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

• . However, if one is willing to settle for a classification of the mechanism as unimolecular or bimolecular accompanied by an approximate measure of the extents of bond-making and bond-breaking at the sulfur atom involved at the transition state, one can use a linear free energy relationship (LFER) approach

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• reaction free energy and barrier are −9.5 and 14.5 kcal mol−1 with methanol, respectively and −11.1 and 13.5 kcal mol−1 with dichloromethane, respectively (Figure 3). For the formation of the five-membered lactone 18 (path a), 17 → 18, the reaction proceeds via a barrierless path and the solvent corrected

• reaction free energies are −17.2 and −18.0 kcal mol−1 with methanol and dichloromethane, respectively. For the formation of the six-membered lactone 19 (path b), 17 → 19, the solvent corrected reaction free energy and barrier are −5.4 and 14.5 kcal mol−1 in methanol, respectively and −7.1 and 13.4 kcal mol

• epoxide 7, the relative free energy of 7b is higher by 10.3 kcal mol−1 than that of 7a (Figure 5). Conclusion In summary, we successfully synthesized hydroxylated cyclooctane β-amino acid 6 and its derivatives 8, 10, and 13 starting from β-lactam 2. The regioselective synthesis of lactone 8, which is a

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• indicated in the two-dimensional projection in the space of PC1 and PC2, where colouring is made by relative free energy as obtained from Boltzmann reweighting using 10th order Maclaurin series expansion [92][93]. In both isomers, the first three clusters represent about 53% of the total conformational

• frame and is coloured according to its corresponding re-weighted relative free energy. Data is calculated on the cumulative last 500 ns of 15 accelerated molecular dynamics runs for each SMC peptide. Molecular modelling of the conformational preferences of the SMC stapled peptides P5 (with cis or trans

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• , endergonic by 18.8 kcal·mol−1 (gas phase) and 20.1 kcal·mol−1 (1,4-dioxane with PCM); almost thrice the Gibbs free energy for the same reaction with DABCO as a HAT abstractor. The barrierless character is supported by NEB-TS calculations (vide infra) (Supporting Information File 1, Figure S16). Both these

• the Evans–Polanyi principle, that relates the rate coefficients of a reaction step to their free energy (for which the BDE difference is a proxy) [35][36][37]. When considered together with Hammond´s postulate [38], the Evans–Polanyi principle (E-PP) generates the often used rule-of-thumb that good

• catalysts and photocatalysts [9][10][11][12][21][22][23]. Previous reports of DABCO as hydrogen abstractor in HAT reactions and this work. Free energy profile for the HAT step reactions between isovaleraldehyde with (top) DABCO and (bottom) quinuclidine radical cations. The red lines are for the gas phase

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• the Michael adducts has the lowest Gibbs free energy of activation of 40.4 kJ·mol−1. The Gibbs free energies of activations for the (S,S)-C2 catalyst are only slightly higher than those for the (S,R)-C2 catalyst. These calculations support the experimental observation that the configuration of the

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• ; mechanisms of copper photocatalysis; photoinduced copper-based catalysis; photoredox catalysis; special features of copper photocatalysis; Introduction Solar light is an inexhaustible and free energy source for green plants and bacteria. Photosynthetic organisms absorb solar energy and convert it into

Nomimicins B–D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura

• Zhiwei Zhang,
• Tao Zhou,
• Taehui Yang,
• Keisuke Fukaya,
• Enjuro Harunari,
• Shun Saito,
• Katsuhisa Yamada,
• Chiaki Imada,
• Daisuke Urabe and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2194–2202, doi:10.3762/bjoc.17.141

• effects at 244 and 298 nm, matched well with the calculated one of 4 (Figure 4). Noteworthy is that 4a and 4b (Tables S4–S7, Supporting Information File 1) have a lower free energy than 4c and 4d, and the calculated spectra for 4a and 4b are similar to the experimental one, indicating that 4a and 4b are

• calculations were carried out at the same level of theory to confirm the absence of imaginary frequencies and obtain thermal corrections for the Gibbs free energy. After eliminating duplicated structures with the threshold of 0.01 Å RMSD, the single-point energy was calculated at the M06-2X/def2-TZVP-SMD level

• of theory, affording 24 conformers within 3.0 kcal/mol from the minimum Gibbs free energy. The ECD spectrum of each conformer was simulated by the TDDFT calculation of 25 excited states at the ωB97X-D/def2-TZVP-PCM level of theory. The spectrum of structure 4a was created by the weighted average of

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

• mixtures are characterized by interactions A–A, A–B as well as B–B, which are all different from each other. The mixing process is thus accompanied by an enthalpy change and possibly by an additional entropy contribution. The free energy of mixing can thus become positive (spontaneous segregation) if the

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• calculated to be as low as −6.10 eV, it is obvious that also this approach fails in sufficiently describing the activity of phosphines in catalyzing oxa-Michael reactions. To resolve this issue, the Gibbs free energy (ΔG) of the reaction of TPP, MMTPP, TMTPP, and PMe3 with acrylonitrile leading to zwitterion

• formation (Figure 3, right) was calculated in chloroform. The Michael acceptor affinity (MAA) of the nucleophiles is then given by the Gibbs free energy of the back reaction [37]. The respective energy differences calculated at the B3LYP/def2-TZVPPD level of theory are −96.3 kJ/mol (TPP), −94.2 kJ/mol

• effects of chloroform have been considered for calculation of the Gibbs free energy (ΔG) of zwitterion formation and were calculated by the conductor-like screening model (COSMO) [53][54] with a dielectric constant of 4.8 and a radius of 3.17. Our best estimate for the calculation of zwitterion energies

Co-crystallization of an organic solid and a tetraaryladamantane at room temperature

• Fabian Rami,
• Jan Nowak,
• Felix Krupp,
• Wolfgang Frey and
• Clemens Richert

Beilstein J. Org. Chem. 2021, 17, 1476–1480, doi:10.3762/bjoc.17.103

• lower minimum in free energy, with both solvent and the competing organic molecule being eliminated during crystallization [20]. Thermal crystallization, induced by cooling a saturated solution of a TAA in the liquid guest molecule, is what has been used thus far by us to produce EnOCs. We suspected

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• set). Enthalpy and Gibbs free energy values referenced against the starting value for the substrates and catalyst are given in kcal/mol. Scope of glycosyl acceptors for glycosylation with pivaloyl-protected mannosyl fluoride α-1a in liquid SO2. aUnless otherwise stated, reactions were carried out by

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• heterogeneity can markedly complicate folding. In addition, the stability of the amide bonds translates into the thermodynamic stability of the protein structures by altering the free energy of folding. Fluoroprolines alter the relative thermodynamic stability of the amide conformers. Compared to proline, R-Flp

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

•  5) [38]. Tidwell et al. explored the influence of a CF3 group on the solvolysis reaction of various benzylic sulfonate derivatives [39][40]. They found a linear free-energy relationship between the solvolysis rate of sulfonate 13f in different solvents compared to the one of 2-adamantyl tosylate

• group. Remarkably, they found that CF3 deactivates to such an extent that benzylic tosylate 13f was approximately 10 times less reactive than benzylic tosylate 17 (Figure 2, top). Similarly to the previous study, the Grunwald–Winstein plot [44] gave a linear free-energy relationship between the

• preliminary results, Tidwell et al. envisioned the possibility to study the solvolysis reaction of secondary benzylic sulfonates [48]. In tertiary benzylic sulfonates [39][43], a linear free-energy relationship between the solvolysis rate for the secondary benzylic tosylates 21 (Figure 4) and YOTs was

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• interactions and secondary interactions such as π–π stacking [34][35][36][37][38][39][40]. The size and shape could be tuned through the free energy and the enthalpy/entropy interplay in the assembly process, which again are encoded in the molecular building block structure [31][37]. Supramolecular structures

• binding constants Kx, which are related to the free energy change ΔG and thus due to ΔG = ΔH − TΔS, also the entropy change ΔS is revealed. Table 5 summarizes the results from the full titration curve fitting. The values correlate to the binding of one monomer of the polymer to Flavy and/or photoacid. For

• that an association occurs because of hydrophobic effects, likely due to the slight hydrophobic nature of Flavy. The total free energy ΔGtotal is negative, which shows that the overall assembly process is spontaneous. The molar ratio (x-axis in Figure 8) representing the increasing addition of poly

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• thermodynamic properties, including the binding constant Kb, the reaction stoichiometry (n), the observed molar calorimetric enthalpy ΔHobs, the entropy ΔS, the heat capacity of the binding ΔCp,obs, and the change in the Gibbs free energy ΔG. As a result, ITC is used to provide a complete thermodynamic

• by the net charge but by different localised charges on the accessible surface residues in the protein monomers. This creates a delicate balance between the interface interaction and the desolvation energy, which affects the binding free energy. After binding occurs, ionisation changes can be induced

• in the protein molecules due to proton uptake and release. Therefore, these events are strongly affected by the pH value and the ionic strength. Variation of the pH value or the ionic strength can result in substantial binding free energy changes [48] or changes in the binding preference [49

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• (Figure 2). The substituents COOH, SH, COO− and O− give rise to almost complete coordination of the cis isomer. In contrast to bimolecular coordination [12] the intramolecular coordination in the substituted cis isomers, obviously, does not follow a clear linear free energy relationship. Steric hindrance

Conformational preferences of fluorine-containing agrochemicals and their implications for lipophilicity prediction

• Daniela Rodrigues Silva,
• Joyce K. Daré and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2020, 16, 2469–2476, doi:10.3762/bjoc.16.200

• ., becomes less stabilizing, in the order Iag < Iga < Igg. The difference in energy between Iag and Iga is somehow small (0.5 kcal mol−1), and these conformers are equally stable according to the relative Gibbs free energy ΔG (Boltzmann populations of 50% and 49%, respectively). The inclusion of an implicit

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

• Poulami Jana,
• Filip Šupljika,
• Carsten Schmuck and
• Ivo Piantanida

Beilstein J. Org. Chem. 2020, 16, 2201–2211, doi:10.3762/bjoc.16.185

• calorimetry experiments (ITC), which allowed us to determine all thermodynamic components simultaneously in a single experiment (the equilibrium binding constant (Ka), reaction Gibbs free energy of binding (ΔrG), reaction enthalpy (ΔrH), reaction entropy (ΔrS), and the stoichiometry (n) of the complex formed

• reaction entropy change, indicating favourable enthalpic (exothermic) and entropic contribution to the reaction Gibbs free energy change. This means that the reaction is both enthalpically and entropically driven. However, secondary binding site (n > 0.4; excess of 4 over DNA primarily binding site) is

• free energy change. Moreover, at these conditions (n > 0.6) also strong new ICD bands are visible, pointing out that binding of surplus molecules of 4 is not random but well organised along the chiral double helix. Furthermore, such highly positively charged systems, which efficiently wrap around DNA

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

• Esra Demir,
• Ozlem Sari,
• Yasin Çetinkaya,
• Ufuk Atmaca,
• Safiye Sağ Erdem and
• Murat Çelik

Beilstein J. Org. Chem. 2020, 16, 1805–1819, doi:10.3762/bjoc.16.148

• elimination of hydrated HCl and formation of 13. The calculated free energy of activation was found to be 15.4 kcal/mol with respect to RC1 (7f+CSI) (Figure 5). The final step of path 2 takes place from RC5 (13+H2O) passing through TS5 and forming the target product 9f. This step requires an activation free

• energy of 16.2 kcal/mol with respect to the initial reactant complex RC1 (7f+CSI) (Figure 5). The overall process is exothermic by 56.2 kcal/mol. Three-dimensional (3D) views of all the optimized structures of path 2 are illustrated in Supporting Information File 1, Figure S2. As can be seen from the

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• both cases. When inspecting the Gibbs-free energy diagram of the transformation of aldehydes 1a–c (Figure 2, Table 2 and Table 3), it is noteworthy that the main trends until the formation of isoindole intermediates 4a–c are very similar. However, there is a significant difference in the 4→12

• the transformation of trimethoxy derivative 1d reveals that dehydration is almost isoergonic (ΔG9d→11d = −1.6 kJ·mol−1), but the formation of the isoindole intermediate (11d→4d) is endergonic (unlike in the case of the three other derivatives), with a larger activation free energy (ΔG#11TS = 40.2

• conformer was identified for 23a and two for 23b (Figure 4). In the two preferred conformers of 23b (23b1 and 23b2), the plane of the ortho-formyl-substituted phenyl rings is twisted with 180° compared to each other. The Gibbs free energy difference between the two conformers is 4.1 kJ·mol−1 suggesting the

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• ratio results in an extremely efficient heat exchange. This maintains a narrow free energy profile in flow reactors and can enhance selectivity [43][53][54]. This also prevents potential hot spots forming due to a photothermal effect, which could potentially alter selectivity and lead to the loss of

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

• Panagiotis S. Gritzapis,
• Panayiotis C. Varras,
• Nikolaos-Panagiotis Andreou,
• Katerina R. Katsani,
• Konstantinos Dafnopoulos,
• George Psomas,
• Zisis V. Peitsinis,
• Alexandros E. Koumbis and
• Konstantina C. Fylaktakidou

Beilstein J. Org. Chem. 2020, 16, 337–350, doi:10.3762/bjoc.16.33

• chemical reaction below (Scheme 3). The activation free energy for the decarboxylation reaction is only 1.09 kcal/mol and by using Equation 4 (see theoretical calculations section) we find a rate constant kr = 9.87∙1011 s−1, characterizing the reaction as an ultrafast one, with a corresponding life-time of

• energy and free energy of activation are given in Equation 1 and Equation 2, respectively: For the calculation of the rate constant, kr, the Eyring’s classical Equation 3 was used, where in the above equation kB is the Boltzmann’s constant (1.380662∙10−23 J/K), h is the Planck’s constant (6.626176∙10−34

The reaction of arylmethyl isocyanides and arylmethylamines with xanthate esters: a facile and unexpected synthesis of carbamothioates

• Narasimhamurthy Rajeev,
• Toreshettahally R. Swaroop,
• Ahmad I. Alrawashdeh,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Seegehalli M. Anil,
• Kuppalli R. Kiran,
• Chandra,
• Paris E. Georghiou,
• Kanchugarakoppal S. Rangappa and
• Maralinganadoddi P. Sadashiva

Beilstein J. Org. Chem. 2020, 16, 159–167, doi:10.3762/bjoc.16.18

• -311++G(d,p) level of theory, with solvent corrections for chloroform, for two rotamers, namely 4cA and 4cB (generically represented as 4A and 4B in Figure 3). These structures were generated based on the X-ray structure of 4c and afforded a computed Gibbs free energy difference of −1.769 kJ mol−1 in

A combinatorial approach to improving the performance of azoarene photoswitches

• Joaquin Calbo,
• Aditya R. Thawani,
• Rosina S. L. Gibson,
• Andrew J. P. White and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2019, 15, 2753–2764, doi:10.3762/bjoc.15.266

• inversely proportional to the rate constant, and this is exponentially dependent on the free-energy barrier according to Eyring theory. Thus, a small variation in the energy barrier of <1 kcal/mol leads to a change of few orders of magnitude in half-life. Vertical electronic transition energies for the

• arylazopyrazoles 4pzH-F2 (left) and 4pzMe-F2 (right). Free energy barriers calculated with respect to the corresponding ground-state Z-isomer are shown in red. Atom color coding: C in cyan, H in white, N in blue and F in pink. Noncovalent index (NCI) surfaces calculated for representative pyrrolidine-based ortho

Acid-catalyzed rearrangements in arenes: interconversions in the quaterphenyl series

• Sarah L. Skraba-Joiner,
• Carter J. Holt and
• Richard P. Johnson

Beilstein J. Org. Chem. 2019, 15, 2655–2663, doi:10.3762/bjoc.15.258

• frequency analysis but the large number of reaction paths precluded calculation of intrinsic reaction coordinates. Reported relative energies are from free energy calculations at 298 K. Pathways for terminal 1,2-phenyl shifts in quaterphenyl isomers calculated with IEFPCM(DCE)/B3LYP/6-31+G(d,p) theory