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.     

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.     

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.     

Potentiometric and ab initio studies of acid-base interactions of substituted 4-halo(Cl, Br)pyridine N-oxide systems

By using the potentiometric method, acidity constants have been determined in systems of tri- and tetra-substituted pyridine N-oxides. The potentiometric measurements in systems of four 4-chloropyridine N-oxide derivatives containing the chlorine atom at position 4 to the NO₂ group and four bromine counterparts were carried out in polar non-aqueous solvents, viz. amphiprotic methanol (MeOH) and aprotic protophilic dimethyl sulfoxide (DMSO). It was found that in all the systems studied the pK_a values were readily determinable (as indicated by small standard deviations) in MeOH, whereas in DMSO large standard deviations were obtained making the pK_a values either hardly determinable or indeterminable from potentiometric measurements. Furthermore, it was demonstrated that the acidity constants of protonated N-oxides studied in MeOH changed according to the sequence of their acidity constants in water. It was also found that in the polar solvents studied, i.e. in the amphiprotic methanol and the highly basic aprotic dimethyl sulfoxide, the cationic homo-conjugation equlibrium constants could not be determined using potentiometric method. Also, by using ab initio methods at the RHF and MP2 levels and the PCM model, utilizing the Gaussian 6-31++G^∗∗ basis set, energies and Gibbs free energies of the protonation reactions of the N-oxides have been determined. The energy parameters have been compared with acidity constants of the protonated N-oxides determined by potentiometric titration in methanol to establish a correlation between these approaches.     

UV-spectroscopic study of the influence of traces of water on the protolytic equilibria of substituted pyridine N-oxides in aprotic solvents

Using a UV-spectrophotometric method, an attempt has been made to estimate quantitatively the influence of traces of water in aprotic solvents on the acidic-basic equilibria involving heterocyclic N-oxides. The N-oxides under study were pyridine N-oxide (PyO), 4-methoxy-pyridine N-oxide (4-MeOPyO), and 2-, 3-, and 4-picoline N-oxide (2-, 3-, and 4-PicO). For particular N-oxide the UV-spectra of acetonitrile solutions containing the free base and/or its simple or semiperchlorate have been recorded. To carry out the calculations various equilibrium models which include the protolytic equilibrium with water and basic species present in the solvent have been tested using the program STOICHIO which is based on non-linear regression analysis. It turned out that apart from the acidic-basic dissociation of a protonated N-oxide and cationic homoconjugation (the equilibria which are usually considered in such systems) it is absolutely necessary to take into account the protolytic equilibrium between the cationic acid and water present as impurity. Implications concerning investigations of other equilibrium systems in aprotic solvents and, in particular, the quality of the acidity constants for the calibration agents used in potentiometry are discussed.     

Base Equilibria of Substituted Pyridines in Nitromethane

In the framework of our studies on acid=nbase equilibria in systems comprisingsubstituted pyridines and nonaqueous solvents, acid dissociation constants havebeen determined potentiometrically for a variety of cationic acids conjugatedwith pyridine and its derivatives in the polar protophobic aprotic solvent nitromethane. The potentiometric method enabled a check as to whether and to whatextent cationic homoconjugation equilibria of the BH⁺/B type, as well as cationicheteroconjugation equilibria in BH⁺/B₁ systems without proton transfer, are setup in nitromethane. The equilibrium constants were compared with thosedetermined in water and two other polar protophobic aprotic solvents, propylenecarbonate and acetonitrile. The pK _a values of acids conjugate to the N-bases innitromethane fall in the pK _a range of 5.84 to 17.67, i.e., 6 to 7 pK _a units, onaverage, higher than in water, 1 to 2 units higher than in propylene carbonate,and less than 1 unit lower than in acetonitrile. This means that the basicity ofthe pyridine derivatives increases on going from propylene carbonate throughnitromethane to acetonitrile. Further, it was found that the sequence of the pK _achanges of the protonated amines was consistent in all three media, thus providingthe basis for establishing linear correlations among these values. In the majorityof the BH⁺/B systems in nitromethane, cationic homoconjugation equilibria havebeen established. The cationic homoconjugation constants, log K _BHB+, arerelatively low, falling in the range 1.60–2.89. A comparison of the homoconjugationconstants in nitromethane with those in propylene carbonate and acetonitrile showsthat nitromethane is a more favorable solvent for the cationic homoconjugationequilibria than the other two solvents. Moreover, results of the potentiometricmeasurements revealed that cationic heteroconjugation equilibria were not presentin the majority of the BH⁺/B₁ systems in nitromethane. The heteroconjugationconstant could be determined in one system only, with logdiK _BHB1 + = 2.56.     

Copper(II) complexes of 2-(pyrrolidinomethyl)- and 2-(3-pyrrolinomethyl)pyridine N-oxides

Summary This title pyridine N-oxides have been prepared and their copper(II) complexes isolated as perchlorate, tetrafluoroborate and nitrate salts. The ligands coordinatevia both the pyridine N-oxide oxygen and the amine nitrogen to give bis(ligand) complexes for the perchlorate and tetrafluoroborate salts. The nitrate solids have [CuL(NO₃)₂] stoichiometry with monodentate nitrato-ligands. The spectral properties of these complexes are compared to those of N-alkyl-and N,N-dialkyl2-picolinamine N-oxides as well as other 2-substituted pyridine N-oxides.NATO Fellow on leave from Istanbul Medical Faculty, Istanbul University.     

Direct determination of pKa values of cationic acids conjugated to heterocyclic amine N-oxides in polar aprotic and amphiprotic solvents

The applicability of the direct method of pK_a determination in the case of protonated heterocyclic amine N-oxides in a series of polar non-aqueous (aprotic and amphiprotic) solvents has been tested. The method is based on the pH determination of the non-aqueous solution of complex salt (the semiperchlorate in this case) formed by the N-oxides studied. The direct method not only provides for quick (one data point per each pK_a determined), but also relatively accurate estimates of acidic dissociation constants. It has been experimentally shown on the example of substituted pyridine N-oxides that this method is precise enough in all studied non-aqueous solvents when applied to compounds of not too low basicity (the pK_a being of the order of 5 or higher). To prove this, the pK_a values of protonated monocyclic N-oxides obtained by the direct method have been compared with those resulting from the potentiometric titration curve. The agreement between the results found by using both methods is very good in most cases, the differences being within standard deviations. Based upon this observation it can be inferred that the pK_a values of protonated bicyclic N-oxides in solvents studied determined by using the direct method can be also considered reliable, especially in the case of polar aprotic solvents.     

Simple methods for the estimation of ionization constants of substituted pyridine N-oxides in polar aprotic solvents and water

A direct method for the determination of the pK _a values of acids conjugated to substituted pyridine N-oxides has been proposed which is based on the pH measurement of the solution of the basic salt. It has been experimentally shown that the method is reliable when applied to N-oxides of not too low basicity (pK _a >5). Correlation has been performed between the pK _a values in aqueous and aprotic media solutions which shows the great influence of the solvation effect on the acid-base equilibria. The good correlation between the pK _a values in aqueous and non-aqueous solutions enables the pK _a values in water to be estimated with sufficient accuracy, even in the cases when the experimental limitations make the determination impossible which is shown on the basis of selected examples.     

PMR spectroscopic study of the kinetics of H/D exchange in methyl groups in a series of heterocyclic azines

The rate of H/D exchange among methyl group protons in a series of substituted 3-hydroxypyridines, 5-hydroxypyrimidines, and their N-oxides has been shown to increase with increasing acidity of the medium. The most reactive form of these molecules is the cationic form at pH<2. The rate of H/D exchange of CH₃ group protons in 3-hydroxypyridine derivatives has also been found to be several orders of magnitude lower than the rates of exchange for methyl-substituted 5-hydroxypyrimidine and its N-oxide. Effective rate constants for methyl group proton exchange have been estimated. In the case of methyl-substituted 5-hydroxypyrimidine N-oxide derivatives it has been established that the rate of proton exchange is greater for an ortho-methyl group than for a methyl group in the para-position relative to the N-oxide site.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 93–96, January, 1991.     

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.     

Photochemistry and Photophysics of Papaverine N-Oxide

The photochemistry and photophysics of papaverine N-oxide in polar aprotic and protic solvents has been studied in detail. Complex energy and charge-transfer phenomena between chromophores occur in papaverine. New photochemistry for the papaverine N-oxide system is reported. Irradiation in protic media results in the formation of an emissive charge-transfer state with ensuing intramolecular hydroxylation in high isolated yields (75–80%).     

Investigation of the tautomerism and the intramolecular charge transfer in the series of aromatic N-oxides by electron spectroscopy

The electron spectra of functionally substituted N-oxides of pyridine and quinoline in different solvents have been analyzed. It is shown that the long-wave region of the spectra can be used to investigate the tautomeric forms and the resonance structures of these compounds with substituents which are directly conjugated with the N-oxide group.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1662–1669. December, 1993.     

IR spectroscopic studies on substituted pyridine N-oxide complexes of tin(IV) chloride in acetonitrile

Complexes of eleven substituted pyridine N-oxide donors with stannic chloride in acetonitrile solution were investigated ultizing IR spectroscopy. Two distinct types of behaviour were noted: (1) Pyridine N-oxide donors containing electron releasing substituents generally form strong complexes with SnCl₄ and exhibit maxima in continuous variation plots at a 2:1 ligand-to-metal ratio. Little or no free ligand is detected in these solutions until this ratio is exceeded. Ligands exhibiting this behaviour include the 2-methyl-, 3-methyl-, 4-methyl-, 4-methoxy- and 4-phenylpyridine N-oxides.(2) Pyridine N-oxide donors containing electron neutral to electron with-drawing substituents generally form weaker complexes with SnCl₄ aM exhibit maxima in continuous variation plots at a 1:1 ligand-to-metal ratio. Free ligand is evident in these solutions even at ligand-to-metal ratios as low as 1:3. Formation plots for these complexes indicate the possibility that 1: 2 and 1:1 ligand to metal complexes exist in the concentration ranges studied. Ligands exhibiting this behaviour include the 4-chloro-, 4-nitro-, 3 and 4-acetyl-pyridine N-oxides and 2-pyridine methanol N-oxide.The complex of 2,6-1utidine N-oxide with SnCl₄ exhibits behaviour characteristic of the 1:1 complexes even though the substituents are electron releasing. This ligand contains the most sterically crowded N-O group in the series, however, and steric factors are invoked to explain this behavior.These results are rationalized in terms of an equilibrium model which includes the postulated existence of oxygen bridged dimers comprising a dominant species in solutions containing the 1:1 complexes. Some supporting ¹H NMR and polarographic data are also presented and discussed.     

Solubilization of silica: Synthesis, characterization and study of penta-coordinated pyridine N-oxide silicon complexes

In an effort to design agents that could solubilize silica in water, under ambient conditions and pH, as takes place in nature, novel zwitterionic, penta-oxo-coordinated silicon compounds with siliconate cores have been prepared from 4-substituted pyridine N-oxides (H, OMe, morpholino, NO₂) as donor ligands, their structures established by¹H,¹³C and MS, and the coordination number of silicon, by²⁹Si NMR. The formation of complexes from pyridine N-oxides is noteworthy since they arise from interaction with a weakly nucleophilic oxygen centre. The ability of the pyridine N-oxides to enhance the solubilization of silica in water has been experimentally demonstrated. Possible rationalization of this observation on the basis of O → Si coordination via the oxygen atom of pyridine N-oxide is suggested Dedicated to Professor S Swaminathan on the occasion of his 80th birthday     

Estimation of the total range of 1J(CC) couplings in heterocyclic compounds: pyridines and their N-oxides, the experimental and DFT studies

A very large set of one-bond spin-spin carbon carbon coupling constants, 1J(CC), has been measured for 32 variously mono- and disubstituted pyridine N-oxides and for 14 substituted pyridines. The N-oxides studied were 2-, 3- and 4-monosubstituted isomers, and a series of disubstituted compounds. A variety of substituents has been employed (CH3, COCH3, C5H4NO, CN, F, Br, Cl, OH, OCH3, NH2, N(CH3)2 and NO2), which allowed us to study substituent effects thoroughly. Good linear relationships between 1J(C3C4) in 3- and/or 4-substituted pyridine N-oxides and 1J(CipsoCortho) in benzenes and between 1J(C2C3) in 2- and/or 3-substituted pyridine N-oxides and 1J(CipsoCortho) in benzenes have been found. An analogous linear relationship has been observed between 1J(C3C4) in 3- and/or 4-substituted pyridines and 1J(CipsoCortho) in benzenes. It has been also concluded that, by analogy to 1J(CC) couplings in substituted benzenes, those in pyridines and their N-oxides are the substituent electronegativity dependent. The estimated total range covered by 1J(CC), couplings in substituted compounds varies, in the case of 1J(C2C3) couplings for example, from 25 Hz in 2-lithiopyridine N-oxide to ca. 100 Hz in 2,3-difluoropyridine N-oxide and from 18 Hz in 2-lithiopyridine to 92 Hz in 2,3-difluoropyridine. The DFT calculations have been carried out for the parent compounds and for a set of their 2-lithio, and variously substituted fluoro derivatives. The DFT data reproduced very well the experimental coupling values and revealed that the Fermi contact contribution is the dominating factor which governs the magnitude of the CC coupling across one bond.     

Synthesis of polyamides by ring-opening polyaddition of bis-3,1-benzoxazin-4-ones with aliphatic diamines

Open-chain polyamides with inherent viscosities of 0.1–0.6 were prepared in nearly quantitative yields by the ring-opening polyaddition of combinations of six bis-3,1-benzoxazin-4-one monomers and two aliphatic diamines in polar aprotic solvents at 80°C or below. The polymerization carried out in dimethyl sulfoxide at 80°C was best for preparing high-molecular-weight polymers. These polyamides were generally soluble in polar aprotic solvents, m-cresol, and pyridine.     

Synergistic extraction studies of uranium(VI) and plutonium(VI) with some β-diketones and heterocyclic N-oxides

The equilibrium constants for coordination of methyl substituted pyridine N-oxides with plutonium(VI) thenoyl trifluoroacetonate in chloroform (K_s) follow an order similar to those of the analogous uranium(VI) complexes indicating steric hindrance to bonding in the case of ortho substituted pyridine N-oxides. The extraction constants (k) of Pu(VI) chelates with various β-diketones are found to be only marginally higher than the values for the corresponding uranium(VI) chelates which is in conformity with the close similarity of the ionic radii of PuO ₂ ²⁺ and UO ₂ ²⁺ .     

Quantum-chemical calculations of NMR chemical shifts of organic molecules: VIII. Solvation effects on 15N NMR chemical shifts of nitrogen-containing heterocycles

Effect of solvation on the accuracy of DFT quantum-chemical calculations of ¹⁵N NMR chemical shifts of pyrrole, N-methylpyrrole, and pyridine was studied. The use of continuum model is sufficient to obtain consistent theoretical σ_N values for weakly polar aprotic solvents, whereas solvation effects in strongly polar and protic solvents should be taken into account in the explicit form.