Radical Chain Mechanism • Chain initiation: A step in a chain reaction characterized by formation of reactive intermediates (radicals, anions, or cations) from nonradical or noncharged molecules.
Radical Chain Mechanism • 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:The number of times the cycle of chain propagation steps repeats in a chain reaction.
Radical Chain Mechanism • Chain termination: A step in a chain reaction that involves destruction of reactive intermediates.
Chain Propagation Steps • For any set of chain propagation steps, their • equations add to the observed stoichiometry. • enthalpies add to the observed H0.
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)?
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.
Hammond’s Postulate • (a) A highly exothermic reaction • (b) A highly endothermic reaction
Hammond’s Postulate • In the halogenation of an alkane, hydrogen abstraction (the rate-determining step) is exothermic for chlorination but endothermic for bromination
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.
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.
Hammond’s Postulate • Transition states and energetics for hydrogen abstraction in the radical chlorination and bromination of 2-methylpropane (isobutane).
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 sp2 hybridized and the unpaired electron occupies the unhybridized 2p orbital (see next screen).
Stereochemistry • Radical bromination of butane.
Allylic Halogenation • Allylic carbon:A C adjacent to a C-C double bond. • Allylic hydrogen: An H on an allylic carbon. • an allylic C-H bond is weaker than a vinylic C-H bond.
Allylic Bromination • Allylic bromination using NBS
Allylic Bromination • A radical chain mechanism • Chain initiation • Chain propagation
Allylic Bromination • chain termination • NBS neutralizes HBr and the protonated amide then provides Br2 for the chain process.
The Allyl Radical • A hybrid of two equivalent contributing structures.
The Allyl Radical • Molecular orbital model of the allyl radical. Combination of three 2p orbitals gives three p molecular orbitals.
The Allyl Radical • Unpaired electron spin density map of the allyl radical • Unpaired electron density (green cones) appears only on carbons 1 and 3
Allylic Halogenation • Problem Account for the fact that allylic bromination of 1-octene by NBS gives these isomeric products
Radical Autoxidation • Autoxidation: Oxidation requiring oxygen, O2, 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.
Radical Autoxidation • Autoxidation begins when a radical initiator, X•, abstracts a doubly allylic hydrogen. • This radical is stabilized by resonance with both double bonds.
Radical Autoxidation • The doubly allylic radical reacts with O2, 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.
Radical Autoxidation • vitamin E as an antioxidant
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.
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
Radical Addition of HBr to Alkenes • Chain propagation
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.
Haloalkanes End Chapter 8