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Acta Cryst. (2007). E63, o3109
https://doi.org/10.1107/S1600536807026670
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6-Amino-2-(fluoro­meth­yl)-3-(2-methyl­phen­yl)quinazolin-4(3H)-one

S.-C. Chen, F.-H. Yin, Q. Chen, Q. Liu and M.-Y. He
In an effort to discover a novel and potent muscle relaxant, the title compound, C16H14FN3O, has been synthesized. In the mol­ecule, the pendant benzene ring is nearly perpendicular to the quinazoline system [dihedral angle = 87.60 (12)°]. Inter­molecular N—H...F, N—H...O and C—H...O hydrogen bonding helps to stabilize the crystal structure. The fluoro­methyl group shows rotational disorder, equally over two positions.
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Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807026670/xu2266sup1.cif
Contains datablocks I, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S1600536807026670/xu2266Isup2.hkl
Contains datablock I

CCDC reference: 654878

checkCIF report

Key indicators

  • Single-crystal X-ray study
  • T = 291 K
  • Mean [sigma](C-C) = 0.004 Å
  • Disorder in main residue
  • R factor = 0.063
  • wR factor = 0.154
  • Data-to-parameter ratio = 13.5

checkCIF/PLATON results

No syntax errors found




Alert level C
PLAT301_ALERT_3_C Main Residue  Disorder .........................       5.00 Perc.


   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   1 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   0 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
   1 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check
Comment top

Quninazolin-4(3H)-one is an alkaloid (Chou et al., 1948). Due to their biological activity, substituted quinazolin-4(3H)-ones represent one of the most interesting groups of heterocycles. In particular, quinazolin-4(3H)-one alkaloids such as asperlicin C, possessing cholecystokinin antagonist properties, and benzomalvins, which are neuro-kinin receptor antagonists, have attracted significant attention (Witt & Bergman, 2003; Michael, 2005). A number of derivatives of 6-amino-2-(fluoromethyl)-3-(2-methylphenyl)-3H-quinazolin-4-one have aroused considerable interest owing to their potent muscle relaxing activity and low toxicity (Tani et al., 1979).

The title compound (Figure 1) consists of a quinazoline ring with an amino group at C4, a disordered fluoromethyl substitutent at C8 and a 2-methylphenyl group at N1. The quinazoline fragment is nearly planar, with a maximum deviation from the least-squares plane of 0.034 (2) Å. The phenyl ring attached to N1 atom is orthogonal to the quinzaoline plane with a C1—N1—C10—C15 torsion angle of 85.0 (3)°. The bond lengths and bond angles are within the reported values (Allen et al., 1987). The distance of C1—O1 bond (1.203 (3) Å) is significantly shorter than the values for some analogous structures (Etter, 1983; Böcskei et al., 1995).

The fluoromethyl group is disordered over two positions, corresponding to rotation of approximately 120° about the single C8—C9 bond, with a major-minor ratio of about 50:50. Three intermolecular hydrogen bonding (N—H···F, N—H···O and C—H···O) (Table 1), as observed in the packing diagram (Fig. 2), are effective in stabilizing the crystal structure.

Related literature top

For general background, see: Chou et al. (1948); Witt & Bergman (2003); Michael (2005); Tani et al. (1979). For related structures, see: Allen et al. (1987); Etter (1983); Böcskei et al. (1995).

Experimental top

SnCl2.2H2O (13.56 g, 60 mmol) was added to a solution of 2-(fluoromethyl)-3-(2-methylphenyl)-6-nitro-3H-quinazolin-4-one (3.13 g, 10 mmol) in methanol (150 ml) below 273.15 K. After stirring at room temperature for 12 h, the reaction mixture was poured into ice water (300 ml) and neutralized with NaHCO3 solution. The mixture was extracted with chloroform (600 ml), dried over MgSO4, and then concentrated to dryness in vacuo. The crude product was purified by column chromatography on silica gel, eluent is petroleum ether/ethyl acetate (4:1) to give the title compound (yield 1.21 g, 42.6%). The crystals of (I) suitable for X-ray structure determination were obtained from heptane-ethyl acetate mixed solvent at room temperature. Analysis calcd. for C16H14FN3O: C 67.83, H 4.98, N 14.83%; Found: C 67.81, H 4.91, N 14.85%.

Refinement top

The fluoromethyl group is disordered over two sites with equal occupancy factors. Amino H atoms were located in a difference Fourier map and other H atoms were placed in calculated positions with C—H = 0.93–0.96 Å, and refined in riding model with Uiso(H)=1.2Ueq(C,N), or 1.5Ueq(C) for methyl.

Structure description top

Quninazolin-4(3H)-one is an alkaloid (Chou et al., 1948). Due to their biological activity, substituted quinazolin-4(3H)-ones represent one of the most interesting groups of heterocycles. In particular, quinazolin-4(3H)-one alkaloids such as asperlicin C, possessing cholecystokinin antagonist properties, and benzomalvins, which are neuro-kinin receptor antagonists, have attracted significant attention (Witt & Bergman, 2003; Michael, 2005). A number of derivatives of 6-amino-2-(fluoromethyl)-3-(2-methylphenyl)-3H-quinazolin-4-one have aroused considerable interest owing to their potent muscle relaxing activity and low toxicity (Tani et al., 1979).

The title compound (Figure 1) consists of a quinazoline ring with an amino group at C4, a disordered fluoromethyl substitutent at C8 and a 2-methylphenyl group at N1. The quinazoline fragment is nearly planar, with a maximum deviation from the least-squares plane of 0.034 (2) Å. The phenyl ring attached to N1 atom is orthogonal to the quinzaoline plane with a C1—N1—C10—C15 torsion angle of 85.0 (3)°. The bond lengths and bond angles are within the reported values (Allen et al., 1987). The distance of C1—O1 bond (1.203 (3) Å) is significantly shorter than the values for some analogous structures (Etter, 1983; Böcskei et al., 1995).

The fluoromethyl group is disordered over two positions, corresponding to rotation of approximately 120° about the single C8—C9 bond, with a major-minor ratio of about 50:50. Three intermolecular hydrogen bonding (N—H···F, N—H···O and C—H···O) (Table 1), as observed in the packing diagram (Fig. 2), are effective in stabilizing the crystal structure.

For general background, see: Chou et al. (1948); Witt & Bergman (2003); Michael (2005); Tani et al. (1979). For related structures, see: Allen et al. (1987); Etter (1983); Böcskei et al. (1995).

Computing details top

Data collection: SMART (Bruker, 2000); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Bruker, 2000); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Figures top
[Figure 1] Fig. 1. The molecular structure of (I) (thermal ellipsoids are shown at 30% probability levels).
[Figure 2] Fig. 2. A packing diagram for (I) (Dashed lines indicate hydrogen bonds).
6-Amino-2-(fluoromethyl)-3-(2-methylphenyl)quinazolin-4(3H)-one top
Crystal data top
C16H14FN3OF(000) = 592
Mr = 283.30Dx = 1.372 Mg m−3
Monoclinic, P21/cMelting point: 470 K
Hall symbol: -P 2ybcMo Kα radiation, λ = 0.71073 Å
a = 6.3100 (13) ÅCell parameters from 732 reflections
b = 12.310 (3) Åθ = 2.1–25.5°
c = 17.658 (4) ŵ = 0.10 mm−1
β = 90.24 (3)°T = 291 K
V = 1371.6 (5) Å3Block, yellow
Z = 40.30 × 0.26 × 0.24 mm
Data collection top
Bruker SMART APEX CCD
diffractometer		2172 reflections with I > 2σ(I)
Radiation source: sealed tubeRint = 0.019
Graphite monochromatorθmax = 26.0°, θmin = 2.0°
φ and ω scansh = −7→7
5223 measured reflectionsk = −15→15
2691 independent reflectionsl = −21→21
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.063Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.154H-atom parameters constrained
S = 1.06 w = 1/[σ2(Fo2) + (0.0562P)2 + 1.1526P]
where P = (Fo2 + 2Fc2)/3
2691 reflections(Δ/σ)max < 0.001
200 parametersΔρmax = 0.39 e Å−3
0 restraintsΔρmin = −0.36 e Å−3
Crystal data top
C16H14FN3OV = 1371.6 (5) Å3
Mr = 283.30Z = 4
Monoclinic, P21/cMo Kα radiation
a = 6.3100 (13) ŵ = 0.10 mm−1
b = 12.310 (3) ÅT = 291 K
c = 17.658 (4) Å0.30 × 0.26 × 0.24 mm
β = 90.24 (3)°
Data collection top
Bruker SMART APEX CCD
diffractometer		2172 reflections with I > 2σ(I)
5223 measured reflectionsRint = 0.019
2691 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0630 restraints
wR(F2) = 0.154H-atom parameters constrained
S = 1.06Δρmax = 0.39 e Å−3
2691 reflectionsΔρmin = −0.36 e Å−3
200 parameters
Special details top

Experimental. IR (KBr): 3468, 3369, 3065, 3040, 2956, 2925, 1672, 1628, 1608, 1489, 1357, 1274, 1107, 1030, 838, 761 cm-1; 1HNMR (d-Acetone, 300 MHz): σ 2.13 (s, 3H, CH3), 4.08 (s, 2H, NH2), 4.85(s, 1H, CH2F), 5.01 (s, 1H, CH2F) 7.15–7.67 (m, 7H, ArH).

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*/UeqOcc. (<1)
C10.3272 (4)0.37992 (19)0.06660 (14)0.0351 (5)
C20.2262 (3)0.29811 (18)0.01924 (13)0.0311 (5)
C30.0418 (4)0.3265 (2)−0.02108 (14)0.0378 (6)
H3−0.00840.3975−0.01970.045*
C4−0.0646 (4)0.2485 (2)−0.06276 (14)0.0395 (6)
C50.0130 (4)0.1430 (2)−0.06377 (14)0.0435 (6)
H5−0.05870.0902−0.09140.052*
C60.1975 (4)0.1146 (2)−0.02386 (14)0.0403 (6)
H60.24970.0440−0.02590.048*
C70.3005 (4)0.19287 (19)0.01852 (13)0.0333 (5)
C80.5704 (4)0.23229 (19)0.10110 (13)0.0334 (5)
C90.7671 (5)0.2024 (2)0.14313 (18)0.0559 (8)
H9A0.73790.19940.19640.067*0.50
H9C0.81600.13270.12620.067*0.50
H9B0.87440.25600.13380.067*
F10.8229 (5)0.1004 (3)0.1308 (2)0.0569 (9)0.50
F20.7462 (5)0.1867 (3)0.21687 (18)0.0554 (8)0.50
C100.5861 (3)0.40942 (19)0.16752 (14)0.0346 (6)
C110.7616 (4)0.4745 (2)0.15056 (15)0.0425 (6)
H110.82140.47350.10250.051*
C120.8429 (4)0.5396 (2)0.20645 (19)0.0557 (8)
H120.95750.58470.19620.067*
C130.7555 (5)0.5383 (2)0.27761 (17)0.0523 (8)
H130.81400.58100.31580.063*
C140.5837 (4)0.4750 (2)0.29274 (15)0.0425 (6)
H140.52520.47670.34100.051*
C150.4929 (4)0.4076 (2)0.23813 (14)0.0364 (5)
C160.3045 (5)0.3415 (3)0.25512 (18)0.0569 (8)
H16A0.18140.37470.23290.085*
H16B0.28670.33670.30900.085*
H16C0.32250.26990.23460.085*
N10.5001 (3)0.33912 (16)0.10830 (11)0.0328 (5)
N20.4853 (3)0.16129 (16)0.05817 (12)0.0379 (5)
N3−0.2479 (4)0.2761 (2)−0.10214 (15)0.0563 (7)
H3C−0.22560.2587−0.15100.068*
H3A−0.29340.3419−0.10110.068*
O10.2752 (3)0.47363 (14)0.07204 (12)0.0544 (6)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0318 (12)0.0284 (12)0.0451 (14)0.0018 (9)−0.0125 (10)−0.0001 (10)
C20.0304 (11)0.0321 (12)0.0309 (11)0.0006 (9)−0.0084 (9)0.0007 (9)
C30.0352 (12)0.0393 (13)0.0389 (13)0.0000 (10)−0.0164 (10)0.0014 (10)
C40.0374 (13)0.0440 (14)0.0369 (13)−0.0099 (11)−0.0137 (10)0.0058 (11)
C50.0550 (16)0.0387 (14)0.0365 (13)−0.0176 (12)−0.0145 (11)−0.0029 (11)
C60.0457 (14)0.0305 (12)0.0447 (14)−0.0049 (11)−0.0105 (11)−0.0040 (10)
C70.0303 (11)0.0342 (12)0.0352 (12)−0.0017 (9)−0.0002 (9)0.0016 (10)
C80.0276 (11)0.0389 (13)0.0338 (12)0.0036 (9)−0.0015 (9)−0.0023 (10)
C90.0507 (17)0.0490 (16)0.068 (2)0.0209 (13)−0.0260 (15)−0.0128 (14)
F10.0510 (18)0.0493 (19)0.070 (2)−0.0051 (15)−0.0137 (16)−0.0006 (16)
F20.0490 (18)0.069 (2)0.0482 (19)−0.0034 (16)−0.0059 (15)−0.0051 (16)
C100.0257 (11)0.0329 (12)0.0450 (14)0.0122 (9)−0.0143 (10)−0.0088 (10)
C110.0417 (14)0.0442 (14)0.0416 (14)−0.0082 (11)−0.0028 (11)−0.0052 (11)
C120.0375 (14)0.0478 (16)0.082 (2)−0.0119 (12)−0.0077 (14)−0.0150 (15)
C130.0586 (17)0.0409 (15)0.0571 (18)−0.0022 (13)−0.0304 (15)−0.0072 (13)
C140.0517 (15)0.0404 (14)0.0353 (13)0.0042 (12)−0.0125 (11)−0.0020 (11)
C150.0309 (11)0.0343 (12)0.0440 (14)0.0076 (9)−0.0041 (10)−0.0053 (10)
C160.0514 (17)0.0582 (18)0.0611 (19)−0.0227 (14)0.0034 (14)−0.0093 (15)
N10.0300 (10)0.0308 (10)0.0375 (11)0.0019 (8)−0.0132 (8)−0.0031 (8)
N20.0386 (11)0.0300 (10)0.0450 (12)0.0034 (8)−0.0108 (9)−0.0038 (9)
N30.0448 (13)0.0524 (15)0.0716 (17)−0.0076 (11)−0.0076 (12)−0.0127 (12)
O10.0524 (11)0.0316 (9)0.0790 (14)0.0153 (8)−0.0330 (10)−0.0144 (9)
Geometric parameters (Å, º) top
C1—O11.203 (3)C9—H9B0.9600
C1—N11.407 (3)F1—H9C0.4086
C1—C21.454 (3)F2—H9A0.3969
C2—C71.378 (3)C10—C151.381 (4)
C2—C31.406 (3)C10—C111.400 (4)
C3—C41.382 (3)C10—N11.460 (3)
C3—H30.9300C11—C121.369 (4)
C4—N31.389 (3)C11—H110.9300
C4—C51.388 (4)C12—C131.375 (4)
C5—C61.403 (4)C12—H120.9300
C5—H50.9300C13—C141.363 (4)
C6—C71.381 (3)C13—H130.9300
C6—H60.9300C14—C151.393 (3)
C7—N21.412 (3)C14—H140.9300
C8—N21.274 (3)C15—C161.473 (4)
C8—N11.394 (3)C16—H16A0.9600
C8—C91.490 (3)C16—H16B0.9600
C9—F11.322 (4)C16—H16C0.9600
C9—F21.324 (5)N3—H3C0.8999
C9—H9A0.9601N3—H3A0.8599
C9—H9C0.9599
O1—C1—N1120.8 (2)C8—C9—H9B109.4
O1—C1—C2126.2 (2)H9A—C9—H9B109.5
N1—C1—C2113.00 (19)H9C—C9—H9B109.5
C7—C2—C3120.7 (2)C15—C10—C11122.9 (2)
C7—C2—C1120.6 (2)C15—C10—N1118.6 (2)
C3—C2—C1118.6 (2)C11—C10—N1118.5 (2)
C4—C3—C2119.8 (2)C12—C11—C10118.4 (3)
C4—C3—H3120.1C12—C11—H11120.8
C2—C3—H3120.1C10—C11—H11120.8
C3—C4—N3119.9 (2)C13—C12—C11120.1 (3)
C3—C4—C5119.1 (2)C13—C12—H12120.0
N3—C4—C5121.0 (2)C11—C12—H12120.0
C4—C5—C6121.3 (2)C14—C13—C12120.6 (3)
C4—C5—H5119.4C14—C13—H13119.7
C6—C5—H5119.4C12—C13—H13119.7
C7—C6—C5119.1 (2)C13—C14—C15122.0 (3)
C7—C6—H6120.5C13—C14—H14119.0
C5—C6—H6120.5C15—C14—H14119.0
C2—C7—C6120.1 (2)C10—C15—C14116.1 (2)
C2—C7—N2122.3 (2)C10—C15—C16122.7 (2)
C6—C7—N2117.5 (2)C14—C15—C16121.2 (2)
N2—C8—N1124.6 (2)C15—C16—H16A109.5
N2—C8—C9118.4 (2)C15—C16—H16B109.5
N1—C8—C9116.9 (2)H16A—C16—H16B109.5
F1—C9—F292.9 (3)C15—C16—H16C109.5
F1—C9—C8112.0 (3)H16A—C16—H16C109.5
F2—C9—C8116.1 (3)H16B—C16—H16C109.5
F1—C9—H9A100.1C8—N1—C1122.38 (19)
C8—C9—H9A109.5C8—N1—C10120.48 (18)
F2—C9—H9C102.1C1—N1—C10116.64 (18)
C8—C9—H9C109.5C8—N2—C7116.8 (2)
H9A—C9—H9C109.5C4—N3—H3C106.8
F1—C9—H9B115.9C4—N3—H3A119.8
F2—C9—H9B110.0H3C—N3—H3A107.3
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N3—H3A···O1i0.862.333.132 (3)155
N3—H3C···F2ii0.902.433.229 (4)147
C3—H3···O1i0.932.493.294 (3)145
Symmetry codes: (i) −x, −y+1, −z; (ii) x−1, −y+1/2, z−1/2.

Experimental details

Crystal data
Chemical formulaC16H14FN3O
Mr283.30
Crystal system, space groupMonoclinic, P21/c
Temperature (K)291
a, b, c (Å)6.3100 (13), 12.310 (3), 17.658 (4)
β (°) 90.24 (3)
V (Å3)1371.6 (5)
Z4
Radiation typeMo Kα
µ (mm−1)0.10
Crystal size (mm)0.30 × 0.26 × 0.24
Data collection
DiffractometerBruker SMART APEX CCD
Absorption correction–
No. of measured, independent and
observed [I > 2σ(I)] reflections		5223, 2691, 2172
Rint0.019
(sin θ/λ)max (Å−1)0.617
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.063, 0.154, 1.06
No. of reflections2691
No. of parameters200
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å−3)0.39, −0.36

Computer programs: SMART (Bruker, 2000), SAINT (Bruker, 2000), SAINT, SHELXTL (Bruker, 2000), SHELXTL.

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N3—H3A···O1i0.862.333.132 (3)155
N3—H3C···F2ii0.902.433.229 (4)147
C3—H3···O1i0.932.493.294 (3)145
Symmetry codes: (i) −x, −y+1, −z; (ii) x−1, −y+1/2, z−1/2.
 

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