Continuous formation of N-chloro-N,N-dialkylamine solutions in well-mixed meso-scale flow reactors

• A. John Blacker and
• Katherine E. Jolley

Beilstein J. Org. Chem. 2015, 11, 2408–2417, doi:10.3762/bjoc.11.262

• A. John Blacker Katherine E. Jolley Institute of Process Research and Development, School of Chemistry and School of Chemical and Process Engineering, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, Leeds, UK 10.3762/bjoc.11.262 Abstract The continuous flow synthesis of a range of organic

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

• rely on convective heat transfer. Although this is rapid for small reactor dimensions as the scale of the device increases the efficacy of the heating rapidly falls. The Kirschning group has introduced inductive heating (IH) as an energy stimulus for continuous flow synthesis [102][103]. In this

• concept or piece of equipment that is better suited to performing an otherwise challenging task. One aspect of continuous flow synthesis for which little progress was made for a long time concerned the way in which reagents streams were delivered into the reactors. In much of the early flow chemistry work

Continuous flow nitration in miniaturized devices

• Amol A. Kulkarni

Beilstein J. Org. Chem. 2014, 10, 405–424, doi:10.3762/bjoc.10.38

• initial development and demonstration of the continuous flow synthesis using miniaturized devices or microreactors took place in academia and research institutions. The benefits of the approach are particularly evident for highly exothermic reactions and for reactions involving unstable intermediates

• step to isolate the product. However, since the large-scale synthesis of nitropyrazoles is not a safe reaction under batch conditions, the continuous flow synthesis is the process of choice. Henke and Winterbauer [46] reported a corrosion resistant microreactor built up of PTFE and tantalum for the

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

• fluorine chemistry. Meanwhile, flow microreactor synthesis, the use of microfluidic devices, has emerged as a new method for producing chemical substances with high efficiency [11][12][13]. Now, the introduction of continuous-flow synthesis technique to laboratory synthesis represents a highly useful and

• conducted in one flow by adding the reagents at different places in continuous-flow synthesis [18][19][20][21][22][23][24][25]. This review deals with the successful examples on synthesis and reactions of fluorine-containing molecules by the use of flow microreactor systems. Useful applications using flow

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

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

• . 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

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

• demonstrate the high reproducibility of the system. FLLEX module Having established a microreactor protocol for the continuous-flow synthesis of EDA, the next issue was to separate the product from the biphasic system in which it was collected. In order to increase safety and decrease the hold-up of EDA, the

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

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

• Suzuki–Miyaura and Stille coupling [12]. In this study, the continuous-flow synthesis of P3HT is examined. Distinct from a recent report of P3HT synthesis in a droplet-based microreactor [20], development of the flow synthesis is described in detail and controlled polymerization of P3HT, both in terms of

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

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

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

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