Water → n'-(2-Chloroacetyl)benzohydrazide

HRID 238177Notes

Reaction equation

HRID 238177 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].O.C(=O)(O)[O-].[Na+]>C1COCC1.ClCCl.CO.C(OCC)(=O)C>[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

9

Reactant 4

HCID 962WaterHCID 6577Chloroacetyl chlorideHCID 11955Benzoylhydrazine2×HCID 516892Sodium Bicarbonate

Product 1

HCID 736972n'-(2-Chloroacetyl)benzohydrazide

Reagents, catalysts & solvents 4

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

Procedure

A suspension of 500 g (3.67 mol) of benzenecarbohydrazide in 3.75 liters of THF was heated to reflux, whereupon the benzenecarbohydrazide dissolved. 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 another 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 and the mixture was adjusted to pH 7 with 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. Using two portions of silica gel (8 kg each), the product was chromatographed using initially 50 liters of dichloromethane/ethyl acetate 7:3 and then 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. dissolutiondissolved
  3. additionwere added dropwise to this solution
  4. temperatureunder reflux for another 30 min
  5. additionwere added
  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

Sources & evidence

ORD record
ord-9d3eebb7e45b4c949ba61a5b2dc7c775
Source dataset
uspto-grants-2014_02
Patent number
US08642592B2

Reaction notes

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