Radical reactions involving ring substituents

Treatment of 2-methylthiirane with t-butyl hydroperoxide at 150 °C in a sealed vessel gave very low yields of allyl disulfide, 2-propenethiol and thioacetone. The allyl derivatives may be derived from abstraction of a hydrogen atom from the methyl group followed by ring opening to the allylthio radical. Percarbonate derivatives of 2-hydroxymethylthiirane decompose via a free radical pathway to tar. Acrylate esters of 2-hydroxymethylthiirane undergo free radical polymerization through the double bond. 

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Toluene, an aLkylben2ene, has the chemistry typical of each example of this type of compound. However, the typical aromatic ring or alkene reactions are affected by the presence of the other group as a substituent. Except for hydrogenation and oxidation, the most important reactions involve either electrophilic substitution in the aromatic ring or free-radical substitution on the methyl group. Addition reactions to the double bonds of the ring and disproportionation of two toluene molecules to yield one molecule of benzene and one molecule of xylene also occur. 

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 dehydrodimerization reaction involving aromatic radical-cations is fast only when electron donating substituents are present in the benzene ring. These substituents stabilise the a-intermediate. Benzene, naphthalene and anthracene radical-cations form a a-sandwich complex with the substrate but lack the ability to stabilise the a-intermediate so that radical-cation substrate reactions are not observed. The energy level diagram of Scheme 6.4 illustrates the influence of electron donating substituents in stabilising the Wheland type a-intermediate. 

The intrinsic stability of the aromatic n system has two major consequences for the course of reactions involving it directly. First, the aromatic ring is less susceptible to electrophilic, nucleophilic, and free-radical attack compared to molecules containing acyclic conjugated n systems. Thus, reaction conditions are usually more severe than would normally be required for parallel reactions of simple olefins. Second, there is a propensity to eject a substituent from the tetrahedral center of the intermediate in such a way as to reestablish the neutral (An + 2)-electron system. Thus, the reaction is two step, an endothermic first step resulting in a four-coordinate carbon atom and an exothermic second step, mechanistically the reverse of the first, in which a group is ejected. The dominant course is therefore a substitution reaction rather than an addition. 

This chapter begins with an introduction to the basic principles that are required to apply radical reactions in synthesis, with references to more detailed treatments. After a discussion of the effect of substituents on the rates of radical addition reactions, a new method to notate radical reactions in retrosynthetic analysis will be introduced. A summary of synthetically useful radical addition reactions will then follow. Emphasis will be placed on how the selection of an available method, either chain or non-chain, may affect the outcome of an addition reaction. The addition reactions of carbon radicals to multiple bonds and aromatic rings will be the major focus of the presentation, with a shorter section on the addition reactions of heteroatom-centered radicals. Intramolecular addition reactions, that is radical cyclizations, will be covered in the following chapter with a similar organizational pattern. This second chapter will also cover the use of sequential radical reactions. Reactions of diradicals (and related reactive intermediates) will not be discussed in either chapter. Photochemical [2 + 2] cycloadditions are covered in Volume 5, Chapter 3.1 and diyl cycloadditions are covered in Volume 5, Chapter 3.1. Related functional group transformations of radicals (that do not involve ir-bond additions) are treated in Volume 8, Chapter 4.2. 

NaX (13X) zeolite is the catalyst of choice for benzylic chlorinations while zeolites with high Bronsted acidity (ZF520) affected ring chlorination, even though X-ray diffraction studies have later shown that the zeolite lattice collapses under the reaction conditions127. In both instances the mechanism involves active site outside the channel network of the microporous solid. Contradictory to the latter authors, Delude and Laszlo suggest that aluminum-rich zeolites would preferably initiate radical chain reaction via formation of siloxy radicals. Both the reaction medium and substituents on the aromatic substrate have a profound effect on the rate and selectivity of these reactions. Interestingly, the catalyst applied in the radical chlorinations can be easily recycled and reused. The opposite has been observed in the ionic chlorinations where the catalyst has rapidly lost its activity. 

The aromatic-OH radical reaction proceeds via two pathways (a) a minor one (of order 10%) involving H-atom abstraction from C—H bonds of, for benzene, the aromatic ring, or for alkyl-substituted aromatic hydrocarbons, the alkyl-substituent groups and (b) a major reaction pathway (of order 90%) involving OH radical addition to the aromatic ring. For example, for toluene these reaction pathways are ... 

Another kind of tandem cyclization was observed when 1-benzoyl indoles with 3-EW substituents reacted with dimethyl malonate and Mn(0Ac)j. Tetracyclic products are obtained in good yield. <94TL1283> It is presumed that the reaction involves initial attack by the b/s-carbomethoxymethyl radical on the indole ring at C2, followed by a second oxidation and cyclization. 

Halogenations of quinoline, isoquinoline, acridine, and phenanthridine will be discussed here. Reaction usually occurs in a homocyclic fused ring rather than in the 7r-deficient pyridine moiety, especially in acidic media. Relatively mild conditions suffice, but under more vigorous regimes radical involvement can result in heteroring halogenation. Substituents are able to modify reactivity and regiochemistry. 

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