Urea → 2-Chloro-4-hydroxybenzoic acid

HRID 1166713Notes

Reaction equation

HRID 1166713 reaction equation
N[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([Cl:11])[CH:3]=1.N([O-])=[O:13].[Na+].NC(N)=O>OS(O)(=O)=O>[Cl:11][C:4]1[CH:3]=[C:2]([OH:13])[CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=[O:7]

Participants

5

Reactant 3

HCID 1176UreaHCID 171544-Amino-2-chlorobenzoic acidHCID 23668193Sodium Nitrite

Product 1

HCID 918212-Chloro-4-hydroxybenzoic acid

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Conditions

Temperature
90 °C

Procedure

4-amino-2-chlorobenzoic acid (10 g, 58 mmol) was dissolved in H2SO4 (12 N, 120 mL) with heating. After cooling the solution in an ice-bath aqueous NaNO2 (2.5 M, 25 mL) was added dropwise such that the internal temperature remained at 5° C. Urea was added to the mixture for after stirring for 15 minutes to destroy excess NaNO2 (monitored by starch iodine test). CuSO4 (100-200 mg) was added and the mixture was heated to 90° C. until evolution of gas stopped. After cooling, the mixture was extracted with ethyl ether (3×). The combined organic fractions were extracted with 3N NaOH (3×). The combined aqueous layer was acidified with conc. HCl and the product was extracted with ethyl ether (3×). The organic fractions were washed with water, brine, and dried over MgSO4. The crude product was introduced into a silica gel column and eluted with ethyl acetate/hexane (1/1) to afford 2-chloro-4-hydroxybenzoic acid.

Workup

  1. temperaturewith heating
  2. additionwas added dropwise such that the internal temperature
  3. customremained at 5° C
  4. customto destroy excess NaNO2 (monitored by starch iodine test)
  5. additionCuSO4 (100-200 mg) was added
  6. temperatureAfter cooling
  7. extractionthe mixture was extracted with ethyl ether (3×)
  8. extractionThe combined organic fractions were extracted with 3N NaOH (3×)
  9. extractionthe product was extracted with ethyl ether (3×)
  10. washThe organic fractions were washed with water, brine
  11. dry with materialdried over MgSO4
  12. additionThe crude product was introduced into a silica gel column
  13. washeluted with ethyl acetate/hexane (1/1)

Sources & evidence

ORD record
ord-5c6fdb3d70df4da99b0b231defe889bd
Source dataset
uspto-grants-2003_09
Patent number
US06613942B1

Reaction notes

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