Phenol ring-alkylated, formation

Hydroxyl Group. Reactions of the phenohc hydroxyl group iaclude the formation of salts, esters, and ethers. The sodium salt of the hydroxyl group is alkylated readily by an alkyl hahde (WiUiamson ether synthesis). Normally, only alkylation of the hydroxyl is observed. However, phenolate ions are ambident nucleophiles and under certain conditions, ring alkylation can also occur. Proper choice of reaction conditions can produce essentially exclusive substitution. Polar solvents favor formation of the ether nonpolar solvents favor ring substitution. 

Thioglycohc acid is recommended as a cocatalyst with strong mineral acid in the manufacture of bisphenol A by the condensation of phenol and acetone. The effect of the mercapto group (mercaptocarboxyhc acid) is attributed to the formation of a more stable carbanion intermediate of the ketone that can alkylate the phenol ring faster. The total amount of the by-products is considerably reduced (52). 

Once formed, these acids then degrade to lower-molecular-weight species such as the more easily defined aliphatic and aromatic carboxylic acids. The final step is the formation of the carbon dioxide from these acids. Acids containing polycondensed ring systems are not often detected among the products of the oxidation of coal but there are claims that the mixed aromatic acids from the oxidation of coal with performic acid also contain a variety of phenols and alkyl-substituted phenols (Figure 12.4). 

For carbon-carbon bond-formation purposes, S 2 nucleophilic substitutions are frequently used. Simple S 2 nucleophilic substitution reactions are generally slower in aqueous conditions than in aprotic organic solvents. This has been attributed to the solvation of nucleophiles in water. As previously mentioned in Section 5.2, Breslow and co-workers have found that cosolvents such as ethanol increase the solubility of hydrophobic molecules in water and provide interesting results for nucleophilic substitutions (Scheme 6.1). In alkylations of phenoxide ions by benzylic chlorides, S/y2 substitutions can occur both at the phenoxide oxygen and at the ortho and para positions of the ring. In fact, carbon alkylation occurs in water but not in nonpolar organic solvents and it is observed only when the phenoxide has at least one methyl substituent ortho, meta, or para). The effects of phenol substituents and of cosolvents on the rates of the competing alkylation processes... 

A similar problem of complex formation may be encountered if either amino or phenol groups are present in the substrate, and the reaction may fail. Under such circumstances, these groups need to be blocked (protected) by making a suitable derivative. Nevertheless, Friedel-Crafts acylations tend to work very well and with good yields, uncomplicated by multiple acylations, since the acyl group introduced deactivates the ring towards further electrophilic substitution. This contrasts with Friedel-Crafts alkylations, where the alkyl substituents introduced activate the ring towards further substitution (see Section 8.4.3). 

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