7-Fluoro-6-nitro­quinazolin-4(3H)-one

Wu, Y.; Ji, A.; Zhang, A.; Shen, Y.

doi:10.1107/S1600536809046984

organic compounds

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ISSN: 2056-9890

Volume 65| Part 12| December 2009| Page o3075

doi:10.1107/S1600536809046984

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7-Fluoro-6-nitroquinazolin-4(3H)-one

Yundeng Wu,^a,^b Ancheng Ji,^b Aihua Zhang ^b ^* and Yipeng Shen ^b

^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

(Received 30 October 2009; accepted 6 November 2009; online 14 November 2009)

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 crystal structure 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

C₈H₄FN₃O₃
M_r = 209.14
Triclinic, $[P \overline 1]$
a = 5.6360 (11) Å
b = 8.409 (2) Å
c = 8.674 (2) Å
α = 79.38 (3)°
β = 89.23 (3)°
γ = 83.83 (3)°
V = 401.70 (16) Å³
Z = 2
Mo Kα radiation
μ = 0.15 mm⁻¹
T = 293 K
0.30 × 0.20 × 0.20 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: ψ scan (North et al., 1968 ) T_min = 0.956, T_max = 0.971
1623 measured reflections
1461 independent reflections
1131 reflections with I > 2σ(I)
R_int = 0.018
3 standard reflections every 200 reflections intensity decay: 1%

Refinement

R[F² > 2σ(F²)] = 0.050
wR(F²) = 0.160
S = 1.00
1461 reflections
137 parameters
H-atom parameters constrained
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

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.

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: PLATON (Spek, 2009 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809046984/pv2231sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809046984/pv2231Isup2.hkl

checkCIF report

Comment top

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.

Related literature top

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 top

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.

Computing details top

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994); cell refinement: 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).

Figures top

	Fig. 1. The molecular structure of the titlecompound with the atom numbering scheme. Displacement ellipsoids are drawn at 30% probability levels.
	Fig. 2. A packing diagram of the title compound. Hydron bonds are shown as dashed lines.

7-Fluoro-6-nitroquinazolin-4(3H)-one top

Crystal data top

C₈H₄FN₃O₃	Z = 2
M_r = 209.14	F(000) = 212
Triclinic, P1	D_x = 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

Data collection top

Enraf–Nonius CAD-4 diffractometer	1131 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.018
Graphite monochromator	θ_max = 25.3°, θ_min = 2.4°
ω/2θ scans	h = 0→6
Absorption correction: ψ scan (North et al., 1968)	k = −10→10
T_min = 0.956, T_max = 0.971	l = −10→10
1623 measured reflections	3 standard reflections every 200 reflections
1461 independent reflections	intensity decay: 1%

Refinement top

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(F_o²) + (0.1P)² + 0.12P] where P = (F_o² + 2F_c²)/3
S = 1.00	(Δ/σ)_max < 0.001
1461 reflections	Δρ_max = 0.23 e Å⁻³
137 parameters	Δρ_min = −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)

Crystal data top

C₈H₄FN₃O₃	γ = 83.83 (3)°
M_r = 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)°

Data collection top

Enraf–Nonius CAD-4 diffractometer	1131 reflections with I > 2σ(I)
Absorption correction: ψ scan (North et al., 1968)	R_int = 0.018
T_min = 0.956, T_max = 0.971	3 standard reflections every 200 reflections
1623 measured reflections	intensity decay: 1%
1461 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.050	0 restraints
wR(F²) = 0.160	H-atom parameters constrained
S = 1.00	Δρ_max = 0.23 e Å⁻³
1461 reflections	Δρ_min = −0.25 e Å⁻³
137 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
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)

Atomic displacement parameters (Å²) top

	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)

Geometric parameters (Å, º) top

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)

Hydrogen-bond geometry (Å, º) top

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
M_r	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)
T_min, T_max	0.956, 0.971
No. of measured, independent and observed [I > 2σ(I)] reflections	1623, 1461, 1131
R_int	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
Δρ_max, Δρ_min (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).

Hydrogen-bond geometry (Å, º) top

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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