Weak Electron-withdrawing Groups Research Articles

The Substituent Effects of Suzuki Coupling in Aqueous Micelles.

The Suzuki coupling in aqueous micelles has received much attention, but few attempts focus on its substituent effects. In view of the significant substituent effects on this reaction, it is necessary and practical to investigate its substituent effects. Herein, the substituent effects of Suzuki coupling in aqueous micelles are well established through Hammett plots and kinetic studies. In the cases of aryl halides, the rate-determining step of the reaction will shift from the oxidation addition step to the transmetalation step as the substituents' electron withdrawing ability increases, so aryl halides with weak electron-withdrawing groups exhibit better reactivity than ones containing strong electron-withdrawing or electron-donating groups. For arylboronic acids, the electron donating groups are beneficial to the Suzuki reaction, while the electron withdrawing group is unfavorable for the reaction. The Suzuki reactions of substituent exchange between arylboronic acids and aryl halides further confirm these substituent effects.

The oxidation of 2-phenyl ethanols by Fe(NO3)3·9H2O in CF3COOH: The dramatic substituent effect

2-Phenyl ethanol with various substituents on the phenyl ring was oxidized by Fe(NO3)3·9H2O in the present of trifluoroacetic acid (TFA) at 0°C to room temperature. The product was highly dependent on the electronic properties of the substituent. Weak electron-donating and electron-withdrawing groups (Such as CH3, Cl, Br, and F) afforded good to excellent yields (95 – 64 %) of the corresponding phenylacetic acids. Moderate electron-withdrawing groups (Such as CF3, COOH) resulted in ∼ 50 % yield of the corresponding phenylacetic acids. However, strong electron-withdrawing group (such as NO2 and CN) hindered the reaction, the corresponding phenethyl trifluoroacetate was acquired almost quantitatively. Furthermore, the strong electron-donating group of methoxy highly promoted the oxidation, resulted in nitrated benzaldehydes and benzoic acids in relative low yields.

Acceptor molecules with different central and terminal units for P3HT based solar cells: Effects of the molecular structures on their properties

The design strategy of acceptor materials matched with poly(3-hexylthiophene) (P3HT) is highly desired for the development of low-cost organic solar cells (OSCs). Herein, we introduced strong electron-donating central units and weak electron-withdrawing end groups to construct the acceptors with high HOMO and LUMO, modulated the molecular symmetry and conjugation length by changing the structures of central units, and synthesized six acceptor molecules, namely, TDTC-O2F, TTDTC-O2F, TTTDTC-O2F, TDTC-ThBr, TTDTC-ThBr and TTTDTC-ThBr. The high LUMO energy level of the acceptors endowed the P3HT based OSCs with relatively high Voc values. Molecular symmetry, conjugation length of central units and the terminal structure jointly affect the molecular crystallinity and miscibility of the blends. Owing to the proper film morphology, the P3HT:TTDTC-ThBr based devices achieved the champion power conversion efficiency of 6.15 %.

Bisphenol a modification and how its structure influences human serum albumin binding force

Bisphenol A (BPA) is an environmental hormone with substantial physiological toxicity to the human body. Three electron-withdrawing derivatives of BPA are synthesized in this study to reduce its toxicity. The interaction mechanism between BPA and its three derivatives with human serum albumin (HSA) is investigated using molecular docking, electrochemistry, circular dichroism spectrum analysis, and fluorescence spectroscopy. Temperature-dependent tests and time-resolved fluorescence spectra reveal that all four compounds dynamically quench the internal fluorescence of HSA. Based on molecular docking and site competition outcomes, four compounds are primarily bound to site I's active pocket. Thermodynamic parameters indicate that the compounds’ interaction with HSA is spontaneous, and introducing weak electron-withdrawing groups changes the action force. Circular dichroism and synchronous fluorescence measurements suggest four compounds impact HSA's structure. The substituents' electron attraction capacity determines their impact. Electrochemical studies examine the effect of electron-absorbing groups on the BPA and HSA binding capacity. Pharmacokinetics showed that nitro-substituted BPA may be a potential superior substitute for BPA. These results indicate crucial practical value, providing theoretical support for future research.

Computational Investigations of Reaction Mechanisms and Transformation Products of Olefins with Hypochlorous Acid.

Hypochlorous acid (HOCl) as the main component in chlorination and also as the innate immune factor relevant to immune defense has attracted considerable attention. Electrophilic addition reaction of olefins with HOCl, one of the most important prototype of chemical reactions, has been intensively studied for a long time; however, it has not been fully understood yet. In this study, addition reaction mechanisms and transformation products of model olefins with HOCl were systematically investigated by the density functional theory method. The results indicate that the traditionally believed stepwise mechanism with a chloronium-ion intermediate is only suitable for olefins substituted with electron-donating groups (EDGs) and weak electron-withdrawing groups (EWGs) but it is a carbon-cation intermediate that is favorable for EDGs featuring p-π or π-π conjugation with the C═C moiety. Moreover, olefins substituted with moderate or/and strong EWGs prefer the concerted and nucleophilic addition mechanisms, respectively. Epoxide and truncated aldehyde as the main transformation products can be generated from chlorohydrin through a series of reactions involving hypochlorite; however, their generation is kinetically not as feasible as the formation of chlorohydrin. The reactivity of three chlorinating agents (HOCl, Cl2O, and Cl2) and the case study of chlorination and degradation of cinnamic acid were also explored. Additionally, APT charge on the double-bond moiety in olefin and energy gap (ΔE) between the highest occupied molecular orbital (HOMO) energy of olefin and the lowest unoccupied molecular orbital (LUMO) energy of HOCl were found to be good parameters to distinguish the regioselectivity of chlorohydrin and reactivity of olefin, respectively. The findings of this work are helpful in further understanding the chlorination reactions of unsaturated compounds and identifying complicated transformation products.

Preformed Pd(II) Catalysts Based on Monoanionic [N,O] Ligands for Suzuki-Miyaura Cross-Coupling at Low Temperature

This paper describes the synthesis and catalytic testing of a palladium complex with a 5-membered chelating [N,O] ligand, derived from the condensation of 2,6-diisopropylphenyl aniline and maple lactone. This catalyst was active towards the Suzuki-Miyaura cross-coupling reaction, and its activity was optimised through the selection of base, solvent, catalytic loading and temperature. The optimised conditions are mild, occurring at room temperature and over a short timescale (1 h) using solvents considered to be ‘green’. A substrate scope was then carried out in which the catalyst showed good activity towards aryl bromides with electron-withdrawing groups. The catalyst was active across a broad scope of electron-donating and high-withdrawing aryl bromides with the highest activity shown for weak electron-withdrawing groups. The catalyst also showed good activity across a range of boronic acids and pinacol esters with even boronic acids featuring strong electron-withdrawing groups showing some activity. The catalyst was also a capable catalyst for the cross-coupling of aryl chlorides and phenylboronic acid. This more challenging reaction requires slightly elevated temperatures over a longer timescale but is still considered mild compared to similar examples in the literature.

A Comparative Study on the Oxidation Mechanisms of Substituted Phenolic Pollutants by Ferrate(VI) through Experiments and Density Functional Theory Calculations.

In this work, the oxidation of five phenolic contaminants by ferrate(VI) was comparatively investigated to explore the possible reaction mechanisms by combined experimental results and theoretical calculations. The second-order rate constants were positively correlated with the energy of the highest occupied molecular orbital. Considering electronic effects of different substituents, the easy oxidation of phenols by ferrate(VI) could be ranked as the electron-donating group (-R) > weak electron-withdrawing group (-X) > strong electron-withdrawing group (-(C═O)-). The contributions of reactive species (Fe(VI), Fe(V)/(IV), and •OH) were determined, and Fe(VI) was found to dominate the reaction process. Four main reaction mechanisms including single-oxygen transfer (SOT), double-oxygen transfer (DOT), •OH attack, and electron-transfer-mediated coupling reaction were proposed for the ferrate(VI) oxidation process. According to density functional theory calculation results, the presence of -(C═O)- was more conducive for the occurrence of DOT and •OH attack reactions than -R and -X, while the tendency of SOT for different substituents was -R > -(C═O)- > -X and that of e--transfer reaction was -R > -X > -(C═O)-. Moreover, the DOT pathway was found in the oxidation of all four substituted phenols, indicating that it may be a common reaction mechanism during the ferrate(VI) oxidation of phenolic compounds.

Selective complexation of trivalent americium over europium with substituted Triazolebipyridine-based ligand in high Level-Liquid Waste- A DFT Investigation

Similar chemical properties like ionic radius and oxidation states exhibited by trivalent actinides (An(III)) and lanthanides (Ln(III)) pose a challenge for their separation in reprocessing of spent nuclear fuel. For this purpose, we explore the 6,6′-bis(1-(2-ethylhexyl)-1H-1,2,3-triazol-4-yl)-2,2′-bipyridine (EH-BTzBP) ligand from a theoretical perspective aiming to tune its selectivity through substitutions. The effect of strong, moderate, and weak electron-withdrawing groups (EWGs) on the selectivity of the ligand has been studied using scalar relativistic quantum chemistry calculations. The results reveal that among the four ligating nitrogen atoms, nitrogen on triazole rings contribute more to the complexation compared to the other two nitrogens of bipyridyl (bpy) moiety. According to the quantum theory of atoms in molecules (QTAIM) analysis, Eu complexes show bifurcate interactions between the nitrogen atom of ligand and oxygen of metal nitrate, while such bonds are absent in Am complexes. The EWGs have been identified to enhance the selectivity of the EH-BTzBP ligand in general and nitro group in particular, to show exceptional selectivity towards Am(III) over Eu(III). Our study could render new insights in understanding the effect of EWGs in tuning the selectivity of Bis-1,2,3-triazolebipyridine derivatives and pave the way for designing substituted ligands with better selectivity for the separation process.

Tracking the Transition from Pericyclic to Pseudopericyclic Reaction Mechanisms Using Multicenter Electron Delocalization Analysis: The [1,3] Sigmatropic Rearrangement.

Herein, the power of multicenter electron delocalization analysis to elucidate the intricacies of concerted reaction mechanisms is brought to light by tracking the transition of [1,3] sigmatropic rearrangements from the high-barrier pericyclic mechanism in 1-butene to the barrierless pseudopericyclic mechanism in 1,2-diamino-1-nitrosooxyethane. This transition has been progressively achieved by substituting the migrating group, changing the donor and acceptor atoms, and functionalizing the alkene unit with weak and strong electron-donating and electron-withdrawing groups. Fourteen [1,3] sigmatropic reactions with electronic energy barriers ranging from 1 to 89 kcal/mol have been investigated. A very good correlation has been found between the barrier and the four-center electron delocalization at the transition state, the latter calculated for the atoms involved in the four-centered ring adduct formed along the reaction path. Surprisingly, the barrier has been found to be independent of the bond strength between the migrating group and the donor atom so that only the changes induced in the multicenter bonding control the kinetics of the reaction. Additional insights into the effect of atom substitution and group functionalization have also been extracted from the analysis of the multicenter electron delocalization profiles along the reaction path and qualitatively supported by the topological analysis of the electron density.

A DFT mechanistic study on oxidative dehydrogenative Diels–Alder reaction of alkylbenzenes

Cross-dehydrogenative Diels-Alder cycloaddition reaction between readily-available alkyl benzenes and electron-deficient dienophiles is an attractive synthetic route to access carbocyclic compounds which have high utility in the chemical and pharmaceutical industries. This work reports a study at the M06-2X/6-311G(d) and M06-2X/6–311++G(d,p) levels of theory on the reaction of alkyl benzenes with electron-deficient dienophiles in the presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as an oxidant and hydroquinone as an activator, so as to understand the chemoselectivity of the reaction (addition across the alkene functionality versus the ketone functionality), the role of the activator, the effects of substituents and the effect of solvent on the reaction. The results show the addition of the alkene bonds of methylstyrene across the alkene functionality of the electron-deficient dienophiles has generally low barriers compared to the addition across the carbonyl functionality of the electron-deficient dienophile. Powerful electron-withdrawing group (cyano) on the electron-deficient dienophile decrease the energy barrier for the cycloaddition and decrease the stability of the product whiles weak electron-withdrawing (bromine and chlorine) and electron-donating groups increase the energy barrier for the cycloaddition and decrease the stability of the product. The hydroquinone as an activator decreases the activation barrier for the Diels-Alder cycloaddition reaction.

Modulating mechanism of N[sbnd]H-based excited-state intramolecular proton transfer by electron-withdrawing substituent at aromatic para-position

Using TDDFT method, modulating mechanism of NH-based excited-state intramolecular proton transfer by electron-withdrawing substituent cyano at the aromatic para-position of four 2-(2′-aminophenyl) benzothiazole compounds have been demonstrated at B3LYP/6-311+G(d, p)/IEFPCM theory level. The scanned potential energy curves reveal that introduction of a strong electron-withdrawing group tosyl at the amino nitrogen can remarkably facilitate the occurrence of the ESIPT reaction, whereas introduction of a weak electron-withdrawing group acetyl at the amino nitrogen or introduction of an electron-withdrawing cyano group on the benzene ring at the para-position with respect to the amino group can contribute to the ESIPT process in certain degree.

5,6,7,8-Tetrahydronaphthalen-1-amine as Precursor for Thiazolidi­nones and Benzothiazepinones: Synthesis and Atropisomeric Relationship

The one-pot reaction of 5,6,7,8-tetrahydronaphthalen-1-amine, mercaptoacetic acid, and arenealdehydes having strong and weak electron-withdrawing groups gave the corresponding 1,3-thiazolidin-4-ones (47–70%). When arenealdehydes bearing strong and weak electron-donating groups were used as precursors, the 1,4-benzothiazepin-2-ones were obtained (30–72%) by p-TsOH catalysis. All compounds are unknown and were characterized by GC-MS and NMR techniques, and available crystals by X-ray diffraction studies. The atropisomerism phenomenon was observed in several 1,3-thiazolidin-4-ones as confirmed by VTNMR method. The Tc was established as 332 K and the energy required for the interconversion of one atrop­isomer into another is around 16.8 kcal·mol–1. Chemical quantum calculation and NOESY displayed that more stable isomer has the tetrahydro­naphthalene portion below the five-ring plane. Only a small difference between isomers (–0.21 to –0.84 kcal·mol–1) was observed by calculated energy.

Novel salicylanilides from 4,5-dihalogenated salicylic acids: Synthesis, antimicrobial activity and cytotoxicity

Salicylanilides have proved their activity against tuberculosis (TB). One weak electron-withdrawing substituent is favored at the salicylic part, specially Cl or Br atoms at positions 4 or 5. On the other hand, the antimycobacterial activity of salicylanilides is negatively affected when a strong electron-withdrawing substituent (NO2) is present at the same positions. Herein we describe the synthesis and characterization of novel salicylanilides possessing two weak electron-withdrawing groups (halogen atoms) at their salicylic part and compare their antitubercular activity with their monohalogenated analogues. All dihalogenated derivatives proved to possess antitubercular activity at a very narrow micromolar range (MIC=1–4μM), similar with their most active monohalogenated analogues. More importantly, the most active final molecules were further screened against multidrug resistant strains and found to inhibit their growth at the range of 0.5–4μM.

Syntheses of trifluoroethylated unsymmetrical 1,3-diynes by using 1,1-dichloro-2,2,2-trifluoroethane

Copper-mediated reaction of terminal 1,3-diynes with 1,1-dichloro-2,2,2-trifluoroethane (CF3CHCl2) using ethanolamine as ligand gave trifluoroethylated unsymmetrical 1,3-diynes in moderate to good yields. The reaction were carried out under mild conditions, and were easy to operate. Aryl groups with weak electron-withdrawing group or electron-donating group, and alkyl substitutents at terminal 1,3-diynes were tolerated. Synthesis of a trifluoroethylated conjugated triyne by using this method was demonstrated. Further transformation of the trifluoroethylated unsymmetrical 1,3-diyne to provide trifluoroethyl-substituted 1,2,3-triazole and isoxazole as application examples were successfully realized.

Structure and cytotoxic activity of terpenoid-like chalcones

Compounds with either ionone or chalcone skeletons present many biological properties including anticancer activity. Here we have prepared eight terpenoid-like chalcones in order to assess whether hybrid compounds with both structural frameworks could exhibit enhanced pharmacological profile. The terpenoid-like chalcones were synthesized by means of Claisen–Schmidt condensation reaction, using either α- or β-ionone with substituted benzaldehydes. The structure of six derivatives was elucidated by single crystal X-ray diffraction technique for the first time. Cyclohexene ring adopts half-chair conformation in α-ionone-derived chalcone with quaternary carbon at the flap, while twist puckering was observed in β-ionone terpenoid-like chalcones. All prepared compounds were tested for their cytotoxic activity against three cancer cell lines, namely SF-295, HCT-116 and OVCAR-8, which allowed us to establish some structure–activity relationships. Terpenoid-like chalcones with nitro substituted phenyl rings, regardless of its position and ionone type, were the most active chalcones among all that tested. The IC50 values do also reveal a trend of decrease in cytotoxic activity with weak electron-withdrawing groups at phenyl ring.

Influence of substituents on the nature of metal⋯π interaction and its cooperativity with halogen bond.

High-level quantum chemical calculations have been performed to investigate the influence of substituents on the metal-π interaction and its cooperative effect with halogen bond in C2X4⋯MCN⋯ClF (X = H, CN, CH3; M = Cu, Ag, Au). The strong electron-withdrawing group CN weakens the metal-π covalent interaction, while the weak electron-withdrawing group CH3 strengthens it. The metal-π covalent interaction is dominated by electrostatic energy although the AuCN complex has approximately equal electrostatic and polarization contributions. However, the metal-π covalent interaction is governed by polarization energy due to the CN substitution. A cooperative effect is found for the halogen bond and metal-π interactions in C2H4⋯MCN⋯ClF, while a diminutive effect occurs in the triads by the CN substituent. Orbital interaction analysis indicates that the strong electron-withdrawing group CN causes the C=C group vary from a stronger donor orbital to a stronger acceptor orbital.

ChemInform Abstract: Highly Selective Electrochemical Fluorination of Dithioacetal Derivatives Bearing Electron‐Withdrawing Substituents at the Position α to the Sulfur Atom Using Poly(HF) Salts.

Anodic fluorination of dithioacetals bearing electron-withdrawing ester, acetyl, amide, and nitrile groups at their α-positions was comparatively studied using various supporting poly(HF) salts like Et3N·nHF (n = 3–5) and Et4NF·nHF (n = 3–5). In the former two cases, the corresponding α-fluorination products or fluorodesulfurization products were obtained selectively depending on supporting poly(HF) salts used. In sharp contrast, in the latter two cases, fluorination product selectivity was strongly affected by the electron-withdrawing ability of α-substituents: A dithioacetal bearing a relatively weak electron-withdrawing amide group provided a fluorodesulfurization product selectively while a dithioacetal having a strongly electron-withdrawing nitrile group gave the α-fluorination product predominantly regardless of the poly(HF) salts used.

Highly selective electrochemical fluorination of dithioacetal derivatives bearing electron-withdrawing substituents at the position α to the sulfur atom using poly(HF) salts.

Anodic fluorination of dithioacetals bearing electron-withdrawing ester, acetyl, amide, and nitrile groups at their α-positions was comparatively studied using various supporting poly(HF) salts like Et3N·nHF (n = 3–5) and Et4NF·nHF (n = 3–5). In the former two cases, the corresponding α-fluorination products or fluorodesulfurization products were obtained selectively depending on supporting poly(HF) salts used. In sharp contrast, in the latter two cases, fluorination product selectivity was strongly affected by the electron-withdrawing ability of α-substituents: A dithioacetal bearing a relatively weak electron-withdrawing amide group provided a fluorodesulfurization product selectively while a dithioacetal having a strongly electron-withdrawing nitrile group gave the α-fluorination product predominantly regardless of the poly(HF) salts used.

Preparation and Performance of Hydroxypropyl Methylcellulose Esters of Substituted Succinates for in Vitro Supersaturation of a Crystalline Hydrophobic Drug

We prepared hydroxypropyl methylcellulose (HPMC) esters of substituted succinates and examined their performance for improving the aqueous solubility of crystalline hydrophobic drugs in spray-dried dispersions (SDDs). From one HPMC, we synthesized five HPMC esters using various monosubstituted succinic anhydrides. These HPMC esters along with a commercial HPMC acetate succinate (HPMCAS) were spray-dried from solutions with phenytoin. The SDDs with different matrices at 10 wt % loading had very similar bulk properties with a minimal amount of detectable crystalline phenytoin as revealed by scanning electron microscopy (SEM), powder X-ray diffraction (powder XRD), and differential scanning calorimetry (DSC). In solution, while the SDD with HPMCAS was very effective at achieving high levels of phenytoin supersaturation initially, it was not competent at maintaining such supersaturation due to the rapid crystallization of the dissolved phenytoin. Alternatively, SDDs with several synthesized HPMC esters of substituted succinates not only achieved rather high initial supersaturation but also maintained high concentrations for extended time (i.e., 1.5 h and longer). Such maintenance was largely ascribed to the inhibition of phenytoin nucleation. Structure-property relationships were established, and the most successful systems contained a high degree of substitution and a combination of a thioether with neighboring weak electron-withdrawing groups in the substituted succinic anhydrides. The effective maintenance of supersaturated solutions was only found in SDDs with rather low drug loadings, which indicates the significance of sufficiently high concentrations of polymer additives in the dissolution media.

Synthesis of novel bis(β-aminocarbonyl) compounds and some β-aminocarbonyls by catalyst-free multicomponent Mannich reactions

A highly diastereoselective catalyst-free multicomponent Mannich reaction between cyclohexanone, aromatic aldehydes and amines in cyclohexane is described. The double Mannich reaction of diamines and two equivalents of aldehydes and cyclohexanone gave the novel bis(β-aminocarbonyl) compounds. Reactions proceeded in good to high yields with an excellent diastereoselectivity. The best selectivity was obtained where there are weak electron donating and electron-withdrawing groups on the aldehyde. The rate formation of Mannich product is decreased when strong electron-withdrawing groups and/or electron-releasing groups are present on aldehyde. In these cases only the corresponding imines are obtained in moderate to high yields. Aromatic diamines are more suitable than aliphatic diamines in this reaction. Usually, aliphatic diamines only produce the corresponding imines albeit in high yields. .