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

HRID 1482411Notes

Reaction equation

HRID 1482411 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 50 wt % sodium hydroxide 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 50% sodium hydroxide 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 50% sodium hydroxide 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-4208d938f19b47c898821840a4799285
Source dataset
uspto-grants-2016_08
Patent number
US09414594B2

Reaction notes

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