Chloroacetyl chloride → n'-(2-Chloroacetyl)benzohydrazide

HRID 877151Notes

Reaction equation

HRID 877151 reaction equation
[C:1]1([C:7]([NH:9][NH2:10])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:11][CH2:12][C:13](Cl)=[O:14].ClCCl.CO.C(=O)(O)[O-].[Na+]>C1COCC1.ClCCl.CO.C(OCC)(=O)C.O>[Cl:11][CH2:12][C:13]([NH:10][NH:9][C:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:8])=[O:14]

Participants

10

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 11955Benzoylhydrazine2×HCID 516892Sodium BicarbonateHCID 21226129Dichloromethane methanol

Product 1

HCID 736972n'-(2-Chloroacetyl)benzohydrazide

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 500 g (3.67 mol) of benzenecarbohydrazide in 3.75 liters of THF was heated at reflux, where the benzenecarbohydrazide went into solution. 497.7 g (4.41 mol) of chloroacetyl chloride, dissolved in 125 ml of THF, were added dropwise to this solution, and the solution was stirred under reflux for 30 min. After the reaction had gone to completion (monitored by TLC, mobile phase dichloromethane/methanol 9:1), 22.5 liters of water and 10 liters of ethyl acetate were added to the reaction mixture, and the pH was adjusted to pH 7 using solid sodium bicarbonate. The aqueous phase was extracted once with 2.5 liters of ethyl acetate. The combined organic phases were dried and the solution was then concentrated to dryness under reduced pressure. The white solid obtained was dissolved in a 1:1 mixture of dichloromethane and methanol and applied to 3 kg of silica gel. The product was chromatographed on two portions of silica gel (in each case 8 kg) initially with 50 liters of dichloromethane/ethyl acetate 7:3 and then with 125 liters of dichloromethane/ethyl acetate 1:1 as mobile phase. Concentration of the product fractions gave 424 g (1.99 mol, 54% of theory) of the title compound as a white solid.

Workup

  1. temperaturewas heated
  2. temperatureat reflux
  3. additionwere added dropwise to this solution
  4. temperatureunder reflux for 30 min
  5. additionwere added to the reaction mixture
  6. extractionThe aqueous phase was extracted once with 2.5 liters of ethyl acetate
  7. customThe combined organic phases were dried
  8. concentrationthe solution was then concentrated to dryness under reduced pressure
  9. customThe white solid obtained
  10. customThe product was chromatographed on two portions of silica gel (in each case 8 kg) initially with 50 liters of dichloromethane/ethyl acetate 7:3

Sources & evidence

ORD record
ord-1ed961f398654f799ee3daf27250b11c
Source dataset
uspto-grants-2015_03
Patent number
US08987256B2

Reaction notes

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