The first ionic liquid-promoted one-pot diastereoselective synthesis of 2,5-diamino-/2-amino-5-mercapto-1,3-thiazin-4-ones using masked amino/mercapto acids

Article abstract of DOI:10.1016/j.tet.2008.12.050

The first expeditious synthesis of 2,5-diamino-/2-amino-5-mercapto-1,3-thiazin-4-ones from masked and activated amino/mercapto acids, viz. 2-phenyl-1,3-oxazol-5-one or 2-methyl-2-phenyl-1,3-oxathiolan-5-one, aromatic aldehydes and thioureas using the ioni

Full text of DOI:10.1016/j.tet.2008.12.050

Tetrahedron 65 (2009) 1306–1315
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
The first ionic liquid-promoted one-pot diastereoselective synthesis
of 2,5-diamino-/2-amino-5-mercapto-1,3-thiazin-4-ones using masked
amino/mercapto acids
*
Lal Dhar S. Yadav , Vijai K. Rai, Beerendra S. Yadav
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211 002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 October 2008
Received in revised form 5 December 2008
Accepted 12 December 2008
Available online 24 December 2008
The first expeditious synthesis of 2,5-diamino-/2-amino-5-mercapto-1,3-thiazin-4-ones from masked
and activated amino/mercapto acids, viz. 2-phenyl-1,3-oxazol-5-one or 2-methyl-2-phenyl-1,3-oxa-
thiolan-5-one, aromatic aldehydes and thioureas using the ionic liquid [Bmim]Br as an environmentally
benign reaction promoter is reported. The synthesis is highly diastereoselective and involves tandem
Knoevenagel, Michael and ring transformation reactions in a one-pot procedure. The sequential reaction
pathway is supported by the isolation of arylidene derivatives and their Michael adducts with thiourea,
and quantitative conversion of the latter into the final products under the same reaction conditions.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Ionic liquids
1,3-Thiazines
Stereoselective synthesis
Thiourea
Oxazolone
Oxathiolanone
1. Introduction
1,3-thiazines incorporating 2,5-diamino or 2-amino-5-mercapto
functionalities although they appear as attractive scaffolds to be
Over the past decade, industrial and academic researches have
made powerful one-pot multi-component reaction (MCR) strate-
gies as one of the most efficient and cost-effective tools for com-
binatorial synthesis in drug discovery processes.1–7 Furthermore,
owing to their green credentials, ionic liquids (ILs) have attracted
considerable interest as environmentally benign reaction media8–11
catalysts,11–13 and reagents,14,15 and are easy to recycle.14,15
utilized for exploiting chemical diversity and generating a drug-like
library to screen for lead candidates.
Recently, we have reported a convenient synthetic approach for
2-amino-1,3-thiazines from chalcones using a task specific ionic
liquid (TSIL).23o Keeping the synthetic and pharmacological im-
portance of –NH2 and –SH groups in mind, we turned our attention
to utilize such type of a,b-unsaturated carbonyl systems, which can
1,3-Thiazines and their derivatives possess remarkable bio-
logical activities such as antibacterial, antitumour, insecticidal and
fungicidal.16–18 These are also known as anti-radiation agents and
used as radiation-sickness drugs.19 Furthermore, the antibiotic ac-
tivity of cephalosporins is due to the presence of 1,3-thiazine nu-
cleus.20 As regards chemical viewpoint, 1,3-thiazines are important
synthetic intermediates in organic syntheses.21 Transformation of
1,3-thiazines into 6-alkyluracils and dihydropyrimidines has also
been reported.16b,22 Owing to their chemical and biological interest,
syntheses of various 1,3-thiazine derivatives have been repor-
ted.16,23 Literature records only few reports on the synthesis of
introduce one additional –NH2 and –SH groups into 2-amino-1,3-
thiazines, which are the target molecules of the present in-
vestigation. For this purpose, we utilized a,b-unsaturated carbonyl
building blocks 1 and 2 (Fig. 1) resulting from Knoevenagel
condensation of aromatic aldehydes with masked and activated
amino and mercapto acids, 2-phenyl-1,3-oxazol-5-one and 2-
methyl-2-phenyl-1,3-oxathiolan-5-one, which lead to the desired
functionalized 1,3-thiazines and are the cornerstones in the present
successful synthetic strategy. The present work is an outcome of
Ar
Ar
2-amino-1,3-thiazines starting from
a,b-unsaturated carbonyl
N
S
Me
Ph
systems.16b,17 To date, no effort has been made for the synthesis of
O
Ph
O
O
O
2
1
* Corresponding author. Tel.: þ91 5322500652; fax: þ91 5322460533.
E-mail address: ldsyadav@hotmail.com (L.D.S. Yadav).
Figure 1. Designed
amino and mercapto functionalities.
a,b-unsaturated carbonyl building blocks 1 and 2 for introducing
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.12.050

L.D.S. Yadav et al. / Tetrahedron 65 (2009) 1306–1315
1307
O
H
R
Ar
S
H
O
Ar
Ar
5
N
NH
6
N
N
δ
O
O
Ph
S
O
O
1
Ph
H
N
Ph
N
O
3
δ
Br
H
N
N
Br
Ar
Ar
H
H
H
O
NHR
NH
Ar
Ar
S
H
S
NHR
NH
H
H2N
H
H
S
H3O
N
Ph
N
N
H
δ
O
δ
Ph
N
NHR
N
NHR
O
O
O
O
Ph
O
H
9
7
10
N
N
Br
7,9,10
Ar
R
7,9,10
Ar
R
a
b
c
d
Ph
H
e
f
4-MeOC6H4
H
Ph
H
Ph
4-MeOC6H4
Ph
H
4-ClC6H4
4-ClC6H4
4-Me2NC6H4
4-Me2NC6H4
g
h
Ph
Ph
Scheme 1. Tentative mechanism for the formation of 2,5-diamino-1,3-thiazines 7 and 10.
our interest in devising new stereoselective heterocyclization
processes.24
In order to achieve our goal expeditiously, we relied upon
significant advantages of the IL, [Bmim]Br as a green catalyst.
Interestingly, the strategy involves the initial treatment of 2-phe-
acid 4, respectively, in acetonitrile at rt. In the next step, the isolated
1 (Ar¼Ph) and 2 (Ar¼Ph) were treated separately with thiourea 6
(R¼H) in the presence of [Bmim]Br under similar reaction condi-
tions to afford the target 1,3-thiazines 7a and 8a, respectively, in
excellent yields (90% of 7a, 86% of 8a) and higher trans diaster-
eoselectivity (96% of 7a, 97% of 8a).
nyl-1,3-oxazol-5-one
3 or 2-methyl-2-phenyl-1,3-oxathiolan-5-
one 4 with aromatic aldehydes 5 followed by reaction of in situ
generated arylidenes 1 and 2 with thioureas 6 to afford 2,5-dia-
mino-/2-amino-5-mercapto-1,3-thiazin-4-ones 7 and 8 in excellent
yields (81–93%) with 94–99% trans diastereoselectivity (Schemes 1
and 2).
In order to make the synthesis of compounds 7 and 8 more
convenient, we turned our attention to perform the above two
steps in a one-pot procedure. Thus, we investigated the optimiza-
tion of reaction conditions in regard with catalyst and solvent both.
Herein, benzaldehyde 5 (Ar¼Ph) and thiourea 6 (R¼H) along with 3
and 4 were chosen as the model substrates for the synthesis of
representative compounds 7a and 8a, respectively, and the reaction
was performed at rt (Table 1). Several imidazolium-based ILs were
tested by varying their alkyl substituents as well as the counter
anion were tested and [Bmim]Br was found to be the most effective
catalyst (Table 1, entry 4) in the present synthetic protocol. On in-
creasing the cation size in the IL no appreciable effect on yields and
diastereoselectivities was observed (Table 1, entries 4, 8 and 9). The
2. Results and discussion
In our initial attempt, 4-benzylidene-2-phenyloxazol-5-one 1
(Ar¼Ph; mp 165–166 ꢀC) and 4-benzylidene-2-methyl-2-phenyl-
1,3-oxathiolan-5-one 2 (Ar¼Ph; mp 187–189 ꢀC) were obtained in
59–64% yield by [Bmim]Br-promoted Knoevenagel condensation of
benzaldehyde with masked amino acid 3 and masked mercapto
O
H
R
Ar
S
H
O
Ar
Ar
5
S
NH
6
S
S
Ph
Me
δ
Ph
Me
O
O
O
O
2
N
Ph
N
O
Me
4
δ
Br
H
N
N
Br
Ar
Ar
H
NHR
NH
S
H
H
Ar
S
S
NHR
H
H
HS
H
S
S
NH
δ
Ph
Me
-PhCOMe
O
Ph
O
11
O
N
NHR
O
O
Me
δ
H
8
N
N
Br
8,11
Ar
R
H
Ar
R
8,11
a
b
c
d
Ph
Ph
4-ClC6H4
4-ClC6H4
H
4-MeOC6H4
4-MeOC6H4
4-Me2NC6H4
4-Me2NC6H4
e
f
Ph
H
Ph
H
g
h
Ph
Ph
Scheme 2. Tentative mechanism for the formation of 2-amino-5-mercapto-1,3-thiazines 8.

1308
L.D.S. Yadav et al. / Tetrahedron 65 (2009) 1306–1315
Table 1
instead of rt, led to decreased diastereoselectivity without any
appreciable effect on the yield. Next, in order to investigate the
substrate scope of the reaction, a variety of aromatic aldehydes 5
and thioureas 6 were used employing the present optimized re-
action conditions and the yields and diastereoselectivities were
found to be consistently good (Table 2), the highest yield being 92%
of 7 (Table 2, entry 9) and 93% of 8 (Table 2, entry 17) and the best
trans diastereoselectivity being 98% of 7 (Table 2, entries 9 and 10)
and 99% of 8 (Table 2, entry 17).
Optimization of reaction conditions for the formation of representative compounds
7a and 8aa
O
O
N
O
H
H
O
Ph
S
Ph
S
Ph
H
Ph
H
H
3
catalyst
5
or
Ph
N
+
or
HS
O
solvent
H
O
rt, 10 h
S
N
NH2
N
NH2
O
S
Me
Ph
H2N
NH2
O
7a
8a
4
6
The present optimized synthesis is accomplished by stirring
a mixture of 2-phenyl-1,3-oxazol-5-one 3 or 2-methyl-2-phenyl-
1,3-oxathiolan-5-one 4, aromatic aldehyde 5 and [Bmim]Br in
CH3CN at rt for 3–5 h followed by addition of thiourea 6 and further
stirring of the reaction mixture at rt for 6–9 h. Isolation and puri-
fication by recrystallization afforded hitherto unknown 1,3-thi-
azines 7 and 8 in 81–93% yield with 94–99% diastereoselectivity
(Table 2) in favour of the trans isomer as determined by 1H NMR
spectroscopy. In trans isomers 7 and 8, 5-H and 6-H are axial as
indicated by their coupling constant (J5,6¼9.1–9.3 Hz, Jtrans; the cis
coupling constant J5,6¼3.9 Hz). The absence of any measurable NOE
between 5-H and 6-H also supports the trans stereochemistry of
compounds 7–10. The diastereomeric ratios in the crude isolates
were checked by 1H NMR spectroscopy to note any inadvertent
alteration of these ratios during subsequent purification. The crude
isolates of 7 and 8 were found to be a diastereomeric mixture
containing 92–96% and 93–98% of the trans isomer, respectively.
The transition states leading to the formation of Michael adducts 9
and 11 adopt the most stable anti-configuration about the ensuing
C–C bond. Thus, 9 and 11 are formed with high anti-diaster-
eoselectivity, which is also retained in 7 and 8 as the chiral carbons
of 9 and 11 incorporated in products 7 and 8 are not involved in any
bond breaking/formation (Schemes 1 and 2).
Entry
1
Cat. (mol %)
Solvent Yieldb (%)
cis/transc
7a 8a
7a
8a
THF
31
27
23:77 27:73
N
Br
N
N
N
(20)
(20)
(20)
N
Br
2
MeOH
CH2Cl2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
63
41
90
72
77
65
90
90
73
59
38
86
78
75
69
86
86
79
35:65 38:62
45:55 49:51
04:96 03:97
41:59 43:57
21:79 15:85
20:80 27:73
04:96 03:97
04:96 03:97
12:88 09:91
04:96 03:97
N
Br
3
N
Br
N
N
4
(20)
(20)
N
5
PF6
N
N
N
6
(20)
(20)
Cl
The formation of 7 and 8 maybe tentativelyrationalized byattack
of more nucleophilic sulfur atom of thiourea 6 at the b-carbon of
N
7
compounds 1 and 2 leading to the formation of adducts 9 and 11,
which undergo intramolecular nucleophilic attack of relativelymore
nucleophilic unsubstituted nitrogen of thiourea 6 at the carbonyl
carbon(C-5) of oxazol-5-one and oxathiolan-5-onenuclei toyield 7and
8, respectively (Schemes 1 and 2). Compounds 7 on debenzoylation
afforded compounds 10 in 88–94% yields and high diastereo-
selectivities (Scheme 1). Furthermore, the acetophenone, which was
used to activate the mercaptoacetic acid to act as a masked mercapto
acid, was removed during the course of reaction without requiring
any protection–deprotection step yielding compounds 8 (Scheme
2). These conclusions are based on the observation that the repre-
sentative intermediate compounds 9a, 9c, 9g and 11a,11c,11g could
be isolated in 41–52% yields, respectively, and that these could be
converted into the corresponding annulated products 7a, 7c, 7g and
8a, 8c, 8g in quantitative yield (Table 2).
BF4
N
N
8
Br
(20)
(20)
(15)
(25)
N
N
9
Br
N
N
N
10
11
Br
N
CH3CN
CH3CN
90
00
86
00
Br
12
d
d
d
a
3. Conclusion
For the experimental procedure, see Sections 4.3 and 4.6.
Yield of isolated and purified products.
b
c
As determined by 1H NMR spectroscopy f the crude products.
In summary, we have developed an original and practical method
for the synthesis of potentially pharmaceutically important 2,5-
diamino-/2-amino-5-mercapto-1,3-thiazin-4H-ones from readily
available simple substrates. This one-pot diastereoselective syn-
thesis is operationally simple, high yielding, and is performed at rt
using the ionic liquid [Bmim]Br as an environmentally benign cat-
alyst, and may find application in organic synthesis.
optimum catalyst loading for [Bmim]Br was found to be 20 mol %.
When the amount of the catalyst decreased to 15 mol % from
20 mol % relative to substrates, the yield and diastereoselectivity of
products 7a and 8a reduced (Table 1, entry 10), but the use 25 mol %
of the catalyst showed the same yield and diastereoselectivity
(Table 1, entry 11) as shown in entry 4 of Table 1. However, the
reaction did not occur without using the catalyst (Table 1, entry 12).
Optimization of the solvents for the synthesis of 7a and 8a was also
undertaken and it was found that amongst THF, CH2Cl2, MeOH and
CH3CN (Table 1, entries 1–4), the best solvent in terms of yield and
diastereoselectivity was CH3CN (Table 1, entry 4). It was noted that
a higher reaction temperature, for example, in a refluxing solvent
4. Experimental
4.1. General
Melting points were determined by open glass capillary method
and are uncorrected. IR spectra in KBr were recorded on a Perkin–

L.D.S. Yadav et al. / Tetrahedron 65 (2009) 1306–1315
1309
Table 2
Ionic liquid [Bmim]Br-catalyzed synthesis of products 7–11
H
H
O
Ar
S
Ar
S
[Bmim]Br
O
or
O
+
H
S
O
H
N
S
CH3CN
or
NHR
Ph
N
+
Me
Ph
HS
O
O
Ar
H2N
NHR
H
H
rt, 9-14 h
81-93%
Ph
N
NHR
N
7
O
O
3
4
5
6
8
Entry
Masked acids 3 and 4
Products 7–11
Timea (h)
Yieldb,c (%)
cis/transd
04:96
H
S
NH2
1
3
5
41
H
N
NH
O
Ph
O
9a
Cl
H
H
N
S
NH2
2
3
4
48
05:95
NH
O
Ph
9c
O
NMe2
H
O
S
NH2
NH
H
3
3
6
52
03:97
N
O
Ph
Ph
9g
H
O
H
4
5
3
3
10
11
90
91
04:96
03:97
S
N
H
N
O
NH2
7a
H
O
H
S
Ph
N
H
N
O
NHPh
Cl
7b
H
O
6
3
9
88
05:95
H
S
Ph
7c
N
H
N
O
NH2
Cl
H
O
7
3
11
83
06:94
H
S
Ph
7d
N
H
N
O
NHPh
OMe
H
O
8
3
12
85
05:95
H
S
Ph
7e
N
H
N
O
NH2
(continued on next page)

1310
L.D.S. Yadav et al. / Tetrahedron 65 (2009) 1306–1315
Table 2 (continued )
Entry
Masked acids 3 and 4
Products 7–11
Timea (h)
Yieldb,c (%)
cis/transd
02:98
OMe
H
O
9
3
11
11
14
92
H
S
Ph
7f
N
H
N
O
NHPh
NMe2
H
O
10
11
3
89
02:98
H
S
Ph
N
H
N
O
NH2
7g
NMe2
H
O
3
81
06:94
H
S
Ph
N
H
N
O
NHPh
7h
H
H
S
S
NH2
NH
12
4
5
44
03:97
Ph
Me
O
O
11a
Cl
H
S
NH2
NH
H
13
4
4
47
01:99
S
Ph
O
O
Me
11c
NMe2
H
S
NH2
NH
H
14
4
6
51
02:98
S
Ph
O
O
Me
11g
H
H
15
16
4
4
10
12
86
92
03:97
03:97
S
HS
O
N
NH2
8a
H
H
HS
S
O
N
NHPh
Cl
8b
H
17
4
9
93
01:99
H
HS
S
O
NH2
N
8c

L.D.S. Yadav et al. / Tetrahedron 65 (2009) 1306–1315
1311
Table 2 (continued )
Entry
Masked acids 3 and 4
Products 7–11
Cl
Timea (h)
Yieldb,c (%)
cis/transd
H
18
19
4
12
13
88
04:96
03:97
H
HS
O
S
NHPh
OMe
N
8d
H
4
4
4
4
85
93
91
88
H
HS
O
S
NH2
N
8e
OMe
H
20
21
13
13
14
02:98
02:98
04:96
H
HS
O
S
NHPh
NMe2
8f
N
H
H
H
HS
O
S
NH2
N
8g
NMe2
22
H
HS
S
O
NHPh
N
8h
a
Stirring time at room temperature.
Yield of isolated and purified products.
b
c
All compounds gave C, H and N analyses ꢃ0.37% and satisfactory spectral (IR, 1H NMR, 13C NMR and EIMS) data.
d
As determined by 1H NMR spectroscopy of the crude products.
Elmer 993 IR spectrophotometer, 1H NMR spectra were recorded on
a Bruker WM-40 C (400 MHz) FT spectrometer in DMSO-d6þD2O
using TMS as internal reference. 13C NMR spectra were recorded on
the same instrument at 100 MHz in DMSO-d6 and TMS was used as
internal reference. Mass spectra were recorded on a JEOL D-300
mass spectrometer. Elemental analyses were carried out in a Cole-
man automatic carbon, hydrogen and nitrogen analyzer. All
chemicals used were reagent grade and were used as received
without further purification. Silica gel-G was used for TLC.
4.2.1. Compound 1 (Ar¼Ph)
Yellowish solid (0.30 g, 59%), mp 134–136 ꢀC. IR (KBr) nmax 3011,
1778, 1601, 1579, 1448 cmꢂ1. 1H NMR (DMSO-d6þD2O/TMS)
d: 7.14–
7.60 (m, 11Harom). 13C NMR (DMSO-d6/TMS)
d: 110.5, 126.2, 126.8,
127.5, 128.3, 129.0, 130.7,131.5, 132.2, 133.9, 161.5, 173.5. EIMS (m/z):
249 (Mþ). Anal. Calcd for C16H11NO2: C, 77.10; H, 4.45; N, 5.62.
Found: C, 77.41; H, 4.67; N, 5.48.
4.2.2. Compound 2 (Ar¼Ph)
Yellowish solid (0.36 g, 64%), mp 112–114 ꢀC. IR (KBr) nmax 1775,
4.2. 4-Benzylidene-2-phenyloxazol-5-one 1 (Ar[Ph)
and 4-benzylidene-2-methyl-2-phenyl-1,3-oxathiolan-
5-one 2 (Ar[Ph): procedure
1605, 1585,1452 cmꢂ1. 1H NMR (DMSO-d6þD2O/TMS)
d: 2.03 (s, 3H,
Me), 7.03–7.48 (m, 11Harom). 13C NMR (DMSO-d6/TMS)
d: 17.6, 35.3,
126.4,127.1,127.8,128.4,129.0,129.8,130.5,131.2,131.9,132.6,173.3.
EIMS (m/z): 282 (Mþ). Anal. Calcd for C17H14O2S: C, 72.31; H, 5.00.
Found: C, 72.01; H, 5.33.
A mixture of 2-phenyl-1,3-oxazol-5-one 3 (2.0 mmol) or 2-
methyl-2-phenyl-1,3-oxathiolan-5-one
4 (2.0 mmol), benzalde-
hyde (2.0 mmol) and [Bmim]Br (0.4 mmol) in 8 mL of CH3CN was
stirred at rt for 5 h. After completion of the reaction as indicated by
TLC, 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 recrystallized from
ethanol to afford an analytically pure sample of 1 or 2, respectively,
in 59–64% yield. After isolation of the product, the remaining
aqueous layer containing the ionic liquid was washed with ether
(2ꢁ10 mL) to remove any organic impurity and filtered. The filtrate
was extracted with dichloromethane (3ꢁ10 mL), dried over MgSO4
and evaporated under reduced pressure to afford [Bmim]Br, which
was used in subsequent runs without further purification.
4.3. 2-Amino-5-benzamido-1,3-thiazin-4H-ones 7: general
procedure
A mixture of 2-phenyl-1,3-oxazol-5-one 3 (2.0 mmol), aldehyde
5 (2.0 mmol) and [Bmim]Br (0.4 mmol) in 10 mL of CH3CN was
stirred at rt for 3–5 h. Then, thiourea 6 (2.0 mmol) was added to the
mixture and stirring was continued for further 6–9 h at rt. After
completion of the reaction as indicated by TLC, 20 mL of water was
added, and the product was extracted with EtOAc (3ꢁ20 mL). The
combined organic layers were dried over anhydrous Na2SO4 and
evaporated under vacuum to afford the crude product, which was
recrystallized from ethanol to afford a diastereomeric mixture

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L.D.S. Yadav et al. / Tetrahedron 65 (2009) 1306–1315
(>93:<07; in the crude products the ratio was >91:<09 as de-
termined by 1H NMR spectroscopy). The product on second re-
crystallization from ethanol furnished an analytically pure sample
of a single diastereomer 7 (Table 2). On the basis of comparison of
J values with the literature values,23i,25–30 the trans stereochemistry
was assigned to 6, as the coupling constant (J5,6¼9.1 Hz) of the
major trans isomer was higher than that for the minor cis di-
astereomer (J5,6¼3.9 Hz). The ionic liquid [Bmim]Br was recovered
by following the same procedure as described in Section 4.2.
162.2, 172.5, 173.9. EIMS (m/z): 431 (Mþ). Anal. Calcd for
C24H21N3O3S: C, 66.80; H, 4.91; N, 9.74. Found: C, 67.08; H, 4.73; N,
9.92.
4.3.7. Compound 7g
Yellowish solid (0.66 g, 89%), mp 178–180 ꢀC. IR (KBr) nmax 3341,
3315, 3008, 1743, 1682, 1601, 1581, 1455, 1313 cmꢂ1 1H NMR
.
(DMSO-d6þD2O/TMS)
J5H,6H¼9.1 Hz, 6-H), 5.61 (d, 1H, J5H,6H¼9.1 Hz, 5-H), 6.98–7.86 (m,
9Harom). 13C NMR (DMSO-d6/TMS)
: 35.0, 42.5, 43.4, 65.5, 127.0,
d
:
2.95 (s, 6H, 2ꢁMe), 5.02 (d, 1H,
d
4.3.1. Compound 7a
127.7, 128.4, 129.0, 129.7, 131.3, 132.1, 133.2, 162.1, 172.1, 173.5. EIMS
(m/z): 368 (Mþ). Anal. Calcd for C19H20N4O2S: C, 61.94; H, 5.47; N,
15.21. Found: C, 61.59; H, 5.62; N, 14.93.
Yellowish solid (0.59 g, 90%), mp 211–213 ꢀC. IR (KBr) nmax 3343,
3308, 3013,1745,1685,1601,1582,1452,1315 cmꢂ1. 1H NMR (DMSO-
d6þD2O/TMS)
d
: 5.06 (d, 1H, J5H,6H¼9.1 Hz, 6-H), 5.61 (d, 1H,
J5H,6H¼9.1 Hz, 5-H), 7.22–7.81 (m,10Harom).13C NMR (DMSO-d6/TMS)
4.3.8. Compound 7h
d
: 35.2, 65.7,127.1,127.8,128.5,129.2,130.5,132.0,132.9,133.5, 162.8,
Yellowish solid (0.76 g, 86%), mp 141–143 ꢀC. IR (KBr) nmax 3340,
172.2, 174.5. EIMS (m/z): 325 (Mþ). Anal. Calcd for C17H15N3O2S: C,
3308, 3011,1742,1681,1604,1580,1450,1312 cmꢂ1.1H NMR (DMSO-
62.75; H, 4.65; N, 12.91. Found: C, 62.38; H, 4.91; N, 12.76.
d6þD2O/TMS) : 2.97 (s, 6H, 2ꢁMe), 5.01 (d, 1H, J5H,6H¼9.1 Hz, 6-H),
d
5.67 (d, 1H, J5H,6H¼9.1 Hz, 5-H), 7.01–7.91 (m, 14Harom). 13C NMR
4.3.2. Compound 7b
(DMSO-d6/TMS) d: 35.1, 42.7, 43.5, 65.5, 126.6, 127.2, 127.9, 128.6,
Yellowish solid (0.73 g, 91%), mp 110–112 ꢀC. IR (KBr) nmax 3341,
129.4, 130.0, 131.7, 131.4, 132.0, 132.7, 133.4, 134.1, 162.0, 172.3, 173.5.
EIMS (m/z): 444 (Mþ). Anal. Calcd for C25H24N4O2S: C, 67.54; H, 5.44;
N, 12.60. Found: C, 67.88; H, 5.18; N, 12.49.
3307, 3011, 1744, 1687, 1600, 1580, 1455, 1315 cmꢂ1 1H NMR
.
(DMSO-d6þD2O/TMS) : 5.08 (d,1H, J5H,6H¼9.1 Hz, 6-H), 5.60 (d,1H,
d
J5H,6H¼9.1 Hz, 5-H), 7.10–7.98 (m, 15Harom). 13C NMR (DMSO-d6/
TMS)
d
: 35.3, 65.9, 126.5, 127.1, 127.8, 128.4, 129.0, 129.7, 130.3, 131.0,
4.4. Isolation of Michael adducts 9a, 9c and 9g and their
conversion into the corresponding annulated products
7a, 7c and 7g
131.6, 132.3, 133.0, 133.8, 162.1, 172.4, 173.9. EIMS (m/z): 401 (Mþ).
Anal. Calcd for C23H19N3O2S: C, 68.81; H, 4.77; N, 10.47. Found: C,
69.05; H, 4.51; N, 10.72.
The procedure followed was the same as described above for the
synthesis of 7 (Section 4.3) except that the time of stirring in this
case after addition of thiourea 6 was 1–2 h instead of 6–9 h for 7.
Adducts 9 were purified by silica gel column chromatography
(hexane/EtOAc, 3:1) to obtain an analytically pure sample of 9 in
41–52% yield. The crude product was found to be a diastereomeric
mixture containing 92–96% of the anti isomer as determined by 1H
NMR spectroscopy. Adducts 9 were assigned the anti stereochem-
istry as their 1H NMR spectra exhibited higher values of coupling
constant, JNCH,SCH¼9.3 Hz, than that of syn diastereomer,
JNCH,SCH¼4.1 Hz.23i,25–30 A mixture of the intermediate compound
9a, 9c or 9g (2.0 mmol) and [Bmim]Br (0.4 mmol) in 8 mL of CH3CN
was stirred at rt for 4–7 h to give the corresponding products 7a, 7c
or 7e quantitatively. These were isolated and purified in the same
way as described above in Section 4.3.
4.3.3. Compound 7c
Yellowish solid (0.63 g, 88%), mp 174–176 ꢀC. IR (KBr) nmax 3348,
3310, 3009, 1747, 1686, 1603, 1583, 1459, 1316 cmꢂ1 1H NMR
.
(DMSO-d6þD2O/TMS)
J5H,6H¼9.1 Hz, 5-H), 7.05–7.51 (m, 7Harom), 7.66–7.89 (m, 2Harom).
13C NMR (DMSO-d6/TMS)
: 35.4, 65.8, 126.4, 127.7, 128.6, 129.3,
130.4, 131.5, 132.8, 133.4, 162.5, 172.0, 173.5. EIMS (m/z): 359, 361
(M, Mþ2). Anal. Calcd for C17H14ClN3O2S: C, 56.74; H, 3.92; N, 11.68.
Found: C, 55.48; H, 4.17; N, 11.91.
d
: 5.09 (d,1H, J5H,6H¼9.1 Hz, 6-H), 5.68 (d,1H,
d
4.3.4. Compound 7d
Yellowish solid (0.72 g, 83%), mp 104–105 ꢀC. IR (KBr) nmax 3338,
3316, 3017, 1748, 1688, 1605, 1586, 1460, 1318 cmꢂ1 1H NMR
.
(DMSO-d6þD2O/TMS)
J5H,6H¼9.1 Hz, 5-H), 7.08–7.49 (m, 12Harom), 7.62–7.91 (m, 2Harom).
13C NMR (DMSO-d6/TMS)
: 35.7, 66.1, 126.3, 127.0, 127.7, 128.3,
129.1, 129.8, 130.4, 131.0, 131.7, 132.4, 133.0, 133.7, 162.3, 171.9, 173.3.
EIMS (m/z): 435, 437 (M, Mþ2). Anal. Calcd for C23H18ClN3O2S: C,
63.37; H, 4.16; N, 9.64. Found: C, 63.69; H, 4.37; N, 9.55.
d: 5.07 (d,1H, J5H,6H¼9.1 Hz, 6-H), 5.65 (d,1H,
d
4.4.1. Compound 9a
Yellowish solid (0.27 g, 41%), mp 189–191 ꢀC. IR (KBr) nmax 3342,
3147, 3050, 1775, 1605, 1583, 1450 cmꢂ1. 1H NMR (DMSO-d6þD2O/
TMS)
d
:
6.65 (d, 1H, JNCH,SCH¼9.3 Hz, SCH), 6.78 (d, 1H,
JNCH,SCH¼9.3 Hz, NCH), 7.05–7.79 (m, 10Harom). 13C NMR (DMSO-d6/
4.3.5. Compound 7e
TMS) d: 60.3, 63.7, 126.1, 126.8, 127.5, 128.3, 129.0, 129.9, 130.7, 132.5,
Yellowish solid (0.60 g, 85%), mp 126–128 ꢀC. IR (KBr) nmax 3341,
159.2,161.9,173.2. EIMS(m/z):325(Mþ). Anal. CalcdforC17H15N3O2S:
3310, 3011, 1743, 1682, 1601, 1581, 1455,1313 cmꢂ1. 1H NMR (DMSO-
C, 62.75; H, 4.65; N, 12.91. Found: C, 62.38; H, 4.81; N, 12.69.
d6þD2O/TMS) : 3.76 (s, 3H, OMe), 5.03 (d, 1H, J5H,6H¼9.1 Hz, 6-H),
d
5.60 (d, 1H, J5H,6H¼9.1 Hz, 5-H), 7.03–7.90 (m, 9Harom). 13C NMR
4.4.2. Compound 9c
(DMSO-d6/TMS)
d
: 35.6, 56.1, 66.0, 126.7, 127.3, 128.2, 129.0, 129.9,
Yellowish solid (0.34 g, 48%), mp 155–157 ꢀC. IR (KBr) nmax 3340,
3139, 3039, 1779, 1598, 1585, 1455 cmꢂ1. 1H NMR (DMSO-d6þD2O/
131.4, 132.4, 133.5, 162.6, 172.2, 174.1. EIMS (m/z): 355 (Mþ). Anal.
Calcd for C18H17N3O3S: C, 60.83; H, 4.82; N, 11.82. Found: C, 60.59;
H, 4.61; N, 11.91.
TMS)
d
:
6.63 (d, 1H, JNCH,SCH¼9.3 Hz, SCH), 6.80 (d, 1H,
JNCH,SCH¼9.3 Hz, NCH), 7.11–7.59 (m, 7Harom), 7.63–7.85 (m, 2Harom).
13C NMR (DMSO-d6/TMS)
d: 60.7, 64.2, 126.3, 127.2, 128.3, 129.2,
4.3.6. Compound 7f
130.1,131.7, 132.8, 133.7,159.5,162.4,172.9. EIMS (m/z): 359, 361 (M,
Mþ2). Anal. Calcd for C17H14ClN3O2S: C, 56.74; H, 3.92; N, 11.68.
Found: C, 56.49; H, 3.78; N, 11.89.
Yellowish solid (0.80 g, 92%), mp 86–87 ꢀC. IR (KBr) nmax 3343,
3310, 3013, 1744, 1683, 1599, 1582, 1457, 1314 cmꢂ1 1H NMR
.
(DMSO-d6þD2O/TMS)
J5H,6H¼9.1 Hz, 6-H), 5.66 (d, 1H, J5H,6H¼9.1 Hz, 5-H), 7.07–7.88 (m,
14Harom). 13C NMR (DMSO-d6/TMS)
: 35.8, 56.4, 65.9, 126.3, 127.0,
127.5, 128.2, 129.2, 129.8, 130.5, 131.2, 131.9, 132.5, 133.1, 133.9,
d: 3.73 (s, 3H, OMe), 5.09 (d, 1H,
4.4.3. Compound 9g
d
Yellowish solid (0.38 g, 52%), mp 161–163 ꢀC. IR (KBr) nmax 3340,
3143, 3031, 1771, 1608, 1579, 1458 cmꢂ1. 1H NMR (DMSO-d6þD2O/

L.D.S. Yadav et al. / Tetrahedron 65 (2009) 1306–1315
1313
TMS)
d
: 2.53 (s, 6H, 2ꢁMe), 6.61 (d, 1H, JNCH,SCH¼9.3 Hz, SCH), 6.74
(DMSO-d6/TMS)
d
: 35.7, 56.1, 66.7, 126.2, 127.1, 127.9, 128.5, 129.4,
(d, 1H, JNCH,SCH¼9.3 Hz, NCH), 7.19–7.75 (m, 9Harom). 13C NMR
130.2, 131.1, 132.8, 163.1, 173.3. EIMS (m/z): 327 (Mþ). Anal. Calcd for
C17H17N3O2S: C, 62.36; H, 5.23; N, 12.83. Found: C, 62.62; H, 5.08; N,
12.71.
(DMSO-d6/TMS) d: 42.5, 43.8, 60.5, 63.8, 126.2, 127.1, 127.9, 128.3,
129.5, 131.2, 131.9, 132.7, 159.0, 161.8, 173.3. EIMS (m/z): 368 (Mþ).
Anal. Calcd for C19H20N4O2S: C, 61.94; H, 5.47; N, 15.21. Found: C,
62.31; H, 5.59; N, 15.03.
4.5.7. Compound 10g
Yellowish solid (0.49 g, 92%), mp 161–163 ꢀC. IR (KBr) nmax 3339,
4.5. 2,5-Diamino-1,3-thiazin-4H-ones 10: general procedure
3309, 3042, 1752, 1591, 1585, 1452, 1309 cmꢂ1 1H NMR (DMSO-
.
d6þD2O/TMS) : 2.92 (s, 6H, 2ꢁMe), 4.92 (d,1H, J5H,6H¼9.3 Hz, 6-H),
d
Compound 7 (2.0 mmol) was refluxed in H2SO4/H2O (15 mL, 4:3,
v/v) for 45 min in an oil bath. The reaction mixture was cooled, the
desired product 10 was precipitated by adding concentrated
NH4OH (specific gravity 0.88) under ice cooling and recrystallized
from ethanol to obtain an analytically pure sample of 10.
5.47 (d, 1H, J5H,6H¼9.3 Hz, 5-H), 7.01–7.63 (m, 4Harom). 13C NMR
(DMSO-d6/TMS) d: 35.4, 42.1, 43.4, 65.5, 126.3, 128.5, 130.6, 133.2,
162.8, 172.9. EIMS (m/z): 264 (Mþ). Anal. Calcd for C12H16N4OS: C,
54.52; H, 6.10; N, 21.19. Found: C, 54.28; H, 5.89; N, 21.37.
4.5.8. Compound 10h
4.5.1. Compound 10a
Yellowish solid (0.61 g, 88%), mp 117–119 ꢀC. IR (KBr) nmax 3342,
Yellowish solid (0.40 g, 90%), mp 143–145 ꢀC. IR (KBr) nmax 3347,
3317, 3049, 1755, 1606, 1576, 1456, 1314 cmꢂ1 1H NMR (DMSO-
.
3311, 3050, 1751, 1605, 1583, 1451, 1310 cmꢂ1
.
1H NMR (DMSO-
d6þD2O/TMS) : 2.96 (s, 6H, 2ꢁMe), 4.90 (d,1H, J5H,6H¼9.3 Hz, 6-H),
d
d6þD2O/TMS)
d
: 4.91 (d, 1H, J5H,6H¼9.3 Hz, 6-H), 5.49 (d, 1H,
5.54 (d, 1H, J5H,6H¼9.3 Hz, 5-H), 6.95–7.88 (m, 9Harom). 13C NMR
J5H,6H¼9.3 Hz, 5-H), 7.01–7.51 (m, 5Harom). 13C NMR (DMSO-d6/
(DMSO-d6/TMS) d: 35.1, 42.4, 43.3, 65.1, 126.1, 127.8, 128.5, 129.9,
TMS)
d: 35.5, 65.8, 126.5, 128.2, 130.5, 132.9, 162.7, 173.5. EIMS
130.5, 131.3, 132.5, 133.3, 163.2, 173.1. EIMS (m/z): 340 (Mþ). Anal.
Calcd for C18H20N4OS: C, 63.50; H, 5.92; N,16.46. Found: C, 63.27; H,
6.13; N, 16.22.
(m/z): 221 (Mþ). Anal. Calcd for C10H11N3OS: C, 54.28; H, 5.01; N,
18.99. Found: C, 54.61; H, 5.19; N, 18.83.
4.5.2. Compound 10b
4.6. 2-Amino-5-mercapto-1,3-thiazin-4H-ones 8: general
procedure
Yellowish solid (0.52 g, 88%), mp 121–123 ꢀC. IR (KBr) nmax 3341,
3308, 3051, 1745, 1601, 1581, 1456, 1312 cmꢂ1 1H NMR (DMSO-
.
d6þD2O/TMS)
d
: 4.94 (d, 1H, J5H,6H¼9.3 Hz, 6-H), 5.51 (d, 1H,
The procedure followed was the same as described above for the
synthesis of 7 except that the starting material in this case was 2-
methyl-2-phenyl-1,3-oxathiolan-5-one 4 instead of 2-phenyl-1,3-
oxazol-5-one 3. The crude product 8 obtained was recrystallized
from ethanol to afford a diastereomeric mixture (>95:<05; in the
crude products the ratio was >92:<08 as determined by 1H NMR
spectroscopy). To obtain analytically pure sample of a single di-
astereomer 8 (Table 2) and to assign the stereochemistry, the same
procedure was adopted as described for 7 (Section 4.3). The ionic
liquid [Bmim]Br was recovered by following the same procedure as
described in Section 4.2.
J5H,6H¼9.3 Hz, 5-H), 7.11–7.65 (m, 10Harom). 13C NMR (DMSO-d6/
TMS) d: 35.1, 65.2,126.2,127.8,128.5,129.7,130.9, 131.5,132.2, 133.6,
162.5, 172.8. EIMS (m/z): 297 (Mþ). Anal. Calcd for C16H15N3OS: C,
64.62; H, 5.08; N, 14.13. Found: C, 64.29; H, 5.17; N, 13.99.
4.5.3. Compound 10c
Yellowish solid (0.47 g, 93%), mp 151–153 ꢀC. IR (KBr) nmax 3338,
3313, 3048, 1750, 1608, 1586, 1449, 1311 cmꢂ1 1H NMR (DMSO-
.
d6þD2O/TMS)
d: 4.90 (d, 1H, J5H,6H¼9.3 Hz, 6-H), 5.53 (d, 1H,
J5H,6H¼9.3 Hz, 5-H), 7.01–7.31 (m, 2Harom), 7.61–7.75 (m, 2Harom).13
C
NMR (DMSO-d6/TMS) d: 35.5, 65.5, 126.5, 128.2, 130.8, 132.9, 163.0,
173.1. EIMS (m/z): 255, 257 (M, Mþ2). Anal. Calcd for C10H10ClN3OS:
4.6.1. Compound 8a
C, 46.97; H, 3.94; N, 16.43. Found: C, 46.73; H, 3.65; N, 16.61.
Yellowish solid (0.41 g, 86%), mp 187–189 ꢀC. IR (KBr) nmax 3351,
3052, 1759, 2565, 1598, 1580, 1455, 1315 cmꢂ1 1H NMR (DMSO-
.
4.5.4. Compound 10d
d6þD2O/TMS)
d
: 5.13 (d, 1H, J5H,6H¼9.2 Hz, 6-H), 5.75 (d, 1H,
Yellowish solid (0.62 g, 89%), mp 88–89 ꢀC. IR (KBr) nmax 3344,
J5H,6H¼9.2 Hz, 5-H), 7.41–7.85 (m, 5Harom). 13C NMR (DMSO-d6/
3312, 3055, 1748, 1599, 1581, 1457, 1308 cmꢂ1
.
1H NMR (DMSO-
TMS) d: 35.1, 65.6, 127.2, 129.1, 130.9, 132.1, 163.1, 172.9. EIMS (m/z):
d6þD2O/TMS)
J5H,6H¼9.3 Hz, 5-H), 7.02–7.55 (m, 7Harom), 7.62–7.79 (m, 2Harom).
13C NMR (DMSO-d6/TMS)
: 35.8, 65.1, 126.0, 127.8, 128.6, 130.9,
d: 4.93 (d, 1H, J5H,6H¼9.3 Hz, 6-H), 5.48 (d, 1H,
238 (Mþ). Anal. Calcd for C10H10N2OS2: C, 50.40; H, 4.23; N, 11.75.
Found: C, 50.03; H, 4.11; N, 11.99.
d
131.5, 132.2, 133.0, 133.8, 162.8, 172.6. EIMS (m/z): 331, 333 (M,
Mþ2). Anal. Calcd for C16H14ClN3OS: C, 57.91; H, 4.25; N, 10.68.
Found: C, 58.28; H, 4.07; N, 10.91.
4.6.2. Compound 8b
Yellowish solid (0.58 g, 92%), mp 134–136 ꢀC. IR (KBr) nmax 3348,
3055, 1755, 2559, 1603, 1583, 1449, 1308 cmꢂ1 1H NMR (DMSO-
.
d6þD2O/TMS)
d
: 5.11 (d, 1H, J5H,6H¼9.2 Hz, 6-H), 5.72 (d, 1H,
4.5.5. Compound 10e
J5H,6H¼9.2 Hz, 5-H), 7.33–7.95 (m, 10Harom). 13C NMR (DMSO-d6/
Yellowish solid (0.47 g, 94%), mp 103–105 ꢀC. IR (KBr) nmax 3340,
TMS) d: 35.7, 66.4, 126.5, 127.2, 128.1, 128.8, 129.8, 130.4, 131.7, 133.2,
3310, 3045, 1753, 1598, 1579, 1450, 1313 cmꢂ1
.
1H NMR (DMSO-
162.8, 173.1. EIMS (m/z): 314 (Mþ). Anal. Calcd for C16H14N2OS2: C,
d6þD2O/TMS)
d
: 3.78 (s, 3H, OMe), 4.88 (d, 1H, J5H,6H¼9.3 Hz, 6-H),
61.12; H, 4.49; N, 8.91. Found: C, 60.88; H, 4.77; N, 8.72.
5.49 (d, 1H, J5H,6H¼9.3 Hz, 5-H), 7.12–7.65 (m, 4Harom). 13C NMR
(DMSO-d6/TMS)
d
: 35.3, 56.3, 66.4, 126.8, 128.9, 131.5, 132.8, 162.7,
4.6.3. Compound 8c
173.0. EIMS (m/z): 251 (Mþ). Anal. Calcd for C11H13N3O2S: C, 52.57;
Yellowish solid (0.51 g, 93%), mp 85–87 ꢀC. IR (KBr) nmax 3355,
H, 5.21; N, 16.72. Found: C, 52.88; H, 5.47; N, 16.59.
3051, 1761, 2561, 1607, 1579, 1452, 1311 cmꢂ1 1H NMR (DMSO-
.
d6þD2O/TMS)
J5H,6H¼9.2 Hz, 5-H), 7.05–7.39 (m, 2Harom), 7.59–7.66 (m, 2Harom).
13C NMR (DMSO-d6/TMS)
: 35.8, 66.1, 127.5, 128.8, 131.2, 133.3,
162.5, 172.9. EIMS (m/z): 272, 274 (M, Mþ2). Anal. Calcd for
C10H9ClN2OS2: C, 44.03; H, 3.33; N, 10.27. Found: C, 44.27; H, 3.19;
N, 10.15.
d
: 5.18 (d, 1H, J5H,6H¼9.2 Hz, 6-H), 5.79 (d, 1H,
4.5.6. Compound 10f
Yellowish solid (0.59 g, 90%), mp 95–96 ꢀC. IR (KBr) nmax 3345,
d
3315, 3047, 1758, 1602, 1580, 1453, 1316 cmꢂ1
.
1H NMR (DMSO-
d6þD2O/TMS) : 3.72 (s, 3H, OMe), 4.89 (d, 1H, J5H,6H¼9.3 Hz, 6-H),
d
5.50 (d, 1H, J5H,6H¼9.3 Hz, 5-H), 7.09–7.83 (m, 9Harom). 13C NMR

1314
L.D.S. Yadav et al. / Tetrahedron 65 (2009) 1306–1315
4.6.4. Compound 8d
acyclicSCH), 6.77 (d, 1H, JcyclicSCH,acyclicSCH¼9.2 Hz, cyclicSCH), 7.21–
7.83 (m, 10Harom). 13C NMR (DMSO-d6/TMS)
: 17.3, 34.8, 65.1, 68.8,
126.1, 126.7, 127.5, 128.6, 129.7, 130.5, 131.1, 132.9, 162.1, 173.5. EIMS
(m/z): 358 (Mþ). Anal. Calcd for C18H18N2O2S2: C, 60.31; H, 5.06; N,
7.81. Found: C, 62.57; H, 5.23; N, 7.65.
Yellowish solid (0.61 g, 88%), mp 193–195 ꢀC. IR (KBr) nmax 3350,
d
3051, 1762, 2555, 1599, 1585, 1457, 1317 cmꢂ1
d6þD2O/TMS) : 5.12 (d, 1H, J5H,6H¼9.2 Hz, 6-H), 5.72 (d, 1H,
J5H,6H¼9.2 Hz, 5-H), 7.11–7.58 (m, 7Harom), 7.65–7.85 (m, 2Harom).
13C NMR (DMSO-d6/TMS)
: 35.5, 66.2, 126.3, 127.1, 127.8, 128.5,
.
1H NMR (DMSO-
d
d
129.3, 130.1, 130.9, 132.5, 163.2, 173.3. EIMS (m/z): 348, 350 (M,
Mþ2). Anal. Calcd for C16H13ClN2OS2: C, 55.08; H, 3.76; N, 8.03.
Found: C, 54.73; H, 3.89; N, 8.18.
4.7.2. Compound 11c
Yellowish solid (0.37 g, 47%), mp 123–125 ꢀC. IR (KBr) nmax 3341,
3133, 3035, 1780, 1606, 1578, 1451 cmꢂ1. 1H NMR (DMSO-d6þD2O/
TMS)
d
: 2.29 (s, 3H, Me), 6.59 (d, 1H, JcyclicSCH,acyclicSCH¼9.2 Hz,
4.6.5. Compound 8e
acyclicSCH), 6.73 (d, 1H, JcyclicSCH,acyclicSCH¼9.2 Hz, cyclicSCH), 7.08–
Yellowish solid (0.46 g, 85%), mp 99–101 ꢀC. IR (KBr) nmax 3347,
7.49 (m, 7Harom), 7.58–7.71 (m, 2Harom). 13C NMR (DMSO-d6/TMS)
d:
3048, 1758, 2558, 1601, 1582, 1453, 1310 cmꢂ1
.
1H NMR (DMSO-
17.5, 34.7, 65.5, 69.5, 126.5, 127.3, 128.0, 128.8, 129.5, 130.2, 131.9,
133.7, 162.8, 172.9. EIMS (m/z): 392, 394 (M, Mþ2). Anal. Calcd for
C18H17ClN2O2S2: C, 55.02; H, 4.36; N, 7.13. Found: C, 55.29; H, 4.17;
N, 7.30.
d6þD2O/TMS) : 3.75 (s, 3H, OMe), 5.09 (d, 1H, J5H,6H¼9.2 Hz, 6-H),
d
5.71 (d, 1H, J5H,6H¼9.2 Hz, 5-H), 7.08–7.50 (m, 4Harom). 13C NMR
(DMSO-d6/TMS) d: 35.2, 56.7, 66.8, 127.2, 129.5, 130.9, 133.1, 162.8,
172.8. EIMS (m/z): 268 (Mþ). Anal. Calcd for C11H12N2O2S2: C, 49.23;
H, 4.51; N, 10.44. Found: C, 49.51; H, 4.33; N, 10.57.
4.7.3. Compound 11g
Yellowish solid (0.41 g, 51%), mp 140–142 ꢀC. IR (KBr) nmax
4.6.6. Compound 8f
3340, 3132, 3031, 1778, 1596, 1575, 1449 cmꢂ1 1H NMR (DMSO-
.
Yellowish solid (0.64 g, 93%), mp 123–125 ꢀC. IR (KBr) nmax 3351,
d6þD2O/TMS)
JcyclicSCH,acyclicSCH¼9.2 Hz, acyclicSCH), 6.78 (d, 1H, JcyclicSCH,acyclicSCH
9.2 Hz, cyclicSCH), 7.21–7.89 (m, 9Harom). 13C NMR (DMSO-d6/TMS)
d
: 2.23 (s, 3H, Me), 2.55 (s, 6H, 2ꢁMe), 6.61 (d, 1H,
3053, 1752, 2561, 1605, 1577, 1448, 1316 cmꢂ1
.
1H NMR (DMSO-
¼
d6þD2O/TMS) : 3.77 (s, 3H, OMe), 5.15 (d, 1H, J5H,6H¼9.2 Hz, 6-H),
d
5.76 (d, 1H, J5H,6H¼9.2 Hz, 5-H), 7.12–7.91 (m, 9Harom). 13C NMR
d: 17.4, 34.5, 42.1, 43.9, 65.3, 69.6, 126.3, 127.0, 127.8, 128.5, 129.3,
(DMSO-d6/TMS)
d
: 36.1, 56.8, 66.5, 126.5, 127.2, 127.9, 128.8, 129.5,
130.1, 131.0, 132.3, 161.9, 172.6. EIMS (m/z): 401 (Mþ). Anal. Calcd for
C20H23N3O2S2: C, 59.82; H, 5.77; N, 10.46. Found: C, 59.51; H, 5.53;
N, 10.21.
130.3, 131.5, 132.9, 163.2, 172.6. EIMS (m/z): 344 (Mþ). Anal. Calcd
for C17H16N2O2S2: C, 59.28; H, 4.68; N, 8.13. Found: C, 59.63; H, 4.79;
N, 7.98.
Acknowledgements
4.6.7. Compound 8g
Yellowish solid (0.51 g, 91%), mp 111–113 ꢀC. IR (KBr) nmax 3352,
We sincerely thank SAIF, Punjab University, Chandigarh, for
providing microanalyses and spectra.
3046, 1753, 2560, 1601, 1581, 1458, 1309 cmꢂ1 1H NMR (DMSO-
.
d6þD2O/TMS) : 3.01 (s, 6H, 2ꢁMe), 5.11 (d, 1H, J5H,6H¼9.2 Hz, 6-H),
d
5.73 (d, 1H, J5H,6H¼9.2 Hz, 5-H), 7.05–7.81 (m, 4Harom). 13C NMR
References and notes
(DMSO-d6/TMS) d: 35.9, 42.8, 43.9, 66.5, 127.5, 128.9, 131.5, 133.4,
163.1, 173.3. EIMS (m/z): 281 (Mþ). Anal. Calcd for C12H15N3OS2: C,
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Yellowish solid (0.63 g, 88%), mp 161–163 ꢀC. IR (KBr) nmax 3350,
3049, 1765, 2563, 1606, 1583, 1455, 1312 cmꢂ1 1H NMR (DMSO-
.
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d
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Yellowish solid (0.32 g, 44%), mp 108–110 ꢀC. IR (KBr) nmax 3339,
3135, 3038, 1781, 1602, 1587, 1457 cmꢂ1. 1H NMR (DMSO-d6þD2O/
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