ABSTRACT
We reported a novel simplified synthetic procedure for the preparation of monosubstituted piperazine derivatives which can now be easily prepared in a one-pot-one-step way from a protonated piperazine with no need of introduction of a protecting group. Reactions, proceeding either at room or higher temperatures in common solvents, involve heterogeneous catalysis by metal ions supported on commercial polymeric resins. A general synthetic scheme was successfully applied to afford a wide range of monosubstituted piperazines. Furthermore, we picked up a set of piperazine derivatives and studied the possibilities of microwave acceleration of given synthetic reactions to make them even more efficient. Our research proceeded from a simple batch technique to the construction of a flow microwave reactor prototype and resulted in promising findings which are summarized and discussed in the article.
Subject(s)
Microwaves , Piperazines/chemical synthesis , Solvents/chemistry , Catalysis , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/chemistry , Piperazines/chemistryABSTRACT
A series of 1,3,5-triazine analogues, incorporating aminobenzene sulfonamide, aminoalcohol/phenol, piperazine, chalcone, or stilbene structural motifs, were evaluated as potential antioxidants. The compounds were prepared by using step-by-step nucleophilic substitution of chlorine atoms in starting 2,4,6-trichloro-1,3,5-triazine. Reactions were catalyzed by Cu(I)-supported on a weakly acidic resin. The radical scavenging activity was determined in terms of %inhibition activity and EC50, using the ABTS method. Trolox and ascorbic acid (ASA) were used as standards. In the lowest concentration 1 × 10-4 M, the %inhibition activity values at 0 min were comparable with both standards at least for 10 compounds. After 60 min, compounds 5, 6, 13, and 25 showed nearly twice %inhibition (73.44-87.09%) in comparison with the standards (Trolox = 41.49%; ASA = 31.07%). Values of EC50 at 60 min (17.16-27.78 µM) were 5 times lower for compounds 5, 6, 13, and 25 than EC50 of both standards (trolox = 178.33 µM; ASA = 147.47 µM). Values of EC50 correlated with %inhibition activity. Based on these results, the presented 1,3,5-triazine analogues have a high potential in the treatment of illnesses caused or related to oxidative stress.
Subject(s)
Antioxidants/chemistry , Antioxidants/pharmacology , Chalcone/chemistry , Phenol/chemistry , Piperazine/chemistry , Sulfonamides/chemistry , Triazines/chemistry , Triazines/pharmacology , Antioxidants/chemical synthesis , Chemistry Techniques, Synthetic , Molecular Structure , Structure-Activity Relationship , Triazines/chemical synthesisABSTRACT
An efficient and simple methodology for Ullmann Cu(I)-catalyzed synthesis of di- and trisubstituted 1,3,5-triazine derivatives from dichlorotriazinyl benzenesulfonamide and corresponding nucleophiles is reported. Cations Cu(I) supported on macroporous and weakly acidic, low-cost industrial resin of polyacrylate type were used as a catalyst. The reaction times and yields were compared with traditional synthetic methods for synthesis of substituted 1,3,5-triazine derivatives via nucleophilic substitution of chlorine atoms in dichlorotriazinyl benzenesulfonamide. It was found that Ullmann-type reactions provide significantly shortened reaction times and, in some cases, also higher yields. Finally, trisubstituted s-triazine derivatives were effectively prepared via Ullmann-type reaction in a one-pot synthetic design. Six new s-triazine derivatives with potential biological activity were prepared and characterized.
Subject(s)
Copper/chemistry , Triazines/chemical synthesis , Catalysis , Molecular Structure , Porosity , Triazines/chemistryABSTRACT
The formation of W x O y+â/-â clusters in the gas phase was studied by laser desorption ionization (LDI) and matrix assisted laser desorption ionization (MALDI) of solid WO3. LDI produced (WO3) n+ â/- â (n = 1-7) clusters. In MALDI, when using nano-diamonds (NDs), graphene oxide (GO), or fullerene (C60) matrices, higher mass clusters were generated. In addition to (WO3) n-â clusters, oxygen-rich or -deficient species were found in both LDI and MALDI (with the total number of clusters exceeding one hundred ≈ 137). This is the first time that such matrices have been used for the generation of(WO3) n+â/-â clusters in the gas phase, while new high mass clusters (WO3) n-â (n = 12-19) were also detected. Graphical Abstract.
ABSTRACT
A new series of s-triazine derivatives incorporating sulfanilamide, homosulfanilamide, 4-aminoethyl-benzenesulfonamide and piperazine or aminoalcohol structural motifs is reported. Molecular docking was exploited to select compounds from virtual combinatorial library for synthesis and subsequent biological evaluation. The compounds were prepared by using step by step nucleophilic substitution of chlorine atoms from cyanuric chloride (2,4,6-trichloro-1,3,5-triazine). The compounds were tested as inhibitors of physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms. Specifically, against the cytosolic hCA I, II and tumor-associated hCA IX. These compounds show appreciable inhibition. hCA I was inhibited with KIs in the range of 8.5-2679.1â¯nM, hCA II with KIs in the range of 4.8-380.5â¯nM and hCA IX with KIs in the range of 0.4-307.7â¯nM. As other similar derivatives, some of the compounds showed good or excellent selectivity ratios for inhibiting hCA IX over hCA II, of 3.5-18.5. 4-[({4-Chloro-6-[(4-hydroxyphenyl)amino]-1,3,5-triazin-2-yl}amino)methyl] benzene sulfonamide demonstrated subnanomolar affinity for hCA IX (0.4â¯nM) and selectivity (18.50) over the cytosolic isoforms. This series of compounds may be of interest for the development of new, unconventional anticancer drugs targeting hypoxia-induced CA isoforms such as CA IX.
Subject(s)
Amino Alcohols/pharmacology , Carbonic Anhydrase Inhibitors/pharmacology , Piperazine/pharmacology , Sulfonamides/pharmacology , Triazines/pharmacology , Amino Alcohols/chemistry , Antigens, Neoplasm/metabolism , Carbonic Anhydrase I/antagonists & inhibitors , Carbonic Anhydrase I/metabolism , Carbonic Anhydrase II/antagonists & inhibitors , Carbonic Anhydrase II/metabolism , Carbonic Anhydrase IX/antagonists & inhibitors , Carbonic Anhydrase IX/metabolism , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrase Inhibitors/chemistry , Dose-Response Relationship, Drug , Humans , Molecular Structure , Piperazine/chemistry , Structure-Activity Relationship , Sulfonamides/chemistry , Triazines/chemistryABSTRACT
A series of ether phosphonates have been prepared by trichloroacetimidate and acetate coupling methods. Trichloroacetimidates or acetates were treated with primary and secondary alcohols as O-nucleophiles in the presence of catalytic TMSOTf to afford 21 examples of diethyl alkyloxy(substitutedphenyl)methyl phosphonates via C-O bond formation in 55-90% yields and short reaction time.
ABSTRACT
In this paper, we introduce a novel and convenient method for the transformation of heterocyclic amides into heteocyclic thioamides. A two-step approach was applied for this transformation: Firstly, we applied a chlorination of the heterocyclic amides to afford the corresponding chloroheterocycles. Secondly, the chloroherocycles and N-cyclohexyl dithiocarbamate cyclohexylammonium salt were heated in chloroform for 12 h at 61 °C to afford heteocyclic thioamides in excellent yields.
ABSTRACT
A method for preparation of a new stable Cu(I) catalyst supported on weakly acidic polyacrylate resin without additional stabilizing ligands is described. A simple and efficient methodology for Ullmann Cu(I) catalyzed C-N cross coupling reactions using this original catalyst is reported. Coupling reactions of 4-chloropyridinium chloride with anilines containing electron donating (EDG) or electron withdrawing (EWG) groups, naphthalen-2-amine and piperazine, respectively, are successfully demonstrated.
Subject(s)
Acrylic Resins/chemistry , Aniline Compounds/chemistry , Copper/chemistry , Electrons , Pyridinium Compounds/chemical synthesis , 2-Naphthylamine/chemistry , Catalysis , Equipment Reuse , Green Chemistry Technology , Hydrogen-Ion Concentration , Piperazine , Piperazines/chemistryABSTRACT
We report the vibrational spectral analysis was carried out using FT-IR and FT-Raman spectroscopy for 1-(pyrid-4-yl)piperazine (PyPi). Single crystals of PyPi suitable for X-ray structural analysis were obtained. The acid-base properties are also reported. PyPi supported on a weak acid cation-exchanger in the single protonated form and this system can be used efficiently as the solid supported analogue of 4-N,N-dimethyl-aminopyridine. The complete vibrational assignments of wavenumbers were made on the basis of potential energy distribution. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule and with the molecular electrostatic potential map was applied for the reactivity assessment of PyPi molecule toward proton, electrophiles and nucleopholes as well. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. The calculated first hyperpolarizability of PyPi is 17.46 times that of urea.
Subject(s)
Acids/chemistry , Alkalies/chemistry , Models, Molecular , Piperazines/chemistry , Pyridines/chemistry , Spectrum Analysis, Raman , Amines/chemistry , Molecular Conformation , Piperazine , Protons , Spectroscopy, Fourier Transform Infrared , Static Electricity , Thermodynamics , VibrationABSTRACT
The infrared and Raman spectra of (E)-4-((anthracen-9-ylmethylene)amino)-N-carbamimidoylbenzene sulfonamide have been recorded and analysed. Geometry and harmonic vibrational wavenumbers were calculated theoretically using Gaussian03 set of quantum chemistry codes. The data obtained from vibrational wavenumber calculations are used to assign vibrational bands found in infrared and Raman spectra of the studied molecule. The red-shift of the NH stretching band in the infrared spectrum from the computed wavenumber indicates the weakening of the NH bond. The NH stretching band has split into a doublet in the IR spectrum owing to the Davydov coupling between neighbouring units. The geometrical parameters of the title compound are in agreement with the reported similar derivatives. The calculated first hyperpolarizability is comparable with the reported value of similar structures and may be an attractive object for further studies on non-linear optics. The important thermodynamical parameters are also reported.
Subject(s)
Anthracenes/chemistry , Computer Simulation , Spectrophotometry, Infrared , Spectroscopy, Fourier Transform Infrared , Spectrum Analysis, Raman , Sulfonamides/chemistry , Models, Molecular , Molecular StructureABSTRACT
New analogs of indole phytoalexin 1-methoxyspirobrassinol methyl ether have been designed by replacement of its 2-methoxy group with 2-(substituted phenyl)amino group. Synthesized by spirocyclization methodology, trans- and cis-diastereoisomers of target compounds were isolated and evaluated as potential anticancer and antimicrobial agents. Their molecular geometries were refined by ab initio minimizations. Pharmacophore modeling and QSAR studies were performed in order to correlate their molecular structure and biological activity.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/toxicity , Indoles/chemical synthesis , Indoles/toxicity , Antineoplastic Agents/chemistry , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Indoles/chemistry , Models, Chemical , Quantitative Structure-Activity Relationship , Sesquiterpenes , Stereoisomerism , Terpenes/chemical synthesis , Terpenes/chemistry , PhytoalexinsABSTRACT
FT-Raman and FT-IR spectra of 2-cyanophenylisocyanid dichloride were recorded and analyzed. The vibrational frequencies of the title compound have been computed using the Hartree-Fock/6-31G* basis and compared with the experimental values. The prepared compound was identified by NMR and mass spectra.