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Acta Crystallogr Sect E Struct Rep Online. 2010 June 1; 66(Pt 6): o1479.
Published online 2010 May 29. doi:  10.1107/S160053681001901X
PMCID: PMC2979607

1-(2-Bromo­acet­yl)-3-methyl-2,6-diphenyl­piperidin-4-one

Abstract

In the title compound, C20H20BrNO2, the piperidone ring adopts a boat conformation. The phenyl rings are oriented at dihedral angles of 97.8 (2) and 96.0 (1)° with respect to the best plane through the piperidine ring. The dihedral angle between the two phenyl rings is 49.7 (1)°. In the crystal, bifurcated C—H(...)O hydrogen bonds form a R 2 1(7) ring motif, linking the mol­ecules into centrosymmetric dimers.

Related literature

For the biological activity of functionalized piperidines, see: Richardo et al. (1979 [triangle]); Schneider (1996 [triangle]); Mukhtar & Wright (2005 [triangle]); Aridoss et al. (2007 [triangle]); Winkler & Holan (1989 [triangle]). For related structures see: Aridoss et al. (2009a [triangle],b [triangle]). For ring conformational analysis, see: Cremer & Pople (1975 [triangle]); Nardelli (1983 [triangle]).

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Object name is e-66-o1479-scheme1.jpg

Experimental

Crystal data

  • C20H20BrNO2
  • M r = 386.28
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o1479-efi1.jpg
  • a = 21.4006 (8) Å
  • b = 14.5873 (6) Å
  • c = 13.8107 (5) Å
  • β = 125.368 (2)°
  • V = 3515.7 (2) Å3
  • Z = 8
  • Mo Kα radiation
  • μ = 2.35 mm−1
  • T = 292 K
  • 0.3 × 0.26 × 0.22 mm

Data collection

  • Bruker SMART APEXII area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2008 [triangle]) T min = 0.499, T max = 0.596
  • 17094 measured reflections
  • 4398 independent reflections
  • 2725 reflections with I > 2σ(I)
  • R int = 0.035

Refinement

  • R[F 2 > 2σ(F 2)] = 0.059
  • wR(F 2) = 0.213
  • S = 1.02
  • 4398 reflections
  • 218 parameters
  • H-atom parameters constrained
  • Δρmax = 0.53 e Å−3
  • Δρmin = −0.77 e Å−3

Data collection: APEX2 (Bruker, 2008 [triangle]); cell refinement: SAINT (Bruker, 2008 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [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 and PLATON (Spek, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053681001901X/bt5275sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S160053681001901X/bt5275Isup2.hkl

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

Acknowledgments

GA and YTJ are grateful for the support provided by the second stage of the BK21 program, Republic of Korea. SS and DV thank the TBI X-ray Facility, CAS in Crystallography and Biophysics, University of Madras, India, for the data collection and the University Grants Commission (UGC&SAP) for financial support.

supplementary crystallographic information

Comment

Amides are prominent functional groups in chemistry due to their integral part in biologically important polymers such as peptides and proteins. Functionalized piperidines are among the most common building blocks in natural products and more interestingly, in many biologically active compounds such as anopterine, pergoline, scopolamine and morphine (Richardo et al., 1979, Schneider, 1996, Mukhtar & Wright, 2005). Piperidones also have high impact in medicinal field owing to their role as key chiral intermediates for the preparation of a variety of natural, synthetic and semi-synthetic pharmacophores with marked anticancer and anti-HIV activities (Winkler & Holan, 1989). It has been established by our earlier studies (Aridoss et al. 2009a, Aridoss et al. 2009b) that unlike the substitution of either alky or aryl system in the carbon skeleton of piperidone, incorporation of either chloroacetyl or bromoacetyl functionality at the nitrogen of piperidone remarkably changes the rigid chair confirmation of heterocyclic ring into non-chair conformation of its preference. Thus to find out the change in conformation of 2,6-diphenyl-3-methylpiperidin-4-one upon bromoacetylation, the title compound was synthesized and discussed here with its X-ray crystallographic data.

In the present structure, the piperidone ring adopts a boat conformation with atoms C1 and C4 deviating by 0.395 (1) and 0.334 (1) Å, respectively, from the least-sqaures plane defined by the remaining atoms (N1/C2/C3/C5) in the ring. When compared with the reported structures of piperidone derivatives (Aridoss et al., 2009b), it is clear that the conformation of the piperidone ring is highly influenced by the substitutions at various positions.The sum of the bond angles around the atom N1(357.6 (6)°) of the piperidone ring in the molecule is in accordance with sp2 hybridization.

The puckering parameters (Cremer & Pople,1975) and the smallest displacement asymmetry parameters (Nardelli, 1983) for piperidone ring are q2 = 0.639 (4) Å, q3 = 0.062 (1) Å; QT = 0.642 (4) Å and [var phi]2 = 84.4 (1) °, respectively. Atoms C2 and C13 act as donors to form bifurcated hydrogen bonds with atom O1' as an aceptor. In the crystal structure, the molecules at (x,y,z) and (-x,-y-1, -z ) are linked by C2—H2A···O1' hydrogen bonds into cyclic centrosymmetric R22(8) dimer.

Experimental

The title compound was obtained by adopting our earlier method (Aridoss et al. 2007). To a solution of 2,6-diphenyl-3-methylpiperidin -4-one (1 equiv.) and NEt3 (1.5 equiv.) in freshly distilled benzene, bromoacetyl chloride (1 equiv.) in benzene was added in drop wise. After the completion of reaction, the crude compound was obtained by evaporation of its ethyl acetate extract. This upon recrystallization in distilled ethanol afforded fine white crystals suitable for X-ray diffraction study.

Refinement

H atoms were positioned geometrically (C—H=0.93-0.98Å) and allowed to ride on their parent atoms, with 1.5Ueq(C) for methyl H and 1.2 Ueq(C) for other H atoms.

Figures

Fig. 1.
Perspective view of the molecule showing the thermal ellipsoids are drawn at 30% probability level.
Fig. 2.
Crystal packing showing the formation of ring R21(7) Bifurcated and the centrosymmetric R22(8) dimer. For the clarity, H atoms are deleted which are not involved in the bond formation.

Crystal data

C20H20BrNO2F(000) = 1584
Mr = 386.28Dx = 1.460 Mg m3
Monoclinic, C2/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2ycCell parameters from 2025 reflections
a = 21.4006 (8) Åθ = 0.5–0.6°
b = 14.5873 (6) ŵ = 2.35 mm1
c = 13.8107 (5) ÅT = 292 K
β = 125.368 (2)°Block, colorless
V = 3515.7 (2) Å30.3 × 0.26 × 0.22 mm
Z = 8

Data collection

Bruker SMART APEXII area-detector diffractometer4398 independent reflections
Radiation source: fine-focus sealed tube2725 reflections with I > 2σ(I)
graphiteRint = 0.035
ω and [var phi] scansθmax = 28.5°, θmin = 1.8°
Absorption correction: multi-scan (SADABS; Bruker, 2008)h = −27→28
Tmin = 0.499, Tmax = 0.596k = −19→19
17094 measured reflectionsl = −18→18

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)] = 0.059Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.213H-atom parameters constrained
S = 1.02w = 1/[σ2(Fo2) + (0.1259P)2 + 4.1414P] where P = (Fo2 + 2Fc2)/3
4398 reflections(Δ/σ)max < 0.001
218 parametersΔρmax = 0.53 e Å3
0 restraintsΔρmin = −0.77 e Å3

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. 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
C10.00908 (18)0.2545 (2)0.0494 (3)0.0355 (7)
H10.05550.23170.12290.043*
C20.0317 (2)0.3418 (3)0.0168 (4)0.0517 (10)
H2A0.04320.38890.07450.062*
H2B0.07800.33030.02140.062*
C3−0.0287 (3)0.3764 (3)−0.1039 (4)0.0581 (11)
C4−0.0933 (2)0.3111 (3)−0.1867 (3)0.0463 (8)
H4−0.13070.3148−0.16740.056*
C5−0.06703 (18)0.2104 (2)−0.1692 (3)0.0359 (7)
H5−0.03930.2039−0.20560.043*
C6−0.13640 (19)0.1469 (2)−0.2373 (3)0.0355 (7)
C7−0.1502 (2)0.0969 (3)−0.3328 (3)0.0502 (9)
H7−0.11500.0987−0.35180.060*
C8−0.2159 (3)0.0440 (3)−0.4008 (3)0.0605 (11)
H8−0.22490.0115−0.46570.073*
C9−0.2672 (2)0.0396 (3)−0.3726 (4)0.0622 (12)
H9−0.31100.0038−0.41790.075*
C10−0.2541 (2)0.0881 (3)−0.2772 (4)0.0526 (10)
H10−0.28910.0848−0.25770.063*
C11−0.1889 (2)0.1421 (2)−0.2096 (3)0.0408 (8)
H11−0.18050.1752−0.14550.049*
C12−0.05143 (17)0.2656 (2)0.0741 (3)0.0334 (7)
C13−0.0720 (2)0.3505 (2)0.0908 (4)0.0470 (9)
H13−0.05100.40340.08310.056*
C14−0.1253 (3)0.3567 (3)0.1196 (4)0.0584 (11)
H14−0.13880.41400.13150.070*
C15−0.1573 (2)0.2800 (3)0.1301 (4)0.0566 (11)
H15−0.19340.28500.14690.068*
C16−0.1354 (2)0.1944 (3)0.1156 (3)0.0508 (9)
H16−0.15660.14170.12330.061*
C17−0.0820 (2)0.1873 (3)0.0896 (3)0.0408 (8)
H17−0.06650.12970.08250.049*
C18−0.1349 (3)0.3390 (3)−0.3166 (5)0.0706 (14)
H18A−0.14950.4023−0.32550.106*
H18B−0.18000.3019−0.36480.106*
H18C−0.10160.3302−0.34120.106*
C190.02886 (17)0.1079 (2)−0.0205 (3)0.0353 (7)
C200.09463 (19)0.0844 (3)0.1063 (3)0.0432 (8)
H20A0.10630.01950.11250.052*
H20B0.08030.09820.15980.052*
N1−0.01254 (14)0.18526 (19)−0.0422 (2)0.0328 (6)
O1−0.0265 (3)0.4523 (2)−0.1361 (4)0.1037 (15)
O20.01584 (14)0.05669 (18)−0.1000 (2)0.0472 (6)
Br10.18249 (2)0.15486 (4)0.14906 (5)0.0736 (3)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0316 (14)0.0321 (16)0.0404 (17)−0.0039 (12)0.0195 (13)−0.0042 (13)
C20.048 (2)0.040 (2)0.076 (3)−0.0124 (15)0.041 (2)−0.0081 (18)
C30.080 (3)0.041 (2)0.074 (3)−0.008 (2)0.056 (3)0.003 (2)
C40.050 (2)0.0399 (19)0.055 (2)0.0067 (16)0.0333 (18)0.0140 (17)
C50.0375 (16)0.0403 (18)0.0344 (16)0.0051 (13)0.0234 (14)0.0063 (14)
C60.0326 (15)0.0386 (17)0.0287 (14)0.0096 (12)0.0140 (13)0.0056 (13)
C70.051 (2)0.059 (2)0.0373 (18)0.0107 (18)0.0239 (17)0.0013 (17)
C80.059 (2)0.061 (3)0.0353 (18)0.009 (2)0.0120 (17)−0.0110 (18)
C90.042 (2)0.058 (3)0.050 (2)−0.0027 (18)0.0060 (17)−0.011 (2)
C100.0347 (18)0.061 (3)0.054 (2)0.0003 (16)0.0205 (16)−0.0042 (19)
C110.0352 (16)0.046 (2)0.0372 (17)0.0049 (14)0.0187 (14)−0.0013 (15)
C120.0284 (13)0.0383 (17)0.0270 (14)−0.0006 (12)0.0124 (12)−0.0013 (13)
C130.053 (2)0.0346 (18)0.054 (2)0.0059 (15)0.0313 (19)0.0036 (16)
C140.066 (3)0.057 (3)0.064 (3)0.021 (2)0.044 (2)0.007 (2)
C150.043 (2)0.086 (3)0.046 (2)0.013 (2)0.0288 (17)0.009 (2)
C160.047 (2)0.064 (2)0.0411 (19)−0.0131 (19)0.0259 (17)−0.0015 (18)
C170.0459 (19)0.0381 (18)0.0377 (17)−0.0052 (15)0.0237 (15)−0.0045 (15)
C180.077 (3)0.066 (3)0.063 (3)0.011 (2)0.037 (3)0.030 (2)
C190.0279 (14)0.0363 (17)0.0400 (17)0.0017 (12)0.0187 (13)0.0006 (14)
C200.0322 (15)0.0412 (19)0.0468 (19)0.0022 (13)0.0175 (14)0.0030 (15)
N10.0313 (13)0.0331 (13)0.0329 (13)0.0013 (10)0.0179 (11)−0.0002 (11)
O10.161 (4)0.047 (2)0.096 (3)−0.030 (2)0.071 (3)0.0106 (18)
O20.0424 (13)0.0498 (15)0.0456 (14)0.0084 (11)0.0233 (11)−0.0064 (12)
Br10.0406 (3)0.0898 (5)0.0780 (4)−0.0045 (2)0.0272 (3)−0.0027 (3)

Geometric parameters (Å, °)

C1—N11.468 (4)C10—C111.391 (5)
C1—C21.521 (5)C10—H100.9300
C1—C121.527 (4)C11—H110.9300
C1—H10.9800C12—C131.378 (5)
C2—C31.486 (7)C12—C171.394 (5)
C2—H2A0.9700C13—C141.411 (6)
C2—H2B0.9700C13—H130.9300
C3—O11.204 (5)C14—C151.362 (7)
C3—C41.516 (6)C14—H140.9300
C4—C181.525 (6)C15—C161.389 (6)
C4—C51.541 (5)C15—H150.9300
C4—H40.9800C16—C171.384 (5)
C5—N11.485 (4)C16—H160.9300
C5—C61.527 (5)C17—H170.9300
C5—H50.9800C18—H18A0.9600
C6—C71.382 (5)C18—H18B0.9600
C6—C111.381 (5)C18—H18C0.9600
C7—C81.387 (6)C19—O21.219 (4)
C7—H70.9300C19—N11.357 (4)
C8—C91.362 (7)C19—C201.520 (5)
C8—H80.9300C20—Br11.912 (4)
C9—C101.375 (6)C20—H20A0.9700
C9—H90.9300C20—H20B0.9700
N1—C1—C2108.5 (3)C11—C10—H10119.9
N1—C1—C12112.4 (2)C6—C11—C10120.3 (3)
C2—C1—C12115.7 (3)C6—C11—H11119.8
N1—C1—H1106.6C10—C11—H11119.8
C2—C1—H1106.6C13—C12—C17119.2 (3)
C12—C1—H1106.6C13—C12—C1121.9 (3)
C3—C2—C1113.4 (3)C17—C12—C1118.8 (3)
C3—C2—H2A108.9C12—C13—C14119.5 (4)
C1—C2—H2A108.9C12—C13—H13120.2
C3—C2—H2B108.9C14—C13—H13120.2
C1—C2—H2B108.9C15—C14—C13121.0 (4)
H2A—C2—H2B107.7C15—C14—H14119.5
O1—C3—C2122.2 (5)C13—C14—H14119.5
O1—C3—C4120.8 (5)C14—C15—C16119.4 (4)
C2—C3—C4117.0 (3)C14—C15—H15120.3
C3—C4—C18112.1 (3)C16—C15—H15120.3
C3—C4—C5112.9 (3)C17—C16—C15120.2 (4)
C18—C4—C5110.5 (3)C17—C16—H16119.9
C3—C4—H4107.0C15—C16—H16119.9
C18—C4—H4107.0C16—C17—C12120.6 (4)
C5—C4—H4107.0C16—C17—H17119.7
N1—C5—C6113.4 (3)C12—C17—H17119.7
N1—C5—C4112.7 (3)C4—C18—H18A109.5
C6—C5—C4110.2 (3)C4—C18—H18B109.5
N1—C5—H5106.7H18A—C18—H18B109.5
C6—C5—H5106.7C4—C18—H18C109.5
C4—C5—H5106.7H18A—C18—H18C109.5
C7—C6—C11118.6 (3)H18B—C18—H18C109.5
C7—C6—C5120.2 (3)O2—C19—N1122.1 (3)
C11—C6—C5121.1 (3)O2—C19—C20118.4 (3)
C6—C7—C8120.8 (4)N1—C19—C20119.5 (3)
C6—C7—H7119.6C19—C20—Br1108.9 (2)
C8—C7—H7119.6C19—C20—H20A109.9
C9—C8—C7120.1 (4)Br1—C20—H20A109.9
C9—C8—H8120.0C19—C20—H20B109.9
C7—C8—H8120.0Br1—C20—H20B109.9
C8—C9—C10120.0 (4)H20A—C20—H20B108.3
C8—C9—H9120.0C19—N1—C1122.8 (3)
C10—C9—H9120.0C19—N1—C5115.6 (3)
C9—C10—C11120.1 (4)C1—N1—C5119.2 (3)
C9—C10—H10119.9
N1—C1—C2—C355.3 (4)C2—C1—C12—C13−13.3 (5)
C12—C1—C2—C3−72.0 (4)N1—C1—C12—C1746.6 (4)
C1—C2—C3—O1166.4 (5)C2—C1—C12—C17172.0 (3)
C1—C2—C3—C4−14.4 (5)C17—C12—C13—C14−1.9 (5)
O1—C3—C4—C1819.2 (6)C1—C12—C13—C14−176.7 (3)
C2—C3—C4—C18−159.9 (4)C12—C13—C14—C15−0.6 (7)
O1—C3—C4—C5144.8 (5)C13—C14—C15—C161.8 (7)
C2—C3—C4—C5−34.4 (5)C14—C15—C16—C17−0.5 (6)
C3—C4—C5—N141.5 (4)C15—C16—C17—C12−2.0 (5)
C18—C4—C5—N1167.9 (3)C13—C12—C17—C163.2 (5)
C3—C4—C5—C6169.2 (3)C1—C12—C17—C16178.1 (3)
C18—C4—C5—C6−64.3 (4)O2—C19—C20—Br198.6 (3)
N1—C5—C6—C7−119.1 (3)N1—C19—C20—Br1−80.3 (3)
C4—C5—C6—C7113.5 (3)O2—C19—N1—C1−170.7 (3)
N1—C5—C6—C1164.7 (4)C20—C19—N1—C18.1 (5)
C4—C5—C6—C11−62.7 (4)O2—C19—N1—C5−8.3 (5)
C11—C6—C7—C80.9 (5)C20—C19—N1—C5170.5 (3)
C5—C6—C7—C8−175.3 (3)C2—C1—N1—C19113.0 (3)
C6—C7—C8—C9−1.1 (6)C12—C1—N1—C19−117.8 (3)
C7—C8—C9—C100.4 (7)C2—C1—N1—C5−48.8 (4)
C8—C9—C10—C110.4 (6)C12—C1—N1—C580.3 (3)
C7—C6—C11—C10−0.1 (5)C6—C5—N1—C1971.5 (3)
C5—C6—C11—C10176.1 (3)C4—C5—N1—C19−162.4 (3)
C9—C10—C11—C6−0.5 (6)C6—C5—N1—C1−125.4 (3)
N1—C1—C12—C13−138.6 (3)C4—C5—N1—C10.7 (4)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C2—H2A···O1i0.972.563.458 (6)154
C13—H13···O1i0.932.513.404 (5)161

Symmetry codes: (i) −x, −y+1, −z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BT5275).

References

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