Kinetics of 2,4-dihydro-1,2,4-triazol-3-one nitration in nitric acid

The kinetics and mechanism of 2,4-dihydro-1,2,4-triazol-3-one nitration in nitric acid have been studied. The role of 2-nitro-2,4-dihydro-1,2,4-triazol-3-one as an intermediate has been determined.     

Picryl derivatives of 5-nitro-2,4-dihydro-3H-1,2,4-triazol-3-one

Treatment of 5-nitro-2,4-dihydro-3H-1,2,4-triazol-3-one ( 1 ) with picryl fluoride (PkF) in 1-methyl-2-pyrrolidinone (NMP) gave a mixture of a monopicryl and a dipicryl derivative of 1 in a ratio of 2 :1 , respectively, regardless of the initial concentrations of 1 and PkF. The products were identified as 5-nitro-2-picryl-2,4-dihydro-3H-1,2,4-triazol-3-one ( 2 ) by X-ray crystallography and 5-nitro-2,4-dipicryl-2,4-dihydro-3H-1,2,4-triazol-3-one ( 4 ) by ¹⁵N labeling experiments.     

烷基取代三唑硫酮席夫碱的合成和生物活性研究

用5-烷基-4-氨基-2,4-二氢-1,2,4-三唑-3-硫酮与取代芳醛在酸催化下反应合成了7个席夫碱, 化合物结构用¹H NMR, IR和元素分析进行了表征, 对植物病原菌的生物活性测试表明它们具有较好的生物活性.     

Synthesis of new derivatives of 4-amino-2,4-dihydro-1,2,4-triazol-3-one as potential antibacterial agents

Thirty new 2-substituted-4-amino-5-alkyl or aryl-2,4-dihydro-1,2,4-triazol-3-ones and ten 2-substituted-5-alkyl or aryl-4-(5-nitro-2-furfurylidene)amino-2,4-dihydro-1,2,4-triazol-3-ones were synthesized and characterised by their sharp melting points, elemental analysis, ir and ¹H nmr spectra. These new derivatives of 5-nitro-2-furaldehyde were screened for their antibacterial activities. Most of the compounds showed good activity against one test organism, Staphylococcus aureus. For a few compounds, C.M.I. ranged from 4 to 8 μg/ml (higher results than nitrofurantoin).     

Manipulation of N,O-nucleophilicity: efficient formation of 4-N-substituted 2,4-dihydro-3H-1,2,4-triazolin-3-ones

A new efficient two-step synthesis of 2,4-dihydro-3H-1,2,4-triazolin-3-ones (triazolinones) from readily available amines is reported. Our novel conditions using hexamethyl disilazane, bromotrimethylsilane, and a catalytic amount of ammonium sulfate smoothly cyclize 1-formyl and 1-acetyl semicarbazides to the target triazolinones. This transformation features simultaneous manipulation of N- and O-nucleophilicity as well as differentiation of the nucleophilicity of a urea and an acyl carbonyl.     

Condensation of 5-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione with haloacetic acids

Reactions of triazolethiones with haloacetic acids were studied with 5-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione as an example. It was proved for the first time by X-ray diffraction that the cyclocondensation of these compounds proceeds regiospecifically to give 2-(4-methylphenyl)[1,3]thiazolo[3,2-b][1,2,4]triazol-6(5H)-one rather than its isomer 3-(4-methylphenyl)[1,3]thiazolo[2,3-c][1,2,4]triazol-5(6H)-one.     

Oxidation of aldehyde semicarbazones with lead dioxide: Application to the syntheses of 2-amino-1,3,4-oxadiazoles and 2,4-dihydro-1,2,4-triazol-3-ones

The oxidation of aldehyde semicarbazones with lead dioxide in acid media was effected. The 4,4-disubstituted semicarbazones of aromatic aldehydes afford 2-amino-1,3,4-oxadiazole derivatives. The 2,4-disubstituted semicarbazones give 2,4-dihydro-1,2,4-triazol-3-ones, often in higher yields than the known methods. The mechanisms for the formation of these compounds are proposed.     

Effect of 2,4-dihydro-3H-1,2,4-triazole-3-thiones and thiosemicarbazones on iodide uptake by the mouse thyroid: the relationship between their structure and anti-thyroid activity.

Antithyroid activity of 2,4-dihydro-3H-1,2,4-triazole-3-thiones and thiosemicarbazones was tested by measuring the uptake ratio of thyroid: serum (T/S) of 125I through the mouse thyroid. Substitution with an alkyl group at the 5-position of the triazole nucleus remarkably increased the activity but substitution at the N-2 and/or N-4 positions caused a significant decrease in the activity, indicating the necessity of unsubstituted thioureylene moiety for the antithyroid activity. Thiosemicarbazone derivatives which are an open ring structure of triazoles showed comparable antithyroid activities to those in a ring form, but one thiosemicarbazone showed a much higher toxicity than the corresponding ring form compound. This suggests that the ring structure is not essential for the activity but is necessary to reduce toxic effect. Of fourteen compounds tested, 5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione was the most potent antithyroid compound with low toxicity, with a potency tenfold that of propylthiouracil, a drug currently used.     

Parallel Synthesis of Tetraaryl-4,5-dihydro-1,2,4-triazoles via 1,3-Dipolar Cycloaddition on Soluble Polymer Support

The polymer-supported liquid-phase synthesis of small organic molecules has been a subject of intense research activity. 1,2,4-Triazoles are well known for their antifungal[1] and antibacterial[2] activities. This moiety was also found in potent agonist or antagonist receptor lingands. The synthesis of substituted 1,2,4-triazoles via 1,3-dipolar cycloaddition of imines with nitrilimines is well documented.[3] Herein, we would like to report the first liquid-phase synthesis of 1,3,4,5-tetraaryl-4,5-dihydro-1,2,4-triazoles through a 1,3-dipolar cycloaddition of imines with nitrilimines on PEG support.     

Cu(II), Ni(II) and Fe(II) complexes with a new substituted [1,2,4] triazole Schiff base derived from 4-amino-5-(thien-2-yl ethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one and 2-hydroxy-1-naphthaldehyde: synthesis,characterization and a comparison of theoretical and experimental results by Ab inito calculation

The synthesis and structural properties of two novel compounds, 4-amino-5-(thien-2-yl ethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one and 4-{[(2-hydroxy-1-naphthyl)methyl-ene]amino}-5-(thien-2-ylmethyl) − 2,4-dihydro-3H-1,2,4-triazol-3-one have been described. 4-Amino-5-(thien-2-ylmethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one was synthesized by treating N-propionyl-2-thien-2-ylethane-hydrazonoate with hydrazine hydrate and the Schiff base was obtained from condensation of substituted amine with 2-hydroxy-1-naphthaldehyde. The Cu(II), Ni(II) and Fe(II) complexes were prepared and characterized by elemental analyses, IR, magnetic moment, UV–Vis, mass spectral data and ¹H- and ¹³C-NMR IR spectra. The Schiff base is coordinated to the metal ions in a tridentate manner with OON donors of the phenolic O, carbonyl O and triazolic N. From the magnetic and UV spectral data, it was found the geometrical structure of Cu(II) and Fe(II) ions are octahedral while Ni(II) ion is square planar.Ab-inito 6-31 G* level calculations provided structural information and IR data that were in good agreement with experimental results.     

5-Methyl-4-[3-(2-oxopyrrolidin-1-yl)propyl]-2,4-dihydro-3H-1,2,4-triazol-3-one: Synthesis,Characterization, and DFT Study

Russian Journal of Organic Chemistry - 5-Methyl-4-(3-(2-oxopyrrolidin-1-yl)propyl)-2,4-dihydro-3H-1,2,4-triazol-3-one was synthesized and characterized by X-ray, FTIR and NMR spectroscopic...     

Kinetics of Addition of Alcohols to 3-Aroyl-2,4-dihydro-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones

The kinetics of the reaction of 3-aroyl-2,4-dihydro-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones with aliphatic alcohols in toluene at 25°C were studied by spectrophotometry. The effects of electronic and steric factors in the nucleophile and substrate were estimated by treatment of the kinetic results by the Hammett and Taft equations.     

Conformational analysis of 2,5-diaryl-4-methyl-2,4-dihydro-3H-1,2,4-triazol-3-ones: Multinuclear NMR and DFT calculations

Conformational exploration of five 2,5-diaryl-4-methyl-2,4-dihydro-3H-1,2,4-triazol-3-ones has been carried out based on a combination of their NMR chemical shifts determined in CDCl₃ and the scrutiny of their computed relative energies and absolute shieldings calculated at the DFT/GIAO/B3LYP/6–311++G(d,p) level. The very flat potential energy curves corresponding to the three relevant single bond rotations were explored by calculating the energy of the rotational barriers and comparing the experimental chemical shifts with those theoretically calculated in each rotamer by statistical analysis.     

1,2,4-三嗪类化合物的研究XXI.3-甲硫基-5-氧代-2.5-二氧-1,2,4-三嗪的取代苯磺铣化反应及6- 碳的亲电特性

3-甲硫基-5-氧代-2.5-二氧-1,2,4-三嗪(Ic)与取代的苯磺铣氯反应,在无水吡啶中生成N-[6-(3-甲硫基-5-负氧基)-1,2,4-三嗪基]吡啶内嗡盐(4);在NaOH-H~2O-Ch~3COCH~3中生成3-甲硫基-4-(取代苯磺铣基)-5-氧化-6-羟基-1,4,5,6-四氢- 12,4-(6);资Naoh-Ch~3O中则生成1-(对甲苯磺铣基)-3-甲硫基-6-甲氧基-1,4,5,6-四氢-三嗪(7)显示了其6-C具有不寻常的亲电特性.     

Reactions of fused dihydro-1,2,4-thiadiazoles with isoselenocyanates giving 6aλ4-thia-1,3,4,6-tetraazapentalene derivatives and 5,10-dihydro-1,2,4-thiaselenazolo[4,5-b][2,4]benzodiazepines

3-Methyl-6,7-dihydro-5H-1,2,4-thiadiazolo[4,5-a]pyrimidine (1) reacted with isoselenocyanates with elimination of acetonitrile and concomitant addition of two molecules of the isoselenocyanate to give 2,3-di-substituted-6,7-dihydro-5H-2aλ⁴-thia-2,3,4a,7a-tetraazacyclopent[cd]indene-1(2H),4(3H)-diselones (6a)–(6j). 3-Methyl-5,10-dihydrobenzo[e]-1,2,4-thiadiazolo[4,5-a][1,3]diazepine (3) likewise reacted with alkyl isoselenocyanates to give the 2,3-dialkyl-5-10-dihydro-2aλ⁴-thia-2,3,4a,10a-tetraazapentaleno[3,3a,4-gh]benzocycloheptene-1,4-diselones (9a)–(9h), but reaction of (3) with aryl isoselenocyanates took place with elimination of acetonitrile and incorporation of one molecule of the aryl isoselenocyanate in the product to give 3-arylimino-5,10-dihydro-1,2,4-thiaselenazolo[4,5-b][2,4]benzodiazepines (10a)–(10h). Structure (10) is a new heterocyclic system. The pyrimidine (1) and the diazepine (3) reacted with aryl isoselenocyanates at room temperature in solvents of low polarity to give zwitterion 1:1 addition compounds (7) and (12), respectively. NMR studies reveal that the thiaselenazoles (10) react in solution with aryl isoselenocyanates to give diaryl diselones (11) in a reversible process involving a Dimroth rearrangement. © 1996 John Wiley & Sons, Inc.     

1H and 13C NMR study of 5-substituted-4- (arylidene)amino-2,4-dihydro-3H-1,2,4-triazole-3-thiones and 6-aryl-3-(D-gluco- pentitol-1-yl)-7H-1,2,4-triazolo[3,4-b] [1,3,4]thiadiazines

Five 5-substituted-4-(arylidene)amino-2,4-dihydro-3H-1, 2,4-triazole-3-thiones (2a-2e) and seven 6-aryl-3-(D-gluco-pentitol-1-yl)-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines (3a-3g) were synthesized. The complete 1H and 13C NMR chemical shift assignments were analyzed on one- and two-dimensional NMR techniques, including DEPT, NOE-DIF, COSY, gHMBC, and gHSQC.     

Theoretical and experimental study of the inelastic neutron scattering spectra of β-5-Nitro-2,4-dihydro-3H-1,2,4-triazol-3-one

The inelastic neutron scattering (INS) spectra of β-5-Nitro-2,4-dihydro-3H-1,2,4-triazol-3-one (β-NTO) are presented to 1400 cm⁻¹. The β-NTO vibrational frequencies observed differ considerably from the -NTO vibrational frequencies and normal mode frequency calculations for the isolated molecule. The INS spectrum contains detail unobserved in the previous IR studies, including combinations and overtones of the phonon and internal modes of β-NTO. The INS spectra are compared with periodic DFT calculations to show that the periodic DFT results correctly predict the solid-state molecular vibrational frequencies.     

3,6-二苯氧甲基-1,2,4-三唑并[3,4-b]- 1,3,4-噻二唑衍生物的合成及生物活性

以4-氨基-5-苯氧甲基-3-巯基-1,2,4-三唑与取代苯氧乙酸为原料,三氯氧磷为溶剂,回流反应, 合成了3,6-二苯氧甲基-1,2,4-三唑并[3,4-b]-1,3,4-噻二唑衍生物。通过IR、1H NMR和元素分析确定了各化合物分子结构,并对其进行了室内毒力测试,结果表明此类化合物具有较好的杀菌、抑菌活性。     

Synthesis of derivatives of 1,2,4-triazin-3-thione and 5-amino-2-acyl-2,3-dihydro-1,3,4-thiadiazolium salts from 1,2-dicarbonyl compounds and 4-substituted thiosemicarbazides

The reactions of methyl- and phenylglyoxal with 2,4-disubstituted thiosemicarbazides and of diacetyl with 4-monosubstituted thiosemicarbazides gave monothiosemicarbazones which were converted in trifluoroacetic acid into previously unknown 5-amino-2-acyl-2,3-dihydro-1,3,4-thiadiazolium salts. Diacetyl monosemithiocarbazones are cyclized to 5-methylene-1,2,4-triazin-3-thiones which are also obtained in the reaction ofdiacetyl with 2,4-disubstituted thiosemicarbazides. In particular cases the monothiosemicarbazones are converted into the corresponding 5-alkoxy-1,2,4-triazin-3-thiones in the presence of alcohols. The 3-thio-1,2,4-triazinium cations are formed from the 5-methylene- and 5-alkoxy derivatives in trifluoroacetic acid.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1418–1425, October, 1992.     

Investigation of paths for the synthesis of 5,5-dialkyl-3-perfluoroalkyl-5,6-dihydro-1,2,4-triazolo[3,4-a]isoquinolines

Substituted 3-trifluoromethyl-5,6-dihydro-1,2,4-triazolo[3,4-a]isoquinolines were obtained by the reaction of substituted 1-methylthio-3,4-dihydroisoquinolines with hydrazine hydrate and trifluoroacetic acid. The corresponding 3-perfluoroalkyl derivatives are formed in the course of dehydration of 2-(3,3-dimethyl-3,4-dihydro-1-isoquinolyl)hydrazides of perfluorocarboxylic acids.Institute of Technical Chemistry, Ural Branch, Russian Academy of Sciences, Perm. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 380–386, March, 2000.