Erdelmeier I, Tailhan-Lomont C, Yadan J C
OXIS International SA, 1 place Boieldieu, 75002 Paris, France.
J Org Chem. 2000 Dec 1;65(24):8152-7. doi: 10.1021/jo000418f.
Benzisoselenazolines 15 and benzisoselenazines 21, designed as low molecular weight mimics of glutathione peroxidases, were synthesized for the first time. Starting from amines 13 and 14, a smooth introduction of selenium in nonactivated aryl bromides using KSeCN in the presence of CuI was developed. An equimolar quantity of CuI and the presence of Et(3)N as a base are necessary to achieve a complete conversion of the starting material. The reaction is feasible in various solvents such as DMF, acetonitrile, and THF. The desired new Se-N heterocycles 15 and 21 were isolated under optimized conditions in yields of 82 and 68%, respectively. Experiments have been conducted with various copper(I) and copper(II) salts, a chloroamine 17, an aryl bromide 18, and an N-acylated amine 19 to show the scope and the limitations of this method. The previously unknown sulfur analogues 20 and 22 have been synthesized in moderate yields using a slightly modified procedure. Finally, a mechanistic scheme has been proposed to discuss some interesting findings, which were obtained during the optimization process of this new introduction of selenium.
首次合成了作为谷胱甘肽过氧化物酶低分子量模拟物设计的苯并异硒唑啉15和苯并异硒嗪21。以胺13和14为起始原料，开发了在碘化亚铜存在下使用硒氰化钾在未活化的芳基溴中顺利引入硒的方法。需要等摩尔量的碘化亚铜和作为碱的三乙胺的存在才能使起始原料完全转化。该反应在各种溶剂如N,N - 二甲基甲酰胺、乙腈和四氢呋喃中都是可行的。在优化条件下分离得到了所需的新型硒 - 氮杂环化合物15和21，产率分别为82%和68%。已用各种铜（I）和铜（II）盐、氯胺17、芳基溴18和N - 酰化胺19进行了实验，以展示该方法的适用范围和局限性。使用略有修改的程序以中等产率合成了先前未知的硫类似物20和22。最后，提出了一个机理方案来讨论在这种新的硒引入优化过程中获得的一些有趣发现。
