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

• methanol was used to lubricate the molecular surface for an improved performance (known as liquid-assisted grinding, LAG) [42]. Unsymmetrical salens 1a‒h were obtained in the yield of 72% to 95% after being purified by column chromatography. Bromo-containing salen 1a was yielded the best (95%), presumably

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

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

• -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

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

• -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

Metal-free mechanochemical oxidations in Ertalyte^® jars

• Andrea Porcheddu,
• Francesco Delogu,
• Lidia De Luca,
• Claudia Fattuoni and
• Evelina Colacino

Beilstein J. Org. Chem. 2019, 15, 1786–1794, doi:10.3762/bjoc.15.172

• reactions of hydantoins [41][59]. However, also using this oxidant, we observed low conversions (31%) and the formation of significant amounts of byproducts, mainly halides and olefins (elimination byproducts). The use of liquid-assisted grinding (LAG) procedures [60][61][62] by adding small quantities of

Mechanochemical Friedel–Crafts acylations

• Mateja Đud,
• Anamarija Briš,
• Iva Jušinski,
• Davor Gracin and
• Davor Margetić

Beilstein J. Org. Chem. 2019, 15, 1313–1320, doi:10.3762/bjoc.15.130

• grinding additives to improve mass transfer and prevent pasting of the reaction mixture [26][27][28] (Table 1, entries 5–8) was detrimental to reaction yields. The addition of a small amount of solvents which was reported to facilitate several ball milling reactions (liquid assisted grinding, LAG) [29][30

Understanding the unexpected effect of frequency on the kinetics of a covalent reaction under ball-milling conditions

• Ana M. Belenguer,
• Adam A. L. Michalchuk,
• Giulio I. Lampronti and
• Jeremy K. M. Sanders

Beilstein J. Org. Chem. 2019, 15, 1226–1235, doi:10.3762/bjoc.15.120

• ). Alternatively, very small quantities of liquid can be added to the grinding mixture [5], a procedure known as "kneading" or "liquid-assisted grinding" (LAG) [4]. The liquid often accelerates reactions between solids or even enables new reactions [5][6][7]. Mechanochemical methods have been successfully applied

• kinetics is a relatively unexplored field, and we have explored only one reaction, but it seems likely that similar effects will operate for other reactions. Experimental The kinetic studies presented here were performed under ball-mill neat grinding (NG) and under ball mill liquid-assisted grinding (LAG

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

• , liquid-assisted grinding (LAG), the addition of a very small amount of a liquid, prevented chain-degradation from high impact collisions, and afforded PLA with over 100,000 g/mol. Thus, LAG was also tested in the PTMC synthesis [13][14] with toluene and THF as liquids. A catalytic amount of liquid (10 or

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

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

• acetic acid (for liquid-assisted grinding, LAG) led to the regioselective C–H activation (Figure 5) [58]. In 2008, the mechanochemical synthesis of both [2]- and [4]rotaxanes was reported by Chiu and co-workers. The reactions led to high yields of the products 12 and 13 under solvent-free conditions at a

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

• ). During subsequent discussions, liquid-assisted grinding (LAG) is used to describe only the latter case. The minimal level of solvent requirement is particularly advantageous in the context of charged nucleotide substrates as considerable cost, time and energy savings can be gained in the absence of

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

• used in liquid-assisted grinding (LAG) and properly chosen counter-ion pairing increases the percentage conversion of stilbenes in a mechanochemical Wittig reaction. Utilizing stepwise addition/evaporation of ethanol in liquid-assisted grinding also allows for the tuning of the diastereoselectivity in

• the ones obtained under traditional solution-based conditions. First, we observed that using functionalized resins allowed us to isolate the desired product in an easy and environmentally benign manner. Second, we observed that the incorporation of liquid-assisted grinding (LAG) increased the rate of

• . Conclusion Both a high dielectric constant of the solvent used in liquid-assisted grinding (LAG) and proper ion pairing were found to increase the percent conversion to stilbenes under mechanochemical conditions. Choosing appropriate ion pairs when LAG is utilized in the system also allowed tuning the

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

• ]. NG evolved into liquid-assisted grinding (LAG), also known as solvent-drop grinding or kneading, which includes the addition of catalytic amounts of solvent to facilitate the reaction. This technique proved to be useful for the synthesis of new compounds that could not be obtained by solution or NG

Main group mechanochemistry

• Agota A. Gečiauskaitė and
• Felipe García

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

• process is via the use of small amounts of liquid and/or solid additives, termed ion- and liquid-assisted (ILAG) or liquid-assisted grinding (LAG), respectively [34][35]. These techniques, in contrast to “dry” milling, often offer advantages such as shorter reaction times and/or greater product

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

• yielded the best results with both molecular weight (Mw) mPEGs. NaOH is a strong base, thus favoring deprotonation of mPEG over weaker bases to facilitate subsequent tosylation. The deprotonation step (Scheme 1a) also generates water locally, which may have led to liquid-assisted grinding (LAG) conditions

One-pot multistep mechanochemical synthesis of fluorinated pyrazolones

• Joseph L. Howard,
• William Nicholson,
• Yerbol Sagatov and
• Duncan L. Browne

Beilstein J. Org. Chem. 2017, 13, 1950–1956, doi:10.3762/bjoc.13.189

• a paste that does not mix well and results in low reaction conversions. Clearly the presence of such a material may have a knock-on effect on any multistep process. Liquid-assisted grinding (LAG) is another phenomenon that can provide enhancement to the reaction outcome and again should be

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

• of their low reactivity. Recently, Li and Su with co-workers have developed a liquid-assisted grinding (LAG) method for the Suzuki–Miyaura coupling between aryl chlorides and boronic acids to synthesize the biaryls in nearly quantitative yield. Under optimized conditions 2 mol % Pd(OAc)2 and 4 mol

• 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

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, 1728–1734, doi:10.3762/bjoc.13.167

• . Several chiral organocatalysts and even enzymes have proved to be resistant to milling conditions, which allows for rather efficient enantioselective transformations under ball-milling conditions. The present article reports the first example of a liquid-assisted grinding (LAG) mechanochemical enzymatic

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

• underexplored [14], despite photocatalysis could clearly benefit from the excellent mixing under neat or liquid-assisted grinding (LAG) [15] conditions. Additionally, in contrast to solution-based methods, reactions by milling do not suffer from solubility restrictions due to the possibility to bring reactants

Nucleophilic displacement reactions of 5′-derivatised nucleosides in a vibration ball mill

• Olga Eguaogie,
• Patrick F. Conlon,
• Francesco Ravalico,
• Jamie S. T. Sweet,
• Thomas B. Elder,
• Louis P. Conway,
• Marc E. Lennon,
• David R. W. Hodgson and
• Joseph S. Vyle

Beilstein J. Org. Chem. 2017, 13, 87–92, doi:10.3762/bjoc.13.11

• ) remained untransformed during (dry) VBM or liquid-assisted grinding (LAG) in the presence of DMF with excess KSeCN (3 equiv). As found previously, the addition of catalytic TBAI (vide supra) did not alter this outcome nor did the use of a larger excess (5 equiv) of selenocyanate. The addition of DMF to the

• -methoxybenzylthiolate salts used to optimise VBM conditions. Thiolate displacement reactions of 5′-derivatised nucleosides using VBM. Selenocyanate displacement reactions of 5′-derivatised nucleosides using liquid-assisted grinding (LAG) or VBM. Optimisation of VBM conditions for the reaction of 5′-chloro-5

Extrusion – back to the future: Using an established technique to reform automated chemical synthesis

• Deborah E. Crawford

Beilstein J. Org. Chem. 2017, 13, 65–75, doi:10.3762/bjoc.13.9

• formation In 2009, Alvarez-Nunez et al. of Amgen used TSE to scale up the synthesis of a cocrystal which had already been reported to be synthesised successfully by ball milling (employing liquid-assisted grinding (LAG)). This was the first example demonstrating that mechanochemical synthesis could be

Poly(ethylene glycol)s as grinding additives in the mechanochemical preparation of highly functionalized 3,5-disubstituted hydantoins

• Andrea Mascitti,
• Massimiliano Lupacchini,
• Ruben Guerra,
• Ilya Taydakov,
• Lucia Tonucci,
• Nicola d’Alessandro,
• Frederic Lamaty,
• Jean Martinez and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 19–25, doi:10.3762/bjoc.13.3

• investigated in the presence of various poly(ethylene) glycols (PEGs), as safe grinding assisting agents (liquid-assisted grinding, LAG). A comparative study under dry-grinding conditions was also performed. The results showed that the cyclization reaction was influenced by the amount of the PEG grinding

• agents. In general, cleaner reaction profiles were observed in the presence of PEGs, compared to dry-grinding procedures. Keywords: ball-milling; 1,1’-carbonyldiimidazole (CDI); hydantoins; mechanochemistry; liquid-assisted grinding (LAG); poly(ethylene) glycols (PEGs); Introduction Poly(ethylene

Mechanochemistry assisted asymmetric organocatalysis: A sustainable approach

• Pankaj Chauhan and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2012, 8, 2132–2141, doi:10.3762/bjoc.8.240

• grinding and liquid-assisted grinding (LAG) have been applied to the synthesis of mono- and bis(thiourea)s in quantitative yield by using the click coupling of aromatic or aliphatic diamines with aromatic isothiocyanates (Scheme 9) [54]. The mechanochemically prepared chiral molecules were applied as