Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807031674/hj3042sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807031674/hj3042Isup2.hkl |
CCDC reference: 659094
An oven-dried Schlenk flask was charged with 2,3,4-Trimethoxybenzaldehyde (196 mg, 1.0 mmol), N-tert-butyl hydroxylamine acetate (298 mg, 2.0 mmol) and anhydrous magnesium sulfate (362 mg, 3.0 mmol) under argon. Triethylamine (350 µL, 253 mg, 2.5 mmol) was then added via syringe followed by anhydrous benzene (6 ml, distilled from sodium/benzophenone). After stirring at 90°C in a Schlenk flask for 8 days, the reaction mixture was filtered to remove the magnesium sulfate and the filtrate concentrated to dryness with a rotary evaporator. The crude mixture was purified by flash column chromatography on silica gel (60 230–400 mesh) using neat ethyl acetate as the eluent to give the title compound (244 mg, 91%) as white solid, m.p. 122–123°C. 1H-NMR (500 MHz, in CDCl3 at 25°C): δ 9.09 (1 H, d, J = 9.1 Hz), 7.82 (1 H, s), 6.66 (1 H, d, J = 9.1 Hz), 3.87 (3 H, s), 3.84 (3 H, s), 3.80 (3 H, s), 1.55 (9 H, s). 13C-NMR (125 MHz, CDCl3): δ155.2, 152.2, 141.4, 124.2, 124.0, 118.1, 106.8, 70.4, 61.5, 60.8, 55.9, 28.3. Anal. Calcd for C14H21NO4: C, 62.90; H, 7.92; N, 5.24. Found: C, 63.04; H, 7.90; N 5.15. Crystals suitable for X-ray analysis were grown by slow solvent diffusion by layering hexane over a solution of the nitrone in dichloromethane.
H atoms atoms are treated by constrained refinement. The bond lengths of the hydrogen atoms to their parent atoms in six methyl groups are all equal to 0.96 Å while the others are equal to 0.93 Å.
Nitrones are versatile organic compounds widely used as 1,3-dipoles in cycloadditions,(Merino & Padwa, 2004; Torsell, 1988) spin trapping agents in free radical chemistry (Jasen, 1971; Usuki et al., 2006) and also in biological studies. (Zhang et al., 2000) Recently they have also been employed as therapeutics in age-related diseases. (Floyd, 2006) Nitrones undergo many reactions, such as the Behrend Rearrangement, nitrone-oxime O-ether rearrangement, and thermolytic alkene elimination. (Torsell, 1988) While the most conventional procedures for the preparation of nitrones have been the condensation of N-monosubstituted hydroxylamines with carbonyl compounds and the N-alkylation of oximes, (Torsell, 1988) a newly reported high yielding and chemoselective procedure for the conversion of imines to nitrones using catalytic amounts of methyltrioxorhenium represents a breakthrough in nitrone synthesis. (Soldaini et al., 2007) We have recently shown that nitrones derived from aromatic aldehydes can be used as convenient precursors to carbocyclic carbene ligands for the synthesis of novel and catalytically useful Pd compounds. (Yao et al., 2007) The formation of nitrone-based Pd complexes involves the selective C—H activation of the aromatic ring via orthopalladation directed by the oxygen atom on the nitrone moiety. It can be expected that the stereochemistry around the C=N of the nitrone group would have a pronounced effect in formation of the Ccarbene—Pd bond as we believe that the oxygen initially ligates the palladium species and directs the subsequent ortho-palladation. For this purpose, we have prepared the title compound and its structure analyzed by X-ray crystallography. The C7=N1 double bond leads to a plane containing C8, O1, N1, C7 and C6 which is not coplanar with the phenyl ring; the torsion angle N1 - C7 - C6 - C1 is -10.2 (3) °.
For related literature, see: Floyd (2006); Jasen (1971); Merino & Padwa (2004); Soldaini et al. (2007); Torsell (1988); Usuki et al. (2006); Yao et al. (2007); Zhang et al. (2000).
Data collection: SMART (Bruker, 1999); cell refinement: SMART and SAINT (Bruker, 1999); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997a); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997a); molecular graphics: SHELXTL (Sheldrick, 1997b); software used to prepare material for publication: SHELXTL.
C14H21NO4 | Z = 2 |
Mr = 267.32 | F(000) = 288 |
Triclinic, P1 | Dx = 1.214 Mg m−3 |
Hall symbol: -P 1 | Melting point = 395–396 K |
a = 8.7424 (15) Å | Mo Kα radiation, λ = 0.71073 Å |
b = 9.5039 (17) Å | Cell parameters from 427 reflections |
c = 9.8424 (17) Å | θ = −14–14° |
α = 74.055 (3)° | µ = 0.09 mm−1 |
β = 68.612 (3)° | T = 293 K |
γ = 82.108 (3)° | Plate, colorless |
V = 731.5 (2) Å3 | 0.50 × 0.40 × 0.40 mm |
Siemens SMART CCD PLATFORM diffractometer | 2563 independent reflections |
Radiation source: fine-focus sealed tube | 2189 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.017 |
Detector resolution: 0 pixels mm-1 | θmax = 25.0°, θmin = 2.2° |
ω scans | h = −10→10 |
Absorption correction: multi-scan (SADABS; Sheldrick, 2000) | k = −11→11 |
Tmin = 0.857, Tmax = 0.965 | l = −11→11 |
5580 measured reflections |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.042 | H-atom parameters constrained |
wR(F2) = 0.124 | w = 1/[σ2(Fo2) + (0.0678P)2 + 0.113P] where P = (Fo2 + 2Fc2)/3 |
S = 1.07 | (Δ/σ)max < 0.001 |
2563 reflections | Δρmax = 0.23 e Å−3 |
179 parameters | Δρmin = −0.17 e Å−3 |
0 restraints | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.024 (6) |
C14H21NO4 | γ = 82.108 (3)° |
Mr = 267.32 | V = 731.5 (2) Å3 |
Triclinic, P1 | Z = 2 |
a = 8.7424 (15) Å | Mo Kα radiation |
b = 9.5039 (17) Å | µ = 0.09 mm−1 |
c = 9.8424 (17) Å | T = 293 K |
α = 74.055 (3)° | 0.50 × 0.40 × 0.40 mm |
β = 68.612 (3)° |
Siemens SMART CCD PLATFORM diffractometer | 2563 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2000) | 2189 reflections with I > 2σ(I) |
Tmin = 0.857, Tmax = 0.965 | Rint = 0.017 |
5580 measured reflections |
R[F2 > 2σ(F2)] = 0.042 | 0 restraints |
wR(F2) = 0.124 | H-atom parameters constrained |
S = 1.07 | Δρmax = 0.23 e Å−3 |
2563 reflections | Δρmin = −0.17 e Å−3 |
179 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.75304 (15) | 1.17217 (13) | 0.34565 (15) | 0.0717 (4) | |
O2 | 1.29356 (14) | 0.62646 (12) | 0.30972 (13) | 0.0647 (3) | |
O3 | 1.09014 (13) | 0.54726 (11) | 0.20004 (11) | 0.0584 (3) | |
O4 | 0.82513 (12) | 0.72922 (12) | 0.16273 (12) | 0.0610 (3) | |
N1 | 0.70119 (15) | 1.11834 (13) | 0.26398 (14) | 0.0523 (3) | |
C1 | 1.00430 (18) | 0.94615 (16) | 0.31636 (17) | 0.0518 (4) | |
H1 | 0.9838 | 1.0337 | 0.3462 | 0.062* | |
C2 | 1.13649 (18) | 0.85577 (16) | 0.33577 (17) | 0.0532 (4) | |
H2 | 1.2046 | 0.8837 | 0.3767 | 0.064* | |
C3 | 1.16811 (17) | 0.72379 (16) | 0.29453 (16) | 0.0496 (4) | |
C4 | 1.06241 (17) | 0.68092 (15) | 0.23628 (15) | 0.0481 (3) | |
C5 | 0.93260 (17) | 0.77314 (16) | 0.21437 (15) | 0.0481 (3) | |
C6 | 0.90073 (17) | 0.90925 (16) | 0.25308 (16) | 0.0484 (3) | |
C7 | 0.76466 (18) | 0.99913 (17) | 0.22132 (17) | 0.0526 (4) | |
H7 | 0.7175 | 0.9683 | 0.1642 | 0.063* | |
C8 | 0.55423 (19) | 1.20292 (18) | 0.22727 (18) | 0.0600 (4) | |
C9 | 0.5125 (3) | 1.1466 (3) | 0.1152 (3) | 0.0883 (6) | |
H93 | 0.4750 | 1.0486 | 0.1604 | 0.132* | |
H92 | 0.6087 | 1.1466 | 0.0275 | 0.132* | |
H91 | 0.4275 | 1.2089 | 0.0867 | 0.132* | |
C10 | 0.4129 (2) | 1.1846 (3) | 0.3765 (2) | 0.0886 (6) | |
H103 | 0.3178 | 1.2403 | 0.3611 | 0.133* | |
H102 | 0.4435 | 1.2190 | 0.4457 | 0.133* | |
H101 | 0.3880 | 1.0830 | 0.4170 | 0.133* | |
C11 | 0.6005 (3) | 1.3618 (2) | 0.1600 (2) | 0.0835 (6) | |
H113 | 0.5067 | 1.4208 | 0.1458 | 0.125* | |
H112 | 0.6879 | 1.3701 | 0.0647 | 0.125* | |
H111 | 0.6363 | 1.3949 | 0.2268 | 0.125* | |
C12 | 1.4108 (2) | 0.6695 (2) | 0.3579 (3) | 0.0795 (6) | |
H123 | 1.4613 | 0.7567 | 0.2879 | 0.119* | |
H122 | 1.4935 | 0.5924 | 0.3627 | 0.119* | |
H121 | 1.3569 | 0.6883 | 0.4557 | 0.119* | |
C13 | 1.0042 (3) | 0.43237 (19) | 0.3183 (2) | 0.0809 (6) | |
H133 | 1.0439 | 0.4156 | 0.4007 | 0.121* | |
H132 | 1.0216 | 0.3447 | 0.2832 | 0.121* | |
H131 | 0.8889 | 0.4588 | 0.3514 | 0.121* | |
C14 | 0.8909 (2) | 0.7105 (2) | 0.0131 (2) | 0.0747 (5) | |
H143 | 0.9072 | 0.8047 | −0.0570 | 0.112* | |
H142 | 0.8155 | 0.6581 | −0.0035 | 0.112* | |
H141 | 0.9942 | 0.6561 | −0.0011 | 0.112* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0737 (8) | 0.0711 (7) | 0.0942 (9) | 0.0155 (6) | −0.0461 (7) | −0.0434 (7) |
O2 | 0.0582 (6) | 0.0675 (7) | 0.0777 (7) | 0.0129 (5) | −0.0316 (6) | −0.0285 (6) |
O3 | 0.0680 (7) | 0.0514 (6) | 0.0548 (6) | −0.0026 (5) | −0.0134 (5) | −0.0216 (5) |
O4 | 0.0507 (6) | 0.0757 (7) | 0.0690 (7) | −0.0063 (5) | −0.0217 (5) | −0.0342 (6) |
N1 | 0.0497 (7) | 0.0544 (7) | 0.0547 (7) | −0.0009 (5) | −0.0195 (5) | −0.0147 (6) |
C1 | 0.0526 (8) | 0.0492 (8) | 0.0589 (9) | −0.0023 (6) | −0.0211 (7) | −0.0187 (6) |
C2 | 0.0500 (8) | 0.0579 (9) | 0.0590 (9) | −0.0043 (6) | −0.0231 (7) | −0.0189 (7) |
C3 | 0.0447 (7) | 0.0540 (8) | 0.0479 (8) | −0.0008 (6) | −0.0134 (6) | −0.0130 (6) |
C4 | 0.0487 (8) | 0.0488 (8) | 0.0439 (7) | −0.0049 (6) | −0.0092 (6) | −0.0148 (6) |
C5 | 0.0438 (7) | 0.0551 (8) | 0.0465 (7) | −0.0091 (6) | −0.0117 (6) | −0.0161 (6) |
C6 | 0.0454 (7) | 0.0512 (8) | 0.0488 (8) | −0.0042 (6) | −0.0147 (6) | −0.0138 (6) |
C7 | 0.0502 (8) | 0.0571 (8) | 0.0563 (8) | −0.0015 (6) | −0.0213 (7) | −0.0189 (7) |
C8 | 0.0497 (8) | 0.0659 (10) | 0.0597 (9) | 0.0058 (7) | −0.0200 (7) | −0.0102 (7) |
C9 | 0.0826 (13) | 0.1032 (15) | 0.0964 (15) | 0.0171 (11) | −0.0562 (12) | −0.0270 (12) |
C10 | 0.0535 (10) | 0.1182 (17) | 0.0748 (12) | 0.0084 (10) | −0.0133 (9) | −0.0105 (11) |
C11 | 0.0779 (12) | 0.0673 (11) | 0.0897 (13) | 0.0123 (9) | −0.0241 (10) | −0.0081 (10) |
C12 | 0.0618 (10) | 0.0927 (13) | 0.1025 (14) | 0.0184 (9) | −0.0449 (10) | −0.0404 (11) |
C13 | 0.1072 (15) | 0.0552 (9) | 0.0737 (12) | −0.0161 (10) | −0.0179 (10) | −0.0171 (8) |
C14 | 0.0801 (12) | 0.0939 (13) | 0.0658 (11) | −0.0018 (10) | −0.0364 (9) | −0.0298 (10) |
O1—N1 | 1.2918 (16) | C8—C9 | 1.520 (3) |
O2—C3 | 1.3586 (18) | C8—C10 | 1.520 (2) |
O2—C12 | 1.421 (2) | C9—H93 | 0.9600 |
O3—C4 | 1.3788 (17) | C9—H92 | 0.9600 |
O3—C13 | 1.414 (2) | C9—H91 | 0.9600 |
O4—C5 | 1.3739 (16) | C10—H103 | 0.9600 |
O4—C14 | 1.425 (2) | C10—H102 | 0.9600 |
N1—C7 | 1.299 (2) | C10—H101 | 0.9600 |
N1—C8 | 1.5240 (19) | C11—H113 | 0.9600 |
C1—C2 | 1.381 (2) | C11—H112 | 0.9600 |
C1—C6 | 1.396 (2) | C11—H111 | 0.9600 |
C1—H1 | 0.9300 | C12—H123 | 0.9600 |
C2—C3 | 1.385 (2) | C12—H122 | 0.9600 |
C2—H2 | 0.9300 | C12—H121 | 0.9600 |
C3—C4 | 1.402 (2) | C13—H133 | 0.9600 |
C4—C5 | 1.380 (2) | C13—H132 | 0.9600 |
C5—C6 | 1.411 (2) | C13—H131 | 0.9600 |
C6—C7 | 1.445 (2) | C14—H143 | 0.9600 |
C7—H7 | 0.9300 | C14—H142 | 0.9600 |
C8—C11 | 1.518 (3) | C14—H141 | 0.9600 |
C3—O2—C12 | 117.46 (13) | H93—C9—H92 | 109.5 |
C4—O3—C13 | 113.76 (12) | C8—C9—H91 | 109.5 |
C5—O4—C14 | 116.22 (12) | H93—C9—H91 | 109.5 |
O1—N1—C7 | 122.97 (12) | H92—C9—H91 | 109.5 |
O1—N1—C8 | 114.34 (12) | C8—C10—H103 | 109.5 |
C7—N1—C8 | 122.64 (13) | C8—C10—H102 | 109.5 |
C2—C1—C6 | 121.58 (13) | H103—C10—H102 | 109.5 |
C2—C1—H1 | 119.2 | C8—C10—H101 | 109.5 |
C6—C1—H1 | 119.2 | H103—C10—H101 | 109.5 |
C1—C2—C3 | 120.34 (13) | H102—C10—H101 | 109.5 |
C1—C2—H2 | 119.8 | C8—C11—H113 | 109.5 |
C3—C2—H2 | 119.8 | C8—C11—H112 | 109.5 |
O2—C3—C2 | 125.16 (13) | H113—C11—H112 | 109.5 |
O2—C3—C4 | 115.39 (13) | C8—C11—H111 | 109.5 |
C2—C3—C4 | 119.42 (13) | H113—C11—H111 | 109.5 |
O3—C4—C5 | 120.53 (13) | H112—C11—H111 | 109.5 |
O3—C4—C3 | 119.60 (13) | O2—C12—H123 | 109.5 |
C5—C4—C3 | 119.87 (13) | O2—C12—H122 | 109.5 |
O4—C5—C4 | 120.03 (12) | H123—C12—H122 | 109.5 |
O4—C5—C6 | 118.53 (13) | O2—C12—H121 | 109.5 |
C4—C5—C6 | 121.32 (13) | H123—C12—H121 | 109.5 |
C1—C6—C5 | 117.41 (13) | H122—C12—H121 | 109.5 |
C1—C6—C7 | 125.82 (13) | O3—C13—H133 | 109.5 |
C5—C6—C7 | 116.77 (13) | O3—C13—H132 | 109.5 |
N1—C7—C6 | 126.98 (14) | H133—C13—H132 | 109.5 |
N1—C7—H7 | 116.5 | O3—C13—H131 | 109.5 |
C6—C7—H7 | 116.5 | H133—C13—H131 | 109.5 |
C11—C8—C9 | 109.38 (16) | H132—C13—H131 | 109.5 |
C11—C8—C10 | 111.50 (16) | O4—C14—H143 | 109.5 |
C9—C8—C10 | 111.30 (17) | O4—C14—H142 | 109.5 |
C11—C8—N1 | 106.89 (14) | H143—C14—H142 | 109.5 |
C9—C8—N1 | 111.94 (14) | O4—C14—H141 | 109.5 |
C10—C8—N1 | 105.73 (13) | H143—C14—H141 | 109.5 |
C8—C9—H93 | 109.5 | H142—C14—H141 | 109.5 |
C8—C9—H92 | 109.5 |
Experimental details
Crystal data | |
Chemical formula | C14H21NO4 |
Mr | 267.32 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 293 |
a, b, c (Å) | 8.7424 (15), 9.5039 (17), 9.8424 (17) |
α, β, γ (°) | 74.055 (3), 68.612 (3), 82.108 (3) |
V (Å3) | 731.5 (2) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.50 × 0.40 × 0.40 |
Data collection | |
Diffractometer | Siemens SMART CCD PLATFORM |
Absorption correction | Multi-scan (SADABS; Sheldrick, 2000) |
Tmin, Tmax | 0.857, 0.965 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 5580, 2563, 2189 |
Rint | 0.017 |
(sin θ/λ)max (Å−1) | 0.595 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.042, 0.124, 1.07 |
No. of reflections | 2563 |
No. of parameters | 179 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.23, −0.17 |
Computer programs: SMART (Bruker, 1999), SMART and SAINT (Bruker, 1999), SAINT, SHELXS97 (Sheldrick, 1997a), SHELXL97 (Sheldrick, 1997a), SHELXTL (Sheldrick, 1997b), SHELXTL.
Nitrones are versatile organic compounds widely used as 1,3-dipoles in cycloadditions,(Merino & Padwa, 2004; Torsell, 1988) spin trapping agents in free radical chemistry (Jasen, 1971; Usuki et al., 2006) and also in biological studies. (Zhang et al., 2000) Recently they have also been employed as therapeutics in age-related diseases. (Floyd, 2006) Nitrones undergo many reactions, such as the Behrend Rearrangement, nitrone-oxime O-ether rearrangement, and thermolytic alkene elimination. (Torsell, 1988) While the most conventional procedures for the preparation of nitrones have been the condensation of N-monosubstituted hydroxylamines with carbonyl compounds and the N-alkylation of oximes, (Torsell, 1988) a newly reported high yielding and chemoselective procedure for the conversion of imines to nitrones using catalytic amounts of methyltrioxorhenium represents a breakthrough in nitrone synthesis. (Soldaini et al., 2007) We have recently shown that nitrones derived from aromatic aldehydes can be used as convenient precursors to carbocyclic carbene ligands for the synthesis of novel and catalytically useful Pd compounds. (Yao et al., 2007) The formation of nitrone-based Pd complexes involves the selective C—H activation of the aromatic ring via orthopalladation directed by the oxygen atom on the nitrone moiety. It can be expected that the stereochemistry around the C=N of the nitrone group would have a pronounced effect in formation of the Ccarbene—Pd bond as we believe that the oxygen initially ligates the palladium species and directs the subsequent ortho-palladation. For this purpose, we have prepared the title compound and its structure analyzed by X-ray crystallography. The C7=N1 double bond leads to a plane containing C8, O1, N1, C7 and C6 which is not coplanar with the phenyl ring; the torsion angle N1 - C7 - C6 - C1 is -10.2 (3) °.