Reaction Of Piperazine Research Articles

Parallel Synthesis of Piperazine Tethered Thiazole Compounds with Antiplasmodial Activity.

Thiazole and piperazine are two important heterocyclic rings that play a prominent role in nature and have a broad range of applications in agricultural and medicinal chemistry. Herein, we report the parallel synthesis of a library of diverse piperazine-tethered thiazole compounds. The reaction of piperazine with newly generated 4-chloromethyl-2-amino thiazoles led to the desired piperazine thiazole compounds with high purities and good overall yields. Using a variety of commercially available carboxylic acids, the parallel synthesis of a variety of disubstituted 4-(piperazin-1-ylmethyl)thiazol-2-amine derivatives is described. the screening of the compounds led to the identification of antiplasmodial compounds that exhibited interesting antimalarial activity, primarily against the Plasmodium falciparum chloroquine-resistant Dd2 strain. The hit compound 2291-61 demonstrated an antiplasmodial EC50 of 102 nM in the chloroquine-resistant Dd2 strain and a selectivity of over 140.

A Short Review on Structural Concepts of Metal Complexes of Proton Transfer Salts of Pyridine-2-Carboxylic Acid

In this study, a brief review of the proton transfer salts synthesized from the reaction of piperazine with pyridine-2-carboxylic acid and their metal complexes since 2009 was made. The metals in the studied compounds are mostly d-block metals. In complexes, the anionic component of the salt is coordinated to the metal, while the cationic component is present only as a complementary ion in a complex.

Synthesis of a bio‐based piperazine phytate flame retardant for epoxy resin with improved flame retardancy and smoke suppression

AbstractPiperazine phytate (PIPT), a bio‐based nitrogen‐phosphorus containing flame retardant, was feasibly synthesized by the reaction of piperazine (PI) with phytic acid (PA) in ethanol. The structure and chemical composition of PIPT were systematically characterized by NMR, FTIR, XRD, TEM and EDX. Epoxy resin (EP) composites with PIPT were prepared by utilizing 4, 4′‐diaminodiphenylmethane as a curing agent. The flame retardancy, mechanical performances and thermal decomposition of the EP composites were studied. The results show that the EP composite containing 15 wt% PIPT (sample EP/15PIPT) passes UL‐94 V0 rating with a limiting oxygen index reaching 35.5%. The cone calorimetric tests results demonstrate the peak heat release rate and total smoke release of EP/15PIPT are about 51.4% and 44.9% reduced than which of pure EP, respectively. The morphology of residual char reveals that the EP/ PIPT composites can form good and compact char during the combustion. In comparison with pure EP, the mechanical performances of the EP/PIPT composites decrease slightly as PIPT content increases.

Piperazinium Nano Silica Sulfonate: An Efficient Catalyst for the Hantzsch Reaction

AbstractPiperazinium nano silica sulfonate (PNSS) is simply prepared by the reaction of piperazine with nano sized silica sulfuric acid. After preparation it was completely characterized using different techniques including FT‐IR, XRD, TGA, FESEM, EDS and TEM analysis. In continue PNSS was efficiently used for the promotion of the synthesis of polyhydroquinolines and 1,8‐dioxo‐decahydroacridines through unsymmetrical and symmetrical Hantzsch condensation reaction. High yields, short reaction times, ease of preparation and reusability of the catalyst, easy work‐up procedure and solvent‐free conditions are among the most important advantages of this method.

High-permeability and anti-fouling nanofiltration membranes decorated by asymmetric organic phosphate

Aiming at the two challenging bottlenecks of “trade-off effect” and “membrane fouling” that limit the development of nanofiltration (NF) membranes, this work developed a high-performance NF membrane based on the modification by an asymmetric hydrophilic zoledronic acid (ZA). ZA plays multiple roles: (1) the self-restrictive diffusion effect of piperazine (PIP)/ZA obtained from the reaction of PIP and ZA resulted in smooth membrane surface; (2) the imidazolyl on ZA uninvolved in interfacial polymerization (IP) led to enlarged polyamide network pores and provided more solvent tunnels; (3) all groups of ZA improved the membrane hydrophilicity; (4) the electronegative phosphate groups made a significant contribution to the strong membrane surface electronegativity. As a result, the ZA-modified membrane exhibited nearly five times higher permeability than that of traditional NF membranes, accompanied by perfect selectivity of SO42− and Cl− as well as the outstanding anti-fouling property, indicating its enormous application prospect in water treatment.

Synthesis and characterization of unsaturated diacyl and alkyl-acyl piperazinederivatives

The aim of this study is to obtain new unsaturated piperazine compounds by the reactions of piperazine (1a) and piperazine derivatives (1b-1d) with acylation reactive groups (a-2j). Methacryloyl piperazine (1b) was synthesized from the reaction of methacrylic anhydride with piperazine (1a). Acyl chlorides (2b-2d) were prepared from the reaction of thionyl chloride with carboxylic acids (3a-3c) obtained as a result of the reaction with malonic acid and suitable aldehyde (5-methylfuran-2-carbaldehyde for 3a, cinnamaldehyde for 3b, and thiophene-2-carbaldehyde for 3c), respectively, by literature methods. Acyl chlorides 2ed and 2f }were obtained from the reaction of commercially purchased carboxylic acids 3d and 3e with thionyl chloride. Acyl chlorides (2g-2j) were synthesized from the reaction of thionyl chloride with carboxylic acids (3d-3g) transformed from hydrolyzation of esters (4a-4d}) obtained as a result of the reaction of triethyl phosphonoacetate with a suitable ketone (acetophenone for 4a, benzophenone for 4b, 1-(5-methylfuran-2-yl)ethan-1-one for 4c, and 1-(thiophen-2-yl)ethan-1-one for 4d), respectively, by literature methods. Unsaturated piperazine derivatives 5a and 5b were obtained from the reaction of 1bwith 2b and 2e, respectively. In addition, from the reaction of 1b and acyl chlorides (2b-2j), unsaturated piperazines (5c-5k) were synthesized in medium to good yields (63%-84%). Also, 5l-5g-and 5r-5w were obtained from the reaction of allyl piperazine (2c) and cinnamyl piperazine (2d) with acyl chlorides (2a-2f).

1,4-Bis(2-nitrobenzyl)piperazine

The title compound, C18H20N4O4, was synthesized via the base-assisted reaction of piperazine and 2-nitrobenyl bromide in toluene: the complete molecule is generated by a crystallographic inversion centre in the solid state.

Sulfonylpiperazines based on a flavone as antioxidant and cytotoxic agents.

Chrysin-based sulfonylpiperazines 7a-k were synthesized and investigated for their in vitro free radical scavenging potential as well as cytotoxic efficacies against selected cancer cell lines. Cytotoxicity of the new compounds toward noncancer cells was confirmed using the SRB assay against Madin-Darby Canine Kidney cells. Reaction of piperazine with different substituted benzenesulfonyl chlorides in triethylamine furnished sulfonylpiperazines (3a-k), which were then allowed to react with 7-(4-bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one (6) prepared reacting chrysin with 1,4-dibromobutane to give the final derivatives 7a-k. The results concluded that chrysin-sulfonylpiperazines exerted better antioxidant and anticancer efficacies than previously studied chrysin-piperazine precursors. For example, compounds 7h, 7j, and 7k with 4-OCF3 , 4-OCH3 , and 2,4-diOCH3 groups exhibited the best antioxidant potential against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals. Moreover, halogenated analogues (7b, 7c, 7g, and 7h) demonstrated promising anticancer potential against SK-OV3, HeLa, and HT-29 cell lines, whereas those bearing a methoxy functional group (7j and 7k) had beneficial effects against the cell lines A-549 and HT-29. Thus, it can be confirmed from the bioassay results that the overall structural design as well as proper substitution is crucial to deliver the anticipated biological effects. Spectroscopic techniques such as FT-IR, 1 H NMR, 13 C NMR, mass and elemental analysis (CHN) were carried out to confirm the final structures.

Determination of the effect of proteoliposome concentration on Aquaporin Z incorporated nanofiltration membranes

ABSTRACT We report on the fabrication of AqpZ immobilized flat sheet membranes. The effects of interfacial polymerization conditions as well as proteoliposome concentration were evaluated. Commercial AqpZ were used as positive control for cloned AqpZ. Specific permeate flux of membranes at higher proteoliposome concentrations increased up to 25 times higher than thin film composite membranes; however; MgSO4 rejection is lowered almost to 1.5%. FTIR and SEM confirm immobilization of proteoliposomes. Thermal analysis showed that increasing proteoliposome concentration has no positive effect on the incorporation of proteoliposomes into polyamide structures. On the contrary, at lower proteoliposome concentrations, incorporation of proteoliposomes was found better. When combined membrane performances were compared in terms of specific permeate flux; MgSO4 and humic rejection and flux recovery after humic acid filtration, the performance of cloned AqpZ incorporated membranes (having 0.1 mg/mL proteoliposome concentration and polyamide formed with 2 min piperazine reaction time) improved 1.7 times regarding TFC membranes. According to the results, increasing proteoliposome concentration did not improve nanofiltration membrane performance. On the contrary, lower proteoliposome concentrations were found to be more effective in increasing membrane performance.

1,4‐Piperazinium Hydrogen Sulfate {[H‐pi]HSO4} a Novel Di‐Cationic Ionic Liquid: Synthesis, Characterization and Its Applications as a Catalyst in Various Organic Transformations

AbstractIn this work, a new nitrogen and sulfur based di‐cationic ionic liquid (IL), named 1,4‐piperazinium hydrogen sulfate ([H‐pi]HSO4), was simply synthesized from the reaction of piperazine with sulfuric acid, and then characterized with a variety of techniques, including Infrared (IR) and Nuclear Magnetic Resonance (NMR) spectroscopies, Thermo‐gravimetric analysis (TGA), Scanning Electron Microscope (SEM), and pH analysis. This new ionic liquid was employed as an efficient catalyst for the synthesis of 2,2′‐arylmethylene‐bis(3‐hydroxy‐5,5‐dimethyl‐2‐cyclohexene‐1‐one) and 1,8‐dioxooctahydroxanthene derivatives in C2H5OH:H2O media and under solvent‐free conditions, respectively. Also, this adequate catalyst was employed for the synthesis of imidazo[1,2‐a]pyrimidines and triazolo[4,3‐a]pyrimidinesviathree‐component reaction of aldehydes, malononitrile and 2‐aminobenzimidazole and/or 3‐amino[1,2,4]triazole. The new functionally‐structured products, synthesized through these methods, were characterized with IR,1H NMR,13C NMR and mass spectroscopy. Moreover, the procedures gave the products in good yields and short reaction times as well as reusability of the catalyst.

Thiazole-substituted benzoylpiperazine derivatives as acetylcholinesterase inhibitors.

Hit, Lead & Candidate Discovery After acetylcholine is released into the synaptic cleft, it is reabsorbed or deactivated by acetylcholinesterase (AChE). Studies on Alzheimer's disease (AD) in the mid-20th century proved that cognitive dysfunctions are associated with cholinergic neurotransmission. Drugs, such as tacrine, rivastigmine, donepezil, and galantamine are known as acetylcholinesterase inhibitors. However, these drugs have limited use in advanced AD and dementia. Recently, the anticholinesterase activity of various heterocyclic-framed compounds, including piperazine derivatives, has been investigated, and compounds with similar effects to known drugs have been identified. The aim of this study was to design new donepezil analogs. In this study, 66 original piperazinyl thiazole derivatives were synthesized by the reaction of piperazine N'-benzoyl thioamides and bromoacetophenones to inhibit AChE. Biological activity was measured by the Ellman method. Compounds 35, 38, 40, 45, 57, and 61 showed a high inhibitory effect among the series (80.36%-83.94% inhibition), and donepezil had a 96.42% inhibitory effect. The IC50 values of compounds 35, 38, and 40, were calculated as 0.9767 μM, 0.9493 μM, and 0.8023 μM, respectively. Compound 45 (IC50 = 1.122), Compound 57 (IC50 = 1.2130) and 61 (IC50 = 0.9193) also exhibited good activity on AChE. Molecular modeling studies were in agreement with the predictions. Trp286, Arg296, and Tyr341 were the key amino acids at the active site. Both donepezil and synthesized compounds seemed to interact with these residues.

Reactions of vinylphosphonates with piperazines

Dialkyl [2-(piperazin-1-yl)ethyl]phosphonates were obtained by the reactions of piperazine with dialkyl vinylphosphonates. The addition of 2-(piperazin-1-yl)ethanamine to diethyl vinylphosphonate involves the primary exocyclic amino group of the heterocyclic compound.

An experimental investigation into the atmospheric degradation of piperazine

The atmospheric degradation of piperazine was investigated using an indoor smog chamber. Experiments were carried out in the presence of nitrogen oxides (NOx), ozone or nitric acid. Piperazine reacted rapidly under all evaluated conditions: irradiated in the presence of NOx and with ozone and nitric acid in the dark. Gas phase products from the oxidation of piperazine were identified by infrared spectroscopy, DNPH cartridges followed by HPLC analysis, and by sampling chamber gas through Tenax sorbent material followed by analysis using thermal desorption GC-ITMS (gas chromatography ion trap mass spectrometry).Eight compounds were positively identified, with a further nine compounds tentatively identified using GC–MS based on molecular weight and mass spectra. Ammonia formation was observed from piperazine oxidation, and its formation was from the subsequent reactions of photooxidation products of piperazine rather than directly from the reaction of piperazine. The nitrosamine and nitramine expected from piperazine, N-nitrosopiperazine, and N-nitropiperazine, were both identified and confirmed using 15NO, with a tentative maximum yield of nitrosamine of less than 5% observed.Aerosol yields, relative to total piperazine reacted not including that which absorbed to the walls, were considerably high but were not able to be quantified absolutely due to unusual behaviour of the scanning mobility particle sizer instrument to aerosol containing amines. The reaction of piperazine with gas phase nitric acid gave rise to immediate formation of aerosol.

A Simplified Protocol for Routine Chemoselective Syntheses of Piperazines Substituted in the 1-Position by an Electron Withdrawing Group

We report a simplified protocol for the routine direct chemoselective preparation of various piperazines substituted in the 1-position by an electron withdrawing group. These syntheses are based on the reaction of piperazine-1- ium cation with different electrophilic reagents such as acyl chlorides, anhydrides, sulfonyl chlorides, carbamoyl chlorides, and nitrourea as well. Piperazine-1-ium cation was chosen because the reactions of piperazine with electrophilic reagents in different solvents at usual temperatures are not chemoselective and provide mixtures comprising 1- substituted, 1,4-disubstituted and unsubstituted piperazine as well. Simultaneously, the mono-protonation of piperazine is the simplest synthetic method for its protection/deprotection in comparison with the currently used mono-benzylation, mono-Boc-protection, etc. Computer modeling of acid-base equilibria for piperazine and model 1-acetylpiperazine was used as the basis for the prediction of reaction conditions suitable for the synthesis. It was found that for in situ generating of starting piperazine-1-ium cation from piperazine the application of acetic acid as reaction medium or the chemisorption of piperazine on weakly acidic cationexchanger resin were highly acceptable in terms of both reaction times and yields. The using of resin supported piperazine-1-ium cation in reaction with carboxylic anhydrides or nitrourea is an example of the solid phase synthesis with ionically bonded substrate. Furthermore, syntheses in acetic acid medium were effectively catalyzed by Cu+, Cu2+ or Al3+ ions supported on weakly acidic cation-exchanger resin as well. Finally, it was observed that application of the solid support metal catalysis afforded target products in shortened reaction times and in 82-95% yields.

An azide-bridged copper(II) complex: poly[piperazine-1,4-dium [tetra-μ₃-azido-κ¹²N¹:N¹:N¹-hexa-μ₂-azido-κ¹²N¹:N¹-di-μ₂-azido-κ⁴N¹:N³-pentacopper(II)] tetrahydrate

A new Cu(II)-azide complex, {(C4H12N2)[Cu5(N3)12]·4H2O}n, has been synthesized by the reaction of piperazine, Cu(OAc)2·2H2O (OAc is acetate) and NaN3. In the structure, μ2-1,1- and μ3-1,1,1-azide anions bridge five Cu(II) cations to form a linear pentanuclear cluster unit, which is further linked by μ2-1,1- and μ2-1,3-azide anions to form a two-dimensional condensed [Cu5(N3)12]n layer. The diprotonated piperazine and the solvent water molecules are hydrogen bonded to the coordination layers to form a three-dimensional supramolecular network.

The first bis-cyanoxime: synthesis and properties of a new versatile and accessible polydentate bifunctional building block for coordination and supramolecular chemistry

A new multidentate bifunctional organic ligand – di-N,N′-(2-cyano-2-oximinoacetyl)piperazine – was synthesized in high yield using a two-step procedure carried out under ambient conditions. At first, the reaction of piperazine and neat methylcyanoacetate led to the di-N,N′-(cyanoacetyl)piperazine (1), which then was converted into bis-cyanoxime, di-N,N′-(2-cyano-2-oximinoacetyl)piperazine (HL, 2) using a room temperature nitrosation reaction with gaseous methylnitrite. Synthesized bis-cyanoxime was characterized by 1H, 13C NMR, UV-visible, IR spectroscopy and the X-ray analysis. The ligand 2 exists as a mixture of three diastereomers arising from the syn- and anti-geometry of the cyanoxime group. The prolonged crystallization of 2 from an ethanol–water mixture leads to the formation of: (a) colorless crystals that according to the X-ray analysis contain a 51.2:48.8% co-crystallized mixture of both isomers that have the same H-bonding motif (minority), and (b) a white amorphous material that represents an almost pure anti-isomer (majority). The deprotonation of 2 leads to the formation of a yellow dianion that demonstrated pronounced solvatochromism of its n → π* transition in the nitroso-chromophore. The disodium salt Na2L·4H2O (3) was obtained from 2 using NaOC2H5 in ethanol. The new bis-cyanoxime 2 reacts with Tl2CO3 and AgNO3 in aqueous solutions with the formation of light-stable, sparingly soluble yellow precipitates of M′2L·xH2O composition (M′ = Tl, Ag; Tl = 4, x = 0; Ag = 5, x = 2). The reaction of 3 with Ni2+ or K2M′′Cl4 (M′′ = Pd, Pt) in aqueous solutions leads to NiL·4H2O (6), PdL·4H2O (7) and PtL·5H2O (8). The crystal structure of 4 was determined and revealed the formation of a 3D-coordination polymeric complex in which the bis-cyanoxime acts as a dianionic, bridging, formally decadentate ligand. Each Tl(I) center has two bonds (2.655, 2.769 Å), shorter than the sum of ionic radii Tl–O (oxime group), and three longer, >2.89 Å, mostly electrostatic Tl···O contacts, involving oxygen atoms of the amide-group and the oxime-group of neighboring units. Among several possible binding modes, the coordination of the bis-cyanoxime dianion of 2 adopted in complex 4 is unusual, and evidenced its great potential as a versatile building block for coordination and supramolecular chemistry.

First structurally characterized self-assembly of bipodal N-thiophosphorylated bis-thiourea with CoII: magnetic properties and thermal decomposition

Reaction of piperazine with isothiocyanate (iPrO)2P(S)NCS leads to N-thiophosphorylated bis-thiourea (iPrO)2P(S)NHC(S)NC4H8NC(S)NHP(S)(OiPr)2 (H2L). Recrystallization of H2L from DMSO leads to the formation of the new ligand (iPrO)2P(S)NC4H8NP(S)(OiPr)2 (1). Reaction of doubly deprotonated L with Co(II) leads to the [Co2L2] complex. The thermal properties of [Co2L2] in an air atmosphere were studied by means of TGA with the observed final residue corresponding to [CoPS3]2. The crystal structure of [Co2L2] was elucidated by single crystal X-ray diffraction. Two metal cations are in a tetrahedral 1,5-S2S'2 environment formed by the C=S and P=S sulfur atoms. Investigation of the temperature dependence of the magnetic susceptibility is consistent with two effectively non-interacting Co(II) S = 3/2 ions.

Preparation of waterborne functional polymers using a bifunctional coupler

A new piperazine based bifunctional coupler was synthesized by reaction of piperazine and epichlorohydrin in water. Functional polymers were prepared using this coupler via two different approaches: (1) by polycondensation – reacting the bifunctional coupler with a suitable diamine and (2) by post-polymerization modification – reacting the coupler or functionalized couplers with a polyamine precursor. All reactions were performed using water as a solvent in a one pot synthesis approach.

Synthesis of Phosphorylated Piperazines

Heating 3-methyl-1,2-butadienyl phosphonates with piperazine leads to the formation of 2-piperazinyl-butenyl phosphonates containing the enamine functionality. From the reaction of piperazine with four equivalents of 1,2-butadienyl phosphonate a bis(phosphonate) is obtained, in which the piperazine bridge links two phosphorylbutene fragments.

ACCELERATION OF THE WET OXIDATION REACTION OF PIPERAZINE BY HETEROGENEOUS Ru/TiO2 CATALYST

Wet air oxidation is a candidate technique for the effective treatment of wastewater contaminated by nitrogenous organic pollutants. Piperazine (PZ) is a cyclic diamine representing this class of compounds. In the present work, the wet oxidation reaction of PZ was studied for the first time. It was found that, in the studied range of temperatures of 180°–230°C and O2 partial pressures of 0.69–2.07 MPa, the oxidation process was slow. Total organic carbon (TOC) conversion at 230°C and 0.69 MPa O2 partial pressure was just 52% after 2 h. The investigated reaction was accelerated by a heterogeneous Ru/TiO2 catalyst. Maximum TOC conversion (91%) was achieved during catalytic wet oxidation at 210°C and 1.38 MPa O2 pressure. Kinetic data were collected over the range of temperatures 180°–210°C, O2 partial pressures 0.34–1.38 MPa, and catalyst loading 0.11–0.66 kg/m3. The lumped TOC concentration decay was a two-step first-order process.