Phenacylsulfonylacetic esters - Source for thiadiazoles, triazoles and oxadiazoles

Article abstract of DOI:10.1002/jhet.5570440116

(Chemical Equation Presented) A new class of thiadiazoles, triazoles and oxadiazoles were prepared from phenacylsulfonylacetic ester by protecting the carbonyl group by oximation. Deoximation was affected by using β-cyclodextrin in the presence of an oxid

Full text of DOI:10.1002/jhet.5570440116

Jan-Feb 2007
93
Phenacylsulfonylacetic esters – Source for thiadiazoles,
triazoles and oxadiazoles
Venkatapuram Padmavathi,* Pinnu Thriveni, Boreddy Chandra Obula Reddy
and Konda Mahesh
Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, India
( Phone : +91-877-2249666 – 303 ; Fax: +91-877-2248499;
E-mail: vkpuram2001@yahoo.com)
Received March 13, 2006
O
O
O
N
O
N
N
O
N
N
O
N
O
O
O
O
O
S
O
O
S
S
O
SH
N
SH
S
SH
S
OMe
NH2
R
R
R
R
11
13
1
12
A new class of thiadiazoles, triazoles and oxadiazoles were prepared from phenacylsulfonylacetic ester
by protecting the carbonyl group by oximation. Deoximation was affected by using ꢀ-cyclodextrin in the
presence of an oxidizing agent.
J. Heterocyclic Chem., 44, 93 (2007).
INTRODUCTION
Scheme I
O
O
The development of simple, facile and efficient
methods for the synthesis of five membered heterocycles
is one of the major challenges in organic synthesis.
Amongst five membered heterocycles thiadiazoles,
triazoles and oxadiazoles have gained importance because
of their intrinsic biological activities and constitute the
structural feature of many bioactive compounds. In fact,
some of them have also emerged as potential drugs [1].
The molecules having triazole and thiadiazine units have
a broad spectrum of antimicrobial and antiparasitic
activities [2]. The 2-mercapto-5-methyl-1,3,4-thiadiazole
is an intermediate for the therapeutically useful antibiotic
cefazolin [3]. Our interest in the development of novel
heterocycles prompted us to study the reactivity of the
methyl ester of phenacylsulfonylacetic acid towards the
development of five membered heterocycles viz., 1,3,4-
thiadiazoles, 1,2,4-triazoles and 1,3,4-oxadiazoles.
O
O
S
NHNH2
X
O
O
O
O
2
S
i
OMe
O
S
1
HN
N
O
O
O
- MeOH
MeO
NH2
N
4
O
S
O
3
i) N2H4. H2O
RESULTS AND DISCUSSION
initially formed (hydrazono-phenyl-ethanesulfonyl)-acetic
acid methyl ester (3) undergoes an intramolecular cyclo-
condensation to 4. In order to achieve the acid hydrazide,
the carbonyl group in 1 was protected by treatment with
hydroxylamine hydrochloride to get hydroxyimino-
phenyl-ethanesulfonyl)-acetic acid methyl ester (5)
(Scheme II). The IR spectra of 5 showed absorption bands
at 1721 (C=O of ester) and at 3338 cm-1 (N-OH of
oxime). Then 5 was stirred with hydrazine hydrate at
room temperature to get (hydroxyimino-phenyl-ethane-
sulfonyl)-acetic acid hydrazide (6). The absence of an
absorption band corresponding to the ester carbonyl group
and the presence of bands at 1665 cm-1 for an amidic
carbonyl group and at 3214 and 3229 cm-1 for NH and
NH2 in the IR spectrum indicates the formation of 6. The
When the methyl ester of phenacylsulfonylacetic acid
(1) was treated with hydrazine hydrate instead of the
expected (oxo-phenyl-ethanesulfonyl)-acetic acid hydra-
zide (2), a cyclic product 6-phenyl-4,7-dihydro-1H-1ꢁ6,
4,5-thiadiazepin-1,1,3(2H)-trione (4) was obtained [4]
(Scheme I). The structure of this compound was
established by its spectral parameters. The 1H NMR
spectrum of 4 showed signals at ꢀ 4.25 and 4.89 ppm for
C2-H and C7-H and a broad singlet at ꢀ 10.65 ppm for NH,
which disappeared on deuteration. The IR spectrum of 4
displayed bands in the regions 1650 (C=O), 1129, 1321
(SO2), 1540 (C=N) and 3258 cm-1 (NH). The 13C NMR
spectrum of 4 showed signals at ꢀ 67.2, 166.3, 154.8 and
61.2 ppm for C-2, C-3, C-6 and C-7. It seems that the

94
V. Padmavathi, P. Thriveni, B. C. O. Reddy and K.Mahesh
Vol 44
Scheme II
NOH
O
O
O
O
O
O
O
S
S
i
OMe
OMe
R
5
R
1
ii
S
NOH
O
O
O
NHNH2
R
6
iii
NOH
O
O
O
-
S
NHNHCSK
S
R
7
v
vi
S
iv
NOH
O
NOH
O
NOH
O
N
N
N
N
N
N
O
O
O
S
S
S
SH
N
SH
O
SH
NH2
R
R
R
10
8
9
vii
vii
S
vii
O
O
O
N
N
N
N
N
N
O
O
O
O
O
O
S
S
O
SH
S
SH
N
SH
NH2
R
R
R
11
12
13
a
b
c
R = H
R = Me
R = Cl
i) NH2OH.HCl / EtOH ii) N2H4.H2O / Pyridine / EtOH iii) KOH / CS2 / EtOH
iv) AcOH v) N2H4.H2O vii) ꢀ-CD / H2O
vi) H+
potassium dithiocarbazate of the acid hydrazide (7) was
prepared by treating 6 with carbon disulfide in the
presence of potassium hydroxide under ultrasonic
conditions. In refluxing acetic acid, the latter cyclized to
give 1-phenyl-2-{[(5-sulfanyl-1,3,4-thiadiazol-2-yl)methyl]-
sulfonyl}-1-ethanone oxime (8). Treatment of 7 with
hydrazine hydrate produced 2-{[(4-amino-5-sulfanil-4H-
1,2,4-triazol-3-yl)methyl]sulfonyl}-1-phenyl-1-ethanone
oxime (9). Similarly base catalyzed hydrolysis of 7
resulted in 1-phenyl-2-{[(5-sulfanyl-1,3,4-oxadiazol-2-
yl)methyl]sulfonyl}-1-ethanone oxime (10). The IR spectra
of 8-10 displayed absorption bands around 1634 cm-1 for
C=N apart from bands due to other functional groups. The
1H NMR spectra showed a singlet at ꢀ 10.23-10.43 ppm
for SH apart from signals due to methylene protons.
However the compound 9 exhibited signals at ꢀ 5.60 ppm
There were different methods in the literature for the
deoximation of oxime group [5-20]. We have adopted
the deoximation reaction of 8-10 using mild oxidizing
agent 2-iodoxybenzoic acid catalyzed by ꢀ-cyclo-
dextrin in water at room temperature. The products
obtained were identified as 1-phenyl-2-{[(5-sulfanyl-
1,3,4-thiadiazol-2-yl)methyl]sulfonyl}-1-ethanone (11),
2-{[(4-amino-5-sulfanil-4H-1,2,4-triazol-3-yl)methyl]-
sulfonyl}-1-phenyl-1-ethanone (12) and 1-phenyl-2-
{[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methyl]sulfonyl}-1-
ethanone (13), respectively. The IR spectra of these
compounds displayed an additional band due to C=O
1
at 1680 cm-1 apart from other absorption bands. The H
NMR spectra of these compounds displayed two
singlets at ꢀ 4.70-4.79 and 4.62-4.72 ppm due to
methylene protons flanked between Ar-CO-SO2 and
SO2-heterocyclic units. The structure of the
compounds was further confirmed by 13C NMR
spectra.
for NH2, which disappeared on deuteration.
The
structures of these compounds were further confirmed by
13C NMR spectra.

Jan-Feb 2007
Phenacylsulfonylacetic esters – Source for thiadiazoles, triazoles and oxadiazoles
95
(OCH3), 56.2 (SO2-CH2), 58.1 (CH2-SO2), 129.1, 130.3, 130.8,
132.6 (Ar-C), 165.9 (C=NOH), 168.6 (COOCH3). Anal. Calcd.
for C12H15NO5S: C, 50.52; H, 5.30; N, 4.91. Found: C, 50.60; H,
5.28; N, 4.96.
CONCLUSION
The desired thiadiazoles, triazoles and oxadiazoles were
prepared from phenacylsulfonylacetic esters by protecting
the carbonyl group. Thus the oximation of carbonyl group
and deoximation with ꢀ-cyclodextrin in the presence of
[(4-Chloro-phenyl)-hydroxyimino-ethanesulfonyl]-acetic
acid methyl ester (5c). White solid, Yield 0.27 g (90%), mp 98-
100 °C; ir: 1150, 1327 (SO2), 1632 (C=N), 1722 (C=O), 3339
(OH) cm-1; 1H nmr (CDCl3): ꢂH 3.69 (s, 3H, OCH3), 4.38 (s, 2H,
SO2-CH2), 4.95 (s, 2H, CH2-SO2), 7.22-7.41 (m, 4H, Ar-H),
12.26 (s, 1H, OH); 13C nmr (CDCl3): ꢂC 54.0 (OCH3), 56.9 (SO2-
CH2), 58.6 (CH2-SO2), 129.4, 130.7, 134.8, 136.3 (Ar-C), 166.9
(C=NOH), 169.6 (COOCH3). Anal. Calcd. for C11H12ClNO5S: C,
43.21; H, 3.96; N, 4.58. Found: C, 43.27; H, 3.91; N, 4.55.
(Hydroxyimino-aryl-ethanesulfonyl)-acetic acid hydrazide
(6): General Procedure. To a solution of 5 (0.271 g, 1 mmol) in
absolute ethanol, hydrazine hydrate (0.22 ml, 4.5 mmol) and
pyridine (0.4 ml) were added and stirred for 3 h at room
temperature. The resultant solid was collected by filtration and
recrystallized from ethanol.
(Hydroxyimino-phenyl-ethanesulfonyl)-acetic acid hydrazide
(6a). White solid, Yield 0.23 g (79%), mp 165-166 °C; ir: 1135,
1312 (SO2), 1623 (C=N), 1665 (C=O), 3214 (NH), 3229 (NH2),
3331 (OH) cm-1; 1H nmr (DMSO-d6): ꢂH 3.96 (s, 2H, SO2-CH2),
4.91(s, 2H, CH2-SO2), 5.15 (br s, 2H, NH2), 7.25-7.31 (m, 5H,
Ar-H), 9.52 (br s, 1H, NH), 12.16 (s, 1H, OH); 13C nmr (DMSO-
d6): ꢂC 55.8 (SO2-CH2), 57.7 (CH2-SO2), 128.7, 129.8, 130.6,
131.5 (Ar-C), 166.2 (C=NOH), 168.4 (CONHNH2). Anal. Calcd.
for C10H13N3O4S: C, 44.27; H, 4.83; N, 15.49. Found: C, 44.21;
H, 4.80; N, 15.55.
(Hydroxyimino-p-tolyl-ethanesulfonyl)-acetic acid hydrazide
(6b). White solid, Yield 0.23 g (76%), mp 171-173 °C; ir: 1136,
1320 (SO2), 1626 (C=N), 1650 (C=O), 3210 (NH), 3225 (NH2),
3330 (OH) cm-1; 1H nmr (DMSO-d6): ꢂH 2.34 (s, 3H, CH3), 3.94
(s, 2H, SO2-CH2), 4.80 (s, 2H, CH2-SO2), 4.98 (br s, 2H, NH2),
7.16-7.23 (m, 4H, Ar-H), 9.23 (br s, 1H, NH), 11.92 (s, 1H,
OH); 13C nmr (DMSO-d6): ꢂC 20.6 (Ar-CH3), 56.1 (SO2-CH2),
58.4 (CH2-SO2), 129.2, 130.4, 131.7, 132.8 (Ar-C), 166.4
(C=NOH), 168.7 (CONHNH2). Anal. Calcd. for C11H15N3O4S:
C, 46.30; H, 5.30; N, 14.73. Found: C, 46.35; H, 5.33; N, 14.78.
[(4-Chloro-phenyl)-hydroxyimino-ethanesulfonyl]-acetic
acid hydrazide (6c). White solid, Yield 0.24 g (75%), mp 178-
180 °C; ir: 1136, 1313 (SO2), 1624 (C=N), 1655 (C=O), 3212
(NH), 3223 (NH2), 3327 (OH) cm-1; 1H nmr (DMSO-d6): ꢂH 3.99
(s, 2H, SO2-CH2), 4.94 (s, 2H, CH2-SO2), 5.21 (br s, 2H, NH2),
7.25-7.39 (m, 4H, Ar-H), 9.66 (br s, 1H, NH), 12.25 (s, 1H,
OH); 13C nmr (DMSO-d6): ꢂC 56.8 (SO2-CH2), 58.9 (CH2-SO2),
129.6, 131.2, 133.2, 138.3 (Ar-C), 166.8 (C=NOH), 168.9
(CONHNH2). Anal. Calcd. for C10H12ClN3O4S: C, 39.28; H,
3.96; N, 13.74. Found: C, 39.33; H, 4.00; N, 13.78.
oxidizing agent provides
a
simple and efficient
methodology for regiospecific synthesis of heterocycles.
EXPERIMENTAL
Melting points were determined in open capillaries on a Mel-
Temp apparatus. The purity of the compounds was checked by
TLC (Silica gel H, BDH, ethyl acetate-hexane, 1:3). IR spectra
were recorded on a Thermo Nicolet IR 200 FT-IR in KBr
pellets. 1H NMR spectra were recorded at 300 MHz on a Varian
EM-360 spectrometer. 13C NMR spectra were run on a Varian
VXR spectrometer operating at 75.5 MHz. All chemical shifts
are reported in ppm from TMS as an internal standard. Mass
spectra were recorded on a Joel JMS-D 300 instrument at 70 eV.
Elemental analyses were performed using a Perkin-Elmer 240 C
elemental analyzer. The starting compound methyl ester of
phenacylsulfonylacetic acid
1 was prepared by standard
procedure [21].
6-Phenyl-4,7-dihydro-1H-1ꢁ6,4,5-thiadiazepin-1,1,3(2H)-
trione (4): General Procedure. A mixture of 1 (0.051 g, 0.2
mmol), hydrazine hydrate (0.02 ml, 0.4 mmol) and methanol (15
ml) was refluxed for 10 h after which the solution was cooled
and the solid separated was collected by filtration, dried and
recrystallized from methanol.
6-Phenyl-4,7-dihydro-1H-1ꢁ6,4,5-thiadiazepin-1,1,3(2H)-
trione (4). White crystals, Yield 0.030 g (64%), mp 301-303 °C;
ir: 1129, 1321(SO2), 1540 (C=N), 1650 (C=O), 3258 (NH) cm-1;
1H nmr (DMSO-d6): ꢂH 4.25 (s, 2H, C2-H), 4.89 (s, 2H, C7-H),
7.22-7.63 (m, 5H, Ar-H), 10.65 (bs, 1H, NH); 13C nmr (DMSO-
d6): ꢂC 61.2 (C7), 67.2 (C2), 154.8 (C6), 166.3 (C3); ms: m/z 238
(M+.). Anal. Calcd. for C10H10N2O3S: C, 50.41; H, 4.23; N,
11.76. Found: C, 50.50; H, 4.27; N, 11.82.
(Hydroxyimino-aryl-ethanesulfonyl)-acetic acid methyl
ester (5): General Procedure. To a solution of methyl ester of
phenacylsulfonylacetic acid 1 (0.26 g, 1 mmol) in ethanol,
hydroxylamine hydrochloride (0.347 g, 5 mmol) and pyridine
(0.2 ml) were added and refluxed for 8 h over a water bath after
which the solution was poured into crushed ice and the resultant
solid was purified by recrystallization from ethanol.
(Hydroxyimino-phenyl-ethanesulfonyl)-acetic acid methyl
ester (5a). White solid, Yield 0.23 g (84%), mp113-115 °C; ir:
1148, 1325 (SO2), 1625 (C=N), 1721 (C=O), 3338 (OH) cm-1;
1H nmr (CDCl3): ꢂH 3.67 (s, 3H, OCH3), 4.35 (s, 2H, SO2-CH2),
4.92 (s, 2H, CH2-SO2), 7.32-7.61 (m, 5H, Ar-H), 12.15 (s, 1H,
OH); 13C nmr (CDCl3): ꢂC 53.3 (OCH3), 56.5 (SO2-CH2), 57.3
(CH2-SO2), 128.6, 129.3, 130.5, 131.4 (Ar-C), 166.3 (C=NOH),
169.2 (COOCH3). Anal. Calcd. for C11H13NO5S: C, 48.70; H,
4.83; N, 5.16. Found: C, 48.79; H, 4.86; N, 5.22.
Potassium dithiocarbazate (7): General Procedure. To a
mixture of potassium hydroxide (0.112 g, 2 mmol) and 6 (0.271
g, 1 mmol) in absolute ethanol, carbon disulfide (0.24 ml, 4
mmol) was added and sonicated for 12 h. The separated solid
was collected by filtration and dried.
Potassium Nꢃ-[2-(2-hydroxyimino-2-phenyl-ethanesulfonyl)-
acetyl]-hydrazine carbodithioate (7a). White solid, Yield 0.28
g (72%); ir: 1137, 1315 (SO2), 1224 (C=S), 1627 (C=N), 1671
(C=O), 3219 (NH), 3340 (OH) cm-1. Anal. Calcd. for
C11H12KN3O4S3: C, 34.27; H, 3.14; N, 10.90. Found: C, 34.31;
H, 3.18; N, 10.95.
(Hydroxyimino-p-tolyl-ethanesulfonyl)-acetic acid methyl
ester (5b). White solid, Yield 0.25 g (88%), mp 122-123 °C; ir:
1146, 1335 (SO2), 1628 (C=N), 1720 (C=O), 3335 (OH) cm-1;
1H nmr (CDCl3): ꢂH 2.31 (s, 3H, CH3), 3.65 (s, 3H, OCH3), 4.33
(s, 2H, SO2-CH2), 4.89 (s, 2H, CH2-SO2), 7.11-7.31 (m, 4H, Ar-
H), 11.93 (s, 1H, OH); 13C nmr (CDCl3): ꢂC 20.4 (Ar-CH3), 53.6
Potassium Nꢃ-[2-(2-hydroxyimino-2-(4-methyl-phenyl)-
ethanesulfonyl)-acetyl]-hydrazine carbodithioate (7b). White

96
V. Padmavathi, P. Thriveni, B. C. O. Reddy and K.Mahesh
Vol 44
solid, Yield 0.30 g (75%); ir: 1132, 1317 (SO2), 1225 (C=S),
1623 (C=N), 1679 (C=O), 3221 (NH), 3332 (OH) cm-1. Anal.
Calcd. for C12H14KN3O4S3: C, 36.07; H, 3.53; N, 10.52. Found:
C, 36.10; H, 3.56; N, 10.57.
Potassium Nꢀ-[2-(2-hydroxyimino-2-(4-chloro-phenyl)-
ethanesulfonyl)-acetyl]-hydrazine carbodithioate (7c). White
solid, Yield 0.33 g (79%); ir: 1135, 1320 (SO2), 1227 (C=S),
1629 (C=N), 1681 (C=O), 3225 (NH), 3342 (OH) cm-1. Anal.
Calcd. for C11H11ClKN3O4S3: C, 31.46; H, 2.64; N, 10.01.
Found: C, 31.48; H, 2.68; N, 10.05.
1-Aryl-2-{[(5-sulfanyl-1,3,4-thiadiazol-2-yl)methyl]sulfonyl}-
1-ethanone oxime (8): General Procedure. A mixture of 7
(0.371 g, 1 mmol) and acetic acid (4 ml) were refluxed for 24 h.
The contents of the flask were cooled and poured into crushed
ice. The solid obtained was collected by filtration, dried and
recrystallized from 2-propanol.
1-Phenyl-2-{[(5-sulfanyl-1,3,4-thiadiazol-2-yl)methyl]-
sulfonyl}-1-ethanone oxime (8a). White solid, Yield 0.21 g
(65%), mp 192-194 °C; ir: 1128, 1330 (SO2), 1633 (C=N), 2559
(SH), 3336 (OH) cm-1; 1H nmr (DMSO-d6): ꢁH 4.65 (s, 2H, SO2-
CH2), 4.92 (s, 2H, CH2-SO2), 7.31-7.62 (m, 5H, Ar-H), 10.23 (s,
1H, SH), 12.21 (s, 1H, OH); 13C nmr (DMSO-d6): ꢁC 55.8 (SO2-
CH2), 58.6 (CH2-SO2), 128.6, 129.5, 130.8, 131.2 (Ar-C), 159.8
(C5), 166.1 (C=NOH), 169.1 (C2); ms: m/z 329 (M+.). Anal.
Calcd. for C11H11N3O3S3 : C, 40.11; H, 3.37; N, 12.76. Found: C,
40.15; H, 3.34; N, 12.83.
2-{[(4-Amino-5-sulfanil-4H-1,2,4-triazol-3-yl)methyl]-
sulfonyl}-1-p-tolyl-1-ethan-one oxime (9b). White solid, Yield
0.23 g (67%), mp 153-155 °C; ir: 1144, 1329 (SO2), 1631
(C=N), 2631 (SH), 3284 (NH2), 3340 (OH) cm-1; 1H nmr
(DMSO-d6): ꢁH 2.26 (s, 3H, CH3), 4.67 (s, 2H, SO2-CH2), 4.87
(s, 2H, CH2-SO2), 5.54 (br s, 1H, NH2), 7.27-7.52 (m, 4H, Ar-
H), 10.31 (s, 1H, SH), 12.28 (s, 1H, OH); 13C nmr (DMSO-d6):
ꢁC 20.6 (CH3), 48.6 (SO2-CH2), 59.1 (CH2-SO2), 128.2, 129.1,
130.3, 140.1 (Ar-C), 148.4 (C5), 165.2 (C=NOH), 166.9 (C3).
Anal. Calcd. for C12H15N5O3S2: C, 42.22; H, 4.43; N, 20.51.
Found: C, 42.19; H, 4.40; N, 20.55.
2-{[(4-Amino-5-sulfanil-4H-1,2,4-triazol-3-yl)methyl]-
sulfonyl}-1-(4-chloro-phenyl)-1-ethanone oxime (9c). White
solid, Yield 0.26 g (71%), mp 174-176 °C; ir: 1146, 1339 (SO2),
1
1634 (C=N), 2644 (SH), 3287 (NH2), 3337 (OH) cm-1; H nmr
(DMSO-d6): ꢁH 4.77 (s, 2H, SO2-CH2), 4.93 (s, 2H, CH2-SO2),
7.40-7.82 (m, 4H, Ar-H), 5.63 (br s, 1H, NH2), 10.36 (s, 1H,
SH), 12.44 (s, 1H, OH); 13C nmr (DMSO-d6): ꢁC 49.1 (SO2-
CH2), 59.9 (CH2-SO2), 129.0, 129.3, 130.6, 136.3 (Ar-C), 150.1
(C5), 166.1 (C=NOH), 167.8 (C3). Anal. Calcd. for
C11H12ClN5O3S2: C, 36.51; H, 3.34; N, 19.36. Found: C, 36.46;
H, 3.30; N, 19.42.
1-Aryl-2-{[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methyl]sulfonyl}-
1-ethanone oxime (10): General Procedure. Potassium salt 7
(0.371 g, 1 mmol) was dissolved in 6 ml of water and acidified
with 1-2 ml of con. hydrochloric acid. The regenerated solid was
collected by filtration, dried and purified by recrystallization
from 2-propanol.
1-Phenyl-2-{[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methyl]-
sulfonyl}-1-ethanone oxime (10a). White solid, Yield 0.23 g
(74%), mp 185-187 °C; ir: 1125, 1328 (SO2), 1630 (C=N), 2578
(SH), 3339 (OH) cm-1; 1H nmr (DMSO-d6): ꢁH 4.72 (s, 2H, SO2-
CH2), 4.89 (s, 2H, CH2-SO2), 7.28-7.59 (m, 5H, Ar-H), 10.28 (s,
1H, SH), 12.39 (s, 1H, OH); 13C nmr (DMSO-d6): ꢁC 54.8 (SO2-
CH2), 58.9 (CH2-SO2), 128.5, 129.1, 130.6, 131.3 (Ar-C), 158.7
(C5), 165.2 (C=NOH), 166.2 (C2); ms: m/z 313 (M+.). Anal.
Calcd. for C11H11N3O4S2: C, 42.16; H, 3.54; N, 13.41. Found: C,
42.11; H, 3.56; N, 13.35.
1-p-Tolyl-2-{[(5-sulfanyl-1,3,4-thiadiazol-2-yl)methyl]-
sulfonyl}-1-ethanone oxime (8b). White solid, Yield 0.25 g
(69%), mp 210-212°C; ir: 1130, 1332 (SO2), 1634 (C=N), 2562
1
(SH), 3334 (OH) cm-1; H nmr (DMSO-d6): ꢁH 2.24 (s, 3H,
CH3), 4.63 (s, 2H, SO2-CH2), 4.89 (s, 2H, CH2-SO2), 7.29-7.42
(m, 4H, Ar-H), 10.28 (s, 1H, SH), 11.89 (s, 1H, OH); 13C nmr
(DMSO-d6): ꢁC 20.2 (CH3), 55.6 (SO2-CH2), 58.4 (CH2-SO2),
128.2, 129.1, 131.2, 134.6 (Ar-C), 158.2 (C5), 163.7 (C=NOH),
167.6 (C2). Anal. Calcd. for C12H13N3O3S3: C, 41.97; H, 3.82; N,
12.23. Found: C, 41.88; H, 3.86; N, 12.31.
1-(4-Chlorophenyl)-2-{[(5-sulfanyl-1,3,4-thiadiazol-2-yl)-
methyl]sulfonyl}-1-ethanone oxime (8c).White solid, Yield 0.23 g
(63%), mp 204-206 °C; ir: 1132, 1335 (SO2), 1638 (C=N), 3332
1-p-Tolyl-2-{[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methyl]-
sulfonyl}-1-ethanone oxime (10b). White solid, Yield 0.25 g
(76%), mp 194-196 °C; ir: 1129, 1330 (SO2), 1626 (C=N), 2580
1
(OH), 2564 (SH) cm-1; H nmr (DMSO-d6): ꢁH 4.68 (s, 2H, SO2-
CH2), 4.95 (s, 2H, CH2-SO2), 7.34-7.68 (m, 4H, Ar-H), 10.43 (s, 1H,
SH), 12.31 (s, 1H, OH); 13C nmr (DMSO-d6): ꢁC 55.9 (SO2-CH2),
58.8 (CH2-SO2), 128.9, 129.3, 130.4, 135.9 (Ar-C), 161.5 (C5),
164.9 (C=NOH), 167.6 (C2). Anal. Calcd. for C11H10ClN3O3S3: C,
36.31; H, 2.77; N, 11.55. Found: C, 36.36; H, 2.82; N, 11.63.
1
(SH), 3341 (OH) cm-1; H nmr (DMSO-d6): ꢁH 2.25 (s, 3H,
CH3), 4.69 (s, 2H, SO2-CH2), 4.86 (s, 2H, CH2-SO2), 7.30-7.68
(m, 4H, Ar-H), 10.30 (s, 1H, SH), 11.91 (s, 1H, OH); 13C nmr
(DMSO-d6): ꢁC 20.4 (CH3), 55.1 (SO2-CH2), 59.2 (CH2-SO2),
128.2, 129.1, 130.2, 139.8 (Ar-C), 157.9 (C5), 164.1 (C=NOH),
165.8 (C2). Anal. Calcd. for C12H13N3O4S2: C, 44.02; H, 4.00; N,
12.84. Found: C, 43.95; H, 3.98; N, 12.75.
1-(4-Chloro-phenyl)-2-{[(5-sulfanyl-1,3,4-oxadiazol-2-yl)-
methyl]sulfonyl}-1-ethanone oxime (10c). White solid, Yield
0.26 g (75%), mp 198-200 °C; ir: 1132, 1340 (SO2), 1623
(C=N), 2584 (SH), 3338 (OH) cm-1; 1H nmr (DMSO-d6): ꢁH 4.74
(s, 2H, SO2-CH2); 4.91 (s, 2H, CH2-SO2); 7.40-7.71 (m, 4H, Ar-
H); 10.32 (s, 1H, SH); 12.48 (s, 1H, OH); 13C nmr (DMSO-d6):
ꢁC 54.3 (SO2-CH2), 58.5 (CH2-SO2), 128.9, 129.2, 130.2, 135.2
(Ar-C), 159.2 (C5), 164.6 (C=NOH), 166.9 (C2). Anal. Calcd. for
C11H10ClN3O4S2: C, 37.99; H, 2.90; N, 12.08. Found: C, 38.07;
H, 2.93; N, 12.03.
2-{[(4-Amino-5-sulfanil-4H-1,2,4-triazol-3-yl)methyl]sulfonyl}-
1-aryl-1-ethanone oxime (9): General Procedure. To a
solution of 7 (0.37 g, 1 mmol) in 6 ml of water, hydrazine
hydrate (0.1 ml, 2 mmol) was added and refluxed for 8-9 h. The
contents of the flask were cooled, diluted with water and
acidified with 2 ml of acetic acid. The separated solid was
collected by filtration, dried and recrystallized from 2-propanol.
2-{[(4-Amino-5-sulfanil-4H-1,2,4-triazol-3-yl)methyl]sulfonyl}-
1-phenyl-1-ethanone oxime (9a). White solid, Yield 0.22 g
(66%), mp 165-167 °C; ir: 1141, 1337 (SO2), 1628 (C=N), 2624
(SH), 3280 (NH2), 3335 (OH) cm-1; 1H nmr (DMSO-d6): ꢁH 4.73
(s, 2H, SO2-CH2), 4.91 (s, 2H, CH2-SO2), 5.60 (br s, 1H, NH2),
7.32-7.68 (m, 5H, Ar-H), 10.41 (s, 1H, SH), 12.36 (s, 1H, OH);
13C nmr (DMSO-d6): ꢁC 48.4 (SO2-CH2), 59.6 (CH2-SO2), 128.5,
129.0, 130.8, 131.4 (Ar-C), 149.3 (C5), 164.9 (C=NOH), 167.4
(C3); ms: m/z 327 (M+.). Anal. Calcd. for C11H13N5O3S2: C,
40.36; H, 4.00; N, 21.39. Found: C, 40.25; H, 3.95; N, 21.46.
1-Aryl-2-{[(5-sulfanyl-1,3,4-thiadiazol-2-yl)methyl]sulfonyl}-1-
ethanone (11); 2-{[(4-Amino-5-sulfanil-4H-1,2,4-triazol-3-
yl)methyl]sulfonyl}-1-aryl-1-ethanone (12); 1-Aryl-2-{[(5-
sulfanyl-1,3,4-oxadiazol-2-yl)methyl]sulfonyl}-1-ethanone (13):

Jan-Feb 2007
Phenacylsulfonylacetic esters – Source for thiadiazoles, triazoles and oxadiazoles
97
General Procedure. To a solution of ꢀ-cyclodextrin (0.1134
g, 0.1 mmol) in distilled water (15 ml), appropriate oxime 8
or 9 or 10 (1 mmol) dissolved in acetone (2 ml) and 2-
iodoxy-benzoic acid (0.28 g, 1 mmol) were added and stirred
at room temperature for 14-16 h. The reaction mixture was
extracted with ethyl acetate, and concentrated under vacuum.
The crude product obtained was purified by column
chromatography on silica gel (60-120 mesh) using ethyl
acetate -hexane (9:1).
5.67 (br s, 2H, NH2), 7.53-7.79 (m, 4H, Ar-H), 10.30 (s, 1H,
SH); 13C nmr (DMSO-d6): ꢁC 43.1 (SO2-CH2), 60.8 (CH2-SO2),
128.8, 130.0, 135.5, 138.2 (Ar-C), 144.5 (C5), 169.1 (C3), 196.1
(C=O). Anal. Calcd. for C11H11ClN4O3S2: C, 38.09; H, 3.20; N,
16.15. Found: C, 38.00; H, 3.23; N, 16.24.
1-Phenyl-2-{[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methyl]sul-
fonyl}-1-ethanone (13a). White solid, Yield 0.20 g (68%),
mp199-201 °C; ir: 1123, 1331 (SO2), 1626 (C=N), 1684 (C=O),
1
2579 (SH) cm-1; H nmr (DMSO-d6): ꢁH 4.63 (s, 2H, SO2-CH2),
1-Phenyl-2-{[(5-sulfanyl-1,3,4-thiadiazol-2-yl)methyl]sul-
fonyl}-1-ethanone (11a). White solid, Yield 0.24 g (77%), mp
214-216 °C; ir: 1130, 1335 (SO2), 1628 (C=N), 1680 (C=O),
4.75 (s, 2H, CH2-SO2), 7.38-7.65 (m, 5H, Ar-H), 10.25 (s, 1H,
SH); 13C nmr (DMSO-d6): ꢁC 54.8 (SO2-CH2), 58.4 (CH2-SO2),
128.6, 129.0, 130.6, 131.2 (Ar-C), 158.7 (C5), 166.4 (C2), 196.2
(C=O); ms: m/z 298 (M+.). Anal. Calcd. for C11H10N2O4S2: C,
44.28; H, 3.38; N, 9.39. Found: C, 44.34; H, 3.42; N, 9.45.
1-p-Tolyl-2-{[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methyl]sul-
fonyl}-1-ethanone (13b). White solid, Yield 0.19 g (64%), mp
205-207 °C; ir: 1134, 1328 (SO2), 1631 (C=N), 1682 (C=O),
1
2561 (SH) cm-1; H nmr (DMSO-d6): ꢁH 4.62 (s, 2H, SO2-CH2),
4.70 (s, 2H, CO-CH2-SO2), 7.37-7.79 (m, 5H, Ar-H), 10.24 (s,
1H, SH); 13C nmr (DMSO-d6): ꢁC 52.8 (SO2-CH2), 61.8 (CH2-
SO2), 128.4, 129.3, 132.9, 137.5 (Ar-C), 164.1 (C5), 166.8 (C2),
196.6 (C=O); ms: m/z 314 (M+.). Anal. Calcd. for C11H10N2O3S3:
C, 42.02; H, 3.21; N, 8.91. Found: C, 42.11; H, 3.24; N, 8.97.
1-p-Tolyl-2-{[(5-sulfanyl-1,3,4-thiadiazol-2-yl)methyl]-
sulfonyl}-1-ethanone (11b). White solid, Yield 0.24 g (73%),
mp 222-224 °C; ir: 1127, 1332 (SO2), 1625 (C=N), 1676 (C=O),
1
2581 (SH) cm-1; H nmr (DMSO-d6): ꢁH 2.28 (s, 3H, CH3), 4.66
(s, 2H, SO2-CH2), 4.71 (s, 2H, CH2-SO2), 7.59-7.73 (m, 4H, Ar-
H), 10.28 (s,1H, SH); 13C nmr (DMSO-d6): ꢁC 20.8 (CH3), 54.9
(SO2-CH2), 58.8 (CH2-SO2), 128.3, 129.2, 131.2, 141.9 (Ar-C),
159.2 (C5), 166.8 (C2), 193.2 (C=O). Anal. Calcd. for
C12H12N2O4S2: C, 46.14; H, 3.87; N, 8.97. Found: C, 46.09; H,
3.91; N, 9.05.
1
2560 (SH) cm-1; H nmr (DMSO-d6): ꢁH 2.29 (s, 3H, CH3), 4.69
(s, 2H, SO2-CH2), 4.72 (s, 2H, CH2-SO2), 7.40-7.68 (m, 4H, Ar-
H), 10.26 (s, 1H, SH); 13C nmr (DMSO-d6): ꢁC 21.2 (CH3), 51.9
(SO2-CH2), 60.7 (CH2-SO2), 128.6, 129.2, 134.2, 142.1 (Ar-C),
163.6 (C5), 165.6 (C2), 196.2 (C=O). Anal. Calcd. for
C12H12N2O3S3: C, 43.88; H, 3.68; N, 8.53. Found: C, 43.79; H,
3.72; N, 8.59.
1-(4-Chloro-phenyl)-2-{[(5-sulfanyl-1,3,4-oxadiazol-2-yl)-
methyl]sulfonyl}-1-ethanone (13c). White solid, Yield 0.24 g
(71%), mp 212-214 °C; ir: 1126, 1338 (SO2), 1628 (C=N), 1685
1
(C=O), 2600 (SH) cm-1; H nmr (DMSO-d6): ꢁH 4.69 (s, 2H,
1-(4-Chloro-phenyl)-2-{[(5-sulfanyl-1,3,4-thiadiazol-2-yl)-
methyl]sulfonyl}-1-ethanone (11c). White solid, Yield 0.25 g
(69%), mp 209-211 °C; ir: 1122, 1335 (SO2), 1627 (C=N), 1681
SO2-CH2), 4.77 (s, 2H, CH2-SO2), 7.29-7.58 (m, 4H, Ar-H),
10.30 (s, 1H, SH); 13C nmr (DMSO-d6): ꢁC 55.1 (SO2-CH2), 59.1
(CH2-SO2), 128.8, 130.0, 135.5, 138.2 (Ar-C), 161.3 (C5), 167.2
(C2), 194.4 (C=O). Anal. Calcd. for C11H9ClN2O4S2: C, 39.70; H,
2.73; N, 8.42. Found: C, 39.77; H, 2.69; N, 8.54.
1
(C=O), 2563 (SH) cm-1; H nmr (DMSO-d6): ꢁH 4.70 (s, 2H,
SO2-CH2), 4.73 (s, 2H, CH2-SO2), 7.36-7.79(m, 4H, Ar-H),
10.22 (s, 1H, SH); 13C nmr (DMSO-d6): ꢁC 52.4 (SO2-CH2), 61.3
(CH2-SO2), 128.8, 129.6, 135.4, 138.2 (Ar-C), 159.8 (C5), 167.5
(C2), 197.1 (C=O). Anal. Calcd. for C11H9ClN2O3S3: C, 37.87; H,
2.60; N, 8.03. Found: C, 37.95; H, 2.63; N, 8.07.
Acknowledgements. The authors are thankful to DST, New
Delhi, India for the financial assistance under major research
project.
2-{[(4-Amino-5-sulfanil-4H-1,2,4-triazol-3-yl)methyl]-
sulfonyl}-1-phenyl-1-ethanone (12a). White solid, Yield 0.23 g
(75%), mp 157-159 °C; ir: 1142, 1338 (SO2), 1633(C=N), 1683
(C=O), 2621(SH), 3269 (NH2) cm-1; 1H nmr (DMSO-d6): ꢁH 4.68
(s, 2H, SO2-CH2), 4.79 (s, 2H, CH2-SO2), 5.61 (br s, 2H, NH2),
7.41-7.78 (m, 5H, Ar-H), 10.24 (s, 1H, SH); 13C nmr (DMSO-
d6): ꢁC 43.4 (SO2-CH2), 61.2 (CH2-SO2), 128.4, 128.6, 132.8,
137.4 (Ar-C), 144.1 (C5), 168.1 (C3), 196.4 (C=O); ms: m/z 312
(M+.). Anal. Calcd. for C11H12N4O3S2: C, 42.30; H, 3.87; N,
17.94. Found: C, 42.35; H, 3.92; N, 17.88.
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(DMSO-d6): ꢁH 4.72 (s, 2H, SO2-CH2), 4.78 (s, 2H, CH2-SO2),
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