Oxidative Amidation of Methylarenes and Heteroamines under Metal‐Free Conditions

Abstract

Synthesis of heteroamides through oxidative amidation of methylarenes with hetero aromatic amines using tert‐Butyl hydroperoxide (TBHP) as oxidant has been described. The present method represents a significant development for the oxidative amidation of methylarenes to obtain heteroamides which does not require metal catalyst and TBHP act as only oxidant. Methylarenes are easy to handle, stable, commercially available (by‐products in gasoline industry) and used as carbonyl source for amide synthesis. The reaction proceeds through the imine intermediate formation and its subsequent oxidation by TBHP provides the desired amides.

Chemodivergent synthesis of N-(pyridin-2-yl)amides and 3-bromoimidazo[1,2-a]pyridines from α-bromoketones and 2-aminopyridines

“…Based on the above results and previous knowledge, we proposed a plausible mechanism for this chemodivergent reaction. 22 As shown in Scheme 6, the reaction proceeded via the initial displacement of the halogen atom by the pyridine ring nitrogen to afford pyridinium salt (8), which subjected a facile closure and provided the shared intermediate 5aa. In protocol A, t-BuOc, which was generated in I 2 /TBHP system, 23 attacked the double bond of 5aa to afford 9, 9 subsequently transferred to 11.…”

“…7 Adimurthy's group synthesized N-(pyridin-2yl)amides via oxidative amidation of methylarenes using TBHP in decane. 8 Recently, two elegant works on Cu-catalyzed aerobic oxidative C-C bond cleavage for the preparation of N-(pyridin-2yl)amide had been developed. Hwang et al reported a visiblelight-promoted aerobic oxidative C-N coupling between 2-aminopyridine and terminal alkynes through C^C triple bond cleavage (Scheme 1b).…”

Recent Advances in the Functionalization of Hydrocarbons: Synthesis of Amides and its Derivatives

“…Pappula et al. reported an efficient TBHP‐mediated oxidative amidation of methylarenes with heteroaromatic amines, which proceeded under metal‐ and additive‐free conditions (Scheme a) . The resulting N ‐pyridyl benzamides ( 4 ) are useful building blocks for the synthesis of 2‐pyridyl urea derivatives, which exhibit various biological activities –.…”

Graphene oxide‐catalyzed CSp3–H activation of methylarenes in aqueous medium: A unified metal‐free access to amides and benzimidazoles

“…Additionally, non‐reusability of the catalytic system explains the ineffectiveness of these protocols for industrial application. In spite of subtle improvements of the reaction conditions, somewhere down the line these reactions still lack versatility.…”