4-Benzyl-N-methyl­piperazine-1-carbothio­amide

Amer M Alanazi; Ali A El-Emam; Nasser R El-Brollosy; Seik Weng Ng; Edward R T Tiekink

doi:10.1107/S1600536812005685

. 2012 Feb 17;68(Pt 3):o712–o713. doi: 10.1107/S1600536812005685

4-Benzyl-N-methylpiperazine-1-carbothioamide

Amer M Alanazi ^a,^‡, Ali A El-Emam ^a, Nasser R El-Brollosy ^a, Seik Weng Ng ^b,^§, Edward R T Tiekink ^b,^*

PMCID: PMC3295486 PMID: 22412597

Abstract

The asymmetric unit in the title thiourea derivative, C₁₃H₁₉N₃S, comprises three independent molecules (A, B and C). The thiourea groups are superimposable for the three molecules, but there are significant conformational differences. Molecules A and B are approximate mirror images of each other, and molecule C has an intermediate conformation. The dihedral angles between the thiourea groups and the phenyl rings are 52.10 (5), 63.29 (5) and 66.46 (6)° in molecules A, B and C, respectively. Each independent molecule self-associates into a supramolecular chain along [100] via N—H⋯S hydrogen bonds. Molecules of A and B assemble into layers four molecules thick in the ac plane via C—H⋯S and C—H⋯π interactions. Molecules of C self-assemble into layers in the ac plane via C—H⋯S interactions. The layers stack along the b axis with no specific interactions between them.

Related literature

For the various biological activities exhibited by 1,4-disubstituted piperazine derivatives, see: Kadi et al. (2010 ▶); Al Hussainy et al. (2011 ▶); Moussa et al. (2011 ▶); Kamiński et al. (2011 ▶); Sheng et al. (2011 ▶); Yang et al. (2011 ▶); Liu et al. (2011 ▶).

Experimental

Crystal data

C₁₃H₁₉N₃S
M _r = 249.37
Monoclinic,
a = 5.8472 (1) Å
b = 80.3936 (9) Å
c = 8.6219 (1) Å
β = 103.292 (1)°
V = 3944.39 (9) Å³
Z = 12
Cu Kα radiation
μ = 2.03 mm⁻¹
T = 100 K
0.40 × 0.30 × 0.20 mm

Data collection

Agilent SuperNova Dual diffractometer with an Atlas detector
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011 ▶) T _min = 0.497, T _max = 0.687
45632 measured reflections
7865 independent reflections
7864 reflections with I > 2σ(I)
R _int = 0.023

Refinement

R[F ² > 2σ(F ²)] = 0.032
wR(F ²) = 0.087
S = 1.03
7865 reflections
475 parameters
5 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.28 e Å⁻³
Absolute structure: Flack (1983 ▶), 3714 Friedel pairs
Flack parameter: 0.020 (8)

Data collection: CrysAlis PRO (Agilent, 2011 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: X-SEED (Barbour, 2001 ▶), DIAMOND (Brandenburg, 2006 ▶) and Qmol (Gans & Shalloway, 2001 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812005685/pk2388sup1.cif

e-68-0o712-sup1.cif^{(31.6KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812005685/pk2388Isup2.hkl

e-68-0o712-Isup2.hkl^{(384.8KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812005685/pk2388Isup3.cml

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

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

Cg1 is the centroid of the C21–C26 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯S1ⁱ	0.87 (1)	2.59 (2)	3.387 (2)	153 (2)
N4—H4⋯S2ⁱ	0.88 (1)	2.64 (2)	3.367 (2)	140 (2)
N7—H7⋯S3ⁱⁱ	0.87 (1)	2.65 (2)	3.397 (2)	144 (2)
C3—H3b⋯S1ⁱⁱⁱ	0.99	2.83	3.8213 (17)	175
C22—H22⋯S2^iv	0.95	2.87	3.7867 (17)	163
C29—H29b⋯S3^v	0.99	2.86	3.8007 (17)	160
C10—H10⋯Cg1^vi	0.95	2.64	3.5665 (18)	164

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

Acknowledgments

The financial support of the Deanship of Scientific Research and the Research Center of the College of Pharmacy, King Saud University, is greatly appreciated. We also thank the Ministry of Higher Education (Malaysia) for funding structural studies through the High-Impact Research scheme (UM.C/HIR/MOHE/SC/12).

supplementary crystallographic information

Comment

1,4-Disubstituted piperazine derivatives are known for their diverse biological activities such as a CNS stimulant (Al Hussainy et al., 2011; Moussa et al., 2011), anti-convulsant (Kamiński et al., 2011), anti-microbial (Sheng et al., 2011), anti-cancer (Yang et al. 2011) and histamine antagonist (Liu et al., 2011). In continuation of our interest in the chemical and pharmacological properties of 1,4-piperazine derivatives (Kadi et al., 2010), we synthesized the title compound, (I), as an intermediate for potential chemotherapeutic agents.

Three independent molecules comprise the asymmetric unit of (I), Fig. 1. There are significant differences in conformation between these as highlighted in Fig. 2. The independent molecules containing the S1 and S2 are approximately mirror images of each other and the conformation of the S3 containing molecule is intermediate between those of the others. The dihedral angles formed between the thiourea moiety and the phenyl rings are 52.10 (5), 63.29 (5) and 66.46 (6)°, respectively. Each piperazine ring has a chair conformation.

Each independent molecule self-associates into a supramolecular chain via N—H···S hydrogen bonds, Table 1. Chains are orientated along the a axis and an example is illustrated for the S1-containing molecule in Fig. 3. In the crystal packing, the S1- and S2-containing chains are connected into layers four molecules thick via C—H···S and C—H···π interactions. The S3-containing molecules are also connected into layers via C—H···S interactions. Globally, layers, which are formed in the ac plane, stack along the b axis, Fig. 4, with no specific interactions between them.

Experimental

Methyl isothiocyanate (3.66 g, 0.05 mol) was added to a solution of 1-benzylpiperazine (8.81 g, 0.05 mol) in ethanol (15 ml). The mixture was stirred for 5 min. at room temperature and allowed to stand for 1 h. The separated crude product was filtered, washed with cold ethanol, dried and crystallized from ethanol to yield 11.60 g (93%) of the title compound as colourless crystals. M.p.: 365–367 K.