4-Carbethoxy-1-[4-(N,N-dimethylamino)benzoyl]thiosemicarbazide

Hriday Bera; Anton V Dolzhenko; Geok Kheng Tan; Lip Lin Koh; Wai Keung Chui

doi:10.1107/S1600536810015576

. 2010 Apr 30;66(Pt 5):o1241. doi: 10.1107/S1600536810015576

4-Carbethoxy-1-[4-(N,N-dimethylamino)benzoyl]thiosemicarbazide

Hriday Bera ^a, Anton V Dolzhenko ^a,^*, Geok Kheng Tan ^b, Lip Lin Koh ^b, Wai Keung Chui ^a

PMCID: PMC2979162 PMID: 21579260

Abstract

The molecular structure of the title compound, C₁₃H₁₈N₄O₃S, (systematic name: ethyl N-{2-[4-(dimethylamino)benzoyl]hydrazinethiocarbonyl}carbamate) is stabilized by intramolecular N—H⋯O=C hydrogen bonding arranged in an S(6) graph-set motif. In the crystal, inversion dimers connected via intermolecular N—H⋯S=C hydrogen bonds [R ₂ ²(8) graph-set motif] form sheets parallel to the ( Inline graphic 21) plane. Dimers are also formed by the molecules via weak intermolecular N—H⋯S=C hydrogen bonds [R ₂ ²(10) graph-set motif] connecting the sheets.

Related literature

For examples of bioactive 1,4-diacyl substituted thiosemicarbazides and their metal complexes, see: Angelusiu et al. (2009 ▶); Cunha et al. (2007 ▶); Qandil et al. (2006 ▶). For 4-aroyl-1-[4-(N,N-dimethylamino)benzoyl]thiosemicarbazides as high affinity anion receptors, see: Liu & Jiang (2008 ▶). For the structures of related carbethoxythioureas, see: Dolzhenko et al. (2010a ▶,b ▶). For the structures of related 1,4-diacyl thiosemicarbazides, see: Ali et al. (2004 ▶); Xue et al. (2006 ▶); Yamin & Yusof (2003 ▶); Yusof et al. (2003 ▶). For the graph-set analysis of hydrogen bonding, see: Bernstein et al. (1995 ▶).

Experimental

Crystal data

C₁₃H₁₈N₄O₃S
M _r = 310.37
Triclinic,
a = 7.876 (4) Å
b = 8.184 (4) Å
c = 12.086 (6) Å
α = 82.290 (12)°
β = 74.769 (11)°
γ = 84.469 (11)°
V = 743.3 (7) Å³
Z = 2
Mo Kα radiation
μ = 0.23 mm⁻¹
T = 100 K
0.24 × 0.10 × 0.08 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2001 ▶) T _min = 0.946, T _max = 0.982
5201 measured reflections
3379 independent reflections
2839 reflections with I > 2σ(I)
R _int = 0.031

Refinement

R[F ² > 2σ(F ²)] = 0.081
wR(F ²) = 0.218
S = 1.18
3379 reflections
205 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.84 e Å⁻³
Δρ_min = −0.45 e Å⁻³

Data collection: SMART (Bruker, 2001 ▶); cell refinement: SAINT (Bruker, 2001 ▶); 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.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810015576/ds2029sup1.cif

e-66-o1241-sup1.cif^{(18.6KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810015576/ds2029Isup2.hkl

e-66-o1241-Isup2.hkl^{(165.7KB, 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—H1N⋯S1ⁱ	0.82 (6)	2.53 (6)	3.342 (3)	173 (5)
N3—H3N⋯S1ⁱⁱ	0.80 (4)	2.64 (5)	3.385 (4)	156 (4)
N2—H2N⋯O2	0.86 (5)	2.02 (5)	2.653 (4)	130 (4)

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

Acknowledgments

This work was supported by the National Medical Research Council, Singapore (NMRC/NIG/0019/2008).

supplementary crystallographic information

Comment

1,4-Diacyl substituted thiosemicarbazides and their metal complexes have been demonstrated to possess a potent antimicrobial activity (Angelusiu et al., 2009; Cunha et al., 2007; Qandil et al., 2006). In continuation of our structural investigations of the carbethoxythioureas derivatives (Dolzhenko et al., 2010a,b), we report herein molecular and crystal structure of 4-carbethoxy-1-[4-(N,N-dimethylamino)benzoyl]thiosemicarbazide (Figure 1 and 2). The compound is a structural analogue of 4-aroyl-1-[4-(N,N-dimethylamino)benzoyl]thiosemicarbazides reported recently as high affinity anion receptors (Liu & Jiang, 2008).

4-Carbethoxy-1-[4-(N,N-dimethylamino)benzoyl]thiosemicarbazide was prepared by nucleophilic addition of 4-(N,N-dimethylamino)benzhydrazide to ethoxycarbonyl isothiocyanate in DMF at room temperature (Figure 3).

The molecule of 4-carbethoxy-1-[4-(N,N-dimethylamino)benzoyl]thiosemicarbazide adopts similar to the previously reported (Ali et al., 2004; Xue et al., 2006; Yamin & Yusof, 2003;. Yusof et al., 2003) for the related 1,4-diacyl substituted thiosemicarbazides configuration with the thiocarbonyl group pointed to the side opposite of the carbonyl groups. In the thiourea fragment, (E)- and (Z)-configurations observed across the C4—N1 and C4—N2 bonds, respectively. This configuration is stabilized by the strong intramolecular hydrogen bonding between N(2)—H and O2═C3 arranged in the S(6) graph-set motif (Bernstein et al., 1995).

The thiourea C4—N2 bond is significantly shorter (1.315 (5) Å) than other C—N bonds of the molecule. The planarity of the molecule is affected by some twisting at the hydrazine N2—N3 fragment [—C4—N2—N3—C6— torsion angle is 166.5 (33)°].

In the crystal, the molecules form sheets parallel to the (121) plane (Figure 2). In the sheets, atom N1 of one molecule is involved in a intermolecular N(1)—H···S═C interaction with the thiocarbonyl atom S1 of adjacent molecule making pair with the R₂²(8) graph-set motif. Dimmers are also formed by molecules via week intermolecular N(3)—H···S═C hydrogen bonds arranged in R₂²(10)graph-set motifs connecting the sheets between each other.

Experimental

To a fine suspension of 4-(N,N-dimethylamino)benzhydrazide in (0.54 g, 3.0 mmol) in anhydrous DMF (4 ml), ethoxycarbonyl isothiocyanate (0.37 ml, 3.3 mmol) was added. After stirring the mixture for 5 h at ambient temperature, cold water (50 ml) was added. The precipitated product was filtered, washed with cold water and recrystallized from toluene. Yield 0.83 g (89%), m.p. 201 °C (PhMe).

¹H NMR (300 MHz, DMSO-d₆): δ 1.26 (t, 3H, CH₃, J 7.2 Hz), 2.99 (s, 6H, N(CH₃)₂), 4.21 (q, 2H, CH₂, J 7.2 Hz), 6.74 (d, 2H, Ar, J 8.7 Hz), 7.78 (d, 2H, Ar, J 8.7 Hz), 10.56 (s, 1H, NH), 11.34 (s, 1H, NH), 11.41 (s, 1H, NH).

¹³C NMR (75 MHz, DMSO-d₆): δ 15.2, 40.1 (2 C), 62.7, 111.3 (2 C), 118.6, 129.6 (2 C), 153.1, 153.8, 165.0, 179.8.