Radical Addition to Alkenes (HBr/Peroxides)

Throughout the 1920s and 1930s, organic chemists encountered a persistent and deeply frustrating puzzle: the addition of HBr to unsymmetrical alkenes sometimes yielded the product predicted by Markovnikov's rule, and other times yielded the opposite regiochemistry. Laboratories that used freshly purified reagents consistently obtained Markovnikov products, while those using older or impure reagents frequently reported anti-Markovnikov addition. The irreproducibility was so severe that it became known as the peroxide effect, once Morris Kharasch and Frank Mayo demonstrated that trace organic peroxides—formed by autoxidation of ethers used as solvents—were the culprit. Their work established that radical intermediates, rather than carbocations, governed the regiochemistry under these conditions.

The central question that emerged from this historical episode remains essential today: why does the presence of peroxides reverse the regiochemistry of HBr addition, and why is this reversal unique to HBr among the hydrogen halides? Answering this requires a thorough understanding of radical chain mechanisms, the thermodynamics of individual propagation steps, and the kinetic factors that govern radical selectivity.

Radical addition to alkenes differs fundamentally from ionic addition in both the nature of the reactive intermediates and the regiochemical outcome. In ionic (electrophilic) addition, a proton adds first to generate the more stable carbocation, which then captures the nucleophilic halide—producing the Markovnikov product. In radical addition initiated by peroxides, a bromine radical adds first to generate the more stable carbon radical, and hydrogen is subsequently transferred from HBr—yielding the anti-Markovnikov product. The entire process operates through a radical chain mechanism consisting of three phases: initiation, propagation, and termination.

Examining the diagram closely, note that in propagation step 1, Br· adds to the terminal (less substituted) carbon of propene, generating a secondary carbon radical on C-2. This regioselectivity is thermodynamically driven: a secondary radical is approximately 12 kJ/mol more stable than the corresponding primary radical, and the transition state for radical addition reflects this stability difference. In propagation step 2, the carbon radical abstracts hydrogen from HBr (the weakest H–X bond among the hydrogen halides, at ~366 kJ/mol), regenerating the Br· chain carrier. The self-sustaining nature of this cycle means that a single initiation event can produce thousands of product molecules before termination intervenes, reflecting the high kinetic chain length of this process.

Understanding why the radical chain is self-sustaining—and why only HBr participates—requires a quantitative analysis of the enthalpy changes in each propagation step. We use bond dissociation energies (BDEs) to compute ΔH° for each elementary step. Recall that ΔH°_rxn = Σ(BDEs of bonds broken) − Σ(BDEs of bonds formed). For a radical chain to be viable, both propagation steps must be exothermic or at least thermoneutral.

Why Not HCl or HI?

The table reveals that HBr occupies a unique thermodynamic window. The H–Cl bond is too strong: although Cl· adds exothermically to the alkene, the subsequent H-abstraction from HCl by the carbon radical is endothermic because the H–Cl BDE (431 kJ/mol) exceeds the C–H BDE being formed (~410 kJ/mol). Conversely, the H–I bond is too weak: I· lacks the energetic driving force to add to the alkene in the first place because the C–I bond formed (~222 kJ/mol) does not compensate for breaking the π bond (~268 kJ/mol). Only for HBr are both propagation steps thermodynamically downhill, allowing the chain to proceed efficiently.

The most consequential feature of radical addition is its reversed regiochemistry relative to ionic electrophilic addition. In the absence of peroxides, HBr undergoes electrophilic addition: the proton adds to the less substituted carbon (following Markovnikov's rule) to generate the more stable carbocation at the more substituted position. In the presence of peroxides, Br· adds to the less substituted carbon for a different but analogous reason—the resulting carbon radical at the more substituted position is more stable. The outcome is that Br ends up on opposite carbons in the two pathways.

A subtle but critical point emerges from this comparison: the guiding principle in both pathways is identical—the more stable intermediate is preferred. In ionic addition, H⁺ adds first (forming the more substituted carbocation), so Br ends up on the more substituted carbon. In radical addition, Br· adds first (forming the more substituted radical), so Br ends up on the less substituted carbon. The reversal in regiochemistry arises not from a reversal in selectivity principles but from a reversal in which atom adds first.

Consider the reaction of 1-methylcyclohexene with HBr in the presence of di-tert-butyl peroxide (DTBP). Predict the major product and draw the complete radical mechanism.

A practicing organic chemist must choose between ionic and radical conditions depending on the desired regiochemical outcome. Each pathway has distinct advantages and constraints that influence synthetic strategy.

The anti-Markovnikov addition of HBr to alkenes is the gateway reaction in a much broader landscape of radical-mediated transformations. In Organic Chemistry 2 and beyond, you will encounter increasingly powerful radical methods—from atom transfer radical polymerization (ATRP) to radical cyclizations (e.g., Baldwin's rules applied to radical ring closure), and modern photoredox catalysis that generates radicals under mild, visible-light conditions. The mechanistic reasoning you develop here—evaluating BDEs, assessing radical stability, and thinking about chain kinetics—transfers directly to these advanced contexts.

One area of particular modern significance is thiol–ene chemistry, which is mechanistically almost identical to HBr radical addition: a thiyl radical (RS·) adds to an alkene to form a carbon radical, which then abstracts hydrogen from RSH to regenerate the chain carrier. This reaction, sometimes called a "radical click" reaction, is widely used in materials science, bioconjugation, and polymer cross-linking. The principles of regioselectivity and chain kinetics that you learn in the context of HBr/peroxides apply directly.