Anti-Markovnikov addition of hydrogen bromide

Redical Addition to Alkenes the Anti-Markovnikov Addition of Hydrogen Bromide... 

Reaction 1 has been postulated both in oxidations of alkanes in the vapor phase (29) and in the anti-Markovnikov addition of hydrogen bromide to olefins in the liquid phase (14). Reaction 2 involves the established mechanism for free-radical bromination of aromatic side chains (2). Reaction 4 as part of the propagation step, established in earlier work without bromine radicals (26), was not invoked by Ravens, because of the absence of [RCH3] in the rate equation. Equations 4 to 6, in which Reaction 6 was rate-determining, were replaced by Ravens by the reaction of peroxy radical with Co2+ ... 

The alkylating agent, 1-bromobutane, is prepared from 1-butene by free-radical (anti-Markovnikov) addition of hydrogen bromide. 

Anti-Markovnikov addition of hydrogen bromide to alkynes occurs when peroxides are present in the reaction mixture. These reactions take place through a free-radical mechanism (Section 10.10) ... 

RADICAL ADDITION TO ALKENES THE ANTI-MARKOVNIKOV ADDITION OF HYDROGEN BROMIDE... 

The mechanism for anti-Markovnikov addition of hydrogen bromide is a radical chain reaction initiated by peroxides. 

Electrophilic addition of hydrogen bromide to alkenes follows Markovnikov s rule, leading to the product with halogen on the more-substituted position. However, trace amounts of hydroperoxides (among other impurities ) may initiate a reaction that gives rise to the anti-Markovnikov product, with bromine in the less-substituted position. 

The change in regiochemistry is a result of a change in the mechanism of the reaction, from an ionic mechanism in the Markovnikov reaction to a radical chain mechanism in the anti-Markovnikov reaction. The radical chain mechanism for the addition of hydrogen bromide to 1-butene is outlined in the following equations ... 

This problem is even worse for alkenes more complex than ethylene. Equally simple reactions (in a formal sense ) such as the addition of hydrogen bromide or hypobromous acid are also far from being unambiguous and as a rule give rise to a mixture of isomers containing both the predominant Markovnikov (M) as well as anti-Markovnikov (aM) adducts. 

This polar mechanism is in contrast to the non-polar radical mechanism for the addition of hydrogen bromide that we will study in the next section. We will see that the radical mechanism gives rise to addition with the //7//-Markovnikov regiochemistry. There is a further difference between the polar and the non-polar reactions, in that the radical addition is usually syn in nature, assuming that the radical has a short half life, while, as we have seen, the polar reaction is usually anti in nature. 

The regioselectivity of addition of hydrogen bromide to alkenes can be complicated if a free-radical chain addition occurs in competition with the ionic addition. The free-radical chain reaction is readily initiated by peroxidic impurities or by light and leads to the anti Markovnikov addition product. The mechanism of this reaction is considered more fully in Chapter 11. Conditions that minimize the competing radical addition include use of high-purity alkene and solvent, exclusion of light, and addition of a radical inhibitor. ... 

Before 1933, the orientation of the addition of hydrogen bromide to alkenes was the subject of much confusion. At times addition occurred in accordance with Markovnikovs rule at other times it occurred in just the opposite manner. Many instances were reported where, under what seemed to be the same experimental conditions, Markovnikov additions were obtained in one laboratory and anti-Markovnikov additions in another. At times even the same chemist would obtain different results using the same conditions but on different occasions. 

Several of the procedures in this chapter involve addition reactions characteristic of alkenes. Two of them, the addition of hydrogen bromide to 1-hexene (Sec. 10.5) and of borane to a-pinene (Sec. 10.8), represent examples in which both the reagent and the alkene to which it is adding are unsymmetrical. Consequently, identifying the products from these reactions provides a means of testing whether a Markovnikov or an anti-Markovnikov mode of addition has occurred. 

FIGURE 11.25 Addition of hydrogen bromide to alkenes in the presence of peroxide is anti-Markovnikov. 

When alkenes containing peroxides or hydroperoxides react with hydrogen bromide, anti-Markovnikov addition of HBr occurs. 

The mechanism for the addition of hydrogen bromide to 1-phenylpropene in the presence of peroxides is a chain mechanism analogous to the one we discussed when we described anti-Markovnikov addition in Section 10.9. The step that determines the orientation of the reaction is the first chain-propagating step. Bromine attacks the second carbon atom of the chain because by doing so the reaction produces a more stable benzylic radical. Had the bromine atom attacked the double bond in the opposite way, a less stable secondary radical would have been formed. 

Exceptions to the Markovnikov rule when hydrogen bromide reacts with unsym-metric alkenes have long been known.117,118 The reaction for this anti-Markovnikov addition was explained as being a chain reaction with the involvement of bromine atoms influenced by the presence of peroxides.119-121 Both added peroxides and peroxides formed by the action of oxygen (air) on the alkene are effective. 

The mechanism involves addition of a bromine atom to the double bond. It is supported, therefore, by the fact that anti-Markovnikov addition is caused not only by the presence of peroxides but also by irradiation with light of a wavelength known to dissociate hydrogen bromide into hydrogen and bromine atoms. 

HBr reacts with an alkene to give the more substituted (and more stable) car-bocation intermediate, and the nucleophile is incorporated at that position (see Section 10.2). In experiments designed to further probe this reaction, hydrogen bromide (HBr) is added to undec-lO-enoic acid (153) in a hydrocarbon solvent, but benzoyl peroxide (149) is added to the reaction. When the product is isolated, 11-bromoundecanoic acid (154) is obtained in 70% yield. The bromine is attached to the less substituted carbon. Because Markovnikov s rule places the hydrogen atom on the less substituted carbon atom of the C=C unit and the bromine on the more substituted, formation of 154 is exactly the opposite result—an anti-Markovnikov addition. 

When freshly distilled 1-butene is exposed to hydrogen bromide, clean Markovnikov addition to give 2-bromobutane is observed. This result is in accord with the ionic mechanism for electrophilic addition of HBr discussed in Section 12-3. Curiously, the same reaction, when carried out with a sample of 1-butene that has been exposed to air, proceeds much more quickly and gives an entirely different result. In this case, we isolate 1-bromobutane, formed by anti-Markovnikov addition. 

The stereochemistry of this type of addition is typically anti, particularly when excess halide ion is used. A second molecule of hydrogen bromide may also add, with regioselec-tivity that follows Markovnikov s rule, giving the product with both bromine atoms bound to the same carbon, a geminal dihaloalkane. 

The rate of addition depends on the concentration of both the butylene and the reagent HZ. The addition requires an acidic reagent and the orientation of the addition is regioselective (Markovnikov). The relative reactivities of the isomers are related to the relative stabiUty of the intermediate carbocation and are isobutylene 1 — butene > 2 — butenes. Addition to the 1-butene is less hindered than to the 2-butenes. For hydrogen bromide addition, the preferred orientation of the addition can be altered from Markovnikov to anti-Markovnikov by the presence of peroxides involving a free-radical mechanism. 

Now, just the same sort of rationalization can be applied to the radical addition, in that the more favourable secondary radical is predominantly produced. This, in turn, leads to addition of HBr in what is the anti-Markovnikov orientation. The apparent difference is because the electrophile in the ionic mechanism is a proton, and bromide then quenches the resultant cation. In the radical reaction, the attacking species is a bromine atom, and a hydrogen atom is then used to quench the radical. This is effectively a reverse sequence for the addition process but, nevertheless, the stability of the intermediate carbocation or radical is the defining feature. The terminologies Markovnikov or anti-Markovnikov orientation may be confusing and difficult to remember consider the mechanism and it all makes sense. 

In the presence of a radical initiator, alkenes react with reactive molecules such as hydrogen bromide to give simple 1 1 adducts rather than a polymer. The initiator radical reacts rapidly with an HBr molecule to give a bromine atom (6.49), which starts the chain reaction. In the first propagation step, the bromine atom adds to the alkene 61 to give the adduct radical 62 (reaction 6.50). Since 62 abstracts a hydrogen atom from HBr by reaction (6.51) more rapidly than it would add to the alkene to form a polymer radical as in (6.43), the chain continues with reactions (6.50) and (6.51) as the propagating steps, and the product is the primary bromo compound 63. This anti-Markovniko addition is in the reverse direction to the polar addition discussed in Chapter 5. Since the radical chain reaction is faster than the polar reaction, the anti-Markovnikov product dominates if radicals are present. If the Markovnikov product is required, the reaction must be carried out in the dark, in the absence of free radical initiators, and preferably with a radical inhibitor present. 

---