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Acta Crystallogr Sect E Struct Rep Online. 2010 April 1; 66(Pt 4): o773–o774.
Published online 2010 March 6. doi:  10.1107/S1600536810008160
PMCID: PMC2983993

2-[(E)-(3,4-Dimethyl­isoxazol-5-yl)imino­meth­yl]phenol

Abstract

The title compound, C12H12N2O2, has been synthesized by the reaction of 5-amino-3,4-dimethyl­isoxazole and salicyladehyde. The mol­ecule adopts an E configuration about the central C=N double bond. The dihedral angle between the isoxazole and phenyl rings is 4.2 (2)° and an intra­molecular O—H(...)N hydrogen bond generates an S(6) ring motif. The crystal studied was a non-merohedral twin with a domain ratio of 0.834 (4):0.166 (4).

Related literature

For background to the biological and pharmacological properties of oxazole derivatives, see: Spinelli (1999 [triangle]); Conti et al. (1998 [triangle]); Mishra et al. (1998 [triangle]); Ko et al. (1998 [triangle]); Kang et al. (2000 [triangle]); Huang & Chen (2005 [triangle]). For details of hydrogen bonding and hydrogen-bond motifs, see: Jeffrey & Saenger (1991 [triangle]); Bernstein et al. (1995 [triangle]); Jeffrey (1997 [triangle]); Scheiner (1997 [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-66-0o773-scheme1.jpg

Experimental

Crystal data

  • C12H12N2O2
  • M r = 216.24
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-0o773-efi1.jpg
  • a = 5.3475 (14) Å
  • b = 8.615 (2) Å
  • c = 12.321 (3) Å
  • α = 103.696 (5)°
  • β = 91.486 (5)°
  • γ = 94.059 (5)°
  • V = 549.6 (2) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 100 K
  • 0.56 × 0.14 × 0.08 mm

Data collection

  • Bruker APEX DUO CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2009 [triangle]) T min = 0.951, T max = 0.993
  • 2467 measured reflections
  • 2467 independent reflections
  • 1946 reflections with I > 2σ(I)

Refinement

  • R[F 2 > 2σ(F 2)] = 0.070
  • wR(F 2) = 0.203
  • S = 1.06
  • 2467 reflections
  • 152 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.40 e Å−3
  • Δρmin = −0.34 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/S1600536810008160/sj2738sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810008160/sj2738Isup2.hkl

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

Acknowledgments

HKF and MH thank the Malaysian Government and Universiti Sains Malaysia for the Research University Golden Goose grant No. 1001/PFIZIK/811012. MH thanks Universiti Sains Malaysia for a post-doctoral research fellowship. AMA, SAK and KAK thank the Chemistry Department, King Abdul Aziz University, Jeddah, Saudi Arabia, for providing research facilities. AMA would also like to thank the deanship of scientific research at KAU for grant No. 171/428.

supplementary crystallographic information

Comment

Heterocyclic compounds, especially isoxazoles, are one of the key building elements of natural products. Among the numerous heterocyclic systems of biological and pharmacological interest, the oxazole ring is endowed with various activities, including hypoglycemic (Spinelli, 1999), analgesic (Conti et al., 1998), anti-inflammatory (Mishra et al., 1998), anti-bacterial (Ko et al., 1998) and anti-tumor (Kang et al., 2000) properties. In view of the importance of the title compound as a pharmaceutical intermediate, the paper reports its synthesis and crystal structure.

In the title compound (Fig. 1), the isoxazole ring is essentially planar with a maximum deviation of 0.002 (2) Å for atom C8. The dihedral angle between the isoxazole ring (N2/O1/C8–C10) and the phenyl ring (C1–C6) is 4.30 (15)°. The methyl groups at C9 and C10 deviate from the isoxazole mean plane by 0.056 (3) Å and 0.013 (4) Å , respectively. The C5—O2 and C7═N1 bond lengths are 1.353 (4) Å and 1.293 (4) Å, respectively, and agree with the corresponding values in 4-{[(1E)-(3,5-dibromo-2-hydroxyphenyl) methylene]-amino}-1,5-dimethyl-2-phenyl-1,2-dihydro- 3H-pyrazol-3-one [1.344 (3) and 1.292 (4) Å; Huang & Chen, 2005].

In the crystal structure (Fig. 2), the imino N atoms are linked to the phenol O atoms and act as hydrogen-bond acceptors in intramolecular O2—H1O2···N1 interactions (Table 1) (Jeffrey & Saenger, 1991; Jeffrey, 1997; Scheiner, 1997), which generate S(6) ring motifs (Bernstein et al., 1995).

Experimental

A mixture of 5-amino-3,4-dimethylisoxazole (0.50g, 0.0044 mol) and salicyladehyde (0.54g, 0.0044 mol) in methanol (15 mL) was refluxed for 5 h with stirring to give a light yellow precipitate. It was then filtered and washed with methanol to gives the pure Schiff base. Yield: 68%; mp. 116°C. IR (KBr) vmax cm-1: 2922(C—H), 1594 (C═O), 1562 (C═C), 1152 (C—N). 1H NMR (CDCl3) d: 8.89 (s, 1H, CH olefinic), 7.42 (d, H3, J=1.8Hz), 7.44 (dd, H4, J=7.8Hz), 7.02 (dd, H5, J=7.8Hz), 6.97 (d, H6, J=1.2 Hz), 2.25 (s, CH3), 2.05 (s, CH3).

Refinement

Atom H1O2 was located from the difference Fourier map and refined freely. The remaining hydrogen atoms were positioned geometrically [C–H = 0.93 Å or 0.96 Å] and were refined using a riding model, with Uiso(H) = 1.2 or 1.5 Ueq(C). A rotating group model was applied to the methyl groups. The crystal is a non-merohedral twin with BASF = 0.166 (4).

Figures

Fig. 1.
The asymmetric unit of the title compound, showing 50% probability displacement ellipsoids and the atom-numbering scheme.
Fig. 2.
The crystal packing of the title compound (I).

Crystal data

C12H12N2O2Z = 2
Mr = 216.24F(000) = 228
Triclinic, P1Dx = 1.307 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 5.3475 (14) ÅCell parameters from 2862 reflections
b = 8.615 (2) Åθ = 2.4–29.7°
c = 12.321 (3) ŵ = 0.09 mm1
α = 103.696 (5)°T = 100 K
β = 91.486 (5)°Plate, yellow
γ = 94.059 (5)°0.56 × 0.14 × 0.08 mm
V = 549.6 (2) Å3

Data collection

Bruker APEX DUO CCD area-detector diffractometer2467 independent reflections
Radiation source: fine-focus sealed tube1946 reflections with I > 2σ(I)
graphiteRint = 0.0000
[var phi] and ω scansθmax = 27.5°, θmin = 1.7°
Absorption correction: multi-scan (SADABS; Bruker, 2009)h = −6→6
Tmin = 0.951, Tmax = 0.993k = −11→10
2467 measured reflectionsl = −6→15

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)] = 0.070Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.203H atoms treated by a mixture of independent and constrained refinement
S = 1.06w = 1/[σ2(Fo2) + (0.0657P)2 + 1.1217P] where P = (Fo2 + 2Fc2)/3
2467 reflections(Δ/σ)max = 0.001
152 parametersΔρmax = 0.40 e Å3
0 restraintsΔρmin = −0.34 e Å3

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K.
Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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
O11.0387 (4)1.1305 (2)0.41739 (17)0.0228 (5)
O20.6135 (4)0.7350 (3)0.08828 (18)0.0262 (5)
N10.8330 (5)0.9521 (3)0.2591 (2)0.0194 (5)
N21.2481 (5)1.2478 (3)0.4414 (2)0.0252 (6)
C10.2930 (5)0.7387 (3)0.3499 (3)0.0201 (6)
H1A0.30820.78920.42560.024*
C20.0960 (5)0.6240 (3)0.3108 (3)0.0221 (6)
H2A−0.02240.59900.35930.026*
C30.0782 (6)0.5468 (4)0.1976 (3)0.0249 (7)
H3A−0.05290.46910.17100.030*
C40.2512 (6)0.5831 (4)0.1235 (3)0.0250 (7)
H4A0.23620.52960.04840.030*
C50.4491 (5)0.7008 (3)0.1626 (2)0.0199 (6)
C60.4711 (5)0.7802 (3)0.2771 (2)0.0186 (6)
C70.6723 (5)0.9024 (3)0.3225 (2)0.0191 (6)
H7A0.68590.94620.39920.023*
C81.0225 (5)1.0682 (3)0.3052 (2)0.0176 (6)
C91.2091 (5)1.1366 (3)0.2539 (2)0.0192 (6)
C101.3428 (5)1.2479 (3)0.3446 (2)0.0195 (6)
C111.2629 (6)1.1010 (4)0.1327 (3)0.0276 (7)
H11A1.14571.01630.09210.041*
H11C1.43051.06850.12290.041*
H11D1.24701.19530.10510.041*
C121.5687 (5)1.3582 (4)0.3386 (3)0.0243 (7)
H12A1.61911.42020.41240.036*
H12D1.52851.42870.29200.036*
H12B1.70341.29630.30750.036*
H1O20.722 (11)0.820 (7)0.132 (5)0.080 (18)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0194 (11)0.0238 (11)0.0233 (11)−0.0060 (8)0.0019 (8)0.0042 (8)
O20.0250 (12)0.0281 (11)0.0232 (11)−0.0040 (9)0.0061 (9)0.0028 (9)
N10.0170 (12)0.0148 (11)0.0261 (13)0.0009 (9)0.0020 (9)0.0041 (9)
N20.0207 (13)0.0246 (13)0.0290 (14)−0.0061 (10)−0.0003 (10)0.0062 (10)
C10.0155 (14)0.0176 (13)0.0270 (15)0.0054 (10)0.0036 (11)0.0036 (11)
C20.0152 (14)0.0204 (14)0.0318 (16)0.0021 (11)0.0054 (11)0.0078 (12)
C30.0159 (14)0.0225 (14)0.0353 (17)−0.0013 (11)−0.0012 (12)0.0063 (12)
C40.0247 (16)0.0227 (15)0.0246 (15)−0.0006 (12)−0.0007 (12)0.0004 (12)
C50.0164 (14)0.0194 (14)0.0242 (14)0.0026 (11)0.0021 (11)0.0052 (11)
C60.0154 (13)0.0155 (13)0.0256 (14)0.0033 (10)0.0019 (11)0.0054 (11)
C70.0199 (14)0.0158 (13)0.0216 (14)0.0058 (11)0.0019 (11)0.0034 (10)
C80.0140 (13)0.0163 (13)0.0237 (14)0.0051 (10)0.0029 (10)0.0056 (10)
C90.0159 (13)0.0169 (13)0.0262 (15)0.0037 (10)0.0033 (11)0.0074 (11)
C100.0136 (13)0.0169 (13)0.0296 (15)0.0038 (10)0.0020 (11)0.0079 (11)
C110.0272 (16)0.0291 (16)0.0260 (16)0.0009 (13)0.0080 (12)0.0055 (12)
C120.0137 (13)0.0215 (14)0.0392 (17)0.0005 (11)0.0038 (12)0.0100 (12)

Geometric parameters (Å, °)

O1—C81.357 (3)C4—H4A0.9300
O1—N21.429 (3)C5—C61.412 (4)
O2—C51.353 (4)C6—C71.452 (4)
O2—H1O20.95 (6)C7—H7A0.9300
N1—C71.293 (4)C8—C91.367 (4)
N1—C81.381 (4)C9—C101.426 (4)
N2—C101.308 (4)C9—C111.491 (4)
C1—C21.385 (4)C10—C121.498 (4)
C1—C61.410 (4)C11—H11A0.9600
C1—H1A0.9300C11—H11C0.9600
C2—C31.394 (4)C11—H11D0.9600
C2—H2A0.9300C12—H12A0.9600
C3—C41.387 (4)C12—H12D0.9600
C3—H3A0.9300C12—H12B0.9600
C4—C51.404 (4)
C8—O1—N2107.7 (2)N1—C7—H7A119.1
C5—O2—H1O2103 (3)C6—C7—H7A119.1
C7—N1—C8120.3 (2)O1—C8—C9110.8 (2)
C10—N2—O1105.3 (2)O1—C8—N1119.7 (2)
C2—C1—C6121.2 (3)C9—C8—N1129.5 (3)
C2—C1—H1A119.4C8—C9—C10103.2 (3)
C6—C1—H1A119.4C8—C9—C11128.4 (3)
C1—C2—C3118.9 (3)C10—C9—C11128.4 (3)
C1—C2—H2A120.6N2—C10—C9112.9 (3)
C3—C2—H2A120.6N2—C10—C12119.8 (3)
C4—C3—C2121.6 (3)C9—C10—C12127.3 (3)
C4—C3—H3A119.2C9—C11—H11A109.5
C2—C3—H3A119.2C9—C11—H11C109.5
C3—C4—C5119.7 (3)H11A—C11—H11C109.5
C3—C4—H4A120.2C9—C11—H11D109.5
C5—C4—H4A120.2H11A—C11—H11D109.5
O2—C5—C4118.4 (3)H11C—C11—H11D109.5
O2—C5—C6121.9 (3)C10—C12—H12A109.5
C4—C5—C6119.6 (3)C10—C12—H12D109.5
C1—C6—C5119.0 (3)H12A—C12—H12D109.5
C1—C6—C7118.8 (3)C10—C12—H12B109.5
C5—C6—C7122.2 (3)H12A—C12—H12B109.5
N1—C7—C6121.8 (3)H12D—C12—H12B109.5
C8—O1—N2—C10−0.3 (3)N2—O1—C8—C90.3 (3)
C6—C1—C2—C31.3 (4)N2—O1—C8—N1−179.4 (2)
C1—C2—C3—C4−0.6 (5)C7—N1—C8—O1−0.3 (4)
C2—C3—C4—C5−0.3 (5)C7—N1—C8—C9−179.9 (3)
C3—C4—C5—O2−179.3 (3)O1—C8—C9—C10−0.2 (3)
C3—C4—C5—C60.5 (4)N1—C8—C9—C10179.4 (3)
C2—C1—C6—C5−1.1 (4)O1—C8—C9—C11178.7 (3)
C2—C1—C6—C7179.4 (3)N1—C8—C9—C11−1.7 (5)
O2—C5—C6—C1180.0 (3)O1—N2—C10—C90.1 (3)
C4—C5—C6—C10.2 (4)O1—N2—C10—C12−179.8 (2)
O2—C5—C6—C7−0.5 (4)C8—C9—C10—N20.0 (3)
C4—C5—C6—C7179.7 (3)C11—C9—C10—N2−178.9 (3)
C8—N1—C7—C6−179.7 (2)C8—C9—C10—C12180.0 (3)
C1—C6—C7—N1−176.1 (3)C11—C9—C10—C121.1 (5)
C5—C6—C7—N14.4 (4)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O2—H1O2···N11.00 (9)1.71 (8)2.648 (5)154 (8)

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: SJ2738).

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