Synthesis
The general procedure for the synthesis of 3,5-dimethyl-4-nitrophenol from 3,5-dimethylphenol was as follows: 3,5-dimethylphenol (50 g) was dissolved in 200 mL of methanesulfonic acid (MES03H) and the solution was cooled to 0 °C. One equivalent (34.8 g) of sodium nitrate (NaNO3) was added in batches at 0°C. After 18 hours of reaction, the reaction mixture was poured into 4 L of ice water under vigorous stirring. The upper aqueous phase was decanted. The residue was dissolved in 400 mL of ethyl acetate (EtOAc). The ethyl acetate extract was washed with saturated aqueous sodium bicarbonate (NaHCO3) (2 x 200 mL) and subsequently dried with saturated saline and anhydrous sodium sulfate (Na2SO4). Finally, purification was carried out on a silica gel column using a solvent mixture of ethyl acetate and n-heptane (4:1). The intermediate 3,5-dimethyl-4-nitrophenol 7.86 g was obtained in 11% yield.
References
[1] Patent: US6337423, 2002, B1. Location in patent: Example 4, 22
[2] Patent: WO2005/28479, 2005, A2. Location in patent: Page/Page column 54-55
[3] Journal of the American Chemical Society, 1977, vol. 99, # 15, p. 5146 - 5151
[4] Patent: US6462034, 2002, B1
