Phenolics occurance

A hydroxyl group is a very powerful activating substituent and electrophilic aro matic substitution m phenols occurs far faster and under milder conditions than m ben zene The hrst entry m Table 24 4 for example shows the monobrommation of phenol m high yield at low temperature and m the absence of any catalyst In this case the reac tion was carried out m the nonpolar solvent 1 2 dichloroethane In polar solvents such as water it is difficult to limit the brommation of phenols to monosubstitution In the fol lowing example all three positions that are ortho or para to the hydroxyl undergo rapid substitution... 

Halogenation Bromination and chlorination of phenols occur readily even in the absence of a cata lyst Substitution occurs primarily at the position para to the hydroxyl group When the para position IS blocked ortho substitution is observed... 

Ammonolysis of phenol occurs in the vapor phase. In the Scientific Design Co. process (Figure 10-10), a mixed feed of ammonia and phenol is heated and passed over a heterogeneous catalyst in a fixed-bed sys-... 

Phenols occur widely throughout nature and also serve as intermediates in the industrial synthesis of products as diverse as adhesives and antiseptics. Phenol itself is a general disinfectant found in coal tar methyl salicylate is a flavoring agent found in oil of wintergreen and the urushiols are the allergenic constituents of poison oak and poison ivy. Note that the word phenol is the name both of the specific compound hydroxybenzene and of a class of compounds. 

In a phenol, a hydroxyl group is attached directly to an aromatic ring. The parent compound, phenol itself, Cr,HsOH (4), is a white, crystalline, molecular solid. It was once obtained from the distillation of coal tar, but now it is mainly synthesized from benzene. Many substituted phenols occur naturally, some being responsible for the fragrances of plants. They are often components of essential oils, the oils that can be distilled from flowers and leaves. Thymol (5), for instance, is the active ingredient of oil of thyme, and eugenol (6) provides most of the scent and flavor of oil of cloves. 

The mechanism of antioxidant action on the oxidation of carbon-chain polymers is practically the same as that of hydrocarbon oxidation (see Chapters 14 and 15 and monographs [29 10]). The peculiarities lie in the specificity of diffusion and the cage effect in polymers. As described earlier, the reaction of peroxyl radicals with phenol occurs more slowly in the polymer matrix than in the liquid phase. This is due to the influence of the polymeric rigid cage on a bimolecular reaction (see earlier). The values of rate constants of macromolecular peroxyl radicals with phenols are collected in Table 19.7. 

Absorption of phenol occurs fairly rapidly via the inhalation (Hughes and Hall 1995 Ohtsuji and Ikeda 1972 Piotrowski 1971), oral (Capel et al. 1972 Edwards et al. 1986 French et al. 1974 Hughes and Hall 1995 Kao et al. 1979 Kenyon et al. 1995), and dermal (Baranowska-Dutkiewicz 1981 Hughes and Hall 1995 Piotrowski 1971) routes. Because it is an irritant, tissue damage, inflammation, or other irritation effects may occur at the sites of absorption. Because of its high pKa, ionization will not occur within the acid environment of the gut. The action of gut microflora on phenol breakdown is not expected to be significant. 

One of the earliest reports of LO inhibition concerned the effects of ortho-dihydroxybenzene (catechol) derivatives on soybean 15-LO [58]. Lipophilic catechols, notably nordihydroguaiaretic acid (NDGA) (19), were more potent (10 /zM) than pyrocatechol itself. The inactivation was, under some conditions, irreversible, and was accompanied by oxidation of the phenolic compound. The orfAo-dihydroxyphenyl moiety was required for the best potency, and potency also correlated with overall lipophilicity of the inhibitor [61]. NDGA and other phenolic compounds have been shown by electron paramagnetic resonance spectroscopy to reduce the active-site iron from Fe(III) to Fe(II) [62] one-electron oxidation of the phenols occurs to yield detectable free radicals [63]. Electron-poor, less easily oxidized catechols form stable complexes with the active-site iron atom [64]. 

Phenol occurs naturally in many plants including blueberries (10 to 60 ppb), marjoram (1,431-8,204 ppm), sweetflag, safflower buds (40 ppb), mud plantain, capillary wormwood, asparagus... 

Cornelius Steelink Perhaps plant cellulosic material, after hydrolysis, could be used by soil microorganisms to produce phenolic substances, which could then be incorporated into humic acids. I think it is significant that nonlignin-derived phenols occur in podzol humic acids. 

Because of their increased acidity, it is possible for phenols to effect total substitution of halide ligands in cases where alcohols cause only partial substitution. Hence, although WC16 reacts with ethanol to give the Wv complex [WCl3(OEt)2]2,35 phenol in benzene gives W(OPh)6 in excellent yields.4,36 Similarly, the phenoxides of Ti,37 Nb and Ta38 have been obtained. In cases where only partial replacement by phenol occurs, the use of substituents that increase the phenolic acidity can sometimes aid the reaction, for example as shown in equation (7).39,4(1... 

Phenol itself can be arylated multiply around the oxygen up to five times by use of excess bromobenzene (Eq. 4) [8]. The use of a less polar solvent such as o-xylene is important no reaction of phenol occurs in DMF. The lack of hexa-arylated product may be attributed to steric reasons. When the 2- and 6-positions of phenol are masked by fert-butyl groups, the 4-position is arylated (Eq. (5) and path b in Scheme 3) [10]. It is worth noting that a diaryl ether is formed by reductive elimination of the alkoxyarylpalladium intermediate when a bulky phosphine ligand is used (path d) [11]. 

The etherification of silicon tetrachloride with anhydrous alcohols or phenols occurs stagewise and can be schematically written thus ... 

The data in Figure 2 for trialkylated phenol products are similar to those in Figure 1, with two important differences. The abrupt change in effectiveness of the trialkylated phenols occurs when R is Ci0H2i to C12H25. Although in the more severe tests these compounds are about as effective as the 2,6-dialkyl-p-cresols, in the least severe test they are considerably less effective. It is evident that 2,4,6-trioctadecylphenol is also a very potent antioxidant. 

Regiocontrol Although Michael additions to [Os]-phenol occur selectively at C4, addition at C2 is thermodynamically favored for phenol complexes that are substituted at C4. For C4-substituted phenol complexes, the regiochemistry can be controlled by varying the time, temperature, and catalyst (Figure 6) [29]. Additions of MVK to the estradiol complex 90 and the p-cresol 94 at —40 °C in the presence of an amine base catalyst result in regioselective C4 alkylation in high yields (91 and 95). However, when this reaction is performed at room temperature in the presence of a Zn2+ co-catalyst, the Michael acceptor adds at C2 to afford... 

It still seems most reasonable to assume that the abstraction of the hydrogen atom from hindered phenols occurs in a direction perpendicular to the plane of the ring. The perpendicular direction can be favoured for the transition state of hindered phenols since it is less covered by the bulky ortho substituents than the coplanar conformation. If, at least, one of the oriAo-positions is free, the abstraction takes place most probably in the plane of the ring. The lifetime of the coplanar conformation can be much longer than that of the perpendicular state, and more molecules are found at a time in the coplanar form than in perpendicular conformation. If the transition state of the hydrogen abstraction is different for hindered and non-hindered phenols, this difference could explain why the pjpBt ratio is fairly constant. 

The reduction of NO is easier than that of N02> and HS is enough to do the job. The amine can now be converted to an amide to lessen its nucleophilicity so that alkylation of the phenol occurs cleanly. 

Equation 4.13 suggests that there ought to be some sort of correlation between the shielding factor and the electron density around the hydrogen. For example, a more acidic proton, such as the OH proton in phenol, should be less shielded than the corresponding less acidic proton in an alcohol. This is indeed found to be the case, the chemical shift for the OH proton of phenol occurring... 

While the mtrosation of phenols occurs at least as readily as that of tertiary aromatic amines -such as dimethylaniline, the conditions must be very carefully controlled owing to the ease with which most phenols oxidize. For this reason a higher proportion of tarry by-products is formed and the yields are smaller than in the case of the dialkylanilines. Taking o-cresol as a typical example of a phenol with an unsubstituted para- position, the main product of the reaction is />-nitroso-o-cresoL... 

The amination of 2-alkenylphenols occurred efficiently compared to 2-allylphenols and -naph-thols69. The mechanism involves a proton exchange equilibrium between the phenolic and amino functions and the photoinduced proton transfer (PPT) from the ammonium ion to the alkenyl group, followed by attack of the amine on the intermediate benzylic carbocation. No photoamination of O-methylated and O-acetylated phenols occurred at all. As a single example of diastereoselective amination, the amine 6 was produced from 5 with good yield and diastereoselectivity, although the configuration was not determined. 

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