Radical reactions examples

To meet the needs of the advanced students, preparations have now been included to illustrate, for example, reduction by lithium aluminium hydride and by the Meerwein-Ponndorf-Verley method, oxidation by selenium dioxide and by periodate, the Michael, Hoesch, Leuckart and Doebner-Miller Reactions, the Knorr pyrrole and the Hantzsch collidine syntheses, various Free Radical reactions, the Pinacol-Pinacolone, Beckmann and Arbusov Rearrangements, and the Bart and the Meyer Reactions, together with many others. 

The free radicals that we usually see in carbon chemistry are much less stable than these Simple alkyl radicals for example require special procedures for their isolation and study We will encounter them here only as reactive intermediates formed m one step of a reaction mechanism and consumed m the next Alkyl radicals are classified as primary secondary or tertiary according to the number of carbon atoms directly attached to the carbon that bears the unpaired electron... 

A typical example of a nonpolymeric chain-propagating radical reaction is the anti-Markovnikov addition of hydrogen sulfide to a terminal olefin. The mechanism involves alternating abstraction and addition reactions in the propagating steps ... 

This reaction is one example of several possible radical transition-metal ion interactions. The significance of this and similar reactions is that radicals are destroyed and are no longer available for initiation of useful radical reactions. Consequentiy, the optimum use levels of transition metals are very low. Although the hydroperoxide decomposes quickly when excess transition metal is employed, the efficiency of radical generation is poor. 

There are many chemical methods for generating radicals reported in the hterature that do not involve conventional initiators. Specific examples are included in References 64—79. Most of these radical-generating systems carmot broadly compete with the use of conventional initiators in industrial polymer apphcations owing to cost or efficiency considerations. However, some systems may be weU-suited for initiating specific radical reactions or polymerizations, eg, grafting of monomers to cellulose using ceric ion (80). 

Nitroxyl radicals of diarylamines can also be obtained on oxidation with hydrogen peroxide in the presence of vanadium ions. Resonance helps stabili2e these radicals. Eor example, the nitroxide from 4,4 -dimethoxydiphenylainine [63619-50-1] is stable for years, whereas the radical from the unsubstituted diphenylamine caimot be isolated. Substitution in the ortho and para positions also increases the stabiUties of these nitroxides by inhibiting coupling reactions at these sites. However, they are not as stable as the stericaHy hindered tetramethylpiperidyl radical. 

Kinetic Models Used for Designs. Numerous free-radical reactions occur during cracking therefore, many simplified models have been used. For example, the reaction order for overall feed decomposition based on simple reactions for alkanes has been generalized (37). 

The use of free-radical reactions for this mode of ring formation has received rather more attention. The preparation of benzo[Z)]thiophenes by pyrolysis of styryl sulfoxides or styryl sulfides undoubtedly proceeds via formation of styrylthiyl radicals and their subsequent intramolecular substitution (Scheme 18a) (75CC704). An analogous example involving an amino radical is provided by the conversion of iV-chloro-iV-methylphenylethylamine to iV-methylindoline on treatment with iron(II) sulfate in concentrated sulfuric acid (Scheme 18b)(66TL2531). 

Similar reactions occur with acyl radicals, for example with the CONH2 radical from formamide (74AHC(16)123). 

Recent development of techniques for measuring the rates of very fast reactions has permitted absolute rates to be measured for some fundamental types of free-radical reactions. Some examples of absolute rates and values are given in Table 12.2. 

Nevertheless, many free-radical processes respond to introduction of polar substituents, just as do heterolytic processes that involve polar or ionic intermediates. The substituent effects on toluene bromination, for example, are correlated by the Hammett equation, which gives a p value of — 1.4, indicating that the benzene ring acts as an electron donor in the transition state. Other radicals, for example the t-butyl radical, show a positive p for hydrogen abstraction reactions involving toluene. ... 

The final step is not a radical reaction, but an example of the Baeyer-Villiger reaction, which will be discussed in Section 12.5.2 of Part B. 

One of the older preparative free-radical reactions is the addition of polyhalomethanes to alkenes. Examples of addition of carbon tetrabromide, carbon tetrachloride, and bromoform have been recorded. The reactions are chain processes that depend on facile abstraction of halogen or hydrogen from the halomethane ... 

The major organic reactions of BrCl consist of electrophilic brominations of aromatic compounds. Many aromatic compounds do not react in aqueous solution unless the reaction involves activated aromatic compounds (an example being phenol). Bromine chloride undergoes free-radical reactions more readily than bromine. 

In radical reactions not involving bromine or chlorine on the substrate, rearrangements are much rarer One example is the fluorination of di-tert butyl ketone which produces perfluormated / rt-buty isobutyl ketone [J5] Although isolated yields are poor only the rearranged ketone could be isolated This is perhaps only the second example of a 1,2-acyl shift Low fluorine substrate ratios show that this rearrangement occurs after monofluorination... 

Application of radical reactions to organic synthesis has recently received much atrendon, and various important reacdons have been discovered in this field. Alkyl halides, sulfides, seleniJes, and thiocarbonyl compounds have been used as precursors to alkyl radicals. Some examples are illustrated in Scheme 7.18. ... 

As an example of an industrially useful radical reaction, look at the chlorination of methane to yield chloromethane. This substitution reaction is the first step in the preparation of the solvents dichloromethane (CHoCl ) and chloroform (CHCI3). 

In biological reactions, the situation is different from that in the laboratory. Only one substrate molecule at a time is present in the active site of the enzyme where reaction takes place, and that molecule is held in a precise position, with coenzymes and other necessary reacting groups nearby. As a result, biological radical reactions are both more controlled and more common than laboratory or industrial radical reactions. A particularly impressive example occurs in the biosynthesis of prostaglandins from arachiclonic acid, where a sequence of four radical additions take place. The reaction mechanism was discussed briefly in Section 5.3. 

On the basis of the examples addressed thus far, it is clear that radical reactions can accomplish manifold transformations in organic synthesis. One of the outstanding achievements of synthetic radical chemistry is the development of synthetic strategies based on controlled, tandem radical cyclizations. The efficiency of such strategies is exemplified in the substantial and elegant synthetic work of D. P. Curran and his group.54 The remainder of this chapter will address the concise total syntheses of ( )-hirsutene [( )-1]55 and ( )-A9(12)-capnellene [( )-2]56 by the Curran group. 

A radical polymerization involves free radical ends which of course do not associate and which interact only weakly with solvents. Consequently, the early investigators assumed that the course of propagation of radical polymerization is independent of the environment (see, for example, the recent monograph by Walling60). Actually, more recent studies, notably by Russell,36 showed that the nature of the solvent sometimes might considerably affect even the course of radical reactions. Therefore, unusual behavior of the propagation step might be expected in certain solvents. 

Most radicals are transient species. They (e.%. 1-10) decay by self-reaction with rates at or close to the diffusion-controlled limit (Section 1.4). This situation also pertains in conventional radical polymerization. Certain radicals, however, have thermodynamic stability, kinetic stability (persistence) or both that is conferred by appropriate substitution. Some well-known examples of stable radicals are diphenylpicrylhydrazyl (DPPH), nitroxides such as 2,2,6,6-tetramethylpiperidin-A -oxyl (TEMPO), triphenylniethyl radical (13) and galvinoxyl (14). Some examples of carbon-centered radicals which are persistent but which do not have intrinsic thermodynamic stability are shown in Section 1.4.3.2. These radicals (DPPH, TEMPO, 13, 14) are comparatively stable in isolation as solids or in solution and either do not react or react very slowly with compounds usually thought of as substrates for radical reactions. They may, nonetheless, react with less stable radicals at close to diffusion controlled rates. In polymer synthesis these species find use as inhibitors (to stabilize monomers against polymerization or to quench radical reactions - Section 5,3.1) and as reversible termination agents (in living radical polymerization - Section 9.3). 

The hydrogen abstraction addition ratio is generally greater in reactions of heteroatom-centered radicals than it is with carbon-centered radicals. One factor is the relative strengths of the bonds being formed and broken in the two reactions (Table 1.6). The difference in exothermicity (A) between abstraction and addition reactions is much greater for heteroatom-centered radicals than it is for carbon-centered radicals. For example, for an alkoxy as opposed to an alkyl radical, abstraction is favored over addition by ca 30 kJ mol"1. The extent to which this is reflected in the rates of addition and abstraction will, however, depend on the particular substrate and the other influences discussed above. 

Hydroxy radical and sulfate radical anion, though they may sometimes give rise to similar products, show quite different selectivity in their reactions with unsaturated substrates. In particular, the sulfate radical anion has a somewhat lower propensity for hydrogen abstraction than the hydroxyl radical. For example, the sulfate radical anion shows little tendency to abstract hydrogen from mcthacrylic acid.232... 

Stable radicals can show selectivity for particular radicals. For example, nitroxides do not trap oxygcn-ecntcrcd radicals yet react with carbon-ccntcrcd radicals by coupling at or near diffusion controlled rates.179,184 This capability was utilized by Rizzardo and Solomon181 to develop a technique for characterizing radical reactions and has been extensively used in the examination of initiation of radical polymerization (Section 3.5.2.4). In contrast DPPH, w hile an efficient... 

To avoid these stability problems, it is necessary to minimize the proportion of chains that terminate by radical-radical reaction. One way of achieving this is to conduct the polymerization in the presence of an appropriate chain transfer agent. For example, if polymerization is performed in the presence of a H-donor chain transfer agent, conditions can be chosen such that most chains terminate by hydrogen-atom transfer. Bagby et al.iA examined the thermal stability of PMMA formed with dodecanethiol. These polymer chains will then possess, more... 

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