Claisen-Umlagerung im Ruehr- und Durchflussbetrieb : Verstaendnis des Mechanismus und Steuerung der Einflussgroessen : the Claisen rearrangement in flow and batch processing : mechanism exploration and control over influencing factors.

Die Claisen-Umlagerung wurde in über 100 Jahren durch zahlreiche Forscher äußerst eingehend im Rührbetrieb untersucht. Insbesondere der Reaktionsmechanismus wurde in allen Details erforscht. Quantenmechanische Modellierung und moderne Kurzzeit-Spektroskopie haben hier ganz neue Impulse gegeben. Auch wurden schon erste Erfahrungen im Durchflussbetrieb in Mikroreaktoren gesammelt. Wie für viele andere Reaktionen so konnte eine massive Beschleunigung in neuen Prozessfenstern erreicht werden. Dieser Übersichtsartikel zeigt, dass das wahre Potenzial dennoch darauf wartet, für den Mikroreaktorbetrieb entdeckt zu werden. The Claisen rearrangement has been extensively studied over the past 100 years in batch mode. Especially the reaction mechanism has been determined in all details. Quantum-mechanical modelling and ultrashort pulse spectroscopy have recently provided entirely new insight. First experiments were carried out in microreactors using flow chemistry. An enhancement of the yield and selctivity in the new processing windows has been observed. This review shows, that the true and full potential has still not been fully explored for the microreactor processing

The Claisen rearrangement - part 2 : impact factor analysis of the Claisen rearrangement, in batch and in flow

In Part 2, the factors impacting the Claisen rearrangement both in batch and flow processing are analyzed, including the choice of substituent, catalyst, temperature, pressure, concentration, flow rates, and solvent. Part 1 of this review series discussed the potential of using short-time spectroscopy and quantum mechanical calculations to elucidate the mechanism and transition state of the Claisen rearrangement. Flow processing offers profound opportunities for studying these factors known to impact the Claisen rearrangement done in batch. It is shown that the same impact factors also rule flow processing, yet now superposed by the very different residence and reaction time settings and by novel process windows which go beyond conventional processing. As a result, massive intensification can be reached and a mechanistic analysis can be done in entirely unpaved processing fields. This links to the analysis given in part 1: it is likely that flow processing can further promote the understanding of the mechanism and transition state of the Claisen rearrangement and, thereby, promote the achievement of better reaction performance

Photo-claisen rearrangement of allyl phenyl ether in micro-flow: influence of phenyl core substituents and vision on orthogonality

We converted diverse commercial meta-substituted phenols to the allyl-substituted precursors via nucleophilic substitution using batch technology to allow processing these in microflow by means of the photo-Claisen rearrangement. The latter process is researched on its own, as detailed below, and also prepares the ground for a fully continuous two-step microflow synthesis, as outlined above. It is known that batch processing of electronically deactivated phenols (e.g., bearing a cyano or nitro group) has several orders of magnitude lower reactivity than their parental counterparts [1]. Thus, we here explore if the high quantum yield of microflow, yet at very short residence time, is sufficient to activate the deactivated molecules. In addition, the realization of a true orthogonal two-step flow synthesis can open the door to a large synthetic scope of our approach and possibly overcome limitations due to missing orthogonality of our previously reported thermal approach of combined nucleophilic substitution-Claisen rearrangement in microflow. Consequently, we make for our photo microflow approach an orthogonality check, as previously reported for the thermal approach, and compare both. To get a broader picture, we have investigated some major parametric sensitivities such as the irradiation intensity, the choice of solvent, the reactant concentration, and, most notably, the influence of the substitution pattern. The irradiation intensity was varied by increasing distance between a lamp and the microflow capillary. In addition, the normal photo-Claisen microflow process (at room temperature) is compared to a high-temperature photo-Claisen microflow process, to check the potential of such novel process window [2]. This is difficult to realize in batch, as the combination of strong ultraviolet (UV) irradiation and high temperature causes a high hazard potential. Yet, under microflow, this can be safely handled