Substitution, Addition and Intramolecular Reactions

These processes can involve either the ring or the reactive benzylic position. C-Sulphomethylation of 4-dodecylphenol was effected by refluxing with sodium sulphite and aqueous formaldehyde for 20 hours under nitrogen (ref.54). 

4-Ethylphenol and 2,3-dichloro-5,6-dicyanoquinone in equimolecular proportions in methanolic solution gave at ambient temperature 4-(1-methoxyethyl)phenol with a selectivity of 87%, and a conversion of 89% (ref.55). 

Preferential acetylation of the alcoholic hydroxyl group in 4-hydroxymethylphenol was achieved in 60% yield by the use of a little boron trifluoride etherate in acetic anhydride added dropwise to the phenolic alcohol in tetrahdrofuran at 0°C followed by reaction during 4 hours (ref.56). 

In diols containing both phenolic and alcoholic hydroxyl groups neutral conditions favour the acylation of the latter while the former are selectively acylated in the presence of triethylamine (ref. 57) doubtless due to the more nucleophilic phenoxide ion so formed, which is the basis of the Chattaway procedure originated many years ago. This is exemplified in the preferential formation in 95% yield of the phenolic acetate of estradiol in isopropanol containing 2.9 moles of sodium hydroxide in concentrated solution followed by the addition of 2.9 moles of acetic anhydride and then by stirring of the mixture for SOmins. at ambient temperature with maintenance of the pH at 7.8 (ref.58). 

Phenolic formates are generally troublesome to form but 4-tert-butylphenyl-formate resulted in 80% yield by the addition of dicyclohexyldiimide (1.4 moles) to a mixture of 4-tert-butylphenol and formic acid (1.2 moles) in dry dichloromethane followed by reaction during 20 hours at ambient temperature (ref.59). 

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