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In the title compound, C22H24ClNO5, the carbonyl group is in an s-cis configuration with respect to the olefinic double bond. In the crystal structure, there are weak π-stacking inter­actions but there are no significant inter­molecular hydrogen bonds.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536805029648/lh6493sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S1600536805029648/lh6493Isup2.hkl
Contains datablock I

CCDC reference: 287623

Key indicators

  • Single-crystal X-ray study
  • T = 296 K
  • Mean [sigma](C-C) = 0.004 Å
  • R factor = 0.043
  • wR factor = 0.088
  • Data-to-parameter ratio = 14.4

checkCIF/PLATON results

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Alert level B PLAT026_ALERT_3_B Ratio Observed / Unique Reflections too Low .... 39 Perc.
Alert level C PLAT230_ALERT_2_C Hirshfeld Test Diff for C17 - C18 .. 5.40 su PLAT720_ALERT_4_C Number of Unusual/Non-Standard Label(s) ........ 1
0 ALERT level A = In general: serious problem 1 ALERT level B = Potentially serious problem 2 ALERT level C = Check and explain 0 ALERT level G = General alerts; check 0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 1 ALERT type 2 Indicator that the structure model may be wrong or deficient 1 ALERT type 3 Indicator that the structure quality may be low 1 ALERT type 4 Improvement, methodology, query or suggestion

Comment top

Chalcones possess anti-inflammatory, antimalarial and antifertility activities, and are also reported as having antitumour activity (De Vincenzo et al., 1995; Christelle et al., 2001; Srinivas et al., 2003). With this in mind, a series of chalcones have been synthesized in our lab and have been evaluated for antitumor activity in vitro against various human tumor cell lines. Among them, the title compound has a broad antitumor spectrum and low micromolar IC50 ranging from 4.8 to 22.7 µmol L−1 against six human tumor cell lines. In order to obtain detailed information on its molecular conformation in the solid state, an X-ray structure determination of the title compound, (I), has been carried out.

The title molecule is illustrated in Fig. 1. The configuration of the carbonyl group with respect to the olefinic double bond is s-cis, which is the same as in two related structures (Ravishankar et al., 2003; Moorthi et al., 2005). The trans arrangement of the H atoms in the –CHCH– group is consistent with the solution-phase 1H NMR studies (J = 15.6 Hz; Li & Su, 1994). The atoms in the unsaturated ketone group are essentially planar in accordance with the π-electron conjugation. The exocyclic angles around C10 deviate from the normal trigonal value of 120°, with a larger C11—C10—C9 angle of 125.4 (3)° and a smaller C15—C10—C9 angle of 118.6 (3)°. This may be the result of the intramolecular O—H···O hydrogen bond (Table 1). In the crystal structure, the only intermolecular interactions present are weak π stacking, where the central aromatic ring (C10–C15) and the p-chlorobezene ring (C1–C6), from pairs of molecules related by centers of symmetry, are separated by a centroid–centroid distance of 3.660 (2) Å and a perpendicular distance of 3.49 Å (Fig. 2).

Experimental top

The title compound was obtained from phloroglucinol via the Hoesch reaction (Gulati et al., 1943), etherification (Juntend & Junte, 1988), Aldol condensation (Bu et al., 1997) and the Mannich reaction (Wilds et al., 1963). A crystal suitable for crystallographic study was obtained by slow crystallization from acetone at room temperature.

Refinement top

All C-bound H atoms were positioned geometrically and allowed to ride on their attached atoms, with C—H(CH), C—H(CH2) and C—H(CH3) distances of 0.93, 0.97 and 0.96 Å, respectively. The isotropic displacement parameters of the H atoms were fixed at 1.2Ueq of their parent atoms. The small ratio of observed to unique reflections (39%) can lower the precision of the structure. Treatment of OH group?

Computing details top

Data collection: XSCANS (Bruker, 1997); cell refinement: XSCANS; data reduction: SHELXTL (Bruker, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL and PLATON (Spek, 2003); software used to prepare material for publication: SHELXTL.

Figures top
[Figure 1] Fig. 1. View of (I), showing the atom-labelling scheme and displacement ellipsoids at the 40% probability level.
[Figure 2] Fig. 2. Packing diagram (PLATON; Spek, 2003) of (I), showing the weak π-stacking interactions in the center of the unit cell. H atoms have been omitted.
2'-Hydroxy-3'-(morpholin-4-yl-methyl)-4',6'-dimethoxy-2-chloro-chalcone top
Crystal data top
C22H24ClNO5F(000) = 1760
Mr = 417.89Dx = 1.336 Mg m3
Monoclinic, C2/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2ycCell parameters from 28 reflections
a = 13.408 (2) Åθ = 2.9–14.8°
b = 10.517 (2) ŵ = 0.22 mm1
c = 29.505 (6) ÅT = 296 K
β = 92.90 (2)°Plate, yellow
V = 4154.9 (13) Å30.60 × 0.50 × 0.12 mm
Z = 8
Data collection top
Siemens P4
diffractometer
1515 reflections with I > 2σ(I)
Radiation source: normal-focus sealed tubeRint = 0.033
Graphite monochromatorθmax = 25.5°, θmin = 1.4°
ω scansh = 016
Absorption correction: ψ scan
(SHELXTL; Bruker, 1997)
k = 012
Tmin = 0.874, Tmax = 0.974l = 3535
4451 measured reflections3 standard reflections every 97 reflections
3872 independent reflections intensity decay: 3.3%
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.043H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.088 w = 1/[σ2(Fo2) + (0.0262P)2]
where P = (Fo2 + 2Fc2)/3
S = 0.81(Δ/σ)max < 0.001
3872 reflectionsΔρmax = 0.17 e Å3
269 parametersΔρmin = 0.17 e Å3
0 restraintsExtinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.00184 (12)
Crystal data top
C22H24ClNO5V = 4154.9 (13) Å3
Mr = 417.89Z = 8
Monoclinic, C2/cMo Kα radiation
a = 13.408 (2) ŵ = 0.22 mm1
b = 10.517 (2) ÅT = 296 K
c = 29.505 (6) Å0.60 × 0.50 × 0.12 mm
β = 92.90 (2)°
Data collection top
Siemens P4
diffractometer
1515 reflections with I > 2σ(I)
Absorption correction: ψ scan
(SHELXTL; Bruker, 1997)
Rint = 0.033
Tmin = 0.874, Tmax = 0.9743 standard reflections every 97 reflections
4451 measured reflections intensity decay: 3.3%
3872 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0430 restraints
wR(F2) = 0.088H atoms treated by a mixture of independent and constrained refinement
S = 0.81Δρmax = 0.17 e Å3
3872 reflectionsΔρmin = 0.17 e Å3
269 parameters
Special details top

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 (Å2) top
xyzUiso*/Ueq
Cl0.38905 (6)0.72256 (10)0.55745 (3)0.0884 (4)
O10.63199 (16)0.8432 (2)0.17539 (7)0.0707 (7)
O20.60487 (15)0.8428 (2)0.43680 (7)0.0730 (7)
O30.81469 (14)0.5530 (2)0.44309 (7)0.0615 (6)
O40.95185 (14)0.7210 (2)0.30864 (6)0.0609 (6)
O50.66999 (16)0.9096 (2)0.36435 (7)0.0604 (7)
N0.76459 (17)0.8451 (2)0.25467 (8)0.0479 (7)
C10.4764 (2)0.6039 (3)0.57022 (10)0.0577 (9)
C20.4576 (3)0.5230 (4)0.60567 (11)0.0725 (11)
H20.40070.53400.62200.087*
C30.5227 (3)0.4269 (4)0.61656 (12)0.0839 (12)
H30.51030.37280.64060.101*
C40.6066 (3)0.4092 (3)0.59233 (12)0.0764 (11)
H40.65100.34370.59980.092*
C50.6239 (2)0.4908 (3)0.55662 (11)0.0623 (10)
H50.68090.47900.54040.075*
C60.5596 (2)0.5889 (3)0.54432 (10)0.0474 (8)
C70.5788 (2)0.6735 (3)0.50628 (9)0.0520 (9)
H70.53570.74200.50160.062*
C80.6509 (2)0.6616 (3)0.47827 (9)0.0510 (8)
H80.69610.59510.48260.061*
C90.6629 (2)0.7495 (3)0.44013 (9)0.0484 (8)
C100.73842 (19)0.7318 (3)0.40638 (9)0.0376 (7)
C110.8143 (2)0.6384 (3)0.40846 (9)0.0438 (8)
C120.88623 (19)0.6339 (3)0.37645 (9)0.0446 (8)
H120.93680.57330.37880.054*
C130.8825 (2)0.7198 (3)0.34101 (9)0.0438 (8)
C140.8086 (2)0.8115 (3)0.33573 (9)0.0415 (8)
C150.7394 (2)0.8170 (3)0.36919 (9)0.0444 (8)
C160.8082 (2)0.9018 (3)0.29663 (9)0.0496 (8)
H16A0.77030.97700.30390.060*
H16B0.87610.92810.29180.060*
C170.7802 (2)0.9274 (3)0.21557 (10)0.0706 (10)
H17A0.85110.94110.21260.085*
H17B0.74881.00930.22000.085*
C180.7359 (2)0.8658 (4)0.17340 (11)0.0826 (12)
H18A0.74730.92010.14760.099*
H18B0.76960.78560.16870.099*
C190.6156 (2)0.7666 (3)0.21359 (10)0.0646 (10)
H19A0.64570.68380.20930.077*
H19B0.54440.75430.21600.077*
C200.6583 (2)0.8237 (3)0.25688 (9)0.0577 (9)
H20A0.62520.90390.26240.069*
H20B0.64620.76710.28200.069*
C210.8948 (2)0.4643 (3)0.44885 (10)0.0739 (11)
H21A0.89760.41250.42220.089*
H21B0.88420.41130.47460.089*
H21C0.95670.50960.45360.089*
C221.0320 (2)0.6316 (3)0.31209 (10)0.0671 (10)
H22A1.06970.64410.34030.080*
H22B1.07470.64390.28730.080*
H22C1.00550.54680.31100.080*
H00.633 (2)0.906 (3)0.3890 (11)0.103 (14)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl0.0718 (6)0.1093 (8)0.0870 (7)0.0171 (6)0.0326 (5)0.0079 (7)
O10.0693 (16)0.0889 (18)0.0537 (14)0.0189 (14)0.0023 (12)0.0085 (14)
O20.0728 (16)0.0699 (16)0.0794 (17)0.0344 (14)0.0339 (13)0.0229 (14)
O30.0589 (13)0.0611 (15)0.0660 (15)0.0247 (12)0.0188 (11)0.0227 (13)
O40.0526 (13)0.0702 (16)0.0619 (14)0.0138 (12)0.0228 (11)0.0119 (12)
O50.0610 (14)0.0611 (16)0.0602 (16)0.0252 (13)0.0149 (13)0.0149 (13)
N0.0465 (16)0.0579 (17)0.0398 (15)0.0049 (14)0.0071 (12)0.0111 (14)
C10.060 (2)0.070 (3)0.044 (2)0.008 (2)0.0094 (17)0.0005 (19)
C20.070 (3)0.098 (3)0.050 (2)0.017 (2)0.011 (2)0.007 (2)
C30.095 (3)0.101 (4)0.055 (3)0.027 (3)0.006 (2)0.022 (2)
C40.089 (3)0.069 (3)0.069 (3)0.003 (2)0.011 (2)0.018 (2)
C50.066 (2)0.067 (3)0.054 (2)0.001 (2)0.0027 (19)0.005 (2)
C60.054 (2)0.047 (2)0.0407 (18)0.0059 (18)0.0040 (16)0.0011 (17)
C70.0490 (19)0.055 (2)0.053 (2)0.0050 (17)0.0067 (16)0.0006 (18)
C80.0486 (18)0.055 (2)0.050 (2)0.0147 (17)0.0114 (16)0.0083 (17)
C90.0451 (18)0.056 (2)0.045 (2)0.0017 (18)0.0058 (15)0.0010 (18)
C100.0382 (16)0.0392 (18)0.0354 (16)0.0072 (15)0.0036 (13)0.0019 (15)
C110.0452 (18)0.044 (2)0.0424 (19)0.0022 (16)0.0019 (16)0.0033 (17)
C120.0395 (18)0.047 (2)0.0482 (18)0.0101 (15)0.0054 (15)0.0007 (17)
C130.0413 (17)0.048 (2)0.0423 (19)0.0010 (17)0.0075 (15)0.0009 (17)
C140.0439 (18)0.041 (2)0.0399 (18)0.0034 (16)0.0034 (15)0.0045 (15)
C150.0419 (18)0.042 (2)0.049 (2)0.0084 (16)0.0040 (16)0.0017 (17)
C160.0466 (19)0.053 (2)0.049 (2)0.0010 (17)0.0046 (16)0.0087 (17)
C170.061 (2)0.097 (3)0.053 (2)0.001 (2)0.0028 (18)0.032 (2)
C180.067 (3)0.131 (4)0.051 (2)0.017 (2)0.012 (2)0.033 (2)
C190.065 (2)0.073 (3)0.056 (2)0.010 (2)0.0063 (19)0.004 (2)
C200.056 (2)0.071 (2)0.046 (2)0.0046 (19)0.0064 (17)0.0034 (18)
C210.076 (2)0.066 (2)0.080 (3)0.034 (2)0.013 (2)0.026 (2)
C220.051 (2)0.079 (3)0.073 (2)0.012 (2)0.0230 (18)0.001 (2)
Geometric parameters (Å, º) top
Cl—C11.740 (3)C9—C101.468 (3)
O1—C191.411 (3)C10—C111.413 (3)
O1—C181.417 (3)C10—C151.418 (3)
O2—C91.253 (3)C11—C121.385 (3)
O3—C111.360 (3)C12—C131.381 (3)
O3—C211.426 (3)C12—H120.9300
O4—C131.366 (3)C13—C141.386 (3)
O4—C221.427 (3)C14—C151.390 (3)
O5—C151.349 (3)C14—C161.494 (3)
O5—H00.90 (3)C16—H16A0.9700
N—C201.447 (3)C16—H16B0.9700
N—C171.466 (3)C17—C181.498 (4)
N—C161.469 (3)C17—H17A0.9700
C1—C21.382 (4)C17—H17B0.9700
C1—C61.393 (3)C18—H18A0.9700
C2—C31.363 (4)C18—H18B0.9700
C2—H20.9300C19—C201.499 (3)
C3—C41.376 (4)C19—H19A0.9700
C3—H30.9300C19—H19B0.9700
C4—C51.388 (4)C20—H20A0.9700
C4—H40.9300C20—H20B0.9700
C5—C61.381 (4)C21—H21A0.9600
C5—H50.9300C21—H21B0.9600
C6—C71.465 (4)C21—H21C0.9600
C7—C81.309 (3)C22—H22A0.9600
C7—H70.9300C22—H22B0.9600
C8—C91.472 (4)C22—H22C0.9600
C8—H80.9300
C19—O1—C18108.8 (2)C13—C14—C16120.3 (3)
C11—O3—C21119.7 (2)C15—C14—C16123.0 (3)
C13—O4—C22118.7 (2)O5—C15—C14115.9 (3)
C15—O5—H0107 (2)O5—C15—C10120.3 (2)
C20—N—C17107.9 (2)C14—C15—C10123.8 (3)
C20—N—C16112.1 (2)N—C16—C14112.2 (2)
C17—N—C16110.9 (2)N—C16—H16A109.2
C2—C1—C6121.8 (3)C14—C16—H16A109.2
C2—C1—Cl117.3 (3)N—C16—H16B109.2
C6—C1—Cl120.8 (3)C14—C16—H16B109.2
C3—C2—C1119.7 (3)H16A—C16—H16B107.9
C3—C2—H2120.1N—C17—C18109.4 (3)
C1—C2—H2120.1N—C17—H17A109.8
C2—C3—C4120.6 (4)C18—C17—H17A109.8
C2—C3—H3119.7N—C17—H17B109.8
C4—C3—H3119.7C18—C17—H17B109.8
C3—C4—C5118.9 (4)H17A—C17—H17B108.2
C3—C4—H4120.5O1—C18—C17112.8 (3)
C5—C4—H4120.5O1—C18—H18A109.0
C6—C5—C4122.3 (3)C17—C18—H18A109.0
C6—C5—H5118.8O1—C18—H18B109.0
C4—C5—H5118.8C17—C18—H18B109.0
C5—C6—C1116.6 (3)H18A—C18—H18B107.8
C5—C6—C7121.6 (3)O1—C19—C20112.6 (3)
C1—C6—C7121.9 (3)O1—C19—H19A109.1
C8—C7—C6126.1 (3)C20—C19—H19A109.1
C8—C7—H7116.9O1—C19—H19B109.1
C6—C7—H7116.9C20—C19—H19B109.1
C7—C8—C9122.4 (3)H19A—C19—H19B107.8
C7—C8—H8118.8N—C20—C19111.0 (2)
C9—C8—H8118.8N—C20—H20A109.4
O2—C9—C10119.5 (3)C19—C20—H20A109.4
O2—C9—C8117.4 (3)N—C20—H20B109.4
C10—C9—C8123.0 (3)C19—C20—H20B109.4
C11—C10—C15116.0 (2)H20A—C20—H20B108.0
C11—C10—C9125.4 (3)O3—C21—H21A109.5
C15—C10—C9118.6 (3)O3—C21—H21B109.5
O3—C11—C12120.9 (3)H21A—C21—H21B109.5
O3—C11—C10117.9 (2)O3—C21—H21C109.5
C12—C11—C10121.3 (3)H21A—C21—H21C109.5
C13—C12—C11119.6 (3)H21B—C21—H21C109.5
C13—C12—H12120.2O4—C22—H22A109.5
C11—C12—H12120.2O4—C22—H22B109.5
O4—C13—C12122.4 (3)H22A—C22—H22B109.5
O4—C13—C14115.0 (3)O4—C22—H22C109.5
C12—C13—C14122.6 (3)H22A—C22—H22C109.5
C13—C14—C15116.7 (3)H22B—C22—H22C109.5
C6—C1—C2—C31.3 (5)C22—O4—C13—C121.2 (4)
Cl—C1—C2—C3178.8 (3)C22—O4—C13—C14178.5 (2)
C1—C2—C3—C40.5 (5)C11—C12—C13—O4179.4 (3)
C2—C3—C4—C50.0 (5)C11—C12—C13—C140.4 (4)
C3—C4—C5—C60.3 (5)O4—C13—C14—C15177.1 (2)
C4—C5—C6—C11.1 (5)C12—C13—C14—C152.7 (4)
C4—C5—C6—C7179.5 (3)O4—C13—C14—C160.4 (4)
C2—C1—C6—C51.6 (4)C12—C13—C14—C16179.8 (3)
Cl—C1—C6—C5179.0 (2)C13—C14—C15—O5177.8 (2)
C2—C1—C6—C7179.0 (3)C16—C14—C15—O50.4 (4)
Cl—C1—C6—C71.6 (4)C13—C14—C15—C102.9 (4)
C5—C6—C7—C85.6 (5)C16—C14—C15—C10179.7 (3)
C1—C6—C7—C8175.1 (3)C11—C10—C15—O5179.9 (3)
C6—C7—C8—C9178.4 (3)C9—C10—C15—O52.3 (4)
C7—C8—C9—O24.5 (4)C11—C10—C15—C140.8 (4)
C7—C8—C9—C10175.1 (3)C9—C10—C15—C14178.5 (3)
O2—C9—C10—C11173.6 (3)C20—N—C16—C1468.8 (3)
C8—C9—C10—C116.8 (4)C17—N—C16—C14170.5 (2)
O2—C9—C10—C153.9 (4)C13—C14—C16—N80.9 (3)
C8—C9—C10—C15175.7 (3)C15—C14—C16—N101.8 (3)
C21—O3—C11—C125.4 (4)C20—N—C17—C1857.6 (3)
C21—O3—C11—C10174.4 (3)C16—N—C17—C18179.4 (2)
C15—C10—C11—O3178.6 (2)C19—O1—C18—C1757.4 (4)
C9—C10—C11—O33.9 (4)N—C17—C18—O159.6 (4)
C15—C10—C11—C121.6 (4)C18—O1—C19—C2056.0 (3)
C9—C10—C11—C12175.9 (3)C17—N—C20—C1957.3 (3)
O3—C11—C12—C13178.4 (3)C16—N—C20—C19179.6 (2)
C10—C11—C12—C131.8 (4)O1—C19—C20—N58.1 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O5—H0···O20.90 (3)1.62 (3)2.452 (3)152 (3)

Experimental details

Crystal data
Chemical formulaC22H24ClNO5
Mr417.89
Crystal system, space groupMonoclinic, C2/c
Temperature (K)296
a, b, c (Å)13.408 (2), 10.517 (2), 29.505 (6)
β (°) 92.90 (2)
V3)4154.9 (13)
Z8
Radiation typeMo Kα
µ (mm1)0.22
Crystal size (mm)0.60 × 0.50 × 0.12
Data collection
DiffractometerSiemens P4
diffractometer
Absorption correctionψ scan
(SHELXTL; Bruker, 1997)
Tmin, Tmax0.874, 0.974
No. of measured, independent and
observed [I > 2σ(I)] reflections
4451, 3872, 1515
Rint0.033
(sin θ/λ)max1)0.606
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.043, 0.088, 0.81
No. of reflections3872
No. of parameters269
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.17, 0.17

Computer programs: XSCANS (Bruker, 1997), XSCANS, SHELXTL (Bruker, 1997), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL and PLATON (Spek, 2003), SHELXTL.

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O5—H0···O20.90 (3)1.62 (3)2.452 (3)152 (3)
 

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