Radical Hydroxylation Addition-Elimination

SCHEME 14.3 Radical hydroxylation of benzene with HO radical (Adapted from Ref. [28]). 

In addition, both I and the radical cation can trap O, leading to new radical species and complication of the overall mechanistic picture [29]. In case of alkylaromatics, radical cations unda-go side-chain fragmentation to benzyl radicals, giving rise to side-chain oxidation products [15, 28] (see Section 14.2.4). 

Hydroxyl radicals possess week electrophilic properties as indicated by the order of reactivity of substituted benzenes and distribution of phenolic isomers, although the latter depends on the reaction conditions [28, 29]. The Fenton hydroxylation in aqueous solution reveals small ( 5%) values of the NIH shift (i.e., migration of hydrogen atom from the site of hydroxylation to the adjacent carbon [30]). The reaction in CH CN demonstrated remarkably high shift values (30-40%) [31], which is typical of enzymatic processes [30]. Sawyer and coworkers proposed that the change in solvent might favor a mechanistic shift from HO to a metal-centered oxidant [32]. 

---

D. Reaction of Phenols with Hydroxyl Radicals. The Addition/Elimination... 

The addition/elimination mechanism (equation 11) for formation of phenoxyl radicals by OH reaction with phenols is now documented for a vast number of substituted phenols , catechols , resorcinol , hydroquinones and hydroxylated heterocyclics . The addition/elimination mechanism is also operative in OH reactions with anilines to yield the nitrogen-centered anilinyl radicals (equation i2) 408-in... 

A distinctly different reaction cascade leading to tetrahydrofurans is illustrated in Scheme 40 [74]. It was proposed that these reactions proceed by iodine-mediated deoxygenation of the peroxyl radical to an alkoxyl radical, which undergoes intramolecular C-H abstraction to form a y9-keto radical [74], Elimination of an a-hydrogen atom generates an enone, which is ultimately captured intramolecularly by conjugate hydroxyl addition to give a tetrahydrofuran (Scheme 40). 

Radical addition-elimination mechanism with participation of an electrophilic V(IV)-00 species was proposed for aromatic hydroxylation by a peroxo complex [V0(02)(pic)(Hj0)2] (pic=picolinate) that oxidizes benzene at room temperature in CH CN to produce phenol in a yield of 55%, without any coupling products (Scheme 14.4) [33]. A radical anion was suggested as an alternative hydroxylating species [34]. 

Chromanoxylium cation 4 preferably adds nucleophiles in 8a-position producing 8a-substituted tocopherones 6, similar in structure to those obtained by radical recombination between C-8a of chromanoxyl 2 and coreacting radicals (Fig. 6.4). Addition of a hydroxyl ion to 4, for instance, results in a 8a-hydroxy-tocopherone, which in a subsequent step gives the /zara-tocopherylquinone (7), the main (and in most cases, the only) product of two-electron oxidation of tocopherol in aqueous media. A second interesting reaction of chromanoxylium cation 4 is the loss of aproton at C-5a, producing the o-QM 3. This reaction is mostly carried out starting from tocopherones 6 or /zora-tocopherylquinone (7) under acidic catalysis, so that chromanoxylium 4 is produced in the first step, followed by proton elimination from C-5a. In the overall reaction of a tocopherone 6, a [ 1,4] -elimination has occurred. The central species in the oxidation chemistry of a-tocopherol is the o-QM 3, which is discussed in detail subsequently. 

Adults require 1-2 mg of copper per day, and eliminate excess copper in bile and feces. Most plasma copper is present in ceruloplasmin. In Wilson s disease, the diminished availability of ceruloplasmin interferes with the function of enzymes that rely on ceruloplasmin as a copper donor (e.g. cytochrome oxidase, tyrosinase and superoxide dismutase). In addition, loss of copper-binding capacity in the serum leads to copper deposition in liver, brain and other organs, resulting in tissue damage. The mechanisms of toxicity are not fully understood, but may involve the formation of hydroxyl radicals via the Fenton reaction, which, in turn initiates a cascade of cellular cytotoxic events, including mitochondrial dysfunction, lipid peroxidation, disruption of calcium ion homeostasis, and cell death. 

The simple phenol system has been discussed here at some length, because material balance is obtained and mechanistic details are fairly well understood. However, according to the data in Tables 3.5 and 3.6, there is a very noticeable gap in the material balance in the case of the hydroxylated benzoic acids, although some aspects such as the acid-catalyzed water elimination, in salicylate also more pronounced in the case of the para-OH-adduct radical, are very similar (Mark and von Sonntag, unpubl.). Interestingly, addition of Fe(III) to oxidize the intermediates also did not improve the material balance (Tables 3.5 and 3.6). From this, it follows that the underlying chemistry of the salicylate and the other hydroxybenzoate systems are at present not yet adequately understood, and the... 

J. Llano et al., Mechanism of hydroxyl radical addition to imidazole and subsequent water elimination. J. Phys. Chem. B 103, 5598-5607 (1999)... 

In addition, the hydrated electron acts as a nucleophile, especially with organic molecules that contain halogen atoms (Eq. 6-16). This reaction results in rapid elimination of a halide ion from the initially formed negatively charged organic species. The reaction of Eq. 6-16 is of special interest for the degradation of per-halogenated saturated hydrocarbons that are usually not affected by hydroxyl radicals (Sun et al, 2000). 

The peroxyl radicals M-0-0 thus formed undergo a variety of molecular rearrangements and/or elimination reactions until the final oxidation products are formed. In reality, these oxidation products are interfering with hydroxyl radical attack on M and hence they are complicating the product spectrum considerably. Additionally, the bicarbonate and carbonate radicals may introduce selective oxidation reactions into the degradation cycle (Fig. 6-16). 

Taylor et al. [104] investigated the reaction of hydroxyl radicals with acetaldehyde in a wide temperature range using a quantum RRK model to describe the competition between addition and abstraction. They conclude that different reaction mechanisms occur, depending on the temperature, and that OH addition followed by CH3 elimination is the dominant reaction pathway between 295 and 600 K. Moreover, they claimed that the H-atom elimination pathway is largely insignificant, except possibly at the lowest temperatures. 

---