Chain sequence peroxidation

The peroxides and peracids formed in autocatalytic systems are highly energetic molecules. We now see that the Co/Mn/Br catalyst serves to rapidly relax this energy in increasingly lower steps winding up with a highly selective bromide(O) radical (probably as a complex with the metal). The bromide(O) transient species quickly reacts with methylaromatic compounds to form PhCHj radicals and hence continues to propagate the chain sequence. 

Oxygen is omnipresent in our environment and the deterioration of rubbers and plastics by peroxidation is the normal cause of property deterioration in most polymers under ambient conditions. Peroxidation is a free radical chain reaction, shown in summary in reactions 3.1 and 3.2. Under normal conditions it is initiated by hydroperoxides that are formed in each cycle of the peroxidation chain sequence (reaction 3.1). Hydroperoxides are very unstable compounds due to the weakness of the peroxide bond which readily undergoes thermolysis when heated (reaction 3.3). This reaction is powerfully catalysed by transition metal ions. 

The i-butoxy radical itself can abstract a-hydrogens directly. This is evident from studies with di-i-butyl peroxide, which decomposes homolytically at temperatures above 125°c ((i-Bu)2022 i-BuO ), Primary and secondary alkylamines react to form imines . The mechanism has been viewed as a radical chain sequence following abstraction of the a-hydrogen (Scheme 35). Tertiary alkylamines... 

The peroxidation chain sequence (3) and (4) continues as long as oxygen is present in the system. 

A thermal acylation via a radical chain sequence was achieved for chloranil (38) and benzaldehyde (similar to Scheme 11) at elevated temperatures using benzoyl peroxide as a radical initiator. As an example, the monoester 39 was readily obtained in yields of 75 to 80% at 120°C. Thus, Schenck concluded that a free radical chain mechanism during photolysis should occur solely at higher temperatures. ° ... 

Similar hydroxylation-oxidations can be carried out using a catalytic amount of osmium tetroxide with A-methylmorpholine oxide-hydrogen peroxide or phenyliodosoacetate." A recent patent describes the use of triethylamine oxide peroxide and osmium tetroxide for the same sequence. Since these reactions are of great importance for the preparation of the di-hydroxyacetone side-chain of corticoids, they will be discussed in a later section. 

Radical X , which initiates the reaction, is regenerated in a chain propagation sequence that, at the same time, produces an organic peroxide. The latter can be cleaved to form two additional radicals, which can also react with the unsaturated fatty acids to set up the autocatalytic process. Isomerization, chain cleavages, and radical coupling reactions also occur, especially with polyunsaturated fatty acids. For example, reactive unsaturated aldehydes can be formed (Eq. 21-14). 

The reaction has a radical-chain mechanism and the chains can be initiated by light or by chemicals, usually peroxides, ROOR. Chemical initiation requires an initiator with a weak bond that dissociates at temperatures between 40-80°. Peroxides are good examples. The 0-0 bond is very weak (30-50 kcal) and on heating dissociates to alkoxyl radicals, RO-, which are reactive enough to generate the chain-propagating radicals from the reactants. The exact sequence... 

The sulfur atom of methionine residues may be modified by formation of sulfonium salts or by oxidation to sulfoxides or the sulfone. The cyanosulfonium salt is not particularly useful for chemical modification studies because of the tendency for cyclization and chain cleavage (129). This fact, of course, makes it very useful in sequence work. Normally, the methionine residues of RNase can only be modified after denaturation of the protein, i.e., in acid pH, urea, detergents, etc. On treatment with iodoacetate or hydrogen peroxide, derivatives with more than one sulfonium or sulfoxide group did not form active enzymes on removal of the denaturing agent (130) [see, however, Jori et al. (131)]. There was an indication of some active monosubstituted derivatives (130, 132). 

It was also described that some common vinyl polymers, such as polymethyl methacrylate prepared with benzoyl peroxide, are able to initiate a further polymerization if heated in the presence of a second monomer [158). These phenomena must be interpreted by the existence of peroxide links inside the polymethyl methacrylate chain [229). Indeed any activity is destroyed on prolonged heating and this polymer can be used for initiating the polymerization of styrene. However the relative length of the sequences and the molecular weight of the product before and after copolymerization have not yet been determined. 

A simple example involves the reaction of the silyl ether 213, made from the corresponding 4-hydroxy-alkene by treatment with (bromomethyl)chloro-dimethylsilane, with tributyltin hydride and a radical initiator. Bromine abstraction and intramolecular cyclization with the double bond leads to the bicyclic 214, which upon oxidation with hydrogen peroxide gives the branched-chain 215 in an overall yield of 73% from the alcohol precursor of 213 (Scheme 21). When the sequence is conducted with the C-4 epimeric starting alcohol, the final product again has the hydroxymethyl group cis-related to the hydroxy group.217... 

Well-defined peptides of known sequence have been used to shed light on the mechanism of catalysis in the epoxidation of enones with hydrogen peroxide [91, 93-95]. The peptide sequences of the catalysts have been systematically varied and correlated with catalytic activity and selectivity. From the many variations investigated it was concluded (i) that the N-terminal region of the peptides harbors the catalytically active site, and that (ii) a helical conformation is required for the peptide catalysts to be active. The latter conclusion is supported both by the dependence of catalytic activity on chain-length and by IR investigations [91, 94]. NMR data that might aid further elucidation of catalyst structure, interaction with the substrate enones, etc., are, unfortunately, not yet available. 

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