Study On The Synthesis Of N-butyl Flufenamate And 10-(3-chloropropyl)-2-(trifluoromethyl)phenothiazine

Organic fluorides were chemical stabilization, therapeutically active compounds owing to their strong electronegativity of fluorine, high energy of carbon-fluorine bond and fluorine atomic radium analog to hydrogen's , and widely utilized to the pharmaceuticals.It was synthesized that flufenamic acid and normal butyl flufenamate (nonsteroid antiinflammatory drugs), 10-(3-chloropropyl)-2-(trifluoromethyl) phenolthiazine (phenothiazines pharmaceutical intermediate), starting from meta-trifluoromethyl phenylamine.The optimum synthesis techniques of flufenamic acid in the presence of active cupric powder : n( meta-trifluoromethyl phenylamine): n(potassium carbonate ) :n (ortho-chlorobenzoic acid) = 2.5:0.5 : 1, W (catalyst ): W (ortho-chlorobenzoic acid) =0.01 : 1, react 6 hours at 120℃. After screening the best catalyst was Cu powder and cuprous chloride mixture. When equimolar Cu powder and cuprous chloride was used as catalyst, the yield reached 73.6 % on the aforesaid conditions.The optimum esterification techniques of flufenamic acid: n (Flu- fenamic acid): n(n-butanol)=1:1.5, flufenamic acid react with n-butanol at 126～135℃for 8 hours in the presence of p-methyl- phenylsulfonate, n-Butyl flufenamate was get at the yield of 95.1%.The new technique of 10-(3-chloropropyl)-2-(trifluoromethyl)phe- nolthiazine was studied by the cyclization after decarboxylation of flufenamic acid and then condensation with 3-bromo-1-chloropropane. N-phenyl-3-trifluoromethylphenylamine yields 85.3 % when flufenamic acid decarboxylated at 235℃for 4 hours.The synthetic optimum technique of 2-trifluoromethylphenothiozine was n (N-phenyl-3-trifluoromethylphenylamine): n (sulphur)=1.5 : 2, W(I₂): W (N-phenyl-3-trifluoromethylphenylamine)=1: 35, reaction at 140～150℃for 3.5 hours. The yield was 43.4%The synthetic optimum technique of 10-(3-chloropropyl)-2-(tri- fluoromethyl)phenothiazinesyn was n(2-trifluoromethylphenothiozine): n(3-bromo-1-chloropropane): n(sodium amide)=1:1.5:1.5, reaction at 135℃for 18 hours. The yield was 31.7%.