One-Pot Construction Of C-O And C-Cl Bonds Via Decarboxylation Of Picolinic Acids

Aryl ether moieties represent interesting structural moities in natural products and biologically active compounds. Therefore, the development of new method for the synthesis of aryl ether derivatives has attracted considerable attention. Aryl ethers are often synthesized from aryl carboxylic acids via decarboxylation because the aryl carboxylic acids are stable and easily available with low-cost. The transition-metal catalyzed decarboxylation of aryl carboxylic acids for the synthesis of aryl ethers has been reported so far. However, the metal-free decarboxylation of aryl carboxylic acids is still remained a challenge. In this thesis, a new method was developed for metal-free one-pot construction of C-O and C-Cl bonds via decarboxylation of picolinic acids. The corresponding products 2-(2-(2-chloroethoxy)-ethoxy) pyridine derivatives were obtained in good to execellent yields.The decarboxylation of picolinic acid was selected as a model substrate to optimize the reaction conditions. The effect of oxidant, loading of tert-butyl hypochlorite and p-chloranil, and reaction temperature was investigated. It was found that when the reaction was treated with tBuOCl as Cl resource and oxidant (1.67 equiv),p-chloranil as oxidant (20 mol%),1, 4-dioxane as solvent and reactant, at 110℃ under N2 atmosphere, a best result was obtained. The target reaction proceeded smoothly under optimized reaction conditions to give the corresponding products 2-(2-(2-chloroethoxy)-ethoxy)pyridine derivatives in good to excellent yields. The electronic property (electron-donating or electron-withdrawing) of substitutent bearing on pyridine ring did not enfluence on the reactivity of picolinic acids expect for the 6-position substituent. However, the reaction of picolinic acid bearing a substrate at 6-position of pyridine resulted in no reaction. All of products were characterized by 1H-NMR,13C-NMR, IR, and HRMS analysis.