RSC Mechanochemistry最新文献

{"title":"From ball-milling to bead-milling technology: rapid optimization and scale-up of a one-pot Wittig olefination-Diels-Alder reaction sequence using an agitator bead mill.","authors":"Nina Biedermann, Johanna Templ, Kenneth Banderob, Philippe M C Roth, Michael Schnürch","doi":"10.1039/d6mr00016a","DOIUrl":"10.1039/d6mr00016a","url":null,"abstract":"<p><p>Mechanochemical methods offer a sustainable alternative to traditional solution-based synthesis, yet their scalability beyond laboratory-scale ball mills remains a challenge and often requires lengthy re-optimization for larger scales. Herein, we report the rapid batch translation of a one-pot Wittig olefination-Diels-Alder reaction sequence from a ball mill to an agitator bead mill (DYNO®-MILL RESEARCH LAB), achieving a scale-up from milligram to multi-gram quantities. Crucially, this translation was accomplished with minimal on-the-fly optimization, requiring only a few bead-milling runs to identify suitable operating conditions and perform the transformation in batch mode with good efficiency. Our results provide a practical case study for the scalability of mechanochemical reactions by using bead-milling technology and highlight the potential of bead-milling devices for future process development.</p>","PeriodicalId":101140,"journal":{"name":"RSC Mechanochemistry","volume":" ","pages":"768-773"},"PeriodicalIF":3.3,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13359023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148440687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying new solid forms of a labile pharmaceutical compound by additive assisted mechanochemistry.","authors":"Azhidhack Hadjipour, Nutifafa Yao Crown, Gayatri Gayatri, Oisín N Kavanagh","doi":"10.1039/d6mr00025h","DOIUrl":"10.1039/d6mr00025h","url":null,"abstract":"<p><p>Mechanochemical processing of labile active pharmaceutical ingredients (APIs) presents a fundamental trade-off: added solvent can accelerate solid form transformations yet may simultaneously promote chemical degradation. This study aims to explore this tension with an oxidation prone model pharmaceutical, cysteamine. Specifically, we examine the effects and interactions of antioxidant incorporation, reactant stoichiometry, ball to powder ratio (BPR), milling duration, and solvent assisted grinding on solid form screening success rates and yield. We find that the incorporation of ascorbic acid (ASC) as an antioxidant markedly improved resistance to oxidative degradation under a large set of milling conditions. Systematic variation of ASC molar ratios revealed an optimal composition at 1 : 1 : 2 (cysteamine : coformer : ASC) which reproducibly improved cysteamine recovery (90-110%, <i>n</i> = 3) and promoted the formation of a new crystalline phase, verified by PXRD. However, increasing the ASC ratio beyond 1 : 1 : 5 led to diminished product quality, indicating a threshold beyond which performance declines. These findings establish practical design insights for solid-form screening of chemically fragile pharmaceuticals.</p>","PeriodicalId":101140,"journal":{"name":"RSC Mechanochemistry","volume":"3 5","pages":"661-667"},"PeriodicalIF":3.3,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Moving mechanochemistry forward: mechanochemistry and organometallic synthesis","authors":"Dillon Button-Jennings and Timothy P. Hanusa","doi":"10.1039/D6MR90009G","DOIUrl":"https://doi.org/10.1039/D6MR90009G","url":null,"abstract":"<p >A graphical abstract is available for this content</p>","PeriodicalId":101140,"journal":{"name":"RSC Mechanochemistry","volume":" 3","pages":" 327-329"},"PeriodicalIF":0.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/mr/d6mr90009g?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147872263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ball-milling synthesis of α-bromoacrylates from solvent-free in situ prepared ethyl diethylbromophosphonate","authors":"Marie Caldiero, Jean-Philippe Bouillon and Thomas Castanheiro","doi":"10.1039/D6MR00029K","DOIUrl":"https://doi.org/10.1039/D6MR00029K","url":null,"abstract":"<p >A mechanosynthesis of α-bromoacrylates was described from commercially available triethyl phosphonoacetate by using a ball-milling-assisted bromination/HWE one-pot process. Initially, the bromination and the HWE protocols were independently optimized under mechanochemical conditions using a weak base and short reaction time. The solvent-free one-pot procedure required neither sequential addition nor an excess of reagents, thereby minimizing synthetic waste. α-Bromoacrylates were obtained with a general high efficiency, either through the solvent-free HWE (36 examples, from 26 to 98% yields) or <em>via</em> the one-pot procedure (9 examples, from 27 to 91% yields), with moderate <em>Z</em>-selectivity. This practical synthetic methodology was further extended to the synthesis of α-iodo- and α-chloroacrylates using NIS and NCS as iodinating and chlorinating agents, broadening the scope of halogenated alkenes formation through our one-pot approach. The α-bromoacrylates were then reacted in a ball-milling-assisted Ullman coupling, demonstrating the synthetic utility of the solvent-free synthesized products.</p>","PeriodicalId":101140,"journal":{"name":"RSC Mechanochemistry","volume":" 3","pages":" 459-465"},"PeriodicalIF":0.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/mr/d6mr00029k?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147872190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanosynthesis of cocrystals and coamorphous binary drug–drug systems with apremilast core: structural and biological studies†","authors":"K. Trzeciak, R. Dolot, M. K. Dudek, E. Wielgus, S. Kazmierski, P. Paluch, J. Czernek, J. Brus, K. Wiktorska, I. Wadas, K. Głowacka, A. Lange and M. J. Potrzebowski","doi":"10.1039/D6MR00014B","DOIUrl":"https://doi.org/10.1039/D6MR00014B","url":null,"abstract":"<p >In this paper, we discuss an issue important for understanding the mechanism of forming pharmaceutical binary systems and their safety in specific therapies. The main aim of this article is to answer the question of whether, in mechanochemical processes, the crystallographic form of the starting substances (substrates) affects the course of the reaction and the nature of the products obtained. Two crystallographic forms of the apremilast (APR), which is a drug used in the treatment of psoriasis and psoriatic arthritis, were utilized. As co-formers, medicines from the nonsteroidal anti-inflammatory drug (NSAID) group were used, including salicylic acid (SA), ethenzamide (ET), and paracetamol (PA) which is classified as an analgesic antipyretic drug (AAD). Each of them has a well-defined crystal structure determined by X-ray diffraction. During the course of the studies, it was found that ball milling of the physical mixture produces cocrystals of APR:SA and APR:ET, whereas APR:PA does not. The difference in reactivity is discussed in the context of the preorganization mechanism and the propensity to disrupt the dimeric structure present in the crystal lattice. The disruption of dimers in the ball mill allows the formation of isolated molecules (SA, ET), which complement the cocrystal structure by positioning themselves in the aromatic pocket of APR. Such a process is not observed in the case of PA. For testing the biological properties of new products, we selected the APR:ET cocrystal as a representative sample. Importantly, biological studies showed that the resulting binary system is cytotoxically safe and does not exhibit any undesirable effects.</p>","PeriodicalId":101140,"journal":{"name":"RSC Mechanochemistry","volume":" 3","pages":" 444-458"},"PeriodicalIF":0.0,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/mr/d6mr00014b?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147872182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimisation of the mechanochemical synthesis time of thermoelectric material Mg3Sb2–Mg3Bi2","authors":"Alena Mikhailova, Aleksandr Markin, Kseniia Shcherbakova, Yurii Kuznetsov, Vlad Dybov and Natalia Tabachkova","doi":"10.1039/D5MR00149H","DOIUrl":"https://doi.org/10.1039/D5MR00149H","url":null,"abstract":"<p >The present paper sets out the optimisation of the mechanochemical synthesis process of the thermoelectric material Mg<small>_3.2</small>Sb<small>_1.5</small>Bi<small>_0.45</small>Te<small>_0.05</small>. The current study investigates the effect of varying the time in the range from 1 to 9 hours on the phase composition, morphology of powders and thermoelectric properties of the samples obtained. It was established that the formation of the α-phase is complete after a period of 5 hours of mechanochemical synthesis. It was determined through the utilisation of scanning electron microscopy, in conjunction with an image analysis algorithm written in Python, that by 5 hours, a median particle size of 3.7 µm and the most uniform size distribution are achieved. It has been demonstrated that an increase in the duration to 7–9 hours results in particle agglomeration without any alteration to the phase composition. It was established that the specimen extracted from the powder following a period of 5 hours of mechanochemical synthesis possesses a thermoelectric figure of merit of <em>zT</em> ≈ 0.92 at 765 K. This investigation enabled the determination of the optimal time for the mechanochemical synthesis of the thermoelectric material Mg<small>_3.2</small>Sb<small>_1.5</small>Bi<small>_0.45</small>Te<small>_0.05</small> through the utilisation of computer vision methodologies.</p>","PeriodicalId":101140,"journal":{"name":"RSC Mechanochemistry","volume":" 3","pages":" 402-409"},"PeriodicalIF":0.0,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/mr/d5mr00149h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147872270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aerobic mechanochemical RAFT copolymerization of thioctic acid with solid monomers","authors":"Xiaoyang Shao, Haoyang Feng, Wenjing Liu, Xiaoyu Wang, Chen Wang, Jinhong Han and Zhenhua Wang","doi":"10.1039/D5MR00163C","DOIUrl":"https://doi.org/10.1039/D5MR00163C","url":null,"abstract":"<p >Mechanochemical solid-state radical polymerization still faces significant challenges, primarily due to limited mass transfer and inefficient initiation mechanisms under these conditions. This study proposes a robust mechanochemical approach for preparing biodegradable vinyl copolymers, enabling solvent-free RAFT copolymerization of thioctic acid (TA) with various solid-state monomers—including acrylamide derivatives and styrene derivatives—under aerobic conditions. By utilizing mechanical-to-chemical energy transduction, we achieved programmed dissociation of amine-coordinated alkylborane initiators, thereby enabling precise control over radical generation within a heterogeneous solid matrix. Under optimized ball-milling conditions at 30 Hz, copolymers of <em>N</em>-isopropylacrylamide (NiPam) and TA were synthesized with high conversions (up to 81.0%) and narrow dispersities (<em>Đ</em> &lt; 1.61). The system also exhibited broad compatibility with styrenic monomers such as vinylbenzoic acid (VBA), yielding well-defined copolymers. Systematic studies revealed that the coordination strength of the initiator and the structural compatibility of the chain transfer agent (CTA) play critical roles in regulating polymerization kinetics. This work establishes a versatile mechanistic framework for the design of dynamic covalent materials <em>via</em> sustainable, solvent-free mechanochemical pathways.</p>","PeriodicalId":101140,"journal":{"name":"RSC Mechanochemistry","volume":" 3","pages":" 421-428"},"PeriodicalIF":0.0,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/mr/d5mr00163c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147872180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sign of mechanochemical curvature governing O2 activation mechanisms and reactivity on rippled supports","authors":"Sayan Banerjee","doi":"10.1039/D5MR00147A","DOIUrl":"https://doi.org/10.1039/D5MR00147A","url":null,"abstract":"<p >Two-dimensional (2D) materials are inherently prone to forming ripples and wrinkles that create regions of nonzero curvature – a mechanochemical landscape arising from intrinsic deformation – thereby modulating their electronic structure and a range of associated properties. Such curvature effects have implications for stability, quantum processes, and adsorption phenomena. The influence of curvature—treated as a vector descriptor distinguishing positive and negative curvature—on reactivity remains underexplored, particularly in the context of small-molecule activation and multistep catalytic reactions. Here, we investigate rippled N-doped graphene and quantify how curvature, viewed as a local mechanochemical deformation, modulates O<small>₂</small> reactivity on single-atom sites, denoted as M–N–C (M = Fe, Co, Mn, Pt), using density functional theory. We find that the sign of curvature determines the O<small>₂</small> activation mode: for Mn and Fe, negatively curved regions (mountain-shaped) favor an <em>η</em><small>²</small> side-on configuration, whereas positively curved regions (valley-shaped) promote an <em>η</em><small>¹</small> end-on mode. In contrast, Co and Pt exhibit only curvature-independent <em>η</em><small>¹</small> binding. The <em>η</em><small>²</small> mode observed for Fe and Mn resembles molecular O<small>₂</small> adducts in transition-metal complexes. Curvature-dependent charge transfer enhances electron donation at negatively curved sites, facilitating O<small>₂</small> activation. We establish curvature-resolved scaling relations for oxygen reduction reaction (ORR) intermediates (OOH, O, and OH), highlighting where the global linear relationships remain valid and where they break down when curvature is introduced as a geometric variable. The sign of curvature also modulates ORR overpotentials: positive curvature regions yield lower overpotentials, whereas negative curvature sites lead to higher values for Fe and Mn. Consequently, we predict that negatively curved, mountain-like sites can be engineered for O-atom transfer reactions to organic substrates, which compete with ORR under electrochemical conditions. Finally, we show that variable curvature further influences the overpotential by enabling different ORR steps at varying curvatures on a corrugated surface. Overall, curvature can be harnessed to enable distinct reactivity from identical catalytic motifs, underscoring the importance of incorporating dynamic curvature effects in future theoretical and experimental studies.</p>","PeriodicalId":101140,"journal":{"name":"RSC Mechanochemistry","volume":" 3","pages":" 410-420"},"PeriodicalIF":0.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/mr/d5mr00147a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147872179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sono-mechanical activation-assisted proton-catalyzed self-polymerization of AMPS in water: hydrogel formation and its application as a functional additive in ordinary Portland cement","authors":"Kuldeep Rajpurohit, Sabrina A. Shaikh, Ashok K. Pandey and Hemlata K. Bagla","doi":"10.1039/D5MR00122F","DOIUrl":"https://doi.org/10.1039/D5MR00122F","url":null,"abstract":"<p >A green, initiator-free method for polymerizing 2-acrylamido-2-methyl-1-propane sulfonic acid (AMPS) was developed using low-frequency ultrasound (20 ± 3 kHz) in aqueous solution. Unlike conventional sonochemistry, where radical formation occurs <em>via</em> water sonolysis, the radical generation originates directly from the AMPS monomer, as verified by ESR, DPPH radical scavenging assays and NMR experiments. ESR experiments indicated the radical formation on AMPS at elevated temperatures, which was lowered by cavitation-induced shear forces caused by low-frequency ultrasound. Water functions as a medium for proton-assisted activation, as no polymerization occurs in aprotic solvents, such as DMF and 1-decanol, as well as a hydrogen-bonded deep eutectic solvent (choline chloride : ethylene glycol in a 1 : 2 mol proportion). Comparative experiments showed that acrylamide, methacrylic acid, and (3-acrylamidopropyl)trimethylammonium chloride failed to polymerize ultrasonically, underscoring the unique reactivity of AMPS. AMPS also polymerized under microwave heating, albeit at a higher temperature, further confirming that cavitation-induced mechanical activation assists but does not solely govern radical formation. Mechanistic validation was obtained through model reactions involving acrylamide polymerization in the presence of methane sulfonic acid (1 : 1 mol ratio), and AMPS did not polymerize in its neutralized Na<small>⁺</small> form. These results establish that the sulfonic acid group serves dual functions, as a proton donor and as a charge-balancing counterion, thereby enabling an acid-assisted, hydrogen-bond-directed radical polymerization pathway under sono-mechanical activation. The poly(AMPS) hydrogels were characterized by FESEM, thermal analysis and swelling experiments. The tunable swelling behavior, governed by the crosslinker density, was observed with water uptake decreasing from 1678 wt% at 2 mol% MBA to 250 wt% at 15 mol%. Lightly crosslinked gels exhibited self-healing behavior driven by reversible hydrogen bonding. GPC and viscosity analyses revealed simultaneous cavitation-induced depolymerization and radical polymerization, similar to ionizing radiation-based polymerization, though rapid crosslinking stabilized the hydrogel network. The incorporation of functional polymeric hydrogels into cementitious systems has emerged as an effective strategy for modifying hydration behavior, mechanical performance, and microstructural development. The cross-linked poly(AMPS) hydrogel was used in its calcium form (Ca-poly(AMPS)) as an additive in ordinary Portland cement, and its effect was evaluated as functions of setting time, compressive strength, tensile strength, and heat of hydration.</p>","PeriodicalId":101140,"journal":{"name":"RSC Mechanochemistry","volume":" 3","pages":" 429-443"},"PeriodicalIF":0.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/mr/d5mr00122f?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147872181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanochemical base-catalyzed isomerization and deuteration of allylbenzenes","authors":"Ruoxuan Liu, Xiaochun He, Ruiling Qu, Chengcheng Li, Xiaohong Wang, Xuemei Zhang and Zhong Lian","doi":"10.1039/D5MR00126A","DOIUrl":"https://doi.org/10.1039/D5MR00126A","url":null,"abstract":"<p >Trideuteromethylation has gained significant importance in modern drug development for its ability to fine-tune pharmacokinetic properties and enhance metabolic stability through the deuterium kinetic isotope effect. Currently, most methods for alkene double-bond migration (<em>e.g.</em>, transition-metal catalysis) suffer from drawbacks such as substantial waste generation, high reaction temperatures, and extended reaction durations. Herein, we report a universal mechanochemical strategy for the rapid and metal-free isomerization and deuteration of allylbenzenes. Utilizing only catalytic KO<em>t</em>Bu and stoichiometric DMSO-<em>d</em><small>₆</small>, this method enables precise CD<small>₃</small> incorporation within 15 minutes under ambient conditions. The protocol exhibits broad functional group tolerance, is scalable, and applicable to late-stage deuteration of natural products, offering a practical and sustainable approach to deuterated pharmaceuticals. In addition, mechanistic studies indicate that the H/D exchange catalyzed by KO<em>t</em>Bu is a radical process.</p>","PeriodicalId":101140,"journal":{"name":"RSC Mechanochemistry","volume":" 3","pages":" 338-344"},"PeriodicalIF":0.0,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/mr/d5mr00126a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147872265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}