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TCI Practical Example: DMTMM-mediated Condensation

We are proud to present the amidation using DMTMM as a condensing agent applicable to the reactions in an alcohol or aqueous solvent.

Used Chemicals

• 3-Phenylpropionic Acid [H0183]
• 2-Phenylethylamine [P0085]
• DMTMM [D2919]
• Methanol

Procedure

To a solution of 3-phenylpropionic Acid (1.80 g, 12.0 mmol) and 2-phenylethylamine (1.60 g, 13.2 mmol) in MeOH (120 mL) was added DMTMM (3.65 g, 13.2 mmol) and the mixture was stirred at room temperature for 1 hour. The solvent was removed under reduced pressure. Saturated aqueous sodium bicarbonate solution (100 mL) was added to the residue. After being stirred for 10 minutes, the mixture was extracted with diethyl ether (100 mL). The separated organic layer was washed with deionized water (50 mL), 1 mol/L hydrochloric acid (50 mL), deionized water (50 mL) and brine (100 mL), dried over magnesium sulfate and filtered. The solvent was removed under reduced pressure and the residue was purified by column chromatography (ethyl acetate : hexane = 2 : 1, on silica gel), giving white solid (2.54 g, 84%).

Experimenter's Comments

The reaction mixture was monitored by TLC (hexane : ethyl acetate = 1 : 1, Rf = 0.30) and GC.

Analytical Data

N-Phenylethyl-3-phenylpropaneamide

¹H NMR (400 MHz, CDCl₃); δ 7.05–7.28 (m, 10H), 5.31 (br s, 1H), 3.46 (q, J = 6.8 Hz, 2H), 2.92 (t, J = 7.6 Hz, 2H), 2.71 (t, J = 6.8 Hz, 2H), 2.40 (t, J = 7.6 Hz, 2H).

¹³C NMR (101 MHz, CDCl₃); δ 172.0, 140.8, 138.8, 128.7 (2C), 128.6, 128.5, 128.3, 126.4, 126.2, 40.5, 38.5, 35.6, 31.6.

Lead Reference

• Formation of carboxamides by direct condensation of carboxylic acids and amines in alcohols using a new alcohol- and water-soluble condensing agent: DMT-MM
  • M. Kunishima, C. Kawachi, K. Hioki, K. Terao, S. Tani, Tetrahedron 2001, 57, 1551.

Other References

• 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium chloride: an efficient condensing agent leading to the formation of amides and esters
  • M. Kunishima, C. Kawachi, J. Monta, K. Terao, F. Iwasaki, S. Tani, Tetrahedron 1999, 55, 13159.