N-methylpyridinium tosylate catalysed green synthesis, x-ray studies and antimicrobial activities of novel (E)-3-amino-2-(e)-(3, 4-dihydronaphthalen-1(2 H)-Ylidene)hydrazono)thiazolidin-4-ones

Article abstract of DOI:10.1080/10426507.2012.729235

3,4-Dihydro-2H-naphthalen-1-ones 1,on reaction with thiocarbohydrazide, afforded monothiocarbohydrazones 2, which, on condensation with chloroacetic acid in the presence of an ionic liquid and bromotrimethylsilane furnish (E)-3-amino-2-(E)-(3,4-dihydronap

Full text of DOI:10.1080/10426507.2012.729235

This article was downloaded by: [University of Stellenbosch]
On: 08 September 2013, At: 23:35
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the
Related Elements
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gpss20
N-Methylpyridinium Tosylate
Catalysed Green Synthesis, X-
Ray Studies and Antimicrobial
Activities of Novel (E)-3-Amino-2-
(e)-(3, 4-Dihydronaphthalen-1(2H)-
Ylidene)Hydrazono)Thiazolidin-4-Ones
Richa Gupta a & Ram Pal Chaudhary a
a Department of Chemistry , Sant Longowal Institute of Engineering
and Technology Longowal , Sangrur , Punjab , India
Accepted author version posted online: 05 Oct 2012.Published
online: 16 Aug 2013.
To cite this article: Richa Gupta & Ram Pal Chaudhary (2013) N-Methylpyridinium Tosylate Catalysed
Green Synthesis, X-Ray Studies and Antimicrobial Activities of Novel (E)-3-Amino-2-(e)-(3, 4-
Dihydronaphthalen-1(2H)-Ylidene)Hydrazono)Thiazolidin-4-Ones, Phosphorus, Sulfur, and Silicon and
the Related Elements, 188:9, 1296-1304, DOI: 10.1080/10426507.2012.729235
To link to this article: http://dx.doi.org/10.1080/10426507.2012.729235
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Phosphorus, Sulfur, and Silicon, 188:1296–1304, 2013
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2012.729235
N-METHYLPYRIDINIUM TOSYLATE CATALYSED GREEN
SYNTHESIS, X-RAY STUDIES AND ANTIMICROBIAL
ACTIVITIES OF NOVEL (E)-3-AMINO-2-(E)-(3,4-
DIHYDRONAPHTHALEN-1(2H)-
YLIDENE)HYDRAZONO)THIAZOLIDIN-4-ONES
Richa Gupta and Ram Pal Chaudhary
Department of Chemistry, Sant Longowal Institute of Engineering and Technology
Longowal, (Sangrur), Punjab, India
GRAPHICAL ABSTRACT
Abstract 3,4-Dihydro-2H-naphthalen-1-ones 1,on reaction with thiocarbohydrazide, afforded
monothiocarbohydrazones 2, which, on condensation with chloroacetic acid in the presence of
an ionic liquid and bromotrimethylsilane furnish (E)-3-amino-2-(E)-(3,4-dihydronaphthalen-
1-(2H)-ylidene)hydrazono)thiazolidin-4-ones 3 in quantitative yields. Acetyl derivatives 5 were
obtained from 3 with acetic anhydride. Monothiocarbohydrazones 2 on condensation with
benzaldehyde yield azomethines 4. The structure of compounds 2–5 has been established by
1
elemental analysis, IR, H NMR, and mass spectral data. The structure of compound 3a has
been further confirmed by X-ray crystallographic data. The compounds 2–5 were screened for
antimicrobial activity. The thiazolidinones 3a and 3b showed maximum antimicrobial activities.
[Supplementary materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental
files: Additional text, tables, and figures.]
Keywords Monothiocarbohydrazones; 4-thiazolidinones; spectral data; X-ray crystallographic
data
Received 27 June 2012; accepted 9 September 2012.
One of the authors Richa Gupta is thankful to the authorities of Sant Longowal Institute of Engineering
and Technology, Longowal for providing financial assistance. The facilities provided by SLIET authorities are
gratefully acknowledged.
Address correspondence to Ram Pal Chaudhary, Department of Chemistry, Sant Longowal Institute of
Engineering and Technology Longowal (Sangrur) Punjab, 148106, India. E-mail: rpchaudhary65@gmail.com
1296

N-METHYLPYRIDINIUM TOSYLATE CATALYSED GREEN SYNTHESIS
1297
INTRODUCTION
1-Tetralone and its various derivatives have proven utility in the synthesis of numerous
biologically active products and play a major role in medicinal chemistry and development
of pharmaceuticals.1 Levobunolol, a derivative of 5-hydroxy-1-tetralone, is a nonselective
beta-blocker used to treat glaucoma. Thiocarbohydrazones derived from the condensation
of thiocarbohydrazide and aldehydes or ketones, have long been reported in the literature for
their fungicidal2 and anticonvulsant3 properties. 4-Thiazolidinone another biologically ac-
tive class of heterocycles have many interesting activity profiles namely COX-1 inhibitors,4
inhibitors of the bacterial enzyme MurB5 and antihistaminic agents.6 Also 4-thiazolidinones
possess diverse biological activities such as analgesic,7 anti-inflammatory,8 anti-HIV,9 cyto-
toxic,10 anticonvulsant,11 antibacterial,12 antifungal,13 antitumor,14 antipsychotic agents,15
and hypnotics. Several methods for the preparation of 4-thiazolidinones have been re-
ported in the literature. The commonly employed methods involve either a one pot, three-
component cyclocondensation of amines, carbonyls, and mercaptoacetic acid or two- step
synthesis via Schiff base intermediates and their cyclocondensation with mercaptoacetic
acid. The use of carbodiimide was reported16 for synthesis of 4-thiazolidinones in good
yield through one pot cyclocondenation of amines, aldehydes, and mercaptoacetic acid.
The similar one pot condensation was carried out recently in presence of an ionic liquid and
the compounds were obtained in quantitative yields.17 The two-step approach involves haz-
ardous solvents and long reaction time nearly 17–20 h with moderate to poor yields. There
are reports of using various desiccants such as sodium sulfate,18 trimethylorthoformate,
azeotropic distillation, and molecular sieves for removal of water from the reaction mix-
ture. In continuation to our work on synthesis of biologically active 4-thiazolidinones19–21
through environmentally benign reaction conditions and reaction media which replaces
volatile organic solvents, we report here a convenient synthesis of novel (E)-3-amino-2-
(E)-(3, 4-dihydronaphthalen-1(2H)-ylidene)hydrazono)thiazolidin-4-ones by two compo-
nent cyclocondensation of thiocarbohydrazones of 1-tetralone with chloroacetic acid using
an ionic liquid and bromotrimethylsilane in quantitative yield.
RESULTS AND DISCUSSION
1-Tetralone was added while stirring to a solution of thiocarbohydrazide in hot water
containing 1–2 drops of conc. HCl. A white solid started separating from the reaction
mixture within a few minutes of stirring which was purified by passing through a column
using pet ether and ethyl acetate (4:1) as eluent. The pure compound thus obtained was
identified as monothiocarbohydrazone 2a of 1-tetralone on the basis of spectral data. The
appearance of peaks at 1590 and 1280 cm−1 in the IR spectrum of 2a are assigned to C = N
and C = S groups respectively. Two triplets, one multiplet integrating for two protons each
at δ 2.57, 2.77, and 1.95–2.06 respectively in the NMR spectrum are assigned to the three
CH2 groups of tetrahydronaphthalene ring. In 13C NMR spectrum of 2a, a peak at δ 178 is
assigned to C = N group. The structure of 2a is further confirmed by its condensation with
aldehyde to yield azomethine 4a.
2a on cyclocondensation with ClCH2COOH in presence of NaOAc yielded 3a in
1
moderate yield (Scheme 1). The appearance of a singlet at δ 3.78 in H NMR of 3a
is assigned to SCH2 group, which confirms the formation of thiazolidinone ring. The
1
appearance of two triplets and a multiplet due to tetrahydronaphthalene ring in H NMR
supports structure 3a. Appearance of peaks at 1705 cm−1 in IR spectrum and at δ 173.5

1298
R. GUPTA AND R. P. CHAUDHARY
Scheme 1
in 13C NMR spectrum assignable to carbonyl group corroborates with structure 3a. The
appearance of [M+H]+ peak at 275 (25%) in the mass spectrum supports the proposed
structure for 3a. Finally, the structure of 3a was also confirmed by single crystal X-ray
structural data. The ORTEP drawing obtained from crystal structure is shown in Fig. 1.
The crystals for X-ray were grown from ethyl alcohol by slow evaporation process at room
temperature. The structure of compound 4a was established by appearance of a peak at
1612 cm−1 (due to C N group) in IR and a singlet of one proton at δ 7.44 assignable
1
to CH group in H NMR spectrum. Compound 3a on reaction with acetic anhydride
furnishes acetyl derivative 5a supporting the presence of NH2 group in 3a. The structure
of 5a is established by spectral data. The IR of 5a shows a peak at 1668 cm−1 assigned
1
to NHCOCH3 group. In H NMR spectrum besides other peaks, one singlet at δ 2.80 is
due to methyl group. 13C NMR spectrum of 5a shows carbonyl groups of NHCOCH3 and
thiazolidinone ring at δ 178 and 173.5, respectively.
Similarly compounds 2b–5b were obtained and their structures were established by
spectral data.
Figure 1 ORTEP drawing indicating molecular structure and atomic labeling of the compound 3a. (Color figure
available online).

N-METHYLPYRIDINIUM TOSYLATE CATALYSED GREEN SYNTHESIS
Table 1 Effect of catalysts on cyclocondensation of thiocarbohydrazones of 1-tetralone and chloroacetic acid
3a 3b
1299
Entry
Ionic liquid/Catalyst
Time (h)
Yield (%)
Time (h)
Yield (%)
1.
2.
3.
4.
N-methylpyridinium tosylate
6.5
4.0
2.5
6.0
72
78
82
72
6.0
3.5
3.0
5.5
69
75
80
68
N-methylpyridinium tosylate + TMS∗Cl
N-methylpyridinium tosylate + TMSBr
N-methylpyridinium tosylate + TMSI
∗Trimethylsilyl.
The cyclocondensation of 2 with ClCH2COOH to give 3 by a conventional method
resulted a poor yield with long reaction time of 12 h. Because of our interest in developing
environmentally benign method for synthesis of 4-thiazolidinones, the condensation was
investigated in presence of ionic liquid N-methylpyridinium tosylate at 100◦C. The reaction
was complete in 6.5 h (monitored by thin layer chromatography [TLC]) and the yield of
the product was increased from 52% (conventional method) to 72%. With an aim to further
improvement in yield and reduction in reaction time, the reaction was carried out using
trimethylsilyl chloride with ionic liquid and to our surprise it was observed that the reaction
was completed in 4 h and yield of the product was increased to 78%.
A series of experiments were carried out using different amounts of trimethylsilyl
chloride with ionic liquid. It was observed that ionic liquid in combination with trimethylsi-
lyl chloride gave maximum yield when the molar ratio between thiocarbohydrazone,
chloroacetic acid, ionic liquid, and trimethylsilyl chloride was 1:1:4:2. The same con-
densation was further investigated by using ionic liquid in combination with trimethylsilyl
bromide and iodide. It was found that condensation was faster (monitored by TLC) and
yield was maximum with trimethylsilyl bromide in the same molar ratio as in case of
trimethylsilyl chloride. The reaction parameters with different catalysts in combination
with ionic liquid are reported in (Table 1).
CONCLUSIONS
A convenient and efficient two component cyclocondensation using an ionic liquid in
presence of TMSBr for the synthesis of new 4-thiazolidinones is reported. The time required
for cyclocondensation is markedly reduced and yields of the products are quantitative. Some
of the compounds have shown moderate antimicrobial activity.
EXPERIMENTAL SECTION
All the chemicals used were purchased from Sigma Aldrich and used without further
purification. Melting points were recorded on melting point apparatus. TLC was performed
on silica gel G plates using ethyl acetate: pet ether (1:4) as an eluent and I2 vapors as
visualizing agents and column chromatography was performed on silica gel column using
pet ether and ethyl acetate as eluent. IR spectra were recorded on ABB FTIR spectrometer
1
and the results were reported in cm−1. H NMR and 13C NMR spectra were recorded
in CDCl3 on Bruker 300 MHz and Bruker Advance II 400 MHz spectrometers using
tetramethylsilane (TMS) as an internal standard (chemical shift in δ, ppm), mass spectra

1300
R. GUPTA AND R. P. CHAUDHARY
on LCMS/MS spectrometer. The elemental analysis of compounds was performed on a
Carlo Erba-1108 elemental analyzer. X-ray diffraction was performed on X Calibur EOS
OXFORD Diffractometer.
Synthesis of Ionic Liquid, N-Methylpyridinium Tosylate
Pyridine (1.1 mol) was added to a methyl-4-toluene sulfonate (1.0 mol) at 0 ◦C–10 ◦C.
After completion of the addition, the reaction mixture was stirred at room temperature for
1 h. The solid, N-methylpyridinium tosylate, was filtered. The product was then washed
with ethyl acetate to remove unreacted reactants and then dried. The physical parameters
of the ionic liquid are in good agreement with those reported in the literature.22
General Procedure for the Synthesis of Monothiocarbohydrazone of
1-Tetralones (2)
To a solution of thiocarbohydrazide (0.005 mol) in hot water (75 mL) was added
1 to 2 drops of conc. HCl. Then, 1-tetralone (0.005 mol) dissolved in ethanol (20 mL)
was added drop wise with constant stirring. The product began to separate during the
course of addition. The reaction mixture was kept overnight at room temperature. The solid
separated was filtered and washed with aq. ethanol. The product was purified by column
chromatography on silica gel column using pet ether: ethyl acetate (9:1) as the eluent to
give monothiocarbohydrazones 2a and 2b in 85% and 83% yield, respectively.
Monothiocarbohydrazone of 1-tetralone (2a). This compound was obtained as a
white shining solid. mp 228◦C–230 ◦C. IR: 1280 (CS), 1590 (C N), 3405 (NH). 1H NMR
(300 MHz, CDCl3), δ: 1.95–2.06 (m, 2H, CH2); 2.57 (t, 2H, J = 6.6 Hz, CH2); 2.77
(t, 2H, J = 6.3 Hz, CH2); 4.42 (br, 2H, NH2, exchange with D2O); 7.17–8.00 (m, 4H,
C6H5); 8.62 (br, 1H, NH, exchange with D2O); 8.72 (br, 1H, NH, exchange with D2O).
13C NMR (100 MHz, CDCl3), δ: 178.6(C N);147.5, 139.7, 131.6, 128.8, 128.1, 125.9,
124.6 (C6H5); 28.9, 25.6, 21.2 (CH2). C11H14N4S (234), Anal. Calcd. C, 56.40; H, 5.98;
N, 23.93; S, 13.67; Found: C, 56.54; H, 5.86; N, 23.81; S, 13.60.
Monothiocarbohydrazone of 6-methoxy-1-t◦etralone (2b). This compound was
◦
obtained as yellow crystalline solid. mp 218 C–20 C. IR: 1285 (CS), 1595 (CN), 3410
(NH). 1H NMR (400 MHz, CDCl3), δ: 1.87–1.93 (m, 2H, CH2); 2.49 (t, 2H, J = 6.6 Hz,
CH2); 2.68 (t, 2H, J = 6.2 Hz, CH2); 3.75 (s, 3H, OCH3); 6.30 (br, 1H, NH, exchange
with D2O); 6.59 (d, 1H, J = 2.6 Hz, C6H5); 6.70–6.73 (m, 1H, C6H5); 7.19 (br, 1H, NH,
exchange with D2O); 7.28 (br, 1H, NH2, exchange with D2O); 7.85 (d, 1H, J = 8.8 Hz,
C6H5); 8.66 (br, 1H, NH2, exchange with D2O). 13C NMR (100 MHz, CDCl3), δ: 178.3
(C = N); 159.9, 147.8, 141.6, 126.5, 124.4, 112.8, 112.0 (C6H5); 54.8, 29.2, 25.5, 21.3
(CH2). C12H16N4SO (264), Anal. Calcd. C, 54.54; H, 6.06; N, 21.21; S, 12.12; Found: C,
54.62; H, 6.14; N, 21.18; S, 12.20.
Conventional Procedure for Synthesis of (3)
A mixture of compound 2 (0.005 mol), chloroacetic acid (0.47 g, 0.005 mol) and
anhyd. sodium acetate (4.1 g, 0.05 mol) in anhyd. ethanol (20 mL) was heated under reflux
for 12 h. The volume of the reaction mixture was reduced to half and kept overnight. The

N-METHYLPYRIDINIUM TOSYLATE CATALYSED GREEN SYNTHESIS
1301
solid thus separated was filtered, washed well with water and crystallized from ethyl acetate
to give 3a and 3b in 52 and 54% yields, respectively.
Solvent Free General Procedure for Synthesis of (3)
An equimolar mixture of compound 2 (0.005 mol) and chloroacetic acid (0.47 g,
0.005 mol) in premolten ionic liquid (0.02 mol) and trimethylsilyl halides (0.01 mol) was
◦
◦
stirred at 90 C–100 C for 2–6 h (Table 1). The progress of the reaction was monitored
by TLC. The reaction mixture was poured into ice cold water, filtered the solid obtained,
dried and crystallized from ethyl acetate to give 3a and 3b.
(E)-3-Amino-2-(E)-(3,4-dihydronaphthalen-1(2H)-ylidene)hydrazono)thiazoli-
din-4-one (3a). This compound was obtained as creamy shinning crystals. mp
◦
1
128◦C–30 C. IR: 1705 (CO), 1595 (CN). H NMR (300 MHz, CDCl3), δ: 1.90–1.99
(m, 2H, CH2); 2.83 (t, 2H, J = 6.0 Hz, CH2); 2.95 (t, 2H, J = 6.3 Hz, CH2); 3.78 (s,
2H, SCH2); 4.69 (br, 2H, NH2, exchange with D2O); 7.16 (d, 1H, J = 7.5 Hz, C6H5);
7.23–7.35 (m, 2H, C6H5); 8.25 (d, 1H, J = 7.5 Hz, C6H5). 13C NMR (100 MHz, CDCl3),
δ: 173.5 (C O); 162.5 (C N); 162.1 (C N); 140.9, 132.3, 130.1, 128.6, 126.3, 125.5
(C6H5); 33.1 (SCH2); 29.9 (CH2); 27.4 (CH2); 22.2 (CH2). MS, m/z (%): 275 [M+1]+
(25). C13H14N4SO (274), Anal. Calcd. C, 56.93; H, 5.10; N, 20.43; S, 11.67; Found, C,
56.80; H, 5.22; N, 20.38; S, 11.72.
(E)-3-Amino-2-(E)-(6-methoxy-3,4-dihydronaphthalen-1(2H)-ylidene)hydrazo-
no)thiazolidin-4-one (3b). This compound was obtained as light brown crystals. mp
◦
1
184◦C–85 C. IR: 1712 (CO), 1605 (CN). H NMR (400 MHz, CDCl3), δ: 1.84 (t, 1H,
J = 6.4 Hz, CH2); 1.89 (t, 1H, J = 6.4 Hz, CH2); 2.54 (t, 1H, J = 6.4 Hz, CH2), 2.70–2.73
(m, 2H, CH2); 2.81 (t, 1H, J = 6.5 Hz, CH2); 3.76 (s, 2H, SCH2); 3.78 (s, 3H, OCH3);
6.58 (dd, 1H, J = 16.8, 2.4 Hz, C6H5) 6.74 (d, 1H, J = 2.6 Hz, C6H5); 7.96 (t, 1H, J =
8.9 Hz, C6H5); 9.75 (br, 1H, NH2, exchange with D2O); 14.2 (br, 1H, NH2, exchange
with D2O). 13C NMR (100 MHz, CDCl3), δ: 173.5 (C = O); 160.3 (C N); 159.5 (C N);
142.0, 126.5, 125.0, 128.6 (C6H5); 54.9 (OCH3); 32.7 (SCH2); 29.7 (CH2); 26.8 (CH2);
21.8 (CH2). MS, m/z (%): 305 [M+1]+ (30). C14H16N4SO2 (304), Anal. Calcd. C, 55.26;
H, 5.26; N, 18.42; S, 10.52; Found, C, 55.34; H, 5.14; N, 18.52; S, 10.64.
General Procedure for the Synthesis of Compound (4)
A mixture of compound 2 (0.002 mol) and benzaldehyde (0.002 mol) in absolute
ethanol (20 mL) was refluxed for 1 h and kept overnight. The separated solid was filtered and
crystallized from ethanol to give compounds 4a and 4b in 71% and 68% yield, respectively.
Compound (4a). This compound was obtained as white crystals. mp 178◦C–80◦C.
IR: 1612 (CN), 1512 (C C), 1296 (C S). 1H NMR (300 MHz, CDCl3), δ: 2.04 (m, 2H,
CH2); 2.68 (t, 2H, J = 6.9 Hz, CH2); 2.81 (t, 2H, J = 5.4 Hz, CH2); 7.17–8.38 (m, 9H,
C6H5); 7.44 (s, 1H, =CH); 8.94 (br, 1H, NH, exchange with D2O); 10.57 (br, 1H, NH,
exchange with D2O). C18H18N4S (322), Anal. Calcd. C, 67.08; H, 5.59; N, 17.39; S, 9.93;
found, C, 67.14; H, 5.66; N, 17.32; S, 9.86.
Compound (4b). This compound was obtained as white needles. mp 187 ◦C–90 ◦C.
IR: 1610 (CN), 1518 (C C), 1292 (C S). 1H NMR (300 MHz, CDCl3), δ: 2.02 (m, 2H,
CH2); 2.66 (t, 2H, J = 6.6 Hz, CH2); 2.85 (t, 2H, J = 5.6 Hz, CH2); 3.78 (s, 3H, OCH3);
7.17–8.33 (m, 8H, C6H5); 7.40 (s, 1H, = CH); 8.90 (br, 1H, NH, exchange with D2O);

1302
R. GUPTA AND R. P. CHAUDHARY
10.60 (br, 1H, NH, exchange with D2O). C19H20N4S (336), Anal. Calcd. C, 64.77; H, 5.68;
N, 15.90; S, 9.09; found, C, 64.88; H, 5.72; N, 15.81; S, 9.04.
General Procedure for the Synthesis of Compound (5)
To a solution of 3 (0.001 mol) in 10 mL of absolute ethanol 1.0 mL of acetic anhydride
is added. The reaction mixture was refluxed on water bath for 1.0 h. The volume of the
reaction mixture was reduced to half under vacuum and kept overnight. The solid obtained
was filtered and recrystallized from ethanol to furnish compounds 5a and 5b in 72 and 78%
yields respectively.
N-((E)-2-((E)-(3,4-dihydronaphthalen-1(2H)-ylidene)hydrazono)-4-oxothiazol-
◦
1
idin-3-yl)acetamide (5a). mp 168◦C–70 C. IR: 1702 (CO), 1668 (CO), 1590 (CN). H
NMR (300 MHz, CDCl3), δ: 1.92–1.98 (m, 2H, CH2); 2.80 (s, 3H, CH3); 2.85 (t, 2H,
J = 6.2 Hz, CH2); 2.90 (t, 2H, J = 6.5 Hz, CH2); 3.80 (s, 2H, SCH2); 5.24 (br, 1H, NH,
exchange with D2O); 7.20 (d, 1H, J = 7.8 Hz, C6H5); 7.26–7.39 (m, 2H, C6H5); 8.30 (d,
1H, J = 7.4 Hz, C6H5); 13C NMR (75 MHz, CDCl3), δ: 178, 173.5 (C O); 165 (C N);
160.5 (C N); 140.5, 132.7, 132.1, 130.6, 126.5, 125.8 (C6H5); 35.1 (SCH2); 32.9 (CH2);
27.7 (CH2); 22.8 (CH2). MS, m/z (%): 317 [M+1]+ (25). C15H16N4SO2 (316), Anal.
Calcd. C, 56.96; H, 5.06; N, 17.72; S, 10.12; Found: C, 56.87; H, 5.12; N, 17.78; S, 10.17.
N-((E)-2-((E)-(6-methoxy-3,4-dihydronaphthalen-1(2H)-ylidene)hydrazono)-4-
oxothiazolidin-3-yl)acetamide (5b). mp 210 ◦C–12 ◦C. IR: 1715 (CO), 1666 (CO), 1605
1
(CN). H NMR (300 MHz, CDCl3), δ: 1.80–1.88 (m, 2H, CH2); 2.84 (s, 3H, CH3); 2.68
(t, 2H, J = 6.1 Hz, CH2); 2.95 (t, 2H, J = 6.2 Hz, CH2); 3.76 (s, 2H, SCH2); 3.83 (s, 3H,
Table 2 Crystal data and structure refinement of compound 3a
Compound
3a
Empirical formula
C13 H14 N4 O S
Formula weight
274.35
Crystal system/Space group
Monoclinic/P21/n (No. 14)
a/Å
b/Å
c/Å
α/◦
β/◦
γ /◦
V/Å3
Z
13.923(3)
7.973(2)
23.625(8)
90
93.29(3)
90
2618.2(12)
8
Dcalc (g cm−3
μ (mm−1
)
1.392
0.245
)
Crystal size (mm)
Color/Shape
Temp (K)
0.22 × 0.28 × 0.32
Pale Yellow/Block
293
Theta range for collection
Reflections collected
Independent reflections
Data/restraints/parameters
Goodness of fit on F2
Final R indices [I > 2σ(I)]
R indices (all data)
3.05, 29.06
5968
2178
−17: 16; −10: 10; −29: 32
0.969
0.0731
0.1546
Largest difference peak/hole
−0.73/0.56

N-METHYLPYRIDINIUM TOSYLATE CATALYSED GREEN SYNTHESIS
1303
Table 3 Selected geometrical parameters (Å, ◦) of compound 3a
S1–C1
S1–C4
O1–C3
N1–N2
N1–C3
N1–C1
N3–N4
N3–C1
C1–S1–C4
N2–N1–C1
N2–N1–C3
C1–N1–C3
N4–N3–C1
N3–N4–C5
S1–C4–C3
N4–C5–C6
N4–C5–C14
1.759 (5)
1.827 (8)
1.237 (8)
1.394 (7)
1.337 (8)
1.412 (8)
1.417 (7)
1.256 (7)
91.5 (3)
119.4 (5)
122.6 (5)
117.6 (5)
110.8 (5)
114.9 (5)
107.7 (5)
125.1 (6)
116.2 (6)
N4–C5
C3–C4
C5–C14
C7–C8
C8–C9
C9–C14
C5–C6
C6–C7
C6–C5–C14
C5–C6–C7
C6–C7–C8
C7–C8–C9
S1–C1–N3
S1–C1–N1
N1–C1–N3
O1–C3–N1
O1–C3–C4
1.268 (8)
1.489 (10)
1.488 (9)
1.503 (14)
1.498 (10)
1.388 (10)
1.487 (10)
1.510 (10)
118.7 (6)
114.1 (6)
109.6 (7)
112.0 (8)
127.7 (5)
110.4 (4)
121.9 (5)
124.0 (6)
123.2 (6)
OCH3); 7.32–8.26 (m, 4H, C6H5). 13C NMR (75 MHz, CDCl3), δ: 185, 176.2 (C O);
158.2 (C N); 160.7 (C N); 142, 135.2, 129, 128.2, 124.2, 122.6 (C6H5); 34.8 (SCH2);
32 (CH2); 26.6 (CH2); 21.7 (CH2). MS, m/z (%): 347 [M+1]+ (100). C16H18N4SO3 (346),
Anal. Calcd. C, 55.49; H, 5.20; N, 16.18; S, 9.24; Found, C, 55.42; H, 5.26; N, 16.11; S,
9.30.
Crystallographic Study and Structural Description
Compound 3a was crystallized from ethanol by slow evaporation method as shiny
cream crystals. Single crystal X-ray diffraction of 3a has shown that the compound crys-
tallizes in monoclinic system. The crystallographic data CIF file has been deposited with
CCDC. The deposition number is CCDC 824245. The crystallographic data and refinement
parameters of 3a are reported in Table 2. Selected bond lengths and bond angles of 3a are
presented in (Table 3).
Antimicrobial Activities
Antimicrobial activities of compounds 2–5 were studied against a variety of bacterial
stains, such as S. aureus, B. subtilis (gram positive bacteria) and P. aeruginosa (gram
negative bacteria) and fungi like A. niger, C. albicans, and A. fumigatus by the in vitro cup
plate technique using ampicillin trihydrate as positive control and the results are reported
in Table S1 of Supplemental Materials.
REFERENCES
1. Almansa, C.; Gomez, L.A.; Cavalcanti, F.L.; Rodriguez, R.; Garcia-Rafanell, J.; Forn, J. Bioorg.
Med. Chem. Lett. 1995, 5(16), 1833–1838.
2. Arumugam, N.; Raghunathan, R.; Shanmugaiah, V.; Mathivanan, N. Bioorg. Med. Chem. Lett.
2010, 20(12), 3698–3702.

1304
R. GUPTA AND R. P. CHAUDHARY
3. Dimmock, J.R.; Gunda, S.G.R.; Vashishtha, S.C.; Zello, G.A.; Das, U.; Nienaber, K.H.; Stables,
J.P.; Allen, T.M.; Santos, C.L. J. Enzyme Inhib. Med. Chem. 2004, 19(4), 303–312.
4. Eleftheriou, P.; Geronikaki, A.; Hadjipavlou-Litina, D.; Vicini, P.; Filz, O.; Filimonov, D.;
Poroikov, V.; Chaudhaery, S.S.; Roy, K.K.; Saxena, A.K. Eur. J. Med. Chem. 2012, 47, 111–124.
5. Rawal, R.K.; Prabhakar, Y.S.; Katti, S.B.; De-Clercq, E. Bioorg. Med. Chem. 2005, 13,
6771–6776.
6. Firke, S.D.; Firake, B.M.; Chaudhari, R.Y.; Patil, V.R. Asian J. Research Chem. 2009, 2(2),
157–161.
7. Knutsen, L.J.S.; Hobbs, C.J.; Earnshaw, C.G.; Fiumana, A.; Gilbert, J.; Mellor, S.L.; Radford, F.;
Smith, N.J.; Birch, P.J.; Burley, J.R.; Ward, S.D.C.; James, I.F. Bioorg. Med. Chem. Lett. 2007,
17, 662–667.
8. Kumar, A.; Rajput, C.S. Eur. J. Med. Chem. 2009, 44, 83–90.
9. Balzarini, J.; Orzeszko-krzesinska, B.; Maurin, J.K.; Orzeszko, A. Eur. J. Med. Chem. 2009, 44,
303–311.
10. Chandrappa, S.; Prasad, S.B.B.; Vinaya, K.; Kumar, C.S.A.; Thimmegowda, N.R.; Rangappa,
K.S. Invest. New Drugs. 2008, 26, 437–444.
11. Singh, T.; Sharma, P.K.; Mondalc, S.C.; Kumar, N. J. Chem. Pharm. Res. 2011, 3(5), 609–615.
12. Rana, P.B.; Mistry, B.D.; Desai, K.R. ARKIVOC. 2008, xv, 262–279.
13. Ravichandran, V.; Jain, A.; Kumar, K.S.; Rajak, H.; Agrawal, R.K. Chem. Biol. Drug Des. 2011,
78, 464–470.
14. Havrylyuk, D.; Kovach, N.; Zimenkovsky, B.; Vasylenko, O.; Lesyk, R. Arch. Pharm. 2011, 344,
514–522.
15. Barreca, M.L.; Chimirri, A.; Luca, L.D.; Monforte, A.M.; Monforte, P.; Rao, A.; Zappala, M.;
Balzarini, J.; Clercq, E.D.; Pannecouque, C. Bioorg. Med. Chem. Lett. 2001, 11, 1793–1796.
16. Srivastava, T.; Haq, W.; Katti, S.B. Tetrahedron. 2002, 58, 7619–7624.
17. Lingampalle, D.; Jawale, D.; Waghmare, R.; Mane, R. Synth. Commun. 2010, 40, 2397–2401.
18. Sharma, R.C.; Kumar, D. J. Indian Chem. Soc. 2000, 77, 492–493.
19. Gautam, D.; Gautam, P.; Chaudhary, R.P. Heterocycl. Commun. 2011, 17, 147–150.
20. Chaudhary, R.P. Der Pharma Chemica. 2011, 3(3), 288–292.
21. Gupta, R.; Chaudhary, R.P. Phosphorus Sulfur Silicon Relat. Elem. 2012, 187(6), 735–742.
22. Kroutil, J.; Budesinsky, M. Carbohydr. Res. 2007, 342, 147–153.