Insecticidal Evaluation and [4+2] Aza-Diels-Alder Synthesis of 3,7-Diaryl-6,7-dihydro-5H-6-substituted Thiazolo[3,2-a]pyrimidin-5-ones Under Coupled Ultrasonic Irradiation and PTC

Article abstract of DOI:10.1002/jhet.776

(Chemical Equation Presented) A series of 3,7-diaryl-6,7-dihydro-5H-6-substituted-thiazolo[3,2-a]pyrimidin-5-ones (3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j) were synthesized by the [4+2] cycloaddition reaction of 2-arylideneamino-4-arylthiazoles (2a-j) with

Full text of DOI:10.1002/jhet.776

Month 2014
Insecticidal Evaluation and [4+2] Aza‐Diels‐Alder Synthesis of
3,7‐Diaryl‐6,7‐dihydro‐5H‐6‐substituted
Thiazolo[3,2‐a]pyrimidin‐5‐ones Under Coupled Ultrasonic
Irradiation and PTC
a
b
b
a
*
Ragini Gupta, Deepti Sharma, P. S. Verma, and Anshu Jain
aDepartment of Chemistry, Malaviya National Institute of Technology, Jaipur 302017, India
bDepartment of Chemistry, Centre of Advanced Studies, University of Rajasthan,
Jaipur 302004, India
*
E-mail: raginigupta@mnit.ac.in
Received June 27, 2010
DOI 10.1002/jhet.776
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
A series of 3,7‐diaryl‐6,7‐dihydro‐5H‐6‐substituted‐thiazolo[3,2‐a]pyrimidin‐5‐ones (3a–j) were synthe-
sized by the [4+2] cycloaddition reaction of 2‐arylideneamino‐4‐arylthiazoles (2a–j) with in situ generated
monosubstituted ketenes under PTC conditions coupled with ultrasonication in good to excellent yields.
All the synthesized compounds were characterized on the basis of their spectral (IR, PMR, and Mass) and
analytical data. The synthesized compounds were also screened for their insecticidal activity against
Helicoverpa armigera and some of them showed promising activity.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
cycloaddition process, and the rapid and rigorous develop-
ment in this area has led to several reviews highlighting the
utility of azadienes as readily available templates in the
synthesis of novel heterocycles and complex natural prod-
ucts [15]. Dienes containing two nitrogen atoms have
attracted attention of chemists in recent years because of
their importance in natural product synthesis [16]. There
have been numerous reports concerning the participation
of 1,3‐diazabuta‐1,3‐dienes as 4π component in cycloaddi-
tion reactions with isocyanides [17], oxazolines [18], en-
amines [19], alkynes [20], etc. On the other hand, the
reaction of ketenes with 1,3‐aza‐1,3‐butadienes is reported
to undergo [4+2] and [2+2] cycloadditions [21]. A vast
prevalence of such reported cycloadditions correspond to
[4+2] cycloadditions in which 1,3‐aza‐1,3‐dienes adds as
the 4π component across the C C bond of the ketenes [22].
Ketenes exhibit very rich cycloaddition chemistry be-
cause of their structural and electronic peculiarities [23].
Despite the formal similarity existing in the cycloaddition
reaction between ketenes and double bonds, the actual
mechanisms varies significantly from one system to an-
other. Thus, [4+2] cycloaddtion between ketenes and 1,3‐
diaza‐1,3‐butadienes is believed to take place via a two‐
step process [24], in which the first step is a nucleophilic
attack of diazabutadiene over the sp‐hydridized carbon
atom of the ketene to form a zwitterionic intermediate,
whose disrotatory thermal electrocylization leads to the
formation of corresponding thiazolo[3,2‐a]pyrimidinones.
A survey of literature revealed that although there are
Thiazole and pyrimidine nuclei are the active core moi-
eties of various bioactive molecules. In general, heterocy-
cles encompassing a pyrimidine unit have found wide
applications in a spectrum of biological and therapeutic
areas [1]. Thus, the heterocyclic system resulting from
the annulation of a pyrimidine ring on the biologically ver-
satile thiazole nucleus is an attractive scaffold to be utilized
for exploiting chemical diversity. The bicyclic thiazolo
[3,2‐a]pyrimidine ring system has received a lot of atten-
tion in the literature because it exhibits significant biologi-
cal activities such as antibacterial [2], antifungal [3],
anticancer [4], anti‐inflammatory [5], immunomodulatory
[6], antagonistic [7], and insecticidal [8] activities. These
compounds have been reported to be synthesized by the re-
action of 2‐aminothiazole with β‐ketoester [9],
diethylethoxymethylmalanoate [10], 2‐acetylbutyrolactone
and POCl3 [11], 2‐chloronicotinic acid [12], and methyl
acrylate in presence of hydroquinone [13]. However, most
of the reported methods invariably suffer from cumber-
some experimental procedures and low isolated yields.
The hetero‐Diels‐Alder methodology, using azadienes,
represents the most attractive and important approach for
the synthesis of nitrogen‐containing six‐membered hetero-
cyclic compounds including pyrimidines because of their
potentially powerful and straightforward construction of
heterocycles with high control of stererochemistry [14].
Extensive studies have been carried out on this [4+2]
Copyright © 2014 HeteroCorporation

R. Gupta, D. Sharma, P. S. Verma, and A. Jain
Vol 000
many procedures for the synthesis of ketenes, e.g. genera-
tion by the cracking of acetone or by the treatment of
alkanoyl/aroylhalide with triethylamine are common
methods for the preparation of ketene [25] but to the best
of our knowledge, no work has been done to synthesize ke-
tene in situ via phase transfer catalysis (PTC). So, now we
wish to report a novel strategy for synthesizing 3,7‐diaryl‐
6,7‐dihydro‐5H‐6‐substituted‐thiazolo[3,2‐a]pyrimidin‐5‐
ones (3a–j) via solid liquid PTC coupled with ultrasound
irradiation.
thiazolo[3,2‐a]pyrimidin‐5‐ones (3) via PTC coupled with
ultrasonic irradiation, wherein not only the reaction time
has been brought down in comparison to conventional
method but also results in improved yields. All the syn-
thesized compounds have been screened for their insecti-
cidal activity against Helicoverpa armigera showing
promising results.
RESULTS AND DISCUSSION
PTC is a versatile, well‐established Green chemistry
technique, applied with several advantages to a number
of organic reactions wherein the reacting species located
in mutually immiscible phases are brought about or accel-
erated [26]. The reaction is carried out in the presence of
concentrated aqueous solution of sodium or potassium hy-
droxide or solid powdered KOH/NaOH and a phase trans-
fer catalyst [27], such as quaternary ammonium salt, crown
ether, polyethylene glycol and cryptand which allow the
transfer of the hydroxide in the organic phase. These
methods are now recognized as viable environmentally be-
nign alternatives. Searching for a more effective condition
to enhance the reaction or to elevate the conversions is the
primary purpose in PTC in combination with ultrasonic
waves [28]. In this regard, several nonconventional
methods are emerging that involve reactions in aqueous
media or those that are accelerated by exposure to micro-
wave or ultrasound irradiation.
Ultrasound has been used in heterogeneous chemistry for
several years and has been shown to increase the efficacy
of processes by emulsifying liquid–liquid system or by pro-
ducing erosion, disruption and dispersion of solid particles
[29]. The driving force for sonochemistry is cavitation, and
so general requirement is that at least one of the phases of
the reaction mixture should be a liquid. Furthermore,
micromixing effects produced by cavitation phenomena
increase the mass transfer around the solid particles and the
phase boundary. As PTC strongly depends on mass transfer,
the great interest of ultrasound for both liquid–liquid and
solid–liquid PTC can easily be understood.
Sonochemical cycloadditions, sensitive to both thermal
and pressure effects, would be affected by cavitational ef-
fects provided that enough volatile substance may enter
into the microbubbles, thereby undergoing bond cleavage
or transformation into excited species [30]. Thus,
cylcoadditions can be accelerated in terms of higher yield
or shorter reaction time when sonication is applied.
In light of above observations and in continuation to
our previous work on cycloaddition reactions [31] and
PTC [32], we thought it worthwhile to synthesize deriva-
tives of these biologically useful heterocycles by using
simple, convenient and mild phase transfer catalyzed [4
+2] azadiene‐ketene cycloaddition approach leading to
the synthesis of 3,7‐diaryl‐6,7‐dihydro‐5H‐6‐substitued‐
Synthesis. 2‐Amino‐4‐arylthiazoles (1) were prepared
by reacting α‐bromoacetophenones (phenacyl bromides)
and thiourea by following the classical Hantzsch
synthesis. These 2‐amino‐4‐arylthiazoles (1) were
condensed with arylaldehydes, in refluxing alcohol, to
give 2‐arylideneamino‐4‐arylthiazoles (Schiff’s base) (2).
PTC of 2‐arylideneamino‐4‐arylthiazoles (2) with in situ
generated monosubstituted ketenes such as chloro,
bromo, phenylketenes in the presence of ultrasonic waves
gave the desired titled 3,7‐diaryl‐6,7‐dihydro‐5H‐6‐
substitued‐thiazolo[3,2‐a]pyrimidin‐5‐ones (3) in good to
excellent yields compared with conventional procedure.
The synthetic steps are illustrated in Scheme 1, and a
possible mechanism has been proposed in Scheme 2. In
this mechanism, 2‐arylideneamino‐4‐arylthiazole (2)
(Schiff’s base) comprises a diazadiene system, acts as the
4π component and the ketene acts as the 2π component
in the [4+2] cycloaddition.
In solid–liquid PTC, a mixture of 2‐arylideneamino‐4‐
arylthiazole (2), n‐TBAHSO4, and solid powdered KOH
was dissolved in dry THF and well stirred at room temper-
ature. To this, alkanoyl/aroylhalide in tetrahydrofuran was
added dropwise with constant stirring. The solid KOH con-
tains the nucleophilic anion and the organic phase contains
the organic electrophile. The phase transfer catalyst n‐
TBAHSO4 transfers the anion from the surface of solid
KOH to the substituted alkanoyl/aroylhalide and ketene is
formed in the process of anion exchange. The six‐mem-
bered ring formation takes place by [4+2] cycloaddition
to yield the desired products (3).
In the traditional approach 3,7‐diaryl‐6,7‐dihydro‐5H‐6‐
substituted thiazolo[3,2‐a]pyrimidin‐5‐ones (3) were syn-
thesized by the dropwise addition of bromoacetyl
chloride/chloroacetyl chloride/phenylacetyl chloride in
THF to a solution of 2‐arylideneamino‐4‐arylthiazoles
(2), n‐TBAHSO4 and solid powdered KOH in THF with
continuous stirring. The reaction proceeds with low yield
(53–65%) after stirring for 7–9 h at room temperature. In
an attempt to improve the yields of reaction and acknowl-
edging the benefits of “green chemistry,” the same reaction
was performed under ultrasounic irradiation. In ultrasonic
approach, a solution of thiazolic‐1,3‐diazadienes (2), n‐
TBAHSO and powdered KOH in THF on sonication with
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014 Insecticidal Evaluation and [4+2] Aza-Diels-Alder Synthesis of 3,7-Diaryl-6,7-dihydro- 5H-
6-substituted thiazolo[3,2-a]pyrimidin-5-ones Under Coupled Ultrasonic Irradiation and PTC
Scheme 1
bromoacetyl chloride/chloroacetyl chloride/phenylacetyl
chloride in an ultrasonic bath gave 69–82% yield of the
corresponding thiazole pyrimidinones (3) in 2–3 h. The re-
action rates and yields were dramatically enhanced by
sonic waves due to cavitational collapse than the classical
method. The comparative data of both the procedures is
tabulated in Table 1.
In the IR spectra of 2‐amino‐4‐arylthiazoles (1), a broad
absorption band from 3450 to 3400 cm−1 due to NH2
stretching vibration was observed. Aromatic C H
stretching absorption peak appeared in the region of
3285–3110 cm−1. The strong absorption band from 1600
to 1580 cm−1, 1550 to 1540 cm−1, and 1340 to 1325 cm−1
was assigned to aromatic >C C, >C N, and >C S stretching
modes, respectively.
In the IR spectra of 2‐arylideneamino‐4‐arylthiozoles
(2), disappearance of NH2 stretching vibration and a new
absorption peak due to >C N group from 1668 to 1635 cm−1
was observed. Aromatic C H and aliphatic C H stretching
vibrations were observed from 3080 to 3025 cm−1 and
2940 to 2850 cm−1, respectively. Aromatic >C C< absorp-
tion band appeared in the region of 1640–1625 cm−1. The
strong absorption bands from 1250 to 1240 cm−1, 650
cm−1, and 290 to 570 cm−1 have been attributed to Ar‐F,
Ar‐Cl, and Ar‐Br stretching modes, respectively.
The IR spectra of 3,7‐diaryl‐6,7‐dihydro‐5H‐6‐
substituted thiazolo[3,2‐a]pyrimidin‐5‐ones (3a–j) exhib-
ited a characteristic absorption band in the region of
1725–1705 cm−1 due to >C O group which was at much
lower wave numbers than that reported for azetidinone car-
bonyl group [33]. The azetidinone molecule which is a
strained four‐membered ring shows >C O absorption at
high wave numbers (1780–1775 cm−1). This observation
rules out the possible [2+2] cycloaddition between
thiazolic diazadiene (2) and substituted ketene (Scheme 3).
Mazumdar et al. [22c] have also observed that in case of
reactions of 1,3‐diaza‐1,3‐butadienes with diphenylketene,
the [2+2] cycloaddition pathway is followed, whereas in
case of reactions with monophenyl and monochloroketene
[4+2] cycloaddition is observed.
Aromatic C H stretching peak appeared in the region of
2980–2922 cm−1. The >C N stretching frequencies have
been assigned to 1630–1618 cm−1 region. The phenyl
ring skeletal (>C C<) vibrations appeared from 1615 to
1590 cm−1. The absorption bands from 685 to 660 cm−1
and 595 to 580 cm−1 have been attributed to C Cl and
C Br stretching vibrations, respectively.
In the PMR spectra of compounds (1), methine proton at
C‐5 position of thiazole moiety appeared as a sharp singlet
at δ 6.6–6.7 ppm. A broad singlet was observed in the re-
gion of δ 2.1–2.4 ppm due to NH2 protons which was
D2O exchangeable. Aromatic protons were observed as a
multiplet from δ 6.91–7.72 ppm.
In the 1H‐NMR spectra of 2‐arylideneamino‐4‐
arylthiazoles (azomethine) (2), disappearance of NH2
protons and appearance of new N CH proton resonance
signal as a sharp singlet at δ 5.04–5.88 ppm was
observed. This downfield shift confirmed the conversion
of amino group ( NH2) into imino group ( N CH ).
Aromatic protons appeared as a complex multiplet in
the region of δ 7.00–8.26 ppm and methine proton of
thiazole moiety remained unaltered, as a singlet in the
region δ 6.67–6.90 ppm.
In the PMR spectra of 3,7‐diaryl‐6,7‐dihydro‐5H‐6‐
substituted‐thiazolo
[3,2‐a]pyrimidin‐5‐ones
(3a–j),
CH N< proton resonance signal appeared as a doublet at
δ 4.07–4.40 ppm with coupling constant J = 5.6–6.0 Hz.
A doublet due to CH–R group appeared at δ 4.25–4.82
ppm (J = 6.0–6.5 Hz). It shows disrotatory [4+2] cycload-
dition to yield the cis stereo chemical relationship with
CH N< proton. This downfield shift is attributed to elec-
tron withdrawing C O group in its vicinity. Possibility for
the formation of its regioisomer thiazolo[3,2‐a]
1
pyrimidin‐6‐ones is ruled out on the basis of H NMR
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. Gupta, D. Sharma, P. S. Verma, and A. Jain
Vol 000
Scheme 2
where 2 singlets are expected for >CH N< and >CH R
protons if this isomer is formed. The CH (methine) proton
signal of thiazole moiety appeared as a sharp singlet at δ
6.75–6.86 ppm. Aromatic protons (Ar‐H) appeared as a
complex multiplet in the region of δ 6.60–7.89 ppm.
Final confirmation was obtained from Fast Atomic Bom-
bardment (FAB) mass spectra which exhibited molecular
ion peak (M+) of the compounds 3a–j that corresponded
well with their respective molecular formulae. Tsuji [34]
studied the mass fragmentation modes of 1,3,4‐
thiadiazolo[3,2‐a]pyrimidiones to determine the position
of C O in the 5‐ones and isomeric 7‐ones and intense ions
corresponding to the loss of C O from the molecular ion. In
both these of compounds, a retro Diels‐Alder (RDA) pro-
cess was observed. This type of intense ion peak attributed
to the loss of C O, and a RDA process were also observed
in the synthesized compounds (3a–j).
pea (Cicer arietinum L.) fields in January and a larva along
with chick pea leaves was placed in a plastic container with
a perforated lid (10 g capacity) to avoid cannibalism. The
stock culture was maintained.
A test solution was made by dissolving the compound in
1–2 mL of acetone, then adding water to make up the vol-
ume upto 1 L. Two doses of 0.05% and 0.025% were se-
lected for innoculation. For control, only acetone and
water mixture was used. For comparison a standard
0.05% solution of endosulfan was also prepared in a simi-
lar 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 concentration
of each compound. A total of 2–3 g of chick pea shoots
Table 1
Yield (%) and time (h) of the synthesis of 3,7‐diaryl‐6,7‐dihydro‐5H‐6‐
substituted‐thiazolo[3,2‐a]pyrimidin‐5‐ones (3a–j).
Insecticidal
activity.
Helicoverpa
armigera
(Lepidoptera; Noctuidae), the old world worm, is highly
polyphagous insect. This moth is a major pest threat
because the larva can feed on a wide range of
economically important crops including cotton, corn,
tomato, legumes, and tobacco. Polyphagy, high mobility,
high fecundity, and facultative diapauses are its key
physiological, behavioral, and ecological characteristics
that facilitate its survival even under unstable habitats.
In this study, all the synthesized compounds (3a–j) were
screened for their insecticidal activity, which was mea-
sured on third instar larvae of Helicoverpa armigera at
the Department of Entomology, Agricultural Research Sta-
tion, Durgapura, Jaipur by food dipping method [35]. The
different instar larvae were collected from the local chick
Yield (%)
Time (h)
Compound
(a)
(b)
(a)
(b)
3a
3b
3c
3d
3e
3f
3g
3h
3i
73.8
71.0
80.3
76.5
82.2
72.0
72.5
81.4
69.7
75.2
57.5
54.0
61.2
64.5
58.0
60.7
54.6
62.4
55.5
53.3
3
3
2.5
2
2
2.5
3
2
2
3
8
8.5
8
7
7.5
8
9
7
7.5
9
3j
(a) Ultrasonic irradiation.
(b) Conventional method.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014 Insecticidal Evaluation and [4+2] Aza-Diels-Alder Synthesis of 3,7-Diaryl-6,7-dihydro- 5H-
6-substituted thiazolo[3,2-a]pyrimidin-5-ones Under Coupled Ultrasonic Irradiation and PTC
Scheme 3
were soaked in solutions for 10 sec and dried for 3–4 min
at room temperature. These shoots were then introduced in
the plastic container having larvae. The percent mortality
of the larvae was recorded after 1, 3, 5, and 7 days. The
moribund insects were also considered dead.
endosulfan. These compounds have halogens in phenyl
ring or as a substituent in their structures. In general, the ef-
fects of electron‐withdrawing substituents such as halogens
are more favorable to the activity. The introduction of F on
the benzene ring increases bioactivity. By comparing the
insecticidal activities of the compound (3a–j), it was found
that their activities against Helicoverpa armigera increased
in the following order 3i > 3j > 3h > 3d > 3f > 3e > 3g
> 3a > 3b > 3c. Therefore, it can be concluded that with
the increase of electron‐withdrawing power, insecticidal
The percent figures were then converted to the angular
transformation values, which were then subjected to statis-
tical analysis of completely randomized design (CRD)
technique [36]. The results are presented in Table 2. Ini-
tially after 24 h of the treatment, all the synthesized com-
pounds showed only 40–60% mortality at 0.05 ppm and
30–40% mortality at 0.025 ppm, which is higher than the
standard endosulfan (25% mortality at 0.05 ppm). No mor-
tality was observed in untreated control. Compound 3i
shows highest bioactivity (60% mortality at 0.05 ppm
and 40% mortality at 0.025 ppm) than the other tested
compounds. After 3 days of the treatment, all tested com-
pounds showed 50–85% mortality at 0.05 ppm and 40–
60% mortality at 0.025 ppm. At this time, compound 3i
and 3j showed higher insecticidal activity than the others.
After 5 days of the experiment, all the synthesized com-
pounds (3a–j) showed good activity, 70–100% mortality at
0.05 ppm and 50–70% at 0.025 ppm even better than endo-
sulfan at same dosage level. Final observations regarding
the mortality were taken after 7 days of the treatment. All
the synthesized compounds initially were found to exhibit
low bioactivity upto 3 days, but after 5 days and 7 days
time interval, their activity increased and was at par with
the standard endosulfan compound. The results are
discussed with respect to the variation associated with the
aryl moiety and nature of substituents.
activity
of
3,7‐diaryl‐6,7‐dihydro‐5H‐6‐substituted‐
thiazolo[3,2‐a]pyrimidin‐5‐ones against old world worm
increases.
EXPERIMENTAL
All the melting points were determined in open glass capillary
tubes and are uncorrected. The IR spectra (vmax in cm−1) were re-
corded on FT IR model SHIMADZU‐8400S grating infrared
spectrophotometer in KBr pellets. PMR spectra were measured
on JEOL‐AL 300 spectrophotometer at 300 MHz using TMS as
an internal standard (chemical shift in δ ppm) CDCl3 was taken
as a solvent. The IR and PMR spectra were recorded at Depart-
ment of Chemistry, University of Rajasthan, Jaipur. The FAB
Mass spectra were recorded on JEOL SX 102/DA‐6000 mass
spectrometer/Data system using Argon/Xenon (6 kV, 10 mA) as
the FAB gas. Elentar Vario EL III automatic CHNS analyzer
was used for elemental analyses. The FAB mass spectra and
CHNS analyses were recorded at Central Drug Research Institute
(CDRI), Lucknow. Sonication was performed in a Toshcon
model SW 4 cleaner (with a frequency of 37 KHz and operating
at maximum power of 150 W). The purity of the compounds
was checked by TLC using silica gel (60–120 mesh) as adsorbent,
UV light or iodine accomplished visualization. All common re-
agents and solvents were used as obtained from commercial sup-
pliers without further purification. 2‐(N‐arylamino)‐4‐
arylthiozoles [37] (1) and 2‐N‐arylideneamino‐4‐arylthiazoles
[38] (2) were prepared by the literature methods.
The compound 3i (X = 4‐Br, Y = 4‐F, R = Cl) was found
to be the most potent at both the concentrations. The com-
pound 3j (X = 4‐Br, Y = 2‐OH, R = Cl) and 3h (X = 4‐Br,
Y = 4‐OCH3, R = Br) were at par with the compound 3i,
and these were also found better insecticide than the
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. Gupta, D. Sharma, P. S. Verma, and A. Jain
Vol 000
Table 2
Percent mortality of Helicoverpa armigera on 1, 3, 5, and 7 days after the treatment by food dipping method (3a–j).
1 Day
3 Day
5 Day
7 Day
Compound
0.05
0.05
0.025
0.05
0.025
0.05
0.05
0.025
0.05
0.05
0.025
3a
0.025
0.05
0.025
0.025
0.025
3b
3c
3d
3e
3f
3g
3h
3i
40 (39.17)
35 (36.25)
35 (36.17)
55 (47.88)
50 (45.00)
50 (45.01)
60 (50.80)
60 (50.77)
55 (47.90)
25 (29.94)
0 (4.05)
30 (33.17)
30 (33.17)
25 (29.94)
40 (39.16)
35 (36.25)
30 (33.11)
35 (36.21)
40 (39.20)
40 (39.23)
55 (47.87)
50 (44.99)
50 (45.00)
70 (56.94)
65 (53.82)
60 (50.78)
70 (56.83)
85 (67.79)
85 (53.82)
40 (39.22)
0 (4.05)
40 (39.22)
40 (39.19)
40 (39.15)
50 (45.00)
55 (47.88)
50 (45.00)
50 (45.00)
55 (47.90)
60 (50.80)
70 (56.83)
75 (60.06)
65 (53.72)
90 (71.86)
80 (63.52)
75 (60.06)
100 (85.94)
100 (85.94)
100 (85.94)
60 (50.80)
0 (4.05)
55 (47.90)
50 (45.00)
50 (45.00)
65 (53.83)
60 (53.80)
60 (50.78)
60 (50.78)
70 (56.83)
70 (56.83)
90 (71.86)
90 (71.86)
85 (67.79)
100 (85.94)
100 (85.94)
95 (77.92)
100 (85.94)
100 (85.94)
100 (85.94)
75 (60.20)
0 (4.05)
65 (53.75)
65 (53.82)
60 (50.78)
70 (56.98)
65 (53.82)
65 (53.72)
75 (60.20)
80 (63.52)
75 (60.20)
3j
Endosulfan
Control
SEm
CD 5%
CV%
1.79
5.06
9.43
1.97
5.58
8.41
1.48
4.19
5.19
1.76
4.98
5.42
CD, Critical difference.
CV, Coefficient of variance.
Figures in parenthesis are angular transformation values.
Method (a). A mixture of n‐TBAHSO4 (10 mmol, 3.39 g)
and KOH (20 mmol, 1.12 g) was grinded together in a mortar.
Then, this mixture was transferred into a 250‐mL round‐bottom
flask. To this, 2‐N‐arylideneamino‐4‐arylthiazole (2) (10 mmol)
in tetrahydrofuran (20 mL) was added. 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
occured). After 10 min, bromoacetyl chloride/chloroacetyl
chloride/phenylacetyl chloride (15 mmol) in dry THF (20 mL)
was added dropwise over a period of 1 h to generate ketene and
then further sonicated for the time period as indicated in
Table 11. The bath temperature was controlled (20–25°C) by
addition or removal of water. The progress of the reaction was
monitored by TLC using C6H6:EtOAC : 90:10 as solvent
system. Sonication was continued until starting reactants
disappeared as indicated by TLC. After the completion of the
reaction, water was added and the mixture was extracted with
CHCl3 (3 × 10 mL), dried over anhydrous sodium sulfate and
filtered. The filtrate was evaporated to dryness under reduced
pressure. Further purification was accomplished by column
chromatography using silica gel (60–120 mesh) as stationary
phase and solvents of increasing polarity as mobile phase. Pure
thiazolo[3,2‐a]pyrimidin‐5‐ones (3) were obtained in (Pet ether :
Benzene) (20:80) as yellow crystalline needles.
dried over anhydrous sodium sulfate and filtered. The filtrate
was evaporated to dryness under reduced pressure. Further
purification was achieved by column chromatography using
silica gel (60–120 mesh) as stationary phase and solvents of
increasing polarity as mobile phase. Pure thiazolo[3,2‐a]
pyrimidin‐5‐ones (3) were obtained in (Pet ether : Benzene)
(20:80) as yellow crystalline needles.
(6R,7S)‐6‐Chloro‐3,7‐diphenyl‐6,7‐dihydrothiazolo[3,2‐a]
pyrimidin‐5‐one (3a).
M.p. 198°C; IR: 3025 (aromatic
C H str.), 2925 (aliphatic C H str.), 1710 (>C O str.), 1620
(>C N str.), 1600 (aromatic C C str.), 680 (C Cl str.); 1H‐
NMR: (CDCl3): δ 6.91–7.49 (m, ArH, 10H) 4.67 (d, J =
6.0 Hz, CO CH, 1H), 4.15 (d, J = 5.6 Hz, N CH, 1H), 6.75
(s, Thiazole H, 1H); Mass spectrum (m/z): 340/342; Anal.
Calcd. for C18H13ClN2OS (340.83): C, 63.43; H, 3.84; N,
8.22; S, 9.41; found: C, 63.42; H, 3.80; N, 8.20; S, 9.39.
(6R,7S)‐6‐Bromo‐3,7‐diphenyl‐6,7‐dihydrothiazolo[3,2‐a]
pyrimidin‐5‐one (3b).
M.p. 190°C; IR: 3020 (aromatic C H
str.), 2922 (aliphatic C H str.), 1705 (>C O str.), 1618 (C N
str.), 1600 (aromatic C C str.), 586 (C Br str.); 1H‐NMR:
(CDCl3): δ 6.86–7.38 (m, ArH, 10H) 4.62 (d, J =6.0 Hz,
CO CH, 1H), 4.10 (d, J = 5.6 Hz, N CH, 1H), 6.78 (s, Thiazole
H, 1H); Mass spectrum (m/z): 384/386; Anal. Calcd. for
C18H13BrN2OS (385.28): C, 56.11; H, 3.40; N, 7.27; S, 8.32;
found: C, 56.09; H, 3.32; N, 7.25; S, 8.30.
(6R,7R)‐3,6,7‐Triphenyl‐6,7‐dihydrothiazolo[3,2‐a]pyrimidin‐
Method (b). A mixture of n‐TBAHSO4 (10 mmol, 3.39 g)
and KOH (20 mmol, 1.12g) and 2‐N‐arylideneamino‐4‐
arylthiazole (2) (10 mmol) in tetrahydrofuran (20 mL) was
stirred at room temperature (20–25°C). To this, bromoacetyl
chloride/chloroacetyl chloride/phenylacetyl chloride (15 mmol)
in dry THF (20 mL) was slowly added dropwise with constant
stirring over a period of 1 h to generate ketene. The progress of
the reaction was monitored by TLC using C6H6:EtOAC : 90:10
as solvent system. After the completion of the reaction, mixture
was quenched with water and extracted with CHCl3 (3 × 10 mL),
5‐one (3c).
M.p.195°C; IR: 3050 (aromatic C H str.), 2940
(aliphatic C H str.), 1712 (>C O str.), 1620 (C N str.), 1610
(aromatic C C str.); 1H‐NMR: (CDCl3): δ 6.96–7.80 (m, ArH,
15H) 4.25 (d, J = 6.0 Hz, CO CH, 1H), 4.07 (d, J = 5.6 Hz,
N CH, 1H), 6.80 (s, Thiazole H, 1H); Mass spectrum (m/z): 382;
Anal. Calcd. for C24H18N2OS (382.48): C, 75.37; H, 4.74; N,
7.32; S, 8.38; found: C, 75.35; H, 4.76; N, 7.30; S, 8.35.
(6R,7S)‐6‐Chloro‐7‐(4‐methoxyphenyl)‐3‐phenyl‐6,7‐dihydro
thiazolo[3,2‐a]pyrimidin‐5‐one (3d).
(aromatic C H str.), 2945 (aliphatic C H str.), 1718 (>C O str.),
M.p. 210°C; IR: 3020
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014 Insecticidal Evaluation and [4+2] Aza-Diels-Alder Synthesis of 3,7-Diaryl-6,7-dihydro- 5H-
6-substituted thiazolo[3,2-a]pyrimidin-5-ones Under Coupled Ultrasonic Irradiation and PTC
1620 (C N str.), 1595 (aromatic C C str.), 682 (C Cl str.); 1H‐
NMR: (CDCl3): δ 6.65–7.80 (m, ArH, 9H) 4.55 (d, J = 6.2 Hz,
CO CH, 1H), 4.18 (d, J = 5.8 Hz, N CH, 1H), 6.80 (s, Thiazole
H, 1H), 3.35 (s, OCH3, 3H); Mass spectrum (m/z): 427; Anal.
Calcd. for C19H15ClN2O2S (370.85): C, 61.53; H, 4.08; N, 7.55;
S, 8.65; found: C, 61.52; H, 4.05; N, 7.54; S, 8.60.
(6R,7R)‐7‐(4‐Methoxyphenyl)‐3,6‐diphenyl‐6,7‐dihydrothiazolo
[3,2‐a]pyrimidin‐5‐one (3e). M.p. 192°C; IR: 3030 (aromatic C H
str.), 2950 (aliphatic C H str.), 1722 (>C O str.), 1620 (C N str.), 1595
(aromatic C C str.), 682 (C Cl str.); 6.80–7.85 (m, ArH, 14H) 4.60 (d,
J = 6.2 Hz, CO CH, 1H), 4.27 (d, J = 5.8 Hz, N CH, 1H), 6.85 (s,
Thiazole H, 1H), 3.35 (s, OCH3, 3H); Mass spectrum (m/z): 412;
Anal. Calcd. for C25H20N2O2S (412.5): C, 72.79; H, 4.89; N, 6.79;
S, 7.77; found: C, 72.73; H, 4.84; N, 6.75; S, 7.75.
Acknowledgements. The authors wish to express their gratitude
to Dr. K. P. Madhusudanan, Deputy Director and Head, SAIF
(Sophisticated Analytical Instrument Facility), Central Drug
Research Institute (CDRI), Lucknow for elemental analyses and
spectral data. Authors also record their sincere thanks to Dr.
Swaroop Singh, Durgapura Agricultural Research Station,
Jaipur for providing necessary facilities during insecticidal
evaluation. One of the authors, Deepti Sharma is grateful to
Centre of Advanced Studies (CAS), Department of Chemistry,
University of Rajasthan, Jaipur for award of JRF and, Anshu
Jain is thankful to Malaviya National Institute of Technology,
Jaipur for financial assistantship as scholarship.
(6R,7R)‐7‐(4‐Chlorophenyl)‐3,6‐diphenyl‐6,7‐dihydrothiazolo
REFERENCES AND NOTES
[3,2‐a]pyrimidin‐5‐one (3f).
M.p. 210°C; IR: 3040 (aromatic
C H str.), 2930 (aliphatic C H str.), 1720 (>C O str.), 1622 (C N
str.), 1615 (aromatic C C str.), 685 (C Cl str.); 1H‐NMR: (CDCl3):
δ 6.60–7.78 (m, ArH, 14H) 4.62 (d, J = 6.2 Hz, CO CH, 1H),
4.30 (d, J = 5.9 Hz, N CH, 1H), 6.82 (s, Thiazole H, 1H); Mass
spectrum (m/z): 416/418; Anal. Calcd. for C24H17ClN2OS
(416.92): C, 69.14; H, 4.11; N, 6.72; S, 7.69; found: C, 69.11; H,
4.10; N, 6.70; S, 7.65.
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1
(C N str.), 1615 (aromatic C C str.); H‐NMR: (CDCl3): δ 6.94–
7.85 (m, ArH, 14H) 4.55 (d, J = 6.4 Hz, CO CH, 1H), 4.10 (d,
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(6R,7S)‐6‐Bromo‐3‐(4‐bromophenyl)‐7‐(4‐methoxyphenyl)‐
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1
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46.18; H, 2.86; N, 5.67; S, 6.49; found: C, 46.14; H, 2.84; N,
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(6R,7S)‐3‐(4‐Bromophenyl)‐6‐chloro‐7‐(4‐fluorophenyl)‐6,7‐
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M.p. 220°C; IR:
3055 (aromatic C H str.), 2973 (aliphatic C H str.), 1725
(>C O str.), 1625 (C N str.), 1615 (aromatic C C str.), 1195
(C F str.), 660 (C Cl), 580 (C Br); 1H‐NMR: (CDCl3): δ 6.95–
7.82 (m, ArH, 7H) 4.77 (d, J = 6.4 Hz, CO CH, 1H), 4.38
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IR: 3040 (aromatic C H str.), 2980 (aliphatic C H str.), 1720
(>C O str.), 1630 (C N str.), 1612 (aromatic C C str.), 670
(C Cl str.), 585 (C Br); 1H‐NMR: (CDCl3): δ 6.80–7.73 (m,
ArH, 7H) 4.82 (d, J = 6.5 Hz, CO CH, 1H), 4.40 (d, J = 6.0
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