Solvent-free one-pot synthesis, characterization, antibacterial and antifungal activities of novel spiropiperidinyl-1,2,4-triazolidine-3-thiones

Article abstract of DOI:10.1007/s10593-011-0720-5

A novel approach towards the synthesis of spiropiperidinyl 1,2,4-triazolidine-3-thiones was proposed, exploiting microwave activation coupled with solvent-free reaction conditions. In search for new leads towards potent antimicrobial agents, we tested all the synthesized compounds for their in vitro antibacterial activity against Bacillus subtilis and Micrococcus luteus and antifungal activity against Aspergillus niger, Candida albicans, Candida-6, and Candida-51. Two of the compounds exerted strong in vitro antibacterial activity against B. subtilis and M. luteus, and all the synthesized compounds were potent against the tested fungal strains.

Full text of DOI:10.1007/s10593-011-0720-5

Chemistry of Heterocyclic Compounds, Vol. 47, No. 1, April, 2011 (Russian Original Vol. 47, No. 1, January, 2011)
SOLVENT-FREE ONE-POT SYNTHESIS, CHARACTERIZATION,
ANTIBACTERIAL AND ANTIFUNGAL ACTIVITIES OF NOVEL
SPIROPIPERIDINYL-1,2,4-TRIAZOLIDINE-3-THIONES
V. Kanagarajan1, J. Thanusu1, M. R. Ezhilarasi1, and M. Gopalakrishnan1*
A novel approach towards the synthesis of spiropiperidinyl 1,2,4-triazolidine-3-thiones was proposed,
exploiting microwave activation coupled with solvent-free reaction conditions. In search for new leads
towards potent antimicrobial agents, we tested all the synthesized compounds for their in vitro
antibacterial activity against Bacillus subtilis and Micrococcus luteus and antifungal activity against
Aspergillus niger, Candida albicans, Candida-6, and Candida-51. Two of the compounds exerted strong
in vitro antibacterial activity against B. subtilis and M. luteus, and all the synthesized compounds were
potent against the tested fungal strains.
Keywords: m-chloro-perbenzoic acid, spiropiperidinyl-1,2,4-triazolidine-3-thiones, antibacterial activity,
antifungal activity, one-pot synthesis.
1,2,4-Triazolidine-3-thiones have normally been obtained from ketone thiosemicarbazones by oxidative
cyclization. Earlier, MnO2 [1, 2], FeCl3·6H2O [1, 3, 4], H2O2 [5], and m-chloroperbenzoic acid [6] had been used
for synthesizing 1,2,4-triazolidine-4-thiones from steroidal and nonsteroidal homocyclic ketone thiosemi-
carbazones. The synthetic pathways of 1,2,4-triazolidine-3-thione derivatives represent an interesting topic since
this 1,2,4-triazole nucleus has been incorporated in a wide variety of therapeutically interesting drugs [7-10]
including H1/H2 histamine receptor blockers, cholinesterase-active agents, CNS stimulants, anxiolytics,
sedatives, analgesics, and anticonvulsants. Some examples of 1,2,4-triazole-based drugs are Estazolam [11],
Alprazolam [12], and Rizatriptan [13].
Bioactive heterocyclic ring systems having the 2,6-diarylpiperidin-4-one nucleus with different substituents
at the C-3 and C-5 positions of the ring have aroused great interest due to their biological properties, such as antiviral,
antitumor [14, 15], CNS stimulant and depressant [16], local anesthetic [17], anticancer [18], and antimicrobial
activity [19], and the piperidines derived from them are also biologically important and act as neurokinin receptor
antagonists [20], analgesic, and antihypertensive agents [21].
Microwave (MW) irradiation has been widely exploited in the last decades to carry out an impressive
number of organic syntheses, benefiting from the dielectric heating in terms of reduced reaction times and
_______
* To whom correspondence should be addressed, e-mail: profmgk@yahoo.co.in.
1Synthetic Organic Chemistry Laboratory, Department of Chemistry, Annamalai University, Annamalainagar-
608 002, Tamil Nadu, India.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 81-89, January 2011. Original
article received July 12, 2008, revised version submitted July 22, 2010.
60
0009-3122/11/4701-0060©2011 Springer Science+Business Media, Inc.

increased yields, especially when coupled with solvent-free techniques. Generally, three types of solvent-free
procedures can be coupled with dielectric heating provided by a microwave source: reactions among neat
reagents, reactions among supported reagents on mineral solid supports, and phase-transfer catalysis reactions.
The neat reagents procedure is doubtlessly the most pursued one due, above all, to its easy work-up and
negligible use of solvents for purification/separation stages. One of the most fertile applications in this field, also
known as Microwave Assisted Organic Synthesis (MAOS) technique, is heterocyclic chemistry, as reported in a
recent review [22].
Silica gel-supported sodium hydrogen sulfate (NaHSO4·SiO2), a nontoxic and inexpensive catalyst, has
been used for one-pot conversion of ketones to amides [23], synthesis of imines [24], single-step synthesis of
4(3H)-quinazolinones [25], and one-pot synthesis of 1,2,3-selenadiazoles [26].
Owing to our interest in synthesizing compounds of therapeutic and pharmacological importance in
solid-state reactions [27, 28], we now present the use of NaHSO4·SiO2 as a heterogeneous catalyst for one-pot
conversion of 2,6-diaryl-3,3-dimethylpiperidin-4-ones 1-5 to 6,6-dimethyl-7,9-diphenyl-1,2,4,8-tetraazaspiro-
[4.5]decane-3-thiones 11-15 in solvent-free media under microwave irradiation, since coupling of solvent-free
synthesis with microwave activation is one of the novel approaches to eco-friendly chemistry.
1,2,4-Triazolidine-3-thione and its derivatives can be conveniently synthesized from aldehyde/ketone
thiosemicarbazones and also from substituted thiosemicarbazide by cyclization using suitable reagents [29] like
MnO2, FeCl3·6H2O, H2O2, and m-chloroperbenzoic acid. There have been some problems associated with the
above synthesis, such as severe conditions, low to moderate yields, and difficulty of separating the products
from the reaction mixture. Cyclocondensation reaction of the respective ketone, aldehyde, and ammonium
acetate in the ratio of 1:2:1, respectively, afforded the 2,6-diaryl-3,3-dimethylpiperidin-4-ones 1-5 [30]. In the
present procedure, treatment of compounds 1-5, thiosemicarbazide, and m-chloroperbenzoic acid in the ratio of
1:1:2 with a catalytic amount of NaHSO4·SiO2 in solvent-free media under MW irradiation affords the
corresponding 7,9-diaryl-6,6-dimethyl-1,2,4,8-tetraazaspiro[4.5]decane-3-thiones 11-15 (Scheme 1) in high yields
with shorter reaction times than the classical method (Table 1). NaHSO4·SiO2 catalyst was shown to be one of the
Scheme 1
S
H
N
S
O
H2N
N
Me
Me
H2N
Me
N
NH2
Me
4
1
5
6
3
H
2
EtOH, reflux, 2h
N
H
N
H
R
R
R
R
6–10
1–5
S
m-CPBA
NaHSO4·SiO2
m-CPBA
CH2Cl2
0–5oC
45–70 min
H2N
N
NH2
MW, 320 W
.
H
3–5 min
S
H
S
H
N
2 N
3
N
H2N
HN4
Me
Me
1NH
Me
5
10
9
6
Me
7
8
N
H
N
H
R
R
R
R
11–15
1, 6, 11 R = H; 2, 7, 12 R = Me; 3, 8, 13 R = OMe; 4, 9, 14 R = F; 5, 10, 15 R = Cl
61

TABLE 1. Physical and analytical data of compounds 11-15
Found, %
+·
m/z [M]
——————
Calculated, %
Com-
pound
MW
MW
Empirical
formula
mp, °C
time,min* yield, %*
C
H
N
11
12
13
14
15
4 (60)
4 (70)
4 (60)
3 (45)
5 (60)
85 (55)
78 (45)
75 (50)
80 (60)
75 (50)
118-120
108-110
112-114
126-128
121-123
68.10
68.15
6.82
6.86
15.85
15.89
353
C20H24N4S
69.39
69.44
7.36
7.42
14.68
14.72
381
C22H28N4S
64.01
64.05
6.80
6.84
13.54
13.58
413
C22H28N4O2S
61.78
61.83
5.66
5.71
14.38
14.42
389
C20H22F2N4S
56.97
57.01
5.21
5.26
13.25
13.30
421
C20H22Cl2N4S
_______
* The values in parentheses are obtained by the classical reaction method.
most efficient MW absorbers with a very high specificity to MW heating. It was possible to reach a temperature
of 110C after 3 min of irradiation in a domestic oven (320 W). The reaction temperature was measured by
immersing a glass thermometer into the reaction bath immediately after the exposure to MW irradiation. As little
as 100 mg of NaHSO4·SiO2 catalyst to 0.01 mol of substrate is the most acceptable ratio in terms of efficiency
and safety, and the power level of 320 W is the most suitable one. Also, the present solvent-free procedure
eliminates the use of chloroform [6] for the formation of respective 1,2,4-triazolidine-4-thiones. The structure of
the newly synthesized compounds 11-15 was confirmed by melting point, elemental analysis, MS, FT-IR, and
one-dimensional NMR (1H and 13C) data. A free radical microwave-assisted mechanism (Scheme 2) has been
proposed for the conversion of thiosemicarbazones generated in situ from their carbonyl precursors
Scheme 2
O
O
S
S
H
O
Ar
H
H
N
N
N
N
HN
.
H
N
H
O
Me
Me
.
Me
Me
O
1–5
Ar
O
11–15
N
H
N
H
R
R
R
R
to the spiro compounds 11-15. It has been well proven that 2,6-diarylpiperidin-4-one ring preferably adopts a
chair conformation with all its substituents in the equatorial position [31]. Moreover, the equatorial position of
phenyl groups at C(2) and C(6) makes the chair conformation more rigid, thereby preventing interconversion of
one chair conformation into another. During the cyclization, the trigonal carbon is converted into tetrahedral
carbon. Hence in the case of compounds 11-15, two diastereomers are now possible having the HNC=S group
either at the axial or equatorial orientation. In our case, the products were obtained as single diastereomers as
evidenced by proton NMR spectral data. It was suggested [32] that in such cyclizations the heterocyclic ring is
preferably closed in such a way that the HNC=S group becomes equatorially attached to C(5) and, therefore, in a
cis position with respect to 7,9-aryl groups.
62

TABLE 2. In vitro Antibacterial Activity of Compounds 11–15
MIC, μg/ml
Compound
B. subtilis
M. luteus
11
100
6.25
6.25
50
100
12.5
6.25
100
50
12
13
14
15
50
Penicillin
Streptomycin
25
25
12.5
12.5
TABLE 3. In vitro antifungal activity of compounds 11–15
MIC, μg/ml
Compound
A. niger
Candida albicans
Candida-6
Candida-51
11
50
50
50
—*
50
12
—*
25
50
50
13
25
50
50
14
25
6.25
12.5
25
12.5
6.25
25
25
15
12.5
50
12.5
25
Amphotericin-B
_______
* No inhibition at 200 μg/ml.
The novel 7,9-diaryl-6,6-dimethyl-1,2,4,8-tetraazaspiro[4.5]decane-3-thiones 11–15 were tested for their
antibacterial activity (Table 2) in vitro against B. subtilis and M. luteus and for their antifungal activity (Table 3)
in vitro against A. niger, C. albicans, Candida-6, and Candida-51. Both activities were expressed as minimum
inhibitory concentration (MIC) in μg/ml. Penicillin and Streptomycin were used as standards for antibacterial
studies. Amphotericin-B was used as the standard for antifungal studies under analogous conditions. The
spiropiperidinyl-1,2,4-triazolidine-3-thiones 12 and 13 having electron-donating methyl and methoxy groups at
the para position of the phenyl ring exerted strong antibacterial activity against the tested strains. Compounds 12
and 13, which have two methyl substitutents at position 6 of the piperidine ring show excellent antibacterial
activity against B. subtilis with a MIC value of 6.25 µg/ml compared to 8-methyl- or 6,8-dimethyl-substituted
spiropiperidinyl-1,2,4-triazolidine-3-thiones [32], which show activity in the MIC range of 25-100 µg/ml.
Electron-deficient fluoro- and chloro-substituted compounds 14 and 15 showed moderate activity against B.
subtilis with a MIC value of 50 µg/ml. All the synthesized compounds 11-15 showed strong antifungal activity
in vitro against the tested organisms in the MIC range of 6.25-50 µg/ml, whereas the analogous compounds
without two 6-CH3 groups [32] show MIC in the range of 25-200 µg/ml. From the present study, it can be
inferred that the addition of the second methyl group at C-6 of piperidine ring enhances the antibacterial and
antifungal activities.
We have described a rapid and convenient microwave-assisted solvent-free protocol for the formation of
1,2,4-triazolidine-3-thiones using a nontoxic and inexpensive NaHSO4·SiO2 catalyst. The advantages of this
environmentally benign and safe protocol include a simple reaction set-up, high product yields, short reaction
times, and elimination of solvents. A close inspection of the in vitro antibacterial and antifungal activity profile
of the novel spiropiperidinyl-1,2,4-triazolidine-3-thiones with different p-substituents in the phenyl ring show
that methyl- and methoxy-substituted compounds 12 and 13 exert a better antibacterial activity against the tested
bacterial strains while the fluoro- and chloro-substituted compounds 14 and 15 are more active against
63

the tested fungal strains. The mechanism of action of these compounds is not known. Further development of
this group of spiropiperidinyl-1,2,4-triazolidine-3-thiones may lead to compounds with a better pharmacological
profile than standard antibacterial and antifungal drugs.
EXPERIMENTAL
The completeness of reactions and the purity of the products were assessed by TLC. All the reported
melting points were determined in open capillaries and were uncorrected. IR spectra were recorded in KBr
pellets on a Nicolet-Avatar 330 FT-IR spectrophotometer, and noteworthy absorption values alone are listed.
1H and 13C NMR spectra were recorded on a Bruker AMX 400 NMR spectrometer (400 and 100 MHz,
respectively) using DMSO-d6 as solvent and TMS as the internal standard. The ESI + ve MS spectra were recorded
on a Bruker Daltonics LC-MS spectrometer. Satisfactory microanalysis was obtained on Carlo Erba 1106 CHN
analyzer.
A conventional (unmodified) domestic microwave oven equipped with a turntable (LG, MG-395 WA,
230V~50Hz, 760 W) was used for the irradiation.
2,6-Diaryl-3,3-dimethylpiperidin-4-ones 1–5 and their thiosemicarbazones 6–10 were prepared
according to the literature procedure [30].
Typical Procedure for the Synthesis of 6,6-Dimethyl-7,9-diphenyl-1,2,4,8-tetraazaspiro[4.5]de-
cane-3-thione (11). Classical method. A solution of 3,3-dimethyl-2,6-diphenylpiperidin-4-one thiosemi-
carbazone (6) (0.01 mol) in dichloromethane (50 ml) was treated with m-chloroperbenzoic acid (0.02 mol) and
stirred for 1 h at 0-5°C. The reaction mixture was decomposed with an ice-cold NaHCO3 solution. The organic
layer was washed with brine and with excess of water, and dried over anhydrous Na2SO4. After evaporation of
the solvent under reduced pressure, a gummy mass was obtained, which solidified on treatment with petroleum
ether (bp 40-60°C). Final purification of compound 11 was done by column chromatography using silica gel
(100–200 mesh), with ethyl acetate–petroleum ether (3:7) (bp 40–60°C) as eluent.
Microwave method. A mixture containing 3,3-dimethyl-2,6-diphenylpiperidin-4-one (1) (0.01 mol),
thiosemicarbazide (0.01 mol), m-chloroperbenzoic acid (0.02 mol), and NaHSO4·SiO2 (100 mg) was added in an
alumina bath and stirred properly with the aid of a glass rod (10 s) and then irradiated in a microwave oven for
4 min at 320 W (monitored by TLC). After the completion of the reaction, the reaction mixture was extracted
with ethyl acetate (3×5 ml). The catalyst and other solid waste were removed by filtration. The combined
organic layer was washed with water three times and then dried over anhydrous MgSO4. The organic layer was
concentrated in vacuo to furnish the product which was purified by column chromatography using silica gel
(100-200 mesh) with ethyl acetate–petroleum ether, 3:7 (bp 40–60°C) as eluent. IR spectrum, , cm–1: 3424, 3366,
1
3146, 3030, 2971, 2928, 1289, 764, 701. H NMR spectrum, , ppm (J, Hz): 0.94 (3H, s, 6-CH3); 1.15 (3H, s,
6-CH3); 2.16 (1H, m, Ha-10); 2.63 (1H, s, H-8); 3.25 (1H, dd, J10e,10a = 14.5, J10e,9a = 3.9, He-10); 3.66 (1H, s, H-7);
3.80 (1H, m, Ha-9); 7.13 (1H, s, H-1); 7.26–7.58 (10H, m, H Ar); 8.32 (1H, s, H-4). 13C NMR spectrum, , ppm:
20.8 (6-CH3), 21.3 (6-CH3), 32.6 (C-10), 42.4 (C-6), 59.9 (C-9), 69.7 (C-7), 79.1 (C-5), 126.7 (p-C Ar), 127.0 (p-C
Ar), 127.1 (o-, m-C Ar), 127.3 (o-C Ar), 127.9 (m-C Ar), 128.0 (ipso-C Ar), 140.4 (ipso-C Ar), 179.0 (C-3).
Compounds 12–15 were synthesized using both methods above.
6,6-Dimethyl-7,9-bis(4-methylphenyl)-1,2,4,8-tetraazaspiro[4.5]decane-3-thione (12). IR spectrum,
1
, cm–1: 3429, 3315, 3102, 3022, 2972, 2924, 1246, 817, 745. H NMR spectrum, , ppm (J, Hz): 1.02 (3H, s,
6-CH3); 1.08 (3H, s, 6-CH3); 2.07 (6H, s, 2CH3C6H4); 2.22 (1H, m, Ha-10); 2.49 (1H, s, H-8); 3.02 (1H, dd,
J
10e,10a = 14.5, J10e,9a = 3.8, He-10); 3.61 (1H, s, H-7); 3.69 (1H, m, Ha-9); 7.08 (1H, s, H-1); 7.10–7.42 (8H, m,
13
H Ar); 8.50 (1H, s, H-4). C NMR spectrum, , ppm: 20.6 (6-CH3), 21.1 (6-CH3), 22.7 (CH3C6H4), 32.3 (C-10),
42.2 (C-6), 59.8 (C-9), 69.5 (C-7), 79.0 (C-5), 126.5 (o-C Ar), 127.9 (m-C Ar), 128.6 (m-C Ar), 128.7 (o-C Ar),
136.1 (p-C Ar), 137.5 (p-C Ar), 141.1 (ipso-C Ar), 180.0 (C-3).
64

7,9-Bis(4-methoxyphenyl)-6,6-dimethyl-1,2,4,8-tetraazaspiro[4.5]decane-3-thione (13). IR spectrum,
1
, cm–1: 3427, 3314, 3246, 3158, 2969, 2929, 1246, 832, 750. H NMR spectrum, , ppm (J, Hz): 0.92 (3H, s,
6-CH3); 1.16 (3H, s, 6-CH3); 2.22 (1H, m, Ha-10); 2.49 (1H, s, H-8); 3.49 (1H, dd, J10e,10a = 14.3, J10e,9a = 3.6,
He-10); 3.59 (1H, s, H-7); 3.71 (1H, m, Ha-9); 3.87 (6H, s, 2OCH3); 7.13 (1H, s, H-1); 7.33-7.97 (8H, m, H Ar);
13
8.30 (1H, s, H-4). C NMR spectrum, , ppm: 20.8 (6-CH3), 22.7 (6-CH3), 32.7 (C-10), 42.6 (C-6), 55.0, 54.9
(OCH3), 59.7 (C-9), 69.1 (C-7), 79.0 (C-5), 126.7 (m-C Ar), 127.8 (m-C Ar), 128.7 (o-C Ar), 129.8 (o-C Ar), 132.5
(ipso-C Ar), 136.2 (ipso-C Ar), 158.4 (p-C Ar), 159.9 (p-C Ar), 179.0 (C-3).
7,9-Bis(4-fluorophenyl)-6,6-dimethyl-1,2,4,8-tetraazaspiro[4.5]decane-3-thione (14). IR spectrum,
1
, cm–1: 3427, 3369, 3254, 3149, 2975, 2931, 1291, 823, 748. H NMR spectrum, , ppm (J, Hz): 1.12, (3H, s,
6-CH3); 1.17 (3H, s, 6-CH3); 2.35 (1H, m, Ha-10); 2.60 (1H, s, H-8); 3.55 (1H, dd, J10e,10a = 14.4, J10e,9a = 3.8,
He-10); 3.59 (1H, s, H-7); 3.72 (1H, m, Ha-9); 7.18 (1H, s, H-1); 7.37-7.81 (8H, m, H Ar); 8.37 (1H, s, H-4).
13C NMR spectrum, , ppm: 21.5 (6-CH3), 22.3 (6-CH3), 32.8 (C-10), 42.8 (C-6), 60.1 (C-9), 69.9 (C-7), 80.6
(C-5), 115.8 (m-C Ar), 116.2 (m-C Ar), 127.8 (o-C Ar), 129.3 (o-C Ar), 137.9 (ipso-C Ar), 141.6 (ipso-C Ar),
158.3 (p-C Ar), 158.7 (p-C Ar), 180.2 (C-3).
7,9-Bis(4-chlorophenyl)-6,6-dimethyl-1,2,4,8-tetraazaspiro[4.5]decane-3-thione (15). IR spectrum,
1
, cm–1: 3425, 3368, 3251, 3147, 2972, 2929, 1289, 824, 745. H NMR spectrum, , ppm (J, Hz): 1.16, (3H, s,
6-CH3); 1.19 (3H, s, 6-CH3); 2.61 (1H, s, H-8); 2.34 (1H, m, Ha-10); 3.54 (1H, dd, J10e,10a = 14.8, J10e,9a = 3.6,
He-10); 3.58 (1H, s, H-7); 3.71 (1H, bd, J9a,10e = 16.4, Ha-9); 7.20 (1H, s, H-1); 7.43–7.83 (8H, m, H Ar); 8.39
13
(1H, s, H-4). C NMR spectrum, , ppm: 21.4 (6-CH3), 22.6 (6-CH3), 32.6 (C-10), 42.4 (C-6), 60.8 (C-9), 69.8
(C-7), 80.1 (C-5), 128.08 (m-C Ar), 128.6 (m-C Ar), 129.4 (o-C Ar), 129.8 (o-C Ar), 136.1 (ipso-C Ar), 137.7
(ipso-C Ar), 141.4 (p-C Ar), 141.4 (p-C Ar), 180.0 (C-3).
Microbiology.
Clinically isolated bacterial strains Bacillus subtilis and Micrococcus luteus, and fungal strains
Aspergillus niger, Candida albicans, Candida-6, and Candida-51 were obtained from the Faculty of Medicine,
Annamalai University, Annamalainagar-608 002, Tamil Nadu, India.
In vitro Antibacterial and Antifungal Activity.
The in vitro activities of compounds 11-15 were tested in Sabouraud's, dextrose broth (SDB) (Hi-media,
Mumbai) for fungi and nutrient broth (NB) (Hi-media, Mumbai) for bacteria by twofold serial dilution method
[33]. The respective test compounds were dissolved in dimethyl sulfoxide to obtain 1 mg/ml stock solution.
Seeded broth (broth containing microbial spores) was prepared in NB from 24 h old bacterial cultures on
nutrient agar (Hi-media, Mumbai) at 37 ± 1°C while fungal spores from 1 to 7 days old Sabouraud's, agar (Hi-
media, Mumbai) slant cultures were suspended in SDB. The colony-forming units (cfu) of the seeded broth were
determined by a plating technique and adjusted in the range of 104105 cfu/ml. The final size was 105 cfu/ml for
antibacterial assay and 1.1-1.5·102 cfu/ml for antifungal assay. Testing was performed at pH 7.4±0.2 for bacteria
(NB) and at a pH 5.6 for fungi (SDB). Exactly 0.4 ml of the solution of test compound was added to 1.6 ml of
seeded broth to form the first dilution. One milliliter of this was diluted with a further 1 ml of seeded broth to
give the second dilution and so on until six such dilutions were obtained. A set of assay tubes containing only
seeded broth was kept as control. The tubes were incubated in BOD incubators at 37±1°C. The minimum
inhibitory concentrations were recorded by visual observations after 24 h of incubation for bacteria and 7296 h
for fungi. Penicillin and Streptomycin were used as the standards for antibacterial studies, and Amphotericin-B
was used as the standard for antifungal studies.
The authors are thankful to the NMR Research Centre, Indian Institute of Science, Bangalore for
recording spectra. One of the authors (V. Kanagarajan) is grateful to the Council of Scientific and Industrial
Research (CSIR), New Delhi, Republic of India for providing financial support in the form of a CSIR-Senior
Research Fellowship in Organic Chemistry. Another author (J. Thanusu) is highly thankful to Annamalai
University authorities for providing financial support in the form of a Research Fellowship.
65

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