A-hydroxyalkyl radical

Ceric ions react rapidly with 1,2-diols. There is evidence for chelation of cerium and these complexes are likely intermediates in radical generation10 106 The overall chemistry may be understood in terms of an intermediate alkoxy radical which undergoes p-scission to give a carbonyl compound and a hydroxyalkyl radical (Scheme 3.59). However, it is also possible that there is concerted electron transfer and bond-cleavage. There is little direct data on the chemical nature of the radical in termediates. 

The reaction fails if the decarboxylation produces a radical that is easily oxidized, such as an a-hydroxyalkyl radical.2 In intermediate cases, such as tert-alkyl or a-alkoxyalkyl radicals,2 the yield based on the parent quinono is usually improved by using an excess of persulfate and carboxylic acid to compensate for the loss of radicals due to oxidation (footnote b, Table I). 

A biomimetic oxidation with perfluorinated porphyrin complexes [(F20TPP) FeCl] showed high catalytic activity with secondary alcohols with over 97% yield in all cases [144]. Furthermore, this catalyst is able to oxidize a broad range of alcohols under mild conditions with wCPBA as terminal oxidant. Here, an a-hydroxyalkyl radical species is proposed as central intermediate. 

Even though the radical attacking ethyl alcohol in the above reaction generated a-hydroxyethyl rather then ethoxy free radical, there seems to be little or no tendency for alkoxy free radicals to rearrange to a-hydroxyalkyl radicals. Thus in the reaction... 

From the above it is clear that DMPO can undergo the addition-oxidation mechanism with water as the nucleophile, provided a suitable oxidant is present. With a primary alcohol competing, the O-connected alkoxy spin adduct is formed in addition to HO-DMPO". On the other hand, with a hydroxyl radical source a competing alcohol will undergo hydrogen abstraction by HO" and form an a-hydroxyalkyl radical which forms a C-connected spin adduct. This criterion clearly can distinguish between the two mechanisms at least in model systems (for recent examples, see Reszka and Chignell, 1995 Janzen et al., 1995 Thomas et al., 1996). 

Oxidation of alcohols with a variety of oxidizing agents leads to a-hydroxyalkyl radicals. These attack protonated heteroaromatic bases only when obtained from methanol or primary alcohols, with secondary alcohols no attack takes place, probably owing to the ease with which such a-hydroxyalkyl radicals are oxidized. (This limitation does not apply to radiation-induced oxyalkylation, see later.)... 

The results indicate that C-6 in purine and 2-aminopurine (17) is more reactive than C-8 or C-2, while the primary attack at C-8 in adenine and 6-ethoxypurine (18) indicates that C-8 is more reactive than C-2. The order of reactivity toward a-hydroxyalkyl radicals in the purine system is therefore C-6 > C-8 > C-2. 

Similar hypervalent iodine radicals (9-1-2) are formed in the reaction of alkyl radicals with alkyliodides (R + RI — R2I ), and as an intramolecular complex they are stable enough that a reaction with 02 is only low (Miranda et al. 2000). Such 9-X-2 radicals have also been postulated as intermediates in the reduction of alkylhalides by a-hydroxyalkyl radicals (Lemmes and von Sonntag 1982). 

In the case of a-hydroxyalkyl radicals, the corresponding carbonyl compounds are formed in full yields. In contrast, the oxidation of a-alkoxyalkyl radicals by Fe(CN)63 may not always be a straightforward outer-sphere ET reaction (Janik et al. 2000a,b). Details are as yet not fully understood. 

Although a-hydroxyalkyl radicals such as the hydroxymethyl radical are oxidized without an adduct being noticed [reaction (14) k= 1.6 x 108 dm3 mol1 s 1], such a complex becomes apparent in the case of P-hydroxyalkyl radicals [reactions (15) and (16) k15 = 3 x 107 dm3 mol1 s k16 = 330 s Freiberg and Meyer-stein 1980], whereby the epoxide is formed (Soylemez and von Sonntag 1980). 

Although a-hydroxyalkyl radicals are good reducing agents their reduction po-... 

These reactions are real tautomerization reactions, but the quite common water elimination reactions can also completely change the redox property of a radical. A case in point is the radical derived from ethylene glycol which is a reducing a-hydroxyalkyl radical which is transformed by water elimination into the fomylmethyl radical (see below) whose oxidizing property has been discussed above [reaction (20)]. Similarly, the phenol OH-adduct is a reason-... 

This addition reaction is not restricted to a-hydroxyalkyl radicals, although this type of radical has been most widely investigated. Thus, allylic radical derived from 5MeCyt (Zhang and Wang 2003) and radicals derived from amino acids (Elad and Rosenthal 1969) are also reported to undergo this reaction. In DNA, they play a role in the formation of tandem lesions (Chap. 12.5), and it is likely that this kind of reaction contributes to free-radical-induced DNA/DNA and DNA/protein cross-linking. 

Akhlaq MS, Murthy CP, Steenken S, von Sonntag C (1989) The reaction of a-hydroxyalkyl radicals and their anions with oxidized dithiothreitol. A pulse radiolysis and product analysis study. J Phys Chem 93 4331-4334... 

AravindakumarCT, Mohan FI.MudaliarM, RaoBSM, Mittal JP, Schuchmann MN, von Sonntag C (1994) Addition of eaq and FI atoms to hypoxanthine and inosineand the reactions of a-hydroxyalkyl radicals with purines. A pulse radiolysis and product study. Int J Radiat Biol 66 351-365... 

Behrens G, Koltzenburg G (1985) Elimination of ammonium ion from a-hydroxyalkyl radicals of serine and threonine in aqueous solution and the difference in the reaction mechanism. Z Natur-... 

Lemmes R, von Sonntag C (1982) On the formation of deoxy sugars from halogenated carbohydrates by a-hydroxyalkyl radicals considerations for the optimisation of reaction conditions. Carbohydr Res 105 276-282... 

Schuchmann MN, von Sonntag C (1982) Flydroxyl radical induced oxidation of diethyl ether in oxygenated aqueous solution. A product and pulse radiolysis study. J Phys Chem 86 1995-2000 Schuchmann MN, Schuchmann H-P, Knolle W, von Sonntag J, Naumov S, Wang W-F, von Sonntag C (2000) Free-radical chemistry of thiourea in aqueous solution, induced by OFI radical, FI atom, a-hydroxyalkyl radicals, photoexcited maleimide, and the solvated electron. Nukleonika 45 55-62... 

Because of the rapid 1,2-H-shift [reaction (51)] and the ready conversion of the ensuing a-hydroxyalkyl radical into H02702 by 02 [cf. reactions (8) and (10)/(11)], primary and secondary peroxyl are often the precursor of 02 in theses systems. Furthermore, the P-fragmentation reaction (60) creates a new radical and hence a new peroxyl radical, a situation which makes the elucidation of mechanistic details often very difficult if not impossible. The peroxyl radical systems that have been investigated in detail thus far have been discussed by von Sonntag and Schuchmann (1997). 

The other functional groups, especially the second carbonyl function, withdraws considerable electron density, and hence the pK3 values of these O-pro-tonated radical anions are much lower than those of the simple a-hydroxyalkyl radicals (Thy pKa = 6.9 (Hayon 1969) Ura pfCa = 7.2 (Shragge and Hunt 1974) the value of 4.3 reported for the pfCa for the protonated 5,6Me2Ura radical anion (Aravindakumar et al. 1998) is surprising low and difficult to explain on the basis of the effects of methyl substituents on the pfCa values of a-hydroxyalkyl radi-... 

In dCyd, the a-hydroxyalkyl radical formed upon -OH attack at the 5 -posi-tion must add to C(6) [reaction (195)] that fast that it is not scavenged effectively by 02. An oxidation of the ensuing C(5) radical by 02 and deamination are further likely steps [reaction (196)] to the observed product (Wagner et al. 1999 for its yield see Table 10.16). 

Table10.23. Rateof reaction (unit dm3 mol 1 s ) of a-hydroxyalkyl radicals with purines. (Aravindakumar et al. 1994) ...

Ito T, Shinohara H, Hatta H, Nishimoto S-l (1999) Radiation-induced and photosensitized splitting of C5-C5 -linked dihydrothymine dimers product and laser flash photolysis studies on the oxidative splitting mechanism. J Phys Chem A 103 8413-8420 ItoT, Shinohara H, Hatta H, Fujita S-l, Nishimoto S-l (2000) Radiation-induced and photosensitized splitting of C5-C5 -linked dihydrothymine dimers. 2. Conformational effects on the reductive splitting mechanism. J Phys Chem A 104 2886-2893 ItoT, Shinohara H, Hatta H, Nishimoto S-l (2002) Stereoisomeric C5-C5 -linked dehydrothymine dimers produced by radiolytic one-electron reduction of thymine derivatives in anoxic solution structural characteristics in reference to cyclobutane photodimers. J Org Chem 64 5100-5108 Jagannadham V, Steenken S (1984) One-electron reduction of nitrobenzenes by a-hydroxyalkyl radicals via addition/elimination. An example of an organic inner-sphere electron-transfer reaction. J Am Chem Soc 106 6542-6551... 

---