Synthesis and pesticidal activities of O,O- dialkyl-N-[(4-aryl)-2- thiazolyl] phosphoramidothioates

Article abstract of DOI:10.1080/10426500701512208

Several fluorine-containing O,O-dialkyl-N-[(4-aryl)-2-thiazolyl] phosphoramidothoiates were synthesized as possible antifungal and insecticidal agents by treating appropriate 2-amino-4-aryl-thiazoles with O,O-dialkyl phosphorochloridothioates. The latter were obtained by the reaction of dry alcohol on thiophosphoryl chloride in the presence of sodium metal. Some of the synthesized compounds exhibited significant antifungal activity against Aspergillus species. In insecticidal activity, compounds possessing a methyl group along with fluorine exhibited enhanced effect. It was also noted that the activity increased with the size and branching of alkyl group. Copyright Taylor & Francis Group, LLC.

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Synthesis and Pesticidal
Activities of O,O- Dialkyl-
N-[(4-aryl)-2-thiazolyl]
Phosphoramidothioates
Renuka Jain a , Satish C. Jain a , Praveen Kumar
Goyal a & Shipra Vajpei a
a Department of Chemistry and Botany , University
of Rajasthan , Jaipur, India
Published online: 25 Sep 2007.
To cite this article: Renuka Jain , Satish C. Jain , Praveen Kumar Goyal & Shipra
Vajpei (2007) Synthesis and Pesticidal Activities of O,O- Dialkyl-N-[(4-aryl)-2-thiazolyl]
Phosphoramidothioates, Phosphorus, Sulfur, and Silicon and the Related Elements,
182:11, 2605-2610, DOI: 10.1080/10426500701512208
To link to this article: http://dx.doi.org/10.1080/10426500701512208
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Phosphorus, Sulfur, and Silicon, 182:2605–2610, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701512208
Synthesis and Pesticidal Activities of O,O-
Dialkyl-N-[(4-aryl)-2-thiazolyl] Phosphoramidothioates
Renuka Jain
Satish C. Jain1
Praveen Kumar Goyal
Shipra Vajpei
Department of Chemistry and Botany, University of Rajasthan,
Jaipur, India
Several fluorine-containing O,O-dialkyl-N-[(4-aryl)-2-thiazolyl] phosphorami-
dothoiates were synthesized as possible antifungal and insecticidal agents by treat-
ing appropriate 2-amino-4-aryl-thiazoles with O,O-dialkyl phosphorochloridoth-
ioates. The latter were obtained by the reaction of dry alcohol on thiophosphoryl
chloride in the presence of sodium metal. Some of the synthesized compounds exhib-
ited significant antifungal activity against Aspergillus species. In insecticidal activ-
ity, compounds possessing a methyl group along with fluorine exhibited enhanced
effect. It was also noted that the activity increased with the size and branching of
alkyl group.
Keywords 2-Amino-4-aryl thiazoles; fungicidal activity; insecticidal activity; O,O-
dialkyl-N-[(4-aryl)-2-thiazolyl]phosphoramidothioates.
INTRODUCTION
Biological activity of organo-phophorus esters is well known.1,2 Various
esters and thioesters of O,O-dialkyl phosphoric acid and thiophospho-
ric acid are being successfully used as agricultural and household
insecticides.3,4 Study of the structure and activity in the ester se-
ries reveals a correlation between toxicity, activity and branching of
the alkylgroup through steric and inductive effect.5 In view of these
facts, some ethyl and isopropyl analogs of the title compounds were
synthesized by treating appropriate 2-amino-4-fluoroarylthiazoles with
Received March 11, 2007; accepted May 4, 2007.
The authors wish to thank D.S.T., New Delhi for financial assistance and Dr. V. Shinde,
Rajasthan Agriculture University, Durgapura, for his help in carrying out pesticidal
activities.
Address correspondence to Satish C. Jain, Department of Botany, University of
Rajasthan, Jaipur 302004, India. E-mail: jainr 15@yahoo.co.in
2605

2606
R. Jain et al.
SCHEME 1
O,O-dialkylphosphorochloridothioates (Scheme 1). The role of fluorine
in heterocyclic compound is noteworthy in view of profound changes
which are produced in biological activities on introduction of fluorine.6
Some of the compounds have been found to exhibit significant insecti-
cidal and antifungal activity.
EXPERIMENTAL
Melting points were taken in open capillary tubes using an elec-
trical apparatus and are uncorrected. Infrared spectra (νmax cm−1
)
were recorded on a Perkin-Elmer spectrophotometer as potassium
bromide pellets. Proton and phosphorus-magnetic resonance spectra
were recorded at 89.99 MHz and 36.23 MHz, respectively, on a JEOL
(model FX-90Q) machine using hexadeutero dimethylsulfoxide as sol-
vent. Chemical shifts (δ) are in parts per million downfield to the in-
ternal standard tetramethylsilane (TMS). The purity of the compounds
was checked on silica gel G plates using iodine vapours as the detecting
agent.
Synthesis of 2-Amino-4-aryl-thiazole (1) and O,O-Dialkyl
Phosphorochlorido-thioates (2)
These compounds were prepared according to the published
procedure.7,8
Synthesis of O,O-Diethyl-N-[(4-phenyl)-2-thiazolyl]-
phosphoramidothioate (3a)
To an ice cold ethereal solution of O,O-dialkyl phosphorochloridothioate
(5.6 g, 30 mmol) was gradually added with stirring an ethereal solution
(50 cc) of 2-amino-4- Phenyl-thiazole (10.5 g, 60 mmol), the mixture
was then kept at 0◦C for 24 h. The solid that separated out was washed

Social Reflection
2607
several times with cold water to remove the amine hydrochloride. The
residual mass was extracted with ether and this was mixed with the
original ether solution. After removing ether the compound was ob-
tained as a red coloured solid, which was recrystallized with pet. ether
: benzene (1:3).
Compounds 3b–k were prepared in a similar manner.
RESULTS AND DISCUSSION
The structure of synthesized compounds were established by analytical
and spectral studies. Elemental and physical data of the synthesized
compounds are given in Table I.
Infrared Spectra
The infrared spectrum of 1 showed a doublet at 3180 cm−1 and
3200 cm−1due to –NH2, its conversion to 3 was confirmed by the
TABLE I New O,O-Dialkyl-N-[(4-aryl)-2-thiazolyl]-
phosphoramidothioates
Analysis (%)
Found (Calcd.)
Substituents
R1
M.P.
(◦C)
Yield Molecular
(%) formula
Compound
R
N
S
3a
C2H5
H
145
211
70 C13H17N2O2PS2
68 C13H16FN2O2PS2
67 C14H18FN2O2PS2
8.58
19.50
(8.53) (19.51)
8.05 18.50
(8.09) (18.49)
7.75 17.72
(7.77) (17.77)
7.73 17.76
(7.77) (17.77)
3b
3c
3d
3e
3f
C2H5
4-F
C2H5
4-F, 3-CH3 95–97
C2H5
2-F, 5-CH3 116–18 74 C14H18FN2O2PS2
C2H5
4-F, 3-Cl
4-F, 2-Cl
H
160
120
97
72 C13H15ClFN2O2PS2 7.32
16.80
(7.35) (16.81)
C2H5
71 C13H15ClFN2O2PS2 7.36
16.82
(7.35) (16.81)
3g
3h
3i
CH(CH3)2
75 C15H21N2O2PS2
80 C15H20FN2O2PS2
69 C16H22FN2O2PS2
7.85
(7.86) (17.97)
7.45 17.10
(7.48) (17.11)
7.20 16.52
(7.21) (16.49)
155–57 74 C15H19ClFN2O2PS2 6.63 15.12
(6.62) (15.14)
17.96
CH(CH3)2 4-F
93–94
CH(CH3)2 4-F, 3- CH3 86–88
3j
CH(CH3)2 4-F, 3-Cl
CH(CH3)2 4-F, 2-Cl
3k
104–6
81 C15H19ClFN2O2PS2 6.68
15.11
(6.62) (15.14)

2608
R. Jain et al.
disappearance of doublet and appearance of a broad band from 3360–
3100 cm−1 for >N–H group and an additional absorption band from
760–730 cm−1 for P=S.
1H NMR Spectra
The PMR spectrum indicated the formation of compounds 3 where
a quartet in the region δ 3.25–3.80 (-CH2-) and triplet from δ 1.31–
1.37 (-CH3) in compounds 3a-f and a doublet in the region δ 1.03–1.37
[-CH(CH3)2] and a multiplet from δ 3.88–4.70 (-CH(CH3)2] in com-
pounds 3g–k appeared due to the alkoxy groups. The broad singlet ≈ δ
7.70 which disappeared on deutration indicated the conversion of –NH2
group to >NH. The other peaks observed were the aromatic protons as
a multiplet from δ 7.39–7.68 and an additional singlet in the region δ
2.14–2.30 in compounds 3c,d,i due to –CH3 group attached to phenyl
ring.
31P NMR Spectra
The 31P NMR spectrum of compounds also supported the conversion of
1 to 3. In compounds 3a–f, a singlet appeared at δ 61.17–62.17, and
in compounds 3g–k, the signal appeared at δ 53.17–55.74—due to a
pentavalent phosphorus attached to sulfur, nitrogen and, oxygen.
Pesticidal Activity
The synthesized compounds were tested for antifungal and insecticidal
activities.
Antifungal Activity Test
The antifungal activity was determined against Aspergillus flavus, A.
niger, Curvularia lunata and Fusarium moniliformae by using the filter
paper disc method of Gould and Bowie.9 Standard size (5-mm diameter)
blank Whatman filter paper discs were , sterilized by dry heat at 140◦C
for 1 h; then they were saturated with the test solution (100 µg disc−1
)
and a known quantity of standard reference (mycostatin 10 µg disc−1),
separately. These were air-dried at room temperature to remove any
residual solvent, which might interfere with the determination. The
discs were placed on the surface of a sterilized agar nutrient medium
that had been inoculated with the test organism (using a sterile swab)
and dried to remove the surface moisture. The thickness of agar medium
was kept equal in all petri plates and a standard disc was used in each

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2609
plate as a control. Before incubation, the petri dishes were placed in
a cold room (5◦C ) for 1 h to allow diffusion of the compounds from
the disc in to the agar plates. These were incubated at 37◦C for 20–24
h, after which zones of inhibition or depressed growth could be easily
measured. All experiments were in five replicates and the values were
then computed. The results are given in Table II.
It is observed that, in general, the compounds were more active
against Aspergillus species, with compounds 3e and 3g exhibiting ac-
tivity comparable to that of mycostatin and compound 3c having fluoro
and methyl group attached to phenyl ring exhibiting much higher ac-
tivity than the standard (AI = 1.27).
Insecticidal Activity Test
The insecticidal activity was evaluated against the larvae of Plutella xy-
lostella (Diamond black moth) which were reared on cauliflower leaves
using leaf feeding and direct contact method (Table II). The larvae in the
penultimate instar were selected to carry out the tests. Three batches
of ten insects each were used in each method.
TABLE II Antifungal and Insecticidal Activity of O,O-Dialkyl-N-
[(4-aryl)-2-thiazolyl]phosphoramidothioates
Test compound
Test organism
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
Antifungal activity
Aspergillus flavus
c
IZa
8
9
—
—
14
—
—
—
—
—
—
7
12
10
12
7
7
10
AIb 0.72 0.81
1.09 0.90 1.09 0.63 0.63 0.90
8
0.72 0.62 0.90 0.63
8
0.72 0.54 0.81 0.54
8
A. niger
IZ
7
7
7
10
7
—
—
—
—
7
8
0.72
—
—
8
AI 0.63 0.63 1.27
C. lunata
IZ
AI 0.72
IZ 10
8
—
—
7
7
0.63
—
6
9
6
F. moniliformae
—
—
—
—
—
—
AI 0.98 0.63
—
0.63 0.72
0.63 0.72
Insecticidal activity
(% mortality)
P. xylostella
d
∗
∗
D.C. 20
L.F. 40
40
50
80
60
40
40
∗
10
40
20
60
50 100
70 80
∗
IZa: Inhibition zone (m.m.); AIb: Activity index = Inhibition zone of
d
sample/Inhibition zone of standard; -c: Not measurable activity; ∗ : Activity not
detected; D.C.: Direct contact method ; Standard mortality 100%; and L.F.: Leaf feeding
method; Standard mortality 90%.

2610
R. Jain et al.
Leaf Feeding Method
1000 ppm solution of the compound was prepared in 5% ethyl alcohol.
Fresh cabbage/cauliflower leaves were taken, each of which was dipped
in the solution of the test sample and allowed to dry. The leaves were put
in the petri plates and ten larvae of Plutella sp. were released in each
of them. A control was also taken. Monocrotophos (50 ppm) solution
was used for standard evaluation. The larvae were left undisturbed
under laboratory condition and observations were taken after 78 h of
exposure.
Direct Contact Method
In this method 1000 ppm solution of measured quantity was sprayed
on the larvae of Plutella sp. and allowed to dry. These larvae were then
left undisturbed in petri plates along with the food material. Monocro-
tophos (50 ppm) solution was used as control. Observations were made
after 78 h.
It was observed that compounds 3a and 3f were totally inactive,
whereas 3b and 3g exhibited slight activity, showing that introduction
of fluorine brings about a positive change. Promising activity was exhib-
ited by compound 3c and 3i by both methods indicating that presence
of methyl group at 3-position with fluorine increased the activity. Com-
pound 3i showed maximum activity nearing to that of standard in both
cases indicating that the activity increases with the size and branching
of alkyl group.
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