Synthesis, characterization, and biological activity of phosphorylated/thiophosphorylated compounds of 2-substituted benzimidazoles

Article abstract of DOI:10.1002/hc.20385

A series of phosphorylated and thiophosphorylated compounds of 2-substituted benzimidazoles have been synthesized by the reaction of POCl ₃ and PSCl₃ with 2-substituted benzimidazoles in different molar ratios. The compounds have been characterized by elemental analyses, infrared, and ¹H NMR and ³¹P NMR spectral studies. These compounds were found to be insecticidal when tested against Periplenata americana.

Full text of DOI:10.1002/hc.20385

Heteroatom Chemistry
Volume 19, Number 2, 2008
Synthesis, Characterization, and Biological
Activity of Phosphorylated/Thiophosphorylated
Compounds of 2-Substituted Benzimidazoles
Sonu Pareek,1 Sushma Vyas,2 G. Seth,1 and P. C. Vyas1
1Department of Chemistry, University of Rajasthan, Jaipur 302 004, India
2Government P.G. College, Kaladera, Rajasthan, India
Received 9 November 2005; revised 9 May 2006
compounds containing heterocyclic moiety increase
ABSTRACT: A series of phosphorylated and thio-
the protonation at the site of action of pesticides and
phosphorylated compounds of 2-substituted benzim-
enhance their biological activity.
idazoles have been synthesized by the reaction of
Taking this into consideration and in con-
POCl3 and PSCl3 with 2-substituted benzimidazoles
tinuation of our work on benzazolyl-synthesized
in different molar ratios. The compounds have been
organophosphorus pesticides [11–13], we have
1
characterized by elemental analyses, infrared, and H
synthesized phosphoroamidates and phosphoroth-
NMR and 31P NMR spectral studies. These compounds
ioamidates by reacting 2-substituted benzimidazoles
were found to be insecticidal when tested against
with POCl3/PSCl3. A schematic presentation is given
ꢀ
C
Periplenata americana.
2008 Wiley Periodicals, Inc.
in Scheme 1.
Heteroatom Chem 19:154–157, 2008; Published online
in Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.20385
RESULTS AND DISCUSSION
The results of IR spectral studies have been summa-
rized in Table 1. IR spectra of compound 1a showed
absorption bands at 3400–3200 cm−1 assigned to
aminophenyl ring. In IR spectra of compounds 1a–
4b, two absorption bands in the region 3150–3300
cm−1 and 1420 cm−1 were assigned to NH stretch-
ing and bending vibrations of imidazolyl ring, re-
spectively [14]. This confirmed the nondeprotona-
tion of imidazolyl proton during phosphorylation
and thiophosphorylation reactions.
INTRODUCTION
Organophosphorus compounds possess significant
insecticidal, acaricidal, and fungicidal properties
[1–4]. Organophosphorus compounds exert their bi-
ological action on arthropods by attacking the neural
transmission system and inhibiting the function of
enzyme acetylcholinesterase (AchE) [5,6]. Literature
survey [7–10] has revealed that organophosphorus
In IR spectra of derivatives 2a,b–4a,b, two
strong absorption bands at 2990 −and 2800 cm−1
were also observed. The presence of these twin fre-
quencies confirmed the formation of P NH (aryl)
bond by the removal of proton from 2-substituted
NH2 group during phosphorylation reactions [15].
This was further supported by the presence of ab-
sorption band of medium intensity at 650 cm−1
This paper was presented at the International Conference Sus-
tainable Development and Resource Utilization: Current Trends
and Perspectives, held at University of Rajasthan, Jaipur, India,
September 23–25, 2005.
Correspondence to: Sonu Pareek; e-mail: sonu90@hotmail.com.
Contract grant sponsor: State Department of Science and Tech-
nology.
c
ꢀ
2008 Wiley Periodicals, Inc.
154

Synthesis, Characterization, and Biological Activity of Phosphorylated/Thiophosphorylated Compounds 155
served at 4.9–5.0 ppm due to NH (aryl) protons. All
these chemical shift values were observed in nearly
same region as described by Black and Heffernan
[16]. The results of study are given in Table 2. 31P
NMR spectra of these derivatives show signal reso-
nance in the region δ 63.5–75.1 ppm, which indicates
the purity of these compounds.
EXPERIMENTAL
Melting points were determined in open cap-
illaries and are uncorrected. IR spectra (KBr)
were recorded on a Perkin Elmer 577 grating IR
spectrophotometer.
1
The H NMR spectra (chemical shifts in δ ppm)
were obtained from FX90Q Jeol type spectropho-
tometer at 90 MHz using TMS as an internal refer-
ence. The purity of all the compounds were checked
by running TLC on silica gel G plates, using pet
ether–methanol mixture and visualizing spots by
iodine vapors.
Synthesis of 2-Substituted Benzazole Derivatives
2-(2’-Aminophenyl)benzimidazole (1a) (mp 219◦C)
was prepared by reacting orthophenylenediamine
(OPD) with anthranillic acid in freshly prepared
polyphosphoric acid (PPA). Reactions were carried
out according to the procedure described by Heins
et al. [17] and modified by Vyas et al. [18].
SCHEME 1
Synthesis of Phosphorylated and
Thiophosphorylated Derivatives
Phosphorylated derivatives were prepared in strict
inert atmosphere. Dry nitrogen gas was flushed con-
tinuously during the reaction tenure.
that was assigned to P N stretching vibrational fre-
quency.
IR spectra of derivatives 2a, 3a, and 4a showed
a broad absorption band at 1220–1240 cm−1, as-
signed to P O stretching vibrations. Two absorp-
tion bands at 700 and 670 cm−1 in derivatives 2b,
3b, 4b were assigned for P S (I) and P S (II) vi-
brations, respectively. The presence of P Cl bond
(2a,b–3a,b) was supported by the appearance of ab-
sorption bands at 510 and 580–585 cm−1 due to P Cl
symmetric and asymmetric stretching vibrations, re-
spectively. Other absorption frequencies observed
were assigned to stretching and bending vibrations
of the benzimidazolyl ring.
(C13H10N3)P(O)Cl2 and (C13H10N3) P(S)Cl2. 2-
(2ꢁ-Aminophenyl) benzimidazole (0.001 mol) in dry
THF (30 mL) was taken in a flame-dried three-
necked Round Bottom (RB) flask, along with KHCO3
(0.001 mol). To this mixture, the solution of
POCl3/PSCl3 (0.001 mol) in dry THF (30 mL) was
added slowly at 0◦C with the help of a dropping fun-
nel. This mixture was refluxed with continuous stir-
ring for about 14 h. After checking the completion of
reaction by TLC, the product was isolated by filter-
ing through a closed sintered funnel to remove KCl
formed as a by-product during the reaction. The fil-
trate was concentrated to 1/4th of its volume under
reduced pressure and kept overnight in a vacuum
desiccator to obtain crystals.
In 1H NMR spectra of derivatives 1a–4b, a broad
singlet was observed around 8.2–8.6 ppm due to
NH (imidazolyl) proton, showing its nondeproto-
nation. Aromatic protons appear as a complex mul-
tiplet in the region δ 7.2–8.2. A doublet signal was ob-
Heteroatom Chemistry DOI 10.1002/hc

156 Pareek et al.
TABLE 1 IR Spectral Data (in cm−1) of Phosphorylated and Thiophosphorylated Derivatives of 2-Substituted Benzimidazole
Derivatives
Compounds
νas NH
δ NH
νas NH2
P NH C (aryl)
P O/P S
P–Cl
1a
2a
3150–3050
2960
2870
2980
2870
2960
2850
2985
2890
2990
2870
2960
2850
1420
1410
3400
–
–
650
–
–
1250
510 (sym.)
585 (asym.)
510 (sym.)
600 (asym)
515 (sym)
2b
3a
3b
4a
4b
1410
1410
1420
1410
–
–
–
–
–
–
1030
670
1040
660
800 (I)
700 (II)
1230
650
800(I)
690(II)
1220
510 (sym)
650
670
–
–
800 (I)
700 (II)
TABLE 2 Proton NMR and 31P NMR Spectra (δ, ppm) of Phosphorylated/Thiophosphorylated Derivatives of 2-Substituted
Benzimidazoles
1H NMR
Compounds
NH (imidazolyl)
NH2 (aryl)/ NH (aryl)
Aromatic
31P NMR
1a
2a
3a
4a
5a
6a
7a
8.4 (bs)
8.4 (s)
8.5 (s)
8.6 (s)
8.6 (s)
8.5 (s)
8.5 (s)
5.2 (s)
5.4 (d)
5.1 (d)
4.9 (d)
5.2 (d)
5.0 (d)
5.0 (d)
6.9–7.8 (m)
7.4–8.0 (m)
7.0–7.8 (m)
6.9–8.0 (m)
7.4–8.0 (m)
6.9–7.6 (m)
6.9–7.6 (m)
–
72.3
68.4
63.5
75.1
70.2
65.7
All values are in cm−1
.
bs = broad singlet; s = singlet; m = multiplet; d = doublet.
TABLE
3 Physical and Analytical Data of Phosphorylated and Thiophosphorylated Derivatives of 2-Substituted
Benzimidazoles
Molecular
Weight
Elemental Analysis (Calcd) Found
Calculated
(Found)
Compounds
MP ( ◦C) Yield (%)
Color
C
H
N
P
–
Cl
–
S
–
–
1a
2a
2b
3a
209
(219)
326
(321)
342
(348)
499
(501)
515
(510)
671
(664)
687
214
218
230
223
217d
220
217d
82
78
75
80
76
75
77
White
crystals
Light
(74.69) (5.29) (20.08)
74.24 5.12 19.98
(47.85) (3.06) (12.88) (9.50) (21.77)
47.91 3.14 12.93 9.53 21.81
(45.61) (2.92) (12.28) (9.06) (20.76) (9.35)
yellow
Yellowish
white crystals
Light
brown crystals
Brown
45.72
2.96
12.42
9.08
20.71
(7.11)
7.22
(6.89)
6.78
–
9.30
–
(62.52) (4.00) (16.83) (6.21)
62.22
(60.58) (3.88)
60.70 3.89
3.95
16.95
(16.3)
15.90
6.30
(6.01)
5.89
3b
4a
4b
(6.21)
6.32
–
crystals
Yellow
crystals
Yellow
(69.70) (4.47) (18.77) (4.61)
69.86
(68.12) (4.36)
67.78 4.48
4.55
18.89
(18.3)
18.12
4.68
(4.51)
4.69
–
(4.65)
4.73
(679)
crystals
Molecular weights are in whole numbers.
d = decomposed.
Heteroatom Chemistry DOI 10.1002/hc

Synthesis, Characterization, and Biological Activity of Phosphorylated/Thiophosphorylated Compounds 157
TABLE 4 Insecticidal Activity of Phosphorylated and Thiophosphorylated Derivatives of 2-Substituted Benzimidazoles
Mortality (%)
24 h
40
48 h
72 h
40
20
60
20
40
60
20
60
(µgm/cm2) (µgm/cm2) (µgm/cm2) (µgm/cm2) (µgm/cm2) (µgm/cm2) (µgm/cm2) (µgm/cm2) (µgm/cm2)
1a
2a
2b
3a
3b
4a
4b
14
42
40
52
48
48
46
18
46
44
60
56
54
52
20
50
52
64
58
58
56
16
46
46
54
54
52
50
22
50
48
62
62
56
56
24
–
54
68
66
60
58
–
46
–
60
58
54
54
26
56
52
62
60
56
56
26
–
56
70
66
60
58
(C13H10N3)2P(O)Cl and (C13H10N3)2P(S)Cl. 2-(2ꢁ-
REFERENCES
Aminophenyl) benzimidazole (0.002 mol) and
KHCO3 (0.002 mol) were taken in a three-necked RB
flask, and to this mixture a solution of POCl3/PSCl3
(0.001 mol) was added slowly at 0◦C. The mix-
ture was refluxed for about 15 h. Same procedure
was applied to obtain the product as described
above.
[1] Walsch, E. N.; Griffith, E. J.; Parry, R. W.; Quin, L. D.
Phosphorus Chemistry; American Chemical Society:
Washington, DC, 1992.
[2] lorish, V. Yu.; Grachev, M. K.; Bekker, N. R.; Nifantev,
E. G. Zh Obshch Khim 1993, 63, 783.
[3] Sengupta, S. K.; Pandey, O. P.; Rao, G. P.; Diwivedi,
A.; Singh, P. Phosphorus Sulphur Silicon 2003, 178,
839.
[4] Sengupta, S. K.; Pandey, O. P.; Rao, G. P.; Vishen, P.
Metal Based Drugs 2002, 8, 293.
[5] Fest, C.; Schmidt, K. J. Chemistry of Organophos-
phorus Compounds; Springer-Verlag: Berlin, 1973.
[6] Theissen, P. J. Pesticide Chemistry; Boyle, Y. P.;
Fujita, T. (Eds.); 1983; Vol. I.
[7] Clark, V. M.; Hutchinson, D. W.; Kirbay, A. I.;
Warren, S. G. Angew Chem 1964, 78, 704.
[8] Matevosyan, G. L.; Matyushichev, I. Yu.; Vadovatova,
S. N.; Zaulin, P. M. Zh Obshch Khim 1987, 57, 1055.
[9] Matevosyan, G. L.; Matyushichev, R. H.; Vadovatova,
S. N.; Zaulin, P. M. Zh Obshch Khim 1987, 51, 775
[10] Iorish, V. Yu.; Grachev, M. K.; Bakker, N. R.;
Nifantev, E. G. Zh Obsch Khim 1993, 63, 783.
[11] Vyas, P. C.; Vyas, S.; Vyas, P.; Chahar, Y. Asian J
Chem 1993, 5, 844.
(C13H10N3)3P(O) and (C13H10N3)3P(S). 2-(2ꢁ-
Aminophenyl) benzimidazole (0.003 mol) and
KHCO3 (0.003 mol) in dry THF (30 mL) were taken
in a three-necked RB flask, and to this mixture a
solution of POCl3/PSCl3 (0.001 mol) in dry THF
(30 mL) was added slowly at 0◦C. This mixture
was refluxed for about 15 h. Product was obtained
by following the same procedure as described
above.
The results of analytical and physical studies are
given in Table 3.
Insecticidal Activity
[12] Vyas, P. C.; Kaur, N.; Vyas, S. Heterocycl Commun
1997, 3(1).
[13] Kaur, N.; Vyas, P.; Vyas, P. C. Indian J Heterocycl
Chem 1996, 6(1).
The insecticidal activity of derivatives 1a–4b was de-
termined against Periplenata americana.
[14] Bellamy, L. J. The IR Spectra of Complex Molecules,
2nd ed.; Metheum: London, 1958.
[15] Thomas, L. C. Interpretation of the IR Spectra of
Organophosphorus Compounds; Heydon: London;
1974; p. 235.
[16] Black, P. J.; Heffernan, M. L. Aust J Chem 1962, 15,
862.
[17] Hein, D. W.; Alhein, R. J.; Leawitt, J. J. J Am Chem
Soc 1957, 79, 427.
[18] Vyas, P. C.; Oza, C. K.; Goyal, A. K. Chem Ind 1980,
280.
[19] Singh, R. S. Plant Diseases, 4th ed.; Oxford and IBH
Publishing: New Delhi, 1978.
The test was performed at room temperature in
a plastic box of 10 × 10 × 12 cm3 by the contact and
topical method [19]. The percentage mortality was
recorded after 48 and 72 h. Results of test are given
in Table 4.
The inference drawn from the table revealed that
the activity of compounds increases with the in-
crease in the concentration. Compounds having P O
bond resulted in higher toxicity then compounds
having P S bond, with the same substituents at-
tached to phosphorus.
Heteroatom Chemistry DOI 10.1002/hc