Preparation Of Fullerene Pd Nanocatalyst And Its Application In The Synthesis Of Biphenyl Drugs

Palladium catalyzed Suzuki coupling reaction has been one of the most effective and important methods for biphenyl drugs synthesis since it was reported in Suzuki in 1979.In this paper,a water soluble fullerene Pd nanocatalyst was synthesized to catalyze the coupling reaction of halogenated aromatics and arylboronic acid to synthetize biphenyl compounds,and used in the synthesis process of antihypertensive drugs,and other non steroidal anti-inflammatory drugs,such as 2-Cyano-4'-methylbiphenyl,Biphenyl acetic acide and Diflunisal,which are important intermediate for antihypertensive drugs.The research content of this paper is divided into four parts:?1?A water-soluble fullerene nanoparticle C₆₀-TEGs is assembled as a carrier to coordinate with two palladium chloride,and the[O,O]on tetraethylene glycol is used to form a pentacyclic structure with the ligand of[O,O]and metal palladium,and the oxygen atom has a soliton pair.It has a strong coordination ability and can realize the coordination bond load of the two palladium chloride.A new type of catalyst is labeled C₆₀-TEGs/PdCl₂.The Suzuki reaction of 4-Bromophenylaceton with phenylboronic acid as a model reaction optimized the optimum reaction conditions.The experimental results show that 98.0%of the isolated yield can be obtained when the amount of catalyst is 0.01 mol%C₆₀-TEGs/PdCl₂,the potassium carbonate is the base,the deionized water is the solvent,and the air is reacted at room temperature for 4 h.The catalyst can be recovered by simple extraction.After repeated use of 5 times,the catalytic efficiency has not decreased significantly.Under the optimal experimental conditions,we synthesized a series of biphenyl compounds.?2?With 2-bromobenzonitrile and 4-methylphenylboronic acid as the raw material and deionized water as solvent,the C₆₀-TEGs/PdCl₂ in situ catalytic system reacted at room temperature 4 h to catalyze the Suzuki coupling reaction to synthesize the key intermediate of the angiotensin II receptor antagonist,2-Cyano-4'-methylbiphenyl,with a isolated yield of 93.6%and a purity of 98.27%?HPLC?.?3?With 4-bromophenylacetic acid and phenylboronic acid as raw material,0.01mol%C₆₀-TEGs/PdCl₂ as catalyst,deionized water as solvent,potassium carbonate as base,and catalyzed Suzuki coupling reaction at room temperature conditions,4 h can one step synthesis of Biphenyl acetic acide.The product with purity of 99.92%?HPLC?can be obtained by simple post-processing,and the yield is as high as 94.7%.?4?Using 5-bromosalicylic and 2,4-difluorophenylboronicaid as raw material and 0.1mol%Pd catalyst,the NSAIDs Diflunisal were successfully prepared by Suzuki coupling step by step.The final yield was 90.0%and the purity was 98.04%?HPLC?.