Condensation Of Hydrazine Research Articles

New Synthesis of 3-Aminohydantoins via Condensation of Hydrazines with Isocyanates Derived from α-Amino Esters

AbstractA new, simple, and efficient method for the synthesis of 3-aminohydantoins was reported in two steps, starting from the corresponding l -amino esters. Commercially available α-amino esters were converted into the corresponding isocyanate derivatives, which were then subjected to the condensation reaction with hydrazine hydrate and arylhydrazines, in the presence of DMAP and DIPEA. This method provides the corresponding 3-aminohydantoins in moderate and good yields under a simple and practical protocol.

New2-((2-(2,4-dinitrophenyl)hydrazineeylidene) derivatives: design, synthesis, in silico, and in vitro anticancer studies

A series of novel hydrazone compounds have been synthesized by the condensation of hydrazines and different substituted salicylaldehydes at a molar ratio of 1:1 in one step reaction and characterized by FT-IR, ESI-MS, 1H NMR, and single crystal x-ray diffraction. The crystal structure of the compound shows a trans configuration around the C = N bond and triclinic system with P −1/-p 1. Synthesized compounds were screened for cytotoxicity activities against A375 (melanoma), HT-29 (Colon), and A549 (lung) cancer cell lines. Among them, compound 2 exhibited the highest cytotoxic effect against the A375 cell line (IC50 = 0.30 µM) and HT-29 cell line (1.68 µM), compared to those of apatinib as a reference standard drug (0.28, 1.49 µM, respectively). The cytocompatibility assay on the L929 normal cell line and the hemolysis assay on human RBC were used to validate the non-toxic action. From DFT calculation, the various parameters such as HOMO-LUMO energies, Hirshfeld, and MEP have been studied. Furthermore, in silico molecular docking with three receptors was studied. Among four compounds, compound 2 has the lowest binding energy against cyclin dependent kinase (ΔGb = −9.3 kcal/mol). In addition to this, molecular dynamics (MD) simulation was also performed. Based on this study, these novel hydrazones can be considered a promising anticancer agent due to their potent cytotoxicity activities and computational analysis. Communicated by Ramaswamy H. Sarma

Self-Assembly of a U(VI)-Containing Polytungstate Tetramer with Lewis Acid-Base Catalytic Activity for a Dehydration Condensation Reaction.

A novel U(VI)-containing polytungstate (U-POW) tetramer, {K1.37Na26.63[K2(UO2)4Cl0.5(OH)5.5(γ-SiW10O36)4]}·ca66H2O (U4), was synthesized using the Keggin-type precursor [γ-SiW10O36]8- and UO2(NO3)2. U4 was further characterized by single-crystal X-ray diffraction, FT-IR, Raman spectroscopy, solid-state diffuse reflection spectroscopy, ICP-OES, ESI-MS, TGA, and PXRD. The central {K2(UO2)4Cl0.5(OH)5.5} chromophore was constructed dexterously from four uranyl, four halves of K ions, 5.5 bridging μ2-OH, and disordered Cl ions, and was further stabilized by four {γ-SiW10} moieties to construct the tetramer [K2(UO2)4Cl0.5(OH)5.5(γ-SiW10O36)4]28-. Notably, U4 could work as an effective bifunctional Lewis acid-base catalyst for the synthesis of pyrazoles via the condensation of hydrazines with 1,3-diketones under mild conditions, which is attributed to the synergetic effect of the Lewis acidity of U(VI) and the Lewis basicity of {γ-SiW10}.

Synthesis of 3-Aryl-Substituted 4-Aminopyrazoles from Acetophenones

AbstractA synthetic methodology for a protecting-group-free formation of 3-aryl-substituted 4-aminopyrazoles from acetophenones via a telescoped oximation and hydrazine condensation of 1,3-ketoaldehydes to generate nitrosopyrazoles, and copper-catalyzed NaBH4 reduction of the nitroso group, was demonstrated. The synthesis tolerates a broad scope of substrates with a variety of substituents on the phenyl ring to afford the desired products.

Revisit: The Synthesis of 3-amino pyrazoles promoted by p-toluenesulfonic acid as an efficient catalyst under solvent and solvent-free conditions

Revisit: The Synthesis of 3-amino pyrazoles promoted by p-toluenesulfonic acid as an efficient catalyst under solvent and solvent-free conditions

Development and Scale-Up of a Continuous Manufacturing Process for a Hydrazine Condensation Reaction

The development of a continuous manufacturing process for a hydrazine condensation reaction at high temperature is reported. This continuous process represents a safer approach to manufacture 3-phe...

Preparation and Antitubercular Activities of Palindromic Hydrazinecarbothioamides and Carbonothioic Dihydrazides

Background:With approximately one-third of the world’s population infected, tuberculosis continues to be a global public health crisis. The rise of strains that are unusually virulent or highly resistant to current drugs is a cause of special concern, prompting research into new classes of compounds, as well as the re-evaluation of known chemotherapeutic agents.Objectives:The antimycobacterial activities associated with some recently-reported thiocarbonyl compounds kindled our interest in the synthesis of substituted hydrazinecarbothioamides (3) and carbonothioic dihydrazides (4), with the aim of investigating their potential in antitubercular drug design and discovery.Methods:In the present study, the title compounds 3 and 4 were prepared by the condensation of hydrazines with isothiocyanates in reactions readily controlled by stoichiometry, temperature and solvent. The compounds were assessed against Mycobacterium bovis BCG in Kirby-Bauer disc diffusion, and minimum inhibitory concentrations were determined against the virulent strain M. tuberculosis Erdman.Results:The chemical structures of these thermally stable compounds were determined by IR, 1HNMR, 13C-NMR, high-resolution mass spectrometry and elemental analysis. In the Kirby-Bauer disc diffusion assay, some of the compounds showed substantial diameters of inhibition against BCG. In some cases, the zones of inhibition were so large that no growth at all was observed on the assay plates. Against M. tuberculosis Erdman, several of the compounds showed significant activities. Compound 3h was the most active, demonstrating a minimum inhibitory concentration of 0.5 µg/mL.Conclusion:We found that the title compounds may be prepared conveniently in excellent purity and good yields. They are readily identified on the basis of their characteristic spectra. Some members of this class showed significant activities against mycobacteria. We conclude that further work will be warranted in exploring the antitubercular properties of these compounds.

Hydrazone-linked soybean protein isolate-carboxymethyl cellulose conjugates for pH-responsive controlled release of pesticides

To improve the utilization of pesticides and reduce the amount of pesticides used, sustained-release nanoparticles were prepared. Soybean protein isolate (SPI) and carboxymethyl cellulose (CMC) were modified to obtain hydrazine-modified SPI and aldehyde-modified CMC, respectively, and SPI-CMC was prepared by the condensation of hydrazine and aldehyde groups, forming a hydrazone bond. SPI-CMC was heated and loaded with avermectin (AVM) to obtain AVM/SPI-CMC. The encapsulation efficiency property, anti-ultraviolet property, sustained-release characteristics, pH responsiveness, and toxicological profiles were studied. The particles in the formulation were spherical-like, with sizes ranging between 150 and 250 nm. The encapsulation efficiency increased with the addition of SPI, which reached 44.49% when SPI was added in a mass ratio of mSPI-HYD:mCMC-ALD = 2:1. The percentage of remaining AVM in AVM/SPI-CMC was 31.47% higher than that in the AVM solution after UV irradiation for 43 h. Moreover, the nanoparticles were responsive to pH. SPI-CMC had no significant effect on the insecticidal toxicity of AVM. Environmental friendly SPI-CMC could protect and release pesticides continuously, which could improve the efficiency of pesticides. Soybean protein isolate (SPI) was bonded to carboxymethyl cellulose (CMC) by a hydrazine bond to prepare SPI-CMC carriers for pesticide applications. AVM/SPI-CMC was obtained by encapsulating avermectin (AVM) with SPI-CMC through thermal denaturation. SPI-CMC could improve the anti-UV performance of AVM and slow down the decomposition rate of AVM. The hydrazone bond and carboxyl groups showed pH responsiveness, which could release drugs rapidly in an acidic environment. Environmentally friendly SPI-CMC could protect and release pesticides continuously, which could improve the efficiency of pesticides.

Synthesis and evaluation of tetrahydropyrazolopyridine inhibitors of anion exchange protein SLC26A4 (pendrin).

Pendrin is a transmembrane chloride/anion antiporter that is strongly upregulated in the airways in rhinoviral infection, asthma, cystic fibrosis and chronic rhinosinusitis. Based on its role in the regulation of airway surface liquid depth, pendrin inhibitors have potential indications for treatment of inflammatory airways diseases. Here, a completely regioselective route to tetrahydro-pyrazolopyridine pendrin inhibitors based on 1,3-diketone and substituted hydrazine condensation was been developed. Structure-activity relationships at the tetrahydropyridyl nitrogen were investigated using a focused library, establishing the privileged nature of N-phenyl ureas and improving inhibitor potency by greater than 2-fold.

Synthesis, molecular structure analyses and DFT studies on new asymmetrical azines based Schiff bases

In this paper, we report the synthesis of new unsymmetrical azines Schiff bases. These compounds were prepared by condensation of hydrazine with different aldehydes and ketones to give (E) -2-hydroxynaphthalene-1-carbaldehyde [(1E) -2-thienylmethylene] hydrazone compound (I) and (Z) - 2 - [(E) -1- (2-hydroxyphenyl) ethylidenehydrazin-1-ylidene] -1,2-diphenylethanone compound (II). The method adopted consists in reacting the two different carbonyl compounds simultaneously in one step in a stepwise manner reported which is practical and cost-effective. The reaction with a minor modification in operating conditions proceeded efficiently and with excellent performance. The structure of each of the two compounds (I) and (II) was determined by the X-ray diffraction technique performed on single crystals. The asymmetric unity of the two molecules consists of one asymmetry-independent molecule. In addition, hydrogen bonds CH … π are observed in the compound (II). We then present a detailed DFT study based on B3LYP/6-31G (d, p) geometric structures of compounds (I); (II) and another compound (III) also another asymmetric azine (Z) -2 - [(E) -2-benzylidenehydrazine-1-ylidene] -1,2-diphenylethanone whose crystal structure is reported. The fundamental vibration wave numbers are calculated and a good agreement between the observed and calculated wave numbers is obtained. The study was extended to the HOMO-LUMO analysis to calculate the energy gap. The calculated HOMO and LUMO energy reveals that the charge is transferred into the molecule.

Building Diversity in ortho-Substituted s-Aryltetrazines By Tuning N-Directed Palladium C–H Halogenation: Unsymmetrical Polyhalogenated and Biphenyl s-Aryltetrazines

We report a general route for synthesizing ortho-substituted unsymmetrical biphenyl and polyaromatic s-aryltetrazines. These compounds are inaccessible by classical Pinner hydrazine condensation or by the current s-aryltetrazine aromatic core functionalization methods described up to now. We exploited multiple versatile N-directed palladium C–H activation/halogenation of s-aryltetrazine to form C–X bonds (X = I, Br, Cl, F), which collectively produced polyhalogenated unsymmetrical building blocks. We achieved a sequence of selective C–H halogenation reactions in a specific order to produce reactive aryl halides. Polyhalogenated s-aryltetrazines can then be used for controlled cross-coupling reactions toward ortho-substituted polyaromatic s-aryltetrazines. In general, this C–H functionalization route gives access to a large number of variously halogenated building blocks practical for further synthetic implementation of tetrazines (arylation, cycloaddition, etc.). Herein, we exemplified their potential by ...

Divergent Synthesis of 1H‐Indazoles and 1H‐Pyrazoles from Hydrazones via Iodine‐Mediated Intramolecular Aryl and sp3 C–H Amination

AbstractA divergent intramolecular C–H amination of hydrazones has been developed employing molecular iodine (I2) as the sole oxidant. The required hydrazone substrates were readily obtained by condensation of hydrazines with the corresponding ketones. In the presence of potassium iodide, I2‐mediated oxidative cyclization of diaryl and tert‐butyl aryl ketone hydrazones produced 1H‐indazoles via direct aryl C–H amination. Under similar reaction conditions, primary and secondary alkyl ketone hydrazones were transformed into 1H‐pyrazole products in a reaction involving sp3 C–H amination. This synthetic methodology does not involve transition metals, and is operationally simple, providing a facile access to indazole and pyrazole derivatives in an efficient and scalable fashion.magnified image

The synthesis of 4-amino -5-(pyridin-2(3)-Yl) -1,2,4-triazole (4H)-3-ylthio acetamide derivatives as potential anti-inflammatory substances

Aim. A targeted synthesis of the potential anti-inflammatory agents – 4-amino-5-(pyridin-2-yl)- and 4-amino-5-(pyridin-3-yl)- 1,2,4-triazole (4H)-3-ylthio acetamides.Materials and methods. The standard methods of organic synthesis, microwave synthesis, physico-chemical methods to proof the structure of the synthesized compounds were used for this work.Results. Initial 4-amino-3-mercapto-5-(pyridine-2 (3)-yl)-4H-1,2,4-triazoles obtained from carboxylic acids hydrazides through the stage of obtaining of appropriate potassium dithiocarbazinate followed by condensation of hydrazine in the traditional boiling ethanole and microwave irradiation without solvent. The appropriate thioacetamides derivatives were obtained by alkylation of 4-amino-3-mercapto-5-(pyridin-2 (3)-yl)-4H-1,2,4-triazole by N-aryl substituted б-chloroacetamides in conditions of alkaline catalysis.Conclusion. The synthesis of potential anti-inflammatory substances – 4-amino-5-(pyridin-2 (3)-yl)-1,2,4-triazole(4H)-3-ylthio acetamides was planned and carried out. It was established, that the initial intermediates synthesis – 4-amino-3-mercapto-5-(pyridine-2 (3)-yl)-4H-1,2,4-triazoles – can be carried out without solvent and without the use of lead acetate. For the compounds synthesized, pharmacological screening for anti-inflammatory activity was planned

Synthesis and Modular Reactivity of Pyrazole 5-Trifluoroborates: Intermediates for the Preparation of Fully Functionalized Pyrazoles.

The regioselective condensation of hydrazines and ynone trifluoroborates provides access to a range of pyrazole 5-trifluoroborates. The stability of the borate unit allows chemoselective halogenation of the heteroaromatic ring, thereby delivering pyrazole scaffolds that allow orthogonal functionalization at C5 and C4. The modular reactivity of these intermediates is exemplified by cross-coupling reactions, enabling regiocontrolled synthesis of fully functionalized pyrazole derivatives.

Structural basis of the substrate recognition of hydrazidase isolated from Microbacterium sp. strain HM58-2, which catalyzes acylhydrazide compounds as its sole carbon source

Hydrazidase was an enzyme that remained unidentified for a half century. However, recently, it was purified, and its encoding gene was cloned. Microbacterium sp. strain HM58-2 grows with acylhydrazides as its sole carbon source; it produces hydrazidase and degrades acylhydrazides to acetate and hydrazides. The bacterial hydrazidase belongs to the amidase signature enzyme family and contains a Ser-cisSer-Lys catalytic motif. The condensation of hydrazine and carbonic acid produces various hydrazides, some of which are raw materials for synthesizing pharmaceuticals and other useful chemicals. Although natural hydrazide compounds have been identified, the metabolic systems for hydrazides are not fully understood. Here, we report the crystal structure of hydrazidase from Microbacterium sp. strain HM58-2. The active site was revealed to consist of a Ser-cisSer-Lys catalytic triad, in which Ser179 forms a covalent bond with a carbonyl carbon of the substrate. 4-Hydroxybenzoic acid hydrazide bound to the S179A mutant, showing an oxyanion hole composed of the three backbone amide groups. Furthermore, H336 in the non-conserved region in the amidase family may define the substrate specificity, which was confirmed by mutation analysis. A wild-type apoenzyme structure revealed an unidentified molecule covalently bound to S179, representing a tetrahedral intermediate.

Visible-Light Photocatalytic Aerobic Annulation for the Green Synthesis of Pyrazoles.

A selective and high yielding synthesis of polysubstituted pyrazoles through a VLPC (visible light photoredox catalysis)-promoted reaction of hydrazine with Michael acceptors is reported. The method employs very mild reaction conditions and uses air as the terminal oxidant, which makes the process environmentally benign. Different types of Michael acceptors with various substituents can undergo the reaction to afford corresponding pyrazoles in good to excellent yields. The reaction is proposed to go through VLPC-promoted oxidation of hydrazine to diazene followed by its addition to Michael acceptors, other than the conventional condensation of hydrazine with a carbonyl.

Synthesis, regioselectivity, and DFT analysis of new antioxidant pyrazolo[4,3-c]quinoline-3,4-diones

The condensation of hydrazine, N-methylhydrazine, and N-phenylhydrazine with ethyl 4-chloro-2-oxo-1,2-dihydroquinoline-3-carboxylate derivatives has been investigated. As a result, 12 new antioxidant pyrazolo[4,3-c]quinolin-3,4-diones were obtained with good to high yields. When two cross-products could be possible, only one isomer bearing the methyl or the phenyl group at the N1 position is isolated and unequivocally characterized using 1D and 2D NMR techniques, FT-IR, and combustion analyses. DFT analysis of the reaction mechanism was carried out in the Pearson’s hard soft acid base framework, confirming the assigned structure to the observed pyrazolo[4,3-c]quinolin-3,4-diones. These calculations indicate a favored kinetic control for the synthesized pyrazolo[4,3-c]quinolin-3,4-diones compared to its possible regioisomer.

ChemInform Abstract: A Convenient Four‐Component One‐Pot Strategy Toward the Synthesis of Pyrazolo[3,4‐d]pyrimidines.

An efficient one-pot synthesis of pyrazolo[3,4-d]pyrimidine derivatives by the four-component condensation of hydrazines, methylenemalononitriles, aldehydes and alcohols has been developed via two different reaction pathways. The structures of target products were characterized by IR spectroscopy, NMR ((1)H and (13)C) spectroscopy and HRMS (ESI) spectrometry. The crystal structure of 4-ethoxy-6-(2-nitrophenyl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine was determined by single crystal X-ray diffraction.

FLUOROUS SUPPORTED SYNTHESIS OF PYRAZOLONE DERIVATIVES FROM ALLYLIC ALCOHOLS USING A PALLADIUM-CATALYZED STRATEGY

Ten substituted pyrazolone derivatives were easily synthesized from perfluorinated allylic alcohols, via a straightforward two steps reaction involving a Heck-coupling/isomerization reaction and subsequent condensation of hydrazines. This fluorous supported methodology, that combines a cyclo-release approach and F-SPE purification allows for the obtaining of the final products with a good purity.

One-pot synthesis of new derivatives of 3,4-dihydropyrimidinone, and substituted imidazolin-2-ones

Three-component condensation of arylglyoxals, acetylacetone and urea in EtOH in the presence of small amounts of HOAc gives rise to 5-acetyl-4-aroyl-6-methyl-3,4-dihydropyrimidinones or 5-aryl-1,3-dihydro-2H-imidazol-2-ones containing an acetylacetone fragment in position 4. (1HPyrazol-4-yl)-1,3-dihydro-2H-imidazol-2-one derivatives were obtained via the reaction of the latter compounds with hydrazine. Doubt is cast upon an earlier report of the formation of pyrimido-pyridazines by condensation of hydrazines with 5-acetyl-4-aroyldihydropyrimidinones.