Click chemistry-based strategies for the synthesis of 2-amino-alkyl-1,2,3-triazole-1,4-naphthoquinone derivatives make it possible to obtain desired products from 1,4-naphthoquinone (1,4-NQ), and bio-based lawsone, nor-lapachol and lapachol. The first route (Strategy A) starting from 1,4-NQ and amino alcohols, then 2-amino-alkyl-1,4-NQ alcohols, were tosylated. The azide ion displaced the tosylate group to afford 2-azide-alkyl-1,4-NQ, which was submitted to a copper-catalyzed azide alkyne cycloaddition (CuAAC) condition. The triazole-naphthoquinones were obtained in an overall yield of roughly 47%. Another pathway (Strategy B) substituted bromo-alkyl-phthalimides using NaN3 as the nucleophile, sequential CuAAC and deprotection of phthalimide group with hydrazine producing amino-triazoles. The subsequent reaction with 1,4-NQ produced 2-amino-alkyl-1,2,3-triazole-1,4-NQ derivatives in an overall yield of 45-76% in four steps. After we developed these two strategies, linear synthesis (Strategy A) was chosen to prepare 2-[(2-(1H-1,2,3-triazol-1-yl)ethylamino)]-3-(3-methylpropenyl)-1,4-naphthoquinones from lawsone with an overall yield of approximately 27% in six steps. On the other hand, convergent synthesis (Strategy B) was employed for the synthesis of 2-[(4-phenyl-1H-1,2,3-triazol-1-yl)alkyl-amino)]-3-(3-methylbut-2-en-1-yl)-1,4-naphthoquinones from the reaction between 2-methoxy-lapachol with amino-triazoles with a global yield of about 21%. These synthetic strategies might lead us to new opportunities to build small-molecule libraries for future biological exploration.

Fifteen naphthoquinones, sixteen phenazines and fifteen aryl triazoles were synthesized and evaluated against Mycobacterium tuberculosis. Twenty five substances are reported here for the first time and, among all of the compounds evaluated, six presented MIC (minimal inhibitory concentration) values < 6.25 µg mL-1. These substances are promising antimycobacterial prototypes.

A convenient, efficient and fast acetylation combining clays and ultrasound irradiation is described. Some molecules from nature or synthetic source, i.e., D-glucose, glycerol, D-mannitol and 1,2,3-triazolic derivatives such as N-glucosyl sugars and 2-substituted 1,4-naphthoquinone structures were acetylated. This kind of chemistry may be classified as eco-friendly because the reactions take a short time and the catalyst is reusable.

Uma série de derivados 1,2,3-triazólicos foi sintetizada a partir de N-alquilftalimida-azidas (A1 -A4) e alcinos (a-e) sob irradiação de ultrassom na presença de CuI, Et3N e DMF como solvente. O presente protocolo forneceu 18 novos 1,2,3-triazóis (1-4) em rendimentos de bons a excelentes (67-98%).

A series of 1,2,3-triazole derivatives was synthesized from N-phthalimidoalkyl-azides (A1 -A4) and alkynes (a-e) under ultrasound irradiation in the presence of CuI, Et3N and DMF as solvent. The present protocol afforded 18 new 1,2,3-triazoles (1-4) in good-to-excellent yields (67-98%).