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

• footprint of organic reactions [12][13]. Beyond environmental benefits and enhanced human safety, mechanochemical reactions often feature shorter reaction times, eliminate the need for external heating, and offer alternative product selectivity [3][14]. In general, such reactions are characterized by the

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• standing. Also, it has been reported that the generation of the hydroperoxide may be accelerated by heating the solvent under open atmospheric conditions [19]. We envisaged that such autooxidation of THF [20] will produce THF hydroperoxide, and this will facilitate the transformation of 3-arylbenzofuran-2

• use of a hydroperoxide generating solvent made the protocol operationally simple. To investigate the generality of the protocol, the previously synthesized 3-arylbenzofuran-2(3H)-ones 3aa–ka were treated with 1.0 equiv Cs2CO3 in THF under open atmospheric heating. As revealed in Scheme 2, the reaction

• a bulky substitution at the 7-position of the benzofuranone also hinders the formation of 2-hydroxybenzophenone, we prepared 3,7-diphenylbenzofuran-2-one (3ma). However, on heating 3ma with Cs2CO3 in THF, the corresponding benzophenone 4ma was obtained, which confirmed that a bulky substituent in

Deciphering the mechanism of γ-cyclodextrin’s hydrophobic cavity hydration: an integrated experimental and theoretical study

• Stiliyana Pereva,
• Stefan Dobrev,
• Tsveta Sarafska,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2024, 20, 2635–2643, doi:10.3762/bjoc.20.221

• upon heating. Conclusion Using experimental and computational methods as well as available literature data, the present study reliably estimates the number of water molecules present in γ-CD, their preferable binding position, and thermal stability. Comparison with the other cyclodextrins revealed that

• Differential Scanning Calorimeter. The samples were placed in aluminum pans and heated in the temperature range between 300–440 K at a constant rate of 10 °C min−1 under pure nitrogen atmosphere. Similarly, thermogravimetric measurements were conducted using DTA/TG (TA-SDT 600) at the same heating rate and

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

• determined that room temperature is inadequate for fully oxidizing substrates. The optimal oxidation temperature for uracils 1 and 4 is between 60–65 °C, whereas for pyridines 7 and 9 it is 45 °C. Heating the reaction mixture at a temperature higher than the optimum level causes the substrates to be

• % after 10 h of heating [36]. It is essential to include 2–3 equiv of H2O2 to obtain the best result (Table 4). The analysis of the results obtained from Table 3 and Table 4 indicates that the binary oxidation system of APS/H2O2 consumes APS more slowly and therefore the substrates (MU, TMU, and Py) are

Base-promoted cascade recyclization of allomaltol derivatives containing an amide fragment into substituted 3-(1-hydroxyethylidene)tetronic acids

• Andrey N. Komogortsev,
• Constantine V. Milyutin and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 2585–2591, doi:10.3762/bjoc.20.217

• the reactions that require heating. General experimental procedure for the synthesis of tetronic acids 4 A mixture of corresponding amide 3 (1 mmol) and 1,1-carbonyldiimidazole (0.49 g, 3 mmol) was stirred in acetonitrile (7 ml) for 5 min at room temperature, then DBU (0.17 g, 1.1 mmol) was added and

Transition-metal-free synthesis of arylboronates via thermal generation of aryl radicals from triarylbismuthines in air

• Yuki Yamamoto,
• Yuki Konakazawa,
• Kohsuke Fujiwara and
• Akiya Ogawa

Beilstein J. Org. Chem. 2024, 20, 2577–2584, doi:10.3762/bjoc.20.216

• under transition-metal-free and open-air conditions. Conventional methods required photoirradiation or electrolysis to generate aryl radicals from triarylbismuthines. In this study, it was found that simply heating the solution of triarylbismuthines in benzotrifluoride (BTF) in air successfully led to

• reaction conditions were harsh, requiring heating at 260 °C for several days [50]. Thus, only two examples of the use of triarylbismuthines as aryl radical sources have been reported for the synthesis of arylboronates, which proceeds under light irradiation conditions (Scheme 1a) [47][48]. Our group has

• investigated various transition-metal-free methods for the generation of aryl radicals from shelf-stable aryl compounds (Scheme 1b). For example, the heating of arylhydrazine hydrochlorides (ArNHNH2·HCl) in the presence of base under open-air conditions successfully led to the generation of aryl radicals and

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• ]. Iodoethane was also shown to be an effective reagent furnishing the product in up to 56% upon heating to 40 °C (Table 1, entries 11 and 12). It was envisaged that oxidation of iodoethane led to formation of oxidized forms of iodide by C–I-bond cleavage, therefore tetrabutylammonium iodide was utilized to see

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

• increased the overall yield of the reaction (Table 1, entry 5). In summary, minimal formamide (1–2 equiv), excess [D2]-formic acid, and heating to 170 °C in a microwave reactor for 5 minutes is expected to give excellent yields in good deuteration %. A tentative mechanism to [D3]-formamides is shown in

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• 0.267/0.305) substituents reacted with primary and secondary alkylamines, requiring prolonged heating and a 1.5 excess of amine (Scheme 4), to give meta-substituted arylamines in reasonable synthetic yields. In the case of 1,3-diketone 1d, the addition of molecular sieves is necessary in order to reduce

• reaction of 1,3-diketones 1e and 1f with aliphatic amines was expected. Indeed, the reaction of 1,3-diketones 1e or 1f with benzylamine was sluggish, and a number of undefined side-products were formed (LC control). m-Isoxazole arylamine 3ea was isolated in low yield (21%) after heating for 6 days (Scheme

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• using simplest heating in acetic acid (Table 1, entries 13–16). After some playing with temperature, reaction time, and ratio of starting reagents we ultimately found conditions (AcOH, 110 oC, 4 h) suitable best for our chemistry and leading to the yield of the target product 2a 74% (Table 1, entry 16

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

• –heteroatom bonded compound (E–E) upon heating or photoirradiation. Similarly, E• adds to 1 to form 2, which undergoes atom (or group)-transfer from E–E to give the 1,1-addition product 4 with regeneration of E• [17][18]. In method 3, the photoinduced redox reaction of a heteroatom compound takes place using

• methods, methods 1 and 3 require the addition of a radical initiator and a photocatalyst, respectively. In contrast, method 2 does not require any additive, although, if the heating or photoirradiation is performed by electricity, the combustion of fossil fuels may cause environmental pollution. However

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

• their ability to be engaged in such a rearrangement [4][5]. Upon activation with trifluoromethanesulfonic anhydride and under heating, we showed their transformation to ortho thioethers with a fairly acceptable selectivity towards the pathway of sulfilimine synthesis (Scheme 1b). Following our seminal

• Discussion We started our optimization with the reaction between acetonitrile and phenyl trifluoromethyl sulfoxide (1a, Table 1). We firstly chose the same stoichiometry as described in our previous study and tried to reduce the reaction time by the help of microwave heating (Table 1, entry 1). Under these

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

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

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

• pattern to that of the native, E isomer (Figure 2). Changes occur immediately, after 1 s of X-ray exposure, and saturate after ca. 5 s. The changes are comparable to those observed on Z–E isomerisation induced using blue (460 nm) light or heating to 55 °C but occur at a much faster rate (Figure S2

• the micelle shape of this isomer. The fast rate of the morphology change, in comparison to using blue light or heating to 55 °C, shows rapid rates of Z–E isomerisation from X-ray-induced catalysis, which may be due to the presence of multiple different catalysing species and therefore isomerisation

• that Z–E isomerisation cannot be easily induced using gentle heating or visible light, as shown by the stability of the UV–vis absorbance spectra and SAXS patterns under these conditions (Figures S1 and S3, Supporting Information File 1). In contrast, irradiation with X-rays leads to significant

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

• prepared prior to the electrolysis through the condensation of 2-hydrazinopyridine 13 and various aromatic, aliphatic and α,β-unsaturated aldehydes 14. The electrooxidative transformation was performed under constant current at 7 mA in a mixture of acetonitrile and water under heating. From a mechanistic

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

• )acetate at the bottom of the vial after a few hours of storage in the fridge. The solid can be easily re-dissolved by gentle heating, and without affecting the product concentration and integrity. After a brief screening, Pd(dba)2 and X-Phos (in a 1:2 ratio) were selected as the catalyst system for the

• screening and rapid optimization [46][47]. Homogenous heating and mixing in flow reactors can lead to higher reaction rates and yields. In terms of photochemistry, continuous flow setups provide enhanced light irradiation as well [48][49]. These advantages make flow chemistry a powerful tool for chemical

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

• tested in a previous study [3]. The reaction requires rather severe heating under microwave irradiation (200 °C, chlorobenzene, sealed vial), ensuring complete conversion of the diazo compound in a rather short time. Initial experiments using p-anisidine as a nucleophile showed that the target β-lactam

• derivative 3a could be obtained in high yield (83%) after simple chromatographic separation of the reaction mixture (Scheme 2). When the synthesis was carried out using conventional heating in 1,2-dichlorobenzene (200 °C, 1 h), product 3a was obtained in slightly lower yield (75%), so further experiments

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

• earth (RE) triflates before the report by Longo et al. [5], who found La and Gd performing better than Eu and Yb, and similarly to Sc in a model reaction between 2-aminopyridine (1), benzaldehyde (2) and tert-butyl isocyanide to give 3 under microwave (MW) heating. However, when methyl isocyanoacetate

• temperature and then, upon addition of the boronic acid, heating at 60 °C (Scheme 9). Similar efficiencies were observed with a wide range of boronic acids (10 examples, 49–87% yield). The biohybrid was suitable also for gram-scale synthesis and for storage at room temperature under inert atmosphere, showing

• (OTf)3 (5 mol %) as acidic catalyst, and a non-microwave instant heating reactor, performing the reaction at 60 °C and obtaining 25 in 78% yield. Moving forward to investigate the scope of the reaction with different 2-aminoamidines and isocyanides, they obtained 18 different products with isolated

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

• heating conditions (CH). Syntheses were performed in DMSO, DMSO/AlCl3, DMF/AlCl3 and AcOH/H2SO4 at 110 °C (Table 1, entries 5, 6, 9, and 12). Under these conditions, the reaction time was significantly reduced to 1 hour from the usual 15 hours, however, the yields stayed in the range of 30%, and the

• reaction mixtures contained a large number of impurities. In summary, standard heating conditions exhibited distinct advantages over MW, and the reaction performance in DMSO was the most effective. Moreover, DMSO is considered an environmentally friendly solvent (for detailed information on reaction

• 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

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

• conventional thermal heating, amide 10a was isolated, albeit in a lower yield and accompanied with tar formation. In addition to the 1H, 13C NMR spectra and mass spectrometry data, the structure of compound 10d was established by X-ray diffraction analysis (Figure 3). It was also found that the substituents at

• for two days and then heating the reaction mixture in a closed vessel at 80 °C for 3 hours (Scheme 5). This procedure led to the formation and isolation of the products 10d and 12e with yields which are similar to the tandem reaction. Using the example of bisamide 8c, it was found that changing the

• corresponding amide 10. The expected fact that the amides 10 could not be formed from the ketobisamides 12 (Table 3) was also confirmed; stirring the latter in MeCN or EtOH in the presence of HCl at room temperature or under heating did not lead to formation, not even to the appearance of traces of the amide

Synthesis and characterization of 1,2,3,4-naphthalene and anthracene diimides

• Adam D. Bass,
• Daniela Castellanos,
• Xavier A. Calicdan and
• Dennis D. Cao

Beilstein J. Org. Chem. 2024, 20, 1767–1772, doi:10.3762/bjoc.20.155

• . Heating 5 with hexylamine or aniline in refluxing acetic acid successfully led to the formation of the targeted aromatic diimides bearing either N-hexyl (7-Hex) or N-phenyl (7-Ph) substitutions in good yields. The same strategy was employed to create the imide-capped anthracenes 8-Hex and 8-Ph

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• 140a,b (α/β 35:65), which were successfully separated. The following aminolysis of the isolated compounds was achieved by microwave heating using 3 equivalents of butylamine in ethanol at 180 °C. Finally, formation of morpholinones 142 and 143 was accomplished by N-acylation of the corresponding amino

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• exchanged with the hydroxy group of the NHI [21]. No such ion was measured in the mixture before heating. This ion therefore indicates an I–Cl bond in the activated iodane. Starting from I-OH, in a potential path a) formation of hypochlorous acid is suggested, which consequently oxidizes the alcohol through

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• heating. Flash column chromatography was performed using Macherey-Nagel silica gel 60 (230–400 mesh). Deuterated solvents were purchased from Cambridge Isotope Laboratories. UV–vis spectroscopy UV–vis measurements were performed on an Agilent Cary 60 UV–vis spectrophotometer with a quartz cuvette of 1 cm