Preparation method of p-nitro-m-phenylenediamine_Kain Industrial Additive

Background and overview^[1]

4-Bromoquinoline-6-carboxylic acid can be used as a pharmaceutical synthesis intermediate. If 4-bromoquinoline-6-carboxylic acid is inhaled, move the patient to fresh air; if there is skin contact, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical attention if you feel unwell; if In case of eye contact, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.

Preparation^[1]

1) In a stirring glass reaction vessel, add 222.0g m-phenylenediamine, add 78g acetic anhydride dropwise, and keep the temperature below 50 degrees. After adding acetic anhydride, add 150 grams of m-phenylenediamine into the solution at a rate of 1g per minute. After adding water, the solution turns off-white to milky white. After stirring for 3-4 hours, a light purple precipitate will form. The precipitate was filtered, washed with cold water and recovered. The recovered wet cake is dried below 80°C. Yields 100-110 grams of m-diacetylanilide. This product has an off-white appearance and a melting point of approximately 190°C. Relative to m-phenylenediamine, 72-80% of theoretical yields were obtained.

2) In a stirred glass reaction vessel, add 29.0g of meta-diacetylanilide to 143g of concentrated sulfuric acid, and keep the temperature below 40°C. During acid addition, once in solution (about 1 hour), place the reaction vessel in an ice-water bath to lower the tank temperature to below 10°C. When 10°C is reached, 30 grams of 70% nitric acid are added dropwise to the solution. The temperature is maintained between 10-20 degrees. After adding nitric acid, continue stirring for 30 minutes. The mixture is then transferred to another container containing 500g. After stirring for one hour, the product was filtered. Dry the bright yellow recovered wet filter cake below 80°C. Obtain 32-34g of 4-nitro-m-diacetanilide with a melting point of about 245°C. Relative to m-diacetylanilide, 90-95% of theoretical yields were obtained.

3) In a stirred glass reaction vessel, add 60g of isopropyl alcohol solution, 120g of water and 40g of concentrated water. Heat the sulfuric acid to 70°C and add 43 grams of 4-nitro-m-diacetylanilide. The mixture was heated to 85°C for 4 hours. After 4 hours, the solution was cooled to 50°C and neutralized to pH 6-7 with 27% ammonium hydroxide. After neutralization, stir for another 30 minutes. The mixture was further cooled to less than 25°C, 150 grams of water was added, and after 1 hour, the product was filtered, and the recovered wet cake was dried at less than 80°C. Obtain 23-25 grams of p-nitro-m-phenylenediamine, with a yellow to orange appearance and a melting point higher than 156°C. Relative to 4-nitro-m-diacetylanilide, 83 to 90% of theoretical yields were obtained.

4) In a stirred glass reaction vessel, add 50g 4-nitro-m-phenylenediamine to 200g isopropanol, while keeping the temperature below 50 degrees, concentrate and add 110.0g sulfuric acid to the mixture until the pH is ± 0.5. After adding the acid, the mixture is heated to 70-75°C. After 3 hours, the batch was cooled to below 30°C and stirred for an additional hour. The product was filtered, washed with water, and dried at a temperature lower than 80°C to obtain 77-80 g of 4-nitro-m-phenylenediamine sulfate as a yellow-brown powder. Relative to 4-nitro-m-phenylenediamine, 94-97% of theoretical yields were obtained.