1-Chloro-acetyl-2,6-bis-(3-fluoro-phen-yl)piperidin-4-one.

In the title compound C(19)H(16)ClF(2)NO(2), the piperidone ring adopts a twist-boat conformation with the two out-of-plane atoms deviating by 0.544 (1) and 0.511 (1) Å from the plane through the remaining atoms in the ring. Sterically favoured non-H-atom C⋯O inter-molecular contacts are observed in the structure, within a 3.00 Å range. The crystal packing is stabilized by C-H⋯O and C-H⋯F hydrogen bonds and an inter-molecular π-π inter-action [centroid-centroid separation of 3.783 (1) Å]. Alternating C-H⋯O and C-H⋯F inter-molecular inter-actions generate chains running along the a axis, while a centrosymmetric R(2) (2)(16) ring involving C-H⋯O inter-actions is formed centred at (1/2, 1/2, 0).

Related literature

For background to the biological activity of piperidines and piperidones and their derivatives, see: Richardo et al. (1979 ▶); Schneider (1996 ▶); Mukhtar & Wright (2005 ▶); Fleet et al. (1990 ▶); Winkler & Holan (1989 ▶); Aridoss et al. (2007a ▶, 2008 ▶, 2009a ▶). For related structures, see: Gayathri et al. (2008 ▶); Ramachandran et al. (2008 ▶); Aridoss et al. (2009b ▶). For the synthesis and stereochemistry, see: Krishnapillay et al. (2000 ▶); Aridoss et al. (2007b ▶). For ring conformational analysis, see: Cremer & Pople (1975 ▶); Nardelli (1983 ▶).

Experimental

Crystal data

C19H16ClF2NO2

M = 363.78

Monoclinic,

a = 10.7026 (8) Å

b = 8.2017 (6) Å

c = 19.0447 (15) Å

β = 100.629 (1)°

V = 1643.1 (2) Å3

Z = 4

Mo Kα radiation

μ = 0.27 mm−1

T = 293 K

0.29 × 0.25 × 0.22 mm

Data collection

Bruker SMART APEX diffractometer

Absorption correction: none

18143 measured reflections

3875 independent reflections

3515 reflections with I > 2σ(I)

R int = 0.018

Refinement

R[F 2 > 2σ(F 2)] = 0.039

wR(F 2) = 0.111

S = 1.03

3875 reflections

226 parameters

H-atom parameters constrained

Δρmax = 0.34 e Å−3

Δρmin = −0.35 e Å−3

Data collection: SMART (Bruker, 2001 ▶); cell refinement: SAINT (Bruker, 2001 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: SHELXL97 and PARST (Nardelli, 1995 ▶).

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809028529/bg2281sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809028529/bg2281Isup2.hkl

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

C19H16ClF2NO2	F(000) = 752
Mr = 363.78	Dx = 1.471 Mg m−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 2558 reflections
a = 10.7026 (8) Å	θ = 2.0–28.1°
b = 8.2017 (6) Å	µ = 0.27 mm−1
c = 19.0447 (15) Å	T = 293 K
β = 100.629 (1)°	Block, colorless
V = 1643.1 (2) Å3	0.29 × 0.25 × 0.22 mm
Z = 4

Bruker SMART APEX diffractometer	3515 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.018
graphite	θmax = 28.1°, θmin = 2.0°
ω scans	h = −14→13
18143 measured reflections	k = −10→10
3875 independent reflections	l = −25→24

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.039	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.111	H-atom parameters constrained
S = 1.03	w = 1/[σ2(Fo2) + (0.0604P)2 + 0.4707P] where P = (Fo2 + 2Fc2)/3
3875 reflections	(Δ/σ)max < 0.001
226 parameters	Δρmax = 0.34 e Å−3
0 restraints	Δρmin = −0.35 e Å−3

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.

	x	y	z	Uiso*/Ueq
C1	0.19220 (11)	0.60188 (15)	0.12209 (7)	0.0342 (3)
H1	0.1633	0.4907	0.1291	0.041*
C2	0.14537 (12)	0.70807 (17)	0.17787 (7)	0.0391 (3)
H2A	0.0532	0.7101	0.1680	0.047*
H2B	0.1725	0.6601	0.2248	0.047*
C3	0.19437 (12)	0.87902 (16)	0.17849 (6)	0.0355 (3)
C4	0.31441 (12)	0.89729 (15)	0.14859 (7)	0.0366 (3)
H4A	0.3605	0.9917	0.1705	0.044*
H4B	0.2914	0.9184	0.0977	0.044*
C5	0.40356 (11)	0.74875 (14)	0.15997 (6)	0.0315 (2)
H5	0.4393	0.7400	0.2111	0.038*
C6	0.38663 (12)	0.44552 (15)	0.14846 (6)	0.0342 (3)
C7	0.52903 (13)	0.44165 (16)	0.17627 (8)	0.0437 (3)
H7A	0.5478	0.4980	0.2218	0.052*
H7B	0.5722	0.4986	0.1430	0.052*
C8	0.14016 (11)	0.64593 (15)	0.04440 (7)	0.0359 (3)
C9	0.18650 (13)	0.56233 (18)	−0.00921 (8)	0.0438 (3)
H9	0.2497	0.4839	0.0024	0.053*
C10	0.13769 (15)	0.5973 (2)	−0.07922 (8)	0.0497 (3)
C11	0.04478 (16)	0.7120 (2)	−0.09979 (8)	0.0530 (4)
H11	0.0147	0.7346	−0.1478	0.064*
C12	−0.00203 (16)	0.7923 (2)	−0.04692 (9)	0.0548 (4)
H12	−0.0659	0.8695	−0.0593	0.066*
C13	0.04442 (14)	0.76014 (18)	0.02456 (8)	0.0459 (3)
H13	0.0112	0.8156	0.0596	0.055*
C14	0.51171 (11)	0.78384 (15)	0.12008 (7)	0.0330 (2)
C15	0.62680 (12)	0.84067 (18)	0.15766 (8)	0.0420 (3)
H15	0.6415	0.8480	0.2072	0.050*
C16	0.71890 (13)	0.8861 (2)	0.11948 (9)	0.0528 (4)
C17	0.70255 (15)	0.8775 (2)	0.04699 (10)	0.0558 (4)
H17	0.7667	0.9098	0.0231	0.067*
C18	0.58841 (15)	0.8196 (2)	0.01009 (8)	0.0507 (4)
H18	0.5751	0.8119	−0.0394	0.061*
C19	0.49307 (14)	0.77279 (17)	0.04628 (7)	0.0416 (3)
H19	0.4163	0.7338	0.0209	0.050*
N1	0.33311 (9)	0.59708 (12)	0.13708 (5)	0.0316 (2)
O1	0.14246 (10)	0.99449 (13)	0.20033 (6)	0.0477 (2)
O2	0.32477 (10)	0.32101 (12)	0.13649 (6)	0.0467 (2)
F1	0.18216 (12)	0.51239 (17)	−0.13076 (6)	0.0785 (3)
F2	0.83117 (10)	0.9428 (2)	0.15588 (7)	0.0907 (4)
Cl1	0.58658 (4)	0.24037 (5)	0.18722 (3)	0.06261 (15)

	U11	U22	U33	U12	U13	U23
C1	0.0292 (5)	0.0319 (6)	0.0411 (6)	−0.0020 (4)	0.0055 (5)	0.0025 (5)
C2	0.0355 (6)	0.0431 (7)	0.0411 (6)	0.0005 (5)	0.0129 (5)	0.0045 (5)
C3	0.0356 (6)	0.0407 (7)	0.0299 (5)	0.0040 (5)	0.0056 (4)	−0.0001 (5)
C4	0.0389 (6)	0.0302 (6)	0.0422 (6)	−0.0006 (5)	0.0118 (5)	−0.0019 (5)
C5	0.0318 (6)	0.0319 (6)	0.0309 (5)	−0.0024 (4)	0.0060 (4)	−0.0012 (4)
C6	0.0375 (6)	0.0327 (6)	0.0328 (5)	0.0023 (5)	0.0075 (5)	0.0006 (4)
C7	0.0392 (7)	0.0337 (6)	0.0572 (8)	0.0069 (5)	0.0060 (6)	0.0044 (6)
C8	0.0310 (6)	0.0328 (6)	0.0420 (6)	−0.0048 (5)	0.0020 (5)	−0.0005 (5)
C9	0.0399 (7)	0.0435 (7)	0.0458 (7)	0.0008 (5)	0.0021 (5)	−0.0040 (6)
C10	0.0496 (8)	0.0558 (9)	0.0434 (7)	−0.0096 (7)	0.0075 (6)	−0.0066 (6)
C11	0.0545 (8)	0.0570 (9)	0.0425 (7)	−0.0111 (7)	−0.0043 (6)	0.0087 (7)
C12	0.0507 (8)	0.0511 (8)	0.0571 (9)	0.0078 (7)	−0.0045 (7)	0.0090 (7)
C13	0.0414 (7)	0.0447 (8)	0.0495 (8)	0.0051 (6)	0.0026 (6)	0.0006 (6)
C14	0.0319 (6)	0.0297 (5)	0.0383 (6)	0.0006 (4)	0.0091 (5)	0.0008 (4)
C15	0.0356 (6)	0.0450 (7)	0.0443 (7)	−0.0028 (5)	0.0046 (5)	0.0046 (6)
C16	0.0303 (6)	0.0584 (9)	0.0685 (10)	−0.0043 (6)	0.0056 (6)	0.0149 (7)
C17	0.0423 (8)	0.0624 (10)	0.0686 (10)	0.0073 (7)	0.0261 (7)	0.0195 (8)
C18	0.0588 (9)	0.0532 (9)	0.0451 (7)	0.0056 (7)	0.0227 (7)	0.0028 (6)
C19	0.0437 (7)	0.0433 (7)	0.0388 (6)	−0.0024 (5)	0.0104 (5)	−0.0027 (5)
N1	0.0294 (5)	0.0295 (5)	0.0353 (5)	−0.0005 (4)	0.0041 (4)	0.0020 (4)
O1	0.0472 (5)	0.0474 (6)	0.0510 (6)	0.0082 (4)	0.0157 (4)	−0.0071 (4)
O2	0.0474 (5)	0.0311 (5)	0.0601 (6)	−0.0014 (4)	0.0060 (4)	−0.0032 (4)
F1	0.0865 (8)	0.0996 (9)	0.0501 (6)	0.0098 (7)	0.0145 (5)	−0.0162 (6)
F2	0.0411 (5)	0.1322 (12)	0.0927 (8)	−0.0331 (6)	−0.0035 (5)	0.0304 (8)
Cl1	0.0550 (2)	0.0405 (2)	0.0879 (3)	0.01621 (16)	0.0017 (2)	0.00367 (18)

C1—N1	1.4827 (15)	C8—C9	1.3948 (19)
C1—C8	1.5251 (17)	C9—C10	1.370 (2)
C1—C2	1.5279 (18)	C9—H9	0.9300
C1—H1	0.9800	C10—F1	1.3590 (19)
C2—C3	1.4963 (19)	C10—C11	1.373 (2)
C2—H2A	0.9700	C11—C12	1.373 (3)
C2—H2B	0.9700	C11—H11	0.9300
C3—O1	1.2099 (16)	C12—C13	1.386 (2)
C3—C4	1.5056 (17)	C12—H12	0.9300
C4—C5	1.5379 (17)	C13—H13	0.9300
C4—H4A	0.9700	C14—C19	1.3857 (18)
C4—H4B	0.9700	C14—C15	1.3861 (18)
C5—N1	1.4781 (15)	C15—C16	1.380 (2)
C5—C14	1.5246 (16)	C15—H15	0.9300
C5—H5	0.9800	C16—F2	1.3542 (18)
C6—O2	1.2154 (16)	C16—C17	1.361 (2)
C6—N1	1.3691 (15)	C17—C18	1.376 (2)
C6—C7	1.5187 (18)	C17—H17	0.9300
C7—Cl1	1.7609 (14)	C18—C19	1.387 (2)
C7—H7A	0.9700	C18—H18	0.9300
C7—H7B	0.9700	C19—H19	0.9300
C8—C13	1.3883 (19)
N1—C1—C8	111.69 (10)	C9—C8—C1	118.56 (12)
N1—C1—C2	109.49 (10)	C10—C9—C8	119.11 (14)
C8—C1—C2	115.56 (11)	C10—C9—H9	120.4
N1—C1—H1	106.5	C8—C9—H9	120.4
C8—C1—H1	106.5	F1—C10—C9	118.32 (15)
C2—C1—H1	106.5	F1—C10—C11	118.48 (14)
C3—C2—C1	112.34 (10)	C9—C10—C11	123.19 (15)
C3—C2—H2A	109.1	C12—C11—C10	117.56 (14)
C1—C2—H2A	109.1	C12—C11—H11	121.2
C3—C2—H2B	109.1	C10—C11—H11	121.2
C1—C2—H2B	109.1	C11—C12—C13	121.06 (15)
H2A—C2—H2B	107.9	C11—C12—H12	119.5
O1—C3—C2	123.62 (12)	C13—C12—H12	119.5
O1—C3—C4	122.01 (12)	C12—C13—C8	120.59 (15)
C2—C3—C4	114.36 (10)	C12—C13—H13	119.7
C3—C4—C5	114.73 (10)	C8—C13—H13	119.7
C3—C4—H4A	108.6	C19—C14—C15	119.59 (12)
C5—C4—H4A	108.6	C19—C14—C5	120.83 (11)
C3—C4—H4B	108.6	C15—C14—C5	119.36 (11)
C5—C4—H4B	108.6	C16—C15—C14	118.16 (13)
H4A—C4—H4B	107.6	C16—C15—H15	120.9
N1—C5—C14	113.88 (9)	C14—C15—H15	120.9
N1—C5—C4	110.83 (10)	F2—C16—C17	118.22 (14)
C14—C5—C4	106.77 (9)	F2—C16—C15	118.41 (15)
N1—C5—H5	108.4	C17—C16—C15	123.37 (14)
C14—C5—H5	108.4	C16—C17—C18	118.13 (13)
C4—C5—H5	108.4	C16—C17—H17	120.9
O2—C6—N1	122.39 (11)	C18—C17—H17	120.9
O2—C6—C7	121.65 (11)	C17—C18—C19	120.47 (14)
N1—C6—C7	115.96 (11)	C17—C18—H18	119.8
C6—C7—Cl1	111.56 (10)	C19—C18—H18	119.8
C6—C7—H7A	109.3	C14—C19—C18	120.29 (14)
Cl1—C7—H7A	109.3	C14—C19—H19	119.9
C6—C7—H7B	109.3	C18—C19—H19	119.9
Cl1—C7—H7B	109.3	C6—N1—C5	122.80 (10)
H7A—C7—H7B	108.0	C6—N1—C1	115.82 (10)
C13—C8—C9	118.47 (13)	C5—N1—C1	118.67 (9)
C13—C8—C1	122.89 (12)
N1—C1—C2—C3	59.23 (13)	C4—C5—C14—C19	−75.31 (14)
C8—C1—C2—C3	−67.92 (14)	N1—C5—C14—C15	−138.10 (12)
C1—C2—C3—O1	156.26 (12)	C4—C5—C14—C15	99.24 (13)
C1—C2—C3—C4	−23.06 (15)	C19—C14—C15—C16	0.6 (2)
O1—C3—C4—C5	149.28 (12)	C5—C14—C15—C16	−173.98 (13)
C2—C3—C4—C5	−31.38 (15)	C14—C15—C16—F2	179.52 (14)
C3—C4—C5—N1	50.02 (14)	C14—C15—C16—C17	−0.2 (2)
C3—C4—C5—C14	174.56 (10)	F2—C16—C17—C18	179.94 (16)
O2—C6—C7—Cl1	0.30 (17)	C15—C16—C17—C18	−0.4 (3)
N1—C6—C7—Cl1	−179.00 (9)	C16—C17—C18—C19	0.4 (2)
N1—C1—C8—C13	−134.11 (13)	C15—C14—C19—C18	−0.6 (2)
C2—C1—C8—C13	−8.06 (18)	C5—C14—C19—C18	173.95 (13)
N1—C1—C8—C9	49.02 (15)	C17—C18—C19—C14	0.0 (2)
C2—C1—C8—C9	175.06 (11)	O2—C6—N1—C5	171.94 (12)
C13—C8—C9—C10	1.0 (2)	C7—C6—N1—C5	−8.77 (16)
C1—C8—C9—C10	178.01 (12)	O2—C6—N1—C1	10.87 (17)
C8—C9—C10—F1	−178.72 (13)	C7—C6—N1—C1	−169.84 (11)
C8—C9—C10—C11	0.3 (2)	C14—C5—N1—C6	66.79 (14)
F1—C10—C11—C12	177.74 (15)	C4—C5—N1—C6	−172.80 (10)
C9—C10—C11—C12	−1.2 (2)	C14—C5—N1—C1	−132.65 (11)
C10—C11—C12—C13	1.0 (3)	C4—C5—N1—C1	−12.24 (14)
C11—C12—C13—C8	0.3 (3)	C8—C1—N1—C6	−109.19 (12)
C9—C8—C13—C12	−1.3 (2)	C2—C1—N1—C6	121.50 (11)
C1—C8—C13—C12	−178.13 (13)	C8—C1—N1—C5	88.92 (13)
N1—C5—C14—C19	47.35 (16)	C2—C1—N1—C5	−40.39 (14)

D—H···A	D—H	H···A	D···A	D—H···A
C2—H2B···O1i	0.97	2.60	3.415 (2)	142
C7—H7A···F2ii	0.97	2.49	3.270 (2)	137
C18—H18···O2iii	0.93	2.55	3.308 (2)	139

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C2—H2B⋯O1i	0.97	2.60	3.415 (2)	142
C7—H7A⋯F2ii	0.97	2.49	3.270 (2)	137
C18—H18⋯O2iii	0.93	2.55	3.308 (2)	139

Symmetry codes: (i) ; (ii) ; (iii) .