Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• to that reported in reference [23], to a solution of DEMO (1.72 g, 10.0 mmol) in toluene (40 mL) were added 4-methylbenzamide (1.63 g, 12 mmol), 3 Å molecular sieves (3.4 g), and acetic anhydride (2.0 mL, 20 mmol). The resulting solution was heated at 100 °C for 4 h. After cooling to room temperature

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• in the mass spectra were interpreted on the basis of pre-calculated weights (as molecular ions with [M + H]+) for all possible initial, intermediate, and expected interaction products (Table 1). The tentative experiments showed that when toluene or dioxane were used as solvents, the maximum

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

• sufficient mixing. Silica could not fulfill this role. Lastly, water, 1,4-dioxane, chloroform, and toluene were tested in a liquid-assisted grinding (LAG) protocol (Table 1, entries 10–13). The lowest yields were obtained with water and 1,4-dioxane, providing 3a in yields of 37% and 43%, respectively (Table

•  1, entries 10 and 11). With the less polar solvents chloroform and toluene 3a was obtained in 62% and 68% yield, respectively (Table 1, entries 12 and 13). For comparison, the difluoromethylation of ketone 1a with difluorocarbene precursor TMSCF2Br (2) was investigated in solution (Scheme 2). The

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• with aldehydes 8, 9, and 10 under Lindsey conditions [42] utilizing BF3·OEt2 and DDQ [43] to achieve porphyrins 4, 5, and 6, which were not isolated and instead reacted immediately. Ni(II)porphyrins 11, 12, and 13 were prepared by reacting porphyrins 4, 5, and 6 in toluene for 18 hours using Ni(II

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• Science and Engineering, Ibaraki University, 4-12-1 Nakanarusawa, Hitachi, Ibaraki 316-8511, Japan 10.3762/bjoc.20.233 Abstract Treatment of various (R)-N-(2,2,3,3-tetrafluoropent-4-en-1-ylidene)-1-phenylethylamine derivatives with 2.4 equiv of DBU in toluene at room temperature to 50 °C for 24 h led to

• diethyl ether, toluene, hexane, and cyclohexane, (S)-20b was obtained in 30% to 40% yield and significant amounts of unreacted substrate were still observed, although formation of the byproduct 22b could be generally suppressed. We also examined the reaction using other bases instead of DBU. As shown in

Interaction of a pyrene derivative with cationic [60]fullerene in phospholipid membranes and its effects on photodynamic actions

• Hayato Takagi,
• Çetin Çelik,
• Ryosuke Fukuda,
• Qi Guo,
• Tomohiro Higashino,
• Hiroshi Imahori,
• Yoko Yamakoshi and
• Tatsuya Murakami

Beilstein J. Org. Chem. 2024, 20, 2732–2738, doi:10.3762/bjoc.20.231

• ., Kyoto, Japan) and toluene (FUJIFILM Wako Pure Chemical Corporation, Osaka, Japan). DMPC in ethanol and catC60 or C60 in DMSO/toluene were mixed in molar ratios of 1:0, 1:0.1, 1:1, or 1:10, and the solvent was removed using a rotary evaporator (Rotavapor R-300, BÜCHI Labortechnik AG, Switzerland) at 40

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

• Ruben Manuel Figueira de Abreu,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• -Flight (TOF) LC–MS. The solvent, toluene, was purchased as dry solvent and applied without further purification. Other reagents, catalysts, ligands, acids, and bases were used as purchased from commercial suppliers. Column chromatography was performed on Merck Silica gel 60 (particle size 63–200 μm

• (51), 271 (18), 268 (26); HRESIMS-TOF (m/z): [M + H]+ calcd for C23H19N2O2S, 387.1167; found, 387.1171. General procedure for the preparation of 5 A mixture of the corresponding starting material 4 (0.145 mmol) and p-TsOH·H2O (20 equiv; 2.94 mmol; 559 mg) was dissolved in dry toluene (2 mL) and

• (PPh3)4 (10 mol %), NaOH (3 equiv), 1,4-dioxane/water 5:1, 100 °C, 1 h; iv) p-TsOH (20 equiv), toluene, 100 °C, 4 h. Synthesis and isolated yields of 1,3-dimethyl-5-aryl-6-[2-(aryl)ethynyl]uracils 4a–i. Reaction conditions: 3 (1 equiv), boronic acid (1.2 equiv), Pd(PPh3)4 (5 mol %), NaOH (3 equiv), 1,4

Anion-dependent ion-pairing assemblies of triazatriangulenium cation that interferes with stacking structures

• Yohei Haketa,
• Takuma Matsuda and
• Hiromitsu Maeda

Beilstein J. Org. Chem. 2024, 20, 2567–2576, doi:10.3762/bjoc.20.215

• -heptane for 2+-Cl−, 2+-BF4−, and 2+-PCCp−, CH2Cl2/n-heptane with small amounts of MeOH and toluene for 2+-PF6−, and toluene/n-hexane for 2+-B(C6F5)4− (Figure 3 and Figures S11–15 in Supporting Information File 1) [32]. In the single crystals, 2+ showed highly planar core structures with mean-plane

• amounts of MeOH and toluene. The data crystal was a red prism of approximate dimensions 0.20 mm × 0.02 mm × 0.01 mm. A single crystal of 2+-PCCp− was obtained by vapor diffusion of n-heptane into a CHCl3 solution. The data crystal was a red prism of approximate dimensions 0.050 mm × 0.030 mm × 0.010 mm. A

• single crystal of 2+-B(C6F5)4− was obtained by vapor diffusion of n-hexane into a toluene solution. The data crystal was a red prism of approximate dimensions 0.05 mm × 0.01 mm × 0.01 mm. The data of 2+-Cl− and 2+-BF4− were collected at 90 K on a Bruker D8 Venture diffractometer with Mo Kα radiation (λ

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• ]. Through tailored molecular design, it is possible to enhance the oxidation capability of these catalysts, enabling the utilization of less reactive alkenes and even aromatic molecules such as toluene [32]. Until now, heterocyclic amides such as β-lactam compounds have not been employed in alkene

• starting from succinimide (Scheme 3). Through a simple reaction in toluene at 80 °C in the presence of Zn(OAc)2, the hemiaminal derivative 13 underwent substitution with cinnamyl alcohol, resulting in the isolation of 14 with a satisfactory yield. Under optimized reaction conditions, the photocatalytic

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

• -diaminonaphthalene derivatives 42, which after hydrolysis and extraction into toluene, were reacted with indole, 3-methylindole, 3,4-dihydroisoquinoline, and benzoyl hydrazone ethyl glyoxylate ester to afford terminal (E)-trifluoromethyl homoallylic amines 44 with up to 3 adjacent stereocentres with high to

• equiv of isatin with a 50% excess of the α-CF3-substituted imine in toluene at room temperature in the presence of 10 mol % of organocatalyst 138 for times between 1 and 80 h. The reaction exhibited a broad scope in the isatin carbonate derivatives with high to excellent enantioselectivities (89–99

• catalyses the methylene group transfer, resulting in azonia-[3,3]-sigmatropic rearrangement, followed by regeneration of methylene imine by an elimination step [47]. The reaction proceeded in toluene at 80 °C with 20 mol % of the CPA catalyst 151 over 20 hours resulting in low to moderate

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

• 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

• isolated product. However, the decrease in the enantioselectivity was noted in comparison to the reaction under standard conditions in toluene (93% vs 85% in ball mill). Surprisingly, the essential loss of enantioselectivity was noted when system B was applied in analogous transformation. Although an

• products with 61% and 63% yield in the solution and mixer mill, respectively. However, the drop of stereoselectivity was noted in comparison to the reaction in toluene (94% ee vs 86% ee in mixer mill, ∆ee = 8). It should be noted that the dibenzyl malonate remained inactive for subjecting to reaction under

Synthesis and reactivity of the di(9-anthryl)methyl radical

• Tomohiko Nishiuchi,
• Kazuma Takahashi,
• Yuta Makihara and
• Takashi Kubo

Beilstein J. Org. Chem. 2024, 20, 2254–2260, doi:10.3762/bjoc.20.193

• ESR tube, evaporating it, and then dissolving it in degassed toluene. The ESR spectrum of the DAntM radical displayed two broad signals with g = 2.0028 (Figure 3a). The simulated spectrum indicated that the unpaired electron mainly locates at the central sp2 carbon but is slightly delocalized over the

• rate dependency (0.1, 0.5, 1.0, 2.0, and 3.0 V s−1) of the redox wave. Measurement conditions: 100 mM n-Bu4NPF6 and 1 mM DAntM cation in CH2Cl2. Red arrows indicate the sweep direction. UV–vis–NIR spectra of (a) DAntM radical in toluene, (b) DAntM cation in TFA. Synthetic route to the DAntM radical

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

• . At the first stage, submicron colloidal particles based on carboxymethylcellulose and chitosan with a domain structure were obtained in an aqueous suspension. In the second stage, the Ugi reaction was carried out on the surface of the Pickering emulsions with toluene. Removal of toluene and

• ) [17]. As before, depending on the CMC concentration, we obtained submicron particles with an average diameter from 200–600 nm, which were visible under an optical microscope in the form of luminous points. Next, Pickering emulsions were obtained by emulsifying toluene in an aqueous suspension of

• particles with a concentration of 0.3 g/L and a water/toluene ratio of 3:1. However, it was not possible to distinguish any details on the surface of the droplets using conventional and confocal microscopy (Figure 1). To do this, it was necessary to remove the solvent that interfered with obtaining a

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

• toluene [173]. N-Vinylimidazole, an alkene with a leaving group, was used to synthesize the 3-substituted pyrazoles 169 because, unlike acetylene, it is not gaseous and, therefore, easier to handle. Instead of vinylimidazole, vinyl azides 170 can also be used as alkyne surrogates. After the 1,3-dipolar

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

• 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

• Michael addition product 3a was observed in 31% yield. The reaction with 6.0 equiv of KOH resulted in an increase in the yield of 3a (72%) and also the formation of 4a in low yield (13%, Table 1, entry 2). Next, the THF–toluene solvent system was employed in the absence and presence of TBAB, affording 3a

Radical reactivity of antiaromatic Ni(II) norcorroles with azo radical initiators

• Siham Asyiqin Shafie,
• Ryo Nozawa,
• Hideaki Takano and
• Hiroshi Shinokubo

Beilstein J. Org. Chem. 2024, 20, 1967–1972, doi:10.3762/bjoc.20.172

• toluene (Scheme 1). The reaction smoothly proceeded to afford dialkylated macrocycle 2a in 92% yield. In addition to 2a, monoalkylated product 3a and dipyrrin dimer 4a were obtained as minor products in 4% and 3% yield, respectively. The structure of 2a was unambiguously confirmed by single-crystal X-ray

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

• that time, along with some 30 solvents. The most widely used conditions, however, remained those originally discovered by Groebke, Blackburn and Bienaymé, namely the use of Sc(OTf)3, perchloric acid or p-toluenesulfonic acid as catalysts, and methanol, ethanol or toluene as solvents, or under solvent

• composite compared to the individual constituents tested separately. Solvent-free conditions afforded better yields than traditional solvents (water, toluene, DCM, EtOH, MeOH) and 12 adducts were synthetized in 84–96% yield. Finally, the catalyst was recycled six times with a slight decrease in efficiency

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

• studies of chiral bifunctional sulfide-catalyzed bromolactonizations [26][27][28][29][30][31], mixed solvent systems were investigated. Among the examined solvent systems, a dichloromethane/toluene mixed solvent (3:1 ration) showed the best enantioselectivity (89:11 er). With the optimal catalyst (S)-1g

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

• fluorinate PhMgBr as reported with iodine(V) fluoride 3 by Amey and Martin [21]. Difluoroiodane 6 was first reacted with phenylmagnesium chloride in dry toluene at 0 °C, but fluorobenzene was not formed under these reaction conditions. The reaction was then repeated using phenylmagnesium bromide, but

• afford iodoalcohol 14 in 93% yield. In the final step iodoalcohol 14 underwent an oxidative fluorination with Selectfluor at room temperature to deliver methyl(trifluoromethyl)fluoroiodane 15 in a good 68% yield after recrystallisation from toluene. Although bis(trifluoromethyl)fluoroiodane 19 has been

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• short distance between the electrodes, and easily reproduceable conditions. The electrochemical oxidation of phenols has been performed with platinum anodes [37][41], and carbon/platinum worked well for the oxidation of toluene dissolved in methanol with tetraethylammonium tosylate (Et4NOTs) as a

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

• -oxathiaphospholane steroids In 2012, Krstić et al. reported the synthesis of spiro-1,3,2-oxathiaphospholane steroids using Lawesson’s reagent (LR) as a thionating and phosphorylating agent in the reaction with 17α-hydroxyprogesterone (107) [58]. The reaction was conducted in toluene, dichloromethane, or carbon

• -1,3,2-oxathiaphospholane (109) was obtained under all conditions. However, when the reaction time was increased to 5 h in toluene, no 108 was detected, but a higher yield of 109 was produced. The best yield (46%) for 109 was achieved after 7 hours of refluxing dichloromethane. Both compounds were

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• intermediate is then reduced with H2 [37]. When synthesising via a reductive ring opening, typically, an N-Fmoc-protected amino acid is condensed with formaldehyde in the presence of p-toluic acid in refluxing toluene to yield the 5-oxazolidinone. Reductive ring opening can be achieved by using an excess of

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• alcohol, isopropyl alcohol, and toluene) increased the reactivity of MtCh509 relative to the aqueous system, representing the first solvent‑tolerant chitinase from Microbulbifer species and its potential applications in industrial processes [50]. rChi1602 exhibited maximal activity at 60 °C and over a

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• phosphonation of the aldehyde group. To implement this strategy, a reaction between 4-hydroxybenzaldehyde (12) and cyanuric chloride (1) was performed, in toluene with Na2CO3 as base, to obtain compound 19 [58] in very good yield (87%) (Scheme 7). Compound 19 was subjected to similar reaction conditions that

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• preliminary electrochemical examples [93][101]. Middleton and co-workers described an alternating polarity approach for the fluorination of simple toluene derivatives in neat pyridine·HF (Figure 42) [102][103]. Poor conductivity necessitated the use of this waveform type. The benzylic fluorination was

• toluene derivatives. Ring fluorination–migration product yields in parentheses. Electrochemical primary benzylic C(sp3)–H fluorination utilizing pulsed current electrolysis. Acknowledgements We would like to acknowledge Dr Joseph Tate (Syngenta) for discussions. Funding We would like to thank the Royal