Ring Substitution and C-acylations

Formylation of 3-aminophenols leading to intermediates for the synthesis of coumarins and other carbonyl derivatives has been described. Nuclear formylation of 3-dimethylaminophenol with ethyl orthoformate in the presence of 4-nitroaniline by boiling for 5 mins, resulted in formation of 2-hydroxy-4-dimethylaminobenzylidene-4-nitroanHine in 88% yield (ref. 100). 

3-Ethylamino-4-methylphenol in dimethylformamide at 120 C treated gradually with 3-amino-1-oxoisoindoline hydrochtoride and then reacted in the hot for 1 hour afforded a 94% yield of 3-(4-ethylamino-2-hydroxy-5 methylphenyl)-1-oxoisoindolinone, hydrolysis of which by refluxing with 20% 

0-Directed metallation followed by carbonation has given an efficient route to 

6-hydroxyanthranilic acid from 3-aminophenol (ref. 102). The amino group was first protected by reaction in sodium bicarbonate solution with pivabyl chloride and then the phenate from sodium hydroxide solution with chloromethyl methyl ether. The isolated doubly protected derivative was lithiated at the 2-position with butyllithium, carbonated and finally hydrolysed with methanolic hydrochloric acid. 

Oxidative arylation of 1,4-naphthoquinone with 3-diethylaminophenol was effected by stirring an acetic acid solution of the mixture containing cupric acetate monohydrate at 50 C for 7 hours to afford 2-[2-hydroxy-4-(diethylamino)phenylj-l, 4-naphthoquinone in 71%yield (ref. 103). 

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