Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• ]. Moreover, the parent diazocine is insoluble in water (precipitation in water/DMSO > 9:1). Substitution with polar substituents such as CH2NH2 provides water solubility, however, it does not restore the high Z → E conversion rates of the parent system in organic solvents, which is a disadvantage, since

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

• on solvents. In fact, high concentrations of reagents or products can lead to precipitation, causing undesired clogging of the reactor and potentially disastrous consequences for the intended transformation. It is important to mention that specific solutions for handling slurries in flow have been

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• self-directing and self-correcting, and the term “self-assembly” [290][291][292] often used [286][293][294][295][296]. Products can be thermodynamic or kinetic, but are often isolated by precipitation due to low solubility [297], though many have useful solubility [288][298]. Since POCs typically have

• able to adapt this chemistry to work in situ, allowing soluble metastable imine frameworks to be trapped as amides [38]. The adapted cages were soluble, and were now stable enough to be purified by gel-permeation (size-exclusion) chromatography (useful when precipitation is not possible), which is

• low-symmetry conformation of cage 3 in solution [39]. Due to their stability, we can typically reclaim our cages up to quantitatively after binding or catalysis experiments, often just via a work-up and precipitation. This breadth of available data opens considerable opportunities in computational and

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• diluted with cold water and acidified with 5% cold HCl. The solution was allowed to stand for 15 minutes to complete precipitation. Precipitates were collected via filtration and washed with excess distilled water. The dried product was then recrystallized from absolute ethanol. Synthesis of pyrazolo-1,2

• concentration under vacuum. It was then diluted with cold water and acidified with 5% cold HCl. The solution was allowed to stand for 15 minutes to complete precipitation. Precipitates were collected via filtration and washed with excess distilled water. The dried product was then recrystallized from absolute

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• synthesis was efficient and rapid as the final adducts could be isolated only by precipitation. In addition, the reactions were performed in a parallel setup using custom-made metal blocks. Specifically, thienopyrimidine and thienopyrimidone derivatives exhibit a range of biological activities, i.e

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• suspensions and precipitation of the starting materials, make these solvents unsuitable for this reaction and the isolation of the products troublesome. The use of 2-propanol/water (2:1), together with the application of heat, ensures optimal solubility of the species involved. Moreover, the workup procedure

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

• structure analysis, and is purified by simple precipitation without requiring chromatography; (3) various end-capping agents are available, and well-optimized conditions can ensure a high yield (e.g., 2-methoxyphenyl isocyanate obtains an 85% yield after 3 h of reaction [49]). Owing to such a high-yield

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

• removal of Na2S followed by the precipitation and re-addition of Cu2+ ions (Figure 5). Comprehensive selectivity studies were conducted with various anions/sulfur compounds (SO42−, SO32−, S2O52−, S2O42−, S2O32−, ClO−, OAc−, NO3−, I−, HCO3−, CO32−, Cl−, lipoic acid, and glutathione, as depicted in Figure 6

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• easily recovered by precipitation using polar solvents. This catalyst proved to be excellent for the preparation of (S)-baclofen on a gram scale, furnishing the main chiral intermediate in high yield and enantioselectivity. Furthermore, the catalyst was recycled over five cycles while maintaining its

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• or scale down and partially automatize the protocol or both. The standard mass spectrometry-based chemical proteomics workflow requires up to 1 mg of total protein, acetone protein precipitation after the ‘click’ reaction to remove the excess of the biotin-containing reagent, desalting of the

• probe–proteins enrichment [94]. The underlying and unifying advantage of these protocols is the use of a mixture of hydrophilic and lipophilic carboxylate-coated magnetic beads to replace the protein acetone precipitation after CuAAC. After the ‘click’ between the probe–protein conjugates and affinity

Cell-free protein synthesis with technical additives – expanding the parameter space of in vitro gene expression

• Tabea Bartsch,
• Stephan Lütz and
• Katrin Rosenthal

Beilstein J. Org. Chem. 2024, 20, 2242–2253, doi:10.3762/bjoc.20.192

• precipitation of proteins [54], which would decrease the amount of detectable CFPS product. Other publications describe that the solubility of proteins can be improved with increasing salt concentration by the addition of NaCl [55]. Testing of other salts at high concentrations is necessary to clarify whether

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• -withdrawing group improves the stability of the product 4 (R = p-O2N-C6H4, E = PhSe) and also because phase separation is caused by the product precipitation from the reaction solution. On the other hand, the addition reaction of (PhTe)2 to isocyanides does not proceed at all [30]. This is because the

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• derivatization, allowed the obtainment of 18 in high yield under relatively mild conditions, and was extended to the synthesis of 23 analogues, all in high yields (>86%). The catalyst could be recovered from the reaction medium by precipitation and reused up to five times without loss in activity. In 2020, Tyagi

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• derivatives, 2i–l and 2m–p, respectively, was accompanied by several complications, and the isolation of the products required precipitation with 2-propanol in several cases. The heating time was prolonged to two days for 8-methoxy derivatives 2m–p, nevertheless giving moderate yields. For 7-methoxy

• . aReaction was done in DMF/AlCl3. bIsolation requires precipitation with 2-propanol. c2 days. Control experiments related to bulky substituted aldehydes. Optimization of the reaction conditions for the synthesis of 2a. Supporting Information Supporting Information File 28: Spectroscopic and analytical data

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• order to improve the synthesis of this fused heterocycle, different strategies were tried, e.g., performing the Ugi reaction in different solvents (dichloromethane, ethyl acetate, methanol) to prevent the precipitation of benzodiazepine 5c, conducting the Ugi reaction in boiling methanol or treating the

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• pentacyclic secondary amine 97 bearing the ester linker in the C1 side chain in one pot. After removal of SfmC by precipitation and centrifugation, the reaction mixture containing secondary amine 97 was subjected to the reductive amination using 2-picoline borane as a hydride source, yielding tertiary amine

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• precipitation with a hexane–ether mixture and was found to be of sufficient purity for spectroscopic analysis. If desired, the product can be crystallized from an EtOAc–MeOH mixture for further purification. On the other hand, compound 2a has also been previously investigated for its potential covalent prolyl

• transformations is the purification of the synthesized product, since these oils are non-volatile and non-polar. However, in this study, the choice of these materials as green solvents allows convenient isolation of the cycloadducts by precipitation followed by filtration with hexane or diethyl ether. Thus, IMDAF

Kinetically stabilized 1,3-diarylisobenzofurans and the possibility of preparing large, persistent isoacenofurans with unusually small HOMO–LUMO gaps

• Qian Liu and
• Glen P. Miller

Beilstein J. Org. Chem. 2024, 20, 1099–1110, doi:10.3762/bjoc.20.97

• mL glacial acetic acid. After attaching a reflux condenser, the mixture was heated to reflux for 12 hours with stirring. The hot reaction solution was filtered. To the hot filtrate was added 5 mL of cold water leading to the precipitation of crude product. The crude product was vacuum filtered

• mmol), zinc dust (1.15 g, 17.6 mmol) and 13 mL glacial acetic acid. After attaching a reflux condenser, the mixture was heated to reflux for 12 hours with stirring. The hot reaction solution was filtered. To the hot filtrate was added 5 mL of cold water leading to precipitation of crude product. The

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• better solubility in organic solvents than benzyl bromides, reducing precipitation issues. Applying now the first-ring-then-benzylic halogenation strategy to p-xylene, dibromide 3b was successfully converted into 3c, by means of the method herein developed for the benzylic bromination. The process was

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• precipitation occurred and precipitates were subsequently collected via vacuum filtration with no exception for any DPQDs 1b–6b. The yields obtained in this step were moderate to excellent (61–99%). Target 7b was synthesized from 12 and 7e via the in situ generation of 7a and subsequent SNAr with KOH given the

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• anhydrous THF, MeCN, and dioxane, using such azide sources as NaN3, LiN3, and TMS-N3. Full conversion towards product 12a was observed by HPLC with NaN3 in anhydrous DMF. However, precipitation, direct, and reversed-phase column chromatography provided low yields (Scheme 5) due to the degradation of the

Enhanced reactivity of Li⁺@C₆₀ toward thermal [2 + 2] cycloaddition by encapsulated Li⁺ Lewis acid

• Hiroshi Ueno,
• Yu Yamazaki,
• Hiroshi Okada,
• Fuminori Misaizu,
• Ken Kokubo and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2024, 20, 653–660, doi:10.3762/bjoc.20.58

• mM LiTFSI; column: Buckyprep (Nacalai tesque), ø 10 × (20 + 250) mm. The fraction containing Li+@C60{(4-MeOC6H4)CH=CH2} was concentrated under reduced pressure. The desired monoadduct Li+@C60{(4-MeOC6H4)CH=CH2} TFSI− (5b, 5.6 mg, 4.9 µmol, 53%) was afforded by precipitation with diethyl ether and

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• furnished good results for the HPW-catalyzed GBB-3CR with yields greater than 63% (5m–o). It is always important to point out the limitations of a given method and in our case, we did have some. Purification by column chromatography became necessary since product isolation by precipitation was not effective

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

• nanoparticles to conduct the Friedel–Crafts reaction between indoles and aldehydes [104]. In an effort to synthesize the sulfated zirconia nanocompounds, a new two-step precipitation method was developed. The first step involved the employment of zirconium oxychloride and its precipitation with ammonium

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• the other components of the reaction mixture. The lipophilic O-alkylated gallic acid unit increases the solubility of the organocatalyst in less polar solvents, such as DCM or toluene but leads to the precipitation of the organocatalyst in polar solvents, including MeOH or MeCN. As a result, the

• acid ester 9 was hydrolyzed under basic conditions in an ethanol/water mixture. After the reaction, the pH of the mixture was adjusted to 4 with hydrochloric acid, which resulted in the precipitation of the product 10 in excellent yield (95%). Next, carboxylic acid 10 was converted into the

• carry out the catalytic reaction homogeneously. The solubility of the lipophilic catalyst 2 was investigated in ten solvents with low polarity, including a new, bio-based polar aprotic solvent, MeSesamol [33]. The catalyst’s precipitation – which is necessary for its recycling – was tested by adding a