Explorando as condições reacionais de reações de Groebke-Blackburn-Bienaymé aplicada à síntese de imidazo[2,1-b]tiazois
Data
2021-07-16
Autores
Fiorentino, Everton Silva de Castro [UNIFESP]
Orientadores
Longo Junior, Luiz Sidney [UNIFESP]
Tipo
Trabalho de conclusão de curso de graduação
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Nas últimas duas décadas, a reação multicomponente de Groebke-Blackburn-Bienaymé (GBB) tem sido estudada como uma ferramenta importante para a síntese de compostos heterocíclicos nitrogenados, tais como as imidazo[1,2-a]piridinas e os imidazo[2,1-b]tiazóis, os quais possuem potenciais atividades biológicas. Estas reações acontecem quando uma amidina, um aldeído e uma isonitrila reagem entre si, geralmente sob catálise ácida. Esse trabalho visou o estudo metodológico da reação de GBB catalisada por triflatos de terras raras – RE(OTf)3, RE = Sc, La, Gd, Yb – como ácido de Lewis, para a obtenção de imidazo[2,1-b]tiazóis, assim como a exploração de diversas outras condições reacionais, visando a melhoria do rendimento da reação. Para esse estudo, uma reação modelo foi estabelecida, utilizando benzaldeído, terc-butil-isonitrila e 2-aminotiazol para obtenção da N-terc-butil-6-fenil-imidazo[2,1-b]tiazol-5-amina de interesse, a qual pôde ser obtida em rendimentos variados (38-60%), a depender do catalisador, do solvente a das condições utilizadas. O imidazo[2,1-b]tiazol obtido foi devidamente caracterizado por ressonância magnética nuclear (RMN) de 1H e 13C. Por fim, o presente trabalho complementa um estudo iniciado anteriormente pelo nosso grupo de pesquisa, e dessa forma, permitiu concluir que as reações GBB que utilizaram 2-aminopiridina como componente amidina da reação foram mais eficientes, comparadas àquelas reações com 2-aminotiazol, uma amidina menos nucleofílica.
In the last two decades, the Groebke-Blackburn-Bienaymé (GBB) multicomponent reaction has been studied as an important tool to acess different nitrogen-based heterocycles such as imidazo[1,2-a]pyridines and imidazo[2, 1-b]thiazoles, which have potential biological activities. These reactions happen when an amidine, an aldehyde and an isonitrile react with each other, usually under acid catalysis. This work aimed at the methodological study of the reaction of the GBB reaction catalyzed by rare earth triflates - RE(OTf)3, RE = Sc, La , Gd, Yb – as Lewis acid, to obtain imidazo[2,1- b]thiazoles, as well as the exploration of several other reaction conditions, aiming at improving the reaction yield. For this study, a model reaction was established, using benzaldehyde, tert-butyl-isocyanide and 2-aminothiazole to obtain the N-tert-butyl-6- phenyl-imidazo[2,1-b]thiazol-5-amine of interest , which could be obtained in varied yields (38-60%), depending on the catalyst, the solvent and the conditions used. The imidazo[2,1-b]thiazole obtained was duly characterized by nuclear magnetic resonance (NMR) of 1H and 13C. Finally, the present work complements a study previously started by our research group, and thus, allowed us to conclude that the GBB reactions that used 2-aminopyridine as the amidine component of the reaction were more efficient, compared to those reactions with 2-aminothiazole, a less nucleophilic amidine.
In the last two decades, the Groebke-Blackburn-Bienaymé (GBB) multicomponent reaction has been studied as an important tool to acess different nitrogen-based heterocycles such as imidazo[1,2-a]pyridines and imidazo[2, 1-b]thiazoles, which have potential biological activities. These reactions happen when an amidine, an aldehyde and an isonitrile react with each other, usually under acid catalysis. This work aimed at the methodological study of the reaction of the GBB reaction catalyzed by rare earth triflates - RE(OTf)3, RE = Sc, La , Gd, Yb – as Lewis acid, to obtain imidazo[2,1- b]thiazoles, as well as the exploration of several other reaction conditions, aiming at improving the reaction yield. For this study, a model reaction was established, using benzaldehyde, tert-butyl-isocyanide and 2-aminothiazole to obtain the N-tert-butyl-6- phenyl-imidazo[2,1-b]thiazol-5-amine of interest , which could be obtained in varied yields (38-60%), depending on the catalyst, the solvent and the conditions used. The imidazo[2,1-b]thiazole obtained was duly characterized by nuclear magnetic resonance (NMR) of 1H and 13C. Finally, the present work complements a study previously started by our research group, and thus, allowed us to conclude that the GBB reactions that used 2-aminopyridine as the amidine component of the reaction were more efficient, compared to those reactions with 2-aminothiazole, a less nucleophilic amidine.