Bromoperoxidases and functional enzyme mimics as catalysts for oxidative bromination—A sustainable synthetic approach

The discovery of enzymes that utilize hydrogen peroxide to oxidize bromide under physiological conditions provided a strong stimulus to the field of oxidative bromination. A synthetically useful enzyme, to catalyze the oxidation of bromide, for bromofunctionalization of donor-substituted arenes in solutions of hydrogen peroxide and sodium bromide, is a vanadate(V)-dependent bromoperoxidase from the brown alga Ascophyllum nodosum. This enzyme operates in homogeneous solutions of buffered aqueous tert-butanol (pH 6.2), or, to simplify repetitive use, in a two-phase system after immobilization onto magnetic beads. Synthesis of cyclic bromohydrin ethers (tetrahydrofurans and tetrahydropyrans) and vicinal dibromides from unsaturated hydrocarbons, on the other hand, occurs more effectively in polar aprotic solvents. Under such conditions the more lipophilic tert-butyl hydroperoxide serves as oxidant, which is activated by oxovanadium(V) complexes (functional bromoperoxidase mimics). Protons and bromide ions, which are consumed for in situ generation of bromine, are supplied in organic solution by fragmentation of 3-bromopropionic acids. The structure-reactivity data obtained from oxidations catalyzed by bromoperoxidases and functional enzyme mimics pose a valuable guideline for predicting selectivity in biomimetic synthesis of organobromines from terpenes, acetogenins, and pyrrole alkaloids.     

Kinetik der Bromierung von Phenolen und phenolischen Mekrkernverbindungen

The bromination of 15 dinuclear phenolic compounds (dihydroxydiphenylmethanes, methylene bisphenols) by molecular bromine in acetic acid was studied kinetically at 22°C. In all compounds the electrophilic substitution occurred inortho-position to the phenolic hydroxy group of the methyl phenol unit while the non reacting neighboring unit was differently substituted by H, CH₃,t-Bu and NO₂. A decrease in the reaction rate was observed in 2,2′-dihydroxydiphenylmethanes, where the +M-effect of the hydroxy group is diminished by an intramolecular hydrogen bond. The strength of this hydrogen bond may be influenced mainly by steric factors. Strong electron withdrawing substituents like NO₂ show a rate decreasing influence on the reactivity of the neighboring unit also in 2,4′- and 4,4′-dihydroxydiphenylmethanes.     

A novel pycnometer for density measurements of liquids at elevated temperatures

A novel pycnometer has been designed for density measurements at elevated temperatures (up to T=473.15 K). The pycnometer consists of a stainless steel cell connected to a small-bore tube. The main feature of the design includes a bored-through expansion fitting, which allows the overflow due to thermal expansion from the cell (via the small-bore tube) to collect in a pressurized line. Densities were measured for pure 1-butanol, pure n-heptane, and for mixtures {x_bCH₃(CH₂)₃OH + (1−x_b)CH₃(CH₂)₅CH₃}, from T=316.85 K to T=458.15 K, at a pressure of 4.93 MPa. Excess volumes were calculated and reported for these mixtures.     

Novel generation ponytails in fluorous chemistry: Syntheses of primary, secondary, and tertiary (nonafluoro-tert-butyloxy)ethyl amines

(Nonafluoro-tert-butyloxy)ethyl tosylate 4 was prepared in 65% yield from nonafluoro-tert-butanol 1 using commercially available reagents. Further reaction of 4 with HNR¹R² (R¹ = R² = H, CH₃; R¹ = H, R² = CH₃, (CH₂)₃C₈F₁₇, CH₂CH₂OC(CF₃)₃) affords the appropriate (CF₃)₃COCH₂CH₂NR¹R² amines in 20-69% yields. Improved overall yields of [(CF₃)₃COCH₂CH₂]_3−nNR_n to 1 were obtained by the reaction of (CF₃)₃CONa 2 and (XCH₂CH₂)_3−nNR_n (X = Cl, n = 0, 1, 2, R = CH₃; X = CH₃SO₂O, n = 1, R = CH₃SO₂) nitrogen mustards and a similar reactive β-substituted ethyl amine. The title amines are mobile colorless liquids and volatile with steam. The bulky fluorous ponytail (CF₃)₃CO(CH₂)₂ displays high acidic stability and increases fluorous character almost as much as the classical straight-chain C₈F₁₇(CH₂)₃ ponytail.     

Complexes of technetium(I) (Tc, Tc) pentacarbonyl core with π-acceptor ligands (tert-butyl isocyanide and triphenylphosphine): Crystal structures of [Tc(CO)5(PPh3)]OTf and [Tc(CO)5(CNC(CH3)3)]ClO4

A procedure was developed for preparing [^99mTcX(CO)₅] (X = Cl, Br, I) in a reasonable yield by high-pressure carbonylation with CO of ^99mTcO₄⁻ in aqueous solutions. In the synthesis, the substantial part of the target product is accumulated in the gas phase and can be transferred from the autoclave into various solvents when relieving the pressure. Compounds [^99mTcX(CO)₅] (X = Cl⁻, Br⁻, I⁻) are stable in solutions for several hours, but in the course of longer storage they gradually decompose to give the tricarbonyl species. Substitution of the halide ligands in [⁹⁹TcX(CO)₅] and [^99mTcX(CO)₅] with tert-butyl isocyanide and triphenylphosphine was studied. The structures of the complexes [Tc(CO)₅(PPh₃)]OTf and [Tc(CO)₅(CNC(CH₃)₃)]ClO₄ are presented.     

Experimental and theoretical study of N-(2-hydroxyethyl)morpholine betaine

N-(2-hydroxyethyl)morpholine betaine (HEMB) has been characterized by a single crystal X-ray analysis, FTIR spectroscopy and DFT calculations. The crystals are monoclinic, space group P2₁/c with a=10.273(2), b=9.360(2), c=9.447(2) Å and β=104.72(3)Å. Two molecules of HEMB form a centrosymmetric dimer (X2) connected by a pair of hydrogen bonds between the CH₂CH₂OH and COO⁻ groups, with the O?O distance of 2.672(2) Å. The morpholine ring adopts a chair conformation with the CH₂CH₂OH group in the axial and the CH₂COO⁻ group in the equatorial position. The structures of the dimer, B2, and two monomers, B1a and B1b, have been optimized by the B3LYP approach using the 6-31G(d,p) basis set. The computed structure of B2, agrees well with the experimental X2. From two stable monomeric conformers the more favored is B1a, with the intramolecular hydrogen bond with the O-H?O distance of 2.566 Å. The effects of hydrogen bonding and electrostatic interactions on the conformation of the molecules investigated have been discussed. The FTIR spectrum shows a broad absorption in the 3300-2600 cm⁻¹ region, typical of moderate O-H?O hydrogen bonds.     

Preparation of p-nitrocalix[n]arene methyl ethers via ipso-nitration and crystal structure of tetramethoxytetra-p-nitrocalix[4]arene

Nitration of p-tert-butylcalix[n]arene methyl ethers under a variety of reaction conditions has been examined. It has been determined that amongst different nitration procedures adopted (AlCl₃/KNO₃, HNO₃/CH₃COOH, HNO₃/(CH₃CO)₂O, cerium(IV) ammonium nitrate/CH₃COOH), ipso-nitration with CH₃COOH/HNO₃ gives best yields of p-nitrocalixarenes and work up conditions. ipso-Nitration of tetramethoxytetra-p-tert-butylcalix[4]arene gives tetramethoxytetra-p-nitrocalix[4]arene as triclinic crystals with space group with a=9.102(3) Å, b=11.623(3) Å, c=18.368(3) Å and α=77.99(2)°, β=81.10(2)°, γ=73.37(2)°. Its conformation is partial cone and it forms an exocylic 1:1 complex with DMF.     

The investigation of the (p,ρ,T) and (ps,ρs,Ts) properties of {(1−x)CH3OH + xLiBr} for the application in absorption refrigeration machines and heat pumps

The (p,ρ,T) and (p_s,ρ_s,T_s) properties of {(1−x)CH₃OH + xLiBr} over a wide range of state parameters are reported for the first time. The experiments were carried out in a constant volume piezometer over a temperature range from 298.15 K to 398.15 K, at 0.08421, 0.13617, 0.19692, 0.23133 and 0.26891 mole fractions and from atmospheric pressure up to 60 MPa. The experimental uncertainties are ΔT=±3 mK for temperature, Δp=±5·10⁻² MPa for high pressure and Δp=±5·10⁻⁴ MPa for atmospheric pressure, Δρ=±3·10⁻² kg · m⁻³ for density. An equation of state was derived for correlation of the experimental data of the solutions.     

Gas transport in polybutadiene treated with aqueous bromine

Diffusion, solubility, and permebility coefficients were measured for He, Co₂, Ar, and CH₄ in polybutadiene (PB) and in polybutadiene reacted in the solid state to various extents with aqueous bromine. Analysis of the sorption curves and X-ray emission spectra showed that the bromination created a heterogeneous membrane with an outer brominated skin and an unreacted core. At relatively low extent of bromination, the diffusion and permeability coefficients for CO₂, Ar, and CH₄ decreased by two orders of magnitude, while the transport coefficients for He were virtually unchanged. The permeability coefficients for CO₂, Ar, and CH₄ became immeasurably small after about 3% bromination. The ideal separation factor for gas pairs with different molecular size increased with bromination, suggesting applications in gas separation processes. © 1993 John Wiley & Sons, Inc.     

Halogenation of ketones with N-halosuccinimides under solvent-free reaction conditions

Several aryl substituted ketones, cyclic ketones, 1,3-diketones and a β-ketoamide were halogenated with N-halosuccinimides under solvent-free reaction conditions (SFRC) at various temperatures (20-80 °C), whereas less enolized ketones required the presence of an acid catalyst (p-toluenesulfonic acid, PTSA). Bromination of substituted acetophenones obeys first order kinetics v=k_Br[ketone] and the following correlation with the keto-enol equilibrium constant: log k_Br=0.3pK_E+C₁, less enolized substrates being more reactive; the moderate positive charge developed in the rate determining step was confirmed by the Hammett correlation (ρ=−0.5). On the other hand, in cyclic ketones an opposite relation was observed: log k_Br=−0.6pK_E+C₂, indicating higher reactivity of substrates with higher enolization constant (K_E). The important role of the nature of the solvent (MeCN, MeOH) in preorganization of the ketone-NBS-PTSA mixture prior to SFRC bromination was found.     

Expedient synthesis of 4-O-methylhonokiol via Suzuki-Miyaura cross-coupling

Concise and practical synthesis of 4-O-methylhonokiol was achieved in 34% overall yield. The key features of our synthesis include chemoselective ortho-mono bromination of phenol as well as biaryl formation via Suzuki-Miyaura cross-coupling, in which bromophenol was reacted with potassium aryltrifluoroborate using Pd(OAc)₂ and RuPhos under microwave conditions.     

Oxidation of substituted pyridines by dimethyldioxirane: kinetics and solvent effects

The oxidation of a series of substituted pyridines by dimethyldioxirane (1) produced the expected N-oxides in quantitative yields. The second order rate constants (k₂) for the oxidation of a series of substituted pyridines (2a-g) by dimethyldioxirane were determined in dried acetone at 23 °C. An excellent correlation with Hammett sigma values was found (ρ = −2.91, r = 0.995). Kinetic studies for the oxidation of 4-trifluoromethylpyridine by 1 were carried out in the following dried solvent systems: acetone (k₂ = 0.017 M⁻¹ s⁻¹), carbon tetrachloride/acetone (7:3; k₂ = 0.014 M⁻¹ s⁻¹), acetonitrile/acetone (7:3; k₂ = 0.047 M⁻¹ s⁻¹), and methanol/acetone (7:3; k₂ = 0.68 M⁻¹ s⁻¹). Kinetic studies of the oxidation of pyridine by 1 versus mole fraction of water in acetone [k₂ = 0.78 M⁻¹ s⁻¹ (χ = 0) to k₂ = 11.1 M⁻¹ s⁻¹ (χ = 0.52)] were carried out. The results showed the reaction to be very sensitive to protic, polar solvents.     

Critical parameters for isobutane determined by the image analysis

(p, ρ, T) Measurements and visual observations of the meniscus for isobutane were carried out carefully in the critical region over the range of temperatures: −15 mK ? (T − T_c) ? 35 mK, and of densities: −7.5 kg · m⁻³ ? (ρ − ρ_c) ? 7.5 kg · m⁻³ by a metal-bellows volumometer with an optical cell. Vapor pressures were also measured at T = (310, 405, 406, 407, and 407.5) K. The critical point of T_c and ρ_c was determined by the image analysis of the critical opalescence which is proposed in this study. The critical pressure p_c was determined to be the pressure measurement at the critical point. Comparisons of the critical parameters with values given in the literature are presented.     

Soluble {[Rh2(μ-OOCCH3)2(dbbpy)2][BF4]}n molecular wire and [Rh2(μ-OOCCH3)2(dbbpy)2L2] complexes; dbbpy = 4,4′-di-tert-butyl-2,2′-bipyridine: Synthesis and physicochemical characterization

Binuclear Rh(II) compounds [Rh₂(μ-OOCCH₃)₂(dbbpy)₂(H₂O)₂](CH₃COO)₂ (1) (dbbpy = 4,4′-di-tert-butyl-2,2′-bipyridine), [Rh₂(μ-OOCCH₃)₂(dbbpy)₂(H₂O)₂](BF₄)₂·H₂O·CH₃CN (2), [Rh₂(CH₃COO)₂(C₁₈H₂₄N₂)₂(CH₃CN)₂](BF₄)₂·4CH₃CN (3) and {[Rh₂(μ-OOCCH₃)₂(dbbpy)₂][BF₄]}_n (4) have been synthesized and characterized with spectroscopic methods. Structure of complex 3 has been determined using X-ray crystallography. Rhodium atoms in compound 3 have distorted octahedral coordination with O and N atoms in equatorial positions and Rh atom and CH₃CN molecule in axial coordination sites. Reduction of rhodium(II) compounds with aqueous 2-propanol leads to the formation of polymetallic compound {[Rh₂(μ-OOCCH₃)₂(dbbpy)₂][BF₄]}_n (4) containing [Rh₂]³⁺ core. Compound 4 shows strong antiferromagnetic properties, μ = 0.18–1.73 M.B. in the range 1.8–300 K, J = −597 cm⁻¹. Electrochemistry of compounds 3 and 4 in CH₃CN has been investigated. Compound 4 exhibits a poorly reversible oxidation system at E_1/2 = −0.92 V (ΔE_p = 0.19 V) and in solution in DMF is slowly oxidized to 3 even in total absence of oxygen. Complex 3 is irreversibly oxidized to Rh(III) compound at E_pa = 1.48 V and irreversibly reduced at E_pc = −1.02 V to lead to the unstable polynuclear complex 4 in CH₃CN.     

Preparation and properties of new ortho-linked polyamide-imides bearing ether, sulfur, and trifluoromethyl linkages

A CF₃-containing diamine, 2,2′-thiobis-[4-methyl(2-trifluoromethyl)4-aminophenoxy) phenyl ether] (DA), was successfully synthesized from 2-2′-sulfide-bis-(4-methyl phenol) and 2-chloro-5-nitrobenzotrifluoride. The sulfur containing diimide-diacid (DIDA) was prepared by condensation reaction of diamine DA and trimellitic anhydride. A series of novel organic-soluble polyamide-imides (PAIs) bearing flexible ether and sulfide links, electron-withdrawing trifluoromethyl groups and ortho-phenylene units were synthesized from DIDA, by direct polycondensation with various aromatic diamines in N-methyl-2-pyrrolidone using triphenyl phosphite and pyridine as a condensing agent in the presence of dehydrating agent (LiCl). The polyamide-imides were obtained in high yields and possessed inherent viscosities in the range of 0.42-0.95 dL g⁻¹. All of the polymers were amorphous in nature, showed outstanding solubility and could be easily dissolved in amide-type polar aprotic solvents (e.g., N-methyl-2-pyrrolidone, N,N-dimethylacetamide, and N,N-dimethylformamide) and even dissolved in less polar solvents (e.g., pyridine and tetrahydrofuran). They showed good thermal stability with glass transition temperatures between 195-245 °C, 10% weight loss temperatures in excess of 485 °C, and char yields more than 50% at 700 °C in nitrogen atmosphere. Moreover, these PAIs possessed low refractive indexes (n = 1.57-1.59) and low birefringence (Δ ≈ 0.02) due to the trifluoromethyl pendent groups and thioether bridged ortho-catenated aromatic rings that interrupt chain packing and increase free volume.     

Zwitterionic hydrophilic interaction chromatography coupled with post-column derivatization for the analysis of glutathione in wine samples

In this study the development, validation and application of a new chromatographic method for the determination of glutathione (GSH) in wine samples is presented. The separation of the GSH was carried out using a sulfobetaine-based hydrophilic interaction chromatography (HILIC) analytical column whereas its detection was carried out spectrofluorimetrically (λ_ext/λ_em = 340/455 nm) after post-column derivatization with o-phthalaldehyde. GSH was separated efficiently from matrix endogenous compounds of wines by using a mobile phase of 15 mmol L⁻¹ CH₃COONH₄ (pH = 2.5)/CH₃CN, 35/65% (v/v). The parameters of the post-column reaction (pH, amount concentration of the reagent and buffer solution, flow rate, length of the reaction coil) were investigated. The linear determination range for GSH was 0.25–5.0 μmol L⁻¹ and the LOD was 19 nmol L⁻¹. No matrix effect was observed, while the accuracy was evaluated with recovery experiments and was ranged between 89% and 108%.     

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.     

Free radical bromination by the H2O2-HBr system on water

An aqueous solution of hydrogen peroxide and hydrogen bromide illuminated by a 40 W incandescent light bulb serves as a source of bromine radicals. Various substituted toluenes (H, Me, tBu, Br, COOEt, COPh, NO₂) were brominated at the benzyl position. This haloperoxidase-like system for benzylic bromination does not require the presence of metal ions or an organic solvent for efficient conversion of methyl-arenes to benzyl bromides.     

Synthesis and structure of a 1,6-hexyldiamine heptaborate, [H3N(CH2)6NH3][B7O10(OH)3]

A new 1,6-hexyldiamine heptaborate, [H₃N(CH₂)₆NH₃][B₇O₁₀(OH)₃] (1), has been solvothermally synthesized and characterized by single-crystal X-ray diffraction, FTIR, elemental analysis, and thermogravimetric analysis. Compound 1 crystallizes in monoclinic system, space group P2₁/n with a=8.042(2) Å, b=20.004(4) Å, c=10.103(2) Å, and β=90.42(3)°. The anionic [B₇O₁₀(OH)₃]_n²ⁿ⁻ layers are interlinked via hydrogen bonding to form a 3D supramolecular network containing large channels, in which the templated [H₃N(CH₂)₆NH₃]²⁺ cations are located.     

Mechanism of isomerization of ortho or para bromo phenols in superacids

In superacids ortho or para bromo phenols are isomerized into the meta bromo isomers. In SbF₅-HF, the process is intramolecular and proceeds by a 1,2-Br shift. In CF₃SO₃H, the mechanism involves loss of bromine, followed by meta bromination.