Chromatographic and electrophoretic determination of thioamides based on thiazole, 1,3,4-thiadiazole, 1,2,4-triazole,and tetrazole

A procedure was developed for the determination of the following thioamides based on thiazole, 1,3,4-thiadiazole, 1,2,4-triazole, and tetrazole: 2-mercaptothiazole (I), 2-mercapto-1,3,4-thiadiazole (II), 2-mercapto-5-methyl-1,3,4-thiadiazole (III), 3-mercapto-1,2,4-triazole (IV), 3-mercapto-4-methyl-1,2,4-triazole (V), and 5-mercapto-1-methyltetrazole (VI). The determination was performed by reversed-phase HPLC on a column (150 × 4 mm) packed with Diaspher-110-C18 (5 μm) using elution with an acetonitrile-acetate buffer solution (pH 4.70) mixture (5: 95). Detection was performed at the light absorption maximums of compounds I (320 nm), II (305 nm), III (310 nm), IV (260 nm), V (254 nm), and VI (245 nm). The calibration graphs were linear over the following concentration ranges (μg/mL): 0.47–11.72 (I), 0.47–11.82 (II), 0.53–13.22 (III), 0.40–10.11 (IV), 0.46–11.52 (V), and 0.46–11.62 (VI). The limits of detection were 0.45, 0.43, 0.50, 0.37, 0.41, and 0.42 μg/mL for compounds I–VI, respectively. Conditions for the separation of a mixture of compounds I and III–V and for the quantitative determination of compounds I–VI by capillary zone electrophoresis (CZE) were optimized. CZE was performed on a quartz capillary of size 60 cm (effective length of 50 cm) × 75 μm at a voltage of 20 kV with a borate buffer solution (pH 9.18). The procedure allowed us to evaluate the concentrations of substances in the ranges of 1.17–93.75 (I), 1.18–94.54 (II), 1.32–105.76 (III), 1.01–101.13 (IV) 1.15–115.16 (V), and 1.16–116.15 (VI) μg/mL with the detection limits of 1.10, 1.11, 1.20, 0.96, 1.01, and 1.02 μg/mL for compounds I–VI, respectively.     

Pyridylethylation of cyclic thioamides and amides. I. Pyridylethylation in the tetrazole and 1, 2, 4-triazole series

1-Aryltetrazoline-5-thiones and 4-aryl-1, 2, 4-triazolyl-3-thiones which are cyclic amides and potential mercapto compounds have been 2-pyridylethylated for the first time. It is shown that in the compounds prepared the 2-pyridylethyl-2 group is on the nitrogen atom of the thioamide group, so that the above compounds react as thiones.     

Synthesis and structure of new ditopic ligands containing tetrazole and 3-nitro-1,2,4-triazole fragments

Alkylation of 3-nitro-1,2,4-triazole with haloalkyltetrazoles has afforded in high yields previously unknown 1-[2-(3-nitro-1H-1,2,4-triazol-1-yl)ethyl]-1H-tetrazole and 2-tert-butyl-5-(3-nitro-1H-1,2,4-triazol-1-ylmethyl)-2H-tetrazole. The molecular and crystal structure of these compounds has been established by X-ray diffraction analysis (XRD).     

Investigations in the 1,2,4-triazole series

To select a method for the synthesis of the previously difficulty accessible 5-bromo-1-phenyl-1,2,4-triazole (I) and 1-phenyl-1,2,4-triazoline-5-thione (II), a MO LCAO calculation has been carried out in Huckel's approximation of the energies of the radical, electrophilic, and nucleophilic localization on the various carbon atoms of 1-phenyl-1,2,4-triazole (III). In accordance with this calculation, the required compounds have been obtained in good yields by reactions taking place by a radical mechanism: I by bromination with bromosuccinimide and II by the direct thionation of III. The high reactivity of the bromine atom in position 5 has been noted.For part VIII, see [1].     

Synthesis and structure of some diazonium salts of the 1,2,4-triazole series

Diazotriazolecarboxylic acid, its methyl ester, and 3-diazonium-5-nitrophenyltriazoles have an internal salt structure. 3-Diazonium-5-methyl- and -5-phenyl-1,2,4-triazoles have been isolated as nitrates, perchlorates, and fluoroborates. All the compounds mentioned exist in strongly acid media as salts of the corresponding acid with diazo cations, but in weakly acid and neutral solutions they exist as zwitterions, formed by elimination of a proton from the imino nitrogen of the heterocycle.Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 6, No. 5, pp. 705–709, May, 1970.     

Molecular structure of 1,2,4-triazole

The molecular structure of 1,2,4-triazole has been determined by gas phase electron diffraction. The intemuclear distances and bond angles were obtained by applying a least-squares analysis to the experimental intensity. The bond distances (r_g) and bond angles were N₁-N₂ = 1.380 ± 0.010 Å, N₂C₃ = 1.329 ± 0.009 Å, C₃-N₄ = 1.348 ± 0.009 Å, N₁-C₅ = 1.377 ± 0.004 Å, N₄C₅ = 1.305 Å (calculated value). N-H = 0.990 Å, C-H = 1.054 Å, ∠N₁N₂C₃ = 102.7± 0.5°, ∠N₂C₃N₄ = 113.8 ± 1.3°, ∠N₂N₁C₅ = 108.9 ± 0.8°, ∠H₁N₁N₂ = 110.9°, ∠H₂C₃N₄ = 119.2°, ∠H₃C₅N₁ = 131.0°, ∠C₃N₄C₅ = 105.7° (calculated value) and ∠N₄C₅N₁ = 108.7° (calculated value).     

Synthesis and transformation of acids of the 1,2,4-triazole series

It is shown that a mixture of 1,2,4-triazole-3,5-dicarboxylic acid and 3-methyl-1,2,4-triazole-5-carboxylic acid is formed by oxidation of 3,5-dimethyl-1,2,4-triazole with insufficient oxidizing agent. Some derivatives of 3-methyl-1,2,4-triazole-5-carboxylic acid were obtained.See [1,2] for Communication II.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1695–1696, December, 1970.     

Vibrational spectra and structure of 1,2,4-triazole derivatives

The frequencies and forms of the normal vibrations of the anions of 1,2,4-triazole and 3-nitro-, 3-nitro-5-methyl-, and 3,5-dinitro-1,2,4-triazoles were calculated. The potential energy constants were calculated by solution of the reciprocal spectral problem, and the frequencies in the experimental spectra were assigned to the fundamental types of normal vibrations. It is shown that the nitro groups in the 3 and 5 positions in the anions of the triazoles are located in the plane of the triazole ring. The coordination of the metal in crystalline salts of nitrotriazoles was studied by the methods of vibrational spectroscopy, and an assumption is stated that the most probable position of the metal is near the oxygen atoms of the nitro group along the Me-O-N line. As a result of a theoretical analysis of the vibrational spectra of the anions it was ascertained that equalization of the lengths of the ring CN bonds does not occur during ionization of the covalent triazoles. Calculations by the MO LCAO SCF method are in agreement with the data from vibrational spectroscopy.See [1] for communication III.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1423–1431, October, 1973.     

Vibrational spectra and structure of 1,2,4-triazole derivatives

From an analysis of the IR and Raman spectra and a calculation of the frequencies and forms of the normal vibrations of the nitrotriazoles, conclusions have been drawn on the structure of 3,5-dinitro-1,2,4-triazole and 1-methyl-3,5-dinitro-1,2,4-triazole. The nitro group in position 3 of the triazole ring is located in the plane of the molecule, and that in position 5 is rotated about the CN bond. The spatial nonequivalence of the nitro groups leads to the splitting of the absorption bands in the IR spectra that are characteristic for the anti- and synphase vibrations of the nitro groups.For Communication (II), see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1194–1198, September, 1973.     

Vibrational spectra and structure of 1,2,4-triazole derivatives

The frequencies and forms of the normal vibrations of 3-nitro-1,2,4-triazole, its 1-deuteroand 1-methyl derivatives, and 1-methyl-3-nitro-5-chloro(bromo)-1,2,4-triazole, which are classified as having C_S group symmetry, were calculated. The potential energy constants were refined by solution of the reciprocal spectral problem, and the frequencies in the experimental spectra were assigned to the principal types of vibrations.See [1] for communication I.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 707–712, May, 1973.     

Chemical,physicochemical and crystallographical studies in the 1,2,4-triazole series

The structure of the condensation product of 1,2,4-lriuzole and morpholinochloroethane was determined by comparison of its chemical, physicoehemieal and erystallographical characteristics with those of two isomeric compounds prepared by an univocal synthesis.     

Studies in the 1,2,4-triazole series. III. Aminomethylation of 4-phenyl-1,2,4-triazolinethione-3

In a study of the aminomethylation of 4-phenyl-1,2,4-triazolinethione-3 (TRIT) it is ascertained that the reaction involves the nitrogen atom of the thioamide group. Salts of TRIT with secondary amines are obtained. It is shown that replacement of N (2) in 1-phenyltetrazolinethione-5 by the=CH- of TRIT leads to a decrease in the acidity of the thione and an increase in the stability of the hydroxymethyl and chloromethyl derivatives.For preceding papers see [1] and [2].     

High-performance liquid chromatographic assay of sulbactam using pre-column reaction with 1,2,4-triazole

A high-performance liquid chromatographic (HPLC) method for the determination of sulbactam in human and rat plasma and urine has been developed. Sulbactam was reacted with 1,2,4-triazole to yield a product having an ultraviolet absorption maximum at 326 nm. The product was separated using reversed-phase HPLC from the regular components of plasma and urine with an ion-pair buffer at 50 degrees C and detected at the ultraviolet maximum. The limits of accurate determination were 0.2 and 1.0 micrograms/ml in plasma and urine, respectively. The coefficients of variation of inter- and intra-assays in human plasma spiked at 4.0 micrograms/ml (n = 5) were 1.02 and 3.05%, respectively. Coexisting cefoperazone, penicillins, or the alkaline degradation product(s) of sulbactam did not interfere in the sulbactam assay. The pharmacokinetic behaviour of sulbactam and cefoperazone coadministered to rats was estimated by moment analysis.     

Unusual reaction of 3-amino-1,2,4-triazole with 1,3-diiodopropan-2-one

3-Amino-1,4-bis(2-oxopropyl)-4H-1,2,4-triazolium triiodide is the product of the reaction of 3-amino-1,2,4-triazole with 1,3-diiodopropan-2-one in acetone in the absence of bases and phase-transfer catalysts. In dimethyl sulfoxide, conversely, a water soluble polyionene consisting of three aminotriazole rings bound by 1,3-dimethylenecarbonyl bridges is formed. The effect of the solvent on the alkylation of 3-amino-1,2,4-triazole with 1,3-diiodopropan-2-one was studied.     

A novel N-N bond cleavage reaction of 4-amino-1,2,4-triazole derivatives

5-Substituted-4-amino-3-thiol-1, 2, 4-triazoles (1a- b) react with orthonitrochloro- benzene or para-nitrochlorobenzene to give N-N bond cleavage products 2a-d, one structure of which (2b) has been unambiguously confirmed by an X-ray structural analysis.