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

• applications, first and foremost in the fragrance and flavor industries, but also in the pharmaceutical and chemical industries [1][2][3]. Myrcene is a naturally occurring, acyclic monoterpene which is used industrially for the manufacture of flavoring substances and fragrances; in research it is used as a

• percentages (<5%) in hops [3], celery [3], dill [9], rosemary [3], tarragon [10] and nutmeg [3] to name but a few. A review by Behr and Johnen [3] describes the manufacture of myrcene from other terpenes, as well as several synthetic routes based on this versatile and reactive starting material to form

• particular, the reaction of myrcene (1) with acrylic acid (2b) was investigated in detail, through batch and continuous-flow methods. The intensified flow process presents a more compact and efficient alternative to classic batch manufacture for the production of Diels–Alder adduct surfactants from myrcene

3D printed fluidics with embedded analytic functionality for automated reaction optimisation

• Andrew J. Capel,
• Andrew Wright,
• Matthew J. Harding,
• George W. Weaver,
• Yuqi Li,
• Russell A. Harris,
• Steve Edmondson,
• Ruth D. Goodridge and
• Steven D. R. Christie

Beilstein J. Org. Chem. 2017, 13, 111–119, doi:10.3762/bjoc.13.14

• -dimensional parts, often with geometries which would be extremely complex, or in some cases impossible to manufacture using more conventional subtractive manufacturing processes [1]. In AM, parts are built layer-by-layer, using processes such as material extrusion [2], material jetting [3], vat

• -power energy source, typically a laser, to selectively melt a powder bed into a single solid body [17]. SLM can manufacture parts in a range of chemically inert and thermally stable metals such as stainless steel [18], aluminium and titanium [19][20], and is therefore an attractive technique for a

• part to be held within by a commercially available sprung clip. The flow cell itself had a path length of 6 mm. One of the unique features of using AM to manufacture this type of part is that manufacturing costs are directly proportional to the volume of material used and not the complexity of the

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

• . This review highlights these transformations and discusses how this previous research can be applied to the future of organic compound manufacture. Keywords: continuous; extrusion; industry; organic; synthesis; Review Extrusion methodology Extrusion is an umbrella term covering a family of processes

• (<30 publications, mainly from researchers at Amgen) and studies on the extrusion process itself with regards to cocrystal manufacture is also gaining momentum. There are a few publications investigating the effect of screw speed and temperature on the process [37]. There is also an example in the

• and usage of MOFs increases, the manufacture of these materials, which typically require solvothermal techniques, has become a key research area. Mechanochemical synthesis of several MOFs has been reported typically by ball milling [48], and James et al. have scaled up the synthesis of HKUST-1, ZIF-8

Isosorbide and dimethyl carbonate: a green match

• Fabio Aricò and
• Pietro Tundo

Beilstein J. Org. Chem. 2016, 12, 2256–2266, doi:10.3762/bjoc.12.218

• :3,6-dianhydro-D-glucitol, is a sugar alcohol, found in nature as the sweet constituent of many berries and fruits from which it was isolated for the first time in 1872. Its large scale manufacture began in the 1950s, due to the growing applications as humectant in cosmetology and sugar substitute in

Diels–Alder reactions in confined spaces: the influence of catalyst structure and the nature of active sites for the retro-Diels–Alder reaction

• Ángel Cantín,
• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2016, 12, 2181–2188, doi:10.3762/bjoc.12.208

• terephthalate that is used for the large-scale manufacture of plastic bottles among others. The authors do not find transport limitations within the zeolite framework to the rate of the reaction [27]. Interestingly, when Brønsted acid containing zeolites (Al-β) are used as catalyst, there is a decrease in the

Solvent-free synthesis of novel para-menthane-3,8-diol ester derivatives from citronellal using a polymer-supported scandium triflate catalyst

• Lubabalo Mafu,
• Ben Zeelie and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 2046–2054, doi:10.3762/bjoc.12.193

• : acylation; diesters; para-menthane-3,8-diol; PS-Sc(OTf)3; Introduction Although South Africa has a substantial petrochemical industry, the fine chemical industry is very small and most chemicals are imported. As such there is significant interest in the use of natural resources for the manufacture of added

The in situ generation and reactive quench of diazonium compounds in the synthesis of azo compounds in microreactors

• Faith M. Akwi and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 1987–2004, doi:10.3762/bjoc.12.186

• conjunction with the existing techniques. Microreactor technology is one such technology that can be used in the manufacture of these dyes. If used in conjunction with existing azo dye degradation techniques the amount of waste generated can easily be managed. Hisamoto et al., for example, used ‘phase

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

• impacted the art of organic synthesis and manufacture [1][2][3][4][5][6][7]. The efficiency of chemical reactions can be greatly enhanced over common batch processes and new approaches to the optimization of established reaction protocols and the execution of hitherto unfeasible processes can be enabled

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• hydroperoxides, aryl hydroperoxides, ketone peroxides, dialkyl peroxides, diacyl peroxides, peroxy esters, peroxydicarbonates, peroxyacetals, and inorganic peroxides are the most important radical initiators that are widely used in industrial processes in the manufacture of polymers from unsaturated monomers [1

• rearrangements and related processes play an important role in the chemistry of oxidation processes. Thus, the key reagent in the Sharpless epoxidation of allylic alcohols [48] and in the manufacture of propylene oxide via the Prilezhaev reaction [49][50][51] is tert-butyl hydroperoxide. In industry, phenol and

A convergent, umpoled synthesis of 2-(1-amidoalkyl)pyridines

• Tarn C. Johnson and
• Stephen P. Marsden

Beilstein J. Org. Chem. 2016, 12, 1–4, doi:10.3762/bjoc.12.1

• structurally novel and diverse substituted pyridines for new medicines discovery, and for the development of clean, efficient and robust methods for their manufacture on large scale. Pyridines bearing a 1-amidoalkyl substituent at the 2-position are found in numerous biologically active natural products such

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

• hypochlorite (NaOCl) is an inexpensive byproduct of chlorine manufacture, and offers a safer, greener source of electrophilic chlorine for producing N-chloramines [11][14][22]. Reaction times can, however, be long [14][23][24], and yields low [25]. Zhong et al. have reported a process using NaOCl to generate t

Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions

• Paul P. Kelly,
• Anja Eichler,
• Susanne Herter,
• David C. Kranz,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2015, 11, 1713–1720, doi:10.3762/bjoc.11.186

• acknowledge support from the Centre of Excellence for Biocatalysis, Biotransformations and Biocatalytic Manufacture (CoEBio3, to PPK), the FP7-PEOPLE-2011-ITN under grant agreement no. 289217 (P4fifty, to AE), the Innovative Medicines Initiative Joint Undertaking under the grant agreement no. 115360 (Chemical

The enantioselective synthesis of (S)-(+)-mianserin and (S)-(+)-epinastine

• Piotr Roszkowski,
• Jan. K. Maurin and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2015, 11, 1509–1513, doi:10.3762/bjoc.11.164

• auxiliary was described by the Czarnocki group [7]. For the commercial manufacture of mianserin enantiomers both the above mentioned processes are rather unjustified economically and the most advantageous method could be the enantioselective synthesis. Considering our experience in asymmetric synthesis of

Surprisingly facile CO₂ insertion into cobalt alkoxide bonds: A theoretical investigation

• Willem K. Offermans,
• Claudia Bizzarri,
• Walter Leitner and
• Thomas E. Müller

Beilstein J. Org. Chem. 2015, 11, 1340–1351, doi:10.3762/bjoc.11.144

• carbonates. In consequence, industrially relevant catalysts, combined with efficient processes, have only recently emerged for the manufacture of alternating polycarbonates [10] and polyethercarbonates [11]. The respective research has mainly focussed on homogeneous zinc–alkoxide complexes [12] and chromium

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

• synthetic capabilities. As a result many new preparative routes have been designed towards commercially relevant drug compounds achieving more efficient and reproducible manufacture. This review article aims to illustrate the holistic systems approach and diverse applications of flow chemistry to the

• : 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

• order to surmount these obstacles and for us to achieve the vision of true continuous manufacture of pharmaceuticals. Review Early flow processing approaches The first published examples of flow chemistry applied to the synthesis of pharmaceutically active molecules emerged in the early 2000s when

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

Triphenylene discotic liquid crystal trimers synthesized by Co₂(CO)₈-catalyzed terminal alkyne [2 + 2 + 2] cycloaddition

• Bin Han,
• Ping Hu,
• Bi-Qin Wang,
• Carl Redshaw and
• Ke-Qing Zhao

Beilstein J. Org. Chem. 2013, 9, 2852–2861, doi:10.3762/bjoc.9.321

• , ink-jet printing and roll-to-roll processing, so that these cost-effective deposition methods can be used to manufacture electronic devices. Therefore, the exploration of efficient synthetic methods for the DLC oligomers and studying the properties of them are fundamental. The construction methods of

Microflow photochemistry: UVC-induced [2 + 2]-photoadditions to furanone in a microcapillary reactor

• Sylvestre Bachollet,
• Kimitada Terao,
• Shin Aida,
• Yasuhiro Nishiyama,
• Kiyomi Kakiuchi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2013, 9, 2015–2021, doi:10.3762/bjoc.9.237

• manufacture, restricted in length and fragile in handling. We have instead applied inexpensive and flexible FEP tubing that was wrapped tightly around a Pyrex glass base and placed this simple unit inside a common Rayonet chamber reactor (‘outside-in’ irradiation). A different immersion well type FEP

Enhancement of efficiency in organic photovoltaic devices containing self-complementary hydrogen-bonding domains

• Rohan J. Kumar,
• Jegadesan Subbiah and
• Andrew B. Holmes

Beilstein J. Org. Chem. 2013, 9, 1102–1110, doi:10.3762/bjoc.9.122

• -processing, leading to cost and energy input advantages in device manufacture. Recently, a donor–acceptor small molecule with a cyanopyridone moiety as the acceptor motif and displaying moderate photovoltaic efficiency in a BHJ device with a fullerene was reported [20]. The efficiency of these optimized

• a variety of solvents and the domain size controlled through the judicious choice of solvent. This will be advantageous for use in high-throughput production methods, ultimately lowering the cost and energy for the manufacture of organic photovoltaic devices. Conclusion A self-complementary hydrogen

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

• ], Corey's synthesis of carophyllene alcohol [5][6] and Wender's synthesis of cedrene [7] are just three outstanding examples to highlight. Photochemistry has also made the transition to industrial-scale synthesis. For example the Toray process [8][9][10] for the synthesis of caprolactam, used to manufacture

• manufacture of a ten-capillary device fabricated from FEP tubing (1.6 mm o.d., 0.8 mm i.d.), each tube having an internal volume of 5 mL. The tubing was wrapped around two 18 W UVA (365 nm) lamps, five tubes per lamp, giving a device that clearly fits into the macroflow regime as defined in this review. By

Synthesis of compounds related to the anti-migraine drug eletriptan hydrobromide

• Suri Babu Madasu,
• Nagaji Ambabhai Vekariya,
• M. N. V. D. Hari Kiran,
• Badarinadh Gupta,
• Aminul Islam,
• Paul S. Douglas and
• Korupolu Raghu Babu

Beilstein J. Org. Chem. 2012, 8, 1400–1405, doi:10.3762/bjoc.8.162

• Chemistry Department, AU College of Engineering, Andhra University, Visakhapatnam-530003, Andhra Pradesh, India 10.3762/bjoc.8.162 Abstract Eletriptan hydrobromide (1) is a selective serotonin (5-HT1) agonist, used for the acute treatment of the headache phase of migraine attacks. During the manufacture of

• of eletriptan hydrobromide is 97 mg per day, which is equivalent to 80 mg of eletriptan base [10]. During the manufacture of eletriptan hydrobromide (1), many process-related impurities have been identified. As per ICH guide lines the acceptable level for known and unknown related impurities in the

Chimeric self-sufficient P450cam-RhFRed biocatalysts with broad substrate scope

• Aélig Robin,
• Valentin Köhler,
• Alison Jones,
• Afruja Ali,
• Paul P. Kelly,
• Elaine O'Reilly,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2011, 7, 1494–1498, doi:10.3762/bjoc.7.173

• Manufacture (CoEBio3) and the Royal Society (Wolfson Merit Award to SLF) for financial support.

Efficient and selective chemical transformations under flow conditions: The combination of supported catalysts and supercritical fluids

• M. Isabel Burguete,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2011, 7, 1347–1359, doi:10.3762/bjoc.7.159

• ][84]. As a result, the chemical industry is currently exploring the great potential of biocatalysis to manufacture both bulk and fine chemicals [85][86]. Although many of the reported examples involve the use of batch conditions, different examples of continuous biocatalytic processes have been

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• reaction conditions and gave rise to numerous by-products. An improved route was developed for the compounds large scale manufacture. The refined process route (Scheme 56) starts with a sequential bis-acylation of hydrazine with ethyl trifluoroacetate and chloroacetyl chloride [85]. The resulting hydrazide

Aromatic and heterocyclic perfluoroalkyl sulfides. Methods of preparation

• Vladimir N. Boiko

Beilstein J. Org. Chem. 2010, 6, 880–921, doi:10.3762/bjoc.6.88