1,3-Bis(2,6-diisopropylphenyl)imidazolium Chloride (HPMC encapsulated)

• 2-Acetamido-5-bromo-4-methylpyridine [A2823]
• Phenylboronic Acid [B0857]
• Cesium Carbonate [C2160]
• Pd₂(dba)₃ (HPMC encapsulated) [R0305]
• IPr·HCl (HPMC encapsulated) [R0316]
• THF

Pd₂(dba)₃ (HPMC encapsulated) (one capsule) and IPr·HCl (HPMC encapsulated) (one capsule) were added to a solution of 2-acetamido-5-bromo-4-methylpyridine (286mg, 1.25 mmol), cesium carbonate (448 mg, 1.38 mmol, 1.1 eq.) and phenylboronic acid (229 mg, 1.88 mmol, 1.5 eq.) in THF/water (10:1, 7.1 mL) at room temperature and the reaction mixture was stirred at 100 °C for 2 hours. The solution was then diluted with ethyl acetate (3.2 mL) and sat. Na₂SO₄ aq. (3.2mL), and filtered through Celite pad. The filtrate was separated and the organic layer was washed with water (15 mL) and brine (15 mL), dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (ethyl acetate: hexane = 1:2 - 1:1) to afford 2-acetamido-4-methyl-5-phenylpyridine (294 mg, 96% yield) as a white solid.

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 Pd₂(dba)₃ (ca. 60 μmol) and IPr·HCl (ca. 125 μmol) are encapsulated in each capsule, respectively.

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

2-Acetamido-4-methyl-5-phenylpyridine

¹H NMR (400 MHz, CDCl₃); δ 9.24-9.06 (brs, 1H), 8.16 (s, 1H), 8.10 (s, 1H), 7.46-7.36 (m, 3H), 7.30-7.29 (m, 2H), 2.32 (s, 3H), 2.21 (s, 3H).

• 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.

• 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.