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

Kavitha, C.N.; Jasinski, J.P.; Anderson, B.J.; Yathirajan, H.S.; Kaur, M.

doi:10.1107/S1600536813028031

organic compounds

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ISSN: 2056-9890

Volume 69| Part 11| November 2013| Page o1671

doi:10.1107/S1600536813028031

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

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

^aDepartment of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India, and ^bDepartment of Chemistry, Keene State College, 229 Main Street, Keene, NH 03435-2001, USA
^*Correspondence e-mail: jjasinski@keene.edu

(Received 9 October 2013; accepted 12 October 2013; online 19 October 2013)

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].

CCDC reference: 966190

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 ).

Experimental

Crystal data

C₁₂H₁₆N₂O₂
M_r = 220.27
Monoclinic, P 2₁ /c
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[F² > 2σ(F²)] = 0.041
wR(F²) = 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

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
Symmetry code: (i) x, y+1, z.

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.

Supporting information

CCDC reference: 966190

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

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

Supporting information file. DOI: 10.1107/S1600536813028031/su2656Isup3.cml

checkCIF report

Comment top

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.

Related literature top

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).

Experimental top

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).

Computing details top

Data collection: CrysAlis PRO (Agilent, 2012); cell refinement: CrysAlis PRO (Agilent, 2012); 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 (Dolomanov et al., 2009).

Figures top

	Fig. 1. The molecular structure of the title molecule, with atom labelling. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. A view along the a axis of the crystal packing of the title compound. The O—H···O hydrogen bonds, linking the molecules into chains along [0 1 0], are shown as dashed lines (see Table 1 for details; H atoms not involved in hydrogen bonding have been omitted for clarity).

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

Crystal data top

C₁₂H₁₆N₂O₂	F(000) = 472
M_r = 220.27	D_x = 1.339 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54184 Å
a = 6.13183 (19) Å	Cell parameters from 3201 reflections
b = 12.0106 (4) Å	θ = 3.7–72.1°
c = 14.8704 (5) Å	µ = 0.75 mm⁻¹
β = 94.025 (3)°	T = 173 K
V = 1092.46 (6) Å³	Block, colourless
Z = 4	0.48 × 0.46 × 0.32 mm

Data collection top

Agilent Xcalibur (Eos, Gemini) diffractometer	2134 independent reflections
Radiation source: Enhance (Cu) X-ray Source	1944 reflections with I > 2σ(I)
Detector resolution: 16.0416 pixels mm^-1	R_int = 0.025
ω scans	θ_max = 72.3°, θ_min = 4.7°
Absorption correction: multi-scan (CrysAlis PRO and CrysAlis RED; Agilent, 2012)	h = −7→5
T_min = 0.833, T_max = 1.000	k = −14→14
6224 measured reflections	l = −17→18

Refinement top

Refinement on F²	0 restraints
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.041	H-atom parameters constrained
wR(F²) = 0.113	w = 1/[σ²(F_o²) + (0.063P)² + 0.2496P] where P = (F_o² + 2F_c²)/3
S = 1.07	(Δ/σ)_max < 0.001
2134 reflections	Δρ_max = 0.22 e Å⁻³
147 parameters	Δρ_min = −0.18 e Å⁻³

Crystal data top

C₁₂H₁₆N₂O₂	V = 1092.46 (6) Å³
M_r = 220.27	Z = 4
Monoclinic, P2₁/c	Cu Kα radiation
a = 6.13183 (19) Å	µ = 0.75 mm⁻¹
b = 12.0106 (4) Å	T = 173 K
c = 14.8704 (5) Å	0.48 × 0.46 × 0.32 mm
β = 94.025 (3)°

Data collection top

Agilent Xcalibur (Eos, Gemini) diffractometer	2134 independent reflections
Absorption correction: multi-scan (CrysAlis PRO and CrysAlis RED; Agilent, 2012)	1944 reflections with I > 2σ(I)
T_min = 0.833, T_max = 1.000	R_int = 0.025
6224 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.041	0 restraints
wR(F²) = 0.113	H-atom parameters constrained
S = 1.07	Δρ_max = 0.22 e Å⁻³
2134 reflections	Δρ_min = −0.18 e Å⁻³
147 parameters

Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.76473 (18)	−0.03376 (8)	0.41180 (7)	0.0420 (3)
O2	0.92639 (18)	0.80536 (7)	0.30904 (7)	0.0375 (3)
H2	0.8626	0.8514	0.3383	0.056*
N1	0.62601 (17)	0.13923 (9)	0.41758 (7)	0.0273 (3)
N2	0.71764 (16)	0.37192 (8)	0.41491 (7)	0.0244 (3)
C1	0.6095 (2)	0.03108 (10)	0.39631 (8)	0.0285 (3)
C2	0.44858 (19)	0.22001 (10)	0.40349 (9)	0.0299 (3)
H2A	0.3914	0.2384	0.4608	0.036*
H2B	0.3309	0.1879	0.3649	0.036*
C3	0.5312 (2)	0.32459 (10)	0.36038 (9)	0.0305 (3)
H3A	0.5754	0.3072	0.3006	0.037*
H3B	0.4143	0.3791	0.3542	0.037*
C4	0.89577 (19)	0.29095 (10)	0.42176 (8)	0.0262 (3)
H4A	1.0203	0.3222	0.4569	0.031*
H4B	0.9407	0.2738	0.3620	0.031*
C5	0.8215 (2)	0.18508 (10)	0.46652 (9)	0.0290 (3)
H5A	0.9381	0.1304	0.4680	0.035*
H5B	0.7897	0.2012	0.5282	0.035*
C6	0.77423 (19)	0.48149 (10)	0.38735 (8)	0.0238 (3)
C7	0.6271 (2)	0.56832 (10)	0.39795 (8)	0.0276 (3)
H7	0.4959	0.5540	0.4235	0.033*
C8	0.6738 (2)	0.67575 (10)	0.37087 (8)	0.0293 (3)
H8	0.5713	0.7319	0.3766	0.035*
C9	0.8717 (2)	0.70046 (10)	0.33537 (8)	0.0275 (3)
C10	1.0194 (2)	0.61483 (11)	0.32474 (9)	0.0315 (3)
H10	1.1523	0.6299	0.3008	0.038*
C11	0.9702 (2)	0.50671 (10)	0.34968 (9)	0.0290 (3)
H11	1.0700	0.4500	0.3411	0.035*
C12	0.3937 (2)	−0.01011 (11)	0.35382 (10)	0.0366 (3)
H12A	0.4010	−0.0892	0.3450	0.055*
H12B	0.3631	0.0260	0.2967	0.055*
H12C	0.2796	0.0067	0.3927	0.055*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0495 (6)	0.0251 (5)	0.0499 (6)	0.0119 (4)	−0.0068 (5)	−0.0033 (4)
O2	0.0524 (6)	0.0219 (5)	0.0390 (5)	−0.0023 (4)	0.0087 (4)	0.0006 (4)
N1	0.0268 (5)	0.0210 (5)	0.0336 (6)	0.0034 (4)	−0.0010 (4)	−0.0004 (4)
N2	0.0215 (5)	0.0200 (5)	0.0314 (5)	0.0030 (4)	−0.0008 (4)	0.0000 (4)
C1	0.0396 (7)	0.0221 (6)	0.0238 (6)	0.0032 (5)	0.0016 (5)	0.0015 (4)
C2	0.0229 (6)	0.0235 (6)	0.0431 (7)	0.0027 (5)	−0.0002 (5)	−0.0042 (5)
C3	0.0257 (6)	0.0229 (6)	0.0415 (7)	0.0045 (5)	−0.0071 (5)	0.0006 (5)
C4	0.0226 (6)	0.0232 (6)	0.0323 (6)	0.0048 (5)	−0.0021 (5)	0.0008 (5)
C5	0.0281 (6)	0.0233 (6)	0.0348 (6)	0.0034 (5)	−0.0045 (5)	0.0023 (5)
C6	0.0259 (6)	0.0209 (6)	0.0239 (6)	0.0026 (4)	−0.0028 (4)	−0.0013 (4)
C7	0.0286 (6)	0.0249 (6)	0.0294 (6)	0.0048 (5)	0.0037 (5)	−0.0004 (5)
C8	0.0363 (7)	0.0226 (6)	0.0290 (6)	0.0077 (5)	0.0023 (5)	−0.0015 (5)
C9	0.0383 (7)	0.0204 (6)	0.0233 (6)	−0.0009 (5)	−0.0023 (5)	−0.0011 (4)
C10	0.0274 (6)	0.0299 (7)	0.0371 (7)	−0.0019 (5)	0.0024 (5)	0.0008 (5)
C11	0.0246 (6)	0.0235 (6)	0.0386 (7)	0.0041 (5)	0.0013 (5)	−0.0006 (5)
C12	0.0500 (8)	0.0229 (6)	0.0354 (7)	−0.0018 (6)	−0.0080 (6)	−0.0012 (5)

Geometric parameters (Å, º) top

O1—C1	1.2387 (16)	C4—C5	1.5200 (17)
O2—H2	0.8200	C5—H5A	0.9700
O2—C9	1.3681 (15)	C5—H5B	0.9700
N1—C1	1.3391 (16)	C6—C7	1.3950 (17)
N1—C2	1.4618 (15)	C6—C11	1.3943 (18)
N1—C5	1.4651 (16)	C7—H7	0.9300
N2—C3	1.4688 (15)	C7—C8	1.3875 (18)
N2—C4	1.4607 (14)	C8—H8	0.9300
N2—C6	1.4284 (15)	C8—C9	1.3888 (19)
C1—C12	1.5096 (18)	C9—C10	1.3869 (18)
C2—H2A	0.9700	C10—H10	0.9300
C2—H2B	0.9700	C10—C11	1.3896 (18)
C2—C3	1.5136 (18)	C11—H11	0.9300
C3—H3A	0.9700	C12—H12A	0.9600
C3—H3B	0.9700	C12—H12B	0.9600
C4—H4A	0.9700	C12—H12C	0.9600
C4—H4B	0.9700

C9—O2—H2	109.5	N1—C5—H5A	109.5
C1—N1—C2	124.54 (11)	N1—C5—H5B	109.5
C1—N1—C5	121.83 (10)	C4—C5—H5A	109.5
C2—N1—C5	113.35 (10)	C4—C5—H5B	109.5
C4—N2—C3	109.27 (9)	H5A—C5—H5B	108.0
C6—N2—C3	113.18 (9)	C7—C6—N2	118.97 (11)
C6—N2—C4	115.97 (9)	C11—C6—N2	123.30 (10)
O1—C1—N1	121.45 (13)	C11—C6—C7	117.74 (11)
O1—C1—C12	120.76 (12)	C6—C7—H7	119.5
N1—C1—C12	117.78 (11)	C8—C7—C6	120.95 (12)
N1—C2—H2A	109.6	C8—C7—H7	119.5
N1—C2—H2B	109.6	C7—C8—H8	119.6
N1—C2—C3	110.09 (10)	C7—C8—C9	120.83 (11)
H2A—C2—H2B	108.2	C9—C8—H8	119.6
C3—C2—H2A	109.6	O2—C9—C8	122.96 (11)
C3—C2—H2B	109.6	O2—C9—C10	118.35 (12)
N2—C3—C2	110.98 (10)	C10—C9—C8	118.68 (11)
N2—C3—H3A	109.4	C9—C10—H10	119.8
N2—C3—H3B	109.4	C9—C10—C11	120.45 (12)
C2—C3—H3A	109.4	C11—C10—H10	119.8
C2—C3—H3B	109.4	C6—C11—H11	119.3
H3A—C3—H3B	108.0	C10—C11—C6	121.31 (11)
N2—C4—H4A	109.7	C10—C11—H11	119.3
N2—C4—H4B	109.7	C1—C12—H12A	109.5
N2—C4—C5	109.99 (10)	C1—C12—H12B	109.5
H4A—C4—H4B	108.2	C1—C12—H12C	109.5
C5—C4—H4A	109.7	H12A—C12—H12B	109.5
C5—C4—H4B	109.7	H12A—C12—H12C	109.5
N1—C5—C4	110.90 (10)	H12B—C12—H12C	109.5

O2—C9—C10—C11	−179.37 (11)	C4—N2—C6—C7	−166.26 (11)
N1—C2—C3—N2	−56.20 (14)	C4—N2—C6—C11	14.00 (16)
N2—C4—C5—N1	56.23 (13)	C5—N1—C1—O1	−4.88 (19)
N2—C6—C7—C8	−179.02 (11)	C5—N1—C1—C12	174.25 (11)
N2—C6—C11—C10	−179.29 (11)	C5—N1—C2—C3	52.56 (14)
C1—N1—C2—C3	−133.46 (13)	C6—N2—C3—C2	−168.28 (10)
C1—N1—C5—C4	132.86 (12)	C6—N2—C4—C5	170.42 (10)
C2—N1—C1—O1	−178.37 (12)	C6—C7—C8—C9	−2.28 (19)
C2—N1—C1—C12	0.76 (18)	C7—C6—C11—C10	0.97 (19)
C2—N1—C5—C4	−52.98 (14)	C7—C8—C9—O2	−178.98 (11)
C3—N2—C4—C5	−60.23 (13)	C7—C8—C9—C10	2.06 (19)
C3—N2—C6—C7	66.31 (14)	C8—C9—C10—C11	−0.36 (19)
C3—N2—C6—C11	−113.43 (13)	C9—C10—C11—C6	−1.2 (2)
C4—N2—C3—C2	60.86 (13)	C11—C6—C7—C8	0.74 (18)

Hydrogen-bond geometry (Å, º) top

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

Symmetry code: (i) x, y+1, z.

Hydrogen-bond geometry (Å, º) top

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

Symmetry code: (i) x, y+1, z.

Acknowledgements

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.

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