Efficient synthesis of cis-thiazolidinethiones derived from ephedrines

Article abstract of DOI:10.1016/j.tetasy.2011.02.016

The reaction of chlorodeoxypseudoephedrine or chlorodeoxynorpseudoephedrine hydrochlorides with sodium dithiocarbonate in stirring ethanol at 0 °C to stereoselectively afford the corresponding cis-thiazolidinethiones in good yields (81% and 95%) is reported. The in situ formation of a cis-aziridine to explain the presence of trans-thiazolidinethione as a side product is proposed when the same reaction was carried out at room temperature. In addition, a 70:30 mixture of trans-isomers of a thiazolidinethione/isothiazolidinethione was formed when a cis-aziridine NH was reacted with carbon disulfide in refluxing ethanol. The analogous reaction with cis-aziridine N-Me stereoselectively affords the corresponding cis-thiazolidinethione. The ¹H and ¹³C NMR data of the thiazolidinethiones were assigned. cis-3,4-Dimethyl-5-phenylthiazolidine-2-thione was crystallized from ethanol and its X-ray diffraction structure was analyzed.

Full text of DOI:10.1016/j.tetasy.2011.02.016

Tetrahedron: Asymmetry 22 (2011) 394–398
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Efficient synthesis of cis-thiazolidinethiones derived from ephedrines
⇑
Alejandro Cruz , Itzia I. Padilla-Martínez, Efrén V. García-Báez
Departamento de Ciencias Básicas de la Unidad Profesional Interdisciplinaria de Biotecnología del IPN, Av. Acueducto s/n Barrio la Laguna Ticomán, México D.F. 07340, Mexico
a r t i c l e i n f o
a b s t r a c t
Article history:
The reaction of chlorodeoxypseudoephedrine or chlorodeoxynorpseudoephedrine hydrochlorides with
sodium dithiocarbonate in stirring ethanol at 0 °C to stereoselectively afford the corresponding cis-thiaz-
olidinethiones in good yields (81% and 95%) is reported. The in situ formation of a cis-aziridine to explain
the presence of trans-thiazolidinethione as a side product is proposed when the same reaction was car-
ried out at room temperature. In addition, a 70:30 mixture of trans-isomers of a thiazolidinethione/iso-
thiazolidinethione was formed when a cis-aziridine NH was reacted with carbon disulfide in refluxing
ethanol. The analogous reaction with cis-aziridine N–Me stereoselectively affords the corresponding
cis-thiazolidinethione. The 1H and 13C NMR data of the thiazolidinethiones were assigned. cis-3,4-
Dimethyl-5-phenylthiazolidine-2-thione was crystallized from ethanol and its X-ray diffraction structure
was analyzed.
Received 4 November 2010
Revised 4 February 2011
Accepted 17 February 2011
Available online 23 March 2011
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
asymmetric inductor. However, in recent reports, analogous chiral
4-alkylthiazolidinethiones in the form of N-acyl-thiazolidinethiones
Ephedrines 1 and 2 and their derivatives are well known to ex-
hibit biological activity and have been widely used in asymmetric
synthesis.1 There are many examples where norephedrines 1 and
ephedrines 2, as a part of a cyclic system, have been used in asym-
metric synthesis, mainly those of five-membered rings, such as
oxazolidines,2 oxazaborolidines,3 oxazolines4, and particulary oxa-
zolidinones (X = Y = O, R = H),5 oxazolidinselone (X = O, Y = Se,
R = H),6, and imidazolidinone (X = NH, Y = O, R = Me),7 Scheme 1.
have been found to be efficiently used as asymmetric inductors for
the synthesis of chiral molecules.10
Our recent research has been focused on the development of
new reactions and reagents to obtain thiazolidinethiones
(X = Y = S) from ephedrines 1,2. The synthetic methods of 1,3-
heterocycles with 2-one, 2-thione and 2-imine functional groups
derived from ephedrines have been reported in the literature,
and have recently been reviewed.8
With norephedrine 1e and ephedrine 2e, Delaunay et al.11
determined the reaction parameters for directing the formation
of the corresponding oxazolidinethiones or thiazolidinethiones
and established the mechanism and the stereochemistry of the
reactions, that is, 5 equiv of CS2 in an alkaline medium (KOH), re-
quires 24 and 16 h to obtain thiazolidinethiones in 43% (R = H)
and 60% (R = Me) yields, respectively.
X
Y
C6H5
H3C
OH
X
C6H5
H3C
O
O
O
O
S
Y
_
Se
+
N
R
NH2Cl
NH O
S
S
R
e = erythro
th = threo
1 (R = H)
On the other hand, methyldithiocarbamates 2 and 3,12 aziri-
dines 4 and 5,13 and chlorodeoxypseudoephedrines 6 and 714 have
been used as intermediates in the synthesis of thiazolidinethiones
8 and 9 (Fig. 1).
When ephedrine-N-methyldithiocarbamate 3e was refluxed in
dichloromethane in the presence of mesyl chloride and pyridine,
via an SN2 process leading to a 2-(SMe)thiazolidinium intermediate
and subsequent cleavage of the CH3–S bond, the corresponding
trans-thiazolidinethione 9t was produced in 56% yield. Kellogg
et al.13 obtained the cis-thiazolidinethione 9c in 81% yield through
a ring opening reaction of trans-aziridine 5t with CS2. However,
starting from cis-aziridine 5c or trans-aziridine 4t, the same reac-
tion was unsuccessful. Condensation of dl-chlorodeoxypseudo-
ephedrine hydrochlorides 7th14a with potassium ethyl xanthate,
2 (R = CH3)
Scheme 1. 1,3-Heterazolidines-2-heterounsaturated derived from ephedrines.
Heterocyclic sulfur analogues derived from norephedrines 1 are
scarcely used, only one example in which a oxazolidinethione
(X = O, Y = S, R = H) was used in the resolution of a racemic mixture
of chiral carboxylic acids and aminoacids has been reported.9 On
the other hand, to the best of our knowledge, there are no reports
on the use of chiral thiazolidinethione (X = Y = S, R = H) as an
⇑
Corresponding
15557296000x56325.
author.
Tel.:
+52
15557296000x56323;
fax:
+52
E-mail addresses: alecruz@ipn.mx, acruz@acei.upibi.ipn.mx, alcralmx@hotmail.
com (A. Cruz).
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.02.016

A. Cruz et al. / Tetrahedron: Asymmetry 22 (2011) 394–398
395
C6H5
H3C
C6H5
H3C
OH
S
C6H5
H3C
Cl
+
C6H5
H3C
S
S
N
_
N
R
R
N
R
SCH3
NH2Cl
R
c = cis
2 (R = H)
c = cis
4 (R = H)
e = erythro
th = threo
8 (R = H)
e = erythro
th = threo
6 (R = H)
t = trans
t = trans
3 (R = CH3)
5 (R = CH3)
9 (R = CH3)
7 (R = CH3)
Figure 1. Intermediates used in the synthesis of thiazolidinethiones 8,9.
gave low yields (26%) of the corresponding thiazolidinethione 9c.
The treatment of erythro- or threo-chlorodeoxynorephedrinesꢀHCl
6e, 6th with thiophosgene afforded the respective erythro- or
threo-1-chloro-1-phenyl-2-isothiocyanatepropanes as intermedi-
ates. Each isothiocyanate diastereoisomer was reacted with NaSH,
the reaction was stereospecific with inversion at the carbon atom
to give cis- or trans-thiazolidinethiones 8c, 8t, in high yields
(90%).14b
In 1995, we reported that chlorodeoxypseudoephedrineꢀHCl 7th
reacts with a 33% aqueous solution of sodium trithiocarbonate
(Na2CS3) in refluxing ethanol to give cis-thiazolidinethione 9c in
53% yield.14c The same reaction with chlorodeoxynorpseudoephe-
drine 6th failed to give the corresponding cis-thiazolidinethione
derivative 8c.
In spite of their high potential use in synthesis, thiazolidinethi-
ones 8 have not been exploited because there is not an efficient
synthetic method to obtain them and, the regents used are expen-
sive or dangerous. As a result, we are interested in the design of
new routes for their synthesis or to improve existing methods in
order to increase the yields. With this in mind, we decided to start
from either chlorodeoxynorpseudoephedrine 6th or chlorodeoxy-
pseudoephedrine 7th to obtain selectively cis- or trans-thiazolidin-
ethiones 8 and 9 derived from ephedrines 1 and 2.
relationships between the phenyl and the methyl groups in thiaz-
olidinethiones 8 were deduced from analysis of their 1H NMR
spectra; owing to the magnetic anisotropy of the phenyl substitu-
ent, the methyl group in the cis-compound 8c is more shielded
(1.0 ppm) than in the trans-isomer 8t (1.36). In addition, the char-
acteristic 13C NMR chemical shifts of thiocarbonyl carbon ap-
peared at 199.5 ppm for 8t and 200.3 ppm for 8c, which is in
agreement with data reported in the literature.14b On this basis,
the product represented a mixture of cis/trans-thiazolidinethiones
of 8 in a 9:1 ratio. A SN2 mechanism to explain the inversion of
configuration at C1 followed by cyclization to give the cis-isomer
is proposed in Scheme 3. On the other hand, a competitive double
SN2 mechanism on C1, followed by cyclization in which cis-
aziridine 4c as intermediate is involved to explain the presence
of the trans-isomer 8t. Analogous mechanistic observations have
been proposed to stereospecifically obtain thiazolidinethiones
from the reaction of vic-iodoalkanecarbamates with potassium
ethylxanthate then NaOH.16
To avoid the formation of the aziridine, the same reaction was
carried out at low temperature. After 6 h of stirring at 0 °C, only
cis-thiazolidinethione 8c was precipitated from ethanol as a white
powder in 95% yield.
If the 1H NMR spectra of pure cis-thiazolidinethione 8c is re-
corded in a concentrated solution, the thione tautomeric form is
observed (d NH at 8.3 ppm). However, in diluted solution, the thiol
is the observed tautomer, in this case, the SH group appeared at
1.6 ppm.
2. Results and discussion
To obtain chlorodeoxynorpseudoephedrine 6th or chlorodeoxy-
pseudoephedrine 7th as starting materials for the synthesis of
thiazolidinethiones, a stereoselective chlorination with SOCl2 was
used. It is well known that the reaction of hydrochlorides of nor-
ephedrine 1e or ephedrine 2e with thionyl chloride at room tem-
perature proceeds stereoselectively with inversion of C-1
configuration (SN2 mechanism) to give the corresponding hydro-
chlorides of chlorodeoxypseudoephedrines 6th, 7th, respectively
(Scheme 2).15
The same reactivity was observed for chlorodeoxypseudoephe-
drineꢀHCl 7th using the reaction conditions already mentioned for
6th. The reaction of 7th at 0 °C was performed and after 3 days,
white orthorhombic crystals of cis-thiazolidinethione 9c precipi-
tated from ethanol in 81% yield. The 13C NMR chemical shift at
195.0 ppm of the thiocarbonyl carbon atom, the 1H NMR chemical
shift of C–CH3 at 1.0, and the X-ray diffraction structure are indic-
ative of the formation of the cis-isomer. The NMR data of the trans-
isomer 9t is 195.0 ppm for thiocarbonyl carbon and 1.46 ppm for
the methyl hydrogens of the C–CH3 group.
Cl
+
C6H5
H3C
OH
+
C6H5
H3C
To confirm that the cis-aziridine intermediate is responsible for
trans-thiazolidinethione formation, Kelloggs method was used
with cis-aziridine 4c, 5c to obtain the corresponding trans-thiazoli-
dinethiones 8t, 9t.
SOCl2
R. T.
_
_
NH2Cl
R
NH2Cl
R
The cis-aziridines 4c, 5c were obtained when HCl salts of chlo-
rodeoxypseudoephedrines 6th, 7th were reacted with three molar
equivalents of K2CO3 in refluxing ethanol.17 The corresponding cis-
aziridine was reacted with CS2 in stirring ethanol for 48 h at 0 °C. In
the case of the reaction of cis-aziridine 4c, a 70:30 mixture of two
compounds were observed in the 1H NMR spectra. The chemical
shift of the C–CH3 of the two resulting compounds was at 1.35
and 1.44 ppm, respectively. After comparison with the reported
data, the two compounds were identified as the trans-isomers of
the thiazolidinethiones.11 The major heterocycle corresponded to
trans-thiazolidinethione 8t and the minor heterocycle was as-
signed to trans-isothiazolidinethione 10t, whose formation can
be explained by ring opening at C3 and C2 of the aziridinium by
the aziridinethiocarbamate anion of the intermediate III
1e
2e
(R = H)
6th
7th
(R = CH3)
Scheme 2. Chlorodeoxypseudoephedrine hydrochlorides from chlorination reac-
tion of ephedrines 1e and 2e.
To obtain thiazolidinethiones 8, 9, the chlorohydrates of chlo-
rodeoxypseudoephedrines 6th, 7th were reacted with one molar
equivalent of sodium dithiocarbonate ethanolic solution at room
temperature for 6 h. Next, Na2COS2 was prepared in situ from
two molar equivalents of NaOH and one molar equivalent of car-
bon disulfide in stirring ethanol at room temperature for 3 h. In
the case of chlorodeoxynorpseudoephedrineꢀHCl 6th, a white
powder solid precipitated from ethanol. The cis- and trans-

396
A. Cruz et al. / Tetrahedron: Asymmetry 22 (2011) 394–398
+
Na
S
OH
S
Cl
C6H5
H3C
Cl
+
C6H5
C6H5
H3C
S
C6H5
H3C
S
_
S
ONa
Ethanol
NaS
S
S
-H2O
OH
_
N
R
NH2Cl
H3C
NH
R
NH
R
R
I
II
8c (R = H)
6th (R = H)
7th (R = CH3)
9c (R = CH3)
Scheme 3. Mechanistic transformation to furnish cis-thiazolidinethiones from chlorodeoxypseudoephedrines.
CH3
C6H5
H3C
S
S
S
N
C6H5
H3C
S
C6H5
N
H
S
8t
NH
H
C6H5
C6H5
H3C
Cl
+
_
C6H5
H3C
H
C6H5
H3C
V
K2CO3
_
NH2Cl
CS2
N
+
N
S
N
H
H
N
H3C
H
C6H5
H3C
NH2
S
C6H5
H3C
S
H
III
4e
6th
S
CH3
S
N
10t
IV
C6H5
Scheme 4. Mechanistic transformation from cis-aziridine 4c into a mixture of trans-thiazolidinethione 8t and trans-isothiazolidinethione 10t.
S
_
S
C6H5
CH3
C6H5
+
N
N
+
CH3
S
H3C
C6H5
H3C
VI
H3C
_
S
S
S
C6H5
+
_
S
S
_
S
S
C6H5
H3C
C6H5
H3C
C6H5
H3C
CS2
CH3
S
+
N
N
N
+
N
H3C
N
CH3
CH3
S
CH3
CH3
VI
VI
5c
VII
9c
Scheme 5. Mechanistic transformation for cis-aziridine 5c into cis-thiazolidinethione 9c.
(Scheme 4). This aziridinium opening reaction has been observed
elsewere.17,18
occurred to form a five membered ring. The C12H12ꢀ ꢀ ꢀS2 distance
of 2.72(4) Å [angle of 111(3)°] is in the proper range for a strong
interaction of this kind.20
On the other hand, when cis-aziridine 5c was reacted with CS2
under the same reaction conditions, cis-thiazolidinethione 9c was
obtained stereoselectively instead of the expected trans-isomer
(Scheme 5). In this case, retention of the C1 configuration can be
explained by the self attack of the aziridinium thiocarbamate
zwitterion VI on the benzylic carbon, followed by closure of the
intermediate VII to recover the initial C1 configuration.cis-Thiazoli-
dinethione 9c was crystallized from ethanol and its molecular
structure studied by X-ray diffraction (Fig. 2). The N3–C2(S2)–S1
conjugated system is proposed since the distances are of an
intermediate value between a single (1.469 Å) and a double
(1.279 Å)19 N–C bond (N3–C2 = 1.35 Å) and a single (1.789 Å) and
3. Conclusions
The reaction of chlorodeoxypseudoepherine hydrochlorides
6th, 7th with sodium dithiocarbonate in stirring ethanol at 0 °C,
stereoselectively afforded the corresponding cis-thiazolidinethi-
ones 8c, 9c in high yield. When the same reaction was carried
out at room temperature, the formation of a cis-aziridine is pro-
posed as an intermediate to explain the presence of trans-thiazoli-
dinethiones as the secondary product.
The reaction of cis-aziridine 4c with CS2 at room temperature
affords a 70:30.mixture of the trans-isomers of thiazolidinethione
8t/isothiazolidinethione 10t, respectively. However, the reaction
with cis-aziridine 5c stereoselectively affords the corresponding
cis-thiazolidinethione 9c.
a
double (1.600 Å) C–S bond (S1–C2 = 1.741 Å and S2–
C2 = 1.659). Conjugation allows N3 to be in an sp2 hybridation, as
the angles C(4)-N(3)–C(12) = 119.9(3), C(2)–N(3)–C(4) = 116.2(3)
and C(2)–N(3)–C(12) = 121.6(3) show values close to 120°. On
the other hand, the torsion angles N(3)–C(2)–S(1)–C(5) of 5.3(3)°,
S(2)–C(2)–N(3)–C(12) of ꢁ1.8(5)° are very close to 0°, and S(2)–
C(2)–S(1)–C(5) of ꢁ177.4(2)°, S(1)–C(2)–N(3)–C(12) of 175.1(3)
are close to 180°, thus the five membered ring is almost planar.
An intramolecular contact between the hydrogen atom of the
N–CH3 group and the sulfur atom of the thiocarbonyl group
Thiazolidinethiones were assigned by 1H and 13C NMR data. The
cis- and trans-relationships between the phenyl and the methyl
groups in thiazolidinethiones were deduced from the analysis of
their 1H NMR spectra; the methyl groups in the cis-compounds
are more shielded by approximately 0.4 ppm than in the trans-iso-
mers. The thiol tautomeric form was observed in the 1H NMR

A. Cruz et al. / Tetrahedron: Asymmetry 22 (2011) 394–398
397
4.2. (1S,2S)-Chlorodeoxynorpseudoephedrine hydrochloride 6th
To the (1R,2S)-(ꢁ)-norephedrine hydrochloride 1e (1.0 g,
5.33 mmol), SOCl2 (1.43 mL, 19.8 mmol) was added slowly. After
stirring for 8 h at room temperature, the excess SOCl2 was removed
under vacuum. The resulting white solid was washed with acetone,
filtered, and recrystallized from CH3OH to give 6th as a white solid
(0.80 g, 73%), mp 205–207 °C; ½a D33
ꢂ
¼ þ10:4 (c 0.1, H2O); 1H NMR
[d, ppm, DMSO-d6]: 8.68 (br, 3H, +NH3), 7.45 (m, 5H, Ph), 5.26 (d,
1H, 3J = 9.7 Hz, C1-H), 3.83 (dq, 1H, J = 9.7, 6.7 Hz, C2-H), 1.03 (d,
3H, 3J = 6.7 Hz, C2-CH3). 13C NMR [d, ppm, DMSO-d6]: 138.08 (Ci),
129.9 (Cp), 129.65 (Co), 128.51 (Cm), 65.0 (C1), 52.92 (C2), 16.91
C2–CH3; IR (KBr, m
max/cmꢁ1): 3420 (NH3), 3058, 3014 (Ar), 2996,
2974, 2958 (CH, CH3), 716, 692 (Cl); Elemental Anal. Calcd C,
52.4461; H, 6.3570; N, 6.7956. Found: C, 53.1263; H, 6.4989; N,
7.5554.
4.3. (1S,2S)-Chlorodeoxypseudoephedrine hydrochloride 7th
The same procedure as for 6th with (1R,2S)-(ꢁ)-ephedrine
hydrochloride 2e (1.0 g, 4.96 mmol) to get 7th as a white solid
Figure 2. X-ray diffraction structure of cis-thiazolidinethione 9c. Representative
bond lengths (Å): S(1)–C(2) = 1.741(3), S(1)–C(5) = 1.828(4), S(2)–C(2) = 1.659(3),
N(3)–C(2) = 1.325(4); N(3)–C(4) = 1.471(4), C(4)–C(5) = 1.538(4). Representative
bond/valence angles (°): C(2)–S(1)–C(5) = 93.36(14), C(2)–N(3)–C(4) = 116.2(3),
C(2)–N(3)–C(12) = 121.6(3), C(4)–N(3)–C(12) = 119.9(3), S(1)–C(2)–S(2) = 119.8(2),
S(1)–C(2)–N(3) = 111.8(2), S(2)–C(2)–N(3) = 128.4(3), N(3)–C(4)–C(5) = 107.0(2),
N(3)–C(4)–C(13) = 113.0(3), S(1)–C(5)–C(4) = 103.8(2). Representative torsion/
dihedral angles (°): S(2)–C(2)–S(1)–C(5) = ꢁ177.4(2), N(3)–C(2)–S(1)–C(5) = 5.3(3),
S(1)–C(2)–N(3)–C(4) = 12.5(3), S(1)–C(2)–N(3)–C(12) = 175.1(3), S(2)–C(2)–N(3)–
C(4) = ꢁ164.5(3), S(2)–C(2)–N(3)–C(12) = ꢁ1.8(5), C(5)–C(4)–N(3)–C(2) = ꢁ27.6(4),
N(3)–C(4)–C(5)–C(6) = ꢁ97.1(3), C(13)–C(4)–N(3)–C(12) = 42.6(5), C(4)–C(5)–S(1)–
C(2) = ꢁ19.5(2). Crystal data: formula, C11H13NS2; formula weight, 223.36; crystal
system, orthorhombic; space group, P212121 (No. 19); a, b, c [Å], 19.3065(17),
(0.82 g, 75%); mp 198-200 °C; ½a D30
ꢂ
¼ þ10:5 (c 0.1, CH3OH), 1H
NMR [d, ppm, DMSO-d6]: 9.45 (br, 2H, +NH2CH3), 7.4 (m, 5H, Ph),
5.45 (d, 1H, 3J = 9.4 Hz, C1-H), 3.96 (dq, 1H, J = 9.4, 6.7 Hz, C2-H),
2.60 (s, 3H, N–CH3), 1.03 (d, 3H, 3J = 6.7 Hz, C2-CH3). 13C NMR [d,
ppm, DMSO-d6]: 137.92 (Ci), 129.98 (Cp), 129.71 (Co), 129.71
(Cm), 62.98 (C1), 58.93 (C2), 29.84 (N–CH3); 13.59 C2-CH3.
4.4. (4S,5R)-cis-4-Methyl-5-phenyl-thiazolidinethione 8c
7.0924(6), 8.2654(7); V [Ang3], 1131.78(17); Z, 4;
[1/mm], 0.431; F(0 0 0), 472; crystal size [mm], 0.26 ꢃ 0.41 ꢃ 0.50. Data collection:
temperature (K), 293; radiation [Å], MoK , 0.71073; theta min–max [°], 2.1, 25.0;
dataset, ꢁ22:22, ꢁ8:8, ꢁ9:9; Tot., uniq. data, R(int), 10,939, 1989, 0.029; observed
q l(MoKa)
(calcd) [g/cm3], 1.311;
(1S,2S)-ChlorodeoxynorpseudoephedrineꢀHCl
6th
(5.0 g,
24.27 mmol) was dissolved in 10 mL of ethanol. To this was
added a solution prepared with NaOH (2.0 g, 50 mmol) and, CS2
(2.5 g, 32.9 mmol) after stirring for 3 h in 10 mL of ethanol. The
resulting mixture was stirred for 6 h at room temperature, the
precipitate was filtered off, and washed three times with 5 mL
of water to eliminate the NaCl to get 4.75 g of 8c as a white pow-
der in 95% yield: mp = 89–90 °C; m/z: 117(55%), 123(76%),
a
data [I > 2.0r(I)], 1968. Refinement: Nref, Npar, 1989, 179; R, wR2, S, 0.0492, 0.1233,
1.27; w = 1/[/s2(Fo2) + (0.0645 P)2 + 0.2906 P], where P = (Fo2 + 2Fc2)/3; max. and av.
shift/error, 0.00, 0.00; flack x, 0.01(13); min. and max. resd. dens. [e/Å3], ꢁ0.18, 0.33.
166(27%), 209.2(100%); [
a
]
D = ꢁ33 (c 0.2, CHCl3) 1H NMR [d,
spectra, if pure cis-thiazolidinethione 8c is recorded in a dilute
solution, whereas the thione tautomer was observed in a concen-
trated solution.
The molecular structure of cis-thiazolidinethione 9c was con-
firmed by X-ray diffraction analysis. The intracyclic torsion angle
values of cis-thiazolidinetione 9c are close to 0° and 180° and are
indicative that the thiazolidine ring is near to being a planar
system.
ppm, CDCl3]: 8.28 (br, 1H, NH), 7.2–7.4 (m, 5H, Ph), 4.97 (d, 1H,
3J = 7.3 Hz, C5-H), 4.63 (dq, 1H, C4-H); 1.0 (d, 3H, 3J = 6.75 Hz,
C4-CH3). 13C NMR [d, ppm, DMSO-d6]: 201.14 (C@S), 135.6 (Ci),
129.0 (Co), 128.9 (Cp), 128.6 (Cm), 63.31 (C4), 57.85 (C5), 15.92
C4–CH3.
4.5. (4S,5R)-cis-3,4-Dimethyl-5-phenyl-thiazolidinethione 9c
The same procedure as for 8c with (1S,2S)-chlorodeoxypseudo-
ephedrineꢀHCl 7th (5.0 g, 22.72 mmol). 4.05 g of 9c crystallized
from ethanol (81% yield): mp = 61–62 °C; m/z: 117(38%),
4. Experimental
4.1. General
118(30%), 166(11%), 223 (100%); [
a]
D = ꢁ18.8 (c 3.3 ꢃ 10ꢁ3, CHCl3);
1H NMR [d, ppm, CDCl3]: 7.2–7.4 (m, 5H, Ph), 5.0 (d, 1H, 3J = 7.6 Hz,
C5-H), 4.41 (dq, 1H, C4-H); 3.27 (s, 3H, N–CH3), 1.0 (d, 3H,
3J = 6.75 Hz, C4-CH3). 13C NMR [d, ppm, DMSO-d6]: 196.31 (C@S),
135.0 (Ci), 129.1 (Co), 129.2 (Cp), 128.8 (Cm), 69.2 (C4), 52.66
(C5), 35.24 (N–CH3); 14.28 C4-CH3.
Melting points were measured on an Electrothermal IA appa-
ratus and are uncorrected. 1H and 13C NMR spectra were re-
corded on
a
Varian Mercury 300 MHz (1H, 300.08; 13C,
75.46 MHz). The spectra were measured with tetramethylsilane
as an internal reference following standard techniques. Mass
spectrometer HP 5989A, 5890 series II. Crystallographic data
(excluding structure factors) for structure of cis-thiazolidinethi-
one 9c in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication num-
ber CCDC: 798,828. X-ray diffraction cell refinement and data
collection: APEX II Area Detector;21 data reduction: SAINT;22
4.6. (4S,5S)-trans-4-Methyl-5-phenyl-thiazolidinethione 8t
(2S,3R)-cis-2-Methyl-3-phenylaziridine 4c (0.5 g, 3.76 mmol)
and 0.23 mL of CS2 (291.2 mg, 4.5 mmol) were dissolved in 3 mL
of ethanol. The resulting mixture was stirred for 48 h on an ice bath
in the refrigerator. The ethanol was evaporated to give 0.6 g of an
oily residue. The NMR spectra showed a mixture of the trans-
isomers of thiazolidinethione 8t and isothiazolidinethione 10t in
a 70:30 ratio. trans-Thiazolidinethione 8t 1H NMR [d, ppm, CDCl3]:
programs used to solve structure: SHELXS-97;23 software used to
24
prepare material for publication: WINGX
.

398
A. Cruz et al. / Tetrahedron: Asymmetry 22 (2011) 394–398
8.0 (br, 1H, NH), 7.2–7.5 (m, 5H, Ph), 4.70 (d, 1H, 3J = 8.8 Hz, C5-H),
4.33 (dq, 1H, C4-H); 1.36 (d, 3H, 3J = 6.16 Hz, C4-CH3). 13C NMR [d,
ppm, DMSO-d6]: 199.7 (C@S), 136.86 (Ci), 129.37 (Co), 129.05 (Cp),
128.26 (Cm), 67.73 (C4), 61.63 (C5), 18.72 C4-CH3.
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