透過(1)一價銅催化布Buchwald–Hartwig反應及 (2)親電子性芳香環取代反應合成苯併咪唑化合物

Abstract

2-Aminobenzimidazole是重要含氮雜環結構，廣泛存在許多具有生物活性的分子中，本論文主旨為合成2-aminobenzimidazole的相關衍生物。 第一部份中，我們開發從o-bromobenzonitrile以簡單快速的方式合成2-(N-alkylamino)benzimidazoles，反應由o-bromobenzonitrile透過Tiemann重排反應形成o-bromophenylcyanamide，再與一級和二級烷基胺在一價碘化銅與1,10-phenanthroline催化下，進行Buchwald–Hartwig 碳-氮鍵生成反應，即可製備一系列的2-(N-alkylamino)benzimidazole衍生物。 第二部份中，我們開發從benzonitrile以簡易的方式合成1-alkyl-2-(tosylamino)benzimidazoles，反應由benzonitrile透過Tiemann重排反應生成phenylcyanamides，接著進行烷基化和羥胺的加成即可生成N-aryl-N-alkyl-N’-hydroxyguanidine，最後加入TsCl活化氮上羥基脫去並進行分子內親電子性芳香取代反應，可製備一系列1-alkyl-2-tosylaminobenzimidazole衍生物。2-Aminobenzimidazole derivatives are important nitrogen-containing heterocycles which often were embedded in many biologically active molecules. This thesis focuses on the synthesis of 1-aminobenzimidazole derivatives from benzonitriles. In the first part, a direct approach for the synthesis of 2-(N-alkylamino)benzimidazoles from o-bromobenzonitriles was developed. The reaction of o-bromophenylcyanamides, obtained from o-bromobenzonitriles via Tiemann rearrangement, with various primary and secondary alkylamines employing of copper(I) iodide and 1,10-phenanthroline in 1,4-dioxane via Buchwald–Hartwig amination reaction protocol afforded a series of 2-(N-alkylamino)benzimidazoles. In the second part, a metal-free approach for the synthesis of 1-alklyl-2-(tosylamino)benzimidazoles from benzonitriles was developed. A series of N-aryl-N-alkyl-N’-hydroxyguanidins were obtained from N-alkylation followed by hydroxylamine addition of phenylcyanamides, synthesized from benzonitriles via Tiemann rearrangement. p-toluenesulfonyl chloride-promoted intramolecular electrophilic aromatic substitution reaction of N-aryl-N-alkyl-N’-hydroxyguanidins afforded a series of 1-alkyl-2-(tosylamino)benzimidazoles.