Preparation of 3-amino-5-bromo-2-nitropyridine_Industrial additives

Preparation background and overview of 3-amino-5-bromo-2-nitropyridine

3-Amino-5-bromo-2-nitropyridine is an organic intermediate, which can be prepared from 3-amino-5-bromopyridine as raw material, first protecting the amino group, then nitrating and deprotecting it.

Preparation of 3-amino-5-bromo-2-nitropyridine

Preparation step 1 of 3-amino-5-bromo-2-nitropyridine: Preparation of 3-propoxycarbonylamino-5-bromopyridine (1)

Weigh 3-amino-5-bromopyridine (5.0g, 28.9mmol) into a 100mL flask, add 20mL tetrahydrofuran to dissolve, and add sodium bicarbonate (7.3g, 86.9mmol). Propyl chloroformate (911 triglyceride carbonate. 3 mL, 86.9 mmol) was added dropwise to the flask. After stirring for 15 minutes, the tetrahydrofuran was evaporated, 30 mL of water was added to the flask, ethyl acetate (3×20 mL) was added for extraction three times, dried, and the solvent was evaporated to dryness to obtain the crude product of 1. Without separation and purification, proceed directly to the next step of nitration reaction.

Step 2: Preparation of 2-nitro-3-propoxycarbonylamino-5-bromopyridine (2)

Add 15 mL of concentrated sulfuric acid to the flask containing Intermediate 1, place the flask in an ice water bath, and drop 5 mL of fuming nitric acid into the flask. The flask was brought to room temperature and stirred for 12 hours. Slowly add the reaction solution to the crushed ice in batches, and add solid potassium hydroxide to the ice water until the solution becomes alkaline. Extract three times with ethyl acetate, add anhydrous Na₂SO₄ to dry, filter with suction, and concentrate under reduced pressure. Column chromatography of ethyl acetate: petroleum ether = 1:20 gave yellow solid 2. Yield: 81%, melting point: 74-76°C, ¹H NMR (MHz, DMSO-d6, ppm) δ: 10.11 (s, 1H), 8.48-8.46 (m, 2H), 4.08(t,2H,J＝6.7Hz,CH2), 1.64(sext,2H,J＝7.3Hz,CH2), 0.93(t,3H,J＝7.4Hz,CH3).¹³ C-NMR (100MHz, DMSO-d6, ppm) δ: 153.76 (C＝O), 148.01, 143.82, 136.15, 129.79, 124.92, 67.64 (OCH2), 22.15 (CH2), 10.56 (CH3).

Preparation step three of 3-amino-5-bromo-2-nitropyridine: Preparation of 3-amino-5-bromo-2-nitropyridine (3)

Weigh KOH (0.55g, 9.8mmol) into the flask, add 8mL of water to dissolve, add 1.5mL of absolute ethanol to the flask, and add 2 (1.0g, 3.3mmol). Stir for 1 hour at 90°C, then continue stirring for 1 hour after cooling to room temperature. After the reaction is completed, add 20 mL of water to the flask and filter. The filter cake was dried in a vacuum drying oven at 45°C for 24 hours to obtain yellow solid 3, yield: 94%, melting point: 183-185°C, ¹H NMR (MHz, DMSO-d6, ppm) δ :7.84(d,J＝2.0Hz,1H,pyridine-H),7.77(d,1H,J＝2.0Hz,pyridine-H),7.45(s,2H,NH2).¹³ C-NMR (100MHz, DMSO-d6, ppm) δ: 142.53, 138.93, 136.06, 130.27, 126.43.

References

[1] [Chinese invention, Chinese invention authorization] CN201510227645.3 A diarylpyridine derivative and its preparation method and application