Synthesis of Heterocylic Compounds Bearing Trifluoromethyl Group

甲基酮缩醛与三氟乙酸酐在室温下清洁反应，得到取代的三氟乙酰基乙烯基醚。同样地，原乙酸酯得到-三氟乙酰基乙酮缩醛。在少量硅胶存在下与烯丙醇反应，亲核氧氧交换反应容易进行，高产率地得到取代的三氟乙酰基乙烯基烯丙基醚。当这些烯丙基醚在硅胶中加热时，发生Claisen重排得到3-烯丙基-1，1，1-三氟丙酮。然后，通过双官能亲核试剂，如联氨和羟胺处理，这些二酮被衍生为含有三氟甲基和烯丙基的各种杂环。利用N，N-dimethyl-2.4-bistrifluoroacetylnaphthylamine与不同的胺进行了亲核芳香氮-氮交换反应。该化合物被发现经过有趣的环化反应，通过吸附在硅胶上并在没有溶剂的情况下在78℃下保持24小时，以几乎定量的产率得到含氟的萘恶嗪。与氨基酸、联胺和羟胺反应，分别得到苯并吲哚、萘并吡唑和萘异恶唑。这些含氟化合物的生理活性分析目前正在进行中。

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.