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Acta Crystallogr Sect E Struct Rep Online. 2009 March 1; 65(Pt 3): o621.
Published online 2009 February 28. doi:  10.1107/S1600536809006527
PMCID: PMC2968597

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

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

An external file that holds a picture, illustration, etc.
Object name is e-65-0o621-scheme1.jpg

Experimental

Crystal data

  • C14H21N3OS
  • M r = 279.40
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-0o621-efi1.jpg
  • 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 [triangle]) 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
  • Δρmax = 0.68 e Å−3
  • Δρmin = −0.32 e Å−3

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

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

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

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

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

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).

Refinement

N-bound hydrogen atoms were located from the difference Fourier map and refined freely; see Table 1. The rest of the hydrogen atoms were positioned geometrically and constrained to refine with the parent atoms with C—H = 0.93–1.00 Å and Uiso(H) = 1.2 or 1.5 Ueq(C). A rotating group model was used for the methyl groups.

Figures

Fig. 1.
Molecular structure of (I) with the atom labeling scheme. Ellipsoids are drawn at the 50% probability level. H atoms are represented as small sphere of arbitrary radii. The enantiomer represented has R configuration at C7.
Fig. 2.
The crystal packing of (I) showing the graph set motifs. Intermolecular interactions are shown as dashed lines. H atoms not involved in hydrogen bondings have been removed for clarity.

Crystal data

C14H21N3OSZ = 2
Mr = 279.40F(000) = 300
Triclinic, P1Dx = 1.237 Mg m3
Hall symbol: -P 1Melting point: 335 K
a = 5.5347 (1) ÅMo Kα radiation, λ = 0.71073 Å
b = 10.6209 (3) ÅCell parameters from 9906 reflections
c = 13.1435 (3) Åθ = 2.3–38.2°
α = 97.935 (1)°µ = 0.21 mm1
β = 98.418 (1)°T = 100 K
γ = 96.293 (1)°Block, colourless
V = 750.30 (3) Å30.54 × 0.32 × 0.15 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer6524 independent reflections
Radiation source: fine-focus sealed tube5896 reflections with I > 2σ(I)
graphiteRint = 0.018
[var phi] and ω scansθmax = 35.0°, θmin = 1.6°
Absorption correction: multi-scan (SADABS; Bruker, 2005)h = −8→8
Tmin = 0.894, Tmax = 0.969k = −16→17
18596 measured reflectionsl = −20→21

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.034Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.096H atoms treated by a mixture of independent and constrained refinement
S = 1.05w = 1/[σ2(Fo2) + (0.0494P)2 + 0.1966P] where P = (Fo2 + 2Fc2)/3
6524 reflections(Δ/σ)max = 0.001
191 parametersΔρmax = 0.68 e Å3
0 restraintsΔρmin = −0.32 e Å3

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K.
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)

xyzUiso*/Ueq
S10.30182 (3)0.806105 (17)0.407445 (14)0.01523 (5)
O10.65430 (10)0.57112 (5)0.62717 (5)0.01802 (10)
N10.87208 (11)0.64109 (6)0.50767 (5)0.01429 (10)
N20.66238 (12)0.66716 (6)0.44588 (5)0.01530 (11)
N30.74599 (12)0.87876 (6)0.52340 (5)0.01701 (11)
C10.95446 (14)0.81565 (7)0.78524 (6)0.01651 (12)
H1A0.82810.75780.80190.020*
C20.96885 (14)0.94657 (7)0.82013 (6)0.01724 (12)
H2A0.85190.97690.86040.021*
C31.15276 (14)1.03429 (7)0.79679 (6)0.01707 (12)
C41.32484 (15)0.98630 (8)0.73933 (6)0.01981 (14)
H4A1.45341.04390.72390.024*
C51.31130 (14)0.85529 (8)0.70412 (6)0.01828 (13)
H5A1.43030.82490.66500.022*
C61.12491 (13)0.76844 (7)0.72571 (5)0.01440 (11)
C71.09656 (13)0.62723 (7)0.67782 (6)0.01577 (12)
H7A1.23280.61340.63690.019*
C80.85365 (13)0.60673 (6)0.60322 (6)0.01385 (11)
C90.58753 (12)0.78460 (6)0.46377 (5)0.01334 (11)
C101.16404 (17)1.17610 (7)0.83421 (6)0.02134 (14)
H10A0.99761.20130.81730.026*
H10B1.27501.22400.79600.026*
C111.25548 (16)1.21505 (8)0.95183 (6)0.02091 (14)
H11A1.14651.16310.98930.025*
C121.5176 (2)1.18766 (13)0.98222 (10)0.0422 (3)
H12A1.56591.20841.05800.063*
H12B1.62901.24020.94850.063*
H12C1.52711.09670.95980.063*
C131.2345 (2)1.35641 (8)0.98524 (8)0.02918 (18)
H13A1.29431.38021.06010.044*
H13B1.06171.37060.97000.044*
H13C1.33391.40910.94700.044*
C141.09915 (18)0.53538 (8)0.75758 (7)0.02360 (15)
H14A1.25810.55210.80440.035*
H14B1.07470.44670.72140.035*
H14C0.96640.54840.79820.035*
H1N20.556 (3)0.6019 (14)0.4190 (11)0.027 (3)*
H1N11.013 (2)0.6698 (13)0.4891 (10)0.024 (3)*
H2N30.888 (3)0.8658 (13)0.5509 (11)0.029 (3)*
H1N30.703 (3)0.9524 (14)0.5348 (11)0.027 (3)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S10.01232 (8)0.01386 (8)0.01930 (9)0.00173 (5)0.00039 (6)0.00418 (6)
O10.0155 (2)0.0151 (2)0.0225 (3)−0.00111 (18)0.00474 (19)0.00054 (19)
N10.0111 (2)0.0143 (2)0.0172 (2)0.00244 (18)0.00100 (19)0.00253 (19)
N20.0134 (2)0.0117 (2)0.0190 (3)0.00211 (19)−0.0017 (2)0.00032 (19)
N30.0137 (2)0.0116 (2)0.0239 (3)0.00168 (19)−0.0009 (2)0.0003 (2)
C10.0146 (3)0.0140 (3)0.0202 (3)0.0002 (2)0.0040 (2)0.0003 (2)
C20.0164 (3)0.0145 (3)0.0197 (3)0.0017 (2)0.0028 (2)−0.0006 (2)
C30.0196 (3)0.0145 (3)0.0151 (3)−0.0006 (2)−0.0012 (2)0.0020 (2)
C40.0206 (3)0.0196 (3)0.0175 (3)−0.0040 (3)0.0034 (2)0.0018 (2)
C50.0153 (3)0.0213 (3)0.0169 (3)−0.0004 (2)0.0033 (2)−0.0002 (2)
C60.0127 (3)0.0145 (3)0.0149 (3)0.0020 (2)0.0002 (2)0.0005 (2)
C70.0147 (3)0.0148 (3)0.0173 (3)0.0043 (2)0.0008 (2)0.0007 (2)
C80.0141 (3)0.0098 (2)0.0168 (3)0.0020 (2)0.0019 (2)−0.0004 (2)
C90.0128 (3)0.0121 (2)0.0152 (3)0.0012 (2)0.0025 (2)0.0026 (2)
C100.0288 (4)0.0131 (3)0.0194 (3)−0.0001 (3)−0.0021 (3)0.0019 (2)
C110.0263 (4)0.0156 (3)0.0185 (3)−0.0009 (3)0.0011 (3)0.0004 (2)
C120.0356 (5)0.0422 (6)0.0389 (6)0.0109 (5)−0.0156 (4)−0.0103 (5)
C130.0385 (5)0.0165 (3)0.0286 (4)−0.0021 (3)0.0034 (4)−0.0032 (3)
C140.0315 (4)0.0181 (3)0.0212 (3)0.0078 (3)0.0000 (3)0.0044 (3)

Geometric parameters (Å, °)

S1—C91.6982 (7)C5—H5A0.9500
O1—C81.2259 (9)C6—C71.5261 (10)
N1—C81.3699 (10)C7—C81.5190 (10)
N1—N21.3927 (9)C7—C141.5270 (11)
N1—H1N10.884 (14)C7—H7A1.0000
N2—C91.3578 (9)C10—C111.5381 (12)
N2—H1N20.855 (15)C10—H10A0.9900
N3—C91.3318 (9)C10—H10B0.9900
N3—H2N30.851 (14)C11—C121.5178 (14)
N3—H1N30.843 (14)C11—C131.5269 (12)
C1—C21.3925 (10)C11—H11A1.0000
C1—C61.4019 (10)C12—H12A0.9800
C1—H1A0.9500C12—H12B0.9800
C2—C31.4002 (11)C12—H12C0.9800
C2—H2A0.9500C13—H13A0.9800
C3—C41.3957 (12)C13—H13B0.9800
C3—C101.5100 (11)C13—H13C0.9800
C4—C51.3947 (11)C14—H14A0.9800
C4—H4A0.9500C14—H14B0.9800
C5—C61.3946 (11)C14—H14C0.9800
C8—N1—N2119.30 (6)N1—C8—C7114.12 (6)
C8—N1—H1N1123.8 (9)N3—C9—N2117.81 (6)
N2—N1—H1N1114.5 (8)N3—C9—S1123.05 (5)
C9—N2—N1119.39 (6)N2—C9—S1119.12 (5)
C9—N2—H1N2119.6 (9)C3—C10—C11113.56 (6)
N1—N2—H1N2115.4 (9)C3—C10—H10A108.9
C9—N3—H2N3121.5 (10)C11—C10—H10A108.9
C9—N3—H1N3118.9 (10)C3—C10—H10B108.9
H2N3—N3—H1N3119.6 (13)C11—C10—H10B108.9
C2—C1—C6120.56 (7)H10A—C10—H10B107.7
C2—C1—H1A119.7C12—C11—C13110.83 (8)
C6—C1—H1A119.7C12—C11—C10111.70 (8)
C1—C2—C3121.12 (7)C13—C11—C10110.21 (7)
C1—C2—H2A119.4C12—C11—H11A108.0
C3—C2—H2A119.4C13—C11—H11A108.0
C4—C3—C2117.97 (7)C10—C11—H11A108.0
C4—C3—C10121.57 (7)C11—C12—H12A109.5
C2—C3—C10120.45 (7)C11—C12—H12B109.5
C5—C4—C3121.16 (7)H12A—C12—H12B109.5
C5—C4—H4A119.4C11—C12—H12C109.5
C3—C4—H4A119.4H12A—C12—H12C109.5
C6—C5—C4120.71 (7)H12B—C12—H12C109.5
C6—C5—H5A119.6C11—C13—H13A109.5
C4—C5—H5A119.6C11—C13—H13B109.5
C5—C6—C1118.45 (7)H13A—C13—H13B109.5
C5—C6—C7120.22 (6)C11—C13—H13C109.5
C1—C6—C7121.14 (6)H13A—C13—H13C109.5
C8—C7—C6104.02 (5)H13B—C13—H13C109.5
C8—C7—C14112.04 (7)C7—C14—H14A109.5
C6—C7—C14113.91 (6)C7—C14—H14B109.5
C8—C7—H7A108.9H14A—C14—H14B109.5
C6—C7—H7A108.9C7—C14—H14C109.5
C14—C7—H7A108.9H14A—C14—H14C109.5
O1—C8—N1121.87 (7)H14B—C14—H14C109.5
O1—C8—C7123.83 (7)
C8—N1—N2—C981.80 (8)C1—C6—C7—C14−59.88 (9)
C6—C1—C2—C30.06 (12)N2—N1—C8—O116.17 (10)
C1—C2—C3—C4−1.36 (11)N2—N1—C8—C7−159.10 (6)
C1—C2—C3—C10179.31 (7)C6—C7—C8—O1−91.51 (8)
C2—C3—C4—C51.40 (12)C14—C7—C8—O131.97 (10)
C10—C3—C4—C5−179.28 (7)C6—C7—C8—N183.65 (7)
C3—C4—C5—C6−0.13 (12)C14—C7—C8—N1−152.87 (6)
C4—C5—C6—C1−1.19 (11)N1—N2—C9—N314.79 (10)
C4—C5—C6—C7173.91 (7)N1—N2—C9—S1−166.70 (5)
C2—C1—C6—C51.22 (11)C4—C3—C10—C11−106.27 (9)
C2—C1—C6—C7−173.83 (7)C2—C3—C10—C1173.03 (10)
C5—C6—C7—C8−112.59 (7)C3—C10—C11—C1262.58 (11)
C1—C6—C7—C862.37 (8)C3—C10—C11—C13−173.75 (8)
C5—C6—C7—C14125.16 (8)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N2—H1N2···O1i0.857 (15)2.029 (15)2.8745 (9)169.0 (14)
N1—H1N1···S1ii0.886 (12)2.495 (13)3.3324 (7)157.8 (11)
N3—H1N3···S1iii0.842 (15)2.577 (15)3.3945 (7)164.1 (14)
C7—H7A···O1ii1.002.443.3501 (9)151
N3—H2N3···Cg10.850 (16)2.870 (14)3.5083 (7)133.4 (12)

Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) x+1, y, z; (iii) −x+1, −y+2, −z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: DN2428).

References

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