Free-Radical Allylic Bromination

Propagation Each step consumes a radical and forms another radical leading to products. 

First Propagation Step The bromine radical abstracts an allylic hydrogen to produce an allylic radical. H H 

Second Propagation Step The allylic radical in turn reacts with a bromine molecule to form an allyl bromide and a new 

Regeneration of Br- NBS reacts with HBr to regenerate the molecule of bromine used in the allylic bromination step. 

Stability of Allylic Radicals Why is it that (in the first propagation step) a bromine radical abstracts only an allylic hydrogen atom, and not one from another secondary site Abstraction of allylic hydrogens is preferred because the allylic free radical that results is resonance-stabilized. The bond-dissociation enthalpies required to generate several free radicals are compared next. Notice that the allyl 

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The following propagation steps show how a mixture of products results from the free-radical allylic bromination of but-l-ene. 

Hydrogen bromide continually forms in the reaction. As its concentration increases, might it not add to the double bond in competition with the free-radical allylic bromination The answer is, it could if it was to accumulate as a reaction product. However, this possibility can be bypassed completely. We can use a reagent called N-bromosuccinimide (NBS) to carry out allylic bromination. NBS generates a low concentration of bromine and also prevents the continued production of HBr that would add to the double bond in an electrophihc addition reaction. 

Formation of isomers in free-radical allylic substitution is a general rule. In this case, abstraction of a hydrogen atom from C4 of the parent molecule leads to the formation of a delocalized allylic radical, with spin density distributed between two carbon atoms C-4 and C-6. Then this radical abstracts the bromine atom from NBS and adds it to one or the other position (Fig. 8) ... 

O-Deprotection. Free-radical-initiated bromination followed by treatment with water removes a benzyl ester. A similar method is also effective to cleave allyl ethers. Regioselective oxidations. An alkane-1,2-diol can be selectively oxidized to give the ketol (instead of the hydroxy aldehyde) via NBS reaction of the dibutylstan-nylene acetal. ... 

Bromination appears to involve substitution rather than addition. Baldwin and Kuntz (I960) report that bromination of butyl rubber with elemental bromine is accompanied by the formation of large amounts of HBr. Using ozonolysis techniques it was found that unsaturation did not greatly change with bromination. It has thus been inferred (Makowski, 1%9) that the reaction proceeds by a free radical allylic substitution rather than by an ionic mechanism, e.g. 

Bromination with A-bromosuccinimide generally gives the same result as bromination with free bromine or hypobromous acid. The reaction is considered to proceed with a small concentration of free bromine and does not generate an appreciable concentration of acid. Conditions are therefore mild. In addition, A-bromosuccinimide has been used to brominate the allylic position of a, -unsaturated ketones in the presence of free-radical promoters or with irradiation, and thus gives access to dienones by dehydro-halogenation, for exaraple " ... 

As we saw when discussing allylic bromination in Section 10.4, A-bromosuccin-imide (NBS) is a convenient free-radical brominating agent. Benzylic brominations with NBS are nonnally perfonned in carbon tetrachloride as the solvent in the presence of peroxides, which are added as initiators. As the exanple illustrates, free-radical bromination is selective for substitution of benzylic hydrogens. 

The allylic bromination of an olefin with NBS proceeds by a free-radical chain mechanism. The chain reaction initiated by thermal decomposition of a free-radical initiator substance that is added to the reaction mixture in small amounts. The decomposing free-radical initiator generates reactive bromine radicals by reaction with the N-bromosuccinimide. A bromine radical abstracts an allylic hydrogen atom from the olefinic subsfrate to give hydrogen bromide and an allylic radical 3 ... 

As mentioned in an earlier section (cf. Chapter 1, Section III), allylic positions are subject to attack by free radicals resulting in the formation of stable allyl radicals. A-Bromosuccinimide (NBS) in the presence of free-radical initiators liberates bromine radicals and initiates a chain reaction bromination sequence by the abstraction of allylic or benzylic hydrogens. Since NBS is also conveniently handled, and since it is unreactive toward a variety of other functional groups, it is usually the reagent of choice for allylic or benzylic brominations (7). 

That the mechanism of allylic bromination is of the free-radical type was demonstrated by Dauben and McCoy, who showed that the reaction is veiy sensitive to free-radical initiators and inhibitors and indeed does not proceed at all unless at least a trace of initiator is present. Subsequent work indicated that the species that actually abstracts hydrogen from the substrate is the bromine atom. The reaction is initiated by small amounts of Br. Once it is formed, the main propagation steps are... 

The mechanism is usually electrophilic (see p. 972), but when free-radical initiators (or UV light) are present, addition can occur by a free-radical mechanism. Once Br-or Cl- radicals are formed, however, substitution may compete (14-1 and 14-2). This is espiecially important when the alkene has allylic hydrogens. Under free-radical conditions (UV light) bromine or chlorine adds to the benzene ring to give, respectively, hexabromo- and hexachlorocyclohexane. These are mixtures of stereoisomers (see p. 161). ... 

That the mechanism of bromination by NBS was a free radical one was first suggested by Goldfinger et al (1953, 1956) and later supported by Dauben and Me Coy in 1959 and also by Tedder et al in 1960 and 1961. The strongest point in favour of the reaction being a free radical one is that it is catalysed by free radical initiators like peroxides and is also promoted by light. Indeed new substitution at the allyl position is often used to detect free radicals. Like free radical reactions, it is also retarded by inhibitors. 

Wohl in 1919 reported that A -bromoacetamide (CH CONHBr) induced allylic bromination. " Then iV-bromosuccinimide (30) was described in 1942 by Ziegler and co-workers to be useful in such free radical bromination reactions (equation 41), " and this widely utilized procedure is known as the Wohl-Ziegler reaction. In 1963 the mechanism of the reaction was proposed to involve halogen atoms in the hydrogen abstraction step " " " instead of succinimidyl radicals as had been commonly supposed. The halogen atom mechanism had previously been proposed by Gosselain et al. for reactions of yV-chlorosuccinimide. " ... 

Problem 8.43 CH3CH==CH2 is subjected to allylic free-radical bromination. Will the reaction product be exclusively labeled H C = CH CHjBr Explain. ... 

In gas-phase hydrobromination, where a radical mechanism is operative, the bromine atom always adds to the central carbon atom of the allenic system. As a result, vinylic bromides are formed through the stable allylic radical. In the solution phase under ionic addition conditions, either the vinylic or the allylic cation may be the intermediate, resulting in nonselective hydrobromination. Allylic rearrangement or free-radical processes may also affect product distributions. 

The propagation steps are analogous to those of other free-radical brominations. An allylic hydrogen is removed by a bromine atom in the first step. 

Although free-radical halogenation is a poor synthetic method in most cases, free-radical bromination of alkenes can be carried out in a highly selective manner. An allylic position is a carbon atom next to a carbon-carbon double bond. Allylic intermediates (cations, radicals, and anions) are stabilized by resonance with the double bond, allowing the charge or radical to be delocalized. The following bond dissociation enthalpies show that less energy is required to form a resonance-stabilized primary allylic radical than a typical secondary radical. 

The mechanism is similar to other free-radical halogenations. A bromine radical abstracts an allylic hydrogen atom to give a resonance-stabilized allylic radical. This radical reacts with Br2, regenerating a bromine radical that continues the chain reaction. 

For efficient allylic bromination, a large concentration of bromine must be avoided because bromine can also add to the double bond (Chapter 8). A-Bromosuccimnude (NBS) is often used as the bromine source in free-radical brominations because it combines with the HBr side product to regenerate a constant low concentration of bromine. No additional bromine is needed because most samples of NBS contain traces of Br2 to initiate the reaction. 

Like allylic cations, allylic radicals are stabilized by resonance delocalization. For example, Mechanism 15-2 shows the mechanism of free-radical bromination of cyclohexene. Substitution occurs entirely at the allylic position, where abstraction of a hydrogen gives a resonance-stabilized allylic radical as the intermediate. 

An important question now arises here. If bromine is the reacting species why does it not react with the double bond either by ionic or free radical mechanism The answer is that its concentration is too low and this slows the rate of addition and in the circumstances only allylic substitution successfully takes place. This means that if there is regular, slow and steady supply of bromine and if somehow HBr formed, be removed to check addition, then it should be possible to brominate an olefine in allylic position even in absence of NBS and this has been demonstrated by Tedder et al. 

A further useful application of SC-CO2 as a reaction medium is the free-radical side-chain bromination of alkylaromatics, replacing conventional solvents such as tetra-chloromethane or chlorofluorohydrocarbons having no abstractable hydrogen atoms [920]. For example, bromination of ethylbenzene in SC-CO2 at 40 °C and 22.9 MPa yields 95 cmol/mol (1-bromoethyl)benzene, with practically the same regioselectivity as obtained in conventional tetrachloromethane as the solvent. Even the classical Wohl-Ziegler bromination of benzylic or allylic substrates using A-bromosuccinimide (NBS) can be conducted in SC-CO2 [920]. Irradiation of a solution of toluene, NBS, and AIBN (as initiator) in SC-CO2 at 40 °C and 17.0 MPa for 4 hours gave (bromomethyl)-... 

The mechanism of the allylic Wohl-Ziegler bromination involves free radicals, as shown in Scheme 2.36. 

Bromination with a free-radical brominating agent such as A-bromo-succinimide (3.6) takes place at the allylic position. The radical that is formed in the first step of the reaction is delocalized, and hence the final product may be a mixture (Scheme 3.24). 

Under standard conditions (N-bromosuccinimide [NBS] and AIBN [azo-bis(isobutyronitrile)] in refluxing CCI4), the desired brominated poly(TMSP) products were formed in high yield. Nearly quantitative yields were obtained up to bromination levels of 50%, on the basis of one Br substitution per monomer unit, but unexpectedly, the maximum attainable bromination level was only 60%, even when a large excess of NBS was used (Table I). We attributed this curious behavior to the extreme steric crowding at the allylic methyl groups in the polymer structure. The accessibility of the allylic sites apparently is so limited that monobromination is the exclusive reaction, and the presence of the bulky halogen decreases the likelihood of bromination at adjacent allylic sites. Similar results were obtained when benzoyl peroxide was used as the free-radical source. 

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