Synthesis of Alkyl‐Substituted Pyrazine N‐Oxides by Transition‐Metal‐Free Oxidative Cross‐Coupling Reactions

Abstract

Direct access to alkyl-substituted pyrazine Noxides has been accomplished through an intermolecular dehydrogenative cross-couplingr eaction of ethers and pyrazine N-oxides in the presence of tert-butyl hydroperoxide (TBHP). This approach successfully provided av ariety of alkyl-substituted pyrazine N-oxides in up to 96 %y ield. Thermogravimetric analysis indicates that the degradation tem-perature of C2-alkyated product 3a is approximately 263 8C. Under pyrolysisc onditions, 3a generated several compoundss uch as 2,5-dimethylpyrazine, 2,3,5-trimethylpyrazine, and 3-ethyl-2,5-dimethylpyrazine, which are characterized by their distinct aromas. The results of the pyrolysis experiment support the use of these compounds as possible flavor additives.

Recent Progress in Non‐Catalytic C–H Functionalization of Heterocyclic N‐Oxides

“…In recent years, protocols for carrying out oxidative C-C coupling involving azine N-oxides and ethers without using transition metal compounds as catalysts have been developed (Scheme 60, Scheme 61). [97,98] The process is characterized by high selectivity.…”

Synthesis, odor characteristics and biological evaluation of N-substituted pyrrolyl chalcones

“…Here, we present the base-mediated transition metal free α-functionalization of N -substituted acetylpyrroles with commercial alcohols to generate N -substituted pyrrole and chalcone hybrids, based on the above reasons and our prior study on the synthesis of N -heteroaryl products (Scheme 1d). 18…”

Brønsted Acid-Catalyzed Minisci-Type Cross-Dehydrogenative Coupling of N-Heteroaromatics and Cyclic Ethers

“…After a careful survey of literature studies, we realized that the traditional functionalization of N -heteroaromatics in the presence of cyclic ethers generally suffers from external media, preactivated or functionalized substrates (usually nitrogen-atom-activated), or stoichiometric amounts of acid under metal-free conditions, which limit their widespread usage and contradict the principle of green chemistry. Thus, a convenient, efficient, and mild methodology for the direct alkylation of N -heteroaromatics is still attractive.…”