Construction of Tertiary Amides: Ni^II‐Catalyzed N‐Arylation of Secondary Acyclic Amides (2‐Picolinamides) with Aryl Halides

Abstract

Ni II -catalyzed CÀNc ross-coupling reactiono f secondary acyclic amides (2-picolinamides, which were derived from 2-picolinic acid and amines) and aryl halides for the construction of tertiary amides has been reported. Relatively inexpensive NiCl 2 was used as the catalystf or the N-arylation of various 2-picolinamides (secondary acyclic amides), in which the 2-picolinamide unit plausibly served as an internal ligand.Amidesa re important key functional groups in organic and medicinal chemistry,p harmaceuticals, drug discovery,a nd so forth. [1, 2] In particular, N-aryl amides [2] are prevalent motifs in biologically active natural products, synthetic and medicinally important molecules, peptides, and so forth. [1, 2] In general, various methods (e.g.,a cylation of amines or directa midation reactions using amines and carboxylic acids) have been developed to assemble amides, N-arylated amides in particular. [3, 4] Apart from the traditional methods, [3, 4] metal-catalyzed N-arylation of an amide system,c omprising the CÀNc ross coupling between an amide and as uitable coupling partner,h as received as pecial attention. [5][6][7][8] Since the discovery of the Goldberg reaction, [7a,b] remarkabled evelopments have been made to overcome the shortcomings of the Cu-based N-arylation/CÀ Nc oupling reaction of the amide system using various ligands. Notably,t he N-arylation was also achievedu sing Pd catalysts in the presence of ligands. [7, 8] There have been remarkable developments in the research topic pertainingt ot he N-arylation of cyclic and primary amides by the CÀNc ross-coupling strategy. [7][8][9] However,r eports dealing with the N-arylation of acyclics econdary amides by the CÀNc ross-couplings trategy are limited. [6][7][8][9] With regards to representative pioneering works on the N-arylation of acyclic secondary amides,B uchwald reported the N-arylation of acyclic secondary amides using the Cu catalyst/1,2-diamine ligand system [6a,b] and Pd catalyst/JackiePhos ligand system [8a] Asian

Amidation of Aryl Chlorides Using a Microwave-Assisted, Copper-Catalyzed Concurrent Tandem Catalytic Methodology

“…Initial development of such transformations using copper were first reported by Ullmann and Goldberg. , However, these reactions often required long reaction times, high temperatures, and, in some examples, the presence of copper in stoichiometric amounts. The development of nickel , and palladium − catalysts has led to the cross-coupling of aryl halides and amides under milder conditions. In addition to these methodologies, Buchwald , has developed effective copper-catalyzed amidations of aryl iodides and bromides using simple 1,2-diamines as ligands.…”

Copper-Catalyzed Coupling Reaction of (Hetero)Aryl Chlorides and Amides

“…The humbled nucleophilicity of amides (electron-withdrawing carbonyl groups) comparable to amines make them challenging partners in metal-catalyzed cross-coupling reactions. In recent decades, a number of Pd-, − Ni-, and Cu- − based catalytic systems have been successfully developed for this important transformation. Although less expensive and reactive (hetero)­aryl chlorides have been found to be workable under some Pd- and Ni-catalyzed coupling reactions with amides, − they are still problematic substrates when less expensive copper/ligand catalytic systems were used.…”

“…In recent decades, a number of Pd-, − Ni-, and Cu- − based catalytic systems have been successfully developed for this important transformation. Although less expensive and reactive (hetero)­aryl chlorides have been found to be workable under some Pd- and Ni-catalyzed coupling reactions with amides, − they are still problematic substrates when less expensive copper/ligand catalytic systems were used. In 2001, Buchwald and co-workers for the first time attempted amidation with aryl chlorides under the catalysis of CuI and 1,2-diamine ligands.…”

Development and validation of stability-indicating methods for determination of torsemide

“…TOR was determined by pharmacopoeial and non-pharmacopoeial methods where it is assayed in the British pharmacopoeia via non-aqueous titration [3], while assayed in the USP pharmacopoeia by HPLC method [4]. The non-pharmacopoeial methods used for determination of TOR include HPLC [5][6][7][8][9], LC/MS [10][11][12][13], GC/MS [14,15], spectrophotometry [16][17][18][19][20] and TLC-densitometry [21]. Stability-indicating HPTLC [22], HPLC [23] and ion selective electrode [24] methods have been recently reported for analysis of TOR but no spectrophotometric studies were performed.…”