(E)-3-(2,3-Dimethoxyphenyl)-1-(2-hydroxy-4-methoxyphenyl)prop-2-en-1-one

Abstract

The mol­ecular conformation of the title compound, C₁₈H₁₈O₅, is stabilized by a strong intra­molecular hydrogen bond between the hydroxyl and carbonyl groups. The C=C double bond displays an E configuration while the carbonyl group shows an S-cis configuration relative to the double bond. The dihedral angle between the two rings is 15.0 (1)°.

Related literature

For related literature, see: Chu et al. (2004 ▶); Desiraju (2002 ▶); Fronczek et al. (1987 ▶); Radha Krishna et al. (2005 ▶); Rao et al. (2004 ▶); Shoja (1999 ▶); Subbiah Pandi et al. (2003 ▶); Usman et al. (2006 ▶); Wafo et al. (2005 ▶); Wallet et al. (1995 ▶); Wu et al. (2005 ▶).

Experimental

Crystal data

• C₁₈H₁₈O₅

• M _r = 314.32

• Monoclinic,

• a = 4.8793 (5) Å

• b = 24.283 (3) Å

• c = 13.0770 (14) Å

• β = 97.044 (2)°

• V = 1537.7 (3) ų

• Z = 4

• Mo Kα radiation

• μ = 0.10 mm⁻¹

• T = 150 (2) K

• 0.25 × 0.10 × 0.07 mm

Data collection

• Siemens SMART CCD area-detector diffractometer

• Absorption correction: multi-scan (SADABS; Bruker, 1999 ▶) T _min = 0.976, T _max = 0.993

• 9482 measured reflections

• 2717 independent reflections

• 1522 reflections with I > 2σ(I)

• R _int = 0.080

Refinement

• R[F ² > 2σ(F ²)] = 0.064

• wR(F ²) = 0.139

• S = 1.03

• 2717 reflections

• 212 parameters

• H-atom parameters constrained

• Δρ_max = 0.21 e Å⁻³

• Δρ_min = −0.16 e Å⁻³

Data collection: SMART-NT (Bruker, 2001 ▶); cell refinement: SAINT-NT (Bruker, 1999 ▶); data reduction: SAINT-NT; program(s) used to solve structure: SHELXTL-NT (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL-NT; molecular graphics: SHELXTL-NT; software used to prepare material for publication: SHELXTL-NT.

Supplementary Material

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O20—H20⋯O1	0.84	1.77	2.515 (3)	147

supplementary crystallographic information

Comment

From the synthetic point of view, 2'-hydroxy acetophenones are the choice precursors for the synthesis of 2'-hydroxychalcones trough the Claisen-Schmidt condensation with an aldehyde. Under such basic conditions (i.e. KOH), a proton is removed to form the enolate anion at the acetyl moiety. Interestingly, in such a condition the 2'-hydroxyl proton remains unaffected by the base. Deprotonation of this 2'-hydroxy group occurs only under the action of a strong base (i.e. hydride) if the methyl ketone's protons in the acetophenone are blocked, as for instance, in the form of a Chalcone.

This behavior is attributed to the intense H-bonding interaction between the 2'-hydroxyl proton and the acetyl moiety of the acetophenone, which is preserved in the derivatives like 2'-hydroxy-chalcones. This structural characteristic of the title compound has been recognized to play a key role in its biological activity and seems to be the basis to its potential as an anti carcinogenic agent. In fact 2'-hydroxychalcones have been found to be cytotoxic against human tumor cells. In the particular case of the title compound this was found to be a potent cytotoxic agent against human lymphocytic and also to monocytic cell linies (Rao et al., 2004). It has been also proved to be a potent antiproliferative agent against tumor cell lines without being more cytotoxic to normal cells (Rao et al., 2004).

The structure of the title compound displays two phenyl rings connected through a three carbon propenone moiety. As shown in Figure 1, one phenyl ring is substituted at positions 2 and 3 with methoxy groups, while the other is substituted at positions 2' and 4' with one hydroxy and one methoxy group respectively.

The hydroxy substitution at 2' produces a six-membered intramolecular O—H···O hydrogen bond with the keto group (Desiraju, 2002). This hydrogen bond is present with almost no exception through the series of compounds with this core, startintg with 2'-Hydroxy-4-methylchalcone (Shoja, 1999). This intramolecular bond leads the carbonyl group to display an S-cis configuration in relation to the double bond. The double bond displays an E configuration.

The molecule is significantly planar, as reflected in the values determined for the torsion angles. This is also true for molecules substituted with methoxy and/or hydroxy groups at different points of both phenyl sub-systems (Fronczek et al., 1987; Wallet et al., 1995; Subbiah Pandi et al., 2003; Chu et al., 2004; Wafo et al., 2005; Radha Krishna et al., 2005; Wu et al., 2005; Usman et al., 2006).

The packing shows no significant intermolecular hydrogen bonding.

Experimental

The title compound was prepared as follows: A solution of the 2,3-dimethoxybenzaldehyde, (7.34 mmol in ethanol, 20 ml) was added dropwise to a mixture of 2'-hydroxy-4'-methoxyacetophenone (7.34 mmol, in ethanol, 20 ml) and potassium hydroxide (2 g in 10 ml distilled water) with stirring. The mixture was allowed to react overnight, was then diluted with distilled water (200 ml), neutralized with hydrochloric acid and extracted with ethyl acetate (4 x 50 ml). The combined organic phases were concentrated in a rotatory evaporator, redissolved in ethanol and allowed to crystallize, as yellow crystals (31%); mp 98–101 °C.

Refinement

The hydrogen atoms positions were calculated after each cycle of refinement with SHELXL (Bruker,1999) using a riding model for each structure, with C—H distances in the range 0.95 to 0.98 Å. U_iso(H) values were set equal to 1.5U_eq of the parent carbon atom for methyl groups and 1.2U_eq for the others. The exception were the hydroxyl hydrogen atom which were located in the Fourier and then refined with the O—H distance constrained to be 0.84 Å and the U_eq free to refine.

Figures

Fig. 1.

Molecular structure diagramas for I showing numbering scheme. Displacement ellipsoids are at 33% probability level and H atoms are shown as spheres of arbitrary radii.

Crystal data

C18H18O5	F000 = 664
Mr = 314.32	Dx = 1.358 Mg m−3
Monoclinic, P21/c	Melting point: 98-101 οC K
Hall symbol: -P 2ybc	Mo Kα radiation λ = 0.71073 Å
a = 4.8793 (5) Å	Cell parameters from 935 reflections
b = 24.283 (3) Å	θ = 3.0–19.9º
c = 13.0770 (14) Å	µ = 0.10 mm−1
β = 97.044 (2)º	T = 150 (2) K
V = 1537.7 (3) Å3	Plate, orange
Z = 4	0.25 × 0.10 × 0.07 mm

Data collection

Siemens SMART CCD area-detector diffractometer	2717 independent reflections
Radiation source: fine-focus sealed tube	1522 reflections with I > 2σ(I)
Monochromator: graphite	Rint = 0.080
T = 150(2) K	θmax = 25.0º
phi and ω scans	θmin = 1.8º
Absorption correction: multi-scan(SADABS; Bruker, 1999)	h = −5→5
Tmin = 0.976, Tmax = 0.993	k = −28→28
9482 measured reflections	l = −15→15

Refinement

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.064	H-atom parameters constrained
wR(F2) = 0.139	w = 1/[σ2(Fo2) + (0.0553P)2] where P = (Fo2 + 2Fc2)/3
S = 1.03	(Δ/σ)max < 0.001
2717 reflections	Δρmax = 0.21 e Å−3
212 parameters	Δρmin = −0.16 e Å−3
Primary atom site location: structure-invariant direct methods	Extinction correction: none

Special details

Experimental. 0.3 ° between frames and 30 secs exposure (per frame)

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.

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

	x	y	z	Uiso*/Ueq
C100	0.5970 (6)	0.41587 (14)	0.7398 (2)	0.0353 (8)
O1	0.6194 (4)	0.45867 (9)	0.68878 (17)	0.0458 (6)
C200	0.3714 (6)	0.37731 (13)	0.7078 (2)	0.0353 (8)
H200	0.3422	0.3473	0.7518	0.042*
C300	0.2072 (6)	0.38252 (12)	0.6203 (2)	0.0375 (8)
H300	0.2417	0.4132	0.5787	0.045*
C1	−0.0221 (6)	0.34652 (12)	0.5798 (2)	0.0334 (8)
C2	−0.1667 (6)	0.35684 (13)	0.4845 (2)	0.0330 (8)
O2	−0.0892 (4)	0.40002 (9)	0.42551 (16)	0.0438 (6)
C20	−0.2738 (7)	0.44601 (13)	0.4198 (3)	0.0514 (10)
H20A	−0.4614	0.4336	0.3951	0.077*
H20B	−0.2152	0.4735	0.3720	0.077*
H20C	−0.2713	0.4625	0.4883	0.077*
C3	−0.3817 (6)	0.32244 (13)	0.4428 (2)	0.0373 (8)
O3	−0.5036 (5)	0.33541 (9)	0.34667 (17)	0.0504 (7)
C30	−0.7260 (7)	0.30177 (15)	0.3026 (3)	0.0552 (10)
H30A	−0.6599	0.2640	0.2951	0.083*
H30B	−0.7987	0.3163	0.2347	0.083*
H30C	−0.8726	0.3018	0.3475	0.083*
C4	−0.4506 (6)	0.27696 (13)	0.4990 (3)	0.0409 (9)
H4	−0.5951	0.2530	0.4715	0.049*
C5	−0.3078 (6)	0.26662 (13)	0.5953 (3)	0.0397 (8)
H5	−0.3561	0.2357	0.6339	0.048*
C6	−0.0971 (6)	0.30068 (13)	0.6354 (3)	0.0386 (8)
H6	−0.0009	0.2931	0.7015	0.046*
C1'	0.7965 (6)	0.40449 (13)	0.8300 (2)	0.0314 (7)
C6'	0.8088 (7)	0.35443 (13)	0.8848 (2)	0.0381 (8)
H6'	0.6777	0.3265	0.8635	0.046*
C5'	1.0022 (6)	0.34452 (13)	0.9674 (2)	0.0387 (8)
H5'	1.0067	0.3100	1.0018	0.046*
C4'	1.1930 (6)	0.38540 (14)	1.0010 (2)	0.0377 (8)
O4	1.3722 (4)	0.37200 (9)	1.08503 (16)	0.0454 (6)
C40	1.5663 (6)	0.41353 (14)	1.1273 (3)	0.0490 (9)
H40A	1.6879	0.4235	1.0760	0.074*
H40B	1.6772	0.3990	1.1890	0.074*
H40C	1.4652	0.4462	1.1458	0.074*
C3'	1.1901 (6)	0.43537 (13)	0.9511 (2)	0.0362 (8)
H3'	1.3179	0.4634	0.9749	0.043*
C2'	0.9974 (6)	0.44402 (13)	0.8654 (2)	0.0351 (8)
O20	1.0090 (4)	0.49305 (9)	0.81665 (18)	0.0453 (6)
H20	0.8938	0.4933	0.7634	0.046 (11)*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
C100	0.0270 (18)	0.040 (2)	0.0400 (19)	0.0031 (15)	0.0089 (15)	−0.0042 (16)
O1	0.0407 (14)	0.0398 (15)	0.0549 (15)	−0.0023 (11)	−0.0017 (11)	0.0059 (12)
C200	0.0277 (18)	0.037 (2)	0.0410 (19)	−0.0003 (15)	0.0057 (15)	−0.0033 (16)
C300	0.0309 (19)	0.035 (2)	0.048 (2)	0.0034 (15)	0.0100 (16)	−0.0035 (16)
C1	0.0270 (18)	0.0325 (19)	0.0414 (19)	0.0058 (15)	0.0070 (15)	−0.0060 (15)
C2	0.0237 (18)	0.0351 (19)	0.041 (2)	0.0032 (14)	0.0085 (15)	−0.0037 (16)
O2	0.0394 (14)	0.0424 (14)	0.0498 (14)	−0.0008 (12)	0.0067 (11)	0.0088 (12)
C20	0.054 (2)	0.038 (2)	0.061 (2)	0.0044 (18)	0.0015 (19)	0.0061 (18)
C3	0.0296 (19)	0.045 (2)	0.037 (2)	0.0013 (16)	0.0043 (16)	−0.0064 (16)
O3	0.0408 (14)	0.0594 (17)	0.0487 (15)	−0.0070 (12)	−0.0038 (12)	−0.0063 (13)
C30	0.040 (2)	0.067 (3)	0.057 (2)	−0.009 (2)	−0.0025 (18)	−0.021 (2)
C4	0.033 (2)	0.041 (2)	0.051 (2)	−0.0035 (16)	0.0113 (17)	−0.0148 (17)
C5	0.0344 (19)	0.033 (2)	0.053 (2)	0.0007 (16)	0.0106 (17)	−0.0048 (16)
C6	0.033 (2)	0.0360 (19)	0.047 (2)	0.0051 (16)	0.0060 (16)	0.0003 (17)
C1'	0.0231 (17)	0.039 (2)	0.0342 (18)	−0.0007 (15)	0.0100 (14)	−0.0062 (15)
C6'	0.0313 (19)	0.039 (2)	0.046 (2)	−0.0031 (16)	0.0104 (17)	−0.0017 (16)
C5'	0.0308 (19)	0.043 (2)	0.043 (2)	−0.0002 (16)	0.0077 (16)	0.0013 (17)
C4'	0.0278 (19)	0.046 (2)	0.0392 (19)	0.0019 (16)	0.0048 (16)	−0.0034 (17)
O4	0.0364 (13)	0.0522 (15)	0.0457 (14)	−0.0042 (12)	−0.0020 (11)	0.0029 (12)
C40	0.034 (2)	0.060 (2)	0.051 (2)	−0.0078 (18)	−0.0034 (17)	−0.0113 (19)
C3'	0.0290 (19)	0.040 (2)	0.0400 (19)	−0.0036 (15)	0.0047 (16)	−0.0064 (17)
C2'	0.0337 (19)	0.035 (2)	0.039 (2)	0.0008 (15)	0.0133 (16)	−0.0006 (16)
O20	0.0411 (14)	0.0414 (15)	0.0516 (16)	−0.0057 (11)	−0.0021 (13)	0.0028 (11)

Geometric parameters (Å, °)

C100—O1	1.247 (4)	O4—C40	1.446 (3)
C100—C1'	1.461 (4)	C3'—C2'	1.388 (4)
C100—C200	1.467 (4)	C2'—O20	1.355 (3)
C200—C300	1.319 (4)	C200—H200	0.9500
C300—C1	1.467 (4)	C300—H300	0.9500
C1—C2	1.377 (4)	C20—H20A	0.9800
C1—C6	1.403 (4)	C20—H20B	0.9800
C2—O2	1.382 (3)	C20—H20C	0.9800
C2—C3	1.398 (4)	C30—H30A	0.9800
O2—C20	1.431 (4)	C30—H30B	0.9800
C3—O3	1.360 (4)	C30—H30C	0.9800
C3—C4	1.391 (4)	C4—H4	0.9500
O3—C30	1.423 (3)	C5—H5	0.9500
C4—C5	1.385 (4)	C6—H6	0.9500
C5—C6	1.372 (4)	C6'—H6'	0.9500
C1'—C6'	1.409 (4)	C5'—H5'	0.9500
C1'—C2'	1.409 (4)	C40—H40A	0.9800
C6'—C5'	1.366 (4)	C40—H40B	0.9800
C5'—C4'	1.394 (4)	C40—H40C	0.9800
C4'—O4	1.357 (3)	C3'—H3'	0.9500
C4'—C3'	1.377 (4)	O20—H20	0.8400
O1—C100—C1'	119.7 (3)	C200—C300—H300	116.1
O1—C100—C200	119.4 (3)	C1—C300—H300	116.1
C1'—C100—C200	120.8 (3)	O2—C20—H20A	109.5
C300—C200—C100	122.8 (3)	O2—C20—H20B	109.5
C200—C300—C1	127.7 (3)	H20A—C20—H20B	109.5
C2—C1—C6	118.4 (3)	O2—C20—H20C	109.5
C2—C1—C300	120.1 (3)	H20A—C20—H20C	109.5
C6—C1—C300	121.4 (3)	H20B—C20—H20C	109.5
C1—C2—O2	119.9 (3)	O3—C30—H30A	109.5
C1—C2—C3	121.4 (3)	O3—C30—H30B	109.5
O2—C2—C3	118.7 (3)	H30A—C30—H30B	109.5
C2—O2—C20	114.1 (2)	O3—C30—H30C	109.5
O3—C3—C4	124.5 (3)	H30A—C30—H30C	109.5
O3—C3—C2	116.4 (3)	H30B—C30—H30C	109.5
C4—C3—C2	119.1 (3)	C5—C4—H4	120.1
C3—O3—C30	117.8 (3)	C3—C4—H4	120.1
C5—C4—C3	119.8 (3)	C6—C5—H5	119.7
C6—C5—C4	120.5 (3)	C4—C5—H5	119.7
C5—C6—C1	120.7 (3)	C5—C6—H6	119.6
C6'—C1'—C2'	115.9 (3)	C1—C6—H6	119.6
C6'—C1'—C100	123.8 (3)	C5'—C6'—H6'	118.8
C2'—C1'—C100	120.3 (3)	C1'—C6'—H6'	118.8
C5'—C6'—C1'	122.4 (3)	C6'—C5'—H5'	120.2
C6'—C5'—C4'	119.6 (3)	C4'—C5'—H5'	120.2
O4—C4'—C3'	124.3 (3)	O4—C40—H40A	109.5
O4—C4'—C5'	115.0 (3)	O4—C40—H40B	109.5
C3'—C4'—C5'	120.7 (3)	H40A—C40—H40B	109.5
C4'—O4—C40	118.0 (3)	O4—C40—H40C	109.5
C4'—C3'—C2'	118.9 (3)	H40A—C40—H40C	109.5
O20—C2'—C3'	116.7 (3)	H40B—C40—H40C	109.5
O20—C2'—C1'	120.8 (3)	C4'—C3'—H3'	120.6
C3'—C2'—C1'	122.5 (3)	C2'—C3'—H3'	120.6
C300—C200—H200	118.6	C2'—O20—H20	109.5
C100—C200—H200	118.6
O1—C100—C200—C300	7.8 (5)	C2—C1—C6—C5	0.6 (4)
C1'—C100—C200—C300	−171.6 (3)	C300—C1—C6—C5	−178.4 (3)
C100—C200—C300—C1	179.4 (3)	O1—C100—C1'—C6'	−171.9 (3)
C200—C300—C1—C2	−177.5 (3)	C200—C100—C1'—C6'	7.5 (4)
C200—C300—C1—C6	1.5 (5)	O1—C100—C1'—C2'	6.2 (4)
C6—C1—C2—O2	−176.8 (3)	C200—C100—C1'—C2'	−174.4 (3)
C300—C1—C2—O2	2.3 (4)	C2'—C1'—C6'—C5'	0.2 (4)
C6—C1—C2—C3	−0.7 (4)	C100—C1'—C6'—C5'	178.4 (3)
C300—C1—C2—C3	178.4 (3)	C1'—C6'—C5'—C4'	1.2 (4)
C1—C2—O2—C20	−107.3 (3)	C6'—C5'—C4'—O4	178.5 (3)
C3—C2—O2—C20	76.5 (3)	C6'—C5'—C4'—C3'	−0.7 (5)
C1—C2—C3—O3	−177.7 (3)	C3'—C4'—O4—C40	2.4 (4)
O2—C2—C3—O3	−1.6 (4)	C5'—C4'—O4—C40	−176.8 (3)
C1—C2—C3—C4	0.1 (4)	O4—C4'—C3'—C2'	179.6 (3)
O2—C2—C3—C4	176.2 (3)	C5'—C4'—C3'—C2'	−1.3 (4)
C4—C3—O3—C30	3.2 (4)	C4'—C3'—C2'—O20	−177.7 (3)
C2—C3—O3—C30	−179.0 (3)	C4'—C3'—C2'—C1'	2.8 (4)
O3—C3—C4—C5	178.2 (3)	C6'—C1'—C2'—O20	178.2 (3)
C2—C3—C4—C5	0.5 (4)	C100—C1'—C2'—O20	0.0 (4)
C3—C4—C5—C6	−0.6 (5)	C6'—C1'—C2'—C3'	−2.3 (4)
C4—C5—C6—C1	0.0 (5)	C100—C1'—C2'—C3'	179.5 (3)

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
O20—H20···O1	0.84	1.77	2.515 (3)	147