A facile method for the synthesis of hydrazine-4-oxothiazolidine and imino-5-oxothiadiazine derivatives from 1,4-disubstituted thiosemicarbazides

Article abstract of DOI:10.1002/jhet.1655

1,4-Disubstituted thiosemicarbazides reacted with dimethyl acetylenedicarboxylate with formation of (2-hydrazono-4-oxothiazolidin-5- ylidene)acetates and, in one case, a (2-imino-1,3,4-thiadiazin-5-on-6-ylidene) acetate. Several mechanistic options involving nucleophilic interaction are presented. The structures of all newly synthesized compounds were identified by ¹H NMR, ¹³C NMR, COSY, HMQC and HMBC spectral data.

Full text of DOI:10.1002/jhet.1655

44
A Facile Method for the Synthesis of Hydrazine-4-oxothiazolidine and
Imino-5-oxothiadiazine Derivatives from 1,4-Disubstituted
Thiosemicarbazides
Vol 51
a
a
a
b
c
*
Alaa A. Hassan, Ashraf A. Aly, Tarek I. M. Bedair, Alan B. Brown and Talaat I. El-Emary
aChemistry Department, Faculty of Science, Minia University, El-Minia 61519, Egypt
bChemistry Department, Florida Institute of Technology, 150 W University BlvdMelbourne, Florida 32901
cChemistry Department, Faculty of Science, Assiut University, Assiut, Egypt
*
E-mail: alaahassan2001@yahoo.com
Received December 8, 2011
DOI 10.1002/jhet.1655
Published online 7 October 2013 in Wiley Online Library (wileyonlinelibrary.com).
S
R
O
R
H
R
N
N
O
N
S
H
N
N
R'
NH
N
H
H
EtOH
R'
+
+
N
S
R'
MeO2C
CO2Me
N
O
OMe
O
OMe
1,4-Disubstituted thiosemicarbazides reacted with dimethyl acetylenedicarboxylate with formation of
(2-hydrazono-4-oxothiazolidin-5-ylidene)acetates and, in one case, a (2-imino-1,3,4-thiadiazin-5-on-6-
ylidene)acetate. Several mechanistic options involving nucleophilic interaction are presented. The structures
1
of all newly synthesized compounds were identified by H NMR, 13C NMR, COSY, HMQC and HMBC
spectral data.
J. Heterocyclic Chem., 51, 44 (2014).
INTRODUCTION
In the present work, we have explored the effect of acyl
group in acylthiosemicarbazides on the nucleophilicity of the
nitrogen atoms by examining the reactions of selected acylthio-
semicarbazides 1a–h with dimethyl acetylenedicarboxylate
and, in addition, by intramolecular cyclo-condensation under
refluxing in ethanol. To elucidate the tautomeric states and
structure of the products as well as to characterize the products
and confirm the identities of the new compounds, we used IR,
1H NMR and 13C NMR, COSY, HMQC and HMBC as well
as mass spectrometry.
Acylthiosemicarbazides represent versatile synthons for
various syntheses of nitrogen–sulfur heterocycles. The
acylthiosemicarbazide moiety provides an opportunity to
perform cyclocondensations as well as addition-cyclization
reactions. The products of these reactions are thiazin-2-yli-
dene [1], thiazoline [2], triazole [3], and imidazolidine [4,5]
derivatives. It has been reported that the reaction of dimethyl
acetylenedicarboxylate with thiocarbamides led to 4-oxathia-
zolidine derivatives [6–9]. Thiazolidine-4-one ring systems
are known to posses anti-bacterial [10], antituberculosis
[11–13], antiviral [14–16], anticancer [17–20], and antioxi-
dant [21] activities.
RESULTS AND DISCUSSION
Treatment of 1a–h with one molar equivalent of dimethyl
acetylenedicarboxylate (DMAD, 8) in ethanol at reflux
resulted in the formation of thiazolidinones 9a–h as major
products; the yields are 66–79% in all cases but 9a. Adduct
9a was isolated in 59% yield, along with thiadiazinone 10
(28%) as minor product (Scheme 2).
On the other hand, thiourea has been a subject of intensive
investigations for its performance in the construction of
anion receptors via double hydrogen-bonding interaction
by thioureido-NH donors [22–25]. This interest has recently
been enhanced because of the promising progress in
thiourea-based organocatalysts, again via hydrogen bonding
[26–29]. Obviously, the bonding ability of the thiourea
moiety is an important parameter, which in principle
depends on the acidity of thioureido-NH protons and the
number of binding sites [30–32].
Recently, it has been reported that the acylthiosemicarba-
zides 1 reacted with tetracyanoethylene (TCNE, 2), in
dimethylformamide to form thiadiazoles 3 and oxadiazoles 4
[33]. Upon addition of TCNE to 1 (R = benzyl and allyl) in
chlorobenzene, the thiadiazole, pyrazole, and oxadiazine
derivatives 5–7, respectively, were isolated (Scheme 1) [33].
Compound 9a. To illustrate the structure elucidation of
compounds 9a–h, we choose 9a, the major reaction product
from equimolar quantities of 1a and DMAD (8). IR spectra
showed three carbonyl absorption bands at 1750, 1700 and
1660 cmꢀ1, and a band at 1615 cmꢀ1 that was assigned to
C═N vibration.
The 1H NMR spectrum of 9a showed one methoxyl group at
dH = 3.82, two phenyl groups in the range of dH =6.97–7.79,
one vinylic proton at dH = 7.02, and NH at dH = 9.42.
In principle, the reaction could form any of compounds
© 2013 HeteroCorporation

January 2014
A Facile Method for the Synthesis of Hydrazine-4-oxothiazolidine and
45
Imino-5-oxothiadiazine Derivatives from 1,4-Disubstituted Thiosemicarbazides
Scheme 1
O
NC
NC
CN
CN
N
N
H
N
H
N
DMF
R
+
Ph
N
H
R
Ph
N
H
X
S
3, X = S
4, X = O
1
2
C6H5Cl
O
O
Ph
O
Ph
Ph
N
N
N
N
N
NC
NC
R
+
NH
CN
+
H2N
CN
N
H
S
NC
CN
5
7
6
1,3 and 4: R= PhCO, Ph, PhCH2, CH2=CH-CH2, EtOOC
5: R = PhCH2, CH2=CH-CH2
9a–13 (Figure 1), depending on the sites of nucleophilic
attack. In each DMAD-derived substructure C-100 is the
lactam carbonyl, C-200 is the proton-bearing carbon, and
C-300 is the (quaternary) carbon. Thus, in 11 and 12, C-100,
200, 300 are attached in that order; in 9a, 10, and 13, C-300 is
between C-100 and C-200.
at dC = 161.90, giving HMBC correlation with H-200 at
dH = 7.02, must be the lactam carbonyl C-100.
The aromatic carbon multiplicities show unambiguous
positional assignments. The para-carbons C-4,40 give double
triplets, the meta-carbons C-3,30 give double doublets, and
the ortho-carbons H-2,20 give double-double doublets, one
doublet coupling constant being large in each case, The ipso
carbons C-1,10 appear as triplets with small coupling
constants; the benzamide carbonyl does not show resolvable
coupling, but gives HMBC correlation with H-3 and N-H.
The coupling networks corresponding to each ring can be
deduced from the correlation patterns.
From the 13C NMR data, structures with C═S double
bonds, such as 11, can be immediately ruled out: the
C = X signals are not far enough downfield (dC ≤ 166.03).
The methoxy protons (dH = 3.82) give HMQC correlation
with the attached carbon at dC = 52.71 and HMBC correla-
tion with the ester carbonyl at dC = 166.03. The signal
Compound 10. The minor product of the same reaction is
assigned as (Z)-methyl 2-((Z)-4-benzoyl-5-oxo-2-(phenylimino)-
1,3,4-thiadiazinan-6-ylidene)acetate 10, as one of the
products from the reaction between 1a and 8. (It has been
reported that compounds having thiadiazinan moiety
showed potent antibacterial activity [36,37]).
Scheme 2
S
H
R
N
+
+
MeO2C
CO2Me
N
H
N
H
R'
1a-h
8
Structures with C═S double bonds, such as 11, can again
be ruled out from the 13C C = X chemical shifts (dC ≤ 165.94).
The methoxyl protons are distinctive at dH = 3.81; this signal
gives HSQC correlation with the attached carbon at
dC = 52.66 and HMBC correlation with the ester carbonyl at
dC = 165.94. The signals at dC = 163.61 and 163.52, giving
HMBC correlation with H-200 at dH =6.87 and H-2 at
dH = 7.84, must be lactam carbonyl C-100 and benzamide
carbonyl in some order. They almost overlap, in both the
decoupled and 1H-coupled spectra. In the coupled spectrum,
the upfield of the two is a doublet or triplet with J= 5.7 Hz;
the downfield signal is broadened by a coupling whose J is
small. For structural assignment, the critical coupling is
between C-I0 and H-200, which would be a doublet coupling
if observed; the coupling of the benzamide carbonyl to the
EtOH
COPh
N
O
R
O
N
NH
H
N
R'
Ph
N
N
S
S
O
OMe
O
OMe
9a-h
1,9: a, R = Ph; R' = PhCO; b, R = Ph; R' = OC
10
N
c, R = Ph; R' = O2S
CH3
O S
CH3
d, R = CH2=CH-CH2, R' =
2
; f, R = CH2=CH-CH2; R' = PhCO
CH3
e, R = PhCO, R' =
O2S
g, R = CH2=CH-CH2; R' = OC
; h, R = R' = PhCO
N
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

46
A. A. Hassan, A. A. Aly, Tarek I. M. Bedair, A. B. Brown, and T. I. El-Emary
Vol 51
4`
3.6
9.3
5.7
5.7
Triplet:
3`
O
O
1`
2`
1``
N
O
N
S
1``
NH
3``
2``
No coupling:
N
3``
O
9.3
S
2``
N
HN
C
1
O
OMe
Observed:
O
OMe
2
6.5
5.7
5.7
5.7
10
9a
3
Doublet:
O
O
N
12.2
11.4
COPh
COPh
N
N
Figure 2. Coupling trees for amide carbons under various coupling scenarios.
O
S
Ph
O
S
N
and further argues that C-100 and H-200 are mutually cis, as
depicted in structures 9 and 10. Compound 9a was assigned
as (Z)-9a; the (E) isomer of 9a is not expected to give a
coupling this large, but (Z)-10 is. Therefore, the structure is
assigned as (Z)-10.
OMe
OMe
Ph
12
11
O
The aromatic signals are so close together that only partial
assignment is possible. The signal at dC = 127.47, which gives
HSQC correlation with H-2, is assigned as C-2. The broad-
ened double triplet at dC = 131.73, which gives HMBC
correlation with C-2, must be one of the other carbons in
the benzamide ring, and its multiplicity requires it be the
para-carbon C-4. The double-double doublet at dC = 128.20,
with three different coupling constants, is assigned as the
remaining ortho-carbon C-20 because of its multiplicity: the
ortho-carbons of 9a show similar coupling. The three signals
between dC = 129.14–128.48 must represent C-3,30,40; the
smallest of the three (dC = 129.06) is assigned as para-carbon
C-40, because the meta-carbon signals represent two carbons
each. Para-carbons normally appear as double triplets, and
this signal is therefore so assigned, although the downfield line
is not resolved from the next signal downfield; it should
be emphasized that the observed signals are consistent with
this assignment. The two remaining signals must be the
meta-carbons C-3,30.
Most of the aromatic carbons are in an envelope that gives
HSQC correlation with the signals at dH =7.58–7.51; the
correlations are not resolved. C-4, which is downfield of
the other protonated aromatic carbons, correlates only with
the signal at dH = 7.58, which therefore must include H-4.
The signals at dH =7.58 and dH = 7.51 have equal integrals;
this requires that H-40 also appear at dH = 7.58, because all
the other signals represent two protons. Because H-2 gives
COSY correlation with dH = 7.51 but not dH = 7.58, H-3 must
have dH = 7.51. The proton integrals then require that one pair
of the remaining protons H-20,30 has dH = 7.58 and the other
has dH =7.51 in some order.
O
NH
1``
N
3``
2``
N
S
O
OMe
13
Figure 1. Possible products from the reaction between 1a–h and
dimethyl acetylenedicarboxylate (8).
ortho-protons would be a triplet coupling. We assign the
coupling as a doublet and the upfield carbon as C-100, based
on the following reasoning (Figure 2).
In the decoupled 13C spectrum, the signals are 9.3 Hz apart.
In the coupled spectrum, if the upfield signal was a triplet, its
center line should still be 9.3 Hz from the downfield signal,
with smaller lines on either side. (The downfield line of the
triplet might or might not be resolved from the other signal:
the key observation is the line spacing.) On the other hand,
if the upfield signal was a doublet, its downfield line should
be 2.8 Hz from the original positions and 6.5 Hz from the
downfield signal; there should be no line 9.3 Hz from the
downfield signal, but the upfield line of the doublet should
be 12.1–12.2 Hz from the downfield signal. The middle
of the three observed lines is found to be 5.7 Hz from the
downfield signal, and indeed there is no line 9 Hz from the
downfield signal.
As in other compounds of the series, the magnitude of the
coupling between C-100 and H-200 (J = 5.6) requires a three-
bond not two-bond coupling [34,35], excluding structures 12,
The downfield of the two ipso-carbons, at dC = 134.08,
gives HMBC correlation with both dH = 7.58 and dH = 7.51;
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2014
A Facile Method for the Synthesis of Hydrazine-4-oxothiazolidine and
47
Imino-5-oxothiadiazine Derivatives from 1,4-Disubstituted Thiosemicarbazides
Scheme 3
the upfield ipso-carbon at dC = 132.89 correlates with dH =7.51
only. Because the envelope at dH = 7.51 contains meta-protons
(and perhaps ortho) from both rings, whereas that at dH =7.58
contains neither H-2 nor H-3, the signal at dC = 134.08 is
assigned as C-10 and that at dC = 132.89 as C-1.
S
SH
H
N
H
N
R
R
N
H
N
H
R'
N
H
N
R'
1a-h
+
Although the starting materials 1a–h possess four possible
nucleophilic sites, namely the three nitrogens and the sulfur,
both observed cyclization pathways appear to involve
intermediate 14, which would form by conjugate addition of
the thiocarbonyl group to the C–C triple bond of 8 (Scheme 3).
Attack on the proximal ester group by either N-1 or N-4 would
then lead to 9a–h or 10, respectively. It is not obvious why 9a
alone furnishes a minor adduct of type 10.
MeO2C
CO2Me
8
O
R
H
N
N
R'
N
R
N
- MeOH
H
N
H
R`
CO2Me
S
N
S
MeO
O
9a-h
H
MeO2C
CONCLUSION
14
R'
N
Reactions of 1,4-disubstituted thiosemicarbazides 1a–h with
dimethyl acetylenedicarboxylate (8) lead to intermolecular
nucleophilic attack on the C ꢁ C triple bond of (8), followed
by heterocyclization to give either oxothiazolidines (9a–h)
or an oxothiadiazine (10), with elimination of a molecule of
MeOH.
O
NH
H
N
- MeOH
N
R'
R
N
R
H
S
N
S
MeO2C
O
OMe
10
R = Ph, R' = PhCO
CO2Me
EXPERIMENTAL
Melting points were determined with a Gallenkamp melting
point apparatus (Loughborough, UK) and were uncorrected. IR
spectra were obtained in KBr disks on a Shimadzu 408 instrument
1
1750, 1700, 1660 (CO), 1615 (C═N), 1595 (Ar-C═C). H NMR
(CDCl3) 9.42 (s, 1H; NH), 7.79 (d, J= 7.6, 2H; H-2), 7.47
(t, J= 7.4, 1H; H-4), 7.35 (t, J= 8.0, 2H; H-30), 7.32 (t, J=7.9, 2H;
H-3), 7.19 (t, J=7.4, 1H, H-40), 7.02 (s, 1H; H-200), 6.97 (d, J=7.6,
2H; H-20), 3.82 (s, 3H; OCH3). 13C NMR (CDCl3) 166.03
(q, J=3.9; CO2CH3), 165.13 (broad quin; PhCON), 161.90
(d, J=5.6; C-100), 149.60 (s; C═N), 146.08 (t, J= 9.7; C-1), 138.53
(s; C-300), 132.82 (dt, Jd = 162.1, Jt = 7.5; C-4), 130.34 (t, J = 8.1;
C-10), 129.56 (dd, J = 161.1, 8.3; C-30), 128.65 (dd, J = 162.6, 7.7;
C-3), 127.79 (ddd, J = 161.0, 7.3, 6.4; C-2), 125.80 (dt, Jd = 162.7,
Jt = 7.6; C-40), 121.05 (ddd, J = 160.3, 7.5, 5.6; C-20), 118.08
(d, J = 173.6; C-200), 52.71 (q, J = 148.0; OCH3). MS (EI): m/z
(%) = 381 (21), 237 (17), 135 (24), 119 (41), 105 (100), 77 (67),
59 (56). Anal. C19H15N3O4S (381.41): Calcd C, 59.83; H, 3.96;
N, 11.02; S, 8.41. Found: C, 60.02; H, 4.09; N, 10.89; S, 8.29.
(Kyoto, Japan); absorption frequencies (n) are reported in cmꢀ1
.
NMR spectra (1H, 400 MHz; 13C, 100 MHz) were recorded at
room temperature in CDCl3 or DMSO-d6 using a Bruker AV
400 spectrometer (Karlsruhe, Germany). Chemical shifts are
expressed in
d (ppm) versus tetramethylsilane (TMS) = 0.
Coupling constants are stated in Hz; 1H-coupled 13C NMR
spectra were measured using gated decoupling. Correlations were
established using 1H-1H COSY, HMBC, and HSQC experiments.
Mass spectra were recorded with a Varian MAT CH-5 spectrom-
eter (70 eV) (Germany). Elemental analyses were carried out at
Microanalytical Center, Cairo University, Egypt. Preparative layer
chromatography (plc) used air dried 1.0 mm thick layers of slurry
applied silica gel (Merck Pf 254) on 48ꢂ 20-cm glass plates using
the solvents listed. Zones were detected by indicator fluorescence
quenching upon 254 nm light and eluted with acetone.
(Z)-Methyl
thiadiazin-6-ylidene)acetate (10).
2-((Z)-4-benzoyl-5-oxo-2-(phenylimino)-1,3,4-
Pale yellow crystals
(0.106 g, 28%); mp 274–276ꢃC (acetonitrile). IR (KBr): 3230
Starting materials. Thiosemicarbazides 1a–h were prepared
according to the literature: 1a [32,38], 1b [31,39], 1c [40], 1d [41],
1e–g [42], and 1h [30]. DMAD (8) was bought from Fluka (Germany).
1
(NH), 1730, 1695, 1660 (CO), 1610 (C═N), 1590 (Ar-C═C). H
NMR (DMSO-d6) 11.30 (s, 1H; N-H), 7.84 (d, J=7.1, 2H; H-2),
7.58 (bt, J= 6.9, 4H; H-20/30,4,40), 7.51 (m, 4H; H-30/20), 6.87
(s, 1H; H-200), 3.81 (s, 3H; OCH3). 13C NMR (DMSO-d6) 165.94
(q, J=3.4; CO2CH3), 163.61 (b; PhCON), 163.52 (d, J=5.7; C-100),
157.56 (b; C═N), 140.91 (s; C-300), 134.08 (bt, J=8.8; C-10),
132.89 (bt, J= 8.8; C-1), 131.73 (bdt, Jd = 162.6, Jt =8.7; C-4),
129.14 (dd, J= 163.2, 7.8; C-3/30), 129.06 (dt, J= 159.5, 7.1; C-40),
128.48 (dd, J=162.0, 6.7; C-30/3), 128.20 (ddd, J= 164.7, 7.4, 5.1;
C-20), 127.47 (bd, J= 161.7; C-2), 115.12 (d, J= 172.3; C = 200),
52.66 (q, J=148.1; OCH3). MS (EI): m/z (%) = 381 (22), 353 (36),
276 (19), 105 (82), 59 (100). Anal. C19H15N3O4S (381.41): Calcd C,
59.83; H, 3.96; N, 11.02; S, 8.41. Found: C, 60.02; H, 4.09; N
10.87; S, 8.58.
Reactions of 1,4-disubstituted thiosemicarbazides 1a–h with
DMAD (8).
A mixture of 1,4-disubstituted thiosemicarbazide
(1a–h, 1 mmol) and DMAD (8, 1 mmol) in absolute ethanol was
refluxed for 3 h. The solvent was evaporated and the residue was
subjected to plc using toluene/ethyl acetate (10:3) as eluent to give
two zones (in case of the reaction between 1a and 8), whereas only
one zone was observed in the reactions between 1b–h and 8. The
zones were removed and extracted to give the thiazolone and
thiazinone derivatives 9 and 10, respectively.
(Z)-Methyl 2-((E)-2-(2-benzoylhydrazono)-4-oxo-3-phenyl-
thiazolidin-5-ylidene)acetate (9a).
Pale yellow crystals
(0.225 g, 59%), mp 192–194ꢃC (ethanol). IR (KBr): 3245 (NH),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

48
A. A. Hassan, A. A. Aly, Tarek I. M. Bedair, A. B. Brown, and T. I. El-Emary
Vol 51
(Z)-Methyl
2-((E)-2-(2-isonicotinoylhydrazono)-4-oxo-3-
7.04 (s, 1H; H-200), 3.83 (s, 3H; OCH3), 2.21 (s, 3H; CCH3). 13C
NMR (DMSO-d6) 175.91 (t, J= 3.9; PhCON), 165.27 (q, J=4.5;
CO2CH3), 163.93 (s; C═N), 161.38 (d, J=5.8; C-100), 143.99
(sextet, J= 6.7; C-4), 138.00 (s; C-300), 137.12 (t, J= 8.6; C-1),
134.01 (dt, Jd = 164.0, Jt =7.0; C-40), 133.50 (t, J=7.6; C-10),
130.19 (dt, Jd = 163.5, Jt =6.6; C-20), 129.65 (ddq, Jd = 162.1, 5.6,
Jq = 5.6; C-3), 128.38 (dd, Jd = 163.7, 7.3; C-30), 127.43 (dd,
J= 165.9, 5.5; C-2), 120.93 (d, J= 173.2; C-200), 52.86
(q, J= 148.4; OCH3), 20.81 (tq, Jt =4.3, Jq = 127.1; CCH3). MS
(EI): m/z (%) = 459 (42), 304 (18), 296 (28), 163 (54), 105 (100),
77 (76), 59 (81). Anal. C20H17N3O6S2 (459.50): Calcd C, 52.28; H,
3.73; N, 9.14; S, 13.96. Found: C, 52.15; H, 3.81; N, 8.99; S, 14.11.
phenylthiazolidin-5-ylidene)acetate (9b).
Pale yellow crystals
(0.260 g, 68%); mp 201–203ꢃC (ethanol). IR (KBr): 3210 (NH),
1
1735, 1695, 1655 (CO), 1610 (C═N), 1590 (Ar-C═C). H NMR
(CDCl3) 9.17 (b, 1H; NH), 8.76 (d, J= 5.6, 2H; H-3), 7.71
(t, J= 5.1, 2H; H-2), 7.37 (t, J= 7.8, 2H; H-30), 7.21 (t, J=7.5, 1H;
H-40), 7.05 (s, 1H; H-200), 6.97 (d, J= 7.6, 2H; H-20), 3.84 (s, 3H;
OCH3). 13C NMR (CDCl3) 165.98 (q, J=4.3; CO2CH3), 163.60
(dt, Jd =4.1, Jt =2.5; C-100), 161.48 (t, J= 5.0; PyCON), 150.80
(bdd, Jd = 182.3, 10.7; C-2), 148.73 (b; C═N), 145.95 (bt; C-10),
138.27 (s; C-300), 137.85 (t, J= 5.9; C-1), 129.62 (dd, J= 161.3, 8.3;
C-30), 125.93 (dt, Jd = 162.7, Jt =8.5; C-40), 121.31 (dddd,
J= 164.7, 7.6, 7.6, 1.9; C-3), 120.96 (ddd, J= 158.7, 7.6, 7.6; C-20),
118.37 (d, J= 173.9; C-200), 52.80 (q, J= 148.2; OCH3). MS (EI):
m/z (%) = 382 (34), 354 (19), 276 (12), 106 (87), 59 (100). Anal.
C18H14N4O4S (382.39): Calcd C, 56.54; H, 3.69; N, 14.65; S, 8.39.
Found: C, 56.39; H, 3.78; N, 14.81; S, 8.25.
(Z)-Methyl
2-((E)-3-allyl-2-(2-benzoylhydrazono)-4-oxo-
thiazolidin-5-ylidene)acetate (9f).
Pale yellow crystals
(0.228 g, 66%), mp 202–204ꢃC (acetonitrile). IR (KBr): 3240 (NH),
1
1720, 1700, 1660 (CO), 1610 (C═N), 1585 (Ar-C═C). H NMR
(DMSO-d6) 11.34 (s, 1H; NH), 7.87 (d, J=6.9, 2H; H-2), 7.60
(t, J= 7.2, 1H; H-4), 7.52 (dd, J=7.4, 7.4, 2H; H-3), 6.82 (s, 1H;
H-200), 5.92 (m, 1H; H-20), 5.221 (d, J= 15.4, 1H; H-30-cis [43]),
5.216 (d, J= 11.2, 1H; H-30-trans [43]), 4.48 (m, 2H; H-10), 3.78 (s,
3H; OCH3). 13C NMR (DMSO-d6) 165.75 (q, J=4.3; CO2CH3),
163.61 (t, J= 3.8; PhCON), 163.29 (dt, Jd =6.3, Jt ~5; C-100),
155.55 (b; C═N), 140.40 (s; C-1), 132.81 (t, J=8.2; C-300), 131.67
(dt, Jd =162.9, Jt = 6.6; C-4), 130.65 (dt, Jd = 159.9, Jt =6.2; C-20),
128.40 (dd, J= 161.9, 7.3; C-3), 127.45 (dm, Jd = 162.1; C-2),
117.56 (ddt, Jd = 154.2, 154.2, Jt =5.7; C-30), 115.20 (dm,
Jd = 172.7; C-200), 52.55 (q, J= 148.2; OCH3), 44.62 (dddt,
Jd = 12.8, 6.4, 6.4, Jt = 143.0; C-10). MS (EI): m/z (%) = 345 (27),
262 (32), 178 (19), 105 (100), 83 (41), 77 (52), 59 (27), 41 (76).
Anal. C16H15N3O4S (345.37): Calcd C, 55.64; H, 4.38; N, 12.17; S,
9.28. Found: C, 55.45; H, 4.48; N, 11.99; S, 9.17.
(Z)-Methyl
2-((E)-4-oxo-3-phenyl-2-(2-tosylhydrazono)-
thiazolidin-5-ylidene)acetate (9c).
Pale yellow crystals
(0.327 g, 76%); mp 220–222ꢃC (acetonitrile). IR (KBr): 3250
1
(NH), 1730, 1695 (CO), 1610 (C═N), 1590 (Ar-C═C). H NMR
(CDCl3) 10.38 (b, 1H; NH), 7.54 (d, J= 8.2, 2H; H-2), 7.52
(t, J= 7.6, 2H; H-30), 7.48 (t, J= 7.1, 1H; H-40), 7.35 (d, J=7.1,
2H; H-20), 7.31 (d, J= 8.1, 2H; H-3), 6.85 (s, 1H; H-200), 3.84
(s, 3H; OCH3), 2.37 (s, 3H; CCH3). 13C NMR (CDCl3) 165.92
(q, J=3.5; CO2CH3), 163.50 (d, J=5.6; C-100), 157.61 (s; C═N),
143.66 (tq, Jt =Jq = 6.6; C-4), 140.90 (d, J=1.0; C-300), 134.79
(t, J= 8.6; C-1), 133.67 (tt, J= 9.3, 2.3; C-10), 129.10 (ddd,
J= 161.3, 5.9, 5.2; C-3), 128.92 (dt, Jd = 162.0, Jt =7.6; C-40),
128.83 (dd, J= 163.5, 7.6; C-30), 127.95 (dd, J= 166.0, 3.5; C-2),
127.90 (ddd, Jd = 165.7, 6.8, 6.8; C-20), 115.48 (d, J= 172.7; C-200),
52.70 (q, J= 148.1; OCH3), 21.00 (tq, Jt =4.2, Jq = 127.1; CCH3).
MS (EI): m/z (%) = 431 (23), 276 (28), 247 (36), 155 (670, 135
(45), 112 (77), 59 (100). Anal. C19H17N3O5S2 (431.49): Calcd C,
52.89; H, 3.97; N, 9.74; S, 14.86. Found: C, 53.08; H, 4.09; N,
9.69; S, 14.78.
(Z)-Methyl
2-((E)-3-allyl-2-(2-isonicotinoylhydra-zono)-4-
oxothiazolidin-5-ylidene)acetate (9g).
Pale yellow crystals
(0.256 g, 74%), mp 194–196ꢃC (acetonitrile). IR (KBr): 3200 (NH),
1
1740, 1700, 1655 (CO), 1605 (C═N), 1590 (Ar-C═C). H NMR
(DMSO-d6) 11.65 (s, 1H; NH), 8.77 (d, J=5.6, 2H; H-3), 7.78
(d, J= 5.4, 2H; H-2), 6.84 (s, 1H; H-200), 5.92 (ddt, Jd = 17.1, 10.4,
Jt =5.2, 1H; H-20), 5.223 (d, J= 16.5, 1H; H-30-cis [43]), 5.216
(d, J= 11.0, 1H; H-30-trans [43]), 4.49 (b, 2H; H-10), 3.79 (s, 3H;
OCH3). 13C NMR (DMSO-d6) 165.74 (q, J=3.5; CO2CH3),
163.32 (t, J= 2.5; PyCON), 163.32 (d, J=5.1; C-100), 155.89
(b; C═N), 140.40 (bs; C-300), 139.79 (quin, J= 3.2; C-1), 130.65
(ddt, Jd = 158.9, 4.3, Jt =4.3; C-20), 121.30 (ddd, J= 161.4, 8.2, 4.1;
C-2), 117.58 (ddt, Jd = 159.8, 154.7, Jt =5.3; C-30), 115.46
(d, J= 172.6; C-200), 52.58 (q, J= 148.2; OCH3), 44.64 (dddt,
Jd = 13.6, 6.3, 6.3, Jt = 142.6; C-10). MS (EI): m/z (%) = 346 (27),
247 (19), 240 (45), 112 (55), 106 (63), 99 (57), 59 (81), 41 (100).
Anal. C15H14N4O4S (346.36): Calcd C, 52.02; H, 4.07; N, 16.18; S,
9.26. Found: C, 51.88; H, 3.98; N, 16.29; S, 9.38.
(Z)-Methyl 2-((E)-3-allyl-4-oxo-2-(2-tosylhydrazono)-thia-
zolidin-5-ylidene)acꢃetate (9d).
Pale yellow crystals (0.312 g,
79%), mp 212–214 C (acetonitrile). IR (KBr): 3200 (NH), 1720,
1
1700 (CO), 1610 (C═N), 1590 (Ar-C═C). H NMR (DMSO-d6)
10.43 (s, 1H; NH), 7.73 (d, J= 8.2, 2H; H-2), 7.43 (d, J=8.1, 2H;
H-3), 6.80 (s, 1H; H-200), 5.72 (ddt, Jd = 17.1, 10.3, Jt =5.5, 1H;
H-20), 5.13 (dd, J= 10.3, 1.1, 1H; H-30-trans [43]), 5.05 (dd,
J= 17.2, 1,2, 1H; H-30-cis [43]), 4.25 (d, J=5.4, 2H; H-10), 3.81 (s,
3H; OCH3), 2.40 (s, 3H; CCH3). 13C NMR (DMSO-d6) 165.72 (q,
J=4.6; CO2CH3), 163.41 (dt, Jd =5.4, Jt =2.7; C-100), 156.56 (b;
C═N), 143.66 (dt, Jd =Jt = 6.8; C-1), 140.35 (s; C-300), 134.89 (t,
J= 7.9; C-4), 130.35 (dddt, Jd = 159.2, 3.3, 3.3, Jt =3.3; C-20),
129.26 (ddq, Jd = 161.8, 5.5, Jq = 5.5; C-3), 127.91 (dd, J= 166.2,
4.9; C-2), 117.91 (dd, Jd = 159.9, 154.9, Jt =5.5; C-30), 115.62 (d,
J= 172.7; C-200), 52.61 (q, J= 148.2; OCH3), 44.61 (dddt, Jd = 13.4,
6.4, 6.1. Jt = 142.7; C-10), 20.96 (tq, Jt =4.2, Jq = 127.1). MS (EI):
m/z (%) = 395 (17), 240 (100), 211 (53), 116 (39), 91 (88), 65 (56).
Anal. C16H17N3O5S2 (395.45): Calcd C, 48.60; H, 4.33; N, 10.63;
S, 16.22. Found: C, 48.44; H 4.42; N, 10.76; S, 16.07.
(Z)-Methyl 2-((E)-3-benzoyl-2-(2-benzoylhydrazono)-4-ox-
othiazolidin-5-ylidene)-acetate (9h).
Pale yellow crystals
(0.311 g, 76%), mp 230–232ꢃC (acetonitrile). IR (KBr): n 3240
(NH), 1745, 1705, 1665 (CO), 1610 (C═N), 1590
(Ar-C═C) cmꢀ1. 1H NMR (DMSO-d6) 11.90 (s, 1H; NH), 8.10 (d,
J=7.3, 2H; H-2), 8.04 (d, J=7.3, 2H; H-20), 7.73 (t, J =7.3, 1H;
H-40), 7.67 (t, J= 7.4, 1H; H-4), 7.64 (dd, J= 7.5, 7.5, 2H; H-30),
7.52 (dd, J= 7.7, 7.7, 2H; H-3), 7.13 (s, 1H; H-200), 3.86 (s, 3H;
OCH3). 13C NMR (DMSO-d6) 176.20 (t, J = 3.9; PhCON), 165.21
(q, J=3.7; CO2CH3), 165.10 [b; (PhCON)0], 163.89 (s; C═N),
161.67 (d, J =5.7; C-100), 137.49 (s; C-300), 134.17 (dt, Jd = 162.8,
Jt = 7.5; C-4), 133.72 (t, J =4.9; C-10), 132.95 (dt, Jd = 158.6,
Jt =7.2; C-40), 130.66 (t, J= 7.7; C-1), 129.71 (ddd, J= 162.6, 6.6,
(Z)-Methyl
2-((E)-2-(benzoylimino)-3-(4-methylbenzene-
Pale
sulfonamido)-4-oxothiazolidin-5-ylidene)acetate (9e).
yellow crystals (0.325 g, 71%), mp 237–239ꢃC (acetonitrile). IR
(KBr): 3265 (NH), 1745, 1700, 1665 (CO), 1620 (C═N), 1595
(Ar-C═C). 1H NMR (DMSO-d6) 11.47 (b, 1H; NH), 7.90 (dd,
J=7.2, 1.1, 2H; H-20), 7.75 (d, J=8.3, 2H; H-2), 7.68 (t, J=7.4,
1H; H-40), 7.48 (d, J= 7.8, 2H; H-30), 7.21 (d, J=8.1, 2H; H-3),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2014
A Facile Method for the Synthesis of Hydrazine-4-oxothiazolidine and
49
Imino-5-oxothiadiazine Derivatives from 1,4-Disubstituted Thiosemicarbazides
6.6; C-2), 128.86 (dd, J= 162.8, 7.3; C-3/30), 128.82 (dd, J= 163.1,
7.5; C-30/3), 127.80 (ddd, J= 161.7, 6.7, 6.7; C-20), 121.36 (d,
J= 173.5; C-200), 52.55 (q, J= 148.4; OCH3). MS (EI): m/z
(%) = 409 (32), 275 (23), 163 (41), 114 (19), 105 (100), 77 (62),
59 (48). Anal. C20H15N3O5S (409.42): Calcd C, 58.67; H, 3.69; N,
10.26; S, 7.83. Found: C, 58.79; H, 3.58; N, 10.41; S, 7.98.
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Acknowledgment. Purchase of an NMR spectrometer was assisted
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet