Synthesis of 4-hydroxy-4,5-dihydro-1,2,4-triazol-5-ones

Summary A series of hydroxamic acid ethoxycarbonylhydrazides was obtained by reactions of ester ethoxycarbonylhydrazones with hydroxylamine. The corresponding 3-substituted 4-hydroxy-4,5-dihydro-1,2,4-triazol-5-ones were synthesized by cyclization of these hydroxamic acid derivatives in basic medium.

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Synthesen von 4-Hydroxy-4,5-dihydro-1,2,4-triazol-5-onen

Zusammenfassung Durch Reaktion von Esterethoxycarbonylhydrazonen und Hydroxylamin wurde eine Reihe von Hydroxamsäureethoxycarbonylhydraziden gewonnen; Cyclisierung dieser Verbindungen durch Base gab die entsprechenden 3-substituierten 4-Hydroxy-4,5-dihydro-1,2,4-triazol-5-one.

     

Synthesis of 4-amino-4,5-dihydro-1H-1,2,4-triazole-5-ones and their isatin-3-imine derivatives

Iminoester hydrochlorides 1 have been synthesized. These compounds were then converted into ester ethoxycarbonyl hydrazones 2, from which in turn a new series of substituted 4-amino-4,5-dihydro-1H-1,2,4-triazole-5-ones, 3, was then prepared.Finally a set of isatin imine derivatives 4 was obtained from the reaction of compounds 3 with isatin. The structures of all the new synthesized compounds were confirmed by elemental analyses, IR, (1)H-NMR and (13)C-NMR spectra.     

Synthesis and non-aqueous medium titrations of some new 4-benzylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives

The synthesis of 3-alkyl(aryl)-4-(3-ethoxy-4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones 3 from the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones 2 with 3-ethoxy-4-hydroxybenzaldehyde is described.The acetylation and methylation reactions of the compounds 3 giving compounds of type 4 and 5, respectively, were investigated. The newly synthesized compounds were characterized using elemental analyses and IR, (1)H-NMR, (13)C-NMR and UV spectral data.In addition, to investigate the effects of solvents and molecular structure upon acidity,compounds 3 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents (isopropyl alcohol, tert-butyl alcohol, acetonitrile and N,N-dimethylformamide). The half-neutralization potential values and the corresponding pKa values were determined for all cases.     

Synthesis of 3-(3-Alkyl-5-thioxo-1H-4,5-dihydro-1,2,4-triazol-4-yl)aminocarbonylchromones

A series of 3-(3-alkyl-5-thioxo-1H-4,5-dihydro-1,2,4-triazol-4-yl)aminocarbonylchromones has been prepared by oxidation of 3-formylchromone with Jones' reagent followed by reaction with 3-alkyl-4-amino-4,5-dihydro-1,2,4-triazole-5(1H)-thione in the presence of POCl³. The structures of the compounds were confirmed by IR, LC-MS, and ¹H NMR spectra and elemental analyses.     

Synthesis of Schiff and Mannich bases of isatin derivatives with 4-amino-4,5-dihydro-1H-1,2,4-triazole-5-ones

Ethyl imidate hydrochlorides 1 were prepared by passing HCl gas through solutions of substituted benzyl cyanides and absolute ethanol. Ethoxycarbonylhydrazones 2 were synthesized from the reaction of compounds 1 with ethyl carbazate. Treatment of 2 with hydrazine hydrate leads to the formation of substituted 4-amino-4,5-dihydro-1H-1,2,4-triazole-5-ones 3. Isatin and 5-chloroisatin were added to 3 to form Schiff bases 4 and N-Mannich bases 5 of these compounds were synthesized by reacting with formaldehyde and piperidine. Their chemical structures were confirmed by means of IR, (1)H- and (13)C-NMR data and by elemental analysis.     

Synthesis, acidity and antioxidant properties of some novel 3,4-disubstituted-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives

3-Alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones 2a-g reacted with 4-diethylaminobenzaldehyde to afford the corresponding 3-alkyl(aryl)-4-(4-diethyl-aminobenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones 3a-g. The acetylation reactions of compounds 3a-e were investigated and compounds 4a-e were thus obtained. The new compounds were characterized using IR, (1)H-NMR, (13)C-NMR, UV and MS spectral data. In addition, the newly synthesized compounds 3a-g were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents such as isopropyl alcohol, tert-butyl alcohol, acetone and N,N-dimethylformamide (DMF), and the half-neutralization potential values and the corresponding pKa values were determined for all cases. Moreover, 3 and 4 type compounds were also screened for their antioxidant activities.     

Efficient synthesis of 5-substituted-4,5-dihydro-1,2,4-triazin-6-ones and 5-substituted-1,2,4-triazin-6-ones

Treatment of methyl α-(dimethylarninomethyleneamino)carboxylates 1 (from α-amino acids and dimethylformamide dimethylacetal) with hydrazine gives 5-substituted-4,5-dihydro-1,2,4-triazin-6-ones 2 , which are smoothly dehydrogenated to 5-substituted-1,2,4-triazin-6-ones 3 with potassium permanganate in acetone/acetic acid.     

Mass-spectrometric study of 5,6-dihydro-4H-1,3-oxazin-5-ones

Under the influence of electron impact, 2-aryl-1,3-oxazin-5-ones undergo fragmentation primarily with the elimination of the C₂H₂O₂ group of atoms, as well as with the formation of aroyl cations. The complete absence of the retrodiene fragmentation that is characteristic for such heterocyclic systems makes it possible to conclude that the double bond in the heteroring is not stabilized. In the case of 4-alkyl- and 4-benzyl-substituted oxazinones the molecular ions under-go rearrangement, as a result of which a seven-membered heteroring is formed due to inclusion of the methylene group of the substituent in an oxazine ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 43–47, January, 1981.     

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.     

Synthesis and determination of pKa values of some new 3,4-disubstituted-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives in non-aqueous solvents

3-Alkyl(Aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (2) reacted with 2-furoyl chloride and thiophene-2-carbonyl chloride to afford the corresponding 3- alkyl(aryl)-4-(2-furoylamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (3) and 3-alkyl(aryl)- 4-(2-thienylcarbonylamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (4), respectively. The new compounds synthesized were characterized by using IR, 1H-NMR, 13C-NMR and UV spectral data together with elemental analysis. In addition, to investigate the effects of solvents and molecular structure upon acidity, compounds 3 and 4 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents (isopropyl alcohol, tert-butyl alcohol, N,N-dimethylformamide and acetonitrile). The half-neutralization potential values and the corresponding pKa values were determined for all cases.     

3-Azido-N-nitro-1H-1,2,4-triazol-5-amine-based energetic salts

Twelve energetic nitrogen‐rich salts based on 3‐azido‐N‐nitro‐1H‐1,2,4‐triazol‐5‐amine were prepared and fully characterized by ¹H, ¹³C NMR, and IR spectroscopy, differential scanning calorimetry (DSC), and elemental analysis. The crystal structures of the neutral compound 3‐azido‐N‐nitro‐1H‐1,2,4‐triazole‐5‐amine ( 1 ) and its triaminoguanidinium salt ( 13 ) were determined by single‐crystal X‐ray diffraction. The density of 1 and its twelve salts ranged from 1.57 to 1.79 g cm^?3, and the heat of formation was calculated with the Gaussian 03 suite of programs. Compounds 1 – 13 exhibit promising detonation performances (pressure: 25.3–39.3 GPa; velocity: 8159–9409 ms^?1; EXPLO 5.05). Impact sensitivities were also determined by hammer tests and resulted ranging from 2.5 J (very sensitive) to >40 J (insensitive).     

Synthesis of 4-Amino-6-R-4,5-dihydro-3-phenacylthio-1,2,4-triazin-5-ones and 8H-3-R-7-Aryl-1,2,4-triazino[3,4-b][1,3,4]thiadiazin-4-ones

A study was carried out on the reaction of 4-amino-6-R-2,3,4,5-tetrahydro-3-thioxo-1,2,4-triazin-5-ones with halo ketones in alkaline media to yield 4-amino-6-R-4,5-dihydro-3-phenacylthio-1,2,4-triazin-5-ones, which then convert to 8H-3-R-7-aryl-1,2,4-triazino[3,4-b][1,3,4]thiadiazin-4-ones.     

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.     

Synthesis of 1,4-dihydro-4-methyl-1-phenyl-5H-1,3,4-benzotriazepin-5-ones

The synthesis of 1,4-dihydro-4-methyl-1-phenyl-5H-1,3,4-benzotriazepin-5-one ( 4a ) and its 8-chloro analog ( 4b ) is described. Attempted synthesis of the 2-methyl analog of 4a from 2-(phenylamino)benzoic acid 1-methylhydrazide ( 10 ) and triethyl orthoaeetate led only to the Schiff base intermediate, 2-(phenylamino)benzoic acid 2-(1-ethoxyethylidene)-1-methylhydrazide ( 11 ). Cyclization of 11 was attempted unsuccessfully with a variety of reagents. The intere?ting reaction products from the treatment of 11 with trifluoroacetic acid are described.     

1,4-Diacyl-3-acylamino-5-aryl-4,5-dihydro-1H-1,2,4-triazoles: Ring closure products of aromatic carbaldehyde (diaminomethylene) hydrazones with acylating agents

Summary Treatment of aromatic carbaldehyde (diaminomethylene)hydrazones1 with hot acetic anhydride or benzoyl chloride affords 1,4-diacyl-3-acylamino-5-aryl-4,5-dihydro-1H-1,2,4-triazoles2. In contrast, a new type of 0,N-acetal with an 1,2,4-triazole substructure (3) is obtained from 4-pyridine-carbaldehyde (diaminomethylene)hydrazone (li) by using a similar reaction procedure. The structures of all novel compounds were confirmed by spectroscopic data (¹H and¹³C NMR, MS, IR); some representative compounds were also studied by X-ray analysis.Dedicated to Professor Dr.S. Makleit on the occasion of his 65^th birthday.