Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• pharmacological properties and may find application in the design of new promising medications. Herein, we present a convenient synthetic approach for the preparation of previously unknown [1,2,5]oxadiazolo[3,4-d][1,2,3]triazin-7(6H)-one heterocyclic systems containing both a furoxan/furazan fragment condensed to

• obtained using NaNO2 in an AcOH + MeSO3H [1:1] solution (Table 1, entry 7). Organic solvents (CH2Cl2, MeCN) were not applied due to a known rapid decomposition of the generated (1,2,5-oxadiazolyl)diazonium salts [42]. The optimized conditions were applied for the preparation of [1,2,5]oxadiazolo[3,4-d

• found to be suitable for the preparation of a library of new biheterocyclic molecules bearing aromatic and aliphatic substituents as well as incorporating amino acid residues. The obtained furoxanotriazinones have demonstrated a moderate NO-releasing ability across a wide range of concentrations under

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

• identifications [17][18][19][20][21][22]. All parts of the chemical proteomics experimental procedure, the sample preparation together with MS measurement and evaluation can be performed in a streamlined or automated way using sophisticated pipelines [13][17][21][25][26][27]. These are highly optimized to provide

• -azido-1-propanamine to give the desired AzidoTMT linker. Furthermore, Makarov et al. developed a linker containing a sulfoxide (SOX) group, which is well-known for specific fragmentation releasing the reporter ion at m/z 179.0849 (Figure 7C) [81][86][87]. The preparation of the tag is based on a five

• enzymatic cleavage. In particular, when considering the linker preparation, the biotin–DADPS–azide can be synthetized in only two steps [112]. Finally, the development of multifunctional linkers enables to combine the in-gel and MS-based analysis in one experiment [116][117][118][119][120]. The

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• challenging iminoiodinanes). In situ preparation of the iminoiodinane intermediates is possible, and for those reagents that undergo facile decomposition, aziridination is more efficient using these conditions (yields for in situ-generated iminoiodinanes are in parentheses in Scheme 3, with N-o-methyl (6g

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• , Tucson, Arizona, 85721, USA 10.3762/bjoc.20.195 Abstract The utility of bio-isosteres is broad in drug discovery and methodology herein enables the preparation of deuterium-labeled products is the most fundamental of known bio-isosteric replacements. As such we report the use of both [D1]-aldehydes and

• analyses of microsomal stability confirm prolongation of t1/2 of the new deuterated analogs. We also report the first preparation of [D2]-isonitriles from [D3]-formamides via a modified Leuckart–Wallach reaction and their use in an MCR to afford products with [D2]-benzylic positions and likely

• a >95% deuterated aldehyde gave a >95% deuterated product. The low yield in 2c is likely due to the difficult preparation of aliphatic deuterated aldehydes which led us to believe that the starting material was partially decomposed. Nonetheless, both aliphatic and aromatic deuterated aldehydes have

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

• Additives and preparation of deep eutectic solvents The selected additives are supposed to shift the properties of the reaction solution in more extreme directions or are interesting for other reasons. PEG-8000 (Sigma, Darmstadt, Germany) is a molecular crowder that is used in the CFPS system by default

• the described strains E. coli BL21(DE3) pAR1219 for extract preparation and E. coli DH5α pETH6sfGFP and E. coli DH5α pETSUMOthscGASGFP for plasmid production. Minor variations are stated in the following. The preculture for extract preparation was grown for 20 h at 200 rpm and 37 °C, centrifugation

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• synthetic method for the preparation of β-keto thioesters and β-keto amides remains imperative. Organic reactions in water are an important and exciting research topic of green chemistry because water as a solvent exhibits fascinating features, such as low cost, good environmental compatibility, nontoxicity

• , the optimized reaction conditions for the synthesis of 2a were determined to be 1.0 equiv of DBSA as catalyst and reflux temperature (conditions A). Subsequently, we turned our attention to the hydrolysis reaction in the presence of hydroxide for the preparation of 3-oxo-N,3-diphenylpropanamide (3a

• silica gel 60 F200) were analyzed under UV light (254 nm). Chromatographic purifications were performed on SDZF silica gel 160. The starting α-oxo ketene N,S-acetals 1 are known compounds [40][41] and easily prepared according to References [40][58]. Typical procedure for the preparation of β-keto

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

• demonstrate efficient and near quantitative recovery of the metal by electrolysis after product extraction and this recovered metal can be used again for further allylations. Further efforts to improve the efficiency and enable catalytic metal use are underway. Experimental Preparation of deep eutectic

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• . α-Amination of ethyl 2-oxocyclopentanecarboxylate catalysed by PS-THU which could be recycled over 9 reaction cycles. Preparation of supported catalysts C29–C31 from cinchona squaramides 29–31 modified with a primary amino group. Application of PGMA-supported organocatalysts C29–C31 in the

From perfluoroalkyl aryl sulfoxides to ortho thioethers

• Yang Li,
• Guillaume Dagousset,
• Emmanuel Magnier and
• Bruce Pégot

Beilstein J. Org. Chem. 2024, 20, 2108–2113, doi:10.3762/bjoc.20.181

• (Scheme 1d). It is important to mention that during the preparation of this paper, a similar study appeared. Peng and co-workers demonstrated the efficient use of acetonitrile as nucleophile with various aryl difluoroalkyl sulfoxides but only one example of an SCF3 compound was reported [49]. Results and

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

• the field of computational chemistry and bioinformatics. It is extensively used to model and simulate the dynamic behaviour of various molecular systems, including proteins, nucleic acids, lipids, and small molecules. GROMACS provides various tools for system preparation, simulation setup, and post

• precise scoring function, and smooth integration with other molecular modelling programs. Additionally, FlexX excels in processing large libraries at high speed and is user-friendly, requiring no prior receptor preparation. 4. ROSETTA [134]: The development of GlycanDock [134], a protein−glycoligand

Cage-like microstructures via sequential Ugi reactions in aqueous emulsions

• Rita S. Alqubelat,
• Yaroslava A. Menzorova and
• Maxim A. Mironov

Beilstein J. Org. Chem. 2024, 20, 2078–2083, doi:10.3762/bjoc.20.179

• colloidal particles on the formation of the surface in Pickering emulsions, we varied the conditions for their preparation. Specifically, we increased or decreased the cross-linking density using the Ugi reaction at the first (formation of colloidal particles) and second stages of the process (formation of

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• , product 17a shows cytotoxic activity against Hep G2 hepatocellular carcinoma and MCF-7 breast carcinoma cell lines. The synthesis of 3,5-bis(arylamino)pyrazoles 21 involves the preparation of bisarylthioamides 22 via nucleophilic addition and double retro-Claisen condensation of isothiocyanates 19 and

• cyclocondensation with 1,3-dicarbonyl compounds [57]. In their program to synthesize regioselectively substituted pyrazoles, Raw and Turner established the one-pot preparation of triply substituted pyrazoles 27 and 28 via 1-formyl-1-methylhydrazine (29), generated in situ by reacting methylhydrazine and ethyl

• 47, can be accessed from polyfunctional hydrazine derivatives via multicomponent reactions. For the preparation of pyrazoles 47, 4-amino-5-hydrazinyl-4H-1,2,4-triazole-3-thiol (44), phenylacyl bromides 45, and benzoylacetonitriles 46 were chosen as starting materials (Scheme 13) [67]. Thereby

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

• purification system. Hydrobromic acid (48%) and deuterium oxide (99.9 atom %) were supplied by Merck. Sample preparation To produce micellar samples, light-responsive PS were shaken with the solvent (50 mM in either H2O or D2O) until homogenous. For samples of higher concentration, AAPTAB was added to water

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• asymmetric preparation of chiral amines through the addition of nucleophilic partners [21][22] while the azaenamine character of some aldehyde-derived hydrazones has been demonstrated in the coupling with suitable electrophiles such as Michael acceptors [23][24]. Last but not least, the C=N bond of

• electrochemical approach constitutes an advantageous alternative to previous methods, which required the preparation of difficult-to-handle hydrazonoyl halides for the synthesis of 1-aryl-5-amino-1,2,4-triazoles from cyanamide [56][57]. Pyrazolines are highly important heterocyclic motifs in pharmaceutical and

• aldehyde hydrazones and alkenes for the preparation of pyrazolines was proposed by Tong, Song, et al., achieving similar efficiency using oxone/KBr as an environmentally friendly oxidative system [59]. Most recently, Zhou and Ma et al. described the electrochemical access to 3‑aminopyrazoles 79 from

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• 1,2-difluoroethylene (HFO-1132). The major routes for the preparation of the E- and Z-isomer of HFO-1132 are reviewed, along with the chemistry in radical, nucleophilic, and electrophilic reactions. Keywords: 1,2-difluoroethylene; fluorinated monomers; HFO-1132; hydrofluoroolefins; radical reactions

• claimed to be a potential monomer for the preparation of new fluoropolymers [43][44]. Despite the fact that HFO-1132 has been known for a long time, there are no publications that summarize the chemistry of the compound. With this in mind, the main methods for the preparation of (E/Z)-1,2-difluoroethylene

• are discussed in this Review article. Special attention is given to the role of 1,2-difluoroethylene in multiple reaction types. Review Preparation of HFO-1132 In scientific literature, the number of publications on the synthesis of 1,2-difluoroethylene is limited. HFO-1132 was first obtained in 1955

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• and mild Mitsunobu conditions for the preparation of N2-substituted indazole analogs 16a–q. By directly reacting compound 6 with alcohols 13a–q (2 equiv), diethyl azodicarboxylate (DEAD, 2 equiv), and triphenylphosphine (TPP, 2 equiv) in THF at 50 °C (conditions B), the corresponding N2-substituted

• found in Supporting Information File 1. General procedure for the N1-alkylation using alkyltosylates Preparation of methyl 5-bromo-1-methy-1H-indazole-3-carboxylate (15a) To a solution of methyl 5-bromo-1H-indazole-3-carboxylate (300 mg, 1.176 mmol) in dioxane (10 mL) at room temperature was added

• , 268.9902. General procedure for the N2-alkylation using Mitsunobu conditions Preparation of methyl 5-bromo-2-methyl-2H-indazole-3-carboxylate (16a) To a solution of methyl 5-bromo-1H-indazole-3-carboxylate (1.384 g, 5.43 mmol) in THF (15 mL) was added triphenylphosphine (2.85 g, 10.85 mmol) and methanol

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• crucial function in many biological processes. Due to their bifunctional character, they have been also used for combinatorial chemistry purposes, such as the preparation of DNA-encoded chemical libraries. We developed a practical synthesis for α-heteroaryl-α-amino acids starting from an array of small

• ][28]. However, the selectivity of these photoredox reactions is driven by the structural properties of the heteroaromatic ring. During the preparation of this article, the Meggers group published an outstanding enantioselective iron-catalyzed α-amination pathway (Scheme 1b) [29]. The method is widely

• amino group by reduction. We reasoned that increasing the sp2 fraction and the rigidity of the whole structure will lead to increased stability of these derivatives. The first exploratory attempts demonstrated the easy preparation and the high bench stability of the oxime derivatives, therefore we opted

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• option for the preparation of isoquinolinone derivatives. In 2020, two reports have been published on the conversion of alkyne-tethered N-alkoxybenzamides to isoquinolinones by intramolecular oxidative annulation, either electrochemically or using the hypervalent iodine reagent phenyliodine(III

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• versatile methods for the preparation of structurally diverse β-lactam derivatives is of great importance and relevance. Continuing the investigation of the reactivity and synthetic potential of diazotetramic acids (1), we have recently shown that these diazo reagents can act as precursors of β-lactam

• ; reaction scale – 0.25 mmol; ascaled-up (1.5 mmol) yield. Negative results with several N-, O-, and C-nucleophiles and with diazo reagent 1m. Preparation of acids 4 by hydrogenolysis of benzyl esters and examples of acid 4a amidation. Supporting Information Deposition Number CCDC 2323689 (for 3t) contains

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

• . Brunschweiger et al. employed the compartmentation strategy to overcome synthetic problems related to the preparation of a DNA-encoded GBB library [17]. DNA-encoded libraries (DELs) are widely used in screening projects, allowing the synthesis of a huge number of compounds as pools, and the identification of

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

• -type syntheses, MCRs have become helpful tools for more efficient preparation of chemical libraries with higher molecular diversity and complexity in fewer steps and less time [28][29]. Considering the limitations of existing methods, as well as the applications of 5-aryldeazaalloxazines 2, and in the

• (1H,3H)-dione) by refluxing with thionyl chloride [20][23]. However, the preparation of partially hydrogenated 5,10-dihydropyrimido[4,5-b]quinolinediones has been repeatedly reported by one-pot condensation of substituted anilines, aldehydes and barbituric acids, usually in protic solvents (alcohols

Chiral bifunctional sulfide-catalyzed enantioselective bromolactonizations of α- and β-substituted 5-hexenoic acids

• Sao Sumida,
• Ken Okuno,
• Taiki Mori,
• Yasuaki Furuya and
• Seiji Shirakawa

Beilstein J. Org. Chem. 2024, 20, 1794–1799, doi:10.3762/bjoc.20.158

• ; enantioselectivity; halogenation; lactones; organocatalysis; Introduction Catalytic asymmetric halolactonizations of alkenoic acids are powerful methods for the preparation of important chiral lactones in enantioenriched forms [1][2][3][4][5][6][7][8][9][10][11]. A wide variety of chiral catalysts have been applied

Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• investigate hypervalent iodine(V) fluorides has been limited primarily by their difficult preparation traditionally using harsh fluorinating reagents such as trifluoromethyl hypofluorite and bromine trifluoride. Here, we report a mild and efficient route using Selectfluor to deliver hypervalent iodine(V

• ) fluorides by reacting iodine(III) precursors with commercially available Selectfluor. The method avoids large excesses of reagents and pure iodine(V) fluorides are isolated after a simple work-up. Results and Discussion Preparation of bicyclic difluoro(aryl)-λ5-iodanes Two different types of bicyclic

• protocol using TCCA (4 equivalents) and KF (6 equivalents) was then applied to both bicyclic iodine(III) amides 11a and 11b, but these reactions also failed to form either difluoroiodane 7a or 7b. Following the successful preparation and isolation of difluoroiodane 6, we investigated its ability to

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• bisamides based on the same aldehydes and amines may also demonstrate biological activity. In view of these facts, we decided to develop a new approach for the synthesis of hybrid molecules containing substituted heterocyclic and peptidomimetic moieties. The first stage of this approach was the preparation