SYNTHESIS OF PENTAFLUOROETHOXYBENZOIC ACIDS

Abstract

One of the benzamide derivatives is procainamide, a drug with local anesthetic and antiarrhythmic activity. At the same time, procainamide analogues bearing trifluoroethoxy group in positions 2 and 3 of the aromatic nucleus possess a higher antiarrhythmic activity compared to procainamide. However, no procainamide analogues bearing the –OCF2CF3 group at the aromatic ring have been reported. The introduction of pentafluoroethoxy group into the aromatic ring of procainamide may have a favorable effect on the anesthetic properties of the compounds obtained. Therefore, it was interesting to develop methods for the preparation of benzoic acids containing the –OCF2CF3 group in the aromatic ring, that could be used to synthesize the fluorine-containing analogues of procainamide. We have developed a method for the synthesis of benzoic acids containing the group –OCF2CF3 in different positions of the benzene ring, from the corresponding methyl hydroxybenzoates. Methyl ortho-, meta-, and para-hydroxybenzoates were heated with trifluoroacetic anhydride in an autoclave at 150 °C for 5 hours giving the corresponding methyl trifluoroacetoxybenzoates. Treatment of methyl ortho-trifluoroacetoxybenzoates with sulfur tetrafluoride in the hydrogen fluoride medium led to complete tarring of reaction mixture even at room temperature. At the same time, after fluorination of methyl meta- and para-trifluoroacetoxybenzoates with sulfur tetrafluoride in the hydrogen fluoride medium, a mixture of pentafluoroethoxybenzotrifluorides, pentafluoroethoxybenzoyl fluorides and methyl pentafluoroethoxybenzoates was formed. The resulting mixture was treated with sodium hydroxide solution at room temperature, then the pentafluoroethoxybenzotrifluorides were steam distilled off. The remaining reaction mixture was acidified, filtered, and corresponding meta- or para-pentafluoroethoxybenzoic acids were obtained with good yields.

Keywords

• пентафторетоксигрупа
• чотирифториста сірка
• фтористий водень
• місцеві анестетики