Yasuo Maki

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.

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.

Facile syntheses of 4-(trifluoromethyl)-L-spinacine and 4-(trifluoromethyl)spinaceamine

Abstract Reaction of L-histidine with trifluoroacetaldehyde ethyl hemiacetal (TFAE) in boiling water provides 4-(trifluoromethyl)-L-spinacine, 4-(trifluoromethyl)-L-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid, in near quantitative yield. The product contains two diastereoisomers in the ratio 68 : 32. The isomers were separated (silica gel) as their protected derivatives, 5-N-(trifluoroacetyl)-4-(trifluoromethyl)-L-spinacine methyl esters, and were regenerated by acid hydrolysis. The analogous reaction with histamine provides 4-(trifluoromethyl)spinaceamine in 91% yield.

A facile synthesis of 1-trifluoromethyl-β-carboline

Abstract The two-step synthesis of the title compound has been achieved by Mannich-type condensation of tryptamine with trifluoroacetaldehyde, followed by dehydrogenation with selenium dioxide; the overall yield was 79.3%.

Synthesis of 1-thrifluoromethyl-β-carboline derivatives

Abstract Benzene-ring substituted 1-trifluoromethyl- β -carbolines (IV) were synthesized in 23 ~ 27% overall yield by selenium dioxide dehydrogenation of the corresponding 1-trifluoromethyl-1,2,3,4-tetrahydro-β-carbolines (II); the latter compounds were obtained in high yield by Mannich-type condensation of the respective tryptamines with trifluoroacetaldehyde. Partial dehydrogenation of II with potassium permanganate provide 1-trifluoromethyl-3,4-dihydro- β -carbolines (III). L-tryptophan gave, following condensation, esterification and dehydrogenation, 3-carboethoxy-1-trifluoromethyl-β-carboline (IVf) in 84.8% overall yield. The halogenation and nitration of 1-trifluoromethyl-β-carboline (IVa) were also examined.

Oxidation of Fluorine-Containing Alcohol with Chlorine

1H,1H,5H-ペルフルオルアミルアルコールをジフルオルテトラクロルエタンに溶解し,いろいろな実験条件下で塩素を導入して酸化を行なった。反応生成物として4H-ペルフルオルバレルアルデヒドのほかに4H-ペルフルオルブチルクロリド,4H-ぺルフルオル吉草酸1H,1H,5H-ペルフルオルアミルおよび4H-ペルフルオル吉草酸の4種の化合物が生成することを確認した。アルデヒドは45℃ 付近で最高収率33.7%を示し,これより反応温度が低い場合はエステルが,逆に高い場合はクロリドが主生成物となることを明らかにするとともに,生成機構についても考察した。