Chloroform → 3-Methoxy-2-methylbenzohydrazide

HRID 1184309Notes

Reaction equation

HRID 1184309 reaction equation
[OH2:1].[NH2:2][NH2:3].[C:4]([O-:7])([O-])=O.[K+].[K+].CO[C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=1)[C:15](Cl)=O.[CH:21](Cl)(Cl)Cl>O.C(Cl)Cl.CCCCC.CCCCCCC>[CH3:21][O:1][C:13]1[C:14]([CH3:15])=[C:18]([CH:19]=[CH:20][CH:12]=1)[C:4]([NH:2][NH2:3])=[O:7]

Participants

9

Reactant 4

HCID 6212ChloroformHCID 11430Potassium CarbonateHCID 24654Hydrazine hydrate (1:1)HCID 74374m-Anisoyl chloride

Product 1

HCID 450912733-Methoxy-2-methylbenzohydrazide

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×HCID 8003PentaneSolventHCID 8900HeptaneSolvent

Procedure

To a 500 mL, 3-neck flask equipped with a magnetic stirrer, and chilled in an ice water bath, were added 25 mL of CH2Cl2 (significantly greater quantities can be used) and 22.5 g (450 mmol) of hydrazine hydrate, followed by a solution of 31.5 g of K2CO3 dissolved in 60 mL of water. Over a period of 30 minutes, a solution of 31 g (168 mmol) of 2-methyl, 3-methoxybenzoyl chloride dissolved in 50 mL of CH2Cl2 was added, while keeping the temperature below 5° C. The reaction mixture was allowed to warn to room temperature and then stirred for an additional 2 hours. Water (100 mL) and chloroform (150 μL) were added, the mixture was shaken in a separatory funnel, and an inorganic precipitate was filtered off. The organic layer was dried over MgSO4 and the solvent removed in vacuo to leave 30 g of crude product hydrazide. This material was slurried with heptane for 4 hours (pentane slurry gives comparable results). Filtration and residual solvent evaporation yielded 13 g of 3-methoxy-2-methyl-benzoic acid hydrazide, containing ca. 10% of diacylated material. The product could be further purified by precipitation with hot CHCl3/hexane. 1H NMR (300 MHz, CDCl3) δ (ppm): 7.2 (t, 1H), 6.95 (br s, 1H), 6.9 (m, 2H), 4.15 (br s, 2H), 3.84 (s, 3H), 2.27 (s, 3H).

Workup

  1. customTo a 500 mL, 3-neck flask equipped with a magnetic stirrer
  2. temperaturechilled in an ice water bath
  3. additionwas added
  4. customthe temperature below 5° C
  5. customto warn to room temperature
  6. stirringthe mixture was shaken in a separatory funnel
  7. filtrationan inorganic precipitate was filtered off
  8. dry with materialThe organic layer was dried over MgSO4
  9. customthe solvent removed in vacuo
  10. customto leave 30 g of crude product hydrazide
  11. filtrationFiltration and residual solvent evaporation

Sources & evidence

ORD record
ord-a6a78e001eae450a9f46e9f74879b835
Source dataset
uspto-grants-2014_03
Patent number
US08669072B2

Reaction notes

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