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

• shortened reaction times. Several other oxidative processes have already been reported in flow chemistry [16]. Results and Discussion Benzyl alcohol was chosen as a substrate in order to examine the efficiency of the reaction and the microreactor flow system. In a batch reaction, the mixture of benzyl

Simple and rapid hydrogenation of p-nitrophenol with aqueous formic acid in catalytic flow reactors

• Rahat Javaid,
• Shin-ichiro Kawasaki,
• Akira Suzuki and
• Toshishige M. Suzuki

Beilstein J. Org. Chem. 2013, 9, 1156–1163, doi:10.3762/bjoc.9.129

• was reduced via hydrogen transfer from formic acid to p-nitrophenol and not by hydrogen generated by dehydrogenation of formic acid. Keywords: catalytic tubular reactor; flow chemistry; formic acid; hydrogenation; p-aminophenol; p-nitrophenol; Introduction The flow reaction process enables

Camera-enabled techniques for organic synthesis

• Steven V. Ley,
• Richard J. Ingham,
• Matthew O’Brien and
• Duncan L. Browne

Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118

• of the future. Keywords: automation; computer vision; digital camera; flow chemistry; machine-assisted synthesis; Introduction The increasing prevalence of digital camera technology for capturing images, videos and visible information is having a profound impact on many aspects of our modern

• , traditional research facilities are extremely expensive to commission and run, and yet for a significant proportion of their lives they are under-used or even lying vacant. To overcome some of these inefficient practices, continuous processing methods such as flow chemistry [26][27][28][29][30][31][32] and

3D-printed devices for continuous-flow organic chemistry

• Vincenza Dragone,
• Victor Sans,
• Mali H. Rosnes,
• Philip J. Kitson and
• Leroy Cronin

Beilstein J. Org. Chem. 2013, 9, 951–959, doi:10.3762/bjoc.9.109

• processing advantages of flow chemistry for the synthesis of organic compounds. Robust and inexpensive 3D-printed reactionware devices are easily connected using standard fittings resulting in complex, custom-made flow systems, including multiple reactors in a series with in-line, real-time analysis using an

• ATR-IR flow cell. As a proof of concept, we utilized two types of organic reactions, imine syntheses and imine reductions, to show how different reactor configurations and substrates give different products. Keywords: 3D printing; flow chemistry; flow IR; in-line analysis; imine reduction; imine

• synthesis; millifluidics; reactionware; Introduction The use of flow chemistry and 3D-printing technology is expanding in the field of organic synthesis [1][2][3][4][5]. The application of continuous-flow systems is frequently found in chemistry, and is beginning to have a significant impact on the way

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

• be made. Keywords: cycloaddition; flow chemistry; photocatalysis; photochemistry; photooxygenation; Introduction The use of ultraviolet light to carry out bond-forming reactions in synthetic organic chemistry has a long history dating back to the mid-19th century. The observation by Trommsdorff [1

• not generally think photo-retrosynthetically. As a result potentially shorter and more efficient synthetic routes to complex organic molecules, as well as access to new molecular space have long been avoided by mainstream synthetic chemists. Flow to the rescue? Over the last 15 years flow chemistry

• of bulk solutions, which combined with the extremely short lifetime of singlet oxygen means that lengthy irradiations are often required. These issues can be overcome through the use of continuous-flow chemistry: reactions performed in this manner have only a small amount of oxygenated solvent and

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

• . Keywords: azides; chemical diversity; flow chemistry; heterocycles; laser; micro reactor; Introduction Classical combinatorial chemistry [1][2] approaches usually aim at the synthesis of multi-milligram amounts of new compounds to extend screening decks used in multiple screening campaigns [3]. An

• alternative method enabled by the maturing microreaction technology and the use of flow chemistry [4][5][6] is the integration of synthesis and screening in one integrated lab-on-a-chip approach [7]. Using this methodology we have integrated photochemistry in a miniaturized reaction setup to enable

• 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

Continuous proline catalysis via leaching of solid proline

• Suzanne M. Opalka,
• Ashley R. Longstreet and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2011, 7, 1671–1679, doi:10.3762/bjoc.7.197

• . Keywords: aminoxylation; flow chemistry; heterogeneous catalysis; packed-bed microreactor; proline/thiourea catalysis; Introduction Continuous flow chemistry [1][2][3], performed in small dimension tubing or channels, differs from batch chemistry in that mixing and heat transfer are significantly faster

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

• 2NY, UK 10.3762/bjoc.7.194 Abstract Herein we describe the application of a monolithic triphenylphosphine reagent to the Appel reaction in flow-chemistry processing, to generate various brominated products with high purity and in excellent yields, and with no requirement for further off-line

• purification. Keywords: Appel reaction; bromination; flow chemistry; solid-supported reagent; triphenylphosphine monolith; Introduction Flow chemistry is well-established as a useful addition to the toolbox of the modern research chemist, with advantages accrued through increased efficiency, reproducibility

• ideal for use in a flow-chemistry setup. Elemental analysis showed an approximate loading of 1.87 mmol of phosphorus per gram, giving a calculated loading of 4.68 mmol of phosphorus per monolith, which is comparable to commercially available triphenylphosphine resins. Loading the monolith The monolith

Continuous-flow enantioselective α-aminoxylation of aldehydes catalyzed by a polystyrene-immobilized hydroxyproline

• Xacobe C. Cambeiro,
• Rafael Martín-Rapún,
• Pedro O. Miranda,
• Sonia Sayalero,
• Esther Alza,
• Patricia Llanes and
• Miquel A. Pericàs

Beilstein J. Org. Chem. 2011, 7, 1486–1493, doi:10.3762/bjoc.7.172

• alternative for improving the productivity of catalytic species results from the implementation of heterogenized catalysts in continuous-flow reactors. Flow chemistry has experienced a very important development in the last ten years as an emerging technology for organic synthesis [51][52][53][54][55][56][57

• ][58][59][60][61][62][63][64][65][66]. It offers as its main advantages facile automation and excellent heat and mass transfer, rendering the scale-up of a process a trivial task, in contrast with the obstacles always met in the scale-up of batch processes [67][68][69][70][71]. The combination of flow

• chemistry with solid-supported catalysts allows the advantages inherent to both technologies to be added together. Thus, the physical immobilization of the catalyst in a packed-bed reactor allows it to be submitted constantly to the reaction conditions, avoiding possible degradation of the catalyst during

Multistep flow synthesis of vinyl azides and their use in the copper-catalyzed Huisgen-type cycloaddition under inductive-heating conditions

• Lukas Kupracz,
• Jan Hartwig,
• Jens Wegner,
• Sascha Ceylan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2011, 7, 1441–1448, doi:10.3762/bjoc.7.168

• requires further optimization. This and other examples [11][12][13] principally demonstrate that flow chemistry is an ideal enabling technology [14] for generating and utilizing hazardous azido reagents because only small amounts are generated at a time and are subsequently consumed in situ. The other

• benefits of flow chemistry, when working with highly reactive reagents, are the better heat-transfer characteristics due to a larger surface-to-volume ratio, as well as the increased mixing efficiency [15][16][17][18][19][20][21][22][23][24]. To practically eliminate the generation of explosive iodine

The Eschenmoser coupling reaction under continuous-flow conditions

• Sukhdeep Singh,
• J. Michael Köhler,
• Andreas Schober and
• G. Alexander Groß

Beilstein J. Org. Chem. 2011, 7, 1164–1172, doi:10.3762/bjoc.7.135

• yields. We have used a flow chemistry system to promote the Eschenmoser coupling under enhanced reaction conditions in order to convert the demanding precursors such as S-alkylated secondary thioamides and thiolactames in an efficient way. Under pressurized reaction conditions at about 220 °C, the

• desired Eschenmoser coupling products were obtained within 70 s residence time. The reaction kinetics was investigated and 15 examples of different building block combinations are given. Keywords: activation energy; episulfide; flow chemistry; keto imine; kinetics; S-alkylation; sulfide contraction

• minimum residence time. For small scale synthesis flow chemistry is of great advantage to realize these conditions on the laboratory bench safely [18]. Results and Discussion For the reaction optimization we have focused on a straightforward procedure that finally prevents the isolation of the S-alkylated

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

• different reactions can be carried out successfully using simple protocols. Keywords: diaryliodonium compounds; electrochemistry; flow chemistry; microreactor; Introduction Electrochemical reactions offer a clean route to the formation of anion and cation radical species from neutral organic molecules

Chemistry in flow systems II

• Andreas Kirschning

Beilstein J. Org. Chem. 2011, 7, 1046–1047, doi:10.3762/bjoc.7.119

• did not live up to the original hype. No one can predict the future impact of flow chemistry, but it is an enabling technology that was introduced to the laboratories of synthetic organic chemists around ten years ago and has flourished for about half a decade now. We can draw a parallel with

• highlight three areas. First of all, we have the application to photochemistry, which has the chance of experiencing a renaissance particularly in an industrial environment. Second, flow chemistry lends itself naturally to the synthesis and direct application of reactive intermediates or reactive reagents

• reactor is exposed to these extreme conditions. You are invited to explore this Thematic Series and you will see contributions from some of the most prominent and creative groups in the world working in the field of flow chemistry. Not surprisingly this series has significantly increased in size since the

Continuous flow hydrogenation using polysilane-supported palladium/alumina hybrid catalysts

• Hidekazu Oyamada,
• Takeshi Naito and
• Shū Kobayashi

Beilstein J. Org. Chem. 2011, 7, 735–739, doi:10.3762/bjoc.7.83

• . The catalyst retained high activity for at least 8 h under neat conditions. Keywords: flow chemistry; hydrogenation; polysilane; palladium; reduction; Findings Catalytic hydrogenation is one of the most important methods for the reduction of C–C double and triple bonds, and other functional groups

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

• order to conduct highly exothermic reactions safely [1][2][3][4][5][6][7][8][9]. More recently, following the concepts of “Process Intensification” and “Novel Process Windows” [10][11][12], flow chemistry executed in high-temperature and/or high-pressure regimes have become increasingly popular [13

• effects in flow chemistry are also discussed. Results and Discussion Flow degradation of 5-benzhydryl-1H-tetrazole As a model system for tetrazole formation the microwave-assisted cycloaddition of diphenylacetonitrile (1) with NaN3 was studied (Scheme 1). After considerable experimentation [25] an optimum

Looking forward to volume six

• Jonathan Clayden

Beilstein J. Org. Chem. 2010, 6, No. 1, doi:10.3762/bjoc.6.1

• way within the journal, these papers can be viewed together using the “thematic series” tool on the website. Recent series have covered the topical themes of flow chemistry [1], supramolecular chemistry [2] and liquid crystals [3], and further series on carbohydrate chemistry and on organofluorine

Continuous flow enantioselective arylation of aldehydes with ArZnEt using triarylboroxins as the ultimate source of aryl groups

• Julien Rolland,
• Xacobe C. Cambeiro,
• Carles Rodríguez-Escrich and
• Miquel A. Pericàs

Beilstein J. Org. Chem. 2009, 5, No. 56, doi:10.3762/bjoc.5.56

• transferred to the reacting carbonyl compound. It is to be mentioned that other strategies for the preparation of mixed alkylarylzinc species from cheap organometallic reagents have been developed in recent times and could probably be also used for the same purpose [33][34][35]. Flow chemistry [36][37][38][39

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

Continuous flow based catch and release protocol for the synthesis of α-ketoesters

• Alessandro Palmieri,
• Steven V. Ley,
• Anastasios Polyzos,
• Mark Ladlow and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2009, 5, No. 23, doi:10.3762/bjoc.5.23

• impacting on the way we assemble molecules. Of these, flow chemistry technologies are becoming especially important [3][4][5][6][7][8][9][10][11][12][13][14]. For many years, our group [15][16][17][18][19][20][21][22] has been focussed on using immobilised systems [23][24][25][26][27][28][29] to more

• -ketoester product 4 by flowing aqueous acetic acid (step 4) through the in-line column. The overall route constitutes a new flow chemistry example of the catch-react-and-release concept that we have used successfully in other synthesis programmes [101][102][103]. The nitroolefinic esters 1 were originally

• Uniqsis FlowSyn™ unit to achieve multi-step organic synthesis under continuous flow-chemistry conditions. This was accomplished by adapting the device to incorporate immobilised reagents packed in flow tubes, enabling clean transformations without recourse to conventional product work-up or purification

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

• materials as solid-supports for catalysts and reagents have been found to be particularly well-suited for flow chemistry [34][35][36]. These rigid structures have large surface areas, leading to improved mass-transfer between the supported catalyst with the liquid phase and do not suffer from large pressure

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

• functionalized with a range of catalysts and works well as packing material for flow chemistry [39]. In this report, we demonstrate the immobilization of TEMPO and its use in a flow system using the Anelli-Montanari protocol for the oxidation of primary and secondary alcohols [30][40]. Our simplified reactor is