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Acta Cryst. (2008). E64, o2240    [ doi:10.1107/S1600536808035058 ]

3-(2-Aminoethyl)-2-(4-fluoroanilino)quinazolin-4(3H)-one

X.-H. Yang and M.-H. Wu

Abstract top

In the title molecule, C16H15FN4O, the dihedral angle between the fluoro-substituted benzene ring and the pyrimidinone ring is 52.34 (7)°, while the dihedral angle between the fused benzene ring and the pyrimidinone ring is 3.30 (6)°. An intramolecular N-H...N hydrogen bond may, in part, influence the conformation of the molecule. In the crystal structure, intermolecular N-H...N hydrogen bonds and weak C-H...[pi](arene) interactions link pairs of molecules into centrosymmetric dimers.

Comment top

Quinazolinones and their derivatives are now known to have a wide range of useful biological properties, such as hypnotic, sedative, analgesic, anti-convulsant, anti-tussive, anti-bacterial, anti-diabetic, anti-inflammatory and anti-tumor (Armarego, 1963; Witt & Bergman, 2003). In connection with our ongoing heterocyclic synthesis and drug discovery project (Yang et al., 2008), we have focused our research on the synthesis of quinazolinones and pyrazolo pyrimidinones. Herein, the title compound was synthesized and its crystal structure was determined.

In the molecule (Fig. 1), the dihedral angle between the fluorophenyl and pyrimidinone ring is 52.34 (7)°, and the dihedral angle between the fused benzene ring and pyrimidinone ring is 3.30 (6)°. The torsion angles of N2–C7–N1–C4 and N3–C7–N1–C4 are -4.7 (2) and 176.42 (11)°, respectively.

An intramolecular N-H···N hydrogen bond may, in part, influence the conformation of the molecule. In the crystal structure, intermolecular N-H···N hydrogen bonds and weak C–H···π(arene) interactions link pairs of molecules into centrosymmetric dimers (see Table 1 and Fig. 2).

Related literature top

For the biological properties of quinazolinones and their derivatives, see: Armarego (1963); Witt & Bergman (2003). For our ongoing heterocyclic synthesis and drugdiscovery project, see: Yang et al. (2008). Cg is the centroid of atoms N2/C7/N3/C14/C13/C8.

Experimental top

To a solution of 2-ethoxycarbonyliminophosphorane (1.27 g, 3 mmol) in 10 ml anhydrous THF, 4-chlorophenylisocyanate (0.46 g, 3 mmol) was added dropwise at room temperature. The reaction mixture was left unstirred for 6 h at 273–278 K, whereafter the above resulting solution was added dropwise to a solution of ethylenediamine (0.18 g, 3 mmol) in 5 ml anhydrous THF. After that, the reaction mixture was stirred overnight, the reaction mixture was cooled and the reaction product was recrystallized from CH3OH—CH2Cl2 to give colorless crystals of the title compound in yield 85%, which were suitable for X-ray analysis.

Refinement top

H atoms bonded to C atoms were placed in calculated positions (C—H = 0.93–0.97 Å) and included in the riding model approximation. The positional parameters of H atoms bonded to N atoms were refined independently. For all H atoms Uiso (H) = 1.2Uiso (C,N).

Computing details top

Data collection: SMART (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. View of the title molecule with the atom-labeling scheme. Displacement ellipsoids are drawn at the 50% probability level.
[Figure 2] Fig. 2. Part of the crystal structure of the title compound showing hydrogen bonds as dashed lines.
3-(2-Aminoethyl)-2-(4-fluoroanilino)quinazolin-4(3H)-one top
Crystal data top
C16H15FN4OZ = 2
Mr = 298.32F(000) = 312
Triclinic, P1Dx = 1.407 Mg m−3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 8.2836 (8) ÅCell parameters from 2276 reflections
b = 9.3103 (10) Åθ = 2.2–28.9°
c = 9.4952 (10) ŵ = 0.10 mm−1
α = 89.36 (1)°T = 292 K
β = 80.537 (10)°Block, colourless
γ = 77.163 (10)°0.20 × 0.10 × 0.10 mm
V = 704.03 (13) Å3
Data collection top
Bruker SMART APEX CCD
diffractometer		2726 independent reflections
Radiation source: fine-focus sealed tube2318 reflections with I > 2σ(I)
graphiteRint = 0.012
ω scansθmax = 26.0°, θmin = 2.2°
Absorption correction: multi-scan
(SADABS; Bruker, 2001)		h = −9→10
Tmin = 0.970, Tmax = 0.990k = −11→11
4078 measured reflectionsl = −11→11
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.038H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.111 w = 1/[σ2(Fo2) + (0.0572P)2 + 0.1074P]
where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max = 0.001
2726 reflectionsΔρmax = 0.16 e Å−3
209 parametersΔρmin = −0.15 e Å−3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.033 (5)
Crystal data top
C16H15FN4Oγ = 77.163 (10)°
Mr = 298.32V = 704.03 (13) Å3
Triclinic, P1Z = 2
a = 8.2836 (8) ÅMo Kα radiation
b = 9.3103 (10) ŵ = 0.10 mm−1
c = 9.4952 (10) ÅT = 292 K
α = 89.36 (1)°0.20 × 0.10 × 0.10 mm
β = 80.537 (10)°
Data collection top
Bruker SMART APEX CCD
diffractometer		2726 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2001)		2318 reflections with I > 2σ(I)
Tmin = 0.970, Tmax = 0.990Rint = 0.012
4078 measured reflectionsθmax = 26.0°
Refinement top
R[F2 > 2σ(F2)] = 0.038H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.111Δρmax = 0.16 e Å−3
S = 1.05Δρmin = −0.15 e Å−3
2726 reflectionsAbsolute structure: ?
209 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
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
xyzUiso*/Ueq
C10.26560 (18)0.91647 (15)0.45066 (18)0.0596 (4)
C20.1522 (2)0.87525 (15)0.37986 (16)0.0589 (4)
H20.14510.90310.28630.071*
C30.04783 (17)0.79107 (14)0.45047 (14)0.0503 (3)
H3−0.03080.76240.40400.060*
C40.05872 (15)0.74874 (13)0.58961 (14)0.0449 (3)
C50.17665 (17)0.79171 (15)0.65820 (16)0.0536 (3)
H50.18600.76320.75120.064*
C60.28049 (18)0.87722 (16)0.58782 (18)0.0604 (4)
H60.35900.90740.63330.073*
C7−0.02621 (15)0.55612 (14)0.74400 (13)0.0424 (3)
C80.15458 (16)0.37171 (14)0.83809 (13)0.0444 (3)
C90.31903 (18)0.30166 (17)0.85105 (16)0.0573 (4)
H90.40750.34400.81210.069*
C100.3511 (2)0.17169 (18)0.92037 (17)0.0670 (4)
H100.46130.12600.92720.080*
C110.2208 (2)0.10669 (18)0.98092 (18)0.0690 (4)
H110.24380.01771.02710.083*
C120.0591 (2)0.17479 (17)0.97182 (16)0.0587 (4)
H12−0.02840.13261.01360.070*
C130.02374 (16)0.30663 (14)0.90063 (13)0.0459 (3)
C14−0.14830 (17)0.37725 (15)0.88772 (14)0.0479 (3)
C15−0.33989 (16)0.58408 (16)0.79762 (15)0.0523 (3)
H15A−0.34620.68930.80100.063*
H15B−0.41530.56130.87990.063*
C16−0.39955 (16)0.54589 (16)0.66308 (16)0.0555 (4)
H16A−0.36510.44030.64470.067*
H16B−0.52120.57310.67720.067*
F10.36536 (13)1.00298 (12)0.38271 (13)0.0901 (4)
N1−0.06114 (14)0.67357 (13)0.65917 (13)0.0496 (3)
H1−0.151 (2)0.6763 (17)0.6150 (16)0.060*
N20.12716 (13)0.49763 (12)0.75954 (11)0.0459 (3)
H4A−0.2947 (19)0.5633 (17)0.4621 (17)0.055*
H4B−0.411 (2)0.6934 (17)0.5178 (15)0.055*
N3−0.16619 (13)0.50507 (12)0.80814 (11)0.0448 (3)
N4−0.33145 (16)0.62199 (16)0.53930 (14)0.0590 (3)
O1−0.27139 (13)0.33072 (12)0.94041 (12)0.0654 (3)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0477 (8)0.0456 (7)0.0809 (10)−0.0143 (6)0.0073 (7)0.0107 (7)
C20.0648 (9)0.0473 (7)0.0579 (8)−0.0098 (7)0.0053 (7)0.0068 (6)
C30.0511 (8)0.0419 (7)0.0559 (8)−0.0093 (6)−0.0050 (6)0.0015 (6)
C40.0364 (6)0.0387 (6)0.0566 (7)−0.0069 (5)−0.0015 (5)0.0050 (5)
C50.0434 (7)0.0536 (8)0.0647 (8)−0.0136 (6)−0.0081 (6)0.0092 (6)
C60.0413 (7)0.0536 (8)0.0880 (11)−0.0148 (6)−0.0097 (7)0.0079 (7)
C70.0381 (7)0.0470 (7)0.0433 (6)−0.0146 (5)−0.0034 (5)0.0022 (5)
C80.0434 (7)0.0514 (7)0.0409 (6)−0.0159 (6)−0.0071 (5)0.0053 (5)
C90.0435 (8)0.0697 (9)0.0620 (8)−0.0185 (7)−0.0115 (6)0.0179 (7)
C100.0518 (9)0.0761 (10)0.0731 (10)−0.0097 (8)−0.0183 (7)0.0242 (8)
C110.0698 (10)0.0655 (10)0.0738 (10)−0.0170 (8)−0.0177 (8)0.0287 (8)
C120.0584 (9)0.0619 (9)0.0592 (8)−0.0235 (7)−0.0063 (7)0.0159 (7)
C130.0462 (7)0.0517 (7)0.0421 (6)−0.0177 (6)−0.0050 (5)0.0039 (5)
C140.0447 (7)0.0547 (7)0.0460 (7)−0.0201 (6)−0.0007 (5)0.0026 (6)
C150.0348 (7)0.0582 (8)0.0595 (8)−0.0086 (6)0.0028 (6)0.0021 (6)
C160.0334 (7)0.0580 (8)0.0755 (9)−0.0106 (6)−0.0095 (6)0.0043 (7)
F10.0763 (7)0.0820 (7)0.1149 (9)−0.0407 (6)0.0059 (6)0.0289 (6)
N10.0379 (6)0.0532 (7)0.0607 (7)−0.0154 (5)−0.0099 (5)0.0125 (5)
N20.0382 (6)0.0514 (6)0.0498 (6)−0.0157 (5)−0.0054 (4)0.0094 (5)
N30.0353 (6)0.0517 (6)0.0476 (6)−0.0142 (5)−0.0013 (4)0.0029 (5)
N40.0429 (7)0.0710 (8)0.0621 (8)−0.0101 (6)−0.0096 (6)0.0019 (6)
O10.0476 (6)0.0723 (7)0.0788 (7)−0.0275 (5)0.0011 (5)0.0166 (5)
Geometric parameters (Å, °) top
C1—C21.362 (2)C10—C111.392 (2)
C1—F11.3626 (16)C10—H100.9300
C1—C61.366 (2)C11—C121.365 (2)
C2—C31.3819 (19)C11—H110.9300
C2—H20.9300C12—C131.3914 (19)
C3—C41.3859 (19)C12—H120.9300
C3—H30.9300C13—C141.4551 (19)
C4—C51.388 (2)C14—O11.2254 (15)
C4—N11.4123 (16)C14—N31.3955 (17)
C5—C61.3870 (19)C15—N31.4821 (16)
C5—H50.9300C15—C161.516 (2)
C6—H60.9300C15—H15A0.9700
C7—N21.2980 (16)C15—H15B0.9700
C7—N11.3581 (17)C16—N41.464 (2)
C7—N31.3956 (15)C16—H16A0.9700
C8—N21.3785 (16)C16—H16B0.9700
C8—C91.3981 (19)N1—H10.908 (17)
C8—C131.4023 (18)N4—H4A0.889 (16)
C9—C101.366 (2)N4—H4B0.872 (16)
C9—H90.9300
C2—C1—F1118.49 (14)C10—C11—H11120.3
C2—C1—C6122.61 (13)C11—C12—C13120.67 (14)
F1—C1—C6118.88 (15)C11—C12—H12119.7
C1—C2—C3118.37 (14)C13—C12—H12119.7
C1—C2—H2120.8C12—C13—C8120.13 (13)
C3—C2—H2120.8C12—C13—C14120.69 (12)
C2—C3—C4120.93 (13)C8—C13—C14119.18 (12)
C2—C3—H3119.5O1—C14—N3120.70 (12)
C4—C3—H3119.5O1—C14—C13124.22 (13)
C3—C4—C5119.19 (12)N3—C14—C13115.08 (11)
C3—C4—N1117.79 (12)N3—C15—C16113.90 (11)
C5—C4—N1122.81 (12)N3—C15—H15A108.8
C6—C5—C4119.92 (14)C16—C15—H15A108.8
C6—C5—H5120.0N3—C15—H15B108.8
C4—C5—H5120.0C16—C15—H15B108.8
C1—C6—C5118.98 (14)H15A—C15—H15B107.7
C1—C6—H6120.5N4—C16—C15111.68 (12)
C5—C6—H6120.5N4—C16—H16A109.3
N2—C7—N1120.96 (11)C15—C16—H16A109.3
N2—C7—N3124.41 (11)N4—C16—H16B109.3
N1—C7—N3114.62 (11)C15—C16—H16B109.3
N2—C8—C9119.28 (12)H16A—C16—H16B107.9
N2—C8—C13122.38 (12)C7—N1—C4124.69 (11)
C9—C8—C13118.27 (12)C7—N1—H1114.5 (10)
C10—C9—C8120.65 (14)C4—N1—H1115.2 (10)
C10—C9—H9119.7C7—N2—C8117.77 (11)
C8—C9—H9119.7C14—N3—C7121.02 (11)
C9—C10—C11120.84 (14)C14—N3—C15116.82 (11)
C9—C10—H10119.6C7—N3—C15122.16 (11)
C11—C10—H10119.6C16—N4—H4A112.6 (10)
C12—C11—C10119.42 (14)C16—N4—H4B109.1 (10)
C12—C11—H11120.3H4A—N4—H4B106.8 (14)
F1—C1—C2—C3−178.16 (12)C8—C13—C14—O1−178.72 (13)
C6—C1—C2—C30.4 (2)C12—C13—C14—N3−177.09 (12)
C1—C2—C3—C4−0.4 (2)C8—C13—C14—N31.78 (18)
C2—C3—C4—C5−0.1 (2)N3—C15—C16—N4−78.30 (15)
C2—C3—C4—N1174.74 (12)N2—C7—N1—C4−4.7 (2)
C3—C4—C5—C60.7 (2)N3—C7—N1—C4176.42 (11)
N1—C4—C5—C6−173.93 (12)C3—C4—N1—C7138.77 (13)
C2—C1—C6—C50.2 (2)C5—C4—N1—C7−46.58 (19)
F1—C1—C6—C5178.68 (12)N1—C7—N2—C8−174.97 (11)
C4—C5—C6—C1−0.7 (2)N3—C7—N2—C83.84 (19)
N2—C8—C9—C10−175.78 (14)C9—C8—N2—C7176.85 (12)
C13—C8—C9—C101.3 (2)C13—C8—N2—C7−0.13 (19)
C8—C9—C10—C11−0.6 (3)O1—C14—N3—C7−177.93 (12)
C9—C10—C11—C12−0.6 (3)C13—C14—N3—C71.58 (17)
C10—C11—C12—C131.2 (3)O1—C14—N3—C153.07 (19)
C11—C12—C13—C8−0.5 (2)C13—C14—N3—C15−177.42 (11)
C11—C12—C13—C14178.40 (13)N2—C7—N3—C14−4.69 (19)
N2—C8—C13—C12176.23 (12)N1—C7—N3—C14174.18 (11)
C9—C8—C13—C12−0.8 (2)N2—C7—N3—C15174.25 (12)
N2—C8—C13—C14−2.65 (19)N1—C7—N3—C15−6.87 (17)
C9—C8—C13—C14−179.65 (12)C16—C15—N3—C14−96.27 (14)
C12—C13—C14—O12.4 (2)C16—C15—N3—C784.75 (15)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···N40.908 (17)1.925 (17)2.8049 (17)162.8 (14)
N4—H4A···N2i0.889 (16)2.323 (16)3.1321 (18)151.4 (13)
C3—H3···Cgi0.932.77 (1)3.4741 (15)132 (1)
Symmetry codes: (i) −x, −y+1, −z+1.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···N40.908 (17)1.925 (17)2.8049 (17)162.8 (14)
N4—H4A···N2i0.889 (16)2.323 (16)3.1321 (18)151.4 (13)
C3—H3···Cgi0.932.77 (1)3.4741 (15)132 (1)
Symmetry codes: (i) −x, −y+1, −z+1.
Acknowledgements top

We gratefully acknowledge financial support of this work by the the Natural Science Foundation of Hubei Province (grant No. 2006ABA334).

references
References top

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Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Spek, A. L. (2003). J. Appl. Cryst. 36, 7–13.

Witt, A. & Bergman, J. (2003). Curr. Org. Chem. 7, 659–677.

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