A facile strategy for the annulation of 2-phenylsulfonyl methylene thiazolidin-4-one via multicomponent reactions

Article abstract of DOI:10.1016/j.crci.2012.11.002

An efficient synthesis of 5-amino-7-aryl-3-oxo-8-(phenylsulfonyl)- thiazolo[3,2-a]pyridine-6-carbonitriles was conducted utilizing multicomponent condensation reaction of malononitrile, aromatic aldehydes and 2-phenylsulfonylmethylenethiazolidin-4-one in one pot. Depending on the equivalence of the aldehyde, two different products were obtained from moderate to excellent yields. Thirteen novel structures were characterized by physical and spectroscopic methods (m.p., Rf, IR, NMR and mass analysis).

Full text of DOI:10.1016/j.crci.2012.11.002

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C. R. Chimie xxx (2012) xxx–xxx
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Full paper/Memoire
A facile strategy for the annulation of 2-phenylsulfonyl methylene
thiazolidin-4-one via multicomponent reactions
*
Cevher Altug˘ , Esra Caner
Department of Chemistry, Abant Izzet Baysal University, 14280 Bolu, Turkey
A R T I C L E I N F O
A B S T R A C T
Article history:
An efficient synthesis of 5-amino-7-aryl-3-oxo-8-(phenylsulfonyl)-thiazolo[3,2-a]pyri-
dine-6-carbonitriles was conducted utilizing multicomponent condensation reaction of
malononitrile, aromatic aldehydes and 2-phenylsulfonylmethylenethiazolidin-4-one in
one pot. Depending on the equivalence of the aldehyde, two different products were
obtained from moderate to excellent yields. Thirteen novel structures were characterized
by physical and spectroscopic methods (m.p., Rf, IR, NMR and mass analysis).
Received 10 August 2012
Accepted after revision 12 November 2012
Available online xxx
Keywords:
Knoevenagel reaction
Phenylsulfonyl
´
ß 2012 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Thiazolin-4-one
Heterocycles
Multicomponent reactions
1. Introduction
multicomponent reactions of 2-nitromethylenethiazoli-
dine with various active methylene, containing nitriles and
The chemistry of 2-alkylidenethiazolidin-4-one
compounds has been extensively studied over the years.
These compounds can be used for the synthesis of diverse
functionalized molecules, depending on the substituent of
the alkylidene part [1], and scaffolds prepared using these
compounds have shown to exhibit various biological
properties [2]. However, the synthetic applications of 2-
phenylsulfonylmethylenethiazolidin-4-one are rare in the
literature comparing to those of 2-alkylidenethiazolidin-4-
ones [3]. This has encouraged us to investigate this
substituent in multicomponent reactions, since phenyl-
sulfonyl substituent increases biological activity in some
heterocyclic compounds [4].
Multicomponent reactions (MCRs) play a significant
role to synthesize complex molecules [5] by reacting at
least three reagents in one pot. Mild reaction conditions
and easy purification steps attracted attention to these
kinds of reactions, and placed them into one of the green
chemistry routes [6]. Recently, we have reported the
a broad range of aldehydes [7]. In continuation of our
interest in heterocyclic enamine chemistry [8], we now
report multicomponent reactions of 2-phenylsulfonyl-
methylenethiazolidin-4-one with various aromatic alde-
hydes and malonitrile. We found that two different
products could be obtained depending on the equivalence
of the aldehyde.
2. Results and discussion
2-Phenylsulfonylmethylenethiazolidin-4-one was pre-
pared according to
a literature procedure [3a], and
identified by means of m.p., IR, 1H and 13C NMR. After
reviewing related alkylidenethiazolidin-4-ones and alky-
lidenepyrrolidine ester and nitrile geometries in previous
publications [9], we have decided to draw the double bond
geometry of the starting compound 1 Z isomer rather than E
isomer. Multicomponent reactions of 2-phenylsulfonyl-
methylene thiazolidin-4-one with malonitrile and aromatic
aldehydes were performed in anhydrous acetonitrile at
reflux temperature, and monitored by thin layer chroma-
tography (TLC). After 1 h, no 2-phenylsulfonylmethylene
thiazolidin-4-one remained on the TLC plate, which is
* Corresponding author.
E-mail address: altug_c@ibu.edu.tr (C. Altug˘).
1631-0748/$ – see front matter ß 2012 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
http://dx.doi.org/10.1016/j.crci.2012.11.002
Please cite this article in press as: Altug˘ C, Caner E. A facile strategy for the annulation of 2-phenylsulfonyl methylene
thiazolidin-4-one via multicomponent reactions. C. R. Chimie (2012), http://dx.doi.org/10.1016/j.crci.2012.11.002

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C. Altug˘, E. Caner / C. R. Chimie xxx (2012) xxx–xxx
Table 1
The reactions (Tables 1 and 2) proceed through the
Knoevenagel condensation of the aldehyde with malono-
nitrile, and then the addition of benzylidenemalononitrile
6 to enamine 1 followed by secondary amine attacks to one
of nitrile on benzylidenemalononitrile 6 ends with ring
cyclization. In our previous work, when 2-alkylidenethia-
zolin reacted with 2-phenylsulfonylacetonitrile and alde-
hyde, a mixture of enamine 4, and imine 8 tautomers was
obtained [7]. In the present work, we obtained compound 4
as a sole product (Scheme 1).
Reactions of 2-phenylsulfonylmethylenethiazolin-4-one with malononi-
trile and aldehydes.
Compound
R
Yield/%
When two equivalents of aldehyde were used, benzy-
lidene substituted 5-amino-7-aryl-3-oxo-8-(phenylsulfo-
nyl)-thiazolo[3,2-a]pyridine-6-carbonitriles were observed
in moderate to high yields as shown in Table 2. It was
also found that there was no direct effect of the stoichio-
metric amount of Et3N as a base to the MCR yield of
2-phenylsulfonylmethylene thiazolidin-4-one with malo-
nonitrile and aldehyde.
4a
4b
4c
4d
4e
4f
C6H5
73
84
74
86
68
71
4-NCC6H4
4-ClC6H4
2,6-DiClC6H3
2,4-DiClC6H3
4-O2NC6H4
In infrared spectra of compounds 4a–f and 5a–g, sulfone
groups showed two strong bands due to asymmetric
stretching at ca. 1307–1329 cmÀ1 and symmetric stretching
at ca. 1144–1154 cmÀ1. Bands at ca. 3312–3439 cmÀ1 are
ascribed to NH2 groups. Stretching vibrations of carbonyl
groups appeared at ca. 1658–1743 cmÀ1 and distinct cyano
indicative of the completion of reaction. The reactions
proceeded rapidly and afforded the corresponding thiazo-
lopyridin-4-ones 4a–f and benzylidene thiazolopyridin-4-
ones 5a–g in high yields. The results shown in Tables 1 and 2
clearly indicate the scope and generality of the reaction with
respect to aldehydes and malononitrile. The reactions
worked efficiently with a variety of aldehydes including
both electron-releasing and hetero-aromatic groups. Addi-
tionally, aforementioned reactions were also performed in
water as a solvent and without use of solvent via solid state
reaction. In both cases desired products were not obtained.
peaks were observed at ca. 2189–2201 cmÀ1. The 1H and 13
C
NMR spectra of compounds 4a–f and 5a–g were recorded in
d6-DMSO and gave good results, although the peak due to
adventitious water in the d6-DMSO obscured the one of
OCH3 resonance in compound 5f in one case, the resulting
proton, carbon NMR spectra as well as HRMS confirmed the
expected structure 5f. The signals due to the NH2 protons
Table 2
Reactions of 2-phenylsulfonylmethylenethiazolin-4-one 1 with malononitrile 2 and two equivalence of aldehydes 3.
Compound
R
Yield/%
5a
5b
5c
5d
5e
5f
4-ClC6H4
68
62
64
73
69
81
80
4-FC6H4
4-NCC6H4
3-BrC6H4
2,4-DiMeOC6H3
4-HO-3,5-DiMeOC6H2
3-Thienyl
5g
Scheme 1. Possible reaction mechanism for the formation of compounds 4.
Please cite this article in press as: Altug˘ C, Caner E. A facile strategy for the annulation of 2-phenylsulfonyl methylene
thiazolidin-4-one via multicomponent reactions. C. R. Chimie (2012), http://dx.doi.org/10.1016/j.crci.2012.11.002

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3
appeared at ca.
d
7.08–7.55 ppm, but in some cases
and malononitrile (1 mmol, 1.0 equiv, 66 mg) were mixed
in MeCN (10 mL) in a round-bottomed flask, and the
reaction mixture was stirred and heated. Triethylamine
(50 mg, 0.5 mmol) was added and the reaction mixture
was heated under reflux for 1 h (Tables 1 and 2). After
cooling, the solvent was removed under reduced pressure,
and the residue recrystallised from hexane/ethyl acetate
mixtures to give the pure products with data given below.
(compounds 4c, 5g, 5b) NH2 proton resonances overlapped
with aromatic protons and they were not easily detectable.
The chemical shifts of 4a–f CHAr protons showed remark-
able differences (
d 5.02–5.92 ppm) compared with CHAr
protons 5a–f ( 4.49–4.70 ppm) due to the substitution of
d
the benzylidene groups on the thiazoline fused to pyridine
ring. Carbonyl carbons of compounds 5a–g showed more
deshielded peaks than that of the compounds 4a–f due to
electron-withdrawing effects of the benzylidene group next
to carbonyl group in compounds 5a–g. In mass spectra of
compounds 5e and 5f, loss of M-Ar peaks 25 and 15% were
obtained, respectively.
4.4. 5-Amino-3-oxo-7-phenyl-8-(phenylsulfonyl)-3,7-
dihydro-2H-thiazolo[3,2-a]pyridine-6-carbonitrile (4a)
Obtained as yellow solid (300 mg, 73%), m.p. 229–
230 8C.
1647 (C = C), 1307 (SO2), 1153 (SO2). HRMS: requires for
20H15N3O3S2 [M+] 409.0555, found M+, 409.0558. dH
y
max, cmÀ1 (KBr) 3416 (NH2), 2189 (CN), 1701 (CO),
3. Conclusion
C
(400 MHz, DMSO-d6) 7.79–7.70 (m, 3H, aromatic CH of
SO2Ph), 7.61 (t, J = 7.7 Hz, 2H, aromatic CH of SO2Ph), 7.38
(t, J = 7.4 Hz, 2H, aromatic CH), 7.30 (t, J = 7.3 Hz, 2H,
aromatic CH), 7.20 (d, J = 7.0 Hz, 1H, aromatic CH), 7.16 (s,
2H, NH2), 5.16 (s, 2H, SCH2), 5.02 (s, 1H, CHPh). dC
(100 MHz; DMSO-d6) 160.7, 154.2, 152.2, 144.5, 138.1,
134.7, 129.7, 129.2, 128.5, 127.9, 127.4, 120.1, 112.8, 58.4,
55.9, 38.6.
In summary, we have achieved the synthesis of thirteen
novel phenylsulfonyl substitute thiazolopyridin-4-ones
via multicomponent reactions and identified these
compounds by means of spectroscopic methods.
4. Experimental
4.1. General
4.5. 5-amino-7-(4-cyanophenyl)-3-oxo-8-(phenylsulfonyl)-
3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbonitrile (4b)
Infrared spectra were recorded on a SHIMADZU FTIR-
8400S instrument (KBr disc). Mass spectra were recorded on
a Fisons VG Platform II spectrometer and on a Micromass
Q-TOF Micro spectrometer. NMR spectra were recorded on a
Bruker DPX 400 spectrometer operating at 400 MHz for 1H
and at 100 MHz for 13C at 25 8C. All chemical shifts are
reported in ppm downfieldfrom TMS. Couplingconstants (J)
are reported in Hz. Melting points were determined on a
MELTEMP apparatus and uncorrected. TLC was performed
using pre-coated plates with fluorescent indicator (Merck
5735). The stain solutions of permanganate and PMBA were
used for visualization of the TLC spots.
Obtained as brown solid (365 mg, 84%), mp. 197–
199 8C. y
max, cmÀ1 (KBr) 3331 (NH2), 2228 (CN of Ar), 2199
(CN), 1743 (CO), 1649 (C = C), 1327 (SO2), 1144 (SO2).
HRMS: Found M+ 435.0585 C21H15N4O3S2 [M+] requires
435.0586. dH (400 MHz, DMSO-d6) 7.87 (d, J = 8.2 Hz, 2H,
aromatic CH), 7.78–7.70 (m, 3H, aromatic CH of PhSO2),
7.61 (app. t, J = 7.9 Hz, 2H, aromatic CH), 7.41 (d, J = 8.2 Hz,
1H, aromatic CH), 7.30 (2H, br s, NH2), 5.18 (2H, app. s,
CH2S), 5.17 (1H, app. s, CHAr). dC (100 MHz; DMSO-d6)
160.9, 154.8, 152.4, 149.7, 138.0, 134.8, 133.2, 129.7, 128.6,
128.5, 122.2, 118.8, 111.4, 110.8, 58.9, 54.9, 38.5.
4.2. 2-Phenylsulfonylmethylenethiazolidin-4-one (1)
4.6. 5-Amino-7-(4-chlorophenyl)-3-oxo-8-(phenylsulfonyl)-
3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbonitrile (4c)
Phenylsulfonylacetonitrile (20 mmol, 3.624 g) and mer-
captoacetic acid (20 mmol, 1.842 g) were mixed in pyri-
dine (15 mL) in a round-bottomed flask and refluxed at
115 8C for overnight. After cooling, pyridine was removed
by evaporation, and the residue was applied for column
chromatography (EtOAc/Hexane: 1/3).
Obtained as pale yellow solid (330 mg, 74%), mp. 244–
246 8C. y
max, cmÀ1 (KBr) 3374 (NH2), 2201 (CN), 1720 (CO),
1647 (C = C), 1329 (SO2), 1146 (SO2). HRMS: Found M+,
443.0163. C20H14N3O3S235Cl [M+] requires 443.0165. dH
(400 MHz, DMSO-d6) 7.79–7.70 (3H, m, aromatic CH of
SO2Ph), 7.61 (2H, t, J = 7.8 Hz, aromatic CH of SO2Ph), 7.45
(2H, d, J = 8.4 Hz, aromatic CH), 7.25–7.19 (4H, m, aromatic
CH obscured with NH2), 5.17 (2H, s, CH2S), 5.06 (1H, s,
Obtained as yellow solid (3.2 g, 63%), m.p. 120–122 8C.
y
max, cmÀ1 (KBr) 3101 (NH2), 1735 (CO), 1589 (C = C), 1301
(SO2), 1138 (SO2). dH (400 MHz, DMSO-d6) 10.1 (br s, 1H,
NH), 7.89 (d, 2H, J = 7.1 Hz, aromatic CH), 7.64 (t, 1H,
J = 7.4 Hz, aromatic CH), 7.57 (t, 2H, J = 7.4, 7.1 Hz, aromatic
CH), 5.36 (s, 1H, CH = C), 3.80 (s, 2H, CH2S). dC (100 MHz;
DMSO-d6) 171.6, 152.2, 142.2, 133.3, 129.4, 126.6, 96.1,
77.3, 77.0, 76.8, 31.2.
CHAr). dC (100 MHz; DMSO-d6) 160.3, 154.1, 151.9, 143.0,
137.8, 134.3, 132.1, 129.3, 129.0, 128.8, 128.1, 119.6, 111.9,
58.1, 55.3, 37.6.
4.3. General reaction procedure for preparation of
thiazolo[3,2-a]pyridin-4-ones
4.7. 5-Amino-7-(2,6-dichlorophenyl)-3-oxo-8-
(phenylsulfonyl)-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-
carbonitrile (4d)
Aromatic aldehyde (1 mmol, 1.0 equiv for compounds
4a–f, 2 mmol, 2.0 equiv for compounds 5a–g), 2-phenyl-
sulfonylmethylenethiazolidine (1 mmol, 1 equiv, 255 mg)
Obtained as yellow solid (410 mg, 86%), mp. 277–
278 8C. y
max, cmÀ1 (KBr) 3422 (NH2), 2189 (CN), 1728 (CO),
Please cite this article in press as: Altug˘ C, Caner E. A facile strategy for the annulation of 2-phenylsulfonyl methylene
thiazolidin-4-one via multicomponent reactions. C. R. Chimie (2012), http://dx.doi.org/10.1016/j.crci.2012.11.002

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1647 (C = C), 1307 (SO2), 1154 (SO2). HRMS: Found M+,
476.9758. C20H13N3O3S235Cl2[M+] requires 476.9775. dH
(400 MHz, DMSO-d6) 7.75–7.69 (3H, m, aromatic CH of
SO2Ph), 7.60 (2H, d, J = 7.7 Hz, aromatic CH of SO2Ph), 7.57
(1H, dd, J = 8.0, 1.3 Hz, aromatic CH), 7.48 (1H, d, J = 6.9 Hz,
aromatic CH), 7.40 (1H, t, J = 8.0 Hz, aromatic CH), 7.29 (2H,
brs, NH2), 5.92 (1H, s, CHAr), 5.20 (2H, q, J = 14.5 Hz, CH2S).
dC (100 MHz; DMSO-d6) 161.6, 153.9, 153.6, 137.9, 135.7,
135.6, 134.7, 134.4, 131.5, 130.9, 129.6, 129.2, 128.6, 119.5,
108.7, 58.4, 52.4 and 35.3.
4.11. 5-Amino-2-(4-fluorobenzylidene)-7-(4-fluorophenyl)-
3-oxo-8-(phenyl sulfonyl)-3,7-dihydro-2H-thiazolo[3,2-
a]pyridine-6-carbonitrile (5b)
Obtained as pale yellow solid (425 mg, 80%), mp. 278–
279 8C. y
max, cmÀ1 (KBr) 3412 (NH2), 2203 (CN), 1707 (CO),
1649 (C = C), 1327 (SO2), 1144 (SO2). (Found: (M–H)+,
534.0751. C27H18N3O3S2F2 requires M, 534.0758). dH
(400 MHz, DMSO-d6) 7.95–7.72 (m, 3H, aromatic CH of
SO2Ph and CH = C), 7.72–7.58 (m, 3H, aromatic CH of SO2Ph),
7.58 – 7.51 (m, 4H, aromatic CH of ArF and NH2), 7.49–7.42
(m, 2H, aromatic CH of ArF), 7.35–7.16 (m, 2H, aromatic CH
4.8. 5-amino-7-(2,4-dichlorophenyl)-3-oxo-8-
(phenylsulfonyl)-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-
carbonitrile (4e)
of ArF), 7.01–6.80 (m, 2H), 4.57 (d, 1H). dC (100 MHz; DMSO-
d6) 166.2, 164.5, 163.0, 162.0, 160.6, 148.2, 142.1 140.9,
138.7, 134.2, 133.19, 130.6, 129.6, 127.3, 120.9, 119.1, 117.3,
115.6, 113.5, 66.2, 41.1. m/z (TOF ES+) 534 (M–H+, 100).
Obtained as yellow solid (325 mg, 68%), mp. 251–
252 8C. y
max, cmÀ1 (KBr) 3439 (NH2), 2189 (CN), 1722 (CO),
1657 (C = C), 1319 (SO2), 1152 (SO2). HRMS: Found M+,
476.9764. C20H13N3O3S235Cl2 [M+] requires 476.9775. dH
(400 MHz, DMSO-d6) 7.74–7.69 (3H, m, aromatic CH of
SO2Ph), 7.68 (1H, d, J = 2.0 Hz, aromatic CH), 7.59 (2H, t,
J = 7.8 Hz, aromatic CH of SO2Ph), 7.50 (1H, dd, J = 8.3,
2.0 Hz, aromatic CH), 7.37 (1H, s, aromatic CH), 7.34 (2H, br
s, NH2), 5.40 (1H, s, CHAr), 5.18 (2H, d, J = 2.6 Hz, CH2S). dC
(100 MHz; DMSO-d6) 161.5, 154.4, 152.7, 139.4, 138.1,
134.6, 133.6, 133.1, 131.8, 129.9, 129.7, 128.7, 128.5, 119.8,
110.5, 58.3, 53.5 and 36.3.
4.12. 5-Amino-2-(4-cyanobenzylidene)-7-(4-cyanophenyl)-
3-oxo-8-(phenyl sulfonyl)-3,7-dihydro-2H-thiazolo[3,2-
a]pyridine-6-carbonitrile (5c)
Obtained as yellow solid (339 mg, 62%), mp. 292–
294 8C. y
max, cmÀ1 (KBr) 3421 (NH2), 2245 (CN), 2230 (CN),
2195 (CN of pyridine), 1701 (CO), 1643 (C = C), 1327 (SO2),
1146 (SO2). (Found: (M–H)+, 548.0850. C29H18N5O3S2
requires M, 548.0851). dH (400 MHz, DMSO-d6) 8.08 (d,
J = 7.7 Hz, 2H, aromatic CH), 7.91 (d, J = 7.6 Hz, 2H, aromatic
CHof SO2Ph), 7.84 (s, 1H, CH = C), 7.68–7.62 (m, 3H,
aromatic CH of SO2Ph), 7.59 (d, J = 7.7 Hz, 2H, aromatic
CH), 7.55 (brs, 2H, NH2), 7.45 (app d, J = 5.5 Hz, 4H), 4.65 (s,
1H, CHAr). dC (100 MHz; DMSO-d6) 165.9, 148.4, 147.8,
142.5, 140.4, 138.1, 134.5, 133.7, 132.7, 131.1, 129.7, 129.6,
129.4, 127.4, 125.1, 119.1, 118.9, 118.8, 113.0, 112.4, 110.6,
65.2, 41.6. m/z (TOF ES+) 548 (M – H+, 100) and 405 (20).
4.9. 5-Amino-7-(4-nitrophenyl)-3-oxo-8-(phenylsulfonyl)-
3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbonitrile (4f)
Obtained as pale yellow solid (322 mg, 71%), mp. 255–
256 8C. y
max, cmÀ1 (KBr) 3312 (NH2), 2201 (CN), 1654 (CO),
1647 (C = C), 1327 (SO2), 1144 (SO2). HRMS: Found M+,
454.0406. C20H14N4O5S2 [M+] requires 454.0406. dH
(400 MHz, DMSO-d6) 8.26 (2H, d, J = 7.9 Hz, aromatic
CH), 7.77 – 7.70 (3H, m, aromatic CH of SO2Ph), 7.62
(2H, t, J = 7.5 Hz, aromatic CH of SO2Ph), 7.51 (2H, d,
J = 7.9 Hz, aromatic CH), 7.33 (2H, br s, NH2), 5.26 (1H, s,
CHAr), 5.19 (2H, s, CH2S). dC (100 MHz; DMSO-d6) 160.9,
154.9, 152.5, 151.6, 147.3, 138.1, 134.7, 129.7, 129.0, 128.5,
124.6, 119.9, 111.3, 58.4, 54.9, 38.3.
4.13. 5-Amino-2-(3-bromobenzylidene)-7-(3-
bromophenyl)-3-oxo-8-(phenyl sulfonyl)-3,7-dihydro-2H-
thiazolo[3,2-a]pyridine-6-carbonitrile (5d)
Obtained as yellow solid (480 mg, 73%), mp. 275–
276 8C. y
max, cmÀ1 (KBr) 3404 (NH2), 2201 (CN), 1697 (CO),
1653 (C = C), 1329 (SO2), 1147 (SO2). (Found: (M–H)+,
653.9155. C27H18N3O3S279Br2 requires M, 653.9156). dH
(400 MHz, DMSO-d6) 7.97 (s, 1H, aromatic CH), 7.77 (s, 1H,
CH = C), 7.73 (d, J = 7.8 Hz, 2H, aromatic CH), 7.67–7.56 (m,
4H, aromatic CH of SO2Ph and aromatic CH of ArBr), 7.53
(brs, 2H, NH2), 7.47–7.40 (m, 2H, aromatic CH of SO2Ph),
7.38 (s, 1H, aromatic CH), 7.30 (d, J = 7.7 Hz, 1H, aromatic
CH), 7.24 (d, 1H, J = 7.7 Hz, aromatic CH), 7.12 (t, J = 7.7 Hz,
4.10. 5-Amino-2-(4-chlorobenzylidene)-7-(4-chlorophenyl)-
3-oxo-8-(phenylsulfonyl)-3,7-dihydro-2H-thiazolo[3,2-
a]pyridine-6-carbonitrile (5a)
Obtained as yellow solid (384 mg, 68%), mp. 293–
294 8C.
y
max, cmÀ1 (KBr) 3373 (NH2), 2199 (CN), 1721
(CO), 1653 (C = C), 1325 (SO2), 1148 (SO2). (Found: (M–
H)+, 566.0176. C27H18N3O3S235Cl2 requires M, 566.0167).
dH (400 MHz, DMSO-d6) 7.79–7.75 (m, 3H, aromatic CH
of SO2Ph), 7.72 (d, J = 8.1 Hz, 2H, aromatic CH of SO2Ph),
7.65–7.56 (m, 3H, CH = C and aromatic CH), 7.52 (br s,
2H, NH2), 7.47–7.40 (m, 2H, aromatic CH), 7.28–7.21 (m,
2H, aromatic CH), 7.18–7.12 (m, 2H, aromatic CH), 4.54
(s, 1H, CHAr). dC (100 MHz; DMSO-d6) 166.1, 148.2,
142.1, 141.5, 140.7, 135.5, 134.2, 132.6, 132.5, 132.3,
130.5, 130.3, 130.1, 129.6, 128.6, 127.3, 122.1, 119.0,
113.3, 65.9, 41.2. m/z (TOF ES+) 566 (M–H + , 100) and
331 (15).
1H, aromatic CH), 4.57 (s, 1H, CHAr). dC (100 MHz; DMSO-
d6) 166.0, 148.2, 144.8, 142.3, 140.6, 136.2, 134.4, 133.8,
133.4, 132.1, 131.4, 130.9, 130.8, 129.8, 129.6, 128.5, 127.9,
127.2, 123.3, 123.1, 122.4, 119.1, 113.0, 65.8, 41.5. m/z (TOF
ES+) 655 (M – H+, 100) and 653 (52).
4.14. 5-Amino-2-(2,4-dimethoxybenzylidene)-7-(2,4-
dimethoxyphenyl)-3-oxo-8-(phenylsulfonyl)-3,7-dihydro-
2H-thiazolo[3,2-a]pyridine-6-carbonitrile (5e)
Obtained as yellow solid (395 mg, 64%), mp. 248–
249 8C. y
max, cmÀ1 (KBr) 3309 (NH2), 2187 (CN), 1707 (CO),
Please cite this article in press as: Altug˘ C, Caner E. A facile strategy for the annulation of 2-phenylsulfonyl methylene
thiazolidin-4-one via multicomponent reactions. C. R. Chimie (2012), http://dx.doi.org/10.1016/j.crci.2012.11.002

G Model
CRAS2C-3645; No. of Pages 5
C. Altug˘, E. Caner / C. R. Chimie xxx (2012) xxx–xxx
5
1643 (C = C), 1325 (SO2), 1144 (SO2). (Found: (M–H)+,
618.1362. C31H28N3O7S2 requires M, 618.1369). dH
(400 MHz, DMSO-d6) 7.93 (s, 1H, CH = C), 7.57–7.53 (m,
3H, aromatic CH of SO2Ph), 7.47 (app d, J = 7.6 Hz, 2H,
aromatic CH of SO2Ph), 7.37 (m, 1H, aromatic CH), 7.36 (br
s, 2H, NH2), 6.95 (d, J = 8.4 Hz, 1H), 6.84 (d, J = 8.4 Hz, 1H),
6.74 (d, J = 1.9 Hz, 1H), 6.32 (d, J = 7.2 Hz, 1H), 6.14 (s, 1H,
aromatic CH), 4.63 (s, 1H, CHAr), 3.95 (s, 3H, OCH3), 3.89 (s,
3H, OCH3), 3.70 (s, 3H, OCH3), 3.45 (s, 3H, OCH3). dC
(100 MHz; DMSO-d6) 166.3, 163.8, 160.6, 160.3, 158.3,
153.8, 148.9, 141.9, 141.0, 133.8, 131.2, 131.0, 129.3, 126.9,
126.8, 121.2, 119.4, 116.7, 115.1, 112.6, 107.2, 105.5, 99.2,
98.9, 64.9, 56.5, 56.2, 55.9, 55.7. m/z (TOF ES+) 618 (M–H+,
100), 480 (M–Ar+, 15) and 336 (35).
7.90 – 7.76 (m, 2H, aromatic CH of thienyl), 7.68–7.56 (m,
3H, aromatic CH of SO2Ph), 7.52 (s, 1H, CH = C), 7.50 – 7.36
(m, 4H, NH2 and aromatic CH of SO2Ph), 7.31 (s, 1H,
aromatic CH of thienyl), 7.19 (s, 1H, aromatic CH of
thienyl), 6.92–6.82 (m, 1H, aromatic CH of thienyl), 4.70 (s,
1H, CHAr). dC (100 MHz; DMSO-d6) 166.2, 148.5, 143.1,
141.6, 140.8, 135.8, 134.1, 131.9, 129.5, 129.1, 128.6, 127.8,
127.4, 126.9, 125.8, 123.4, 119.7, 119.3, 113.3, 65.7, 36.8.
m/z (TOF ES+) 510 (M–H+, 100), 336 (25) and 280 (45).
Acknowledgements
We are extremely grateful to the Abant Izzet Baysal
University, Directorate of Research Projects Commission
(BAP grant 2011.03.03.391).
4.15. 5-Amino-2-(4-hydroxy-3,5-dimethoxybenzylidene)-7-
(4-hydroxy-3,5-dimethoxy phenyl)-3-oxo-8-
(phenylsulfonyl)-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-
carbonitrile (5f)
Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/
j.crci.2012.11.002.
Obtained as yellow solid (450 mg, 69%), mp. 220
decomp. y
max, cmÀ1 (KBr) 3412 (NH2), 2203 (CN), 1701
(CO), 1649 (C = C), 1327 (SO2), 1144 (SO2). (Found: (M–H)+,
653.9155. C27H18N3O3S279Br2 requires M, 653.9156). dH
(400 MHz, DMSO-d6) 8.42 (s, 1H, OH), 8.24 (s, 1H, OH), 7.77
(app. d, J = 7.5 Hz, 2H, aromatic CH of SO2Ph), 7.64–7.57 (m,
2H, CH = C and aromatic CH of SO2Ph), 7.51–7.45 (m, 1H,
aromatic CH of SO2Ph), 7.37 (t, J = 7.1 Hz, 1H, aromatic CH
of SO2Ph), 7.08 (br s, 2H, NH2), 6.48 (s, 1H, aromatic CH),
6.29 (s, 1H, aromatic CH), 5.16 (s, 1H, aromatic CH), 4.93 (s,
1H, aromatic CH), 4.49 (s, 1H, CHAr), 3.88 (s, 3H, CH3O),
3.73 (s, 3H, CH3O), 3.59 (s, 2H, CH3O), 3.36 (s, 3H, obscured
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4.16. 5-Amino-3-oxo-8-(phenylsulfonyl)-7-(thiophen-3-yl)-
2-(thiophen-3-ylmethylene)-3,7-dihydro-2H-thiazolo[3,2-
a]pyridine-6-carbonitrile (5g)
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Biomol. Chem. 8 (2010) 4978;
Obtained as pale yellow solid (410 mg, 81%), mp. 265–
(b) C. Altug˘, Y. Du¨ru¨st, M.C. Elliott, B.M. Kariuki, Tetrahedron Lett. 50
(2009) 4919;
(c) C. Altug˘, Y. Du¨ru¨st, M.C. Elliott, Tetrahedron Lett. 50 (2009) 7392.
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266 8C. y
max, cmÀ1 (KBr) 3408 (NH2), 2205 (CN), 1701 (CO),
1647 (C = C), 1325 (SO2), 1144 (SO2). (Found: (M–H)+,
510.0062. C23H16N3O3S4 requires M, 510.0075). dH
(400 MHz, DMSO-d6) 8.16 (s, 1H, aromatic CH of thienyl),
Please cite this article in press as: Altug˘ C, Caner E. A facile strategy for the annulation of 2-phenylsulfonyl methylene
thiazolidin-4-one via multicomponent reactions. C. R. Chimie (2012), http://dx.doi.org/10.1016/j.crci.2012.11.002