Continuous flow synthesis of azobenzenes via Baeyer–Mills reaction

• Jan H. Griwatz,
• Anne Kunz and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2022, 18, 781–787, doi:10.3762/bjoc.18.78

• only the geometry is altered from the planar (E)-AB to its twisted (Z)-AB form, but also its properties change (e.g., dipole moment and polarity) [13][14]. Furthermore, the (Z)-AB can be reversibly switched back by visible light or thermally [15]. To synthesize ABs a variety of reactions can be chosen

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• find that the diastereoselectivity of this reaction was not very good. Because the polarity of the two diastereoisomers were very similar, it was very difficult to isolate them as pure compounds by column chromatography. For convenience, only the pure major diastereoisomers of the spiro compounds 3a–w

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

• -withdrawing substituents present in the 1,3-diketones would increase the degree of enolization of the 1,3-diketones [30][33], and the polarity of the solvent would have only a little effect on the keto–enol tautomerization of such 1,3-diketones [30]. During our studies, we also observed the effect of solvent

• 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

• enol tautomer of the 1,3-diketone was predominant in CDCl3, while the keto tautomer was predominant in methanol-d4, which is a more polar solvent than CDCl3 (Figure 7). Our observations thus reinforce Meyer’s rule [34][35], which states that the keto tautomer is favored as the solvent polarity

Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures

• Sangram Gore,
• Sundarababu Baskaran and
• Burkhard König

Beilstein J. Org. Chem. 2022, 18, 331–336, doi:10.3762/bjoc.18.37

• replacement of organic solvents. The melts are stable against air and have very low vapor pressures resembling the properties of ionic liquids. In addition, the polarity of these melts is very high [33]. Recently, we have explored several organic transformations such as coupling reaction, cycloaddition

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• , and factors like steric and electronic effects of the nucleophile and substrate and the polarity of the solvent would influence the product ratio [75]. Here, as illustrated above, the authors introduced the cage host J as the noncovalent protecting group of the internal reactive sites, which directed

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• realised by increasing the flow rate of the thiosulphate solution to remove sufficient DMSO in view of satisfactory separation being achieved. Due to the high polarity of the reaction mixture, moderately non-polar chromatographic conditions were required (3% EtOAc, 97% cyclohexane at start), with a

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• neuraminidase in relation to the analogues bearing hydrophobic substituents and ca. 5% for more polar substituents. These results suggest that polarity changes are less tolerated by neuraminidase due to the big difference in impact of hydrophobicity upon inhibition, thus indicating a simple approach to

• hydrophobicity is important to inhibition of neuraminidase as the most potent compounds possess hydrophobic aromatic substituents. Conversely, increase in polarity results in weak inhibition (ca. 5%) as noted for compounds bearing substituents with nitrogen or a hydroxy group (3d–g). In fact, the higher polarity

• consensus that may lead to a simple approach to differentiate TcTS and neuraminidase inhibitory activity as a polarity change seems to be less tolerated by the latter. This intriguing result is difficult to explain since all sialidases share a very similar catalytic domain, despite low sequence similarity

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• polarity solvents, of a novel class of diametric phosphine gold(I) cavitands characterized by a 1,2,3-alternate geometry. Preliminary catalytic studies were performed on a model cycloisomerization of 1,6-enynes as a function of the relative orientation of the bonded gold(I) nuclei with respect to the

• low polarity solvents, is dominated by the 1,2,3-alternate conformation assumed by the DN intermediate, as previously demonstrated in our recent contributions [33][34]. Hence, the most notable features of 1H NMR for A(AuCl)2 are represented by a pattern for the methylene bridging protons in a 1:1:1

• 1,6-enynes. Conclusion We reported the synthesis of a novel family of diametric diphosphine gold(I) complexes whose geometry in low-polarity solvents is controlled by the 1,2,3-alternate conformation of the calix[6]arene precursor. These catalysts are able to tune the selectivity of catalytic

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

• derivative. It was proposed that these observations constituted good evidence for the incursion of an SN1 pathway. A subsequent study by Vizgert and Savchuk [15] concentrated on the effect of gradually increasing the polarity of the solvent on going from 70% dioxane to 100% H2O. It was proposed that the rate

• of acceleration in aqueous dioxane when hydroxide ion was added. As the polarity of the medium is increased, so also is the solvent ionizing power (Y) and the ionization pathway could become of increasing importance and eventually dominant. Forbes and Maskill, first in a communication [26] and then

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

• ). Solvatochromic studies for DICzTRZ show that the PDM of the ground state structure is small and so the absorption spectrum is essentially not affected by changes in polarity, while the excited state shows the characteristic positive solvatochromism associated with an emission from a CT state (λPL going from 462

• incorporating DICzTRZ as the emitter in a solution-processed OLED, we next investigated the photophysical behavior of this compound in solid host matrices. We began with 10 wt % doped film of DICzTRZ in PMMA as the polarity of PMMA emulates well that of toluene [36]. The emission maximum in PMMA is 514 nm

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• substituent or polarity of the solvent (behavior in CHCl3, MeOH, and DMSO is quite similar). Notably, one can highlight compound 3bb (R = Ph, R1 = 5-NEt2) which transitions vary significantly with the change in polarity of the medium (4–24 nm), and this may be due to the donor diethylamino group attached to

• the 400–550 nm region depending on the solvent polarity (CHCl3, DMSO, and MeOH). Therefore, it is possible to infer that the polarity of the solvents directly influences the electronic transitions in the excited state, with significant changes for the compound in more polar and protic solvents, by

• revealed significant differences, mainly according to the change in solvent polarity, being, for example, higher for compounds in DMSO and MeOH than in chloroform solution. Furthermore, the highest values were found in the presence of electron-donating groups, i.e., in compounds 3bb (R = Ph, R1 = 5-NEt2

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• nickel catalysis is also often employed to C(sp3)‒H alkylation transformations. For example, in 2017, MacMillan and co-workers reported a selective C(sp3)–H alkylation protocol via polarity-matched hydrogen atom transfer (HAT) using photoredox and nickel catalysis [85]. This method works through

• vinylation/C‒H arylation of cyclic oxalates. Proposed mechanism for the mpg-CN/nickel photocatalytic C(sp3)–H arylation. Proposed mechanism for photoredox nickel-catalyzed C(sp3)–H alkylation via polarity-matched HAT. Proposed mechanism for the CzIPN and nickel-catalyzed C(sp3)‒H alkylation of ethers

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

• ideal chemical components for the generation of smart devices. Depending on the polymer structure, including backbone and functional groups [10], their properties can be reversibly influenced by external chemical (e.g., pH value [11][12], ionic strength [13], polarity of solvent [14]), biological (e.g

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• solubility of Cs2CO3 in toluene and 1,4-dioxane [24]. Using K2CO3 in MeCN, Longworth et al. have obtained 10 with a similar degree of N-1 regioselectivity (ratio N-1:N-2 = 2.8:1) [26]. However, altering solvent polarity when employing 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as a base (Table 1, entries 15–17

2,4-Bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridines: synthesis and photophysical properties

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli,
• Noureddine Chaaben,
• Kamel Alimi,
• Stefan Jopp and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 1629–1640, doi:10.3762/bjoc.17.115

• polarity difference. In fact, derivative 4f shows the highest dipole moment of 4.276 D as compared to 4a (0.698 D). As shown in Table 5, the ionization potential (IP) and electron affinity (EA) of tetrahydroacridines are almost identical. In addition, EHOMO and ELUMO do not change notably and the

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• absorption maximum (λmax) was observed at 230 nm for 3ac in DMSO (Figure 3, left side). The fluorescence studies carried out for 3ac in four different solvents revealed that the emission maxima shifted bathochromically by almost 40 nm upon changing the solvent polarity, for instance, from non-polar hexane to

A new glance at the chemosphere of macroalgal–bacterial interactions: In situ profiling of metabolites in symbiosis by mass spectrometry

• Marine Vallet,
• Filip Kaftan,
• Veit Grabe,
• Fatemeh Ghaderiardakani,
• Simona Fenizia,
• Aleš Svatoš,
• Georg Pohnert and
• Thomas Wichard

Beilstein J. Org. Chem. 2021, 17, 1313–1322, doi:10.3762/bjoc.17.91

• single Ulva individuals were targeted visually and ablated with a laser spot size of approximately 10 μm in positive and negative polarity in a mass range from m/z 100 to m/z 1000. The other parameters stayed like for the MSI mode. In profiling, the same area of the rhizoid and the tip of the thallus of

• Ulva samples. In the late exponential stage, bacterial monoculture was recovered from agar plates with a 10 µL loop and diluted in 100 µL of sterile water. Five microliters of the solution were spotted onto a glass slide and analysed in AP-SMALDI-HRMS mode in positive and negative polarity. The data

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• . Furthermore, it usually displays a high polarity and consequently good aqueous solubility. These features render biguanides an attractive chemical function in medicinal chemistry, where it tends to establish as a valuable pharmacophore for drug discovery. Currently, seven biguanide drugs are commercially

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• enantioselectivity varied with the polarity of the solvent. The optimization study disclosed that the enantioselectivity increases with the decrease of the polarity of the solvent (Scheme 68). Yu and co-workers reported a novel segment-coupling Prins cyclization involving sequential benzylic/allylic C–H bond

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent

• Ke Wu,
• Yichen Ling,
• An Ding,
• Liqun Jin,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69

• the LR upon thio-substitution [11][12][13]. It has been observed that the polarity of compound A is generally similar to the desired products, thus making the purification of the desired products by extraction operations less efficient. Therefore, the purification is rather difficult and usually a

• separation by careful column chromatography is necessary because of both the similar polarity and the stoichiometric amount of the formed compound A. With regard to this, the use of LR was always limited to small-scale preparations [6][8]. Other than the exploration of potential surrogates of LR for the

• temperature and a new spot with a much higher polarity was observed on the TLC plate. With a mixed solvent of ethyl acetate/petroleum ether 1:3 as the eluent, the Rf of compound A was around 0.5, while the Rf of the newly generated compound was at around 0.05 either from MeOH or EtOH treatment. Later, the new

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

• containing fluorine have been particularly well characterized for their use as spectroscopic probes, mainly in 19F NMR applications [12][13][14][15]. It is typical that the incorporation of fluorine into certain molecular fragments changes the local polarity as well as the electronic and conformational

• based on the recognition of fluoroprolines by the native enzyme aminoacyl-tRNA synthetase (vide infra) proves this assumption. 2.2 Local polarity Another important feature of fluoroprolines is their local electrostatic potential (local polarity). In proline, position 4 contains a positive surface

• Lipophilicity The impact of fluorine substitution on the global polarity of the molecule is another parameter that should be considered. The global polarity can be typically analyzed by measurements of the molecular partitioning, e.g., the lipophilicity index logP. For aliphatic organofluorine compounds, this

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• biocatalyzed process for the tagging of residual benzyl alcohol. Initially the removal of benzyl alcohol proved challenging due to its high boiling point (205 °C) and its co-polarity with many of the carbamate products. As this rendered evaporation and column chromatography ineffective, an alternative approach

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

• solvolysis rate for derivatives 13f or 13g and the solvent polarity parameter YOTs [45]. The solvent participation in the solvolysis of these tertiary benzylic tosylates was thus defined as “unimportant” by the authors. Gassman and Harrington successfully measured the solvolysis kinetics of CF3-substituted

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• product, but purification and isolation of the product by column chromatography was not possible ‒ neither with conventional nor with reversed phase methods. It turned out that the high polarity of the triol complicated its separation from other polar side products. To circumvent this problem, we decided