RESUMEN
A novel integrated web-based system which can compute, visualise and store systematised key parameters of a reaction has been developed from open-source components. As a proof of concept, it has been used to rationalise and predict the regioselectivity of lithiation reactions as well as relative reactivity of substrates. Excellent agreement between the in silico analysis and experimental data was obtained.
RESUMEN
Multicomponent synthesis of 3-aminoimidazo[1,2-a]pyrimidines usually affords a product mixture containing varying amounts of the corresponding 2-amino regioisomer. Modified methods, particularly microwave heating, have been employed to suppress formation of this side-product, but none of the revised protocols are readily amenable to scale. A continuous flow adaptation was found to offer improved regioselectivity toward the targeted 3-amino regioisomer with significantly shorter reaction times and also widened the scope of the reaction to permit the use of aliphatic aldehyde building blocks.
Asunto(s)
Imidazoles/síntesis química , Pirimidinas/síntesis química , Aldehídos/química , Catálisis , Imidazoles/química , Estructura Molecular , Pirimidinas/química , EstereoisomerismoRESUMEN
Conducting low-temperature organometallic reactions under continuous flow conditions offers the potential to more accurately control exotherms and thus provide more reproducible and scalable processes. Herein, progress towards this goal with regards to the lithium-halogen exchange/borylation reaction is reported. In addition to improving the scope of substrates available on a research scale, methods to improve reaction profiles and expedite purification of the products are also described. On moving to a continuous system, thermocouple measurements have been used to track exotherms and provide a level of safety for continuous processing of organometallic reagents. The use of an in-line continuous liquid-liquid separation device to circumvent labour intensive downstream off-line processing is also reported.
