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Preparation of 3-(trifluoromethyl)coumarins

机译:3-三氟甲基香豆素的制备

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摘要

Coumarins constitute an important class of naturally occurring compounds with useful phar-macological activity.~1,2 Numerous coumarins were used as steroid receptor modulators~3 and photopolymerization initiators~4. Some attention has been paid to trifluoromethyl substituted coumarins as fluorescent markers for synthetic proteinases~5,6 and also as laser dyes.~7 Recently, a number of coumarins, inclusive of fluorine containing ones, were patented as optical molecular sensors.~8 In all these applications only 4-trifluoromethyl substituted coumarins were used; they were synthesised by the zinc chloride catalysed condensatio of phenols with 4,4,4-trifluoroacetoacetate (Pechmann reaction).~5,6 Enantioselective cathodic reduction of 4-(trifluoromethyl)coumarin with alkaloids as chiral catalysts was investigated; this resulted in 4-(trifluoromethyl)coumarin with alkaloids as chiral catalysts was investigated; this resulted in 4-(trifluuoromethyl)-3,4-dihydroxoumarin as the amin product (28 yield and 8.4 ee).~9 A number of 3-perfluoroalkyl substituted coumarins were prepared by a sodium hydroxymethanesulfinate (Rongalite) initiated reactions of perfluoroalkyl iodides with coumarins~10 or by reactions of coumarins with perfluoroalkanesulphinates~11 in the presence of oxidants but no 3-(trifluoromethyl)coumarins were obtained by those methods. The only successful preparation of 3-trifluoromethyl substituted coumrins reported so far involves reactions of coumarins with bis(trifluoroacetyl) peroxide.~12
机译:香豆素是一类重要的天然化合物,具有有用的phar-macology活性.~1,2许多香豆素被用作类固醇受体调节剂~3和光聚合引发剂~4。三氟甲基取代的香豆素作为合成蛋白酶~5,6的荧光标记物以及激光染料已经引起了一些关注.~7最近,许多香豆素,包括含氟香豆素,被专利作为光学分子传感器.~8在所有这些应用中,仅使用了4-三氟甲基取代的香豆素;采用氯化锌催化酚与4,4,4-三氟乙酰乙酸酯缩合(Pechmann反应)合成的~5,6 以生物碱为手性催化剂对4-(三氟甲基)香豆素的对映选择性阴极还原;这导致了4-(三氟甲基)香豆素与生物碱作为手性催化剂的研究;由此得到4-(三氟甲基)-3,4-二氢香豆素作为AMIN产物(收率28%,EE8.4%).~9 通过羟基甲烷亚磺酸钠(Rongalite)引发全氟烷基碘化物与香豆素~10的反应,或通过香豆素与全氟烷基磺酸~11的反应,制备了许多3-全氟烷基取代的香豆素,但未通过这些方法得到3-(三氟甲基)香豆素.迄今为止报道的唯一成功的3-三氟甲基取代香豆素制备涉及香豆素与双(三氟乙酰基)过氧化物的反应~12

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