Direct Formation of Amides from Carboxylic Acids and Amines Catalyzed by Niobium(V) Oxalate Hydrate

Abstract

A wide range of metal salts and oxides were screened to test the catalytic effect in the formation of amides. A watercompatible catalyst, Niobium(V) oxalate hydrate, proved the ability to catalyze the direct formation of amides from carboxylic acids and amines with a low catalyst loading of 1% in a 1:1 ratio of acids and amines, with the water removal through azeotropic distillation of toluene/water mixtures, which showed a good atomic economic efficiency. Both aromatic and aliphatic carboxylic acids worked well with primary aliphatic amines in the reaction, however, aniline, as an example of primary aromatic amines, needed more than one equivalent amount to complete the amide formation.

Large-Scale Amidations in Process Chemistry: Practical Considerations for Reagent Selection and Reaction Execution

“…However, Lewis acids have found wide application in numerous transformations in organic chemistry, and amide bond formation is no exception. Thus, Zr, Ti, Nb, Hf, Ni, Ta, and Fe Lewis acids have been shown to catalyze direct amide bond formation, in some cases under very mild conditions, such as 25 °C for Hf, but as in the case of boron-derived catalysts, with relatively simple substrates. Considering the vast number of commercially available Lewis acids, it is likely that many others will eventually be discovered to provide this same function and applied to more complex substrates.…”

Recent developments in catalytic amide bond formation

“…[87] The authors suggest an interesting mechanism involving co-catalysis with isothiazolones coating the surface of the nanoparticles. Group V metals catalysts, such as Nb 2 O 5 [91,99,100] and Ta(OMe) 5 [94] have also been applied to direct amidation of carboxylic acids and have desirable features, such as high yields with a wide substrate scope, water tolerance and ability to couple β-amino acids through bidentate substrate chelation after initial in-situ generation of a silyl ester from the corresponding carboxylic acid and TMS-Imidazole ( Figure 10). [94] While the niobium catalysts required highly elevated temperatures (refluxing toluene) the tantalum catalyst could operate near room temperature although its use is complicated by significantly higher cost and scarcity.…”

Separation of Lactic Acid Based on Amide-Based Hydrophobic Deep Eutectic Solvents: Insights from Experiments and Molecular Dynamics Simulations

“…28 The amide bond is an essential and intriguing structure present in many crucial compounds, such as natural products and pharmaceuticals. 28,29 The low toxicity of amides has been confirmed via the modeling method and the experimental method by researchers. 30,31 Amides have the ability to form hydrogen bonds, are biodegradable, and have low toxicity.…”

“…Amide structures have been extensively studied in the field of biological proteins and natural peptides . The amide bond is an essential and intriguing structure present in many crucial compounds, such as natural products and pharmaceuticals. , The low toxicity of amides has been confirmed via the modeling method and the experimental method by researchers. , Amides have the ability to form hydrogen bonds, are biodegradable, and have low toxicity. Therefore, amides are more environmentally friendly than phosphorus groups …”