N′-[(2Z)-3-Allyl-4-oxo-1,3-thia­zolidin-2-yl­idene]-5-fluoro-3-phenyl-1H-indole-2-carbohydrazide

Mehmet Akkurt; Selvi Karaca; Gökçe Cihan; Gültaze Çapan; Orhan Büyükgüngör

doi:10.1107/S1600536809012677

. 2009 Apr 8;65(Pt 5):o1009–o1010. doi: 10.1107/S1600536809012677

N′-[(2Z)-3-Allyl-4-oxo-1,3-thiazolidin-2-ylidene]-5-fluoro-3-phenyl-1H-indole-2-carbohydrazide

Mehmet Akkurt ^a,^*, Selvi Karaca ^a, Gökçe Cihan ^b, Gültaze Çapan ^b, Orhan Büyükgüngör ^c

PMCID: PMC2977697 PMID: 21583833

Abstract

In the title compound, C₂₁H₁₇FN₄O₂S, the planar indole fused-ring [maximum deviation 0.009 (1) Å] makes dihedral angles of 54.75 (9) and 14.90 (9)°, respectively, with the phenyl ring and the dihydrothiazolyl ring. The –CH2CH=CH₂ substituent is disordered over two positions in a 0.51 (1):0.49 (1) ratio. An intramolecular N—H⋯S hydrogen bond generates an S(5) ring motif. The two independent molecules are linked into a dimer by two N—H⋯O hydrogen bonds, forming an R ₂ ²(10) ring motif. The crystal structure features intermolecular C—H⋯π and π–π stacking [centroid–centroid distance = 3.679 (1) Å] interactions. C—H⋯O and C—H⋯F interactions are also present.

Related literature

For the bactericidal, fungicidal, antitubercular and anticancer properties of 4-thiazolidinone derivatives, see: Bonde & Gaikwad (2004 ▶); Güzel et al. (2006 ▶); Küçükgüzel et al. (2002 ▶); Kline et al. (2008 ▶); Ottanà et al. (2005 ▶); Ulusoy (2002 ▶); Zhou et al. (2008 ▶); Çapan et al. (1999 ▶).

Experimental

Crystal data

C₂₁H₁₇FN₄O₂S
M _r = 408.46
Monoclinic,
a = 21.9754 (6) Å
b = 14.7215 (5) Å
c = 16.2447 (4) Å
β = 132.022 (2)°
V = 3904.1 (2) Å³
Z = 8
Mo Kα radiation
μ = 0.20 mm⁻¹
T = 296 K
0.48 × 0.45 × 0.41 mm

Data collection

Stoe IPDS2 diffractometer
Absorption correction: integration (X-RED32; Stoe & Cie, 2002 ▶) T _min = 0.910, T _max = 0.922
27187 measured reflections
4444 independent reflections
3438 reflections with I > 2σ(I)
R _int = 0.031

Refinement

R[F ² > 2σ(F ²)] = 0.040
wR(F ²) = 0.111
S = 1.04
4444 reflections
302 parameters
4 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.21 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Data collection: X-AREA (Stoe & Cie, 2002 ▶); cell refinement: X-AREA; data reduction: X-RED32 (Stoe & Cie, 2002 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809012677/ng2568sup1.cif

e-65-o1009-sup1.cif^{(27.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809012677/ng2568Isup2.hkl

e-65-o1009-Isup2.hkl^{(213.4KB, hkl)}

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
N1—H1⋯O1ⁱ	0.86	1.96	2.789 (2)	161
N2—H2A⋯S1	0.86	2.52	2.925 (2)	110
C17—H17A⋯O2ⁱⁱ	0.97	2.48	3.336 (3)	147
C20B—H20B⋯F1ⁱⁱⁱ	0.93	2.37	3.284 (10)	168
C14—H14⋯Cg2ⁱⁱⁱ	0.93	2.66	3.371 (2)	134

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) . Cg2 is the centroid of the N1/C1/C6–C8 ring.

Acknowledgments

The authors acknowledge the Faculty of Arts and Sciences, Ondokuz Mayıs University, Turkey, for the use of the Stoe IPDS2 diffractometer (purchased under grant F.279 of the University Research Fund).

supplementary crystallographic information

Comment

Efforts to design, synthesize and screen new molecules that would mimic the actions of currently available chemotherapeutics have resulted in numerous promising candidates incorporating the 4-thiazolidinone system. Many 4-thiazolidinone derivatives have been shown to exhibit bactericidal (Bonde & Gaikwad, 2004; Kline et al., 2008), fungicidal (Çapan et al., 1999) antitubercular (Ulusoy, 2002; Küçükgüzel et al., 2002; Güzel et al., 2006) and anticancer (Zhou et al., 2008) properties. Furthermore the structure of 4-thiazolidinones obtained from asymmetric thiourea derivatives has been frequently discussed due to the formation of regio-isomers involving 2- and 3-positions of the thiazolidinone ring depending upon the relative nucleophilic strengths of the thioamide N atoms (Ottanà et al., 2005; Kline et al., 2008). The nitrogen involved in ene-thiolization (R₁N₁=CSH—N₂HR₂/R₁N₁HCSH=N₂R₂) determines the regiochemical outcome of the cyclization. In this context, the title compound (2) was prepared from a thiosemicarbazide precursor (1) which may be regarded as an asymmetric thiourea analogue in an attempt to obtain a new molecule with antimicrobial action and to establish its definite structure. Thus spectroscopic and X-ray diffraction studies were carried out on (2) to determine the position of the 5-fluoro-3-phenyl-2-indolylcarbonylamino residue and the geometry about the C=N double bond.

In the title compound, (2), (Fig. 1), 1H-indole ring is essentially planar, with a maximum deviation of -0.009 (1) Å for C8. The nine-membered indole ring makes dihedral angles of 54.75 (9) and 14.90 (9) °, respectively, with the phenyl ring (C9–C14) and the 2,5-dihydro-1,3-thiazole ring (S1/N4/C16–C18). The dihedral angle between the (C9–C14) and (S1/N4/C16–C18) rings is 69.15 (9)°.

In the molecule, intramolecular N—H···S hydrogen bonding interactions generate S(5) ring motifs. In the crystal, the two independent molecules are linked into a dimer by two N—H···O hydrogen bonds, forming a R₂²(10) ring motif (Fig. 2). The crystal structure, is further stabilized by intermolecular C—H···π [Cg1 and Cg2 are centroids of the S1/N4/C16–C18 and N1/C1/C6–C8 rings, respectively (Table 1)] and π–π interactions [Cg1···Cg2(x, -y, 1/2 + z) = 3.6791 (10) Å].

Experimental

A mixture of 4-allyl-1-[(5-fluoro-3-phenyl-1H-indol-2-yl)carbonyl]-3-\ thiosemicarbazide (1) (0.0025 mol), ethyl bromoacetate (0.0025 mol) and fused sodium acetate (0.01 mol) in absolute ethanol (15 ml) was heated under reflux for 3 h. The solid thus obtained (2) was filtered, dried and purified by recrystallization from a mixture of ethanol: chloroform [Yield: 63.7%, m.p.: 535–538 K]. IR (KBr) ν = 3309, 3247 (N—H), 1716 (C=O), 1654 (C=O), 1608 (C=N) cm^-1; ¹H-NMR (DMSO-d₆, 500 MHz) δ = 4.05 (2H, s, S—CH₂), 4.24 (2H, s*, N—CH₂CH=CH₂), 5.12 (2H, s*, N—CH₂CH=CH₂), 5.81 (1H, s*, N—CH₂CH=CH₂), 7.11 (1H, dt, J = 9.1, 2.4 Hz, H6-indole), 7.15 (1H, d*, J = 9.3 Hz, H4-indole), 7.36 (1H, s*, 3-C₆H₅ (H4)-indole), 7.49–7.46 (5H, m, H7, 3-C₆H₅ (H2, H6, H3, H5)-indole), 9.78 (1H, s, CONH), 11.87 (1H, s, NH-indole) p.p.m. (* = broad). Analysis calculated for C₂₁H₁₇FN₄O₂S: C 61.75, H 4.20, N 13.72%. Found: C 61.84, H4.87, N 13.69%.