Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• generate some hypotheses regarding the enzymatic process. First, considering the similar free energy of IEs A and B and the small kinetic barrier separating them, these isomers may exist in equilibrium in the enzyme active site. The relative amount of IEs A and B may then be determined by their proximity

• being followed (Figure 3). Lastly, considering the huge thermodynamic preference for the HP pathway, it is unlikely that a thermodynamic equilibrium exists between this pathway and the IE pathway. Rather, an equilibrium may exist between GGDP and LGDP, but once cyclization commences, the reactions will

• exchanging π-bonds for σ-bonds. In spite of the current calculations being performed in the gas phase, we may still generate some propositions regarding the enzymatic process. First, considering the similar free energy of IEs A and B and the low barrier between them, IEs A and B may exist in equilibrium in

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• equilibrium mixture of two isomeric forms. The inhibitory activity of the synthesized hydroxamic acids on HDAC4 and HDAC8 isoforms shows that most of them are prone to inhibit HDAC8 isoform rather than HDAC4. The most potent inhibitor of both the HDAC4 and HDAC8 isoforms was found to be N-hydroxy-6-[6-methyl

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• the anthraquinone ↔ 9,10-dihydroxyanthracene (DHA) equilibrium is shifted towards DHA [34][35]. To prove this premise, anthraquinone alone was ball milled, however, unreacted material was recovered and the formation of 9,10-dihydroxyanthracene was not spectroscopically detected. An analogous hydroxy

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74

• intermediate 3, as shown for the reaction of isoxazole 1g (Scheme 2). Taking into account that compounds 2 can potentially exist in pyridone and pyridole tautomeric forms, we performed calculations at the DFT B3LYP-D3/6-311+G(d,p) level of theory with SMD solvent model to evaluate this tautomeric equilibrium

A trustworthy mechanochemical route to isocyanides

• Francesco Basoccu,
• Federico Cuccu,
• Federico Casti,
• Rita Mocci,
• Claudia Fattuoni and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 732–737, doi:10.3762/bjoc.18.73

• diverse electronic distribution between aliphatic and aromatic formamides. Concerning aromatic amides, the presence of electron-withdrawing (EWG) or electron-donating groups (EDG) further affect the tautomeric equilibrium, promoting or weakening the reactivity of the substrates. In this case, the yields

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

• increased by 5 °C. The authors suggested that the use of RF heating may allow water splitting near the equilibrium voltage at room temperature. Although it was expected that the magnetic field applied by inductive heating would disturb the flowing current, mainly positive effects were observed. 3 Micro- and

• ) [93]. Cyclohexanone (25) was mixed with conc. formic acid, and a mixture of H2O2 (30%)/HNO3 (65%) in a PTFE reactor at rt. This led to the formation of the cyclic triperoxide 91 in 48% (isolated) yield. Interestingly, the equilibrium favors the formation of the trimer 91 over the corresponding dimeric

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

• further options. In particular, the protocol of acid addition and removal (upon base addition) may be elegantly replaced by using a suitable fuel acid thus opening the field of supramolecular catalysis for out-of-equilibrium processing. Toggling between intra- and intermolecular complexation in

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

• the position of the reaction equilibrium. By this, equilibrium conversion, selectivity, and yield were increased from 57.9% to 63.9%, 81.9% to 84.7%, and 47.5% to 54.1%, respectively. This indicates a reduction in molar volume from N-acetyl-ᴅ-glucosamine (GlcNAc) and pyruvate (Pyr) to Neu5Ac. In

• expressions from Groher et al. are used [8]. So far, different approaches have been attempted to increase the overall position of an equilibrium by using additional enzymes [12], different temperatures or high concentrations of the substrates [13]. In accordance with the principle of Le Chatelier, pressure

• can also be used to influence the position of an equilibrium given that the molar volume changes during the reaction [14]. High-pressure processing is gaining increasing attraction for the enhancement of enzymes [15]. It has been shown that pressure can influence enzymatic reactions, either in

Synthesis of a new water-soluble hexacarboxylated tribenzotriquinacene derivative and its competitive host–guest interaction for drug delivery

• Man-Ping Li,
• Nan Yang and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2022, 18, 539–548, doi:10.3762/bjoc.18.56

• SM, indicating that most of the MV had been released and gradually reached equilibrium. In addition, the proton signals (green Hd and He) of SM were located upfield in comparison with the free SM (see Figure 3) and the TBTQ-CB6SM complex, which might be because SM was embedded in the cavity of the

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• polarity on the keto–enol equilibrium of the 1,3-diketones, which influences the results of the [3 + 2] cycloaddition reactions under mild basic conditions, via nuclear magnetic resonance (NMR) spectroscopy. The 1H NMR spectra of 1-phenyl-1,3-butanedione (2a) in CDCl3 and in methanol-d4 indicated that the

• thermodynamical product. The solvent polarity also affects the keto–enol equilibrium of the intermediate II-D. In polar solvents, the keto tautomer is predominant as an electrophilic group for the intramolecular cyclization, while in nonpolar solvents, the enol tautomer could not accept a nucleophilic attack for

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• leading to the promotion of the elimination reaction. β-Pinene isomerization β-Pinene is a bicyclic monoterpene bearing an exocyclic C=C double bond that can be recovered in large quantities from the production processes of cellulose from the wood of conifers. β-Pinene is in equilibrium with the more

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• /mol less stable while IN2b is 2.0 kcal/mol more stable (Figure 1). As such, it is likely these two intermediates are strongly in equilibrium with no thermodynamic driving force favoring one over the other; moreover, the activation energies of the forward and reverse reactions are proportional. The

Trichloroacetic acid fueled practical amine purifications

• Aleena Thomas,
• Baptiste Gasch,
• Enzo Olivieri and
• Adrien Quintard

Beilstein J. Org. Chem. 2022, 18, 225–231, doi:10.3762/bjoc.18.26

• . Inspired by recent work on out of equilibrium molecular machinery, using trichloroacetic acid (TCA), we disclose a purification technique considerably decreasing the number of operations and the waste generation required for such purifications. At first, TCA triggers the precipitation of the amines through

• success. Keywords: amines; decarboxylation; eco-compatible; out of equilibrium; purification; Introduction Isolation of pure amines from reaction mixtures or natural extracts is crucial in modern organic chemistry. However, the most widely applied methods for these purifications have remained unchanged

• operations and the associated generation of waste, discovery of alternative purification techniques is mandatory. Avoiding waste accumulation, dissipative acids have recently found interesting applications in the field of out of equilibrium molecular switches and motors [5]. They enable the temporary

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• acknowledged, in his participation as a co-author of a chapter in “Progress in Physical Organic Chemistry” [31], that this equilibrium needs to be incorporated into treatments based on the magnitudes of the heat capacities of activation (∆Cp#). The need to incorporate the return from an ion pair to a covalent

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• -butoxycarbonyl (Boc) moiety around a C–N single bond (Figure 4a). It is known that some N-Boc-substituted heterocyclic compounds, including oxazolidines, consist of NMR spectra showing two sets of signals due to the dynamic equilibrium between the two conformers formed by the rotation of the Boc moiety, and

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

• product mixture (Scheme 3B), mainly due to a tautomeric equilibrium (Scheme 3C) [41]. Hartke and Lohmann [70] studied the reaction of β-NQS with secondary aliphatic amines in detail and observed that the 4-amino-1,2-naphthoquinone 21 products are yellow. However, reactions with primary aliphatic amines

• and reported that they were unable to obtain 4-arylamino-1,2-naphthoquinones from β-NQSNa but that these derivatives can be readily prepared from 4-ethoxy-1,2-naphthoquinone. Similarly, Yano and co-workers [72] studied the tautomeric equilibrium of 4-arylamino-1,2-naphthoquinones in DMSO-d6, pyridine

• equilibrium between A and B using semiempirical calculations (AM1 and PM3) and DFT (B3LYP/6-31G(d)) in the gas phase and water, where it was observed that in the gas phase B is the most stable, while in water A is formed, which is in agreement with the experimental results reported in the literature. There

Effect of a twin-emitter design strategy on a previously reported thermally activated delayed fluorescence organic light-emitting diode

• Ettore Crovini,
• Zhen Zhang,
• Yu Kusakabe,
• Yongxia Ren,
• Yoshimasa Wada,
• Bilal A. Naqvi,
• Prakhar Sahay,
• Tomas Matulaitis,
• Stefan Diesing,
• Ifor D. W. Samuel,
• Wolfgang Brütting,
• Katsuaki Suzuki,
• Hironori Kaji,
• Stefan Bräse and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2021, 17, 2894–2905, doi:10.3762/bjoc.17.197

• . As stated above, this change of orientation in relation to the used processing conditions is not unexpected and confirms – once more – that an important driving force for non-isotropic emitter orientation upon vacuum deposition is the non-equilibrium situation at the surface of a growing film, as

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

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

• 1.3 h in artificial gastric juice (pH 1.2) and its release rate was 88.19%. CPE@Q[8] basically reached a release equilibrium after 9 h and the cumulative release rate was 51.26%. It is possible that the inclusion of CPE in Q[8] causes its release rate to be reduced and has a slow-release effect. In

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• rotation of the thioketone carbon–N-pyrrolidine bond, are energetically accessible, in agreement with the two set of signals observed by 1H NMR spectroscopy (energy differences between conformers lower than 1 kcal·mol–1 in both cases). However, this equilibrium is strongly affected by the coordination to

• nickel or palladium atoms. As far as the L1-Ni complex was concerned, this fluxional equilibrium disappeared due to metal coordination. In this case, complexes involving conformer B were highly energetic due to steric repulsion between the CO2Me substituents of the pyrrolidine ring. Thus, only one set of

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• not with acetic acid, it appears that protonation of the pyrrolidine-based enaminones with this weak acid must be readily reversible. Thus the critical isomerization equilibrium postulated to be essential for pyrrolizine formation (see Scheme 3) appears not to operate to any appreciable extent with

Synthesis and investigation on optical and electrochemical properties of 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridines

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 2450–2461, doi:10.3762/bjoc.17.162

• value, while the calculated LUMO energy was less negative. This can be explained by the fact that the calculations were achieved based on an equilibrium conformer. Conclusion In conclusion, we developed a convenient synthesis of novel 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridines starting from

• a PGSTAT30 Autolab potentiostat. Theoretical calculations The theoretical studies were realized in vacuum with the Gaussian 09 program [70]. The geometry of the equilibrium conformer at the ground state was first found at AM1 level. Then, further optimization through density functional theory (DFT

Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions

• Andrey I. Puzanov,
• Dmitry S. Ryabukhin,
• Anna S. Zalivatskaya,
• Dmitriy N. Zakusilo,
• Darya S. Mikson,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2417–2424, doi:10.3762/bjoc.17.158

• -protonated species Aa–d is extremely energetically favorable. For the second protonation (reaction A→B) leading to dications Ba–d, the ΔG298 values vary from −28.6 to 18.3 kJ/mol. Although the second protonations are sometimes mildly endergonic (and hence there would be an unfavourable equilibrium between

• ), oxadiazole 3a gave the product of hydration of the acetylene bond (4d, yield of 65%) existing in solution as equilibrium between ketone and enol forms in a ratio of 1.2:1 according to NMR data (see Supporting Information File 1). Then, reactions of 5-acetylenyl-1,2,4-oxadiazole 3a–d with arenes (benzene and

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• inhibit the formation of the reactive enolate by driving the enol/enolate equilibrium toward the enol form. While these considerations seemed discouraging, we were able to define a set of base-free/water-rich reaction conditions suitable for our catalytic system where the formation of the alkylated

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• participating directly as the nucleophile. First proposed anion-binding mechanism in the thiourea-catalyzed acetalization of benzaldehyde. a) Thiourea-catalyzed enantioselective acyl-Pictet–Spengler reaction of tryptamine-derived imines 4. b) Equilibrium between the ionic (SN1-type mechanism) and neutral form