Synthesis of new 3-substituted 1,3-oxazolidine-2-thiones

Article abstract of DOI:10.1134/S1070363217060299

Reaction of N-alkylsubstituted ethanolamines with carbon disulfide followed by reaction with benzoyl chloride afforded N-substituted oxazolidine-2-thiones.

Full text of DOI:10.1134/S1070363217060299

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 6, pp. 1310–1312. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © A.Т. Takibayeva, М.K. Ibraev, S.K. Kabieva, 2017, published in Zhurnal Obshchei Khimii, 2017, Vol. 87, No. 6, pp. 1038–1040.
LETTERS
TO THE EDITOR
Synthesis of New 3-Substituted 1,3-Oxazolidine-2-thiones
А. Т. Takibayeva*, М. K. Ibraev, and S. K. Kabieva
Karaganda State Technical University, bulv. Mira 56, Karaganda, 100027 Kazakhstan
*e-mail: altynarai81@mail.ru
Received February 27, 2017
Abstract—Reaction of N-alkylsubstituted ethanolamines with carbon disulfide followed by reaction with
benzoyl chloride afforded N-substituted oxazolidine-2-thiones.
Keywords: N-alkylsubstituted ethanolamines, oxazolidine-2-thione, heterocyclic compounds
DOI: 10.1134/S1070363217060299
The interest to dithiocarbamates is due both to their
biological activity and to the fact that they are
convenient synthons for preparation of heterocyclic
compounds [1–7]. In the present work, aiming at a
search for new biologically active compounds, new
derivatives of oxazolidine-2-thiones have been
synthesized. The derivatives of oxazolidine-2-thione
are known to possess valuable pharmacological pro-
perties; introduction of sulfur atom often leads to a
decrease in their toxicity [8].
presence of triethylamine leads to dithiocarbamates
2а–2e, which under the action of benzoyl chloride are
converted to N-alkyl-substituted oxazolidine-2-thiones
3а–3e. Compounds 3а–3e are white crystalline solids
readily soluble in polar solvents (Scheme 1).
The structure of the obtained compounds was
1
proved by the methods of IR and NMR Н spec-
troscopy. In the IR spectra of compounds 3а–3e in the
range 3490–3445 cm–1 a wide band of ν(О–Н)
vibration is observed. Stretching vibrations of the NO2
group appear at 1375–1330 cm–1. In the range 1365–
1325 cm–1 a weak absorption band of the С=S group is
The reaction of N-alkylsubstituted 2-vinyloxy-
ethanolamines 1а–1e with carbon disulfide in the
Scheme 1.
H+
NH
1а−1e
R
NH
R
HO
O
S
(C2H5)3N
HO
1
CS2
+
N
R
S HN(C2H5)3
2а−2e
OH
R
N
C6H5COCl
CHCl3
S
R
N
O
_C6H5COSH
S
S
O
3а−3e
O
(а),
(b),
NO2
(c),
C3H7
(d),
(e).
R = СН2CH2
C
CH2
CH2CH=CH2
СН2CH
NH2
HO
1310

1311
SYNTHESIS OF NEW 3-SUBSTITUTED 1,3-OXAZOLIDINE-2-THIONES
present as well as ν(N–Н) bands in the range 3300–
trum, ν, cm–1: 3470 br (ОН), 1355 (NO2), 1350 (С=S),
3265 (NН). H NMR spectrum, δ, ppm: 3.65 t (2Н,
1
3100 cm–1.
НОСН2СН2N, J = 5.2 Hz), 2.71 t (2Н, ОСН2СН2N,
J = 5.2 Hz), 2.67 t (2Н, NСН2СН2СН3, J = 6,4 Hz),
1.46 m (2Н, NСН2СН2СН3), 0.93 t (3Н, NСН2СН2СН3,
J = 5.9 Hz). Found, %: С 58.34; Н 12.55; N 13.68.
C5H13NO. Calculated, %: С 58.25; Н 12.62; N 13.59.
The presence of two β-hydroxy groups in com-
pound 2b points to theoretical possibility of its cycliza-
tion by either the primary or secondary ОН group. The
data of 1Н NMR spectroscopy suggest cyclization only
by the primary alcohol group, apparently, due to steric
hindrances to the secondary hydroxy group created by
the aryl substituent in the α-position.
2-Allylaminoethanol (1e) was prepared similarly
from 1.26 g (0.01 mol) of 2-vinyloxyethylallylamine.
Yield 0.71 g (56%), oily compound. IR spectrum, ν,
cm–1: 3475 ш (ОН), 1360 (NO2), 1355 (С=S), 3270
(NН). 1H NMR spectrum, δ, ppm: 3.65 t (2Н,
НОСН2СН2N, J = 5.2 Hz), 2.71 t (2Н, ОСН2СН2N,
J = 5.2 Hz), 3.46 m (2Н, NСН2СН=СН2), 5.82 m (1Н,
NСН2СН=СН2), 5.07 and 5.18 d.d (1Н, NСН2СН=СН2,
J = 10.2, 17.3 Hz). Found, %: С 59.48; Н 10.81; N 13.94.
C5H11NO. Calculated, %: С 59.41; Н 10.89; N 13.86.
N-(Ethanol-2-yl)aminopropionic acid amide (1а).
The solution of 1.58 g (0.01 mol) of β-2-vinyloxyethyl
-aminopropionic acid amide in 20 mL of 10% sulfuric
acid was stirred for 2 h at room temperature and 1 h at
40–45°C. After completionof the process, the reaction
mixture was alkalinized to рН 10 and extracted with
boiling benzene. The organic layer was separated, the
solvent was removed. Yield 1.36 g (86%), oily
compound. IR spectrum, ν, cm–1: 3490 br (ОН), 1375
3-(2-Thioxooxazolidin-3-yl)propionamide (3а).
To a solution of 1.32 g (0.01 mol) of compound 1а and
1.01 g (0.01 mol) of triethylamine in 30 mL of benzene
at 0–5°C was added dropwise a solution of 0.76 g
(0.01 mol) of carbon disulfide in 10 mL of benzene.
The reaction mixture was stirred at this temperature for
1 h, then 30 min at room temperature. The mixture was
cooled to 0°C, the solution of 0.91 g (0.01 mol) of
benzoyl chloride in 15 mL of benzene was added, and
the reaction mixture was stirred with heating (60–65°C)
for 2–3 h. After completion of the reaction the solvent
was removed at a reduced pressure. The reaction
mixture was left overnight, the precipitated crystals
were filtered off and washed with benzene. Yield 3.08 g
(77%), colorless crystals, mp 109–110°C. IR spectrum,
ν, cm–1: 3465 br (ОН), 1350 (NO2), 1345 (С=S), 3260
(NН). 1H NMR spectrum, δ, ppm: 3.62 t (2Н,
NСН2СН2О, J = 6.8 Hz), 4.12 t (2Н, NСН2СН2О, J =
6.7 Hz), 3.2 t (2Н, NСН2СН2, J = 6.7 Hz), 2.54 t (2Н,
NСН2СН2, J = 6.6 Hz). Found, %: С 41.44; Н 5.67; N
16.09. C6H10N2O2S. Calculated, %: С 41.38; Н 5.75; N
16.09.
1
(NO2), 1365 (С=S), 3300 (NН). Н NMR spectrum, δ,
ppm: 3.64 t (2Н, НОСН2СН2N, J = 5.2 Hz), 2.71 t
(2Н, НОСН2СН2N, J = 5.2 Hz), 3.19 t (2Н,
NСН2СН2, J = 6.72 Hz), 2.56 t (2Н, NСН2СН2, J =
6.59 Hz). Found, %: С 45.52; Н 9.01; N 21.29.
C5H12N2O2. Calculated, %: С 45.45; Н 9.09; N 21.21.
2-(2-Hydroxyethylamino)-1-(4-nitrophenyl)ethanol
(1b) was prepared similarly from 2.52 g (0.01 mol) of
1-(p-nitrophenyl)-2-vinyloxyethylaminoethanol. Yield
2.24 g (89%), white crystals. IR spectrum, ν, cm–1:
3485 br (ОН), 1370 (NO2), 1360 (С=S), 3280 (NН).
1Н NMR spectrum, δ, ppm: 3.65 t (2Н, НОСН2СН2N,
J = 5.2 Hz), 2.70 t (2Н, ОСН2СН2N, J = 5.2 Hz), 2.82–
2.91 m (2Н, NСН2СН), 4.83 t (1Н, NСН2СН, J =
6.8 Hz), 8.20 d (2Н, о-СН, J = 8.9 Hz), 7.61 d (2Н,
m-СН, J = 8.9 Hz). Found, %: С 53.18; Н 6.08; N
12.44. C10H14N2O4. Calculated, %: С 53.10; Н 6.19; N
12.39.
2-Benzylaminoethanol (1c) was obtained similarly
from 1.77 g (0.01 mol) of 2-vinyloxyethylbenzyl-
amine. Yield 1.06 g (60%), oily compound. IR spectrum,
ν, cm–1: 3480 br (ОН), 1365 (NO2), 1355 (С=S), 3270
(NН). 1Н NMR spectrum, δ, ppm: 3.64 t (2Н,
НОСН2СН2N, J = 5.2 Hz), 2.70 t (2Н, ОСН2СН2N,
J = 5.2 Hz), 7.25–7.30 m (5Н, С6Н5), 3.74 s (2Н,
NCH2). Found, %: С 71.60; Н 8.53; N 9.36. C9H13NO.
Calculated, %: С 71.52; Н 8.61; N 9.27.
3-[1-Hydroxy-2-(4-nitrophenyl)ethyl]oxazolidine-
2-thione (3b) was prepared similarly from 1.47 g
(0.01 mol) of compound 1b, 1.01 g (0.01 mol) of
triethylamine, 0.76 g (0.01 mol) of carbon disulfide
and 0.91 g (0.01 mol) of benzoyl chloride. Yield 2.6 g
(65%), mp 115–116°C, white crystalline compound.
IR spectrum, ν, cm–1: 3460 br (ОН), 1345 (NO2), 1340
1
2-Propylaminoethanol (1d) was prepared similarly
from 1.29 g (0.01 mol) of 2-vonyloxyethylpropyl-
amine. Yield 0.67 g (52%), oily compound. IR spec-
(С=S), 3245 (NН). H NMR spectrum, δ, ppm: 3.62 t
(2Н, NСН2СН2О, J = 6.8 Hz), 4.11 t (2Н, NСН2СН2О,
J = 6.7 Hz), 2.81–2.90 m (2Н, NСН2СН), 4.84 t (1Н,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 6 2017

1312
TAKIBAYEVA et al.
NСН2СН, J = 6.9 Hz), 8.19 d (2Н, о-СН, J = 8.8 Hz),
7.62 d (2Н, m-СН, J = 8.7 Hz). Found, %: С 49.32; Н
4.39; N 10.45. C11H12N2O4S. Calculated, %: С 49.25;
Н 4.48; N 10.45.
17.3 Hz). Found, %: С 50.43; Н 6.22; N 9.79.
C6H9NOS. Calculated, %: С 50.35; Н 6.30; N 9.79.
Melting points were measured on a Boethius
apparatus. IR spectra were taken on an AVATAR-320
NICOLET spectrophotometer in KBr. NMR spectra
were registered on a DRX-500 spectrometer with
working frequency 500 МHz in CD3OD, internal
reference TMS. The reactions were monitored and the
purity of the obtained compounds controlled by the
method of thin layer chromatography on Silufol UV-
254 plates in the system of solvents isopropyl alcohol–
ammonia–water, 7 : 2 : 1. The plates were developed
with iodine vapor.
3-Benzyl-1,3-oxazolidine-2-thione (3c) was prepared
similarly from 1.51 g (0.01 mol) of 2-benzylamino-
ethanol, 1.01 g (0.01 mol) triethylamine, 0.76 g
(0.01 mol) carbon disulfide and 0.91 g (0.01 mol) of
benzoyl chloride. Yield 3.14 g (75%), mp 183–184°C,
white crystalline compound. ИК спектр, v, см-1: 3455
1
br (ОН), 1340 (NO2), 1335 (С=S), 3225 (NН). H
NMR spectrum, δ, ppm: 3.63 t (2Н, NСН2СН2О, J =
6.8 Hz), 4.12 t (2Н, NСН2СН2О, J = 6.7 Hz), 7.23–
7.27 m (5Н, С6Н5), 3.72 s (2Н, NСН2). Found, %: С
62.25; Н 5.63; N 7.25. C10H11NOS. Calculated, %: С
62.18; Н 5.70; N 7.25.
REFERENCES
1. Melnikov, N.N. and Baskakov, Yu.А., Khimiya
gerbitsidov i regulyatorov rosta rastenii (Chemistry of
Herbicides and Plant Growth Regulators), Мoscow:
Gos. Khim. Inst, 1962.
2. Barton, S.D. and Ollis, W.D., Comprehensive Organic
Chemistry. Phosphorus and Sulfur Compounds, New
York: Pergamon Press, 1979.
3. Busev, А.I. and Byr’ko, V.М., Sovremennye problem i
metody analiza vysokochistykh veshchestv (Modern
Problems and Methods of Analysis of High-Purity
Substances), Мoscow: Mir, 1972.
3-Propyl-1,3-oxazolidine-2-thione (3d) was prepared
similarly from 1.03 g (0.01 mol) of 2-propylamino-
ethanol, 1.01 g (0.01 mol) of triethylamine, 0.76 g
(0.01 mol) of carbon disulfide and 0.91 g (0.01 mol) of
benzoyl chloride. Yield 2.9 g (79%), mp 179–180°C,
white crystalline compound. ИК спектр, ν, cm–1: 3450
1
br (ОН), 1335 (NO2), 1330 (С=S), 3215 (NН). H
NMR spectrum, δ, ppm: 3.60 t (2Н, NСН2СН2О, J =
6.8 Hz), 4.12 t (2Н, NСН2СН2О, J = 6.7 Hz), 2.71 t
(2Н, NСН2СН2СН3, J = 6.6 Hz), 1.47 m (2Н,
NСН2СН2СН3), 0.96 t (3Н, NСН2СН2СН3, J = 6.1 Hz).
Found, %: С 49.74; Н 7.52; N 9.65. C6H11NOS.
Calculated, %: С 49.65; Н 7.59; N 9.65.
4. Organicheskaya
khimiya
(Organic
Chemistry),
Tyukavkina, N.А., Ed., Мoscow: Drofa, 2002.
5. Busev, А.I., Byr’ko, V.М., and Dikusar, А.I., Zh.
Analit. Khim., 1971, vol. 26, p. 1380.
6. Korablev, М.V., Proizvodnye ditiokarbaminovykh
kislot. Khimiya, toksikologyja, farmakologiya i klini-
cheskoe primenenie (Derivatives of Dithiocarbamic
Acids. Chemistry, Toxicology, Pharmacology, and
Clinical Applications), Minsk: Belarus, 1971.
7. Gazaliev, A.M., Takibayeva, A.T., Ibraev, M.K.,
Kabieva, S.K., and Rakhimberlinova, Zh.B., Russ. J.
Gen. Chem., 2016, vol. 86, no. 6, p. 1219. doi 10.1134/
S1070363216060074
8. Kukharev, B.F., Stankevich, V.K., Lobanova, N.A.,
Klimenko, G.R., and Kukhareva, V.A., Russ. J. Org.
Chem., 2005, vol. 41, no. 1, p. 103. doi 10.1007/s11178-
005-0129-7
3-Allyl-1,3-oxazolidine-2-thione (3e) was prepared
similarly from 1.01 g (0.01 mol) of 2-allylamino-
ethanol, 1.01 g (0.01 mol) of triethylamine, 0.76 g
(0.01 mol) of carbon disulfide and 0.91 g (0.01 mol) of
benzoyl chloride. Yield 2.4 g (65%), mp 150–151°C,
white crystalline compound. IR spectrum, ν, cm–1:
3445 br (ОН), 1330 (NO2), 1325 (С=S), 3100 (NН).
1H NMR spectrum, δ, ppm: 3.64 t (2Н, NСН2СН2О,
J = 6.8 Hz), 4.13 t (2Н, NСН2СН2О, J = 6.7 Hz), 3.46
m (2Н, NСН2СН=СН2), 5.82 m (1Н, NСН2СН=СН2),
5.07 and 5.18 d.d (1Н, NСН2СН=СН2, J = 10.0,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 6 2017