4-Fluoro-3-nitrobenzoic acid

• as starting reagent in the preparation of novel benzimidazoles having antimycobacterial activity
• in preparation of series of novel acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors containing benzimidazole core structure
• in preparation of bis(heterocyclic) skeletal precursors for the Pictet-Spengler reaction
• in solid-phase synthesis of trisubstituted [1,3,5]triazino[1,2-a]benzimidazole-2,4(3H,10H)-diones

456-22-4

453-71-4

General procedure for the synthesis of 4-fluoro-3-nitrobenzoic acid from 4-fluorobenzoic acid: Potassium nitrate (39.7 g, 0.39 mol, 1.1 eq.) was added in batches to a solution of 4-fluorobenzoic acid (50.0 g, 0.36 mol, 1.0 eq.) dissolved in concentrated sulphuric acid (180 ml) under cooling in an ice bath. The reaction mixture was stirred overnight at room temperature and then slowly poured over crushed ice (800 g) under continuous stirring. The resulting mixture was allowed to stand at room temperature overnight, followed by filtration and washing of the solid product with plenty of water. Finally, treatment by azeotropic drying with toluene afforded 59.5 g (90% yield) of 4-fluoro-3-nitrobenzoic acid as a light yellow solid.1H NMR (400 MHz, DMSO-d6): δ 7.69-7.74 (m, 1H), 8.29-8.32 (m, 1H), 8.56 (d, J=7.2 Hz, 1H), 13.75 ( br s, 1H).