Synthesis of Nitrophenols

The finding of regiospecific routes to the nitrophenols is an important development in an area which has consistently presented difficulty in this respect. 

The zwitterion, N-dodecylpyridinium-3-carboxylate converted in an acetonitrile suspension with an acetonitrile solution of nitronium tetrafluoroborate to the nitro ester, upon treatment with phenol gave 2-nitrophenol in 95% yield (ref.61). 

It seems possible that other well-known nitro esters might also be effective. Indirect nitration of phenol in ether/water (1 1) by the addition of sodium nitrate and concentrated (11M) hydrochloric ackJ and stirring of the mixture at ambient temperature for more than 12 hours gave the isomeric 2- and 4-nitrophenols in 65% yield with the ratio 3 2 respectively (ref.62). Although this percentage of products is the same as in standard laboratory methods the conditions are essentially milder. 

4-Methylphenol in ethanolic solution treated with ferric nitrate nonahydrate (1 equiv.) and heated briefly for 30 sec. afforded an 83% yield of 4-methyl-2-nitrophenol. Under similar conditions 4-chlorophenol gave 4-chloro-2-nitrophenol (88%), 4-bromophenol gave 4-bromo-2-nitrophenol (64%) and 2-chlorophenol, a mixture of 2-chloro-4-nitrophenol (56%) and 2-chk ro-6-nitrophenol (35%). Aluminium, chromium and copper(ll) nitrates were also used (ref.63). 

2-Nitroestrone has been obtained in 79% yield by the addition of estrone to molar proportions of benzeneselenyl chloride and silver nitrate in acetonitrile followed by reaction with stirring for 3 hours at ambient temperature (ref.64). 

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Non-aromatic precursors have been employed for the synthesis of nitrophenols since the application of nitromatonaldehyde in early work, by for example its reaction with 3-pentanone to give 4-nitro-2,6-dimethyl phenol in 94% yield (ref.68). 

Anderson, James S. Brown, Keith C. Synthesis of nitrophenols. Synth. Commun. 1983,13, 233-236. 

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