Understanding the Markovnikov Rule

Vadim Markovnikov Understanding the Markovnikov RuleSlaying the Markovnikov Rule to Its Long-Deserved Resting Place

When it comes to studying the reactivity of alkenes and alkynes with various reagents, nothing leads to more confusion than the Markovnikov Rule. Proposed in 1870 to explain a limited finite set of results, the rule persists in Organic Chemistry texts to this day. The source of confusion is not the logic of the rule, but rather the rule itself, as it is used in austerely limited form by most undergraduates to memorize the outcome of electrophilic addition reactions to alkenes and alkynes.

Alkenes and alkynes undergo electrophilic addition chemistry with reagents such as hydrogen bromide, hydronium ion and mercuric acetate to form what has been commonly accepted as the “Markovnikov product,” wherein the course of the reaction is said to follow the Markovnikov Rule. There are several definitions of the Markovnikov Rule “polluting” undergraduate Organic Chemistry textbooks. One such version says that, “the least substituted carbon gets the hydrogen.” What happens when the electrophile isn’t a Bronsted-Lowry acid? Another version claims “the most substituted carbon gets the halogen.” What happens when the reaction is run under radical conditions or using a reagent not favoring these results?

When the Markovnikov Rule is introduced in Organic Chemistry, students struggle to remember when the rule applies, and when it doesn’t. They memorize their way through this “dilemma,” hoping their memory doesn’t fail them during an exam.

So where did the Markovnikov Rule come from, and why is it still in the textbooks? In 1870, Russian chemist Vladimir Markovnikov conducted a series of experiments on alkenes, including monosubstituted, disubstituted, and trisubstituted alkenes. His experiments exclusively utilized hydrogen halide based Bronsted-Lowry acids. Most experiments, when run in the absence of peroxides, proceeded in a very predictable manner. The alkene (Lewis base) reacted with an acidic proton source leading to formation of the most stable carbocation, either directly or via hydride or alkyl shift. Having no cognizance of such rearrangements at the time (they were first proven by American chemist Frank Whitmore 1932), Markovnikov postulated a rule that communicated his results to the scientific world for the sake of reproducibility.

It’s important to note this rule doesn’t take into account the change in reaction mechanism due to peroxides, nor does it take into account Lewis acids not bearing acidic protons. Hence, the Markovnikov Rule is extremely limited in application.

Later, chemists experimenting with the same alkenes and hydrogen halides as Markovnikov, realized that the presence of peroxides in the reaction medium led to a regiochemical anomaly… an “anti-Markovnikov” product. This term became etched into the chemical literature due to a lack of understanding of the radical (single electron transfer) reaction mechanism taken by hydrogen halides in the presence of peroxides. If one were to react 2-methylbut-2-ene 1 with anhydrous HBr (Scheme I) in the presence of di-tert-butyl peroxide, 2-bromo-3-methylbutane 5 would make up the majority of the product mixture. The result “appears” to be anti-Markovnikov if one’s expectations involve a carbocation mechanism.

Markovnikov Rule Understanding the Markovnikov Rule

Bromine radical adds to 2-methylbut-2-ene 1 (Scheme II) to generate the 2-bromo-3-methylbut-3-yl radical 4, which so happens to be the most stable radical under the circumstances. The reaction is completed when the alkyl radical 4 abstracts a hydrogen atom from hydrogen bromide (a propagation step in the chain reaction) thereby affording the observed product.

For the sake of simplicity, if we exclude hydride and alkyl shifts from the conversation, the results are quite easily explained. Hydrogen halides add to alkene 1, forming the 2-methylbut-2-yl cation 2. In the presence of peroxides, the same hydrogen halides add to alkene 1, forming the 2-halo-3-methylbut-3-yl radical 4. In both circumstances “something” added to 1, forming the most stable intermediate with the cation or radical localized on the 3° carbon.

Markovnikov Rule 2 Understanding the Markovnikov RuleKeep in mind, radical stability parallels carbocation stability exactly: 3° > 2° > 1° > CH3.

Tertiary carbocations are stabilized via hyperconjugation with CH σ bonding orbitals (σCH to p donation) on neighboring alkyl groups. Likewise, tertiary radicals are stabilized in a comparable manner. Albeit hyperconjugation has roots in quantum mechanics, think of it as a through space donation of electron density resulting in stabilization of an adjacent electron deficient carbon.

Taking this notion into consideration, we’re ready for a new version (not in the textbooks yet) of the Markovnikov Rule, the “Markovnikov Prime Rule,”

Stuff adds to alkenes and alkynes to form the most stable intermediate.

It’s that simple. Let’s test this on the well know hydroboration-oxidation reaction. Borane is a compound containing boron attached to three hydrogens. The electronegativity of boron on the Pauling scale is 2.0, and the electronegativity of hydrogen is 2.1, meaning hydrogen is the negative end of the dipole in the B-H bond, and hence behaves more like a hydride anion than a proton. Therefore, boron is the electrophilic center in this reagent.

Borane adds to 2-methylbut-2-ene (Scheme III), forming (3-methylbutan-2-yl)borane 7 as an intermediate, which proceeds to react with two more alkene moieties, generating tris(3-methylbutan-2-yl)borane 8 as a downstream intermediate. Oxidative workup with sodium hydroxide and hydrogen peroxide extrudes boron with retention of configuration about carbon, affording three equivalents of 3-methylbutan-2-ol 9.

Markovnikov Rule 3 Understanding the Markovnikov RuleWas the Markovnikov Prime Rule ever violated? No. The electrophilic boron added to the correct carbon resulting in buildup of a partial positive charge in the 2-position during the transition state of the concerted reaction. If we simplify the Markovnikov Rule to be more inclusive of reaction mechanisms outside dipolar electrophilic addition (including hydride and alkyl shifts), then we realize the rule is never violated.

Please take time to understand the underlying principles of this short article so you don’t have to rely upon memory ever again to determine the regiochemistry of a reaction involving “stuff” and an alkene or alkyne.

© 2012 O-Chem Prof

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2 thoughts on “Understanding the Markovnikov Rule

  1. Resp. sir,
    In diboration reaction the addition of water molecule to the alkene takes place contrary to Markonikov’s rule. I.e. the negatively charged group gets attached to the carbon carrying more no of H atoms. According to the rule it should get attached ti the other carbon atom which carries lesser no. of H atoms. This happens because the carbon atom to which H gets attached is attached to two methyl groups whuch show posive inductive effect .

    • Dr. Moharil,

      Thank you for your kind comment.

      If one were to envision water as having added to alkene (1), then the product (9) would appear to be anti-Markovnikov.

      Borane adds to alkene (1) with the electrophilic boron attaching to place a partial positive charge on the carbon best able to support such a charge, and hence the addition of borane to alkene (1) proceeds in a Markovnikov manner. The H2O2/NaOH workup produces HOO- anion in quantity, a Lewis base, which adds to the empty p-orbital on boron, forming a Lewis acid-base adduct.

      This adduct undergoes rearrangement with retention of configuration about the chiral carbon-based center. The final step is a “net substitution” on carbon (actually a nucleophilic attack of the carbon-boron bond on the electrophilic oxygen in the R-B-O-OH system), via rearrangement with retention of configuration, leading to a boronate ester ultimately cleaved by aqueous hydroxide.

      The rate determining step leading to the formation of intermediate (7) proceeded in a Markovnikov manner, and hence the reaction never violated Markovnikov’s Rule.

      I agree, the hyperconjugative effect of the dimethyl functionality stabilizes the partial positive charge in transition state (6) leading to regiospecificity in the reaction.

      Kindest Regards,
      O-Chem Prof

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