Hydroxylation phenols

Ion-exchange resins. The constituent phenolic hydroxyl groups in the insoluble phenol-formaldehyde resins react with cations of salts ... 

The phenolic hydroxyl group of tyrosine, the imidazole moiety of histidine, and the amide groups of asparagine and glutamine are often not protected in peptide synthesis, since it is usually unnecessary. The protection of the hydroxyl group in serine and threonine (O-acetylation or O-benzylation) is not needed in the azide condensation procedure but may become important when other activation methods are used. 

Carboxyl and acyl groups take precedence over the phenolic hydroxyl m deter mining the base name The hydroxyl is treated as a substituent m these cases... 

The best known aryl ester is O acetylsalicylic acid better known as aspirin It is pre pared by acetylation of the phenolic hydroxyl group of salicylic acid... 

Other Methods. A variety of other methods have been studied, including phenol hydroxylation by N2O with HZSM-5 as catalyst (69), selective access to resorcinol from 5-methyloxohexanoate in the presence of Pd/C (70), cyclotrimerization of carbon monoxide and ethylene to form hydroquinone in the presence of rhodium catalysts (71), the electrochemical oxidation of benzene to hydroquinone and -benzoquinone (72), the air oxidation of phenol to catechol in the presence of a stoichiometric CuCl and Cu(0) catalyst (73), and the isomerization of dihydroxybenzenes on HZSM-5 catalysts (74). 

Chemical Properties. Lignin is subject to oxidation, reduction, discoloration, hydrolysis, and other chemical and enzymatic reactions. Many ate briefly described elsewhere (51). Key to these reactions is the ability of the phenolic hydroxyl groups of lignin to participate in the formation of reactive intermediates, eg, phenoxy radical (4), quinonemethide (5), and phenoxy anion (6) ... 

Alkylphenols can be synthesized by several approaches, including alkylation of a phenol, hydroxylation of an alkylbenzene, dehydrogenation of an alkylcyclohexanol, or ring closure of an appropriately substituted acycHc compound. The choice of approach depends on the target alkylphenol, availabihty of the starting materials, and cost of processing. The procedures discussed herein encompass commercial methods, general methods, and a few specific examples of commercial interest. 

The effect substitution on the phenolic ring has on activity has been the subject of several studies (11—13). Hindering the phenolic hydroxyl group with at least one bulky alkyl group ia the ortho position appears necessary for high antioxidant activity. Neatly all commercial antioxidants are hindered ia this manner. Steric hindrance decreases the ability of a phenoxyl radical to abstract a hydrogen atom from the substrate and thus produces an alkyl radical (14) capable of initiating oxidation (eq. 18). 

Codeine, like morphine, is isolated from the opium poppy. However, the low yield of 0.7—2.5% does not provide sufficient material to meet commercial demands. The majority of marketed codeine is prepared by methylating the phenolic hydroxyl group of morphine. Morphine yields from opium poppy are 4—21%. When prescribed for cough, the usual oral dose is 10—20 mg, three to four times daily. At these doses, adverse side effects are very few. Although the abuse potential for codeine is relatively low, the compound can substitute for morphine in addicts (47). 

The 4-(dimethylaminocarbonyl)benzyl ether has been used to protect the phenolic hydroxyl of tyrosine. It is stable to CF3CO2H (120 h), but not to HBr/AcOH (complete cleavage in 16 h). It can also be cleaved by hydrogenolysis (H2/Pd-C). ... 

If 2 eq. of reagent are used, both hydroxyls can be protected and the phenolic hydroxyl can be selectively cleaved with NaOMe. The te trafluoropyridyl derivative is introduced under similar conditions. The use of this methodology has been reviewed. ... 

Above 160°C it is believed that additional cross-linking reactions take place involving the formation and reaction of quinone methides by condensation of the ether linkages with the phenolic hydroxyl groups (Figure 23.14). 

Polymer systems are now available which may be cured by reaction of epoxy resin compounds with the phenolic hydroxyl groups. Such reactions do not evolve volatile by-products. These materials are showing promise in the area of heat-resisting electrical insulation laminates. 

In summary, it is clear that methylolation is a bimolecular, second-order reaction. As methylol groups are added to the ring, the ring undergoes general activation. Addition of o-methylol groups increases the acidity of the phenolic hydroxyl, which could increase reaction rates. However, all methylol groups ap-... 

These two experiments make a number of important points. An <7-HMP will not react with an ortho position as long as a para reaction site is available. A p-HMP will react with unoccupied ortho position at about half the rate that it reacts with a substituted para position. This suggests that there is something special about the repulsion between the phenolic hydroxyls. Since the pH was only 8, it is clear that there was ample opportunity for a salted 2-HMP to find and react with an unsalted 2-HMP. Both species were present. On this basis, we cannot invoke repulsion of like-charged ions. According to Jones salted species probably react with unsalted species and this is one reason that reaction rate drops rapidly when PF pH gets much above 9.0 [147]. Yet the phenolic hydroxyl appears to be the cause of the reduced reactivity of the ortho position. Unfortunately, Jones did much of his work in a carbonate buffer. He did not realize the pH-dependent accelerating effects of carbonate on PF condensation. 

The three alkaloids concerned, morphine, codeine and thebaine, all behave as tertiary bases. Morphine contains two hydroxyl groups of which one is phenolic and the other a secondary alcohol group. On methylation of the phenolic hydroxyl codeine results. On oxidation, codeine is transformed into codeinone by conversion of the secondary alcohol group into a carbonyl group, and when thebaine is boiled with A-sulphuric acid for a few minutes, it is hydrolysed into codeinone and methyl sulphate, and in other ways thebaine has been shown to contain two methoxyl groups. That the relationship between the three alkaloids is close may be illustrated by the following slightly extended formula —... 

The stereoisomeric pair, morphine and a-womorphine, on methylation of the phenolic hydroxyl at C, give rise to codeine and isocodeine respectively, and similarly and y-i omorphines produce [Pg.250]

EtOH), is insoluble in benzene or ether, and sparingly in chloroform, but dissolves readily in alkali, the solution darkening in air. The salts are crystalline but unstable. The base forms a crystalline metbiodide and contains two methoxyl and two phenolic hydroxyl groups. On methyla-tion it yields a mixture of corydine and fsocorydine. On exhaustive methylation corytuberine yields eventually trimethylamine and 3 4 5 6-tetramethoxy-8-vinylphenanthrene, m.p. 69°. 

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