ISSN 1070-4280, Russian Journal of Organic Chemistry, 2016, Vol. 52, No. 5, pp. 753–754. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © I.B. Rozentsveig, E.V. Kondrashov, V.Yu. Serykh, O.M. Zhurba, A.N. Alekseenko, 2016, published in Zhurnal Organicheskoi
Khimii, 2016, Vol. 52, No. 5, pp. 763–764.
SHORT
COMMUNICATIONS
Synthesis of 2-(Hydroxyethyl)mercapturic Acid
from p-Acetylcysteine and 2-Bromoethanol
a
a
a
I. B. Rozentsveig , E. V. Kondrashov , V. Yu. Serykh ,
b
b
O. M. Zhurba , and A. N. Alekseenko
a
Favorskii Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: i_roz@irioch.irk.ru
b
Eastern Siberian Institute of Medical Environmental Research, Angarsk, Russia
Received January 21, 2016
DOI: 10.1134/S1070428016050237
In conditions of environmental pollution with organo-
chlorine compounds the development of efficient
methods for determining metabolites of ecotoxicants in
the human body is a topical task. One of metabolites of
electrophilic xenobiotics, in particular, of organochlo-
rine pollutants, is 2-(acetylamino)-3-[(2-hydroxy-ethyl)-
sulfanyl]propionic [2-(hydroxyethyl)mercapturic] acid 1
that as known is formed in a human body as a result of
metabolism of haloethanes or haloethylene [1, 2].
The optimization of the synthesis method showed
that in the conditions described in [3] compound 1
formed in a low yield. At varying the conditions we
found that the reaction with bromoethanol proceeded
well in the presence of excess NaOH. We failed to find
conditions for the preparation of compound 1 in a
plausible yield and of required purity when applying
chloroethanol.
The structure of synthesized compound was
reliably confirmed by spectral methods. In the IR
spectrum characteristic absorption bands are present
corresponding to groups OH, NH, C=O, C(O)OH in
In the frame of development of a HPLC-MS-MS
procedure for determining compound 1 as a metabolite
of vinyl chloride we developed a method of
preparation of compound 1 and carried out the
synthesis of a sample necessary as a chemical standard
for the performance of further studies.
1
good agreement with the expected structure. H and
1
3
C NMR spectra contain signals whose chemical
shifts and relative integral intensity and multiplicity
unambiguously prove the formation of compound 1.
The known published methods of compound 1
synthesis are based on a reaction of N-acetylcysteine 2
with iodoethanol in acetonitrile in the presence of
pyridine [3]. Compound 1 was obtained in amount of
several milligrams and with the chemical purity of
2-(Acetylamino)-3-[(2-hydroxyethyl)sulfanyl]-
propionic acid (1). In 50 mL of water was dissolved 5 g
(30.7 mmol) of N-acetylcysteine, at cooling to the
solution was added 2.48 g (62 mmol) of NaOH and
4.59 g (37 mmol) of 2-bromoethanol. The reaction
mixture was stirred for 12 h at room temperature,
evaporated in a vacuum, the residue was washed with
acetone (100 mL). The insoluble part was acidified
8
5% [3]. Taking in account the high price of
iodoethanol we found optimal conditions for the
preparation of compound 1 from bromoethanol and
chloroethanol as initial reagents.
SH
S
1
2
. NaOH
. HCl
_
O
O
OH
Br
OH
+
OH
OH
_
N
H
NaBr, NaCl
N
H
O
O
2
1
7
53