Methyl-substituted phenol oxidation

Some simple biphenols equipped with methyl groups, e.g., 3,3, 5,5 -tetramethyl-2,2 -biphenol 38, have attracted attention as important components of highly potent ligand systems [75-86]. Remarkably, the sustainable synthesis of such biphenols is rather challenging despite their simple scaffolds. In particular, methyl-substituted phenols are prone to side reactions. This is especially the case when 2,4-dimethyl-phenol (37) is oxidatively treated. Upon anodic conversion 37 is preferably transformed into polycyclic architectures [87]. Direct electrolysis in basic media provided only traces of the desired biphenol 38 and the dominating components of the product mixture consisted of Pu in meter s ketone 39 and the consecutive pentacyclic spiro derivative 40 [88]. For an efficient electrochemical access to 3,3, 5,5 -tetramethyl-2,2,-biphenol (38) we developed a boron-based template strategy [89, 90]. This methods requires a multi-step protocol but can be conducted on a multi-kilogram scale (Scheme 17). 

The oxidation of methyl groups of aromatic compounds by CuO-NaOH has been found to be ineffective. Therefore, relatively large amounts of methyl-substituted phenolic and benzene carboxylic acids were isolated from the coal oxidation. 

The selective oxidative phenolic orf/io-coupling reaction of simple methyl-substituted phenols turned out to be challenging [12]. When 2,4-dime thy Iphenol (1) is treated by conventional or electro-organic methods, not only the desired biphenol (2) is formed but rather a plethora of polycyclic architectures (Scheme 2) is observed. The major product is Pummerer s ketone (3) and related compounds with a wide structural diversity [13-16]. Application of a boron tether ameliorated the situation tremendously, and biphenol (2) was obtained as the major product [17, 18]. This templated anodic oxidation of 1 represents a multistep process but is suitable for the electro-organic synthesis of (2) on larger scale (see entry Electrosynthesis Using Template-Directed Methods ) [19]. 

As described above, the enzymatic polymerization of phenols was often carried out in a mixture of a water-miscible organic solvent and a buffer. By adding 2,6-di-0-methyl-(3-cyclodextrin (DM-(3-CD), the enzymatic polymerization of water-insoluble m-substituted phenols proceeded in buffer. The water-soluble complex of the monomer and DM-(3-CD was formed and was polymerized by HRP to give a soluble polymer. In the case of phenol, the polymerization took place in the presence of 2,6-di-O-methyl-a-cyclodextrin (DM-a-CD) in a buffer. Only a catalytic amount of DM-a-CD was necessary to induce the polymerization efficiently. Coniferyl alcohol was oxidatively polymerized in the presence of a-CD in an aqueous solution. ... 

Figure 10.11 offers the general reaction network for the SCWO of cresol. This network shows three parallel paths for the oxidation of cresol by SCW. Three reaction intermediates are a hydroxybenzaldehyde via oxidation of the methyl substitute ring-opening products and phenol via demethylation. The end products are COz and HzO. The relative importance of the parallel pathways depends on the specific cresol isomer being oxidized. Figure 10.11 shows that phenol and hydroxybenzaldehydes are key organic intermediates in the reaction network, so the reaction network should also include the reaction paths for these compounds. Two parallel primary paths produce... 

Oil-containing adhesives might emit fatty acid oxidation products like saturated and unsaturated aldehydes which can contribute to odor (Wilke, Jann and Brodner, 2004). Adhesives on a phenol resin base have been found responsible for odor annoyance in several office buildings in former East Berlin. Alkyl-substituted phenols, methyl, dimethyl and ethyl phenols, some of which have very low odor thresholds, have been detected in indoor air as well as in different floor samples and were most likely responsible for the off-odor (Kirchner and Pernak, 2004). 

Tris (f-butyl) phenoxy-, 4,4 -methylenebis (2,4- di-f-butyl) phenoxy- or 4,4 -thiobis (2-t-b utyl-6-methyl) phenoxy-radicals have been prepared for ESR observation by oxidation of the corresponding phenolates at a graphite electrode in acetonitrile 561). Dimroth etaL S62 determined reversible le -oxidation potentials for a series of substituted phenols in basic medium. (CF3)2NOH has been oxidized in alkaline medium on platinum or magnetite in quantitative yield to the pink violet hexafluorodimethylnitroxide (CF3)2NO 563 ... 

Oxidative coupling has been observed for benzene (52), methyl substituted benzenes (53), triphenylethylene (54), triphenyl-amines (55-59), anilines (57), carbazoles (60,61), iminobibenzyls (62), and heterocyclic phenols (71,72). Intramolecular anodic coupling reactions are used for synthesizing specific ring structures (63-68). Both dimer and octamer of dibenzothiophene have been detected (69,70)... 

In the case of the rhenium-catalyzed oxidation of methoxy- and hydroxy-substituted substrates, there is some complementary work concerning the general mechanism of the arene oxidation [10b, 11]. Since the major products in the oxidation of such arenes or phenols are the quinones, the formation of intermediary epoxides seems to be a predominant reaction step. When p-substituted phenols such as 2,6-di( -butyl)-4-methylphenol are treated with the MTO/H2O2 oxidant and acetic acid as solvent, the formation of hydroxydienones is observed. This is also reported for the oxidation using dimethyldioxirane as oxidant [20]. Since an arene oxide intermediate was postulated for the dioxirane oxidation, a similar mechanism is plausible here [11], e. g., for the oxidation of l,2,3-trimethoxy-5-methylbenzene (Scheme 3) or 2,6-di(f-butyl)-4-methyl-phenol. 

The kinetic characteristics were measured for the rearrangements of arene oxides of benzo[a]anthracene, its methyl-substituted derivatives as well as for other polycyclic arene oxides (for transformations of arene oxides into phenols, see Section VII.C). The mechanism of these acid-catalyzed rearrangements and the isotope effects in these reactions were discussed. ... 

Oxidation of p-substituted phenols with f-BuOOH catalyzed by heteropoly acids such as H3PMoi2O40-nH2O (283) and H4SiWi2O40-nH2O has been carried out ". When 2,6-di(ferf-butyl)-4-methylphenol (69) was stirred with 80% f-BuOOH in the presence of 283 in AcOH (30 °C, 3 h), it afforded 2,6-di(terr-butyl)-4-(terr-butylperoxy)-4-methyl-2,5-cyclohexadienone (284) and 2,6-di(terf-butyl)-p-benzoquinone (74) in 62 and 13%... 

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