3-[(Benzyloxycarbonyl)amino]propionaldehyde

Chemical Properties

White to yellow crystalline powder

Uses

3-(Benzyloxycarbonylamino)propionaldehyde is used as a reagent in the synthesis of Tuberactinomycin N, a peptide antibiotic that is used as an anti-tuberculotic drug. 3-(Benzyloxycarbonylamino)propionaldehyde is also used as a reagent to prepare L-epicapreomycidine, a guanidino amino acid that is naturally found in hydrolyzates of protease inhibitors.

Synthesis

The general procedure for the synthesis of N-benzyloxycarbonyl-3-aminopropanal from 3-(benzyloxycarbonylamino)-1-propanol was as follows: PCC (8.75 g, 40.6 mmol, 1.7 eq.) and Celite (9 g) were stirred in dichloromethane (50 mL) for 5 min, followed by the addition of 3-(benzyloxycarbonylamino)-1-propanol (5.0 g, 24 mmol) dissolved in dichloromethane (30 mL). propanol (5.0 g, 24 mmol). After 4 hours of reaction, the reaction mixture was diluted with ether (100 mL) and filtered through a short pad of silica gel and Celitefilter. The residual solid was suspended in dichloromethane (25 mL) and precipitated with ether (50 mL) to pass the mixture through the same filter pad. After this process was repeated three times, the filtrate was evaporated under reduced pressure to give a yellow oil (5.0 g). Purification by column chromatography (petroleum ether solution of 40% ethyl acetate) afforded N-benzyloxycarbonyl-3-aminopropionaldehyde as a colorless viscous oil (3.0 g, 14.5 mmol) in 60% yield. rf value of 0.4 (petroleum ether solution of 50% ethyl acetate, PMA color developed); 1H NMR (CDCl3) δ: 2.75 (2H, t, J=5.7Hz. CH2), 3.49 (2H, apparent q, J=6.0 Hz, CH2), 5.09 (2H, s, CH2), 5.15 (1H, br s, NH), 7.30-7.39 (5H, m, Ar), 9.81 (1H, s, CHO); 13C NMR (CDCl3) δ: 34.6, 44.2, 66.9, 128.2 , 128.3, 128.7, 136.5, 165.4, 201.3; IR (neat) νmax: 3445, 1704, 1645 cm-1.

References

[1] Tetrahedron Letters, 2001, vol. 42, # 2, p. 183 - 185
[2] European Journal of Organic Chemistry, 2012, # 17, p. 3270 - 3277
[3] Tetrahedron, 1997, vol. 53, # 37, p. 12391 - 12404
[4] Tetrahedron Letters, 1987, vol. 28, # 33, p. 3827 - 3830
[5] Synlett, 2017, vol. 28, # 13, p. 1554 - 1557