Synthesis of Heterocylic Compounds Bearing Trifluoromethyl Group

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Reaction of acetals of methyl ketones with trifluoroacetic anhydride occurred cleanly at room temperature to give -substituted -trifluoroacetylvinyl ethers . Likewise orthoacetates gave -trifluoroacetylketene acetals. On treatment of with allyl alcohols in the presence of a small amount of silica gel nucleophilic oxygen-oxygen exchange reaction proceeded easily to afford -substituted -trifluoroacetylvinyl allyl ethers in high yields. When these allyl ethers were heated with silica gel there occurred Claisen rearrangement to give 3-allyl-1,1,1-trifluoro-acetone . These -diketones were then derived to various heterocycles bearing trifluoromethyl and allyl groups by treatment of them with bifunctional nucleophilic reagents such as hydrazines and hydroxylamine. Nucleophilic aromatic nitrogen-nitrogen exchange reaction was successfully performed with the use of N,N-dimethyl-2.4-bistrifluoroacetylnaphthylamine with various amines. The compound was found to undergo interesting cyclization to give fluorine containing naphtho-oxazine in almost quantitative yields by adsorbing on silica gel and keeping it at 78 C for 24 hours without solvent. Reactions of with amino acids, hydrazines and hydroxylamine gave benzindoles, naphthopyrazoles and naphthoisooxazoles, respectively. Assays of these fluorine-containing compounds for physiological activities are now in progress.