Radical chain reaction allylic bromination

This allylic bromination with NBS is analogous to the alkane halogenation reaction discussed in the previous section and occurs by a radical chain reaction pathway. As in alkane halogenation, Br- radical abstracts an allylic hydrogen atom of the alkene, thereby forming an allylic radical plus HBr. This allylic radical then reacts with Br2 to yield the product and a Br- radical, which cycles back... 

The bromination of bicyclo[3.2.1]oct-2-ene (46) with A -bromosuccinimide under conditions which promote radical chain reactions (carbon tetrachloride as the solvent activation by UV light gave the expected allylic bromination product exo-4-bromobicyclo[3.2.1]oct-2-ene (47). On the other hand, when the related bicyclo[3.2.1]octa-2,6-diene (48) was treated with N-bro-mosuccinimide under comparable conditions (carbon tetrachloride as the solvent activation by benzoyl peroxide and visible light) no product 49 of allylic bromination was formed. Instead, the bromination resulted in the formation of ejco-6-bromotricyclo[3.2.1.0 ]oct-3-ene (50), due to participation of the C6 to C7 double bond in 48. - ... 

Anti-Markovnikov addition of HBr,18e induced by radical-formers or photo-chemically, is preparatively important.152 An olefin and atomic bromine can, by reactions (a) and (b) form the radials (3) and (4) respectively, of which (3) is usually the more stable. (3) reacts with HBr to give the anti-Markovnikov adduct, together with a new bromine atom (radical chain reaction). Thus in the presence of small amounts of oxygen or peroxide (added specifically or already present in old preparations), allyl bromide affords the abnormal (anti-Markovnikov) 1,3-dibromopropane within 30 minutes and Mayo and Waling153 have collected numerous other examples. 

Allylic bromination by NBS is a radical-chain reaction occurring on the surface of the NBS crystals. A solution of NBS in tetrachloroethane or nitro-methane adds bromide to a C=C group 354 solvents are therefore used in which NBS and, if possible, also the succinimide formed, are difficultly soluble dry CC14 is usually chosen, but for reactive substances cyclohexane or benzene may also be used. The more polarized the N-halogen is, i.e.9 the more positive the Br is rendered, the more easily does the A-halogenated compound cause addition to the C=C bond NBS is particularly suitable for allylic bromination because of its steric structure and the almost apolar nature of its N-Br bond. 

There are some instances where the chlorination or bromination reaction can be used to good effect, however. Alkenes that have allylic hydrogens can sometimes be halogenated specifically at an allylic position in a process called allylic halogenation, another free radical chain reaction. For example, when low concentrations of bromine are photolyzed in the presence of the complicated cyclohexene shown in Figure 11.51, the product is exclusively brominated in one allylic position. 

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 ... 

The chain propagation step consists of a reaction of allylic radical 3 with a bromine molecule to give the allylic bromide 2 and a bromine radical. The intermediate allylic radical 3 is stabilized by delocalization of the unpaired electron due to resonance (see below). A similar stabilizing effect due to resonance is also possible for benzylic radicals a benzylic bromination of appropriately substituted aromatic substrates is therefore possible, and proceeds in good yields. 

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). 

The mechanism of benzylic bromination is similar to that discussed in Section 10.4 for allylic bromination of alkenes. Abstraction of a benzylic hydrogen atom generates an intermediate benzylic radical, which reacts with Br2 to yield product and a Br- radical that cycles back into the reaction to carry on the chain. The Br2 necessary for reaction with the benzylic radical is produced by a concurrent reaction of HBr with NBS. 

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. 

Since both methyl groups are functionalized, the unstable A must have one Br on each methyl group. The peroxide produces benzoate radicals that abstract a proton from allylic positions to give stabilized radicals and these attack bromine molecules providing bromine atoms to continue the chain reaction. In base, the carboxylate ion cyclizes on to the cis CH2Br group. 

The first propagation step of the bromination radical chain is significantly endothermic. A small change in product radical stability is reflected in the barrier for reaction and consequently in the rate of reaction. Thus the first propagation step (and the chain reaction) that goes the fastest forms the most stable product radical. Bromination will select for allylic and benzylic > tertiary > secondary > primary > vinyl and phenyl. 

The reaction involves initial homolytic cleavage of the N—Br bond in NBS. This generates the bromine radical needed to initiate the radical reaction. Light or heat and a radical initiator such as a peroxide are used to promote the reaction. The bromine radical abstracts an allylic hydrogen to form HBr and an allylic radical. The allylic radical reacts with Br2, forming the allyl bromide and a chain-propagating bromine radical. 

The chemical properties of succinimidyl radicals remained a mystery until the simultaneous recognition in the laboratories of Professor J. G. Traynham (1 ) and ours (2) that the radical could be a chain carrier in the sense first suggested by Bloomfield O), albeit incorrectly ( ), for the allylic bromination reaction. 

The initiation step provides a radical source by thermal or photochemical dissociation of initiators, which then provides bromine radicals by reaction with Br2. Initiators are sometimes present in the alkene as allyl hydroperoxides which may be present due to inadvertent, prior autooxidation. Bromine or HBr may be present in trace amounts in NBS. Reaction of the bromine radical 20 with the substrate 1 proves selective for allylic or benzylic hydrogens due to the near thermoneutral nature of the reaction which breaks the C-H bond and forms the H-Br bond. Reaction of the formed carbon-centered radical 21 with Br2 provides the desired bromide 3 and Br 20. Hydrogen bromide 17 reacts with NBS to form succinimide 4 and resupplies the required low concentration of Br2. Alternatively, reaction of substrate radical 21 with NBS 2 provides product 3 and succinimidyl radical 22 (S ). Due to energy and kinetics considerations, abstraction of the allylic hydrogen by the S should be slower than abstraction of bromine from NBS by an allyl radical. In using solvents in which NBS, succinimide 4 or it s radical 22 are not very soluble, S is not the key chain-carrier. Byproducts and side-reactions can occur with S. ... 

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)-... 

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