Continuous-Flow Preparation of γ-Butyrolactone Scaffolds from Renewable Fumaric and Itaconic Acids under Photosensitized Conditions

Gérardy, Romaric; Winter, Marc; Horn, Clemens R.; Vizza, Alessandra; Hecke, Kristof Van; Monbaliu, Jean‐Christophe M.

doi:10.1021/acs.oprd.7b00314

Cited by 28 publications

(20 citation statements)

References 34 publications

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“…A nice example has been reported by Beeler for the large-scale synthesis of analogs of the natural products aglain and rocaglate, obtained with 1.16-g h À1 throughput ( Figure 5A) [87]. This technique is particularly useful in the case of commercial reactors with well-defined reactor lengths, which can be combined in series with minimum alteration to the system [88,89].…”

Section: Scale-up Strategies and Designsmentioning

confidence: 86%

Flow Photochemistry: Shine Some Light on Those Tubes!

Sambiagio

Noël

2020

Trends in Chemistry

313

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: 86%

Flow Photochemistry: Shine Some Light on Those Tubes!

Sambiagio

Noël

2020

Trends in Chemistry

313

223

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“…Our group studied the upgrading of fumaric ( 188 ) and itaconic ( 192 ) acids into γ‐butyrolactones ( 238 – 242 ), in lab‐ and pilot‐scale continuous flow glass photoreactors (Figure ) . In‐line NMR monitoring was also implemented, and ensured rapid optimization of the process.…”

Section: Continuous Flow Upgrading Of Biosourced Platform Moleculesmentioning

confidence: 99%

Continuous Flow Organic Chemistry: Successes and Pitfalls at the Interface with Current Societal Challenges

et al. 2018

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This review intends to provide the reader with a clear and concise overview of how preparative continuous flow organic chemistry could potentially impact on current important societal challenges. These societal challenges include health/well‐being and sustainable development. Continuous flow chemistry has enabled significant advances for the manufacturing of pharmaceuticals, as well as for biomass valorization toward a biosourced chemical industry. Examples related to pharmaceutical production are herein focused on (a) the implementation of flow chemistry to reduce the occurrence of drug shortages, (b) continuous flow manufacturing of orphan drugs, (c) continuous flow preparation of active pharmaceuticals listed on the WHO list of essential medicines and (d) perspectives for the manufacturing of peptide‐based pharmaceuticals. Examples related to sustainable development are focused on the valorization of biosourced platform molecules. Besides positive impacts on societal challenges, this review also illustrates some of the potentially most threatening perspectives of continuous flow technology within the actual context of terrorism and drug abuse.

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“…Monbaliu and co-workers have reported a photochemical radical addition of isopropanol-derived to maleic or fumaric acid to obtain γ-butyrolactone scaffolds under scalable continuous-flow conditions. 84 γ-Butyrolactones are reported to be building blocks for the preparation of biologically relevant molecules and are present in many natural products, such as paraconic acids and trisubstituted γ-butyrolactones, which show antibiotic and antitumor properties. 85 With a simple methodology, this kind of heterocyclic compound could be synthesized using a lab-scale mesofluidic reactor with inline NMR spectroscopy, enabling fast optimization of the reaction parameters.…”

Section: Organic Process Research and Developmentmentioning

confidence: 99%

Light on the Horizon: Current Research and Future Perspectives in Flow Photochemistry

Politano

Oksdath‐Mansilla

2018

Org. Process Res. Dev.

152

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The research area of synthetic organic photochemistry is a powerful tool for creating both natural products and molecules with high structural complexity, in a simple way and under mild conditions. However, because of the challenges in scaling-up, it has been difficult to apply a photochemical reaction in an industrial process. Flow chemistry provides an opportunity for better control over the conditions of the reaction and, additionally, improved reaction selectivity and enhanced reproducibility. Taking into account that significant interest has focused on the use of flow photochemistry as a method for the synthesis of heterocycles and its applications in target-oriented synthesis over the last few years, the aim of this review is to highlight the recent efforts to apply flow photochemistry methodology to diverse reactions as a greener and more scalable process for the pharmaceutical and fine chemical industries. Additionally, the review highlights future perspectives in the development of scale-up strategies, combining photochemical reactions in the continuous flow multistep synthesis of organic molecules, being of interest for scientists and engineers alike.

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Continuous-Flow Preparation of γ-Butyrolactone Scaffolds from Renewable Fumaric and Itaconic Acids under Photosensitized Conditions

Cited by 28 publications

References 34 publications

Flow Photochemistry: Shine Some Light on Those Tubes!

Flow Photochemistry: Shine Some Light on Those Tubes!

Continuous Flow Organic Chemistry: Successes and Pitfalls at the Interface with Current Societal Challenges

Light on the Horizon: Current Research and Future Perspectives in Flow Photochemistry

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