TCI Practical Example: Condensation Reaction with a Capsule Reagent containing DMT-MM

We are proud to present the condensation reaction of 4-bromobenzoic acid and morpholine using the capsule reagent. This reagent can eliminate the need for weighing. Each capsule contains 0.30 mmol of DMT-MM, a condensing agent.

Used Chemicals

• 4-Bromobenzoic Acid [B0553]
• Morpholine [M0465]
• Reagents for Condensation Reactions (HPMC encapsulated) (DMT-MM) [R0294]
• Methanol

Procedure

Reagents for condensation capsule (DMT-MM) (one capsule) was added to a solution of 4-bromobenzoic acid (60 mg, 0.30 mmol, 1.0 eq.), morpholine (27.4 μL, 0.315 mmol, 1.05 eq.) in methanol (1.5 mL) at room temperature. The mixture was stirred at 30 °C for 24 hours. The reaction solution was diluted with ethyl acetate (20 mL) and filtrated through Celite pad. The filtrate was washed with sat. Na₂SO₄ aq. (30 mL), 1 mol/L HCl aq. (10 mL), sat. NaHCO₃ aq. (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 = 4:1 - 1:1) to afford (4-bromophenyl)(morpholino)methanone (70 mg, 86% yield) as a white solid.

Experimenter's Comments

• The reaction mixture was monitored by UPLC.
• The shape of the capsule is like below image and each capsule includes DMT-MM (ca. 0.30 mmol).
• The material of the capsule is water-soluble HPMC (hydroxypropyl methylcellulose).
• Saturated sodium sulfate solution used during partitioning was used to remove HPMC.

Analytical Data

(4-Bromophenyl)(morpholino)methanone

¹H NMR (400 MHz, DNSO-d₆); δ 7.65 (dt, J = 8.9 Hz, 2.1 Hz, 2H), 7.37 (dt, J = 8.5 Hz, 2.1 Hz, 2H), 3.61-3.24 (brm, 8H).

Lead Reference

• Hydrophobic Pockets of HPMC Enable Extremely Short Reaction Times in Water
  • D. Petkova, N. Borlinghaus, S. Sharma, J. Kaschel, T. Lindner, J. Klee, A. Jolit, V. Haller, S. Heitz, K. Britze, J. Dietrich, W. M. Braje, S. Handa, ACS Sustainable Chem. Eng. 2020, 8, 12612.

Other References

• 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.