Alkene allylic bromination

Preparing Alkyl Halides from Alkenes Allylic Bromination 339... 

PREPARING ALKYL HALIDES FROM ALKENES ALLYLIC BROMINATION... 

The fact that the bromine concentration remains at veiy low levels is important to the success of the allylic halogenation process. The allylic bromination of alkenes must... 

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... 

In addition to its effect on stability, delocalization of the unpaired electron in the allyl radical has other chemical consequences. Because the unpaired electron is delocalized over both ends of the nr orbital system, reaction with Br2 can occur at either end. As a result, allylic bromination of an unsymmetrical alkene often leads to a mixture of products. For example, bromination of 1-octene gives a mixture of 3-bromo-l-octene and l-bromo-2-octene. The two products are not formed in equal amounts, however, because the intermediate allylic radical is... 

Simple alkyl halides can be prepared by radical halogenation of alkanes, but mixtures of products usually result. The reactivity order of alkanes toward halogenation is identical to the stability order of radicals R3C- > R2CH- > RCH2-. Alkyl halides can also be prepared from alkenes by reaction with /V-bromo-succinimide (NBS) to give the product of allylic bromination. The NBS bromi-nation of alkenes takes place through an intermediate allylic radical, which is stabilized by resonance. 

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. 

Allylic bromination of unsymmetrical alkenes may give many products. Occasionally one product is formed in reasonable yield, e.g. (3), but this is a matter for trial and error. 

Novel results were reported for allylic bromination. In radical bromination of cyclohexene in CCI4 under light the selectivity of substitution over addition was shown to be controlled by bromine concentration.304 Substitution via the corresponding allyl radical, while relatively slow, is irreversible and fast enough to maintain the concentration of bromine at a sufficiently low level to prevent significant addition. The reaction of two strained alkenes, fZ)-1,2-dimethyl-1,2-di-ferf-butylethylene and the -isomer (14), leads to the corresponding bromosubstituted product, instead of addition 305... 

Allylic brominations are normally carried out using one of a number of specialized reagents developed for that purpose. /V-Bromosuccinimide (NBS) is the most frequently used of these reagents. An alkene is dissolved in carbon tetrachloride, /V-bromo-succinimide is added, and the reaction mixture is heated, illuminated with a sunlamp, or both. The products are an allylic halide and succinimide. 

Allylic bromination normally uses NBS as bromine itself would add to the alkene. Thus cyclohexene gives the dibromide 18 with Br2 but the allylic bromide with NBS. Bromine radicals abstract one of the marked H atoms from 19 and the intermediate allylic radical 21 is delocalised so we don t know which end of the allylic system5 ends up attached to Br. 

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). 

The other piece we need is an allylic bromide. Allylic bromides are formed by allylic bromination of alkenes (Section 6-6B). 

A thoughtful reader would have noticed that, while plenty of methods are available for the reductive transformation of functionalized moieties into the parent saturated fragments, we have not referred to the reverse synthetic transformations, namely oxidative transformations of the C-H bond in hydrocarbons. This is not a fortuitous omission. The point is that the introduction of functional substituents in an alkane fragment (in a real sequence, not in the course of retrosynthetic analysis) is a problem of formidable complexity. The nature of the difficulty is not the lack of appropriate reactions - they do exist, like the classical homolytic processes, chlorination, nitration, or oxidation. However, as is typical for organic molecules, there are many C-H bonds capable of participating in these reactions in an indiscriminate fashion and the result is a problem of selective functionalization at a chosen site of the saturated hydrocarbon. At the same time, it is comparatively easy to introduce, selectively, an additional functionality at the saturated center, provided some function is already present in the molecule. Examples of this type of non-isohypsic (oxidative) transformation are given by the allylic oxidation of alkenes by Se02 into respective a,/3-unsaturated aldehydes, or a-bromination of ketones or carboxylic acids, as well as allylic bromination of alkenes with NBS (Scheme 2.64). 

If we wish to direct the attack of halogen to the alkyl portion of an alkene molecule, then, we choose conditions that are favorable for the free-radical reaction and unfavorable for the ionic reaction. Chemists of the Shell Development Company found that, at a temperature of 500-600°, a mixture of gaseous propylene and chlorine yields chiefly the substitution product, 3-chloro-l-propene, known as allyl chloride (CH2=CH—CH2— = allyl). Bromine behaves similarly. 

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