Expedient and green synthesis of some novel 4-thiazolidinones and new 2,4-disubstituted thiazoles with tetrahydro carbazole pendant

Article abstract of DOI:10.2174/157017812803521081

A green and efficient synthesis of novel 4-thiazolidinones 4 from cyclocondensation reaction of 2-(2,3-dihydro-1H-carbazol-4(9H)-ylidene) hydrazinecarbothioamide 3 and α-haloacids catalyzed by N-methylpyridinium tosylate in quantitative yield is reported. Also, synthesis of new 2,4-disubstituted thiazoles 5 under grinding conditions is reported.

Full text of DOI:10.2174/157017812803521081

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660
Letters in Organic Chemistry, 2012, 9, 660-663
Expedient and Green Synthesis of Some Novel 4-Thiazolidinones and New
2,4-Disubstituted Thiazoles with Tetrahydro Carbazole Pendant
Deepika Gautam, Poonam Gautam and Ram P. Chaudhary*
Department of Chemistry, Sant Longowal Institute of Engineering & Technology, Longowal (Sangrur) Punjab-148106,
India
Received July 06, 2012: Revised August 10, 2012: Accepted September 10, 2012
Abstract: A green and efficient synthesis of novel 4-thiazolidinones 4 from cyclocondensation reaction of 2-(2,3-dihydro-
1H-carbazol-4(9H)-ylidene)hydrazinecarbothioamide 3 and ꢀ-haloacids catalyzed by N-methylpyridinium tosylate in
quantitative yield is reported. Also, synthesis of new 2,4-disubstituted thiazoles 5 under grinding conditions is reported.
Keywords: 4-Thiazolidinones, N-methylpyridinium tosylate, cyclocondensation, thiazoles, grinding.
INTRODUCTION
RESULTS AND DISCUSSION
The heterocyclic carbazole motif is a privileged pharma-
cophore scaffold found in many biologically active com-
pounds of diverse origins, from natural products to synthetic
sources. Chemists have been attracted to these structures due
to their biological activities and potential applications as
pharmacological activities such as antimicrobial [1] antima-
larial [2], antiseratonin [3], anticonvulsant [4], anti-
inflammatory [5], pancreatic lipase inhibition [6], and anti-
cancer [7], etc. Also, carbazoles have been the subject of
significant study by virtue of their intense luminescence and
structure stability. They are widely used as organic emitters,
and also undergo reversible oxidation processes, which make
them suitable hole carriers [8]. Due to their tunable molecu-
lar and photophysical properties, carbazoles are one of the
important classes of advanced materials, which have been
pursued for applications in organic light-emitting diodes
(OLEDs) [9,10] and other optoelectronic devices [11]. In the
present paper we report the synthesis of some novel 4-
thiazolidinones and thiazoles containing carbazole moiety
from thiosemicarbazone derivative of 2,3-dihydro-1H-
carbazol-4(9H)-one. Various approaches for the synthesis of
4-thiazolidinones are available in the literature [12]. Never-
theless a common synthetic strategy to construct imino thia-
zolidinones is the cyclization of thiosemicarbazide deriva-
tives with ꢀ-halo esters or acids in the presence of inorganic
base (i.e. NaOAc) in polar solvents using either conventional
or microwave irradiation methods [13, 14]. However, most
of the reported procedures suffer from drawbacks of longer
reaction times, use of hazardous solvents and moderate
yields. We have investigated the use of N-methyl-pyridinium
tosylate, an ionic liquid, for the cyclocondensation of
thiosemicarbazide derivative of 2,3-dihydro-1H-car-bazol-
4(9H)-one carbazole with ꢀ-halo acids to yield novel hetero-
cycles 4 and 5 and it was found that reaction occurs in short
time and yield of the products is quantitative.
The synthesis of carbazole derivatives 4 and 5 was per-
formed in a manner as outlined in Scheme-1. 2, 3-Dihydro-
1H-carbazol-4(9H)-one 2 was obtained by the oxidation of
tetrahydrocarbazole 1 with dichlorodicyanobenzoquinone
(DDQ) in aqueous dioxane using known procedure [15].
Compound 2 was characterized by IR, NMR and mass spec-
tral data. The appearance of a peak at 1690 cm-1 in IR and at
1
ꢁ 193 in 13C NMR of 2 is assigned to C=O group. In H
NMR appearance of one multiplet and two triplets at ꢁ 2.18
and ꢁ 2.50, ꢁ 2.97 respectively is due to tetrahydrocarbazole
ring. Compound 2 exhibited molecular ion peak at m/z 186
(M+H)+ (100%). Treatment of compound 2 with thiosemi-
carbazide in the presence of catalytic amount of conc. HCl
afforded carbothioamide 3. The structure of 3 was estab-
lished by elemental analysis and spectral data. Compound 3
on cyclocondensation with chloroacetic acid or 2-
bromopropionic acid in premolten N-Methylpyridinium to-
sylate at 1000 C for 1-2 hrs afforded 4a and 4b in excellent
yields (80-85%). Thiazoles 5a and 5b were obtained from 3
and substituted phenacyl bromides by grinding in a pestle
mortar in a fume cup board in the absence of any solvent for
5-10 minutes at ambient temperature in almost quantitative
yields (88-90%). The characterization of 4 and 5 was done
on the basis of elemental analysis and spectral data. The
elemental analysis data of 4 and 5 is found to be in good
agreement with calculated values (within the range of ±
0.4%). In IR of 4a and 4b appearance of peaks at 1713 cm-1
and 1705 cm-1 respectively is attributed to carbonyl groups.
In 1H NMR spectrum of 4a appearance of a peak at ꢁ 3.75 is
assigned to the SCH2 group of the thiazolidinone ring. The
appearance of a quartet and a doublet at ꢁ 4.03 and ꢁ 1.56
1
respectively in H NMR of 4b is assigned to SCH (CH3)
group of thiazolidinone ring. 4a and 4b exhibited molecular
ion peaks in mass spectrum at m/z 299 (M+H)+ (100%) and
1
m/z 313 (M+H)+ (100%) respectively. In H NMR spectrum
of 5a and 5b the appearance of singlets at ꢁ 7.15 and ꢁ 7.18
is characteristic of =CH of thiazole ring. The conventional
synthesis of 4a and 4b in presence of inorganic base NaOAc
and absolute ethanol required 7-8 hrs refluxing and the prod-
*Address corresponding to this author at the Department of Chemistry, Sant
Longowal Institute of Engineering & Technology, Longowal (Sangrur)
Punjab-148106, India; Tel: 91-1672-253206; Fax: 91-1672-280057;
E-mail: rpchaudhary65@gmail.com
1875-6255/12 $58.00+.00
© 2012 Bentham Science Publishers

Expedient and Green Synthesis of Some Novel 4-Thiazolidinones
Letters in Organic Chemistry, 2012, Vol. 9, No. 9 661
R
H
S
O
S
N
N
Ar
HN
N-Methylpyridinium tosylate
N
H
N
Grinding
N
HN
N
3
H
ArCOCH2Br
ꢀ
4a, R= H
b, R= CH3
5a, Ar= p-Cl-C6H4
b, Ar= p-NO2-C6H4
H2NSCHNN
O
NH2NHCSNH2
DDQ
N
N
H
H
N
H
3
2
1
Scheme 1. Synthesis of 4-thiazolidinones and thiazoles containing carbazole moiety.
Synthesis of 2-(2,3-dihydro-1H-carbazol-4(9H)-ylidene)
hydrazinecarbothioamide (3)
ucts are obtained in low yield (50-55%). The use of ionic
liquid, N-Methyl pyridinium tosylate in reaction of 3 with ꢀ-
halo acids to yield 4a and 4b has an advantage of easy work
up, faster reaction and quantitative yields. Moreover, recov-
ery of the ionic liquid was also attempted at the end of the
reaction and it was found that it can be used for two more
cycles without affecting the yield of the products.
A mixture of 2 (0.346 g, 1.87 mmol) and thiosemicar-
bazide (0.170 g, 1.87 mmol) and 0.4 mL conc. HCl in abso-
lute ethanol (10 mL) was stirred at room temperature for 3
hrs. Poured into ice cold water, the solid thus separated was
filtered, dried and recrystallized from ethanol.
White crystals, yield 81 %, m.p. 185-6 C. IR (cm-1)
0
EXPERIMENTAL
3240, 3178 (NH), 1574 (C=N), 1504 (C=C), 1273 (C=S), 1H
NMR (400 MHz, DMSO-d6) ꢁ 2.18-2.23 (m, 2H, CH2), 2.50-
2.53 (t, 2H, CH2, J= 6.52 Hz), 2.97-3.00 (t, 2H, CH2, J= 6.08
Hz), 7.10-7.18 (m, 2H, ArH), 7.33-7.37 (m, 1H, ArH), 8.05-
8.07 (m, 1H, ArH), 9.59 (br, 1H, NH), 11.00 (br, 1H, NH),
11.38 (br, 1H, NH), Elemental analysis: Calcd for
C13H14N4S, C= 60.46, H= 5.42, N= 21.70, S= 12.40% found
C= 60.42, H= 5.36, N= 21.61, S= 12.28%.
All the chemicals used were obtained from Sigma and
used without further purification. Melting points were de-
termined in open capillaries and were uncorrected. Elemental
analysis was done on a Carlo-Erba 1108 elemental analyzer.
Mass spectra were recorded on a TOF MS ES+ 2.44e4 in-
1
strument. H NMR and 13C NMR were recorded in DMSO-
d6 on a BRUKER AVANCE II 400 NMR spectrometer using
tetramethylsilane (TMS) as an internal standard. The chemi-
cal shifts are reported in ppm. IR spectra were recorded on
ABB FTIR spectrometer and the results are reported in cm-1.
Thin layer chromatography (TLC) was performed on silica
gel G coated plates and using iodine vapor as a visualizing
agent.
Solvent Free General Procedure for Synthesis of 4a and
4b
An equimolar mixture of 3 (0.025 mol) and chloroacetic
acid or 2-bromopropionic acid (0.025 mol) in premolten
0
ionic liquid 2.0 g was stirred at 100 C for 1-2 hrs. The reac-
2,3-Dihydro-1H-carbazol-4(9H)-one (2)
tion was monitored by TLC, poured in ice cold water, fil-
tered the solid obtained, dried and recrystallized from etha-
nol.
Compound 2 was obtained from oxidation of tetrahydro-
carbazole 1 with DDQ by reported procedure [15].
0
White crystals, m.p. 216-18 C (Lit15. m.p. = 219-210C),
yield 62%, IR (cm-1) 1690 (C=O), 1H NMR (400 MHz,
DMSO-d6) ꢁ 2.18-2.23 (m, 2H, CH2), 2.50-2.53 (t, 2H, CH2,
J= 6.24 Hz), 2.97-3.00 (t, 2H, CH2, J= 6.08 Hz), 7.13-7.16
(m, 2H, ArH), 7.35-7.37 (m, 1H, ArH), 8.05- 8.07 (m, 1H,
ArH), 11.40 (br, 1H, NH), 13C NMR (100 MHz, DMSO d6) ꢁ
193.30 (C=O), 135.74, 124.37, 122.16, 121.28, 111.95,
110.99 (ArC), 40.23 (CH2), 37.72 (CH2), 22.86 (CH2); Mass:
m/z 186 (M+H)+ (100%), Elemental analysis: Calcd. for
C12H11NO, C= 77.81, H= 5.99, N= 7.56%, found C= 77.72,
H= 5.87, N= 7.52%.
Conventional Procedure for Synthesis of 4a and 4b
A mixture of 3 (0.625 mmol), chloroacetic acid or 2-
bromopropionic acid (0.625 mmol) and anhydrous sodium
acetate (1.25 mmol) in absolute ethanol (5.0 mL) was re-
fluxed on water bath for 7-8 hrs. The progress of the reaction
was monitored by TLC. The solvent was removed under
reduced pressure. The solid thus obtained was recrystallized
from ethanol.

662 Letters in Organic Chemistry, 2012, Vol. 9, No. 9
Gautam et al.
(Z)-2-((E)-(2,3-dihydro-1H-carbazol-4(9H)-
ylidene)hydrazono)thiazolidin-4-one (4a)
2.17 (m, 2H, CH2), 2.92-2.95 (t, 2H, CH2, J= 5.88 Hz), 2.97-
3.00 (t, 2H, CH2, J= 5.76 Hz), 7.14-7.20 (m, 2H, ArH), 7.32-
7.42 (m, 2H, ArH), 8.01-8.05 (m, 2H, ArH), 8.15-8.17 (m,
1H, ArH), 8.27-8.34 (m, 1H, ArH), 11.35 (br, 1H, NH),
Mass: m/z 404 (M+H)+ (100%), Elemental analysis: Calcd.
for C21H17N5SO2, C= 62.52, H= 4.25, N= 17.36, S= 7.95%
found C= 62.56, H= 4.21, N= 17.30, S= 7.92%.
0
White crystalline powder, yield 85 %, m.p. >250 C. IR
(cm-1) 3364 (NH), 1713 (N-C=O), 1589 (C=N); H NMR
1
(400 MHz, DMSO-d6) ꢀ 2.03-2.06 (t, 2H, CH2, J= 6.20 Hz),
2.88-2.92 (m, 4H, CH2), 3.75 (s, 2H, SCH2), 7.10-7.12 (m,
2H, ArH), 7.31-7.34 (m, 1H, ArH), 8.19-8.21 (m, 1H, ArH),
10.95 (br, 1H, NH), 11.61 (br, 1H, NH), 13C NMR (100
MHz, DMSO d6) ꢀ 176.06 (C=O), 160.05 (C=N), 159.62
(C=N), 135.09, 128.11, 121.23, 119.56, 118.08, 111.01
(ArC), 36.04 (SCH2), 31.07 (CH2), 25.05 (CH2), 23.06 (CH2)
Mass: m/z 299 (M+H)+ (100%), Elemental analysis: Calcd.
for C15H14N4SO C= 60.40, H= 4.69, N= 18.79, S= 10.73%
found C= 60.28, H= 4.65, N= 18.68, S= 10.68%.
CONFLICT OF INTEREST
The author(s) confirm that this article content has no con-
flicts of interest.
ACKNOWLEDGEMENTS
The facilities provided by authorities of Sant Longowal
Institute of Engineering and Technology, Longowal are
gratefully acknowledged.
(Z)-2-((E)-(2,3-dihydro-1H-carbazol-4(9H)-
ylidene)hydrazono)-5-methylthiazolidin-4-one (4b)
Light yellow crystals, yield 83 %,m.p. 232-34 0C. IR (cm-
1
1) 3286 (NH), 1705 (N-C=O), 1612 (C=N); H NMR (400
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Expedient and Green Synthesis of Some Novel 4-Thiazolidinones
Letters in Organic Chemistry, 2012, Vol. 9, No. 9 663
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