Trifluoromethylation Reaction And Its Application In Drug Synthesis

Trifluoromethyl groups have strong electron-withdrawing and lipophilic properties,and their incorporation into organic compounds can significantly alter the acidity,dipole distance,polarity,lipophilicity,chemical and metabolic stability of the compounds.The compounds contain trifluoromethyl groups have been widely used in medicine,pesticides and materials.Trifluoromethyl ketone is a particularly important class of compounds among many trifluoromethyl-containing molecules.As a variety of enzyme inhibitors,it has strong biological activity;at the same time,it also synthesizes other trifluoromethyl derivatives as important intermediates.This dissertation focuses on the direct trifluoromethylation of aldehydes and their derivatives involved in sodium trifluoromethanesulfinate,it providing new ideas for the synthesis of trifluoromethyl ketones with various substituent groups.The work include:1.Trifluoromethylation of aldehydes and their derivativesTrifluoromethyl ketones?TFMKs,RCOCF₃?are important components of many biologically active compounds and are widely used structures in the synthesis of fluorinated molecules.N,N-Dialkylfluorenes have been widely used as a stable,readily available alternative to carbonyl-containing compounds and imines.On the other hand,the oxime structure can provide TFMK when it is hydrolyzed under acidic conditions.We have developed a synthesis route for the trifluoromethylation of N,N-disubstituted fluorenes using Langlois reagent?CF₃SO₂Na?without transition metal catalysis and with less cost.This method is simple to operate,has mild reaction conditions and highlights excellent functional group tolerance.This reaction provides a convenient and practical method for providing trifluoromethylated structural units having a variety of functional groups.2.Trifluoromethylation of ?,?-unsaturated aldehydes and their derivativesThe ?,?-unsaturated structures occur in many important pharmaceutical synthesis intermediates,and the trifluoromethylated products of ?,?-unsaturated aldehydes and their derivatives can be hydrolyzed under certain conditions to produce active trifluoromethyl groups.Because of the ketone structure,it is of great significance to find a novel,highly regioselective method for the formation of trifluoromethylated products of hydrazine ?,?-unsaturated aldehydes and their derivatives.In this paper,we have identified a mild and rapid method for the screening of reaction conditions,and synthesized a series of target products with high regioselectivity under the condition of no transition metal catalysis.The method has the advantages of economical and environmental friendly,wide application range.