Estudos sobre a resolução cinética dinâmica de aminas benzílicas catalisadas por paládio suportado em dolomita
Data
2022-07-25
Autores
Arêas, José Carlos Queiroz [UNIFESP]
Orientadores
Siqueira, Fernanda Amaral de [UNIFESP]
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
As aminas quirais constituem uma da classe de compostos orgânicos importante, devido, principalmente devido à atividade biológica. São amplamente utilizadas nas indústrias químicas, agroquímicas e farmacêuticas devido à sua versatilidade. Sua aplicabilidade varia de auxiliar quiral à alvo biológico. Entretanto, devido à seletividade dos processos biológicos, o uso de aminas quirais enantiomericamente puras é importante.
Existem alguns métodos para sintetizar aminas enantiosseletivamente, dentre eles a resolução cinética dinâmica (RCD), que combina a resolução cinética enzimática com a racemização in situ do enantiômero remanescente. Esta metodologia tem ganhado cada vez mais atenção na área da síntese orgânica e apresenta como principal vantagem permitir a conversão total de uma mistura racêmica em um único enantiômero, em rendimento que pode chegar a 100%.
O presente trabalho descreve estudos sobre a reatividade de aminas quirais, frente a reações de RCD. Entre os compostos estudados, a 1-indanamina foi selecionada, pois apresenta em sua estrutura o esqueleto indânico, presente na molécula da rasagilina. Esta, por sua vez, constitui um medicamento usado para o tratamento da doença de Parkinson, comercializado pela Pfizer com o nome Azilect®.
Nas reações realizadas, foi usado o catalisador heterogêneo de paládio com suporte de dolomita, que foi desenvolvido em um trabalho do nosso grupo de pesquisa. Dentre suas várias vantagens, podem ser listadas a sua capacidade de reciclagem em até 5 vezes sem perda catalítica bem como a baixa quantidade de paládio ativo em sua composição.
Foram utilizados diferentes agentes acilantes, tempos reacionais e temperaturas, buscando obter as correspondentes acetamidas nos melhores valores de conversão, excesso enantiomérico e rendimento das reações possíveis.
Chiral amines are one important class of organic compounds, mainly because of their biological activity. They are widely applied in chemical, agrochemical and pharmaceutical industries, because of their versatility. Their usefulness ranges from chiral auxiliaries to biological target. However, due to the selectivity of biological processes, the use of enantiomerically pure amines is important. There are some methods for the enantioselective synthesis of amines, including dynamic kinetic resolution (DKR), which combines enzymatic kinetic resolution with in situ racemization. This methodology has received more attention in organic synthesis and has the advantage the possibility of 100% yield of only one enatiomer, starting from a racemic mixture. The present work describes studies on the reactivity of chiral amines against RCD reactions. Among the compounds studied, the 1- amine was selected because it has the indanic skeleton in its structure, present in the rasagiline molecule. This, in turn, is a drug used for the treatment of Parkinson's disease, marketed by Pfizer under the name Azilect®. In the reactions carried out, the heterogeneous palladium catalyst with dolomite support was used, which was developed in a work by our research group. Among its many advantages, its ability to recycle up to 5 times without catalytic loss can be listed, as well as the low amount of active palladium. Different acylating agents, reaction times and temperatures were used, seeking to obtain the corresponding acetamides at the best conversion values, enantiomeric excess and yields of the possible reactions.
Chiral amines are one important class of organic compounds, mainly because of their biological activity. They are widely applied in chemical, agrochemical and pharmaceutical industries, because of their versatility. Their usefulness ranges from chiral auxiliaries to biological target. However, due to the selectivity of biological processes, the use of enantiomerically pure amines is important. There are some methods for the enantioselective synthesis of amines, including dynamic kinetic resolution (DKR), which combines enzymatic kinetic resolution with in situ racemization. This methodology has received more attention in organic synthesis and has the advantage the possibility of 100% yield of only one enatiomer, starting from a racemic mixture. The present work describes studies on the reactivity of chiral amines against RCD reactions. Among the compounds studied, the 1- amine was selected because it has the indanic skeleton in its structure, present in the rasagiline molecule. This, in turn, is a drug used for the treatment of Parkinson's disease, marketed by Pfizer under the name Azilect®. In the reactions carried out, the heterogeneous palladium catalyst with dolomite support was used, which was developed in a work by our research group. Among its many advantages, its ability to recycle up to 5 times without catalytic loss can be listed, as well as the low amount of active palladium. Different acylating agents, reaction times and temperatures were used, seeking to obtain the corresponding acetamides at the best conversion values, enantiomeric excess and yields of the possible reactions.