organic compounds
Methyl 4-methyl-2-oxo-3,4-dihydrodibenzo[b,d]furan-4a(2H)-carboxylate
aCatalytic Hydrogenation Research Center, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China
*Correspondence e-mail: wangyifeng@zjut.edu.cn
The title compound, C15H14O4, has structural similarities to the alkaloid galanthamine, used in the treatment of Alzheimer's disease. The structure consists of a fused three-ring system comprising benzene and cyclohexenone fused to a central furan ring. The furan ring exhibits an with the carboxylate-substituted C atom as the flap, deviating by 0.352 (3) Å from the mean plane of other four furan-ring atoms. The cyclohexenone ring also exhibits an with the methyl-substituted C atom as the flap. The methyl and carboxylate groups are on opposite side of the plane of the other five atoms of the cyclohexenone ring. In the crystal, other than van der Waals contacts, there are weak intermolecular C—H⋯O interactions present linking the molecules to form a one-dimensional zigzag chain along the b-axis direction.
Keywords: crystal structure; hydrogen bonding; galanthamine.
CCDC reference: 1524459
Structure description
The title compound has a similar structural framework to that of galanthamine, an alkaloid used in the treatment of Alzheimer's disease, originally extracted from the Caucasian Snowdrop (Galanthus woronowii). It can be readily synthesized by Robinson of the Michael adduct of methyl 3-oxo-2,3-dihydrobenzofuran-2-carboxylate and (E)-pent-3-en-2-one. For background information and synthesis details, see: Bergonzini & Melchiorre (2012); Marco-Contelles et al. (2006); Yamanaka et al. (2012).
The molecular structure of the title compound (Fig. 1) has a fused three-ring system comprising benzene and cyclohexenone fused to a central furan. The furan ring exhibits an with atom C5 as the flap, which deviates by 0.352 (3) Å from the mean plane of other four atoms. This mean plane makes a dihedral angle of 22.80 (3)° with the plane of atoms O2/C5/C6. The cyclohexenone ring also exhibits an in which atom C4 acts as the flap, deviating from the mean plane of other five atoms of the cyclohexenone ring by 0.597 (2) Å, and this mean plane makes a dihedral angle of 42.64 (3)° with the plane of atoms C3/C4/C5. Atoms C13 of the methyl group and C14 of the carboxylate group are displaced from the mean plane of the other five atoms by 0.465 (2) and −1.483 (2) Å, respectively.
In the crystal, there are weak intermolecular C—H⋯O interactions present linking the molecules to form a one-dimensional zigzag chain along the b-axis direction (Table 1 and Fig. 2).
Synthesis and crystallization
Cu(OTf)2 (0.02 mmol, 7.2 mg, 10 mol%) and the ligand bis{2-[(4S,5S)-4,5-diphenyl-4,5-dihydrooxazol-2-yl]phenyl}amine (10 mol%) were dissolved in toluene (4 ml) at ambient temperature. Methyl 3-oxo-2,3-dihydrobenzofuran-2-carboxylate (0.2 mmol, 38.4 mg) was added and the mixture stirred for 10 minutes, followed by the addition of (E)-pent-3-en-2-one (0.22 mmol, 18.5 mg, 1.1 equiv.). The resulting mixture was stirred for 24 h at ambient temperature. After completion of the reaction, the solvent was evaporated under reduced pressure. The resulting crude mixture was purified by flash (ethyl acetate/hexane) on silica gel, and the Michael adduct methyl 3-oxo-2-(4-oxopentan-2-yl)-2,3-dihydrobenzofuran-2-carboxylate was obtained. Then, pyrrolidine (0.02 mol, 1.4 mg, 10 mol%) and benzoic acid (0.02 mmol, 2.4 mg, 10 mol%) were dissolved in DCM (4 ml), followed by the addition of methyl 3-oxo-2-(4-oxopentan-2-yl)-2,3-dihydrobenzofuran-2-carboxylate (0.2 mmol, 55.3 mg). The resulting mixture was stirred for a further 24 h at ambient temperature. After completion of the reaction, the solvent was evaporated under reduced pressure. The resulting crude mixture was purified by flash (ethyl acetate/hexane) on silica gel, giving the title compound. Single crystals were obtained by slow evaporation of a dichloromethane solution.
Refinement
Crystal data, data collection and structure .
details are summarized in Table 2Structural data
CCDC reference: 1524459
https://doi.org/10.1107/S2414314617003959/pk4014sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314617003959/pk4014Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2414314617003959/pk4014Isup3.cml
Data collection: APEX3 (Bruker, 2013); cell
SAINT (Bruker, 2013); data reduction: SAINT (Sheldrick, 2008); program(s) used to solve structure: SHELXS2013 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2015); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).C15H14O4 | F(000) = 544 |
Mr = 258.26 | Dx = 1.343 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
a = 7.5629 (19) Å | Cell parameters from 2301 reflections |
b = 8.205 (2) Å | θ = 5.4–51.1° |
c = 20.587 (5) Å | µ = 0.10 mm−1 |
β = 91.147 (5)° | T = 293 K |
V = 1277.3 (6) Å3 | Prismatic, yellow |
Z = 4 | 0.20 × 0.16 × 0.13 mm |
Bruker SMART CCD area detector diffractometer | 2060 reflections with I > 2σ(I) |
φ and ω scans | Rint = 0.029 |
Absorption correction: multi-scan (SADABS; Krause et al., 2015) | θmax = 26.0°, θmin = 2.0° |
Tmin = 0.636, Tmax = 0.746 | h = −8→9 |
7307 measured reflections | k = −10→6 |
2514 independent reflections | l = −25→21 |
Refinement on F2 | 0 restraints |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.043 | H-atom parameters constrained |
wR(F2) = 0.116 | w = 1/[σ2(Fo2) + (0.0544P)2 + 0.3361P] where P = (Fo2 + 2Fc2)/3 |
S = 1.04 | (Δ/σ)max < 0.001 |
2514 reflections | Δρmax = 0.23 e Å−3 |
174 parameters | Δρmin = −0.22 e Å−3 |
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. |
x | y | z | Uiso*/Ueq | ||
O1 | −0.0877 (2) | 0.9292 (3) | 0.22792 (8) | 0.0940 (6) | |
O2 | 0.32975 (13) | 0.60786 (13) | 0.06049 (5) | 0.0365 (3) | |
O3 | 0.55387 (16) | 0.85572 (17) | 0.06209 (7) | 0.0600 (4) | |
O4 | 0.37667 (15) | 1.01442 (15) | 0.12004 (6) | 0.0501 (3) | |
C1 | −0.0163 (2) | 0.8566 (2) | 0.12190 (8) | 0.0432 (4) | |
H1 | −0.1242 | 0.8931 | 0.1051 | 0.052* | |
C2 | 0.0203 (2) | 0.8695 (2) | 0.19168 (9) | 0.0517 (5) | |
C3 | 0.1928 (2) | 0.8018 (2) | 0.21819 (8) | 0.0467 (4) | |
H3A | 0.1706 | 0.7506 | 0.2597 | 0.056* | |
H3B | 0.2732 | 0.8920 | 0.2262 | 0.056* | |
C4 | 0.2851 (2) | 0.6774 (2) | 0.17467 (7) | 0.0397 (4) | |
H4 | 0.2137 | 0.5778 | 0.1751 | 0.048* | |
C5 | 0.28479 (19) | 0.73901 (18) | 0.10436 (7) | 0.0327 (3) | |
C6 | 0.10214 (18) | 0.79335 (17) | 0.08177 (7) | 0.0331 (3) | |
C7 | 0.08941 (19) | 0.74126 (18) | 0.01420 (7) | 0.0336 (3) | |
C8 | 0.22453 (19) | 0.62851 (18) | 0.00562 (7) | 0.0326 (3) | |
C9 | 0.2450 (2) | 0.5433 (2) | −0.05172 (7) | 0.0399 (4) | |
H9 | 0.3332 | 0.4655 | −0.0563 | 0.048* | |
C10 | 0.1270 (2) | 0.5802 (2) | −0.10195 (7) | 0.0456 (4) | |
H10 | 0.1378 | 0.5268 | −0.1415 | 0.055* | |
C11 | −0.0068 (2) | 0.6944 (2) | −0.09503 (8) | 0.0486 (4) | |
H11 | −0.0823 | 0.7174 | −0.1301 | 0.058* | |
C12 | −0.0291 (2) | 0.7744 (2) | −0.03651 (8) | 0.0433 (4) | |
H12 | −0.1210 | 0.8483 | −0.0313 | 0.052* | |
C13 | 0.4676 (3) | 0.6326 (3) | 0.20074 (9) | 0.0636 (6) | |
H13A | 0.5213 | 0.5560 | 0.1719 | 0.095* | |
H13B | 0.4577 | 0.5844 | 0.2430 | 0.095* | |
H13C | 0.5395 | 0.7288 | 0.2038 | 0.095* | |
C14 | 0.42267 (19) | 0.87457 (19) | 0.09257 (7) | 0.0359 (4) | |
C15 | 0.4953 (3) | 1.1509 (2) | 0.11045 (10) | 0.0623 (6) | |
H15A | 0.6117 | 1.1228 | 0.1262 | 0.093* | |
H15B | 0.4532 | 1.2440 | 0.1338 | 0.093* | |
H15C | 0.4996 | 1.1764 | 0.0650 | 0.093* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0928 (12) | 0.1214 (15) | 0.0686 (10) | 0.0423 (11) | 0.0225 (9) | −0.0275 (10) |
O2 | 0.0374 (6) | 0.0366 (6) | 0.0355 (6) | 0.0068 (5) | −0.0021 (4) | −0.0046 (4) |
O3 | 0.0409 (7) | 0.0634 (9) | 0.0763 (9) | −0.0093 (6) | 0.0183 (6) | −0.0091 (7) |
O4 | 0.0501 (7) | 0.0399 (7) | 0.0608 (7) | −0.0128 (5) | 0.0125 (6) | −0.0079 (6) |
C1 | 0.0340 (8) | 0.0410 (9) | 0.0548 (10) | 0.0033 (7) | 0.0039 (7) | −0.0048 (8) |
C2 | 0.0566 (11) | 0.0479 (10) | 0.0513 (10) | 0.0026 (8) | 0.0157 (8) | −0.0119 (8) |
C3 | 0.0581 (11) | 0.0477 (10) | 0.0346 (8) | −0.0037 (8) | 0.0085 (7) | −0.0038 (7) |
C4 | 0.0469 (9) | 0.0387 (8) | 0.0335 (8) | −0.0006 (7) | 0.0026 (7) | 0.0030 (7) |
C5 | 0.0336 (8) | 0.0323 (8) | 0.0323 (7) | 0.0022 (6) | 0.0018 (6) | −0.0030 (6) |
C6 | 0.0310 (7) | 0.0285 (7) | 0.0400 (8) | −0.0032 (6) | 0.0015 (6) | 0.0005 (6) |
C7 | 0.0331 (7) | 0.0309 (8) | 0.0366 (8) | −0.0053 (6) | 0.0002 (6) | 0.0027 (6) |
C8 | 0.0336 (7) | 0.0319 (8) | 0.0325 (7) | −0.0055 (6) | 0.0025 (6) | 0.0025 (6) |
C9 | 0.0441 (9) | 0.0371 (9) | 0.0387 (8) | −0.0050 (7) | 0.0075 (7) | −0.0029 (7) |
C10 | 0.0570 (10) | 0.0480 (10) | 0.0320 (8) | −0.0168 (8) | 0.0033 (7) | −0.0012 (7) |
C11 | 0.0538 (10) | 0.0519 (11) | 0.0396 (9) | −0.0117 (9) | −0.0124 (7) | 0.0088 (8) |
C12 | 0.0406 (9) | 0.0403 (9) | 0.0487 (9) | −0.0013 (7) | −0.0060 (7) | 0.0060 (7) |
C13 | 0.0703 (13) | 0.0781 (15) | 0.0421 (10) | 0.0174 (11) | −0.0085 (9) | 0.0066 (9) |
C14 | 0.0323 (8) | 0.0428 (9) | 0.0325 (7) | −0.0011 (7) | −0.0025 (6) | 0.0000 (6) |
C15 | 0.0677 (13) | 0.0484 (12) | 0.0709 (13) | −0.0261 (10) | 0.0046 (10) | −0.0042 (9) |
O1—C2 | 1.220 (2) | C6—C7 | 1.457 (2) |
O2—C8 | 1.3791 (17) | C7—C12 | 1.389 (2) |
O2—C5 | 1.4497 (17) | C7—C8 | 1.392 (2) |
O3—C14 | 1.1946 (19) | C8—C9 | 1.383 (2) |
O4—C14 | 1.3288 (19) | C9—C10 | 1.385 (2) |
O4—C15 | 1.451 (2) | C9—H9 | 0.9300 |
C1—C6 | 1.335 (2) | C10—C11 | 1.389 (3) |
C1—C2 | 1.461 (2) | C10—H10 | 0.9300 |
C1—H1 | 0.9300 | C11—C12 | 1.385 (2) |
C2—C3 | 1.510 (3) | C11—H11 | 0.9300 |
C3—C4 | 1.535 (2) | C12—H12 | 0.9300 |
C3—H3A | 0.9700 | C13—H13A | 0.9600 |
C3—H3B | 0.9700 | C13—H13B | 0.9600 |
C4—C13 | 1.516 (3) | C13—H13C | 0.9600 |
C4—C5 | 1.533 (2) | C15—H15A | 0.9600 |
C4—H4 | 0.9800 | C15—H15B | 0.9600 |
C5—C6 | 1.516 (2) | C15—H15C | 0.9600 |
C5—C14 | 1.547 (2) | ||
C8—O2—C5 | 106.28 (11) | C8—C7—C6 | 106.35 (12) |
C14—O4—C15 | 116.16 (14) | O2—C8—C9 | 124.37 (14) |
C6—C1—C2 | 121.34 (15) | O2—C8—C7 | 112.99 (12) |
C6—C1—H1 | 119.3 | C9—C8—C7 | 122.61 (14) |
C2—C1—H1 | 119.3 | C8—C9—C10 | 116.46 (15) |
O1—C2—C1 | 120.96 (18) | C8—C9—H9 | 121.8 |
O1—C2—C3 | 120.73 (17) | C10—C9—H9 | 121.8 |
C1—C2—C3 | 118.28 (14) | C9—C10—C11 | 122.02 (15) |
C2—C3—C4 | 115.69 (14) | C9—C10—H10 | 119.0 |
C2—C3—H3A | 108.4 | C11—C10—H10 | 119.0 |
C4—C3—H3A | 108.4 | C12—C11—C10 | 120.71 (15) |
C2—C3—H3B | 108.4 | C12—C11—H11 | 119.6 |
C4—C3—H3B | 108.4 | C10—C11—H11 | 119.6 |
H3A—C3—H3B | 107.4 | C11—C12—C7 | 118.21 (16) |
C13—C4—C5 | 113.48 (13) | C11—C12—H12 | 120.9 |
C13—C4—C3 | 112.11 (14) | C7—C12—H12 | 120.9 |
C5—C4—C3 | 109.88 (13) | C4—C13—H13A | 109.5 |
C13—C4—H4 | 107.0 | C4—C13—H13B | 109.5 |
C5—C4—H4 | 107.0 | H13A—C13—H13B | 109.5 |
C3—C4—H4 | 107.0 | C4—C13—H13C | 109.5 |
O2—C5—C6 | 104.53 (11) | H13A—C13—H13C | 109.5 |
O2—C5—C4 | 110.34 (12) | H13B—C13—H13C | 109.5 |
C6—C5—C4 | 111.77 (12) | O3—C14—O4 | 124.24 (15) |
O2—C5—C14 | 105.59 (11) | O3—C14—C5 | 123.97 (15) |
C6—C5—C14 | 110.69 (12) | O4—C14—C5 | 111.78 (12) |
C4—C5—C14 | 113.37 (12) | O4—C15—H15A | 109.5 |
C1—C6—C7 | 132.26 (14) | O4—C15—H15B | 109.5 |
C1—C6—C5 | 122.88 (14) | H15A—C15—H15B | 109.5 |
C7—C6—C5 | 104.42 (12) | O4—C15—H15C | 109.5 |
C12—C7—C8 | 119.92 (14) | H15A—C15—H15C | 109.5 |
C12—C7—C6 | 133.59 (15) | H15B—C15—H15C | 109.5 |
C6—C1—C2—O1 | 179.12 (19) | C5—C6—C7—C12 | −168.28 (17) |
C6—C1—C2—C3 | −2.9 (3) | C1—C6—C7—C8 | −156.31 (17) |
O1—C2—C3—C4 | 158.43 (19) | C5—C6—C7—C8 | 16.00 (15) |
C1—C2—C3—C4 | −19.5 (2) | C5—O2—C8—C9 | 169.92 (14) |
C2—C3—C4—C13 | 172.58 (16) | C5—O2—C8—C7 | −12.19 (16) |
C2—C3—C4—C5 | 45.4 (2) | C12—C7—C8—O2 | −179.36 (13) |
C8—O2—C5—C6 | 21.40 (14) | C6—C7—C8—O2 | −2.93 (16) |
C8—O2—C5—C4 | 141.71 (12) | C12—C7—C8—C9 | −1.4 (2) |
C8—O2—C5—C14 | −95.43 (12) | C6—C7—C8—C9 | 175.00 (13) |
C13—C4—C5—O2 | 68.04 (18) | O2—C8—C9—C10 | −179.94 (14) |
C3—C4—C5—O2 | −165.55 (12) | C7—C8—C9—C10 | 2.4 (2) |
C13—C4—C5—C6 | −176.09 (15) | C8—C9—C10—C11 | −1.1 (2) |
C3—C4—C5—C6 | −49.69 (17) | C9—C10—C11—C12 | −1.1 (3) |
C13—C4—C5—C14 | −50.15 (19) | C10—C11—C12—C7 | 2.1 (2) |
C3—C4—C5—C14 | 76.25 (16) | C8—C7—C12—C11 | −0.9 (2) |
C2—C1—C6—C7 | 167.82 (16) | C6—C7—C12—C11 | −176.13 (16) |
C2—C1—C6—C5 | −3.3 (2) | C15—O4—C14—O3 | 1.0 (2) |
O2—C5—C6—C1 | 150.30 (15) | C15—O4—C14—C5 | −178.52 (14) |
C4—C5—C6—C1 | 30.9 (2) | O2—C5—C14—O3 | −12.1 (2) |
C14—C5—C6—C1 | −96.46 (17) | C6—C5—C14—O3 | −124.64 (16) |
O2—C5—C6—C7 | −22.93 (14) | C4—C5—C14—O3 | 108.85 (17) |
C4—C5—C6—C7 | −142.28 (13) | O2—C5—C14—O4 | 167.49 (12) |
C14—C5—C6—C7 | 90.32 (14) | C6—C5—C14—O4 | 54.91 (16) |
C1—C6—C7—C12 | 19.4 (3) | C4—C5—C14—O4 | −71.60 (16) |
D—H···A | D—H | H···A | D···A | D—H···A |
C15—H15C···O3i | 0.96 | 2.65 | 3.565 (3) | 159 |
C9—H9···O2ii | 0.93 | 2.62 | 3.455 (2) | 149 |
C1—H1···O3iii | 0.93 | 2.59 | 3.453 (2) | 154 |
Symmetry codes: (i) −x+1, −y+2, −z; (ii) −x+1, −y+1, −z; (iii) x−1, y, z. |
Funding information
Funding for this research was provided by: Zhejiang Key Course of Chemical Engineering and Technology, Zhejiang University of Technology.
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