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

Direct access to alkyl-substituted pyrazine N-oxides has been accomplished through an intermolecular dehydrogenative cross-coupling reaction of ethers and pyrazine N-oxides in the presence of tert-butyl hydroperoxide (TBHP). This approach successfully provided a variety of alkyl-substituted pyrazine N-oxides in up to 96% yield. Thermogravimetric analysis indicates that the degradation temperature of C2-alkyated product 3a is approximately 263 degrees C. Under pyrolysis conditions, 3a generated several compounds such 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.