Phenolics chemistry

Brewis M, Clarkson GJ, Humberstone P, Makhseed S, McKeown NB (1998) The synthesis of some phthalocyanines and napthalocyanines derived from sterically hindered phenols. Chemistry-A European Journal 4 1633-1640. 

The major manufacturing process for making phenol was discussed in Chapter 10, Section 4, since it is the co-product with acetone from the acid-catalyzed rearrangement of cumene hydroperoxide. The student should review this process. It accounts for 95% of the total phenol production and has dominated phenol chemistry since the early 1950s. But a few other syntheses deserve some mention. 

Polymerization reaction of acrylonitrile in solution. Fourth report. Retardation of the polymerization reaction by the use of nitro derivatives of phenol. Chemistry High Polymers, Japan 16, 453—455 (1959). 

Although the esterifiction of phenols and also their etherification (considered in the next chapter) can be regarded as protective methods for the phenolic hydroxyl group there have been few developments in this aspect of phenolic chemistry. The definitive text on this topic remains relevant (ref,59). 

Many different aspects of phenolic chemistry have been presented in this account some positive in effect and others appparently less so. The impact of the chemistry of not just phenolic but all chemical compounds on humanity is sometimes, even frequently, misunderstood and the words of a great playwright are relevant (ref. 291). One objective in scientific work is to understand the natural world and to then improve and develop it but human life is itself experimental and the outcome uncertain. 

The chemistry of phenols tends to be ignored in chapters in organic chemical textbooks and to be lost amongst the many classes of functional derivatives. This book is not intended however to provide such a text book approach but to give an account of developments In phenol chemistry in the last two and more decades. It assumes some familiarity with the chemistry of the phenolic ring. 

Maier, V.P. Aspects of plant phenolic chemistry Proc. Plant Phenolics Group of North America (1964). 

In recent years, phenolic compounds have been identified in spruce bark, including stilbenes, flavonoids, and tannins. Studies have looked for changes in phenolic quantity and composition after wounding or fungal infection. However, the changes observed were unremarkable (increase or decrease of 2-fold or less) or poorly replicated. Thus, it is still unclear what changes in phenolic chemistry are associated with the dramatic changes observed in the anatomy of the PP cells. 

Up to this point, we have presented only a general overview of phenolic chemistry with some illustration of applications. We now turn to a more detailed and quantitative discussion of the methylolation process. Though other aldehydes are occasionally used, formaldehyde is overwhelmingly the aldehyde of choice, and we will limit our discussions to phenol-formaldehyde reactions. 

Crozier A, Jaganath IB, Clifford MN. Dietary phenolics chemistry, bioavailability and effects on health. Nat Prod Rep. 2009 26 1001-1043. 

Nyman T, Julkunen-Tiitto R (2000) Manipulation of the phenolic chemistry of willows by gall-inducing sawfiies. Proc Natl Acad Sci USA 97 13184—13187... 

Examples of the use of this group relate mostly to phenol chemistry and to directing substitution ortho to the hydroxyl group. Thus 2,6-dichlorophenol (26) can usefully be prepared by chlorinating p-hydroxybenzoic acid, and decarboxylating the resulting acid (27). The overall yield is 80-90% [26]. 

These ethers (and methoxymethyl) have not found extensive use in phenol chemistry as protecting groups possibly because their lability towards aqueous acid is so much greater than that of the conventional alkyl or benzyl group. One distinction which may be of advantage is that they are formed in the absence of base. Thus they are generated by addition of the phenol to an olefin, isobutylene or dihydropyran, under acid catalysis [12, 18]. The tetrahydropyranyl ether of 2-methyl-4-acetoxy-a-naphthol is thus formed at room temperature in ethyl acetate saturated with hydrogen chloride [18]. 

Trimethylsilyl ethers have similarly found limited use in preparative phenol chemistry and their particular application has often been to confer improved solubility characteristics such as to facilitate analysis and chromatographic separations of complex phenolic mixtures (e.g. flavanoids [37], hydroxy-benzoic acids [25], tetracyclines [38], etc.). The ethers are readily formed by the action of trimethylchlorsilane [24] or hexamethyldisilazane [25] on the phenol. More recently they have been applied in the preparation of phenols which are acid or thermally labile [39, 40, 41] and are not obtainable by alternative techniques. 

Scientific activity continues to grow in both basic research and applications. It is interesting to look at the patents issued by country during the years 1981-1987. The results in Table 2 show substantial commercial development in the phenolic field and also illustrate the large contribution from Japan to the patent literature. In 1982-1986 alone there were 4620 articles, excluding patents, pertaining specifically to phenolic chemistry and technology. 

Phenolics which are formed when the molar ratio of formaldehyde to phenol is greater than one are called resoles. The phenol moieties are terminated with reactive hydroxymethyl groups (—CH2OH), known as methylol groups. If the mole ratio of formaldehyde to phenol is less than one, the polymer becomes phenol terminated and is called a novolak. All phenolic chemistry today revolves about these two basic chemistry strategies. Although phenol is most commonly involved in phenolics, resins containing p-r-butylphenol, p-r-amylphenol, p-nonylphenol, mixed cresols, and substituted... 

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