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

• in our previous work [29]. Milling experiments were performed using a commercially available vibratory ball mill (Pulverisette 23, Fritsch, Germany). For each experiment, stoichiometric quantities of reactants p-, m- and o- fluorobenzaldehyde (500 mg, ca. 4.03 mmol) and malonodinitrile (266.1 mg, ca

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

• showed that poly(ethylene oxide) end group modification is facile under ball-mill conditions [16]. Network polymeric material fabrications were also realized using ball milling [17][18][19]. As mentioned, many mechanochemical reactions realized exceptional efficiencies that solution synthesis cannot

• added. All reagents were placed in a 10 mL stainless-steel milling jar with three 7 mm diameter stainless-steel balls. The solid-state reaction mixture was placed into a high-speed vibration ball mill. After 30 min of high-speed vibration (30 Hz), 43% conversion was recorded, and PTMC with an Mn of 3930

• improvement of reaction efficiency. The high impact collision energy [28][29] and exothermic nature of the given ring-opening polymerization [30] could increase the temperature of a ball-mill system, which would speed up the polymerization rate [31][32]. To gain insight into thermal effects, we monitored the

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

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

• stabilities by exhibiting a decomposition temperature up to 320 °C. In 2013, Severin and co-workers reported the mechanochemical synthesis of large macrocycles with borasiloxane and imine links using a ball mill (Figure 12). In a polycondensation reaction using diamines, 4-formylbenzeneboronic acid and t

• -benzenetricarbonyl chloride and 1,4-phenylenediamine in a ball mill afforded 75% of the desired 2D polymer 24 within 15 min (Figure 13). When using 4,4'-diaminobiphenyl in place of 1,4-phenylenediamine the analogous 2D structure comprising biphenylene units was obtained within the same time albeit with a lower yield

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

• separation by column chromatography. A 5-fold scaled up version of the reaction using 3.37 mmol of 1 was carried out in a planetary ball mill (PBM) using 45 mL milling containers at 600 rpm, under otherwise identical conditions to afford product 2 in a similar yield. With TBDMS-protected glycidol 2 in our

• hands, a selective epoxide ring-opening reaction with fatty acids 3 leading to the formation of the corresponding sn-1,3-protected monoacylglycerols (MAGs 4) was attempted (Scheme 3). Initially, commonly used solution-based protocols were tested in the ball mill [33]. For example, 2 was reacted with

Synthesis of mono-functionalized S-diazocines via intramolecular Baeyer–Mills reactions

• Miriam Schehr,
• Daniel Hugenbusch,
• Tobias Moje,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2018, 14, 2799–2804, doi:10.3762/bjoc.14.257

• be reduced in a second synthetic step using lead in a ball mill. However, these reaction conditions are not suitable for functionalized S-diazocines due to poor yields and low reproducibility. Using halogenated precursors for the reductive azocoupling with lead a large amount of byproduct (details

• see Supporting Information File 1) is formed, which lowers the overall yield of S-diazocines 1–3 considerably. Further problems arise from the difficult separation of the azoxy compound from other byproducts. The yields of the azoxy reduction in the ball mill are varying between 18–46%. S-Diazocines

The mechanochemical synthesis of quinazolin-4(3H)-ones by controlling the reactivity of IBX

• Md Toufique Alam,
• Saikat Maiti and
• Prasenjit Mal

Beilstein J. Org. Chem. 2018, 14, 2396–2403, doi:10.3762/bjoc.14.216

• intramolecular control. At maximum contact of the reacting substances, i.e., under solvent-free mechanochemical conditions, 2-aminobenzamides, aryl-, alkylaldehydes and the iodine(V) reagent o-iodoxybenzoic acid (IBX) led to substituted quinazolin-4(3H)-one derivatives in fair yields. Keywords: ball-mill

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

• 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

• ] augments an earlier introduction describing both the parameters used to define such chemistry and also how this information is conveyed in synthetic schemes [16]. Stolle has written a comprehensive treatise on the chemical, technological and process parameters which influence the outcome of a ball mill

• commercially-available equipment which, for reactions of nucleosides and related materials has most commonly been the mixer ball mill (MBM – e.g., Figure 1a). Using a MBM, high energy collisions between reactants and one or more balls within a closed vessel (jar) are induced by vibrating the jar through a

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

• Katharina Hiebler,
• Georg J. Lichtenegger,
• Manuel C. Maier,
• Eun Sung Park,
• Renie Gonzales-Groom,
• Bernard P. Binks and
• Heidrun Gruber-Woelfler

Beilstein J. Org. Chem. 2018, 14, 648–658, doi:10.3762/bjoc.14.52

• Resch PM10 planet ball mill equipped with metal balls (d = 8 mm, 500 rpm, 10 min milling time) was used for dry milling of powdered Ce0.495Sn0.495Pd0.01O2–δ and wet milling (suspension in water) of Ce0.20Sn0.79Pd0.01O2–δ, respectively. These two catalysts were chosen since they showed the highest

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

• reaction time and provides a highly efficient methodology to realize the regioselective functionalization of acetanilides in yields up to 94% in a ball mill. Furthermore, the current methodology can be extended to the synthesis of ortho-brominated and ortho-chlorinated products in good yields by using the

• N-halosuccinimides. The influence of the milling frequency on the reaction of 1a with NIS. Palladium-catalyzed ortho-iodination of 1a in toluene. Plausible mechanism. Palladium-catalyzed ortho-bromination and chlorination of 1a in a ball mill. Optimization of the reaction conditions.a Substrate

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

• rapidly inspired other groups to follow this methodology. This has been proved by the work of Wenbing Yuan et al., in which a very important 3D BioMOF, known as HKUST-1, was synthesized by grinding together copper acetate with 1,3,5-benzenetricarboxylic acid (BTC, Figure 3) in a ball mill for 15 minutes

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

• different copper species for the solvent-free mechanochemical CuAAC in a ball mill, we conducted a number of milling experiments where we assayed catalytic action of most commonly used copper(0), copper(I) and copper(II) catalysts. Mechanochemical reactions were compared to traditional solvent-based

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

• ][24][25][27] to prepare the Pro–Pro dipeptide from the corresponding amino acid derivatives. We investigated the coupling of proline N-hydroxysuccinimide ester with proline methyl ester in a vibrating ball mill (vbm, Scheme 2) [23]. Surprisingly, while the coupling of various other amino acids

• trans-11 (racemic), which could be separated by crystallization or column chromatography [17][32][33]. Trying to avoid as much as possible the use of (toxic) solvents, we considered extending the known nucleophilic substitution in a ball mill [34][35][36][37][38][39][40][41] to this reaction system

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

• milling frequency on the course of a mechanochemical organic reaction conducted using a vibratory shaker (mixer) ball mill. The use of in situ Raman spectroscopy for real-time monitoring of the mechanochemical synthesis of a 2,3-diphenylquinoxaline derivative revealed a pronounced dependence of chemical

• is one of the fundamental parameters of mechanochemical reactions conducted by ball milling, and for a vibratory shaker (mixer) ball mill it represents the number of full oscillations of the milling vessel (milling jar) per unit time along a curved path (Scheme 2). It is often used as a simple

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

• impeller, and automated handling such as pumping and filtration. Since Lamaty and co-workers have shown in their seminal work that peptide synthesis could be performed in a ball-mill (BM) [9], various solvent-free or solvent-less peptide synthesis strategies have been developed [10][11][12][13][14][15][16

• peptide that inhibits Aβ42-induced neurotoxicity [21][22], and that is known to be difficult to produce due to high hydrophobicity and steric hindrance [23]. Results and Discussion Synthesis by using a ball-mill (BM) The Boc-VVIA-OBn tetrapeptide was first synthesized by using the ball-milling strategy

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

• commercial ball mill in the presence of stainless steel balls and air, and in the absence of solvent. The oxidation of solid 4-nitrobenzyl alcohol (1a) to 4-nitrobenzaldehyde (2a) was selected as a model reaction. Unfortunately, the alcohol-to-aldehyde conversion was very low (<15%), and the use of larger

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

• interactions such as hydrogen bonds, halogen bonds, and π∙∙∙π interactions [16][17][18][19]. For example, Toda et al. reported yields of 97% for Aldol condensations in the absence of any solvents [20]. Kaupp et al. described the first Knoevenagel condensation in a ball mill [21]. Compared to conventional

• -nitrobenzaldehyde (1) with malononitrile (2) using a ball mill. The stoichiometric reaction mixture was ball-milled for 60 minutes at 50 Hz in a conventional ball mill with either stainless steel or Perspex grinding jars. For both jar materials, the X-ray diffraction patterns of the product in comparison to those

• ball milling is needed for the completion of the reaction. The ball mill was stopped after 36 minutes and the reaction in the closed jar was monitored with Raman spectroscopy. The data show that under these conditions the reaction to the final product is completed within two hours. Consequently

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

• for the synthesis of the three catalysts Fe2O3-PS4, Fe2O3-PS4-MNP, and TiO2-Fe2O3-PS4. The three materials were synthesized using a 2:1 metal precursor/polysaccharide ratio (2 g of polysaccharide S4, 4 g of FeCl2·4H2O), in a ball mill (Retsch PM100 ball mill model), at 350 rpm for 30 min, using a 125

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

• ]. In this section some of the most important C–C bond forming reactions and their advantages are discussed. Aldol reaction In 2000, Raston and Scott first reported the aldol condensation reaction using veratraldehyde, 4-phenylcyclohexanone and 1-indanone in the presence of NaOH in a vibrating ball mill

• reacting catalyst. Su and co-workers reported an Fe(III)-catalyzed coupling of 3-benzyl indoles with molecules having active methylene group under solvent-free ball-mill in presence of silica gel as milling auxiliary. Using 10 mol % Fe(NO3)3·9H2O as catalyst and 1.0 equiv of DDQ afforded good yield of

• 2016 Juaristi and co-workers have reported Ugi 4-component reactions (4-CR) by liquid-assisted grinding (LAG) using MeOH. Equimolar amounts of benzaldehyde, chloroacetic acid, tert-butyl isocyanide, and propargylamine in the presence of 2 mol % InCl3, under ball-mill yielded the desired Ugi product in

Influence of the milling parameters on the nucleophilic substitution reaction of activated β-cyclodextrins

• László Jicsinszky,
• Kata Tuza,
• Giancarlo Cravotto,
• Andrea Porcheddu,
• Francesco Delogu and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 1893–1899, doi:10.3762/bjoc.13.184

• effect on the nucleophilic reaction. Keywords: cyclodextrins; milling parameters; nucleophilic substitution; planetary ball mill; Introduction Their hollow structures make cyclodextrins (CDs) a class of carbohydrates that can form inclusion complexes with organic molecules, inorganic salts and complex

• derivatization [8]. Although the preparation of carbohydrate-based complexes in a ball mill has been already reported [9][10][11], the use of mechanical activation for the chemical derivatization of CDs has been rather sporadic [12][13][14][15]. In this respect, it is worth noting that CDs exhibit a

• . The reaction was performed in a planetary ball mill and the processing parameters were systematically varied with the aim of pointing out their influence on the nucleophilic substitution reactions in terms of rate and yield. Specifically systematic variation involved rotation speed, milling tool

Solvent-free sonochemistry: Sonochemical organic synthesis in the absence of a liquid medium

• Deborah E. Crawford

Beilstein J. Org. Chem. 2017, 13, 1850–1856, doi:10.3762/bjoc.13.179

• . Keywords: mechanochemistry; organic; solvent-free; sonochemistry; synthesis; Introduction Mechanochemistry is typically regarded as the grinding of solid reagents in a ball mill (or mortar and pestle), to instigate and accelerate chemical reactions [1]. In recent years, mechanochemistry has evolved to

• carried out (where grinding results in degradation of the material). Finally, as with ball milling, there is potential for the scale-up of sonochemical reactions, therefore aiding in the drive towards sustainable chemistry. Typical laboratory employed planetary ball mill and ultrasonic bath. o-Vanillin in

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

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

• milling was performed at low temperatures (−30 °C) using an in-house ball mill equipped with a cooling jacket. As isothiocyanate component, liquid phenyl isothiocyanate and solid methyl, 1-naphthyl, 4-bromophenyl and 4-nitrophenyl isothiocyanates were screened. While ammonia, methylamine and dimethylamine

• absorption bands of N-(4-bromophenyl)thiourea (32d) at 1617 and 509 cm−1. Several other thiocarbamoyl benzotriazoles were also quantitatively transformed to primary thioureas by this method. For the purpose of performing the amination reaction in a ball mill, ammonia gas was generated in situ by milling the

Selective enzymatic esterification of lignin model compounds in the ball mill

• Ulla Weißbach,
• Saumya Dabral,
• Laure Konnert,
• Carsten Bolm and
• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1788–1795, doi:10.3762/bjoc.13.173

• Ulla Weissbach Saumya Dabral Laure Konnert Carsten Bolm Jose G. Hernandez Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany 10.3762/bjoc.13.173 Abstract A lipase-catalyzed esterification of lignin model compounds in the ball mill was developed combining

• out by ball milling, have recently attracted attention of a wider scientific community, owing to the many advantages the excellent mixing inside the ball mill can offer [1]. Besides avoiding or minimizing the use of organic solvents as reaction media, chemical transformations by ball milling very

• the ball mill (Scheme 1c). The results of this proof-of-concept study are presented here. Results and Discussion Due to the high complexity of the lignin structure, which often presents a challenge during the product composition analysis, the use of lignin model compounds to monitor preliminary

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

• . Reactions under solvent-free conditions in a ball mill gave good yields and could be put in place of the classical solution conditions. The method is general and can be applied to various imides and alkyl halides. Phthalimides prepared under ball milling conditions were used in a mechanochemical Gabriel

• employed. By conducting the reaction in a ball mill, solubility problems and the issues associated with the selection of the most suitable solvent could be avoided. In addition, solid-state reaction diminishes the heterogeneous character of alkylation, since inorganic bases in general are not soluble in

• ) Gabriel synthesis of amines was carried out in a ball mill. The synthetically desired development of a three-step, one-pot mechanochemical Gabriel synthesis of amines could not be accomplished, as the complex reaction mixtures containing considerable amounts of various side products such as bisamide 43

Encaging palladium(0) in layered double hydroxide: A sustainable catalyst for solvent-free and ligand-free Heck reaction in a ball mill

• Wei Shi,
• Jingbo Yu,
• Zhijiang Jiang,
• Qiaoling Shao and
• Weike Su

Beilstein J. Org. Chem. 2017, 13, 1661–1668, doi:10.3762/bjoc.13.160

• hybrid LDHs were then reduced by hydrazine hydrate (N2H4·H2O) to obtain the Pd catalyst supported on MgAl-LDHs (Pd/MgAl-LDHs). The as-prepared Pd/MgAl-LDH catalyst was further applied in representative cross-coupling Heck reactions under HSBM conditions (Scheme 1) by using a planetary ball mill

Mechanochemical borylation of aryldiazonium salts; merging light and ball milling

• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1463–1469, doi:10.3762/bjoc.13.144

• Jose G. Hernandez Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany 10.3762/bjoc.13.144 Abstract Merging of photo- and mechanochemical activation permitted studying the role of eosin Y in the borylation of aryldiazonium salts in a ball mill

• ball mill (Table 2). Control experiments by stirring/heating 1a–d and 2 in an oil bath until the melting of the mixture was reached, showed predominantly thermal decomposition of the aryldiazonium salts 1a–d into the 1-halo-4-fluorobenzene derivatives [23] and only in some cases trace quantities of 3a

• light on the role of the photocatalyst in the borylation of the aryldiazonium salts. Under non-catalyzed LAG/irradiation conditions, charge-transfer complexes between 1a and appropriate organic solvents could be responsible for the fast generation of the aryl cations in the ball mill, leading to the