Phenols ortho effect

Resole syntheses entail substitution of formaldehyde (or formaldehyde derivatives) on phenolic ortho and para positions followed by methylol condensation reactions which form dimers and oligomers. Under basic conditions, pheno-late rings are the reactive species for electrophilic aromatic substitution reactions. A simplified mechanism is generally used to depict the formaldehyde substitution on the phenol rings (Fig. 7.21). It should be noted that this mechanism does not account for pH effects, the type of catalyst, or the formation of hemiformals. Mixtures of mono-, di-, and trihydroxymethyl-substituted phenols are produced. 

Dielectric studies have been applied principally to the problem of deciding between several possible structures. A typical H bonded example may be taken from one of Curran s papers (467) o-methoxy-phenol (guaiacol) has two possible planar configurations whose dipole moments, as calculated by the vector addition method, are widely different (Fig. 5-3). The measured value of 2.41 d indicates that the intra-molecularly H bonded form exists in the benzene and dioxane solutions used. A large number of phenols, aniline derivatives, and other disub-stituted aromatic compounds have been studied in a similar fashion, and the wide occurrence of the ortho effect has been demonstrated. If two adjacent positions of the ring have proper substituents, a H bond will form. 

Bijloo, G.J. and Rekker, R.F. (1984a). Some Critical Remarks Concerning the Inductive Parameter Oi. Part III Parametrization of the Ortho Effect in Benzoic Acids and Phenols. Quant. Struct.-Act.Relat, 3,91-96. 

The ionized dihydroxybenzenes 39" behave similarly (Scheme 17). Note that, in this series, one of the phenolic hydroxyl groups acts as a hydrogen acceptor and the other as an H donor. The El mass spectrum of catechol (o-39) exhibits a significant ortho effect. While the intensity of the [M — H20]" peak in the El spectrum of o-39 is no greater than ca 15%B, the spectra of resorcinol (m-39) and hydroquinone (p-39) both show negligibly smah [M — H20] + peaks ( 2%B). It is likely that water loss from the intermediate 47 generates again bicyclic [M — H20]" ions, i.e. ionized benzoxirene 48. And, notably, the CO losses does not parallel the ortho effect of the water elimination in this series, as it is the most pronounced ion the case of m-2>9. 

The transition between simple dependence on lipophilicity to exclusive dependence on reactivity factors led us to consider two separate classes of phenol toxicity as discussed in the conclusions. In addition, the clear dependance on steric or "ortho" effects for... 

Transposition of substituents takes place from aromatic compounds based on ortho effects from hydroxyphenyl ketones via assumed nucleophilic attack on the carbonyl carbon atom of the phenoxide site to give a tight tetravalent intermediate that promptly decomposes through benzyne neutral release and formation of a carboxylate anion (Scheme 17.19a). This reaction is hindered from meta- and para-substituted phenols. Alternatively, radical alkane loss is also observed that can be rationalized by considering the formation of an ion-neutral complex (Scheme 17.19b) comprised of quinone-like and alkylide groups. The relatively low ionization energy allows the generation of odd-electron quinone-like species and the elimination of the alkane radical (Scheme 17.19b). 

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). 

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. 

Unlike the acid-catalyzed ether cleavage reaction discussed in the previous section, which is general to all ethers, the Claisen rearrangement is specific to allyl aryl ethers, Ar—O—CH2CH = CH2. Treatment of a phenoxide ion with 3-bromopropene (allyl bromide) results in a Williamson ether synthesis and formation of an allyl aryl ether. Heating the allyl aryl ether to 200 to 250 °C then effects Claisen rearrangement, leading to an o-allylphenol. The net result is alkylation of the phenol in an ortho position. 

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