Synthesis and insecticidal activity of nitenpyram analogs with tetrahydropyrimidine fixed (z)-configuration

Article abstract of DOI:10.1002/jhet.1558

Two series of novel (Z)-nitenpyram analogs 2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h, 3a, 3b, 3c, 3d were synthesized by introducing various amino acids benzyl ester or amino acids tetrahydrofurfur-2-yl ester into nitenpyram and forming a tetrahydropyrimidine ring to fix (Z)-configuration. The structures of the target compounds were characterized by ¹HNMR, MS, IR, and elemental analysis. Preliminary bioassays against Nilaparvata lugens indicated that all the nitenpyram analogs exhibited good insecticidal activity at 100 mg/L, whereas the compounds 3b and 3d afforded the best in vitro inhibitory activities that had ≥ 90% mortality at 20 mg/L.

Full text of DOI:10.1002/jhet.1558

Month 2013
Synthesis and Insecticidal Activity of Nitenpyram Analogs with
Tetrahydropyrimidine Fixed (Z)-Configuration
Chuan-wen Sun, Ting Fang, Zhi-bing Hao, Chun-cheng Pang, Xiao Xu, and Hua-jia Xin
a
a
a
a
a
b
*
aCollege of Life and Environment Sciences, Shanghai Normal University, Shanghai 200234, China
bBioassay department, Branch of National Pesticide R&D South Center, Hangzhou 310023, China
*
E-mail: willin112@163.com
Received August 8, 2011
DOI 10.1002/jhet.1558
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
Two series of novel (Z)-nitenpyram analogs 2a–2h, 3a–3d were synthesized by introducing various amino
acids benzyl ester or amino acids tetrahydrofurfur-2-yl ester into nitenpyram and forming a tetrahydropyrimidine
ring to fix (Z)-configuration. The structures of the target compounds were characterized by 1HNMR, MS, IR, and
elemental analysis. Preliminary bioassays against Nilaparvata lugens indicated that all the nitenpyram analogs
exhibited good insecticidal activity at 100 mg/L, whereas the compounds 3b and 3d afforded the best in vitro
inhibitory activities that had ≥90% mortality at 20 mg/L.
J. Heterocyclic Chem., 00, 00 (2013).
INTRODUCTION
It is well-known that the structure optimization of com-
mercial neonicotinoids is one of the effective resistance-
management tactics [7–9]. Until recently, most of the
researches [10–14] about structure optimization of NNSs
are on the basis of imidacloprid, although very few studies
had appeared about nitenpyram (Fig. 1) in the literature.
In our previous work [15,16] (Fig. 2), two series of
(Z)-configuration nitenpyram analogs were synthesized
with good insecticidal activities against Nilaparvata
lugens at high dose. However, in order to find more
neonicotinoids compounds with novel structural features
and broad insecticidal spectrum, two series of novel (Z)-
configuration nitenpyram analogs were synthesized, and
most of the analogs exhibited higher insecticide activities
against Nilaparvata lugens at 100 mg/L.
In the past 30 years, the discovery of neonicotinoid
insecticides (NNSs) can be considered as a milestone in
the agricultural chemical field. NNSs, which act agonisti-
cally on the insect nicotinic acetylcholine receptors
(nAChRs), are gaining widespread use as a way to control
pests, because of their high potency, low mammalian toxic-
ity, and broad insecticidal spectra [1,2]. Neonicotinoids are
increasingly used in crop protection and animal health care
because of the decrease in effectiveness of organophospho-
rus and carbamate derivatives. However, significant
increases in resistance and cross-resistance were observed
in a range of species after frequent applications [3–6].
Hence, the development of new neonicotinoids with novel
structures and high insecticidal activities against resistance
strains is highly desirable.
Motivated by the aforementioned views, starting from
nitenpyram, various amino acids were introduced and benzyl
© 2013 HeteroCorporation

C.-W. Sun, T. Fang, Z.-B. Hao, C.-C. Pang, X. Xu, and H.-J. Xin
Vol 000
of the analogs exhibited better activities than the others with
phenyl (2a vs 2e, 3a vs 3c). What is more, the analogs 2 and
3 exhibited equivalent activities at high dose (500 and
100 mg/L); however, the insecticidal activities of the analogs
2 showed much less activity when the dose was reduced to
20mg/L(3b vs 2d, 3d vs 2h). The results may be related to
the flexible linkage at 1-position of tetrahydropyrimidine.
When different optical activity amino acid esters were
introduced to the analogs 2(n = 0,2a–2h), their insecticidal
activities increased in the order methyl (2a) < isopropyl (2b)
MeS-ethyl (2c) < sec-butyl(2d) or methyl (2e) < isopropyl
(2f) < MeS-ethyl (2g) < sec-butyl(2h), which indicated that
the length and flexibility of the substituent R1 maybe
strongly related to their insecticidal activities.
In summary, two series of novel nitenpyram analogs
2a–2h, 3a–3d were synthesized by introducing different
amino acids benzyl ester or amino acids tetrahydrofurfur-
2-yl ester into nitenpyram and forming a tetrahydropyrimidine
ring to fix (Z)-configuration. Bioassay against N. lugens
showed that all the analogs had 100% mortality at
500 mg/L, and all of them had ≥ 90% mortality at
100 mg/L, the analogs 3b and 3d afforded the best
activities that had ≥ 90% mortality at 20 mg/L.
Figure 1. The structure of nitenpyram. [Color figure can be viewed in the
online issue, which is available at wileyonlinelibrary.com.]
ester or tetrahydrofurfur-2-yl ester groups were applied, two
series of novel nitenpyam analogs 2a–2h, 3a–3d with the
(Z)-configuration described herein were synthesized
(Scheme 1). The structures of the target compounds were
well characterized by 1HNMR, MS, IR, and elemental
analysis. A preliminary bioassay against N. lugens showed
that all nitenpyram analogs exhibited good insecticide
activities at 500 and 100 mg/L, and the analogs 3b and 3d
showed the best activity at 20 mg/L.
RESULT AND DISCUSSION
Synthesis.
Synthesis procedures for the novel
nitenpyram analogs 2a–2h, 3a–3d are shown in Scheme 1.
A two-step synthetic strategy was adopted to prepare the
target compounds. According to the procedures given in
the literatures[17], various amino acids were converted to
their benzyl ester hydrochloride or tetrahydrofurfur-2-yl
ester hydrochloride (intermediates 1). The target nitenpyram
analogs 2a–2h, 3a–3d were prepared by the Mannich
reaction of nitenpyram, formaldehyde, triethylamine, and
intermediates 1 in ethanol at 65ꢀC under microwave
irradiation (Scheme 1), which was a high efficient way with
good yields (66–76%) and easily post-treatment. The power
rating of microwave reactors is 1000–1050 w. The
structures of the target compounds were well characterized
by 1HNMR, MS, IR, and elemental analysis.
Insecticidal activities. The insecticidal activities of these
novel nitenpyram analogs were evaluated against N. lugens
according to the standard test [18,19]with a slight modification.
The insecticidal activities of the analogs 2a–2h, 3a–3d
were listed in Table 1. All of the analogs had 100% mortal-
ity at 500 mg/L, and all of them had ≥ 90% mortality at
100 mg/L. Among these analogs, 3b and 3d afforded the
best in vitro inhibitory activities and had ≥90% mortality
at 20 mg/L. As indicated in Table 1, in general, when the
substituent R2 is tetrahydrofurfuryl, the insecticidal activities
EXPERIMENTAL
Reagents and general methods.
Unless otherwise noted,
reagents and solvents were used as received from commercial
suppliers. All compounds are yellow or brown oil. ESI mass
spectra were obtained on an HP-5998A-high performance
liquid chromatography-mass spectrometer-computer. ESI Mass
spectra were obtained on a Waters MicroMass LCT liquid
chromatography-mass spectrometer-computer. Elemental analysis
was performed with a Perkin-Elmer 2400 instrument. IR spectra
were obtained on a Nicolet 5DX FT-IR spectrophotometer in the
region of 4000–400 cm-1 using KBr pellets. 1H NMR spectra
were recorded on a Bruker AVANCE-400 MHZ spectrometer
with chloroform (CDCl3) as the solvent. Chemical shift values
are reported in ppm (d) relative to tetramethysilane as the
internal standard. Analytical thin-layer chromatography was
carried out on precoated plates (silica gel 60 F254), and spots
were visualized with UV light.
General procedure for the synthesis of the compounds 2a–
2h, 3a–3d. A mixture of nitenpyram (2.71 g, 10 mmol), amino
acid benzyl ester hydrochloride or amino acid tetrahydrofurfur-2-yl
ester hydrochloride (12 mmol), Et3N (1.7 mL), and formaldehyde
(1.95 mL, 37%) in ethanol (20mL) was heated to 65oC for 5 min
Figure 2. Development of novel nitenpyram analogs in our previous study. [Color figure can be viewed in the online issue, which is available at
wileyonlinelibrary.com.]
Journal of Heterocyclic Chemistry
DOI DOI 10.1002/jhet

Month 2013
Two Series of Novel (Z)-nitenpyam Analogs
Scheme 1. General synthetic route for the target compounds (2a–2h, 3a–3d). Reagents and conditions: (a) SOCl2, benzyl alcohol or tetrahydrofurfur-2-yl
alcohol, various amino acid, stirred at a temperature of 80ꢀC (80–85%); and (b) amino acid benzyl ester hydrochloride or tetrahydrofurfur-2-yl ester hydro-
chloride, HCHO, Et3N/EtOH,65ꢀC, refluxing (66–76%). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
in a microwave reactor and stirred for 20min at the temperature.
Then, cooled to room temperature, the reaction mixture was
concentrated under reduced pressure and treated with 20mL of
water. Then, the solution was extracted three times with ethyl
acetate, and the combined extracts were dried over MgSO4. The
organic phase was evaporated under reduced pressure, and crude
product was subjected to flash chromatography on silica gel,
eluting with ethyl acetate/petroleum ether to afford pure products.
(CH3)2). IR (KBr, cm-1) n: 2938, 2880, 1731, 1557, 1249. MS
(ESI): [M+ H]+502.2; Anal. Calcd for C25H32ClN5O4: C, 59.81;
H, 6.43; N, 13.95; Found:C, 59.75; H, 6.48; N, 13.92. [a]
25 = +10.781 (C= 0.01g/mL CH3COCH3).
D
Z-(+)-2-[4-[N-(6-chloro-3-pyridyl)methyl-N-ethyl]amino-3-
methyl-5-nitro-1,2,3,6-tetrahydropyrimidin-1-yl]-4- sulfidomethyl
benzyl butanate (2c).
Yield 66%; yellow oil; 1H NMR
(CDCl3, 400 MHz) d 8.30 (dd, J = 15.5, 2.2 Hz, 1H, Pyridine),
7.75–7.63 (m, 1H, Pyridine), 7.38 (dd, J = 3.7, 1.7Hz, 1H,
Pyridine), 7.37–7.30 (m, 5H, PhH), 5.19–5.08 (m, 2H, O-CH2-
Ph), 4.51 (t, J = 14.8Hz, 1H, Py-CH2), 4.15 (dd, J = 10.9, 3.7 Hz,
1H, Py-CH2), 3.77–3.72 (m, 4H), 3.69 (d, J= 6.0 Hz, 3H, SCH3),
3.67–3.63 (m, 1H, NCHCO), 3.25–3.19 (m, 1H), 2.97–2.84 (m,
1H), 2.82 (d, J= 2.9 Hz, 3H, NCH3), 2.50 (dt, J= 17.2, 7.5 Hz, 2H,
CH2SCH3), 2.04–1.95 (m, 2H, CHCH2), 1.17 (t, J=7.1, 3H,
NCH2CH3). IR (KBr, cm-1) n: 2923, 2860, 1731, 1555, 1251. MS
(ESI): [M + H]+534.2; Anal. Calcd for C25H32ClN5O4S: C, 56.22;
H, 6.04; N, 13.11; Found:C,56.28; H,5.98; N,13.16. [a]
The analytical data for the compounds 2a–2h, 3a–3d were
summarized as follows:
Z-(+)-2-[4-[N-(6-chloro-3-pyridyl)methyl-N-ethyl]amino-3-
methyl-5-nitro-1,2,3,6-tetrahydropyrimidin-1-yl] benzyl propanate
1
(2a). Yield 70%; yellow oil; H NMR (d, CDCl3, 400 MHz) d
8.30 (s, 1H, Pyridine), 7.79–7.59 (m, 1H, Pyridine), 7.37 (d,
J = 9.1 Hz, 1H, Pyridine), 7.36–7.27 (m, 5H, Ph-H), 5.15 (q,
J = 12.1Hz, 2H, O-CH2-Ph), 4.51 (dd, J = 15.0, 5.1 Hz, 1H, Py-
CH2), 4.19–4.11 (dd, 1H, Py-CH2), 3.85–3.66 (m, 4H), 3.62 (dd,
J = 14.3, 7.1 Hz, 1H, NCHCO), 3.24–3.10 (m, 1H), 2.83–2.90 (m,
1H), 2.89 (s, 3H, NCH3), 1.41 (d, J = 7.0Hz, 3H, CHCH3), 1.15
(dd, J = 15.5, 7.2 Hz, 3H, NCH2CH3). IR (KBr, cm-1) n: 2932,
2878, 1733, 1551, 1260. MS (ESI): [M+ H]+474.1; Anal. Calcd
for C23H28ClN5O4: C, 58.29; H, 5.95; N, 14.78; Found:C,58.35;
H,5.89; N,14.82. [a]D25 = +21.836 (C = 0.01g/mL CH3COCH3).
Z-(+)-2-[4-[N-(6-chloro-3-pyridyl)methyl-N-ethyl]amino-3-
methyl-5-nitro-1,2,3,6-tetrahydropyrimidin-1-yl]-3-methyl benzyl
25 = +16.567 (C = 0.01 g/mL CH3COCH3).
D
Z-(+)-2-[4-[N-(6-chloro-3-pyridyl)methyl-N-ethyl]amino-3-
methyl-5-nitro-1,2,3,6-tetrahydropyrimidin-1-yl]-3-methyl benzyl
pentanate(2d).
Yield 68%; yellow oil; 1H NMR (CDCl3,
400 MHz) d 8.30 (dd, J = 9.9, 2.1 Hz, 1H,Pyridine), 7.70–7.61 (m,
1H,Pyridine), 7.44(d, J= 9.0 Hz, 1H, Pyridine),7.46–7.28 (m, 5H,
Ph-H), 5.20–5.07 (m, 2H, O-CH2-Ph), 4.51 (dd, J= 15.0, 4.3 Hz,
1H, Py-CH2), 4.23–4.12 (m, 1H,Py-CH2), 3.86–3.65 (m, 4H), 3.59
(t, J= 7.4 Hz, 1H,NCHCO), 3.26–3.20 (m, 1 H), 2.98–2.89 (m,
1H), 2.87 (t, J = 7.5 Hz, 3H, NCH3), 1.73–1.64 (m, 1H, CHCH3),
1.62 (d, J= 13.1 Hz, 2H, CH2CH3), 1.17 (q, J=7.0Hz, 3H,
NCH2CH3), 1.00–0.93 (m, 3H, CHCH3), 0.90 (t, J=7.3Hz, 3H,
CH2CH3). IR(KBr, cm-1) n: 2933, 2871, 1732, 1553, 1250. MS
(ESI): [M + H]+516.3; Anal. Calcd for C26H34ClN5O4: C, 60.52; H,
6.64; N, 13.57; Found:C,60.57; H,6.57; N,13.53. [a]2D5 = +31.740
(C = 0.01 g/mL CH3COCH3).
butanate (2b).
Yield 68%; yellow oil; 1H NMR (CDCl3,
400 MHz) d 8.30 (dd, J = 11.1, 2.1 Hz, 1H, Pyridine), 7.69–7.58
(m, 1H, Pyridine), 7.46(d, J= 9.3 Hz, 1H, Pyridine),7.48–7.29 (m,
5H, Ph-H), 5.21–5.08 (m, 2H, O-CH2-Ph), 4.51 (dd, J= 15.0,
5.2 Hz, 1H, Py-CH2), 4.25–4.13 (m, 1H, Py-CH2), 3.74–3.68 (m,
4H), 3.26 (m, 1H), 3.09 (dd, J = 10.2, 2.7 Hz, 1H, NCHCO), 2.93
(d, J = 5.3Hz, 3H, NCH3), 2.91–2.85 (m, 1H), 2.09–1.98 (m, 1H,
CH(CH3)2), 1.17 (dd, J = 16.0, 7.2 Hz, 3H, NCH2CH3), 1.05 (dd,
J = 10.0, 6.6 Hz, 3H, CH(CH3)2), 0.89 (d, J = 6.6 Hz, 3H, CH
Journal of Heterocyclic Chemistry
DOI DOI 10.1002/jhet

C.-W. Sun, T. Fang, Z.-B. Hao, C.-C. Pang, X. Xu, and H.-J. Xin
Vol 000
Table 1
Insecticidal activities of the target compounds (2a–2h), (3a–3d) against Nilaparvata lugens.
Mortality (%) at different concentration (mg/L)
500 100 20
100 90
Compound
n
R1
R2
2a
0
CH3
34
40
46
60
38
45
55
68
72
90
76
92
100
2b
0
0
0
0
0
0
0
0
1
0
1
(CH3)2CH
100
100
100
100
100
100
100
100
100
100
100
100
92
95
2c
CH3SCH2CH2
2d
CH3CH2CH(CH3)
96
2e
CH3
92
2f
(CH3)2CH
95
2g
CH3SCH2CH2
96
2h
CH3CH2CH(CH3)
100
95
3a
H
H
H
H
3b
100
100
100
100
3c
3d
Nitenpyram
Z-(+)-2-[4-[N-(6-chloro-3-pyridyl)methyl-N-ethyl]amino-3-
methyl-5-nitro-1,2,3,6-tetrahydropyrimidin-1-yl] tetrahydrofurfur-
2-yl propanate (2e). Yield 72%; brown oil; H NMR (CDCl3,
(dt, J= 7.0, 3.5 Hz, 3H, CHCH3), 1.18 (dt, J= 14.5, 7.1 Hz, 3H,
NCH2CH3). IR (KBr, cm-1) n: 2942, 2865, 1730, 1550, 1247. MS
(ESI): [M + H]+468.1; Anal. Calcd for C21H30ClN5O5 :C, 53.90; H,
6.46; N, 14.97; Found: C, 53.83; H, 6.42; N, 15.01; [a]2D5 = +21.831
(C = 0.01 g/mL CH3COCH3).
Z-(+)-2-[4-[N-(6-chloro-3-pyridyl)methyl-N-ethyl]amino-
3-methyl-5-nitro-1,2,3,6-tetrahydropyrimidin-1-yl]-3-methyl
tetrahydrofurfur-2-yl butanate (2f). Yield 69%; yellow oil; 1H
NMR (CDCl3, 400 MHz) d 8.30 (dd, J = 10.4, 2.6 Hz, 1H,
Pyridine), 7.69–6.58 (m, 1H, Pyridine), 7.46(d, J = 9.6 Hz, 1H,
Pyridine), 4.51 (dd, J = 13.9, 6.7 Hz, 1H,Py-CH2), 4.33–4.21
1
400 MHz) d 8.33 (s, 1H, Pyridine), 7.74 (dd, J= 8.1, 2.2 Hz, 1H,
Pyridine), 7.34 (d, J= 8.2 Hz, 1H, Pyridine), 4.55 (dd, J= 15.0,
5.5 Hz, 1H, Py-CH2), 4.22 (dd, J= 10.9, 3.1 Hz, 1H, Py-CH2), 4.13
(dt, J= 11.3, 6.2 Hz, 2H, O-CH2-THF), 3.88 (dd, J= 14.4, 7.3 Hz,
1H, THF-H), 3.79–3.73 (m, 4H), 3.74–3.61 (m, 2H, THF-H), 3.27–
3.20 (m, 1H), 3.00–2.95 (d, J=6.8, 3H, NCH3), 2.92 (d, J=5.8Hz,
1H), 2.88 (d, J= 4.9 Hz, 1H, NCHCO), 2.05–1.98 (m, 1H, THF-H),
1.98–1.85 (m, 2H, THF-H), 1.67–1.54 (m, 1H, THF-H), 1.44
Journal of Heterocyclic Chemistry
DOI DOI 10.1002/jhet

Month 2013
Two Series of Novel (Z)-nitenpyam Analogs
(m, 1H, Py-CH2), 4.12–3.91 (m, 2H, O-CH2-THF), 3.85
(dd, J = 15.1, 7.0 Hz, 1H, THF-H), 3.74–3.68 (m, 4H), 3.65–3.58
(m, 2H, THF-H), 3.26–3,12 (m, 1H), 3.05 (dd, J = 10.6, 3.7 Hz,
1H, NCHCO), 2.95 (d, J = 5.9 Hz, 3H, NCH3), 2.91–2.79 (m, 1H),
2.12–2.03 (m, 1H, CH(CH3)2), 2.07–2.01 (m, 1H, THF-H), 1.98–
1.85 (m, 2H, THF-H), 1.67–1.54 (m, 1H, THF-H), 1.17
(dd, J= 15.4, 8.2 Hz, 3H, NCH2CH3), 1.05 (dd, J= 11.5, 7.6 Hz,
3H, CH(CH3)2), 0. 93 (d, J= 6.9 Hz, 3H, CH(CH3)2). IR(KBr,
cm-1) n: 2935, 2872, 1730, 1549, 1251. MS (ESI):[M + H]+
496.4; Anal. Calcd for C23H34ClN5O5: C, 55.69; H, 6.91; N,
14.12; Found: C, 55.75; H, 6.89; N, 14.18[a]2D5 =+10.775
(C = 0.01 g/mL CH3COCH3).
Z-(+)-2-[4-[N-(6-chloro-3-pyridyl)methyl-N-ethyl]amino-3-
methyl-5-nitro-1,2,3,6-tetrahydropyrimidin-1-yl]-4- sulfidomethyl
tetrahydrofurfur-2-yl butanate (2g). Yield 66%; yellow oil; 1H
NMR (CDCl3, 400 MHz) d 8.30 (dd, J = 13.5, 2.9 Hz, 1H,
Pyridine), 7.85–7.73 (m, 1H, Pyridine), 7.38 (dd, J= 4.7, 2.3Hz,
1H, Pyridine), 4.56 (dd, J = 14.9, 5.7 Hz, 1H, Py-CH2), 4.31–4.23
(m, 1H, Py-CH2), 4.15–3.90 (m, 2H, O-CH2-THF), 3.82 (dd,
J = 15.1, 7.0 Hz, 1H, THF-H), 3.78–3.70 (m, 4H), 3.68 (d,
J =6.0 Hz, 3H, SCH3), 3.65–3.58 (m, 2H, THF-H), 3.55–3.49 (m,
1H, NCHCO), 3.25–3.14 (m, 1H), 2.98–2.82 (m, 1H), 2.80 (d,
J = 2.9 Hz, 3H, NCH3), 2.48 (dt, J= 17.6, 8.1 Hz, 2H, CH2SCH3),
2.06–1.96(m, 2H, CHCH2), 1.85–1.80 (m, 1H, THF-H), 1.78–1.68
(dd, J= 19.6, 10.0 Hz, 2H, THF-H), 1.61–1.52 (m, 1H, THF-H),
1.17 (td, J= 7.6, 5.1 Hz, 3H, NCH2CH3). IR (KBr, cm-1) n: 2941,
2870, 1734, 1545, 1253. MS (ESI):[M + H]+ 528.3; Anal. Calcd
for C23H34ClN5O5S: C, 52.31; H, 6.49; N, 13.26; Found: C,
52.36; H, 6.42; N, 13.29. [a]2D5 = +16.573 (C = 0.01 g/mL
CH3COCH3).
Z-3-[4-[N-(6-chloro-3-pyridyl)methyl-N-ethyl]amino-3-methyl-5-
nitro-1,2,3,6-tetrahydropyrimidin-1-yl] benzyl propanate (3b).
Yield 73%; yellow oil;1H NMR (CDCl3, 400 MHz) d8.30
(d,J = 2.2 Hz, 1H, Pyridine), 7.69 (dd,J = 8.2,2.5Hz, 1H,
Pyridine),7.37 (d,J = 1.4 Hz,1H, Pyridine), 7.36–7.29 (m, 5H, Ph-
H), 5.15(s, 2H, O-CH2-Ph), 4.50 (d, J = 15.0Hz, 1H, Py-CH2),
4.15 (d, J = 15.0 Hz, 1H, Py-CH2), 3.68–3.57(m, 4H), 3.24(dd,
J = 14.1, 7.1 Hz, 1H), 2.97–2.91(m,1H), 2.90 (s, 3H, NCH3), 2.84
(dt, J = 9.3,6.8Hz, 2H, NCH2), 2.61 (t, J = 6.8 Hz, 2H, CH2CO),
1.17 (t, J = 7.1 Hz, 3H, NCH2CH3). IR (KBr, cm-1) n: 2929, 2849,
1733, 1550, 1247. MS (ESI):[M + H]+474.4; Anal. Calcd for
C23H28ClN5O4: C, 58.29; H, 5.95; N, 14.78; Found: C, 58.33; H,
5.89; N, 14.72.
Z-2-[4-[N-(6-chloro-3-pyridyl)methyl-N-ethyl]amino-3-methyl-5-
nitro-1,2,3,6-tetrahydropyrimidin-1-yl] tetrahydrofurfur-2-yl acetate
(3c). Yield 71%; brown oil;1H NMR (CDCl3, 400 MHz) d 8.32 (d,
J= 2.3 Hz, 1H, Pyridine), 7.72 (dd, J= 8.2, 2.4 Hz, 1H, Pyridine), 7.33
(d, J= 8.2 Hz, 1H, Pyridine), 4.53 (d, J= 15.0 Hz, 1H, Py-CH2), 4.23
(dd, J= 10.9, 2.7 Hz, 1H, Py-CH2), 4.17–4.10 (m, 2H, O-CH2-
THF),4.10–4.04 (m, 1H, THF-H), 3.93–3.85 (m, 1H, THF-H), 3.82
(d, J= 6.8 Hz, 1H, THF-H), 3.77 (dd, J= 14.4, 5.9 Hz, 4H), 3.49
(s, 2H, NCH2CO), 3.26 (dd, J= 14.0, 7.1 Hz, 1H), 3.05 (s, 3H,
NCH3), 2.92 (dd, J = 14.1, 7.1 Hz, 1H), 2.04–1.98 (m, 1H, THF-
H), 1.98–1.86 (m, 2H, THF-H), 1.60–1.51 (m, 7.3Hz, 1H, THF-
H), 1.17 (t, J = 7.1 Hz, 3H, NCH2CH3). IR (KBr, cm-1) n: 2933,
2871, 1744, 1549, 1250. MS (ESI):[M + H]+ 460.1; Anal. Calcd
for C20H28ClN5O5: C, 52.92; H, 6.22; N, 15.43; Found: C, 52.98;
H, 6.25; N, 15.37.
Z-3-[4-[N-(6-chloro-3-pyridyl)methyl-N-ethyl]amino-3-methyl-
5-nitro-1,2,3,6-tetrahydropyrimidin-1-yl] tetrahydrofurfur-2-yl
propanate (3d).
Yield 74%; brown oil; 1H NMR (CDCl3,
Z-(+)-2-[4-[N-(6-chloro-3-pyridyl)methyl-N-ethyl]amino-3-
methyl-5-nitro-1,2,3,6-tetrahydropyrimidin-1-yl]-3-methyl
400 MHz) d 8.34–8.25 (m, 1H, Pyridine), 7.69 (dd, J = 8.2,
2.5 Hz, 1H, Pyridine), 7.31 (d, J = 8.2Hz, 1H, Pyridine), 4.50 (d,
J = 15.0 Hz, 1H, Py-CH2), 4.19 (dd, J = 8.4, 2.6 Hz, 1H, Py-CH2),
4.11–4,05 (m, 2H, O-CH2-THF), 4.02 (dd, J = 11.1, 6.8Hz, 1H,
THF-H), 3.87 (dt, J = 8.3, 6.7 Hz, 1H, THF-H), 3.78 (dt, J = 7.2,
6.7 Hz, 1H, THF-H), 3.68–3.58 (m, 4H), 3.24 (dd, J = 14.1,
7.1 Hz, 1H), 2.97 (d, J = 4.0 Hz, 3H, NCH3), 2.92 (dd, J = 14.1,
7.2 Hz, 1H), 2.82 (dt, J = 9.5, 6.8 Hz, 2H, NCH2), 2.59 (t,
J = 6.8Hz, 2H, CH2CO), 2.02–1.96 (m, 1H, THF-H), 1.91–1.83
(m, 2H, THF-H), 1.67–1.52 (m, 1H, THF-H), 1.17 (t, J = 7.2 Hz,
3H, NCH2CH3). IR (KBr, cm-1) n: 2933, 2870, 1733, 1550, 1248.
MS (ESI):[M+ H]+ 472.2; Anal. Calcd for C21H30ClN5O5 C,
53.90; H, 6.46; N, 14.97; Found: C, 53.97; H, 6.42; N, 14.95.
tetrahydrofurfur-2-yl pentanate (2h).
Yield 68%; brown
oil;1H NMR (CDCl3, 400MHz) d 8.31 (d, J = 11.2 Hz, 1H,
Pyridine), 7.70 (dd, J = 9.0, 8.0 Hz, 1H, Pyridine), 7.33
(d, J = 8.2 Hz, 1H, Pyridine), 4.52 (dd, J = 14.9, 5.7 Hz, 1H,
Py-CH2), 4.28–4.18 (m, 1H, Py-CH2), 4.13–3.98 (m, 2H,
O-CH2-THF), 3.88 (dd, J = 15.1, 7.0 Hz, 1H, THF-H), 3.84–
3.70 (m, 4H), 3.69–3.55 (m, 2H, THF-H), 3.29 (dd, J = 13.7,
6.9 Hz, 1H), 3.22 (d, J = 10.1 Hz, 1H, NCHCO), 2.99 (d,
J = 10.9, 3H, NCH3), 2.90 (d, J = 7.2 Hz, 1H), 2.01 (dd,
J = 12.3, 6.9 Hz, 1H, CHCH3), 1.97–1.85 (m, 3H, CHCH3),
1.75 (m, 1H, THF-H), 1.65 (dd, J = 19.6, 10.0 Hz, 2H, THF-H),
1.61–1.52 (m, 1H, THF-H), 1.19 (dd, J = 13.9, 7.0 Hz, 3H,
NCH2CH3), 0.97–0.87 (m, 5H, CH2CH3). IR (KBr, cm-1) n:
2936, 2865, 1731, 1547, 1248. MS (ESI):[M + H]+510.2; Anal.
Calcd for C24H36ClN5O5: C, 56.52; H, 7.11; N, 13.73; Found:
C, 56.59; H, 7.10; N, 13.79.[a]2D5 = +31.745 (C = 0.01 g/mL
CH3COCH3).
Acknowledgments. This work was supported by the National
Natural Science Foundation of China (21042010 and 30870560),
the Key Scientific and Technological Project of Shanghai Science
and Technology Commission (09391912100), the Leading
Academic Discipline Project of Shanghai Normal University
(DZL808), and the Innovation Project of Shanghai Education
Commission (09YZ157). We are also grateful for the support
from the Branch of National Pesticide R&D South Center.
Z-2-[4-[N-(6-chloro-3-pyridyl)methyl-N-ethyl]amino-3-methyl-5-
nitro-1,2,3,6-tetrahydropyrimidin-1-yl] benzyl acetate (3a). Yield
68%; yellow oil;1H NMR (CDCl3, 400 MHz) d 8.31 (s, 1H,
Pyridine), 7.71 (d, J = 8.0 Hz, 1H, Pyridine),7.52 (d,
J = 9.1 Hz, 1H, Pyridine), 7.50–7.15 (m, 5H, Ph-H), 5.26 (s,
2H, O-CH2-Ph), 4.52 (d, J = 14.8 Hz, 1H, Py-CH2), 4.22–
4.11 (m, 1H, Py-CH2), 3.71–3.63 (m, 4H), 3.46 (d,
J = 10.0 Hz, 2H, NCH2CO), 3.25–2.95 (m, 1H), 2.98 (d,
J = 9.9 Hz, 3H, NCH3), 2.92–2.85 (m, 1H), 1.17 (t,
J = 6.9 Hz, 3H, NCH2CH3). IR (KBr, cm-1) n:2919, 2850,
1744, 1542, 1248. MS (ESI):[M + H]+ 460.1; Anal. Calcd for
C23H28ClN5O4: C, 58.29; H, 5.95; N, 14.78; Found: C,
58.24; H, 5.90; N, 14.71.
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