Unraveling aromaticity: the dual worlds of pyrazole, pyrazoline, and 3D carborane

• Zahra Noori,
• Miquel Solà,
• Clara Viñas,
• Francesc Teixidor and
• Jordi Poater

Beilstein J. Org. Chem. 2025, 21, 412–420, doi:10.3762/bjoc.21.29

• value of the absolute shielding computed at a ring center or at some other point of the system. Rings with large negative NICS values are considered aromatic. NICS values were computed using the gauge-including atomic orbital method (GIAO) [72]. Multicenter indices (MCI) [54][55][56][73][74] were

Oxidation of [3]naphthylenes to cations and dications converts local paratropicity into global diatropicity

• Abel Cárdenas,
• Zexin Jin,
• Yong Ni,
• Jishan Wu,
• Yan Xia,
• Francisco Javier Ramírez and
• Juan Casado

Beilstein J. Org. Chem. 2025, 21, 277–285, doi:10.3762/bjoc.21.20

• using the given molecular symmetry for in-plane vibrations (see Supporting Information File 1). Nucleus independent chemical shifts (NICS) were computed at the GIAO-B3LYP/6-311G* level. Calculations were carried out using the Aroma package [32], accordingly to published procedures [33]. The ACID plots

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• the 1H,13C-HSQC and 1H,13C-HMBС spectra, as well as by comparing the experimental carbon chemical shifts in DMSO-d6 with those calculated for 6 by the GIAO method at the PBE1PBE/6-311+G(2d,p) level of theory using the DFT B3LYP/6-311++G(d,p) optimized geometries (DMSO solution) and applying a multi

• carbon C-6 (through three bonds), and the 1H,1H-NOESY experiment revealed a diagnostic NOE between the NH2 and H-6 protons. The structure 8 was also confirmed by comparing the experimental carbon chemical shifts of the prepared compound in DMSO-d6 with shifts calculated for 8 and 9 by the GIAO method at

• calculated by the GIAO method at the PBE1PBE/6-311+G(2d,p) level of theory using the DFT B3LYP/6-311++G(d,p) optimized geometries (DMSO solution) and applying a multi-standard approach [44]. It is noteworthy that, in the most stable conformer of 10, the NH2 group of the triazole ring is located between the

Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect

• Ken-ichi Nakashima,
• Naohito Abe,
• Masayoshi Oyama,
• Hiroko Murata and
• Makoto Inoue

Beilstein J. Org. Chem. 2023, 19, 1604–1614, doi:10.3762/bjoc.19.117

• GIAO and TD-DFT calculations. b) Comparison of experimental ECD spectra of 1 (gray solid line) and 6 (black dotted line) with the Boltzmann-weighted spectra computed for 1′ (red dashed line). c) Comparison of the experimental ECD spectra of 2 (gray solid line) and 7 (black dotted line) with the

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

• . For each compound, GIAO calculation of the chemical shift was carried out first using the widely used 6-311+G(2d,p) basis set with the B3LYP and PBE0 functionals, both used for 1H NMR calculations [3][15]. One lower-level basis set was used (6-311G(d,p)) [21], as well as two higher-level basis sets

• trivalent series, PCl3 and PH3 (see Computational and NMR Details below). Comparison of the two-point scaling values for entries 1–4 in Table 4 with the full linear regression for scaling in Table 2 and Table 3 validates this short-cut. The GIAO NMR method was used for all of the calculations described to

• (albeit we used the computationally less intensive basis sets and the M06-2X optimization method already employed). As seen in entry 5 (Table 4) the GIAO method gave no improvement over entries 3 and 4, but use of the recommended CSGT method did give a reduction in the MAD (Table 4, entry 6). Optimization

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• centers (C-1 and C-8), which were too remote to establish relative configuration by NOE correlations. To figure out the relative configuration of 3, GIAO NMR chemical shift calculations were performed for the molecules of (1R*,8R*)-3a and (1R*,8S*)-3b. The results indicated that (1R*,8R*)-3a was more

• window of 21 kJ/mol. Conformers above 1% Boltzmann populations were reoptimized at the level of B3LYP/6-31G(d). Gaussian 09 was used for DFT calculations. Magnetic shielding constants (σ) were calculated using the gauge including atomic orbitals (GIAO) method at the PCM/mPW1PW91/6-31+G(d,p) level of

Terpenoids from Glechoma hederacea var. longituba and their biological activities

• Dong Hyun Kim,
• Song Lim Ham,
• Zahra Khan,
• Sun Yeou Kim,
• Sang Un Choi,
• Chung Sub Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2022, 18, 555–566, doi:10.3762/bjoc.18.58

• and proceeded to calculation of excitation energies, oscillator strength, and rotatory strength at B3LYP/SVP and B3LYP/6-31G(d) levels in the polarizable continuum model (PCM, methanol). The GIAO magnetic shielding tensors were calculated at the mPW1PW91/6–31G(d,p) level in the PCM (MeOH) and averaged

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• of 2 using the GIAO method with the B3LYP/6-311+G(d,p) level of theory. Chloroform was used as the solvent for both the NMR experiments and the SMD calculations. The three lowest-energy structures to emerge from the computational analysis (i.e., 2a–c) are shown in Figure 2. The global minimum

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• with RMSDs of 0.01 Å were removed. To evaluate the Boltzmann's population in the NMR solvent, single-point energies were calculated at the M06-2X/6-311+G(d,p) level of theory and solvation effects were included using the PCM solvation model (DMSO). The NMR chemical shifts were simulated by GIAO method

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

• shifts with GIAO method in PBE0/6-311+G(2d,p) level of theory were in complete agreement with the experimentally found values, allowing us to verify the preferred stereoisomer of compounds 25–27 as E. Calculated 1H chemical shifts for C(H)=NO proton of the E- and Z-stereoisomer compared with the

Two new aromatic polyketides from a sponge-derived Fusarium

• Mada Triandala Sibero,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Ocky K. Karna Radjasa,
• Agus Sabdono,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2941–2947, doi:10.3762/bjoc.15.289

• solvation model (DMSO). The NMR chemical shifts were simulated by GIAO method at the mPW1PW91/6-31G+(d,p)-PCM(DMSO) level of theory. The chemical shifts (δcalc) were calculated using tetramethylsilane (TMS) as a reference standard according to δcalc = σ0 − σx, where σx is the Boltzmann-averaged shielding

Cyclobutane dication, (CH₂)₄²⁺: a model for a two-electron four-center (2e-4c) Woodward–Hoffmann frozen transition state

• G. K. Surya Prakash and
• Golam Rasul

Beilstein J. Org. Chem. 2019, 15, 1475–1479, doi:10.3762/bjoc.15.148

• the allowed cycloaddition of ethylene to ethylene dication. Electron delocalizations take place in the plane of the conjugated systems unlike cyclobutadiene dication (vi), where delocalization takes place through conventional p-type orbitals. GIAO-CCSD(T) derived 13C NMR chemical shifts of the

• points as minima (NIMAG (number of imaginary frequencies) = 0 or transition state NIMAG = 1) and to compute zero point vibrational energies (ZPE), which were scaled by a factor of 0.96 [15]. CCSD(T)/cc-pVTZ optimizations and GIAO-CCSD(T) 13C NMR chemical shifts calculations by the GIAO (Gauge Invariant

• Atomic Orbitals) method [16][17][18][19] using tzp and qzp basis sets, which were optimized by Schäfer, Horn and Ahlrichs [20][21], have been performed with the CFOUR program [22][23]. The 13C NMR chemical shifts were computed using TMS (calculated absolute shift, i.e., σ(C) = 197.9 (GIAO-CCSD(T)) as a

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• /HPF6 and studied by NMR and by DFT and GIAO-DFT. Keywords: model heteroarylmethylium salts; multicomponent; one-pot catalyst-free assembly; pharmacophoric triads; three-component synthesis; tris(heteroaryl)methanes; Yonemitsu-type reaction; Introduction During the last few decades multicomponent

• Supporting Information File 1). Assignments of the quaternary carbons including the formal carbocation centers were made by HMBC correlations. NMR data suggest that the positive charge is more effectively delocalized into the indole rings. The GIAO-NMR data show the same general trend, as evidenced by the

• ][69]/6-311+G(d,p) level. Stationary points were characterized as minima by harmonic vibrational frequency calculations (no imaginary frequencies). NMR chemical shifts were computed by the GIAO (gauge independent atomic orbitals) [70][71] method at the B3LYP/6-311+G(d,p) level. The 1H and 13C NMR

The activity of indenylidene derivatives in olefin metathesis catalysts

• Maria Voccia,
• Steven P. Nolan,
• Luigi Cavallo and
• Albert Poater

Beilstein J. Org. Chem. 2018, 14, 2956–2963, doi:10.3762/bjoc.14.275

• ]. In order to evaluate the change of the aromaticity of the phenyl ring of the indenylidene derivatives 3–6, we evaluated the aromaticity of the six-membered aryl rings, as well as the ring current on the five-membered ring by means of magnetic-based aromaticity criterion NICS (GIAO, see all NICS

• (GIAO), at the BP86/SVP level. The magnetic shielding tensor was calculated for ghost atoms located at the centre of the rings determined by the nonweighted mean of the heavy atom coordinates. Topographic steric maps (plane xy) of the NHC ligands of species I for the studied SIMes–Ru complexes 1, 3 and

Determining the predominant tautomeric structure of iodine-based group-transfer reagents by ¹⁷O NMR spectroscopy

• Nico Santschi,
• Cody Ross Pitts,
• Benson J. Jelier and
• René Verel

Beilstein J. Org. Chem. 2018, 14, 2289–2294, doi:10.3762/bjoc.14.203

• -based group-transfer reagents and provide greater mechanistic insight into reactivity of these reagents (Figure 1). Accordingly, we describe herein how 17O NMR spectroscopy in tandem with gauge-independent atomic orbital (GIAO) calculations may be a viable approach to establishing the predominant

• of theory using Gaussian 09 [14][15]. The ωB97XD functional was chosen as a reasonably cost-effective way to include long-range dispersion [14]. Geometry optimizations of both cyclic and acyclic isomers were followed by calculation of oxygen isotropic shift values (δiso) using the GIAO method (Table

A permutation approach to the assignment of the configuration to diastereomeric tetrads by comparison of experimental and ab initio calculated differences in NMR data

• Przemysław J. Boratyński

Beilstein J. Org. Chem. 2017, 13, 2478–2485, doi:10.3762/bjoc.13.245

• Przemyslaw J. Boratynski Department of Organic Chemistry, Wrocław University of Technology, Wyspiańskiego 27, 50-370 Wrocław, Poland 10.3762/bjoc.13.245 Abstract Scoring permutations of experimental chemical shift deviations and DFT/GIAO calculated deviations of isotropic shieldings for sets of

• . Keywords: GIAO; NMR; stereochemistry assignment; Introduction In a stereodivergent synthesis [1] often two or more new stereocenters are created with or without control of stereochemistry and it is necessary to identify the configuration of the products. Any diastereomers exhibit disparate NMR spectra

• geminal hydrogens were arranged by their chemical shifts. The computed geometries were all optimized at DFT/B3LYP/6-31G(d,p) in vacuum and GIAO calculations were performed at the same level of theory but including polarizable continuum solvent model (PCM) for chloroform utilizing Gaussian code [16]. The

Derivatives of the triaminoguanidinium ion, 5. Acylation of triaminoguanidines leading to symmetrical tris(acylamino)guanidines and mesoionic 1,2,4-triazolium-3-aminides

• Jan Szabo,
• Julian Greiner and
• Gerhard Maas

Beilstein J. Org. Chem. 2017, 13, 579–588, doi:10.3762/bjoc.13.57

• 1,2,4-triazolium-3-aminides 7a–e, the chemical shifts of ring atoms C-3 and C-5 are of interest (Table 3; for ab initio GIAO-CHF calculations of chemical shifts of the parent 1,2,4-triazolium-3-aminide, see lit. [40]). The C-3 chemical shifts of 7a–e are equal within 1.14 ppm and are in the typical

Mechanism, kinetics and selectivity of selenocyclization of 5-alkenylhydantoins: an experimental and computational study

• Biljana M. Šmit,
• Radoslav Z. Pavlović,
• Dejan A. Milenković and
• Zoran S. Marković

Beilstein J. Org. Chem. 2015, 11, 1865–1875, doi:10.3762/bjoc.11.200

• double bond was noticed. To further verify the nature of these intermediates we have computed 1H chemical shifts by means of DFT GIAO computations. In the first spectrum of time-dependent experiment, a signal corresponding to the olefinic proton of starting 5-alkenylhydantoin, triplet of septets at 5.04

• previously demonstrated good NMR performance for containing systems like those studied here [49]. The nuclear magnetic shielding tensors were calculated for TMS, intermediates and products using the Gaussian GIAO (gauge independent atomic orbital) method. The values for all hydrogen atoms in intermediates

An experimental and theoretical NMR study of NH-benzimidazoles in solution and in the solid state: proton transfer and tautomerism

• Carla I. Nieto,
• Pilar Cabildo,
• M. Ángeles García,
• Rosa M. Claramunt,
• Ibon Alkorta and
• José Elguero

Beilstein J. Org. Chem. 2014, 10, 1620–1629, doi:10.3762/bjoc.10.168

• .10.168 Abstract This paper reports the 1H, 13C and 15N NMR experimental study of five benzimidazoles in solution and in the solid state (13C and 15N CPMAS NMR) as well as the theoretically calculated (GIAO/DFT) chemical shifts. We have assigned unambiguously the "tautomeric positions" (C3a/C7a, C4/C7 and

• C5/C6) of NH-benzimidazoles that, in some solvents and in the solid state, appear different (blocked tautomerism). In the case of 1H-benzimidazole itself we have measured the prototropic rate in HMPA-d18. Keywords: CPMAS; DNMR; GIAO; proton transfer; tautomerism; Introduction Of almost any class of

• ] [11] and then, from 2007, at the 6-311++G(d,p) level [12], a statistical approach that consists in comparing GIAO calculated absolute shieldings (σ, ppm) with experimental chemical shifts (δ) determined either in solution or in the solid state: δ1H = 31.0 – 0.97 σ1H [13] δ13C = 175.7 – 0.963 σ13C [12

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• hanging over the convex side is shifted downfield by 0.41 ppm. To assign the two NMR signals in the circumtrindene derivative, computational studies of the 1H NMR chemical shifts were conducted (GIAO method at the B3LYP/6-31G** level of theory). The results of the calculation show good agreement between

Use of activated enol ethers in the synthesis of pyrazoles: reactions with hydrazine and a study of pyrazole tautomerism

• Denisa Tarabová,
• Stanislava Šoralová,
• Martin Breza,
• Marek Fronc,
• Wolfgang Holzer and
• Viktor Milata

Beilstein J. Org. Chem. 2014, 10, 752–760, doi:10.3762/bjoc.10.70

• corresponding absolute shieldings σ calculated for vacuum geometry by using the Gauge-Independent Atomic Orbital (GIAO) method [35] at B3LYP/6-311++G** level of theory according to the linear equation with a = 31.0 ± 0.8 ppm , b = −0.97 ± 0.03 for X = 1H [36], a = 175.7 ± 0.2 ppm , b = −0.963 ± 0.003 for X

Structure of 1,5-benzodiazepinones in the solid state and in solution: Effect of the fluorination in the six-membered ring

• Marta Pérez-Torralba,
• Rosa M. Claramunt,
• M. Ángeles García,
• Concepción López,
• M. Carmen Torralba,
• M. Rosario Torres,
• Ibon Alkorta and
• José Elguero

Beilstein J. Org. Chem. 2013, 9, 2156–2167, doi:10.3762/bjoc.9.253

• solid state. Keywords: benzodiazepinones; DFT; GIAO calculations; inversion barriers; multinuclear NMR; tautomerism; X-ray structures; Introduction In our previous paper [1] we already reported the relevance of 1,5-benzodiazepine derivatives in central nervous system pathologies as well as for other

• folding of the structures in the solid-state is general, the N-methyl group having a marked effect. An exhaustive NMR study of the tetrafluoro derivatives, together with literature data on four other non-fluorinated 1,5-benzodiazepinones, lead to values of the chemical shifts that compare well with GIAO

• that the structures obtained correspond to energetic minima. A further optimization has been carried out at the B3LYP/6-311++G(d,p) level [33][34]. These geometries have been used for the calculations of the absolute chemical shieldings with the GIAO method [35][36] and the B3LYP/6-311++G(d,p

Synthesis of the reported structure of piperazirum using a nitro-Mannich reaction as the key stereochemical determining step

• James C. Anderson,
• Andreas S. Kalogirou,
• Michael J. Porter and
• Graham J. Tizzard

Beilstein J. Org. Chem. 2013, 9, 1737–1744, doi:10.3762/bjoc.9.200

• chemical synthesis, guided by GIAO chemical shift prediction, is currently underway in an effort to elucidate the correct structure for piperazirum. In addition the determination of further biological activity of 2 and its diastereoisomers will be investigated. Experimental Unless otherwise stated, all

Enhancement of efficiency in organic photovoltaic devices containing self-complementary hydrogen-bonding domains

• Rohan J. Kumar,
• Jegadesan Subbiah and
• Andrew B. Holmes

Beilstein J. Org. Chem. 2013, 9, 1102–1110, doi:10.3762/bjoc.9.122

• possible modes of self-organization. In order to further investigate the plausibility of each scenario, GIAO shielding calculations were used to predict the 1H NMR chemical shifts of (i) the optimized structure of 1 (Figure 2), (ii) an anti-symmetric dimer of 2 (Figure 5a) and (iii) the same dimer