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

Jiang, Y.; Wang, Y.

doi:10.1107/S2414314617003959

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 2| Part 3| March 2017| x170395

https://doi.org/10.1107/S2414314617003959

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

Yidong Jiang ^a and Yifeng Wang ^a ^*

^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.

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 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 ); 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 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
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 and Fig. 2).

Table 1
Hydrogen-bond geometry (Å, °)

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.

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.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₅H₁₄O₄
M_r	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)
V (Å³)	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 )
T_min, T_max	0.636, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections	7307, 2514, 2060
R_int	0.029
(sin θ/λ)_max (Å⁻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
Δρ_max, Δρ_min (e Å⁻³)	0.23, −0.22
Computer programs: APEX3 and SAINT (Bruker, 2013 ), SHELXTL and SHELXS2013 (Sheldrick, 2008 ) and SHELXL2013 (Sheldrick, 2015 ).

Structural data

CCDC reference: 1524459

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314617003959/pk4014sup1.cif

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

checkCIF report

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

C₁₅H₁₄O₄	F(000) = 544
M_r = 258.26	D_x = 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

Data collection top

Bruker SMART CCD area detector diffractometer	2060 reflections with I > 2σ(I)
φ and ω scans	R_int = 0.029
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	θ_max = 26.0°, θ_min = 2.0°
T_min = 0.636, T_max = 0.746	h = −8→9
7307 measured reflections	k = −10→6
2514 independent reflections	l = −25→21

Refinement top

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(F_o²) + (0.0544P)² + 0.3361P] where P = (F_o² + 2F_c²)/3
S = 1.04	(Δ/σ)_max < 0.001
2514 reflections	Δρ_max = 0.23 e Å⁻³
174 parameters	Δρ_min = −0.22 e Å⁻³

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

	x	y	z	U_iso*/U_eq
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*

Atomic displacement parameters (Å²) top

	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)

Geometric parameters (Å, º) top

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)

Hydrogen-bond geometry (Å, º) top

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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