A concise flow synthesis of indole-3-carboxylic ester and its derivatisation to an auxin mimic

• Marcus Baumann,
• Ian R. Baxendale and
• Fabien Deplante

Beilstein J. Org. Chem. 2017, 13, 2549–2560, doi:10.3762/bjoc.13.251

• the optimum additive (Table 2, entries 11–14). Stronger acids or higher loading of acid often resulted in the generation of high internal pressures and in certain cases the formation of precipitates was noted requiring premature termination of the run and a safe shutdown. Using acetic acid and

Exploring mechanochemistry to turn organic bio-relevant molecules into metal-organic frameworks: a short review

• Vânia André,
• Sílvia Quaresma,
• João Luís Ferreira da Silva and
• M. Teresa Duarte

Beilstein J. Org. Chem. 2017, 13, 2416–2427, doi:10.3762/bjoc.13.239

• be studied for their potential medicinal applications. Here, the main focus was their use as drug-delivery systems [71][72][89], with particular attention to the toxicity of the metal centers [84]. Toxicity is a concern not only for the safe use of these compounds for humans but also for

• (encapsulated) as a guest within the pores of the MOF. In the second situation, the choice of the linker is crucial, as it needs to be an organic molecule listed of the generally regarded as safe (GRAS) compounds, an endogenous compound or a bioactive molecule. In both classes, the judicious choice of the

• liquid led to the formation of a 1D coordination polymer monohydrate, a tetrahydrate complex and an octahydrate, respectively (Figure 2) [7][29]. BioMOFs based on generally regarded as safe (GRAS), bioactive or endogenous linkers for the encapsulation of APIs Another approach to build a BioMOF consists

Synthesis and application of trifluoroethoxy-substituted phthalocyanines and subphthalocyanines

• Satoru Mori and
• Norio Shibata

Beilstein J. Org. Chem. 2017, 13, 2273–2296, doi:10.3762/bjoc.13.224

• embryos. These results suggest that the cyclodextrin conjugate does not display cytotoxicity when not irradiated with light. Therefore, the cyclodextrin conjugate has the potential to be effective and very safe. Application of trifluoroethoxy-substituted phthalocyanines to functional materials Development

Solid-state studies and antioxidant properties of the γ-cyclodextrin·fisetin inclusion compound

• Joana M. Pais,
• Maria João Barroca,
• Maria Paula M. Marques,
• Filipe A. Almeida Paz and
• Susana S. Braga

Beilstein J. Org. Chem. 2017, 13, 2138–2145, doi:10.3762/bjoc.13.212

• GRAS status (list of food additives that are ‘generally recognized as safe’) [9]. The present work describes the preparation of a water-soluble, solid inclusion compound of fisetin with γ-CD (see Scheme 1 for structure and atom labeling). The formation of the γ-CD·fisetin inclusion compound as a solid

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• Warner have proposed 12 Principles of Green Chemistry as a guide to help making chemical processes more environmentally friendly [13][14]. Many of the requirements contained in these principles (e.g., prevention, atom economy, energy efficiency, catalysis, safe synthesis) can be met if the reactions are

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• other chronic and acute neurogenerative diseases [99]. This molecule reached the clinical development phase, consequently a safe, robust and economic scale-up process was investigated by the researcher as the original process was incompatible towards scale-up. The investigation indeed provided a better

Mechanochemical borylation of aryldiazonium salts; merging light and ball milling

• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1463–1469, doi:10.3762/bjoc.13.144

• the diazonium salt 1a and B2pin2 (2) was milled for 2 h at 25 Hz in a mixer mill, using a Teflon milling jar and ZrO2 ball bearings. The safe use of diazonium salt under ball milling conditions has been previously reported in the literature [19]. The analysis of the reaction mixture by 1H NMR

Detection of therapeutic radiation in three-dimensions

• John A. Adamovics

Beilstein J. Org. Chem. 2017, 13, 1325–1331, doi:10.3762/bjoc.13.129

• (dosimeters) with sufficient capability to verify complex treatments and ensure accurate, safe implementation [2]. There have been reports of high failure rates for complex radiation treatments [3][4]. These concerns and others have led many to recognize an urgent need to strengthen the foundations of quality

α-Acetoxyarone synthesis via iodine-catalyzed and tert-butyl hydroperoxide-mediateded self-intermolecular oxidative coupling of aryl ketones

• Liquan Tan,
• Cui Chen and
• Weibing Liu

Beilstein J. Org. Chem. 2017, 13, 1079–1084, doi:10.3762/bjoc.13.107

• an attractive target for organic chemists. Simple, inexpensive, and metal-free methods [14][15], involving safe and clean oxidation procedures, need to be developed. Here, we report a metal-free, novel, and efficient self-intermolecular oxidative coupling procedure for the synthesis of α-acetoxyaryl

Use of costic acid, a natural extract from Dittrichia viscosa, for the control of Varroa destructor, a parasite of the European honey bee

• Kalliopi Sofou,
• Demosthenis Isaakidis,
• Apostolos Spyros,
• Anita Büttner,
• Athanassios Giannis and
• Haralambos E. Katerinopoulos

Beilstein J. Org. Chem. 2017, 13, 952–959, doi:10.3762/bjoc.13.96

• . Costic acid exhibited potent in vivo acaricidal activity against the parasite. Initial experiments showed that the compound is not toxic for human umbilical vein endothelial cells (HUVEC) at concentrations of up to 230 micromolar (μM), indicating that costic acid could be used as a safe, low-cost and

• amount of oxalic acid in honey [23][24][25] and has no toxic effects on bees. However, later studies indicated that the utilization of oxalic acid by either trickling or spraying has a detrimental effect on brood development when open brood is present, and is therefore not as safe as it has been assessed

• treatment does not have a toxic effect on the host. The fact that the compound is also not toxic against human umbilical vein endothelial cells (HUVEC) indicates that it could be used as a safe, environment friendly, and low-cost efficient agent of controlling varroosis in Apis mellifera colonies

Total synthesis of TMG-chitotriomycin based on an automated electrochemical assembly of a disaccharide building block

• Yuta Isoda,
• Norihiko Sasaki,
• Kei Kitamura,
• Shuji Takahashi,
• Sujit Manmode,
• Naoko Takeda-Okuda,
• Jun-ichi Tamura,
• Toshiki Nokami and
• Toshiyuki Itoh

Beilstein J. Org. Chem. 2017, 13, 919–924, doi:10.3762/bjoc.13.93

• synthesis was completed by Yu [8][9]. Although the activity of TMG-chitotriomycin (1) was moderate, it selectively inhibits glucosaminidases derived from insects and fungi. Therefore, TMG-chitotriomycin (1) has a potential as a lead compound for safe insecticides and pesticides. Recently, the total

Isoxazole derivatives as new nitric oxide elicitors in plants

• Anca Oancea,
• Emilian Georgescu,
• Florentina Georgescu,
• Alina Nicolescu,
• Elena Iulia Oprita,
• Catalina Tudora,
• Lucian Vladulescu,
• Marius-Constantin Vladulescu,
• Florin Oancea and
• Calin Deleanu

Beilstein J. Org. Chem. 2017, 13, 659–664, doi:10.3762/bjoc.13.65

• Ministry of National Education – Research Activity, UEFISCDI, Project PN-II-PT-PCCA-2013-4-0267 – SAFE-SEL, contract 186/2014. Access to research infrastructure developed in the “Petru Poni” Institute of Macromolecular Chemistry through the European Social Fund for Regional Development, Competitiveness

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

• implications in economy and politics. Recent studies predicted a growth of green chemical processing up to $100 billion in 2020 (Pike Research study) [1]. All this offers important and arduous challenges expressed in terms of new synthetic strategies using sustainable, safe, and less toxic materials. On green

• the employment of readily available and cheap starting materials, the safe handling of highly thermally unstable or dangerous intermediates, and the use of higher temperature with respect to the batch mode in which the proposed reactions have to be carried out at −78 °C. The use of 2-MeTHF as greener

Poly(ethylene glycol)s as grinding additives in the mechanochemical preparation of highly functionalized 3,5-disubstituted hydantoins

• Andrea Mascitti,
• Massimiliano Lupacchini,
• Ruben Guerra,
• Ilya Taydakov,
• Lucia Tonucci,
• Nicola d’Alessandro,
• Frederic Lamaty,
• Jean Martinez and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 19–25, doi:10.3762/bjoc.13.3

• investigated in the presence of various poly(ethylene) glycols (PEGs), as safe grinding assisting agents (liquid-assisted grinding, LAG). A comparative study under dry-grinding conditions was also performed. The results showed that the cyclization reaction was influenced by the amount of the PEG grinding

• ) glycols (PEGs) are eco-friendly solvents [1][2], finding applications in the biomedical field and for pharmaceutical formulations [3] and catalysis [4]. PEG-based reaction media [1] are safe reaction environments, efficiently heated by microwaves [5], but their use in organic transformations activated by

• physical aspects also connected to the intrinsic properties of the polymer. In addition, PEG polymers were demonstrated as a valid eco-friendly and safe alternative to classic solvents used in liquid-assisted-grinding procedures (LAG) [18][19][20][21][22] due to their low melting point (45–60 °C), enabling

Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2017, 13, 10–18, doi:10.3762/bjoc.13.2

• free cholesterol accumulation in various organs and prolongs the lifespan of Npc1−/− mice and NPC-diseased human fibroblasts [9][10][19]. Toxicological studies indicate that HP-β-CD is generally safe. However, a recent study has found that repeated administration of high doses of HP-β-CD causes hearing

Characterization of the synthetic cannabinoid MDMB-CHMCZCA

• Carina Weber,
• Stefan Pusch,
• Dieter Schollmeyer,
• Sascha Münster-Müller,
• Michael Pütz and
• Till Opatz

Beilstein J. Org. Chem. 2016, 12, 2808–2815, doi:10.3762/bjoc.12.279

• functional theory, see Supporting Information File 1 for details), a comparison of the experimental and calculated ECD spectra did not allow for a safe assignment of the cannabimimetic’s absolute configuration (Figure 4). The main two positive ECD signals in the range above 230 nm are correctly predicted by

From betaines to anionic N-heterocyclic carbenes. Borane, gold, rhodium, and nickel complexes starting from an imidazoliumphenolate and its carbene tautomer

• Ming Liu,
• Jan C. Namyslo,
• Martin Nieger,
• Mika Polamo and
• Andreas Schmidt

Beilstein J. Org. Chem. 2016, 12, 2673–2681, doi:10.3762/bjoc.12.264

• biological activities of NHC complexes [23][24]. In the last decade, attention has also been directed to anionic N-heterocyclic carbenes [25]. In this context, mesomeric betaines are interesting from two viewpoints. They are not only able to undergo tautomerisations to neutral NHCs and thus provide a safe

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• are considered safe for parenteral administration. In a general way, the γ-CD, HP-β-CD and SBE-β-CD, S-β-CD and G2-β-CD appear to be globally safer than α-, β- and alkylated CDs which are less suitable for parental administration [44][45]. Table 3 presents the pharmacokinetics and safety overview of

• reported side effect such as minor gastrointestinal symptoms (3% for the placebo). Consequently, the use of α-CD, safe and well tolerated, showed a reduction in LDL cholesterol, and an improvement of fasting plasma glucose. The ability of CDs to change the contractibility of arterial smooth muscles

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

• external cooling of the reaction. To facilitate safe scale-up of this reaction we initially investigated a direct transfer of the batch process (Scheme 3) to continuous mode. Although initial investigations involving small throughput had shown promise, the practicalities of employing dichloromethane at

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

• can be performed on large scales under safe conditions. However, there can be some difficulties (compounds 3 and 4, entries 2–4, 7–11 in Table 1) in reaction and during purification, meaning that we therefore also decided to test per-6-chloro-β-CD from which the more ionic TU salt can be formed and

Tunable microwave-assisted method for the solvent-free and catalyst-free peracetylation of natural products

• Manuela Oliverio,
• Paola Costanzo,
• Monica Nardi,
• Carla Calandruccio,
• Raffaele Salerno and
• Antonio Procopio

Beilstein J. Org. Chem. 2016, 12, 2222–2233, doi:10.3762/bjoc.12.214

• of hydrophilic products and to obtain safe and stable pro-drugs. Results: A totally green, solvent-free and catalyst-free microwave (MW)-assisted method for peracetylation of natural products such as oleuropein, alpha-hederin, quercetin and rutin is presented. By simply tuning the MW heating program

• preferably acetic anhydride in solvent free conditions, in presence of non-toxic homogeneous catalysts such as environmental safe Lewis acids [13][14]. Moreover, the need to easily recover and reuse the catalyst, thus reducing the work-up procedure to a simple filtration, resulted in the growing use of

• and safe as it employs food grade acetic anhydride as acetylating agent, solvent-free and catalyst-free conditions, an easy work-up procedure affording the peracetylated molecules without any chromatographic purification. The possibility to contemporary acetylate several chemically diverse –OH groups

Economical and scalable synthesis of 6-amino-2-cyanobenzothiazole

• Jacob R. Hauser,
• Hester A. Beard,
• Mary E. Bayana,
• Katherine E. Jolley,
• Stuart L. Warriner and
• Robin S. Bon

Beilstein J. Org. Chem. 2016, 12, 2019–2025, doi:10.3762/bjoc.12.189

• acetonitrile solution outweighs this exotherm under the experimental conditions. Our results suggest that a slow addition of a dilute aqueous NaCN solution is a safe method for scale-up of the cyanation reaction, provided the concentration of the solution allows an overall reaction endotherm to be maintained

• bioorthogonal ligation and bioluminescent imaging. The procedure allowed the safe synthesis of 8 at multigram scale and in high purity. In addition, the sole use of filtrations and crystallisations for purification of all intermediates and products, in combination with the endothermic nature of the controlled

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

• selective oxidations of various organic molecules (Scheme 5). From a conceptual point of view, the combination of two of the most abundant “reagents” on the surface of our planet, oxygen and visible light, with a safe, scalable, and efficient reactor technology for chemical reactions constitutes an approach

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

• 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

On the cause of low thermal stability of ethyl halodiazoacetates

• Magnus Mortén,
• Martin Hennum and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2016, 12, 1590–1597, doi:10.3762/bjoc.12.155

• diazoacetate (EDA) is relatively safe to handle, being thermally stable at room temperature with a reported half-life of 109 hours at 100 °C [3]. EDA is also stable in weakly acidic solutions such as glacial acid [4], but reactive in the presence of Lewis acids, a key property for its effectiveness in