Sulfuric Acid → 6-Chloro-5-(4-chlorophenyl)pyridin-2-amine

HRID 1995623Notes

Reaction equation

HRID 1995623 reaction equation
[NH2:1][C:2]1[C:7](C(O)=O)=[CH:6][C:5]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[C:4]([Cl:18])[N:3]=1.OS(O)(=O)=O.[OH-].[Na+]>O>[Cl:18][C:4]1[N:3]=[C:2]([NH2:1])[CH:7]=[CH:6][C:5]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 135028582-Amino-6-chloro-5-(4-chlorophenyl)pyridine-3-carboxylic acid

Product 1

HCID 135028596-Chloro-5-(4-chlorophenyl)pyridin-2-amineYield 7.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

2-Amino-6-chloro-5-(4-chlorophenyl)-3-pyridinecarboxylic acid (9 grams), 300 ml H2SO4, and 90 ml water were heated in an oil bath at 220°-230° C. for 1 hour. The reaction mixture was diluted to 2 liters, cooled, and neutralized with 50% NaOH. A gum-like solid formed which was only partially removed by filtration. The filtrate was then extracted four times with 800-1000 ml portions of CH2Cl2 taking care not to remove any of gum-like solid. The combined CH2Cl2 layers were dried over MgSO4. The filtered solid was dissolved in ethyl acetate and then the aqueous-solid mixture was extracted with the same solvent. TLC of this extract showed the desired product and an impurity. Next the CH2Cl2 extracts were filtered and stripped to give about 0.6 gram of the desired product, m.p. 178°-182° C. The ethyl acetate extract was similarly treated to give a solid residue. Trituration of this solid with hot CH2Cl2 followed by filtration and stripping gave about 0.8 gram of the desired product, m.p. 179°-183° C.

Workup

  1. additionThe reaction mixture was diluted to 2 liters
  2. temperaturecooled
  3. customA gum-like solid formed which
  4. customwas only partially removed by filtration
  5. extractionThe filtrate was then extracted four times with 800-1000 ml portions of CH2Cl2 taking care not
  6. customto remove any of gum-like solid
  7. dry with materialThe combined CH2Cl2 layers were dried over MgSO4
  8. dissolutionThe filtered solid was dissolved in ethyl acetate
  9. extractionthe aqueous-solid mixture was extracted with the same solvent
  10. filtrationNext the CH2Cl2 extracts were filtered

Sources & evidence

ORD record
ord-e0351c59260e44909ef677bf452a2673
Source dataset
uspto-grants-1983_09
Patent number
US04405552

Reaction notes

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