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.     

Epoxidation reaction of perfluoroalkenes with tert-amine N-oxide

Straight-chain aliphatic terr-amine N-oxides were found to be useful oxidizing agent for epoxidation of tri- and tetra-substituted perfluoroalkenes under mild conditions in high yields.The process for epoxidation by employing tri-n-butylamine N-oxide gave the best result in the reagent survey.     

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.     

Distinguishing N-oxide and hydroxyl compounds: impact of heated capillary/heated ion transfer tube in inducing atmospheric pressure ionization source decompositions

In the pharmaceutical industry, a higher attrition rate during the drug discovery process means a lower drug failure rate in the later stages. This translates into shorter drug development time and reduced cost for bringing a drug to market. Over the past few years, analytical strategies based on liquid chromatography/mass spectrometry (LC/MS) have gone through revolutionary changes and presently accommodate most of the needs of the pharmaceutical industry. Among these LC/MS techniques, collision induced dissociation (CID) or tandem mass spectrometry (MS/MS and MS(n)) techniques have been widely used to identify unknown compounds and characterize metabolites. MS/MS methods are generally ineffective for distinguishing isomeric compounds such as metabolites involving oxygenation of carbon or nitrogen atoms. Most recently, atmospheric pressure ionization (API) source decomposition methods have been shown to aid in the mass spectral distinction of isomeric oxygenated (N-oxide vs hydroxyl) products/metabolites. In previous studies, experiments were conducted using mass spectrometers equipped with a heated capillary interface between the mass analyzer and the ionization source. In the present study, we investigated the impact of the length of a heated capillary or heated ion transfer tube (a newer version of the heated capillary designed for accommodating orthogonal API source design) in inducing for-API source deoxygenation that allows the distinction of N-oxide from hydroxyl compounds. 8-Hydroxyquinoline (HO-Q), quinoline-N-oxide (Q-NO) and 8-hydroxyquinoline-N-oxide (HO-Q-NO) were used as model compounds on three different mass spectrometers (LCQ Deca, LCQ Advantage and TSQ Quantum). Irrespective of heated capillary or ion transfer tube length, N-oxides from this class of compounds underwent predominantly deoxygenation decomposition under atmospheric pressure chemical ionization conditions and the abundance of the diagnostic [M + H - O](+) ions increased with increasing vaporizer temperature. Furthermore, the results suggest that in API source decompostion methods described in this paper can be conducted using mass spectrometers with non-heated capillary or ion transfer tube API interfaces. Because N-oxides can undergo in-source decomposition and interfere with quantitation experiments, particular attention should be paid when developing API based bioanalytical methods.     

Thermal oxidative destruction of complexes of heterocyclic N-oxides with Zn(II)tetra-phenylporphyrin

Thermogravimetry, differential thermal analysis and differential scanning calorimetry were applied for investigation of molecular complexes of heterocyclic N-oxide with zinc(II)tetraphenylporphyrin. The kinetic characteristics of the process of the thermal oxidative destruction for individual compounds and their molecular complexes have been calculated. The obtained results indicate that the complex formation of ZnTPhP with heteroaromatic N-oxides leads to an increase of the thermal stability both the metalloporphyrin and the ligands. It has been shown that the stability of the molecular complexes of ZnTPhP with heteroaromatic N-oxides depends on basicity of the coordinated ligand.     

Arylation of pyridine N-oxides via a ligand-free Suzuki reaction in water

We report a practical and highly efficient protocol for the arylation of pyridine N-oxides with arylboronic acid through palladium-catalyzed Suzuki reaction in water.This ligand-free Suzuki reaction is performed in the presence of diisopropylamine and gives 2-or 3-arylated pyridyl N-oxide derivatives in good to excellent yields within 1 h.     

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.     

Spin density distributions in radical anions of heterocyclic amine N-oxides

The unrestricted Hartree-Fock (UHF) method of Snyder and Amos is used to calculate, in the -electron approximation, the spin density distributions in radical anions of heterocyclic amine N-oxides. The computed spin densities are observed to be in good agreement with the experimental values. The computed spin density distribution of the radical anion of pyridine N-oxide is consistent with the greater susceptibility of pyridine N-oxide relative to pyridine to electrophilic nitration. Also, the calculations are consistent with the lower basicity of the N-oxides relative to the parent bases.     

Purification of bacilli ribonucleases by reversed-phase high-performance liquid chromatography

A two-step purification method is presented that utilizes the specific chromatographic properties of bacilli extracellular cycling ribonucleases. A double gradient system of elution is used. Initial concentration of the sample followed by reversed-phase HPLC gives high yields (90–95%) of homogeneous, active protein on both analytical and preparative scales. The procedure may be applied to the isolation of ribonucleases from different sources without significant modifications     

Reaction of 2-pyridyllithium with azine N-oxides. Simple and convenient method for the synthesis of 2,2′-bipyridine 1-oxide and 2,2′:6′,2″:6″2′″-tetrapyridine 1′-oxide

In the reaction of 2-pyridyllithium with quinoline 1-oxide and isoquinoline 2-oxide a nucleophilic substitution of hydrogen occurs to form the corresponding pyridin-2-ylquinolines. A dimerization of the substrate occurs with pyridine 1-oxide, 2,2′-bipyridine 1-oxide or quinoxaline N-oxide. A similar dimerization in good yield occurs when treating azine N-oxides with tert-butyllithium and this serves as a simple and convenient method for preparing bi- and tetrapyridines. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 223–229, February, 2009.     

Cyclocondensation of 3,3-diamino-1-phenylpropenone with pyridine and quinoline N-oxides containing an electrophilic group in position 3

The cyclocondensation of the N-oxide of the methyl ester of nicotinic acid with 3,3-diamino-1-phenylpropenone and the ethyl ester of 3,3-diaminoacrylic acid in the presence of benzenesulfonyl chloride gives the corresponding 2,7-naphthyridines. The cyclocondensation of 3,3-diamino-1-phenylpropene with the N-oxides of dimethyl 3,5-pyridinedicarboxylate and quinolines containing an electrophilic group at in position 3 yields products of the nucleophilic attack of the carbon nucleophilic site of the enediamine at the 2-pyridine ring position, while the amine group binds to the exocyclic electrophilic group. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 578–584, April, 2008.     

Chemical properties of N'-cyanodiazene N-oxides. Reactions involving the nitrile group

The reactivity of the nitrile group in N'-cyanodiazene N-oxides has been examined for the first time. A general approach to the synthesis of nitrogenous functional derivatives of azoxycarboxylic acids by reaction of N'-cyanodiazene N-oxides with nucleophiles (water, alcohol, and hydroxylamine) is described. A method of synthesis of novel azoxy-1,2,4-oxadiazoles and tetrazoles has been developed in which aliphatic, aromatic, or heterocyclic N'-cyanodiazene N-oxides are reacted with benzonitrile N-oxide or sodium azide. Trimerization of N-cyanodiazene N-oxides, catalyzed by anhydrous HCl, has given novel symm-triazines in which the heterocycle bears three diazene N-oxide groups.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1647–1653, July, 1991.     

Turbidimetric determination of sulphate in waters employing flow injection and lead sulphate formation

An analytical flow-injection procedure based on PbSO₄ colloidal formation is proposed as a turbidimetric determination of sulphate in natural waters. Ethanol-water was used as a medium in order to improve the sensibility of the method. Both chemical and flow variables as well as interfering species were studied. A detection limit of 0.3 μg SO²⁻₄ ml⁻¹ was found, and the analytical range (according to Beer's law) was 2–20 μg SO²⁻₄ ml⁻¹. The precision was better than 3% R.S.D. and the sample throughput was ca. 35 h⁻¹. The method, when compared with a standard methodology, gave good results when applied to water analysis.     

N16-oxides of sparteine, 2-methylsparteine and 2-phenylsparteine as ligands; spectroscopic and DFT studies of complexes with ZnX2 (X=Cl,Br)

Six new ZnX₂ (X=Cl, Br) complexes with N16-oxides of sparteine, 2-methylsparteine and 2-phenylsparteine as ligands have been synthesized and characterized by MS, IR, NMR and DFT methods. All complexes have 1 : 1 stoichiometry. Complexation with N16-oxides involves inversion of the configuration at N16, converting ring C from a boat into a chair with the oxygen engaged in coordination. All complexes investigated are of composition [(L–H)⁺(ZnX₃)^?] (where L is N-oxide). The structures of the complexes obtained have been compared with those of the monoperchlorate salts of the N-oxides.     

Controlled thermal degradation for the identification and quantification of amine N-oxides in urine

Studies of amine N-oxides in urine are important for the evaluation of occupational exposure to amines. These thermolabile compounds are difficult to handle by either gas or liquid chromatography, so a device for controlled thermal degradation has therefore been developed. It consists of a short precolumn with shut-off valves at both ends and an aluminum block for heating, and it was connected to the injection port of a gas chromatograph. After injection of amine N-oxides onto the precolumn and thermal degradation, the degradation products were allowed to enter the analytical column. Trimethylamine N-oxide (TMAO) and triethylamine N-oxide (TEAO) were investigated. Their thermal degradation patterns could be used for identification and quantification in aqueous solutions and in urine. Linear calibration graphs based on degradation product peaks (trimethylamine and O,N,N-trimethylhydroxylamine from TMAO and diethylamine and triethylamine from TEAO) were obtained for concentrations up to 500 ppm. Detection limits in aqueous solutions were 0.2 ppm (ca. 1 ng) for TMAO and 1 ppm for TEAO and the precisions were 6% and 9%, respectively. In urine, similar values were obtained for TEAO. The detection limit for TEAO corresponds to the expected concentration in urine after an 8-h exposure to air containing 0.8 mg/m3 of triethylamine.     

Identification of the aromatic tertiary N-oxide functionality in protonated analytes via ion/molecule reactions in mass spectrometers

A mass spectrometric method is presented for the rapid identification of compounds that contain the aromatic N-oxide functional group. This method utilizes a gas-phase ion/molecule reaction with 2-methoxypropene that yields a stable adduct for protonated aromatic tertiary N-oxides (and with one protonated nitrone) in different mass spectrometers. A variety of protonated analytes with O- or N-containing functional groups were examined to probe the selectivity of the reaction. Besides protonated aromatic tertiary N-oxides and one nitrone, only three protonated amines were found to form a stable adduct but very slowly. All the other protonated analytes, including aliphatic tertiary N-oxides, primary N-oxides, and secondary N-oxides, are unreactive toward or react predominantly by proton transfer with 2-methoxypropene.     

反相液相色谱法制备纯化柠檬苦素类似物配糖体

 利用反相制备液相色谱结合吸附树脂柱色谱和离子交换色谱方法 ,从甜橙种子的提取物中纯化制备了一种柠檬苦素类似物配糖体 ,经 NMR测定为奥巴叩酮配糖体。     

Facile one-pot direct arylation and alkylation of nitropyridine N-oxides with Grignard reagents

Facile arylation and alkylation of nitropyridine N-oxides were developed through the reactions of Grignard reagents with nitropyridine N-oxides. For the same 4-nitropyridine N-oxide, arylation occurred at the 2- (or 6-) position, whereas alkylation occurred at the 3-position in an adjustably site-selective manner. The cooperative action of the two groups was discovered in the reactions of 3-nitropyridine N-oxides. This protocol can find wide applications in building various pyridine compounds as illustrated in total syntheses of Emoxipin and Caerulomycin A and E.     

Correlation between the mass-spectrometric behavior and chromatographic mobility of epimeric 4-alkyl-1,2-dimethyl-trans-perhydroquinolol N-oxides

The dependence between the Chromatographic mobility, the character of the disintegration under electron impact, and the configuration at C(₄) was found for epimeric N-oxides of 1,2-dimethyl-4-ethyl-,-4-vinyl-, and -4-ethynylperhydro-4-quinolols. It Is proposed that this dependence be used to determine the configuration at C(₄) in 1,4-dialkyl-trans-perhydro-4-quinolols, from which two epimeric N-oxides can be obtained.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 74–76, January, 1973.