Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• agents for many years. However, these reagents have significant risks for safe handling. Although XeF2 [15] was considered as a safer alternative, it is expensive because of the scarcity of Xe in nature. The appearance of the safe and easy-to-handle N-F fluorinating agents described in this review have

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• commercial flow reactors allow for the safe simulation of larger scale processes within the lab environment, facilitating and expediting the process optimisation experience. While some of the implications of the flow chemistry are more obvious than others, i.e., greener processes with potential cost

Nitroalkene reduction in deep eutectic solvents promoted by BH₃NH₃

• Chiara Faverio,
• Monica Fiorenza Boselli,
• Patricia Camarero Gonzalez,
• Alessandra Puglisi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2021, 17, 1041–1047, doi:10.3762/bjoc.17.83

• safe as well as economically and environmentally sustainable alternative to the traditional organic solvents. Here, we report the combination of an atom-economic, very convenient and inexpensive reagent, such as BH3NH3, with bio-based eutectic mixtures as biorenewable solvents in the synthesis of

• whole research community concerned with the concept of a circular economy [3]. In this context, deep eutectic solvents (DESs) have attracted an increasing attention as green, safe, economically and environmentally sustainable alternative to the traditional organic solvents [4]. They are combinations of

• materials that can be used to form eutectic mixtures offers an incredibly high variety of combinations to generate new, safe and biodegradable DESs [5]. Another fundamental principle of green chemistry is the atom economy concept. In this context, ammonia borane (AB) is receiving increasing attention as

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• biguanides. This pathway is particularly convenient as cyanoguanidines are readily available, inexpensive, and safe [32]. Moreover, this reaction occurs with full atom economy and provides the desired biguanides with fairly high yields. A prior step of substituted cyanoguanidine preparation gives access to

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• this LNP formulation may not induce cytokine release syndrome in vivo [60][61]. Conclusion Taken together, we have shown that the LNP B9 formulation is safe, can traverse the BBB, and is readily taken up in multiple cell types. In the future, it will be interesting to explore whether increased uptake

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• monobutyltin oxide, using substoichiometric amounts of isosorbide and succinic acid and no solvent at 230 °C reaction temperature. Isosorbide is a safe chemical [246] that is obtainable on the large scale from renewable glucose [247][248]. Because of this and due to the inherent rigid structure, conferring the

• hydrogenolysis to give PD in 99% yield at 160 °C, 54 bar H2 and in anisole/THF solvent [182][188]. PD is a safe chemical that is mainly produced from propylene oxide or catalytically from lactic acid intermediate, and it serves in the polymer and food industry or as antifreezing agent [276][277]. Under milder

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• preparation of 2H-azirines and their stereoselective transformation into highly functionalized NH-aziridines, starting from vinyl azides and organolithium compounds. The protocol has been developed using cyclopentyl methyl ether (CPME) as an environmentally benign solvent, resulting into a sustainable, safe

• functionalized oxazoles using acetone as the solvent (Scheme 1c) [28]. Inspired by these recent reports, we became interested in the development of an eco-friendly strategy for the safe preparation of highly functionalized NH-aziridines from acyclic precursors. Herein, we report a sustainable mixed flow-batch

• proceed stereoselectively when organolithium compounds were added to 2,3-diphenyl-2H-azirine. This is a fast, safe, green and convenient method to access this interesting structural motif without requiring protection/deprotection steps or long synthetic pathways. Flow generation and transformation of 2H

Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives

• Emese Gal,
• Luiza Gaina,
• Hermina Petkes,
• Alexandra Pop,
• Castelia Cristea,
• Gabriel Barta,
• Dan Cristian Vodnar and
• Luminiţa Silaghi-Dumitrescu

Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242

• that the C-(hetero)aryl-α-(arylamino)acetonitrile derivatives can be considered genotoxically safe and possibly antimutagenic. Keywords: Ames test; α-aminoacetonitriles; ferrocene; phenothiazine; SEM; single crystal XRD; sonochemistry; Introduction Sonochemistry can be considered as a major

• -amino-C-substituted-acetonitriles pointed out that the compounds 2c, 2i, and 2l can be considered as genotoxically safe at concentrations in the range of their solubility limit in DMSO/water media. The tested compounds also exhibited antimutagenic activity by interfering with the effect of known

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2020, 16, 2862–2869, doi:10.3762/bjoc.16.235

• reaction for the synthesis of substituted dihydropyridines was performed under green heterogeneous and neat conditions in the presence of 0.04 g/mmol of a 40 wt % phosphotungstic acid on alumina catalyst, which is simple, safe and environmentally benign to prepare, fully recoverable, and reusable for up to

Dawn of a new era in industrial photochemistry: the scale-up of micro- and mesostructured photoreactors

• Emine Kayahan,
• Mathias Jacobs,
• Leen Braeken,
• Leen C.J. Thomassen,
• Simon Kuhn,
• Tom van Gerven and
• M. Enis Leblebici

Beilstein J. Org. Chem. 2020, 16, 2484–2504, doi:10.3762/bjoc.16.202

• -terpinene by utilizing singlet oxygen. The permeability of the fluoropolymer film to oxygen was utilized to supply oxygen to microcapillaries. The system was suggested to be used in combination with dangerous gases to ensure safe operational conditions. With the fluoropolymer microcapillaries, space time

• be determined in order to ensure safe operating conditions. Mass transport The mass transport phenomena can be quantified by the characteristic mixing time and the overall volumetric mass transfer coefficient. The characteristic mixing time in conventional reactors depends on many parameters, such as

A proposed sustainability index for synthesis plans based on input provenance and output fate: application to academic and industrial synthesis plans for vanillin as a case study

• John Andraos

Beilstein J. Org. Chem. 2020, 16, 2346–2362, doi:10.3762/bjoc.16.196

• patients; however, there will be a remaining fraction that will be destined as non-usable waste via natural excretion by the human body and more importantly via disposal by pharmacies when the medicine passes its recommended safe expiry date. The estimation of FVP will always rely on significant

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• ][178][179], renders their employment in synthesis problematic. The high demand for a safe, stable and highly reactive electrophilic fluorinating reagent prompted researchers to synthesize the first generation of electrophilic fluorination reagents, including fluoroxytrifluoromethane [180], fluorine

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• functionalities in target molecules for the synthesis of glycoconjugates. Based on the synthetic strategy described in this work (a common building block and Nap ether protection), we have already designed a route to MPLA, a clinically safe [30] monophosphoryl lipid A derivative with one phosphate group linked to

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• stability, non-flammability, and low volatility. These are mixtures usually obtained from the combination of 2 or 3 safe, inexpensive and nature-inspired components able to engage in reciprocal hydrogen-bond interactions, and that form fluids at a specified mixing ratio at the desired temperature. Owing to

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

• Esra Demir,
• Ozlem Sari,
• Yasin Çetinkaya,
• Ufuk Atmaca,
• Safiye Sağ Erdem and
• Murat Çelik

Beilstein J. Org. Chem. 2020, 16, 1805–1819, doi:10.3762/bjoc.16.148

• using a safe, inexpensive, metal-free reagent, a simple purification method and shorter reaction times via a one-pot reaction. The study presents a useful method for one-pot conversion of epoxides to protected 1,2-diols and 2-amino alcohols in one reaction. In the computational part of the study, the

Mechanochemical green synthesis of hyper-crosslinked cyclodextrin polymers

• Alberto Rubin Pedrazzo,
• Fabrizio Caldera,
• Marco Zanetti,
• Silvia Lucia Appleton,
• Nilesh Kumar Dhakar and
• Francesco Trotta

Beilstein J. Org. Chem. 2020, 16, 1554–1563, doi:10.3762/bjoc.16.127

• . Polysaccharides and, among them, starch derivatives such as cyclodextrins (CD), have recently emerged as they are safe, of low cost and biodegradable. Cyclodextrin nanosponges (CD-NS) are crosslinked cyclodextrin polymers characterized by a nanosized three-dimensional network. The reactive hydroxy groups of CDs

• , applied to organic syntheses and polymers has gained growing interest in recent years [14][15][16][17][18]. Mechanochemical syntheses are safe and represent efficient activation methods for greener processes, avoiding the use of solvents and reducing energy consumption. Recently, many examples for

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• demonstrated the safe use of gaseous CF3I as a reagent for the continuous flow PRC trifluoromethylation of 5-membered heterocycles, such as N-methylpyrrole (1, Scheme 1), with a high conversion and selectivity for the monofunctionalised product 2 [62]. The system achieved full conversion for a variety of

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• demonstrated that contrary to common belief: 1) BTMS itself led to the cleavage of tert-butyl carboxyesters, and 2) amines, a commonly used standard additives in the McKenna reaction were not generally safe and may promoted side reactions in the presence of certain functional groups. Besides that, we

Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

• functions in a safe and robust manner. It also demands to be low-cost in order to have any potential for real-world applications. In other words, to achieve the set goals, innovation is needed to reduce the complexity/expense of (1) pumps; (2) reactors; (3) valves; (4) fittings, and (5) chemical containers

• chemistry technologies and cartridges containing activated metals can solve most of these issues: (1) the use of activated magnesium powder packed in a column increases the reaction rate and facilitates safe separation of the metal and reagent solution; (2) an efficient heat transfer (a large surface area

Anthelmintic drug discovery: target identification, screening methods and the role of open science

• Frederick A. Partridge,
• Ruth Forman,
• Carole J. R. Bataille,
• Graham M. Wynne,
• Marina Nick,
• Angela J. Russell,
• Kathryn J. Else and
• David B. Sattelle

Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105

• drugs available for human treatment were initially developed as veterinary medicines. Effective and safe anthelmintic drugs can reduce prevalence, intensity and morbidity associated with STHs. Two main strategies for delivery exist: the management of diagnosed patients and preventative chemotherapy

• species in enantiomerically pure form. A clinical trial examining the bioavailability of orally dispersible tablets of levo-praziquantel has been completed [42], and a Phase III trial evaluating safety and efficacy is underway (NCT03845140). Oral PZQ is safe and efficacious against adult worms of all

• ) achieved cure rates (CR) of between 76–95% for different Schistosoma species and 63.5% for mixed S. haematobium and S. mansoni infections and mean egg reduction rates (ERR) between 86–95% [44]. However, although PZQ is safe and efficacious against adult worms, it is only given once, and as the drug does

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• reactions that are stereospecific, high-yielding, modular, wide in scope, executable under simple reaction conditions, conductable in safe or easily removable solvents, and that generate only nonoffensive byproducts. Of course, the classical Huisgen 1,3-dipolar cycloaddition does not fit into the above

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

• Panagiotis S. Gritzapis,
• Panayiotis C. Varras,
• Nikolaos-Panagiotis Andreou,
• Katerina R. Katsani,
• Konstantinos Dafnopoulos,
• George Psomas,
• Zisis V. Peitsinis,
• Alexandros E. Koumbis and
• Konstantina C. Fylaktakidou

Beilstein J. Org. Chem. 2020, 16, 337–350, doi:10.3762/bjoc.16.33

• classic DNA intercalator EB (Kb = 1.23 × 105 M−1) as previously reported [69]. The data obtained by the UV–vis spectroscopy studies most probably indicate the interaction of the compounds with CT DNA. However, the exact mode of binding is not safe to be proposed before more experimental data can be

Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors

• Man-Man Wang,
• Hao Huang,
• Lei Shu,
• Jian-Min Liu,
• Jian-Qiu Zhang,
• Yi-Le Yan and
• Da-Yong Zhang

Beilstein J. Org. Chem. 2020, 16, 233–247, doi:10.3762/bjoc.16.25

• , compound II4 was safe for weed control in maize fields at a rate of 150 g ai/ha, and was identified as the most potent candidate for a novel HPPD inhibitor herbicide. The compounds described herein may provide useful guidance for the design of new HPPD inhibiting herbicides and their modification

• various species and genera and providing a theoretical basis for the design of inhibitors that are highly selective and safe [2]. In plants, HPPD inhibitors competitively restrain HPPA from chelating to FeII. The production of plastoquinone is inhibited and phytoene is accumulated when the transformation

• , II4 was found to be safe for use on maize. These results suggest that compound II4 is a promising HPPD inhibiting herbicide candidate deserving of further optimization studies. Experimental The experimental details and analytical data for intermediates C to M and title compounds were given in

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• -toxic and environmentally safe. These reagents play a dual role, as they enhance the electrophilicity of nitriles, carbonyls and carbinols, and can also react irreversibly with water. Unlike PPA, a Brønsted acid incompatible with some acid-sensitive functionalities, PPE and PPSE are aprotic and mild