Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• ratios of 74.1% in TNF-α and 64.1% in CCL2 at a concentration of 1 μM (Figure 6). Conclusion The continuous chemical investigation of the sponge A. cavernosa has resulted in the isolation of nine non-nitrogenous sesquiterpenoids, of which four optically pure compounds [(+)-1, (+)-4, (+)-5, and (−)-5] are

Continuous flow synthesis of azobenzenes via Baeyer–Mills reaction

• Jan H. Griwatz,
• Anne Kunz and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2022, 18, 781–787, doi:10.3762/bjoc.18.78

• used Baeyer–Mills coupling reaction was adopted to a continuous flow setup. The versatility was demonstrated with a scope of 20 substances and the scalability of this method exemplified by the synthesis of >70 g of an azobenzene derivative applied in molecular solar thermal storage (MOST) systems

• . Keywords: azobenzenes; Baeyer–Mills reaction; continuous flow; molecular switches; solar fuel; Introduction Although the red-colored azobenzenes (AB) have been known for years as dyes, their applications nowadays span from energy and information storage [1][2][3][4][5], organocatalysis [6], photobiology

• the proposed mechanism, which involves nucleophilic attack of the aniline on the nitrosobenzene derivatives in acidic or basic media (Scheme 1) [18][19][20][21]. However, in order to use azobenzenes as functional materials, access to a large-scale process is necessary. In this context continuous flow

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• , Germany 10.3762/bjoc.18.76 Abstract Continuous flow technology is a key technology for sustainable manufacturing with numerous applications for the synthesis of fine chemicals. In recent years, the preparation of odorants utilizing the advantages of flow reactors received growing attention. In this

• toroidal currents occur within the liquid slugs which result in a continuous mixing of the liquid slugs. Therefore, the reaction proceeds up to 100 times faster in flow than under conventional batch conditions [25]. Although, pure isoamyl acetate (10) has a “pronounced, fruity-fresh odor” which is

• “has a pleasant, fresh-citrusy, and peppery-woody odor with a discretely mint note” [9]. Very recently, Kobayashi, Ishitani, and co-workers described a three-step sequential continuous flow process for the synthesis of (S)-α-phellandrene (30) from (R)-carvone (25, Scheme 6) [36]. In the first step, a

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• is important not only in the context of energy storage, CO2 reduction, and climate change prevention, but also because they provide a country-independent source of energy. However, for use in a continuous flow system, the catalyst must have extremely high SAR and catalytic activity. Recently, a

• mesoflow technology and indirect heating 3.1 Microwave-accelerated reactions under flow conditions Reactions that take 20 minutes or longer under classical batch conditions can be accelerated considerably under continuous flow conditions by rapid heating, because flow chemistry usually involves the use of

• dioxide (core-shell nanostructured particles), called MagSilicaTM to be used as fixed-bed materials in many different continuous flow processes (Figure 4A) [50]. These materials are excited very rapidly in a medium frequency (25 kHz) electromagnetic field, heating reaction mixtures in packed bed reactors

Rapid gas–liquid reaction in flow. Continuous synthesis and production of cyclohexene oxide

• Kyoko Mandai,
• Tetsuya Yamamoto,
• Hiroki Mandai and
• Aiichiro Nagaki

Beilstein J. Org. Chem. 2022, 18, 660–668, doi:10.3762/bjoc.18.67

• Medical Science, Nijigaoka, Kani-city, Gifu Prefecture, 509-0293, Japan 10.3762/bjoc.18.67 Abstract The enhanced reaction rate in the epoxidation of cyclohexene with air as an oxidant was discovered without any added catalyst utilizing a continuous flow reactor constructed with readily available

• stainless steel parts and devices. This continuous-flow process demonstrates a significant improvement in reaction time for highly selective epoxide production over the batch process due to the efficient mass transfer between the liquid phase and air. The flow process discovered was operated continuously

• with good operational stability, evaluated by a constant high yield of cyclohexene oxide, to obtain the desired product with high productivity. Keywords: air; continuous flow; cyclohexene oxide; flow epoxidation; rapid gas–liquid reaction; Introduction From the past to the present, organic synthesis

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• of the cage/architecture depends on its dynamics: the catalytic activity will correlate with the rate of thermal motion. As illustrated below, there are presently two phenomena known where continuous nanomechanical motion influences the catalytic activity: a) Increasing nanomechanical speed reduces

Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid

• Jannis A. Reich,
• Miriam Aßmann,
• Kristin Hölting,
• Paul Bubenheim,
• Jürgen Kuballa and
• Andreas Liese

Beilstein J. Org. Chem. 2022, 18, 567–579, doi:10.3762/bjoc.18.59

• Abstract The importance of a compound that helps fight against influenza is, in times of a pandemic, self-evident. In order to produce these compounds in vast quantities, many researchers consider continuous flow reactors in chemical industry as next stepping stone for large scale production. For these

• reasons, the synthesis of N-acetylneuraminic acid (Neu5Ac) in a continuous fixed-bed reactor by an immobilized epimerase and aldolase was investigated in detail. The immobilized enzymes showed high stability, with half-life times > 173 days under storage conditions (6 °C in buffer) and reusability over 50

• recycling steps, and were characterized regarding the reaction kinetics (initial rate) and scalability (different lab scales) in a batch reactor. The reaction kinetics were studied in a continuous flow reactor. A high-pressure circular reactor (up to 130 MPa) was applied for the investigation of changes in

Synthesis of piperidine and pyrrolidine derivatives by electroreductive cyclization of imine with terminal dihaloalkanes in a flow microreactor

• Yuki Naito,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 350–359, doi:10.3762/bjoc.18.39

• . Furthermore, piperidine and pyrrolidine derivatives could be obtained on preparative scale by continuous electrolysis for approximately 1 hour. Keywords: electrochemical synthesis; electrocyclization; flow microreactor; heterocyclic amines; imine; Introduction Heterocycles are a very important class of

• determined (Figure 3). Continuous flow electrolysis could be performed without any problem at least until the fifth fraction collection. The yields of the fractions were almost the same, and the average yield of the five fractions was 77%. In addition, no precipitates were observed on the electrodes after

• approximately 1 hour of continuous electrolysis; therefore, we then attempted to synthesize pyrrolidine and azetidine derivatives (3b and 3c) using the same procedure (entries 2 and 3 of Table 8). 3b was obtained from imine 1 and dihaloalkane 2d with a good isolated yield (57%, 75.8 mg). However, the azetidine

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• Kian Donnelly Marcus Baumann School of Chemistry, University College Dublin, Science Centre South, Belfield, Dublin 4, Ireland 10.3762/bjoc.18.27 Abstract An efficient continuous flow process is reported for the synthesis of various 1,3,4-oxadiazoles via an iodine-mediated oxidative cyclisation

• the ability to improve reaction efficiency, safety and provide access to chemistry that was not previously possible [9][10][11]. Carrying out a reaction in continuous flow mode can improve its efficiency in several ways, including decreasing reaction times, increasing yields, or eliminating tedious

• significant development in continuous flow platforms, particularly in industry [16][17][18][19][20]. 1,3,4-Oxadiazoles are biologically relevant 5-membered heterocyclic compounds with various favourable pharmacokinetic properties and have been investigated as potential candidates for antiviral, antifungal and

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• and purity (qualitative assessment based on the NMR analysis) without further purification. Enzyme inhibition assays The inhibitory activities of compounds 3a–h toward TcTS and neuraminidase were assessed by a continuous fluorimetric assay [34], which is based on the residual hydrolase activity of

• ) with 20 mM HEPES, pH 7.5, 150 mM NaCl, 1 mL/min. Fractions containing TcTS were pooled and concentrated using Amicon Ultra-15 Centrifugal Filter (30,000 MW cut off) [42]. TcTS and neuraminidase inhibition assays Inhibition of both enzymes was assessed based on the continuous fluorimetric assay

High-speed C–H chlorination of ethylene carbonate using a new photoflow setup

• Takayoshi Kasakado,
• Takahide Fukuyama,
• Tomohiro Nakagawa,
• Shinji Taguchi and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2022, 18, 152–158, doi:10.3762/bjoc.18.16

• the reaction and the system should be kept dry for continuous production. We are now investigating some other photo gas–liquid flow reactions, which will be reported in due course. Experimental The photoflow setup consisting of a flow photoreactor LX-1 and UV-LEDs were supplied from MiChS Inc., Ltd

Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions

• Soumyadip Basu,
• Sauvik Chatterjee,
• Suman Ray,
• Suvendu Maity,
• Prasanta Ghosh,
• Asim Bhaumik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14

• under continuous stirring to a suspension of chitosan (5 g) in 100 mL of water. An ammonia solution was used to adjust the pH value of the mixture to 9. The solution was further stirred continuously overnight at room temperature. After that, the green catalyst was separated by filtration and dried under

Chemoselective N-acylation of indoles using thioesters as acyl source

• Tianri Du,
• Xiangmu Wei,
• Honghong Xu,
• Xin Zhang,
• Ruiru Fang,
• Zheng Yuan,
• Zhi Liang and
• Yahui Li

Beilstein J. Org. Chem. 2022, 18, 89–94, doi:10.3762/bjoc.18.9

• continuous interest on thioesters, herein, we report an efficient and chemoselective protocol for the synthesis of indoleamide derivatives with thioesters as acyl source. Results and Discussion At the beginning of our studies, we selected 3-methyl-1H-indole (1a) and S-methyl butanethioate (2a) as the model

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• addition, several authors concluded that this was a good method for analytically determining low levels of activated aromatic amines in drugs. This method continued to be used over the years and was subsequently optimized by a spectrophotometric determination technique coupled with continuous flow [55]. In

Study on the interactions between melamine-cored Schiff bases with cucurbit[n]urils of different sizes and its application in detecting silver ions

• Jun-Xian Gou,
• Yang Luo,
• Xi-Nan Yang,
• Wei Zhang,
• Ji-Hong Lu,
• Zhu Tao and
• Xin Xiao

Beilstein J. Org. Chem. 2021, 17, 2950–2958, doi:10.3762/bjoc.17.204

• mechanism of Q[7]-TBT towards Ag+, a UV–vis titration experiment was carried out. As shown in Figure 6, with the continuous addition of Ag+, the absorbance of Q[7]-TBT continues to increase at λmax = 258 nm, which is caused by the n–π* transition of Q[7]-TBT. Therefore, it can be further inferred that Ag

Host–guest interaction and properties of cucurbit[8]uril with chloramphenicol

• Lin Zhang,
• Jun Zheng,
• Guangyan Luo,
• Xiaoyue Li,
• Yunqian Zhang,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2021, 17, 2832–2839, doi:10.3762/bjoc.17.194

• ] and CPE was investigated using UV–vis spectroscopy utilizing the molar ratio and Job's method under neutral conditions (Figure 3). Figure 3A shows that CPE has a strong absorption peak at λ = 278 nm and the absorption intensity gradually decreases after the continuous addition of Q[8]. When n(Q[8])/n

Electrocatalytic C(sp³)–H/C(sp)–H cross-coupling in continuous flow through TEMPO/copper relay catalysis

• Bin Guo and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2021, 17, 2650–2656, doi:10.3762/bjoc.17.178

• terminal alkynes has been achieved in a continuous-flow microreactor through 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)/copper relay catalysis. The reaction is easily scalable and requires low concentration of supporting electrolyte and no external chemical oxidants or ligands, providing straightforward

• and sustainable access to 2-functionalized tetrahydroisoquinolines. Keywords: continuous flow; copper; catalysis; dehydrogenative cross-coupling; electrochemistry; Introduction The dehydrogenative cross-coupling of two C–H bonds represents an ideal strategy for the construction of C–C bonds [1][2

• reaction of tetrahydroisoquinolines with terminal alkynes (Scheme 1C) [10]. The chiral ligand was found to be critical for the stereoinduction as well as product formation for these electrochemical reactions that are conducted in batch. Continuous-flow electrochemical microreactors offer several advantages

Adjusting the length of supramolecular polymer bottlebrushes by top-down approaches

• Tobias Klein,
• Franka V. Gruschwitz,
• Maren T. Kuchenbrod,
• Ivo Nischang,
• Stephanie Hoeppener and
• Johannes C. Brendel

Beilstein J. Org. Chem. 2021, 17, 2621–2628, doi:10.3762/bjoc.17.175

• technology due to the rapid mixing of the sample [28]. In DAC, the sample holder performs an additional rotation besides the main rotor rotation, resulting in a continuous change of the direction of the centrifugal force [28]. This change induces a strong agitation of the solution and generates large shear

• ) decreased slightly and shifted to a lower elution time. For the BTU sample, even a new peak was formed at 10 to 20 min, corresponding to the formation of short structures. Continuous US for a cumulated time of 5 s resulted in the disappearance of the main peaks and the appearance of a broad distribution

• characterization. Acknowledgements The authors thank Prof. Ulrich S. Schubert for his continuous support and access to excellent research facilities. Funding T. K., F. V. G., and J. C. B. thank the German Science Foundation (DFG) for generous funding within the Emmy Noether Programme (Project-ID: 358263073

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• temperature with continuous stirring until the end of the reaction. After reaction completion, the mixture was poured into water, extracted with ethyl acetate, and the combined organic extracts were washed with saturated NaHCO3 solution and water. After drying and evaporation of the solvent in vacuo, crude

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• process in a continuous-flow reactor. The mechanistic studies indicated that a nickel hydride intermediate generated with C(sp3)–H as the hydride source is involved in this catalytic transformation. The hydronickelation step results in the sterically less hindered vinylnickel intermediate 15-I, which

• under slightly modified reaction conditions with exclusion of the nickel catalyst (Scheme 36) [113]. Acylation The ketone motif is an important functional group in pharmaceuticals, agrochemicals, and functional materials [114][115][116][117]. Hence continuous efforts devoted to developing a convenient

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• continuous development and improvement of polymerization techniques, more and more diverse copolymers can be synthesized. Very recently, Kertsomboon et al. succeeded in preparing a copolymer (poly(AAm-co-MDO)) of acrylamide and a degradable, hydrophobic monomer based on a ring opening polymerisation of

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• are crucial. In 2018, Ackermann and co-workers described a novel room temperature C–H arylation by using a continuous visible light photo-flow technique, allied with a manganese photocatalyst CpMn(CO)3 [142]. The new flow protocol enabled the synthesis of several arene- and heterocyclic-based

Cerium-photocatalyzed aerobic oxidation of benzylic alcohols to aldehydes and ketones

• Girish Suresh Yedase,
• Sumit Kumar,
• Jessica Stahl,
• Burkhard König and
• Veera Reddy Yatham

Beilstein J. Org. Chem. 2021, 17, 1727–1732, doi:10.3762/bjoc.17.121

• this cerium-photocatalyzed aerobic oxidation of alcohols prompted us to conduct some preliminary mechanistic studies (Figure 1). As anticipated, the ON/OFF irradiation experiments confirmed that our reaction required a continuous blue light irradiation (see Supporting Information File 1). The

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• substrate scope and functional group tolerance is highly desirable. As part of our continuous efforts to prepare biologically active DIM derivatives [38], we herein report an innovative approach to synthesize unsymmetrical 3,3'-diindolylmethanes (DIMs) with a fluoromethyl-containing quaternary carbon center