Bromination-debromination

Ionic reactions of neutral substrates can show large solvent dependence, due to the differential solvent stabilization of the ionic intermediates and their associated dipolar transition states (Reichardt, 1988). This is the case for the electrophilic addition of bromine to alkenes (Ruasse, 1990, 1992 Ruasse et al., 1991) and the bromination of phenol (Tee and Bennett, 1988a), both of which have Grunwald-Winstein m values approximately equal to 1 so that the reactions are very much slower in media less polar than water. Such processes, therefore, would be expected to be retarded or even inhibited by CDs for two reasons (a) the formation of complexes with the CD lowers the free concentrations of the reactants and (b) slower reaction within the microenvironment of the less polar CD cavity (if it were sterically possible). 

Contrary to the above expectations, the bromination of anisole (Tee and Bennett, 1984) and of phenols (Tee and Bennett, 1988a) in the presence of a-CD is not strongly retarded, so that some form of catalysis must occur. In some cases, actual rate increases are observed in spite of the several complexations that reduce the free reactant concentrations. Analysis of the effects of substituents on the kinetics leads to the conclusion that the catalysis by a-CD most probably results from reaction of CD-bound bromine with free substrate (12a) and that the a-CD-Br2 complex is 3-31 times more reactive than free Br2 towards phenols and phenoxide ions (cf. Tee et al., 1989). For the kinetically equivalent reaction of the substrate CD complex with free bromine (12b), the rate constants (A 2 ) for phenols do not correlate sensibly with the nature and position of the substituents, and for three of the phenoxide ions they have unrealistically high values, greater than 10u m 1 s . 

For reactions, such as phenol bromination, in which two substrates are required to produce the rate-limiting transition state the value of KTS may 

This approach has been applied (Tee, 1989) to kinetic data for the bromination of phenols and phenoxide ions catalysed by a-CD. For 15 different substrates (nine phenols and six phenoxides) Krs values vary only between 0.07 and 0.8 mM, with most being between 0.1 and 0.5 mM, indicating very similar transition state stabilization for substrates with a range of reactivity of 40 million (Table A4.2). Moreover, the values of Krs show no clear correlation with Ks- This lack of dependence of KTS on the structure of the substrate is strong evidence that the transition state for the catalysed process is one in which the phenol moiety is basically outside the CD cavity while the bromine is inside ([9]— [10]). The same conclusion was 

The debrominations of a series of 4-alkyl-4-bromo-2,5-cyclohexadienones (ipso-dienones [11]) were also studied and found to undergo strong catalysis by a-CD (Tee and Bennett, 1988b). These reactions were chosen for scrutiny since they should serve as good models for the reverse of the 

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Vilsmeier-Haack and Friedel-Crafts reactions, bromination, debromination, debenzylation in indole series and their synthetic application 99YZ35. 

It is known that pyridinium tribromide converts olefins with specific r/7 t/-dibromina-tion. Therefore, the v/c-dibromides thus obtained can be cathodically reduced to the original olefins without geometrical changes of molecular structure [218]. This stereospecific bromination-debromination may be useful as an olefin protection-deprotection method. 

A general method of synthesis of phosphole derivatives is illustrated by the preparation of l-phenoxy-3,4-diphenylphosphole 1-oxide (112) by a bromination-debromination sequence as shown. ... 

Halogen-mediated syntheses of oxazoles were also described for instance, the iterative bromination/debromination of 126 with NBS allowed a wide-scope, metal- and catalyst-free synthesis of oxazoles 127 (13EJ04554). 

Synthesis of [6]-annelated indoles by thermal electrocyclic reactions 95MI7. Transition metal-mediated syntheses of carbazole derivatives 95MI6. Vilsmeier-Haack and Friedel-Crafits reactions, bromination, debromination, debenzylation in indole series and their synthetic application 99YZ35. 

X0 group present in hecogenin (79) is transferred to C-11 (84). Bromination of hecogenin in ben2ene yields the lla,23a-dibromo derivative (80). The latter is treated with sodium hydroxide in aqueous /-butanol to yield the crystalline 23-bromo-ketal (81) which is acetylated and then debrominated with... 

Bromo-5-methylene-2(5//)-furanone 133 was obtained from the /3-angelica lactone 129 by using mild simple methods that combine bromination and dehy-drobromination or debromination processes accomplished in a convenient order, as illustrated in Scheme 41 (94T12457). 

In a modified procedure the free carboxylic acid is treated with a mixture of mercuric oxide and bromine in carbon tetrachloride the otherwise necessary purification of the silver salt is thereby avoided. This procedure has been used in the first synthesis of [1.1.1 ]propellane 10. Bicyclo[l.l.l]pentane-l,3-dicarboxylic acid 8 has been converted to the dibromide 9 by the modified Hunsdiecker reaction. Treatment of 9 with t-butyllithium then resulted in a debromination and formation of the central carbon-carbon bond thus generating the propellane 10." ... 

Benzodioxocin (14) can also be prepared starting from the dihydro derivative 17.14 Whereas an attempted bromination-didehydrobromination procedure was not successful, the required dehydrogenation was achieved by bromination with A -bromosuccinimide and treatment with triethylamine, by double bromination with iV-bromosuccinimide and debromination with zinc, or by pyrolysis of a diacetate derived from 17 by bishydroxylation and acetylation.14... 

Incineration of a collection of polymers with 10 different kinds of brominated flame retardants has been studied under standardized laboratory conditions using varying parameters including temperature and air flow. Polybrominated diphenyl ethers like the deca-, octa-, and pentabromo compounds yield a mixture of brominated dibenzofurans while burning in polymeric matrices. Besides cyclization, debromination/hydrogenation is observed. Influence of matrix effects and burning conditions on product pattern has been studied the relevant mechanisms have been proposed and the toxicological relevance is discussed. 

During incineration of 1 in the polymeric matrix debromination/hydrogenation occur in addition to cyclization process. Tetrabrominated dibenzofuran isomers are the most abundant products formed in the temperature range between 300° or 400° (Figure 6 shows Br-composition at 300° - 800°C). Incineration at 400°C gives tetrabromo-benzofurans in yields up to 13 % (Fig. 6). Besides of PBDF, brominated dibenzodioxins are also formed, but to a much lesser extent (30-90 ppm) (ref. 11). 

The debromination/hydrogenation reaction shows some stereospecificity. Bromine in lateral positions of C-2, C-3, C-6 and C-7 reacts faster than in the peri position (C-1, C-4, C-5, C-8). This is shown below for photolysis of 1,2,3,4,6,7-hexabromodibenzodioxin. 

Morris PJ, JF Quensen III, JM Tiedje, SA Boyd (1993) An assessment of the reductive debromination of poly-brominated biphenyls in the Pine River reservoir. Environ Sci Technol 27 1580-1586. 

In the case of deca-BDE, its suggested degradation process in mammals consists of a first reductive debromination where one, two or three bromine atoms can be replaced by hydrogen atoms followed by an oxidation to form hydroxylated metabolites, which are presumably formed from an intermediate epoxy [52]. This study detected traces of three nona-BDEs, which may be an indication of reductive debromination as a first step of degradation, and thirteen hydroxylated metabolites. Otherwise, the possibility of a deca-BDE oxidation as a first step to form the epoxy without an intermediate reductive debromination is also suggested [52]. The study conducted by Morck et al. [53] detected several hydroxylated products, from methoxy-hydroxy-pentabrominated to methoxy-hydroxy-heptabrominated compounds, which coincide with part of the metabolites obtained by Sandholm et al. [52]. In addition, both authors found that methoxy and hydroxy substituents are always on the same aromatic ring when both are present. Moreover,... 

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