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Updated: Dec 25, 2025

Synthesis of pH Dependent Pyrazole, Imidazole, and Isoindolone Dipyrrinone Fluorophores using a Claisen-Schmidt Condensation Approach
Published on: June 10, 2021
The Forgotten Pyrazines: Exploring the Dakin-West Reaction
Martien A Würdemann1, Cristina Niţu2, Stefaan M A De Wildeman1
1Aachen Maastricht Institute for Biobased Materials (AMIBM), Maastricht University, Urmonderbaan 22, 6167 RD, Geleen, The Netherlands.
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.
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