Electrophilic substitution on phenols

We started this chapter by comparing phenols with enols and now we return to phenols and look at electrophilic substitution in full detail. You will find that the reaction is much easier than it was with benzene itself because phenols are Uke enols and the same reactions (bromina-tion, nitration, sulfonation, and Friedel—Crafts reactions) occur more easily. There is a new question too the positions round the phenol ring are no longer equivalent—so where does substitution take place  

Benzene does not react with bromine except with Lewis acid catalysis. Phenols react in a very different manner no Lewis acid is needed, the reaction occurs very rapidly, and the product contains three atoms of bromine in specific positions. All that needs to be done is to add bromine dropwise to a solution of phenol in ethanol. Initially, the yellow colour of the bromine disappears but if, when the colour just remains, water is added, a white precipitate of 2,4,6-tribromophenol is formed. 

Why do we use numbers for some descriptions, such as 2,4-dibromophenol but also use ortho and para in others The numbers are best in naming compounds but we need ortho and para to describe the relationship between substituents. Phenol brominates in both ortho positions. In this molecule they happen to be positions 2 and 6. In other molecules, where the OH group is not at Cl, they will have other numbers but they will still be ortho to the OH group. Use whichever description suits the point you are making. 

Now the reaction is repeated, but this time at one of the two equivalent ortho positions  

Again the lone pair electrons on the OH group are fed through the benzene ring to emerge at the ortho position. A third bromination in the remaining ortho position—you could draw the mechanisms for this as practice—ogives the final product 2,4,6-tribromophenol. 

This is not strictly catalysis as a stoichiometric amount of Lewis acid is needed and cannot be recovered. 

Notice that we start the chain of arrows with the lone pair electrons on the OH Qh OKI 

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Coupling with phenoxide ion could take place either on oxygen or on carbon, and though relative electron-density might be expected to favour the former, the strength of the bond that is formed is also of significance. Thus here, as with other electrophilic attacks on phenols, it is found to be the C-substituted product (31) that is formed ... 

Finally, electrophilic substitution on the left-hand ring in the manner of the first nitration step puts in the third and fourth iodine substituents of thyroxine. Notice that the free O- (the phenol is ionized with Et2NH) group is more activating (electron-donating) than the ether oxygen atom. 

The first slajge can be viewed as both electrophilic substitution on the ring by the electron-deficient carbon of forrnaldehyde, and nucleophilic addition of the aromatic ring to the carbonyl group ase catalyzes reaction by converting phenol into the more reactive (more nucleophilic) phenoxide ion.jj Acid catalyzes reaction by protonating formaldehyde and increasing the electron deficiency of the carbonyl carbon.)... 

A striking difference between pyridines and their A-oxides is the susceptibility of the latter to electrophilic nitration. This can be understood in terms of mesomeric release from the oxide oxygen, and is parallel to electron release by oxygen and hence increased reactivity towards electrophilic substitution in phenols and phenoxides. One can find support for this rationalisation by a comparison of the dipole moments of trimethylamine and its A-oxide, on the one hand, and pyridine and its A-oxide, on the other the difference... 

Okajima T (2001) Ab initio MO investigation on the reactivity for electrophilic substitution of phenolic with oxirane and aziridine, as the model compounds of binding site of mutagen. J Mol Struct (THEOCHEM) 536 73-82... 

Bakelite Trademark) A common thermosetting synthetic polymer formed by the condensation of phenol (CgHjOH) and methanal (formaldehyde, HCOH). It is an example of a phenolic resin (or phenol-formaldehyde resin), and was one of the first useful synthetic polymers. The reaction between phenol and methanal occurs under acid conditions and involves electrophilic substitution on the benzene ring to give a three-dimensional polymeric structure. Bakelite is named for the Belgian-born US chemist Leo Hendrik Baekeland (1863-1944), who discovered it in 1909. 

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. 

The literature on basic- and acid-catalyzed alkylation of phenol and of its derivatives is wide [1,2], since this class of reactions finds industrial application for the synthesis of several intermediates 2-methylphenol as a monomer for the synthesis of epoxy cresol novolac resin 2,5-dimethylphenol as an intermediate for the synthesis of antiseptics, dyes and antioxidants 2,6-dimethylphenol used for the manufacture of polyphenylenoxide resins, and 2,3,6-trimethylphenol as a starting material for the synthesis of vitamin E. The nature of the products obtained in phenol methylation is affected by the surface characteristics of the catalyst, since catalysts having acid features address the electrophilic substitution in the ortho and para positions with respect to the hydroxy group (steric effects in confined environments may however affect the ortho/para-C-alkylation ratio), while with basic catalysts the ortho positions become the... 

The difference in position of attack on primary and secondary aromatic amines, compared with phenols, probably reflects the relative electron-density of the various positions in the former compounds exerting the controlling influence for, in contrast to a number of other aromatic electrophilic substitution reactions, diazo coupling is sensitive to relatively small differences in electron density (reflecting the rather low ability as an electrophile of PhN2 ). Similar differences in electron-density do of course occur in phenols but here control over the position of attack is exerted more by the relative strengths of the bonds formed in the two products in the two alternative coupled products derivable from amines, this latter difference is much less marked. 

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