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A Mild and Convenient

Procedure for the
Esterification of Amino Acids
a a
Ramesh C. Anand & Vimal
a
Department of Chemistry Indian Institute of
Technology, Hauz Khas, New Delhi, 110016, India
Published online: 20 Aug 2006.

To cite this article: Ramesh C. Anand & Vimal (1998): A Mild and Convenient
Procedure for the Esterification of Amino Acids, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 28:11,
1963-1965

To link to this article: http://dx.doi.org/10.1080/00397919808007170

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 SYNTHETIC COMMUNICATIONS, 28( 1l), 1963-1965 (1998)

A MILD AND CONVENIENT PROCEDURE FOR

THE ESTERIFICATION OF AMINO ACIDS
Downloaded by [California Institute of Technology] at 05:13 12 June 2013

Raniesh C. Anand' and Vimal

Department of Chemistry Indian Institute of Technology,
Hauz Khas, New Delhi-110016, India

Abstract :Chiral amino acids are esterfled in high yield and purity
at room temperature by stirring with umberlyst-15 in ulcohols

The protection of carboxylic acid group as an ester is of

considerable importance in amino acid and peptide chemistry'. In spite of
several methods for the synthesis of amino acid esters, there is still scope3
for general, mild and inexpensive procedure for the ester preparation of
amino acids. The common problem in this process is the vulnerability of
amino group to alkylation'. The basic and strong acidic conditions or
heating are likely to affect the optical purity' of chiral amino esters. Some
of the reported methods involve expensive reagents4, while others cause the
work up, isolation and purification procedures quite ci~nibersome~~~.
There
are methods which require multistep reactions to achieve this aim, i.e. N-
protection, esterification and deprotection.

* To whom correspondence should be addressed

1963

Copyright 0 1998 by Marcel Dekker, Inc.

 1964 ANAND AND VIMAL

Table
S.no. Amino Acid % yield of amino [4D27e=

ester (free base) (as hydrochlorides6)

1 L-Alanine 72' +7.3" (c 2, MeOH)

2 L-Valine 80' +22.8" (c 2, MeOH)

n
77b +7" (c 2, H20)
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3 L-Leucine 78' +20.1" (c 2 4.5, MeOH)

It
77b +17.9" (c 5, EtOH)

4 L-Serine 76' +4.8"(c 2, MeOH)

5 L-Phenylalanine 82" +38.1" (c 2, EtOH)

6 L-Methionhe 82" +26.2"(c 5, H,O)

7 L-Proline 80' -33" (C 1, H20)

8 I L-Tyrosine I 70b I -6.5" (c 2, H20)

a, methyl ester; b, ethyl ester

In the present communication we wish to report our observation that

chiral amino acids, when stirred in methanol or ethanol with
macroreticular ion exchange at room temperature, are converted into
corresponding amino esters in high yield and purity (including optical).
The amberlyst-15 in addition to acting as catalyst, give a solid support to
amino acids and make the work up and isolation procedure quite simple.
The amberlyst can be regenerated and the excess of alcohol may be
decanted from the polymer bound amino esters and reused. A typical
experimental proedure is given below and has been applied to the amino
acids given in the table.
 ESTERIFICATION OF AMINO ACIDS 1965

A solution of amino acid (8.5 m mol) in methanol (or ethanol)

containing amberlyst-15 (30 g) was stirred overnight. CH,OH was decanted
off and the amberlyst were stirred with NaHCO, solution ( l o % , 50 ml).
The aqueous layer was extracted with CH,Cl, (40 ml x 3) and the
amberlyst shaken with with CH,Cl, (40 ml x 2). The combined organic
layer was washed with brine(50 ml x 2) and dried (Na,SO,). The solvent
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was removed to leave behind TLC pure liquid or solid which was distilled
under vacuum or recrystallized for characterizations5.

REFERENCES AND NOTES

1. Barrett, G.C., ‘Amino Acids, Peptides and Proteins’ R.S.C.

Publications, London, 1996, 27, 1 and references cited therein.
2. Bodanszky, M. ‘Principles or Peptide Synthesis’, 2nd ed., Springer
- Verlag, Berlin, 1993, pp.74-88 and references cited therein
3. Kotodziejczyk, A.M. and Slebioda, M., Synthesis, 1984, 865.
4. (a) Balasubramaniyan, V., Bhatia, V.G. and Wagh, S.B.,
Tetrahedron, 1983, 39, 1475. (b) Widmer, U., Synthesis, 1983,
135. (c) Brook, M.A. and Chan, T.H., Synthesis, 1983, 201. (d)
Ameta, A., Garcia, T. and Palomo, C., Synth. Commun, 1982,12,
1139.
5. The amino esters were confirmed by comparison of their IR,NMR,
TLC and specific rotations6with the samples prepared by the known
routes’.
6. For comparison of [ayID,amino-esters were transformed into
corresponding hydrochlorides.
7. Financial support from CSIR, New Delhi through project no.
1(1343)/95-EMR-II is gratefully acknowledged.

(Received in Japan 23 October 1997)