Reaction of arylidenehydrazono-4-aryl-2,3-dihydrothiazole-5-carbonitriles with diethyl acetylenedicarboxylate. Synthesis of (Z)-ethyl 2-[((Z)-2-(E)- arylidenehydrazono)-4-oxo-thiazolidine-5-ylidene]acetates. NMR investigation

Article abstract of DOI:10.1080/17415993.2014.882337

(Z)-Ethyl 2-[((Z)-2-(E)-arylidenehydrazono)-4-oxo-thiazolidine-5-ylidene] acetates were synthesized by three different methods: (a) reaction of arylidenehydrazono-4-aryl-2,3-dihydrothiazole-5-carbonitriles with diethyl acetylenedicarboxylate (DEAD) in acetic acid with prolonged reflux, (b) reaction between thiosemicarbazones, 2-arylidenemalononitriles and DEAD under conventional conditions or microwave irradiation, (c) one-pot three-component reaction of thiosemicarbazone derivatives, ylidene and DEAD. The thiazolinone adducts were obtained in good to excellent yields. NMR of the obtained products was investigated.

Full text of DOI:10.1080/17415993.2014.882337

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Reaction of arylidenehydrazono-4-
aryl-2,3-dihydrothiazole-5-carbonitriles
with diethyl acetylenedicarboxylate.
Synthesis of (Z)-ethyl 2-[((Z)-2-
(E)-arylidenehydrazono)-4-oxo-
thiazolidine-5-ylidene]acetates. NMR
investigation
Ashraf A. Alya, Esam A. Ishaka & Alan B. Brownb
a Chemistry Department, Faculty of Science, Al Jouf University,
Sakaka, Al Jouf, KSA
b Chemistry Department, Florida Institute of Technology,
Melbourne, FL 32901, USA
Published online: 12 Feb 2014.
To cite this article: Ashraf A. Aly, Esam A. Ishak & Alan B. Brown (2014) Reaction of
arylidenehydrazono-4-aryl-2,3-dihydrothiazole-5-carbonitriles with diethyl acetylenedicarboxylate.
Synthesis of (Z)-ethyl 2-[((Z)-2-(E)-arylidenehydrazono)-4-oxo-thiazolidine-5-ylidene]acetates. NMR
investigation, Journal of Sulfur Chemistry, 35:4, 382-393, DOI: 10.1080/17415993.2014.882337
To link to this article: http://dx.doi.org/10.1080/17415993.2014.882337
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Journal of Sulfur Chemistry, 2014
Vol. 35, No. 4, 382–393, http://dx.doi.org/10.1080/17415993.2014.882337
Reaction of arylidenehydrazono-4-aryl-2,3-dihydrothiazole-
5-carbonitriles with diethyl acetylenedicarboxylate. Synthesis of
(Z)-ethyl 2-[((Z)-2-(E)-arylidenehydrazono)-4-oxo-thiazolidine-
5-ylidene]acetates. NMR investigation
Ashraf A. Alya†,∗, Esam A. Ishaka‡ and Alan B. Brownb
aChemistry Department, Faculty of Science, Al Jouf University, Sakaka, Al Jouf, KSA;
bChemistry Department, Florida Institute of Technology, Melbourne, FL 32901, USA
(Received 5 November 2013; accepted 8 January 2014)
(Z)-Ethyl 2-[((Z)-2-(E)-arylidenehydrazono)-4-oxo-thiazolidine-5-ylidene]acetates were synthesized by
three different methods: (a) reaction of arylidenehydrazono-4-aryl-2,3-dihydrothiazole-5-carbonitriles
with diethyl acetylenedicarboxylate (DEAD) in acetic acid with prolonged reflux, (b) reaction between
thiosemicarbazones, 2-arylidenemalononitriles and DEAD under conventional conditions or microwave
irradiation, (c) one-pot three-component reaction of thiosemicarbazone derivatives, ylidene and DEAD.
The thiazolinone adducts were obtained in good to excellent yields. NMR of the obtained products was
investigated.
Keywords: thiosemicarbazones; thiazolidine; diethyl acetylenedicarboxylate; new conversion; NMR
1. Introduction
Thiazolidin-4-ones are important heterocyclic compounds owing to their biological activities,[1,2]
such as anti-tuberculosis,[3] anti-convulsant,[4] and fungistatic.[5] Reactions of dimethyl
∗Corresponding author. Email: ashrafaly63@yahoo.com
†Permanent address: Chemistry Department, Faculty of Science, El-Minya University, 61519-El-Minya, Egypt.
‡Permanent address: Chemistry Department, Faculty of Science, Al-Azhar University, Assuit, Egypt.
© 2014 Taylor & Francis

Journal of Sulfur Chemistry 383
acetylenedicarboxylate (DMAD) with esters and amides of dithiocarboxylic acids are well-known
methods for preparation of five-membered S- and S, N-heterocycles.[6,7] Thioureas react with
DMAD to give 1:1 adducts with loss of methanol.[7] In the past, several methods have been
reported for the preparation of thiazolidinone derivatives. For example, the reaction of thioamides
or thiosemicarbazide derivatives with dialkyl acetylenedicarboxylates is a convenient and effec-
tivemethodtoprepare2-amino-5-methoxycarbonyl-thiazolidin-4-ones.[8,9]Thiosemicarbazones
[10–14] and their metal complexes have a broad range of biological applications and medicinal
properties, including antiviral, antimalarial, antifungal, and antitumor activity.[15–26] Rakitin
reported that an anthraquinonothiazole derivative reacted with triethylamine to give a fused pyr-
role derivative.[27] Also, 2-(dimethylamino)-thiazole reacted with DMAD to produce a pyridine
derivative via extrusion of a sulfur atom.[28] In recent years, the use of microwave irradiation
has become popular among synthetic organic chemists, both to improve classic organic reac-
tions (shortening reaction times and/or improving yield), and to promote new reactions.[29] Aly
et al. demonstrated a very convenient procedure to synthesize 1,3-thiazines by the reaction of
but-2-ynedioic acid, propynoic acid ethyl ester, and (E)-1,4-diphenyl-but-2-ene-1,4-dione with
aroyl-substituted thioureas in acetic acid.[30] The same group [31] changed the conditions of the
reaction by mixing a solution of DEAD and aroylthioureas together with triphenyl phosphine. The
products were identified as methyl-(2Z)-2-[(2Z)-2,3-diaryl-carbonylimino-4-oxo-thiazolidin-5-
ylidene]-acetates. Hence, in this paper, we describe the action of DEAD on the thiazole ring
(which results from reaction of thiosemicarbazones with 2-arylidenemalononitriles). The one-
step three-component system, including thiosemicarbazones, ylidene and DEAD seems to offer
an alternative fast and attractive green methodology that saves both solvent and time compared
with the multi-step approach.
2. Results and discussion
Recently, we reported the synthesis of arylidenehydrazono-4-aryl-2,3-dihydrothiazole-5-carboni-
triles3a–jbythereactionofpyridinesolutionsofequimolaramountsof(E)-2-arylidenehydrazine-
carbothioamides 1a–j and arylidenemalononitriles 2 under gentle heating (60–80◦C) or under
microwave irradiation (Scheme 1).[32]
Trials using solvents such as DMF, ethanol/piperidine, ethanol/Et3N, dioxane/piperidine,
DMSO, or solvent-free fusion all failed. It is noteworthy that reactions between 1a–j and 2 in
acetic acid produced low yields of products 3a–j (Scheme 1). Surprisingly, on reacting compounds
3a–j with diethyl acetylenedicarboxylate (DEAD, 4) in acetic acid under prolonged reflux, the
reaction produced (Z)-ethyl 2-[((Z)-2-(E)-arylidenehydrazono))-4-oxo-thiazolidine-5-ylidene]-
acetates 5a–e together with 3-aryl-propiolonitriles 6a–d (Scheme 2). The sequence indicated
opening of the thiazolidine ring in 3a–j during its reaction with DEAD (4; Scheme 3).
A plausible rationale for the reaction (Scheme 3) begins with attack on the C≡C bond by the S-
lone pair to form the salt 7. Neutralization of 7 would cause elimination of 3-aryl-propiolo-nitriles
6 and intermediate 8 (Scheme 3). Tautomerism of 8 into 9 would enable the amidine nitrogen in
9 to attack the carbonyl ester leading to the new thiazolidinone 5 accompanied with elimination
of ethanol molecule aided by proton transfer (Scheme 3). In order to prepare 5a–f, we reacted
methanolic solutions of thiosemicarbazones 1a–f with DEAD 4 under reflux. The synthesis was
also achieved by mixing the two starting materials without solvent and exposing the mixture to
microwave irradiation. The latter method gave higher yields of the products 5a–f (Scheme 4).
The third method constitutes a facile synthesis of compounds 5a and 5b. It is a one-pot three-
component reaction of a mixture of equimolar quantities of thiosemicarbazones 1a, b with 2a, b
and 4 under prolonged reflux in acetic acid (Scheme 5). We expected that compounds 1 would

384 A.A. Aly et al.
Scheme 1. Synthesis of thiazolidines 3a–j.
Scheme 2. Conversion of thiazolidines 3a–j into thiazolidinones 5a–e.
react more readily with 4 than with 2. We reacted compounds 1 with 2, and then in the same
reaction vessel we added compound 4 without separation of intermediate compounds 3. Since,
as mentioned before, the reaction of 1 and 2 in acetic acid gave relatively low yield percentages
of products 3 [32] that would decrease the overall yields of compounds 5. Reaction of 1a,b, 2a,b
and 4 in pyridine and/or under microwave irradiation failed.
The structures of compounds 5a–f were elucidated on the basis of IR, NMR and mass spectra
together with elemental analyses. The NMR data of the product obtained from the reaction of

Journal of Sulfur Chemistry 385
Scheme 3. Plausible mechanism describing formation of thiazolidinones 5.
Scheme 4. Synthesis of thiazolidinones 5a–f.
3a with 4 are summarized in Tables 1 and 2. The ethoxy carbons and protons are assigned
straightforwardly: CH2 CH3, δC = 13.93; CH2CH3, δH = 1.28; CH2CH3, δC = 61.25; CH2CH3,
δH = 4.26. One carbonyl carbon (δC = 165.35) gives HMBC correlation with CH2CH3, and
is assigned as CO2CH2CH3. The other carbonyl (δC = 165.63) is broadened, presumably due
to amidine tautomerism; it is assigned as C-4, and gives HMBC correlation with the vinylic
CH at δH = 6.66, assigned as H-6. H-6 gives HSQC correlation with δC = 114.48 and HMBC
correlation with δC = 142.66, assigned as C-6 and C-5, respectively. The singlet at δH = 8.55 is
=
=
=
assigned as CH N; the attached carbon at δC = 158.62 is assigned as CH N. CH N also gives
HMBC correlation with a signal at δC = 133.60, assigned as C-i, and a signal at δC = 127.93,

386 A.A. Aly et al.
Scheme 5. One-pot synthesis of thiazolidinones 5a, b.
Table 1. The 1H NMR spectral data of the product from
the reaction of 3a with 4.
1H NMR (DMSO-d6)
COSY
Assignment
12.90 (b; 1H)
8.55 (s; 1H)
N–H
=
CH
H-o
N
7.83 (dd, J = 6.6, 2.9 Hz; 2H)
7.52
7.83
7.52 (m; 3H)
H-m, H − p
6.66 (s; 1H)
H-5
4.26 (q, J = 7.1; 2H)
1.28
4.26
CH2CH3
CH2CH3
1.28 (t, J = 7.1; 3H)
Table 2. The 13C NMR spectral data of the product from the reaction of 3a with 4.
13C NMR (DMSO-d6)
HSQC
HMBC
Assignment
165.63 (dd, J = 9.0, 4.9 Hz)
165.35 (dt, Jd = 1.4, Jt = 2.8 Hz)
160.26 (“q”, J = 5.7 Hz)
6.66
4.26
8.55
7.85
6.66
8.55
7.83
7.52
8.55
C-4
CO2CH2CH3
C-2
=
158.62 (dt, Jd = 166.2, Jt = 2.9 Hz)
142.66 (s)
8.55
CH N
C-5
C-i
133.60 (t, J = 7.4 Hz)
131.18 (dt, Jd = 161.1, Jt = 5.5 Hz)
128.86 (ddd, J = 164.6, 3.6, 3.6 Hz)
127.93 (dddd, J = 160.2, 7.4, 3.7, 3.7 Hz)
114.48 (d, J = 171.2 Hz)
7.52
7.52
7.83
6.66
4.26
1.28
C-p
C-m
C-o
C-6
61.25 (tq, Jt = 148.6, Jq = 4.4 Hz)
13.93 (tq, Jt = 2.5 Hz, Jq = 127.1)
1.28
4.26
CO2CH2CH3
CH3
assigned as C-o. The protons attached to C-o appear at δH = 7.83; they give HMBC correlation
with a signal at δC = 131.18, assigned as C-p. The proton attached to C-p appears at δH = 7.52
along with the remaining two aromatic protons, assigned as H-m; the remaining aromatic carbons
appear at δC = 128.86, and are assigned as C-m. The remaining signal at δC = 160.26 is assigned
=
as C-2; like C-i, this signal gives HMBC correlation with CH N.
1
To distinguish between possibilities 5a and 10a (Figure 1), a H-coupled 13C spectrum was
=
collected. The amide C O shows doublet couplings of 9.0 and 4.9 Hz, consistent with three-
=
bond coupling to H-6 and two-bond coupling to N-H. The ester C O shows doublet coupling of
1.4 Hz, consistent with two-bond coupling to H-6, and triplet coupling of 2.8 Hz, consistent with
=
four-bond coupling to CH2CH3. C-6 shows no coupling at all. In 10a, the amide C O would be
=
two bonds from H-6 and the ester C O would be three bonds from H-6, which should reverse
the sizes of the observed couplings. In α, β-unsaturated carbonyl compounds, two-bond coupling
=
=
constants between C O and H-α are smaller (3–6 Hz) than three-bond couplings between C O
=
and H-β(8–16 Hz).[33] The observations that amide C O shows coupling to N-H, but C-5 and
C-6 do not, also support structure 5a over isomer 10a. The observation of coupling between amide

Journal of Sulfur Chemistry 387
Figure 1. Structures of possible products from the reaction of 3a–d with 2.
Table 3. 1H NMR spectral data of 5b.
1H NMR (DMSO-d6)
COSY
Assignment
12.83 (b)
8.49 (s, 1H)
7.71 (d, J = 7.9; 2H)
7.31 (d, J = 7.8; 2H)
6.63 (s, 1H)
N–H
=
7.71
8.49, 7.31
7.71, 2.37
CH
H-o
H-m
N
H-6
4.25 (q, J = 7.1 Hz; 2H)
1.28
7.31
4.26
CH2CH3
Ar-CH3
CH2-CH3
2.37 (s, 3H)
1.28 (t, J = 7.1 Hz; 3H)
Table 4. 13C NMR spectral data of 5b.
13C NMR (DMSO-d6)
HSQC
HMBC
Assignment
165.69 (dd, J = 9.9, 4.4)
165.45 (s)
6.66
4.26
C-4
CO2CH2CH3
C-2
161.20 (t, J = 3.3)
=
157.39 (dt, Jd = 167.5, Jt = 4.6)
8.56
7.59
7.85
6.66
7.85,
CH N
C-5
142.80 (s)
C-p
135.73 (tt, J = 11.3, 9.0)
132.62 (dt, Jd = Jt = 8.5)
129.59 (ddd, J = 163.7, 6.7, 3.5)
8.56,
8.56,
7.59
C-i
C-o
C-m
C-6
CH2CH3
CH2CH3
7.59
7.85
7.85
7.59
6.66
4.26
1.28
129.09 (dd, J = 167.5, 4.6)
114.54 (d, J = 171.4)
61.32 (tq, Jt = 148.6, Jq = 4.5)
14.00 (tq, Jt = 2.7, Jq = 126.9)
1.28
4.26
=
C O and N-H also excludes isomer 13a, in which this would be a five-bond coupling. Structure
13
=
13a can be excluded via C chemical shifts: structures 5 and 10–12 each have two C O and
=
=
=
=
two C N; 13a would have two C O, one C N, and one C S. Thiocarbonyls typically resonate
ꢀꢀ
=
at δC > 180 ppm (cf. tetramethylthiourea 194.8 [34]); in 5b , all four C X appear between
δC = 157–165, so the structure of 13bꢀꢀ is eliminated.
Tables 3 and 4 summarize the NMR data of 5b. The DEAD-derived signals are assigned by
the same logic used for 5a: CH2CH3, δC = 14.00; CH2CH3, δH = 1.28; CH2CH3, δC = 61.29;
CH2CH3, δH = 4.25; CO2CH2CH3, δC = 165.44; C-4, δC = 165.85; H-6, δH = 6.63; C-6,

388 A.A. Aly et al.
Table 5. 1H NMR spectral data of 5d.
1H NMR (DMSO-d6)
COSY
Assignment
12.94 (b; 1H)
8.56 (s; 1H)
7.85 (d, J = 4; 2H)
7.59 (d, J = 8.4; 2H)
6.66 (s; 1H)
N–H
=
CH
H-o
N
7.59
7.85
H-m
H-6
4.26 (q, J = 7.1; 2H)
1.28
4.26
CH2CH3
CH2CH3
1.28 (t, J = 7.1; 3H)
Table 6. 13C NMR spectral data of 5d.
13C NMR (DMSO-d6)
HSQC
HMBC
Assignment
165.85 (d, J = 5.3 Hz)
165.44 (s)
160.03 (s)
6.63
4.25
C-4
CO2CH2CH3
C-2
8.49
8.49
6.63
=
158.53 (dt, Jd = 164.6, Jt = 4.1 Hz)
7.71
CH N
142.93 (s)
C-5
C-p
C-i
141.29 (tq, Jt = Jq = 6.8Hz)
7.71,2.37
8.49,7.31
7.31,2.37
8.49, 7.71
131.03 (dt, Jd = Jt = 7.8 Hz)
C-m
C-o
C-6
CH2CH3
Ar-CH3
CH2CH3
129.53 (ddd, J = 152.9, 5.5, 5.5 Hz)
6.63
4.25
2.37
1.28
128.00 (ddd, J = 154.1, 5.7, 4.1 Hz)
1.28
7.31
4.25
114.33 (d, J = 171.2)
61.25 (tq, Jt = 148.7, Jq = 4.4 Hz)
21.15 (tq, Jt = 4.2, Jq = 126.8 Hz)
14.00 (tq, Jt = 2.5, Jq = 126.9 Hz)
δC = 114.33; C-5, δC = 142.93. C-4 gives a doublet coupling, presumably to H-6. The ben-
zylic methyl carbon and protons appear at δC = 21.15 and δH = 2.37, respectively; the benzylic
protons give HMBC correlation with the carbons at δC = 141.29 and 129.53, and the benzylic
carbon gives HMBC correlation with the protons at δH = 7.31, which in turn give HSQC correla-
tion with δC = 129.53. This group of correlations leads to assignment of δC = 141.29 and 129.53
as C-p and C-m, respectively, and of δH = 7.31 as H-m.
The other aromatic protons at δH = 7.71 are assigned as H-o, and the attached carbons at
δC = 128.00 are assigned as C-o. C-o gives HMBC correlation with a singlet at δH = 8.49,
=
=
=
assigned as CH N; the attached carbon at δC = 158.53 is assigned as CH N. CH N also
gives HMBC correlation with a signal at δC = 131.03, assigned as C-i. The remaining signal at
δC = 160.03 is assigned as C-2.
Tables 5 and 6 summarize the NMR data of product 5d. Again, the ethoxy carbons and
protons are assigned straightforwardly: CH2CH3, δC = 14.00; CH2CH3, δH = 1.28; CH2CH3,
δC = 61.32; CH2CH3, δH = 4.26. One carbonyl carbon (δC = 165.45) gives HMBC correlation
with CH2CH3, and is assigned as CO2CH2CH3. The other carbonyl (δC = 165.69) is broadened,
presumably due to amidine tautomerism; it is assigned as C-4, and gives HMBC correlation with
the vinylic CH at δH = 6.66, assigned as H-6. HSQC correlation with δC = 114.54 and HMBC
correlation with δC = 142.80, assigned as C-6 and C-5, respectively.The singlet at 8.56 is assigned
=
=
=
as CH N; the attached carbon at δC = 157.39 is assigned as CH N. CH N also gives HMBC
correlation with a signal at δC = 132.62, assigned as C-i, and a signal at δC = 129.59, assigned
as C-o. The protons attached to C-o appear at δH = 7.85; they give HMBC correlation with the
“other” C-o and also with a signal at δC = 135.73, assigned as C-p. The remaining aromatic

Journal of Sulfur Chemistry 389
Figure 2. Fragmentation patterns of peak ions in compound 5d.
carbons and protons appear at δC = 129.09 and δH = 7.59, and are assigned as C-m and H − m,
respectively; C-m gives HMBC correlation with the “other” H-m, and H-m also gives HMBC
correlation with C-i and C-p.
The remaining signal at δC = 161.20 is assigned as C-2; like C-4, this signal is broadened by
amidine tautomerism. In the 1H-coupled 13C spectrum, the amide C O shows doublet couplings
=
of 9.9 and 4.4 Hz, consistent with three-bond coupling to H-6 and two-bond coupling to N-H.
=
Neither the ester C O nor C-5 shows any coupling at all.
The mass spectrum of 5d contained fragments at m/z = 337 (M+; 100%), 226 (68%), 138
(70%) and 103 (100). Figure 2 shows possible fragmentation pathways. These peaks are repeated
in the mass spectra of compounds 5a–f.
Products isolated from the reaction of compounds 3a–j with 4 gave the same physical, spectral
and analytical analyses as those isolated from other methods.Yields of products were higher when
the aromatic moiety bore electron donating groups such as methyl or methoxy, than when sub-
stituents were electron-withdrawing (e.g. chloro) in 3c. Moreover, the reaction can be generalized
to heterocyclic rings as in 3j.
3. Conclusion
In conclusion, we have synthesized a new series of thiazole derivatives in nearly quantitative yields
using conventional and microwave-assisted synthetic pathways. A one-pot three-component syn-
thesis could be used under conventional conditions, but was found to be limited under microwave
assistance.
4. Experimental
Benzaldehyde, p-methylbenzaldehyde, p-methoxy-benzaldehyde, p-chlorobenzaldehyde, furan-
2-carboxyaldehyde, 2-acetylpyridine, thiosemicarbazide, methanol, pyridine, DEAD, and all the
solvents such as ethyl acetate and ethanol were purchased from Merck Chemical Co. and were used
without further purification. TLC was performed on analytical Merck 9385 silica aluminum sheets
(Kieselgel 60) with PF254 indicator. TLCs were viewed under ν = 254 nm. Melting points (mp)
weredeterminedonaStuartelectrothermalmeltingpointapparatusandareuncorrected. IRspectra
were recorded as KBr disks on a Shimadzu-408 infrared spectrophotometer, Faculty of Science,
El Minia University. NMR spectra were measured on a Bruker AV-400 spectrometer (400 MHz
for 1H, 100 MHz for 13C) at Florida Institute of Technology, or in the NMR Laboratory Center,
Assiut University, Assiut, Egypt. Electron impact mass spectra were recorded with a JEOL JMS-
600 spectrometer at an ionization voltage of 70 eV at the Central Lab, Assiut University, and the
Microanalytical Center, Faculty of Science, Cairo University, Cairo, Egypt. Thiosemicarbazones
1a–j were prepared according to the literature.[35]

390 A.A. Aly et al.
4.1. General procedure
4.1.1. Method 1: Reactions of thiazolidines 3a–j with DEAD4; synthesis of
(arylidenehydrazono-4-oxo-thiazolidin-5-ylidene) acetic acid ethyl esters 5a–e
A solution of equimolar amounts of 3a–j (2 mmol) and DEAD, 4 (2 mmol) in acetic acid (50 mL)
was heated under reflux at for 8–10 h. The reaction was followed by TLC analysis. The mixture
was cooled to room temperature and the precipitate was filtered off to produce 5a–e. The mother
liquor was concentrated to produce compounds 6a–d. The products 5a–e were recrystallized from
appropriate solvents.
Compounds 6a–c were identified from their physical properties: 6a (0.025 g, 10%), 3-
phenylpropynenitrile, dark yellow solid, mp 38–40◦C (lit. [36] 39◦C); 6b (0.03 g, 12%),
3-(4ꢀ-methylphenyl)propynenitrile, mp 63◦C (lit. [36] 60–62◦C); 6c (0.04 g, 15%) 3-(4-
methoxyphenyl)propynenitrile, mp 77◦C (lit. [36] 76–78◦C); 6d (0.025 g, 8%), 3-(4ꢀ-
chlorophenyl)propynenitrile, mp = 85–86◦C (lit. [37] 83–85◦C).
4.1.2. Method 2: Reactions of thiosemicarbazones 1a–f with DEAD 4; synthesis of 5a–f under
conventional condition
A mixture of 1a–f (2 mmol) and 4 (2 mmol) in MeOH was stirred at reflux for 3–5 h. The mixture
was cooled to room temperature; the precipitate was filtered off and the product was recrystallized
from the solvent indicated.
4.1.3. Synthesis of 5a–f under microwave irradiation
A mixture of 1a–f (2 mmol) and 4 (2 mmol) in a beaker was placed in a domestic microwave
oven (SUNFLAME) and irradiated at 190W for 5–10 min. Then, the mixture was cooled to
room temperature; the solution was poured into 100 mL of ice water and mixed thoroughly, then
allowed to stand for 15 min. The precipitate obtained was filtered, washed with cold ethanol, and
recrystallized from the solvent indicated.
4.1.4. Method 3: Reaction of thiosemicarbazones 1a, b with 2 and DEAD 4; one-pot synthesis
of 5a, b
A solution of equimolar amounts of 1a, b,2, and 4 (2 mmol) in acetic acid (75 mL) was heated
under reflux for 12–18 h. The reaction was followed by TLC analysis. The mixture was cooled
to room temperature and the precipitate was filtered off to produce 5a–e. The mother liquor was
concentrated to produce compounds 6a, b. Yields of products 5a–f reported from microwave
conditions refer to in Method 2.
4.1.5. [4-Oxo-2-(benzylidene)hydrazono)thiazolidine-5-ylidine]acetic acid ethyl ester (5a)
Yellow crystals (ethanol), yield 0.50 g (82%), mp 220◦C. IR (KBr) (λmax, cm−1): 3080 (Ar-CH),
1
=
=
=
=
2760 (CH ), 1740, 1715 (2 C O), 1660, 1634, 1600, 1580 (C N, C C). H NMR (400 MHz,
DMSO-d6): Table 1. 13C NMR (100 MHz, DMSO-d6): Table 2. MS (70 eV, %), m/z: 303 (M+,
100), 288 (22), 274 (30), 258 (36), 226 (56), 202 (16), 138 (54), 103 (100), 98 (50), 76 (30). Anal.
Calcd for C14H13N3O3S: C, 55.43; H, 4.32; N, 13.85%. Found; C, 55.40; H, 4.30; N, 14.00%.

Journal of Sulfur Chemistry 391
4.1.6. [4-Oxo-2-(4ꢀ-methylbenzylidene)-hydrazono)thiazolidine-5-ylidine]acetic acid ethyl
ester (5b)
Yellow crystals (methanol), yield 0.53 g (86%), mp 180◦C. IR (KBr) (λmax, cm−1): 3090 (Ar-
1
=
=
=
CH), 2080 (Aliph-CH), 1742, 1717 (2 C O), 1660, 1632, 1600, 1560 (C N, C C). H NMR
(400 MHz, DMSO-d6): Table 3. 13C NMR (100 MHz, DMSO-d6): Table 4. MS (70 eV, %), m/z:
317 (M+, 100), 302 (26), 288 (20), 274 (28), 226 (54), 202 (20), 138 (56), 103 (100), 98 (52), 76
(28). Anal. Calcd for C15H15N3O3S: C, 56.77; H, 4.76; N, 13.24%. Found; C, 56.60; H, 4.60; N,
13.30%.
4.1.7. [4-Oxo-2-(4ꢀ-methoxybenzylidene)-hydrazono-5-ylidine)thiazolidine-5-ylidine]acetic
acid ethyl ester (5c)
Yellow crystals (ethanol), yield 0.43 g (90%), mp 140–142◦C. IR (KBr) (λmax, cm−1): 3075 (Ar-
1
=
=
=
CH), 2090–2060 (Aliph-CH), 1740, 1715 (2 C O), 1658, 1630, 1600, 1560 (C N, C C). H
=
NMR (400 MHz, DMSO-d6): 12.86 (b, 1H, N-H), 8.50 (s, 1H, CH N), 7.90 (dd, J = 6.7, 2.7 Hz;
2H, H-o), 7.04 (m; 2H, H-m), 6.25 (s, 1H, H-6), 4.20 (q, J = 7.0 Hz; 2H, CH2CH3), 3.90 (s,
CH3), 1.35 (t, J = 7.1 Hz; 3H, CH2CH3). 13C NMR (100 MHz, DMSO-d6): 167.00 (C-4), 165.35
=
(CO2CH2CH3), 162.00 (s, C-i, Ar-C-OCH3), 160.26 (C-2), 158.62 (CH N), 142.66 (s, C-5),
133.60 (C-i), 128.20 (C-m), 114.00 (C-o), 114.48 (C-6), 61.20 (CH2CH3), 55.40 (s, Ar-OCH3)
13.93 (CH2CH3). MS (70 eV, %), m/z: 333 (M+, 100), 318 (40), 302 (46), 272 (34), 258 (30),
226 (58), 138 (64), 103 (98), 98 (62), 76 (30). Anal. Calcd for C15H15N3O4S: C, 54.04; H, 4.54;
N, 12.60%. Found; C, 53.90; H, 4.40; N, 12.50%.
4.1.8. [4-Oxo-2-(4ꢀ-chlorobenzylidene)-hydrazono)thiazolidine-5-ylidine]acetic acid ethyl
ester (5d)
Yellow crystals (ethyl acetate), yield 0.53 g (79%), mp 240◦C. IR (KBr) (λmax, cm−1): 3060
1
=
=
=
(Ar-CH), 1740, 1715 (2 C O), 1660, 1630, 1600, 1558 (C N, C C). H NMR (400 MHz,
DMSO-d6): Table 5. 13C NMR (100 MHz, DMSO-d6): Table 6. MS (70 eV, %), m/z: 339 (M+2
,
40), 338 (M+1, 40), 337 (M+, 100), 226 (68), 141 (36), 138 (70), 124 (80), 103 (100), 78 (44).
Anal. Calcd for C14H12ClN3O3S: C, 49.78; H, 3.58; Cl, 10.50; N, 12.44%. Found; C, 49.62; H,
3.65; Cl, 10.40; N, 12.30%.
4.1.9. [4-Oxo-2-(furan-2-ylmethylene)hydrazono)thiazolidine-5-ylidine]-acetic acid ethyl
ester (5e)
Pale yellow crystals (acetone), yield 0.41 g (70%), mp > 260◦C. IR (KBr) (λmax, cm−1): 3080
1
=
=
=
(Ar-CH), 1740, 1715 (2 C O), 1660, 1630, 1600, 1562 (C N, C C), 1110 (C–O). H NMR
=
(400 MHz, DMSO-d6): 12.80 (b; 1H, N–H), 8.50 (s; 1H, CH N), 7.75 (dd, J = 6.6, 2.9 Hz;
1H, furan-H-5), 7.00 (m, 1H, furan-H-3), 6.60 (s, 1H, H-6), 6.50 (m, 1H, furan-H-4), 4.20
(q, J = 7.4 Hz; 2H, CH2CH3), 1.28 (t, J = 7.1 Hz; 3H, CH2CH3). 13C NMR (100 MHz, DMSO-
=
d6): 165.80 (C-4), 165.40 (s, CO2CH2CH3), 160.00 (s, C-2), 158.50 (CH N), 150.00 (C-2-furan,
C-i), 144.00 (C-5-furan-C-i), 142.90 (s, C-6), 120.00 (CH-3-furan), 114.30 (C-5), 113.00 (CH-
4-furan), 61.30 (CH2CH3), 14.20 (CH2CH3). MS (70 eV, %), m/z: 293 (M+, 100), 227 (66), 141
(40), 124 (76), 102 (100), 78 (30). Anal. Calcd for C12H11N3O4S: C, 49.14; H, 3.78; N, 14.33%.
Found; C, 49.00; H, 3.65; N, 14.30%.

392 A.A. Aly et al.
4.1.10. [4-Oxo-2-(pyridine-2-ylethylidene)hydrazono)thiazolidine-5-ylidine]-acetic acid ethyl
ester (5f)
Orange crystals (ethyl acetate), yield 0.47 g (74%), mp = 198◦C. IR (KBr) (λmax, cm−1): 3095
1
=
=
=
(Ar-CH), 2060 (Aliph-CH), 1740, 1715 (2 C O), 1668, 1660, 1632, 1600, 1550 (C N, C C). H
NMR (400 MHz, DMSO-d6): 12.84 (b, 1H, N–H), 8.70 (dd, 1H, J = 7.4, 1.2 Hz, pyridine-H-6),
8.00 (dd, 1H, J = 7.4, 1.2 Hz, pyridine-H-3), 7.80 (m, 1H, pyridine-H-4), 7.60 (m, 1H, pyridine-
H-5), 6.60 (s, 1H, H-6), 4.30 (q, J = 7.1 Hz; 2H, CH2CH3), 2.80 (s, CH3),1.30 (t, J = 7.1 Hz;
3H, CH2CH3). 13C NMR (100 MHz, DMSO-d6): 166.00 (C-4), 165.40 (s, CO2CH2CH3), 164.00
(pyridine-C-CH3), 162.00 (s, C-2), 155.00 (pyridine-Ci-2), 148.50 (pyridine-CH-6), 140.00 (C-
6), 136.8 (pyridine-CH-4), 127.00 (pyridine-CH-5), 123.00 (pyridine-CH-3), 114.00 (C-5), 60.00
(CH2CH3), 14.00 (CH3), 15.00 (CH2CH3). MS (70 eV, %), m/z: 318 (M+, 100), 302 (14), 240
(24), 226 (60), 141 (38), 124 (74), 102 (100), 80 (34). Anal. Calcd for C14H14N4O3S: C, 52.82;
H, 4.43; N, 17.60%. Found; C, 52.65; H, 4.55; N, 17.72%.
Funding
Authors express all the gratitude and thanks to the University of Al Jouf University – Kingdom of Saudi Arabia for its
financial and effective support to the project submitted. The NMR spectrometer at Florida Institute of Technology was
purchased with the aid of the National Science Foundation (CHE 03-42251).
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