TCI Practical Example: Buchwald-Hartwig Amination Using Ni(tBustb)₃ Complex

We are proud to present the Buchwald-Hartwig amination of 2-chloro-p-xylene and p-anisidine using Ni(tBustb)₃ as a catalyst.

Used Chemicals

• 2-Chloro-p-xylene [C0313]
• p-Anisidine [A0487]
• Tris[trans-1,2-bis(4-tert-butylphenyl)ethene]nickel(0) (= Ni(tBustb)₃) [T4132]
• 1,1'-Bis(diphenylphosphino)ferrocene (= dppf) [B2027]
• Sodium tert-Butoxide (= NaOtBu) [S0450]

Procedure

Ni(tBustb)₃ (23 mg, 0.024 mmol, 2.5 mol%), NaOtBu (128 mg, 1.33 mmol, 1.35 eq.) and dppf (27 mg, 0.049 mmol, 5.0 mol%) were weighed and sealed in a glove box. To this, a solution of 2-chloro-p-xylene (141 mg, 0.983 mmol) and p-anisidine (145 mg, 1.18 mmol, 1.2 eq.) in dehydrated toluene (2 mL) was added and stirred for 24 hours at 100 °C. The reaction mixture was then filtered through Celite^® and the filtrate was diluted with ethyl acetate (15 mL). The organic layer was washed with water (15 mL) and brine (15 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (ethyl acetate:hexane = 1:25) to afford N-(4-methoxyphenyl)-2,5-dimethylaniline (168 mg, 75% yield) as a clear yellow liquid.
Celite is a registered trademark of IMERYS MINERALS CALIFORNIA, INC.

Experimenter’s Comments

The reaction mixture was monitored by GC.
In this experiment, commercially available dehydrated toluene was used.

Analytical Data

N-(4-Methoxyphenyl)-2,5-dimethylaniline

¹H NMR (400 MHz, CDCl₃); δ 7.05–7.01 (m, 3H), 6.89-6.84 (m, 3H), 6.45 (d, J = 7.6 Hz, 1H), 5.18 (s, 1H), 3.80 (s, 3H), 2.24 (s, 3H), 2.22 (s, 3H).

Lead Reference

• Ni(^4-tBustb)₃: A Robust 16-Electron Ni(0)-Olefin Complex for Catalysis
  • L. Nattmann, J. Cornella, Organometallics 2020, 39, 3295.