Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807027900/bg2064sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807027900/bg2064Isup2.hkl |
CCDC reference: 654980
Polystyrene-bound 1,3-butadiene-1-carboxylic acid (1.4 mmol/g, 600 mg) was treated with N-ethylmaleimide (8.4 mmol, 1.05 g) in toluene (1.0 ml) at room temperature for 48 h. Cleavage with TFA-CH2Cl2 1:4 (8 ml) over 2 h at room temperature and purification by successive trituration with hexane, Et2O and EtOAc gave the endo cycloadduct (75 mg, 40%) as white crystals, mp 156–158 °C.
The H atom connected to the carboxylate oxygen was situated from the difference map and refined isotropically. Other H atoms were introduced at calculated positions and allowed to ride, with C—H = 0.95–1.00 Å, Uiso=1.2/1.5× Ueq(carrier).
The Diels-Alder cycloaddition reactions between deactivated dienes and electron-deficient dienophiles are generally known to be thermodynamically disfavoured. We have recently found that when low solvent volumes (Morphy et al., 2002) were used for the reaction, the disfavoured cycloaddition of the 4-(bromomethyl)-phenoxymethyl polystyrene-bound (E)-1,3-butadiene-1-carboxylic acid with N-ethylmaleimide (PhMe, rt, 2 d) gave the endo cycloadduct in 40% yield (Kiriazis et al., 2004). The hexahydro-1,3-dioxoisoindole structure of the cycloadduct is very interesting in medicinal chemistry. For example, the related compounds are known to increase the blood platelet count in thrombocytopenia (Kanai et al., 2000) and to possess anticonvulsant activity (Bailleux et al., 1994).
For related literature, see: Bailleux et al. (1994); Kanai et al. (2000); Kiriazis et al. (2004); Morphy et al. (2002).
Data collection: COLLECT (Nonius, 2002); cell refinement: DIRAX (Duisenberg, 1992); data reduction: EVAL (Nonius, 2002); program(s) used to solve structure: SIR2002 (Burla et al., 2003); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Sheldrick, 1990); software used to prepare material for publication: SHELXTL.
C11H13NO4 | F(000) = 472 |
Mr = 223.22 | Dx = 1.431 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ybc | Cell parameters from 257 reflections |
a = 8.432 (1) Å | θ = 2.2–17.9° |
b = 8.588 (1) Å | µ = 0.11 mm−1 |
c = 14.342 (2) Å | T = 173 K |
β = 94.07 (2)° | Needle, colorless |
V = 1035.9 (2) Å3 | 0.25 × 0.11 × 0.10 mm |
Z = 4 |
Nonius Kappa CCD diffractometer | 2350 independent reflections |
Radiation source: fine-focus sealed tube | 1345 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.078 |
ω scans | θmax = 27.5°, θmin = 5.3° |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | h = −9→10 |
Tmin = 0.97, Tmax = 0.99 | k = −11→11 |
7378 measured reflections | l = −18→12 |
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)] = 0.056 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.130 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.00 | w = 1/[σ2(Fo2) + (0.0571P)2] where P = (Fo2 + 2Fc2)/3 |
2350 reflections | (Δ/σ)max < 0.001 |
149 parameters | Δρmax = 0.41 e Å−3 |
0 restraints | Δρmin = −0.25 e Å−3 |
C11H13NO4 | V = 1035.9 (2) Å3 |
Mr = 223.22 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 8.432 (1) Å | µ = 0.11 mm−1 |
b = 8.588 (1) Å | T = 173 K |
c = 14.342 (2) Å | 0.25 × 0.11 × 0.10 mm |
β = 94.07 (2)° |
Nonius Kappa CCD diffractometer | 2350 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | 1345 reflections with I > 2σ(I) |
Tmin = 0.97, Tmax = 0.99 | Rint = 0.078 |
7378 measured reflections |
R[F2 > 2σ(F2)] = 0.056 | 0 restraints |
wR(F2) = 0.130 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.00 | Δρmax = 0.41 e Å−3 |
2350 reflections | Δρmin = −0.25 e Å−3 |
149 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 | 1.20615 (19) | 0.12766 (19) | 0.18956 (12) | 0.0291 (5) | |
H1A | 1.305 (3) | 0.108 (3) | 0.2114 (19) | 0.040 (8)* | |
O2 | 1.20296 (19) | −0.1224 (2) | 0.14398 (13) | 0.0344 (5) | |
O3 | 1.01229 (17) | −0.02571 (19) | 0.33666 (12) | 0.0275 (4) | |
O4 | 0.48321 (17) | 0.0661 (2) | 0.28732 (12) | 0.0337 (5) | |
N1 | 0.74206 (19) | 0.0088 (2) | 0.33060 (13) | 0.0191 (5) | |
C1 | 1.1350 (3) | 0.0004 (3) | 0.15529 (17) | 0.0230 (6) | |
C2 | 0.9591 (2) | 0.0274 (3) | 0.12836 (17) | 0.0208 (5) | |
H2A | 0.9518 | 0.0958 | 0.0718 | 0.025* | |
C3 | 0.8682 (3) | −0.1201 (3) | 0.10316 (16) | 0.0244 (6) | |
H3A | 0.9225 | −0.2159 | 0.0965 | 0.029* | |
C4 | 0.7109 (3) | −0.1129 (3) | 0.09050 (17) | 0.0271 (6) | |
H4A | 0.6509 | −0.2048 | 0.0771 | 0.032* | |
C5 | 0.6282 (3) | 0.0415 (3) | 0.09743 (17) | 0.0272 (6) | |
H5A | 0.5127 | 0.0242 | 0.1009 | 0.033* | |
H5B | 0.6436 | 0.1039 | 0.0408 | 0.033* | |
C6 | 0.6941 (2) | 0.1316 (3) | 0.18465 (16) | 0.0208 (5) | |
H6A | 0.6670 | 0.2445 | 0.1772 | 0.025* | |
C7 | 0.8756 (2) | 0.1135 (3) | 0.20590 (15) | 0.0184 (5) | |
H7A | 0.9244 | 0.2190 | 0.2154 | 0.022* | |
C8 | 0.8919 (2) | 0.0247 (3) | 0.29702 (16) | 0.0187 (5) | |
C9 | 0.6239 (2) | 0.0690 (3) | 0.27090 (16) | 0.0216 (5) | |
C10 | 0.7154 (3) | −0.0611 (3) | 0.42150 (17) | 0.0251 (6) | |
H10A | 0.8034 | −0.1338 | 0.4396 | 0.030* | |
H10B | 0.6151 | −0.1214 | 0.4164 | 0.030* | |
C11 | 0.7061 (3) | 0.0629 (3) | 0.49656 (18) | 0.0313 (6) | |
H11A | 0.6884 | 0.0130 | 0.5564 | 0.047* | |
H11B | 0.6180 | 0.1340 | 0.4793 | 0.047* | |
H11C | 0.8061 | 0.1215 | 0.5024 | 0.047* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0200 (8) | 0.0271 (9) | 0.0400 (12) | −0.0019 (8) | 0.0004 (7) | 0.0025 (9) |
O2 | 0.0329 (9) | 0.0281 (10) | 0.0428 (12) | 0.0084 (8) | 0.0069 (8) | −0.0017 (9) |
O3 | 0.0229 (8) | 0.0337 (10) | 0.0256 (10) | 0.0041 (7) | −0.0020 (7) | 0.0018 (8) |
O4 | 0.0199 (8) | 0.0499 (12) | 0.0315 (11) | 0.0012 (8) | 0.0033 (7) | 0.0026 (9) |
N1 | 0.0222 (9) | 0.0199 (11) | 0.0154 (11) | −0.0004 (8) | 0.0033 (8) | 0.0012 (8) |
C1 | 0.0276 (12) | 0.0247 (13) | 0.0173 (13) | −0.0012 (11) | 0.0065 (10) | 0.0037 (11) |
C2 | 0.0249 (11) | 0.0215 (13) | 0.0165 (13) | 0.0021 (10) | 0.0035 (9) | 0.0024 (10) |
C3 | 0.0329 (13) | 0.0208 (12) | 0.0195 (14) | 0.0024 (11) | 0.0011 (10) | −0.0047 (11) |
C4 | 0.0347 (13) | 0.0241 (13) | 0.0221 (14) | −0.0067 (11) | 0.0004 (10) | −0.0058 (11) |
C5 | 0.0259 (12) | 0.0341 (15) | 0.0210 (14) | −0.0010 (11) | −0.0028 (10) | −0.0003 (12) |
C6 | 0.0215 (11) | 0.0191 (11) | 0.0214 (13) | 0.0027 (10) | −0.0017 (9) | −0.0013 (11) |
C7 | 0.0201 (11) | 0.0158 (11) | 0.0192 (13) | −0.0024 (9) | 0.0011 (9) | −0.0010 (10) |
C8 | 0.0203 (11) | 0.0162 (12) | 0.0191 (13) | 0.0006 (10) | −0.0013 (9) | −0.0054 (10) |
C9 | 0.0216 (11) | 0.0220 (13) | 0.0209 (14) | 0.0018 (10) | −0.0006 (10) | −0.0041 (11) |
C10 | 0.0307 (12) | 0.0260 (13) | 0.0193 (14) | 0.0005 (11) | 0.0057 (10) | 0.0025 (11) |
C11 | 0.0345 (13) | 0.0380 (15) | 0.0215 (15) | −0.0024 (12) | 0.0020 (11) | −0.0011 (12) |
O1—C1 | 1.325 (3) | C4—H4A | 0.9500 |
O1—H1A | 0.89 (3) | C5—C6 | 1.541 (3) |
O2—C1 | 1.217 (3) | C5—H5A | 0.9900 |
O3—C8 | 1.208 (3) | C5—H5B | 0.9900 |
O4—C9 | 1.226 (2) | C6—C9 | 1.508 (3) |
N1—C9 | 1.368 (3) | C6—C7 | 1.547 (3) |
N1—C8 | 1.391 (3) | C6—H6A | 1.0000 |
N1—C10 | 1.467 (3) | C7—C8 | 1.511 (3) |
C1—C2 | 1.523 (3) | C7—H7A | 1.0000 |
C2—C3 | 1.511 (3) | C10—C11 | 1.520 (3) |
C2—C7 | 1.546 (3) | C10—H10A | 0.9900 |
C2—H2A | 1.0000 | C10—H10B | 0.9900 |
C3—C4 | 1.327 (3) | C11—H11A | 0.9800 |
C3—H3A | 0.9500 | C11—H11B | 0.9800 |
C4—C5 | 1.505 (3) | C11—H11C | 0.9800 |
C1—O1—H1A | 111.1 (18) | C9—C6—H6A | 109.5 |
C9—N1—C8 | 112.67 (19) | C5—C6—H6A | 109.5 |
C9—N1—C10 | 124.08 (17) | C7—C6—H6A | 109.5 |
C8—N1—C10 | 123.24 (18) | C8—C7—C2 | 111.26 (18) |
O2—C1—O1 | 124.0 (2) | C8—C7—C6 | 104.42 (17) |
O2—C1—C2 | 123.9 (2) | C2—C7—C6 | 113.64 (18) |
O1—C1—C2 | 112.1 (2) | C8—C7—H7A | 109.1 |
C3—C2—C1 | 113.65 (19) | C2—C7—H7A | 109.1 |
C3—C2—C7 | 108.91 (17) | C6—C7—H7A | 109.1 |
C1—C2—C7 | 112.04 (18) | O3—C8—N1 | 123.7 (2) |
C3—C2—H2A | 107.3 | O3—C8—C7 | 127.59 (19) |
C1—C2—H2A | 107.3 | N1—C8—C7 | 108.66 (18) |
C7—C2—H2A | 107.3 | O4—C9—N1 | 122.9 (2) |
C4—C3—C2 | 118.6 (2) | O4—C9—C6 | 127.3 (2) |
C4—C3—H3A | 120.7 | N1—C9—C6 | 109.74 (17) |
C2—C3—H3A | 120.7 | N1—C10—C11 | 111.22 (19) |
C3—C4—C5 | 119.7 (2) | N1—C10—H10A | 109.4 |
C3—C4—H4A | 120.2 | C11—C10—H10A | 109.4 |
C5—C4—H4A | 120.2 | N1—C10—H10B | 109.4 |
C4—C5—C6 | 110.73 (19) | C11—C10—H10B | 109.4 |
C4—C5—H5A | 109.5 | H10A—C10—H10B | 108.0 |
C6—C5—H5A | 109.5 | C10—C11—H11A | 109.5 |
C4—C5—H5B | 109.5 | C10—C11—H11B | 109.5 |
C6—C5—H5B | 109.5 | H11A—C11—H11B | 109.5 |
H5A—C5—H5B | 108.1 | C10—C11—H11C | 109.5 |
C9—C6—C5 | 110.30 (18) | H11A—C11—H11C | 109.5 |
C9—C6—C7 | 104.05 (18) | H11B—C11—H11C | 109.5 |
C5—C6—C7 | 113.84 (17) | ||
O2—C1—C2—C3 | 11.0 (3) | C9—N1—C8—O3 | −176.9 (2) |
O1—C1—C2—C3 | −171.04 (19) | C10—N1—C8—O3 | 4.7 (3) |
O2—C1—C2—C7 | 135.0 (2) | C9—N1—C8—C7 | 3.2 (3) |
O1—C1—C2—C7 | −47.1 (2) | C10—N1—C8—C7 | −175.14 (19) |
C1—C2—C3—C4 | 171.3 (2) | C2—C7—C8—O3 | 51.0 (3) |
C7—C2—C3—C4 | 45.7 (3) | C6—C7—C8—O3 | 174.0 (2) |
C2—C3—C4—C5 | 2.6 (3) | C2—C7—C8—N1 | −129.13 (18) |
C3—C4—C5—C6 | −46.2 (3) | C6—C7—C8—N1 | −6.2 (2) |
C4—C5—C6—C9 | −78.7 (2) | C8—N1—C9—O4 | 179.7 (2) |
C4—C5—C6—C7 | 37.8 (3) | C10—N1—C9—O4 | −2.0 (3) |
C3—C2—C7—C8 | 68.7 (2) | C8—N1—C9—C6 | 1.3 (3) |
C1—C2—C7—C8 | −57.9 (2) | C10—N1—C9—C6 | 179.67 (19) |
C3—C2—C7—C6 | −48.8 (2) | C5—C6—C9—O4 | −60.9 (3) |
C1—C2—C7—C6 | −175.39 (19) | C7—C6—C9—O4 | 176.6 (2) |
C9—C6—C7—C8 | 6.6 (2) | C5—C6—C9—N1 | 117.4 (2) |
C5—C6—C7—C8 | −113.5 (2) | C7—C6—C9—N1 | −5.1 (2) |
C9—C6—C7—C2 | 128.0 (2) | C9—N1—C10—C11 | −82.9 (3) |
C5—C6—C7—C2 | 7.9 (3) | C8—N1—C10—C11 | 95.3 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1A···O4i | 0.89 (3) | 1.83 (3) | 2.690 (2) | 164 (2) |
Symmetry code: (i) x+1, y, z. |
Experimental details
Crystal data | |
Chemical formula | C11H13NO4 |
Mr | 223.22 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 173 |
a, b, c (Å) | 8.432 (1), 8.588 (1), 14.342 (2) |
β (°) | 94.07 (2) |
V (Å3) | 1035.9 (2) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.11 |
Crystal size (mm) | 0.25 × 0.11 × 0.10 |
Data collection | |
Diffractometer | Nonius Kappa CCD |
Absorption correction | Multi-scan (SADABS; Sheldrick, 1996) |
Tmin, Tmax | 0.97, 0.99 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 7378, 2350, 1345 |
Rint | 0.078 |
(sin θ/λ)max (Å−1) | 0.650 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.056, 0.130, 1.00 |
No. of reflections | 2350 |
No. of parameters | 149 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.41, −0.25 |
Computer programs: COLLECT (Nonius, 2002), DIRAX (Duisenberg, 1992), EVAL (Nonius, 2002), SIR2002 (Burla et al., 2003), SHELXL97 (Sheldrick, 1997), SHELXTL (Sheldrick, 1990), SHELXTL.
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1A···O4i | 0.89 (3) | 1.83 (3) | 2.690 (2) | 164 (2) |
Symmetry code: (i) x+1, y, z. |
The Diels-Alder cycloaddition reactions between deactivated dienes and electron-deficient dienophiles are generally known to be thermodynamically disfavoured. We have recently found that when low solvent volumes (Morphy et al., 2002) were used for the reaction, the disfavoured cycloaddition of the 4-(bromomethyl)-phenoxymethyl polystyrene-bound (E)-1,3-butadiene-1-carboxylic acid with N-ethylmaleimide (PhMe, rt, 2 d) gave the endo cycloadduct in 40% yield (Kiriazis et al., 2004). The hexahydro-1,3-dioxoisoindole structure of the cycloadduct is very interesting in medicinal chemistry. For example, the related compounds are known to increase the blood platelet count in thrombocytopenia (Kanai et al., 2000) and to possess anticonvulsant activity (Bailleux et al., 1994).