3,5,6-TRICHLORO-4-HYDRAZINO-PYRIDINE-2-CARBOXYLIC ACID synthesis

Yield:32889-74-0 83%

Reaction Conditions:

with sodium hydroxide;hydrazine in water; for 1.66667 h;Reflux;

Steps:

8D.A

To a reaction flask containing 200 mL of boiling water was added 26.1 g (0.1 mol) of tetrapicolinic acid, 4.1 g (0.103 mol) of sodium hydroxide previously dissolved in 25 mL of water and 3.47g (0.105mol) of anhydrous hydrazine. The reaction mixture was stirred under reflux for 30 min. An additional 4.1g (0.103mol) of sodium hydroxide in 25 mL of water was slowly added to the reaction mixture over a 25 minute period and the mixture refluxed for 45 min. The reaction mixture was cooled to room temperature and 25 mL of 5N HCl was added. The solid 3,5,6- trichloro-4-hydrazinopicolinic acid (as the monohydrate) which precipitated was recovered by filtration in a yield of 22.9 g (83%). Mp:166"-168°C. [00371] To a mixture (clear solution) of 3,5,6-tricWc?ro-4-hydrazinopicolinic acid (22.9 g, 78 mmol), 115 mL of2Q% sodium hydroxide and 15O mL of water was added 10O mL of 10-13% sodium hypochlorite solution at 3O°C. Immediate gas evolution was noted which ceased after about 3 min. Five minutes after the addition of the sodium hypochlorite solution, the reaction mixture was acidified to a pH of about 2 with concentrated hydrochloric acid (15OmL). The mixture was extracted with methylene chloride. The methylene chloride was removed from the extract by evaporation leaving the crude 3,5,6-trichloropicolinic acid. The crude product was dissolved in IN NaOH to form a clear solution and cooled to 0 °C and neutralized with 5N HCl with stirring at O°C. The solid was filtered and washed with water to give the pure enough product (15.5 g, 88%). Total yield: 68%. Mp.l47-151°C. [00372] ¹H NMR (DMSO^, 400 MHz): δ 14.31 (brs, 1H, OH, exchangeable with D₂O), 8.60 (s, 1H).

References:

WO2009/89263,2009,A2 Location in patent:Page/Page column 111-112