A convenient synthesis of 1,3-disubstituted-4-(1′,3′-dithiolane/ dithiane-2′-ylidene)-2-pyrazolin-5-ones

Article abstract of DOI:10.1081/SCC-100105894

1,3-Disubstituted-4-(1′, 3′-dithiolane/dithiane-2′-ylidene)-2-pyrazolin-5-one derivatives like (1a-c), (2a-c), (3a-c) have been obtained by condensation of 2-pyrazolin-5-ones (1), (2) and (3) with carbon disulfide in presence of triethylamine followed by the reaction with 1,2-dibromoethane (4a), 1,3-dibromopropane (4b) and 1,3-dibromobutane (4c) respectively.

Full text of DOI:10.1081/SCC-100105894

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A CONVENIENT SYNTHESIS OF 1,3-DISUBSTITUTED-4-
(1′,3′-DITHIOLANE/DITHIANE-2′-YLIDENE)-2-
PYRAZOLIN-5-ONES
V. K. Ahluwalia a & Suman Dudeja
a Department of Chemistry , University of Delhi , Delhi, 110007, India
Published online: 16 Aug 2006.
To cite this article: V. K. Ahluwalia & Suman Dudeja (2001) A CONVENIENT SYNTHESIS OF 1,3-DISUBSTITUTED-4-(1′,3′-
DITHIOLANE/DITHIANE-2′-YLIDENE)-2-PYRAZOLIN-5-ONES, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 31:20, 3175-3181, DOI: 10.1081/SCC-100105894
To link to this article: http://dx.doi.org/10.1081/SCC-100105894
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SYNTHETIC COMMUNICATIONS, 31(20), 3175–3181 (2001)
A CONVENIENT SYNTHESIS OF
1,3-DISUBSTITUTED-4-(10,30-DITHIOLANE/
DITHIANE-20-YLIDENE)-2-PYRAZOLIN-5-
ONES
V. K. Ahluwalia and Suman Dudeja*
Department of Chemistry, University of Delhi,
Delhi 110 007, India
ABSTRACT
1,3-Disubstituted-4-(10,30-dithiolane/dithiane-20-ylidene)-2-
pyrazolin-5-one derivatives like (1a–c), (2a–c), (3a–c) have
been obtained by condensation of 2-pyrazolin-5-ones (1),
(2) and (3) with carbon disulfide in presence of triethylamine
followed by the reaction with 1,2-dibromoethane (4a), 1,3-di-
bromopropane (4b) and 1,3-dibromobutane (4c) respectively.
The formation of ketene dithioacetals by the condensation of com-
pounds containing active methylene groups with carbon disulfide and alkyl
halides is very well documented.1 Various types of physiological activities,
viz., fungicidal and pesticidal have been associated with 2-pyrazolin-5-
*Corresponding author. Current address: 2682 Shadipur Bazaar, opp. West Patel
Nagar, New Delhi 110 008, India.
3175
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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AHLUWALIA AND DUDEJA
ones2,3 as well as 1,3-dithiane/1,3-dithiolane derivatives.4-6 These in combi-
nation are also reported to exhibit fungicidal activity.7
Earlier methods for the synthesis of the title compounds required
strong bases like methanolic potassium hydroxide7 or n-butyllithium8 and
these required longer time and inert atmosphere. Recently the synthesis of
5-(1,3-dithiolan-2-ylidene)-barbiturate has been reported9a by using modifi-
cation of method of Huang and Cheng9b under similar experimental
conditions.
In this paper, we report the synthesis of title compounds by one pot
method involving reaction of 2-pyrazolin-5-ones with carbon disulfide in
presence of triethylamine and dimethyl sulfoxide (DMSO) followed by the
reaction of the formed salts of dithioacids with dihalides, viz., 1,2-dibro-
moethane (4a), 1,3-dibromopropane (4b) and 1,3-dibromobutane (4c)
(Scheme 1).
This method has the advantage over earlier methods in manipulative
convenience and milder basic conditions, the reaction completing in much
Scheme 1.

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2-PYRAZOLIN-5-ONES
3177
shorter time with improved yields. Use of the dipolar aprotic solvents
like DMSO has the additional advantage to carry out the polar reaction
by stabilizing and increasing the neucleophillic ability of the salt of bis-
hydrodithioylidene derivatives. Thus, the reaction of 3-methyl-1-phenyl-2-
pyrazolin-5-one (1) with carbon disulfide in presence of triethylamine as the
base and using DMSO as the solvent followed by the reaction with 1,
2-dibromoethane (4a) resulted in 3-methyl-1-phenyl-4-(10,30-di-thiane-20-yli-
dene)-2-pyrazolin-5-one (1a) with good yields of 89%. Use of 1,3-diphenyl-
2-pyrazolin-5-one (2) or 1-phenyl-3-propyl-2-pyrazolin-5-one (3) afforded
the corresponding 4-(10,30-dithiane-20-ylidene)-2-pyrazolin-5-ones (1b),
(2b), (3b) and 4-(40-methyl-10, 30-dithiane-20-ylidene)-2-pyrazolin-5-one
(1c), (2c), (3c), respectively, with higher yields as much as 79–89%.
The structures of all these compounds (1a–c), (2a–c) and (3a–c) were
1
assigned on the basis of the microanalysis, H NMR, IR, UV and Mass
spectral data. The starting compounds 2-pyrazolin-5-ones (1–3) were
obtained by the Knorr’s condensation10, 11 of b-ketoester viz., ethyl acet-
oacetate, ethyl benzoylacetate and ethyl butylacetate with phenylhydrazine.
The Knorr’s condensation under microwave irradiation gave 90% yield
compared to 75–80% yield in the earlier methods.7,8,10 This method has
an additional advantage of carrying out the reaction in 8–10 minutes com-
pared to 2 h in the conventional methods.10 One of the pyrazolones (1) has
been prepared earlier by the microwave irradiation method.12
EXPERIMENTAL
Melting points are uncorrected. IR spectra were recorded on a
Shimadzu infrared spectrophotometer IR-435 (vmax in cmÀ1). 1H NMR
spectra were recorded in CDCl3 and CDCl3 þ TFA on a Perkin Elmer R-
32 (90 MHz) spectrometer using TMS as internal standard (Chemical shifts
in ꢀ, ppm). UV spectra were recorded on a Beckman DU-64 spectrophot-
ometer.
3-Methyl-1-phenyl-2-pyrazolin-5-one (1): It has been prepared as
reported earlier.12
1,3-Diphenyl-2-pyrazolin-5-one (2): Ethyl benzoylacetate (3.8 g,
19 mmol) and phenylhydrazine (2.15 g, 19 mmol) were mixed in a conical
flask (50 ml). The mixture was irradiated in a microwave oven for 9 min.
After cooling it, 10-ml ether was added to a yellowish brown viscous mass.
After scratching it vigorously, a white solid separated out. The white solid
was recrytallised in ethanol. A yield of 4.4 g, (94%), m.p.: 137–138ꢀC (lit.13
m.p: 137–137.5ꢀC) was obtained.

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AHLUWALIA AND DUDEJA
Table 1. Spectral Data of Compounds (1a–c)
UV(ꢁmax
[nm]
)
IR(Nujol)
cmÀ1
1H NMR [CDCl3/TMS]
Compd. R1 R2
n
1
[d/ppm]
1a
1b
1c
CH3
CH3
CH3
H
H
H
256, 288 (Sh.) 1680[C ¼ O] 2.4 [s, 3H, CH3]
327, 400 (Sh.) 1600[C ¼ N] 3.5 [s, 4H, 2x-S-CH2-]
1540[C ¼ C] 6.9–8.3 [m, 5H, Ar-H]
1420, 1405,
1270, 1230,
1145[C-H]
2
2
251, 288 (Sh.) 1680[C ¼ O] 1.91–2.28 [m, 2H,-CH2-CH2-CH2],
346, 411 (Sh.) 1600[C ¼ N] 2.45 [s, 3H, C(3)-CH3],
1540[C ¼ C] 3.00 [t, 4H,-S-CH2-CH2-CH2-S]
1420, 1425, 7.00–8.20 [m, 5H, Ar-H]
1405, 1230,
1145[C-H]
255, 294 (Sh.) 1680[C ¼ O] 1.40 [d, 3H,-S-CH(CH3)-CH2-CH2-S],
344, 421 (Sh.) 1600[C ¼ N] 1.61 [q, 2H,-S-CH(CH3)-CH2-CH2-S],
1540[C ¼ C] 2.36 [s, 3H, C(3)-CH3], 3.61–3.82
1470, 1425, [m, 3H, -S-CH(CH3)-CH2-CH2-S-],
1405, 1230, 6.61–8.21 [m, 5H, Ar-H]
1145[C-H]
Table 2. Spectral Data of Compounds (2a–c)
UV(ꢁmax
[nm]
)
IR(Nujol)
cmÀ1
1H NMR [CDCl3/TMS]
Compd.
2a
R1
R2
H
n
1
[d/ppm]
C6H5
263, 309 (Sh.) 1685[C ¼ O]
335, 425 (Sh.) 1600[C ¼ N]
1540[C ¼ C]
3.53 [s, 4H, 2x-S-CH2-]
7.1–8.2 [m, 10H, Ar-H]
1425, 1405, 1285,
1145[C-H]
262, 305 (Sh.) 1685[C ¼ O]
355, 427 (Sh.) 1600[C ¼ N]
1540[C ¼ C]
2b
2c
C6H5
H
2
2
2.20 [m, 2H, -S-CH2
-CH2-CH2-S-]
2.95 [t, 4H, -S-CH2
1425, 1405, 1290, -CH2-CH2-S]
1145[C-H]
265, 310 (Sh.) 1685[C ¼ O]
356, 429 (Sh.) 1600[C ¼ N]
1540[C ¼ C]
7.00–8.35 [m, 10H, Ar-H]
1.40 [d, 3H, -S-CH(CH3)
-CH2-CH2-S-],
C6H5 CH3
1.61–2.1 [q, 2H-S-CH(CH3)
1425, 1470, 1290, -CH2-CH2-S],
1155[C-H]
2.7–3.2 [m, 3H, -S-CH(CH3)
-CH2-CH2-S-],
7.0–8.2 [m,10H, Ar-H]

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2-PYRAZOLIN-5-ONES
Table 3. Spectral Data of Compounds (3a–c)
3179
UV(ꢁmax
[nm]
)
IR(Nujol)
cmÀ1
1H NMR[CDCl3/TMS]
Compd.
3a
R1
R2
H
n
1
[d/ppm]
C3H7
254, 237 (Sh.) 3050, 2850, 1.01[t, 3H, -CH2-CH2-CH3]
328, 400(Sh.) 2950[C-H] 1.63[m, 2H, -CH2-CH2-CH3]
1660[C ¼ O] 3.0[t, 2H, -CH2-CH2-CH3]
1600[C ¼ N] 3.88[s, 4H, 2x-S-CH2]
1540[C ¼ C] 7.55[m, 5H, Ar-H]
1475, 1425,
1410, 1270,
1145[C-H]
3b
C3H7
H
2
251, 286(Sh.) 3050, 2850, 1.01*[t,3H,-CH2-CH2-CH3]
324, 411(Sh.) 2950[C-H]
1.45–1.98[m, 4H, -CH2-CH2-CH3
1660[C ¼ O] and S-CH2-CH2-CH2-S]
1600[C ¼ N] 2.91–3.33[t, 4H,
1540[C ¼ C] -S-CH2-CH2CH2-S]
1470, 1420, 7.10–8.21[m, 5H, Ar-H]
1415, 1270,
1145[C-H]
256, 290(Sh.) 3050, 2850, 1.01[t, 3H, -CH2-CH2-CH3]
3c
C3H7 CH3
2
342, 417(Sh.) 2950[C-H]
1.40[d, 3H, -S-CH(CH3)
1660[C ¼ O] -CH2-CH2-S-],
1600[C ¼ N] 2.15–2.55[m, 4H, -S-CH
1540[C ¼ C] (CH3)-CH2-CH2-S-
1470,1420, and–CH2-CH2-CH3],
1410, 1270, 2.77[t, 2H, -CH2-CH2-CH3]
1145[C-H]
2.94–3.65[m, 3H, -S-CH
(CH3)-CH2-CH2-S-],
6.85–8.15[m, 5H, Ar-H]
*CDCl3/TFA/TMS.
1-Phenyl-3-propyl-2-pyrazolin-5-one (3): Ethyl butyrylacetate (5.1 g,
32 mmol) and phenylhydrazine (3.5 g, 32 mmol) were mixed in a conical
flask (50 ml). The mixture was placed in a microwave oven. After 8 min,
reaction was complete as checked by TLC. After cooling it, 20-ml ether was
added to a viscous mass. The white solid separated out after scratching it
vigorously. This white solid recrystallised by ethanol to obtain 3 as a white
crystalline compound. A yield of 5.9 g, (90.5%), m.p.: 110–111ꢀC (lit14 m.p.:
110–110.5ꢀC) was obtained.
General Procedure: 1,3-Disubstituted-4-(10,30-dithiane-20ylidene)-2-pyr-
azolin-5-ones (1a), (2a) and (3a): 3-Methyl-1-phenyl-2-pyrazolin-5-one
(1, 0.174 g, 1 mmol) was stirred in DMSO (4 ml) for 3–4 min. To this were
added a well stirred solution of triethylamine (0.2 g, 2 mmol) and carbon
disulfide (0.76 g, 1 mmol) in succession with the gap of 3 min. The mixture

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3180
AHLUWALIA AND DUDEJA
was stirred for another 30 min at room temp. With a colour change in the
solution, 1,2-dibromoethane (4a, 0.18 g, 1 mmol) was added. The stirring
was continued for another 2 h at room temperature and completion of the
reaction was checked by TLC. The reaction mixture was poured into ice
water (20 ml) and kept for 1 h. The solid product was collected by filtration,
washed several times with water and dried. It was crystallized by ethanol as
yellow crystals of 1a. A yield of 0.245 g (89.7%), m.p.: 152–153ꢀC (lit.8 m.p.:
162–163ꢀC) was obtained. Similarly 2a and 3a were prepared by using
appropriate 2-pyrazolin-5-ones (2 and 3). The characterization data of the
compounds prepared are given in Table 1.
General Procedure: 1,3-Disubstituted-4-(10,30-dithiane-20-ylidene)-2-pyr-
azolin-5-ones (1b), (2b) and (3b): Compound 1b was obtained under similar
conditions as in the preparation of 1a by condensation of 1 with 1,3-di-
bromopropane (0.2 g, 1 mmol) in the presence of triethylamine and
DMSO. The yield obtained was 0.260 g (89.6%), m.p. 164–165ꢀC (lit.8
m.p. 164–165ꢀC). Similarly 2b and 3b were obtained by using appropriate
2-pyrazolin-5-ones (2 and 3). The characterization data of the compounds
prepared are given in Table 2.
General Procedure: 1,3-Disubstituted-4-(40-methyl-10,30-dithiane-20-yli-
dene)-2-pyrazolin-5-ones (1c), (2c) and (3c): Condensation of 1 (0.174 g,
1 mmol) with carbon disulfide in presence of triethylamine was followed
by treatment with 1,3-dibromobutane (0.21 g, 1 mmol) in a similar manner
as in 1a gave 1c as a yellow solid. The yield obtained was 0.265 g (87.2%)
Table 4. Physical and Analytical Data of Compounds (1a–c), (2a–c) and (3a–c)
Yield
(%)
Time
(hrs)
m.p.
(ꢀC)
Molecular formula(a)
(Mol. Wt.)
Compd.#
1.
R1
R2
n
a
CH3
CH3
H
H
1
2
2
1
2
2
1
2
2
89.7
89.6
87.2
88.7
86.6
81.9
80.5
81.7
79.8
3.5
3.0
3.0
2.0
2.0
2.5
2.5
2.5
3.0
152–153
164–165
173–174
205–206
241–242
275–276
128–129
133-134
141–142
C13H12N2OS2 (276)
C14H14N2OS2 (290)
C15H16N2OS2 (304)
C18H14N2OS2 (338)
C19H16N2OS2 (352)
C20H18N2OS2 (366)
C15H16N2OS2 (304)
C16H18N2OS2 (318)
C17H20N2OS2 (332)
b
c
CH3
CH3
H
2.
3.
a*
b
C6H5
C6H5
C6H5
C3H7
C3H7
C3H7
H
c
CH3
H
a
b**
c
H
CH3
(a) Microanalysis was found to be in agreement with expected values.
*MS (m/z) : 338 (M), **:MS (m/z) : 318 (M+).
#: Crystallized from 1a, 1b: ethanol; 1c: Ethanol-chloroform; 2a, 2b: benzene; 2c:
benzene-petroleum ether; 3a: t-butyl alcohol; 3b: t-butanol-chloroform; 3c:
Petroleum ether-chloroform.

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2-PYRAZOLIN-5-ONES
3181
m.p. 173–174ꢀC. Similarly 2c and 3c were obtained by using appropriate 2-
pyrazolin-5-ones (2 and 3). The characterization data of the compounds
prepared are given in Table 3. Physical and analytical data of all compounds
prepared are given in Table 4.
ACKNOWLEDGMENT
The authors are thankful to Council of Scientific and Industrial
Research (CSIR), New Delhi, India for the financial help.
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Received in the UK June 12, 2000

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