Hydrochloric Acid → 4-Amino-2,3,6-trimethylphenol

HRID 1638749Notes

Reaction equation

HRID 1638749 reaction equation
S(O)(=O)(C1C=CC([NH2:9])=CC=1)=O.C([O-])([O-])=O.[Na+].[Na+].N([O-])=O.[Na+].Cl.[OH-].[Na+].[CH3:25][C:26]1[C:31]([CH3:32])=[CH:30][CH:29]=[C:28]([CH3:33])[C:27]=1[OH:34].[O-]S(S([O-])=O)=O.[Na+].[Na+]>O.C(OCC)(=O)C>[NH2:9][C:30]1[CH:29]=[C:28]([CH3:33])[C:27]([OH:34])=[C:26]([CH3:25])[C:31]=1[CH3:32]

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 8479Sulfanilic acidHCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 170162,3,6-TrimethylphenolHCID 24489Sodium Dithionite2×HCID 23668193Sodium Nitrite

Product 1

HCID 826664-Amino-2,3,6-trimethylphenol

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
15 °C

Procedure

Into a solution of sulfanilic acid (13.0 grams, 68 mmol) in water (68 milliliters) contained in a 250 milliliter round bottom flask equipped with a magnetic stirrer, internal thermometer and ice bath at 15° C. was added solid Na2CO3 (3.69 grams, 34 mmol) followed by a solution of NaNO2 (5.1 grams, 74 mmol) in water (14 milliliters). The latter addition caused a color change from milky-white to orange. A separate 500 milliliter three-necked flask equipped with a magnetic stirrer, internal thermometer and ice bath was charged with concentrated hydrochloric acid (12 milliliters), ice (68 grams) and the solution of the diazonium salt prepared above. This mixture was stirred at 15° C. for 45 minutes. Meanwhile a third flask (1 L) equipped with an internal thermometer, nitrogen inlet, condenser, addition funnel and mechanical stirrer was charged with water (68 milliliters), NaOH (14.96 grams, 318 mmol) and 2,3,6-trimethylphenol (9.30 grams, 68 mmol). This mixture was cooled to 0° C. by means of an ice-salt mixture and the diazonium salt - hydrochloric acid mixture prepared above was added dropwise while maintaining the temperature below 5° C. Upon completion of the diazonium salt addition the reaction mixture was warmed to 52° C. and solid Na2S2O4 (3.13 grams, 18 mmol) was added. Stirring was continued and the mixture heated to 80° C. whereupon additional Na2S2O4 (28.2 grams, 162 mmol) was added in three equal portions (9.4 grams each) at 5 minute intervals. The mixture was heated at 80° C. under nitrogen for 20 minutes, cooled to room temperature and filtered to afford the crude product as a yellow solid. The solid was dissolved in ethyl acetate (300 milliliters) and washed with water. The organic layer was dried over Na2SO4 and concentrated under reduced pressure to afford 4-amino-2,3,6-trimethylphenol in quantitative yield which was used successfully in subsequent reactions without further purification. H'-NMR (CDCl3) 6.30 (S, 1H), 2.11 (S, 9H).

Workup

  1. customequipped with a magnetic stirrer
  2. additionThe latter addition
  3. customA separate 500 milliliter three-necked flask equipped with a magnetic stirrer
  4. customMeanwhile a third flask (1 L) equipped with an internal thermometer, nitrogen inlet, condenser, addition funnel and mechanical stirrer
  5. additionabove was added dropwise
  6. temperaturewhile maintaining the temperature below 5° C
  7. temperaturewas warmed to 52° C.
  8. stirringStirring
  9. additionwas added in three equal portions (9.4 grams each) at 5 minute intervals
  10. temperatureThe mixture was heated at 80° C. under nitrogen for 20 minutes
  11. temperaturecooled to room temperature
  12. filtrationfiltered
  13. customto afford the crude product as a yellow solid
  14. washwashed with water
  15. dry with materialThe organic layer was dried over Na2SO4
  16. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a4415ca405c4438e82a01b5cf4fcaebb
Source dataset
uspto-grants-1989_11
Patent number
US04880838

Reaction notes

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