What are radicals? Radicals are intermediates with an unpaired electron Chapter 10 Radical Reactions H. Cl. Hydrogen radical Chlorine radical Methyl radical Often called free radicals Formed by homolytic bond cleavage Radicals are highly reactive, short-lived species Single-barbed arrows are used to show movement of single electrons Production of radicals Reactions of radicals Usually begins with homolysis of a relatively weak bond such as O-O or X-X Initiated by addition of energy in the form of heat or light Radicals seek to react in ways that lead to pairing of their unpaired electron Reaction of a radical with any species that does not have an unpaired electron will produce another radical Hydrogen abstraction is one way a halogen radical can react to pair its unshared electron Electronic structure of methyl radical Bond Dissociation Energies Atoms have higher energy (are less stable) than the molecules they can form 1. The formation of covalent bonds is exothermic 2. Breaking covalent bonds requires energy (i.e. is endothermic) The homolyticbond dissociation energy is abbreviated DH o 1
Bond Dissociation Energies and Heats of Reaction Example of using Bond Dissociation Energies Homolytic Bond Dissociation energies can be used to calculate the enthalpy change (DH o ) for a reaction Consider the possible reaction of H 2 with Cl 2 DH o is positive for bond breaking and negative for bond forming?h o = sum of DH o for products (-) and reactants (+) A negative heat of reaction means reaction is exothermic?h o is not dependant on the mechanism; only the initial and final states of the molecules are considered Reaction is exothermic, more energy is released in forming the 2 H-Cl bonds of product than is required to break the H-H and Cl-Cl bonds of reactants Table of bond dissociation energies in text, p. 430 A:B A. + B. Note X-X bonds are weak Relative stability of organic radicals Relative Stability of organic radicals Compare the DH o for the primary and secondary hydrogens in propane Using the same table, the tert-butyl radical is more stable than the isobutyl radical Diff = 22 kj/mol Diff = 10 kj/mol Since less energy is needed to form the isopropyl radical (from same starting material), the isopropyl radical must be more stable 2
Relative Stability of Free Radicals Energy diagrams for formation of radicals The relative stabilities of carbon radicals follows the same trend as for carbocations The most substituted radical is most stable Radicals are electron deficient, as are carbocations, and are therefore also stabilized by hyperconjugation The Reactions of Alkanes with Halogens Alkanesundergo substitution reactions with halogens (fluorine, bromine and chlorine) initiated by heat or light Chlorination Chlorination of higher alkanes leads to mixtures of monochlorinated product (and more substituted products) Radical halogenation can yield a mixture of halogenated compounds because all hydrogen atoms in an alkane are capable of substitution For example, all degrees of methane halogenation will be seen Monosubstitution can be achieved by using a large excess of the alkane Chlorine is relatively unselective and does not greatly distinguish between type of hydrogen If there were zero selectivity, the tertiary product would be 1/9 of the primary product, whereas it is actually 2/3 so there is a preference of about 5-fold Mechanism of Chlorination: a Chain Reaction The reaction mechanism has three distinct aspects: 1. Chain initiation 2. Chain propagation 3. Chain termination Chain initiation Step 1 Chlorine radicals form when the reaction mixture is subjected to heat or light Chlorination of Methane: Mechanism of Reaction Chain propagation (2 steps repeated many times) A chlorine radical reacts with a molecule of methane to generate a methyl radical A methyl radical reacts with a molecule of chlorine to yield chloromethane and regenerate chlorine radical The new chlorine radical reacts with another methane molecule, continuing the chain reaction Recall that the Cl-Cl bonds is relatively weak A single initiation step can lead to thousands of propagation steps, hence the term chain reaction 3
Electron flow in the mechanism Chain termination Occasionally the reactive radical intermediates are quenched by reaction pathways that do not generate new radicals The reaction of chlorine with methane requires constant irradiation to replace radicals quenched in chain-terminating steps Energy Changes in the Chlorination of Methane Bond Energies a good approximation of free energy changes Overall Free-Energy Change: DG o = DH o - T (DS o ) In radical reactions such as the chlorination of methane the overall entropy change (DS o ) in the reaction is small Thus DH o values closely approximate the DG o values The chain propagation steps have overall DH o = -101 kj mol -1 and are highly exothermic DG o = -102 kj mol -1 and DH o = -101 kj mol -1 for this reaction Activation Energies for Chlorination of Methane When using enthalpy values (DH o ) the term for the difference in energy between starting material and the transition state is the energy of activation (E act ) Recall when free energy of activation (DG o ) values are used this difference is DG For the chlorination of methane the E act values have been measured Energy of activation values can be predicted 1. A reaction in which bonds are broken will have E act > 0 even if a stronger bond is formed and the reaction is highly exothermic Bond forming always lags behind bond breaking 4
Energy of activation values can be predicted 2. An endothermic reaction which involves bond breaking and bond forming will always have E act > DH o 3. A gas phase reaction in which only bond homolysis occurs has DH o = E act 4. A gas phase reaction in which small radicals combine to form a new bond usually has E act = 0 Reaction of Methane with Other Halogens The order of reactivity of methane substitution with halogens is: fluorine > chlorine > bromine > iodine The order of reactivity is based on the values of E act for the first step of chain propagation and DH o for the entire chain propagation Fluorination Fluorination has a very low value for E act in the first step and DH o is extremely exothermic Fluorination reactions are explosive The energy values of the initiation step are unimportant since they occur so rarely On the basis of DH o values for X 2, the initiation step iodination should be most rapid Chlorination Chlorination is also highly exothermic overall, but more controllable with a higher value of E act and lower overall DH o values Bromination The bromine atom has a significant E act in the first step of propagation so the reaction is much more controllable and selective. Still exothermic overall 5
Iodination? Direct iodination is not a useful reaction Halogenation of Higher Alkanes Monochlorination of alkanes proceeds with limited selectivity Tertiary hydrogens roughly 5 times more reactive than primary Secondary hydrogens roughly 3.5 times more reactive than primary E act for abstraction of a tertiary hydrogen is slightly lower because of increased stability of the intermediate tertiary radical Chlorination occurs so rapidly it cannot distinguish well between classes of hydrogen and so is not very selective * 1. High E act in first propagation step means very few successful collisions 2. Overall reaction is endothermic Useful Chlorinations Chlorination is synthetically useful when molecular symmetry limits the number of possible substitution products Based on relative reactivitiesof 1:3.5:5 per H for 1 o, 2 o, 3 o H s, predicted product ratios would be 29: 24: 33: 14 Cl 2 heat o r UV Cl Selectivity of Bromine Bromine is much less reactive but more selective than chlorine in radical halogenation Would fluorination be selective? Fluorine shows almost no discrimination in replacement of hydrogens because it is so reactive So reactive that only per fluoro compounds (all H replaced by F) are made via direct fluorination (and then very carefully) Bromination can be a practical method to make alkyl bromides, whenever one potential radical is more stable than the others 6
Summary of halogenation of alkanes Stereochemistry and halogenation If a radical is formed at a single chiral center, the product is racemic H Br2 UV Br (R) Racemic (1:1 R + S) C Demonstrates that radical must be planar with equal faces (or so rapidly inverting that all memory of chirality is lost) Reactions that Generate Tetrahedral Stereogenic Carbons A reaction of achiral starting materials which produces a product with a stereogenic carbon will produce a racemic mixture Generation of a Second StereogenicCarbon When a molecule with one or more stereogenic carbons reacts to create another stereogenic carbon, the two diastereomeric products are not produced in equal amounts. The intermediate radical is chiral and and reactions on the two faces of the radical are not equally likely Anti-Markovnikov Addition of HBr to Alkenes Addition of hydrogen bromide in the presence of peroxides gives anti-markovnikovaddition Mechanism for the Anti -Markovnikov Addition of HBr A free radical chain mechanism Steps 1 and 2 of the mechanism are chain initiation steps which produce a bromine radical Works only for HBr: the other hydrogen halides do not give this type of anti-markovnikov addition 7
In step 3, the first step of propagation, a bromine radical adds to the double bond to give the most stable of the two possible carbon radicals (in this case, a 2 o radical) Attack at the 1 o carbon is also less sterically hindered Step 4 regenerates a bromine radical Why the anti-markovnikov Addition? In the first propagation step, the addition of Br to the double bond, there are two possible paths: 1. Path [A] forms the less stable 1 0 radical 2. Path [B] forms the more stable 2 0 radical The more stable 2 0 radical forms faster, so Path [B] is preferred. The new bromine radical reacts with another equivalent of alkene, and steps 3 and 4 repeat in a chain reaction Controlling Addition of HBr to Alkenes Early studies of HBr addition gave contradictory results sometimes Markovnikov addition and sometime anti-markovnikov Radical Polymerization of Alkenes Polymers are macromolecules made up of repeating subunits The subunits used to synthesize polymers are called monomers Polyethylene is made of repeating subunits derived from ethylene Polyethylene is called a chain-growth polymer or addition polymer n= large number To favor normal addition, remove possible traces of peroxides from the alkene and use a polar, protic solvent To favor anti-mark, add peroxide and use non-polar solvent Polystyrene is made in an analogous reaction using styrene as the monomer Very useful for your synthetic tool box Initiator used to start a chain reaction mechanism A very small amount of diacyl peroxide is added in initiating the reaction so that few, but very long polymer chains are obtained Chain termination Chain growth can terminate by combination of two radicals or by disproportionation (abstracting a H from the ß-carbon of the growing radical of another chain) Produces an alkyl radical to initiate chain The propagation step simply adds more ethylene molecules to a growing chain 8
Chain branching Some other addition polymers from common alkenes Chain branching can occur by abstraction of a hydrogen atom on the same chain and continuation of growth from the main chain backbiting This cross-linking of polymer chain will modify properties of the polymer by stiffening its flexibility Note the regular alternation of the Z groups, called head to tail, since the addition step always produces the more stable radical Some common Polymers Superglue Some monomers can also be polymerized by nucleophiles Molecular oxygen is a diradical Each oxygen has 6 electrons in outer shell = 12 Bonding orbitals accommodate the first ten, but last two go one each into degenerate anti-bonding orbitals Oxygen readily oxides many organic molecules Fast oxidation = combustion Slow oxidation = auto-oxidation at activated sites of polyunsaturated compounds, ethers and some biomolecules Other reactive forms of oxygen: Singlet oxygen Superoxide (O 2.- = an anion radical) Ozone (O 3 ) 9
Antioxidants Naturally occurring antioxidants such as vitamin E prevent radical reactions that can cause cell damage. Synthetic antioxidants such as BHT 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. 10