Temperature measurements with two different IR sensors in a continuous-flow microwave heated system

• Jonas Rydfjord,
• Fredrik Svensson,
• Magnus Fagrell,
• Jonas Sävmarker,
• Måns Thulin and
• Mats Larhed

Beilstein J. Org. Chem. 2013, 9, 2079–2087, doi:10.3762/bjoc.9.244

• temperature measurements in continuous-flow synthesis appears less attractive. Although providing a direct measurement of the temperature in the reactor it is not robust enough for daily use and handling, especially under reaction conditions that may be relevant in organic synthesis applications [22][23

• microwave absorbing solvents). In conclusion, we believe this investigation might be of interest for the future development and understanding of microwave heated continuous flow synthesis. Instrument setup. (a) Setup of system with temperature measurement by IR sensor 1. (b) Illustration of temperature

Flow synthesis of a versatile fructosamine mimic and quenching studies of a fructose transport probe

• Matthew B. Plutschack,
• D. Tyler McQuade,
• Giulio Valenti and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 2022–2027, doi:10.3762/bjoc.9.238

• in the presence of potential quenchers. This increased understanding will be critical when probing uptake into various biological systems where cell staining techniques or supplemental amino acids are used. Herein, we report an efficient flow synthesis of amine 3 that enabled an increase in scale as

• NBDM quenching was observed even at sugar concentrations as high as 100 mM. Conclusion In conclusion, we report the flow synthesis of the fluorescent fructose mimic NBDM. While we demonstrated for the first time that resin-supported nitrite ions can facilitate Tiffeneau–Demjanov rearrangements, we

• . Continuous flow synthesis of the key intermediate 1-amino-2,5-anhydro-D-mannose (3). Batch versus flow comparison. Supporting Information Supporting Information File 482: Experimental part. Acknowledgements Financial support from the Max Planck Society and the National Science Foundation (USA; CHE-1152020

Continuous flow photocyclization of stilbenes – scalable synthesis of functionalized phenanthrenes and helicenes

• Quentin Lefebvre,
• Marc Jentsch and
• Magnus Rueping

Beilstein J. Org. Chem. 2013, 9, 1883–1890, doi:10.3762/bjoc.9.221

• the efficiency of the transformation is no longer related to the scale [17][18][19][20][21]. Therefore, the development of an efficient protocol for the photocyclization of stilbene derivatives in flow would be of great interest. A recent contribution described the flow-synthesis of [5]helicene under

• . Photo-flow synthesis of [5]- and [6]helicenes. aFor experimental details see Supporting Information File 1. bReaction conditions: 1.1 equiv iodine, 20 equiv THF, UV-light, 2 h retention time. Scale up synthesis of the [5]helicene derivative 2o. Proof of principle and screening of reaction conditions

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

• process using microreactor and separation technology. Ethyl diazoacetate (1) can be synthesized in flow via different pathways. Bartrum et al. [18] published a flow synthesis of numerous diazo esters starting from the corresponding arylsulfonylhydrazones, where the diazo moiety was installed through

• generally be efficiently regenerated. In-line phase separation was thought to greatly enhance the usefulness of the EDA flow synthesis. Therefore, the outlet of the microreactor was directly connected to membrane-based phase separator to obtain EDA in the organic phase, which in principle can then be

• immediately used for either batch [13][15] or continuous-flow [16][17] follow-up reactions. Straightforward scale-up or scale-out of microreactor technology renders this method viable for industrial application. Results and Discussion Flow synthesis Ethyl diazoacetate (1) was synthesized from glycine ethyl

The application of a monolithic triphenylphosphine reagent for conducting Ramirez gem-dibromoolefination reactions in flow

• Kimberley A. Roper,
• Malcolm B. Berry and
• Steven V. Ley

Beilstein J. Org. Chem. 2013, 9, 1781–1790, doi:10.3762/bjoc.9.207

• reported by Ramirez et al. [41]. Formation of the triphenylphosphine monoliths. Functionalising the triphenylphosphine monolith to give the active Ramirez monolith using carbon tetrabromide. Flow synthesis of gem-dibromoolefins using the functionalised triphenylphosphine monolith. Flow synthesis of

Chemistry in flow systems III

• Andreas Kirschning

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

• chemical synthesis in the laboratory from a classical batch approach to continuous processes by using micro- and miniaturized flow reactors. In the past two decades this technology has seen a dramatic increase of visibility. Considering an analyses of the accompanied developments in flow synthesis one has

• from chemists and synthetic chemists will only advance the field of miniaturized flow synthesis if they are aware of the technical and engineering aspects. This includes the quest for developing analytical devices for online monitoring and feedback loops for optimising synthetic protocols. Several of

The rapid generation of isothiocyanates in flow

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 1613–1619, doi:10.3762/bjoc.9.184

• chemical transformation which typically eliminates the requirements for any conventional work-up or purification of the reaction stream. Keywords: chloroxime; dipolar cycloaddition; flow chemistry; flow synthesis; immobilised reagents; isothiocyanate; nitrile oxide; Introduction Flow based chemical

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• found in the literature for the Cu(I)-catalysed flow synthesis of triazoles. Heterogeneous Cu(I) sources are most popular, such as copper-in-charcoal (Cu/C) [49][50], solid supported Cu(I) species [51][52][53][54], and heated copper wirings [55][56][57][58], but a homogeneous technique has also recently

Controlled synthesis of poly(3-hexylthiophene) in continuous flow

• Helga Seyler,
• Jegadesan Subbiah,
• David J. Jones,
• Andrew B. Holmes and
• Wallace W. H. Wong

Beilstein J. Org. Chem. 2013, 9, 1492–1500, doi:10.3762/bjoc.9.170

• optimization of large area devices is costly and often impossible to achieve. Continuous-flow synthesis enables straight-forward scale-up of materials compared to conventional batch reactions. In this study, poly(3-hexylthiophene), P3HT, was synthesized in a bench-top continuous-flow reactor. Precise control

• : conjugated polymers; continuous-flow synthesis; controlled polymerization; flow chemistry; organic solar cell materials; Introduction Poly(3-hexylthiophene), P3HT, is the most investigated material in bulk heterojunction (BHJ) organic solar cells (OSC) [1]. The reasons for its dominance in the field include

• -flow synthesis methods offer several advantages over traditional batch methods [14][15][16][17][18]. The scale-up of reactions is not only straightforward in continuous processing, but there are also benefits in high reaction reproducibility through accurate parameter control, superior heating and

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

• the tube-in-tube reactor. In a recent publication describing the use of ammonia gas in flow synthesis [80], a reversed, “tube-in-tube” reactor configuration was employed whereby the gas was introduced into the semipermeable tubing, while the substrate passed through a second, outer, PTFE tube. This

• directly in another synthetic step. For example, in a recent multistep flow synthesis of branched aldehydes from aryl iodides [98], an in-line aqueous extraction step following an ethylene-Heck reaction allowed the intermediate styrene products to be carried directly into a subsequent downstream

• argon, and from which the solution of products is injected into a second palladium-catalysed gas/liquid reaction. This represents a major step towards a universal and sustainable in-line separation and purification module to enable the direct connection of multiple stages in a flow-synthesis procedure

Continuous-flow hydration–condensation reaction: Synthesis of α,β-unsaturated ketones from alkynes and aldehydes by using a heterogeneous solid acid catalyst

• Magnus Rueping,
• Teerawut Bootwicha,
• Hannah Baars and
• Erli Sugiono

Beilstein J. Org. Chem. 2011, 7, 1680–1687, doi:10.3762/bjoc.7.198

• and other heterocyclic compounds [61][62][63][64][65]. Consequently, the development of an efficient synthesis to obtain these valuable compounds attracted our interest. Thus, we decided to develop an efficient continuous-flow synthesis of α,β-unsaturated ketones starting from alkynes and aldehydes by

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

• beads related to the solvent employed. To circumvent some of the issues with bead-type supports, monoliths have been developed as replacements for use in continuous-flow synthesis. Monoliths are a single continuous piece of uniformly porous material prepared by precipitation polymerisation of a

• triphenylphosphine monolith by using carbon tetrabromide in a recycling process. Flow synthesis of bromides from alcohols by using the functionalised triphenylphosphine monolith. Bromides prepared from the corresponding alcohols by using the functionalised triphenylphosphine monolith. Supporting Information

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

• Lukas Kupracz Jan Hartwig Jens Wegner Sascha Ceylan Andreas Kirschning Institute of Organic Chemistry, Leibniz University Hannover, Schneiderberg 1b, 30167 Hannover, Germany 10.3762/bjoc.7.168 Abstract The multistep flow synthesis of vinyl azides and their application in the synthesis of

• Amberlyst A-26 [26]. Chemically, this reagent behaves like iodine azide (1), but in contrast it is not explosive and is storable for weeks without a substantial loss of activity [27]. In this report, we disclose the first two-step flow synthesis of vinyl azides based on functionalized polymers 5 and 8. The

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

• ® S1) was employed for the continuous flow synthesis of diaryl ethers at 195 °C and 25 bar, affording a reduction in reaction time from tens of minutes to 60 s when compared with a stopped-flow microwave reactor. Keywords: automated synthesis; continuous flow; microreactor; microwave; nucleophilic

• illustration of the reactor manifold used to evaluate the continuous-flow synthesis of 2-chloro-1-(4-methoxyphenoxy)-4-nitrobenzene (7) in the presence of DBU (6). Comparison of the results obtained in Labtrix® S1 with reported data generated in a microwave synthesiser. Screen shot from the Labtrix® S1 control

Efficient and selective chemical transformations under flow conditions: The combination of supported catalysts and supercritical fluids

• M. Isabel Burguete,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2011, 7, 1347–1359, doi:10.3762/bjoc.7.159

• the corresponding bulk ILs [109]. CALB supported on those SILLPs was shown to be an efficient and very stable catalyst for the continuous flow synthesis of citronellyl propionate in scCO2. The presence of a high IL/enzyme ratio is reflected in a high stabilization of the CALB in those systems. Thus

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

• -adamantanecarboxylic acid (2a) in a microflow system. Koch–Haaf reaction of 1b and 1c in a microflow system. Multigram scale flow synthesis of 1-adamantanecarboxylic acid (2a). Koch–Haaf reactions of adamantanols.a Acknowledgements The authors thank MCPT and NEDO for financial support of this work. IR acknowledges

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

• synthesis of diaryliodonium salts [22]. We describe herein a simple procedure for the flow synthesis of diaryliodonium salts using the electrochemical microreactor device described above. The products were obtained in good yields and only minimal work-up was required after the reaction. The reaction takes

• C16H18I, 337.0448; found, 337.0444. Electrochemical microreactor. Electrochemically generated N-acyliminium ions 1 and subsequent reactions. Electrolysis of furan. Kolbe electrolysis of phenylacetic acids 6 in flow. Synthesis of diaryliodonium salts 11 in flow. Products and yields in the electrochemical

Continuous gas/liquid–liquid/liquid flow synthesis of 4-fluoropyrazole derivatives by selective direct fluorination

• Jessica R. Breen,
• Graham Sandford,
• Dmitrii S. Yufit,
• Judith A. K. Howard,
• Jonathan Fray and
• Bhairavi Patel

Beilstein J. Org. Chem. 2011, 7, 1048–1054, doi:10.3762/bjoc.7.120

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

• environment [41], in combination with the use of a flow reactor that employed a standard Al heating block as a coil heater [25]. Using this set-up, a general and scalable method for the continuous flow synthesis of 5-substituted-1H-tetrazoles via the addition of HN3 to organic nitriles was developed [25]. For

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

• microwave ovens and this method as well as the application in organic flow synthesis. Experimental setup for heating tubular flow reactors by passing electric current directly through the reactor wall. The characteristic linear temperature profile along the reactor length is also given. Conversion as a

Gold film- catalysed benzannulation by Microwave- Assisted, Continuous Flow Organic Synthesis (MACOS)

• Gjergji Shore,
• Michael Tsimerman and
• Michael G. Organ

Beilstein J. Org. Chem. 2009, 5, No. 35, doi:10.3762/bjoc.5.35

• regioselective, and proceeds in good to excellent conversion. Keywords: benzannulation; flow synthesis; gold catalysis; microwave; thin metal film; Introduction Microwave-assisted organic synthesis (MAOS) has had a significant impact on organic and medicinal chemistry by dramatically shortening reaction times

The development and evaluation of a continuous flow process for the lipase- mediated oxidation of alkenes

• Charlotte Wiles,
• Marcus J. Hammond and
• Paul Watts

Beilstein J. Org. Chem. 2009, 5, No. 27, doi:10.3762/bjoc.5.27

• increasing productivity, biocatalyst lifetimes and exploring the potential of employing immobilised enzymes in industrial processes. Recent examples include the continuous flow enantioselective acetylation of a series of racemic secondary alcohols [27] and the continuous flow synthesis of alkyl esters [28

• then analysed by GC-MS, 1H and 13C NMR spectroscopy in order to characterise the epoxide and determine product purity. Enzyme stability To confirm the Novozym® 435 (4) was sufficiently stable to be used for the continuous flow synthesis of epoxides over extended periods of operation, two experiments

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

• and release; flow synthesis; α-ketoesters; mesoreactor; polymer supported reagents; Introduction Organic synthesis is changing rapidly owing to the discovery of processes that challenge current dogma and lead to the invention of new chemical reactions [1][2]. Likewise, new synthesis tools are

• purification. The average yield for the nitroolefins 1a–j prepared as described in Scheme 2 was approximately 60% by LCMS. Impurities were readily removed following immobilisation of nitroolefinic esters 1 on the QP-BZA resin. In addition, the flow synthesis of two representative compounds was undertaken to

• detailed image of the reactor coil is shown on the right. α-Ketoesters prepared and isolated yields. General procedure for the flow synthesis of α-ketoester products 4a–j. General procedure for the batch synthesis of nitroolefinic esters 1a–j. General procedure for the flow synthesis of nitroolefinic