supplementary materials


HTML versionpdf versioncif file3d viewstructure factorssupplementary materialsCIF check reportsimilar papers Open access

Acta Cryst. (2009). E65, o1015-o1016    [ doi:10.1107/S160053680901263X ]

1-[4-(Difluoromethoxy)phenyl]-N-(2,3-dimethylphenyl)-1H-1,2,4-triazole-3-carboxamide

Y.-G. Wang, G.-B. Huang and B.-C. Zhu

Abstract top

In the molecule of the title compound, C18H16F2N4O2, the 1,2,4-triazole ring forms dihedral angles of 3.6 (2) and 14.9 (6)° with the 4-difluoromethoxy-substituted benzene ring and the 2,3-dimethyl-substituted benzene ring, respectively. The OCHF2 group is twisted away from the plane of the benzene ring, as shown by the C-O-C-C torsion angle of 145.8 (2)°. The conformation is stabilized by an intermolecular N-H...N hydrogen bond. In the crystal, short C-H...O interactions lead to chains of molecules.

Comment top

1,2,4-Triazoles and their derivatives have long been known to exhibit diverse biological and pharmacological activities, such as antitubercular, anticancer (Vlasova et al., 1971; Kalluraya et al., 1996), anticonvulsant (Almasirad et al., 2004; Kanazawa et al., 1988; Chai et al., 2003; Hashimoto et al., 1990), anti-inflammatory (Labanauskas et al. ,2004), herbicidal, and analgesic properties (Tozkoparan et al., 2007; Amir & Shikha, 2004). Also, antifungal activity of aromatic ethers possessing a 1H-1,2,4-triazole ring has been reported (Wahbi et al., 1995). Herein, we report the synthesis and crystal structure of the title compound, (I).

In the molecule of the title compound (Fig. 1) the bond lengths and angles are generally within normal ranges. The planar 1,2,4-triazole ring is oriented at dihedral angles of 3.6 (2)° and 14.9 (6)° with respect to the 4-difluoromethoxy-substituted benzene ring and 2,3-dimethyl-substituted benzene ring, respectively. The CHF2 group is twisted away from the plane of the benzene ring, as shown by the C1—O1—C2—C3 torsion angle [145.8 (2)°].

Related literature top

For general background regarding the biological and pharmacological activities of 1,2,4-triazoles and their derivatives, see: Wahbi et al. (1995); Chai et al. (2003); Hashimoto et al. (1990); Kalluraya et al. (1996); Almasirad et al. (2004); Amir & Shikha (2004); Kanazawa et al. (1988); Vlasova et al. (1971); Labanauskas et al. (2004); Tozkoparan et al. (2007). For related syntheses, see: Drutkowski et al. (2002); Frohberg et al. (2002).

Experimental top

The general procedure to synthesize the title compound: 2-amine-N-(2,3-dimethyl-phenyl)-2-[(4-difluoromethoxy- phenyl)hydrazono]acetamide (10 mmol), 1.5 mL of a 37%-solution of formaldehyde (20 mmol) and 0.1 g p-toluene sulfonic acid were refluxed in approximately 50 mL ethanol. The reaction was complete after 10 h. The mixture was cooled to room temperature and the solvent was evaporated. The solid product was collected and recrystallized from 2-propanol (Drutkowski et al., 2002; Frohberg et al., 2002).

Refinement top

H atoms were placed in calculated positions with C—H = 0.95–0.99 Å, and refined in riding mode with Uiso(H) = 1.2Ueq(C).

Computing details top

Data collection: APEX2 (Bruker, 2004); cell refinement: SAINT (Bruker, 2004); data reduction: SAINT (Bruker, 2004); 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: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. View of the title compound showing the atom numbering scheme and the ellipsoids at the 50% probability level.
1-[4-(Difluoromethoxy)phenyl]-N-(2,3-dimethylphenyl)-1H-1,2,4- triazole-3-carboxamide top
Crystal data top
C18H16F2N4O2V = 839.28 (19) Å3
Mr = 358.35Z = 2
Triclinic, P1F(000) = 372
a = 7.5543 (10) ÅDx = 1.418 Mg m−3
b = 7.8132 (10) ÅMo Kα radiation, λ = 0.71073 Å
c = 14.8190 (19) ŵ = 0.11 mm−1
α = 95.974 (2)°T = 296 K
β = 98.593 (1)°Block, white
γ = 101.523 (1)°0.49 × 0.31 × 0.10 mm
Data collection top
Bruker APEXII CCD
diffractometer		3115 independent reflections
Radiation source: fine-focus sealed tube2366 reflections with I > 2σ(I)
graphiteRint = 0.017
φ and ω scansθmax = 25.5°, θmin = 2.7°
Absorption correction: multi-scan
(SADABS; Bruker, 2004)		h = −9→9
Tmin = 0.948, Tmax = 0.990k = −9→9
6446 measured reflectionsl = −17→17
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)] = 0.042H-atom parameters constrained
wR(F2) = 0.123 w = 1/[σ2(Fo2) + (0.0593P)2 + 0.1647P]
where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max < 0.001
3115 reflectionsΔρmax = 0.23 e Å−3
238 parametersΔρmin = −0.21 e Å−3
0 restraintsExtinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.016 (3)
Crystal data top
C18H16F2N4O2γ = 101.523 (1)°
Mr = 358.35V = 839.28 (19) Å3
Triclinic, P1Z = 2
a = 7.5543 (10) ÅMo Kα radiation
b = 7.8132 (10) ŵ = 0.11 mm−1
c = 14.8190 (19) ÅT = 296 K
α = 95.974 (2)°0.49 × 0.31 × 0.10 mm
β = 98.593 (1)°
Data collection top
Bruker APEXII CCD
diffractometer		3115 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2004)		2366 reflections with I > 2σ(I)
Tmin = 0.948, Tmax = 0.990Rint = 0.017
6446 measured reflectionsθmax = 25.5°
Refinement top
R[F2 > 2σ(F2)] = 0.042H-atom parameters constrained
wR(F2) = 0.123Δρmax = 0.23 e Å−3
S = 1.06Δρmin = −0.21 e Å−3
3115 reflectionsAbsolute structure: ?
238 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
F1−0.9182 (2)0.3392 (2)0.14577 (12)0.1146 (6)
F2−0.8560 (2)0.1332 (2)0.05859 (11)0.1113 (6)
O1−0.6301 (2)0.3298 (2)0.13688 (9)0.0742 (4)
O20.41124 (16)0.80678 (19)0.54210 (9)0.0634 (4)
N1−0.15235 (18)0.67315 (18)0.45595 (9)0.0458 (4)
N20.03287 (19)0.69741 (19)0.46115 (10)0.0472 (4)
N3−0.0355 (2)0.8275 (2)0.59091 (11)0.0663 (5)
N40.32482 (19)0.9655 (2)0.66010 (10)0.0513 (4)
H4D0.22850.99010.67790.062*
C1−0.7981 (3)0.2345 (3)0.13967 (17)0.0766 (7)
H1−0.79440.16320.19030.092*
C2−0.5184 (3)0.4106 (2)0.21999 (13)0.0541 (5)
C3−0.3332 (3)0.4212 (3)0.22448 (13)0.0611 (5)
H3−0.28990.37080.17490.073*
C4−0.2118 (3)0.5063 (3)0.30237 (13)0.0556 (5)
H4−0.08660.51300.30570.067*
C5−0.2770 (2)0.5815 (2)0.37546 (11)0.0444 (4)
C6−0.4633 (2)0.5707 (2)0.37090 (13)0.0539 (5)
H6−0.50690.62120.42030.065*
C7−0.5839 (3)0.4846 (3)0.29260 (13)0.0577 (5)
H7−0.70930.47680.28910.069*
C8−0.1882 (3)0.7512 (3)0.53408 (14)0.0649 (6)
H8−0.30530.75130.54640.078*
C90.0950 (2)0.7909 (2)0.54299 (11)0.0460 (4)
C100.2942 (2)0.8537 (2)0.58047 (11)0.0448 (4)
C110.4936 (2)1.0475 (2)0.71818 (12)0.0464 (4)
C120.6569 (2)1.0709 (2)0.68418 (13)0.0538 (5)
H120.65751.03100.62290.065*
C130.8177 (3)1.1539 (3)0.74204 (14)0.0599 (5)
H130.92801.16820.72000.072*
C140.8166 (3)1.2157 (3)0.83215 (14)0.0629 (5)
H140.92661.27130.87040.076*
C150.6546 (3)1.1965 (3)0.86695 (13)0.0572 (5)
C160.4892 (2)1.1100 (2)0.80967 (12)0.0506 (4)
C170.6597 (3)1.2699 (3)0.96572 (15)0.0823 (7)
H17A0.78401.32310.99410.124*
H17B0.61181.17620.99840.124*
H17C0.58641.35700.96750.124*
C180.3094 (3)1.0884 (3)0.84471 (14)0.0703 (6)
H18A0.24201.17060.82080.105*
H18B0.33301.11050.91080.105*
H18C0.23890.97030.82480.105*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0681 (9)0.1287 (13)0.1263 (13)0.0247 (9)−0.0216 (9)−0.0270 (10)
F20.1052 (12)0.1003 (11)0.0926 (11)−0.0021 (9)−0.0311 (9)−0.0318 (8)
O10.0631 (9)0.0896 (11)0.0523 (8)0.0000 (8)−0.0083 (7)−0.0111 (7)
O20.0403 (7)0.0849 (10)0.0585 (8)0.0131 (7)0.0075 (6)−0.0162 (7)
N10.0359 (8)0.0537 (8)0.0444 (8)0.0091 (6)0.0045 (6)−0.0034 (6)
N20.0356 (8)0.0569 (9)0.0460 (8)0.0084 (6)0.0055 (6)−0.0017 (7)
N30.0412 (9)0.0964 (13)0.0542 (10)0.0167 (8)0.0046 (7)−0.0201 (9)
N40.0378 (8)0.0640 (10)0.0482 (9)0.0110 (7)0.0053 (6)−0.0065 (7)
C10.0699 (15)0.0672 (14)0.0725 (15)0.0012 (12)−0.0212 (11)−0.0079 (11)
C20.0521 (11)0.0548 (11)0.0466 (10)0.0044 (8)−0.0037 (8)−0.0005 (8)
C30.0570 (12)0.0698 (13)0.0502 (11)0.0090 (10)0.0090 (9)−0.0105 (9)
C40.0431 (10)0.0625 (11)0.0562 (11)0.0076 (8)0.0075 (8)−0.0050 (9)
C50.0410 (9)0.0456 (9)0.0425 (9)0.0072 (7)0.0015 (7)0.0009 (7)
C60.0436 (10)0.0648 (12)0.0495 (11)0.0138 (9)0.0027 (8)−0.0050 (9)
C70.0410 (10)0.0693 (12)0.0582 (12)0.0123 (9)−0.0005 (8)−0.0001 (9)
C80.0379 (10)0.0943 (15)0.0557 (11)0.0151 (10)0.0055 (8)−0.0180 (10)
C90.0397 (9)0.0541 (10)0.0428 (9)0.0117 (8)0.0056 (7)−0.0004 (8)
C100.0396 (9)0.0511 (10)0.0421 (9)0.0100 (7)0.0054 (7)0.0012 (7)
C110.0413 (9)0.0497 (10)0.0451 (10)0.0091 (7)0.0030 (7)0.0013 (8)
C120.0469 (10)0.0614 (11)0.0496 (10)0.0084 (8)0.0078 (8)−0.0010 (8)
C130.0433 (10)0.0661 (12)0.0638 (12)0.0047 (9)0.0059 (9)−0.0008 (10)
C140.0485 (11)0.0651 (12)0.0638 (13)0.0056 (9)−0.0084 (9)−0.0033 (10)
C150.0601 (12)0.0597 (11)0.0472 (10)0.0145 (9)−0.0024 (9)0.0008 (9)
C160.0514 (10)0.0557 (11)0.0436 (10)0.0150 (8)0.0037 (8)0.0018 (8)
C170.0873 (17)0.0976 (18)0.0509 (12)0.0169 (14)−0.0047 (11)−0.0101 (11)
C180.0616 (13)0.0961 (16)0.0510 (12)0.0169 (11)0.0128 (10)−0.0033 (11)
Geometric parameters (Å, °) top
F1—C11.345 (3)C6—C71.381 (2)
F2—C11.330 (3)C6—H60.9300
O1—C11.346 (3)C7—H70.9300
O1—C21.394 (2)C8—H80.9300
O2—C101.215 (2)C9—C101.487 (2)
N1—C81.341 (2)C11—C121.387 (2)
N1—N21.3632 (19)C11—C161.400 (2)
N1—C51.428 (2)C12—C131.374 (3)
N2—C91.316 (2)C12—H120.9300
N3—C81.314 (2)C13—C141.374 (3)
N3—C91.355 (2)C13—H130.9300
N4—C101.353 (2)C14—C151.385 (3)
N4—C111.417 (2)C14—H140.9300
N4—H4D0.8600C15—C161.402 (3)
C1—H10.9800C15—C171.507 (3)
C2—C71.372 (3)C16—C181.510 (3)
C2—C31.376 (3)C17—H17A0.9600
C3—C41.377 (3)C17—H17B0.9600
C3—H30.9300C17—H17C0.9600
C4—C51.380 (2)C18—H18A0.9600
C4—H40.9300C18—H18B0.9600
C5—C61.384 (2)C18—H18C0.9600
C1—O1—C2118.10 (17)N2—C9—N3115.33 (15)
C8—N1—N2109.18 (14)N2—C9—C10122.68 (15)
C8—N1—C5129.19 (15)N3—C9—C10121.99 (15)
N2—N1—C5121.60 (13)O2—C10—N4125.87 (16)
C9—N2—N1102.16 (13)O2—C10—C9122.19 (15)
C8—N3—C9102.47 (15)N4—C10—C9111.94 (14)
C10—N4—C11129.00 (15)C12—C11—C16121.23 (16)
C10—N4—H4D115.5C12—C11—N4120.80 (16)
C11—N4—H4D115.5C16—C11—N4117.93 (15)
F2—C1—F1105.50 (18)C13—C12—C11119.26 (17)
F2—C1—O1106.7 (2)C13—C12—H12120.4
F1—C1—O1110.9 (2)C11—C12—H12120.4
F2—C1—H1111.2C14—C13—C12120.48 (18)
F1—C1—H1111.2C14—C13—H13119.8
O1—C1—H1111.2C12—C13—H13119.8
C7—C2—C3120.57 (17)C13—C14—C15121.14 (18)
C7—C2—O1123.26 (18)C13—C14—H14119.4
C3—C2—O1116.09 (17)C15—C14—H14119.4
C2—C3—C4120.04 (18)C14—C15—C16119.45 (18)
C2—C3—H3120.0C14—C15—C17119.27 (19)
C4—C3—H3120.0C16—C15—C17121.28 (19)
C3—C4—C5119.59 (18)C11—C16—C15118.43 (17)
C3—C4—H4120.2C11—C16—C18120.51 (16)
C5—C4—H4120.2C15—C16—C18121.04 (17)
C4—C5—C6120.32 (16)C15—C17—H17A109.5
C4—C5—N1120.17 (15)C15—C17—H17B109.5
C6—C5—N1119.50 (15)H17A—C17—H17B109.5
C7—C6—C5119.65 (17)C15—C17—H17C109.5
C7—C6—H6120.2H17A—C17—H17C109.5
C5—C6—H6120.2H17B—C17—H17C109.5
C2—C7—C6119.82 (18)C16—C18—H18A109.5
C2—C7—H7120.1C16—C18—H18B109.5
C6—C7—H7120.1H18A—C18—H18B109.5
N3—C8—N1110.85 (16)C16—C18—H18C109.5
N3—C8—H8124.6H18A—C18—H18C109.5
N1—C8—H8124.6H18B—C18—H18C109.5
C8—N1—N2—C9−0.5 (2)C8—N3—C9—N2−0.1 (2)
C5—N1—N2—C9177.77 (15)C8—N3—C9—C10179.36 (18)
C2—O1—C1—F2−162.99 (17)C11—N4—C10—O2−2.5 (3)
C2—O1—C1—F182.6 (2)C11—N4—C10—C9177.38 (16)
C1—O1—C2—C7−37.5 (3)N2—C9—C10—O2−8.1 (3)
C1—O1—C2—C3145.8 (2)N3—C9—C10—O2172.46 (18)
C7—C2—C3—C40.1 (3)N2—C9—C10—N4172.08 (16)
O1—C2—C3—C4176.96 (18)N3—C9—C10—N4−7.4 (2)
C2—C3—C4—C5−0.4 (3)C10—N4—C11—C1222.9 (3)
C3—C4—C5—C60.4 (3)C10—N4—C11—C16−159.57 (17)
C3—C4—C5—N1−178.75 (17)C16—C11—C12—C131.4 (3)
C8—N1—C5—C4−178.5 (2)N4—C11—C12—C13178.84 (17)
N2—N1—C5—C43.6 (2)C11—C12—C13—C14−1.1 (3)
C8—N1—C5—C62.4 (3)C12—C13—C14—C15−0.1 (3)
N2—N1—C5—C6−175.54 (16)C13—C14—C15—C161.1 (3)
C4—C5—C6—C7−0.2 (3)C13—C14—C15—C17−178.7 (2)
N1—C5—C6—C7178.98 (16)C12—C11—C16—C15−0.4 (3)
C3—C2—C7—C60.1 (3)N4—C11—C16—C15−177.95 (16)
O1—C2—C7—C6−176.50 (17)C12—C11—C16—C18178.06 (18)
C5—C6—C7—C2−0.1 (3)N4—C11—C16—C180.5 (3)
C9—N3—C8—N1−0.2 (2)C14—C15—C16—C11−0.8 (3)
N2—N1—C8—N30.5 (2)C17—C15—C16—C11178.95 (19)
C5—N1—C8—N3−177.64 (17)C14—C15—C16—C18−179.26 (19)
N1—N2—C9—N30.4 (2)C17—C15—C16—C180.5 (3)
N1—N2—C9—C10−179.09 (15)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N4—H4D···N30.862.272.717 (2)113
C6—H6···O2i0.932.433.344 (2)169
C8—H8···O2i0.932.263.159 (2)162
Symmetry codes: (i) x−1, y, z.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N4—H4D···N30.862.272.717 (2)113
C6—H6···O2i0.932.433.344 (2)169
C8—H8···O2i0.932.263.159 (2)162
Symmetry codes: (i) x−1, y, z.
Acknowledgements top

The authors are grateful for the financial support of the Education Office Foundation of Zhejiang Province (project No. Y200803795).

references
References top

Almasirad, A., Tabatabai, S. A., Faizi, M., Kebriaeezadeh, A., Mehrabi, N., Dalvandi, A. & Shafiee, A. (2004). Bioorg. Med. Chem. Lett. 14, 6057–6059.

Amir, M. & Shikha, K. (2004). Eur. J. Med. Chem. 39, 535–545.

Bruker (2004). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.

Chai, B., Qian, X., Cao, S., Liu, H. & Song, G. (2003). Arkivoc. ii, 141–145.

Drutkowski, G., Donner, Ch., Schulze, I. & Frohberg, P. (2002). Tetrahedron, 58, 5317–5326.

Frohberg, P., Drutkowski, G. & Wagner, Ch. (2002). Eur. J. Org. Chem. pp. 1654–1663.

Hashimoto, F., Sugimoto, C. & Hayashi, H. (1990). Chem. Pharm. Bull. 38, 2532–2536.

Kalluraya, B., Shetty, S. N., Gunaga, P. & Holla, B. S. (1996). Boll. Chim. Farm. 135, 638–642.

Kanazawa, S., Driscoll, M. & Struhl, K. (1988). Mol. Cell. Biol. 8, 644–673.

Labanauskas, L., Udrenaite, E., Gaidelis, P. & Brukštus, A. (2004). Farmaco, 59, 255–259.

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

Spek, A. L. (2009). Acta Cryst. D65, 148–155.

Tozkoparan, B., Küpeli, E., Yeşilada, E. & Ertan, M. (2007). Bioorg. Med. Chem. 15, 1808–1814.

Vlasova, L. A., Shamaeva, E. M., Afanaséva, G. B. & Postvskii, I. Y. (1971). Pharm. Chem. J. 5, 473–477.

Wahbi, Y., Caujolle, R., Tournaire, C., Payard, M., Linas, M. D. & Seguela, J. P. (1995). Eur. J. Med. Chem. 30, 955–962.