Peroxides, anti-Markovnikov addition

The addition of hydrogen halides to simple alkenes, in the absence of peroxides, takes place by an electrophilic mechanism, and the orientation is in accord with Markovnikov s rule. " When peroxides are added, the addition of HBr occurs by a free-radical mechanism and the orientation is anti-Markovnikov (p. 985). It must be emphasized that this is true only for HBr. Free-radical addition of HF and HI has never been observed, even in the presence of peroxides, and of HCl only rarely. In the rare cases where free-radieal addition of HCl was noted, the orientation was still Markovnikov, presumably beeause the more stable product was formed. Free-radical addition of HF, HI, and HCl is energetically unfavorable (see the discussions on pp. 900, 910). It has often been found that anti-Markovnikov addition of HBr takes place even when peroxides have not been added. This happens because the substrate alkenes absorb oxygen from the air, forming small amounts of peroxides... 

When you do the same reaction (as above) in the presence of peroxides (R-O-O-R), you get an anti-Markovnikov addition of HBr across the double bond. Draw the product of an anti-Markovnikov addition. 

Answer In order to determine whether or not to use peroxides, we must decide whether the desired transformation represents a Markovnikov addition or an anti-Markovnikov addition. When we compare the starting alkene above with the desired product, we see that we need to place the Br at the more substituted carbon (i.e., Markovnikov addition). Therefore, we need an ionic pathway to predominate, and we should not use peroxides. We just use HBr ... 

Take special notice of what we can accomplish when we use this technique it gives us the power to move the position of a double bond. When using this technique, we must carefully consider the regiochemistry of each step. In the first step (addition), we must decide whether we want a Markovnikov addition (HBr), or an anti-Markovnikov addition (HBr with peroxides). Also, in the second step (elimination), we must decide whether we want to form the Zaitsev product or the Hofmann product (which we can control by carefully choosing our base, ethoxide or fcrf-butoxide). Get some practice with this technique in the following problems. 

The addition of hydrogen halide to alkene is another classical electrophilic addition of alkene. Although normally such reactions are carried out under anhydrous conditions, occasionally aqueous conditions have been used.25 However, some difference in regioselectivity (Markovnikov and anti-Markovnikov addition) was observed. The addition product formed in an organic solvent with dry HBr gives exclusively the 1-Br derivative whereas with aq. HBr, 2-Br derivative is formed. The difference in the products formed by the two methods is believed to be due primarily to the difference in the solvents and not to the presence of any peroxide in the olefin.26... 

This anti-Markovnikov addition occurs only when HBr is used in the presence of peroxides and does not occur significantly with HF, HC1, and HI even when peroxides are present. 

Anti-Markovnikov addition of HBr to alkynes occur when peroxides are present. 1) These reactions take place through a free radical mechanism. 

Kharasch and Mayo in 1933," in the first of many papers on the subject, showed that the addition of HBr to allyl bromide in the presence of light and air occurs rapidly to yield 1,3-dibromopropane, whereas in the absence of air and with purified reagents, the reaction is slow and 1,2-dibromopropane is formed. The latter reaction is the normal addition occurring by an ionic pathway giving the Markovnikov orientation. In 1933 the mechanism of the abnormal process ( anti-Markovnikov addition) was not discussed, and it was only in 1937 that the free radical chain mechanism for this process was proposed by Kharasch and his co-workers. "" The mechanism was extended to propene, for which the role of peroxides in promoting the reaction was demonstrated (equations 30, 31). This mechanism was also proposed... 

Hydroboration-oxidation of alkenes preparation of alcohols Addition of water to alkenes by hydroboration-oxidation gives alcohols via anti-Markovnikov addition. This addition is opposite to the acid-catalysed addition of water. Hydrohoration is regioselective and syn stereospecific. In the addition reaction, borane bonds to the less substituted carbon, and hydrogen to the more substituted carbon of the double bond. For example, propene reacts with borane and THF complex, followed by oxidation with basic hydrogen peroxide (H2O2), to yield propanol. 

Hydroboration-oxidation of alkynes preparation of aldehydes and ketones Hydroboration-oxidation of terminal alkynes gives syn addition of water across the triple bond. The reaction is regioselective and follows anti-Markovnikov addition. Terminal alkynes are converted to aldehydes, and all other alkynes are converted to ketones. A sterically hindered dialkylborane must be used to prevent the addition of two borane molecules. A vinyl borane is produced with anU-Markovnikov orientation, which is oxidized by basic hydrogen peroxide to an enol. This enol tautomerizes readily to the more stable keto form. 

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. 

Tho reaction follows Markovnikov s rule because the rule dictates the formation of the more stable carbocation. You should be aware that if peroxides (ROOR) are present the bromine, not the hydrogen, will add to the least substituted carbon. This is called an anti-Markovnikov addition. The other halogens will still follow Markovnikov s rule even in the presence of peroxides. 

C is correct. Anti-Markovnikov alkene free radical addition is demonstrated by reaction mechanisms 1 and 2, both of which rely on peroxides as reagents. Based on tine experimental results provided by the question stem, anti-Markovnikov addition only succeeds using HBr. 

A well-known example of the application of mechanistic understanding to help to control product yields is also of commercial significance - the addition of HBr to alkenes which may occur via cationic or radical mechanisms, Scheme 2.1 [2a]. Very pure alk-l-enes (1), in the absence of peroxides, react to give the 2-bromo-products (2) by Markovnikov addition. In the presence of peroxides or other radical sources, anti-Markovnikov addition gives the 1-bromo-products (3). 

Hexyne has the triple bond in the middle of a carbon chain and is termed an internal alkyne. If, instead, an alkyne with the triple bond at the end of the carbon chain, a 1-alkyne or a terminal alkyne, were used in this reaction, then the reaction might be useful for the synthesis of aldehydes. The boron is expected to add to the terminal carbon of a 1-alkyne. Reaction with basic hydrogen peroxide would produce the enol resulting from anti-Markovnikov addition of water to the alkyne. Tautomerization of this enol would produce an aldehyde. Unfortunately, the vinylborane produced from a 1-alkyne reacts with a second equivalent of boron as shown in the following reaction. The product, with two borons bonded to the end carbon, does not produce an aldehyde when treated with basic hydrogen peroxide. 

Oxidation of the vinylborane (using basic hydrogen peroxide) gives a vinyl alcohol (end), resulting from anti-Markovnikov addition of water across the triple bond. This end quickly tautomerizes to its more stable carbonyl (keto) form. In the case of a terminal alkyne, the keto product is an aldehyde. This sequence is an excellent method for converting terminal alkynes to aldehydes. 

Markovnikov s rnle The hydrogen of the acid attaches itself to the carbon atom which already has the greatest number of hydrogens. In the presence of peroxide, HBr will undergo anti-Markovnikov addition. 

To account for this peroxide effect, Kharasch and Mayo proposed that addition can take place by two entirely different mechanisms Markovnikov addition by the ionic mechanism that we have just discussed, and anti-Markovnikov addition by a free-radical mechanism. Peroxides initiate the free-radical reaction in their absence (or if an inhibitor, p. 189, is addedX addition follows the usual ionic path. 

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. 

The anti-Markovnikov addition of HBr to alkenes was probably the first free-radical addition reaction to be discovered. The discovery was inadvertent around the turn of the twentieth century, scientists studying the regiochemistry of addition of HBr to alkenes found that the proportion of Markovnikov to anti-Markovnikov addition products varied inexplicably from run to run. Eventually, it was discovered that impurities such as O2 and peroxides greatly increased the amount of anti-Markovnikov addition product. The results were later explained by a free-radical addition mechanism. The anti-Markovnikov regiochemistry derives from the addi-ton of the Br- radical to the less substituted C of the alkene (steric reasons) to give the lower energy, more substituted radical (electronic reasons). In a polar reaction, Br- would add to the more substituted C of the alkene. 

Hydroboration, followed by oxidation using alkaline hydrogen peroxide, results in overall anti-Markovnikov addition of water. 

Anti-Markovnikov additions occur in the presence of free-radical catalysts such as peroxides, azo... 

Reactions can be run to give the opposite of the expected product, yielding what is called anti-Markovnikov addition. That is, hydrogen ends up on the more substituted carbon of the double bond. The hydroboration/oxidation reaction yields this, as do reactions that are conducted in peroxides. 

Even conceptually simple reactions - such as the textbook anti-Markovnikov addition of HBr to isobutene, catalysed by dibenzoyl peroxide, can lead to sets of simultaneous equations which may need computer algebra such as Mathe-matica to solve. 

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. ... 

The reaction with HBr is also significant in terms of regiochemistry. The reaction results in the anti-Markovnikov orientation, with the bromine adding to the less-substituted carbon of the double bond. The anti-Markovnikov addition of HBr to alkenes was one of the earliest free radical reactions to be put on a firm mechanistic basis. In the presence of a suitable initiator, such as a peroxide, a radical chain mechanism becomes competitive with the ionic mechanism for addition of HBr. 

Scheme 11.5 gives some examples of these radical addition reactions. Entries 1 to 3 show anti-Markovnikov addition of HBr. The reaction in Entry 1 was carried out by passing HBr gas into the alkene, using benzoyl peroxide as the initiator, apparently near room temperature. Entry 2 is an example of anti-Markovnikov addition to... 

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. 

Two further examples—of which the first is admittedly disputed—may be cited to show that it is not only peroxides, azoisobutyronitrile, and similar additions that catalyse anti-Markovnikov addition of HBr to olefins. It has been shown157 that 1-bromopentane and 1-bromoheptane are formed exclusively when dry HBr is led at atmospheric pressure into a stirred solution of peroxide-free 1-pentene or 1-heptene, respectively, in CC14 or hexane at —10 to —12° or in glacial acetic acid at 0-5° (1.5-3 h) but if these olefins are shaken with 48% aqueous HBr for 2 months at room temperature in the dark, then the addition gives exclusively 2-bromopentane and 2-bromoheptane. Also, addition of HBr to propene without a solvent gives 2-bromopropane,158 but the reaction in n-pentane gives the anti-Markovnikov adduct 1-bromopropane even in absence of peroxides and air (dilution effect159). 

The dilution effect has been used in conjunction with addition of a peroxide to force anti-Markovnikov addition. 

An intermediate esterification is required to achieve anti-Markovnikov addition of HBr to higher unsaturated alcohols. For instance, even when a peroxide is added, 10-undecen-l-ol and HBr afford 10-bromo-l-undecanol, whereas HBr adds to 10-undecenyl acetate in the presence of peroxides so that the bromine appears in the 11-position whereas in the presence of antioxidants (H2 and diphenylamine) it appears in the 10-position.200 The HBr adducts obtained from the acetates in the presence of dibenzoyl peroxide can be converted into the bromo alcohols by transesterification with methanol and / -toluenesulfonic acid.201 11-Bromo-1-undecanol, 13-bromo-l-tridecanol, and 15-bromo-l-pentadecan ol can also be obtained by intermediate conversion of the corresponding co-unsaturated alcohols into the boric esters. 

The addition of HBr to 1-butene forms 2-bromobutane. But what if you wanted to synthesize 1-bromobutane The formation of 1-bromobutane requires the anti-Markovnikov addition of HBr. If an alkyl peroxide (ROOR) is added to the reaction mixture, the product of the addition reaction will be the desired 1-bromobutane. Thus, the presence of a peroxide causes the anti-Markovnikov addition of HBr. 

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