Thiourea to bicyclic scaffolds: highly regio- and stereoselective routes to dithiazolopyrimidines

Article abstract of DOI:10.1016/j.tet.2007.04.033

Microwave-activated solvent-free Michael addition of 3-imino-1,4,2-dithiazoles to 4-arylidene-5(4H)-oxazolones furnished isolable adducts regio- and diastereoselectively, which underwent ring transformation to yield the target dithiazolopyrimidines. Alter

Full text of DOI:10.1016/j.tet.2007.04.033

Tetrahedron 63 (2007) 6924–6931
Thiourea to bicyclic scaffolds: highly regio- and stereoselective
routes to dithiazolopyrimidines
*
Lal Dhar S. Yadav and Vijai K. Rai
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211 002, Uttar Pradesh, India
Received 4 October 2006; revised 27 March 2007; accepted 12 April 2007
Available online 19 April 2007
Abstract—Microwave-activated solvent-free Michael addition of 3-imino-1,4,2-dithiazoles to 4-arylidene-5(4H)-oxazolones furnished
isolable adducts regio- and diastereoselectively, which underwent ring transformation to yield the target dithiazolopyrimidines. Alternatively,
the similar conjugate addition of methanesulfinylmethylisothioureas to 4-arylidene-5(4H)-oxazolones diastereoselectively afforded Michael
adducts, which underwent ring transformation followed by heterocyclization via deoxygenative demethylation with thionyl chloride to yield
the same products dithiazolopyrimidines regio- and diastereoselectively.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
processes with special attributes such as enhanced reaction
rates, higher yields of pure products, better selectivity, im-
proved ease of manipulation, rapid optimization of reactions
in parallel, and several ecofriendly advantages in the context
of green chemistry.12–19 The application of MW irradiation
to provide enhanced reaction rates and improved product
yields in chemical synthesis has been extended to modern
drug discovery processes,20,21 and is proving quite suc-
cessful in the formation of carbon–carbon and carbon–
heteroatom bonds.22,23
In general, heterocycles encompassing a pyrimidine unit
have found applications in a wide spectrum of biological
and therapeutic areas.1–3 Cancer and AIDS have long been
recognized as the most common cause of death. Accord-
ingly, many diverse strategies have been employed to
develop new drugs or to improve existing treatments. A lit-
erature survey described a variety of substituted thiazoles
and antimetabolite thiazolopyrimidine derivatives that re-
ceived a great deal of attention for their anticancer,4,5 antivi-
ral,6,7 antiinflammatory and antimicrobial8 activities. Highly
substituted heterocycles are interesting as potentially biode-
gradable pharmaceuticals and agrochemicals.9–11
Considering the above valid points and our continued inter-
est in devising new solvent-free cyclization methods,24–28
we report herein the MW assisted highly diastereoselective
formation of pyrimidines 8 and 6 under catalyst and sol-
vent-free conditions. The cornerstone in our approach is
the conversion of thiourea into isothioureas 2 bearing a sul-
finyl (pS]O) function for effecting the desired hetero-
cyclizations via deoxygenative demethylation using thionyl
chloride. Interestingly, the present stereoselective synthetic
protocols yielding dithiazolopyrimidines 6 starting from
thiourea 1 are hitherto unreported to the best of our knowl-
edge, and are among the few examples showing increased
stereoselectivity under MW irradiation compared to conven-
tional heating.
Thus, we envisaged the synthesis of a new highly substituted
dithiazolopyrimidine system, incorporating the biologically
versatile pyrimidine nucleus fused with a dithiazole ring, as
it is an attractive scaffold that can be utilized for exploiting
chemical diversity and generating a drug-like library to
screen for lead candidates.
Recent years have witnessed a considerable upsurge of inter-
est in the application of microwave (MW) irradiation as
a non-conventional energy source for the activation of
reactions, in solution and under solvent-free conditions in
particular, over the usual homogeneous and heterogeneous
reactions. Microwave irradiation provides chemical
2. Results and discussion
After some preliminary experimentation, it was found that
the synthesis of dithiazolopyrimidines 6 could be effected
by MW-activated solvent-free Michael addition of 3-imino-
1,4,2-dithiazoles 3 to 4-arylidene-5(4H)-oxazolones 4 to
Keywords: Microwaves; Thiourea; Diastereoselective synthesis; Dithiazolo-
pyrimidines; Michael addition.
* Corresponding author. Tel.: +91 5322500652; fax: +91 5322461157;
e-mail: ldsyadav@hotmail.com
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.04.033

L. D. S. Yadav, V. K. Rai / Tetrahedron 63 (2007) 6924–6931
6925
furnish adducts 5 regio- and diastereoselectively, which
underwent ring transformation to yield products 6 (route 1).
Alternatively, MW-activated Michael addition of isothio-
ureas 2 to 4-arylidene-5-(4H)-oxazolones 4 diastereo-
selectively afforded adducts 7, which underwent ring
transformation followed by heterocyclization via deoxyge-
native demethylation with thionyl chloride to yield regiose-
lectively the same products 6 (route 2). However, the highly
regio- and diastereoselective synthesis of target compound 6
is equally feasible by both routes.
(phenylmethane)sulfinylmethyl(phenylmethyl)thio-5,6-dihy-
dropyrimidin(4H)-4-ones 8 in 73–90% yields with >95:5
diastereoselectivity (Scheme 2). The compounds 8 under-
went heterocyclization via deoxygenative demethylation
with thionyl chloride in the presence of pyridine to give the
target compounds 6-acet(benz)amido-7-aryl-6,7-dihydro-
5H-1,4,2-dithiozolo[4,5-a]pyrimdin-5-ones 6 in 76–92%
yields with >95:5 diastereoselectivity and total regio-
control (Scheme 2).
For comparison purposes, the temperature of the reaction
mixture was maintained at 85 ꢀC in the case of the MW
method and the reactions were also carried out using a ther-
mostated oil-bath at the same temperature (85 ꢀC) of the
reaction mixture but for a longer (optimized) period of
time (Table 1). This was to ascertain whether the MW
method improves the yield and regio-/diastereoselectivity
or simply increases conversion rates. It was found that sig-
nificantly lower yields (35–48%) and diastereoselectivity
(>53:47) in route 1 and 34–50% yields and >56:44 dia-
stereoselectivity in route 2 were obtained using oil-bath
heating rather than the MW-activated method (Table 1).
However, total regiocontrol was observed in the MW-
activated method as well as by using oil-bath heating.
2.1. Route 1
The envisaged synthetic route in its entirety involves irradi-
ation of a mixture of 3-imino-1,4,2-dithiazoles 3 and 4-
arylidene-5(4H)-oxazolones 4 for 8–12 min in a CEM
Discover Focused Microwave Synthesis System at 85 ꢀC
(Table 1) to afford 6-acet(benz)amido-7-aryl-6,7-dihydro-
5H-1,3,4-dithiozolo[4,5-a]pyrimdin-5-ones 6 in 79–90%
yields with >96:4 diastereoselectivity (Table 1) and total re-
giocontrol (Scheme 1). The Michael adducts 5 were isolated
in 81–90% yields, with >96:4 diastereoselectivity (Table 1)
and total regiocontrol (Scheme 1). The procedure followed
was the same as that for 6 except that the time of MW irra-
diation in this case was 4 min.
This observation may be rationalized on the basis of the for-
mation of a dipolar transition state (TS) from an uncharged
ground state (GS) in these reactions (Schemes 1 and 2), and
the greater stabilization of more polar TS by dipole–dipole
interactions with the oscillating electric field of microwaves
as compared to the less polar GS, which may reduce the ac-
tivation energy (DGs) resulting in the rate enhancement.16
The formation of 6 involves the conjugate addition of the
2.2. Route 2
In an alternate route, the envisaged annulation was success-
ful with a mixture of isothioureas 2 and 4-arylidene-5(4H)-
oxazolones 4 under MW irradiation in a CEM Discover
Focused Microwave Synthesis System at 85 ꢀC for 4–8 min
(Table 1) to furnish 5-acet(benz)amido-6-aryl-2-methane-
Table 1. Microwave-activated synthesis of products 5–8
Product
Time
Thermal (h)b
Route 1
Route 2
Mp (ꢀC)
MW (min)a
Yield (%)c,d
cis:trans ratioe
Yield (%)c,d
cis:trans ratioe
MW Thermal
MW
Thermal
MW Thermal
MW
Thermal
5a
5e
5h
7a
7e
7h
6a
6b
6c
6d
6e
6f
6g
6h
8a
8b
8c
8d
8e
8f
4
4
4
6
6
3
2
2
3
2
3
4
6
6
5
5
6
4
4
3
2
3
3
2
2
2
3
90
81
85
—
—
—
79
81
90
83
89
79
88
90
—
—
—
—
—
—
—
—
49
35
45
—
—
—
35
37
48
41
45
39
44
38
—
—
—
—
—
—
—
—
98:2
59:41
57:43
53:47
—
—
—
55:45
55:45
56:46
54:46
55:45
54:46
57:43
56:44
—
—
—
—
—
—
—
—
—
—
—
77
87
74
89
76
92
78
82
87
79
85
78
88
90
75
85
73
87
74
—
—
—
42
44
38
50
48
52
34
39
36
44
46
41
48
51
46
44
38
50
39
—
—
—
—
—
—
177–178
217–218
185–186
146–147
208–210
167–168
160–162
139–140
145–146
155–157
197–199
163–164
188–189
166–167
131–133
115–116
143–144
151–152
190–192
170–171
178–179
148–150
98:2
97:3
—
—
—
97:3
97:3
98:2
99:1
99:1
97:3
98:2
98:2
—
—
—
—
—
—
—
—
96:4
97:3
97:3
96:4
97:3
96:4
97:3
97:3
96:4
99:1
99:1
96:4
97:3
97:3
96:4
98:2
99:1
98:2
98:2
59:41
57:43
58:42
60:40
57:43
58:42
58:42
57:43
58:42
59:41
59:41
59:41
57:43
52:48
51:49
57:43
51:49
52:48
58:42
6
8
10
10
8
10
12
12
10
4
4
6
8
8
6
8
4
8g
8h
a
Microwave irradiation time at 85 ꢀC.
Time for oil-bath heating at 85 ꢀC.
Yield of isolated and purified products.
b
c
d
e
All compounds gave C, H and N analyses within ꢁ0.32% and satisfactory spectral (IR, 1H NMR, 13C NMR and EIMS) data.
As determined by 1H NMR spectroscopy.

6926
L. D. S. Yadav, V. K. Rai / Tetrahedron 63 (2007) 6924–6931
NH2
R
O
S
S
C
SOCl2
i. NaOH/EtOH
O
ClCHSCH2R
S
S
Cl
HN
C
CH
R
CH2R
H2N
NH2
HN
C
Pyridine
S
O
H
O
2N
NH2
1
2
ii.
S
R
Cl
R
R = H, Ph
R
S
HN
C
-HCl
-SO2
-
R
Cl
S
Ar
N
MW
H
N
R
Cl
R
S
R'
HN
O
O
S
HN
3
4
uncharged GS
uncharged GS
S
δ
S
S
δ
N
H
N
N
R
N
R
R
N
O
N
δ
S
δ
O
S
S
N
H
N
H
R'
R'
NH
R'
O
O
5
uncharged GS
R'CONH
dipolar TS
dipolar TS
R'CONH
Ar
Ar
S
N
N
R
S
S
N
N
R
S
O
O
6'
6
2-6
a
R
R’ Ar
Ph Ph
2-6
e
R
R’ Ar
Me Ph
H
H
b
Ph Ph Ph
f
Ph Me Ph
Me 4-ClC6H4
Ph Me 4-ClC6H4
c
H
Ph 4-ClC6H4
g
H
d
Ph Ph 4-ClC6H4
h
Scheme 1.
ring nitrogen (N-2) of 3-imino-1,4,2-dithiazoles 3 to 4-aryl-
idene-5(4H)-oxazolones 4 via intermolecular nucleophilic
attack of the 3-imino nitrogen atom at the carbonyl carbon
(C-5) of oxazolones 4 followed by ring transformation of
the Michael adducts 5 to yield 6 (Scheme 1). Alternatively,
Michael addition of the nitrogen of isothioureas 2 to oxazo-
lones 4 gives adducts 7, which undergo ring transformation
followed by heterocyclization via deoxgenative demethyla-
tion with thionyl chloride to yield the title compounds 6
(Scheme 2).
than that leading to the trans isomers because, in general,
cis isomers are more polar than the trans isomers.29 How-
ever, we wish to make it clear that this explanation, based
on the tentative rationalization proposed by Loupy and
Perreux,16 is not substantiated and many experts in the field
may not agree to it.
It was found that there was no evolution of any trans form
under prolonged MW-induced and oil-bath heating of com-
pounds 6 at 85 ꢀC. This indicates that there is no equilibrium
between the cis and trans forms. The cis stereochemistry of
the products 6 was also supported by NOE experiments as
described below.
The formation of adducts 5 and 7 and their transformations
to 6 were highly diastereoselective in favour of the cis iso-
mers. The diastereomeric ratios of the crude products were
checked by 1H NMR prior to purification, to ensure accurate
and true diastereomeric ratios. The diastereomeric ratio for
compounds 6 in the case of MW activation was significantly
higher (>96:4 in route 1 and >95:5 in route 2) than that from
oil-bath heating (>53:47 in route 1 and >56:44 in route 2) as
The exclusive formation of regioisomers 6 instead of 60 is
mechanistically expected and further supported by the
NOE experiments. The 8% NOE at 7-H upon irradiation
of 2-H, combined with the absence of any measurable inten-
sity enhancement of 6-H signal, indicates that 7-H and 2-H
are located on the same face of the molecule, and that 2-H
is in closer spatial proximity with 7-H as compared with
6-H (Fig. 1). However, if the regioisomers 60 would have
been formed, then one would have expected almost the
same NOE at both 6-H and 7-H upon irradiation of 2-H be-
cause they are structurally almost at the same distance from
1
determined by H NMR spectroscopy. The high diastereo-
selectivity (>96% in route 1 and >95% in route 2) in favour
of the cis isomers under MW irradiation may be plausibly
explained by considering that MW irradiation favours the
reactions occurring via more polar TS16 and that the TS
leading to the formation of the cis isomers is more polar

L. D. S. Yadav, V. K. Rai / Tetrahedron 63 (2007) 6924–6931
6927
Ar
N
O
S
S
C
i. NaOH/EtOH
O
ClCHSCH2R
R'
S
O
CH
R
O
4
CH2R
H2N
NH2
HN
C
uncharged GS
MW
NH2
1
2
ii.
R
uncharged GS
R = H, Ph
δ
H
N
NH2
O
S
δ
O
S
NH
N
N
O
S
N
C
S
δ
δ
C S
NH
C S
O
NH
R'
R'
N
O
O
R'
O
R
R
O
H
O
R
R
R
R
7
dipolar TS
dipolar TS
uncharged GS
O
S
Cl
O
S
Ar
Ar
Cl
O
S
NH
N
SOCl2
NH
R
R'CONH
S
R'CONH
S
R
Pyridine
R
N
O
R
O
8
Cl
R
Ar
Ar
Ar
S
N
S
N
S
R
N
N
-
R
R
Cl
N
N
-HCl
-SO2
R'CONH
S
R'CONH
S
R'CONH
R
S
O
O
O
6
6'
2-8
a
R
R’ Ar
Ph Ph
2-8
e
R
R’ Ar
Me Ph
H
H
b
Ph Ph Ph
f
Ph Me Ph
c
H
Ph 4-ClC6H4
g
H
Me 4-ClC6H4
d
Ph Ph 4-ClC6H4
h
Ph Me 4-ClC6H4
Scheme 2.
NOE
4. Experimental
NOE
11%
8%
4.1. General
Ar
H
H
H
S
R
N
N
R'CONH
S
Melting points were determined in open glass capillaries and
are uncorrected. IR spectra in KBr were recorded on a
Perkin–Elmer 993 IR spectrophotometer. H NMR spectra
6
O
1
were recorded on a Bruker WM-40 C (400 MHz) FT spec-
trometer in DMSO-d6 using TMS as an 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 spec-
trometer. 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 for all the experiments. All chemicals
used were of reagent grade and were used as received with-
out further purification. Silica gel-G was used for TLC.
Figure 1.
2-H. Furthermore, the 11% NOE at 7-H (andw0% at 2-H)
upon irradiation of 6-H indicates that 6-H and 7-H are cis
to each other. The NOE experiments clearly indicate that
the R group in 6 is trans to 6-H and 7-H.
3. Conclusion
In summary, we have developed a general method for mild,
rapid and efficient regio- and diastereoselective synthesis of
potentially pharmaceutically and agrochemically useful
highly functionalized dithiazolopyrimidines starting from
thiourea employing microwave irradiations under solvent-
free conditions.
4.2. S-Methane(phenylmethane)sulfinylmethyl(phenyl-
methyl)isothioureas 2: general procedure
Chloromethyl methyl sulfoxide (2.2 mmol) was added to
a solution of NaOH (2.0 mmol) in ethanol (50 mL) and

6928
L. D. S. Yadav, V. K. Rai / Tetrahedron 63 (2007) 6924–6931
refluxed for 4–5 h. The solvent was evaporated and the resi-
due was washed well with H2O and recrystallized from
EtOH to give a product, which on second recrystallization
from EtOH furnished an analytically pure sample of 2 as
yellowish needles.
(>96:4, in the crude products the ratio was >94:6 as deter-
mined by 1H NMR spectroscopy). The product on second re-
crystallization from ethanol furnished an analytically pure
sample of a single diastereomer 6 (Table 1). On the basis
of comparison of J values to literature ones,30–35 and NOE
experiments (an NOE of w11% at 7-H upon irradiation of
6-H), the cis stereochemistry was assigned to 6, as the cou-
pling constant (J6,7¼5 Hz) of the major cis isomer was lower
than that for the minor trans diastereomer (J6,7¼10 Hz), and
there was no measurable intensity enhancement of 7-H sig-
nal upon irradiation of 6-H in case of the latter.
4.2.1. Compound 2a. Yield 65%, mp 176–177 ꢀC. IR (KBr)
1
nmax 3390, 3360, 1635, 1030 cmꢂ1. H NMR (DMSO-d6/
TMS) d: 2.31 (br s, 3H, NH2 and ]NH exchanges with
D2O), 2.56 (s, 3H, Me), 4.28 (s, 2H, CH2). 13C NMR
(DMSO-d6/TMS) d: 35.2 (Me), 48.8 (CH2), 162.9 (C]N).
Mass (m/z): 152 (M+). Anal. Calcd for C3H8N2OS2: C,
23.67; H, 5.30; N, 18.40%. Found: C, 23.91; H, 5.17; N,
18.53%.
Route 2: the procedure followed was the same as described
above for the synthesis of 3, except that the starting material
in this case was 5,6-dihydroyrimidin(4H)-4-ones 8 instead
of isothioureas 2 (2.0 mmol) for 3. Pyridine was evaporated
under reduced pressure and the residue was washed with
water to give crude product (diastereomeric ratio >92:8).
To obtain analytically pure sample of 6 (diastereomeric ratio
>95:5) the same procedure was adopted as described in
route 1.
4.2.2. Compound 2b. Yield 73%, mp 152–153 ꢀC. IR (KBr)
1
nmax 3393, 3362, 1632, 1605, 1585, 1453, 1030 cmꢂ1. H
NMR (DMSO-d6/TMS) d: 2.5 (br s, 3H, NH2 and ]NH
exchanges with D2O), 3.80 (s, 2H, PhCH2), 4.58 (s, 1H,
CHPh), 7.02–8.12 (m, 10Harom). 13C NMR (DMSO-d6/
TMS) d: 53.5 (CH2Ph), 61.8 (CHPh), 128.1, 129.0, 129.8,
130.5, 131.2, 131.9, 132.6, 133.0 (2ꢃPh), 163.1 (C]N).
Mass (m/z): 304 (M+). Anal. Calcd for C15H16N2OS2: C,
59.18; H, 5.30; N, 9.20%. Found: C, 58.83; H, 5.51; N,
9.07%.
4.4.1. Compound 6a. Yellowish needles, mp 160–162 ꢀC.
IR (KBr) nmax 3340, 3023, 1745, 1642, 1633, 1603, 1586,
1457 cmꢂ1. 1H NMR (DMSO-d6/TMS) d: 4.21 (s, 2H, CH2),
6.60 (d, 1H, J¼5 Hz, H-6), 6.72 (dd, 1H, J¼5, 10 Hz, H-5),
7.34–8.20 (m, 10Harom), 8.60 (br s, 1H, NHacyclic, exchanges
with D2O). 13C NMR (DMSO-d6/TMS) d: 51.0 (CH2), 59.9
(6-C), 60.2 (5-C), 126.1, 127.2, 128.4, 129.6, 130.4, 131.3,
132.1, 133.0 (2ꢃPh), 163.0 (SC]N), 167.9, 177.0 (2ꢃC]
O). Mass (m/z): 369 (M+). Anal. Calcd for C18H15N3O2S2:
C, 58.52; H, 4.09; N, 11.37%. Found: C, 58.80; H, 4.27;
N, 11.22%.
4.3. 3-Imino-1,4,2-dithiazoles 3: general procedure
A solution of isothioureas (2.0 mmol) and thionyl chloride
(2.5 mmol) in pyridine was refluxed for 8 h. Pyridine was
evaporated under reduced pressure and the residue was
washed with water to give crude product, which was recrys-
tallized from ethanol to obtain the analytically pure sample
of 3.
4.4.2. Compound 6b. Yellowish needles, mp 139–140 ꢀC.
IR (KBr) nmax 3342, 3025, 1743, 1651, 1629, 1601, 1581,
4.3.1. Compound 3a. Yield 74%, mp 160–161 ꢀC. IR (KBr)
nmax 3375, 1640 cmꢂ1. 1H NMR (DMSO-d6/TMS) d: 2.5 (br
s, 2H, NH2 exchanges with D2O), 4.18 (s, 2H, CH2). 13C
NMR (DMSO-d6/TMS) d: 19.7 (CH2), 163.0 (C]N). Mass
(m/z): 120 (M+). Anal. Calcd for C2H4N2S2: C, 19.99; H,
3.35; N, 23.31%. Found: C, 20.25; H, 3.19; N, 23.63%.
1452 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 4.48 (s, 1H,
.
CHPh), 6.61 (d, 1H, J¼5 Hz, H-6), 6.73 (dd, 1H, J¼5, 10 Hz,
H-5), 7.28–7.99 (m, 15Harom), 8.61 (br s, 1H, NHacyclic, ex-
changes with D2O). 13C NMR (DMSO-d6/TMS) d: 53.7
(CHPh), 60.5 (6-C), 61.2 (5-C), 126.3, 127.0, 128.1, 128.8,
129.5, 130.2, 131.0, 131.6, 132.3, 133.1, 134.0, 134.8
(3ꢃPh), 162.8 (SC]N), 168.1, 180.0 (2ꢃC]O). Mass
(m/z): 445 (M+). Anal. Calcd for C24H19N3O2S2: C, 64.70;
H, 4.30; N, 9.43%. Found: C, 64.38; H, 4.11; N, 9.55%.
4.3.2. Compound 3b. Yield 70%, mp 149–150 ꢀC. IR (KBr)
nmax 3385, 1633, 1603, 1581, 1455 cmꢂ1. 1H NMR (DMSO-
d6/TMS) d: 2.2 (br s, 2H, NH2 exchanges with D2O), 4.75 (s,
1H, CHPh), 7.68–7.86 (m, 5Harom). 13C NMR (DMSO-d6/
TMS) d: 37.0 (CHPh), 126.7, 127.8, 128.6, 130.8 (Ph), 164.2
(C]N). Mass (m/z): 196 (M+). Anal. Calcd for C8H8N2S2:
C, 48.95; H, 4.11; N, 14.27%. Found: C, 48.71; H, 4.40;
N, 14.09%.
4.4.3. Compound 6c. Yellowish needles, mp 145–146 ꢀC.
IR (KBr) nmax 3347, 3021, 1747, 1641, 1628, 1599, 1580,
1453 cmꢂ1. 1H NMR (DMSO-d6/TMS) d: 4.24 (s, 2H, CH2),
6.60 (d, 1H, J¼5 Hz, H-6), 6.76 (dd, 1H, J¼5, 10 Hz, H-5),
7.31–8.24 (m, 9Harom), 8.56 (br s, 1H, NHacyclic, exchanges
with D2O). 13C NMR (DMSO-d6/TMS) d: 50.8 (CH2), 59.7
(6-C), 60.1 (5-C), 126.5, 127.3, 128.9, 129.6, 130.5, 131.2,
132.0, 133.0 (Ph, 4-ClC6H4), 162.9 (SC]N), 167.7, 179.9
(2ꢃC]O). Mass (m/z): 403, 405 (M, M+2). Anal. Calcd
for C18H14ClN3O2S2: C, 53.53; H, 3.49; N, 10.40%. Found:
C, 53.35; H, 3.68; N, 10.29%.
4.4. 6-Acet(benz)amido-7-aryl-6,7-dihydro-5H-1,3,4-
dithiozolo[4,5-a]pyrimidin-5-ones 6: general procedure
Route 1: thoroughly mixed 4-arylidene-5(4H)-oxazolones 4
(1.0 mmol) and 3-imino-1,4,2-dithiazoles 3 (1.0 mmol) was
taken in a 20 mL vial and subjected to MW irradiation at
85 ꢀC for 8–12 min (Table 1). After completion of the reac-
tion 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-
lized from ethanol to afford a diastereomeric mixture
4.4.4. Compound 6d. Yellowish needles, mp 155–157 ꢀC.
IR (KBr) nmax 3341, 3018, 1744, 1644, 1635, 1597, 1585,
1455 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 4.50 (s, 1H,
.
CHPh), 6.63 (d, 1H, J¼5 Hz, H-6), 6.75 (dd, 1H, J¼5,
10 Hz, H-5), 7.31–8.10 (m, 14Harom), 8.63 (br s, 1H,

L. D. S. Yadav, V. K. Rai / Tetrahedron 63 (2007) 6924–6931
6929
NHacyclic, exchanges with D2O). 13C NMR (DMSO-d6/
TMS) d: 53.5 (CHPh), 60.3 (6-C), 61.6 (5-C), 126.0,
127.1, 127.8, 128.0, 129.1, 129.6, 130.3, 131.1, 132.0, 132.6,
133.4, 134.5 (2ꢃPh, 4-ClC6H4), 163.2 (SC]N), 168.2,
180.5 (2ꢃC]O). Mass (m/z): 479, 481 (M, M+2). Anal.
Calcd for C24H18ClN3O2S2: C, 60.05; H, 3.78; N, 8.75%.
Found: C, 60.37; H, 3.93; N, 8.69%.
this case was 4 min instead of 8–12 min for 6 (route 1). Ad-
ducts 5 were recrystallized from ethanol to give a diastereo-
meric mixture (>96:4, in the crude isolates the ratio was
1
>94:6 as determined by H NMR spectroscopy), which
was again recrystallized from ethanol to obtain an analytical
sample of 5a, 5e and 5h. Adducts 5a, 5e and 5h were as-
signed the syn stereochemistry, as their 1H NMR spectra ex-
hibited lower values of coupling constant Jcyclic NCH, Jacyclic
4.4.5. Compound 6e. Yellowish needles, mp 197–199 ꢀC.
IR (KBr) nmax 3345, 3025, 1748, 1652, 1634, 1604, 1583,
¼5 Hz, than that of the very minor (<4%) diastereomer
NCH
(anti), Jcyclic NCH, Jacyclic NCH¼9 Hz.30–35 Finely powdered
intermediate compounds 5a, 5e and 5h were MW irradiated
for 6 min in the same way as described for the synthesis of 6
(route 1) to give the corresponding annulated products 6a, 6e
and 6h quantitatively.
1458 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 2.12 (s, 3H,
.
Me), 4.18 (s, 2H, CH2), 6.63 (d, 1H, J¼5 Hz, H-6), 6.67
(dd, 1H, J¼5, 10 Hz, H-5), 7.35–8.29 (m, 5Harom), 8.54 (br
s, 1H, NHacyclic, exchanges with D2O). 13C NMR (DMSO-
d6/TMS) d: 21.2 (Me), 50.6 (CH2), 59.5 (6-C), 60.0 (5-C),
127.0, 129.9, 132.1, 133.5 (Ph), 162.7 (SC]N), 167.3,
181.2 (2ꢃC]O). Mass (m/z): 307 (M+). Anal. Calcd for
C13H13N3O2S2: C, 50.79; H, 4.26; N, 13.67%. Found: C,
50.57; H, 4.43; N, 13.52%.
4.5.1. Compound 5a. Pale yellow needles, mp 177–178 ꢀC.
IR (KBr) nmax 3342, 3020, 1746, 1632, 1603, 1580,
1450 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 4.23 (s, 2H,
.
CH2), 6.67 (d, 1H, J¼5 Hz, acyclic NCH), 6.78 (d, 1H,
J¼5 Hz, cyclic NCH), 7.11–7.90 (m, 10Harom), 8.45 (br s,
1H, NH, exchanges with D2O). 13C NMR (DMSO-d6/
TMS) d: 51.3 (CH2), 64.4 (Ar-C), 69.7 (O]C–C), 126.2,
126.9, 127.9, 129.0, 129.6, 130.3, 131.0, 132.5 (2ꢃPh),
159.2 (SC]N), 160.7 (OC]N), 172.5 (C]O). Mass (m/z):
369 (M+). Anal. Calcd for C18H15N3O2S2: C, 58.52; H,
4.09; N, 11.37%. Found: C, 58.84; H, 4.31; N, 11.21%.
4.4.6. Compound 6f. Yellowish needles, mp 163–164 ꢀC. IR
(KBr) nmax 3340, 3027, 1742, 1648, 1628, 1602, 1582,
1451 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 2.14 (s, 3H,
.
Me), 4.47 (s, 1H, CHPh), 6.62 (d, 1H, J¼5 Hz, H-6), 6.74
(dd, 1H, J¼5, 10 Hz, H-5), 7.30–8.21 (m, 10Harom), 8.59 (br
s, 1H, NHacyclic, exchanges with D2O). 13C NMR (DMSO-
d6/TMS) d: 21.5 (Me), 51.3 (CHPh), 59.8 (6-C), 62.1 (5-
C), 126.8, 127.6, 128.4, 129.1, 130.0, 130.7, 131.9, 133.0
(2ꢃPh), 162.9 (SC]N), 168.0, 182.3 (2ꢃC]O). Mass
(m/z): 383 (M+). Anal. Calcd for C19H17N3O2S2: C, 59.51;
H, 4.47; N, 10.96%. Found: C, 59.79; H, 4.19; N, 10.79%.
4.5.2. Compound 5e. Pale yellow needles, mp 217–218 ꢀC.
IR (KBr) nmax 3340, 3021, 1742, 1630, 1601, 1578,
1455 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 2.15 (s, 3H,
.
Me), 4.25 (s, 2H, CH2), 6.65 (d, 1H, J¼5 Hz, acyclic
NCH), 6.77 (d, 1H, J¼5 Hz, cyclic NCH), 7.08–7.91 (m,
5Harom), 8.46 (br s, 1H, NH, exchanges with D2O). 13C
NMR (DMSO-d6/TMS) d: 20.3 (Me), 51.1 (CH2), 64.2
(Ar-C), 69.5 (O]C–C), 126.0, 127.5, 130.0, 132.7 (Ph),
159.0 (SC]N), 160.8 (OC]N), 172.1 (C]O). Mass
(m/z): 307 (M+). Anal. Calcd for C13H13N3O3S2: C, 50.79;
H, 4.26; N, 13.67%. Found: C, 50.51; H, 4.41; N, 13.52%.
4.4.7. Compound 6g. Yellowish needles, mp 188–189 ꢀC.
IR (KBr) nmax 3343, 3020, 1746, 1643, 1631, 1598, 1579,
1450 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 2.15 (s, 3H,
.
Me), 4.21 (s, 2H, CH2), 6.62 (d, 1H, J¼5 Hz, H-6), 6.68
(dd, 1H, J¼5, 10 Hz, H-5), 7.34–8.26 (m, 4Harom), 8.55 (br
s, 1H, NHacyclic, exchanges with D2O). 13C NMR (DMSO-
d6/TMS) d: 21.4 (Me), 51.2 (CH2), 59.6 (6-C), 62.5 (5-C),
126.1, 127.4, 131.4, 133.1 (4-ClC6H4), 163.0 (SC]N),
168.0, 182.1 (2ꢃC]O). Mass (m/z): 341, 343 (M, M+2).
Anal. Calcd for C13H12ClN3O2S2: C, 45.68; H, 3.54; N,
12.29%. Found: C, 45.93; H, 3.29; N, 12.41%.
4.5.3. Compound 5h. Pale yellow needles, mp 185–186 ꢀC.
IR (KBr) nmax 3344, 3024, 1747, 1635, 1605, 1585,
1451 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 2.33 (s, 3H,
.
Me), 4.50 (s, 1H, CHPh), 6.68 (d, 1H, J¼5 Hz, acyclic
NCH), 6.79 (d, 1H, J¼5 Hz, cyclic NCH), 7.30–8.08 (m,
9Harom), 8.48 (br s, 1H, NH, exchanges with D2O). 13C
NMR (DMSO-d6/TMS) d: 20.5 (Me), 53.8 (CHPh), 64.7
(Ar-C), 70.1 (O]C–C), 126.5, 127.3, 128.8, 129.7, 130.5,
131.4, 132.0, 132.9 (Ph, 4-ClC6H4), 159.8 (SC]N), 160.9
(OC]N), 172.3 (C]O). Mass (m/z): 417, 419 (M, M+2).
Anal. Calcd for C19H16ClN3O3S2: C, 54.60; H, 3.86; N,
10.05%. Found: C, 54.89; H, 3.73; N, 10.17%.
4.4.8. Compound 6h. Yellowish needles, mp 166–167 ꢀC.
IR (KBr) nmax 3346, 3022, 1745, 1647, 1630, 1600, 1583,
1455 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 2.16 (s, 3H,
.
Me), 4.49 (s, 1H, CHPh), 6.63 (d, 1H, J¼5 Hz, H-6), 6.71
(dd, 1H, J¼5, 10 Hz, H-5), 7.26–8.09 (m, 9Harom), 8.64 (br
s, 1H, NHacyclic, exchanges with D2O). 13C NMR (DMSO-
d6/TMS) d: 21.7 (Me), 51.5 (CHPh), 60.1 (6-C), 62.8 (5-
C), 126.5, 127.2, 128.0, 129.1, 129.7, 131.3, 132.2, 133.8
(Ph, 4-ClC6H4), 163.2 (SC]N), 168.2, 182.3 (2ꢃC]O).
Mass (m/z): 417, 419 (M, M+2). Anal. Calcd for
C19H16ClN3O2S2: C, 54.60; H, 3.86; N, 10.05%. Found: C,
54.92; H, 4.05; N, 9.97%.
4.6. 5-Acet(benz)amido-6-aryl-2-methane(phenyl-
methane)sulfinylmethyl(phenylmethyl)thio-5,6-dihy-
dropyrimidin(4H)-4-ones 8: general procedure
A mixture of isothioureas 2 (1.0 mmol) and 4-arylidene-
5(4H)-oxazolones 4 (1.0 mmol) was taken in a 20 mL vial
and subjected to MW irradiation at 85 ꢀC for 4–8 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 precip-
itate thus obtained was washed with water to give the crude
4.5. Isolation of Michael adducts 5a, 5e and 5h and their
transformation into the corresponding final products 6a,
6e and 6h: general procedure
The procedure followed was the same as described above for
the synthesis of 6 except that the time of MW irradiation in

6930
L. D. S. Yadav, V. K. Rai / Tetrahedron 63 (2007) 6924–6931
product, which was recrystallized from ethanol to afford
a diastereomeric mixture (>95:5, in the crude products the
ratio was >92:8 as determined by H NMR spectroscopy).
126.0, 126.7, 127.3, 128.0, 128.6, 129.2, 129.9, 130.6,
131.2, 132.0, 132.7, 133.3, 134.0, 134.7, 135.3, 136.0 (3ꢃ
Ph, 4-ClC6H4), 160.5 (SC]N), 170.5, 172.3 (2ꢃC]O).
Mass (m/z): 587, 589 (M, M+2). Anal. Calcd for
C31H26ClN3O3S2: C, 63.31; H, 4.46; N, 7.14%. Found: C,
63.12; H, 4.66; N, 7.27%.
1
The product on second recrystallization from ethanol fur-
nished an analytically pure sample of a single diastereomer
8 (Table 1). On the basis of comparison of J values to liter-
ature ones,30–35 and NOE experiments (an NOE of w10%
at 5-H upon irradiation of 6-H), the cis stereochemistry
was assigned to 8, as the coupling constant (J5,6¼4 Hz) of
the major cis isomer was lower than that for the minor trans
diastereomer (J5,6¼8 Hz), and there was no measurable in-
tensity enhancement of 5-H signal upon irradiation of 6-H
in case of the latter.
4.6.5. Compound 8e. Yellowish needles, mp 190–192 ꢀC.
IR (KBr) nmax 3338, 3018, 1749, 1641, 1630, 1603, 1578,
1448 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 2.15 (s, 3H,
.
MeCO), 2.61 (s, 3H, MeSO), 4.24 (s, 2H, CH2), 6.57 (d,
1H, J¼5 Hz, H-6), 6.69 (dd, 1H, J¼5, 10 Hz, H-5), 7.31–
8.26 (m, 5Harom), 8.42 (br s, 1H, cyclic NH, exchanges
with D2O), 8.55 (br s, 1H, acyclic NH, exchanges with
D2O). 13C NMR (DMSO-d6/TMS) d: 21.3 (MeC]O),
41.3(MeS]O), 58.2 (CH2), 60.1 (6-C), 64.5 (5-C), 127.5,
129.4, 131.5, 132.8 (Ph), 160.3 (SC]N), 171.0, 173.5 (2ꢃ
C]O). Mass (m/z): 339 (M+). Anal. Calcd for
C14H17N3O3S2: C, 49.54; H, 5.05; N, 12.38%. Found: C,
49.86; H, 5.27; N, 12.22%.
4.6.1. Compound 8a. Yellowish needles, mp 131–133 ꢀC.
IR (KBr) nmax 3341, 3021, 1748, 1645, 1632, 1605, 1580,
1455 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 2.58 (s, 3H,
.
Me), 4.21 (s, 2H, CH2), 6.60 (d, 1H, J¼5 Hz, H-6), 6.72
(dd, 1H, J¼5, 10 Hz, H-5), 7.31–8.23 (m, 10Harom), 8.43
(br s, 1H, cyclic NH, exchanges with D2O), 8.62 (br s, 1H,
acyclic NH, exchanges with D2O). 13C NMR (DMSO-d6/
TMS) d: 41.2 (MeS]O), 58.0 (CH2), 59.5 (6-C), 64.2 (5-
C), 126.7, 127.5, 128.8, 129.5, 130.2, 130.9, 131.7, 132.8
(2ꢃPh), 159.5 (SC]N), 170.1, 172.6 (2ꢃC]O). Mass
(m/z): 401 (M+). Anal. Calcd for C19H19N3O3S2: C, 56.84;
H, 4.77; N, 10.47%. Found: C, 56.52; H, 4.55; N, 10.31%.
4.6.6. Compound 8f. Yellowish needles, mp 170–171 ꢀC. IR
(KBr) nmax 3339, 3020, 1747, 1640, 1629, 1604, 1581,
1450 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 2.17 (s, 3H,
.
MeC]O), 2.81 (s, 2H, CH2), 4.49 (s, 1H, SCH), 6.61 (d,
1H, J¼5 Hz, H-6), 6.73 (dd, 1H, J¼5, 10 Hz, H-5), 7.30–
8.15 (m, 15Harom), 8.53 (br s, 1H, cyclic NH, exchanges
with D2O), 8.40 (br s, 1H, acyclic NH, exchanges with
D2O). 13C NMR (DMSO-d6/TMS) d: 21.5 (Me), 51.4 (CH2),
58.1 (S]OCH), 60.3 (6-C), 64.2 (5-C), 126.3, 127.0, 127.8,
128.6, 129.7, 130.5, 131.2, 132.0, 132.7, 133.1, 133.7, 134.3
(3ꢃPh), 160.3 (SC]N), 170.7, 172.9 (2ꢃC]O). Mass
(m/z): 491 (M+). Anal. Calcd for C26H25N3O3S2: C, 63.52;
H, 5.13; N, 8.55%. Found: C, 63.81; H, 5.29; N, 8.39%.
4.6.2. Compound 8b. Yellowish needles, mp 115–116 ꢀC.
IR (KBr) nmax 3343, 3022, 1747, 1646, 1635, 1603, 1585,
1459 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 2.85 (s, 2H,
.
CH2), 4.53 (s, 1H, SCH), 6.65 (d, 1H, J¼5 Hz, H-6), 6.71
(dd, 1H, J¼5, 10 Hz, H-5), 7.20–7.98 (m, 20Harom), 8.66
(br s, 1H, cyclic NH, exchanges with D2O), 8.44 (br s, 1H,
acyclic NH, exchanges with D2O). 13C NMR (DMSO-d6/
TMS) d: 51.5 (CH2), 58.0 (S]OCH), 60.1 (6-C), 64.5 (5-
C), 126.2, 126.8, 127.5, 128.1, 128.9, 129.5, 130.1, 130.8,
131.2, 131.8, 132.5, 133.2, 134.0, 134.6, 135.1, 135.8
(4ꢃPh), 160.2 (SC]N), 170.2, 172.8 (2ꢃC]O). Mass
(m/z): 553 (M+). Anal. Calcd for C31H27N3O3S2: C, 67.24;
H, 4.92; N, 7.59%. Found: C, 67.51; H, 4.71; N, 7.44%.
4.6.7. Compound 8g. Yellowish needles, mp 178–179 ꢀC.
IR (KBr) nmax 3341, 3022, 1748, 1642, 1630, 1605, 1580,
1455 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 2.18 (s, 3H,
.
MeC]O), 2.58 (s, 3H, MeS]O), 4.20 (s, 2H, CH2), 6.63
(d, 1H, J¼5 Hz, H-6), 6.72 (dd, 1H, J¼5, 10 Hz, H-5),
7.22–8.26 (m, 4Harom), 8.45 (br s, 1H, cyclic NH, exchanges
with D2O), 8.57 (br s, 1H, acyclic NH, exchanges with D2O).
13C NMR (DMSO-d6/TMS) d: 21.4 (MeC]O), 41.5
(MeS]O), 58.5 (CH2), 60.8 (6-C), 64.9 (5-C), 127.9,
129.5, 132.2, 133.8 (4-ClC6H4), 160.1 (SC]N), 170.9,
173.1 (2ꢃC]O). Mass (m/z): 373, 375 (M, M+2). Anal.
Calcd for C14H16ClN3O3S2: C, 44.97; H, 4.31; N, 11.24%.
Found: C, 45.29; H, 4.06; N, 11.09%.
4.6.3. Compound 8c. Yellowish needles, mp 143–144 ꢀC.
IR (KBr) nmax 3347, 3025, 1751, 1650, 1634, 1608, 1588,
1461 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 2.55 (s, 3H,
.
Me), 4.19 (s, 2H, CH2), 6.63 (d, 1H, J¼5 Hz, H-6), 6.69
(dd, 1H, J¼5, 10 Hz, H-5), 7.34–8.21 (m, 9Harom), 8.41
(br s, 1H, cyclic NH, exchanges with D2O), 8.65 (br s, 1H,
acyclic NH, exchanges with D2O). 13C NMR (DMSO-d6/
TMS) d: 41.4 (MeS]O), 58.4 (CH2), 60.5 (6-C), 64.8 (5-
C), 126.4, 127.2, 128.1, 128.8, 129.5, 130.3, 131.7, 133.8
(Ph, 4-ClC6H4), 160.5 (SC]N), 170.6, 173.2 (2ꢃC]O).
Mass (m/z): 435, 437 (M, M+2). Anal. Calcd for
C19H18ClN3O3S2: C, 52.35; H, 4.16; N, 9.64%. Found: C,
52.08; H, 4.36; N, 9.48%.
4.6.8. Compound 8h. Yellowish needles, mp 148–150 ꢀC.
IR (KBr) nmax 3343, 3021, 1746, 1643, 1633, 1603, 1583,
1453 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 2.19 (s, 3H,
.
MeCO), 2.83 (s, 2H, CH2), 4.51 (s, 1H, SCH), 6.64 (d, 1H,
J¼5 Hz, H-6), 6.76 (dd, 1H, J¼5, 10 Hz, H-5), 7.31–8.32
(m, 14Harom), 8.54 (br s, 1H, cyclic NH, exchanges with
D2O), 8.39 (br s, 1H, acyclic NH, exchanges with D2O).
13C NMR (DMSO-d6/TMS) d: 21.7 (Me), 51.6 (CH2), 58.3
(S]OCH), 60.5 (6-C), 64.7 (5-C), 126.7, 127.4, 127.2,
129.0, 129.6, 130.3, 131.0, 131.8, 132.4, 133.2, 134.0, 134.6
(2ꢃPh, 4-ClC6H4), 160.7 (SC]N), 170.5, 173.2 (2ꢃC]O).
Mass (m/z): 525, 527 (M, M+2). Anal. Calcd for
C26H24ClN3O3S2: C, 59.36; H, 4.60; N, 7.99%. Found: C,
59.65; H, 4.41; N, 7.89%.
4.6.4. Compound 8d. Yellowish needles, mp 151–152 ꢀC.
IR (KBr) nmax 3345, 3027, 1750, 1652, 1635, 1607, 1589,
1460 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 2.88 (s, 2H,
.
CH2), 4.55 (s, 1H, SCH), 6.68 (d, 1H, J¼5 Hz, H-6), 6.75
(dd, 1H, J¼5, 10 Hz, H-5), 7.28–8.11 (m, 19Harom), 8.67
(br s, 1H, cyclic NH, exchanges with D2O), 8.48 (br s, 1H,
acyclic NH, exchanges with D2O). 13C NMR (DMSO-d6/
TMS) d: 52.5 (CH2), 58.5 (S]OCH), 60.2 (6-C), 64.7 (5-C),

L. D. S. Yadav, V. K. Rai / Tetrahedron 63 (2007) 6924–6931
6931
4.7. Isolation of Michael adducts 7a, 7e and 7h and their
transformation into the corresponding products 8a, 8e
and 8h
References and notes
1. Senga, K.; Novinson, T.; Wilson, H. R.; Robins, R. J. Med.
Chem. 1981, 24, 610–613.
The procedure followed was the same as described above for
the isolation of 5a, 5e and 5h but the time of MW irradiation
in this case was 3 min instead of 4 min. To obtain analyti-
cally pure sample of 7a, 7e and 7h (diastereomeric ratio
>95:5) and to assign the stereochemistry the same procedure
was adopted as described for 5a, 5e and 5h. Finely powdered
intermediate compounds 7a, 7e and 7h were MW irradiated
for 5 min in the same way as described for the synthesis of 8
to give the corresponding annulated products 8a, 8e and 8h
quantitatively.
2. Bernier, J. L.; Henichart, J. P.; Warin, V.; Baert, F. J. Pharm.
Sci. 1980, 69, 1343–1345.
3. Yadav, L. D.S.;Pal, D. R. IndianJ. Chem.1997, 36B, 1034–1037.
4. Holla, B. S.; Rao, B. S.; Sarojini, B. K.; Akberali, P. M. Eur. J.
Med. Chem. 2004, 39, 777–783.
5. Fahmy, H. T.; Rostom, S. A.; Bekit, A. A. Arch. Pharm. Pharm.
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4.7.1. Compound 7a. Pale yellow needles, mp 146–147 ꢀC.
IR (KBr) nmax 3344, 3025, 1745, 1631, 1604, 1581,
1
1458 cmꢂ1. H NMR (DMSO-d6/TMS) d: 2.30 (br s, 2H,
NH2, exchanges with D2O), 2.55 (s, 3H, Me), 4.26 (s, 2H,
CH2), 6.65 (d, 1H, J¼5 Hz, acyclic NCH), 6.79 (d, 1H,
J¼5 Hz, cyclic NCH), 7.05–7.88 (m, 10Harom). 13C NMR
(DMSO-d6/TMS) d: 41.0 (MeS]O), 57.7 (CH2), 64.6 (Ar-
C), 69.8 (O]C–C), 126.2, 127.0, 128.8, 129.5, 130.3,
131.0, 132.1, 133.0 (2ꢃPh), 160.5 (OC]N), 162.5
(SC]N), 172.3 (C]O). Mass (m/z): 401 (M+). Anal. Calcd
for C19H19N3O3S2: C, 56.84; H, 4.77; N, 10.47%. Found: C,
57.09; H, 4.65; N, 10.29%.
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19. Meshram, H. M.; Shekhar, K. C.; Ganesh, Y. S. S.; Yadav, J. S.
Synlett 2000, 1273–1275.
4.7.2. Compound 7e. Pale yellow needles, mp 208–210 ꢀC.
IR (KBr) nmax 3342, 3024, 1746, 1635, 1601, 1578,
1453 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 2.16 (s, 3H,
.
MeC]N), 2.32 (br s, 2H, NH2, exchanges with D2O),
2.51 (s, 3H, MeS]O), 4.23 (s, 2H, CH2), 6.64 (d,
1H, J¼5 Hz, acyclic NCH), 6.78 (d, 1H, J¼5 Hz, cyclic
NCH), 7.15–7.79 (m, 5Harom). 13C NMR (DMSO-d6/
TMS) d: 20.2 (MeC]N), 41.2 (MeS]O), 57.8 (CH2),
64.3 (Ar-C), 69.7 (O]C–C), 126.5, 128.2, 130.3, 132.5
(Ph), 160.6 (OC]N), 162.3 (SC]N), 172.1 (C]O).
Mass (m/z): 339 (M+). Anal. Calcd for C14H17N3O3S2: C,
49.54; H, 5.05; N, 12.38%. Found: C, 49.29; H, 5.26; N,
12.24%.
20. Strohmeier, G. A.; Kappe, C. O. J. Comb. Chem. 2002, 4,
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Besson, T. Mol. Divers. 2003, 7, 273–280.
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35, 717–727.
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455–458.
27. Yadav, L. D. S.; Kapoor, R. Synlett 2005, 3055–3058.
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29. Eliel, E. L.; Wilen, S. H.; Mander, L. N. Stereochemistry of
Organic Compounds; Wiley: New York, NY, 2003; pp 672–673.
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491–494.
4.7.3. Compound 7h. Pale yellow needles, mp 167–168 ꢀC.
IR (KBr) nmax 3345, 3027, 1742, 1633, 1605, 1585,
1455 cmꢂ1 1H NMR (DMSO-d6/TMS) d: 2.18 (s, 3H,
.
Me), 2.35 (br s, 2H, NH2, exchanges with D2O), 2.85 (s,
2H, CH2), 4.55 (s, 1H, SCH), 6.67 (d, 1H, J¼5 Hz, acyclic
NCH), 6.81 (d, 1H, J¼5 Hz, cyclic NCH), 7.35–7.48 (m,
14Harom). 13C NMR (DMSO-d6/TMS) d: 20.5 (Me), 53.7
(CH2Ph), 62.0 (CHPh), 64.7 (Ar-C), 70.1 (O]C–C),
126.8, 127.7, 128.5, 129.2, 130.0, 131.2, 132.1, 133.0 (Ph,
4-ClC6H4), 160.8 (OC]N), 162.7 (SC]N), 172.5
(C]O). Mass (m/z): 525, 527 (M, M+2). Anal. Calcd for
C26H24ClN3O3S2: C, 59.36; H, 4.60; N, 7.99%. Found: C,
59.62; H, 4.45; N, 8.07%.
Acknowledgements
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5464–5468.
We sincerely thank SAIF, Punjab University, Chandigarh,
for providing microanalyses and spectra.