Estudos visando a síntese de iminas quirais precursoras de indanonas via Ativação C(sp3)-H
Data
2022-10-26
Autores
Nakayama, Natália Lumi 
Orientadores
Craveiro, Marcus Vinicius
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Neste trabalho foram realizados estudos visando a síntese de iminas utilizando procedimentos clássicos descritos na literatura, que empregam agentes secantes, aquecimento e tubo Dean-Stark. Também foi realizada a síntese assistida por micro-ondas, que levou a uma drástica redução no tempo reacional (3 a 4 h) em comparação aos métodos tradicionais (20 a 48 h). Para o estudo modelo racêmico – acetofenona/1-metilfenilamina – a melhor taxa de conversão de formação da imina (E/Z)-1-fenil-N-(1-feniletil)etan-1-imina foi > 99 %. As condições reacionais utilizadas foram: irradiação por micro-ondas, 180 °C (sob potência e pressão variáveis), 4 h, catálise com ácido p-toluenossulfônico (APTS) e 2,5 equivalentes de amina. Reduzindo o excesso da amina para 1,1 equivalentes, a conversão diminuiu ligeiramente para 97 %, mantendo ainda uma excelente taxa de conversão. A razão E/Z das iminas nessas duas condições reacionais foram de 10:1 e 11:1, respectivamente. Para o estudo modelo quiral, obteve-se o ácido (E/Z)-2-((1-fenilletilideno)amino)propanóico, preparado a partir do aminoácido natural (L)-alanina com a acetofenona. As condições utilizadas foram as mesmas do modelo racêmico, porém, com 3 h de duração. Nessas condições, a conversão obtida foi de 53 % e razão E/Z de 11:1.
Adicionalmente, a amina quiral (R)-1-fenilpropan-2-amina, derivada do aminoácido (L)-fenilalanina foi obtida após 5 etapas reacionais, com rendimento global de 20 % e poderá ser utilizada para formação de iminas assimétricas, ampliando o leque de estruturas possíveis. Tais iminas serão o intermediário chave para síntese assimétrica de 1-indanonas por meio da ativação C(sp3)-H, sem o uso de ligantes ou bases quirais, propondo assim, uma abordagem alternativa e mais simples para esta metodologia.
This work presents the studies twards the synthesis of imines using classical procedures described in the literature, which employ drying agents, heating and Dean-Stark tube. Microwave-assisted synthesis was also performed, which led to a drastic reduction in reactional time (3 to 4 h) compared to the traditional methods (20 to 48 h). The highest conversion that forms (E/Z)-1-phenyl-N-(1-phenylethyl)ethan-1-imine achieved for the racemic model – acetophenone/1-methylphenylamine – was > 99 %. The conditions were microwave irradiation, 180 °C (variable power and pressure), 4 h, p-Toluenesulfonic acid (PTSA) and 2.5 amine eq. Reducing the excesso of the amine to 1.1 eq, the conversion slightly reduced to 97 %, still an excellent conversion rate. The E/Z ratio of imines in these two reactional conditions were 10:1 and 11:1, respectively. In the chiral model study, the (E/Z)-2-((1-phenylethylidene)amino)propanoic acid, derived from the natural amino acid (L)-alanine with acetophenone, was obtained in the same conditions for the racemic model (3 h instead). The conversion observed was 53 % and the E/Z ratio was 11:1. In addition, the chiral amine (R)-1-phenylpropan-2-amine, derived from the amino acid (L)-phenylalanine was obtained after 5 reaction steps, with overall yield of 20 %. It can be used for formation of asymmetric imines, expanding the range of possible structures. Such imines will be the key intermediate for asymmetric synthesis of 1-indanone through C(sp3)-H activation, without chiral ligands or chiral bases, thus proposing an alternative and simpler approach to this methodology.
This work presents the studies twards the synthesis of imines using classical procedures described in the literature, which employ drying agents, heating and Dean-Stark tube. Microwave-assisted synthesis was also performed, which led to a drastic reduction in reactional time (3 to 4 h) compared to the traditional methods (20 to 48 h). The highest conversion that forms (E/Z)-1-phenyl-N-(1-phenylethyl)ethan-1-imine achieved for the racemic model – acetophenone/1-methylphenylamine – was > 99 %. The conditions were microwave irradiation, 180 °C (variable power and pressure), 4 h, p-Toluenesulfonic acid (PTSA) and 2.5 amine eq. Reducing the excesso of the amine to 1.1 eq, the conversion slightly reduced to 97 %, still an excellent conversion rate. The E/Z ratio of imines in these two reactional conditions were 10:1 and 11:1, respectively. In the chiral model study, the (E/Z)-2-((1-phenylethylidene)amino)propanoic acid, derived from the natural amino acid (L)-alanine with acetophenone, was obtained in the same conditions for the racemic model (3 h instead). The conversion observed was 53 % and the E/Z ratio was 11:1. In addition, the chiral amine (R)-1-phenylpropan-2-amine, derived from the amino acid (L)-phenylalanine was obtained after 5 reaction steps, with overall yield of 20 %. It can be used for formation of asymmetric imines, expanding the range of possible structures. Such imines will be the key intermediate for asymmetric synthesis of 1-indanone through C(sp3)-H activation, without chiral ligands or chiral bases, thus proposing an alternative and simpler approach to this methodology.