Catalizadores bimetálicos en base a cobalto y níquel para aminación reductiva de nitroarenos empleados en la síntesis de benzimidazoles de interés farmacéutico.
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Date
2024
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Universidad de Concepción
Abstract
Los benzimidazoles son bloques de construcción relevantes para la preparación de una amplia gama de fármacos. En los últimos años, los catalizadores metálicos heterogéneos han surgido como una alternativa sustentable en la preparación de benzimidazoles a partir de aminación reductiva de 2-nitroanilina y aldehídos. De los metales comúnmente utilizados, Ni y Co han mostrado características promisorias para ser empleados como fases activas en este tipo de reacción. No obstante, aleaciones bi-metálicas Ni-Co podrían producir catalizadores superiores en eficiencia y reciclabilidad para la producción de benzimidazoles.
Es por lo anterior, que se propuso en esta tesis doctoral obtener catalizadores mono- y bi-metálicos mediante reducción asistida por H2 de óxidos mixtos del tipo NixCo1-xTiO3 que generen catalizadores del tipo NixCo1-x/TiO2 (x : 0, 0.1, 0.3, 0.5, 0.7, 0.9, 1) para utilizarlos en la aminación reductiva de 2 nitroanilina con diversos benzaldehídos para producir 2-fenilbenzimidazoles.
El diseño de los catalizadores involucró un proceso de reducción térmica que indujo el colapso de la estructura cristalina del oxido mixto produciendo la formación de nanopartículas mono- o bi-metálicas soportadas sobre TiO2, lo cual fue confirmado mediante diversas técnicas de caracterización fisicoquímica. Además, con el fin de incrementar la eficiencia de los catalizadores, la formulación más activa y selectiva fue soportada en materiales mesoestructurados del tipo SBA-15, KIT-6 y MCM-41. Los resultados catalíticos para la síntesis one-pot de 2-fenilbenzimidazol evidencian una correlación de actividad-selectividad en función del contenido de Ni-Co, donde el sistema Ni0.1Co0.9/TiO2 mostró la máxima eficiencia alcanzando una selectividad del 85% al producto de interés y elevada versatilidad a la producción de otros 2-fenilbenzimidazoles. La reciclabilidad de Ni0.1Co0.9/TiO2 alcanzó 10 ciclos de operación y mostró una discreta desactivación atribuida a procesos de oxidación y lixiviación de la aleación. En los sistemas soportados en SBA-15 y KIT-6 se observó una eficiencia catalítica superior comparada con Ni0.1Co0.9/TiO2 gracias al efecto confinamiento que confiere la estructura mesoporosa del soporte.
Finalmente, la reciclabilidad de los sistemas soportados disminuye drásticamente posterior al tercer ciclo de operación, lo cual se atribuyó a la escaza estabilidad que muestran los soportes mesoestructurados en base a SiO2 en el ambiente de la reacción.
Benzimidazoles are relevant building blocks for the preparation of a wide range of drugs. In recent years, heterogeneous metal catalysts have emerged as a sustainable alternative in the preparation of benzimidazoles from reductive amination of 2-nitroaniline and aldehydes. Among the commonly used metals, Ni and Co have shown promising characteristics to be used as active phases in this type of reaction. However, bi-metallic Ni-Co alloys could produce catalysts superior in efficiency and recyclability for the production of benzimidazoles. Therefore, it was proposed in this doctoral thesis to obtain mono- and bimetallic catalysts through H2-assisted reduction of mixed oxides of the NixCo1-xTiO3 type that generate catalysts of the NixCo1-x/TiO2 type (x: 0, 0.1, 0.3, 0.5, 0.7, 0.9, 1) to be used in the reductive amination of 2-nitroaniline with various benzaldehydes to produce 2-phenylbenzimidazoles. The design of the catalysts involved a thermal reduction process that induced the collapse of the crystalline structure of the mixed oxide, producing the formation of mono- or bi-metallic nanoparticles supported on TiO2, which was confirmed by several physicochemical characterization techniques. Furthermore, in order to increase the efficiency of the catalysts, the most active and selective formulation was supported on mesostructured materials like SBA-15, KIT-6 and MCM-41. The catalytic results for the one-step synthesis of 2 phenylbenzimidazole show a correlation of activity-selectivity by the Ni-Co content, where the Ni0.1Co0.9/TiO2 system showed the maximum efficiency, reaching a selectivity of 85% for the product of interest and high versatility for the production of other 2-phenylbenzimidazoles. The recyclability of Ni0.1Co0.9/TiO2 reached 10 operation cycles and showed a discrete deactivation attributed to oxidation and leaching processes of the alloy. In the systems supported on SBA-15 and KIT-6, a higher catalytic efficiency was observed compared to Ni0.1Co0.9/TiO2 attributed to the confinement effect conferred by the mesoporous structure of the support. Finally, the recyclability of the supported systems decreases drastically after the third cycle of operation, which was attributed to the poor stability shown by the mesostructured supports based on SiO2 in the reaction.
Benzimidazoles are relevant building blocks for the preparation of a wide range of drugs. In recent years, heterogeneous metal catalysts have emerged as a sustainable alternative in the preparation of benzimidazoles from reductive amination of 2-nitroaniline and aldehydes. Among the commonly used metals, Ni and Co have shown promising characteristics to be used as active phases in this type of reaction. However, bi-metallic Ni-Co alloys could produce catalysts superior in efficiency and recyclability for the production of benzimidazoles. Therefore, it was proposed in this doctoral thesis to obtain mono- and bimetallic catalysts through H2-assisted reduction of mixed oxides of the NixCo1-xTiO3 type that generate catalysts of the NixCo1-x/TiO2 type (x: 0, 0.1, 0.3, 0.5, 0.7, 0.9, 1) to be used in the reductive amination of 2-nitroaniline with various benzaldehydes to produce 2-phenylbenzimidazoles. The design of the catalysts involved a thermal reduction process that induced the collapse of the crystalline structure of the mixed oxide, producing the formation of mono- or bi-metallic nanoparticles supported on TiO2, which was confirmed by several physicochemical characterization techniques. Furthermore, in order to increase the efficiency of the catalysts, the most active and selective formulation was supported on mesostructured materials like SBA-15, KIT-6 and MCM-41. The catalytic results for the one-step synthesis of 2 phenylbenzimidazole show a correlation of activity-selectivity by the Ni-Co content, where the Ni0.1Co0.9/TiO2 system showed the maximum efficiency, reaching a selectivity of 85% for the product of interest and high versatility for the production of other 2-phenylbenzimidazoles. The recyclability of Ni0.1Co0.9/TiO2 reached 10 operation cycles and showed a discrete deactivation attributed to oxidation and leaching processes of the alloy. In the systems supported on SBA-15 and KIT-6, a higher catalytic efficiency was observed compared to Ni0.1Co0.9/TiO2 attributed to the confinement effect conferred by the mesoporous structure of the support. Finally, the recyclability of the supported systems decreases drastically after the third cycle of operation, which was attributed to the poor stability shown by the mesostructured supports based on SiO2 in the reaction.
Description
Tesis presentada para optar al grado académico de Doctora en Ciencias con mención en Química
Keywords
Catalizadores, Cobalto Análisis, Níquel, Benzimidazoles Síntesis