Research On Optimized Synthesis Of Herbicide Pinoxaden

Pinoxaden is an acetyl-Co A carboxylase?ACC?inhibitor herbicide developed by Syngenta Crop Protection Ltd.It is mainly used to control annual grass weeds in wheat fields after germination,such as clubhead,hard grass,foxtail,ryegrass,and maidenhair.Because its special phenylpyrazoline structure is considered as a new herbicidal target,its development solves the resistance of weeds to AOPP herbicides in recent decades.At the same time,Pinoxaden can be used in combination with a safener,such as triacetate,to enhance the stability of the herbicidal effect.At present,there are two mainstream products of Pinoxaden:Aixiu?50 g/L Pinoxaden?and Danone?50 g/L Pinoxaden and Clodinafop-propargyl?.In 2015,Pinoxaden was ranked second in the list of the top ten herbicides in global cereal farms.Due to its good selectivity,high weed control rate for grasses,wide weed control spectrum,low soil activity,and no impact on subsequent crops,Pinoxaden is promoting into a tough weapon for woody weed control in modern agricultural.The synthetic route designed focuses on the synthesis of dimethyl?2,6-diethyl-4-methylphenyl?malonate.2,6-diethyl-4-methylaniline was used as starting material when the key intermediate?2,6-diethyl-4-methylphenyl?malonate needs to be prepared.The diazonium salt was produced with sodium nitrite and hydrobromic acid.Cu Br was added in a one-pot method,and Sandmeyer reaction was used to acquire 2,6-diethyl-4-methyl bromobenzene with a yield in 86.4%.To gain?2,6-diethyl-4-methylphenyl?malononitrile?PPh₃?₂Pd Cl₂ was appleed as the palladium catalyst,and 2,6-diethyl-4-methylbromo-benzene and malononitrile were used as substrates.Then the Pinner reaction occurred in a40%solution of concentrated sulfuric acid in methanol.?2,6-diethyl-4-methylphenyl?malononitrile was hydrolyzed to obtain the key intermediate?2,6-diethyl-4-Methylphenyl?dimethyl malonate,the yield at this step was 74.1%.To obtain intermediate 8-?2,6-diethyl-4-methylbenzene?tetrahydropyrazole[1,2-d][1,4,5]-oxadiazepine-7,9-dione,using oxadiazepine hydrogen bromide as nucleophile,triethylamine catalyzed,high temperature amidation of dimethyl?2,6-diethyl-4-methylphenyl?malonate.The yield was78.1%.Finally,under the action of DMAP as catalysis and triethylamine as acid binding,pivaloyl chloride was appleed in the acylating agent,8-?2,6-diethyl-4-methylbenzene?tetrahydropyrazole[1,2-d][1,4,5]-oxadiazepine-7,9-dione changed into the target product,Pinoxaden,by acetylation with a single-step yield of 82.1%.The route designed used 2,6-diethyl-4-methylaniline,malononitrile,oxadiazepine hydrobromide and pivaloyl chloride as raw materials.Totally,5 steps were included to obtain the target product Pinoxaden,with a yield of 35%.The HPLC purity was 99.92%,which was greater than the 23%yield and 98.1%purity reported in the literature.Based on relevant reports and literature research,this thesis designed and optimized the synthesis route of the herbicide Pinoxaden in view of the defects existing in the current synthesis route.At the same time,the unit mechanism involved in the route was discussed and analyzed,and the optimal reaction conditions were screened.There are some factors that are not conducive to scale-up have been solved,such as lengthy reaction steps,low yields,using highly toxic or organometallic compounds,high equipment requirements,cumbersome operations,low principle utilization,or the need for special catalytic ligands.The new route makes the synthesis of Pinoxaden fulfil the environmental requirements about‘green chemistry',and has certain potential for scale-up production.