Optimized Synthesis Of Saflufenacil

Saflufenacil is a inhibiting protoporphyrinogen inhibitor herbicide developed by BASF Company.It is mainly used for the control of broadleaf weeds,which can effectively control more than 90 kinds of weeds,including resistant weeds.Due to its unique mechanism of action,related resistant weeds have evolved slowly.At the same time,saflufenacil and other herbicides can be used in combination to reduce amounts of herbicides and increase the efficiency.In 2010,saflufenacil was marketed in China as 70% water dispersible granule.Based on the related research results from literatures and reports,the synthetic process of the key intermediate N-Methyl-N-isopropyl aminosulfonamide and saflufenacil are designed and optimized in this thesis in order to reduce the existing problems.The reaction conditions of each step in the route are also explored and optimized to make the process greener,environment-friendly,and suitable for industrial production.Design of the synthesis methods for N-Methyl-N-isopropyl aminosulfonamide and construction of uracil ring are the key work of this paper.Firstly,N-Methyl-N-isopropyl aminosulfonamide was synthesized,using chlorosulfonyl isocyanate as raw material,through the reaction with t-butanol to form t-butoxycarbonyl group to achieve the purpose of amino protection.Then,it is condensed with N-methylpropan-2-amine using triethylamine as acid-binding agent to obtain the intermediate t-butyl(N-isopropyl-Nmethylsulfonyl)carbamate.The Boc group was removed by HCl/ethanol to obtain N-methylN-isopropyl Sulfamide in 74.8% yield over three steps.Secondly,adopting 2-chloro-4-fluorobenzoic acid as raw material,the intermediate 2-chloro-4-fluoro-5-nitrobenzoyl chloride was obtained by nitration of nitric acid and acylation of thionyl chloride.2-chloro-4-fluoro-5-nitrobenzoyl chloride and N-methyl-N-isopropyl Sulfamide were subjected to condensation reaction using triethylamine as acid-binding agent to give the intermediate 2-chloro-4-fluoro-N-(N-isopropyl-N-sulfonyl)-5-nitrobenzamide.2-chloro-4-fluoro-N-(Nisopropyl-N-sulfonyl)-5-nitrobenzamide was reduced by Pd/C through catalytic hydrogenation,condensed with methyl chloroformate to give methyl(4-chloro-2-fluoro-5-((N-isopropyl-N-methylsulfamoyl)carbamoyl)phenyl)carbamate.Then the intermediate 2-chloro-5-(2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl)-4-fluoro-N-(Nisopropyl-N-methylsulfamoyl)benzamide was obtained through twice ester aminolysis reactions with 3-amino-4,4,4-trifluorocrotonic acid ethyl ester in 78% yield.Finally,methylation of dimethyl sulfate gives the target product saflufenacil.The total yield of the route was 43.7%.Based on the related literatures and data,the synthesis mechanisms of each reactions are discussed and analyzed,and the reaction conditions are screened in this thesis.