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

利用氟原子特性开发生物活性含氟杂环化合物高效合成新方法

基本信息

批准号：
07651058
负责人：
OKADA Etsuji
金额：
$ 1.34万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

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.

通过β， β -二（三氟乙酰基）乙烯醚(1)与氨水的O-N交换反应，定量合成了β， β -二（三氟乙酰基）乙烯胺(2)。三氟乙酰化乙烯胺(2)在氨水存在下，在温和条件下容易与各种脂肪醛和芳香醛反应，生成5-三氟乙酰基-4-三氟甲基-1,2-二氢嘧啶(3)，产率高。用DDQ脱氢得到相应的具有消毒活性的含氟嘧啶，产率高。通过异丙烯甲基醚与1的异diels - alder反应制备了具有三氟甲基的高官能化二氢吡喃。以N，N-二甲基1-2,4-二（三氟乙酰基）-1-萘基胺(4)与1,2-二胺、1,2-二硫醇和1,2-二醇进行新型亲核取代和随后的环化反应，分别高产出萘二氮杂环、萘二硫杂环和萘二氧杂环。特别是萘西卓类药物具有苯并平作用，这是像美达西泮这样的小剂量镇静剂的基本骨架。n -丙炔-2,4-双（三氟乙酰基）-1-萘胺(5)通过4与丙炔胺的N-N交换反应合成，在温和的条件下与胺、硫代酸酯和醇酯发生成环反应，得到相应的6-三氟乙酰基-4-三氟甲基苯并[h] -喹啉，具有潜在的抗菌活性，产率高。2,4-二-（三氟乙酰基）-1-萘胺(6)是由4和氨水制备而成，容易清洁，在氨水存在下，在温和条件下与各种醛反应得到6-三氟乙酰基-4-三氟甲基-1,2-二氢苯并[h]喹唑啉，用DDQ脱氢得到相应的苯并[h]喹唑啉，收率高。