Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• Brønsted acid to generate (N-acyl)(propargyl)imine 90 as intermediate which added to the deprotonated phosphoric acid to form phosphate ester 91 as the next intermediate through an equilibrium process. Then, 1,2-addition by the C3 position of the heteroarene ring to the acylimine intermediate afforded the

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• the graph. In addition, we confirmed that isolated cyclopropane 1e did not change upon treatment with (diacetoxyiodo)benzene and tetrabutylammonium iodide. These findings indicate that no equilibrium existed between cyclopropane 1e and dihydrofuran 8e, and that these products were competitively formed

Light-responsive rotaxane-based materials: inducing motion in the solid state

• Adrian Saura-Sanmartin

Beilstein J. Org. Chem. 2023, 19, 873–880, doi:10.3762/bjoc.19.64

• examples, a light input leads to the observation of motion into condensed phases, both at the level of intertwined components and in terms of macroscopic changes. Despite these promising results reported so far, there are some issues which should be overcome, such as the photostationary equilibrium of some

A fluorescent probe for detection of Hg²⁺ ions constructed by tetramethyl cucurbit[6]uril and 1,2-bis(4-pyridyl)ethene

• Xiaoqian Chen,
• Naqin Yang,
• Yue Ma,
• Xinan Yang and
• Peihua Ma

Beilstein J. Org. Chem. 2023, 19, 864–872, doi:10.3762/bjoc.19.63

• that TMeQ[6] and G form an inclusion complex with a host–guest ratio of 1:1 and the equilibrium association constant (Ka) was 2.494 × 104 M−1. The G@TMeQ[6] fluorescent probe can sensitively recognize Hg2+ ions by fluorescence enhancement. The linear range is 0.33 × 10−5–1.65 × 10−5 mol·L−1, R2

• ] (1.0 × 10−4 mol·L−1, 1.00 mL) was gradually added to the aqueous solution of G, and the exothermic isotherms (Figure S1 in Supporting Information File 1) and thermodynamic data (Table 1) were obtained. The equilibrium association constant (Ka) of G and TMeQ[6] is 2.494 × 104 M−1, ΔH = −88.43 kJ/mol

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• observed in both MeCN and DMF which was in equilibrium with the starting compounds in a ratio of approximately 1:2. The addition of a base or any thiophile always caused only the decomposition to a complex mixture of products in which no ECR product was detected. Next, we performed modification of the

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• Michael acceptor. A number of thiols was taken as the model compounds. The reaction was performed under thermodynamic conditions reported in [41], to compare the thermodynamically controlled stereoselectivity of L7 and L1. The use of a 2 molar excess of K2CO3 induces the equilibrium between the isomers

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• studied compound. After mixing polynucleotides/protein with studied compounds it was observed that the equilibrium was reached in less than 120 seconds. Compounds Phen-Py-1 and Phen-Py-2 showed a decrease of their excimer fluorescence emission intensity upon time. Therefore, buffer solutions of compounds

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• then involved in the next catalytic cycle and thus removed from the equilibrium between Int4 and Pr + CuI. In addition, since TS2 is an early transition state and the potential is concomitantly very flat, only TS2_2 was found by means of regular optimization towards a first order saddle point. For the

Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• for preparation. On the other hand, similar methods such as spray-drying do not provide intimate contact between the three types of components for a sufficient period of time to reach the association–dissociation equilibrium [1][27][67]. In this study, the recovery yields were in the range of 51.5

Recommendations for performing measurements of apparent equilibrium constants of enzyme-catalyzed reactions and for reporting the results of these measurements

• Robert N. Goldberg,
• Robert T. Giessmann,
• Peter J. Halling,
• Carsten Kettner and
• Hans V. Westerhoff

Beilstein J. Org. Chem. 2023, 19, 303–316, doi:10.3762/bjoc.19.26

• , Free University Amsterdam, The Netherlands School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, UK 10.3762/bjoc.19.26 Abstract The measurement of values of apparent equilibrium constants K′ for enzyme-catalyzed reactions involve a substantial

• number of critical details, neglect of which could lead to systematic errors. Here, interferences, impurities in the substances used, and failure to achieve equilibrium are matters of substantial consequence. Careful reporting of results is of great importance if the results are to have archival value

• . Thus, attention must be paid to the identification of the substances, specification of the reaction(s), the conditions of reaction, the definition of the equilibrium constant(s) and standard states, the use of standard nomenclature, symbols, and units, and uncertainties. This document contains a

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• tetracoordinate phosphorus compounds that allows scaling of the readily accessible DFT chemical shifts. The present method follows established norms [15] of optimization of compound geometries in solution and weighting of the calculated chemical shifts on the basis of calculated equilibrium ratios in solutions of

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• . Interestingly, irradiation at 365 nm even in the presence of photosensitizer and O2 failed to furnish (+)-jungermatrobrunin A (89), and 90 was obtained as the sole product, albeit in low yield (14%). Attempts to optimize the yield always afforded recovered 88, hinting at a potential equilibrium between 88 and

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements

• Alexios I. Vicatos,
• Zakiena Hoossen and
• Mino R. Caira

Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184

• at 70 °C, but a very slight turbidity was still observed in the β-CD·BES solution. The solutions were left to stir for an additional 3 hours (to allow for the complex equilibrium to be achieved), after which they were filtered and prepared for slow cooling in a Dewar flask. Crystals appeared after 3

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• enone 10 to the corresponding allylic alcohol, followed by a Au-catalyzed alkyne hydration, providing hemiketal 11. This intermediate was in equilibrium with hydroxy-ketone 12, which was suitable for a SmI2-promoted cyclization, affording intermediate 13 selectively, already bearing rings C and D. The

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• , thus preventing the equilibrium between the gas and liquid phases and allowing to bypass the further step which would have involved removing these components by vacuum distillation. Although not shown in Figure 1, the addition of a second condenser and collection flask perpendicular, as in a

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• SPINOL [4][5] (Figure 1). The great success of these CPAs in asymmetric organocatalysis, is demonstrated by the publication of thousands of articles and reviews [6][7][8][9][10][11][12][13][14][15][16][17]. In all cases the C2-symmetry is required because of the prototropic tautomeric equilibrium in the

• exploratory work, thiophosphorus acids were chosen due to their appropriate acidity and intrinsic chirality. Thiophosphorus acids undergo a tautomeric equilibrium between the thiolic and the thionic forms [22] (Scheme 1). If the substituents R1 and R2 are different, the phosphorus atom is always chiral

• -, 2,4,6-Me3C6H2-, 2,4,6-iPr3C6H2-, Ph3Si-, etc. Project strategy and requirements for C1-symmetrical CPAs. BINOL CPA and C1-symmetrical CPA targets 1–4. The thiolic/thionic tautomeric equilibrium in thiophosphorus acids. Synthesis of tryptophol-derived thiophosphorus acid 1. Synthesis of indole-derived

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• equilibrium to the adamantane form by forming a stable boronate adduct 18 having a diamantane structure through the reaction with phenylboronic acid. Note that product 18 contains an unprecedented 2,4-dioxa-1,5,7,10-tetraaza-3-boraadamantane motif (Scheme 4). This result demonstrates that N-amino-substituted

Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies

• Attila Palágyi,
• Jindřich Jindřich,
• Juraj Dian and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2022, 18, 1346–1354, doi:10.3762/bjoc.18.140

• hydrophilic outer surface and hydrophobic cavity. This cavity can encapsulate another lipophilic guest molecule and thus form an inclusion complex [3][4]. This phenomenon is reversible and leads to an equilibrium between encapsulated and free guest. A staggering number of inclusion complexes of CDs with

• dissolution of the pro-fragrance, which influenced the equilibrium between dissociation and formation reactions. The integrals of the imine group signal at 8.30 ppm measured at various time intervals were depicted as a function of time for all the samples with pH from 3 to 12.8. Data were fitted by a

• monotonic (except for low pH values). A substantial difference is seen between acidic conditions, under which the imino-β-CD is unstable, and the benzaldehyde releases fast over the time course investigated, and basic conditions, under which the benzaldehyde is released slowly. In all cases, equilibrium

Computational model predicts protein binding sites of a luminescent ligand equipped with guanidiniocarbonyl-pyrrole groups

• Neda Rafieiolhosseini,
• Matthias Killa,
• Thorben Neumann,
• Niklas Tötsch,
• Jean-Noël Grad,
• Alexander Höing,
• Thies Dirksmeyer,
• Jochen Niemeyer,
• Christian Ottmann,
• Shirley K. Knauer,
• Michael Giese,
• Jens Voskuhl and
• Daniel Hoffmann

Beilstein J. Org. Chem. 2022, 18, 1322–1331, doi:10.3762/bjoc.18.137

• the total energy. where ki is the spring constant, li is the distance between bonded beads i and i+1, and lieq is the corresponding distance at equilibrium, Eg represents the affinity of protein toward GCP or lysine at a specific grid point. In this study, l1 and l4, i.e. the equilibrium lengths for

• the springs connecting GCP to lysine, have been selected to be 6 Å and l2 and l3, i.e. the equilibrium lengths for the springs connecting lysine to AIE, have been selected to be 13 Å. The value of the spring constants in bead-spring models with Gaussian probability distribution is inversely

• proportional to the square of the equilibrium length of the spring [36]. Based on that, the values of k1 and k4 (spring constants for GCP-Lys bonds) were chosen to be 12 kBT/Å2 while the values of k2 and k3 (spring constants for Lys-AIE bonds) were chosen to be 3 kBT/Å2. With these parameters, the sum of

Make or break: the thermodynamic equilibrium of polyphosphate kinase-catalysed reactions

• Michael Keppler,
• Sandra Moser,
• Henning J. Jessen,
• Christoph Held and
• Jennifer N. Andexer

Beilstein J. Org. Chem. 2022, 18, 1278–1288, doi:10.3762/bjoc.18.134

• phosphate transfer potentials that are characterised by reaction yields close to full conversion, the PPK-catalysed reaction reaches an equilibrium in which about 30% ADP is left. These results were obtained for PPK1 and PPK2 enzymes, and are supported by theoretical data on the basic reaction. At high

• substrate/product ratio is an important parameter for kinetics and for the reaction equilibrium, as it defines how much conversion will be achieved [25]. For acetate kinase a conversion of at least 90% using stoichiometric amounts of ADP and acetylphosphate was reported [26]. The reaction of pyruvate kinase

• (phosphoenolpyruvate as phosphate donor) is strongly favouring ATP synthesis both in vivo and in vitro, this reaction was originally considered to be irreversible in cells and a point of flux control. Newer findings showed the reaction to be actually an equilibrium, although positioned far on the product side [27][28

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• -ones 4a–c occurs via the acid-catalyzed condensation of the aromatic aldehyde 1a–c and aniline (2) to produce imine intermediate 5 which is then protonated to the iminium species 6. In addition, ethyl 2,4-dioxovalerate (3) containing an activated methylene group is in fast equilibrium with enol

• (Scheme 2). The reaction of aromatic aldehyde 1a and aniline (2) in acidic environment is reversible [44] and therefore, according to Le Chatelier’s principle [45], the increase in the concentration of 1a or 2 will shift the equilibrium to the side of the iminium species 6. As the concentration of 2 was

• increased to 0.75 M as compared to 0.5 M of aldehyde 1a, the equilibrium would favor the side of iminium salt 6. However, the excess amount of the nucleophilic reactant 2 reacted with intermediate 6 and as a consequence, the yield of the product 4a decreased to 67% (Table 1, Scheme 2). The 1H NMR spectra of

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