Scaling Up UV-Mediated Intramolecular Photodehydro-Diels–Alder Reactions Using a Homemade High-Performance Annular Continuous-Flow Reactor

Czarnecki, Maciej; Wessig, Pablo

doi:10.1021/acs.oprd.8b00353

Cited by 19 publications

(30 citation statements)

References 35 publications

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“…This provided a uniform distribution and little variation in the reaction yield over the eight microcapillaries [92,93]. A similar approach has been reported for the scale up of a LSC-PM for solar chemistry [94] and for a homogeneous UV-promoted [4+2] cycloaddition [95].…”

Section: Scale-up Strategies and Designsmentioning

confidence: 55%

Flow Photochemistry: Shine Some Light on Those Tubes!

Sambiagio

Noël

2020

Trends in Chemistry

295

223

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Continuous-flow chemistry has recently attracted significant interest from chemists in both academia and industry working in different disciplines and from different backgrounds. Flow methods are now being used in reaction discovery/methodology, in scale-up and production, and for rapid screening and optimization. Photochemical processes are currently an important research field in the scientific community and the recent exploitation of flow methods for these methodologies has made clear the advantages of flow chemistry and its importance in modern chemistry and technology worldwide. This review highlights the most important features of continuous-flow technology applied to photochemical processes and provides a general perspective on this rapidly evolving research field. Microflow Technology and Photochemistry: A Perfect MatchThe use of light to promote chemical reactions has been exploited since the 18th century, but only recently a resurgence has been observed in synthetic organic chemistry, in particular due to the development of visible-light photoredox catalysis [1-5]. All transformations involving light (e.g., Figure 1A-D) must consider, besides classical chemical parameters (i.e., reaction conditions), the photophysical aspects of the sensitizer (see Glossary)/photocatalyst (when used), and the reactor design. The latter, although often neglected by chemists, is a critical aspect for the outcome of the studied chemical transformation. This includes, for example, the size, shape, and material of the reaction vessel, the characteristics and positioning of the light source(s), and heat-transfer properties, particularly when high-intensity lamps are used [6,7]. The engineering and technological aspects of photochemical processes are often at the basis of the irreproducibility and non-scalability of such transformations.According to the Beer-Lambert law, light transmittance decreases exponentially with the distance from the light source ( Figure 1F). For a standard batch reactor (diameter at least in the centimeter range), light intensity decreases considerably from the flask walls to the middle of the reaction mixture, resulting in slow reactions and nonhomogeneous irradiation of the reaction mixture. Performing photochemical reactions in microchannels (ID < 1 mm) allows a higher and more homogeneous photon flux, resulting in shorter reaction times and consequently less side-product formation due to over-irradiation, often observed in batch [8,9]. Another advantage of microflow chemistry, correlated with the large surface:volume ratio, is improved heat and mass transfer, with the possibility to perform mass-transfer-limited multiphasic reactions efficiently [10]. Reactive chemicals and intermediates can be handled more safely in flow than in batch, as no accumulation of dangerous components occurs within the confined reactor volume due to the continuous nature of the process. Together, these result in often faster, safer, and higher-yielding reactions, with the possibility to perform reactions under condition...

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Section: Scale-up Strategies and Designsmentioning

confidence: 55%

Flow Photochemistry: Shine Some Light on Those Tubes!

Sambiagio

Noël

2020

Trends in Chemistry

295

223

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“…This kind of reaction in batch is characterized by applying high substrate dilutions resulting in long reaction times and consequently in over‐irradiation of the corresponding products. Interestingly, the flow protocol could achieve yields up to 77 % and productivities up to 4.26 g per hour (Scheme ) …”

Section: Miscellaneousmentioning

confidence: 99%

Flow Chemistry for Cycloaddition Reactions

2020

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Continuous flow reactors form part of a rapidly growing research area that has changed the way synthetic chemistry is performed not only in academia but also at the industrial level. This Review highlights the most recent advances in cycloaddition reactions performed in flow systems. Cycloadditions are atom-efficient transformations for the synthesis of carbo-and heterocycles, involved in the construction of challenging skeletons of complex molecules. The main advantages of translating these processes into flow include using intensified conditions, safer handling of hazardous reagents and gases, easy tuning of reaction conditions, and straightforward scaling up. These benefits are especially important in cycloadditions such as the copper(I)-catalyzed azide alkyne cycloaddition (CuAAC), Diels-Alder reaction, ozonolysis and [2 + 2] photocycloadditions. Some of these transformations are key reactions in the industrial synthesis of pharmaceuticals.

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“…The intramolecular photodehydro‐Diels‐Alder reaction was described for the flow synthesis of (1,7)naphthalenophanes. Once again, the use of high dilutions proved to be essential to achieve higher yields and lower photodegradation (yield up to 77 %) …”

Section: Heterocyclic Synthesismentioning

confidence: 99%

Flow Chemistry: Towards A More Sustainable Heterocyclic Synthesis

2019

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Flow Chemistry is a revolutionary field in Organic Chemistry. By changing the conventional methods and apparatus applied in the chemical synthesis, flow chemistry emerges as a game changer for organic synthesis laboratories, in both academia and industries. Considered as a sustainable practice, flow processes play an important role in the development of fine chemical products and in drug discovery development pro- [a] The main advantages of flow chemistry are that it allows the reaction to be carried out safely with high selectivity, high reproducibility and reduced energy consumption/carbon footprint. These features make this emerging technology for organic synthesis desirable for green and sustainable chemical synthesis, giving the chemist time for work planning and design, instead of using it in repetitive tasks, [5b,12] as expressed by the CHEM21 project by awarding a green flag for continuousflow reactions, in opposition to an amber flag for those performed under batch conditions. [13] Pedro Brandão received his MSc in Pharmaceutical Sciences from the Faculty of Pharmacy -University of Porto, in 2011. Pursuing his passion on studies in the field of Drug Discovery and Development, he is currently undergoing his PhD studies in Chemistry, in the field of Catalysis and Sustainability. His main focus of work is the discovery of new drug candidates through sustainable techniques. Marta Pineiro received her Ph.D. in Organic Chemistry in 2003 in the University of Coimbra, Portugal, and since 2002 has been enrolled at the University of Coimbra, being at present Auxiliary Professor. Her research interests are in the area of sustainable organic synthesis, microwave-assisted organic synthesis and synthesis and biological applications of tetrapyrrolic macrocycles. Teresa M. V. D. Pinho e Melo studied Chemistry at the University of Coimbra, where she graduated in 1985, got her M. 7191CPBA) as the oxidizing agent, avoiding the handling of this expensive and explosive reagent. [25] Recently, Morodo et al. explored the synthesis of two very important oxiranes (epichlorohydrin and glycidol) from biobased glycerol, under flow conditions. As depicted in Scheme 1, and using pimelic acid as the catalyst (10 mol-%), a sequential hydrochlorination/dichlorination process allows high conversion of glycerol (> 99 %) into 1,3-dichloro-2-propanol, followed by the quantitative conversion into a separable mixture of glycidol and epichlorohydrin (2:3). The separation of these two products is performed by an in-line membrane separation system, which allows the first product to be collected in the aqueous phase, while the second is collected in MTBE. This heterocycle can be further used as a synthetic precursor to relevant APIs bearing -amino alcohol moieties (e.g., propranolol, alprenolol and naftopidil). [26] Scheme 1. Sequential flow setup for the preparation of glycidol and epichlorohydrin, important APIs synthetic intermediates.Scheme 3. Synthesis and inline purification of a bicyclic aziridine (SGMR = silicon-glass microfluidic react...

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Scaling Up UV-Mediated Intramolecular Photodehydro-Diels–Alder Reactions Using a Homemade High-Performance Annular Continuous-Flow Reactor

Cited by 19 publications

References 35 publications

Flow Photochemistry: Shine Some Light on Those Tubes!

Flow Photochemistry: Shine Some Light on Those Tubes!

Flow Chemistry for Cycloaddition Reactions

Flow Chemistry: Towards A More Sustainable Heterocyclic Synthesis

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