Diclosulam Process Development

Diclosulfonamide is a sulfonamide herbicide,developed by Dow,Agroscience.It is a acetyllactic acid synthase(Als)inhibitor,which can be rapidly absorbed by the roots,stems and leaves of weeds and can be applied to peanut,soybean field seedling and soil treatment before planting.It has a good effect on the prevention of broadleaf weeds.Its main characteristic is low dosage,safe to crop wait,and with wide market application.This thesis focused on the optimization of a reasonable process production route according to the research and the small-scale synthetic route.Dichlorosulfonylamine was obtained from 2-methiony-4,6-difluorouracil by hydrazine hydration,oxidation,benzyl protection,ethoxy substitution,chlorination and condensation reaction.This thesis focused on studying the factors of each step in detail,including specifications of reactive materials,reaction system status,addition time,the choice of solvent,washing operation,drying of intermediates,refining method etc.Finally,an optimized process route was obtained with mild conditions,stable parameters and easy operation,and the purity of final product can reach to 99.5%.We combined the first two steps to a continuous production process,and monitoring compounds 2.The synthesis of compounds 3,compounds 4,compounds 5 and compound 6 was treated as unit reactions,monitoring all intermediates.Compound 6 is refined to afford the qualified product.After the small-scale test and the optimization,we carry on the kilogram scale-up experiment and the comparision of parameters is confirmed after the scaleup of the feeding quantity.After the comparison with the result of the small-scale test,finally a feasible industrial production route is established.Combining with the experimental data of small scale test and kilogram,the process operation steps were optimized.After the preparation of each step of the reaction procedure and the statistics of the individual consumption data of each step,a consumption list of materials for the production of one ton of finished products was established.According to the operating rules,the block flow diagrams of each step were drew.Based on the optimized operation parameters,the production cycle of each unit reaction is calculated to estimate the time needed for a batch of finished products.According to the feed rate,yield and volume of the reactor,the volume of each reaction kettle were calculated to avoid the bottleneck caused by the unit production cycle or the size of the reactor,thus restricting the production capacity.After a large number of experimental parameters optimization and operation details improvement,the production operation procedures were formulated,and the material consumption,unit consumption and reactor volume were obtained,providing a more reliable data support for industrial production.In the process of experimental optimization,the structure of each intermediate and final product was confirmed by carbon and hydrogen NMR spectra to avoid deviation in the process of parameter optimization.