Functionalization of N-arylglycine esters: electrocatalytic access to C–C bonds mediated by n-Bu₄NI

• Mi-Hai Luo,
• Yang-Ye Jiang,
• Kun Xu,
• Yong-Guo Liu,
• Bao-Guo Sun and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2018, 14, 499–505, doi:10.3762/bjoc.14.35

• given. Scaling up. Control experiments. A plausible mechanism for the electrocatalytic cross dehydrogenative coupling of N-arylglycine esters with C-nucleophiles. Optimization of reaction conditionsa. Supporting Information Supporting Information File 98: General procedure and analytical data

Correction: Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 2128–2130, doi:10.3762/bjoc.13.210

• under ball milling. Substrate scope for the enzymatic resolution of N-benzylated-β3-amino esters. Recycling capacity of immobilized CALB under HSBM conditions. Scaling-up of the enzymatic hydrolysis reaction under ball-milling using substrate rac-1a. Supporting Information Supporting Information File

Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 1728–1734, doi:10.3762/bjoc.13.167

• -benzylated-β3-amino esters. Recycling capacity of immobilized CALB under HSBM conditions. Scaling-up of the enzymatic hydrolysis reaction under ball-milling using substrate rac-1a. Supporting Information Supporting Information File 254: Experimental section, NMR spectra, chromatograms and X-ray diffraction

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

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

• Harri Lonnberg Department of Chemistry, University of Turku, FIN-20014 Turku, Finland 10.3762/bjoc.13.134 Abstract Oligonucleotides are usually prepared in lab scale on a solid support with the aid of a fully automated synthesizer. Scaling up of the equipment has allowed industrial synthesis up

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• while scaling up the production of biomass with the aim of shortening the time and saving resources [120][121]. Although this is a subject for a future detailed study the results of antibacterial activity allowed outlining the positive tendency. Conclusion In summary, the behavior of 5-amino-N-aryl-1H

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

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• 80–90 °C (Figure 1, 3k–p). Varying the secondary amine component with 4-benzylpiperidine, piperidine also worked efficiently to produce the corresponding propargylamine derivatives (3q–t). All products were characterized by FTIR, 1H and 13C NMR spectral data. Scaling up the reaction to gram-scale

Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins

• Laszlo Jicsinszky,
• Marina Caporaso,
• Katia Martina,
• Emanuela Calcio Gaudino and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2016, 12, 2364–2371, doi:10.3762/bjoc.12.230

• increased the yield in the β-CD version. Ten-fold scaling up of the experiments showed increasing yields (entries 4 and 11 in Table 1) but the small scale still prevented to reach the solution reaction outcome but proved our concept. Gram-scale preparations easily overcome the technical difficulties of TU

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

• flow reactor simplifies the practical aspects of the transformation, however, extra precautions were required in order to address and remove any leftover methylamine that would pose a significant hazard during scaling up. The final arylation of 50 was intended to be performed as a SNAr reaction

A new approach for the synthesis of bisindoles through AgOTf as catalyst

• Jorge Beltrá,
• M. Concepción Gimeno and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2014, 10, 2206–2214, doi:10.3762/bjoc.10.228

• without previous distillation. This methodology was also tested with the less active and explored ketone 5k and the reaction rendered a high yield, although 5 mol % of catalyst was required in order to decrease the reaction rate (Table 2, entry 11). Additionally, the possibility of scaling up this process

Synthesis of phosphoramidites of isoGNA, an isomer of glycerol nucleic acid

• Keunsoo Kim,
• Venkateshwarlu Punna,
• Phaneendrasai Karri and
• Ramanarayanan Krishnamurthy

Beilstein J. Org. Chem. 2014, 10, 2131–2138, doi:10.3762/bjoc.10.220

• synthesis of other isoGNA phosphoramidites. For example, the deprotection of 8 to 9 was initially achieved by the treatment with conc. HCl. However, in scaling up the reaction, the loss of the silyl group was found to occur. Therefore, we sought an alternative route and found that the deprotection mediated

Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach

• Tatyana V. Abramova,
• Olga B. Morozova,
• Vladimir N. Silnikov and
• Alexandra V. Yurkovskaya

Beilstein J. Org. Chem. 2013, 9, 2898–2909, doi:10.3762/bjoc.9.326

• strategy for obtaining the model conjugates should provide a synthetic versatility, easy scaling up, and high purity of the title compounds. Although there is a number of well-developed methods of the automatic solid phase supported synthesis (SPSS) of oligonucleotide–peptide conjugates [8], this strategy

• does not ensure the availability of the model conjugates for TR NMR photo-CIDNP experiments due to the lack of versatility and difficulties in scaling up the process. As shown in [9], at least 0.01–0.03 mmol of a compound is required for each photo-CIDNP experiment. In this report, we have designed

• nucleotide block 17. After the deprotection, target conjugates 1–8 were purified by the anion exchange and reversed phase chromatography (RPC) at a medium pressure, which provides the high purity of the final products and easy scaling up in laboratory conditions. The homogeneity and structures of all key

Continuous-flow Heck synthesis of 4-methoxybiphenyl and methyl 4-methoxycinnamate in supercritical carbon dioxide expanded solvent solutions

• Phei Li Lau,
• Ray W. K. Allen and
• Peter Styring

Beilstein J. Org. Chem. 2013, 9, 2886–2897, doi:10.3762/bjoc.9.325

• (THF and methanol) for a further period of 6 hours to remove any products, byproducts and unreacted organic reagent. A larger continuous flow reactor with 3.9 mm internal diameter of length 9 cm was also used as a comparison to assess the effects of scaling up the flow reactor. This was constructed

Investigating the continuous synthesis of a nicotinonitrile precursor to nevirapine

• Ashley R. Longstreet,
• Suzanne M. Opalka,
• Brian S. Campbell,
• B. Frank Gupton and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2013, 9, 2570–2578, doi:10.3762/bjoc.9.292

• , flow chemistry allows chemists to expand their window of process operability by working at elevated temperatures and pressures to increase reaction rates and decrease catalyst loadings [30][31][32][33]. Unlike scaling-up batch reactions, which requires additional optimization, scaling-up flow processes

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

• additional decomposition, the experiment was repeated over a shorter reaction time at a slightly lower temperature (Table 1, entry 9) but this caused no improvement in outcome (28% yield). Difficulties in scaling up a microwave-assisted batch reaction had been noted previously for the Bohlmann–Rahtz

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

• direct their radiation towards a sample at the centre. There is usually a fan located at the bottom of the cabinet to ensure sufficient cooling. These are useful for scaling up batch reactions that use low-pressure lamps. • Falling-film reactors. A falling-film reactor is particularly useful for scaling

• know-how, e.g., which lamp, glassware and solvent to use. • Safety. Medium pressure mercury lamps operate optimally at ~600 °C and emit intense and potentially damaging UV radiation. • Difficulty in scaling up. The Toray caprolactam process proves this is not a problem at the industrial scale. However

• software control. Nearly all common batch reactions [16] can now be carried out in flow. One of the key issues of scaling-up organic photochemistry in an immersion-well (batch) reactor is that light penetration to the surrounding solution is limited by the high absorption of the substrate and falls off

A general and facile one-pot process of isothiocyanates from amines under aqueous conditions

• Nan Sun,
• Bin Li,
• Jianping Shao,
• Weimin Mo,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2012, 8, 61–70, doi:10.3762/bjoc.8.6

• . Moreover, to evaluate the procedure for the potential scaling-up capability, we used aniline as test substrate to scale up the synthesis in 1.0 mol scale. It became clear that the desired phenyl isothiocyanate could be conveniently isolated via vacuum distillation (Table 2, entry 9). This experiment

Scaling up of continuous-flow, microwave-assisted, organic reactions by varying the size of Pd-functionalized catalytic monoliths

• Ping He,
• Stephen J. Haswell,
• Paul D. I. Fletcher,
• Stephen M. Kelly and
• Andrew Mansfield

Beilstein J. Org. Chem. 2011, 7, 1150–1157, doi:10.3762/bjoc.7.133

• , respectively. Under optimal reaction conditions the quantity of product could be increased from 31 mg per hour to 340 mg per hour simply by changing the volumetric capacity of the monolith. Keywords: continuous flow; microwave heating; monolith; scaling-up; Suzuki–Miyaura reaction; Introduction Interest in

• alternative approach can be envisaged, i.e., changing the monolith length for scaling up whilst maintaining the required intrinsic properties. It is worth considering the relative advantages and disadvantages of these two possible approaches in light of the work presented. Increasing the diameter of a fixed

Continuous flow photolysis of aryl azides: Preparation of 3H-azepinones

• Farhan R. Bou-Hamdan,
• François Lévesque,
• Alexander G. O'Brien and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2011, 7, 1124–1129, doi:10.3762/bjoc.7.129

• reactions [8][9][10][11][12][13]. As, from the Beer–Lambert law, the intensity of light decreases exponentially with increasing distance from the light source, minimization of the path length in a continuous flow photoreactor ensures efficient and uniform irradiation of the sample [14], and scaling up is

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

• further study and even commercialisation it is then required to be produced on a larger scale. The problem is that to move from small discovery to larger pilot or commercial scale production is not simply a case of scaling up the quantities of reagents and solvents [4]. There are also supply issues when

• containment in the case of a failure [2][3]. Scaling up in volume of a reactor has implications on the mass and heat transfer within the system so the reaction must be re-optimised for the prevailing conditions. This is a time-consuming process and often results in the abandoning of the bench scale process in