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279
ride than hydroxyl groups. The reaction also worked
References
equally well for other hydrophilic amines such as
ethanolamine, DL-serine methyl ester, diethanolamine,
and tris(hydroxymethyl)-aminomethane (entries 15–18).
In all of the cases investigated, as judged by HPLC, the
O-acylated products were seen in minimal amounts
(<5%), which can be readily eliminated by column
chromatography. The notable feature of the reaction is
that when the reaction temperature was elevated to
above 20°C, substantial formation of the O-acylation
side products has been observed. In addition, the
nature of the solvent system used for the reaction is of
the greatest importance. When the reaction is carried
out in either THF or H2O, only in the presence of
MgO, no appreciable amidation products were
detected. At present reaction conditions, the effective
formation of long chain amide can be attributed to the
high lipophilicity of acid chlorides which allow faster
reaction with amine other than hydroxide, a phe-
nomenon that should become more pronounced with
increasing carbon chain length of acid chlorides.
1. Bailey, P. D.; Collier, I. D.; Morgan, K. M. In Compre-
hensive Organic Functional Group Transformations;
Katritzky, A. R.; Meth-Cohn, O.; Rees, C. W., Eds.;
Pergamon: Oxford, 1995; Vol. 5, p. 264.
2. Maag, H. J. Am. Oil Chem. Soc. 1984, 61, 259.
3. Ferna´ndez-Pe´rez, M.; Otero, C. Enzym. Microb. Technol.
2001, 28, 527.
4. Maugard, T.; Remaud-Simeon, M.; Petre, D.; Monsan, P.
Tetrahedron 1997, 53, 5185.
5. Furutani, T.; Furui, M.; Ooshima, H.; Kato, J. Enzyme
Microb. Technol. 1996, 19, 578.
6. BHAP was readily prepared in 90% yield from reaction
between epichlorohydrin and an excess of ethanolamine
with reflux.
7. Typical procedure: To a solution of BHAP (1.0 g, 5.6
mmol) in H2O (2 mL) was added MgO (1.13 g, 28.0
mmol), THF (6 mL), and stirred vigorously for 30 min at
20°C. To a suspension of reaction mixture, palmitoyl
chloride (3.4 g, 12.3 mmol) in THF (2 mL) was added
dropwise for 1 h. After additional stirring for 1 h at 20°C,
the reaction mixture was filtered through a bed of Celite.
The filtrate was evaporated and extracted with ethyl ace-
tate (50 mL) and washed with water. The solvent was
dried over MgSO4 and evaporated to dryness. The residue
was purified by silica gel column chromatography
(CHCl3:MeOH=15:1) to give the desired product (3.1 g,
85%) as a white solid. Mp 71–72°C; IR wmax (KBr) 3358,
In summary, we have developed an efficient and
chemoselective amidation reaction by the reaction of
amino alcohols with acid chloride in the presence of
magnesium oxide, which will be a promising alternative
to the classical Schotten–Baumann reaction. Moreover,
this method offers wide applicability for the prepara-
tions of a range of other industrially useful alka-
nolamides. Further applications of this protocol in the
synthesis are currently in progress.
1
2910, 2860, 1609 cm−1; H NMR (CDCl3, l) 0.86 (6H, t,
J=6.6 Hz), 1.16–1.38 (48H, m), 1.52–1.65 (4H, m), 2.35
(4H, t, J=7.2), 3.21–3.42 (4H, m), 3.44–3.62 (4H, m),
3.72–3.86 (4H, m), 4.18–4.26 (1H, m); anal. calcd for
C39H78N2O5: C, 71.51; H, 12.00; N, 4.28. Found: C, 71.40;
H, 11.92; N, 4.32.
Acknowledgements
8. Guo, Z.; Dowdy, E. D.; Li, W.-S.; Polniaszek, R.;
Delaney, E. Tetrahedron Lett. 2001, 42, 1843.
The work is supported by the Korea Research Founda-
tion (2000-DP0278).