Paper
Crystal Structure of 1-Cyclopropyl-2-ethyl-5-fluoro-6-(4-methylpiperazin-1-yl)-1H-benzimidazole
Published Aug 1, 2001 · S. Özbey, C. Kuş, H. Göker
Analytical Sciences
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Abstract
biological activities,1 and some of them are used as drugs.2,3 In previous studies,4,5 we reported on the synthesis and biological evaluation of 1,2,5(6)-trisubstituted benzimidazoles as antihistaminic and antimicrobial agents. The synthesis of ethyl 1-cyclopropyl-5-fluoro-6-(4-methylpiperazine-1-yl)-1H-benzimidazole-2-acetate (1) was performed according to reported methods.6,7 1-Cyclopropyl-2-ethyl-5fluoro-6-(4-methylpiperazin-1-yl)-1H-benzimidazole (2) was prepared by the reduction of 1 with Pd/C in a hydrogen atmosphere (Scheme 1). A suspension of 1 (300 mg, 0.8 mmol) in N,N-dimethylformamide (0.5 mL) was hydrogenated over 10% Pd/C. After dilution with ethylacetate and filtration, the solution was extracted with water and 10% aqueous NaCl solution. The organic layer was dried and evaporated. The residue was purified by column chromatography (CHCl3) and recrystallized from isopropanol, yielding 160 mg of 2. Its structure was assigned by NMR as well as mass and elemental analysis results. The X-ray structure was determined in order to establish the conformation of the molecule. The crystal and experimental details are summarized in Table 1. The reflection data were collected at 23 ̊C using the ω–2θ scan technique by using graphite-monochromated Mo Kα radiation (λ = 0.71069 Å). A colorless prismatic crystal of 2 with approximate dimensions of 0.24 × 0.16 × 0.60 mm was used for all x-ray experiments. A total of 1933 reflections were measured, 1920 of which were unique. During data collections three intensity control reflections were monitored every 2 h, showing no loss of intensity. The structure was solved by direct methods with SIR928 and refined by a full-matrix least-squares method using anisotropic displacement parameters for all nonhydrogen atoms. Hydrogen atoms were placed geometrically 0.95 Å from their parent atoms. For all hydrogen atoms, a riding model was used and displacement parameters were fixed at 1.3Ueq of the parent atoms. The final atomic parameters and the molecular geometry for the non-hydrogen atoms are given in Tables 2 and 3, respectively. An ORTEP drawing of the compound with atom numbering is shown in Fig. 1. The structure predicted from chemical and spectral analysis has been confirmed by an x-ray crystallographic analysis. The bond lengths and angles agree with the mean values reported for those analogues compounds. As expected, the benzimidazole ring system is nearly planar. The geometry observed for the piperazine ring shows no significant distortion from a perfect chair. The perpendicular distances of the N2 and N4 atoms from the best plane defined by atoms C15, C16, C17, C18 are –0.671(2) and 0.666(3)Å, respectively. In terms of the ringpuckering coordinates, the amplitudes and phase magnitudes9 are Q = 0.581 Å, φ = 101.2 and θ = 179.2 ̊. The dihedral angles between the best planes of the benzimidazole and piperazine ring, benzimidazole and cyclopropyl ring are 136.1(1) and 1019 ANALYTICAL SCIENCES AUGUST 2001, VOL. 17 2001 © The Japan Society for Analytical Chemistry
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