No abstract

In einem einfachen Mikroreaktor gelang die dreistufige Synthese von Ibuprofen unter Flussbedingungen. Durch die Entwicklung einer Synthese, bei der Überschüsse an Reaktanten und Nebenprodukten die folgenden Reaktionen nicht stören, wird die Isolierung und Reinigung von Zwischenstufen überflüssig.

Solids go with the flow: A monodisperse flow in a microreactor provides an efficient method for keeping solid products away from channel walls. The use of a carrier phase, such as mineral oil, hexane, or toluene, enables solids to be synthesized without clogging of the reactor channels. Further injection points can be added to the microreactor to perform multistep syntheses (see picture).

We present a new microencapsulated catalyst and report its use in a tandem multicatalyst reaction. Using an encapsulation technique, we developed an active, site-isolated amine catalyst that is capable of catalyzing the addition of nitromethane to an aldehyde. When a second Lewis acid catalyst is added, the nitroalkene intermediate is trapped and converted to the corresponding Michael adduct. We show that if the amine catalyst is not encapsulated, the two catalysts cannot function together. Moreover, if the two reactions are performed in sequence rather than in tandem, the first reaction results in an undesired dinitro product and the desired Michael adduct is not formed.

In this paper, we describe the development and application of a multistep one-pot reaction that is made possible by the site isolation of two otherwise incompatible catalysts. We prepared a microencapsulated amine catalyst by interfacial polymerization and used it in conjunction with a nickel-based catalyst for the transformation of an aldehyde to a Michael adduct via a nitroalkene intermediate. The amine-catalyzed conversion of an aldehyde to a nitroalkene was found to proceed through an imine rather than a nitroalcohol. Kinetic studies indicated that the reaction is first order in both the nickel catalyst and the shell of the encapsulated amine catalyst. Furthermore, we provide evidence against interaction between amine and nickel catalysts and present kinetic data that demonstrates that there is a rate enhancement of the Michael addition due to the urea groups on the surface of the microencapsulated catalyst. We applied our one-pot reaction to the development of a new synthetic route for pregabalin that proceeds with an overall yield of 74%.