3-[2-(1H-1,3-Benzodiazol-2-yl)eth­yl]-1,3-oxazolidin-2-one

Giovanna Brancatelli; Francesco Nicoló; Sara De Grazia; Anna Maria Monforte; Alba Chimirri

doi:10.1107/S1600536811012256

. 2011 Apr 13;67(Pt 5):o1083. doi: 10.1107/S1600536811012256

3-[2-(1H-1,3-Benzodiazol-2-yl)ethyl]-1,3-oxazolidin-2-one

Giovanna Brancatelli ^a,^*, Francesco Nicoló ^a, Sara De Grazia ^b, Anna Maria Monforte ^b, Alba Chimirri ^b

PMCID: PMC3089160 PMID: 21754405

Abstract

In the title compound, C₁₂H₁₃N₃O₂, the dihedral angle between the oxazolone ring and the benzimidazole unit is 45.0 (5)°, exhibiting a staggered conformation at the Cα—Cβ bond. In the crystal, a strong N—H⋯N hydrogen bond links the molecules into a C(4) chain along the c axis while a C—H⋯O hydrogen-bonding interaction generates a C(5) chain along the a axis, i.e. perpendicular to the other chain.

Related literature

For the therapeutic activity of benzimidazole and oxazolidinone derivatives, see: Niño et al. 2001 ▶; Siva Kumar et al. 2010 ▶; Zappia et al. 2007 ▶. For the drug linezolid [systematic name (S)-N-({3-[3-fluoro-4-(morpholin-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide], see: Brickner et al. (2008 ▶). For asymmetry of the exocyclic angles in oxazolone rings, see: Grassi et al. (2001 ▶). For the structures of benzimidazole and oxazolidine, see: Totsatitpaisan et al. (2008 ▶); Wouters et al. (1997 ▶).

Experimental

Crystal data

C₁₂H₁₃N₃O₂
M _r = 231.25
Monoclinic,
a = 6.0940 (2) Å
b = 18.1570 (6) Å
c = 10.0740 (3) Å
β = 90.696 (1)°
V = 1114.59 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 296 K
0.51 × 0.43 × 0.21 mm

Data collection

Bruker APEXII CCD diffractometer
34135 measured reflections
1951 independent reflections
1830 reflections with I > 2σ(I)
R _int = 0.021

Refinement

R[F ² > 2σ(F ²)] = 0.033
wR(F ²) = 0.089
S = 1.05
1951 reflections
155 parameters
H-atom parameters constrained
Δρ_max = 0.21 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); 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 global, I. DOI: 10.1107/S1600536811012256/bh2341sup1.cif

e-67-o1083-sup1.cif^{(16KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811012256/bh2341Isup2.hkl

e-67-o1083-Isup2.hkl^{(94KB, 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—H1⋯N8ⁱ	0.86	2.08	2.8959 (13)	158
C11—H11A⋯O14ⁱⁱ	0.97	2.53	3.2876 (16)	135

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

Acknowledgments

The authors thank the University of Messina and the MIUR (Ministero dell’Istruzione, dell’Universitá e della Ricerca) for financial support.

supplementary crystallographic information

Comment

Heterocyclic compounds containing 5- or 6-membered rings are important for their diverse biological activities. In particular, the chemistry of oxazolidinone and benzimidazole has received considerable attention owing to their synthetic and biological importance.

Benzimidazole and oxazolidinone derivatives have been studied for the treatment of different pathologies. Their scaffold has been incorporated into a wide variety of therapeutically interesting compounds that show antibacterial, antifungal, antiviral, antineoplastics and cholinergic activity among others (Niño et al., 2001; Siva Kumar et al., 2010; Zappia et al., 2007). Furthermore, the introduction in the pharmaceutical market of Linezolid, an oxazolidin-2-one-based antibacterial drug, attracted the interest of the scientists on this scaffold (Brickner et al., 2008). On the basis of some common properties, such as antibacterial activity, of these two classes of heterocyclic compounds, in this study we synthesized the title molecule, in which the benzimidazole ring is linked to an oxazolidinone scaffold, with the aim to obtain a compound having two different moieties in the same molecular entity, and then a synergism of activity.

The one-pot synthetic route employed to obtain the title compound is depicted in Figure 1. Treatment of the commercially available 2-(2-aminoethyl)-benzimidazole dihydrochloride with dibromoethane and potassium carbonate gave the desired product. The proposed mechanism for the synthesis is shown in Figure 2. The nucleophilic attack of the 2-(2-aminoethyl)-benzimidazole primary amine function on the dibromoethane is followed by oxazolidinone ring formation. An excess of potassium carbonate is necessary both to create the basic medium for the N-alkylation and for the formation of the oxazolidinone moiety.

The molecule crystallizes in the centrosymmetric P2₁/c space group. The asymmetric unit contains one molecule, shown in Figure 3. The dihedral angle between the oxazolone ring and the benzimidazole unit is 45.0 (5)°, exhibiting a staggered conformation at the Cα—Cβ bond. The carbonyl fragment displays pronounced asymmetry at the exo-cyclic angles, being N12—C13—O14 and O14—C13—O15 of 128.4 (1)° and 121.9 (1)°, respectively, because of both electronic and steric factors due to the presence of different atoms bound to C13 (Grassi et al., 2001). The dimensions within the benzimidazole and the oxazolidine moieties are in excellent agreement with those found in the benzimidazole and oxazolidine crystal structures (Totsatitpaisan et al., 2008; Wouters et al., 1997).

Packing analysis of the crystal lattice indicates that the tridimensional molecular arrangement is ruled by many H-bonding interactions. A strong H-bond N1—H1···N8 gives rise to a molecular chain [C(4)] along the c axis (Figure 4). Another H-bonding interaction C11—H11···O14 generates a chain [C(5)] along the a axis, perpendicular to the previous one.

Experimental

A solution of dibromoethane (3 mmol, 0.258 ml) in ethyl acetate (2 ml) was added over 10 minutes to a stirred mixture of 2-(2-aminoethyl)-benzimidazole dihydrochloride (1 mmol, 0.234 g), potassium carbonate (10 mmol, 1.38 g), ethyl acetate (5 ml) and water (2 ml). After the reaction mixture was refluxed for 36 h, the two phases were separated and the aqueous layer was extracted with ethyl acetate (2 x 5 ml). The combined organic phases were dried over anhydrous Na₂SO₄, filtered and concentrated. Elution with a mixture of chloroform and methanol (99:1) gave the title molecule as colourless crystals (yield: 30%). ¹H-NMR (CDCl₃, 300 MHz) δ 3.30 (t, J = 6.59, 2H, CH₂), 3.61 (t, J = 6.71, 2H, CH₂), 3.83 (t, J = 6.59, 2H, CH₂), 4.28–4.34 (t, J = 6.71, 2H, CH₂), 7.22–7.25 (m, 4H, Ar), 7.56 (bs, 1H, NH).