Chemoselective annulation of 1,3-dithiin, -thiazine and -oxathiin rings on thiazoles using a green protocol

Article abstract of DOI:10.1016/j.tet.2006.06.030

Tandem Knoevenagel and Michael reactions of 3-arylrhodanines, aromatic aldehydes and ammonium N-aryldithiocarbamates diastereoselectively yield dithioesters, thiazol-5-ylmethyl N-aryldithiocarbamates, under solvent-free microwave irradiation conditions in

Full text of DOI:10.1016/j.tet.2006.06.030

Tetrahedron 62 (2006) 8029–8034
Chemoselective annulation of 1,3-dithiin, -thiazine and
-oxathiin rings on thiazoles using a green protocol
*
Lal Dhar S. Yadav and Vijai K. Rai
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad-211 002, India
Received 16 March 2006; revised 29 May 2006; accepted 8 June 2006
Available online 27 June 2006
Abstract—Tandem Knoevenagel and Michael reactions of 3-arylrhodanines, aromatic aldehydes and ammonium N-aryldithiocarbamates
diastereoselectively yield dithioesters, thiazol-5-ylmethyl N-aryldithiocarbamates, under solvent-free microwave irradiation conditions in
a one-pot procedure. Under the same conditions, the dithioesters are chemoselectively and expeditiously annulated with montmorillonite
K-10 clay, Li+-montmorillonite clay and I2 to give thiazolo-1,3-dithiins, -thiazines and -oxathiins, respectively.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
often involve expensive, toxic and hazardous solvents after
each step.
Recently, a number of oxathiin, thiazine and dithiin deriva-
tives have been reported to exhibit antiviral activity against
human immunodeficiency virus type 1 (HIV-1), poliovirus
type 1 (PV-1), coxsackie B virus type 3 (CoxB-3), vesicular
stomatitis virus (VSV) and herpes simplex virus type 1
(HSV-1).1 Moreover, dithiocarbamates have been exten-
sively investigated for their fungitoxicity and many of these,
viz., maneb, mancozeb, ziram, thiram and vapam, have
attained major recognition as agricultural fungicides.2,3
Compounds bearing the dithiocarbamate group, as part of
a heterocyclic structure have been relatively less studied
although some of these compounds, e.g., rhodanines and
mylone are known to display useful pesticidal properties.4,5
The thiazole nucleus is a well-known active core of various
bioactive molecules. Thus, heterocyclic systems resulting
from the annulation of oxathiin, thiazine and dithiin rings
on biologically versatile thiazole nuclei provide an attractive
scaffold that can be utilised for exploiting chemical diversity
and generating drug-like screening libraries to generate lead
candidates.
The application of microwave (MW) irradiation as a non-
conventional energy source for activation of reactions, in
general and under solvent-free conditions in particular, has
now gained popularity over the usual homogeneous and het-
erogeneous reactions. It provides chemical processes with
special attributes, such as enhanced reaction rates, higher
yields of pure products, better selectivity, improved ease of
manipulation, rapid optimisation of reactions in parallel
and several ecofriendly advantages in the context of green
chemistry.13–20 The application of MW irradiation has
recently been extended to modern drug discovery pro-
cesses,21,22 and has proved successful in the formation of
carbon–heteroatom and carbon–carbon bonds.23,24
Considering the above reports and the recently reported
results concerning MW accelerated Ugi three-component
coupling (3cc) reactions,25–27 in addition to continuing our
work on new solvent-free cyclisation procedures,28–32 we
devised a solvent-free MW-activated expeditious synthesis
of thiazolo-1,3-dithiins 5, -thiazines 6 and -oxathiins 7 via
one-pot Knoevenagel and Michael reactions (Scheme 1).
One-pot multi-component reactions (MCRs) have emerged
as an improved synthetic strategy for drug discovery pro-
cesses, 6–12 because multi-step synthesis produces consider-
able amounts of environmentally unfavourable wastes
predominantly due to complex isolation procedures that
2. Results and discussion
After some preliminary experimentation, it was found
that the envisaged synthesis (Scheme 1) was successful on
intermittent MW irradiation of an intimate mixture of 3-aryl-
rhodanines 1, aromatic aldehydes 2 and ammonium N-aryl-
dithiocarbamates 3 under solvent-free conditions for the
time specified in Table 1, followed by heterocyclisations
Keywords: Microwaves; Mineral supported; Solvent-free; Chemoselective
annulation; Thiazoles.
* Corresponding author. Tel.: +91 5322500652; fax: +91 5322545021;
e-mail: ldsyadav@hotmail.com
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.06.030

8030
L. D. S. Yadav, V. K. Rai / Tetrahedron 62 (2006) 8029–8034
Ar2
O
S
Ar1
S
O
C
MW
N
S
-
Ar2
+
+
S
+
H
H4NS
NHAr3
S
S
N
Ar3HN
S
O
Ar1
4
2
3
1
4
uncharged GS
+
Montmorillonite
K-10 clay
MW
S
-
MW Li Montmorillonite
I2
MW
H
clay
Ar2
Ar2
Ar2
H
+
S
+
δ
δ
H
H
S
S
S
S
S
+
δ
S
S
δ+
δ+
Ar3HN
O
I
S
Ar3N
S
N
N
Ar1
-
S
N
H
OH
O
Ar1
Ar1
H
Ar3
δ
δ
δ
-
-
I
dipolar TS
dipolar TS
dipolar TS
Ar2
S
Ar2
Ar2
S
S
S
S
S
S
S
S
Ar3N
N
O
Ar3N
N
S
N
N
S
Ar1
Ar1
Ar3
Ar1
7
6
5
HgO
EtOH
HgO
EtOH
Ar2
Ar2
S
S
S
O
S
O
O
N
N
Ar3N
N
Ar1
Ar1
S
Ar3
8
9
4- 7
Ar1
Ar2
Ar3
a
b
Ph
Ph
4-ClC6H4
4-MeOC6H4
Ph
4-ClC6H4
4-MeOC6H4
Ph
Ph
2-MeC6H4
c
d
2-MeC6H4
2-MeC6H4
2-MeC6H4
2-MeC6H4
2-MeC6H4
e
Scheme 1.
of the resulting dithioesters 4 with montmorillonite K-10
clay, Li+-montmorillonite, or I2 under the same condi-
tions. Isolation and purification by recrystallisation from
ethanol afforded the desired products 4–7 in 77–89%
yield (Table 1).
uncharged ground state (GS) in these reactions (Scheme 1).
The greater stabilisation of more polar TS by dipole–dipole
interactions with the electric field of microwaves as com-
pared to the less polar GS, may reduce the activation energy
(DGs), resulting in rate enhancement.17
For comparative purposes, the final temperature of the reac-
tion mixture was recorded immediately after the MW
irradiation for 2 min and was found to reach about 90 ꢀC.
Reactions were also carried out using a thermostated oil
bath at the same temperature (90 ꢀC) as the MW-activated
method, but for a longer (optimised) period of time (Table
1) to ascertain whether the MW method improved the yield
or simply increased the conversion rates. It was found that
significantly lower yields (42–52%) were obtained using
the oil baths rather compared to the MW-activated method
(Table 1). This observation may be rationalised by consider-
ing the formation of a dipolar transition state (TS) from an
Compounds 5–7 were synthesised from the same precursors
4 by intramolecular chemoselective heterocyclizations
(Scheme 1). The isomeric compounds 5 and 6 clearly differ
in their IR spectra; 5 exhibited a strong band attributed to
C]N (1635 cmꢁ1), whereas 6 was devoid of this band. Fur-
ther, the representative compounds 5a and 6a were con-
verted into their -6-one and -2,5-dione analogs 8a and 9a,
respectively, on treatment with HgO. This conversion,
involving desulfurisation of the exocyclic sulfur, provides
chemical evidence for the assigned structures of the isomeric
5a and 6a as the desulfurated products 8a and 9a are not
isomeric.

L. D. S. Yadav, V. K. Rai / Tetrahedron 62 (2006) 8029–8034
Table 1. Solvent-free microwave-activated synthesis of products 4–7
8031
Discover microwave system for 2 min. The reaction mixture
was then thoroughly mixed outside the MW oven for 2 min
and again irradiated for another 2 min. This intermittent irra-
diation-mixing cycle was repeated for the total irradiation
time of 4–6 min (Table 1). After completion of the reaction
as indicated by TLC (hexane/AcOEt, 8:2, v/v), water
(10 mL) was added to the reaction mixture and stirred
well. The yellowish precipitate thus obtained was washed
with water to give the crude product, which was recrystal-
lised from ethanol to afford a diastereomeric mixture
(>96:<4). The crude product ratios were >95:<5 as deter-
mined by 1H NMR spectroscopy. The product on second re-
crystallisation from ethanol furnished an analytically pure
sample of a single diastereomer 4 (Table 1). Comparison
of the J values to that reported in the literature,33–38 led to
the assignment of cis stereochemistry for 4, as the coupling
constant (JcyclicSCH, acyclicSCH¼5 Hz) of the major isomer
was lower than that for the minor trans diastereomer
(JcyclicSCH, acyclicSCH¼10 Hz).
Product
Time
MW (min)c Thermal (h)d MW Thermal
Yield (%)a
mp (ꢀC)b
4a
4b
4c
4d
4e
5a
5b
5c
5d
5e
6a
6b
6c
6d
6e
7a
7b
7c
7d
7e
6
6
4
4
6
2
3
2
2
3
3
3
5
4
4
5
4
3
3
4
5
5
4
5
3
88
79
82
87
80
89
80
83
85
80
88
81
82
85
78
87
83
80
85
77
51
43
42
46
43
52
47
48
50
42
45
43
42
48
45
51
48
43
48
43
118–120
127–128
133–135
138–139
130–131
139–140
143–144
148–150
150–152
145–146
154–156
159–160
153–154
164–166
162–163
158–159
167–168
175–176
152–153
170–171
12
10
10
12
12
10
10
12
12
10
10
10
8
8
10
4.2.1. Compound 4a. White needles (88%), mp 118–
120 ꢀC. IR (KBr) nmax 3147, 3025, 1700, 1602, 1580,
a
Yield of isolated and purified products.
b
1
1451, 1055 cmꢁ1. H NMR (DMSO-d6/TMS) d: 5.94 (d,
All compounds gave C, H and N analyses within ꢃ0.35% and satisfactory
spectral (IR, 1H NMR, 13C NMR and EIMS) data.
Microwave irradiation time (power ¼ 100 W).
1H, J¼5 Hz, acyclic SCH), 6.05 (d, 1H, J¼5 Hz, cyclic
SCH), 7.13–8.02 (m, 14Harom), 9.30 (br s, 1H, NH, ex-
changes with D2O). 13C NMR (DMSO-d6/TMS) d: 43.6,
79.0, 126.6, 127.2, 127.8, 129.5, 130.2, 130.9, 131.7,
132.5, 133.2, 133.8, 134.4, 135.1, 173.7, 192.9, 195.8.
Mass (m/z): 500, 502 (M, M+2). Anal. Calcd for
C23H17ClN2OS4: C, 55.13; H, 3.42; N, 5.59%. Found: C,
57.43; H, 3.34; N, 5.34%.
c
d
Time for oil-bath heating at 90 ꢀC.
3. Conclusion
In summary, we have developed a green protocol for an ex-
peditious synthesis of various potentially, pharmaceutically
and agrochemically useful thiazolo-1,3-dithiins, -thiazines
and -oxathiins starting from readily available simple sub-
strates employing solvent-free MW irradiation conditions.
4.2.2. Compound 4b. White needles (79%), mp 127–
128 ꢀC. IR (KBr) nmax 3143, 3022, 1705, 1601, 1575,
1
1445, 1050 cmꢁ1. H NMR (DMSO-d6/TMS) d: 3.70 (s,
3H, OMe), 5.91 (d, 1H, J¼5 Hz, acyclic SCH), 6.08 (d,
1H, J¼5 Hz, cyclic SCH), 7.03–7.99 (m, 14Harom), 9.28
(br s, 1H, NH, exchanges with D2O). 13C NMR (DMSO-
d6/TMS) d: 43.5, 55.3, 79.3, 125.9, 126.8, 127.5, 128.2,
129.0, 129.7, 130.3, 131.0, 131.6, 132.3, 133.0, 133.8,
173.5, 192.5, 195.7. Mass (m/z): 496 (M+). Anal. Calcd for
C24H20N2O2S4: C, 58.04; H, 4.06; N, 5.64%. Found: C,
58.37; H, 3.86; N, 5.46%.
4. Experimental
4.1. General
Melting points were determined by open glass capillary
method and are uncorrected. IR spectra in KBr were re-
corded on a Perkin–Elmer 993 IR spectrophotometer, H
1
NMR spectra were recorded on a Bruker WM-40 C
(400 MHz) FT spectrometer in DMSO-d6 using TMS as
internal reference. 13C NMR spectra were recorded on the
same instrument at 100 MHz using the same solvent and
internal reference. Mass spectra were recorded on a JEOL
D-300 mass spectrometer. Elemental analyses were carried
out in a Coleman automatic carbon, hydrogen and nitrogen
analyser. A CEM Discover Focused Microwave Synthesis
System operating at 2450 MHz was used at an output of
100 W for all the experiments. All chemicals used were
reagent grade and were used as received without further
purification. Silica gel-G was used for TLC.
4.2.3. Compound 4c. White needles (82%), mp 133–
135 ꢀC. IR (KBr) nmax 3140, 3020, 1707, 1600, 1580,
1
1450, 1057 cmꢁ1. H NMR (DMSO-d6/TMS) d: 2.29 (s,
6H, 2ꢂMe), 5.89 (d, 1H, J¼5 Hz, acyclic SCH), 6.11 (d,
1H, J¼5 Hz, cyclic SCH), 7.13–8.11 (m, 13Harom), 9.35
(br s, 1H, NH, exchanges with D2O). 13C NMR (DMSO-
d6/TMS) d: 20.3, 21.4, 43.1, 79.8, 125.3, 125.9, 126.6,
127.2, 128.8, 128.5, 129.1, 129.8, 130.4, 131.0, 131.8,
132.6, 133.3, 134.0, 134.7, 135.2, 173.4, 192.5, 195.4.
Mass (m/z): 494 (M+). Anal. Calcd for C25H22N2OS4: C,
60.70; H, 4.48; N, 5.66%. Found: C, 61.01; H, 4.29; N,
5.89%.
4.2. (3-Arylperhydro-4-oxo-2-thioxothiazol-5-yl)aryl-
methyl N-aryldithiocarbamates 4. General procedure
4.2.4. Compound 4d. White needles (87%), mp 138–
139 ꢀC. IR (KBr) nmax 3142, 3026, 1702, 1605, 1587,
An intimate mixture of a 3-arylrhodanine 1 (2.0 mmol), an
aromatic aldehyde 2 (2.0 mmol) and an ammonium N-aryl-
dithiocarbamate 3 (2.0 mmol) were taken in a 20 mL vial
and subjected to MW irradiation at 100 W in a CEM
1455, 1058 cmꢁ1 1H NMR (DMSO-d6/TMS) d: 2.32
.
(s, 6H, 2ꢂMe), 5.90 (d, 1H, J¼5 Hz, acyclic SCH), 6.07
(d, 1H, J¼5 Hz, cyclic SCH), 7.03–8.12 (m, 12Harom),
9.30 (br s, 1H, NH, exchanges with D2O). 13C NMR

8032
L. D. S. Yadav, V. K. Rai / Tetrahedron 62 (2006) 8029–8034
(DMSO-d6/TMS) d: 20.5, 21.6, 43.7, 80.0, 125.5, 126.1,
126.7, 127.4, 128.0, 128.6, 129.3, 130.0, 130.6, 131.3,
131.9, 132.5, 133.1, 133.8, 134.5, 135.2, 173.3, 192.8,
195.7. Mass (m/z): 528, 530 (M, M+2). Anal. Calcd for
C25H21ClN2OS4: C, 56.74; H, 4.00; N, 5.29%. Found: C,
56.99; H, 3.89; N, 5.48%.
4.3.4. Compound 5d. Yellowish needles (85%), mp 150–
152 ꢀC. IR (KBr) nmax 3024, 1633, 1605, 1581, 1451,
1059 cmꢁ1 1H NMR (DMSO-d6/TMS) d: 2.33 (s, 6H,
.
2ꢂMe), 4.48 (s, 1H, Ar-CH), 7.10–7.91 (m, 12Harom). 13C
NMR (DMSO-d6/TMS) d: 20.2, 21.7, 42.4, 81.4, 125.3,
126.0, 126.7, 127.4, 128.1, 128.7, 129.3, 130.0, 130.8,
131.4, 132.0, 132.7, 133.4, 134.1, 134.7, 135.3, 157.9,
160.0, 192.8. Mass (m/z): 510, 512 (M, M+2). Anal. Calcd
for C25H19ClN2S4: C, 58.74; H, 3.75; N, 5.48%. Found: C,
57.79; H, 3.58; N, 5.67%.
4.2.5. Compound 4e. White needles (80%), mp 130–
131 ꢀC. IR (KBr) nmax 3147, 3028, 1706, 1608, 1579,
1
1449, 1051 cmꢁ1. H NMR (DMSO-d6/TMS) d: 2.37 (s,
6H, 2ꢂMe), 3.68 (s, 3H, OMe), 5.85 (d, 1H, J¼5 Hz, acyclic
SCH), 6.01 (d, 1H, J¼5 Hz, cyclic SCH), 7.01–8.11 (m,
12Harom), 9.28 (br s, 1H, NH, exchanges with D2O). 13C
NMR (DMSO-d6/TMS) d: 20.4, 21.5, 43.5, 55.1, 79.6,
125.4, 126.1, 126.7, 127.4, 127.9, 128.5, 129.2, 129.9,
130.5, 131.8, 132.4, 133.1, 133.7, 134.4, 135.1, 135.8,
173.2, 192.7, 195.5. Mass (m/z): 524 (M+). Anal. Calcd for
C26H24N2O2S4: C, 59.51; H, 4.61; N, 5.34%. Found: C,
59.79; H, 4.48; N, 5.54%.
4.3.5. Compound 5e. Yellowish needles (80%), mp 145–
146 ꢀC. IR (KBr) nmax 3021, 1631, 1601, 1580, 1448,
1061 cmꢁ1 1H NMR (DMSO-d6/TMS) d: 2.31 (s, 6H,
.
2ꢂMe), 3.70 (s, 3H, OMe), 4.42 (s, 1H, Ar-CH), 7.09–
7.95 (m, 12Harom). 13C NMR (DMSO-d6/TMS) d: 20.3,
21.6, 42.3, 54.8, 80.8, 125.5, 126.1, 126.7, 127.3, 128.0,
128.7, 129.4, 130.0, 130.6, 131.2, 131.9, 132.5, 133.2,
133.8, 134.4, 135.1, 158.8, 159.9, 192.6. Mass (m/z): 506
(M+). Anal. Calcd for C26H22N2OS4: C, 61.63; H, 4.38; N,
5.53%. Found: C, 61.90; H, 4.23; N, 5.31%.
4.3. 3,7-Diaryl-5-(arylamino)-2,3,5,7-tetrahydrothia-
zolo[4,5-d][1,3]dithiin-2-thiones 5. General procedure
4.4. 3,4,7-Triaryl-2,3,4,5,7-pentahydrothiazolo[4,5-d]-
[1,3]thiazine-2,5-dithiones 6. General procedure
Thoroughly mixed dithioesters 4 (2.0 mmol) and montmo-
rillonite K-10 clay (0.2 g) were taken in a 20 mL vial and
subjected to intermittent MW irradiation at 100 W at the in-
tervals of 2 min for the total irradiation time of 10–12 min
(Table 1). After completion of the reaction as indicated by
TLC (hexane/AcOEt, 8:2, v/v), water (10 mL) was added
to the reaction mixture and stirred well. The yellowish
precipitate thus obtained was washed with water to give
the crude product, which was recrystallised from ethanol
to afford analytically pure sample of 5.
An intimate mixture of dithioesters 4 (2.0 mmol) and Li+-
montmorillonite clay (0.2 g) was taken in a 20 mL vial and
intermittently irradiated at the intervals of 2 min in a CEM
Discover MW system at 100 W for the total irradiation
time of 10–12 min (Table 1). To obtain analytically pure
sample of compounds 6, the same procedure was adopted
as described for 5.
4.4.1. Compound 6a. Yellowish needles (88%), mp 154–
156 ꢀC. IR (KBr) nmax 3027, 1605, 1585, 1445,
4.3.1. Compound 5a. Yellowish needles (89%), mp 139–
140 ꢀC. IR (KBr) nmax 3025, 1635, 1604, 1585, 1456,
1
1057 cmꢁ1. H NMR (DMSO-d6/TMS) d: 4.39 (s, 1H, Ar-
1060 cmꢁ1. H NMR (DMSO-d6/TMS) d: 4.45 (s, 1H, Ar-
CH), 7.02–7.91 (m, 14Harom). 13C NMR (DMSO-d6/TMS)
d: 42.1, 78.9, 125.8, 126.6, 127.3, 128.0, 128.8, 129.7,
130.4, 131.1, 131.9, 132.8, 133.6, 134.9, 151.9, 191.5,
192.3. Mass (m/z): 482, 484 (M, M+2). Anal. Calcd for
C23H15ClN2S4: C, 57.18; H, 3.13; N, 5.80%. Found: C,
56.83; H, 3.25; N, 5.56%.
1
CH), 7.13–7.95 (m, 14Harom). 13C NMR (DMSO-d6/TMS)
d: 42.5, 80.5, 126.7, 127.4, 128.0, 128.6, 129.3, 130.1,
130.7, 131.5, 132.3, 133.0, 133.6, 134.3, 158.5, 159.8,
192.5. Mass (m/z): 482, 484 (M, M+2). Anal. Calcd for
C23H15ClN2S4: C, 57.18; H, 3.13; N, 5.80%. Found: C,
57.47; H, 3.34; N, 5.49%.
4.4.2. Compound 6b. Yellowish needles (81%), mp 159–
160 ꢀC. IR (KBr) nmax 3021, 1598, 1583, 1451,
4.3.2. Compound 5b. Yellowish needles (80%), mp 143–
144 ꢀC. IR (KBr) nmax 3021, 1631, 1603, 1584, 1455,
1051 cmꢁ1 1H NMR (DMSO-d6/TMS) d: 3.75 (s, 3H,
.
1058 cmꢁ1
.
1H NMR (DMSO-d6/TMS) d: 3.73 (s, 3H,
OMe), 4.43 (s, 1H, Ar-CH), 7.13–7.95 (m, 14Harom). 13C
NMR (DMSO-d6/TMS) d: 42.0, 54.7, 80.2, 125.7, 126.5,
127.3, 128.0, 128.8, 129.7, 130.4, 131.1, 131.9, 132.8,
133.6, 134.9, 151.9, 191.5, 192.3. Mass (m/z): 478 (M+).
Anal. Calcd for C24H18N2OS4: C, 60.22; H, 3.79; N,
5.85%. Found: C, 60.57; H, 3.64; N, 5.61%.
OMe), 4.41 (s, 1H, Ar-CH), 7.11–7.93 (m, 14Harom). 13C
NMR (DMSO-d6/TMS) d: 42.4, 54.9, 81.3, 126.6, 127.3,
128.1, 128.7, 129.4, 130.1, 130.8, 131.6, 132.2, 132.9,
133.5, 134.2, 158.4, 159.6, 192.3. Mass (m/z): 478 (M+).
Anal. Calcd for C24H18N2OS4: C, 60.22; H, 3.79; N,
5.85%. Found: C, 59.87; H, 3.88; N, 5.65%.
4.4.3. Compound 6c. Yellowish needles (82%), mp 153–
154 ꢀC. IR (KBr) nmax 3022, 1601, 1579, 1450,
4.3.3. Compound 5c. Yellowish needles (83%), mp 148–
150 ꢀC. IR (KBr) nmax 3020, 1630, 1598, 1579, 1449,
1053 cmꢁ1 1H NMR (DMSO-d6/TMS) d: 2.32 (s, 6H,
.
1056 cmꢁ1
.
1H NMR (DMSO-d6/TMS) d: 2.30 (s, 6H,
2ꢂMe), 4.37 (s, 1H, Ar-CH), 7.05–7.98 (m, 13Harom). 13C
NMR (DMSO-d6/TMS) d: 20.1, 21.3, 41.5, 78.8, 125.4,
126.0, 126.7, 127.3, 127.9, 128.6, 129.4, 130.0, 130.6,
131.2, 131.9, 132.5, 133.1, 133.8, 134.6, 135.0, 151.8,
191.5, 192.2. Mass (m/z): 476 (M+). Anal. Calcd for
C25H20N2S4: C, 62.99; H, 4.23; N, 5.88%. Found: C,
62.69; H, 4.11; N, 5.68%.
2ꢂMe), 4.43 (s, 1H, Ar-CH), 7.15–7.89 (m, 13Harom). 13C
NMR (DMSO-d6/TMS) d: 20.3, 21.5, 42.2, 79.9, 125.4,
126.0, 126.6, 127.3, 128.0, 128.6, 129.4, 130.0, 130.7, 131.3,
131.9, 132.7, 133.3, 134.0, 134.6, 135.2, 158.1, 159.8, 192.5.
Mass (m/z): 476 (M+). Anal. Calcd for C25H20N2S4: C,
62.99; H, 4.23; N, 5.88%. Found: C, 62.72; H, 4.09; N, 5.98%.

L. D. S. Yadav, V. K. Rai / Tetrahedron 62 (2006) 8029–8034
8033
4.4.4. Compound 6d. Yellowish needles (85%), mp 164–
166 ꢀC. IR (KBr) nmax 3026, 1604, 1584, 1448,
4.5.4. Compound 7d. Yellowish needles (85%), mp 152–
153 ꢀC. IR (KBr) nmax 3026, 1633, 1599, 1585, 1445,
1059 cmꢁ1
.
1H NMR (DMSO-d6/TMS) d: 2.31 (s, 6H,
1054 cmꢁ1 1H NMR (DMSO-d6/TMS) d: 2.36 (s, 6H,
.
2ꢂMe), 4.42 (s, 1H, Ar-CH), 7.09–7.85 (m, 12Harom). 13C
NMR (DMSO-d6/TMS) d: 20.6, 21.5, 41.9, 81.0, 125.3,
125.9, 126.5, 127.2, 127.8, 128.5, 129.1, 129.8, 130.5,
131.1, 131.8, 132.4, 133.0, 133.7, 134.3, 135.0, 151.6,
191.7, 192.4. Mass (m/z): 510, 512 (M, M+2). Anal. Calcd
for C25H19ClN2S4: C, 58.74; H, 3.75; N, 5.48%. Found: C,
58.36; H, 3.85; N, 5.73%.
2ꢂMe), 4.52 (s, 1H, Ar-CH), 7.19–7.81 (m, 12Harom). 13C
NMR (DMSO-d6/TMS) d: 20.5, 21.7, 42.9, 81.3, 125.4,
126.0, 126.7, 127.3, 127.9, 128.5, 129.2, 129.8, 130.5,
131.1, 131.7, 132.3, 133.0, 133.6, 134.3, 134.9, 169.8,
162.7, 191.5. Mass (m/z): 494, 496 (M, M+2). Anal. Calcd
for C25H19ClN2OS3: C, 60.65; H, 3.87; N, 5.66%. Found:
C, 60.34; H, 3.72; N, 5.87%.
4.4.5. Compound 6e. Yellowish needles (78%), mp 162–
163 ꢀC. IR (KBr) nmax 3020, 1602, 1580, 1446,
4.5.5. Compound 7e. Yellowish needles (77%), mp 170–
171 ꢀC. IR (KBr) nmax 3023, 1636, 1600, 1580, 1451,
1052 cmꢁ1
.
1H NMR (DMSO-d6/TMS) d: 2.28 (s, 6H,
1056 cmꢁ1 1H NMR (DMSO-d6/TMS) d: 2.29 (s, 6H,
.
2ꢂMe), 3.72 (s, 3H, OMe), 4.36 (s, 1H, Ar-CH), 7.11–
7.88 (m, 12Harom). 13C NMR (DMSO-d6/TMS) d: 20.4,
21.4, 41.7, 54.6, 81.1, 125.4, 126.1, 126.7, 127.3,
127.9, 128.6, 129.3, 130.0, 130.6, 131.3, 132.0, 132.6,
132.8, 133.6, 134.3, 135.0, 151.7, 191.6, 192.3. Mass
(m/z): 506 (M+). Anal. Calcd for C26H22N2OS4: C,
61.63; H, 4.38; N, 5.53%. Found: C, 61.30; H, 4.51;
N, 5.73%.
2ꢂMe), 3.82 (s, 3H, OMe), 4.48 (s, 1H, Ar-CH), 6.99–
7.85 (m, 12Harom). 13C NMR (DMSO-d6/TMS) d: 20.2,
21.5, 42.7, 54.8, 79.9, 125.2, 125.8, 126.4, 127.1, 127.7,
128.3, 129.0, 129.6, 130.3, 130.9, 131.6, 132.2, 133.5,
133.8, 134.1, 134.8, 161.5, 162.6, 191.7. Mass (m/z): 490
(M+). Anal. Calcd for C26H22N2O2S3: C, 63.64; H, 4.52;
N, 5.71%. Found: C, 61.90; H, 4.40; N, 5.46%.
4.6. Conversion of 5a and 6a into their 2-one and
2,5-dione analogs 8a and 9a, respectively
4.5. 3,7-Diaryl-5-(arylamino)-2,3,5,7-tetrahydrothia-
zolo[4,5-e][1,3]oxathiin-2-thiones 7. General procedure
Compounds 5a (2.0 mmol) and HgO (4.0 mmol) were re-
fluxed in ethanol (25 mL) for 13 h.39 The precipitated HgS
was filtered off, and the filtrate was concentrated and cooled
to furnish 8a, which was recrystallised from ethanol as white
needles. Compound 9a was similarly prepared from 6a and
recrystallised from ethanol.
Thoroughly mixed dithioesters 4 (2 mmol) and I2 (0.56 g)
were taken in a 20 mL vial and subjected to intermittent
MW irradiation at 100 W at the intervals of 2 min for the
total irradiation time of 8–10 min (Table 1). To obtain ana-
lytically pure sample of compounds 7, the same procedure
was adopted as described for 5.
4.6.1. Compound 8a. Yellowish needles, mp 138 ꢀC. IR
1
4.5.1. Compound 7a. Yellowish needles (87%), mp 158–
159 ꢀC. IR (KBr) nmax 3025, 1639, 1605, 1586, 1455,
(KBr) nmax 3024, 1705, 1638, 1604, 1585, 1451 cmꢁ1. H
NMR (DMSO-d6/TMS) d: 4.49 (s, 1H, Ar-CH), 7.03–7.95
(m, 14Harom). 13C NMR (DMSO-d6/TMS) d: 41.9, 80.9,
126.2, 126.8, 127.6, 128.5, 129.3, 130.0, 130.6, 131.3,
132.1, 132.7, 133.6, 134.5, 158.4, 160.0, 164.9. Mass
(m/z): 466, 468 (M, M+2). Anal. Calcd for C23H15ClN2OS3:
C, 59.15; H, 3.24; N, 6.00%. Found: C, 59.50; H, 3.13; N,
5.79%.
1
1058 cmꢁ1. H NMR (DMSO-d6/TMS) d: 4.39 (s, 1H, Ar-
CH), 7.03–7.85 (m, 14Harom). 13C NMR (DMSO-d6/TMS)
d: 42.7, 79.5, 125.9, 126.6, 127.4, 128.2, 128.9, 129.7,
130.5, 131.4, 132.1, 132.9, 133.7, 134.6, 161.2, 162.9,
191.8. Mass (m/z): 466, 468 (M, M+2). Anal. Calcd for
C23H15ClN2OS3: C, 59.15; H, 3.24; N, 6.00%. Found: C,
60.10; H, 3.39; N, 5.78%.
4.6.2. Compound 9a. Yellowish needles, mp 182–183 ꢀC.
4.5.2. Compound 7b. Yellowish needles (83%), mp 167–
168 ꢀC. IR (KBr) nmax 3022, 1635, 1601, 1578, 1448,
IR (KBr) nmax 3022, 1707, 1676, 1605, 1580, 1448 cmꢁ1
.
1H NMR (DMSO-d6/TMS) d: 4.50 (s, 1H, Ar-CH), 7.12–
7.98 (m, 14Harom). 13C NMR (DMSO-d6/TMS) d: 43.7,
80.5, 126.3, 126.9, 127.7, 128.5, 129.4, 130.2, 130.9,
131.6, 132.5, 133.5, 133.9, 134.9, 152.1, 165.3, 166.2.
Mass (m/z): 450, 452 (M, M+2). Anal. Calcd for
C23H15ClN2O2S2: C, 61.26; H, 3.35; N, 6.21%. Found: C,
6098; H, 3.49; N, 5.99%.
1056 cmꢁ1 1H NMR (DMSO-d6/TMS) d: 3.79 (s, 3H,
.
OMe), 4.51 (s, 1H, Ar-CH), 7.32–7.95 (m, 14Harom). 13C
NMR (DMSO-d6/TMS) d: 42.5, 55.2, 81.2, 125.8, 126.5,
127.5, 128.3, 129.2, 130.1, 130.9, 131.7, 132.5, 133.2,
133.9, 134.7, 161.0, 162.7, 191.7. Mass (m/z): 462 (M+).
Anal. Calcd for C24H18N2O2S3: C, 62.31; H, 3.92; N,
6.06%. Found: C, 62.66; H, 3.79; N, 6.26%.
4.5.3. Compound 7c. Yellowish needles (80%), mp 175–
176 ꢀC. IR (KBr) nmax 3020, 1635, 1603, 1581, 1449,
Acknowledgements
1053 cmꢁ1
.
1H NMR (DMSO-d6/TMS) d: 2.27 (s, 6H,
We sincerely thank SAIF, CDRI, Lucknow, for providing
microanalyses and spectra.
2ꢂMe), 4.44 (s, 1H, Ar-CH), 7.05–7.99 (m, 13Harom). 13C
NMR (DMSO-d6/TMS) d: 20.3, 21.4, 42.2, 80.0, 125.3,
125.9, 126.6, 127.3, 128.0, 128.7, 129.4, 130.0, 130.6,
131.2, 131.9, 132.5, 133.2, 133.8, 134.4, 135.2, 160.9,
162.5, 191.3. Mass (m/z): 460 (M+). Anal. Calcd for
C25H20N2OS3: C, 65.19; H, 4.38; N, 6.08%. Found: C,
65.38; H, 4.22; N, 5.90%.
References and notes
1. Hahn, H. G.; Rhee, H. K.; Lee, C. K.; Whang, K. J. Arch.
Pharm. Res. 2000, 4, 315–323.

8034
L. D. S. Yadav, V. K. Rai / Tetrahedron 62 (2006) 8029–8034
2. Spencer, E. Y. Bull. Conn. Agric. Exp. Stn. (New Haven) 1963,
95–112.
3. Thorn, G. D.; Ludwig, R. A. The Dithiocarbamates and
Related Compounds; Elsevier: Amsterdam, 1962; pp 169–
185, 224–271.
22. Alexandre, F. R.; Domon, L.; Frere, S.; Testard, A.; Thiery, V.;
Besson, T. Mol. Divers. 2003, 7, 273–280.
23. Varma, R. S. J. Heterocycl. Chem. 1999, 36, 1565–1571.
24. Larhed, M.; Moberg, C.; Hallberg, A. Acc. Chem. Res. 2002,
35, 717–727.
4. Brown, F. C. Chem. Rev. 1961, 61, 463–521.
5. Singh, H.; Mishra, A. R.; Yadav, L. D. S. Indian J. Chem. 1987,
26B, 1200–1202.
6. Ugi, I.; Domling, A. Endeavour 1994, 18, 115–122.
7. Heck, S.; Domling, A. Synlett 2000, 424–426.
8. Kraus, G. A.; Nagy, J. O. Tetrahedron 1985, 41, 3537–
3545.
9. Posner, G. H. Chem. Rev. 1986, 86, 831–834.
10. Uji, I. J. Prakt. Chem. 1997, 339, 499–516.
11. Bienayme’, H.; Bouzid, K. Tetrahedron Lett. 1988, 39, 2735–
2738.
25. Varma, R. S.; Kumar, D. Tetrahedron Lett. 1999, 40, 7665–
7669.
26. Lidstrom, P.; Westman, J.; Lewis, A. Comb. Chem. High
Throughput Screen. 2002, 5, 441–458.
27. Ireland, S. M.; Tye, H.; Whittaker, M. Tetrahedron Lett. 2003,
44, 4369–4371.
28. Yadav, L. D. S.; Rai, V. K. Tetrahedron Lett. 2006, 47,
395–397.
29. Yadav, L. D. S.; Kapoor, R. Synlett 2005, 3055–3058.
30. Yadav, L. D. S.; Yadav, S.; Rai, V. K. Tetrahedron 2005, 61,
10013–10017.
12. Ziegler, T.; Kaiser, H.-J.; Scholomer, R.; Koch, C. Tetrahedron
1999, 55, 8397–8408.
31. Yadav, L. D. S.; Kapoor, R. J. Org. Chem. 2004, 69, 8118–
8120.
13. Caddick, S. Tetrahedron 1995, 51, 10403–10432.
14. Loupy, A.; Petit, A.; Hamelin, J.; Texier-Bouller, F.; Jacquault,
P.; Mathe, D. Synthesis 1998, 1213–1234.
15. Varma, R. S. Green Chem. 1999, 1, 43–45.
16. Lidstrom, P.; Tierney, J.; Wathey, B.; Westman, J. Tetrahedron
2001, 57, 9225–9283.
17. Perreux, L.; Loupy, A. Tetrahedron 2001, 57, 9199–9223.
18. Balogh, M.; Laszlo, P. Organic Chemistry Using Clays;
Springer: Berlin, 1993.
32. Yadav, L. D. S.; Yadav, B. S.; Rai, V. K. Tetrahedron Lett. 2004,
45, 5351–5353.
33. Evans, D. A.; Nelson, J. V.; Vogel, E.; Taber, T. R. J. Am. Chem.
Soc. 1981, 103, 3099–3111.
34. Mukaiyama, T.; Iwasawa, N. Chem. Lett. 1984, 753–756.
35. Evans, D. A.; Taber, T. R. Tetrahedron Lett. 1980, 21, 4675–
4678.
36. Hirayama, M.; Gamoh, K.; Ikekawa, N. Chem. Lett. 1982,
491–494.
19. Chisem, J.; Chisem, I. C.; Rafelt, J. S.; Macquarrie, D. J.; Clark,
J. H. Chem. Commun. 1997, 2203–2204.
37. Tanikaga, R.; Hamamura, K.; Kaji, A. Chem. Lett. 1988,
977–980.
20. Meshram, H. M.; Shekhar, K. C.; Ganesh, Y. S. S.; Yadav, J. S.
Synlett 2000, 1273–1275.
38. Yadav, L. D. S.; Dubey, S.; Yadav, B. S. Tetrahedron 2003, 59,
5411–5415.
21. Strohmeier, G. A.; Kappe, C. O. J. Comb. Chem. 2002, 4,
154–161.
39. Silberg, Al.; Cosma, N. Acad. Repub. Pop. Rom., Fil. Cluj. Stud.
Cercet. Chim. 1959, 10, 151–162;Chem. Abstr. 1960, 54, 8795e.