Sulfuric Acid → 8-Chloro-5-fluoroquinoline

HRID 2241969Notes

Reaction equation

HRID 2241969 reaction equation
[Cl:1][C:2]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:3]=1[NH2:4].[Na+].[N+]([C:14]1[CH:15]=C(S([O-])(=O)=O)C=C[CH:19]=1)([O-])=O.S(=O)(=O)(O)O>OCC(CO)O>[F:9][C:6]1[CH:7]=[CH:8][C:2]([Cl:1])=[C:3]2[C:5]=1[CH:19]=[CH:14][CH:15]=[N:4]2

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 31389Sodium 3-nitrobenzenesulfonateHCID 27365092-Chloro-5-fluoroaniline

Product 1

HCID 534359938-Chloro-5-fluoroquinolineYield 59.3%

Reagents, catalysts & solvents 1

HCID 753GlycerolSolvent

Conditions

Temperature
140 °C

Procedure

To a mixture of (5.0 g) 2-chloro-5-fluoroaniline (commercially available, 6.0 g), glycerol (6.0 g) and m-nitrobenzene sulfonic acid sodium salt (11.0 g), was added 20 ml of 70% sulfuric acid dropwise. The reaction temperature was raised to 140° C. for 2 hr. The mixture was then cooled, poured on ice water and filtered through celite. The filtrate was neutralized with NaOH and extracted with CH2Cl2. The combined organic layers were dried over anhydrous MgSO4 and concentrated on a rotary evaporator. The crude product was purified by flash chromatography on silica gel using 100% CH2Cl2 to give 3.7 g of the desired product of a yellow solid; MP=74-76° C.; MS (ES) m/z (relative intensity): 182 (M+H)+ (100).

Workup

  1. temperatureThe mixture was then cooled
  2. additionpoured on ice water
  3. filtrationfiltered through celite
  4. extractionextracted with CH2Cl2
  5. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  6. concentrationconcentrated on a rotary evaporator
  7. customThe crude product was purified by flash chromatography on silica gel using 100% CH2Cl2

Sources & evidence

ORD record
ord-6eafdeb0a57846109c7d7a139cc8ae00
Source dataset
uspto-grants-2010_03
Patent number
US07671056B2

Reaction notes

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