1-[2-(4-Isobutyl­phen­yl)propano­yl]thiosemicarbazide

Hoong-Kun Fun; Reza Kia; Samuel Robinson Jebas; K V Sujith; B Kalluraya

doi:10.1107/S1600536809006527

. 2009 Feb 28;65(Pt 3):o621. doi: 10.1107/S1600536809006527

1-[2-(4-Isobutylphenyl)propanoyl]thiosemicarbazide

Hoong-Kun Fun ^a,^*, Reza Kia ^a, Samuel Robinson Jebas ^a, K V Sujith ^b, B Kalluraya ^b

PMCID: PMC2968597 PMID: 21582273

Abstract

In the title compound, C₁₄H₂₁N₃OS, intermolecular N—H⋯O interactions generate ten-membered rings with R ₂ ²(10) ring motifs, whereas N—H⋯S interactions generate eight, 14- and 16-membered rings with R ₂ ²(8), R ₄ ⁴(14) and R ₄ ⁴(16) ring motifs, respectively. There are weak intramolecular N—H⋯π interactions which might influence the conformation of the molecule. The compound has a stereogenic center but the space group is centrosymmetic so the molecule exists as a racemate.

Related literature

For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). For biomedical applications of non-steroidal anti-inflammatory drugs, see, for example; Kawail et al. (2005 ▶); Klasser & Epstein (2005 ▶); Kean & Buchanan (2005 ▶); Nielsen & Bundgaard (1988 ▶); Khan & Akhter (2005 ▶); Zhao et al. (2006 ▶). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 ▶).

Experimental

Crystal data

C₁₄H₂₁N₃OS
M _r = 279.40
Triclinic,
a = 5.5347 (1) Å
b = 10.6209 (3) Å
c = 13.1435 (3) Å
α = 97.935 (1)°
β = 98.418 (1)°
γ = 96.293 (1)°
V = 750.30 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.21 mm⁻¹
T = 100 K
0.54 × 0.32 × 0.15 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2005 ▶) T _min = 0.894, T _max = 0.969
18596 measured reflections
6524 independent reflections
5896 reflections with I > 2σ(I)
R _int = 0.018

Refinement

R[F ² > 2σ(F ²)] = 0.034
wR(F ²) = 0.096
S = 1.05
6524 reflections
191 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.68 e Å⁻³
Δρ_min = −0.32 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT (Bruker, 2005 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809006527/dn2428sup1.cif

e-65-0o621-sup1.cif^{(19.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809006527/dn2428Isup2.hkl

e-65-0o621-Isup2.hkl^{(319.3KB, 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
N2—H1N2⋯O1ⁱ	0.857 (15)	2.029 (15)	2.8745 (9)	169.0 (14)
N1—H1N1⋯S1ⁱⁱ	0.886 (12)	2.495 (13)	3.3324 (7)	157.8 (11)
N3—H1N3⋯S1ⁱⁱⁱ	0.842 (15)	2.577 (15)	3.3945 (7)	164.1 (14)
C7—H7A⋯O1ⁱⁱ	1.00	2.44	3.3501 (9)	151
N3—H2N3⋯Cg1	0.850 (16)	2.870 (14)	3.5083 (7)	133.4 (12)

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) . Cg1 is the centroid of the C1–C6 benzene ring.

Acknowledgments

HKF, RK and SRJ thank the Malaysian Government and Universiti Sains Malaysia for the Science Fund grant No. 305/PFIZIK/613312. RK and SRJ thank Universiti Sains Malaysia for post-doctoral research fellowships. HKF also thanks Universiti Sains Malaysia for the Research University Golden Goose grant No. 1001/PFIZIK/811012.

supplementary crystallographic information

Comment

Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen are widely used in the treatment of pain and inflammation (Kawail et al., 2005; Klasser & Epstein, 2005).In fact, prolonged use of NSAIDs, for example ibuprofen, has been associated with gastrointestinal complications (Kean & Buchanan, 2005). Therefore, synthetic approaches based upon NSAIDs chemical modification have been undertaken with the aim of improving the NSAID safety profile. The utilization of prodrugs to temporarily mask the acidic group of NSAIDs has been proposed as an approach to reduce or suppress the GI toxicity due to the direct contact effect and also to increase their absorption values (Nielsen & Bundgaard, 1988). Ester prodrugs of ibuprofen have been synthesized with this aim (Khan & Akhter, 2005). Ester prodrugs of ibuprofen were synthesized and found to have anti-inflammatory, analgesic and ulcerogenic activities (Zhao et al., 2006). Due to these reasons, we have synthesized the thiosemicarbazide analogue of ibuprofen and report its crystal structure.

The title compound, I, Fig. 1, comprises a single molecule in the asymmetric unit. Intermolecular N—H···O interactions generate ten-membered rings producing R₂²(10) ring motifs, whereas N—H···S interactions generate eight, fourteen, sixteen rings producing R₂²(8), R₄⁴(14) and R₄⁴(16) ring motifs, respectively. (Fig.2) (Bernstein et al., 1995). There is a weak intramolecular N—H···π interaction (Table 1, Cg1 is the centroid of the C1–C6 benzene ring). The compound has a stereogenic center at C7 but the space group is centrosymmetic so the molecule exists as a racemate.

Experimental

A mixture of 2-[2-(4-isobutylphenyl)propanoyl]hydrazine (0.01 mole), potassium thiocyanate (1.9 g, 0.02 mole), conc. HCl (1 ml) and water (20 ml) was refluxed for 3 h. On cooling the solid obtained was collected by filtration, washed with water and dried. Crystals suitable for X-ray analysis were obtained from ethanol by slow evaporation (Yield 62%; m.p. 447 K).