Crystal structure of 2-{[1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl­oxy]carbon­yl}benzoic acid

Hafiz Abdullah Shahid; Sajid Jahangir; Syed Adnan Ali Shah; Hamizah Mohd Zaki; Humera Naz

doi:10.1107/S1600536814023927

. 2014 Nov 5;70(Pt 12):o1237–o1238. doi: 10.1107/S1600536814023927

Crystal structure of 2-{[1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yloxy]carbonyl}benzoic acid

Hafiz Abdullah Shahid ^a, Sajid Jahangir ^a, Syed Adnan Ali Shah ^b,^c, Hamizah Mohd Zaki ^b,^d, Humera Naz ^b,^c,^*

PMCID: PMC4257427 PMID: 25553019

Abstract

In the title compound, C₁₅H₁₅N₃O₆, the dihedral angle between the planes of the benzene and imidazole rings is 34.93 (10)°. An intramolecular C—H⋯O hydrogen bond is observed. In the crystal, O—H⋯N hydrogen bonds link the molecules into chains parallel to the c axis.

Keywords: crystal structure, nitroimidazoles, O—H⋯N hydrogen bonds, pharmaceuticals

Related literature

For the applications and biological activities of nitroimidazole and its derivatives, see: Maeda et al. (1953 ▶); Larina & Lopyrev (2009 ▶); Zhang et al. (2014 ▶); Gillis & Wiseman (1996 ▶). For the crystal structure of related compounds, see: Xiao et al. (2008 ▶); Shahid et al. (2014 ▶).

Experimental

Crystal data

C₁₅H₁₅N₃O₆
M _r = 333.30
Monoclinic,
a = 11.189 (3) Å
b = 6.9489 (17) Å
c = 19.979 (5) Å
β = 98.056 (10)°
V = 1538.0 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 296 K
0.50 × 0.50 × 0.38 mm

Data collection

Bruker SMART APEX CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2000 ▶) T _min = 0.946, T _max = 0.958
20047 measured reflections
2865 independent reflections
2515 reflections with I > 2σ(I)
R _int = 0.082

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.119
S = 1.07
2865 reflections
222 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.31 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Data collection: SMART (Bruker, 2000 ▶); cell refinement: SAINT (Bruker, 2000 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick 2008 ▶); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL, PARST (Nardelli, 1995 ▶) and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536814023927/rz5138sup1.cif

e-70-o1237-sup1.cif^{(716.4KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814023927/rz5138Isup2.hkl

e-70-o1237-Isup2.hkl^{(157.4KB, hkl)}

Click here for additional data file.^{(6.2KB, cml)}

Supporting information file. DOI: 10.1107/S1600536814023927/rz5138Isup3.cml

Click here for additional data file.^{(1.2MB, tif)}

. DOI: 10.1107/S1600536814023927/rz5138fig1.tif

The molecular structure of the title compound with displacement ellipsoids drawn at 50% probability level.

Click here for additional data file.^{(1.3MB, tif)}

b . DOI: 10.1107/S1600536814023927/rz5138fig2.tif

Crystal packing of the title compound viewed down the b axis. Only hydrogen atoms involved in O—H⋯N hydrogen bonds (dashed lines) are shown.

CCDC reference: 1031694

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (, ).

DHA	DH	HA	D A	DHA
C9H9AO5	0.98	2.53	3.115(3)	118
O1H1DN1ⁱ	0.96(3)	1.78(3)	2.730(2)	175(3)

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors would like to acknowledge Nabiqasim Pharmaceutical Industries (PVT) Ltd for the financial support during the research work. HAS is grateful to Nasir Ahmed Shamsi MD for moral support and SAAS would like to acknowledge the Ministry of Higher Education (MOHE) for financial support under the Fundamental Research Grant Scheme (FRGS) with reference numbers 600-RMI/FRGS 5/3 (12/2012).

supplementary crystallographic information

S1. Comment

Nitroimidazoles are well recognized as antibacterial agents since the early 1950s as azomycin, i.e. 2-nitroimidazole, was discovered (Maeda et al., 1953). The imidazole moiety has a wide range of biological activities such as anticancer, antifungal, antibacterial, antitubercular, antiparasitic, antihistaminic, antineuropathic, antihypertensive, anti-inflammatory, antiobesity, antiviral, antitumor, antihelmintic, antiallergic, antineoplastic, local analgesic, and spazmolytic activities (Larina & Lopyrev, 2009; Zhang et al., 2014). Nowadays, various drugs are available which belongs to the nitroimidazole class such as secnidazole (Flagentyl), metronidazole (Flagyl), ornidazole (Xynor), tinidazole (Fasigyn) and others. Secnidazole is an efficient drug in the treatment of protozoal infections. Secnidazole has been explored for the treatment of amoebiasis, giardiasis, urogenital trichomoniasis and nonspecific bacterial vaginosis (Gillis & Wiseman, 1996).

In the title compound (Fig. 1), the mean planes through the benzene (C2–C7) and imidazole (N2/C11/N1/C12/C13) rings form a dihedral angle of 34.93 (10)°. The bond lengths and angles are within the normal ranges and in agreement with those observed in related compounds (Xiao et al., 2008; Shahid et al.; 2014). The molecular conformation is stabilized by a non-classical C—H···O hydrogen bond (Table 1). In the crystal, molecules are linked into chains parallel to the c axis via intermolecular O—H···N hydrogen bonds (Table 1, Fig. 2).

S2. Experimental

For the synthesis of title compound, 10.8 mmol of secnidazole (2 g) and 10.8 mmol of phthalic anhydride (1.6 g) were dissolved in a mixture of acetone (15 ml) and pyridine (1 ml). The reaction mixture was allowed to reflux for 12 h. After completion of the reaction, the solvent was evaporated under vacuum and the crude product was washed with little amounts of pure water, methanol and toluene to get colourless crystals in 63% yield. M. p.: 461-463 K. ¹H NMR (500 MHz, DMSO-d6): δ 8.044 (s, 1 H, imidazole H), 7.782–7.756 (m, 1 H, Ar H), 7.639–7.595 (m, 2 H, ArH), 7.295–7.263 (m, 1 H, Ar H), 5.397–5.334 (m, 1 H, CH), 4.650–4.421 (m, 2 H, CH₂), 2.320 (s, 3 H, CH₃), 1.392–1.379 (d, J=6.5 Hz, 3 H, CH₃). ¹³C NMR (125 MHz, DMSO-d6): δ 167.93 (C—O), 167.60 (C—O), 152.08 (C—N), 139.02 (C—NO₂), 133.65 (imidazole CH), 132.81, 132.03, 131.72, 131.52, 129.57, 127.83 (aromatic C), 70.70 (O—CH), 49.85 (N—CH₂), 17.09 and 14.40 (CH₃).