Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• -halides motivated us to use density functional theory (DFT) calculations to understand the preference of talose analogues to adopt 4C1-like conformations. DFT computations were performed using Gaussian 16 revision B.01 [67] with the CAM-B3LYP [68][69][70] functional and the Def2TZVP basis set [71], which

• allopyranoses; b) synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose integrating the 2,3-cis, 3,4-cis relationship for the halogens (this work). Direct comparison of 19F resonances of halogenated talose analogues 12–15 (19F NMR; 470 MHz, CDCl3). X-ray analysis of compound 13–15

• , 17, and α-ᴅ-talose 18. ORTEP diagram showing 50% thermal ellipsoid probability (except for 18): carbon (gray), oxygen (red), fluorine (green), chlorine (orange), bromine (dark red), iodine (purple), and hydrogen (white). Packing arrangement of compound compound 15; a) View down the b axis; b

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

• with stirring. Solution A (IO): IO (0.1 mol, 24.64 g) was dissolved in H2SO4 (100 mL) under stirring conditions in an ice bath, solution volume VA = 118 mL. Solution B (H2SO4 + HNO3): HNO3 (0.44 mol, 18.49 mL) was dissolved in H2SO4 (100 mL) under stirring conditions in an ice bath, solution volume VB

• = 112 mL. Continuous flow microreactor system The continuous flow microreactor system is shown in Figure 1. Solutions A and B were stored in two glass vials (500 mL) with lids and were preheated by two high-pressure PTFE pumps (pump A, pump B, JJRZ-10004F, Hangzhou JingJin Technology Co., Ltd.) and

• microreactor system. Two mixing setups: (a) a T-mixer and (b) a T-mixer combined with a homemade static mixer, and the effect of the two mixing setups on the mixing process; (c) the T-mixer and (d) the T-mixer plus the homemade static mixer effect of flow rate on conversion. Reaction conditions: H2SO4 mass

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• (Scheme 1). The triflate salt 7OTf was transformed into the corresponding bromide salt by XB-activated solvolysis of α-methylbenzyl bromide in wet acetonitrile [13]. The DAI salt 7Br crystallized from this solution in the monoclinic space group P21/n with a cell volume of 1447.91(3) Å3 (a = 5.4707(1) Å, b

• ), 0.1 M, 135 h at rt, 43%, (b) 1.5 equiv mCPBA, 3.0 equiv TfOH (at 0 °C), (DCM), 0.1 M, 20 h at rt, 85%, (c) 1.0 equiv NaBArF24, (acetone), 0.5 M, 2 h at 50 °C under microwave irradiation, 72%. Gold(I)-catalyzed cyclization of propargylic amide 11 as benchmark reaction for Au–Cl activation. Determined

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

• [13], plausible reaction pathways are proposed as seen in Scheme 6. At the cathode, one-electron reduction of the hydroxy group in diarylmethanol 1 generates H2 and the corresponding alkoxide ion A, which captures carbon dioxide to form carbonate ion B. Although it is currently unclear whether this

• proceeds in a stepwise or concerted manner, two-electron reduction of carbonate ion B generates the corresponding diphenylmethyl anion C, which reacts with carbon dioxide to produce a carbon–carbon bond that results in the formation of diphenyl acetate ion D. Electrochemical reduction of carbon dioxide

• B in DMSO solvent. Electrochemical reduction of intermediate B should occur in solution, and this would mean that intermediate B must be dissolved in the solvent used. DMSO is well known as a good solvent for dissolving organic metal salts. In this electrochemical reaction medium, a main counter

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

• , compounds 6–9 are products of alkylation of the nitrogen atom of the heterocycle. Thiones 6–9 were obtained in 40–79% yield (Scheme 1,b). The structures of synthesized compounds were confirmed by the spectral methods IR-, 1H NMR, 13C{1H} NMR spectroscopy (Figures S1–S18 in Supporting Information File 1

• groups (O1–H1···O2: the H1···O2 distance is 1.98(1) Å, the O1···O2 distance is 2.581(3) Å, angle O1–H1–O2 is 117°) and between hydroxy group O2–H2 and nitrogen atom N1 of the pyridine cycle (O2–H2···N1A/B: the H2···N1 distance is 1.75(1)/2.08(1) Å, the O2···N1 distance is 2.560(3)/2.893(3) Å, angle O2–H2

• 121.6°). In addition, the intermolecular H-bonding is observed between group O2–H2 of molecule A and the thione group C=S of molecule B (the distance H2A···S1B is 2.42(1) Å, the angle O2A–H2A–S1B is 161°). At the same time, for molecule B, there is a hydrogen bond between the O2B–H2B group with the

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

• several anticipated diagnostic ions, including the b-type ions from fragmented peptide bonds of the linker (Figure 9A). The study builds on the reactivity of free cysteine thiols, which are reacted on the proteome-wide level with iodoacetamide-alkyne via SN reaction. Similar as for the above-described DTB

• disadvantage of the TEV-linker might be the multistep synthesis. The labile and open search of the publicly available data revealed a set of diagnostic ions, both derived from the linker and the probe (Figure 10A and B). The structural motives of the diagnostic ions corroborate the above-described findings

• . The fragmentation of the triazole ring leaving the primary amine and b-ion resulting from the fragmentation of the TEV-recognition peptide sequence. The chemical cleavage of the linker to release probe–peptide conjugates is achieved mainly by the change of the pH or via reducing conditions to release

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

• product with 93% ee after 24 h, while the bifunctional primary amine-thiourea catalysts (system B) required 4 days to provide an adduct with similar enantioselectivity. Prolonged reaction time is in general the innate nature of organocatalytic reactions employing iminium activation approaches. With 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

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

• fluorinated alcohol solvents in NGT catalysis. a) Lewis acid activation of hypervalent iodine reagents can enhance the reactivity of these reagents. b) Charge-tagged iminoiodinanes display enhanced reactivity in aziridination reactions with unactivated olefins (ref. [34]). c) Here, we demonstrate that H

• atmosphere. a) 20 °C for 16 h, b) 50 °C for 16 h, c) 50 °C for 48 h, d) NMR yield, e) 1.2 equiv PhINTs was used, and f) 4.0 equiv of PhINTs at 20 °C for 48 h. Scope of nitrogen group transfer in the aziridination of aliphatic olefins. Conditions using synthesized iminoiodinane: 0.20 mmol cyclopentene (1b

• ), 0.40 mmol iminoiodinane 2, 1.0 mL HFIP, N2 atmosphere. Conditions using in situ-generated iminoiodinane: 0.20 mmol cyclopentene (1b), 0.20 mmol sulfonamide, 0.40 mmol iodosylbenzene (PhIO), 1.0 mL HFIP, N2 atmosphere. a) 20 °C for 16 h, b) 40 °C for 16 h. a) The broadening of the hydroxide proton

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

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

• Scheme 2 but is open to debate. Thus, formamide adds to the [D1]-aldehyde A to form hemiaminal B which eliminates D2O to give imine D. Deprotonation of formamide D forms the resonance and zwitterrion-stabilized isocyanate E [22]. We then hypothesize that zwitterion E rearranges with loss of CO2 to form

• preparation of 4d, a deuterated isocyanide was solely employed and for 4a,b and 4e,f, water was used as solvent. For the latter, product precipitates from the aqueous solution which deters undesirable side-reactions whilst also aiding rate of the reaction. The fifth MCR employed herein is the ubiquitous

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

• −’’ equivalents might serve as good reagents for the gem-difluorination of alkynes. Thus, we have examined the electrochemical oxidation of a solution of Bu4NBF4/CH2Cl2 containing 1a (0.5 mmol) in a divided cell using 8 mA or 16 mA (Scheme 1, method B, in-cell method). In-cell method means that EGA was generated

• analysis in the case of 16 mA [53]. With the successful formation of (5,5-difluorohexyl)benzene (2a) by the chemical (method A) and electrochemical oxidation (method B) methods in hand, we have investigated the scope and limitations of gem-difluorination for various alkynes (Table 2). Electrochemical

• oxidation of method B was conducted by using 8 mA. The reaction of but-3-yn-1-ylbenzene (1b) in method A gave the corresponding compound 2b in 21% isolated yield (Table 2, entry 1). The 19F NMR result indicated 63% yield. Because of the low molecular weight of 2b, the isolated yield might be somewhat lower

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

• insights for the molecular design of readily handled aromatic hydrocarbon radicals that possess both stability and reactivity. (a) Typical example of stable aromatic hydrocarbon radicals with 9-anthryl units. (b) Tail-to-tail σ-dimer formation by rotating anthryl group and spin center shift. (a) The

• structure of DAntM radical (left) and its spin delocalization on two anthryl units. (b) Plausible head-to-head σ-dimerization of the DAntM radical. (a) ESR spectrum of the DAntM radical (black line, Exp.) and its simulated pattern (red line, Sim.). (b) Hyperfine coupling constant of the DAntM radical. (a

• ) ESR spectrum of anthroxyl radical 5 (black line, Exp.) and its simulated pattern (red line, Sim.). (b) Hyperfine coupling constant of 5. (c) X-ray structure of 5. Hydrogen atoms are omitted for clarity. Cyclic voltammogram (CV) of DAntM cation. (a) CV measured with scan rate at 3.0 V s−1. (b) Scan

Cell-free protein synthesis with technical additives – expanding the parameter space of in vitro gene expression

• Tabea Bartsch,
• Stephan Lütz and
• Katrin Rosenthal

Beilstein J. Org. Chem. 2024, 20, 2242–2253, doi:10.3762/bjoc.20.192

• polyethylene glycol with a molecular weight of 8000 g/mol (PEG-8000), methylcellulose (MC), carboxymethylcellulose (CMC), choline chloride/urea (ChCl/urea), choline chloride/glycerol (ChCl/glycerol), and betaine/ethylene glycol (betaine/EG); the reference experiment is labeled as shaded bars. B) represents

• ), methylcellulose (MC), carboxymethylcellulose (CMC), choline chloride/urea (ChCl/urea), choline chloride/glycerol (ChCl/glycerol), and betaine/ethylene glycol (betaine/EG). The reference experiment is labeled as shaded bars. B) represents dimethyl sulfoxide (DMSO), methanol (MeOH), methyl tert-butyl ether (MTBE

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

• . (a) Strain-promoted azide–alkyne cycloaddition between DBA 5 and benzyl azide and (b) 1H NMR spectral change at 30 °C in CDCl3. Arrhenius plots of the rate constants for the reaction between 5 and benzyl azide in CDCl3. Proposed reaction mechanism for the formation of compound 6a. Free energy

• profiles (ΔG298 in kJ mol−1) calculated at the ωB97X-D/6-31G(d,p)/PCM (in CH2Cl2). Absorption (blue) and fluorescence (red) spectra of 6a (2 × 10−5 M) in CH2Cl2. (a) Crosslinking reaction of PVC-N3 (x = 0.11) with compound 5. (b,c) Strain-stress curves of PVC-N3 before (blue) and after (red) crosslinking

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

• , 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

• synthesis of β-keto amides 3 under conditions B was investigated (Scheme 3). 3-Oxo-N-phenyl-3-arylpropanamides 3a–l and 3-oxo-N-aryl-3-phenylpropanamides 3m–v could be produced in excellent yield from the hydrolysis of α-oxo ketene N,S-acetals under conditions B. The results showed that electron-donating as

• ) could also be obtained in 80% yield when the hydrolysis reaction of (E)-3-(benzylamino)-3-(ethylthio)-1-phenylprop-2-en-1-one (1aa) was carried out under conditions B. Furthermore, to explore the synthetic practicality of the two chemical processes, the synthesis of 2a and 3a on a gram scale was tested

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

• reaction in the presence of molecular sieves and 1.5-fold excess of aniline (conditions B) dramatically reduced the reaction time to 1 d, allowing isolation of diarylamine 3ac in 75% yield (Scheme 2). Next, we started to screen various heterocyclic 1,3-diketones with the model amine series. The reaction of

• calculated Hammett constants of heterocyclic substituents. Previously studied EWGs [53] are shown in the dashed block. The numbers in parentheses are σm and σp calculated [57] constants. Scope of functionalized amines in three-component condensation. Conditions A: 1a,b,h,i (0.2–0.5 mmol), 2e,i–k (0.2–0.75

• mmol) and acetone (1–2 mL) or acetone/CHCl3 (3 mL, 2:1), 60 °C. Conditions B: 1a (0.3–0.5 mmol), 2d,f–h (0.45–0.75 mmol), AcOH (30 mol %), molecular sieves 3 Å (300 mg) and acetone (1–2 mL), 60 °C. Strategies to access meta-substituted anilines. Synthesis of meta-substituted anilines from 1,2,4

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• alternariol (e.g., A, Figure 2), will not be included. Resorcylic lactones [22][23][24] structurally not related to alternariol-derived dibenzo-α-pyrones, like zearalenone (B), are similarly not part of this review. These types of resorcylic lactones could be easily differentiated by taking the involved

• respect seems to be available for alternariol or even for its derivatives. Compounds not containing a fully intact resorcylic acid (e.g., dendrocoumarin (C) [29], urolithin A (D) [30], or polygonumoside B (E) [31]) or containing more than the two hydroxy groups of the resorcylic acid (e.g., unnamed

• : 87.2 μg/mL) [115]. It furthermore had a negative effect on progesterone synthesis in porcine granulosa cells [100] and selectively inhibited human monoamine oxidase-A (MAO-A) with an IC50 value of 1.71 μM (but did not inhibit MAO-B) and was thus considered for the treatment of depression, Parkinson’s

Finding the most potent compounds using active learning on molecular pairs

• Zachary Fralish and
• Daniel Reker

Beilstein J. Org. Chem. 2024, 20, 2152–2162, doi:10.3762/bjoc.20.185

• pairing to identify the most potent inhibitors in adaptive learning campaigns. When comparing the performance of the tree-based and the deep neural network-based ActiveDelta approaches, we observed that AD-CP and AD-XGB showed no statistically significant difference at 100 iterations (p = 0.2, Figure 2A,B

• development. Comparison of active learning approaches. (A) Classic exploitative active learning uses individual molecular representations to predict absolute property values to select the most promising molecule from the learning set to add into the training set. (B) ActiveDelta learning uses paired molecular

• –C) The percentage of the top ten percentile most potent molecules (‘hits’) in the learning set identified over 100 iterations of active learning by (A) AD-CP and Chemprop (CP), (B) AD-XGB and XGBoost (XGB), and (C) Random Forest (RF) and random selection (Random). (D) Bar charts of the average

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

• 18). Reaction scope We then used optimized reaction conditions from Table 1, entry 16 (method A) and 12 (method B) to further explore the scope of the reaction (Scheme 2). By employing various EWG/EDG-substituted benzaldehydes and urea/thiourea/selenourea we synthesized novel Biginelli products 2a–q

• reaction (A) and examples of DHMP (B) and thiopyran-1,1-dioxide (C) containing drugs. Scope of the obtained Biginelli products 2a–q. Synthesis of SO2-containing enastron analogue 2r. Postmodification of the Biginelli product 2a. Optimization of reaction. Supporting Information Supporting Information File

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

• • can be generated by photoirradiation. On the other hand, the photoinduced homolysis of groups 13 and 14 interelement compounds with B–B, Si–Si, Sn–Sn bonds, etc. is generally impossible, because such E–E compounds have no isolated electronic pair. Therefore, the use of a photocatalyst (method 3) or

• hindrance. However, several examples of isocyanide insertion reactions into B–H and B–B bonds are known. For example, isocyanides coordinate to diborane (B2H6) or trialkylboranes (BR'3) to form Lewis acid–base complexes (RNC→BH3 or RNC→BR'3), but these complexes are thermally labile, and hydrogen or alkyl

• groups on boron are 1,2-shifted to the isocyanide carbon, yielding the compounds (H2B-C(=NR)-H or R'2B-C(=NR)-R') with the isocyanide inserted between the B–H or B–alkyl bond [45][46]. The insertion products easily underwent dimerization to afford 2,5-diboradihydropyrazine derivatives 16 (Scheme 10a

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

• using a series of nitriles with the sulfoxide 1a (Scheme 3). We noticed that the length of the alkyl chain has no impact on the yield (3a,b). However, the use of benzyl cyanide is completely deleterious for the reaction as no product was observed (3c). The presence of a chlorine atom at the alpha

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

• of different and particular structures [7][8]. Additionally, glycans can adopt a wide variety of different shapes; five-membered ring sugars can exhibit envelope and twist conformations usually represented on a pseudo-rotational wheel; while six-membered ring structures can adopt chair (C), boat (B

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

• application. Single droplets of the Pickering emulsion attached to a glass surface. Cage-like microstructure obtained via sequential Ugi reactions. AFM images of A) single domains and B) cross-linked CMC/chitosan polymer particles. Variations of microstructures obtained via sequential Ugi reactions. A) Cap

• -like structures at 5 mol % cross-linking agent relative to chitosan at the second stage. B) Denser packing of particles at 20 mol % cross-linking density at the first stage. Synthesis of cross-linked microgel labelled with aminofluorescein. Supporting Information Supporting Information File 46

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

• ][5][6]. For instance, pyrazoles serve as monoamine oxidase A and B inhibitors [7] and as COX-II inhibitors [8], making them valuable analgesics [9]. Furthermore, several blockbuster drugs, such as VIAGRA® [10], Celecoxib® [11], and Rimonabant [12], contain pyrazole cores. In addition, extensive

• method holds promise for the development of biologically active substances. In addition to acetoacetylcoumarins, the synthesis was also successfully conducted using acetylacetone [66]. Likewise, complex functionalized pyrazoles, such as triazolo[3,4-b]-1,3,4-thiadiazin-3-yl substituted 5-aminopyrazoles

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

• oxidation potential than the hydrazone, then the transformation initiates with the anodic generation of radical species Y•, that adds to the hydrazone leading ultimately to hydrazinyl radical F as well (route b). In both cases, a second SET anodic oxidation and deprotonation yields the functionalized

• . Initial SET oxidation of the partner As mentioned above, if the partner is more readily oxidized than the hydrazone, then the general mechanism of the process is as described in Scheme 20, following route (b) for the first anodic oxidation. While investigating the electrochemical oxidative C(sp2)–H