Crystal structure of (4-hy­droxy­piperidin-1-yl)(4-methyl­phen­yl)methanone

Abstract

In the title compound, C₁₃H₁₇NO₂, the dihedral angle between the planes of the piperidine and benzene rings is 51.7 (2)°. The bond-angle sum around the N atom [359.8 (3)°] indicates sp ² hybridization of the atom. In the crystal, O—H⋯O hydrogen bonds link the mol­ecules, forming chains along [001].

Related literature  

For the biological activity of piperdine derivatives, see: Pissamitski et al. (2007 ▸); Katritzky et al. (1995 ▸); Dimmock et al. (2001 ▸); Watson et al. (2000 ▸); Thomas et al. (1998 ▸); Sambath et al. (2004 ▸). For related structures, see: Revathi et al. (2015 ▸); Prathebha et al. (2015 ▸). For the synthesis, see: Revathi et al. (2015 ▸).

Experimental  

Crystal data  

• C₁₃H₁₇NO₂

• M _r = 219.28

• Orthorhombic,

• a = 23.933 (5) Å

• b = 6.3317 (12) Å

• c = 8.0269 (14) Å

• V = 1216.3 (4) ų

• Z = 4

• Mo Kα radiation

• μ = 0.08 mm⁻¹

• T = 293 K

• 0.24 × 0.22 × 0.22 mm

Data collection  

• Bruker Kappa APEXII CCD diffractometer

• Absorption correction: multi-scan (SADABS; Bruker, 2004 ▸) T _min = 0.981, T _max = 0.985

• 10595 measured reflections

• 3454 independent reflections

• 1668 reflections with I > 2σ(I)

• R _int = 0.039

Refinement  

• R[F ² > 2σ(F ²)] = 0.066

• wR(F ²) = 0.208

• S = 1.04

• 3454 reflections

• 145 parameters

• 1 restraint

• H-atom parameters constrained

• Δρ_max = 0.28 e Å⁻³

• Δρ_min = −0.22 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▸); cell refinement: APEX2 and SAINT (Bruker, 2004 ▸); data reduction: SAINT and XPREP (Bruker, 2004 ▸); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▸); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▸); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▸); software used to prepare material for publication: SHELXL97.

Supplementary Material

CCDC reference: 1428660

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (, ).

DHA	DH	HA	D A	DHA
O2H2AO1i	0.82	1.97	2.741(4)	156

Symmetry code: (i) .

supplementary crystallographic information

S1. Comment

The piperidine ring is one of the most recognizable structural entities among heterocyclic molecules (Katritzky, 1995). A piperidine series of gamma-secretase inhibitors have been evaluated for treatment of Alzheimer's disease (AD) (Pissamitski et al., 2007). Some piperidines were found to possess high profile biological activities, including cytotoxic and anticancer properties (Dimmock et al., 2001). The piperidine ring is a feature of oral anaesthetics and narcotic analgesics (Watson et al., 2000); Thomas et al., 1998). Piperidine derivatives are used clinically to prevent post-operative vomiting, to speed up gastric emptying before anaesthesia, to facilitate radiological investigations and to correct a variety of disturbances of gastrointestinal functions (Sambath et al., 2004).

The title compound, C₁₃H₁₇NO₂, has been synthesized and the structure (Fig. 1) is reported herein. In this compound, The C—C distances in the piperidine ring and the benzene ring are in the range 1.497 (6)–1.515 (5) Å and 1.357 (6)–1.386 (5) Å, respectively and are comparable with literature values. The C—N distances in the piperidine ring are 1.455 (5) Å and 1.462 (5) Å] and are in good agreement with values in a similar reported structure (Revathi et al., 2015). The C7—O1 distance is 1.238 (5) Å, indicating double bond character and is comparable with the value reported previously (Prathebha et al., 2015). The dihedral angle between piperidine and benzene rings is 51.7 (2)°. The bond angle sum around the N1 atom are 359.8 (3)° indicating an sp² hybridization of the atoms. The C8—N1—C7—O1 torsion angle [-9.0 (6)°] indicates that the keto group is in a syn-periplanar (-sp) orientation with respect to the piperidine ring which adopts a chair conformation, with puckering parameters of q2 = 0.016 (4) Å, φ2 = 168.41° q3 = -0.560 (4) Å, QT = 0.561 (4) Å and θ2 = 178.38 (4)°.

The crystal packing is stabilized by a single intermolecular O2—H···O1ⁱ hydrogen bond (Table 1), forming one-dimensional chains which extend along [001] (Fig. 2). Present also in the structure is a short intramolecular C8—H···O1 interaction [2.740 (5) Å].

S2. Experimental

The title compound was synthesized using a published procedure (Revathi et al., 2015). In a 250 ml round-bottomed flask, 120 mL of ethyl methyl ketone was added to 4-hydroxypiperdine (0.02 mol) and stirred at room temperature. After 5 min, triethylamine (0.04 mol) was added and the mixture was stirred for 15 min. 4-Methyl benzoyl chloride (0.04 mol) was then added and the reaction mixture was stirred at room temperature for ca. 2 h. A white precipitate of triethylammonium chloride was formed, which was removed by filtration and the filtrate was evaporated to give the crude product. This was recrystallized twice from ethyl methyl ketone giving colourless block-like crystals of the title compound (yield: 82%).

S3. Refinement

H atoms were positioned geometrically and treated as riding on their parent atoms and refined with C—H distances of 0.93–0.98 Å and an O—H distance of 0.82 Å, with U_iso(H) = 1.5 U_eq(C-methyl and O), U_iso(H)= 1.2Ueq(C, O) for other H atoms. One reflection (2 0 0) was considered to be affected by the beamstop and was omitted. The value of the absolute structure factor (Flack, 1983), although not of particular relevance but meaningless in this structure, was determined as 0(3) for 1610 Friedel pairs.

Figures

Fig. 1.

The molecular structure and atom numbering scheme for the title compound, with displacement ellipsoids drawn at the 30% probability level.

Fig. 2.

The crystal packing in the unit cell viewed along b. The dashed lines indicate hydrogen bonds.

Crystal data

C13H17NO2	F(000) = 472
Mr = 219.28	Dx = 1.197 Mg m−3
Orthorhombic, Pca21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2c -2ac	θ = 1.7–29.8°
a = 23.933 (5) Å	µ = 0.08 mm−1
b = 6.3317 (12) Å	T = 293 K
c = 8.0269 (14) Å	Block, colourless
V = 1216.3 (4) Å3	0.24 × 0.22 × 0.22 mm
Z = 4

Data collection

Bruker Kappa APEXII CCD diffractometer	3454 independent reflections
Radiation source: fine-focus sealed tube	1668 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.039
ω and φ scans	θmax = 29.8°, θmin = 3.1°
Absorption correction: multi-scan (SADABS; Bruker, 2004)	h = −33→30
Tmin = 0.981, Tmax = 0.985	k = −8→8
10595 measured reflections	l = −10→11

Refinement

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)] = 0.066	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.208	H-atom parameters constrained
S = 1.04	w = 1/[σ2(Fo2) + (0.121P)2 + 0.297P] where P = (Fo2 + 2Fc2)/3
3454 reflections	(Δ/σ)max < 0.001
145 parameters	Δρmax = 0.28 e Å−3
1 restraint	Δρmin = −0.22 e Å−3

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 > 2sigma(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 (Ų)

	x	y	z	Uiso*/Ueq
O2	0.42250 (13)	0.9019 (5)	0.2011 (4)	0.0766 (9)
H2A	0.4137	0.8390	0.1158	0.115*
N1	0.43269 (12)	0.5768 (5)	0.6446 (4)	0.0502 (8)
O1	0.42609 (13)	0.6719 (6)	0.9120 (3)	0.0885 (11)
C10	0.44267 (16)	0.7574 (6)	0.3187 (5)	0.0533 (9)
H10	0.4759	0.6870	0.2737	0.064*
C4	0.35949 (13)	0.4254 (6)	0.8163 (4)	0.0482 (8)
C1	0.26666 (15)	0.1641 (8)	0.8753 (5)	0.0628 (11)
C12	0.41754 (16)	0.4528 (6)	0.4989 (5)	0.0545 (9)
H12A	0.3877	0.3558	0.5279	0.065*
H12B	0.4495	0.3701	0.4632	0.065*
C7	0.40802 (15)	0.5691 (6)	0.7925 (4)	0.0505 (9)
C11	0.39864 (16)	0.5930 (6)	0.3578 (4)	0.0524 (9)
H11A	0.3640	0.6627	0.3883	0.063*
H11B	0.3916	0.5077	0.2596	0.063*
C6	0.26126 (15)	0.3547 (9)	0.7954 (6)	0.0758 (13)
H6	0.2261	0.3976	0.7599	0.091*
C5	0.30623 (16)	0.4839 (7)	0.7665 (6)	0.0669 (11)
H5	0.3009	0.6125	0.7128	0.080*
C2	0.31909 (18)	0.1055 (7)	0.9206 (6)	0.0742 (13)
H2	0.3245	−0.0261	0.9694	0.089*
C8	0.47699 (16)	0.7294 (7)	0.6096 (5)	0.0598 (10)
H8A	0.5107	0.6557	0.5758	0.072*
H8B	0.4853	0.8099	0.7094	0.072*
C3	0.36470 (16)	0.2363 (7)	0.8960 (6)	0.0679 (12)
H3	0.3996	0.1943	0.9346	0.082*
C9	0.45847 (17)	0.8752 (5)	0.4737 (5)	0.0527 (9)
H9A	0.4884	0.9732	0.4482	0.063*
H9B	0.4266	0.9566	0.5121	0.063*
C13	0.2170 (2)	0.0223 (10)	0.9085 (8)	0.0951 (16)
H13A	0.1836	0.0885	0.8674	0.143*
H13B	0.2135	−0.0011	1.0262	0.143*
H13C	0.2223	−0.1105	0.8530	0.143*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O2	0.097 (2)	0.0792 (19)	0.0541 (17)	0.0001 (17)	−0.0073 (14)	0.0175 (16)
N1	0.0614 (17)	0.0478 (18)	0.0413 (15)	−0.0129 (14)	0.0013 (12)	0.0037 (14)
O1	0.105 (2)	0.117 (3)	0.0441 (16)	−0.045 (2)	−0.0064 (15)	−0.0106 (18)
C10	0.0621 (19)	0.056 (2)	0.0418 (18)	−0.0096 (18)	0.0032 (15)	0.0054 (18)
C4	0.056 (2)	0.056 (2)	0.0323 (15)	0.0001 (16)	−0.0009 (13)	0.0075 (17)
C1	0.062 (2)	0.079 (3)	0.0472 (19)	−0.016 (2)	0.0102 (17)	0.005 (2)
C12	0.061 (2)	0.046 (2)	0.056 (2)	−0.0113 (17)	0.0065 (16)	−0.002 (2)
C7	0.0619 (19)	0.050 (2)	0.0396 (18)	−0.0035 (16)	−0.0048 (16)	0.0088 (17)
C11	0.061 (2)	0.055 (2)	0.0422 (17)	−0.0058 (17)	−0.0002 (14)	−0.0092 (18)
C6	0.0438 (19)	0.100 (3)	0.084 (3)	0.006 (2)	0.003 (2)	0.005 (3)
C5	0.064 (2)	0.060 (2)	0.077 (3)	0.0036 (19)	0.003 (2)	0.021 (2)
C2	0.075 (3)	0.064 (3)	0.083 (3)	−0.020 (2)	−0.012 (2)	0.032 (3)
C8	0.064 (2)	0.067 (3)	0.048 (2)	−0.0260 (19)	−0.0126 (16)	0.010 (2)
C3	0.059 (2)	0.061 (3)	0.084 (3)	−0.0081 (19)	−0.019 (2)	0.028 (2)
C9	0.076 (2)	0.0356 (18)	0.0470 (18)	−0.0178 (18)	−0.0010 (16)	0.0040 (18)
C13	0.078 (3)	0.121 (4)	0.087 (3)	−0.041 (3)	0.016 (3)	−0.019 (3)

Geometric parameters (Å, º)

O2—C10	1.401 (5)	C12—H12B	0.9700
O2—H2A	0.8200	C11—H11A	0.9700
N1—C7	1.327 (5)	C11—H11B	0.9700
N1—C12	1.454 (5)	C6—C5	1.372 (6)
N1—C8	1.462 (4)	C6—H6	0.9300
O1—C7	1.237 (5)	C5—H5	0.9300
C10—C9	1.500 (5)	C2—C3	1.385 (5)
C10—C11	1.514 (5)	C2—H2	0.9300
C10—H10	0.9800	C8—C9	1.496 (5)
C4—C3	1.363 (6)	C8—H8A	0.9700
C4—C5	1.386 (5)	C8—H8B	0.9700
C4—C7	1.487 (5)	C3—H3	0.9300
C1—C2	1.358 (6)	C9—H9A	0.9700
C1—C6	1.373 (7)	C9—H9B	0.9700
C1—C13	1.514 (6)	C13—H13A	0.9600
C12—C11	1.509 (5)	C13—H13B	0.9600
C12—H12A	0.9700	C13—H13C	0.9600
C10—O2—H2A	109.5	C5—C6—C1	122.0 (4)
C7—N1—C12	126.1 (3)	C5—C6—H6	119.0
C7—N1—C8	121.3 (3)	C1—C6—H6	119.0
C12—N1—C8	112.6 (3)	C6—C5—C4	120.9 (4)
O2—C10—C9	108.7 (3)	C6—C5—H5	119.6
O2—C10—C11	110.4 (3)	C4—C5—H5	119.6
C9—C10—C11	110.2 (3)	C1—C2—C3	121.8 (4)
O2—C10—H10	109.1	C1—C2—H2	119.1
C9—C10—H10	109.1	C3—C2—H2	119.1
C11—C10—H10	109.1	N1—C8—C9	109.4 (3)
C3—C4—C5	117.0 (3)	N1—C8—H8A	109.8
C3—C4—C7	121.7 (3)	C9—C8—H8A	109.8
C5—C4—C7	121.2 (3)	N1—C8—H8B	109.8
C2—C1—C6	116.9 (3)	C9—C8—H8B	109.8
C2—C1—C13	121.1 (4)	H8A—C8—H8B	108.2
C6—C1—C13	122.0 (4)	C4—C3—C2	121.3 (4)
N1—C12—C11	111.1 (3)	C4—C3—H3	119.3
N1—C12—H12A	109.4	C2—C3—H3	119.3
C11—C12—H12A	109.4	C8—C9—C10	111.9 (3)
N1—C12—H12B	109.4	C8—C9—H9A	109.2
C11—C12—H12B	109.4	C10—C9—H9A	109.2
H12A—C12—H12B	108.0	C8—C9—H9B	109.2
O1—C7—N1	121.2 (3)	C10—C9—H9B	109.2
O1—C7—C4	119.7 (3)	H9A—C9—H9B	107.9
N1—C7—C4	119.0 (3)	C1—C13—H13A	109.5
C12—C11—C10	110.6 (3)	C1—C13—H13B	109.5
C12—C11—H11A	109.5	H13A—C13—H13B	109.5
C10—C11—H11A	109.5	C1—C13—H13C	109.5
C12—C11—H11B	109.5	H13A—C13—H13C	109.5
C10—C11—H11B	109.5	H13B—C13—H13C	109.5
H11A—C11—H11B	108.1
C7—N1—C12—C11	117.5 (4)	C13—C1—C6—C5	179.5 (5)
C8—N1—C12—C11	−58.2 (4)	C1—C6—C5—C4	0.5 (7)
C12—N1—C7—O1	175.6 (4)	C3—C4—C5—C6	−0.6 (6)
C8—N1—C7—O1	−9.0 (6)	C7—C4—C5—C6	−177.1 (4)
C12—N1—C7—C4	−1.3 (6)	C6—C1—C2—C3	3.5 (7)
C8—N1—C7—C4	174.1 (3)	C13—C1—C2—C3	−177.9 (5)
C3—C4—C7—O1	−74.8 (5)	C7—N1—C8—C9	−117.4 (4)
C5—C4—C7—O1	101.5 (5)	C12—N1—C8—C9	58.6 (4)
C3—C4—C7—N1	102.2 (4)	C5—C4—C3—C2	2.2 (7)
C5—C4—C7—N1	−81.6 (5)	C7—C4—C3—C2	178.7 (4)
N1—C12—C11—C10	54.7 (4)	C1—C2—C3—C4	−3.8 (8)
O2—C10—C11—C12	−173.3 (3)	N1—C8—C9—C10	−57.0 (4)
C9—C10—C11—C12	−53.1 (4)	O2—C10—C9—C8	176.3 (3)
C2—C1—C6—C5	−1.9 (7)	C11—C10—C9—C8	55.1 (5)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2A···O1i	0.82	1.97	2.741 (4)	156
C8—H8B···O1	0.97	2.33	2.740 (5)	105

Symmetry code: (i) x, y, z−1.