Electrophilic Bromination Research Articles

Electrophilic Bromination of Alkenes: Environmental, Health and Safety Aspects of New Alternative Methods

More than twenty new alternative methods for bromination of alkenes have been evaluated taking into consideration their resource demands, waste production as well as environmental, health and safety aspects. The cost of bromine and the substances designated to circumvent the application of molecular bromine have also been taken into account. As bromine is only one of several problematic substances being used, its avoidance-by applying bromine supported on solid material or by performing the in situ generation of bromine-does not significantly reduce the technological requirements. On the contrary, the resource demands and amount of waste produced by most new methods are significantly higher compared to the standard methods, especially if the recycling of a carrying agent is not efficient. The method using hydrobromic acid and hydrogen peroxide can be regarded as a competitive alternative to the standard method. The application of certain carrying agents could be interesting, because solvents such as carbon tetrachloride or chloroform used during synthesis could be replaced with less problematic ones during work-up. However, problems associated with these alternatives are not resolved as yet.

A new method of bromination of aromatic rings by an iso-amyl nitrite/HBr system

Abstract A mixture of iso-amyl nitrite/HBr is shown to be a mild and efficient reagent for electrophilic aromatic bromination. The reaction succeeds with slightly activated arenes and heterocyclic compounds. By using HCl instead of HBr, chlorination can also be performed in few cases. The i-amONO2/HBr mixture can also be utilized for bromination in the α-position of electron withdrawing groups. A possible mechanism is briefly discussed.

A Stable Iridabenzene Formed from an Iridacyclopentadiene Where the Additional Ring-Carbon Atom Is Derived from a Thiocarbonyl Ligand

The cationic thiocarbonyl complex [Ir(CS)(MeCN)(PPh3)2][CF3SO3] (1) reacts sequentially with ethyne and LiCl to give the iridacyclopentadiene Ir[C4H4]Cl(CS)(PPh3)2 (2), which in turn when heated with methyl triflate followed by addition of LiCl produces the stable, purple, iridabenzene Ir[C5H4(SMe-1)]Cl2(PPh3)2 (3). This iridabenzene undergoes electrophilic aromatic bromination in the position para to the SMe substituent to form Ir[C5H3(SMe-1)(Br-4)]Br2(PPh3)2 (4).

Amidines as Potent Nucleophilic Organocatalysts for the Transfer of Electrophilic Bromine from N‐Bromosuccinimide to Alkenes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of 6-Substituted Pyrido[2,3-b]indoles by Electrophilic Substitution

Regioselective electrophilic aromatic substitutions, acylation, bromination, and formylation, of unprotected pyrido[2,3-b]indole (α-carbolines) at the C-6 position are described. Alter­native conditions for the nitration were investigated, which led to the ­unexpected appearance of the minor C-8 isomer.

Regioselective Aromatic Electrophilic Bromination with Dioxane Dibromide under Solvent‐Free Conditions.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Efficient Electrophilic Cobromination of Alkenes and Bromination of Activated Arenes with Bromodichloroisocyanuric Acid under Mild Conditions

Efficient methodologies for the preparation of bromo­dichloroisocyanuric acid were developed (70-75%). This new ­reagent is very efficient for regioselective electrophilic bromination of activated arenes (86-93%) and cobromination of alkenes with oxygenated nucleophiles (31-98%). The reaction of bromodi­chloroisocyanuric acid with anisole, acetanilide, N-methyl­acetanilide leads to 4-substituted monobromoarene and with 2-methoxynaphthalene leads to 1-bromo-2-methoxynaphthalene. Alkenes were cobrominated in the presence of oxygenated nucleophilic solvents (water, alcohols, and acetic acid), leading to the corresponding bromohydrins, β-bromoethers and β-bromoacetates.

Amidines as potent nucleophilic organocatalysts for the transfer of electrophilic bromine from N-bromosuccinimide to alkenes

(±)- iso-Amarine is a potent organocatalyst at 1 mol % loading for both the bromoacetoxylation of alkenes with added acetic acid and bromolactonisation of unsaturated carboxylic acids with stoichiometric NBS as the electrophilic bromine source. A simple bromoamidine with an N–Br bond has been characterised crystallographically for the first time. Asymmetric induction in the bromination reactions with enantiopure amidines was zero.

Regioselective 15-bromination and functionalization of a stable synthetic bacteriochlorin.

5-Methoxy-8,8,18,18-tetramethyl-2,12-di-p-tolylbacteriochlorin (MeO-BC) undergoes regioselective electrophilic bromination with NBS to give the 15-bromo analogue (MeO-BC-Br15) in 85% yield. By contrast, the bacteriochlorin lacking the 5-methoxy group (8,8,18,18-tetramethyl-2,12-di-p-tolylbacteriochlorin, H-BC) gives a mixture of two monobromo- and two dibromobacteriochlorins. Deuterium exchange of both bacteriochlorins (H-BC and MeO-BC) in acidic media (TFA-d) occurs preferentially at the beta-pyrrole positions (3, 13) > unhindered meso-positions (5, 15 for H-BC; 15 for MeO-BC) > hindered meso-positions (10, 20). The 15-bromo-5-methoxybacteriochlorin MeO-BC-Br15 was subjected to three types of Pd-mediated coupling reactions (Suzuki, Sonogashira, Hartwig-Buchwald) to give six bacteriochlorins bearing functional groups at the 15-position (49% to 85% yield). The groups include 4-(tert-butoxycarbonylmethoxy)phenyl, 4-pyridyl, 3,5-diformylphenyl, phenylethynyl, TIPS-ethynyl, and N-benzamido. The presence of the 15-ethynyl moiety shifts the position of the long-wavelength Qy band from 732 nm to approximately 753 nm. The ability to introduce a range of groups at a specific site enables synthetic bacteriochlorins to be tailored for a variety of applications.

Dimethylformamide, Dimethylacetamide and Tetramethylguanidine as Nucleophilic Organocatalysts for the Transfer of Electrophilic Bromine from N‐Bromosuccinimide to Alkenes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Competing kinetic pathways in the bromine addition to allylic ethers in 1,2‐dichloroethane: Opposite temperature effects

AbstractThe kinetics of the electrophilic bromination of three allylic ethers in a nonprotic solvent, 1,2‐dichloroethane, has been investigated. Two of them followed a prevalent second‐order pathway, while the third one exhibited a classical, clean third order. The second‐order pathway in the first two olefins is attributed to electrophilic assistance of the ethereal oxygen to the attacking bromine molecule. In the molecular bromination of 2,4‐cis‐dimethyl‐8‐oxabicyclo[3.2.1]‐6‐octen‐3‐cis‐ol, opposite temperature dependences were found for the two different kinetic pathways. An exoergonic process for the second‐order reaction was explained by the lesser stability of the bromiranium–bromide ionic intermediate, compared to the bromiranium–tribromide in the third‐order profile. © 2007 Wiley Periodicals, Inc. 39: 197–203, 2007

Synthesis and Biological Evaluation of [18F]Bicalutamide, 4-[76Br]Bromobicalutamide, and 4-[76Br]Bromo-thiobicalutamide as Non-Steroidal Androgens for Prostate Cancer Imaging

Androgen receptors (AR) are overexpressed in most primary and metastatic prostate cancers. To develop a nonsteroidal AR-mediated imaging agent, we synthesized and radiolabeled several analogs of the potent antiandrogen bicalutamide: [18F]bicalutamide, 4-[76Br]bromobicalutamide, and [76Br]bromo-thiobicalutamide. Two of these analogs, 4-[76Br]bromobicalutamide and [76Br]bromo-thiobicalutamide, were found to have a substantially increased affinity for the androgen receptor (AR) compared to that of bicalutamide. The synthesis of [18F]bicalutamide utilized a pseudocarrier approach to effect addition of a carbanion generated from tracer-level amounts of a radiolabeled precursor to an unlabeled carbonyl precursor. 4-[76Br]Bromobicalutamide and [76Br]bromo-thiobicalutamide were labeled through electrophilic bromination of a tributylstannane precursor. The former could be prepared in high specific activity, and its tissue distribution was tested in vivo. Androgen target tissue uptake was evident in castrated adult male rats; however, in DES-treated, AR-positive, tumor-bearing male mice, tumor uptake was low.

Dimethylformamide, dimethylacetamide and tetramethylguanidine as nucleophilic organocatalysts for the transfer of electrophilic bromine from N-bromosuccinimide to alkenes

Dimethylformamide, dimethylacetamide and tetramethylguanidine were found to act as increasingly active catalysts for the bromolactonisation of γ,δ- and δ,ε-unsaturated carboxylic acids with N-bromosuccinimide. The catalysts are readily removed in the work-up by washing with water to provide the pure bromolactone products without the need for column chromatography. Catalysis of the intermolecular bromoacetoxylation of alkenes with acetic acid and NBS by TMG was also demonstrated.

A Hypothesis Concerning the Biosynthesis of the Obtusallene Family of Marine Natural Products via Electrophilic Bromination

[Structure: see text] A hypothesis concerning the biosynthesis of the marine natural product family the obtusallenes is proposed. Multiple electrophilic bromination events are invoked.

Bromoiodinanes with an I(III)—Br Bond: Preparation, X‐Ray Crystallography and Reactivity as Electrophilic Brominating Agents.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Novel Derivatives of the Benzo[b][1,6]naphthyridine System.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Novel derivatives of the benzo[b][1,6]naphthyridine system

An efficient synthesis of 2-hydroxy-6-methylbenzo[b][1,6]naphthyridin-1(2H)-one was devised. The hydroxy group was alkylated, acylated and replaced by hydrogen. Electrophilic nitration, bromination and chlorosulfonation occurred readily in the 4-position. From the last, various sulfonamide derivatives were prepared. A selection of the products was screened by the National Cancer Institute. Cytotoxicities were generally low.

High Temperature Bromination of Benzobicyclo[2.2.2]Octa-2,5-Diene Derivatives: Alternative Synthesis of Di-, Tri- and Tetra-Bromobenzobarrelenes

The electrophilic bromination of benzobarrelene derivatives has been studied and alternative synthetic methods developed for, di-, tri- and tetrabromobenzobarrelenes.

Bromoiodinanes with an I(iii)–Br bond: preparation, X-ray crystallography and reactivity as electrophilic brominating agents

Bromoiodinanes--conveniently and directly prepared from iodobenzenecarbinols and N-bromosuccinimide, and characterised for the first time crystallographically--act as electrophilic bromine donors.

Ortho-substituted iodobenzenes as novel organocatalysts for bromination of alkenes

Suitably ortho-substituted iodobenzenes act as organocatalysts for the transfer of electrophilic bromine from N-bromosuccinimide to alkenes via the intermediacy of bromoiodinanes.