Takuichi Miki

Reactions of trifluoromethyl ketones. IX. Investigation of the steric effect of a trifluoromethyl group based on the stereochemistry on the dehydration of trifluoromethyl homoallyl alcohols

Abstract In a previous paper we reported that a trifluoromethyl group behaves as a larger substituent than a butyl or a phenyl group and slightly larger than a sec-butyl group in ene reactions of trifluoromethyl carbonyl compounds. Dehydration of trifluoromethyl homoallyl alcohols, which are obtained by the ene reaction of trifluoromethyl ketones, has now been extensively investigated to compare further the steric effect of a trifluoromethyl group with those of other substituents. A trifluoromethyl group behaves as a substituent as large as a cyclohexyl group and a little smaller than a sec-butyl group. Differences between steric effects in the ene reaction and in the dehydration are discussed.

Trifluoromethylation of Tocopherols

Abstract γ- and δ-Tocopherol were converted to iodo compounds, which were trifluoromethylated with trifluoromethyl iodide and copper powder in HMPA.

Diels-Alder reactions of trifluoromethyl dienes obtained from ene reactions of trifluoromethyl carbonyl compounds☆

Abstract The ene reactions of trifluoromethyl carbonyl compounds give products which may be dehydrated to trifluoromethyl dienes; the Diels Alder reaction of these have been investigated. The dienes from trifluoromethyl ketones hardly reacted, probably because the steric effect of the trifluoromethyl group prevents the diene from taking up a cisoid form. Dienes obtained from the ene reaction of trifluoroacetaldehyde have one substituent at a terminal position and react with dienophiles to give trifluoromethylated cyclohexene derivatives.

Synthesis of fluorine analogs of hematoporphyrin

With the aim of obtaining a porphyrin derivative useful for diagnosis and therapy of cancer, fluorine analogs of hematoporphyrin, which had trifluorohydroxyethyl group(s) in the place of hydroxyethyl groups, were synthesized by the reaction of deuteroporphyrin dimethyl ester with trifluoroacetaldehyde in the presence of aluminum chloride. Preliminary results of biological tests of the products showed that the hexafluoro analog of hematoporphyrin accumulates to Human liver cancer cells more selectively than other fluorine analogs

Synthesis of Fluorine Analogues of Protoporphyrin

Abstract With intention of obtaining a porphyrin derivative useful for diagnosis and therapy of cancer, fluorine analogues of protoporphyrin, in which the vinyl group(s) were replaced by difluorovinyl group(s), were synthesized by the reaction of the formylporphyrins with sodium chlorodifluoroacetate in the presence of triphenylphosphine.

A new method for synthesis of fluorine compounds using an unusual Grignard reaction of halothane with ketones

Abstract The reaction of 2-bromo-2-chloro-1,1,1-trifluoroethane (1) with 2-octanone (3a) in the presence of magnesium did not give 2-chloro-1,1,1-trifluoro-3- methyl-3-nonanol (4a) but 2-bromo-2-chloro-1,1,1-trifluoro-3-methyl-3- nonanol (5a) and 2-chloro-1,1-difluoro-3-methyl-1-nonen-3-ol (6a). This suggested that the primary Grignart reagent, 1-chloro-2,2,2-trifluoroethylmagnesium bromide (2), reacted with excess 1 rather than with the ketone 3a to give 1-bromo-1-chloro-2,2,2-trifluoroethylmagnesium bromide (8), which added to the ketone to give 5a. Detection of 1,1,1-trifluoro-2-chloroethane supported this mechanism. Compound 5a was formed preferentially at −53 °C, and on warming to 0 °C, the amount of 5a decreased while that of 6a increased. Therefore, compound 6A must be formed by reduction of 5a with excess magnesium. Treatment of 6a with hydrogen fluoride gave 2-chloro-1,1,1-trifluoro-3-methyl- 2-nonene (9a). Cyclohexanone (3b) and acetophenone (3c) reacted similarly to give corresponding products.

Synthesis of fluorine analogues of vitamin e

Abstract The biological activity of Vitamin E is believed to be related to the anti-oxidative property of the 6-chromanol structure. Vitamin E comprises a number of isomers, with differences in the number of methyl substituents on the benzene ring and the structure of the side chain at the 2-position. Vitamin E is believed to combine with the cell membrane and to suppress the oxidation of unsaturated fatty acids on the membrane. If this is correct, the differences of activity of Vitamin E compounds must be attributed to differences in their affinity for the membrane besides difference of the electronic property of the 6-chromanol part. Thus, we synthesized analogues of Vitamin E with fluorine substituents on the side chain or on the benzene ring, since these substituents might change the lipophilicity and/or the electronic property of Vitamin E. Synthesis of these analoques and their biological properties will be presented.