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Acta Crystallogr Sect E Struct Rep Online. 2009 December 1; 65(Pt 12): o3249–o3250.
Published online 2009 November 28. doi:  10.1107/S1600536809050302
PMCID: PMC2971925

5-Methoxy­methyl-4-phen­oxy-1H-pyrazol-3-ol

Abstract

In the title compound, C11H12N2O3, the pyrazole ring system is essentially planar [maximum deviation = 0.002 (2) Å] and forms a dihedral angle of 66.93 (9)° with the benzene ring. In the crystal packing, pairs of inter­molecular N—H(...)O and O—H(...)N hydrogen bonds connect neighbouring mol­ecules into dimers, generating R 2 2(10) and R 2 2(8) ring motifs, respectively. The crystal structure is further stabilized by C—H(...)π inter­actions.

Related literature

For the biological activity of pyrazoles, see: Genin et al. (2000 [triangle]); Hsu et al. (1956 [triangle]); Jung et al. (2002 [triangle]); Kudo et al. (1999 [triangle]); Singh et al. (1978 [triangle]); Skipper et al. (1955 [triangle]); Storer et al. (1999 [triangle]); Tewari & Mishra (2001 [triangle]). For pyrazole derivatives, see: Baraldi et al. (2003 [triangle]); Brown et al. (2004 [triangle]); Duma et al. (2000 [triangle]); Heerding (2003 [triangle]); Qiao et al. (2003 [triangle]); Stamford & Wu (2004 [triangle]). For a related structure, see: Goh et al. (2009 [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 for the data collection, see: Cosier & Glazer (1986 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o3249-scheme1.jpg

Experimental

Crystal data

  • C11H12N2O3
  • M r = 220.23
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o3249-efi1.jpg
  • a = 8.8876 (5) Å
  • b = 10.3031 (5) Å
  • c = 12.0083 (6) Å
  • β = 100.917 (3)°
  • V = 1079.7 (1) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.10 mm−1
  • T = 100 K
  • 0.69 × 0.57 × 0.18 mm

Data collection

  • Bruker SMART APEXII CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2005 [triangle]) T min = 0.934, T max = 0.983
  • 14470 measured reflections
  • 3433 independent reflections
  • 2373 reflections with I > 2σ(I)
  • R int = 0.032

Refinement

  • R[F 2 > 2σ(F 2)] = 0.058
  • wR(F 2) = 0.138
  • S = 1.10
  • 3433 reflections
  • 193 parameters
  • All H-atom parameters refined
  • Δρmax = 0.45 e Å−3
  • Δρmin = −0.33 e Å−3

Data collection: APEX2 (Bruker, 2005 [triangle]); cell refinement: SAINT (Bruker, 2005 [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/S1600536809050302/lh2960sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809050302/lh2960Isup2.hkl

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

Acknowledgments

HKF and TSH thank Universiti Sains Malaysia (USM) for the Research University Golden Goose Grant (1001/PFIZIK/811012). VV is grateful to the DST-India for funding through the Young Scientist Scheme (Fast Track Proposal).

supplementary crystallographic information

Comment

Pyrazoles are an important class of heterocyclic compounds and many pyrazole derivatives have a broad spectrum of biological activities such as anti-inflammatory (Singh et al., 1978; Tewari & Mishra, 2001), anti-viral (Genin et al., 2000; Storer et al., 1999), anti-tumor (Hsu et al., 1956; Skipper et al., 1955), and herbicidal (Jung et al., 2002; Kudo et al., 1999) activities. Recently urea derivatives of pyrazole been reported as potent inhibitors of P38 kinase (Duma, 2000), On the other hand, pyrazole derivatives are anti-angiogenic agent (Qiao et al., 2003), A3 adenosine receptor antagonist (Baraldi et al., 2003), neuropeptide YY5 receptor antagonists (Stamford & Wu, 2004) and kinase inhibitor for the treatment of type 2 diabetes, hyperlipidemia and obesity (Brown et al., 2004) as well as thrombopiotinmimetics (Heerding, 2003). 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 and 4-chloro substituted phenyl rings in the aromatic part of a 1,5-diaryl pyrazole. As part of our on going research programme aiming at the synthesis of new anti-microbial compounds, herein we report the crystal structure of a novel pyrazole derivative.

In the crystal structure (Fig. 1), the pyrazole ring system (C7/C8/N2/N1/C11) is approximately planar, with a maximum deviation of 0.002 (2) Å for atom C11. The dihedral angle formed between the mean plane of pyrazole ring and the benzene ring (C1–C6) is 66.93 (9)°. The bond lengths (Allen et al., 1987) and angles are within normal ranges and comparable to a closely related structure (Goh et al., 2009).

In the crystal packing (Fig. 2), pairs of intermolecular N2—H1N2···O2i and O3—H1O3···N1ii hydrogen bonds (Table 1) connect neighbouring molecules, into dimers, generating R22(10) and R22(8) ring motifs (Bernstein et al., 1995), respectively. The crystal structure is further stabilized by C—H···π interactions (Table 1), involving the C1–C6 (centroid Cg1) benzene ring.

Experimental

LiHMDS (19.4 ml, 1.0 min THF, 19.4 mmol) was added quickly to the solution of oxyacetic acid ethyl ester (1.0 g, 5.5 mmol) in toluene (15.0 ml) using syringe at 195 K with agitation and the anion formed was allowed to stand for approximately 1 min, and then 2-methoxyacetyl chloride (1.0 ml, 13.8 mmol) was added into the lot with stirring. Reaction mixture was removed from acetone-dry ice bath and stirred for 10 min then acetic acid (2.0 ml) was added with stirring. Ethanol (15.0 ml) and hydrazine hydrate (1.5 ml, 44.0 mmol) was added and refluxed for 10 min. Reaction mixture was concentrated to dryness under reduced pressure and redissolved in ethyl acetate. The organic layer was washed with saturated brine solution, dried over Na2SO4 and evaporated under reduced pressure. Crude product was purified by column chromatography using a mixture of 1:99 methanol and ethylacetate. Pale yellow solid was obtained. Mp. 418.8–419.8 K. Yield: 57%.

Refinement

All hydrogen atoms were located in a difference map and were refined freely. [Range of C—H = 0.94 (2)–1.03 (2) Å].

Figures

Fig. 1.
The molecular structure of the title compound, showing 50% probability displacement ellipsoids and the atom numbering scheme.
Fig. 2.
The crystal packing of the title compound, viewed along a axis. Intermolecular hydrogen bonds are shown by dashed lines.

Crystal data

C11H12N2O3F(000) = 464
Mr = 220.23Dx = 1.355 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 6087 reflections
a = 8.8876 (5) Åθ = 2.3–32.2°
b = 10.3031 (5) ŵ = 0.10 mm1
c = 12.0083 (6) ÅT = 100 K
β = 100.917 (3)°Plate, yellow
V = 1079.7 (1) Å30.69 × 0.57 × 0.18 mm
Z = 4

Data collection

Bruker SMART APEXII CCD area-detector diffractometer3433 independent reflections
Radiation source: fine-focus sealed tube2373 reflections with I > 2σ(I)
graphiteRint = 0.032
[var phi] and ω scansθmax = 31.0°, θmin = 2.3°
Absorption correction: multi-scan (SADABS; Bruker, 2005)h = −12→11
Tmin = 0.934, Tmax = 0.983k = −14→14
14470 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)] = 0.058Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.138All H-atom parameters refined
S = 1.10w = 1/[σ2(Fo2) + (0.0465P)2 + 0.7446P] where P = (Fo2 + 2Fc2)/3
3433 reflections(Δ/σ)max < 0.001
193 parametersΔρmax = 0.45 e Å3
0 restraintsΔρmin = −0.33 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
O10.79382 (13)0.20467 (12)0.25817 (9)0.0209 (3)
O20.84461 (13)0.54359 (11)0.06550 (11)0.0243 (3)
O30.86330 (14)−0.01790 (11)0.10686 (10)0.0210 (3)
N10.97188 (15)0.15166 (12)0.01762 (11)0.0187 (3)
N20.98156 (16)0.28291 (13)0.03420 (12)0.0197 (3)
C10.5751 (2)0.2793 (2)0.32287 (16)0.0313 (4)
C20.4180 (2)0.2854 (2)0.31444 (19)0.0373 (5)
C30.3212 (2)0.2243 (2)0.22663 (17)0.0315 (4)
C40.3817 (2)0.1569 (2)0.14638 (17)0.0339 (4)
C50.5396 (2)0.1508 (2)0.15308 (16)0.0293 (4)
C60.63487 (18)0.21173 (15)0.24200 (13)0.0182 (3)
C70.85883 (17)0.21114 (15)0.16285 (13)0.0178 (3)
C80.91537 (18)0.32155 (15)0.12032 (13)0.0188 (3)
C90.9123 (2)0.46065 (16)0.15618 (14)0.0222 (3)
C100.6866 (2)0.51602 (19)0.02363 (19)0.0310 (4)
C110.89717 (17)0.10779 (15)0.09653 (13)0.0177 (3)
H1A0.644 (3)0.324 (2)0.3821 (19)0.042 (6)*
H2A0.375 (3)0.334 (3)0.368 (2)0.056 (8)*
H3A0.214 (3)0.227 (2)0.2222 (19)0.039 (6)*
H4A0.315 (3)0.112 (3)0.087 (2)0.050 (7)*
H5A0.583 (2)0.106 (2)0.0976 (18)0.033 (6)*
H9A1.017 (2)0.4927 (19)0.1791 (16)0.021 (5)*
H9B0.853 (2)0.466 (2)0.2184 (17)0.028 (5)*
H10A0.678 (2)0.428 (2)−0.0107 (19)0.038 (6)*
H10B0.652 (3)0.582 (3)−0.032 (2)0.047 (7)*
H10C0.625 (3)0.518 (2)0.088 (2)0.041 (6)*
H1N21.038 (2)0.329 (2)−0.0073 (17)0.024 (5)*
H1O30.924 (3)−0.065 (2)0.067 (2)0.047 (7)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0193 (5)0.0261 (6)0.0184 (5)0.0006 (5)0.0062 (4)−0.0018 (4)
O20.0232 (6)0.0139 (6)0.0362 (7)−0.0005 (4)0.0070 (5)0.0036 (5)
O30.0265 (6)0.0133 (5)0.0264 (6)−0.0028 (5)0.0134 (5)−0.0010 (4)
N10.0228 (7)0.0116 (6)0.0232 (6)0.0002 (5)0.0081 (5)0.0000 (5)
N20.0233 (7)0.0131 (6)0.0246 (7)−0.0006 (5)0.0091 (5)0.0009 (5)
C10.0302 (9)0.0340 (11)0.0320 (9)−0.0006 (8)0.0114 (7)−0.0121 (8)
C20.0321 (10)0.0416 (12)0.0431 (11)0.0074 (9)0.0194 (9)−0.0070 (9)
C30.0215 (8)0.0372 (11)0.0378 (10)0.0046 (8)0.0110 (7)0.0117 (8)
C40.0228 (9)0.0446 (12)0.0332 (10)−0.0023 (8)0.0027 (7)−0.0019 (9)
C50.0236 (9)0.0364 (11)0.0286 (9)0.0012 (7)0.0065 (7)−0.0094 (8)
C60.0198 (7)0.0143 (7)0.0220 (7)0.0012 (6)0.0080 (6)0.0024 (6)
C70.0187 (7)0.0175 (7)0.0178 (7)0.0007 (6)0.0051 (5)−0.0002 (6)
C80.0191 (7)0.0154 (7)0.0218 (7)0.0013 (6)0.0038 (6)−0.0012 (6)
C90.0254 (8)0.0153 (8)0.0263 (8)0.0004 (6)0.0056 (6)−0.0022 (6)
C100.0238 (9)0.0213 (9)0.0462 (11)0.0011 (7)0.0020 (8)0.0031 (8)
C110.0181 (7)0.0159 (7)0.0198 (7)−0.0007 (6)0.0054 (5)0.0001 (6)

Geometric parameters (Å, °)

O1—C71.3781 (18)C3—C41.377 (3)
O1—C61.3910 (19)C3—H3A0.94 (2)
O2—C91.425 (2)C4—C51.392 (3)
O2—C101.427 (2)C4—H4A0.96 (3)
O3—C111.3406 (19)C5—C61.382 (2)
O3—H1O30.92 (3)C5—H5A0.95 (2)
N1—C111.335 (2)C7—C81.380 (2)
N1—N21.3672 (19)C7—C111.410 (2)
N2—C81.343 (2)C8—C91.498 (2)
N2—H1N20.91 (2)C9—H9A0.98 (2)
C1—C61.380 (2)C9—H9B0.99 (2)
C1—C21.383 (3)C10—H10A0.99 (2)
C1—H1A0.96 (2)C10—H10B0.96 (3)
C2—C31.380 (3)C10—H10C1.03 (2)
C2—H2A0.95 (3)
C7—O1—C6117.13 (12)C1—C6—O1116.36 (15)
C9—O2—C10113.24 (13)C5—C6—O1122.80 (14)
C11—O3—H1O3107.0 (15)O1—C7—C8125.92 (14)
C11—N1—N2104.93 (13)O1—C7—C11128.09 (14)
C8—N2—N1112.37 (13)C8—C7—C11105.64 (14)
C8—N2—H1N2129.8 (13)N2—C8—C7106.50 (14)
N1—N2—H1N2117.5 (13)N2—C8—C9122.63 (14)
C6—C1—C2119.29 (18)C7—C8—C9130.87 (15)
C6—C1—H1A119.0 (14)O2—C9—C8112.47 (13)
C2—C1—H1A121.7 (14)O2—C9—H9A104.7 (11)
C3—C2—C1120.65 (18)C8—C9—H9A109.7 (11)
C3—C2—H2A119.0 (16)O2—C9—H9B109.6 (12)
C1—C2—H2A120.3 (16)C8—C9—H9B107.9 (12)
C4—C3—C2119.72 (17)H9A—C9—H9B112.5 (16)
C4—C3—H3A119.8 (14)O2—C10—H10A108.6 (13)
C2—C3—H3A120.5 (14)O2—C10—H10B105.4 (14)
C3—C4—C5120.34 (18)H10A—C10—H10B111.7 (19)
C3—C4—H4A119.9 (15)O2—C10—H10C111.1 (13)
C5—C4—H4A119.7 (15)H10A—C10—H10C108.8 (18)
C6—C5—C4119.20 (17)H10B—C10—H10C111.3 (19)
C6—C5—H5A119.6 (13)N1—C11—O3122.92 (14)
C4—C5—H5A121.2 (13)N1—C11—C7110.57 (14)
C1—C6—C5120.79 (16)O3—C11—C7126.51 (14)
C11—N1—N2—C8−0.09 (17)N1—N2—C8—C9179.33 (14)
C6—C1—C2—C30.3 (3)O1—C7—C8—N2173.96 (14)
C1—C2—C3—C4−0.2 (3)C11—C7—C8—N20.26 (17)
C2—C3—C4—C5−0.4 (3)O1—C7—C8—C9−5.4 (3)
C3—C4—C5—C60.9 (3)C11—C7—C8—C9−179.12 (16)
C2—C1—C6—C50.2 (3)C10—O2—C9—C864.02 (19)
C2—C1—C6—O1−177.32 (17)N2—C8—C9—O256.1 (2)
C4—C5—C6—C1−0.7 (3)C7—C8—C9—O2−124.58 (18)
C4—C5—C6—O1176.57 (17)N2—N1—C11—O3179.16 (14)
C7—O1—C6—C1−142.80 (16)N2—N1—C11—C70.26 (17)
C7—O1—C6—C539.8 (2)O1—C7—C11—N1−173.85 (14)
C6—O1—C7—C895.50 (18)C8—C7—C11—N1−0.33 (18)
C6—O1—C7—C11−92.22 (19)O1—C7—C11—O37.3 (3)
N1—N2—C8—C7−0.12 (18)C8—C7—C11—O3−179.19 (15)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N2—H1N2···O2i0.91 (2)1.89 (2)2.7778 (18)165.7 (19)
O3—H1O3···N1ii0.92 (2)1.74 (2)2.6663 (18)176 (2)
C3—H3A···Cg1iii0.94 (2)2.77 (3)2.73147.6 (18)

Symmetry codes: (i) −x+2, −y+1, −z; (ii) −x+2, −y, −z; (iii) x−1, y, z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: LH2960).

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.
  • Baraldi, P. G., Bovero, A., Fruttarolo, F., Romagnoli, R., Tabrizi, M. A., Preti, D., Varani, K., Borea, P. A. & Moorman, A. R. (2003). Bioorg. Med. Chem. 11, 4161–4169. [PubMed]
  • Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555–1573.
  • Brown, M. L., Cheung, M., Dickerson, S. H., Drewy, D. H., Lackey, K. E., Peat, A. J., Thomson, S. A., Veal, J. M. & Wilson, J. L. R. (2004). PCT Int. Appl. WO 20049596.
  • Bruker (2005). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wiscosin, USA.
  • Cosier, J. & Glazer, A. M. (1986). J. Appl. Cryst. 19, 105–107.
  • Duma, J., Hatoum-Mokdad, H., Sibley, R., Riedl, B., Scott, W. J., Monahan, M. K., Lowinger, T. B., Brennan, C., Natero, R., Turner, T., Johnson, J. S., Schoenlebar, R., Bhargava, A., Wilhelm, S. M., Housley, T. J., Ranges, G. E. & Shrikhande, A. (2000). Bioorg. Med. Chem. Lett. 10, 2051–2054.
  • Genin, M. J., Biles, C., Keiser, B. J., Poppe, S. M., Swaney, S. M., Tarpley, W. G., Yagi, Y. & Romero, D. L. (2000). J. Med. Chem. 43, 1034–1040.
  • Goh, J. H., Fun, H.-K., Nithinchandra, & Kalluraya, B. (2009). Acta Cryst. E65, o3088–o3089. [PMC free article] [PubMed]
  • Heerding, D. A. (2003). PCT Int. Appl. WO, 2003103686.
  • Hsu, T. C., Robins, R. K. & Cheng, C. C. (1956). Science, 13, 848–868.
  • Jung, J. C., Walkins, E. B. & Avery, M. A. (2002). Tetrahedron, 58, 3039–3049.
  • Kudo, N., Furuta, S., Taniguchi, M., Endo, T. & Sato, K. (1999). Chem. Pharm. Bull. 47, 857–868.
  • Qiao, J. X., Pinto, D. J., Orwat, M. J., Han, W. & Friedrich, S. R. (2003). PCT Int. Appl. WO, 200399276.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Singh, S. P., Prakash, O., Tomer, R. K. & Sawhney, S. N. (1978). Indian J. Chem. Sect. B, 16, 733–735.
  • Skipper, H. E., Robins, R. K. & Thompson, J. R. (1955). Proc. Soc. Exp. Bio. Med. 89, 589–594.
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]
  • Stamford, A. W. & Wu, Y. (2004). PCT Int. Appl. WO 20045262.
  • Storer, R., Ashton, C. J., Baxter, A. D., Hann, M. M., Marr, C. L. P., Mason, A. M., Mo, C. L., Myers, P. L., Noble, S. A., Penn, H. R., Weir, N. G., Niall, G., Woods, J. M. & Coe, P. L. (1999). Nucleosides Nucleotides, 18, 203–216.
  • Tewari, A. K. & Mishra, A. (2001). Bioorg. Med. Chem. 9, 715–718. [PubMed]

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