Continuous Flow Organic Synthesis under High‐Temperature/Pressure Conditions

Razzaq, Tahseen; Kappe, C. Oliver

doi:10.1002/asia.201000010

Cited by 265 publications

(158 citation statements)

References 191 publications

(126 reference statements)

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“…The beneficial thermal characteristics afforded by flow systems enable precise temperature control within a reactor, a point discussed in a review on the use of microfluidic systems at high temperatures and pressures for process intensification 46. Furthermore, operating reactors at high temperatures is a key component of “novel process windows”,47 a concept that describes how uncommon reaction regimes can be incorporated with chemical processes to maximize output.…”

Section: Extreme Temperaturesmentioning

confidence: 99%

Machine‐Assisted Organic Synthesis

et al. 2015

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In this Review we describe how the advent of machines is impacting on organic synthesis programs, with particular emphasis on the practical issues associated with the design of chemical reactors. In the rapidly changing, multivariant environment of the research laboratory, equipment needs to be modular to accommodate high and low temperatures and pressures, enzymes, multiphase systems, slurries, gases, and organometallic compounds. Additional technologies have been developed to facilitate more specialized reaction techniques such as electrochemical and photochemical methods. All of these areas create both opportunities and challenges during adoption as enabling technologies.

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Section: Extreme Temperaturesmentioning

confidence: 99%

Machine‐Assisted Organic Synthesis

et al. 2015

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“…Unexpected was that the allyl bromide had similar strong effect. Under the high temperatures used in the thermal Claisen rearrangement, which are typically set in microflow even higher [13,14], the allyl bromide decomposes to give propene and HBr. The latter acid can lead to the same decomposition rate of the Claisen product as the acid does.…”

Section: Introductionmentioning

confidence: 99%

Photo-Claisen Rearrangement of Allyl Phenyl Ether in Microflow: Influence of Phenyl Core Substituents and Vision on Orthogonality

2016

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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 photoClaisen 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.

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“…The positive impact of continuous flow chemistry on chemical processes is well studied and has been covered by many review articles. 1 The main benefits which are frequently cited are the improved heat and mass transfer, [2][3][4] greater reaction control, 5 the ease of heating solvents above their boiling point, 6 higher safety when dealing with reactive and hazardous intermediates 7 and relative simplicity of their automation and telescoping of multistep reactions. 8,9 Together these lead to overall process intensification.…”

Section: Introductionmentioning

confidence: 99%