Synthesis and crystal structure of (4S,5R)-2-[2-(hydroxyethyl)imino]-3,4- dimethyl-5-phenyl-1,3-thiazolidine

Article abstract of DOI:10.1134/S1070363206070231

Acid hydrolysis of l-N-[N'-(2-vinyloxy)ethylcarbamothioyl]ephedrine was studied. The synthesized (4S,5R)-2-[2-(hydroxyethyl)imino]-3,4-dimethyl-5- phenyl-1,3-thiazolidine was studied by means of X-ray diffraction. Pleiades Publishing, Inc., 2006.

Full text of DOI:10.1134/S1070363206070231

ISSN 1070-3632, Russian Journal of General Chemistry, 2006, Vol. 76, No. 7, pp. 1138 1140.
Original Russian Text O.A. Nurkenov, A.M. Gazaliev, M.K. Ibraev, D.M. Turdybekov, A.S. Sultanov, K.M. Turdybekov, S.M. Adekenov, 2006,
published in Zhurnal Obshchei Khimii, 2006, Vol. 76, No. 7, pp. 1187 1189.
Pleiades Publishing, Inc., 2006.
Synthesis and Crystal Structure
of (4S,5R)-2-[2-(Hydroxyethyl)imino]-
,4-dimethyl-5-phenyl-1,3-thiazolidine
3
a
a
a
b
O. A. Nurkenov , A. M. Gazaliev , M. K. Ibraev , D. M. Turdybekov ,
a
b
b
A. S. Sultanov , K. M. Turdybekov , and S. M. Adekenov
a
Institute of Organic Chemistry and Coal Chemistry of Kazakhstan,
ul. Alihanova 1, Karaganda, 100000 Kazakhstan
e-mail: mkibr@yandex.ru
b
Institute of Phytochemistry, Ministry of Science and Education of Kazakhstan, Karaganda, Kazakhstan
Received June 15, 2005
Abstract Acid hydrolysis of l-N-[N -(2-vinyloxy)ethylcarbamothioyl]ephedrine was studied. The syn-
thesized (4S,5R)-2-[2-(hydroxyethyl)imino]-3,4-dimethyl-5-phenyl-1,3-thiazolidine was studied by means of
X-ray diffraction.
DOI: 10.1134/S1070363206070231
Thiourea derivatives exhibit antimicrobial, anti-
inflammatory, antiulcer, and nematocide properties;
growth-regulating and high insecticide and acaricide
activity of such compounds has also been reported
[1, 2]. The interest in thiourea derivatives is explained
not only by their biological activity, but also by the
fact that they are convenient synthons in organic
synthesis, especially in heterocyclic synthesis [3, 4].
C6H5
II
I
III
The information on hydrolysis of thiourea deriva-
tives of ephedrine alkaloids is scarce. It is known that
thioamides are difficult to hydrolyze, especially in
alkaline medium; complete hydrolysis to form car-
boxylic acids, hydrogen sulfide, and ammonia or
amines is possible, but not infrequently hydrolysis
gives rise to nitroles, heterocyclic compounds, or
oxidative cleavage products [6].
Proceeding with the research toward the synthesis
and biological activity of thioamides [5], we synthe-
sized l-N-[N -(2-vinyloxy)ethylcarbamothioyl]ephed-
rine (III) by the reaction of l-ephedrine (I) with 2-vi-
nyloxyethyl isothiocyanate (II) in alcoholic medium.
+
5
C H CH
CH CH3
C6H
5
6
CH3
C6H5
CH3
H+
Cl
HO
I
NCH3
+
S
NCH HCl
S
3
NCH3
S
C NHC H O=CHCH
2 4 3
NCH CH OH
NCH CH OH
2 2
2
2
V
VI
IV
1138

SYNTHESIS AND CRYSTAL STRUCTURE
1139
O1
C14
C13
C15
C8
C16
S1
C7
C12
N6
C11
C2
C5
N3
C4
C9
C10
Structure of (4S,5R)-2-[2-(hydroxyethyl)imino]-3,4-dimethyl-5-phenyl-1,3-thiazolidine
To study the reactivity of a thioamide derived from
l-ephedrine containing a substituted 2-hydroxyethyl
group, we accomplished acid hydrolysis of compound
III in the presence of concentrated hydrochloric acid
at room temperature. It was found that the acid hyd-
rolysis provides a five-membered sulfur-containing
heterocyclic compound, viz. 2-imino-1,3-thiazolidine
IV.
88.54 , respectively). The methyl and hydroxyethyl-
3
2
5
4
3 9
amino groups on N and C are equatorial (C C N C
4
3
2
6
1
69.49 , C N C N 167.0 ). The 4 -envelope con-
formation is also characteristic of (2-p-bromophenyl)-
,4-dimethyl-5-phenyl-1,3-oxazolidine [8].
3
Because of the presence in the oxazolidine deriva-
tives of l-ephedrine and d-pseudoephedrine of sub-
4
5
3
stituents on C , C , and N , another favorable ring
conformation is 3 -envelope. In this case, the methyl
The cyclization appears to involve intramolecular
nucleophilic attack of the sulfur atom on a positively
charged carbon atom in intermediate V. Free base IV
was isolated by treatment of hydrochloride VI with
alkali.
3
group on N is equatorial, and the other two substi-
tuents on the above atoms are preudoequatorial. It is
this conformation that is characteristic of most oxazo-
lidine derivatives of pseudoephedrine, for example,
2S,4S,5S)-3,4-dimethyl-5-phenyl-2-phenylethynyl-
,3-oxazolidine [9].
(
1
Thus, the acid hydrolysis of the thiourea ephedrine
derivative at room temperature gives 2-imino-1,3-
thiazolidine IV. The steric structure of (4S,5R)-2-[2-
EXPERIMENTAL
The IR spectra were measured on a UR-20 instru-
(
hydroxyethyl)imino]-3,4-dimethyl-5-phenyl-1,3-thia-
zolidine was studied by X-ray diffraction (see figure).
1
The bond lengths and bond angles in molecule V
are close to normal values [7]. The conformation of
the thiazolidine ring in molecule IV is a slightly dis-
ent in KBr. The H NMR spectra were obtained on a
Varian Mercury-300 instrument (300 MHz) in CD Cl
3
against internal HMDS. The melting points were
measured on a Boetius hot stage.
4
4
torted 4 -envelope ( C 9.57 ). The C atom deviates
s
1
2
3
from the ring plane by 0.49 A, and the S , C , N ,
and C atoms are coplanar within 0.05 . In the
-envelope conformation, the methyl group on C
and the phenyl group on C are axial (the C C N C
X-ray diffraction analysis of (4S,5R)-2-[2-
hydroxyethyl)imino]-3,4-dimethyl-5-phenyl-1,3-
thiazolidine (4S,5R-IV). The unit cell parameters and
the intensities of 1383 unique reflections of compound
IV were measured at 20 C on a Bruker-P4 automated
5
(
4
4
5
10
4
3
2
1
1
5
2
3
and C C C N torsion angles are
91.72 and
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 7 2006

1
140
NURKENOV et al.
ganic layer was dried with Na SO , and the solvent
four-circle diffractometer (graphite monochromator,
MoK radiation, /2 scanning, 2 < 50 ). Rhombic
crystals, a 7.0181(6), b 10.891(1), c 17.511(2) ; V
2
4
was removed to obtain 0.76 g (60%) of a crystalline
1
substance, mp 108?109 C. IR spectrum, , cm :
3
3
1
1
338.4(2) , dcalc 1.242 gcm , Z 4 (C H N OS).
1680 1650 (C=N), 3500 3000 (OH). H NMR spec-
13
18
2
Space group P2 2 2 .
trum, , ppm: 0.92 d (CH CH, J 8.6 Hz), 2.10 s
1
1 1
3
HH
(
1
CH N), 2.30 2.50 m (CHCH ), 4.93 d (CHS, J
0.6 Hz), 7.00 7.15 m (C H ), 3.20 d (NCH ), 3.40 d
6 5 2
3 3 HH
Calculations involved 1341 reflections with I > 2 .
The structure was solved by the direct method and
refined by full-matrix least squares anisotropically for
non-hydrogen atoms. Hydrogen atoms were located
geometrically and fixed by the rider model. Absorp-
(
CH CH ). Found, %: C 62.35; H 7.12. C H N OS.
2 2 13 18 2
Calculated, %: C 62.40; H 7.20.
REFERENCES
tion correction by the
curves was applied. Weight
parameter 0.71073. Final divergence factors R 0.0391
1
. US Patent 5190961, Ref. Zh. Khim., 1995, 15059P.
and R 0.1069. The structure solution and refinement
W
were performed using the SHELXS-97 program.
2. Mital, P.S., Kumar, N., Tanega, A.D., J. Indian Chem.
Soc., 1988, vol. 65, no. 5, p. 382.
l-N-[N -(2-vinyloxy)ethylcarbamothioyl]ephed-
rine (III). 2-Vinyloxyethyl isothiocyanate (II), 1.5 g,
was added to a solution of 2 g of l-ephedrine (I) in
3
. Mel’nikov, N.N. and Baskakov, Yu.A., Khimiya ger-
bitsidov i regu-lyatorov rosta rastenii (Chemistry of
Herbicides and Plant Growth Regulators), Moscow:
Goskhimizdat, 1962.
5
2
ml of ethanol. The mixture was stirred at 20 C for
0 30 min, reduced by 1/3, and left to stand for 12 h
at 20 C. The precipitate that formed was filtered off
and washed with ether to obtain 2.9 g (86%) of com-
4. Barton, D.H.R. and Ollis, W.D., Comprehensive Or-
ganic Chemistry, Oxford: Pergamon, 1979, vol. 3.
1
pound III, mp 96 97 C. IR spectrum, , cm : 1530
5
6
7
8
. Gazaliev A.M., Zhurinov M.Zh., and Fazylov, S.D.,
Novye bioaktivnye proizvodnye alkaloidov (New Bio-
active Derivatives of Alkaloids), Almaty: Gylym, 1992.
1
1
500 [(NHC(S)], 3400 3200 (OH). H NMR spectrum,
,
ppm: 0.86 d (CH CH, J 8.4 Hz), 2.01 s (CH N),
3 HH 3
2
7
.34 2.52 m (CHCH ), 4.43 d (CHO, J 10.6 Hz),
.10 7.24 m (C H ), 3.06 3.40 d.d (CH ), 6.44 d
CH=C), 3.50 d (C=C ). Found, %: C 61.27; H 7.36.
3 HH
. Trofimov, B.A., Geteroatomnye proizvodnye atsetilena
(Heteroatomic Derivatives of Acetylenes), Moscow:
Nauka, 1981.
6
5
2
2
(
C H N O S. Calculated, %: C 61.22; H 7.48.
1
5
22
2
2
. Allen, F.H., Kennard, O., Watson, D.G., Brammer, L.,
Orpen, A.G., and Taylor, R., J. Chem. Soc., Perkin
Trans. 2, 1987, p. S1.
(
4S,5R)-2-[2-(Hydroxyethyl)imino]-3,4-dimethyl-
5
-phenyl-1,3-thiazolidine (4S,5R-IV). Concentrated
HCl, 10 ml, was added dropwise to 1.5 g of com-
pound III at room temperature. The mixture was
stirred for 3 h, diluted with six volumes of water, and
the water was distilled in a vacuum. The residue was
treated with 40% aqueous NaOH to ®H 10 11. The
reaction product was extracted with benzene, the or-
. Cambridge Structural Database, Version 5.23, April
2
002.
9. Nurkenov, O.A., Markova, I.V., Shalbaeva, A.B., Tur-
dybekov, K.M., and Gazaliev, A.M., Zh. Obshch. Khim.,
1999, vol. 69, no. 4, p. 679.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 7 2006