Direct Synthesis of 4-Aryl-1,2,3-triazoles via I₂-Promoted Cyclization under Metal- and Azide-Free Conditions

Abstract

We herein report an iodine-mediated formal [2 + 2 + 1] cyclization of methyl ketones, p-toluenesulfonyl hydrazines, and 1-aminopyridinium iodide for preparation of 4-aryl-NH-1,2,3-triazoles under metal-and azide-free conditions. Notably, this is achieved using p-toluenesulfonyl hydrazines and 1-aminopyridinium iodide as azide surrogates, providing a novel route toNH-1,2,3triazoles. Furthermore, this approach provides rapid and practical access to potent inhibitors of indoleamine 2,3-dioxygenase (IDO).

Copper-Catalyzed Azide–Alkyne Cycloaddition of Hydrazoic Acid Formed In Situ from Sodium Azide Affords 4-Monosubstituted-1,2,3-Triazoles

“…10 Current methods for the preparation of 4-substituted-1H-1,2,3-triazoles include acid-mediated cycloaddition of nitroolefins and sodium azide, 11 Pd or Cu-catalyzed reaction of bromoolefins, anti-2,3-dibromopropanoic acids, or acetylenes with sodium azide, 12 reactions of in situ formed propargyl azides via the Banert reaction, 13 multicomponent reactions of aldehydes, nitroalkanes, and sodium azide, 14 or enolizable ketones, ammonium acetate, and 1-azido-4-nitrobenzene, 15 Ndeallylation of allyltriazoles, 16 reactions of β-azolylenamines with sulfonyl azides, 17a and N,N-dimethyl enaminones and tosyl azide, 17b as well as iodine-promoted cyclization of arylmethyl ketones, p-toluenesulfonyl hydrazide, and 1-aminopyridinium iodide. 18 4-Substituted-1H-1,2,3-triazoles are also putative reaction products of cycloaddition between hydrogen azide (hydrazoic acid, HN 3 ) and terminal alkynes. hydrazoic acid and phenylacetylene proceeds sluggishly at elevated temperatures.…”

A Review on Molecular Iodine Catalyzed/Mediated Multicomponent Reactions

“…Huang et al [92] . reported an iodine‐promoted three‐component synthesis of 4‐aryl‐1H‐1,2,3‐triazoles 89 via [2+2+1] cyclization reaction between methyl ketones, p‐toulenesulphonyl hydazides and 1‐ aminopyridinum iodide in DMSO (Scheme 46).…”

“…Huang et al [92] reported an iodine-promoted three-component synthesis of 4-aryl-1H-1,2,3-triazoles 89 via [2 + 2 + 1] cyclization reaction between methyl ketones, p-toulenesulphonyl hydazides and 1-aminopyridinum iodide in DMSO (Scheme 46). This is noteworthy here that in this azide-free synthesis of 1,2,3-triazoles, azide was surrogated by the combination of p-toulenesulphonyl hydrazines and aminopyridinum iodide.…”

Emerging Trends in N‐Tosylhydrazone Mediated Transition‐Metal‐Free Reactions

“…Huang et al [75] . explored a reaction methodology to form 4‐aryl‐ NH ‐1,2,3‐triazoles 31 in iodine promoted [2+2+1] type cyclization reaction among methyl ketone 28 , N ‐tosylhydrazine 29 , and 1‐aminopyridinium iodide 30 .…”

“…Huang et al [75] explored a reaction methodology to form 4-aryl-NH-1,2,3-triazoles 31 in iodine promoted [2 + 2 + 1] type cyclization reaction among methyl ketone 28, N-tosylhydrazine 29, and 1-aminopyridinium iodide 30. This transformation proceeds in a single step and a metal-free, azide-free condition giving high to moderate yield.…”