Crystal structure of [4-(chloro­meth­yl)phen­yl](4-hy­droxy­piperidin-1-yl)methanone

B K Revathi; D Reuben Jonathan; K Kalai Sevi; K Dhanalakshmi; G Usha

doi:10.1107/S2056989015016096

. 2015 Sep 12;71(Pt 10):o703–o704. doi: 10.1107/S2056989015016096

Crystal structure of [4-(chloromethyl)phenyl](4-hydroxypiperidin-1-yl)methanone

B K Revathi ^a, D Reuben Jonathan ^b, K Kalai Sevi ^c, K Dhanalakshmi ^d, G Usha ^a,^*

PMCID: PMC4647401 PMID: 26594432

Abstract

The title compound, C₁₃H₁₆ClNO₂, crystallized with two independent molecules in the asymmetric unit (A and B). The piperidinol ring in molecule B is disordered over two positions with a site occupancy ratio of 0.667 (5):0.333 (5). In both molecules these rings have a chair conformation, including the minor component in molecule B. Their mean planes are inclined to the benzene ring by 45.57 (13)° in molecule A, and by 50.5 (4)° for the major component of the piperidine ring in molecule B. In the crystal, the individual molecules are linked by O—H⋯O hydrogen bonds, forming chains of A and B molecules along the [100] direction. The chains are interlinked by C—H⋯O hydrogen bonds, forming ribbons.

Keywords: crystal structure, piperidine derivative, hydrogen bonding

Related literature

For the synthesis see: Revathi et al. (2015 ▸). For the biological activity of piperidine derivatives, see: Daly et al. (1986 ▸); Fodor et al. (1985 ▸); Campfield et al. (1995 ▸); Kozikowski et al. (1998 ▸); Brau et al. (2000 ▸); Bolzani et al. (1995 ▸); Gulluoglu et al. (2007 ▸). For related structures see: Revathi et al. (2015 ▸); Prathebha et al. (2015 ▸).

Experimental

Crystal data

C₁₃H₁₆ClNO₂
M _r = 253.72
Triclinic,
a = 8.4131 (3) Å
b = 9.6211 (4) Å
c = 15.6780 (6) Å
α = 80.917 (3)°
β = 89.240 (2)°
γ = 88.395 (2)°
V = 1252.57 (8) Å³
Z = 4
Mo Kα radiation
μ = 0.29 mm⁻¹
T = 293 K
0.35 × 0.30 × 0.25 mm

Data collection

Bruker Kappa APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2004 ▸) T _min = 0.902, T _max = 0.943
28447 measured reflections
4415 independent reflections
3411 reflections with I > 2σ(I)
R _int = 0.027

Refinement

R[F ² > 2σ(F ²)] = 0.045
wR(F ²) = 0.128
S = 1.05
4415 reflections
371 parameters
111 restraints
H-atom parameters constrained
Δρ_max = 0.45 e Å⁻³
Δρ_min = −0.62 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: SIR92 (Altomare et al., 1993 ▸); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015 ▸); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▸) and Mercury (Bruno et al., 2002 ▸); software used to prepare material for publication: SHELXL2014.

Supplementary Material

Crystal structure: contains datablock(s) I, New_Global_Publ_Block. DOI: 10.1107/S2056989015016096/bg2567sup1.cif

e-71-0o703-sup1.cif^{(1.1MB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015016096/bg2567Isup2.hkl

e-71-0o703-Isup2.hkl^{(351.4KB, hkl)}

Click here for additional data file.^{(5KB, cml)}

Supporting information file. DOI: 10.1107/S2056989015016096/bg2567Isup3.cml

Click here for additional data file.^{(1.2MB, tif)}

. DOI: 10.1107/S2056989015016096/bg2567fig1.tif

The molecular structure of the title compound (left: molecula A; right: molecule B), with displacement ellipsoids drawn at the 30% probability level.

Click here for additional data file.^{(2.2MB, tif)}

. DOI: 10.1107/S2056989015016096/bg2567fig2.tif

The packing of the molecules in the crystal structure. The dashed lines indicate the hydrogen bonds.

CCDC reference: 1421009

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

Table 1. Hydrogen-bond geometry (, ).

DHA	DH	HA	D A	DHA
O2H2AO1ⁱ	0.82	2.18	2.789(2)	132
O4H4O3ⁱⁱ	0.82	2.13	2.793(3)	138
C11H11BO3ⁱⁱⁱ	0.97	2.60	3.522(3)	160
C26H26AO2^iv	0.97	2.59	3.494(4)	154

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) .

Acknowledgments

The authors thank the DST–FIST, Central Instrumentation Facility, Queen Mary’s College, Chennai-4, for the computing facility and the SAIF, IIT, Madras, for the X-ray data-collection facility.

supplementary crystallographic information

S1. Comment

Many piperidine containing compounds possess remarkable biological and medicinal properties (Daly et al., (1986); Fodor et al., (1985)). Among their remarkable properties, they show appreciable effect on plasma glucose level (Campfield et al., (1995)), insulin normalization, therapeutics on cocaine abuse (Kozikowski et al., (1998)). Piperidine also participates in amny local anesthetics, such as mepivacaine, ropivacaine, and bupivacaine, extensively used in clinical practice (Brau et al., (2000); Bolzani et al., (1995)). Piperidine derivatives are found to exhibit pharmacological activity and form a vital part of the molecular structures of important drugs such as raloxifene and minoxidil. Selective inhibition of a number of enzymes has rendered piperidine alkaloids as important paraphernalia in the study of biochemical pathways (Gulluoglu et al., (2007).

The title compound, C₁₃H₁₆ClNO₂, (I), crystallizes with two molecules in the asymmetric unit: A ( Fig1, left) and B (Fig 1, right) . Bond lengths and angles are comparable with literature values. C—N distances of the piperdine ring in molecule A C8—C12/N1 & in molecule B C21—C25/N2, are in the range 1.459 (3)- 1.462 (3) Å and are in good agreement with values of a similar reported structure (Revathi et al., (2015)). The C=O distances in molecules A & B are [1.235 (3) and 1.233 (3) Å], respectively, and is comparable with the previously reported value(Prathebha et al., (2015). In the molecule A, the dihedral angle between piperdine ring and the phenyl ring 47.22 (1)°, indicates the bisectional orientation of the phenylring. The bond angles around the N1 and N2 atoms [358.85 (2)° and 359.47 (2)°, respectively], shows sp² hybridization of the atoms. The piperidine ring of the molecule A, adopts a chair conformation with puckering parameters of q2 = 0.019 (2) Å, φ2 = -58.74° q3 = -0.567 (3) Å, QT= 0.567 (3) Å and θ2 = 178.03 (2)°.

In the crystal packing the molecules form chains running along the diagonal of 'bc' plane through O—H···O type hydrogen bonds. These chains are further inter linked through C—H···O type hydrogen bonds to form molecular ribbons (Fig. 2).

S2. Experimental

The title compound was synthesized following a publish procedure (Revathi et al., (2015)). In a 250 ml roundbottomed flask 120 ml of ethylmethylketone 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. Then 4-chloromethyl benzoylchloride(0.04 mol) was added and the reaction mixture was stirred at room temperature for ca 2 h. A white precipitate of triethylammoniumchloride was formed. It was filtered and the filtrate was evaporated to give the crude product. It was recrystallized twice from ethylmethylketone (yield: 82%) giving colourless block-like crystals of the title compound.