Technical Study On Preparation Of Felbinac Under Microwave Radiation

According to various synthesis methods of felbinac and its derivatives that had been published at home and abroad, first 1-biphenyl-4-yl-ethanone was synthesized via Friedel-Crafts acylation reaction, then 2-biphenyl-4-yl-1-morpholin-4-yl-ethanethione was synthesized via Willgerodt-Kindler reaction under microwave radiation using 1-biphenyl-4-yl-ethanone as raw, finally via saponification and acidification biphenyl-4-yl-acetic acid was obtained.As the dosage of catalyst, reaction temperature, reaction time and reagent mole ratio respectively increased, the yield of product firstly uprised and then lowered. Simultaneously, as the dosage of the solvent increased, the yield of product firstly uprised and then leveled off. When the mole ratio(catalyst : biphenyl)was 1.1~2.0, the reaction temperature was-11℃~ 15℃, reaction time was 0.5 h~2.5 h, the mole ratio(acetyl chloride : biphenyl)was 0.8~1.4, and the dosage of the solvent was 15 mL~50 mL, the yield of 1-biphenyl-4-yl-ethanone was 17%~ 98%. By the orthogonal experiment result ,we found that the optimum reaction condition was the mole ratio (catalyst : biphenyl) 1.6, the reaction temperature 5℃, reaction time 2.2 h, the mole ratio (acetyl chloride : biphenyl) 1.1.Then the yield of 1-biphenyl-4-yl-ethanone was 99.23% .As the microwave radiation power and reagent mole ratio respectively increased, the yield of 2-biphenyl-4-yl-1-morpholin-4-ethanethione firstly uprised and then lowered. But as the reaction time extended, the yield of the product firstly uprised and then leveled off. When the microwave power was 100 W~1200 W, the mole ratio (sulfur : 1-biphenyl-4-yl-ethanone) was 0.8~4.3, the reaction time was 2 min~14 min and the mole ratio (morpholine : 1-biphenyl-4-yl- ethanone) was 0.8~4.8, the yield of 2-biphenyl-4-yl-1-morpholin-4-ethanethione was 12%~65%. By the orthogonal experiment ,we found that the optimum reaction condition was reaction time 7 min, microwave power 950 W, the reagents mole ratio (1-biphenyl-4-yl-ethanone:sulfur : morpholine)1.0:3.5:1.5. Then the yield of 2-biphenyl-4-yl-1-morpholin-4-ethanethione was 66.20%.The hydrolysis condition was 70% (v/v) ethanol 15 mL, 50% (m/m) NaOH 3.5 mL, refluxing 2 hours. Filtering and filtrate vacuum distillate to remove solvent. Then adding some water and using diluted hydrochloric acidified to pH=2,we will get rough product, using acetic acid-water (1:1) re-crystallization and getting pure biphenyl-4-yl-acetic acid, the yield of biphenyl-4-yl-acetic acid was 80%.