2-(5-Fluoro-2,3-dioxoindolin-1-yl)ethyl 4-methyl­piperazine-1-carbodithio­ate

Yao Wang; Hui-Hui Lin; Sheng-Li Cao

doi:10.1107/S1600536811052494

. 2011 Dec 10;68(Pt 1):o94–o95. doi: 10.1107/S1600536811052494

2-(5-Fluoro-2,3-dioxoindolin-1-yl)ethyl 4-methylpiperazine-1-carbodithioate

Yao Wang ^a, Hui-Hui Lin ^a, Sheng-Li Cao ^a,^*

PMCID: PMC3254445 PMID: 22259593

Abstract

In the title compound, C₁₆H₁₈FN₃O₂S₂, the methylpiperazine ring adopts a chair conformation, while the (2,3-dioxoindolin-1-yl)ethyl unit is linked to one of the N atoms of the piperazine ring via the carbodithioate group. In the crystal, each molecule is linked to its neighbors within the ( Inline graphic 03) plane through weak C—H(methylene)⋯O, C—H(aryl)⋯O and C—H(methylene)⋯S interactions. Perpendicular to this plane molecules are connected through intermolecular short N⋯π(pyrrole ring) contacts [N⋯C centroid = 3.232 (2) Å], another set of C—H(methylene)⋯O interactions and through short contacts between carbodithioate S atoms and the pyrrole rings [C⋯centroid = 3.695 (3), S⋯centroid = 3.403 (2) Å].

Related literature

For background to indoline-2,3-dione and its derivatives, see: Bhattacharya & Chakrabarti (1998 ▶); Sridhar & Ramesh (2001 ▶); Medvedev et al. (1996 ▶) and to dithiocarbamates, see: Ozkirimli et al. (2005 ▶); Cao et al. (2005 ▶); Gaspari et al. (2006 ▶). For analogues of 5-fluoroindoline-2,3-dione, see: Wang et al. (2010 ▶). For N⋯π contacts, see: Black et al. (2007 ▶). For van der Waals radii, see Bondi (1964 ▶). For the thickness of phenyl rings, see: Malone et al. (1997 ▶). For C=O⋯π (pyridyl) contacts, see: Wan et al. (2008 ▶)

Experimental

Crystal data

C₁₆H₁₈FN₃O₂S₂
M _r = 367.45
Monoclinic,
a = 10.0258 (4) Å
b = 15.9925 (6) Å
c = 11.0016 (5) Å
β = 106.656 (3)°
V = 1689.96 (12) Å³
Z = 4
Mo Kα radiation
μ = 0.34 mm⁻¹
T = 296 K
0.30 × 0.30 × 0.20 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker 2007 ▶) T _min = 0.658, T _max = 0.746
18809 measured reflections
3861 independent reflections
3058 reflections with I > 2σ(I)
R _int = 0.031

Refinement

R[F ² > 2σ(F ²)] = 0.035
wR(F ²) = 0.100
S = 1.04
3861 reflections
217 parameters
H-atom parameters constrained
Δρ_max = 0.22 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: APEX2 and SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536811052494/zl2432sup1.cif

e-68-00o94-sup1.cif^{(25.4KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811052494/zl2432Isup2.hkl

e-68-00o94-Isup2.hkl^{(189.3KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811052494/zl2432Isup3.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
C13—H13B⋯O2ⁱ	0.97	2.50	3.225 (2)	131
C12—H12A⋯O2ⁱⁱ	0.97	2.61	3.385 (2)	137
C15—H15B⋯O2ⁱⁱ	0.97	2.62	3.383 (2)	136
C1—H1A⋯O1ⁱⁱⁱ	0.93	2.70	3.282 (3)	121
C2—H2A⋯O1ⁱⁱⁱ	0.93	2.67	3.275 (2)	124
C12—H12B⋯S2ⁱ	0.97	2.97	3.866 (3)	155

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

Acknowledgments

The authors are grateful to the National Natural Science Foundation of China (project No. 20972099) and the Beijing Municipal Commission of Education for financial support.

supplementary crystallographic information

Comment

Indoline-2,3-dione and its derivatives are well known for their broad spectrum biological and pharmacological properties including anticonvulsant (Bhattacharya & Chakrabarti, 1998), anti-inflammatory (Sridhar et al., 2001) and anxiogenic (Medvedev et al., 1996) activities. On the other hand, dithiocarbamates also exhibit a large range of biological activities such as fungicidal (Ozkirimli et al., 2005) and antitumor activities (Cao et al., 2005; Gaspari et al., 2006). In an attempt to obtain compounds that might also exhibit antitumor properties, but possibly with increased potency and selectivity, we designed and synthesized the title compoud (C₁₆H₁₈N₃O₂FS₂), which consists of an indole core with a dithiocarbamate side chain (Scheme 1). In the present context, we report the crystal structure of the new compound.

In the crystalline structure of the title compound, the 1-methylpiperazine ring adopts a chair conformation, while the indoline-2,3-dione ethyl moiety is linked to one of the N atoms of the piperazine ring via the carbodithioate group, with the ethyl group in a trans-conformation (N1—C9—C10—S2 torsion angle of 175.74 (11)°, Fig. 1). This trans-conformation differentiates the title compound from the related compound 2-(2,3-dioxoindolin-1-yl)ethyl-4-(4-nitrophenyl)piperazine-1-carbodithioate reported by us recently (Wang et al., 2010), which was found to have a gauge-conformation with an N4(pyrrole)—C19—C20—S2 torsion angle of 66.16 (15)°. Through weak C13—H13B(methylene)···O2ⁱ, C—H(aryl)···O1ⁱⁱ and C12—H12B(methylene)···S2ⁱⁱⁱ interactions each molecule is linked to its neighbors within the (-1 0 3) Miller plane (Table 1 and Fig. 2). Perpendicular to this plane molecules are connected through intermolecular short N···π (pyrrole ring) contacts, another set of C—H(methylene)···O interactions (Table 1) and through short contacts between carbodithioate sulfur atoms and the pyrrole rings (C11═S1···Cg1^iv, Table 2). A short contact is observed between the nitrogen atom N1 and the π-electron desnity of the pyrrole ring, with an N3···Cg^v (Cg = C5-C6-C7-N1-C8, (v) = -x+1.5, y+0.5, -z+1.5) distance equal to 3.232 (2) Å, which is shorter than the van der Waals distance (3.40 Å) on the basis of Pauling's value for the half thickness of phenyl rings (1.85 Å) (Malone et al.,1997) and the van der Waals radius of N (1.55 Å) (Bondi, 1964). It is comparable to the N(pyrazinyl)···centroid(pyrazinyl) distance of 3.05 Å in {[Ni(L)(NO₃)₂]}_∞ (L = bis(2-pyraylmethyl)sulfide) reported by Black et al. (2007). Regarding the C11═S1···π contact (Table 2), the C═S bond is almost parallel to the pyrrole ring with a C11═S1···Cg1(pyrrole) angle equal to 86.42 (2)°, a contact mode similar to that of the C═O···π (pyridyl) contact in Cu(L)₂(BF₄)₂ (L = 2,6-pyridinediylbis(3-pyridinyl)methanone) reported by Wan et al. (2008).

Experimental

A suspension of 1-methylpiperazine (2.4 mmol), carbon disulfide (0.72 mL, 12 mmol) and anhydrous potassium phosphate (0.51 g, 2.4 mmol) in N,N-dimethylformamide (15 mL) was stirred at room temperature for 30 minutes. Then, 1-(2-bromoethyl)-5-fluoroindoline-2,3-dione (2 mmol) was added and stirring was continued for 3.5 h. The reaction mixture was poured into water (100 mL) and the resulting precipitate was separated by filtration and further purified by column chromatography on silica gel with dichloromethane/methanol = 95:5 (v/v) as the eluent to give the title compound (R_f = 0.44, m.p. 472.2-473.2 K; yield 78%). After two weeks, the orange crystals of the title compound were deposited by slow evaporation from a solution of dichloromethane/N,N-dimethylformamide 1:1 (v/v) at room temperature.