Metal-Free Synthesis of 1,5-Disubstituted 1,2,3-Triazoles

Abstract

A three-component synthesis of 1,5-disubstituted 1,2,3-triazoles from α-acetyl-α-diazomethane sulfonamides, primary aliphatic amines, and aromatic aldehydes is presented. The 1,2,3-triazoles can be accessed in two alternative variants, depending on the substitutions in the sulfonamide portion of the diazo reagent. In one variant, intermediate 1,2,3-triazoline-4-sulfonamides are isolated chromatographically and then subjected to thermally promoted aromatization with elimination of sulfur­(IV) oxide and amine. In the other variant, both chemical transformations take place in a single step conducted at room temperature.

Novel Bis-Triazole Scaffold Accessed via Two Tandem [3+2] Cycloaddition Events Including an Uncatalyzed, Room-Temperature Azide-Alkyne Click Reaction

“…The reaction was allowed to go to completion in 48 h at room temperature whereupon the reaction mixture was absorbed on silica and subjected to column chromatography isolation of the product. To our sheer amazement, the product turned out to be not the initial adduct 4a but rather 9H-benzo [1,4]diazepine 5a, i. e. the product of the tandem three-component 1,2,3-triazole synthesis followed by intramolecular azide-alkyne click reaction which, apparently, proceeded at room temperature. Product 5a was isolated in respectable 78% yield; therefore, the reaction conditions were not further optimized (Scheme 1).…”

“…Likewise, heterocyclic azido aldehydes 3k-l failed to react with 1 and propargylamine (Figure 3). d] [1,4]diazepine (5) synthesis, we proceeded to look at the variations in the alkyne-containing amine component for this transformation. Introduction of -methyl substitution in propargylamine (compound 16) was tolerated and the respective reaction gave product 17 in the yield comparable to (and somewhat better than) that of unsubstituted compound 5a.…”

“…Recently, we reported a novel, metal-free synthesis of 1,5-disubstituted 1,2,3-triazoles via a three-component reaction of α-acetyl-α-diazomethane sulfonamide 1 with aldehydes and amines [4]. The reaction proceeded, presumably, through the formation of the initial 1,2,3-triazoline adduct 2 [5] which underwent aromatization with the loss of sulfur dioxide and N-Boc aniline.…”

1,2,3-Triazole Scaffold in Recent Medicinal Applications: Synthesis and Anticancer Potentials

“…18 Scheme 1. Synthesis of 1,2,3-triazole ring from azides and alkynes In addition, other methods for the synthesis of 1,2,3-triazoles were reported such as the reaction of vinyl bromides with aryl azides mediated by base (Scheme 2A), 19 the three-component reactions of a-acetyl-adiazomethane sulfonamides, primary aliphatic amines, and aromatic aldehydes (Scheme 2B), 20 the threecomponent reactions of a-CF3 carbonyl compounds, sodium azide, and amines mediated by DABCO (Scheme 2C), 21 the oxidative reaction of N-tosylhydrazones with anilines mediated by I2/TBPB (Scheme 2D), 22 and the three-component reactions of aldehydes, nitroalkanes, and organic azides (Scheme 2E) 23 as described in the literature. [24][25][26] Scheme 2.…”

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

“…Recently, we reported a novel, metal-free synthesis of 1,5disubstituted 1,2,3-triazoles via a three-component reaction of α-acetyl-α-diazomethanesulfonamide (1) with aldehydes and amines [4]. The reaction proceeded, presumably, through the formation of the initial 1,2,3-triazoline adduct 2 [5] which underwent aromatization with the loss of sulfur dioxide and N-Boc-aniline.…”