Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270109009391/fg3082sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270109009391/fg3082Isup2.hkl |
CCDC reference: 730116
The title compound could be easily prepared by nucleophilic vinylic substitution of equimolar amounts of (E)-methyl 2-methoxymethylene-3-oxobutanoate with 2-fluoroaniline in boiling ethanol (Leyva et al., 1999).
For the X-ray data, H atoms were constrained to ideal geometry using an appropriate riding model, with C—H = 0.95–0.98 Å and N—H = 0.88 Å. For methyl groups, the C—H distances and C—C—H or O—C—H angles (109.5°) were kept fixed, while the torsion agles were allowed to refine, with their starting positions based on the circular Fourier synthesis averaged using a local three-fold symmetry. Uiso(H) values were set at 1.3Ueq(Caromatic), 1.3Ueq(Namide) and 1.5Ueq(Cmethyl). Molecular calculations were carried out at the B3LYP/6–31+G** level of theory using GAUSSIAN98 (Frisch et al., 1998). Natural bond orbital (Foster & Weinhold, 1980) calculations were carried out using the NBO program (Glendening et al., 1993) included in the GAUSSIAN98 package.
Data collection: SMART (Bruker, 2003); cell refinement: SAINT (Bruker, 2003); data reduction: SAINT (Bruker, 2003) and SADABS (Sheldrick, 2003); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg, 2008); software used to prepare material for publication: PLATON (Spek, 2003).
C12H12FNO3 | Z = 2 |
Mr = 237.23 | F(000) = 248 |
Triclinic, P1 | Dx = 1.421 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 7.6772 (11) Å | Cell parameters from 2057 reflections |
b = 7.7591 (11) Å | θ = 2.7–32.6° |
c = 9.9774 (14) Å | µ = 0.11 mm−1 |
α = 100.718 (3)° | T = 153 K |
β = 107.473 (3)° | Prism, colourless |
γ = 91.827 (3)° | 0.11 × 0.09 × 0.07 mm |
V = 554.58 (14) Å3 |
Siemens SMART CCD area-detector diffractometer | 3743 independent reflections |
Radiation source: fine-focus sealed tube | 2388 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.030 |
Detector resolution: 120 µm pixels mm-1 | θmax = 32.0°, θmin = 2.7° |
ω scans | h = −11→11 |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | k = −11→11 |
Tmin = 0.497, Tmax = 0.992 | l = −14→14 |
7912 measured reflections |
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)] = 0.050 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.155 | H-atom parameters constrained |
S = 1.00 | w = 1/[σ2(Fo2) + (0.0842P)2 + 0.053P] where P = (Fo2 + 2Fc2)/3 |
3743 reflections | (Δ/σ)max < 0.001 |
162 parameters | Δρmax = 0.39 e Å−3 |
0 restraints | Δρmin = −0.26 e Å−3 |
C12H12FNO3 | γ = 91.827 (3)° |
Mr = 237.23 | V = 554.58 (14) Å3 |
Triclinic, P1 | Z = 2 |
a = 7.6772 (11) Å | Mo Kα radiation |
b = 7.7591 (11) Å | µ = 0.11 mm−1 |
c = 9.9774 (14) Å | T = 153 K |
α = 100.718 (3)° | 0.11 × 0.09 × 0.07 mm |
β = 107.473 (3)° |
Siemens SMART CCD area-detector diffractometer | 3743 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | 2388 reflections with I > 2σ(I) |
Tmin = 0.497, Tmax = 0.992 | Rint = 0.030 |
7912 measured reflections |
R[F2 > 2σ(F2)] = 0.050 | 0 restraints |
wR(F2) = 0.155 | H-atom parameters constrained |
S = 1.00 | Δρmax = 0.39 e Å−3 |
3743 reflections | Δρmin = −0.26 e Å−3 |
162 parameters |
Experimental. Data were collected at 153 K using a Siemens SMART CCD diffractometer equipped with LT-2 A cooling device. A full sphere of reciprocal space was scanned by 0.3° steps in ω with a crystal-to-detector distance of 3.97 cm, 20 s per frame. Preliminary orientation matrix was obtained from the first 100 frames using SMART (Bruker, 2003). The collected frames were integrated using the preliminary orientation matrix which was updated every 100 frames. Final cell parameters were obtained by refinement on the position of 2057 reflections with I>10σ(I) after integration of all the frames data using SAINT (Bruker, 2003). |
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. |
x | y | z | Uiso*/Ueq | ||
F1 | 0.14484 (12) | 0.62536 (12) | 0.87407 (9) | 0.0360 (2) | |
O1 | 0.14641 (14) | 0.04424 (15) | 0.29809 (11) | 0.0343 (3) | |
O2 | −0.15645 (15) | −0.02382 (16) | 0.21324 (13) | 0.0445 (3) | |
O3 | −0.19821 (14) | 0.32505 (14) | 0.57472 (11) | 0.0312 (3) | |
N1 | 0.15222 (15) | 0.40195 (14) | 0.63775 (11) | 0.0217 (2) | |
H1 | 0.0525 | 0.4216 | 0.6622 | 0.052 (6)* | |
C1 | 0.31803 (17) | 0.49527 (16) | 0.73067 (13) | 0.0215 (3) | |
C2 | 0.48761 (18) | 0.47833 (18) | 0.70890 (14) | 0.0253 (3) | |
H2 | 0.4970 | 0.4000 | 0.6265 | 0.035 (5)* | |
C3 | 0.64344 (19) | 0.5758 (2) | 0.80737 (15) | 0.0295 (3) | |
H3 | 0.7591 | 0.5633 | 0.7920 | 0.045 (5)* | |
C4 | 0.6320 (2) | 0.69109 (19) | 0.92788 (15) | 0.0314 (3) | |
H4 | 0.7393 | 0.7576 | 0.9945 | 0.046 (5)* | |
C5 | 0.4641 (2) | 0.70908 (19) | 0.95086 (15) | 0.0306 (3) | |
H5 | 0.4546 | 0.7878 | 1.0330 | 0.050 (6)* | |
C6 | 0.31091 (19) | 0.61116 (18) | 0.85280 (14) | 0.0255 (3) | |
C7 | 0.13327 (17) | 0.28693 (16) | 0.51647 (13) | 0.0205 (3) | |
H7 | 0.2390 | 0.2696 | 0.4867 | 0.020 (4)* | |
C8 | −0.02987 (17) | 0.19048 (16) | 0.43030 (13) | 0.0210 (3) | |
C9 | −0.19731 (18) | 0.21201 (18) | 0.46891 (14) | 0.0233 (3) | |
C10 | −0.37341 (19) | 0.0992 (2) | 0.38388 (16) | 0.0302 (3) | |
H10A | −0.4649 | 0.1218 | 0.4341 | 0.045* | |
H10B | −0.3506 | −0.0254 | 0.3738 | 0.045* | |
H10C | −0.4193 | 0.1279 | 0.2886 | 0.045* | |
C11 | −0.02518 (18) | 0.06144 (17) | 0.30380 (14) | 0.0234 (3) | |
C12 | 0.1646 (2) | −0.0834 (2) | 0.17952 (16) | 0.0375 (4) | |
H12A | 0.0902 | −0.1931 | 0.1689 | 0.056* | |
H12B | 0.2935 | −0.1065 | 0.1978 | 0.056* | |
H12C | 0.1223 | −0.0375 | 0.0912 | 0.056* |
U11 | U22 | U33 | U12 | U13 | U23 | |
F1 | 0.0289 (5) | 0.0457 (5) | 0.0317 (5) | 0.0047 (4) | 0.0149 (4) | −0.0055 (4) |
O1 | 0.0213 (5) | 0.0412 (6) | 0.0314 (5) | −0.0002 (4) | 0.0086 (4) | −0.0146 (4) |
O2 | 0.0244 (5) | 0.0508 (7) | 0.0405 (6) | −0.0030 (5) | 0.0038 (4) | −0.0228 (5) |
O3 | 0.0246 (5) | 0.0375 (6) | 0.0304 (5) | 0.0027 (4) | 0.0124 (4) | −0.0024 (4) |
N1 | 0.0188 (5) | 0.0226 (5) | 0.0209 (5) | 0.0009 (4) | 0.0058 (4) | −0.0017 (4) |
C1 | 0.0202 (6) | 0.0213 (6) | 0.0196 (6) | 0.0015 (5) | 0.0038 (4) | 0.0001 (4) |
C2 | 0.0218 (6) | 0.0261 (6) | 0.0239 (6) | 0.0016 (5) | 0.0065 (5) | −0.0040 (5) |
C3 | 0.0213 (7) | 0.0324 (7) | 0.0296 (7) | 0.0013 (5) | 0.0054 (5) | −0.0020 (6) |
C4 | 0.0282 (7) | 0.0315 (7) | 0.0251 (7) | −0.0022 (6) | 0.0005 (5) | −0.0036 (6) |
C5 | 0.0333 (8) | 0.0305 (7) | 0.0212 (6) | 0.0010 (6) | 0.0055 (5) | −0.0060 (5) |
C6 | 0.0242 (7) | 0.0287 (7) | 0.0232 (6) | 0.0045 (5) | 0.0098 (5) | −0.0002 (5) |
C7 | 0.0184 (6) | 0.0198 (6) | 0.0217 (6) | 0.0028 (4) | 0.0055 (4) | 0.0010 (4) |
C8 | 0.0179 (6) | 0.0203 (6) | 0.0226 (6) | 0.0019 (4) | 0.0049 (4) | 0.0011 (5) |
C9 | 0.0193 (6) | 0.0247 (6) | 0.0255 (6) | 0.0031 (5) | 0.0061 (5) | 0.0051 (5) |
C10 | 0.0197 (6) | 0.0333 (7) | 0.0354 (8) | −0.0012 (5) | 0.0068 (5) | 0.0049 (6) |
C11 | 0.0200 (6) | 0.0224 (6) | 0.0245 (6) | 0.0016 (5) | 0.0047 (5) | 0.0002 (5) |
C12 | 0.0293 (8) | 0.0458 (9) | 0.0301 (7) | 0.0030 (6) | 0.0110 (6) | −0.0125 (6) |
F1—C6 | 1.3584 (16) | C4—H4 | 0.9500 |
O1—C11 | 1.3453 (17) | C5—C6 | 1.3758 (19) |
O1—C12 | 1.4394 (16) | C5—H5 | 0.9500 |
O2—C11 | 1.2075 (16) | C7—C8 | 1.3864 (17) |
O3—C9 | 1.2427 (16) | C7—H7 | 0.9500 |
N1—C7 | 1.3290 (16) | C8—C9 | 1.4545 (18) |
N1—C1 | 1.4096 (16) | C8—C11 | 1.4685 (17) |
N1—H1 | 0.8800 | C9—C10 | 1.5077 (18) |
C1—C6 | 1.3899 (17) | C10—H10A | 0.9800 |
C1—C2 | 1.3891 (18) | C10—H10B | 0.9800 |
C2—C3 | 1.3886 (18) | C10—H10C | 0.9800 |
C2—H2 | 0.9500 | C12—H12A | 0.9800 |
C3—C4 | 1.3864 (19) | C12—H12B | 0.9800 |
C3—H3 | 0.9500 | C12—H12C | 0.9800 |
C4—C5 | 1.383 (2) | ||
C11—O1—C12 | 116.23 (11) | N1—C7—H7 | 117.7 |
C7—N1—C1 | 125.73 (12) | C8—C7—H7 | 117.7 |
C7—N1—H1 | 117.1 | C7—C8—C9 | 120.49 (11) |
C1—N1—H1 | 117.1 | C7—C8—C11 | 117.78 (12) |
C6—C1—C2 | 117.96 (11) | C9—C8—C11 | 121.67 (11) |
C6—C1—N1 | 117.56 (12) | O3—C9—C8 | 120.25 (12) |
C2—C1—N1 | 124.48 (11) | O3—C9—C10 | 117.99 (13) |
C1—C2—C3 | 120.09 (12) | C8—C9—C10 | 121.76 (12) |
C1—C2—H2 | 120.0 | C9—C10—H10A | 109.5 |
C3—C2—H2 | 120.0 | C9—C10—H10B | 109.5 |
C4—C3—C2 | 120.68 (13) | H10A—C10—H10B | 109.5 |
C4—C3—H3 | 119.7 | C9—C10—H10C | 109.5 |
C2—C3—H3 | 119.7 | H10A—C10—H10C | 109.5 |
C3—C4—C5 | 119.81 (13) | H10B—C10—H10C | 109.5 |
C3—C4—H4 | 120.1 | O2—C11—O1 | 121.70 (12) |
C5—C4—H4 | 120.1 | O2—C11—C8 | 125.89 (13) |
C6—C5—C4 | 118.91 (13) | O1—C11—C8 | 112.41 (11) |
C6—C5—H5 | 120.5 | O1—C12—H12A | 109.5 |
C4—C5—H5 | 120.5 | O1—C12—H12B | 109.5 |
F1—C6—C5 | 119.89 (12) | H12A—C12—H12B | 109.5 |
F1—C6—C1 | 117.56 (12) | O1—C12—H12C | 109.5 |
C5—C6—C1 | 122.55 (13) | H12A—C12—H12C | 109.5 |
N1—C7—C8 | 124.65 (12) | H12B—C12—H12C | 109.5 |
C7—N1—C1—C6 | 179.70 (13) | C1—N1—C7—C8 | 176.77 (12) |
C7—N1—C1—C2 | −0.7 (2) | N1—C7—C8—C9 | 0.6 (2) |
C6—C1—C2—C3 | −0.1 (2) | N1—C7—C8—C11 | −176.64 (13) |
N1—C1—C2—C3 | −179.69 (13) | C7—C8—C9—O3 | 4.5 (2) |
C1—C2—C3—C4 | −0.2 (2) | C11—C8—C9—O3 | −178.37 (13) |
C2—C3—C4—C5 | 0.3 (2) | C7—C8—C9—C10 | −175.19 (13) |
C3—C4—C5—C6 | 0.0 (2) | C11—C8—C9—C10 | 1.9 (2) |
C4—C5—C6—F1 | 179.29 (13) | C12—O1—C11—O2 | −1.0 (2) |
C4—C5—C6—C1 | −0.4 (2) | C12—O1—C11—C8 | 178.31 (13) |
C2—C1—C6—F1 | −179.25 (12) | C7—C8—C11—O2 | −174.66 (15) |
N1—C1—C6—F1 | 0.33 (19) | C9—C8—C11—O2 | 8.1 (2) |
C2—C1—C6—C5 | 0.4 (2) | C7—C8—C11—O1 | 6.04 (18) |
N1—C1—C6—C5 | −179.97 (14) | C9—C8—C11—O1 | −171.17 (12) |
Experimental details
Crystal data | |
Chemical formula | C12H12FNO3 |
Mr | 237.23 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 153 |
a, b, c (Å) | 7.6772 (11), 7.7591 (11), 9.9774 (14) |
α, β, γ (°) | 100.718 (3), 107.473 (3), 91.827 (3) |
V (Å3) | 554.58 (14) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.11 |
Crystal size (mm) | 0.11 × 0.09 × 0.07 |
Data collection | |
Diffractometer | Siemens SMART CCD area-detector diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 2003) |
Tmin, Tmax | 0.497, 0.992 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 7912, 3743, 2388 |
Rint | 0.030 |
(sin θ/λ)max (Å−1) | 0.745 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.050, 0.155, 1.00 |
No. of reflections | 3743 |
No. of parameters | 162 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.39, −0.26 |
Computer programs: SMART (Bruker, 2003), SAINT (Bruker, 2003) and SADABS (Sheldrick, 2003), SHELXTL (Sheldrick, 2008), DIAMOND (Brandenburg, 2008), PLATON (Spek, 2003).
D—H···A | D—H | H···A | D···A | D—H···A | |
N1—H1···O3 | 0.88 | 1.92 | 2.5945 (15) | 132 | a |
1.029 | 1.806 | 2.613 | 132.48 | b | |
C4—H4···O2i | 0.95 | 2.40 | 3.2076 (17) | 142 | |
N1—H1···F1 | 0.88 | 2.29 | 2.6710 (13) | 106 | a |
1.029 | 2.316 | 2.690 | 99.83 | b | |
C7—H7···O1 | 0.95 | 2.24 | 2.6308 (15) | 104 | a |
1.083 | 2.219 | 2.653 | 101.36 | b |
Symmetry code: (i) x+1, y+1, z+1. |
Bond distance | WBO | |
F1-C6 | 1.3584 (16) | 0.89 |
C1-N1 | 1.4096 (16) | 1.06 |
N1-C7 | 1.3290 (16) | 1.30 |
C7-C8 | 1.3864 (17) | 1.47 |
C8-C9 | 1.4545 (18) | 1.11 |
C9-O3 | 1.2427 (16) | 1.64 |
C8-C11 | 1.4685 (17) | 1.09 |
C11-O1 | 1.3453 (17) | 0.99 |
C11-O2 | 1.2075 (16) | 1.68 |
C9-C10 | 1.5077 (18) | 1.03 |
Fluoroquinolones belong to an important group of drugs with antibacterial, immunomodulating or anticancerogenic effects. However, despite of their usefulness and their wide and numerous applications in medicinal practice, several objections concerning their toxicity have also been raised (see e.g. www.fluoroquinolones.org). The title compound, (I), was synthesized within the framework of our ongoing study (see e.g. Kettmann et al., 2004; Gróf, Milata, Kožíšek & Tokarčík, 2006; Gróf, Milata & Kožíšek, 2006; Gróf et al., 2008; Langer et al., 2007; Smrčok et al., 2007) of the structures and properties of precursors of fluoroquinolones, because knowledge of these compounds could prove essential in reaction pathway considerations and planning. The structure of (I) is reported here to determine its solid-state conformation and molecular geometry, particularly with reference to the relative positions of the ortho-substituent on the phenyl ring in relation to the enamino grouping and the substituents on the β-positions of the aminoethylene substituent.
Possible conformers (I) and (II) are shown in the scheme. Both conformers would be expected to have an intramolecular hydrogen bond between the imino H atom and the carbonyl of the acetyl group. The X-ray structure analysis establishes the preferred solid-state conformation as (I), which is shown in Fig. 1. The molecule is essentially planar and the most outlying atoms, C10 and C12, are displaced from the best-plane fit through all non H-atoms by -0.163 (2) (C10) and -0.118 (2) Å (C12). In the crystal structure, molecules are arranged in layers oriented parallel to the (011) plane. This arrangement is proposed to be fixed mainly by long-range electrostatic interactions, as the calculated dipole moment of the molecule is as large as 5.2 D. An intermolecular C—H···O hydrogen bond links the molecules within the layers and gives rise to chains with the base vector [1,1,1] (Fig. 2 and Table 1).
The shape of the molecule is stabilized by an N1—H1···O3 hydrogen bond and two attractive intramolecular contacts (Table 1). Since the `organic' F atoms form at best only very weak non-bonded contacts (Howard et al., 1996; Dunitz & Taylor, 1997), the contribution of the F1···H1 interaction to the stabilization energy is smaller than that of the O3···H1 interaction. Natural bond orbital (NBO; Foster & Weinhold, 1980) analysis (Table 2 [Shows WBO not NBO - please clarify]) of the molecular electronic structure reveals a general delocalization pattern, which can be depicted by the resonance structures shown in Fig. 3. The N lone pair is delocalized primarily into the π-antibonding orbital of the C7—C8 bond and also, due to the electron-withdrawing effect of atoms O2 and O3, to a smaller extent into the antibonding orbitals of the C9—O3 and C11—O2 bonds. The most obvious geometric consequences of such an electron redistribution are shortening of the formally single N1—C7 bond, lengthening of the formally double C7═C8 bond and structural rigidity of the N1—C7═C8—C9═O3 moiety. This last is further enhanced by the formation of an intramolecular N1—H1···O3 (Table 1) hydrogen bond. From the three lone electron pairs on the F atom (two sp2 and one p), the latter contributes to π* antibonding orbital of the benzene ring, while the two sp2 orbitals stay on the atom and are partially responsible for shortening of Car—F bond.
Geometric analysis also reveals a few deviations from ideal geometry for the contact of the benzene ring and the conjugated system. First, the value of the C6—C1—N1 bond angle of 117.56 (12)° is a compromise between electrostatic attraction between atoms F1 (NBO charge -0.342) and H1 (0.485) and repulsion of atoms H2 and H7, separated by only 2.08 Å. A simulation calculation for a model system with the F atom replaced by H clearly showed that this H—H repulsion plays a more important role than F—H attraction. The next conspicuous geometric feature of the molecule is the deviation of the C1—N1—C7 [125.73 (12)°] and N1—C7—C8 [124.65 (12)°] bond angles from the ideal value of 120°. A qualitative interpretation of this effect lies in the decreased p content of a formally sp2 hybrid, forming the σ part of a double bond (for details, see e.g. Bent, 1961). The main idea is that the hybrid orbital of C, which is involved in the double-bond, contains more than 33% s character (the ideal sp2 value). An increase in the s content of one hybrid means in turn an increase in the p character of another two hybrids, thus decreasing the angle between them from the ideal value of 120°. Indeed, the hybridization pattern of the natural orbitals shows increasing p content in both C—H and N—H bonds, and decreasing content in the C—N and C—C bonds. Consequently, bond angles involving H atoms should be less than the ideal value of 120° and the angles in the conjugated system should of course be larger.
Another interesting question is the existence of the hypothetical conformer, (II), related to (I) by rotation of the phenyl ring about the exocyclic C1—N1 bond. Our molecular calculations show that, although it would be stabilized by the formation of an intramolecular attractive contact formed by the moderately acidic atom H7 with atom F1 (H···F = 2.142 Å), its total energy in vacuo is 2.5 kJ mol-1 (1 kcal mol-1 = 4.184 kJ mol-1) higher than that of (I), the interconversion barrier height being 13.4 kJ mol-1. Moreover, due to its smaller dipole moment (4.10 D), the existence of (II) is even further disfavoured in such a polar environment as that used in the present synthesis. Calculation of the solvent effect by means of the PCM continuum model (Miertuš et al., 1981; Foresman et al., 1996) revealed that ethanol further stabilizes conformation (I), conformation (II) being less stable by 4.6 kJ mol-1. Additionally, in this environment the barrier for the interconversion of (II) to (I) is reduced to 9.2 kJ mol-1, thus making crystallization of (II) even less probable.