Shozo Fujii

Nucleophilic substitution of pentafluorobenzes with imidazole

Abstract The imidazole substitution of pentafluorobenzenes C6F5R: R = CN, NO2, CO2C2H5, CHO, I, Br, Cl, H) occurred mainly at the para -position to R and corresponding 1-(4′-R-tetrafluorophenyl)imidazoles were obtained in good yields. The reactivity varied markedly with the substituents: nitro- or cyanopentafluorobenzene easily reacted at ambient temperature without any bases; however, methyl- or methoxypentafluorobenzene failed to react even at 100°C in the presence of a strong base.

An Electrochemical Approach for the Synthesis of Perfluoroalkylated Purine and Indole Analogues of Plant Growth Regulators

In an effort to prepare new fluorine-containing molecules as analogues of Plant Growth Regulators (PGRs), the indirect electrochemical reduction, by means of an aromatic anion mediator, of perfluoroalkyl halides in the presence of purine and indolyl anions was carried out. The corresponding C-perfluoroalkylated products were obtained by an SRN1 mechanism, in moderate to good yields, and biological activity of some of the products was evaluated.

(S)-(+)-4,4,4-Trifluoro-3-(indole-3-)butyric acid, a novel fluorinated plant growth regulator

Racemic 4,4,4-trifluoro-3-(indole-3-)butyric acid (TFIBA) has been synthesized and shown to inhibitAvena coleoptile elongation. (S)-(+)-TFIBA (fig. 1), which was prepared by an enzymatic method and markedly promotes root growth of Chinese cabbage, lettuce and rice plants, is a novel fluorinated plant growth regulator. Activity of the (S)-(+)-enantiomer of TFIBA was 10-fold greater than that of the (R)-(−)-enantiomer in the first two plant species and 5-fold greater in rice.

Synthesis of α-trifluoromethylated indoleacetic acid: a potential peroxidase-stable plant growth regulator

Abstract A novel trifluoromethylated indoleacetic acid analog was synthesized by condensation of indole with methyl trifluoropyruvate, and the subsequent reduction. The presence of a trifluoromethyl group at the α-position protected this indoleacetic acid from the oxidation of horseradish peroxidase.

Thermal condensation of imidazole with trifluoroacetaldehyde

Abstract The title condensations provide the corresponding (1′-hydroxy-2′,2′,2′-trifluoroethyl)indoles. Indole itself, 1-methylindole and 2-methylindole gave 3-adducts in yields of 77%, 49% and 84%, respectively. 3-Substituted indoles (3-methylindole, ethyl indole-3-acetate and indole-3-ethyl acetate) afforded 2-adducts in yields of 69%, 21% and 23%, respectively. The indole adduct eliminates water at 137°C to form a transient 3-(trifluoromethylmethylene)indolenine, which reacts rapidly with nucleophiles including indole.

Synthesis and alkaline hydrolysis of (pentafluoroethyl)imidazoles

Abstract Photochemical ring substitution of the N-trifluoroacetyl derivatives of histamine and of L-histidine methyl ester by pentafluoroethyl radical provides the corresponding 2- and 4-pentafluoroethylated products in yields of 19% and 27%, respectively. Alkaline hydrolysis converts the 2-pentafluoroethyl group to trifluoroacetyl. The reaction mechanism, involving a diazafulvene intermediate, is analogous to that elucidated for (trifluoromethyl)imidazoles; however, the pentafluoroethyl group is markedly more reactive to hydrolysis than the trifluoromethyl group. For imidazole derivatives, the ratio of reactivities is 75 at C-2 and 40 at C-4. The hydrolysis of 4-(pentafluoroethyl)histamine affords the bicyclic product, 4-(trifluoromethyl)-6,7-dihydro-1H-imidazo[4,5-c]-pyridine in 65.4% yield.

Thermal condensation of substituted imidazoles with trifluoroacetaldehyde

Abstract The title condensation provides the corresponding (1′-hydroxy-2′,2′,2′-trifluoroethyl)imidazoles in yields dependent on the electronic nature of the substituent: ortho-para directors promote the reaction while meta directors retard it strongly. 1-Alkylimidazoles gave only 2-adducts. 2-Substituted imidazoles yielded 4(5)-adducts together with small amounts of 4,5-bis-adducts. 4(5)-Substituted imidazoles provided 5(4)-adducts as the main products together with 2-adducts and 2,5(4)-bis-adducts.

Synthesis and polymerization of ethynylthiophenes and ethynylfurans containing trifluoromethyl groups

Abstract Fluorination of thiophenedicarboxylic acid with sulfur tetrafluoride in the presence of anhydrous hydrogen fluoride provided mono and bis(trifluoromethyl)thiophenes in moderate yields. Ethynylthiophenes and ethynylfurans containing trifluoromethyl groups were prepared via 2,2-dichloro-1-fluorovinyl compounds. In polymerizations using transition metal catalysts, 3-ethynylthiophenes gave polymers in high yields, which were soluble in THF and/or fluorocompounds, while 2-ethynylthiophenes polymerized in low yields. In γ-ray induced polymerization, only 2,5-bis(trifluoromethyl)-3-ethynylthiophene afforded the corresponding polymers. Thermal decomposition temperature of polymers obtained increased by introduction of the trifluoromethyl groups as well as the methyl groups.

Facile perfluoroalkylation of uracils and uridines at the C-5 position

Abstract Perfluoroalkylation at the C-5 position of uracil has been achieved in yields of 38–56% by the reaction of its bis(trimethylsilyl) derivative with bis(perfluoroalkanoyl) peroxides and the hydrolytic deprotection of the silylated products. A substituent or nitrogen replacement at C-6 does not interfere with perfluoroalkylation at C-5, but no significant reaction occurs at C-6 when C-5 is blocked.

Enzymatic preparation of both enantiomers of 4,4,4-trifluoro-3-(indole-3-)butyric acid, a novel plant growth regulator

Abstract Efficient optical resolution of both enantiomers of 4,4,4-trifluoro-3-(indole-3-)butyric acid (TFIBA), a novel plant growth regulator, was achieved by two enzyme-catalyzed steps using lipase AK (a lipase from Pseudomonas sp.). S-(+)-TFIBA and R-(−)-TFIBA ethyl ester were prepared with 98% e.e. by the first step of lipase-catalyzed enantioselective hydrolysis in a 0.1 M acetate buffer (pH 5.0) containing 10% t-BuOH at 55°C for 45 h. the % e.e. in S-(+)-TFIBA was further improved to >99% e.e. by lipase-catalyzed enantioselective esterification with ethanol in heptane and subsequent hydrolysis using PLE-A (an esterase from pig liver). R-(−)-TFIBA was prepared with >99% e.e. by the second step of lipase-catalyzed enantioselective hydrolysis under the same conditions as described above and subsequent hydrolysis using PLE-A. The root growth-promoting activity of S-(+)-TFIBA was about 10-fold higher than that of R-(−)-TFIBA for black matpe, Chinese cabbage, lettuce, and rice plants (Ohgonbare and Tan-ginbozu).