Two-step syntheses of 2,4,6-triisopropylbenzenesulfonyl aziridines

In a continuing study on the α-lithiation of N-tosyl aziridines, it is reported that ortho-lithiation of the N-tosyl group is occurring under typical α-lithiation conditions (s-BuLi/PMDETA). Thus, a simple, two-step synthesis of N-2,4,6-triisopropylbenzenesulfonyl aziridines was optimised. The route involves epoxide ring opening using a sulfonamide, mesylation and base-mediated ring closure. The scope and limitations of this route were assessed and five new N-2,4,6-triisopropylbenzenesulfonyl aziridines were prepared in good yields. Since this method was unsuitable for the preparation of cyclooctene aziridine, an alternative two-step method was developed. This method involved aminobromination of cyclooctene using NBS/2,4,6-triisopropylbenzenesulfonamide.     

15N NMR spectra and reactivity of 2,4,6‐triazidopyridines, 2,4,6‐triazidopyrimidine and 2,4,6‐triazido‐s‐triazine

2,4,6‐Triazido‐s‐triazine, 2,4,6‐triazidopyrimidine and six different 2,4,6‐triazidopyridines were studied by ¹⁵N NMR spectroscopy. The assignment of signals in the spectra was performed using the gauge‐independent atomic orbital (GIAO)–Tao‐Perdew‐Staroverov‐Scuseria exchange‐correlation functional (TPSS)h/6‐311+G(d,p) calculations on the M06‐2X/6‐311+G(d,p) optimized molecular geometries. The Truhlar and coworkers' continuum solvation model called SMD was applied to treat solvent effects. With this approach, the root mean square error in estimations of the ¹⁵N chemical shifts for the azido groups was just 1.9 ppm. It was shown that the different reactivity of the α‐ and γ‐azido groups in pyridines correlates well with the chemical shifts of the N_α signals of these groups. Of two nonequivalent azido groups of azines, the azido group with the most shielded N_α signal is the most electron‐deficient and reactive toward electron‐rich reagents. By contrast, the azido group of azines with the most deshielded N_α signal is the most reactive toward electron‐poor reagents. Copyright © 2013 John Wiley & Sons, Ltd.     

Polarographic reduction of 2,4,6-trinitrobenzene-1-sulphonic acid and some 2,4,6-trinitrophenyl-amino acid derivatives

The rapid d.c. polarography of 2,4,6-trinitrobenzene-1-sulphonic acid and its derivatives with serine (I), threonine (II), glycine (III) and histidine (IV) revealed a 3-wave reduction and a marked pH dependence of the reduction potential. The polarographic waves of the derivatives (2.5 × 10^?4 M) showed appreciable changes when sulphite ions were present, with the development of a new wave at more negative potential in ?0.01 M sulphite solutions at pH 7.0. The E_1/2 values of these waves in pH 7.0 supporting electrolyte were: (I) ?1000; (II) ?1007; (III) ?1021; (IV) ?949 mV (vs. Ag/AgCl, sat. KCl). These waves were used to determine the amino acids investigated (1–4 × 10^?4 M) in the presence of excess of 2,4,6-trinitrobenzene-1-sulphonic acid, with good precision (2%).     

Mass spectrometric properties of N‐(2‐methoxybenzyl)‐2‐(2,4,6‐trimethoxyphenyl)ethanamine (2,4,6‐TMPEA‐NBOMe), a new representative of designer drugs of NBOMe series and derivatives thereof

Emergence of new psychoactive substances, hallucinogenic phenethylamines in particular, in illicit market is a serious threat to human health in global scale. We have detected and identified N‐(2‐methoxybenzyl)‐2‐(2,4,6‐trimethoxyphenyl)ethanamine (2,4,6‐TMPEA‐NBOMe), a new compound in NBOMe series. Identification was achieved by means of gas chromatography/mass spectrometry (GC/MS), including high‐resolution mass spectrometry with tandem experiments (GC/HRMS and GC/HRMS²), ultra‐high performance liquid chromatography/high‐resolution mass spectrometry with tandem experiments (UHPLC/HRMS and UHPLC/HRMS²), and ¹H and ¹³C nuclear magnetic resonance spectroscopy. The peculiarities of fragmentation of the compound under electron ionization (EI) and collision‐induced dissociation were studied. Despite of the empirical rule denying migration of the hydrogen atom in McLafferty rearrangement to the benzene ring with substituents in the both ortho‐positions, it easily occurs for 2,4,6‐TMPEA‐NBOMe in EI conditions. We have noticed that electron‐donating substituents, e.g. methoxy groups in the both ortho‐positions and para‐positions favor the rearrangement. For specially synthesized N‐methyl and N‐acyl derivatives McLafferty rearrangement is not observed. N‐Acyl derivatives demonstrate McLafferty rearrangement, but the charge retains at the alternative fragment involving N‐acyl carbonyl group. We have also showed that the hydrogen atoms in 2,4,6‐trimethoxybenzene ring may be easily substituted for deuterium or for strong electrophiles like trifluoroacetyl. Analytical characteristics of 2,4,6‐TMPEA‐NBOMe and of some derivatives thereof which enable their determination in various criminal seizures are given. Copyright © 2016 John Wiley & Sons, Ltd.     

Effects of synthesis-solvent on swelling and elastic properties of poly(N-isopropylacrylamide) hydrogels

Thermosensitive N-isopropylacrylamide (NIPA) hydrogels were synthesized by a free radical copolymerization with N,N′-methylenebisacrylamide (MBAA) in four solvents: water, ethanol, acetone and N,N-dimethylformamide. The swelling and elastic properties of the hydrogels were affected by the synthesis-solvents; the hydrogels (e.g. NIPA/MBAA = 1000/50 mol/m³-pre-gel solution) synthesized in water have smaller swelling volume and larger shear modulus at 10 °C than those synthesized in amphiphilic solvents. The network structure of hydrogels was estimated in terms of the conversion and two sorts of effective crosslinking density based on the Flory theory and the concentration of crosslinker. The hydrogels synthesized in water can have the microscopic inhomogeneous network arising from the entanglement of polymer chains, while the hydrogels synthesized in amphiphilic solvents can have the homogeneous network arising from the polymer concentration lower than the pre-gel solution and can be similar in network structure to the lightly crosslinked hydrogel synthesized in water.     

Thermochemical studies of sym-dichlorobis (2,4,6-trichlorophenyl) urea

Thermal decomposition of sym-dichlorobis (2,4,6-trichlorophenyl) urea occurs by two steps: the first at 150–184°C accompanied by a 26% weight loss and +(16.6±0.7) kcal mole^?1 and the second by a 40% weight loss and ?(17.4±1.0) kcal mole^?1. The decomposition pressure follows the equation ln p=A + B/T + C/T² where A = 149.89, B=9.45·10 [4] and C=1.48·10 [7]. The decomposition products are 2,4,6-trichlorophenyl isocyanate 2,4,6-trichloroaniline, chlorine, 1,2,3,5-tetrachlorobenzene, 2,2′,4,4′,6,6′-hexachlorobiphenyl, 2,2′,4,4′-tetrachlorobiphenyl, 2,2′,4,4′,6-pentachlorobiphenyl and ammonium chloride.     

Antigen Responsive Hydrogels Based on Polymerizable Antibody Fab′ Fragment

Novel antigen responsive hydrogels were prepared by using polymerizable antibody Fab′ fragment from monoclonal anti‐fluorescein BDC1 antibody (IgG2a). To form Fab′ containing hydrogels, the polymerizable Fab′ fragment was copolymerized with N‐isopropylacrylamide (NIPAAm) and N,N′‐methylenebis(acrylamide) (MBAAm; crosslinker) using redox initiators. The thermosensitivity of the hydrogels decreased with increasing Fab′ fragment content. The antigen responsiveness of the hydrogels depended on the Fab′ content, pH, and temperature. When the hydrogels were alternately exposed to antigens fluorescein (FL) and polyamidoamine dendrimer (PAMAM)‐fluorescein (FD), significant reversible volume changes were observed for the hydrogel containing 50% (w/w) Fab′ fragment at 33.7 and 36.8 °C in acetate buffer (10 mM , pH 5.0), respectively, but not at 27.7 °C or in PBS buffer (10 mM , pH 7.4). No noticeable reversible volume changes were observed with pure PNIPAAm hydrogel and the gel containing 10% (w/w) Fab′ fragment.

Structure of Fab′ containing hydrogels.     

Supramolecular interactions in some organic hydrated 2,4,6-triaminopyrimidinium carboxylate and sulfate salts

Four salts, namely, 2,4,6-triaminopyrimidinium 6-chloronicotinate dihydrate, C₄H₈N₅⁺·C₆H₃ClNO₂⁻·2H₂O, (I), 2,4,6-triaminopyrimidinediium pyridine-2,6-dicarboxylate dihydrate, C₄H₉N₅²⁺·C₇H₃NO₄²⁻·2H₂O, (II), 2,4,6-triaminopyrimidinediium sulfate monohydrate, C₄H₉N₅²⁺·SO₄²⁻·H₂O, (III), and 2,4,6-triaminopyrimidinium 3,5-dinitrobenzoate dihydrate, C₄H₈N₅⁺·C₇H₃N₂O₆⁻·2H₂O, (IV), were synthesized and characterized by X-ray diffraction techniques. Proton transfer from the corresponding acid to the pyrimidine base has occurred in all four crystal structures. Of the four salts, two [(I) and (IV)] exist as monoprotonated bases and two [(II) and (III)] exist as diprotonated bases. In all four crystal structures, the acid interacts with the pyrimidine base through N—H…O hydrogen bonds, generating an R₂²(8) ring motif. The sulfate group mimics the role of the carboxylate anions. The water molecules present in compounds (I)–(IV) form water-mediated large ring motifs. The formation of water-mediated interactions in these crystal structures can be used as a model in the study of the hydration of nucleobases. Water molecules play an important role in building supramolecular structures. In addition to these strong hydrogen-bonding interactions, some of the crystal structures are further enriched by aromatic π–π stacking interactions [(I) and (II)].     

The synthesis and characterization of 2,4,6-tris(3,4-dihydroxybenzimino)-1,3,5-triazine and its [salen/salophenFe(III)] and [salen/salophenCr(III)] capped complexes

Four new trinuclear Fe(III) and Cr(III) complexes involving tetradentate Schiff bases N,N′-bis(salicylidene)ethylenediamine-(salenH₂) or bis(salicylidene)-o-phenylenediamine-(salophenH₂) with 2,4,6-tris(3,4-dihydroxybenzimino)-1,3,5-triazine have been synthesized and characterized by means of elemental analysis, ¹H N.M.R., FT-IR spectroscopy, thermal analyses and magnetic susceptibility measurements. The complexes have also been characterized as low-spin distorted octahedral Fe(III) and Cr(III) bridged by catechol group.     

Thermo- and pH-sensitive comb-type grafted poly(N,N-diethylacrylamide-co-acrylic acid) hydrogels with rapid response behaviors

Poly(N,N-diethylacrylamide) with a terminal hydroxyl end group (PDEA-OH) was synthesized by radical telomerization of N,N-diethylacrylamide (DEA) monomer using 2-hydroxyethanethiol as a chain transfer agent. Macromonomer of thermo-sensitive PDEA was synthesized by condensation reaction of PDEA-OH with acryloyl chloride. The macromonomer was characterized by FTIR and ¹H NMR, and the molecular weight was determined by GPC. Thermo- and pH-sensitive comb-type grafted poly(N,N-diethylacrylamide-co-acrylic acid) (PDEA-co-AA) hydrogels (GHs) were successfully prepared by grafting PDEA chains with freely mobile ends onto the backbone of a cross-linked (PDEA-co-AA) network. The results showed that the deswelling behavior of the hydrogels was dependent on the test temperature. At 45 °C (beneath the VPTT of the hydrogels), both the normal-type hydrogels (NHs) and comb-type grafted P(DEA-co-AA) hydrogels had lower deswelling rates. While at 60 °C (far beyond the VPTT of the hydrogels), the deswelling rates of the GHs were faster than that of the NHs. Furthermore, pulsatile stimuli-responsive studies indicated that the GHs had excellent thermo-reversibility and were superior to the NHs in the magnitude of their swelling ratios to temperature changes. However, the reversibility to pH changes was poor for both the NHs and the GHs.     

Synthesis, characterisation and evaluation of poly[lactose acrylate-N-vinyl-2-pyrrolidinone] hydrogels for drug delivery

New biodegradable polymeric hydrogels based on biocompatible materials, lactose acrylate (LA) and N-vinyl-2-pyrrolidinone were designed and synthesized. LA was synthesized and characterized by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. Hydrogel synthesis was carried out by free-radical polymerization of the co-monomers using azobisisobutyronitrile as initiator and N,N^′-methylenebisacrylamide as crosslinker. These hydrogels were also characterized. Equilibrium swelling of the hydrogels was studied in phosphate buffer of physiological pH, 7.4 and at 37 °C. Propranolol hydrochloride was entrapped into these hydrogels and the in vitro release profile of this drug was established in phosphate buffer. The drug release followed a near zero-order fashion in the first 6 h and thereafter slowed down releasing more than 90% of the entrapped drug at the end of 48 h.     

The powder X-band electron paramagnetic resonance spectroscopy of septet pyridyl-2,4,6-trinitrene

The first X-band EPR spectrum containing only non-overlapping signals of septet pyridyl-2,4,6-trinitrene and triplet pyridylnitrenes is reported. This spectrum was recorded after photolysis of 2,4,6-triazidopyridine in solid argon at 5 K. The zero-field splitting (ZFS) parameters of this trinitrene as well as of intermediate triplet mononitrenes and quintet dinitrenes formed at early stages of the photolysis were determined using the combination of modern computer line-shape spectral simulations and density functional theory (DFT) calculations. It was found that septet pyridyl-2,4,6-trinitrene has the record negative parameter D_S = −0.1031 cm⁻¹ among all known to date septet pyridyl-2,4,6-trinitrenes and may be of interest as a model multi-qubit spin system for investigations of quantum computation processing.     

Darstellung und eigenschaften von 124,2,4,6-thiatriazin-1-oxiden. zur struktur der hydrolyseprodukte von 1-arensulfonyl-imino-1λ4,2,4,6-thiatriazinen

Synthesis and structure of 4-phenoxy-H[1λ⁴,2,4,6]thiatriazino[4,3a]benzimidazole-2-oxide 5, 3-amino-4H[1λ⁴,2,4,6]thiatriazino[2,3-a]benzimidazole-1-oxide 6 and 3-amino-5-dimethylamino-2-tosyl-1λ⁴, 2,4,6-thiatriazine-1-oxide 7, obtained by hydrolysis of the corresponding arenesulfonyl imino compounds are discussed. The molecular and crystal structure of N-benzoyl-? tosyl-guanidine is presented.     

Synthesis and characterization of poly(methacrylic acid) hydrogels for metoclopramide delivery

Polymeric hydrogels based on biocompatible materials, methacrylic acid (MAA), were designed and synthesized. Synthesis was carried out by free-radical copolymerization using potassium persulfate as initiator and N,N^′-methylenebisacrylamide as crosslinker. Hydrogels were also characterized by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance spectroscopy (¹H NMR) and differential scanning calorimetry (DSC). DSC was used for the quantitive determination of the amounts of freezing and non-freezing water of the hydrogels with 0.5% of N,N^′-methylenebisacrylamide. Equilibrium swelling of hydrogels was studied in phosphate buffer of physiological pH (1.0, 4.0, 7.4 and 8.5) at 37 °C. The swelling kinetic of the hydrogels were studied and the kinetic characteristic constant of copolymeric systems, k, and the exponent which characterizes the mechanism of water transport at short times, n, were obtained. Metoclopramide hydrochloride was entrapped into the hydrogels by sorption and the “in vitro” release profile of this drug was established in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). It was observed that the drug release mechanism was non-Fickian.     

Synthesis and crystal structures of 2,4,6-pyridine-tricarboxylic anions/guanidinium and tetraalkylammonium inclusion compounds

Two different hydrogen-bonded inclusion compounds, [2,4,6-C₅H₂N(COO^?)₃]_0.5·[C(NH₂) ₃ ⁺ ]_0.5·[(C₂H₅)₄N⁺]·2H₂O (1) and [2,4,6-C₅H₂N(COO^?)₃]·[C(NH₂) ₃ ⁺ ]·[(C₂H₅)₄N⁺]·[(C₃H₇)₄N⁺]·6H₂O (2) are reported in this paper, in which 2,4,6-pyridine-tricarboxylic anions, guanidiniums and water molecules jointly construct host lattices while tetraalkylammonium cations are accommodated as guest species. Both two compounds formed sandwich-like hydrogen-bond inclusion compounds. In compound 1, the dimers composed of 2,4,6-pyridine-tricarboxylic anions and guanidiniums form 2D hydrogen-bonded layers by connecting with water molecules. In compound 2, 2,4,6-pyridine-tricarboxylic anions, guanidiniums and water molecules contribute to generate an undulate rosette hydrogen-bonded architecture. Interestingly, in compound 2, there are two species of guest molecules, tetraethylammonium and tetrapropylammonium, which are alternately arranged between the neighboring layers. Mixed guest cations accommodated in hydrogen-bonded inclusion compounds are seldom seen.     

Magnetic anisotropy parameters of matrix-isolated septet 1,3,5-trinitreno-2,4,6-trichlorobenzene

An ESR spectrum of high-symmetry septet 1,3,5-trinitreno-2,4,6-trichlorobenzene generated under photolysis of 1,3,5-triazido-2,4,6-trichlorobenzene in solid argon at 15 K was recorded. Computer simulation revealed that the spectrum corresponds to the septet spin state with the fine structure parameters D _S = ?0.0957±0.0006 cm^?1 and E _S = 0±0.0004 cm^?1. These values of the magnetic anisotropy parameters D _S and E _S are in good agreement with the results of UDFT calculations. The spin-spin (D _SS) and spin-orbit (D _SO) coupling parameters of septet molecules with D _3h symmetry are negative and mutually enhance the magnetic anisotropy of these molecules. The contribution of the spin-orbit coupling to the magnetic anisotropy of 1,3,5-trinitreno-2,4,6-trichlorobenzene is higher than 11% due to the presence of three chlorine atoms in the molecule. This suggests the possibility of further strengthening the magnetic properties of septet 1,3,5-trinitrenobenzenes by introducing bromine and iodine atoms into positions 2, 4, and 6 of their benzene rings.     

Ring transformations of heterocyclic compounds. XIII. Bis(2,4,6-triarylphenyl) substituted bispyridinium salts from methyl derivatives by double pyrylium and thiopyrylium ring transformations

The synthesis of hitherto unknown 4,4′-bis(2,4,6-triarylphenyl) substituted bispyridinium diperchlorates 3 , in which the N-atoms are linked by a carbon chain, a heteroatom containing a carbon chain or a bis(methylene) substituted aromatic/heteroaromatic ring, from 4,4′-dimethylbispyridinium derivatives 2 by a double 2,6-[C₅+C] ring transformation of 2,4,6-triarylpyrylium and 2,4,6-triarylthiopyrylium salts 1/4 is reported. Spectroscopic data of the bispyridinium diperchlorates 3 and their mode of formation are discussed.     

Swelling behavior of strong polyelectrolyte poly(N-t-butylacrylamide-co-acrylamide) hydrogels

Temperature-sensitive ionic hydrogels based on N-t-butylacrylamide (TBA), acrylamide (AAm), 2-acrylamido-2-methylpropane sulfonic acid sodium salt (AMPS) and N,N^′-methylenebis(acrylamide) (BAAm) monomers were prepared. The molar ratio of TBA to the monomers AAm and AMPS was fixed at 60/40, while the AMPS content of the hydrogels was varied. The elastic modulus of the hydrogels was in the range of 347-447 Pa, much lower than the modulus of PAAm or poly(N-isopropylacrylamide) hydrogels due to the reduced crosslinking efficiency of BAAm in TBA/AAm copolymerization. The hydrogels exhibited swelling-deswelling transition in water depending on the temperature. Increasing ionic group (AMPS) content resulted in shifting of the transition temperature interval in which the deswelling takes place. The higher the ionic group content, the broader the temperature interval at the phase transition. Ionic hydrogels exhibited first-order reentrant conformational transitions in ethanol-water and in dimethylsulfoxide (DMSO)-water mixtures. The higher the ionic group content of the hydrogels the narrower the ethanol (or DMSO) range in which the reentrant phenomena occur. By taking into account the difference of the solvent mixture composition inside and outside the gel, the equilibrium swelling theory provided a satisfactory agreement to the experimental swelling data of the hydrogels immersed in the solvent mixtures.     

N,N-Dichlorobis(2,4,6-trichlorophenyl)urea (CC-2) as a new reagent for the synthesis of pyrimidone and pyrimidine derivatives via Biginelli reaction

A simple and efficient method for the synthesis of 3,4-dihydropyrimidin-2-(1H)one and benzo[4,5]imidazo/thioazo[1,2-a]pyrimidine derivatives has been described using N,N′-dichlorobis(2,4,6-trichlorophenyl)urea (CC-2) as a new reagent. This method is found to be efficient and convenient for the synthesis of pyrimidone and pyrimidine derivatives.     

Synthesis and characterization of 1,3,5-tris((1/2<Emphasis Type="Italic">H</Emphasis>-tetrazol-5-yl)methyl)-1,3,5-triazinane-2,4,6-trione

2,2′,2″-(2,4,6-Trioxo-1,3,5-triazinane-1,3,5-triyl) triacetonitrile (or tris-(cyanomethyl)-isocyanurate) and 1,3,5-tris((1/2H-tetrazol-5-yl)methyl)-1,3,5-triazinane-2,4,6-trione (or tris-(5-tetrazolylmethyl)-isocyanurate) were synthesized with new methods. High yields, simple methodology, and cheapness are advantages of the methods. Furthermore, 1,3,5-tris((1/2H-tetrazol-5-yl)methyl)-1,3,5-triazinane-2,4,6-trione was synthesized in the less hazardous condition. The compounds were characterized by elemental analysis, IR, ¹HNMR, ¹³CNMR and mass spectroscopic analysis. In addition, DSC/TGA measurements were carried out to determine the thermal behavior of the final product.