44ª Reunião Anual Virtual da SBQ

Heterocyclic compounds containing the 1,2,3-triazole nucleus have received special attention in the field of synthetic chemistry since there are many possibilities of application as starting materials and in biological and material areas, like antimicrobial1 and antibacterial action2. In this scenario, the objective of this work is the synthesis of 4-functionalized 1,2,3 triazolic amines and carboxylic acids with novel structures.
The amines (5) were obtained through a four-step linear synthesis and 1,2,3-triazole 4-carboxylic acids (6) in three-step linear synthesis (Scheme 1). Firstly, functionalized anilines (1) underwent a diazotization reaction in the presence of sodium nitrite (NaNO2), hydrochloric acid (HCl) and sodium azide (NaN3) at 0 °C to generate the corresponding azides (2)3 in 96% yield. Then, the azides and the propargyl alcohol reacted in a Copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction to build exclusively the 1,4-disubstituted 1,2,3-triazole ring with a primary alcohol (3) in tert-butanol and water at room temperature4 in 85% yield. The aldehydes were obtained through partial oxidation of primary alcohols (4) by adding IBX in dimethylsulfoxide (DMSO) at room temperature5, with 95% yield. Then, the amines were obtained by reductive amination of aldehydes (5) in presence of ammonium hydroxide (NH4OH) with Zinc-Modified Cyanoborohydride, prepared mixing sodium cyanoborohydride (NaBH3CN) and anhydrous zinc chloride (ZnCl2), in methanol6 (25%). In parallel, the triazole alcohol was completely oxidated to corresponding carboxylic acids with 90% yield, using KMnO4 in tert-butanol and water at room temperature7.
Therefore, the molecules were obtained in excellent yields and with classical and reproducible synthetic methodologies. As a perspective, the final products will be sent for biological testing to assess the potential antimicrobial action.
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1. Sheremet, EA. Russ. J. Org. Chem. 2004;40(4):594–595.
2. Vatmurge, NS. Org. Biomol. Chem. 2008;6(20):3823.
3. Barral, K. Org. Lett. 2007;9(9)1809–1811.
4. Sharpless, KB. Angew. Chem., Int. Ed. 2001;40(11):2004-2021.
5. Frigerio, M. Org. Chem., 1995;60(22);7272-7276.
6. Kim, S. J. Org. Chem. 1985;50(11):1927–1932.
7. Abiko, A. Tetrahedron letters. 1986;27(38):4537-4540.