Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• in a continuous-flow reactor using five different monosaccharides and one disaccharide. We showed that this flow set up provides excellent conversion rates with several substrates. All monosaccharides were shown to react under the same conditions with equivalent conversion rates, whereas the

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

• . Strauss first demonstrated in 1994 that by combining microwave-heating technology with continuous flow processing, problems with the limited penetration depth of microwave irradiation and the physical restrictions of a standing wave cavity could be overcome [14]. A continuous flow reactor has the

• microwave flow chemistry, is realizing its potential towards the next evolutionary step in synthetic chemistry [43]. In 2005 we described a new continuous flow reactor design for microwave-assisted synthesis that operates in the optimum standing-wave cavity of a proprietary instrument [44]. The principal

• synthetic procedures to a continuous flow processing regime in a microwave flow reactor seemed highly feasible to access pyridine derivatives in a single step. Results and Discussion Synthesis of pyridines in a continuous flow reactor Many of our previous studies on the synthesis of pyridines in a

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

• backbone functionalized phenanthrenes and helicenes of various sizes in good yields. Keywords: continuous-flow reactor; flow chemistry; helicenes; light-driven cyclization reaction; photocyclization; stilbenes; Introduction Phenanthrenes are versatile intermediates toward polycyclic aromatic hydrocarbons

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

• to the flow unit In interfacing our Raman spectrometer with a continuous-flow reactor, our objective was to use a similar approach to that which proved successful when using microwave heating. Borosilicate glass is essentially “Raman transparent”. Therefore reactions could be monitored by placing a

• the spectrometer almost without any loss of light. The optimum distance of the light-pipe to the outside wall of the reaction vessel was found to be approximately 0.5 mm. Moving to our continuous-flow reactor, we decided to place the spectroscopic interface just after the back-pressure regulator

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

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

• ) tubing (3.1 mm o.d., 2.7 mm i.d.) was used to construct a simple but highly effective single-pass continuous-flow reactor (Figure 3). This reactor demonstrated for the first time how synthetic organic photochemical reactions can be scaled up in a traditional laboratory fume hood to produce multigram

• a continuous flow reactor consisting of an Ehrfeld Photoreactor XL driven by a custom built bank of four 8 W low-pressure lamps. The intramolecular cycloaddition of cyclopentenone 92 (Scheme 31) was optimised by varying the reactor channel thickness (20–90 μm), concentration and flow rate. Under

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

• polymer. With the most efficient resin (1a), ca. 30 mmol of product was isolated per mmol of resin for every flow experiment (5 h), thus meaning a four-fold improvement with respect to the batch process. Conclusion In summary, a packed-bed continuous-flow reactor was designed and implemented, based on

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

• (Scheme 2) was investigated under continuous-flow conditions. As the continuous-flow reactor enables the reaction chamber to be maintained at the reaction temperature (once the steady state is reached) time is not wasted for heating and cooling of the stopped-flow “batches”. Consequently, the system has

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

• /liquid–liquid/liquid continuous flow process. No examples of gas/liquid–liquid/liquid processes involving direct fluorination as the first stage of a continuous flow procedure have been reported previously. Results and Discussion After some development work, a continuous flow reactor for sequential gas

• purging the continuous flow reactor apparatus [29] (Figure 1) with nitrogen, a 10% mixture of fluorine in nitrogen (v:v) was passed through the flow reactor via Input A at a prescribed flow rate that was controlled by a gas mass flow controller (Brooks Instruments). The flow reactor was cooled by an

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

• continuous flow reactor and an image of the top of the column are shown in Figure 1. A high performance liquid chromatography (HPLC) pump was used to feed the substrate into the central hole in the top of the column, which was filled with the Pd/(PSi–Al2O3) catalyst. Hydrogen gas was introduced into the six

• leaching was detected (ICP). Further studies of the application of these systems to large-scale production are now in progress. Experimental The continuous flow reactor system comprised the following devices (Figure 1): HPLC pump: Shimadzu LC-6AD or Eyela 301. Mass flow controller: Lyntec MC-3000E and RP

• , CDCl3) δ 7.46–7.50 (m, 2H), 7.60–7.63 (m, 1H), 8.12–8.14 (m, 2H). Schematic diagram of the continuous flow reactor (left) and the column top (right). Hydrogenation of ethyl cinnamate. Hydrogenation of trans-stilbene and trans-chalcone. Hydrogenation of nitrobenzene and deprotection of the Cbz group

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

• tetrazole decomposition in the stainless steel coils is connected to metal contamination as a result of steel corrosion phenomena, a series of inductively coupled plasma mass spectrometry (ICPMS) experiments were performed. ICPMS analysis of a NMP/AcOH/H2O (5:3:2) mixture pumped through the continuous flow

• reactor at 220 °C (residence time 5 min) revealed that a range of metals are released from the coil under these conditions. Especially Fe (up to 113 ± 6 mg/L) but also Ni (up to 21.0 ± 1.0 mg/L), Cr (up to 32.3 ± 1.5 mg/L) and Mn (up to 4.9 ± 0.3 mg/L) were found in the processed solvent (Table S1

Kinetics and mechanism of vanadium catalysed asymmetric cyanohydrin synthesis in propylene carbonate

• Michael North and
• Marta Omedes-Pujol

Beilstein J. Org. Chem. 2010, 6, 1043–1055, doi:10.3762/bjoc.6.119

• achieved at atmospheric pressure and room temperature [74][75][76][77], or in a gas-phase continuous flow reactor [78], thus facilitating the use of waste carbon dioxide in this process [79]. In this paper we give full details of the use of catalyst 2 in propylene carbonate, and describe kinetic studies

From discovery to production: Scale- out of continuous flow meso reactors

• Peter Styring and
• Ana I. R. Parracho

Beilstein J. Org. Chem. 2009, 5, No. 29, doi:10.3762/bjoc.5.29

• water in the solvent, and in the flow system. Even though water is used to equalise the pressure in the flow system, the reactor is protected from the pumping system using a self-indicating silica gel drying tube that is regularly recharged. Mini-Continuous Flow Reactor Previous work carried out by

• , with a 67% yield of 4-methoxybiphenyl being achieved using phenylmagnesium bromide. As the residence time has an important effect on the product yield, and with the aim of scaling out the same reaction in the parallel capillary reactor, the reaction was carried out in the continuous flow reactor at

• different flow rates. The motivation was to investigate the effect of the residence time of the reagents within the catalyst bed on the coupling process. The mean residence time in a continuous flow reactor is also assumed to be the reaction time. Therefore the reaction was performed at different flow rates

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

• lipase B, Novozym® 435, in a preliminary investigation into the development of a continuous flow reactor capable of performing the chemo-enzymatic oxidation of alkenes in high yield and purity, utilising the commercially available oxidant hydrogen peroxide (100 volumes). Initial investigations focussed

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

• chemical syntheses [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54]. In this work we report the use of the Uniqsis FlowSyn™ continuous flow reactor [55] (Figure 1) to effect a flow-based preparation of α-ketoesters. The key feature of this process is the application of a catch and

• . The overall process delivers synthetically useful α-ketoester products in high purity from various nitroalkane inputs and paves the way for more extended reaction sequences. The Uniqsis FlowSyn™ continuous flow reactor comprising of a column holder and heating unit (A) and the reactor coil (B). A

Polyionic polymers – heterogeneous media for metal nanoparticles as catalyst in Suzuki–Miyaura and Heck–Mizoroki reactions under flow conditions

• Klaas Mennecke and
• Andreas Kirschning

Beilstein J. Org. Chem. 2009, 5, No. 21, doi:10.3762/bjoc.5.21

• excellent. Aryl chlorides did not react with catalyst 3 under flow conditions. To fully explore the potential of polyionic gel 3 its reusability was investigated next. The Suzuki reaction of 4-bromotoluene (6) with phenylboronic acid (10) served as model reaction. After each reaction the continuous flow

• reactor was regenerated by pumping a solution of DMF/water (10:1, 40 mL) through the reactor before the next run was initiated (Figure 2). The palladium particles inside the flow reactor showed excellent stability without loss of activity after the tenth run. Palladium leaching was determined to be about

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

• co-workers have designed a continuous-flow reactor system, PASSflow [40], based on the use of a functionalizable monolithic rod derived from a glass/polymer composite. This device was used for the dynamic kinetic resolution of epibromohydrin 32, using a monolith reactor functionalized with a chiral

• -mL continuous flow reactor when 221 g of alcohol 48 were processed, providing consistent results over a period of 3 days. An interesting example of a chiral separation using a cross-linked polymeric acylase aggregate immobilized in a microreactor was reported by Maeda and coworkers [57]. Taking

• )- 54 with immobilized lipase in a continuous scCO2- flow reactor. Enantioselective separation of Acetyl-D-Phe in a continuous flow reactor. Acknowledgements We thank the ETH Zürich, Astra Zeneca, and Merck, Sharpe & Dohme for generous financial support of the microreactor program in the Seeberger