A journey into amide and alkylamine synthesis from CO

Overview & Synopsis

Nitrogen containing molecules are essential for life. They are also key products in the chemical industry and are produced at the megaton scale. Among these compounds, amides and alkylamines are of particular importance. Amides are indeed among the most ubiquitous functions in living systems and form important materials (nylon, hydrogels, etc.), solvents, or pharmaceutics. An analysis carried out by the three leading pharmaceutical companies in 2006, revealed that amide bonds formation was used in the synthesis of 65% of the drugs candidates. Classically, amide compounds are synthesized from the reaction of an activated carboxylic acid derivative with an amine but traditional methods prove expensive with a poor atom economy. An appealing alternative would consist in promoting the direct carbonylation of an amine with CO. During the last decade, a handful of catalysts were shown to facilitate the carbonylation of tertiary amines. However, they require harsh conditions (> 30 bar, > 190°C), and use of precious and/or toxic metal (palladium, rhodium or cobalt). In this context, we have designed the first system able to promote the carbonylation of amines to amides with iron catalysts. Low valent iron carbonyl complexes, in combination with a promotor (MeI) and a Lewis acid, favor the carbonylation of a variety of aromatic and aliphatic amines at low CO pressures (P < 8bar)