2-Azido-1,3,4-thiadiazoles, 2-Azido-1,3-thiazoles,and Aryl Azides in the Synthesis of 1,2,3-Triazole-4-carboxylic Acids and Their Derivatives

Diazotization of 2-amino-1,3,4-thiadiazoles gave 1,3,4-thiadiazole-2-diazonium sulfates which were converted to 2-azido-1,3,4-thiadiazoles. The latter reacted with ethyl acetoacetate in the presence of sodium methoxide in methanol to produce 1-(5-R¹-1,3,4-thiadiazol-2-yl)-5-R²-1H-1,2,3-triazole-4-carboxylic acid derivatives. The reactions of 2-azido-5-methyl-1,3,4-thiadiazole and 2-azido-1,3-thiazole with ethyl 3-(1,3-benzodioxol-5-yl)-3-oxopropanoate led to the formation of 1,2,3-triazole ring under milder conditions (K₂CO₃, DMSO). Various 1,2,3-triazole-4-carboxylic acid derivatives were synthesized.     

Synthesis and properties of 5-amino-1,2,3-thiadiazole-4-carbothioamides

5-Amino-1,2,3-thiadiazole-4NR-carboxamides were reacted with P₄S₁₀, and 5-NR-amino-1,2,3-thiadiazole-4-carbonitriles with-H₂S. The reversible rearrangement of 5-amino-1,2,3-thiadiazole-4-NR-carbothioamides to 5-NR-amino-1,2,3-thiadiazole-4-carbothioamides was discovered.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1269–1273, September, 1988.     

Synthesis of novel 1,2,3-thiadizoles and 1,2,3-selenadiazoles as new antimicrobial agents

Abstract

A series of novel 1,2,3-thiadiazoles and 1,2,3-selenadiazoles having a long alkyl chain were synthesized by reacting semicarbazones with SOCl₂ and SeO₂, respectively. The structures of the target compounds 5–12 were confirmed by spectroscopy (IR, ¹H NMR, ¹³C NMR, and MS) and elemental analysis. Their antibacterial and antifungal activities were evaluated against six bacteria (Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis, Staphylococcus epidermidis, Staphylococcus aureus) and three fungi (Candida albicans, Candida parapsilosis, Candida tropicalis). The results of bioassays indicated that the compounds 5-Dodecyl-4-(4-methoxy-phenyl)-[1-3]selenadiazole (7), 4-Methyl-5-tetradecyl-[1-3]selenadiazole (8) and 5-Dodecyl-4-(4-methoxy-phenyl)-[1-3]thiadiazole (11) displayed moderate antibacterial activity against S. Epidermidis. On the other hand, according to antifungal screening results, compounds 5-Dodecyl-4-phenyl-[1-3]selenadiazole (5), 4-p-Tolyl-5-undecyl-[1-3]selenadiazole (6), and 5-Dodecyl-4-(4-methoxy-phenyl)-[1-3]selenadiazole (7) exhibited significant antifungal activities studied yeast strains.     

Syntheses and properties of H-1,2,3-triazoles

About twenty new H-1,2,3-triazoles (T) were readily synthesized by nucleophilic attack of sodium azide on activated acetylenes in dimethylformamide. Typical activating groups were COR, COOR, O₂NC₆H₄ PO(OC₂H₅, COT, and (C₆H₅)₃P⁺. Propynyl 4-triazolyl ketone or phenylethynyl 4-triazolyl ketone may be converted to acylic adducts (triazolylketoenamines), biheteroaromatic systems (isoxazolytriazoles, pyrazolytriazoles), as well as to ditriazolyl ketones. Certain T properties were examined in detail. The apparent pK′s for our group of ca 30 triazoles were in the range 4·95?9·45 in ethanol-water (v/v 1/1) at 25°. The Hammett correlation for five 4-aryl-T was log K_a = 0·89σ^? ?9·21 and for seven 4-aryl-5-carbethoxy-T was log K_a = 1·45σ?6·95. The UV spectra of T are similar to those of other heteroaromatic and phenyl compounds: interesting analogies between triazolyl and phenyl, e.g., ”ortho“ crowding effects, appear to be indicated in the spectra of compounds related to biphenyl, stilhene and benzophenone. With regard to structure assignment on the basis of spectra, characteristic features of UV and IR spectra of the H-1,2,3-triazoles are discussed.     

N-Alkylation of 4-nitro-1,2,3-triazole revisited. Detection and characterization of the N3-ethylation product, 1-ethyl-5-nitro-1,2,3-triazole

The products of the alkylation of sodium 4-nitro-1,2,3-triazolate with ethyl bromide were investigated using ¹H, ¹³C, and ¹⁵N NMR spectroscopy. It was found that alkylation proceeds on the triazole nitrogen atoms giving a mixture of three isomeric N-ethyl-4-nitro-1,2,3-triazoles. The molar ratio of N1, N2, and N3-alkylation products was 4:8:1. The formation of a minor N3-isomer, namely 1-ethyl-5-nitro-1,2,3-triazole was confirmed by X-ray structural analysis of single crystals of its tetranuclear copper(II) complex obtained by reaction of copper(II) chloride dihydrate with a mixture of the N2 and N3-isomers.     

Synthesis of 1,2,3,4-tetrazine 1,3-dioxides annulated with 1,2,3-triazoles and 1,2,3-triazole 1-oxides

1,2,3,4-Tetrazine 1,3-dioxides annulated with 1,2,3-triazoles and 1,2,3-triazole 1-oxides have been synthesized by the reaction of 4-amino-5-(tert-butyl-NNO-azoxy)-2-R-2H-1,2,3-triazoles (R=Me, i-Pr, t-Bu) and their 1-oxides (R=H, Me, Et, i-Pr) with the HNO₃/H₂SO₄/Ac₂O system. Their thermal stability, spectroscopic, and X-ray properties have been studied.     

Mass-spectrometric study of isomeric 5-amino-1,2,3-thiadiazoles and 5-mercapto-1,2,3-triazoles

The behavior of the isomeric 5-amino-1,2,3-thiadiazoles and 5-mercapto-1,2,3-triazoles under electron impact was studied. It was shown that mass spectrometry can serve as a rapid and reliable method for the identification of these compounds. Key factors in the assignment of a compound to one or the other class are the peaks of the [M-N₂]⁺ ions, which are more intense in the case of the thiadiazoles, and the ions determined by the decomposition of the prototropic forms of the triazoles. The compositions of the ions were determined by the high-resolution mass spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 681–689, May, 1987.     

[1,2,3]Triazoloazine/(Diazomethyl)azine Valence Tautomers from 5-Azinyltetrazoles

[1,2,3]Triazoloazines are formed by thermolysis of 5-azinyltetrazoles in the gasphase or in solution. Thus, 5-(2-pyridyl)tetrazole ( 7 ) and 5-(2-pyrazinyl)tetrazole ( 11 ) yield [1,2,3]triazolo[1,5-a]pyridine ( 9 ) and [1,2,3]triazolo[1,5-a]pyrazine ( 13 ), respectively, at 400°/10^?3 - 10^?5 Torr. 5-(2-Phenyl-4-quinazolinyl)tetrazole ( 15 ) gives 5-phenyl[1,2,3]triazolo[1,5-c]quinazoline ( 17 ) in 75% yield by heating under reflux in mesitylene solution. 2-(Diazomethyl)pyridine ( 8 ), a valence tautomer of 9 , can be trapped by fumaronitrile, leading to 3-(2-pyridyl)-1, 2-cyclopropanedicarbonitrile ( 19 ). The [1,2,3]triazoloazines undergo base catalysed H/D-exchange in D₂O solution.     

Crystal Structure and Solid-State Packing of 4-Chloro-5H-1,2,3-dithiazol-5-one and 4-Chloro-5H-1,2,3-dithiazole-5-thione

The crystal structure and solid-state packing of 4-chloro-5H-1,2,3-dithiazol-5-one and two polymorphs of 4-chloro-5H-1,2,3-dithiazole-5-thione were analyzed and compared to structural data of similar systems. These five-membered S,N-rich heterocycles are planar with considerable bond localization. All three structures demonstrate tight solid-state packing without voids which is attributed to a rich network of short intermolecular electrostatic contacts. These include S^δ+…N^δ−, S^δ+…O^δ−, S^δ+…Cl^δ− and S^δ+…S^δ− interactions that are well within the sum of their van der Waals radii (∑_VDW). B3LYP, BLYP, M06, mPW1PW, PBE and MP2 were employed to calculate their intramolecular geometrical parameters, the Fukui condensed functions to probe their reactivity, the bond order, Bird Index and NICS(1) to establish their aromaticity.     

SYNTHESIS AND STRUCTURE OF Pd(II) COMPLEXES OF 1,2,3-TRIPHENYLGUANIDINE

Abstract

The formation of two complexes by reaction of [PdCl₄]^2- with 1,2,3-triphenylguanidine (PhNH)₂C=NPh under different metal/ligand ratios has been observed and the structure of the complex [(1,2,3-triphenylguanidine)₂PdCl₂] has been determined by X-ray diffraction methods. The ligands are coordinated as neutral monodentate molecules to the metal centre through their imine nitrogen atoms. The second Pd(II) complex is [Pd(1,2,3-triphenylguanidine)₄]²⁺ and was isolated by precipitation with ClO^? ₄.     

Design,synthesis, and anticancer activity evaluation of novel aziridine-1,2,3-triazole hybrid derivatives

Some new 1-aryl-4-[(aziridine-1-yl)diaryl-methyl]-5-methyl-1H-1,2,3-triazole derivatives 7j–s were synthesized by the one-pot reaction of diaryl-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)methanol compounds 6j–s formed from 1-aryl-5-methyl-1H-1,2,3-triazole-4-carboxylic acid derivatives. The new compounds 7j–s and 6j–s are investigated by ¹H and ¹³C NMR, MS, and IR. The anticancer activity of the synthesis target compounds was evaluated against human leukemia (HL-60) cells and human hepatoma G2 cells. Some of the compounds were highly efficient. The ¹H-NMR signals of the aziridine-ring cis-H/trans-H protons were found to be two group peaks at 1.800–1.884 and 1.183–1.327?ppm.     

2-Alkyl-4-amino-5-(tert-butyl-NNO-azoxy)-2H-1,2,3-triazole 1-oxides: synthesis and reduction

A new approach to the synthesis of 4-amino-5-(tert-butyl-NNO-azoxy)-2-R-2H-1,2,3-triazole 1-oxides 1 was developed. Compounds 1 were obtained by reactions of 3-amino-4-(tert-butyl-NNO-azoxy)furoxan with aliphatic amines RNH₂ (R = Me, Et, Prⁱ, Bu, and Bu^t). 4-Amino-5-(tert-butyl-NNO-azoxy)-2-tert-butyl-2H-1,2,3-triazole 1-oxide was transformed under the action of acids into 4-amino-5-(tert-butyl-NNO-azoxy)-1-hydroxy-1H-1,2,3-triazole. Methylation of the latter with diazomethane mainly involves the O atom of the triazole oxide ring. Reduction of compounds 1 gave 4-amino-5-(tert-butyl-NNO-azoxy)-2-R-2H-1,2,3-triazoles and 4-amino-5-(tert-butyldiazenyl)-2-R-2H-1,2,3-triazoles (R = Me, Prⁱ, and Bu^t). The structures of the compounds obtained were confirmed by ¹H, ¹³C, and ¹⁴N NMR spectroscopy.     

Copper(II), nickel(II) and cobalt(II) complexes of 5,5-dimethylcyclohexane-1,2,3-trione-2-arylhydrazones

Summary Copper(II), nickel(II) and cobalt(II) perchlorate complexes of 5,5-dimethylcyclohexane-1,2,3-trione-2-(p-nitrophenyl-hydrazone) (HL¹), 5,5-dimethyl-cyclohexane-1,2,3-trione-2-(p-chlorophenylhydrazone) (HL²), 5,5-dimethylcyclohexane-1,2,3-trione-2-(o-chlorophenylhydrazone) (HL⁴), 5,5-dimethylcyclohexane-1,2,3-trione-2-(o-methylphenyl-hydrazone) (HL⁵) and 5,5-dimethylcyclohexane-1,2,3-trione-2-(m-methylphenylhydrazone) (HL⁶) have been prepared, and characterized using analytical, spectral and magnetic measurements. The data reveal that the reaction of Cu(ClO₄)₂ (1 mol) in EtOH, with all ligands, produces complexes of the type CuL(ClO₄)(H₂O).nH₂O. Nickel(II) and cobalt(II) perchlorates react only with HL¹ and HL² to produce the complexes ML(ClO₄)(H₂O)₃ (where M = Ni^II, L = L^– and L², M = Co^II, L = L¹) and Co(HL₂)₂-(ClO₄)₂.2H₂O. The spectral data show that the ligands behave as monobasic bidentate in their azo forms, except HL² which reacts with cobalt(II) as a neutral bidentate ligand in its hydrazone form.     

4,5-dihydro-6h-pyrrolo[1,2,3-d,e]quinoxalin-5-ones

The synthesis of 1-R¹-2-R²-8-R³-4,5-dihydro-6H-pyrrolo[1,2,3-d,e]quinoxalin-5-one derivatives (where R¹ = CH₃, C₂H₅; R² = CH₃, COOC₂H₅; R³ = H, CH₃, C₂H₅O, Cl, Br) is described. The physicochemical properties of these derivatives were also studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 839–841, June, 1979.     

Reactions of 1,2,3-Triazoles with Trifluoromethanesulfonyl Chloride and Trifluoromethanesulfonic Anhydride

Reactions of 4,5-dibromo-1,2,3-triazole, 1H-1,2,3-benzotriazole, and 2-phenyl-2H-1,2,3-triazole-4-carbonyl chloride with trifluoromethanesulfonyl chloride and trifluoromethanesulfonic anhydride were studied. 4,5-Dibromo-1,2,3-triazole sodium salt reacted with CF₃SO₂Cl in tetrahydrofuran to give 4,5-dibromo-2-(2-tetrahydrofuryl)-2H-1,2,3-triazole rather than expected 4,5-dibromo-2-trifluoromethylsulfonyl-2H-1,2,3-triazole. The latter was synthesized by treatment of 4,5-dibromo-1,2,3-triazole sodium salt with trifluoromethanesulfonic anhydride. The reaction of benzotriazole with (CF₃SO₂)₂O afforded 1-trifluoromethylsulfonyl-1H-1,2,3-benzotriazole and 1,2,3-benzotriazolium trifluoromethanesulfonate. 2-Phenyl-2H-1,2,3-triazole-4-carbonyl chloride reacted with trifluoromethanesulfonamide sodium salt in DMF, yielding N-(dimethylaminomethylene)trifluoromethanesulfonamide. Possible ways for formation of the unexpected products were proposed.     

Synthesis of aryl-functionalized, 1,5-disubstituted 1,2,3-triazoles and derivatives by arylation of zwitterionic ruthenium triazolato complexes

The synthesis of a series of ruthenium 1,5-disubstituted 1,2,3-triazolato complexes, 1,5-disubstituted 1,2,3-triazoles, and a triazolium salt is reported. Treatment of the ruthenium azido complex [Ru]-N₃ ( 1 , [Ru] = (η⁵-C₅H₅)(dppe)Ru, dppe = Ph₂PCH₂CH₂PPh₂) with an excess of ethyl propiolate results in the formation of a mixture of the Z- and E-forms of zwitterionic N(1)-bound N(3)-ethyl acryl-4-carboxylate triazolato complexes [Ru]N₃(CH=CHCO₂Et)C₂H(CO₂) ( Z - 2 ) and ( E - 2 ). The arylation of 2 with aromatic bromides gives a series of cationic N(1)-bound N(3)-ethyl acryl-4-alkoxycarbonyl triazolato complexes {[Ru]N₃(CH=CHCO₂Et)C₂H(CO₂CH₂R)}[Br] ( 3a , R = Ph ; 3b , R = C₆F₅; 3c , R = 4-C₆H₄CN, 3d , R = 2,6-C₆H₃F₂) and the subsequent cleavage of the Ru-N bond of 3a–d gives 1,5-disubstituted 1,2,3-triazoles N₃(CH=CHCO₂Et)C₂H(CO₂CH₂R) ( 4a , R = Ph; 4b , R = C₆F₅; 4c , R = 4-C₆H₄CN; 4d , R = 2,6-C₆H₃F₂) and [Ru]-Br. A 1,2,3-triazolium salt [N₃(CH=CHCO₂Et)(CH₂C₆F₅)C₂H₂][Br] ( 5 ) was formed by transformation of 4b in BrCH₂C₆F₅/chloroform mixture. The structures of Z-3a and Z-5 were confirmed by single-crystal x-ray diffraction analysis and both complexes participate in non-covalent aromatic interactions in the solid-state structures which can be favorable in the binding of DNA/biomolecular targets and have shown great potential in the application of biologically active anticancer drugs.     

Synthesis and properties of 4-substituted 5H-1,2,3-dithiazol-5-ylidenes

Substituted ethanone oximes react with S₂Cl₂ and pyridine to give 1,2,3-dithiazolium chlorides. The treatment of these products with malonodinitrile in dichloromethane affords 4-substituted 5 H-1,2,3-dithiazol-5-ylidenes. The reaction of the latter compounds with n-butylamine unexpectedly yielded addition products at one of the nitrile groups, viz. substituted 1,2,3-dithiazol-5-ylideneethanimidamides.     

2,2-Difluor-1,2,3-trimethyl-1,3-diaza-2λ5-phospholidin

2,2-Difluoro-1,2,3-trimethyl-1,3-diaza-2λ⁵-phospholidine The title compound 1 is obtained in about 50% yield by oxidative fluorination of 1,2,3-trimethyl-1,3-diaza-2λ³-phospholidine, 6 , with IF₅. 1 is characterized by its nmr, mass, and ir spectra.     

Alkylation of 1,2,3-benzotriazole with iodomethyl ketones

Solvent-free reactions of 1,2,3-benzotriazole with 1-iodopropan-2-one and 1,3-diiodopropan-2-one in the absence of a catalyst involved alkylation of the heteroring at the N¹ atom and subsequent quaternization at the N³ atom with formation of 1,3-bis(2-oxopropyl)-1H-1,2,3-benzotriazolium triiodide which is a new conducting ionic liquid. The reaction of 1,2,3-benzotriazole with 1,3-diiodopropan-2-one was accompanied by reductive deiodination of the iodomethyl groups in the initial ketone with hydrogen iodide liberated by N¹-alkylation. Triiodide ion readily exchanges for nitrate ion by the action of AgNO₃ to produce 1,3-bis(2-oxopropyl)-1H-1,2,3-benzotriazolium nitrate. The reaction of 1,2,3-benzotriazole with 2-iodo-1-phenylethan-1-one in melt resulted in the formation of 1,3-bis(2-oxo-2-phenylethyl)-1H-1,2,3-benzotriazolium triiodide.     

Mass spectra of 4,5-disubstituted 1,2,3-thiadiazoles

The schemes of the fragmentation of 4-substituted 5-arylamino-1,2,3-thiadiazoles were established on the basis of electron-impact mass spectra and high-resolution mass-spectrometric data, and the effect of substituents on the fragmentation pathways was analyzed. It is shown that the cyclization of the [M-N₂]⁺ ions formed in the fragmentation of compounds that contain a thiocarboxamido group in the 4 position proceeds with the participation of the most nucleophilic heteroatom.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 118–122, January, 1988.