An efficient and metal-free synthetic protocol for mono-, bis-, and spiro[1,2,4]triazolo[1,5-a]pyridines utilizing 1,2-diaminopyridine derivative via C–N bond formation

Abstract

An effective and direct synthetic strategy for a new series of functionalized mono-, bis-, and spiro[1,2,4]triazolo[1,5-a]pyridines from 1,2-diaminopyridine precursor has been described. Reaction of 1,2-diaminopyridine with ethyl orthoformate, acetic anhydride, maleic anhydride, carbon disulfide, or chloral hydrate under metal-free conditions afforded the desired triazolo[1,5-a]pyridine in good yield (62–76%). Furthermore, 1,2-diaminopyridine was converted to mono- and bis-[1,2,4]triazolo[1,5-a]pyridines via metal-free construction with decanoyl chloride, chloroacetyl chloride, terphthaloyl chloride, or diethyl succinate. Finally, spiro[[1,2,4]triazolo[1,5-a]pyridine and [1,2,4,3]triazaphospholo[1,5-a]pyridine derivatives were obtained via reaction of 1,2-diaminopyridine with cyclohexanone/pentanone in acetic acid or phosphorus pentasulfide in pyridine. This protocol aims to present some fundamental advances in the area of organic synthesis such as smart reaction conditions, improved yield, metal-free catalysts, no column purification, and no by-products, in addition to the broad functional scope.

Graphical Abstract

Keywords:

• C–N bond
• 1,2-diaminopyridine
• 4H-pyran
• metal-free synthesis
• triazolo[1,5-a]pyridine