The basicity of pyridine and its tendency towards cationic homoconjugation in non‐aqueous media

Acid dissociation constant, pK_a, of protonated pyridine, determined in the polar protophobic aprotic solvent, acetone, has been compared with pK_a values of the pyridinium ion in a variety of other polar solvents including aprotic protophobic ones, acetonitrile, benzonitrile, nitrobenzene, nitromethane, and propylene carbonate, in the protophilic aprotic dimethyl sulfoxide and N,N‐dimethylformamide, as well as in the amphiprotic methanol. On the basis of the set of these pK_a values, the effect of the medium on the basicity of pyridine is discussed. Further, based on the cationic homoconjugation constants of pyridine conjugated with the pyridinium cation in the non‐aqueous solvents, the tendency of pyridine towards homoconjugation reactions has also been discussed. Finally, both the basicity of pyridine and its tendency towards cationic homoconjugation has been compared with analogous properties of pyridine N‐oxide.     

Basicity comparison for di-substituted 4-nitropyridine derivatives in polar non-aqueous media

Acid dissociation, as well as cationic homoconjugation equilibria have been studied potentiometrically in systems involving four di-substituted 4-nitropyridines and conjugate cationic acids in the polar non-aqueous solvents - aprotic protophobic acetonitrile (AN) and propylene carbonate (PC), the amphiprotic methanol (MeOH), and in the aprotic protophilic dimethyl sulfoxide (DMSO). The influence of solvent effect on the obtained acidity constants has been discussed. The acidity constants (expressed as pK_a values) were compared with those previously determined in another polar protophobic aprotic solvent - acetone (AC), and obtained for the unsubstituted pyridine (Py). A comparison of the acid dissociation constants determined in all media studied has proved that the strength of the cationic acids increases on going from acetonitrile through propylene carbonate, acetone, and methanol to dimethyl sulfoxide. Furthermore, the values of acidity constants in the non-aqueous media have shown that in all the solvents studied they change according to the substituent effects. It has been also found that substituted 4-nitropyridine derivatives studied exhibit no tendency towards cationic homoconjugation in acetonitrile, propylene carbonate, and methanol and dimethyl sulfoxide. Moreover, it has been demonstrated that the acid dissociation constants determined by potentiometric titration method in all the solutions investigated correlate well with the calculated energy parameters of the protonation reactions in the gaseous phase.     

Capillary zone electrophoresis of basic drugs in non-aqueous acetonitrile with buffers based on a conventional pH scale

Summary The pK _a ^* values of 10 nitrogen-containing basic drugs in non-aqueous acetonitrile were determined from the pH^* dependence of their electrophoretic mobilities. The pH^* scale in the organic solvent was established using background electrolytes with known conventional pK _a ^* values, making further calibration with reference pH electrodes unnecessary. In acetonitrile the pK _a ^* values of analytes (or their conjugated cation acids, BH⁺, respectively) were 5.2±8.9 pK units>those in water. The observed change in pK _a ^* values of cationic analytes was, however, much less than the known respective change for neutral acids type HA. From the pK _a ^* values and the actual mobilities, it is possible to predict pH^* conditions to enable separation of analytes, and this was demonstrated for two pairs of common drugs.     

Acidity of Several Anilinium Derivatives in Pure Tetrahydrofuran

The acidity constant (pK _a) of eleven substituted anilinium ions and the dissociation constants of their perchlorate salts (pK _salt) were determined in pure tetrahydrofuran by potentiometry and conductometry. The pK _a values of the studied aniliniums extend downward the range of previously determined pK _a values. The resolution of acid strength for cationic acids in tetrahydrofuran was compared with those obtained in other amphiprotic and aprotic solvents. It is shown that the resolution in tetrahydrofuran is higher than the ones in water and methanol, similar to those in acetone, dimethyl sulfoxide and isobutylmethylketone, but lower than those in acetonitrile and nitromethane.     

Studies on acid–base equilibria of 4-R-2,6-dimethylpyridine N-oxide systems in non-aqueous solvents

Acid–base equilibrium constants, i.e. acid dissociation, cationic homoconjugation and cationic heteroconjugation constants in 4-R-2,6-dimethylpyridine N-oxide systems (where R denotes methoxy-, methyl-, chloro- or nitro-group) in polar non-aqueous solvents: protophobic aprotic nitromethane, acetonitrile and acetone, protophilic aprotic N,N-dimethylformamide and amphiprotic methanol have been determined. The acidity constant values of protonated N-oxides in solvents studied have been found to change according to the substituent effect and to the sequence of acidity changes in water. This finding allowed to correlate the pK_a values determined in water with those determined in the solvents studied. Further, it was found that the cationic homo- and heteroconjugation constant values increased with decreasing solvent basicity and with increasing basicity of the N-oxide, and in the case of heteroconjugating systems, with increasing basicity of the the proton acceptor.     

A potentiometric study of acid–base properties of the (phenol + phenolate) systems in acetonitrile and, (acetonitrile + cyclohexane) solvent system

Acid–base equilibria were studied potentiometrically in (phenol + phenolate) systems involving nine substituted phenols with both electron-donating and electron-accepting substituents in a polar protophobic aprotic solvent, acetonitrile. To estimate the influence of the polarity of the medium on acid dissociation and anionic homoconjugation equilibria, the equilibrium constants were also determined in an (acetonitrile + cyclohexane) solvent in which the latter was a diluent that lowered the dielectric permittivity of the reaction medium, and compared with those determined in acetonitrile.     

The cation binding of benzo crown ethers in acetonitrile using fluorescence spectroscopy

The effects of Na⁺, K⁺ and Li⁺ cations on the fluorescence spectra of benzo[15]crown-5, benzo[18]crown-6 and dibenzo[18]crown-6 were investigated in acetonitrile. The alkali cation role observed was usually the complexation-enhanced quenching fluorescence effect (CEQF) in acetonitrile due to the increased fluorescence quenching rate of the complexed fluoroionophore. The association constants for 1 :1 stoichiometry InK _a have been obtained using the relationship 1/K _a[L ₀] = (1 –P)²/P. It was shown that the preferential interaction rule of compatibility of cationic radii and macrocyclic ring size is in excellent agreement with the association constants obtained by fluorescence spectroscopy. The order of InK _a found for benzo[15]crown-5 complexation was Li⁺ > Na⁺ > K⁺ and K⁺ > Na⁺ > Li⁺ for benzo[18]crown-6 in acetonitrile.Presented at the Sixth International Seminar on Inclusion Compounds, Istanbul, Turkey, 27–31 August, 1995.     

Acid-base equilibria of substituted pyridine N-oxides in methanol

Acid dissociation constants in methanol for eight substituted pyridine N-oxides having a wide range of acid-base properties, [quinoline N-oxide (bi-cyclic amine N-oxide) and pyridine (heterocyclic amine)] have been determined using the potentiometric titration method. A linear correlation between ourmethanol data and aqueous pK _a values from the literature has been found. As in polar aprotic solvents cationic homoconjugation phenomenon has been found to be present for sufficiently basic N-oxides. The tendency of substituted pyridine N-oxides towards cationic homoconjugation in methanol is weaker than in polar aprotic solvents and increases with increasing basicity of N-oxides. It has also been found that, in contrast to polar aprotic solvents, the cationic homoconjugation phenomenon in methanol is much more pronounced for heterocyclic amines than their N-oxides.     

Ratiometric Near-Infrared Fluorescent Probes Based on Hemicyanine Dyes Bearing Dithioacetal and Formal Residues for pH Detection in Mitochondria

Ratiometric near-infrared fluorescent probes (AH⁺ and BH⁺) have been prepared for pH determination in mitochondria by attaching dithioacetal and formal residues onto a hemicyanine dye. The reactive formyl group on probe BH⁺ allows for retention inside mitochondria as it can react with a protein primary amine residue to form an imine under slightly basic pH 8.0. Probes AH⁺ and BH⁺ display ratiometric fluorescent responses to pH changes through the protonation and deprotonaton of a hydroxy group in hemicyanine dyes with experimentally determined pKa values of 6.85 and 6.49, respectively. Calculated pK_a values from a variety of theoretical methods indicated that the SMD_BONDI method of accounting for solvent and van der Waals radii plus including a water molecule located near the site of protonation produced the closest overall agreement with the experimental values at 7.33 and 6.14 for AH⁺ and BH⁺ respectively.     

Relation between stability constants of metal ion cryptates in two solvents and the transfer activity coefficients of the metal ions

The extrathermodynamic assumption of Lejaille and Bessière that _1,2 log K (LM ⁿ⁺ )=–G _tr (M ⁿ⁺ ) in which K is stability constant and L is cryptand 2.2.2, 2 _B 2 _B 2, 2.2.1, or 2.1.1 has been tested in dipolar aprotic solvents for M ⁿ⁺ being Li⁺, Na⁺, K⁺, Ag⁺, Tl⁺, and Ba²⁺. The relation has been found generally acceptable for the dipolar aprotic solvents propylene carbonate, acetonitrile, N,N-dimethylformamide and dimethylsulfoxide, provided the size of the ion is equal to or smaller than the cavity of the cryptand. The relation does not hold for the hydrogen bonded donating solvents, water, and methanol.     

Cationic Heteroconjugation Constants in the OHN+ and NHO+ Systems in Propylene Carbonate: Dependence on Difference in Basicity

Cationic heteroconjugation equilibria of more than ninety systems consisting of substituted pyridines, their N-oxides, and trimethylamine N-oxide, i. e., in systems with mixed hydrogen bridges of type OHN⁺ (NHO⁺) were studied in propylene carbonate. Both experimental systems without proton transfer, BH⁺/B₁, and those with proton transfer, B₁H⁺/B, were explored. The stability of the mixed hydrogen bridges, OHN⁺ (NHO⁺), is compared with that of the OHC⁺-type bridges. The influence of the difference in basicity of the conjugate base of the proton donor and the proton acceptor on the presence of the proton transfer equilibria, and, consequently, the possibility of determination of the cationic heteroconjugation constant values is discussed.     

Solvent Effect on Deprotonation Equilibria of Acids of Various Charge Types in Non-aqueous Isodielectric Mixtures of Protic Ethylene Glycol and Dipolar Aprotic N,N-Dimethylformamide at 298.15 K

Deprotonation constants of phthalic (H₂A) and biphthalic (HA⁻) acids and of mono-protonated (BH⁺) and di-protonated (BH₂²⁺) piperazine acids have been determined at 25 °C by measuring the Emf of galvanic cells comprising H⁺-sensitive glass GE(H⁺) and Ag,AgCl electrodes in non-aqueous isodielectric mixtures of protic ethylene glycol (EG) and dipolar aprotic N,N-dimethylformamide (DMF). Solvent effects on deprotonation of the acids: ∂(ΔG _diss^o)=2.303RT[p(_s K _a)−p(_R K _a)], have been dissected into transfer Gibbs energies, ΔG _t^o _, of the species involved by evaluating ΔG _t^o of the uncharged phthalic acid and base piperazine (B) from the measured solubilities of the acid and base, respectively, and using ΔG _t^o of H⁺ based on the TATB reference electrolyte assumptions, as evaluated earlier. The contributions of the different species involved in the protolytic equilibria i.e., H⁺,H₂A,HA⁻,BH₂²⁺ and BH⁺ and their respective conjugate bases HA⁻,A²⁻,BH⁺ and B have been discussed in terms of their solvation behavior as guided by the ‘acid-base’, dispersion, structural and electronic characteristics of the acid-base species and of the co-solvent molecules and binary mixtures, ignoring the Born-type electrostatic interactions on the ionic species as the solvent system is quasi isodielectric.     

Basicity of some aliphatic amines in mixed H2O?CH3CN solvents

The values of pK_a^ms (K_a^ms represents ionization constant of conjugate acid of amine base in mixed water–acetonitrile solvent) for all amines, except for charged amine bases, show a mild decrease (ca. 0.1–0.4 pK units) with the increase in CH₃CN content from 2 to ∼60% v/v. However, the pK_a^ms values at 70% v/v CH₃CN become nearly equal or slightly larger (by ≤0.7 pK units) than the corresponding pK_a^ms at 2% v/v CH₃CN for all neutral and charged amines. The values of pK_a^ms for phenol increase from 10.17 to 13.38 with the increase in the content of CH₃CN from 2 to 70% v/v in mixed aqueous solvent. Taft reaction constants, ρ*, obtained from the plots of pK_a^ms against ∑σ* for primary and secondary amines decrease by ca. 0.8 ρ* units with the increase in the CH₃CN content from 2 to 70% v/v. The values of pK_a^ms show an empirical linear relationship with the corresponding values of pK_a^w (where pK_a^w represents the pK_a obtained in aqueous solvent containing 2% v/v CH₃CN), which allows the estimation of a pK_a in mixed H₂O CH₃CN solvents from that in water. © 2000 John Wiley & Sons, Inc. Int J Chem Kinet 32: 146–152, 2000     

Protolytic equilibria of picric acid in a mixture of protophobic and protophilic polar solvents non-donors of H-bonds

A new differentiating medium for the study of prototropic equilibria is proposed: acetonitrile with a small addition of DMSO. From the dependence of the picric acid pK _a on the content of DMSO in this medium the optimum composition of the mixture was found ensuring the stability of the pK _a values with minimal addition of DSMO: 4 wt %. It was experimentally confirmed that the addition of water in an amount up to 0.1 wt % has virtually no effect on the measured pK _a value in a mixture with the optimum composition.     

Paramagnetic probe for molecular interactions: I. EPR and electronic absorption studies of lithium cation solvation by a nitroxide radical

The 2,2,6,6-tetramethylpiperidine nitroxide radical (TMPN) was studied by EPR and electronic absorption spectroscopy in LiClO₄ solutions in various organic solvents. The¹⁴N hyperfine structure, together with the exchange broadening of its components in EPR and the electronic n^* transition in the visible region, provide useful information about Li⁺-TMPN complexes. Both spectroscopic methods prove that the oxygen atom of TMPN was involved in the Li⁺-TMPN interaction. The complex formation constants 15.61, 2.50, 0.75, 0.61, 0.75, and 0.33 dm³-mol^–1 were found in nitromethane, benzonitrile, acetonitrile, propylene carbonate, acetone and tetrahydrofurane, respectively. These formation constants were correlated with donor and acceptor numbers of the solvents and interpreted in terms of competitive Li⁺-TMPN, solvent-Li⁺, and solvent-TMPN interactions.     

Thermodynamics of Solvation of 18-Crown-6 and Its Alkali-Metal Complexes in Various Solvents

Heats of solution of 1,4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6) in acetonitrile, 1,2-dichloroethane, N,N-dimethylformamide, dimethyl sulfoxide, nitromethane, propylene carbonate, pyridine and water were measured at 25 °C and the enthalpies of the transfer of 18-crown-6 from waterto the aprotic solvents were derived. The thermodynamic quantities, G₁°, H₁° and T S₁°, for the formation of the[M(18-crown-6)]⁺ (M⁺ = Na⁺, K⁺, Rb⁺, Cs⁺, NH₄ ⁺) complexeswere determined by titration calorimetry in dimethyl sulfoxide containing0.1 mol dm^-3 (C₂H₅)₄NClO₄ as a constant ionic medium at 25 °C. These thermodynamic quantities suggest that the complexationof 18-crown-6 with the alkali-metal ions mainly reflects the different solvationof 18-crown-6 and also the different degree of solvent structure.     

Thermodynamics of Complexation Reactions of Lithium Ion with Dibenzo-14-Crown-4 and Its Analogs in Nonaqueous Solvents

Formation constants of Li⁺ complexes with 4-substituted dibenzo-14-crown-4 (DB14C4; 4-substituted group: methyl-, tert-butyl-, H-, bromo-, chloro-, formyl-, nitro-) ligands were determined by ⁷Li NMR spectrometry for solutions in nitromethane (NM), acetonitrile (ACN), propylene carbonate (PC), acetone (AC), Pyridine (Py), tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), and N,N′-dimethyl formamide (DMF). Only a 1:1 complex was formed in solvents with a small or medium donor number. The formation constants of these complexes are strongly influenced by the size of the metal ion – the effect of the size of the cavity, by the solvent and by substituent. The stability of lithium ion with different substituents on DB14C4 decreases in the order methyl- > tert-butyl- > H- > bromo- > chloro- > formyl- > nitro- in various solvents. A good Hammett correlation was found by plotting log K_f vs. ∑σ in PC and AC. The extent of the substituent effect increases as the donor number of solvent decreases. The complexes were both enthalpy and entropy stabilized. The same magnitude of ΔS° value for different substituents indicates formation with a similar configuration upon complexation between crown ether and lithium ion. A slight variation in entropy contribution was observable depending on the nature of the alkyl substituent, whereas a large variation in enthalpic contribution shows a remarkable substituent effect upon complexation; the effect can reach 70% in magnitude.