Bromination intermediates

The Markovnikov regioselectivity of the gem-alkenes is associated with a chemoselectivity. in favour of methanol attack, significantly greater than that observed for the other alkenes. If no sodium bromide is added to the reaction medium, no dibromide is observed for this series. Therefore, these alkenes behave as highly conjugated olefins, as regards their regio- and chemo-selectivity. In other words, the bromination intermediates of gem-alkenes resemble P-bromocarbocations, rather than bromonium ions. Theoretical calculations (ref. 8) but not kinetic data (ref. 14) support this conclusion. 

It has been shown (ref. 21) that a solvent which is both protic and nucleophilic, assists the formation of the bromination intermediates of moderately reactive olefins as styrenes in two ways, (Scheme 7). Firstly, the solvent initiates bromide ion formation electrophilically and, secondly, favours... 

Most of these results have been obtained in methanol but some of them can be extrapolated to other solvents, if the following solvent effects are considered. Bromine bridging has been shown to be hardly solvent-dependent.2 Therefore, the selectivities related to this feature of bromination intermediates do not significantly depend on the solvent. When the intermediates are carbocations, the stereoselectivity can vary (ref. 23) widely with the solvent (ref. 24), insofar as the conformational equilibrium of these cations is solvent-dependent. Nevertheless, this equilibration can be locked in a nucleophilic solvent when it nucleophilically assists the formation of the intermediate. Therefore, as exemplified in methylstyrene bromination, a carbocation can react 100 % stereoselectivity. 

In the absence of more elaborate methods of observing of short-lived bromination intermediates, the present results can provide some useful empirical rules, the most important being as follows. 

What is retained nowadays of the initial mechanism (Scheme 1) is the occurrence of a cationic intermediate. But bromine bridging is not general, and its magnitude depends mainly on the double bond substituents (Ruasse, 1990). For example, when these are strongly electron-donating, i.e. able to stabilize a positive charge better than bromine, / -bromocarbocations are the bromination intermediates. The flexibility of transition state and intermediate stabilization puts bromination between hydration via carbocations and sulfenylation via onium ions. 

Data on molecular structure of bromonium ions are sometimes extrapolated from that of the tribromide-adamantylideneadamantane bromonium ion pair [6] (Slebocka-Tilk et ai, 1985), the only stable ionic bromination intermediate that can be isolated and whose crystal structure has been determined. Since the first observation by Strating et al. (1969), it has been established that bromine addition to adamantylideneadamantane [5] in... 

If the formation of bromination intermediates is reversible, the experimental rate constants obtained by following bromine uptake are not those of the first ionization steps. It is therefore important to know whether return, shown to occur in halogenated media, can also occur in protic media, in which most of the kinetic data have been measured and structure- or solvent-reactivity relationships established. 

In protic solvents there is evidence that bromonium ions are formed reversibly when they are highly congested. In the absence of crowding, no experimental data support return but none exclude it either. When bromination intermediates are /f-bromocarbocations, it is highly improbable that they are formed reversibly, since the bromine atom bears no charge. 

The association of kinetics and stereochemistry is particularly useful for obtaining data on the structure, open or bridged depending on the substituents, of bromination intermediates. These short-lived reactive intermediates cannot be observed under the reaction conditions, but indirect kinetic methods enable us to determine the magnitude of bromine bridging on which the selectivity of product formation depends. 

Two UV filters (used to block UV-rays in sunscreens and other products), octyl-p-methoxycinnamate and octyl-dimethyl-p-aminobenzoate, reacted with chlorine, producing chlorine-substituted compounds as intermediates that finally cleaved to smaller ester products [121]. Some of the identified octyl-p-methoxycinnamate DBPs showed weak mutagenic properties. Chlorinated and brominated intermediates were formed during chlorination of 2-ethylhexyl-4-(dimethylamine)benzoate and 2-hydroxy-4-methoxybenzophenone, with trichloromethoxyphenol the most abundant DBP [122]. 

Henderson JP, Byun J, Williams MV, Mueller DM, McCormick ML, Heinecke JW (2001) Production of Brominating Intermediates by Myeloperoxidase. J Biol Chem 276 7867... 

In the absence of an organic halogen acceptor, the oxidized bromine intermediate is reduced by a second equivalent of dihydrogen peroxide, producing bromide and dioxygen [52]. The net reaction is the disproportionation of dihydrogen peroxide to dioxygen and water... 

The cyclic enol ethers 76 either form 1-alkoxy furans 77 by elimination44,1 or, more interestingly, they are oxidized by bromosuccinimide to brominated intermediates 78 which give a,J3-unsaturated y-oxoesters 79 after base treatment45). Reaction of the cyclic orthoesters 76 with LiAlH4 leads to y-oxoaldehydes 80 or their acetals 81 depending on the work-up procedure 46). 

Henderson, J. P, J. Byun, M. V. Williams, D. M. Mueller, M. L. McCormick, and J. W. Heinecke. 2001. Production of brominating intermediates by myeloperoxidase. A tran-shalogenation pathway for generating mutagenic nucleobases during inflammation. JBiolChem 276(11) 7867-75. 

A major new facility for the manufacture of bromine intermediates such as tetrabromobisphenol A was developed in 2000-2002 in Safi, Jordan by the Jordan Bromine Company Ltd., a joint ventiue between an Albemarle subsidiary, the Arab Potash Company Ltd. and the Jordan Dead Sea Industries Company Ltd. 

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