1-[4-(4-Hy­droxy­phen­yl)piperazin-1-yl]ethanone

Channappa N Kavitha; Jerry P Jasinski; Brian J Anderson; H S Yathirajan; Manpreet Kaur

doi:10.1107/S1600536813028031

. 2013 Oct 19;69(Pt 11):o1671. doi: 10.1107/S1600536813028031

1-[4-(4-Hydroxyphenyl)piperazin-1-yl]ethanone

Channappa N Kavitha ^a, Jerry P Jasinski ^b,^*, Brian J Anderson ^b, H S Yathirajan ^a, Manpreet Kaur ^a

PMCID: PMC3884329 PMID: 24454105

Abstract

In the title compound, C₁₂H₁₆N₂O₂, the piperazine ring has a chair conformation. The dihedral angle between the mean planes of the benzene ring and the acetyl group is 48.7 (1)°. In the crystal, molecules are linked via O—H⋯O hydrogen bonds, forming chains propagating along [010].

Related literature

For the biological activity of piperazine derivatives, see: Bogatcheva et al. (2006 ▶); Brockunier et al. (2004 ▶); Elliott (2011 ▶); Kharb et al. (2012 ▶). For the crystal structures of related compounds, see: Dayananda et al. (2012 ▶); Kavitha et al. (2013a ▶,b ▶); Peeters et al. (1979 ▶, 2004 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶). For standard bond lengths, see: Allen et al. (1987 ▶). graphic file with name e-69-o1671-scheme1.jpg

Experimental

Crystal data

C₁₂H₁₆N₂O₂
M _r = 220.27
Monoclinic,
a = 6.13183 (19) Å
b = 12.0106 (4) Å
c = 14.8704 (5) Å
β = 94.025 (3)°
V = 1092.46 (6) Å³
Z = 4
Cu Kα radiation
μ = 0.75 mm⁻¹
T = 173 K
0.48 × 0.46 × 0.32 mm

Data collection

Agilent Xcalibur (Eos, Gemini) diffractometer
Absorption correction: multi-scan (CrysAlis PRO and CrysAlis RED; Agilent, 2012 ▶) T _min = 0.833, T _max = 1.000
6224 measured reflections
2134 independent reflections
1944 reflections with I > 2σ(I)
R _int = 0.025

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.113
S = 1.07
2134 reflections
147 parameters
H-atom parameters constrained
Δρ_max = 0.22 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Data collection: CrysAlis PRO (Agilent, 2012 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis RED (Agilent, 2012 ▶); program(s) used to solve structure: SUPERFLIP (Palatinus & Chapuis, 2007 ▶); program(s) used to refine structure: SHELXL2012 (Sheldrick, 2008 ▶); molecular graphics: OLEX2 (Dolomanov et al., 2009 ▶); software used to prepare material for publication: OLEX2.

Supplementary Material

Crystal structure: contains datablock(s) I. DOI: 10.1107/S1600536813028031/su2656sup1.cif

e-69-o1671-sup1.cif^{(20.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813028031/su2656Isup2.hkl

e-69-o1671-Isup2.hkl^{(117.4KB, hkl)}

Click here for additional data file.^{(4.7KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813028031/su2656Isup3.cml

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯O1ⁱ	0.82	1.88	2.6953 (14)	170

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Symmetry code: (i) Inline graphic .

Acknowledgments

CNK thanks the University of Mysore for research facilities and is also grateful to the Principal, Maharani’s Science College for Women, Mysore, for permission to carry out research. JPJ acknowledges the NSF–MRI program (grant No. CHE-1039027) for funds to purchase the X-ray diffractometer.

supplementary crystallographic information

1. Comment

The title compound is used to synthesize ketoconazole which is a antifungal agent. A valuable insight into recent advances on antimicrobial activity of piperazine derivatives has been reported by (Kharb et al., 2012). Many currently notable drugs contain a piperazine ring as part of their molecular structure. Piperazines are also among the most important building blocks in today's drug discovery and are found in biologically active compounds across a number of different therapeutic areas (Brockunier et al., 2004; Bogatcheva et al., 2006). A review on the current pharmacological and toxicological information for piperazine derivatives is described (Elliott, 2011). The crystal structures of some related compounds, viz., cis-1-acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-1-imidazolyl methyl)-1,3-dioxolan-4-yl]methoxy}phenyl) piperazine: ketoconazole. A crystal structure with disorder (Peeters et al., 1979), (+)-cis-1-acetyl-4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H- imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine [(2R,4S)-(+)-ketoconazole] (Peeters et al., 2004), 1-{4-[bis (4-fluorophenyl)methyl]piperazin-1-yl}ethanone (Dayananda et al. , 2012), cinnarizinium bis(p-toluenesulfonate)dihydrate (Kavitha et al., 2013a) and flunarizinium hydrogen maleate (Kavitha et al., 2013b) have been reported. In view of the importance of the title compound this paper reports its crystal structure.

The molecular structure of the title compound is illustrated in Fig. 1. The piperazine ring has a chair conformation with puckering parameters (Cremer & Pople, 1975), Q, θ, and φ = 0.5661 (13) Å, 174.05 (12)° and 0.9 (13)°, respectively. The dihedral angle between the mean planes of the benzene ring (C6-C11) and the acetyl group (N1/C1/C12/O1) is 48.7 (1)°. Bond lengths are in normal ranges (Allen et al., 1987).

In the crystal, O—H···O hydrogen bonds (Table 1) are observed which link the molecules into chains along [0 1 0], as shown in Fig. 2.

2. Experimental

The title compound was purchased from Sigma-Aldrich and was recrystallized from ethanol by slow evaporation to give irregular block-like colourless crystals (M.p. = 453 K).