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Acta Cryst. (2008). E64, o2312    [ doi:10.1107/S1600536808036325 ]

r-2,c-6-Bis(4-chlorophenyl)-c-3,t-3-dimethylpiperidin-4-one

S. S. Ilango, S. Ponnuswamy, P. Gayathri, A. Thiruvalluvar and R. J. Butcher

Abstract top

In the title molecule, C19H19Cl2NO, the piperidine ring adopts a chair conformation and the dihedral angle between the two benzene rings is 77.23 (7)°. In the crystal structure, molecules are linked by N-H...O and C-H...O hydrogen bonds, and a weak C-H...[pi] interaction is also observed.

Comment top

Piperidones are an important group of heterocyclic compounds in the field of medicinal chemistry due to their biological activities, including cytotoxic and anticancer properties (Dimmock et al., 2001). Piperidones were also reported to possess analgesic, anti-inflammatory, central nervous system (CNS), local anaesthetic, anticancer and antimicrobial activity (Perumal et al., 2001). The design and synthesis of conformationally anchored molecules is an important approach towards improving potency and selectivity. One such class of compounds constitutes piperidin-4-ones and their derivatives, whose synthesis and stereodynamics are well investigated (Ponnuswamy et al., 2002). The crystal structure of r-2,c-6-Bis(4-chlorophenyl)-t-3-isopropyl-1-nitrosopiperidin-4-one has been reported, wherein the piperidine ring adopts a chair conformation (Gayathri et al., 2008).

In the title molecule, C19H19Cl2NO (Fig. 1), the piperidine ring adopts a chair conformation. The phenyl rings at position 2,6 and one of the methyl groups attached to the piperidine ring in 3, have equatorial orientations. The dihedral angle between the two phenyl rings is 77.23 (7)°. In the crystal, the molecules are linked by N1—H1···O4 (x - 1/2, 1/2 - y, z) and C23—H23···O4(x - 1/2, -y + 1/2, z - 1) hydrogen bonds (Table 1). Further, a C31—H31B···π interaction involving the phenyl ring (C61—C66) at position 6 also present in the crystal structure.

Related literature top

For a related crystal structure, see: Gayathri et al. (2008). For background on the biological activities of piperidones, see: Dimmock et al. (2001); Perumal et al. (2001). For the synthesis and stereodynamics of piperidin-4-ones and their derivatives, see: Ponnuswamy et al. (2002). For the synthesis, see: Noller & Baliah (1948). Cg1 is the centroid of the C61–C66 ring.

Experimental top

The procedure adopted for the preparation of the title heterocyclic compound is similar to that of Noller & Baliah (1948). Ammonium acetate (7.7 g, 0.1 mol), 4-chlorobenzaldehyde (28.1 g, 0.2 mol) and 3-methyl-2-butanone (10.7 ml, 0.1 mol) were dissolved in 70 ml of rectified spirit. The resulting solution was heated to boiling and set aside for a day. The oily base obtained was converted into its hydrochloride by the addition of concentrated hydrochloric acid and the separated solid was filtered. Then the hydrochloride was neutralized with liquid ammonia. The resulting solid was filtered and purified by recrystallization from ethanol to yield colourless plates of (I). The yield of the product obtained was 28.65 g (82%).

Refinement top

Atom H1 attached to N1 was located in a difference fourier map and refined isotropically. The remaining H atoms were positioned geometrically and allowed to ride on their parent atoms, with C—H = 0.95, 0.98, 0.99 and 1.00 Å for Csp2, methyl, methylene and methine C, respectively; Uiso(H) = kUeq(C), where k = 1.5 for methyl and 1.2 for all other H atoms.

Computing details top

Data collection: CrysAlis CCD (Oxford Diffraction, 2008); cell refinement: CrysAlis RED (Oxford Diffraction, 2008); data reduction: CrysAlis RED (Oxford Diffraction, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: PLATON (Spek, 2003).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I), showing displacement ellipsoids drawn at the 30% probability level. H atoms are shown as small spheres of arbitrary radius.
[Figure 2] Fig. 2. The packing of (I), viewed down the c axis. Dashed lines indicate hydrogen bonds. H atoms not involved in hydrogen bonding have been omitted.
r-2,c-6-Bis(4-chlorophenyl)-c-3,t-3-dimethylpiperidin-4-one top
Crystal data top
C19H19Cl2NODx = 1.330 Mg m−3
Mr = 348.25Melting point: 402(1) K
Orthorhombic, Pna21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2c -2nCell parameters from 4389 reflections
a = 13.1627 (5) Åθ = 4.5–32.5°
b = 22.4739 (7) ŵ = 0.38 mm−1
c = 5.8794 (2) ÅT = 200 K
V = 1739.23 (10) Å3Rectangular-plate, colourless
Z = 40.44 × 0.31 × 0.22 mm
F(000) = 728
Data collection top
Oxford Diffraction R Gemini
diffractometer		5694 independent reflections
Radiation source: fine-focus sealed tube2460 reflections with I > 2σ(I)
graphiteRint = 0.052
Detector resolution: 10.5081 pixels mm-1θmax = 32.5°, θmin = 4.7°
φ and ω scansh = −18→19
Absorption correction: multi-scan
(CrysAlis RED; Oxford Diffraction, 2008)		k = −33→33
Tmin = 0.950, Tmax = 1.000l = −8→8
19147 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: difmap and geom
R[F2 > 2σ(F2)] = 0.039H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.083 w = 1/[σ2(Fo2) + (0.0371P)2]
where P = (Fo2 + 2Fc2)/3
S = 0.82(Δ/σ)max = 0.001
5694 reflectionsΔρmax = 0.34 e Å−3
212 parametersΔρmin = −0.31 e Å−3
1 restraintAbsolute structure: Flack (1983), 2278 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: −0.03 (5)
Crystal data top
C19H19Cl2NOV = 1739.23 (10) Å3
Mr = 348.25Z = 4
Orthorhombic, Pna21Mo Kα radiation
a = 13.1627 (5) ŵ = 0.38 mm−1
b = 22.4739 (7) ÅT = 200 K
c = 5.8794 (2) Å0.44 × 0.31 × 0.22 mm
Data collection top
Oxford Diffraction R Gemini
diffractometer		5694 independent reflections
Absorption correction: multi-scan
(CrysAlis RED; Oxford Diffraction, 2008)		2460 reflections with I > 2σ(I)
Tmin = 0.950, Tmax = 1.000Rint = 0.052
19147 measured reflectionsθmax = 32.5°
Refinement top
R[F2 > 2σ(F2)] = 0.039H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.083Δρmax = 0.34 e Å−3
S = 0.82Δρmin = −0.31 e Å−3
5694 reflectionsAbsolute structure: Flack (1983), 2278 Friedel pairs
212 parametersFlack parameter: −0.03 (5)
1 restraint
Special details top

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

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 > 2σ(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
Cl10.03898 (4)0.45263 (2)0.55799 (11)0.0585 (2)
Cl20.10182 (5)−0.04812 (2)1.04537 (12)0.0655 (2)
O40.57022 (11)0.24936 (6)1.2121 (2)0.0424 (5)
N10.28387 (13)0.22418 (6)1.0183 (3)0.0312 (5)
C20.32122 (13)0.28540 (7)1.0528 (3)0.0277 (5)
C30.43587 (14)0.28927 (8)0.9833 (3)0.0307 (6)
C40.49124 (15)0.23934 (9)1.1093 (3)0.0341 (6)
C50.44531 (14)0.17905 (9)1.1022 (4)0.0411 (7)
C60.33289 (15)0.18081 (8)1.1659 (3)0.0321 (6)
C210.25298 (15)0.32842 (8)0.9275 (3)0.0312 (6)
C220.21068 (13)0.31249 (8)0.7180 (3)0.0314 (6)
C230.14602 (14)0.35069 (8)0.6055 (3)0.0345 (6)
C240.12245 (15)0.40493 (8)0.7019 (3)0.0352 (6)
C250.16202 (16)0.42206 (8)0.9082 (3)0.0377 (7)
C260.22727 (14)0.38327 (8)1.0207 (3)0.0347 (6)
C310.47926 (14)0.34992 (8)1.0480 (4)0.0439 (7)
C320.45062 (15)0.27850 (10)0.7274 (3)0.0426 (7)
C610.27905 (14)0.12205 (8)1.1398 (3)0.0305 (6)
C620.28440 (17)0.08976 (9)0.9400 (3)0.0439 (7)
C630.23098 (19)0.03820 (9)0.9104 (4)0.0504 (8)
C640.17155 (15)0.01751 (8)1.0837 (4)0.0424 (7)
C650.16451 (18)0.04755 (10)1.2868 (4)0.0461 (8)
C660.21822 (16)0.09989 (10)1.3129 (3)0.0432 (8)
H10.2194 (13)0.2237 (7)1.032 (3)0.023 (5)*
H20.316310.294601.218870.0333*
H5A0.481910.152621.209100.0493*
H5B0.452760.162360.947240.0493*
H60.326390.194361.327220.0385*
H220.226670.274980.652620.0376*
H230.117900.339760.462700.0414*
H250.145170.459570.972510.0452*
H260.254770.394441.163840.0416*
H31A0.442410.381200.966230.0659*
H31B0.551390.351481.007000.0659*
H31C0.471870.356031.212170.0659*
H32A0.415640.309730.641330.0639*
H32B0.422350.239620.686370.0639*
H32C0.523280.279300.691130.0639*
H620.326360.103800.819980.0527*
H630.235130.016990.770960.0605*
H650.123500.032591.406820.0553*
H660.213430.121141.452150.0519*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0547 (3)0.0505 (3)0.0703 (4)0.0179 (3)−0.0132 (4)0.0120 (3)
Cl20.0681 (4)0.0421 (3)0.0864 (4)−0.0195 (3)−0.0183 (4)0.0074 (3)
O40.0273 (8)0.0530 (9)0.0468 (8)−0.0024 (7)−0.0046 (8)0.0054 (7)
N10.0184 (9)0.0324 (8)0.0427 (10)0.0015 (7)−0.0010 (8)0.0036 (7)
C20.0273 (10)0.0267 (9)0.0292 (9)0.0009 (8)0.0047 (10)0.0017 (10)
C30.0262 (11)0.0338 (10)0.0321 (10)−0.0012 (9)0.0015 (9)0.0010 (8)
C40.0225 (10)0.0414 (12)0.0385 (11)0.0026 (9)0.0030 (10)−0.0003 (9)
C50.0293 (11)0.0359 (11)0.0581 (14)0.0052 (9)−0.0109 (11)0.0094 (11)
C60.0329 (11)0.0306 (10)0.0328 (9)0.0049 (9)−0.0053 (9)0.0087 (8)
C210.0223 (10)0.0374 (12)0.0339 (10)−0.0015 (9)0.0035 (9)−0.0045 (9)
C220.0337 (11)0.0273 (10)0.0331 (10)−0.0018 (9)−0.0029 (10)−0.0017 (8)
C230.0307 (11)0.0362 (10)0.0366 (11)0.0023 (9)−0.0043 (9)0.0008 (9)
C240.0306 (11)0.0327 (11)0.0424 (11)0.0012 (9)−0.0018 (10)0.0117 (10)
C250.0354 (12)0.0304 (11)0.0472 (11)0.0037 (10)0.0028 (11)−0.0011 (10)
C260.0282 (10)0.0364 (10)0.0394 (10)0.0017 (9)−0.0005 (10)−0.0045 (9)
C310.0355 (11)0.0386 (11)0.0577 (12)−0.0024 (9)−0.0058 (13)−0.0094 (11)
C320.0360 (13)0.0550 (14)0.0368 (11)−0.0003 (10)0.0049 (11)0.0074 (11)
C610.0304 (11)0.0246 (9)0.0364 (10)0.0045 (9)−0.0026 (9)0.0077 (8)
C620.0537 (15)0.0387 (12)0.0393 (11)−0.0057 (11)0.0080 (11)0.0021 (10)
C630.0657 (17)0.0362 (13)0.0493 (12)−0.0036 (12)−0.0009 (14)−0.0095 (11)
C640.0390 (12)0.0308 (10)0.0573 (14)−0.0048 (9)−0.0099 (13)0.0126 (12)
C650.0384 (14)0.0485 (14)0.0514 (13)−0.0074 (11)−0.0026 (11)0.0076 (11)
C660.0445 (14)0.0455 (14)0.0397 (11)−0.0003 (12)−0.0064 (11)0.0015 (10)
Geometric parameters (Å, °) top
Cl1—C241.7528 (19)C62—C631.367 (3)
Cl2—C641.7518 (19)C63—C641.366 (3)
O4—C41.223 (2)C64—C651.375 (3)
N1—C21.475 (2)C65—C661.381 (3)
N1—C61.456 (2)C2—H21.0000
N1—H10.853 (17)C5—H5A0.9900
C2—C31.566 (3)C5—H5B0.9900
C2—C211.511 (2)C6—H61.0000
C3—C311.526 (3)C22—H220.9500
C3—C321.536 (3)C23—H230.9500
C3—C41.529 (3)C25—H250.9500
C4—C51.484 (3)C26—H260.9500
C5—C61.527 (3)C31—H31A0.9800
C6—C611.507 (3)C31—H31B0.9800
C21—C221.398 (3)C31—H31C0.9800
C21—C261.391 (3)C32—H32A0.9800
C22—C231.378 (3)C32—H32B0.9800
C23—C241.380 (3)C32—H32C0.9800
C24—C251.375 (3)C62—H620.9500
C25—C261.391 (3)C63—H630.9500
C61—C661.387 (3)C65—H650.9500
C61—C621.383 (3)C66—H660.9500
C2—N1—C6113.25 (15)N1—C2—H2108.00
C6—N1—H1112.1 (11)C3—C2—H2108.00
C2—N1—H1109.3 (11)C21—C2—H2108.00
N1—C2—C21109.36 (14)C4—C5—H5A109.00
N1—C2—C3109.70 (14)C4—C5—H5B109.00
C3—C2—C21114.21 (14)C6—C5—H5A109.00
C2—C3—C31110.20 (14)C6—C5—H5B109.00
C2—C3—C4106.98 (14)H5A—C5—H5B108.00
C4—C3—C32107.37 (15)N1—C6—H6109.00
C31—C3—C32109.73 (16)C5—C6—H6109.00
C4—C3—C31110.87 (15)C61—C6—H6109.00
C2—C3—C32111.63 (15)C21—C22—H22120.00
O4—C4—C5121.87 (18)C23—C22—H22120.00
O4—C4—C3120.61 (17)C22—C23—H23120.00
C3—C4—C5117.52 (16)C24—C23—H23120.00
C4—C5—C6111.36 (16)C24—C25—H25121.00
N1—C6—C5107.50 (15)C26—C25—H25121.00
C5—C6—C61114.09 (16)C21—C26—H26119.00
N1—C6—C61108.52 (15)C25—C26—H26119.00
C2—C21—C26121.30 (16)C3—C31—H31A109.00
C2—C21—C22120.15 (16)C3—C31—H31B109.00
C22—C21—C26118.50 (17)C3—C31—H31C109.00
C21—C22—C23120.61 (17)H31A—C31—H31B109.00
C22—C23—C24119.48 (17)H31A—C31—H31C109.00
C23—C24—C25121.64 (17)H31B—C31—H31C109.00
Cl1—C24—C25119.47 (14)C3—C32—H32A109.00
Cl1—C24—C23118.88 (14)C3—C32—H32B109.00
C24—C25—C26118.54 (17)C3—C32—H32C109.00
C21—C26—C25121.22 (17)H32A—C32—H32B109.00
C62—C61—C66117.66 (18)H32A—C32—H32C109.00
C6—C61—C62121.51 (17)H32B—C32—H32C109.00
C6—C61—C66120.76 (16)C61—C62—H62119.00
C61—C62—C63121.81 (19)C63—C62—H62119.00
C62—C63—C64119.2 (2)C62—C63—H63120.00
Cl2—C64—C65119.33 (17)C64—C63—H63120.00
Cl2—C64—C63119.38 (17)C64—C65—H65121.00
C63—C64—C65121.28 (19)C66—C65—H65121.00
C64—C65—C66118.7 (2)C61—C66—H66119.00
C61—C66—C65121.31 (18)C65—C66—H66119.00
C6—N1—C2—C364.86 (19)N1—C6—C61—C6268.3 (2)
C6—N1—C2—C21−169.16 (15)N1—C6—C61—C66−108.6 (2)
C2—N1—C6—C5−64.02 (19)C5—C6—C61—C62−51.5 (2)
C2—N1—C6—C61172.13 (15)C5—C6—C61—C66131.6 (2)
N1—C2—C3—C4−51.75 (18)C2—C21—C22—C23178.11 (17)
N1—C2—C3—C31−172.37 (15)C26—C21—C22—C230.8 (3)
N1—C2—C3—C3265.44 (19)C2—C21—C26—C25−178.05 (17)
C21—C2—C3—C4−174.92 (14)C22—C21—C26—C25−0.8 (3)
C21—C2—C3—C3164.5 (2)C21—C22—C23—C24−0.5 (3)
C21—C2—C3—C32−57.7 (2)C22—C23—C24—Cl1−179.30 (14)
N1—C2—C21—C22−36.1 (2)C22—C23—C24—C250.1 (3)
N1—C2—C21—C26141.12 (18)Cl1—C24—C25—C26179.33 (15)
C3—C2—C21—C2287.3 (2)C23—C24—C25—C26−0.1 (3)
C3—C2—C21—C26−95.5 (2)C24—C25—C26—C210.4 (3)
C2—C3—C4—O4−132.07 (17)C6—C61—C62—C63−176.1 (2)
C2—C3—C4—C547.7 (2)C66—C61—C62—C630.9 (3)
C31—C3—C4—O4−11.9 (2)C6—C61—C66—C65176.77 (19)
C31—C3—C4—C5167.88 (17)C62—C61—C66—C65−0.2 (3)
C32—C3—C4—O4107.97 (19)C61—C62—C63—C64−0.8 (3)
C32—C3—C4—C5−72.3 (2)C62—C63—C64—Cl2179.29 (17)
O4—C4—C5—C6129.70 (19)C62—C63—C64—C650.0 (3)
C3—C4—C5—C6−50.1 (2)Cl2—C64—C65—C66−178.65 (17)
C4—C5—C6—N153.9 (2)C63—C64—C65—C660.6 (3)
C4—C5—C6—C61174.28 (16)C64—C65—C66—C61−0.5 (3)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O4i0.853 (17)2.312 (17)3.092 (2)152.3 (15)
C23—H23···O4ii0.952.563.377 (2)144
C31—H31B···Cg1iii0.982.963.7265 (15)136
Symmetry codes: (i) x−1/2, −y+1/2, z; (ii) x−1/2, −y+1/2, z−1; (iii) x+1/2, −y+1/2, z.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O4i0.853 (17)2.312 (17)3.092 (2)152.3 (15)
C23—H23···O4ii0.952.563.377 (2)144
C31—H31B···Cg1iii0.982.963.7265 (15)136
Symmetry codes: (i) x−1/2, −y+1/2, z; (ii) x−1/2, −y+1/2, z−1; (iii) x+1/2, −y+1/2, z.
Acknowledgements top

AT thanks the UGC, India, for the award of a Minor Research Project [File No. MRP-2355/06(UGC-SERO), Link No. 2355, 10/01/2007]. RJB acknowledges the NSF–MRI program for funding the purchase of the X-ray CCD diffractometer.

references
References top

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