PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of actaeInternational Union of Crystallographysearchopen accessarticle submissionjournal home pagethis article
 
Acta Crystallogr Sect E Struct Rep Online. 2008 October 1; 64(Pt 10): o1924.
Published online 2008 September 13. doi:  10.1107/S1600536808028559
PMCID: PMC2959372

5-Methyl-2-phenyl-2H-pyrazol-3-ol

Abstract

The title compound, C10H10N2O, known as Edaravone (MCI-186), was crystallized from methanol. The two independent mol­ecules in the asymmetric unit are linked through an O—H(...)O hydrogen bond. One mol­ecule adopts a ketone form, while the other adopts an enol form. In the crystal structure, mol­ecules are linked through inter­molecular N—H(...)O hydrogen bonds, forming chains running along the b axis.

Related literature

For background to the compound, see: Watanabe et al. (1994 [triangle]); The Edaravone Acute Infarction Study Group (2003 [triangle]). For bond-length data, see: Allen et al. (1987 [triangle]). [triangle]

An external file that holds a picture, illustration, etc.
Object name is e-64-o1924-scheme1.jpg

Experimental

Crystal data

  • C10H10N2O
  • M r = 174.20
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-o1924-efi1.jpg
  • a = 10.336 (2) Å
  • b = 11.154 (2) Å
  • c = 15.863 (3) Å
  • β = 95.157 (3)°
  • V = 1821.4 (6) Å3
  • Z = 8
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 298 (2) K
  • 0.23 × 0.23 × 0.20 mm

Data collection

  • Bruker SMART CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 1996 [triangle]) T min = 0.981, T max = 0.983
  • 10551 measured reflections
  • 3923 independent reflections
  • 2894 reflections with I > 2σ(I)
  • R int = 0.025

Refinement

  • R[F 2 > 2σ(F 2)] = 0.040
  • wR(F 2) = 0.106
  • S = 1.04
  • 3923 reflections
  • 243 parameters
  • 2 restraints
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.17 e Å−3
  • Δρmin = −0.14 e Å−3

Data collection: SMART (Bruker, 2002 [triangle]); cell refinement: SAINT (Bruker, 2002 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808028559/sg2259sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808028559/sg2259Isup2.hkl

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

supplementary crystallographic information

Comment

Edaravone (5-methyl-2-phenyl-2H-pyrazol-3-ol, MCI-186) is a free-radical scavenger that was approved by the Ministry of Health, Labor, and Welfare of Japan in 2001, and is now widely used for the treatment of acute cerebral infarction (Watanabe et al.., 1994; The Edaravone Acute Infarction Study Group, 2003). We report in this paper the crystal structure of the compound, (I).

The compound consists of two independent molecules (Fig. 1), which are linked through an intramolecular O2—H2B···O1 hydrogen bond (Table 1). One molecule adopts a ketone form, while the other adopts an enol form. In the ketone molecule, the dihedral angle between the C1–C6 benzene ring and the N1/N2/C9/C8/C7 ring is 22.9 (2)°. In the enol molecule, the dihedral angle between the C11–C16 benzene ring and the N3/N4/C19/C18/C17 ring is 34.3 (2)°. In the compound, all the bond lengths are within normal ranges (Allen et al., 1987). The bond length of C17—O2 [1.325 (2) Å] is longer than that of C7—O1 [1.260 (2) Å], which is caused by the enol form.

In the crystal structure, molecules are linked through intermolecular N–H···O hydrogen bonds (Table 1), forming chains running along the b axis (Fig. 2).

Experimental

The crystal of the compound was recrystallized by edaravone in methanol.

Refinement

H2A and H2B were located in a difference Fourier map and refined isotropically, with N–H and O–H distances restrained to 0.90 (1) and 0.85 (1) Å, and with Uiso(H) set to 0.08 Å2. Other H atoms were constrained to idealized geometries, with C–H = 0.93–0.96 Å, and with Uiso(H) set to 1.2Ueq(C) and 1.5Ueq(methyl C).

Figures

Fig. 1.
The structure of (I) at the 30% probability level. Intramolecular hydrogen bonds are shown as dashed lines.
Fig. 2.
Molecular packing of (I), viewed along the a axis. Intermolecular hydrogen bonds are shown as dashed lines.

Crystal data

C10H10N2OF(000) = 736
Mr = 174.20Dx = 1.271 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 3931 reflections
a = 10.336 (2) Åθ = 2.3–29.0°
b = 11.154 (2) ŵ = 0.09 mm1
c = 15.863 (3) ÅT = 298 K
β = 95.157 (3)°Block, colorless
V = 1821.4 (6) Å30.23 × 0.23 × 0.20 mm
Z = 8

Data collection

Bruker SMART CCD area-detector diffractometer3923 independent reflections
Radiation source: fine-focus sealed tube2894 reflections with I > 2σ(I)
graphiteRint = 0.025
ω scanθmax = 27.0°, θmin = 2.2°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)h = −13→11
Tmin = 0.981, Tmax = 0.983k = −13→14
10551 measured reflectionsl = −20→18

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.040H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.106w = 1/[σ2(Fo2) + (0.0428P)2 + 0.3053P] where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max < 0.001
3923 reflectionsΔρmax = 0.17 e Å3
243 parametersΔρmin = −0.14 e Å3
2 restraintsExtinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0087 (12)

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
O10.76081 (11)0.23408 (9)0.09473 (8)0.0652 (3)
O20.63865 (11)0.42520 (9)0.07652 (7)0.0577 (3)
N10.80235 (11)0.03414 (9)0.07061 (8)0.0469 (3)
N20.76341 (13)−0.04917 (10)0.00921 (8)0.0516 (3)
N30.69321 (11)0.62596 (9)0.06745 (7)0.0418 (3)
N40.76998 (12)0.70070 (10)0.02382 (8)0.0490 (3)
C10.91015 (13)0.01075 (12)0.12978 (9)0.0457 (3)
C20.92942 (16)0.07840 (15)0.20276 (10)0.0603 (4)
H20.87220.13990.21310.072*
C31.03427 (19)0.05375 (19)0.26009 (12)0.0768 (5)
H31.04810.09970.30900.092*
C41.1181 (2)−0.0372 (2)0.24600 (13)0.0814 (6)
H41.1881−0.05360.28530.098*
C51.09872 (17)−0.10395 (18)0.17403 (14)0.0755 (5)
H51.1557−0.16610.16470.091*
C60.99550 (15)−0.08041 (15)0.11475 (11)0.0597 (4)
H60.9837−0.12550.06530.072*
C70.73814 (14)0.14046 (12)0.05144 (10)0.0486 (4)
C80.65398 (16)0.11675 (14)−0.02083 (10)0.0566 (4)
H80.59700.1713−0.04860.068*
C90.66976 (15)0.00076 (14)−0.04331 (10)0.0536 (4)
C100.6047 (2)−0.07170 (17)−0.11335 (11)0.0760 (5)
H10A0.6586−0.0744−0.15960.114*
H10B0.5227−0.0359−0.13210.114*
H10C0.5908−0.1517−0.09370.114*
C110.61818 (14)0.67394 (12)0.12999 (8)0.0441 (3)
C120.49765 (15)0.62664 (14)0.14196 (10)0.0545 (4)
H120.46550.56110.11040.065*
C130.42556 (18)0.67832 (19)0.20167 (12)0.0755 (6)
H130.34500.64620.21080.091*
C140.4708 (2)0.7760 (2)0.24752 (12)0.0860 (7)
H140.42050.81100.28660.103*
C150.5904 (2)0.82150 (17)0.23553 (11)0.0799 (6)
H150.62130.88760.26690.096*
C160.66614 (18)0.77067 (13)0.17737 (10)0.0584 (4)
H160.74820.80120.17030.070*
C170.70530 (13)0.51085 (11)0.04194 (9)0.0430 (3)
C180.79096 (15)0.51055 (13)−0.01882 (10)0.0526 (4)
H180.81900.4445−0.04790.063*
C190.82756 (15)0.62954 (13)−0.02813 (10)0.0510 (4)
C200.91583 (19)0.68181 (17)−0.08846 (13)0.0794 (6)
H20A0.90600.7674−0.09000.119*
H20B0.89380.6496−0.14400.119*
H20C1.00420.6619−0.07000.119*
H2A0.7692 (17)−0.1287 (9)0.0208 (11)0.080*
H2B0.6823 (16)0.3585 (12)0.0773 (12)0.080*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0757 (7)0.0322 (5)0.0864 (8)0.0043 (5)−0.0001 (6)−0.0043 (5)
O20.0673 (7)0.0311 (5)0.0772 (7)0.0007 (5)0.0205 (6)0.0059 (5)
N10.0531 (7)0.0283 (6)0.0577 (7)0.0011 (5)−0.0031 (6)0.0011 (5)
N20.0640 (8)0.0310 (6)0.0581 (7)0.0018 (5)−0.0030 (6)0.0012 (5)
N30.0493 (6)0.0298 (6)0.0476 (6)0.0024 (5)0.0114 (5)0.0017 (5)
N40.0588 (8)0.0324 (6)0.0582 (7)−0.0021 (5)0.0185 (6)0.0015 (5)
C10.0456 (8)0.0362 (7)0.0551 (8)−0.0040 (6)0.0031 (6)0.0098 (6)
C20.0646 (10)0.0555 (10)0.0603 (10)−0.0023 (8)0.0035 (8)0.0003 (8)
C30.0793 (13)0.0876 (14)0.0607 (11)−0.0113 (11)−0.0084 (9)0.0024 (10)
C40.0653 (12)0.1020 (16)0.0736 (12)−0.0004 (11)−0.0122 (10)0.0206 (12)
C50.0569 (10)0.0769 (12)0.0919 (14)0.0161 (9)0.0016 (10)0.0187 (11)
C60.0567 (9)0.0531 (9)0.0687 (10)0.0082 (7)0.0024 (8)0.0050 (8)
C70.0513 (8)0.0310 (7)0.0640 (9)0.0023 (6)0.0082 (7)0.0075 (7)
C80.0597 (9)0.0453 (9)0.0635 (10)0.0101 (7)−0.0019 (8)0.0127 (7)
C90.0599 (9)0.0477 (9)0.0523 (8)0.0013 (7)−0.0006 (7)0.0069 (7)
C100.0886 (13)0.0739 (12)0.0622 (10)−0.0045 (10)−0.0120 (9)−0.0032 (9)
C110.0544 (8)0.0339 (7)0.0447 (7)0.0122 (6)0.0093 (6)0.0067 (6)
C120.0524 (9)0.0531 (9)0.0586 (9)0.0130 (7)0.0090 (7)0.0135 (7)
C130.0686 (11)0.0872 (14)0.0749 (12)0.0326 (10)0.0304 (9)0.0286 (11)
C140.1171 (18)0.0853 (15)0.0612 (11)0.0533 (13)0.0383 (12)0.0143 (11)
C150.1298 (18)0.0540 (11)0.0579 (10)0.0258 (11)0.0198 (11)−0.0063 (8)
C160.0812 (11)0.0414 (8)0.0537 (9)0.0066 (8)0.0121 (8)−0.0019 (7)
C170.0495 (8)0.0285 (6)0.0511 (7)0.0027 (6)0.0048 (6)0.0015 (6)
C180.0622 (9)0.0379 (8)0.0597 (9)0.0065 (7)0.0166 (7)−0.0068 (7)
C190.0538 (8)0.0432 (8)0.0580 (9)0.0022 (6)0.0163 (7)−0.0002 (7)
C200.0868 (13)0.0683 (12)0.0901 (13)−0.0032 (10)0.0467 (11)0.0008 (10)

Geometric parameters (Å, °)

O1—C71.260 (2)C8—C91.356 (2)
O2—C171.325 (2)C8—H80.9300
O2—H2B0.870 (9)C9—C101.485 (2)
N1—C71.379 (2)C10—H10A0.9600
N1—N21.380 (2)C10—H10B0.9600
N1—C11.415 (2)C10—H10C0.9600
N2—C91.340 (2)C11—C161.381 (2)
N2—H2A0.907 (9)C11—C121.382 (2)
N3—C171.355 (2)C12—C131.383 (2)
N3—N41.379 (2)C12—H120.9300
N3—C111.418 (2)C13—C141.369 (3)
N4—C191.323 (2)C13—H130.9300
C1—C61.381 (2)C14—C151.365 (3)
C1—C21.381 (2)C14—H140.9300
C2—C31.378 (2)C15—C161.384 (2)
C2—H20.9300C15—H150.9300
C3—C41.366 (3)C16—H160.9300
C3—H30.9300C17—C181.366 (2)
C4—C51.362 (3)C18—C191.392 (2)
C4—H40.9300C18—H180.9300
C5—C61.383 (2)C19—C201.498 (2)
C5—H50.9300C20—H20A0.9600
C6—H60.9300C20—H20B0.9600
C7—C81.400 (2)C20—H20C0.9600
C17—O2—H2B109.5 (13)C9—C10—H10B109.5
C7—N1—N2108.62 (11)H10A—C10—H10B109.5
C7—N1—C1129.74 (12)C9—C10—H10C109.5
N2—N1—C1120.42 (11)H10A—C10—H10C109.5
C9—N2—N1107.91 (11)H10B—C10—H10C109.5
C9—N2—H2A124.3 (11)C16—C11—C12120.50 (14)
N1—N2—H2A120.4 (12)C16—C11—N3118.91 (13)
C17—N3—N4110.49 (11)C12—C11—N3120.57 (13)
C17—N3—C11129.60 (11)C11—C12—C13118.88 (17)
N4—N3—C11119.90 (10)C11—C12—H12120.6
C19—N4—N3105.14 (11)C13—C12—H12120.6
C6—C1—C2120.05 (14)C14—C13—C12121.09 (19)
C6—C1—N1119.90 (13)C14—C13—H13119.5
C2—C1—N1120.05 (13)C12—C13—H13119.5
C3—C2—C1119.32 (17)C15—C14—C13119.52 (17)
C3—C2—H2120.3C15—C14—H14120.2
C1—C2—H2120.3C13—C14—H14120.2
C4—C3—C2120.86 (18)C14—C15—C16120.93 (19)
C4—C3—H3119.6C14—C15—H15119.5
C2—C3—H3119.6C16—C15—H15119.5
C5—C4—C3119.69 (17)C11—C16—C15119.06 (18)
C5—C4—H4120.2C11—C16—H16120.5
C3—C4—H4120.2C15—C16—H16120.5
C4—C5—C6120.84 (18)O2—C17—N3119.60 (12)
C4—C5—H5119.6O2—C17—C18133.19 (13)
C6—C5—H5119.6N3—C17—C18107.21 (12)
C1—C6—C5119.23 (17)C17—C18—C19105.80 (12)
C1—C6—H6120.4C17—C18—H18127.1
C5—C6—H6120.4C19—C18—H18127.1
O1—C7—N1122.01 (13)N4—C19—C18111.36 (13)
O1—C7—C8132.37 (13)N4—C19—C20119.87 (13)
N1—C7—C8105.62 (12)C18—C19—C20128.74 (14)
C9—C8—C7108.35 (13)C19—C20—H20A109.5
C9—C8—H8125.8C19—C20—H20B109.5
C7—C8—H8125.8H20A—C20—H20B109.5
N2—C9—C8109.29 (14)C19—C20—H20C109.5
N2—C9—C10119.47 (14)H20A—C20—H20C109.5
C8—C9—C10131.23 (15)H20B—C20—H20C109.5
C9—C10—H10A109.5

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N2—H2A···N4i0.91 (1)1.90 (1)2.7999 (17)169.(2)
O2—H2B···O10.87 (1)1.62 (1)2.4813 (15)171.(2)

Symmetry codes: (i) x, y−1, z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: SG2259).

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.
  • Bruker (2002). SAINT and SMART Bruker AXS Inc., Madison, Wisconsin, USA.
  • Sheldrick, G. M. (1996). SADABS University of Göttingen, Germany.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • The Edaravone Acute Infarction Study Group (2003). Cerebrovasc. Dis.15, 222–229. [PubMed]
  • Watanabe, T., Yuki, S., Egawa, M. & Nishi, H. (1994). J. Pharmacol. Exp. Ther.268, 1597–1604. [PubMed]

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