33986-97-9

Upstream product

• 530-44-9 4-(Dimethylamino)benzophenone 
• 99-98-9 4-amino-N,N-dimethylaniline 
• 698-70-4 4-Iodo-N,N-dimethylaniline 
• 55-21-0 benzamide 
• 1934-92-5 N-methyl-N-phenyl-benzamide 
• 93-98-1 N-phenyl benzoyl amide 
• 2998-94-9 4-dimethylamino-benzophenone-seqtrans-oxime 

Relevant academic research and scientific papers

Switching from biaryl formation to amidation with convoluted polymeric nickel catalysis

A stable, reusable, and insoluble poly(4-vinyl-pyridine) nickel catalyst (P4VP-NiCl2) was prepared through the molecular convolution of poly(4-vinylpyridine) (P4VP) and nickel chloride. We proposed a coordination structure of the Ni center in the precatalyst based on elemental analysis and Ni K-edge XANES, and we confirmed that it is consistent with Ni K-edge EXAFS. The Suzuki?Miyaura-type coupling of aryl halides and arylboronic esters proceeded using P4VP-NiCl2 (0.1 mol % Ni) to give the corresponding biaryl compounds in up to 94% yield. Surprisingly, when the same reaction of aryl halides and arylboronic acid/ester was carried out in the presence of amides, the amidation proceeded predominantly to give the corresponding arylamides in up to 99% yield. In contrast, the reaction of aryl halides and amides in the absence of arylboronic acid/ester did not proceed. P4VP-NiCl2 successfully catalyzed the lactamization for preparing phenanthridinone. P4VP-NiCl2 was reused five times without significant loss of catalytic activity. Pharmaceuticals, natural products, and biologically active compounds were synthesized efficiently using P4VPNiCl2 catalysis. Nickel contamination in the prepared pharmaceutical compounds was not detected by ICP-MS analysis. The reaction was scaled to multigrams without any loss of chemical yield. Mechanistic studies for both Suzuki?Miyaura and amidation were performed.

Highly Chemoselective, Transition-Metal-Free Transamidation of Unactivated Amides and Direct Amidation of Alkyl Esters by N-C/O-C Cleavage

The amide bond is one of the most fundamental functional groups in chemistry and biology and plays a central role in numerous processes harnessed to streamline the synthesis of key pharmaceutical and industrial molecules. Although the synthesis of amides is one of the most frequently performed reactions by academic and industrial scientists, the direct transamidation of tertiary amides is challenging due to unfavorable kinetic and thermodynamic contributions of the process. Herein, we report the first general, mild, and highly chemoselective method for transamidation of unactivated tertiary amides by a direct acyl N-C bond cleavage with non-nucleophilic amines. This operationally simple method is performed in the absence of transition metals and operates under unusually mild reaction conditions. In this context, we further describe the direct amidation of abundant alkyl esters to afford amide bonds with exquisite selectivity by acyl C-O bond cleavage. The utility of this process is showcased by a broad scope of the method, including various sensitive functional groups, late-stage modification, and the synthesis of drug molecules (>80 examples). Remarkable selectivity toward different functional groups and within different amide and ester electrophiles that is not feasible using existing methods was observed. Extensive experimental and computational studies were conducted to provide insight into the mechanism and the origins of high selectivity. We further present a series of guidelines to predict the reactivity of amides and esters in the synthesis of valuable amide bonds by this user-friendly process. In light of the importance of the amide bond in organic synthesis and major practical advantages of this method, the study opens up new opportunities in the synthesis of pivotal amide bonds in a broad range of chemical contexts.

Nickel/Briphos-Catalyzed Direct Transamidation of Unactivated Secondary Amides Using Trimethylsilyl Chloride

Direct transamidation of secondary amides was developed via nickel catalysis. In the presence of trimethylsilyl chloride and manganese, Ni(diglyme)Cl2 with a Briphos ligand efficiently promoted the transamidation of N-aryl benzamide derivatives with primary amines to afford the corresponding secondary amides in moderate to good yields. Primary amines bearing electron-donating groups gave higher yields of the transamidation products.