The Forgotten Pyrazines: Exploring the Dakin-West Reaction

Chemistry. 2020 Jun 26;26(36):8090-8100. doi: 10.1002/chem.202000475. Epub 2020 Jun 5.

Abstract

Pyrazines are an underreported class of N-heterocycles available from nitrogen-rich biomass presenting an interesting functional alternative for current aromatics. In this work, access to pyrazines obtained from amino acids by using the 90 year old Dakin-West reaction was explored. After a qualitative screening several functional proteinogenic amino acids proved good substrates for this reaction, which were successfully scaled to multigram scale synthesis of the corresponding intermediate α-acetamido ketones. Subsequently, the conditions towards pyrazine formation using δ-amino-levulinic acid were optimized, and these were employed to synthesize a relevant set of five functional dimethylpyrazines in high purity. These pyrazines can be considered a versatile toolbox of aromatic building blocks for a wide range of applications, such as in the synthesis of polymers or metal-organic frameworks.

Keywords: amino acids; biobased building blocks; nitrogen heterocycles; radical ions; synthetic methods.

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