Nucleophilic Solvent Research Articles

Anion-π interaction with alkenes: persistent complexes vs. irreversible reactions of anions with tetracyanoethylene.

The interaction of the tetracyanoethylene (TCNE) π-acceptor with oxo- and fluoro-anions (BF4-, PF6-, ClO4-, NO3-) led to the formation of anion-π complexes in which these polyatomic anions were located over the face of alkenes, with multiple contacts being shorter than the van der Waals separations. The anion-π associations of TCNE with halides were delimited by the electron-donor strengths and nucleophilicity of the anions. Specifically, while bromides formed persistent anion-π associations with TCNE in the solid state and in solutions, only transient anion-π complexes with iodides and chlorides were observed. In the case of iodide (strong 1e reducing agent), the formation of anion-π complexes was followed by the reduction of the π-acceptor to the TCNE-˙ anion-radical. The interaction of TCNE with Cl- (and F-) anions (which are better nucleophiles in the aprotic solvents) led to the formation of 1,1,2,3,3-pentacyanoprop-2-en-1-ide anions. Thermodynamics, UV-Vis spectra, and structures, as well as contributions of electrostatics, orbital interactions, and dispersion to the interaction energies in the complexes of TCNE with various anions were closely related to the characteristics of the corresponding associations with the aromatic and p-benzoquinone acceptors. This points out the general equivalence of the interactions in the anion-π complexes with different π-acceptors and the critical role of the nature of the anions in these bindings.

Aryl carbonyls and carbinols as proelectrophiles for Friedel-Crafts benzylation and alkylation.

Friedel-Crafts benzylation/alkylation using benzylic, tertiary, and homobenzylic alcohols; aryl aldehydes, aryl ketones, and the highly challenging aryl carboxylic acids and esters as proelectrophiles has been achieved using borane-ammonia and TiCl4, greatly broadening the scope of useable substrates. Incorporation of deactivated aromatic proelectrophiles and specificity for substitution at the benzylic position are demonstrated in the synthesis of various di- and triarylalkane products. Dual protocols allow for the use of standard nucleophilic solvents (benzene, toluene, etc.) or for stoichiometric addition of more valuable nucleophiles including furans, thiophenes, and benzodioxoles.

Exploring borderline SN1-SN2 mechanisms: the role of explicit solvation protocols in the DFT investigation of isopropyl chloride.

Nucleophilic substitution at saturated carbon is a crucial class of organic reactions, playing a pivotal role in various chemical transformations that yield valuable compounds for society. Despite the well-established SN1 and SN2 mechanisms, secondary substrates, particularly in solvolysis reactions, often exhibit a borderline pathway. A molecular-level understanding of these processes is fundamental for developing more efficient chemical transformations. Typically, quantum-chemical simulations of the solvent medium combine explicit and implicit solvation methods. The configuration of explicit molecules can be defined through top-down approaches, such as Monte Carlo (MC) calculations for generating initial configurations, and bottom-up methods that involve user-dependent protocols to add solvent molecules around the substrate. Herein, we investigated the borderline mechanism of the hydrolysis of a secondary substrate, isopropyl chloride (iPrCl), at DFT-M06-2X/aug-cc-pVDZ level, employing explicit and explicit + implicit protocols. Top-down and bottom-up approaches were employed to generate substrate-solvent complexes of varying number (n = 1, 3, 5, 7, 9, and 12) and configurations of H2O molecules. Our findings consistently reveal that regardless of the solvation approach, the hydrolysis of iPrCl follows a loose-SN2-like mechanism with nucleophilic solvent assistance. Increasing the water cluster around the substrate in most cases led to reaction barriers of ΔH‡ ≈ 21 kcal mol-1, with nine water molecules from MC configurations sufficient to describe the reaction. The More O'Ferrall-Jencks plot demonstrates an SN1-like character for all transition state structures, showing a clear merged profile. The fragmentation activation strain analyses indicate that energy barriers are predominantly controlled by solvent-substrate interactions, supported by the leaving group stabilization assessed through CHELPG atomic charges.

A Formal γ-C-H Functionalization of Carboxylic Acids Guided by Metal-Nitrenoids as an Unprecedented Mechanistic Motif.

Harnessing the key intermediates in metal-catalyzed reactions is one of the most essential strategies in the development of selective organic transformations. The nitrogen group transfer reactivity of metal-nitrenoids to ubiquitous C-H bonds allows for diverse C-N bond formation to furnish synthetically valuable aminated products. In this study, we present an unprecedented reactivity of iridium and ruthenium nitrenoids to generate remote carbocation intermediates, which subsequently undergo nucleophile incorporation, thus developing a formal γ-C-H functionalization of carboxylic acids. Mechanistic investigations elucidated a unique singlet metal-nitrenoid reactivity to initiate an abstraction of γ-hydride to form the carbocation intermediate that eventually reacts with a broad range of carbon, nitrogen, and oxygen nucleophiles, as well as biorelevant molecules. Alternatively, the same intermediate can lead to deprotonation to afford β,γ-unsaturated amides in a less nucleophilic solvent.

Lewis Acid Promoted Vicinal Oxytrifluoromethylselenolation of Alkenes.

Herein, we have developed a metal-free, Lewis acid promoted vicinal oxytrifluoromethylselenolation of alkenes using trifluoromethyl selenoxides as electrophilic trifluoromethylselenolation reagents and alcohols as nucleophiles. With less steric and good nucleophilic solvents (such as ethanol and methol), Tf2O-catalyzed oxytrifluoromethylselenolation could be realized, while stoichiometric Tf2O was required to promote full transformation with less nucleophilic and steric solvents (such as isopropanol and tert-butanol). The reaction featured good substrate scope, functional group compatibility, and diastereoselectivity. This method could be further applied to oxytrifluoromethylselenolation, aminotrifluoromethylselenolation with stoichiometric nucleophiles under modified conditions. A mechanism involving a seleniranium ion was proposed based on the preliminary results.

The salicylate 1,2-dioxygenase from Pseudaminobacter salicylatoxidans DSM 6986T is a bifunctional enzyme that inactivates the mycotoxin ochratoxin A by a novel amidohydrolase activity

The salicylate 1,2-dioxygenase from the bacterium Pseudaminobacter salicylatoxidans DSM 6986T (PsSDO) is a versatile metalloenzyme that participates in the aerobic biodegradation of aromatic compounds, such as gentisates and salicylates. Surprisingly, and unrelated to this metabolic role, it has been reported that PsSDO may transform the mycotoxin ochratoxin A (OTA), a molecule that appears in numerous food products that results in serious biotechnological concern. In this work, we show that PsSDO, together with its dioxygenase activity, behaves as an amidohydrolase with a marked specificity for substrates containing a C-terminal phenylalanine residue, similar to OTA, although its presence is not an absolute requirement. This side chain would establish aromatic stacking interactions with the indole ring of Trp104. PsSDO hydrolysed the amide bond of OTA rendering the much less toxic ochratoxin α and L-β-phenylalanine. The binding mode of OTA and of a diverse set of synthetic carboxypeptidase substrates these substrates have been characterized by molecular docking simulations, which has permitted us to propose a catalytic mechanism of hydrolysis by PsSDO that, similarly to metallocarboxypeptidases, assumes a water-induced pathway following a general acid/base mechanism in which the side chain of Glu82 would provide the solvent nucleophilicity required for the enzymatic reaction. Since the PsSDO chromosomal region, absent in other Pseudaminobacter strains, contained a set of genes present in conjugative plasmids, it could have been acquired by horizontal gene transfer, probably from a Celeribacter strain.

Detailed Understanding of Solvent Effects for the Cationic Ring-Opening Polymerization of 2-Ethyl-2-oxazoline

Polymerization of 2-ethyl-2-oxazoline (EtOx) has often been in the spotlight for fundamental studies of poly(2-alkyl/aryl-2-oxazoline)s (PAOx) polymerization, especially initiator screening, solvent screening, and copolymerization trends. In this work, we build on previous observations of solvent effects on the cationic ring-opening polymerization (CROP) of EtOx, with additional experimental observations of previously unreported solvents to expand the explored parameter space. Our objective is to find solvents with the lowest activation energy (Ea) and higher Arrhenius preexponential factor (A), which will allow us to produce narrow molar mass distributions at higher molecular weights, in the least time. To achieve this, we examined the various single factors like Dimroth ET(30) values, the Kamlet–Abraham–Taft (KAT) linear free-energy relationship (LFER) equation(s), and the Catalan LFER equations. Only one of Catalan’s equations sufficiently disentangled dipolarity and polarizability to give a good fit due to contradictory effects. It was found that solvent nucleophilicity, electrophilicity, and polarizability affected the Ea, but not dipolarity. All four factors affected the A. This indicates that the Ea is minimized in solvents that do not solvate ions well (i.e. force ion-pairing), and A was minimized in more dipolar solvents that solvate the polymer chains well. A strongly negative activation entropy (ΔS‡) shows that the propagation reaction is associative. The Catalan LFER allows for the prediction of Ea, A, ΔH‡, and ΔS‡, and the derived kp, across a broad range of solvents.

One-Pot Tandem Alcoholysis-Hydrogenation of Polylactic Acid to 1,2-Propanediol.

The chemical recycling of end-of-life polylactic acid (PLA) plays roles in mitigating environmental pressure and developing circular economy. In this regard, one-pot tandem alcoholysis and hydrogenation of PLA was carried out to produce 1,2-propanediol, which is a bulk chemical in polymer chemistry. In more detail, the commercially available Raney Co was employed as the catalyst, and transformation was conducted in ethanol, which acted as nucleophilic reagent and solvent. Single-factor analysis and Box-Behnken design were used to optimize the reaction conditions. Under the optimized condition, three kinds of PLA materials were subjected to degradation. Additionally, 74.8 ± 5.5%, 76.5 ± 6.2%, and 71.4 ± 5.7% of 1,2-propanediol was yielded from PLA powder, particle, and straws, respectively, which provided a recycle protocol to convert polylactic acid waste into value-added chemicals.

Tetrahydroquinolinone derivatives exert antiproliferative effect on lung cancer cells through apoptosis induction

The anticancer properties of quinolones is a topic of interest among researchers in the scientific world. Because these compounds do not cause side effects, unlike the commonly used cytostatics, they are considered a promising source of new anticancer drugs. In this work, we designed a brief synthetic pathway and obtained a series of novel 8-phenyltetrahydroquinolinone derivatives functionalized with benzyl-type moieties at position 3. The compounds were synthesized via classical reactions such as nucleophilic substitution, solvent lysis, and condensation. Biological evaluation revealed that 3-(1-naphthylmethyl)-4-phenyl-5,6,7,8-tetrahydro-1H-quinolin-2-one (4a) exhibited potent cytotoxicity toward colon (HTC-116) and lung (A549) cancer cell lines. Analysis of the mechanism of action of compounds showed that compound 4a induced cell cycle arrest at the G2/M phase, leading to apoptotic cell death via intrinsic and extrinsic pathways. Taken together, the findings of the study suggest that tetrahydroquinolinone derivatives bearing a carbonyl group at position 2 could be potential lead compounds to develop anticancer agents for the treatment of lung cancers.

Uncovering the Synchronous Role of Bis‐borane with Nucleophilic Solvent as Frustrated Lewis Pair in Metal‐Free Catalytic Dehydrogenation of Ammonia‐borane**

AbstractMetal free catalysis has emerged as a viable alternative for transition metal based catalysts for enabling different chemical processes, particularly for de/hydrogenation reactions. Herein, employing theoretical studies we reveal the unexpected Frustrated Lewis Pair like reactivity of a boron based catalyst, 9,10‐dichlorodiboraanthracene and the ethereal solvent to enable dehydrogenation of ammonia‐borane (NH3BH3, AB) under moderate conditions. The mechanistic channels thus uncovered reveal that the boron catalyst abstracts a hydride from NH3BH3 followed by crucial stabilization of the NH3BH2+ moiety by the nucleophilic action of the solvent. H2 is released by the combination of hydride and proton from the borohydride moiety and the solvated NH3BH2+ respectively. Catalysis becomes unfeasible if the Lewis base‐like action of the ethereal solvent is not taken into consideration. Thus, it is suggested that the clandestine partnership of the Lewis Acid, Boron catalyst and the Lewis Base, ethereal solvent, i. e. FLP like action enables dehydrogenation of NH3BH3 in the instant case.

Quantum Defects: What Pairs with the Aryl Group When Bonding to the sp2 Carbon Lattice of Single-Wall Carbon Nanotubes?

Aryl diazonium reactions are widely used to covalently modify graphitic electrodes and low-dimensional carbon materials, including the recent creation of organic color centers (OCCs) on single-wall carbon nanotube semiconductors. However, due to the experimental difficulties in resolving small functional groups over extensive carbon lattices, a basic question until now remains unanswered: what group, if any, is pairing with the aryl sp3 defect when breaking a C═C bond on the sp2 carbon lattice? Here, we show that water plays an unexpected role in completing the diazonium reaction with carbon nanotubes involving chlorosulfonic acid, acting as a nucleophilic agent that contributes -OH as the pairing group. By simply replacing water with other nucleophilic solvents, we find it is possible to create OCCs that feature an entirely new series of pairing groups, including -OCH3, -OC2H5, -OC3H7, -i-OC3H7, and -NH2, which allows us to systematically tailor the defect pairs and the optical properties of the resulting color centers. Enabled by these pairing groups, we further achieved the synthesis of OCCs with sterically bulky pairs that exhibit high purity defect photoluminescence effectively covering both the second near-infrared window and the telecom wavelengths. Our studies further suggest that these diazonium reactions proceed through the formation of carbocations in chlorosulfonic acid, rather than a radical mechanism that typically occurs in aqueous solutions. These findings uncover the unknown half of the sp3 defect pairs and provide a synthetic approach to control these defect color centers for quantum information, imaging, and sensing.

Direct Observation of the Dynamics of Ylide Solvation by Hydrogen-bond Donors Using Time-Resolved Infrared Spectroscopy.

The photoexcitation of α-diazocarbonyl compounds produces singlet carbene intermediates that react with nucleophilic solvent molecules to form ylides. The zwitterionic nature of these newly formed ylides induces rapid changes in their interactions with the surrounding solvent. Here, ultrafast time-resolved infrared absorption spectroscopy is used to study the ylide-forming reactions of singlet carbene intermediates from the 270 nm photoexcitation of ethyl diazoacetate in various solvents and the changes in the subsequent ylide–solvent interactions. The results provide direct spectroscopic observation of the competition between ylide formation and C–H insertion in reactions of the singlet carbene with nucleophilic solvent molecules. We further report the specific solvation dynamics of the tetrahydrofuran (THF)-derived ylide (with a characteristic IR absorption band at 1636 cm–1) by various hydrogen-bond donors and the coordination by lithium cations. Hydrogen-bonded ylide bands shift to a lower wavenumber by −19 cm–1 for interactions with ethanol, −14 cm–1 for chloroform, −10 cm–1 for dichloromethane, −9 cm–1 for acetonitrile or cyclohexane, and −16 cm–1 for Li+ coordination, allowing the time evolution of the ylide–solvent interactions to be tracked. The hydrogen-bonded ylide bands grow with rate coefficients that are close to the diffusional limit. We further characterize the specific interactions of ethanol with the THF-derived ylide using quantum chemical (MP2) calculations and DFT-based atom-centered density matrix propagation trajectories, which show preferential coordination to the α-carbonyl group. This coordination alters the hybridization character of the ylidic carbon atom, with the greatest change toward sp2 character found for lithium-ion coordination.

Synthesis, Characterizations and Applications of Fluoroazaphosphatranes.

Haloazaphosphatranes are the halogenated parents of proazaphosphatranes, also known as Verkade's superbase. While the synthesis of iodo-, bromo- and chloroazaphosphatranes was reported more than thirty years ago by J. G. Verkade, the first synthesis of fluoroazaphosphatranes was only described in 2018 by Stephan et al. Currently, no common and versatile procedure exists to access fluoroazaphosphatranes platform with different structural characteristics. In this report, a new and simple synthesis of this class of compounds was developed based on the nucleophilic attack of the fluoride anion on chloroazaphosphatrane derivatives with good to high isolated yields for the corresponding fluoroazaphosphatranes (70-92%). The scope of the reaction was widened to fluoroazaphosphatranes bearing various substituents and X-ray molecular structures of two of them are reported. The stability of fluoroazaphosphatranes toward nucleophilic solvents like water has been investigated. As they revealed much more robust cations than their chloroazaphosphatrane parents, their chloride salts were tested as organocatalysts for the formation of cyclic carbonates from epoxides and CO2 . Fluoroazaphosphatranes proved to be both efficient and stable catalytic systems for CO2 conversion with catalytic activities similar to those of azaphosphatranes, and no decomposition of the cation was observed at the end of reaction.

Mapping transition state structures for thiophosphinoyl group transfer between oxyanionic nucleophiles in water and aqueous ethanol solvents

Thiophosphinoyl transfer between oxyanionic nucleophiles is associative in ethanol and concerted in water, with loose concerted TS in water-ethanol solvents.

Reactivity of a Carene-Derived Hydroxynitrate in Mixed Organic/Aqueous Matrices: Applying Synthetic Chemistry to Product Identification and Mechanistic Implications

β-hydroxynitrates (HN) are a major class of products formed during OH and NO3 initiated oxidation of terpenes. Their production contributes significantly to secondary organic aerosol (SOA) formation and NOx sequestration. However, studying the condensed phase reactions of this important class of molecules has been hindered by the lack of commercially available authentic standards. The goal of this work was to examine the influence of water concentration and solvent identity on product yields of a tertiary HN derived from 3-carene prepared in house. To assess the role of water on conversion chemistry, bulk-phase reactions were conducted in DMSO-d6, a non-nucleophilic solvent, with a gradient of water concentrations, and analyzed with 1H NMR. Product identifications were made by comparison with authentic standards prepared in house. Four major products were identified, including an unexpected diol produced from carbocation rearrangement, diol diastereomers, and trans-3-carene oxide, with varying yields as a function of water concentration. Product yields were also measured in two protic, nucleophilic solvents, MeOD-d4 and EtOD-d6. Finally, reactions with added chloride formed alkyl chloride products in yields approaching 30%. These results are among the first to highlight the complexities of nucleophilic reactions of hydroxynitrates in bulk, mixed aqueous/organic media and to identify new, unexpected products.

Synthesis of Polysilazane by Ammonolysis of Dichlorosilane in a Nucleophilic Solvent

Synthesis of Polysilazane by Ammonolysis of Dichlorosilane in a Nucleophilic Solvent

Rate and Product Studies with 1-Adamantyl Chlorothioformate under Solvolytic Conditions.

A study was carried out on the solvolysis of 1-adamantyl chlorothioformate (1-AdSCOCl, 1) in hydroxylic solvents. The rate constants of the solvolysis of 1 were well correlated using the Grunwald–Winstein equation in all of the 20 solvents (R = 0.985). The solvolyses of 1 were analyzed as the following two competing reactions: the solvolysis ionization pathway through the intermediate (1-AdSCO)+ (carboxylium ion) stabilized by the loss of chloride ions due to nucleophilic solvation and the solvolysis–decomposition pathway through the intermediate 1-Ad+Cl− ion pairs (carbocation) with the loss of carbonyl sulfide. In addition, the rate constants (kexp) for the solvolysis of 1 were separated into k1-Ad+Cl− and k1-AdSCO+Cl− through a product study and applied to the Grunwald–Winstein equation to obtain the sensitivity (m-value) to change in solvent ionizing power. For binary hydroxylic solvents, the selectivities (S) for the formation of solvolysis products were very similar to those of the 1-adamantyl derivatives discussed previously. The kinetic solvent isotope effects (KSIEs), salt effects and activation parameters for the solvolyses of 1 were also determined. These observations are compared with those previously reported for the solvolyses of 1-adamantyl chloroformate (1-AdOCOCl, 2). The reasons for change in reaction channels are discussed in terms of the gas-phase stabilities of acylium ions calculated using Gaussian 03.

Catecholase-like activity in 2D MOFs: Oxidation of 3,5-DTBC by two Cu(II) 2D MOFs of reduced Schiff base ligands

Two-dimensional metal-organic frameworks (2D MOFs) materials have been explored extensively for their interesting properties and applications, but not so much for Catecholase-like catalytic activity. We describe here two Cu(II) 2D MOFs of reduced Schiff base ligands for their Catecholase-like activity. These were synthesized and characterized by spectroscopic analyses. The solid state structure of [Cu2(NglyR)2] (where NglyR is a reduced Shiff base ligand derived from 2-hydroxy-1-naphthaldehyde and glycine) (1) consistes of two Cu(II) atoms bridged by two phenalato groups and further chelated by oxygen and nitrogen atoms of the glycine part of NglyR ligand. These dimers are further linked by the terminal carboxylato oxygen atoms to possess a 2D sheet structure. In the absence of solid-state structure of [Cu2(NSchR)2] (2) (where NSchR is a reduced Schiff base ligand derived from 2-hydroxy-1-naphthaldehyde and 1-amino-1-cyclohexanecarboxylic acid), the dinuclear core with bridging phenolate ligands has been proposed from physicochemical and spectroscopic methods. The MOFs have also been investigated for their catecholase-like activities with 3,5-di-tert-butylcatechol (3,5-DTBC). Hyperbolic inhibition was observed for 1 in the following solvent systems: MeOH, MeOH:DMF (95:5, v/v) and (90:10, v/v), but not for 2. Moreover, catalytic activities are found to be heavily influenced by v/v ratio of the mixed solvent systems and solvent nucleophilicity.

Nucleophilicity Prediction via Multivariate Linear Regression Analysis.

The concept of nucleophilicity is at the basis of most transformations in chemistry. Understanding and predicting the relative reactivity of different nucleophiles is therefore of paramount importance. Mayr’s nucleophilicity scale likely represents the most complete collection of reactivity data, which currently includes over 1200 nucleophiles. Several attempts have been made to theoretically predict Mayr’s nucleophilicity parameters N based on calculation of molecular properties, but a general model accounting for different classes of nucleophiles could not be obtained so far. We herein show that multivariate linear regression analysis is a suitable tool for obtaining a simple model predicting N for virtually any class of nucleophiles in different solvents for a set of 341 data points. The key descriptors of the model were found to account for the proton affinity, solvation energies, and sterics.

Properties of the tert-butyl halide solvolysis transition states.

We have obtained properties (or descriptors) of the transition states in the solvolysis of tert-butyl chloride, bromide and iodide. We show that all three transition states, in both protic and in aprotic solvents, are highly dipolar and are strong hydrogen bond acids and strong hydrogen bond bases, except for the tert-butyl iodide transition state in aprotic solvents, which has a rather low hydrogen bond acidity. Thus, the transition states are stabilized by solvents that are hydrogen bond bases (nucleophiles) and are hydrogen bond acids (electrophiles). We show also that the partition of the transition states between water and solvents is aided by both nucleophilic and electrophilic solvents and conclude that the rate of solvolysis of the three halides is increased by both nucleophilic and electrophilic solvents.