Carboxamides transamidation

Enzyme-mediated chemistry can also inspire the development of novel nonenzymafic catalysts. Stahl, Gellman and collaborators at Wisconsin have taken on the challenge of developing transamidation catalysts, successfully identifying Al(III) complexes capable of equihbrafing mixtures of tertiary carboxamides with secondary amines [66,67]. For example, treatment of an equimolar mixture of 44 and 45 with 2.5 mol% of an aluminum catalyst in... 

The transamidation mechanism starts with the nucleophilic attack by the thiol group of an active-site cysteine residue (the catalyhc triad is composed of Cys-276, His-334, and Asp-358) on the donor substrate y-carboxamide group, leading to loss of an equivalent of ammonia and formahon of a covalent thiolester intermediate. The acyl group of the transient thiolester is transferred to the acceptor amine substrate in the second step [45]. 

Many patents cover synthetic routes to anti-inflammatory compounds such as 20, 25, or 29. The transformations shown in Scheme 1 are included in process patents.25-29 Transamidation of certain 3-carboxanilides (32) produces novel N-substituted carboxamides of 4-hydroxy-2H-l,2-benzo-thiazine 1,1-dioxides (25) (Eq. 7).30... 

The terminal nitrogen of the 2-hydrazinocarbonyl in 2-(hydrazinocarbonyl)-7V-phenylpyridine-3-carboxamide undergoes intramolecular transamidation by acylation at 200 °C by the 3-carboxamide group to give l.33... 

The NH2 group of carboxamides, particularly if unsubstituted, can be exchanged for residues from other amines, hydrazines, etc. Thus A-formyl-amines are often obtained quite smoothly by heating the amine with form-amide in a vacuum at as low as 70°.1144 Higher carboxamides react analogously at temperatures of 150-200°.1145 Transamidation occurs more readily if the carboxamide is melted with the amine hydrochloride 692,1146 and diacyl-amides, including cyclic dicarboximides such as succinimide and phthalimide are more reactive than simple carboxamides.1147... 

---