Imidazoles, 2-trifluoromethyl-, hydrolysis

Imidazole, 2,4,5-trichloro-1-methyl-chlorination, 5, 398 Imidazole, 2,4,5-trideutero-iodination, 5, 401 Imidazole, 1-trifluoroacetyl-reactions, 5, 451-452 Imidazole, 2-trifluoromethyl-hydrolysis, 5, 432 Imidazole, 2,4,5-triiodo-nitration, 5, 396 synthesis, 5, 400 Imidazole, 1,2,4-trimethyl-photolysis, 5, 377 rearrangement, 5, 378 Imidazole, 1,2,5-trimethyl-photochemical rearrangement, 5, 377 rearrangement, 5, 378 Imidazole, 1,4,5-trimethyl-bromination, 5, 399 3-oxide... 

Using l,l,l-trifluoro-2,3-alkanediones, obtained as monohydrates from the acidic hydrolysis of 3-(dialkylhydrazino)-l,l,l-tiiflnoro-2-alkanones, Kamitori reported the synthesis of 4-(trifluoromethyl)imidazoles (Scheme 34) [48]. Two slightly different methods were used to construct the imidazole ring around the diketone skeleton. While the room-temperature reactions of diketones and aliphatic aldehydes in the presence of excess anunonia afforded the 4-(trifluoromethyl)imid-azoles, the reactions of diketones with aromatic aldehydes were conducted in hot acetic acid in the presence of excess ammonium acetate. The later protocol was also used for the synthesis of a 2,4-bis(trifluoromethyl)imidazole. 

Hojo reported a selective synthesis of 4-(trifluoromethyl)imidazoles (Scheme 35) [49], The diketones, prepared from aldehyde dialkyl hydrazones via the hydrolysis of 3-(dialkylhydrazino)-l,l,l-trifluoro-2-aIkanone intermediates, were treated with 1,1-dimethylhydrazine to afford the adduct. These adducts were generally unstable even at room temperature and, thus, were immediately dehydrated using POCI3-pyridine to afford 3-aryl-l,l,l-trifluoropropane-2-,3-dione-2-dimethylhydrazone. Intramolecular cyclization of these hydrazones in refluxing toluene afforded the desired 4-(trifluoromethyl)imidazoles. 

Trifluoromethylpurines have been prepared mainly through formation of the pyrimidine ring starting from highly functionalised imidazoles. 5-Amino-4-(cyanoformimidoyl)imidazole 29 reacted rapidly with neat trifluoroacetic anhydride to give the 6-cyano-2-trifluoromethylpurine 30 (20 °C, 10 min, 52 %) [55] (Scheme 13). However, hydrolysis to the 6-carboxamidopurine 31 was observed when the reaction was carried out over several days [55,56]. This latter transformation has been applied to prepare 9-(3-hydroxy-propyl)-2-trifluoromethyl-9H-purine-6-carboxamide [57]. 

---