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TCI Practical Example: Ullmann-Type Coupling Reaction Using N-([Biphenyl]-2-yl)-N'-(2-phenyl-1-naphthyl)-1,2-benzenediamine

We are proud to present the Ullmann-type coupling reaction of 3-bromoquinoline and 1-(4-chlorobenzhydryl)piperazine by using N-([biphenyl]-2-yl)-N'-(2-phenyl-1-naphthyl)-1,2-benzenediamine as a catalytic ligand of copper(I) iodide. This reaction has the advantage of proceeding at room temperature.

Used Chemicals

• 3-Bromoquinoline [B1013]
• 1-(4-Chlorobenzhydryl)piperazine [C1611]
• N-([Biphenyl]-2-yl)-N'-(2-phenyl-1-naphthyl)-1,2-benzenediamine [B6606]
• Copper(I) Iodide [C2163]
• Sodium Methoxide [S0485]
• DMSO

Procedure

3-Bromoquinoline (200 mg, 961 µmol), 1-(4-chlorobenzhydryl)piperazine (331 mg, 1.15 mmol), N-([biphenyl]-2-yl)-N'-(2-phenyl-1-naphthyl)-1,2-benzenediamine (22.2 mg, 48.1 µmol), copper(I) iodide (4.6 mg, 24 µmol) and sodium methoxide (104 mg, 1.92 mmol) were dissolved in DMSO (2 mL) and stirred at room temperature for 22 hours. The reaction was quenched with water and the aqueous layer was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate:hexane = 0:100 - 30:70) to give 3-[4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl]isoquinoline as a light yellow solid (328 mg, 82% yield).

Experimenter's Comments

The reaction mixture was monitored by NMR.
The reaction was carried out under a nitrogen atmosphere.

Analytical Data

3-[4-[(4-Chlorophenyl)(phenyl)methyl]piperazin-1-yl]isoquinoline

¹H NMR (270 MHz, CDCl₃); δ 8.75 (d, J = 2.4 Hz, 1H), 7.95 (d, J = 7.3 Hz, 1H), 7.64 (dd, J = 5.9, 1.6 Hz, 1H), 7.51-7.38 (m, 6H), 7.31-7.20 (m, 6H), 4.28 (s, 1H), 3.32-3.28 (m, 4H), 2.62-2.58 (m, 4H).

Lead Reference

• Room-Temperature Cu-Catalyzed Amination of Aryl Bromides Enabled by DFT-Guided Ligand Design
  • S. T. Kim, M. J. Strauss, A.Cabré, S. L. Buchwald, J. Am. Chem. Soc. 2023, 145, 6966.