Products > TCI Topics Archives > TCI Topics 2025 >

TCI Practical Example: Goldberg Amination Using the Encapsulated CuTC

We are proud to present the synthesis of 1-(2-nitrophenyl)-1H-imidazole from 1-bromo-2-nitrobenzene and imidazole via Goldberg amination with the capsule containing CuTC. This capsule reagent can omit weighing the catalyst. Each capsule includes ca. 650 μmol of CuTC.

Used Chemicals

• 1-Bromo-2-nitrobenzene [B0622]
• Imidazole [I0001]
• Potassium Carbonate [P1748]
• CuTC (HPMC encapsulated) [R0315]
• DMSO

Procedure

CuTC (HPMC encapsulated) (one capsule) was added to a solution of 1-bromo-2-nitrobenzene (131 mg, 0.65 mmol), potassium carbonate (180 mg, 1.3 mmol, 2.0 eq.) and imidazole (89 mg, 1.3 mmol, 2.0 eq.) in DMSO (3 mL) at room temperature and the reaction mixture was stirred at 140 °C for 2 hours. The solution was then diluted with ethyl acetate (15 mL) and sat. Na₂SO₄ aq. (15 mL), and filtered through Celite pad and the filtrate was extracted with ethyl acetate (15 mL × 2). The organic layer was washed with water (15 mL) and brine (10 mL), dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (ethyl acetate:hexane = 0:1 - 1:0) and to afford 1-(2-nitrophenyl)-1H-imidazole (43 mg, 36% yield) as a pale yellow solid.

Experimenter's Comments

The reaction mixture was monitored by GC.
The material of the capsule is water-soluble HPMC (hydroxypropyl methylcellulose).
The shape of the capsule is like the image below and CuTC (ca. 650 μmol) is encapsulated in each capsule.

The capsule disintegrates as shown in the image below when stirred in the solvent for about 15 minutes, releasing its content.

Analytical Data

1-(2-Nitrophenyl)-1H-imidazole

¹H NMR (400 MHz, CDCl₃); δ 8.01 (dd, J = 8.0, 1.2 Hz, 1H), 7.74 (td, J = 8.0, 1.2 Hz, 1H), 7.65 (s, 1H), 7.63 (td, J = 8.0, 1.6 Hz, 1H), 7.48 (dd, J = 8.0, 1.2 Hz, 1H), 7.23 (s, 1H), 7.08 (s, 1H).

Lead Reference

• Reagent and Catalyst Capsules: A Chemical Delivery System for Reaction Screening and Parallel Synthesis
  • N. Borlinghaus, B. Schönfeld, S. Heitz, J. Klee, S. Vukelić, W. M. Braje, A. Jolit, J. Org. Chem. 2021, 86, 1357.

Other Reference

• HPMC: A Biomass-Based Semisynthetic Sustainable Additive Enabling Clean and Fast Chemistry in Water
  • S. Sharma, T. N. Ansari, S. Handa, ACS Sustainable Chem. Eng. 2021, 9, 12719.