Study On The Synthesis Of Difenoconazole And Intermediate Compounds

In this paper, the synthesis of the difenoconazole was studied.2,4-dichloroacetophenone was prepared from m-dichlorobenzene and acetyl chloride through Friedel-Crafts acylation. Reaction of2,4-dichloroacetophenone with p-Chlorophenol in toluene, gave intermediate4-(4-chlorophenoxy)-2-chloroacetophenone. α-Bromination of the intermediate4-(4-chlorophenoxy)-2-Chloroacetophenone with bromine, followed by condensation with1,2-propanediol and1H-1,2,4-triazole gave the final product difenoconazole. In the Friedel-Crafts acylation reaction,[Bmim]Cl-FeCl3instead of AICl3was used as catalyst and2,4-dichloro-acetophenone was obtained in96.6%yield. In the reaction of2,4-dichloroacetophenone with p-Chlorophenol, toluene instead of DMF was used as solvent and the reaction was carried out in much lower temperature compared with the liturature method. These improvements made the work up process simpler and the whole process greener.In this paper, a new synthetic route of difenoconazole was also reported.2,2’,4’-Trichloroacetophenone was prepared from1,3-dichlorobenzene and2-chloroacetyl chloride via Friedel-Crafts acylation in ionic liquid [Bmim]Cl-FeCl3. Cyclization of the intermediate2,2’,4’-trichloroacetophenone with1,2-propanediol, followed by condensation with lH-l,2,4-triazole and p-Chlorophenol gave the final product difenoconazole. The new route was a four-step reaction, compared with the original5steps reaction. Through process optimization, the yields of four steps were94.1%、96.3%、63.7%and93.3%, respectively. The overall yield of difenoconazole was53.9%.The direct introduction of the α-chorine atom avoided the bromination step. Use of ionic liquid [Bmim]Cl-FeCl3in the Friedel-Crafts reaction eliminates the use of AICl3, which is difficult to recover. Therefore, the cost and pollution were remarkably reduced.