This methodology demonstrates synthesis of 1,2,4,5-tetrazines in 15 minutes, suggesting advantages for medicinal chemistry applications.
A rapid and effective method for the preparation of 3,6-disubstituted-1,2,4,5-tetrazines from N-tosylhydrazones has been developed using phenyliodine(III) diacetate as an oxidant and cesium carbonate (Cs₂CO₃) as a base. The reaction completes in a single step under transition-metal-free conditions through an oxidative C–N bond-formation approach. This developed method offers numerous advantages, including a short reaction time (15 min), operational simplicity, mild conditions, and moderate to high product yields. In general, this methodology offers a practical and useful approach for synthesizing 1,2,4,5-tetrazine scaffolds, which are highly valuable in both synthetic and medicinal chemistry.
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Singhal et al. (2025) studied this question.
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