Azides safely used to synthesize diamines

Academic researchers often develop organic synthesis methods that offer efficient new routes to industrially important chemicals. But many of these methods are considered untouchable in an industry setting because they involve hazardous reagents that can’t be safely handled on a larger scale or because they are cost prohibitive to implement. Sometimes, though, a success story does come along.

An industry-academic collaboration led by Hao Xu of Georgia State University and Marino Nebuloni of Italian specialty chemical company Redox Laboratory has developed a gram-scale procedure for directly adding azides to olefins to make vicinal primary diamines (Org. Process Res. Dev. 2017, DOI: 10.1021/acs.oprd.7b00312).

Xu’s group first reported the mild-mannered method in late 2015, converting unfunctionalized linear and cyclic olefins to diamines at room temperature using trimethylsilyl azide, a benziodoxole oxidizing reagent, and an iron catalyst with a tridentate ligand (Angew. Chem. Int. Ed. 2015, DOI: 10.1002/anie.201507550). The reaction drew the attention of industrial chemists as a general approach for producing diamines, Xu tells C&EN. This interest led to the trans-Atlantic partnership to explore the possibility of large-scale applications.

The collaboration with Redox Laboratory involved a safety assessment of the reagents, diazide intermediates, and product diaminium salts. The assessment revealed that the most problematic compounds, the diazide intermediates, are thermally stable but moderately shock-sensitive, and that the diaminium salts made from them are more stable. Guided by that knowledge, the team optimized the procedure to develop a gram-scale reaction to produce diaminium salts directly without having to purify the diazides.