Indium trichloride-catalyzed synthesis of some novel 2,2'-(N,N'- diarylamino)-4,4'-diaryl-5,5'-arylidenebisthiazoles and their insecticidal activity

Article abstract of DOI:10.1002/hc.20537

A series of novel 2,2'-(N,N'-diarylamino)-4,4'-diaryl-5,5'-arylidene- bisthiazoles 2 were rapidly and smoothly prepared in good yields by using non conventional techniques i.e. microwave or ultrasonic irradiation, through indium trichloride catalyzed elec

Full text of DOI:10.1002/hc.20537

Heteroatom Chemistry
Volume 20, Number 4, 2009
Indium Trichloride–Catalyzed Synthesis
ꢀ
ꢀ
of Some Novel 2,2 -(N,N -Diarylamino)-
ꢀ
ꢀ
4,4 -diaryl-5,5 -arylidenebisthiazoles and
Their Insecticidal Activity
Ragini Gupta,2 Deepti Sharma,1 and Prem Singh Verma1
1Centre of Advanced Studies, Department of Chemistry, University of Rajasthan,
Jaipur 302 004, India
2Department of Chemistry, Malaviya National Institute of Technology, Jaipur 302 017, India
Received 19 February 2009; revised 30 April 2009
of biological activities such as anti-inflammatory [1],
ABSTRACT:
A
series of novel 2,2ꢀ-(N,Nꢀ-
antiviral [2], antibacterial [3], antitumor [4], anal-
gesic [5], antioxidant [6], anticonvulsant [7], antihy-
pertensive [8], and hypoglycemic [9] activities. Thia-
zoles have also found application in other fields such
as polymers [10], liquid crystals [11], photonucle-
ases [12], fluorescent dyes [13], insectides [14], and
antioxidants [15]. Furthermore, the molecules that
incorporate a bithiazole moiety in which two thia-
zole rings are joined directly such as in bleomycin
[16] or a bisthiazole unit in which the two thiazole
rings are connected through a few intervening bonds
also exhibit antibacterial [17], anticancer [18], and
antiarthritic [19] activities.
Aminothiazole derivatives are highly electron
rich at position 5 of the ring and as a result are read-
ily substituted by electrophilic reactants. The entry
of the electrophilic reactants at position 5 or 5ꢀ of
the bisthiazole system depends on the nature of the
residue present at position 4 [20]. The acid-catalyzed
substitution reaction of electron-rich heterocyclic
compounds with p-dimethylaminobenzaldehyde is
known as Ehrlich test [21] for π-electron excessive
heterocycles. Protic acids and Lewis acids are both
known to promote this type of reaction.
diarylamino)-4,4ꢀ-diaryl-5,5ꢀ-arylidene-bisthiazoles 2
were rapidly and smoothly prepared in good yields by
using non conventional techniques i.e. microwave
or ultrasonic irradiation, through indium trichlo-
ride catalyzed electrophilic substitution reaction
of 2-(N-arylamino)-4-arylthiazoles 1 with various
arylaldehydes. All the synthesized compounds were
characterized on the basis of their elemental anal-
yses and spectral data (IR, PMR and Mass). The
synthesized compounds were also evaluated for their
insecticidal activity against Helicoverpa armigera
ꢁ
C
and gave promising results.
2009 Wiley Periodicals,
Inc. Heteroatom Chem 20:224–231, 2009; Published on-
line in Wiley InterScience (www.interscience.wiley.com).
DOI 10.1002/hc.20537
INTRODUCTION
Thiazoles and their derivatives are useful intermedi-
ates in organic synthesis and possess a broad range
Correspondence to: Ragini Gupta; e-mail: raginigupta@
mnit.ac.in.
Contract grant sponsor: Centre of Advanced Studies, Depart-
ment of Chemistry, University of Rajasthan, Jaipur, India.
Recently, indium trichloride has been found
to act as a mild and water-tolerant Lewis acid
catalyst in synthetic organic chemistry, for exam-
ple, Mukaiyama aldol reaction [22], Mannich-type
Contract grant number: JRF (to D.S.).
2009 Wiley Periodicals, Inc.
c
ꢀ
224

Novel 2,2ꢀ-(N,Nꢀ-Diarylamino)-4,4ꢀ-diaryl-5,5ꢀ-arylidenebisthiazoles and Their Insecticidal Activity 225
reaction [23], Diels-Alder reaction [24], aziridina-
and may bring out peculiar chemoselectivities, thus
opening up new synthetic methods [38]. Although
it has been widely presumed that ultrasound and
microwave provide differential assistance to com-
pletely different reaction pathways [39], there has
been a dearth of reports wherein the competitive ef-
ficacy of ultrasound and microwave toward selective
formation of competing procedures has been clearly
discerned.
A survey of literature revealed that no work
has been done on the synthesis of 2,2ꢀ-(N,Nꢀ-
diarylamino)-4,4ꢀ-diaryl-5,5ꢀ-arylidenebisthiazoles 2
using indium trichloride (20 mol%) via microwave
or ultrasound and any other method.
tion reaction [25], Friedal-Crafts reaction [26], Bar-
bier reaction [27], and Biginelli reaction [28]. It
can be conveniently used in both aqueous and non-
aqueous mediums. Moreover, indium(III) chloride
is stable under air and in water, and constitutes an
interesting catalyst for clean and green chemistry
due to possibility of recovery and recycling [29]. In
addition, it has a high coordination number and
possesses a fast coordination-dissociation equilib-
rium in aqueous solutions. This behavior of indium
trichloride prompted us to investigate its catalytic
activity for the electrophilic substitution reaction of
N-arylaminothiazoles.
Although the synthesis of 5,5ꢀ-bis-1,3-thiazoles
[30], 2,2ꢀ-bis-1,3-thiazoles [31], and 4,4ꢀ-(1,4-
RESULTS AND DISCUSSION
Synthesis
biphenylene)bis-1,3-thiazoles
[32]
has
been
reported, there is no report on the synthesis of 2,2ꢀ-
(N,Nꢀ-diarylamino)-4,4ꢀ-diaryl-5,5ꢀ-arylidenebisthia-
zoles 2 by the condensation of N-arylaminothiazoles
and aldehydes. Interest in their synthesis comes
from the fact that the cystothiazoles [33], having
a (2,4ꢀ)bisthiazole component, demonstrate potent
antifungal activity and function as novel inhibitors
of mitochondrial oxidation at a specific site on
cytochrome bc1 complex and bis(aminothiazolyl)-
methanes, which have been synthesized by react-
ing dichloropentadiones with thiourea and show
anticholinesterase activity [34].
A series of 2,2ꢀ-(N-Nꢀ-diarylamino)-4,4ꢀ-diaryl-5,5ꢀ-
arylidenebisthiazoles 2 has been synthesized and
identified. Electrophilic substitution reaction of 2-
(N-arylamino)-4-arylthiazoles 1 with various ary-
laldehydes in the molar ratio of 2:1 along with a
catalytic amount of anhydrous indium trichloride
under microwave or ultrasonic irradiation was per-
formed in good to excellent yields (Scheme 1). In
Y
Z
N
X
As environmental consciousness in chemical re-
search and industry increases, the challenge for
a sustainable environment calls for clean pro-
cedures. So, several procedures are now recom-
mended for green chemistry [35] involving new eco-
friendly reagents or catalysts, selective medium such
as water, ionic liquids, or solvent-free reactions,
or nonconventional energy sources such as ultra-
sound or microwaves. Encouraged by these obser-
vations and as a part of our ongoing research pro-
gram on arylaminothiazoles [36], we herein report
environmentally desirable synthesis of 2,2ꢀ-(N,Nꢀ-
diarylamino)-4,4ꢀ-diaryl-5,5ꢀ-arylidenebisthiazoles 2
using green chemistry techniques (microwave irra-
diation and ultrasonicaton) via indium trichloride–
catalyzed electrophilic substitution reaction. All the
synthesized compounds showed promising results
when screened for their insecticidal activity against
Helicoverpa armigera.
CHO
+
NH
S
(1)
InCl3
Y
Y
X
X
N
N
HN
NH
S
S
HC
Z
(a) Ultrasound method
(b) Microwave method
(c) Conventional method
(2)
2
X
Y
H
H
4-Cl
Z
H
4-Cl
H
a
b
c
d
e
f
g
h
i
H
H
H
H
H
H
H
H
H
4-Cl 4-Cl
4-F
Ultrasound and microwave have been widely
recognized as important enabling technologies in
organic synthesis due to a range of ensuing ben-
efits such as improved yields, shorter times, and
enhanced selectivity [37] in comparison with con-
ventional conditions. These techniques can induce
reactions that would otherwise be very laborious
H
4-Br 4-Cl
4-Br 4-F
4-Cl 4-F
4-Br 4-OCH3
4-Br 4-OCH3
j
3-Cl; 4-F
SCHEME 1
Heteroatom Chemistry DOI 10.1002/hc

226 Gupta, Sharma, and Verma
TABLE 1 Physical and Analytical Data of 2,2ꢀ-(N,Nꢀ-Diarylamino)-4,4ꢀ-diaryl-5,5ꢀ-arylidenebisthiazoles 2a–j
Analyses [Calculated (Found)] (%)
Compound
X
H
H
H
H
H
H
H
H
H
Y
Z
Molecular Formula
C37H28N4S2
Melting Point (◦C)
C
H
N
S
2a
2b
2c
2d
2e
2f
H
H
217
220
218
210
165
195
219
194
212
110
75.00
(74.83)
70.92
(70.79)
67.27
(67.18)
63.97
(63.91)
72.78
(72.72)
56.34
(56.26)
57.96
(57.87)
65.48
(65.44)
58.61
4.72
(4.59)
4.31
(4.34)
3.93
(3.89)
3.60
(3.53)
4.42
(4.45)
3.17
(3.11)
3.26
(3.21)
3.68
(3.57)
3.59
9.45
(9.41)
8.94
(8.89)
8.48
(8.42)
8.06
(8.09)
9.18
(9.14)
7.10
(7.05)
7.31
(7.26)
8.25
(8.21)
7.19
10.81
(10.77)
10.22
(10.15)
9.69
(8.54)
9.22
(9.13)
10.49
(10.51)
8.12
(8.05)
8.35
(8.30)
9.43
(9.36)
8.22
(8.14)
7.25
(7.29)
H
4-Cl
H
C37H27ClN4S2
C37H26Cl2N4S2
C37H25Cl3N4S2
C37H27FN4S2
4-Cl
4-Cl
H
4-Cl
4-F
4-Cl
4-F
4-F
4-Br
4-Br
4-Cl
C37H25Br2ClN4S2
C37H25Br2FN4S2
C37H25Cl2FN4S2
C38H28Br2N4OS2
2g
2h
2i
4-Br 4-OCH3
(58.65)
51.70
(51.66)
(3.53)
2.72
(2.65)
(7.12)
6.34
(6.38)
2j
3-Cl; 4-F 4-Br 4-OCH3 C38H24Br2Cl2F2N4OS2
the classical approach, the reaction proceeds with a
low yield of the products (15%–22%) by refluxing the
reactants for 16–22 h in dichloromethane. In an at-
tempt to improve the yields of reaction and acknowl-
edging the benefits of “green chemistry,” the same
reaction was performed under solvent-free condi-
tions (microwave and ultrasound irradiation).
ated for 10–20 min in a domestic microwave oven
to afford the title compounds in 80%–92% yield.
Under solvent-free conditions, the reaction is com-
pleted with higher yield because the eutectic mixture
having a uniform distribution of the reactants brings
the reacting species in close proximity to react than
in the solvent.
In the ultrasonic approach, sonication of 2-(N-
arylamino)-4-arylthiazoles 1 with various arylalde-
hydes using indium trichloride as a catalyst in an
ultrasonic cleaning bath gave 72%–84% yield of
the corresponding bisthiazole derivatives in 3–5 h.
The reaction rates and yields were dramatically en-
hanced by sonic waves because of cavitational col-
lapse under mild conditions. The same reactants
were thoroughly mixed without solvent and irradi-
The physical and analytical data of compounds 2
are given in Table 1. The synthetic step is illustrated
in Scheme 1. The comparative data of various pro-
cedures are tabulated in Table 2. All the synthesized
compounds were characterized by their IR, 1H NMR,
and fast atomic bombardment (FAB) mass spectral
data (Table 3).
In the IR spectra of 2-(N-arylamino)-4-
arylthiazoles 1, absorption bands at 3450–3100,
TABLE 2 Yield (%) and Time for the synthesis of 2,2ꢀ-(N,Nꢀ-Diarylamino)-4,4ꢀ-diaryl-5,5ꢀ-arylidenebisthiazoles 2a–j
Yield (%)
Time (min)
Microwave
Compound
Ultrasound
Microwave
Conventional
Ultrasound
Conventional
2a
2b
2c
2d
2e
2f
2g
2h
2i
73.0
73.8
74.6
76.0
72.0
80.0
81.5
80.4
82.2
84.7
80.0
84.0
85.0
87.5
81.7
91.0
88.5
87.0
91.5
92.0
15.0
18.0
18.0
20.0
15.0
21.0
20.0
20.0
21.0
22.0
[5]
[4.5]
[4]
[4]
[5]
[3.5]
[3]
[4]
[4]
20
15
12
15
20
10
12
15
20
10
[20]
[18]
[18]
[21]
[22]
[20]
[16]
[22]
[20]
[16]
2j
[3]
Values given in square brackets are in hours.
Heteroatom Chemistry DOI 10.1002/hc

Novel 2,2ꢀ-(N,Nꢀ-Diarylamino)-4,4ꢀ-diaryl-5,5ꢀ-arylidenebisthiazoles and Their Insecticidal Activity 227
TABLE 3 Spectral Data of 2,2ꢀ-(N,Nꢀ-Diarylamino)-4,4ꢀ-diaryl-5,5ꢀ-arylidenebisthiazoles 2a–j
Compound
IR (KBr) (vmax) (cm−1
)
1H NMR (in CDCl3) (δ ppm)
FAB Mass (m/z) (M+)
2a
3120 (N H str.), 3045 (aromatic C H str.), 2840
(aliphatic C H str.), 1570 (aromatic C C str.), 1500
(C N str.), 1310 (C S str.)
7.01–7.34 (m, ArH, 25H) 7.38
(s, NH, 2H), 6.02 (s, CH, 1H)
592
2b
2c
2d
2e
2f
3150 (N H str.), 3050 (aromatic C H str.), 2850
(aliphatic C H str.), 1580 (aromatic C C str.), 1510
(C N str.), 1350 (C S str.), 670 (C Cl str.)
3155 (N H str.), 3059 (aromatic C H str.), 2853
(aliphatic C H str.), 1588 (aromatic C C str.), 1516
(C N str.), 1352 (C S str.), 675 (C Cl str.)
3160 (N H str.), 3055 (aromatic C H str.), 2900
(aliphatic C H str.), 1593 (aromatic C C str.), 1510
(C N str.), 1349 (C S str.), 688 (C Cl str.)
3220 (N H str.), 3055 (aromatic C H str.), 2995
(aliphatic C H str.), 1615 (aromatic C C str.), 1518
(C N str.), 1356 (C S str.), 1114 (C Cl str.)
3217 (N H str.), 3065 (aromatic C H str.), 2993
(aliphatic C H str.), 1620 (aromatic C C str.), 1519
(C N str.), 1358 (C S str.), 692 (C Cl str.), 561
(C-Br str.)
6.89–7.35 (m, ArH, 25H) 7.37
(s, NH, 2H), 6.53 (s, CH, 1H)
626/628
660/662
694/696
610
7.01–7.46 (m, ArH, 23H) 7.59
(s, NH, 2H), 6.64 (s, CH, 1H)
7.01–7.47 (m, ArH, 22H) 7.62
(s, NH, 2H), 6.64 (s, CH, 1H)
6.90–7.45 (m, ArH, 24H) 7.62
(s, NH, 2H), 6.50 (s, CH, 1H)
6.83–7.49 (m, ArH, 22H) 7.72
(s, NH, 2H), 6.49 (s, CH, 1H)
788/790
2g
2h
3157 (N H str.), 3062 (aromatic C H str.), 2900
(aliphatic C H str.), 1620 (aromatic C C str.), 1512
(C N str.), 1356 (C S str.), 1100 (C F str.), 575
(C-Br str.)
3158 (N H str.), 3050 (aromatic C H str.), 2960
(aliphatic C H str.), 1610 (aromatic C C str.), 1515
(C N str.), 1355 (C S str.), 1110 (C F str.), 690
(C Cl str.)
6.91–7.36 (m, ArH, 22H) 7.49
(s, NH, 2H), 6.60 (s, CH, 1H)
766/768
678/680
6.87–7.36 (m, ArH, 22H) 7.42
(s, NH, 2H), 6.48 (s, CH, 1H)
2i
2j
3158 (N H str.), 3060 (aromatic C H str.), 2950
(aliphatic C H str.), 1600 (aromatic C C str.), 1520
(C N str.), 1355 (C S str.), 560 (C-Br str.)
3255 (N H str.), 3070 (aromatic C H str.), 2995
(aliphatic C H str.), 1625 (aromatic C C str.), 1526
(C N str.), 1360 (C S str.), 1120 (C F str.), 680
(C Cl str.), 570 (C-Br str.)
6.91–7.48 (m, ArH, 22H) 7.86
(s, NH, 2H), 6.59 (s, CH, 1H),
3.82 (s, OCH3, 3H)
7.02–7.86 (m, ArH, 18H) 8.10
(s, NH, 2H), 6.81 (s, CH, 1H)
778/780
882/884/886
1560–1530, and 1352–1330 cm−1 are attributed
to >NH, >C N, and >C S stretching vibra-
tions, respectively. The aromatic double bond
(>C C<) appears between 1600–1594 cm−1. The IR
spectra of 2,2ꢀ-(N,Nꢀ-diarylamino)-4,4ꢀ-diaryl-5,5ꢀ-
arylidenebisthiazoles 2 exhibits the >NH stretching
vibration at 3255–3120 cm−1 and phenyl ring skeletal
>C C< vibrations at 1625–1570 cm−1. The promi-
nent peak between (1526–1500) cm−1 has been at-
tributed to >C N stretching vibrations and (1360–
1310) cm−1 have been assigned to >C S stretching
frequencies. The strong absorption bands at 575–
560, 690–670, and 1114–1100 cm−1 have been at-
tributed to Ar-Br, Ar-Cl, and Ar-F stretching modes.
An additional peak between 2995 and 2840 cm−1 at-
tributed to aliphatic C H stretching vibration that
was not present earlier in compounds 1 is also ob-
served.
onance signal of N H is observed in the region
from δ 7.3 to 7.8 ppm as a singlet, which is D2O
exchangeable. Aromatic protons are observed as
a multiplet from δ 6.9 to 7.8 ppm. In the 1H
NMR spectra of 2,2ꢀ-(N,N-diarylamino)-4,4ꢀ-diaryl-
5,5ꢀ-arylidenebisthiazoles 2, the disappearance of
resonance signal due to methine C H proton at
C-5 position of thiazole moiety and the appearance
of a sharp singlet at δ 6.25–6.64 ppm support the for-
mation of bisthiazoles. The position of aromatic and
N H resonance signals remains unaltered. Aromatic
protons appear as a complex multiplet in the region
from δ 6.83 to 7.86 ppm and the resonance signal of
N H appears as a singlet from δ 7.36 to 8.10 ppm,
which is D2O exchangeable.
Final confirmation is achieved from FAB mass
spectra, which exhibit molecular ion peak (M+)
of compounds 2 corresponding to their molecular
masses. Mass spectrum of compound 2i shows char-
acteristic molecular ion cluster m/z at 778/780(base
peak)/782 due to the presence of two bromine atoms
In the PMR spectra of compounds 1, methine
proton at C-5 position of thiazole moiety shows
a resonance signal at δ 5.9–6.2 ppm and the res-
Heteroatom Chemistry DOI 10.1002/hc

228 Gupta, Sharma, and Verma
TABLE 4 Percentage Mortality of Helicoverpa armigera on 1, 3, 5, and 7 Days After the Treatment by Food Dipping Method
for Compounds 2a–j
1 Day
3 Days
0.025
5 Days
0.025
7 Days
0.025
Compound
0.05
0.025
0.05
0.05
0.05
2a
35
(36.17)
35
25
(29.94)
30
50
(45.00)
50
40
(39.15)
40
65
(53.72)
75
50
(45.00)
50
85
(67.79)
90
60
(50.78)
65
2b
(36.25)
50
(33.17)
30
(44.99)
60
(39.19)
50
(60.06)
75
(45.00)
60
(71.86)
95
(53.82)
65
2c
(45.01)
55
(33.11)
35
(50.78)
65
(45.00)
50
(60.06)
85
(50.78)
65
(77.92)
100
(53.72)
70
2d
(47.91)
40
(36.21)
30
(53.75)
55
(45.00)
40
(67.79)
70
(53.75)
55
(85.94)
90
(56.79)
65
2e
(39.17)
55
(33.17)
40
(47.87)
70
(39.22)
50
(56.83)
90
(47.90)
65
(71.86)
100
(53.75)
70
2f
(47.88)
60
(39.16)
35
(56.94)
70
(45.00)
50
(71.86)
100
(53.83)
60
(85.94)
100
(56.98)
75
2g
(50.80)
55
(36.21)
40
(56.83)
85
(45.00)
60
(85.94)
100
(50.78)
70
(85.94)
100
(60.20)
75
2h
(47.90)
50
(39.23)
35
(67.79)
65
(50.80)
55
(85.94)
80
(56.83)
60
(85.94)
100
(60.20)
65
2i
(45.00)
60
(50.77)
25
(29.94)
0
(36.25)
40
(39.20)
(53.82)
85
(67.79)
40
(39.22)
0
(47.88)
55
(47.90)
(63.52)
100
(85.94)
60
(50.80)
0
(50.80)
70
(56.83)
(85.94)
100
(85.94)
75
(60.20)
0
(53.82)
80
(63.52)
2j
Endosulfan
Control
(4.05)
1.79
5.06
9.43
(4.05)
1.97
5.58
8.41
(4.05)
1.48
4.19
(4.05)
1.76
4.98
Standard Error of Mean SEm
Critical difference 5%
CoefÞcient of variance %
5.19
5.42
Figures in parenthesis are angular transformation values.
in the peak ratio of 1.2:2.3:1. When two bromine
atoms are present in the compound, the ideal con-
dition for the peak ratio is 1:2:1 due to M+, M +
2, and M + 4 ions [40]. Slight variation that is ob-
served from the ideal values can be attributed to the
contribution by isotopic sulfur, carbon, and hydro-
gen. Other peaks at 705 (22.85%), 602 (14.28%), 571
(20.0%), 525 (65.71%), 449 (34.28%), 422 (34.28%),
407 (17.14%), 390 (2.85%), 328 (8.57%), 299
(8.57%), 258 (77.14%), and 195 (14.28%) were also
observed.
In the present study, all the synthesized com-
pounds 2a–j were screened for their insecticidal ac-
tivity, which was measured on third instar larvae
of H armigera at the Department of Entomology,
Agricultural Research Station, Durgapura, Jaipur,
by food dipping method [41]. Different instar larvae
were collected from the local chickpea (Cicer ariet-
inum L.) fields in January and a larva along with
chickpea leaves was placed in a plastic container
with a perforated lid (10-g capacity) to avoid can-
nibalism. The stock culture was maintained.
A test solution was prepared by dissolving the
compound in 1–2 mL of acetone, then adding wa-
ter to make up the volume up to 1 L. Two doses of
0.05% and 0.025% were selected for inoculation. For
control, only acetone and water mixture was used.
For comparison, a standard 0.05% solution of endo-
sulfan was also prepared in a similar way. The third
instar larvae were used from the stock culture. Five
insects were kept together in a container and four
such replicates were prepared for both the concen-
trations of each compound. Chickpea shoots (2–3 g)
were soaked in solutions for 10 s and dried for 3–4
Insecticidal Activity
Helicoverpa armigera (Lepidoptera; Noctuidae), the
old-world worm, is a highly polyphagous insect. This
moth is a major pest threat because its larva can feed
on a wide range of economically important crops in-
cluding cotton, corn, tomato, legumes, and tobacco.
Polyphagy, high mobility, high fecundity, and facul-
tative diapauses are its key physiological, behavioral,
and ecological characteristics that facilitate its sur-
vival even under unstable habitats.
Heteroatom Chemistry DOI 10.1002/hc

Novel 2,2ꢀ-(N,Nꢀ-Diarylamino)-4,4ꢀ-diaryl-5,5ꢀ-arylidenebisthiazoles and Their Insecticidal Activity 229
120
100
80
60
40
20
0
0
0
0
0
0.05
0.025
0.05
0.025
0.05
0.025
0.05
0.025
1 Day
3 Days
5 Days
7 Days
Treatment
2a 2b 2c 2d 2e 2f 2g 2h 2i 2j Endosulfan Control
FIGURE 1 Percentage mortality of Helicoverpa armigera on 1, 3, 5, and 7 days after the treatment.
min at room temperature. These shoots were then in-
troduced in the plastic container containing larvae.
The percentage mortality of the larvae was recorded
after 1, 3, 5, and 7 days. The moribund insects were
also considered dead.
The percentage figures were then converted to
the angular transformation values, which were then
subjected to statistical analysis of completely ran-
domized design technique [42]. The results obtained
are presented in Table 4 (Fig. 1).
Initially after 24 h of the treatment, compound
2j showed higher activity (60% mortality at 0.05 ppm
and 40% mortality at 0.025 ppm), but after 3 days,
both compounds 2j and 2h showed higher bioactiv-
ity than the others. At this time, compound 2j (X =
3-Cl, 4-F, Y = 4-Br, Z = 4-OCH3) was found to be
the most potent at both the concentrations. Com-
pound 2h (X = H, Y = 4-Cl, Z = 4-F) was at par with
compound 2j and was also found to be a better insec-
ticide. After 5–7 days, all the synthesized compounds
showed significantly higher bioactivity, even better
than endosulfan at same dosage level. No mortal-
ity was found in the untreated control. Final obser-
vation regarding the mortality was performed after
7 days of the treatment. The results are discussed
with respect to the variation associated with the aryl
moiety.
activity of 2,2ꢀ-(N,Nꢀ-diarylamino)-4,4ꢀ-diaryl-5,5ꢀ-
arylidenebisthiazoles against the old-world worm
increases.
CONCLUSION
In summary, we have developed
a
simple,
novel, and efficient synthetic protocol for the
synthesis of 2,2ꢀ-(N,Nꢀ-diarylamino)-4,4ꢀ-diaryl-5,5ꢀ-
arylidenebisthiazoles using a catalytic amount of
anhydrous indium trichloride under microwave or
ultrasonic irradiation by electrophilic substitution
reaction of 2-(N-arylamino)-4-arylthiazoles 1 with
various arylaldehydes. The short reaction time cou-
pled with the simplicity of the reaction procedure
makes this method one of the most efficient methods
for the synthesis of this class of compounds. On the
basis of insecticidal evaluation, compounds 2h and
2j seem to be very attractive as insecticidal agents
against H. armigera.
EXPERIMENTAL
All melting points were determined in open glass
capillary tubes and are uncorrected. IR spectra
(vmax in cm−1) were recorded on an FT-IR model
Shimadzu-8400S grating infrared spectrophotome-
ter using KBr pellets. PMR spectra were recorded
on a JEOL-AL 300 spectrophotometer at 300 MHz
using TMS as an internal standard (chemical shift
in δ ppm) and CDCl3 as a solvent. IR and PMR
spectra were recorded at the Department of Chem-
istry, University of Rajasthan, Jaipur. FAB mass
By comparing the insecticidal activities of com-
pounds 2a–j, it was found that their activities against
H. armigera increased in the following order: 2j
> 2h > 2g > 2f > 2d > 2i > 2c > 2e > 2b
> 2a. So, it can be concluded that with the in-
crease of electron-withdrawing power, insecticidal
Heteroatom Chemistry DOI 10.1002/hc

230 Gupta, Sharma, and Verma
spectra were recorded on a JEOL SX 102/DA-6000
mass spectrometer/data system using argon/xenon
(6 kV, 10 mA) as the FAB gas. An Elentar Vario
EL III automatic CHNS analyzer was used for ele-
mental analyses. FAB mass spectra and CHNS anal-
yses were recorded at the Central Drug Research In-
stitute, Lucknow, India. Microwave irradiation was
carried out in an LG MS-194A household microwave
oven with a maximum 800 W power and 2450 MHz
frequency. Sonication was performed in a Toshcon
model SW 4 cleaner (with a frequency of 37 kHz and
operating at a maximum power of 150 W). The purity
of the compounds was checked by TLC using silica
gel (60–120 mesh) as the adsorbent, under UV light
or iodine-accomplished visualization. All common
reagents and solvents were used as obtained from
commercial suppliers without further purification.
2-(N-Arylamino)-4-arylthiozoles 1 were prepared by
the following literature method [43].
(20 mol%, 0.44 g) as a catalyst were mixed into a
conical flask (100 mL) and exposed to microwave ir-
radiation for 10–20 min (intermittently with 1-min
cooling interval) at maximum power (800 W). The
progress of the reaction was monitored by TLC us-
ing C6H6:EtOAC (95:5) as the eluant and the reac-
tion was run to completion. When irradiation was
stopped, the final temperature was measured by
introducing a glass thermometer into the reaction
mixture (65◦C–70◦C). After cooling it to room tem-
perature, the reaction mixture was quenched with
water and extracted with CH2Cl2 (3 × 10 mL). The
combined organic layers were dried over anhydrous
Na2SO4, filtered, and evaporated to dryness under
reduced pressure. Further purification was accom-
plished by column chromatography using silica gel
(60–120 mesh) as the stationary phase and solvent of
increasing polarity as the mobile phase. Pure bisthi-
azole was obtained in pet ether:benzene (20:80) as
yellow crystalline needles.
Method a
Method c
A
mixture of 2-(N-Arylamino)-4-arylthiazole
(1 mmol), arylaldehyde (0.5 mmol), and anhydrous
indium trichloride (20 mol%, 0.44 g) in CH2Cl2
(20 mL) was taken in a Pyrex conical flask (250
mL). The reaction flask was then placed in the
maximum energy area in an ultrasonic cleaning
bath (observation of the surface of the reaction
solution during vertical adjustment of flask depth
shows the optimum position by the point at which
maximum surface disturbance occurs) and then
it was sonicated for the time period as indicated
in Table 2. The bath temperature (30◦C–35◦C) was
controlled by the addition or removal of water. The
progress of the reaction was monitored by TLC
using C6H6:EtOAC (95:5) as the solvent system.
Sonication was continued until reactants disap-
peared as indicated by TLC. After the completion
of the reaction, the mixture was cooled to room
temperature, diluted with water, and extracted
with CH2Cl2 (3 × 10 mL). The combined organic
layers were dried over anhydrous Na2SO4, filtered,
and evaporated to dryness under reduced pressure.
Further purification was accomplished by column
chromatography using silica gel (60–120 mesh)
as the stationary phase and solvent of increasing
polarity as the mobile phase. Pure bisthiazole was
obtained in pet ether:benzene (20:80) as yellow
crystalline needles.
2-(N-Arylamino)-4-arylthiazole (1 mmol) and ary-
laldehyde (0.5 mmol) in dichloromethane were re-
fluxed in the presence of anhydrous indium trichlo-
ride (20 mol%, 0.44 g) as a catalyst for 16–22 h.
After the reaction was complete (checked by TLC),
the resulting mixture was poured into ice-cold wa-
ter and extracted with CH2Cl2 (3 × 10 mL). The or-
ganic layers were combined, dried over anhydrous
Na2SO4, filtered, and evaporated to dryness under
reduced pressure. Further purification was accom-
plished by column chromatography using silica gel
(60–120 mesh) as the stationary phase and solvent of
increasing polarity as the mobile phase. Pure bisthi-
azole was obtained in pet ether:benzene (20:80) as
yellow crystalline needles.
ACKNOWLEDGMENTS
The authors thank Dr. K. P. Madhusudanan, Deputy
Director and Head, Sophisticated Analytical In-
strument Facility, Central Drug Research Institute,
Lucknow, India, for elemental analyses and spectral
data. The authors also thank Dr. Swaroop Singh,
Durgapura Agricultural Research Station, Jaipur,
India, for providing necessary facilities during in-
secticidal evaluation.
Method b
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