Radical brominations chemoselectivity

The first step constitutes a che mo selective radical bromination of the methyl group in quinoline 10 using A-bromosuccinimide (33), leading to compound 34. Here benzoyl peroxide (32) acts as the radical initiator. A rule of thumb for chemoselectivity states that heat and light produce side-chain halogenation, whereas cold and catalysis favor halogenation of the aromatic nucleus. 

Let us go back to radical brominations (cf. Section. 1.7.3). The bromination of alkyl aromatics takes place completely regioselectively only the benzylic position is bromi-nated. The intermediates are the most stable radicals that are available from alkyl aromatics, namely, benzylic radicals. Refluxing orf/zo-xylene reacts with 2 equiv. of bromine to give one monosubstitution per benzylic position. The same transformation occurs when the reactants are irradiated at room temperature in a 1 2 ratio (Figure 1.22, right). The rule of thumb SSS applies to the reaction conditions that afford these benzylic substitutions chemoselectively. SSS stands for searing heat + sunlight —> side chain substitution. ... 

Tanko, J. M., Mas, R. H., Suleman, N. K. (1990). Stereoelectronic Effects on Chemoselectivity in the Free Radical Bromination of Arylcyclopropanes. Journal of American Chemical Society, 112, 5557-5562. 

Fig. 1.22. Competing chemoselectivities during the reaction of bromine with ort/zo-xylene by a polar mechanism (left) and a radical mechanism (right).

In some cases, chemoselectivity of side-chain reactions can be controlled by the reaction conditions, for example, in the bromination of 4,5-dimethylpyrimidine [252]. Bromination under ionic conditions (Br2 in HOAc) favors substitution at the 4-methyl group, but under radical conditions (N-bromosuccinimide (NBS) in CCI4), the 5-methyl group is preferentially substituted ... 

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