SYNTHESIS OF FLUORINE-CONTAINING ANALOGS OF ANESTHESINE AND NOVOKAINE

Abstract

Methods for the synthesis of methyl, ethyl and butyl esters of meta- and para-pentafluoroethoxybenzoic acids starting with respective hydroxybenzoic acids have been developed. Firstly m- and p-hydroxybenzoic acids were esterificated with respective alcohol, and then obtained esters were treated with trifluoroacetic anhydride giving m- or p-alkyl trifluoroacetoxybenzoates that were treated with SF4 in anhydrous HF medium. Conditions for obtaining esters of meta- and para-pentafluoroethoxybenzoic acids with good yields have been discovered. It has been shown that the yields and ratios of the reaction products depend little on the size of the alkyl radical of the alkoxycarbonyl group, but substantially depend on the temperature, duration of the reaction, and the intensity of mixing. The lack of mixing of the reaction medium during treatment of m- and p-trifluoroacetoxybenzoates with SF4-HF leads to the cleavage of the trifluoroacetoxy group with the formation of the corresponding esters of m- and p-hydroxybenzoic acids. Increasing reaction temperature leads to formation of m- and p-pentafluoroethoxybenzotrifluorides in higher yields. Increasing duration of the reaction affects the same way. Anesthetic activity of obtained esters of meta- and para-pentafluoroethoxybenzoic acids was tested using white outbreed male mice. The esters have higher anesthetic activity compared to anesthesine. Ethyl para-pentafluoroethoxybenzoate exhibits the best anesthetic properties among the compounds obtained. meta-Pentafluoroethoxybenzoic acid has been obtained by means of hydrolysis of ethyl meta-pentafluoroethoxybenzoate. The acid has been treated with equimolar quantity of NaOH solution giving respective salt. The last one was then treated with 2-chloro-N,Ndiethylethanamine in DMF solution, giving analogue of novocaine with pentafluoroethoxy group in the meta-position of the benzene ring. Thus obtained novocaine analogue has also higher anesthetic activity compared to anesthesine.

Keywords

• пентафторетоксигрупа
• чотирифториста сірка
• фтористий водень
• місцеві анестетики