Radical intermediates detection

Distinction between PL and ET mechanisms is not straightforward. Various experimental methods have been used so far to demonstrate the ET process, including spectroscopic detection of radical intermediates detection of products indicative of radical intermediates " and measurement of secondary deuterium " and carbonyl carbon kinetic isotope effects (KlEs) "" . The combination of several experimental methods, including KIE, substituent effect and probe experiments, was shown to be useful in distinguishing the ET process from the PL process for the addition reactions of the Grignard and other organometallic reagents . 

EPR spectra have been widely used in the study of reactions to detect fiee-radical intermediates. An interesting example involves the cyclopropylmethyl radical. Much chemical experience has indicated that this radical is unstable, giving rise to 3-butenyl radical rapidly after being generated. 

It is important to emphasize that direet studies sueh as those earned out on the eyelopropylmethyl radieal ean be done with low steady-state eoneentrations of the radical. In the case of the study of the eyelopropylmethyl radical, removal of the source of irradiation leads to rapid disappearance of the EPR spectrum, because the radicals react rapidly and are not replaced by continuing radical formation. Under many conditions, the steady-state concentration of a radical intermediate may be too low to permit direct detection. Failure to observe an EPR signal, therefore, cannot be taken as conclusive evidence against a radical intermediate. 

One aspect of both EPR and CIDNP studies that should be kept in mind is that either is capable of detecting very small amounts of radical intermediates. This sensitivity makes both techniques quite useful, but it can also present a pitfall. The most prominent features of either EPR or CIDNP spectra may actually be due to radicals that account for only minor amounts of the total reaction process. An example of this was found in a study of the decomposition of trichloroacetyl peroxide in alkenes. 

Kattenberg and coworkers54 studied the chlorination of a-lithiated sulfones with hexachloroethane. These compounds may react as nucleophiles in a nucleophilic substitution on halogen (path a, Scheme 5) or in an electron transfer reaction (path b, Scheme 5) leading to the radical anions. The absence of proof for radical intermediates (in particular, no sulfone dimers detected) is interpreted by these authors in favour of a SN substitution on X. 

The very fast oxidation of the radical precludes its detection and identification by esr however, reacting mixtures are capable of initiating polymerisation of acrylonitrile. The oxidations of allylic alcohols by V(V) perchlorate are ca. thirty times faster than those of saturated alcohols. This is supporting evidence for radical intermediates in view of the expected delocalisation of the free electron... 

This is an example of a reversible reaction the standard electrode potential of the 2PS/PSSP + 2c couple is zero at pH 7. The oxidation kinetics are simple second-order and the presence of a radical intermediate (presumably PS-) was detected. Reaction occurs in the pH range 5 to 13 with a maximum rate at pH 6.2, and the activation energy above 22 °C is zero. The ionic strength dependence of 2 afforded a value for z Zg of 9 from the Bronsted relation... 

ESR experiments employing in situ photolytic decomposition of the peroxydisulfate anion (S20g ) have been carried out to study the reaction of S04 with aliphatic sulfoxides. In the case of dimethyl sulfoxide three radicals are detected ( CHj, CH3 S02, CH2 S(0)CH3), the proportion being pH-dependent. The reaction is assumed to proceed via an initially formed radical cation (not detected) which would be rapidly hydrated to give an intermediate identical with that generated by OH addition on the sulfoxide. Such a process parallels the rapid hydration of radical cations formed from thiophene in their reactions with SO/ and... 

Organic peroxides such as cumene hydroperoxide and t-butyl hydroperoxide have extensively been used as experimental agents. They provoke lipid peroxidation in hepatocytes, probably by the generation of alkoxyl and peroxyl radical intermediates after reaction with cytochrome P450. Other cytotoxic mechanisms are probably involved including protein thiol and non-protein thiol oxidation and deranged calcium homeostasis (Jewell et al., 1986). In fact, the addition of cumene hydroperoxide to isolated bUe duct cells, devoid of cytochrome P450 activity, still results in cell death but lipid peroxidation is not detectable (Parola et al., 1990). 

Evidence in support of radical intermediates with MMO from both M. capsulatus (Bath) and M. trichosporium 0B3b was reported from experiments in which substrate radicals were trapped during turnover (89, 90). The amount of trapped radical, however, was not quantified in these experiments. In other reports, no diffusable radical species were detected in reactions with MMO from M. trichosporium 0B3b (61). 

Quite apart from such specific physical methods for the detection of radicals, it should be emphasised that more general indications that radical intermediates are involved in a particular reaction are provided by its high susceptibility to the addition of radical initiators (cf. p. 314) or inhibitors (cf. p. 300), and (compared with polar reactions) its relative insusceptibility to change of solvent. 

Ionomer membranes are used in fuel cells in order to separate the anode and cathode compartment and to allow the transport of protons from the anode to the cathode. The typical membrane is Nation , which consists of a perfluorinated backbone and side chains terminated by sulfonic groups. In the oxidizing environment of fuel cells, Nation , as well as other membranes, is attacked by reactive oxygen radicals, which reduce the membrane stability. Direct ESR was used recently in our laboratory to detect and identify oxygen radicals as well as radical intermediates formed in perfluorinated membranes upon exposure to oxygen radicals [73,74]. The three methods used to produce oxygen radicals in the laboratory and the corresponding main reactions are shown below. 

Recently the two-step decomposition of azomethane was proved in the study of the femtosecond dynamics of this reaction [68]. The intermediate CH3N2 radical was detected and isolated in time. The reaction was found to occur via the occurrence of the first and the second C—N bond breakages. The lifetime of CH3N2 radical is very short, i.e., 70fsec. The quantum-chemical calculations of cis- and /nmv-azomcthanc dissociation was performed [69]. 

The intermediate formation of the nitroxyl radical was detected in the oxidation of 2-propanol retarded by diphenylamine chain termination occurs by cyclic mechanisms involving both... 

ESR and CIDNP studies intended to detect the radical intermediates failed [63], Conjugate addition of a vinylcuprate reagent to an enone takes place with retention of the vinyl geometry indicating that no vinyl radical intermediate is involved [64, 65], Kinetic isotope effects and substituent effects in cuprate addition to benzophenone indicate that C-C bond formation is rate-determining, which is not consistent with the involvement of a radical ion pair intermediate [66]. 

When applied to electron-transfer reactions, this kinetic isotope effect technique can provide information on the real reaction pathway leading to the formation of the product. Frequently, spectroscopic detection of species or identification of products is indicative of radical intermediates. The formation of the intermediates could simply be a blind step. 

In the preceding eqnation, the primary anion-radical gives the l-chloro-2,2,2-trifluoroethyl radical. In vivo, this radical was detected by the spin-trapping method (Poyer et al. 1981). Ahr et al. (1982) had presented additional evidence for the formation of the radical as an intermediate in halo-thane metabolism and identified l-chloro-2,2-difluoroethene as a product of radical stabilization. Metabolytic transformations of l-chloro-2,2-difluoroethene lead to acyl halides, which are relevant to halothane biotoxicity (Guengerich and Macdonald 1993). 

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