1-Ethyl-6-fluoro-7-(4-formyl­piperazin-1-yl)-4-oxo-1,4-dihydro­quinoline-3-carboxylic acid

Lou, B.; Boström, D.; Velaga, S.P.

doi:10.1107/S1600536807048726

1-Ethyl-6-fluoro-7-(4-formylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

The formylation reaction of norfloxacin with N,N-dimethylformamide (DMF) gives the title compound, C₁₇H₁₈FN₃O₄. In the structure, molecules are connected via weak C—H

O, C—H

π and π–π interactions [perpendicular distance 3.423 Å and centroid–centroid distance 3.8141 Å].

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807048726/nc2060sup1.cif Contains datablocks I, global
	Structure factor file (CIF format) https://doi.org/10.1107/S1600536807048726/nc2060Isup2.hkl Contains datablock I

CCDC reference: 667327

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Key indicators

Single-crystal X-ray study
T = 150 K
Mean (C-C) = 0.002 Å
R factor = 0.043
wR factor = 0.123
Data-to-parameter ratio = 16.0

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No syntax errors found



Alert level C
PLAT154_ALERT_1_C The su's on the Cell Angles are Equal  (x 10000)       3000 Deg.

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   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
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Comment top

Norfloxacin (1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3- quinolinecarboxylic acid) is a widely used fluoroquinolone antibacterial compound (Holmes et al., 1985). For this compound, polymorphs, salts and cocrystals have been widely studied (Barbas et al., 2006; Basavoju et al., 2006). In this paper, we report the title compound (I), a derivative of norfloxacin.

The molecular structure of compound (I) (Fig.1) is similar with that of formylated ciprofloxacin reported previously (Li et al., 2005). The piperazinyl ring adopts a chair conformation and the carboxylic group is involved in intramolecular hydrogen bonding with the quinolone oxygen atom (O2—H2···O3, see Table. 1).

In the crystal structure the molecules are connected via weak C—H···O interactions (Fig.2 and Table. 2). Additionally weak π-π interactions between quinolone rings and C—H···π interactions between piperazinyl ring and quinolone ring might exist (Table. 2).

Related literature top

For related literature, see: Barbas et al. (2006); Basavoju et al. (2006); Holmes et al. (1985); Li et al. (2005).

Experimental top

A mixture of norfloxacin (0.032 g, 0.1 mmol) and phosphoric acid (0.020 g, 0.2 mmol) was dissolved in DMF (10 ml) by heating. Afterwards, the solution was kept in air and after several days yellow crystals were obtained. The DSC showed one sharp endothermic peak at 562 K attributed to the melting transition.

Structure description top

For related literature, see: Barbas et al. (2006); Basavoju et al. (2006); Holmes et al. (1985); Li et al. (2005).

Computing details top

Data collection: COLLECT (Nonius, 1999); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: SCALEPACK/DENZO (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: X-SEED (Barbour, 2001); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997).

Figures top

	Fig. 1. ORTEP plot of compound (I) with 30% thermal ellipsoids. The dashed line indicate hydrogen bonding.
	Fig. 2. Packing diagram of compound (I) viewed along b axis. The dashed lines indicate C—H···O interactions.

1-Ethyl-6-fluoro-7-(4-formylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline- 3-carboxylic acid top

Crystal data top

C₁₇H₁₈FN₃O₄	Z = 2
M_r = 347.34	F(000) = 364
Triclinic, P1	D_x = 1.432 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 8.6689 (17) Å	Cell parameters from 7249 reflections
b = 9.6727 (19) Å	θ = 2.6–27.5°
c = 10.142 (2) Å	µ = 0.11 mm⁻¹
α = 73.41 (3)°	T = 150 K
β = 81.41 (3)°	Block, yellow
γ = 86.48 (3)°	0.24 × 0.20 × 0.16 mm
V = 805.8 (3) Å³

Data collection top

Nonius KappaCCD diffractometer	2913 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.020
Graphite monochromator	θ_max = 27.4°, θ_min = 3.2°
Detector resolution: 9 pixels mm^-1	h = −11→11
CCD scans	k = −11→12
6043 measured reflections	l = −13→13
3635 independent reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.043	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.123	H-atom parameters constrained
S = 1.05	w = 1/[σ²(F_o²) + (0.0613P)² + 0.2204P] where P = (F_o² + 2F_c²)/3
3635 reflections	(Δ/σ)_max < 0.001
227 parameters	Δρ_max = 0.21 e Å⁻³
0 restraints	Δρ_min = −0.25 e Å⁻³

Crystal data top

C₁₇H₁₈FN₃O₄	γ = 86.48 (3)°
M_r = 347.34	V = 805.8 (3) Å³
Triclinic, P1	Z = 2
a = 8.6689 (17) Å	Mo Kα radiation
b = 9.6727 (19) Å	µ = 0.11 mm⁻¹
c = 10.142 (2) Å	T = 150 K
α = 73.41 (3)°	0.24 × 0.20 × 0.16 mm
β = 81.41 (3)°

Data collection top

Nonius KappaCCD diffractometer	2913 reflections with I > 2σ(I)
6043 measured reflections	R_int = 0.020
3635 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.043	0 restraints
wR(F²) = 0.123	H-atom parameters constrained
S = 1.05	Δρ_max = 0.21 e Å⁻³
3635 reflections	Δρ_min = −0.25 e Å⁻³
227 parameters

Special details top

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 (Å²) top

	x	y	z	U_iso*/U_eq
F1	0.10241 (9)	0.66737 (10)	1.00486 (9)	0.0311 (2)
O3	0.45388 (12)	0.85673 (12)	1.26189 (11)	0.0311 (3)
O1	0.91842 (14)	0.96327 (14)	1.19206 (12)	0.0404 (3)
N3	0.72533 (13)	0.81858 (12)	0.90353 (12)	0.0212 (2)
C2	0.69908 (16)	0.88460 (14)	1.11704 (14)	0.0216 (3)
O2	0.68961 (14)	0.94959 (13)	1.32791 (11)	0.0342 (3)
H2	0.5985	0.9248	1.3277	0.041*
C10	0.50281 (15)	0.72728 (15)	0.83179 (14)	0.0215 (3)
H10	0.5663	0.7181	0.7498	0.026*
C6	0.47421 (15)	0.79129 (14)	1.05125 (13)	0.0204 (3)
C5	0.56759 (15)	0.77973 (14)	0.92778 (13)	0.0199 (3)
C7	0.31595 (16)	0.75016 (15)	1.07694 (14)	0.0233 (3)
H7	0.2517	0.7564	1.1596	0.028*
N2	0.27120 (13)	0.64380 (13)	0.76203 (11)	0.0220 (3)
C3	0.53768 (16)	0.84585 (14)	1.15125 (14)	0.0220 (3)
C9	0.34614 (15)	0.68881 (14)	0.85666 (14)	0.0208 (3)
C8	0.25720 (15)	0.70150 (15)	0.98143 (14)	0.0229 (3)
C1	0.77959 (18)	0.93698 (16)	1.21315 (15)	0.0272 (3)
C16	0.10726 (16)	0.46445 (15)	0.72264 (14)	0.0238 (3)
H16A	0.0806	0.3610	0.7525	0.029*
H16B	0.0098	0.5216	0.7329	0.029*
C4	0.78423 (16)	0.86968 (14)	0.99515 (14)	0.0226 (3)
H4	0.8904	0.8971	0.9750	0.027*
C13	0.35023 (17)	0.67645 (17)	0.61811 (14)	0.0274 (3)
H13A	0.4439	0.6133	0.6131	0.033*
H13B	0.3839	0.7780	0.5861	0.033*
C11	0.83052 (15)	0.80245 (16)	0.77815 (15)	0.0259 (3)
H11A	0.8088	0.7100	0.7615	0.031*
H11B	0.9401	0.7982	0.7962	0.031*
C14	0.23709 (18)	0.65157 (17)	0.52533 (15)	0.0296 (3)
H14A	0.1485	0.7214	0.5236	0.036*
H14B	0.2911	0.6673	0.4292	0.036*
C15	0.22025 (16)	0.49259 (15)	0.81329 (14)	0.0243 (3)
H15A	0.1685	0.4732	0.9105	0.029*
H15B	0.3122	0.4268	0.8117	0.029*
C12	0.81170 (18)	0.92472 (19)	0.64838 (15)	0.0330 (4)
H12A	0.7042	0.9279	0.6282	0.050*
H12B	0.8838	0.9087	0.5698	0.050*
H12C	0.8349	1.0165	0.6634	0.050*
O4	0.25308 (14)	0.44029 (14)	0.37679 (12)	0.0406 (3)
N1	0.17883 (14)	0.50451 (13)	0.57763 (12)	0.0256 (3)
C17	0.19313 (17)	0.41258 (17)	0.49896 (16)	0.0294 (3)
H17	0.1537	0.3184	0.5412	0.035*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0184 (4)	0.0461 (5)	0.0299 (5)	−0.0092 (4)	0.0009 (3)	−0.0130 (4)
O3	0.0297 (5)	0.0413 (6)	0.0251 (5)	−0.0075 (5)	0.0026 (4)	−0.0155 (5)
O1	0.0342 (6)	0.0570 (8)	0.0371 (6)	−0.0161 (5)	−0.0073 (5)	−0.0199 (6)
N3	0.0181 (5)	0.0254 (6)	0.0211 (5)	−0.0023 (4)	−0.0024 (4)	−0.0077 (4)
C2	0.0241 (7)	0.0191 (6)	0.0222 (6)	−0.0022 (5)	−0.0058 (5)	−0.0052 (5)
O2	0.0379 (6)	0.0423 (6)	0.0280 (6)	−0.0089 (5)	−0.0049 (5)	−0.0168 (5)
C10	0.0196 (6)	0.0243 (7)	0.0204 (6)	−0.0029 (5)	−0.0016 (5)	−0.0061 (5)
C6	0.0211 (6)	0.0190 (6)	0.0204 (6)	−0.0008 (5)	−0.0037 (5)	−0.0042 (5)
C5	0.0179 (6)	0.0199 (6)	0.0211 (6)	−0.0009 (5)	−0.0032 (5)	−0.0040 (5)
C7	0.0221 (7)	0.0264 (7)	0.0200 (6)	−0.0027 (5)	−0.0005 (5)	−0.0051 (5)
N2	0.0221 (5)	0.0240 (6)	0.0194 (5)	−0.0062 (4)	−0.0034 (4)	−0.0041 (4)
C3	0.0262 (7)	0.0182 (6)	0.0210 (6)	−0.0008 (5)	−0.0036 (5)	−0.0042 (5)
C9	0.0212 (6)	0.0205 (6)	0.0204 (6)	−0.0019 (5)	−0.0051 (5)	−0.0039 (5)
C8	0.0165 (6)	0.0259 (7)	0.0244 (7)	−0.0042 (5)	−0.0017 (5)	−0.0040 (5)
C1	0.0318 (7)	0.0265 (7)	0.0246 (7)	−0.0047 (6)	−0.0067 (6)	−0.0069 (6)
C16	0.0226 (6)	0.0245 (7)	0.0243 (7)	−0.0050 (5)	−0.0030 (5)	−0.0062 (5)
C4	0.0214 (6)	0.0209 (6)	0.0260 (7)	−0.0029 (5)	−0.0056 (5)	−0.0057 (5)
C13	0.0270 (7)	0.0334 (8)	0.0218 (7)	−0.0117 (6)	−0.0007 (6)	−0.0070 (6)
C11	0.0172 (6)	0.0354 (8)	0.0292 (7)	−0.0026 (5)	−0.0005 (5)	−0.0168 (6)
C14	0.0345 (8)	0.0324 (8)	0.0223 (7)	−0.0110 (6)	−0.0059 (6)	−0.0050 (6)
C15	0.0254 (7)	0.0218 (7)	0.0254 (7)	−0.0044 (5)	−0.0059 (5)	−0.0041 (5)
C12	0.0295 (7)	0.0458 (9)	0.0241 (7)	−0.0067 (7)	0.0020 (6)	−0.0120 (6)
O4	0.0386 (6)	0.0569 (8)	0.0344 (6)	−0.0012 (6)	−0.0048 (5)	−0.0258 (6)
N1	0.0249 (6)	0.0290 (6)	0.0251 (6)	−0.0057 (5)	−0.0037 (5)	−0.0098 (5)
C17	0.0244 (7)	0.0363 (8)	0.0328 (8)	0.0005 (6)	−0.0095 (6)	−0.0155 (6)

Geometric parameters (Å, º) top

F1—C8	1.3713 (15)	C16—N1	1.4594 (18)
O3—C3	1.2699 (17)	C16—C15	1.5243 (19)
O1—C1	1.2201 (19)	C16—H16A	0.9900
N3—C4	1.3428 (17)	C16—H16B	0.9900
N3—C5	1.4076 (17)	C4—H4	0.9500
N3—C11	1.4909 (17)	C13—C14	1.529 (2)
C2—C4	1.3822 (19)	C13—H13A	0.9900
C2—C3	1.4365 (19)	C13—H13B	0.9900
C2—C1	1.4908 (19)	C11—C12	1.520 (2)
O2—C1	1.3328 (18)	C11—H11A	0.9900
O2—H2	0.8400	C11—H11B	0.9900
C10—C9	1.3974 (18)	C14—N1	1.4619 (19)
C10—C5	1.4146 (19)	C14—H14A	0.9900
C10—H10	0.9500	C14—H14B	0.9900
C6—C5	1.4150 (18)	C15—H15A	0.9900
C6—C7	1.4175 (19)	C15—H15B	0.9900
C6—C3	1.4553 (19)	C12—H12A	0.9800
C7—C8	1.363 (2)	C12—H12B	0.9800
C7—H7	0.9500	C12—H12C	0.9800
N2—C9	1.4116 (17)	O4—C17	1.2298 (19)
N2—C13	1.4712 (17)	N1—C17	1.3435 (19)
N2—C15	1.4768 (17)	C17—H17	0.9500
C9—C8	1.4130 (19)

C4—N3—C5	119.98 (11)	N3—C4—C2	123.71 (12)
C4—N3—C11	118.71 (11)	N3—C4—H4	118.1
C5—N3—C11	121.30 (11)	C2—C4—H4	118.1
C4—C2—C3	120.16 (12)	N2—C13—C14	108.92 (11)
C4—C2—C1	118.61 (12)	N2—C13—H13A	109.9
C3—C2—C1	121.20 (12)	C14—C13—H13A	109.9
C1—O2—H2	109.5	N2—C13—H13B	109.9
C9—C10—C5	120.53 (12)	C14—C13—H13B	109.9
C9—C10—H10	119.7	H13A—C13—H13B	108.3
C5—C10—H10	119.7	N3—C11—C12	113.11 (12)
C5—C6—C7	119.28 (12)	N3—C11—H11A	109.0
C5—C6—C3	121.07 (12)	C12—C11—H11A	109.0
C7—C6—C3	119.66 (12)	N3—C11—H11B	109.0
N3—C5—C10	120.87 (12)	C12—C11—H11B	109.0
N3—C5—C6	119.15 (12)	H11A—C11—H11B	107.8
C10—C5—C6	119.97 (12)	N1—C14—C13	110.16 (12)
C8—C7—C6	119.10 (12)	N1—C14—H14A	109.6
C8—C7—H7	120.5	C13—C14—H14A	109.6
C6—C7—H7	120.5	N1—C14—H14B	109.6
C9—N2—C13	116.48 (11)	C13—C14—H14B	109.6
C9—N2—C15	113.88 (11)	H14A—C14—H14B	108.1
C13—N2—C15	111.25 (11)	N2—C15—C16	110.17 (11)
O3—C3—C2	122.95 (12)	N2—C15—H15A	109.6
O3—C3—C6	121.14 (12)	C16—C15—H15A	109.6
C2—C3—C6	115.91 (12)	N2—C15—H15B	109.6
C10—C9—N2	123.69 (12)	C16—C15—H15B	109.6
C10—C9—C8	117.67 (12)	H15A—C15—H15B	108.1
N2—C9—C8	118.60 (12)	C11—C12—H12A	109.5
C7—C8—F1	118.55 (12)	C11—C12—H12B	109.5
C7—C8—C9	123.45 (12)	H12A—C12—H12B	109.5
F1—C8—C9	117.96 (12)	C11—C12—H12C	109.5
O1—C1—O2	121.46 (13)	H12A—C12—H12C	109.5
O1—C1—C2	123.40 (13)	H12B—C12—H12C	109.5
O2—C1—C2	115.11 (12)	C17—N1—C16	122.70 (12)
N1—C16—C15	109.65 (11)	C17—N1—C14	122.50 (13)
N1—C16—H16A	109.7	C16—N1—C14	114.79 (11)
C15—C16—H16A	109.7	O4—C17—N1	125.40 (15)
N1—C16—H16B	109.7	O4—C17—H17	117.3
C15—C16—H16B	109.7	N1—C17—H17	117.3
H16A—C16—H16B	108.2

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O3	0.84	1.75	2.5315 (16)	155

Experimental details

Crystal data
Chemical formula	C₁₇H₁₈FN₃O₄
M_r	347.34
Crystal system, space group	Triclinic, P1
Temperature (K)	150
a, b, c (Å)	8.6689 (17), 9.6727 (19), 10.142 (2)
α, β, γ (°)	73.41 (3), 81.41 (3), 86.48 (3)
V (Å³)	805.8 (3)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.11
Crystal size (mm)	0.24 × 0.20 × 0.16

Data collection
Diffractometer	Nonius KappaCCD
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	6043, 3635, 2913
R_int	0.020
(sin θ/λ)_max (Å⁻¹)	0.647

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.043, 0.123, 1.05
No. of reflections	3635
No. of parameters	227
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.21, −0.25

Computer programs: COLLECT (Nonius, 1999), SCALEPACK (Otwinowski & Minor, 1997), SCALEPACK/DENZO (Otwinowski & Minor, 1997), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), X-SEED (Barbour, 2001).

Geometry (Å, °) of hydrogen bonds and π–π interactions top

Cg1 is the centroid of the N3/C2–C6 ring.

D-H···A	D-H(Å)	H···A(Å)	D···A(Å)	D-H···A(°)
O2—H2···O3	0.84	1.75	2.5315 (16)	154.5
C4-H4···O1ⁱ	0.95	2.36	3.1872	145
C10-H10···O4ⁱⁱ	0.95	2.58	3.4323	149
C11-H11A···O4ⁱⁱ	0.99	2.42	3.3413	155
C14-H14B···O3ⁱⁱⁱ	0.99	2.46	3.2465	136
C15-H15B···Cg1^iv	0.99	2.64	3.3749	131

Cg1···Cg1^v		3.423^a	3.8141^b	26^c

Notes: (a) Perpendicular distance of rings. (b) Distance between ring centroids. (c) Angle between the Cg1→Cg1^v vector and the normal to the plane of Cg1^v.

Symmetry codes: (i) 2-x,2-y,2-z; (ii)1-x,1-y,1-z; (iii) x,y,z-1; (iv)1-x,1-y,2-z; (v) 1-x,2-y,2-z

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1-Ethyl-6-fluoro-7-(4-formyl­piperazin-1-yl)-4-oxo-1,4-dihydro­quinoline-3-carboxylic acid

Supporting information

Key indicators

checkCIF/PLATON results

1-Ethyl-6-fluoro-7-(4-formylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid