Synthesis of Arylamides via Ritter-Type Cleavage of Solid-Supported Aryltriazenes

Abstract

A novel route for the synthesis of N-arylamides via the cleavage of aryltriazenes with alkyl or aryl nitriles is presented. We developed a variation of the Ritter reaction that allows the use of acetonitrile as solvent and reagent in reactions with solid-supported precursors. The reaction was optimized for the generation of N-aryl acetamides using a diverse range of immobilized building blocks including o-, m-, and p-substituted aryltriazenes. The cleavage via the Ritter-type conversion was combined with an on-bead cross-coupling reaction of halogen-substituted aryltriazenes with pyrazoles. Additionally, the synthesis of on-bead generated arylboronic estersubstituted triazenes was shown. The developed procedure was further expanded to use other commercially available nitriles, such as acrylonitrile, benzonitrile, and chlorinated alkyl nitriles as suitable reagents for a Ritter-type cleavage of the prepared triazene linkers.

Transition Metal‐Catalyzed Reactions and Solid‐Phase Synthesis: A Convenient Blend

“…research group described the synthesis of biaryl acetamides using aryltriazenes as resin linkers. [50] In this way, immobilized boronic acid pinacol esters reacted with aryl halides to afford the corresponding biaryl compounds, that could be cleaved from the resin by a Ritter-type cleavage.…”

Recent Applications of Ritter Reactions in Organic Syntheses

“…In 2019, the new pathway was used for the synthesis of N ‐aryl amides 108 through the non‐classical Ritter reaction of nitrile 1 with immobilized triazenes 107 in the presence of HBF 4 ⋅ OEt 2 as catalyst (Scheme 45) The mechanism of the mention reaction is shown in Scheme 46 [54] …”

Nickel(II)- and Silver(I)-Catalyzed C–H Bond Halogenation of Anilides and Carbamates

“…During the optimization study we found that when silver acetate was used instead of NiCl 2 •6H 2 O, as the catalyst in the presence of MSA in toluene at 50 °C, the desired product was obtained in 53% yield (entry 16). We then optimized the reaction conditions further by using silver-based catalysts, and competitive results were obtained with 10 mol% of Ag 2 CO 3 in the presence of 3.0 equivalent of MSA (entries [16][17][18][19][20][21][22][23][24][25][26][27]. Unfortunately, the reaction was not successful in water as the solvent (see the Supporting Information for details).…”