Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• permeable membrane reactors [46][47][48], high-pressure reactors utilizing back pressure regulators [49][50][51], reactors with different heating and cooling modes (e.g., inductive heating [11][52], microwave [53][54][55] etc.) and many more, also very special reactors [56] with other difficulties that need

Graphitic carbon nitride prepared from urea as a photocatalyst for visible-light carbon dioxide reduction with the aid of a mononuclear ruthenium(II) complex

• Kazuhiko Maeda,
• Daehyeon An,
• Ryo Kuriki,
• Daling Lu and
• Osamu Ishitani

Beilstein J. Org. Chem. 2018, 14, 1806–1812, doi:10.3762/bjoc.14.153

• W high-pressure Hg lamp (SEN) was used as a light source, in combination with a NaNO2 solution as a filter to provide visible light irradiation (λ > 400 nm). The gaseous reaction products were analyzed using a gas chromatograph with a thermal conductivity detector (GL Science, Model GC323). The

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• its slow decomposition to pyrazole and CO2. Such ambiguous substitution effects are therefore worthy of further investigations. Photochemical reaction of sydnones with symmetrical alkynes In 1966 Krauch et al. [59] dealt with irradiation (using a high-pressure Hg lamp) of benzene or dioxane solutions

An alternative to hydrogenation processes. Electrocatalytic hydrogenation of benzophenone

• Cristina Mozo Mulero,
• Alfonso Sáez,
• Jesús Iniesta and
• Vicente Montiel

Beilstein J. Org. Chem. 2018, 14, 537–546, doi:10.3762/bjoc.14.40

• K) and high-pressure (even 350 atm). Even though the hydrogenation is performed using either homogeneous or heterogeneous catalysts to enhance chemical kinetics, a number of side reactions reduces the selectivity of the chemical reaction providing also complex and cost-ineffective work-up procedures

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• phenolic product 6 in high yield with unchanged N,N-dimethylaminomethyl group. The same result was obtained at high pressure (40 bar) and upon addition of formic acid for accelerating hydrogenolysis [21]. Obviously, and in contrast to earlier reports on related naphthol Mannich bases [20], the benzylamine

• converted amine 5 into methoiodide 7 by treatment with iodomethane. This salt was obtained in pure form in 78% yield by simply collecting the precipitate, and there was no indication of an undesired methylation of the ring nitrogen of the isoquinoline. High-pressure hydrogenolysis of 7 gave only minor

An efficient synthesis of 1,6-anhydro-N-acetylmuramic acid from N-acetylglucosamine

• Matthew B. Calvert,
• Christoph Mayer and
• Alexander Titz

Beilstein J. Org. Chem. 2017, 13, 2631–2636, doi:10.3762/bjoc.13.261

• , and NOESY experiments. Mass spectra were obtained on a Bruker amaZon SL for low resolution or on a Bruker maXis 4G HR-QTOF spectrometer for high resolution, and the data were analyzed using DataAnalysis (Bruker Daltonics, Bremen, Germany). High-pressure liquid chromatography (HPLC) was carried out on

Mechanochemical N-alkylation of imides

• Anamarija Briš,
• Mateja Đud and
• Davor Margetić

Beilstein J. Org. Chem. 2017, 13, 1745–1752, doi:10.3762/bjoc.13.169

• the environment could be achieved by the minimization of waste produced in the process, the employment of the more efficient reagents and catalysts and by the application of microwave [2], photochemical [3] or high pressure conditions [4], thus reducing reaction time and energy consumption. In recent

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• organic solvents has offered an entirely new paradigm for the soluble-supported synthesis of oligonucleotides. The underlying idea is that on passing the reaction mixture by high pressure through a membrane, small molecules pass through the membrane, while the support is too bulky to escape through the

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

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

• Carmen Moreno-Marrodan,
• Francesca Liguori and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• catalysis [103][104]. Monolithic reactors may surpass most drawbacks typical of packed-bed systems, including high pressure drops, low contacting efficiency, large distribution of residence times, formation of hot-spots or stagnation zones, which results in poorly controlled fluid dynamics, hence in low

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

• –polymide film hybrid for fabrication because this material offers exceptional physical toughness at low temperature and high pressure as well as chemical inertness. The most relevant aspect of this microreactor, concerns the 3D design of the mixing zone (Figure 2). The mixing efficiency was evaluated on

Continuous N-alkylation reactions of amino alcohols using γ-Al₂O₃ and supercritical CO₂: unexpected formation of cyclic ureas and urethanes by reaction with CO₂

• Emilia S. Streng,
• Darren S. Lee,
• Michael W. George and
• Martyn Poliakoff

Beilstein J. Org. Chem. 2017, 13, 329–337, doi:10.3762/bjoc.13.36

• heterogeneous catalyst at elevated temperature and/or pressure is employed [20][21][22][23][24][25][26][27][28]. As these reactions are mostly carried out in high pressure systems, they are particularly suitable for the use of supercritical solvents. Supercritical solvents are highly compressed and/or heated

• Aldrich and used as standards. 1d,e [50], 6 [51], 7 [52], and 11 [53] were identified as previously described in the literature. GC analysis was carried out using the following instrument and conditions: Online Shimadzu GC-2014 with a high pressure sample loop and an OPTIMA delta-3 column (30 m, 0.25 mm

• ID, 0.25 µm FT): hold 50 °C 4 min, ramp to 100 °C at 25 °C/min, ramp to 250 °C at 10 °C/min, hold for 2 min, pressure 132.1 kPa, purge 3.0 mL/min split ratio 40. The high pressure continuous set-up (Figure 3) employed in the described reactions consisted of a HPLC pump through which a solution of the

Diels–Alder reactions of myrcene using intensified continuous-flow reactors

• Christian H. Hornung,
• Miguel Á. Álvarez-Diéguez,
• Thomas M. Kohl and
• John Tsanaktsidis

Beilstein J. Org. Chem. 2017, 13, 120–126, doi:10.3762/bjoc.13.15

• flow reactor. The reaction was conducted at 160 °C. The product, a transparent, faintly yellow solution, was collected at the reactor outlet, after passing through a stainless steel Swagelok® R3A series adjustable high pressure valve. This valve was used as a back pressure regulator, in order to set

A new protocol for the synthesis of 4,7,12,15-tetrachloro[2.2]paracyclophane

• Donghui Pan,
• Yanbin Wang and
• Guomin Xiao

Beilstein J. Org. Chem. 2016, 12, 2443–2449, doi:10.3762/bjoc.12.237

• benzyl brominated product was obtained. This could be explained by the deactivating effect of the nitro group [16]. Therefore, a 100 W high pressure mercury lamp (‘solar’ light) was used to increase the formation of bromide radical in the repeated bromination experiment of 9. On this occasion the yield

Superelectrophilic activation of 5-hydroxymethylfurfural and 2,5-diformylfuran: organic synthesis based on biomass-derived products

• Dmitry S. Ryabukhin,
• Dmitry N. Zakusilo,
• Mikhail O. Kompanets,
• Anton A.Tarakanov,
• Irina A. Boyarskaya,
• Tatiana O. Artamonova,
• Mikhail A. Khohodorkovskiy,
• Iosyp O. Opeida and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2016, 12, 2125–2135, doi:10.3762/bjoc.12.202

• temperature for 1–24 h gives rise to 5-arylmethylfurfurals (yields of 17–91%) and 2-arylmethyl-5-(diarylmethyl)furans (yields of 10–37%). The formation of these two types of reaction products depends on the nucleophilicity of the arene. The same reactions under the action of acidic zeolites H-USY in high

• pressure tubes at 130 °C for 1 h result in the formation of only 5-arylmethylfurfurals (yields of 45–79%). 2,5-Diformylfuran (2,5-DFF) in the reaction with arenes under the action of AlBr3 at room temperature for 1 h leads to 5-(diarylmethyl)furfurals (yields of 51–90%). The reactive protonated species of

A flow reactor setup for photochemistry of biphasic gas/liquid reactions

• Josef Schachtner,
• Patrick Bayer and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2016, 12, 1798–1811, doi:10.3762/bjoc.12.170

• ], multiphasic reactions including solid-phase protocols [18], addition of gaseous reagents [19], high-pressure conditions [20], cascade conversions without intermediate work-up operations [21], as well as thin film, falling film [22], micro-channel [23], and tube-in-tube reactors [24][25] for reactions between

• are suitable for most applications. A low dead volume and a high pressure resistance are key characteristics of T mixers. However, careful optimization of the internal size, shape, and dead volume of the T-mixer directly affects the local concentrations of the reagents and thus can have dramatic

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

• -up, conducted in the departmental high pressure lab (HPL), was set up in a Parr autoclave using carbon monoxide at 15 bar and 110 °C for 2 hours. After purification, a yield of 87% for product 5 was obtained. This compares well with the flow protocol, however, the reaction “processing” time is in

• reality much longer due to the long cooling and heating times (4 h 15 min “processing” time, see experimental section in Supporting Information File 1 for more details). Also, the time required due to the extra precautionary measures needed when high pressure laboratory equipment is used means that the

• Information File 1 for full experimental data. General notes Warning Carbon monoxide is highly toxic and extremely flammable gas. All reactions were carried out in well ventilated fume cupboards and carbon monoxide detectors were continuously used thought the process. High pressure lab facilities were used

Separation and identification of indene–C₇₀ bisadduct isomers

• Bolong Zhang,
• Jegadesan Subbiah,
• David J. Jones and
• Wallace W. H. Wong

Beilstein J. Org. Chem. 2016, 12, 903–911, doi:10.3762/bjoc.12.88

• device performance. In a previous communication [9], an isomer of IC70BA was obtained by chromatographic separation using both flash chromatography and high pressure liquid chromatography (HPLC). X-ray crystallography revealed that this sample contained the 2 o’clock-B isomer (Figure 2b). This material

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• malonates 6, to obtain 3,4,4-trisubstituted cyclohexanones 7 [17]. It is noted that the organocatalyst employed is the same with the previous example, catalyst 4. Furthermore, this reaction is taking place in the presence of PPY and high pressure was utilized. The authors proposed that PPY deprotonates the

• aminoaldehyde product. Finally, the N-protected aminoaldehyde product can now be cyclized under the reactions’ conditions. Another stereoselective reaction was attempted by Kotsuki’s group presenting an organocatalytic hetero-Diels–Alder reaction between isatin 229 with substituted diene 230. High pressure had

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• CD, the reaction mechanism, environmental concerns, and the reaction scale are only a part of all the information required to design successful preparations. (a) Multihorn-flow US reactor, (b) Cavitational turbine, (c) Pilot-scale BM, (d) High-pressure MW reactor. Trends in CD papers and CD use in

Effective immobilisation of a metathesis catalyst bearing an ammonium-tagged NHC ligand on various solid supports

• Krzysztof Skowerski,
• Jacek Białecki,
• Stefan J. Czarnocki,
• Karolina Żukowska and
• Karol Grela

Beilstein J. Org. Chem. 2016, 12, 5–15, doi:10.3762/bjoc.12.2

• literature that ruthenium residues, present in the reaction mixture after olefin metathesis, can serve as an in situ homogeneous catalyst for high pressure hydrogenation of the newly formed C–C double bonds [57][58][59][60][61]. On this basis, we assumed that the ruthenium complex impregnated on carbon 8-C

• % isolated yield and was found to contain only 5.7 ppm of residual ruthenium after simple filtration (Scheme 4). It should be emphasised that this result was obtained without application of high pressure of hydrogen gas, and did not require any specific equipment. Conclusion In summary, we have reported on

Synthesis of α,β-unsaturated esters via a chemo-enzymatic chain elongation approach by combining carboxylic acid reduction and Wittig reaction

• Yitao Duan,
• Peiyuan Yao,
• Yuncheng Du,
• Jinhui Feng,
• Qiaqing Wu and
• Dunming Zhu

Beilstein J. Org. Chem. 2015, 11, 2245–2251, doi:10.3762/bjoc.11.243

• 4 °C, and disrupted by high pressure homogenizer after re-suspension in binding buffer (20 mM sodium phosphate buffer, 0.5 M NaCl, 20 mM imidazole, pH 7.4). His-CAR or His-PPTase protein in the supernatant fraction was collected from the crude cell lysate by centrifugation at 12 000g for 20 min

Cross metathesis of unsaturated epoxides for the synthesis of polyfunctional building blocks

• Meriem K. Abderrezak,
• Kristýna Šichová,
• Nancy Dominguez-Boblett,
• Antoine Dupé,
• Zahia Kabouche,
• Christian Bruneau and
• Cédric Fischmeister

Beilstein J. Org. Chem. 2015, 11, 1876–1880, doi:10.3762/bjoc.11.201

• -consuming work-up procedures [41]. To the best of our knowledge, such a tandem procedure has not been applied to an epoxide containing olefin. Compound 2 was prepared as described here above (Scheme 1) and the reaction mixture was directly transferred into a high pressure reactor without any work-up

Cross-metathesis of polynorbornene with polyoctenamer: a kinetic study

• Yulia I. Denisova,
• Maria L. Gringolts,
• Alexander S. Peregudov,
• Liya B. Krentsel,
• Ekaterina A. Litmanovich,
• Arkadiy D. Litmanovich,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2015, 11, 1796–1808, doi:10.3762/bjoc.11.195

• argon flow of 70 mL/min in the range from −100 °C to 100 °C. The molar mass of the polymers was determined by GPC on a Waters high pressure chromatograph equipped with a refractometric detector and Microgel mix 1–5 μm 300 × 7.8 mm Waters Styragel HR 5E column, with toluene for PNB and NB-COE copolymers

Grubbs–Hoveyda type catalysts bearing a dicationic N-heterocyclic carbene for biphasic olefin metathesis reactions in ionic liquids

• Maximilian Koy,
• Hagen J. Altmann,
• Benjamin Autenrieth,
• Wolfgang Frey and
• Michael R. Buchmeiser

Beilstein J. Org. Chem. 2015, 11, 1632–1638, doi:10.3762/bjoc.11.178

• ). ICP–OES measurements: The corresponding polymer (20 mg) was added to high-pressure Teflon tubes. Digestion was performed under microwave conditions using aqua regia (10 mL). The mixture was cooled to room temperature, diluted with deionized water (approx. 40 mL), filtered and subjected to ICP–OES for