Preparation of N-acyl derivatives of amino acids from acyl chlorides and amino acids in the presence of cationic surfactants. A variation of the Schotten-Baumann method of benzoylation of amino acids

Article abstract of DOI:10.1081/SCC-100000582

A very efficient method for the preparation of N-acylamino acids from the corresponding acyl chloride and amino acid is described. Amino acids, potassium carbonate, acyl chloride, and a catalytic amount of cationic surfactants were mixed in tetrahydrofuran and refluxed without ever obtaining a clear reaction mixture. After hot filtration, the product was isolated from the hot tetrahydrofuran solution in very high or almost quantitative yields.

Full text of DOI:10.1081/SCC-100000582

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PREPARATION OF N-ACYL DERIVATIVES OF AMINO
ACIDS FROM ACYL CHLORIDES AND AMINO ACIDS
IN THE PRESENCE OF CATIONIC SURFACTANTS. A
VARIATION OF THE SCHOTTEN-BAUMANN METHOD OF
BENZOYLATION OF AMINO ACIDS
Branko S. Jursic a & Donna Neumann a
a Department of Chemistry, University of New Orleans, New Orleans, Louisiana, 70148,
U.S.A.
Version of record first published: 16 Aug 2006.
To cite this article: Branko S. Jursic & Donna Neumann (2001): PREPARATION OF N-ACYL DERIVATIVES OF AMINO ACIDS
FROM ACYL CHLORIDES AND AMINO ACIDS IN THE PRESENCE OF CATIONIC SURFACTANTS. A VARIATION OF THE SCHOTTEN-
BAUMANN METHOD OF BENZOYLATION OF AMINO ACIDS, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 31:4, 555-564
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SYNTHETIC COMMUNICATIONS, 31(4), 555–564 (2001)
PREPARATION OF N-ACYL DERIVATIVES
OF AMINO ACIDS FROM ACYL
CHLORIDES AND AMINO ACIDS IN THE
PRESENCE OF CATIONIC SURFACTANTS.
A VARIATION OF THE
SCHOTTEN-BAUMANN METHOD OF
BENZOYLATION OF AMINO ACIDS
Branko S. Jursic∗ and Donna Neumann
Department of Chemistry, University of New Orleans,
New Orleans, Louisiana 70148
ABSTRACT
A very efficient method for the preparation of N-acylamino
acids from the corresponding acyl chloride and amino acid is de-
scribed. Amino acids, potassium carbonate, acyl chloride, and a
catalytic amount of cationic surfactants were mixed in tetrahydro-
furan and refluxed without ever obtaining a clear reaction mixture.
After hot filtration, the product was isolated from the hot tetrahy-
drofuran solution in very high or almost quantitative yields.
INTRODUCTION
The preparation of N-acyl derivatives of simple aliphatic amines and amides
is well established in organic synthesis (1). The treatment of acyl halides with
∗Corresponding author. E-mail: bsjcm@uno.edu
555
Copyright ꢀ 2001 by Marcel Dekker, Inc.
www.dekker.com
C

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ammonia or amines is a very general reaction for the preparation of amides (2).
The reaction is highly exothermic and must be carefully controlled, usually by
cooling the reaction mixture or performing the reaction in a very dilute solution.
In all of these reactions, a base must be present to react with the liberated hy-
drochloric acid. In not performing this step, two equivalents of the amine are
required. Because the reaction of an acyl chloride with an amine is much faster by
comparison to the hydrolysis of the acyl chloride, an aqueous alkali can be used as
a base. This modification of the reaction is called the Schotten-Baumann procedure
(3–5). In the Schotten-Baumann method of benzoylation, the amino compound, or
its salt, is dissolved or suspended in a slight excess of an 8–15% sodium hydroxide
solution. A small excess (about 10–15% more than the theoretical quantity) of
benzoyl chloride is then added and the mixture is vigorously shaken or stirred.
Benzoylation proceeds smoothly and the product (N-benzoyl derivative) usually
separates as a solid. The sodium hydroxide hydrolyzes the excess of benzoyl chlo-
ride, yielding sodium benzoate and sodium chloride, which remains in solution.
The benzoyl compounds frequently include traces of unchanged benzoyl chloride,
which thus escape hydrolysis by sodium hydroxide. It is advisable wherever pos-
sible to recrystallize, or to simply wash the crystals with alcohol (either methanol
or ethanol) because this solvent will dissolve benzoyl chloride, and the ester that
should form is soluble in alcohol.
N-acylation of amines can be accomplished with acid anhydrides (2). The
scope and mechanism of this reaction is similar to the method of preparation with
acyl chloride, except the reaction is much slower, and, in the case of aromatic
amines (anilines), the reaction requires slight heat. If the corresponding ester of an
acid and amine are used for the acylation of an amine, the reaction usually requires
an acid catalyst and extended heating of the reaction mixture. The least desirable
method of preparation of amides is directly from amines and acids (6). According
to this procedure, the mixture of an acid and an amine should be heated for a short
time (∼30 min) at elevated temperatures (if possible above 160◦C). Although
preparation of amides in this way is very simple and solvent is not required, there
are two major disadvantages: both the acid and amine, as well as the product must
be thermally stable and their boiling points should be above 200◦C. If one of
the reactant components is not thermally stable, then there are several alternative
reagents for activating the carboxylic acid, such as N,N’-dicyclohexylcarbodamine
(7–9), 1,1ꢁ-carbonyldiimidazole (1), and N-acyltetrazole (10–12).
RESULTS AND DISCUSSION
Recently, we have demonstrated that N-acyl derivatives of amino acids and
small peptides are good differentiation agents for various cancer cells (13–15).
Preparation of a wide variety of N-acyl derivatives of amino acids is desirable.

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557
First of all, the preparation of amides of amino acids is not as simple as it is for
simple aliphatic and aromatic amines. Amino acids are in Zwitterionic form and
that makes them quite insoluble in the majority of organic solvents. Certainly,
there are many methods that are currently used for the preparation of N-acyl
derivatives of amino acids and peptides (16–19). They all require several steps,
includingprotectionofthecarboxylicacidgroupoftheaminoacid, activationofthe
carboxylic amino acid group of the product acyl moiety, and finally, deprotection
of N-acylamino acid carboxylic group.
One of the methods that we initially used for the preparation of N-acyl
derivatives of amino acids is through the acylation of the amino acid ester. Amino
acid esters were prepared from amino acids and ethanol (around twenty equiva-
lents) with a 1.1 equivalent of sulfuric acid. The prepared mixture was refluxed
for several hours, ethanol was evaporated, and the oily residue was dissolved in
chloroform and carefully poured over potassium carbonate. The release of car-
bon dioxide and mixing of the chloroform mixture and solid potassium carbonate
should be gradual. After the release of carbon dioxide stopped, the chloroform
solution was separated from solid and evaporated to an oily residue. According
to the 1H-NMR, the ester is more than 97% pure and can be used without further
purification.
The esters N-acylation were performed in chloroform solution with two
equivalents of the aminoacid ester and one equivalent of acid chloride. The reaction
was instantaneously over. The chloroform solution was extracted with aqueous
hydrochloric acid and sodium hydroxide, affording a pure N-acylamino acid ester.
The N-acylamino acid ester was then hydrolyzed with an equivalent amount of
aqueous sodium hydroxide and N-acylamino acid was isolated following common
procedures for ester hydrolysis (1). This procedure gives acceptable yields (around
35–40% in regards to the amino acid or 70–85% in regards to an acyl chloride).
Furthermore, if various chloroformates are used as sources for the preparation of
N-hydroxyurea derivatives of amino acids, the yields are even lower due to their
hydrolysis in the course of the amino acid ester hydrolysis.
To avoid several steps in the N-acylamino acid, preparation we decided to
perform direct N-acylation of the amino acid with acids under the conditions of the
Schotten-Baumann method. Amino acids were dissolved in equivalent amounts
of aqueous sodium hydroxide and the corresponding acyl chloride was added.
In this method, the amino acid is fully transferred to its sodium salt and is sol-
uble in water. In the course of the reaction, water-soluble sodium chloride and
insoluble N-acylamino acid should be formed. The product should be collected
by simple filtration. In our attempts to optimize this method for the preparation
of N-benzoylmethionine and N-benzoylalanine, we always obtained a mixture
of benzoic acid, product, and the corresponding amino acid that requires sepa-
ration through crystallization or simple chromatography on silica gel with ethyl
acetate as an eluate. The yields are around 50–60%. It seems that the presence

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of amino acid actually catalyzes the hydrolysis of the acyl chloride in water
media.
Considering the fact that acyl chlorides hydrolyze very fast in moist solvents,
one can assume that, for the successful reaction between an acyl chloride and
an amino acid, water should be eliminated from the reaction media. We have
successfully used micellar media in the past to perform many organic reactions
(25,26). As a surfactant, dodecyltriammonium bromide was used. The yields for
this reaction seem to be slightly higher than direct N-acylation in water media.
We have also used reverse micelles to bring the nucleophile from solid state into
organic media through the formation of reverse micelles (20–26).
Initially, we mixed equivalent amounts of potassium carbonate and amino
acids with 1% of dodecyltriammonium bromide as a surfactant and chloroform as
a solvent. A small amount of water (5 mL) was added in chloroform (200 mL)
to form the reverse micelle. Into this suspension, an equivalent amount of ben-
zoyl chloride was added. The reaction was refluxed overnight, chloroform was
separated, evaporated, and the product crystallized. In the case of methionine and
benzoyl chloride, only 20–30% of product was isolated. The idea was to bring the
amino acid potassium salt into chloroform solution (actually in reverse micelle)
and allow it to react with acyl chloride. It seems that chloroform has too low a
polarity to accomplish this task. Chloroform was substituted with the more polar
tetrahydrofuran. All solvents and reagents were used without prior drying, so there
was a sufficient amount of water present to allow reverse micelles to form. Only
catalytic amounts of surfactant (∼1%) were used for the reaction. In this case,
almost quantitative yields of the N-acylamino acid derivatives were obtained.
We believe that the mechanism of the reaction is one that we have described
previously for some other reactions in reverse micelles (25,26). The Zwitterionic
amino acid was partially transferred in its sodium salt, releasing in this way its
amino group as a nucleophile for the reaction with the acyl chloride that is in
the tetrahydrofuran solution. Then the sodium cation in the amino acid salt was
substituted with dodecyltrimethylammonium cation, making a new amino acid
salt that is soluble in tetrahydrofuran. Now both reagents were in the same media
and formation of the amide bond was possible. The formed N-acylamino acid re-
mained in tetrahydrofuran solution, while the newly formed surfactant (now as do-
decyltrimethylammonium chloride) reacted with another molecule of amino acid
sodium salt of the amino acid that resides in solid phase, similar to the phase trans-
fer catalysis (27,28). In this way, formation of the N-acyl product after refluxing
overnight was more than 90%. Products were usually soluble in hot tetrahydro-
furan and were isolated from the reaction suspension through the separation of
the hot tetrahydrofuran solution from the solid residue and evaporation of tetrahy-
drofuran until an oily or solid residue was present. The residue was mixed with
hot petroleum ether and then refrigerated at −5◦C. The resulting crystals were

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559
separated by filtration, resulting in a pure N-acylamino acid product in more than
90% yield.
CONCLUSION
We have demonstrated that the majority of N-acylamino acid derivatives can
be prepared directly from the amino acid and acyl chlorides in one-pot syntheses.
The procedure is exceptionally simple and a large quantity of desirable product can
be obtained in this way. The procedure combines simple mixing of reactants and the
catalyst in tetrahydrofuran as a solvent, stirring which then results in a suspension
at room temperature, and finally refluxing for 5–8 h. The isolation of the product
can be obtained by filtration, evaporation of the filtrate, and crystallization of
residue after evaporation of tetrahydrofuran. This method has many advantages
over the traditional ways of preparing these derivatives, which include protection,
deprotection, and activation procedures, Due to its simplicity, it very easy to carry
out and it is also very inexpensive. Therefore, it can be applied to large-scale
industrial type N-acylamino acid preparation.
EXPERIMENTAL
All reagents are purchased from Aldrich and were used without further
purification. The melting points were determined on an Electrothermal IA 9000
Digital Melting Point Apparatus. Mass spectroscopy was performed on a Micro-
mass Quattro 2 Triple Quadrapole Mess Spectrometer. Elementary analysis was
performed by Atlantic Microlab, Inc., Norcross, GA. The 1H and 13C-NMR spec-
tra were recorded on a Varian Gemini NMR spectrophotometer (300 MHz) with
1
DMSO-d6 as a solvent. All signals H and 13C-NMR are referred to TMS as a
standard. The IR spectra were recorded as KBr pellets on Nicolet 550 Magna
Spectrophotometer. Thin layer chromatography (TLC) was performed on 0.2 mm
silica gel 60 F254 with plastic support from Aldrich.
R′
R′
O
O
Na2CO3, CH3(CH2)11N(CH3)3Br
THF
R
+
Cl
R
NH2
HOOC
HOOC
N
H
R′ = H,CH3,CH3SCH2CH2,PhCH2,CH2CH(CH3)2,CH(CH3)CH2CH3
and as amino acid H2N(CH2)5COOH and H2NCH2CONHCH2COOH
R = Ph, p-O2NPh, p-O2NPhO

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JURSIC AND NEUMANN
General Procedure for the Preparation of N-acylamino
Acid Derivatives
A tetrahydrofuran (200 mL) suspension of sodium carbonate (3.5 g,
33 mmol), dodecyltrimethylammonium bromide (0.1 g, 0.33 mmol), the corre-
sponding amino acid (33 mmol), and the corresponding acyl chloride (33 mmol)
was stirred at room temperature for approximately 4 h. Then the reaction mixture
was refluxed overnight (approximately 8–10 h) and the solid residue was sep-
arated from the tetrahydrofuran suspension and discarded. Tetrahydrofuran was
evaporated, yielding a solid residue, which was then purified by crystallization.
Preparation of N-p-nitrobenzoylglycine
The white crystals left after evaporation of tetrahydrofuran were washed
with petroleum ether and dried at 90◦C for 5 h, yielding a pure product. The
resulting yield was 89%. The melting point was determined to be 190◦–192◦C;
1
IR 3450,3150,2950,2900,1750,1550, and a broad signal 3400–2400 cm−1; H-
NMR; (DMSO-d6), δ 9.18 (1H, t, NH), 8.32 (2H, d, Ar), 8.09 (2H, d, Ar), and
3.97 (2H, d, CH2); 13C-NMR (DMSO-d6), δ 167, 161, 136, 125, 120, and 38; m/z
167(11%, O2NC6H4CONH+), 207(22%, O2NC6H4CONHCH2CO+), 225(100%,
O2NC6H4CONHCH2COOH+).
Preparation of N-p-nitrobenzoylmethionine
The crystals remaining after tetrahydrofuran evaporation were washed with
petroleum ether and dried at 90◦C for 5 h, which yielded a pure product. The re-
sulting yield was 90%. The melting point of this compound was determined to be
170◦–171◦C. IR 3300, 2900, 1730, 1650, 1600, 1530, 1350, and a broad signal at
3200–2400 cm−1; 1H-NMR (DMSO-d6), δ 8.99 (1H, d, NH), 8.32 (2H, d, Ar), 8.15
(2H, d, Ar), 4.38 (1H, m. CH), 2.52 (2H, t, CH2), 2.06 (2H, t, CH2), and 2.02 (3H,
s, CH3); 13C-NMR (DMSO-d6), δ 169, 161, 135, 125, 119, 48, 36, 26, and 10; m/z
57(43%, H2NCHCO+), 75(9%, H3CSCH2CH2+), 120(100%, C6H5CONH+),
168(12%, O2NC6H4CONH+), 251(43%, O2NC6H4CONHCH(COOH)CH2CH+2 ),
299(30%, O2NC6H4CONHCH(COOH)CH2CH2SCH3+).
Preparation of N-benzoylglycine
After evaporation of tetrahydrofuran, the solid residue was slurred in petro-
leum ether and filtered. The white crystals were washed several times with small
portions of petroleum ether (3 × 20 mL) and dried at 90◦C. The resulting yield

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561
was 90%. The melting point was determined to be 188◦–191◦C. IR 3900, 2800,
3700, 3650, 3600, 3350, 2900, 2800, 1950, 1900, 1850, 1800, 1750, 1700, 1650,
and a broad signal at 4000–2700 cm−1; 1H-NMR (DMSO-d6), δ 8.86 (1H, t, NH),
7.84 (2H, d, Ar), 7.51 (2H, t, Ar), and 3.91 (1H, d, CH2);13C-NMR (DMSO-d6),
δ167, 162, 129, 127, 124, 123, and 36.
Preparation of N-p-nitrophenyloxycarbonylglycine
An oily residue after evaporation of tetrahydrofuran crystallized by staying
1
at room temperature. H-NMR spectrum showed about 80% of the product and
about 15% p-nitrophenol. The crystals were slurred in 500 mL of benzene and
the mixture was refluxed for 10 min. The insoluble solid was separated from
the liquid and, standing at room temperature, white crystals were formed in the
benzene filtrate. They were washed with petroleum ether. The melting point was
determined to be ∼270◦C with decomposition. IR 3400, 3100, 3000, 1730, 1550,
1
1250, and a broad signal at 3400–2600 cm−1; H-NMR (DMSO-d6), δ 8.374
(1H, t, NH), 8.249 (2H, d, Ar), 7.04 (2H, d, Ar), and 3.80 (2H, d, CH2); 13C-NMR
(DMSO-d6) δ 172, 157, 154, 145, 126, 123, and 44; m/e 90 (7%, HOOCNHCH2+),
115(18%, HOOCNHCH2CO+), 140(100%, O2NC6H4O+), 169(7%, HO2NC6H4
CHO)OH+), 241(10%, O2NC6H4OCONHCH2COOH).+ Anal. calcd for C9H8N2
O6: C, 45.01; H, 3.36; N, 11.66. Found: C, 44.94; H, 3.43; N, 11.53.
Preparation of N-benzoylmethionine
After evaporation of tetrahydrofuran, white crystals were slurred in petrol-
eum ether (100 mL), separated by filtration, and washed with petroleum ether
(3 × 20 mL). The yield of N-benzoylmethionine is 92%. The melting point was
determined to be 176◦–177◦C. IR 3900, 3800, 3700, 3650, 3600, 3300, 3000, 2900,
1950, 1900, 1850, 1600, and a broad signal at 4000–2700 cm−1; 1H-NMR (DMSO-
d6) δ 8.48 (1H, d, NH), 7.80 (2H, d, Ar), 7.45 (1H, t, Ar), 7.35 (2H, t, Ar), 4.40 (1H,
m, CH), 2.50 (2H, m, CH), 2.00 (2H, t, CH2), 1.90 (1H, s, CH3); 13CNMR (DMSO-
d6), δ 169, 162, 129, 127, 124, 123, 60, 47, 26, and 10; m/e 61(20%, +H2CSCH3),
105(76%, C6H5CO+), 206(47%, C6H5CONHCH(CH2CH2+)COOH), 236(25%,
C6H5CONHCH(CH2CH2SCH3)CO+), 254(100%, C6H5CONHCH(CH2CH2
SCH3)COOH)+. Anal. calcd for C12H15NO3S: C, 56.90; H, 5.97; N, 5.53; S,
12.66. Found: C, 56.81; H, 6.02; N, 5.48; S, 12.58.
Preparation of N-benzoylalanine
Tetrahydrofuran was evaporated and the solid residue was slurred in petro-
leum ether (100 mL) and separated by filtration. White crystals were washed

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with petroleum ether (3 × 20 mL), yielding pure N-benzoylalanine. The result-
ing yield was 93%. IR 3300, 3100, 2900, 1730, and a broad signal at 3400–
2200 cm−1. 1H-NMR (DMSO-d6), δ 8.58(1H, t, NH), 7.92(2H, d, Ar), 7.56(3H,
t, Ar), 3.45(1H, dq, CH), and 2.58(3H, d, CH3). 13C-NMR (DMSO-d6), δ 173,
166, 134, 131, 128, 127, 36, and 34; m/z 176 (C6H5CONHCH(CO+)CH3), 194
(C6H5CONHCHCH(COOH)CH3+). Anal. calcd for C10H12NO3: C, 61.85; H,
6.23; N, 7.21. Found: C, 61.75; H, 6.29; N, 7.16.
Preparation of N-benzoylphenylalanine
After evaporation of tetrahydrofuran, the resulting oil was crystallized in an
ice bath. The crystals were filtered and washed with petroleum ether (3 × 20 mL),
and the filtrate was discarded. The resulting yield was 91%. The melting point
was determined to be 184◦–185◦C. IR 3500, 3100, 2950, 2750, 2650, 1750, and a
broad signal at 3400–2200 cm−1; 1H-NMR (DMSO-d6), δ 8.58, 7.90, 7.46, 7.42,
4.41, 1.71, 1.57, and 0.9; 13C-NMR (DMSO-d6), δ 170, 162, 129, 127, 124, 123,
46, 20, 18, and 17; m/z 57(100%, +H2CCH(CH3)2), 105(53%, C6H5CO+),
190(43%, C6H5CONHCH+CH2CH(CH3)2), 218(65%, C6H5CONHCH(CO+)
CH2CH (CH3)2), 236(80%, C6H5CONHCH(CH2CH(CH3)2COOH).
Preparation of N-benzoylisoleucine
After evaporation of tetrahydrofuran, the oily residue was crystallized in an
ice bath. The crystals were slurred in petroleum ether (100 mL) and washed with
petroleum ether (3 × 20 mL). The yield was 91%. The melting point was deter-
mined to be 135◦–136◦C. IR 3300, 2950, 2900, 2800, 1730, and a broad signal at
3300–2600 cm−1; 1H-NMR (DMSO-d6), δ 8.29, 7.84, 7.50, 7.43, 4.30, and 0.8;
13C-NMR (DMSO-d6), δ 169, 162, 130, 127, 123, 123, 52, 32, 21, 11, and 7; m/z
57(100%, +H2CCH(CH3)2), 105(23%, C6H5CO+), 190(27%, (C6H5CONHCH+
(CH2CH(CH3)2), 218(33%, C6H5CONHCHCO+ (CH2CH(CH3)2+), 236(25%,
C6H5CONHCHCO(CH2CH(CH3)2)COOH+). Anal. calcd for C13H17NO3: C,
66.36; H, 7.28; N, 5.95. Found: C, 66.31; H, 7.33; N, 5.88.
Preparation of N-benzoyl-6-aminohexanoic Acid
After evaporation of tetrahydrofuran, the white crystals were washed with
petroleum ether (3 × 20 mL), yielding pure N-benzoyl-6-hexanoic acid. The re-
sulting yield was 88%. IR 3900, 3800, 3700, 3650, 3600, 3300, 2900, 2800, 2700,
1950, 1900, 1850, 1800, 1700, and a broad signal at 4000–2700 cm−1; 1H- NMR

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563
(DMSO-d6), δ 8.50 (1H, t, NH), 7.83 (2H, d, Ar), 7.55 (1H, t, Ar), 7.46 (2H, t, Ar),
3.24 (2H, q, CH2), 2.20 (2H, t, CH2), 1.52 (4H, m, CH2), and 1.30 (2H, m, CH2).
13C-NMR (DMSO-d6), δ 170, 161, 130, 127, 124, 123, 35, 29, 24, 22, and 20; m/z
57(100%, +CH2CH2CH2CH3, 105(60%, C6H5CO+), 117(25%, +(CH2)5COOH),
218(27%, C6H5CONH(CH2)5CO+), 236(34%, C6H5CONH(CH2)5COOH+).
Anal. calcd for C13H17NO3: C, 66.36; H, 7.28; N, 5.95. Found: C, 66.26; H,
7.37; N, 5.90.
Preparation of N-(Nꢁ-benzoyl-2-aminoethanoyl)-2-aminoethanoic Acid
The resulting suspension was filtered while tetrahydrofuran was still hot, and
the filtrate was discarded. The remaining crystals were dissolved in 50 mL of water
at elevated temperature, and then acidified with HCl (20 mL) until the pH reached
around 2.00. The formed white crystals were separated by filtration and dried at
60◦C. The yield was 92%. IR 3350, 3100, 2970, 1730, 1250, and a broad signal
at 3400–2200 cm−1; 1H-NMR (DMSO-d6), δ 8.83(1H, d, NH), 8.45(1H, t, NH),
7.90(2H, d, Ar), 7.57(1H, t, Ar), 7.46(2H, t, Ar), 3.92(2H, d, CH2), and 3.74(2H, d,
CH2); 13C-NMR (DMSO-d6), δ 172, 169, 167, 134, 132, 128, 127, 43, and 41; m/z
105(10%, C6H5CO+), 120(15%, C6H5CONH+), 134(10%, C6H5CONHCH2+),
162 (100%, C6H5CONHCH2CO+), 219(20%, C6H5CONHCH2CONHCH2CO+),
237(45%, C6H5CONHCH2CONHCH2COOH+).
ACKNOWLEDGMENTS
This work was supported by Louisiana Educational Quality Support Fund
(LEQSF-RD-A-30).
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Received in the USA May 10, 2000

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