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

• recycle because of their high boiling points. According to the Green Chemistry Principles, published in 1998 [10], processes have to be designed in order to “minimize the quantity of final waste and to avoid hazardous or toxic solvents”. Nanosponges themselves, nevertheless, are synthesized from starch

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

• material [55][56][57]. Flow chemistry also enables chemists to safely use hazardous gaseous reagents that are otherwise avoided, whilst simultaneously increasing the gas/liquid–gas/solid interfacial surface area which enhances reactivity [58][59][60][61]. This was highlighted by Noël and co-workers, who

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• variety of substrates, although the methodology required hazardous conditions; i.e., hot benzene [62]. A few years later, similar types of reactions were carried out by Loh and co-workers [63]. In this case, a variety of α,β-unsaturated compounds, that, rather than undergoing intramolecular cyclization

Copper-catalyzed O-alkenylation of phosphonates

• Nuria Vázquez-Galiñanes,
• Mariña Andón-Rodríguez,
• Patricia Gómez-Roibás and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2020, 16, 611–615, doi:10.3762/bjoc.16.56

• subject to selectivity problems, involve toxic and hazardous materials or are limited to the restricted availability of the corresponding phosphorus reagents. Therefore, the development of alternative methods for the synthesis of acyclic enol phosphonates is highly desirable. Diaryliodonium and aryl

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• yield the monobrominated products in excellent yields via visible-light photoredox catalysis (Scheme 20) [159]. Earlier literature reports suffered from the use of hazardous compounds (e.g., bromine) and low selectivities [160]. The reactive radical intermediates in their study were detected via laser

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

• excess of reagents, hazardous, flammable, or toxic reagents and high temperatures are required, which, in turn, may be detrimental to more highly functionalized starting materials. Nevertheless, this reaction under milder conditions is a valuable C–C bond-forming reaction for the preparation of β

• cyclohexyl 15 (68%) analogues. We were pleased to obtain the highly versatile and synthetically useful cinnamoylacetonitrile 17 [20] from renewable ethyl cinnamate in 64% yield, as this yield was comparable to more expensive and hazardous lithiation protocols [7]. Finally, we attempted method optimization

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

• have been developed towards Tamiflu to date [1][2][3]. However, most of these synthetic approaches suffer from the use of potentially hazardous azide chemistry, thus raising safety concerns [4] and eventually ruled out for large scale synthesis in batch systems [1][2]. The importance and use of azide

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

• high N/C-ratio might result in potential hazardous high energy materials, we herein investigated their thermal stability by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Results and Discussion We started our experiments with the preparation of appropriate λ3-iodanes

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Reaction of oxiranes with cyclodextrins under high-energy ball-milling conditions

• László Jicsinszky,
• Federica Calsolaro,
• Katia Martina,
• Fabio Bucciol,
• Maela Manzoli and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2019, 15, 1448–1459, doi:10.3762/bjoc.15.145

• solvent, its amount is limited, especially in parenteral applications [37]. Generally, 60–70% propylene oxide is utilized in the CD substitution reaction, which can result in 5–10% oligo-PG content in the crude product [6]. The hazardous nature of the reagent makes full conversion a necessity. The

Fabrication, characterization and adsorption properties of cucurbit[7]uril-functionalized polycaprolactone electrospun nanofibrous membranes

• Changzhong Chen,
• Fengbo Liu,
• Xiongzhi Zhang,
• Zhiyong Zhao and
• Simin Liu

Beilstein J. Org. Chem. 2019, 15, 992–999, doi:10.3762/bjoc.15.97

• present in the molecular structure. Combined with merits of host molecules and electrospun nanofibers, the supramolecular host functionalized nanofibers have been widely reported in recent years as efficient molecular filters and absorbent for the removal of hazardous chemicals or polluting substances. A

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• expensive, troublesome and capricious reagent, our improved synthesis of adefovir avoids this. As adenine is introduced later in our synthetic sequence, fewer steps are carried out in hazardous, environmentally harmful solvents such as DMF or NMP. Furthermore, the introduction of a more reactive

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

• ], dichloromethane and some catalyst such as para-toluenesulfonic acid [17]. Furthermore, most of them induce to manage undesirable waste produced in stoichiometric amounts. Recently, such synthetic methods utilizing hazardous solvents and reagents and generating toxic waste have become discouraged and there have

• of the twelve green chemistry principles: a cleaner and eco-friendly reaction profile with minimum of waste, solvent without negative environmental impact, shorter reaction time and safely work with a pressure tube canning prevent fires and emissions of hazardous compounds and toxic gas. (v) The

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• smaller volumes making them inherently safer. Due to low processing volumes and reactions at intrinsic rates without much of human intervention it is possible to carry out hazardous reactions and a reaction at much higher temperature which is not possible with conventional methods [22][23]. An automated

Mild and selective reduction of aldehydes utilising sodium dithionite under flow conditions

• Nicole C. Neyt and
• Darren L. Riley

Beilstein J. Org. Chem. 2018, 14, 1529–1536, doi:10.3762/bjoc.14.129

• laboratories because of its ease of use, safety and control [3][4][5][6]. Continuous flow technologies are generally more effective than traditional batch processes with key advantages including intensified heat and mass transfer, inline reaction monitoring, higher mass throughput, safer control of hazardous

2-Iodo-N-isopropyl-5-methoxybenzamide as a highly reactive and environmentally benign catalyst for alcohol oxidation

• Takayuki Yakura,
• Tomoya Fujiwara,
• Akihiro Yamada and
• Hisanori Nambu

Beilstein J. Org. Chem. 2018, 14, 971–978, doi:10.3762/bjoc.14.82

• fundamental and frequently used transformation in organic synthesis. Heavy metal-based oxidants such as chromium(VI), lead(IV), and mercury(II) have been extensively used for this purpose for a long time. However, these oxidants are highly toxic and produce hazardous waste. Recently, hypervalent iodine

Biocatalytic synthesis of the Green Note trans-2-hexenal in a continuous-flow microreactor

• Morten M. C. H. van Schie,
• Tiago Pedroso de Almeida,
• Gabriele Laudadio,
• Florian Tieves,
• Elena Fernández-Fueyo,
• Timothy Noël,
• Isabel W. C. E. Arends and
• Frank Hollmann

Beilstein J. Org. Chem. 2018, 14, 697–703, doi:10.3762/bjoc.14.58

• described in the literature to alleviate the inactivation issue described above [9][10][11][12]. The continuous-flow microreactor technology has emerged as a safe and scalable way to approach oxidation reactions [13][14]. Due to its small dimensions, hazardous reactions can be easily controlled, owing to

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• controlled products to potentially maximize conversion, smaller equipment footprint, and increased safety profiles when working with hazardous materials and reaction conditions [20]. These advantages often result in flow processes being significantly more efficient, as well as less costly, when compared to

Palladium-catalyzed ortho-halogenations of acetanilides with N-halosuccinimides via direct sp² C–H bond activation in ball mills

• Zi Liu,
• Hui Xu and
• Guan-Wu Wang

Beilstein J. Org. Chem. 2018, 14, 430–435, doi:10.3762/bjoc.14.31

• . China 10.3762/bjoc.14.31 Abstract A solvent-free palladium-catalyzed ortho-iodination of acetanilides using N-iodosuccinimide as the iodine source has been developed under ball-milling conditions. This present method avoids the use of hazardous organic solvents, high reaction temperature, and long

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• hazardous mycotoxins. Similar studies on other fungal cultures with proven initial antagonistic activities that can be related to VOCs will probably be rewarding. Total ion chromatogram of a representative headspace extract from Daldinia clavata MUCL 47436. Peak numbers refer to compound numbers in Scheme 2

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

• new entries into these valuable structures [6]. However, common to the majority of these indole syntheses is the use of hazardous entities such as hydrazines (Fischer), diazonium species (Japp–Klingemann) or azides (Hemetsberger–Knittel) or the necessity to construct specifically functionalised

Mechanically induced oxidation of alcohols to aldehydes and ketones in ambient air: Revisiting TEMPO-assisted oxidations

• Andrea Porcheddu,
• Evelina Colacino,
• Giancarlo Cravotto,
• Francesco Delogu and
• Lidia De Luca

Beilstein J. Org. Chem. 2017, 13, 2049–2055, doi:10.3762/bjoc.13.202

• to the respective carboxylic acid [11][12]. In addition, the appeal of this reaction is reduced by the need to use stoichiometric amounts of strong oxidising agents that are extremely toxic, hazardous, and expensive [13][14][15][16][17]. The use of the stable tetraalkylnitroxyl radical TEMPO (2,2,6,6

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• global warming, it is important to minimize the usage of hazardous chemicals in both academic and industrial research, elimination of waste, and possibly recycle them to obtain better results in greener fashion. The studies under the area of mechanochemistry which cover the grinding chemistry to ball

• ][83][84]. During the synthetic application of these molecules protection of -NH2 and -COOH group are needed. The traditional protection chemistry involves hazardous solvents, direct handling of corrosive reagents, longer reaction time, and tedious purification processes, etc. Therefore, methodologies

• reaction time, hazardous organic solvent, and tedious isolation procedure are implemented. Dekamin and co-workers have demonstrated the synthesis of pyrans using potassium phthalimide (POPI) as a catalyst under ball-milling which is found to be advantageous over solution phase synthesis [158]. Malonitrile

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

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

• equiv) for 40 minutes, followed by the click-coupling reaction of the second equivalent of an aniline with the intermediate isothiocyanate. In this way, non-symmetrical thioureas 25a–d were synthesized and isolated in high 87–94% yields. Instead of using thiophosgene and CS2 as corrosive and hazardous

Mechanochemical N-alkylation of imides

• Anamarija Briš,
• Mateja Đud and
• Davor Margetić

Beilstein J. Org. Chem. 2017, 13, 1745–1752, doi:10.3762/bjoc.13.169

• hazardous hydrazine hydrate was replaced by 1,2-diaminoethane [39] and conversion to the corresponding benzylamines was quantitative within 1 h. As a proof of concept of reaction, p-methylbenzylamine was isolated in 41% yield in the form of acetamide 42. In this way, a three-step, two-pot (A and B, Scheme 5