Scalable and Safe Transformation of 3‑Hydroxypropionitrile to Its Amidoxime

• Published in: Organic process research & development 2022-01, Vol.26 (1), p.195-198
• Main Authors: Hlubb, Leah N, Johnson, Eric C, Sabatini, Jesse J, Orlicki, Joshua A
• Format: Article
• Language: English
• ISSN: 1083-6160; 1520-586X
• DOI: 10.1021/acs.oprd.1c00401

Scalable synthesis of amidoxime 1 by nucleophilic addition of 50% aq. NH2OH to 3-hydroxypropionitrile is reported. In the presence of hydroxyl and amidoxime moieties, this dually functional compound can be manipulated for the synthesis of heterocyclic compounds that may be useful for the energetic materials and pharmaceutical chemistry communities. In preparing 1, it was discovered that previously published procedures were either irreproducible and/or the processes were not practical on larger scales. Previously published procedures required flash chromatography and/or afforded the amidoxime product in a low yield. The improved method discussed in this paper involves rotary evaporation of the completed reaction mixture to remove excess water, followed by trituration in acetone to obtain 83–90% yields. This method has been carried out multiple times on the 86–94 g scale, with minimal exothermic activity detected.