Spring 2009

1. Spring 2009 Dr. Halligan CHM 236 Chapter 15 Radical Reactions 1 1

2. Introduction • A significant group of reactions involve radical intermediates. • A radical is a reactive intermediate with a single unpaired electron, formed by homolysis of a covalent bond. • A radical contains an atom that does not have an octet of electrons. • Half-headed arrows are used to show the movement of electrons in radical processes.

3. Introduction • Carbon radicals are classified as 1°, 2° or 3°. • A carbon radical is sp2 hybridized and trigonal planar, like sp2 hybridized carbocations. • The unhybridized p orbital contains the unpaired electron and extends above and below the trigonal planar carbon.

4. Introduction Figure 15.1 The relative stability of 1° and 2° carbon radicals

5. General Features of Radical Reactions • Radicals are formed from covalent bonds by adding energy in the form of heat () or light (h). • Some radical reactions are carried out in the presence of a radical initiator. • Radical initiators contain an especially weak bond that serves as a source of radicals. • Peroxides, compounds having the general structure RO—OR, are the most commonly used radical initiators. • Heating a peroxide readily causes homolysis of the weak O—O bond, forming two RO• radicals. • Radicals undergo two main types of reactions—they react with  bonds, and they add to  bonds.

6. Reaction of a Radical X• with a C-H Bond. • A radical X• abstracts a hydrogen atom from a C—H  bond to from H—X and a carbon radical. Reaction of a Radical X• with a C=C Bond. • A radical X• also adds to the  bond of a carbon—carbon double bond.

7. Two Radicals Reacting with Each Other. • A radical X•, once formed, rapidly reacts with whatever is available, usually a stable  or  bond. • Occasionally, two radicals react to form a sigma bond. • The reaction of a radical with oxygen (a diradical in its ground state electronic configuration) is another example of two radicals reacting with each other. • Compounds that prevent radical reactions from occurring are called radical inhibitors or radical scavengers. Besides O2, vitamin E and other related compounds are radical scavengers.

8. Chlorination and Bromination of Alkanes • Alkanes are not very reactive since they only contain strong s bonds. • The only two reactions that alkanes undergo are combustion and halogenation.

9. Chlorination and Bromination of Alkanes • In addition to combustion reactions, alkanes undergo halogenation. • These reactions take place only with heat (D) or in the presence of light (hn). • When subjected to high temperatures or light, Cl-Cl and Br-Br bonds will cleave homolytically to produce two radicals (initiation step). • If the goal is to maximize the yield of monohalogenated product, then an excess of alkane should be used.

10. Monochlorination of Alkanes *Monobromination follows the same mechanism.

11. Radical Stability follows the same trend a Carbocation Stability • Radicals are stabilized by hyperconjugation just like carbocations and so neighboring alkyl groups provide stabilization. • The stabilization for radicals derived through hyperconjugation is not as dramatic because there is an unpaired electron in an antibonding MO.

12. Factors that Determine Product Distribution • When more than one proton is available for abstraction, there will be a distribution of products. • The ratio of halogenated products depends on both probability (number of available hydrogens for abstraction) and the stability of the alkyl radical formed during the rate determining hydrogen abstraction step. • Radical stability follows the same order as carbocation stability.

13. Monochlorination of Butane • Consider the monochlorination of butane. • Experimentally, it is observed that 1-chlorobutane is produced in 29% and 2-chlorobutane is formed in 71% yield. • How can we predict this distribution? • Let’s calculate the product distribution based on probability and reactivity.

14. Bromine is much more selective

15. Why is bromine much more selective? • By comparing the DH values for chlorination and bromination, we see that bromination is a slower process and requires more energy.

16. Why is bromine much more selective? • These reaction coordinate diagrams help explain why radical bromination reactions are more selective. See if you can explain it.

17. Radical fluorination and iodination are not synthetically useful reactions.

18. Factors that Determine Product Distribution • When more than one proton is available for abstraction, there will be a distribution of products. • The ratio of halogenated products depends on both probability (number of available hydrogens for abstraction) and the stability of the alkyl radical formed during the rate determining hydrogen abstraction step. • Radical stability follows the same order as carbocation stability.

19. The Ozone Layer and CFCs • Ozone is vital to life, and acts as a shield, protecting the earth’s surface from harmful UV radiation. • Current research suggests that chlorofluorocarbons (CFCs) are responsible for destroying ozone in the upper atmosphere.

20. The Ozone Layer and CFCs • CFCs are inert, odorless, and nontoxic, and have been used as refrigerants, solvents, and aerosol propellants. • They are water insoluble and volatile, and readily escape into the upper atmosphere, where they are decomposed by high-energy sunlight to form radicals that destroy ozone by a radical chain mechanism.

21. The Ozone Layer and CFCs • The overall result is that O3 is consumed as a reactant and O2 is formed. • In this way, a small amount of CFC can destroy a large amount of O3. • New alternatives to CFCs are hydrochlorofluorocarbons (HCFCs) and hydrofluorocarbons (HFCs) such as CH2FCF3. • These compounds are decomposed by HO• before they reach the stratosphere and therefore they do not take part in the radical reactions resulting in O3 destruction.

22. The Ozone Layer and CFCs Figure 15.7 CFCs and the destruction of the ozone layer

23. Radical addition of HBr • If HBr is added in the presence of a peroxide, the reaction proceeds in an anti-Markovnikov fashion. • Take a look at the mechanism for an explanation for these results.

24. Radical addition of HBr

25. Radical addition of HBr • During propagation, the reaction continues because there is a radical present. • The reaction stops when the radicals are converted to stabled, paired electron species.

26. The Peroxide Effect • The Peroxide effect is only observed for reactions with HBr and peroxides, not with any of the other hydrogen halides and peroxides. • Both propagation steps are exothermic for the reaction of HBr/peroxides with an alkene.

27. Stereochemistry of Radical Substitution and Addition Reactions • In the following radical substitution reaction, a new asymmetric center is formed and thus gives rise to a pair of enantiomers. • Why are these two compounds a pair of enantiomers and not a pair of diastereomers?

28. Stereochemistry of Radical Substitution and Addition Reactions • In the following radical addition reaction of an alkene with HBr/peroxides, a new asymmetric center is generated. • Again, a racemic mixture is formed since there is only one chiral carbon in the product.

29. How Do We Explain the Stereochemistry of Radical Reactions? • A radical intermediate is similar to a carbocation in terms of geometry; it is planar (flat). • So, the next atom that attaches to the radical may approach from the front side or the back side, leading to two stereoisomers.

30. Radical Halogenation at an Allylic Carbon • An allylic carbon is a carbon adjacent to a double bond. • Homolysis of the allylic C—H bond in propene generates an allylic radical which has an unpaired electron on the carbon adjacent to the double bond. • The bond dissociation energy for this process is even less than that for a 30 C—H bond (91 kcal/mol). • This means that an allyl radical is more stable than a 30 radical.

31. Radical Halogenation at an Allylic Carbon • The allyl radical is more stable than other radicals because two resonance forms can be drawn for it.

32. Radical Halogenation at an Allylic Carbon • Because allylic C—H bonds are weaker than other sp3 hybridized C—H bonds, the allylic carbon can be selectively halogenated using NBS in the presence of light or peroxides. • NBS contains a weak N—Br bond that is homolytically cleaved with light to generate a bromine radical, initiating an allylic halogenation reaction. • Propagation then consists of the usual two steps of radical halogenation.

33. Radical Halogenation at an Allylic Carbon

34. Radical Halogenation at an Allylic Carbon • NBS also generates a low concentration of Br2 needed in the second chain propagation step (Step [3] of the mechanism). • The HBr formed in Step [2] reacts with NBS to form Br2, which is then used for halogenation in Step [3] of the mechanism.

35. Radical Halogenation at an Allylic Carbon Thus, an alkene with allylic C—H bonds undergoes two different reactions depending on the reaction conditions.

36. Radical Halogenation at an Allylic Carbon Question: Why does a low concentration of Br2 (from NBS) favor allylic substitution (over ionic addition to form the dibromide)? • Answer: • The key to getting substitution is to have a low concentration of bromine (Br2). • The Br2 produced from NBS is present in very low concentrations. • A low concentration of Br2 would first react with the double bond to form a low concentration of the bridged bromonium ion. • The bridged bromonium ion must then react with more bromine (in the form of Br¯) in a second step to form the dibromide. • If concentrations of both intermediates—the bromonium ion and Br¯ are low (as is the case here), the overall rate of addition is very slow, and the products of the very fast and facile radical chain reaction predominate.

37. Radical Halogenation at an Allylic Carbon • Halogenation at an allylic carbon often results in a mixture of products. Consider the following example: • A mixture results because the reaction proceeds by way of a resonance stabilized radical.

38. Radical Halogenation at an Allylic Carbon • Oils are susceptible to allylic free radical oxidation. Figure 15.8 The oxidation of unsaturated lipids with O2

39. Antioxidants • An antioxidant is a compound that stops an oxidation from occurring. • Naturally occurring antioxidants such as vitamin E prevent radical reactions that can cause cell damage. • Synthetic antioxidants such as BHT—butylated hydroxy toluene—are added to packaged and prepared foods to prevent oxidation and spoilage. • Vitamin E and BHT are radical inhibitors, so they terminate radical chain mechanisms by reacting with the radical.

40. Antioxidants • To trap free radicals, both vitamin E and BHT use a hydroxy group bonded to a benzene ring—a general structure called a phenol. • Radicals (R•) abstract a hydrogen atom from the OH group of an antioxidant, forming a new resonance-stabilized radical. This new radical does not participate in chain propagation, but rather terminates the chain and halts the oxidation process. • Because oxidative damage to lipids in cells is thought to play a role in the aging process, many anti-aging formulations contain antioxidants.

41. Polymers and Polymerization • Polymers are large molecules made up of repeating units of smaller molecules called monomers. They include biologically important compounds such as proteins and carbohydrates, as well as synthetic plastics such as polyethylene, polyvinyl chloride (PVC) and polystyrene. • Polymerization is the joining together of monomers to make polymers. For example, joining ethylene monomers together forms the polymer polyethylene, a plastic used in milk containers and plastic bags.

42. Polymers and Polymerization • Many ethylene derivatives having the general structure CH2=CHZ are also used as monomers for polymerization. • The identity of Z affects the physical properties of the resulting polymer. • Polymerization of CH2=CHZ usually affords polymers with Z groups on every other carbon atom in the chain.

43. Polymers and Polymerization

44. Polymers and Polymerization

45. Polymers and Polymerization • In radical polymerization, the more substituted radical always adds to the less substituted end of the monomer, a process called head-to-tail polymerization.