Ethylenediaminetetraacetic Acid → 5-Acetyl-2-aminobenzenesulfonamide

HRID 496102Notes

Reaction equation

HRID 496102 reaction equation
[CH2:1]([O:3]C=C)[CH3:2].[Li]C(C)(C)C.I[C:12]1[CH:13]=[CH:14][C:15]([NH2:22])=[C:16]([S:18]([NH2:21])(=[O:20])=[O:19])[CH:17]=1.C(N(CC(O)=O)CC(O)=O)CN(CC(O)=O)CC(O)=O.[OH-].[Na+]>C1COCC1.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCCCCC>[C:1]([C:12]1[CH:13]=[CH:14][C:15]([NH2:22])=[C:16]([S:18]([NH2:21])(=[O:20])=[O:19])[CH:17]=1)(=[O:3])[CH3:2]

Participants

10

Reactant 5

HCID 6049Ethylenediaminetetraacetic AcidHCID 8023Ethyl vinyl etherHCID 14798Sodium HydroxideHCID 223240882-Amino-5-iodobenzenesulfonamide2×HCID 178418306HCID 178418306, compound

Product 1

HCID 129523995-Acetyl-2-aminobenzenesulfonamideYield 74%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of ethylvinylether (5.8 ml, 60 mmol) in dry THF (50 ml) at −78° C. was added t-BuLi (1.7 M in pentane, 25 ml, 40 mmol) and the yellow mixture was stirred for 1 h at −78° C. The cooling bath was removed and the mixture was warmed slowly to 0° C. and stirred for another 30 min. The mixture was recooled to −78° C. and a solution of ZnCl2 (2M in THF, 20 ml, 40 mmol) was added slowly and the cooling bath was removed and warmed to 20° C. 5-Iodo-2-aminobenzenesulfonamide (see compound 37) (1.8 g, 6 mmol) and Pd(PPh3)4 (0.2 g, 3 mol %) was added and the mixture was refluxed for 6 h. The THF was evaporated and the residue was boiled in 1 M hydrochloric acid (30 ml) and MeOH (30 ml) for 30 min. EDTA (14.6 g, 50 mmol) was added and made slightly basic (pH=8-9) with 1 M NaOH followed by extraction with EtOAc (3×150 ml), drying (Na2SO4) and evaporation of the solvent gave a brown solid. Trituration with n-hexane gave 0.95 g (74%) of 5-acetyl-2-aminobenzenesulfonamide as off-white powder. The product was further transformed by Method G (using cyclohexanecarboxaldehyde). M.p. 224-226° C. (decomp).

Workup

  1. customThe cooling bath was removed
  2. temperaturethe mixture was warmed slowly to 0° C.
  3. stirringstirred for another 30 min
  4. customwas recooled to −78° C.
  5. customthe cooling bath was removed
  6. temperaturewarmed to 20° C
  7. temperaturethe mixture was refluxed for 6 h
  8. customThe THF was evaporated
  9. waitMeOH (30 ml) for 30 min
  10. extractionfollowed by extraction with EtOAc (3×150 ml)
  11. customdrying
  12. custom(Na2SO4) and evaporation of the solvent
  13. customgave a brown solid

Sources & evidence

ORD record
ord-d882de079fe840589a1adccd40227bc2
Source dataset
uspto-grants-2005_09
Patent number
US06943159B1

Reaction notes

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