Organische Synthese: Vormarsch der Maschinen

Abstract

Die organische Synthese ist im Wandel begriffen: Da Forschungsetats zunehmend gekürzt werden und der Einfluss chemischer Verfahren auf die Umwelt genau geprüft wird, wird immer deutlicher, dass der effiziente Einsatz von Personal im Labor mindestens so bedeutsam ist wie die Materialverwendung. Neue Techniken und Maschinen verändern unsere Arbeitsweise, und indem die zuvor genannten Punkte — Personal und Material – erfasst werden, ermöglichen sie es Chemikern in Forschungslaboratorien, einen eher ganzheitlichen Ansatz für ihre Tätigkeit zu finden. Moderne Entwicklungen auf diesem Gebiet fördern multidisziplinäres Vorgehen mit dem Ergebnis effizienterer Arbeit. Dieser Aufsatz behandelt die Konzepte, Verfahren und Methoden, die weitreichende Implikationen für die Chemie insgesamt haben. Thematisch ist der Aufsatz nach unterschiedlichen Anwendungsmöglichkeiten gegliedert, und neuere Anwendungen in innovativen Forschungslabors werden beschrieben.

Sampling and Analysis in Flow: The Keys to Smarter, More Controllable, and Sustainable Fine‐Chemical Manufacturing

“…Real‐time release testing (RTRT) using information feedback loops has been implemented for quite some time in the petrochemical, food, and beverage industries. In the last two decades, pharmaceutical and fine‐chemical manufacturers have begun to actively seek similar technologies for producing small molecules in compliance with the guidelines of environmental and drug‐manufacturing regulatory agencies [27–30] . One key difference in the CM PAT of the pharmaceutical and fine‐chemical sectors and that of other industries lies in the complexity associated with the analysis of outputs from chemical or biochemical transformations.…”

“…Integrating at least one analyzer to aflow reactor is empowering,asthe unified PAT-enabled CM system alerts process chemists to transient process failures at the earliest possible moment and helps adjustments to be made to mitigate deviations.R eal-time release testing (RTRT) using information feedback loops has been implemented for quite some time in the petrochemical, food, and beverage industries.I nt he last two decades,p harmaceutical and fine-chemical manufacturers have begun to actively seek similar technologies for producing small molecules in compliance with the guidelines of environmental and drugmanufacturing regulatory agencies. [27][28][29][30] One key difference in the CM PATo ft he pharmaceutical and fine-chemical sectors and that of other industries lies in the complexity associated with the analysis of outputs from chemical or biochemical transformations.Q uite often, pharmaceutical or fine-chemical products bear structural features that make end products sensitive to the slightest change in the reaction conditions that produce them in the first place.S mall perturbations in the reaction matrix or the conditions during analysis can drastically impact the measurement of the composition of matter,t hereby providing misleading analytical information from the integrated PATa nd raising concerns over the validity of the integrated QC/QA protocol. AP AT tool should operate in such away that the composition of matter does not change during sampling.…”

“…Ar eport in 2016 demonstrated the use of in-line UV/Vis PATf or two example processes:1 )the esterification of salicylic acid and 2) the cross-coupling of 4-bromotoluene (30)and phenyl boronic acid (31)using aplug-and-play flow reactor design (Figure 21). [59] Thea uthors measured the conversion of the starting reagents into products by monitoring the rise in the product signal at aspecific wavelength over reactor residence time.T he accuracy of the quantitative UV/ Vism easurements was validated by comparing the in-line UV/Vis PATwith off-line LC analysis.…”

Continuous‐Flow Synthesis of Biaryls by Negishi Cross‐Coupling of Fluoro‐ and Trifluoromethyl‐Substituted (Hetero)arenes

“…[8] We anticipated that XPhos-based precatalyst 6,w hich has previously been shown to provide excellent results for C(sp 2 )ÀC(sp 2 )N egishi cross-coupling reactions under batch conditions,would prove suitable in the current system. [10,11] Owing to the improved heat transfer in continuous-flow reactors,t he temperature of exothermic organometallic reactions can be accurately controlled, thus providing scalable and reproducible processes.The utilization of organolithium species in continuous-flow synthesis was pioneered by Yoshida and co-workers. [10,11] Owing to the improved heat transfer in continuous-flow reactors,t he temperature of exothermic organometallic reactions can be accurately controlled, thus providing scalable and reproducible processes.The utilization of organolithium species in continuous-flow synthesis was pioneered by Yoshida and co-workers.…”

Continuous‐Flow Synthesis of Biaryls by Negishi Cross‐Coupling of Fluoro‐ and Trifluoromethyl‐Substituted (Hetero)arenes

“…[9] Flow conditions offer asafe alternative to batch reactions whenever dangerous or unstable intermediates or reagents are involved. [10,11] Owing to the improved heat transfer in continuous-flow reactors,t he temperature of exothermic organometallic reactions can be accurately controlled, thus providing scalable and reproducible processes.The utilization of organolithium species in continuous-flow synthesis was pioneered by Yoshida and co-workers. [12,13] Several examples demonstrated the successful transfer of organolithium reactions from batch to continuous-flow conditions,r esulting in improvements of yield and functional-group compatibility.…”