Synthetic Technology Study Of Emamectin Benzoate

4"-deoxy-4"-epi-(methylamino)-avermectinB1benzoate(whose short name isemamectin benzoate), developed and marketed by Novartis Company, is anefficient、low toxic ity、low residue、eco-friendly and novel biological pesticides.Since it is on the market, its scale is increasing year by year, and it has a brightmarket prospect. Because of the complex synthesis processes and high cost, thesynthetic technology of emamectin benzoate has always been the hot topic ofpesticide production field.On the basis of traditional synthesis routes, this paper designs and comes upwith a new synthesis route of emamectin benzoate, which is short、low cost andmore suitable for industrialization. The concrete research contents and results areas follows:1. This new designed synthesis route of emamectin benzoate is started withavermactinB1a, after the C5-OH、C4"-OH selective oxidation reaction, C4"=Oselective amination reaction, C5=O、C4"=NCH3synchronous reduction reactionand C4"-NHCH3sality reaction four steps to get product emamectin benzoate.Compared with the traditional routes, the new one reduces two steps of protectionand deprotection.2. The synthesis of intermediate selective oxidation product: during theexperiments, dichloromethane was used as the solvent. The molar-ratio ofreaction is AVMB1a:DMSO:PDCP:TEMED=1:9:3:3.6, and react10min at thetempreture of-20~-15℃. HPLC was used to monitor the reaction, and measuredthat the purity of product is82.6%. And got a90.0%yield.3. During the experiments, take i-PrOAc as solvent, one-port was used tosynthese emamectin benzoate, which includes selective amination、synchronous reduction、sality with benzoic acid three steps.During the selective amination reaction, take heptamethyld is ila zane as themost suitable amination reagent, trifluoroacetic acid zinc salt as catalyst,molar-ratio is intermediate: amination reagent: catalyst=1:3:0.4, react1.5h atroom temperature, HPLC measured that the purity of selective amination productis47.4%.During the following synchronous reduction reaction, use NaBH4-EtOHreduction system, and the molar-ratio is intermediate: NaBH4=1:3, react60minat the temperature of-5~0℃, after some handles, got the i-PrOAc solution of4"-deoxy-4"-epi-(methylamino)-avermectinB1a.During the sality reaction, carboxybenzene was added directly at themolar-ratio is intermediate: carboxybenze ne=1:0.5, react30min at roomtemperature, HPLC measured that the purity of emamectin benzoate product is49.0%, the yield is62.0%.This paper takes four steps to synthese emamectin benzoate, eventually, got thepurity of product is49%, the total yield is55.8%, and the result is preferable.Compared with the traditional synthesis routes of emamectin benzoate, this routereduces the steps of protection and deprotection, simplifies the productionprocess, lower the cost, and has a better prospect of development.