A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• Michael Andresini Leonardo Degannaro Renzo Luisi Flow Chemistry and Microreactor Technology FLAME-Lab, Department of Pharmacy – Drug Sciences, University of Bari “A. Moro”, Via E. Orabona 4, Bari, 70125, Italy 10.3762/bjoc.17.20 Abstract The reported flow-batch approach enables the easy

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• applied to various C–H functionalization reactions [92][93]. In 2017, Noël, Van der Eycken and co-workers hence astutely combined the dual catalysis strategy with flow microreactor technology to achieve C2-acylation of indole derivatives with aldehydes (Figure 30) [94]. Both electron-rich and electron

Photocatalytic trifluoromethoxylation of arenes and heteroarenes in continuous-flow

• Alexander V. Nyuchev,
• Ting Wan,
• Borja Cendón,
• Carlo Sambiagio,
• Job J. C. Struijs,
• Michelle Ho,
• Moisés Gulías,
• Ying Wang and
• Timothy Noël

Beilstein J. Org. Chem. 2020, 16, 1305–1312, doi:10.3762/bjoc.16.111

• , Road, North Chicago, Illinois 60064, United States of America 10.3762/bjoc.16.111 Abstract The first example of photocatalytic trifluoromethoxylation of arenes and heteroarenes under continuous-flow conditions is described. Application of continuous-flow microreactor technology allowed to reduce the

Safe and highly efficient adaptation of potentially explosive azide chemistry involved in the synthesis of Tamiflu using continuous-flow technology

• Cloudius R. Sagandira and
• Paul Watts

Beilstein J. Org. Chem. 2019, 15, 2577–2589, doi:10.3762/bjoc.15.251

• large scale synthesis in batch systems on the basis of safety concerns poised by the use of the potentially explosive azide chemistry and other hazardous chemistry. Therefore, problems inherent in scale-up are effectively eliminated or reduced, making microreactor technology a viable tool in the

Biocatalytic synthesis of the Green Note trans-2-hexenal in a continuous-flow microreactor

• Morten M. C. H. van Schie,
• Tiago Pedroso de Almeida,
• Gabriele Laudadio,
• Florian Tieves,
• Elena Fernández-Fueyo,
• Timothy Noël,
• Isabel W. C. E. Arends and
• Frank Hollmann

Beilstein J. Org. Chem. 2018, 14, 697–703, doi:10.3762/bjoc.14.58

• described in the literature to alleviate the inactivation issue described above [9][10][11][12]. The continuous-flow microreactor technology has emerged as a safe and scalable way to approach oxidation reactions [13][14]. Due to its small dimensions, hazardous reactions can be easily controlled, owing to

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• Flavio Fanelli Giovanna Parisi Leonardo Degennaro Renzo Luisi Department of Pharmacy – Drug Sciences, University of Bari “A. Moro”, FLAME-Lab – Flow Chemistry and Microreactor Technology Laboratory, Via E. Orabona 4, 70125, Bari. Italy 10.3762/bjoc.13.51 Abstract Microreactor technology and flow

• chemistry could play in the near future for a sustainable development. Keywords: flash chemistry; flow chemistry; green chemistry; microreactor technology; sustainable synthesis; Introduction Green chemistry’s birth was driven by the necessity to consider and face the urgent question of sustainability

• chemistry we can read Paul Anastas and John Warne’s 12 principles, set up in 1998, which illustrate the characteristics of a greener chemical process or product [2]. Microreactor technology and flow chemistry could play a pivotal role in the context of sustainable development. In fact, flow chemistry is

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• the production scale for quality control, the coupling of flow and microreactor technology with a good analytical method is a prerequisite. Several analytical methods have been used and these include fluorescence, ultraviolet–visible (UV–vis), RAMAN, infrared (IR) and nuclear magnetic resonance (NMR

• of NMR spectroscopy is a disadvantage for an analytical method, the power of this technique in structural determination compensates for its limitations. The application of NMR spectroscopy to analytical chemistry in flow, preparative flow chemistry and microreactor technology requires the use of

• (oxymethylmethylene)glycols. They used a new microreactor probe head that combined online flow 1H NMR spectroscopy (400 MHz) using microreactor technology (Figure 9). The microreactor NMR probe head was operated in stopped-flow. Under these conditions, the NMR flow cell is quickly filled with the reacting mixture of

Electron-transfer-initiated benzoin- and Stetter-like reactions in packed-bed reactors for process intensification

• Anna Zaghi,
• Daniele Ragno,
• Graziano Di Carmine,
• Carmela De Risi,
• Olga Bortolini,
• Pier Paolo Giovannini,
• Giancarlo Fantin and
• Alessandro Massi

Beilstein J. Org. Chem. 2016, 12, 2719–2730, doi:10.3762/bjoc.12.268

• -reaction phase and improving NHCs’ stability towards air and moisture [10][11]. Quite surprisingly, however, implementation of continuos-flow techniques with micro- and meso-reactors is rare in this field [12][13][14][15][16][17]. Indeed, microreactor technology is today a powerful tool for the fine

The in situ generation and reactive quench of diazonium compounds in the synthesis of azo compounds in microreactors

• Faith M. Akwi and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 1987–2004, doi:10.3762/bjoc.12.186

• be changed or modified to achieve the above mentioned green benefits in addition to other advantages. For example, isolated diazonium salts are known to be hazardous due to their explosive and unstable nature. However, microreactor technology makes it possible to safely perform reactions with

• the conventional way of performing reactions, the amount of waste generated is dealt with at the end of the reaction. On the contrary, microreactor technology enables the reduction of waste generated by increasing the atom efficiency of reactions and in so doing, the quantity of starting materials is

• reduced in turn minimizing the amount of waste generated. This aspect of microreactor technology will definitely prove to be quite important in the synthesis of these compounds more so that their production, however important they are, has adverse effects on the environment, mammals [20][21] and aquatic

A flow reactor setup for photochemistry of biphasic gas/liquid reactions

• Josef Schachtner,
• Patrick Bayer and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2016, 12, 1798–1811, doi:10.3762/bjoc.12.170

• to enter the field of microreactor technology for organic reactions at a reasonable price and effort. This detailed report on the theoretical, technical, and chemical aspects of a non-expert application of a home-built microreactor to a standard chemical reaction is specifically intended to stimulate

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• hydroxamic acid (5, SAHA, Figure 1) [43]. Another early application of microreactor technology was reported in 2005 detailing the assembly and subsequent decoration of the fluoroquinolinone scaffold 6 resulting in the synthesis of a library of analogues including the well-known antibiotic ciprofloxacin (6

• step approach towards ibuprofen (16) using microreactor technology [48]. A fully continuous process was aspired to, in which only final purification was to be performed off-line at the end of the sequence. Each of the individual steps were first optimised in flow being mindful of the reagents used in

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• fragments, based on the synthetic improvements and also the benefits of the continuous-flow microreactor technology herein described, is currently ongoing in our laboratory and it will be reported in due course. Besides the length of the carbohydrate haptens, the saccharide loading onto the protein is

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• microreactor technology to overcome long-standing problems in synthetic organofluorine chemistry are showcased. Reactions using hazardous fluorinating reagents Direct fluorination employing elemental fluorine (F2) is one of the most straightforward methods to make fluorine-containing molecules with high atom

• and extremely fast, frequently explosive. So it is difficult to control direct fluorination reactions with F2 gas in conventional batch reactors. In 1999, the pioneering work using flow microreactor technology for direct fluorination was reported by Chambers and Spink (Scheme 1) [26]. Utilizing the

• production of PET agents with automation and ease of in-line purification is suitable for hospital use. To date, continuous flow microreactor technology has shown potential for synthesis of [18F]-radiolabeled molecular imaging probes such as [18F]FDG, [18F]fallypride, [18F]annexin, and so on, which were made

A combined continuous microflow photochemistry and asymmetric organocatalysis approach for the enantioselective synthesis of tetrahydroquinolines

• Erli Sugiono and
• Magnus Rueping

Beilstein J. Org. Chem. 2013, 9, 2457–2462, doi:10.3762/bjoc.9.284

• ][11][12][13][14][15][16][17]. In the past years, continuous-flow chemistry has received considerable attention and microstructured continuous-flow devices have emerged as useful devices for different chemical reactions [18][19][20][21][22]. Microreactor technology offers numerous practical advantages

Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support

• Jagdish D. Tibhe,
• Hui Fu,
• Timothy Noël,
• Qi Wang,
• Jan Meuldijk and
• Volker Hessel

Beilstein J. Org. Chem. 2013, 9, 2168–2179, doi:10.3762/bjoc.9.254

• enzymatic microreactors (with other enzymes, having no availability limitation) and this result in much higher productivities. In this paper, we made a first step towards a critical view on the commercial potential for high-priced pharmaceutical products using enzymatic microreactor technology. Experimental

Ethyl diazoacetate synthesis in flow

• Mariëlle M. E. Delville,
• Jan C. M. van Hest and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2013, 9, 1813–1818, doi:10.3762/bjoc.9.211

• conditions, a production yield of 20 g EDA day−1 was achieved using a microreactor with an internal volume of 100 μL. Straightforward scale-up or scale-out of microreactor technology renders this method viable for industrial application. Keywords: diazo compounds; diazotization; ethyl diazoacetate (EDA

• ); flow chemistry; microreactor technology; Introduction Diazo compounds are frequently used versatile building blocks in organic chemistry [1][2]. From this class of compounds diazomethane and ethyl diazoacetate (1, EDA) are arguably the synthetically most useful ones. Due to the potentially explosive

• chemical synthesis is performed. In particular continuous-flow microreactor technology offers multiple advantages over batch chemistry, including the inherently safe conducting of reactions due to the small reactor dimensions, efficient heat transport and excellent control over the reaction conditions [6

Chemistry in flow systems III

• Andreas Kirschning

Beilstein J. Org. Chem. 2013, 9, 1696–1697, doi:10.3762/bjoc.9.193

• synthetic examples. The combined work of experts from engineering and chemical synthesis was highly fruitful and is so until today. This combination of expertise has catalyzed the development of microreactor technology in the applied context of synthesis and production. Chemical engineers depend on input

Hypervalent iodine/TEMPO-mediated oxidation in flow systems: a fast and efficient protocol for alcohol oxidation

• Nida Ambreen,
• Ravi Kumar and
• Thomas Wirth

Beilstein J. Org. Chem. 2013, 9, 1437–1442, doi:10.3762/bjoc.9.162

• successfully achieved by using microreactor technology. This method can be used as an alternative for the oxidation of various alcohols achieving excellent yields and selectivities in significantly shortened reaction times. Keywords: alcohols; carbonyl compounds; flow chemistry; microreactor; oxidation

• platforms to perform reactions under continuous flow rather than in batch mode has led to improvements regarding safety and sustainability. Microreactor technology can be beneficial over classical approaches in a variety of chemical reactions. Many reactions can benefit from the properties of microreactors

Continuous-flow catalytic asymmetric hydrogenations: Reaction optimization using FTIR inline analysis

• Magnus Rueping,
• Teerawut Bootwicha and
• Erli Sugiono

Beilstein J. Org. Chem. 2012, 8, 300–307, doi:10.3762/bjoc.8.32

• : asymmetric reduction; binolphosphoric acid; Brønsted acid; Hantzsch dihydropyridine; IR spectroscopy; real-time analysis; Introduction In recent years, a growing interest in microreactor technology has been seen in the scientific community and the development of microfabricated reaction systems is actively

• pursued. Microreactor technology offers numerous advantages, including precise control of reaction variables, enhanced mixing quality, improved operational safety, reduced reagent consumption and ready scale-up of chemical processes. Due to the high surface-area-to-volume ratios of microstructured

Koch–Haaf reaction of adamantanols in an acid-tolerant hastelloy-made microreactor

• Takahide Fukuyama,
• Yu Mukai and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2011, 7, 1288–1293, doi:10.3762/bjoc.7.149

• : continuous flow system; hastelloy; Koch–Haaf reaction; microreactor; Introduction The recent evolution of microreactor technology has allowed synthetic chemists to use this precisely sophisticated reaction apparatus in place of the well-established glassware batch flask [1][2][3][4][5][6][7][8][9][10

Unusual behavior in the reactivity of 5-substituted-1H-tetrazoles in a resistively heated microreactor

• Bernhard Gutmann,
• Toma N. Glasnov,
• Tahseen Razzaq,
• Walter Goessler,
• Dominique M. Roberge and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2011, 7, 503–517, doi:10.3762/bjoc.7.59

• intensification; Introduction Microreactor technology has opened up new avenues for synthetic organic chemistry [1][2][3][4][5][6] and the chemical manufacturing industry [7][8]. Traditionally, most synthetic transformations performed in microreactors have involved ambient or even low-temperature conditions in

A biphasic oxidation of alcohols to aldehydes and ketones using a simplified packed- bed microreactor

• Andrew Bogdan and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2009, 5, No. 17, doi:10.3762/bjoc.5.17

• higher degree of safety [1][2][3][4][5][6][7][8][9][10][11][12]. Alcohol oxidations are well suited for microreactors due to high by-product formation, catalyst contamination and safety concerns often associated with scale-up in batch reactors [13]. Recent developments in microreactor technology and