A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• -substituted carboxylic acid derivatives, in general, from cheap commercially available esters, and as such merited further investigation. We required a green, safe and scalable process for the facile production of O-unprotected hydroxylated β-hydroxynitrile 1 via trifunctionalized β-ketonitrile 2 by a direct

Acid-catalyzed rearrangements in arenes: interconversions in the quaterphenyl series

• Sarah L. Skraba-Joiner,
• Carter J. Holt and
• Richard P. Johnson

Beilstein J. Org. Chem. 2019, 15, 2655–2663, doi:10.3762/bjoc.15.258

• for each isomer. In these reactions, we attribute no special effect due to microwaves. This has been a subject of some debate in the literature [37][38]. As we have demonstrated earlier, the microwave reactor simply provides a safe and reliable way to heat samples with superacids at temperatures well

Safe and highly efficient adaptation of potentially explosive azide chemistry involved in the synthesis of Tamiflu using continuous-flow technology

• Cloudius R. Sagandira and
• Paul Watts

Beilstein J. Org. Chem. 2019, 15, 2577–2589, doi:10.3762/bjoc.15.251

• , more than 60 synthetic routes have been developed to date, however, most of the synthetic routes utilise the potentially hazardous azide chemistry making them not green, thus not amenable to easy scale up. Consequently, this study exclusively demonstrated safe and efficient handling of potentially

• explosive azide chemistry involved in a proposed Tamiflu route by taking advantage of the continuous-flow technology. The azide intermediates were safely synthesised in full conversions and >89% isolated yields. Keywords: azide chemistry; continuous flow synthesis; hazardous; safe; Tamiflu; Introduction

• chemistry [1][2]. Therefore, the development of alternative practical and safe processes for Tamiflu synthesis, which can be adapted at large scale is imperative. The safety concerns associated with the use of azide chemistry prompted the chemical community to develop azide-free synthetic routes [1][2][7

Thermal stability of N-heterocycle-stabilized iodanes – a systematic investigation

• Andreas Boelke,
• Yulia A. Vlasenko,
• Mekhman S. Yusubov,
• Boris J. Nachtsheim and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2019, 15, 2311–2318, doi:10.3762/bjoc.15.223

• )cyclic iodanes. Albeit aryl-λ3-iodanes are viewed as safe and stable under ambient temperatures, systematic thermal degradation studies of hypervalent iodine reagents are still rare. In 1992 Varvoglis and co-workers investigated the thermal degradation of a variety of aryl iodine(III) dicarboxylates into

• . However, even the triazoles 2, 3, and 5 can be considered as safe compounds, but still deserve a common precaution due to the narrow decomposition process. Pyrazoles 6 and 7 are thermally more stable (Tpeak = 168.9 and 196.5 °C) with a remarkably lower ΔHdec value. NH-pyrazole 6 shows the lowest ΔHdec

• , all diazoles are more stable and more reactive than the well-established benziodoxolone 1. It is also worth mentioning, that even the least stable NHI 5 can be still regarded as “safe” to use [31]. Further investigations are needed to fully capture the synthetic potential of these pseudocyclic NHIs

Isolation of fungi using the diffusion chamber device FIND technology

• Benjamin Libor,
• Henrik Harms,
• Stefan Kehraus,
• Ekaterina Egereva,
• Max Crüsemann and
• Gabriele M. König

Beilstein J. Org. Chem. 2019, 15, 2191–2203, doi:10.3762/bjoc.15.216

• . To guarantee that the device was sealed properly, commercial aquarium safe silicone without antifungal additive was applied to the edges. All materials and tools were sterilized by autoclaving or surface disinfection and the procedure was performed under the laminar airflow cabinet. The sample-loaded

• each other with six M3 hex bolt screws, sandwiching the central plate with the attached membranes between them. To ensure the devices seal commercial aquarium safe and antifungal-less silicone (Soudal) was applied to the edges of the device. The silicone was given time to dry and the device was

Click chemistry towards thermally reversible photochromic 4,5-bisthiazolyl-1,2,3-triazoles

• Chenxia Zhang,
• Kaori Morinaka,
• Mahmut Kose,
• Takashi Ubukata and
• Yasushi Yokoyama

Beilstein J. Org. Chem. 2019, 15, 2161–2169, doi:10.3762/bjoc.15.213

• convergent tendency of the substituents due to the electron-donating character of the methoxy groups in 2c and the electron-withdrawing character of the cyano groups in 3c. However, it is safe to say the cyano groups in 3c are pulling the electrons and this effect reaches the nitrogen atom bearing the benzyl

Metal-free mechanochemical oxidations in Ertalyte^® jars

• Andrea Porcheddu,
• Francesco Delogu,
• Lidia De Luca,
• Claudia Fattuoni and
• Evelina Colacino

Beilstein J. Org. Chem. 2019, 15, 1786–1794, doi:10.3762/bjoc.15.172

• successfully used to induce mechanochemical oxidative processes on several structurally different primary and secondary alcohols. The proposed redox process is safe, inexpensive and performing effectively, especially on the macroscale. Herein, an Ertalyte® jar has been successfully used, for the first time, in

• with the unprecedented utilization of Ertalyte® jars, the mechanical activation allows obtaining the oxidized products from a broad spectrum of initial substrates. We show that the proposed mechanochemical method is definitely safe, performing effectively and inexpensive, thus providing an interesting

• the previously described shortcomings. As of 2013, this reagent is commercially available [63], inexpensive and sufficiently stable and safe for potential applications in mechanochemistry (Figure S1a, Supporting Information File 1) [64][65][66][67]. Once the most promising oxidant was identified

Efficiency Eff_syn of complex syntheses as multicomponent reactions, its algorithm and calculations based on concrete criteria

• Heiner Eckert

Beilstein J. Org. Chem. 2019, 15, 1425–1433, doi:10.3762/bjoc.15.142

• outstanding. Product purification is usually simple. All this reduces waste to a minimum. Due to the very weak negative reaction enthalpies, MCRs are also usually safe processes. The shortening of the synthesis through drastic reduction of the number of steps n leads to a strong waste prevention, which can be

Mechanochemical synthesis of poly(trimethylene carbonate)s: an example of rate acceleration

• Sora Park and
• Jeung Gon Kim

Beilstein J. Org. Chem. 2019, 15, 963–970, doi:10.3762/bjoc.15.93

• polymerization of cyclic carbonates, such as trimethylene carbonate (TMC) and its derivatives have been used for the controlled synthesis of high-molecular weight polymers. Among many catalysts, organocatalysts have attracted considerable attention, since the use of nontoxic catalysts warrants a safe use in

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• found to be safe after administration into the footpad of mice and demonstrated a similar response to α-1,2-trimannose-coated latex beads during L. major footpad infection. Furthermore, the bioerodible microparticles allowed for investigation of the role of pathogen-associated oligosaccharides for

• development of safe, efficacious and inexpensive alternatives to current therapeutics is needed. Understanding the mechanisms by which Leishmania regulates host immune responses are crucial for the development of vaccines, which may induce adaptive immunity that may prove beneficial for combating other

• infected trimannose treated wild-type mice in both the latex bead 1 and bioerodible microparticle 2 studies suggests that the new trimannose-linked bioerodible microparticles 2 are a safe and viable tool for presenting glycodendrimers to mammalian immune systems. The new construct of the bioerodible

Low-budget 3D-printed equipment for continuous flow reactions

• Jochen M. Neumaier,
• Amiera Madani,
• Thomas Klein and
• Thomas Ziegler

Beilstein J. Org. Chem. 2019, 15, 558–566, doi:10.3762/bjoc.15.50

• to the inner roughness of the channels [28]. Our design allows for a flexible change via CAD software in a few minutes. For instance, adding more inlet ports or altering the channel dimensions. The modified reactor can be printed in a few hours. We also optimized the way how to establish a safe and

A convenient and practical synthesis of β-diketones bearing linear perfluorinated alkyl groups and a 2-thienyl moiety

• Ilya V. Taydakov,
• Yuliya M. Kreshchenova and
• Ekaterina P. Dolotova

Beilstein J. Org. Chem. 2018, 14, 3106–3111, doi:10.3762/bjoc.14.290

• molar ratio of ketone, ester and NaH was found to be 1:1:2. The excess NaH acts as an alcohol and water scavenger, thus making the synthetic protocol more robust. Commercial NaH is supplied in a relatively safe form of 60% dispersion in mineral oil. Although other researchers recommended to use this

• mentioned before, an excess of NaH was used to improve the yields of diketones. It must be decomposed by careful addition of an anhydrous alcohol (MeOH or EtOH) before treatment of the reaction mixture with an aqueous acid. With this precaution, the whole synthetic procedure is safe. The results of the

Green synthesis of new chiral 1-(arylamino)imidazo[2,1-a]isoindole-2,5-diones from the corresponding α-amino acid arylhydrazides in aqueous medium

• Nadia Bouzayani,
• Jamil Kraїem,
• Sylvain Marque,
• Yakdhane Kacem,
• Abel Carlin-Sinclair,
• Jérôme Marrot and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2018, 14, 2923–2930, doi:10.3762/bjoc.14.271

• directed toward the development of environmentally safe conditions for the synthesis of heterocyclic compounds starting from natural (L)-α-amino acids [19][20][21][22][23] and the reactivity of α-amino acid phenylhydrazides [24][25], we now report a green and eco-friendly procedure for the synthesis of new

• conditions, we investigated the reaction in nontoxic solvents such as water and dimethyl carbonate (DMC). Indeed, DMC is well-known as safe reagent and solvent that has been used for many green applications [31][32][33]. On the other hand, water is a simply and environmentally benign solvent and interest has

• were obtained in this case. Interestingly, acidic (phenolic 5j) and basic moieties (as indolyl 5i) on the amino acid residue did not affect the selectivity. Conclusion In summary, we have developed environmentally safe conditions for the synthesis of new chiral 1-(arylamino)-1H-imidazo[2,1-a]isoindole

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• antibiotic-insensitive strains, the steady decline in the number of new antibacterial drugs and the insufficient investment in antimicrobial research and development (R&D) by the major pharmaceutical companies have led to a global health crisis in which the prospect of a future without a safe and effective

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• aqueous solution is probably well recognized in the literature. Less corrosive and toxic effects and the lack of dangerous vapors make it safe to handle under normal conditions. MSA as a biodegradable chemical is decomposed within 28 days by living organisms and is part of the natural sulfur cycle. During

Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• to AB in the presence of GSH and iodoacetic acid in phosphoric acid–citric acid buffer at 37 °C, a safe and eco-friendly detoxification of inorganic arsenics was developed via methyl transfer reactions mediated by biomimetic vitamin B12. 4. Dehalogenation reactions “Dehalorespiration” is also a model

A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

• Katherine E. Jolley,
• Michael R. Chapman and
• A. John Blacker

Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196

• Information File 1, S2). A maximum safe operating temperature of 110 °C was implemented to avoid thermal decomposition and thermal runaway. The direct reaction of N-chloramine 11, or the benzyl-substituted variant 12, led to a single regioisomer of the amine product in a lower reaction time than the analogous

Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester

• Takao Shoji,
• Hiroki Fukutomi,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 1946–1955, doi:10.3762/bjoc.14.169

• linkages that can be formed between native functional groups would be safe alternatives, and are known as natural conjugates such as nucleopeptides and nucleolipids [49]. We have been developing alkyl chain soluble support (ACSS)-assisted liquid-phase methods, specifically for peptide and oligonucleotide

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• under mild conditions [78]. The authors proposed a radical pathway involving the in situ generation of Br2, which opens the avenue for a reliable, ecologically benign, and safe dibromination method. Conclusion In the last two decades, great progress was made in hypervalent iodine(III) catalytic systems

Drug targeting to decrease cardiotoxicity – determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells

• Livia Polgár,
• Eszter Lajkó,
• Pál Soós,
• Orsolya Láng,
• Marilena Manea,
• Béla Merkely,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 1583–1594, doi:10.3762/bjoc.14.136

• HMC or on HUVEC cells, it might be a promising and safe candidate for targeted therapy. None of the conjugates (12–15) containing two drug molecules, independent on their type (Dau, Mtx) or attachment site, showed cytotoxicity on any of the tested cell types. The two Dau containing conjugates (12, 14

Direct electrochemical generation of organic carbonates by dehydrogenative coupling

• Tile Gieshoff,
• Vinh Trieu,
• Jan Heijl and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2018, 14, 1578–1582, doi:10.3762/bjoc.14.135

• polymer formation with less reactive epoxides (other than ethylene oxide) [7][8][9][10]. Electrochemistry has the capability to access products by extraordinary reaction pathways. Electric current is an inexpensive reagent and inherently safe reaction set-ups ensure a resource saving and applicable

Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• effects, there is a need to develop suitable delivery vectors for the safe transport of drugs to the nucleus. Such nuclear-targeting sequences have already proven to be successful delivery tools. According to their often basic nature, they are also able to traverse the cellular membrane [8]. Based on this

Selective carboxylation of reactive benzylic C–H bonds by a hypervalent iodine(III)/inorganic bromide oxidation system

• Toshifumi Dohi,
• Shohei Ueda,
• Kosuke Iwasaki,
• Yusuke Tsunoda,
• Koji Morimoto and
• Yasuyuki Kita

Beilstein J. Org. Chem. 2018, 14, 1087–1094, doi:10.3762/bjoc.14.94

• , reports aimed at realizing efficient and selective metal-free C(sp3)–H transformations are rather limited; however, investigations by several research groups are still ongoing [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Hypervalent iodine reagents are now widely accepted as a safe

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

Volatiles from three genome sequenced fungi from the genus Aspergillus

• Jeroen S. Dickschat,
• Ersin Celik and
• Nelson L. Brock

Beilstein J. Org. Chem. 2018, 14, 900–910, doi:10.3762/bjoc.14.77

• genus comprising several hundreds of known species. Some of these species are human pathogens, e.g., Aspergillus fumigatus can cause infections especially in immunocompromised patients, while other species are safe, e.g., Aspergillus oryzae is traditionally used in Japanese sake brewing. The genus has a