Synthesis Of Chloro-3-Methylpyridine Derivatives

Chloro-3-methylpyridine derivatives are important fine chemical intermediates. The fungicides, insecticides and herbicides produced from them have such advantages as high efficiency, low toxicity and safety. In this thesis, three synthetic methods of the title compounds as catalytic-chlorination, oxidization-chlorination, benzyl-amine cyclization were studied and optimized.The catalytic-chlorination method:chloro-3-methylpyridine derivatives were synthesized from3-methylpyridine via chlorination with chlorine in the presence of ferric chloride. The percent conversion of3-methylpyridine reached92.0%. Atypical comprise of the products were the single-chlorinated products31.9%, the dichlorinated products20.6%, the trichlorinated products15.8%and the tetrachlorinated products23.7%. The catalyst cost was reduced by applying ferric chloride to replace palladium chloride.The oxidization-chlorination method:chloro-3-methylpyridine derivatives were synthesized from3-methylpyridine via oxidization and then chlorination with silicon tetrachloride. The percent conversion of3-methylpyridine-N-oxide reached74.0%. A typical comprise of the products were4-chloro-3-methylpyridine45.0%,2-chloro-3-methylpyridine28.8%,2-chloro-5-methylpyridine19.8%and3-chloro-5-methylpyridine6.3%. The synthetic route using silicon tetrachloride to replace POCl3reduced the environmental pollution.The benzyl-amine cyclization method:2-chloro-5-methylpyridine was synthesized from benzylamine, propanal, acetic anhydride and tri-phosgene via condensation, acylation and ring-closure. The total yield was85.0%, and the purity of the product was99.0%. In addition, a novel synthesis of2,3-dichloro-5-methylpyridine was investigated using chloroacetyl chloride to replace acetic anhydride. The total yield was72.5%, and the purity was99.0%. This new synthetic route had such advantages as readily available raw materials, mild reaction conditions and low cost.