3-Chloro-2-methylphenyl-substituted semicarbazones: Synthesis and anticonvulsant activity

Article abstract of DOI:10.1016/j.ejmech.2004.03.008

A series of 3-chloro-2-methylphenyl substituted semicarbazones (3-33) was synthesized and evaluated for anticonvulsant and CNS activities. After intraperitoneal injection to mice or rats, the semicarbazone derivatives were examined in the maximal electros

Full text of DOI:10.1016/j.ejmech.2004.03.008

European Journal of Medicinal Chemistry 39 (2004) 729–734
www.elsevier.com/locate/ejmech
Short communication
3-Chloro-2-methylphenyl-substituted semicarbazones:
synthesis and anticonvulsant activity
PerumalYogeeswari a,*, Rathinasabapathy Thirumurugan a, Ramkumar Kavya a, Jayakar
Selwyn Samuel a, James Stables b, Dharmarajan Sriram a
a Medicinal Chemistry Research Laboratory, Pharmacy group, Birla Institute of Technology and Science, Pilani 333031, India
b Preclinical Pharmacology Section, Epilepsy Branch, National Institute of Health, Bethesda, USA
Received 31 October 2003; received in revised form 29 March 2004; accepted 31 March 2004
Available online 11 June 2004
Abstract
A series of 3-chloro-2-methylphenyl substituted semicarbazones (3–33) was synthesized and evaluated for anticonvulsant and CNS
activities. After intraperitoneal injection to mice or rats, the semicarbazone derivatives were examined in the maximal electroshock seizure
(MES), subcutaneous pentylenetetrazole (scPTZ), and subcutaneous strychnine (scSTY)-induced seizure and neurotoxicity screens. The aryl
urea (1) and the semicarbazide (2) showed anticonvulsant activity in the MES and scPTZ screens with acute neurotoxicity, whereas the
semicarbazone derivatives showed good anticonvulsant potency in the scSTY screen with moderate activity against MES and scPTZ screens.
Compound 21 exhibited anticonvulsant potency against all the three screens with lesser neurotoxicity. Some titled compounds exhibited lesser
CNS depression and neurotoxicity compared to phenytoin or carbamazepine as was evident from the CNS studies.
© 2004 Elsevier SAS. All rights reserved.
Keywords: Aryl semicarbazones; 3-Chloro-2-methyl substituted phenyl semicarbazones; Anticonvulsants; CNS depressants
1. Introduction
our recent results with 3-bromo substituted phenyl semicar-
bazones [17] have given an impetus to the present investiga-
tion. In continuation to our work on aryl semicarbazones, the
present work focuses on synthesis and anticonvulsant evalu-
ation of 3-chloro-2-methylphenyl substituted semicarba-
zones, since substitution in the 2-position of the phenyl ring
with electron-donating groups was generally beneficial to
activity as reported elsewhere [18] and the importance of the
ortho-methyl group for anticonvulsant activity had been de-
picted in many studies [19–23] including the recently mar-
keted drug tiagabine.
Epilepsy, one of the most frequent neurological disorders,
is a major public health issue, affecting about 4% of individu-
als over their lifetime [1]. About 20–30% of the patients have
seizures that are resistant to the available medical therapies.
This fact warrants the search for new anticonvulsant drugs.
In recent years, aryl and heteroaryl semicarbazones and
thiosemicarbazones [2–12] have emerged as structurally
novel anticonvulsants. Aryl semicarbazides have also been
reported to display excellent anticonvulsant activity in mice
and rats [13]. In terms of interaction at the binding site, as
proposed previously by Dimmock et al. [14,15], the pharma-
cophoric elements were thought to be a lipophilic aryl ring
and hydrogen bonding semicarbazone moiety. The attach-
ment of a second aryl ring designated as the distal ring to the
proximal aryl ring to increase the van der Waal’s bonding at
the binding site and to increase potency have also been
reported. Substitutions in the aryl ring by halogens have been
found to increase potency in the MES screen [7–10,16] and
2. Chemistry
The synthesis of 3-chloro-2-methyl phenyl semicarba-
zones was accomplished as presented in Scheme 1.
3-Chloro-2-methyl aniline was treated with sodium cyanate
in the presence of glacial acetic acid according to the known
urea preparation method, to yield 3-chloro-2-methyl phenyl
urea (1). The urea derivative (1) on condensation with hydra-
zine hydrate in ethanol in presence of sodium hydroxide gave
the semicarbazide (2). The semicarbazone derivatives (3–33)
were prepared by reaction of the appropriate aryl/alkyl alde-
* Corresponding author. Tel.: +91-1596-244684; fax: +91-1596-244183.
E-mail address: pyogee@bits-pilani.ac.in (P. Yogeeswari).
© 2004 Elsevier SAS. All rights reserved.
doi:10.1016/j.ejmech.2004.03.008

730
P. Yogeeswari et al. / European Journal of Medicinal Chemistry 39 (2004) 729–734
NHCONH2
CH3
NH2
CH3
NaCNO
Glacial
CH3COOH
H2O
Cl
Cl
1
NH2NH2. H2O
EtOH
HCl
Cl
NHCONHNH2
.HCl
CH3
Aldehyde or
Ketone
CH3
CH3COONa
H2O / EtOH
HN OC HN
Cl
N
R
C
2
3-20
Cl
R'
Cl
CH3
CH3
HN OC HN
NHN OC HN
R
N
R
C
21-28
R'
O
N
H
29-33
R
H
R’
H
3
4
5
6
7
H
2-Cl
H
2-OH
H
2-NO2
3-NO2
4-NO2
4-OH
R
R’
CH3
R
H
H
21
22
CH3
CH3
29
30
31
32
33
8
9
H
CH2COCH3
Ph-CH2-
C2H5
Br
Cl
F
H
23 Ph-CH2-
10
11
12
13
14
15
16
17
18
19
20
H
4-CH3
4-OCH3
4-N(CH3)2
3-OCH3, 4-OH
H
24
25
26
CH3
CH3
H
H
i-Butyl
2-furanyl
CH3
H
H
27 CRR’ = Cyclopentylene
28 CRR’ = Cyclohexylene
CH3
CH3
CH3
CH3
CH3
CH3
CH3
2-OH
3-NH2
4-Cl
4-OH
4-NO2
4-NH2
Scheme 1. Synthetic protocol of the title compounds.
hyde or ketone or isatin derivatives with (2). Thin layer
chromatography (TLC) was run throughout the reactions to
optimize the reactions for purity and completion. The physi-
cal and chemical data for the newly synthesized compounds
are presented in Table 1.
ated in the maximal electroshock (MES), subcutaneous pen-
tylenetetrazole (scPTZ), subcutaneous strychnine threshold
test (scSTY) and neurotoxicity screens, using doses of 30,
100 and 300 mg/kg at two different time intervals. These data
are presented in Table 2.Very few compounds were evaluated
orally in rats for activity in MES test at several time points
(Table 3). Some selected compounds were studied for their
CNS behavioral activity in mice using actophotometer and
Porsolt’s swim pool test in rats and the results are presented
in Tables 4 and 5.
3. Pharmacology
The new derivatives (1–33) obtained from the reactional
sequence were injected intraperitoneally into mice and evalu-

P. Yogeeswari et al. / European Journal of Medicinal Chemistry 39 (2004) 729–734
731
Table 1
Physical data of the aryl semicarbazones
Compound
Yield (%)
61
80
75
80
86
84
71
86
53
83
83
79
62
63
37
61
66
54
52
34
57
46
78
74
53
51
75
82
77
41
42
56
71
m.p. (°C)
201
163
193
209
224
211
214
257
239
199
187
216
232
220
215
184
227
191c
265
189
166
251
160
175
144
186
191
182
266
231c
255
271c
267c
Molecular formulaa
C8H9N2OCl
Rf [CHCl3:CH3OH (9:1)]
Log Pb
0.87
0.96
2.53
2.90
2.19
2.83
2.81
2.78
1.88
2.71
1.98
2.17
1.39
2.54
2.15
1.87
2.63
1.84
2.72
2.03
2.03
2.14
2.57
2.34
2.70
2.42
2.30
2.40
1.28
1.68
1.65
1.75
1.35
1
2
3
4
5
6
7
8
0.58
0.53
0.91
0.90
0.74
0.81
0.82
0.85
0.81
0.88
0.92
0.87
0.75
0.92
0.77
0.64
0.90
0.85
0.93
0.83
0.88
0.74
0.90
0.95
0.87
0.89
0.72
0.77
0.78
0.80
0.88
0.69
0.79
C8H10N3OCl
C15H14N3OCl
C15H13N3OCl2
C15H14N3O2Cl
C15H13N4O3Cl
C15H13N4O3Cl
C15H13N4O3Cl
C15H14N3O2Cl
C16H16N3OCl
C16H16N3O2Cl
C17H19N4OCl
C16H16N3O3Cl
C16H16N3OCl
C16H16N3O2Cl
C16H17N4OCl
C16H15N3OCl2
C16H16N3O2Cl
C16H15N4O3Cl
C16H17N4OCl
C11H14N3OCl
C13H16N3O2Cl
C23H22N3OCl
C12H16N3OCl
C14H20N3OCl
C13H12N3O2Cl
C13H16N3OCl
C14H18N3OCl
C16H13N4O2Cl
C16H12N4O2ClBr
C16H12N4O2Cl
C16H12N4O2ClF
C17H15N4O2Cl
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
a Elemental analyses for C, H, N were within 0.4% of the theoretical values.
b Log P was generated using Alchemy 2000 and SciLog P softwares.
c Melting point of the compounds at their decomposition.
4. Results and discussions
6, 21 and 31 showed lesser neurotoxicity. All the other
compounds did not exhibit anticonvulsant activity and neu-
rotoxicity. The acetone semicarbazone derivative (21) exhib-
ited anticonvulsant activity in all the three screens and
emerged as the most active compound in this series.
Some selected compounds were further tested in oral
MES screen using rats at 30 mg/kg (Table 4) in which none of
the compounds showed good protection when compared
with phenytoin. Compound 2 exhibited anti-MES protection
throughout the time period.
In the behavioral study using actophotometer, the com-
pound 4 showed no behavioral despair effect when compared
to phenytoin as represented in Table 4. Compounds 5 and 6
did show decreased locomotor activity in the 30 min interval
but did not show any significant behavior despair effect in 1 h
time period. All other compounds were found to decrease
behavioral activity of the animal. In a similar study using
swim pool test, the immobility time after administration of
the test compounds were compared with carbamazepine
(Table 5). The compounds 8 and 16 were found to show no
Candidate anticonvulsants are often evaluated initially in
the MES and scPTZ screens [24]. The intermediate com-
pounds of the reactional sequence like urea (1) and semicar-
bazide (2) derivatives were also included in the anticonvul-
sant study. The compounds 1 and 2 showed anti-MES
potency better than the semicarbazone derivatives (3–33),
but for a shorter duration (0.5 h). The compounds except 1, 2,
6, 10 and 21 did not show protection in the scPTZ screen. In
the MES screen, the compounds that showed mild protection
at 100 mg/kg include 2, 4, 16, 21 and 32, and in the scPTZ
screen, 5, 6 and 31 (Table 2). Some selected compounds were
also subjected to scSTY threshold test in mice, in which all
the tested compounds showed protection in both time periods
of 0.5 and 4 h. The anti-scSTY activity profile of compounds
4, 5, 6, 8, 16 and 21 were better than the standard drug
ethosuximide. In the acute neurological toxicity screen, the
compounds except 3, 5, 10, 16, 24, 25, 28 and 32 showed
neurotoxicity. When compared with phenytoin, compounds

732
P. Yogeeswari et al. / European Journal of Medicinal Chemistry 39 (2004) 729–734
Table 2
Table 4
Anticonvulsant activity and minimal motor impairment of aryl semicarba-
zones
Behavioral study on some selected compounds using actophotometer
Compounda Activity scoreb
Compound Intraperitoneal injection in micea
Control (24 h prior) Post-treatment
MES
screen
scPTZ
screen
scSTY
screenb
Neuro-
toxicity screen
0.5 h 4 h
0.5 h after
1 h after
4
5
6
8
10
16
21
24
320 27.73
519 13.38
180 30.22
154 10.90
408 32.96
303 22.66
373 32.75
247 15.66
531 17.22
421 26.78 *
61 9.69 *
343 21.11 NS
359 29.87 *
164 11.02 NS
0.5 h 4 h 0.5 h 4 h 0.5 h 4 h
1
2
3
4
100
100
–
–
–
300
300
–
–
–
–
–
x
x
x
x
x
x
100
–
c
300 100
113 10.30 ** 159 6.77 NS
300
–
–
48 9.66
41 2.21
20 6.12
11 7.25
44 4.56
33 2.11
27 1.02
12 2.35
12 7.35
46 2.44
–
300
–
100 300 300 f 300
c
d
d
d
5
6
8
–
–
–
–
–
–
–
–
–
100 300
–
–
Phenytoin c 267 31.12
300
–
100 100 300 300
100 100 100 300
300
a The compounds were tested at a dose of 30 mg/kg (i.p.).
b Each score represents the mean SEM of six mice, significantly diffe-
rent from the control score at P < 0.0001, * P < 0.008, ** P < 0.02 and NS at
P < 0.02 denotes not significant (Student’s t-test).
c
10
16
–
–
–
300
–
–
–
300 e
100 300
–
–
–
–
–
300
c
c Tested at 5 mg/kg p.o.
21
300 300 300
–
100 100 300 300
c
Table 5
24
25
27
28
31
32
–
–
–
–
–
–
300
300
300
300
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
300 e 300
–
–
–
–
–
–
–
CNS study on selected compounds in forced swim pool test
e
–
–
x
x
x
x
–
–
–
Compounda
Immobility timeb (s)
Control (24 h prior)
164.67 11.69
125.67 11.89
57 12.16
f
x
–
Post-treatment (60 min after)
168.53 12.32 NS
190.30 12.45
x
–
PEG
3
4
6
8
10
16
24
d
x
300
–
c
–
x
130.3 11.25
Phenytoing 30 30
–
100 100
134 12.70
205.00 11.63
Ethosuxi-
mide g
–
–
300
300
–
–
78.65 12.62
200 11.63
104.00 12.94 NS
137.30 12.49
a Doses of 30, 100 and 300 mg/kg were administered. The figures in the
table indicate the minimum dose whereby bioactivity was demonstrated in
half or more of the mice. The animals were examined 0.5 and 4 h after
injections were made. The dash (–) indicates an absence of activity at max
dose administered (300 mg/kg) and (x) indicates not tested.
b In the scSTY screen compounds 11 and 29 showed protection at
300 mg/kg for 0.5 h.
115.67 12.05
104.33 13.29
150.60 12.06 NS
187.3 13.09
Carbamazepinea 138.4 17.3
240.60 14.10
a The compounds were tested at a dose of 30 mg/kg (i.p.).
b Each value represents the mean SEM of six rats significantly different
from the control at P < 0.004 and NS denotes not significant at
P < 0.004 (Student’s t-test).
c In the MES screen, at 30 mg/kg compound 8 (1/4, 4 h) and at 100 mg/kg
compounds 2 (1/3, 4 h), 4 (1/3, 4 h), 16 (1/3, 4 h), 21 (2/3, 1 h) and 32 (1/7,
4 h).
significant CNS depression compared with the control at
P < 0.004. All other compounds tested were found to emerge
as CNS depressants as they increased the immobility time.
The conclusions drawn from the study are as follows.
Generally these aryl semicarbazones exhibited good protec-
tion against scSTY-induced seizures and hence could act
through inhibitory glycine receptors [25]. The present study
showed the increase in immobility time by the anticonvulsant
compounds and hence indicating facilitation of depression.
These compounds facilitated depression in the doses of
30 mg/kg i.p. These doses are lower than the anticonvulsant
dose, which suggest that the mechanism involved in the
anticonvulsant action and in the facilitation of depression
could be different. However, to confirm this fact, further
studies are required to be carried out.
d In the scPTZ screen, at 100 mg/kg, compounds 5 (1/5, 4 h), 6 (1/5, 4 h)
and 31 (1/5, 0.5 h), and at 300 mg/kg compound 5 (1/5, 0.5 and 4 h).
e In the scSTY screen, mild clonic jerks were observed with compounds
10 and 24 (300 mg/kg, 1/3). Compound 25 caused loss of righting reflex and
death (2/2, 300 mg/kg).
f In the neurotoxicity screen, at 100 mg/kg, compounds 4 (2/3, 2 h) and 27
(2/3, 2 h).
g Data from Refs. [7,17].
Table 3
Evaluation of some compounds in the MES test after oral administration
(30 mg/kg) to rats
Compound
Oral administration to ratsa
0.25 h
0.5 h
1 h
0
2 h
0
4 h
0
1
2
6
16
1
2
1
0
0
1
0
1
0
0
1
4
1
1
1
5. Experimental protocols
1
0
0
0
0
0
5.1. Chemistry
21
0
1
0
Phenytoin
3
3
3
Melting points were determined in one end open capillary
tubes on a Büchi 530 melting point apparatus and are uncor-
a The figures indicate the number of rats out of four which were protected.

P. Yogeeswari et al. / European Journal of Medicinal Chemistry 39 (2004) 729–734
733
rected. Infrared (IR) and proton nuclear magnetic resonance
(1H-NMR) spectra were recorded for the compounds on
Jasco IR Report 100 (KBr) and Brucker Avance (300 MHz)
instruments, respectively. Chemical shifts are reported in
parts per million (ppm) using tetramethyl silane (TMS) as an
internal standard. All exchangeable protons were confirmed
by addition of D2O. Elemental analyses (C, H, and N) were
undertaken with Perkin-Elmer model 240C analyzer. The
homogeneity of the compounds was monitored by ascending
thin layer chromatography (TLC) on silicagel-G (Merck)
coated aluminium plates, visualized by iodine vapor. Devel-
oping solvents were chloroform–methanol (9:1). The log P
values were determined using Alchemy-2000 and Scilog P
softwares (Tripos Co.).
5 (DMSO-d6): 2.28 (s, 3H, ArCH3), 6.81–7.8 (m, 7H,
ArH), 8.25 (s, 1H, imine H), 8.67 (s, 1H, ArNH, D2O ex-
changeable), 10.71 (s, 1H, CONH, D2O exchangeable),
10.06 (s, 1H,ArOH, D2O exchangeable); 8 (DMSO-d6): 2.35
(s, 3H, ArCH3), 7.20–8.31 (m, 7H, ArH), 8.10 (s, 1H, imine
H), 9.01 (s, 1H, ArNH, D2O exchangeable), 11.19 (s, 1H,
CONH, D2O exchangeable); 15 (DMSO-d6): 2.18 (s, 3H,
CH3), 2.30 (s, 3H, ArCH3), 6.74–7.78 (m, 7H, ArH), 8.62 (s,
1H, ArNH, D2O exchangeable), 10.01 (s, 1H, ArOH, D2O
exchangeable), 10.64 (s, 1H, CONH, D2O exchangeable); 19
(DMSO-d6): 2.24 (s, 3H, CH3), 2.37 (s, 3H, ArCH3), 7.24–
8.41 (m, 7H, ArH), 8.98 (s, 1H, ArNH, D2O exchangeable),
11.05 (s, 1H, CONH, D2O exchangeable); 21 (DMSO-d6):
2.21 (s, 6H, CH3), 2.34 (s, 3H, ArCH3), 7.12–7.30 (m, 3H,
ArH), 8.58 (s, 1H, ArNH, D2O exchangeable), 10.54 (s, 1H,
CONH, D2O exchangeable); 24 (DMSO-d6): 1.32–1.36 (t,
3H, CH3, J = 7.6 Hz), 1.82–1.88 (q, 2H, CH2, J = 7.6 Hz),
2.20 (s, 3H, CH3), 2.32 (s, 3H, ArCH3), 7.08–7.24 (m, 3H,
ArH), 8.62 (s, 1H, ArNH, D2O exchangeable), 10.61(s, 1H,
CONH, D2O exchangeable); 30 (DMSO-d6): 2.30 (s, 3H,
ArCH3), 6.94–8.28 (m, 6H, ArH), 9.32 (s, 1H, ArNH, D2O
exchangeable), 10.88 (s, 1H, NH isatinyl, D2O exchange-
able), 10.92 (s, 1H, CONH, D2O exchangeable); 31 (DMSO-
d6): 2.31 (s, 3H, ArCH3), 6.88–8.14 (m, 6H, ArH), 8.74 (s,
1H, ArNH, D2O exchangeable), 10.82 (s, 1H, NH isatinyl,
D2O exchangeable), 10.90 (s, 1H, CONH, D2O exchange-
able).
5.1.1. Synthesis of 3-chloro-2-methyl phenyl urea (1)
3-Chloro-2-methyl aniline (0.1 mol, 14.1 g, 11.8 ml) was
dissolved in 20 ml of glacial acetic acid and 10 ml of water.
To this, 0.1 mol of sodium cyanate (6.5 g) in 80 ml of warm
water was added with stirring. Allowed to stand for 30 min,
then cooled in ice and filtered with suction, and dried. Re-
crystallized from boiling water to yield 1 with m.p. 201 °C,
IR (KBr) mmax 3450, 1650, 840 cm–1, 1H-NMR (DMSO-d6) d
2.4 (s, 3H, CH3), 7.2–7.4 (m, 3H, ArH) 8.28 (s, 1H, ArNH,
D2O exchangeable), 9.33 (s, 2H, CONH2, D2O exchange-
able).
5.1.2. Synthesis of 3-chloro-2-methyl phenyl semicarbazide
(2) hydrochloride
5.2. Pharmacology
Equimolar quantities (0.05 mol) of 1 (9.2 g) and hydrazine
hydrate (2.5 ml) in ethanol were refluxed for 24 h with
stirring. The two-third volume of alcohol was distilled by
vacuum distillation unit and then poured into ice. The result-
ant precipitate was filtered, washed with water and dried. The
solid was recrystallized from 50 ml of 90% alcohol to which
25 ml of concentrated hydrochloric acid was added. The
precipitate of 2, hydrochloride, was filtered by vacuum and
dried. IR (KBr) mmax 3450, 3269, 1640, 840 cm–1; 1H-NMR
(CDCl3) d 2.33 (s, 3H, CH3), 5.56 (s, 2H, NH2, D2O ex-
changeable), 7.2–7.45 (m, 3H,ArH), 8.34 (s, 1H,ArNH, D2O
exchangeable), 9.6 (bs, 1H, NHNH2, D2O exchangeable).
The anticonvulsant evaluations were undertaken using
reported procedures [26–28]. Male albino mice (CF-1 strain
or Swiss, 18–25 g) and rats (Sprague–Dawley or Wistar,
100–150 g) were used as experimental animals. The tested
compounds were suspended in 0.5% methyl cellulose/water
mixture or in polyethylene glycol (PEG).
5.2.1. Anticonvulsant screening
Initially all the compounds were administered i.p. in a
volume of 0.01 ml/g body weight for mice and 0.004 ml/g
body weight for rats at doses of 30, 100 and 300 mg/kg to one
to four animals. Activity was established using the MES,
scPTZ and scSTY tests and these data are presented in
Table 2. Some selected derivatives described in this study
were examined for oral activity in the MES screen. The
results are presented in Table 3.
5.1.3. General method for the synthesis
of 3-chloro-2-methyl phenyl semicarbazones (3–33)
The title compounds were synthesized following proce-
dures reported earlier [7]. To a solution of 2 (0.005 mol,
1.175 g) in 25 ml of water was added sodium acetate
(0.005 mol, 0.41 g) in 2 ml water.About 25 ml of ethanol was
added to clear turbidity. This solution mixture was added to
an equimolar quantity of the appropriate aldehyde or ketone
in alcohol. Stirring was done if needed. Immediate precipita-
tion occurred and the solids were filtered, dried and recrys-
tallized from hot ethanol. The physical data of the semicar-
bazones are given in Table 1. The IR spectra of the
semicarbazone derivatives were identical in the following
aspects; 3450, 3300–3250, 1650, 1595, 840 cm–1. 1H-NMR
(300 MHz, d) spectra of some representative compounds are
as follows:
5.2.2. Neurotoxicity screening
Minimal motor impairment was measured in mice by the
rotorod test. The mice were trained to stay on an accelerating
rotorod that rotates at six revolutions per minute. The rod
diameter was 3.2 cm. Neurotoxicity was indicated by the
inability of the animal to maintain equilibrium on the rod for
at least 1 min in each of the three trials.
5.2.3. Behavioral testing
The titled compounds (30 mg/kg) were screened for their
behavioral effects using actophotometer [29] at 30 min and

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Acknowledgements
One of the authors Mr. R. Thirumurugan deeply acknowl-
edges the Council of Scientific and Industrial Research for
providing Senior Research Fellowship. The authors are
grateful to Mr. A.R. Subramanian, CDRI, Lucknow for the
generation of 1H-NMR and elemental analyses data.
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