PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of actaeInternational Union of Crystallographysearchopen accessarticle submissionjournal home pagethis article
 
Acta Crystallogr Sect E Struct Rep Online. 2010 November 1; 66(Pt 11): o2815–o2816.
Published online 2010 October 20. doi:  10.1107/S1600536810040596
PMCID: PMC3009262

1-(4-Fluoro­phen­yl)-3-methyl-4-phenyl­sulfanyl-1H-pyrazol-5(4H)-one

Abstract

The title compound, C16H13FN2OS, has undergone enol-to-keto tautomerism during the crystallization process. The 1H-pyrazole-5-one ring [maximum deviation = 0.0198 (11) Å] is inclined at angles of 33.10 (5) and 79.57 (5)° with respect to the fluoro­phenyl [maximum deviation = 0.0090 (12) Å] and phenyl­thiol [maximum deviation = 0.0229 (3) Å] rings attached to it. In the crystal, neighbouring mol­ecules are linked into inversion dimers, generating R 2 2(8) ring motifs. These dimers are further linked into two-dimensional arrays parallel to the bc plane via inter­molecular N—H(...)O, C—H(...)F and C—H(...)O hydrogen bonds. The crystal is further stabilized by weak π–π [centroid–centroid distance = 3.6921 (7) Å] and C—H(...)π inter­actions.

Related literature

For pyrazole derivatives and their microbial activity, see: Ragavan et al. (2009 [triangle], 2010 [triangle]). For related structures, see: Shahani et al. (2009 [triangle], 2010a [triangle],b [triangle],c [triangle]). For hydrogen-bond motifs, see: Bernstein et al. (1995 [triangle]). For bond-length data, see: Allen et al. (1987 [triangle]). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o2815-scheme1.jpg

Experimental

Crystal data

  • C16H13FN2OS
  • M r = 300.34
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o2815-efi1.jpg
  • a = 17.2628 (3) Å
  • b = 7.28340 (1) Å
  • c = 11.4877 (2) Å
  • β = 91.138 (1)°
  • V = 1444.09 (4) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.24 mm−1
  • T = 100 K
  • 0.37 × 0.17 × 0.14 mm

Data collection

  • Bruker SMART APEXII CCD diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2009 [triangle]) T min = 0.918, T max = 0.968
  • 21517 measured reflections
  • 5704 independent reflections
  • 4543 reflections with I > 2σ(I)
  • R int = 0.037

Refinement

  • R[F 2 > 2σ(F 2)] = 0.043
  • wR(F 2) = 0.113
  • S = 1.03
  • 5704 reflections
  • 195 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.48 e Å−3
  • Δρmin = −0.28 e Å−3

Data collection: APEX2 (Bruker, 2009 [triangle]); cell refinement: SAINT (Bruker, 2009 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810040596/hb5673sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810040596/hb5673Isup2.hkl

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

Acknowledgments

HKF and TSH thank Universiti Sains Malaysia (USM) for the Research University Grant (1001/PFIZIK/811160). TSH also thanks USM for the award of a research fellowship. VV is grateful to the DST-India for funding through the Young Scientist Scheme (Fast Track Proposal).

supplementary crystallographic information

Comment

Antibacterial and antifungal activities of the azoles are most widely studied and some of them are in clinical practice as anti-microbial agents. However, the azole-resistant strain had led to the development of new antimicrobial compounds. In particular pyrazole derivatives are extensively studied and used as antimicrobial agents. Pyrazole is an important class of heterocyclic compounds and many pyrazole derivatives are reported to have the broad spectrum of biological properties, such as anti-inflammatory, antifungal, herbicidal, anti-tumour, cytotoxic, molecular modelling, and antiviral activities. Pyrazole derivatives also act as antiangiogenic agents, A3 adenosine receptor antagonists, neuropeptide YY5 receptor antagonists, kinase inhibitor for treatment of type 2 diabetes, hyperlipidemia, obesity, and thrombopiotinmimetics. Recently urea derivatives of pyrazoles have been reported as potent inhibitors of p38 kinase. Since the high electronegativity of halogens (particularly chlorine and fluorine) in the aromatic part of the drug molecules play an important role in enhancing their biological activity, we are interested to have 4-fluoro or 4-chloro substitution in the aryls of 1,5-diaryl pyrazoles. As part of our on-going research aiming the synthesis of new antimicrobial compounds, we have reported the synthesis of novel pyrazole derivatives and their microbial activities (Ragavan et al., 2009; 2010). The structure of the title compound is presented here. The synthesis lead to the enol form of the compound (see Ragavan et al., 2009). However the single crystal structure determination gives the keto form. Therefore the compound undergoes an enol-to-keto tautomerism during crystallization. The interconversion of the two forms involves the movement of a proton and the shifting of bonding electrons; hence, the isomerism qualifies as tautomerism (Fig. 2)

The asymmetric unit of the title compound, (Fig. 1), consists of three rings, namely fluorophenyl (F1/C1–C6), 5-3methyl-2,5dihydro-1H-pyrazol-3-one (N1/N2/C7–C9/O1/C16) and phenylthiol (S1/C10–C15).The 1-(4-fluorophenyl)-3-methyl-4-(phenylthio)-1H-pyrazol-5-ol undergoes an enol-to-ketotautomerism during the crystallization process (Fig. 2). The 1H-pyrazole-5-one ring (maximum deviation 0.0198 (11) Å at atom C8) is inclined at angles of 33.10 (5) and 79.57 (5)° with respect to the fluorophenyl (maximum deviation 0.0090 (12) at atom C2) and phenylthiol (maximum deviation 0.0229 (3) at atom S1) rings attached to it. The bond lengths (Allen et al., 1987) and angles are within normal ranges and comparable to the closely related structures (Shahani et al., 2009; 2010a,b).

In the crystal packing (Fig. 3), intermolecular C2—H2A···F1 hydrogen bonds (Table 1) link the neighbouring molecules into dimers, generating R22(8) ring motifs (Bernstein et al., 1995). These dimers are further linked into two-dimensional arrays parallel to the bc plane by intermolecular N2—H1N2···O1, C2—H2A···F1, C4—H4A···F1 and C5—H5A···O1 hydrogen bonds (Table 1). Weak π–π interactions were observed [Cg2···Cg2 = 3.6921 (7) Å, symmetry code = –X, –Y, 1-Z], Cg2 is the centroid of the benzene ring (C1–C6). The crystal structure is further stabilized by C—H···π interactions (Table 1), involving the C10–C15 (centroid Cg 1) and N1/N2/C7/C8/C9 rings (centroid Cg3).

Experimental

The compound has been synthesized using the method available in the literature (Ragavan et al., 2009) and recrystallized using an ethanol-chloroform 1:1 mixture to generate colourless needles of (I). Yield: 58%. M.Pt: 475 K.

Refinement

The hydrogen atoms bound to C atoms were positioned geometrically [C–H = 0.9300 to 0.9600 Å] with Uiso(H) =1.2 or 1.5Uiso(C). The hydrogen atom attached to the N2 atom was located from the difference map and refined freely.

Figures

Fig. 1.
The molecular structure of the title compound, showing 50% probability displacement ellipsoids.
Fig. 2.
Enol-to-keto tautomerism of the title compound during crystallization process.
Fig. 3.
The crystal packing of the title compound, showing two two-dimensional arrays parallel to the bc plane. Intermolecular hydrogen bonds are shown as dashed lines.

Crystal data

C16H13FN2OSF(000) = 624
Mr = 300.34Dx = 1.381 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 5911 reflections
a = 17.2628 (3) Åθ = 2.4–33.6°
b = 7.28340 (1) ŵ = 0.24 mm1
c = 11.4877 (2) ÅT = 100 K
β = 91.138 (1)°Needle, colourless
V = 1444.09 (4) Å30.37 × 0.17 × 0.14 mm
Z = 4

Data collection

Bruker SMART APEXII CCD diffractometer5704 independent reflections
Radiation source: fine-focus sealed tube4543 reflections with I > 2σ(I)
graphiteRint = 0.037
[var phi] and ω scansθmax = 33.6°, θmin = 2.4°
Absorption correction: multi-scan (SADABS; Bruker, 2009)h = −25→26
Tmin = 0.918, Tmax = 0.968k = −9→11
21517 measured reflectionsl = −17→17

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.043Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.113H atoms treated by a mixture of independent and constrained refinement
S = 1.03w = 1/[σ2(Fo2) + (0.0502P)2 + 0.527P] where P = (Fo2 + 2Fc2)/3
5704 reflections(Δ/σ)max < 0.001
195 parametersΔρmax = 0.48 e Å3
0 restraintsΔρmin = −0.28 e Å3

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cyrosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K.
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
S10.287633 (16)0.50655 (4)0.76602 (2)0.01812 (7)
F10.01268 (6)−0.41073 (14)0.38015 (8)0.0433 (3)
O10.17691 (5)0.14246 (12)0.74551 (7)0.02106 (17)
N10.17513 (6)0.18952 (13)0.54527 (8)0.01725 (18)
N20.20721 (6)0.31449 (14)0.46958 (8)0.01727 (18)
C10.13682 (7)−0.12951 (16)0.56378 (10)0.0193 (2)
H1A0.1672−0.13860.63130.023*
C20.09597 (7)−0.28107 (18)0.52250 (11)0.0231 (2)
H2A0.0978−0.39240.56210.028*
C30.05246 (8)−0.2620 (2)0.42099 (11)0.0271 (3)
C40.04640 (7)−0.1000 (2)0.36073 (10)0.0285 (3)
H4A0.0161−0.09240.29300.034*
C50.08635 (7)0.05268 (19)0.40275 (10)0.0226 (2)
H5A0.08260.16460.36410.027*
C60.13208 (6)0.03598 (16)0.50366 (9)0.0166 (2)
C70.24940 (6)0.43573 (15)0.53067 (9)0.01692 (19)
C80.24443 (6)0.39363 (15)0.64842 (9)0.01656 (19)
C90.19702 (6)0.23394 (15)0.65843 (9)0.01662 (19)
C100.36501 (6)0.35655 (15)0.80605 (9)0.01676 (19)
C110.39018 (7)0.21470 (17)0.73533 (10)0.0211 (2)
H11A0.36520.19230.66430.025*
C120.45278 (7)0.10600 (18)0.77057 (11)0.0238 (2)
H12A0.46940.01140.72280.029*
C130.49050 (7)0.13786 (18)0.87642 (11)0.0231 (2)
H13A0.53290.06660.89910.028*
C140.46437 (7)0.27724 (17)0.94827 (10)0.0220 (2)
H14A0.48900.29801.01980.026*
C150.40165 (7)0.38605 (17)0.91402 (10)0.0199 (2)
H15A0.38420.47830.96290.024*
C160.29242 (7)0.58417 (17)0.47078 (10)0.0228 (2)
H16A0.25920.64040.41300.034*
H16B0.33700.53310.43400.034*
H16C0.30880.67480.52670.034*
H1N20.1992 (11)0.314 (3)0.3895 (18)0.049 (6)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S10.02393 (14)0.01636 (13)0.01404 (12)0.00137 (10)−0.00028 (9)−0.00369 (9)
F10.0523 (6)0.0484 (6)0.0292 (4)−0.0311 (5)−0.0029 (4)−0.0083 (4)
O10.0323 (4)0.0221 (4)0.0089 (3)−0.0046 (3)0.0013 (3)0.0002 (3)
N10.0241 (4)0.0185 (4)0.0092 (4)−0.0017 (3)0.0003 (3)0.0006 (3)
N20.0237 (4)0.0192 (4)0.0090 (4)0.0002 (3)0.0013 (3)0.0012 (3)
C10.0193 (5)0.0206 (5)0.0179 (5)0.0009 (4)−0.0019 (4)−0.0015 (4)
C20.0234 (5)0.0226 (5)0.0232 (5)−0.0027 (4)0.0001 (4)−0.0022 (4)
C30.0268 (6)0.0346 (7)0.0200 (5)−0.0133 (5)0.0019 (4)−0.0074 (5)
C40.0260 (6)0.0451 (8)0.0143 (5)−0.0124 (5)−0.0026 (4)0.0009 (5)
C50.0215 (5)0.0331 (6)0.0132 (5)−0.0032 (5)−0.0020 (4)0.0028 (4)
C60.0168 (4)0.0212 (5)0.0118 (4)0.0002 (4)0.0007 (3)−0.0026 (4)
C70.0212 (5)0.0166 (5)0.0130 (4)0.0022 (4)0.0018 (3)0.0002 (4)
C80.0221 (5)0.0163 (5)0.0114 (4)0.0009 (4)0.0009 (3)−0.0011 (4)
C90.0225 (5)0.0182 (5)0.0092 (4)0.0009 (4)−0.0002 (3)−0.0015 (3)
C100.0198 (5)0.0173 (5)0.0131 (4)−0.0018 (4)0.0015 (3)0.0000 (4)
C110.0246 (5)0.0244 (5)0.0144 (5)0.0027 (4)0.0011 (4)−0.0037 (4)
C120.0273 (6)0.0255 (6)0.0189 (5)0.0056 (5)0.0037 (4)−0.0023 (4)
C130.0227 (5)0.0271 (6)0.0196 (5)0.0021 (4)0.0018 (4)0.0051 (4)
C140.0245 (5)0.0257 (6)0.0158 (5)−0.0033 (4)−0.0015 (4)0.0031 (4)
C150.0252 (5)0.0210 (5)0.0134 (4)−0.0027 (4)0.0008 (4)−0.0013 (4)
C160.0295 (6)0.0205 (5)0.0186 (5)−0.0013 (4)0.0052 (4)0.0030 (4)

Geometric parameters (Å, °)

S1—C81.7371 (11)C5—H5A0.9300
S1—C101.7790 (11)C7—C81.3913 (15)
F1—C31.3613 (15)C7—C161.4879 (17)
O1—C91.2567 (13)C8—C91.4280 (16)
N1—N21.3821 (13)C10—C111.3894 (16)
N1—C91.3848 (13)C10—C151.3977 (15)
N1—C61.4203 (14)C11—C121.3933 (17)
N2—C71.3351 (14)C11—H11A0.9300
N2—H1N20.93 (2)C12—C131.3873 (17)
C1—C21.3884 (16)C12—H12A0.9300
C1—C61.3908 (16)C13—C141.3893 (18)
C1—H1A0.9300C13—H13A0.9300
C2—C31.3814 (17)C14—C151.3922 (17)
C2—H2A0.9300C14—H14A0.9300
C3—C41.371 (2)C15—H15A0.9300
C4—C51.3898 (18)C16—H16A0.9600
C4—H4A0.9300C16—H16B0.9600
C5—C61.3948 (15)C16—H16C0.9600
C8—S1—C10102.64 (5)C7—C8—S1128.16 (9)
N2—N1—C9109.36 (9)C9—C8—S1124.12 (8)
N2—N1—C6121.35 (8)O1—C9—N1123.29 (10)
C9—N1—C6129.13 (9)O1—C9—C8131.59 (10)
C7—N2—N1109.03 (9)N1—C9—C8105.12 (9)
C7—N2—H1N2126.2 (13)C11—C10—C15119.47 (11)
N1—N2—H1N2124.7 (13)C11—C10—S1123.19 (8)
C2—C1—C6119.67 (10)C15—C10—S1117.34 (9)
C2—C1—H1A120.2C10—C11—C12120.16 (10)
C6—C1—H1A120.2C10—C11—H11A119.9
C3—C2—C1118.17 (12)C12—C11—H11A119.9
C3—C2—H2A120.9C13—C12—C11120.50 (11)
C1—C2—H2A120.9C13—C12—H12A119.8
F1—C3—C4118.56 (11)C11—C12—H12A119.8
F1—C3—C2118.22 (13)C12—C13—C14119.39 (11)
C4—C3—C2123.22 (12)C12—C13—H13A120.3
C3—C4—C5118.73 (11)C14—C13—H13A120.3
C3—C4—H4A120.6C13—C14—C15120.52 (10)
C5—C4—H4A120.6C13—C14—H14A119.7
C4—C5—C6119.19 (12)C15—C14—H14A119.7
C4—C5—H5A120.4C14—C15—C10119.94 (11)
C6—C5—H5A120.4C14—C15—H15A120.0
C1—C6—C5121.00 (11)C10—C15—H15A120.0
C1—C6—N1119.34 (9)C7—C16—H16A109.5
C5—C6—N1119.66 (11)C7—C16—H16B109.5
N2—C7—C8108.77 (10)H16A—C16—H16B109.5
N2—C7—C16120.64 (10)C7—C16—H16C109.5
C8—C7—C16130.59 (10)H16A—C16—H16C109.5
C7—C8—C9107.72 (9)H16B—C16—H16C109.5
C9—N1—N2—C70.64 (12)C16—C7—C8—S10.70 (19)
C6—N1—N2—C7−175.10 (10)C10—S1—C8—C7−104.41 (11)
C6—C1—C2—C30.90 (18)C10—S1—C8—C974.55 (10)
C1—C2—C3—F1179.69 (12)N2—N1—C9—O1−179.24 (10)
C1—C2—C3—C4−1.5 (2)C6—N1—C9—O1−3.94 (18)
F1—C3—C4—C5179.41 (12)N2—N1—C9—C80.04 (12)
C2—C3—C4—C50.6 (2)C6—N1—C9—C8175.35 (11)
C3—C4—C5—C60.9 (2)C7—C8—C9—O1178.53 (12)
C2—C1—C6—C50.50 (18)S1—C8—C9—O1−0.61 (19)
C2—C1—C6—N1−178.88 (11)C7—C8—C9—N1−0.68 (12)
C4—C5—C6—C1−1.40 (18)S1—C8—C9—N1−179.82 (8)
C4—C5—C6—N1177.98 (11)C8—S1—C10—C1114.04 (11)
N2—N1—C6—C1144.74 (11)C8—S1—C10—C15−166.31 (9)
C9—N1—C6—C1−30.08 (17)C15—C10—C11—C12−1.69 (18)
N2—N1—C6—C5−34.65 (16)S1—C10—C11—C12177.96 (10)
C9—N1—C6—C5150.54 (12)C10—C11—C12—C130.10 (19)
N1—N2—C7—C8−1.07 (12)C11—C12—C13—C141.21 (19)
N1—N2—C7—C16178.48 (10)C12—C13—C14—C15−0.93 (19)
N2—C7—C8—C91.09 (13)C13—C14—C15—C10−0.66 (18)
C16—C7—C8—C9−178.40 (11)C11—C10—C15—C141.97 (17)
N2—C7—C8—S1−179.82 (9)S1—C10—C15—C14−177.70 (9)

Hydrogen-bond geometry (Å, °)

Cg1 and Cg3 are the centroids of the pyrazol (N1/N2/C7–C9) and benzene ring (C10–C15) rings, respectively.
D—H···AD—HH···AD···AD—H···A
N2—H1N2···O1i0.93 (2)1.72 (2)2.6352 (12)168 (2)
C2—H2A···F1ii0.932.493.1450 (16)128
C4—H4A···F1iii0.932.433.2381 (15)145
C5—H5A···O1i0.932.563.2786 (15)134
C2—H2A···Cg1iv0.932.943.6300 (14)132
C12—H12A···Cg3v0.932.743.5928 (14)153
C16—H16B···Cg3vi0.962.793.6826 (13)155

Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) −x, −y−1, −z+1; (iii) −x, y+1/2, −z+1/2; (iv) x, y−1, z; (v) −x+1, y−1/2, −z+3/2; (vi) x, −y−1/2, z−3/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HB5673).

References

  • Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19.
  • Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl.34, 1555–1573.
  • Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wiscosin, USA.
  • Cosier, J. & Glazer, A. M. (1986). J. Appl. Cryst.19, 105–107.
  • Ragavan, R. V., Vijayakumar, V. & Kumari, N. S. (2009). Eur. J. Med. Chem.44, 3852–3857. [PubMed]
  • Ragavan, R. V., Vijayakumar, V. & Kumari, N. S. (2010). Eur. J. Med. Chem.45, 1173–1180. [PubMed]
  • Shahani, T., Fun, H.-K., Ragavan, R. V., Vijayakumar, V. & Sarveswari, S. (2009). Acta Cryst. E65, o3249–o3250. [PMC free article] [PubMed]
  • Shahani, T., Fun, H.-K., Ragavan, R. V., Vijayakumar, V. & Sarveswari, S. (2010a). Acta Cryst. E66, o142–o143. [PMC free article] [PubMed]
  • Shahani, T., Fun, H.-K., Ragavan, R. V., Vijayakumar, V. & Sarveswari, S. (2010b). Acta Cryst. E66, o1357–o1358. [PMC free article] [PubMed]
  • Shahani, T., Fun, H.-K., Ragavan, R. V., Vijayakumar, V. & Sarveswari, S. (2010c). Acta Cryst. E66, o1482–o1483. [PMC free article] [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography