Ethyl 8-chloro-1-cyclo­propyl-6,7-difluoro-4-oxo-1,4-dihydro­quinoline-3-carboxyl­ate

Abstract

In the mol­ecule of the title compound, C₁₅H₁₂ClF₂NO₃, the quinoline ring system is not planar, the dihedral angle between the pyridine and benzene rings being 3.55 (8)°. In the crystal, inter­molecular C—H⋯O hydrogen bonds link the mol­ecules into layers parallel to (101).

Related literature

For the anti­bacterial activity of quinolone derivatives, see: Fujita & Chiba (1998 ▶). For a related structure, see: Wang et al. (2008 ▶).

Experimental

Crystal data

• C₁₅H₁₂ClF₂NO₃

• M _r = 327.71

• Monoclinic,

• a = 11.336 (2) Å

• b = 7.7440 (15) Å

• c = 16.157 (3) Å

• β = 95.40 (3)°

• V = 1412.1 (5) ų

• Z = 4

• Mo Kα radiation

• μ = 0.31 mm⁻¹

• T = 293 K

• 0.30 × 0.20 × 0.10 mm

Data collection

• Enraf–Nonius CAD-4 diffractometer

• Absorption correction: ψ scan (North et al., 1968 ▶) T _min = 0.914, T _max = 0.970

• 2741 measured reflections

• 2604 independent reflections

• 1728 reflections with I > 2σ(I)

• R _int = 0.025

• 3 standard reflections every 200 reflections intensity decay: 1%

Refinement

• R[F ² > 2σ(F ²)] = 0.053

• wR(F ²) = 0.158

• S = 1.00

• 2604 reflections

• 200 parameters

• H-atom parameters constrained

• Δρ_max = 0.21 e Å⁻³

• Δρ_min = −0.25 e Å⁻³

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994 ▶); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Supplementary material file. DOI: 10.1107/S160053681104205X/rz2646Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C11—H11A⋯O1i	0.97	2.55	3.240 (4)	128
C11—H11B⋯O1ii	0.97	2.54	3.491 (4)	167

Symmetry codes: (i) ; (ii) .

supplementary crystallographic information

Comment

Quinolone antibacterials were found several decades ago, and some excellent antibacterials have been developed and used widely (Fujita & Chiba, 1998). An interest in the search of more potent antibacterial agents led us to design and synthesize a new type of quinoline derivative. The title compound is one of the key intermediates and we report here its crystal structure.

The quinoline ring system is not planar, the dihedral angle between the pyridine and benzene rings being 3.55 (8)°. The dihedral angle between the three-membered ring and the quinoline ring system is 80.5 (5)°. Bond lengths and angles agree well with those observed in the strictly related compound ethyl 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate reported recently (Wang et al., 2008). In the crystal structure, intermolecular C—H···O hydrogen bonds link molecules into layers parallel to the (101) plane.

Experimental

A solution of 3-cyclopropylamino-2-(2,4,5-trifluoro-3-chlorobenzoyl)acrylic acid ethyl ester (26.1 g, 0.075 mol) in DMF (110 ml) was treated with K₂CO₃ (22 g, 0.16 mol) and then heated to 50°C with stirring for 1 h. The resulting precipitate was filtered, washed with a mixture of ice and water, and dried to give 22 g of the title compound (yield 90%). Crystals of the title compound suitable for X-ray diffraction analysis were obtained by slow evaporation of an acetone solution.

Refinement

All H atoms were positioned geometrically and refined using a riding model with C—H = 0.93–0.98 Å and U_iso(H) = 1.2 or 1.5 U_eq(C). A rotating-group model was applied for the methyl groups.

Figures

Fig. 1.

The molecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level.

Crystal data

C15H12ClF2NO3	F(000) = 672
Mr = 327.71	Dx = 1.541 Mg m−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 25 reflections
a = 11.336 (2) Å	θ = 9–13°
b = 7.7440 (15) Å	µ = 0.31 mm−1
c = 16.157 (3) Å	T = 293 K
β = 95.40 (3)°	Block, colourless
V = 1412.1 (5) Å3	0.30 × 0.20 × 0.10 mm
Z = 4

Data collection

Enraf–Nonius CAD-4 diffractometer	1728 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.025
graphite	θmax = 25.4°, θmin = 2.1°
ω/2θ scans	h = 0→13
Absorption correction: ψ scan (North et al., 1968)	k = 0→9
Tmin = 0.914, Tmax = 0.970	l = −19→19
2741 measured reflections	3 standard reflections every 200 reflections
2604 independent reflections	intensity decay: 1%

Refinement

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.053	H-atom parameters constrained
wR(F2) = 0.158	w = 1/[σ2(Fo2) + (0.094P)2] where P = (Fo2 + 2Fc2)/3
S = 1.00	(Δ/σ)max < 0.001
2604 reflections	Δρmax = 0.21 e Å−3
200 parameters	Δρmin = −0.25 e Å−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.022 (3)

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) 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
Cl	0.19669 (7)	0.51225 (11)	0.40024 (6)	0.0668 (4)
N	0.44922 (19)	0.3170 (3)	0.40949 (14)	0.0419 (6)
O1	0.59434 (19)	0.1055 (3)	0.62827 (13)	0.0642 (7)
C1	0.3696 (3)	0.2253 (4)	0.62119 (19)	0.0544 (8)
H1A	0.4037	0.1728	0.6694	0.065*
F1	0.19320 (19)	0.2766 (4)	0.68412 (14)	0.0983 (8)
O2	0.79506 (19)	0.0443 (3)	0.54403 (15)	0.0651 (7)
F2	0.09874 (16)	0.4358 (3)	0.54885 (14)	0.0800 (7)
C2	0.2582 (3)	0.2886 (5)	0.6180 (2)	0.0631 (9)
O3	0.79232 (18)	0.1827 (3)	0.42263 (14)	0.0627 (6)
C3	0.2086 (3)	0.3706 (4)	0.5476 (2)	0.0570 (9)
C4	0.2681 (3)	0.3882 (4)	0.47802 (19)	0.0485 (8)
C5	0.3828 (2)	0.3153 (3)	0.47746 (17)	0.0399 (7)
C6	0.4329 (2)	0.2392 (4)	0.55187 (17)	0.0420 (7)
C7	0.5626 (2)	0.2603 (4)	0.41917 (17)	0.0436 (7)
H7A	0.6060	0.2690	0.3733	0.052*
C8	0.6190 (2)	0.1915 (4)	0.48987 (17)	0.0421 (7)
C9	0.5555 (2)	0.1703 (4)	0.56176 (17)	0.0440 (7)
C10	0.4003 (3)	0.3598 (4)	0.32426 (17)	0.0499 (8)
H10A	0.3941	0.4831	0.3109	0.060*
C11	0.3070 (3)	0.2476 (4)	0.28256 (18)	0.0569 (9)
H11A	0.2816	0.1486	0.3131	0.068*
H11B	0.2450	0.3023	0.2462	0.068*
C12	0.4275 (3)	0.2441 (5)	0.25528 (18)	0.0630 (9)
H12A	0.4393	0.2967	0.2022	0.076*
H12B	0.4759	0.1431	0.2692	0.076*
C13	0.7432 (3)	0.1294 (4)	0.49057 (19)	0.0475 (7)
C14	0.9161 (3)	0.1308 (6)	0.4192 (2)	0.0697 (10)
H14A	0.9241	0.0067	0.4261	0.084*
H14B	0.9663	0.1869	0.4632	0.084*
C15	0.9506 (4)	0.1833 (6)	0.3377 (2)	0.0891 (13)
H15A	1.0316	0.1516	0.3332	0.134*
H15B	0.9421	0.3062	0.3317	0.134*
H15C	0.9005	0.1266	0.2947	0.134*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
Cl	0.0592 (5)	0.0603 (6)	0.0764 (6)	0.0187 (4)	−0.0166 (4)	−0.0001 (4)
N	0.0404 (13)	0.0399 (13)	0.0437 (13)	−0.0013 (10)	−0.0054 (10)	0.0007 (10)
O1	0.0579 (13)	0.0809 (17)	0.0511 (13)	0.0097 (12)	−0.0089 (10)	0.0147 (12)
C1	0.056 (2)	0.058 (2)	0.0477 (17)	−0.0018 (16)	0.0012 (15)	0.0002 (15)
F1	0.0732 (15)	0.146 (2)	0.0798 (14)	0.0125 (15)	0.0296 (12)	0.0032 (15)
O2	0.0507 (13)	0.0699 (16)	0.0727 (15)	0.0149 (11)	−0.0035 (12)	0.0137 (13)
F2	0.0461 (11)	0.0932 (16)	0.1010 (16)	0.0177 (11)	0.0077 (11)	−0.0139 (13)
C2	0.055 (2)	0.078 (2)	0.058 (2)	−0.0008 (18)	0.0145 (17)	−0.0068 (18)
O3	0.0421 (12)	0.0806 (17)	0.0646 (14)	0.0079 (11)	0.0012 (10)	0.0107 (13)
C3	0.0412 (17)	0.060 (2)	0.069 (2)	0.0050 (15)	0.0009 (16)	−0.0149 (18)
C4	0.0454 (17)	0.0388 (16)	0.0585 (19)	0.0015 (13)	−0.0102 (15)	−0.0070 (14)
C5	0.0364 (14)	0.0321 (14)	0.0493 (16)	−0.0045 (12)	−0.0057 (12)	−0.0023 (12)
C6	0.0423 (16)	0.0381 (15)	0.0440 (15)	−0.0032 (12)	−0.0039 (13)	−0.0028 (13)
C7	0.0408 (16)	0.0427 (16)	0.0470 (16)	−0.0042 (13)	0.0024 (13)	−0.0002 (14)
C8	0.0396 (15)	0.0378 (15)	0.0471 (16)	−0.0035 (12)	−0.0043 (13)	−0.0024 (13)
C9	0.0445 (16)	0.0395 (16)	0.0452 (17)	−0.0026 (13)	−0.0110 (13)	−0.0020 (14)
C10	0.0549 (18)	0.0459 (17)	0.0460 (17)	0.0000 (14)	−0.0102 (14)	0.0065 (14)
C11	0.055 (2)	0.061 (2)	0.0516 (17)	0.0007 (16)	−0.0129 (15)	0.0014 (16)
C12	0.069 (2)	0.076 (2)	0.0430 (17)	0.0012 (19)	0.0009 (16)	0.0032 (17)
C13	0.0442 (16)	0.0441 (17)	0.0526 (18)	−0.0020 (14)	−0.0044 (14)	−0.0023 (15)
C14	0.0433 (18)	0.087 (3)	0.079 (2)	0.0094 (18)	0.0044 (17)	0.005 (2)
C15	0.072 (3)	0.106 (3)	0.092 (3)	0.008 (2)	0.022 (2)	0.004 (3)

Geometric parameters (Å, °)

Cl—C4	1.723 (3)	C7—C8	1.364 (4)
N—C7	1.353 (3)	C7—H7A	0.9300
N—C5	1.389 (4)	C8—C9	1.432 (4)
N—C10	1.473 (3)	C8—C13	1.486 (4)
O1—C9	1.229 (3)	C10—C11	1.481 (4)
C1—C2	1.351 (5)	C10—C12	1.485 (4)
C1—C6	1.390 (4)	C10—H10A	0.9800
C1—H1A	0.9300	C11—C12	1.475 (5)
F1—C2	1.357 (4)	C11—H11A	0.9700
O2—C13	1.196 (3)	C11—H11B	0.9700
F2—C3	1.346 (4)	C12—H12A	0.9700
C2—C3	1.375 (5)	C12—H12B	0.9700
O3—C13	1.342 (4)	C14—C15	1.467 (5)
O3—C14	1.466 (4)	C14—H14A	0.9700
C3—C4	1.371 (4)	C14—H14B	0.9700
C4—C5	1.418 (4)	C15—H15A	0.9600
C5—C6	1.410 (4)	C15—H15B	0.9600
C6—C9	1.483 (4)	C15—H15C	0.9600
C7—N—C5	119.0 (2)	N—C10—C12	118.7 (3)
C7—N—C10	116.8 (2)	C11—C10—C12	59.6 (2)
C5—N—C10	123.8 (2)	N—C10—H10A	116.0
C2—C1—C6	119.5 (3)	C11—C10—H10A	116.0
C2—C1—H1A	120.3	C12—C10—H10A	116.0
C6—C1—H1A	120.3	C12—C11—C10	60.3 (2)
C1—C2—F1	121.3 (3)	C12—C11—H11A	117.7
C1—C2—C3	120.5 (3)	C10—C11—H11A	117.7
F1—C2—C3	118.2 (3)	C12—C11—H11B	117.7
C13—O3—C14	114.8 (2)	C10—C11—H11B	117.7
F2—C3—C4	120.2 (3)	H11A—C11—H11B	114.9
F2—C3—C2	117.9 (3)	C11—C12—C10	60.1 (2)
C4—C3—C2	121.9 (3)	C11—C12—H12A	117.8
C3—C4—C5	119.2 (3)	C10—C12—H12A	117.8
C3—C4—Cl	114.8 (2)	C11—C12—H12B	117.8
C5—C4—Cl	125.9 (3)	C10—C12—H12B	117.8
N—C5—C6	118.3 (2)	H12A—C12—H12B	114.9
N—C5—C4	124.5 (3)	O2—C13—O3	123.1 (3)
C6—C5—C4	117.2 (3)	O2—C13—C8	125.8 (3)
C1—C6—C5	121.5 (3)	O3—C13—C8	111.1 (3)
C1—C6—C9	115.8 (3)	O3—C14—C15	107.1 (3)
C5—C6—C9	122.7 (3)	O3—C14—H14A	110.3
N—C7—C8	126.1 (3)	C15—C14—H14A	110.3
N—C7—H7A	116.9	O3—C14—H14B	110.3
C8—C7—H7A	116.9	C15—C14—H14B	110.3
C7—C8—C9	119.4 (3)	H14A—C14—H14B	108.5
C7—C8—C13	120.1 (3)	C14—C15—H15A	109.5
C9—C8—C13	120.3 (3)	C14—C15—H15B	109.5
O1—C9—C8	126.1 (3)	H15A—C15—H15B	109.5
O1—C9—C6	119.7 (3)	C14—C15—H15C	109.5
C8—C9—C6	114.2 (2)	H15A—C15—H15C	109.5
N—C10—C11	118.9 (3)	H15B—C15—H15C	109.5
C6—C1—C2—F1	179.6 (3)	C10—N—C7—C8	−170.2 (3)
C6—C1—C2—C3	−1.8 (5)	N—C7—C8—C9	1.7 (4)
C1—C2—C3—F2	−178.0 (3)	N—C7—C8—C13	178.1 (3)
F1—C2—C3—F2	0.7 (5)	C7—C8—C9—O1	177.6 (3)
C1—C2—C3—C4	1.4 (5)	C13—C8—C9—O1	1.3 (5)
F1—C2—C3—C4	−179.9 (3)	C7—C8—C9—C6	−3.9 (4)
F2—C3—C4—C5	−178.7 (3)	C13—C8—C9—C6	179.8 (2)
C2—C3—C4—C5	2.0 (5)	C1—C6—C9—O1	0.3 (4)
F2—C3—C4—Cl	5.2 (4)	C5—C6—C9—O1	179.9 (3)
C2—C3—C4—Cl	−174.1 (3)	C1—C6—C9—C8	−178.3 (2)
C7—N—C5—C6	−5.9 (4)	C5—C6—C9—C8	1.3 (4)
C10—N—C5—C6	167.3 (2)	C7—N—C10—C11	110.6 (3)
C7—N—C5—C4	172.8 (3)	C5—N—C10—C11	−62.8 (4)
C10—N—C5—C4	−13.9 (4)	C7—N—C10—C12	41.4 (4)
C3—C4—C5—N	176.6 (3)	C5—N—C10—C12	−132.0 (3)
Cl—C4—C5—N	−7.8 (4)	N—C10—C11—C12	−108.2 (3)
C3—C4—C5—C6	−4.7 (4)	N—C10—C12—C11	108.5 (3)
Cl—C4—C5—C6	170.9 (2)	C14—O3—C13—O2	−0.9 (5)
C2—C1—C6—C5	−1.1 (5)	C14—O3—C13—C8	178.5 (3)
C2—C1—C6—C9	178.4 (3)	C7—C8—C13—O2	−168.0 (3)
N—C5—C6—C1	−176.8 (3)	C9—C8—C13—O2	8.3 (5)
C4—C5—C6—C1	4.3 (4)	C7—C8—C13—O3	12.5 (4)
N—C5—C6—C9	3.6 (4)	C9—C8—C13—O3	−171.2 (2)
C4—C5—C6—C9	−175.2 (3)	C13—O3—C14—C15	174.0 (3)
C5—N—C7—C8	3.5 (4)

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
C11—H11A···O1i	0.97	2.55	3.240 (4)	128.
C11—H11B···O1ii	0.97	2.54	3.491 (4)	167.

Symmetry codes: (i) −x+1, −y, −z+1; (ii) x−1/2, −y+1/2, z−1/2.