Synthesis and spectral characterization of diethyl 2-[aryl(4-aryl-1,2,3- selenadiazol-5-yl)methyl]malonate

Article abstract of DOI:10.1080/10426500490485255

Synthesis and characterization of several diethyl 2-[aryl(4-aryl-1,2,3- selenadiazol-5-yl)methyl]malonates are reported.

Full text of DOI:10.1080/10426500490485255

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Phosphorus, Sulfur, and Silicon
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SYNTHESIS AND SPECTRAL
CHARACTERIZATION OF
DIETHYL 2-[ARYL(4-
ARYL-1,2,3-SELENADIAZOL-5-
YL)METHYL]MALONATE
Sivaperuman Saravanan a & Shanmugam
Muthusubramanian a
a Department of Organic Chemistry, Madurai
Kamaraj University , Madurai, India
Published online: 16 Aug 2010.
To cite this article: Sivaperuman Saravanan & Shanmugam Muthusubramanian (2004)
SYNTHESIS AND SPECTRAL CHARACTERIZATION OF DIETHYL 2-[ARYL(4-ARYL-1,2,3-
SELENADIAZOL-5-YL)METHYL]MALONATE, Phosphorus, Sulfur, and Silicon and the
Related Elements, 179:12, 2411-2421, DOI: 10.1080/10426500490485255
To link to this article: http://dx.doi.org/10.1080/10426500490485255
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Phosphorus, Sulfur, and Silicon, 179:2411–2421, 2004
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Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490485255
SYNTHESIS AND SPECTRAL CHARACTERIZATION
OF DIETHYL 2-[ARYL(4-ARYL-1,2,3-SELENADIAZOL-5-
YL)METHYL]MALONATE
Sivaperuman Saravanan and Shanmugam Muthusubramanian
Department of Organic Chemistry, Madurai Kamaraj
University, Madurai, India
(Received February 25, 2004; accepted April 28, 2004)
Synthesis and characterization of several diethyl 2-[aryl(4-aryl-1,2,3-
selenadiazol-5-yl)methyl]malonates are reported.
Keywords: 1,2,3-Selenadiazoles; 2D NMR; 13C NMR; diethyl 2-[aryl(4-
aryl-1,2,3-selenadiazol-5-yl)methyl]malonate; 1H NMR; selenium
dioxide
INTRODUCTION
Much attention has been paid to the synthesis of various derivatives of
1,2,3-selenadiazoles and 1,2,3-thiadiazoles due to their pharmacologi-
cal properties. Compounds with a 1,2,3-selena/thiadiazole moiety have
been found to exhibit antifungal1,2 and antibacterial3–5 activities. 4,5-
Bis(p-methoxyphenyl)-1,2,3-thiadiazole possesses platelet aggregation
inhibitory activity in humans,6 and some 1,2,3-thiadiazole derivatives
are useful for the therapeutic and prophylactic treatment of viral, bac-
terial, fungal, and parasitic infections in humans and animals.7 This
article reports the synthesis of novel substituted 1,2,3-selenadiazoles
with functional groups, which can be modified to give additional hete-
rocyclic rings.
The authors thank DST, New Delhi for assistance under the IRHPA program for
the NMR facility. S. Saravanan is grateful to CSIR, New Delhi for a Junior Research
Fellowship.
Address correspondence to Shanmugam Muthusubramanian, Department of
Organic Chemistry, Madurai Kamaraj University, Madurai 625021, India. E-mail:
muthumanian2001@yahoo.com
2411

2412
S. Saravanan and S. Muthusubramanian
RESULTS AND DISCUSSION
The adducts, diethyl 2-(3-oxo-1,3-diarylpropyl)malonates (2a–j) have
all been synthesized by reported methods.8 The semicarbazone deriva-
tives of diethyl 2-(3-oxo-1,3-diarylpropyl)malonates 2 (3a–j) were pre-
pared by refluxing aqueous ethanolic solutions of 2, semicarbazide
hydrochloride, and anhydrous sodium acetate. Selenium dioxide oxi-
dation of the semicarbazones in glacial acetic acid gave the desired
selenadiazoles 4 (Scheme 1). The yields of 1,2,3-selenadiazoles from
semicarbazones are moderate (around 50%). However, the treatment
of thionyl chloride with the semicarbazones (3) did not lead to the ex-
pected product but yielded the parent ketones (2) instead of thiadi-
azoles (5). Hydrolysis probably occurred, leading to the formation of
the parent ketone (Scheme 1). Conversion of the parent ketones (2)
to tosylhydrazones and subjecting the latter to thionyl chloride treat-
ment also did not prove to be a useful method of preparing these thia-
diazoles. The compounds 4 have been well characterized by 1H and
13C NMR.
The yields, melting points, and elemental analyses of the semicar-
bazones and the selenadiazoles are given in Table I, while the pro-
ton and carbon NMR of 3 and 4 are presented in Table II. The IR
(KBr) spectrum of semicarbazone 3g exhibits characteristic absorption
bands in the regions 3511.74, 3397.96, 3191.61, 3089.40, 1679.69, and
1565.92 cm−1. The formation of selenadiazoles is evident from the ab-
sence of the characteristic NH and NH2 bands in the IR spectrum of
the selenadiazole 4g. The IR (KBr) spectrum of this selenadiazole shows
absorption bands at 1751.05 cm−1 for carbonyl stretching of the ester
moiety and a weak band at 1513.85 cm−1 for νN=N. The complete assign-
ment of proton and carbon NMR signals for a representative compound
4g (numbered as shown in Scheme 1 for easy reference) is described
here. The proton NMR spectrum of diethyl 2-{[4-(4-chlorophenyl)-1,2,3-
selenadiazol-5-yl](4-methylphenyl)methyl} malonate (4g) exhibits two
triplets, each accounting for three hydrogens at 0.97 ppm and 1.12 ppm
with a coupling constant of 7.2 Hz. There are two quartets, each
accounting for two hydrogens with the same coupling constant at 3.94
and 4.07 ppm. The diastereotopic characteristic of both methyl and
methylene hydrogens of the esters is evident from the above sets of sig-
nals. Mutually coupled one-hydrogen doublets with a coupling constant
of 10.8 Hz appear at 4.06 ppm and 5.25 ppm. There is a three-hydrogen
singlet at 2.28 ppm (Ar Me). Two pairs of AB pseudoquartets, one cen-
tered at 6.97 ppm and 7.07 ppm, another centered at 7.51 ppm and
7.60 ppm, are found. The former pair is due to the p-methylphenyl
ring, while the latter is due to p-chlorophenyl ring.

Synthesis of 4,5-Disubstituted-1,2,3-Selenadiazole
2413
SCHEME 1

2414
S. Saravanan and S. Muthusubramanian
TABLE I Physical Data of Compounds 3 and 4
C%
H%
Compound Yield (%) m.p. (◦C) Molecular formula Calcd. Found Calcd. Found
3a
3b
3c
3d
3e
3f
3g
3h
3i
78
80
73
68
76
87
77
75
64
72
47
55
44
48
52
45
56
47
40
37
137
119
89
C23H27N3O5
C24H29N3O5
64.93 64.87
65.59 65.70
63.28 63.19
60.06 59.92
58.72 58.86
60.06 59.90
60.82 60.98
58.83 58.58
55.88 56.09
54.71 54.88
57.77 57.58
58.60 58.82
56.68 56.59
53.73 53.90
52.60 52.55
53.73 53.94
54.61 54.53
52.94 53.09
6.40
6.65
6.42
5.70
5.57
5.70
5.95
5.76
5.10
4.99
4.85
5.13
4.96
4.30
4.21
4.30
4.58
4.44
3.83
3.76
6.47
6.56
6.48
5.62
5.68
5.87
5.87
5.59
4.95
5.16
4.69
5.26
4.83
4.44
4.34
4.43
4.63
4.56
3.69
3.68
C
24H29N3O6
139
166
156
167
159
132
151
Oil
73–74
82
98
136
104
91
128
102
78
C23H26ClN3O5
C23H26N4O7
C
C
23H26ClN3O5
24H28ClN3O5
C24H28ClN3O6
C23H25Cl2N3O5
C23H25ClN4O7
C22H22N2O4Se
C23H24N2O4Se
3j
4a
4b
4c
4d
4e
4f
4g
4h
4i
C
23H24N2O5Se
C22H21ClN2O4Se
22H21N3O6Se
C
C22H21ClN2O4Se
C23H23ClN2O4Se
C23H23ClN2O5Se
C22H20Cl2N2O4Se 50.21 50.18
C22H20ClN3O6Se 49.22 49.40
4j
The methyl singlet at 2.28 ppm shows HMBC contours with the sig-
nals at 129.73 and 137.75 ppm. The former signal is assigned to the
C-3ꢁ and the latter to the C-4ꢁ, as the former makes a C, H-COSY cross
peak with the signal at 7.07 ppm, which is due to H-3ꢁ. As the signal
at 6.97 ppm makes an H, H-COSY contour with H-3ꢁ, it is assigned to
H-2ꢁ. This signal has a C, H-COSY contour with a signal at 127.84 ppm,
and hence the latter is C-2ꢁ. The H-2ꢁ proton makes an HMBC contour
with the signal at 45.37 ppm, which is now assigned to C-6, and this
correlates with 5.25 ppm (H-6) in C, H-COSY. The atoms C-7 and H-7
are assigned to signals at 61.59 ppm and 4.06 ppm, respectively, which
is confirmed from H, H-COSY and C, H-COSY spectra. The signal at
159.20 ppm has to be assigned either to C-4 or C-5. This signal has
an HMBC contour with aromatic hydrogen at 7.60 ppm. This shows
that the carbon is C-4 and the hydrogen is H-6ꢁ. From H, H-COSY
and C, H-COSY experiments it is very easy to assign signals at 7.51
ppm, 131.26 ppm, and 129.08 ppm to H-7ꢁ, C-6ꢁ, and C-7ꢁ. The other
deshielded carbon signal at 161.82 ppm can be comfortably assigned to
C-5. The H-7ꢁ makes a strong HMBC contour with the signal at 130.38
ppm and a weak one with the signal at 134.92/135.08 ppm, suggesting
the former to be due to C-5ꢁ and the latter to C-8ꢁ. The final signal at
135.08/134.92 ppm is assigned to C-1ꢁ.

2415

2416

2417

2418

2419

2420
S. Saravanan and S. Muthusubramanian
The vicinal coupling constant around 10.8 Hz between the H-6 and
H-7 in both the semicarbazones and the selenadiazoles shows that
these two hydrogens are anti to each other, and this locked confor-
mation seems to be the predominant one. If other conformations also
contribute, the coupling constant should be smaller than this value.
The diastereotopic character due to the asymmetry at C-6 was noticed
even at the terminal methyls of the ester groups. There are two methyl
signals, two methylene signals, and two carbonyl signals for the es-
1
ter groups noted in the H and 13C NMR spectra. The NOESY spec-
trum shows only the normal bonded relationship and no nonbonded
relations.
EXPERIMENTAL
The melting points are uncorrected. NMR spectra were recorded on a
Bruker 300 MHz (UltraShield) NMR spectrometer at room tempera-
ture using CDCl3 as solvent with tetramethylsilane (TMS) as internal
standard. IR spectra were recorded on a JASCO FTIR instrument.
General Procedure for the Preparation of Diethyl
2-(3-Oxo-1,3-diarylpropyl)malonates (2)
The adducts, diethyl 2-(3-oxo-1,3-diarylpropyl)malonates (2) have all
been prepared by reported procedures.8 Diethyl malonate (0.06 mole)
was added to different chalcones 1 (0.06 mole) in ether solution in the
presence of a small amount of sodium ethoxide (0.012 mole) in ethanol,
and the reaction mixture was kept at room temperature for about 20 h
to get 2, which were recrystallised from ethanol.
General Procedure for the Preparation of Diethyl
2-{3-[2-(Aminocarbonyl)hydrazono]-1,3-diarylpropyl}-
malonates (3)
To a warm solution of 0.005 mole of the appropriate ketone (2) in 30 ml
of ethanol, a solution of equimolar amount of semicarbazide hydrochlo-
ride (5.57 g, 0.05 mole) and anhydrous sodium acetate (4.1 g, 0.05 mole)
in 20 ml of water was added and refluxed for 4 h. The solution was
cooled and poured onto crushed ice. The precipitated semicarbazone
was washed with water, dried, and recrystallised from ethanol.

Synthesis of 4,5-Disubstituted-1,2,3-Selenadiazole
2421
General Procedure for the Preparation of Diethyl
2-[aryl(4-Aryl-1,2,3-selenadiazol-5-yl)methyl]-
malonates (4)
2.22 g (0.02 mole) of powdered selenium dioxide was dissolved in glacial
acetic acid by gentle warming. To this warm solution, 0.002 mole of the
appropriate semicarbazone (3) was added at once, and the mixture was
gently heated in a water bath until gas evolution ceased. The selenium
deposited on cooling was removed by filtration, and the filtrate was
poured onto crushed ice, extracted with chloroform, and purified by
column chromatography using silica gel (60–120 mesh).
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