Benzylic position bromination

Halogenation (Section 11 12) Free radical halo genation of alkylbenzenes is highly selective for substitution at the benzylic position In the exam pie shown elemental bromine was used Alterna Lively N bromosuccinimide is a convenient re agent for benzylic bromination... 

Side-chain bromination at the benzylic position occurs when an alkylbenzene is treated with /V-bromosuccinimide (NBS). For example, propylbenzene gives (l-bromopropyl)benzene in 97% yield on reaction tvith NBS in the presence of benzoyl peroxide, (PhC02)2f as a radical initiator. Bromination occurs exclusively in the benzylic position and does not give a mixture of products. 

The benzylic position of an alkylbcnzene can be brominated by reaction with jV-bromosuccinimide, and the entire side chain can be degraded to a carboxyl group by oxidation with aqueous KMnCfy Although aromatic rings are less reactive than isolated alkene double bonds, they can be reduced to cyclohexanes by hydrogenation over a platinum or rhodium catalyst. In addition, aryl alkyl ketones are reduced to alkylbenzenes by hydrogenation over a platinum catalyst. 

The positive bromination of aromatics ethers was first studied by Bradfield et al.193 and by Branch and Jones194. The reaction of hypobromous acid in 75 % aqueous acetic acid with benzyl 4-nitrophenyl ether and 4-nitrophenetole at 20 °C was very rapid and approximately second-order193. The value of k2/[H+] remained constant in the [H+] range 0.005-0.090 M for the effect of added mineral acids on the bromination of 4-nitroanisole and 4-nitrophenetole (at 19.8 °C)194. The variation in reaction rate with the percentage of acetic acid in the medium was also studied and showed a large increase in the 0-10 % range with a levelling off at approximately 25 % acetic acid (Table 52) this was attributed... 

The bromine atom is much more selective than the chlorine atom. As indicated on page 906, it is often possible to brominate tertiary and benzylic positions selectively. High regioselectivity can also be obtained where the neighboring-group mechanism (p. 899) can operate. 

Al-Bromosuccinimide is also a highly regioselective brominating agent at other positions, including positions a to a carbonyl group, to a C=C triple bond, and to an aromatic ring (benzylic position). When both a double and a triple bond are in the same molecule, the preferred position is a to the triple bond. ... 

Ethyl-l,2,3-thiadiazole 44 is readily brominated at its pseudo benzylic position and subsequent elimination afforded the vinyl thiadiazole 45 (Scheme 5) <1986LA1334, 1986LA1344>. To prevent polymerization of the vinyl thiadiazole, hydroquinone was added during the elimination step. 

Anodic oxidation of j9-methylbenzyl-sulfonic ester, -carboxylic ester, and -nitrile in Et3N-3HF/CH3CN affords fluorides and acetamides at tbe metbyl (Me) and substituted (CH2E) benzyl position Me/CH2E = 24/76 (E = C02Et), 9/91(CN), 69/31 (SOsEt). In tbe radical bromination of these compounds, substitution at CH3 is enhanced [20],... 

Bromination occurs exclusively at the benzylic position, i.e. adjacent to the benzene ring. The radical formed at this position is resonance stabilized, whereas no such stabilization is available to the primary radical formed by abstraction of one of the methyl hydrogens. 

A = Br3, BrCl2, IC12) [Sket and Zupan, 1984], An ethylene-A-bromomaleimide copolymer has been used for bromine substitution at allylic and benzyl positions [Yaroslavsky et al., 1970],... 

Side-Chain Chlorination of Arylalkanes. Alkyl-substituted aromatic compounds can easily be halogenated at the benzylic position with chlorine or bromine.107 108,142 143 a-Monohaloalkylaromatics are usually the main products with both reagents. 

The novel linker was produced by cesium carbonate activated coupling of commercially available syringaldehyde to Merrifield resin, under microwave heating conditions. Subsequently, the aldehyde moiety was reduced at room temperature within 12 h and the benzylic position was finally brominated by treatment with a large excess of thionyl bromide (10 equiv) leading to the desired polymeric support (Scheme 7.44). 

Direct introduction of a vinyl substituent onto an aromatic ring is not a feasible reaction. p-Methoxystyrene must be prepared in an indirect way by adding an ethyl side chain and then taking advantage of the reactivity of the benzylic position by bromination (e.g., with N-bromosuccinimide) and dehydrohalogenation. 

Free-radical bromination of toluene is selective for the benzylic position. Benzyl bromide cannot undergo elimination, and so nucleophilic substitution of bromide by hydroxide will work well. 

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 brominated. The intermediates are the most stable radicals that are available from alkyl aromatics, namely, benzylic radicals. Refluxing ortho-xylene reacts with 2 equiv. of bromine to give one monosubstitution... 

Hydrogen atoms in the benzylic position can be replaced by elemental bromine as shown. This is not true for hydrogen atoms in the allylic position. The alkene reacts rapidly with molecular bromine via addition and allylic bromination is not observed (Figure 1.25, left). A chemoselective allylic bromination of alkenes succeeds only according to the Wohl-Ziegler process (Figure 1.25, right), that is, with A-bromosuccinimide (NBS). 

Cerium(IV) ammonium nitrate (CAN) in acetic acid oxidizes potassium bromide and, consequently, brominates methylbenzenes at a benzylic position with 50-80% yield293. f-Butyl hydroperoxide (TBHP) oxidizes CuBr2 which a-brominates toluenes to benzyl... 

Another reagent that is quite useful in substituting bromine for hydrogen at allylic and benzylic positions is /V-bromosuccinimide (NBS) ... 

Free-radical bromination of the following compound introduces bromine primarily at the benzylic position next to the aromatic ring. If the reaction stops at the monobromination stage, two stereoisomers result. 

NBS also works well for brominating benzylic positions, next to an aromatic ring (see Problem 6-10). Allylic and benzylic halogenations are discussed in more detail in Chapter 15. 

Bromine radicals are not as reactive as chlorine radicals, so bromination is more selective than chlorination (Section 4-13C). Bromine reacts exclusively at the benzylic position. 

All of these syntheses involve NBS bromination of the benzylic position of a side chain. 

The substitution of a hydrogen atom in the benzylic position by a bromine atom on reaction with N-bromosuccinimide in the presence of catalytic amounts of AIBN (2.37) is known as the Wohl-Ziegler process k... 

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