Benznidazole

José Lamartine Soares-Sobrinho; Marcílio S S Cunha-Filho; Pedro José Rolim Neto; Juan J Torres-Labandeira; Bruno Dacunha-Marinho

doi:10.1107/S1600536808005023

. 2008 Feb 27;64(Pt 3):o634. doi: 10.1107/S1600536808005023

Benznidazole

José Lamartine Soares-Sobrinho ^a, Marcílio S S Cunha-Filho ^b, Pedro José Rolim Neto ^a, Juan J Torres-Labandeira ^b, Bruno Dacunha-Marinho ^c,^*

PMCID: PMC2960770 PMID: 21201965

Abstract

The conformation of the title compound [systematic name: N-benzyl-2-(2-nitroimidazol-1-yl)acetamide], C₁₂H₁₂N₄O₃, can be described in terms of the relative orientation of three planar fragments, the imidazol group (A), benzyl group (B), and the acetamide fragment (C), with corresponding dihedral angles: A/C = 88.17 (4), B/C = 67.12 (5) and A/B = 21.11 (4)°. The crystal packing is enhanced by a network of strong intermolecular N—H⋯O hydrogen bonds.

Related literature

For related literature, see: Coura & Castro (2002 ▶); Lamas et al. (2006 ▶); Morilla et al. (2004 ▶); Silva et al. (2007 ▶).

Experimental

Crystal data

C₁₂H₁₂N₄O₃
M _r = 260.26
Monoclinic,
a = 4.65560 (10) Å
b = 10.9113 (2) Å
c = 11.7681 (3) Å
β = 90.6680 (10)°
V = 597.76 (2) Å³
Z = 2
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 100 (2) K
0.34 × 0.16 × 0.12 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2001 ▶) T _min = 0.861, T _max = 0.987
11597 measured reflections
1287 independent reflections
1216 reflections with I > 2σ(I)
R _int = 0.012

Refinement

R[F ² > 2σ(F ²)] = 0.025
wR(F ²) = 0.066
S = 1.08
1287 reflections
176 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.14 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: APEX2; data reduction: APEX2; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: Mercury (Macrae et al., 2006 ▶) and ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶) and PLATON (Spek, 2003 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808005023/om2213sup1.cif

e-64-0o634-sup1.cif^{(16.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808005023/om2213Isup2.hkl

e-64-0o634-Isup2.hkl^{(62.2KB, hkl)}

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

Enhanced figure: interactive version of Fig. 3

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N8—H8⋯O10ⁱ	0.835 (19)	2.037 (18)	2.837 (2)	160.2 (17)

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank LAFEPE/Brazil, CNPq/Brazil and Xunta de Galicia (project No. PGIDT01BIO20302PR) for supporting this work.

supplementary crystallographic information

Comment

The title compound, Benznidazole, is the drug of choice in the treatment of Chagas disease, a protozoan infection caused by the parasite Trypanosoma cruzi. This illness constitutes a major public health problem for developing nations, affecting sundries Latin America countries, being considered a neglected disease according to World Health Organization (Coura & Castro, 2002; Lamas et al., 2006). In spite of the epidemiological importance of this disease, currently the only available therapeutic agent is Benznidazole, especially effective in the acute phase of infection (Morilla et al., 2004).

The conformation of the title compound (Fig. 1) can be described by the mutual orientation of three approximately planar fragments, A, B and C: one imidazole group (fragment A: N12, C13, N14, C15, C16, N17, O18 and O19 atoms) for which the maximum deviation from the least-squares plane is -0.067 (1) Å, the benzene group (fragment B: C1, C2, C3, C4, C5, C6 and C7 atoms) whose maximum deviation from the mentioned planarity is -0.013 (2), and the central acetamide (fragment C: N8, C9, O10 and C11 atoms), with a deviation of 0.024 (1) Å. The corresponding dihedral angles are: A/C = 88.17 (4)°, B/C = 67.12 (5)° and A/B = 21.11 (4)°.

The strategy of self-assembly through weak interactions is of central importance for efficient and specific biological reactions. In our case we can find one strong intermolecular O···HN hydrogen bond between N(8)–H(8) and O(10) that almost lies along the "a" axis (Fig. 2).

Experimental

Benznidazole was supplied by Laboratório Farmacêutico do Estado de Pernambuco/LAFEPE batch 13871(Recife, Brazil). Purity was estimated by differential scanning calorimetry (DSC-50 Shimadzu) and high-performance liquid chromatography (HPLC Shimadzu) and found to be 99.9% (Silva et al., 2007). Yellow crystals suitable for X-ray analysis were grown from a solution of methanol and acetonitrile (1:1 v/v) at 298 K over a period of a few days in air.

Data collection: APEX2 (Bruker, 2007); cell refinement: APEX2 (Bruker, 2007); data reduction: APEX2 (Bruker, 2007); Absorption correction: SADABS (Bruker, 2001); program used to solve structure: SIR97 (Altomare et al., 1999); program used to refinement structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997) and Mercury (Macrae et al., 2006); software used to prepare material for publication: WinGX (Farrugia, 1999); geometric calculations: PLATON (Spek, 2003).