General Papers ARKIVOC 2007 (xvi) 73-82
reaction of 8 with o-fluorophenol and p-fluorophenol was performed in the presence of K2CO3 in DMSO at 100–120 °C10a affording the fluorophenyl benzimidazole (heteroaryl) ethers 10a–10b, which on hydrogenation gave the desired compounds 2a–2b, respectively in good yields.
Preparation of the model compounds 3 and 4 required different phenolic coupling conditions. Coupling of commercially available 2-chloronitrobenzene 11 with the potassium salt of ofluorophenol at 110–120 °C5b yielded the fluorophenylaryl ether compound 12a which on Pd-C catalyzed hydrogenation gave 3a. The compound 4a was prepared from NaH based coupling14 of 1315 with o-fluorophenol to afford the fluorophenyl phenyl pyridyl (heteroaryl) ether 14a with subsequent Pd/C catalyzed hydrogenation. p-Fluorinated compounds 3b and 4b were prepared in similar sequences from 12 and 14, respectively in good yields (Scheme 2).
o-fluorophenol or p-fluorophenol
12a X = F, Y = H (63%) 12b X = H, Y = F (98%)
O X NO2 3a (87%) 3b (100%) NO2 Cl Y KOH, 110 0C, 30 min then 120 0C, 2 h H2, Pd-C MeOH, r.t. Overnight o-fluorophenol or p-fluorophenol X NO2
F
H2, Pd-C
O
NaH, THF
N
4a (59%) MeOH, r.t. 4b (96%)
N NO2 r.t., 2 h Y
12 h
13 14a X = F, Y = H (61%) 14b X = H, Y = F (39%) Scheme 2
In summary, we have demonstrated the detailed syntheses of some novel fluorophenylaryl / heteroaryl ether derivatives which are structurally similar to some potent anti-inflammatory agents like Flosulide. The synthetic procedures are more straightforward and convenient than the traditional multi-step syntheses. These synthetic studies are expected to be helpful to generate some highly potent compounds of similar biological activities. The biological activity studies of the synthesized compounds are in progress.
Experimental Section
General Procedures. All melting points were determined with a Yanagimoto Micro Melting Point apparatus and are uncorrected. IR spectra (cm-1) were recorded on a Perkin-Elmer 1600 spectrometer. 1H-NMR spectra were measured as solutions in CDCl3, CD3OD, D2O or DMSO-d6
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