Nature Of Nucleophile Research Articles

Preparation and properties of 2-methyl-4-tosyl-1,3-thiazole-5-sulfonyl chloride

Chlorination of readily available 2-methyl-5-methylsulfanyl-4-tosyl-1,3-thiazole has afforded 2-methyl-4-tosyl-1,3-thiazole-5-sulfonyl chloride. The latter can react with amines to build sulfonamides, efficient electrophilic reagents capable of undergoing nucleophilic substitution reactions. Regiochemistry of the described reactions depends strongly on the nature of nucleophiles, used for regioselective synthesis of some previously unknown trisubstituted 1,3-thiazoles.

A turn-on green fluorescent thiol probe based on the 1,2-addition reaction and its application for bioimaging

The nucleophilic nature of thiols is used to develop a novel, sensitive, and highly effective sensor. In this work, we developed a new fluorescent probe for thiols based on fluorescein and maleic anhydride. Among the tested amino acid, only GSH, Cys, Hcy, could turn on the fluorescence emission suggesting that the system was a highly selective sensor for thiols. As a typical biological thiol, GSH was used for further examining the fluorescence response of probe. It is found that probe can detect GSH quantitatively with a detection limit as low as 0.026μM in aqueous/DMSO solution. Moreover its potential for biological applications was confirmed by employing it for fluorescence imaging of thiol in living cells.

Kinetic analysis of mechanochemical chain scission of linear poly(phthalaldehyde).

The kinetics of mechanochemical chain scission of poly(phthalaldehyde) (PPA) are investigated. Ultrasound-induced cavitation is capable of causing chain scission in the PPA backbone that ultimately leads to rapid depolymerization of each resulting polymer fragment when above the polymer's ceiling temperature (Tc ). An interesting feature of the mechanochemical breakdown of PPA is that "half-chain" daughter fragments are not observed, since the depolymerization is rapid following chain scission. These features facilitate the determination of rate constants of activation for multiple molecular weights from a single sonication experiment. Additionally, the degradation kinetics are modified with chain-end trapping agents through variation of the nature and amount of small molecule nucleophile or electrophile.

Reactivities of substituted α-phenyl-N-tert-butyl nitrones.

In this work, a series of α-phenyl-N-tert-butyl nitrones bearing one, two, or three substituents on the tert-butyl group was synthesized. Cyclic voltammetry (CV) was used to investigate their electrochemical properties and showed a more pronounced substituent effect for oxidation than for reduction. Rate constants of superoxide radical (O2•–) reactions with nitrones were determined using a UV–vis stopped-flow method, and phenyl radical (Ph•) trapping rate constants were measured by EPR spectroscopy. The effect of N-tert-butyl substitution on the charge density and electron density localization of the nitronyl carbon as well as on the free energies of nitrone reactivity with O2•– and HO2• were computationally rationalized at the PCM/B3LYP/6-31+G**//B3LYP/6-31G* level of theory. Theoretical and experimental data showed that the rates of the reaction correlate with the nitronyl carbon charge density, suggesting a nucleophilic nature of O2•– and Ph• addition to the nitronyl carbon atom. Finally, the substituent effect was investigated in cell cultures exposed to hydrogen peroxide and a correlation between the cell viability and the oxidation potential of the nitrones was observed. Through a combination of computational methodologies and experimental methods, new insights into the reactivity of free radicals with nitrone derivatives have been proposed.

Divergent Palladium Iodide Catalyzed Multicomponent Carbonylative Approaches to Functionalized Isoindolinone and Isobenzofuranimine Derivatives

2-Alkynylbenzamides underwent different reaction pathways when allowed to react under PdI2-catalyzed oxidative carbonylation conditions, depending on the nature of the external nucleophile and reaction conditions. Thus, oxidative carbonylation of 2-ethynylbenzamides, bearing a terminal triple bond, carried out in the presence of a secondary amine as external nucleophile, selectively led to the formation of 3-[(dialkylcarbamoyl)methylene]isoindolin-1-ones through the intermediate formation of the corresponding 2-ynamide derivatives followed by intramolecular nucleophilic attack by the nitrogen of the benzamide moiety on the conjugated triple bond. On the other hand, 3-[(alkoxycarbonyl)methylene]isobenzofuran-1(3H)imines were selectively obtained when the oxidative carbonylation of 2-alkynylbenzamides, bearing a terminal or an internal triple bond, was carried out in the presence of an alcohol R'OH (such as methanol or ethanol) as the external nucleophile and HC(OR')3 as a dehydrating agent, necessary to avoid substrate hydrolysis. In this latter case, the reaction pathway leading to the isobenzofuranimine corresponded to the 5-exo-dig intramolecular nucleophilic attack of the oxygen of the benzamide moiety on the triple bond coordinated to the metal center followed by alkoxycarbonylation. The structures of representative products have been confirmed by X-ray crystallographic analysis.

Nucleophilic sulfanylation of 1,5-disubstituted pent-2-en-4-yn-1-ones

Regioselectivity of nucleophilic addition of benzenethiols and phenylmethanethiol to 1,5-diarylpent-2-en-4-yn-1-ones in ethanol in the presence of triethylamine at 0–30°C is determined by the nucleophile nature. Phenylmethanethiol adds to the double bond, whereas benzenethiols add to the triple bond. The addition products, 1,5-diaryl-3-benzylsulfanylpent-4-yn-1-ones and 1,5-diaryl-5-(4-arylsulfanyl)penta-2,4-dien-1-ones, respectively, were isolated in 43–89% yield. Substituents in the aryl rings of the substrates did not affect the reaction direction.

Regioselectivity in the Nucleophile Trapping of Arynes: The Electronic and Steric Effects of Nucleophiles and Substituents

The regioselectivity in nucleophile trapping is investigated with arynes generated directly from bis-1,3-diynes. The regioselectivity is profoundly influenced by not only the nature of nucleophiles but also the substituents on the arynes, which is the consequence of both the unfavorable steric interaction between the incoming nucleophile and the nearby substituent and the inherent electronic bias induced by different substituents on the arynes.

ChemInform Abstract: Nanocrystalline and Reusable ZnO Catalyst for the Assembly of Densely Functionalized 4H‐Chromenes in Aqueous Medium via One‐Pot Three Component Reactions: A Greener “NOSE” Approach.

An ecofriendly, one-pot, three component ZnO nanoparticles-mediated synthesis of 4H-chromene in water under thermal condition has been described. The highly product-selective three component electrophilic reaction of 2-hydroxybenzaldehyde with an active methylene compound and another carbon-based varied nature of nucleophile has been developed by a reversible alkylation procedure using greener “NOSE” approach. Greenness of the process was well instituted, as water was used both as reaction media as well as medium for the synthesis of catalyst. In these reactions, the use of nano-ZnO as a catalyst was documented to be crucial for rendering the reactions possible in water media, while replacing nano-ZnO with other acids or bases resulted in the generation of too many side products. The catalyst can be efficiently recycled up to the sixth run, an essential point in the area of green chemistry. The methodology provides cleaner conversion, shorter reaction times, and high selectivity, which make the protocol g...

Synthesis and Bonding in Carbene Complexes of an Unsymmetrical Dilithio Methandiide: A Combined Experimental and Theoretical Study

Herein, we report the preparation of a new unsymmetrical, bis(thiophosphinoyl)-substituted dilithio methandiide and its application for the synthesis of zirconium- and palladium-carbene complexes. These complexes were found to exhibit remarkably shielded (13)C NMR shifts, which are much more highfield-shifted than those of "normal" carbene complexes. DFT calculations were performed to determine the origin of these observations and to distinguish the electronic structure of these and related carbene complexes compared with the classical Fischer and Schrock-type complexes. Various methods show that these systems are best described as highly polarized Schrock-type complexes, in which the metal-carbon bond possesses more electrostatic contributions than in the prototype Schrock systems, or even as "masked" methandiides. As such, geminal dianions represent a kind of "extreme" Schrock-type ligands favoring the ionic resonance structure M(+)-CR2(-) as often used in textbooks to explain the nucleophilic nature of Schrock complexes.

Effect of chemical reactivity of polysulfide toward carbonate-based electrolyte on the electrochemical performance of Li–S batteries

A chemical stability between polysulfides and electrolyte is considered to be crucial to achieving good electrochemical performance of lithium–sulfur (Li–S) batteries since long-chain polysulfides which dissolve easily into common electrolyte can trigger substantial electrolyte decomposition due to their nucleophilic nature. In this work, we investigated the chemical reactivity of polysulfides toward carbonate-based electrolytes through a simple probing experimental method and found that the polysulfides react with carbonate-based electrolytes via a nucleophilic addition or substitution reaction leading to a sudden capacity fading of lithium sulfur cells by loss of active sulfur. This study strongly suggests that electrolytes for Li–S system should not possess an electrophilic functionality to avoid undesired chemical reaction with polysulfides. In addition, we show that the methodology developed in this work for the verification of chemical stability between polysulfides and electrolyte can be widely applicable to screening other potential electrolyte candidates.

Nanocrystalline and Reusable ZnO Catalyst for the Assembly of Densely Functionalized 4H-Chromenes in Aqueous Medium via One-Pot Three Component Reactions: A Greener “NOSE” Approach

An ecofriendly, one-pot, three component ZnO nanoparticles-mediated synthesis of 4H-chromene in water under thermal condition has been described. The highly product-selective three component electrophilic reaction of 2-hydroxybenzaldehyde with an active methylene compound and another carbon-based varied nature of nucleophile has been developed by a reversible alkylation procedure using greener "NOSE" approach. Greenness of the process was well instituted, as water was used both as reaction media as well as medium for the synthesis of catalyst. In these reactions, the use of nano-ZnO as a catalyst was documented to be crucial for rendering the reactions possible in water media, while replacing nano-ZnO with other acids or bases resulted in the generation of too many side products. The catalyst can be efficiently recycled up to the sixth run, an essential point in the area of green chemistry. The methodology provides cleaner conversion, shorter reaction times, and high selectivity, which make the protocol globally putative. The crystal structures of 4H-chromene, easily produced by a chromatography-free highly product-selective reaction, were explored by means of single crystal X-ray diffraction analysis, and H-bonding arrangements of one signified compound prepared is presented. In optimized mild conditions, the isolated yields are 86-93%.

Condensation of phenols and alcohols with 1,2-dichloroethyl-gem-dichlorocyclopropanes

Dichlorocarbenation of 3,4-dichlorobut-1-ene by Makosza method results in the stereoisomeric 1,2-dichloroethyl-gem-dichlorocyclopropanes in a 1:1 ratio. The reaction of the mixture of stereoisomeric gem-dichlorocyclopropanes with phenols and alcohols in dimethylsulfoxide in the presence of solid sodium hydroxide gives rise to the corresponding ketals containing the exocyclic double and triple bonds. In this case, the acetylene compounds dominate in the reaction products. The ratio of the reaction products containing the double and triple bonds depends on the nucleophile nature.

Synthesis and Reactivity of the Unsaturated Trinuclear Phosphanido Complex [(C6F5)2Pt(μ-PPh2)2Pt(μ-PPh2)2Pt(PPh3)

The reaction of [NBu(4)][(C(6)F(5))(2)Pt(μ-PPh(2))(2)Pt(μ-PPh(2))(2)Pt(O,O-acac)] (48 VEC) with [HPPh(3)][ClO(4)] gives the 46 VEC unsaturated [(C(6)F(5))(2)Pt(1)(μ-PPh(2))(2)Pt(2)(μ-PPh(2))(2)Pt(3)(PPh(3))](Pt(2)-Pt(3)) (1), a trinuclear compound endowed with a Pt-Pt bond. This compound displays amphiphilic behavior and reacts easily with nucleophiles L, yielding the saturated complexes [(C(6)F(5))(2)Pt(II)(μ-PPh(2))(2)Pt(II)(μ-PPh(2))(2)Pt(II)(PPh(3))L] [L = PPh(3) (2), py (3)]. The reaction with the electrophile [Ag(OClO(3))PPh(3)] affords the adduct 1·AgPPh(3), which evolves, even at low temperature, to a mixture in which [(C(6)F(5))(2)Pt(III)(μ-PPh(2))(2)Pt(III)(μ-PPh(2))(2)Pt(II)(PPh(3))(2)](2+)(Pt(III)-Pt(III)) and 2 (plus silver metal) are present. The nucleophilic nature of 1 is also demonstrated through its reaction with cis-[Pt(C(6)F(5))(2)(THF)(2)], which results in the formation of [Pt(4)(μ-PPh(2))(4)(C(6)F(5))(4)(PPh(3))] (4). The structure and NMR features indicate that 1 can be better considered as a Pt(II)-Pt(III)-Pt(I) complex instead of a Pt(II)-Pt(II)-Pt(II) derivative. Theoretical calculations (density functional theory) on similar model compounds are in agreement with the assigned oxidation states of the metal centers. The strong intermetallic interactions resulting in a Pt(2)-Pt(3) metal-metal bond and the respective bonding mechanism were verified by employing a multitude of computational techniques (natural bond order analysis, the Laplacian of the electron density, and localized orbital locator profiles).

Studies on the ring-opening of bicyclic cyclopropanes activated by a carbonyl group

Studies on the Friedel–Crafts reaction between carbonyl bicyclic cyclopropane and electronic-rich aromatic systems were conducted. Lewis acid and iminium cationic activation methods were examined. It was found that the cyclopropane ring-opening was highly dependent on the nature of the counter nucleophile as well as the activation method.

Physicochemical characterization of cationic gemini surfactants and their effect on reaction kinetics in ethylene glycol–water medium

Micellar and surface properties of two cationic gemini surfactants viz. alkanediyl-α,ω-bis(hydroxyethylmethylhexadecylammonium bromide) (C16-s-C16, MEA 2Br−, where s=4, 6) in aqueous and ethylene glycol–water medium (0–20%, v/v) have been investigated by conductivity and surface tension measurements. The values of critical micellar concentration (CMC) and degree of micellar ionization (α) increase by increasing the concentration of ethylene glycol and the spacer chain length of gemini surfactants. The standard Gibbs free energy changes (ΔGm°), enthalpies (ΔHm°) and entropies (ΔSm°) of micellization of gemini surfactants, determined by studying the variation of critical micelle concentration with temperature, revealed spontaneous and exothermic micellization behavior. The large rate enhancement for the hydrolysis of p-nitrophenyl acetate (PNPA) and p-nitrophenyl diphenyl phosphate (PNPDPP) by α-nucleophiles such as, benzohydroxamic acid (BHA), acetohydroxamic acid (AHA), salicylhydroxamic acid (SHA) and butane-2,3,-dione monooxime (BDMO) were obtained in the presence of gemini surfactants over the monomeric surfactant i.e. cetyltrimethylammonium bromide (CTAB). Kinetic constants were observed to be dependent on spacer chain length of gemini surfactants as well as on the nature of nucleophiles used. Ethylene glycol retarded the rate of reaction and C16-6-C16, MEA 2Br− showed better catalytic effect for phosphate ester hydrolysis.

ChemInform Abstract: Amidines, Isothioureas, and Guanidines as Nucleophilic Catalysts

AbstractReview: 66 refs.

A New Application Area for Ag‐NHCs: CO2 Fixation Catalyst

AbstractThe first example of the silver‐NHC catalyzed cycloaddition of CO2 to terminal epoxides is reported. The choice of NHC substituents, halides and the nature of additives were determined to be important. Ionic [(Cnmim)2Ag]2[Ag2Br4] (Cnmim=1‐(CnH2n+1)‐3‐methylimidazol‐2‐ylidene; n=4–18) catalysts exhibited a high yield of styrene carbonate (77–92 %) in the presence of 4‐dimethylaminopyridine (DMAP) as a cocatalyst without needing any solvent. The catalytic activity improved as the length of the alkyl groups (n) increased, although substituents longer than C14 did not produce any further beneficial effect. For the protocol performed at 1.5 MPa pressure and 100 °C the TOF was calculated to be 440 h−1. A prolonged reaction time and increased pressure of CO2 increased the yield. Used without any additive, compound C14 was able to fix CO2 with PO (propylene oxide) quantitatively at 120 °C, 2.0 MPa and could be used at least seven times without loss of activity and selectivity. The nucleophilic nature of the anion is decisive for the formation of the product.

Endocannabinoid Enzyme Engineering: Soluble Human Thio-Monoacylglycerol Lipase (sol-S-hMGL)

In the mammalian central nervous system, monoacylglycerol lipase (MGL) is principally responsible for inactivating the endocannabinoid signaling lipid 2-arachidonoylglycerol (2-AG) and modulates cannabinoid-1 receptor (CB1R) desensitization and signal intensity. MGL is also a drug target for diseases in which CB1R stimulation may be therapeutic. To inform the design of human MGL (hMGL) inhibitors, we have engineered a Leu(Leu(169);Leu(176))-to-Ser(Ser(169);Ser(176)) double hMGL mutant (sol-hMGL) which exhibited enhanced solubility properties, and we further mutated this variant by substituting its catalytic-triad Ser(122) with Cys (sol-S-hMGL). The hMGL variants hydrolyzed both 2-AG and a fluorogenic reporter substrate with comparable affinities. Our results suggest that the hMGL cysteine mutant maintains the same overall architecture as wild-type hMGL. The results also underscore the superior nucleophilic nature of the reactive catalytic Ser(122) residue as compared to that of Cys(122) in the sol-S-hMGL mutant and suggest that the nucleophilic character of the Cys(122) residue is not commensurately enhanced within the three dimensional architecture of hMGL. The interaction of the sol-hMGL variants with the irreversible inhibitors AM6580 and N-arachidonylmaleimide (NAM) and the reversible inhibitor AM10212 was profiled. LC/MS analysis of tryptic digests from sol-S-hMGL directly demonstrate covalent modification of this variant by NAM and AM6580, consistent with enzyme thiol alkylation and carbamoylation, respectively. These data provide insight into hMGL catalysis, the key role of the nucleophilic character of Ser(122), and the mechanisms underlying hMGL inhibition by different classes of small molecules.

High pressure promoted aza-Michael addition of primary and secondary amines to α-substituted acrylates

The α-dialkoxymethyl α,β-unsaturated ester 1 can be easily converted, under high pressure and at ambient temperature, into the corresponding aza-Michael adducts 2 and/or push–pull α-aminomethyl-β-methoxy-α,β-unsaturated esters 3 by treatment with primary or secondary amines. The ratio between these two types of products is shown to depend on the nature of the nitrogen nucleophile.

Amidines, isothioureas, and guanidines as nucleophilic catalysts

Over the last ten years there has been a huge increase in development and applications of organocatalysis in which the catalyst acts as a nucleophile. Amidines and guanidines are often only thought of as strong organic bases however, a number of small molecules containing basic functional groups have been shown to act as efficient nucleophilic catalysts. This tutorial review highlights the use of amidine, guanidine, and related isothiourea catalysts in organic synthesis, as well as the evidence for the nucleophilic nature of these catalysts. The most common application of these catalysts to date has been in acyl transfer reactions, although the application of these catalysts towards other reactions is an increasing area of interest. In this respect, amidine and guanidine derived catalysts have been shown to be effective in catalysing aldol reactions, Morita-Baylis-Hillman reactions, conjugate additions, carbonylations, methylations, silylations, and brominations.