Substituent effects in N-acetylated phenylazopyrazole photoswitches

• Radek Tovtik,
• Dennis Marzin,
• Pia Weigel,
• Stefano Crespi and
• Nadja A. Simeth

Beilstein J. Org. Chem. 2025, 21, 830–838, doi:10.3762/bjoc.21.66

• a thermal half-life of 4.38 days, extends the thermal half-life significantly compared to the 19.7 minutes observed for NH-PAP-OMe. We subsequently analyzed the electronic effects on the thermal relaxation rates in our NAc-PAPs using Hammett parameters for the substituents in the para-position and

• found a trending behavior (cf. Figure 3). Specifically, the Hammett plot shows linear trends for both EWGs and EDGs, with a minimum for electron-neutral R = H and R = OH as an outlier, likely due to a contribution of tautomerization [50]. Both linear fits show high slope values, indicating a great

• thermodynamic properties, we decided to perform an Eyring analysis of two representative PAPs. We chose NAc-PAP-CN and NAc-PAP-OMe, which lie on two different ends of the Hammett plot and hence should reveal the difference in relaxation mechanism. We measured the temperature-dependency of their relaxation rates

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• experimentally achievable ee values. Maximal theoretical ee values are 70% "S" for Z-hydrazone and 70% "R" for E-hydrazone. The relatively high racemization barriers in 9 preclude a Curtin–Hammett scenario (with fast pre-equilibrium), which would otherwise render the enantiomeric outcome (ee value) independent

Structure and thermal stability of phosphorus-iodonium ylids

• Andrew Greener,
• Stephen P. Argent,
• Coby J. Clarke and
• Miriam L. O’Duill

Beilstein J. Org. Chem. 2024, 20, 2931–2939, doi:10.3762/bjoc.20.245

• phosphoranyl(aryl)iodonium compounds 1f–i, no direct correlation between the substituents’ Hammett parameter σp and the decomposition onset temperature Tonset was observed (Supporting Information File 1, Figure S13). However, the DSC thermograms of iodonium ylids with electron-poor aryl substituents (1h,i

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

• physicochemical descriptors. A prominent early example are Hammett parameters, developed in 1937 [26][27], that relate substituent parameters to the equilibrium constant of the deprotonation of a substituted benzoic acid. The derived substituent parameters are used to gain insight into the mechanism of reactions

• by observing the influence of substituents on a reaction outcome. However, Hammett parameters have shown to not fully describe observed trends. Therefore, complementary representations capturing other properties of a molecule have been derived (vide infra) [28]. While traditional linear free energy

• relationships such as those using Hammett parameters used linear models, the emergence of ML has led to the development of more complex algorithms, better suited for extracting hidden patterns in data. The ability of ML to efficiently capture complex relationships allows to extract influences on catalyst

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

• -diketones has been developed. The electron-withdrawing power of the heterocyclic substituent (which can be estimated on the basis of calculated Hammett constants) in the 1,3-diketone plays a pivotal role in the studied reaction. The series of meta-hetarylanilines prepared (21–85% isolated yield

• ) demonstrates the synthetic utility of the developed method. Keywords: aniline; benzannulation; condensation; 1,3-diketone; Hammett constants; terphenyl; Introduction The aniline moiety is omnipresent in the synthetic chemistry with applications ranging from building blocks to catalysis [1][2][3][4]. Among

• utilize Hammett constants. Since only a few numbers of experimentally measured Hammett constants for heterocycles are known [55][56], this approach seems unsuitable at first. However, recently, a web-based tool for the calculation of the substituent descriptors compatible with the Hammett sigma constants

Unraveling the role of prenyl side-chain interactions in stabilizing the secondary carbocation in the biosynthesis of variexenol B

• Moe Nakano,
• Rintaro Gemma and
• Hajime Sato

Beilstein J. Org. Chem. 2023, 19, 1503–1510, doi:10.3762/bjoc.19.107

• group. However, such a large conformational change is unlikely to occur within the enzyme. Therefore, the Curtin–Hammett principle is not applicable to this system. To investigate the details of carbocations and hyperconjugations in the variexenol B biosynthetic pathway, we carried out a bond length

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• these preferential outcomes is not understood, and may derive from rapidly equilibrating species (e.g., 2 and 3) reacting under Curtin–Hammett control, from hard/soft principles dictating the Lewis base’s selectivity with either the stronger (e.g., 3) or weaker (e.g., 2) σ-hole, or possibly from other

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

• geometrical or constitutional situation at the binding sites [92]. In a detailed recent study, the finding of a Hammett correlation in such nanorotors corroborated that a rate-determining dissociation at the rotator–metal binding interaction dictated the rotational speed [93]. Reducing Product Inhibition (RPI

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

• . The solvolyses of these additional types of sulfur(VI) substrates will be the topics of a future review. Keywords: correlation; Grunwald–Winstein equation; Hammett equation; mechanism; solvolysis; sulfonyl halides; Review 1. Introduction to solvolyses of sulfonyl halides In medicinal chemistry

• to synchronous bond-making and bond-breaking, with a small negative charge development on the sulfur at the transition state, for the solvolytic process. Subsequent to this 1927 study, Hammett reported [5][6] in 1937, the development of the Hammett equation, involving the consideration of a scale

• Hammett substituent values obtained can be applied to the solvolyses and other reactions of substrates varying only in the aromatic ring substituent that they carry, under otherwise identical conditions as regards solvent and temperature. Frequently, as in the reactions to be reviewed in this subsection

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• might better to compare the Hammett acidity function, H0, as this is more suitable for concentrated acids. On this scale triflic acid H0 = −14.1, perchloric acid H0 = −13, and sulfuric acid H0 = −12.0 are more similar and might explain why nitration conditions cause rearrangement [67]. Alternatively

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• science emphasizes focusing and prizes specialists over generalists. Nowadays, scientists "feed on one plant only", but their ancestors had a more varied diet. Zonation occurred rapidly in chemistry during the first decades of the 20th century, and Hammett, in the introduction of his Physical Organic

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

• accounting for the electron-donating or -withdrawing ability of substituents are of major importance in synthetic organic chemistry. The Hammett constant σ for a variety of substituents [18][19] and improved values, known as σ+, furnished by Brown et al. [20][21] – some of which are listed in Table 1 for

• solvolysis of aryl derivatives 13a–i to highlight the importance of the nature of the aromatic substituent on the solvolysis rate (Figure 2) [43]. As anticipated, a faster rate was observed for electron-donating groups, while electron-withdrawing groups slowed the process down. Plotting the Hammett–Brown

• obtained. Similarly, the nature of the aromatic substituent influenced the solvolysis rate, with an observed acceleration for substrates adorned with electron donor substituents and a deceleration for those carrying electron-withdrawing substituents. The Hammett–Brown correlation gave a straight line, with

Exploring the possibility of using fluorine-involved non-conjugated electron-withdrawing groups for thermally activated delayed fluorescence emitters by TD-DFT calculation

• Dongyang Chen and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2021, 17, 210–223, doi:10.3762/bjoc.17.21

• acceptors correlate linearly to the Hammett substituent constant, σp, (Figure 2c) [35]. All of these fluorinated acceptors are much weaker than the more commonly investigated benzonitrile (BN, −1.30 eV), triphenyltriazine (TRZ, −1.72 eV) and benzophenone (BP, −1.58 eV) acceptors. These results indicate that

• , b) Calculated HOMO, LUMO, S1 and T1 energies, as well as HOMO and LUMO topologies of BN, TRZ and BP (isovalue = 0.02). c) Hammett para substituent values (σp) relationship with the calculated LUMO energies for fluorine-containing acceptors PhCF3, PhOCF3, PhOSCF3, and PhSF5. Calculated HOMO, LUMO, S1

Benzothiazolium salts as reagents for the deoxygenative perfluoroalkylthiolation of alcohols

• Armin Ariamajd,
• Nils J. Gerwien,
• Benjamin Schwabe,
• Stefan Dix and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2021, 17, 83–88, doi:10.3762/bjoc.17.8

• trifluoromethylthio group (SCF3), for example, is attracting considerable attention due to its strong lipophilicity-enhancing influence (Hansch constant π = 1.44) and electron-withdrawing properties (Hammett constants σp = 0.50 and σm = 0.40) [7][8][9][10][11][12]. On the other hand, longer-chain perfluoroalkylthio

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

• diamagnetic (or the paramagnetic) species in the two photostationary states. The intermolecular association constants of pyridines as axial ligands to Ni-porphyrins as a function of their para substituents usually follow the Hammett relationship [5][12]. Hence, the association constants should also be

• File 1. “Record player” approach for molecular spin switching. a) General principle b) Variation of the substituent R in 4-position of the pyridine unit. Record player molecules synthesized in this work (1f–j) are highlighted. Hammett plot of the investigated pyridine substituents [36]. UV–vis spectra

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• ester. A common trend between mono- and difluorination was that increasing the electron-releasing ability of a substituent para to the benzylic position decreased the product yield. It is known that polarity matching effects are negligible for benzylic HAT and that BDEs do not correlate with Hammett

Natural dolomitic limestone-catalyzed synthesis of benzimidazoles, dihydropyrimidinones, and highly substituted pyridines under ultrasound irradiation

• Kumar Godugu,
• Venkata Divya Sri Yadala,
• Mohammad Khaja Mohinuddin Pinjari,
• Trivikram Reddy Gundala,
• Lakshmi Reddy Sanapareddy and
• Chinna Gangi Reddy Nallagondu

Beilstein J. Org. Chem. 2020, 16, 1881–1900, doi:10.3762/bjoc.16.156

• sedimentary rocks present in this area. Catalyst characterization The NDL catalyst was ground into a fine powder and then sieved in a 200-mesh sieve. The chemical composition of the catalyst was determined by standard quantitative analysis. The basic strength of the catalyst was analyzed by using Hammett

• indicators. The catalyst was characterized by XRD, IR, Raman, SEM, and EDAX analysis. The chemical composition of the NDL was determined by adopting a standard quantitative analysis [75]. The obtained results are summarized in Table 1. The basic strength of the NDL catalyst (H_) was measured using Hammett

• indicators, namely bromothymol blue (H_ = 7.2), phenolphthalein (H_ = 9.8), 2,4-dinitroaniline (H_ = 15.0), and nitroaniline (H_ = 18.4) as Hammett indicators. In each case, 5 mL of a methanolic solution of the Hammett indicator was added to 50 mg of the catalyst, shaken well, and then allowed to equilibrate

Models of necessity

• Timothy Clark and
• Martin G. Hicks

Beilstein J. Org. Chem. 2020, 16, 1649–1661, doi:10.3762/bjoc.16.137

• for calculating partial charges. Such methods, although seemingly outdated, are uniquely fast because of the limits in computer power when they were developed. Chematica [58] uses among other parameters the Hammett substituent constant [59] developed in the 1930s. These uses of group contribution

• ], developing a ML-suitable model for intermolecular interactions is feasible. As noted above, old models such as Gasteiger–Marsili [38][39] charges or Hammett constants [59] have been used in recent applications. This development ignores the immense improvements in hard- and software of the last four decades

Fluorohydration of alkynes via I(I)/I(III) catalysis

• Jessica Neufeld,
• Constantin G. Daniliuc and
• Ryan Gilmour

Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135

• substrate, a Hammett analysis was conducted. To that end, log(kR/kH) was plotted against the Hammett σ−p parameter for the para-substituted pentynyl benzoates with R = OMe, H, Cl, and NO2 (Figure 4A). However, the resulting slope of the Hammett plot was essentially zero (ρ ≈ 0). In contrast, a second

• Hammett analysis in which the substitution of the iodoarene catalyst was explored (R = Me, H, Cl, and Br) revealed a build-up of positive charge (ρ < 0) during the rate-determining step (Figure 4B). From a methodological perspective, this study provides a conceptual platform to unmask the valuable α

• Hammett analyses, have identified key determinants that are essential for reaction efficiency. X-ray crystal structure analysis of ketone 2 reveals a dihedral angle of φO=C-C-F = −3.7°. Although the origin of this specificity requires clarification, this fluorohydration reaction constitutes a rare case of

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• nature of the aromatic substituent within the trifluoroacetophenone component, followed by a ring opening with allylamine, showed that the introduction of electron-withdrawing groups (positive Hammett sigma constants) [56], such as p-bromo, p-fluoro, and p-trifluoromethyl groups, respectively, were well

Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles

• Ming-Xi Bi,
• Shuai Liu,
• Yangen Huang,
• Xiu-Hua Xu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2020, 16, 657–662, doi:10.3762/bjoc.16.62

• SCF3, 0.88 for CF3, and 0.61 for SMe) [1] that helps permeation across biological membranes. Furthermore, the strong electron-withdrawing properties of the SCF3 group (Hammett constants: σp = 0.50, σm = 0.40) [2] with respect to metabolic stability have attracted considerable interest in pharmaceutical

Palladium-catalyzed Sonogashira coupling reactions in γ-valerolactone-based ionic liquids

• László Orha,
• József M. Tukacs,
• László Kollár and
• László T. Mika

Beilstein J. Org. Chem. 2019, 15, 2907–2913, doi:10.3762/bjoc.15.284

• the 4-substituents, i.e., no Hammett-plot can be obtained for the above reaction, it can be stated that the rate determining step of the Sonogashira coupling is not related to the formation of Pd-aryl species. Subsequently, a series of different acetylenes, which can readily be dissolved in [TBP

A diastereoselective approach to axially chiral biaryls via electrochemically enabled cyclization cascade

• Hong Yan,
• Zhong-Yi Mao,
• Zhong-Wei Hou,
• Jinshuai Song and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2019, 15, 795–800, doi:10.3762/bjoc.15.76

• –Hammett scenario (Scheme 4) [42]. Specifically, the equilibrium of the conformations IV and IV′ is much faster than their respectively cyclizations to give V and V′. Since TS2 is relatively lower in energy than TS3, V is formed as the major product. Conclusion In summary, we have developed a

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• -position of the aromatic ring could contribute to the stabilization of TS1, in which the Ar–C3–C2–P dihedral angle is close to 0°, by considering the mesomeric form TS2. The observed dependence of the diastereoselectivity on the σ+ Hammett constant of the para substituents further supported the proposed

Bioinspired cobalt cubanes with tunable redox potentials for photocatalytic water oxidation and CO₂ reduction

• Zhishan Luo,
• Yidong Hou,
• Jinshui Zhang,
• Sibo Wang and
• Xinchen Wang

Beilstein J. Org. Chem. 2018, 14, 2331–2339, doi:10.3762/bjoc.14.208

• ., that the variation of the ligands has a profound effect on the observed redox potentials. Figure 3 displays the plots of the Hammett σp parameters for the ligands versus the half-wave potentials (E1/2) for 1-R complexes, and the potentials increase linearly as a function of σp, giving an indicator of

• the electronic influence of the substituents on E1/2. The E1/2 values for the complexes increase in the following order: 1-R, R = OMe < Me < H < Br < CN. The Hammett analysis provides a positive slope value, indicating that the E1/2 value is favored by electron-withdrawing ligands [48][55]. As the

• ligand becomes more electron withdrawing, the reduced electron density at the metal center makes the Co center in the complex easier to reduce and more difficult to oxidize [55]. Most surprisingly, the potentials could be predicted simply by considering the Hammett σp values. Therefore, the observed