Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• suitable surrogate. Not only that, the use of safer to use surrogates, is important for use in enabling technologies, like continuous flow and microwave-heated reactions. In fact, CO-free aminocarbonylation reactions are well known, and molybdenum hexacarbonyl (Mo(CO)6) is a very useful surrogate having

Optimizing reaction conditions for the light-driven hydrogen evolution in a loop photoreactor

• Pengcheng Li,
• Daniel Kowalczyk,
• Johannes Liessem,
• Mohamed M. Elnagar,
• Dariusz Mitoraj,
• Radim Beranek and
• Dirk Ziegenbalg

Beilstein J. Org. Chem. 2024, 20, 74–91, doi:10.3762/bjoc.20.9

• evolution using a Pt-loaded polymeric carbon nitride photocatalyst under 365 nm irradiation in the presence of sacrificial reducing agents. The fluid flow pattern of the developed photoreactor was characterized experimentally and the photon flux incident to the loop photoreactor was measured by chemical

• actinometry. The system displayed exceptional stability, with operation sustained over 70 hours. A design of experiment (DOE) analysis was used to systematically investigate the influence of key parameters – photon flux, photocatalyst loading, stirring speed, and inert gas flow rate – on the hydrogen

• generation rate. Linear relationships were found between hydrogen evolution rate and photon flux as well as inert gas flow rate. Photocatalyst loading and stirring speed also showed linear correlations, but could not be correctly described by DOE analysis. Instead, linear single parameter correlations could

Preparing a liquid crystalline dispersion of carbon nanotubes with high aspect ratio

• Keiko Kojima,
• Nodoka Kosugi,
• Hirokuni Jintoku,
• Kazufumi Kobashi and
• Toshiya Okazaki

Beilstein J. Org. Chem. 2024, 20, 52–58, doi:10.3762/bjoc.20.7

• film thickness was analyzed by laser confocal microscopy (Figure 5a, Table 1). The average thickness was ≈393 nm, whereas the edge of the film was much thicker (≈999 nm). In earlier studies, the CNTs in the dispersions were observed to flow and accumulate along the droplet's edge due to the coffee ring

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• [90][91]. Due to their wide electrochemical window, imidazolium ILs are commonly used in organic electrochemistry, simultaneously as solvents and supporting electrolytes [92][93][94]. In addition, the cathodic reduction (both in batch [95] and in flow [96]) can be exploited for the generation of N

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• (Figure 9B). With increasing positive voltage applied, conversion increased in a pseudo-linear manner. At 6 V, the conversion after one passage through the system at a flow rate Qv = 25 µL min–1 increased to 31%. The emergence of conversion in response to applied voltage was consistent with operational

• flow of electrons during a reaction are much larger than the voltage needed to turn-on electron transfer and redox chemistry. This dilemma is overcome by carbon allotropes. They translate voltages weak enough to avoid electron transfer into oriented local molecular macrodipoles that are strong enough

Controlling the reactivity of La@C₈₂ by reduction: reaction of the La@C₈₂ anion with alkyl halide with high regioselectivity

• Yutaka Maeda,
• Saeka Akita,
• Mitsuaki Suzuki,
• Michio Yamada,
• Takeshi Akasaka,
• Kaoru Kobayashi and
• Shigeru Nagase

Beilstein J. Org. Chem. 2023, 19, 1858–1866, doi:10.3762/bjoc.19.138

• ; MALDI–TOF MS (m/z): [MH]+ calcd for LaC89H7, 1214.97; found, 1214.98. Changes in absorption spectra during the reaction of La@C2v-C82 anion with 1a. HPLC profiles of the reaction mixture. Conditions: Buckyprep column (⌀ = 4.6 × 250 mm); eluent, toluene; flow rate, 1 mL/min; UV detector, 330 nm. (a) La

• treated with dichloroacetic acid before injection. HPLC profiles (Buckyprep column (⌀ = 4.6 × 250 mm); eluent, toluene; flow rate, 1.0 mL/min; UV detector, 330 nm.) and MALDI–TOF mass spectra (matrix: dithranol, positive mode) of 2a–5a. Absorption spectra of 2, 3, 4, and 5 in CS2 and absorption spectra of

Thienothiophene-based organic light-emitting diode: synthesis, photophysical properties and application

• Recep Isci and
• Turan Ozturk

Beilstein J. Org. Chem. 2023, 19, 1849–1857, doi:10.3762/bjoc.19.137

• nitrogen flow. Materials 3-Bromothiophene (97%, Across), 2-bromo-4′-methoxyacetophenone (97% Merck), N-bromosuccinimide (Sigma-Aldrich), polyphosphoric acid (PPA, 115% H3PO4 basis, Sigma-Aldrich), n-butyllithium (2.5 M in hexanes, Sigma-Aldrich), sodium sulfate (Merck), 4-bromotriphenylamine (Sigma-Aldrich

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

• flow systems. Accordingly, the main recycling methods rely on the immobilization of catalysts on heterogeneous supports, however, this could often lead to the deterioration of activity and/or selectivity [27]. A possible solution to avoid these drawbacks is the heterogenization of the catalyst after a

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups

• Dayanne Martins,
• Roberta Lamosa,
• Talis Uelisson da Silva,
• Carolina B. P. Ligiero,
• Sérgio de Paula Machado,
• Daphne S. Cukierman and
• Nicolás A. Rey

Beilstein J. Org. Chem. 2023, 19, 1713–1727, doi:10.3762/bjoc.19.125

• of the solid samples in spectroscopic grade potassium bromide (KBr). Thermogravimetric analyses were performed using a Pyris 1 TGA thermoanalyzer (Perkin-Elmer), at 10 °C min−1 heating rate, under nitrogen flow (20 mL min−1), from 25 to 350 °C. Melting points were determined in triplicate using a

A deep-red fluorophore based on naphthothiadiazole as emitter with hybridized local and charge transfer and ambipolar transporting properties for electroluminescent devices

• Suangsiri Arunlimsawat,
• Patteera Funchien,
• Pongsakorn Chasing,
• Atthapon Saenubol,
• Taweesak Sudyoadsuk and
• Vinich Promarak

Beilstein J. Org. Chem. 2023, 19, 1664–1676, doi:10.3762/bjoc.19.122

• illumination). a) DSC and TGA thermograms measured at a heating rate of 10 °C min−1 under N2 flow. b) Cyclic voltammogram (CV) and differential pulse voltammogram (DPV) analyzed in dry CH2Cl2 at a scan rate of 50 mV s−1 under an argon atmosphere (insert: HOMO/HOMO−1/LUMO orbitals). a) Schematic structure of

Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect

• Ken-ichi Nakashima,
• Naohito Abe,
• Masayoshi Oyama,
• Hiroko Murata and
• Makoto Inoue

Beilstein J. Org. Chem. 2023, 19, 1604–1614, doi:10.3762/bjoc.19.117

• filtered and analyzed by HPLC without dilution. HPLC separation was performed on a 150 × 4.6 mm i.d. CAPCELL PAK C18 UG120 column (Osaka Soda) at 35 °C with isocratic elution using 20% CH3CN in 50 mM H3PO4 for 30 min and subsequent column washing with 90% CH3CN at a flow rate 0.8 mL/min. Detection at 250

C–H bond functionalization: recent discoveries and future directions

• Indranil Chatterjee

Beilstein J. Org. Chem. 2023, 19, 1568–1569, doi:10.3762/bjoc.19.114

• techniques. Some energy-economic reactors such as ball mill, microwave, ultrasound and, most importantly, flow reactors have also evolved towards a more sustainable future. To showcase the modern approaches in this domain, this thematic issue in the Beilstein Journal of Organic Chemistry gathers recent

Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis

• Bel Youssouf G. Mountessou,
• Élodie Gisèle M. Anoumedem,
• Blondelle M. Kemkuignou,
• Yasmina Marin-Felix,
• Frank Surup,
• Marc Stadler and
• Simeon F. Kouam

Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112

• % B in 19.5 min and then maintaining 100% B for 5 min, flow rate 0.6 mL/min, UV–vis detection 200–640 nm) connected to a MaXis ESI-TOF mass spectrometer (Bruker) (scan range 100–2500 m/z, capillary voltage 4500 V, dry temperature 200 °C). NMR spectra were recorded at 25 °C on a Bruker (Billerica, MA

• with CH2Cl2/MeOH 97.5:2.5 (v/v) was subjected to a flash chromatography system (PLC 2020, Gilson) equipped with a VP Nucleodur C18 HTec column (10 µm, 250 × 40 mm). The chromatographic separation was performed by using a constant flow rate of 10 mL/min with the mobile phases made with solvent A

• the stationary phase and the solvent mixture CH2CH2/MeOH 92:8 (v/v) as the mobile phase. The elution was performed for 25 min each with a flow rate of 2 mL/min, an automatic pressure in the range of 1–10 bar and the UV absorptions were set at 210, 254, and 366 nm to yield compounds 15 (3.2 mg, yellow

Organic thermally activated delayed fluorescence material with strained benzoguanidine donor

• Alexander C. Brannan,
• Elvie F. P. Beaumont,
• Nguyen Le Phuoc,
• George F. S. Whitehead,
• Mikko Linnolahti and
• Alexander S. Romanov

Beilstein J. Org. Chem. 2023, 19, 1289–1298, doi:10.3762/bjoc.19.95

• , equipped with an AFC-11 4-circle kappa goniometer, VariMAXTM microfocus optics, a Hypix-6000HE detector and an Oxford Cryosystems 800 plus nitrogen flow gas system, at a temperature of 100 K. Data were collected and reduced using CrysAlisPro v42 [21][22]. Absorption correction was performed using empirical

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• . Further, we demonstrated that diazidation could be rendered catalytic using Fe(III) nitrate hydrate III as the iron source and performing the reaction under continuous flow conditions. Interestingly, this mechanism bears some similarity to Lin’s electrocatalytic diazidation, where azido radical generation

• is required for this process, implicating the nitrate counterion functioning as an internal oxidant to regenerate the active Fe(III) species capable of LMCT and RLT. This result is consistent with our finding that iron nitrate can catalytically diazidate alkenes in flow with no additional oxidant and

Enabling artificial photosynthesis systems with molecular recycling: A review of photo- and electrochemical methods for regenerating organic sacrificial electron donors

• Grace A. Lowe

Beilstein J. Org. Chem. 2023, 19, 1198–1215, doi:10.3762/bjoc.19.88

• highlights photo- and electrochemical methods for recycling amines and NADH analogues that can be used as electron donors in artificial photosynthesis. Important properties of sacrificial donors and recycling strategies are also discussed. Compounds from other fields, such as redox flow batteries and

• sacrificial donor. However, it is likely that high steady-state concentrations of a donor will be needed and using the costs targets set for redox flow battery electrolytes is probably a sensible starting point. In an ideal system, the only inputs needed would be carbon dioxide, water, and light. This implies

• sources. Following the example of ‘decoupled water splitting’ and redox flow batteries (RFBs) by recycling the electron donor ex-situ offers several potential advantages [8][57][58]. For example, decoupling carbon dioxide reduction and water oxidation in two separate reactors would allow the development

Two new lanostanoid glycosides isolated from a Kenyan polypore Fomitopsis carnea

• Winnie Chemutai Sum,
• Sherif S. Ebada,
• Didsanutda Gonkhom,
• Cony Decock,
• Rémy Bertrand Teponno,
• Josphat Clement Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2023, 19, 1161–1169, doi:10.3762/bjoc.19.84

• , Milford, MA, USA). The solvent system was as follows; deionized H2O + 0.1% formic acid (FA, v/v) (solvent A) and acetonitrile (ACN) + 0.1% FA (v/v) (solvent B). The separation gradient was operated as follows; 5% B for 0.5 min, 5% B to 100% B for 20 min, and 100% B for 10 min. The flow rate was maintained

• min, 5% B to 100% B within 19.5 min and at 100% B for 5 min. The flow rate was maintained at 0.6 mL/min and UV–vis detection made at 200–600 nm. The calculation of the compounds’ molecular formulas was performed using the Smart Formula algorithm of the Compass DataAnalysis software (Bruker Daltonics

• were performed as follows: isocratic conditions at 5% solvent B for 10 min, followed by an increase to 20% in 3 min, 20% to 90% within 50 min, 90% to 100% in 5 min and finally isocratic conditions of solvent B at 100% for 30 min. The flow rate in each case was 40 mL/min and UV detections were carried

Selective and scalable oxygenation of heteroatoms using the elements of nature: air, water, and light

• Damiano Diprima,
• Hannes Gemoets,
• Stefano Bonciolini and
• Koen Van Aken

Beilstein J. Org. Chem. 2023, 19, 1146–1154, doi:10.3762/bjoc.19.82

• Damiano Diprima Hannes Gemoets Stefano Bonciolini Koen Van Aken Ecosynth, Industrielaan 12, 9800 Deinze, Belgium Flow Chemistry Group, Van ’t Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands Creaflow, Industrielaan 12

• flow using the HANU flow reactor, indicating scalability and improving safety. Keywords: catalyst-free; flow chemistry; oxygen; photochemistry; sustainable oxidation; Introduction Oxidation reactions are widely used in the chemical industry, but are often problematic due to challenges with

• running the process in continuous flow [5][6][7][8]. Moreover, flow reactors that provide intense mixing can overcome the gas–liquid mass transfer limitations typical of batch reactions and improve productivity. Several studies have demonstrated the scalability and safety of such methods for the oxidation

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• feedstocks, and scalability up to gram scales in continuous flow. This review provides comparisons between the two techniques (multi-photon photoredox catalysis and PEC) to help the reader to fully understand their similarities, differences and potential applications and to therefore choose which method is

• standardization but also thanks to developments in technology (flow, alternating polarity) and understanding that fundamentally improve selectivity. Among these is its innovative merger with PRC (synthetic PEC) in a fashion that tackles the issues of both parent techniques and has risen to the forefront of

• efficiency and selectivity of the reactions (vide infra, conPET section). Electrolytes have the potential to be i) aqueous-separated and recovered in batch, or ii) decreased, even ultimately eliminated by flow reactors as an engineering control. Regarding purely the chemical reactivity and scope of

Five new sesquiterpenoids from agarwood of Aquilaria sinensis

• Hong Zhou,
• Xu-Yang Li,
• Hong-Bin Fang,
• He-Zhong Jiang and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 998–1007, doi:10.3762/bjoc.19.75

• purified by preparative HPLC on YMC-Pack-ODS-A with aqueous MeCN (63%), and then purified by semi-preparative HPLC on YMC-Pack-ODS-A with aqueous MeOH (82%) to afford 7 (36.1 mg, tR = 21.3 min; flow rate: 3 mL/min). Fr.6.5 (9.3 g) was further fractionated into ten parts (Fr.6.5.1–Fr.6.5.10) by a silica gel

• min, flow rate: 3 mL/min). Fr.6.5.8 (787.3 mg) was separated by VLC on silica gel eluted with petroleum ether/acetone (25:1–1:1) to provide six portions (Fr.6.5.8.1–Fr.6.5.8.6). Fr.6.5.8.4 (91.0 mg) was further purified by semi-preparative HPLC on SEP Basic 120 C18 with aqueous MeCN (46%) to afford 10

• (4.5 mg, tR = 24.9 min; flow rate: 3 mL/min). Fr.6.6 (9.1 g) was further divided into fifteen parts (Fr.6.6.1–Fr.6.6.15) by a YMC-ODS column (MeOH, 45–80%). Fr.6.6.10 (747.8 g) was separated a by silica gel column washed with petroleum ether/acetone (1:9–6:4) to yield thirteen portions (Fr.6.6.10.1–Fr

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• , Macherey-Nagel) and a gradient of acetonitrile in water supplemented with 0.1% (v/v) trifluoroacetic acid. The gradient conditions were as follows: from 20% acetonitrile to 90% in 30 minutes and kept at 90% for 10 minutes. The flow rate was set to 5 mL/min. The elution of compounds was monitored with a

Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities

• Yuan-Nan Yuan,
• Jin-Qiang Li,
• Hong-Bin Fang,
• Shao-Jun Xing,
• Yong-Ming Yan and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 789–799, doi:10.3762/bjoc.19.59

• /H2O, 70%). Fr. E25 (248.6 mg) was subjected to preparative HPLC (MeOH/H2O (0.04% TFA), 50–100%, flow rate: 10 mL min−1) to obtain six fractions (Fr. E251–Fr. E256). Fr. E254 was concentrated under reduced pressure to yield compound 9 (20.00 mg). Additionally, Fr. E255 (51.8 mg) was further purified

• using semi-preparative HPLC (C30, MeOH/H2O, 25%, flow rate: 3 mL min−1) to yield compound 8 (16.23 mg, tR = 25.04 min). Fr. E5 (9.0 g) was separated into eleven parts (Fr. E51–Fr. E59, Fr. E5A–B) by Sephadex LH-20 (MeOH/H2O, 70%). Fr. E53 (4.26 g) was divided into eleven portions (Fr. E531–Fr. E539, Fr

• :1–1:1), and Fr. E53732 (63.8 mg) was further purified using semi-preparative HPLC (ODS-A, MeCN/H2O (0.04% TFA), 55%, flow rate: 3 mL min−1) to afford compound 7 (15.70 mg, tR = 14.05 min). Fr. E54 (415.3 mg) was separated into twelve fractions (Fr. E541–Fr.E549, Fr. E54A–Fr.E54C) using an MCI gel

Honeycomb reactor: a promising device for streamlining aerobic oxidation under continuous-flow conditions

• Masahiro Hosoya,
• Yusuke Saito and
• Yousuke Horiuchi

Beilstein J. Org. Chem. 2023, 19, 752–763, doi:10.3762/bjoc.19.55

• 10.3762/bjoc.19.55 Abstract We report on the high potential of a honeycomb reactor for the use in aerobic oxidation under continuous-flow conditions. The honeycomb reactor is made of porous material with narrow channels separated by porous walls allowing for high density accumulation in the reactor. This

• structure raised the mixing efficiency of a gas–liquid reaction system, and it effectively accelerated the aerobic oxidation of benzyl alcohols to benzaldehydes under continuous-flow conditions. This reactor is a promising device for streamlining aerobic oxidation with high process safety because it is a

• from operators or the equipment can have disastrous consequences. Because the large headspace of batch reactor aggravates these safety risks, the use of O2 in batch manufacturing is very limited [14]. Recently, continuous flow synthesis has recently been studied as a way to mitigate the safety risks

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• develop a continuous flow process specifically for the C3-alkylation of furfural (Murai reaction). The transposition of a batch process to a continuous flow process is often costly in terms of time and reagents. Therefore, we chose to proceed in two steps: the reaction conditions were first optimized

• using a laboratory-built pulsed-flow system to save reagents. The optimized conditions in this pulsed-flow mode were then successfully transferred to a continuous flow reactor. In addition, the versatility of this continuous flow device allowed both steps of the reaction to be carried out, namely the

• formation of the imine directing group and the C3-functionalization with some vinylsilanes and norbonene. Keywords: biomass; C–H activation; flow; furfural; homogeneous catalysis; Introduction The conversion of biomass derivatives into value-added products is one of the key branches of green chemistry and