Synthesis and phytotoxicity evaluation of substituted para-benzoquinones

Article abstract of DOI:10.1071/CH02032

Sorgoleone (1) is one of the major constituents of sorghum root exudates. Sorgoleone is an allelochemical that reduces the growth of broad-leaf plants. The 3,5-dimethoxybenzylic alcohol (3) was used as starting material for the synthesis of 2-methoxy-6-(non-1-yl)benzo-1,4-quinone(9) in 69% yield. Acetylation of (9) with acetic anhydride gave the triacetate (10) in 82% yield. The triacetate (10) was then converted in two steps in 2-hydroxy-5-methoxy-3-(non-1-yl)benzo-1,4-quinone (11) and 2-acetoxy-5-methoxy-3-(non-1-yl)benzo-1,4-quinone (12) in 8% and 37% yield, respectively. Quinone (11) was obtained also by reaction of (12) with DBU in 63% yield. Alkylation of (3) and oxidation with chromic anhydride formed the new quinones (16) (17) and (18) in 23%, 16% and 12% overall yield, respectively. The effect of these quinones and sorgoleone (1) at concentrations of 5.5 μg g^-1 on the development of radicle and aerial parts of Cucumis sativus, Brachiaria decumbens, Hyptis lophanta, and Euphorbia heterophylla was tested.

Full text of DOI:10.1071/CH02032

Short Communication
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2003, 56, 625–630
Synthesis and Phytotoxicity Evaluation of Substituted
para-Benzoquinones
Larissa S. Lima,A Luiz Cláudio de A. Barbosa,A,C Elson S. de Alvarenga,A
Antônio J. DemunerA and Antônio A. da SilvaB
A Departamento de Química, Universidade Federal de Viçosa, 36571-000, Viçosa–MG, Brazil.
B Departamento de Fitotecnia, Universidade Federal de Viçosa, 36571-000, Viçosa–MG, Brazil.
C Author to whom correspondence should be addressed (e-mail: lcab@ufv.br).
Sorgoleone (1) is one of the major constituents of sorghum root exudates. Sorgoleone is an allelochemical that
reduces the growth of broad-leaf plants. The 3,5-dimethoxybenzylic alcohol (3) was used as starting material for
thesynthesisof2-methoxy-6-(non-1-yl)benzo-1,4-quinone(9)in69%yield.Acetylationof(9)withaceticanhydride
gave the triacetate (10) in 82% yield. The triacetate (10) was then converted in two steps in 2-hydroxy-5-methoxy-3-
(non-1-yl)benzo-1,4-quinone (11) and 2-acetoxy-5-methoxy-3-(non-1-yl)benzo-1,4-quinone (12) in 8% and 37%
yield, respectively. Quinone (11) was obtained also by reaction of (12) with DBU in 63% yield.Alkylation of (3) and
oxidation with chromic anhydride formed the new quinones (16) (17) and (18) in 23%, 16% and 12% overall yield,
respectively. The effect of these quinones and sorgoleone (1) at concentrations of 5.5 µg g−1 on the development of
radicle and aerial parts of Cucumis sativus, Brachiaria decumbens, Hyptis lophanta, and Euphorbia heterophylla
was tested.
Manuscript received: 8 February 2002.
Final version: 21 January 2003.
Introduction
assays[5,6] and its activity can even be compared with syn-
thetic herbicides such as diuron, atrazine, and metribuzin.[6]
The total synthesis of sorgoleone has been published by
Sargent and Wangchareontrakul.[7] Although some other
natural quinones have been synthesized, their phytotoxicity
have not been investigated.[8,9,16] Because of its phytotoxi-
city, sorgoleone can therefore serve as an excellent model
for the development of new synthetic herbicides. Thus, the
aim of this work was to prepare several new quinones and
evaluate their phytotoxicity in Cucumis sativus, Brachiaria
decumbens, Hyptis lophanta, and Euphorbia heterophylla.
Theculturesofsorghumhavebeeninvestigatedsincetheearly
1900s for their effects on plants succeeding them in the same
cultivated area. Allelochemicals liberated by sorghum plants
are produced during seed germination, and the production of
these compounds continues during the growth of the plant.[1]
Sorghum root exudate contains many hydrophilic and
hydrophobic organic compounds that produce allelopathic
effects,[2,7] its major constituents being sorgoleone (1) and
dihydrosorgoleone (2), Diagram 1. Dihydrosorgoleone is the
initial exudate, but it is easily oxidized to the more stable
sorgoleone.[3,4]
At a low concentration (10 µM), sorgoleone reduces
the growth of broad-leaf plants in hydroponic biological
Results and Discussion
Commercially available 3,5-dimethoxybenzylic alcohol (3),
used as starting material for the synthesis of new analogues
of sorgoleone, was converted into aldehyde (4) in 88% by
means of Swern oxidation[13] (Scheme 1). In order to extend
the side chain, aldehyde (4) was converted into alcohol (5) in
88% yield by a Grignard reaction using 1-bromooctane.
The alcohol 1-(3,4-dimethoxyphenyl)pentan-1-ol has
been deoxygenated in 77% yield by reaction with ZnI2/
NaCNBH3,[13] according to literature methods.[15,16]
Attempts to prepare hydrocarbon (8) in a one-pot reaction
from the corresponding alcohol (5), following these meth-
ods, failed. There was no reaction even when the mixture was
heated at 40˚C for 2 h.A possible reason for this failure is that
O
OH
Sorgoleone (1)
H3CO
O
OH
OH
Dihydrosorgoleone (2)
H3CO
OH
Diagram 1.
© CSIRO 2003
10.1071/CH02032
0004-9425/03/060625

626
L. S. Lima et al.
OCH3
OCH3
OCH3
i
ii
CH3
7
H3CO
OH
H3CO
CHO
H3CO
OH
iii
OCH3
(3)
O
(4)
(5)
OCH3
v
iv
CH3
CH3
CH3
H3CO
H3CO
H3CO
8
6
8
O
(9)
(8)
(6)
+
vi
H3C
OCH3
7
H3CO
OAc
OAc
OCH3
H3CO
CH3
H3CO
7CH3
8
OAc
vii
(10)
(7)
O
O
O
OAc
OH
+
CH3
CH3
H3CO
H3CO
8
8
O
(11)
(12)
viii
Scheme 1. Reagents and conditions: (i) (CClO)2, CH2Cl2; DMSO, −78◦C, 1.5 h; TEA, 25◦C, 5 h;
(ii) THF, C8H17MgBr, 2 h, 88%; (iii) PTSA, benzene, 60◦C, 6 h, 74% of (6), 10% of (7); (iv) H2,
Pd/C 10%, ethyl acetate, 5 h, 93%; (v) CrO3, AcOH, H2O, 25◦C, 2 d, 69%; (vi) Ac2O, H2SO4, 25◦C,
16 h, 82%; (vii) (a) LiAlH4, THF, 70◦C, 6 h; (b) FeCl3, benzene, 25◦C, 3 h, 8% of (11) and 37% of
(12); (viii) DBU, THF, 25◦C, 30 min, 64%.
none of the methoxy groups in alcohol (5) are located para
to the alkyl chain, to facilitate the removal of the hydroxyl
group.
recrystallization; quinone (9) was obtained as yellow crystals
in 69% yield.[18,19] Thiele acetoxylation[18,19] of quinone (9)
gave the triacetate (10) in 82% yield.
Alcohol (5) was then converted into hydrocarbon com-
pound (8) via alkene (6). The trans-alkene (6), which is
thermodynamically more stable than the cis-alkene, was
prepared in 74% yield by reaction of the alcohol (5) with p-
toluenesulphonic acid.[17] The trans geometry was confirmed
by the 1H coupling constant of H1ꢀ and H2ꢀ (J 15.7 Hz).Also
isolated was the dimer (7) in 10% yield. The structures of
these compounds were elucidated by IR, 1H and 13C NMR,
and EIMS.
In the synthesis of metachrominA all three acetate groups
were removed,[19] in good yield, from 1,2,4-triacetoxy-
5-methoxy-3-[3-methyl-5-(1,3-dimethyl-2-methylene cyclo-
hex-1-yl)-pent-2-enyl]benzenebyLiAlH4 reductionfollowed
by FeCl3 oxidation. Attempts to convert triacetate (10) into
quinone (11) following this procedure afforded the required
product (11) in only 8% yield and the unexpected acetylated
quinone (12) in 37% yield. The saturated hydrocarbon chain
in the triacetate (10) is probably hindering the acetoxy group
from attack by the hydride, whereas the triacetate precur-
sor of metachromin A, completely reduced by LiAlH4, has a
more rigid (E)-alkene geometry which could not hinder any
acetoxy group.
As the yield for the synthesis of the quinone (11) from
(10) was low, the conversion of the acetate (12) into (11)
was attempted. Compound (12) was then treated with 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) in THF under nitro-
gen to give (11) in 64% yield.[19] Thus the overall yield for
the synthesis of (11) from the triacetate (10) increased from
8% to 32%.
The 1H NMR spectrum of the dimer (7) showed two doub-
lets at the aromatic region. One at δ 6.34 (J 2.1 Hz) was
assigned to H2 and H6, and one at δ 6.44 (J 2.1 Hz) to H4
and H8.Atoms H9 and H10 gave a triplet at δ 4.33 (J 3.9 Hz).
This symmetric molecule showed 17 signals in its 13C NMR
spectrum, which corresponds to half the number of carbon
atoms in its structure.
Hydrogenation of alkene (6) in the presence of 10%
palladium on carbon afforded (8) in 93% yield. Com-
pound (8) was oxidized by chromic anhydride in acetic
acid and after flash column chromatography followed by

Synthesis and Phytotoxicity of Substituted para-Benzoquinones
627
Table 1. Effect of quinones (1),(9),(11),(12),(16)–(18) at 5.5 µg g−1
on the development of roots and aerial parts of four plant species
Plants in plastic pots, using sand as substrate
(13) n = 3; 65%
(14) n = 5; 55.5%
(15) n = 7; 50%
OCH3
(3)
OCH3
i
OH
CH3
Treatment
Aerial parts
Roots
O
H3CO
H3CO
n
(products) Mass [mg]A Inhibition [%] Mass [mg]A Inhibition [%]
ii
Cucumis sativus
(16) n = 3; 36%
(17) n = 5; 29.3%
(18) n = 7; 24.2%
Control
1
9
11
12
16
17
18
5.40ab
5.32ab
4.94c
5.06bc
5.62a
5.14bc
5.66a
5.20bc
3.43
0.00
1.48
8.52
6.29
−4.07
4.81
−4.81
3.70
–
1.69bc
1.58ef
1.73ab
1.55fg
1.53g
1.65cd
1.61de
1.76a
1.33
0.00
6.51
−2.36
8.28
9.47
2.36
4.73
−4.14
–
O
CH3
O
H3CO
n
O
Scheme 2. Reagents and conditions: (i) alkyl bromide: 1-bromo-
butane (n = 3), 1-bromohexane (n = 5), or 1-bromooctane (n = 7),THF,
NaH, imidazole, reflux, 6 h, 65% of (13), 56% of (14), and 50%
of (15) respectively; (ii) CrO3, AcOH, H2O, 0◦C, 30 min, 36% of (16),
29% of (17), and 24% of (18), respectively.
CV [%]
Euphorbia heterophylla
Control
1
9
11
12
16
17
1.51a
1.50a
1.49a
1.53a
1.52a
1.50a
1.51a
1.56a
1.59
0.00
0.66
1.32
−1.32
−0.66
0.66
0.59a
0.59a
0.52b
0.61a
0.62a
0.57a
0.58a
0.58a
4.15
0.00
0.00
11.86
−3.38
−5.08
3.39
1.69
1.69
–
We envisaged that the benzylic alcohol (3) could be used
to prepare more polar quinones, analogues of sorgoleone, for
biological evaluation. This alcohol (3) was then converted, in
good yields, into the ethers (13)–(15) according to the proce-
dures described[21] (Scheme 2). These ethers were converted
into the corresponding quinones (16)–(18) using the same
methods described for the synthesis of (9).[18,19] As for the
ethers, the spectroscopic data of these quinones differ from
each other only by the aliphatic chain.
0.00
18
CV [%]
−3.31
–
Hyptis lophanta
Control
1
9
11
12
16
17
0.59bc
0.00
1.69
8.47
8.47
3.39
−8.47
−6.78
1.69
–
0.50a
0.48a
0.54a
0.50a
0.47a
0.48a
0.55a
0.49a
7.48
0.0
4.0
0.58cd
0.54d
0.54d
0.57cd
0.64a
0.63ab
0.58cd
3.74
−8.0
0.0
6.0
4.0
Bioassays
−1.0
The effect of compounds (1), (9), (11), (12), and (16)–(18) at
5.5 µg g−1 on the development of the aerial parts and roots of
Cucumis sativus, Euphorbia heterophylla, Hyptis lophanta,
and Brachiaria decumbens were evaluated, and the results are
shown in Table 1.
For Cucumis sativus, compound (9) was the only one that
caused a significant inhibition (8.52%) on the development
of the aerial parts; it was even more active than sorgoleone.
For the roots of this plant, compounds (1), (11), (12), and
(17) caused a significant growth inhibition. In this case only
the acetate (12) was more active than sorgoleone. A small
stimulatory effect (4.14%) was caused by compound (18).
For Euphorbia heterophylla only (9) showed activity with
a significant root inhibition (11.86%). All the other com-
pounds, including the natural quinone sorgoleone, were not
active under the tested conditions.
18
CV [%]
2.0
–
Brachiaria decumbens
Control
1
9
11
12
16
17
1.40a
1.36a
1.32a
1.32a
1.48a
1.34a
1.26a
1.28a
7.83
0.00
2.86
5.71
5.71
−5.71
4.28
10.00
8.57
–
0.74ab
0.76a
0.60b
0.74ab
0.74ab
0.70ab
0.66ab
0.76a
9.99
0.00
−2.70
18.92
0.00
0.00
5.40
10.81
−2.70
–
18
CV [%]
A Means appearing in the same column with the same letter are not
significantly different at P = 0.05% according to Tukey’s test.
note that some of them, especially (9), were more active than
the natural herbicide sorgoleone.[6]
For Hyptis lophanta none of the compounds had any
effect on the root development, but compounds (9) and
(11) caused a significant inhibition (8.47% in both cases)
on the development of the aerial parts, although this was
not significantly different from the inhibition caused by sor-
goleone (1.69%). Compound (16) caused a small (8.47%) but
significant stimulatory growth on the aerial parts.
These results show that the triene unit in the side-chain of
sorgoleone, which is difficult to prepare, is not required for
biological activity. In general, the introduction of the oxygen
atom at the side-chain, compounds (16)–(18), had little effect
on the activity.
For Brachiaria decumbens only compound (9) caused a
significant inhibition (18.92%) on root development.
Although under the tested conditions none of the com-
pounds caused a very high inhibition on the development of
the roots or aerial parts of the plants, it is very important to
Conclusion
The biological tests showed that quinones like (9), which are
easiertosynthesizethanthenaturalsorgoleone, showedbetter

628
L. S. Lima et al.
activity. The chemistry described here can be used for the
preparation of a larger number of quinones for structure–
activity relationship studies directed towards the discovery of
new compounds with potential commercial use as herbicides.
1,3-Dimethoxy-5-[(E)-non-1-en-1-yl]benzene (6) and
1,3,5,7-Tetramethoxy-9,10-(dioct–1-yl)-9,10-dihydroanthracene (7)
To a two-neck round-bottomed flask, 1-(3,5-dimethoxyphenyl)nonan-
1-ol (5) (500 mg, 1.78 mmol) dissolved in benzene (20 mL) was added,
followed by p-toluenesulphonic acid (PTSA; ∼50 mg).The mixture was
stirred at 60◦C for 6 h, diluted with ethyl acetate (20 mL), then washed
with distilled water (2 × 15 mL) and brine (2 × 15 mL). The organic
layer was dried with anhydrous MgSO4, filtered, and the filtrate con-
centrated to give an oil. This oily residue was purified by flash column
chromatography eluting with a mixture of hexane/diethyl ether (40 : 1
v/v) to afford the alkene (6) (yellow oil, 345 mg, 74% yield) and the
dimer (7) (white crystals, 47.8 mg, 10% yield).
Experimental
Reagents and solvents were purified, when necessary, according to lit-
erature procedures.[11] Flash column chromatography was performed
using Crosfield Sorbil C60 (32–63 µm) apparatus. The melting points
were determined on a electrothermal digital apparatus with correction.
Infrared spectra were recorded on a Perkin–Elmer Spectrum 1000 grat-
ing spectrometer, employing KBr disks or liquid film on NaCl. 1H and
13C NMR spectra were recorded in a Bruker DPX 200 (200 MHz) and
Varian Mercury 300 (300 MHz) spectrometers. Tetramethylsilane was
used as internal standard (δ = 0) and CDCl3 as solvent.
(6) νmax (film)/cm−1 2998, 2925, 2853, 1594, 1450, 1426, 1340,
1270, 1200, 1150, 1068, 850. δH (200 MHz) 0.88 (t, J 6.7, CH3), 1.28–
1.45 (m, 5 × CH2), 2.19 (ql, J 6.1, H3ꢀ), 3.85 (s, 2 × OCH3), 6.19 (dt,
J 15.7, 6.1, H2ꢀ), 6.31 (d, J 15.7, H1ꢀ), 6.32 (t, J 2.3, H2), 6.5 (d, J
2.3, H4, H6). δC (50 MHz) 14.1 (C9ꢀ), 22.7 (C7ꢀ, C8ꢀ), 29.2 (C5ꢀ*),
29.3 (C6ꢀ*), 31.9 (C4ꢀ), 33.0 (C3ꢀ), 55.3 (2 × OCH3), 99.1 (C2), 103.1
(C4*), 104.0 (C6*), 129.7 (C2ꢀ), 131.9 (C1ꢀ), 140.0 (C5), 160.8 (C1,
C3). *The assignments could be inverted. m/z 262 (M+•, 10%), 191
(20), 177 (20), 164 (10), 152 (100), 121 (8), 91 (40).
3,5-Dimethoxybenzaldehyde (4)
(7) mp 116–116.5◦C (found: C, 77.71; H, 10.14%; C32H48O4
requires C, 77.38; H, 9.74%). νmax (KBr)/cm−1 2995, 2949, 2922,
2854, 1607, 1585, 1486, 1435, 1350, 1270, 1220, 1150, 1100, 950, 850.
δH (300 MHz) 0.45–0.56 (m, 2 × CH2, H3ꢀ), 0.82 (t, J 6.8, 2 × CH3),
0.9–1.7 (m, 12 × CH2), 2.0–2.2 (m, 2 × CH2, H1ꢀ), 3.83 (s, 3-OCH3,
7-OCH3*), 3.86 (s, 1-OCH3, 5-OCH3*), 4.33 (t, J 3.7, H9, H10), 6.34
(d, J 2.1, H2, H6), 6.44 (d, J 2.1, H4, H8). δC (75 MHz) 14.1 (C8ꢀ), 22.6
(C7ꢀ*), 23.4 (C3ꢀ*), 29.2 (C4ꢀ*), 29.2 (C2ꢀ*), 29.8 (C5ꢀ*), 31.8 (C6ꢀ*),
37.4 (C9, C10), 38.4 (C1ꢀ), 55.1 (2 × OCH3*), 55.2 (2 × OCH3*), 96.2
(C2, C6), 103.1 (C4, C8), 119.2 (C12, C13), 140.5 (C11, C14), 157.2
(C1, C5), 158.2 (C3, C7). *The assignments could be inverted.
To a round-bottomed flask equipped with a CaCl2 tube, dry CH2Cl2
(30 mL) and oxallyl chloride (0.60 mL, 6.5 mmol) were added. The
solution was kept at −78◦C and dimethyl sulfoxide (DMSO; 1 mL,
13 mmol) in dry dichloromethane (1 mL) was added. The reaction mix-
ture was stirred for 30 min and 3,5-dimethoxybenzylic alcohol (3) (1.0 g,
6.0 mmol) was added. After 1 h, triethylamine (TEA; 4.2 mL, 30 mmol)
was added and the reaction mixture stirred at room temperature for 5 h.
After this time, water (40 mL) was added and the mixture extracted with
CH2Cl2 (5 × 20 mL). The organic phase was washed with an aqueous
solution of HCl (1 M, 2 × 20 mL), 5% aqueous NaHCO3 (2 × 20 mL),
and brine (20 mL), dried over MgSO4, and concentrated under reduced
pressure to yield an yellow oil. This oil was purified by flash chromato-
graphy (hexane/diethyl ether, 3 : 1 v/v) to afford the required aldehyde
(4). White solid, 868 mg, 88% yield, mp 54–55◦C. νmax (film)/cm−1
3525, 3500, 3400, 3000, 2800, 1710, 1600, 1475, 1375, 1350, 1300,
1200, 1060, 950, 900, 825, 700. δH (300 MHz) 3.80 (s, 2 × OCH3),
6.70 (t, J 2.4, H4), 7.00 (d, J 2.4, H2, H6), 9.90 (s, CHO). δC (75 MHz)
55.6 (2 × OCH3), 107.1 (C2, C6), 107.2 (C4), 138.4 (C1), 161.3 (C3,
C5), 191.9 (C O). m/z 166 (M+•, 100%), 165 (70), 137 (9), 135 (35),
95 (20), 63 (20).
1,3-Dimethoxy-5-(non-1-yl)benzene (8)
The alkene (6) (100 mg, 0.38 mmol) was dissolved in ethyl acetate
(6 mL) in a round-bottomed flask followed by addition of 10% Pd/C
(10 mg). The mixture was stirred magnetically under an H2 atmosphere
for 5 h. The catalyst was filtered and the solution concentrated in a
rotary evaporator to give (8) as an yellow oil (93.3 mg, 93% yield). νmax
(film)/cm−1 2930, 2880, 1600, 1420, 1380, 1300, 1200, 1160, 1120,
1060, 820. δH (200 MHz) 0.87 (t, J 6.7, CH3), 1.26–1.40 (m, 6 × CH2),
1.55–1.59 (m, H2ꢀ), 2.54 (dd, J 7.3, 8.0, H1ꢀ), 3.73 (s, 2×OCH3), 6.28
(t, J 2.2, H2), 6.34 (d, J 2.2, H4, H6). δC (50 MHz) 14.1 (C9ꢀ), 22.7
(C8ꢀ), 29.4 (C3ꢀ*), 29.6 (C4ꢀ*), 29.6 (C5ꢀ, C6ꢀ*), 31.3 (C2ꢀ), 31.9 (C7ꢀ),
1-(3,5-Dimethoxyphenyl)nonan-1-ol (5)
36.3 (C1ꢀ), 55.2 (2 × OCH3), 97.5 (C2), 106.5 (C4, C6), 145.4 (C5),
To a three-neck round-bottomed flask, magnesium (80 mg, 3.3 mmol)
and some crystals of iodine in dry THF (2 mL) were added. The system
was stirred under nitrogen for 20 min, when 1-bromooctane (0.5 mL,
3.0 mmol) dissolved in dry THF (10 mL) was added. When half of this
solution had been added, it was diluted with a further 10 mL of THF
before completing the addition of 1-bromooctane. The formation of the
Grignard reagent was indicated when the reaction mixture changed from
yellow to grey. After 20 min, 3,5-dimethoxybenzaldehyde (4) (100 mg,
0.60 mmol) in dry THF (2 mL) was added. Saturated NH4Cl (15 mL)
was added to the reaction mixture after 2 h, and the organic solvent evap-
orated in the rotary evaporator. The residue was extracted with CH2Cl2
(4 × 20 mL), and the combined organic layers were washed with brine
(2 × 20 mL). The dichloromethane solution was dried with anhydrous
MgSO4 and concentrated in the rotary evaporator giving an yellow oil.
This oil was purified by flash column chromatography eluting with hex-
ane/diethyl ether (2 : 1 v/v) affording the desired alcohol (5). 149 mg,
88% yield. νmax (film)/cm−1 3380, 2930, 2850, 1600, 1450, 1375, 1200,
1150, 1060, 850. δH (300 MHz) 0.87 (t, J 7.2, CH3), 1.21–1.28 (m,
6 × CH2), 1.52 (q, J 6.6, H2), 1.75 (sl, OH), 3.77 (s, 2 × OCH3), 4.59
(t, J 6.4, H1), 6.35 (t, J 2.1, H4ꢀ), 6.48 (d, J 2.1, H2ꢀ, H6ꢀ). δC (75 MHz)
14.3 (C9), 22.9 (C8), 26.0 (C3), 29.5 (C5*), 29.6 (C4*), 32.1 (C6), 33.0
(C7), 39.2 (C2), 55.5 (2 × OCH3), 77.9 (C1), 99.3 (C4ꢀ), 104.0 (C2ꢀ,
C6ꢀ), 147.6 (C1ꢀ), 160.8 (C3ꢀ, C5ꢀ). *The assignments could be inverted.
m/z 97 (4%), 84 (20), 69 (50), 56 (100).
•
160.7 (C1, C3. *The assignments could be inverted. m/z 264 (M+
,
3%), 194 (2), 165 (10), 152 (100), 91 (10), 77 (15).
2-Methoxy-6-(non-1-yl)-benzo-1,4-quinone (9)
To a round-bottomed flask chromic anhydride (773 mg, 7.57 mmol),
acetic acid (15 mL) and a few drops of distilled water was added,
up to complete dissolution. The oxidizing mixture was stirred at
0◦C for 30 min. This mixture was then transferred to another round-
bottomed flask containing (8) (1.0 g, 3.78 mmol) dissolved in acetic
acid (6 mL). The reaction mixture was stirred at room temperature for
2 d. The mixture was diluted with distilled water (20 mL) and extracted
with CH2Cl2 (4 × 20 mL). The combined organic layers were washed
with brine (2 × 20 mL), dried with anhydrous magnesium sulfate, fil-
tered, and concentrated in the rotary evaporator. The yellow oil was
purified by flash column chromatography (hexane/diethyl ether, 5 : 1)
to give the quinone (9), which was recrystallized in a mixture of
dichloromethane/hexane(yellowcrystals, 690mg, 69%yield). mp69.0–
69.8◦C. νmax (KBr)/cm−1 2912, 2850, 1681, 1653, 1602, 1473, 1241,
1177, 1042, 906. δH (200 MHz) 0.87 (t, J 6.7, CH3), 1.26–1.66 (m,
7 × CH2), 2.46 (dt, J 1.3, 6.8, H1ꢀ), 3.81 (s, OCH3), 5.88 (d, J 2.3,
H3), 6.48 (dt, J 2.3, 1.3, H5). δC (50 MHz) 14.1 (C9ꢀ), 22.7 (C8ꢀ), 27.7
(C2ꢀ*), 28.7 (C3ꢀ*), 29.2 (C1ꢀ*), 29.3 (C4ꢀ*), 29.3 (C6ꢀ*), 29.4 (C5ꢀ*),
31.9 (C7ꢀ), 56.3 (OCH3), 107.1 (C3), 132.9 (C5), 147.6 (C6), 158.9

Synthesis and Phytotoxicity of Substituted para-Benzoquinones
629
(C2), 182.1 (C4), 187.7 (C1). * The assignments could be inverted. m/z
(OCH3), 101.1 (C6), 133.1 (C3), 151.1 (C5), 164.2 (C2), 167.7 (C1),
178.1 (O2CCH3), 179.4 (C4). * The assignments could be inverted.
264 (M+•, 5%), 179 (10), 158 (50), 124 (15), 109 (15), 69 (100), 53 (80).
1,2,4-Triacetoxy-5-methoxy-3-(non-1-yl)benzene (10)
1-(Butoxymethyl)-3,5-dimethoxybenzene (13)
To a round-bottomed flask, quinone (9) (500 mg, 1.89 mmol), acetic
anhydride (10 mL), and concentrated sulfuric acid (5 drops) was added.
The reaction mixture was stirred at room temperature for 16 h. The mix-
turewascooledto0◦C, dilutedwithdistilledwater(20 mL)andextracted
with diethyl ether (4 × 20 mL).The combined organic layers was washed
with distilled water (2 × 15 mL) and NaHCO3 5% (2 × 15 mL). The
ethereal solution was dried with anhydrous MgSO4, filtered, and con-
centrated in the rotary evaporator. The residue was purified by flash
column chromatography (hexane/diethyl ether, 3 : 2 v/v) to afford (10)
as an yellow oil (633 mg, 82% yield). νmax (film)/cm−1 2926, 2926,
2854, 1770, 1598, 1480, 1380, 1270, 1100, 1000, 930. δH (200 MHz)
0.87 (t, J 6.5, CH3), 1.25–1.41 (m, 7 × CH2), 2.26 (s, 1-CH3*), 2.29 (s,
2-CH3*), 2.31 (s, 4-CH3*), 2.41 (dd, J 7.0, 8.3, H1ꢀ), 3.78 (s, OCH3),
6.79 (s, H6). δC (50 MHz) 14.0 (C9ꢀ), 20.2 (C8ꢀ), 20.4 (1-CH3*), 20.7 (4-
CH3*), 22.6 (2-CH3), 25.3 (C8ꢀ), 28.9 (C2ꢀ*), 29.2 (C3ꢀ*), 29.3 (C4ꢀ),
29.4 (C5ꢀ*), 29.6 (C6ꢀ*), 31.9 (C7ꢀ), 56.2 (OCH3), 104.8 (C6), 130.2
(C3), 135.9 (C4), 140.2 (C2), 149.2 (C1, C5), 168.1 (1-C O*), 168.3
(2-C O*), 168.4 (4-C O). * The assignments could be inverted.
A mixture of 3,5-dimethoxybenzylic alcohol (400 mg, 2.37 mmol),
imidazole (80 mg), and NaH 80% (213 mg, 7.11 mmol) in dry THF
(20 mL) was refluxed under an N2 atmosphere for 6 h. KI (0.05 g) and
1-bromobutane (649 g, 4.74 mmol) were added to the reaction mixture.
The reaction mixture was stirred at 70◦C for a further 3 h and then for
12 h at room temperature. Distilled water (20 mL) was added to the
mixture and it was extracted with CH2Cl2 (4 × 20 mL). The combined
organic layers was washed with brine (2 × 20 mL), dried over anhydrous
MgSO4, and filtered. The filtrate was concentrated in the rotary evap-
orator and the residue was purified by flash column chromatography
eluting with hexane/diethyl ether (20 : 1 v/v) to give the ether (13) as
an yellow oil (345 mg, 65% yield). νmax (film)/cm−1 2957, 2934, 2865,
2800, 1598, 1464, 1430, 1361, 1320, 1205, 1155, 1103, 1067, 823. δH
(300 MHz) 0.83 (t, J 7.0, CH3), 1.2–1.6 (m, 2 × CH2), 3.47 (t, J 6.6,
H2ꢀ), 3.81 (s, 2 × OCH3), 4.42 (s, H1ꢀ), 6.38 (t, J 2.1, H2), 6.51 (d,
J 2.4, H4, H6). δC (75 MHz) 14.0 (C5ꢀ), 19.4 (C4ꢀ), 31.9 (C3ꢀ), 55.3
(2 × OCH3), 70.2 (C2ꢀ), 72.8 (C1ꢀ), 99.5 (C2), 105.2 (C4, C6), 148.0
(C5), 160.8 (C1, C3). m/z 224 (M+•, 2%), 167 (2), 152 (100), 139 (5),
123 (5), 91 (20), 77 (30).
2-Hydroxy-5-methoxy-3-(non-1-yl)benzo-1,4-quinone (11) and
2-Acetoxy-5-methoxy-3-(non-1-yl)benzo-1,4-quinone (12)
1-[(Hexyloxy)methyl]-3,5-dimethoxybenzene (14)
To a two-neck round-bottomed flask LiAlH4 (85 mg, 2.12 mmol) and
dry THF (20 mL) were added and stirred under an N2 atmosphere. To
this mixture was added (10) (300 mg, 1.06 mmol) dissolved in dry THF
(5 mL). The reaction mixture was stirred at 70◦C for 6 h. The heating
source was removed and ethyl acetate (5 mL) was added to the reac-
tion mixture to destroy the unreacted LiAlH4. The mixture was diluted
with distilled water (15 mL) and the organic solvents were removed in
the rotary evaporator. The aqueous residue was extracted with CH2Cl2
(4 × 10 mL) and the combined organic layers was washed with brine
(2 × 10 mL). The CH2Cl2 solution was dried with anhydrous MgSO4,
filtered, and concentrated in the rotary evaporator yielding an yellow
solid (89% yield).
As described above in the synthesis of (13), the reaction of (3) (600 mg,
3.55 mmol), 80% NaH (333 mg, 8.88 mmol), and 1-bromohexane
(1.46 g, 8.85 mmol) afforded (14) as an yellow oil (497 mg, 56% yield).
νmax (film)/cm−1 2956, 2931, 2857, 1597, 1458, 1429, 1298, 1205,
1155, 1104, 1066, 832. δH (300 MHz) 0.88 (t, J 7.2, CH3), 1.25–1.66
(m, 4 × CH2), 3.45 (t, J 6.6, H2ꢀ), 3.82 (s, 2 × OCH3), 4.40 (s, H1ꢀ),
6.37 (t, J 2.1, H2), 6.50 (d, J 2.1, H4, H6). δC (75 MHz) 14.3 (C7ꢀ), 22.9
(C6ꢀ), 26.2 (C4ꢀ), 30.0 (C3ꢀ), 32.0 (C5ꢀ), 55.6 (2 × OCH3), 70.8 (C2ꢀ),
73.0 (C1ꢀ), 99.8 (C2), 105.5 (C4, C6), 141.4 (C5), 161.0 (C1, C3). m/z
166 (2%), 152 (100), 139 (5), 123 (5), 91 (20), 77 (30).
1,3-Dimethoxy-5-[(octyloxy)methyl]benzene (15)
To a solution of this solid in benzene (5 mL), 1% FeCl3 (3.0 mL)
was added. The reaction mixture was stirred at room temperature for
3 h, and then extracted with ethyl acetate (4 × 10 mL). The combined
organic layers was washed with brine (2 × 10 mL), dried over anhydrous
MgSO4, filtered, and concentrated in the rotary evaporator. The residue
obtained was purified by flash column chromatography (hexane/diethyl
ether, 1 : 2 v/v) giving (11) as yellow crystals (17.3 mg, 8% yield) and
(12) as orange crystals (88.9 mg, 37% yield).
As described above in the synthesis of (13), the reaction of (3) (500 mg,
2.96 mmol), 80% NaH (222 mg, 7.41 mmol), and 1-bromooctane
(1.40 g, 7.41 mmol) gave (15) as an yellow oil (416 mg, 50% yield).
νmax (film)/cm−1 2998, 2927, 2854, 1598, 1464, 1429, 1359, 1295,
1204, 1155, 1105, 1067, 832. δH (300 MHz) 0.87 (t, J 6.9, CH3), 1.26–
1.67 (m, 6 × CH2), 3.45 (t, J 6.8, H2ꢀ), 3.82 (s, 2 × OCH3), 4.40 (s,
H1ꢀ), 6.37 (t, J 2.4, H2), 6.50 (d, J 2.1, H4, H6). δC (75 MHz) 14.1
(C9ꢀ), 22.7 (C8ꢀ), 26.2 (C4ꢀ), 29.3 (C6ꢀ*), 29.4 (C3ꢀ*), 29.8 (C5ꢀ*), 31.8
(C7ꢀ), 55.3 (2 × OCH3), 70.5 (C2ꢀ), 72.7 (C1ꢀ), 99.5 (C2), 105.2 (C4,
C6), 141.2 (C5), 160.8 (C1, C3). * The assignments could be inverted.
m/z 280 (M+•, 2%), 152 (100), 91 (20), 77 (25).
Conversion of (12) into (11)
A mixture of the monoacetate (12) (80 mg, 0.24 mmol) and DBU (3
drops) dissolved in dryTHF (10 mL) was stirred at room temperature for
30 min. The reaction was quenched with 2 M HCl (5 mL). The mixture
was extracted with CH2Cl2 (3 × 20 mL), dried over anhydrous MgSO4,
andfiltered.Thefiltratewasconcentratedintherotaryevaporatorandthe
residue was purified by flash column chromatography (hexane/diethyl
ether, 1 : 1 v/v) to give (11) as yellow crystals (43.8 mg, 63% yield).
(11) mp 89.5–90.9◦C. νmax (KBr)/cm−1 3344, 2920, 2851, 1661,
1635, 1597, 1443, 1384, 1312, 1205, 1115, 1067. δH (300 MHz) 0.87
(t, J 6.6, CH3), 1.25–1.68 (m, 7 × CH2), 1.44–1.59 (s, OH), 2.44 (dd,
J 6.9, 7.8, H1ꢀ), 3.86 (s, OCH3), 5.99 (s, H6). δC (75 MHz) 14.1 (C9ꢀ),
22.6 (C1ꢀ), 22.7 (C8ꢀ), 28.1 (C2ꢀ), 29.3 (C3ꢀ), 29.4 (C4ꢀ*), 29.5 (C5ꢀ*),
29.6 (C6ꢀ*), 31.9 (C7ꢀ), 56.8 (OCH3), 102.2 (C6), 119.3 (C3), 151.6
(C5), 161.1 (C2), 181.7 (C1), 182.9 (C4). * The assignments could be
inverted.
2-(Butoxymethyl)-6-methoxybenzo-1,4-quinone (16)
To a round-bottomed flask chromic anhydride (340 mg, 3.33 mmol),
acetic acid (10 mL), and a few drops of distilled water were added
up to complete dissolution of the chromic anhydride. The mixture was
stirred at 0◦C for 30 min.This mixture was transferred to another round-
bottomed flask containing (13) (300 mg, 1.33 mmol) dissolved in acetic
acid (10 mL). The reaction mixture was stirred at room temperature
for 30 h. Distilled water (20 mL) was added to the mixture and it was
extracted with CH2Cl2 (4 × 20 mL). The combined organic layers was
washed with brine (2 × 10 mL), dried over anhydrous MgSO4, and fil-
tered. The filtrate was concentrated in the rotary evaporator and the
residue purified by flash column chromatography (hexane/diethyl ether
3 : 1 v/v) to give the quinone (16) as an yellow oil (108 mg, 36% yield).
νmax (film)/cm−1 2958, 2870, 1677, 1652, 1602, 1458, 1293, 1244,
1183, 1053, 904. δH (300 MHz) 0.94 (t, J 7.2, CH3), 1.26–1.64 (m,
2 × CH2), 3.55 (t, J 6.6, H2ꢀ), 3.83 (s, OCH3), 4.35 (d, J 2.1, H1ꢀ),
5.90 (d, J 2.4, H3), 6.77 (q, J 2.1, H5). δC (75 MHz) 13.7 (C5ꢀ), 19.3
(C4ꢀ), 31.7 (C3ꢀ), 56.3 (OCH3), 65.8 (C2ꢀ), 71.4 (C1ꢀ), 107.3 (C3), 132.0
Compound (12) mp 115.7–117.4◦C. νmax (KBr)/cm−1 3064, 2949,
2917, 2850, 1763, 1684, 1654, 1588, 1369, 1233, 1194, 1161. δH
(300 MHz) 0.87 (t, J 6.7, H9ꢀ), 1.17–1.48 (m, 7 × CH2), 2.33 (s,
O2CCH3), 2.38 (dd, J 7.0, 7.7, H1ꢀ), 3.85 (s, OCH3), 5.73 (s, H6).
δC (75 MHz) 14.1 (C9ꢀ), 20.2 (O2CCH3), 22.7 (C2ꢀ), 23.9 (C8ꢀ), 28.2
(C1ꢀ), 29.2(C3ꢀ*), 29.3 (C4ꢀ*), 29.4 (C5ꢀ*), 29.5 (C6ꢀ*), 31.9 (C7ꢀ), 57.1

630
L. S. Lima et al.
(C5), 144.0 (C6), 158.7 (C2), 181.6 (C4), 187.3 (C1. m/z 168 (50%),
152 (10), 140 (20), 123 (30), 95 (20), 69 (100), 57 (80).
Acknowledgments
We thank the Brazilian Agencies: Conselho Nacional de
Desenvolvimento Científico e Tecnológico (CNPq) for a
research fellowship to L.C.A.B. and a research grant
(CNPq/PADCT); Coordenação de Aperfeiçoamento de Pes-
soal de Nível Superior (CAPES) for a M.Sc. studentship to
L.S.L.; and Fundação de Amparo à Pesquisa do Estado de
Minas Gerais (FAPEMIG) for financial support. We would
like to thank Professor John Mann (Queens University of
Belfast) for proofreading this paper.
2-[(Hexyloxy)methyl]-6-methoxybenzo-1,4-quinone (17)
As described above in the synthesis of (16), the reaction of (14) (500 mg,
1.98 mmol) and chromic anhydride (398 mg, 3.90 mmol) afforded (17)
as an yellow oil (147 mg, 29% yield). νmax (film)/cm−1 3068, 2933,
2860, 1676, 1652, 1626, 1600, 1466, 1353, 1322, 1237, 1181, 1137,
1041, 910. δH (300 MHz) 0.88 (t, J 7.0, CH3), 1.22–1.41 (m, 3 × CH2),
1.58–1.64 (m, H3ꢀ), 3.53 (t, J 6.3, H2ꢀ), 3.83 (s, OCH3), 4.35 (d, J 2.1,
H1ꢀ), 5.90 (d, J 2.1, H3), 6.76 (q, J 2.1, H5). δC (75 MHz) 14.0 (C7ꢀ),
22.6 (C6ꢀ), 25.8 (C4ꢀ*), 29.6 (C3ꢀ*), 31.6 (C5ꢀ*), 56.3 (OCH3), 65.7
(C2ꢀ), 71.7 (C1ꢀ), 107.3 (C3), 132.0 (C5), 144.0 (C6), 158.6 (C2), 181.6
(C4), 187.3 (C1). * The assignments could be inverted. m/z 168 (75%),
152 (20), 140 (17), 123 (30), 95 (25), 80 (30), 69 (100), 55 (90).
References
[1] O. Panasiuk, D. D. Bills, G. R. Leather, J. Chem. Ecol. 1986,
12, 1553.
[2] J. A. Rasmussen, A. M. Hejl, F. A. Einhellig, J. A. Thomas,
J. Chem. Ecol. 1992, 18, 197.
[3] D. H. Netzly, L. G. Butler, Crop Sci. 1986, 26, 775.
[4] F. A. Einhellig, I. F. Souza, J. Chem. Ecol. 1992, 18, 1.
[5] F. A. Einhellig, J. A. Rasmussen, A. M. Hejl, I. F. Souza,
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[6] C. I. Nimbal, J. F. Pedersen, C. N. Yerkes, L. A. Weston,
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Trans 1 1990, 5, 1429.
2-Methoxy-6-[(octyloxy)methyl]benzo-1,4-quinone (18)
As described above in the synthesis of (16), the reaction of (15)
(389 mg, 1.38 mmol) and chromic anhydride (353 mg, 3.46 mmol)
afforded (18) as yellow crystals (94 mg, 24% yield). mp 44.8–45.9◦C.
νmax (KBr)/cm−1 2927, 2854, 1678, 1653, 1604, 1465, 1354, 1314,
1233, 1183, 1127, 1052, 906. δH (300 MHz) 0.88 (t, J 7.2, CH3), 1.21–
1.40 (m, 5 × CH2), 1.57–1.68 (m, H3ꢀ), 3.53 (t, J 6.6, H2ꢀ), 3.82 (s,
OCH3), 4.35 (d, J 2.1, H1ꢀ), 5.90 (d, J 2.4, H3), 6.76 (q, J 2.4, H5). δC
(75 MHz) 14.1 (C9ꢀ), 22.6 (C8ꢀ), 26.1 (C7ꢀ*), 29.2 (C4ꢀ*), 29.6, (C6ꢀ*),
29.7 (C5ꢀ*), 31.8 (C3ꢀ*), 56.3 (OCH3), 65.7 (C2ꢀ), 71.7 (C1ꢀ), 107.3
(C3), 132.0 (C5), 144.0 (C6), 158.6 (C2), 181.6 (C4), 187.4 (C1). * The
assignments could be inverted. m/z 168 (40%), 152 (30), 124 (35), 95
(30), 69 (80), 55 (100), 56 (60).
[8] J. M. L. Vanderlei, F. Coelho, W. P. Almeida, Tetrahedron 1997,
8, 2781.
[9] S. Poigny, M. Guyot, M. Samadi, Tetrahedron 1998, 54, 14791.
[10] T. M. L. Barbosa, F. A. Ferreira, L. C. A. Barbosa, I. F. Souza,
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Chemicals, 3rd ed. 1988, p. 340 (Pergamon: Oxford).
[12] A. Andreão, M. Sc. Thesis 1998 (Universidade Federal de Viçosa:
Viçosa).
Bioassays
The experiments were carried out in a greenhouse with Cucumis sativus,
Brachiaria decumbens, Hyptis lophanta, and Euphorbia heterophylla.
The bioassays for herbicide activity were carried out for quinones (1),
(9), (11), (12), and (16)–(18) using plastic pots, and the total growth of
the test plants evaluated.
The test solution was prepared by dissolving 5.0 mg of each quinone
in a mixture of xylene (60 µL), pentan-3-one (20 µL), and Tween 40
(2 drops). The volume of the resulting mixture was diluted to 100 mL
with distilled water.[11] A solution with the same composition described
above, but without the test compound, was used as a control.
[13] A. J. Mancuso, S. L. Huang, D. Swern, J. Org. Chem. 1978,
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[14] A. Andreão, L. C. A. Barbosa, A. J. Demuner, D. P. Veloso,
Abstr. 12th Encontro Regional 1998 (Sociedade Brasileira de
Química: Ouro Preto).
To plastic pots, of 0.10 dm3 volume containing 165 g of washed sand
soaked in 20 mL of the test solution, ten seeds of each test plant were
placed at 0.5–1.0 cm depth. The pots were kept in a greenhouse at 25◦C,
watered regularly to maintain the humidity at 12% w/w, and, three times
a week, a solution containing the required nutrients was applied.
The test plants Cucumis sativus, Brachiaria decumbens, and Euphor-
bia heterophylla were harvested 15 days after sowing. Hyptis lophanta
was harvested 20 days after sowing. The harvest was done by separa-
ting the radicle from the aerial parts. These parts were kept separately
in paper bags and dried at 75◦C until constant weight and the mass of
the dried matter determined. The data were analyzed using Tukey’s test
at 0.05 probability levels. All treatments were replicated six times in a
completely randomized design. The percentage of roots and aerial parts
growth inhibition were calculated in relation to the mass of the roots
and aerial parts growth inhibition of the control, respectively.
[15] C. K. Lau, C. Dufresne, P. C. Belanger, S. Pietri, J. Scheigetz,
J. Org. Chem. 1986, 51, 3038.
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52, 5574.
[18] W. M. MacLamore, J. Am. Chem. Soc. 1951, 73, 2221.
[19] W. P. Almeida, C. R. D. Correia, Tetrahedron Lett. 1994, 35,
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[20] L. H. B. Baptistella, J. F. Santos, K. C. Ballabio, A. J. Marsaioli,
Synthesis 1989, 436.
[21] S. F. Vaughn, G. F. Spencer, Weed Sci. 1996, 44, 7.