Boric Acid: A Highly Efficient Catalyst for Transamidation of Carboxamides with Amines

Abstract

A novel method of transamidation of carboxamides with amines using catalytic amounts of readily available boric acid under solvent-free conditions has been developed. The scope of the methodology has been demonstrated with (i) primary, secondary, and tertiary amides and phthalimide and (ii) aliphatic, aromatic, cyclic, acyclic, primary, and secondary amines.

Direct Synthesis of Amides from Carboxylic Acids and Amines Using B(OCH2CF3)3

“…40 All of these methods require high temperatures, anhydrous conditions and purification by column chromatography. The direct transamidation of DMF has recently been achieved with boric acid, 35 PhI(OAc) 2 , 34 l -proline, 37 and imidazole, 41 but at high temperatures, 34,35 with extended reaction times, 34,35,41 and/or with purification by column chromatography. 41 We therefore anticipated that B(OCH 2 CF 3 ) 3 -mediated transamidation of DMF may provide a useful formylation method, especially if the products could be readily purified by solid phase workup.…”

An improved solvent-free synthesis of flunixin and 2-(arylamino) nicotinic acid derivatives using boric acid as catalyst

“…Boric acid [H 3 BO 3 or B(OH) 3 ] has attracted particular attention in recent years as catalyst in organic synthesis [22–25], because of many advantages such as uncomplicated handling, inexpensiveness, eco-friendly nature and commercially available [26]. Consequently, we have considered the synthesis of 2-(2-methyl-3-trifluoromethylanilino)nicotinic acid ( 3a ), in the presence of boric acid under solvent-free conditions, and its salt, flunixin meglumine ( 6 ) under reflux in EtOH (Scheme 1).…”

Transamidation of primary amides with amines catalyzed by zirconocene dichloride

“…Longer reaction times were required for less reactive amides such as benzamide and related aromatic amides (Table 1, entries 4-7). N-Boc prolinamide 10 ( Table 1, entry 8) was found to be less reactive, perhaps due to its chelating ability, but we were pleased to see that stereochemistry was fully retained in the secondary amide product. A range of other amines was used successfully (Table 2).…”

“…5 Analysis of the 1 H NMR spectra of Cp 2 ZrCl 2 in the presence of varying concentrations of either benzamide or benzylamine revealed that the cyclopentadienyl ligands were not displaced and that both substrates bound fairly weakly (K a = 0.4 M -1 for benzylamine and 1.5 M -1 for benzamide). 10 A kinetic analysis of the reaction established that the reaction was first order in both Cp 2 ZrCl 2 and benzamide. However, the reaction was found to be second order in benzylamine.…”