organic compounds
7-Fluoro-6-nitroquinazolin-4(3H)-one
aSchool of Pharmaceutical Sciences, Nanjing University of Technology, No. 5 Xinmofan Road, Nanjing 210009, People's Republic of China, and bDepartment of Medicinal Chemistry, Jiangsu Provincial Institute of Materia Medica, Nanjing University of Technology, No. 26 Majia Street, Nanjing 210009, People's Republic of China
*Correspondence e-mail: fafazhang928@yahoo.com.cn
The quinazolinone unit of the title compound, C8H4FN3O3, is essentially planar, with a maximum deviation of 0.0538 (14) Å for the O atom. The nitro group is twisted by 12.0 (3)° from the mean plane of the quinazolinone ring system. The is stabilized by intermolecular N—H⋯O, C—H⋯N and C—H⋯O hydrogen bonds.
Related literature
The title compound is used as an intermediate for the production of several multi-targeted Raf kinase inhibitors, such as 4(3H)-quinazolinone and its derivatives, see: Bridges et al. (1996); Kim et al. (2008). For the antitumor activities of quinolines, see: Labuda et al. (2009). For synthetic aspects, see: Rewcastle et al. (1996). For bond-length data, see: Allen et al. (1987).
Experimental
Crystal data
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Refinement
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Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994); cell 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: PLATON (Spek, 2009).
Supporting information
10.1107/S1600536809046984/pv2231sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536809046984/pv2231Isup2.hkl
The title compound, was prepared by following a reported procedure (Rewcastle et al., 1996). 7-Fluoroquinazolin-4(3H)-one (47.4 g, 0.29 mmol) was added to a mixture of concentrated H2SO4 (100 ml) and fuming HNO3 (100 ml), and heated at 373 K for 1 h. The crude product, 7-fluoro-6-nitroquinazolin-4(3H)-one, was obtained by pouring the reacting mixture onto ice-water (1500 ml). The crystals of (I) suitable for X-ray diffraction studies were obtained by recrystallization from acetic acid.
H atoms were positioned geometrically at distances N—H = 0.86 Å and C—H = 0.93 Å and constrained to ride on their parent atoms, with Uiso(H) = 1.2 times Ueq(parent atoms).
Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994); cell
CAD-4 EXPRESS (Enraf–Nonius, 1994); 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: PLATON (Spek, 2009).C8H4FN3O3 | Z = 2 |
Mr = 209.14 | F(000) = 212 |
Triclinic, P1 | Dx = 1.729 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 5.6360 (11) Å | Cell parameters from 25 reflections |
b = 8.409 (2) Å | θ = 9–13° |
c = 8.674 (2) Å | µ = 0.15 mm−1 |
α = 79.38 (3)° | T = 293 K |
β = 89.23 (3)° | Block, colorless |
γ = 83.83 (3)° | 0.30 × 0.20 × 0.20 mm |
V = 401.70 (16) Å3 |
Enraf–Nonius CAD-4 diffractometer | 1131 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.018 |
Graphite monochromator | θmax = 25.3°, θmin = 2.4° |
ω/2θ scans | h = 0→6 |
Absorption correction: ψ scan (North et al., 1968) | k = −10→10 |
Tmin = 0.956, Tmax = 0.971 | l = −10→10 |
1623 measured reflections | 3 standard reflections every 200 reflections |
1461 independent reflections | intensity decay: 1% |
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)] = 0.050 | H-atom parameters constrained |
wR(F2) = 0.160 | w = 1/[σ2(Fo2) + (0.1P)2 + 0.12P] where P = (Fo2 + 2Fc2)/3 |
S = 1.00 | (Δ/σ)max < 0.001 |
1461 reflections | Δρmax = 0.23 e Å−3 |
137 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: 0.062 (16) |
C8H4FN3O3 | γ = 83.83 (3)° |
Mr = 209.14 | V = 401.70 (16) Å3 |
Triclinic, P1 | Z = 2 |
a = 5.6360 (11) Å | Mo Kα radiation |
b = 8.409 (2) Å | µ = 0.15 mm−1 |
c = 8.674 (2) Å | T = 293 K |
α = 79.38 (3)° | 0.30 × 0.20 × 0.20 mm |
β = 89.23 (3)° |
Enraf–Nonius CAD-4 diffractometer | 1131 reflections with I > 2σ(I) |
Absorption correction: ψ scan (North et al., 1968) | Rint = 0.018 |
Tmin = 0.956, Tmax = 0.971 | 3 standard reflections every 200 reflections |
1623 measured reflections | intensity decay: 1% |
1461 independent reflections |
R[F2 > 2σ(F2)] = 0.050 | 0 restraints |
wR(F2) = 0.160 | H-atom parameters constrained |
S = 1.00 | Δρmax = 0.23 e Å−3 |
1461 reflections | Δρmin = −0.25 e Å−3 |
137 parameters |
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 | ||
F | 0.1138 (3) | 0.4301 (2) | −0.33786 (16) | 0.0639 (5) | |
N1 | 0.1677 (3) | 0.1637 (2) | 0.3773 (2) | 0.0413 (5) | |
H1A | 0.1629 | 0.1209 | 0.4752 | 0.050* | |
O1 | −0.1399 (3) | 0.0293 (2) | 0.32253 (18) | 0.0527 (6) | |
C1 | 0.3360 (4) | 0.2651 (3) | 0.3291 (3) | 0.0419 (6) | |
H1B | 0.4402 | 0.2828 | 0.4049 | 0.050* | |
N2 | 0.3644 (3) | 0.3390 (2) | 0.1878 (2) | 0.0406 (5) | |
C2 | 0.0044 (4) | 0.1261 (3) | 0.2775 (2) | 0.0380 (6) | |
O2 | −0.2795 (5) | 0.3272 (3) | −0.3951 (2) | 0.0932 (9) | |
C3 | 0.0261 (4) | 0.2086 (2) | 0.1159 (2) | 0.0331 (5) | |
N3 | −0.2740 (4) | 0.2376 (3) | −0.2685 (2) | 0.0486 (6) | |
O3 | −0.4036 (3) | 0.1313 (2) | −0.2327 (2) | 0.0630 (6) | |
C4 | −0.1305 (4) | 0.1862 (3) | 0.0011 (3) | 0.0376 (6) | |
H4A | −0.2523 | 0.1200 | 0.0276 | 0.045* | |
C5 | −0.1046 (4) | 0.2618 (3) | −0.1509 (3) | 0.0380 (5) | |
C6 | 0.0818 (4) | 0.3590 (3) | −0.1903 (2) | 0.0396 (6) | |
C7 | 0.2349 (4) | 0.3832 (3) | −0.0789 (3) | 0.0387 (6) | |
H7A | 0.3567 | 0.4491 | −0.1068 | 0.046* | |
C8 | 0.2091 (4) | 0.3091 (2) | 0.0771 (2) | 0.0334 (5) |
U11 | U22 | U33 | U12 | U13 | U23 | |
F | 0.0696 (10) | 0.0883 (11) | 0.0293 (8) | −0.0238 (8) | −0.0026 (6) | 0.0104 (7) |
N1 | 0.0493 (11) | 0.0479 (11) | 0.0260 (9) | −0.0160 (9) | −0.0022 (8) | 0.0010 (8) |
O1 | 0.0562 (11) | 0.0618 (11) | 0.0393 (9) | −0.0333 (8) | −0.0015 (7) | 0.0086 (8) |
C1 | 0.0434 (13) | 0.0495 (13) | 0.0342 (12) | −0.0154 (10) | −0.0056 (9) | −0.0051 (10) |
N2 | 0.0413 (10) | 0.0474 (11) | 0.0338 (10) | −0.0172 (8) | −0.0030 (8) | −0.0019 (8) |
C2 | 0.0401 (12) | 0.0390 (12) | 0.0338 (12) | −0.0107 (9) | −0.0005 (9) | −0.0001 (9) |
O2 | 0.1106 (19) | 0.123 (2) | 0.0446 (12) | −0.0476 (15) | −0.0370 (12) | 0.0113 (12) |
C3 | 0.0356 (11) | 0.0321 (11) | 0.0306 (11) | −0.0060 (9) | −0.0001 (8) | −0.0019 (8) |
N3 | 0.0487 (12) | 0.0573 (13) | 0.0421 (12) | −0.0065 (10) | −0.0087 (9) | −0.0138 (10) |
O3 | 0.0533 (11) | 0.0733 (13) | 0.0676 (13) | −0.0208 (10) | −0.0126 (9) | −0.0172 (10) |
C4 | 0.0372 (12) | 0.0385 (12) | 0.0385 (12) | −0.0115 (9) | −0.0015 (9) | −0.0063 (9) |
C5 | 0.0404 (12) | 0.0403 (12) | 0.0333 (11) | −0.0028 (10) | −0.0060 (9) | −0.0069 (9) |
C6 | 0.0450 (13) | 0.0434 (12) | 0.0273 (11) | −0.0041 (10) | 0.0026 (9) | 0.0009 (9) |
C7 | 0.0374 (12) | 0.0412 (12) | 0.0360 (12) | −0.0111 (9) | 0.0028 (9) | 0.0003 (9) |
C8 | 0.0316 (11) | 0.0358 (11) | 0.0322 (11) | −0.0067 (8) | −0.0004 (8) | −0.0032 (8) |
F—C6 | 1.328 (2) | C3—C4 | 1.391 (3) |
N1—C1 | 1.354 (3) | C3—C8 | 1.401 (3) |
N1—C2 | 1.371 (3) | N3—O3 | 1.208 (3) |
N1—H1A | 0.8600 | N3—C5 | 1.462 (3) |
O1—C2 | 1.222 (3) | C4—C5 | 1.367 (3) |
C1—N2 | 1.284 (3) | C4—H4A | 0.9300 |
C1—H1B | 0.9300 | C5—C6 | 1.401 (3) |
N2—C8 | 1.381 (3) | C6—C7 | 1.361 (3) |
C2—C3 | 1.455 (3) | C7—C8 | 1.394 (3) |
O2—N3 | 1.211 (3) | C7—H7A | 0.9300 |
C1—N1—C2 | 123.10 (18) | C5—C4—C3 | 119.7 (2) |
C1—N1—H1A | 118.4 | C5—C4—H4A | 120.1 |
C2—N1—H1A | 118.4 | C3—C4—H4A | 120.1 |
N2—C1—N1 | 125.7 (2) | C4—C5—C6 | 119.8 (2) |
N2—C1—H1B | 117.2 | C4—C5—N3 | 118.4 (2) |
N1—C1—H1B | 117.2 | C6—C5—N3 | 121.8 (2) |
C1—N2—C8 | 115.98 (18) | F—C6—C7 | 118.2 (2) |
O1—C2—N1 | 121.96 (19) | F—C6—C5 | 120.7 (2) |
O1—C2—C3 | 124.5 (2) | C7—C6—C5 | 121.1 (2) |
N1—C2—C3 | 113.51 (19) | C6—C7—C8 | 120.0 (2) |
C4—C3—C8 | 120.5 (2) | C6—C7—H7A | 120.0 |
C4—C3—C2 | 120.43 (19) | C8—C7—H7A | 120.0 |
C8—C3—C2 | 119.07 (19) | N2—C8—C7 | 118.51 (19) |
O3—N3—O2 | 123.8 (2) | N2—C8—C3 | 122.58 (19) |
O3—N3—C5 | 118.1 (2) | C7—C8—C3 | 118.91 (19) |
O2—N3—C5 | 118.1 (2) | ||
C2—N1—C1—N2 | 0.6 (4) | O2—N3—C5—C6 | −14.0 (4) |
N1—C1—N2—C8 | −0.8 (4) | C4—C5—C6—F | 178.24 (19) |
C1—N1—C2—O1 | 177.0 (2) | N3—C5—C6—F | −1.5 (4) |
C1—N1—C2—C3 | −1.4 (3) | C4—C5—C6—C7 | −1.7 (4) |
O1—C2—C3—C4 | 3.2 (4) | N3—C5—C6—C7 | 178.6 (2) |
N1—C2—C3—C4 | −178.5 (2) | F—C6—C7—C8 | −179.23 (19) |
O1—C2—C3—C8 | −175.9 (2) | C5—C6—C7—C8 | 0.7 (4) |
N1—C2—C3—C8 | 2.5 (3) | C1—N2—C8—C7 | −178.6 (2) |
C8—C3—C4—C5 | 0.5 (3) | C1—N2—C8—C3 | 2.0 (3) |
C2—C3—C4—C5 | −178.60 (19) | C6—C7—C8—N2 | −178.6 (2) |
C3—C4—C5—C6 | 1.1 (3) | C6—C7—C8—C3 | 0.8 (3) |
C3—C4—C5—N3 | −179.19 (19) | C4—C3—C8—N2 | 178.01 (19) |
O3—N3—C5—C4 | −12.3 (3) | C2—C3—C8—N2 | −2.9 (3) |
O2—N3—C5—C4 | 166.3 (2) | C4—C3—C8—C7 | −1.4 (3) |
O3—N3—C5—C6 | 167.4 (2) | C2—C3—C8—C7 | 177.65 (19) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1A···O1i | 0.86 | 1.98 | 2.815 (2) | 165 |
C1—H1B···O2ii | 0.93 | 2.47 | 3.396 (3) | 179 |
C7—H7A···N2iii | 0.93 | 2.50 | 3.422 (3) | 171 |
Symmetry codes: (i) −x, −y, −z+1; (ii) x+1, y, z+1; (iii) −x+1, −y+1, −z. |
Experimental details
Crystal data | |
Chemical formula | C8H4FN3O3 |
Mr | 209.14 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 293 |
a, b, c (Å) | 5.6360 (11), 8.409 (2), 8.674 (2) |
α, β, γ (°) | 79.38 (3), 89.23 (3), 83.83 (3) |
V (Å3) | 401.70 (16) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.15 |
Crystal size (mm) | 0.30 × 0.20 × 0.20 |
Data collection | |
Diffractometer | Enraf–Nonius CAD-4 diffractometer |
Absorption correction | ψ scan (North et al., 1968) |
Tmin, Tmax | 0.956, 0.971 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 1623, 1461, 1131 |
Rint | 0.018 |
(sin θ/λ)max (Å−1) | 0.601 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.050, 0.160, 1.00 |
No. of reflections | 1461 |
No. of parameters | 137 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.23, −0.25 |
Computer programs: CAD-4 EXPRESS (Enraf–Nonius, 1994), XCAD4 (Harms & Wocadlo, 1995), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL(Sheldrick, 2008), PLATON (Spek, 2009).
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1A···O1i | 0.86 | 1.98 | 2.815 (2) | 165 |
C1—H1B···O2ii | 0.93 | 2.47 | 3.396 (3) | 179 |
C7—H7A···N2iii | 0.93 | 2.50 | 3.422 (3) | 171 |
Symmetry codes: (i) −x, −y, −z+1; (ii) x+1, y, z+1; (iii) −x+1, −y+1, −z. |
Acknowledgements
This research work was supported financially by the Research Funds of Jiangsu Provincial Institute of Materia Medica (No. SX200801).
References
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This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
4(3H)-Quinazolinone and its derivatives have been investigated extensively, owning to their important role in the synthesis of several multi-kinase inhibitors and to their potentially beneficial antitumor activities in many types of malignancies (Labuda et al., 2009).
As part of our studies on the synthesis of 4(3H)-quinazolinone and its derivatives, the title compound, (I), which is used as the key intermediate (Rewcastle et al., 1996), has been synthesized in our laboratory. We report herein the crystal structure of the title compound.
The molecule of the title compound is planar (Fig. 1). The quinazolinone moiety is essentially planar with maximum deviation for for any atoms being 0.0538 (14) for O1. The nitro group is twisted from the mean-plane of the quinazolinone ring by 12.0 (3)°. The bond lengths and angles in (I) are within normal ranges (Allen et al., 1987). The crtstal structure of (I) is stabilized by classical and non-classical intermolecular hydrogen bonds of the types N—H···O, C—H···N and C—H···O; details have been provided in Table 1 and presented as a packing diagram in Fig. 2.