Synthesis, insecticidal, and fungicidal screening of some new quinoline derivatives

Article abstract of DOI:10.1134/S1068162014020022

This paper describes the synthesis of a series of quinolines graphted with hydrazones, pyrazoles, pyridazine, phthalazine, triazepinone, semicarbazide, and thiomorpholide moieties and four metal complexes. These derivatives were screened against Fusarium oxysporum and the red palm weevil (RPW) Rhynchophorus ferrugineus Oliver (coleopteran: Curculionidae) as palm pathogens. Only chlorinated quinolines were active against these organisms with hydrazones being good fungicides, while those modified with pyrazoles and pyrazines showed moderate insecticidal activity. A unique trihydroxylated hydrazone was active against both organisms, while another hydrazone, the most potent fungicide in this series, exhibited insecticidal activity only upon complexation with Zn ²⁺ ions.

Full text of DOI:10.1134/S1068162014020022

ISSN 1068ꢀ1620, Russian Journal of Bioorganic Chemistry, 2014, Vol. 40, No. 2, pp. 214–227. © Pleiades Publishing, Ltd., 2014.
Synthesis, Insecticidal, and Fungicidal Screening
of Some New Quinoline Derivatives1
M. R. E. Alya, b, 2, M. M. Ibrahima, c, A. M. Okaeld, and Y. A. M. H. Gherbawye, f
a Chemistry Department, Faculty of Science, Taif University, AlhawyahꢀTaif, 888 Kingdom of Saudi Arabia
b Chemistry Department, Faculty of Applied Science, Port Said University, Port Said, 42522 Egypt
c Chemistry Department, Faculty of Science, Kafr El Sheikh University, Kafr ElꢀSheikh, 33516 Egypt
d Plant Protection Research Institute, ARC, Dokki, Cairo, Egypt
e Biology Department, Faculty of Science, Taif University, AlhawyahꢀTaif, KSA
f Botany Department, Faculty of Science, South Valley University, Qena, Egypt
Received August 13, 2013; in final form, October 7, 2013
Abstract—This paper describes the synthesis of a series of quinolines graphted with hydrazones, pyrazoles,
pyridazine, phthalazine, triazepinone, semicarbazide, and thiomorpholide moieties and four metal comꢀ
plexes. These derivatives were screened against Fusarium oxysporum and the red palm weevil (RPW) Rhynꢀ
chophorus ferrugineus Oliver (coleopteran: Curculionidae) as palm pathogens. Only chlorinated quinolines
were active against these organisms with hydrazones being good fungicides, while those modified with pyraꢀ
zoles and pyrazines showed moderate insecticidal activity. A unique trihydroxylated hydrazone was active
against both organisms, while another hydrazone, the most potent fungicide in this series, exhibited insectiꢀ
cidal activity only upon complexation with Zn2+ ions.
Keywords: quinoline, hydrazones, fungicidal, insecticidal, red palm weevil
DOI: 10.1134/S1068162014020022
2 1
INTRODUCTION
pesticides; and finally, application of biotechnology
through gene transduction to produce pest resisting
palm generations [8]. However, the progress in these
tactics is not sufficient yet to control these infections
and chemical interference is still of great demand.
Therefore, in continuation of our ongoing program to
suggest solutions to local agricultural problems in the
Middle East and worldwide as well based on synthetic
quinolines, we extended this project to the date crop
problem. In a previous work [9], a structurally diverse
Date crop damage arising from attack of date palms
Phoenix dactylifera (Palmae) by the destructive red
palm weevil (RPW) Rhynchophorus ferrugineus (Olivꢀ
ier) [1] and fungal infection with Fusarium oxysporum
[2] is a growing problem worldwide. Other palm speꢀ
cies of economic significances are also harmed by
RPW, particularly in Southern Asia. The larval stage of
RPW feeds within the trunk, which frequently reduces
the crop and finally kills the tree [3, 4]. While
F. oxysporum is treated with ordinary fungicides, for
instance, fluconazole [5], management control of
RPW is more complicated due to the concealed nature
of the larvae [1]. Chlorpyrifos 48% EC (Brand Name:
Chlorozan), an organophosphate pesticide, is a comꢀ
mon pesticide involved in RPW control [6]. These
pesticides, however, increase the production cost and
cause environmental hazards, which restricts its utilꢀ
ity, and continuous use of the ecoꢀtolerant grades lead
to the development of resistant pests [7]. Therefore,
alternatives are under investigation, including bioconꢀ
trol based on nematodes, viruses, and bacteria; inteꢀ
grated pest management (IPM) with pheromones and
quinoline series were prepared, of which compound (
I)
(Scheme 1) was quite effective against Aphids gossipy
(Glover) that harms the Egyptian cotton crop. This
derivative was contracted to be intensively investigated
in fields by Syngenta Agro S. A. E.
In the present work, special emphasis was given to
chloroquinolines having basic graphts at positionꢀ4.
This type of quinolines has special interest as chloroꢀ
quine was evolved as one of the breakthroughs in antiꢀ
malarial therapy [10]. Pharmacological potential of
the same category was also reported in anticancer
research [11, 12]. In pesticide research, the hydrazone
moiety is a highly efficient pharmacophore [7] that is
widely used in pesticide design. Hydramethylnon [13]
and metaflumizone [14] are commercial examples of
this class of pesticides (Scheme 1).
1
The article is published in the original.
Corresponding author: phone: +966 56 26 94 753; eꢀmail:
mrea34@hotmail.com.
2
214

SYNTHESIS, INSECTICIDAL, AND FUNGICIDAL SCREENING
Cl
215
N
N
F
H
N
N
N
Cl
N
OH
N
N
S
N
N
P
S
O
N
N
H
Cl
F
Fluconazole
Chlorpyrifos
(I)
H
CF3
O
N
H
N
H
H
N
N
N
N
N
OCF3
CN
H
N
N
N
Cl
F3C
CF3
Chloroquine
Hydramethylnon
Metaflumizone (Zꢀisomer)
Br
Cl
N
N
NC
H
N
Cl
N
O
N
O
R
N
S
N
H
NH2
Cl
O
CF3
Cl
Chlorantraniliprole
R = Et Ethoprole
R = CF3 Fipronil
Scheme 1. Structure of selected fungicides and pesticides.
On the other hand, phenyl pyrazoles are important based agrochemicals are known for hydroxyquinolines
only and devoted for herbicidal applications [20].
class of pesticides including
instance, ethiprole and fipronil, that effectively conꢀ
trol pests on corn and soya bean [15]. ꢀHeteꢀ
roarylpyrazoles, particularly those containing a chloꢀ
ropyridyl moiety, such as chlorantraniliprole, are
common larvicides [16]. These two classes of pestiꢀ
cides prompted us to choose the quinoline derivative
6ꢀchloroꢀ4ꢀhydraqzinoꢀ2ꢀmethylquinoline [17, 18] as
readily accessible and reliable scaffold to develop a
series of hydrazones, as well as isosteric analogues of
Nꢀaryl pyrazoles, for
N
RESULTS AND DISCUSSION
Chemistry
Substrate (III) [17, 18] was condensed with 1.1
equivalents of the relevant carbonyl compounds (IIa–k
and cinnamaldehyde in refluxing EtOH (Scheme 2
and Table 1). Generally, crystalline pure hydrazones
)
(
IVa–k) and (V) were obtained in good yields. All
N
ꢀchloropyridylpyrazoles, to be tested against both
compounds showed a recognizable molecular ion peak
corresponding to the exact mass of each derivative.
1H NMR spectra recorded in DMSOꢀd6 showed
RPW and F. oxysporum on the way to find an inteꢀ
grated solution for palm infections. Another acetylaꢀ
nilinoquinoline derivative was chosen to get a set of
thiomorpholide and semicarbazide architectures for
the same objective. It is to be mentioned that beside
the wide application of quinolines in biological, indusꢀ
broad singlet for the NHꢀproton at about
due to Hꢀbonding while the imine proton was
observed at about 8.5 ppm if not overlapped with
aromatic protons. The quinolylꢀ2ꢀmethyl protons
δ
11.0 ppm
δ
trial, and material science researches [19], quinolineꢀ could not be seen due to overlap with DMSO protons
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216
ALY et al.
at about
δ
2.5 ppm. However, its carbon could be seen in tively. The N–H stretching band was weak at about
δ
the 13C NMR as in the case of (IVb) at about 23 ppm. 3200 cm–1 and this band in the IR spectrum, as well as
In the IR spectra, all compounds showed bands at its signal at
about 1616 and 1637 cm–1 corresponding to the C=N namaldehyde suggested structure (
stretching and N–H deformation vibrations, respecꢀ Michael condensation product (VI) in this case.
δ
11.0 ppm in the 1H NMR in the case of cinꢀ
) rather than the
V
H
R2
NH2
N
N
R1
R
R3
Cl
+
O
CH3
R4
(IIa–k)
(III)
b
a
R2
R4
R1
R3
H
N
N
Ph
H
N
Ph
N
N
N
N
N
N
R
Cl
Cl
Cl
CH3
CH3
CH3
(IVa–k)
(V)
(VI)
Scheme 2. Reagents and conditions: (a) EtOH, rfx; (b) Cinnamaldehyde, EtOH, rfx.
Compound (III) was cyclocondensed with some 1,3ꢀ tate in refluxing EtOH giving rise to the pyrazole
dielectophiles like acetyl acetone and ethylacetoaceꢀ derivatives (VII) and (VIII) in good yields (Scheme 3).
Table 1. Structure and some physical data of compounds (IVa–k) and (
V)
Entry
R
R1 R2 R3
R4
Yield, %
mp,
°C
(
(
(
(
(
(
(
(
(
(
(
(
IVa
)
H
H
H
H
H
82
80
80
65
72
67
81
81
60
77
56
56
239
IVb
)
H
H
H
OMe
NO2
Cl
H
H
H
H
H
H
H
H
OH
H
–
230–2
267
IVc)
H
H
H
IVd
)
H
H
H
243–5
260
IVe
IVf
IVg
IVh
)
H
OH
H
H
H
)
H
H
OH
CH3
OMe
OH
H
230–4
256–8
242
)
H
H
H
)
H
H
OH
H
IVi
IVj
IVk
)
CH3
CH3
CH3
–
H
282
)
OH
OH
–
H
253–5
270–2
240
)
OH
–
OH
–
V)
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SYNTHESIS, INSECTICIDAL, AND FUNGICIDAL SCREENING
O
217
N
O
H
H
N
N
Cl
N
N
N
N
N
O
Cl
Cl
N
CH3
(VIII)
CH3
CH3
(VII)
(IX)
b
c
a
H
N
NH2
Cl
N
CH3
(III)
O
d
e
O
N
N
N
O
H
N
N
H
Cl
Cl
O
N
CH3
N
(X)
H
N
N
N
(XI)
Cl
N
(XII)
Scheme 3. Reagents and conditions: (a) acetylacetone, EtOH, rfx (93%); (b) ethylacetoacetate, EtOH,
rfx (51%); (c) dimethylmaleic anhydride, EtOH, rfx (71%); (d) phthalic anhydride, EtOH, rfx (86%);
(e) 2ꢀmethylbenzoxazolinꢀ4ꢀone, AcOH, rfx (74%).
In the IR of pyrazole (VII), all bands of the hydraꢀ newly formed ring structures at Cꢀ4 of the quinoline ring
zine group disappeared and smooth 1H and 13C NMR exist in two forms as seen from the 1H NMR (Figs. 1–3)
spectra were obtained. Pyrazolone (VIII) is probable due to iminolꢀketo tautomerism. In all keto forms,
to be available in solution, mostly, in the enol form due δNH
≈
9.5 ppm; H–3 of the quinoline ring is more
6.5 ppm, compared with the iminol
11.4 ppm, where δHꢀ3 5.8 ppm.
to the weakness of the C=O signal in the 13C spectrum deshielded, δHꢀ3
≈
at 173 ppm and the presence of a broad phenolic proꢀ forms, δOH
≈
≈
ton at 12 ppm in the 1H NMR spectrum, while the NH
This is interpreted by adaption of the ketoꢀform of
a perpendicular orientation at Cꢀ4 to avoid steric hinꢀ
drance between the N–H and C5–H bonds. In this
case, there is no resonance between the outꢀofꢀplane
signal was not observed. However, in solid state, as
shown in the IR spectrum, the compound is mainly
available in the keto form where a strong C=O absorpꢀ
tion band and very weak N–H stretching bands were
observed. The 13C NMR spectrum was much compliꢀ
cated, as 15 signals were observed for the 12 aromatic
carbons, presumably, due to existence of rotamers.
nitrogen atom loneꢀpair of electrons and the ꢀcloud
π
of the quinoline ring. Thus, the Hꢀ3 become
deshielded compared with the iminolꢀform which is
free of hindrance between the prementiond bonds and
the whole molecule is planar and loneꢀpair interaction
with the ꢀcloud shields the Hꢀ3 atom and comes into
resonance at higher field.
Reaction of (III) with 3,4ꢀdimethylmaleic anhyꢀ
dride, phthalic anhydride, and 2ꢀmethylbenzoxazine
is believed to proceed via cyclocondensation affording
π
pyridazinꢀ4ꢀone (IX), phthalazineꢀ1,4ꢀdione (
X), and
Further, in compounds (IX) and (X), Hꢀ3 atom in
triazipeneone (XI), respectively (Scheme 3). These the iminol form shown in (Figs. 1 and 2), the most
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218
ALY et al.
favored configuration as calculated by HyperChem afforded (XIV) in high yield, it was then incoroporated
program, is subjected to magnetic anisotropic shieldꢀ
in two different reactions. In the first one, it was conꢀ
densed with semicarbazide hydrochloride in refluxing
EtOH containing K2CO3, which was followed by
treatment with mercaptoacetic acid in refluxing
EtOH. The thiol group was just added to the intermeꢀ
diate semicarbazide (XV) without cyclyzation between
the carboxyl group and the polar head of the semicarꢀ
ing by the carbonyl group. Acquisition of the 1H NMR
at 50 C simplified the spectrum and the ketoꢀform was
°
the uniquely existing form.
1
Acquisition of the H NMR of (XI) (Fig. 3), at
C coincides with that taken at ambient temperaꢀ
50°
ture. This is quite important as it precludes the possiꢀ
bility of nucleophilic substitution and formation of bazide moiety affording (XVI) (Scheme 4). MS
(
XII). If (XII) was formed, the two D2Oꢀlabile signals showed a weak molecular ion peak at
m/z
439 and the
1H NMR was in good accordance with the formula,
however the carboxyl proton was not observed, probaꢀ
bly it was too broad to be seen. In the IR spectrum,
however, all characteristic bands of the carboxyl, as
well as amide groups, could be clearly seen, in particꢀ
ular, the O–H stretching at 2699 cm–1 and C=O
stretching at 1705 cm–1 as good evidence for the existꢀ
at low field might be correlated to partial intramolecꢀ
ular Hꢀbonding. If this is so, the Hꢀbond was to break
down at 50
To have non halogenated quinoline models for
comparison reason, compounds (XVI) and (XVII
were prepared from (XIII). Thus, nucleophilic substiꢀ
tution of chloroquinoline (XIII) [21] with ꢀaminoacꢀ
°
C and only one signal was to be seen.
)
p
etophenone in EtOH containing drops of HCl ence of the carboxyl moiety.
N
Cl
(XIII)
a
O
⋅
HCl
N
N
H
b
d
(XIV)
O
H
N
NH2
N
N
O
S
N
N
H
N
N
H
(XV)
(XVII)
c
COOH
S
H
N
NH2
N
H
O
N
N
H
(XVI)
Scheme 4. Reagents and conditions: (a) pꢀaminoacetophenone, EtOH, HCl, rfx (98%); (b) semicarbazide,
HCl, K2CO3, EtOH, rfx (80%); (c) mercaptoacetic acid, EtOH, rfx (96%); (d) S, morpholine, rfx (81%).
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SYNTHESIS, INSECTICIDAL, AND FUNGICIDAL SCREENING
219
In the second modification of (XIV), it was incorꢀ
porated in Willigrodet’s reaction with sulfur in refluxꢀ
To augment the potential of biological activity,
metal (II) complexes (XVIIIa ) and (XIX) were preꢀ
pared by treating a methanolic solution of nitrate salts
of Zn2+, Cu2+, and Ni2+ with two equivalents of the
bidentate salicylhydrazone ligand (IVe), a Schiffꢀlike
–c
ing morpholine giving rise to thiomorpholide (XVII
)
in good yield (Scheme 4). MS was in good agreement
with suggested formula and the molecular ion peak
base, in the presence of NaOH. Vanadyl complex (XIX
was prepared similarly under equimolar conditions
using VOSO4 2H2O (Scheme 5). All the complexes
)
1
was observed at
m/z
391. In the H NMR spectrum,
the four methylene entities of the morpholine moiety
were clearly seen as four triplets with the –OCH2–
protons more deshielded than the two –NCH2– entiꢀ
ties. The –C(=S)CH2– group was observed as singlet
at 4.33 ppm, while, the C=S 13C NMR signal was
observed at 199.31 ppm. The C=S IR band was
observed as strong band along with the C–N stretching
band in the range 1027–1107 cm–1, while the N–H band
was observed at 3294 cm–1, despite it was not seen in
the 1H NMR spectrum.
⋅
are colored, nonꢀhygroscopic, and thermally stable
solids indicating the strength of metalꢀligand binding.
The complexes are insoluble in water but soluble in
common organic solvents such as EtOH, DMF, and
DMSO. Electrical conductivity measurements of the
obtained complexes in EtOH recorded ΛM values of
–1
3–5
Ω
cm2 mol–1 indicating that they are neutral
and nonꢀelectrolytes [22]; elemental analyses were in
agreement with the suggested hydrated forms drawn in
(Scheme 5 and Table 2).
O
H
H
N
N
N
Cl
a
b
(IVe)
N
Cl
Cl
Cl
H2O
O
V
H2O
HN
N
O
N
H
H
O
O
O
N
V
N
S
⋅
nH2O
O
O
N
M
N
O
O
O
N
N
NH
Cl
N
(XVIIIa–c)
(XIX)
Scheme 5. Reagents and conditions: (a) MNO2 (0.5 eq), NaOH, MeOH, [M = Zn,
n
= 2.5 for (XVIIIa);
M = Cu, = 3.0 for (XVIIIb); M = Ni, = 3.0 for (XVIIIc)]; (b) VOSO4 H2O, NaOH, MeOH.
n
n
⋅
Thermal analysis of (XVIIIa) as a representative examꢀ
ple was studied using the TG–DTG technique. The
thermogram showed an endothermic event at 343 K
accompanied by a mass loss of 6.87% (Calcd. 6.14%),
assigned for removal of 2.5 water molecules of crystalꢀ
lization. The dehydration step is followed by one
decomposition process with a strong endothermic
event at 573 K due to decomposition of two mols of the
ligand, forming two mols of ZnO and ZnC2 as a final
solid.
In the electronic spectra of complexes (XVIIIa–c)
and (XIX) and their parent ligand (IVe), three very
similar absorptions in the 300–450 nm region with
maxima around 220, 365–400, and 440 nm were
observed, therefore, they are most likely to be due to
transitions involving orbitals of the ligand only.
In the IR spectra, a very strong and sharp band
located at 1578 cm–1 was assigned to the (C=N)
stretching vibration of the hydrazone moiety. This
band is shifted 27–60 cm–1 to lower wave number indiꢀ
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220
ALY et al.
11.48
O
O
O
H
O
11.36
Cl
H
N
N
9.56
O
N
N
N
N
O
H
H
N
N
6.51
O
9.81
5.75
N
N
O
H
H
Cl
H
5.86
6.72
Cl
Cl
H
N
(b)
N
(b)
Hꢀ3
Hꢀ3
9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0
(а)
11 10
9
8
7
6
5
(a)
11
10
9
8
7
6
12 11 10
1
9
8
7
6
5
1
Fig. 1. (a) H NMR of (IX) (600 MHz, DMSO, rt); (b)
Fig. 2. (a) H NMR of (
X
) (600 MHz, DMSO); (b)
1
1
H NMR of (IX) (50°C).
H NMR of (X) (600 MHz, DMSO/D O).
2
cating the coordinate bond formation, and this shift can The bands observed in the region of 477–523 cm–1
be explained by donation of electrons from nitrogen to were also assigned to (V–N) stretching, while, the
the empty
d
orbital of the metal ion [23, 24].
band at 433 cm–1 is attributed to (V–O) vibration [31].
A relatively medium broad absorption band with maxꢀ
imum at 3409–3444 cm–1 in all complexes is probably
due to the adsorbed water molecule [27]. The Raman
spectral bands, in the ligand are practically unchanged
in these complexes, however some new bands with
mediumꢀtoꢀweak intensities appeared in the region of
253 and 177 cm–1 in the complexes under study, which
are assigned to (M–O) and (M–N) vibrational modes
[25, 27]. These bands do not occur in the same posiꢀ
tion for all of the complexes, due to variation of the
metal ions.
Raman spectrum of the ligand (IVe) also showed an
intense band at 1606 cm–1, characteristic for C=N
moiety. This band shows a slight shift in zinc(II) comꢀ
plex (XVIIIa) which also indicates the coordination of
this group to the zinc(II) ion.
The presence of N–H broad band at 3282 cm–1 in
the ligand and at 3241–3291 cm–1, in the complexes
indicate that in each complex the N–H functionality
exists and is not deprotonated. In addition, the
ligand’s broad band centered at 3412 cm–1, due to the
O–H of the phenol, is probably involved in intramoꢀ
lecular hydrogen bonding [25], particularly, it disapꢀ
peared due to complexation. Shift of the C–O stretchꢀ
BIOLOGY
ing of phenol to higher wave number, 1365–1398 cm–1
,
confirms that metal ions are bound to the phenolic
oxygen. The strong bands observed at 1655–1533 cm–1
and 1093–1005 cm–1 are tentatively assigned [26, 27]
to asymmetric and symmetric stretching of (C=C) and
(C=N) of quinoline ring breathing and deformations
respectively. These bands remain practically
unchanged after complexation suggesting the nonꢀ
involvement of quinolinicꢀnitrogen in complex forꢀ
Insecticidal Activity
Only chloroquinolines modified with basic 5ꢀmemꢀ
bered and 6ꢀmembered rings showed insecticidal
activity against the eggs of RPW, with phthalazine (X)
being the most active one, but still far away from chloꢀ
razan, which gives maximum activity (93.3% mortalꢀ
ity) at 0.004 M concentration, which is fiveꢀfold less
concentrated than the test concentration of the synꢀ
thesized samples (Table 3).
mation. The oxidovanadium(IV) complex (XIV
showed a strong band in the region 943–884 cm–1
which has been assigned to (V=O) with a monomeric
)
,
The study showed the importance of the chlorine
square pyramidal coordination geometry [26–28]. atom for insecticidal activities, as compounds (XVI
)
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SYNTHESIS, INSECTICIDAL, AND FUNGICIDAL SCREENING
221
Table 2. Analytical and physical data of metal complexes (XVIIIa–c) and (XIX
)
Chemical analysis found (calc.), %
Yield,
%
Melting Molar cond.,
point
Compound
L = IVe
Empirical formula
Color
Ω
–1 cm2 mol–1
C
H
N
M
C17H14ClN3O
(311.76)
Yellow
[Zn(L)2]
(XVIIIa)
⋅
2.5H2O
3H2O
C34H33Cl2N6O4.5Zn 79 Yellow
(733.95)
>300
>300
3.24
3.34
3.12
4.41
54.82 4.65 11.20 8.78
(55.63) (4.53) (11.45) (8.90)
[Cu(L)2]
(XVIIIb)
⋅
C34H34Cl2N6O5Cu
(741.13)
83 Brown
55.82 3.82 11.97 8.69
(55.10) (4.62) (11.34) (8.57)
[Ni(L)2]
(XVIIIc)
⋅
3H2O
C34H28Cl2N6O2
(736.30)
81 Yellowish >300
brown
54.50 4.36 18.80 7.84
(55.46) (4.65) (11.41) (7.97)
[VO(L)(H2O)]2ꢀ(SO4) C34H30Cl2N6O10SV2 77 Yellow
(XIX) (887.50)
>300
46.85 3.41 10.40 11.69
(46.01) (3.72) (9.47) (12.48)
and (XVII) were inactive. Interestingly, polyhydroxyꢀ
hydrazone (IVk) was the unique derivative that showed
fungicidal and insecticidal activities which might be an
axis for developing a complete solution for palm proꢀ
tection. Nevertheless, (IVe) was inactive, only its zinc
EXPERIMENTAL
Chemistry
Melting points were determined on Gallenkamp
apparatus and are uncorrected. Flash chromatography
was carried out on silica gel (Baker, 30–60 μm). TLC
complex (XVIIIa) could show the same activity as (
X).
monitoring tests were carried out using plastic sheets
precoated with silica gel 60 F245 (layer thickness
0.2 mm) purchased from Merck. Spots were visualized
Phthalazine ( ) and the zinc complex (XVIIIa
X
)
showed the highest toxicities among the synthesized
compounds (25% of the control), they have the lowest
slope value of 1.5 (22% of the control). Consequently,
the test organism individuals have the least homogeneꢀ
ity in their sensitivity and/or resistance to these derivꢀ
atives compared with, for instance, pyrazole (VII),
which is less toxic (20% of the control) but has the
highest slope value of 3.4 (50% of the control).
by their fluorescence under UVꢀlamp (
λ
245 and
366 nm) or staining with iodine vapour. NMR spectra
were recorded on an AC200 Brucker instrument of the
Technical University in Vienna, a Varian Mercury VXꢀ300
instrument at Cairo University, and Bruker 600 MHz
spectrometer, Central laboratory, King Abd El Aziz,
Fungicidal Activity
O
O
10.27
Screening of the newly synthesized quinoline
derivatives at unique concentration of 0.02 M in
DMSO revealed activity for nearly all the hydrazones.
Fluconazole was used as internal standard, i.e. positive
control, under the same conditions and DMSO was
used as negative control (Table 4).
N
N
11.54
Cl
H
N
N
N
N
H
N
N
90
5.47
H
Cl
H
6.36
Inspection of the inhibition zones showed that
hydrazone (IVe) with ortho OHꢀgroup, which is effiꢀ
cient metal ion chelator, and its analogue (IVi) are the
most active derivatives giving reason for these derivaꢀ
tives to be investigated more for potential application
as fungicides for palm protection. Other derivatives,
including p electron withdrawing (IVc) or even donatꢀ
ing groups (IVg), gave activity comparable to fluconaꢀ
zole, therefore, they are also promising for further
investigation as candidates for palm protection. None
of the heterocyclic graphted quinolines, nonhalogeꢀ
nated derivatives, or metal complexes could show any
fungicidal activity.
12
11
10
9
8
7
6
5
1
Fig. 3. H NMR of (XI) (600 MHz, DMSO).
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 40
No. 2 2014

222
ALY et al.
Table 3. Toxicity results of active derivatives against red palm weevil (RPW) Rhynchophorus ferrugineus Oliver
Compd.
LC25
LC50
LC90
Slope
Toxicity index (%)
13.085
(
(
(
(
(
(
IVk
)
0.420 0.387
0.455
0.726 0.657
0.822
2.047 1.641
2.762
2.846 0.231
VII
)
0.294 0.272
0.316
0.460 0.428
0.499
1.075 0.921
1.318
3.476 0.264
3.241 0.268
1.549 0.123
3.386 0.229
1.549 0.123
6.987 0.401
20.652
15.860
25.469
16.814
25.469
100.000
IX)
0.371 0.342
0.399
0.599 0.551
0.664
1.489 1.235
1.921
X)
0.137
– –
0.373
– –
2.505
– –
XI
)
0.357 0.331
0.383
0.565 0.527
1.018
1.351 1.168
1.628
XVIIIa
)
0.137
– –
0.373
– –
2.505
– –
Chlorozan
0.076
– –
0.095
– –
0.145
– –
Jeddah, Saudi Arabia. IR spectra were recorded using measurements were carried out using Equiptronics
digital conductivity meter model JENWAY 4070 at
a JASCO FT IRꢀ460 plus spectrometer while the mass
spectra were recorded on a GCMSꢀQP 1000Ex Shiꢀ
madzu spectrometers in the microanalysis unit at
Cairo University and ATRꢀAlpha FTꢀIR Spectrophoꢀ
tometer from 400 to 4000 cm–1. Raman spectra were
obtained as powders in glass capillaries on a Nicolet
FT Raman 950 spectrophotometer. The spectra were
recorded at room temperature with a germanium
detector maintained at liquid nitrogen temperature
and using 1064 nm radiation generated by NdꢀYAG
laser with a resolution of 2 cm–1. The conductivity
room temperature for
1
×
10–3 mol L–1 solutions. All
UVꢀVis measurements were recorded by Perkinꢀ
Elmer Lambda 25 UV/Vis doubleꢀbeam spectrophoꢀ
tometer. Thermal analyses of the complexes were
recorded on a Netzsch STA 449F3 with system interꢀ
face device in nitrogen. The temperature scale of the
instrument was calibrated with highꢀpurity calcium
oxalate. The operational range of the instrument was
from ambient to 1200
for dynamic TG scans at 10
°
C
. Pure sample (5 mg) was used
°
C min–1. Insecticidal
activities were evaluated at the Insect Research Instiꢀ
tute, Cairo Egypt, while the fungicidal activities were
estimated at the Biology Department, Taif University,
Taif, Saudi Arabia.
Table 4. Fungicidal (F. oxysporum) activities
Fungicidal activity
Entry
General Procedure for the Synthesis of Hydrazones
inhibition zone diameter, mm* MIC, mM
(
IVa
A mixture of compound (III) (1 mmol) and the
appropriate carbonyl derivative (IIa ) or cinnamalꢀ
–k and V)
(
(
(
(
(
(
(
(
(
(
(
(
IVa
)
14
15
17
14
24
15
17
12
20
12
16
15
32
1.48
1.40
0.88
1.48
0.77
1.48
0.89
1.48
0.84
1.80
1.10
1.40
0.45
IVb
)
–k
dehyde (1.1 mmol) in EtOH (5 mL) was refluxed on a
boiling water bath for 2 h and then left to reach ambiꢀ
ent temperature. The crystalline product that sepaꢀ
rated was filtered at the pump, washed thoroughly with
Et2O–petroleum ether (1 : 1) mixture, and dried well
to afford analytically pure product.
IVc
)
IVd
)
IVe
IVf
IVg
IVh
)
)
)
(E)ꢀ4ꢀ(2ꢀBenzylidenehydrazinyl)ꢀ6ꢀchloroꢀ2ꢀmeꢀ
)
thylquinoline (IVa). Yellow crystals; IR (νmax, cm–1):
1574 (C=Nstr), 1650 (N–Hdef), 3203 (N–Hstr).
Found, %: C 69.06, H 4.73, N 13.6. C17H14ClN3
(295.77). Calcd., %: C 69.04; H 4.77; N 14.21.
IVi
IVj
IVk
)
)
)
V)
1H NMR (200 MHz, DMSOꢀ
d
6):
NH), 7.10–8.35 (10 H, m, 9 Ar, –CH=N–), 2.49
(3 H, s, CH3). 13C NMR (50 MHz, DMSO):
160.26
(C=Nquinoline), 134.84, 129.48, 129.28, 128.74, 127.98,
δ
11.10 (1 H, bs,
Fluconazole**
δ
* Measurements at 0.02 M (200
** Reference fungicide.
µ
L).
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 40
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2014

SYNTHESIS, INSECTICIDAL, AND FUNGICIDAL SCREENING
223
126.63, 120.78 (15C), 24.80 (CH3). EIꢀMS
295 (M, 21), 192 (37), 176 (11), 122 (30), 105 (49), 77
(65), 51 (100).
m
/
z
(%):
(
E
)ꢀ4ꢀ((2ꢀ(6ꢀChloroꢀ2ꢀmethylquinolinꢀ4ꢀyl)hyꢀ
drazono)methyl)phenol (IVf). Yellow crystals; IR
νmax, cm–1): 1588 (C=Nstr), 3469 (O–Hstr). Found, %:
(
C 63.81, H 4.64, N 12.82.65 (80). C17H14ClN3O.
0.5 H2O (320.80). Calcd., %: C 63.64; H 4.72;
(
E
)ꢀ6ꢀChloroꢀ4ꢀ(2ꢀmethoxybenzylidene)hydraziꢀ
nyl)ꢀ2ꢀmethylquinoline (IVb). Yellow crystals; IR
νmax, cm–1): 1583 (C=Nstr), 3206 (N–Hstr). Found, %:
N 13.10. (1H NMR, DMSOꢀ
d6):
δ
10.75 (1 H, br.s,
(
NH), 9.79 (1 H, br.s, OH), 8.10 (2 H, m, Hꢀ8,
CH=N), 6.95 (1 H, s, Hꢀ3quinoline), 6.63–7.39 (4 H,
m, Hꢀ7quinoline, Hꢀ5quinoline, Hꢀ3phenol, Hꢀ5phenol), 6.61
C 66.24, H 4.93, N 12.94. C18H16ClN3O (325.80).
1
Calcd., %: C 66.36, H 4.95, N 12.90. H NMR
(200 MHz, DMSOꢀ
8.45 (9 H, m, Ar, –CH=N–), 3.79 (3 H, s, –OMe), 2.56
(3 H, s, CH3) 6): 160.26
13C NMR (50 MHz, DMSOꢀ
(C=Nquinoline), 146.21, 142.91, 130.41, 129.34,
128.14, 127.33, 120.53, 114.23, 101.02 (15C, Ar),
55.20 (–OMe), 23.20 (CH3). EIꢀMS
(M, 100), 217 (15), 192 (66), 164 (40), 134 (44), 107
(27), 77 (78).
d6):
δ
10.98 (1 H, br. s, NH), 6.95–
(2 H, d,
J
7.1 Hz, Hꢀ2phenol, Hꢀ6phenol), 2.45 (3 H, s,
d
CH3). 13C NMR (50 MHz, DMSOꢀ
6): δ 158.83
;
d
δ
(C=Nquinoline), 115.64, 120.78, 125.86, 127.82, 128.36,
129.39 (15C, Ar, CH=N), 23.10 (CH3). EIꢀMS
m
/
z
(%): 311 (M, 100), 218 (21), 192 (54), 164 (46),
128 927), 93 (55).
m/z (%): 325
(E
)ꢀ6ꢀChloroꢀ2ꢀmethylꢀ4ꢀ(2ꢀ(4ꢀmethylbenzylidene)
hydrazinyl)quinoline (IVg). Creamꢀcolored plates; IR
νmax, cm–1): 1585 (C=Nstr), 3138 (N–Hstr). Found, %:
(E)ꢀ6ꢀChloroꢀ2ꢀmethylꢀ4ꢀ(2ꢀ(4ꢀnitrobenzylidene)
hydrazinyl)quinoline (IVc). Brown crystals; IR (νmax
cm–1): 1329 (NO2sym str), 1565 (NO2asym str), 1584
(C=Nstr), 3194 (N–Hstr). Found, %: C 59.21, H 3.83,
N 16.21. C17H13ClN4O2 (340.77). Calcd., %: C 59.92,
(
,
C 69.72, H 5.01, N 13.59. C18H16ClN3 (309.81). Calcd.,
%: C 69.79; H 5.21; N 13.56. 1H NMR (600 MHz, DMꢀ
SOꢀ
8.34 (2 H, m, Hꢀ8quinoline
8.4 Hz, Hꢀ7quinoline), 7.62 (2 H, d,
Hꢀ6toluene), 7.52 (1 H, d, 7.8 Hz, Hꢀ5quinoline), 7.25 (1
H, s, Hꢀ3quinoline), 7.20 (2 H, d, 7.2 Hz, Hꢀ3toluene, Hꢀ
5toluene), 2.54 (3 H, s, CH3 quinoline), 2.33 (3 H, s,
CH3toluene). EIꢀMS (%): 309 (M, 100), 294 (2.03),
281 (2.25), 274 (4.43), 256 (4.17), 246 (2.24), 232
(2.17), 218 (24).
)ꢀ5ꢀ((2ꢀ(6ꢀChloroꢀ2ꢀmethylquinolinꢀ4ꢀyl)hydraꢀ
d
6):
δ
10.90 (1 H, br.s, NHD Oexchangeable
)
, 8.28–
N=CH–), 7.73 (1 H, d,
7.2 Hz, Hꢀ2toluene
2
,
⎯
J
,
1
H 3.85, N 16.44. H NMR (200 MHz, DMSOꢀ
d6):
J
δ
11.40 (1 H, bs, NH), 7.28–8.45 (9 H, m, Ar–H,
–CH=N–), 2.56 (3 H, s, CH3). EIꢀMS (%):
340 (M, 92), 310 (10), 218 (14), 191 (57), 164 (100),
123 (33), 99 (28), 76 (62).
J
m/z
J
m/z
(E)ꢀ6ꢀChloroꢀ4ꢀ(2ꢀ(4ꢀchlorobenzylidene)hydrazinyl)ꢀ
2ꢀmethylquinoline (IVd). Yellow crystals; IR (νmax, cm–1):
1586 (C=Nstr), 1643 (N–Hdef), 3195 (N–Hstr).
Found, %: C 61.23, H 3.85, N 12.56. C17H13Cl2N3
(E
zono)methyl)ꢀ2ꢀmethoxyphenol (IVh). Faint brown
crystals; IR (νmax, cm–1): 1586 (C=Nstr), 3266 (N–
Hstr), 3451(O–Hstr).Found, %: C 62.95, H 4.36, N 11.86.
1
(330.21). Calcd., %: C 61.83, H 3.97, N 12.73. H
NMR (200 MHz, DMSOꢀ
7.20–8.70 (9 H, m, Ar, –N=CH–), 2.50 (3 H, s,
CH3). 13C NMR (50 MHz, DMSOꢀ
6): 158.83
(C=Nquinoline), 133.82, 133.57, 129.53, 128.76, 128.20,
128.02, 120.85, 101.01 (15C, Ar), 24.23 (CH3). EIꢀMS
d6):
δ
11.20 (1 H, br. s, NH),
C18H16ClN3O2 (341.79). Calcd., %: C 63.25, H 4.72,
1
d
δ
N 12.29. H NMR (600 MHz, DMSOꢀ
(1 H, s, NHD Oexchangeable
d
6):
δ
10.89
)
, 9.50 (1 H, s, OHD Oexchangeable ,
)
2
2
8.26–8.39 (2 H, m, Hꢀ8quinoline, –N=CH–), 7.61 (1 H,
s, Ar), 7.75 (1 H, s, Ar), 7.37 (1 H, s, Ar), 7.26 (1 H, s,
m
/
z
(%): 330.0 (M, 28.6), 3.29 (43), 239 (10), 218
(350, 192(53), 164 (55), 137 (39), 111 (59), 89 (100).
Hꢀ3quinoline) 6.83, 7.15 (2 H, 2d,
s, –OCH3), 2.49 (3 H, s, CH3quinoline). EIꢀMS
341 (M, 100), 325 (2), 311 (2), 298 (3), 291 (1), 270 (1).
J
7.8 Hz), 3.82 (3 H,
(E)ꢀ2ꢀ((2ꢀ(6ꢀchloroꢀ2ꢀmethylquinolinꢀ4ꢀyl)hydraꢀ
m/z
(%):
zono)methyl)phenol (IVe). Yellow crystals; IR (νmax
,
cm–1): 1600 (C=Nstr), 1641 (N–Hdef), 2921 (–C=N–⋅⋅⋅
H–O–), 3152 (N–Hstr). Found, %: C 61.57, H 5.00, N
12.51. C17H14ClN3O. H2O (329.81). Calcd., %:
(E)ꢀ4ꢀ(1ꢀ(2ꢀ(6ꢀChloroꢀ2ꢀmethylquinolinꢀ4ꢀyl)hydraꢀ
zono)ethyl)phenol (IVi). Yellow crystals; IR (νmax, cm–1):
1592 (C=Nstr), 1643 (N–Hdef), 3402 (O–Hstr).
Found, %: C 64.42, H 5.08, N 12.61. C18H16ClN3O.
0.5 H2O (334.83). Calcd., %: C 64.56, H 5.12, N 12.55%.
1
C 61.90, H 4.88, N 12.70. H NMR (200 MHz,
10.91 (1 H, bs, NH), 10.10 (1 H, br.s,
DMSOꢀ
d
6):
δ
OH), 8.09–8.52 (2 H, m, Hꢀ8quinoline, –CH=N–),
7.23–7.61 (3 H, m, Ar), 6.59–6.92 (3 H, m, Ar), 7.12 (1
1H NMR (300 MHz, DMSOꢀ
NH), 9.52 (1 H, br. s, OH), 6.78–8.23 (8 H, m, Ar),
2.41, 2.47 (6 H, 2s, 2 CH3). EIꢀMS (%): 325 (M,
63), 248 (10), 218 914), 192 (39), 164 (18), 134 (100),
91 921), 63 (60).
)ꢀ2ꢀ(1ꢀ(2ꢀ(6ꢀChloroꢀ2ꢀmethylquinolinꢀ4ꢀyl)hydraꢀ
zono)ethyl)benzeneꢀ2,6ꢀdiol (IVj). Yellow powder;
d6):
δ
10.71 (1 H, s,
13
H, m, Ar), 2.45 (3 H, s, CH3). C NMR (50 MHz,
δ
m/z
DMSOꢀd6):
160.66 (C=Nquinoline), 136.35, 130.56,
129.11, 122.21, 119.40, 117.15, 115.94, (15C, Ar,
CH=N), 23.15 (CH3). EIꢀMS m/z (%): 311 (M, 30),
294 (21), 240 (17), 209 (18), 192 (100), 164 (64), 143
(37), 123 (49), 93 (78), 65 (90).
(E
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 40
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2014

224
ALY et al.
13
IRꢀKBr (νmax, cm–1): 1616 (C=Nstr), 1636 (N–Hdef), 2.24, 2.17 (9 H, 3s, 3 CH3). C NMR (150 MHz,
3227 (N–Hstr), 3553–3410 (O–Hstr). Found, %: CDCl3): 159.57, 150.53, 147.69, 143.30, 141.12,
C 62.65, H 4.75, N 12.10. C18H16ClN3O2. 0.25 H2O 132.78, 131.15, 130.50, 124.20, 122.57, 120.46,
116.42, 107.08 (12 Car), 25.33 (CH3quinoline), 13.64,
11.75 (2CH3 pyrazole). EIꢀMS (%): 271 (M, 11), 270
δ
(346.32). Calcd., %: C 62.42, H 4.72, N 12.10.
1H NMR (200 MHz, DMSOꢀ
6): 9.80–12.20 (3 H,
3 br.s, 2 OH, NH), 6.32–8.28 (7 H, m, Ar), 2.29–2.47
m/z
d
δ
(28), 250 (100), 229 (63), 225 (63).
13
(6 H, 2s, 2 CH3). C NMR (50 MHz, DMSOꢀ
155.55 (C=Nquinoline), 130.14, 127.73, 127.24,
107.52, 106.88 (15C, Ar, CH=N), 23.74 (CH3quinoline),
18.21 (CH3). EIꢀMS (%): 341 (M, 50), 324 (28),
192 9100), 166 (21), 150 (82), 102 (53), 77 (50).
)ꢀ4ꢀ(1ꢀ(2ꢀ(6ꢀChloroꢀ2ꢀmethylquinolinꢀ4ꢀyl)hydraꢀ
d6):
1ꢀ(6ꢀChloroꢀ2ꢀmethylquinolinꢀ2ꢀyl)ꢀ5ꢀmethylꢀ1Hꢀ
pyrazolꢀ3(2H)ꢀone (VIII). A mixture of (III) (0.24 g,
1.1 mmol) and ethylacetoacetate (3 mL) was heated
under reflux for 3 h, then left to reach ambient temperꢀ
ature. The precipitate was filtered and recrystallized
from EtOH or MeOH/AcOH to afford (VIII) (0.2 g,
δ
m/z
(E
64%) as fine colorless crystals.
7 : 3); mp 253
C. IR (νmax, cm–1): 829 (C–Clstr), 1549
Amide II), 1615–1599 (Amide I), 1747 (C=Ostr), 3101
Rf 0.3 (toluene–acetone,
zono)ethyl)benzeneꢀ2,3,4ꢀtriol (IVk). Brown powder;
IRꢀKBr (νmax, cm–1): 1615 (C=Nstr), 1637 (N–Hdef),
3232 (N–Hstr), 3562–3411 (3 OHstr). Found, %: C
57.58, H 4.60, N 11.20. C18H16ClN3O3. H2O (375.84).
°
(
(N–Hstr). Found, %: C 61.11, H 4.03%. C14H12ClN3O
1
1
(273.72). Calcd., %: C 61.43, H 4.42. H NMR
Calcd., %: C 57.51, H 4.83, N 11.20. H NMR
(600 MHz, DMSO):
d, 9.0 Hz, Hꢀ8quinoline), 8.04 (1 H, d,
Hꢀ5quinoline), 7.84 (1 H, dd, 9.0, 2.4 Hz, Hꢀ7quinoline),
δ
11.99 (1 H, br. s, O–H), 8.05 (1 H,
(200 MHz, DMSOꢀ
2.27–2.45 (6 H, 2s, 2 CH3). C NMR (50 MHz,
DMSOꢀ 6): 152.62, 152.05 (2 C=N), 132.59,
d6):
δ
6.15ꢀ8.26 (6 H, m, Ar),
J
J
2.4 Hz,
13
J
d
δ
7.75 (1 H, s, Hꢀ4pyrazole), 6.00 (1 H, s, Hꢀ3quinoline), 2.73
(3 H, s, CH3quinoline), 2.00 (3 H, s, CH3pyrazole).
13C NMR (150 MHz, DMSO):
153.47, 151.56, 147.77, 145.98, 138.86, 132.55,
131.12, 130.59, 122.63, 122.04, 118.41, 105.91, 102.00
(12 CAr), 25.31 (CH3quinoline), 19.80, 14.83
(CH3pyrazole). EIꢀMS m/z (%): 275 (M + 2, 1.5), 274
(M + 1, 4), 273 (M, 0.7), 261 (11), 241 (24), 217 (40),
77 (100).
132.14, 129.11, 127.41, 123.03, 120.73, 118.64,
112.99, 112.50, 107.60, 98.64 (14 CAr), 26.22, 18.19
(2 CH3). EIꢀMS m/z (%): 357 (M, 31), 340 (16), 192
(100), 164 (21), 140 (13), 123 (15), 99 (25), 79 (16),
63 (46).
δ
159.45, 159.15,
6ꢀChloroꢀ2ꢀmethylꢀ4ꢀ((E)ꢀ2ꢀ((E)ꢀ3ꢀphenylallyꢀ
liꢀdene)hydrazinyl)quinoline (V). Yellow crystals; IR
(
νmax, cm–1): 1586 (C=Nstr), 1626 (N–Hdef), 3152
(N–Hstr). Found, %: C 70.28, H 4.96, N 12.46.
C19H16ClN3 (321.80). Calcd., %: C 70.91, H 5.01, N
1ꢀ(6ꢀChloroꢀ2ꢀmethylquinolinꢀ4ꢀyl)ꢀ4,5ꢀdimethꢀ
ylꢀ1,2ꢀdihydropyridazineꢀ3,6ꢀdione (IX). A mixture of
III) (0.3 g, 1.4 mmol) and dimethylamaleic anhyꢀ
13.06. 1H NMR (600 MHz, DMSOꢀ
d
6):
s, NH), 8.35 (1 H, s, Ar), 8.17 (1 H, d,
(1 H, d, 9.0 Hz), 7.57 (3 H, m, Ar), 7.36 (2 H, t,
7.2, 7.8 Hz), 7.28 (1 H, t, 7.2 Hz), 7.16 (1 H, s, Ar),
7.06 (1 H, dd, 9.0, 9.6 Hz), 6.95 (1 H, d, 16.2, Olefinꢀ
ic), 2.52 (3 H, s, CH3). 13C NMR (150 MHz, DMSOꢀ
6):
δ
10.95 (1 H,
(
J
9.6 Hz), 7.75
dride (0.2 g, 1.6 mmol) in EtOH (5 mL) was heated
under reflux for 4 h and then left to reach ambient
temperature. The fine crystals formed upon cooling
were collected, washed with little MeOH, then Et2O,
and dried well, and might be recrystallized from
EtOH, if necessary, to afford (IX) (0.32 g, 71%) as fine
crystals. Rf 0.46 (toluene–MeOH, 4 : 1); mp 252–
J
J
J
J
J
d
δC 159.32 (C=N), 146.76, 145.88, 145.30, 136.59,
136.16, 130.39, 129.29, 128.71, 128.34, 128.23,
126.73, 125.69, 120.52, 116.40, 101.30 (17C), 25.16
254°
C (Dec.). IR (νmax, cm–1): 835 (C–Clstr), 1570–
(CH3). EIꢀMS
(2.7), 257 (3.7), 244 (15), 230 (4).
6ꢀChloroꢀ4ꢀ(3,5ꢀdimethylꢀ1 ꢀpyrazolꢀ1ꢀyl)ꢀ2ꢀmeꢀ
m/z (%): 321 (M, 82.5), 293 (5), 279
1595 (C=Cstr, C=Nstr), 1716 (C=Ostr), 3563 (O–Hstr).
Found, %: C 58.62, H 4.68, N 12.72. C16H14ClN3O2.
0.5 H2O (324.79). Calcd., %: C 59.16, H 4.66, N 12.94.
H
thylquinoline (VII). A mixture of (III) (0.24 g,
1.1 mmol) and acetylacetone (3 mL) was heated under
reflux for 3 h, then coevaporated with toluene in vacuo
and the residue was purified by flash chromatography
(toluene–ethylacetate, 8.5 : 1.5) to afford (VII) as colꢀ
1H NMR (600 MHz, DMSO):
HD Oexchangeable , 9.56 (0.7 H, br. s, N–HD Oexchangeable ,
δ
11.36 (0.3 H, br. s, O–
)
)
2
2
8.25 (0.7 H, s, Harom), 8.15 (0.3 H, s, Ar), 7.82 (0.7 H, s,
Ar), 7.69 (0.7 H, s, Ar), 7.58 (0.3 H, s, Ar), 7.39
(0.3 H, s, Ar), 6.51 (0.7 H, s, Hꢀ3quinolineꢀKeto), 5.75
orless sunꢀshape crystals (0.29 g, 93%).
ethylacetate, 8.5 : 1.5); mp 120
(C–Clstr), 1611 (C=Nstr). Found, %: C 66.58, H 5.06, 1.93, 1.90 (6 H, 2s, 2 CH3). EIꢀMS
N 15.79. C15H14ClN3 (271.74). Calcd., %: C 66.30, 24), 307 (23), 298 (23), 280 (46), 261 (49), 260 (49),
Rf 0.12 (toluene–
°
C. IR (νmax, cm–1): 876 (0.3 H, s, Hꢀ3quinolineꢀIminol), 2.35 (3 H, s, CH3quioline),
m/z (%): 315 (M,
H 5.19, N 15.46. 1H NMR (600 MHz, DMSO):
(1 H, d, 9.0 Hz, Hꢀ8quinoline), 7.80 (1 H, dd,
9.0 Hz, Hꢀ7quinoline), 7.59 (1 H, d, 1.8 Hz, Hꢀ5quinoline),
7.56 (1 H, s, Hꢀ4pyrazole), 6.23 (1 H, s, Hꢀ3quinoline), 2.71,
δ
8.04
2.4,
243 (64), 99 (100).
J
J
2ꢀ(6ꢀChloroꢀ2ꢀmethylquinolineꢀ4ꢀyl)ꢀ2,3ꢀdihyꢀ
drophthalazineꢀ1,4ꢀdione (X). A mixture of (III) (0.3 g,
1.4 mmol) and phthalic anhydride (0.23 g, 1.5 mmol)
J
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SYNTHESIS, INSECTICIDAL, AND FUNGICIDAL SCREENING
225
in EtOH (6 mL) was heated under reflux for 6 h and ter, then a little EtOH, and dried well to afford (XV
)
then allowed reaching ambient temperature. The preꢀ (0.43 g, 80%) as creamy crude. Rf 0.48 (toluene–ethyl
cipitate was filtered and purified by flash chromatograꢀ
phy (toluene–ethyl acetate, 1 : 1) to afford ( ) as fine
yellow solid (0.15 g, 31%). f 0.18 (toluene–ethyl acꢀ
etate, 1 : 1); mp 294 C. Found, %: C 60.55, H 3.60,
acetateꢀisoꢀPrOH, 4 : 3 : 3), mp 206–208 C. IR (νmax,
°
cm–1): 1578–1607 (C=Nstr, Amide II), 1694 (Amide I),
3200 (N–Hstr), 3428, 3469 (NH2str).
X
R
°
A mixture of (XV) (0.2 g, 0.6 mmol) and mercapꢀ
toacetic acid (0.25 mL, 3.6 mmol) in EtOH was heatꢀ
ed under reflux with stirring for 5h and then allowed
reaching ambient temperature. The precipitate
N 11.30. C18H12ClN3O2. H2O (355.78). Calcd., %:
1
C 60.76, H 3.97, N 11.81. H NMR (600 MHz,
DMSO):
δ
11.48 (0.6 H, s, O–HD Oexchangeable , 9.81
)
2
(0.4 H, s, N–HD Oexchangeable
), 8.33 (0.4 H, s, Ar), 8.23 formed was filtered at the pump and recrystallized
2
from EtOH affording (XVI) (0.24 g, 96%) as fine lemꢀ
on yellow crystals. Rf 0.18 (toluene–ethyl acetate–
isoꢀPrOH, 6 : 2 : 1), mp 153–154
C. IR (νmax, cm–1):
1370, 1392 (C–Nstr, C–Ostr), 1569, 1612 (Amide II),
1661 (Amide I), 1705 (C=Oacid), 2699 (O–Hstr), 3218–
3281 (N–Hstr), 3448–3800 (NH2str). C22H25N5O3S
(0.6 H, s, Ar), 8.02 (0.4 H, s, Ar), 7.97 (0.6 H, s, Ar),
7.82, 7.72, 7.66 (4.4 H, 3m, Ar), 7.43 (0.6 H, d,
Ar), 6.72 (0.4 H, s, Hꢀ3quinolineꢀKeto), 5.86 (0.6 H, s,
Hꢀ3quinolineꢀIminol), 2.41 (3 H, s, CH3). EIꢀMS (%):
239 (M + 2, 45), 338 (M+1, 26), 337 (M, 100), 322
(2), 310 (2.6), 292 (6.5), 279 (2).
J 8.4 Hz,
°
m/z
(439.58). 1H NMR (600 MHz, CDCl3):
N–HAniline), 9.22 (1 H, s, N1–HSemicarb.), 7.91 (2 H, d,
8.4 Hz, Ar), 7.72 (2 H, m, 8.4 Hz, Ar), 7.67 (1 H,
8.4 Hz, Ar), 7.59 (1 H, s, Hꢀ5Quinoline), 7.41 (1 H,
8.4 Hz, Ar), 6.87 (1 H, s, Hꢀ3Quinoline), 6.48 (br.s,
δ
9.41 (s, 1 H,
3ꢀ(6ꢀChloroꢀ2ꢀmethylquinolinꢀ4ꢀyl)ꢀ2ꢀmethylꢀ3
Hꢀ
benzo[ ][1,2,4]triazepinꢀ5(4 )ꢀone (XI). A mixture
e
H
J
d,
d,
J
of (III) (0.5 g, 2.4 mmol) and 2ꢀmethylbenzoxazolinꢀ
4ꢀone (0.5 g, 3.1 mmol) in AcOH (2 mL) was heated
under reflux for 6 h and then allowed reaching ambient
temperature. The reaction mixture was coevaporated
with toluene azeotrope in vacuo and the residue was reꢀ
crystallized from EtOH/AcOH to afford (XI) (0.62 g,
74%) as colorless fine crystals. Rf 0.13 (toluene–
J
J
3 H, NH2, N3Semicarb.–H), 3.65 (2 H, s, CH2), 2.53
(3 H, s, C4quinol.–CH3), 2.43 (3 H, s, C6quinol.–CH3), 2.16
(3 H, s, CH3). EIꢀMS
m/z
(%): 439.55 (M+, 0.08),
438.55 (0.08), 409.4 (0.1), 389.15 (0.13), 80.0 (100).
MeOH, 4 : 1); mp 324–325°
C. IR (νmax, cm–1): 1561–
2ꢀ[4ꢀ(4,6ꢀDimethylquinolinꢀ2ꢀylamino)phenyl]ꢀ
1603 (C=N, Amide II), 1634–1649 (Amide I), 3148
(N–Hstr). Found, %: C 64.73, H 3.95, N 15.60.
C19H15ClN4O (350.80). Calcd., %: C 65.05, H 4.31, N
1ꢀmorpholinoethanethione (XVII). A mixture of (XIV
(0.24 g, 0.8 mmol), sulfur (0.2 g, 6.2 mmol), and morꢀ
pholine (3 mL) was heated under reflux with stirring
for 10 h and then allowed to stand at ambient temperꢀ
ature overnight. The crystals were filtered and washed
thoroughly with cold EtOH and dried well affording
)
15.97. 1H NMR (600 MHz, DMSO):
O–HD Oexchangeable , 10.29 (0.25 H, s, N–HD Oexchangeable ,
δ
11.56 (0.75 H, s,
)
)
2
2
8.38 (0.25 H, s, Ar), 8.34 (0.75 H, s, Ar), 8.12 (0.25 H, d,
7.2 Hz, Ar), 8.08 (0.75 H, d, 7.8 Hz, Ar), 7.88
(0.25 H, t, 8.4, 9.6 Hz, Ar), 7.77 (0.75 H, t, 7.8,
7.2 Hz, Ar), 7.72 (0.25 H, d, 7.2 Hz, Ar), 7.67 (1 H,
d, 9.0 Hz, Ar), 7.63 (0.75 H, d, 8.4 Hz, Ar), 7.55
(0.25 H, t, 7.2 Hz, Ar), 7.45 (1.75 H, m, Ar), 6.36
(XVII) (0.16 g, 50%) as fine faint yellow crystals. The
J
J
combined mother liquor was evaporated in vacuo and
the residue was purified by flash chromatography (tolꢀ
uene–ethyl acetate, 4 : 1) affording another 0.1 g raisꢀ
ing the total yield to 81%. Rf 0.16 (toluene–ethyl aceꢀ
tate, 4 : 1); mp 254–256°
C. IR (νmax, cm–1): 1027,
1107 (C=Sstr, C–Nstr), 1602 (C=Nstr), 1636 (N–Hdef),
3294 (N–Hstr). Found, %: C 70.19, H 6.30, N 10.51.
C23H25N3OS (391.57). Calcd., %: C 70.56, H 6.44, N
J
J
J
J
J
J
(0.25 H, s, Hꢀ3quinolineꢀketo), 5.47 (0.75 H, s,
Hꢀ3quinolineꢀIminol), 2.40 (3 H, s, CH3quinoline), 2.18 (3 H,
s, CH3triazepinone). 13C NMR (150 MHz, DMSO):
δ
159.65 (C=O), 157.39 (C=Nquinoline), 154.89,
1
10.73. H NMR (600 MHz, CDCl3):
δ
7.70 (1 H, d,
8.4
J 8.4, 1.2 Hz, Ar), 7.29 (2 H,
147.69, 146.85, 137.05, 133.52, 131.42, 127.58,
126.63, 126.25, 125.71, 123.36, 121.07, 119.77, 96.26
(17C), 21.52 (CH3quinoline), 19.42 (CH3triazepinone). EIꢀMS
m/z (%): 352.1 (M + 2, 42.37), 351.15 (M + 1, 24.81),
350.10 (M, 100), 335.10 (41.73), 333.15 (32.31),
308.20 (17.66).
J 9.0 Hz, Ar), 7.58 (1 H, s, Hꢀ5quin.), 7.54 (2 H, d, J
Hz, Ar), 7.43 (1 H, dd,
d,
(4 H, 2t,
J
8.4 Hz, Ar), 6.78 (1 H, s, Hꢀ3quin.), 4.37, 3.76
J
gem 9.6, vic 4.8 Hz, –OCH2), 4.33 [2 H, s,
J
–CH2C(=S)–], 3.67, 3.46 (4 H, 2t, Jgem 9.6, Jvic
4.8 Hz, 2 –NCH2–), 2.58 (3 H, s, C4quin.–CH3), 2.49
(3 H, s, C6quin.–CH3); 13CꢀNMR (150 MHz, CDCl3):
2ꢀ[1ꢀ(2ꢀCarbamoylhydrazinyl)ꢀ1ꢀ(4ꢀ(4,6ꢀdimethꢀ
ylquinolinꢀ2ꢀylamino)phenyl)ethylthio]acetic acid (XVI).
A mixture of (XIV) (0.51 g, 1.5 mmol) and semicarꢀ
bazide hydrochloride (0.2 g, 1.8 mmol) and K2CO3
(0.5 g, 3.6 mmol) in EtOH (4 mL) was heated under
reflux with stirring for 5 h and then allowed reaching
ambient temperature. The precipitate was filtered,
then stirred with warm H2O, filtered, washed with waꢀ
δ
199.31 (C=S), 131.11, 130.65, 128.22, 123.67,
123.2, 118.35, 113.75 (Ar), 65.88, 65.74 (2 O–CH2),
50.69, 49.90 (2 N–CH2) 48.73 (–CS–CH2) 21.10
(C6–CH3), 18.49 (C4–CH3). EIꢀMS m/z (%): 391.1
(M+, 0.02), 390.2 (0.02), 389.1 (0.03), 260.6 (99.98),
259.6 (88.9), 202.1 (100).
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226
ALY et al.
General procedure for the synthesis of metal comꢀ trose agar (PDA) medium. A volume of 1.0 mL of
plexes (XVIIIa–c) and (XIX). Ligand (IVe) (0.374 g, Fusarium oxysporum spore suspension was poured in
1.2 mmol) dissolved in dry MeOH (10 mL) containꢀ Petri dish and 20 mL PDA medium was poured and
ing NaOH (48 mg, 1.2 mmol) was treated with the left till solidification. Using sterile cork porer, pores in the
nitrate salt of Zn2+, Cu2+, or Ni2+ (0.6 mmol) or
VO SO4 2H2O (1.2 mmol) and the mixture was
stirred at 65 C for 2–3 h. The resulting solid was filꢀ
tered off, washed with cold dry MeOH, then dried at
100 C. The analytical and physical data of the obꢀ
middle of each plate were made. An aliquot of 200
each test compound were pipette in each pore. The
plates were incubated at 27 for 5 days. The effective
compound showed inhibition zone around the pores.
The diameter of the inhibition zones was measured.
Fluconazole, 0.02 M, was used as positive control and
DMSO as negative control.
μL of
⋅
⋅
°
C
°
°
tained metal complexes are given in (Table 2).
For determination of the minimal inhibitory conꢀ
centration (MIC), dilutions incorporated in molten
Sabouraud agar were homogenized and poured into
90ꢀmm Petri dishes. The fungus F. oxysporum was
picked from purified culture in the form of a 5–mm
agar disc and inoculated in the center of each Petri
plate. Four replicate plates were inoculated for each
tested chemical concentration. The dishes were incuꢀ
BIOLOGY
Insecticidal Screening
Cocoons and adults of RPW were collected from
infected palm trees; adults which were collected
directly from the field and those emerged from the
cocoons were put, each 3 pairs of males and females,
in a Petri dish (15
×
1.5 cm) with 3 pieces (10 1 cm)
×
bated at 25 C receiving fluorescent light with 12 h
cycling. Mean colony diameter was measured after 3,
5, and 7 days of inoculation.
°
of sugar cane as an oviposition site and adult food; this
was repeated 30 times. The sugar cane pieces were desꢀ
iccated after two days and existing eggs were collected
carefully with a small brush; each 10 eggs were put in a
1.5 cm) lined with filter paper and a
piece (1.5 0.5 cm) of sugar cane. Thirty eggs were
Petri dish (15
×
CONCLUSIONS
×
used in 3 replicates for each treatment. A volume of
0.1 mL from each test compound (0.02 M in EtOH)
was dropped on the 10 eggs in each dish and incubated
A series of hydrazones, dipolar cyclocondensation
and nucleophilic substitution products arising from 6–
chloroꢀ4ꢀhydrazinoquinaldine (III), two nonhalogeꢀ
nated quinoline derivatives, including semicarbazides
and thiomorpholides, as well as metal complexes, were
prepared and tested as insecticides and fungicides.
at 25°C. EtOH was used as negative control, while
chlorozan in H2O was used as positive control and its
recorded activity (Table 3) represents the same volume
of 0.1 mL of 0.004 M stock as field recommended
dose. The Petri dishes were examined daily and the
hatched eggs and the number of larvae which sucꢀ
ceeded to bore in the sugar cane were recorded. For
lethal dose, slope, and toxicity estimation, the stock
solution of each compound was diluted twice to have
three concentrations of 0.02, 0.01, and 0.005 M and
each concentration was tested exactly under the same
conditions described above. Mortality data were corꢀ
rected according to the Abbott formula [32] and the
corrected mortality percentage of each compound was
statistically computed according to Finney et al. [33],
from which the corresponding concentration probit
lines (LCꢀp lines) were estimated in addition to deterꢀ
mination of 25, 50, and 90% mortalities. Slope values
of tested compounds were also estimated. In addition,
the efficiency of different compounds was measured by
comparing the tested compound with the most effective
compound by using the following equation: Toxicity
index = (LC50 of the most effective compound/LC50 of
Hydrazones were active against Fusarium oxysporum
,
while the cyclocondensation products, besides the
zinc complex, were active against the red palm weevil,
with the polyhydroxylated hydrazone (IVk) being
active against both organisms. Nonhalogenated derivꢀ
atives were inactive against both organisms. Thus,
derivative (III) might be a good lead for potential funꢀ
gicides and insecticides development by further invesꢀ
tigations.
ACKNOWLEDGMENTS
The financial support of Port Said University and
Taif University (project no. 1–432–1309) and the staꢀ
tistical analysis of insecticide activities done by
Prof. Ahmad Abd El Mageed are gratefully acknowlꢀ
edged.
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