	1.407 (2)	C4—H4	0.9300
C2—C7	1.421 (2)	C5—H5	0.9300
C3—C4	1.363 (3)	C6—H6	0.9300
C4—C5	1.390 (3)	C9—H9	0.9300
C5—C6	1.353 (3)	C12—H12	0.9300
C6—C7	1.418 (2)	C14—H14	0.9300
C7—C8	1.427 (2)	C16—H16	0.9300
C8—C9	1.368 (2)	C22—H22A	0.9700
C8—C19	1.497 (2)	C22—H22B	0.9700
C9—C10	1.414 (2)	C23—H23A	0.9600
C10—C11	1.492 (2)	C23—H23B	0.9600
C11—C12	1.383 (2)	C23—H23C	0.9600
C19—O21—C22	115.85 (14)	O20—C19—O21	122.45 (16)
C2—N1—C10	118.74 (12)	O20—C19—C8	124.87 (16)
N1—C2—C3	117.08 (14)	O21—C19—C8	112.65 (14)
N1—C2—C7	123.41 (13)	O21—C22—C23	107.77 (19)
C3—C2—C7	119.51 (14)	C2—C3—H3	120.00
C2—C3—C4	120.79 (16)	C4—C3—H3	120.00
C3—C4—C5	119.67 (17)	C3—C4—H4	120.00
C4—C5—C6	121.59 (19)	C5—C4—H4	120.00
C5—C6—C7	120.72 (16)	C4—C5—H5	119.00
C2—C7—C6	117.68 (14)	C6—C5—H5	119.00
C2—C7—C8	116.27 (13)	C5—C6—H6	120.00
C6—C7—C8	126.04 (14)	C7—C6—H6	120.00
C7—C8—C9	118.95 (13)	C8—C9—H9	120.00
C7—C8—C19	121.86 (13)	C10—C9—H9	120.00
C9—C8—C19	119.19 (13)	C11—C12—H12	120.00
C8—C9—C10	120.74 (13)	C13—C12—H12	120.00
N1—C10—C9	121.83 (13)	C13—C14—H14	122.00
N1—C10—C11	116.69 (12)	C15—C14—H14	122.00
C9—C10—C11	121.48 (12)	C11—C16—H16	121.00
C10—C11—C12	121.97 (13)	C15—C16—H16	121.00
C10—C11—C16	119.24 (13)	O21—C22—H22A	110.00
C12—C11—C16	118.79 (14)	O21—C22—H22B	110.00
C11—C12—C13	119.22 (14)	C23—C22—H22A	110.00
F18—C13—C12	118.35 (14)	C23—C22—H22B	110.00
F18—C13—C14	118.13 (15)	H22A—C22—H22B	108.00
C12—C13—C14	123.52 (15)	C22—C23—H23A	109.00
C13—C14—C15	115.41 (15)	C22—C23—H23B	109.00
F17—C15—C14	117.53 (14)	C22—C23—H23C	110.00
F17—C15—C16	118.38 (14)	H23A—C23—H23B	109.00
C14—C15—C16	124.09 (15)	H23A—C23—H23C	109.00
C11—C16—C15	118.97 (14)	H23B—C23—H23C	109.00
C19—O21—C22—C23	−178.32 (19)	C19—C8—C9—C10	178.34 (14)
C22—O21—C19—O20	1.5 (3)	C9—C8—C19—O21	3.7 (2)
C22—O21—C19—C8	−176.71 (15)	C7—C8—C19—O20	4.4 (3)
C10—N1—C2—C7	−0.3 (2)	C7—C8—C19—O21	−177.37 (14)
C10—N1—C2—C3	179.08 (15)	C9—C8—C19—O20	−174.49 (18)
C2—N1—C10—C9	2.1 (2)	C8—C9—C10—N1	−1.7 (2)
C2—N1—C10—C11	−177.91 (13)	C8—C9—C10—C11	178.32 (14)
N1—C2—C3—C4	−177.18 (18)	N1—C10—C11—C12	−172.73 (14)
C3—C2—C7—C6	−1.9 (2)	C9—C10—C11—C16	−172.80 (14)
C3—C2—C7—C8	178.80 (15)	N1—C10—C11—C16	7.2 (2)
N1—C2—C7—C6	177.45 (15)	C9—C10—C11—C12	7.3 (2)
N1—C2—C7—C8	−1.9 (2)	C16—C11—C12—C13	0.1 (2)
C7—C2—C3—C4	2.2 (3)	C10—C11—C12—C13	−179.96 (16)
C2—C3—C4—C5	−0.9 (3)	C10—C11—C16—C15	−179.93 (15)
C3—C4—C5—C6	−0.7 (4)	C12—C11—C16—C15	0.0 (2)
C4—C5—C6—C7	1.0 (3)	C11—C12—C13—F18	−179.73 (15)
C5—C6—C7—C2	0.3 (3)	C11—C12—C13—C14	−0.1 (3)
C5—C6—C7—C8	179.57 (18)	C12—C13—C14—C15	−0.1 (3)
C6—C7—C8—C9	−177.03 (16)	F18—C13—C14—C15	179.58 (15)
C2—C7—C8—C19	−176.71 (14)	C13—C14—C15—F17	−179.53 (15)
C2—C7—C8—C9	2.2 (2)	C13—C14—C15—C16	0.2 (3)
C6—C7—C8—C19	4.0 (3)	F17—C15—C16—C11	179.57 (14)
C7—C8—C9—C10	−0.6 (2)	C14—C15—C16—C11	−0.2 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C6—H6···O20	0.93	2.24	2.861 (2)	123
C14—H14···O20^i	0.93	2.36	3.275 (2)	167

Symmetry code: (i) x−1, y−1, z.