Synthesis, insecticidal and fungicidal activities of methyl 2-(methoxyimino)-2-(2-((1-(N′-nitrocarbamimidoyl)-2-hydrocarbylidene-hydrazinyl)methyl)phenyl)acetates

Article abstract of DOI:10.1039/c5ra27359e

N′-Nitro-2-hydrocarbylidenehydrazinecarboximidamides and methoxyacrylates are two types of important agrochemicals. By combining their key fragments into one framework, a series of the title compounds was designed and synthesized. Some of these compounds have shown excellent insecticidal activities for aphides, for example, the LC₅₀ values of compounds 6-06, 6-11 and 6-19 against M. perslcae and H. amygdale were found to be 1.9/14.4, 13.4/1.5 and 0.3/38.4 mg L^-1 respectively. They were also effective against the mycelium growth of B. cinerea in vitro. Compound 6-04 could control (～100%) cucumber anthrax and rice blast at 100 mg L^-1 in vivo, and inhibit the spore germination (～100%) of vegetable gray mold at 6.25 mg L^-1. These compounds could be considered as potential insecticidal or fungicidal candidates for crop protection. The results of structure-activity relationship (SAR) studies are discussed.

Full text of DOI:10.1039/c5ra27359e

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COMMUNICATION
Synthesis, insecticidal and fungicidal activities of
methyl 2-(methoxyimino)-2-(2-((1-(N0-
nitrocarbamimidoyl)-2-hydrocarbylidene-
hydrazinyl)methyl)phenyl)acetates†
Cite this: RSC Adv., 2016, 6, 19916
Received 21st December 2015
Accepted 4th February 2016
Xiaoyong Yuan,‡ab Changqing Jia,‡a Yongqiang Ma,a Dongyan Yang,a Changhui Ruic
DOI: 10.1039/c5ra27359e
a
*
and Zhaohai Qin
www.rsc.org/advances
N0-Nitro-2-hydrocarbylidenehydrazinecarboximidamides
and produce novel bioactive molecules, such as insecticides,
methoxyacrylates are two types of important agrochemicals. By herbicides and fungicides.7 For example, uacrypyrim (1),8
combining their key fragments into one framework, a series of the title which was developed by Nippon Soda Co., was the rst acaricide
compounds was designed and synthesized. Some of these bearing a methoxyacrylate moiety and also works on respiratory
compounds have shown excellent insecticidal activities for aphides, chain cyt bc1. HPNC-A3066 (2) (ref. 9) exhibited a good efficacy
for example, the LC50 values of compounds 6-06, 6-11 and 6-19 of control against two-spotted spider mites, the European red
against M. perslcae and H. amygdale were found to be 1.9/14.4, 13.4/ mite (Panonychus ulmi) and citrus red mite (Panonychus citri).
1.5 and 0.3/38.4 mg Lꢀ1 respectively. They were also effective against Whereas compound 3 was developed as a herbicide.10
the mycelium growth of B. cinerea in vitro. Compound 6-04 could
control (ꢁ100%) cucumber anthrax and rice blast at 100 mg Lꢀ1 in vivo,
and inhibit the spore germination (ꢁ100%) of vegetable gray mold at
6.25 mg Lꢀ1. These compounds could be considered as potential
insecticidal or fungicidal candidates for crop protection. The results of
structure–activity relationship (SAR) studies are discussed.
Guadipyr (4) is a novel insecticide developed in our labora-
tory that has a high efficiency for controlling aphis, rice plan-
thoppers and leaf hoppers, and a low toxicity to honeybees
and earthworms.11,12 The crucial moiety, N0-nitrohydrazine-
1 Introduction
carboximidamide, along with its structural analogs semi-
carbazones and thiosemicarbazones, is a core structure of many
Methoxyacrylate fungicides, some of the most potent and
other bioactive molecules.13–19 For this study, we considered
successful agrochemicals in recent decades,1 originate from the
combining (2-(2-methoxyimino)methoxycarbonyl methyl)benzyl,
a very common toxophore in fungicides, such as in tri-
oxystrobin (5), with N0-nitrohydrazinecarboximidamides, so
natural product strobilurin A and have low toxicity, high effi-
ciency and a broad spectrum of activity. Recently, many exam-
ples have proven that modication of the side chain of
that a new class of bioactive compounds (6) could be created and
strobilurin fungicides is the most effective way to obtain new
investigated for agricultural application (Fig. 1).
analogues with a higher activity.2a–i Based on biological activity
similarities3,4 and the principle of combination of active sub-
structures,5,6 a great many efforts have focused on the linkage of
toxophore methoxyacrylate and other bioactive blocks to
aCollege of Science, China Agricultural University, Beijing 100193, China. E-mail:
qinzhaohai@263.net; Fax: +86-10-62732958.; Tel: +86-10-62732958
bNational Navel Orange Engineering Research Center, Gannan Normal University,
Ganzhou 341000, Jiangxi Province, China
cInstitute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing
100193, China
† Electronic supplementary information (ESI) available: The synthetic procedures
and NMR spectra of the intermediates, and the NMR and HRMS spectra of the title
compounds are freely available. See DOI: 10.1039/c5ra27359e
‡ These authors contributed equally to the article.
Fig. 1 Design of the title compounds.
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2 Results and discussion
Synthesis
A similar strategy as for guadipyr preparation11 was used to
produce 6, in which 2-nitroguanidine 7 was hydrazinolated to
give 8, and the later was condensed with aldehydes or ketones to
produce the key intermediate 9. A direct nucleophilic substi-
tution reaction between (E)-methyl 2-(2-(bromomethyl)phenyl)-
2-(methoxyimino) acetate and 9 in the presence of a base gave
the title compound 6 with low to moderate yields (Scheme 1).
The hybrid compounds (6) exhibited both excellent insecticidal
and fungicidal activities. In this paper we present the synthesis
and bioactivities of the title compounds in detail. Their struc-
ture–activity relationships and some problems with the
synthesis are also discussed.
The synthetic yields of the target compounds were only
between 14% and 47%, the reason being that compound 6 was
also reactive under the condensation conditions used in the last
step (Scheme 1), resulting in several byproducts. Firstly,
compound 6 could be further alkylated to give the double
substituted compound 10. Secondly, when the carbonyl
compound (RR1C]O) was an aldehyde, compound 6 could be
transformed into compound 11 via a complicated ring-closure/
dehydrogenation process. When the carbonyl compound
(RR1C]O) was a ketone, although 11 could no longer be formed
because of the absence of the hydrogen, another interesting
denitroamine reaction took place and byproduct 12 was ob-
tained (Scheme 2). Although these side reactions were unfa-
vorable for the title compound preparation, the byproducts 11
and 12 were also attractive. Related research is being carried out
in our laboratory.
Scheme 2 Side reactions during the condensation.
activity against the two kinds of aphids. Notably, compounds 6-
06 and 6-19 exhibited exceptional insecticidal activities with
a LC50 of 1.9 and 0.3 mg mLꢀ1 against M. perslcae, respectively.
For the aliphatic series (compounds 6-01 to 6-06), when R1 or R2
was a bulky alkyl bearing side chain, the activity decreased
sharply (compounds 6-02 and 6-03). For the aromatic series, an
ortho-substituent, no matter if it was electron-withdrawing or
electron-donating, was the most important factor in enhancing
the activity. For example, compounds 6-11 and 6-19 exhibited
excellent activity in both assays. But this observation was not
true for compound 6-23, an ortho-hydroxyl substituted analog
which had a much weaker activity, especially with M. perslcae
(Sulzer). The reason might be that it could form unnecessary
hydrogen bonds at the active site. When the hydroxyl group was
moved to the meta position (compound 6-22), the activity was
enhanced remarkably. The presence of a para-substituent was
another key factor affecting the activities. A weak electron-
donating or -withdrawing substituent at this position, such as
a chlorine atom (6-10, 6-12) or alkyl group (6-15, 6-16) was
benecial. But a strong substituent, such as a cyano (6-09), nitro
(6-13), or alkyloxy (6-17, 6-20) group signicantly reduced the
activity. These observations were used to clearly sketch out the
outlines of a structure–activity relationship model for this series
of compounds and to identify the direction for optimization.
Structure–activity relationship (SAR) studies
Insecticidal activity. The insecticidal activities of the title
compounds were evaluated using Myzus perslcae (Sulzer) and
Hyalopterus amygdale Blananchard as the target pests and the
results are summarized in Table 1. In general, all of the
compounds displayed considerable to excellent insecticidal
Scheme 1 Preparation of the title compounds.
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Table 1 Insecticidal activity (LC50(95% confidence limit, mg mLꢀ1)) of 6 against M. perslcae (Sulzer) and H. amygdale (Blanchard)
Compd.
MPa
HAb
Compd.
MPa
HAb
Imidacloprid
6-01
6-02
6-03
6-04
6-05
6-06
6-07
6-08
0.2(0.1–0.4)
1.3(0.7–2.3)
5.2(1.5–9.7)
6-12
6-13
6-14
6-15
6-16
6-17
6-18
6-19
6-20
6-21
6-22
6-23
14.9(0.7–31.8)
31.8(25.2–40.0)
4.9(0.1–14.3)
15.3(6.8–23.9)
110.8(53.3–230.0)
56.7(35.8–89.6)
64.7(48.6–86.0)
0.3(0.1–0.7)
87.4(68.1–119.1)
136.8(113.5–172.0)
34.3(18.2–53.9)
24.4(11.2–43.1)
7.3(2.4–12.8)
153.1(79.5–259.0)
111.1(54.5–214.6)
159.5(75.2–338.3)
11.2(4.0–18.5)
25.0(2.9–53.6)
1.9(0.1–9.0)
39.5(27.6–54.5)
32.2(18.8–55.2)
63.3(41.5–107.5)
145.8(76.8–276.6)
13.4(4.7–37.7)
30.4(20.3–41.1)
97.7(58.0–289.0)
81.7(33.5–124.3)
110.4(50.9–301.4)
14.4(5.1–24.2)
12.0(8.0–16.0)
13.7(1.7–27.0)
122.3(67.4–351.2)
3.0(0.1–8.6)
>200
48.7(27.4–105.4)
38.4(27.1–52.6)
45.6(12.5–108.3)
118.3(72.3–305.4)
46.9(30.1–67.5)
26.8(9.1–72.3)
>200
198.7(125.6–341.0)
8.9(3.0–15.4)
6-09
6-10
6-11
1.5(0.003–6.0)
185.6(64.5–333.2)
a
M. perslcae (Sulzer). b H. amygdale Blanchard.
spectrum as azoxystrobin against these phytopathogens, sug-
gesting that they might have a different mode of action to other
strobilurin fungicides. We also didn’t nd an explicit relation-
ship between their structures and fungicidal activities for B.
cinerea mycelium inhibition.
All of the compounds (6) gave poor control in vivo except for
6-04. This compound exhibited 100% control of cucumber
anthrax and rice blast at 100 mg mLꢀ1, and also 100% inhibition
of the spore germination of vegetable gray mold at 6.25 mg mLꢀ1
(Table 3). This revealed that it was both protective and curative,
and that it might be suitable to be developed as a new potential
agricultural fungicide.
Fungicidal activity. The fungicidal activity was investigated
both in vitro and in vivo, and the results are summarized in
Tables 2 and 3 respectively. No obvious differences in the
antifungal activity between the aliphatic and aromatic series
were observed. In general, these compounds were highly active
against Botrytis cinerea and Physalospora piricola Nose in vitro at
50 mg mLꢀ1. Several compounds displayed a higher activity than
azoxystrobin, for example, most of the compounds (6) against B.
cinerea and compounds 6-10 and 6-13 against P. piricola Nose.
Unfortunately, they didn’t display as broad a fungicidal
Table 2 In vitro fungicidal activity of 6 against the phytopathogensa
Mycelium growth inhibitory rate (%) at 50 mg mLꢀ1
3 Experimental
Instruments and materials
Compd.
MS
PC
PI
PP
CO
PA
BC
1H NMR and 13C NMR spectra were obtained at 300 MHz using
a Bruker Avance DPX300 spectrometer in CDCl3 or DMSO-d6
solution with TMS as the internal standard. Chemical shi
values (d) are given in parts per million. HRMS data were ob-
tained using a Thermo Scientic LTQ Orbitrap Discovery (Bre-
men, Germany) instrument. The melting points were
determined on a Cole-Parmer microscope melting point appa-
ratus and are uncorrected. N0-Nitrohydrazinecarboximidamide
(8) and the intermediates (9) were synthesized in our laboratory
and the data are given in the ESI.† All the yields were not
optimized.
Azoxystrobin
6-01
6-02
6-03
6-04
6-05
6-06
6-07
6-08
6-09
6-10
6-11
6-12
6-13
6-14
6-15
6-16
6-17
6-18
6-19
6-20
6-21
6-22
6-23
46.2
4.4
6.1
11.8
13.9
—
10.1
1.3
—
17.4
5.0
—
34.0
—
17.2
25.4
17.0
—
14.5
18.9
—
—
22.5
—
37.0
5.8
6.2
6.5
9.0
3.0
3.7
0.9
8.0
4.3
5.4
6.5
7.5
4.5
6.0
15.3
7.7
4.7
3.2
5.6
4.5
5.6
6.5
3.4
62.2
0.2
20.0
30.5
34.0
7.2
62.5
30.8
35.4
26.1
41.7
30.8
28.3
46.7
51.7
39.2
70.7
44.2
58.3
74.3
31.9
44.4
41.7
19.2
35.0
48.8
33.8
51.7
39.2
33.3
51.1
4.1
17.0
12.7
15.0
4.9
61.3
32.5
35.7
26.1
30.4
18.6
20.2
33.3
27.6
26.4
31.5
19.3
28.3
26.1
23.6
29.8
30.3
23.3
37.6
18.5
20.8
17.5
28.3
21.4
51.1
62.1
34.9
45.2
62.1
58.9
46.8
71.8
60.8
23.7
55.2
64.0
29.0
40.3
66.9
61.3
70.2
53.2
60.9
58.1
53.5
52.4
68.5
36.3
9.8
4.9
5.7
10.0
37.8
24.7
54.1
7.7
22.8
28.4
53.8
36.8
54.3
—
26.6
60.1
13.5
14.7
9.1
14.6
13.8
18.9
14.6
19.1
11.8
15.2
20.3
20.6
5.7
14.2
10.3
8.9
9.7
12.6
6.9
General procedure for the preparation of the title compounds
(6)
A mixture of 9 (26.7 mmol), potassium carbonate (2.67 g, 19.34
mmol), a catalytic quantity of cesium carbonate, and acetoni-
trile (100 mL) was stirred for 1 h. (E)-Methyl 2-(2-(bromomethyl)
phenyl)-2-(methoxyimino)acetate19 (12.83 g, 45.0 mmol) was
added, and the reaction mixture was heated to reux for 2.5 h.
Aer cooling, the solid was ltered off, and the ltrate was
concentrated in vacuo. The residue was puried using silica gel
chromatography with petroleum ether/ethyl acetate (v/v ¼ 1 : 1)
as the eluent to give the title compound 6.
1.4
a
MS ¼ M. Sterillia; PC ¼ P. capsici; PI ¼ P. infestans (Mont.) De Bary;
PP ¼ P. piricola Nose; CO ¼ C. orbiculare (Berk. & Ment.); PA ¼ P.
aphanidermatum (Edson) Fitzpatrick; BC ¼ B. cinerea.
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Table 3 In vivo fungicidal activity of 6-04 against the phytopathogens
Inhibitory rate (%) at 100 mg mLꢀ1
Spore germination inhibitory
rate (%) at 6.25 mg mLꢀ1
Vegetable gray
Compd.
Cucumber anthrax
Rice blast
mold
6-04
100
100
—
100
—
100
—
100
—
—
Prochloraz
Isoprothiolane
SYP-Z048a
—
100
a
Used at 2.8 mg Lꢀ1
.
3H), 4.19 (s, 1H), 4.59 (s, 2H), 7.13–7.46 (m, 4H), 8.22 (s, 1H). 13
C
Data for (E)-methyl 2-(methoxyimino)-2-(2-((2-butylidene-1-
NMR (75 MHz, DMSO-d6) d 25.1, 48.4, 52.7, 63.5, 76.2, 127.6,
128.7, 128.9, 129.5, 129.9, 134.6, 148.8, 157.3, 159.1, 163.0.
HRMS (ESI) m/z calcd for C15H20N6O5 (M + H)+ 365.1568, found
365.1568.
(N-nitrocarbamimidoyl)hydrazinyl)methyl)phenyl)acetate
(6-
1
ꢂ
01). Yield 21%; yellowish solid; mp 160–162 C; H NMR (300
MHz, DMSO-d6) d 0.75 (t, J ¼ 7.4 Hz, 3H), 1.46–1.32 (m, 2H),
2.27–2.21 (m, 2H), 3.81 (s, 3H), 4.02 (s, 3H), 4.99 (s, 2H), 7.08–
6.87 (m, 2H), 7.26–7.21 (m, 1H), 7.48–7.33 (m, 2H), 8.57 (s, 1H),
9.03 (s, 1H). 13C NMR (75 MHz, DMSO-d6) d 13.4, 19.5, 34.3,
44.3, 53.0, 63.8, 125.6, 127.5, 128.6, 129.2, 132.7, 148.6, 149.2,
158.3, 162.8. HRMS (ESI) m/z calcd for C16H22N6O5 (M + H)+
379.1724, found 379.1724.
Data
for
(E)-methyl
2-(methoxyimino)-2-(2-((1-(N-
nitrocarbamimidoyl)-2-(pentan-3-ylidene)hydrazinyl)methyl)
phenyl)acetate (6-06). Yield 19%; yellowish solid; mp 130–132
ꢂC; 1H NMR (300 MHz, DMSO-d6) d 0.78 (t, J ¼ 7.35 Hz, 6H), 1.59
(q, J ¼ 7.41 Hz, 4H), 3.75 (s, 3H), 3.96 (s, 3H), 4.34 (s, 2H), 5.32 (s,
1H), 6.99 (d, J ¼ 7.29 Hz, 1H), 7.34–7.46 (m, 3H), 9.39 (s, 1H). 13
C
Data for (E)-methyl 2-(methoxyimino)-2-(2-((2-(2-methyl-
pentylidene)-1-(N-nitrocarbamimidoyl)hydrazinyl)methyl)
phenyl)acetate (6-02). Yield 15%; white solid; mp 103–105 C;
NMR (75 MHz, DMSO-d6) d 7.7, 29.1, 48.6, 52.8, 63.5, 81.4, 127.6,
128.7, 128.8, 129.5, 130.0, 134.4, 148.8, 158.4, 163.0. HRMS (ESI)
m/z calcd for C17H24N6O5 (M + H)+ 393.1881, found 393.1872.
Data for (E)-methyl 2-(2-((2-(furan-2-ylmethylene)-1-(N-nitro-
carbamimidoyl)hydrazinyl) methyl)phenyl)-2-(methoxyimino)
ꢂ
1H NMR (300 MHz, CDCl3) d 0.79 (t, J ¼ 7.2 Hz, 3H), 0.95 (d, J ¼
6.81 Hz, 3H), 0.98–1.30 (m, 4H), 2.28–2.42 (m, 1H), 3.91 (s, 3H),
4.10 (s, 3H), 5.01–5.10 (br s, 2H), 6.90 (d, J ¼ 6.09 Hz, 1H), 6.97–
7.38 (m, 4H), 7.60 (s, 1H), 9.16 (s, 1H). 13C NMR (75 MHz, CDCl3)
d 13.7, 17.2, 19.7, 36.2, 36.9, 44.4, 52.9, 63.8, 125.5, 127.2, 128.5,
128.6, 129.6, 132.0, 148.4, 153.9, 158.7, 163.0. HRMS (ESI) m/z
calcd for C18H26N6O5 (M + H)+ 407.2037, found 407.2034.
Data for (E)-methyl 2-(methoxyimino)-2-(2-((2-(2-ethyl-
butylidene)-1-(N-nitrocarbamimidoyl)hydrazinyl)methyl)
phenyl)acetate (6-03). Yield 26%; yellowish solid; mp 139–141
1
acetate (6-07). Yield 26%; yellowish solid; mp 217–219 ꢂC; H
NMR (300 MHz, DMSO-d6) d 3.81 (s, 3H), 4.04 (s, 3H), 5.12 (s,
2H), 6.62–7.82 (m, 7H), 7.55 (s, 1H), 8.65–9.12 (br s, 2H). 13C
NMR (75 MHz, DMSO-d6) d 44.7, 53.1, 63.8, 112.7, 113.4, 127.7,
129.0, 129.4, 130.1, 132.4, 134.1, 145.7, 148.6, 149.5, 158.2,
162.9. HRMS (ESI) m/z calcd for C17H18N6O6 (M + H)+ 403.1361,
found 403.1360.
1
ꢂC; H NMR (300 MHz, DMSO-d6) d 0.62 (t, J ¼ 7.40 Hz, 6H),
Data for (E)-methyl 2-(methoxyimino)-2-(2-((2-benzylidene-1-
(N-nitrocarbamimidoyl)hydrazinyl)methyl)phenyl)acetate
(6-
1.19–1.41 (m, 4H), 2.07–2.13 (m, 1H), 3.79 (s, 3H), 4.00 (s, 3H),
5.00 (s, 2H), 6.76 (d, J ¼ 7.15 Hz, 1H), 6.92–7.42 (m, 4H), 8.46 (s,
1H), 9.10 (s, 1H). 13C NMR (75 MHz, DMSO-d6) d 11.3, 25.1, 44.1,
45.6, 53.0, 63.8, 125.6, 127.5, 129.0, 129.3, 129.7, 132.6, 148.5,
152.9, 158.3, 162.9. HRMS (ESI) m/z calcd for C18H26N6O5 (M +
H)+ 407.2037, found 407.2031.
1
ꢂ
08). Yield 18%; yellowish solid; mp 214–216 C; H NMR (300
MHz, DMSO-d6) d 3.84 (s, 3H), 4.03 (s, 3H), 5.17 (s, 2H), 7.02–
7.82 (m, 9H), 7.70 (s, 1H), 9.05 (br s, 2H). 13C NMR (75 MHz,
DMSO-d6) d 44.7, 53.1, 63.9, 125.6, 127.6, 128.0, 129.0, 129.3,
130.0, 130.7, 132.8, 133.7, 144.4, 148.6, 158.4, 163.1. HRMS (ESI)
m/z calcd for C19H20N6O5 (M + H)+ 413.1568, found 413.1566.
Data for (E)-methyl 2-(methoxyimino)-2-(2-((2-(4-cyanobenzyli-
dene)-1-(N-nitrocarbamimidoyl)hydrazinyl)methyl)phenyl)acetate
(6-09). Yield 43%; white solid; mp 207–209 ꢂC; 1H NMR (300
MHz, DMSO-d6) d 3.84 (s, 3H), 4.04 (s, 3H), 5.18 (s, 2H), 7.05 (d,
J ¼ 8.33 Hz, 1H), 7.24 (dd, J1 ¼ 1.06 Hz, J2 ¼ 7.13 Hz, 1H), 7.32–
7.42 (m, 2H), 7.70 (s, 1H), 7.88 (d, J ¼ 8.36 Hz, 2H), 8.01 (d, J ¼
8.33 Hz, 2H), 9.15 (s, 2H). 13C NMR (75 MHz, DMSO-d6) d 45.0,
53.1, 63.9, 112.5, 118.8, 125.7, 127.7, 128.5, 129.0, 129.4, 130.1,
132.5, 132.8, 138.0, 142.3, 148.5, 158.4, 163.2. HRMS (ESI) m/z
calcd for C20H19N7O5 (M + H)+ 438.1520, found 438.1523.
Data for (E)-methyl 2-(methoxyimino)-2-(2-((2-(4-chlor-
obenzylidene)-1-(N-nitrocarbamimidoyl)hydrazinyl)methyl)
Data for (E)-methyl 2-(methoxyimino)-2-(2-((2-heptylidene-1-
(N-nitrocarbamimidoyl)hydrazinyl)methyl)phenyl)acetate
(6-
1
ꢂ
04). Yield 21%; white solid; mp 97–99 C; H NMR (300 MHz,
CDCl3) d 0.85 (t, J ¼ 6.70 Hz, 3H), 1.13–1.28 (m, 6H), 1.34–1.43
(m, 2H), 2.19–2.25 (m, 2H), 3.91 (s, 3H), 4.10 (s, 3H), 5.06 (s, 2H),
6.98–7.06 (m, 2H), 7.12–7.15 (m, 1H), 7.29 - 7.39 (m, 2H), 7.61 (s,
1H), 9.15 (s, 1H). 13C NMR (75 MHz, DMSO-d6) d 14.0, 22.1, 26.1,
28.1, 31.2, 32.4, 52.9, 63.5, 72.5, 125.6, 127.4, 128.6, 128.9, 129.2,
129.8, 132.8, 148.6, 158.4, 162.8. HRMS (ESI) m/z calcd for
C
19H28N6O5 (M + H)+ 421.2194, found 421.2193.
Data for (E)-methyl 2-(methoxyimino)-2-(2-((1-(N-
nitrocarbamimidoyl)-2-(propan-2-ylidene)hydrazinyl)methyl)
phenyl)acetate (6-05). Yield 24%; yellowish solid; mp 137–139
ꢂC; 1H NMR (300 MHz, CDCl3) d 1.42 (s, 6H), 3.89 (s, 3H), 4.09 (s,
ꢂ
phenyl)acetate (6-10). Yield 18%; white solid; mp 223–225 C;
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1H NMR (300 MHz, DMSO-d6) d 3.84 (s, 3H), 4.04 (s, 3H), 5.16 (s, 2H), 7.02–7.82 (m, 9H), 7.70 (s, 1H), 9.02 (br s, 2H). 13C NMR (75
2H), 7.02–7.86 (m, 8H), 7.66 (s, 1H), 9.10 (br s, 2H). 13C NMR (75 MHz, DMSO-d6) d 21.3, 53.1, 63.9, 125.6, 127.6, 128.0, 129.0,
MHz, DMSO-d6) d 44.8, 53.1, 63.9, 125.7, 127.6, 129.0, 129.3, 129.2, 129.5, 130.0, 131.0, 132.8, 140.7, 144.4, 148.5, 158.4,
129.7, 130.0, 132.6, 132.7, 136.3, 143.0, 148.5, 158.4, 163.1. 163.1. HRMS (ESI) m/z calcd for C20H22N6O5 (M + H)+ 427.1724,
HRMS (ESI) m/z calcd for C19H19ClN6O5 (M + H)+ 447.1178, found 427.1722.
found 447.1174.
Data for (E)-methyl 2-(methoxyimino)-2-(2-((2-(4-methoxy-
Data for (E)-methyl 2-(methoxyimino)-2-(2-((2-(2-chlor- benzylidene)-1-(N-nitrocarbamimidoyl)hydrazinyl)methꢂyl)
obenzylidene)-1-(N-nitrocarbamimidoyl)hydrazinyl)methyl) phenyl)acetate (6-17). Yield 28%; white solid; mp 213–215 C;
phenyl)acetate (6-11). Yield 22%; yellowish solid; mp 195–197 1H NMR (300 MHz, DMSO-d6) d 3.78 (s, 3H), 3.84 (s, 3H), 4.04 (s,
ꢂC; 1H NMR (300 MHz, DMSO-d6) d 3.77 (s, 3H), 3.98 (s, 3H), 5.24 3H), 5.14 (s, 2H), 6.95–7.76 (m, 8H), 7.62 (s, 1H), 9.02 (br s, 2H).
(s, 2H), 7.06–8.41 (m, 8H), 7.95 (s, 1H), 9.09 (br s, 2H). 13C NMR 13C NMR (75 MHz, DMSO-d6) d 44.6, 53.1, 55.6, 63.9, 114.4,
(75 MHz, DMSO-d6) d 45.5, 52.9, 63.8, 126.1, 127.5, 127.6, 128.5, 126.3, 127.6, 129.0, 129.2, 129.8, 130.0, 132.9, 144.3, 148.5,
129.2, 129.3, 129.9, 129.9, 131.0, 132.0, 132.2, 133.6, 140.3, 158.3, 161.4, 163.1. HRMS (ESI) m/z calcd for C20H22N6O6 (M +
148.4, 158.3, 162.6. HRMS (ESI) m/z calcd for C19H19ClN6O5 (M + H)+ 443.1674, found 443.1671.
H)+ 447.1178, found 447.1172.
Data for (E)-methyl 2-(methoxyimino)-2-(2-((2-(3-methoxy-
Data for (E)-methyl 2-(methoxyimino)-2-(2-((2-(2,4-dichlor- benzylidene)-1-(N-nitrocarbamimidoyl)hydrazinyl)methyl)
obenzylidene)-1-(N-nitrocarbamimidoyl)hydrazinyl)methyl) phenyl)acetate (6-18). Yield 33%; pink solid; mp 214–216 ꢂC; 1H
phenyl)acetate (6-12). Yield 47%; grey solid; mp 184–186 ꢂC; 1H NMR (300 MHz, DMSO-d6) d 3.79 (s, 3H), 3.84 (s, 3H), 4.05 (s,
NMR (300 MHz, DMSO-d6) d 3.76 (s, 3H), 3.97 (s, 3H), 5.24 (s, 3H), 5.15 (s, 2H), 6.97–7.44 (m, 8H), 7.64 (s, 1H), 9.06 (br s, 2H).
2H), 7.07 (d, J ¼ 7.41, 1H), 7.23 (dd, J1 ¼ 1.32, J2 ¼ 7.38, 1H), 13C NMR (75 MHz, DMSO-d6) d 44.7, 53.1, 55.5, 63.9, 112.4,
7.33–7.50 (m, 3H), 7.63 (d, J ¼ 2.07, 1H), 7.87 (s, 1H), 8.46 (d, J ¼ 116.7, 121.1, 125.6, 127.6, 129.0, 129.3, 130.0, 132.8, 135.0,
8.64, 1H), 9.13 (s, 2H). 13C NMR (75 MHz, DMSO-d6) d 45.6, 52.9, 144.4, 148.5, 158.4, 159.8, 163.2. HRMS (ESI) m/z calcd for
63.8, 126.1, 127.6, 127.9, 129.2, 129.3, 129.7, 129.8, 130.1, 132.1,
C
20H22N6O6 (M + H)+ 443.1674, found 443.1668.
134.3, 135.8, 139.2, 148.4, 158.3, 162.6. HRMS (ESI) m/z calcd for
Data for (E)-methyl 2-(2-((2-(2-methoxybenzylidene)-1-(N-
C
19H18Cl2N6O5 (M + H)+ 481.0789, found 481.0784.
nitrocarb-amimidoyl)hydrazinyl)methyl)phenyl)-2-(methoxyimino)
Data for (E)-methyl 2-(methoxyimino)-2-(2-((2-(4-nitro- acetate (6-19). Yield 29%; yellowish solid; mp 186–188 ꢂC; 1H NMR
benzylidene)-1-(N-nitrocarbamimidoyl)hydrazinyl)methyl) (300 MHz, CDCl3) d 3.74 (s, 3H), 3.89 (s, 3H), 4.11 (s, 3H), 5.25 (s,
ꢂ
phenyl)acetate (6-13). Yield 20%; yellow solid; mp 212–214 C; 2H), 6.86–6.89 (m, 1H), 6.98–7.06 (m, 2H), 7.18–7.20 (m, 1H), 7.32–
1H NMR (300 MHz, DMSO-d6) d 3.85 (s, 3H), 4.05 (s, 3H), 5.20 (s, 7.40 (m, 3H), 7.69–7.73 (dd, J1 ¼ 1.68, J2 ¼ 7.74, 1H), 7.73 (s, 1H),
2H), 7.05–8.26 (m, 8H), 7.76 (s, 1H), 9.20 (br s, 2H). 13C NMR (75 8.06 (s, 1H), 9.22 (s, 1H). 13C NMR (75 MHz, DMSO-d6) d 45.0, 52.9,
MHz, DMSO-d6) d 45.0, 53.1, 63.9, 124.1, 125.7, 127.7, 128.9, 56.0, 63.8, 112.0, 120.8, 121.8, 125.8, 127.1, 127.4, 129.2, 129.8,
129.1, 129.4, 130.1, 132.5, 139.8, 141.8, 148.2, 148.5, 158.4, 132.6, 148.5, 158.1, 158.3, 162.7. HRMS (ESI) m/z calcd for
163.1. HRMS (ESI) m/z calcd for C19H19N7O7 (M + H)+ 458.1419, C20H22N6O6 (M + H)+ 443.1674, found 443.1672.
found 458.1416.
Data for (E)-methyl 2-(methoxyimino)-2-(2-((2-(benzo[d][1,3]
Data for (E)-methyl 2-(methoxyimino)-2-(2-((2-(3-nitro- dioxol-5-ylmethylene)-1-(N-nitrocarbamimidoyl)hydrazinyl)
benzylidene)-1-(N-nitrocarbamimidoyl)hydrazinyl)methyl) methyl)phenyl)acetate (6-20). Yield 26%; white solid; mp 208–
phenyl)acetate (6-14). Yield 30%; yellowish solid; mp 118–120 210 ꢂC; 1H NMR (300 MHz, DMSO-d6) d 3.84 (s, 3H), 4.04 (s, 3H),
ꢂC; 1H NMR (300 MHz, DMSO-d6) d 3.86 (s, 3H), 4.04 (s, 3H), 5.19 5.13 (s, 2H), 6.03 (s, 2H), 6.90–7.81 (m, 7H), 7.57 (s, 1H), 9.05 (br
(s, 2H), 7.06–8.58 (m, 8H), 7.79 (s, 1H), 9.22 (br s, 2H). 13C NMR s, 2H). 13C NMR (75 MHz, DMSO-d6) d 44.6, 53.1, 63.9, 101.8,
(75 MHz, DMSO-d6) d 44.9, 53.0, 59.9, 63.8, 122.5, 124.8, 125.8, 105.9, 108.4, 125.7, 127.6, 128.3, 129.0, 129.2, 130.0, 132.9,
127.7, 129.0, 129.4, 130.0, 130.4, 132.6, 133.7, 135.4, 142.1, 144.2, 148.4, 148.5, 149.6, 158.3, 163.1. HRMS (ESI) m/z calcd for
148.5, 158.4, 163.2. HRMS (ESI) m/z calcd for C19H19N7O7 (M +
C
20H20N6O7 (M + H)+ 457.1466, found 457.1461.
Data for (E)-methyl 2-(methoxyimino)-2-(2-((1-(N-nitrocarba
H)+ 458.1419, found 458.1415.
Data for (E)-methyl 2-(2-(((E)-2-(4-(tert-butyl)benzylidene)- mimidoyl)-2-(3-phenoxy benzylidene)hydrazinyl)methyl)phenyl)
1
ꢂ
1-(N-nitrocarbamimidoyl)hydrazinyl)methyl)phenyl)-2- acetate (6-21). Yield 38%; white solid; mp 189–191 C; H NMR
(methoxyimino)acetate (6-15). Yield 25%; yellowish solid; mp (300 MHz, DMSO-d6) d 3.77 (s, 3H), 3.99 (s, 3H), 5.15 (s, 2H),
205–207 ꢂC; 1H NMR (300 MHz, DMSO-d6) d 1.27 (s, 9H), 3.84 (s, 6.98–7.64 (m, 13H), 7.52 (s, 1H), 9.07 (br s, 2H). 13C NMR (75
3H), 4.05 (s, 3H), 5.16 (s, 2H), 7.02 (d, J ¼ 7.68, 1H), 7.24 (dd, J1 ¼ MHz, DMSO-d6) d 44.7, 53.0, 63.8, 118.0, 118.6, 121.0, 123.7,
1.38, J2 ¼ 7.17, 1H), 7.31–7.44 (m, 4H), 7.64 (s, 1H), 7.71 (d, J ¼ 123.7, 125.7, 127.6, 129.0, 129.3, 130.0, 130.3, 130.6, 132.7,
8.40, 2H), 9.03 (s, 2H). 13C NMR (75 MHz, DMSO-d6) d 31.1, 34.8, 135.8, 143.7, 148.5, 156.9, 157.1, 158.4, 163.1. HRMS (ESI) m/z
44.6, 53.1, 63.9, 125.6, 125.7, 127.6, 127.9, 129.0, 129.3, 130.0, calcd for C25H24N6O6 (M + H)+ 505.1830, found 505.1822.
131.0, 132.7, 144.5, 148.6, 153.6, 158.4, 163.1. HRMS (ESI) m/z
Data for (E)-methyl 2-(methoxyimino)-2-(2-((2-(3-hydroxy-
calcd for C23H28N6O5 (M + H)+ 469.2194, found 469.2193.
benzylidene)-1-(N-nitrocarbamimidoyl)hydrazinyl)methyl)
ꢂ
Data for (E)-methyl 2-(methoxyimino)-2-(2-((2-(4-methyl- phenyl)acetate (6-22). Yield 14%; white solid; mp 202–204 C;
benzylidene)-1-(N-nitrocarbamimidoyl)hydrazinyl)methyl) 1H NMR (300 MHz, DMSO-d6) d 3.84 (s, 3H), 4.04 (s, 3H), 5.15 (s,
ꢂ
phenyl)acetate (6-16). Yield 35%; white solid; mp 211–213 C; 2H), 6.80–7.42 (m, 8H), 7.57 (s, 1H), 9.03 (br s, 2H), 9.59 (s, 1H).
1H NMR (300 MHz, DMSO-d6) d 3.84 (s, 3H), 4.03 (s, 3H), 5.17 (s, 13C NMR (75 MHz, DMSO-d6) d 44.7, 53.0, 63.9, 114.4, 117.9,
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119.0, 125.6, 127.5, 129.0, 129.2, 129.9, 130.0, 132.7, 134.9,
Conflict of interest
144.6, 148.5, 157.8, 158.4, 163.0. HRMS (ESI) m/z calcd for
C
19H20N6O6 (M + H)+ 429.1517, found 429.1515.
The authors declare no competing nancial interest.
Data for (E)-methyl 2-(methoxyimino)-2-(2-((2-(2-hydroxy-
benzylidene)-1-(N-nitrocarbamimidoyl)hydrazinyl)methyl)
phenyl)acetate (6-23). Yield 36%; white solid; mp 184–186 C;
Acknowledgements
ꢂ
1H NMR (300 MHz, DMSO-d6) d 3.82 (s, 3H), 4.02 (s, 3H), 5.14 (s,
2H), 6.80–8.12 (m, 8H), 7.97 (s, 1H), 8.96 (br s, 2H), 9.93 (s, 1H).
13C NMR (75 MHz, DMSO-d6) d 44.8, 53.0, 63.8, 116.3, 119.4,
120.2, 125.5, 127.3, 127.4, 129.1, 129.8, 132.1, 132.6, 140.6,
148.5, 156.8, 158.3, 162.7. HRMS (ESI) m/z calcd for C19H20N6O6
(M + Na)+ 451.1337, found 451.1340.
This work was supported by the National Natural Science
Foundation of China (grant 31272076).
Notes and references
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