Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia.
Molecules. 2018 Nov 30;23(12):3163. doi: 10.3390/molecules23123163.
Mechanochemical ball milling catalytic transfer hydrogenation (CTH) of aromatic nitro compounds using readily available and cheap ammonium formate as the hydrogen source is demonstrated as a simple, facile and clean approach for the synthesis of substituted anilines and selected pharmaceutically relevant compounds. The scope of mechanochemical CTH is broad, as the reduction conditions tolerate various functionalities, for example nitro, amino, hydroxy, carbonyl, amide, urea, amino acid and heterocyclic. The presented methodology was also successfully integrated with other types of chemical reactions previously carried out mechanochemically, such as amide bond formation by coupling amines with acyl chlorides or anhydrides and click-type coupling reactions between amines and iso(thio)cyanates. In this way, we showed that active pharmaceutical ingredients Procainamide and Paracetamol could be synthesized from the respective nitro-precursors on milligram and gram scale in excellent isolated yields.
用易得且廉价的甲酸铵作为氢源，通过机械化学球磨催化转移氢化（CTH）芳香族硝基化合物，是一种简单、方便且清洁的方法，可用于合成取代苯胺和一些具有药用相关性的化合物。机械化学 CTH 的适用范围很广，因为还原条件可以耐受各种官能团，例如硝基、氨基、羟基、羰基、酰胺、脲、氨基酸和杂环。所提出的方法还成功地与以前通过机械化学进行的其他类型的化学反应相结合，例如通过将胺与酰氯或酸酐偶联形成酰胺键，以及胺和异（硫）氰酸酯之间的点击型偶联反应。通过这种方式，我们表明可以从相应的硝基前体出发，在毫克和克级规模上以优异的分离收率合成活性药物成分普鲁卡因胺和对乙酰氨基酚。
