Radical Substitution Reaction Mechanisms

Radical substitution reactions by iodine are not practical because the abstraction of hydrogen from hydrocarbons by iodine is endothermic, even for stable radicals. The enthalpy of the overall reaction is also slightly endothermic. Thus, because of both the kinetic problem excluding a chain reaction and an unfavorable equilibrium constant for substitution, iodination cannot proceed by a radical-chain mechanism. 

In this chapter, we discuss free-radical substitution reactions. Free-radical additions to unsaturated compounds and rearrangements are discussed in Chapters 15 and 18, respectively. In addition, many of the oxidation-reduction reactions considered in Chapter 19 involve free-radical mechanisms. Several important types of free-radical reactions do not usually lead to reasonable yields of pure products and are not generally treated in this book. Among these are polymerizations and high-temperature pyrolyses. 

It is assumed that all similar fluorination reactions proceed via an intricate radical chain-reaction mechanism. The overall reactions for the substitution of hydrogen by fluorine (RH + F2 - RF + HF, AH298 -430 kJ/mol per carbon atom) are more exothermic than the reactions for adding fluorine to the double bonds... 

Bromination of alkanes follows the same mechanism as chlorination. The only difference is the reactivity of the radical i.e., the chlorine radical is much more reactive than the bromine radical. Thus, the chlorine radical is much less selective than the bromine radical, and it is a useful reaction when there is only one kind of hydrogen in the molecule. If a radical substitution reaction yields a product with a chiral centre, the major product is a racemic mixture. For example, radical chlorination of n-butane produces a 71% racemic mixture of 2-chlorobutane, and bromination of n-butane produces a 98% racemic mixture of 2-bromobutane. 

A study of die addition reactions of radicals to fiillerenes (C60/C70) by EPR has appeared and die dynamic effects in the EPR spectra of fidlerenyl radicals due to hindered rotation and the multi-addition of radicals to fidlerenes are described.9 Other review articles which have appeared this year include recent advances in the radical substitution reactions of alkyl, aryl, and vinyl halides10 and the substitution and photochemical reactions of heterocyclic A -oxidcs.11 The mechanisms for the oxidation of hydrocarbons, lipids, and low-density lipoproteins have been reviewed.12... 

Evidence of both types of potential intermediate in reduction by Sml2, the alkyl radical and the ketyl radical 27, has been provided by radical cyclisation reactions. Mechanism 4, which involves an Sjj2 substitution, has been eliminated because optically active halides are completely racemised. The rate of addition of alkyl radicals to ketones is very slow (<102 dm3 mol-1 s-1) the resulting alkoxy radicals (26) are very reactive and could not... 

The potential energy surfaces for the attack of a hydrogen atom and of a methyl radical at the heteroatom in MH4 and H3CMH3 (M = Si, Ge and Sn) (equations 45, 46 and 47)498a and the attack of MH3 on F M M" (M, M and M" are Si, Ge and Sn) (equation 48)498b were studied in order to provide a better understanding of the parameters which affect and control the mechanism of such radical substitution reactions. Calculations for substitutions at lead are not available. 

In the presence of light or heat, alkanes react with halogens to form alkyl halides. Haiogenation is a radical substitution reaction, because a halogen atom X replaces a hydrogen via a mechanism that involves radical intermediates. 

A very common second step in radical substitution reactions is for the initial free radical to react with a hydrogen atom of the organic reagent, and, after abstracting this hydrogen atom, to produce a carbon radical. Write down the balanced equation for the reaction of a chlorine radical with a methane molecule, and then write down the mechanism. 

Radicals have an unpaired electron and are usually electrically neutral. Accordingly, radical substitution reactions tend not to be affected by those factors, such as solvent polarity, that affect mechanisms involving charged species, such as nucleophilic or electrophilic substitution. 

The mechanism of photoinduced oxidation of aromatic compounds mediated by Ti02 in aqueous media is demonstrated by the reaction of 4-chlorophenol (601). Its degradation is principally based on oxidation by photocatalytically produced hydroxyl radicals, most likely adsorbed on the surface of a semiconductor catalyst.1554,1555 The initial reaction affords a 4-chlorodihydroxycyclodienyl radical 602, which releases the chlorine atom to form hydroquinone in a radical substitution reaction or loses the hydrogen atom via... 

In the Hofmann-Loejfler-Freytag reaction, an Af-chloroammonium ion is converted by a free-radical substitution reaction into a 4-chloroalkylammonium ion, which then undergoes intramolecular Sn2 substitution to give a pyrrolidine. In the free-radical substitution mechanism, the abstraction step occurs in an intramolecular fashion. Entropic and stereoelectronic factors make the regioselec-tivity very high for the C4 hydrogen. 

The two types of reaction follow different reaction mechanisms. Side-chain chlorination occurs by a radical chain reaction mechanism, nuclear chlorination by electrophilic substitution. 

Alkanes undergo radical substitution reactions with CI2 or Bt2 in the presence of heat or light (Sections 13.2-13.5). The mechanisms of the reaction are shown on pages 558 and 559. 

Radical substitution reactions and their mechanisms and applications have been reviewed several times [189,190]. Thiophene participates well in radical reactions. There are reviews describing both unimolecular radical nucleophilic substitutions (SrnI) [191] and homolytic aromatic substitutions (HAS) of thiophenes [192]. The formation of thiophene radicals from peroxides, thienylamines and iodothiophenes has been discussed [192]. 

Substitution reactions involving aryl radicals have been quite important in synthesis. The reason, in part, is that the resistance of aryl halides and related compounds to nucleophilic substitution greatly restricts the utility of Sn2 processes for synthetic purposes. Radical substitution reactions can be carried out with any of the sources of aryl radicals mentioned in Section 12.1.4, but acylnitrosoanilines and aryl diazonium compounds have been most widely used in synthesis. The decomposition of acylnitrosoanilines is a relatively complex process. The principal points of evidence supporting the mechanism shown below have been briefly reviewed ... 

Pyrolysis of 3-(o-azidophenyl)pyridine gives a- and y-carboline. Although the process does not formally involve a free radical ( N.GeH4. C5H4N), it is reminiscent of a radical substitution. The mechanism of the Graebe-Ullmann reaction, the formation of carbazoles by the pyrolysis of 3-arylbenzotriazoles, has not been elucidated, but some examples of it, notably the formation of carbolines from 3-pyridylbenzotriazoles, suggest the character of a radical substitution. 

Some mechanisms of electrophilic and radical substitution reactions Electrophilic substitution reactions have been proposed to occur by a general reaction path in which the attacking electrophilic group interacts first with the iron atom [287]. 

Addition to the Double Bond. Chlorine, bromine, and iodine react with aHyl chloride at temperatures below the inception of the substitution reaction to produce the 1,2,3-trihaLides. High temperature halogenation by a free-radical mechanism leads to unsaturated dihalides CH2=CHCHC1X. Hypochlorous and hypobromous acids add to form glycerol dihalohydrins, principally the 2,3-dihalo isomer. Dehydrohalogenation with alkah to epicbl orobydrin [106-89-8] is ofgreat industrial importance. 

Reaction Mechanism. High temperature vapor-phase chlorination of propylene [115-07-17 is a free-radical mechanism in which substitution of an allyhc hydrogen is favored over addition of chlorine to the double bond. Abstraction of allyhc hydrogen is especially favored since the allyl radical intermediate is stabilized by resonance between two symmetrical stmctures, both of which lead to allyl chloride. 

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