Onwukamike Kelechukwu Nnabuike, Grelier Stéphane, Grau Etienne, Cramail Henri, Meier Michael A R
Institute of Organic Chemistry (IOC), Materialwissenschaftliches Zentrum (MZE), Karlsruhe Institute of Technology (KIT) Straße am Forum 7 76131 Karlsruhe Germany
Univ. Bordeaux, CNRS, Bordeaux INP/ENSCBP, Laboratoire de Chimie des Polymères Organiques, UMR 5629 16 Avenue Pey-Berland, F-33607 Pessac Cedex France
RSC Adv. 2018 Sep 7;8(55):31490-31495. doi: 10.1039/c8ra07150k. eCollection 2018 Sep 5.
We introduce a novel isocyanide-based multicomponent reaction, the Passerini four component reaction (P-4CR), by replacing the carboxylic acid component of a conventional Passerini three component reaction (P-3CR) with an alcohol and CO. Key to this approach is the use of a switchable solvent system, allowing the synthesis of a variety of α-carbonate-amides. The reaction was first investigated and optimized using butanol, isobutyraldehyde, -butyl isocyanide and CO. Parameters investigated included the effect of reactant equivalents, reactant concentration, solvent, catalyst, catalyst concentration and CO pressure. Of the other parameters, the purity of the aldehyde and its tendency to oxidize was one of the most critical parameters for a successful P-4CR. After optimization, a total of twelve (12) P-4CR compounds were synthesized with conversions ranging between 16 and 82% and isolated yields between 18 and 43%. Their structures were confirmed H and C NMR, FT-IR and high resolution mass spectrometry (ESI-MS). In addition, three (3) hydrolysis products of P-4CR (α-hydroxyl-amides) were successfully isolated with yields between 23 and 63% and fully characterized (H, C NMR, FT-IR and ESI-MS) as well.
我们介绍了一种新型的基于异腈的多组分反应，即帕瑟里尼四组分反应（P-4CR），该反应通过用醇和一氧化碳取代传统帕瑟里尼三组分反应（P-3CR）中的羧酸组分来实现。这种方法的关键在于使用可切换的溶剂体系，从而能够合成多种α-碳酸酯-酰胺。该反应首先使用丁醇、异丁醛、异丁基异腈和一氧化碳进行研究和优化。研究的参数包括反应物当量、反应物浓度、溶剂、催化剂、催化剂浓度和一氧化碳压力。在其他参数中，醛的纯度及其氧化倾向是成功进行P-4CR的最关键参数之一。优化后，共合成了十二种（12）P-4CR化合物，转化率在16%至82%之间，分离产率在18%至43%之间。通过氢谱和碳谱核磁共振、傅里叶变换红外光谱和高分辨率质谱（电喷雾电离质谱，ESI-MS）对其结构进行了确认。此外，还成功分离出了三种（3）P-4CR的水解产物（α-羟基酰胺），产率在23%至63%之间，并对其进行了全面表征（氢谱、碳谱核磁共振、傅里叶变换红外光谱和电喷雾电离质谱）。
