Homolytic Free-Radical Reactions

The chemistry of the high-temperature conversion and transformation processes of hydrocarbons is based on homolytic (free-radical) processes.933 

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The broadest classification of reactions is into the categories of heterolytic and homolytic reactions. In homolytic (free radical) reactions, bond cleavage occurs with one electron remaining with each atom, as in... 

Heterolytic reactions can be distinguished from homolytic (free radical) reactions by the following criteria ... 

There is now good reason to believe that homolytic (free radical) reactions are not involved. Therefore, the chemical mechanism underlying the kinetic process controlled by k must fall into one of the following three categories. All the intermediates shown are enzyme bound. 

Supercritical fluid (SCF) solvents are unique in that their densities can be varied continuously from gas-like to liquid-like values simply by varying the thermodynamic conditions. Because many of a fluid s solvating properties are strongly dependent on the fluid density, such large changes in density can have dramatic effects on solute reactivity [1,2]. For example, at low pressures supercritical water supports homolytic, free radical reactions, whereas at higher pressures, heterolytic, ionic reactions dominate [3,4]. Thus, thermodynamic control of SCF solvent densities promises to enable us to control reaction outcome and selectively produce desired products. 

A free-radical reaction is a chemical process which involves molecules having unpaired electrons. The radical species could be a starting compound or a product, but the most common cases are reactions that involve radicals as intermediates. Most of the reactions discussed to this point have been heterolytic processes involving polar intermediates and/or transition states in which all electrons remained paired throughout the course of the reaction. In radical reactions, homolytic bond cleavages occur. The generalized reactions shown below illustrate the formation of alkyl, vinyl, and aryl free radicals by hypothetical homolytic processes. 

Molecules in heterolytic (polar) reactions form and break bonds by "coordination" and molecules in homolytic (nonpolar or free radical) reactions form and break bonds by "colligation."75 (Two more new terms ) Heterolytic reactions occur mostly in solutions, usually involving ion formation and electrophilic or nucleophilic reactions homolytic reactions occur mostly in gases and do not involve ions because less energy is required to distance the atoms into neutral radicals.76... 

It would be useful to classify reactions as to their type, heterolytic (ionic) or homolytic (free radical), radical cation, or radical anion. Below are a number of examples of these types of reaction. 

Competition between Homolytic and Heterolytic Catalytic Decompositions of Hydroperoxides Reactions of Transition Metals with Free Radicals Reactions of Transition Metal Ions with Dioxygen Catalytic Oxidation of Ketones Cobalt Bromide Catalysis Oscillating Oxidation Reactions... 

Free radical reactions Once thought to be rare, the homolytic cleavage of covalent bonds to generate free radicals has now been found in a range of biochemical processes. Some examples are the reactions of methyl-malonyl-CoA mutase (see Box 17-2), ribonucleotide reductase (see Fig. 22-41), and DNA photolyase (see Fig. 25-25). 

Homolytic (free-radical) substitution may occur in any of the 2 to 6 positions of pyridine. Thus, the reaction of pyridine with benzene-diazonium salts gives a mixture of 2-, 3-, and 4-phenylpyridine. 

The free-radical reaction is ordinarily initiated by a homolytic bond cleavage (Equation 9.1). The radicals may then undergo various processes, for example... 

Initiation normally requires molecules with weak bonds to undergo homolytic cleavage to produce free radicals. Since bond homolysis even of weak bonds is endothermic, energy in the form of heat (A) or light (hv) is usually required in die initiation phase. However, some type of initiation is required to get any free-radical reaction to proceed. That is, you must first produce free radicals from closed-shell molecules in order to get free-radical reactions to occur. Benzoyl peroxide contains a weak 0-0 bond that undergoes thermal cleavage and decarboxylation (probably a concerted process) to produce phenyl radicals which can initiate free-radical chain reactions. 

Most free-radical reactions of synthetic value are chain reactions, the key steps of which are illustrated in Scheme 4.1. In the initiation step, a reactive radical is generated from a nonradical precursor (initiator). In many cases, this can be accomplished thermally. For instance, peroxides possess a weak oxygen-oxygen bond and, consequently, undergo homolytic dissociation upon heating ROOR —> 2RO . Free radicals can also be generated photochemically, radiolytically, or by electron transfer from appropriate precursors. 

On the contrary, most homolytical free-radical processes display formation of reactive intermediates capable of reacting by various reaction channels, which reduces the industrial value of these processes. 

The reaction chemistry of simple organic molecules in supercritical (SC) water can be described by heterolytic (ionic) mechanisms when the ion product 1 of the SC water exceeds 10" and by homolytic (free radical) mechanisms when <<10 1 . For example, in SC water with Kw>10-11 ethanol undergoes rapid dehydration to ethylene in the presence of dilute Arrhenius acids, such as 0.01M sulfuric acid and 1.0M acetic acid. Similarly, 1,3 dioxolane undergoes very rapid and selective hydration in SC water, producing ethylene glycol and formaldehyde without catalysts. In SC methanol the decomposition of 1,3 dioxolane yields 2 methoxyethanol, il lustrating the role of the solvent medium in the heterolytic reaction mechanism. Under conditions where K klO"11 the dehydration of ethanol to ethylene is not catalyzed by Arrhenius acids. Instead, the decomposition products include a variety of hydrocarbons and carbon oxides. 

Dramatic changes occur when the temperature of the SC water is raised to 500° C at constant pressure (P=0.144 g/cm3). Decreases in the dielectric constant to a value of 2 and ion product to 2.1 x 10- u cause the fluid to lose its water-like characteristics and behave as a high temperature gas. Under these conditions homolytic (free radical) bond cleavages are expected to dominate the reaction chemistry. Thus by using the engineering parameters of... 

FIGURE 69. Optimized transition states at MP2 for the homolytic free-radical substitution reactions shown in Figure 68 of hydridotellurides HTeEFl3 (E = Si, Ge, Sn) and HTeSi(SiFl3)3 with alkyl groups. Bond distances are in A. The calculated activation energies (kcalmol-1) at QCISD//MP2 refer to the forward reaction (A/i 1 ) and the reverse reaction (A 2 ) respectively. Reprinted from Reference 189 with permission from Elsevier Science... 

The homolytic cleavage of the carbon-selenium bond provides an easy access to radicals, which can undergo various subsequent reactions. The plethora of radical chemistry is accessible using selenium-containing compounds and examples of free-radical reactions are described in Section 9.11.2.4. 

A free-radical reaction usually begins with an initiation step in which the initiator undergoes homolytic (free-radical) cleavage to give two radicals. 

The use of light with bromine suggests a free-radical reaction, with light providing the energy for dissociation of Br2- This homolytic cleavage initiates the chain reaction by generating two Br- radicals. 

Peroxides are often added to free-radical reactions as initiators because the oxygen-oxygen bond cleaves homolytically rather easily. For example, the bond-dissociation enthalpy of the O —O bond in hydrogen peroxide (H —O —O —H) is only 213 kJ/mol (51 kcal/mol). Give a mechanism for the hydrogen peroxide-initiated reaction of cyclopentane with chlorine. The BDE for HO — Cl is 210 kJ/mol (50 kcal/mol). 

J. A. M. Simoes, A. Greenberg, and J. F. Lieberman (eds.) Energetics and Reactivities of Organic Free Radical Reactions, Kluwer, Dordrecht/Netherlands, 1996, Vol. 4, p. 224 Chem. Abstr. 125, 274936t (1996). [166] See also reference [28], chapter IX, concerning homolytic reactions, and references cited therein. [167] K. Ziegler, P. Orth, and K. Weber, Liebigs Ann. Chem. 504, 131 (1933) ... 

The ease of fission of the S H bond under homolytic conditions means that thiols are often used as hydrogen donors in free radical reactions. 

Imidazoles normally undergo free-radical reactions at the 2-position. For example, homolytic free-radical alkylation of histidines and histamines yields 2,3-disubstituted histidines and histamines. In these reactions, the free radical was generated via silver-catalyzed oxidative decarboxylation of acids with peroxydisulfate 433 (Scheme 103) <2001BML1133>. 

A few monographs have been dedicated to free radical reactions including fubstitutions. The most important are those by Williams [113] and Sosnovsky [114] and a review article has appeared concerning the homolytic substitution fnitro compounds [115]. 

Probably the best-known example of a free-radical reaction is the halogenation of alkanes with Br2 or NBS. This chain reaction is initiated by homolytic cleavage of Br2 induced by light. The propagation part consists of two atom abstraction reactions. 

Because of their high tolerance for numerous functionalities, tin hydrides have proved to be invaluable reagents in such simple chemical reactions as the reduction of functional groupsand in many other reactions which proceed via free radical mechanisms. Such has been the reliance on using organotin reagents in free radical chemistry that when efficient homolytic reactions are described without the use of tin reagents, the work is frequently published with phrases such as tin-free radical reactions in the title ... 

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