organic compounds
2-[(E)-(3,4-Dimethylisoxazol-5-yl)iminomethyl]phenol
aX-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia, and bDepartment of Chemistry, Faculty of Science, King Abdu Aziz University, Jeddah, Saudi Arabia
*Correspondence e-mail: hkfun@usm.my
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); 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
Crystal data
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Refinement
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Data collection: APEX2 (Bruker, 2009); cell SAINT (Bruker, 2009); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009).
Supporting information
10.1107/S1600536810008160/sj2738sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536810008160/sj2738Isup2.hkl
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).
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).
Data collection: APEX2 (Bruker, 2009); cell
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).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). |
C12H12N2O2 | Z = 2 |
Mr = 216.24 | F(000) = 228 |
Triclinic, P1 | Dx = 1.307 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 5.3475 (14) Å | Cell parameters from 2862 reflections |
b = 8.615 (2) Å | θ = 2.4–29.7° |
c = 12.321 (3) Å | µ = 0.09 mm−1 |
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 |
Bruker APEX DUO CCD area-detector diffractometer | 2467 independent reflections |
Radiation source: fine-focus sealed tube | 1946 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.000 |
ϕ and ω scans | θmax = 27.5°, θmin = 1.7° |
Absorption correction: multi-scan (SADABS; Bruker, 2009) | h = −6→6 |
Tmin = 0.951, Tmax = 0.993 | k = −11→10 |
2467 measured reflections | l = −6→15 |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.070 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.203 | H 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 parameters | Δρmax = 0.40 e Å−3 |
0 restraints | Δρmin = −0.34 e Å−3 |
C12H12N2O2 | γ = 94.059 (5)° |
Mr = 216.24 | V = 549.6 (2) Å3 |
Triclinic, P1 | Z = 2 |
a = 5.3475 (14) Å | Mo Kα radiation |
b = 8.615 (2) Å | µ = 0.09 mm−1 |
c = 12.321 (3) Å | T = 100 K |
α = 103.696 (5)° | 0.56 × 0.14 × 0.08 mm |
β = 91.486 (5)° |
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 = 0.993 | Rint = 0.000 |
2467 measured reflections |
R[F2 > 2σ(F2)] = 0.070 | 0 restraints |
wR(F2) = 0.203 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.06 | Δρmax = 0.40 e Å−3 |
2467 reflections | Δρmin = −0.34 e Å−3 |
152 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
O1 | 1.0387 (4) | 1.1305 (2) | 0.41739 (17) | 0.0228 (5) | |
O2 | 0.6135 (4) | 0.7350 (3) | 0.08828 (18) | 0.0262 (5) | |
N1 | 0.8330 (5) | 0.9521 (3) | 0.2591 (2) | 0.0194 (5) | |
N2 | 1.2481 (5) | 1.2478 (3) | 0.4414 (2) | 0.0252 (6) | |
C1 | 0.2930 (5) | 0.7387 (3) | 0.3499 (3) | 0.0201 (6) | |
H1A | 0.3082 | 0.7892 | 0.4256 | 0.024* | |
C2 | 0.0960 (5) | 0.6240 (3) | 0.3108 (3) | 0.0221 (6) | |
H2A | −0.0224 | 0.5990 | 0.3593 | 0.026* | |
C3 | 0.0782 (6) | 0.5468 (4) | 0.1976 (3) | 0.0249 (7) | |
H3A | −0.0529 | 0.4691 | 0.1710 | 0.030* | |
C4 | 0.2512 (6) | 0.5831 (4) | 0.1235 (3) | 0.0250 (7) | |
H4A | 0.2362 | 0.5296 | 0.0484 | 0.030* | |
C5 | 0.4491 (5) | 0.7008 (3) | 0.1626 (2) | 0.0199 (6) | |
C6 | 0.4711 (5) | 0.7802 (3) | 0.2771 (2) | 0.0186 (6) | |
C7 | 0.6723 (5) | 0.9024 (3) | 0.3225 (2) | 0.0191 (6) | |
H7A | 0.6859 | 0.9462 | 0.3992 | 0.023* | |
C8 | 1.0225 (5) | 1.0682 (3) | 0.3052 (2) | 0.0176 (6) | |
C9 | 1.2091 (5) | 1.1366 (3) | 0.2539 (2) | 0.0192 (6) | |
C10 | 1.3428 (5) | 1.2479 (3) | 0.3446 (2) | 0.0195 (6) | |
C11 | 1.2629 (6) | 1.1010 (4) | 0.1327 (3) | 0.0276 (7) | |
H11A | 1.1457 | 1.0163 | 0.0921 | 0.041* | |
H11C | 1.4305 | 1.0685 | 0.1229 | 0.041* | |
H11D | 1.2470 | 1.1953 | 0.1051 | 0.041* | |
C12 | 1.5687 (5) | 1.3582 (4) | 0.3386 (3) | 0.0243 (7) | |
H12A | 1.6191 | 1.4202 | 0.4124 | 0.036* | |
H12D | 1.5285 | 1.4287 | 0.2920 | 0.036* | |
H12B | 1.7034 | 1.2963 | 0.3075 | 0.036* | |
H1O2 | 0.722 (11) | 0.820 (7) | 0.132 (5) | 0.080 (18)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0194 (11) | 0.0238 (11) | 0.0233 (11) | −0.0060 (8) | 0.0019 (8) | 0.0042 (8) |
O2 | 0.0250 (12) | 0.0281 (11) | 0.0232 (11) | −0.0040 (9) | 0.0061 (9) | 0.0028 (9) |
N1 | 0.0170 (12) | 0.0148 (11) | 0.0261 (13) | 0.0009 (9) | 0.0020 (9) | 0.0041 (9) |
N2 | 0.0207 (13) | 0.0246 (13) | 0.0290 (14) | −0.0061 (10) | −0.0003 (10) | 0.0062 (10) |
C1 | 0.0155 (14) | 0.0176 (13) | 0.0270 (15) | 0.0054 (10) | 0.0036 (11) | 0.0036 (11) |
C2 | 0.0152 (14) | 0.0204 (14) | 0.0318 (16) | 0.0021 (11) | 0.0054 (11) | 0.0078 (12) |
C3 | 0.0159 (14) | 0.0225 (14) | 0.0353 (17) | −0.0013 (11) | −0.0012 (12) | 0.0063 (12) |
C4 | 0.0247 (16) | 0.0227 (15) | 0.0246 (15) | −0.0006 (12) | −0.0007 (12) | 0.0004 (12) |
C5 | 0.0164 (14) | 0.0194 (14) | 0.0242 (14) | 0.0026 (11) | 0.0021 (11) | 0.0052 (11) |
C6 | 0.0154 (13) | 0.0155 (13) | 0.0256 (14) | 0.0033 (10) | 0.0019 (11) | 0.0054 (11) |
C7 | 0.0199 (14) | 0.0158 (13) | 0.0216 (14) | 0.0058 (11) | 0.0019 (11) | 0.0034 (10) |
C8 | 0.0140 (13) | 0.0163 (13) | 0.0237 (14) | 0.0051 (10) | 0.0029 (10) | 0.0056 (10) |
C9 | 0.0159 (13) | 0.0169 (13) | 0.0262 (15) | 0.0037 (10) | 0.0033 (11) | 0.0074 (11) |
C10 | 0.0136 (13) | 0.0169 (13) | 0.0296 (15) | 0.0038 (10) | 0.0020 (11) | 0.0079 (11) |
C11 | 0.0272 (16) | 0.0291 (16) | 0.0260 (16) | 0.0009 (13) | 0.0080 (12) | 0.0055 (12) |
C12 | 0.0137 (13) | 0.0215 (14) | 0.0392 (17) | 0.0005 (11) | 0.0038 (12) | 0.0100 (12) |
O1—C8 | 1.357 (3) | C4—H4A | 0.9300 |
O1—N2 | 1.429 (3) | C5—C6 | 1.412 (4) |
O2—C5 | 1.353 (4) | C6—C7 | 1.452 (4) |
O2—H1O2 | 0.95 (6) | C7—H7A | 0.9300 |
N1—C7 | 1.293 (4) | C8—C9 | 1.367 (4) |
N1—C8 | 1.381 (4) | C9—C10 | 1.426 (4) |
N2—C10 | 1.308 (4) | C9—C11 | 1.491 (4) |
C1—C2 | 1.385 (4) | C10—C12 | 1.498 (4) |
C1—C6 | 1.410 (4) | C11—H11A | 0.9600 |
C1—H1A | 0.9300 | C11—H11C | 0.9600 |
C2—C3 | 1.394 (4) | C11—H11D | 0.9600 |
C2—H2A | 0.9300 | C12—H12A | 0.9600 |
C3—C4 | 1.387 (4) | C12—H12D | 0.9600 |
C3—H3A | 0.9300 | C12—H12B | 0.9600 |
C4—C5 | 1.404 (4) | ||
C8—O1—N2 | 107.7 (2) | N1—C7—H7A | 119.1 |
C5—O2—H1O2 | 103 (3) | C6—C7—H7A | 119.1 |
C7—N1—C8 | 120.3 (2) | O1—C8—C9 | 110.8 (2) |
C10—N2—O1 | 105.3 (2) | O1—C8—N1 | 119.7 (2) |
C2—C1—C6 | 121.2 (3) | C9—C8—N1 | 129.5 (3) |
C2—C1—H1A | 119.4 | C8—C9—C10 | 103.2 (3) |
C6—C1—H1A | 119.4 | C8—C9—C11 | 128.4 (3) |
C1—C2—C3 | 118.9 (3) | C10—C9—C11 | 128.4 (3) |
C1—C2—H2A | 120.6 | N2—C10—C9 | 112.9 (3) |
C3—C2—H2A | 120.6 | N2—C10—C12 | 119.8 (3) |
C4—C3—C2 | 121.6 (3) | C9—C10—C12 | 127.3 (3) |
C4—C3—H3A | 119.2 | C9—C11—H11A | 109.5 |
C2—C3—H3A | 119.2 | C9—C11—H11C | 109.5 |
C3—C4—C5 | 119.7 (3) | H11A—C11—H11C | 109.5 |
C3—C4—H4A | 120.2 | C9—C11—H11D | 109.5 |
C5—C4—H4A | 120.2 | H11A—C11—H11D | 109.5 |
O2—C5—C4 | 118.4 (3) | H11C—C11—H11D | 109.5 |
O2—C5—C6 | 121.9 (3) | C10—C12—H12A | 109.5 |
C4—C5—C6 | 119.6 (3) | C10—C12—H12D | 109.5 |
C1—C6—C5 | 119.0 (3) | H12A—C12—H12D | 109.5 |
C1—C6—C7 | 118.8 (3) | C10—C12—H12B | 109.5 |
C5—C6—C7 | 122.2 (3) | H12A—C12—H12B | 109.5 |
N1—C7—C6 | 121.8 (3) | H12D—C12—H12B | 109.5 |
C8—O1—N2—C10 | −0.3 (3) | N2—O1—C8—C9 | 0.3 (3) |
C6—C1—C2—C3 | 1.3 (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—C6 | 0.5 (4) | N1—C8—C9—C10 | 179.4 (3) |
C2—C1—C6—C5 | −1.1 (4) | O1—C8—C9—C11 | 178.7 (3) |
C2—C1—C6—C7 | 179.4 (3) | N1—C8—C9—C11 | −1.7 (5) |
O2—C5—C6—C1 | 180.0 (3) | O1—N2—C10—C9 | 0.1 (3) |
C4—C5—C6—C1 | 0.2 (4) | O1—N2—C10—C12 | −179.8 (2) |
O2—C5—C6—C7 | −0.5 (4) | C8—C9—C10—N2 | 0.0 (3) |
C4—C5—C6—C7 | 179.7 (3) | C11—C9—C10—N2 | −178.9 (3) |
C8—N1—C7—C6 | −179.7 (2) | C8—C9—C10—C12 | 180.0 (3) |
C1—C6—C7—N1 | −176.1 (3) | C11—C9—C10—C12 | 1.1 (5) |
C5—C6—C7—N1 | 4.4 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
O2—H1O2···N1 | 1.00 (9) | 1.71 (8) | 2.648 (5) | 154 (8) |
Experimental details
Crystal data | |
Chemical formula | C12H12N2O2 |
Mr | 216.24 |
Crystal system, space group | Triclinic, 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) |
V (Å3) | 549.6 (2) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.56 × 0.14 × 0.08 |
Data collection | |
Diffractometer | Bruker APEX DUO CCD area-detector diffractometer |
Absorption correction | Multi-scan (SADABS; Bruker, 2009) |
Tmin, Tmax | 0.951, 0.993 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 2467, 2467, 1946 |
Rint | 0.000 |
(sin θ/λ)max (Å−1) | 0.649 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.070, 0.203, 1.06 |
No. of reflections | 2467 |
No. of parameters | 152 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.40, −0.34 |
Computer programs: APEX2 (Bruker, 2009), SAINT (Bruker, 2009), SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).
D—H···A | D—H | H···A | D···A | D—H···A |
O2—H1O2···N1 | 1.00 (9) | 1.71 (8) | 2.648 (5) | 154 (8) |
Acknowledgements
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.
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This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
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).