research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 72| Part 2| February 2016| Pages 269-272
doi:10.1107/S2056989016000992

Crystal structure of 3-{[4-(2-meth­­oxy­phen­yl)piperazin-1-yl]meth­yl}-5-(thio­phen-2-yl)-1,3,4-oxa­diazole-2(3H)-thione

CROSSMARK_Color_square_no_text.svg
Monirah A. Al-Alshaikh,a Hatem A. Abuelizz,b Ali A. El-Emam,b‡ Mohammed S. M. Abdelbakyc and Santiago Garcia-Grandac*

aDepartment of Chemistry, College of Sciences, King Saud University, Riyadh 11451, Saudi Arabia, bDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia, and cDepartment of Physical and Analytical Chemistry, Faculty of Chemistry, Oviedo University-CINN, Oviedo 33006, Spain
*Correspondence e-mail: sgg@uniovi,es

Edited by H. Stoeckli-Evans, University of Neuchâtel, Switzerland (Received 3 January 2016; accepted 17 January 2016; online 30 January 2016)

The title compound, C18H20N4O2S2, is a new 1,3,4-oxa­diazole and a key pharmacophore of several biologically active agents. It is composed of a meth­yl(thio­phen-2-yl)-1,3,4-oxa­diazole-2(3H)-thione moiety linked to a 2-meth­oxy­phenyl unit via a piperazine ring that has a chair conformation. The thio­phene ring mean plane lies almost in the plane of the oxa­diazole ring, with a dihedral angle of 4.35 (9)°. The 2-meth­oxy­phenyl ring is almost normal to the oxa­diazole ring, with a dihedral angle of 84.17 (10)°. In the crystal, mol­ecules are linked by weak C—H⋯S hydrogen bonds and C—H⋯π inter­actions, forming layers parallel to the bc plane. The layers are linked via weak C—H⋯O hydrogen bonds and slipped parallel π–π inter­actions [inter­centroid distance = 3.6729 (10) Å], forming a three-dimensional structure. The thio­phene ring has an approximate 180° rotational disorder about the bridging C—C bond.

CCDC reference: 1447823

1. Chemical context

1,3,4-Oxa­diazole derivatives are structural motifs of particular value in material sciences (Zhang et al., 2011[Zhang, Y., Zuniga, C., Kim, S.-J., Cai, D., Barlow, S., Salman, S., Coropceanu, V., Brédas, J.-L., Kippelen, B. & Marder, S. (2011). Chem. Mater. 23, 4002-4015.]) and agrochemistry (Shi et al., 2001[Shi, W., Qian, X., Zhang, R. & Song, G. (2001). J. Agric. Food Chem. 49, 124-130.]; Milinkevich et al., 2009[Milinkevich, K. A., Yoo, C. L., Sparks, T. C., Lorsbach, B. A. & Kurth, M. J. (2009). Bioorg. Med. Chem. Lett. 19, 5796-5798.]; Li et al., 2014[Li, P., Shi, L., Yang, X., Yang, L., Chen, X.-W., Wu, F., Shi, Q.-C., Xu, W.-M., He, M., Hu, D.-Y. & Song, B.-A. (2014). Bioorg. Med. Chem. Lett. 24, 1677-1680.]). In addition, they occupy a unique situation in the field of medicinal chemistry as pharmacophores possessing diverse pharmacological activities including anti­bacterial (Ogata et al., 1971[Ogata, M., Atobe, H., Kushida, H. & Yamamoto, K. (1971). J. Antibiot. 24, 443-451.]; Rane et al., 2012[Rane, R. A., Gutte, S. W. & Sahu, N. U. (2012). Bioorg. Med. Chem. Lett. 22, 6429-6432.]; Al-Omar, 2010[Al-Omar, M. A. (2010). Molecules, 15, 502-514.]), anti­cancer (Pinna et al., 2009[Pinna, G. A., Murineddu, G., Murruzzu, C., Zuco, V., Zunino, F., Cappelletti, G., Artali, R., Cignarella, G., Solano, L. & Villa, S. (2009). ChemMedChem, 4, 998-1009.]; Gamal El-Din et al., 2015[Gamal El-Din, M. M., El-Gamal, M. I., Abdel-Maksoud, M. S., Yoo, K. H. & Oh, C.-H. (2015). Eur. J. Med. Chem. 90, 45-52.]; Zhang et al., 2014[Zhang, K., Wang, P., Xuan, L.-N., Fu, X.-Y., Jing, F., Li, S., Liu, Y.-M. & Chen, B.-Q. (2014). Bioorg. Med. Chem. Lett. 24, 5154-5156.]; Du et al., 2013[Du, Q.-R., Li, D.-D., Pi, Y.-Z., Li, J.-R., Sun, J., Fang, F., Zhong, W.-Q., Gong, H.-B. & Zhu, H.-L. (2013). Eur. J. Med. Chem. 21, 2286-2297.]), anti­viral (Summa et al., 2008[Summa, V., Petrocchi, A., Bonelli, F., Crescenzi, B., Donghi, M., Ferrara, M., Fiore, F., Gardelli, C., Gonzalez Paz, O., Hazuda, D. J., Jones, P., Kinzel, O., Laufer, R., Monteagudo, E., Muraglia, E., Nizi, E., Orvieto, F., Pace, P., Pescatore, G., Scarpelli, R., Stillmock, K., Witmer, M. V. & Rowley, M. (2008). J. Med. Chem. 51, 5843-5855.]; Wu et al., 2015[Wu, W., Chen, Q., Tai, A., Jiang, G. & Ouyang, G. (2015). Bioorg. Med. Chem. Lett. 25, 2243-2246.]; El-Emam et al., 2004[El-Emam, A. A., Al-Deeb, O. A., Al-Omar, M. A. & Lehmann, J. (2004). Bioorg. Med. Chem. 12, 5107-5113.]), anti­hypertensive (Vardan et al., 1983[Vardan, S., Smulyan, H., Mookherjee, S. & Eich, R. (1983). Clin. Pharmacol. Ther. 34, 290-296.]; Schlecker & Thieme, 1988[Schlecker, R. & Thieme, P. C. (1988). Tetrahedron, 44, 3289-3294.]), anti-inflammatory (Bansal et al., 2014[Bansal, S., Bala, M., Suthar, S. K., Choudhary, S., Bhattacharya, S., Bhardwaj, V., Singla, S. & Joseph, A. (2014). Eur. J. Med. Chem. 80, 167-174.]; Kadi et al., 2007[Kadi, A. A., El-Brollosy, N. R., Al-Deeb, O. A., Habib, E. E., Ibrahim, T. M. & El-Emam, A. A. (2007). Eur. J. Med. Chem. 42, 235-242.]) and anti-oxidant (Ma et al., 2013[Ma, L., Xiao, Y., Li, C., Xie, Z.-L., Li, Z.-L., Wang, Y.-T., Ma, H.-T., Zhu, H.-L., Wang, M.-H. & Ye, Y.-H. (2013). Bioorg. Med. Chem. 21, 6763-6770.]) activities. In continuation to our previous studies on 1,3,4-oxa­diazo­les (El-Emam et al., 2012[El-Emam, A. A., El-Brollosy, N. R., Attia, M. I., Said-Abdelbaky, M. & García-Granda, S. (2012). Acta Cryst. E68, o2172-o2173.]), we report herein on the synthesis and crystal structure of the title compound.

[Scheme 1]

2. Structural commentary

The title compound, Fig. 1[link], is composed of a meth­yl(thio­phen-2-yl)-1,3,4-oxa­diazole-2(3H)-thione moiety linked to a 2-meth­oxy­phenyl unit via a bridging piperazine ring. The mol­ecule is V-shaped with the mean plane of the piperazine ring, that has a chair conformation, making dihedral angles of 51.2 (1) and 77.8 (1)° with the 2-meth­oxy­phenyl ring and the oxa­diazole ring, respectively. The thio­phene ring mean plane lies almost in the plane of the oxa­diazole ring, with a dihedral angle of 4.35 (9)°. The thio­phene ring has an approximate 180° rotational disorder about the bridging C14—C15 bond.

[Figure 1]
Figure 1
The mol­ecular structure of the title compound, showing the atom-labelling scheme and displacement ellipsoids at the 50% probability level. The thio­phene ring has an approximate 180° rotational disorder about the bridging C—C bond.

3. Supra­molecular features

In the crystal, mol­ecules are linked by weak C—H⋯S hydrogen bonds and C—H⋯π inter­actions, forming layers in the bc plane (Table 1[link] and Fig. 2[link]). The layers are linked via C—H⋯O hydrogen bonds and slipped parallel π–π inter­actions [Cg3⋯ Cg1i = 3.6729 (10) Å, inter-planar distance = 3.4757 (7) Å, slippage = 0.967 Å; Cg1 and Cg3 are the centroids of the S2A/C15/C16A/C17/C18 and O1/ N3/N4/C13/C14 rings, respectively; symmetry code (i): −x + 2, −y + 1, −z + 2], forming a three-dimensional structure (Table 1[link] and Fig. 2[link]).

Table 1
Hydrogen-bond geometry (Å, °)

Cg1 is the centroid of the S2A/C15/C16A/C17/C18 ring.
D—H⋯A D—H H⋯A D⋯A D—H⋯A
C12—H12A⋯S1i 0.97 2.95 3.860 (2) 157
C17—H17⋯O1ii 0.93 2.69 3.475 (2) 143
C5—H5⋯Cg1iii 0.93 2.95 3.660 (2) 135
Symmetry codes: (i) [x, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]; (ii) [-x+2, y+{\script{1\over 2}}, -z+{\script{5\over 2}}]; (iii) -x+1, -y+1, -z+2.
[Figure 2]
Figure 2
Crystal packing of the title compound, viewed along the b axis, showing the C—H⋯S and C—H⋯O hydrogen bonds (Table 1[link]) as dashed lines. Only H atoms involved in inter­molecular inter­actions have been included.

4. Database survey

A search of the Cambridge Structural Database (Version 5.37, last update November 2015; Groom & Allen, 2014[Groom, C. R. & Allen, F. H. (2014). Angew. Chem. Int. Ed. 53, 662-671.]) for the 3-methyl-5-(thio­phen-2-yl)-1,3,4-oxa­diazole-2(3H)-thione moiety of the title compound gave three hits. Two of these compounds also contain a substituted piperazine ring, namely 3-[(4-phenyl­piperazin-1-yl)meth­yl]-5-(2-thien­yl)-1,3,4-oxadiazole-2(3H)-thione (IDOBUA; El-Emam et al., 2013[El-Emam, A. A., Al-Omar, M. A., Al-Obaid, A.-R. M., Ng, S. W. & Tiekink, E. R. T. (2013). Acta Cryst. E69, o684.]) and 3-[(4-benzyl­piperazin-1-yl)meth­yl]-5-(thio­phen-2-yl)-2,3-dihydro-1,3,4-oxa­diazole-2-thione (VUBYUO; Al-Omary et al., 2015[Al-Omary, F. A. M., El-Emam, A. A., Ghabbour, H. A., Chidan Kumar, C. S., Quah, C. K. & Fun, H.-K. (2015). Acta Cryst. E71, o175-o176.]). In both of these mol­ecules, the conformation is very similar to that of the title compound.

5. Synthesis and crystallization

To a solution of 5-(thio­phen-2-yl)-1,3,4-oxa­diazole-2-thiol (920 mg, 5 mmol), in ethanol (15 ml), 1-(2-meth­oxy­phen­yl)piperazine (960 mg, 5 mmol) and 37% formaldehyde solution (1.0 ml) were added and the mixture was stirred at room temperature for 3 h and then allowed to stand overnight at room temperature. The precipitated crude product was filtered, washed with cold ethanol, dried, and crystallized from ethanol to yield the title compound as pale-yellow prismatic crystals(yield 1.67 g, 86%; m.p. 419–421 K). Single crystals suitable for X-ray analysis were obtained by slow evaporation of a CHCl3:EtOH solution (1:1; 15 ml) at room temperature. 1H NMR (CDCl3, 500.13 MHz): δ 3.10 (s, 8H, piperazine-H), 3.85 (s, 3H, OCH3), 5.15 (s, 2H, CH2), 6.85–6.87 (m, 1H, Ar-H), 6.92–6.95 (m, 2H, Ar-H), 7.01–7.03 (m, 1H, Ar-H), 7.18 (t, 1H, thio­phene-H, J = 4.5 Hz), 7.59 (d, 1H, thio­phene-H, J = 4.5 Hz), 7.75 (d, 1H, thio­phene-H, J = 4.5 Hz). 13C NMR (CDCl3, 125.76 MHz): δ 50.43, 50.64 (piperazine-C), 55.33 (OCH3), 70.44 (CH2), 111.05, 118.28, 120.94, 123.17, 123.68, 128.32, 130.74, 130.95, 141.09, 152.23 (Ar & thio­phene-C), 155.42 (C=N), 177.74 (C=S).

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. The C-bound H atoms were positioned geometrically and treated as riding atoms: C—H 0.95–0.97 Å with Uiso(H) = 1.5Ueq(C-meth­yl) and 1.2Ueq(C) for other H atoms. The thienyl ring is disordered over two positions and in the final refinement cycles, the occupancy of atoms S2A and C16A, and S2B and C16B, were each fixed at 0.5.

Table 2
Experimental details

Crystal data
Chemical formula C18H20N4O2S2
Mr 388.5
Crystal system, space group Monoclinic, P21/c
Temperature (K) 100
a, b, c (Å) 15.2925 (2), 10.0745 (1), 11.9726 (1)
β (°) 93.413 (1)
V (Å3) 1841.28 (3)
Z 4
Radiation type Cu Kα
μ (mm−1) 2.80
Crystal size (mm) 0.70 × 0.51 × 0.41
 
Data collection
Diffractometer Agilent Xcalibur Ruby Gemini
Absorption correction Multi-scan (CrysAlis PRO; Agilent, 2014[Agilent (2014). CrysAlis PRO. Agilent Technologies, Yarnton, England.])
Tmin, Tmax 0.225, 0.315
No. of measured, independent and observed [I > 2σ(I)] reflections 13494, 3545, 3401
Rint 0.026
(sin θ/λ)max (Å−1) 0.612
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.045, 0.113, 1.04
No. of reflections 3494
No. of parameters 230
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.95, −0.65
Computer programs: CrysAlis CCD and CrysAlis RED (Oxford Diffraction, 2006[Oxford Diffraction (2006). CrysAlis CCD and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, England.]), SHELXS97 and SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), ORTEP-3 for Windows and WinGX (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]), Mercury (Macrae et al., 2008[Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466-470.]) and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Supporting information

CCDC reference: 1447823

Crystal structure: contains datablocks global, I. DOI: 10.1107/S2056989016000992/su5269sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S2056989016000992/su5269Isup2.hkl

Supporting information file. DOI: 10.1107/S2056989016000992/su5269Isup3.cml

checkCIF report


Chemical context top

1,3,4-Oxa­diazole derivatives are structural motifs of particular value in material sciences (Zhang et al., 2011) and agrochemistry (Shi et al., 2001; Milinkevich et al., 2009; Li et al., 2014). In addition, they occupy a unique situation in the field of medicinal chemistry as pharmacophores possessing diverse pharmacological activities including anti­bacterial (Ogata et al., 1971; Rane et al., 2012; Al-Omar, 2010), anti­cancer (Pinna et al., 2009; Gamal El-Din et al., 2015; Zhang et al., 2014; Du et al., 2013), anti­viral (Summa et al., 2008; Wu et al., 2015; El-Emam et al., 2004), anti­hypertensive (Vardan et al., 1983; Schlecker & Thieme, 1988), anti-inflammatory (Bansal et al., 2014; Kadi et al., 2007) and anti-oxidant (Ma et al., 2013) activities. In continuation to our previous studies on 1,3,4-oxa­diazo­les (El-Emam et al., 2012), we report herein on the synthesis and crystal structure of the title compound.

Structural commentary top

The title compound, Fig. 1, is composed of a methyl­(thio­phen-2-yl)-1,3,4-oxa­diazole-2(3H)-thione moiety linked to a 2-meth­oxy­phenyl unit via a bridging piperazine ring. The molecule is V-shaped with the mean plane of the piperazine ring, that has a chair conformation, making dihedral angles of 51.2 (1) and 77.8 (1)° with the 2-meth­oxy­phenyl ring and the oxa­diazole ring, respectively. The thio­phene ring mean plane lies almost in the plane of the oxa­diazole ring, with a dihedral angle of 4.35 (9)°. The thio­phene ring has an approximate 180 ° rotational disorder about the bridging C14—C15 bond.

Supra­molecular features top

In the crystal, molecules are linked by weak C—H···S hydrogen bonds and C—H···π inter­actions, forming layers in the bc plane (Table 1 and Fig. 2). The layers are linked via C—H···O hydrogen bonds and slipped parallel π–π inter­actions [Cg3··· Cg1i = 3.6729 (10) Å, inter-planar distance = 3.4757 (7) Å, slippage = 0.967 Å; Cg1 and Cg3 are the centroids of the S2A/C15/C16A/C17/C18 and O1/ N3/N4/C13/C14 rings, respectively; symmetry code (i): −x + 2, −y + 1, −z + 2], forming a three-dimensional structure (Table 1 and Fig. 2).

Database survey top

\ A search of the Cambridge Structural Database (Version 5.37, last update November 2015; Groom & Allen, 2014) for the 3-methyl-5-(thio­phen-2-yl)-1,3,4-oxa­diazole-2(3H)-thione moiety of the title compound gave three hits. Two of these compounds also contain a substituted piperazine ring, namely 3-[(4-phenyl­piperazin-1-yl)methyl]-5-(2-thienyl)-1,3,4-oxa­diazole-\ 2(3H)-thione (IDOBUA; El-Emam et al., 2013) and 3-[(4-benzyl­piperazin-1-yl)methyl]-5-(thio­phen-2-yl)-2,3-di­hydro-1,3,4-\ oxa­diazole-2-thione (VUBYUO; Al-Omary et al., 2015). In both of these molecules, the conformation is very similar to that of the title compound.

Synthesis and crystallization top

To a solution of 5-(thio­phen-2-yl)-1,3,4-oxa­diazole-2-thiol (920 mg, 5 mmol), in ethanol (15 ml), 1-(2-meth­oxy­phenyl)­piperazine (960 mg, 5 mmol) and 37% formaldehyde solution (1.0 ml) were added and the mixture was stirred at room temperature for 3 h and then allowed to stand overnight at room temperature. The precipitated crude product was filtered, washed with cold ethanol, dried, and crystallized from ethanol to yield the title compound as pale-yellow prismatic crystals(yield 1.67 g, 86%; m.p. 419–421 K). Single crystals suitable for X-ray analysis were obtained by slow evaporation of a CHCl3:EtOH solution (1:1; 15 ml) at room temperature. 1H NMR (CDCl3, 500.13 MHz): δ 3.10 (s, 8H, piperazine-H), 3.85 (s, 3H, OCH3), 5.15 (s, 2H, CH2), 6.85–6.87 (m, 1H, Ar—H), 6.92–6.95 (m, 2H, Ar—H), 7.01–7.03 (m, 1H, Ar—H), 7.18 (t, 1H, thio­phene-H, J = 4.5 Hz), 7.59 (d, 1H, thio­phene-H, J = 4.5 Hz), 7.75 (d, 1H, thio­phene-H, J = 4.5 Hz). 13C NMR (CDCl3, 125.76 MHz): δ 50.43, 50.64 (piperazine-C), 55.33 (OCH3), 70.44 (CH2), 111.05, 118.28, 120.94, 123.17, 123.68, 128.32, 130.74, 130.95, 141.09, 152.23 (Ar & thio­phene-C), 155.42 (C═N), 177.74 (C═S).

Refinement top

Crystal data, data collection and structure refinement details are summarized in Table 2. The C-bound H atoms were positioned geometrically and treated as riding atoms: C—H 0.95–0.97 Å with Uiso(H) = 1.5Ueq(C-methyl) and 1.2Ueq(C) for other H atoms. The thienyl ring is disordered over two positions and in the final refinement cycles, the occupancy of atoms S2A and C16A, and S2B and C16B, were each fixed at 0.5.

Structure description top

1,3,4-Oxa­diazole derivatives are structural motifs of particular value in material sciences (Zhang et al., 2011) and agrochemistry (Shi et al., 2001; Milinkevich et al., 2009; Li et al., 2014). In addition, they occupy a unique situation in the field of medicinal chemistry as pharmacophores possessing diverse pharmacological activities including anti­bacterial (Ogata et al., 1971; Rane et al., 2012; Al-Omar, 2010), anti­cancer (Pinna et al., 2009; Gamal El-Din et al., 2015; Zhang et al., 2014; Du et al., 2013), anti­viral (Summa et al., 2008; Wu et al., 2015; El-Emam et al., 2004), anti­hypertensive (Vardan et al., 1983; Schlecker & Thieme, 1988), anti-inflammatory (Bansal et al., 2014; Kadi et al., 2007) and anti-oxidant (Ma et al., 2013) activities. In continuation to our previous studies on 1,3,4-oxa­diazo­les (El-Emam et al., 2012), we report herein on the synthesis and crystal structure of the title compound.

The title compound, Fig. 1, is composed of a methyl­(thio­phen-2-yl)-1,3,4-oxa­diazole-2(3H)-thione moiety linked to a 2-meth­oxy­phenyl unit via a bridging piperazine ring. The molecule is V-shaped with the mean plane of the piperazine ring, that has a chair conformation, making dihedral angles of 51.2 (1) and 77.8 (1)° with the 2-meth­oxy­phenyl ring and the oxa­diazole ring, respectively. The thio­phene ring mean plane lies almost in the plane of the oxa­diazole ring, with a dihedral angle of 4.35 (9)°. The thio­phene ring has an approximate 180 ° rotational disorder about the bridging C14—C15 bond.

In the crystal, molecules are linked by weak C—H···S hydrogen bonds and C—H···π inter­actions, forming layers in the bc plane (Table 1 and Fig. 2). The layers are linked via C—H···O hydrogen bonds and slipped parallel π–π inter­actions [Cg3··· Cg1i = 3.6729 (10) Å, inter-planar distance = 3.4757 (7) Å, slippage = 0.967 Å; Cg1 and Cg3 are the centroids of the S2A/C15/C16A/C17/C18 and O1/ N3/N4/C13/C14 rings, respectively; symmetry code (i): −x + 2, −y + 1, −z + 2], forming a three-dimensional structure (Table 1 and Fig. 2).

\ A search of the Cambridge Structural Database (Version 5.37, last update November 2015; Groom & Allen, 2014) for the 3-methyl-5-(thio­phen-2-yl)-1,3,4-oxa­diazole-2(3H)-thione moiety of the title compound gave three hits. Two of these compounds also contain a substituted piperazine ring, namely 3-[(4-phenyl­piperazin-1-yl)methyl]-5-(2-thienyl)-1,3,4-oxa­diazole-\ 2(3H)-thione (IDOBUA; El-Emam et al., 2013) and 3-[(4-benzyl­piperazin-1-yl)methyl]-5-(thio­phen-2-yl)-2,3-di­hydro-1,3,4-\ oxa­diazole-2-thione (VUBYUO; Al-Omary et al., 2015). In both of these molecules, the conformation is very similar to that of the title compound.

Synthesis and crystallization top

To a solution of 5-(thio­phen-2-yl)-1,3,4-oxa­diazole-2-thiol (920 mg, 5 mmol), in ethanol (15 ml), 1-(2-meth­oxy­phenyl)­piperazine (960 mg, 5 mmol) and 37% formaldehyde solution (1.0 ml) were added and the mixture was stirred at room temperature for 3 h and then allowed to stand overnight at room temperature. The precipitated crude product was filtered, washed with cold ethanol, dried, and crystallized from ethanol to yield the title compound as pale-yellow prismatic crystals(yield 1.67 g, 86%; m.p. 419–421 K). Single crystals suitable for X-ray analysis were obtained by slow evaporation of a CHCl3:EtOH solution (1:1; 15 ml) at room temperature. 1H NMR (CDCl3, 500.13 MHz): δ 3.10 (s, 8H, piperazine-H), 3.85 (s, 3H, OCH3), 5.15 (s, 2H, CH2), 6.85–6.87 (m, 1H, Ar—H), 6.92–6.95 (m, 2H, Ar—H), 7.01–7.03 (m, 1H, Ar—H), 7.18 (t, 1H, thio­phene-H, J = 4.5 Hz), 7.59 (d, 1H, thio­phene-H, J = 4.5 Hz), 7.75 (d, 1H, thio­phene-H, J = 4.5 Hz). 13C NMR (CDCl3, 125.76 MHz): δ 50.43, 50.64 (piperazine-C), 55.33 (OCH3), 70.44 (CH2), 111.05, 118.28, 120.94, 123.17, 123.68, 128.32, 130.74, 130.95, 141.09, 152.23 (Ar & thio­phene-C), 155.42 (C═N), 177.74 (C═S).

Refinement details top

Crystal data, data collection and structure refinement details are summarized in Table 2. The C-bound H atoms were positioned geometrically and treated as riding atoms: C—H 0.95–0.97 Å with Uiso(H) = 1.5Ueq(C-methyl) and 1.2Ueq(C) for other H atoms. The thienyl ring is disordered over two positions and in the final refinement cycles, the occupancy of atoms S2A and C16A, and S2B and C16B, were each fixed at 0.5.

Computing details top

Data collection: CrysAlis CCD (Oxford Diffraction, 2006); cell refinement: CrysAlis CCD (Oxford Diffraction, 2006); data reduction: CrysAlis RED (Oxford Diffraction, 2006); 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) and Mercury (Macrae et al., 2008); software used to prepare material for publication: WinGX (Farrugia, 2012) and publCIF (Westrip, 2010).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound, showing the atom-labelling scheme and displacement ellipsoids at the 50% probability level.
[Figure 2] Fig. 2. Crystal packing of the title compound, viewed along the b axis, showing the C—H···S and C—H···O hydrogen bonds (Table 1) as dashed lines. Only H atoms involved in intermolecular interactions have been included.
3-{[4-(2-Methoxyphenyl)piperazin-1-yl]methyl}-5-(thiophen-2-yl)-1,3,4-oxadiazole-2(3H)-thione top
Crystal data top
C18H20N4O2S2F(000) = 816
Mr = 388.5Dx = 1.401 Mg m−3
Monoclinic, P21/cCu Kα radiation, λ = 1.54184 Å
Hall symbol: -P 2ybcCell parameters from 11296 reflections
a = 15.2925 (2) Åθ = 3.7–70.5°
b = 10.0745 (1) ŵ = 2.80 mm−1
c = 11.9726 (1) ÅT = 100 K
β = 93.413 (1)°Prism, colourless
V = 1841.28 (3) Å30.70 × 0.51 × 0.41 mm
Z = 4
Data collection top
Agilent Xcalibur Ruby Gemini
diffractometer		3545 independent reflections
Radiation source: Enhance (Cu) X-ray Source3401 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.026
Detector resolution: 10.2673 pixels mm-1θmax = 70.7°, θmin = 5.3°
ω scansh = −18→17
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2014)		k = −8→12
Tmin = 0.225, Tmax = 0.315l = −14→14
13494 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.045Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.113H-atom parameters constrained
S = 1.04 w = 1/[σ2(Fo2) + (0.0574P)2 + 2.048P]
where P = (Fo2 + 2Fc2)/3
3494 reflections(Δ/σ)max < 0.001
230 parametersΔρmax = 0.95 e Å−3
0 restraintsΔρmin = −0.65 e Å−3
0 constraints
Crystal data top
C18H20N4O2S2V = 1841.28 (3) Å3
Mr = 388.5Z = 4
Monoclinic, P21/cCu Kα radiation
a = 15.2925 (2) ŵ = 2.80 mm−1
b = 10.0745 (1) ÅT = 100 K
c = 11.9726 (1) Å0.70 × 0.51 × 0.41 mm
β = 93.413 (1)°
Data collection top
Agilent Xcalibur Ruby Gemini
diffractometer		3545 independent reflections
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2014)		3401 reflections with I > 2σ(I)
Tmin = 0.225, Tmax = 0.315Rint = 0.026
13494 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0450 restraints
wR(F2) = 0.113H-atom parameters constrained
S = 1.04Δρmax = 0.95 e Å−3
3494 reflectionsΔρmin = −0.65 e Å−3
230 parameters
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
S10.89998 (3)0.09896 (5)0.99378 (4)0.02414 (15)
S2A0.87403 (4)0.74266 (6)1.04820 (5)0.02497 (16)0.7913 (14)
C16A0.94021 (8)0.57554 (13)1.21094 (10)0.02497 (16)0.7913 (14)
H16A0.95980.5011.25080.03*0.7913 (14)
S2B0.94021 (8)0.57554 (13)1.21094 (10)0.02497 (16)0.2087 (14)
C16B0.87403 (4)0.74266 (6)1.04820 (5)0.02497 (16)0.2087 (14)
H16B0.85020.7790.98170.03*0.2087 (14)
O10.90631 (8)0.35048 (13)1.06190 (11)0.0189 (3)
O20.43793 (9)0.38449 (17)0.90935 (12)0.0312 (4)
N30.85646 (10)0.33316 (16)0.89001 (13)0.0192 (3)
N10.55319 (10)0.37224 (16)0.74811 (13)0.0198 (3)
N40.85770 (10)0.46847 (16)0.91387 (13)0.0204 (3)
N20.73225 (10)0.29806 (17)0.75238 (13)0.0210 (3)
C10.46191 (12)0.37565 (18)0.71654 (16)0.0202 (4)
C150.90176 (11)0.58606 (19)1.08927 (15)0.0183 (4)
C140.88737 (11)0.47285 (19)1.01696 (15)0.0180 (4)
C130.88567 (12)0.26006 (19)0.97769 (15)0.0187 (4)
C60.40227 (13)0.3813 (2)0.80197 (17)0.0229 (4)
C90.67626 (13)0.2461 (2)0.83683 (17)0.0237 (4)
H9A0.68060.30250.90260.028*
H9B0.69550.15770.85890.028*
C110.61058 (12)0.4202 (2)0.66366 (16)0.0231 (4)
H11A0.59080.50660.63680.028*
H11B0.60880.35960.60070.028*
C40.28120 (13)0.3853 (2)0.66375 (19)0.0278 (5)
H40.22110.38750.64630.033*
C30.33874 (14)0.3826 (2)0.57913 (18)0.0284 (5)
H30.31770.38440.50460.034*
C20.42871 (13)0.3770 (2)0.60627 (17)0.0249 (4)
H20.46720.37410.54910.03*
C100.70379 (12)0.4304 (2)0.71497 (16)0.0228 (4)
H10A0.74240.46380.660.027*
H10B0.70580.49120.77790.027*
C80.58162 (13)0.2411 (2)0.78978 (18)0.0240 (4)
H8A0.57630.1770.72920.029*
H8B0.54410.21250.84780.029*
C50.31283 (13)0.3849 (2)0.77469 (18)0.0275 (5)
H50.27380.38690.83130.033*
C120.82390 (12)0.2821 (2)0.77866 (15)0.0224 (4)
H12A0.85550.32680.72170.027*
H12B0.83790.18830.77490.027*
C170.93757 (13)0.7167 (2)1.24746 (17)0.0268 (4)
H170.95710.74211.31930.032*
C70.38537 (15)0.4430 (3)0.99152 (19)0.0342 (5)
H7A0.41670.44031.06340.051*
H7B0.33160.39430.99470.051*
H7C0.37260.53350.97150.051*
C180.90558 (13)0.8060 (2)1.1716 (2)0.0297 (5)
H180.90160.89611.18740.036*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0282 (3)0.0197 (3)0.0246 (3)0.00178 (18)0.00181 (19)0.00051 (18)
S2A0.0229 (3)0.0257 (3)0.0265 (3)−0.0011 (2)0.0022 (2)−0.0008 (2)
C16A0.0229 (3)0.0257 (3)0.0265 (3)−0.0011 (2)0.0022 (2)−0.0008 (2)
S2B0.0229 (3)0.0257 (3)0.0265 (3)−0.0011 (2)0.0022 (2)−0.0008 (2)
C16B0.0229 (3)0.0257 (3)0.0265 (3)−0.0011 (2)0.0022 (2)−0.0008 (2)
O10.0189 (6)0.0199 (6)0.0177 (6)0.0015 (5)0.0001 (5)0.0003 (5)
O20.0213 (7)0.0510 (10)0.0218 (7)−0.0010 (6)0.0057 (6)−0.0044 (6)
N30.0175 (7)0.0216 (8)0.0184 (8)0.0028 (6)0.0006 (6)−0.0007 (6)
N10.0161 (8)0.0234 (8)0.0201 (8)0.0005 (6)0.0037 (6)0.0027 (6)
N40.0196 (8)0.0219 (8)0.0197 (8)0.0030 (6)0.0022 (6)0.0002 (6)
N20.0170 (8)0.0260 (8)0.0201 (8)0.0035 (6)0.0011 (6)0.0002 (7)
C10.0175 (9)0.0190 (9)0.0244 (10)−0.0012 (7)0.0030 (7)0.0003 (7)
C150.0141 (8)0.0219 (9)0.0191 (9)0.0009 (7)0.0019 (7)0.0014 (7)
C140.0128 (8)0.0209 (9)0.0204 (9)0.0022 (7)0.0029 (7)0.0023 (7)
C130.0143 (8)0.0241 (10)0.0182 (9)0.0006 (7)0.0031 (7)−0.0016 (7)
C60.0216 (10)0.0233 (10)0.0239 (10)−0.0022 (8)0.0034 (8)0.0000 (8)
C90.0218 (10)0.0248 (10)0.0245 (10)0.0031 (8)0.0021 (8)0.0047 (8)
C110.0177 (9)0.0309 (11)0.0211 (9)0.0008 (8)0.0031 (7)0.0060 (8)
C40.0163 (9)0.0309 (11)0.0360 (11)−0.0025 (8)0.0000 (8)0.0014 (9)
C30.0228 (10)0.0351 (12)0.0267 (10)−0.0024 (8)−0.0019 (8)0.0032 (9)
C20.0197 (9)0.0309 (11)0.0246 (10)−0.0008 (8)0.0042 (8)0.0010 (8)
C100.0177 (9)0.0284 (10)0.0224 (9)−0.0002 (8)0.0024 (7)0.0055 (8)
C80.0203 (9)0.0228 (10)0.0290 (10)−0.0003 (7)0.0030 (8)0.0035 (8)
C50.0197 (10)0.0331 (11)0.0307 (11)−0.0032 (8)0.0087 (8)−0.0001 (9)
C120.0204 (9)0.0295 (10)0.0174 (9)0.0047 (8)0.0017 (7)−0.0042 (8)
C170.0173 (9)0.0420 (12)0.0211 (9)−0.0069 (8)0.0027 (7)−0.0057 (9)
C70.0326 (11)0.0442 (13)0.0272 (11)−0.0067 (10)0.0117 (9)−0.0083 (10)
C180.0240 (10)0.0230 (10)0.0432 (12)−0.0017 (8)0.0102 (9)−0.0017 (9)
Geometric parameters (Å, º) top
S1—C131.647 (2)C9—H9A0.97
S2A—C181.655 (2)C9—H9B0.97
S2A—C151.6988 (19)C11—C101.522 (3)
C16A—C171.489 (3)C11—H11A0.97
C16A—C151.542 (2)C11—H11B0.97
C16A—H16A0.93C4—C31.381 (3)
O1—C141.369 (2)C4—C51.386 (3)
O1—C131.381 (2)C4—H40.93
O2—C61.367 (3)C3—C21.396 (3)
O2—C71.434 (3)C3—H30.93
N3—C131.337 (2)C2—H20.93
N3—N41.393 (2)C10—H10A0.97
N3—C121.487 (2)C10—H10B0.97
N1—C11.425 (2)C8—H8A0.97
N1—C111.460 (2)C8—H8B0.97
N1—C81.469 (2)C5—H50.93
N4—C141.290 (2)C12—H12A0.97
N2—C121.427 (2)C12—H12B0.97
N2—C91.460 (2)C17—C181.349 (3)
N2—C101.464 (3)C17—H170.93
C1—C21.386 (3)C7—H7A0.96
C1—C61.412 (3)C7—H7B0.96
C15—C141.441 (3)C7—H7C0.96
C6—C51.388 (3)C18—H180.93
C9—C81.522 (3)
C18—S2A—C1592.58 (10)C3—C4—C5120.10 (19)
C17—C16A—C15101.32 (13)C3—C4—H4120
C17—C16A—H16A129.3C5—C4—H4120
C15—C16A—H16A129.3C4—C3—C2119.49 (19)
C14—O1—C13105.85 (14)C4—C3—H3120.3
C6—O2—C7116.52 (17)C2—C3—H3120.3
C13—N3—N4112.23 (15)C1—C2—C3121.48 (19)
C13—N3—C12126.27 (17)C1—C2—H2119.3
N4—N3—C12121.49 (15)C3—C2—H2119.3
C1—N1—C11115.34 (15)N2—C10—C11108.46 (16)
C1—N1—C8112.16 (15)N2—C10—H10A110
C11—N1—C8110.80 (15)C11—C10—H10A110
C14—N4—N3103.26 (15)N2—C10—H10B110
C12—N2—C9114.55 (15)C11—C10—H10B110
C12—N2—C10116.12 (16)H10A—C10—H10B108.4
C9—N2—C10111.25 (15)N1—C8—C9110.57 (16)
C2—C1—C6118.29 (18)N1—C8—H8A109.5
C2—C1—N1123.40 (17)C9—C8—H8A109.5
C6—C1—N1118.28 (17)N1—C8—H8B109.5
C14—C15—C16A123.32 (15)C9—C8—H8B109.5
C14—C15—S2A122.32 (14)H8A—C8—H8B108.1
C16A—C15—S2A114.33 (12)C4—C5—C6120.56 (19)
N4—C14—O1113.53 (16)C4—C5—H5119.7
N4—C14—C15129.37 (18)C6—C5—H5119.7
O1—C14—C15117.09 (16)N2—C12—N3115.51 (15)
N3—C13—O1105.12 (16)N2—C12—H12A108.4
N3—C13—S1132.09 (15)N3—C12—H12A108.4
O1—C13—S1122.77 (14)N2—C12—H12B108.4
O2—C6—C5123.60 (18)N3—C12—H12B108.4
O2—C6—C1116.35 (17)H12A—C12—H12B107.5
C5—C6—C1120.05 (19)C18—C17—C16A117.01 (18)
N2—C9—C8109.84 (16)C18—C17—H17121.5
N2—C9—H9A109.7C16A—C17—H17121.5
C8—C9—H9A109.7O2—C7—H7A109.5
N2—C9—H9B109.7O2—C7—H7B109.5
C8—C9—H9B109.7H7A—C7—H7B109.5
H9A—C9—H9B108.2O2—C7—H7C109.5
N1—C11—C10109.26 (15)H7A—C7—H7C109.5
N1—C11—H11A109.8H7B—C7—H7C109.5
C10—C11—H11A109.8C17—C18—S2A114.76 (17)
N1—C11—H11B109.8C17—C18—H18122.6
C10—C11—H11B109.8S2A—C18—H18122.6
H11A—C11—H11B108.3
C13—N3—N4—C14−0.5 (2)N1—C1—C6—O20.7 (3)
C12—N3—N4—C14178.38 (15)C2—C1—C6—C51.5 (3)
C11—N1—C1—C222.5 (3)N1—C1—C6—C5179.97 (18)
C8—N1—C1—C2−105.7 (2)C12—N2—C9—C8−167.82 (16)
C11—N1—C1—C6−155.90 (18)C10—N2—C9—C858.0 (2)
C8—N1—C1—C676.0 (2)C1—N1—C11—C10171.49 (16)
C17—C16A—C15—C14−177.76 (16)C8—N1—C11—C10−59.7 (2)
C17—C16A—C15—S2A0.16 (15)C5—C4—C3—C21.1 (3)
C18—S2A—C15—C14177.79 (16)C6—C1—C2—C3−0.5 (3)
C18—S2A—C15—C16A−0.16 (13)N1—C1—C2—C3−178.91 (19)
N3—N4—C14—O10.53 (19)C4—C3—C2—C1−0.8 (3)
N3—N4—C14—C15−178.64 (17)C12—N2—C10—C11165.92 (15)
C13—O1—C14—N4−0.4 (2)C9—N2—C10—C11−60.7 (2)
C13—O1—C14—C15178.90 (15)N1—C11—C10—N260.7 (2)
C16A—C15—C14—N4−178.37 (16)C1—N1—C8—C9−172.53 (16)
S2A—C15—C14—N43.9 (3)C11—N1—C8—C957.0 (2)
C16A—C15—C14—O12.5 (2)N2—C9—C8—N1−55.2 (2)
S2A—C15—C14—O1−175.28 (13)C3—C4—C5—C6−0.2 (3)
N4—N3—C13—O10.29 (19)O2—C6—C5—C4178.1 (2)
C12—N3—C13—O1−178.53 (15)C1—C6—C5—C4−1.2 (3)
N4—N3—C13—S1−178.25 (15)C9—N2—C12—N3−52.8 (2)
C12—N3—C13—S12.9 (3)C10—N2—C12—N379.1 (2)
C14—O1—C13—N30.03 (18)C13—N3—C12—N2110.8 (2)
C14—O1—C13—S1178.74 (13)N4—N3—C12—N2−67.9 (2)
C7—O2—C6—C5−24.0 (3)C15—C16A—C17—C18−0.1 (2)
C7—O2—C6—C1155.31 (19)C16A—C17—C18—S2A0.0 (2)
C2—C1—C6—O2−177.78 (18)C15—S2A—C18—C170.11 (17)
Hydrogen-bond geometry (Å, º) top
Cg1 is the centroid of the S2A/C15/C16A/C17/C18 ring.
D—H···AD—HH···AD···AD—H···A
C12—H12A···S1i0.972.953.860 (2)157
C17—H17···O1ii0.932.693.475 (2)143
C5—H5···Cg1iii0.932.953.660 (2)135
Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) −x+2, y+1/2, −z+5/2; (iii) −x+1, −y+1, −z+2.
Hydrogen-bond geometry (Å, º) top
Cg1 is the centroid of the S2A/C15/C16A/C17/C18 ring.
D—H···AD—HH···AD···AD—H···A
C12—H12A···S1i0.972.953.860 (2)157
C17—H17···O1ii0.932.693.475 (2)143
C5—H5···Cg1iii0.932.953.660 (2)135
Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) −x+2, y+1/2, −z+5/2; (iii) −x+1, −y+1, −z+2.

Experimental details

Crystal data
Chemical formulaC18H20N4O2S2
Mr388.5
Crystal system, space groupMonoclinic, P21/c
Temperature (K)100
a, b, c (Å)15.2925 (2), 10.0745 (1), 11.9726 (1)
β (°) 93.413 (1)
V (Å3)1841.28 (3)
Z4
Radiation typeCu Kα
µ (mm−1)2.80
Crystal size (mm)0.70 × 0.51 × 0.41
Data collection
DiffractometerAgilent Xcalibur Ruby Gemini
Absorption correctionMulti-scan
(CrysAlis PRO; Agilent, 2014)
Tmin, Tmax0.225, 0.315
No. of measured, independent and
observed [I > 2σ(I)] reflections		13494, 3545, 3401
Rint0.026
(sin θ/λ)max (Å−1)0.612
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.045, 0.113, 1.04
No. of reflections3494
No. of parameters230
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å−3)0.95, −0.65

Computer programs: CrysAlis CCD (Oxford Diffraction, 2006), CrysAlis RED (Oxford Diffraction, 2006), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 2012) and Mercury (Macrae et al., 2008), WinGX (Farrugia, 2012) and publCIF (Westrip, 2010).

 

Footnotes

‡Additional correspondence author, e-mail: elemam5@hotmail.com.

Acknowledgements

The authors extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding this study through the Research Group Project No. PRG-1436–23. We also acknowledge financial support from the Spanish Ministerio de Economía y Competitividad (MINECO-13-MAT2013–40950-R, FPI grant BES-2011–046948 to MSMA).

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ISSN: 2056-9890
Volume 72| Part 2| February 2016| Pages 269-272
doi:10.1107/S2056989016000992
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