Study On Rhodium (Ⅲ) Catalytic Synthesis Of Flavonoids And Improvement Of The Synthesis Of Finafloxacin Intermediates

The research work in this paper includes the rhodium-catalyzed synthesis of Flavonoids from salicylaldehyde and oxythio-Yelide and the improvement and optimization of the synthesis of 2,4-dichloro-3-cyano-5-fluorobenzoic acid,an important intermediate of quinolone antibiotic finafloxacin.（1）Flavonoids,as a kind of important bioactive substances,have many pharmacological effects,such as anti-inflammatory,anti-tumor,anti-virus,anti-oxidation and so on.One of the important sources of flavonoids is artificial synthesis.So far,many synthetic methods of flavonoid derivatives have been reported.In this paper,we first describe the synthesis of flavonoids by the reaction of Salicylaldehyde and oxysulfur Yelide catalyzed by rhodium.The scheme uses[Cp*Rh Cl₂]₂ as catalyst,Cs OAc as additive,H₂SO₄/HOAc as dehydrating agent,and one-pot method to effectively obtain flavonoids.The optimum reaction conditions were obtained by screening the additives,reaction temperature and time.The experiment expanded 28 substrates,and the experimental data were consistent with the reports.The highest yield was 95%.This scheme provides a new synthetic scheme of flavonoids,which is characterized by salicylaldehyde as the initial substrate,cheap and easy to obtain.Oxysulfur Yelide takes the place of diazo compound as the precursor of carbene to participate in the reaction,providing a safer and stable reaction environment,and has good reactivity,wide substrate adaptability and high yield.It has a certain extent in the application of carbene precursors in drug synthesis.Theoretical guidance.（2）Since the discovery of quinolones,their synthesis has been the focus of research.Finafloxacin,as a new quinolone drug,is used in the treatment of acute otitis externa.2,4-dichloro-3-cyano-5-fluorobenzoic acid is an important intermediate in the synthesis of phenafloxacin.In this paper,the synthesis method of 2,4-dichloro-3-cyano-5-fluorobenzoic acid was improved and optimized.Firstly,2,4-dichloro-3-fluoroacetophenone was synthesized from 2,6-dichloro-3-fluoroacetophenone by oxidation to carboxylic acid,aminolysis,dehydration,Bromination and carboxylic acidification.The process of aminolysis and final carboxylic acidification was optimized.Secondly,trichloroisocyanuric acid was used as chlorinating reagent to produce alpha,alpha,2,4-pentachloro-3-fluoroacetophenone in 96%yield.Aminolysis in ammonia water is benzamide.Sodium hypochlorite can effectively oxidize acetophenone to benzoic acid in 58%yield,and then form benzamide structure through aminolysis.The synthesis of 2,4-dichloro-3-cyano-5-fluorobenzoic acid was completed by Grignard exchange and carboxylic acidification of 3-bromo-2,6-dichloro-5-fluorobenzonitrile.The conversion of isopropyl magnesium chloride and lithium chloride complex was effectively improved,and the yield was increased from 60%to 89%.In this scheme,trichloroisocyanuric acid replaces chlorine gas as chlorination reagent,which improves the safety of industrial production.The use of the complex of isopropyl magnesium chloride and lithium chloride has greatly improved the yield and increased the benefit of industrial production.