Free radical transition states

Organic reactions can be loosely grouped into three classes depending on the character of the activated complex through which these reactions can proceed dipolar, isopolar, and free-radical transition-state reactions [15, 468]. 

Free-radical activated complexes are formed by the creation of unpaired electrons during homolytic bond cleavage. Free-radical transition-state reactions with small or negligible solvent effects are found among radical-pair formation and atom-transfer reactions such as ... 

Solvent Effects on Free-Radical Transition State Reactions... 

Azo compounds can exist in either the cis or trans form. It is reasonable to assume that the azoalkanes in Table 5-8 exhibit the trans configuration. Contrary to the small solvent effects obtained in the decomposition of trans -azoalkanes, the thermolysis of definite cu-azoalkanes reveals a significant solvent influence on rate. Thermolysis of ah-phatic symmetrical cw-tert-azoalkanes can lead either to the corresponding trans-tert-azoalkanes, presumably via an inversion mechanism, or to tert-alkyl radicals and nitrogen by decomposition via a free-radical transition state [192]. An example of the first type of reaction is the Z)I E) isomerization of [1,1 jazonorbornane. Its rate is virtually solvent-independent, which is consistent with a simple inversion mechanism [565, 566], The second reaction type is represented by the thermal decomposition of cis-2,2 -dimethyl-[2,2 ]azopropane, for which a substantial decrease in rate with increasing solvent polarity has been found [193] cf Eq. (5-60). 

Mankind has used metals for milletmia, but the relation between metals and cancer has only been known for over a century. Only in the past tlnee decades have the tools been available to analyze the molecular and cellular effects of metals on cancer, and only very recently has it been possible to examine the role of free radicals in normal and disease states. Because of their ability to produce free radicals, transition metals provide a nnique means by which to study not only metal-related diseases, but the effects of free radicals on DNA damage, intracellular signaling, and cell-to-cell coimnunication. With the completion of the human genome project and the use of novel technologies snch as genomics and proteomics, it will soon be possible to examine the global effects of free radicals on genes and their expression. 

Since the bond is broken symmetrically and results in free radicals, the process is called either a radical or a homolytic reaction. The rate of a homolytic reaction is highly dependent on the stabilities of the radicals, and substituent constants for homolytic reactions should therefore take into account the effects of substitution on the resonance stabilisation of the radical transition state. It is therefore not surprising that Hammett a constants have enjoyed very little success in predicting the rates of radical reactions. 

Free-radical reactivity of thiazole has been calculated by semiempirical methods, and results free valence and localization energy) have been compared with experimental data. For mono- and dimethylthiazoles the radical localization energy of the unsubstituted position may be correlated with the logarithm of experimental reactivity (180, 200). The value of the slope shows that a Wheland-type complex is involved in the transition state. 

This behavior stems from the greater stability of secondary compared with primary free radicals The transition state for the step m which a chlorine atom abstracts a hydro gen from carbon has free radical character at carbon... 

Free-radical reaction rates of maleic anhydride and its derivatives depend on polar and steric factors. Substituents added to maleic anhydride that decrease planarity of the transition state decrease the reaction rate. The reactivity decreases in the order maleic anhydride > fumarate ester > maleate ester. 

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. 

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. ... 

Why do free-radical reactions involving neutral reactants and intermediates respond to substituent changes that modify electron distribution One explanation has been based on the idea that there would be some polar character in the transition state because of the electronegativity differences of the reacting atoms ... 

In a free radical, there is a third electron in the system. It cannot occupy the same orbital as the other two electrons and must instead be in an antibonding level. As a result, the transition state for migration is much less favorable than for the corresponding carboca-tion. 

Most of the free-radical mechanisms discussed thus far have involved some combination of homolytic bond dissociation, atom abstraction, and addition steps. In this section, we will discuss reactions that include discrete electron-transfer steps. Addition to or removal of one electron fi om a diamagnetic organic molecule generates a radical. Organic reactions that involve electron-transfer steps are often mediated by transition-metal ions. Many transition-metal ions have two or more relatively stable oxidation states differing by one electron. Transition-metal ions therefore firequently participate in electron-transfer processes. 

A number of metal chelates containing transition metals in their higher oxidation states are known to decompose by one electron transfer process to generate free radical species, which may initiate graft copolymerization reactions. Different transition metals, such as Zn, Fe, V, Co, Cr, Al, etc., have been used in the preparation of metal acetyl acetonates and other diketonates. Several studies demonstrated earlier that metal acetyl acetonates can be used as initiators for vinyl polymeriza-... 

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