Name: peroxide effect in hbr alkene addition
Uploaded: 2023-04-30T18:28:36.000Z
Duration: 2 min 35 s
Channel: JoVE

While hydrogen bromide typically adds to an unsymmetrical alkene like 2-methylpropene to form the Markovnikov product, in the presence of peroxide, the alternate regioisomer &#8212; the less-substituted alkyl halide &#8212; is obtained.
Anti-Markovnikov regioselectivity, called the peroxide effect, is attributed to a free-radical reaction mechanism in the presence of peroxide.
In the first initiation step, the weak oxygen&#8211;oxygen bond in peroxide breaks homolytically, as indicated by a fishhook arrow, in the presence of heat or light to form alkoxy radicals. The second initiation step is abstraction of hydrogen from hydrogen bromide by an alkoxy radical, releasing the bromine radical.
The selective abstraction of hydrogen over bromine by the alkoxy radical is explained by the relative enthalpies of the oxygen&#8211;hydrogen and oxygen&#8211;bromine bond formation reactions.
The propagation sequence is marked by the addition of a bromine radical to the less-branched carbon of the alkene, producing a more-substituted alkyl radical. The chain reaction is set up as the alkyl radical abstracts hydrogen, again forming a bromine radical. For each radical consumed in the propagation step, another is produced.
As the reactants are depleted, radicals combine with each other, terminating the chain reaction.
The formation of the anti-Markovnikov product in the presence of peroxide is partially due to less steric hindrance being posed to the incoming bromine radical by the less-branched end of the alkene, producing a lower-energy transition state.
Another reason is the formation of a more stable alkyl radical when bromine reacts at the less-substituted carbon as tertiary free radicals are more stable than primary ones.
Interestingly, the peroxide effect is not observed with hydrogen iodide and hydrogen chloride, as the propagation steps of addition of the iodine radical to the alkene and the reaction of the alkyl radical with hydrogen chloride are thermodynamically unfavorable.
During the addition of hydrogen bromide to an alkene, the bromine radical can approach from either face of the alkene. Hence, when a new chiral center is generated, a racemic mixture of the product is obtained.

regioselectivity of electrophilic additions-peroxide effect

Regioselectivity of Electrophilic Additions-Peroxide Effect

In the presence of organic peroxides, the addition of hydrogen bromide to an alkene yields the isomer that is not predicted by Markovnikov&#8217;s rule. For example, the addition of hydrogen bromide to 2-methylpropene in the presence of peroxides gives 1-bromo-2-methylpropane. This addition reaction proceeds via a free radical mechanism, which reverses the regioselectivity. The free radical reaction mechanism involves three stages: initiation, propagation, and termination.
<img alt="Hydroboration oxidation, alkene to alcohol, reaction mechanism, chemical equation diagram." src="/files/ftp_upload/11772/11772_PT_Figure_1.svg" style="text-align: center; height: 75px;" data-altupdatedat="1761830439000" data-alt="Figure1" />
In the first initiation step, an oxygen&#8211;oxygen bond in the radical initiator undergoes homolytic cleavage.
<img alt="Chemical reaction diagram; thermal or photochemical bond cleavage; peroxy radical formation." src="/files/ftp_upload/11772/11772_PT_Figure_2.svg" style="text-align: center; height: 65px;" data-altupdatedat="1761830439000" data-alt="Figure2" />
The di-tert-butyl peroxide is an excellent free-radical initiator as the homolysis of the O&#8211;O bond requires just 159 kJ mol&#8211;1 (38 kcal mol&#8211;1) of energy.
<img alt="Radical halogenation reaction, chemical equation diagram, illustrating C-H bond formation." src="/files/ftp_upload/11772/11772_PT_Figure_3.svg" style="text-align: center; height: 45px;" data-altupdatedat="1761830439000" data-alt="Figure3" />
The second initiation step involves the exothermic (&#916;H = &#8211;70 kJ mol&#8211;1) abstraction of hydrogen from HBr by the tert-butoxy radical. The abstraction of bromine, however, is thermodynamically unfavorable (&#916;H = 163 kJ mol&#8211;1).
In propagation steps, a bromine radical reacts with an alkene to generate an alkyl radical. 
<img alt="Free radical bromination mechanism, showing alkene reaction with Br radical, chemical diagram." src="/files/ftp_upload/11772/11772_PT_Figure_4.svg" style="text-align: center; height: 75px;" data-altupdatedat="1761830439000" data-alt="Figure4" />
The regioselective addition of bromine at the less substituted carbon in the presence of peroxide can be understood from the transition states. The transition state shows that the formation of the more substituted radical involves an attack by a bromine radical at the less substituted (and less hindered) carbon atom, which is lower in energy than the transition state for the less substituted radical. Another reason is the stability exhibited by the more substituted radicals owing to the hyperconjugation and inductive effect.
<img alt="Radical stability hierarchy; 3&#176; &#62; 2&#176; &#62; 1&#176;; chemical stability diagram; organic chemistry concept." src="/files/ftp_upload/11772/11772_PT_Figure_5.svg" style="text-align: center; height: 75px;" data-altupdatedat="1761830439000" data-alt="Figure5" />
<img alt="Radical alkyl bromide formation, arrow notation, molecular structure, organic chemistry reaction diagram." src="/files/ftp_upload/11772/11772_PT_Figure_6.svg" style="text-align: center; height: 75px;" data-altupdatedat="1761830439000" data-alt="Figure6" />
The reaction is terminated when radicals combine to yield non-radical products.
<img alt="Organic reaction mechanism diagram, alkene bromination, showing reaction intermediates and product." src="/files/ftp_upload/11772/11772_PT_Figure_7.svg" style="text-align: center; height: 100px;" data-altupdatedat="1761830439000" data-alt="Figure7" />
<img alt="Bromine radical reaction mechanism; Br&#8226; + &#8226;Br forms Br2; chemical reaction diagram." src="/files/ftp_upload/11772/11772_PT_Figure_8.svg" style="text-align: center; height: 50px;" data-altupdatedat="1761830439000" data-alt="Figure8" />
While the peroxide-mediated addition of HI to an alkene does not occur because the first propagation step is endothermic, the reaction with HCl does not proceed as the second propagation step is endothermic.
In the addition of hydrogen bromide to an alkene, the bromine radicals can attack the less substituted vinylic carbon from either face to an equal extent. Hence, when an alkene is stereogenic, a racemic mixture of products is obtained. 
<img alt="Chiral molecule with bromine, structural formula, stereochemistry diagram, organic chemistry." src="/files/ftp_upload/11772/11772_PT_Figure_9.svg" style="text-align: center; height: 75px;" data-altupdatedat="1761830439000" data-alt="Figure9" />
<img alt="Organic chemistry diagram, bromobutane structural formula, showing molecular bonding and configuration." src="/files/ftp_upload/11772/11772_PT_Figure_10.svg" style="text-align: center; height: 75px;" data-altupdatedat="1761830439000" data-alt="Figure10" />

In the presence of organic peroxides, the addition of hydrogen bromide to an alkene yields the isomer that is not predicted by Markovnikov&#8217;s rule. ...

regioselectivity-of-electrophilic-additions-peroxide-effect

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Organic Chemistry

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Reactions of Alkenes

KEY TERMS AND CONCEPTS

peroxide effect in hbr alkene addition

Hydrogen bromide can add to an alkene in a way that goes against Markovnikov’s rule when organic peroxides are present. For example, 2-methylpropene reacts with HBr and peroxide to give 1-bromo-2-methylpropane. This change in product comes from a free radical mechanism, which reverses the usual regioselectivity.

The reaction has three stages: initiation, propagation, and termination. In initiation, an oxygen-oxygen bond in the radical initiator breaks by homolytic cleavage, meaning each atom keeps one electron. Di-tert-butyl peroxide is a good initiator because breaking its O-O bond needs only 159 kJ mol-1, or 38 kcal mol-1, of energy. A second initiation step follows when the tert-butoxy radical removes hydrogen from HBr. That step is exothermic, with ΔH = -70 kJ mol-1.

The radical does not abstract bromine from HBr because that step is thermodynamically unfavorable. Its ΔH is 163 kJ mol-1. In propagation, a bromine radical adds to the alkene and forms an alkyl radical. The bromine ends up on the less substituted carbon because that pathway has the lower-energy transition state. The attack also occurs at the less hindered carbon, and the resulting more substituted radical is more stable because of hyperconjugation and the inductive effect.

The reaction ends in termination when radicals combine to form non-radical products. The peroxide effect is not seen with HI because the first propagation step is endothermic. It also does not proceed with HCl because the second propagation step is endothermic. When a stereogenic alkene is involved, bromine radical attack can occur from either face equally, so the product is a racemic mixture.

Peroxide Effect in HBr Alkene Addition

Hydrogen bromide can add to an alkene in a way that goes against Markovnikov’s rule when organic peroxides are present. For example, 2-methylpropene reacts with HBr and peroxide to give 1-bromo-2-methylpropane. This change in product comes from a free radical mechanism, which reverses the usual regioselectivity. The reaction has three stages: initiation, propagation, and termination. In initiation, an oxygen-oxygen bond in the radical initiator breaks by homolytic cleavage, meaning each atom...

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Anti-Markovnikov Alcohols from Alkenes

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key terms and concepts

Learn how peroxide changes HBr addition to alkenes, reverses Markovnikov orientation, and proceeds by a free radical chain mechanism with racemic products.

Peroxide Effect in HBr Alkene Addition | JoVE K12

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Peroxide Effect in HBr Alkene Addition

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