Noncatalytic Approach for Amine Production

Sep 11th, 2017

Amines are crucially important for the production of many active pharmaceutical ingredients, functional materials and agrochemicals. Therefore, producers strongly require novel and effective technologies of nitrogen production.

A simple but efficient technology was designed at Rice University, Houston. The researchers believe that their new noncatalytic method is a more scalable and eco-friendly alternative to transition-metal-catalyzed cross-coupling way for the production of amines. As contrasted with the current approach, a novel technology is based on the formation of carbon-nitrogen bonds with the help of an umpolung or polarity-reversal reagent.

Being electronically and sterically derived, oximes and imines serve as a polarity-reversal reagent. The scientists have developed a single and double nitrogen umpolung the flexibility of which provides an efficient synthesis. As a result, they receive symmetrical and nonsymmetrical aryl alkyl-, diaryl-, and dialkyl amines.  Nitrogen-umpolung approach makes available those chemical routes which previously could be opened by means of expensive ligands and transition metals.

The approach is described in the Journal of the American Chemical Society by a group of chemists from Rice, who particularly mention the advantage of their method. After carbon-nitrogen bonds are made, long optimisation to produce nitrogen or even aryl-nitrogen is no longer required. The production can be performed at and below ordinary temperatures. Moreover, this method is cheap due to the commercial availability of aryl- and alkyl Grignard reagents.

A nitrogen-umpolung agent can convert primary amine to the Nitrogen-electrophilic imine. Thus, it opens up N-electrophilic space where different nucleophiles attack the electrophilic atom of nitrogen thus forming new carbon-nitrogen bonds.

The scientists note that they soon will be able to modulate the degree of N-electrophilicity. As a result, they will create new powerful Nitrogen-umpolung reagents. They anticipate the production of reagents on the multi-kilogram scales.  Overall, nitrogen bonds will likely be essential substrates in multiple different mechanical transformations.