Methanol → 4-Methoxy-2,3,5-trimethylpyridine 1-oxide

HRID 463804Notes

Reaction equation

HRID 463804 reaction equation
[CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([CH3:9])=[CH:4][N+:3]=1[O-:10].OS(O)(=O)=O.[N+]([O-])(O)=O.[OH-:20].[Na+].[CH3:22]O>O.C(Cl)Cl>[CH3:1][C:2]1[C:7]([CH3:8])=[C:6]([O:20][CH3:22])[C:5]([CH3:9])=[CH:4][N+:3]=1[O-:10]

Participants

8

Reactant 5

HCID 887MethanolHCID 944Nitric AcidHCID 1118Sulfuric Acid3×HCID 14798Sodium Hydroxide3×HCID 104869072,3,5-Trimethyl-1-oxidopyridin-1-ium

Product 1

HCID 107022374-Methoxy-2,3,5-trimethylpyridine 1-oxide

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
30 °C

Procedure

2,3,5-trimethyl-pyridine-N-oxide (1457 g, 10 moles) was dissolved in conc. H2SO4 (1200 ml, 22.08 moles) in a 50 liters reaction vessel. A nitration solution (1750 ml, 32.2 moles conc. H2SO4 and 2065 ml, 29.84 moles 65% HNO3) was added at 90° C. during 1 hour. The solution was stirred at 90° for 1.5 hours and thereafter cooled to 30° C. The pH of the reaction mixture was then adjusted by adding 10M NaOH (11.65 liters, 116.5 moles) during cooling with water so that the temperature was kept below 40° C. The NaOH was added during about 2 hours. Thereafter CH2Cl2 (25 liters) was added and the mixture stirred vigorously for 30 minutes. The phases formed were separated and the CH2Cl2 -phase was transferred to a 100 liters reaction vessel. The water phase was discarded. The methylenechloride was distilled off. To the remainder was added 15 l of toluene which was then distilled off under reduced pressure, followed by another 15 l portion of toluene which was also removed by distillation. 8 liters of methanol was added and the mixture heated to boiling temperature. A solution of NaOH (595 g, 14.9 moles) in CH3OH (16 liters) was added during about 1.5 hours. The reaction mixture obtained was cooled and its pH adjusted to 8 using conc. H2SO4 (250 ml, 4.6 moles). Remaining methanol was distilled off and CH2Cl2 (20 liters) was added to the remainder. The mixture was stirred for about 30 minutes and inorganic salts were filtered off and washed with CH2Cl2. The filtrates obtained were pooled and evaporated, yielding 1287 g of 2,3,5-trimethyl-4-methoxy-pyridine-N-oxide with a purity of 89%. The identity of the reaction product was confirmed with 1H and 13C NMR. 1H-NMR: δ(COCl3) 2.22(s,3H),2.27(s,3H),2.51(s,3H),3.81(s,3H),8.18(s,1H).

Workup

  1. customwas kept below 40° C
  2. stirringthe mixture stirred vigorously for 30 minutes
  3. customThe phases formed
  4. customwere separated
  5. customthe CH2Cl2 -phase was transferred to a 100 liters reaction vessel
  6. distillationThe methylenechloride was distilled off
  7. additionTo the remainder was added 15 l of toluene which
  8. distillationwas then distilled off under reduced pressure
  9. customwas also removed by distillation
  10. addition8 liters of methanol was added
  11. temperaturethe mixture heated
  12. customThe reaction mixture obtained
  13. temperaturewas cooled
  14. distillationRemaining methanol was distilled off
  15. additionCH2Cl2 (20 liters) was added to the remainder
  16. stirringThe mixture was stirred for about 30 minutes
  17. filtrationinorganic salts were filtered off
  18. washwashed with CH2Cl2
  19. customThe filtrates obtained
  20. customevaporated

Sources & evidence

ORD record
ord-eb7da00bfb10404c87dea15c15ddbe50
Source dataset
uspto-grants-1985_10
Patent number
US04544750

Reaction notes

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