Study On The Copper-Catalyzed Replacement Of Bromine By Fluorine And Chlorine In Aromatic Compounds

Aryl fluorides and aryl chlorides, used as highly useful chemical intermediates, are widely used to synthesize pharmaceuticals, agrochemicals and functional materials. Especially, radioactive 18F-labeled organic compounds are also widely used as contrast agents for positron emission tomography (PET). However, traditional methods for the introduction of a fluorine atom into an aromatic framework usually require harsh conditions that are incompatible with many functional groups. Classic methods for the synthesis of chlorinated arenes suffer from poor selectivity, low efficiency for electron-deficient substracts and inconvenient operation.In this paper, a further exploration and research on the replacement of bromine by fluorine and chlorine in aromatic compounds was conducted with cheap and environmentally friendly copper as a catalyst. And, a facile and efficient replacement of bromine by chlorine in aromatic compounds was achieved.1. We examined the effect of fluorine sourices, catalysts, ligands, solvents and phase transfer catalysts on the replacement of bromine by fluorine in 4-bromoacetophenone. But it was failed to achieve the smooth progress of fluoridation. We speculated that the ligand didn't meet the demand of reductive elimination of the Ar-F bond.2. Using CU2O as a catalyst and L-proline as a ligand, replacement of bromine by chlorine in 4-bromotoluene with tetramethylammonium chloride occurred at 110℃for 20 h to afford 4-chlorotoluene in 98% yield. Under the same conditions described above, aromatic compounds including heterocyclic and polycyclic aromatic compounds could be effectively converted into corresponding chloro aromatic compounds in 81-99% yield.3. We have described the first copper-catalyzed replacement of bromine by chlorine in aromatic compounds. This protocol offers several advantages over previous methods. The conditions are mild and the catalytic system is environmentally friendly. This reaction has broad substrate scope and excellent functional group tolerance. It's highly complementary to traditional methods for the synthesis of chlorinated arenes.