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Acta Crystallogr Sect E Struct Rep Online. 2010 September 1; 66(Pt 9): o2284.
Published online 2010 August 11. doi:  10.1107/S1600536810031247
PMCID: PMC3007827

1-Chloro­acetyl-2,6-bis­(2-chloro­phen­yl)-3,5-dimethyl­piperidin-4-one

Abstract

In the title compound, C21H20Cl3NO2, the piperidin-4-one ring adopts a boat conformation. The two 2-chloro­phenyl groups are approximately perpendicular to each other, making a dihedral angle of 74.07 (8)°.

Related literature

For the biological activity of related structures, see: Parthiban et al. (2009 [triangle]); Aridoss et al. (2007 [triangle]). For spectroscopic studies of piperidin-4-ones, see: Ravindran et al. (1991 [triangle]); Krishnakumar et al. (1996 [triangle]). For ring conformational analysis, see: Cremer & Pople (1975 [triangle]); Nardelli (1983 [triangle]). For the synthesis of the title compound, see: Ramachandran et al. (2008 [triangle]); Aridoss et al. (2010 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o2284-scheme1.jpg

Experimental

Crystal data

  • C21H20Cl3NO2
  • M r = 424.73
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o2284-efi1.jpg
  • a = 11.6295 (4) Å
  • b = 9.6955 (3) Å
  • c = 17.4743 (5) Å
  • β = 90.481 (1)°
  • V = 1970.22 (11) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.48 mm−1
  • T = 293 K
  • 0.22 × 0.16 × 0.16 mm

Data collection

  • Bruker Kappa APEXII CCD diffractometer
  • Absorption correction: multi-scan (Blessing, 1995 [triangle]) T min = 0.901, T max = 0.927
  • 27536 measured reflections
  • 6864 independent reflections
  • 4998 reflections with I > 2σ(I)
  • R int = 0.023

Refinement

  • R[F 2 > 2σ(F 2)] = 0.045
  • wR(F 2) = 0.141
  • S = 1.01
  • 6864 reflections
  • 244 parameters
  • H-atom parameters constrained
  • Δρmax = 0.40 e Å−3
  • Δρmin = −0.31 e Å−3

Data collection: APEX2 (Bruker, 2004 [triangle]); cell refinement: APEX2 and SAINT (Bruker, 2004 [triangle]); data reduction: SAINT and XPREP (Bruker, 2004 [triangle]); program(s) used to solve structure: SIR92 (Altomare et al., 1993 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 (Farrugia, 1997 [triangle]); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810031247/ez2226sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810031247/ez2226Isup2.hkl

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

Acknowledgments

RR and YTJ are grateful for the support provided by the Industrial Technology Development Program–Ministry of Knowledge Economy of the Korean Government and 2010 Post-Doc. Research Program funded by Pukyong National University. The authors are thankful to the SAIF, Indian Institute of Technology, Madras, for the data collection.

supplementary crystallographic information

Comment

2,6-Disubstituted piperidones and their N-substituted compounds are of great interest due to their significant pharmacological properties (Parthiban et al., 2009; Aridoss et al., 2007). The introduction of electron withdrawing groups such as –CHO, COCH3, COPh, NO, etc., at the ring nitrogen cause a major change in ring conformation (Ravindran et al., 1991; Krishnakumar et al., 1996). Hence, we introduced the chloroacetyl (COCH2Cl) group into the piperidine ring in order to analyse the ring conformation through a single-crystal X-ray diffraction study.

In the molecular structure (C21H20Cl2NO2), the piperidine ring adopts a boat conformation with puckering parameters (Cremer & Pople, 1975) as follows: Total puckering amplitude, QT=0.6960 (15)Å and phase angle θ=85.52 (12)°. The smallest displacement asymmetry parameters (Nardelli, 1983) q1 and q2 are 0.6939 (15) Å and 0.0544 (15) Å, respectively. The dihedral angle between the two o-chlorophenyl rings is 74.07 (8) °.

Experimental

The title compound was obtained by adopting an earlier method (Ramachandran et al. (2008); Aridoss et al., 2010). To a well stirred solution of 3,5-dimethyl-2,6-bis(o-chloroyphenyl)piperidin-4-one (2 g, 4.71 mmol) and triethylamine (1.42 g, 14.13 mmol) in freshly distilled benzene (50 ml), chloroacetyl chloride (0.79 g, 7.06 mmol) in benzene (10 ml) was added drop-wise through the addition funnel over about half an hour. Stirring was continued until the completion of reaction. The reaction mixture was then poured into water and extracted with DCM. The solvent was removed under reduced pressure. The crude sample was purified by column chromatography. Upon recrystallization from absolute ethanol this afforded fine white crystals suitable for X-ray diffraction analysis.

Refinement

H-atoms were positioned and refined using a riding model, with aromatic C—H = 0.93 Å, methine C—H = 0.98 Å, methylene C—H = 0.97 Å and methyl C—H = 0.96 Å. The displacement parameters were set for phenyl, methylene and aliphatic H atoms at Uiso(H)=1.2Ueq(C) or 1.5eq(methyl C).

Figures

Fig. 1.
The molecular structure of title compound, showing 50% probability displacement ellipsoids.

Crystal data

C21H20Cl3NO2F(000) = 880
Mr = 424.73Dx = 1.432 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 5467 reflections
a = 11.6295 (4) Åθ = 2.1–25.0°
b = 9.6955 (3) ŵ = 0.48 mm1
c = 17.4743 (5) ÅT = 293 K
β = 90.481 (1)°Prism, colourless
V = 1970.22 (11) Å30.22 × 0.16 × 0.16 mm
Z = 4

Data collection

Bruker Kappa APEXII CCD diffractometer6864 independent reflections
Radiation source: fine-focus sealed tube4998 reflections with I > 2σ(I)
graphiteRint = 0.023
ω and [var phi] scanθmax = 32.1°, θmin = 2.1°
Absorption correction: multi-scan (Blessing, 1995)h = −17→17
Tmin = 0.901, Tmax = 0.927k = −14→14
27536 measured reflectionsl = −26→26

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.045Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.141H-atom parameters constrained
S = 1.01w = 1/[σ2(Fo2) + (0.0727P)2 + 0.5226P] where P = (Fo2 + 2Fc2)/3
6864 reflections(Δ/σ)max = 0.001
244 parametersΔρmax = 0.40 e Å3
0 restraintsΔρmin = −0.31 e Å3

Special details

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)

xyzUiso*/Ueq
C10.85514 (12)0.37161 (13)−0.00740 (8)0.0341 (3)
H1A0.87460.4692−0.00040.041*
C20.96025 (12)0.30363 (15)−0.04343 (8)0.0385 (3)
H2A1.02370.3032−0.00620.046*
C30.93368 (13)0.15720 (15)−0.06701 (9)0.0415 (3)
C40.80789 (13)0.11575 (13)−0.07058 (8)0.0368 (3)
H4A0.78390.0981−0.01780.044*
C50.73061 (12)0.23387 (13)−0.10157 (7)0.0340 (2)
H5A0.74560.2437−0.15640.041*
C60.82292 (12)0.31664 (14)0.07135 (7)0.0346 (3)
C70.73896 (13)0.37879 (15)0.11624 (8)0.0393 (3)
C80.70953 (16)0.32934 (19)0.18766 (9)0.0505 (4)
H8A0.65190.37240.21550.061*
C90.76589 (18)0.2157 (2)0.21762 (9)0.0562 (4)
H9A0.74570.18100.26530.067*
C100.85181 (17)0.15487 (18)0.17638 (10)0.0529 (4)
H10A0.89110.07940.19650.063*
C110.88047 (14)0.20513 (16)0.10491 (9)0.0432 (3)
H11A0.94000.16330.07830.052*
C120.99879 (15)0.37953 (19)−0.11617 (10)0.0494 (4)
H12A1.06470.3339−0.13710.074*
H12B1.01840.4731−0.10360.074*
H12C0.93730.3790−0.15320.074*
C130.79149 (17)−0.01856 (16)−0.11449 (11)0.0516 (4)
H13A0.8409−0.0882−0.09310.077*
H13B0.8104−0.0044−0.16730.077*
H13C0.7129−0.0478−0.11080.077*
C140.60451 (13)0.19672 (14)−0.09241 (8)0.0380 (3)
C150.53718 (15)0.14574 (17)−0.15177 (10)0.0491 (4)
C160.42350 (17)0.1070 (2)−0.14119 (13)0.0619 (5)
H16A0.38090.0702−0.18160.074*
C170.37424 (16)0.12352 (19)−0.07036 (14)0.0614 (5)
H17A0.29780.0989−0.06300.074*
C180.43777 (16)0.17623 (19)−0.01064 (12)0.0548 (4)
H18A0.40410.18890.03690.066*
C190.55201 (14)0.21042 (16)−0.02132 (9)0.0432 (3)
H19A0.59490.24340.01990.052*
C200.73202 (12)0.49115 (14)−0.09783 (8)0.0379 (3)
C210.63849 (16)0.48474 (18)−0.15890 (10)0.0514 (4)
H21A0.57010.4434−0.13740.062*
H21B0.66400.4265−0.20060.062*
O11.01004 (12)0.07846 (14)−0.08337 (10)0.0692 (4)
O20.77569 (11)0.59995 (11)−0.07971 (7)0.0528 (3)
N10.75946 (10)0.36719 (11)−0.06397 (6)0.0326 (2)
Cl10.66924 (4)0.52622 (4)0.08431 (3)0.05574 (13)
Cl20.59251 (5)0.13268 (7)−0.24418 (3)0.07505 (18)
Cl30.60408 (4)0.64954 (5)−0.19502 (3)0.06205 (14)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0384 (6)0.0286 (6)0.0353 (6)0.0014 (5)−0.0026 (5)0.0020 (4)
C20.0353 (6)0.0382 (7)0.0421 (7)0.0015 (5)0.0007 (5)0.0047 (5)
C30.0434 (7)0.0362 (7)0.0452 (7)0.0071 (6)0.0061 (6)0.0042 (5)
C40.0440 (7)0.0285 (6)0.0379 (6)0.0028 (5)0.0056 (5)−0.0003 (5)
C50.0386 (6)0.0313 (6)0.0320 (6)0.0013 (5)0.0025 (5)−0.0023 (4)
C60.0407 (6)0.0305 (6)0.0325 (6)0.0025 (5)−0.0022 (5)−0.0009 (5)
C70.0441 (7)0.0364 (6)0.0373 (6)0.0048 (5)−0.0030 (5)−0.0051 (5)
C80.0543 (9)0.0583 (9)0.0390 (7)0.0055 (7)0.0056 (7)−0.0077 (7)
C90.0723 (11)0.0619 (10)0.0345 (7)0.0008 (9)0.0044 (7)0.0058 (7)
C100.0677 (11)0.0490 (9)0.0419 (8)0.0094 (8)−0.0027 (7)0.0106 (6)
C110.0509 (8)0.0402 (7)0.0386 (7)0.0104 (6)−0.0005 (6)0.0041 (6)
C120.0462 (8)0.0539 (9)0.0482 (8)−0.0054 (7)0.0069 (7)0.0089 (7)
C130.0646 (10)0.0333 (7)0.0571 (9)0.0017 (7)0.0077 (8)−0.0078 (6)
C140.0404 (7)0.0328 (6)0.0410 (7)−0.0012 (5)0.0011 (5)−0.0040 (5)
C150.0493 (8)0.0474 (8)0.0504 (8)−0.0004 (7)−0.0060 (7)−0.0089 (7)
C160.0525 (10)0.0523 (10)0.0804 (13)−0.0082 (8)−0.0200 (9)−0.0034 (9)
C170.0431 (9)0.0483 (9)0.0929 (15)−0.0075 (7)0.0031 (9)0.0139 (9)
C180.0503 (9)0.0458 (8)0.0686 (11)−0.0028 (7)0.0156 (8)0.0093 (8)
C190.0464 (8)0.0377 (7)0.0455 (7)−0.0033 (6)0.0074 (6)−0.0003 (6)
C200.0412 (7)0.0346 (6)0.0379 (6)0.0049 (5)0.0015 (5)0.0057 (5)
C210.0559 (9)0.0466 (8)0.0516 (9)0.0061 (7)−0.0126 (7)0.0126 (7)
O10.0535 (7)0.0504 (7)0.1039 (12)0.0162 (6)0.0167 (7)−0.0077 (7)
O20.0664 (8)0.0322 (5)0.0596 (7)−0.0005 (5)−0.0111 (6)0.0084 (5)
N10.0375 (5)0.0277 (5)0.0325 (5)0.0015 (4)−0.0017 (4)0.0018 (4)
Cl10.0653 (3)0.0465 (2)0.0555 (2)0.02331 (18)0.00334 (19)−0.00359 (17)
Cl20.0761 (3)0.1018 (4)0.0471 (2)0.0034 (3)−0.0109 (2)−0.0279 (2)
Cl30.0654 (3)0.0601 (3)0.0607 (3)0.0222 (2)−0.0028 (2)0.0202 (2)

Geometric parameters (Å, °)

C1—N11.4828 (17)C11—H11A0.9300
C1—C61.5253 (18)C12—H12A0.9600
C1—C21.5291 (19)C12—H12B0.9600
C1—H1A0.9800C12—H12C0.9600
C2—C31.510 (2)C13—H13A0.9600
C2—C121.539 (2)C13—H13B0.9600
C2—H2A0.9800C13—H13C0.9600
C3—O11.2072 (18)C14—C151.386 (2)
C3—C41.518 (2)C14—C191.395 (2)
C4—C131.523 (2)C15—C161.388 (3)
C4—C51.5506 (19)C15—Cl21.7480 (19)
C4—H4A0.9800C16—C171.378 (3)
C5—N11.4871 (17)C16—H16A0.9300
C5—C141.520 (2)C17—C181.372 (3)
C5—H5A0.9800C17—H17A0.9300
C6—C71.3946 (19)C18—C191.383 (2)
C6—C111.3979 (19)C18—H18A0.9300
C7—C81.383 (2)C19—H19A0.9300
C7—Cl11.7333 (15)C20—O21.2117 (19)
C8—C91.382 (3)C20—N11.3760 (16)
C8—H8A0.9300C20—C211.519 (2)
C9—C101.370 (3)C21—Cl31.7628 (16)
C9—H9A0.9300C21—H21A0.9700
C10—C111.384 (2)C21—H21B0.9700
C10—H10A0.9300
N1—C1—C6113.75 (11)C6—C11—H11A118.9
N1—C1—C2108.12 (11)C2—C12—H12A109.5
C6—C1—C2115.10 (11)C2—C12—H12B109.5
N1—C1—H1A106.4H12A—C12—H12B109.5
C6—C1—H1A106.4C2—C12—H12C109.5
C2—C1—H1A106.4H12A—C12—H12C109.5
C3—C2—C1110.81 (12)H12B—C12—H12C109.5
C3—C2—C12106.54 (13)C4—C13—H13A109.5
C1—C2—C12111.93 (12)C4—C13—H13B109.5
C3—C2—H2A109.2H13A—C13—H13B109.5
C1—C2—H2A109.2C4—C13—H13C109.5
C12—C2—H2A109.2H13A—C13—H13C109.5
O1—C3—C2120.67 (15)H13B—C13—H13C109.5
O1—C3—C4122.25 (15)C15—C14—C19116.86 (14)
C2—C3—C4117.08 (12)C15—C14—C5123.05 (13)
C3—C4—C13111.32 (13)C19—C14—C5120.08 (13)
C3—C4—C5111.98 (11)C14—C15—C16121.98 (17)
C13—C4—C5112.70 (13)C14—C15—Cl2120.50 (13)
C3—C4—H4A106.8C16—C15—Cl2117.50 (14)
C13—C4—H4A106.8C17—C16—C15119.46 (18)
C5—C4—H4A106.8C17—C16—H16A120.3
N1—C5—C14111.94 (10)C15—C16—H16A120.3
N1—C5—C4111.08 (11)C18—C17—C16120.09 (17)
C14—C5—C4110.19 (11)C18—C17—H17A120.0
N1—C5—H5A107.8C16—C17—H17A120.0
C14—C5—H5A107.8C17—C18—C19119.88 (18)
C4—C5—H5A107.8C17—C18—H18A120.1
C7—C6—C11115.67 (13)C19—C18—H18A120.1
C7—C6—C1122.34 (12)C18—C19—C14121.68 (16)
C11—C6—C1121.90 (12)C18—C19—H19A119.2
C8—C7—C6122.53 (14)C14—C19—H19A119.2
C8—C7—Cl1117.25 (12)O2—C20—N1123.57 (13)
C6—C7—Cl1120.20 (11)O2—C20—C21121.02 (13)
C9—C8—C7119.87 (15)N1—C20—C21115.37 (13)
C9—C8—H8A120.1C20—C21—Cl3111.94 (12)
C7—C8—H8A120.1C20—C21—H21A109.2
C10—C9—C8119.31 (15)Cl3—C21—H21A109.2
C10—C9—H9A120.3C20—C21—H21B109.2
C8—C9—H9A120.3Cl3—C21—H21B109.2
C9—C10—C11120.33 (16)H21A—C21—H21B107.9
C9—C10—H10A119.8C20—N1—C1115.56 (11)
C11—C10—H10A119.8C20—N1—C5121.24 (11)
C10—C11—C6122.20 (15)C1—N1—C5119.01 (10)
C10—C11—H11A118.9
N1—C1—C2—C3−58.03 (14)C1—C6—C11—C10179.89 (15)
C6—C1—C2—C370.37 (15)N1—C5—C14—C15136.19 (14)
N1—C1—C2—C1260.74 (15)C4—C5—C14—C15−99.67 (16)
C6—C1—C2—C12−170.85 (12)N1—C5—C14—C19−45.29 (17)
C1—C2—C3—O1−166.27 (15)C4—C5—C14—C1978.86 (16)
C12—C2—C3—O171.75 (19)C19—C14—C15—C16−1.4 (2)
C1—C2—C3—C414.92 (17)C5—C14—C15—C16177.20 (16)
C12—C2—C3—C4−107.06 (14)C19—C14—C15—Cl2176.79 (12)
O1—C3—C4—C13−13.9 (2)C5—C14—C15—Cl2−4.6 (2)
C2—C3—C4—C13164.91 (13)C14—C15—C16—C172.2 (3)
O1—C3—C4—C5−141.05 (16)Cl2—C15—C16—C17−176.06 (15)
C2—C3—C4—C537.74 (17)C15—C16—C17—C18−0.8 (3)
C3—C4—C5—N1−46.40 (15)C16—C17—C18—C19−1.2 (3)
C13—C4—C5—N1−172.84 (12)C17—C18—C19—C142.0 (3)
C3—C4—C5—C14−171.04 (11)C15—C14—C19—C18−0.7 (2)
C13—C4—C5—C1462.52 (15)C5—C14—C19—C18−179.31 (14)
N1—C1—C6—C7−62.84 (17)O2—C20—C21—Cl3−1.2 (2)
C2—C1—C6—C7171.62 (13)N1—C20—C21—Cl3176.76 (11)
N1—C1—C6—C11120.85 (14)O2—C20—N1—C1−5.4 (2)
C2—C1—C6—C11−4.69 (19)C21—C20—N1—C1176.75 (13)
C11—C6—C7—C8−3.4 (2)O2—C20—N1—C5−162.10 (14)
C1—C6—C7—C8−179.97 (14)C21—C20—N1—C520.01 (19)
C11—C6—C7—Cl1174.97 (12)C6—C1—N1—C20123.99 (12)
C1—C6—C7—Cl1−1.55 (19)C2—C1—N1—C20−106.85 (13)
C6—C7—C8—C91.4 (3)C6—C1—N1—C5−78.72 (14)
Cl1—C7—C8—C9−177.11 (14)C2—C1—N1—C550.45 (14)
C7—C8—C9—C101.0 (3)C14—C5—N1—C20−78.22 (15)
C8—C9—C10—C11−1.1 (3)C4—C5—N1—C20158.14 (12)
C9—C10—C11—C6−1.2 (3)C14—C5—N1—C1125.81 (12)
C7—C6—C11—C103.4 (2)C4—C5—N1—C12.17 (16)

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: EZ2226).

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