Glycerol → Quinoline, 7,8-Difluoro-

HRID 1618911Notes

Reaction equation

HRID 1618911 reaction equation
S(=O)(=O)(O)O.[F:6][C:7]1[C:13]([F:14])=[CH:12][CH:11]=[CH:10][C:8]=1[NH2:9].O[CH2:16][CH:17]([CH2:19]O)O>[I-].[Na+]>[F:14][C:13]1[C:7]([F:6])=[C:8]2[C:10]([CH:16]=[CH:17][CH:19]=[N:9]2)=[CH:11][CH:12]=1

Participants

5

Reactant 3

HCID 753GlycerolHCID 1118Sulfuric AcidHCID 782782,3-Difluoroaniline

Product 1

HCID 3025799Quinoline, 7,8-Difluoro-Yield 91%

Reagents, catalysts & solvents 1

HCID 5238Sodium IodideCatalyst

Conditions

Temperature
0 °C

Procedure

In a 3 L eggplant-shaped flask containing a stir bar, 80% sulfuric acid (607.7 g, 49.57 mol) was introduced and cooled to 0° C., and then 2,3-difluoroaniline (160.0 g, 1.24 mol) was slowly added. After the addition, the mixture was stirred for 1 hour at room temperature, sodium iodide (1.85 g, 12.3 mmol) was further added thereto, and then the mixture was heated in an oil bath until the temperature thereof reached 150° C. (temperature of the bath). When it reached this temperature, glycerin (125.5 g, 1.36 mol) was added dropwise over a period of one hour, and the mixture was stirred for 1 hour at 150° C. The temperature of the bath was further elevated to 180° C., and the water was evaporated over a period of 2 hours using a distillation apparatus. After confirming that the starting material had disappeared, the mixture was neutralized using 10N aqueous sodium hydroxide while cooling with an ice-water bath (the inner temperature is 60 to 70° C.). After the neutralization, before the inner temperature returned to room temperature, the resultant was subjected to extraction with ethyl acetate, and the extract was dried with magnesium sulfate, filtered, and concentrated. The thus obtained crude product was purified by silica gel column chromatography (normal hexane:ethyl acetate) to obtain 185.5 g of 7,8-difluoroquinoline (91%) as a hazel solid.

Workup

  1. additionIn a 3 L eggplant-shaped flask containing a stir bar
  2. additionAfter the addition
  3. temperaturethe mixture was heated in an oil bath until the temperature
  4. customthereof reached 150° C.
  5. additionwas added dropwise over a period of one hour
  6. stirringthe mixture was stirred for 1 hour at 150° C
  7. customwas further elevated to 180° C.
  8. customthe water was evaporated over a period of 2 hours
  9. temperaturewhile cooling with an ice-water bath (the inner temperature
  10. customis 60 to 70° C.
  11. customreturned to room temperature
  12. extractionthe resultant was subjected to extraction with ethyl acetate
  13. dry with materialthe extract was dried with magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customThe thus obtained crude product
  17. customwas purified by silica gel column chromatography (normal hexane:ethyl acetate)

Sources & evidence

ORD record
ord-32bc93bfe1f949749a1fad2417db2063
Source dataset
uspto-grants-2014_07
Patent number
US08772200B2

Reaction notes

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