Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• interconnected photocatalytic cycles as the hydrodehalogenation, an aryl radical 2• is formed via successive PET and C(sp2)–X bond cleavage (Figure 17B). Carbon monoxide, introduced to the reaction mixture by a tube-in-tube reactor, traps the aryl radical to generate the acyl radical 23 (Figure 17B

Honeycomb reactor: a promising device for streamlining aerobic oxidation under continuous-flow conditions

• Masahiro Hosoya,
• Yusuke Saito and
• Yousuke Horiuchi

Beilstein J. Org. Chem. 2023, 19, 752–763, doi:10.3762/bjoc.19.55

• mixer needs to be developed to enable more robust aerobic oxidation under continuous-flow conditions. A static mixer is generally used by inserting it into a tube reactor. In the gas-liquid biphasic flow reaction, the static mixer has to be inserted into the full range of the tube reactor to maintain

• tube reactor, a tube reactor with a static mixer and the honeycomb reactor (Scheme 2, Figure 3 and Table 3). The ratio of flow rates to internal volumes was unified in all the reactors. In the standard tube reactor, slug-flow was formed, and the conversion was 47% (Table 3, entry 1). To evaluate the

• reaction rate for increasing the flow rate, the reaction solution was passed through the standard tube reactor three times (Table 3, entry 2). The internal vortex was strengthened by increasing the flow rate, and the mixing efficiency was improved to give a higher reaction rate (67%). In the tube reactor

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• prepared in situ in the flow tube reactor, as the aqueous solution containing β-CD (1) and NaOH (1.5 equiv) was introduced into the reactor at twice the flow rate as the solution of TsCl in THF (Scheme 1). In this way, twice as many equivalents of TsCl were required compared to the general 1.3 equivalents

Continuous flow synthesis of azobenzenes via Baeyer–Mills reaction

• Jan H. Griwatz,
• Anne Kunz and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2022, 18, 781–787, doi:10.3762/bjoc.18.78

• part in Supporting Information File 1). After mixing, the solution was passed through a tube reactor, in which the temperature as well as the residence time can be easily modified. Afterwards the respective reaction mixture was collected and analyzed (Figure 1). In order to optimize the reaction, both

• cyclohexane to the reaction mixture after the tube reactor (Figure 3). The reaction solution with cyclohexane was continuously fed into a separating funnel containing brine. After phase separation, drying of the organic phase with MgSO4, and evaporation of the solvent, AB (1a) could be obtained in 98% yield

• be prepared in high yields and large quantities which opens new possibilities for applications of AB as molecular materials in general. Flow setup for optimization of the Baeyer–Mills reaction with aniline (2a) and nitrosobenzene (3). In this setup the temperature of the tube reactor as well as the

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• oxidant (Scheme 8B) [39]. The process is performed at 120 °C at 10 bar with a residence time of 6 min, and catalyzed homogenously utilizing the established “MC-system” (manganese/cobalt/bromide) in a heated tube reactor. Remarkably, acetophenone is obtained in a good yield of 66% and in 96% purity without

• 240 °C in one tube reactor, the reaction gives incomplete conversion and the yield of coumarin (46) drops to 21%. The authors proposed that under these conditions the reaction proceeds via the Perkin process, which is significantly slower than the O-acylation/aldol sequence [42]. An odorant that is

• and unactivated alkanes, including the transformation of isodihydrobenzofuran (47) to phthalide (50, Scheme 11) [44]. In this reaction, the decatungstate anion is activated by irradiation in a 3D-printed tube reactor using LED light with a wavelength of λ = 365 nm. It is assumed, that the photoexcited

Rapid gas–liquid reaction in flow. Continuous synthesis and production of cyclohexene oxide

• Kyoko Mandai,
• Tetsuya Yamamoto,
• Hiroki Mandai and
• Aiichiro Nagaki

Beilstein J. Org. Chem. 2022, 18, 660–668, doi:10.3762/bjoc.18.67

• ratio of aldehyde and oxygen to 1:9. The liquid and gas phases were combined at a T-shaped mixer with a 1 mm inner diameter and flowed through a stainless-steel tube reactor immersed in heated silicon oil for reaction temperature control. The inner pressure was maintained at 0.9 MPa using a back

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• including protocols with 24 h experiments under continuous-flow conditions using a very simple home-made photoreactor (segmented flow – PFA tube reactor). We have compared the same reaction conditions in both batch (7–20% yield) and continuous-flow conditions (up to 82% yield) and thus showed a very

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• Ar–Csp3, Ar–Csp2 and Ar–Csp bond-forming reactions. The use of a photochemical flow reactor, consisting of a polyfluorinated tube reactor wrapped around a 500 W Hg lamp, allowed to overcome batch limitations paving the way for metal-free arylation reactions via phenyl cations. Derivatives 14a–g were

Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation

• Olga C. Dennehy,
• Valérie M. Y. Cacheux,
• Benjamin J. Deadman,
• Denis Lynch,
• Stuart G. Collins,
• Humphrey A. Moynihan and
• Anita R. Maguire

Beilstein J. Org. Chem. 2016, 12, 2511–2522, doi:10.3762/bjoc.12.246

• coiled tube reactor at 120 °C. The high surface area–volume ratio of tubular flow reactors is ideal for such rapid temperature transitions. It was noted that a relatively short residence time of only 20 min could be used, with a longer time of 50 min offering only a modest improvement on the reaction

Catalytic Chan–Lam coupling using a ‘tube-in-tube’ reactor to deliver molecular oxygen as an oxidant

• Carl J. Mallia,
• Paul M. Burton,
• Alexander M. R. Smith,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1598–1607, doi:10.3762/bjoc.12.156

• amounts of copper catalyst to be used [15][16]. Based upon our previous experience of using the reverse “tube-in-tube” reactor with other gases, it was decided that oxygen would be delivered via this reactor set-up (Figure 1). Results and Discussion In our initial screening, four different organic

• acid. A column of QP-DMA, a polymer-supported tertiary amine base, was placed in-line after the “tube-in-tube” reactor (Figure 1). It was found that this was sufficient to remove the majority of boronic acid without affecting the yield of the product (Figure 3). Ultimately as the products were required

• modification can reliably deliver 0.216 g h−1 of 19 at 81% isolated yield. Conclusion The use of flow chemistry for the C–N coupling through a catalytic Chan–Lam reaction has allowed for a safe and efficient introduction of oxygen through a reverse “tube-in-tube” reactor. Optimisation of the reaction

Flow carbonylation of sterically hindered ortho-substituted iodoarenes

• Carl J. Mallia,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1503–1511, doi:10.3762/bjoc.12.147

• the gases in the liquid phase. In our work a reverse “tube-in-tube” reactor [31][32][33] was used to deliver the carbon monoxide to the reaction (Figure 3), as this was shown to be more efficient than an alternative plug flow system (Scheme 1) when evaluated on iodobenzene (2). The “tube-in-tube” gas

• of X-ray structure; C) ball and stick representation of X-ray structure showing the tolyl group only; D) topside view of X-ray structure [18]. Reverse “tube-in-tube” reactor. Phosphine ligands used for the ortho-carbonylation reaction. X-ray structure of substrate 33. Comparison of plug flow reactor

• carbonylation (left) and “tube-in-tube” reactor carbonylation (right). Schematic diagram of the flow process. The batch carbonylation of 2-chloro-1-iodobenzene in conventional lab (top) and using a Parr autoclave in high pressure lab (bottom). Structures of ortho-substituted carboxylic acids prepared via a

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

• solutions of N,N-dialkyl-N-chloramines produced continuously will enable their use in tandem flow reactions with a range of nucleophilic substrates. Keywords: amine; biphasic; chloramine; chlorination; continuous flow chemistry; CSTR; static mixer; sodium hypochlorite; tube reactor; Introduction N

• transfer reasons discussed above, and possibly for electronic and steric reasons as well. The tube reactor did not conveniently allow sufficient residence times for full conversion of amine to chloramine to be achieved, and in such cases a continuous stirred tank reactor (CSTR), able to provide longer

• and 2) proceeded with high yields under short reaction times using the static mixers. N-chloro-N-methyl-p-toluenesulfonamide and N-chloro-N-benzylmethanamine proceeded with good yields in both the tube reactor and CSTR, however, for the tube reactor 1.5 equiv NaOCl were required for complete reaction

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

• and commercialisation of a laboratory based tube-in-tube reactor by the Ley group in 2009 changed the playing field and popularised the wider use of gases and volatile components. The design of the tube-in-tube system is based on a semipermeable Teflon AF2400 tubing (1 mm o.d., 0.8 mm i.d.) being

• intermediate passes into a tube-in-tube reactor, where carboxylation takes place furnishing the lithium carboxylate 129. Excess carbon dioxide is subsequently removed using a degassing tube before reacting species 129 with a further stream of n-BuLi to induce cyclisation to dibenzosuberone (130) in a short

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

• applicator for continuous-flow organic chemistry [17][18]. The current setup is depicted in Figure 1 and features a HPLC pump, a generator, a reactor cavity, an applicator and a Ø (ID) 3 mm × 200 mm borosilicate glass tube reactor. Nonresonant mode applicators has the advantage of avoiding hot and cold spots

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

• mixing of reagents, boosting reaction rates, and safe handling of reactive intermediates. Using a commercial continuous-flow tube reactor [19], we have already demonstrated multigram synthesis of fullerene derivatives by cycloaddition reactions [11] as well as rapid conjugated-polymer synthesis using

• reaction temperatures used. To demonstrate the flow synthesis of P3HT from 2,5-dibromo-3-hexylthiophene (1), the Grignard metathesis step was performed in the tube reactor followed by the addition of the Ni(dppp)Cl2 catalyst for the polymerization (Scheme 2). In this telescoped process, the thiophene

• monomer-to-catalyst ratio with variations in reagent concentration and flow rates. This methodology enables the controlled synthesis of conjugated polymers in flow exclusively by the adjustment of the feed of monomer and initiator into the tube reactor. The major challenge in this study was to find

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

• , such as the length of tubing used and the residence time required to effect a complete reaction. For subsequent work using oxygen gas, we moved to a more elegant but still simple tube-in-tube reactor setup [79]; in this case the oxidation of a lilac solution of vanadium(II) was used to indicate the

• presence of oxygen in the solvent stream. With increased concentrations of oxygen in the reactor atmosphere, this oxidation proceeded with faster rates (Figure 18b). Having determined that the gaseous reagents were passing through the semipermeable tubing, we were able to use the tube-in-tube reactor for

• 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

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

• tube reactor containing a glass column packed with 1 g of proline, and a low-temperature 10 mL PFA coil-tube reactor in which each reagent stream could be precooled prior to mixing (Figure 2). As we demonstrate below, the success of our experiments depended on the ability of the system to heat, or cool

• packed with 1 g of proline. B) The column is then placed in-line with a 10 mL PFA coil-tube reactor. C) The components are connected to HPLC pumps for solvent and reagent inputs. The reactor is controlled by a computer in order to program the timing of the reagent and solvent inputs and fraction

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

• ]. Continuous epoxidation of 1,7-octadiene (70) to (R)-7-epoxyoctene (72) by a strain of Pseudomonas oleovorans in a closed-gas-loop bioreactor (CCGLB). R: Reductase; Fe: Rubredoxin [51]. Oxidation of styrene (73) to (S)-styrene oxide (74) in a continuously operated biofilm tube reactor containing cells of

Oxidative cyclization of alkenols with Oxone using a miniflow reactor

• Yoichi M. A. Yamada,
• Kaoru Torii and
• Yasuhiro Uozumi

Beilstein J. Org. Chem. 2009, 5, No. 18, doi:10.3762/bjoc.5.18

• with a flow rate of 4.0 μl/min each by using syringe pumps from the individual inlets. The mixed solution passed through a PTFE tube reactor (length = 50 mm) at 80 °C, and then was quenched with 30% aq Na2S2O3 solution injected into the flow tube with a flow rate of 4.0 μl/min. The resulting organic