Phytogrowth activity of 3-(3-Chlorobenzyl)-5-arylidenefuran-2(5H)-ones

Article abstract of DOI:10.1515/znb-2009-0216

Nine new 3-(3-chlorobenzyl)-5-arylidenefuran-2(5H)-ones were prepared in 20-87% yields by reaction of 3-(3-chlorobenzyl)furan-2(5H)-one with pertinent aldehydes. All compounds were fully characterized by IR and NMR spectroscopy as well as MS spectrometry. The phytotoxic properties of the synthesized lactones were evaluated as the ability to interfere with the growth of Sorghum bicolor and Cucumis sativus seedlings at 10 ppm and 100 ppm. Lactone 12, at 10 ppm, was the most active and selective, inhibiting the S. bicolor and C. sativus root growth by 70.7 % and 10.7 %, respectively. At 10 ppm, lactone 14 caused the larger effect on the inhibition (41.9 %) of C. sativus. In general, the results indicate the influence of the benzylidene ring substitution on the phytotoxic activity.

Full text of DOI:10.1515/znb-2009-0216

Phytogrowth Activity of 3-(3-Chlorobenzyl)-5-arylidenefuran-2(5H)-ones
Luiz C. A. Barbosa, Antoˆnio J. Demuner, Ce´lia R. A. Maltha, Ro´bson R. Teixeira,
Kamilla A. P. Souza, and Keylla U. Bicalho
Department of Chemistry, Federal University of Vic¸osa, Av. P. H. Rolfs, S/N – 36.570.000 – Vic¸osa
- MG, Brazil
Reprint requests to Dr. Luiz Cla´udio Almeida Barbosa. Fax: (55) 31 3899 3065. E-mail: lcab@ufv.br
Z. Naturforsch. 2009, 64b, 245 – 251; received September 4, 2008
Nine new 3-(3-chlorobenzyl)-5-arylidenefuran-2(5H)-ones were prepared in 20 – 87 % yields by
reaction of 3-(3-chlorobenzyl)furan-2(5H)-one with pertinent aldehydes. All compounds were fully
characterized by IR and NMR spectroscopy as well as MS spectrometry. The phytotoxic properties of
the synthesized lactones were evaluated as the ability to interfere with the growth of Sorghum bicolor
and Cucumis sativus seedlings at 10 ppm and 100 ppm. Lactone 12, at 10 ppm, was the most active
and selective, inhibiting the S. bicolor and C. sativus root growth by 70.7 % and 10.7 %, respectively.
At 10 ppm, lactone 14 caused the larger effect on the inhibition (41.9 %) of C. sativus. In general, the
results indicate the influence of the benzylidene ring substitution on the phytotoxic activity.
Key words: Nostoclides, Herbicides, Natural Products, Cyanobacterin, Phytotoxicity
Introduction
Over the years agrochemical companies have devel-
oped and brought to the market a myriad of chemical
agents that have assisted farmers to control a variety
of pests and diseases, including weeds [1]. Herbicide
application has become the most reliable and least ex-
pensive tool of weed control [2, 3]. However, repeated
use of the same active ingredients has led to herbicide
resistance [4, 5]. Starting from the 1960s, hundreds of
weed biotypes were reported to survive herbicide ap-
plication [6]. As a consequence, there is a constant
need for the development of new herbicides to over-
come weed resistance. Moreover, modern herbicides
should have a favorable combination of properties such
as high levels of herbicidal activity, low application
rates, crop tolerance, and low toxicity to mammals.
In the last few years, the great variety of compounds
available from nature has been explored in the search
for new agents to control weeds [7, 8]. This approach
has afforded compounds that have been used directly
as herbicides [9]. Moreover, natural products may pro-
vide novel lead compounds that may be optimized us-
ing well-established strategies [10, 11].
Fig. 1. Structures of nostoclides (1), cyanobacterin (2), and
nostoclide analogs (3, 4 and 5).
ing the nostoclides 1 as lead structures for the search
of new herbicides [17 – 19]. Originally isolated from
the culture of a symbiotic cyanobacterium, Nostoc sp.,
in Peltigera canina [25], the nostoclides are struc-
turally similar to the potent phytotoxin cyanobacterin
(2) (Fig. 1). Synthetic efforts led to the preparation
Within the frame of a long-established research,
we have been using natural products as prototypes
for the preparation of new active principles to con-
trol weeds [12 – 19], insects [20 – 22] and nema-
todes [23, 24]. In this context, we have been utiliz-
c
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L. C. A. Barbosa et al. · Phytogrowth Activity of 3-(3-Chlorobenzyl)-5-arylidenefuran-2(5H)-ones
of a variety of nostoclide analogs possessing the gen-
eral structures 3 and 4 [18, 19]. It was demonstrated
that several analogs were able to significantly inhibit
the electron flow in isolated chloroplasts from water to
K3[Fe(CN)6]. As a general trend, it was found that the
inhibitory potential of lactones of the type 4 is higher
than that of other nostoclide analogs.
A basic structure-activity relationship study per-
formed by Gleason’s group [26] with cyanobacterin
(2) showed that the halogen on the benzyl aromatic
ring and the hydroxyl group at the C-3 position are es-
sential for the phytotoxic activity associated with this
compound [27– 30]. In view of the structural similarity
between the nostoclides 1 and the cyanobacterin (2),
and also considering our interest in using the former
as lead structures for the development of novel herbi-
cides, we decided to investigate if lactone analogs of
nostoclides 1 possessing a chlorine atom attached to
the benzyl aromatic ring (Fig. 1, general structure 5)
would display phytotoxic activity. In this investigation,
we describe the synthesis and structural characteriza-
tion of a series of 3-(3-chlorobenzyl)-5-arylidenefur-
an-2(5H)-one analogs of nostoclides 1. The results of
the investigation of the phytogrowth activity of these
derivatives on Sorghum bicolor and Cucumis sativus,
at two different concentrations, are also discussed.
Results and Discussion
Compound
Arylidene group
Yield (%)
87(Z)
40(Z)
20(Z)
26(Z)
33(Z)
45(Z)
46(Z)
67(Z)
25(E)
The new 3-(3-chlorobenzyl)-5-arylidenefuran-2
(5H)-one derivatives were prepared as depicted in
Scheme 1. Treatment of furan-2-yl N,N,Nꢀ,Nꢀ-tetraeth-
yldiamidophosphate (7), a compound readily available
11
12
13
14
benzylidene
1,3-dioxalenebenzylidene
4-fluorobenzylidene
4-bromobenzylidene
2-bromobenzylidene
4-trifluoromethylbenzylidene
2,5-dimethoxybenzylidene
3-nitrobenzylidene
from lactone 6 [20] with n-butyllithium promoted 15
16
a regioselective lithiation at the C-3 position of the
furan ring. The in situ generated organolithium reagent
17
18
was captured with 3-chlorobenzyl bromide affording
compound 8 which was not isolated. The alkylated
product was treated with formic acid yielding lactone 9
in 50 % overall yield (from compound 7). In the next
step, substance 9 was converted to a variety of adducts
(general structure 10) via reaction with different
aldehydes in the presence of diisopropylethylamine
(DIPEA) and tert-butyldimethylsilyltrifluorometh-
anesulfonate (TBDMSOTf). The adducts were not
isolated, and the elimination of the TBDMSO group
from them was achieved by addition of 8-diazabi-
cyclo[5.4.0]undec-7-ene (DBU) to the crude reaction
mixture, resulting in the formation of the nostoclide
derivatives 11 – 19 in yields ranging from 20 % to 87 %
(Scheme 1).
19
2,4,6-trimethoxybenzylidene
Scheme 1. Reagents and conditions: i) POCl3, ◦Et3N,
CH2Cl2, r. t.; Et2N, Et2O; ii) n-BuLi, THF, −78 C, m-
ClC6H4CH2Br; iii) HCOOH; iv) ArCHO, TBDMSOTf,
DIPEA, CH2Cl2, r. t.; v) DBU, reflux.
The structures of the synthesized derivatives were
confirmed based on IR, NMR and MS techniques.
The infrared spectra showed strong absorptions vary-
ing from 1735 to 1773 cm−1 corresponding to the C=O
stretching. The molecular ion peaks were observed in
all mass spectra confirming the molecular formulas
of the final products. The number of 13C NMR sig-
nals was consistent with the corresponding structures
of the derivatives. Two-dimensional NMR techniques
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L. C. A. Barbosa et al. · Phytogrowth Activity of 3-(3-Chlorobenzyl)-5-arylidenefuran-2(5H)-ones
247
Table 1. Effect of lactones 11 – 19 on radicle growth of S. bi-
color and C. sativus seedlings.
dent from Table 1 that the activity of the lactones varies
with the substituent of the benzylidene ring. At the
higher concentration, compound 12 was the most ef-
fective causing 75.8% inhibition while derivative 19
displayed 43.3 % inhibition.
10 ppm
%
100 ppm
Radicle %
Radicle
length (cm)a inhibition
length (cm)a inhibition
S. bicolor
54.4
The phytotoxic activity of the lactones 11 – 19 was
further investigated on Cucumis sativus, a dicotyle-
donous species (Table 1). As a general trend, the in-
hibitory effects on this species were less pronounced
compared to S. bicolor. In fact, at the higher con-
centration stimulatory effects were observed for com-
pounds 12, 17, and 19. Considering inhibitory effects
at 100 ppm, compounds 14 and 18 showed equipotent
effects being the most actives against C. sativus. On
the contrary, the fluorinated analogs 13 and 16 corre-
sponded to the less active compounds inhibiting, re-
spectively, by 17.6 % and 16.1 % at 100 ppm. It is
worth to mention the variability in plant susceptibility,
as observed for compounds 11 – 19 during the biolog-
ical evaluation on S. bicolor and C. sativus, which is a
promising feature toward the development of new se-
lective herbicides.
11
12
13
14
15
16
17
18
19
5.19c
3.33d
6.95b
5.38c
6.20b
5.67c
7.12b
6.34b
6.70b
5.25b
2.75d
4.83c
5.07c
6.11b
5.50b
4.90c
6.01b
6.45b
11.38a
25.75
53.9
75.8
57.4
55.4
46.3
51.6
56.9
47.2
43.3
–
70.7
38.9
52.7
45.5
50.2
37.4
44.3
41.1
–
Control 11.38a
CV (%) 24.03
C. sativus
11
12
13
14
15
16
17
18
19
4.81cd
5.99b
5.56c
3.90d
5.79c
5.54c
6.58b
6.99b
8.88a
28.3
10.7
17.1
41.9
13.7
17.4
1.9
−4.2
−32.3
–
4.78b
7.38ab
5.53b
3.95c
4.56c
5.63b
7.46ab
4.14c
9.20a
6.71b
19.04
28.7
−9.9
17.6
41.1
32.0
16.1
−11.2
38.3
−37.1
–
Control 6.71b
CV (%) 12.11
Experimental Section
General procedures
a Means in the same column with the same letter are not significantly
different at P = 0.05 % by Tukey’s test.
All reactions were carried out under a protective at-
mosphere of dry nitrogen or dry conditions utilizing
a calcium chloride tube adapted to the reaction flasks.
Dichloromethane, tetrahydrofuran (THF), diethyl ether, and
amines were purified as described in the literature [32]. Com-
mercially available tert-butyldimethylsilyltrifluoromethane-
sulfonate (TBDMSOTf), diisopropylethylamine (DIPEA), 8-
diazabicyclo[5.4.0]undec-7-ene (DBU), phosphoryl chloride
(POCl3), 3-chlorobenzylbromide, and aldehydes were pur-
chased from Aldrich (Milwaukee, WI, USA) and utilized
without further purification. Lactone 6 was synthesized in
(HMBC and HSQC) assisted in the 1H and 13C NMR
assignments.
Under the reaction conditions specified in Scheme 1,
it was found that the elimination of the tert-butyldi-
methylsilyloxy group (TBDMSO) of 10 led to the for-
mation of the corresponding Z isomers except for com-
pound 19 from which the E stereochemistry was ob-
tained. In the case of the Z stereoisomers, the geom-
etry of the double bound was confirmed by the ob-
served correlation between the H-4 and H-6 signals in 43 % yield from furfural employing a published method-
ology [33]. Commercially available n-butyllithium hexane
solutions (1.4 mol L−1) were titrated prior to use [34].
The 1H and 13C NMR spectra were recorded on a Var-
ian Mercury 300 instrument at 300 and 75 MHz using
CDCl3 as solvent and TMS as internal standard. Mass
spectra were recorded on a Shimadzu GCMS-QP5050A
instrument by direct insertion, in EI mode (70 eV). In-
frared spectra were recorded on a Perkin Elmer Paragon
1000 FTIR spectrophotometer, using potassium bromide
the NOESY contour plots. On the other hand, the ab-
sence of such correlation in the contour plot of com-
pound 19 accounted for the E stereochemistry of the
exocyclic double bond. The rational for these stereo-
chemical outcomes has been discussed recently in the
literature [31].
The effects of compounds 11 – 19 on radicle growth
of the monocotyledonous test species S. bicolor are
summarized in Table 1.
(1 % w/w) disks, scanning from 635 to 4000 cm−1
.
All compounds caused a significant inhibitory ef-
fect on the radicle growth of S. bicolor. None of the
compounds exerted a significant effect on the germi-
Melting points are uncorrected and were obtained from
an MQAPF-301 melting point apparatus (Microquimica,
Brazil). Analytical thin layer chromatography analyses were
nation rate. From a qualitative point of view, it is evi- conducted on aluminum-packed precoated silica gel plates.
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L. C. A. Barbosa et al. · Phytogrowth Activity of 3-(3-Chlorobenzyl)-5-arylidenefuran-2(5H)-ones
Column chromatography was performed over silica gel (60 – (3.0 mL) was placed in a 25 mL two-necked round-bottom
230 mesh).
flask, and the system was kept under nitrogen atmosphere
at r. t. To this solution, tert-butyldimethylsilyltrifluorometh-
anesulfonate (TBDMSOTf, 0.17 mL; 0.74 mmol) and di-
isopropylethylamine (DIPEA, 0.31 mL; 1.2 mmol) were
added. The resulting reaction mixture was stirred at r. t.
for 1 h, and then 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU,
0.12 mL; 1.22 mmol) was added, followed by a 3 h re-
flux. The reaction mixture was diluted with dichoromethane
Synthesis
3-(3-Chlorobenzyl)furan-2-5(H)-one (9)
A 25 mL two-necked round-bottom flask was charged
under nitrogen atmosphere with furan-2-yl-N,N,Nꢀ,Nꢀ-tetra-
ethyldiamidophosphate (7) (252 mg; 0.90 mmol) and anhy-
◦
drous THF (3.0 mL). The mixture was cooled to −78 C
(70 mL) and washed with hydrochloric acid (3 mol L−1
,
under continuous stirring, and n-butyllithium (0.5 mol L−1
in hexane, 2.8 mL; 1.4 mmol) was then added dropwise
over 8 min. The mixture was kept under continuous stirring
2 × 25 mL), followed by brine (2 × 25 mL). The organic
phase was dried with magnesium sulfate, filtered, and con-
centrated under reduced pressure to produce a yellow solid.
This residue was purified by silica gel column chromatogra-
phy eluted with hexane/dichloromethane (1 : 1 v/v), afford-
ing the required product as a solid in 45 % yield (152 mg;
0.45 mmol). – M. p. 179.1 – 179.8 ◦C. – IR (KBr) ν = 3098,
2900, 1735 (C=O), 1654, 1602, 1489, 1446, 1379, 1341,
1262, 1036, 936 cm−1. – 1H NMR (300 MHz, CDCl3):
δ = 3.71 (s, 2 H, 7-H), 5.82 (s, 1 H, 6-H), 5.98 (s, 2 H,
OCH2O), 6.79 (d, J = 8.1 Hz, 1 H, 5ꢀꢀ-H), 6.95 (t, J =
1.4 Hz, 1 H, 4-H), 7.10 (dd, J = 8.1, J = 1.8 Hz, 1 H,
6ꢀꢀ-H), 7.15 – 7.36 (m, 4 H, 2ꢀ-H/4ꢀ-H/5ꢀ-H/6ꢀ-H), 7.42 (d,
J = 1.8 Hz, 1 H, 2ꢀꢀ-H). – 13C NMR (75 MHz, CDCl3):
δ = 31.22 (C-7), 101.47 (OCH2O), 108.54 (C-5ꢀꢀ), 109.90
(C-2ꢀꢀ), 113.16 (C-6), 125.86 (C-6ꢀꢀ), 127.10 (C-4ꢀ), 127.14
(C-6ꢀ), 127.31 (C-1ꢀꢀ), 128.92 (C-2ꢀ), 130.06 (C-5ꢀ), 130.44
(C-3), 134.53 (C-3ꢀ), 139.25 (C-1ꢀ), 139.82 (C-4), 145.98
(C-5), 148.22 (C-3ꢀꢀ), 148.48 (C-4ꢀꢀ), 170.21 (C-2). – MS (EI,
70 eV): m/z (%) = 340 (100) [M]+ (C19H13ClO4), 341 (20)
[M+1]+, 342 (33) [M+2]+, 247 (6), 219 (6), 162 (40), 134
(42), 115 (20), 104 (23), 76 (70). – Anal.: calcd. C 66.97,
Cl 10.40, H 3.85; found C 67.95, Cl 10.49, H 3.90.
◦
at −78 C for 30 min, 3-chloro benzyl bromide (0.2 mL,
1.68 mmol) dissolved in anhydrous THF (3.0 mL) was then
added dropwise over 8 min, and stirring was continued at
◦
−78 C for 30 min. The reaction mixture was allowed to
warm up to r. t. under continuous stirring. Water (5.0 mL)
and ethyl acetate (20 mL) were added, the phases were sep-
arated, and the aqueous layer was extracted with ethyl ac-
etate (2 × 20 mL). The organic extracts were combined,
washed with brine (10 mL), dried (magnesium sulfate), fil-
tered, and concentrated under reduced pressure. To the re-
sulting oily residue, formic acid (1.0 mL) was added. The
resulting mixture was stirred at r. t. for 45 min, benzene
(3.0 mL) was then added, and the excess of formic acid was
removed under reduced pressure. To the residue, ethyl acetate
(10 mL) and a sodium chloride-sodium carbonate saturated
aqueous solution (3.0 mL) were added. The organic phase
was washed twice with the latter solution (2 × 10 mL). The
combined aqueous phases were extracted with ethyl acetate
(2 × 10 mL). The combined organic phases were dried over
magnesium sulfate, filtered, and concentrated under reduced
pressure. The resulting oil was purified by silica gel column
chromatography (hexane/diethyl ether 2 : 1 v/v), and the lac-
tone 9 was obtained in 50 % yield (440 mg; 2.53 mmol). – IR
(KBr) ν = 3085, 2930, 2869, 1752 (C=O), 1654, 1598, 1574,
1475, 1447, 1069, 831, 626 cm−1. – 1H NMR (300 MHz,
CDCl3): δ = 3.60 (dd, J = 3.6, J = 2.1 Hz, 2 H, 6-H), 4.60
(dd, J = 2.1, J = 3.6 Hz, 2 H, 5-H), 6.95 (quint, J = 3.6,
J = 3.6 Hz, 1 H, 4-H), 7.10 – 7.15 (m, 1 H, 6ꢀ-H), 7.20 – 7.30
(m, 3 H, 2ꢀ-H /5ꢀ-H /4ꢀ-H). – 13C NMR (75 MHz, CDCl3):
δ = 31.70 (C-6), 70.53 (C-5), 127.34 (C-6ꢀ), 127.40 (C-4ꢀ),
129.20 (C-2ꢀ), 130.30 (C-5ꢀ), 133.80 (C-3ꢀ), 134.72 (C-3),
139.52 (C-1ꢀ), 146.15 (C-4), 173.93 (C-2). – MS (EI, 70 eV):
m/z (%) = 208 (13) [M]+ (C11H9ClO2), 210 (4) [M+2]+,
173 (30), 129 (100), 128 (82), 127 (69), 115 (47), 89 (18). –
Anal.: calcd. C 63.32, Cl 16.99, H 4.35; found C 63.18,
Cl 16.71, H 4.22.
Compounds 11, 13 – 19 were prepared employing a pro-
cedure similar to that described for compound 12, and yields
are presented in Scheme 1. Structures of lactones 11, 13 – 19
are supported by the following spectroscopic data:
(5Z)-3-(3-Chlorobenzyl)-5-benzylidenefuran-2(5H)-one (11)
M. p. 128.1 – 128.8 ◦C. – IR (KBr) ν = 3060, 3024, 2922,
1762 (C=O), 1647, 1606, 1495, 1451, 1426, 1022, 937,
870 cm−1. – 1H NMR (300 MHz, CDCl3): δ = 3.67 (s, 1 H,
7-H), 5.90 (s, 1 H, 6-H), 6.94 (t, J = 1.2 Hz, 1 H, 4-H), 7.24 –
7.36 (m, 4 H, 2ꢀ-H/4ꢀ-H/5ꢀ-H/6ꢀ-H), 7.33 (t, J = 7.8 Hz, 1 H,
4ꢀꢀ-H), 7.49 (d, J = 7.8 Hz, 2 H, 2ꢀꢀ-H/6ꢀꢀ-H), 7.97 (t, J =
7.8 Hz, 2 H, 3ꢀꢀ-H/5ꢀꢀ-H). – 13C NMR (75 MHz, CDCl3):
δ = 32.17 (C-7), 109.83 (C-6), 126.97 (C-4ꢀ), 127.27 (C-6ꢀ),
128.85 (C-3ꢀꢀ/C-5ꢀꢀ), 129.87 (C-4ꢀꢀ), 130.05 (C-2ꢀꢀ/C-6ꢀꢀ),
133.00 (C-2ꢀ), 134.03 (C-5ꢀ), 133.04 (C-1ꢀꢀ), 134.54 (C-3ꢀ),
139.19 (C-1ꢀ), 139.95 (C-4), 147.47 (C-5), 170.30 (C-2). –
MS (EI 70 eV): m/z (%) = 296 (42) [M]+ (C18H13ClO2), 298
(5Z)-3-(3-Chlorobenzyl)-5-(1,3-dioxalenebenzylidene)
furan-2(5H)-one (12)
A solution of compound 9 (208 mg; 1.0 mmol) and piper- (14) [M+2]+, 268 (3), 261 (20), 243 (16), 217 (46), 216 (17),
onal (180 mg; 1.2 mmol) in anhydrous dichloromethane 215 (24), 206 (24), 202 (15), 125 (21), 124 (12), 115 (55),
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249
101 (18), 91 (17), 90 (100), 77 (11), 63 (25), 51 (20). – Anal.: 7.8, J = 1.8, J = 0.6 Hz, 1 H, 3ꢀꢀ-H), 7.50 (dt, J = 7.8, J =
calcd. C 72.85, Cl 11.95, H 4.42; found C 72.77, Cl 11.89, 1.8 Hz, 1 H, 5ꢀꢀ-H), 7.73 (dd, J = 7.8, J = 1.5 Hz, 1 H,
H 4.15.
6ꢀꢀ-H), 8.33 (dd, J = 7.8, J = 1.5 Hz, 1 H, 4ꢀꢀ-H). – 13C NMR
(75 MHz, CDCl3): δ = 31.52 (C-7), 113.26 (C-6), 119.23
(C-2ꢀꢀ), 124.86 (C-4ꢀ), 127.10 (C-6ꢀ), 127.31 (C-5ꢀꢀ), 128.94
(C-6ꢀꢀ), 129.74 (C-2ꢀ), 130.06 (C-5ꢀ), 130.44 (C-4ꢀꢀ), 131.47
(C-3ꢀꢀ), 132.23 (C-3), 134.43 (C-3ꢀ), 138.25 (C-1ꢀ), 139.83
(C-4), 146.02 (C-5), 173.21 (C-2). – MS (EI 70 eV): m/z
(%) = 374 (29) [M]+ (C18H12BrClO2), 376 (28) [M+2]+,
378 (16) [M+4]+, 295 (3), 277 (4), 260 (5), 232 (10), 215
(24), 203 (11), 196 (2), 149 (4), 115 (32), 101 (17), 89 (100),
63 (27), 39 (13). – Anal.: calcd. C 57.55, Br 21.27, Cl 9.44,
H 3.22; found C 56.99, Br 21.42, Cl 9.72, H 3.11.
(5Z)-3-(3-Chlorobenzyl)-5-(4-fluorobenzylidene)furan-
2(5H)-one (13)
M. p. 135.7 – 136.3 ◦C. – IR (KBr) ν = 3069, 2953, 2928,
2886, 2856, 1746 (C=O), 1595, 1507, 1485, 1237, 1044,
822, 800 cm−1. – 1H NMR (300 MHz, CDCl3): δ = 3.56
(s, 2 H, 7-H), 5.76 (s, 1 H, 6-H), 6.93 (t, J = 1.3 Hz,
1 H, 4-H), 7.06 (dd, Jortho = 8.7, JorthoF = 8.5 Hz, 2 H,
3ꢀꢀ-H/5ꢀꢀ-H), 7.25 – 7.38 (m, 4 H, 2ꢀ-H/6ꢀ-H/5ꢀ-H/4ꢀ-H), 7.72
(dd, Jortho = 8.7, JorthoF = 5.7 Hz, 2 H, 2ꢀꢀ-H/6ꢀꢀ-H). –
13C NMR (75 MHz, CDCl3): δ = 31.27 (C-7), 113.21 (C-6),
(5Z)-3-(3-Chlorobenzyl)-5-(4-trifluoromethylbenzylidene)
furan-2(5H)-one (16)
115.36 (d, JC−F = 21.7 Hz, C-3ꢀꢀ/C-5ꢀꢀ), 127.25 (C-4ꢀ),
2
128.87 (C-6ꢀ), 129.03 (C-2ꢀ), 129.27 (C-5ꢀ), 129.61 (C-3),
M. p. 109.2 – 109.6 ◦C. – IR (KBr) ν = 3090, 3064,
132,47 (d, JC−F = 8.6 Hz; C-2ꢀꢀ/C-6ꢀꢀ), 132.70 (C-3ꢀ),
3
136.25 (C-1ꢀ), 139.69 (C-4), 147.24 (C-5), 163.37 (1JC−F
=
2929, 2854, 1773 (C=O), 1652, 1617, 1598, 1574, 1475,
1
1324, 1167, 1124, 1068, 1016, 940, 865 cm−1. – H NMR
250 Hz, C-4ꢀꢀ), 170.12 (C-2). – MS (EI 70 eV): m/z (%) = 314
(100) [M]+ (C18H12ClFO2), 316 (33) [M+2]+, 296 (4), 279
(20), 261 (26), 215 (24), 206 (22), 183 (10), 125 (10), 136
(30), 115 (50), 108 (60), 91 (43), 89 (30), 77 (56), 51 (29). –
Anal.: calcd. C 68.69, Cl 11.26, H 3.84; found C 67.97,
Cl 11.32, H 3.77.
(300 MHz, CDCl3): δ = 3.72 (s, 2 H, 7-H), 5.93 (s, 1 H, 6-H),
7.02 (t, J = 1.3 Hz, 1 H, 4-H), 7.15 – 7.20 (m, 1 H, 6ꢀ-H),
7.25-7.35 (m, 3 H, 2ꢀ-H/4ꢀ-H/5ꢀ-H), 7.61 (d, J = 8.1 Hz,
2 H, 3ꢀꢀ-H/5ꢀꢀ-H), 7.83 (d, J = 8.1 Hz, 2 H, 2ꢀꢀ-H/6ꢀꢀ-H). –
13C NMR (75 MHz, CDCl3): δ = 31.60 (C-7), 111.34 (C-6),
122.32 (C-4ꢀꢀ), 125.86 (4ꢀꢀ-CF3), 127.40 (C-3ꢀꢀ/C-5ꢀꢀ), 127.60
(C-2ꢀ/C-6ꢀꢀ), 129.21 (C-4ꢀ), 130.27 (C-6ꢀ), 130.46 (C-2ꢀ),
130.67 (C-5ꢀ), 133.13 (C-3), 134.90 (C-3ꢀ), 136.60 (C-1ꢀꢀ),
139.01 (C-1ꢀ), 139.86 (C-4), 148.82 (C-5), 169.92 (C-2). –
MS (EI 70 eV): m/z (%) = 364 (57) [M]+ (C19H12ClF3O2),
366 (20) [M+2]+, 318 (7), 329 (8), 311 (23), 283 (28), 249
(26), 158 (56), 143 (21), 125 (11), 115 (100), 91 (20), 89
(50), 63 (39), 49 (32), 39 (29). – Anal.: calcd. C 62.57,
Cl 9.71, H 3.32; found C 62.51, Cl 9.69, H 3.24.
(5Z)-3-(3-Chlorobenzyl)-5-(4-bromobenzylidene)furan-
2(5H)-one (14)
M. p. 165.1 – 166.8 ◦C. – IR (KBr) ν = 3069, 2952, 2930,
2892, 2854, 1757 (C=O), 1643, 1577, 1487, 1405, 1311,
1279, 1144, 822, 800 cm−1. – 1H NMR (300 MHz, CDCl3):
δ = 3.72 (s, 2 H, 7-H), 5.80 (s, 1 H, 6-H), 6.94 (t, J = 1.3 Hz,
1 H, 4-H), 7.24 – 7.36 (m, 4H, 2ꢀ-H/4ꢀ-H/5ꢀ-H/6ꢀ-H), 7.48
(dd, J = 8.7, J = 1.8 Hz, 2 H, 3ꢀꢀ-H/5ꢀꢀ-H), 7.60 (d, J = 8.7 Hz,
2 H, 2ꢀꢀ-H/6ꢀꢀ-H). – 13C NMR (75 MHz, CDCl3): δ = 31.98
(C-7), 111.56 (C-6), 123.41 (C-4ꢀꢀ), 127.27 (C-4ꢀ), 128.97
(C-6ꢀ), 129.14 (C-2ꢀ), 129.18 (C-5ꢀ), 132.00 (C-2ꢀꢀ/C-6ꢀꢀ),
132.23 (C-5ꢀꢀ/C-3ꢀꢀ), 133.17 (C-3), 133.26 (C-1ꢀꢀ), 134.46
(C-3ꢀ), 137.21 (C-1ꢀ), 139.75 (C-4), 148.00 (C-5), 170.02
(C-2). – MS (EI 70 eV): m/z (%) = 374 (29) [M]+
(C18H12BrClO2), 376 (28) [M+2]+, 378 (16) [M+4]+, 295
(3), 277 (4), 260 (5), 232 (10), 215 (24), 203 (11), 196 (2),
149 (4), 115 (32), 101 (16), 89 (100), 63 (27), 39 (13). –
Anal.: calcd. C 57.55, Br 21.27, Cl 9.44, H 3.22; found
C 57.47, Br 21.36, Cl 9.50, H 3.15.
(5Z)-3-(3-Chlorobenzyl)-5-(2,5-dimethoxybenzylidene)
furan-2(5H)-one (17)
◦
M. p. 87.1 – 89.8 C. – IR (KBr) ν = 3064, 2998, 2930,
2852, 2834, 1758 (C=O), 1681, 1598, 1494, 1464, 1237,
1046, 1026, 884, 777 cm−1. – 1H NMR (300 MHz, CDCl3):
δ = 3.79 (s, 2 H, 7-H), 3.82, (s, 6 H, 2ꢀꢀ,5ꢀꢀ-OCH3), 6.43 (s,
1 H, 6-H), 6.77 (d, J = 7.6 Hz, 1 H, 3ꢀꢀ-H), 6.83 (dd, J = 7.6,
J = 2.7 Hz, 1 H, 4ꢀꢀ-H), 7.01 (t, 1 H, J = 1.2 Hz, 4-H), 7.13 –
7.17 (m, 1 H, 4ꢀ-H), 7.23 – 7.30 (m, 3 H, 2ꢀ-H/4ꢀ-H/5ꢀ-H),
7.72 (d, J = 2.7 Hz, 1 H, 6ꢀꢀ-H). – 13C NMR (75 MHz,
CDCl3): δ = 31.74 (C-7), 56.05 (2ꢀꢀ-OCH3), 56.44 (5ꢀꢀ-
OCH3), 107.15 (C-6), 111.94 (C-3ꢀꢀ), 115.90 (C-6ꢀꢀ), 116.88
(C-4ꢀꢀ), 122.76 (C-1ꢀꢀ), 127.35 (C-4ꢀ), 129.20 (C-6ꢀ), 130.29
(C-2ꢀ), 131.12 (C-5ꢀ), 134.80 (C-1ꢀꢀ), 135.80 (C-3ꢀ), 139.51
(5Z)-3-(3-Chlorobenzyl)-5-(2-bromobenzylidene)furan-
2(5H)-one (15)
M. p. 162.1 – 163.4 ◦C. – IR (KBr) ν = 3069, 2930, 2892, (C-1ꢀ), 140.47 (C-4), 147.46 (C-5), 152.40 (C-2ꢀꢀ), 153.94
1757 (C=O), 1643, 1577, 1487, 1405, 1311, 1279, 1144, 822, (C-5ꢀꢀ), 172.03 (C-2). – MS (EI 70 eV): m/z (%) = 356 (100)
800 cm−1. – 1H NMR (300 MHz, CDCl3): δ = 3.76 (s, 2 H, [M]+ (C20H17ClO4), 358 (33) [M+2]+, 321 (15), 307 (6),
7-H), 6.47 (s, 1 H, 6-H), 7.12 (s, 1 H, 4-H), 7.30 (ddd, J = 251 (14), 178 (10), 163 (40), 151 (3), 136 (40), 115 (42),
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250
L. C. A. Barbosa et al. · Phytogrowth Activity of 3-(3-Chlorobenzyl)-5-arylidenefuran-2(5H)-ones
91 (51), 77 (24), 65 (19), 51 (15). – Anal.: calcd. C 67.32, (3), 265 (4), 205 (10), 181 (31), 166 (59), 165 (21), 149 (21),
Cl 9.94, H 4.80; found C 67.13, Cl 10.03, H 4.72.
115 (37), 109 (13), 69 (20), 63 (18), 53 (13). – Anal.: calcd.
C 65.20, Cl 19.17, H 4.95; found C 65.09, Cl 9.30, H 4.87.
(5Z)-3-(3-Chlorobenzyl)-5-(3-nitrobenzylidene)furan-
2(5H)-one (18)
Root elongation assays on Petri dishes with seeds of Sorghum
bicolor and Cucumis sativus
M. p. 143.1 – 144.7 ◦C. – IR (KBr) ν = 3093, 3068,
3028, 1764 (C=O), 1654, 1607, 1528, 1453, 1348, 951,
816 cm−1. – 1H NMR (300 MHz, CDCl3): δ = 3.75 (s, 2 H,
7-H), 5.91 (s, 1 H, 6-H), 6.98 (s, 1 H, 4-H), 7.25 – 7.34 (m,
4 H, 2ꢀ-H/4ꢀ –H/5ꢀ-H/6ꢀ-H), 7.55 (dd, J = 8.4, J = 8.2 Hz, 1 H,
5ꢀꢀ-H), 8.12 (dt, J = 8.4, J = 1.2 Hz, 1 H, 4ꢀꢀ-H), 8.15 (dt, J =
8.2, J = 1.2 Hz, 1 H, 6ꢀꢀ-H), 8.41 (t, J= 1.2 Hz, 1 H, 2ꢀꢀ-H). –
13C NMR (75 MHz, CDCl3): δ = 31.83 (C-7), 111.45 (C-6),
123.05 (C-4ꢀꢀ), 125.08 (C-2ꢀꢀ), 127.36 (C-4ꢀ), 127.53 (C-6ꢀ),
129.11 (C-2ꢀ), 130.22 (C-5ꢀ), 134.52 (C-3ꢀ), 129.84 (C-5ꢀꢀ),
134.41 (C-1ꢀꢀ), 134.71 (C-3), 135.59 (C-6ꢀꢀ), 136.71 (C-1ꢀ),
139.12 (C-4), 148.57 (C-5), 149.15 (C-3ꢀꢀ), 170.52 (C-2). –
MS (EI 70 eV): m/z (%) = 341 (45) [M]+ (C18H12ClNO4),
343 (15) [M+2]+, 296 (57), 288 (11), 216 (46), 202 (20), 135
(22), 115 (100), 89 (89), 77 (25), 63 (55), 51 (18). – Anal.:
calcd. C 63.26, Cl 10.37, H 3.54; found C 63.11, Cl 10.52,
H 3.41.
The biological assay was carried out as previously de-
scribed [35] with seeds of S. bicolor and C. sativus at 10 ppm
and 100 ppm. Stock solutions at 100 ppm of each tested com-
pound were prepared as follows: Each compound was dis-
solved in xylene (24 µL), with surfactant Tween 80 (36 µL)
and pentan-3-one (12 µL). The resultant suspension was
shaken for 1 min and then transferred to a volumetric flask
and the volume supplemented with water to 50 mL. The re-
sultant suspension was sonicated for 5 min. The 10 ppm so-
lutions were prepared diluting the 100 ppm ones accordingly.
The biological assays were conducted in Petri dishes
(i. d. = 9 cm) lined with two sheets of filter paper. Groups
of twenty seeds along with 4 mL of the solution contan-
ing the compound to be tested were placed in Petri dishes.
The Petri dishes were sealed with Parafilm and incubated
◦
at 25 C under fluorescent light (8 × 40 W) in an incubator
for 3 d. Radicle length was measured and total germination
recorded. Seeds were considered to have germinated if a radi-
cle protruded at least 1 mm. Controls were included using
xylene, pentan-3-one and surfactant Twen 80. Each bioassay
was replicated five times in a completely randomized design.
The percentage of radicle growth inhibition was calculated
in relation to the root length of the control. The data were
analyzed using Tukey’s test at 0.05 probability level.
(5E)-3-(3-Chlorobenzyl)-5-(2,4,6-trimethoxybenzylidene)
furan-2(5H)-one (19)
M. p. 129.1 – 129.7 ◦C. – IR (KBr) ν = 3054, 2917,
2848, 1749 (C=O), 1600, 1583, 1467, 1456, 1333, 1205,
1156, 1119, 1035, 813 cm−1. – 1H NMR (300 MHz,
CDCl3): δ = 3.74 (s, 2 H, 7-H), 3.79 (s, 6 H, 2ꢀꢀ,6ꢀꢀ-OCH3),
3.81 (s, 3 H, 4ꢀꢀ-OCH3), 6.08 (s, 2 H, 3ꢀꢀ-H/5ꢀꢀ-H), 6.44
(s, 1 H, 6-H), 7.08 (s, 1 H, 4-H), 7.16 – 7.25 (m, 4 H,
2ꢀ-H/4ꢀ-H/5ꢀ-H/6ꢀ-H). – 13C NMR (75 MHz, CDCl3): δ =
31.74 (C-7), 55.47 (4ꢀꢀ- OCH3), 55.95 (2ꢀꢀ/6ꢀꢀ- OCH3), 90.91
(C-3ꢀꢀ/C5ꢀꢀ), 101.98 (C-6), 127.32 (C-4ꢀ), 127.47 (C-6ꢀ),
128.97 (C-2ꢀ), 129.25 (C-5ꢀ), 133.17 (C-3), 133.89 (C-3ꢀ),
136.39 (C-1ꢀ), 140.50 (C-4), 148.23 (C-5), 151.51 (C-2ꢀꢀ/6ꢀꢀ),
161.52 (C-4ꢀꢀ), 173.02 (C-2). – MS (EI 70 eV): m/z (%) = 386
(100) [M]+ (C21H19ClO5), 388 (34) [M+2]+, 351 (11), 343
Acknowledgements
We are grateful to the following Brazilian agencies: Con-
selho Nacional de Desenvolvimento Cient´ıfico e Tecnolo´gico
(CNPq) for research fellowships (to LCAB and AJD), and fi-
nancial support; Fundac¸a˜o de Amparo a` Pesquisa de Minas
Gerais (FAPEMIG) and FINEP for financial support. We also
thank Professor Antoˆnio Alberto Silva from the Plant Sci-
ence Department (UFV) for some support on the bioassays.
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