8-1 Radical Chain Mechanism  Chain initiation:  Chain initiation: A step in a chain reaction characterized by formation of reactive intermediates (radicals, anions, or cations) from nonradical or noncharged molecules.

8-2 Radical Chain Mechanism  Chain propagation:  Chain propagation: A step in a chain reaction characterized by the reaction of a reactive intermediate and a molecule to form a new radical or reactive intermediate and a new molecule.  Chain length:  Chain length: The number of times the cycle of chain propagation steps repeats in a chain reaction.

8-3 Radical Chain Mechanism  Chain termination:  Chain termination: A step in a chain reaction that involves destruction of reactive intermediates.

8-4 Chain Propagation Steps  For any set of chain propagation steps, their equations add to the observed stoichiometry. enthalpies add to the observed  H 0.

8-5 Regioselectivity?  The regioselectivity of chlorination and bromination can be accounted for in terms of the relative stabilities of alkyl radicals (3° > 2° > 1° > methyl).  But how do we account for the greater regioselectivity of bromination (1600:80:1) compared with chlorination (5:4:1)?

8-6 Hammond’s Postulate  Hammond’s Postulate:  Hammond’s Postulate: The structure of the transition state: for an exothermic step is reached relatively early in the reaction, and resembles the reactants of that step more than the products. for an endothermic step is reached relatively late in the reaction and resembles the products of that step more than the reactants.  This postulate applies equally well to the transition state for one-step reactions and to each transition state in a multi-step reaction.

8-7 Hammond’s Postulate  (a) A highly exothermic reaction  (b) A highly endothermic reaction

8-8 Hammond’s Postulate In the halogenation of an alkane, hydrogen abstraction (the rate- determining step) is exothermic for chlorination but endothermic for bromination

8-9 Hammond’s Postulate  Because hydrogen abstraction for chlorination is exothermic, the transition state resembles the alkane and a chlorine atom. there is little radical character on carbon in the transition state. regioselectivity is only slightly influenced by radical stability.

8-10 Hammond’s Postulate  Because hydrogen abstraction for bromination is endothermic, the transition state resembles an alkyl radical and HBr there is significant radical character on carbon in the transition state. regioselectivity is greatly influenced by radical stability. radical stability is 3° > 2° > 1° > methyl, and regioselectivity is in the same order.

8-11 Hammond’s Postulate  Transition states and energetics for hydrogen abstraction in the radical chlorination and bromination of 2-methylpropane (isobutane).

8-12 Stereochemistry  When radical halogenation produces a chiral center or takes place at a hydrogen on a chiral center, the product is a racemic mixture of R and S enantiomers. For simple alkyl radicals, the carbon bearing the radical is sp 2 hybridized and the unpaired electron occupies the unhybridized 2p orbital (see next screen).

8-13 Stereochemistry  Radical bromination of butane.

8-14 Allylic Halogenation  Allylic carbon:  Allylic carbon: A C adjacent to a C-C double bond.  Allylic hydrogen:  Allylic hydrogen: An H on an allylic carbon. an allylic C-H bond is weaker than a vinylic C-H bond.

8-15 Allylic Bromination  Allylic bromination using NBS

8-16 Allylic Bromination  A radical chain mechanism Chain initiation Chain propagation

8-17 Allylic Bromination chain termination  NBS neutralizes HBr and the protonated amide then provides Br 2 for the chain process.

8-18 The Allyl Radical  A hybrid of two equivalent contributing structures.

8-19 The Allyl Radical  Molecular orbital model of the allyl radical. Combination of three 2p orbitals gives three  molecular orbitals.

8-20 The Allyl Radical  Unpaired electron spin density map of the allyl radical Unpaired electron density (green cones) appears only on carbons 1 and 3

8-21 Allylic Halogenation ProblemProblem Account for the fact that allylic bromination of 1-octene by NBS gives these isomeric products

8-22 Radical Autoxidation  Autoxidation:  Autoxidation: Oxidation requiring oxygen, O 2, and no other oxidizing agent. Occurs by a radical chain mechanism similar to that for allylic halogenation. In this section, we concentrate on autoxidation of the hydrocarbon chains of polyunsaturated triglycerides. The characteristic feature of the fatty acid chains in polyunsaturated triglycerides is the presence of 1,4- dienes. Radical abstraction of a doubly allylic hydrogen of a 1,4-diene forms a particularly stable radical.

8-23 Radical Autoxidation Autoxidation begins when a radical initiator, X, abstracts a doubly allylic hydrogen. This radical is stabilized by resonance with both double bonds.

8-24 Radical Autoxidation The doubly allylic radical reacts with O 2, itself a diradical, to form a peroxy radical. The peroxy radical then reacts with another 1,4-diene to give a new radical, R, and a hydroperoxide. Vitamin E, a naturally occurring antioxidant, reacts preferentially with the initial peroxy radical to give a resonance-stabilized phenoxy radical, which is very unreactive, and scavenges another peroxide radical.

8-25 Radical Autoxidation vitamin E as an antioxidant

8-26 Radical Addition of HBr to Alkenes  Addition of HBr to alkenes gives either Markovnikov addition or non-Markovnikov addition depending on reaction conditions. Markovnikov addition occurs when radicals are absent. non-Markovnikov addition occurs when peroxides or other sources of radicals are present.

8-27 Radical Addition of HBr to Alkenes Addition of HCl and HI gives only Markovnikov products. To account for the the non-Markovnikov addition of HBr in the presence of peroxides, chemists proposed a radical chain mechanism.  Chain initiation

8-28 Radical Addition of HBr to Alkenes  Chain propagation

8-29 Radical Addition of HBr to Alkenes  Chain termination  This pair of reactions illustrates how the products of a reaction can be changed by a change in experimental conditions. Polar addition of HBr is regioselective, with protonation of the alkene preceding the addition of Br - to the more substituted carbon. Radical addition of HBr is also regioselective, with Br adding to the less substituted carbon.

8-30 Haloalkanes End Chapter 8