
Supporting information
![]() | Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536805042169/su6261sup1.cif |
![]() | Structure factor file (CIF format) https://doi.org/10.1107/S1600536805042169/su62613asup2.hkl |
CCDC reference: 296683
3-Methylenephthalide, (1), and C,N-diphenylnitrone, (2), were synthesized according to the literature procedures (Liu & Uwe or Liu & Howe, 1983; Brüning et al., 1973). A solution of (2) (1.97 g, 10 mmol), (1) (1.46 g, 10 mmol) and hydroquinone (0.05 g) in ethylacetate (40 ml) was stirred and refluxed for 24 h under an atmosphere of nitrogen. The solvent was then evaporated under reduced pressure. The residue was crystallized in ethanol, leading to a mixture of diastereoisomers (3a) and (3b). They were separated and purified by chromatography on silica gel (eluant chloroform/hexane/ether 50:45:5). The spirocompounds (3a) and (3b) were finally recrystallized from ethanol.
All H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms with C—H distances equal to 0.95–1.00 Å and Uiso(H) = 1.2Ueq(C). Please check changes to text.
Data collection: CrysAlis CCD (Oxford Diffraction, 2003); cell refinement: CrysAlis RED (Oxford Diffraction, 2003); data reduction: CrysAlis RED; program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).
![]() | Fig. 1. The molecular structure of (3a), showing the atom-labelling scheme and displacement ellipsoids drawn at the 30% probability level. |
C22H17NO3 | F(000) = 720 |
Mr = 343.37 | Dx = 1.337 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2yn | Cell parameters from 3224 reflections |
a = 5.1476 (6) Å | θ = 3.1–28.3° |
b = 15.3139 (18) Å | µ = 0.09 mm−1 |
c = 21.653 (3) Å | T = 180 K |
β = 91.365 (10)° | Block, colorless |
V = 1706.4 (4) Å3 | 0.51 × 0.37 × 0.35 mm |
Z = 4 |
Oxford Diffraction XCALIBUR diffractometer | 4219 independent reflections |
Radiation source: fine-focus sealed tube | 2777 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.067 |
ω–ϕ scans | θmax = 28.3°, θmin = 3.1° |
Absorption correction: multi-scan (Blessing, 1995) | h = −6→6 |
Tmin = 0.932, Tmax = 0.967 | k = −20→19 |
13897 measured reflections | l = −28→27 |
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)] = 0.048 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.127 | H-atom parameters constrained |
S = 0.93 | w = 1/[σ2(Fo2) + (0.0717P)2] where P = (Fo2 + 2Fc2)/3 |
4219 reflections | (Δ/σ)max < 0.001 |
235 parameters | Δρmax = 0.21 e Å−3 |
0 restraints | Δρmin = −0.22 e Å−3 |
C22H17NO3 | V = 1706.4 (4) Å3 |
Mr = 343.37 | Z = 4 |
Monoclinic, P21/n | Mo Kα radiation |
a = 5.1476 (6) Å | µ = 0.09 mm−1 |
b = 15.3139 (18) Å | T = 180 K |
c = 21.653 (3) Å | 0.51 × 0.37 × 0.35 mm |
β = 91.365 (10)° |
Oxford Diffraction XCALIBUR diffractometer | 4219 independent reflections |
Absorption correction: multi-scan (Blessing, 1995) | 2777 reflections with I > 2σ(I) |
Tmin = 0.932, Tmax = 0.967 | Rint = 0.067 |
13897 measured reflections |
R[F2 > 2σ(F2)] = 0.048 | 0 restraints |
wR(F2) = 0.127 | H-atom parameters constrained |
S = 0.93 | Δρmax = 0.21 e Å−3 |
4219 reflections | Δρmin = −0.22 e Å−3 |
235 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 | ||
C1 | 0.1354 (3) | 0.26085 (9) | 0.07689 (6) | 0.0272 (3) | |
C2 | 0.0393 (3) | 0.30234 (9) | 0.13496 (6) | 0.0272 (3) | |
C3 | −0.1528 (3) | 0.36359 (10) | 0.14395 (7) | 0.0349 (4) | |
H3 | −0.2474 | 0.3884 | 0.1101 | 0.042* | |
C4 | −0.2027 (3) | 0.38754 (11) | 0.20446 (7) | 0.0383 (4) | |
H4 | −0.3343 | 0.4295 | 0.2119 | 0.046* | |
C5 | −0.0655 (3) | 0.35187 (11) | 0.25406 (7) | 0.0382 (4) | |
H5 | −0.1052 | 0.3692 | 0.2949 | 0.046* | |
C6 | 0.1272 (3) | 0.29168 (11) | 0.24486 (6) | 0.0364 (4) | |
H6 | 0.2243 | 0.2677 | 0.2786 | 0.044* | |
C7 | 0.1752 (3) | 0.26721 (9) | 0.18465 (6) | 0.0291 (3) | |
C8 | 0.3625 (3) | 0.20312 (10) | 0.16154 (7) | 0.0347 (3) | |
C11 | −0.0587 (3) | 0.21464 (11) | 0.03401 (6) | 0.0342 (3) | |
H11A | −0.2354 | 0.2390 | 0.0385 | 0.041* | |
H11B | −0.0633 | 0.1512 | 0.0428 | 0.041* | |
C12 | 0.0429 (3) | 0.23208 (9) | −0.03141 (6) | 0.0275 (3) | |
H12 | −0.0793 | 0.2718 | −0.0544 | 0.033* | |
C111 | 0.3874 (3) | 0.33815 (9) | −0.06237 (6) | 0.0273 (3) | |
C112 | 0.5636 (3) | 0.40230 (10) | −0.04347 (7) | 0.0342 (3) | |
H112 | 0.6023 | 0.4104 | −0.0007 | 0.041* | |
C113 | 0.6825 (3) | 0.45418 (10) | −0.08675 (8) | 0.0414 (4) | |
H113 | 0.8028 | 0.4977 | −0.0735 | 0.050* | |
C114 | 0.6279 (3) | 0.44331 (11) | −0.14907 (8) | 0.0457 (4) | |
H114 | 0.7147 | 0.4776 | −0.1787 | 0.055* | |
C115 | 0.4469 (4) | 0.38237 (12) | −0.16760 (7) | 0.0472 (4) | |
H115 | 0.4038 | 0.3763 | −0.2103 | 0.057* | |
C116 | 0.3259 (3) | 0.32945 (10) | −0.12489 (7) | 0.0376 (4) | |
H116 | 0.2014 | 0.2874 | −0.1384 | 0.045* | |
C121 | 0.0813 (3) | 0.14899 (9) | −0.06793 (6) | 0.0257 (3) | |
C122 | −0.1008 (3) | 0.12601 (10) | −0.11306 (6) | 0.0307 (3) | |
H122 | −0.2418 | 0.1642 | −0.1224 | 0.037* | |
C123 | −0.0796 (3) | 0.04775 (10) | −0.14489 (7) | 0.0373 (4) | |
H123 | −0.2059 | 0.0326 | −0.1758 | 0.045* | |
C124 | 0.1243 (3) | −0.00802 (10) | −0.13176 (7) | 0.0379 (4) | |
H124 | 0.1387 | −0.0617 | −0.1534 | 0.045* | |
C125 | 0.3073 (3) | 0.01452 (10) | −0.08701 (7) | 0.0393 (4) | |
H125 | 0.4492 | −0.0235 | −0.0783 | 0.047* | |
C126 | 0.2859 (3) | 0.09213 (10) | −0.05472 (7) | 0.0337 (3) | |
H126 | 0.4112 | 0.1066 | −0.0235 | 0.040* | |
N1 | 0.2925 (2) | 0.27746 (8) | −0.01877 (5) | 0.0270 (3) | |
O1 | 0.25479 (18) | 0.32378 (6) | 0.04003 (4) | 0.0299 (2) | |
O9 | 0.33314 (19) | 0.19889 (7) | 0.09869 (4) | 0.0326 (3) | |
O81 | 0.5164 (2) | 0.15885 (9) | 0.18940 (5) | 0.0554 (4) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0276 (7) | 0.0275 (7) | 0.0266 (7) | 0.0022 (6) | 0.0034 (5) | 0.0012 (5) |
C2 | 0.0277 (7) | 0.0282 (8) | 0.0259 (7) | −0.0019 (6) | 0.0019 (5) | −0.0017 (6) |
C3 | 0.0349 (8) | 0.0383 (9) | 0.0314 (8) | 0.0068 (7) | 0.0011 (6) | 0.0021 (6) |
C4 | 0.0368 (8) | 0.0393 (9) | 0.0391 (9) | 0.0092 (7) | 0.0049 (7) | −0.0057 (7) |
C5 | 0.0397 (8) | 0.0461 (10) | 0.0290 (8) | 0.0018 (7) | 0.0035 (6) | −0.0087 (7) |
C6 | 0.0394 (8) | 0.0441 (9) | 0.0257 (7) | 0.0044 (7) | −0.0019 (6) | −0.0022 (6) |
C7 | 0.0302 (7) | 0.0302 (8) | 0.0268 (7) | 0.0007 (6) | 0.0009 (6) | −0.0011 (6) |
C8 | 0.0367 (8) | 0.0357 (9) | 0.0317 (8) | 0.0053 (7) | 0.0010 (6) | −0.0006 (6) |
C11 | 0.0315 (8) | 0.0434 (9) | 0.0280 (8) | −0.0067 (7) | 0.0037 (6) | −0.0040 (6) |
C12 | 0.0258 (7) | 0.0314 (8) | 0.0252 (7) | 0.0025 (6) | −0.0004 (5) | −0.0004 (6) |
C111 | 0.0308 (7) | 0.0233 (7) | 0.0281 (7) | 0.0053 (6) | 0.0058 (6) | 0.0024 (5) |
C112 | 0.0374 (8) | 0.0294 (8) | 0.0359 (8) | −0.0001 (6) | 0.0033 (6) | 0.0037 (6) |
C113 | 0.0435 (9) | 0.0293 (8) | 0.0517 (10) | −0.0002 (7) | 0.0082 (7) | 0.0087 (7) |
C114 | 0.0568 (11) | 0.0339 (9) | 0.0471 (10) | 0.0035 (8) | 0.0177 (8) | 0.0139 (7) |
C115 | 0.0705 (12) | 0.0411 (10) | 0.0305 (8) | 0.0032 (9) | 0.0081 (8) | 0.0070 (7) |
C116 | 0.0510 (9) | 0.0330 (9) | 0.0288 (8) | −0.0015 (7) | 0.0019 (7) | 0.0028 (6) |
C121 | 0.0282 (7) | 0.0251 (7) | 0.0240 (7) | 0.0014 (6) | 0.0035 (5) | 0.0031 (5) |
C122 | 0.0313 (7) | 0.0319 (8) | 0.0288 (7) | 0.0043 (6) | −0.0010 (6) | −0.0005 (6) |
C123 | 0.0398 (9) | 0.0365 (9) | 0.0356 (8) | −0.0021 (7) | 0.0001 (7) | −0.0060 (7) |
C124 | 0.0455 (9) | 0.0251 (8) | 0.0437 (9) | −0.0014 (7) | 0.0127 (7) | −0.0016 (6) |
C125 | 0.0394 (8) | 0.0286 (8) | 0.0499 (9) | 0.0094 (7) | 0.0054 (7) | 0.0046 (7) |
C126 | 0.0321 (8) | 0.0317 (8) | 0.0371 (8) | 0.0035 (6) | −0.0035 (6) | 0.0039 (6) |
N1 | 0.0320 (6) | 0.0287 (6) | 0.0203 (6) | −0.0020 (5) | 0.0033 (5) | −0.0028 (5) |
O1 | 0.0373 (5) | 0.0295 (6) | 0.0230 (5) | −0.0033 (4) | 0.0054 (4) | −0.0034 (4) |
O9 | 0.0358 (6) | 0.0342 (6) | 0.0279 (5) | 0.0073 (5) | 0.0038 (4) | −0.0015 (4) |
O81 | 0.0616 (8) | 0.0626 (9) | 0.0418 (7) | 0.0327 (7) | −0.0047 (6) | 0.0033 (6) |
C1—O1 | 1.4026 (16) | C111—C112 | 1.392 (2) |
C1—O9 | 1.4617 (16) | C111—N1 | 1.4195 (17) |
C1—C2 | 1.5030 (18) | C112—C113 | 1.382 (2) |
C1—C11 | 1.5222 (19) | C112—H112 | 0.9500 |
C2—C7 | 1.3787 (19) | C113—C114 | 1.382 (2) |
C2—C3 | 1.380 (2) | C113—H113 | 0.9500 |
C3—C4 | 1.391 (2) | C114—C115 | 1.372 (2) |
C3—H3 | 0.9500 | C114—H114 | 0.9500 |
C4—C5 | 1.384 (2) | C115—C116 | 1.388 (2) |
C4—H4 | 0.9500 | C115—H115 | 0.9500 |
C5—C6 | 1.372 (2) | C116—H116 | 0.9500 |
C5—H5 | 0.9500 | C121—C122 | 1.3835 (19) |
C6—C7 | 1.3844 (19) | C121—C126 | 1.3908 (19) |
C6—H6 | 0.9500 | C122—C123 | 1.388 (2) |
C7—C8 | 1.472 (2) | C122—H122 | 0.9500 |
C8—O81 | 1.1951 (18) | C123—C124 | 1.378 (2) |
C8—O9 | 1.3671 (17) | C123—H123 | 0.9500 |
C11—C12 | 1.5450 (18) | C124—C125 | 1.379 (2) |
C11—H11A | 0.9900 | C124—H124 | 0.9500 |
C11—H11B | 0.9900 | C125—C126 | 1.385 (2) |
C12—N1 | 1.4805 (17) | C125—H125 | 0.9500 |
C12—C121 | 1.5134 (19) | C126—H126 | 0.9500 |
C12—H12 | 1.0000 | N1—O1 | 1.4743 (13) |
C111—C116 | 1.3892 (19) | ||
O1—C1—O9 | 108.57 (10) | C116—C111—N1 | 120.76 (13) |
O1—C1—C2 | 110.07 (11) | C112—C111—N1 | 119.91 (12) |
O9—C1—C2 | 104.17 (10) | C113—C112—C111 | 120.14 (14) |
O1—C1—C11 | 105.21 (11) | C113—C112—H112 | 119.9 |
O9—C1—C11 | 109.71 (12) | C111—C112—H112 | 119.9 |
C2—C1—C11 | 118.86 (11) | C114—C113—C112 | 120.65 (16) |
C7—C2—C3 | 120.48 (13) | C114—C113—H113 | 119.7 |
C7—C2—C1 | 108.48 (12) | C112—C113—H113 | 119.7 |
C3—C2—C1 | 131.03 (13) | C115—C114—C113 | 119.23 (15) |
C2—C3—C4 | 117.46 (14) | C115—C114—H114 | 120.4 |
C2—C3—H3 | 121.3 | C113—C114—H114 | 120.4 |
C4—C3—H3 | 121.3 | C114—C115—C116 | 120.97 (15) |
C5—C4—C3 | 121.67 (14) | C114—C115—H115 | 119.5 |
C5—C4—H4 | 119.2 | C116—C115—H115 | 119.5 |
C3—C4—H4 | 119.2 | C115—C116—C111 | 119.86 (15) |
C6—C5—C4 | 120.65 (14) | C115—C116—H116 | 120.1 |
C6—C5—H5 | 119.7 | C111—C116—H116 | 120.1 |
C4—C5—H5 | 119.7 | C122—C121—C126 | 118.88 (13) |
C5—C6—C7 | 117.68 (13) | C122—C121—C12 | 119.23 (12) |
C5—C6—H6 | 121.2 | C126—C121—C12 | 121.77 (12) |
C7—C6—H6 | 121.2 | C121—C122—C123 | 120.69 (13) |
C2—C7—C6 | 122.05 (13) | C121—C122—H122 | 119.7 |
C2—C7—C8 | 108.61 (12) | C123—C122—H122 | 119.7 |
C6—C7—C8 | 129.34 (13) | C124—C123—C122 | 120.08 (14) |
O81—C8—O9 | 122.13 (14) | C124—C123—H123 | 120.0 |
O81—C8—C7 | 129.66 (14) | C122—C123—H123 | 120.0 |
O9—C8—C7 | 108.20 (12) | C123—C124—C125 | 119.61 (14) |
C1—C11—C12 | 104.32 (11) | C123—C124—H124 | 120.2 |
C1—C11—H11A | 110.9 | C125—C124—H124 | 120.2 |
C12—C11—H11A | 110.9 | C124—C125—C126 | 120.56 (14) |
C1—C11—H11B | 110.9 | C124—C125—H125 | 119.7 |
C12—C11—H11B | 110.9 | C126—C125—H125 | 119.7 |
H11A—C11—H11B | 108.9 | C125—C126—C121 | 120.17 (14) |
N1—C12—C121 | 111.58 (11) | C125—C126—H126 | 119.9 |
N1—C12—C11 | 102.89 (10) | C121—C126—H126 | 119.9 |
C121—C12—C11 | 112.64 (12) | C111—N1—O1 | 108.28 (10) |
N1—C12—H12 | 109.8 | C111—N1—C12 | 119.67 (11) |
C121—C12—H12 | 109.8 | O1—N1—C12 | 104.71 (9) |
C11—C12—H12 | 109.8 | C1—O1—N1 | 103.26 (9) |
C116—C111—C112 | 119.05 (13) | C8—O9—C1 | 110.50 (10) |
Experimental details
Crystal data | |
Chemical formula | C22H17NO3 |
Mr | 343.37 |
Crystal system, space group | Monoclinic, P21/n |
Temperature (K) | 180 |
a, b, c (Å) | 5.1476 (6), 15.3139 (18), 21.653 (3) |
β (°) | 91.365 (10) |
V (Å3) | 1706.4 (4) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.51 × 0.37 × 0.35 |
Data collection | |
Diffractometer | Oxford Diffraction XCALIBUR diffractometer |
Absorption correction | Multi-scan (Blessing, 1995) |
Tmin, Tmax | 0.932, 0.967 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 13897, 4219, 2777 |
Rint | 0.067 |
(sin θ/λ)max (Å−1) | 0.666 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.048, 0.127, 0.93 |
No. of reflections | 4219 |
No. of parameters | 235 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.21, −0.22 |
Computer programs: CrysAlis CCD (Oxford Diffraction, 2003), CrysAlis RED (Oxford Diffraction, 2003), CrysAlis RED, SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 1997), ORTEP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999).
The 1,3-dipolar cycloaddition reactions between nitrones (1,3-dipoles) and alkenes (dipolarophiles) is an extremely powerful synthetic method for the synthesis of the isoxazolidine ring system (Tufariello, 1984; Confalone & Huie, 1988; Torssell, 1988; Carruthers, 1990; Grünanger & Vita-Finzi, 1991; Frederickson, 1997). Best regarded as a concerted but asynchronous [3 + 2] suprafacial process, the reaction enables the creation of up to two new carbon stereocenters in a single step. In such a case, the [3 + 2]-addition could provide two pairs of regioisomeric (i.e. resulting from different addition senses) and diastereoisomeric (i.e. resulting from the endo or the exo addition) products via four possible transition states, as depicted in the scheme below.
[scheme1]
As part of our research on bicyclic spirocompounds (Fihi et al., 1995), we previously reported that the 1,3-dipolar cycloaddition of aromatic nitrile oxides with 3-methylenephthalide, (1), produced 3'-arylspiro[isobensofuran-1(3H),5'(4'H)isoxazol]-3-ones, (3), which possess good herbicidal and plant growth regulant activities (Howe & Liu, 1981). Recently, we reported the [3 + 2]-cycloaddition of methylene-γ-butyrolactones with several nitrones (Roussel et al., 2003). The reaction is highly regioselective and leads to a mixture of two diastereoisomers, the ratios of which were evaluated by 1H NMR (performed on the crude reaction mixture). The structures of the spiroadducts, (3a) and (3b), were elucidated only by 1H and 13C NMR. Our structural proposition was based on comparision with the spectroscopic data of similar adducts for which the structures are already established (Roussel et al., 2003; Cacciarini et al., 2000).
To confirm unambigously the structure assignments of (3a) and (3b), and to establish the absolute stereochemistry of each spiroheterocycle, a single-crystal X-ray study was carried out on the major spirocompound, (3a). As shown in Fig. 1, the stereochemistry of (3a) follows from the endo C═O approach, which favors the maximum of π electrons in the same space region. The molecule is built up from isobenzofuran-2-one and diphenyloxazoline groups linked by the spiro atom C1. The isobenzofuran fragment is planar, the largest deviation being −0.0295 (0) Å for atom O9, and the ketone atom, O81, lies in this plane. The oxazoline moiety has a half-chair conformation with atom O1 lying above the C1/C11/C12/N1 mean plane by 0.603 (2) Å. The isobenzofuran and oxazoline groups make a dihedral angle of 72.95 (4)°. The two phenyl rings, C111–C116 and C121–C126, attached to the oxazoline, are twisted with respect to the C1/C11/C12/N1 mean plane by 19.80 (9) and 80.21 (5)°, respectively. They are inclined to one another by 80.95 (4)°. The bond lengths and angles within the whole molecule are comparable to values found for related compounds (Cambridge Structural Database, Version 5.26; Allen, 2002).