Sulfuric Acid → [2-(4-Chlorophenylsulfanyl)phenyl]-3-methylpiperazine

HRID 856904Notes

Reaction equation

HRID 856904 reaction equation
[CH3:1][CH:2]1[NH:7][CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2N)[CH2:3]1.S(=O)(=O)(O)O.N([O-])=O.[Na+].C([O-])(=O)C.[Na+].[Cl:29][C:30]1[CH:35]=[CH:34][C:33]([SH:36])=[CH:32][CH:31]=1>O.[OH-].[Na+].[Cu].C(OCC)(=O)C>[Cl:29][C:30]1[CH:35]=[CH:34][C:33]([S:36][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:4]2[CH2:5][CH2:6][NH:7][CH:2]([CH3:1])[CH2:3]2)=[CH:32][CH:31]=1

Participants

10

Reactant 5

HCID 1118Sulfuric AcidHCID 7815p-ChlorothiophenolHCID 517045Sodium AcetateHCID 218649222-(3-Methylpiperazin-1-YL)anilineHCID 23668193Sodium Nitrite

Product 1

HCID 21864889[2-(4-Chlorophenylsulfanyl)phenyl]-3-methylpiperazine

Reagents, catalysts & solvents 4

HCID 23978CopperCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
0 °C

Procedure

2-(3-Methylpiperazin-1-yl)phenylamine (0.96 g, 5 mmol) was dissolved in 30 mL water containing sulfuric acid (0.28 mL, 5.2 mmol) and the solution was cooled to 0° C. and sodium nitrite (0.36 g, 5.2 mmol) was added. The reaction was stirred for 30 minutes before the pH of the reaction was adjusted to pH 7 with sodium acetate. The diazonium salt solution was then added dropwise to a solution of 4-chlorothiophenol in a suspension of copper (0.3 g, 5 mmol) in 2 M NaOH (4 mL). After addition, the reaction mixture was heated to 60° C. for 30 minutes before being allowed to cool to room temperature and ethyl acetate (10 mL) was added. The reaction mixture was filtered and the layers were separated. The aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic phases were dried (MgSO4) and volatile solvents evaporated in vacuo. The crude product was purified by flash chromatography using silica gel, eluting with ethyl acetate/methanol/ammonia 96:3:1. The pure product was isolated as a colourless oil. Yield (0.18 g, 11%) 1H NMR (CDCl3, 500 MHz) 1.12 (d, 3H); 2.6–2.72 (br m, 2H); 3.0–3.15 (m, 5H); 6.9 (m, 2H); 7.08 (d, 1H); 7.15 (m, 1H); 7.25–7.35 (m, 4H); MS (MH+) 319.1.

Workup

  1. additionAfter addition
  2. temperaturethe reaction mixture was heated to 60° C. for 30 minutes
  3. temperatureto cool to room temperature
  4. filtrationThe reaction mixture was filtered
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with ethyl acetate (2×10 mL)
  7. dry with materialThe combined organic phases were dried (MgSO4) and volatile solvents
  8. customevaporated in vacuo
  9. customThe crude product was purified by flash chromatography
  10. washeluting with ethyl acetate/methanol/ammonia 96:3:1
  11. customThe pure product was isolated as a colourless oil
  12. customYield (0.18 g, 11%) 1H NMR (CDCl3, 500 MHz) 1.12 (d, 3H); 2.6–2.72 (br m, 2H); 3.0–3.15 (m, 5H); 6.9 (m, 2H); 7.08 (d, 1H); 7.15 (m, 1H); 7.25–7.35 (m, 4H)

Sources & evidence

ORD record
ord-34584ac20f8340d7b853f06c76aee073
Source dataset
uspto-grants-2006_12
Patent number
US07144884B2

Reaction notes

Loading…