Hydroxymethyl radicals, reaction

Simple alkyl radicals such as methyl are considered to be nonnucleophilic. Methyl radicals are somewhat more reactive toward alkenes bearing electron-withdrawing substituents than towards those with electron-releasing substituents. However, much of this effect can be attributed to the stabilizing effect that these substiments have on the product radical. There is a strong correlation of reaction rate with the overall exothermicity of the reaction. Hydroxymethyl and 2-hydroxy-2-propyl radicals show nucleophilic character. The hydroxymethyl radical shows a slightly enhanced reactivity toward acrylonitrile and acrolein, but a sharply decreased reactivity toward ethyl vinyl ether. Table 12.9 gives some of the reactivity data. 

Minisci reactions have also been applied to these compounds. formation by exposure to w-CPBA and O-methylation with Meerwein s reagent converted 54 into 55. Nucleophilic attack of the hydroxymethyl radical, generated with ammonium sulfate, provides an alternate route to 2-hydroxymethyl pyridines 56. 

Organometallic radicals are important intermediates in biological and catalytic reactions. The structure and formation mechanism of radicals trapped in y-irradiated molecular sieves exposed to methanol and ethylene have been studied by EPR spectroscopy. It was found that Ag CH2OH+ radical with one-electron bond between Ag and C is formed by the attack of -CH2OH hydroxymethyl radical on Ag+ cation. 

Grotheer, H.-H., G. Riekert, D. Walter, and Th. Just, Non-Arrhenius Behavior of the Reaction of Hydroxymethyl Radicals with Molecular Oxygen, J. Phys. Chem., 92, 4028-4030 (1988). 

The conformational barriers in acyclic radicals are smaller than those in closed-shell acycles, with the barrier to rotation in the ethyl radical on the order of tenths of a kilocalorie per mole. The barriers increase for heteroatom-substituted radicals, such as the hydroxymethyl radical, which has a rotational barrier of 5 kcal/mol. Radicals that are conjugated with a n system, such as allyl, benzyl, and radicals adjacent to a carbonyl group, have barriers to rotation on the order of 10 kcal/mol. Such barriers can lead to rotational rate constants that are smaller than the rate constants of competing radical reactions, as was demonstrated with a-amide radicals, and this type of effect permits acyclic stereocontrol in some cases. "... 

The methoxy radical may also be converted to the hydroxymethyl radical (CH2OH) by reaction with methanol,... 

The two isomers CH3O and CH2OH have quite different reaction characteristics. The hydroxymethyl radical mainly reacts with oxygen to form the second desired end product, formaldehyde ... 

This third primary process produced the hydroxymethyl radical which was needed to explain the third low energy peak in the translational energy distribution curve. From the areas associated with each of the peaks in the translational distribution curves they were able to determine that the relative quantum yields for each of these primary process were 9,4,1, and respectively, for reactions 19, 20, and 21. 

These redox chain reactions, which cycle iron(II) and iron(III), have advantages over methods that use stoichiometric quantities of oxidants because the hydroxymethyl radical is also a good reductant and, at high oxidant concentrations, it may be oxidized more rapidly than it adds to (72). The disadvantage of this type of reaction is that the initial radical is generated by a relatively non-selective hydrogen atom abstraction reaction. To be efficient, the H-donor must be used in large excess it is often a cosolvent. Nonetheless, this is a very practical method to prepare hydroxyalkylated and acylated heteroaromatic and related derivatives. 

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). 

The reduction of disulfides is also only given by the hydroxymethyl radical anion [reaction (18)] while the hydroxymethyl radical itself is practically unreac-tive (Akhlaq et al. 1989). 

The 2-hydroxy-2-propyl radical anion is a stronger reductant than the hydroxymethyl radical anion. Thus, a number of reactions are readily given by the for-... 

It is important to note that the rate of reaction of alkyl radicals with thiols does not simply correlate with the exothermicity of the reaction, i.e., with the BDE of the C-H bond to be formed. For example, the tertiary 2-hydroxypropyl radical reacts more readily with thiols than the primary hydroxymethyl radical, and this reacts even faster than the methyl radical (Table 6.4). The reason for this surprising behavior has been discussed in terms of the charge and... 

Schuchmann H-P, von Sonntag C (1988) The oxidation of methanol and 2-propanol by potassium peroxodisulphate in aqueous solution free-radical chain mechanisms elucidated by radiation-chemical techniques. Radiat Phys Chem 32 149-156 Schuchmann H-P, Wagner R, von Sonntag C (1986) The reactions of the hydroxymethyl radical with 1,3-dimethyluracil and 1,3-dimethylthymine. Int J Radiat Biol 50 1051-1068 Schuchmann MN, von Sonntag C (1982) Determination of the rate constants of the reactions C02 + OH" -> HC03 and barbituric acid —> barbiturate anion + H+ using the pulse radiolysis technique. Z Naturforsch 37b 1184-1186... 

The disulfide radical anions are also formed upon the reduction of the disulfide by C02- [reaction (41)] and the thymine radical anion (Willson 1970 Elliot et al. 1984). For example, the reducing hydroxymethyl radical can reduce the disulfide (Anderson et al. 1986), but the rate is only fast when the hydroxymethyl radical is deprotonated (Akhlaq et al. 1989) and thus its redox potential decreased. 

Schoneich C, Dillinger U, von Bruchhausen F, Asmus K-D (1992) Oxidation of polyunsaturated fatty adds and lipids through thiyl and sulfonyl radicals reaction kinetics, and influence of oxygen and structure of thiyl radicals. Arch Biochem Biophys 292 456-467 Schuchmann H-P, von Sonntag C (1981) Photolysis at 185 nm of dimethyl ether in agueous solution Involvement of the hydroxymethyl radical. J Photochem 16 289-295 Schuchmann H-P, von Sonntag C (1997) Fleteroatom peroxyl radicals. In Alfassi ZB (ed) Peroxyl radicals. Wiley, Chichester, pp 439-455... 

Schuchmann H-P, Wagner R, von Sonntag C (1986) The reactions of the hydroxymethyl radical with... 

This chapter discusses an entirely different approach to the generation and investigation of highly reactive transient intermediates. The high reactivity is usually due to an unusual electron distribution in the intermediate that was acquired in the course of the chemical reaction. This implies that for an electron rich intermediate there is a corresponding stable cation in which the electron density was lowered by ionization. Likewise, for an electron-deficient intermediate there is a corresponding stable anion in which the electron deficiency was alleviated by electron attachment. Equations (1) and (2) show simple examples of the methoxy and hydroxymethyl radicals, respectively, which are isomeric transient intermediates of hydrogen atom abstraction from methanol ... 

This scheme of interrelated primary photochemical and subsequent radical reactions is comphcated by the back reaction of hydrogen atoms and hydroxyl radicals with formation of water (Fig. 7-16, reaction 2) or the dimerization of the latter with formation of hydrogen peroxide (Fig. 7-16, reaction 3). Furthermore, hydroxyl radicals are scavenged by hydroperoxyl radicals with formation of oxygen and water (Fig. 7-16, reaction 5) or by hydrogen peroxide to yield hydroperoxyl radicals and water (Fig. 7-16, reaction 4). In addition, hydroxymethyl radicals (HOCH ) formed by reaction 1 (Fig. 7-16) are able to dimerize with formation of 1,2-ethane-diole (Fig. 7-16, reaction 7) or they disproportionate to yield methanol and formaldehyde (Fig. 7-16, reaction 8). 

Radical anions of carbonyl groups and imines also seem to be produced in the presence of titanium (IV) chloride in methanol as solvent. Consecutive oxidation and deprotonation of methanol leads to hydroxymethyl radicals which combine with the carbonyl radical anions to give 1,2-diols and 1,2-aminoalcohols, respectively. The synthesis of the pheromone frontalin has been achieved in a one-pot reaction by hydroxy-methylation of a diketone [127-129]. Likewise triplet sensitizers [130] can be used for direct excitation of the substrate in methanol [131]. Chiral aldimines can be conveniently hydroxymethylated with moderate diastereoselectivity by irradiation of methanolic solutions in the presence of an excess TiCU (Scheme 34) [132]. 

It has been shown that one of the major processes is the scission of an 0-H bond. The resulting radical is unstable and largely fragments into formaldehyde and a hydroxymethyl radical (Scheme 5). The same reaction has been proposed to account for some products in the photolysis of 2-methoxyethanol (159). The formation of molecular hydrogen together with glycolaldehyde, as well as the fragmentation into formaldehyde and methanol (Scheme 5) were postulated as molecular processes in order to account for the products and their quantum yields. 

In order to evaluate fluoroheteroaromatic compounds as intracellular pH probes, R.A.J. Smith and co-workers prepared monofunctionalized polymethylated pyridines. To this end, radical Minisci-type substitution reactions were used on substituted pyridines. Reaction of hydroxymethyl radicals with A/-methoxy 2,4- and 2,6-dimethylpyridinium salts gave 2,4,6-substituted hydroxymethylpyridines. Similar reactions with 2,3,5,6-tetramethylpyridine and derivatives failed, but substitution at the 4-position could be achieved using a carbamoyl radical to yield 2,3,5,6-tetramethyl isonicotinamide, which suggested that steric and reactivity restrictions can be overcome by appropriate choice of the reactive radical intermediate. 

Both reactions are strongly endothermic, proceed very slowly, and do not play any role in subsequent rearrangements of the methoxy and hydroxymethyl radicals. 

The rate constants for the CH3OH + Cl reaction system were derived by Jodkowski et al.30 using the same method which was first applied to describe the kinetics of the reaction of methanol with fluorine atoms.29 The rate constant calculated for the formation of hydroxymethyl radicals kCi(CH2OH) can be expressed in the temperature range 300 - 1000 K as... 

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