Extrusion – back to the future: Using an established technique to reform automated chemical synthesis

• Deborah E. Crawford

Beilstein J. Org. Chem. 2017, 13, 65–75, doi:10.3762/bjoc.13.9

• . 3–10 kg h−1 (after both transformations have been carried out) [16]. Unfortunately, there is no example in the literature for this reaction carried out in batch, however, Meyer reports on the general scalability of batch polymerisation and comments that up to 200 kg d−1 quantities can be obtained

A direct method for the N-tetraalkylation of azamacrocycles

• Andrew J. Counsell,
• Angus T. Jones,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2016, 12, 2457–2461, doi:10.3762/bjoc.12.239

• conditions (immiscible chloroform/sodium hydroxide solvent system [36][37]) gave a further increase in yield (to 60%), but the reaction under these conditions required long run times (up to several days) and afforded poor scalability, with the yield dropping to 42% when the reaction was carried out on a 2.5

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

• of NEt3 and 1 equiv of pyridine at 40 °C for 48 h confirming their low reactivity. Reaction scaling Finally, the robustness of the process and potential for scalability of the general reaction conditions was demonstrated by the synthesis of 19 at a 10 mmol scale, a factor of fourteen times the

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

• -dehalogenation pathway becomes preferred, giving 1,3-dimethoxybenzene as the main product, which was isolated in 31% yield in the case of 29 and 3-chlorotoluene in the case of 30 which was isolated in 52% yield (Scheme 4). To demonstrate the potential scalability of the reaction conditions, the synthesis of

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• ) [45]. Unfortunately, this route was found to be less effective in terms of isolated yields and scalability. Thus, the iron-catalyzed procedure was applied and multigram quantities of 12 were readily obtained. As shown in Scheme 3, we next focused on the further derivatization of amine 12 towards

Iridium/N-heterocyclic carbene-catalyzed C–H borylation of arenes by diisopropylaminoborane

• Mamoru Tobisu,
• Takuya Igarashi and
• Naoto Chatani

Beilstein J. Org. Chem. 2016, 12, 654–661, doi:10.3762/bjoc.12.65

• chromatography over silica gel eluting with hexane/EtOAc. Product-containing fractions were concentrated in vacuo to give a pure borylated product. Catalytic C–H borylation of arenes and related reported boron sources. Scalability and derivatization. Effect of the ligand on the Ir-catalyzed borylation of 2 with

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

• highlight the huge advantages and potential scalability of these so-called enabling technologies that maximize heat and mass transfer. Although many advances have been made during the past decade, the most exciting results in this field are surely yet to come. Ultrasound US irradiation is an environmentally

• miniaturized continuous flow reactor, also called microreactor, offers many advantages over conventional scale reactors, including considerable improved energy exploitation, increased reaction speed and yield, safety, reliability, scalability, on-site/on-demand production, etc., and a much finer degree of

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

• : continuous processing; flow synthesis; in-line analysis; manufacture; pharmaceuticals; scalability; Introduction The last 20 years have witnessed a true renaissance in the way synthetic chemistry is performed due to the implementation of various enabling technologies allowing the modern synthesis chemist to

Radical-mediated dehydrative preparation of cyclic imides using (NH₄)₂S₂O₈–DMSO: application to the synthesis of vernakalant

• Dnyaneshwar N. Garad,
• Subhash D. Tanpure and
• Santosh B. Mhaske

Beilstein J. Org. Chem. 2015, 11, 1008–1016, doi:10.3762/bjoc.11.113

• byproducts, difficult to access starting materials, azeotropoic removal of water, column purification, harsh reaction conditions, longer reaction time and lack of scalability are some of the drawbacks of prior methods. The development of improved processes to such an important building block is an area of

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• ][55][56][57][58][59][60][61]. Due to the nature of the reaction and ready availability of catalyst, these asymmetric reactions could be undertaken at the mole-scale (giving more than 100 g of product), with possibility of both catalyst recovery and reuse. The scalability of these reactions is first

Photovoltaic-driven organic electrosynthesis and efforts toward more sustainable oxidation reactions

• Bichlien H. Nguyen,
• Robert J. Perkins,
• Jake A. Smith and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2015, 11, 280–287, doi:10.3762/bjoc.11.32

• discussion here because the reaction serves to both illustrate the range of oxidation reactions that can be performed in a catalytic fashion using a simple photovoltaic and highlight the scalability of the process. In order to perform the reaction on a preparative scale, the array-based method was increased

An improved procedure for the preparation of Ru(bpz)₃(PF₆)₂ via a high-yielding synthesis of 2,2’-bipyrazine

• Danielle M. Schultz,
• James W. Sawicki and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2015, 11, 61–65, doi:10.3762/bjoc.11.9

• explored the scalability of the optimized conditions, and found that they remained applicable on multi-gram scale (Scheme 2). Thus, exposure of 4 g of 2-iodopyrazine to the optimized conditions from Table 1 cleanly produced 1.25 g of 2,2’-bipyrazine in 81% isolated yield. A portion of this material was

Continuous flow nitration in miniaturized devices

• Amol A. Kulkarni

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

• acid and later with benzene. Orifices with different diameters induce different flow regimes in the reactor. The authors claim this microreactor has infinite scalability, as it is based on the addition of different components in sequence. In one of the first reports on the continuous flow nitration of

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• pharmacological activities of compounds based on the 3-piperidinol scaffold, a step-economic, scalable and stereodivergent synthesis of both cis- and trans-diastereomers of B in good diastereoselectivities is highly desirable. In the syntheses of potentially new drug candidates scalability is a significant factor

• 44%, demonstrating the scalability and high practicability of our sequence. The relative configurations of compounds 9 and 11 were proven by NOE spectroscopy of piperidinols cis-11a–d, trans-11a, cis- and trans-16c, L-733,060.HCl and of oxazolidinones trans-10a and trans-10c (see Supporting

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

• scalability under microwave irradiation [10] and under continuous flow processing, observed by ourselves and others [73][74], this technology stands out as the heating method of choice for the preparation of 1,4-DHP derivatives. Conclusion These studies have demonstrated that a microwave flow reactor can be

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

• , the scalability of these reactions is limited by the required low concentration (~10−3 mol·L−1) and usually long reaction times (>20 h). Therefore, most of the applications of this method are limited to small scale (<0.5 mmol), making it unsuitable for gram-scale synthesis of helicene-like molecules

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

• emerged [59]. The main driving forces behind these CF methodologies are the safety aspects associated with the handling of azides and the inherent scalability of flow processing. Moreover, when organic azides are formed in situ, operational safety can be further improved [55][57]. We envisioned that it

• , the scalability of CF procedures is a straightforward function of time and the flow rate, and the risks associated with the accumulation of hazardous species are minimized, because the solution of the reactants is eluting continuously from the active zone of the reactor [33][34][44][45][60]. The CF

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

Discovery of practical production processes for arylsulfur pentafluorides and their higher homologues, bis- and tris(sulfur pentafluorides): Beginning of a new era of “super-trifluoromethyl” arene chemistry and its industry

• Teruo Umemoto,
• Lloyd M. Garrick and
• Norimichi Saito

Beilstein J. Org. Chem. 2012, 8, 461–471, doi:10.3762/bjoc.8.53

• to the previous methods using AgF2, F2, or XeF2, or multiple-step methods starting from SF5Br or SF5Cl, in terms of cost, applicability, and scalability of production, the processes developed here can be used as the first practical and economical methods for the production of many kinds of arylsulfur

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

• maintaining the intrinsic benefits of the reaction geometry offered when using microreactor methodology. In this work we report a simple and effective approach for achieving volumetric scalability in a flow reaction system through the use of Pd-supported silica-based monolithic reactors coupled with microwave