Synthesis Of Diphenyl Derivates

Aromatic diazonium salts, which are easily pepared, have widely been used for manyyears. They are both useful and attractive partners represent an alternative to aryl triflatesor halides. Compared with other electrophilic reagents, aromatic diazonium salts havemany advantages, such as easy availability from anilines, superior reactivity andenvironmentally friendly. So far, aromatic diazonium salts have been applied in a series ofcoupling reactions, for example Mizoroki–Heck reactions, Suzuki–Miyaura and Stillecross coupling reactions.4-bromo-2-fluorobiphenyl is raw material for synthesizing special functionalfluorochemicals and the intermediate for new drugs, such as flurbiprofen, which isnon-steroidal anti-fever drug. Some synthetic methods of4-bromo-2-fluorobiphenyl areintroduced, compared and optimized. And finally we established an applicant syntheticroute: taking2-fluoroaniline as starting material,4-bromo-2-fluoroaniline is obtainedthrough NBS-bromination at0-5℃. Isopropyl nitrite is received by the reaction ofisopropanol sodium nitrite and hydrochloric acid in water at0-5℃. Diazonium salt can besynthesized by4-bromo-2-fluoroaniline and isopropyl nitrite, and then reacts withbenzene catalyzed by CuCl to compose4-bromo-2-fluorobiphenyl. The yield of thisreaction is59.8%. Based on this reaction, a variety of aniline derivatives as substrateshave been used in the coupling reaction. When the ratio of aniline derivatives andisopropyl sodium is1:3, the yield of the coupling reaction, which is catalyzed by CuCland kept for1.5h, is more than60%. This result is very satisfying.We take a future study of coupling reactions in which alkyl nitrites are used asdiazotization reagents and cuprous ion is applied as catalyst. It is clarified When the ratioof aniline derivatives and isopropyl sodium is1:3and reaction is catalyzed by Cu+andkept for1.5h, the yield of this reaction is better. We found that there are many advantagesusing diazonium salts synthesized by alkyl nitrites to react with benzene, such as easyoperations, mild conditions and short reaction time. Based on the experiments, we foundoptimum reaction conditions. A new and effective synthetic route has been established forcomposing biphenyls.