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Acta Crystallogr Sect E Struct Rep Online. 2009 June 1; 65(Pt 6): o1231.
Published online 2009 May 7. doi:  10.1107/S1600536809016250
PMCID: PMC2969777

3-(3-Chloro­anilino)-1-(3,5-dimethyl-1H-pyrazol-1-yl)propan-1-one

Abstract

In the mol­ecule of the title compound, C14H16ClN3O, the benzene and pyrazole rings are oriented at a dihedral angle of 3.50 (3)°. In the crystal structure, inter­molecular N—H(...)O hydrogen bonds link the mol­ecules into chains. A π–π contact between the benzene and pyrazole rings [centroid–centroid distance = 3.820 (3) Å] may further stabilize the structure.

Related literature

For general background to 1,3,5-tris­ubstituted pyrazoles, see: Elguero & Goya (2002 [triangle]). The pyrazole chemotype is the structural motif of several highly potent inhibitors against coagulation factor Xa, see: Penning & Talley (1997 [triangle]); Eriksson & Quinlan (2006 [triangle]); Escolar et al. (2006 [triangle]). Pyrazole 3-carboxyl­ates have been identified as selective antagonist subtype 1PGE2 receptors (Akarca, 2005 [triangle]) and pyrazole-based mat­erials have been used as co-polymers for electroluminescent applications (Mella & Fagnoni, 1997 [triangle]). For the synthesis, see: Saeed & Mumtaz (2008 [triangle]). For bond-length data, see: Allen et al. (1987 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o1231-scheme1.jpg

Experimental

Crystal data

  • C14H16ClN3O
  • M r = 277.75
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o1231-efi1.jpg
  • a = 14.5389 (8) Å
  • b = 7.8731 (6) Å
  • c = 12.1411 (7) Å
  • β = 102.566 (5)°
  • V = 1356.46 (15) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.28 mm−1
  • T = 173 K
  • 0.35 × 0.33 × 0.33 mm

Data collection

  • Stoe IPDS II two-circle diffractometer
  • Absorption correction: multi-scan (MULABS; Blessing, 1995 [triangle]) T min = 0.909, T max = 0.914
  • 8907 measured reflections
  • 2528 independent reflections
  • 2192 reflections with I > 2σ(I)
  • R int = 0.034

Refinement

  • R[F 2 > 2σ(F 2)] = 0.031
  • wR(F 2) = 0.086
  • S = 1.06
  • 2528 reflections
  • 179 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.22 e Å−3
  • Δρmin = −0.23 e Å−3

Data collection: X-AREA (Stoe & Cie, 2001 [triangle]); cell refinement: X-RED (Stoe & Cie, 2001 [triangle]); data reduction: X-RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: PLATON (Spek, 2009 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809016250/hk2680sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809016250/hk2680Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

AS gratefully acknowledges a research grant from Quaid-i-Azam University, Islamabad, under the URF project No. DFNS/2009-36.

supplementary crystallographic information

Comment

1,3,5-Trisubstituted pyrazoles are synthetic targets of paramount significance in the pharmacological industry, in view of the fact that such a heterocyclic moiety represents the core structure of numerous drugs including the widely prescribed Celebrex and Viagra (Elguero & Goya, 2002). Pyrazole chemotype is structural motif of several highly potent inhibitors against coagulation factor Xa (Penning & Talley, 1997) among them Rivaroxaban (Eriksson & Quinlan, 2006) and Apixaban (Escolar et al., 2006) were selected for clinical development for the prevention and treatment of thrombotic diseases. Pyrazole 3-carboxylates were also identified as selective antagonist subtype 1PGE2 receptors (Akarca, 2005). The pyrazole-based materials have been used as co-polymers for electroluminescent applications (Mella & Fagnoni, 1997). We report herein the crystal structure of the title compound.

In the molecule of the title compound (Fig 1), the bond lengths (Allen et al., 1987) and angles are within normal ranges. Rings A (C11-C16) and B (N21/N22/C23-C25) are, of course, planar, and they are oriented at a dihedral angle of A/B = 3.50 (3)°.

In the crystal structure, intermolecular N-H···O hydrogen bonds (Table 1) link the molecules into chains (Fig. 2), in which they may be effective in the stabilization of the structure. The π–π contact between the phenyl ring and the pyrazole ring, Cg1—Cg2i [symmetry code: (i) 1 - x, 1 - y, -z, where Cg1 and Cg2 are centroids of the rings A (C11-C16) and B (N21/N22/C23-C25), respectively] may further stabilize the structure, with centroid-centroid distance of 3.820 (3) Å.

Experimental

The title compound was prepared by cyclocondensation of pentane-2,4-dione with corresponding 3-(3-Chlorophenylamino) propionohydrazide according to a method reported earlier (Saeed & Mumtaz, 2008). Recrystallization from methanol afforded the title compound (yield; 81%). Anal. calcd. for C14H16ClN3O: C, 60.54; H, 5.81; N, 15.13%; found: C, 60.51; H, 5.83; N, 15.07%.

Refinement

H atom of NH group was located in difference Fourier map and refined isotropically. The remaining H atoms were positioned geometrically with C-H = 0.95, 0.99 and 0.98 Å, for aromatic, methylene and methyl H atoms, respectively, and constrained to ride on their parent atoms, with Uiso(H) = xUeq(C), where x = 1.5 for methyl H and x = 1.2 for all other H atoms.

Figures

Fig. 1.
The molecular structure of the title molecule, with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
Fig. 2.
A partial packing diagram of the title compound. Hydrogen bonds are shown as dashed lines.

Crystal data

C14H16ClN3OF(000) = 584
Mr = 277.75Dx = 1.360 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 8296 reflections
a = 14.5389 (8) Åθ = 3.5–25.9°
b = 7.8731 (6) ŵ = 0.28 mm1
c = 12.1411 (7) ÅT = 173 K
β = 102.566 (5)°Block, orange
V = 1356.46 (15) Å30.35 × 0.33 × 0.33 mm
Z = 4

Data collection

Stoe IPDS II two-circle diffractometer2528 independent reflections
Radiation source: fine-focus sealed tube2192 reflections with I > 2σ(I)
graphiteRint = 0.034
ω scansθmax = 25.6°, θmin = 3.4°
Absorption correction: multi-scan (MULABS; Blessing, 1995)h = −17→16
Tmin = 0.909, Tmax = 0.914k = −9→8
8907 measured reflectionsl = −14→14

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.031H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.086w = 1/[σ2(Fo2) + (0.0525P)2 + 0.155P] where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max < 0.001
2528 reflectionsΔρmax = 0.22 e Å3
179 parametersΔρmin = −0.23 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0118 (15)

Special details

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)

xyzUiso*/Ueq
Cl10.09245 (2)0.19275 (5)0.40578 (3)0.03790 (14)
O10.56854 (7)0.37061 (15)0.32982 (8)0.0338 (3)
N10.44533 (8)0.16939 (17)0.58746 (10)0.0303 (3)
H10.4841 (13)0.165 (2)0.6485 (15)0.035 (4)*
C10.47221 (8)0.24939 (17)0.49191 (10)0.0230 (3)
H1A0.44580.36560.48100.028*
H1B0.44780.18310.42240.028*
C20.57897 (9)0.25608 (17)0.51596 (10)0.0224 (3)
H2A0.60190.32360.58530.027*
H2B0.60410.13940.53040.027*
C30.61688 (9)0.33260 (16)0.42090 (10)0.0218 (3)
C110.35323 (9)0.13937 (17)0.59318 (10)0.0224 (3)
C120.27731 (9)0.18284 (17)0.50608 (10)0.0232 (3)
H120.28730.24070.44100.028*
C130.18671 (9)0.13994 (18)0.51620 (11)0.0261 (3)
C140.16813 (10)0.0571 (2)0.60922 (12)0.0319 (3)
H140.10560.02810.61350.038*
C150.24443 (10)0.01754 (19)0.69646 (12)0.0321 (3)
H150.2337−0.03780.76200.039*
C160.33520 (10)0.05718 (18)0.68943 (11)0.0270 (3)
H160.38620.02890.75000.032*
N210.71440 (8)0.35624 (14)0.44523 (8)0.0211 (2)
N220.76632 (8)0.30431 (14)0.54929 (9)0.0234 (2)
C230.85436 (9)0.33838 (17)0.54618 (11)0.0252 (3)
C240.86089 (9)0.41270 (18)0.44162 (11)0.0261 (3)
H240.91700.44790.42010.031*
C250.77205 (9)0.42387 (16)0.37845 (10)0.0228 (3)
C260.93179 (10)0.3031 (2)0.64623 (13)0.0374 (4)
H26A0.95510.41040.68280.056*
H26B0.98330.24410.62190.056*
H26C0.90780.23150.69980.056*
C270.73737 (10)0.49322 (19)0.26314 (11)0.0310 (3)
H27A0.78880.55280.23900.046*
H27B0.68550.57260.26360.046*
H27C0.71490.39990.21070.046*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl10.01956 (19)0.0532 (3)0.0377 (2)0.00375 (15)−0.00099 (14)−0.00656 (16)
O10.0241 (5)0.0519 (7)0.0233 (5)−0.0005 (5)0.0006 (4)0.0057 (4)
N10.0177 (6)0.0487 (8)0.0228 (6)−0.0042 (5)0.0009 (5)0.0071 (5)
C10.0182 (6)0.0276 (7)0.0228 (6)−0.0011 (5)0.0033 (5)0.0014 (5)
C20.0181 (6)0.0255 (7)0.0227 (6)−0.0010 (5)0.0029 (5)0.0007 (5)
C30.0197 (6)0.0242 (7)0.0209 (6)0.0003 (5)0.0030 (5)−0.0023 (5)
C110.0203 (6)0.0229 (6)0.0243 (6)−0.0023 (5)0.0056 (5)−0.0041 (5)
C120.0211 (6)0.0259 (7)0.0229 (6)−0.0003 (5)0.0055 (5)−0.0026 (5)
C130.0194 (6)0.0290 (7)0.0292 (6)0.0005 (5)0.0038 (5)−0.0078 (5)
C140.0234 (7)0.0352 (8)0.0401 (8)−0.0051 (6)0.0135 (6)−0.0043 (6)
C150.0331 (8)0.0337 (8)0.0328 (7)−0.0028 (6)0.0145 (6)0.0030 (6)
C160.0274 (7)0.0286 (7)0.0250 (6)−0.0010 (6)0.0058 (5)0.0015 (5)
N210.0197 (5)0.0255 (6)0.0183 (5)−0.0011 (4)0.0044 (4)0.0000 (4)
N220.0195 (5)0.0299 (6)0.0199 (5)0.0003 (5)0.0021 (4)0.0019 (4)
C230.0193 (6)0.0296 (7)0.0263 (6)0.0005 (5)0.0042 (5)−0.0025 (5)
C240.0222 (6)0.0303 (7)0.0279 (7)−0.0047 (6)0.0102 (5)−0.0028 (5)
C250.0261 (6)0.0215 (6)0.0231 (6)−0.0031 (5)0.0104 (5)−0.0032 (5)
C260.0199 (7)0.0555 (10)0.0345 (8)0.0007 (7)0.0012 (6)0.0059 (7)
C270.0347 (7)0.0370 (8)0.0226 (6)−0.0034 (6)0.0090 (6)0.0028 (6)

Geometric parameters (Å, °)

Cl1—C131.7461 (14)C14—H140.9500
O1—C31.2116 (16)C15—C161.3767 (19)
N1—C111.3762 (17)C15—H150.9500
N1—C11.4466 (16)C16—H160.9500
N1—H10.828 (18)N21—N221.3850 (15)
C1—C21.5165 (17)N21—C251.3925 (16)
C1—H1A0.9900N22—C231.3164 (17)
C1—H1B0.9900C23—C241.4197 (18)
C2—C31.5085 (17)C23—C261.4916 (19)
C2—H2A0.9900C24—C251.3540 (19)
C2—H2B0.9900C24—H240.9500
C3—N211.3964 (17)C25—C271.4850 (18)
C11—C121.3950 (18)C26—H26A0.9800
C11—C161.4093 (18)C26—H26B0.9800
C12—C131.3909 (19)C26—H26C0.9800
C12—H120.9500C27—H27A0.9800
C13—C141.381 (2)C27—H27B0.9800
C14—C151.392 (2)C27—H27C0.9800
C11—N1—C1123.43 (12)C16—C15—H15119.4
C11—N1—H1115.4 (12)C14—C15—H15119.4
C1—N1—H1119.0 (12)C15—C16—C11120.61 (13)
N1—C1—C2107.73 (10)C15—C16—H16119.7
N1—C1—H1A110.2C11—C16—H16119.7
C2—C1—H1A110.2N22—N21—C25111.49 (10)
N1—C1—H1B110.2N22—N21—C3118.72 (10)
C2—C1—H1B110.2C25—N21—C3129.78 (11)
H1A—C1—H1B108.5C23—N22—N21104.72 (10)
C3—C2—C1113.30 (10)N22—C23—C24111.36 (11)
C3—C2—H2A108.9N22—C23—C26120.32 (12)
C1—C2—H2A108.9C24—C23—C26128.29 (12)
C3—C2—H2B108.9C25—C24—C23106.98 (11)
C1—C2—H2B108.9C25—C24—H24126.5
H2A—C2—H2B107.7C23—C24—H24126.5
O1—C3—N21121.39 (11)C24—C25—N21105.44 (11)
O1—C3—C2124.12 (12)C24—C25—C27130.10 (12)
N21—C3—C2114.49 (10)N21—C25—C27124.45 (12)
N1—C11—C12122.53 (12)C23—C26—H26A109.5
N1—C11—C16118.64 (12)C23—C26—H26B109.5
C12—C11—C16118.81 (12)H26A—C26—H26B109.5
C13—C12—C11118.80 (12)C23—C26—H26C109.5
C13—C12—H12120.6H26A—C26—H26C109.5
C11—C12—H12120.6H26B—C26—H26C109.5
C14—C13—C12122.99 (13)C25—C27—H27A109.5
C14—C13—Cl1118.68 (11)C25—C27—H27B109.5
C12—C13—Cl1118.33 (11)H27A—C27—H27B109.5
C13—C14—C15117.55 (13)C25—C27—H27C109.5
C13—C14—H14121.2H27A—C27—H27C109.5
C15—C14—H14121.2H27B—C27—H27C109.5
C16—C15—C14121.21 (13)
C11—N1—C1—C2−178.65 (12)O1—C3—N21—N22−177.55 (12)
N1—C1—C2—C3178.34 (11)C2—C3—N21—N221.99 (16)
C1—C2—C3—O1−6.68 (19)O1—C3—N21—C251.0 (2)
C1—C2—C3—N21173.80 (11)C2—C3—N21—C25−179.47 (12)
C1—N1—C11—C120.5 (2)C25—N21—N22—C23−0.40 (14)
C1—N1—C11—C16178.65 (13)C3—N21—N22—C23178.39 (11)
N1—C11—C12—C13176.66 (12)N21—N22—C23—C240.26 (15)
C16—C11—C12—C13−1.49 (19)N21—N22—C23—C26178.52 (12)
C11—C12—C13—C140.5 (2)N22—C23—C24—C25−0.02 (16)
C11—C12—C13—Cl1−179.22 (10)C26—C23—C24—C25−178.12 (14)
C12—C13—C14—C150.7 (2)C23—C24—C25—N21−0.22 (14)
Cl1—C13—C14—C15−179.52 (11)C23—C24—C25—C27179.06 (13)
C13—C14—C15—C16−1.0 (2)N22—N21—C25—C240.39 (14)
C14—C15—C16—C110.0 (2)C3—N21—C25—C24−178.23 (12)
N1—C11—C16—C15−176.98 (13)N22—N21—C25—C27−178.94 (12)
C12—C11—C16—C151.2 (2)C3—N21—C25—C272.4 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.828 (18)2.293 (19)3.1101 (15)169.1 (16)

Symmetry codes: (i) x, −y+1/2, z+1/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HK2680).

References

  • Akarca, U. S. (2005). Curr. Pharm. Des.11, 1779–1784. [PubMed]
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  • Stoe & Cie (2001). X-AREA and X-RED Stoe & Cie, Darmstadt, Germany.

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