(2R)-2-Cinnamoylamino-N-[5-(4-methoxy­phen­yl)-1,3,4-thia­diazol-2-yl]propanamide

Shao-Hua Li; Gang Li; Hui-Ming Huang; Guo-Gang Tu; Cheng-Mei Liu

doi:10.1107/S1600536808027803

. 2008 Sep 6;64(Pt 10):o1887. doi: 10.1107/S1600536808027803

(2R)-2-Cinnamoylamino-N-[5-(4-methoxyphenyl)-1,3,4-thiadiazol-2-yl]propanamide

Shao-Hua Li ^a,^b, Gang Li ^b, Hui-Ming Huang ^b, Guo-Gang Tu ^b,^*, Cheng-Mei Liu ^a,^‡

PMCID: PMC2959345 PMID: 21201099

Abstract

The asymmetric unit of the title compound, C₂₁H₂₀N₄O₃S, contains two independent molecules. The dihedral angles between the two benzene rings are 47.6 (1) and 30.2 (1)°, the corresponding values between the p-methoxybenzene and thiadiazol rings are 12.3 (1) and 24.7 (1)°, respectively, for the two molecules. The conformations of the N—H and C=O bonds are anti with respect to each other. The enone groups show a trans configuration. The crystal structure is stabilized by N—H⋯O and N—H⋯N interactions. The absolute structure could not be determined from the X-ray data but the absolute configuration has been assigned by reference to an unchanging chiral centre in the synthetic procedure.

Related literature

For 1,3,4-thiadiazole scaffold compounds and their biological activity, see: Tu et al. (2008 ▶). For the synthesis, see: Foroumadi et al. (1999 ▶); Levy & Palmer (1942 ▶); Song et al. (1992 ▶). For related structures, see: Fun et al. (2008 ▶); Gowda et al. (2008 ▶) Thiruvalluvar et al. (2008 ▶).

Experimental

Crystal data

C₂₁H₂₀N₄O₃S
M _r = 408.48
Triclinic,
a = 9.082 (3) Å
b = 9.849 (3) Å
c = 13.644 (4) Å
α = 79.587 (4)°
β = 83.253 (4)°
γ = 65.458 (4)°
V = 1090.8 (5) Å³
Z = 2
Mo Kα radiation
μ = 0.18 mm⁻¹
T = 296 (2) K
0.35 × 0.24 × 0.06 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
Absorption correction: none
6219 measured reflections
3553 independent reflections
2735 reflections with I > 2σ(I)
R _int = 0.022

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.097
S = 0.94
3553 reflections
528 parameters
3 restraints
H-atom parameters constrained
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.17 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: APEX2 and SAINT (Bruker, 2004 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: APEX2; software used to prepare material for publication: APEX2 and publCIF (Westrip, 2008 ▶).

Supplementary Material

Crystal structure: contains datablocks I. DOI: 10.1107/S1600536808027803/im2079sup1.cif

e-64-o1887-sup1.cif^{(27.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808027803/im2079Isup2.hkl

e-64-o1887-Isup2.hkl^{(174.2KB, 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
N3—H3A⋯O4	0.86	2.10	2.960 (4)	177
N4—H4A⋯N6ⁱ	0.86	2.17	3.016 (5)	168
N7—H7A⋯O1ⁱⁱ	0.86	2.09	2.944 (4)	171
N8—H8⋯N2	0.86	2.20	3.036 (5)	165

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

supplementary crystallographic information

Comment

In our previous work, 1,3,4-thiadiazole scaffold compounds and their biological activity have been studied (Tu et al., 2008). In view of the importance of these organic materials, the title compound (Fig. 1) was synthesized (Foroumadi et al., 1999; Levy & Palmer 1942; Song et al., 1992) and its crystal structure is reported here. The asymmetric unit of the title compound, C₂₁H₂₀N₄O₃S, contains two independent molecules. The dihedral angles between the p-methoxybenzene and thiadiazol rings is 12.2 (1) ° and 24.7 (1)°, the corresponding values between the two benzene rings are measured to 47.6 (1)° and 30.2 (1)°, respectively, for the two molecules. The conformations of the N—H and C=O bonds are anti with respect to each other. The enone groups are trans configurated. Bond lengths and angles are in normal ranges and comparable to those in related structures (Gowda et al., 2008; Fun et al., 2008; Thiruvalluvar et al., 2008). In the crystal structure, molecules are linked through intermolecular N—H···O hydrogen bonds forming a three-dimensional network (Table 1, Figure 2).

Experimental

N,N-Dicyclohexylcarbodiimide (5.7 mmol) was added to a cooled solution of N-cinnamoyl-D-alanine (5.6 mmol) and N-hydroxysuccinimide (5.6 mmol) in freshly distilled dioxane (30 ml). The reaction mixture was stirred overnight at room temperature. The insoluble material was filtered off and washed with cold dioxane. 2-Amino-5-(4-methoxyphenyl)-1,3,4-thiadiazole (5.5 mmol) was added to the filtrate and the reaction mixture was stirred for 48 hr at room temperature. The solvent was removed under reduced pressure. The residual was dissolved in EtOAc and the insoluble material was filtered off. The filtrate was washed successively with saturated Na₂CO₃ solution (20 ml, x 3), water (20 ml, x 1), 0.1 M HCl (20 ml, x 3) and water (20 ml, x 1). The organic layer was evaporated in vacuo and the residue was recrystallized from methanol (30 ml), yield: 35.2%. Colorless block-shaped single crystals of the title compound suitable for X-ray diffraction analysis precipitated after several days.