(E)-2-(3,5-Di­meth­oxy­benzyl­idene)indan-1-one

The title compound was prepared via a Claisen-Schmidt condensation through a solventless, green synthesis technique. The resulting crystals formed in the monoclinic space group P2₁/c, and adopting the common E configuration.

Abstract

The title chalcone, C₁₈H₁₆O₃, was prepared by a solventless base-promoted Claisen–Schmidt condensation and, upon recrystallization from ethanol, obtained in 56% yield. The dihedral angle between the indanone ring system and the benzene ring is 2.54 (4) ° and the C atoms of the methoxy groups deviate from the benzene ring by 0.087 (1) and 0.114 (1) Å. In the crystal, π-stacking is the predominant inter­molecular force, with the mol­ecules stacking into columns running parallel to the b axis of the unit cell.

Structure description

The chalcone family of compounds possess an aromatic α,β-unsaturated ketone functionality and can readily be formed by base-promoted condensation–dehydrations of an aromatic aldehyde and an aromatic ketone. They are important pharmacophore scaffolds and can possess anti-inflammatory, anti-fungal, anti-cancer, and anti-malarial biological activities (Singh et al., 2015 ▸, 2014 ▸; Berthelette et al., 1997 ▸). Additionally, the aromatic groups can be functionalized so as to produce other biological effects. The indanone family of compounds are biologically active compounds that are involved in steroid hormone biosynthesis and arachidonic acid metabolism pathways (Berthelette et al., 1997 ▸). In addition, indanone derivatives serve as scaffolds for a variety of heterocycles (Sloop et al., 2002 ▸, 2012 ▸).

The combination of these two potential pharmacophores using greener and more efficient synthesis pathways en route to a series of highly functionalized indanone-based chalcones is now being studied by our research group. The solvent-free Claisen–Schmidt reaction undertaken in Fig. 1 ▸ minimizes reaction toxicity, limits waste production and enables easier product isolation in many cases.

Figure 1.

Green synthesis scheme for indanone-based chalcones

In the title mol­ecule (Fig. 2 ▸), the dihedral angle between the indanone ring system and the benzene ring is 2.54 (4) ° and the C‘7 and C18 atoms of the methoxy groups deviate from the benzene ring by 0.087 (1) and 0.114 (1) Å, respectively. No unusual bond lengths or angles are noted after a routine Mogul geometry check (Bruno et al., 2004 ▸).

Figure 2.

Displacement ellipsoid plot of 1b. Ellipsoids are drawn at the 50% probability level.

The predominant supra­molecular feature of this structure (Fig. 3 ▸) are slipped stacking inter­actions. This consists of ring-over-atom pairings between the indanone ring and the 3-position of the di­meth­oxy­phenyl ring of a neighboring mol­ecule and generates a relatively close contact of 2.7 Å for the methyl­ene H atoms of the indanone ring to the adjacent mol­ecule.

Figure 3.

Packing diagram of 1b viewed along the b axis.

Structurally characterized 1b is consistent with known structures of similar indaneones. A search of the Cambridge Structural Database (Version 5.41, update of November 2019; Groom et al., 2016 ▸) gave 35 hits with a similar core structure. A defined three-dimensional parameter search on the distance between the carbonyl O atom and the phenyl ring gave a clear indication of the stereochemistry of the double bond. The title compound adopts the more common E isomer – along with 33 of the other structures published – indicated by an O—C distances 4.2 to 4.5 Å. Only two examples of Z isomers (O—C of 3.2 to 3.4 Å) exist [POWZUX (Zhou et al., 2009 ▸) and HAVLAR (Mori & Maeda, 1994 ▸)]. The latter has seven structure determinations as part of a light-driven solid-state isomerization study (Harada et al., 2009 ▸).

Synthesis and crystallization

A 25 mL beaker equipped with a stir bar was charged with 3,5-di­meth­oxy­benzaldehyde (0.50 g, 3.0 mmol) and warmed to 60°C. To the liquified aldehyde was added 1-indanone (0.40 g, 3.0 mmol) and solid NaOH (0.20 g, 3.8 mmol). The reaction mixture was stirred for 30 minutes at 60°C. The resulting reaction mixture was neutralized with 4 mL of 1 M HCl, the resulting residue was washed with several 1 mL aliquots of distilled water and the crude product (0.80 g, 95% yield) isolated via vacuum filtration. Recrystallization from 95% ethanol solution via slow evaporation afforded the target chalcone, (E)-2-(3,5-di­meth­oxy­benzyl­iden­yl)-1-indanone (1b) as colorless needles, (0.47 g, 56% yield). Melting range: 174–175°C. IR, ¹H and ¹³C NMR spectroscopy and single-crystal X-ray analysis (see supporting information) confirmed the product identity.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1 ▸.

Table 1. Experimental details.

Crystal data
Chemical formula	C18H16O3
M r	280.31
Crystal system, space group	Monoclinic, P21/c
Temperature (K)	100
a, b, c (Å)	7.7611 (4), 7.2894 (4), 24.0331 (13)
β (°)	93.5573 (12)
V (Å3)	1357.02 (13)
Z	4
Radiation type	Mo Kα
μ (mm−1)	0.09
Crystal size (mm)	0.39 × 0.12 × 0.05
Data collection
Diffractometer	Bruker-Nonius X8 Kappa APEXII
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 ▸)
T min, T max	0.95, 0.99
No. of measured, independent and observed [I > 2σ(I)] reflections	30838, 5231, 4087
R int	0.040
(sin θ/λ)max (Å−1)	0.772
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.044, 0.123, 1.02
No. of reflections	5231
No. of parameters	192
H-atom treatment	H-atom parameters constrained
Δρmax, Δρmin (e Å−3)	0.61, −0.24

Computer programs: Instrument Service, APEX3 and SAINT (Bruker, 2017 ▸), SHELXT (Sheldrick, 2015a ▸), SHELXL2016/6 (Sheldrick, 2015b ▸), Mercury (Macrae et al., 2020 ▸) and publCIF (Westrip, 2010 ▸).

Supplementary Material

CCDC reference: 1894469

Additional supporting information: crystallographic information; 3D view; checkCIF report

full crystallographic data

Crystal data

C18H16O3	F(000) = 592
Mr = 280.31	Dx = 1.372 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 7.7611 (4) Å	Cell parameters from 242 reflections
b = 7.2894 (4) Å	θ = 3.0–33.1°
c = 24.0331 (13) Å	µ = 0.09 mm−1
β = 93.5573 (12)°	T = 100 K
V = 1357.02 (13) Å3	Needle, colourless
Z = 4	0.39 × 0.12 × 0.05 mm

Data collection

Bruker-Nonius X8 Kappa APEXII diffractometer	5231 independent reflections
Radiation source: fine-focus sealed tube	4087 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.040
Detector resolution: 8.3333 pixels mm-1	θmax = 33.3°, θmin = 2.6°
phi and ω scans	h = −11→11
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	k = −11→11
Tmin = 0.95, Tmax = 0.99	l = −37→37
30838 measured reflections

Refinement

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)] = 0.044	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.123	H-atom parameters constrained
S = 1.02	w = 1/[σ2(Fo2) + (0.0695P)2 + 0.2851P] where P = (Fo2 + 2Fc2)/3
5231 reflections	(Δ/σ)max = 0.001
192 parameters	Δρmax = 0.61 e Å−3
0 restraints	Δρmin = −0.24 e Å−3

Special details

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.

Refinement. All hydrogen atoms were seen in the difference map of later refinements, but were placed at calculated positions and refined using a riding model, setting isotropic displacement parameters to 1.2 or 1.5 times that of the parent atom for ring H atoms and methyl groups respectively.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.47855 (9)	0.17474 (11)	0.33135 (3)	0.01698 (15)
O2	1.03362 (8)	0.10918 (10)	0.58143 (3)	0.01475 (14)
O3	0.48827 (9)	0.32457 (10)	0.64602 (3)	0.01472 (14)
C1	0.37431 (12)	0.23058 (12)	0.36368 (4)	0.01126 (16)
C2	0.40164 (11)	0.24728 (12)	0.42550 (4)	0.01007 (15)
C3	0.23699 (11)	0.31671 (12)	0.44870 (4)	0.01069 (16)
H3A	0.191109	0.227118	0.474981	0.013*
H3B	0.256199	0.435489	0.468075	0.013*
C4	0.11611 (11)	0.33843 (12)	0.39744 (4)	0.01048 (16)
C5	0.19615 (12)	0.29325 (12)	0.34906 (4)	0.01129 (16)
C6	0.11094 (12)	0.30860 (13)	0.29642 (4)	0.01457 (18)
H6	0.168019	0.279979	0.263676	0.017*
C7	−0.05951 (13)	0.36685 (14)	0.29328 (4)	0.01710 (19)
H7	−0.120329	0.378944	0.257935	0.021*
C8	−0.14259 (12)	0.40795 (13)	0.34182 (4)	0.01618 (18)
H8	−0.260325	0.444422	0.339062	0.019*
C9	−0.05538 (12)	0.39621 (12)	0.39403 (4)	0.01333 (17)
H9	−0.111664	0.427002	0.426756	0.016*
C10	0.55633 (12)	0.20333 (12)	0.44993 (4)	0.01049 (16)
H10	0.63798	0.160868	0.425033	0.013*
C11	0.62038 (11)	0.20978 (12)	0.50842 (4)	0.00944 (15)
C12	0.79305 (11)	0.15891 (12)	0.52012 (4)	0.01034 (15)
H12	0.86179	0.122965	0.490626	0.012*
C13	0.86425 (11)	0.16081 (12)	0.57468 (4)	0.01032 (15)
C14	0.76564 (11)	0.21385 (12)	0.61855 (4)	0.01067 (16)
H14	0.813948	0.214673	0.655848	0.013*
C15	0.59412 (11)	0.26573 (12)	0.60630 (4)	0.01004 (15)
C16	0.52038 (11)	0.26358 (12)	0.55215 (4)	0.01045 (15)
H16	0.40318	0.298291	0.544834	0.013*
C17	1.10933 (12)	0.09692 (13)	0.63704 (4)	0.01411 (17)
H17A	1.229061	0.054895	0.636091	0.021*
H17B	1.043717	0.009564	0.658384	0.021*
H17C	1.107152	0.217881	0.654776	0.021*
C18	0.54517 (13)	0.30032 (15)	0.70314 (4)	0.01596 (18)
H18A	0.57173	0.170604	0.710108	0.024*
H18B	0.453887	0.339485	0.726921	0.024*
H18C	0.648975	0.374224	0.711613	0.024*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O1	0.0152 (3)	0.0258 (4)	0.0101 (3)	0.0022 (3)	0.0025 (2)	−0.0029 (3)
O2	0.0093 (3)	0.0234 (3)	0.0114 (3)	0.0048 (2)	−0.0004 (2)	−0.0017 (2)
O3	0.0125 (3)	0.0249 (4)	0.0069 (3)	0.0053 (3)	0.0018 (2)	−0.0017 (2)
C1	0.0120 (4)	0.0128 (4)	0.0089 (4)	−0.0009 (3)	0.0004 (3)	−0.0003 (3)
C2	0.0117 (4)	0.0111 (4)	0.0074 (3)	−0.0006 (3)	0.0009 (3)	−0.0002 (3)
C3	0.0112 (4)	0.0120 (4)	0.0090 (3)	0.0004 (3)	0.0015 (3)	−0.0008 (3)
C4	0.0108 (4)	0.0096 (3)	0.0110 (4)	−0.0010 (3)	0.0002 (3)	0.0002 (3)
C5	0.0119 (4)	0.0119 (4)	0.0099 (4)	−0.0007 (3)	−0.0007 (3)	0.0004 (3)
C6	0.0155 (4)	0.0170 (4)	0.0109 (4)	−0.0010 (3)	−0.0017 (3)	0.0006 (3)
C7	0.0164 (4)	0.0177 (4)	0.0165 (4)	−0.0009 (3)	−0.0053 (3)	0.0025 (3)
C8	0.0121 (4)	0.0142 (4)	0.0218 (5)	0.0007 (3)	−0.0021 (3)	0.0023 (3)
C9	0.0116 (4)	0.0126 (4)	0.0159 (4)	0.0006 (3)	0.0012 (3)	0.0014 (3)
C10	0.0117 (4)	0.0116 (4)	0.0083 (3)	0.0002 (3)	0.0012 (3)	−0.0007 (3)
C11	0.0100 (4)	0.0097 (3)	0.0086 (3)	−0.0002 (3)	0.0006 (3)	−0.0004 (3)
C12	0.0110 (4)	0.0116 (4)	0.0086 (3)	0.0012 (3)	0.0016 (3)	−0.0005 (3)
C13	0.0089 (4)	0.0112 (4)	0.0109 (4)	0.0009 (3)	0.0007 (3)	−0.0002 (3)
C14	0.0103 (4)	0.0125 (4)	0.0092 (4)	0.0011 (3)	0.0004 (3)	−0.0005 (3)
C15	0.0101 (4)	0.0121 (4)	0.0080 (4)	0.0006 (3)	0.0017 (3)	−0.0010 (3)
C16	0.0094 (4)	0.0127 (4)	0.0093 (4)	0.0011 (3)	0.0003 (3)	−0.0004 (3)
C17	0.0123 (4)	0.0165 (4)	0.0132 (4)	0.0014 (3)	−0.0025 (3)	−0.0011 (3)
C18	0.0172 (4)	0.0238 (5)	0.0071 (4)	0.0020 (3)	0.0022 (3)	−0.0007 (3)

Geometric parameters (Å, º)

O1—C1	1.2255 (11)	C8—H8	0.95
O2—C13	1.3673 (11)	C9—H9	0.95
O2—C17	1.4289 (11)	C10—C11	1.4623 (12)
O3—C15	1.3665 (11)	C10—H10	0.95
O3—C18	1.4267 (11)	C11—C16	1.4006 (12)
C1—C5	1.4777 (13)	C11—C12	1.4020 (12)
C1—C2	1.4929 (12)	C12—C13	1.3912 (12)
C2—C10	1.3421 (12)	C12—H12	0.95
C2—C3	1.5127 (13)	C13—C14	1.3952 (12)
C3—C4	1.5098 (13)	C14—C15	1.3975 (12)
C3—H3A	0.99	C14—H14	0.95
C3—H3B	0.99	C15—C16	1.3890 (12)
C4—C5	1.3913 (12)	C16—H16	0.95
C4—C9	1.3935 (12)	C17—H17A	0.98
C5—C6	1.3951 (12)	C17—H17B	0.98
C6—C7	1.3869 (14)	C17—H17C	0.98
C6—H6	0.95	C18—H18A	0.98
C7—C8	1.3999 (15)	C18—H18B	0.98
C7—H7	0.95	C18—H18C	0.98
C8—C9	1.3908 (13)
C13—O2—C17	117.69 (7)	C2—C10—H10	114.6
C15—O3—C18	118.00 (7)	C11—C10—H10	114.6
O1—C1—C5	126.64 (8)	C16—C11—C12	119.40 (8)
O1—C1—C2	126.83 (8)	C16—C11—C10	123.99 (8)
C5—C1—C2	106.53 (7)	C12—C11—C10	116.61 (8)
C10—C2—C1	118.94 (8)	C13—C12—C11	120.34 (8)
C10—C2—C3	132.21 (8)	C13—C12—H12	119.8
C1—C2—C3	108.84 (7)	C11—C12—H12	119.8
C4—C3—C2	103.34 (7)	O2—C13—C12	115.58 (8)
C4—C3—H3A	111.1	O2—C13—C14	123.71 (8)
C2—C3—H3A	111.1	C12—C13—C14	120.70 (8)
C4—C3—H3B	111.1	C13—C14—C15	118.42 (8)
C2—C3—H3B	111.1	C13—C14—H14	120.8
H3A—C3—H3B	109.1	C15—C14—H14	120.8
C5—C4—C9	119.79 (8)	O3—C15—C16	115.30 (8)
C5—C4—C3	111.71 (8)	O3—C15—C14	122.96 (8)
C9—C4—C3	128.50 (8)	C16—C15—C14	121.73 (8)
C4—C5—C6	121.84 (8)	C15—C16—C11	119.40 (8)
C4—C5—C1	109.53 (8)	C15—C16—H16	120.3
C6—C5—C1	128.63 (8)	C11—C16—H16	120.3
C7—C6—C5	118.09 (9)	O2—C17—H17A	109.5
C7—C6—H6	121.0	O2—C17—H17B	109.5
C5—C6—H6	121.0	H17A—C17—H17B	109.5
C6—C7—C8	120.48 (9)	O2—C17—H17C	109.5
C6—C7—H7	119.8	H17A—C17—H17C	109.5
C8—C7—H7	119.8	H17B—C17—H17C	109.5
C9—C8—C7	121.00 (9)	O3—C18—H18A	109.5
C9—C8—H8	119.5	O3—C18—H18B	109.5
C7—C8—H8	119.5	H18A—C18—H18B	109.5
C8—C9—C4	118.77 (9)	O3—C18—H18C	109.5
C8—C9—H9	120.6	H18A—C18—H18C	109.5
C4—C9—H9	120.6	H18B—C18—H18C	109.5
C2—C10—C11	130.87 (8)
O1—C1—C2—C10	2.20 (14)	C3—C4—C9—C8	179.35 (9)
C5—C1—C2—C10	−178.24 (8)	C1—C2—C10—C11	178.55 (9)
O1—C1—C2—C3	−178.27 (9)	C3—C2—C10—C11	−0.85 (17)
C5—C1—C2—C3	1.28 (9)	C2—C10—C11—C16	1.67 (15)
C10—C2—C3—C4	179.41 (10)	C2—C10—C11—C12	−178.08 (9)
C1—C2—C3—C4	−0.03 (9)	C16—C11—C12—C13	0.36 (13)
C2—C3—C4—C5	−1.36 (9)	C10—C11—C12—C13	−179.87 (8)
C2—C3—C4—C9	179.02 (9)	C17—O2—C13—C12	−175.86 (8)
C9—C4—C5—C6	1.74 (14)	C17—O2—C13—C14	4.54 (13)
C3—C4—C5—C6	−177.92 (8)	C11—C12—C13—O2	−179.86 (8)
C9—C4—C5—C1	−178.10 (8)	C11—C12—C13—C14	−0.25 (13)
C3—C4—C5—C1	2.24 (10)	O2—C13—C14—C15	179.29 (8)
O1—C1—C5—C4	177.40 (9)	C12—C13—C14—C15	−0.29 (13)
C2—C1—C5—C4	−2.16 (10)	C18—O3—C15—C16	169.35 (8)
O1—C1—C5—C6	−2.42 (16)	C18—O3—C15—C14	−11.69 (13)
C2—C1—C5—C6	178.02 (9)	C13—C14—C15—O3	−178.18 (8)
C4—C5—C6—C7	−1.47 (14)	C13—C14—C15—C16	0.72 (13)
C1—C5—C6—C7	178.33 (9)	O3—C15—C16—C11	178.37 (8)
C5—C6—C7—C8	−0.26 (14)	C14—C15—C16—C11	−0.61 (13)
C6—C7—C8—C9	1.73 (15)	C12—C11—C16—C15	0.06 (13)
C7—C8—C9—C4	−1.46 (14)	C10—C11—C16—C15	−179.69 (8)
C5—C4—C9—C8	−0.24 (13)

Funding Statement

Funding for this research was provided by: GGC STEC 4500 Research Fund.