High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• are one of the major driving forces in green synthesis [1][2]. High hydrostatic pressure (HHP) activation, one of such methods, is based on mechanical compression force. The typical pressure range is 2–20 kbar that is orders of magnitude greater than the conditions traditionally employed in chemistry

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• ], medicine [3], sensing [4] and energy storage [5]. Typically, bulk graphene is obtained using a top-down approach, where graphite is exfoliated using chemical or mechanical methods [6][7]. However, this method does not provide precise control over the structure of graphene and graphenoid materials, which is

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

• Sustainability, University of Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy 10.3762/bjoc.21.33 Abstract Photomechanochemistry, i.e., the merger of light energy and mechanical forces, is emerging as a new trend in organic synthesis, enabling unique reactivities of fleeting excited states under solvent

• -minimized conditions. Despite its transformative potential, the field faces significant technological challenges that must be addressed to unlock its full capabilities. In this Perspective, we analyze selected examples to showcase the available technologies to combine light and mechanical forces, including

• developed, where additional energy is applied to increase mixing such as pulsation [26][27][28], ultrasound energy [29], segmented flow [30], or mechanical stirring [31]. In line with the recent emphasis on Green Chemistry principles [32][33], alternatives have been developed in order to reduce the amount

Quantifying the ability of the CF₂H group as a hydrogen bond donor

• Matthew E. Paolella,
• Daniel S. Honeycutt,
• Bradley M. Lipka,
• Jacob M. Goldberg and
• Fang Wang

Beilstein J. Org. Chem. 2025, 21, 189–199, doi:10.3762/bjoc.21.11

• . We expect this information to be useful for the rational application of the CF2H group in drug development and molecular design. Previous quantum mechanical calculations revealed that the CF2H···O binding energy (ΔE) ranges from 1.0 kcal/mol to 5.5 kcal/mol [14][15][18][21]. In addition, as measured

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• membranes. In this example by Buscema et al. it was observed that liposome vesicles can deform under mechanical stress to yield similar structures as the PSar-PBLG vesicles [32]. It was attempted to change the shape of the assembled vesicles following a similar method as previously developed for PEG-PS

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• cross-linking of the hydroxy groups on CDs could extend the molecular/material design. As the di-isocyanate macromonomer was used for long axle components, the coverage ratio of CDs in this system was 3–5%, which was significantly lower than those of other systems in 2020. The mechanical properties of

• different from that of a single CD molecule. Such an aggregation behavior of polyrotaxane induces the increase of the mechanical strength of the material or the construction of a nanosheet, which is beneficial for material application. Meanwhile, CD-based polyrotaxane requires various synthetic demands, as

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

• absorption of mechanical energy and they are influenced by several factors, including the lack of solvation, changes in morphology and rheology of the reaction mixtures during the milling, and variations in concentration and dielectric environment. Consequently, an increased reactivity can be achieved

Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

• attached to the molecules themselves or is interacting with them. Introducing fluorescent dyes to self-assembling systems affects their chemical and mechanical stability as the hydrophobic features can destabilise the self-assembled network [18]. This reliance on fluorescence labels or dyes leading to a

• highly sensitive cantilever to measure the nanometre to sub-millimetre surface morphology. Attractive or repulsive interactions between the surface and the cantilever induce a bending force in the cantilever providing a mechanical means of probing the surface nanostructure [11]. There are various modes

• away accumulated surface electrostatic charge [30]. Furthermore, the requirement that TEM samples are prepared as thin films in order to allow electrons to be transmitted through the sample may require mechanical abrasion or ‘blotting’ of the sample to achieve this [14]. Supramolecular materials which

Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• by РсМ. As described in [13] to a three-necked flask of 100 mL capacity, equipped with a mechanical stirrer, a thermometer, and a reflux condenser, containing 10 mL of distilled water, was added 0.023 mol of the corresponding uracil 1 or 4, followed by the addition of 11 mL of a previously prepared

• ) With addition of H2O2. To a three-necked flask equipped with a mechanical stirrer, a thermometer, and a reflux condenser containing 10 mL of distilled water was added 0.023 mol of powdered uracil 1 or 4, followed by the addition of 11 mL of a previously prepared 24% NaOH solution to the obtained

• described in [13] in a three-necked flask of 100 mL capacity, equipped with a mechanical stirrer, a reflux condenser, and a dropping funnel, 0.022 mol of compound 2 or 5 was placed, 30 mL of distilled water were added and the mixture heated to 80 °C under constant stirring. Then, 0.022 mol of concentrated

Machine learning-guided strategies for reaction conditions design and optimization

• Lung-Yi Chen and
• Yi-Pei Li

Beilstein J. Org. Chem. 2024, 20, 2476–2492, doi:10.3762/bjoc.20.212

• computed by various methods [95]. These include substructure keys-based [96][97][98][99][100], circular [101][102][103], physicochemical [104][105][106][107], and quantum mechanical (QM) features [108][109][110][111][112]. The choice of descriptors depends on the size and scope of the dataset. For large

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• mechanical calculations is also increasing, such as a data set that considers propargylation reactions catalysed by bipyridine N,N’-dioxide-derived scaffolds, created by Wheeler and co-workers using their AARON toolkit [21][114][115][116]. Similar to experimental data, computational data sets also lead to

• molecule either by topological or quantum mechanical descriptors. The generality of a catalyst was then assigned by considering the fraction of clusters for which the average cluster enantioselectivity of a catalyst exceeds a user-defined threshold. This threshold can be used to balance the need for a wide

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• , the double azide addition reaction was applied to polymer crosslinking and the mechanical properties of the self-standing polymer films were compared. Results and Discussion Strain-promoted azide–alkyne cycloaddition Octadehydrodibenzo[12]annulene (DBA) with electron-withdrawing carbonyl substituents

• -standing film became insoluble due to the occurrence of strain-promoted double azide–alkyne cycloaddition (Figure 6a). The mechanical properties of the polymer films were then examined to observe the impact of crosslinking. A PVC-N3 film was prepared by a solvent-cast method on a Teflon boat. The strain

• -stress (S–S) curve of the PVC-N3 film exhibited a breakdown at the strain of >300% with a gradual increase in the stress (Figure 6b). This film did not display any yielding points (Figure 6c). Interestingly, the crosslinking with 5 dramatically changed the mechanical features. The crosslinked film showed

Electrochemical allylations in a deep eutectic solvent

• Sophia Taylor and
• Scott T. Handy

Beilstein J. Org. Chem. 2024, 20, 2217–2224, doi:10.3762/bjoc.20.189

• partial solubility of ethylene glycol in methoxycyclopentane as ethylene glycol could be clearly seen in the 1H NMR spectrum of the crude reaction extracts. It should also be noted that the lower isolated yields most likely reflect mechanical losses during extraction and chromatographic separation as the

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• of chemical processes [20][21], transporting and storing molecules [22], transducing and integrating information [23] providing structural and mechanical support [24], and generating movement [25], among other functions [26]. To fold and carry out their function properly, proteins often need post

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis

• Johannes Rocker,
• Till J. B. Zähringer,
• Matthias Schmitz,
• Till Opatz and
• Christoph Kerzig

Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106

• were thus carried out and they showed short-lived fluorescence and long-lived emission (phosphorescence) that was assigned to the triplet state of Aza-H with an energy of 2.32 eV (Figure 1A). Quantum mechanical computations of the Aza-H triplet state yielded a triplet energy of 2.17 eV (adiabatic

• Supporting Information File 72: General information, detailed experimental procedures, additional spectroscopic data, quantum-mechanical calculations, photostability and photoisomerization experiments. Funding We acknowledge generous financial support from the JGU Mainz and the German Federal Environmental

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• unique structure of fullerenes, characterized by a fully conjugated closed-cage structure, containing a mixture of hexagonal and pentagonal rings, have been recognized for the unique electronic [2][3][4], optical [5][6], and mechanical properties [7][8]. Despite the notable achievements in fullerene

Possible bi-stable structures of pyrenebutanoic acid-linked protein molecules adsorbed on graphene: theoretical study

• Yasuhiro Oishi,
• Motoharu Kitatani and
• Koichi Kusakabe

Beilstein J. Org. Chem. 2024, 20, 570–577, doi:10.3762/bjoc.20.49

• . Rotations around each bond can also happen and we expect similar steric hindrance effects to appear. Mechanical properties of PBA-linked molecular structure on graphene Here, we discuss possible conformations of the PBA-linked molecule. Would a similar activation barrier-type potential energy surface be

• antibody protein on graphitic material by a linker. The target antigen is introduced onto the sensor chips through antibody/antigen reaction. The present study is concerned with the mechanical deformation of the linker molecule. The mechanical properties of the rotational motion are almost the same whether

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• macroscopic analogs, exhibit mechanical motion between an open and closed conformation in response to stimuli. Such systems constitute an essential component of artificial molecular machines. This review will present selected examples of switchable molecular tweezers and their potential applications. The

• , and molecular machines. In particular, the advent of artificial molecular machines [13][14], consisting of an assembly of molecular components that perform mechanical-like motions in response to specific stimuli, has inspired the development of stimuli-responsive molecular tweezers, which have

• , the incorporation of responsive functionalities into molecular tweezers not only provides significant benefits in catalysis for the development of switchable catalysts but also extends their utility to molecular magnetism, where magnetic switches exploit mechanical motion, and to molecular electronics

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• , but the second fluorination step occurs only after reaction for several days. In the solid phase, mechanical milling of the diketone substrate with solid Selectfluor in the presence of sodium carbonate [13][14], and reaction of ketones with a strong base and an N–F reagent give rise to the

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

Long oligodeoxynucleotides: chemical synthesis, isolation via catching-by-polymerization, verification via sequencing, and gene expression demonstration

• Yipeng Yin,
• Reed Arneson,
• Alexander Apostle,
• Adikari M. D. N. Eriyagama,
• Komal Chillar,
• Emma Burke,
• Martina Jahfetson,
• Yinan Yuan and
• Shiyue Fang

Beilstein J. Org. Chem. 2023, 19, 1957–1965, doi:10.3762/bjoc.19.146

• File 1 for details). To block any hydroxy groups on the surface of CPG that were not capped, including those resulted from mechanical breakage of CPG, before commencing a synthesis, the CPG was subjected to typical capping conditions for 20 minutes. To reduce steric hindrance within the pores of CPG

Quinoxaline derivatives as attractive electron-transporting materials

• Zeeshan Abid,
• Liaqat Ali,
• Sughra Gulzar,
• Faiza Wahad,
• Raja Shahid Ashraf and
• Christian B. Nielsen

Beilstein J. Org. Chem. 2023, 19, 1694–1712, doi:10.3762/bjoc.19.124

• functionalities, and optimizing the π-conjugated backbone structure of Qxs, significant advancements have been made. These approaches effectively address key concerns and obstacles, resulting in red-shifted absorption and emission maxima, improved nonlinear optical properties, solvatochromism, mechanical

• in emission properties through mechanical stimulation offers exciting possibilities for optomechanical applications [68]. Another notable strategy, performed by Gupta and co-workers, involves fine-tuning of the electron accepting tendency of quinoxaline by incorporating various groups with different

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• is that it is difficult to completely rule out chain transfer to the solvent. Therefore, obtaining very high molecular weight product through solution polymerization is tough. Suspension polymerization is a heterogeneous process and requires the use of a mechanical agitation to mix monomers and

• refractive index from tetravinylsilane, ethanedithiol, and benzenedithiol. Polymers made by thiol–ene polymerization usually have well-ordered molecular networks. This character gives thiol–ene polymers highly tunable mechanical response hence it shows great application potential in additive manufacturing

• type of post-polymerization modification introduces or removes functionalities at polymer chain ends [120]. 3.2 Chemical crosslinking of polymers Chemical crosslinking is a suitable approach to increase chemical resistance [121], mechanical strength [122], and other properties [123] of polymers. In

Light-responsive rotaxane-based materials: inducing motion in the solid state

• Adrian Saura-Sanmartin

Beilstein J. Org. Chem. 2023, 19, 873–880, doi:10.3762/bjoc.19.64

• mechanical bond, such as control over the dynamics of the components upon application of external stimuli. This perspective aims to highlight the relevance of these materials, by pointing out recent examples of photoresponsive materials prepared from a rotaxanated architecture in which motion of the

• -responsive materials; mechanical bond; mechanically interlocked materials; rotaxanes; Introduction Light turns out to be a suitable and tailorable stimulus in order to develop materials showing improved functionalities, such as those of smart materials [1][2][3][4][5]. The characteristics of light which

• azobenzene and ferrocene motifs (Figure 1a). The azobenzene scaffolds play a dual role, both as the engine transforming photoenergy into mechanical motion via trans/cis photoisomerization upon UV light input and as a modulator of the crystalline packing by varying the para-substituent R1, which leads to

Bromination of endo-7-norbornene derivatives revisited: failure of a computational NMR method in elucidating the configuration of an organic structure

• Demet Demirci Gültekin,
• Arif Daştan,
• Yavuz Taşkesenligil,
• Cavit Kazaz,
• Yunus Zorlu and
• Metin Balci

Beilstein J. Org. Chem. 2023, 19, 764–770, doi:10.3762/bjoc.19.56

• configuration in a molecule, in short, it is the single most important spectroscopic tool aside from X-ray crystallography to provide an accurate ensemble-guided view of the structure, even conformational dynamics in a molecule. Quantum mechanical/nuclear magnetic resonance (NMR) approaches are used for the