Benzylic hydroxylation mechanism

Analogous side-chain oxidations occur in various biosynthetic pathways. The neurotransmitter norepinephrine, for instance, is biosynthesized from dopamine by a benzylic hydroxylation reaction. The process is catalyzed by the copper-containing enzyme dopamine /3-monooxygenase and occurs by a radical mechanism. A copper-oxygen species in the enzyme first abstracts the pro-R benzylic hydrogen to give a radical, and a hydroxyl is then transferred from copper to carbon. 

The mechanism proposed in Figure 3 can easily be applied to the oxidative depolymerization of the lignin macromolecule by nitrobenzene or copper(II) in aqueous alkali. A recent model of softwood lignin (24) contains 27% free benzylic hydroxyl groups and 12% aromatic ring-conjugated double bonds (stilbene... 

It is also hypothesized that formation of 2-benzyl-2-hydroxydihydrobenzofuran-3-ones 6 and 2-arylbenzofuran-3-carboxylic acids 7 are derived from an intramolecular attack of the phenoxide at the P-position. Despite the complex mechanism and multiple products, general trends have emerged through experimental results. If the chalcone lacks a 6 -methoxy group but has a hydroxyl group at the C2 or C4 positions, flavonols are favored. However, if the 6 -methoxy group is present and no hydroxyl substituent is present at C2 or C4 aurones and flavonols are formed. Others have also shown that pH and temperature influence the product distribution. 

The oxidation by strains of Pseudomonas putida of the methyl group in arenes containing a hydroxyl group in the para position is, however, carried out by a different mechanism. The initial step is dehydrogenation to a quinone methide followed by hydration (hydroxylation) to the benzyl alcohol (Hopper 1976) (Figure 3.7). The reaction with 4-ethylphenol is partially stereospecific (Mclntire et al. 1984), and the enzymes that catalyze the first two steps are flavocytochromes (Mclntire et al. 1985). The role of formal hydroxylation in the degradation of azaarenes is discussed in the section on oxidoreductases (hydroxylases). 

There are five papers on carbamate chemistry of interest.6,84-87 The mechanism of the reaction in MeCN of /V-mcthyI-/V-phcnyIcarbamoyI chlorides (94) with benzyl-amines is believed to be Sf2 based on Hammett p values, a cross-interaction constant pxy of —0.14, ka/ko values for the /V-dcutcriatcd benzylamines all <1, and low activation enthalpies.84 The aminolysis of /7-nitrophcnyl /V-phenylcarbamatcs in acetonitrile involving the T1 (7) was discussed earlier.6 Solvolysis-decomposition of N- -adamantyl-/V-/7-tolylcarbamoyl chloride (95) in hydroxylic solvents involves a facile slow ionization (SWl mechanism) giving a cation which eliminates ArNCO to... 

Intramolecular protonation on the more hindered face of a steroid from a neighbouring hydroxyl group best explains a reversal of diastereoselectivity in the Birch reduction of styrene double bonds.266 The kinetics and product distribution of lithium metal reduction of benzaldehyde to benzyl alcohol in THF have been studied electron transfer from Li to PhCHO occurs in a slow step, but absorption of the PhCHO onto the metal surface is also crucial in determining the overall kinetics. The proposed mechanism successfully accounts for the formation of minor products, benzoin and... 

---