Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• examples described below, minimal amounts of solvent are used to homogenize the reaction mixture. This approach is called liquid-assisted grinding (LAG) and it is commonly accepted as a mechanochemical approach [58].. Throughout the text, we adopted the term photomechanochemistry to include both

• improve the result. However, the addition of a LAG agent (MeOH, 50 μL) in the automated grinding step dramatically improved the outcome (quantitative conversion after 20 h of irradiation). Intriguingly, the simultaneous LAVG and irradiation enabled the formation of 5.3 in 97% yield upon reduced

• are crucial for product formation. Lastly, the author noted that the inclusion of acetonitrile as a LAG agent enabled the transformation even without the presence of a photocatalyst [72][74]. In 2023, Braunschweig and co-workers reported the photomechanochemical [2 + 2] cycloaddition of acenaphthylene

Investigation of a bimetallic terbium(III)/copper(II) chemosensor for the detection of aqueous hydrogen sulfide

• Parvathy Mini,
• Michael R. Grace,
• Genevieve H. Dennison and
• Kellie L. Tuck

Beilstein J. Org. Chem. 2024, 20, 2818–2826, doi:10.3762/bjoc.20.237

• ·3Cu]3+, 10 mM HEPES buffer (pH 7.4) resulted in a sigmoidal growth curve, with a “lag phase” (Figure 3). This was an unexpected result as a linear increase in luminescence regain was anticipated on addition of HS−(aq) ions to the solution. We interpret this “lag phase” as a consequence of Cu2+ ions

• concentration range of 0–15 μM (R2 = 0.974, Figure 4). The linear increase in luminescence, compared to the “lag-phase” observed in HEPES buffer, can be attributed to the Tris-HCl buffer forming a complex with Cu2+ ions, a phenomenon only weakly observed with HEPES buffer [19][20]. We hypothesize that using

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

• 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

Understanding X-ray-induced isomerisation in photoswitchable surfactant assemblies

• Beatrice E. Jones,
• Camille Blayo,
• Jake L. Greenfield,
• Matthew J. Fuchter,
• Nathan Cowieson and
• Rachel C. Evans

Beilstein J. Org. Chem. 2024, 20, 2005–2015, doi:10.3762/bjoc.20.176

• . It should be noted that a lag between the time taken to reach the PSS and the time for the new micelle morphology to form is expected. This is due to the additional time that is required for diffusion and reassembly of the AzoTAB in the Z conformation into the new equilibrium structure [22]. The

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

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• Information File 1). At 0.5 M, only 63% of EtOx were converted after 24 h. Interestingly, no significant peaks indicating PEtOx formation were detected in the 1H NMR spectra during the first 3.0 h of incubation, suggesting a lag time. The SEC traces remain mostly monomodal with a narrow molar mass

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

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

• incomplete and a mixture containing some starting material (1a), two other spots which are identified as o-monobromo (2a) as major (57%), and o-dibrominated p-cresol (3a) as minor (20%) constituents, was obtained (Table 1, entry 1). Next, the reaction mixture was ground under LAG conditions with ethanol and

• an improved yield (77%) of the monobromo product 2a, with a reduced amount of 3a (12%), and a nominal recovery of the starting material were observed (Table 1, entry 2). Incomplete consumption of starting phenol 1a was primarily due to over bromination. The LAG in the presence of water afforded

• selected as the LAG agent keeping all other parameters the same. Interestingly, the monobrominated product 2a was obtained almost exclusively in an excellent yield (91%) within just 5 min of grinding (Table 1, entry 6). The attempted model reaction under solid-state grinding using silica gel was sluggish

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

• facilitated by the Zn/Cu couple [23]. When LAG THF reactions were carried out without anthracene, 15 was major product, whereas 16 is the major product in LAG MeOH milling (Supporting Information File 1, Table S1). Scope of the reaction With the optimized conditions established, the scope of the reaction and

• LAG, milling again gave 22, but it was accompanied with a larger amount of 40 and some side-product 12. A control LAG milling experiment without furan led to 40 and a significant amount of 12. These experiments emphasize the complementarity of ball milling conditions with solution chemistry (in

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

• dynamics of the formation of cyclopalladated intermediates In-I, LAG reactions of Pd(OAc)2 with L6–8 and TsOH were performed using 25 µL of MeCN as a liquid additive in a molar ratio of 1:1:1 (Ln/Pd(OAc)2/TsOH). In situ Raman monitoring of C–H bond activation was possible for L6 and L7, while in the case

• azobenzenes is strongly influenced by the nature of the azobenzene substituents. Conclusion We have applied a mechanochemical protocol for the halogenation of 4,4’-functionalized azobenzenes in a ball mill under NG or LAG conditions, using NXS (X = Cl, Br, and I) as the halogen source. Halogenation of

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• O1); a small oligomer that forms transiently during the early stages of the lag phase (oligomer O2) and 4 spectroscopically distinct forms of oligomers that appear during the later stages of aggregation and apparently coexist with the proto-fibrillar species (oligomers O3–O6, Figure 10). It is worth

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

Opening up connectivity between documents, structures and bioactivity

• Christopher Southan

Beilstein J. Org. Chem. 2020, 16, 596–606, doi:10.3762/bjoc.16.54

• associated with their D-C mappings. The first is that in their SID records they index DOIs in the Depositor Comments but not PMIDs. This means there is no connection into the Entrez system (although this may have been an expedient choice to avoid the lag time associated with post-publication PMID assignments

Naphthalene diimides with improved solubility for visible light photoredox catalysis

• Barbara Reiß and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 2043–2051, doi:10.3762/bjoc.15.201

• nm and 638 nm LEDs do overlay better but show lower yields of 55% and 62%, respectively, in photoredox catalysis. The lag phases of more than 30 min in the latter experiments indicate that indeed the enamine formation plays a crucial role. According to the mechanism suggested by Yoon et al. the

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

• ][39][40][41][42][43]. Hence, before one can develop elementary kinetic equations for these processes, it is crucial to understand the types of processes that must be independently considered. Recently, we have been investigating the final reaction equilibrium achieved under ball-mill LAG conditions

• the progress of product formation as a function of grinding time. Purposely designed stability experiments of the ball mill NG and LAG reactions were conducted by interrupting the milling experiments of 1-1 + 2-2 + DBU at different times and storing the grinding jars sealed. After several months and

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

• polymer with surface areas of up to 1720 m2g−1 and pore volumes of up to 1.55 cm3g−1. The application of LAG (liquid-assisted grinding) revealed a profound impact of the liquid´s boiling point on the textural properties of the obtained polymer materials. Finally, the materials are characterized by vapour

• maximum pressure to 0.42 bar (Figure 3B). Influence of the LAG additive Interestingly, besides decreasing the vessel pressure, this 1 mL of solvent also affected the textural properties of the polymer positively. Consequently, we went on to investigate the influence of the LAG reagent by changing the

• 0.67 and 0.97 nm micropores for LAG-HCP (Figures S5 and S6 in Supporting Information File 1). In addition, the amount of mesopores in the sample is also slightly higher for the LAG sample. The solubility of the released gas inside the liquid seems to play a minor role since good results can be obtained

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

• 20 µL to 100 mg TMC), however, failed to protect the poly(trimethylene carbonate) chain from mechanical degradation and similar molecular weights were obtained, regardless of LAG. The LAG for mechanochemical polymerization reactions has been studied only in limited cases so far and the exact working

• mechanism is currently obscure. To have a better understanding of LAG on chain protection, extensive studies are currently in progress. Conclusion A mechanochemical method, ball milling, was applied to the synthesis of poly(trimethylene carbonate). The representative organocatalyst, DBU, exhibited excellent

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

• 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 and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• Escherichia coli reporter system [9]), an intriguing effect upon the growth of E. coli and Staphylococcus aureus was noted, which showed an extended lag phase in response to the compounds (except 4, which was inactive towards E. coli. It should be noted that in this previous publication, the graphical data

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

• copper salts was found. In an attempt to expedite the LAG reaction, millimol-scale reactions between the p-azobenzene-appended alkyne and 5′-azido-5′-deoxythymidine were attempted in a more capacious copper vessel with a 15 mm diameter zirconia ball (Figure 3). Clean and complete click reactions were

• using LAG (Scheme 9) [45]. Yields were slightly enhanced following presilylation of the bases in solution prior to ball milling and under these conditions, the corresponding protected 6-chloropurine riboside could also be accessed. Multiple products were formed from N2-iso-butyrylguanine and

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 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

• 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

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• group. Either of these steps can be rate-limiting, and we have encountered two-step kinetics with a lag-phase in some reactions involving aminoterminal primers [27]. More often, though, and in all cases involving ribonucleosides at the 3'-terminus of the primer, kinetics characteristic of a single rate

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• fibrillization assay was performed using thioflavin-T (ThT) fluorescence spectroscopy [14][15][39][40][41][42]. The fluorescence curve of the control peptide (Aβ1-42 10 µM, purple curve, Figure S26, Supporting Information File 1) displayed a typical sigmoid pattern with a lag phase corresponding to the