Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807026670/xu2266sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807026670/xu2266Isup2.hkl |
CCDC reference: 654878
Key indicators
- Single-crystal X-ray study
- T = 291 K
- Mean (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
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%.
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.
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).
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.
Fig. 1. The molecular structure of (I) (thermal ellipsoids are shown at 30% probability levels). | |
Fig. 2. A packing diagram for (I) (Dashed lines indicate hydrogen bonds). |
C16H14FN3O | F(000) = 592 |
Mr = 283.30 | Dx = 1.372 Mg m−3 |
Monoclinic, P21/c | Melting point: 470 K |
Hall symbol: -P 2ybc | Mo Kα radiation, λ = 0.71073 Å |
a = 6.3100 (13) Å | Cell parameters from 732 reflections |
b = 12.310 (3) Å | θ = 2.1–25.5° |
c = 17.658 (4) Å | µ = 0.10 mm−1 |
β = 90.24 (3)° | T = 291 K |
V = 1371.6 (5) Å3 | Block, yellow |
Z = 4 | 0.30 × 0.26 × 0.24 mm |
Bruker SMART APEX CCD diffractometer | 2172 reflections with I > 2σ(I) |
Radiation source: sealed tube | Rint = 0.019 |
Graphite monochromator | θmax = 26.0°, θmin = 2.0° |
φ and ω scans | h = −7→7 |
5223 measured reflections | k = −15→15 |
2691 independent reflections | l = −21→21 |
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)] = 0.063 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.154 | H-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 parameters | Δρmax = 0.39 e Å−3 |
0 restraints | Δρmin = −0.36 e Å−3 |
C16H14FN3O | V = 1371.6 (5) Å3 |
Mr = 283.30 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 6.3100 (13) Å | µ = 0.10 mm−1 |
b = 12.310 (3) Å | T = 291 K |
c = 17.658 (4) Å | 0.30 × 0.26 × 0.24 mm |
β = 90.24 (3)° |
Bruker SMART APEX CCD diffractometer | 2172 reflections with I > 2σ(I) |
5223 measured reflections | Rint = 0.019 |
2691 independent reflections |
R[F2 > 2σ(F2)] = 0.063 | 0 restraints |
wR(F2) = 0.154 | H-atom parameters constrained |
S = 1.06 | Δρmax = 0.39 e Å−3 |
2691 reflections | Δρmin = −0.36 e Å−3 |
200 parameters |
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. |
x | y | z | Uiso*/Ueq | Occ. (<1) | |
C1 | 0.3272 (4) | 0.37992 (19) | 0.06660 (14) | 0.0351 (5) | |
C2 | 0.2262 (3) | 0.29811 (18) | 0.01924 (13) | 0.0311 (5) | |
C3 | 0.0418 (4) | 0.3265 (2) | −0.02108 (14) | 0.0378 (6) | |
H3 | −0.0084 | 0.3975 | −0.0197 | 0.045* | |
C4 | −0.0646 (4) | 0.2485 (2) | −0.06276 (14) | 0.0395 (6) | |
C5 | 0.0130 (4) | 0.1430 (2) | −0.06377 (14) | 0.0435 (6) | |
H5 | −0.0587 | 0.0902 | −0.0914 | 0.052* | |
C6 | 0.1975 (4) | 0.1146 (2) | −0.02386 (14) | 0.0403 (6) | |
H6 | 0.2497 | 0.0440 | −0.0259 | 0.048* | |
C7 | 0.3005 (4) | 0.19287 (19) | 0.01852 (13) | 0.0333 (5) | |
C8 | 0.5704 (4) | 0.23229 (19) | 0.10110 (13) | 0.0334 (5) | |
C9 | 0.7671 (5) | 0.2024 (2) | 0.14313 (18) | 0.0559 (8) | |
H9A | 0.7379 | 0.1994 | 0.1964 | 0.067* | 0.50 |
H9C | 0.8160 | 0.1327 | 0.1262 | 0.067* | 0.50 |
H9B | 0.8744 | 0.2560 | 0.1338 | 0.067* | |
F1 | 0.8229 (5) | 0.1004 (3) | 0.1308 (2) | 0.0569 (9) | 0.50 |
F2 | 0.7462 (5) | 0.1867 (3) | 0.21687 (18) | 0.0554 (8) | 0.50 |
C10 | 0.5861 (3) | 0.40942 (19) | 0.16752 (14) | 0.0346 (6) | |
C11 | 0.7616 (4) | 0.4745 (2) | 0.15056 (15) | 0.0425 (6) | |
H11 | 0.8214 | 0.4735 | 0.1025 | 0.051* | |
C12 | 0.8429 (4) | 0.5396 (2) | 0.20645 (19) | 0.0557 (8) | |
H12 | 0.9575 | 0.5847 | 0.1962 | 0.067* | |
C13 | 0.7555 (5) | 0.5383 (2) | 0.27761 (17) | 0.0523 (8) | |
H13 | 0.8140 | 0.5810 | 0.3158 | 0.063* | |
C14 | 0.5837 (4) | 0.4750 (2) | 0.29274 (15) | 0.0425 (6) | |
H14 | 0.5252 | 0.4767 | 0.3410 | 0.051* | |
C15 | 0.4929 (4) | 0.4076 (2) | 0.23813 (14) | 0.0364 (5) | |
C16 | 0.3045 (5) | 0.3415 (3) | 0.25512 (18) | 0.0569 (8) | |
H16A | 0.1814 | 0.3747 | 0.2329 | 0.085* | |
H16B | 0.2867 | 0.3367 | 0.3090 | 0.085* | |
H16C | 0.3225 | 0.2699 | 0.2346 | 0.085* | |
N1 | 0.5001 (3) | 0.33912 (16) | 0.10830 (11) | 0.0328 (5) | |
N2 | 0.4853 (3) | 0.16129 (16) | 0.05817 (12) | 0.0379 (5) | |
N3 | −0.2479 (4) | 0.2761 (2) | −0.10214 (15) | 0.0563 (7) | |
H3C | −0.2256 | 0.2587 | −0.1510 | 0.068* | |
H3A | −0.2934 | 0.3419 | −0.1011 | 0.068* | |
O1 | 0.2752 (3) | 0.47363 (14) | 0.07204 (12) | 0.0544 (6) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0318 (12) | 0.0284 (12) | 0.0451 (14) | 0.0018 (9) | −0.0125 (10) | −0.0001 (10) |
C2 | 0.0304 (11) | 0.0321 (12) | 0.0309 (11) | 0.0006 (9) | −0.0084 (9) | 0.0007 (9) |
C3 | 0.0352 (12) | 0.0393 (13) | 0.0389 (13) | 0.0000 (10) | −0.0164 (10) | 0.0014 (10) |
C4 | 0.0374 (13) | 0.0440 (14) | 0.0369 (13) | −0.0099 (11) | −0.0137 (10) | 0.0058 (11) |
C5 | 0.0550 (16) | 0.0387 (14) | 0.0365 (13) | −0.0176 (12) | −0.0145 (11) | −0.0029 (11) |
C6 | 0.0457 (14) | 0.0305 (12) | 0.0447 (14) | −0.0049 (11) | −0.0105 (11) | −0.0040 (10) |
C7 | 0.0303 (11) | 0.0342 (12) | 0.0352 (12) | −0.0017 (9) | −0.0002 (9) | 0.0016 (10) |
C8 | 0.0276 (11) | 0.0389 (13) | 0.0338 (12) | 0.0036 (9) | −0.0015 (9) | −0.0023 (10) |
C9 | 0.0507 (17) | 0.0490 (16) | 0.068 (2) | 0.0209 (13) | −0.0260 (15) | −0.0128 (14) |
F1 | 0.0510 (18) | 0.0493 (19) | 0.070 (2) | −0.0051 (15) | −0.0137 (16) | −0.0006 (16) |
F2 | 0.0490 (18) | 0.069 (2) | 0.0482 (19) | −0.0034 (16) | −0.0059 (15) | −0.0051 (16) |
C10 | 0.0257 (11) | 0.0329 (12) | 0.0450 (14) | 0.0122 (9) | −0.0143 (10) | −0.0088 (10) |
C11 | 0.0417 (14) | 0.0442 (14) | 0.0416 (14) | −0.0082 (11) | −0.0028 (11) | −0.0052 (11) |
C12 | 0.0375 (14) | 0.0478 (16) | 0.082 (2) | −0.0119 (12) | −0.0077 (14) | −0.0150 (15) |
C13 | 0.0586 (17) | 0.0409 (15) | 0.0571 (18) | −0.0022 (13) | −0.0304 (15) | −0.0072 (13) |
C14 | 0.0517 (15) | 0.0404 (14) | 0.0353 (13) | 0.0042 (12) | −0.0125 (11) | −0.0020 (11) |
C15 | 0.0309 (11) | 0.0343 (12) | 0.0440 (14) | 0.0076 (9) | −0.0041 (10) | −0.0053 (10) |
C16 | 0.0514 (17) | 0.0582 (18) | 0.0611 (19) | −0.0227 (14) | 0.0034 (14) | −0.0093 (15) |
N1 | 0.0300 (10) | 0.0308 (10) | 0.0375 (11) | 0.0019 (8) | −0.0132 (8) | −0.0031 (8) |
N2 | 0.0386 (11) | 0.0300 (10) | 0.0450 (12) | 0.0034 (8) | −0.0108 (9) | −0.0038 (9) |
N3 | 0.0448 (13) | 0.0524 (15) | 0.0716 (17) | −0.0076 (11) | −0.0076 (12) | −0.0127 (12) |
O1 | 0.0524 (11) | 0.0316 (9) | 0.0790 (14) | 0.0153 (8) | −0.0330 (10) | −0.0144 (9) |
C1—O1 | 1.203 (3) | C9—H9B | 0.9600 |
C1—N1 | 1.407 (3) | F1—H9C | 0.4086 |
C1—C2 | 1.454 (3) | F2—H9A | 0.3969 |
C2—C7 | 1.378 (3) | C10—C15 | 1.381 (4) |
C2—C3 | 1.406 (3) | C10—C11 | 1.400 (4) |
C3—C4 | 1.382 (3) | C10—N1 | 1.460 (3) |
C3—H3 | 0.9300 | C11—C12 | 1.369 (4) |
C4—N3 | 1.389 (3) | C11—H11 | 0.9300 |
C4—C5 | 1.388 (4) | C12—C13 | 1.375 (4) |
C5—C6 | 1.403 (4) | C12—H12 | 0.9300 |
C5—H5 | 0.9300 | C13—C14 | 1.363 (4) |
C6—C7 | 1.381 (3) | C13—H13 | 0.9300 |
C6—H6 | 0.9300 | C14—C15 | 1.393 (3) |
C7—N2 | 1.412 (3) | C14—H14 | 0.9300 |
C8—N2 | 1.274 (3) | C15—C16 | 1.473 (4) |
C8—N1 | 1.394 (3) | C16—H16A | 0.9600 |
C8—C9 | 1.490 (3) | C16—H16B | 0.9600 |
C9—F1 | 1.322 (4) | C16—H16C | 0.9600 |
C9—F2 | 1.324 (5) | N3—H3C | 0.8999 |
C9—H9A | 0.9601 | N3—H3A | 0.8599 |
C9—H9C | 0.9599 | ||
O1—C1—N1 | 120.8 (2) | C8—C9—H9B | 109.4 |
O1—C1—C2 | 126.2 (2) | H9A—C9—H9B | 109.5 |
N1—C1—C2 | 113.00 (19) | H9C—C9—H9B | 109.5 |
C7—C2—C3 | 120.7 (2) | C15—C10—C11 | 122.9 (2) |
C7—C2—C1 | 120.6 (2) | C15—C10—N1 | 118.6 (2) |
C3—C2—C1 | 118.6 (2) | C11—C10—N1 | 118.5 (2) |
C4—C3—C2 | 119.8 (2) | C12—C11—C10 | 118.4 (3) |
C4—C3—H3 | 120.1 | C12—C11—H11 | 120.8 |
C2—C3—H3 | 120.1 | C10—C11—H11 | 120.8 |
C3—C4—N3 | 119.9 (2) | C13—C12—C11 | 120.1 (3) |
C3—C4—C5 | 119.1 (2) | C13—C12—H12 | 120.0 |
N3—C4—C5 | 121.0 (2) | C11—C12—H12 | 120.0 |
C4—C5—C6 | 121.3 (2) | C14—C13—C12 | 120.6 (3) |
C4—C5—H5 | 119.4 | C14—C13—H13 | 119.7 |
C6—C5—H5 | 119.4 | C12—C13—H13 | 119.7 |
C7—C6—C5 | 119.1 (2) | C13—C14—C15 | 122.0 (3) |
C7—C6—H6 | 120.5 | C13—C14—H14 | 119.0 |
C5—C6—H6 | 120.5 | C15—C14—H14 | 119.0 |
C2—C7—C6 | 120.1 (2) | C10—C15—C14 | 116.1 (2) |
C2—C7—N2 | 122.3 (2) | C10—C15—C16 | 122.7 (2) |
C6—C7—N2 | 117.5 (2) | C14—C15—C16 | 121.2 (2) |
N2—C8—N1 | 124.6 (2) | C15—C16—H16A | 109.5 |
N2—C8—C9 | 118.4 (2) | C15—C16—H16B | 109.5 |
N1—C8—C9 | 116.9 (2) | H16A—C16—H16B | 109.5 |
F1—C9—F2 | 92.9 (3) | C15—C16—H16C | 109.5 |
F1—C9—C8 | 112.0 (3) | H16A—C16—H16C | 109.5 |
F2—C9—C8 | 116.1 (3) | H16B—C16—H16C | 109.5 |
F1—C9—H9A | 100.1 | C8—N1—C1 | 122.38 (19) |
C8—C9—H9A | 109.5 | C8—N1—C10 | 120.48 (18) |
F2—C9—H9C | 102.1 | C1—N1—C10 | 116.64 (18) |
C8—C9—H9C | 109.5 | C8—N2—C7 | 116.8 (2) |
H9A—C9—H9C | 109.5 | C4—N3—H3C | 106.8 |
F1—C9—H9B | 115.9 | C4—N3—H3A | 119.8 |
F2—C9—H9B | 110.0 | H3C—N3—H3A | 107.3 |
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H3A···O1i | 0.86 | 2.33 | 3.132 (3) | 155 |
N3—H3C···F2ii | 0.90 | 2.43 | 3.229 (4) | 147 |
C3—H3···O1i | 0.93 | 2.49 | 3.294 (3) | 145 |
Symmetry codes: (i) −x, −y+1, −z; (ii) x−1, −y+1/2, z−1/2. |
Experimental details
Crystal data | |
Chemical formula | C16H14FN3O |
Mr | 283.30 |
Crystal system, space group | Monoclinic, 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) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.10 |
Crystal size (mm) | 0.30 × 0.26 × 0.24 |
Data collection | |
Diffractometer | Bruker SMART APEX CCD |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 5223, 2691, 2172 |
Rint | 0.019 |
(sin θ/λ)max (Å−1) | 0.617 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.063, 0.154, 1.06 |
No. of reflections | 2691 |
No. of parameters | 200 |
H-atom treatment | H-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.
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H3A···O1i | 0.86 | 2.33 | 3.132 (3) | 155 |
N3—H3C···F2ii | 0.90 | 2.43 | 3.229 (4) | 147 |
C3—H3···O1i | 0.93 | 2.49 | 3.294 (3) | 145 |
Symmetry codes: (i) −x, −y+1, −z; (ii) x−1, −y+1/2, z−1/2. |
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.