Electrophilic Bromination Research Articles

A new approach to the reduction of sulfoxides to sulfides with 1,3-dithiane in the presence of electrophilic bromine as catalyst.

A new, mild, and novel method is described for the efficient deoxygenation of sulfoxides to their corresponding sulfides with 1,3-dithiane at room temperature in the presence of catalytic amounts of N-bromosuccinimide (NBS), 2,4,4,6-tetrabromo-2,5-cyclohexadienone (TABCO), or Br(2) as the source of electrophilic bromine.

The preorganization step in organic reaction mechanisms. Charge-transfer complexes as precursors to electrophilic aromatic substitutions.

Metastable (pre-reactive) intermediates, as commonplace transients in simple bimolecular reactions, are usually unobserved (and ignored)-though they provide vital mechanistic insight. Thus, the preequilibrium (charge-transfer) complexes of various aromatic donors with rather typical electron acceptors such as Br(2), NO(+), and NO(2)(+) are examined quantitatively (via their molecular and electronic structures) to reveal surprisingly unorthodox aspects of what is conventionally referred to in organic chemistry textbooks as electrophilic aromatic bromination, nitrosation, and nitration, respectively.

The Electrophilic Bromination of Toluene: Determination of the Ortho, Meta, and Para Ratios by Quantitative FTIR Spectrometry

The bromination of toluene is used to illustrate the principles of electrophilic aromatic substitution. The products of the microscale synthesis are analyzed using quantitative IR spectroscopy. The experiment is simple to carry out and gives an accurate analysis of the ortho-, meta-, and para-bromotoluenes in the product mixture. The relative reactivities of the ortho, meta, and para protons can also be calculated.

Ring fluorinated thiophenes: applications to liquid crystal synthesis

Ring fluorinated thiophenes were synthesized via a Balz–Schiemann fluorination approach and were successfully employed in the synthesis of liquid crystals using regioselective electrophilic bromination and regioselective Suzuki coupling chemistry.

The effect of zinc–bromine interactions on electrophilic bromination in concentrated ZnBr 2 solutions

Facile bromination can be carried out in concentrated solutions of zinc bromide (60–80% w/w ZnBr 2 in water) [A. Ewenson, D. Itzhak, M. Freiberg-Bergstein, A. Shushan, B. Croitoru, D. Beneish, N. Faza, WO patent 99/19275, Bromine Compounds Ltd., Israel, 1999]. These brine solutions offer an alternative to expensive and harmful organic solvents. A correlation between the reactivity and the molecular ratio H 2O:Zn has been found and quantified using UV-Vis spectroscopy [J.A. Duffy, G.L. Wood, J. Chem. Soc., Dalton Trans. (1987) 1485; E. Eyal, A. Treinin, J. Am. Chem. Soc. 86 (1964) 4287–4290; D. Meyerstein, A. Treinin, Trans. Faraday Soc. 59 (1963) 1114–1120]. Based on spectrophotometric and NMR results, it is proposed that these concentrated aqueous solutions, which behave similarly to anhydrous media, enhance the reactivity of molecular bromine by polarizing the Br–Br bond. Furthermore they affect the electron density distribution in the organic substrates.

Use of WO(4)(2-) on layered double hydroxides for mild oxidative bromination and bromide-assisted epoxidation with H(2)O(2).

Tungstate, exchanged on a (Ni,Al) layered double hydroxide, is applied as a heterogeneous catalyst in the oxidation of bromide with H(2)O(2) and the ensuing electrophilic bromination of olefins. The high halogenation activity of the catalyst in essentially neutral conditions mimicks the activity of V-bromoperoxidase enzymes. In water, aromatic and aliphatic olefins are selectively converted to bromohydrins; in methanol, methoxybromides are produced. In appropriate solvent conditions, the bromohydroxylation of geminally di-, tri-, and tetrasubstituted olefins proceeds via dehydrobromination to the epoxide. Evidence for this mechanism is provided by kinetic and labeling experiments. This one-pot alternative for the two-step halohydrin epoxidation process is enabled by the mild pH conditions; bromide is effective in substoichiometric, catalytic amounts. All new catalytic procedures are characterized by a high oxidative stability of the catalyst, high productivity of the catalyst on weight basis, high W turnover frequencies in ambient conditions (up to 50 mol of product per W per h), and high chemo-, regio-, and stereoselectivities.

ChemInform Abstract: Rearrangement of Methylenecamphor During Electrophilic Bromination: Remarkably Clean Access to the Unnatural Fenchyl (1,3,3‐Trimethylbicyclo[2.2.1]heptane) System.

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Rearrangement of methylenecamphor during electrophilic bromination: remarkably clean access to the unnatural fenchyl (1,3,3-trimethylbicyclo[2.2.1]heptane) system

Treatment of (+)-methylenecamphor (2) with NBS in the presence of pyridine resulted in a rapid and remarkably clean rearrangement to yield a brominated (+)-methylenefenchone (3) in high yield and purity (>96%). The structure of the product was established by X-ray crystallography and the stereochemistry confirmed by both polarimetric and chiral GC analyses. Two transformations of the product were also performed to elucidate the structure.

Reactivity and selectivity of aryloxylium ions

The reactivity and selectivity of aryloxylium ions in acetonitrile–water mixtures are described. The 4-bromo-2,4,6-trialkylcyclohexa-2,5-dienones used as substrates were synthesised by electrophilic bromination in yields of 60% (3 R = Me) and 52% (7 R = But). Under solvolysis conditions 3 and 7 decompose cleanly via their respective aryloxylium cations to the 4-hydroxy-2,4,6-trialkylcyclohexa-2,5-dienones 4 and 12. As the polarity of the solvent increases, the observed rates of reaction increase by a factor of 36 (3) and 56 (7). A detailed study gave Grunwald–Winstein ms values of 0.56 (3) and 0.63 (7). Addition of sodium bromide caused a common ion rate depression with α = 22.1 (3) and α = 33.3 (7). Competitive azide trapping gave kaz ∶ kMeOH = 3610 and kMeOH ∶ kH2O = 0.755, while the lifetime of the cation 11 in water was estimated to be 0.55 µs. Sterically hindered alcohols (propan-2-ol, cyclohexanol) do not trap the aryloxylium ions, instead products of reduction (the corresponding phenols) were formed in quantitative yield. Following a careful search it was determined that these products did not arise from hydride transfer from these alcohols.

Noncovalent binding of the halogens to aromatic donors. Discrete structures of labile Br2 complexes with benzene and toluene

Precise molecular structures resulting from the noncovalent interaction of Br2 with benzene (and toluene) reveal the unusual localized bonding to specific (one or two) carbon centers in prereactive complexes leading directly to the transition states for electrophilic aromatic brominations.

ChemInform Abstract: Highly Efficient and Selective Electrophilic and Free Radical Catalytic Bromination Reactions of Simple Aromatic Compounds in the Presence of Reusable Zeolites.

Reactions of mono-substituted aromatics of moderate activity with bromine in the presence of stoichiometric amounts of zeolite NaY proceed in high yield and with high selectivity to the corresponding para-bromo products. The zeolites can easily be regenerated by heating and reused. Similar para-selectivity can be achieved in the case of toluene by use of tert-butyl hypobromite as reagent, zeolite HX as catalyst, and a solvent comprising a mixture of tetrachloromethane and diethyl ether. Radical bromination of ethyl 4-methylbenzoate using bromine in the presence of light is catalysed by various zeolites and affords a high yield of ethyl 4-(bromomethyl)benzoate but with no great improvement in selectivity for monobromination.

Substituent dependence of the diastereofacial selectivity in iodination and bromination of glycals and related cyclic enol ethers.

The stereochemical course of the electrophilic iodination and bromination of tri-O-benzyl-D-glucal under various conditions has been compared to that of substituted dihydropyrans 2-5. IN(3) addition in acetonitrile affords trans-alpha-iodoazides (80-87%), besides small amounts of trans-beta-adducts, in the presence or the absence of benzyloxy substituents at C-3 or C-4, and in agreement with bridged iodonium ion intermediates. In contrast, the diastereofacial selectivity of bromine addition in dichloroethane going through open bromo oxocarbenium ions depends strongly on the substituents. Whereas the trans-alpha-dibromides are the main (85-95%) adducts in the absence of C-4 and C-5 substituents, in their presence a moderate to exclusive selectivity for cis-alpha-addition (60-99%) is observed. The predominance of trans-alpha-addition is again observed whatever the substituents when the bromination is carried out in the same solvent but with a tribromide ion salt, supporting a concerted addition of the two bromine atoms under these conditions. Finally, bromine addition in methanol exhibits a completely different behavior with the nonselective formation of trans-alpha- and trans-beta-methoxybromides and a small dependence on the substituents. In agreement with the absence of azide trapping of any cationic intermediate, it is concluded that these brominations which do not go through an ionic intermediate are concerted additions of bromine and methanol with very loose rate- and product-determining transition states. Finally, the substituent conformation at C-4 influences drastically the stereoselectivity in all these brominations. Evidence for alpha-anomeric control of the nucleophile approach at C-1 is given by the highly predominant formation of alpha-adducts, except in the methanolic bromination. The factors determining the versatile selectivity of the electrophile approach are discussed in terms of PPFMO theory and of the special mechanisms of glycal reactions.

Measuring Relative Reactivities of Electrophilic Aromatic Bromination Using a Benchtop GC-MS

This laboratory provides students with the opportunity to reinforce their knowledge of the numerous parameters involved in electrophilic aromatic substitution reactions. These concepts are investigated using a benchtop GC:MS. Students obtain hands-on experience with the coupling of gas-chromatographic analysis and mass-spectral analysis. Each student determines one data point by reacting a pair of compounds with bromine and iron (ID) chloride. Individual results are then pooled into composite class data, affording students more available information for analysis than is typical in an organic chemistry laboratory.

Catalytic Enantioselective Chlorination and Bromination of β-Keto Esters

The Ti(TADDOLato) complexes dichloro[(4R,5R)-2,2-dimethyl-α,α,α′,α′-tetraphenyl-1,3-dioxolane-4,5-dimethanolato(2−)-O,O′]titanium ((R)-1a) and dichloro[(4R,5R)-2,2-dimethyl-α,α,α′,α′-tetra(naphthalen-1-yl)-1,3-dioxolane-4,5-dimethanolato(2−)-O,O′]titanium ((R)-1b) are efficient catalysts for the electrophilic enantioselective chlorination and bromination of β-keto esters with N-chlorosuccinimide (NCS) and N-bromosuccinimide (NBS), respectively. With 5 mol-% of catalyst at room temperature an enantioselectivity of up to 88% ee could be obtained for the chlorination reaction. Under comparable conditions, bromination reactions are slower and less stereoselective.

Nonplanar aromatic compounds. 3. A proposed new strategy for the synthesis of Buckybowls. Synthesis, structure and reactions of

A new strategy for the synthesis of Buckybowls is presented and initial attempts to implement it are reported. This involves annulation of further rings onto polycyclic aromatic systems that prefer to be planar but have been "pre-bent" by the installation of a tether. Pyrenophane 2b reacts with TCNE and PTAD to give 1:1 and 1:2 adducts, respectively. The less strained pyrenophane 2c is unreactive toward TCNE but gives a 1:2 adduct with PTAD. Attempted electrophilic aromatic brominations of pyrenophane 2e under a variety of conditions were unsuccessful, as were attempts to brominate cyclophanediene 1c, the direct synthetic precursor of 2c. Tether cleavage and addition reactions occurred rather than substitution. In an effort to circumvent tether cleavage problems, [7]-, [8]- and [9](2,7)pyrenophanes 22b-d were prepared. However, attempted bromination and Friedel-Crafts acylations failed. Evidence for the fleeting existence of [6](2,7)pyrenophane 22a was also obtained. Comparison of structural data (X-ray and AM1 calculations) for the pyrenophanes 22a-d with their 1,n-dioxa analogues 2a-d indicates that the nature of the tether has a strong effect on the degree of bend in the pyrene moiety and this led to the identification of trioxapyrenophane 28 as the next target in the quest for increasingly bent pyrenes.

Steric Strain and Reactivity: Electrophilic Bromination oftrans-(1-Methyl-2-adamantylidene)-1-methyladamantane

trans-(1-Methyl-2-adamantylidene)-1-methyladamantane (DMAD, 1b) reacts with Br(2) in chlorinated hydrocarbon solvents to give either a bromonium polybromide ion pair or a substitution product, depending on bromine concentration. The first intermediate is a 1:1 pi-complex having K(f) = 1.85(0.19) x 10(3) M(-)(1) at 25 degrees C, which rapidly evolves to the bromonium tribromide ion pair. At high bromine concentration, which shifts all equilibria involving the counteranion of the ion pair intermediate toward the pentabromide species, this bromonium ion is stable and unable to further evolve into products. Temperature-dependent NMR spectra indicate chemical exchange of Br(+) between the sides of the plane containing the two carbons of the bromonium ion. At very low bromine concentration, no ionic intermediate is detected and the reaction rapidly yields a rearranged substitution product, identified as 10. Under these conditions the disappearance of the pi-complex follows a first-order rate law, and the observed rate constant increases with increasing olefin concentration, showing that product formation implies Br(-) as counteranion of the ionic intermediate, whose formation is a reversible process. A comparison of the results reported here for the bromination of 1b with those previously found for the parent olefin, adamantylideneadamantane (1a), shows that steric strain markedly affects the reactivity of the double bond.

Molecular Modeling and Nuclear Overhauser Enhancement Spectroscopy (NOESY): Tools for Studying the Regioselective Bromination of 3-Bromoanisole

The use of molecular modeling for predicting chemical reactivity has been highly successful in the industrial and academic research communities. For this reason, increased emphasis has been placed on molecular modeling in the undergraduate curriculum. In the described experiment, the bromination of 3-bromoanisole, students are encouraged to use molecular modeling software as a tool for predicting chemical reactivity. Besides introducing students to molecular modeling, this experiment incorporates the use of nontraditional, less hazardous reagents and solvents for electrophilic aromatic bromination reactions. Lastly, nuclear Overhauser enhancement spectroscopy (NOESY) is introduced as a tool for structural elucidation. Although there are a number of aspects to this experiment, two 3-hour laboratory periods are sufficient because the results from semiempirical (AMI) geometry optimizations, which are complete in seconds, were almost identical to the higher order, more time-intensive ab initio (3-21G*) calculations. In addition, the experimental time was greatly shortened by the discovery that catalytic HCl(aq) reduces the reaction time from 5 hours to 18 minutes.

Highly efficient and selective electrophilic and free radical catalytic bromination reactions of simple aromatic compounds in the presence of reusable zeolites

Reactions of mono-substituted aromatics of moderate activity with bromine in the presence of stoichiometric amounts of zeolite NaY proceed in high yield and with high selectivity to the corresponding para-bromo products. The zeolites can easily be regenerated by heating and reused. Similar para-selectivity can be achieved in the case of toluene by use of tert-butyl hypobromite as reagent, zeolite HX as catalyst, and a solvent comprising a mixture of tetrachloromethane and diethyl ether. Radical bromination of ethyl 4-methylbenzoate using bromine in the presence of light is catalysed by various zeolites and affords a high yield of ethyl 4-(bromomethyl)benzoate but with no great improvement in selectivity for monobromination.

A Convenient Preparation Of Jv-Bromo-Saccharin, Source Of Electrophilic Bromine

An extremely straightforward, high yield synthesis of a very reactive electrophilic brominating reagentiV-bromosaccharin is described, allowing its preparation in multi-gram quantities and in high purity.

Spectroscopic and Theoretical Investigations of Electrophilic Bromination Reactions of Alkynes: The First Evidence for π Complexes as Reaction Intermediates

The first direct detection of a 1:1 Br2–alkyne complex as an intermediate during the addition of Br2 to alkynes is reported. The measured negative apparent activation energies for bromination of arylalkylacetylenes are only compatible with the formation of a reactive complex that precedes the rate-determining step. Quantum-chemical calculations suggest that the Br2 in the 1:1 complex functions as a donor for a second Br2 molecule as depicted here, giving a trimolecular complex structurally very similar to a stable Br2–Br2–alkene adduct reported some time ago.