Synthesis Process Improvement Of Flumiclorac-penty & Synthesis Of Thiophenes By Using β-ketothioamides

This paper includes two parts.The first part was the improvement of process route to synthesize flumiclorac-pentyl. Flumiclorac-pentyl(S-23031) was developed by Sumitomo Chemical in 1989 as a commercial product in the scope of protoporphyrinogen oxidase inhibitors herbicides, which was commonly applied to weeding in soybean, wheat and corn fields.In chapter one, the process route to the synthesis of grass herbicide flumiclorac-pentyl was modified by using 4-fluorophenol as the material through a seven-step reaction involving chlorination, acylation, nitrition, hydrolysis, etherification, reduction and condensation, in which the intermediate 2-chloro-4-fluoro-5-nitrophenol could be obtained after the hydrolysis. Due to the irrationality, low yields, and poor stability of available methods, each step of the reaction conditions(type and amount of catalyst, reaction temperature, reaction solvent, reaction time, etc.) were optimized, under which the yield of the reaction was improved to 49.5% and purity to 95%, much higher than those reported in previous patents. The structures of the target compounds were confirmed by IR, 1 H NMR, and the purity of the reaction product were confirmed by HPLC.The second part was the study on the synthesis of thiophene derivatives starting from thioamides. Thiophenes, one of the most important classes of organic heterocyclic compounds, can be found as key structural units in pharmaceuticals, such as Ephedrine, Suprofen, Methapyrilene and so on. Therefore, the research on new methods of synthesizing thiophene derivatives is of great significance.In chapter two, the structure features and important applications in organic chemistry of β-ketothioamides(KTAs) and vinyl azides were gererally reviewed.An efficient protocol for the synthesis of new thiophene framework from β-ketothioamides(KTAs) and vinyl azides via [3+2] cycloaddition process catalyzed by Lewis acid in trifluoroethanol has been built up. The best conditions were established by using 0.1 eq InCl3 as catalyst, trifluoroethanol as solvent, in a molecular ratio of 1:1, stirred for 3 h at 100 oC under N2 by comparing the different kinds and dosages of catalysts, solvents, ratios of materials and temperatures. The structures of all the target compounds were characterized by IR, 1 H NMR, 13 C NMR, and HRMS. The plausible mechanism was also presented.