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Acta Crystallogr Sect E Struct Rep Online. 2009 November 1; 65(Pt 11): o2818.
Published online 2009 October 23. doi:  10.1107/S1600536809041609
PMCID: PMC2971115

1-Formyl-r-2,c-6-bis­(4-methoxy­phen­yl)-t-3,t-5-dimethyl­piperidin-4-one

Abstract

In the title compound, C22H25NO4, the piperidine ring adopts a distorted boat conformation. The methyl groups at the 3 and 5 positions of the piperidine ring are in axial and equatorial orientations, respectively. Both H and O atoms in the aldehyde group are disordered over two positions with occupancies of 0.534 (5) and 0.466 (5). In the crystal, the mol­ecules are linked into a three-dimensional network by C—H(...)O hydrogen bonds.

Related literature

For general background to piperidine derivatives, see: Escolano & Amat (2006 [triangle]); Wang & Wuorola (1992 [triangle]); Grishina et al. (1994 [triangle]). For hydrogen-bond motifs, see: Bernstein et al. (1995 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o2818-scheme1.jpg

Experimental

Crystal data

  • C22H25NO4
  • M r = 367.43
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o2818-efi1.jpg
  • a = 11.0954 (4) Å
  • b = 14.5407 (3) Å
  • c = 12.7050 (4) Å
  • β = 110.977 (1)°
  • V = 1913.91 (10) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 293 K
  • 0.30 × 0.20 × 0.20 mm

Data collection

  • Bruker Kappa APEXII CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 2001 [triangle]) T min = 0.974, T max = 0.974
  • 24720 measured reflections
  • 5524 independent reflections
  • 3703 reflections with I > 2σ(I)
  • R int = 0.029

Refinement

  • R[F 2 > 2σ(F 2)] = 0.048
  • wR(F 2) = 0.140
  • S = 1.05
  • 5524 reflections
  • 256 parameters
  • H-atom parameters constrained
  • Δρmax = 0.23 e Å−3
  • Δρmin = −0.23 e Å−3

Data collection: APEX2 (Bruker, 2004 [triangle]); cell refinement: SAINT (Bruker, 2004 [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 I, global. DOI: 10.1107/S1600536809041609/ci2909sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809041609/ci2909Isup2.hkl

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

Acknowledgments

TK thanks Dr Babu Varghese, SAIF, IIT-Madras, Chennai, India, for his help with the data collection. SP thanks the UGC, India, for financial support.

supplementary crystallographic information

Comment

The piperidine ring is a common feature occurring in many biologically active natural products and therapeutic agents. Piperidine containing entities constitute important targets for pharmaceutical research (Escolano & Amat, 2006). Piperidine derivatives, namely 4-piperidones are synthetic intermediates in the preparation of various alkaloids and pharmaceutical products (Wang et al., 1992; Grishina et al., 1994).

In the title molecule (Fig.1), the piperidine ring adopts a distorted boat conformation. The methyl groups at 3 and 5 positions of the piperidine ring are in axial and equatorial orientations [N1—C2—C3—C14 = -63.02 (15)° and N1—C6—C5—C15 = 176.60 (11)°]. The phenyl rings at 2 and 6 positions of the piperidine ring are axially [C4—C3—C2—C8 = -68.32 (14)°] and equatorially [C4—C5—C6—C16 = 176.69 (10)°] oriented. The dihedral angle between the two phenyl rings is 41.97 (8)°.

Centrosymmetrically related molecules form R22(8) (Bernstein et al., 1995) dimers through C—H···O hydrogen bonds involving atoms C3 and O1. The dimers are linked into a zigzag C(8) chain running along the b axis by intermolecular C—H···O hydrogen bonds involving atoms C20 and O1 (Table 1). Further, C15—H15C···O2 interactions link the chains along the c axis to form a three-dimensional network.

Experimental

An ice-cold solution of acetic-formic anhydride was prepared from acetic anhydride (10 ml) and 85% formic acid (5 ml) and was added slowly to a cold solution of r-2,c-6-bis(4-methoxyphenyl)-t-3,t-5-dimethylpiperidin-4-one (1.69 g) in benzene (30 ml). The reaction mixture was stirred at room temperature for 5 h. The organic layer was separated, dried over anhydrous Na2SO4 and concentrated. The resulting mass was purified by crystallization from benzene-petroleum ether (333–353 K) in the ratio 1:1.

Refinement

The O and H atoms of the formyl group is disordered over two positions with occupancies of 0.534 (5) and 0.466 (5). H atoms were positioned geometrically (C-H = 0.93–0.98 Å) and allowed to ride on their parent atoms, with Uiso(H) = 1.5Ueq(Cmethyl) and 1.2Ueq(C). A rotating group model was used for the methoxy methyl groups.

Figures

Fig. 1.
The molecular structure of the title compound. Displacement ellipsoids are drawn at the 30% probability level. Both disorder components are shown. H atoms have been omitted for clarity.
Fig. 2.
The crystal packing of the title compound. H atoms not involved in hydrogen bonding (dashed lines) have been omitted.

Crystal data

C22H25NO4F(000) = 784
Mr = 367.43Dx = 1.275 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 5524 reflections
a = 11.0954 (4) Åθ = 2.1–29.9°
b = 14.5407 (3) ŵ = 0.09 mm1
c = 12.7050 (4) ÅT = 293 K
β = 110.977 (1)°Block, colourless
V = 1913.91 (10) Å30.30 × 0.20 × 0.20 mm
Z = 4

Data collection

Bruker Kappa APEXII CCD area-detector diffractometer5524 independent reflections
Radiation source: fine-focus sealed tube3703 reflections with I > 2σ(I)
graphiteRint = 0.029
ω and [var phi] scansθmax = 29.9°, θmin = 2.1°
Absorption correction: multi-scan (SADABS; Sheldrick, 2001)h = −15→12
Tmin = 0.974, Tmax = 0.974k = −20→19
24720 measured reflectionsl = −17→17

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)] = 0.048Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.140H-atom parameters constrained
S = 1.05w = 1/[σ2(Fo2) + (0.0598P)2 + 0.3189P] where P = (Fo2 + 2Fc2)/3
5524 reflections(Δ/σ)max = 0.001
256 parametersΔρmax = 0.23 e Å3
0 restraintsΔρmin = −0.23 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*/UeqOcc. (<1)
O10.87856 (11)0.03534 (7)0.05971 (10)0.0574 (3)
O21.0929 (3)0.3733 (2)0.3086 (2)0.1143 (15)0.534 (5)
O2'1.2050 (3)0.3881 (2)0.2198 (3)0.1036 (16)0.466 (5)
O30.92438 (12)0.33025 (8)−0.37580 (9)0.0647 (3)
O40.60958 (11)0.58982 (7)0.13202 (9)0.0600 (3)
N11.03399 (11)0.28962 (8)0.15129 (9)0.0446 (3)
C21.08936 (13)0.22990 (9)0.08641 (11)0.0433 (3)
H21.18310.23890.11770.052*
C31.06451 (13)0.13017 (10)0.10905 (12)0.0455 (3)
H31.09760.09060.06310.055*
C40.92172 (13)0.11238 (9)0.07622 (11)0.0408 (3)
C50.83662 (12)0.19522 (9)0.06811 (11)0.0397 (3)
H50.81820.2227−0.00640.048*
C60.90568 (13)0.26797 (9)0.15605 (10)0.0402 (3)
H60.91980.24150.23050.048*
C71.1102 (2)0.34871 (18)0.22651 (19)0.0930 (7)
H71.18150.37200.21330.112*0.534 (5)
H7'1.08870.36190.29180.112*0.466 (5)
C81.04508 (12)0.25691 (9)−0.03708 (11)0.0405 (3)
C91.01446 (16)0.19282 (10)−0.12353 (13)0.0536 (4)
H91.02000.1305−0.10620.064*
C100.97608 (17)0.21971 (11)−0.23422 (13)0.0582 (4)
H100.95540.1753−0.29060.070*
C110.96764 (14)0.31160 (10)−0.26313 (12)0.0472 (3)
C121.00016 (15)0.37652 (10)−0.17907 (13)0.0517 (4)
H120.99680.4387−0.19680.062*
C131.03795 (14)0.34869 (10)−0.06774 (13)0.0496 (3)
H131.05930.3932−0.01150.060*
C141.13194 (17)0.10344 (14)0.23312 (14)0.0675 (5)
H14A1.22190.11870.25680.101*
H14B1.12270.03850.24170.101*
H14C1.09340.13640.27860.101*
C150.70806 (15)0.16822 (11)0.07688 (17)0.0619 (4)
H15A0.65310.22130.06370.093*
H15B0.72240.14440.15090.093*
H15C0.66750.12190.02160.093*
C160.82499 (13)0.35393 (9)0.14503 (11)0.0406 (3)
C170.79081 (14)0.40931 (9)0.05079 (11)0.0435 (3)
H170.81740.3932−0.00840.052*
C180.71800 (14)0.48820 (9)0.04184 (11)0.0444 (3)
H180.69600.5246−0.02250.053*
C190.67825 (13)0.51235 (9)0.12957 (11)0.0433 (3)
C200.70878 (16)0.45640 (11)0.22319 (12)0.0533 (4)
H200.68030.47150.28150.064*
C210.78103 (16)0.37843 (10)0.23047 (12)0.0518 (4)
H210.80090.34130.29400.062*
C220.9119 (2)0.42401 (13)−0.40951 (16)0.0748 (5)
H22A0.87990.4276−0.49030.112*
H22B0.99460.4535−0.37970.112*
H22C0.85270.4543−0.38130.112*
C230.58744 (18)0.65403 (12)0.04332 (15)0.0655 (5)
H23A0.54420.70700.05780.098*
H23B0.53460.6263−0.02650.098*
H23C0.66850.67230.03860.098*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0733 (7)0.0333 (5)0.0769 (7)−0.0017 (5)0.0407 (6)−0.0034 (5)
O20.096 (2)0.140 (3)0.085 (2)0.0135 (19)0.0052 (15)−0.072 (2)
O2'0.0510 (18)0.085 (2)0.156 (3)−0.0229 (15)0.0140 (18)−0.046 (2)
O30.0798 (8)0.0614 (7)0.0550 (6)0.0062 (6)0.0265 (6)0.0104 (5)
O40.0746 (7)0.0486 (6)0.0589 (6)0.0254 (5)0.0266 (5)0.0045 (5)
N10.0411 (6)0.0452 (6)0.0437 (6)−0.0008 (5)0.0105 (5)−0.0090 (5)
C20.0353 (6)0.0446 (8)0.0507 (7)0.0034 (5)0.0162 (6)−0.0003 (6)
C30.0479 (8)0.0426 (8)0.0514 (8)0.0141 (6)0.0243 (6)0.0085 (6)
C40.0526 (8)0.0337 (7)0.0423 (7)0.0041 (6)0.0244 (6)0.0024 (5)
C50.0399 (6)0.0335 (6)0.0467 (7)0.0032 (5)0.0166 (5)0.0013 (5)
C60.0479 (7)0.0379 (7)0.0366 (6)0.0073 (6)0.0173 (5)0.0014 (5)
C70.0728 (13)0.1154 (18)0.0846 (14)−0.0275 (13)0.0205 (11)−0.0533 (13)
C80.0373 (6)0.0380 (7)0.0518 (7)0.0001 (5)0.0227 (6)0.0001 (6)
C90.0768 (11)0.0344 (7)0.0575 (9)0.0039 (7)0.0337 (8)0.0006 (6)
C100.0841 (12)0.0440 (8)0.0535 (9)0.0016 (8)0.0330 (8)−0.0051 (7)
C110.0452 (7)0.0494 (8)0.0525 (8)0.0033 (6)0.0242 (6)0.0044 (6)
C120.0569 (9)0.0368 (7)0.0652 (9)−0.0021 (6)0.0264 (7)0.0065 (7)
C130.0550 (8)0.0379 (7)0.0588 (8)−0.0072 (6)0.0237 (7)−0.0043 (6)
C140.0601 (10)0.0778 (12)0.0615 (10)0.0226 (9)0.0179 (8)0.0232 (9)
C150.0469 (8)0.0496 (9)0.0950 (13)0.0020 (7)0.0323 (8)−0.0004 (8)
C160.0500 (7)0.0346 (7)0.0385 (6)0.0058 (5)0.0175 (5)−0.0017 (5)
C170.0535 (8)0.0428 (7)0.0378 (6)0.0063 (6)0.0208 (6)−0.0009 (5)
C180.0526 (8)0.0398 (7)0.0402 (7)0.0050 (6)0.0159 (6)0.0042 (6)
C190.0473 (7)0.0361 (7)0.0460 (7)0.0059 (6)0.0160 (6)−0.0032 (5)
C200.0732 (10)0.0496 (9)0.0462 (8)0.0149 (7)0.0324 (7)0.0006 (6)
C210.0746 (10)0.0454 (8)0.0412 (7)0.0165 (7)0.0280 (7)0.0066 (6)
C220.0856 (13)0.0710 (12)0.0707 (11)0.0147 (10)0.0316 (10)0.0259 (9)
C230.0765 (11)0.0466 (9)0.0673 (10)0.0210 (8)0.0183 (9)0.0075 (8)

Geometric parameters (Å, °)

O1—C41.2067 (16)C10—C111.380 (2)
O2—C71.182 (3)C10—H100.93
O2'—C71.227 (4)C11—C121.373 (2)
O3—C111.3642 (18)C12—C131.384 (2)
O3—C221.421 (2)C12—H120.93
O4—C191.3665 (16)C13—H130.93
O4—C231.416 (2)C14—H14A0.96
N1—C71.337 (2)C14—H14B0.96
N1—C21.4743 (17)C14—H14C0.96
N1—C61.4803 (17)C15—H15A0.96
C2—C81.5183 (19)C15—H15B0.96
C2—C31.523 (2)C15—H15C0.96
C2—H20.98C16—C171.3787 (18)
C3—C41.509 (2)C16—C211.3865 (18)
C3—C141.533 (2)C17—C181.3840 (19)
C3—H30.98C17—H170.93
C4—C51.5111 (18)C18—C191.3829 (19)
C5—C151.521 (2)C18—H180.93
C5—C61.5302 (18)C19—C201.379 (2)
C5—H50.98C20—C211.372 (2)
C6—C161.5145 (18)C20—H200.93
C6—H60.98C21—H210.93
C7—H70.93C22—H22A0.96
C7—H7'0.96C22—H22B0.96
C8—C131.385 (2)C22—H22C0.96
C8—C91.387 (2)C23—H23A0.96
C9—C101.372 (2)C23—H23B0.96
C9—H90.93C23—H23C0.96
C11—O3—C22117.82 (13)C12—C11—C10118.99 (14)
C19—O4—C23117.70 (12)C11—C12—C13119.53 (14)
C7—N1—C2119.66 (14)C11—C12—H12120.2
C7—N1—C6118.59 (14)C13—C12—H12120.2
C2—N1—C6119.80 (10)C12—C13—C8122.36 (14)
N1—C2—C8112.33 (11)C12—C13—H13118.8
N1—C2—C3108.39 (11)C8—C13—H13118.8
C8—C2—C3115.34 (12)C3—C14—H14A109.5
N1—C2—H2106.8C3—C14—H14B109.5
C8—C2—H2106.8H14A—C14—H14B109.5
C3—C2—H2106.8C3—C14—H14C109.5
C4—C3—C2110.75 (11)H14A—C14—H14C109.5
C4—C3—C14108.56 (12)H14B—C14—H14C109.5
C2—C3—C14112.39 (13)C5—C15—H15A109.5
C4—C3—H3108.3C5—C15—H15B109.5
C2—C3—H3108.3H15A—C15—H15B109.5
C14—C3—H3108.3C5—C15—H15C109.5
O1—C4—C3121.28 (12)H15A—C15—H15C109.5
O1—C4—C5121.92 (13)H15B—C15—H15C109.5
C3—C4—C5116.79 (11)C17—C16—C21117.74 (12)
C4—C5—C15111.63 (11)C17—C16—C6122.14 (11)
C4—C5—C6111.35 (11)C21—C16—C6120.11 (12)
C15—C5—C6111.25 (12)C16—C17—C18121.77 (12)
C4—C5—H5107.5C16—C17—H17119.1
C15—C5—H5107.5C18—C17—H17119.1
C6—C5—H5107.5C19—C18—C17119.31 (12)
N1—C6—C16111.47 (11)C19—C18—H18120.3
N1—C6—C5110.78 (10)C17—C18—H18120.3
C16—C6—C5112.22 (10)O4—C19—C20115.68 (12)
N1—C6—H6107.4O4—C19—C18124.68 (12)
C16—C6—H6107.4C20—C19—C18119.63 (12)
C5—C6—H6107.4C21—C20—C19120.17 (12)
O2—C7—O2'109.5 (3)C21—C20—H20119.9
O2—C7—N1124.4 (3)C19—C20—H20119.9
O2'—C7—N1126.1 (3)C20—C21—C16121.34 (13)
O2—C7—H7117.8C20—C21—H21119.3
N1—C7—H7117.8C16—C21—H21119.3
O2'—C7—H7'116.8O3—C22—H22A109.5
N1—C7—H7'117.2O3—C22—H22B109.5
C13—C8—C9116.86 (13)H22A—C22—H22B109.5
C13—C8—C2120.31 (12)O3—C22—H22C109.5
C9—C8—C2122.79 (12)H22A—C22—H22C109.5
C10—C9—C8121.23 (14)H22B—C22—H22C109.5
C10—C9—H9119.4O4—C23—H23A109.5
C8—C9—H9119.4O4—C23—H23B109.5
C9—C10—C11121.01 (14)H23A—C23—H23B109.5
C9—C10—H10119.5O4—C23—H23C109.5
C11—C10—H10119.5H23A—C23—H23C109.5
O3—C11—C12125.11 (13)H23B—C23—H23C109.5
O3—C11—C10115.89 (13)
C7—N1—C2—C8−109.80 (19)N1—C2—C8—C9−140.48 (13)
C6—N1—C2—C886.30 (14)C3—C2—C8—C9−15.60 (18)
C7—N1—C2—C3121.58 (18)C13—C8—C9—C10−1.5 (2)
C6—N1—C2—C3−42.33 (16)C2—C8—C9—C10−179.28 (14)
N1—C2—C3—C458.59 (14)C8—C9—C10—C110.5 (3)
C8—C2—C3—C4−68.32 (14)C22—O3—C11—C120.1 (2)
N1—C2—C3—C14−63.02 (15)C22—O3—C11—C10178.86 (15)
C8—C2—C3—C14170.07 (11)C9—C10—C11—O3−177.91 (14)
C2—C3—C4—O1160.79 (13)C9—C10—C11—C120.9 (2)
C14—C3—C4—O1−75.37 (17)O3—C11—C12—C13177.39 (14)
C2—C3—C4—C5−20.74 (16)C10—C11—C12—C13−1.3 (2)
C14—C3—C4—C5103.09 (14)C11—C12—C13—C80.3 (2)
O1—C4—C5—C1519.05 (19)C9—C8—C13—C121.1 (2)
C3—C4—C5—C15−159.40 (12)C2—C8—C13—C12178.93 (13)
O1—C4—C5—C6144.05 (13)N1—C6—C16—C1760.77 (17)
C3—C4—C5—C6−34.40 (15)C5—C6—C16—C17−64.16 (17)
C7—N1—C6—C1657.6 (2)N1—C6—C16—C21−120.35 (14)
C2—N1—C6—C16−138.34 (12)C5—C6—C16—C21114.73 (15)
C7—N1—C6—C5−176.69 (17)C21—C16—C17—C181.7 (2)
C2—N1—C6—C5−12.62 (16)C6—C16—C17—C18−179.42 (13)
C4—C5—C6—N151.38 (14)C16—C17—C18—C190.0 (2)
C15—C5—C6—N1176.60 (11)C23—O4—C19—C20173.65 (15)
C4—C5—C6—C16176.69 (10)C23—O4—C19—C18−5.9 (2)
C15—C5—C6—C16−58.09 (15)C17—C18—C19—O4177.91 (13)
C2—N1—C7—O2−150.5 (3)C17—C18—C19—C20−1.7 (2)
C6—N1—C7—O213.6 (4)O4—C19—C20—C21−177.95 (15)
C2—N1—C7—O2'32.2 (4)C18—C19—C20—C211.7 (2)
C6—N1—C7—O2'−163.7 (3)C19—C20—C21—C160.0 (3)
N1—C2—C8—C1341.78 (17)C17—C16—C21—C20−1.7 (2)
C3—C2—C8—C13166.66 (12)C6—C16—C21—C20179.39 (14)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C3—H3···O1i0.982.483.429 (2)163
C15—H15C···O2ii0.962.533.240 (4)131
C20—H20···O1iii0.932.513.432 (2)171

Symmetry codes: (i) −x+2, −y, −z; (ii) x−1/2, −y+1/2, z−1/2; (iii) −x+3/2, y+1/2, −z+1/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: CI2909).

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