ISSN 1070-3632, Russian Journal of General Chemistry, 2010, Vol. 80, No. 5, pp. 964–967. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © N.R. Ishkulova, L.E. Oparina, L.B. Kochetova, T.P. Kustova, N.V. Kalinina, L.V. Kuritsin, 2010, published in Zhurnal Obshchei
Khimii, 2010, Vol. 80, No. 5, pp. 794–797.
Reactivity of α-Amino Acids in the N-Acylation
with Benzoic Acid Esters in Aqueous Dioxane
N. R. Ishkulova, L. E. Oparina, L. B. Kochetova,
T. P. Kustova, N. V. Kalinina, and L. V. Kuritsin
Ivanovo State University, ul. Ermaka 39, Ivanovo, 153025 Russia
fax: (4932)19326600
e-mail: kalinina_nv52@mail.ru
Received September 10, 2009
Abstract―The effect of the nitro group as a substituent in the phenoxide part of phenyl benzoate on the rate of
N-acylation of glycine, L-proline,and L-valine in the water (40 wt %)–dioxane solvent was studied. The
activation parameters of glycine reactions with the esters were measured. The existence of compensation effect
and the linear relation of the logarithms of the acylation constants to the Hammett constants were revealed. The
energy of the LUMO of esters can serve as the descriptors of the easters reactivity.
DOI: 10.1134/S1070363210050178
Study of kinetic relations in the reactions of
acylation of α-amino acids leading to the formation of
amide (peptide) bonds is important for understanding
the mechanism of peptide formation. The acyl
derivatives of amino acids having physiological and
surface activity and low toxicity are widely used in
pharmaceuticals, perfumes, cosmetics, as biodeg-
radable surfactants, corrosion inhibitors, flotation
reagents, etc.
propanol, water–2-methyl-2-propanol, and water–
acetonitrile [8–10]. A strong influence of solvent and
structure of the ester on the reaction rate was shown.
This paper presents the results of kinetic studies of
reactions of glycine (Gly), L-valine (L-Val), and L-
proline (L-Pro) with 4-nitrophenyl (I), 2,4 -, 2,5 -, and
2,6-dinitrophenyl (II–IV) and 2,4,6-trinitrophenyl (V)
benzoates in the water (40 wt %)–1,4-dioxane solvent.
It was previously found that at the acylation in
aqueous-organic medium, the main reaction form of α-
amino acids is the anion [6–10]. The reaction of the α-
amino acid anions with the acylation agents is shown
by the example of glycine.
Along with anhydrides and acid halides, as the
acylating agents in the synthesis of the amino acids
acyl derivatives activated esters of carboxylic acids are
used, and as the medium water and organic solvents
are used. Development of industrial methods for
producing acylamino acids requires development of
continuous processes, which require the data on the
reactivity of amino acids in the reactions of acyl
transfer. There is only a limited number of publications
concerning this problem [1].
NH2CH2COO− + I−V
C6H5CONHCH2COO− + RO−.
(1)
OH−
Here R are the substituents in compounds I–V.
It is known from [8–10] that when the ratio of
concentrations of anionic (Ca) and zwitter-ionic (Czw)
forms of α-amino acid is in the range from 1:4 to 1:10
the rate of hydrolysis of esters I–V can be neglected.
The necessary concentration of the amino acid anions
(~10–2 mol l–1) was created by adding a solution of a
certain amount of alkali. The reaction was performed
under first order conditions with a 100-fold excess in
concentration of amino acid compared to the ester. The
In some works the kinetics of aminolysis of esters
in nonaqueous media was studied, the influence of the
structure of acyl radical R in the acyl part of RCOX on
the reaction of the carboxylic acids phenyl esters with
various amines in dioxane [2–5]. Investigations were
carried out on the kinetics of N-acylation of α-amino
acids with benzoyl chloride in water–dioxane solvent
[6, 7]. Reactions of α-amino acids with the carboxylic
acids esters were studied in the solvents water–2-
964