A novel four-component tandem protocol for the stereoselective synthesis of highly functionalised thiazoles

Article abstract of DOI:10.1016/j.tet.2007.07.040

The reaction of bis(aroylmethyl) sulfides with aromatic aldehydes and ammonium acetate in 1:2:1 molar ratio under solvent-free microwave irradiation afforded predominantly a series of thiazoles, viz., 1-aryl-2-[5(Z)-5-arylmethylidene-2,4-diaryl-2,5-dihydr

Full text of DOI:10.1016/j.tet.2007.07.040

Tetrahedron 63 (2007) 10054–10058
A novel four-component tandem protocol for the stereoselective
synthesis of highly functionalised thiazoles
a
a
b
Subbiah Renuga,a, Michael Gnanadeebam, Beer Mohamed Vinosha and Subbu Perumal
*
aDepartment of Chemistry, Fatima College, Madurai 625018, India
bSchool of Chemistry, Madurai Kamaraj University, Madurai 625021, India
Received 24 April 2007; revised 28 June 2007; accepted 12 July 2007
Available online 19 July 2007
Abstract—The reaction of bis(aroylmethyl) sulfides with aromatic aldehydes and ammonium acetate in 1:2:1 molar ratio under solvent-free
microwave irradiation afforded predominantly a series of thiazoles, viz., 1-aryl-2-[5(Z)-5-arylmethylidene-2,4-diaryl-2,5-dihydrothiazol-2-
yl]ethanones stereoselectively. This reaction presumably occurs via a Knoevenagel condensation–Michael addition–cyclocondensation–
ring opening–ring closing Michael addition sequence. The intermediacy of (Z,Z)-2,20-thiobis(1,3-diarylprop-2-en-1-ones) in the above
transformation is demonstrated by their conversion to the thiazoles upon reaction with ammonium acetate under solvent-free microwave
irradiation.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
In the present work, the reaction of bis(aroylmethyl) sulfides
with aromatic aldehydes and ammonium acetate has been ef-
fected under solvent-free microwave irradiation, as it is not
uncommon to get different products from reactions under
solvent-free microwave irradiation and in solution under
conventional heating. This is ascribable to the fact that
under solvent-free conditions the transition state, being sur-
rounded by only reactant molecules in place of solvent, is
bound to have an environment with different polarity than
that in solution. This, in turn, can enable quite different reac-
tions under solventless condition and in solution. Microwave
irradiation also, in general, favours reactions involving more
polar transition states and often leads to different product se-
lectivities than the thermal reactions.6–10 Further, reactions
under microwave irradiation often proceed more rapidly
than the conventional thermal reactions with diminished de-
composition of the reactants and/or products thus minimis-
ing the waste and enhancing the yield.
Thiazines are known for their important biological activities
such as anti-HIV,1 anti-fungal, anthelmintic, anti-inflamma-
tory2 and anti-psoriatic.3 Previously, diastereomeric 2,6-di-
aroyl-3,5-diaryltetrahydro-1,4-thiazines (3 and 4) have
been obtained, respectively, from the reaction of aromatic
aldehydes and ammonium acetate with bis(aroylmethyl) sul-
fides 1,4 and from the reaction of (Z,Z)-2,20-thiobis(1,3-
diarylprop-2-en-1-ones) 2 with ammonia5 in moderate
yields (Scheme 1).
COAr
Ar'CHO
Ar
Ar
S
Ar'
HN
S
NH4OAc
EtOH, 60-80 °C
O
O
Ar'
COAr
3
1
Ar'
O
Aqueous
ammonia
S
COAr
S
It is pertinent to note that, in accord with the above observa-
tions, in the present investigation, the reaction of bis(aroyl-
methyl) sulfides 1 with aromatic aldehydes and ammonium
acetate in 1:2:1 molar ratio under solvent-free microwave ir-
radiation, afforded predominantly tetrasubstituted thiazoles
via tandem reactions instead of the 1,4-thiazines previously
reported in solution.4,5 The results of these investigations
are presented in this paper. Incidentally, tandem reactions
fall under green synthetic protocols as they lead to conver-
gent, elegant, efficient and eco-friendly construction of
complex molecules without isolating and purifying the inter-
mediates thus minimising waste, labour and cost.11,12
Ar
Ar'
HN
COAr
DMF, r.t.
O
Ar
Ar'
4
Ar'
2
Scheme 1. Formation of diastereomeric tetrahydro-1,4-thiazines.
Keywords: Tandem reactions; Bis(aroylmethyl) sulfides; Microwave irradi-
ation; Solvent-free; Thiazole.
* Corresponding author. Tel.: +91 452 2668016; fax: +91 452 2668437;
e-mail: s.renuga@gmail.com
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.07.040

S. Renuga et al. / Tetrahedron 63 (2007) 10054–10058
Table 1. Yields and melting points of thiazolesa 5
10055
Moreover, this investigation, affording hitherto unknown
Yieldsa (%)
Mp (ꢀC)
thiazoles serendipitously, assumes importance since the
thiazoles display numerous biological activities such as
anti-inflammatory,13 anti-tumour,14 anti-fungal15 and anti-
microbial.16
5
Ar
Ar0
Method 1b Method 2c
a
b
c
d
e
f
C6H5
C6H5
C6H5
C6H5
70
73
62
68
71
80
76
79
84
82
81
85
176—178
165—167
166—168
150—152
158—160
136—138
138—140
p-Cl–C6H4
o-Cl–C6H4
C6H5
p-Cl–C6H4
p-Cl–C6H4
p-Cl–C6H4
2. Results and discussion
p-Cl–C6H4
p-Me–C6H4 63
p-Me–C6H4 C6H5 66
g
In the present investigation, bis(aroylmethyl) sulfide 1, an
aromatic aldehyde and ammonium acetate were thoroughly
mixed in a borosilicate boiling tube kept partially immersed
in a silica bath, which, in turn, was placed in a microwave
oven (750 W and frequency of 2450 MHz) and irradiated
at power level 4 of a total scale of 6. Completion of the re-
action (TLC) requires 10 min of microwave irradiation in
one stretch without intermittent cooling. This reaction led
to the formation of three products (Scheme 2), which were
obtained in a pure form by column chromatography on silica
gel with ethyl acetate–petroleum ether mixture [2:98 (v/v)]
as eluent.
a
b
c
After purification by column chromatography.
Obtained from the reaction of 1 with ArCHO and NH4OAc.
Obtained from the reaction of 2 with NH4OAc.
HMBC correlation with (i) the methylene protons, and (ii)
the aromatic protons at 7.58 ppm of the p-tolyl ring. The
methyls of the tolyl rings give 1H signals at 2.31 and
2.35 ppm and 13C signals at 21.4and 21.0 ppm. These13C sig-
nalshaveHMBCcorrelationswitharomatichydrogensat7.14
and 7.19 ppm, respectively. The signals at 7.58 and 7.14 ppm,
related by an H,H-COSY correlation, are due to the protons
meta and ortho to the methyl of p-tolyl ring at C-2. The signals
at 7.19 and 7.43 ppm having an H,H-COSY correlation are as-
signed to the protons ortho and meta to the methyl groupin the
other tolyl group. The DEPT spectrum of 5f confirms the pres-
ence of one methylene carbon and one quaternary carbon in
the aliphatic region (C-3).
The major product was identified as a thiazole derivative 5
from elemental analysis and 1H, 13C and 2D NMR spectro-
scopic data. The yields and melting points of 5a–5g are given
in Table 1. Of the two minor products, the one obtained in 7–
10% yields was found to be the already known (Z,Z)-2,20-
thiobis(1,3-diarylprop-2-en-1-ones) 2, while the other
formed in negligible amounts was identified as 2-[(2-oxo-
The imine carbon (C-4) signal at 168.6 ppm has an HMBC
correlation with the singlet at 6.74 ppm assigning it to aryl-
methylidene hydrogen. The latter has a C,H-COSY cor-
relation with the carbon signal at 125.7 ppm, which in
turn correlates with the H signal at 7.43 ppm (HMBC)
due to the Hs of the tolyl ring, suggesting that the second
p-tolyl ring is present in the arylmethylidene function. The
signals due to the other protons and carbons of 5f are also
assigned similarly. The important HMBC correlations and
2-phenylethyl)sulfanyl]-1,3-diphenylprop-2-en-1-one
(Scheme 2).
6
The elucidation of the structure of 5 using one- and two-
dimensional NMR spectroscopic data is discussed with 5f as
an example. The 1H doublets at 4.44 and 3.85 ppm
(J¼17.1 Hz) due to the diastereotopic methylene hydrogens
have an HMBC correlation with the carbonyl at 194.8 ppm
disclosing their proximity (Fig. 1). That the 13C signal at
92.6 ppm is due to C-2 of the thiazole is evident from its
the H and 13C chemical shifts of 5f are given in Figures
1 and 2, respectively.
1
Ar'
Ar'
O
Ar'
O
Ar
Ar
S
1
S
S
Ar
S
Ar
O
O
Ar
MW
+
+
Ar
O
N
2 Ar'CHO
NH4OAc
O
Ar
Ar'
Ar
No solvent
O
Ar'
5
2
6
major
7-10%
(negligible)
NH4OAc
2
5
MW, No solvent
2 & 5
Ar
Ar'
C6H5
C6H5
a
b
c
d
e
f
C6H5
p-Cl-C6H4
o-Cl-C6H4
C6H5
C6H5
p-Cl-C6H4
p-Cl-C6H4
p-Cl-C6H4
p-Me-C6H4
p-Cl-C6H4
p-Me-C6H4
C6H5
g
Scheme 2. Formation of thiazoles 5 by tandem reactions.

10056
S. Renuga et al. / Tetrahedron 63 (2007) 10054–10058
CH3
Cl
H
H
H
H
O
S
H
CH2
H
N
H
H
CH3
Cl
H
Figure 1. HMBC correlations of 5f.
The 1H and 13C spectroscopic features of 5a–5e and 5g are
also similar to 5f, except for the substituent effects. The
structure for 5b in solid state deduced from X-ray crystallo-
graphic studies is similar to 5f (Fig. 3).
2.31
(21.4)
7.38
H
CH3
Cl
7.19
7.43
H
7.86
H
H
O
S
(194.8)
3.85, 4.44
(125.7)
(52.3)
CH2
(92.6)
6.74 H
(168.6)
N
H
7.58
H
CH3
2.35
Cl
Figure 3. X-ray crystal structure of 5b.
7.52
H
(21.0)
H
7.45
7.14
Figure 2. 1H and 13C chemical shifts of 5f.
employed for the reaction of bis(aroylmethyl) sulfide 1
(Scheme 2). The yields of 5 (76–85%) obtained in the trans-
formation of 2 to 5 are better than those obtained from 1 (62–
73%) (Table 1).
The mechanism (Scheme 3) envisages an initial Knoevena-
gel condensation of bis(aroylmethyl) sulfide with two mole-
cules of aromatic aldehyde to give 2. This is presumably
followed by Michael addition of ammonia with concomitant
cyclocondensation to give 7. Base catalysed ring opening of
7 to 8 and ring closing Michael addition of 8 to 3 complete
the tandem sequence. Presumably, the ring opening of 7 to 8
is driven by the stability of the fully conjugated azatrienone
system 8. The formation of minor products 2 and 6 is also in
consonance with the mechanism.
3. Conclusions
The present work describes the predominant formation of
highly functionalised thiazoles under solvent-free micro-
wave irradiation presumably via a tandem sequence of reac-
tions. This study discloses the complementary nature of the
present protocol to the solution state chemistry, which
demonstrates that the product selectivity can be tuned by
employing appropriate reaction conditions. Further investi-
gations on the utility of these thiazoles as synthons in the
construction of novel heterocycles are being currently
explored in our group.
The involvement of (Z,Z)-2,20-thiobis(1,3-diarylprop-2-en-
1-ones) 2 as an intermediate in this reaction is evident
from the reaction of an equimolar mixture of (Z,Z)-2,20-thio-
bis(1,3-diarylprop-2-en-1-ones) 2 and ammonium acetate
furnishing 5 as the major product under the conditions
Ar'
O
Ar'
O
Knoevenagel
S
Michael
addition
S
Ar
Ar
Ar
condensation
Ar
S
2 Ar'CHO
NH4OAc
O
O
O
Ar
Ar'
Ar'
O
Ar
H2N
NH3
1
2
Cyclocondensation
Ar'
Ar'
O
Ar'
O
S-
S
Ring closing
Michael addition
Base-catalysed
ring opening
Ar
S
Ar
Ar
Ar
N
Ar'
O
Ar'
N
Ar
N
H
Ar
Ar'
7
:NH3
5
8
Scheme 3. Mechanism for the formation of thiazoles 5.

S. Renuga et al. / Tetrahedron 63 (2007) 10054–10058
10057
4. Experimental section
4.1. General methods
143.3, 169.6, 195.9. Anal. Calcd for C30H23NOS:
C, 80.87; H, 5.20; N, 3.14. Obsd: C, 81.01; H, 5.16; N,
3.10%.
The melting points are uncorrected. A domestic microwave
oven (IFB, model-electron of 750 W capacity and micro-
wave frequency of 2450 MHz) was employed for microwave
irradiation. NMR spectra were recorded at 20 ꢀC on a Bruker
4.2.2. 2-[(5Z)-5-(p-Chlorobenzylidene)-2-(p-chloro-
phenyl)-2,5-dihydro-4-phenylthiazol-2-yl]-1-phenyl-
ethanone (5b). Obtained as a colourless solid (0.750 g,
73% in method 1 and 0.392 g, 76% in method 2),
1
1
mp¼165–167 ꢀC; IR (KBr) n 1690, 1592, 1487 cmꢁ1; H
AMX 300 instrument operating at 300 MHz for H and at
75 MHz for 13C. Solutions (in CDCl3) were approximately
0.05 M and chemical shifts were referenced internally to
TMS in all cases and expressed in d scale (ppm). Two-
dimensional NMR measurements H,H-COSY, C,H-COSY
and HMBC have also been measured using the above instru-
ment. Standard Bruker software (UXNMR) was used
throughout. The single crystal X-ray data for 5b were col-
lected on an Enraf-Nonius MACH 3 four-circle diffracto-
NMR (300 MHz, CDCl3) dH 3.87 (1H, d, J¼17.7 Hz),
4.55 (1H, d, J¼17.7 Hz), 6.78 (1H, s), 7.27–7.99 (18H,
m); 13C NMR (75 MHz, CDCl3) dC 52.4, 92.6, 124.5,
128.1, 128.3, 128.5 (7), 128.5 (9), 128.6, 128.7, 129.0,
130.0, 130.1, 133.1, 133.5, 133.6, 134.4, 136.4, 140.5,
141.6, 169.6, 195.8. Anal. Calcd for C30H21Cl2NOS: C,
70.04; H, 4.11; N, 2.72. Obsd: C, 69.97; H, 4.08; N,
2.76%.
˚
meter (Mo Ka radiation, l¼0.71073 A). Elemental
analyses were performed on a Perkin–Elmer 2400 Series II
Elemental CHNS Analyser.
4.2.3. 2-[(5Z)-5-(o-Chlorobenzylidene)-2-(o-chloro-
phenyl)-2,5-dihydro-4-phenylthiazol-2-yl]-1-phenyl-
ethanone (5c). Obtained as a colourless solid (0.639 g, 62%
in method 1 and 0.408 g, 79% in method 2), mp¼166–
4.2. Synthesis of 1-aryl-2-[5(Z)-5-arylmethylidene-2,4-
diaryl-2,5-dihydrothiazol-2-yl]ethanones—general
procedure
168 ꢀC; IR (KBr) n 1693, 1612, 1463 cmꢁ1 1H NMR
;
(300 MHz, CDCl3) dH 4.17 (1H, d, J¼15.3 Hz), 4.43 (1H,
d, J¼15.3 Hz), 7.15–7.94 (19H, m); 13C NMR (75 MHz,
CDCl3) dC 48.1, 91.5, 121.6, 126.9, 127.0, 128.1, 128.3
(9), 128.4 (4), 128.6, 128.9 (6), 129.0 (4), 129.2, 129.5,
130.1, 130.9, 131.6, 132.8, 133.3, 134.2, 134.3, 137.8,
141.4, 142.6, 170.8, 195.9. Anal. Calcd for C30H21Cl2NOS:
C, 70.04; H, 4.11; N, 2.72. Obsd: C, 70.08; H, 4.14; N,
2.68%.
Method 1: by the reaction of bis(aroylmethyl) sulfide, aro-
matic aldehyde and ammonium acetate. A mixture of
bis(benzoylmethyl) sulfide (0.54 g, 2 mmol), benzaldehyde
(0.4 mL, 4 mmol) and ammonium acetate (0.154 g,
2 mmol) was taken in a glass mortar and ground to a homo-
geneous paste with a pestle. This paste was then transferred
to a borosilicate boiling tube, kept in a silica bath and placed
in a domestic microwave oven at power level 4 for 10 min.
The TLC analysis of the reaction mixture shows that the
reaction goes to completion in 10 min affording three prod-
ucts. These products were separated by column chromato-
graphy using ethyl acetate–petroleum ether [2:98 (v/v)]
mixture.
4.2.4. 2-[(5Z)-5-Benzylidene-4-(p-chlorophenyl)-2,5-di-
hydro-2-phenylthiazol-2-yl]-1-(p-chlorophenyl)ethanone
(5d). Isolated as a colourless solid (0.700 g, 68% in method 1
and 0.433 g, 84% in method 2), mp¼150–152 ꢀC; IR (KBr)
1
n 1676, 1588, 1488 cmꢁ1; H NMR (300 MHz, CDCl3) dH
3.89 (1H, d, J¼17.1 Hz), 4.47 (1H, d, J¼17.1 Hz), 6.80
(1H, s), 7.25–7.89 (18H, m); 13C NMR (75 MHz, CDCl3)
dC 52.2, 92.8, 125.7, 126.8, 127.8, 128.2 (7), 128.3 (2),
128.6, 128.8, 128.9, 129.6, 130.5, 131.8, 135.1, 135.7,
136.2, 139.7 (6), 139.7 (9), 143.2, 168.8, 194.7. Anal. Calcd
for C30H21Cl2NOS: C, 70.04; H, 4.11; N, 2.72. Obsd: C,
69.99; H, 4.09; N, 2.76%.
Among the two minor products, the one obtained in 7–
10% yields was the known compound (Z,Z)-2,20-thiobis-
(1,3-diphenylprop-2-en-1-one) 2 and the other obtained in
negligible amount was identified as 2-[(2-oxo-2-phenyl-
ethyl)sulfanyl]-1,3-diphenylprop-2-en-1-one 6. The thiazole
derivative was obtained as the major product, which was
recrystallised from chloroform–alcohol mixture.
4.2.5. 2-[(5Z)-5-(p-Chlorobenzylidene)-2,4-bis(p-chloro-
phenyl)-2,5-dihydrothiazol-2-yl]-1-(p-chlorophenyl)-
ethanone (5e). Obtained as a colourless solid (0.830 g, 71%
in method 1 and 0.480 g, 82% in method 2), mp¼158–
Method 2: by the reaction of (Z,Z)-2,20-thiobis(1,3-diaryl-
prop-2-en-1-ones) and ammonium acetate. The procedure
is the same as the one described in method 1 except that in
this method, the reactants are a mixture of (Z,Z)-2,20-thiobis-
(1,3-diarylprop-2-en-1-ones)17 (1 mmol) and ammonium
acetate (1 mmol).
160 ꢀC; IR (KBr) n 1680, 1576, 1478 cmꢁ1 1H NMR
;
(300 MHz, CDCl3) dH 3.83 (1H, d, J¼17.5 Hz), 4.44 (1H,
d, J¼17.5 Hz), 6.73 (1H, s), 7.26–7.86 (16H, m); 13C
NMR (75 MHz, CDCl3) dC 52.4, 92.6, 124.6, 128.4 (0),
128.4 (3), 128.8, 128.9, 129.0, 129.5, 130.0, 130.5, 133.8,
133.9, 134.1, 134.8, 140.1, 141.5, 168.8, 194.5. Anal. Calcd
for C30H19Cl4NOS: C, 61.77; H, 3.28; N, 2.40. Obsd: C,
61.62; H, 3.26; N, 2.43%.
4.2.1. 2-[(5Z)-5-Benzylidene-2,5-dihydro-2,4-diphenylthi-
azol-2-yl]-1-phenylethanone (5a). Obtained as a colour-
less solid (0.624 g, 70% in method 1 and 0.358 g, 80% in
method 2), mp¼176–178 ꢀC; IR (KBr) n 1695, 1586,
1
1485 cmꢁ1; H NMR (300 MHz, CDCl3) dH 3.90 (1H, d,
4.2.6. 2-[(5Z)-5-(p-Methylbenzylidene)-4-(p-chloro-
phenyl)-2,5-dihydro-2-(p-methylphenyl)thiazol-2-yl]-1-
(p-chlorophenyl)ethanone (5f). Obtained as a colourless
solid (0.684 g, 63% in method 1 and 0.441 g, 81% in method
J¼17.4 Hz), 4.57 (1H, d, J¼17.4 Hz), 6.83 (1H, s), 7.24–
7.94 (20H, m); 13C NMR (75 MHz, CDCl3) dC 52.2, 92.8,
125.6, 127.0, 127.7, 128.0, 128.1, 128.2, 128.5, 128.6,
128.9, 129.2, 129.9, 133.3, 133.5, 136.0, 136.7, 140.2,

10058
S. Renuga et al. / Tetrahedron 63 (2007) 10054–10058
2), mp¼136–138 ꢀC; IR (KBr) n 1675, 1575, 1483 cmꢁ1; 1H
NMR (300 MHz, CDCl3) dH 2.31 (3H, s), 2.35 (3H, s), 3.85
(1H, d, J¼17.1 Hz), 4.44 (1H, d, J¼17.1 Hz), 6.74 (1H, s),
7.14–7.87 (16H, m); 13C NMR (75 MHz, CDCl3) dC 21.0,
21.4, 52.3, 92.6, 125.7, 126.7, 128.7, 128.8, 129.0, 129.3,
129.6, 130.6, 132.0, 133.0, 135.2, 136.1, 137.6, 138.5,
138.8, 139.7, 140.3, 168.6, 194.8. Anal. Calcd for
C32H25Cl2NOS: C, 70.84; H, 4.64; N, 2.58. Obsd: C,
70.75; H, 4.67; N, 2.55%.
Supplementary data
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2007.07.040.
References and notes
1. Arranz, M. E.; Diaz, J. A.; Ingate, S. T.; Witvrouw, M.;
Pannecouque, C.; Balzarini, J.; De Clercq, E.; Vega, S.
Bioorg. Med. Chem. 1999, 7, 2811.
4.2.7. 2-[(5Z)-5-Benzylidene-2,5-dihydro-4-(p-methyl-
phenyl)-2-phenylthiazol-2-yl]-1-(p-methylphenyl)etha-
none (5g). Obtained as a colourless solid (0.626 g, 66% in
method 1 and 0.404 g, 85% in method 2), mp¼138–
2. Srivastava, S. K.; Yadav, R.; Srivastav, S. D. Indian J. Chem.,
Sect. B 2004, 43, 399.
3. Moriyama, H.; Tsukida, T.; Inoue, Y.; Yokota, K.; Yoshino, K.;
Kondo, H.; Miura, N.; Nishimura, S. J. Med. Chem. 2004, 47,
1930.
140 ꢀC; IR (KBr) n 1678, 1585, 1473 cmꢁ1 1H NMR
;
(300 MHz, CDCl3) dH 2.39 (3H, s), 2.44 (3H, s), 3.86 (1H,
d, J¼17.4 Hz), 4.56 (1H, d, J¼17.4 Hz), 6.86 (1H, s),
7.14–7.85 (18H, m); 13C NMR (75 MHz, CDCl3) dC 21.4,
21.6, 52.2, 92.7, 125.3, 127.0, 127.5, 127.9, 128.1, 128.3,
128.5, 128.8, 129.1, 129.2, 130.6, 134.3, 136.1, 140.1,
140.3, 143.4, 144.1, 169.5, 195.7. Anal. Calcd for
C32H27NOS: C, 81.15; H, 5.75; N, 2.96. Obsd: C, 81.05;
H, 5.69; N, 2.98%.
4. Selvaraj, S.; Dhanabalan, A.; Mercypushphalatha, A.;
Arumugam, N. Phosphorus, Sulfur Silicon Relat. Elem. 1991,
63, 295.
5. Selvaraj, S.; Dhanabalan, A. Madurai Kamaraj University,
unpublished results.
6. Regnier, T.; Lavastre, O. Tetrahedron 2006, 62, 155.
ꢀ
7. Quiroga, J.; Cruz, S.; Insuasty, B.; Abonıa, R.; Nogueras, M.;
Cobo, J. Tetrahedron Lett. 2006, 47, 27.
8. Castagnolo, D.; Renzulli, M. L.; Galletti, E.; Corelli, F.; Botta,
M. Tetrahedron: Asymmetry 2005, 16, 2893.
9. Ju, Y.; Varma, R. S. Tetrahedron Lett. 2005, 46, 6011.
10. Kabalka, G. W.; Mereddy, A. R. Tetrahedron Lett. 2005, 46,
6315.
4.3. X-ray crystallographic determination
of compound 5b
Data were collected at room temperature on an Enraf-
Nonius MACH 3 four-circle diffractometer (Mo Ka
11. (a) Posner, G. H. Chem. Rev. 1986, 86, 831; (b) Tietze, L. F.;
Beifuss, U. Angew. Chem., Int. Ed. Engl. 1993, 32, 131; (c)
Bunce, R. A. Tetrahedron 1995, 48, 13103; (d) Ho, T.-L.
Tandem Organic Reactions; Wiley Interscience: New York,
NY, 1992; (e) Tietze, L. F.; Brasche, C.; Gericke, K. M.
Domino Reactions in Organic Synthesis; Wiley-VCH:
Weinheim, 2006.
12. (a) Gnanadeepam, M.; Selvaraj, S.; Perumal, S.; Renuga, S.
Tetrahedron 2002, 58, 2227; (b) Srinivasan, M.; Perumal, S.
Tetrahedron 2006, 62, 7726; (c) Alex Raja, V. P.; Perumal,
S. Tetrahedron 2006, 62, 4892; (d) Savitha Devi, N.;
Perumal, S. Tetrahedron 2006, 62, 5931; (e) Kamal Nasar,
M.; Ranjith Kumar, R.; Perumal, S. Tetrahedron Lett. 2007,
48, 2155; (f) Karthikeyan, S. V.; Perumal, S. Tetrahedron
Lett. 2007, 48, 2261.
˚
radiation, l¼0.71073 A) for compound 5b. The data col-
lection, integration and data reduction for 5b were per-
formed using CAD-4 EXPRESS18 and XCAD419
programs and an empirical absorption correction was ap-
plied using j scan method.20 The unit cell parameters
were determined by a least square fitting of 25 randomly
selected strong reflections and an empirical absorption
correction was applied using the azimuthal scan method.
The structures were solved by direct methods (SHELXS
97)21 and subsequent Fourier synthesis and refined by
full matrix least squares on SHELX 9722 for all non-
hydrogen atoms of 5b. All hydrogen atoms were placed
in calculated positions.
4.3.1. Compound 5b. C30H21Cl2NOS, M¼514.44, triclinic,
13. Kumar, A.; Rajput, C. S.; Bhati, S. K. Bioorg. Med. Chem.
2007, 15, 3089.
˚
˚
space group P-1, a¼10.355(6) A, b¼10.5240(11) A,
3
˚
˚
c¼13.6390(12) A, V¼1293.1(8) A , Z¼2, F(000)¼532,
m¼0.355 mmꢁ1, Dc¼1.321 Mg mꢁ3. The reflections col-
lected were 5365 of which 4540 were unique
[R(int)¼0.0121]; 3372 reflections I>2s(I), R1¼0.0499 and
wR2¼0.1277 for 3372 [I>2s(I)] and R1¼0.0753
and wR2¼0.1419 for all (4540) intensity data. Goodness
of fit¼1.040, residual electron density in the final
´
ꢁ
´
´
14. Popsavin, M.; Spaic, S.; Svircev, M.; Kojic, V.; Bogdanovic,
G.; Popsavin, V. Bioorg. Med. Chem. Lett. 2006, 16, 5317.
15. Cukurovali, A.; Yilmaz, I.; Gur, S.; Kazaz, C. Eur. J. Med.
Chem. 2006, 41, 201.
16. Vicini, P.; Geronikaki, A.; Anastasia, K.; Incerti, M.; Zani, F.
Bioorg. Med. Chem. 2006, 14, 3859.
17. Gnanadeebam, M.; Renuga, S.; Selvaraj, S.; Perumal, S.
Phosphorus, Sulfur Silicon Relat. Elem. 2004, 179, 203.
18. Enraf-Nonius. CAD-4 EXPRESS Version 5.0; Enraf-Nonius:
Delft, The Netherlands, 1994.
Fourier map was 0.536 and ꢁ0.398 e Aꢁ3. CCDC number
˚
is 643988.
19. Harms, K.; Wocadio, S. XCAD4; University of Marburg:
Marburg, Germany, 1995.
Acknowledgements
20. North, A. C. T.; Philips, D. C.; Mathews, F. S. Acta
Crystallogr., Sect. A 1968, 24, 351.
21. Sheldrick, G. M. Acta Crystallogr., Sect. A 1990, 46, 467.
22. Sheldrick, G. M. SHELX97; University of Gottingen:
Gottingen, Germany, 1997.
S.R. and M.G. thank UGC for the financial support under
Major Research Project and also thank the Correspondent
and the Principal, Fatima College, Madurai-18 for providing
facilities.