Synthesis and crystal structure of (4S,5R)-3,4-dimethyl-5-phenyl-2- (hydroxyethylimino)-1,3-thiazolidine

Article abstract of DOI:10.1070/MC2006v016n04ABEH002211

The acid hydrolysis l-N-(N′-vinyloxyethylthiocarbamoyl)ephedrine has been investigated and the X-ray diffraction analysis of the synthesised (4S,5R)-3,4-dimethyl-5-phenyl-2-(hydroxyethylimino)-1,3-thiazolidine has been carried out.

Full text of DOI:10.1070/MC2006v016n04ABEH002211

Mendeleev Commun., 2006, 16(4), 243–244
Synthesis and crystal structure of (4S,5R)-3,4-dimethyl-5-phenyl-2-(hydroxy-
ethylimino)-1,3-thiazolidine
Arstan M. Gazaliev,a Oralgazy A. Nurkenov,a Koblandy M. Turdybekov,b Serik D. Fazylov,a Marat K. Ibraev,*a
Dastan M. Turdybekovb and Meruert B. Issabaevac
a Institute of Organic Synthesis and Coal Chemistry of the Republic of Kazakhstan, 470061 Karaganda, Kazakhstan.
Fax: +7 3212 41 3865; e-mail: mkibr@yandex.ru
b Institute of Phytochemistry, 470032 Karaganda, Kazakhstan
c Karaganda State Medical Academy, 470061 Karaganda, Kazakhstan
DOI: 10.1070/MC2006v016n04ABEH002211
The acid hydrolysis l-N-(N'-vinyloxyethylthiocarbamoyl)ephedrine has been investigated and the X-ray diffraction analysis of the
synthesised (4S,5R)-3,4-dimethyl-5-phenyl-2-(hydroxyethylimino)-1,3-thiazolidine has been carried out.
Thiourea derivatives have antimicrobial, anti-inflammatory, anti-
Ph CH(OH) CH Me
ulcerous and nematocide properties, growth regulatory activity
HCl
and high insecticidal and acaricidal activities.1,2 Interest in the
NMe
– H2O
derivatives of thioureas is caused by not only their biological
S
C
NHC2H4OCH=CH2
activity but also the fact that they are convenient synthons in
1
organic synthesis.3,4
We have synthesised l-N-(N'-vinyloxyethylthiocarbamoyl)-
ephedrine.5 Thioamide 1 was obtained through interaction between
l-ephedrine and vinyloxyethyl isothiocyanate in an alcoholic
medium.†
Ph CH CH Me
NMe
Cl
S
C
NHC2H4
O
CHMe
Ph
Ph
OH
Ph
Me
NMe · HCl
NCH2CH2OH
Me
+
S=C=N–CH2CH2OCH=CH2
OH–
S
S
NMe
Me
NH
Me
Ph
OH
NCH2CH2OH
S
2
Me
N
C–NH–CH2CH2OCH=CH2
conformation, to some extent distarted from the theoretical
(∆Cs4 = 9.57°). The C(4) atom leaves the plane of other atoms of
a cycle on 0.49 Å; the S(1), C(2), N(3) and C(5) atoms are
coplanar to within 0.05 Å. In a 4β-envelope conformation, the
methyl group at the C(4) atom and the phenyl group at the
C(5) atom of the group are oriented axially [torsion angles
S(10)S(4)N(3)S(2) –91.72° and C(11)C(5)C(2)N(3) 88.54°]. The
Me
1
There are no data on the hydrolysis of thiourea derivatives of
ephedrine alkaloids in the literature. It is known that thioamides
are susceptible to hydrolysis, especially in alkaline conditions;
the full hydrolysis resulting in carboxylic acids, hydrogen sulfide
and ammonia or amines is possible, but frequently under con-
ditions of nitrile hydrolysis, heterogeneous ring compounds or
products of oxidising splitting6 are obtained.
To study the reactivity of thioamide on the basis of l-ephedrine
containing replaced oxyethyl group, we investigated the acid
hydrolysis of l-N-(N'-vinyloxyethylthiocarbamoyl)ephedrine 1
in the presence of concentrated hydrochloric acid at ambient
temperature.‡
‡
(4S,5R)-3,4-Dimethyl-5-phenyl-2-(hydroxyethylimino)-1,3-thiazolidine
2. 10 ml of concentrated hydrochloric acid was added dropwise to 1.5 g
(0.009 mol) of l-N-(N'-2-vinyloxyethylthiocarbamoyl)ephedrine at ambient
temperature. The mixture was agitated for 3 h; then, a six-fold water
volume was added, and the solvent was distilled off in a vacuum. A 40%
aqueous solution of caustic soda was added to the residue, and the
product was extracted with benzene. The organic layer was dried over
Na2SO4, the solvent was distilled off to give 0.76 g (60%) of crystal
product, mp 108–109 °C. IR (n/cm–1): 1680–1650 (C=N), 3500–3000
(OH). 1H NMR, d: 0.92 (d, MeCH, JHH 8.6 Hz), 2.10 (s, MeN), 2.30–2.50
(m, CHMe), 4.93 (d, CHS, JHH 10.6 Hz), 7.00–7.15 (m, Ph), 3.14 (t, NCH2),
3.32 (t, CH2CH2). Found (%): C, 62.35; H, 7.12. Calc. for C13H18ON2S
(%): C, 62.40; H, 7.20.
To establish the dimensional structure of a molecule of (4S,5R)-
3,4-dimethyl-5-phenyl-2-(hydroxyethylimino)-1,3-thiazolidine 2,
X-ray diffraction analysis was performed.§ The structure of the
molecule of 2 is presented in Figure 1.
The bond lengths and valence angles are close to the routine.7
The thiazolidine ring in a molecule of 2 accepts the 4β-envelope
§
Crystal data for 2 (C13H18N2OS) at 293 K: rhombic, space group
P212121, a = 7.0181(6), b = 10.891(1), c = 17.511(2) Å, V = 1338.4(2) Å3,
dcalc = 1.242 g cm–3, Z = 4. A total of 1383 independent reflections (I > 2s)
were measured using an automatic Bruker P4 four-circle diffractometer
with a graphite monochromator using MoKα-radiation; q/2q-scanning,
2q < 50°. The structure was solved by a direct method and full-matrix
least-squares technique in an anisotropic approximation for non-hydrogen
atoms (isotropic for H atoms). Final R factor was 0.0391 (Rw = 0.1069).
Specification of the geometry was carried out by the SHELXL-97
program.
Atomic coordinates, bond lengths, bond angles and thermal param-
eters have been deposited at the Cambridge Crystallographic Data Centre
(CCDC). These data can be obtained free of charge via www.ccdc.cam.uk/
conts/retrieving.html (or from the CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44 1223 336 033; or deposit@ccdc.cam.ac.uk).
Any request to the CCDC for data should quote the full literature citation
and CCDC reference number 287033. For details, see ‘Notice to Authors’,
Mendeleev Commun., Issue 1, 2006.
†
The IR spectra were recorded on an AVATAR-320 instrument (in KBr
tablets). The 1H NMR spectra were measured on a Varian MERCURY-300
insrument at a frequency of 300 MHz in a CD3Cl solution with HMDS
as the internal standard. The melting points were measured on a Boetius
instrument.
l-N-(N'-Vinyloxyethylthiocarbamoyl)ephedrine 1. 1.5 g (0.012 mol) of
vinyloxyethyl isothiocyanate was added to 2 g (0.012 mol) of l-ephedrine
in 5 ml of ethanol. The mixture was agitated at ambient temperature for
20–30 min; then, 1/3 of solvent was distilled off and allowed to stand
overnight. The precipitate was filtered off and washed with diethyl ether
to give 2.9 g (86%) compound 1, mp 96–97 °C. IR (n/cm–1): 1530–1500
[NH–C(S)], 3400–3200 (OH). 1H NMR, d: 0.86 (d, MeCH, JHH 8.4 Hz),
2.01 (s, MeN), 2.34–2.52 (m, CHMe), 4.43 (d, CH–O, JHH 10.6 Hz),
7.10–7.24 (m, Ph), 3.06 (t, NCH2), 3.40 (t, CH2O), 6.44 (q, CH=C, JHH
cis
trans
4.6 Hz), 4.01–4.07 (dd, C=CH2, J 5.8 Hz, J
C, 61.27; H, 7.36. Calc. for C15H22O2N2S (%): C, 61.22; H, 7.48.
11.8 Hz). Found (%):
HH
HH
Mendeleev Commun. 2006 243

Mendeleev Commun., 2006, 16(4), 243–244
References
O(1)
1 H. Hirokazu, E. Isamu, K. Shingo, I. Masashi, Y. Yukari, N. Shinegori
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C(14)
C(12)
C(15)
C(13)
C(8)
2 P. S. Mital, K. Narunder and A. D. Tanega, J. Indian Chem. Soc., 1988,
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S(1)
C(7)
N(6)
C(16)
C(11)
C(2)
N(3)
C(5)
C(4)
C(9)
C(10)
Figure 1 Crystal structure of compound 2.
methyl and hydroxyethylamine groups at the atoms N(3) and
C(2) have equatorial orientations [C(5)C(4)N(3)C(9) –169.49°,
C(4)N(3)C(2)N(6) 167.0°]. The 4β-envelope conformation was
also observed in 2-p-bromophenyl-3,4-dimethyl-5-phenyl-1,3-
oxazolidine.8
Due to the presence of substituents in the oxazolidine deriva-
tives of l-ephedrine and d-pseudoephedrine at C(4), C(5), N(3),
another favourable conformation of a cycle is the 3α-envelope,
in which the methyl group at N(3) has equatorial, and the other
two substituents at the above atoms, pseudo-equatorial orienta-
tions. Exactly such a conformation is taken on by the majority
of oxazolidine derivatives of pseudoephedrine, for example,
(2S,4S,5S
)-3,4-dimethyl-5-phenyl-2-phenylethenyl-1,3-oxazolidine.9
Received: 7th July 2005; Com. 05/2542
The English language edited by Valentin V. Makhlyarchuk, Moscow
Typeset by Sergei I. Ososkov, Moscow
Printed in the UK by Cambrian Printers, Aberystwyth
244 Mendeleev Commun. 2006