Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• standard reaction conditions with difluorocarbene precursor TMSCF2Br (2, 2.0 equiv), activator KFHF (4.0 equiv), and grinding auxiliary CsCl (4.0 equiv), difluoromethyl enol ether 3a was obtained after 90 min reaction time at 25 Hz in 74% yield, determined by quantitative 1H NMR spectroscopy (Table 1

• with too much of it, side reactions occurred [31][32][33]. Next, various grinding auxiliaries were investigated at a reaction time of 60 min (Table 1, entries 6–9). A similar yield of 3a (69%) was obtained with KCl or KBr instead of CsCl (Table 1, entries 6 and 7 versus entry 3). Using NaCl, gave 3a in

• sufficient mixing. Silica could not fulfill this role. Lastly, water, 1,4-dioxane, chloroform, and toluene were tested in a liquid-assisted grinding (LAG) protocol (Table 1, entries 10–13). The lowest yields were obtained with water and 1,4-dioxane, providing 3a in yields of 37% and 43%, respectively (Table

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• mixture of unreacted reagents was recovered. The observations indicate a significant role of factors related to the physical contact between substances, milling balls, and the walls of the grinding vessel on the final outcome of the reaction when the system is in a liquid state. Interestingly, the

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• past several decades [19][20][21][22]. The base-mediated solvent-free Cannizzaro reaction was achieved through various methods, such as by grinding reactants in mechanochemical approaches and/or solid-supported bases. Minimizing the use of hazardous solvents not only reduces environmental impact but

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• surfactant and silica as the carrier providing the most promising results. Solid grinding was also employed, removing the need for a solvent and accelerating the reaction rate to 20 minutes and product yields to 99% without the need for conventional heating. Replacement of the Lewis acid or the silica

• the C=O bond. Thus, an innovative approach on nanocatalysis was introduced, incorporating solid grinding in catalyst-free conditions with the challenge of a high catalyst loading and lack of aliphatic aldehydes or ketones being utilized as substrates for the formation of their respective BIMs [118

• ]. In 2021, this methodology was reiterated by Wu et al., who conducted the reaction in the exact same conditions, utilizing the ball milling technique, instead of solid grinding, which slightly reduced reaction times and the catalyst loading necessary from 500 mg to 300 mg [119]. The substrate scope

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• . Results and Discussion We found that a convenient way toward 6,8-di-tert-butyl-2-(arylamino)-3H-phenoxazin-3-ones 4 involves the short-term heating (30 min) of a molten mixture of 1 and an arylamine at 250 °C, followed by purification of the products by column chromatography. No preliminary grinding of

Optimizing reaction conditions for the light-driven hydrogen evolution in a loop photoreactor

• Pengcheng Li,
• Daniel Kowalczyk,
• Johannes Liessem,
• Mohamed M. Elnagar,
• Dariusz Mitoraj,
• Radim Beranek and
• Dirk Ziegenbalg

Beilstein J. Org. Chem. 2024, 20, 74–91, doi:10.3762/bjoc.20.9

• Supporting Information File 1, Figure S2b), while maintaining a continuous flow of N2 in the headspace through a septum. The resulting suspension exhibited a yellow/greenish color and was subsequently washed with deionized water 3–5 times, followed by drying at 70 °C overnight and grinding. The synthesized

Facile access to pyridinium-based bent aromatic amphiphiles: nonionic surface modification of nanocarbons in water

• Lorenzo Catti,
• Shinji Aoyama and
• Michito Yoshizawa

Beilstein J. Org. Chem. 2024, 20, 32–40, doi:10.3762/bjoc.20.5

• groups. Aromatic micelle (PA-CH3)n was furthermore found to be stable for at least six days at room temperature in the dark (see Figure S37 in Supporting Information File 1). Noncovalent encircling of various nanocarbons in water By employing a simple grinding–sonication protocol, various nanocarbons

• grinding (3 min) and sonication (30 min) protocol provided a clear yellow aqueous solution of (PA-OCH3)n·(g-C3N4)m. The formation of the host–guest structure was confirmed by UV–visible analysis, which showed a new absorption band around 312 nm (Figure 6b). This result showcased the ability of amphiphile

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• to reduce energy consumption and the carbon footprint. The traditional heating techniques used to synthesize compounds are being replaced by contemporary green alternative energy systems, such as photocatalysis, microwave irradiation, ultrasonic irradiation, grinding, and ball milling processes

Mechanochemical solid state synthesis of copper(I)/NHC complexes with K₃PO₄

• Ina Remy-Speckmann,
• Birte M. Zimmermann,
• Mahadeb Gorai,
• Martin Lerch and
• Johannes F. Teichert

Beilstein J. Org. Chem. 2023, 19, 440–447, doi:10.3762/bjoc.19.34

• approaches have in common that the conjugated acid of the added base is a liquid. In the literature, the improvement of mechanochemical syntheses by addition of small amounts of a liquid have been reported (LAG, liquid-assisted grinding) [43]. However, in our case, the formation of small amounts of liquid

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements

• Alexios I. Vicatos,
• Zakiena Hoossen and
• Mino R. Caira

Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184

• to prepare complexes by spray-drying, freeze-drying, co-grinding, kneading and solution-based crystallization; however, this modest type of ‘fingerprinting’ has not generally been pursued further to deduce important features of CD complexes such as the crystal packing of the CD host molecules

• kneading experiments (co-grinding of the respective hosts and guests with water as a medium), the complex identities being subsequently determined unequivocally by powder X-ray diffraction (PXRD). Authentic CD complex formation was deduced from close correlation between the angular peak positions of the

Dissecting Mechanochemistry III

• Lars Borchardt and
• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1454–1456, doi:10.3762/bjoc.18.150

• , Colombia 10.3762/bjoc.18.150 In the past ten years, the use of mechanochemical techniques (e.g., grinding, milling, extrusion, pulsed ultrasonication, resonant acoustic mixing, etc.) have widespread in the field of organic chemistry, enabling the development of new and more sustainable protocols for

• for the halogenation of organic substrates. For example, Banerjee and co-workers reported the mono-, di-, and trihalogenation of aromatics by controlling the stoichiometry of the N-halosuccinimide (NXS) and PEG-400 as the grinding auxiliary in a mechanical grinder (Scheme 1a) [3]. N-Halosuccinimides

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• , University of Illinois at Chicago, Chicago, Illinois 60612, United States 10.3762/bjoc.18.147 Abstract In this paper, we report the mechanochemical synthesis of unsymmetrical salens using grinding and ball milling technologies, respectively, both of which were afforded in good yield. The chelating effect of

• ]. Inspired by the mechanochemical chemistry technology to simplify chemical processes and eliminate the use of organic solvents, salen compounds have been synthesized by the “green” grinding strategy previously [30][31][32][33][34][35][36][37][38][39]. Herein, we report a one-pot two-step mechanochemical

• ), half equivalent of 5-bromo (Br‒), 5-methyl, 4-diethylamino (Et2N‒), 3,5-dichloro (Cl‒), or 3,5-di-tert-butyl (t-Bu‒) salicylaldehydes (red moieties in Scheme 2), and trace methanol, followed by grinding for 20 minutes for the second reaction step to complete, monitored by TLC. A trace amount of

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• mechanochemistry. However, in recent times, manual grinding and ball milling techniques (Figure 1b and Figure 1c) have also been used as alternatives to activate mechanophores incorporated in polymers. Such an application complements the original use of ball milling to generate mechanoradicals through homolytic

• ). Importantly, the BMPF mechanophore was also proven to be thermally stable up to 110 °C, which supports the conclusion that the mechanical force caused by the grinding was responsible for the activation of the BMPF mechanophores [28]. Comparative studies between ultrasound and ball milling have also

• also provided mounting evidence that ball milling and manual grinding, techniques typically used in small molecule mechanochemistry, could trigger chemical reactions in multimechanophore polymers [30], nonsymmetric mechanophores embedded in polymer systems [31], and mixtures of mechanochromic polymers

From amines to (form)amides: a simple and successful mechanochemical approach

• Federico Casti,
• Rita Mocci and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 1210–1216, doi:10.3762/bjoc.18.126

• ]. In general, mechanochemistry refers to studying solid-state chemical changes promoted by external mechanical energy, such as grinding or milling. A deeper understanding of its mechanistic aspects laid the basis for further growth in this topic, opening new routes to more efficient mechanochemical

• ). Switching to sodium sulfate as a grinding additive significantly enhanced the reaction performance (Table 1, entries 3 and 4). At this stage, we wondered, if using a more efficient dehydrating agent would be mandatory for the reaction to occur. Therefore, we turned our attention toward p-tosylimidazole (p

• efficiently took place even in the presence of a catalytic amount of p-Ts-Im without significant differences in the reactivity. This data led us to question the effective role of p-Ts-Im in promoting the formylation reaction, which could exploit its role as the sole solid auxiliary of grinding. p

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• catalyst-free halogenation of phenols and anilines via liquid-assisted grinding using PEG-400 as the grinding auxiliary. A series of mono-, di-, and tri-halogenated phenols and anilines was synthesized in good to excellent yields within 10–15 min in a chemoselective manner by controlling the stoichiometry

• reaction time, and mild reaction conditions are a few noticeable merits of this environmentally sustainable mechanochemical protocol. Keywords: automated grinding; chemoselectivity; mechanochemistry; N-bromosuccinimide; PEG-400; regioselectivity; stoichiometry-controlled halogenation; Introduction Aryl

• mechanical grinding or milling, has garnered massive interest among chemists owing to its green attributes like solvent-free, clean, atom economic, and time-efficient, and has been identified by the IUPAC as one of 10 world-changing technologies [47]. While milling has received more focus, the simpler form

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• dust. This combination of metals worked well, and the best conditions were obtained with the addition of a small amount of THF (liquid assisted grinding, LAG) [22], η = 0.5 μL·mg−1 (Table 1, entry 19). In contrast, the solution reaction catalyzed by Zn/Cu dust was totally ineffective (Table 1, entry 21

• ), even with the agitation by ultrasound (Table 1, entry 22). The ratios of side-products vary depending on the reaction conditions (Table S1, Supporting Information File 1). The endo-product 15 was dominant in the neat grinding experiment (Table 1, entry 1), whereas phthalimide 16 dominates when NaCl was

• employed as grinding auxiliary (Table 1, entries 2 and 4). The addition of ZnBr2 (which is formed in the reaction and postulated that it could facilitate the oxa-ring opening of 15 to 16) [13] did not notably increase the amount of phthalimide, indicating that rather deoxygenation leading to 16 is

A trustworthy mechanochemical route to isocyanides

• Francesco Basoccu,
• Federico Cuccu,
• Federico Casti,
• Rita Mocci,
• Claudia Fattuoni and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 732–737, doi:10.3762/bjoc.18.73

• mg of NaCl as a grinding auxiliary (0.5 h, 36 Hz, Table S1 in Supporting Information File 1). So, we then looked for a solid base to use in place of triethylamine, avoiding the use of further additives. Unluckily, neither solid inorganic bases such Na, K, and Cs carbonates [37], Mg and Ba oxides, nor

• are high for EDGs (2d,e), while from good to high for the EWGs (2b,c). To confirm what has been previously stated, isonitrile 2a was recovered in lower yields than compound 2e (Scheme 3). At the end of the reaction, adding 0.5 equivalents of water for a 15 minute grinding step was necessary to

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

• Dajana Barišić,
• Mario Pajić,
• Ivan Halasz,
• Darko Babić and
• Manda Ćurić

Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69

• using N-halosuccinimides as the halogen source under neat grinding or liquid-assisted grinding conditions in a ball mill has been described. Depending on the azobenzene substrate used, halogenation of the C–H bonds occurs in the absence or only in the presence of PdII catalysts. Insight into the

• -bromosuccinimide (NBS) under neat grinding (NG) and liquid-assisted grinding (LAG) conditions in a ball mill [51]. Insight into the dynamics of the formation of reaction intermediates and products was obtained by in situ Raman monitoring that provided information on the nature of the catalytically active PdII

• proceeds by electrophilic cleavage with neutral NBS or the hydrogen bond complex NBS∙∙∙TsOH as a bromine source. Here we present the mechanochemical selective halogenation of unsymmetrically substituted azobenzenes by NXS (X = Cl, Br, or I). The liquid-assisted grinding of para-halogenated derivatives of

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• conditions: reactants were milled at 21 Hz in a 25 mL milling jar containing one stainless-steel grinding ball (15 mm in diameter). Optimization of the reaction conditions.a Supporting Information Supporting Information File 46: Experimental details, characterization data, copies of NMR spectra and X-ray

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions

• José G. Hernández,
• Karen J. Ardila-Fierro,
• Dajana Barišić and
• Hervé Geneste

Beilstein J. Org. Chem. 2022, 18, 182–189, doi:10.3762/bjoc.18.20

• ; sulfonylation; Introduction Mechanosynthesis of organic molecules and materials using mechanochemical techniques such as ball milling, extrusion, grinding, etc. [1][2][3] have enabled the development of known and new chemical transformations in a more sustainable fashion [4]. Commonly, mechanochemical

In-depth characterization of self-healing polymers based on π–π interactions

• Josefine Meurer,
• Julian Hniopek,
• Johannes Ahner,
• Michael Schmitt,
• Jürgen Popp,
• Stefan Zechel,
• Kalina Peneva and
• Martin D. Hager

Beilstein J. Org. Chem. 2021, 17, 2496–2504, doi:10.3762/bjoc.17.166

• literature [31]. In the first step, the sample was hot pressed (at 150 °C, at about 2 t for 3 minutes) in a special manufactured mold. The pressed polymer samples were embedded in epoxy resin consisting of Epoxy Resin L and Hardener CL from R&G Faserverbundstoffe GmbH, followed by grinding of the sample with

Particle size effect in the mechanically assisted synthesis of β-cyclodextrin mesitylene sulfonate

• Stéphane Menuel,
• Sébastien Saitzek,
• Eric Monflier and
• Frédéric Hapiot

Beilstein J. Org. Chem. 2020, 16, 2598–2606, doi:10.3762/bjoc.16.211

• considerable attention as it may be unique in features to selectively direct the reaction pathway. In the continuation of our work on the synthesis of modified cyclodextrins (CDs) via mechanochemical activation, we sought to discriminate the contribution of supramolecular effects and grinding during the course

• the reaction. In this study, we show that grinding β-CD reduces the particles size over time down to a limit of 167 nm. The granulometric composition remains rather invariant for grinding times over 1 h. Each type of β-CD particles reacted with mesitylenesulfonyl chloride (MtsCl) to produce β-CDMts

• . Contrary to what could be intuitively anticipated, smaller particles did not lead to the highest conversions. The impact of grinding on the conversion was limited. Interestingly, the proportion of β-CDMts mono-substituted on the primary face significantly increased over time when the reaction was carried

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• reactions, and even in nanomaterials preparation [1][2][3][4][5]. Indeed, solid-state mechanochemical methodologies are a viable alternative to traditional syntheses in solution [4] for the preparation of complex molecules, either under solvent-free conditions, named ‘neat grinding’, or in nearly solvent

• -free conditions, e.g., liquid-assisted grinding (LAG), slurries, and homogenous solutions. Although there are compounds that can only be achieved by conventional solution-based methods, mechanochemistry offers some important advantages over conventional bulk synthesis. These advantages have become more

• by grinding Dex and 1 (in roughly equimolar amounts) at 25 Hz for 90 minutes, in a 10 mL mixer mills using one stainless-steel ball (∅ = 1.0 cm). The product, a red powder (Dex-1b, Scheme 1, route B), was easily recovered from the jar and solubilized in DMSO. Then, the conjugate (Dex-1b, Scheme 1

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

• drive and control chemical reactions, for example, using grinding or milling to transfer energy to chemical bonds [11]. Mechanochemical transformations are well established in inorganic chemistry and they are easily transferable to an industrial scale [12][13]. Mechanochemistry in organic chemistry

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