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

• well. Microreactors, as a preferred process intensification tool, have gained considerable importance due to their many advantages over conventional batch reactors, including rapid heat and mass transfer, high surface area-to-volume ratios for dispersed media, and short processing times [10]. Indeed

• , there is indication that biocatalysis under flow conditions provided by a microreactor can result in better process control by external numbering-up in which each subunit of reaction can be examined separately with enhanced productivity [11]. Microreactors have been used in many fields of chemistry such

• intensification and biocatalysis has been reviewed [24]. Asanomi et al. have also summarized the use of microfluidic devices in biocatalysis and compared them with conventional batch reactors [25]. The advantages of enzymatic microreactors have been demonstrated both in process development and for the production

One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor

• Mark C. Bagley,
• Vincenzo Fusillo,
• Robert L. Jenkins,
• M. Caterina Lubinu and
• Christopher Mason

Beilstein J. Org. Chem. 2013, 9, 1957–1968, doi:10.3762/bjoc.9.232

• corresponding alcohol 7 [44], the transfer from batch reactor operation to continuous flow processing was efficient and required little further optimization. Furthermore, we showed that methodology developed using different reaction platforms, including commercial microreactors and stainless steel continuous

Raman spectroscopy as a tool for monitoring mesoscale continuous-flow organic synthesis: Equipment interface and assessment in four medicinally-relevant reactions

• Trevor A. Hamlin and
• Nicholas E. Leadbeater

Beilstein J. Org. Chem. 2013, 9, 1843–1852, doi:10.3762/bjoc.9.215

• chemistry and optimizing reaction conditions, one option is to use inline product analysis. This opens the avenue for fast, reliable assay in comparison with the traditional approach in which performance is evaluated based on offline product analysis. When interfaced with microreactors, inline analysis has

Flow Giese reaction using cyanoborohydride as a radical mediator

• Takahide Fukuyama,
• Takuji Kawamoto,
• Mikako Kobayashi and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2013, 9, 1791–1796, doi:10.3762/bjoc.9.208

• efficient reaction in the microreactors. We then carried out the optimization of the reaction conditions for the secondary and tertiary alkyl iodides, 2-iodooctane (1b) and 1-iodoadamantane (1c), reacting with ethyl acrylate. We were pleased to find that under similar reaction conditions (70 °C, 10–15 min

Gallium-containing polymer brush film as efficient supported Lewis acid catalyst in a glass microreactor

• Rajesh Munirathinam,
• Roberto Ricciardi,
• Richard J. M. Egberink,
• Jurriaan Huskens,
• Michael Holtkamp,
• Herbert Wormeester,
• Uwe Karst and
• Willem Verboom

Beilstein J. Org. Chem. 2013, 9, 1698–1704, doi:10.3762/bjoc.9.194

• model substrate, and for the formation of oxazoles by ring closure of ortho-hydroxy oximes. The catalytic activity of the microreactor could be maintained by periodic reactivation by treatment with GaCl3. Keywords: dehydration of oximes; flow chemistry; gallium; microreactors; Lewis acid catalysis

• ; polymer brushes; Introduction Heterogeneous catalysis plays a crucial role in organic synthesis both in industry and academia. In the present situation, microreactors offer a number of benefits over classical setups [1][2][3]. Especially, heterogeneous catalysis in a continuous-flow microreactor is

• gaining growing attention, owing to its advantages such as increased surface-to-volume ratio, faster heat and mass transfer, only small amounts of reagents are handled, when compared to conventional laboratory equipment [4]. Heterogeneous catalysis in microreactors is carried out using two approaches, viz

Chemistry in flow systems III

• Andreas Kirschning

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

• Ehrfeld Mikrosystem BTS and by CPC (Cellular Process Chemistry Systems) are marvelous examples of these engineered driven achievements. In the late nineties, organic chemists from both industry and academia, which included our group, became involved in the use of microreactors and provided a myriad of

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

• 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

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• intermediates that can be converted into various types of chiral ferrocene derivatives through diastereoselective ortho-lithiation [21]. Some years ago, the concept of flash chemistry was proposed, involving fast chemical synthesis by using flow microreactors, which enabled the use of highly reactive

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

• peroxide product present at any one time, and this can be reduced immediately upon leaving the reactor. The smaller reactor volumes involved in flow chemistry also mean that irradiation is efficient and hence that the singlet oxygen generated can react within its short lifetime. Falling-film microreactors

• . However, not all dual channel microreactors need suffer such low productivity; the oxidation of β-citronellol (24) has been performed in the dual channel reactor designed by Kim et al. and gave a daily output of 45.5 mmol (1.9 mmol/h) by using methylene blue as the sensitiser and a 16 W LED light source

• temperature gave high enantioselectivity. The low productivity of the 100 µL microreactor led the reaction to be transferred to an FEP macroflow reactor for further scale-up, which led to hugely increased productivity. This does, however, demonstrate the utility of microreactors for initial screening of

Photochemistry with laser radiation in condensed phase using miniaturized photoreactors

• Elke Bremus-Köbberling,
• Arnold Gillner,
• Frank Avemaria,
• Céline Réthoré and
• Stefan Bräse

Beilstein J. Org. Chem. 2012, 8, 1213–1218, doi:10.3762/bjoc.8.135

• Toxicology and Genetics, Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen, Germany 10.3762/bjoc.8.135 Abstract Miniaturized microreactors enable photochemistry with laser irradiation in flow mode to convert azidobiphenyl into carbazole with high efficiency

• combinatorial flow chemistry in lab-on-a-chip applications. Photochemical processes are in this case particularly interesting because of their enhanced molecular activation [8]. Photochemistry in microreactors is an emerging research area [9], and especially photocatalytic reactions have been investigated in

• material, which could reduce the yield of the desired reaction product. The multilayer system is placed in a stainless-steel frame. With this type of reactor, it is possible to realize a series of reactions in parallel by arranging the reactor chambers in an (n × m) matrix. The microreactors applied for

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

• microreactors has been developed. Reaction monitoring was achieved by using an inline ReactIR flow cell, which allows fast and convenient optimization of reaction parameters. The reductions proceeded well, and the desired products were isolated in high yields and with excellent enantioselectivities. Keywords

• incorporating inline analytical devices the progress of reactions can be monitored and analyzed in real time, allowing fast reaction screening and optimization [43][44][45][46][47][48][49][50][51][52][53][54][55]. Continuous flow microreactors have been applied to a number of standard transformations in organic

• lower reactivities were obtained. This can be explained by the better heat transfer in the microreactors as compared to the glass flask typically used in our batch reactions. The scope and applicability of the method was then tested on various 2-substituted quinolines (Table 4). In general the

The application of a monolithic triphenylphosphine reagent for conducting Appel reactions in flow microreactors

• Kimberley A. Roper,
• Heiko Lange,
• Anastasios Polyzos,
• Malcolm B. Berry,
• Ian R. Baxendale and
• Steven V. Ley

Beilstein J. Org. Chem. 2011, 7, 1648–1655, doi:10.3762/bjoc.7.194

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• peroxidase. All reactions are carried out in an aqueous microfluidic system consisting of a cascade of three microreactors separately loaded with zinc powder and immobilized enzymes. The observed low conversion of 19% and space-time yield of 4 g L−1 day−1 imply the need for optimization, but demonstrate the

• -enzymatic synthesis of grossamide (52) in a cascade of packed-bed reactors. E: Peroxidase [39]. Chemo-enzymatic synthesis of 2-aminophenoxazin-3-one (56) in a cascade of continuously operating packed-bed microreactors. E1: Hydroxyaminobenzene mutase; E2: Soybean peroxidase [40]. Continuous conversion of 3

Continuous preparation of carbon-nanotube-supported platinum catalysts in a flow reactor directly heated by electric current

• Alicja Schlange,
• Antonio Rodolfo dos Santos,
• Ulrich Kunz and
• Thomas Turek

Beilstein J. Org. Chem. 2011, 7, 1412–1420, doi:10.3762/bjoc.7.165

• this operation mode is that the yearly production rates can be rather small, comparable to pharmaceutical or fine chemical synthesis. With the advent of microreactors or minireactors continuous preparation methods have entered the organic chemist’s laboratory. This makes the small-scale preparation of

Translation of microwave methodology to continuous flow for the efficient synthesis of diaryl ethers via a base-mediated S_NAr reaction

• Charlotte Wiles and
• Paul Watts

Beilstein J. Org. Chem. 2011, 7, 1360–1371, doi:10.3762/bjoc.7.160

• tool for rapid reaction screening, a microwave-absorbing solvent is often required in order to achieve efficient reactant heating. In comparison, microreactors can be readily heated and pressurised in order to “super-heat” the reaction mixture, meaning that microwave-transparent solvents can also be

• sensor that monitors the system pressure throughout the course of an investigation. The software enables the effect of reaction time, temperature and reactant stoichiometry to be investigated in an automated manner whilst the system is operated, unattended, within a fume cupboard. The glass microreactors

• quantities of isolated materials, the production volume of such units is inherently small. With efficient heat and mass transfer key to the success of microreactors, it is important that these features are retained when flow-reactor volume is increased. If this is not the case then the same issues arise as

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

• ]. Microreactors are expected to have a significant impact on chemical synthesis and production because of their many advantageous characteristics, such as highly efficient mixing, efficient heat transfer ability, precise control over the residence time, and high operational safety. We have studied and developed

• practical organic syntheses using flow microreactors, and we have reported thus far examples of Pd-catalyzed coupling reactions [11][12][13], radical reactions [14][15][16], and photoreactions [17][18][19][20][21]. Carbonylation reactions are a powerful tool for the introduction of carbon monoxide into

Triple-channel microreactor for biphasic gas–liquid reactions: Photosensitized oxygenations

• Ram Awatar Maurya,
• Chan Pil Park and
• Dong-Pyo Kim

Beilstein J. Org. Chem. 2011, 7, 1158–1163, doi:10.3762/bjoc.7.134

• oxygenations of α-terpinene, citronellol, and allyl alcohols. Keywords: gas–liquid reaction; microreactor; photosensitization; singlet oxygen; Introduction Microreactors have recently attracted much interest among the scientific community for performing laboratory operations on small scales [1][2][3][4][5][6

• context triple-channel microreactors could be quite useful as they comprise all the required elements for photosensitized oxygenations, namely continuous-flow processing, large gas–liquid interfacial area, short molecular diffusion distances, and very high surface illumination homogeneity. The middle

• acetonitrile. Table 1 represents the technical data for a typical batch reactor (50 mL round bottom flask), dual channel and triple channel microreactors. Since the illuminated area/volume and gas–liquid interfacial area/volume were highest in the case of triple-channel microreactor, much improved results were

A practical microreactor for electrochemistry in flow

• Kevin Watts,
• William Gattrell and
• Thomas Wirth

Beilstein J. Org. Chem. 2011, 7, 1108–1114, doi:10.3762/bjoc.7.127

• supporting electrolytes have to be used, which must be removed after the reaction. As a result, only a few electrochemical processes for the production of organic compounds have been commercialized [3]. In microreactors, the distances between electrodes can be very small such that the two diffusion layers of

• hypervalent iodine compounds using electrochemistry [13]. Electrochemical microreactors for investigations of laminar flow have also been reported recently [14][15]. Results and Discussion The target of this research is to develop a simple and practical microreactor in which to carry out electrochemical

Microphotochemistry: 4,4'-Dimethoxybenzophenone mediated photodecarboxylation reactions involving phthalimides

• Oksana Shvydkiv,
• Kieran Nolan and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2011, 7, 1055–1063, doi:10.3762/bjoc.7.121

• enable extensive penetration of light even at high chromophore concentrations. In addition, products are removed from the irradiated area thus preventing light-induced follow-up reactions or decompositions [17][18][19]. Recently, a number of photoreactions in microreactors have therefore been described

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

• explanations for these highly unusual rate accelerations are presented. In addition, general aspects of reactor degradation, corrosion and contamination effects of importance to continuous flow chemistry are discussed. Keywords: flow chemistry; heterogeneous catalysis; microreactors; palladium; process

• 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

• toxic but also highly explosive, a scale-up of this batch protocol is clearly not possible. A key advantage of using microreactors compared to conventional batch reactors is the ability to process potentially hazardous compounds or reagents safely [1][2][3][4][5][6][7][8][9][29][30][31][32]. In a

Flow through reactors for organic chemistry: directly electrically heated tubular mini reactors as an enabling technology for organic synthesis

• Ulrich Kunz and
• Thomas Turek

Beilstein J. Org. Chem. 2009, 5, No. 70, doi:10.3762/bjoc.5.70

• synthesis have gained much interest during the last years. Micro reaction technology is now well known and applied in many laboratories [1][2], with many examples of its application in organic synthesis [3][4][5][6]. One aspect still preventing widespread use is the high cost of most microreactors and the

Controlling hazardous chemicals in microreactors: Synthesis with iodine azide

• Johan C. Brandt and
• Thomas Wirth

Beilstein J. Org. Chem. 2009, 5, No. 30, doi:10.3762/bjoc.5.30

• reaction conditions in microreactors. Keywords: azide; flow chemistry; hazardous reagents; microreactor; rearrangement; Introduction Microstructured devices have already found their way into organic synthesis, because they offer various advantages over traditional large-scale chemistry performed in

• potentially hazardous compounds is another advantage of microreactors as only very small amounts of compounds/reagents are handled. Large inventories of dangerous reagents and intermediates are not necessary. Azides are among the most versatile reagents in modern organic chemistry however they are not often

• homolytically cleaved and introduce azide moieties efficiently into molecules with weak carbon–hydrogen bonds such as benzyl ethers [15][16] or aldehydes [17][18]. Recently some other research groups have investigated the use of azides in chemistries performed in microreactors [19][20][21][22]. Results and

Asymmetric reactions in continuous flow

• Xiao Yin Mak,
• Paola Laurino and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2009, 5, No. 19, doi:10.3762/bjoc.5.19

• Xiao Yin Mak Paola Laurino Peter H. Seeberger Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Research Campus Golm, D-14424 Potsdam, Germany 10.3762/bjoc.5.19 Abstract An overview of asymmetric synthesis in continuous flow and microreactors is presented in

• this review. Applications of homogeneous and heterogeneous asymmetric catalysis as well as biocatalysis in flow are discussed. Keywords: asymmetric catalysis; biocatalysis; continuous flow; microreactors; solid phase synthesis; Introduction While many technological advancements have been made over

• been reported, and these have been performed in microfluidic flow systems [10][11] consisting usually of micro-scale channels. The use of microreactors has been found to be especially useful for catalyst/ligand screening, as only low loading of reagents is required. The enantioselective silyl-cyanation

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

• 100 trials without showing any loss of catalytic activity. Keywords: alcohol oxidation; flow chemistry; heterogeneous catalysis; microreactors; TEMPO; Introduction Microreactors have gained attention because they can help run chemical transformations more efficiently, more selectively, and with a

• 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

• it enables facile removal and recycling. We recently reported the development of an effective solid support for use in packed-bed microreactors [39], AMBERZYME® Oxirane (AO, 1), a commercially available resin with pendant epoxide functionalities designed for enzyme immobilization. AO is readily