Effect of the composition of the aqueous organic solvent on the kinetics of N-acylation of α-amino acids with 4-nitrophenyl 4-nitrobenzoate

Article abstract of DOI:10.1023/B:RUGC.0000025506.20666.d8

Equations relating the N-acylation rate constants of glycine, L-α-alanine, DL-threonine, and L-proline with 4-nitrophenyl 4-nitrobenzoate in water-acetonitrile, water-2-propanol, and water-2-methyl-2-propanol solvents to the composition of the medium were

Full text of DOI:10.1023/B:RUGC.0000025506.20666.d8

Russian Journal of General Chemistry, Vol. 74, No. 2, 2004, pp. 222 224. Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 2, 2004,
pp. 249 252.
Original Russian Text Copyright
2004 by Lebedukho, Kuritsyn, Sadovnikov.
Effect of the Composition of the Aqueous Organic Solvent
on the Kinetics of N-Acylation of -Amino Acids
with 4-Nitrophenyl 4-Nitrobenzoate
A. Yu. Lebedukho, L. V. Kuritsyn, and A. I. Sadovnikov
Ivanovo State University, Ivanovo, Russia
Received February 20, 2002
Abstract Equations relating the N-acylation rate constants of glycine, L- -alanine, DL-threonine, and
L-proline with 4-nitrophenyl 4-nitrobenzoate in water acetonitrile, water 2-propanol, and water 2-methyl-2-
propanol solvents to the composition of the medium were obtained, and reaction rate constants in water were
calculated.
It is known that the composition of the binary
solvent strongly affects both thermodynamic and ki-
netic parameters of reactions in solutions. The effect
of the composition of the aqueous organic solvent on
the reactivity [1 4] and dissociation [5 9] of -amino
acids has been studied. The use of aqueous organic
solvents allows N-acylation of -amino acids to occur
in homogeneous conditions and makes possible a
kinetic study of this reaction. Kinetics of N-acylation
of -amino acids are difficult to study in organic
solvents because of the poor solubility of these
compounds.
The error in the rate constants was no higher than
1 2% (confidence level 0.95).
As seen from Table 1, the reactivity of the -amino
acids decreases in the order Pro >> Gly > Ala >>
Ser > Thr. The N-acylation rate constant of Pro is
much higher than of the other -amino acids. The
highest reactivity of Pro owes to the fact that it is the
strongest base among the -amino acids studied [7].
The rate constants increase with increasing water
1
Table 1. Rate constants k 102 (l mol 1 s ) of N-acyla-
tion of -amino acids in systems A C at 298 K
The present work deals with the kinetics of
N-acylation of glycine (Gly), L- -alanine (Ala),
L-serine (Ser), DL-threonine (Thr), and L-proline (Pro)
with 4-nitrophenyl 4-nitrobenzoate (I) in aqueous
organic solvents, such as water acetonitrile (A),
water 2-propanol (B), and water 2-methyl-2-propanol
(C), in medium composition ranges.
Water content, wt%
Amino
acid
40
50
60
70
80
A
Gly
Ala
Ser
Pro
18.9
21.6
26.5
8.02
1.36
34.0
12.8
2.26
203
41.6
16.0
3.84
438
5.12
0.401
112
6.11
0.897
124
It is known that capable of N-acylation are the
anionic and neutral forms of -amino acids [6] (the
rate of N-acylation of the neutral form is low, and this
reaction pathway can be neglected). The N-acylation
of -amino acids occurs by scheme (1).
147
B
Gly
Ala
Ser
Thr
Pro
60.2
14.5
3.38
1.89
473
62.9
16.1
3.50
2.02
505
69.5
18.2
3.75
2.44
521
77.3
19.8
4.09
3.54
94.2
26.9
4.58
HO
NH2CHRCOO + I
ArCONHCHCOO + AtO . (1)
600
694
C
Here NH2CHRCOO is the anionic form of an
-amino acid; R, radical at the -carbon atom; and
Ar = 4-NO2C6H4.
Gly
Ala
Ser
Thr
Pro
57.5
13.2
2.47
1.55
467
61.0
13.5
2.67
1.71
494
63.3
14.2
3.05
1.79
569
67.4
18.1
3.53
2.03
608
79.5
23.5
5.12
The kinetics of a first-order reaction (1) were
followed by spectrophotometry. The rate constants (k)
calculated as described in [4] are listed in Table 1.
658
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EFFECT OF THE COMPOSITION OF THE AQUEOUS ORGANIC SOLVENT
223
Table 2. Equations of the rate constants of N-acylation of -amino acids with ester I in systems A C (r is the correlation
coefficient)
Amino acid
Equation
r
A
Gly
Ala
Ser
Pro
k = (0.763 0.032)X2 + (1.51 0.29)X1X2 + ( 4.35 0.56)X1X22
k = (0.297 0.051)X2 2+ (0.441 0.051)X1X2 + ( 1.48 0.09)X1X22
k = (6.69 0.41) 10 X2 + (0.084 0.009)X1X2 + ( 0.384 0.072)X1X22
k = (8.06 0.81)X2 + (27.7 7.5)X1X2 + ( 70.8 11.5)X1X22
B
0.985
0.998
0.989
0.989
Gly
Ala
Ser
Thr
Pro
k = (10.14 0.31)X2 + (4.75 0.63)X1X2 + ( 8.40 1.00)X1X22
k = (0.352 0.021)X2 2+ (1.39 0.42)X1X2 + ( 2.65 0.67)X1X22
0.983
0.971
0.999
0.997
0.992
k = (5.53 0.06) 10 X2 + (0.182 0.010)X1X2 + ( 0.293 0.017)X1X22
2
k = (3.57 0.08) 10 X2 + (0.21 0.08)X1X2
+
?0.42 0.11)X1X22
k = (8.75 0.28)X2 + (33.4 5.5)X1X2 + ( 56.5 7.9)X1X22
C
Gly
Ala
Ser
Thr
Pro
k = (0.991 0.09)X2 + (4.79 0.71)X1X2 + ( 7.94 0.99)X1X22
k = (0.309 0.009)X2 2+ (2.45 0.29)X1X2 + ( 3.97 0.42)X1X22
k = (6.69 0.27) 10 X2 + (0.507 0.085)X1X2 + ( 0.85 0.12)X1X22
0.988
0.994
0.992
0.981
0.999
k = (2.92 0.16) 10 X2 + (0.188 0.051)X1X2 + ( 0.289 0.071)X1X22
2
k = (7.81 0.16)X2 + (30.8 2.7)X1X2 + ( 49.1 3.9)X1X22
content of the organic solvent. At the same water
content, the rate constants in systems B and C are
higher than in system A. The same effect of the com-
position of the aqueous organic solvent has been ob-
served earlier [10] in acylation of 4-nitroaniline
with benzoyl chloride.
reagents and transitions state exerts on the reaction
rate constant. However, we failed to analyze the effect
of other solvent properties, such as polarizability and
donor and acceptor power (Koppel’ Pal’m equation
parameters), since quantitative characteristics of these
properties are known only for one-component solvents
[12].
Varied composition of the binary solvent varies the
polarity of the medium, thus affecting the rate of re-
actions in this medium.
The components of the binary solvents interact
both with each other and with both reagents, which
results in an intricate dependence of the reaction rate
constant on the mole fraction of water in the system
(Fig. 2).
Figure 1 shows the plots of N-acylation rate con-
stants vs. Kirkwood function for Gly and Ala. Similar
dependences are observed for the other -amino acids
studied. The fact that log k is nonlinear in (
(2 + 1) ( is the dielectric constant of the solvent)
points to a strong effect specific solvation of the
1)/
The effect of the composition of the aqueous or-
ganic solvent on the acylation rate constants of
-amino acids can be described by Eq. (2) [13], which
log k
0
1
1
0.9
0.2
2
0.6
0.8
0.6
0.3
2
0.480
0.483
0.486
0.489
0.7
0.8
0.9
X
(
1)/(2 + 1)
H2O
Fig. 1. Plot of logk vs. Kirkwood function for acylation
of Gly and Ala in system B at 298 K. (1) Gly and (2) Ala.
Fig. 2. Plot of k vs. mole fraction of water for acylation
of Gly and Ala in system B at 298 K. (1) Gly and (2) Ala.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 2 2004

224
LEBEDUKHO et al.
takes account of specific solvation of the reagents by
the components of the medium.
-amino acids were 0.05 0.08 M at 1:5 and 1:10
ratios of the anionic and zwitter ionic forms, depend-
ing on the composition of the binary solvent [4].
k = k1X1 + k2X2 + k12X1X2 + k12X22.
(2)
REFERENCES
Here k1 and k2 are the reaction rate constants in a pure
organic solvent and in water; k12 and k12, constants
relating to specific interaction between the components
of the solvent and the reagents [13] and accounting
for deviations from additivity; and X1 and X2, mole
fractions of the organic components and water,
respectively.
1. Kuritsyn, L.V. and Kalinina, N.V., Zh. Org. Khim.,
1988, vol. 24, no. 10, p. 2065.
2. Kuritsyn, L.V., Kalinina, N.V., and Kampal, A.K.,
Zh. Org. Khim., 1988, vol. 24, no. 12, p. 2562.
3. Kuritsyn, L.V. and Kalinina, N.V., Zh. Org. Khim.,
1994, vol. 30, no. 5, p. 723.
4. Kuritsyn, L.V., Sadovnikov, A.I., Khripkova, L.N.,
Lebedukho, A.Yu., and Shcherbakova, Yu.S., Vestn.
Ivanov. Gos. Univ., 2000, vol. 3, p. 47.
5. Kuritsyn, L.V. and Kalinina, N.V., Zh. Fiz. Khim.,
1990, vol. 64, no. 1, p. 119.
In our case, like in [14], the reaction rates in pure
solvents are very low and can be neglected. The k2,
k12, and k12 values in Eq. (2) were calculated by the
multiple regression technique [15] at a confidence
level of 0.95. Table 2 shows the rate-constant equa-
tions for the systems studied.
6. Kalinina, N.V. and Kuritsyn, L.V., Zh. Fiz. Khim.,
1996, vol. 70, no. 4, p. 760.
7. Rodante, F., Thermochim. Acta, 1989, vol. 149, no. 3,
p. 157.
8. Kuritsyn, L.V., Kalinina, N.V., and Khripkova, L.N.,
Zh. Fiz. Khim., 2000, vol. 74, no. 9, p. 1721.
9. Niasi, M.S. and Mollin, J., Bull. Chem. Soc. Jpn.,
1987, vol. 60, no. 7, p. 2605.
10. Kuritsyn, L.V., Bobko, L.A., and Besedina, L.V., Izv.
Vyssh. Uchebn. Zaved., Khim. Khim. Tekhnol., 1986,
vol. 29, no. 6, p. 39.
11. Akhadov, Ya.Yu., Dielektricheskie svoistva binarnyh
rastvoritelei (Dielectric Properties in Binary Solvents),
Moscow: Nauka, 1977, p. 399.
These equations make possible estimation of the
reaction rate constant in water k2 (coefficient of X2)
which is quite difficult to determine experimentally.
The estimates for k2 for the same -amino acids in
the three binary solvents studied are close to each
other, providing evidence for the validity of these
1
estimates. The mean k2 values (l mol 1 s ) for Gly,
Ala, Ser, Pro, and Thr are 0.97 0.14, 0.32 0.03,
2
2
(6.31 0.3) 10 , 8.2 0.4, and (3.3 0.1) 10 ,
respectively.
EXPERIMENTAL
12. Pal’m, V.A., Osnovy kolichestvennoi teorii organi
cheskikh reaktsii (Quantitative Theory of Organic
Reactions), Leningrad: Khimiya, 1977.
The rates of N-acylation of Gly, Ala, Ser, Thr, and
Pro (analytical grade all) were measured by following
the concentration of the 4-nitrophenolate ion by spec-
trophotometry ( 400 mn) using a KFK-2UKhL 4.2
photoelectrocolorimeter with a temperature-controlled
cell holder and an Shch-300 digital voltmeter. Aceto-
nitrile (analytical grade) was distilled over phosphorus
pentoxide. 2-Propanol (chemical grade) was distilled
on a column. 2-Methyl-2-propanol (chemical grade)
was purified by the procedure in [16]. Reaction mix-
tures were prepared using a concentrated solution of
NaOH (analytical grade), the concentrations of
13. Bobko, L.A., Cand. Sci. (Chem.) Dissertation, Iva-
novo, 1986.
14. Oleinik, N.M., Doctoral (Chem.) Dissertation,
Donetsk, 1984.
15. Dreiper, N. and Smit G., Prikladnoi regressionnyi
analiz (Applied Regression Analysis), Moscow:
Finansy i Statistika, 1986.
16. Maryott, A.A., J. Am. Chem. Soc., 1944, vol. 63, no. 8,
p. 3079.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 2 2004