Synthesis and bioactivity of novel N,N′-diacylhydrazine derivatives containing furan(III)

Article abstract of DOI:10.1002/cjoc.201090218

42 novel diacylhydrazine derivatives containing furan were synthesized by the reaction of 5-substituted phenyl-2-furoyl chloride with substituted benzohydrazide in anhydrous dichloromethane under reflux. Their structures were confirmed by IR, ¹

Full text of DOI:10.1002/cjoc.201090218

FULL PAPER
Synthesis and Bioactivity of Novel N,N′-Diacylhydrazine
Derivatives Containing Furan (III)
Cui, Zining(崔紫宁)
Zhang, Li(张莉)
Huang, Juan(黄娟)
Yang, Xinling(杨新玲)
Ling, Yun*(凌云)
Department of Applied Chemistry, College of Science, China Agricultural University, Key Laboratory of Pesticide
Chemistry and Application, Ministry of Agriculture, Beijing 100193, China
42 novel diacylhydrazine derivatives containing furan were synthesized by the reaction of 5-substituted
phenyl-2-furoyl chloride with substituted benzohydrazide in anhydrous dichloromethane under reflux. Their struc-
tures were confirmed by IR, 1H NMR, MS and elemental analysis. Insecticidal and antitumor activity of these new
compounds was evaluated. The preliminary bioassays showed that the target compounds exhibited larvicidal activ-
ity to the Mythimna separate, some of them exhibited good or moderate larvicidal activity. At the concentration of
0.1%, compounds I2, I4, I5, and III1 showed 95.0%, 90.0%, 95.0% and 95.0% larvicidal activity to Mythimna
separate respectively. Some compounds such as I2, I4, I5 and III1 showed the typical IGRs’ activity, which could
induce the larvae premature, abnormal, and lethal larval molt. Results of anticancer activity indicated that some
compounds exhibited potential activity against some human cancer cell lines, for example, I1 and IV showed good
activity to the BGC-823 and the inhibitory rates were 60.86% and 61.94% respectively at 10 µmol/L.
Keywords diacylhydrazine, furan, insecticidal activity, antitumor activity
Introduction
(chromafenozide)14-18 and JS-11819,20 have been com-
mercialized in recent years. However, poor solubility
and cuticular penetration lead these compounds to low
contact toxicity.21-23 These disadvantages restricted their
field application. Lots of researches have been done to
improve the disadvantages.24-27
Our group also made some efforts in this area. The
furan ring was introduced to improve the solubility and
the bioactivity. The previous work showed that the sort
and substituted position of R2 on the benzene ring were
important to the insecticidal activity of the target com-
pounds. It was also found that this kind of compound
exhibited antitumor activity.28,29 In order to find the fur-
ther relationship between the structures and activities,
the different sorts of atoms at the different positions of
the benzene ring were introduced and the benzoyl group
was changed to isonicotinoyl and tosyl groups with the
purpose of testing the new novel compounds for insecti-
cidal and antitumor activity.
Insect growth regulators (IGRs), interfering the
normal molting and growth of insects, are regarded as
“the ideal pesticides in 21st century” owing to their
good selectivity, high potency and low toxicity to
mammals and non-target organisms.1-3 IGRs are there-
fore playing an important role in the system of inte-
grated pest management (IPM). However, the resistance
and narrow-spectrum activity of the IGRs are not fa-
vorable for their application.4 It is necessary to find new
IGRs for the sustainable development in agriculture.
As a new class of insect growth regulators, diacyl-
hydrazines appear to exert their insecticidal effect by
functioning as nonsteroidal ecdysone agonists that
mimic the action of 20-hydroxyecdysone (20E). The
20E receptor is a heterodimeric complex of two proteins:
ecdysone receptor protein (EcR) and ultraspiracle
(USP).5-8 Inappropriate activation of the ecdysone re-
ceptor leads to lethal premature molting. The first dia-
cylhydrazine IGR, N-tert-butyl-N,N'-dibenzoylhydra-
zine (RH-5849) which showed good activity against
Lepidopterans and low toxicity to mammals and
non-target organisms, was discovered in 1988.9,10 Sub-
sequently, RH-5992 (tebufenozide),11 RH-0345 (halo-
fenozide),12 RH-2485 (methoxyfenozide),13 ANS-118
Experimental
Materials and methods
All the melting points were determined with a
Cole-Parmer melting point apparatus while the ther-
*
E-mail: lyun@cau.edu.cn
Received December 15, 2009; revised and accepted March 17, 2010.
Project supported by the National Key Project for Basic Research (Nos. 2003CB114400, 2010CB126104), the National Natural Science Foundation
of China (Nos. 20672138, 20802089, 20972185), the National High Technology Research and Development Program of China (No.
2006AA10A201), the Scientific Research Foundation of Graduate School of China Agricultural University, and the State Key Laboratory of Ele-
mento-organic Chemistry.
Chin. J. Chem. 2010, 28, 1257— 1266
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Cui et al.
FULL PAPER
mometer was uncorrected. IR spectra were recorded on
1
a Shimadzu IR-435 spectrometer with KBr pellets. H
NMR spectra were recorded on a Bruker DPX300 in-
strument, while tetramethylsilane was used as the inter-
nal standards. Elemental analysis was performed by the
Analytical Center in the Institute of Chemistry, Chinese
Academy of Sciences, using a Flash EA 1112 elemental
analyzer. Mass spectra were measured on a Bruker
ESQUIRE-LC spectrometer.
The solvents and reagents were mainly purchased
from the Beijing Chemical Reagents Co., P. R. China.
The key intermediates, substituted benzohydrazides 1,
tosylhydrazine 2 and isonicotinohydrazide 3 were pre-
pared according to the known method28-30 and their
structures are shown in Figure 1. 5-Substituted
phenyl-2-furoic acid 4 was prepared according to the
method given in references.28,31,32
Figure 1 The key intermediates.
General procedure for the preparation of target
compounds I— III
A mixture of 5-substituted phenyl-2-furoic acid (0.05
mol) and thionyl chloride (0.15 mol) was refluxed in
Scheme 1 Synthetic route of target compounds I— IV
1258
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Chin. J. Chem. 2010, 28, 1257— 1266

Synthesis and Bioactivity of Novel N,N′-Diacylhydrazine Derivatives
anhydrous benzene for 3 h. The excess of thionyl chlo-
ride and the solvent were distilled off, and the residue
was dissolved in anhydrous dichloromethane. The re-
sultant solution was added into substituted acylhy-
drazide. The mixture was stirred and refluxed for 4 h.
After cooling, the solid was filtered and recrystallized
from ethyl acetate to obtain the target compounds I—III.
2H, ArH), 8.00—8.04 (m, 2H, ArH-Fu), 10.37 (s, 1H,
NH), 10.48 (s, 1H, NH); IR (KBr) ν: 3400, 1610, 1520,
－
1
1470, 1380, 1020 cm . Anal. calcd for C19H15N3O6: C
59.84, H 3.96, N 11.02; found C 59.85, H 4.00, N 11.02.
N-(4-Ethoxybenzoyl)-N'-[5-(2'-nitrophenyl)-2-furoyl]-
hydrazine (I5): Yellow powdery crystals, yield 74.3%,
1
m.p. 172—173 ℃. H NMR (DMSO-d6, 300 MHz) δ:
1.35 (t, J＝6.98 Hz, 3H, CH3-C-O), 4.11 (q, J＝6.96 Hz,
2H, O-CH2-C), 6.96 (d, J＝3.63 Hz, 1H, FuH), 7.04 (d,
J＝8.88 Hz, 2H, ArH), 7.39 (d, J＝3.66 Hz, 1H, FuH),
7.69 (td, J＝7.76, 1.36 Hz, 1H, ArH-Fu), 7.83 (td, J＝
7.68, 1.27 Hz, 1H, ArH-Fu), 7.89 (dd, J＝6.99, 1.88 Hz,
2H, ArH), 8.00—8.04 (m, 2H, ArH-Fu), 10.36 (s, 1H,
NH), 10.49 (s, 1H, NH); IR (KBr) ν: 3200, 1680, 1640,
The procedure for the preparation of target com-
pound IV
Half mole amount of the hydrazine monohydrate
was added into the solution of 5-(4'-chlorophenyl)-2-
furoyl chloride in anhydrous dichloromethane dropwise.
Then the mixture was stirred and refluxed for 4 h. After
cooling, the solid was filtered and recrystallized from
ethyl acetate to obtain the target compound IV.
－
1
1600, 1520, 1370, 1260, 1190, 1110, 1020 cm . Anal.
calcd for C20H17N3O6: C 60.76, H 4.33, N 10.63; found
C 60.50, H 4.38, N 10.66.
The yields and melting points of the target com-
pounds were listed as follows. Their structures were
confirmed by IR, 1H NMR, MS and elemental analysis.
N-Benzoyl-N'-[5-(4'-chlorophenyl)-2-furoyl]hydrazi-
ne (I1): White powdery crystals, yield 60.9%, m.p.
N-(4-Bromobenzoyl)-N'-[5-(2'-nitrophenyl)-2-furoyl]-
hydrazine (I6): Light yellow powdery crystals, yield
1
57.6%, m.p. 196—197 ℃. H NMR (DMSO-d6, 300
MHz) δ: 6.96 (d, J＝3.66 Hz, 1H, FuH), 7.40 (d, J＝
3.66 Hz, 1H, FuH), 7.67—7.87 (m, 6H, 2ArH-Fu＋
4ArH), 8.00—8.04 (m, 2H, ArH-Fu), 10.59 (s, 1H, NH),
10.62 (s, 1H, NH); IR (KBr) ν: 3200, 1670, 1640, 1580,
1
175—176 ℃. H NMR (DMSO-d6, 300 MHz) δ: 7.22
(d, J＝3.63 Hz, 1H, FuH), 7.34 (d, J＝3.63 Hz, 1H,
FuH), 7.51—7.64 (m, 5H, 3ArH＋2ArH-Fu), 7.92—
8.02 (m, 4H, 2ArH＋2ArH-Fu), 10.51 (s, 1H, NH),
10.59 (s, 1H, NH); IR (KBr) ν: 3100, 2800, 1610, 1580,
－
1
1520, 1460, 1360, 1340, 1290, 1260, 1110, 1010 cm .
Anal. calcd for C18H12BrN3O5: C 50.25, H 2.81, N 9.77;
found C 50.16, H 2.89, N 9.75.
－
1
1480, 1290, 1270 cm . Anal. calcd for C18H13ClN2O3:
C 63.44, H 3.85, N 8.22; found C 63.33, H 3.91, N 8.22.
N-(4-Chlorobenzoyl)-N'-[5-(2'-nitrophenyl)-2-furoyl]-
hydrazine (I2): Light yellow powdery crystals, yield
N-(4-Methylbenzoyl)-N'-[5-(2'-nitrophenyl)-2-furoyl]-
hydrazine (I7): Light yellow powdery crystals, yield
1
74.8%, m.p. 208—209 ℃. H NMR (DMSO-d6, 300
1
79.8%, m.p. 193—194 ℃. H NMR (DMSO-d6, 300
MHz) δ: 2.38 (s, 3H, CH3), 6.96 (d, J＝3.66 Hz, 1H,
FuH), 7.33 (d, J＝8.10 Hz, 2H, ArH), 7.39 (d, J＝3.66
Hz, 1H, FuH), 7.69 (td, J＝7.83, 1.29 Hz, 1H, ArH-Fu),
7.81—7.86 (m, 3H, ArH-Fu＋2ArH), 8.00—8.04 (m,
2H, ArH-Fu), 10.44 (s, 1H, NH), 10.52 (s, 1H, NH); IR
(KBr) ν: 3200, 1630, 1520, 1460, 1360, 1340, 1280,
MHz) δ: 6.96 (d, J＝3.66 Hz, 1H, FuH), 7.40 (d, J＝
3.66 Hz, 1H, FuH), 7.60—7.64 (m, 2H, ArH), 7.70 (td,
J＝7.77, 1.34 Hz, 1H, ArH-Fu), 7.84 (td, J＝7.65, 1.23
Hz, 1H, ArH-Fu), 7.91—7.95 (m, 2H, ArH), 8.00—8.04
(m, 2H, ArH-Fu), 10.59 (s, 1H, NH), 10.62 (s, 1H, NH);
IR (KBr) ν: 3200, 2800, 1630, 1590, 1510, 1470, 1370,
－
1
1260, 1110 cm . Anal. calcd for C19H15N3O5: C 62.46,
H 4.14, N 11.50; found C 62.18, H 4.12, N 11.56.
N-(4-Chlorobenzoyl)-N'-[5-(4'-nitrophenyl)-2-furoyl]-
hydrazine (I8): Light yellow powdery crystals, yield
－
1
1290, 1250, 1090 cm . Anal. calcd for C18H12ClN3O5:
C 56.04, H 3.14, N 10.89; found C 55.92, H 3.11, N
10.87.
1
N-(2-Chlorobenzoyl)-N'-[5-(2'-nitrophenyl)-2-furoyl]-
hydrazine (I3): Yellow powdery crystals, yield 77.1%,
71.9%, m.p. 247—248 ℃. H NMR (DMSO-d6, 300
MHz) δ: 7.41 (d, J＝3.69 Hz, 1H, FuH), 7.50 (d, J＝
3.66 Hz, 1H, FuH), 7.63 (dd, J＝6.69, 1.95 Hz, 2H,
ArH), 7.95 (dd, J＝6.69, 1.95 Hz, 2H, ArH), 8.24 (dd,
J＝7.05, 2.03 Hz, 2H, ArH-Fu), 8.33—8.38 (m, 2H,
ArH-Fu), 10.67 (s, 1H, NH), 10.77 (s, 1H, NH); IR
1
m.p. 169—170 ℃. H NMR (DMSO-d6, 300 MHz) δ:
6.97 (d, J＝3.66 Hz, 1H, FuH), 7.41 (d, J＝3.69 Hz, 1H,
FuH), 7.47—7.58 (m, 4H, ArH), 7.69 (td, J＝7.77, 1.38
Hz, 1H, ArH-Fu), 7.83 (td, J＝7.67, 1.22 Hz, 1H,
ArH-Fu), 8.00—8.05 (m, 2H, ArH-Fu), 10.44 (s, 1H,
NH), 10.68 (s, 1H, NH); IR (KBr) ν: 3200, 1690, 1640,
－
1
(KBr) ν: 3300, 2960, 1670, 1600, 1520, 1340 cm .
Anal. calcd for C18H12ClN3O5: C 56.04, H 3.14, N 10.89;
found C 55.84, H 3.24, N 10.59.
－
1
1580, 1520, 1470, 1360, 1290 cm . Anal. calcd for
C18H12ClN3O5: C 56.04, H 3.14, N 10.89; found C
56.09, H 3.23, N 10.72.
N-(2-Chlorobenzoyl)-N'-[5-(4'-nitrophenyl)-2-furoyl]-
hydrazine (I9): Brown powdery crystals, yield 60.0%,
1
N-(4-Methoxybenzoyl)-N'-[5-(2'-nitrophenyl)-2-furo-
yl]hydrazine (I4): Yellow powdery crystals, yield 69.7%,
m.p. 208—209 ℃. H NMR (DMSO-d6, 300 MHz) δ:
7.41 (d, J＝3.69 Hz, 1H, FuH), 7.46—7.60 (m, 5H,
FuH＋4ArH), 8.20—8.31 (m, 2H, ArH-Fu), 8.33—8.38
(m, 2H, ArH-Fu), 10.49 (brs, 1H, NH), 10.86 (brs, 1H,
NH); IR (KBr) ν: 3200, 2960, 1700, 1650, 1600, 1580,
1
m.p. 197—198 ℃. H NMR (DMSO-d6, 300 MHz) δ:
3.84 (s, 3H, OCH3), 6.95 (d, J＝3.63 Hz, 1H, FuH),
7.06 (d, J＝8.85 Hz, 2H, ArH), 7.38 (d, J＝3.66 Hz, 1H,
FuH), 7.70 (td, J＝7.77, 1.17 Hz, 1H, ArH-Fu), 7.83 (td,
J＝7.65, 1.04 Hz, 1H, ArH-Fu), 7.90 (d, J＝8.82 Hz,
－
1
1510, 1340, 1280 cm . Anal. calcd for C18H12ClN3O5:
C 56.04, H 3.14, N 10.89; found C 55.81, H 3.27, N
Chin. J. Chem. 2010, 28, 1257— 1266
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Cui et al.
FULL PAPER
10.68.
N-(4-Methoxybenzoyl)-N'-[5-(4'-nitrophenyl)-2-furo-
yl]hydrazine (I10): Yellow powdery crystals, yield
1
yield 65.6%, m.p. 217—218 ℃. H NMR (DMSO-d6,
300 MHz) δ: 1.36 (t, J＝6.92 Hz, 3H, CH3-C-O), 4.12
(q, J＝6.92 Hz, 2H, O-CH2-C), 7.03—7.06 (m, 2H,
ArH), 7.24 (d, J＝3.60 Hz, 1H, FuH), 7.33 (d, J＝3.63
Hz, 1H, FuH), 7.70 (dd, J＝6.87, 1.80 Hz, 2H, ArH-Fu),
7.89—7.95 (m, 4H, 2ArH-Fu＋2ArH), 10.36 (s, 1H,
NH), 10.54 (s, 1H, NH); IR (KBr) ν: 3200, 2900, 1630,
1
75.1%, m.p. 237—238 ℃. H NMR (DMSO-d6, 300
MHz) δ: 3.84 (s, 3H, OCH3), 7.07 (d, J＝8.85 Hz, 2H,
ArH), 7.40 (d, J＝3.69 Hz, 1H, FuH), 7.50 (d, J＝3.66
Hz, 1H, FuH), 7.92 (d, J＝8.88 Hz, 2H, ArH), 8.24 (d,
J＝9.03 Hz, 2H, ArH-Fu), 8.36 (d, J＝9.03 Hz, 2H,
ArH-Fu), 10.56 (brs, 2H, NHNH); IR (KBr) ν: 3300,
－
1
1600, 1490, 1470, 1250, 1170, 1090, 1030 cm . Anal.
calcd for C20H17BrN2O4: C 55.96, H 3.99, N 6.53; found
C 56.13, H 4.01, N 6.71.
－
1
3100, 1620, 1580, 1480, 1420, 1330, 1240 cm . Anal.
calcd for C19H15N3O6: C 59.84, H 3.96, N 11.02; found
C 59.61, H 3.98, N 11.33.
N-(4-Bromobenzoyl)-N'-[5-(4'-bromophenyl)-2-furo-
yl]hydrazine (I16): White powdery crystals, yield
1
N-(4-Ethoxybenzoyl)-N'-[5-(4'-nitrophenyl)-2-furoyl]-
hydrazine (I11): Yellow powdery crystals, yield 85.2%,
64.7%, m.p. 251—252 ℃. H NMR (DMSO-d6, 300
MHz) δ: 7.24 (d, J＝3.63 Hz, 1H, FuH), 7.34 (d, J＝
3.63 Hz, 1H, FuH), 7.69—7.79 (m, 4H, 2ArH-Fu＋
2ArH), 7.86—7.96 (m, 4H, 2ArH-Fu＋2ArH), 10.65 (s,
2H, NHNH); IR (KBr) ν: 3100, 2800, 1590, 1560, 1510,
1
m.p. 252—253 ℃. H NMR (DMSO-d6, 300 MHz) δ:
1.36 (t, J＝6.96 Hz, 3H, CH3-C-O), 4.12 (q, J＝6.96 Hz,
2H, O-CH2-C), 7.05 (d, J＝8.88 Hz, 2H, ArH), 7.40 (d,
J＝3.69 Hz, 1H, FuH), 7.50 (d, J＝3.66 Hz, 1H, FuH),
7.91 (d, J＝8.85 Hz, 2H, ArH), 8.24 (d, J＝9.00 Hz, 2H,
ArH-Fu), 8.35 (d, J＝9.03 Hz, 2H, ArH-Fu), 10.40 (brs,
1H, NH), 10.67 (brs, 1H, NH); IR (KBr) ν: 3200, 1680,
－
1
1480, 1450, 1270, 1080, 1010 cm . Anal. calcd for
C18H12Br2N2O3: C 46.58, H 2.61, N 6.04; found C 46.69,
H 2.74, N 6.28.
N-(4-Bromobenzoyl)-N'-[5-(3'-nitrophenyl)-2-furoyl]-
hydrazine (I17): Light yellow powdery crystals, yield
－
1
1640, 1600, 1520, 1350, 1260, 1180, 1100, 1010 cm .
Anal. calcd for C20H17N3O6: C 60.76, H 4.33, N 10.63;
found C 60.75, H 4.43, N 10.89.
1
67.5%, m.p. 243—243 ℃. H NMR (DMSO-d6, 300
MHz) δ: 7.38 (d, J＝3.66 Hz, 1H, FuH), 7.46 (d, J＝
3.66 Hz, 1H, FuH), 7.76—7.82 (m, 3H, ArH-Fu＋
2ArH), 7.86—7.90 (m, 2H, ArH), 8.21—8.24 (m, 1H,
ArH-Fu), 8.40 (d, J＝8.07 Hz, 1H, ArH-Fu), 8.82 (t, J＝
1.85 Hz, 1H, ArH-Fu), 10.65 (s, 1H, NH), 10.79 (s, 1H,
NH); IR (KBr) ν: 3200, 1610, 1590, 1560, 1510, 1440,
1330, 1260 cm－ 1. Anal. calcd for C18H12BrN3O5: C
50.25, H 2.81, N 9.77; found C 50.02, H 2.87, N 9.86.
N-(4-Chlorobenzoyl)-N'-[5-(2',4'-difluorophenyl)-2-
furoyl]hydrazine (I18): White powdery crystals, yield
N-(4-Chlorobenzoyl)-N'-[5-(4'-bromophenyl)-2-furo-
yl]hydrazine (I12): White powdery crystals, yield
1
62.2%, m.p. 246—247 ℃. H NMR (DMSO-d6, 300
MHz) δ: 7.24 (d, J＝3.63 Hz, 1H, FuH), 7.34 (d, J＝
3.66 Hz, 1H, FuH), 7.68—7.78 (m, 4H, 2ArH-Fu＋
2ArH), 7.85—7.89 (m, 2H, ArH-Fu), 7.94 (dd, J＝6.78,
1.83 Hz, ArH), 10.64 (s, 2H, NHNH); IR (KBr) ν: 3100,
－
1
2900, 1590, 1560, 1470, 1440, 1270, 1080 cm . Anal.
calcd for C18H12BrClN2O3: C 51.52, H 2.88, N 6.68;
found C 51.18, H 2.93, N 6.80.
1
66.8%, m.p. 225—225.5 ℃. H NMR (DMSO-d6, 300
N-(2-Chlorobenzoyl)-N'-[5-(4'-bromophenyl)-2-furo-
yl]hydrazine (I13): White powdery crystals, yield
MHz) δ: 6.99 (t, J＝3.74 Hz, 1H, FuH), 7.29—7.38 (m,
2H, FuH ＋ArH-Fu), 7.45—7.53 (m, 1H, ArH-Fu),
7.62—7.65 (m, 2H, ArH), 7.93—7.97 (m, 2H, ArH),
8.24—8.32 (m, 1H, ArH-Fu), 10.66 (s, 1H, NH), 10.70
(s, 1H, NH); IR (KBr) ν: 3200, 1610, 1570, 1520, 1490,
1
58.7%, m.p. 229—230 ℃. H NMR (DMSO-d6, 300
MHz) δ: 7.24 (d, J＝3.63 Hz, 1H, FuH), 7.34 (d, J＝
3.63 Hz, 1H, FuH), 7.46—7.57 (m, 4H, ArH),
7.69—7.72 (m, 2H, ArH-Fu), 7.94—7.97 (m, 2H,
ArH-Fu), 10.45 (s, 1H, NH), 10.73 (s, 1H, NH); IR
(KBr) ν: 3200, 1690, 1640, 1570, 1490, 1470, 1290,
－
1
1460, 1270, 1110,＋1080, 1010 cm ; MS/ESI m/z (%):
398.9 [M ＋Na]
(100). Anal. calcd for C18H11-
ClF2N2O3: C 57.38, H 2.94, N 7.44; found C 57.27, H
3.13, N 7.41.
N-(2-Chlorobenzoyl)-N'-[5-(2',4'-difluorophenyl)-2-
furoyl]hydrazine (I19): White powdery crystals, yield
－
1
1270, 1110, 1070 cm . Anal. calcd for C18H12BrClN2-
O3: C 51.52, H 2.88, N 6.68; found C 51.30, H 2.88, N
6.78.
N-(4-Methoxybenzoyl)-N'-[5-(4'-bromophenyl)-2-fu-
royl]hydrazine (I14): Light yellow powdery crystals,
1
52.1%, m.p. 196—197 ℃. H NMR (DMSO-d6, 300
MHz) δ: 6.99 (t, J＝3.72 Hz, 1H, FuH), 7.00—7.38 (m,
2H, FuH ＋ArH-Fu), 7.44—7.59 (m, 5H, 4ArH ＋
ArH-Fu), 8.26—8.34 (m, 1H, ArH-Fu), 10.48 (s, 1H,
NH), 10.78 (s, 1H, NH); IR (KBr) ν: 3200, 2900, 1690,
1640, 1590, 1530, 1490, 1410, 1290, 1280, 1110, 1100,
1
yield 80.3%, m.p. 213—214 ℃. H NMR (DMSO-d6,
300 MHz) δ: 3.84 (s, 3H, OCH3), 7.07 (d, J＝8.91 Hz,
2H, ArH), 7.24 (d, J＝3.60 Hz, 1H, FuH), 7.33 (d, J＝
3.63 Hz, 1H, FuH), 7.70 (dd, J＝6.81, 1.76 Hz, 2H,
ArH-Fu), 7.90—7.96 (m, 4H, 2ArH-Fu＋2ArH), 10.38
(s, 1H, NH), 10.55 (s, 1H, NH); IR (KBr) ν: 3300, 1690,
1640, 1590, 1490, 1470, 1290, 1280, 1250, 1180, 1100,
－
＋
1
1010 cm ; MS/ESI m/z (%): 398.9 [M＋Na] (100).
Anal. calcd for C18H11ClF2N2O3: C 57.38, H 2.94, N
7.44; found C 57.11, H 2.99, N 7.47.
－
1
1010 cm . Anal. calcd for C19H15BrN2O4: C 54.96, H
N-(4-Methoxybenzoyl)-N'-[5-(2',4'-difluorophenyl)-
2-furoyl]hydrazine (I20): Light pink powdery crystals,
3.64, N 6.75; found C 54.96, H 3.77, N 7.03.
N-(4-Ethoxybenzoyl)-N'-[5-(4'-bromophenyl)-2-furo-
yl]hydrazine (I15): White powde DMSO-d6, ry crystals,
1
yield 69.5%, m.p. 225—226 ℃. H NMR (DMSO-d6,
300 MHz) δ: 3.84 (s, 3H, OCH3), 6.99 (t, J＝3.74 Hz,
1260
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© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 1257— 1266

Synthesis and Bioactivity of Novel N,N′-Diacylhydrazine Derivatives
1H, FuH), 7.07 (d, J＝8.91 Hz, 2H, ArH), 7.29—7.32
(m, 1H, ArH-Fu), 7.36 (d, J＝3.63 Hz, 1H, FuH),
7.44—7.52 (m, 1H, ArH-Fu), 7.92 (dd, J＝6.90, 2.04
Hz, 2H, ArH), 8.24—8.32 (m, 1H, ArH-Fu), 10.40 (s,
1H, NH), 10.59 (s, 1H, NH); IR (KBr) ν: 3250, 1680,
300 MHz) δ: 7.04—7.06 (m, 1H, ArH-Fu), 7.28—7.33
(m, 2H, FuH＋ArH-Fu), 7.47 (d, J＝3.66 Hz, 1H, FuH),
7.54—7.64 (m, 3H, ArH-Fu＋2ArH), 7.91—7.96 (m,
2H, ArH), 10.52 (s, 1H, NH), 10.62 (s, 1H, NH); IR
－
1
(KBr) ν: 3200, 1600, 1560, 1470, 1280, 1090 cm ;
MS/ESI m/z (%): 398.9 [M＋Na]＋ (100). Anal. calcd
for C18H11ClF2N2O3: C 57.38, H 2.94, N 7.44; found C
57.23, H 3.04, N 7.54.
－
1
1650, 1600, 1540, 1490, 1410, 1260, 1160, 1010 cm ;
MS/ESI m/z (%): 394.9 [M＋Na]＋ (100). Anal. calcd
for C19H14F2N2O4: C 61.29, H 3.79, N 7.52; found C
61.25, H 3.81, N 7.66.
N-(4-Methoxybenzoyl)-N'-[5-(2',6'-difluorophenyl)-
2-furoyl]hydrazine (I26): Light yellow powdery crystals,
N-(4-Bromobenzoyl)-N'-[5-(2',4'-difluorophenyl)-2-
furoyl]hydrazine (I21): White powdery crystals, yield
1
yield 73.8%, m.p. 201—202 ℃. H NMR (DMSO-d6,
1
73.0%, m.p. 238—239 ℃. H NMR (DMSO-d6, 300
300 MHz) δ: 3.84 (s, 3H, CH3), 7.03—7.09 (m, 3H,
ArH-Fu＋2ArH), 7.27—7.33 (m, 2H, FuH＋ArH-Fu),
7.47 (d, J＝3.66 Hz, 1H, FuH), 7.51—7.59 (m, 1H,
ArH-Fu), 7.90—7.94 (m, 2H, ArH), 10.39 (s, 1H, NH),
10.43 (s, 1H, NH); IR (KBr) ν: 3600, 1690, 1650, 1590,
MHz) δ: 6.99 (t, J＝3.72 Hz, 1H, FuH), 7.30—7.38 (m,
2H, FuH ＋ArH-Fu), 7.45—7.52 (m, 1H, ArH-Fu),
7.76—7.79 (m, 2H, ArH), 7.86—7.89 (m, 2H, ArH),
8.24—8.32 (m, 1H, ArH-Fu), 10.66 (s, 1H, NH), 10.69
(s, 1H, NH); IR (KBr) ν: 3200, 1660, 1610, 1560, 1510,
－
1
1530, 1490, 1480, 1270, 1180, 1010 cm . Anal. calcd
for C19H14F2N2O4: C 61.29, H 3.79, N 7.52; found C
61.23, H 3.83, N 7.65.
－
1
1490, 1450, 1360, 1270, 1130, 1110, 1060, 1010 cm ;
MS/ESI m/z (%): 444.7 [M＋Na]＋ (100). Anal. calcd
for C18H11F2N2O3: C 51.33, H 2.63, N 6.65; found C
50.95, H 2.63, N 6.68.
N-(4-Bromobenzoyl)-N'-[5-(2',6'-difluorophenyl)-2-
furoyl]hydrazine (I27): Yellow powdery crystals, yield
1
N-(4-Methylbenzoyl)-N'-[5-(2',4'-difluorophenyl)-2-
furoyl]hydrazine (I22): Light yellow powdery crystals,
78.9%, m.p. 207—208 ℃. H NMR (DMSO-d6, 300
MHz) δ: 7.04—7.06 (m, 1H, ArH-Fu), 7.28—7.33 (m,
2H, FuH＋ArH-Fu), 7.47 (d, J＝3.66 Hz, 1H, FuH),
7.54—7.59 (m, 1H, ArH-Fu), 7.75—7.78 (m, 2H, ArH),
7.84—7.88 (m, 2H, ArH), 10.52 (s, 1H, NH), 10.62 (s,
1H, NH); IR (KBr) ν: 3200, 1600, 1570, 151＋0, 1470,
1
yield 68.1%, m.p. 182—183 ℃. H NMR (DMSO-d6,
300 MHz) δ: 2.39 (s, 3H, CH3), 6.99 (t, J＝3.74 Hz, 1H,
FuH), 7.29—7.37 (m, 4H, FuH＋2ArH＋ArH-Fu),
7.44—7.52 (m, 1H, ArH-Fu), 7.84 (d, J＝8.19 Hz, 2H,
ArH), 8.24—8.33 (m, 1H, ArH-Fu), 10.47 (s, 1H, NH),
10.63 (s, 1H, NH); IR (KBr) ν: 3200, 1610, 1570, 1520,
－
1
1280 cm ; MS/ESI m/z (%): 444.7 [M＋Na] (100).
Anal. calcd for C18H11BrF2N2O3: C 51.33, H 2.63, N
6.65; found C 51.32, H 2.61, N 6.81.
－
1
1490, 1460, 1280, 1140, 1090, 1010 cm ; MS/ESI m/z
(%): 378.8 [M＋Na]＋ (100); Anal. calcd for C19H14-
F2N2O3: C 64.04, H 3.96, N 7.86; found C 64.01, H 3.99,
N 8.00.
N-(4-Methylbenzoyl)-N'-[5-(2',6'-difluorophenyl)-2-
furoyl]hydrazine (I28): Yellow powdery crystals, yield
1
68.3%, m.p. 159—160 ℃. H NMR (DMSO-d6, 300
N-Benzoyl-N'-[5-(2',4'-difluorophenyl)-2-furoyl]hyd-
razine (I23): Light yellow powdery crystals, yield
MHz) δ: 2.39 (s, 3H, CH3), 7.04—7.06 (m, 1H, ArH-Fu),
7.27—7.35 (m, 4H, FuH＋ArH-Fu＋2ArH), 7.47 (d,
J＝3.66 Hz, 1H, FuH), 7.52—7.59 (m, 1H, ArH-Fu),
7.83—7.85 (m, 2H, ArH), 10.45 (s, 1H, NH), 10.46 (s,
1H, NH); IR (KBr) ν: 3200, 2900, 1630, 1520, 1490,
1
64.3%, m.p. 145—146 ℃. H NMR (DMSO-d6, 300
MHz) δ: 6.99 (t, J＝3.75 Hz, 1H, FuH), 7.32—7.38 (m,
2H, ArH-Fu＋FuH), 7.44—7.62 (m, 4H, ArH-Fu＋
3ArH), 7.92—7.95 (m, 2H, ArH), 8.24—8.33 (m, 1H,
ArH-Fu), 10.55 (s, 1H, NH), 10.66 (s, 1H, NH); IR
(KBr) ν: 3200, 2900, 1640, 1600, 1580, 1530, 1480,
－
1
1470, 1440, 1390, 1110 cm ;＋MS/ESI m/z (%): 357.1
[M＋H]＋ (3), 378.8 [M＋Na] (100). Anal. calcd for
C19H14F2N2O3: C 64.04, H 3.96, N 7.86; found C 63.89,
H 4.03, N 8.06.
－
1
1410, 1290, 1260, 1210, 1120, 1010 cm . Anal. calcd
for C18H12F2N2O3: C 63.16, H 3.53, N 8.18; found C
63.04, H 3.54, N 8.26.
N-Benzoyl-N'-[5-(2',6'-difluorophenyl)-2-furoyl]hyd-
razine (I29): Yellow powdery crystals, yield 50.6%, m.p.
159—160 ℃. 1H NMR (DMSO-d6, 300 MHz) δ:
7.04—7.06 (m, 1H, ArH-Fu), 7.28—7.33 (m, 2H, Fu＋
ArH-Fu), 7.47—7.61 (m, 5H, FuH＋ArH-Fu＋3ArH),
7.91—7.94 (m, 2H, ArH), 10.49 (s, 1H, NH), 10.52 (s,
1H, NH); IR (KBr) ν: 3200, 2900, 1630, 1520, 1460,
N-(3-Methylbenzoyl)-N'-[5-(2',4'-difluorophenyl)-2-
furoyl]hydrazine (I24): White powdery crystals, yield
1
60.5%, m.p. 193—193.5 ℃. H NMR (DMSO-d6, 300
MHz) δ: 2.40 (s, 3H, CH3), 6.99 (t, J＝3.74 Hz, 1H,
FuH), 7.32—7.52 (m, 5H, FuH＋2ArH-Fu＋2ArH),
7.71—7.76 (m, 2H, ArH), 8.25—8.33 (m, 1H, ArH-Fu),
10.50 (s, 1H, NH), 10.65 (s, 1H, NH); IR (KBr) ν: 3200,
－
＋
1
1290, 1010 cm ＋; MS/ESI m/z (%): 343.1 [M＋H] (3),
364.8 [M＋Na] (100). Anal. calcd for C18H12F2N2O3:
C 63.16, H 3.53, N 8.18; found C 62.87, H 3.60, N 8.29.
N-(3-Methylbenzoyl)-N'-[5-(2',6'-difluorophenyl)-2-
furoyl]hydrazine (I30): Light yellow powdery crystals,
－
1
1640, 1590, 1540, 1490, 1280, 1110, 1090, 1010 cm ;
MS/ESI m/z (%): 378.9 [M＋Na]＋ (100). Anal. calcd
for C19H14F2N2O3: C 64.04, H 3.96, N 7.86; found C
64.07, H 4.10, N 7.96.
1
yield 59.0%, m.p. 188—189 ℃. H NMR (DMSO-d6,
N-(4-Chlorobenzoyl)-N'-[5-(2',6'-difluorophenyl)-2-
furoyl]hydrazine (I25): Light yellow powdery crystals,
300 MHz) δ: 2.39 (s, 3H, CH3), 7.03—7.06 (m, 1H,
ArH-Fu), 7.27—7.34 (m, 2H, FuH＋ArH-Fu), 7.41—
7.42 (m, 2H, ArH), 7.47 (d, J＝3.66 Hz, 1H, FuH),
1
yield 74.7%, m.p. 209—210 ℃. H NMR (DMSO-d6,
Chin. J. Chem. 2010, 28, 1257— 1266
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1261

Cui et al.
FULL PAPER
7.52—7.61 (m, 1H, ArH-Fu), 7.70—7.74 (m, 2H, ArH),
N-Tosyl-N'-[5-(4'-nitrophenyl)-2-furoyl]hydrazine
(II1): Light yellow powdery crystals, yield 50.0%, m.p.
244—245 ℃. 1H NMR (DMSO-d6, 300 MHz) δ: 2.38 (s,
3H, CH3), 7.29 (d, J＝3.72 Hz, 1H, FuH), 7.36 (d, J＝
8.16 Hz, 2H, ArH-S), 7.41 (d, J＝3.66 Hz, 1H, FuH),
7.73 (d, J＝8.25 Hz, 2H, ArH-S), 8.18 (d, J＝8.91 Hz,
2H, ArH-Fu), 8.31—8.34 (m, 2H, ArH-Fu), 10.07 (d,
J＝2.94 Hz, 1H, NH), 10.89 (brs, 1H, NH); IR (KBr) ν:
10.45 (s, 1H, NH), 10.47 (s, 1H, NH); IR (KBr) ν: 3200,
－
1
2900, 1630, 1590, 1510, 1470, 1290 cm ; MS/ESI m/z
(%): 357.0 [M＋H]＋ (7), 378.8 [M＋Na]＋ (100), 394.7
[M＋K]＋ (5). Anal. calcd for C19H14F2N2O3: C 64.04,
H 3.96, N 7.86; found C 63.70, H 3.98, N 7.95.
N-(4-Chlorobenzoyl)-N'-(5-phenyl-2-furoyl)hydra-
zine (I31): White powdery crystals, yield 58.1%, m.p.
－
1
1
216—217 ℃. H NMR (DMSO-d6, 300 MHz) δ: 7.18
3300, 3000, 1680, 1590, 1510, 1330, 1160 cm . Anal.
calcd for C18H15N3O6S: C 53.86, H 3.77, N 10.47; found
C 53.56, H 3.82, N 10.86.
(d, J＝3.60 Hz, 1H, FuH), 7.34 (d, J＝3.60 Hz, 1H,
FuH), 7.37—7.43 (m, 1H, ArH-Fu ), 7.47—7.53 (m, 2H,
ArH-Fu), 7.61—7.65 (m, 2H, ArH), 7.93—7.80 (m, 4H,
2ArH-Fu＋2ArH), 10.61 (s, 1H, NH), 10.63 (s, 1H,
NH); IR (KBr) ν: 3100, 1590, 1530, 1450, 1270, 1090,
N-Tosyl-N'-[5-(3'-nitrophenyl)-2-furoyl]hydrazine
(II2): Light yellow powdery crystals, yield 52.6%, m.p.
209—210 ℃. 1H NMR (DMSO-d6, 300 MHz) δ: 2.38 (s,
3H, CH3), 7.26 (d, J＝3.69 Hz, 1H, FuH), 7.34—7.38
(m, 3H, 1FuH＋2ArH), 7.72—7.79 (m, 3H, 1ArH-Fu＋
2ArH), 8.20—8.23 (m, 1H, ArH-Fu), 8.35 (d, J＝7.95
Hz, 1H, ArH-Fu), 8.76 (t, J＝1.76 Hz, 1H, ArH-Fu),
10.07 (d, J＝3.06 Hz, 1H, NH), 10.92 (brs, 1H, NH); IR
(KBr) ν: 3300, 2900, 1690, 1670, 1590, 1510, 1340,
－
1
1010 cm . Anal. calcd for C18H13ClN2O3: C 63.44, H
3.85, N 8.22; found C 63.20, H 3.87, N 8.27.
N-(4-Methoxybenzoyl)-N'-(5-phenyl-2-furoyl)hydra-
zine (I32): White powdery crystals, yield 63.9%, m.p.
185—186 ℃. 1H NMR (DMSO-d6, 300 MHz) δ: 3.84 (s,
3H, OCH3), 7.04—7.09 (m, 2H, ArH), 7.18 (d, J＝3.60
Hz, 1H, FuH), 7.33 (d, J＝3.63 Hz, 1H, FuH), 7.37—
7.42 (m, 1H, ArH-Fu ), 7.47—7.52 (m, 2H, ArH-Fu),
7.90—7.99 (m, 4H, 2ArH＋2ArH-Fu), 10.38 (s, 1H,
NH), 10.52 (s, 1H, NH); IR (KBr) ν: 3100, 2800, 1620,
1590, 1570, 1520, 1490, 1300, 1250, 1180, 1110, 1010
－
1
1160 cm . Anal. calcd for C18H15N3O6S: C 53.86, H
3.77, N 10.47; found C 53.53, H 3.76, N 10.58.
N-Isonicotinoyl-N'-[5-(4'-chlorophenyl)-2-furoyl]hy-
drazine (III1): Light yellow powdery crystals, yield
1
66.0%, m.p. 249—250 ℃. H NMR (DMSO-d6, 300
－
1
cm . Anal. calcd for C19H16N2O4: C 67.85, H 4.79, N
MHz) δ: 7.24 (d, J＝3.63 Hz, 1H, FuH), 7.35 (d, J＝
3.66 Hz, 1H, FuH), 7.58 (dd, J＝6.78, 1.92 Hz, 2H, Py),
7.83 (dd, J＝4.41, 1.65 Hz, 2H, ArH-Fu), 8.01 (dd, J＝
6.75, 1.89 Hz, 2H, Py), 8.81 (dd, J＝4.44, 1.62 Hz, 2H,
ArH-Fu), 10.79 (brs, 1H, NH), 10.80 (brs, 1H, NH); IR
8.33; found C 68.09, H 4.80, N 8.56.
N-(4-Bromobenzoyl)-N'-(5-phenyl-2-furoyl)hydra-
zine (I33): White powdery crystals, yield 69.3%, m.p.
1
203—204 ℃. H NMR (DMSO-d6, 300 MHz) δ: 7.19
－
1
(d, J＝3.60 Hz, 1H, FuH), 7.35 (d, J＝3.63 Hz, 1H,
FuH), 7.37—7.43 (m, 1H, ArH-Fu ), 7.47—7.52 (m, 2H,
ArH-Fu), 7.75—7.79 (m, 2H, ArH), 7.86—7.91 (m, 2H,
ArH), 7.97—8.00 (m, 2H, ArH-Fu), 10.62 (s, 1H, NH),
10.64 (s, 1H, NH); IR (KBr) ν: 3200, 1600, 1590, 1520,
(KBr) ν: 3200, 1590, 1540, 1480, 1450, 1280 cm ;
MS/ESI m/z (%): 363.8 [M＋Na]＋ (6), 381.1 [M＋K]＋
(15). Anal. calcd for C17H12ClN3O3: C 59.75, H 3.54, N
12.30; found C 59.75, H 3.62, N 12.21.
N-Isonicotinoyl-N'-[5-(2',4'-fluorophenyl)-2-furoyl]-
hydrazine (III2): Light yellow powdery crystals, yield
－
1
1450, 1270, 1010 cm . Anal. calcd for C18H13BrN2O3:
C 56.12, H 3.40, N 7.27; found C 55.97, H 3.56, N 7.29.
N-Benzoyl-N'-[5-(4'-methoxyphenyl)-2-furoyl]hydra-
zine (I34): Light brown powdery crystals, yield 62.8%,
1
94.3%, m.p. 231—232 ℃. H NMR (DMSO-d6, 300
MHz) δ: 7.00 (t, J＝3.71 Hz, 1H, FuH), 7.29—7.36 (m,
1H, ArH-Fu), 7.39 (d, J ＝3.63 Hz, 1H, FuH),
7.45—7.53 (m, 1H, ArH-Fu), 7.83 (dd, J＝4.44, 1.62
Hz, 2H, PyH), 8.23—8.31 (m, 1H, ArH-Fu), 8.81 (dd,
J＝4.44, 1.62 Hz, 2H, PyH), 10.78 (s, 1H, NH), 10.88 (s,
1H, NH); IR (KBr) ν: 3200, 2900, 1640, 1600, 1530,
1
m.p. 174—175 ℃. H NMR (DMSO-d6, 300 MHz) δ:
3.82 (s, 3H, OCH3), 7.01—7.07 (m, 3H, FuH＋2ArH-
Fu), 7.30 (d, J＝3.60 Hz, 1H, FuH), 7.51—7.64 (m, 3H,
ArH), 7.89—7.95 (m, 4H, 2ArH-Fu＋2ArH), 10.50 (s,
1H, NH), 10.51 (s, 1H, NH); IR (KBr) ν: 3100, 2900,
1600, 1580, 1520, 1490, 1450, 1280, 1240, 1190, 1010
－
1
1480, 128＋0, 1140, 1010 cm ; MS/ESI m/z (%): 365.9
[M＋Na] (100). Anal. calcd for C17H11F2N3O3: C
59.48, H 3.23, N 12.24; found C 59.27, H 3.33, N 12.04.
N-Isonicotinoyl-N'-[5-(2',6'-fluorophenyl)-2-furoyl]-
hydrazine (III3): Yellow powdery crystals, yield 69.2%,
－
1
cm . Anal. calcd for C19H16N2O4: C 67.85, H 4.79, N
8.33; found C 67.64, H 4.85, N 8.39.
N-(3-Methylbenzoyl)-N'-[5-(4'-methoxyphenyl)-2-fu-
royl]hydrazine (I35): White powdery crystals, yield
1
m.p. 231—232 ℃. H NMR (DMSO-d6, 300 MHz) δ:
1
65.4%, m.p. 175—176 ℃. H NMR (DMSO-d6, 300
7.05—7.06 (m, 1H, ArH-Fu), 7.27—7.35 (m, 2H, FuH
＋ArH-Fu), 7.48 (d, J＝3.63 Hz, 1H, FuH), 7.52—7.62
(m, 1H, ArH-Fu), 7.82 (d, J＝4.47, 1.56 Hz, 2H, PyH),
8.80—8.82 (m, 2H, PyH), 10.62 (s, 1H, NH), 10.85 (s,
1H, NH); IR (KBr) ν: 3200, 1670, 1620, 1590, 1510,
MHz) δ: 2.39 (s, 3H, CH3), 3.82 (s, 3H, OCH3),
7.01—7.07 (m, 3H, FuH＋2ArH-Fu), 7.30 (d, J＝3.60
Hz, 1H, FuH), 7.41—7.43 (m, 2H, ArH), 7.71—7.75 (m,
2H, ArH), 7.90—7.93 (m, 2H, ArH-Fu), 10.43 (s, 1H,
NH), 10.49 (s, 1H, NH); IR (KBr) ν: 3100, 2900, 1600,
－
1
1480, 1290, 1110 cm ; MS/ESI m/z (%): 343.9 [M＋
H]＋ (21), 365.8 [M＋Na]＋ (100). Anal. calcd for
C17H11F2N3O3: C 59.48, H 3.23, N 12.24; found C 59.40,
H 3.21, N 12.13.
－
1
1590, 1540, 1490, 1450, 1280, 1230, 1180, 1010 cm .
Anal. calcd for C20H18N2O4: C 68.56, H 5.18, N 8.00;
found C 68.42, H 5.27, N 7.97.
1262
www.cjc.wiley-vch.de
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 1257— 1266

Synthesis and Bioactivity of Novel N,N′-Diacylhydrazine Derivatives
The insecticidal activities against Culex pipiens
pallens, Aphis fabae and Tetranychus urticae
N-(2-Bromoisonicotinoyl)-N'-[5-(4'-chlorophenyl)-
2-furoyl]hydrazine (III4): Light yellow powdery crys-
tals, yield 72.9%, m.p. 226—227 ℃. 1H NMR
(DMSO-d6, 300 MHz) δ: 7.23 (d, J＝3.63 Hz, 1H, FuH),
7.35 (d, J＝3.63 Hz, 1H, FuH), 7.57 (d, J＝7.83 Hz, 2H,
ArH-Fu), 8.00 (d, J＝8.58 Hz, 2H, ArH-Fu), 8.49 (t, J＝
2.03 Hz, 1H, Py), 8.95 (d, J＝2.16 Hz, 1H, Py), 9.06 (d,
J＝1.71 Hz, 1H, PyH), 10.81 (brs, 2H, NHNH); IR
(KBr) ν: 3200, 1640, 1590, 1510, 1460, 1270, 1090,
The insecticidal activities were evaluated using pre-
viously reported procedures.21,22
Antitumor activity
All of the synthesized compounds were screened for
the preliminary in vitro anticancer activity against four
different cell lines: a human promyelocytic leukemic
cell line (HL-60), a human hepatocellular carcinoma
cell line (Bel-7402), a human gastric carcinoma cell line
(BGC-823), and a human nasopharyngeal carcinoma
cell line (KB) at the concentration of 10 µmol/L.
－
＋
1
1010 cm ; MS/ESI m/z (%): 3443.7 [M＋Na] (13).
Anal. calcd for C17H11BrClN3O3: C 48.54, H 2.64, N
9.99; found C 48.75, H 2.83, N 9.85.
N-[5-(4-Chlorophenyl)-2-furoyl]-N'-[5-(4'-chlorophe-
nyl)-2-furoyl]hydrazine (IV): White powdery crystals,
The human promyelocytic leukemic cell line (HL-
60), human hepatocellular carcinoma cell line (Bel-
7402), human gastric carcinoma cell line (BGC-823),
and human nasopharyngeal carcinoma cell line (KB)
were grown and maintained in RPMI-1640 medium
supplemented with 10% fetal bovine serum, penicillin
(100 U/mL), and streptomycin (100 µg/mL) at 37 ℃ in
humidified incubators in an atmosphere of 5% CO2. All
of experiments were performed on exponentially grow-
ing cancer cells. Numbers of viable cells of cancer were
determined by MTT33 and SRB34 assays.
1
yield 77.8%, m.p. 273—274 ℃. H NMR (DMSO-d6,
300 MHz) δ: 7.22—7.24 (m, 2H, FuH), 7.33—7.37 (m,
2H, FuH), 7.56—7.59 (m, 4H, ArH-Fu), 8.00—8.03 (m,
4H, ArH-Fu), 10.63 (s, 2H, NHNH); IR (KBr) ν: 3100,
1600, 1530, 1470, 1430, 1270＋, 1080, 1010 cm－
;
1
MS/ESI m/z (%): 462.7 [M＋Na] (24). Anal. calcd for
C22H14Cl2N2O4: C 59.88, H 3.20, N 6.35; found C 59.64,
H 3.35, N 6.52.
Biological protocols
Briefly, cancer cells (1.0×104—2.5×104 cells•
－
1
The larvicidal activity against Mythimna separata
mL ) were inoculated in 96-well culture plates (180
µL/well). After 24 h, 20 µL of the culture medium con-
taining the compounds of various concentrations were
added to the wells, and RPMI-1640 medium in control
cells, then the cells were incubated for 48 h. HL-60 cells
were assayed by MTT, and the Bel-7402, BGC-823 and
KB cells were assayed by SRB. The absorbance of each
well was measured using a microculture plate reader at
570 nm (MTT) and 540 nm (SRB). The activity is
summarized in Table 2.
The larvicidal activity of compounds I—IV was
tested against Mythimna separate (third-instar and fed
with mealie leaves) under the conditions of temperature:
(25±5) ℃, light/dark 12/12 h, and relative humidity:
(65±5)%.
The test solution was made by dissolving the com-
pounds in DMF (dimethylformamide), adding a little of
Tween-80 as the emulsifier and then diluting to a proper
volume with water. The bioassay of Mythimna separate
was operated by spray method. Percentage mortality of
Mythimna separate was observed every day and evalu-
ated 6 d after treatment.
Results and discussion
Chemistry
Evaluation is based on a percentage scale of 0—100
in which 0 means no activity and 100 means total killed.
The larvicidal activity is summarized in Table 1.
The intermediate 5-substituted phenyl-2-furoyl chlo-
Table 1 Larvicidal activity of target compounds to Mythimna separate at the concentration of 0.1%
Activity Compd. Activity Compd. Activity Compd.
10.0 I11 36.85 I21 I31
Compd.
I1
Activity
0
0
I2
95.0
75.0
90.0
95.0
10.0
45.0
65.0
0
I12
I13
I14
I15
I16
I17
I18
I19
I20
0
I22
I23
I24
I25
I26
I27
I28
I29
I30
IV
0
I32
I33
I34
I35
II1
0
I3
0
0
30.0
0
I4
19.05
50.0
0
I5
0
85.0
5.0
0
I6
0
0
I7
0
5.56
0
II2
I8
10.0
0
III1
III2
III3
III4
95.0
0
I9
4.55
4.55
75.0
I10
60.0
0
0
32.72
Chin. J. Chem. 2010, 28, 1257— 1266
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
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Cui et al.
FULL PAPER
Table 2 Anticancer activity of the target compounds at the concentration of 10 µmol/L
Inhibitory rate/%
Compd.
Calculated lg P
MTT (HL-60)
SRB (BGC-823)
SRB (Bel-7402)
SRB (KB)
I1
4.39
4.16
3.69
3.42
3.77
4.44
3.87
4.36
3.9
－
1.98
10.84
2.63
0.65
1.79
1.49
3.62
13.97
2.63
18.53
13.18
26.73
3.51
26.71
30.57
23.82
3.89
21.20
3.10
16.31
12.66
0.17
3.60
1.06
10.76
6.03
1.10
5.44
4.57
13.20
2.60
26.06
27.56
23.90
—
60.86
5.65
1.21
8.88
11.86
3.05
6.05
4.56
I2
I3
－
－
9.12
I4
－
－
1.08
3.01
5.90
2.56
I5
－
－
－
1.03
1.27
12.86
9.68
I6
－
1.46
I7
3.01
3.76
3.69
I8
－
12.81
13.15
21.01
19.36
41.16
10.65
28.12
28.12
19.64
14.97
3.69
3.25
6.88
I9
－
0.66
－
0.87
I10
I11
I12
I13
I14
I15
I16
I17
I18
I19
I20
I21
I22
I23
I24
I25
I27
I28
I29
I30
I33
I34
I35
II1
II2
III1
III2
III3
III4
IV
3.62
3.98
5.44
—
6.15
5.53
5.27
0.54
13.35
7.55
17.16
4.78
4.7
10.80
7.73
12.57
13.49
8.50
5.05
5.72
4.76
4.68
4.22
3.94
4.96
4.39
3.92
4.48
4.53
4.81
4.24
3.77
4.33
4.67
4.42
4.22
3.13
3.24
3.32
2.85
2.7
6.06
4.34
5.41
－
1.31
4.21
－
12.22
13.58
5.70
7.32
－
0.17
9.42
14.93
10.28
14.34
11.13
13.27
19.57
21.39
0.01
3.07
16.76
11.46
23.07
29.28
21.20
29.68
26.76
34.83
43.06
33.77
36.55
18.96
5.12
15.31
12.99
9.25
13.29
3.79
14.89
6.81
－
13.64
12.47
19.39
19.76
12.98
13.35
4.10
－
－
23.71
19.64
15.05
13.75
10.45
8.21
4.21
2.32
13.47
14.63
17.41
7.66
6.17
4.24
—
10.60
37.16
2.87
16.48
8.96
4.24
6.33
3.59
—
61.94
－
5.22
5.15
ride was obtained from 5-substituted phenyl-2-furoic
acid (4) which was prepared according to our previous
literatures.21,22 The target compounds were synthesized
from the reaction of 5-substituted phenyl-2-furoyl chlo-
ride with different kinds of acylhydrazines in anhydrous
dichloromethane under reflux. The synthetic route of
target compounds I—IV is shown in Scheme 1. By the
Meerwein reaction, the differently substituted anilines
were used as the starting reagents to change R2 group in
the intermediate 4 so as to get the target compounds
with diverse structures which are the basis for the fur-
ther study on their QSAR.
1264
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© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 1257— 1266

Synthesis and Bioactivity of Novel N,N′-Diacylhydrazine Derivatives
Bioactivity
activity, such as I1 and IV showed good activity to
BGC-823 with the inhibitory rates of 60.86% and
61.94% at 10 µmol/L.
Preliminary bioassays showed that some target
compounds exhibited good activity to Mythimna sepa-
rate. When the sorts and substituted positions of R2
were changed, especially when the R2 was 2-NO2, most
of the target compounds showed excellent activity to
Mythimna separate at the concentration of 0.1%, such
as compounds I2, I4 and I5 were 95.0%, 90% and
95.0%, respectively. And some of the other substituted
compounds also showed good activity to Mythimna
separate at the concentration of 0.1%, such as com-
pounds I35, III1 and IV were 75.0%, 95.0% and 85.0%
respectively. Compounds I2, I4, I5 and III1 could in-
duce the larvae premature, abnormal, and lethal larval
molt.
Two fluorine atoms were also introduced into the
target compounds in different positions. But all the
compounds containing fluorine atoms exhibited low
insecticidal activity or no activity. The introduction of
the fluorine atom onto the benzene ring decreased the
activity, which was consistent with our previous work.29
The introduction of tosyl group in the target com-
pounds was not favorable for the insecticidal activity
and anticancer activity. The introduction of isonicoti-
noyl group brought good insecticidal activity to target
compound III1, but low or no effect on anticancer ac-
tivity.
The bioactivities against Culex pipiens pallens,
Aphis fabae and Tetranychus urticae were also evalu-
ated. Unfortunately, all the target compounds exhibited
low insecticidal activity or no activity at the concentra-
tion of 0.001%, 0.05% and 0.05% respectively.
The results of anticancer activity indicated that some
compounds exhibited potential activity against the
above four human cancer cell lines. The inhibitory rates
of target compounds are summarized in Table 2, in
which I1 and IV showed good activity to BGC-823.
Their inhibitory rates were 60.86% and 61.94% respec-
tively at 10 µmol/L.
Acknowledgements
We greatly acknowledge Mr. Bi Fuchun (Nankai
University, Tianjin), Dr. Ou Xiaoming (the Hunan
Branch of National Pesticide R&D, South Center of
China) for their contribution to the insecticidal bioassay.
We expressed our gratitude to Wang Ruiqing and Prof.
Cui Jingrong (State Key Laboratory of Natural and
Biomimetic Drugs, Peking University) for their kind
help in antitumor bioassay.
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Chin. J. Chem. 2010, 28, 1257— 1266