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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).

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536810008160/sj2738sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S1600536810008160/sj2738Isup2.hkl
Contains datablock I

CCDC reference: 774231

Key indicators

  • Single-crystal X-ray study
  • T = 100 K
  • Mean [sigma](C-C) = 0.004 Å
  • R factor = 0.070
  • wR factor = 0.203
  • Data-to-parameter ratio = 16.2

checkCIF/PLATON results

No syntax errors found



Alert level C PLAT222_ALERT_3_C Large Non-Solvent H Ueq(max)/Ueq(min) ... 3.48 Ratio PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L= 0.600 43 PLAT912_ALERT_4_C Missing # of FCF Reflections Above STh/L= 0.600 2
Alert level G PLAT154_ALERT_1_G The su's on the Cell Angles are Equal (x 10000) 500 Deg. PLAT380_ALERT_4_G Check Incorrectly? Oriented X(sp2)-Methyl Moiety C12 PLAT720_ALERT_4_G Number of Unusual/Non-Standard Labels .......... 1 PLAT931_ALERT_5_G Check Twin Law ( 0 0 1)[ ] Estimated BASF 0.17
0 ALERT level A = In general: serious problem 0 ALERT level B = Potentially serious problem 3 ALERT level C = Check and explain 4 ALERT level G = General alerts; check 1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 0 ALERT type 2 Indicator that the structure model may be wrong or deficient 2 ALERT type 3 Indicator that the structure quality may be low 3 ALERT type 4 Improvement, methodology, query or suggestion 1 ALERT type 5 Informative message, check

Comment top

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 C7N1 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).

Related literature top

For background to the biological and pharmacological properties of oxazole derivatives, see: Spinelli (1999); Conti et al. (1998); Mishra et al. (1998); Ko et al. (1998); Kang et al. (2000); Huang & Chen (2005). For details of hydrogen bonding and hydrogen-bond motifs see: Jeffrey & Saenger (1991); Bernstein et al. (1995); Jeffrey (1997); Scheiner (1997). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986).

Experimental top

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 (CO), 1562 (CC), 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 top

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).

Computing details top

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

Figures top
[Figure 1] Fig. 1. The asymmetric unit of the title compound, showing 50% probability displacement ellipsoids and the atom-numbering scheme.
[Figure 2] Fig. 2. The crystal packing of the title compound (I).
2-[(E)-(3,4-Dimethylisoxazol-5-yl)iminomethyl]phenol top
Crystal data top
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 top
Bruker APEX DUO CCD area-detector
diffractometer
2467 independent reflections
Radiation source: fine-focus sealed tube1946 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.000
ϕ and ω scansθmax = 27.5°, θmin = 1.7°
Absorption correction: multi-scan
(SADABS; Bruker, 2009)
h = 66
Tmin = 0.951, Tmax = 0.993k = 1110
2467 measured reflectionsl = 615
Refinement top
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 = 1.06 w = 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
Crystal data top
C12H12N2O2γ = 94.059 (5)°
Mr = 216.24V = 549.6 (2) Å3
Triclinic, P1Z = 2
a = 5.3475 (14) ÅMo Kα radiation
b = 8.615 (2) ŵ = 0.09 mm1
c = 12.321 (3) ÅT = 100 K
α = 103.696 (5)°0.56 × 0.14 × 0.08 mm
β = 91.486 (5)°
Data collection top
Bruker APEX DUO CCD area-detector
diffractometer
2467 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2009)
1946 reflections with I > 2σ(I)
Tmin = 0.951, Tmax = 0.993Rint = 0.000
2467 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0700 restraints
wR(F2) = 0.203H atoms treated by a mixture of independent and constrained refinement
S = 1.06Δρmax = 0.40 e Å3
2467 reflectionsΔρmin = 0.34 e Å3
152 parameters
Special details top

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) top
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)
H2A0.02240.59900.35930.026*
C30.0782 (6)0.5468 (4)0.1976 (3)0.0249 (7)
H3A0.05290.46910.17100.030*
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) top
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, º) top
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—C100.3 (3)N2—O1—C8—C90.3 (3)
C6—C1—C2—C31.3 (4)N2—O1—C8—N1179.4 (2)
C1—C2—C3—C40.6 (5)C7—N1—C8—O10.3 (4)
C2—C3—C4—C50.3 (5)C7—N1—C8—C9179.9 (3)
C3—C4—C5—O2179.3 (3)O1—C8—C9—C100.2 (3)
C3—C4—C5—C60.5 (4)N1—C8—C9—C10179.4 (3)
C2—C1—C6—C51.1 (4)O1—C8—C9—C11178.7 (3)
C2—C1—C6—C7179.4 (3)N1—C8—C9—C111.7 (5)
O2—C5—C6—C1180.0 (3)O1—N2—C10—C90.1 (3)
C4—C5—C6—C10.2 (4)O1—N2—C10—C12179.8 (2)
O2—C5—C6—C70.5 (4)C8—C9—C10—N20.0 (3)
C4—C5—C6—C7179.7 (3)C11—C9—C10—N2178.9 (3)
C8—N1—C7—C6179.7 (2)C8—C9—C10—C12180.0 (3)
C1—C6—C7—N1176.1 (3)C11—C9—C10—C121.1 (5)
C5—C6—C7—N14.4 (4)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O2—H1O2···N11.00 (9)1.71 (8)2.648 (5)154 (8)

Experimental details

Crystal data
Chemical formulaC12H12N2O2
Mr216.24
Crystal system, space groupTriclinic, P1
Temperature (K)100
a, b, c (Å)5.3475 (14), 8.615 (2), 12.321 (3)
α, β, γ (°)103.696 (5), 91.486 (5), 94.059 (5)
V3)549.6 (2)
Z2
Radiation typeMo Kα
µ (mm1)0.09
Crystal size (mm)0.56 × 0.14 × 0.08
Data collection
DiffractometerBruker APEX DUO CCD area-detector
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2009)
Tmin, Tmax0.951, 0.993
No. of measured, independent and
observed [I > 2σ(I)] reflections
2467, 2467, 1946
Rint0.000
(sin θ/λ)max1)0.649
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.070, 0.203, 1.06
No. of reflections2467
No. of parameters152
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.40, 0.34

Computer programs: APEX2 (Bruker, 2009), SAINT (Bruker, 2009), SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O2—H1O2···N11.00 (9)1.71 (8)2.648 (5)154 (8)
 

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