Acetic Acid → HCID 178526878, compound

HRID 1937050Notes

Reaction equation

HRID 1937050 reaction equation
[OH:1][C:2]1[C:7](C(O)=O)=[CH:6][N:5]=[C:4]([OH:11])[CH:3]=1.P(=O)(O)(O)O.C(O)(=O)C.[N+:21]([O-])([OH:23])=[O:22].O>>[OH:11][C:4]1[C:3]([N+:21]([O-:23])=[O:22])=[C:2]([OH:1])[CH:7]=[CH:6][N:5]=1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 944Nitric AcidHCID 962WaterHCID 1004Phosphoric AcidHCID 178524769HCID 178524769, compound2×

Product 1

HCID 178526878HCID 178526878, compoundYield 60%

Conditions

Temperature
90 °C

Procedure

A 3-neck 22 L flask equipped with a temperature probe with a chart recorder, mechanical stirrer, a Dean-Stark apparatus and a reflux condenser is charged with 4,6-dihydroxy nicotinic acid (88 %, 2.0 Kg, 12.81 mol), phosphoric acid (85%, 6 L, 103.15 mol). The off gases from the condenser are scrubbed by bubbling into 50% aqueous NaOH. The suspension is heated until a sufficient amount of water has been removed (about 1.2 L) , i.e., dehydration of the phosphoric acid. Without the dehydration of the phosphoric acid, the carboxylation does not occur. For the internal temperature to reach 210° C.±5° C, a mantle temperature of 290° C is applied over an elapsed time of 3.5 hours. After being stirred for 4-5 hours at that temperature, the disappearance of the starting material is confirmed by HPLC. The reaction mixture is then allowed to cool down to a temperature of less than 100° C., at which point acetic acid (6 L, 104.81 mol) is added and the temperature is maintained at 90° C. To this mixture is added nitric acid (485 mL, 12.11 mol) at a constant rate (5-6 mL/minute) until HPLC shows no more 4,6-dihydroxy nicotinic acid present. Water (6 L, 333.3 mol) is then added to the reaction and heating is stopped. A yellow solid starts appearing at a temperature of less than 80° C. and is allowed to precipitate with stirring overnight. Filtration in a scintered glass funnel (course porosity) yields a yellow solid which is then washed with 2.5 L of isopropyl alcohol. The resulting cake is air-dried for 48 hours and then put in a drying oven under vacuum (20 in. Hg with a air bleed) at 50° C. for 3 days. 2,4-dihydroxy-3-nitropyridine (1.050 Kg) is obtained in 60% yield.

Workup

  1. customA 3-neck 22 L flask equipped with a temperature probe with a chart recorder, mechanical stirrer
  2. customby bubbling into 50% aqueous NaOH
  3. temperatureThe suspension is heated until a sufficient amount of water
  4. customhas been removed (about 1.2 L) , i.e., dehydration of the phosphoric acid
  5. customto reach 210° C.±5° C
  6. customa mantle temperature of 290° C
  7. customis applied over an elapsed time of 3.5 hours
  8. additionis added
  9. temperatureheating
  10. customappearing at a temperature of less than 80° C.
  11. customto precipitate
  12. stirringwith stirring overnight
  13. filtrationFiltration in a scintered glass funnel (course porosity)
  14. customyields a yellow solid which
  15. washis then washed with 2.5 L of isopropyl alcohol
  16. customThe resulting cake is air-dried for 48 hours
  17. customput in a drying oven under vacuum
  18. waitHg with a air bleed) at 50° C. for 3 days

Sources & evidence

ORD record
ord-c80ad23c6efb47909cbfcc7b34dd835b
Source dataset
uspto-grants-2002_05
Patent number
US06392049B1

Reaction notes

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