4-Amino-3-nitrophenol

4-Amino-3-nitrophenol can be prepared from p-aminophenol through a four-step reaction.

1. Synthesis of ethyl 3-nitro-4-acetamidophenol
In a 250mL three-necked flask equipped with a thermometer and a stirrer, add 21.0g of p-aminophenol, 60.0mL of acetic anhydride and 16.0mL of glacial acetic acid, heat to 128℃, and reflux. At this point, the reaction solution is a reddish-brown liquid. After 2 hours, the reaction solution was cooled to 25°C (a large amount of light pink solid precipitated in the reaction solution), and then 10.0 mL of fuming nitric acid (10 drops/min) was slowly added dropwise, maintaining the temperature at 25–26°C. Stirring was performed for 1.5 hours under strong acid conditions, resulting in the precipitation of numerous yellow crystals. The reaction solution was then poured into a large amount of ice water, immediately precipitating a large amount of yellow crystals. The crystals were washed 2–3 times with water until neutral, filtered, and the filter cake was dried. 33.9 g of yellow 3-nitro-4-acetamidophenol ethyl ester was obtained, with a yield of 73.9%. Melting point: 146–148°C.
2. Synthesis of 4-Amino-3-nitrophenol
5.4 g of 3-nitro-4-acetamidophenol ethyl ester, 20 mL of anhydrous ethanol, and 30.0 mL of 3 mol/L sodium hydroxide solution were added to a 150 mL three-necked flask equipped with a thermometer and stirrer. The mixture was heated to 60°C and stirred at this temperature for 1 hour. After the reaction was complete, the ethanol was evaporated under reduced pressure, and the reaction solution was cooled to below 10°C. The pH of the reaction solution was then adjusted to 3–4 using a hydrochloric acid solution [m(36%–38% concentrated hydrochloric acid):m(water) = 1:1]. Red crystals precipitated. The crystals were filtered, and the filter cake was dried to obtain 3.3 g of brownish-red 4-Amino-3-nitrophenol. The yield was 93.9%, and the melting point was 149–151°C.

Dark red powder

4-Amino-3-nitrophenol is an aminonitrophenol isomer used in hair dyes, potent human skin sensitizers and other cosmetic products with very low levels of mutagenic activity.

4-Amino-3-nitrophenol was used in the synthesis of benzimidazole based Factor Xa (trypsin-like serine protease) inhibitors and 4-(4-amino-3-nitrophenoxy)phthalonitrile. It was also employed as matrix during visible matrix-assisted laser desorption/ionization mass spectrometry.

This hair dye used for semipermanent colors seems to be a rare sensitizer.