Synthesis of novel dendrimers containing pyrimidine units

A novel convergent approach to dendritic macromolecules is described in which 4,6-dichloro-2-(4-methoxyphenyl)-pyrimidine is used as the building block. The nucleophilic aromatic substitution reaction at this AB₂-monomer was used as the key step in the propagation of the dendrons. Different core reagents were used to form the dendrimers, including a 5,15-bis(pyrimidyl)porphyrin core. Fourth-generation dendrons and third-generation dendrimers could be synthesized. The presented dendrimers are promising candidates to be used in applications where a more rigid structure and a larger resistance towards the applied conditions is required.     

Air-oxidized products of multi-component reactions between 3-amino-1,2,4-triazole, aromatic aldehydes and isonitriles

The Groebke-type multi-component reaction (MCR) between 3-amino-1,2,4-triazole, aromatic aldehydes and isonitriles has been studied from the viewpoint of convenient generation of combinatorial arrays of imidazo[1,2-b][1,2,4]triazoles. However, it was established that the desired heterocyclic structures can be produced in moderate to good yields in an oxidized form, when benzylic isonitriles are used. Oxidation occurred at the benzylic position to produce N-alkylidene-4H-imidazo[1,2-b][1,2,4]triazol-6-amines that proved to be unusually stable towards acid hydrolysis and reduction. The presence of an easily oxidized benzylic position in the target structures is thought to be the prerequisite for successful Groebke-type MCR of 3-amino-1,2,4-triazole.     

微波促进下3-(2-苯并呋喃基)-4-氨基-5-巯基-1,2,4-三唑

微波辐射条件下, 首先由2-苯并呋喃甲酰肼依次与二硫化碳和水合肼反应合成3-(2-苯并呋喃基)-4-氨基-5-巯基- 1,2,4-三唑, 进一步在微波辐射条件下由4-氨基-5-巯基-1,2,4-三唑分别与芳甲酸/芳氧基乙酸、α-溴代苯乙酮及芳醛反应以较高产率制得了相应的1,2,4-三唑并[3,4-b]-1,3,4-噻二唑、1,2,4-三唑并[3,4-b]-1,3,4-噻二嗪及4-芳亚甲基亚胺基-5-巯基-1,2,4-三唑. 产物结构经IR, ¹H NMR, MS及元素分析进行了表征.     

α-Oxides in reactions with N-H acids of the heterocyclic series

The reaction of epoxides with 3-nitro-5-bromo-1,2,4-triazole gave a series of 1-(β-hydroxyalkyl)-3-nitro-5-bromo-1,2,4-triazoles, which, under the influence of bases, undergo intramolecular cyclization with HBr elimination to give an ew heterocyclic system — 2-nitro-5,6-dihydrooxazolo[2,3-e]-1,2,4-triazole.     

Arylidene Polymers. XVII. Cyclization of Aromatic Poly[dibenzylidenecyclopentanone-Hydrazide] as a Route to Polyheterocyclic 1,3,4-Oxadiazole and 1,2,4-Triazole

A new interesting class of thermal stable arylidene polymers containing 1,3,4-oxadiazole and 1,2,4-triazole moieties in the main chain have been synthesized from aromatic polyhydrazide I. Cyclization of I at 250°C in the absence of solvent was found to be the best pathway for the inclusion of the 1,3,4-oxadiazole moiety in the main chain. Heating of I with aniline, cyclohexyl amine, or 3-amino pyridine at 180°C for 30 h gave the corresponding 1,2,4-triazole polymers III. The introducing effect of different aromatic, cycloalkyl, and heterocyclic amines in III_a-c and IV_a-c on thermal stability behavior was studied by TGA analysis. Moreover, all the polymers were characterized by elemental and spectral analyses, solubility, and viscometry measurements. X-ray diffractograms of the synthesized polymers showed they had less crystallinity than the polyhydrazide precursors.     

First cross-coupling reactions on halogenated 1H-1,2,4-triazole nucleosides

The halogenated 1H-1,2,4-triazole glycosides 6-10 were synthesized by BF₃-activated glycosylation of 3(5)-chloro-1,2,4-triazole (2), 3,5-dichloro-1,2,4-triazole (3), 3,5-dibromo-1,2,4-triazole (4), and 3(5)-bromo-5(3)-chloro-1,2,4-triazole (5) with 1,2,3,4-tetra-O-pivaloyl-β-d-xylopyranose (1). The β-anomeric major products 3-chloro-1-(2,3,4-tri-O-pivaloyl-β-d-xylopyranosyl)-1,2,4-triazole (6β), 3,5-dichloro-1-(2,3,4-tri-O-pivaloyl-β-d-xylopyranosyl)-1,2,4-triazole (7β), and 3,5-dibromo-1-(2,3,4-tri-O-pivaloyl-β-d-xylopyranosyl)-1,2,4-triazole (8β) were used as starting materials for transition metal catalyzed C-C-coupling reactions. Arylations of the triazole ring of 7β, and 8β were successful in 5-position with phenylboronic acid, 4-vinylphenylboronic acid, and 4-methoxyphenylboronic acid, respectively, under Suzuki cross-coupling conditions (products 11-17). Moreover, a Cu-catalyzed perfluoroalkylation of 8β is reported with 1-iodo-perfluorohexane yielding 3-perfluorohexyl-1-(2,3,4-tri-O-pivaloyl-β-d-xylopyranosyl)-1,2,4-triazole (18). Compound 18 was depivaloylated to the trihydroxy derivative 19. The copper-mediated reaction of 8β with Rupert's reagent gave the bis(3-bromo-1-(2,3,4-tri-O-pivaloyl-β-d-xylopyranosyl)-1,2,4-triazol-5-yl) (20).     

Photochemical reactions of group VIB metal carbonyls with heterocyclic Schiff bases derived from 4-amino -3-hydrazino-5-mercapto-1,2,4-triazole

The new complexes, M(CO)₅(Schiff base) [M?=?Cr; 1, Mo; 2, W; 3, Schiff base?=?4-salicylidenamino-3-hydrazino-5-mercapto-1,2,4-triazole, SAHMT, a; 4-(2-hydroxynaphthylidenamino)-3-hydrazino-5-mercapto-1,2,4-triazole, 2HNAHMT, b; 4-(3-hydroxybenzylidenamino)-3-hydrazino-5-mercapto-1,2,4- triazole, 3HBAHMT, c; 4-(4-hydroxybenzylidenamino)-3-hydrazino-5-mercapto-1,2,4- triazole, 4HBAHMT, d; 4-(5-bromosalicylidenamino)-3-hydrazino-5-mercapto-1,2,4-triazole, 5BrSAHMT, e; were synthesized by photochemical reaction of metal carbonyls M(CO)₆ (M?=?Cr, Mo, W) with new heterocyclic Schiff bases derived from 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole, a–e. The ligands and complexes have been characterized by elemental analysis, EI-mass spectrometry, FT-IR, ¹H and ¹³C-{¹H}-NMR spectroscopy. The spectroscopic studies show that Schiff bases, a–e, are monodentate and coordinate via azomethine N donor to the central metal atom in M(CO)₅(Schiff base) (M?=?Cr, Mo, W).     

Synthesis of fused 3-amino-1,2,4-triazoles via sequential addition of aryl hydrazines to isothiocyanates and I2-mediated cyclodesulfurization

A variety of fused 3-amino-1,2,4-triazole derivatives were synthesized via addition of aryl hydrazines to isothiocyanates followed by I₂-mediated oxidative cyclodesulfurization. This transition-metal-free synthetic process provides facile access to 1,2,4-triazolo[4,3-a]pyridines and related heterocyclic frameworks bearing a 3-amino substituent from readily accessible substrates in an efficient and scalable fashion.     

AB3 building blocks for the synthesis of polyester dendrimers

Syntheses of several examples of a new type of trivalent building blocks for the preparation of aliphatic polyester dendrimers are presented. Starting from the well-known mono-O-benzylidenepentaerythritol, AB₃ type acid dendrons can be obtained in high yield in only two steps. Other triprotected bis-2,2-(hydroxymethyl)-3-hydroxypropanoic acid derivatives with varying protecting groups were also synthesized readily. This type of dendron was used in combination with 2,2′-bis(hydroxymethyl) propanoic acid (bis-HMPA) divalent dendrons to produce low generation mixed polyester dendrimers with increased number of branching points.     

Synthesis and Antibacterial Activity of Novel 5,5′-(Pyridine-2,6-Diyl)bis(4-Arylideneamino-3-Mercapto-1,2,4-Triazole)-Related Derivatives

The reaction of 5,5′-(pyridine-2,6-diyl)bis(4-amino-3-mercapto-1,2,4-triazole) with various aromatic aldehydes in acetic acid yielded the corresponding 5,5′-(pyridine-2,6-diyl)bis(4-arylideneamino-3-mercapto-1,2,4-triazole) derivatives. The structures of the synthesized compounds as well as their intermediates were confirmed by elemental analysis, infrared spectra, ¹H NMR spectra and mass spectra studies. All the synthesized title compounds were screened for their antibacterial activities, and the preliminary results revealed that some of them showed good activities against Escherichia coli and Pseudomonas aeruginosa.     

Synthesis,characterization and biological activity of Hg(II), Fe(III) complexes with 1,3,4-oxadiazole, 1,2,4-triazole derivatives from L-methionine

Four novel heterocyclic1,3,4-oxadiazole, 1,2,4-triazole derivatives, namely: 5-[1-amino-3-(methylsulfanyl)propyl]-1,3,4-oxadiazole-2(3H)-thione (4), 4-amino-5-[1-amino-3-(methylsulfanyl)propyl]-4H-1,2,4-triazole-3-thiol (5), 1-amino-3-[1-amino-3-(methylsulfanyl)propyl]-1H-1,2,4-triazole-5-thiol (7), and 5-[1-amino-3-(methylsulfanyl)propyl]-1H-1,2,4-triazole-3-thiol (9) have been synthesized from l-methionine and characterized by different spectroscopic techniques (FT-IR, UV–Vis, ¹H NMR, ¹³C NMR and MS). Complex formation with Hg⁺⁺ and Fe⁺⁺⁺ ions were formed from the four heterocyclic 4, 5, 7 and 9. The antimicrobial activities for synthetic intermediates and final four products were assisted using paper disk diffusion method against Gram-negative bacteria: Escherichia coli, Pseudomonas aeroginosae and Gram-positive bacteria: Staphylococus aureus 25923, Staphylococus aureus 43300 and showed variant activity against some of the microorganisms tested.     

Regioselective alkylation of amino- and mercapto-1,2,4-triazoles with t-BuOH–HClO4

The behavior of amino- and mercapto-1,2,4-triazoles in a t-BuOH–HClO₄ system has been examined. Under the investigated conditions monoalkylation of 3-amino-1,2,4-triazole proceeds at the endocyclic N1 atoms whereas 1,2,4-triazole-3-thiol undergoes S-tert-butylation. Exhaustive alkylation of the above mentioned triazoles results in di-tert-butyl substituted derivatives, which give 1,3-disubstituted triazoles under the action of base. 4-Amino-1,2,4-triazole undergoes alkylation on the amino group as well as on the endocyclic N1 atom giving a 1,4-disubstituted triazolium salt. An X-ray diffraction investigation of 5-tert-butylsulfanyl-1,2,4-triazole, 1-tert-butyl-3-tert-butylamino-1,2,4-triazol-4-ium, 1-tert-butyl-3-tert-butylsulfanyl-1,2,4-triazol-4-ium, and 1-tert-butyl-4-tert-butylamino-1,2,4-triazolium perchlorates was carried out.     

Second-harmonic properties of dendritic polymers skeleton-constructed with azobenzene moiety used for nonlinear optical materials

A series of dendrons and dendrimers skeleton-constructed with azobenzene moiety were synthesized and doped in a high T_g polycarbonate (PC) as a host for nonlinear optical (NLO) materials. The optimal loading density and poling conditions were investigated using UV-vis spectral and second-harmonic generation (SHG) measurements. The results showed that the dendrons and dendrimers have good solubility in PC host, which increased with the generation increased. Moreover, the SHG measurements indicated that the dendrons possess higher nonlinearity than the dendrimers. The chromophores of lower generation dendrons were easier to orient along the poling electric field and gave a cone shape with the azobenzene branching units, which coherently contributed to the molecular hyperpolarizability and resulted in the higher SHG intensity. The temporal stability of the dendrons with 15% loading density was also investigated, and showed that the decaying in nonlinearity was slower for higher generation dendrons.     

Quantum chemical studies of azoles 3. Thermodynamic stabilities of neutral molecules and intermediates formed in electrophilic substitution of azoles containing three or four heteroatoms

Density functional theory quantum chemical calculations of thermodynamic stabilities in the gas phase and in water were carried out for 1,3,4-oxadiazole and 1,3,4-thiadiazole, 1,2,4-1H-triazole and 1,2,4-4H-triazole, 1,2,3,4-1H-tetrazole and 1,2,3,4-2H-tetrazole molecules, and for cationic and bipolar (carbenoid) intermediates formed by these molecules in electrophilic substitution reactions (with proton as model electrophile) and the results obtained are compared. Differences in the chemical behavior of pairs of isomeric 1H- and 4H-1,2,4-triazoles and 1H- and 2H-tetrazoles are analyzed.     

The first stable examples of compounds containing both diazonium and acyl azide,and synthesis of a new pyrazino[2′,3′:3,4]pyrazolo[5,1-c][1,2,4]triazin-4(6H)-one heterocyclic system

The first stable compound containing both N₂⁺BF₄^? and CON₃ functional groups – 8-azidocarbonyl-3-(tert-butyl)-4-oxo-4,6-dihydropyrazolo[5,1-c][1,2,4]triazine-7-diazonium tetrafluoroborate was synthesized, and its stability and reactivity discussed. The Curtius rearrangement of 7-azido-3-(tert-butyl)-4-oxo-4,6-dihydropyrazolo[5,1-c][1,2,4]triazine-8-carbonylazide was investigated, and the synthesis of a novel heterocyclic system –pyrazino[2′,3′:3,4]pyrazolo[5,1-c][1,2,4]triazin-4(6H)-one is described.     

Studies with polyfunctionally substituted heteroaromatics: 2-Phenyl-4-p-tolylhydrazono-2-oxazoline-5-one as a precursor for the synthesis of substituted 1,2,4-triazoles and pyridines

2-Phenyl-4-p-tolylhydrazono-2-oxazoline-5-one ( 3 ) was rearranged by the action of phenols and naphthols into 1,2,4-triazole-5-carboxylic esters ( 5 ) that were rearranged further on reflux in AcOH-ZnCl₂ into triazolyl ketones ( 7 ). Rearrangement of 3 into 1,2,4-triazole derivatives could also be effected by the action of heterocyclic amines and 1-naphthylamine. © John Wiley & Sons, Inc.     

Synthesis and Luminescent Properties of s-Tetrazine Derivatives Conjugated with the 4H-1,2,4-Triazole Ring

New derivatives obtained by the combination of unique 1,2,4,5-tetrazine and 4H-1,2,4-triazole rings have great application potential in many fields. Therefore, two synthetic few-step methodologies, which make use of commercially available 4-cyanobenzoic acid (method A) and ethyl diazoacetate (method B), were applied to produce two groups of the aforementioned heterocyclic conjugates. In both cases, the target compounds were obtained in various combinations, by introducing electron-donating or electron-withdrawing substituents into the terminal rings, together with aromatic or aliphatic substituents on the triazole nitrogen atom. Synthesis of such designed systems made it possible to analyze the influence of individual elements of the structure on the reaction course, as well as the absorption and emission properties. The structure of all products was confirmed by conventional spectroscopic methods, and their luminescent properties were also determined.     

Synthesis of Novel Biodegradable Cationic Dendrimers

Summary: Dendrons and dendrimers with cationic amino groups at their periphery were successfully synthesized up to the third and second generation, respectively. The results obtained by ¹H NMR spectroscopy and gel permeation chromatography analysis supported the formation of the targeted dendrons and dendrimers. The dendrons were grown via ester linkages, which endowed them with biodegradability in D₂O at 37 °C. The degradation rate depends upon the steric hindrance and reactivity caused by the bulkiness and compact structure of the dendrons. All of the synthesized dendrons were degraded within a month, while 60% of the ester groups in the sterically crowded dendrimers were degraded over the same time period. The cytotoxicity of the dendrons was evaluated by the MTT assay on a 293T cell line which indicated that the obtained dendrons were completely non‐toxic. These non‐toxic, biodegradable cationic dendrons and dendrimers are believed to have potential applications in the biomedical field.

Synthetic procedure of dendrons and dendrimers.     

Intramolecular hydrogen bonds C-H?N in bisheterocyclic compounds according to 1H and 13C NMR data

Data of ¹H and ¹³C NMR spectra show that in 2,2??-bipyridyl, 1-vinyl-2(2??-pyridyl)benzimidazole, 1-vinyl-3-vinylsulfanyl-5-(2-furyl)-1,2,4-triazole, and 1-vinyl-5-vinylsulfanyl-3-(2-furyl)-5-vinylthio-1,2,4-triazole exists a weak intramolecular hydrogen bond between the heterocyclic fragments. It causes a downfield shift of the bridging proton signal in the ¹H NMR spectrum by 0.6?C0.7 ppm and an increase in the corresponding direct coupling constant ¹³C-¹H by 1.5?C2.0 Hz. These variations in the spectral parameters can be efficiently used in the conformational analysis for establishing with the use of NMR method which conformers are predominantly populated in the heterocyclic compounds.     

Conversion of 4-amino-4H-1,2,4-triazole to 1,3-bis(1H-azol-l-yl)-2-aryl-2-propanols and 1-phenacyl-4-[(benzoyl or 4-toluenesulfonyl)-imino]-(1H-1,2,4-triazolium) Ylides

A series of 1,3-bis(1H-azol-1-yl)-2-aryl-2-propanols 17 were synthesized in an one-pot procedure by reacting l-aryl-2-(1H-1,2,4-triazol-l-yl)- or l-aryl-2-(1H-imidazol-l-yl)ethanones with dimethylsulfoxonium methide in the presence of either 1,2,4-triazole or imidazole. The aromatic groups in 17 were either 4-bromo-, 4-chloro-, 2,4-dichloro- or 2,4-difluorophenyl. 4-Amino-4H-1,2,4-triazole was acylated with either benzoyl or 4-toluene-sulfonyl chloride to afford [4-(benzoyl or 4-toluenesulfonyl)amino]4H-1,2,4-triazole. Subsequent alkylations with 4-bromo- or 4-chlorophenacyl bromide produced 1-(4-bromo- or 4-chlorophenacyl)-4-[(benzoyl- or 4-toluenesulfonyl)amino]-1H-1,2,4-triazolium bromides. Neutralizations of these salts provided the corresponding ylides.