Formation of reagent-selective products from 2-(4,5-dihydrothi- azol-2-ylthio)-1-arylethanone with different nucleophiles

Article abstract of DOI:10.1080/17415993.2010.533772

The reactions of 2-(4,5-dihydrothiazol-2-ylthio)-1-arylethanone with different nucleophiles including semicarbazide hydrochloride, hydroxylamine hydrochloride, hydrazine, ethylenediamine and aminoethanol have been investigated, and the formation of a variety of products with different reagents is highlighted.

Full text of DOI:10.1080/17415993.2010.533772

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Formation of reagent-selective
products from 2-(4,5-dihydrothi-
azol-2-ylthio)-1-arylethanone with
different nucleophiles
S. Saravanan a , P. Mohan a & S. Muthusubramanian a
a School of Chemistry , Madurai Kamaraj University , Madurai ,
625 021 , India
Published online: 29 Nov 2010.
To cite this article: S. Saravanan , P. Mohan & S. Muthusubramanian (2011) Formation of
reagent-selective products from 2-(4,5-dihydrothi- azol-2-ylthio)-1-arylethanone with different
nucleophiles, Journal of Sulfur Chemistry, 32:1, 71-84, DOI: 10.1080/17415993.2010.533772
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Journal of Sulfur Chemistry
Vol. 32, No. 1, February 2011, 71–84
Formation of reagent-selective products from 2-(4,5-dihydrothi-
azol-2-ylthio)-1-arylethanone with different nucleophiles
S. Saravanan†, P. Mohan and S. Muthusubramanian*
School of Chemistry, Madurai Kamaraj University, Madurai 625 021, India
(Received 25 August 2010; final version received 16 October 2010)
The reactions of 2-(4,5-dihydrothiazol-2-ylthio)-1-arylethanone with different nucleophiles including
semicarbazidehydrochloride, hydroxylaminehydrochloride, hydrazine, ethylenediamineandaminoethanol
have been investigated, and the formation of a variety of products with different reagents is highlighted.
S
O
o-Phenylenediamine/
o-aminophenol/
O
HN
NH2NH2·H2SO4
EtOH, reflux
S
N
S
R
R
N
N
H2NCH2CH2NH2/
S
R
H2NCH2CH2OH
R
1
7
6
NH2OH·HCl
PTC condition
PhNHNH2·HCl
Ph
NH
N
R
OH
R
N
S
S
S
S
N
R
HN
Ph
N
R
HO
4
5
Keywords: thiazolidinethiol; nucleophiles; selenium dioxide; thionyl chloride; phase transfer catalyst
1. Introduction
The synthesis of heterocyclic compounds containing selenium/sulfur is of interest not only
because of their synthetic utility for the preparation of alkynes (1), but also because of their
pharmacological properties such as antifungal (2) and antibacterial (3) activities. Some of the
1,2,3-selenadiazole derivatives exhibit antimicrobial, anti-haemostatic and insecticidal activi-
ties (4). 4,5-Bis(p-methoxyphenyl)-1,2,3-thiadiazole possesses platelet aggregation inhibitory
activity in humans (5). Recently, N-substituted hydrazones are found to yield selenadiazole
*Corresponding author. Email: muthumanian2001@yahoo.com
†Present address: Department of Chemistry, A.N.J.A. College, Sivakasi 626 124, India.
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2011 Taylor & Francis
DOI: 10.1080/17415993.2010.533772
http://www.informaworld.com

72 S. Saravanan et al.
on selenium dioxide treatment (6), though conventionally semicarbazones are used as the
precursors (7).
In our continued interest on the synthesis of selenium/sulfur-containing heterocycles (8), we
planned to prepare 1,2,3-selena/thiadiazole linked to thiazolidine ring by a sulfur atom. During
this attempt, we found that 2-(4,5-dihydrothiazol-2-ylthio)-1-arylethanones react differently with
different nucleophiles giving a variety of products. This article summarizes some interesting
results of the related investigations.
2. Results and discussion
2-(4,5-Dihydrothiazol-2-ylthio)-1-arylethanones have been identified as the precursors for the
generationofanewsetofselena/thiodiazoles, whichareeasilypreparedfromsubstitutedphenacyl
bromide and thiazolidinethiol. Thus, the β-ketosulfides (1) were obtained in good yield by treating
thiazolidinethiol with respective phenacyl bromide in DMF–ethanol medium in the presence of
triethylamine. The popular method of preparing 1,2,3-thiadiazole and 1,2,3-selenadiazole is the
treatment of the semicarbazones having α-methylene hydrogens with thionyl chloride and sele-
nium dioxide, respectively (7). Accordingly, the thioketone (1) was treated with semicarbazide
hydrochloride and anhydrous sodium acetate in ethanol to prepare the corresponding semicar-
bazones. When this reaction was carried out under the conventional condition, a pasty mass was
obtained, which was found to be an inseparable mixture of geometrical isomers of the semicar-
bazone. However, if the reaction was effected under phase transfer condition in water:dioxane
medium in the presence of tetrabutylammonium bromide, only one of the geometrical isomer of
the semicarbazone (2) was obtained in good yield with no trace of the other geometrical forms.
Thus, the reaction under phase transfer catalyst seems to be selective.
1
The inspection of the H NMR spectrum of the products 2 reveals the absence of the pair
of triplets showing that the thiazolidine part is not present in the semicarbazone derivative. The
aliphatic region of the proton NMR spectrum consists of only a singlet at around 4.2 ppm. The
13C NMR spectrum of 2d has signals at 157.3, 140.0, 133.3, 132.8, 126.9, 126.5 and 29.4 ppm.
The presence of the semicarbazone unit, an aryl group and a methylene carbon is very much
evident, and the product obtained was found to be not the semicarbazone of 2-(4,5-dihydrothiazol-
2-ylthio)-1-arylethanone, but the bis-semicarbazone of 2,2ꢀ-disulfanedilylbis(1-phenylethanone)
(Scheme 1).
H2N
N
O
O
NH
R
S
N
NH2NHCONH2·HCl
PTC condition
S
S
S
R
N
R
HN
a
b
c
d
R = H
R = CH3
R = C6H5
R = Cl
O
NH2
1
2
Scheme 1. Reaction of 1 with semicarbazide hydrochloride.
The structure of bis-semicarbazone 2 has been unambiguously confirmed by single-crystal X-
ray analysis and the crystal data for 2a (CCDC number 753001) are presented in the Table 1.

Journal of Sulfur Chemistry 73
Table 1. Crystal data and structural refinement for 2a, 3c and 7a.
Parameters
2a
3c
7a
Empirical formula
Formula weight
Temperature
C18H20N6O2S2
416.52
293(2) K
C14H10N2S
238.30
293(2) K
0.71069Å
C11H11NOS
205.27
293(2) K
Wavelength
0.71069Å
0.71073Å
Crystal system, space group Triclinic, P -1
Orthorhombic, Pbc21
a = 5.6512(6) Å,
α = 90.00◦,
Monoclinic, P 21/n
a = 7.3007(7) Å,
α = 90◦,
Unit cell dimensions
a = 14.9782(8)Å,
α = 97.804(11)◦,
b = 15.8713(9) Å,
β = 96.863(9)◦,
c = 17.9615 Å,
γ = 116.856(12)◦
6, 3694.2(4)Å3
1.123 mg/m3
b = 7.6661(7) Å,
β = 90.00◦,
b = 6.0446(6) Å,
β = 96.2170(10)◦,
c = 22.268(2) Å,
γ = 90◦
c = 26.3483(11) Å,
γ = 90.00◦
Z, Volume
4, 1141.48(17)Å3
1.387 mg/m3
4, 976.90(16)Å3
1.396 mg/m3
0.294 mm−1
Density (calculated)
Absorption coefficient
F(000)
0.238 mm−1
0.259 mm−1
1308
496
432
Crystal size
Theta range for data
collection
0.18 × 0.17 × 0.16 mm
0.21 × 0.19 × 0.15 mm
0.37 × 0.36 × 0.16 mm
1.47–25.96◦
3.09–24.97◦
1.84–25.96◦
Index ranges
−18 ≤ h ≤ 18, −19 ≤ k ≤ 0 ≤ h ≤ 6, 0 ≤ k ≤ 94,
−8 ≤ h ≤ 8, ×7 ≤ k ≤ 7,
−27 ≤ l ≤ 27
19, −22 ≤ l ≤ 21
38,397
−1 ≤ l ≤ 31
Reflections collected
Independent reflections
Absorption correction
Refinement method
1076
9595
14,342 [R(int) = 0.0482]
1076 [R(int) = 0.0000]
1912 [R(int) = 0.0245]
Semi-empirical
Full-matrix least-squares
on F2
None
Psi-scans
Full-matrix least-squares
on F2
Full-matrix least-squares
on F2
Data/restraints/parameters 14,342/0/757
1076/1/154
1912/0/128
Flack value = 0.02(13)
Goodness-of-fit on F2
0.946
1.145
1.055
Final R indices [I > 2σ(I)] R1 = 0.0696,
R1 = 0.0288,
wR2 = 0.0716
R1 = 0.0421,
wR2 = 0.0780
0.137 and −0.182eÅ−3
R1 = 0.0374,
wR2 = 0.0957
R1 = 0.0419,
wR2 = 0.0987
0.239 and −0.270eÅ−3
wR2 = 0.1816
R indices (all data)
R1 = 0.1252,
wR2 = 0.2029
Largest diff. peak and hole
0.552 and −0.260eÅ−3
There are three independent molecules in the asymmetric unit and only one of them is shown in
the ORTEP diagram of 2a (Figure 1) with the atomic-numbering scheme. The other two residues
are having the same atomic-numbering scheme with the last alphabets as C/D and E/F. During
the structure analysis, it was observed that the unit cell contains large accessible voids in the
crystal structure, the number of electrons in the voids being ca. 34 with the volume of 843Å3.
This tends to host disordered solvent water molecules. This affects the diffraction pattern, mostly
at low scattering angles; this was corrected with the SQUEEZE program.
It is surprising that the treatment of thioketone with semicarbazide hydrochloride has led to the
formation of a bis-semicarbazone with a disulfide linkage. The thiazolidine ring has been removed
probably by a homolytic cleavage of the bond connecting sulfur and thiazolidine resulting in the
thiyl radical, which would have dimerized to give the disulfide. This disulfide ultimately undergoes
semicarbazone formation. This dissociation seems to be facile as the other radical formed can
itself be stabilized by a tandem process of 1,3-hydrogen migration and hydrogen loss to give a
stable aromatized species – thiazole, as shown in Scheme 2. Unfortunately, there is no evidence
for the formation of thiazole. The NMR spectrum of the crude reaction mixture is very complex in
the aromatic region to locate the signals due to thiazole. Attempts to isolate any byproducts from
the reaction mixture were also not successful. An alternate route for the formation of 2 from 1 is
the attack of the nucleophile on electron-deficient carbon of the imino carbon of the heterocyclic
ring displacing thio group and the corrresponding thiol may undergo dimerization.

74 S. Saravanan et al.
Figure 1. An ORTEP diagram of 2a, with the atom-numbering scheme and 30% probability displacement ellipsoids.
Though the expected semicarbazone with the thioazolidine ring has not been obtained, the prod-
uct formed during the reaction is again a suitable precursor for the generation of sulfur/selenium
heterocycles with two additional nitrogen atoms. A quantitative conversion would probably lead
to two 1,2,3-thia/selenadiazole units linked by the disulfide group. The resultant heterocyclic
systems may assume importance as compounds with disulfide linkage are biologically important.
For example, the disulfide functionality is known to be responsible for the biological activity of
the potassium channel blocking dendrotoxins (9). Several diaryl disulfides have been analyzed for
their second-order nonlinear optical properties, illustrating the applications of this class of com-
pounds (10). Hence, it has been planned to effect the oxidative cyclization using thionyl chloride
and selenium dioxide on the bis-semicarbazones 2.
The semicarbazones 2 upon treatment with thionyl chloride at a low temperature (−5 ◦C)
followed by the removal of excess thionyl chloride gave a single product 3 in 30–40% yield.
The identity of the isolated compound has been arrived at as follows. The proton NMR spectrum
of 3d shows a singlet at 8.65 ppm for one hydrogen and a pair of doublets at 8.0 and 7.5 ppm
each accounting for two hydrogens. The 13C NMR spectrum exhibits six signals at 161.7, 135.3,
130.2, 129.4, 129.2 and 128.6 ppm. The presence of p-chlorophenyl ring, two additional olefinic
carbons, the chemical shift positions of the left out olefinic carbons and the presence of a singlet
at 8.65 ppm in the 1H NMR spectrum all suggest the compound to be 4-(4-chlorophenyl)-1,2,3-
thiadiazole. The melting point of the compound agrees with the reported one (11). Similarly,
compounds 3a–c have been found to be the respective 4-aryl-1,2,3-thiadiazoles (5, 12, 13). The
single-crystal X-ray analysis of the 4-(4-phenylphenyl)thiadiazole (3c) has been carried out and
the results are presented in Table 1, and the ORTEP diagram of 3c is shown in Figure 2 (CCDC
number 753359).

Journal of Sulfur Chemistry 75
O
O
H
N
S
S
N
NH2NHCONH2·HCl
S
S
CH3COONa
R
R
1
R
O
N
S
H
S
S
O
R
H2N
N
O
S
NH
R
N
S
S
N
R
HN
O
NH2
2
Scheme 2. Mechanism for the formation of 2.
Figure 2. An ORTEP diagram of compound 7a, with the atom-numbering scheme and 50% probability displacement
ellipsoids.
The formation of this simple 1,2,3-thiadiazole rather than the expected 4,5-disubsituted thiadi-
azole is surprising and a possible mechanism is postulated in Scheme 3. It is proposed that in the
first step, thionyl chloride reacts with the bis-semicarbazone to give disulfur dichloride and the
heterocyclic sulfoxide ring, probably via a radical mechanism. Disulfur dichloride is a popular
reagent to effect the sulfuration of aromatic rings (14). This reagent has also been used with alu-
minum chloride for the chlorination of the aromatic ring (15). The formation of thiadiazoles from
sulfoxides, as shown in Scheme 3, is well established and has been corroborated with kinetics

76 S. Saravanan et al.
H2N
H2N
O
S
O
O
NH
N
N
N
S
2SOCl2
S
H
S2Cl2
2
H
N
R
R
HN
O
NH2
H2N
H2N
O
O
O
O
H
H
N
H
N
N
N
NH2
N
N
S
O
S
H
S
O
H
H
R
R
R
H
N
H
N
N
H
N
S
S
R
R
3
Scheme 3. Mechanism for the formation of 3 from 2 by the reaction of thionyl chloride.
studies (12). This conversion of sulfoxide system to thiadiazole has been shown to be catalyzed
either by acid or by base and acceptable mechanisms for both routes have been suggested. A
mechanism involving the initial formation of an intermediate (X) (Figure 3) is ruled out as the
presence of the two active methylene hydrogens is essential for further reaction.
The bis-semicarbazone is then subjected to selenium dioxide treatment in THF in the hope of
getting 4,5-disubsituted 1,2,3-selenadiazole. However, the expected oxidative cyclization has not
occurred and the product obtained in 30–40% as a single entity was found to be 5-subsituted-
1,2,3-thiadiazole, very much identical to the product obtained in the earlier case. It is unexpected
O
H2N
O
N
S
H
N
S
2
R
X
Figure 3. Possible intermediate for the formation of 3.

Journal of Sulfur Chemistry 77
to get a sulfur heterocycle by selenium dioxide treatment and it is very clear that one of the sulfur
of the disulfide linkage has entered into the ring and not the selenium as in the conventional
reaction. The formation of the product can be explained by postulating a tentative mechanism as
shown in Scheme 4.
H2N
H2N
H2N
N
O
S
O
O
O
N
NH
R
N
N
N
S
S
SeO2
H
H
S
H
H
N
R
R
R
HN
O
NH2
H2N
O
O
O
H
H
H
N
N
H
N
N
H
N
NH2
N
S
S
O
S
H
R
R
R
N
N
S
H
R
3
Scheme 4. Mechanism for the formation of 3 from 2 by the reaction of selenium dioxide.
The elimination of the alkyl thiol-type compound – by radical or ionic mechanism – can
be proposed in the first step leading to the ring sulfide formation. This can be easily oxidized
to sulfoxide by selenium dioxide. The formation of the thiadiazole from this sulfoxide can be
explainedbyproposingtheestablishedmechanismshownintheprevioustransformationinvolving
thionyl chloride.
Having realized that the reaction of semicarbazide hydrochloride had not yielded the expected
semicarbazone, we tried to prepare the corresponding oximes and hydrazones. The reaction of
hydroxylamine hydrochloride with the thioketone 1 in the presence of phase transfer catalyst
has been found to lead to the formation of the 2((2-(hydroxyimino)-2-phenylethyl)disulfanyl)-
1-arylethanone oximes (4), the bis oximes of the 2,2ꢀ-difulfanedilylbis(1-arylethanone). An
attempted generation of phenylhydrazone from the ketone 1 has also ended with the forma-
tion of the phenylhydrazone of difulfanedilylbis(1-arylethanone) (5) and not that of the ketone 1
(Scheme 5). In both the cases, only one product is obtained quantitatively. The mechanism for
the formation of 4 and 5 is similar to that of 2 as described in Scheme 2.
The reaction of ketone 1 with hydrazine is found to be very interesting.When 1 mol of hydrazine
sulfate is treated with ketone 1a, the reaction gives only one product predominantly under the
reflux condition. The product formed has the molecular ion peak at m/e 266 and intense fragment
ions at m/e 232 and 163. The 1H NMR spectrum has signals at 7.9 and 7.4 ppm in the ratio 2:3 with
two doublets at 3.35 and 3.65 ppm (J = 12.6 Hz), The 13C NMR spectrum has signals at 26.4, 127,

78 S. Saravanan et al.
S
O
o-Phenylenediamine/
o-aminophenol/
O
HN
NH NH .H SO
4
2
2
2
S
N
S
R
R
N
N
H NCH CH NH /
2
S
2
2
2
EtOH, reflux
R
H NCH CH OH
2
2
2
R
1
7
6
NH OH·HCl
2
PhNHNH ·HCl
2
PTC condition
Ph
NH
R
N
OH
R
N
S
S
S
S
N
R
HN
Ph
N
R
HO
4
5
Scheme 5. Reaction of 1 with different nucleophiles.
128, 130, 135 and 151 ppm. All the data suggest that the compound is 3,6-diphenyl-2,7-dihydro-
1,4,5-thiadizepine 6. The spectral data are very much matching with the reported one (16). The
formation of thiadizepine can be formulated as indicated in Scheme 6. There is no evidence for
the formation of SX2, although the mechanism requires the formation of a quantitative amount of
this product. No positive support from the crude product’s NMR spectrum, though the 1H NMR
clearly indicated that some other byproduct has been formed. The compound may not be stable
and would have undergone decomposition and hence could not be isolated during purification.
R
.
.
.
.
.
X
S
X
S
X
O
S
S
NH2NH2·H2SO4
N
X
N
R
R
N
N
S
R
X
R
– SX2
N
S
X =
S
R
R
N
N
6
Scheme 6. Mechanism for the formation of 6.
The peak at m/e 232 in the mass spectrum of 6 is due to M-H2S ion, while the peak at m/e
163 can be accounted for M-C7H5N ion peak, whose formation can be explained as shown in
Scheme 7.
As the reaction of ketone 1a with nucleophiles of the type H2N-X yielded different products
with different H2N-X, it was planned to investigate the reaction of 1a with compounds having two
vicinal nucleophilic centers such as ethylene diamine, o-phenylenediamine, ethanolamine and o-
aminophenol. Here again, the reaction took a different route giving only one product irrespective
of the dinucleophilic reagents employed. The product formed in all the cases was found to be

Journal of Sulfur Chemistry 79
H
S
S
– PhCN
N
H
N
N
R
Scheme 7. Fragmentation pattern of 6.
Figure 4. An ORTEP diagram of 7a, with the atom-numbering scheme. Displacement ellipsoids for non-H atoms are
drawn at the 50% probability level.
1-phenyl-2-(thiazolidin-2-ylidene)ethanone (7a) (17). The compound has its 1H NMR signals at
3.2, 3.9 (7.2 Hz) 10.6, 5.99, 7.8 and 7.4 ppm and 13C NMR signals at 49, 29, 87,169, 186, 127, 128,
130 and 139 ppm. The single-crystal X-ray analysis (CCDC number 784001; Figure 4, Table 1)
also proves the structure of the product unambiguously. The formation of 7a can presumably
be explained as presented in Scheme 8. Thus, the basic character of the ethylene diamine, o-
phenylenediamine, ethanolamine and o-aminophenol seems to dominate over their nucleophilic
character.
O
O
O
H
S
S
N
N
S
N
S
S
S
1a
– 1/8 S8
O
HN
S
7a
Scheme 8. Mechanism for the formation of 7a.

80 S. Saravanan et al.
3. Experimental
Melting points are uncorrected. NMR spectra were recorded on a Bruker 300 MHz instrument
in CDCl3 using TMS as the internal standard. Chemical shifts are given in parts per million (δ-
scale) and coupling constants are given in hertz. The single-crystal X-ray data for 2a and 3c were
collectedonaCCDareadetectordiffractometerwithMoKα radiation(λ = 0.71073 Å)andNonius
MACH3 kappa diffractometer with MoKα radiation (λ = 0.71069 Å), respectively. The structures
were solved by direct methods from SHELXA97 and refined by full-matrix least squares on F2
by SHELXTL97. Column chromatography was carried out in silica gel (60–120 mesh) using
pet ether–ethyl acetate as an eluent. CCDC numbers 753001, 753359 and 784001 contain the
supplementary crystallographic data for 2a, 3c and 7a. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge Crystallographic Data
Centre, Cambridge, UK, or deposit@ccdc.cam.ac.uk).
3.1. General procedure for the preparation of 2-(4,5-dihydro-1,3-thiazol-2-ylsulfanyl)-1-
aryl-1-ethanone 1
To a solution of 4,5-dihydro-1,3-thiazole-2-thiol (0.01 mol) in ethanol (10 ml) and N,N-dimethyl
formamide (5 ml), 0.01 mol of 2-bromo-1-aryl-1-ethanone in ethanol (20 ml) and N,N-dimethyl
formamide (5 ml) was added in portion. Then triethylamine (0.01 mol) was added to the reaction
mixture dropwise, stirred for 2 h and poured onto crushed ice. The product obtained was filtered
and then dried.
3.1.1. 2-(4,5-Dihydro-1,3-thiazol-2-ylsulfanyl)-1-phenyl-1-ethanone (1a)
Yield: 84%; mp = 56 ◦C (reported = 56-57.5 ◦C) (18). 1H NMR (CDCl3) δ: 3.42 (t, J = 8.1 Hz,
2H), 4.18 (t, J = 8.1 Hz, 2H), 4.69 (s, 2H), 7.48 (t, J = 7.5 Hz, 2H), 7.60 (t, J = 7.5 Hz, 1H),
8.00 (d, J = 7.5 Hz, 2H); 13C NMR (CDCl3) δ: 36.1, 40.3, 63.9, 128.5, 128.7, 133.7, 135.4,
164.2, 193.0.
3.1.2. 2-(4,5-Dihydro-1,3-thiazol-2-ylsulfanyl)-1-(4-methylphenyl)-1-ethanone (1b)
1
Yield: 71%; mp = 71 ◦C. H NMR (CDCl3) δ: 2.46 (s, 3H), 3.46 (t, J = 8.1 Hz, 2H) 4.21 (t,
J = 8.1 Hz, 2H), 4.71 (s, 2H), 7.31 (d, J = 8.1 Hz, 2H), 7.94 (d, J = 8.1 Hz, 2H); 13C NMR
(CDCl3) δ: 21.5, 35.9, 40.1, 63.8, 128.5, 129.2, 132.6, 144.5, 164.0, 192.4. Anal. Calcd. for
C12H13NOS2 (251.37): C 57.34, H 5.21, N 5.57; found: C 57.29, H 5.06, N 5.52.
3.1.3. 1-[1,1ꢀ-Biphenyl]-4-yl-2-(4,5-dihydro-1,3-thiazol-2-ylsulfanyl)-1-ethanone (1c)
Yield: 87%; mp = 72 ◦C. 1H NMR (CDCl3) δ: 3.43 (t, J = 7.8 Hz, 2H), 4.19 (t, J = 7.8 Hz, 2H),
4.72 (s, 2H), 7.01–7.56 (m, 9H) ; 13C NMR (CDCl3) δ: 36.5, 40.7, 64.4, 127.7, 127.8, 128.8,
129.4, 129.6, 134.5, 140.0, 146.8, 164.8, 193.1. Anal. Calcd. for C17H15NOS2 (313.44): C 65.14,
H 4.82, N 4.47; found: C 65.11, H 4.94, N 4.44.
3.1.4. 1-(4-Chlorophenyl)-2-(4,5-dihydro-1,3-thiazol-2-ylsulfanyl)-1-ethanone (1d)
1
Yield: 91%; mp = 67 ◦C. H NMR (CDCl3) δ: 4.70 (s, 2H), 3.52 (t, J = 7.8 Hz, 2H), 4.22 (t,
J = 7.8 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 8.01 (d, J = 8.4 Hz, 2H); 13C NMR (CDCl3) δ: 36.1,
39.8, 63.7, 128.8, 129.8, 133.6, 139.9, 163.9, 191.9. Anal. Calcd. for C11H10ClNOS2 (271.79): C
48.61, H 3.71, N 5.15; found: C 48.56, H 3.82, N 5.24.

Journal of Sulfur Chemistry 81
3.2. General procedure for the preparation of 2-[(Z)-2-(2-[(Z)-2-(aminocarbonyl)
hydrazono]-2-arylethyldisulfanyl)-1-arylethylidene]-1-hydrazinecarboxamide (2)
Toasolutionofappropriateketone 1(0.005 mol), semicarbazidehydrochloride(3.90 g, 0.035 mol)
and sodium acetate (2.87 g, 0.035 mol) in a dioxane–water mixture (50 ml, 3:2 v/v), a catalytic
amount of tetrabutylammonium bromide was added. The reaction mixture was stirred at room
temperature for 3 days, poured onto crushed ice, extracted with chloroform and evaporated to
dryness. The ethyl acetate insoluble portion was recrystallized from ethanol to give the respective
semicarbazones.
3.2.1. 2-[(Z)-2-(2-[(Z)-2-(Aminocarbonyl)hydrazono]-2-phenylethyldisulfanyl)-1-
phenylethylidene]-1-hydrazinecarboxamide (2a)
Yield: 85%; mp = 174 ◦C. 1H NMR (CDCl3) δ: 4.12 (s, 4H), 6.70 (bs, 4H), 7.34 (m, 6H), 7.76
(m, 4H), 10.40 (bs, 2H); 13C NMR (CDCl3) δ: 31.4, 126.0, 128.5, 129.4, 136.1, 145.2, 158.5.
Anal. Calcd. for C18H20N6O2S2 (416.52): C 51.90, H 4.84, N 20.18; found: C 51.97, H 4.91, N
20.16.
3.2.2. 2-[(Z)-2-[2-[(Z)-2-(Aminocarbonyl)hydrazono]-2-(4-methylphenyl)ethyl]disulfanyl-1-
(4-methylphenyl)ethylidene]-1-hydrazinecarboxamide (2b)
1
Yield: 56%; mp = 132 ◦C. H NMR (CDCl3) δ: 2.35 (s, 6H), 3.68 (s, 4H), 6.71 (bs, 4H), 7.16
(d, J = 7.8 Hz, 4H), 7.61 (d, J = 7.8 Hz, 4H), 10.48 (bs, 2H); 13C NMR (CDCl3) δ: 20.1, 29.8,
125.2, 127.9, 132.1, 137.7, 147.9, 158.2. Anal. Calcd. for C20H24N6O2S2 (444.57): C 54.03, H
5.44, N 18.90; found: C 54.12, H 5.57, N 18.95.
3.2.3. 2-[(Z)-2-(2-[(Z)-2-(Aminocarbonyl)hydrazono]-2-[1,1ꢀ-biphenyl]-4-ylethyldisulfanyl)-
1-[1,1ꢀ-biphenyl]-4-ylethylidene]-1-hydrazinecarboxamide (2c)
1
Yield: 64%; mp = 178 ◦C. H NMR (CDCl3) δ: 4.16 (s, 4H), 7.21-7.33 (m, 10H), 7.47 (d,
J = 8.4 Hz, 4H), 7.70 (d, J = 8.4 Hz, 4H), 6.58-6.70 (bs, 4H), 10.42 (s, 2H); 13C NMR
(CDCl3) δ: 30.4, 125.7, 125.8, 126.6, 127.9, 134.1,* 138.9, 140.2, 141.7, 157.9. Anal. Calcd.
for C30H28N6O2S2 (568.72): C 63.36, H 4.96, N 14.78; found: C 63.41, H 5.07, N 14.84. (*Two
carbons merge here.)
3.2.4. 2-[(Z)-2-[2-[(Z)-2-(Aminocarbonyl)hydrazono]-2-(4-chlorophenyl)ethyl]disulfanyl-1-
(4-chlorophenyl)ethylidene]-1-hydrazinecarboxamide (2d)
Yield: 68%; mp = 168 ◦C. 1H NMR (CDCl3) δ: 4.16 (s, 4H), 6.65 (bs, 2H), 7.01 (bs, 2H), 7.22
(d, J = 8.4 Hz, 4H), 7.67 (d, J = 8.4 Hz, 4H), 10.50 (s, 2H); 136C NMR (CDCl3) δ: 29.4, 126.5,
126.9, 132.8, 133.3, 140.0, 157.3. Anal. Calcd. for C18H18Cl2N6O2S2 (485.41): C 44.54, H 3.74,
N 14.61; found: C 44.59, H 3.76, N 14.60.
3.3. Reaction of 2-[(Z)-2-(2-[(Z)-2-(aminocarbonyl) hydrazono]-2-arylethyldisulfanyl)-1-
arylethylidene]-1-hydrazinecarboxamide (2) with thionyl chloride
The appropriate semicarbazone (0.001 mol) was added in portion to 10 ml of thionyl chloride
while cooling to −5 ◦C with a freezing mixture. The reaction mixture was allowed to stir for
about 3–4 h. The excess of thionyl chloride was decomposed using aqueous solution of sodium
carbonate and the reaction mixture was extracted with chloroform. The product obtained upon

82 S. Saravanan et al.
purification by column chromatography was found to be 4-aryl-1,2,3-thiadiazole. These 4-aryl
substituted 1,2,3-thiadiazoles have already been reported. (3a): Yield = 42%; mp = 74 ◦C (76–
78 ◦C) (5); (3b): Yield = 38%; mp = 72 (74–76 ◦C) (12); (3c): Yield = 46%; mp = 174–175
(176–177 ◦C) (13); (3d): Yield = 41%; mp = 133 (137 ◦C) (11).
3.4. Reaction of 2-[(Z)-2-(2-[(Z)-2-(aminocarbonyl) hydrazono]-2-arylethyldisulfanyl)-1-
arylethylidene]-1-hydrazinecarboxamide (2) with selenium dioxide
To a solution of the appropriate semicarbazone (0.001 mol) dissolved in dry THF by gentle warm-
ing, 0.01 mol (1.10 g) of powdered selenium dioxide was added in portion. The reaction mixture
was heated to reflux on a water bath for 2 h. The reaction mixture was filtered and the filtrate was
poured onto crushed ice, extracted with chloroform. The product obtained upon purification by
column chromatography was found to be 4-aryl-1,2,3-thiadiazole.
3.5. General procedure for the reaction of 2-(4,5-dihydro-1,3-thiazol-2-ylsulfanyl)-1-aryl-1-
ethanone (1) with hydroxylamine
To a solution of appropriate ketone 1 (0.005 mol), hydroxylamine hydrochloride (0.035 mol) and
sodium acetate (0.035 mol) in a dioxane–water mixture (50 ml, 3:2 v/v), a catalytic amount of
tetrabutylammonium bromide was added. The reaction mixture was stirred at room temperature
for 3 days, poured onto crushed ice, extracted with chloroform and evaporated to dryness. The
ethyl acetate insoluble portion was recrystallized from ethanol to give the respective bis-oximes.
3.5.1. 2-[2-(Hydroxyimino)-2-phenylethyl]disulfanyl-1-phenyl-1-ethanone oxime (4a)
Yield: 74%; mp = 128 ◦C. 1H NMR (CDCl3) δ: 4.21 (s, 4H), 7.37-7.39 (m, 6H), 7.76-7.72 (m,
4H), 10.93 (s,2H); 13C NMR (CDCl3) δ: 32.2, 126.2, 128.4, 129.0, 135.4, 152.9. Anal. Calcd. for
C16H16N2O2S2 (332.44): C 57.81, H 4.85, N 8.43; found: C 56.95, H 4.76, N 8.38.
3.5.2. 2-[2-(Hydroxyimino)-2-(4-methylphenyl)ethyl]disulfanyl-1-(4-methylphenyl)-1-
ethanone oxime (4b)
Yield: 67%; mp = 150 ◦C. 1H NMR (CDCl3) δ: 2.43 (s, 6H), 4.28 (s, 4H), 7.29 (d, J = 8.1 Hz,
4H), 7.73 (d, J = 8.1 Hz, 4H), 10.90 (bs, 2H); 13C NMR (CDCl3) δ: 20.3, 32.2, 126.1, 129.0,
132.3, 138.8, 152.7. Anal. Calcd. for C18H20N2O2S2 (360.50): C 59.97, H 5.59, N 7.77; found:
C 59.84, H 5.62, N 7.69.
3.5.3. 1-[1,1ꢀ-Biphenyl]-4-yl-2-[2-[1,1ꢀ-biphenyl]-4-yl-2-(hydroxyimino)ethyl]disulfanyl-1-
ethanone oxime (4c)
Yield: 78%; mp = 179 ◦C. 1H NMR (CDCl3) δ: 4.14 (s, 4H), 7.32–7.45 (m, 8H),7.57–7.61 (m,
6H), 7.77 (d, J = 8.1 Hz, 4H), 10.90 (s, 2H); 13C NMR (CDCl3) δ: 32.4, 126.5, 126.7, 127.5,
128.8, 129.1, 133.8, 139.8, 141.0, 152.2. Anal. Calcd. for C28H24N2O2S2 (484.63): C 69.39, H
4.99, N 5.78; found: C 69.12, H 4.87, N 5.73.
3.6. General procedure for the reaction of 2-(4,5-dihydro-1,3-thiazol-2-ylsulfanyl)-1-
phenyl-1-ethanone (1a) with phenylhydrazine
To a solution of ketone 1a (0.005 mol), phenylhydrazine hydrochloride (0.035 mol) and sodium
acetate (0.035 mol) in a dioxane–water mixture (50 ml, 3:2 v/v), a catalytic amount of

Journal of Sulfur Chemistry 83
tetrabutylammoniumbromidewasadded.Thereactionmixturewasstirredatroomtemperaturefor
3 days, poured onto crushed ice, extracted with chloroform and evaporated to dryness. The ethyl
acetate insoluble portion was recrystallized from ethanol to give bis-phenylhydrazone. Yield:
1
58%; mp = 146 ◦C. H NMR (CDCl3) δ: 3.04 (s, 4H), 6.86 (td, J = 7.5, 1.2 Hz, 2H), 6.88
(d, J = 7.5 Hz, 4H), 7.21 (t, J = 7.5 Hz, 4H), 7.30–7.49 (m, 6H), 7.80 (d, J = 8.4 Hz, 4H); 13
C
NMR (CDCl3) δ: 21.4, 113.4, 120.4, 125.4, 128.4, 128.8, 129.1, 137.4, 143.0, 144.8. Anal. Calcd.
for C28H26N4S2 (482.67): C 69.68, H 5.43, N 11.61; found: C 69.70, H 5.49, N 11.64.
3.7. General procedure for the reaction of 2-(4,5-dihydro-1,3-thiazol-2-ylsulfanyl)-1-
phenyl-1-ethanone (1a) with hydrazine
A mixture of ketone 1a (0.005 mol), hydrazinium sulfate (0.035 mol) and sodium acetate
(0.035 mol) in 30 ml of ethanol was heated to reflux condition for about 3 h. The reaction mixture
was then poured onto crushed ice, extracted with chloroform and evaporated to dryness. The
ethyl acetate insoluble portion was recrystallized from ethanol to give 3,6-diphenyl-2,7-dihydro-
1,4,5-thiadizepine.18 Yield: 62%; mp = 179 ◦C. 1H NMR (CDCl3) δ: 3.30 (d, J = 13.2 Hz, 2H),
3.66 (d, J = 13.2 Hz, 2H), 7.46 (m, 6H), 7.90 (m, 4H); 13C NMR (CDCl3) δ: 26.4, 127.1, 128.8,
130.2, 135.0, 151.8. GC-mass (m/z): 266.6 (100%), 232.2 (41%), 163.2 (93%). Anal. Calcd. for
C16H14N2S (266.36): C 72.15, H 5.30, N 10.52; found: C 72.17, H 5.36, N 10.55.
3.8. General procedure for the reaction of 2-(4,5-dihydro-1,3-thiazol-2-ylsulfanyl)-1-
phenyl-1-ethanone (1a) with ethylene diamine/o-phenylenediamine/ethanolamine/
o-aminophenol
To a solution of ketone 1a (0.005 mol) and appropriate dinucleophile (0.035 mol) in 30 ml of ethyl
alcohol was heated to reflux condition for about 3 h. The reaction mixture was then poured onto
crushed ice, extracted with chloroform and evaporated to dryness. The ethyl acetate insoluble
portion was recrystallized from ethanol to give 1-phenyl-2-(thiazolidin-2-ylidene)ethanone, 7a.
1
Yield: 75%; mp = 165 ◦C (reported = 168 ◦C) (17). H NMR (CDCl3) δ: 3.28 (t, J = 7.2 Hz,
2H), 3.95 (t, J = 7.2 Hz, 2H), 5.99 (s, 1H), 7.42 (m, 3H), 7.85 (m, 2H), 10.7 (bs, 1H); 13C NMR
(CDCl3) δ: 29.7, 49.7, 87.0, 127.0, 128.2, 130.8, 139.6, 169.8, 186.4. GC-mass (m/z): 204.7
(100%), 176.5 (86%), 144.8 (40%), 104.8 (52%). Anal. Calcd. for C16H14N2S (205.28): C 64.36,
H 5.40, N 6.82; found: C 64.40, H 5.45, N 6.83.
Acknowledgements
The authors thank DST, New Delhi, for assistance under the IRHPA program for the NMR facility.
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