Excess Of Hydrazine Hydrate Research Articles

Synthesis, biochemical and computational evaluations of novel bis-acylhydrazones of 2,2′-(1,1′-biphenyl)-4,4′-diylbis(oxy))di(acetohydrazide) as dual cholinesterase inhibitors

A series of twenty-seven bis(acylhydrazones) were successfully synthesized with high yields through a multistep process, which entailed the esterification of hydroxyl groups, hydrazination with an excess of hydrazine hydrate, and subsequent reactions with various carbonyl moieties (aldehydes). In the final stage of synthesis, different chemical species including aromatic, heterocyclic, and aliphatic compounds were integrated into the framework. The resulting compounds were characterized using several spectroscopic techniques (1H NMR, 13C NMR, and mass spectrometry). Their anticholinesterase activities were assessed in vitro by examining their interactions with two cholinesterase enzymes: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among the synthesized hits, compounds 3, 5, 6, 9–12, and 14 exhibited good to moderate inhibition of AChE. Specifically, 10 (IC50 = 26.3 ± 0.4 μM) and 11 (IC50 = 28.4 ± 0.5 μM) showed good inhibitory activity against AChE, while 9, 12, 3, and 6 exhibited significant inhibition potential against AChE with IC50 values ranging from 35.2 ± 1.1 μM to 64.4 ± 0.3 μM. On the other hand, 5 (IC50 = 22.0 ± 1.1 μM) and 27 (IC50 = 31.3 ± 1.3 μM) displayed significant, and 19 (IC50 = 92.6 ± 0.4 μM) showed moderate inhibitory potential for BChE. Notably, 5 and 27 exhibited dual inhibition of AChE and BChE, with greater potency than the standard drug galantamine. The binding patterns of these molecules within the binding cavities of AChE and BChE were anticipated by molecular docking which showed good correlation with our in vitro findings. Further structural optimization of these molecules may yield more potent AChE and BChE inhibitors.

Design and Synthesis of Novel Bis Thiazolo[4,5-c]Isoxazolines Bearing 1,2,4-triazole Ring Derived From the Related 4-thiazolidinons as Antimicrobial Agents

Design and synthesis of novel poly heterocycles together using same heterocyclic compound is the main task of the present paper. The target compounds entitled 4,4’-[benzene-1,4-diylbis[ethylidenehydrazine-2-ylidene]bis[4-[3,5-di(5-substitutedpyridin-2-yl)-3,3a-dihydro[1,3]thiazolo[4,5-c][1,2]oxazol-6(5H)-yl]-4H-3-yl-1,2,4-triazole-3-thiol] have been synthesized starting from the reaction of 1,4-diacetylphenyl and carbohydrazide to give Schiff base derivatives then 1,2,4- triazole derivatives from the reaction with CS2 and an excess of hydrazine hydrate. The same applies for the condensing of these newly heterocyclic amines with different pyridine-2-carbaldehydes, which resulted in the synthesis of some new Schiff bases, which were then cyclized to develop new thiazolidinones by thioglycolic acid. Additionally, by fusing thiazolidinones with various pyridine-2-carbaldehydes, a novel chalcone was formed. To produce the desired fused isoxazolines, the later compounds underwent cyclization with hydroxylamine hydrochloride and potassium hydroxide. From the examination of the (CHN), FTIR, 1H NMR, and 13C NMR spectra, the structural identities of all recently synthesized compounds were determined. The newly synthesized chemicals were also successfully tested as an antibacterial agent.

Synthesis, molecular structure and urease inhibitory activity of novel bis-Schiff bases of benzyl phenyl ketone: A combined theoretical and experimental approach

BackgroundUrease belongs to the family of amid hydrolases with two nickel atoms in their core structure. On the basis of literature survey, this research work is mainly focused on the study of bis-Schiff base derivatives of benzyl phenyl ketone nucleus. ObjectiveSynthesis of benzyl phenyl ketone based bis-Schiff bases in search of potent urease inhibitors. MethodIn the current work, bis-Schiff bases were synthesized through two steps reaction by reacting benzyl phenyl ketone with excess of hydrazine hydrate in ethanol solvent in the first step to get the desired hydrazone. In last, different substituted aromatic aldehydes were refluxed in catalytic amount of acetic acid with the desired hydrazone to obtain bis-Schiff base derivatives in tremendous yields. Using various spectroscopic techniques including FTIR, HR-ESI-MS, and 1H NMR spectroscopy were used to clarify the structures of the created bis-Schiff base derivatives. ResultsThe prepared compounds were finally screened for their in-vitro urease inhibition activity. All the synthesized derivatives (3–9) showed excellent to less inhibitory activity when compared with standard thiourea (IC50 = 21.15 ± 0.32 µM). Compounds 3 (IC50 = 22.21 ± 0.42 µM), 4 (IC50 = 26.11 ± 0.22 µM) and 6 (IC50 = 28.11 ± 0.22 µM) were found the most active urease inhibitors near to standard thiourea among the synthesized series. Similarly, compound 5 having IC50 value of 34.32 ± 0.65 µM showed significant inhibitory activity against urease enzyme. Furthermore, three compounds 7, 8, and 9 exhibited less activity with IC50 values of 45.91 ± 0.14, 47.91 ± 0.14, and 48.33 ± 0.72 µM respectively. DFT used to calculate frontier molecular orbitals including; HOMO and LUMO to indicate the charge transfer from molecule to biological transfer, and MEP map to indicate the chemically reactive zone suitable for drug action. The electron localization function (ELF), non-bonding orbitals, AIM charges are also calculated. The docking study contributed to the analysis of urease protein binding.

Modulating the Electronic Structure of α-Fe2O3 by Doping Atomically Dispersed Ce for the Transfer Hydrogenation of Nitroaromatics Using Stoichiometric Hydrazine Hydrate

The metal-oxide-catalyzed transfer hydrogenation of nitroarenes to anilines by hydrazine hydrate has been widely reported; however, the risk of explosion resulting from excess hydrazine hydrate and high temperatures and complex preparations of these catalysts immensely hinder their industrial application. Herein, we use a simple co-precipitation method to synthesize atomically dispersed Ce-doped α-Fe2O3 (Ce0.025-Fe2O3-350 °C), which can completely reduce nitroarenes using stoichiometric hydrazine hydrate at room temperature, where the parent α-Fe2O3 is inactive. A thorough characterization indicates that the incorporation of Ce into the crystal lattice of α-Fe2O3 reorganizes the electronic structure of the surrounding Fe, such that the Lewis acidity of Fe2O3 is enhanced, which is the key for the room-temperature decomposition of N2H4·H2O. The structure is also beneficial for the adsorption of nitroarene, leading to the weakening of the N–O bonds. Mechanistic experiments and DFT calculations demonstrate that the reduction proceeds through Ph-NO2 → Ph-NHOH → Ph-NH2 without the widely recognized Ph-NO intermediate. Moreover, Ce0.025-Fe2O3-350 °C exhibits good stability in a continuous-flow reaction.

New supramolecules of bis(acylhydrazones)-linked bisphenol sulfide for Alzheimer's: targeting cholinesterases by in vitro and in silico approaches.

In current research, two functional components, i.e., hydrazone and bisphenol sulfide were combined to get useful supramolecules in medicinal chemistry. Herein 25 new 4,4'-thiodiphenol bis-acylhydrazones were synthesized in good to excellent yields. Initially ethyl-2-chloroacetate was reacted with 4,4'-thiodiphenol, which was further reacted with excess hydrazine hydrate to produce 2,2'-((thiobis(4,1-phenylene))bis(oxy))di(acetohydrazide), which was then combined with various aromatic and aliphatic aldehydes to get the desired products (hydrazones, 4a-4y). The synthesized supramolecules were characterized by contemporary spectroscopic techniques such as 1H NMR, 13C NMR, and mass spectroscopy. The synthetic compound's cholinesterase blocking activity was tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes where compounds 4n, and 4h showed excellent inhibitory potential for AChE, while 4b, and 4h, demonstrated most potent inhibition of BChE. The starting compound (SM3) and compounds 4h and SM3 depicted excellent dual inhibitory capabilities for both enzymes. The chemical basis of anticholinesterase activity was investigated using a structure-based molecular docking approach. The biological significance and the ease of synthesis of this class of compounds should be considered in therapeutic development for Alzheimer's disease treatments.

Room-Temperature Ferromagnetism in Perylene Diimide Organic Semiconductor.

The development of pure organic magnets with high Curie temperatures remains a challenging task in material science. Introducing high-density free radicals to strongly interacting organic molecules may be an effective method to this end. In this study, a solvothermal approach with excess hydrazine hydrate is used to concurrently reduce and dissolve rigid-backbone perylene diimide (PDI) crystallites into the soluble dianion species with a remarkably high reduction potential. The as-prepared PDI powders comprising radical anion aggregates are fabricated by a subsequent self-assembly and spontaneous oxidation process. The results of magnetic measurements show that the PDI powders exhibit room-temperature ferromagnetism and a Curie temperature higher than 400 K, with a vast saturation magnetization that reaches ≈1.2 emu g-1 . Elemental analysis along with the diamagnetic signal of the ablated residue are used to rule out the possibility that the magnetism is due to metal contamination. The findings suggest that the long-range ferromagnetic ordering can survive at room-temperature in organic semiconductors, and offers a new optional way to create room-temperature magnetic semiconductors.

New Bioactive Fused Triazolothiadiazoles as Bcl-2-Targeted Anticancer Agents.

A series of 3-(6-substituted phenyl-[1,2,4]-triazolo[3,4-b]-[1,3,4]-thiadiazol-3-yl)-1H-indoles (5a–l) were designed, synthesized and evaluated for anti-apoptotic Bcl-2-inhibitory activity. Synthesis of the target compounds was readily accomplished through a reaction of acyl hydrazide (1) with carbon disulfide in the presence of alcoholic potassium hydroxide to afford the corresponding intermediate potassium thiocarbamate salt (2), which underwent cyclization reaction in the presence of excess hydrazine hydrate to the corresponding triazole thiol (3). Further cyclisation reaction with substituted benzoyl chloride derivatives in the presence of phosphorous oxychloride afforded the final 6-phenyl-indol-3-yl [1,2,4]-triazolo[3,4-b]-[1,3,4]-thiadiazole compounds (5a–l). The novel series showed selective sub-micromolar IC50 growth-inhibitory activity against Bcl-2-expressing human cancer cell lines. The most potent 6-(2,4-dimethoxyphenyl) substituted analogue (5k) showed selective IC50 values of 0.31–0.7 µM against Bcl-2-expressing cell lines without inhibiting the Bcl-2-negative cell line (Jurkat). ELISA binding affinity assay (interruption of Bcl-2-Bim interaction) showed potent binding affinity for (5k) with an IC50 value of 0.32 µM. Moreover, it fulfils drug likeness criteria as a promising drug candidate.

Synthesis and physical-chemical properties of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives and their evaluation for antimicrobial and diuretic activities

One of the most important tasks of our indigenous pharmaceutical science is the necessity for new medicines because existing drugs are characterized by various side effects, resistance, high toxicity, and so on. New bioactive molecule synthesis utilizes substances of natural origin as well as chemically modified ones. Thus, the researcher’s attention is mainly focused on 3-,7-,8-substituted derivatives of the natural heterocyclic xanthine system, which possess a wide range of pharmacological action. Synthesis of a novel of (3-benzyl-8-propylxanthin-7-yl)acetohydrazides with antimicrobial and diuretic activities described in the paper.
 The aim of this work is to develop efficient methods for synthesis of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives, and to study their physical-chemical properties.
 Materials and methods. Two-hour boiling of propyl 2-(3-benzyl-8-propylxanthine-7-yl)acetate by excess hydrazine hydrate in propan-2-ol medium have yielded the key the key intermediate 2-(3-benzyl-8-propylxanthine-7-yl)acetohydrazide. Further transformation of the latter has led to formation of corresponding acetohydrazide derivatives achieved by the reaction with aliphatic, aromatic, heterocyclic aldehydes, and ketones. The structure and the relative configuration of the synthesized compounds were elucidated by analyzing their physical-chemical data.
 Results. The synthesis and optimization of reaction conditions of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives were conducted. The identification of all synthesized compounds was aided by various physical-chemical methods (thin layer chromatography, elemental analysis, IR, and 1H NMR spectroscopy).
 Conclusions. As a result of synthetic research the preparative synthesis method of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives possessing antimicrobic, and diuretic activities was developed.

Design, Synthesis, and Antimicrobial Evaluation of Novel [1,2,4]Triazolo[3,4-b][1,3,4]thiadiazepine Derivatives

The title compounds, 3,3′,3″,3′′′-[methylenebis(oxybenzene-5,1,3-triyl)]tetrakis(6,8-diaryl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepines), were synthesized starting from dimethyl 4-hydroxyisophthalate which was reacted with dibromomethane to obtain tetramethyl 5,5′-[methylenebis(oxy)]di(benzene-1,3-dicarboxylate). The latter was treated with excess hydrazine hydrate, and the resulting tetrahydrazide was converted to tetrakis-1,2,4-triazolyl derivative via cyclization with ethanolic potassium hydroxide, carbon disulfide, and hydrazine hydrate. In the final stage, cyclocondensation with substituted chalcones afforded the target products. The structure of the newly synthesized compounds was confirmed by elemental analyses and FT-IR and NMR spectra, and their antimicrobial activities against some bacterial and fungal strains were estimated by the disc diffusion method.

Synthesis, structure and properties of 7-((4-amino-5-thio-1,2,4-triazole-3-yl)methyl)-theophylline derivatives

The combination of derivatives of 1,2,4-triazole and theophylline creates fertile soil for biologically active substances. The use of these heterocyclic systems allows the use of simple chemical modification methods and available reagents. This determines the relevance of the chosen direction of scientific research. The aim of the work was to study synthesis methods and study the properties of heterocyclic systems containing theophylline and 1,2,4-triazole fragment in their structure, create a chemical variety that was interesting from a scientific point of view and was promising in the search for biologically active substances. Materials and methods . Theophylline was used as the starting material. Using alkylation reactions, hydrazinolysis, interaction with a carbon disulfide followed by heterocyclization with an excess of hydrazine hydrate, 7-((4-amino-5-thio-1,2,4-triazole-3-yl)methyl)theophylline was obtained. The following stages of the chemical conversion included alkylation reactions with haloalkanes, the formation of azomethine compounds by reaction with aromatic aldehydes, and the reaction with aromatic carboxylic acid chlorides. The structure of the obtained compounds was confirmed by data of elemental analysis, 1H NMR spectroscopy and IR-spectrophotometry. The individuality of substances was established by using high performance liquid chromatography with diode-array and mass spectrometric detection. Results . S-alkylderivatives of 7-((4-amino-5-thio-1,2,4-triazole-3-yl)methyl)-theophylline, Schiff bases and carboxamides were synthesized, their structure was proved, and physical properties were investigated. The synthesized compounds have been subjected to the in silico molecular docking study against the kinases of anaplastic lymphoma by using the 2XP2 ligand, lanosterol 14-α-demethylase by using the 3LD6 ligand, cyclooxygenase-2 by using the ligand 4Z0L which were downloaded from the protein data bank (PDB). Conclusions . Molecular docking has shown the ability of the synthesized compounds to influence the kinase activity of anaplastic lymphoma, cyclooxygenase-2 and lanosterol-14-α-demethylase.

The synthesis and biological assessment of [[1,2,4]triazolo[4,3-a]pyridine-3-yl]acetamides with an 1,2,4-oxadiazol cycle in positions 6, 7 and 8

Fused heterocyclic 1,2,4-triazoles have provided much attention due to variety of their interesting biological properties.Aim. To develop the method for the synthesis of novel 2-[(1,2,4-oxadiazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl]acetamides and conduct the biological assessment of the compounds synthesized.Results and discussion. A diverse set of acetamides newly synthesized consists of 32 analogs bearing an 1,2,4-oxadiazole cycle in positions 6, 7 and 8. A convenient scheme of the synthesis starts from commercially available 2-chloropyridine-3-, 2-chloropyridine-4-, 2-chloropyridine-5-carboxylic acids with amidoximes to form the corresponding 2-chloro-[3-R1-1,2,4-oxadiazol-5-yl]pyridines, then follows the reaction of hydrazinolysis with an excess of hydrazine hydrate. The process continues via the ester formation with the pyridine ring closure, then the amide formations of the end products are obtained by hydrolysis into acetic acid.Experimental part. A series of new 2-[6-(1,2,4-oxadiazol-5-yl)-, 2-[7-(1,2,4-oxadiazol-5-yl)-, 2-[8-(1,2,4-oxadiazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl]acetamides were obtained in good yields, and their structures were proven by the method of 1H NMR spectroscopy. The prognosis and study of their pharmacological activity were also conducted.Conclusions. The synthetic approach of obtaining the representatives of 2-[(1,2,4-oxadiazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl]acetamides previously unknown can be used as an applicable method for the synthesis of diverse functionalized [1,2,4]triazolo[4,3-a]pyridine derivatives.

Synthesis of new potential biological active substances among 3-mercapto-4-amino-5-benzyl-1,2,4-triazol-4H derivatives

Conventional approaches to the formation of 1,2,4-triazole ring allow to introduce different substituents into the heterocyclic ring during the synthesis of key intermediates stage. In continuation of previous studies the synthesis of 3-mercapto-4-amino-5-benzyl-1,2,4-triazole-4H derivatives is described.
 The aim of investigation was synthesis of a series of new derivatives of 3-mercapto-4-amino-5-benzyl-1,2,4-triazole, proving their structure by physico-chemical methods and planning of pharmacological screening using PASS.
 Phenylacetic acid ethyl ester has been used for the synthesis as starting substance. It was subjected to hydrazinolysis to receive an appropriate hydrazide. In the next stage substance obtained was processed with hydrogen disulfide and appropriate potassium ditiokarbaminat has been received, which by reaction with an excess of hydrazine hydrate has been cyclised into a target 3-mercapto-4-amino-5-benzyl-1,2,4-triazol-4H. The first stage of chemical transformation reactions of key intermediate was its alkylation with chloroacetanilides under alkaline catalysis. By Paal–Knorr reaction the amino group in the synthesized alkylthio-4-amino-5-benzyl-1,2,4-triazole-4H was modified into pyrrole ring by the action of 2,5-dimethoxytetrahydrofuran in acetic acid medium.
 The structure of the compounds synthesized has been proved by 1H NMR spectroscopy. The successful alkylation of mercapto group indicates the disappearance of its proton signal at the spectra and appearance of the acetanilide residues protons signals. Modification of the amino derivatives into corresponding pyrrolyl substituted has been accompanied by the appearance of the triplet signals of magnet equivalent methyne protons of the pyrrole ring (protons at positions 3.4) at 6.30 ppm. The signals of the second pyrrole protons pair overlap with other aromatic protons signals.
 For the planning of pharmacological screening previous prognosis of the potential pharmacological activity spectrum has been carried out using software PASS. The prognosis showed that for all pyrrolyl substituted substances predominant in the spectrum of action was the influence on the central nervous system, and the probability of the activity of their synthetic precursors mainly limited to moderate antioxidant properties.

Synthesis and physical-chemical properties of 8-bromo-3-methyl-7-α-methylbenzylxanthine derivatives

The level of modern pharmaceutical science development is determined by the introduction in medical practice of new effective and non-toxic drugs. The problem of new drugs search depends on the presence in the arsenal of pharmacologists significant amount of original and promising bioactive compounds. In this aspect a special role is given to synthetic compounds of natural origin, which are successfully used in medical practice. Recent researches of national and foreign scientists suggest significant perspective synthetic xanthine derivatives in the creation of new drugs with various effects.
 The aim of this paper is synthesis of 8-bromo-3-methyl-7-α-methylbenzylxanthine derivatives, unspecified in scientific papers earlier, and to study their physical and chemical properties.
 The melting point has been determined by open capillary method on the device PTP (M). Elemental analysis has been performed on the device Elementar Vario L cube. NMR spectra have been taken using spectrometer Bruker SF-200.
 Synthesis of 8-bromo-3-methyl-7-α-methylbenzylxanthine was performed through boiling of 8-bromo-3-methylxanthine together with α-methylbenzylchloride. Having applied the reaction of the latter with an excess of a primary or secondary heterocyclic amine in the methoxyethanol environment, a range of corresponding 8-aminosubstituted 3-methylxanthine has been obtained. The heating of initial syntone with an excess of hydrazine hydrate in aqueous dioxane environment leads to the formation of 8-hydrazinoxanthine. Corresponding 8-(indolon-2-ylidene-3)-hydrazinoxanthines have been obtained through short-time heating up 8-hydrazinoxanthine with N-substituted isatin in aqueous dioxane environment. Structure of synthesized compounds has been definitely proved by NMR-spectroscopy.
 Simple laboratory method has been elaborated to synthesize 8-bromo-3-methyl-7-α-methylbenzylxanthine, which is initial compound for further chemical modification of xanthine molecule. Reactions of 8-bromo-3-methyl-7-α-methylbenzylxanthine with N-containing nucleophiles have been investigated. This allowed to obtain the previously undescribed 8-amino- and 8-hydrazinosubstituted 3-methyl-7-α-methylbenzylxanthine. Physical and chemical properties of new synthesized compounds have been studied. A synthetic perspective of the obtained substances has been shown.

Synthesis, molecular docking, and evaluation of novel bivalent pyrazolinyl-1,2,3-triazoles as potential VEGFR TK inhibitors and anti-cancer agents

Investigations in the discovery of tyrosinase enzyme inhibitors have the potential to design novel anti-cancer drugs. A variety of novel bivalent pyrazolinyl triazoles 5–7 were synthesized and identified. The bis-acetyl triazole 3 was accomplished via two-step process first by preparation of diazide 2 followed its coupling reaction with acetylacetone in basic medium. The Claisen–Schmidt condensation reaction of 3 with two moles equivalent of benzaldehyde produces the corresponding bis-α, β-unsaturated ketone 4. Treatment of Schiff base 4 with excess hydrazine hydrate in either acetic acid or ethanol/DMF afforded the bis-N-acetylpyrazline 5 or bis-pyrazoline 6, respectively. Finally, treatment of 6 with two derivatives of isothiocyanate analog gives the bis-N-thioamide pyrazolines 7a and 7b. The synthesized compounds were evaluated as anti-tumor candidates against three human cancer cell lines (MCF-7, HepG2, and HCT-116). The bioscreening evaluation showed that compounds 7a and 6 had a significant antineoplastic potencies (IC50: 32.26 and 57.06 µg/mL) against breast MCF-7 and hepatic HepG2 cancerous cell lines, respectively, in relative to the standard drug, 5-fluorouracil. Molecular docking studies of the synthesized compounds were investigated as VEGFR2 TK inhibitors.

Egg-like magnetically immobilized nanospheres: A long-lived catalyst model for the hydrogen transfer reaction in a continuous-flow reactor

A novel egg-like nanosphere was designed as a long-lived catalyst and is described as Fe3O4@nSiO2-NH2-Fe2O3•xBi2O3@mSiO2. The catalyst was prepared using a modified Stober method with template-free surface-protected etching. The catalyst particle consists of a magnetic Fe3O4 core as the “yolk”, an inner silica shell bearing active Fe2O3•xBi2O3 species as the “egg white”, and outer mesoporous silica as the “egg shell”. It exhibits an excellent performance in the catalytic reduction of nitro aromatics to corresponding anilines in a fixed-bed continuous-flow reactor. The reaction could be performed at 80 °C and could reach complete conversion in less than 1 min with only a 7% excess of hydrazine hydrate. The catalyst bed could be easily shifted between different substrates without cross-contamination because of the uniformity of the catalyst particles. This catalyst exhibited very good stability in the continuous-flow protocol. In the long-term reduction of p-nitrophenol with 0.5 mmol·min−1 productivity, it worked for more than 1,500 cycles without any catalytic activity loss.

Synthesis and structure of new 4-amino-5-(2-R1-phenyl)-1,2,4-triazole-3-thiol alkilderivatives

Chemistry of heterocyclic systems is a separate branch of organic chemistry with a long history and future prospects. The ring system of 1,2,4-triazole continuously attracts the interest of chemists, pharmacologists and pharmacists in finding medicinal compounds through its universal potential interactions with biological systems. Today it is known that 1,2,4-triazole derivatives have antibacterial, antifungal, antiinflammatory, anticonvulsant, antiviral, antituberculosis, antioxidant, anticancer and antitumor activities. They also have analgesic, local anesthetic, antimalarial, antiproliferative effects, antihypertensive, antidepressant, sedative, antihistamine, hepatoprotective, hypoglycemic, diuretic, antipyretic and countless number of action types. Therefore, the search of biologically active remedies and creating of new drugs on its base is highly efficient topical issue of medical and pharmaceutical work. The purpose of these studies is the synthesis, establishment of physical-chemical parameters of new 4-amino-5-(2-R 1 -phenyl)-1,2,4-triazole-3-thiol alkylderivatives. Materials and methods . The studying of physical and chemical properties of compounds was made in accordance with the methods described in the State Pharmacopoeia of Ukraine 2.0. The melting point was determined on an automatic gear MPA100. The elemental composition of the compounds was set on the analyzer Elementar Vario EL cube. 1 H NMR spectra were recorded using the spectrometer Varian Mercury VX-200 (1H, 200 MHz) and decrypted by a computer program SpinWorks 3.1.8. Chromatography-mass spectral studies were carried out in the gas-liquid chromatograph Agilent 1260 Infinity HPLC equipped with a mass spectrometer Agilent 6120 (in electrospray ionization (ESI)). Results. 4-amino-5-phenyl-4 H -1,2,4-triazole-3-thiol and 4-amino-5-(2-bromophenyl)-4 H -1,2,4-triazol-3-thiol were used as the initial materials. These compounds were obtained by reaction of benzoic acid hydrazide and 2-brombenzoic acid hydrazide with the excess of carbon disulfide in a solution of potassium hydroxide in butanol-1. In the future double excess of hydrazine hydrate was added to the synthesized products and mixture was heated for 3 hours. Then cooled and neutralized with hydrochloric acid. Thus the initial thiols were obtained. Individual peaks of derived compounds were established in carrying out the chromatography-mass spectral studies which correspond to theoretical calculations of atomic masses. Thus on the chromatogram of (5-(hexylthio)-3-phenyl-4H-1,2,4-triazole-4-amine, molecular weight 276,40) there are signals with m/z 277.1 and 279.1, which confirm the structure of obtained compound. Conclusions . 12 new alkylderivatives of 4-amino-5-(2-R 1 -phenyl)-1,2,4-triazole-3-thiol were synthesized in the result of the study. The structure of derived substances was confirmed by elemental analysis, 1 H NMR spectroscopy and chromatography-mass spectrometry.

ChemInform Abstract: Synthesis of 4‐Arylamino‐3‐(trifluoromethyl)pyridazines and Pyridazino[3,4‐b]quinoxalines (as By‐Products) from 3‐Aroylmethyl‐2‐(trifluoromethyl)quinoxalines and Hydrazine Hydrate.

A number of 4-arylamino-3-(trifluoromethyl)pyridazines were obtained in good yields via the novel reaction of 3-aroylmethyl-2-(trifluoromethyl)quinoxalines with an excess of hydrazine hydrate in refluxing n-butanol with or without acetic acid. This reaction is accompanied by the formation of side-products with the pyridazino[3,4-b]quinoxaline skeleton. The possible reaction mechanism was discussed.

Transformations of β-aryl-N-Cbz-α,β-didehydro-α-amino esters with hydrazine hydrate

Abstract Cyclizations of Cbz-protected α,β-didehydro-β-arylalanine esters 1 with excess hydrazine hydrate afforded mixtures of the expected 3-pyrazolidinones 2 and the unexpected 1-amino-5-benzylidenehydantoins 6 and N-Cbz-β-arylalanine hydrazides 7. Presumably, the pyrazolidinones 2 and hydantoins 6 are formed as primary products via competitive 1,2- and 1,4-addition of hydrazine hydrate followed by cyclization, whereas β-arylalanine hydrazides 7 are formed as secondary products via reductive cleavage of the C(5)–N(1) bond in pyrazolidinones 2. The overall selectivity depends on the reaction time and on the β-substituent in the starting dehydroalanine ester 1.

Design, Synthesis, Characterization, and Antimicrobial Screening of Novel Indazole Bearing Oxadiazole Derivatives

Ethyl 2‐(2,6‐dioxocyclohexyl)‐2‐oxoacetate was prepared by reacting cyclohexane‐1,3‐dione (1) and diethyl oxalate (2) with the help of sodium ethoxide in ethanol at 0–5°C. Subsequent treatment of ethyl 2‐(2,6‐dioxocyclohexyl)‐2‐oxoacetate with hydrazine hydrate in ethanol resulted into ethyl 4‐oxo‐4,5,6,7‐tetrahydro‐2H‐indazole‐3‐carboxylate while without solvent in excess hydrazine hydrate on reflux resulted into 4‐oxo‐4,5,6,7‐tetrahydro‐2H‐indazole‐3‐carbohydrazide (3). The synthesis of novel indazole bearing oxadiazole derivatives (ODZ 01 to 16) has been achieved by the reaction of hydrazide of 2H‐indazole (3) with acid (4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j, 4k, 4l, 4m, 4n, 4o, 4p) in the presence of POCl3, and the antimicrobial activity of synthesized novel compounds has been studied.

Synthesis of 4-arylamino-3-(trifluoromethyl)pyridazines and pyridazino[3,4-b]quinoxalines (as by-products) from 3-aroylmethyl-2-(trifluoromethyl)quinoxalines and hydrazine hydrate

A number of 4-arylamino-3-(trifluoromethyl)pyridazines were obtained in good yields via the novel reaction of 3-aroylmethyl-2-(trifluoromethyl)quinoxalines with an excess of hydrazine hydrate in refluxing n-butanol with or without acetic acid.