Electrophilic Bromination Reagents

Electrophilic bromination (and nitration) of pyrido[l, 2-a]benzimidazole (analogous to 132) cannot take place in the imidazole moiety. Initial substitution, using NBS as reagent, was shown to occur at the 8-position, and subsequently at C-4 and C-6 (90JOU1166). 

Oxidation of sulphoxides to sulphones may be brought about by the use of several different bromine-containing reagents which act as a source of electrophilic bromine. To date, these reagents have not received the same attention as their chlorine analogues. 

As has been mentioned above, thermal decarboxylation of heterocycle 36 can be coupled with electrophilic trapping with either bromine or nitro groups to yield the substituted analogues. The same heterocyclic system 59 can be thiolated by treatment either with elemental sulfur (followed by alkylation with an alkyl halide) to afford 60, or the electrophilic thiolating reagent 58 to generate 57 (Scheme 5) <2005HCA1208>. 

A number of N-brominated and N-chlorinated heterocycles also provide sources of electrophilic bromine. Examples include 1-chlorobenzotriazole (82JOC4895 87JOC173 88CHE36) and various HBr and Br2 adducts of pyridines, or pyridine perbromides [84SC939 85JAP(K)60/87264], Polymer-supported reagents of this type include 1-cyclohexylpyridinium perbromide linked to polystyrene, effective for the bromination of 1-methylindole, benzo[fc]furan, and benzo[6]thiophene (89T7869). 

Electrophilic addition of the halogens and related X—Y reagents to alkenes and alkynes has been a standard procedure since the beginning of modem organic chemistry.1 Anti electrophilic bromination of such simple compounds as cyclohexene and ( )- and (Z)-2-butene, and variants of this reaction when water or methanol are solvents (formation of halohydrin or their methyl ethers, respectively), are frequently employed as prototype examples of stereospecific reactions in elementary courses in organic chemistry. A simple test for unsaturation involves addition of a dilute solution of bromine in CCU to the... 

Y-Chlorosaccharine748 and also TCCA749 are useful reagents for the chlorination of ketones. The regioselectivity in the electrophilic bromination of methyl ketones is strongly influenced by the presence of amides. Normally, the a-methylene group is brominated but, upon addition of urea, up to 80% of a-methyl bromination is obtained750. 

The bromine atom has replaced an atom of hydrogen and so this is a substitution reaction. The reagent is electrophilic bromine and the molecule is aromatic so the reaction is electrophilic aromatic substitution and that is the subject of this chapter. We can compare the bromination of cyclohexene and of benzene directly. 

AgSbF6/Cl2/CH2Cl2 at -IS to 4 3S C is reported to be a convenient and effective reagent for the electrophilic chlorination of tertiary alkanes and cycloalkanes. Adamantane was sufficiently reactive to undergo uncatalyzed electrophilic bromination at 80 Substrates with adjacent tertiary C—H bonds... 

Molecular bromine is normally used to prepare bromoketones, but some interesting results have been obtained by the use of cupric bromide in boiling tetrahydrofuran [153]. The reagent is remarkably selective and does not attack C=C double bonds. Its action may be to provide bromine at such low concentration as to permit selective bromination of enols under kinetic control. As an alternative, cupric bromide could conceivably act directly as a source of electrophilic bromine. 

The Reformatksy adduct (248), obtained from a pregn-16-en-20-one and a-bromoisobutyric ester (see p. 263), has the properties of an enolic ester. Electrophilic bromination affords 17-bromo-20-ketones(249), with C(17) stereochemistry surprisingly depending upon the reagent (CuBr2 in methanol — I7a-Br Br2 — 17)3-Br), as revealed by subsequent transformations. 

This analysis of the simple addition of an electrophilic bromine molecule to a symmetrical alkene or alkyne has highlighted many points. First, there is the induction of a temporary dipole of the soft electrophile by the n electrons of the carbon/carbon double bond. Second, there is the heterolytic fission of the bromine molecule, and the subsequent formation of the cyclic bromonium ion. Third, this cyclic intermediate places certain restrictions on the potential line of attack for the second reagent, and so controls the structural and stereochemical consequences for the product. 

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