Maschinengestützte organische Synthese

Abstract

In diesem Aufsatz beschreiben wir, welche Konsequenzen der zunehmende Einsatz von Maschinen für organische Syntheseprogramme haben wird, wobei wir einen besonderen Schwerpunkt auf praktische Fragen des Reaktor‐Designs legen. In dem sich rasch verändernden und vielschichtigen Umfeld eines Forschungslabors ist eine modulare Ausstattung erforderlich, um hohe und tiefe Temperaturen und Drücke, Enzyme, Mehrphasensysteme, Schlämme, Gase und Organometallverbindungen in Einklang zu bringen. Um spezialisierte Reaktionsverfahren wie elektrochemische und photochemische Umsetzungen zu vereinfachen, wurden weitere Techniken entwickelt. All diese Teilgebiete halten Chancen und Herausforderungen bereit.

Silica‐Supported Silver Nitrate as a Highly Active Dearomatizing Spirocyclization Catalyst: Synergistic Alkyne Activation by Silver Nanoparticles and Silica

“…[20] Thus aw ide range of substituted aromatics are compatible with this simple,m ild method, and furthermore,e ven broader functional group tolerance was demonstrated by an extensive robustness screen, detailed in the Supporting Information. [21] Finally,t he use of our AgNO 3 -SiO 2 catalyst in ac ontinuous flow reaction [22] has been demonstrated. A0.1m solution of ynone 1a in toluene was simply passed through a1cm diameter column packed with 1.93 go fo ur standard 1w t% catalyst (19.3 mg of AgNO 3 )a taflow rate of 0.3 mL min À1 , concentrated in vacuo,and analyzed using 1 HNMR spectroscopy.T his reaction proceeded very efficiently,c onverting atotal of 23.6 gofynone 1a into spirocycle 2a in quantitative yield over a5 1h period (Scheme 3).…”

“…[14a] Pyrrole derivatives 5a-g are also well tolerated, with AgNO 3 -SiO 2 superior to unsupported AgNO 3 in all exam-ples.T he quantitative formation of spirocycles 6e-g is especially noteworthy,g iven the rarity of dearomatized products derived from 3-pyrroles. [21] Finally,t he use of our AgNO 3 -SiO 2 catalyst in ac ontinuous flow reaction [22] has been demonstrated. [21] Finally,t he use of our AgNO 3 -SiO 2 catalyst in ac ontinuous flow reaction [22] has been demonstrated.…”

Scale-up and Optimization of a Continuous Flow Synthesis of an α-Thio-β-chloroacrylamide

“…Over the past two decades, continuous processing has been employed with increasing frequency within the pharmaceutical and fine chemical industries for synthesis of active pharmaceutical ingredients (APIs) and natural products. − The process advantages inherent to flow chemistry include improved mass transfer and efficient heat transfer, facilitated by use of high surface-area-to-volume ratios of tubular reactors, safer access to extreme temperature and pressure conditions, enhanced reproducibility, inline workups, and automated operation. − Use of flow chemistry has been shown to enable additional possibilities for introducing process control via feedback loops, where suitable inline or online spectroscopic analysis allows the product profile of the reactor output to be managed in real time . Ease of scale-up is a further positive attribute of continuous processing; while traditional scale-up, with its associated challenges, is required for batch processes, additional, alternative options to achieve increased production are available through flow chemistry, whereby the process can either be run for longer (scale-out) or whereby multireactors can be run in parallel (numbering up). ,, …”

Supported Ionic Liquid‐Like Phases (SILLPs) as Immobilised Catalysts for the Multistep and Multicatalytic Continuous Flow Synthesis of Chiral Cyanohydrins

“…As for bulk ILs, structural changes/modifications in both cation and anion result in widely varying properties of the supported ILs, allowing their tuning for the specific needs of a given catalytic process ,. This approach combines the advantages of ILs as catalyst supports and modifiers with the use of solid phase chemistry, enabling not only flow processes, but the development of one‐pot multicatalytic multi‐component transformations integrating several synthetic reactions in a single process ,. The inspiration for this strategy is the biosynthetic machinery operating in nature, where potentially incompatible chemical transformations are separated by compartmentalisation, with reactive intermediates being passed from one unit to the next one.…”