Study On The Synthesis Of Tembotrione

Tembotrione,which was developed by Bayer Corporation as herbicide of triketone and HPPD inhibitor,is broadly applied in corn field to control the annual grass weed and broadleaf weed.The synthetic route and process optimization of tembotrione were studied in this thesis.On the basis of literature,the 3-chloro-2-methylaniline was determined as the starting material,the target compound tembotrione was synthesized through 10 steps of diazotization-methylsulfurization,Friedel-Crafts acylation,oxidation,haloform,esterification,free radical bromination,etherification,hydrolysis,acylation and condensation.In the paper,the conditions of diazotization-methylsulfurization,Friedel-Crafts acylation,oxidation,haloform,esterification and free radical bromination were optimized in the detail.The diazoid-methyl sulfide reaction avoids the problem of dimethyl sulfide that is common in other routes.NBS was selected as the bromination reagent to reduce the experimental risk and improve the safety of operation.The total yield was 7.6%and the HPLC purity of tembotrione was 99%.The chemical structure of tembotrione and its intermediates were characterized by ¹H-NMR,¹³C-NMR and LC-MS and so on.Three impurities was isolated in the process of synthesizing intermediate 1 by column chromatography,two of them were characterized as 3-chloro-2-methylphenol（1a）and（2,3’-dichloro-2’,3-dimethyl-[1,1’-biphenyl]-4-yl）（methyl）sulfane（1b）.1c was preliminarily presumed to be biphenyl diazo amino compound.The impurity（2a）of Friedel-Crafts acylation was separated by column chromatography and characterized as 1-（2,4-dichloro-3-methylphenyl）ethan-1-one.In the synthesis of intermediate 3,basing on the separation and identification of impurity（3a）as 3-chloro-2-methyl-4-methylsulfone acetophenone,the mechanism of oxidation was proved through two steps.The impurity（4a）was isolated in the process of synthesizing intermediate 4 by recrystallization and determined as 2-chloro-3-methyl-4-（methylsulfinyl）benzoic acid.The impurity（5a）was separated in the process of synthesizing intermediate 5 by recrystallization and characterized as methyl 2-chloro-3-methyl-4-（methylsulfinyl）benzoate.Their chemical structures were characterized by ¹H-NMR,¹³C-NMR,HSQC and LC-MS.