Study On Synthesis Of 3-(Trifluoromethyl) Pyridine-2-sulfonamide

Pyridine derivatives have wide applications in the fields of pesticide, pharmaceuticals, dyes, perfumes, surfactants, rubber chemicals, feed additives, food additives, adhesives, synthetic materials and daily chemicals for their higher biological activities, lower toxicities, and higher systemic action and selectivity. They can synthesis multiple intermediates by chlorination, fluorination and amination, which is finding wide application in fine chemical industry and enjoying great prospects as far as deep processing is concerned. Pyridine derivatives are one of the fine chemicals that are in urgent need of development in our country.Fluorine leaves nobody indifferent; it inflames emotions, be that affections or versions. As a substituent, it is rarely boring, always good for a surprise, but often completely unpredictable. The above quote, although somewhat melodramatic, does capture the reaction of many researchers to the effects of fluorine substitution on chemical and biological activities.With perhaps the exception of fluorine steric interactions, substituent effects on reactive intermediates (carbocations, carbanions, carbenes and free radicals) that underlie the chemical reactivity of fluorinated compounds are now rather well understood and fairly predictable. By contrast, fluorine substituent effects on physical properties are important to compound binding, absorption, and transportation that can impact biological activity, often less well understood from experience. Special properties of F are as follows: high electronegativity; relatively small size; very low polarizability; tightly bound, three non-bonding electron pairs; excellent overlap between F 2s and 2p with corresponding orbitals of other second period elements.In this paper, prepared were 2-mercapto-3-trifluoromethylpyridine,3-(trifluoromethyl) pyridine-2-sulfonyl chloride and 3-trifluoromethyl-pyridine-2-sulfonamide. The products and their intermediates were characterized by HPLC, IR and 1HNMR. Moreover, the optimized reacting conditions and the reaction mechanisms were discussed according to the effects of the different reaction factors.2-mercapto-3-trifluoromethylpyridine was synthesized by 2-chloro-3-(trifluoromethy--1)pyridine and sodium persulfide in the anhydrous ethanol system by one-step sulfhydrylation reaction in 50.0% yield. The reaction factors, such as sulfhydrylating agent, solvent, moisture and dosage were discussed. The preparation method has the advantages of simple process, high purity (>99%), high yield, and low requirements to application. 3-(trifluoromethyl)pyridine-2-sulfonyl chloride was obtained from 2-mercapto-3-trifluoro--methylpyridine via chlorideization oxidation reaction in acetic acid- water system at-10℃in 74.1% yield.3-Trifluoromethylpyridine-2-sulfonamide with the purity of 99.6% was also prepared from 3-(trifluoromethyl) pyridine-2-sulfonyl chloride through amination reaction at 0℃or lower in 90.2% yield. So the total yield was as high as 33.5% calculated with 2-chloro-3-(trifluoromethyl)pyridine.3-(trifluoromethyl)pyridine-2-sulfonyl chloride was obtained from 2-Amino-3-(trifluo-romethyl)pyridine through diazotization reaction and chlorosulfonation reaction in 73.6% yield, meanwhile investigated the effect of amount of hydrochloric acid and Sodium bisulfite.Adopting the "one-pot" method,3-trifluoromethylpyridine-2-sulfonamide with the purity of 99.0% was synthesized from 3-(trifluoromethyl) pyridine-2-sulfonyl chloride reaction mixture through amination reaction below 0℃in 90.0% yield. The over yield was 66.2% calculated with 2-amino-3-(trifluoromethyl)pyridine.3-(trifluoromethyl)pyridine-2-sulfonyl chloride was prepared by 2-chloro-3-(trifluoro-methyl)pyridine and 2-amino-3-(trifluoromethyl)pyridine with different methods,and the approach is of great value in industrial development of pyridine derivatives.