Open-Air Dual-Diamination of Aromatic Aldehydes: Direct Synthesis of Azolo-Fused 1,3,5-Triazines Facilitated by Ammonium Iodide

A new and practical protocol for the synthesis of medicinally privileged azolo[1,3,5]triazines by simply heating under air has been presented. The in situ generated N-azolo amidines from commercially available aromatic aldehydes and 3-aminoazoles with ammonium iodide undergo the second diamination to accomplish the [3 + 1 + 1 + 1] heteroannulation reaction. This convenient process is appreciated by high efficiency, broad substrate scope, gram-scale synthesis, and operational simplicity under reagent-free conditions.

Automated summary

A new and practical protocol has been developed for the synthesis of medicinally privileged azolo[1,3,5]triazines by simply heating under air. The method involves in situ generation of N-azolo amidines from commercially available aromatic aldehydes and 3-aminoazoles with ammonium iodide, followed by a second diamination to accomplish the heteroannulation reaction. This process is appreciated for its high efficiency, broad substrate scope, gram-scale synthesis, and operational simplicity under reagent-free conditions.