Substituted Pyridine N-oxides Research Articles

A Potentiometric Study on Proton-Transfer Equilibria and Cationic Conjugation in Pyridine N-Oxide Systems in Acetone and Methanol

The potentiometric titration method has been used to study the equilibria of cationic in sytems formed by substituted pyridine N-oxides in the polar, non-aqueous solvents acetone and methanol. For comparison, the systems with trimethylamine N-oxide as a representative of aliphatic amine N-oxides and pyridine representing parent heterocyclic amines were also studied. The cationic heteroconjugation constants, i.e. the equilibrium constants for conjugation reactions between free and protonated N-bases leading to the formation of unsymmetric BHB'+ cations, were determined in experimental systems with and without proton transfer. It was found that there were significant differences in the values of the cationic heteroconjugation constants determined in these two acid-base systems. The proton-transfer reactions limit and even preclude the determination of the cationic heteroconjugation constants. On this basis it was concluded that the heteroconjugation constants should be determined in systems without proton transfer. In such systems, in the amphiprotic solvent methanol, cationic heteroconjugation was ascertained in all substituted pyridine N-oxide systems, the values of heteroconjugation constants being relatively low (logarithms of their values of the order of 2-2.5), and only negligible in systems involving trimethylamine N-oxide. A more pronounced tendency towards cationic heteroconjugation of the [OHO]+ type was observed in the aprotic protophobic acetone, where heteroconjugation constants were determined for all amine N-oxide systems studied including those containing protonated trimethylamine N-oxide as a proton donor. However, the values of the cationic heteroconjugation constants were found to be, in methanol likewise, relatively low (log KBHB'+ of the order of 2-3). On the contrary, a greater extent of cationic heteroconjugation equilibria was observed in methanol than in acetone in the case of systems containing pyridine, i.e. [NHO]+ type bridges formed by amine N-oxides and heterocyclic amines. In methanol the heteroconjugation constants turned out to be determinable for all such systems studied (logarithms of the equilibrium constants being of the same order as for N-oxide systems), whereas in acetone the hetero constants were indeterminable for all systems.

Kinetics and mechanism of CO substitution of [η5-CpFe(CO)3]PF6 with PPh3 in the presence of substituted pyridine N-oxide

Abstract The kinetics of substitution reactions of [ η -CpFe(CO) 3 ]PF 6 with PPh 3 in the presence of R-PyOs have been studied. For all the R-PyOs (R = 4-OMe, 4-Me, 3,4-(CH) 4 , 4-Ph, 3-Me, 2,3-(CH) 4 , 2,6-Me 2 , 2-Me), the reactions yeild the same product [ η 5 -CpFe(CO) 2 PPh 3 ]PF 6 , according to a second-order rate law that is first order in concentrations of [ η 5 -CpFe(CO) 3 ]PF 6 and of R-PyO but zero order in PPh 3 concentration. These results, along with the dependence of the reaction rate on the nature of R-PyO, are consistent with an associative mechanism. Activation parameters further support the bimmolecular nature of the reactions: ΔH ≠ = 13.4 ± 0.4 kcal mol −1 , ΔS ≠ = −19.1 ± 1.3 cal k −1 mol −1 for 4-PhPyO; ΔH ≠ = 12.3 ± 0.3 kcal mol −1 , ΔS ≠ = 24.7 ±1.0 cal K −1 mol −1 for 2-MePyO. For the various substituted pyridine N -oxides studied in this paper, the rates of reaction increase with the increasing electron-donating abilities of the substituents on the pyridine ring or N -oxide basicities, but decrease with increasing 17 O chemical shifts of the N -oxides. Electronic and steric factors contributing to the reactivity of pyridine N -oxides have been quantitatively assessed.

FT-IR, UV—visible and X-ray studies of complexes of pyridine N-oxides with pentachlorophenol

The crystal structure of the 4-methoxy-2,6-dimethylpyridine N-oxide·pentachlorophenol complex has been determined by X-ray analysis. The O ··· O distance is 2.439(6) Å, the OHO angle is 152.3° and the hydrogen-bonded proton is close to the phenol molecule. The FT-IR spectra of pentachlorophenol complexes with some substituted pyridine N-oxides in the solid state and seven aprotic solvents of different polarity (ϵ from 2.27 to 37.5) show a broad absorption. The broad absorption shows weak dependence upon solvent polarity and is classified as type (ii). UV spectra show that in the investigated complexes protons are not transferred from the phenol to the N-oxides. Formamide ( ϵ = 111) is a much stronger proton acceptor than the pyridine N-oxides. Pentachlorophenol in formamide is converted to the phenolate ion.

The Boekelheide Reaction: Trifluoroacetic Anhydride as a Convenient Acylating Agent

Abstract 2-Alkyl substituted pyridine N-oxides react with trifluoroacetic anhydride at room temperature to give selectively and with high yields the corresponding 2-(α-hydroxyalkyl)-pyridines.

The molecular complex of 4-(N-pyridinium)pyridine-N-oxide chloride with tetracyanoethylene in the synthesis of substituted pyridine N-oxides

The structure of the complex of 4-(N-pyridinium)pyridine-N-oxide chloride with tetracyanoethylene was studied by13C NMR spectroscopy. The results of the investigation, suggesting the use of this complex in the synthesis of substituted pyridine derivatives, were conformed experimentally by its reaction with oxygen and with nitrogen-containing nucleophiles.

Acid-Base Equilibria of Substituted Pyridine N-Oxides in N,N-Dimethylformamide and Dimethyl Sulfoxide

Acidity constants have been determined potentiometrically for a variety of conjugate acids of substituted pyridine N-oxides in N,N- dimethylformamide ( dmf ) and dimethyl sulfoxide ( dmso ). The pKa values in these solvents varied in the same direction and correlated with the pKa values of these species in water and in the protophobic aprotic solvent acetonitrile. Further, a linear relationship has been established between the pKa values in the two protophilic aprotic solvents under study. The most basic substituted pyridine N-oxides exhibited a weak tendency towards cationic homoconjugation in dmf , whereas in the more basic dmso the homoconjugation equilibrium was not established for any of the heterocyclic N-oxides. The phenomenon of cationic homoconjugation was also not observed with pyridine as a representative of heterocyclic amines, both in dmf and dmso. This finding complies with the results obtained in other polar aprotic solvents.

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 pKa 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.

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.

Acid–base and cationic homoconjugation equilibria in nitromethane solutions of substituted pyridine N-oxide systems

The acid-dissociation and cationic-homoconjugation constant values for nine substituted pyridine N-oxide systems in nitromethane have been determined by the potentiometric titration method. A series of N-oxides having a wide spectrum of acid–base properties (aqueous pKa values in the range 3.88 to –1.7) has been studied. A linear relationship, between the nitromethane and the aqueous pKa values, pKNMa= 1.64 pKWa+ 7.41, has been found. As in other polar aprotic solvents, cationic homoconjugation has been demonstrated in nitromethane. The homoconjugation constants are higher than those in acetonitrile and increase with increasing basicity of the N-oxides. The relationship between the logarithms of the homoconjugation constants and the nitromethane pKa values can be expressed by the equation: log KBHB+= 0.39 pKa+ 0.33. The tendency of substituted pyridine N-oxides towards cationic homoconjugation in nitromethane has been found to be comparable with that of bicyclic amine N-oxides and is ca. two orders of magnitude stronger than that of the parent amines. The applicability of the direct method of pKa determination of substituted pyridine N-oxides in nitromethane solutions has been proven. Using this method, the pKa values of an extended series of eleven pyridine N-oxide derivatives have been estimated and compared with those calculated from a complete titration curve.

Localization of the proton in complexes of trifluoroacetic acid with pyridine N-oxides in dichloromethane by second-derivative infrared spectroscopy

A single carbonyl band in the second-derivative FTIR spectra of the equimolar mixtures of six substituted pyridine N-oxides with trifluoroacetic acid in dichloromethane implies that complexation is complete and hydrogen bonds are described by a strongly asymmetrical quasi-single minimum potential. The equimolar complexes interact with a second molecule of the acid, the second hydrogen bond causes only a minor effect on the first hydrogen bond and this effect is independent of proton-acceptor properties of N-oxides. The equimolar complexes interact also with a second molecule of N-oxide to form homoconjugated complex (BHB)+A–. This interaction is controlled by pKa of the N-oxide.

Evidence for a single minimum potential for hydrogen bonds of pyridine N-oxide complexes with dichloroacetic acid in dichloromethane

FTIR spectra of dichloracetic acid and its eight complexes with substituted pyridine N-oxides and N,N-dimethylaniline in dichloromethane-d 2 are reported. 4- N,N-dimethylaminopyridine N-oxides form two types of complexes with dichloroacetic acid; the acid interacts with NO or Me 2N groups. The shape of the second derivative of absorption in the carbonyl region implies that the hydrogen bonds are described by a strongly asymmetrical quasi-single minimum potential. The situation with regard to the observed carbonyl frequencies as related to conformational equilibria is reviewed.

Differentiation of substituent effects from hydrogen bonding and protonation effects in carbon-13 NMR spectra of pyridine N-oxides

Aromatic 13C chemical shifts are reported for 4-substituted and 3-substituted pyridine N-oxides measured in deuteriochloroform, deuterium oxide, perchloric acid (60% in D2O) and dichloroacetic acid (80% in CDCl3), and also for O-alkylated derivatives in (CD3)SO and D2O. The substituent chemical shift (SCS) data show systematic non-additivity in comparison with monosubstituted benzenes. Data for the position para to the variable substituent were analysed by means of the dual substituent parameter equation. For this position multiple substituent interactions are responsible for the non-additive shifts; interactions have both an inductive (polar) and a resonance component. Hydrogen bonding and protonation effects were differentiated from the substituent effect. It is shown that the relative 13C chemical-shift difference [(Δ3–Δ4)/Δ3] is a measure of the hydrogen bond and protonation effects and is not subject to substituent effects. 3-Dimethylaminopyridine N-oxide is protonated at the dimethylamino group, but 4-dimethylaminopyridine N-oxide at the oxygen.

Acid–base and cationic homoconjugation equilibria of substituted pyridine N-oxides in acetone

The pKa and cationic homoconjugation constants in acetone have been determined for a series of eight pyridine N-oxide derivatives with a wide spectrum of acid–base properties. The acetone pKa values were found to correlate well with the aqueous ones. The values are lower than those determined in acetonitrile and benzonitrile, owing to the higher basicity of acetone. As in other aprotic solvents, cationic homoconjugation was found to take place for sufficiently basic N-oxides (pKa > 5 in acetone). In contrast to anionic homoconjugation the homoconjugation constants are lower in acetone than in nitriles. For comparison, investigations were carried out for pyridine, showing the homoconjugation constant to be indeterminable which conforms with the results obtained in other aprotic solvents.

Experimental studies on the UV spectra of substituted pyridine N-oxides in methanol

Experimental studies on the UV spectra of substituted pyridine N-oxides in methanol

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.

Influence of the conjugation effect on the UV-spectra of 4-substituted pyridine N-oxides and their conjugated acids

The UV-spectra of three 4-substituted pyridine N-oxides: 4-methoxy pyridine N-oxide, 4-N′,N′-dimethylamine pyridine N-oxide, and 4-nitro pyridine N-oxide, as well as their simple cations in acetonitrile have been compared with the results of CNDO/S-CI calculations, in order to make possible the assignment of bands. For 4-N′,N′-dimethylamine and 4-methoxy derivatives both N-oxide oxygen and substituent protonated forms were considered. It has been found that in all cases except the 4-methoxy derivative conjugation with the substituent influences greatly the transitions of the free and N-oxide oxygen protonated N-oxides. The spectra of the substituent protonated N-oxides resemble that of free pyridine N-oxide which in comparison with the experimental data may indicate the preference of N-oxide oxygen protonation.

Relationship between the Electronic Structure and Acidic-Basic Properties of 4-Substituted Pyridine N-Oxides

CNDO/2 and MNDO calculations on pyridine N-oxide (PyO), 4-nitro- (4 NO2PyO), 4-methyl-(4 PicO), 4-methoxy- (4 MeOPyO), and 4-N′,N′ -dimethylamine-pyridine N-oxide (4 N′,N′Me2PyO) and on their protonated forms have been carried out. Unknown geometries have been obtained by optimization of the MNDO energy. It has been shown that for 4 NO2PyO, 4 MeOPyO, and 4 N′,N′Me2PyO N-oxide oxygen protonated forms are much more energetically stable than the forms protonated on substituents. The calculated ionization potentials and dipole moments of the compounds studied are in good agreement with the experimental data. Both CNDO/2 and MNDO protonation energies correlate well with the experimental pKa values determined in four different solvents: acetonitrile, propylene carbonate, nitromethane, and water, the slopes being however much less than unity which indicates the important role of the solvation effect. Based on the parameters of the correlations obtained the protolytic and solvation properties of the solvents studied have been discussed.

New description of the substituent effect on electronic spectra by means of substituent constants—VI. Utraviolet spectra of 4-substituted pyridine N-oxides and blue shifted iodine bands of their EDA complexes with iodine

Electronic spectra of 4-substituted pyridine N-oxides and their EDA complexes with iodine were studied. The substituent effect on the near u.v.1A1 intramolecular CT bands of the N-oxides and on the blue shifted iodine bands caused by CT complex formation are discussed in terms of a general equation, theoretically derived in order to describe the substituent effect on electronic spectra by means of substituent constants. The results are quite successful and supported by semi-empirical SCFMO-CI calculations. Based on the results mentioned above, the character of n-σ type N-oxide—iodine CT complexes is also examined. The complex formation constants (log K) and pKa values of the N-oxides correlate especially well, indicating that the CT interaction mechanism cannot be neglected in proton addition reactions such as hydrogen bonding and pKa values.

Experimental studies on the UV-spectra of substituted pyridine N-oxides and their perchlorates in acetonitrile

Simple and, if formed, semiperchlorates of substituted pyridine N-oxides have been synthesised and the spectra of N-oxides and salts have been recorded in acetonitrile solution. For basic enough N-oxides homoconjugated cations are observed spectrophotometrically while for the remaining ones such individuals have not been observed even for large concentrations of salts. In the spectra of substituted pyridine N-oxides and their proton complexes the same bands can be noted as for pyridine N-oxide and its complexes with proton. For N-oxides containing groups which can exert some mesomeric effect the characteristic N-oxide redox band observed for pyridine N-oxide at 275 nm is strongly red-shifted, owing to conjugation.

Complexes of Tlcl2I with Pyridine N-Oxide and some Substituted Pyridine N-Oxides

Abstract The following compounds: TlCl2I. (PyO)2, TlCl2I. (2-PicO)2, TlCl2I. (3-PicO)2, TlCl2I. (4-PicO)2, TlCl2I. and TlCl2I. (4-MeOPyO)2 have been prepared and characterized by elemental analysis. The solids are monomers and behave as non-electrolytes in acetonitrile solution. The molecular structures of the complexes were studied on the basis of 1H NMR and IR spectra. The most probable structure is that of a trigcnal bipyramid with the halogen atoms in equatorial positions and the two ligands L in axial positions.