Nitric Acid → 3-(3-chloro-4-nitro-1H-pyrazol-1-yl)pyridine

HRID 1484595Notes

Reaction equation

HRID 1484595 reaction equation
[Cl:1][C:2]1[CH:6]=[CH:5][N:4]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)[N:3]=1.S(=O)(=O)(O)O.[N+:18]([O-])([OH:20])=[O:19].S(=O)(=O)(O)O.[N+]([O-])(O)=O.[OH-].[Na+]>O>[Cl:1][C:2]1[C:6]([N+:18]([O-:20])=[O:19])=[CH:5][N:4]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)[N:3]=1

Participants

7

Reactant 5

HCID 944Nitric AcidHCID 1118Sulfuric Acid2×HCID 14798Sodium HydroxideHCID 674995403-(3-chloro-1H-pyrazol-1-yl)pyridineHCID 71777668Sulfuric acid, mixt. with nitric acid

Product 1

HCID 675001483-(3-chloro-4-nitro-1H-pyrazol-1-yl)pyridine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
5 °C

Procedure

To a 100 mL, round bottom flask was charged 3-(3-chloro-1H-pyrazol-1-yl)pyridine (2.00 g, 11.1 mmol) and concentrated sulfuric acid (4 mL). This suspension was cooled to 5° C. and 2:1 concentrated nitric acid/sulfuric acid (3 mL, prepared by adding the concentrated sulfuric acid to a stirring and cooling solution of the nitric acid) was added dropwise at a rate such that the internal temperature was maintained <15° C. The reaction was allowed to warm to 20° C. and stirred for 18 hours. A sample of the reaction mixture was carefully diluted into water, basified with sodium hydroxide (50 wt % in water) and extracted with ethyl acetate. Analysis of the organic layer indicated that the reaction was essentially complete. The reaction mixture was carefully added to ice cold water (100 mL) at <20° C. It was basified with sodium hydroxide (50 wt % in water) at <20° C. The resulting light yellow suspension was stirred for 2 hours and filtered. The filter cake was rinsed with water (3×20 mL) and dried to afford an off-white solid (2.5 g, quantitative): mp 141-143° C.; 1H NMR (400 MHz, DMSO-d6) δ 9.86 (s, 1H), 9.23-9.06 (m, 1H), 8.75-8.60 (m, 1H), 8.33 (ddd, J=8.4, 2.8, 1.4 Hz, 1H), 7.64 (ddd, J=8.5, 4.7, 0.7 Hz, 1H); 13C NMR (101 MHz, DMSO-d6) δ 149.49, 140.75, 136.02, 134.43, 132.14, 131.76, 127.22, 124.31; EIMS m/z 224 ([M]+).

Workup

  1. additionwas added dropwise at a rate such that the internal temperature
  2. temperaturewas maintained <15° C
  3. temperatureto warm to 20° C.
  4. extractionextracted with ethyl acetate
  5. additionThe reaction mixture was carefully added to ice cold water (100 mL) at <20° C
  6. customwas basified with sodium hydroxide (50 wt % in water) at <20° C
  7. stirringThe resulting light yellow suspension was stirred for 2 hours
  8. filtrationfiltered
  9. washThe filter cake was rinsed with water (3×20 mL)
  10. customdried
  11. customto afford an off-white solid (2.5 g, quantitative)

Sources & evidence

ORD record
ord-f354d2ff37ce4b9d8c3848c3c3d1d036
Source dataset
uspto-grants-2016_08
Patent number
US09422265B2

Reaction notes

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