We report a simple, fast, and eco-friendly solvent-free protocol for the synthesis of 2-aminothiazoles and 2-amino-1,3-selenazoles (16 examples) through Hantzsch condensation without the use of a catalyst. It is noteworthy that this type of procedure is unprecedented for the synthesis of 1,3-selenazoles. Reactions proceed to completion in a few seconds and products are obtained in moderate to excellent yields after easy workup. Moreover, the synthesis of 4-(2-amino-1,3selenazol-4-yl)benzonitrile hydrobromide is reported for the first time.

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A very fast method for the synthesis of the title thiazoles and selenazoles through Hantzsch cyclization starting from thiourea and selenurea, resp., is developed.

Tuberculosis (TB), remains a global health challenge, despite the many efforts and recent advances in medicine and pharmacology. The World Health Organization estimates that 1.5 million people worldwide died due to TB infection in 2018. In this context, the search for novel molecules that can offer higher potency, shorter treatment times, and fewer side effects is urgent. This work describes the synthesis of eight new benzylpiperazines containing the pyrazine moiety, with potential activity against TB. The structures were rationally planned using the molecular hybridization technique, from the drug pyrazinamide and the benzylpiperazine core. All proposed substances were obtained from a simple and reproductible synthetic process, in low yields.

NERY, A. C. S.; AVELLAR, M. M.; GOMES, C. R. B.; DE SOUZA, M. V. N.; VASCONCELOS, T. R. A.; Curr. Org. Synth. 12 (2015) 2, 140-149, http://dx.doi.org/10.2174/1570179411666141201201009 ; Inst. Tecnol. Farm.-Far Manguinhos, FioCruz-Fundacao Oswaldo Cruz, 21041 Rio de Janeiro, Brazil; Eng.) -S. Adam 30-287

Background: 2-aminoselenazoles became an important core in medicinal chemistry after the discovery of Ebselen and Ethaselen. Therefore, many researchers have reported the synthesis of small selenazole intermediates via Hantzsch cyclization using a wide array of methodologies and catalysts. Methods:In this work, we investigated the formation of 2-aminoselenazoles on various organic solvents and in water, under catalyst-free conditions. Moreover, these molecules and their 2-aminothiazoles analogues were assessed in vitro for their antitubercular activity against Mycobacterium tuberculosis and the results compared.Results: Instant reactions were observed when using polar aprotic solvents and all selenazoles were synthesized in water using sonochemistry. Furthermore, two selenazoles and one thiazole displayed activity in the µM range and the selenium heterocycles seems to be more potent than their sulphur analogues. Conclusion:This is the first study of selenazoles against M. tuberculosis. It is noteworthy that 2-amino-1,3-selenazoles are interesting synthetic intermediates that could be incorporated into novel prototypes against tuberculosis.