Ion-pair Mechanism Research Articles

Phase-Transfer Nucleophilic Reactions Using Water-Insoluble Alcohols as Organic Solvents

Abstract Simple nucleophilic substitutions were done under liquid–liquid phase-transfer reaction conditions using water-insoluble alcohols as organic solvents. The reactions proceeded at considerable rates even in the absence of any catalysts, depending on the alcohol, inorganic salt, and the aqueous concentration of the salts. An addition of single- or double-chained onium salts enhanced the reaction rate almost linearly with the amount of the onium salts. The concentrations of inorgainc salts and water in the alcohol phase were analyzed and the relationship between these concentrations and the observed rate constant was discussed. An interfacial reaction mechanism explains the kinetics of this reaction system better than the conventional ion-pair mechanism assumed by most research using hydrocarbon solvents.

Dehydrobromination of 1,1-diaryl-1,2-dibromoalkanes catalyzed by iron and iron bromides. An ion-pair-mediated reaction?

The participation of ion-paired Lewis acid/Lewis base in the dehydrohalogenations of 1,2-dibromo-1,1 -diarylalkanes catalyzed by Fe0 and by Fe(II) and Fe(III) bromides was investigated. The reactivities of the catalyst employed were correlated with their chemical hardness. The influence of para substituents on the phenyl rings of the substrates and the results obtained in Lewis-acid-catalyzed and thermal dehydrobromination of the same compounds were compared. The experimental results could not be explained in terms of a Lewis-acid-catalyzed dehydrobromination. Keywords: dehydrohalogenation, bromoalkanes, Lewis acid catalysts, ion-pair mechanism.

The acidity scale of HCl solutions in N,N-dimethylformamide

The scale of the thermodynamic acidity of HCl solutions in DMF has been measured at 25 and 39.5 °C up to 15 mol L−1 acid concentration by the indicator method. It is shown that in the HCl-DMF system the ionization of the nitroaniline-derived indicators occurs by the ion pair mechanism. Within the temperature range studied acidity is independent of temperature. Indicators of the nitroaniline series are used.

Fluorinated pyrimidines. Part 4. Synthesis, properties and stereochemical conversion of the cis and trans isomers of 6-alkoxy-5-fluoro-5,6-dihydrouracils

The reaction of 6-acetoxy-5-fluoro-5,6-dihydrouracil with ROH (R = Me, Et, Pr, Pri, Bu, But) under acidic conditions has been investigated using 18F as a tracer. The quantitative replacement of the OAC-group proceeded predominantly with cisoid(gauche) stereochemistry, but upon prolonged heating the amount of the trans compound increased. This isomerization did not originate from epimerization at C5. The trans compounds—apart from being more stable towards substitution and elimination than the corresponding cis compounds—gave invariably substitution products with inversion of configuration, while the cis compounds mainly retained their configuration. Within the concept of the unifying ion-pair mechanism it is proposed that the trans compound reacts via an intimate protonated intermediate and the cis compound via a solvent-separated protonated intermediate. As a result, it was not the gauche attraction between the fluorine atom and the incoming nucleophile, but the poor π-donor ability of the C–F bond that was the determining factor in the cisoid stereochemistry of 5-fluoro-5,6-dihydrouracil adducts.

Counterion effects in intramolecular charge transfer in radical anions

The influence of the presence of an electrolyte in a low-polarity solvent (tetrahydrofuran) on the rate of a weakly exoergic ([approx]50 meV) nonadiabatic intramolecular charge shift reaction and on the position of the charge transfer absorption band in a degenerate system has been studied by pulse radiolysis. The investigation focused in particular on the dependence of the effect on the size of the cation of the chemically inert electrolyte. Electrolytes caused dramatic rate reductions of 2-3 orders of magnitude. Unexpectedly, the rate reduction was found to increase with an increasing size of the cation. The recorded spectral blue shifts were as large as 0.5 eV and exhibited the expected tendency; the smaller counterions produced larger spectral shifts, due to a stronger Coulombic interaction. In both cases the effects exceeded the limits predicted by the continuum approach and pointed to the ion-pairing mechanism. The discrepancy between the dependence of the thermal electron transfer and the optically assisted electron transfer on the radius of the counterion could not be easily explained on purely energetic grounds, and the dynamics of the counterion had to be considered. Unfortunately, no agreement between the experimental results and the Eigen model of dissociative diffusion of ion pairsmore » in the zero ionic strength limit could be found. However, a qualitative correlation between the measured rates and the dissociation constants of the used salts, as well as the counterion mobilities was observed. 34 refs., 8 figs., 3 tabs.« less

Mass Measurements of Ferrocene Adsorption at Gold Films with the Electrochemical Quartz Crystal Microbalance

We present evidence of ferrocene adsorption from acetonitrile onto gold thin films with the electrochemical quartz crystal microbalance. The adsorption occurs upon oxidation and the limit of deposition is equivalent to ca. ten monolayers of ferrocene. An increase in adsorption is also observed when the concentration of water in the acetonitrile solution is increased. An ion pairing mechanism followed by the precipitation of ferrocenium perchlorate is proposed.

The Extraction of Nickel with Aliphatic Oximes

Abstract U.S. Bureau of Mines researchers investigated the use of aliphatic oximes to extract nickel from acidic, nickelous-chromic-chloride solutions. Batch solvent extraction tests were conducted to characterize the nickel extraction and stripping properties of several oximes. Results indicated that the oximes selectively extracted nickel over chromium by an ion pair mechanism. Nickel was most effectively stripped from the loaded oxime extractants with dilute hydrochloric acid; however, these acidic strip solutions partially degraded the oximes to their parent aldehydes by hydrolysis. The oximes could, however, be regenerated by contacting the solvent phase with a neutralized hydroxylamine-hydrochloride solution. Decyl oxime was successfully used in a continuous counter-current solvent extraction circuit that incorporated loading, stripping, and regeneration stages. The decyl oxime degraded 12 pct per loading and stripping cycle, but was effectively regenerated prior to recycling to the head of the circuit.

Anchimeric assistance of the CO2CH3substituent in the elimination kinetics of 3-(methoxycarbonyl)propyl methanesulfonate in the gas phase

The elimination kinetics of 3-(methoxycarbonyl)propyl methanesulfonate have been determined in a static system over the temperature range of 289.3–329.8 °C and pressure range of 43–111 torr. The reaction, in vessels seasoned with allyl bromide and in the presence of at least an equal amount of the free radical suppressor toluene, is homogeneous, unimolecular and first-order kinetically. The rate coefficients follow the Arrhenius equation: log k1=(13.50 ± 0.47)–(182.2 ± 5.3)(2.303 RT)–1. A very high extent of lactone formation suggests an unequivocal participation of the carbonyl oxygen of the CO2CH3 group. The partial rates for the parallel elimination towards the formation of butyrolactone and a small amount of methylbut-3-enoate have been estimated, reported, and discussed. The present results provide further evidence of intimate ion pair mechanisms in the gas phase pyrolyses of special types of organic molecules.

The ion-pair mechanism in square planar substitution. Displacement of dimethyl sulfoxide from chloro(dimethyl sulfoxide)(N,N,N'N'-tetramethyldiaminoethane)platinum(II) salts by halide ions in dichloromethane solution

Freshly prepared [Pt(Me 4 en)(Me 2 SO)Cl]Cl rapidly loses Me 2 SO in the solid state to give [Pt(Me 4 en)Cl 2 ]. This reaction also occurs in chloroform and dichloromethane solution. The Kinetics are first-order with a rate constant that is independent of the initial concentration of the complex and of added [Me 2 SO].

Is gauche attraction between the fluoro atom and the incoming nucleophile really the determining factor in cissoid stereochemistry?

Recently we described the unexpected concomitant formation of the ‘antigauche’ trans isomer during the synthesis of 5-fluoro-6-alkoxyuracils ( J. {Fluorine Chem., 54} (1991) 190). With respect to their conformation, in both the cis and the trans compounds, the anomeric effect (substituent at C 6 axial to N 1) appeared to be the predominant factor (see diagram). ▪ R = Me, Et, n−Pr, i−Pr, n−Bu, t−Bu. Both 5-F-6-OR isomers were found to undergo substitution reactions at C 6 under acidic conditions. By carrying out these substitution reactions (with variation of the group R) in different alcohols (R′OH) or alcohol mixtures (R′OH + R″OH) at different temperatures and in the presence or absence of CH 3CN, we found that in all cases the trans compound was more stable against substitution than its corresponding cis compound. Also their substitution pattern differed invariably: the trans compounds gave exclusively S N2 substitution products, the cis compounds (mainly) S N1 products. Within the concept of the unifying ion-pair mechanism it will be suggested that, because in the trans compound the fluoro atom destabilizes the formation of a developing carbocation, the trans compound is ‘blocked’ in the intimate protonated intermediate state while the cis compound, having the fluoro atom orthogonal to the developing empty π-orbital, reacts through a solvent separated intermediate and partly through a dissociated intermediate. Consequently, a refinement of the nature of the cissoid sreochemically will be proposed.

Studies of formal [1,5]-sigmatropic thermal rearrangements of dimethyl 3-alkyl-3-methyl-3H-pyrazole-4,5-dicarboxylates and dimethyl 4-alkyl-5-methyl-4H-pyrazole-3,4-dicarboxylates

Studies of the thermal rearrangements of 3H-pyrazoles, 10a-e, in benzene/toluene, chloroform, and methanol solvents are described. The mechanism for rearrangement appears to be two-step, involving discrete ion-pair intermediates. Large rate enhancements for these rearrangements in methanol and canion trapping by methanol are consistent with the proposed mechanism. Observed rate constants for the rearrangements of 3H-pyrazoles 10c, 10d, and 10e in benzene-d 6 were determined. Insight into the sense of rearrangement by an ion-pair mechanism is also provided by analysis of the 1 H NMR spectra of the product mixtures

Interaction of immunoglobulin G with immobilized histidine: mechanistic and kinetic aspects

A systematic investigation of coupling methods for and the chemistry and chromatographic parameters of immunoglobulin gamma (IgG) adsorption to bistidine- and imidazole-coupled Sepharose gels was undertaken in order to elucidate the interactions involved in the mechanism of recognition between IgG and the immobilized histidine. The effects of pH, salt and temperature effects indicated an ion-pairing mechanism, rather than a mechanism based on the net charge of the protein (IgG), but with some localized complementary charges recognizing the unprotonated imidazole nitrogen. The effects of the addition of ethylene glycol and urea indicated the involvement of hydrogen bonding between the ligand and the protein. The immobilized histidine binds to the Fc fragment of IgG with a fairly low affinity, in a way similar to the N-terminum of protein A binding to the Fc fragment of IgG. The kinetic parameters of the chromatographic system indicated a good capacity but a low adsorption rate constant.

Retention processes on α 1-acid glycoprotein-bonded stationary phase

Stereoselective separations of charged enantiomers on CHIRAL-AGP can be controlled by varying the pH and adding charged and uncharged additives to the mobile phase. The interaction with the selector, α 1-acid glycoprotein, was studied by monitoring the effects of the variables on retention and by indirect detection, in part using a simple multivariate design. The stereoselectivity is due to simultaneous retention processes involving ion-exchange and ion-pairing mechanisms. The predominant mode of interaction for different solutes was elucidated from variables that promote or counteract either of the processes. Considerable improvements in the stereoselectivity were achieved with chiral or achiral anionic and cationic additives that act in a synergistic or competitive mode.

Sodium-Dependent Retention of Prostaglandins in Rat Ileum

An intestinal perfusion technique is reported to study the steady-state ileal mucosal retention of labeled prostaglandins E1, E2, and F2α in rats. Ileal homogenates were analyzed for [3H]prostaglandin E1, [14C]prostaglandin E2, and [14C]prostaglandin F2α after intestinal segments were perfused with Krebs improved Ringer buffers containing sodium or depleted from sodium and replaced with choline, and buffers containing 1 mM ouabain, 2 mM amiloride, or 50 nM tetrodotoxin. Prostaglandin ileal mucosal uptake was also studied after iv injection of tetrodotoxin (20 μg/kg body weight). Prostaglandin concentration-dependent transport studies support passive uptake mechanisms for prostaglandin E1 and E2. Physiological concentrations of sodium increased labeled prostaglandins E1, E2, and F2α ileal mucosal uptake and decreased n-octanol–buffer partition coefficients. Unlike sodium, potassium showed no effect on labeled prostaglandin ileal transport. Ouabain, amiloride, and tetrodotoxin in the perfusates did not significantly alter prostaglandin mucosal uptake. However, injecting tetrodotoxin into rats caused a drastic increase of prostaglandin uptake through the ileal mucosa. Therefore, the role of sodium on labeled prostaglandin E1, E2, and F2α ileal mucosal transport can be postulated to be controlled by either one or both of the following mechanisms: a pH-partition passive transport mechanism, and/or a sodium channel-dependent pathway whereby prostaglandin permeation possibly proceeds via a sodium-prostaglandin ion-pair mechanism which is controlled by a gating phenomenon.

The pH Influence on the HPLC-Retention of Chemotherapeutic Fluoroquinolone Derivatives

Abstract The gyrase inhibitor fluoroquinolone derivatives were investigated by RP-HPLC methods in C18/methanol-phosphate buffer system. Considering the amphoteric feature of the substances it was reasonable to study the relationship between their chromatographic behaviour vs. pH of the mobil phase. The formation of k1 values was characterized by a maximum curve, and the retention maxima could be found close to or at the pH values of isoelectric point of the compounds. This may be explained by the presence of the zwitter ionic or the unionized form of the derivatives at this pH value. By addition of ion-pairing (IP) agent (cetrimide or hexanesulfonic acid) in different concentration to the eluent a definite k' value increase (formation of a characteristic saturation type curve) was observed indicating an ion-pairing mechanism. In case of IPHPLC significant correlation was found between the octanol-water partition coefficients measured at the isoelectric point or at pH 7. 4, and the retention values of the ...

Bile acid structure-activity relationship: evaluation of bile acid lipophilicity using 1-octanol/water partition coefficient and reverse phase HPLC.

Two independent methods have been developed and compared to determine the lipophilicity of a representative series of naturally occurring bile acids (BA) in relation to their structure. The BA included cholic acid (CA), chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), deoxycholic acid (DCA), hyodeoxycholic acid (HDCA), ursocholic acid (UCA), hyocholic acid (HCA), as well as their glycine and taurine amidates. Lipophilicity was determined using a 1-octanol/water shake-flask procedure and the experiments were performed at different pH and ionic strengths and at initial BA concentrations below their critical micellar concentrations (CMC) and the water solubility of the protonated form. The experimental data show that both the protonated (HA) and ionized (A-) forms of BA can distribute in 1-octanol, and consequently a partition coefficient for HA (logP' HA) and for A- (logP' A-) must be defined. An equation to predict a weighted apparent distribution coefficient (D) value as a function of pH and pKa has been developed and fits well with the experimental data. Differences between logP for protonated and ionized species for unconjugated BA were in the order of 1 log unit, which increased to 2 for glycine-amidate BA. The partition coefficient of the A- form increased with Na+ concentration and total ionic strength, suggesting an ion-pair mechanism for its partition into 1-octanol. Lipophilicity was also assessed using reverse phase chromatography (C-18-HPLC), and a capacity factor (K') for ionized species was determined. Despite a broad correlation with the logP data, some BA behaved differently. The logP values showed that the order of lipophilicity was DCA greater than CDCA greater than UDCA greater than HDCA greater than HCA greater than CA greater than UCA for both the protonated and ionized unconjugated and glycine-amidate BA, while the K' data showed an inversion for some BA, i.e., DCA greater than CDCA greater than CA greater than HCA greater than UDCA greater than HDCA greater than UCA. The logP data fitted well with other indirect measurements of BA monomeric lipophilicity such as albumin binding or accessible total hydrophobic surface area data calculated by energy minimization and molecular computer graphics. Differences between unconjugated and amidated BA are consistent with the presence of an amide bond and a lower pKa when pH dependence was studied. Capacity factors, on the other hand, were related to properties of BA micelles such as cholesterol-solubilizing capacity and membrane disruption, reflecting the BA detergency.(ABSTRACT TRUNCATED AT 400 WORDS)

The mechanism of adsorption of aurocyanide onto activated carbon, 1. Relation between the effects of oxygen and ionic strength

The poor agreement between different workers regarding the exact mechanism involved in the adsorption of aurocyanide onto activated carbon is shown to be due to differences in the experimental conditions they employed. The effects of oxygen and ionic strength are shown to be interrelated. Adsorption under conditions of high ionic strength, as found in gold plants, involves an ion-pair mechanism whereas, under conditions of low ionic strength, a portion of the gold is adsorbed by electrostatic interacyion with ion-exchange sites formed through oxidation of the carbon surface by molecular oxygen.

Physicochemical aspects of the transdermal delivery of Bupranolol

The skin absorption of Bupranolol has been measured in an assessment of the feasibility of delivering this drug transdermally. Basic physicochemical parameters such as partitioning are influenced by the presence of oleic and lauric acids. It is possible to enhance the transfer of Bupranolol across a model isopropyl myristate membrane by an ion pair mechanism involving these two fatty acids. They did not, however, significantly enhance transfer across in vitro human skin. A kinetic model based on physicochemical parameters can predict satisfactorily the transdermal delivery of this β-blocker

ChemInform Abstract: The Mechanism in the Elimination Kinetics of 2‐Chloropropionic Acid in the Gas Phase.

The elimination kinetics of 2-chloropropionic acid have been studied over the temperature range of 320–370.2°C and pressure range of 79–218.5 torr. The reaction in seasoned vessel and in the presence of the free radical suppressor cyclohexene, is homogeneous, unimolecular, and obeys a first-order rate law. The dehydrochlorination products are acetaldehyde and carbon monoxide. The rate coefficient is expressed by the following Arrhenius equation: log k1(s−1) = (12.53 ± 0.43) – (186.9 ± 5.1) kJ mol−1 (2.303RT)−1. The hydrogen atom of the carboxylic COOH appears to assist readily the leaving chloride ion in the transition state, suggesting an intimate ion pair mechanism operating in this reaction.

The mechanism in the elimination kinetics of 2‐chloropropionic acid in the gas phase

AbstractThe elimination kinetics of 2‐chloropropionic acid have been studied over the temperature range of 320–370.2°C and pressure range of 79–218.5 torr. The reaction in seasoned vessel and in the presence of the free radical suppressor cyclohexene, is homogeneous, unimolecular, and obeys a first‐order rate law. The dehydrochlorination products are acetaldehyde and carbon monoxide. The rate coefficient is expressed by the following Arrhenius equation: log k1(s−1) = (12.53 ± 0.43) – (186.9 ± 5.1) kJ mol−1 (2.303RT)−1. The hydrogen atom of the carboxylic COOH appears to assist readily the leaving chloride ion in the transition state, suggesting an intimate ion pair mechanism operating in this reaction.