Development of New and Highly Efficient Synthetic Methods for Bioactive Fluorine-Containing Heterocyclic Compounds Utilizing Characteristics of Fluorine Atom

点击翻译按钮获取中文摘要

beta, beta-Bis (trifluoroacetyl) vinylamine (2) was synthesized quantitatively by the O-N exchange reaction of beta, beta-bis (trifluoroacetyl) vinyl ethers (1) with ammonia water. Trifluoroacetylated vinylamine (2) reacted easily with various aliphatic and aromatic aldehydes in the presence of aqueous ammonia under mild conditions to give 5-trifluoroacetyl-4-trifluoromethyl-1,2-dihydropyrimidines (3) in good yields. Dehydrogenation of 3 with DDQ afforded, in excellent yields, the corresponding fluorine-containing pyrimidines which would show activities on disinfection . Highly functionalized dihydropyrans having trifluoromethyl group were prepared through hetero-Diels-Alder reaction of 1 with isopropenyl methyl ether. Novel aromatic nucleophilic substitution and Subsequent cyclization reaction of N,N-dimethy1-2,4-bis(trifluoroacetyl)-1-naphth-ylamine (4) with 1,2-diamines, 1,2-dithiols and 1,2-dialcohols gave fluorine-containing naphthalene-fused 7-membered heterocycles such as naphthodiazepines, naphthodithiepins and naphthodioxepines in high yields, respectively. Especially naphthazepines have a benzazepinering which is a fundamental skeleton of minor tranquilizers such as medazepam. N-Propargyl-2,4-bis (trifluoroacetyl)-1-naphthylamine (5), synthesized via N-N exchange reaction of 4 with propargylamine, underwent ring forming reacting with amines, thiolates and alcoholates under mild conditions to afford the corresponding 6-trifluoroacetyl-4-trifluoromethylbenzo [h] -quinolines, exhibiting potentially antibacterial activities, in excellent yields. 2,4-Bis- (trifluoroacetyl) -1-naphthylamine (6), prepared easily and cleanly from 4 and aqueous ammonia, reacted readily with various aldehydes in the presence of aqueous ammonia under mild conditions to afford 6-trifluoroacetyl-4-trifluoromethyl-1,2-dihydrobenzo [h] quinazolines, of which dehydrogenation with DDQ gave the corresponding benzo [h] quinazolines in high yields.