Department of Chemistry and Biochemistry, Florida State University , Tallahassee, Florida 32306, United States , and Department of Chemistry, Department of Chemical and Life Science Engineering, Virginia Commonwealth University , Richmond, Virginia 23284, United States.
Org Lett. 2013 Oct 18;15(20):5298-301. doi: 10.1021/ol4025265. Epub 2013 Oct 4.
Pyridines with 2,3,4 and/or 5 substitution remain challenging to prepare. Existing strategies to form multisubstituted 2-halonicotinonitriles via enamines suffer from dimerization of the starting alkylidene malononitriles resulting in low yields. Through alteration of reaction conditions, a new high yielding method into enamines was realized by condensing DMF-DMA and alkylidene malononitriles in the presence of substoichiometric acetic anhydride. Cyclization of the resulting enamines under Pinner conditions provided 2-halonicotinonitriles in high overall yields.
带有 2、3、4 和/或 5 取代基的吡啶仍然难以制备。现有的通过烯胺形成多取代 2-卤代烟腈的策略受到起始亚甲基丙二腈二聚的影响，导致产率低。通过改变反应条件，在亚化学计量的乙酸酐存在下，用 DMF-DMA 和亚甲基丙二腈缩合，实现了一种新的高产率烯胺合成方法。在 Pinner 条件下，所得烯胺的环化以高总收率提供 2-卤代烟腈。
