Brominating Agent Research Articles

Bromination of phenol red mediated by vanadium(V) peroxo complexes at pH 6.5

The kinetics of bromination of phenol red (HPhR) to yield bromophenol blue (BrPhB) was studied at pH 6.5, in the presence of peroxovanadium(V) species generated by acid decomposition of [VO(O2)2(NH3)]− and of [O{VO(O2)2}2]4−. In the concentration ranges 10−6–10−7 (HPhR), (1.5–8.0) × 10−4 (vanadium complexes) and 0.004–0.12 mol dm−3 (bromide), the rate law is R = k[V]T [Br−][HS], where HS is the substrate undergoing bromination in the rate determining step, with k = 2.49 × 105 dm6 mol−2 s−1. Acid treatment of the precursor complexes yields a mixture of [VO(O2)L]n complexes, with L = H2O, [VO(O2)(H2O)]+, or O22−, [VO(O2)2]−. Alkalinization leads to active species that react with bromide to yield a brominated vanadium complex (e.g. [VO(O2)Br]), which is postulated to be the active bromination agent. Kinetic data rule out the mediation of hypobromous acid. The results support the idea that five-co-ordinated vanadium species are required in the bromination reaction.

A New Synthesis and Application of N, N'-Dibromo-N, N' -1,2-Ethylene bis(2,5-Dimethyl Benzene Sulfonamide); As a Novel Selective Bromination Agent for Aromatic Compounds

Reaction Between Novel Compound; N, N′ dibromo-N, N′ -1,2- ethylene bis(2,5- dimethyl benzene sulfonamide) and aromatic compounds in the carbontetrachloride produces bromo aromatic compounds. In the case of benzene rings that contain mono activated substituted, only para - bromo isomer was formed. At the presence of benzoyl peroxide in the reaction mixture α - Hydrogen from alkyl side chain was substituted with bromine.

Benzimidazolium Bromochromate-A New Reagent for Bromination and Oxidation

The new reagent, benzimidazolium bromochromate (BIBC), apart from being efficient as an oxidant for alcohols, also functions as a good brominating agent for aromatic compounds.

3-Bromotyrosine and 3,5-dibromotyrosine are major products of protein oxidation by eosinophil peroxidase: potential markers for eosinophil-dependent tissue injury in vivo.

Detection of specific reaction products is a powerful approach for dissecting out pathways that mediate oxidative damage in vivo. Eosinophil peroxidase (EPO), an abundant protein secreted from activated eosinophils, has been implicated in promoting oxidative tissue injury in conditions such as asthma, allergic inflammatory disorders, cancer, and helminthic infections. This unique heme protein amplifies the oxidizing potential of H2O2 by utilizing plasma levels of Br- as a cosubstrate to form potent brominating agents. Brominated products might thus serve as powerful tools for identifying sites of eosinophil-mediated tissue injury in vivo; however, structural identification and characterization of specific brominated products formed during EPO-catalyzed oxidation have not yet been reported. Here we explore the role of EPO and myeloperoxidase (MPO), a related leukocyte protein, in promoting protein oxidative damage through bromination and demonstrate that protein tyrosine residues serve as endogenous traps of reactive brominating species forming stable ring-brominated adducts. Exposure of the amino acid L-tyrosine to EPO, H2O2, and physiological concentrations of halides (100 mM Cl-, </=100 microM Br-) produced two new major products with distinct retention times on reverse phase HPLC. The products were identified as 3-bromotyrosine and 3, 5-dibromotyrosine by electrospray ionization mass spectrometry and multinuclear (1H and 15N) NMR spectroscopy. Formation of the ring-brominated forms of the amino acid occurred readily at neutral pH with the enzymatic system and a variety of reactive brominating species, including HOBr/OBr-, N-bromoamines, and N,N-dibromoamines. Addition of primary amines (e.g., Nalpha-acetyllysine and taurine) to L-tyrosine exposed to either HOBr/OBr- or the EPO-H2O2-Br- system enhanced phenolic ring bromination, suggesting N-bromoamines are preferred brominating intermediates in these reactions. Reduction of N-bromoamines (e.g., Nalpha-acetyl,Nepsilon-bromolysine) by L-tyrosine was shown to result in the loss of reactive halogen with a near stoichiometric increase in the level of tyrosine ring bromination (i.e., carbon-bromine bonds). Although both EPO and MPO could use Br- to halogenate protein tyrosine residues in vitro, only EPO effectively brominated the aromatic amino acid at physiological levels of halides and H2O2. Collectively, these results suggest that 3-bromotyrosine and 3,5-dibromotyrosine are attractive candidates for serving as molecular markers for oxidative damage of proteins by reactive brominating species in vivo. They also suggest that in biological mixtures where amine groups are abundant, the trapping of EPO-generated HOBr/OBr- as N-bromoamines will serve to effectively "funnel" reactive brominating equivalents to stable ring-brominated forms of tyrosine.

Electron microscope characterization of AgBr heterojunctions with silver carboxylates and their influence on the morphology of developed silver particles in thermally developed photomaterials

Silver halide crystals formed during in situ treatment of silver stearate crystals with various halidizing agents are observed by scanning and transmission electron microscopy to form on the lateral edges of the silver carboxylate crystals. The location of the silver halide phase on the crystal edge is dictated by the anisotropic structure of the silver stearate crystal lattice, specifically, the layered structure in which silver ion layers are separated by long-chain hydrocarbon groups. The formation of AgBr on the lateral faces of these crystals is proposed to be typical not only of the formation of silver halide on silver stearate but also for all silver carboxylates of the general formula [AgCnH2n-1O2]2 when the crystals of these silver carboxylates have anisotropic, layered structures. The silver bromide/silver carboxylate heterojunction in an in situ system has been clearly observed by transmission electron microscopy. The heterojunction is comprised of a distorted silver carboxylate lattice, which accommodates the misalignment between the AgBr and [Ag(O2CR)]2 crystal lattices. The nature of heterojunction between the AgBr and the silver carboxylate when the AgBr is prepared separately from the preparation of the silver carboxylate differs from the in situ heterojunction. In this case, a layered compound, proposed to have a Ag1-xNaxSt composition, forms between the AgBr and the silver stearate which is a unique feature of this interface. The differences in the structure of interfaces formed between the silver halide and the silver fatty acid complex result in different silver particle morphologies during thermal development of exposed photothermographic films. The developed silver is generally filamentary when the photothermographic material contains silver halide prepared by the in situ exchange reaction between silver carboxylate and a brominating agent. If the photothermographic material is prepared from previously synthesized silver halide crystals, the preformed AgBr route, the developed silver generally crystallizes as dendritic crystals. Microsc. Res. Tech. 42:152–172, 1998. © 1998 Wiley-Liss, Inc.

Electron microscope characterization of AgBr heterojunctions with silver carboxylates and their influence on the morphology of developed silver particles in thermally developed photomaterials.

Silver halide crystals formed during in situ treatment of silver stearate crystals with various halidizing agents are observed by scanning and transmission electron microscopy to form on the lateral edges of the silver carboxylate crystals. The location of the silver halide phase on the crystal edge is dictated by the anisotropic structure of the silver stearate crystal lattice, specifically, the layered structure in which silver ion layers are separated by long-chain hydrocarbon groups. The formation of AgBr on the lateral faces of these crystals is proposed to be typical not only of the formation of silver halide on silver stearate but also for all silver carboxylates of the general formula [AgCnH2(n-1)O2]2 when the crystals of these silver carboxylates have anisotropic, layered structures. The silver bromide/silver carboxylate heterojunction in an in situ system has been clearly observed by transmission electron microscopy. The heterojunction is comprised of a distorted silver carboxylate lattice, which accommodates the misalignment between the AgBr and [Ag(O2CR)]2 crystal lattices. The nature of heterojunction between the AgBr and the silver carboxylate when the AgBr is prepared separately from the preparation of the silver carboxylate differs from the in situ heterojunction. In this case, a layered compound, proposed to have a Ag1-xNaxSt composition, forms between the AgBr and the silver stearate which is a unique feature of this interface. The differences in the structure of interfaces formed between the silver halide and the silver fatty acid complex result in different silver particle morphologies during thermal development of exposed photothermographic films. The developed silver is generally filamentary when the photothermographic material contains silver halide prepared by the in situ exchange reaction between silver carboxylate and a brominating agent. If the photothermographic material is prepared from previously synthesized silver halide crystals, the preformed AgBr route, the developed silver generally crystallizes as dendritic crystals.

Quinolinium Bromochromate-A New Reagent for Bromination and Oxidation

Abstract The new reagent, quinolinium bromochromate (QBC), apart from being efficient as an oxidant for alcohols, also functions as a good brominating agent for aromatic compounds.

Oxidation of Bromide by the Human Leukocyte Enzymes Myeloperoxidase and Eosinophil Peroxidase: FORMATION OF BROMAMINES

Myeloperoxidase and eosinophil peroxidase catalyzed the oxidation of bromide ion by hydrogen peroxide (H2O2) and produced a brominating agent that reacted with amine compounds to form bromamines, which are long-lived oxidants containing covalent nitrogen-bromine bonds. Results were consistent with oxidation of bromide to an equilibrium mixture of hypobromous acid (HOBr) and hypobromite ion (OBr-). Up to 1 mol of bromamine was produced per mole of H2O2, indicating that bromamine formation prevented the reduction of HOBr/OBr- by H2O2 and the loss of oxidizing and brominating activity. Bromamines differed from HOBr/OBr- in that bromamines reacted slowly with H2O2, were not reduced by dimethyl sulfoxide, and had absorption spectra similar to those of chloramines, but shifted 36 nm toward higher wavelengths. Mono- and di-bromo derivatives (RNHBr and RNHBr2) of the beta-amino acid taurine were relatively stable with half-lives of 70 and 16 h at pH 7, 37 degrees C. The mono-bromamine was obtained with a 200-fold excess of amine over the amount of HOBr/OBr- and the di-bromamine at a 2:1 ratio of HOBr/OBr- to the amine. In the presence of physiologic levels of both bromide (0.1 mM) and chloride (0.1 M), myeloperoxidase and eosinophil peroxidase produced mixtures of bromamines and chloramines containing 6 +/- 4% and 88 +/- 4% bromamine. In contrast, only the mono-chloramine derivative (RNHCl) was formed when a mixture of hypochlorous acid (HOCl) and hypochlorite ion (OCl-) was added to solutions containing bromide and excess amine. The rapid formation of the chloramine prevented the oxidation of bromide by HOCl/OCl-, and the chloramine did not react with bromide within 1 h at 37 degrees C. The results indicate that when enzyme-catalyzed bromide or chloride oxidation took place in the presence of an amine compound at 10 mM or higher, bromamines were not produced in secondary reactions such as the oxidation of bromide by HOCl/OCl- and the exchange of bromide with chlorine atoms of chloramines. Therefore, the amount of bromamine produced by myeloperoxidase or eosinophil peroxidase was equal to the amount of bromide oxidized by the enzyme. Bromide was preferred over chloride as the substrate for both enzymes.

Bromine trifluoride as a bromination agent for deactivated aromatic compounds

Bromine trifluoride in a mixture with elemental bromine can be used as a bromination agent for deactivated aromatic compounds.The method comprises reacting an equimolar mixture of elemental bromine and bromine trifluoride with the aromatic compound, practically at room temperature. In all cases demonstrated, the reaction is instantaneous and no catalyst is required.In most cases, when electron withdrawing group is attached to the aromatic ring, the bromination takes place at the expected meta position.The bromination method can be particularly applicable when extremely deactivated rings like dinitrobenzenes and nitroacetophenones have to be brominated.

Bromination of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(2?-difluoromethoxyphenyl)-1,4-dihydropyridine (foridone)

The action of mild brominating agents (pyridinium bromide-perbromide, dioxan dibromide N-bromosuccinimide, and N-bromoacetamide) on 2,6-dimethyl-3,5-dimethoxy-carbonyl-4-(2′-difluoromethoxyphenyl)-1,4-dihydropyridine (Foridone) has been studied. Depending on reaction conditions, furo-, difuro-, and dibromomethyl-1,4-dihydropyridines are obtained together with certain oxidized forms.

Eosinophils Preferentially Use Bromide to Generate Halogenating Agents

Human eosinophils preferentially utilize bromide to generate a brominating agent, even at physiological halide concentrations, where chloride (140 mM) is over 1000-fold greater than bromide (20-100 microM). Under the same conditions, neutrophils use chloride to generate a chlorinating agent. The total amount of active halogen trapped by 1,3,5-trimethoxybenzene from eosinophils increases by over 2-fold as the added bromide concentration increases from 0 to 100 microM, with approximately 40 nmol of halogen trapped per million cells at the highest bromide level. At least 25-35% of the oxygen consumed by stimulated eosinophils is directed toward the generation of halogenating species. Since the relative halogenating behavior of eosinophil peroxidase and neutrophil myeloperoxidase in this bromide range is essentially identical to that of the cells, the specificity of eosinophils toward bromide is intrinsic to eosinophil peroxidase and not to any special cellular properties. These results suggest that human eosinophils use bromide in vivo and that a deficiency of bromide may influence their ability to produce halogenating agents.

Reaction of sulfoxide hydrochlorides and hydrobromides with trisubstituted olefins

1. Dimethyl, diphenyl, and tetramethylene sulfoxide hydrochlorides react with methylheptenyl, citronellyl, and geranyl acetates to give predominantly the allylic chlorination products. 2. These findings are preferably to be regarded as involving AdE reactions between the weakly electrophlic hydroxy and (or) chlorosulfonium cation and the trisubstituted C=C bond in these olefins at the key stage. 3. The addition of lithium perchlorate has been found to accelerate this reaction. 4. Sulfoxide hydrobromides are highly selective brominating agents for the terminal grouping in isopropenoid oligoolefins.

Synthesis of pyridine and quinoline derivatives of poly(methyl methacrylate): their uses as brominating agents

Nucleophilic substitutions of 2-picolinyl and 2-quinaldinyl-lithium onto the carbonyls of the ester moieties of poly(methyl methacrylate) (PMMA) followed by reduction have been carried out for functionalization of PMMA. Complexation of the polymeric pyridine derivatives with bromine gave various types of polymeric brominating agents. The activities of these crosslinked reagents were investigated for direct brominations of of carbonyl compounds, alkenes and arenes. There are excellent yields of the brominated products; the polymeric by-product can be simply converted back to the reagent without loss of activity.

Selective bromination of the aromatic ring in ω-phenylpolyoxaalkanes and alkanols in micelles

The regioselectivity of bromination of ω -phenylpolyoxaalkanes and alkanols by bromine in aqueous solution of dodecyl sulfate (SDS) and aqueous solution of cetyltrimethylammonium bromide (CTAB) are shown to be related to the average orientation of substrate as indicated by 1H NMR studies. Thus ortho-bromination is promoted at higher concentrations of the surfactant relative to pure water. In contrast, at an equal ratio of the surfactant and substrate para-bromination is promoted. The results are discussed with respect to the average orientation of substrate in a micellar microenvironment and the formation of an ether-bromine comples as possible bromination agent.

ベンジルトリメチルアンモニウムトリブロミド

Benzyltrimethylammonium tribromide (BTMA Br3), a stable solid brominating agent, can be prepared by the reaction of benzyltrimethylammonium chloride with sodium bromate and hydrobromic acid in aqueous solution. In this article, the useful synthetic applications of BTMA Br3 are described. The reactions of aromatic compounds such as phenols, aromatic amines, aromatic ethers and acetanilides with BTMA Br3 in dichloromethane-methanol at room temperature give easily bromo-substituted products in good yields, respectively. On the reaction of arenes with BTMA Br3, electrophilic.bromination occurs in acetic acid in the presence of zinc chloride, and benzylic brominatlon proceeds in refluxing benzene in the presence of AIBN. Furthermore, BTMA Br3 reacts with acetyl derivatives to give dibromoacetyl derivatives, and with alkenes to give 1, 2-dibromo adducts.

Formation of furo- and difuro-1,4-dihydropyridines in the bromination 0f 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-nitrophenyl)-1,4-dihydropyridine

Furo- and difuro-1,4-dihydropyridines were obtained by bromination of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-nitrophenyl)-1,4-dihydropyridine with mild brominating agents (pyridinium bromide perbromide, N-bromosuccinimide, and dioxane dibromide).

Novel aromatic bromination using BrF prepared directly from the corresponding elements

BrF, made directly from the corresponding elements, may be used without any catalyst as an efficient electrophilic brominating agent in its reactions with activated and deactivated aromatic rings.

Titrimetric and Spectrophotometric Determination of Acetylenic Hypnotics, Using Brominating Agents

Titrimetric and spectrophotometric titration methods are described for the quantitative determination of acetylenic hypnotics ethchlorvynol, ethinamate, and meparfynol carbamate as pure substances and in dosage forms. The methods involve the use of different brominating agents. A known excess of the reagent is added and, after the specified time, the residual reagent is determined iodometrically. These procedures permit semimicro determination (1-20 mg) of the drug. Recoveries ranged from 98.48 +/- 0.76 to 102.74 +/- 2.60%. The procedures have been successfully applied to pharmaceutical dosage forms; the results agree well with those for compendial methods.

Determination of Some Quinoline Derivatives with Organic Brominating Agents

Abstract A titrimetric method has been developed in which the determination of some quinoline derivatives was possible. The proposed method involves the use of either, 1,3-Dibromo, 5,5-dimethylhydantoin (DBH) or N-Bromosuccinimide (NBS) as titrants. Primaquine is determined by direct titration and the end point is detected either visually using dye-stuffs as indicators or potentiometrically. Amodiaquine, chloroquine, quinine and quinidine are determined adopting the back-titration procedure. Also, an assay procedure was described for the analysis of mixture of primaquine and amodiaquine when dispensed together. The suggested methods could be applied to pharmaceutical preparation containing the studied compounds and the results obtained were compared favourably with those given with the official ones. The reaction pathways were suggested and confirmed through an analytical study of the reaction products.

Cross-linked poly-(4-vinylpyridine–styrene)–bromine complexes as stereoselective brominating agents

Cross-linked poly(styrene–4-vinylpyridine) beads, containing 40–43% of pyridine rings, were transformed with bromine to provide three types of brominating agents (1), (2), and (3). Reactions of cis- and trans-1-phenylpropene with (1), (2), and (3) resulted in a high degree of anti-stereoselectivity. The reactivity increases from (1) to (3); solvent polarity has no significant effect on stereoselectivity, but affects the reactivity, being significantly greater in acetonitrile and chloroform than in cyclohexane and dioxan. Bromination of 1-phenylcyclohexene with (1) and (3) resulted in the formation of trans-1,2-dibromo-1-phenylcyclohexane (9) and 3-bromo-2-phenylcyclohexene (10), the temperature affecting only the ratio of the products. Bromination of norbornene with the reagents (1), (2), and (3) resulted in the formation of seven products: 2-exo-bromonorbornane (12), 7-bromonortricyclane (13), 2-exo, 3-endo-dibromonorbornane (14), 2-exo-7-anti-dibromonorbornane (15), 2-exo, 5-endo-dibromonorbornane (16), 2-exo, 5-exo-dibromonorbornane (17), and 2-exo, 7-syn-dibromonorbornane (18).