Reaction #1050100

Reaction equation

2,3-dimethyl-4-monomethylamino-1-phenyl-3-pyrazolin5-one

4-formylamino-2-methyl1-phenyl-3-pyrazolin-5-one

CH3CN

aminopyrine

4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one

HCl

4-dimethylamino-3hydroxymethyl-2-methyl-1-phenyl-3-pyrazolin-5-one

4formylamino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one

2,3-dimethyl-4hydroxyamino-1-phenyl-3-pyrazolin-5-one

4-formylamino-3-hydroxymethyl-2methyl-1-phenyl-3-pyrazolin-5-one

→

Aminopyrine hydrochloride

Solvents

ether

H2O

Conditions

Workup

1. 1
   Otherlodosobenzene (1650 mg, 7.5 mmol, prepared
2. 2
   workup.ADDITION, 43:60-61 (1963)) was added
3. 3
   workup.ADDITIONTwo hr after the last addition of the oxidant
4. 4
   Otherthe solution was evaporated under reduced pressure at 50° C
5. 5
   workup.DISSOLUTIONThe residue was dissolved in 20 ml of aqueous Na2CO3 solution
6. 6
   Extractionthe solution was extracted with CH2Cl2 (3×50 ml)
7. 7
   DryingThe organic layer was dried over Na2CO3
8. 8
   Otherevaporated under reduced pressure
9. 9
   OtherThe residue was chromatographed on silica gel
10. 10
    Washeluting with 1:25 methanol
11. 11
    OtherSeven oxidation products were obtained from the eluate (see Scheme 2)

Procedure

Aminopyrine hydrochloride was prepared from the free base (Aldrich) by treatment with HCl in ether. lodosobenzene (1650 mg, 7.5 mmol, prepared according to the method of Saltzman et al., Org. Synth., 43:60-61 (1963)) was added with stirring at room temperature in portions every 30 min to a solution of octachloro-octachloro tetrasulfonato Fe(III) porphyrin (6.2 mg 3.9 μmol) in 50 ml of 80:20 H2O:CH3CN containing 678 mg (3.0 mmol) of aminopyrine. Two hr after the last addition of the oxidant, the solution was evaporated under reduced pressure at 50° C. The residue was dissolved in 20 ml of aqueous Na2CO3 solution, and the solution was extracted with CH2Cl2 (3×50 ml). The organic layer was dried over Na2CO3 and evaporated under reduced pressure. The residue was chromatographed on silica gel, eluting with 1:25 methanol:methylene chloride. Seven oxidation products were obtained from the eluate (see Scheme 2): 2,3-dimethyl-4-monomethylamino-1-phenyl-3-pyrazolin5-one (AP-1); 4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one (AP-2); 4formylamino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one (AP-3); 2,3-dimethyl-4hydroxyamino-1-phenyl-3-pyrazolin-5-one (AP-4); 4-dimethylamino-3hydroxymethyl-2-methyl-1-phenyl-3-pyrazolin-5-one (AP-5); 4-dimethylamino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one-4-oxide (AP-6); and 4-dimethyl-2,3dimethyl-1-(4-hydroxyphenyl)-3-pyrazolin-5-one (AP-7), 4-formylamino-2-methyl1-phenyl-3-pyrazolin-5-one (AP-8), and 4-formylamino-3-hydroxymethyl-2methyl-1-phenyl-3-pyrazolin-5-one (AP-9).

Source