organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2414-3146

Methyl 4-methyl-2-oxo-3,4-di­hydro­dibenzo[b,d]furan-4a(2H)-carboxyl­ate

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aCatalytic Hydrogenation Research Center, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China
*Correspondence e-mail: wangyifeng@zjut.edu.cn

Edited by S. Parkin, University of Kentucky, USA (Received 6 March 2017; accepted 11 March 2017; online 17 March 2017)

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 envelope conformation 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 envelope conformation, 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.

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

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 annulation 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[Bergonzini, G. & Melchiorre, P. (2012). Angew. Chem. Int. Ed. 51, 971-974.]); Marco-Contelles et al. (2006[Marco-Contelles, J., do Carmo Carreiras, M., Rodríguez, C., Villarroya, M. & García, A. G. (2006). Chem. Rev. 106, 116-133.]); Yamanaka et al. (2012[Yamanaka, M., Hoshino, M., Katoh, T., Mori, K. & Akiyama, T. (2012). Eur. J. Org. Chem. pp. 4508-4514.]).

The mol­ecular structure of the title compound (Fig. 1[link]) has a fused three-ring system comprising benzene and cyclo­hexenone fused to a central furan. The furan ring exhibits an envelope conformation, 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 envelope conformation, 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.

[Figure 1]
Figure 1
The structure of the title compound. Displacement ellipsoids are drawn at the 50% probability level.

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[link] and Fig. 2[link]).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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.
[Figure 2]
Figure 2
The crystal packing of the title compound viewed down the a axis. Hydrogen bonds are shown as dashed lines.

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 column chromatography (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 column chromatography (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 refinement details are summarized in Table 2[link].

Table 2
Experimental details

Crystal data
Chemical formula C15H14O4
Mr 258.26
Crystal system, space group Monoclinic, P21/c
Temperature (K) 293
a, b, c (Å) 7.5629 (19), 8.205 (2), 20.587 (5)
β (°) 91.147 (5)
V3) 1277.3 (6)
Z 4
Radiation type Mo Kα
μ (mm−1) 0.10
Crystal size (mm) 0.20 × 0.16 × 0.13
 
Data collection
Diffractometer Bruker SMART CCD area detector
Absorption correction Multi-scan (SADABS; Krause et al., 2015[Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3-10.])
Tmin, Tmax 0.636, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections 7307, 2514, 2060
Rint 0.029
(sin θ/λ)max−1) 0.617
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.043, 0.116, 1.04
No. of reflections 2514
No. of parameters 174
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.23, −0.22
Computer programs: APEX3 and SAINT (Bruker, 2013[Bruker (2013). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXTL and SHELXS2013 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]) and SHELXL2013 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]).

Structural data


Computing details top

Data collection: APEX3 (Bruker, 2013); cell refinement: 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).

Methyl 4-methyl-2-oxo-3,4-dihydrodibenzo[b,d]furan-4a(2H)-carboxylate top
Crystal data top
C15H14O4F(000) = 544
Mr = 258.26Dx = 1.343 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 7.5629 (19) ÅCell parameters from 2301 reflections
b = 8.205 (2) Åθ = 5.4–51.1°
c = 20.587 (5) ŵ = 0.10 mm1
β = 91.147 (5)°T = 293 K
V = 1277.3 (6) Å3Prismatic, yellow
Z = 40.20 × 0.16 × 0.13 mm
Data collection top
Bruker SMART CCD area detector
diffractometer
2060 reflections with I > 2σ(I)
φ and ω scansRint = 0.029
Absorption correction: multi-scan
(SADABS; Krause et al., 2015)
θmax = 26.0°, θmin = 2.0°
Tmin = 0.636, Tmax = 0.746h = 89
7307 measured reflectionsk = 106
2514 independent reflectionsl = 2521
Refinement top
Refinement on F20 restraints
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.043H-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 reflectionsΔρmax = 0.23 e Å3
174 parametersΔρmin = 0.22 e Å3
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.0877 (2)0.9292 (3)0.22792 (8)0.0940 (6)
O20.32975 (13)0.60786 (13)0.06049 (5)0.0365 (3)
O30.55387 (16)0.85572 (17)0.06209 (7)0.0600 (4)
O40.37667 (15)1.01442 (15)0.12004 (6)0.0501 (3)
C10.0163 (2)0.8566 (2)0.12190 (8)0.0432 (4)
H10.12420.89310.10510.052*
C20.0203 (2)0.8695 (2)0.19168 (9)0.0517 (5)
C30.1928 (2)0.8018 (2)0.21819 (8)0.0467 (4)
H3A0.17060.75060.25970.056*
H3B0.27320.89200.22620.056*
C40.2851 (2)0.6774 (2)0.17467 (7)0.0397 (4)
H40.21370.57780.17510.048*
C50.28479 (19)0.73901 (18)0.10436 (7)0.0327 (3)
C60.10214 (18)0.79335 (17)0.08177 (7)0.0331 (3)
C70.08941 (19)0.74126 (18)0.01420 (7)0.0336 (3)
C80.22453 (19)0.62851 (18)0.00562 (7)0.0326 (3)
C90.2450 (2)0.5433 (2)0.05172 (7)0.0399 (4)
H90.33320.46550.05630.048*
C100.1270 (2)0.5802 (2)0.10195 (7)0.0456 (4)
H100.13780.52680.14150.055*
C110.0068 (2)0.6944 (2)0.09503 (8)0.0486 (4)
H110.08230.71740.13010.058*
C120.0291 (2)0.7744 (2)0.03651 (8)0.0433 (4)
H120.12100.84830.03130.052*
C130.4676 (3)0.6326 (3)0.20074 (9)0.0636 (6)
H13A0.52130.55600.17190.095*
H13B0.45770.58440.24300.095*
H13C0.53950.72880.20380.095*
C140.42267 (19)0.87457 (19)0.09257 (7)0.0359 (4)
C150.4953 (3)1.1509 (2)0.11045 (10)0.0623 (6)
H15A0.61171.12280.12620.093*
H15B0.45321.24400.13380.093*
H15C0.49961.17640.06500.093*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0928 (12)0.1214 (15)0.0686 (10)0.0423 (11)0.0225 (9)0.0275 (10)
O20.0374 (6)0.0366 (6)0.0355 (6)0.0068 (5)0.0021 (4)0.0046 (4)
O30.0409 (7)0.0634 (9)0.0763 (9)0.0093 (6)0.0183 (6)0.0091 (7)
O40.0501 (7)0.0399 (7)0.0608 (7)0.0128 (5)0.0125 (6)0.0079 (6)
C10.0340 (8)0.0410 (9)0.0548 (10)0.0033 (7)0.0039 (7)0.0048 (8)
C20.0566 (11)0.0479 (10)0.0513 (10)0.0026 (8)0.0157 (8)0.0119 (8)
C30.0581 (11)0.0477 (10)0.0346 (8)0.0037 (8)0.0085 (7)0.0038 (7)
C40.0469 (9)0.0387 (8)0.0335 (8)0.0006 (7)0.0026 (7)0.0030 (7)
C50.0336 (8)0.0323 (8)0.0323 (7)0.0022 (6)0.0018 (6)0.0030 (6)
C60.0310 (7)0.0285 (7)0.0400 (8)0.0032 (6)0.0015 (6)0.0005 (6)
C70.0331 (7)0.0309 (8)0.0366 (8)0.0053 (6)0.0002 (6)0.0027 (6)
C80.0336 (7)0.0319 (8)0.0325 (7)0.0055 (6)0.0025 (6)0.0025 (6)
C90.0441 (9)0.0371 (9)0.0387 (8)0.0050 (7)0.0075 (7)0.0029 (7)
C100.0570 (10)0.0480 (10)0.0320 (8)0.0168 (8)0.0033 (7)0.0012 (7)
C110.0538 (10)0.0519 (11)0.0396 (9)0.0117 (9)0.0124 (7)0.0088 (8)
C120.0406 (9)0.0403 (9)0.0487 (9)0.0013 (7)0.0060 (7)0.0060 (7)
C130.0703 (13)0.0781 (15)0.0421 (10)0.0174 (11)0.0085 (9)0.0066 (9)
C140.0323 (8)0.0428 (9)0.0325 (7)0.0011 (7)0.0025 (6)0.0000 (6)
C150.0677 (13)0.0484 (12)0.0709 (13)0.0261 (10)0.0046 (10)0.0042 (9)
Geometric parameters (Å, º) top
O1—C21.220 (2)C6—C71.457 (2)
O2—C81.3791 (17)C7—C121.389 (2)
O2—C51.4497 (17)C7—C81.392 (2)
O3—C141.1946 (19)C8—C91.383 (2)
O4—C141.3288 (19)C9—C101.385 (2)
O4—C151.451 (2)C9—H90.9300
C1—C61.335 (2)C10—C111.389 (3)
C1—C21.461 (2)C10—H100.9300
C1—H10.9300C11—C121.385 (2)
C2—C31.510 (3)C11—H110.9300
C3—C41.535 (2)C12—H120.9300
C3—H3A0.9700C13—H13A0.9600
C3—H3B0.9700C13—H13B0.9600
C4—C131.516 (3)C13—H13C0.9600
C4—C51.533 (2)C15—H15A0.9600
C4—H40.9800C15—H15B0.9600
C5—C61.516 (2)C15—H15C0.9600
C5—C141.547 (2)
C8—O2—C5106.28 (11)C8—C7—C6106.35 (12)
C14—O4—C15116.16 (14)O2—C8—C9124.37 (14)
C6—C1—C2121.34 (15)O2—C8—C7112.99 (12)
C6—C1—H1119.3C9—C8—C7122.61 (14)
C2—C1—H1119.3C8—C9—C10116.46 (15)
O1—C2—C1120.96 (18)C8—C9—H9121.8
O1—C2—C3120.73 (17)C10—C9—H9121.8
C1—C2—C3118.28 (14)C9—C10—C11122.02 (15)
C2—C3—C4115.69 (14)C9—C10—H10119.0
C2—C3—H3A108.4C11—C10—H10119.0
C4—C3—H3A108.4C12—C11—C10120.71 (15)
C2—C3—H3B108.4C12—C11—H11119.6
C4—C3—H3B108.4C10—C11—H11119.6
H3A—C3—H3B107.4C11—C12—C7118.21 (16)
C13—C4—C5113.48 (13)C11—C12—H12120.9
C13—C4—C3112.11 (14)C7—C12—H12120.9
C5—C4—C3109.88 (13)C4—C13—H13A109.5
C13—C4—H4107.0C4—C13—H13B109.5
C5—C4—H4107.0H13A—C13—H13B109.5
C3—C4—H4107.0C4—C13—H13C109.5
O2—C5—C6104.53 (11)H13A—C13—H13C109.5
O2—C5—C4110.34 (12)H13B—C13—H13C109.5
C6—C5—C4111.77 (12)O3—C14—O4124.24 (15)
O2—C5—C14105.59 (11)O3—C14—C5123.97 (15)
C6—C5—C14110.69 (12)O4—C14—C5111.78 (12)
C4—C5—C14113.37 (12)O4—C15—H15A109.5
C1—C6—C7132.26 (14)O4—C15—H15B109.5
C1—C6—C5122.88 (14)H15A—C15—H15B109.5
C7—C6—C5104.42 (12)O4—C15—H15C109.5
C12—C7—C8119.92 (14)H15A—C15—H15C109.5
C12—C7—C6133.59 (15)H15B—C15—H15C109.5
C6—C1—C2—O1179.12 (19)C5—C6—C7—C12168.28 (17)
C6—C1—C2—C32.9 (3)C1—C6—C7—C8156.31 (17)
O1—C2—C3—C4158.43 (19)C5—C6—C7—C816.00 (15)
C1—C2—C3—C419.5 (2)C5—O2—C8—C9169.92 (14)
C2—C3—C4—C13172.58 (16)C5—O2—C8—C712.19 (16)
C2—C3—C4—C545.4 (2)C12—C7—C8—O2179.36 (13)
C8—O2—C5—C621.40 (14)C6—C7—C8—O22.93 (16)
C8—O2—C5—C4141.71 (12)C12—C7—C8—C91.4 (2)
C8—O2—C5—C1495.43 (12)C6—C7—C8—C9175.00 (13)
C13—C4—C5—O268.04 (18)O2—C8—C9—C10179.94 (14)
C3—C4—C5—O2165.55 (12)C7—C8—C9—C102.4 (2)
C13—C4—C5—C6176.09 (15)C8—C9—C10—C111.1 (2)
C3—C4—C5—C649.69 (17)C9—C10—C11—C121.1 (3)
C13—C4—C5—C1450.15 (19)C10—C11—C12—C72.1 (2)
C3—C4—C5—C1476.25 (16)C8—C7—C12—C110.9 (2)
C2—C1—C6—C7167.82 (16)C6—C7—C12—C11176.13 (16)
C2—C1—C6—C53.3 (2)C15—O4—C14—O31.0 (2)
O2—C5—C6—C1150.30 (15)C15—O4—C14—C5178.52 (14)
C4—C5—C6—C130.9 (2)O2—C5—C14—O312.1 (2)
C14—C5—C6—C196.46 (17)C6—C5—C14—O3124.64 (16)
O2—C5—C6—C722.93 (14)C4—C5—C14—O3108.85 (17)
C4—C5—C6—C7142.28 (13)O2—C5—C14—O4167.49 (12)
C14—C5—C6—C790.32 (14)C6—C5—C14—O454.91 (16)
C1—C6—C7—C1219.4 (3)C4—C5—C14—O471.60 (16)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C15—H15C···O3i0.962.653.565 (3)159
C9—H9···O2ii0.932.623.455 (2)149
C1—H1···O3iii0.932.593.453 (2)154
Symmetry codes: (i) x+1, y+2, z; (ii) x+1, y+1, z; (iii) x1, y, z.
 

Funding information

Funding for this research was provided by: Zhejiang Key Course of Chemical Engineering and Technology, Zhejiang University of Technology.

References

First citationBergonzini, G. & Melchiorre, P. (2012). Angew. Chem. Int. Ed. 51, 971–974.  CSD CrossRef CAS Google Scholar
First citationBruker (2013). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationKrause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3–10.  Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
First citationMarco-Contelles, J., do Carmo Carreiras, M., Rodríguez, C., Villarroya, M. & García, A. G. (2006). Chem. Rev. 106, 116–133.  PubMed CAS Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationYamanaka, M., Hoshino, M., Katoh, T., Mori, K. & Akiyama, T. (2012). Eur. J. Org. Chem. pp. 4508–4514.  CrossRef Google Scholar

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