Mechanochemical amorphization of chitin: impact of apparatus material on performance and contamination

• Thomas Di Nardo and
• Audrey Moores

Beilstein J. Org. Chem. 2019, 15, 1217–1225, doi:10.3762/bjoc.15.119

• : amorphization; biomass; chitin; hardness; mechanochemistry; metal contamination; Introduction The last decade has seen a tremendous development in the field of mechanochemistry, which was notably covered in the New York Times in 2016 [1]. Yet, mechanochemistry is hardly a novel concept, since it is likely

• siliceous rock against pyrite [2][3]. Mechanochemistry comes with intrinsic advantages associated with the lack of solvent use during reaction, thus largely reducing the generation of waste [4] even in active pharmaceutical ingredient synthesis [5]. Yet mechanochemistry also allows the production of novel

• , with the specific reaction kinetic parameters [33]. There is, however, an interest in investigating these aspects further. In particular, it would be interesting to track the role of parameters such as ball size and mass on the progress of the reaction. In mechanochemistry, it is accepted that chemical

Mechanochemical synthesis of hyper-crosslinked polymers: influences on their pore structure and adsorption behaviour for organic vapors

• Sven Grätz,
• Sebastian Zink,
• Hanna Kraffczyk,
• Marcus Rose and
• Lars Borchardt

Beilstein J. Org. Chem. 2019, 15, 1154–1161, doi:10.3762/bjoc.15.112

• sorption experiments with benzene and cyclohexane. Keywords: hyper-crosslinked polymers; mechanochemistry; microporous; solvent-free; vapor sorption; Introduction The widespread use of microporous materials in areas like gas storage, gas separation, and catalysis has led to the development of a wide

• recent past it has been shown that for reactions, where the solubility of the reactants or products is an issue, mechanochemistry – a field which is currently gaining momentum – can be a promising workaround [12][13][14][15][16][17][18][19][20]. It has already been established as a versatile tool for the

• synthesis of several porous materials [21][22][23][24][25][26][27][28][29] and polymers [30][31][32][33][34][35][36][37][38][39][40][41][42]. In this contribution, we employed mechanochemistry for a protocol for the solvent-free crosslinking of HCP (Figure 1). This is supported by an investigation of

Extending mechanochemical porphyrin synthesis to bulkier aromatics: tetramesitylporphyrin

• Qiwen Su and
• Tamara D. Hamilton

Beilstein J. Org. Chem. 2019, 15, 1149–1153, doi:10.3762/bjoc.15.111

• -positions have been historically difficult in porphyrin synthesis, presumably owing to steric hindrance around the reactive site. We have used mechanochemistry for the simple, room-temperature synthesis of tetra-meso-substituted porphyrins. In the present study, mesitaldehyde undergoes acid-catalyzed

• methods. Yields of the mechanochemical synthesis were found to increase slightly upon longer exposure to an organic oxidizing agent in solution. This indicates that the mechanochemical condensation step may be more successful than initially realized. This work shows that mechanochemistry is a successful

• , simple, room-temperature method for producing tetra-meso-substituted porphyrins with bulky substituents. Keywords: condensation; grinding; mechanochemistry; milling; porphyrin; sterically-hindered; Introduction Porphyrins and related macrocycles such as chlorins, corroles, and bacteriochlorins carry

Unexpected polymorphism during a catalyzed mechanochemical Knoevenagel condensation

• Sebastian Haferkamp,
• Andrea Paul,
• Adam A. L. Michalchuk and
• Franziska Emmerling

Beilstein J. Org. Chem. 2019, 15, 1141–1148, doi:10.3762/bjoc.15.110

• monitoring multi-phase reactions during ball milling. Keywords: ball milling; C–C coupling; in situ; mechanochemistry; multivariate data analysis; Introduction Mechanochemistry offers a wide array of applications. It is used widely for synthesis of inorganic, metal-organic, and organic molecules and

• materials [1]. Interest in these methods stems largely from the fact that they are efficient and more environmentally friendly as compared to traditional approaches [2][3]. Mechanochemistry is a well-established method for the synthesis of coordination polymers, the formation of cocrystals, and in C–C

• coupling reactions [4][5][6][7]. Despite the increasing use of mechanochemistry, there is still a lack in understanding of the underlying processes involved during mechanically-facilitated reactions. This is particularly true of the potential role of transient polymorphic phases [8] and seeding effects [9

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

• can now be obtained through green mechanochemical synthesis. In addition to the general merits of mechanochemistry, such as being solvent-free and resulting in high conversions, we herein explore rate acceleration under ball-milling conditions while the conventional solution-state synthesis suffer

• important for chain-length control. Liquid-assisted grinding was applied for the synthesis of high molecular weight polymers, but it failed to protect the polymer chain from mechanical degradation. Keywords: aliphatic polycarbonate; green polymerization; mechanochemistry; organocatalyst; poly(trimethylene

• achieved by solution synthesis occur, which makes mechanochemistry a topic of rigorous research [6]. In the area of polymer chemistry, the use of mechanical forces has a long history. Strong mechanical forces can break covalent bonds, including strong C–C bonds, thus their utilization has generally focused

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• . Contrastingly, achieving syntheses through mechanochemical methods are generally time-saving, environmentally friendly and more economical. This review is written to shed some light on supramolecular chemistry and the synthesis of various supramolecules through mechanochemistry. Keywords: ball milling

• ; mechanochemistry; self-assembly; solvent-free; supramolecular; Introduction In living systems an important aspect is to create complex functional molecules from simpler units by following biomolecular mechanisms [1]. The biological assemblies for living beings are developed from processes of spontaneous self

• by NMR (Figure 20). When ClO4− has been used as the anion template, the formation of the eight-membered macrocycle cycHC[8] 36 was observed in 98% conversion by NMR after 30 min of LAG, followed by aging for one day at 60 °C [90]. Template-assisted mechanochemistry It was long believed that covalent

Synthesis of acylglycerol derivatives by mechanochemistry

• Karen J. Ardila-Fierro,
• Andrij Pich,
• Marc Spehr,
• José G. Hernández and
• Carsten Bolm

Beilstein J. Org. Chem. 2019, 15, 811–817, doi:10.3762/bjoc.15.78

• , mechanosynthesis of lipids by ball milling techniques has remained essentially unexplored. In this work, a multistep synthetic route to access mono- and diacylglycerol derivatives by mechanochemistry has been realized, including the synthesis of diacylglycerol-coumarin conjugates. Keywords: ball mill; coumarin

• ; diacylglycerols; lipids; mechanochemistry; Introduction In addition to being guided by chemical signals, cells respond to mechanical cues by sensing and transducing external mechanical inputs into biochemical and electrical signals [1]. Consequently, every time a cell is subjected to mechanical loads, the

• relevant building blocks with mechanochemistry has further been shown by the recent mechanochemical protocols to transform nucleoside and nucleotide substrates (Figure 1) [18][19]. On the other hand, reports on mechanochemical protocols for the synthesis or derivatization of lipids are scarce [20][21

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• without the use of metals. Salicylaldehydes with a high melting point or low solubility proved difficult to convert to the intermediate 3-nitrochromene derivatives [15]. In this regard, applying mechanochemistry has been proven previously to be a viable alternative [43]. To the best of our knowledge, both

Thiocarbonyl-enabled ferrocene C–H nitrogenation by cobalt(III) catalysis: thermal and mechanochemical

• Santhivardhana Reddy Yetra,
• Zhigao Shen,
• Hui Wang and
• Lutz Ackermann

Beilstein J. Org. Chem. 2018, 14, 1546–1553, doi:10.3762/bjoc.14.131

• manifold. Keywords: amidation; C–H activation; cobalt; ferrocene; mechanochemistry; Introduction C–H activation has surfaced as a transformative tool in molecular sciences [1][2][3][4][5][6][7][8][9]. While major advances have been accomplished with precious 4d transition metals, recent focus has shifted

• thermal fashion as well as by means of mechanochemistry, providing access to synthetically meaningful aminoketones. Selected ferrocene-based ligands and organocatalysts. Scope of substituted dioxazolones 2. C–H Amidation of arylated ferrocenes 1. Thiocarbonyl-assisted C–H amidation. H/D Exchange reactions

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• . Mechanochemistry has also found recent attention in materials chemistry and API formulation during which rearrangement of non-covalent interactions give rise to functional products. However, this has been known to nucleic acids science almost since its inception in the late nineteenth century when Miescher

• substrates on preparative scales. A survey of these reactions is provided, the majority of which have used a mixer ball mill and display an almost universal requirement for liquid to be present within the grinding vessel. Mechanochemistry of charged nucleotide substrates, in particular, provides considerable

• contribution of mechanochemistry (and specifically, ball milling) to the isolation of biologically active materials derived from nuclei by grinding will also be outlined. Finally non-covalent associative processes involving nucleic acids and related materials using mechanochemistry will be described

Bromide-assisted chemoselective Heck reaction of 3-bromoindazoles under high-speed ball-milling conditions: synthesis of axitinib

• Jingbo Yu,
• Zikun Hong,
• Xinjie Yang,
• Yu Jiang,
• Zhijiang Jiang and
• Weike Su

Beilstein J. Org. Chem. 2018, 14, 786–795, doi:10.3762/bjoc.14.66

• [33][34] and axitinib [35][36][37][38] (Scheme 1). Mechanochemistry as a burgeoning technique to promote solvent-free reactions has led to remarkable advances [39][40][41][42], particularly for cross-coupling reactions [43][44][45], involving Heck coupling with the aid of stoichiometric amounts of

• diameter (dMB), which usually play important roles in mechanochemistry processes [57][58][59][60]. First, the combined effect between ball-milling time and rotation speed was screened systematically (Figure 2). The results show a sharp increase of the product yield when elevating the rotation speed from

• protocol was conducted in a total mechanosynthesis of axitinib in short reaction time and high efficiency. With this system, we hope to expand the pharmaceutical synthetic toolbox in mechanochemistry. Investigation of additives in the Heck reaction: 1a (1.5 mmol), 2a (2.25 mmol), Pd(OAc)2 (5 mol %), PPh3

Liquid-assisted grinding and ion pairing regulates percentage conversion and diastereoselectivity of the Wittig reaction under mechanochemical conditions

• Kendra Leahy Denlinger,
• Lianna Ortiz-Trankina,
• Preston Carr,
• Kingsley Benson,
• Daniel C. Waddell and
• James Mack

Beilstein J. Org. Chem. 2018, 14, 688–696, doi:10.3762/bjoc.14.57

• Kendra Leahy Denlinger Lianna Ortiz-Trankina Preston Carr Kingsley Benson Daniel C. Waddell James Mack Department of Chemistry, University of Cincinnati, PO Box 210172, Cincinnati, OH 45221-0172, USA 10.3762/bjoc.14.57 Abstract Mechanochemistry is maturing as a discipline and continuing to grow

• the Wittig reaction. Keywords: green chemistry; high-speed ball milling; HSBM; LAG; liquid-assisted grinding; Wittig; Introduction Mechanochemistry is maturing as a discipline and continuing to develop and grow [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Thus it is important to continue

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

• corresponding N-halosuccinimides. Keywords: acetanilide; ball milling; C–H activation; halogenation; mechanochemistry; N-halosuccinimide; palladium catalysis; Introduction Aryl halides have been widely utilized in organic syntheses, which give access to a range of complex natural products [1][2]. However

• -bromosuccinimide (NBS) and N-iodosuccinimide (NIS), respectively, as the halogen source [30]. However, the mechanochemical ortho-halogenation using the cheaper palladium catalysts has not been reported yet. In continuing our interest in mechanochemistry [21][22][39][40][41] and C–H activation reactions [42][43][44

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

• Vania Andre Silvia Quaresma Joao Luis Ferreira da Silva M. Teresa Duarte Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal 10.3762/bjoc.13.239 Abstract Mechanochemistry is a powerful and environmentally friendly synthetic

• application in the pharmaceutical field (BioMOFs), whose importance has been growing and is now assuming a relevant and promising domain. The need to find cleaner, greener and more energy and material-efficient synthetic procedures led to the use of mechanochemistry into the synthesis of BioMOFs. Keywords

• : BioMOFs; drugs; green chemistry; mechanochemistry; organic based materials; Introduction Mechanochemistry is a straightforward and clean technique by which the desired products are obtained in high purity and high or quantitative yield. It combines high reaction efficiency with a minimum input of energy

Mechanochemistry

• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 2372–2373, doi:10.3762/bjoc.13.234

• Jose G. Hernandez Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany 10.3762/bjoc.13.234 Keywords: green chemistry; mechanochemistry; organic chemistry; solvent-free; The scientific community’s general interest in using mechanical energy to trigger or

• consumption, absence of external heating, fast reactivity, etc.). When compared with other, more established alternatives to carry out chemical transformations, mechanochemistry can still be considered as a nascent approach. Therefore, Thematic Series like this one gathers works from experts on the topic to

• encourage the chemistry community to adopt the concepts of mechanochemistry, and secondly, it strengthens the field. In addition to the previous special issues dedicated to mechanochemistry published in other peer-reviewed scientific journals [1][2], the Beilstein Journal of Organic Chemistry sought to host

Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole

• Martina Tireli,
• Silvija Maračić,
• Stipe Lukin,
• Marina Juribašić Kulcsár,
• Dijana Žilić,
• Mario Cetina,
• Ivan Halasz,
• Silvana Raić-Malić and
• Krunoslav Užarević

Beilstein J. Org. Chem. 2017, 13, 2352–2363, doi:10.3762/bjoc.13.232

• spin resonance (ESR) spectroscopy; in situ Raman monitoring; mechanochemistry; quinoline; solid-state click chemistry; Introduction The copper-catalyzed azide–alkyne cycloaddition (CuAAC) represents a prime example of click chemistry. Click chemistry describes “a set of near-perfect” reactions [1] for

• , there is a persistent incentive to find greener alternatives, which would reduce time and energy requirements as well as waste generated by these reactions. Among other non-conventional approaches such as microwave and ultrasound irradiation [7][12][13], mechanochemistry has emerged as a viable approach

• for CuAAC. In a broader sense, mechanochemistry, i.e., chemical transformations induced by mechanical force [14], has been rapidly advancing in various fields of synthesis and materials sciences, including inorganic [15], organic [16][17] and supramolecular materials [18][19], intermetallic compounds

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• explained by DFT calculations. Using this method, an enantiopure disubstituted Pro–Pro diketopiperazine was synthesized in 4 steps, making 5 new bonds using a ball mill. Keywords: ball mill; DFT calculations; diketopiperazine; mechanochemistry; pyrrolidine; Introduction 2,5-Diketopiperazines (DKPs) are

• groups on the Pro–Pro-based framework [17]. Recently, mechanochemistry has become a powerful synthetic technique for making new organic molecules [18][19]. In the course of this project, we applied mechanochemistry to a nucleophilic substitution and the efficient coupling of two proline residues. Results

The effect of milling frequency on a mechanochemical organic reaction monitored by in situ Raman spectroscopy

• Patrick A. Julien,
• Ivani Malvestiti and
• Tomislav Friščić

Beilstein J. Org. Chem. 2017, 13, 2160–2168, doi:10.3762/bjoc.13.216

• : green chemistry; mechanism; mechanochemistry; milling; monitoring; Raman spectroscopy; Introduction Over the past decade, mechanochemical reactions [1][2][3][4], i.e., chemical transformations induced or sustained through the application of mechanical force in the form of grinding, milling and shearing

• ] has rendered mechanochemical reactions by ball milling or grinding as viable, highly environmentally-friendly alternatives to solution-based chemistry. Importantly, mechanochemistry provides not only a means to conduct chemical transformations of poorly soluble reagents [17], but also enables access

• to reactions that are difficult or even impossible to achieve in solution [18][19][20], and allows the synthesis of molecular targets that have so far been considered impossible to synthesize [21] or isolate [22]. However, in contrast to rapid expansion of applications of mechanochemistry, the

Correction: Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 2128–2130, doi:10.3762/bjoc.13.210

• . Universidad 1001, Cuernavaca, Morelos, 62210, Mexico El Colegio Nacional, Luis Gonzáles Obregón 23, Centro Histórico, Ciudad de México, 06020, Mexico 10.3762/bjoc.13.210 Keywords: ball-milling; β3-amino acid; Candida antarctica lipase B; enzymatic resolution; mechanochemistry; The original published Tables

Peptide synthesis: ball-milling, in solution, or on solid support, what is the best strategy?

• Ophélie Maurin,
• Pascal Verdié,
• Gilles Subra,
• Frédéric Lamaty,
• Jean Martinez and
• Thomas-Xavier Métro

Beilstein J. Org. Chem. 2017, 13, 2087–2093, doi:10.3762/bjoc.13.206

• build more efficient and sustainable peptide syntheses in the near future. Keywords: ball-mill; green chemistry; mechanochemistry; peptide synthesis; SPPS; Introduction Peptides play a central role both in biological mechanisms and in therapeutic solutions of the future [1][2]. Pharmaceutical

Main group mechanochemistry

• Agota A. Gečiauskaitė and
• Felipe García

Beilstein J. Org. Chem. 2017, 13, 2068–2077, doi:10.3762/bjoc.13.204

• Agota A. Geciauskaite Felipe Garcia Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, 21 Nanyang Link, 637371, Singapore 10.3762/bjoc.13.204 Abstract Over the past decade, mechanochemistry has emerged as a powerful methodology in the search for

• sustainable alternatives to conventional solvent-based synthetic routes. Mechanochemistry has already been successfully applied to the synthesis of active pharmaceutical ingredients (APIs), organic compounds, metal oxides, coordination compounds and organometallic complexes. In the main group arena, examples

• of synthetic mechanochemical methodologies, whilst still relatively sporadic, are on the rise. This short review provides an overview of recent advances and achievements in this area that further validate mechanochemistry as a credible alternative to solution-based methods for the synthesis of main

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

• reaction exhibited higher yields and rates than the classical, homogeneous, TEMPO-based oxidation. Keywords: aldehydes; ball milling; ketones; mechanochemistry; oxidation reactions; TEMPO; Introduction Aldehydes and ketones constitute some of the most powerful and versatile building blocks that are

• , a thin historical thread twisting across human history connects powder metallurgy and mineralurgy with science and engineering at the cutting edge of research in the fields of materials science and chemistry [59]. Presently, mechanochemistry is one of the fastest growing areas of investigation that

• aims to provide alternative methods to traditional syntheses in organic and inorganic chemistry [49][60][61]. Mechanochemistry is also used in supramolecular chemistry [62] and metal-organic chemistry [63]. In this work, we show that mechanical processing by ball milling can represent a viable solution

Mechanochemical Knoevenagel condensation investigated in situ

• Sebastian Haferkamp,
• Franziska Fischer,
• Werner Kraus and
• Franziska Emmerling

Beilstein J. Org. Chem. 2017, 13, 2010–2014, doi:10.3762/bjoc.13.197

• process both result in crystalline products suitable for single crystal X-ray diffraction. Keywords: ball milling; C–C coupling; in situ; Knoevenagel condensation; mechanochemistry; Introduction Mechanochemical syntheses have gained increasing popularity in different areas such as materials science

• , chemistry, and pharmacy. Especially for organic syntheses, mechanochemistry is currently implemented as a green, fast, and efficient synthesis approach [1][2][3]. The syntheses are either solvent-free or require only a minimum amount of solvent. Consequently, solvation and desolvation phenomena can be

New bio-nanocomposites based on iron oxides and polysaccharides applied to oxidation and alkylation reactions

• Daily Rodríguez-Padrón,
• Alina M. Balu,
• Antonio A. Romero and
• Rafael Luque

Beilstein J. Org. Chem. 2017, 13, 1982–1993, doi:10.3762/bjoc.13.194

• sources and iron precursors were applied to develop new bio-nanocomposites by mechanochemical milling processes. The proposed methodology was demonstrated to be advantageous in comparison with other protocols for the synthesis of iron oxide based nanostructures. Additionally, mechanochemistry has enormous

• in both the oxidation and alkylation reaction reveals a potential method for the valorization of lignocellulosic biomass. Keywords: alkylation; benzyl alcohol; benzyl chloride; iron oxide; mechanochemistry; microwave-assisted oxidation; polysaccharide; toluene; Introduction Heterogeneous catalysis

Solid-state mechanochemical ω-functionalization of poly(ethylene glycol)

• Michael Y. Malca,
• Pierre-Olivier Ferko,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2017, 13, 1963–1968, doi:10.3762/bjoc.13.191

• PEG with tosyl, bromide, thiol, carboxylic acid or amine functionalities in good to quantitative yields and with no polymer chain oligomerization, proving the versatility of the method. Keywords: amination; bromination; carboxylation; mechanochemistry; poly(ethylene glycol); solid state; thiolation

• of pharmaceutical industry for the development of cleaner, more efficient synthetic techniques [22], we now explore the possibility of accessing PEG derivatives in the solid-state. The use of mechanochemistry to achieve both supramolecular [23] and covalent [24] synthesis and modification of active

• synthesis of other mPEG derivatives by mechanochemistry, through ball-milling reaction with additional nucleophiles. The synthesis of terminally brominated mPEG (mPEG–Br) derivatives was achieved by milling of mPEG–OTs with LiBr (Scheme 1b). Analysis of the milled reaction mixture by 1H NMR revealed the