New insights into bromination process: effective preparation of Ambroxol

Ambroxol used as an expectorant in treating respiratory diseases was effectively prepared with a total yield of 62%, with o-toluidine as the feedstock via successive procedures of electrophilic bromination, acetylation, radical benzylic bromination, N-alkylation and hydrolysis processes. The addition of aqueous hydrogen peroxide could enhance the utilisation of liquid bromine in the electrophilic bromination of o-toluidine, avoiding the hazardous HBr generated as a by-product. In addition, liquid bromine promoted by MnO₂ was used efficiently for the radical benzylic bromination of N-acetyl-N-(2,4-dibromo-6-methylphenyl)acetamide under mild conditions.     

Synthesis and structure of tri(<Emphasis Type="Italic">o</Emphasis>-tolyl) antimony dioximates

Tri(o-tolyl) antimony dioximates were synthesized by the reaction of tri(o-tolyl) antimony with 5-nitrofurfural and thiophen-2-carbaldehyde oximes in ether in the presence of hydrogen peroxide or tert-butylhydroperoxide (1: 2: 1 mol). Antimony atoms in the reaction products have distorted trigonal-bipyramidal coordination with the intramolecular distances Sb···N shorter than the sum of the van der Waals radii of Sb and N by ~1 Å.     

FT-IR study of the properties of water in Triton N-42 inverse micelles

The distribution of free (bulk) and bound (hydration) water in Triton N-42 inverse micelles has been studied. The percent of bulk water changes from 12% to 27% when solubilization capacity* (V _s /V _o ) increases from 0.5 vol.% to 3.5 vol.%. Triton N-42 inverse micelles contain hydration water of two types: 1) water bound with hydroxyl groups and secondary-bound with ethoxy groups and 2) water primary-bound with ethoxy groups. The quantity of water of each type is calculated as a function of solubilization capacity. The polar group of the surfactant molecule is hydrated by approximately six H₂O molecules when V _s /V _o = 3.5 vol.%.     

Formation of solvate structures by the <Emphasis Type="Italic">ortho</Emphasis>-, <Emphasis Type="Italic">meta</Emphasis>-, and <Emphasis Type="Italic">para</Emphasis>-isomers of hydroxybenzoic acid in supercritical fluid

The solvate structures formed by the ortho-, meta-, and para-isomers of hydroxybenzoic acid (o-HBA, m-HBA, and p-HBA) with a polar co-solvent (methanol at a concentration of 0.030 and 0.035 mole fractions) in supercritical carbon dioxide at a constant density of 0.7 g/cm³ and temperatures of 318 and 328 K have been studied by the classic molecular dynamics. It has been determined that a stable hydrogen-bonded complex with the co-solvent forms via the hydrogen of the carboxyl group for all isomers. The probability of this complex existence is high at all temperatures and concentrations. In the o-HBA molecule, the other functional groups are engaged in the intramolecular hydrogen bond, but not involved in interactions with methanol. It has been found that m-HBA and p-HBA can be involved in hydrogen bonds with methanol via hydroxyl hydrogen and oxygen atoms; they are characterized by the presence of one more co-solvent molecule (rarely, two molecules) in their solvation shell and intermittent formations/breakages of hydrogen bonds via other functional groups. These bonds are far less stable, and their formation is sensitive to change of temperature and co-solvent concentration. It has been concluded that the degree of selective solvation of m-HBA and p-HBA by co-solvent molecules is approximately the same, but the rate of structural rearrangements in the nearest environment of m-HBA is higher than that of p-HBA.     

IR spectra and structure of poly(vinylamide) complexes with hydrogen peroxide

The IR spectra of anhydrous thin films of hydrogen peroxide complexes with cyclic and aliphatic poly(N-vinylamides) have been studied. Splitting of a band due to stretching vibrations of C=O groups in the IR spectra of the poly(vinylcaprolactam) complex is accounted for by the resonance interaction of v _C=O vibrations of two monomer units linked by a hydrogen peroxide molecule. The formation of a N-H···O=C intramolecular hydrogen bond between neighboring polymer units is responsible for the observed low absorption of hydrogen peroxide by N-vinylamide polymers and copolymers. The energy E _H of hydrogen bonds formed between hydrogen peroxide and polymer chain fragments has been estimated by quantum-mechanical calculations. Depending on the complex structure, the value of E _H varies from 13 to 29 kJ/mol.     

Enzyme responsive supramolecular hydrogels assembled from nonionic peptide amphiphiles

Smart peptide hydrogels are of great interest for their great potential applications. Here, we report a facile approach to prepare a class of enzyme-responsive hydrogels in a scalable manner. These hydrogels self-assemble from a family of nonionic peptide amphiphiles(PAs) synthesized by sequential ring-opening polymerization(ROP) of γ-benzyl-L-glutamate N-carboxyanhydride(BLG-NCA) and L-tyrosine N-carboxyanhydride(Tyr-NCA), followed by subsequent aminolysis. These PA samples can readily form a clear hydrogel with a critical gelation concentration as low as 0.5 wt%. The incorporation of tyrosine residues offers hydrophobicity, hydrogen-bonding interaction and enzyme-responsive properties. The hydrogel-to-nanogel transition is observed under physiological conditions in the presence of horseradish peroxidase(HRP) and hydrogen peroxide(H2 O2). The obtained PA hydrogels are ideal candidates for the new generation of smart scaffolds.     

Synthesis and structure of bis(1,2-diaminoethane) copper(II) bis(<Emphasis Type="Italic">o</Emphasis>-hydroxybenzoate) monohydrate and <Emphasis Type="Italic">trans</Emphasis>-diaquabis(1,2-diaminoethane)copper(II) bis(<Emphasis Type="Italic">o</Emphasis>-aminobenzoate)

X-ray structural analysis has been performed for two complex compounds: Cu(en)₂(o-HB)₂H₂O (I) (a = 16.873(4) Å, b = 8.713(2) Å, c = 14.803(3) Å, β = 91.15(2)°, V = 2175.8(8) ų, C2/c, Z = 4, R(F) = 0.0263, 1516 reflections with I > 3σ (I)) and [Cu(en)₂(OH₂)₂]²⁺(o-AB^?)₂ (II) (a = 7.488(5) Å, b = 22.122(8) Å, c = 7.856(5) Å, β = 118.77(2)°, V = 1140.7(11) ų, P2₁/n, Z = 2, R(F) = 0.0432, 1684 reflections with I > 3σ(I)) synthesized under identical conditions (en is ethylenediamine, o-HB is o-hydroxybenzoate, and o-AB is o-aminobenzoate). Although the compounds were assumed to have similar structures and the Cu-Lig bond lengths and the cis and trans angles are acceptable for an octahedral structure, the geometric parameters of o-HB suggest that the copper atom has a plane square environment.     

Compounds of the menthane series. Synthesis of unsaturated primary alcohols with the <Emphasis Type="Italic">o</Emphasis>- and <Emphasis Type="Italic">p</Emphasis>-menthane skeletons

Precursors to terpene alcohols of the o- and p-menthane series (o-cimen-7-ol and o- and p-cimen-9-ols) were synthesized, and their reduction with lithium in ethylenediamine was studied. The reduction of o- and p-cimen-9-ols in the presence of isopropyl alcohol selectively afforded the corresponding 1,4-dihydro derivatives. Under analogous conditions, o-cimen-7-ol was converted into a mixture of unsaturated hydrocarbons. The reduction with lithium in ethylenediamine in the absence of isopropyl alcohol in all cases gave mixtures of menthene alcohols.     

The thermodynamic properties of the [(Me<Subscript>3</Subscript>Si)<Subscript>7</Subscript>C<Subscript>60</Subscript>]<Subscript>2</Subscript> fullerene complex

The temperature dependence of the heat capacity C _p ^o of the [(Me₃Si)₇C₆₀]₂ fullerene complex was measured for the first time using precision adiabatic vacuum calorimetry over the temperature range 6.7–340 K and high-accuracy differential scanning calorimetry at 320–635 K. For the most part, the error in the C _p ^o values was about ±0.5%. An irreversible endothermic effect caused by the splitting of the dimeric bond between fullerene fragments and the thermal decomposition of the complex was observed at 448–570 K. The thermodynamic characteristics of this transformation were calculated and analyzed. Multifractal analysis of the low-temperature (T < 50 K) heat capacity was performed, and conclusions were drawn concerning the character of the heterodynamicity of the structure. The experimental data obtained were used to calculate the standard thermodynamic functions C _p ^o (T), H ^o (T) ? H ^o (0), S ^o (T) ? S ^o (0), and G ^o (T) ? H ^o (0) over the temperature range from T → 0 to 445 K and estimate the standard entropy of formation of the compound from simple substances at 298.15 K. The standard thermodynamic properties of [(Me₃Si)₇C₆₀]₂ are compared with those of the (C₆₀)₂ dimer, the [(η⁶-Ph₂)₂Cr]⁺[C₆₀]^?? fulleride, and the initial C₆₀ fullerene.     

Structure and Reactivity of Bicyclo[2.2.1]hept-2-ene-<Emphasis Type="Italic">endo</Emphasis>-5,<Emphasis Type="Italic">endo</Emphasis>-6-dicarboxylic (endic) Acid Hydrazide

Establishing of the structure of hydrazinolysis product obtained from bicyclo[2.2.1]hept-2-ene-endo-5, endo-6-dicarboxylic (endic) acid was performed by preparation of the compound under alternative conditions followed by comparison of the characteristics and spectral parameters of the resulting substances, and also by quantum-chemical calculations by the density functional method of the chemical shifts in ¹H and ¹³C NMR spectra of different reaction products. The X-ray diffraction analysis of the hydrazide was also carried out. The compound obtained was assigned a structure of N-aminobicyclo[2.2.1] hept-2-ene-endo-5,endo-6-dicarboximide. The products were prepared by its reactions with arylsulfonyl chlorides, benzoyl chlorides, m-tolyl and p-toluene-sulfonyl isocyanates, phenyl isothiocyanate, with o-nitrobenzaldehyde, and oxiranes (1,2-epoxycyclohexane and 2,3-epoxypropylcarbazole). The aromatic sulfonamides, carboxamides, and ureas were epoxidized by performic acid obtained in situ from the formic acid and hydrogen peroxide. Products of [3+2]-cycloaddition of aryl azides to the strained double bond in the N-aminobicyclo[2.2.1] hept-2-ene-endo-5,endo-6-dicarboximide and its derivatives. The structures of compounds obtained were confirmed by their IR, 1H and 13C NMR spectra.     

DMT [(−)-(2<Emphasis Type="Italic">R</Emphasis>,3<Emphasis Type="Italic">R</Emphasis>)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol], a highly efficient host compound for nitroaromatic guests: selectivity,X-ray and thermal analyses

In this work, we reveal that the compound (?)-(2R,3R)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol (DMT) is a highly efficient host material for nitroaromatics o-nitrotoluene (o-NT), m-nitrotoluene (m-NT), p-nitrotoluene (p-NT) and nitrobenzene (NB). Each of these guests was included with a 2:1 host:guest ratio. The host displayed selectivity for p-NT and NB when these guests were mixed in equimolar proportions with any one of the other guest solvents, and the host recrystallized from this binary mixture. A selectivity order for the host in these conditions was thus noted to be NB?≈?p-NT?>?o-NT?>?m-NT. Furthermore, guests were also mixed in non-equimolar proportions and the host behaviour analysed, the results of which were in accordance with observations from the equimolar studies. Additionally, an equimolar quaternary experiment of all four guests provided a somewhat adjusted host selectivity order [p-NT (39.9%)?>?NB (30.2%)?>?m-NT (17.1%)?>?o-NT (12.8%)]. Single crystal diffraction analyses of all four complexes showed the crystals to share the same host packing, and comparable host–guest interactions were observed in each. However, thermal analyses, both DSC and TG, showed that the preferred guests p-NT and NB formed complexes with increased relative thermal stabilities, and this observation correlated with the selective behaviour of the host in competition experiments.     

Gas-phase synthesis of terbium and lutetium carboxylates

Gas-phase ligand exchange between volatile lanthanide dipivaloylmethanates (Ln(dpm)₃; Hdpm is dipivaloylmethane, Ln = Tb, Lu) and o-substituted aromatic carboxylic acids (HCarb = Hsal is o-hydroxybenzoic acid, Habz is o-aminobenzoic acid, Hpobz is o-phenoxybenzoic acid, Hpa is o-anilinobenzoic acid). The gas-phase reaction involves the formation of the mixed-ligand complex Ln (dpm)_3?n (Carb)n, which is subsequently converted into tris-carboxylate (Ln(Carb)₃) on heating of the product in vacuum.     

3,5-Di-<Emphasis Type="Italic">tert</Emphasis>-butyl-1,2-benzoquinone in the synthesis of quinolino[4,5-<Emphasis Type="Italic">bc</Emphasis>][1,5]benzoxazepines,aminophenols, and phenoxazines

Reaction of 3,5-di-tert-butyl-1,2-benzoquinone with 5-amino-4-chloroquinolines gave derivatives of a new fused heterocyclic system, substituted quinolino[4,5-bc][1,5]benzoxazepines. The molecular structure of 9,11-di-tert-butyl-2,4,6-trimethyl-7H-quinolino[4,5-bc][1,5]benzoxazepine was determined by X-ray analysis. 3,5-Di-tert-butyl-1,2-benzoquinone reacted with o-nitro-, o-acyl-, and o-methoxycarbonylanilines and some amino-substituted nitrogen-containing heterocycles to form the corresponding sterically hindered N-aryl-(hetaryl)-o-aminophenols. Di-tert-butyl-substituted phenoxazines were obtained as a result of thermal cyclization of intermediately formed quinone imines.     

Crystalline inclusion complexes of diterpenoid isosteviol with aromatic compounds

Crystalline inclusion complexes of diterpenoid isosteviol (ent-16-ketobeyeran-19-oic acid) with individual benzene, o-, m-, p-xylenes, ethylbenzene, isopropylbenzene, o-and m-nitoranilins, benzaldehyde, styrene and naphthalene are obtained and characterized by single crystal X-ray diffraction. As determined by GC and ¹H NMR spectroscopy, isosteviol selectively includes toluene from the equimolar benzene-toluene mixture, o-xylene from a commercial mixture of xylenes, o-and m-nitroanilins from their mixture with p-nitroanilin, and also styrene from styrene-ethylbenzene and styrene-isopropylbenzene mixtures thus yielding crystalline inclusion complexes.     

Synthesis,structure, and antibacterial properties of ternary rare-earth complexes with <Emphasis Type="Italic">o</Emphasis>-methylbenzoic Acid and 1,10-phenanthroline

Ternary rare-earth complexes with o-methylbenzoic acid (o-MBA) and 1,10-phenanthroline (Phen) Ln₂(o-MBA)₆(Phen)₂ · nH₂O(n = 0, 1) (Ln = La, Pr, Y, Yb) were synthesized and characterized by elemental analysis, IR, X-ray diffraction, and TG-DTG means. The complex La₂(o-MBA)₆(Phen)₂ · H₂O (I) is composed of two species of binuclear molecules in which the La³⁺ ion is coordinated with two nitrogen atoms of Phen and seven oxygen atoms of carboxylate groups. The carboxylate groups were bonded to La³⁺ in three modes: chelating-bidentate, bridging-bidentate, and chelating-bridging tridentate. The La³⁺ ion adopted a vigorous distorted monocapped square antiprism geometry. Complex I belongs to the triclinic crystal system, P space group, lattice parameters: a = 13.058(3), b = 12.7584(11), c = 20.773(4) Å, α = 101.18(3)°, β = 93.88(3)°, γ = 115.82(3)°, V = 3283.0(11)ų, Z = 2, ρ_calcd = 1.484 mg/m³, M _r = 1467.06, F(000) = 1476, μ = 1.350 mm^-1. The structure was refined to R _l = 0.0631 and wR ₂ = 0.1504. The antibacterial activity test indicates that these complexes exhibit better antibacterial ability against Escherichia coli and Staphylococcus aureus than the corresponding rare-earth chloride or o-MBA.     

Electrochemical transformations and anti/prooxidant activity of sterically hindered <Emphasis Type="Italic">o</Emphasis>-benzoquinones

The electrochemical properties of a series of sterically hindered o-benzoquinones in aprotic solvents were examined. The reaction of O₂ and KO₂ with o-benzoquinones and electrogenerated o-semiquinone radical anions was studied. The formation of o-semiquinone radical anions in the reactions of KO₂ with the studied o-quinones was detected using UV-visible and ESR spectroscopy. The influence of the test compounds on lipid peroxidation was considered at the molecular and tissue levels in vitro. In the most cases, o-quinones exhibit antioxidant activity, which varies depending on the type of lipid substrate.     

Synthesis of 6,8-substituted 4-(hydroxyphenylamino)- and 4-(aminophenylamino)-2-methylquinolines

A procedure has been developed for the synthesis of 4-(hydroxyphenylamino)- and 4-(aminophenylamino)-2-methylquinolines having a substituent in the 6(8)-position of the quinoline ring from the corresponding 4-chloro-2-methylquinolines and o-, m-, and p-aminophenols and o-, m-, and p-phenylenediamines.     

<Emphasis Type="Italic">N</Emphasis>-aryl-<Emphasis Type="Italic">o</Emphasis>-iminobenzoquinones as novel regulators of radical polymerization

The effect of a number of quinoid compounds on methyl methacrylate polymerization initiated by azo-bis(isobutyronitrile) has been studied. It has been revealed that N-aryl-o-iminobenzoquinones, in contrast to o-benzoquinones, can provide radical polymerization of methyl methacrylate in controllable mode. The efficiency of the compounds as chain growth regulators has been found to depend on their composition and reaction conditions. It has been established that 4,6-di-tert-butyl-N-(2,6-diethylphenyl)-o-iminobenzoquinone and 4,6-di-tert-butyl-N-(2,6-diisopropylphenyl)-o-iminobenzoquinone under radical initiation conditions provide the synthesis of poly(methyl methacrylate) with wide-range molecular weight, retaining polydispersity indices about ~1.4–1.8 up to deep conversions.     

Epoxidation and Heterocyclization of Arenesulfonamides of the Norbornene Series

Reactions of previously known and newly synthesized N-(bicyclo[2.2.1]hept-5-en-endo-2-ylmethyl)arenesulfonamides with monoperoxyphthalic acid generated in situ from phthalic anhydride and 30% hydrogen peroxide lead mostly to the corresponding N-arylsulfonyl-exo-2-hydroxy-4-azatricyclo[4.2.1.0^3,7]nonanes (azabrendanes). In some cases, N-(exo-5,6-epoxybicyclo[2.2.1]hept-5-en-exo-2-ylmethyl)arenesulfonamides were isolated as the only products or mixtures of alternative oxidation products were obtained. The presence of electron-acceptor nitro groups in the benzene ring and bulky substituents, primarily in the ortho position, is considered to be a structural factor preventing the primary oxidation products (epoxy derivatives) from undergoing heterocyclization.     

Synthesis and crystal structure of (<Emphasis Type="Italic">o</Emphasis>-Diaminobenzene)<Subscript>2</Subscript> Zn(OAc)<Subscript>2</Subscript>

The treatment of o-diaminobenzene with Zn ( OAc )₂ · 2H₂O in alcohol results in the formation of mononuclear bis(o-diaminobenzene)diacetate Zinc, Zn[C₈H₁₁N₂O₂]₂. Its structure was determined by X-ray diffraction analysis. The complex is also characterized by elemental analysis, ¹H NMR and IR. The crystal is monoclinic space group C2, parameters: a = 16.297(5), b = 4.775(3), c = 11.664(5) Å, β = 97.646(5)°, λ = 1.54184 Å, V = 899.6(7) ų, Z = 2, ρ _c = 1.476 g/cm³, M _r = 399.75, F(000) = 416.0, R ₁ = 0.0594, wR ₂ = 0.1439 for 995 observed reflections with I > 2σ(I).