Reactivity of phenols

Nitration Phenols are nitrated on treatment with a dilute solution of nitric acid in either water or acetic acid. It is not necessary to use mixtures of nitric and sulfuric acids, because of the high reactivity of phenols. 

Phenol ethers show some, admittedly low, reactivity towards diazonium ions and also undissociated phenols (see Sec. 12.7). An instructive example of the reactivity of phenol ethers was reported by Ronaldson (1981). He found that 1,2-dimethoxy-benzene (veratrole) does not react with the 4-nitrobenzenediazonium ion, but the azo coupling product is formed when the more electrophilic 2,4-dinitrobenzenediazo-nium ion is used. 

The reactivity of phenols depends on several structural factors, as well as on the conditions of oxidation (solvent, temperature). Let us discuss the main factors that determine phenol reactivity. This analysis will be performed within the scope of IPM (see Chapter 6). 

Tertiary alkyl substituents in the ori/zo-position to the phenolic group cause an additional repulsion in TS and, hence, diminish the reactivity of phenols. Using values of Ee0 for ArjOH and sterically hindered Ar2OH, we can estimate the contribution from such a steric repulsion AES to the activation energy E [33,34],... 

The same effect is typical of the reactions of alkoxyl radicals with phenols, that is, these reactions are much slower in solvents capable of forming hydrogen bonds with O—H and N—H groups [50]. MacFaul et al. [50] proposed a universal scale for correlating the reactivities of phenols and the hydrogen-bonding abilities of solvents. 

It is apparent that the high reactivity of phenols is due to the absence of triplet repulsion (AEr 0), whereas that of aromatic amines results from a large difference in the electronegativities of nitrogen and oxygen atoms (AEea = -20 kJ mol-1). 

The reactivity of phenols to electrophilic nitration is illustrated further by the facile conversion of m-nitrophenol to 2,3,4,6-tetranitrophenol with anhydrous mixed acid. The latter is a powerful explosive, but chemically unstable, like all polynitroarylenes containing a nitro group positioned olp- to other nitro groups. 

Cheynier, V. et al., Reactivity of phenolic compounds in wine diversity of mechanisms and resulting products. In In Vino Analytica Scientia, Bordeaux, 1997, p. 143. 

The reactivity of phenols in the Cu-complex-catalyzed oxidation was studied by measuring the oxidation rate, the rate constant ke, and the redox potentials of the Cu complex and of the phenol (Fig. 29)158). The logarithm of the oxidation rate is proportional to log ke, which supports the assumption that the electron-transfer step is rate-determining. A linear relationship is observed between log ke and Hammett s o value of the phenol, which is proportional to the oxidation potential of the phenol. 

However, the reactivity of phenolic hydroxy groups can be modified by a fused heterocyclic ring. Thus, hydroxy groups peri to a carbonyl group, e.g. (600), are hydrogen bonded they do not react with diazomethane, and are difficult to acylate. This allows selective reactions in polyhydroxychromones. 

The effect of substituents on the reactivity of phenols with epichlorohydrin hot been examined also by Bradley and co-workers.283 In contrast with earlier observations made by Boyd and blade with othyfene oxide and propylene oxide, the most acidio phenols are the ones giving maximum yields with epichlorohydrin. This indicated that in this particular reaction the relative concentration of phenoxide ions rather than their nucleophiBcity is the overriding factor in determining the rates of addition. 

Since phenol is benzene with a hydroxyl group, the reactivity of phenol and phenolic compounds is in many ways dictated by the chemical properties of the benzene ring. The first property to consider is acidity. A compound is considered an acid when it can release a proton (H ) while in solution. The acid constant Ka of a compound defines to what extent the proton is released. Strong acids will completely dissociate, whereas weak acids (HA) are at equilibrium with their dissociated state ... 

The available rate data for the substitution reactions of phenol, diphenyl ether, and anisole are summarized in Table 5. The elucidation of the reactivity of phenol is hindered by its partial conversion in basic media into the more reactive phenoxide anion. Because of the high reaction velocity of phenol and the even greater reactivity of phenoxide ion the relative rates are difficult to evaluate. Study of the bromination of substituted phenols (Bell and Spencer, 1959 Bell and Rawlinson, 1961) by electrochemical techniques suitable for fast reactions indicates the significance of both reaction paths even under acidic conditions. 

The one-step hydroxylation ofbenzene represents an attractive alternative pathway for the direct synthesis of phenol and many studies are performed using different processes among which the photocatalytic reaction [45,46]. One of the main problem is the low selectivity of the process due to the higher reactivity of phenol towards the oxidation than benzene with the formation of oxidation by-products. In order to avoid these secondary products and to obtain the separation of the phenol from the oxidant reaction environment the use of a membrane system coupled with the photocatalytic process seems a useful solution. 

Direct oxidation of benzene to phenol is of great interest not only for its industrial importance, but also from a purely scientific point of view. Apart from many earlier reports [35] on the oxidation of benzene to phenol by hydroxyl radicals generated by the reaction of Fe2+ salt (Fenton reagent) with H202 not much is known about the homogeneously catalysed oxyfunctionalization of aromatic C-H bonds. The lack of studies is largely attributable to the fact that the activation of the C-H bond in benzene is difficult owing to its resonance stability and the reactivity of phenol, which is consecutively oxidized to quinones and other by-products. 

The presence of a large number of hydroxyl groups in the ring increases the reactivity of phenol very considerably. That is why these compounds are very easy to nitrate, and in the nitration process by the conventional method for phenols,... 

The radical reactivity of phenols is markedly influenced by substitution. In this paragraph, the substituent effect will be treated in terms of the Hammett equation. All possible substituted phenols are considered except those having t-butyl groups in both ortho positions which are dealt with under IIC. It could be questioned whether phenols containing or(Ao-substituents other than t-butyl groups would not also cause steric... 

Similarly, the reactivity of phenolate ions as the tetra- -butylammonium salt has been shown to be 3 10" times higher than that of the corresponding potassium salt in the Sn2 alkylation reaction with 1-halobutanes, carried out in 1,4-dioxane [340], Whereas the rate of alkylation of the potassium salt increases by a factor of ca. 10 on going from 1,4-dioxane (fir = 2.2) to iV,iV-dimethylformamide (e, = 36.7), the alkylation rate of the quaternary phenolate is essentially insensitive to the same solvent change. Obviously, the phenolate ion combined with the larger ammonium ion is already very reactive because of the relatively weak cation-anion interaction in the ion pair. In such cases, dissociation to a truly free anion does not seem to be required in order to explain the high reactivity [340]. 

Resorcinol Resins. The reactivity of phenol with formaldehyde is greatly increased with two hydroxyl groups on its nucleus (resorcinol VIII). Room temperature polymerization is observed without the need for any catalyst. The rate of reaction goes through a minimum at a pH of 3.5 and increases at lower or higher pH values. To make a useful adhesive, prepolymers, similar to novolaks, are pre-... 

The relationship between reactivities of phenolate ion and 4-cyano-phenolate ion is ... 

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