Insecticidal activity of some new amidophosphoric acid esters containing substituted pyridine moieties

Article abstract of DOI:10.1080/10426500801967997

Some new amidophosphoric acid esters containing substituted pyridine moieties were synthesized by the reaction of O-aryl, O-ethyl phosphoryl chlorides with 3-(aminomethyl)pyridine and 5-(aminomethyl)-2-chloropyridine. Characterization was done by 1H NMR,

Full text of DOI:10.1080/10426500801967997

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Phosphorus, Sulfur, and Silicon
and the Related Elements
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Insecticidal Activity of Some
New Amidophosphoric Acid
Esters Containing Substituted
Pyridine Moieties
Feng-Mei Sun a & De-Qing Shi a
a Key Laboratory of Pesticide and Chemical Biology
of Ministry of Education, College of Chemistry ,
Central China Normal University , Wuhan, P. R.
China
Published online: 27 Sep 2008.
To cite this article: Feng-Mei Sun & De-Qing Shi (2008) Insecticidal Activity of
Some New Amidophosphoric Acid Esters Containing Substituted Pyridine Moieties,
Phosphorus, Sulfur, and Silicon and the Related Elements, 183:10, 2615-2620, DOI:
10.1080/10426500801967997
To link to this article: http://dx.doi.org/10.1080/10426500801967997
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Phosphorus, Sulfur, and Silicon, 183:2615–2620, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500801967997
Insecticidal Activity of Some New Amidophosphoric Acid
Esters Containing Substituted Pyridine Moieties
Feng-Mei Sun and De-Qing Shi
Key Laboratory of Pesticide and Chemical Biology of Ministry of
Education, College of Chemistry, Central China Normal University,
Wuhan, P. R. China
Some new amidophosphoric acid esters containing substituted pyridine moieties
were synthesized by the reaction of O-aryl,O-ethyl phosphoryl chlorides with 3-
(aminomethyl)pyridine and 5-(aminomethyl)-2-chloropyridine. Characterization
1
1
was done by H NMR, 31P{ H} NMR, IR, MS, and elemental analyses. The results
of preliminary bioassay showed that the new compounds possess good insecticidal
activity against aphides.
Keywords Amidophosphoric acid esters; insecticidal activity; substituted pyridine
INTRODUCTION
Insecticides that have the structure and mechanism similar to nico-
tine are called neonicotinoids.1 Seven neonicotinoids such as imid-
caloprid, acetamipyrid, and nitenpyram, which have the pyridine-like
moiety, have been commercialized and many SARs (structure-activity
relationships) for these neonicotinoids have been reported.1,2 It was
found that most of the biological active nicotinic compounds contain the
3-(aminomethyl)-pyridine moiety.3 Organic phosphorus insecticides—
especially amidophosphoric acid ester insecticides—play an impor-
tant role in pesticide industry, such as methomidophos, acephate,
phenamidphos, fosthiazate, mitemate, etc., have been commercialized;
some neonicotinoid derivatives containing phosphorus atom have been
reported.4,5 Herein, we hope to report the synthesis and insecticidal
Received 2 December 2007; accepted 25 January 2008.
This work was supported by the Natural Science Foundation of China (Grant No.
20302002), and the Scientific Research Foundation for the Returned Overseas Chinese
Scholars, Ministry of Education of China (Grant No.[2007 1108).
Address correspondence to Prof. Dr. De-Qing Shi, College of Chemistry, Central China
Normal University, Wuhan 430079, Hubei, China. Email: chshidq@yahoo.com.cn
2615

2616
F.-M. Sun and D.-Q. Shi
SCHEME 1
activity of amidophosphoric acid esters containing substituted pyridine
moieties.
The synthetic route is shown in Scheme 1. Characterization was done
1
by 1H NMR, 31P{ H}NMR, IR, MS, and elemental analyses. The results
of preliminary bioassay showed that the new compounds possess good
insecticidal activity against aphides.
RESULTS AND DISCUSSION
The Structures of the Title Compounds
All the products were purified by flash column chromatography on a
silica gel with a mixture of petroleum ether and acetone (4:1, v/v) as
the eluent, The structures of compounds IIa∼IIi were confirmed by 1H
1
NMR, 31P{ H}NMR, IR spectra, MS, and elemental analyses.
For 1H NMR spectra, the NH proton appears as a broad singlet with
variable chemical shifts, the NCH2 protons display as a doublet, in
some cases as a double doublet due to the coupling with phosphorus
atom and with the proton of NH. In some cases, these protons appear
with equal chemical shifts with those of OCH2 and are difficult to
be distinguished. The pyridine protons are easily differentiated from
1
the phenyl protons. The 31P{ H}NMR spectra of compounds IIa∼IIi
exhibited a singlet in the range of δ 3.0 to 3.4. Their structures were
also supported by correct elemental analysis and by the mass spectra,
which exhibited the anticipated molecular ion peaks. The IR spectra of
all compounds showed normal stretching absorption bands indicating
the existence of the N-H ( ∼ 3200 cm−1), P=O (∼1250 cm−1), P-O-C
(∼950 cm−1) moiety.

New Amidophosphoric Acid Esters
2617
Biological Activities
Compounds IIa∼IIi were tested for insecticidal activity against
aphides by dipping at various concentrations according to a previously
reported method 6. Preliminary bioassay results show that these title
compounds possess good insecticidal activity at the different dosages.
For example, compounds IIb, IId, IIh, and IIi exhibited 100% in-
hibitory rates against aphides at the dosage of 250 mg/L. Moreover,
these four compounds also showed good insecticidal activity at the low
concentration (50 mg/L). Table 1 showed that the insecticidal activity
of compounds II depended on the nature of substituent groups in the
benzene rings; compounds containing 4-chloro and 2,4-dichloro groups
displayed good insectcidal activities. However, the chloro group in the
pyridine moiety has less effect on their biological activities. Further
structure-activity relationships are under investigation. The results of
insecticidal activities are listed in Table I.
In conclusion, we synthesized some new O-aryl, O-ethyl, N-
(substitutedpyridin-methyl) amidophosphoric acid esters. The results
of the preliminary bioassays indicated that most of the title compounds
possess good insecticidal activity.
EXPERIMENTAL
Melting points were determined with a WRS-1B digital melting point
1
1
apparatus and are uncorrected. H NMR and 31P{ H} NMR spectra
were recorded with a Varian MERCURY-PLUS400 spectrometer with
TMS and 85% H3PO4 as the internal and external reference, respec-
tively, and CDCl3 as the solvent. Mass spectra were obtained with a
Finnigan TRACEMS2000 spectrometer using the EI method. IR spec-
tra were measured by a Nicolet NEXUS470 spectrometer. Elemental
analyses were performed with a Vario EL III CHNSO elementary ana-
lyzer. The reagents and solvents were available commercially and pu-
rified according to conventional methods before use. 5-(aminomethyl)-
TABLE I Insecticidal Activity of IIa∼IIi Against Aphides: (Death
Rate %)
%Dosage
IIa
IIb
IIc
IId
IIe
IIf
IIg
IIh
IIi
250 mg/L
50 mg/L
35.6
—
100
95.6
68.5
—
100
100
53.1
—
40.7
—
71.3
—
100
81.3
100
76.4

2618
F.-M. Sun and D.-Q. Shi
2-chloro-pyridine and O-aryl, O-ethyl, phosphoryl chloride I were pre-
pared according to the reported methods,7,8 respectively.
General Procedure for the Synthesis of O-aryl, O-ethyl,
N-(substitutedpyridin-methyl) Amidophosphoric Acid Esters
Compound
I (2 mmol), triethylamine (0.3 g, 3 mmol) and
dichloromethane (10 mL) were added to a 50 mL three-necked reaction
flask, after cooling to 5oC, the solution of 3-(aminomethyl)pyridine or 5-
(aminomethyl)-2-chloro-pyridine (2 mmol) in dichloromethane (5 mL)
was added dropwise slowly, the mixture was allowed to stir at room tem-
perature for 5–6 h, until the reaction was finished (monitored by TLC).
The work-up involved filtration and drying over anhydrous magnesium
sulfate, the crude product was purified by flash column chromatogra-
phy on a silica gel with a mixture of petroleum ether and acetone
(4:1, v/v) as the eluent, giving compounds IIa∼IIi as a yellow oil or
solid.
O-ethyl, O-phenyl, N-(pyridin-3-yl-methyl) amidophosphoric acid es-
ter (IIa): an orange oil, yield 73%; IR (KBr) υ: 3216 (N-H), 1560 (C=N),
1
1390–1566 (C=C), 1236 (P=O), 950 (P-O-C); { H}NMR (CDCl3, 400
MHz) δ:1.30 (t, J = 6.2 Hz, 3H, CH3), 1.72 (sb, 1H, NH), 4.08–4.16 (m,
4H, 2CH2), 7.13–7.28 ( m, 6H, Ar-H, Py-H), 7.28 (d,J = 8.4 Hz, 1H,
1
Py-H), 7.63 (d, J = 7.6 Hz, 1H, Py-H), 8.51 (s, 1H, Py-H); 31P{ H}NMR
(CDCl3, 162 MHz) δ:3.05 (s); MS (70eV) m/z (%): 294 (22.9), 292 (M+,
66.9), 263 (34.1), 245 (4.4), 183 (29.1), 107 (100), 92 (55.5 ); Anal. Calcd.
for C14H17N2O3P: C 57.53, H 5.86, N 9.58; found C 57.26, H 5.65, N 9.37.
O-ethyl, O-(4-chlorophenyl), N-(2-chloropyridin-5-yl-methyl) ami-
dophosphoric acid ester (IIb), an orange oil, yield 68%; IR (KBr) υ:
3219 (N-H), 1589 (C=N), 1393–1569 (C=C), 1233 (P=O), 955 (P-O-C);
1
{ H}NMR (CDCl3, 400 MHz) δ: 1.32 (t, J = 6.8 Hz, 3H,CH3), 1.78 (sb,
1H, NH), 4.09–4.15 (m, 4H, 2CH2), 7.08–7.28 (m, 5H, Ar-H, Py-H), 7.59
1
(d, J = 7.6 Hz, 1H, Py-H), 8.30 (s, 1H, Py-H); 31P{ H}NMR (CDCl3,
162 MHz) δ:3.03 (s); MS (70eV) m/z (%): 362 (2.2), 360 (M+, 10.5), 317
(5.3), 238 (4.3), 190 (14.0), 127 (100), 111 (41.5), 99 (86), 75 (45.5); Anal.
Calcd. for C14H15Cl2N2O3P: C 46.56, H 4.19, N 7.76; found C 46.40, H
4.31, N 7.52.
O-ethyl, O-(2-methylphenyl), N-(2-chloropyridin-5-yl-methyl) ami-
dophosphoric acid ester (IIc), an orange oil, yield 63%; IR (KBr) υ:
3211 (N-H), 1588 (C=N), 1392–1569 (C=C), 1233 (P=O), 947 (P-O-C);
1H NMR (CDCl3, 400 MHz) δ: 1.25 (t, J = 6.0 Hz, 3H, CH3), 2.21 (s,
3H, Ar-CH3), 2.60 (sb, 1H, NH), 4.07–4.10 (m, 2H,CH2), 4.13 (dd, J =
10.8 Hz, J = 7.6 Hz, 2H, CH2N), 7.03–7.58 (m, 5H, Ar-H, Py-H), 7.60

New Amidophosphoric Acid Esters
2619
1
(d, J = 8.4 Hz, 1H, Py-H), 8.28 (s, 1H, Py-H); 31P{ H}NMR (CDCl3, 162
MHz) δ:3.40 (s); Anal. calcd. for C15H18ClN2O3P: C 52.87, H 5.32, N
8.22; found C 52.94, H 5.20, N 8.17.
O-ethyl, O-(2,4-dichlorophenyl), N-(2-chloropyridin-5-yl-methyl)
amidophosphoric acid ester (IId), an orange solid, m.p. 52–53oC, yield
66%; IR (KBr) υ: 3208 (N-H), 1579 (C=N), 1392–1578 (C=C), 1240
1
(P=O), 939 (P-O-C); H NMR (CDCl3, 400 MHz) δ: 1.33 (t, J = 7.2 Hz,
3H,CH3), 4.10 (dd, J = 10.4 Hz, J = 24.4 Hz, 1H, NH), 4.18–4.22 (m,
4H,2CH2), 7.18 (d, J = 8.4 Hz, 1H, Py-H), 7.24 (d, J = 8.0 Hz, 1H,
Ar-H), 7.39–7.42 (m, 2H, Ar-H), 7.61 (d, J = 8.0 Hz, 1H, Py-H), 8.31
1
(s, 1H, Py-H); 31P{ H}NMR (CDCl3, 162 MHz) δ:3.05 (s); MS (70eV)
m/z (%): 399 (14), 396 (31.1), 394 (M+, 42.8), 359 (43.6), 330 (25.5), 284
(25.2), 205 (16.1), 140 (97.2), 125 (100), 89 (24.4), 75 (7.1); Anal. calcd.
for C14H14Cl3N2O3P: C 42.50, H 3.57, N 7.08; found C 42.09, H 3.25, N
7.19.
O-ethyl, O-(2,3,4,5,6-pentachlorophenyl), N-(2-chloropyridin-5-yl-
methyl) amidophosphoric acid ester (IIe), an orange solid, m.p. 43–
45oC, yield 73%; IR (KBr) υ: 3219 (N-H), 1580 (C=N), 1390-1566 (C=C),
1239 (P=O), 954 (P-O-C); 1H NMR (CDCl3, 400 MHz) δ: 1.25 (t, J = 5.8
Hz, 3H, CH3), 3.90–3.94 (m, 2H,CH2), 4.05 (d, J = 11.0 Hz, 2H, CH2N),
4.22 (sb, 1H, NH), 7.30 (d, J = 8.0 Hz, 1H, Py-H), 7.67 (d, J = 8.0 Hz,
1
1H, Py-H), 8.34 (s, 1H, Py-H); 31P{ H}NMR (CDCl3, 162 MHz) δ: 3.04
(s); Anal. calcd. for C14H11Cl6N2O3P: C 33.70, H 2.22, N 5.61; found C
33.61, H 2.17, N 5.78.
O-ethyl, O-(2-methylphenyl), N-(pyridin-3-yl-methyl) amidophos-
phoric acid ester (IIf): an orange oil, yield 75%; IR (KBr) υ: 3219 (N-H),
1588 (C=N), 1389–1578 (C=C), 1241 (P=O), 948 (P-O-C); 1H NMR
(CDCl3, 400 MHz) δ: 1.29 (t, J = 5.8 Hz, 3H,CH3), 3.28 (sb, 1H, NH),
4.06–4.08 (m, 2H,CH2), 4.11 (d, J = 11.0 Hz, 2H, CH2N), 7.08–7.30 (m,
5H, Ar-H, Py-H), 7.35 (d, J = 7.8 Hz, 1H, Py-H), 7.70 (d, J = 7.8 Hz, 1H,
1
Py-H), 8.55 (s, 1H, Py-H); 31P{ H}NMR (CDCl3, 162 MHz) δ: 3.05 (s);
Anal. calcd. for C15H19N2O3P: C 58.82, H 6.25, N 9.15; found C 58.71,
H 6.03, N 9.31.
O-ethyl, O-(2,3,4,5,6-pentachlorophenyl), N-(pyridin-3-yl-methyl)
amidophosphoric acid ester (IIg): an orange oil, yield 68%; IR (KBr)
υ: 3215 (N-H), 1587 (C=N), 1398–1575 (C=C), 1232 (P=O), 949 (P-O-
1
C); H NMR (CDCl3, 400 MHz) δ: 1.32 (t, J = 5.4 Hz, 3H,CH3), 1.96
(sb, 1H, NH), 3.94-3.98 (m, 2H,CH2), 4.10 (dd, J = 11.4 Hz, J = 8.0 Hz,
2H, CH2N), 7.28 (d, J = 8.2 Hz, 1H, Py-H), 7.34 (d, J = 8.2 Hz, 1H,
1
Py-H), 7.59 (d, J = 7.4 Hz, 1H, Py-H), 8.36 (s, 1H, Py-H); 31P{ H}NMR
(CDCl3, 162 MHz) δ: 3.04 (s); Anal. calcd. for C14H12Cl5N2O3P: C 36.20,
H 2.60, N 6.03; found C 36.36, H 2.44, N 5.89.

2620
F.-M. Sun and D.-Q. Shi
O-ethyl, O-(4-chlorophenyl), N-(pyridin-3-yl-methyl) amidophospho-
ric acid ester (IIh): a light yellow oil, yield 75%; IR (KBr) υ: 3225 (N-H),
1588 (C=N), 1380–1581 (C=C), 1246 (P=O), 955 (P-O-C); 1H NMR
(CDCl3, 400 MHz) δ: 1.29 (t, J = 5.4 Hz, 3H,CH3), 2.10 (sb, 1H, NH),
4.05–4.08 (m, 2H,CH2), 4.13 (dd, J = 11.6 Hz, J = 7.6 Hz, 2H, CH2N),
7.08–7.27 (m, 5H, Ar-H, Py-H), 7.58 (d, J = 7.6 Hz, 1H, Py-H), 8.47 (d,
1
J = 4.8 Hz, 1H, Py-H), 8.50 (s, 1H, Py-H); 31P{ H}NMR (CDCl3, 162
MHz) δ: 3.05 (s); Anal. calcd. for C14H16ClN2O3P: C 51.47, H 4.94, N
8.57; found C 51.59, H 5.12, N 8.40.
O-ethyl, O-(2,4-dichlorophenyl), N-(pyridin-3-yl-methyl) amidophos-
phoric acid ester (IIi): a light yellow solid, m.p. 47–48oC, yield 65%; IR
(KBr) υ: 3223 (N-H), 1587 (C=N), 1389–1568 (C=C), 1248 (P=O), 953
1
(P-O-C); H NMR (CDCl3, 400 MHz) δ: 1.31 (t, J = 5.4 Hz, 3H,CH3),
3.96 (s, 1H, NH), 4.01–4.05 (m, 2H,CH2), 4.23 (dd, J = 11.2 Hz, J = 8.0
Hz, 2H, CH2N), 7.17–7.44 (m, 4H, Ar-H, Py-H), 7.63 (d, J = 7.6 Hz, 1H,
1
Py-H), 8.50 (d, J = 7.6 Hz, 1H, Py-H), 8.53 (s, 1H, Py-H); 31P{ H}NMR
(CDCl3, 162 MHz) δ: 3.00 (s); Anal. calcd. for C14H15Cl2N2O3P: C 46.56,
H 4.19, N 7.76; found C 46.39, H 4.13, N 7.95.
Insecticidal Bioassay Method Against Aphis by Dipping
Two cucumber leaves ca. 8 cm in diameter were dipped into the distilled
water solution of the various concentrations of the test compound for
a few seconds until the leaf surface was wet. After drying, the leaves
were place on soil in a pet cup. Ten 2nd-instar larvae were released
into the cup. The cup was covered with a lid and stored at 25◦C, 50–
55% relative humidity (RH), and 14 h light/10 h dark for 5 days. The
mortality was assessed after treatment. The test was run three times,
the results were averaged, 0 means no effect, and 100% means excellent
insecticidal activity, and given as death rate in Table I.
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