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

Abstract

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.

Green Synthesis of Aromatic Nitrogen-Containing Heterocycles by Catalytic and Non-Traditional Activation Methods

“…Scheme 13 shows two examples of the synthesis of pharmaceutically relevant derivatives. The first example illustrates an open-air dual-diamination annulation to generate 5-aza-9-deazapurine derivatives ( Scheme 13 a) [ 128 ]. Commercially available aromatic aldehydes and aminoazoles afforded N -azolo amidines in the first step which then reacted with ammonium iodide to yield the corresponding fused triazines in good yield, up to 92%.…”