1-Methylimidazole → 2-amino-5-(1-methyl-1H-2-imidazolyl)-1-benzenesulfonamide

HRID 496121Notes

Reaction equation

HRID 496121 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[CH:3]1.[Li]CCCC.C([C:14]1[CH:15]=[CH:16][C:17]([NH2:24])=[C:18]([S:20]([NH2:23])(=[O:22])=[O:21])[CH:19]=1)#N.C(N(CC(O)=O)CC(O)=O)CN(CC(O)=O)CC(O)=O.[OH-].[Na+]>C1COCC1.CO.C(Cl)Cl.[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>[NH2:24][C:17]1[CH:16]=[CH:15][C:14]([C:3]2[N:2]([CH3:1])[CH:6]=[CH:5][N:4]=2)=[CH:19][C:18]=1[S:20]([NH2:23])(=[O:21])=[O:22]

Participants

11

Reactant 5

HCID 13901-MethylimidazoleHCID 6049Ethylenediaminetetraacetic AcidHCID 14798Sodium HydroxideHCID 223239942-Amino-5-cyanobenzene-1-sulfonamide2×HCID 178418339Butyllithium

Product 1

HCID 223240062-amino-5-(1-methyl-1H-2-imidazolyl)-1-benzenesulfonamideYield 75.3%

Reagents, catalysts & solvents 5

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-methylimidazole (4.8 ml, 60 mmol) in dry THF (120 ml) at −78° C. was added n-BuLi (2.5 M in hexane, 26 ml, 65 mmol) and the yellow mixture was stirred for 45 min at −78° C. A solution of ZnCl2 (2M in THF, 75 ml, 150 mmol) was added slowly and the cooling bath was removed. The colorless solution was stirred for another 10 min at 0° C. 5-Iodo-2-aminobenzenesulfonamide (see compound 37) (2.1 g, 7 mmol) and Pd(PPh3)4 (0.5 g, 5 mol %) was added and the mixture was refluxed for 6 h. The THF was evaporated and the residue was treated with EDTA (53 g, 0.18 mol) 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 dark oil. Flash-chromatography with 5% MeOH in CH2Cl2 as eluent gave 1.33 g (75%) of 2-amino-5-(1-methyl-1H-2-imidazolyl)-1-benzenesulfonamide as colorless crystals. The product was further transformed by Method G (using cyclohexanecarboxaldehyde). M.p. >250° C. (decomp).

Workup

  1. customthe cooling bath was removed
  2. stirringThe colorless solution was stirred for another 10 min at 0° C
  3. temperaturethe mixture was refluxed for 6 h
  4. customThe THF was evaporated
  5. extractionfollowed by extraction with EtOAc (3×150 ml)
  6. customdrying
  7. custom(Na2SO4) and evaporation of the solvent
  8. customgave a dark oil

Sources & evidence

ORD record
ord-2d0c3e4cea634012a7431af3dc36d349
Source dataset
uspto-grants-2005_09
Patent number
US06943159B1

Reaction notes

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