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Acta Cryst. (2010). E66, o1241    [ doi:10.1107/S1600536810015576 ]

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

H. Bera, A. V. Dolzhenko, G. K. Tan, L. L. Koh and W. K. Chui

Abstract top

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 [R22(8) graph-set motif] form sheets parallel to the (\overline{1}21) plane. Dimers are also formed by the molecules via weak intermolecular N-H...S=C hydrogen bonds [R22(10) graph-set motif] connecting the sheets.

Comment top

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.

Related literature top

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 top

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.

Refinement top

All the H atoms attached to the carbon atoms were constrained in a riding motion approximation [0.95 Å for Caryl—H, 0.99 Å for methylenic protons and 0.98 Å for methyl groups; Uiso(H) = 1.2Ueq(Caryl), Uiso(H) = 1.2Ueq(Cmethylenic) and Uiso(H) = 1.5Ueq(Cmethyl)] while the N-bound H atoms were located in a difference map and refined freely.

Computing details top

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); 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 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of 4-carbethoxy-1-[4-(N,N-dimethylamino)benzoyl]thiosemicarbazide, showing the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
[Figure 2] Fig. 2. Crystal packing in the cell (view along axis c)
[Figure 3] Fig. 3. Synthesis of 4-carbethoxy-1-[4-(N,N-dimethylamino)benzoyl]thiosemicarbazide
Ethyl N-{2-[4-(dimethylamino)benzoyl]hydrazinethiocarbonyl}carbamate top
Crystal data top
C13H18N4O3SZ = 2
Mr = 310.37F(000) = 328
Triclinic, P1Dx = 1.387 Mg m−3
Hall symbol: -P 1Melting point: 474 K
a = 7.876 (4) ÅMo Kα radiation, λ = 0.71073 Å
b = 8.184 (4) ÅCell parameters from 644 reflections
c = 12.086 (6) Åθ = 2.5–27.4°
α = 82.290 (12)°µ = 0.23 mm−1
β = 74.769 (11)°T = 100 K
γ = 84.469 (11)°Rod, colourless
V = 743.3 (7) Å30.24 × 0.10 × 0.08 mm
Data collection top
Bruker SMART APEX CCD
diffractometer		3379 independent reflections
Radiation source: fine-focus sealed tube2839 reflections with I > 2σ(I)
graphiteRint = 0.031
φ and ω scansθmax = 27.5°, θmin = 1.8°
Absorption correction: multi-scan
(SADABS; Sheldrick, 2001)		h = −9→10
Tmin = 0.946, Tmax = 0.982k = −10→10
5201 measured reflectionsl = −12→15
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.081Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.218H atoms treated by a mixture of independent and constrained refinement
S = 1.18 w = 1/[σ2(Fo2) + (0.0987P)2 + 1.3625P]
where P = (Fo2 + 2Fc2)/3
3379 reflections(Δ/σ)max < 0.001
205 parametersΔρmax = 0.84 e Å−3
0 restraintsΔρmin = −0.45 e Å−3
Crystal data top
C13H18N4O3Sγ = 84.469 (11)°
Mr = 310.37V = 743.3 (7) Å3
Triclinic, P1Z = 2
a = 7.876 (4) ÅMo Kα radiation
b = 8.184 (4) ŵ = 0.23 mm−1
c = 12.086 (6) ÅT = 100 K
α = 82.290 (12)°0.24 × 0.10 × 0.08 mm
β = 74.769 (11)°
Data collection top
Bruker SMART APEX CCD
diffractometer		3379 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 2001)		2839 reflections with I > 2σ(I)
Tmin = 0.946, Tmax = 0.982Rint = 0.031
5201 measured reflectionsθmax = 27.5°
Refinement top
R[F2 > 2σ(F2)] = 0.081H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.218Δρmax = 0.84 e Å−3
S = 1.18Δρmin = −0.45 e Å−3
3379 reflectionsAbsolute structure: ?
205 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2σ(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) top
xyzUiso*/Ueq
S10.25106 (11)0.89905 (11)1.00357 (7)0.0123 (3)
O10.6976 (3)1.2062 (3)0.7276 (2)0.0147 (6)
O20.4814 (3)1.1658 (3)0.6437 (2)0.0152 (6)
O30.1155 (3)0.9455 (3)0.6162 (2)0.0146 (6)
N10.4741 (4)1.0685 (4)0.8327 (3)0.0106 (6)
H1N0.534 (7)1.072 (7)0.878 (5)0.037 (15)*
N20.2296 (4)0.9931 (4)0.7882 (3)0.0123 (6)
H2N0.262 (6)1.043 (6)0.719 (4)0.017 (11)*
N30.0781 (4)0.9079 (4)0.8084 (3)0.0138 (7)
H3N0.005 (6)0.926 (5)0.866 (4)0.011 (10)*
N4−0.6011 (4)0.5754 (4)0.7533 (3)0.0218 (8)
C10.9562 (5)1.3511 (5)0.6447 (3)0.0151 (8)
H1A0.91561.43540.69790.023*
H1B1.03411.39970.57300.023*
H1C1.02071.25960.68030.023*
C20.7995 (5)1.2877 (5)0.6182 (3)0.0138 (7)
H2A0.72741.38000.58790.017*
H2B0.83851.20830.56010.017*
C30.5467 (5)1.1491 (4)0.7259 (3)0.0109 (7)
C40.3184 (4)0.9900 (4)0.8667 (3)0.0119 (7)
C60.0248 (4)0.8950 (4)0.7109 (3)0.0109 (7)
C7−0.1384 (4)0.8092 (4)0.7270 (3)0.0108 (7)
C8−0.2115 (5)0.8174 (4)0.6328 (3)0.0122 (7)
H8−0.15580.87780.56190.015*
C9−0.3619 (5)0.7403 (5)0.6401 (3)0.0137 (7)
H9−0.40790.74730.57430.016*
C10−0.4491 (5)0.6506 (4)0.7447 (3)0.0127 (7)
C11−0.3746 (5)0.6417 (5)0.8393 (3)0.0145 (7)
H11−0.42950.58110.91040.017*
C12−0.2221 (5)0.7201 (5)0.8304 (3)0.0124 (7)
H12−0.17420.71290.89550.015*
C13−0.6896 (5)0.4845 (5)0.8622 (4)0.0228 (9)
H13A−0.60840.39620.88530.034*
H13B−0.79330.43630.85270.034*
H13C−0.72660.56000.92190.034*
C14−0.6706 (5)0.5756 (5)0.6535 (3)0.0172 (8)
H14A−0.66490.68610.61030.026*
H14B−0.79350.54560.67890.026*
H14C−0.60040.49530.60370.026*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0110 (4)0.0190 (5)0.0080 (4)−0.0039 (3)−0.0034 (3)−0.0013 (3)
O10.0134 (12)0.0172 (13)0.0144 (13)−0.0080 (10)−0.0040 (10)0.0009 (10)
O20.0169 (13)0.0166 (13)0.0141 (13)−0.0069 (10)−0.0066 (10)0.0008 (10)
O30.0172 (13)0.0185 (13)0.0092 (12)−0.0073 (10)−0.0032 (10)−0.0018 (10)
N10.0119 (14)0.0123 (14)0.0092 (14)−0.0051 (11)−0.0045 (12)−0.0004 (11)
N20.0122 (14)0.0179 (15)0.0072 (14)−0.0068 (12)−0.0028 (11)0.0024 (12)
N30.0067 (13)0.0220 (17)0.0128 (16)−0.0060 (12)−0.0001 (12)−0.0032 (13)
N40.0201 (17)0.0303 (19)0.0176 (17)−0.0149 (15)−0.0078 (14)0.0034 (14)
C10.0134 (16)0.0133 (17)0.0183 (19)−0.0044 (13)−0.0034 (14)0.0004 (14)
C20.0167 (17)0.0143 (17)0.0107 (17)−0.0068 (14)−0.0019 (14)−0.0010 (13)
C30.0129 (16)0.0051 (15)0.0149 (17)−0.0016 (12)−0.0018 (13)−0.0045 (12)
C40.0110 (16)0.0113 (16)0.0133 (17)0.0005 (13)−0.0031 (13)−0.0024 (13)
C60.0109 (15)0.0101 (16)0.0122 (17)−0.0015 (13)−0.0016 (13)−0.0050 (13)
C70.0091 (15)0.0122 (16)0.0104 (16)−0.0028 (13)−0.0004 (13)−0.0012 (13)
C80.0130 (16)0.0089 (16)0.0142 (17)0.0012 (13)−0.0012 (13)−0.0048 (13)
C90.0164 (17)0.0180 (18)0.0108 (17)−0.0025 (14)−0.0078 (14)−0.0064 (14)
C100.0129 (16)0.0119 (16)0.0144 (18)−0.0030 (13)−0.0040 (14)−0.0025 (13)
C110.0159 (17)0.0163 (18)0.0106 (17)−0.0069 (14)−0.0024 (14)0.0028 (14)
C120.0111 (16)0.0180 (18)0.0096 (16)−0.0035 (13)−0.0049 (13)−0.0004 (13)
C130.0180 (19)0.025 (2)0.026 (2)−0.0121 (16)−0.0032 (16)−0.0026 (17)
C140.0189 (18)0.0167 (18)0.021 (2)−0.0042 (14)−0.0125 (15)−0.0029 (15)
Geometric parameters (Å, °) top
S1—C41.690 (4)C2—H2A0.9900
O1—C31.325 (4)C2—H2B0.9900
O1—C21.465 (4)C6—C71.479 (5)
O2—C31.219 (4)C7—C121.394 (5)
O3—C61.221 (4)C7—C81.396 (5)
N1—C31.374 (5)C8—C91.372 (5)
N1—C41.379 (4)C8—H80.9500
N1—H1N0.82 (6)C9—C101.414 (5)
N2—C41.315 (5)C9—H90.9500
N2—N31.390 (4)C10—C111.407 (5)
N2—H2N0.86 (5)C11—C121.389 (5)
N3—C61.371 (5)C11—H110.9500
N3—H3N0.80 (4)C12—H120.9500
N4—C101.372 (5)C13—H13A0.9800
N4—C141.450 (5)C13—H13B0.9800
N4—C131.458 (5)C13—H13C0.9800
C1—C21.507 (5)C14—H14A0.9800
C1—H1A0.9800C14—H14B0.9800
C1—H1B0.9800C14—H14C0.9800
C1—H1C0.9800
C3—O1—C2116.3 (3)O3—C6—C7123.2 (3)
C3—N1—C4127.1 (3)N3—C6—C7116.7 (3)
C3—N1—H1N112 (4)C12—C7—C8118.4 (3)
C4—N1—H1N121 (4)C12—C7—C6123.7 (3)
C4—N2—N3122.1 (3)C8—C7—C6117.9 (3)
C4—N2—H2N124 (3)C9—C8—C7121.6 (3)
N3—N2—H2N114 (3)C9—C8—H8119.2
C6—N3—N2114.1 (3)C7—C8—H8119.2
C6—N3—H3N119 (3)C8—C9—C10120.6 (3)
N2—N3—H3N114 (3)C8—C9—H9119.7
C10—N4—C14121.0 (3)C10—C9—H9119.7
C10—N4—C13120.2 (3)N4—C10—C11121.3 (3)
C14—N4—C13118.7 (3)N4—C10—C9121.0 (3)
C2—C1—H1A109.5C11—C10—C9117.7 (3)
C2—C1—H1B109.5C12—C11—C10121.0 (3)
H1A—C1—H1B109.5C12—C11—H11119.5
C2—C1—H1C109.5C10—C11—H11119.5
H1A—C1—H1C109.5C11—C12—C7120.7 (3)
H1B—C1—H1C109.5C11—C12—H12119.7
O1—C2—C1106.0 (3)C7—C12—H12119.7
O1—C2—H2A110.5N4—C13—H13A109.5
C1—C2—H2A110.5N4—C13—H13B109.5
O1—C2—H2B110.5H13A—C13—H13B109.5
C1—C2—H2B110.5N4—C13—H13C109.5
H2A—C2—H2B108.7H13A—C13—H13C109.5
O2—C3—O1126.1 (3)H13B—C13—H13C109.5
O2—C3—N1125.2 (3)N4—C14—H14A109.5
O1—C3—N1108.7 (3)N4—C14—H14B109.5
N2—C4—N1116.4 (3)H14A—C14—H14B109.5
N2—C4—S1123.9 (3)N4—C14—H14C109.5
N1—C4—S1119.7 (3)H14A—C14—H14C109.5
O3—C6—N3120.0 (3)H14B—C14—H14C109.5
C4—N2—N3—C6−166.5 (3)N3—C6—C7—C8169.8 (3)
C3—O1—C2—C1176.1 (3)C12—C7—C8—C90.0 (5)
C2—O1—C3—O2−4.1 (5)C6—C7—C8—C9179.5 (3)
C2—O1—C3—N1176.4 (3)C7—C8—C9—C100.6 (5)
C4—N1—C3—O21.2 (6)C14—N4—C10—C11−175.8 (3)
C4—N1—C3—O1−179.3 (3)C13—N4—C10—C110.3 (6)
N3—N2—C4—N1174.8 (3)C14—N4—C10—C94.3 (6)
N3—N2—C4—S1−6.0 (5)C13—N4—C10—C9−179.5 (4)
C3—N1—C4—N2−0.2 (5)C8—C9—C10—N4178.9 (3)
C3—N1—C4—S1−179.4 (3)C8—C9—C10—C11−0.9 (5)
N2—N3—C6—O35.2 (5)N4—C10—C11—C12−179.1 (4)
N2—N3—C6—C7−178.5 (3)C9—C10—C11—C120.8 (5)
O3—C6—C7—C12165.6 (4)C10—C11—C12—C7−0.3 (6)
N3—C6—C7—C12−10.6 (5)C8—C7—C12—C11−0.1 (5)
O3—C6—C7—C8−13.9 (5)C6—C7—C12—C11−179.6 (3)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···S1i0.82 (6)2.53 (6)3.342 (3)173 (5)
N3—H3N···S1ii0.80 (4)2.64 (5)3.385 (4)156 (4)
N2—H2N···O20.86 (5)2.02 (5)2.653 (4)130 (4)
Symmetry codes: (i) −x+1, −y+2, −z+2; (ii) −x, −y+2, −z+2.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···S1i0.82 (6)2.53 (6)3.342 (3)173 (5)
N3—H3N···S1ii0.80 (4)2.64 (5)3.385 (4)156 (4)
N2—H2N···O20.86 (5)2.02 (5)2.653 (4)130 (4)
Symmetry codes: (i) −x+1, −y+2, −z+2; (ii) −x, −y+2, −z+2.
Acknowledgements top

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

references
References top

Ali, H., Yusof, M. S., Khamis, N. A., Mardi, A. S. & Yamin, B. M. (2004). Acta Cryst. E60, o1656–o1658.

Angelusiu, M. V., Almajan, G. L., Rosu, T., Negoiu, M., Almajan, E.-R. & Roy, J. (2009). Eur. J. Med. Chem. 44, 3323–3329.

Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N. L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555–1573.

Bruker (2001). SMART and SAINT. Bruker AXS GmbH, Karlsruhe, Germany.

Cunha, S., Macedo, F. C. Jr, Costa, G. A. N., Rodrigues, M. T. Jr, Verde, R. B. V., de Souza Neta, L. C., Vencato, I., Lariucci, C. & Sa, F. P. (2007). Monatsh. Chem. 138, 511–516.

Dolzhenko, A. V., Tan, G. K., Koh, L. L., Dolzhenko, A. V. & Chui, W. K. (2010a). Acta Cryst. E66, o425.

Dolzhenko, A. V., Tan, G. K., Koh, L. L., Dolzhenko, A. V. & Chui, W. K. (2010b). Acta Cryst. E66, o549–o550.

Liu, W.-X. & Jiang, Y.-B. (2008). J. Org. Chem. 73, 1124-1127.

Qandil, A. M., Tumah, H. N. & Hassan, M. A. (2006). Acta Pharm. Sci. 48, 95–107.

Sheldrick, G. M. (2001). SADABS. University of Göttingen, Germany.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Xue, S.-J., Bian, W.-D., Wang, Q.-D. & Chai, A. (2006). Acta Cryst. E62, o4842–o4843.

Yamin, B. M. & Yusof, M. S. M. (2003). Acta Cryst. E59, o124–o126.

Yusof, M. S. M., Yamin, B. M. & Shamsuddin, M. (2003). Acta Cryst. E59, o810–o811.