Homogeneous continuous flow nitration of O-methylisouronium sulfate and its optimization by kinetic modeling

• Jiapeng Guo,
• Weike Su and
• An Su

Beilstein J. Org. Chem. 2024, 20, 2408–2420, doi:10.3762/bjoc.20.205

• 94%, initial reactant concentration of 0.5 mol/L, reaction temperature of 40 °C, molar ratio of reactants at 4.4:1, and a residence time of 12.36 minutes. Keywords: continuous flow; kinetic modeling; nitration; reaction optimization; static mixer; Introduction The demand for high-quality

• ]. Guo et al. constructed a continuous flow microsystem for o-xylene nitrification and proved the process safety of by the adiabatic temperature rise of the nitrification reaction and the characteristic heat transfer time of the microreactor [9]. The residence time of the microreactor was reduced by an

• ]. The reaction time and temperature were reduced from >2 h and 80 °C in industrial operation to 10 min and 65 °C in the microreactor with high conversion and selectivity. Since O-methylisouronium sulfate can be dissolved in high concentrations of sulfuric acid, it is expected to construct a homogeneous

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• ], screening of reaction conditions for the substrate 1a was carried out. Constant-current electrolysis of 1a using an undivided cell in the presence of carbon dioxide at room temperature was conducted. The effects of the current density (Table 1, entries 1–3), solvent (Table 1, entries 2, 4, and 5

• in less than 10% yield, determined through 1H NMR analysis, except for Table 1, entries 3 (13%) and 5 (25%). It should also be noted that electrolysis was carried out at room temperature, but the temperature of the reaction mixture increased to 40–50 °C at the end of the electrolysis in every case

• of the electroreductive C(sp3)–O bond cleavage, one additional experiment was carried out as shown in Scheme 5. Constant-current electrolysis of 1a in DMSO with 20 mA/cm2 of current density and 6 F/mol of electricity at room temperature under a nitrogen atmosphere instead of carbon dioxide resulted

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• /prooxidant, and antiradical activity was carried out for the catechols synthesized in this work. Results and Discussion Synthesis The interaction of 3,5-di-tert-butyl-o-benzoquinone with the corresponding thiols in ethanol at room temperature under argon leads to the formation of catechol thioethers 1–3 (69

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• reaction temperature (–5 °C). A slightly different protocol was elaborated for N-Fmoc carbamates 54 using the same catalyst 51. Instead of allylsilanes 49, stannanes 55 were employed and the method proved effective in simple allylation, prenylation, and crotylation (57–59). The yields were also generally

• active catalytic species in COBI-catalysed allylations, chemical equilibria in a solution containing catalyst 72, triflic acid, and aldimine 73 were investigated by low-temperature NMR spectroscopy (Scheme 15). Protonation of oxazaborolidine 70 with triflic acid resulted in an 8.3:1 mixture of 71 and 72

• synthesis of homoallylic amines 117 and showed increased yields and enantioselectivities for aromatic aldehydes. In addition, a simple, ambient-temperature hydrolysis procedure was reported that yielded the unprotected analytically pure homoallylic amines in high yields without the need for chromatographic

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

• reagents, solvents and temperature, and the obtained results are summarized in Table 1. Initially, NaNO2 and NOBF4 were chosen as nitrosating reagents in TFA solution. In all cases (Table 1, entries 1–4), the formation of the target product 4 was observed, but the yield did not exceed 33%. Apparently, such

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

• increased equivalents of the linker, elevated temperature, and/or longer reaction time. The limiting factor of this approach might be the size of the target proteins, because for larger proteins it might be more challenging to obtain the desired significant difference between mobility of probe-modified and

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• novel approach based on iminium catalysis employing chiral primary amines under ball milling conditions. Ball milling induces localized and transient temperature and pressure increases which could influence changes in the free activation volume [32][33][34], favoring Michael additions [35]. Furthermore

• nucleophilic catalyst. Test reactions between cyclohexenone and thiomalonate 1 conducted in toluene at room temperature indicated the formation of the product with high conversions and efficiencies (Scheme 2). Application of epi-aminoquinine (AQ-1) in combination with 2-fluorobenzoic acid (system A) led to the

• Michael product. We were sincerely interested in shortening the reaction time. This could be achieved by conducting the reaction under conditions of efficient mixing, increasing substrate concentration without solvents, and utilizing transient but repeatable pressure and temperature increases. These

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

• ). Increasing the reaction temperature negatively affected the efficiency of aziridination: Reactions performed at 30 or 50 °C afforded 3a in 50% and 43% yield, respectively (Table 1, entries 5 and 6). Replacing HFIP with 2,2,2-trifluoroethanol (TFE), which is also a commonly encountered fluorinated alcohol

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

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• ) was reacted with the Brønsted acid (X equiv) and the fluorine source (Y equiv) in the solvent (4 mL) at temperature of T (°C) for Z hours. The chemical yield of the desired product, (5,5-difluorohexyl)benzene (2a), was evaluated for reaction optimization by using the 19F nuclear magnetic resonance

• (NMR) yield, in which trifluorotoluene (CF3C6H5) was used as an internal standard. The use of Tf2NH (5 equiv or 10 equiv) and Bu4NBF4 (5 equiv) in CH2Cl2 at room temperature gave the corresponding product 2a in up to 83% yield (Table 1, entries 1–5). The use of CF3COOH did not yield 2a at all (Table 1

• Bu4NBF4 was not effective (Table 1, entries 11 and 12). Finally, investigations of the amount of Bu4NBF4 and the reaction temperature demonstrated that conditions including Bu4NBF4 (9 equiv) and room temperature gave the best result (Table 1, entries 13–17). Based on the above investigation, we decided to

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

• was outside the scope of this study. Next, DBA 5 was subjected to the SpAAC with benzyl azide. When two equivalents of benzyl azide were added to a solution of 5 in CDCl3 at a controlled temperature of 30 °C, the reaction slowly proceeded (Figure 2). After 22 h, the original peak ascribed to starting

• indicates that the formed double azide adduct is 6a, which is consistent with our previous report [18]. The double azide addition was further investigated by changing the reaction temperature. The rate constant was determined by the temperature-dependent 1H NMR spectra in CDCl3. The reaction kinetics

• partially azidated poly(vinyl chloride) (PVA-N3) was prepared by stirring poly(vinyl chloride) and NaN3 in DMF at room temperature overnight. Measurements NMR spectra were recorded using a JEOL mode Al300 (300 MHz) at room temperature. Deuterated chloroform was used as the solvent unless otherwise stated

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

• , 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

• the amount of NaOH on the reaction (Table 1, entries 10–12). The reaction obviously showed dependence on the amount of NaOH, and 3a was obtained in 90% yield when the reaction ran for 24 h in the presence of 3.0 equiv of NaOH (Table 1, entry 11). However, when lowering the reaction temperature to 90

• , entries 11 and 14), while the reaction afforded 3a in low yield in the presence of weak bases such as Na2CO3 and Et3N (Table 1, entries 15 and 16). Accordingly, the optimal reaction conditions for the synthesis of 3a were 3.0 equiv of NaOH as catalyst and reflux temperature (conditions B). With the

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

• , but its effective realization is limited by the need for both a solvent as well as a supporting electrolyte to allow for the flow of current through the reaction. Although some imaginative options have been reported, they tend to be quite limited in scope. Room temperature ionic liquids (RTILs) were

• solvents Tetrabutylammonium bromide/ethylene glycol (1:3 molar ratio) deep eutectic solvent To 8.0 grams of tetrabutylammonium bromide (TBAB) were added 4.7 grams of ethylene glycol (EG). The resulting mixture was heated to 70 °C until a homogeneous liquid formed. It was stored at this same temperature

• between uses. Choline chloride/ethylene glycol (1:2 molar ratio) deep eutectic solvent To 6.98 grams of choline chloride (CC) were added 6.2 grams of EG and the resulting mixture was heated to 70 °C until a homogeneous liquid formed. It was stored at this same temperature between uses. General Sn/Sn

Novel truxene-based dipyrromethanes (DPMs): synthesis, spectroscopic characterization and photophysical properties

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2024, 20, 2163–2170, doi:10.3762/bjoc.20.186

• –80%) along with their preliminary photophysical (absorption, emission and time resolved fluorescence lifetime) properties. The condensation reaction for assembling the required DPMs were catalyzed with trifluoroacetic acid (TFA) at 0 °C to room temperature (rt), and the stable dipyrromethanes were

• atmosphere. The flask was cooled to 0 ºC, and stirred vigorously after that n-BuBr (11.30 mL, 105.12 mmol) was slowly added to the RB-flask, and the mixture was stirred for 24 h at room temperature (rt), until the reaction completed (TLC monitoring). Then the reaction mixture was quenched with water, and the

• different equivalents (2 equiv for 12, 6 equiv for 15 and 9 equiv for 17) at 0 °C under N2 atmosphere. The red reaction mixture was stirred for 30 min at 0 °C, and further stirred at room temperature for 1 to 6 hours. After the reaction completion (TLC monitoring), the mixture was poured gradually into

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

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

• pore channels that are distant from the pore openings are unlikely to be accessible to the catalyst [72]. Ionic bonding is a straightforward and economical immobilisation method. This form of non-covalent immobilisation can be reversed by altering the temperature and ionic strength [71]. Furthermore

• % increase in yields, however, further increase in pressure proved to be non-beneficial. Moreover, increasing the temperature provided higher yields at optimised pressure (60 bar) but also led to lowered enantioselectivity (Scheme 7) [121]. Zhang and co-workers prepared a novel polymer with an ordered

• mesoporous material. Photoinduced RAFT polymerisation of n-butyl acrylate (19) catalysed by silica nanoparticle-supported eosin Y 21, which could be recycled over five reaction cycles. Pressure and temperature dependence of the 1,4-addition of propanal to trans-β-nitrostyrene under continuous flow conditions

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

• conditions, a significant amount of degradation products was observed and the yield was rather low. The same result was obtained when the reagent was first added at 0 °C and then heated for one hour under microwave irradiation (Table 1, entry 2). To avoid degradation, the temperature was reduced while the

• decided to use 2 equivalents of DIPEA at low temperature. After ten minutes at −15 °C to allow for the reaction between phenyl trifluoromethyl sulfoxide (1a) and acetonitrile, the base was added and the reaction was stirred for the same amount of time. To our delight, a good NMR yield of 74% was received

• under these conditions (Table 1, entry 4). The importance of the temperature was then evaluated (Table 1, entries 5–7). A too low value was deleterious to the yield, whereas −5 °C appeared as the conditions of choice. Finally, by adjusting to 5 equivalents of nitrile and base, resulted in the optimal

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

• , which was monitored through the disappearance of isocyanide in the reaction medium using a color reaction [19]. Then the emulsion was applied to the glass surface and evaporated at a temperature of 50 °C. The resulting samples were analyzed using fluorescence microscopy at a wavelength of 490 nm. After

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• from curcumins and arylidenemalonates is reported. This strategy works in the presence of aqueous KOH using TBAB as a suitable phase transfer catalyst at room temperature. The functionalized cyclohexanones are formed as major products in moderate to excellent yields with complete diastereoselectivity

• base (KOH) and a phase-transfer catalyst (PTC) in a biphasic medium (toluene–H2O) at room temperature, leading to highly functionalized cyclohexanones and tetrahydrochromenones as major and minor products, respectively, in moderate to high yield and excellent diastereoselectivity. Results and

• Discussion Initially, the reaction of 1a with 2a was carried out with 3.0 equiv of aq KOH as base and toluene as a solvent in the presence of 20 mol % tetrabutylammonium bromide (TBAB) as a phase-transfer catalyst at room temperature for 24 h (Table 1, entry 1). To our delight, the formation of double

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

• ]. In addition to this, AAPTAB has a high thermal half-life at room temperature (5.7 years [19]), meaning there is no significant contribution from thermal Z–E isomerisation over the course of these experiments. Using in-situ UV- and visible-light irradiation with SAXS, here we measure the intermediate

• to the AzoTAB, as seen in similar amphiphilic systems [30][31]. In the case of ionisation, both stereoisomers would be expected to be affected equally. In comparison to Azo, the AAP moiety is much more stable as the Z isomer, with a thermal half-life of 5.7 years at room temperature [13]. This means

• the temperature change due to heating effects from the X-ray beam is <0.4 °C for a single 500 ms frame (see section 7, Supporting Information File 1), meaning that this will not affect the Z–E isomer ratio. The diverse range of reactive radical species formed in the radiolysis process must therefore

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

• ) [43]. In parallel, Sheng and Zhang et al. found that 2-(1,3,4-oxadiazol-2-yl)aniline derivatives 38 could be electrochemically synthesized from isatins 35 and acylhydrazine 36. The transformation was carried out in an undivided cell at high temperature in DMSO using potassium iodide as supporting

• NH-tosylhydrazones 89 for the electrochemical construction of 1,2,3-thiadiazoles 91. The electrolysis was conducted in an undivided cell at high temperature using ammonium iodide as electrocatalyst. Interestingly, no additional electrolyte was required. The transformation accommodated various

• reaction conditions. For instance, the use of lithium perchlorate as supporting electrolyte in acetonitrile at room temperature in a divided cell equipped with two platinum electrodes led exclusively to diazines 131 in good yields. In contrast, when the electrolysis was conducted in methanol containing

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• , 332.1832; found, 332.1838. Methylation of 1 Allostreptopyrrole A (1, 2.0 mg, 0.007 mmol) and K2CO3 (4.4 mg, 0.032 mmol) were stirred in dry DMF (0.5 mL) at 50 °C for 10 min. Methyl iodide (19 μL, 0.32 mmol) was added and the mixture was stirred at this temperature for 12 h [29]. Reaction completion was

Development of a flow photochemical process for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence: in situ-generated 2-benzopyrylium as photoredox catalyst and reactive intermediate

• Masahiro Terada,
• Zen Iwasaki,
• Ryohei Yazaki,
• Shigenobu Umemiya and
• Jun Kikuchi

Beilstein J. Org. Chem. 2024, 20, 1973–1980, doi:10.3762/bjoc.20.173

• scale-up, are the advantages of using a flow system. In addition, reproducibility in a liquid–liquid flow system is improved because the flow velocity and temperature can be precisely controlled by using a syringe pump and a temperature control unit, respectively. Moreover, as the reaction mixture

• moderate yield (entry 1: 42%, cf. batch reaction: 76%). Lowering the reaction temperature to 25 °C reduced the yield (Table 1, entry 2: 35%), but decreasing the amount of the phosphine ligand from 20 mol % to 5 mol % markedly improved the yield (Table 1, entry 3: 53%). Even when the flow rate was increased

• result, extending the premixing time and the light irradiation time (Table 2, entry 2) led to an improved yield; the obtained yield was higher than that of the batch reaction system even when half the amount of AgNTf2 was used with the temperature reduced to 25 °C (flow: 54% vs batch: 48%). Meanwhile

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

• ]. Additionally, when the reaction was performed using DMSO-d6 (or CD3CN) and CH3ONa, H/D exchange occurred already at ambient temperature (25 °C, 20 h) [78]. The formation of CDF=CDF was confirmed by NMR spectroscopy, namely by the change of signal multiplicity in the 19F NMR spectra of E- and Z-isomers of 1,2

• required 2–3 weeks at the same temperature. In this case, sufficient E–Z isomerization of the starting olefin occurred during the reaction, and the major product was 5,6-endo,endo-difluoro-1,2,3,4,7,7-hexachlorobicyclo[2.2.1]-2-heptene, which was formed from (Z)-1,2-difluoroethylene (Scheme 20). Both

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

• -substituted indazole analogs in 44% and 40% yields, respectively, by treating compound 6 with methyl iodide and potassium carbonate in dimethylformamide (DMF) at room temperature for 17 h [40]. Other works have shown poor selectivity when 6 and other isomers similar to 6 were reacted with isopropyl iodide and

• % at room temperature to 89% when warmed to 50 °C. No information was provided to justify any N2-selectivity or the lack thereof. Should an N2–Cs+–O ion pair exist, this could reasonably account for all the reported results presented herein (vide infra). Additionally, using Cs2CO3 in dioxane provided

• no products at room temperature (see Table 1) presumably due to the low solubility of Cs2CO3 in dioxane. They also provided a single example of a Mitsunobu reaction utilizing n-pentanol, dibutyl azodicarboxylate (DBAD), and PPh3. Therefore, there is still a great need to develop an operationally