Premed · Premed · Organic Chemistry 1
Lecture 16: Radical Reactions
Organic Chemistry I
Learning Objectives
By the end of this lecture, students will be able to:
- Define radicals and explain their electronic structure
- Describe radical stability trends and the factors that stabilize radicals
- Explain the three phases of radical chain reactions: initiation, propagation, termination
- Describe the mechanism of radical halogenation of alkanes
- Predict the products of radical chlorination and bromination considering selectivity
- Explain anti-Markovnikov addition of HBr to alkenes (radical mechanism)
- Describe radical polymerization
- Calculate product distributions using reactivity and statistical factors
Lecture Content
I. Introduction to Radicals
A radical (or free radical) is a species containing an unpaired electron. Radicals are neutral, highly reactive intermediates formed by homolytic bond cleavage, in which a bond breaks so that each atom retains one electron (A-B yielding A. + B.). This contrasts with heterolytic cleavage, where both electrons go to one atom. The unpaired electron is represented by a single dot in structural formulas.
A radical carbon is typically sp2 hybridized with trigonal planar geometry, and the unpaired electron resides in the unhybridized p orbital. This geometry resembles that of a carbocation, except that the p orbital contains one electron rather than being empty. Radicals are fundamentally different from carbocations (which bear a positive charge and an empty p orbital) and carbanions (which bear a negative charge and a filled orbital). Unlike ionic chemistry, radical reactions do not involve nucleophiles or electrophiles; instead, radicals react by abstracting atoms from other molecules or by combining with other radicals.
II. Radical Stability
Radical stability follows the same trend as carbocation stability: tertiary > secondary > primary > methyl. More substituted radicals are more stable because hyperconjugation allows adjacent C-H and C-C sigma bonds to donate electron density into the half-filled p orbital. More alkyl substituents provide more opportunities for hyperconjugation.
Allylic and benzylic radicals are especially stable because the unpaired electron is delocalized by resonance with an adjacent pi bond or aromatic ring. Bond dissociation energy (BDE), the energy required for homolytic cleavage of a bond, provides a quantitative measure of radical stability. A weaker C-H bond produces a more stable radical upon cleavage. Tertiary C-H BDE is approximately 397 kJ/mol, secondary approximately 410, primary approximately 420, and methyl approximately 439, while allylic and benzylic C-H bonds are even weaker at approximately 370 kJ/mol.
III. Radical Chain Reactions: General Framework
Most radical reactions proceed through a chain mechanism consisting of three phases. Initiation generates radicals from non-radical precursors, requiring an energy input from heat or UV light to achieve homolytic cleavage of a weak bond. Examples include the splitting of Cl2 or Br2 into halogen atoms, or the decomposition of a peroxide (ROOR) into alkoxy radicals. Only a small, catalytic amount of initiator is needed.
Propagation consists of the productive steps that form the desired product and regenerate a radical to continue the chain. Each propagation step consumes one radical and produces one radical, and the sum of all propagation steps gives the overall balanced equation. The chain continues as long as propagation steps repeat.
Termination occurs when two radicals combine to form a non-radical product, destroying chain carriers. Examples include the coupling of two chlorine atoms, a carbon radical with a chlorine atom, or two carbon radicals. Because radicals are present at very low concentrations, these bimolecular termination events are statistically rare but eventually halt every chain.
<image>Panel A: The three phases of a radical chain reaction illustrated for the chlorination of methane. Initiation: Cl-Cl bond breaks homolytically with UV light, producing 2 Cl radicals (shown with fishhook arrows). Propagation Step 1: Cl radical abstracts H from CH4, forming HCl and CH3 radical (fishhook arrows shown). Propagation Step 2: CH3 radical reacts with Cl2, forming CH3Cl and regenerating Cl radical. Termination: examples of Cl+Cl, CH3+Cl, and CH3+CH3 combinations. Panel B: An energy diagram for the propagation steps, showing the exothermic nature of the overall reaction with the individual barriers for each propagation step.</image>
IV. Radical Halogenation of Alkanes
The overall reaction for radical halogenation is R-H + X2 yielding R-X + HX, initiated by heat or UV light. Chlorination and bromination differ dramatically in their selectivity.
Chlorination is highly exothermic (delta H approximately -105 kJ/mol for methane) and shows low selectivity. The chlorine radical is so reactive that it abstracts hydrogen from all types of C-H bonds with relatively similar rates. The product distribution is therefore largely governed by statistical factors (the number of each type of hydrogen), modulated by modest reactivity differences with ratios of approximately 5.0 : 3.8 : 1.0 for tertiary : secondary : primary C-H bonds. A practical problem with chlorination is over-halogenation, as the product can react further.
Bromination is less exothermic (delta H approximately -30 kJ/mol for methane) and is highly selective. The bromine radical is less reactive and far more discriminating, preferentially abstracting the weakest C-H bond to form the most stable radical. The reactivity ratios are approximately 1600 : 82 : 1.0 for tertiary : secondary : primary, meaning bromination almost exclusively produces the tertiary product when one is available. This enormous selectivity difference is explained by Hammond's postulate: the more exothermic chlorination has an earlier, less selective transition state, while the more endothermic hydrogen abstraction step in bromination has a later transition state that more closely resembles the product radical.
V. Selectivity and Product Prediction
Predicting the product distribution of radical halogenation requires combining statistical and reactivity factors. The percentage of each product equals (number of hydrogens of that type multiplied by relative reactivity) divided by the sum for all types, multiplied by 100%.
Bromination of 2-methylbutane illustrates this calculation. The molecule has 9 primary hydrogens (on three CH3 groups), 2 secondary hydrogens, and 1 tertiary hydrogen. Multiplying each count by the relative reactivity gives 9 x 1 = 9 for primary, 2 x 82 = 164 for secondary, and 1 x 1600 = 1600 for tertiary, with a total of 1773. The tertiary bromide constitutes 90.2% of the product, the secondary bromide 9.3%, and the primary bromide only 0.5%. This high selectivity makes bromination synthetically useful for selectively functionalizing a particular position, whereas chlorination is generally too unselective for practical synthesis.
VI. Anti-Markovnikov Addition of HBr to Alkenes
While ionic (normal) addition of HBr to alkenes follows Markovnikov's rule, the presence of peroxides (ROOR) switches the regiochemistry to anti-Markovnikov. In this case, the hydrogen adds to the more substituted carbon and the bromine adds to the less substituted carbon. This reversal occurs exclusively with HBr and peroxides, not with HCl or HI.
The mechanism is a radical chain process. During initiation, the peroxide undergoes homolysis to generate alkoxy radicals, which then abstract a hydrogen from HBr to produce a bromine radical. In propagation step 1, the bromine radical adds to the less substituted carbon of the alkene, forming the more stable (more substituted) carbon radical. This step determines the regioselectivity. In propagation step 2, the carbon radical abstracts a hydrogen from HBr to produce the anti-Markovnikov product and regenerate the bromine radical.
The anti-Markovnikov regiochemistry arises because the bromine radical adds to generate the more stable radical intermediate, analogous to how Markovnikov selectivity in ionic addition is governed by the stability of the carbocation. The reason this reaction works only with HBr is thermodynamic: for HCl, the chlorine addition step is endothermic and unsustainable; for HI, the hydrogen abstraction step is endothermic. Only with HBr are both propagation steps exothermic, sustaining the chain.
<image>Panel A: Side-by-side comparison of ionic vs. radical HBr addition to propene. Ionic (no peroxides): H+ adds to C1, Br- adds to C2, giving 2-bromopropane (Markovnikov). Radical (with ROOR): Br radical adds to C1 (forming the more stable secondary radical at C2), then H is abstracted from HBr to give 1-bromopropane (anti-Markovnikov). Both mechanisms are drawn with appropriate arrows (curved for ionic, fishhook for radical). Panel B: Energy diagram for the radical propagation steps showing both steps are exothermic for HBr, with the transition state for Br addition reflecting the stability of the more substituted radical intermediate.</image>
VII. Radical Polymerization
Alkenes can undergo radical polymerization to form long-chain polymers, initiated by radical initiators such as benzoyl peroxide or AIBN. The initiation step generates a radical that adds to the first monomer unit. Propagation involves repeated addition of monomer to the growing radical chain end, building the polymer by thousands of monomer units. Termination occurs when two radical chain ends couple together or undergo disproportionation.
This process produces many of the most widely used polymers: polyethylene from ethylene, polystyrene from styrene, PVC from vinyl chloride, PMMA (Plexiglas) from methyl methacrylate, and Teflon (PTFE) from tetrafluoroethylene.
VIII. Other Radical Reactions
Allylic bromination with NBS (N-bromosuccinimide) selectively introduces a bromine atom at the allylic position, the carbon adjacent to a C=C double bond. NBS maintains a low, constant concentration of Br2, which is essential for selectivity. The mechanism proceeds through a resonance-stabilized allylic radical intermediate. Cyclohexene treated with NBS, for example, gives 3-bromocyclohexene.
Autooxidation is a radical chain reaction in which organic compounds react with molecular oxygen to form hydroperoxides (ROOH), preferentially at allylic and benzylic positions. This process is responsible for the rancidity of fats, the degradation of rubber, and the aging of plastics. Antioxidants such as BHT and vitamin E terminate radical chains by forming stable, resonance-delocalized phenoxy radicals, effectively halting the degradation process.
Combustion, the reaction of hydrocarbons with oxygen to produce CO2 and water, is itself a radical chain reaction that proceeds through many radical intermediates and releases large amounts of energy.
<image>Panel A: Allylic bromination of cyclohexene with NBS. The mechanism shows: initiation (Br2 → 2 Br.), propagation step 1 (Br. abstracts allylic H from cyclohexene to form resonance-stabilized allylic radical — both resonance structures drawn), propagation step 2 (allylic radical reacts with Br2 to give 3-bromocyclohexene and regenerate Br.). The role of NBS in maintaining low Br2 concentration is noted. Panel B: Structure of common antioxidants BHT and vitamin E (alpha-tocopherol), showing the phenolic OH group that donates an H atom to terminate radical chains, forming a stable, resonance-delocalized phenoxy radical.</image>
