Synthesis and herbicidal activity of 2α,4α-dimethyl-8- oxabicyclo[3.2.1]oct-6-en-3-one derivatives

Article abstract of DOI:10.1021/jf990257k

The catalytic oxidation of 2α,4α-dimethyl-8-oxabicyclo[3.2.1]oct-6-en- 3-one with osmium tetraoxide and excess hydrogen peroxide resulted in the formation of 2α,4α-dimethyl-6,7-exo-isopropylidenedioxy-8- oxabicyclo[3.2.1]octan-3-one (2), with 91% yield. Addition of aryllithium reagents to this compound resulted in the formation of the aromatic alcohols (6a-h) with 48-76% yield. These alcohols were treated with thionyl chloride in pyridine, and the corresponding alkenes (7a-h) were obtained with 46-80% yield. The effect of compounds 6a-h and 7a-h on the root growth of Sorghum bicolor was evaluated at a concentration of 6.6 μg g^-1. The alcohols 6a-h caused an inhibitory effect (8-100%) on the S. bicolor radicle growth. The three most active compounds were 6e (aryl = p-methylphenyl), 6g (aryl = p- chlorophenyl), and 6h (aryl = p-fluorophenyl) and caused 100% inhibition. The effect of alkenes 7a-h was less pronounced and varied from 15% to 46% inhibition. Another experiment was carried out in a greenhouse to evaluate the effect of alcohols 6e, 6g, and 6h, at a 6.6 μg g^-1 dose, against Cucumis sativus, S. bicolor and the weeds Bidens pilosa, Desmodium tortuosum, and Pennisetum setosum. All three compounds showed an inhibitory effect on the development of the aerial parts (26-73%) and roots (13-79%) of the weeds and crops.

Full text of DOI:10.1021/jf990257k

J. Agric. Food Chem. 1999, 47, 4807−4814
4807
Syn th esis a n d Her bicid a l Activity of
2r,4r-Dim eth yl-8-oxa bicyclo[3.2.1]oct-6-en -3-on e Der iva tives†
Adilson V. Costa,‡ Luiz Cla´udio de A. Barbosa,*,‡ Antonio J . Demuner,‡ and Antonio A. Silva§
Laborato´rio de Ana´lise e S´ıntese de Agroqu´ımicos (LASA), Departamento de Qu´ımica, Universidade Federal
de Vic¸osa, 36571-000 Vic¸osa-MG, Brazil, and Departamento de Fitotecnia, Universidade Federal de Vic¸osa,
36571-000 Vic¸osa-MG, Brazil
The catalytic oxidation of 2R,4R-dimethyl-8-oxabicyclo[3.2.1]oct-6-en-3-one with osmium tetraoxide
and excess hydrogen peroxide resulted in the formation of 2R,4R-dimethyl-6,7-exo-isopropylidene-
dioxy-8-oxabicyclo[3.2.1]octan-3-one (2), with 91% yield. Addition of aryllithium reagents to this
compound resulted in the formation of the aromatic alcohols (6a -h ) with 48-76% yield. These
alcohols were treated with thionyl chloride in pyridine, and the corresponding alkenes (7a -h ) were
obtained with 46-80% yield. The effect of compounds 6a -h and 7a -h on the root growth of Sorghum
bicolor was evaluated at a concentration of 6.6 µg g-1. The alcohols 6a -h caused an inhibitory
effect (8-100%) on the S. bicolor radicle growth. The three most active compounds were 6e (aryl )
p-methylphenyl), 6g (aryl ) p-chlorophenyl), and 6h (aryl ) p-fluorophenyl) and caused 100%
inhibition. The effect of alkenes 7a -h was less pronounced and varied from 15% to 46% inhibition.
Another experiment was carried out in a greenhouse to evaluate the effect of alcohols 6e, 6g, and
6h , at a 6.6 µg g-1 dose, against Cucumis sativus, S. bicolor and the weeds Bidens pilosa, Desmodium
tortuosum, and Pennisetum setosum. All three compounds showed an inhibitory effect on the
development of the aerial parts (26-73%) and roots (13-79%) of the weeds and crops.
Keyw or d s: [3 + 4] cycloaddition; herbicides; plant growth regulators; weeds
INTRODUCTION
Since the discovery, in 1946, of the herbicide 2,4-
dichlorophenoxyacetic acid (2,4-D), the agrochemical
industry has successfully developed a wide array of
selective herbicides (Tomlin, 1994). Despite the reported
environmental and ecological problems caused by the
herbicides and also by other crop protection agents, they
continue to be used and are largely responsible for the
increasing food production (Best and Ruthven, 1995;
Klassen, 1995).
A major problem associated with the use of herbicides
is the occurrence of herbicide-resistant weeds (J asieniuk
et al., 1996). The 1995-1996 International Survey of
Herbicide-Resistant Weeds recorded 183 herbicide-
resistant weed biotypes in 42 countries (Heap, 1997).
As a consequence of this phenomenon, there is a
continuous need for the development of new products
with a new mode of action.
F igu r e 1. Generic structures for the new class of herbicidal
heterocyclic compounds.
influence the biological activity. For example, compound
1, having X) m-methyl, at a dose of 6.6 µg g-1, caused
100% mortality of the two important weeds Desmodium
tortuosum and Pennisetum setosum (Conceic¸a˜o, 1995),
while X)p-NMe2 had no effect on the same plants.
In this work, we describe the results of the prepara-
tion (Scheme 1) and biological activity of a new series
of compounds, having the general structure (7), derived
from the oxabicyclooctenone (2).
We have been involved in a research program directed
toward the development of new herbicides and plant
growth regulatory compounds, derived from the easily
available 8-oxabicyclo[3.2.1]oct-6-en-3-one (2) (Barbosa
et al.,1993; Barbosa et al.,1997; Demuner et al., 1998).
We have discovered that compounds having the
general structure 3-aryl-6,7-exo-isopropylidenedioxy-8-
oxabicyclo[3.2.1]oct-2-ene (1) (Figure 1) exibit a strong
herbicidal activity against several crops and weeds. The
substitution pattern of the aromatic ring was shown to
MATERIALS AND METHODS
Exp er im en ta l Ch em istr y. All melting points were ob-
tained with an Electrothermal digital apparatus and were
corrected. Infrared spectra were measured on a FTIR 3000
Mattson Instruments using a potassium bromide disk or a
sodium chloride liquid film cell, scanning from 625 to 4000
cm-1. Mass spectra were recorded under electron-impact (70
eV) or chemical ionization (NH3) conditions using a VG
1
ANALYTICAL ZAB-IF high-resolution spectrometer. H and
13C NMR spectra, respectively, were recorded on a J EOL
EX400 (400 and 100.53 MHz) spectrometer, using tetrameth-
ylsilane (TMS) as internal standard. Coupling constants (J )
are given in Hertz. Rf’s were determined by thin-layer chro-
matography on a 0.25 mm film of silica gel containing the
* To whom correspondence should be addressed. E-mail:
lcab@mail.ufv.br.
† Taken from the MSc dissertation of A.V.C.
‡ Departamento de Qu´ımica.
UV254 fluorescent indicator supported on
(Camlab plc.). Chromatographic purification were carried out
a plastic sheet
§ Departamento de Fitotecnia.
10.1021/jf990257k CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/12/1999

4808 J. Agric. Food Chem., Vol. 47, No. 11, 1999
Costa et al.
Sch em e 1
using silica gel (63-230 µm). Reagents and the solvents used
were purified according to the procedures described by Perrin
and Armarego (1988).
2r,4r-Dim e t h yl-6,7-exo-isop r op ylid e n e d ioxy-8-oxa -
bicyclo[3.2.1]octa n -3-on e (5).To a stirred solution of 2R,4R-
dimethyl-8-oxabicyclo[3.2.1]octan-3-one 2 (14.0 g, 92.1 mmol)
in acetone (60 mL) and diethyl ether (10 mL) was added a
solution of osmium tetraoxide (2.5% w/w in tert-butyl alcohol,
3.0 mL, 0.24 mmol), followed by hydrogen peroxide (30%, 10
mL, 88 mmol). A cloudy brown suspension was produced, and
this was stirred, in the dark, at room temperature for 72 h.
After this period of time the mixture had changed to a chalky
white appearance, and TLC analysis showed that all starting
material had been consumed. In a few occasions when the
reaction was repeated, a white solid was formed in variable
amounts (0-9%), and it was then removed by filtration and
identified as the dimer 4. The reaction was then quenched by
addition of Na2S2O3(s) until complete decomposition of the
excess of the hydrogen peroxide. After filtration, the solvent
was removed under reduced pressure to yield a viscous clear
oil. This oil was dissolved in dry acetone (70 mL), and to the
resultant solution were added p-toluenesulfonic acid (0.08 g)
and anhydrous CuSO4 (5 g). After the solution was stirred at
room temperature for 4 days, the solid material was removed
by filtration and NaHCO3 was added to the resultant solution
to neutralize the acid. The solvent was then removed under
reduced pressure, and the white solid obtained was purified
by flash column chromatography (hexane/diethyl ether 2:1) to
give 91% yield (18.9 g, 83.8 mmol) of the required product 3:
mp 86-88 °C; IR (KBr, cm-1) νjm a x 3400, 2990, 2930, 1710,
Syn th esis. 2,4-Dibr om op en ta n -3-on e. A two-necked, 250
mL flask was fitted with an overhead stirrer, a dropping
funnel, and a condenser. Bromine (20 mL, 62.04 g, 338 mmol)
was added dropwise to a stirred ice-cooled solution of pentan-
3-one (20 mL, 198 mmol) and phosphorus tribromide (1 mL,
2.85 g, 10 mmol). After complete addition of bromine, the
reaction was allowed to warm to 5-10 °C and stirred for an
additional 16 h. The flask was then evacuated with a water
pump to remove the dissolved hydrogen bromide, and the
resultant blue solution formed was distilled under reduced
pressure to yield (43.4 g, 178 mmol) 89.9% of the required
bromopentanone as a pale yellow oil: IR (film, cm-1) νjm a x 2980,
2900, 1725, 1464, 1340, 1190, 940, 850; 1H NMR (CDCl3) δ
1.90 (d, 6H, J ) 7.0, 2 × CH3), 5.10 (q, 2 H, J ) 7.0, 2 × CHBr).
2r,4r-Dim eth yl-8-oxa bicyclo[3.2.1]oct-6-en -3-on e (2). A
1 L two-necked round-bottom flask was fitted with a 100 mL
dropping funnel, and dry acetonitrile (200 mL) was added. Dry
NaI (90 g, 0.6 mol) was added with vigorous stirring under a
slow stream of nitrogen. Then powdered copper (20 g, 0.314
mmol) was added, followed by furan (30 mL, 0.4 mol). A
solution of 2,4-dibromopentan-3-one (29.04 g, 0.12 mol) in dry
acetonitrile (50 mL) was added, by means of a dropping funnel,
during 50 min, at 0 °C. The reaction mixture was allowed to
warm to room temperature and stirred for an additional 12 h.
After that time, the flask was cooled to 0 °C, and dichlo-
romethane (150 mL) was added. The resultant mixture was
then poured into a conical flask containing water (500 mL)
and crushed ice (500 mL) and thoroughly stirred to allow the
precipitation of copper salts. After filtration through a Celite
pad, the mother liquor was washed with aqueous NH3 solution
(45% v/v, 3 × 20 mL) and brine (20 mL), dried over MgSO4,
and concentrated under reduced pressure to leave a pale yellow
oil. Purification by flash chromatography (2:1 petroleum ether/
ether) gave 66.9% (12.2 g, 80 mmol) overall yield of the
required product 2 as a pale yellow oil: IR (KBr, cm-1) νjm a x
3080, 2960, 2910, 1710, 1450, 1340, 1170, 1050, 945; 1H NMR
1
1390, 1275, 1230, 1205, 1175, 1080, 1050, 810, 680; H NMR
(CDCl3) δ 1.01 (d, 6H, J ) 7.0, 2RMe), 1.27 (s, 3H, CH3), 1.50
(s, 3H, CH3), 2.79 (dq, 2H, J 2,Me ) J 4,Me ) 7.0, J 2,1 ) J 4,5 ) 5.5,
H2 and H4), 4.37 (d, 2H, J 1,2 ) J 5,4 ) 5.5, H1 and H5), 4.39 (s,
2H, H6 e H7); 13C NMR (CDCl3) δ 208.43 (C3), 111.72 (CMe2),
85.34 (C6 and C7), 80.12 (C1 and C5), 48.32 (C2 and C4), 25.88
(Me), 24.47 (Me), 9.34 (Me).
Data for insoluble dimer byproduct 4: mp 250-253 °C; IR
(KBr, cm-1) νjm a x 3420, 3000, 2950, 2900, 1710, 1470, 1375,
1160, 1110, 1060, 1040, 950, 840, 810; 1H NMR (CDCl3) δ 1.03
(d, 3H, J ) 7.0, Me), 1.05 (d, 3H, J ) 7.0, Me), 2.72 (d, 1H,
J OH,7 ) 9.1, H8), 2.75-2.79 (m, 2H, H2 and H4), 3.69 (d, 1H,
J 6,7 ) 6.2, H6), 4.04 (dd, 1H, J 7,6 ) 6.2, J 7,OH ) 9.1, H7), 4.36
(d, 1H, J 1,2 ) 4.7, H1), 4.37 (d, 1H, J 5,4 ) 5.1, H5); 13C NMR
(CDCl3) δ 208.00 (C3), 89.09 (C6), 86.06 (C5), 80.32 (C1), 71.45
(CDCl3) δ 1.01 (d, 6H, J ) 7.0, 2RMe), 2.85 (q, 2H, J 2,Me
)
J 4,Me ) 7.0, H2 and H4), 4.80 (d, 2H, J 5,4 ) J 1,2 ) 5.5, H1 and
H5), 6.40 (s, 2H, H6 and H7).

Herbicidal 8-Oxabicyclo[3.2.1]oct-6-en-3-one Derivatives
J. Agric. Food Chem., Vol. 47, No. 11, 1999 4809
Ta ble 1. Syn th esized 2r,4r-Dim eth yl-8-
6H, J ) 7.3, 2 × Me), 1.38 (s, 3H, Me), 1.54 (s, 3H, Me), 1.68
(s, 1H, OH), 2.35 (dq, 2H, J 2,Me ) J 4,Me ) 7.2, J 2,1 ) J 4,5 ) 4.0,
H2 and H4), 2.35 (s, 3H, Ar-Me), 2.39 (m, 2H, H2 and H4),
4.12 (d, 2H, J 1,2 ) J 5,4 ) 4.5, H1 and H5), 5.07 (s, 2H, H6 and
H7), 7.07-7.23 (m, 4H, H-aromatic); 13C NMR (CDCl3) δ 144.88
(C1′), 137.80 (C3′), 128.05 (C5′), 125.52 (C4′), 125.52 (C2′),
121.96 (C6′), 111.03 (CMe2), 84,25 (C6 and C7), 80.63 (C1 and
C5), 76.70 (C3), 42.65 (C2 and 4), 26.19 (M), 24.64 (Me), 21.67
(Me-Ar), 962 (Me); MS m/z 303 ([M - 15]+,100), 243 (10), 225
(7), 197 (6), 173 (7), 148 (12), 133 (6), 119 (60), 112 (17), 105
(7), 91 (18), 83 (11), 43 (7).
oxa bicyclo[3.2.1]oct-6-en -3-on e Der iva tives
R1
R2
R3
compd
yield (%)
compd
yield (%)
H
H
Me
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
OMe
H
6a
6b
6c
6d
6e
6f
68
60
48
55
76
61
69
66
7a
7b
7c
7d
7e
7f
67
72
56
80
63
46
64
64
H
Me
NMe2
Cl
6g
6h
7g
7h
F
Data for 6e: mp 230-232 °C; IR (KBr, cm-1) νjm a x 3490,
2950, 2900,1580, 1490, 1400, 1340, 1200, 1080, 1050, 950, 850,
810, 750, 680; 1H NMR (CDCl3) δ 0.72 (d, 6H, J ) 7.3, 2xMe),
1.37 (s, 3H, Me), 1.52 (s, 3H, Me), 1.57 (s, 1H, OH), 2.33 (s,
3H, Ar-Me), 2.35 (dq, 2H, J 2,Me ) J 4,Me ) 7.3, J 2,1 ) J 4,5 ) 4.0,
H2 and H4), 4.10 (d, 2H, J 1,2 ) J 5,4 ) 4,0; H1 and H5), 5.06 (s,
2H, H6 and H7), 7.15 (d, 2H, J ) 8,0, H3′and H5′), 7.25 (d,
2H, J ) 8.0, H2′and H6′); 13C NMR (CDCl3) δ 141.89 (C1′),
136.54 (C4′), 128.93 (C3′ and C5′), 124.08 (C2′ and C6′), 111.01
(CMe2), 84.49 (C6 and C7), 84.27 (C1 and C5), 76.7 (C3), 42.65-
(C2 and C4), 26.18 (Me), 24.64 (Me), 20.90 (Ar-Me), 9.54 (Me);
MS, m/z 303 ([M - 15]+,57), 269 (13), 243 (8), 177 (23), 148
(17), 112 (28), 91 (24), 59 (6), 43 (33).
(C7), 48.70 (C2), 48.26 (C4), 9.36 (CH3), 9.21 (CH3); MS m/z
354.1566 (M+, C18H26O7 requires 354.1678, 5), 337 (24), 239
(87), 197 (100), 169 (38), 152 (28), 137 (20), 125 (35), 111 (21),
96 (40), 81 (26), 69 (18), 55 (12), 41 (17).
Typ ica l P r oced u r e for th e P r ep a r a tion of th e Alcoh ols
6a -h . To a round-bottom flask was added the aryl bromide
(4.7 mmol) in dry THF (40 mL), and the system was kept under
nitrogen atmosphere at -78 °C. To this solution was added
butyllithium (1.6 M solution in hexane, 5 mmol), and the
reaction mixture was stirred for 1 h before the addition of the
acetonide 5 (2.2 mmol in 5 mL of dry THF). The resultant
reaction mixture was allowed to warm to room temperature
and stirred for a further 12 h when it was quenched by
addition of water (20 mL). The product was extracted with
ethyl acetate (5 × 30 mL), and the combined organic extracts
were dried over MgSO4 and concentrated under reduced
pressure to give a white solid. This solid was purified by
column chromatography (hexane/diethyl ether 2:1) to produce
the required alcohols 6a -h . The yields for the reactions are
presented in Table 1.
Data for 6f: mp 227-229 °C; IR (KBr, cm-1) νjm a x 3510,
3400, 3010, 2990, 2950, 2880, 1640, 1610, 1450, 1370, 1090,
1
1050, 800, 860, 700; H NMR (CDCl3) δ 0.73 (d, 6H, J ) 7.2,
2 × Me), 1.37 (s, 3H, Me), 1.52 (s, 3H, Me), 1.62 (s, 1H, OH),
2.32 (dq, 2H, J 2,Me ) J 4,Me ) 7.2, J 2,1 ) J 4,5 ) 4.0, H2 and H4),
2.94 (s, 6H, NMe2), 4.09 (d, 2H, J 1,2 ) J 5,4 ) 4.4, H5 and H1),
5.06 (s, 2H, H6 and H7), 6.69 (d, 2H, J ) 8.9, H3′and H5′), 7.2
(d, 2H, J ) 8.9, H2′and H6′); 13C NMR (CDCl3) δ 149.29 (C4′),
132.47 (C2′ and C6′), 125,61 (C1′), 111.99 (C3′ and C5′), (CM2),
110.91, 84.34 (C6 and C7), 80.66 (C1 and C5), 76,70 (C3), 42.67
(C2 and C4), 40.47 (NMe2), 26.17 (Me), 24.61 (Me), 9.62 (Me);
MS, m/z 348 ([M + 1], 6), 347 (M+, 20), 329 (87), 271 (13), 242
(18), 214 (13), 177 (52), 148 (100), 121 (39), 69 (8), 43 (14).
Data for 6a : mp 198-200 °C; IR (KBr, cm-1) νjm a x 3490,
2985, 2850, 1500, 1440, 1400, 1360, 1280, 1200, 1160, 1100;
1H NMR (CDCl3) δ 0.73 (d, 6H, J ) 7.3, 2 × Me), 1.39 (s, 3H,
CH3), 1.54 (s, 3H, CH3), 1.66 (s, 1H, OH), 2.39 (dq, 2H, J 2,Me
J 4,Me ) 7.3, J 2,1 ) J 4,5 ) 4.0, H2 and H4), 4.13 (d, 2H, J 1,2
)
)
Data for 6g: mp 228-230 °C; IR (KBr, cm-1) νjm a x 3520,
J 5,4 ) 4.0, H1 and H5), 5.09 (s, 2H, H6 and H7), 7.28-7.37
(m, 5H-aromatic); 13C NMR (CDCl3) δ 144.88 (C1′), 128.23 (C3′
and C5′), 126.95 (C4′), 124.87 (C2′ and C6′), 111.06 (CMe2),
84.25 (C6 and C7), 80.63 (C1 and C5), 76.7 (C3), 42.65 (C2
and C4), 26.18 (Me), 24.63 (Me), 9.60 (Me); MS m/z 289 ([M -
15]+, 100), 229 (10), 211 (8), 176 (8), 159 (6), 134 (13), 105 (72),
77 (18), 43 (26).
3410, 3350, 3010, 2980, 2870, 1500, 1370, 1200, 1080, 1050,
1
950, 850, 800, 750, 680; H NMR (CDCl3) δ 0.74 (d, 6H, J )
7.2, 2 × Me), 1.39 (s, 3H, Me), 1.54 (s, 3H, Me), 1.61 (s, 1H,
OH), 2.34 (dq, 2H, J 2,Me ) J 4,Me ) 7.2, J 2,1 ) J 4,5 ) 4.0, H2 and
H4), 4.12 (d, 2H, J 1,2 ) J 5,4 ) 4.1, H1 and H5), 5.06 (s, 2H, H6
and H7), 7.28-7.34 (m, 4H, H-aromatic); 13C NMR (CDCl3) δ
143.56 (C1′), 132.93 (C4′), 128.40 (C3′and C5′), 126.47 (C2′ and
C6′), 111.20 (CMe2), 84.17 (C6 and C7), 80.57 (C1 and C5),
76.71 (C3), 42.65(C2 and C4), 26.21 (Me), 24.68 (Me), 9.51 (Me);
MS m/z 324 ([M+1], 17), 323 (M+; 100), 263 (13), 245 (6), 217
(7), 193 (8), 181 (11), 139 (60), 123 (13), 111 (17), 95 (10), 83
(14), 55 (6), 43 (33).
Data for 6b: mp 211-213 °C; IR (KBr, cm-1) νjm a x 3495,
3010, 2970, 2950, 2800, 1600, 1500, 1450, 1320, 1250, 1200,
1100, 1050, 820, 760, 700; 1H NMR (CDCl3) δ 0.71 (d, 6H, J )
7.2, 2xMe), 1.36 (s, 3H, Me), 1.51 (s, 3H, Me), 1.86 (s, 1H, OH),
2.32 (dq, 2H, J 2,Me ) J 4,Me)7.2, J 2,1 ) J 4,5 ) 4.0, H2 and H4),
3.78 (s, 3H, OMe), 4.09 (d, 2H, J 1,2 ) J 5,4 ) 4.0, H1 and H5),
5.06 (s, 2H, H6 and H7), 6.86 (d, 2H, J ) 8.9, H3′ and H5′),
7.26 (d, 2H, J ) 8.9, H2′and H6′); 13C NMR (CDCl3) δ 158.18
(C4′), 136.83 (C1′), 126.21 (C2′ and C6′), 113.41 (C3′and C5′),
110.87 (CMe2), 84.30 (C6 and C7), 80.42 (C1 and C5), 76.76
(C3), 55.19 (OMe), 42.77 (C2 and C4), 26.12 (Me), 29.65 (Me),
9.67 (Me); MS m/z 335 ([M + 1], 3), 334 (M+; 11), 276 (9), 259
(8), 206 (27), 193 (100), 181 (24), 164 (66), 147 (24), 135 (68),
123 (16), 112 (80), 97 (31), 83 (39), 69 (6), 55 (11), 43 (47).
Data for 6c: mp 195-197 °C; IR (KBr, cm-1) νjm a x 3490,
3010, 2980, 2950, 2890, 1480, 1370, 1220, 1080, 1050, 950, 680,
Data for 6h : mp 222-224 °C; IR (KBr, cm-1) νjm a x 3490,
2950, 2920, 1500, 1370, 1220, 1090, 1050, 800, 860, 960, 670;
1H NMR (CDCl3) δ 0.76 (d, 6H, J ) 7.0, 2xMe), 1.38 (s, 3H,
Me), 1.53 (s, 3H, Me), 1.67 (s, 1H, OH), 2.76 (dq, 2H, J 2,Me
J 4,Me ) 7.0, J 2,1 ) J 4,5 ) 4.0, H2 and H4), 4.10 (d, 2H, J 1,2
)
)
J 5,4 ) 4.1, H1 and H5), 5.04 (s, 2H, H6 and H7), 6.92-6.96
(m, 4H, H-aromatic); 13C NMR (CDCl3) δ 163.20 (C4′), 143.50
(C1′), 125.90 (C2′ and C6′), 116.96 (C3′ and C5′), 111.34 (CMe2),
84.15 (C6 and C7), 80.60 (C1 and C5), 76.70 (C3), 39.45(C2
and C4), 26.23 (Me), 24.70 (Me), 9.95 (Me); MS m/z 307 ([M -
15]+, 100), 247 (11), 205 (10), 201 (9), 163 (13), 152 (12), 123
(76), 111 (14), 109 (12), 83 (11), 43 (37), 41 (9).
1
740; H NMR (CDCl3) δ 0.73 (d, 6H, J ) 7.4, 2x Me), 1.39 (s,
3H, Me), 1.52 (s, 3H, Me), 1.65 (s, 1H, OH), 2.38 (s, 3H, Ar-
Me), 2.41 (dq, 2H, J 2,Me ) J 4,Me ) 7.2, J 2,1 ) J 4,5 ) 4.0, H2 and
H4), 4.11 (d, 2H, J 1,2 ) J 5,4 ) 4.7, H1 and H5), 5.09 (s, 2H, H6
and H7), 7,15-7,46 (m, 4H, H-aromatic); 13C NMR (CDCl3) δ
145.02 (C1′), 135.10 (C2′), 133.48 (C3′), 127.52 (C4′), 125.79
(C5′), 123.82 (C6′), 111.03 (CMe2), 84.25 (C6 and C7), 80.63
(C1 and C5), 76.70 (C3), 39.01 (C2 and C4), 26.29 (M), 24.68
(Me), 21.68 (Me-Ar), 9,63 (Me); MS m/z 303 ([M - 15]+,100),
269 (11), 243 (7), 197 (6), 173 (7), 148 (12), 133 (6), 119 (60),
112 (17), 91 (18), 43 (7).
Typ ica l P r oced u r e for th e Deh yd r a tion Rea ction a n d
P r ep a r a tion of Alk en es 7a -h . To a stirred solution of the
alcohol 6a -h (4 mmol) in dry pyridine (2 mL), kept at 0 °C,
was added thionyl chloride (1 mL), and the resultant solution
was stirred at 0 °C until TLC analysis revealed the complete
consumption of the starting material (this time varied from 2
to 12 h). The reaction was quenched by addition of aqueous
HCl solution (2 M) until complete neutralization of the
pyridine. The product was extracted with diethyl ether (3 ×
20 mL). The organic extracts were combined, washed with
brine (2 × 20 mL), dried over MgSO4, and concentrated under
reduced pressure to give the crude product as pale yellow solid.
Data for 6d : mp 188-190 °C; IR (KBr, cm-1) νjm a x 3450,
3000, 2990, 2950, 2850, 1590,1500 1440, 1320, 1260, 1200,
1100, 1050, 900, 800, 760, 700; 1H NMR (CDCl3) δ 0.74 (d,

4810 J. Agric. Food Chem., Vol. 47, No. 11, 1999
Costa et al.
This solid was purified by column chromatography (hexane/
diethyl ether 5:1) to yield the required alkenes (7a -h ) as a
white solids. The products were recrystalized with a mixture
of dichloromethane and hexane. The yields for these reactions
are presented in Table 1.
84.76 (C7), 84.71 (C6), 81.82 (C5), 80.57(C1), 35.50 (C4), 26.24
(Me), 24.93 (Me), 21.16 (Ar-Me), 16.75 (Me), 14.01 (Me); MS
m/z 301 ([M + 1], 16), 300 (M+, 80), 285 (25), 242 (13), 227
(24), 213 (100), 199 (35), 185 (55), 141 (16), 115 (22), 91 (23),
43 (34). Anal. Calcd for C19H24O3: C, 75.97; H, 8.05. Found:
C, 75.89; H, 7.98.
Data for 7a : mp 157-159 °C; IR (KBr, cm-1) νjm a x 2980,
2970, 2670, 1580, 1490, 1440, 1370, 1270, 1200, 1080, 1050,
810, 720, 680; 1H NMR (CDCl3) δ 0.75 (d, 3H, J Me,4 ) 7.4, Me),
1.38 (s, 3H, Me), 1.57 (s, 3H, Me), 1.58 (d,3H, J Me,4 ) 2.3, Me),
3.07 (m, 1H, H4), 4.27 (s, 1H, H1), 4.33 (d, 1H, J 5,4 ) 5.4, H5),
4.69 (d, 1H, J 6,7 ) 5.7, H6), 4.86 (d, 1H, J 7,6 ) 5.7, H7), 7.05
(d, 2H, J ) 7.9, H2′and H6′), 7.25 (t, H, J ) 7.9, H4′), 7.33 (t,
2H, J ) 7.9, H3′and H5′); 13C NMR (CDCl3) δ 138.64 (C1′),
135.46 (C3), 129.28 (C3′ and C5′), 128.47 (C4′), 128.13 (C2′
and C6′), 126.66 (C2), 112.10 (CMe2), 84.73 (C7), 84.28 (C6),
81.80 (C5), 80.57(C1), 35.53 (C4), 26.26 (Me), 24.94 (Me), 16.71
(Me), 13.95 (Me); MS m/z 287 ([M + 1], 16), 286 (M+, 98), 271
(35), 228 (11), 213 (16), 199 (100), 185 (35), 171 (29), 158 (10),
143 (18), 128 (18), 115 (24), 105 (8), 91 (16), 82 (9), 69 (6), 43
(23). Anal. Calcd for C18H22O3: C, 75.50; H, 7.74. Found: C,
75.47; H, 7.70.
Data for 7f: mp 191-193 °C; IR (KBr, cm-1) νjm a x 2970,
1
2920, 2870, 1460, 1370, 1200, 1070, 1040, 850, 950, 680; H
NMR (CDCl3) δ 0.73 (d, 3H, J Me,4 ) 7.4, Me), 1.36 (s, 3H, Me),
1.59 (s, 3H, Me), 1.60 (d, 3H, J Me,4 ) 2.3, Me), 2.95 (s, 6H,
NMe2), 3.01 (m, 1H, H4), 4.26 (s, 1H, H1), 4.33 (d, 1H, J 5,4
)
5.40, H5), 4.66 (d, 1H, J 6,7 ) 5.7, H6), 4.85 (d, 1H, J 7,6 ) 5.7,
H7), 6.68 (dm, 2H, J ) 8.7, H3′and H5′), 7,25 (dm, 2H, J )
8.7, H2′and H6′); 13C NMR (CDCl3) δ 150.10 (C4′), 129.32 (C3),
126.54 (C1′), 125.20 (C2′ and C6′), 120.02 (C2), 113.40 (C3′and
C5′), 111.29 (CMe), 84.73 (C7), 84.61 (C6), 81.67 (C5), 80.31
(C1), 40.4 (NMe2), 30.30 (C4), 26.02 (Me), 24.70 (Me), 16.65
(Me), 13.93 (Me); MS m/z 330 ([M + 1], 30), 329 (M+, 100),
314 (5), 271 (8), 254 (6), 243 (9), 242 (30), 228 (35), 213 (11),
174 (13), 148 (12), 82 (16), 57 (17), 43 (41). Anal. Calcd for
C20H27NO3: C, 72.92; H, 8.26; N, 3.98. Found: C, 72.87; H,
8.23; N, 4.03.
Data for 7b: mp 163-165 °C; IR (KBr, cm-1) νjm a x 2990,
1
2880, 1610, 1500, 1320, 1250, 1080, 1050, 810, 760, 650; H
Data for 7g: mp 165-167 °C; IR (KBr, cm-1) νjm a x 3050,
NMR (CDCl3) δ 0.74 (d, 3H, J Me,4 ) 7.4, Me), 1.35 (s, 3H, Me),
1.55 (s, 3H, Me), 1.57 (d,3H, J Me,4 ) 2.3, Me), 3.01 (m, 1H, H4),
3.79 (s, 3H, OCH3), 4.24 (s, 1H, H1), 4.30 (d, 1H, J 5,4 ) 5.4,
H5), 4.66 (d, 1H, J 6,7 ) 5.7, H6), 4.83 (d, 1H, J 7,6 ) 5.7, H7),
6.85 (dm, 2H, H3′and H5′), 6.95 (dm, 2H, H2′and H6′); 13C
NMR (CDCl3) δ 158.23 (C4′), 135.00 (C3), 130.90 (C1′), 129.53
(C2′ and C6′), 129.19 (C2), 113.50 (C3′ and C5′), 112.05 (CMe),
84.61 (C7), 81.53 (C6), 81.67 (C5), 80.40 (C1), 55.2 (OMe), 35.57
(C4), 26.24 (Me), 24.93 (Me), 16.77 (Me), 14.045 (Me); MS m/z
317 ([M + 1], 22), 316 (M+, 100), 301 (12), 258 (12), 243 (11),
229 (86), 215 (24), 201 (36), 175 (8), 158 (9), 135 (10), 128 (6),
121 (14), 91 (5), 43 (13). Anal. Calcd for C19H24O4: C, 72.13;
H, 7.65. Found: C, 71.91; H, 7.55.
1
2970, 2830, 1480, 1370, 1260, 1080, 1050, 880, 860; H NMR
(CDCl3) δ 0.74 (d, 3H, J Me,4 ) 7.4, Me), 1.36 (s, 3H, Me), 1.56
(s, 3H, Me), 1.57 (d, 3H, J Me,4 ) 2.3, Me), 3.03 (m, 1H, H4),
4.26 (s, 1H, H1), 4.32 (d, 1H, J 5,4 ) 5.5, H5), 4.66 (d, 2H, J 6,7
) 5.7, H6), 4.84 (d, 2H, J 7,6 ) 5.7, H7), 6.97 (dd, 2H, J ) 8.4,
H3′ and H5′), 7,30 (dd, 2H, J ) 8.4, H2′ and H6′); 13C NMR
(CDCl3) δ 137.03 (C1′), 134.44 (C4′), 132.57 (C3), 130.10 (C2),
129.87 (C3′ and C5′), 128.43 (C2′and C6′), 122.90 (C2), 111.30
(CMe2), 84.67 (C7), 84.59 (C6), 81.64 (C5), 80.55 (C1), 35.47
(C4), 26.26 (Me), 25.02 (Me), 16.60 (Me), 13.91 (Me); MS m/z
321 ([M + 1], 21), 320 (M+, 95), 305 (71), 262 (17), 247 (27),
233 (100), 205 (46), 181 (14), 141 (19), 115 (29), 82 (14), 57 (9),
43 (47). Anal. Calcd for C18H21ClO3: C, 67.39; H, 6.60. Found:
C, 67.05; H, 6.56.
Data for 7c: mp 118-120 °C; IR (KBr, cm-1) νjm a x 2950,
1
2820, 1480, 1370, 1210, 1040, 1080, 950, 870, 760; H NMR
Data for 7h : mp 161-162 °C; IR (KBr, cm-1) νjm a x 3020,
(CDCl3) δ 0.75(d, 3H, J Me,4 ) 7.4, Me), 1.39 (s, 3H, Me), 1.57
(s, 3H, Me), 1.58 (d,3H, J Me,4 ) 2.3, Me), 2.25 (s, 3H, Ar-Me),
3.05 (m, 1H, H4), 4.29 (s, 1H, H1), 4.32 (d, 1H, J 5,4 ) 5.4, H5),
4.67 (d, 2H, J 6,7 ) 5.7, H6), 4.89 (d, 2H, J 7,6 ) 5.7, H7), 6.75
(d, 1H, J ) 7.3, H6′), 7.19 (d, 1H, J ) 6.22, H4′), 7.12-7.73
(m, 3H, H-aromatic); 13C NMR (CDCl3) δ 138.59 (C1′), 137.65
(C3′), 135.50 (C3), 132.26 (C4), 127.98 (C5′), 127.38 (C2′),
122.08 (C2), 120.01 (C6′), 112.07 (CMe2), 84.75 (C7), 84.71 (C6),
81.78 (C5), 80.60 (C1), 35.54 (C4), 26.26 (Me), 24.94 (Me), 19.70
(Me), 16.75 (Me), 13.99 (Me); MS m/z 301 ([M + 1], 12), 300
(M+, 70), 285 (15), 242 (8), 213 (100), 199 (30), 141 (12), 128
(20), 91 (25), 43 (37). Anal. Calcd for C19H24O3: C, 75.97; H,
8.05. Found: C, 75.93; H, 7.95.
2950, 2920, 2850, 1580, 1500, 1360, 1230, 1070, 1040, 800, 850,
1
750; H NMR (CDCl3) δ 0.73(d, 3H, J Me,4 ) 7.4, Me), 1.36 (s,
3H, Me), 1.54 (s, 3H, Me), 1.55 (d, 3H, J Me,4 ) 2.3, Me), 3.01
(m, 1H, H4), 4.25 (s, 1H, H1), 4.31 (d, 1H, J 5,4 ) 5.5, H5), 4.65
(d, 2H, J 6,7 ) 5.9, H6), 4.83 (d, 2H, J 7,6 ) 5.9, H7), 6.98-7.26
(m, 4H, H-aromatic); 13C NMR (CDCl3) δ 163.40 (C4′), 134.53
(C1′), 133.42 (C3), 129.50 (C2′ and C6′), 123.15 (C2), 115.30
(C3′ and C5′), 112.42 (CMe2), 84.65 (C7), 84.47 (C6), 81.75 (C5),
80.52 (C1), 35.57 (C4), 26.22 (Me), 24.93 (Me), 16.70 (Me), 13.94
(Me); MS, m/z 305 ([M + 1], 14), 304 (M+, 65), 289 (61), 246
(15), 217 (100), 203 (39), 189 (67), 133 (24), 109 (28), 82 (16),
57 (17), 43 (41). Anal. Calcd for C18H21FO3: C, 71.03; H, 6.95.
Found: C, 70.80; H, 6.85.
Data for 7d : mp 138-140 °C; IR (KBr, cm-1) νjm a x 2980,
1
Bioa ssa ys. Two different bioassays were carried out to
evaluate the plant growth regulatory activity of the synthe-
sized compounds. In all cases, a stock solution was prepared
dissolving each compound (50 mg) in xylene (3 mL). To this
solution were added sodium dodecyl sulfate (0.12 g), the
surfactant Tween 40 (0.7 mL), and water (10 mL). The
resultant suspension was sonicated for 3 min and then
transferred to a volumetric flask (1 L), and the volumewas
completed with water. A solution with the same composition
described above, but without the compound to be tested, was
used as a control.
Assa y of Root Elon ga tion in P etr i Dish es. Groups of
eight pregerminated Sorghum bicolor L. cv. BR007B were
placed in Petri dishes (i.d. ) 9 cm) containing washed sand
(150 g) and the solution (20 mL) containing the compound to
be tested. The Petri dishes were sealed with Parafilm and
incubated at 28 °C, in darkness, and at 75 °C. After 48 h, the
root length was measured to the nearest millimeter. All
treatments were replicated six times in a completely random-
ized design. The percentage of root growth inhibition was
calculated in relation to the root length of the control that was
5.98 cm. The data were analyzed using Tukey’s test at 0.05
probability level (Gomes, 1990).
2850, 1600, 1480, 1370, 1260, 1080, 1050, 850, 760, 700.; H
NMR (CDCl3) δ 0.70 (d, 3H, J Me,4 ) 7.4, Me), 1.29 (s, 3H, Me),
1.47 (s, 3H, Me), 1.48 (d,3H, J Me,4 ) 2.3, Me), 2.26 (s, 3H, Ar-
Me), 2.99 (m, 1H, H4), 4.18 (s, 1H, H1), 4.24 (d, 1H, J 5,4 ) 5.0,
H5), 4.60 (d, 2H, J 6,7 ) 5.8, H6), 4.78 (d, 2H, J 7,6 ) 5.8, H7),
6.75 (d, 1H, J ) 7.3, H6′), 7.12 (d, 1H, J ) 7.8, H4′), 7.14 (s,
1H, H2′), 7.22 (t, 1H, J ) 7.5, H5′); 13C NMR (CDCl3) δ 138.58
(C1′), 137.65 (C3′), 135.55 (C3), 129.05 (C4), 127.98 (C5′),
127.38 (C2′), 125.55 (C2), 123.32 (C6′), 112.07 (CMe2), 84.72
(C7), 84.71 (C6), 81.78 (C5), 80.56 (C1), 35.44 (C4), 26.26 (Me),
24.95 (Me), 21.45 (Me), 16.75 (Me), 13.99 (Me); MS m/z 301
([M + 1], 17), 300 (M+, 74), 285 (19), 242 (10), 213 (100), 199
(40), 128 (26), 91 (28), 43 (41). Anal. Calcd for C19H24O3: C.
75.97; H, 8.05. Found: C, 75.90; H, 8.01.
Data for 7e: mp 180-183 °C; IR (KBr, cm-1) νjm a x 3100,
1
2990, 1600, 1450, 1370, 1200, 1100, 850; H NMR (CDCl3) δ
0.75 (d, 3H, J Me,4 ) 7.4, Me), 1.36 (s, 3H, Me), 1.55 (s, 3H, Me),
1.58 (d,3H, J Me,4 ) 2.3, Me), 2.33 (s, 3H, Ar-Me), 3.04 (m, 1H,
H4), 4.25 (s, 1H, H1), 4.30 (d, 1H, J 5,4 ) 5.4, H5), 4.66 (d, 1H,
J 6,7 ) 5.5, H6), 4.84 (d, 1H, J 7,6 ) 5.5, H7), 6.91 (d, 2H, J )
8.0, H3′ and H5′), 7.21 (d, 2H, J ) 8,0, H2′ and H6′); 13C NMR
(CDCl3) δ 136.23 (C4′), 135.58 (C1′), 134.35 (C3), 128.80 (C3′
and C5′), 124.70 (C2′ and C6′), 122.24 (C2), 112.05 (CMe2),

Herbicidal 8-Oxabicyclo[3.2.1]oct-6-en-3-one Derivatives
J. Agric. Food Chem., Vol. 47, No. 11, 1999 4811
Ta ble 2. Effect of th e Alcoh ols 6a -h , a t 6.6 µg g-1, on th e
Ra d icle Gr ow th of S. bicolor L. a fter 2 Da ys In cu ba tion
a t 25 °C
compd
radicle lengtha (cm)
inhibition (%)
control
6b
6f
6c
6d
6a
6e
6g
6h
5.98a
0
8
7
8
8
22
100
100
100
5.48a,b
5.58a,b
5.51a,b
5.51a,b
4.66b
0.00c
0.00c
0.00c
F igu r e 2. Structure of the diol isolated from the oxidation
reaction of compound (2).
Gr een h ou se Exp er im en ts w ith S. bicolor , Cu cu m is
sa tivu s, a n d Weed s Bid en s pilosa , Desm od iu m tor tu o-
su m , a n d P en n isetu m setosu m . To each 0.35 L plastic pot
was added washed sand, which was then saturated with the
solution of the test compound (60 mL/450 g of sand, corre-
sponding to 6.6 µg at a.i./g substrate). Six seeds of each test
plant were placed in each pot. The pots were kept in a
greenhouse, watered regularly to mantain the humidity at
13.3% w/w, and three times a week, a solution containing the
required nutrients was applied. Fourteen days after sowing
the plants were harvested and the roots and aerial parts
separated and weighed. They were then dried at 72 °C, until
constant weight and the mass of the dried matter determined.
The percentage of root and aerial part growth inhibition was
calculated in relation to the mass of the control, respectively.
For S. bicolor and C. sativus, an experiment using soil as
substrate was carried out, and the results presented in
Table 5.
CV (%)
11.41
a
Means, in the same column, with the same letter are not
significantly different at P ) 0.05% by Tukey’s test.
Ta ble 3. Effect of th e Alk en es 7a -h , a t 6.6 µg g-1, on th e
Ra d icle Gr ow th of S. bicolor L. a fter 2 Da ys In cu ba tion
a t 25 °C
compd
radicle lengtha (cm)
inhibition (%)
control
7h
7b
7e
7c
7f
7a
7g
7d
5.00a
0
15
28
32
35
35
36
37
46
4.25a,b
3.60b,c
3.40b,c
3.25c
3.25c
3.18c
3.15c
2.71c
13.29
The data were analyzed using Tukey’s test at 0.05 prob-
ability level (Gomes, 1990).
CV (%)
a
Means, in the same column, with the same letter are not
RESULTS AND DISCUSSION
significantly different at P ) 0.05% by Tukey’s test.
Syn th esis. The [3 + 4] cycloaddition between the
oxyallyl cation generated from the ketone 2,4-dibro-
mopentan-3-one and furan resulted in the formation of
the required cycloadduct 2 in 66.9% yield (Aschroft and
Hoffmann, 1978). This reaction was carried out on a 0.1
mol scale and allowed for the preparation of several
grams (∼30 g) of the required starting material 2
(Scheme 1).
The oxidation of alkene 2 was carried out, at room
temperature, using excess hydrogen peroxide and a
catalytic amount of osmium tetraoxide (Schro¨der, 1980).
The end of the oxidation was visualized when the
reaction mixture changed to colorless. This oxidation
was repeated several times, and in a few cases, a
formation of a white solid was observed. This solid (4)
(Figure 2) was removed by filtration and the crude diol
3 was then converted in 90-98% yield into the acetonide
5.
with the Grignard reagent phenylmagnesium bromide,
but the required product 6a was obtained in only 30%
yield. The same Grignard methodology (Baker et al.,
1991) was used for the preparation of 6b, which was
isolated with only 24% yield. In both cases, a TLC
analysis of the reaction mixture revealed the formation
of several side products, as observed by Conceic¸a˜o (1995)
in a similar reaction. An alternative methodology in-
volving the use of aryllithium, prepared in situ from
butyllithium and aryl bromide, was used and a much
better yield of compounds 6a (68%) and 6b (60%) was
resulted. This methodology was then applied for the
preparation of the aromatic alcohols 6c-h , with good
yield (48-76%). All compounds (6a -h ) were purified by
column chromatography and recrystallized using a
mixture of dichloromethane and hexane.
The IR spectrum of compound 5 showed a strong
absorption at 1710 cm-1 (ν CdO). Special features in
the 1H NMR spectrum are the singlets at δ 1.27 and
1.50, due to the gem-dimethyl groups. The 13C NMR
spectrum showed eight signals, and the presence of the
isopropylidenedioxy group was confirmed by the signals
at δ 111.72, 25.8 (CH3) and 9.34 (CH3).
The side product 4, formed with 0-9% yield, and had
its structure deduced by spectroscopic means. The IR
spectrum showed a very strong absorption at 3420 cm-1
due to a OH group, and another band at 1710 cm-1 for
the ketone. The molecular formula C18H26O7 was de-
rived from HRMS (m/z 354.1566). The 13C NMR spec-
trum showed eight signals, all in accordance with the
dimer structure. As far as we are aware, the formation
of this type of dimer during the oxidation of alkenes has
not been previously reported.
The characterization of the alcohols 6a -h was carried
out by spectroscopic means. In all cases, the IR spectra
showed a strong absorption around 3450-3520 cm-1
due to the OH group stretching and also strong bands
at approximately 1600, 1580 and 1500 cm-1 due to the
CdC stretching of the aromatic ring. Special features
1
in the H NMR spectra were the presence of the signals
at around δ 6.8-7.4, due to the aromatic rings. The
absorptions due to the aliphatic part of the molecules
were similar, as can be observed from the data pre-
sented in Materials and Methods. It should be pointed
out that for all alcohols (6a -h ) the resonances due to
H6 and H7 appeared as a singlet at δ 5.04-5.09. These
hydrogens were deshielded by approximately 0.6 ppm
when compared with the same hydrogens in ketone 5.
This deshilding effect is attributed to the presence of
the hydroxyl group at the endo face of the molecule, and
the formation of only this isomer is a consequence of
The ketone 5 was subsequently converted into several
aromatic alcohols (6a -h ). Initially, ketone 5 was treated

4812 J. Agric. Food Chem., Vol. 47, No. 11, 1999
Costa et al.
Ta ble 4. Effect of th e Alcoh ols 6e,g,h a t 6.6 µg g-1, on th e Develop m en t of C. sa tivu s L. a n d S. bicolor L. a fter 14 Da ys a t
25 °C, Usin g Sa n d a s Su bstr a te
C. sativus L.
S. bicolor L.
aerial
part (g)
inhibition
roots
(g)
inhibition
(%)
aerial
part (g)
inhibition
roots
(g)
inhibition
(%)
compd
(%)
(%)
control
6e
6g
6h
CV (%)
0.18aa
0.15b
0.12b,c
0.08d
0.038a
0.028b
0.015b
0.015c
20.54
0.180a
0.040b
0.020b
0.010c
11.15
0.700a
0.050a,b
0.040b
0.010c
20.16
21
37
58
26
60
61
78
89
94
29
43
86
15.76
a
Means, in the same column, with the same letter are not significantly different at P ) 0.05% by Tukey’s test.
Ta ble 5. Effect of th e Alcoh ols 6e,g,h a t 6.6 µg g-1, on th e Develop m en t of C. sa tivu s L. a n d S. bicolor L. a fter 14 Da ys a t
25 °C, Usin g Soil a s Su bstr a te
C. sativus L.
S. bicolor L.
aerial
part (g)
inhibition
roots
(g)
inhibition
(%)
aerial
part (g)
inhibition
roots
(g)
inhibition
(%)
compd
(%)
(%)
control
6g
6e
6h
CV (%)
0.46aa
0.45a,b
0.31c
0.35b,c
11.30
0.12a
0.14a
0.90a
0.09b
13.99
0.29a
0.28a
0.27a
0.04b
9.38
0.14a
0.12a
0.13a
0.01b
18.11
2
35
24
-17
9
18
3
7
86
14
7
86
a
Means, in the same column, with the same letter are not significantly different at P ) 0.05% by Tukey’s test.
Ta ble 6. P er cen ta ge of In h ibition on th e Develop m en t of
compounds (1), prepared by Conceic¸a˜o (1995), we de-
cided to evaluate the biological activity of the synthetic
intermediate alcohols 6a -h .
th e Aer ia l P a r t (AP ) a n d Roots (R) of D. tor tu osu m , B.
pilosa , a n d P . setosu m Ca u sed by Com p ou n d s 6e,g,h a fter
14 Da ys a t 25 °C, Ca lcu la ted in Com p a r ison w ith th e
Con tr ol
In a preliminary in vivo screening carried out on Petri
dishes the effect of compounds 6a -h and 7a -h , at 6.6
µg g-1, on the radicle growth of S. bicolor was evaluated,
according to the methodology proposed by Parker (1965).
The results are shown in Tables 2 and 3. The most
active alcohols were 6e (p-methyl), 6g (p-chloro), and
6h (p-fluoro) that caused 100% inhibition on the Sor-
ghum root development. The compounds having a
methyl group on the ortho position (6c) and meta
position (6d ) had no significant effect (8% inhibition)
on the sorghum development, indicating that the posi-
tion of the substituents is important, in this case, for
the biological activity.
The only alkene that did not cause any significant
effect on the development of S. bicolor was 7h (15%
inhibition). Although all the other alkenes caused a
significant inhibition on the sorghum root development,
this effect was small (28-46%) compared with the
alcohols 6e,g,h .
Considering the results obtained, the three most
prominent compounds (6e,g,h ) were submitted to a
greenhouse experiment, employing plastic flower pots
containing sand or soil as substrate.
The compounds were tested at the concentration of
6.6 µg g-1, initially against S. bicolor and C. sativus L.
From the results presented in Table 4 (sand as sub-
strate) all compounds had a significant inhibitory effect
on the development of the aerial part (21 to 58%) and
roots (26 to 61%) of C. sativus.
inhibition (%)
compd D. tortuosum
B. pilosa
P. setosum
AP
R
73
67
75
AP
41
55
57
R
64
61
79
AP
26
30
40
R
13
19
51
6e
6h
6g
63
73
73
the preferential attack of the nucleophile from the less
hindered face of the carbonyl group (Deslongchamps,
1989).
The dehydration of the alcohols was initially carried
out with concentrated HCl in acetone under reflux, but
the alkenes were obtained in very low yield (ex. 7a ,
24%). The low yield for these reaction could be associ-
ated with the partial hydrolysis of the acetonide (Madha-
van and Martin, 1986) moiety and also to the formation
of the compounds result from the substitution of the OH
group by chlorine (Ferreira, 1998).
Another dehydration procedure, using SOCl2 in py-
ridine (Bernstein and Allen, 1954), was used, and the
alkenes 7a -h were obtained in good yields (46-80%).
All compounds, after purification by column chroma-
tography, were recrystalized and obtained in a very pure
form for the biological assays.
The structure of the alkenes 7a -h were confirmed
by spectroscopic analysis.
The synthetic route developed allowed for the prepa-
ration of gram quantities of eight new alkenes derived
from the 2R,4R-dimethyl-8-oxabicyclo[3.2.1]oct-6-en-3-
one (2), in good yields.
Biologica l Activity. In the process of discovery of
new agrochemicals, the strategy that involves a random
screening of new chemicals is still used (Cobb, 1992;
Copping and Hewitt, 1998).
In this work, we initially planed to prepare several
aromatic alkenes to evaluate the influence of the
aromatic portion and also the presence of the methyl
groups at the 2 and 4 positions on the biological activity.
Although we do not know the mode of action of the
The compounds caused a greater inhibition on the
development of S. bicolor (aerial part 78-94%) and roots
29-86%), confirming the results previously obtained
from the assays carried out on Petri dishes (Table 2).
When soil was used as substrate, compounds 6e and
6g caused a small effect or had no influence at all on
the development of S. bicolor and C. sativus. On the
other hand, 6h caused 24% and 18% inhibition on the
aerial parts and roots, respectively, of C. sativus, but
was very active against S. bicolor (86% inhibition on
the aerial parts and roots (Table 5).

Herbicidal 8-Oxabicyclo[3.2.1]oct-6-en-3-one Derivatives
J. Agric. Food Chem., Vol. 47, No. 11, 1999 4813
F igu r e 3. Comparison of aerial parts and root growth in S. bicolor. (a) From left to right: control, water, and plant treated with
6.6 µg g-1 of compound 6h , after 14 days at 25 °C using soil as substrate. (b) Detail showing the symptoms caused by compound
6h .
Although we have no information about the mode
of action of these compounds, a general reduction of
the plant growth was observed, and in all cases chlo-
rosis, followed by necrosis occurred as exemplified in
Figure 3.
The alcohols 6e, 6g, and 6h were also active against
the important weeds D. tortuosum, B. pilosa, and P.
setosum (Table 6). The less pronounced effect was
observed in the case of P. setosum (13-51% inhibition
on the aerial parts and roots).
In conclusion, we have demonstrated that the new
compound derivatives of 2R,4R-dimethyl-8-oxabicyclo-
[3.2.1]oct-6-en-3-one present relative herbicidal activity.
These compounds can be further modified in order to
increase the biological activity.
Future structural modification and biological evalu-

4814 J. Agric. Food Chem., Vol. 47, No. 11, 1999
Costa et al.
oxabiciclo[3.2.1]oct-2-eno (Synthesis and evaluation of the
herbicidal activity of 3-aryl-6,7-exo-isopropylidenedioxy-8-
oxabicyclo[3.2.1]oct-2-ene compounds). MS Thesis, Univer-
sity of Vic¸osa, 1995.
ation should be carried out in order to explore the full
potential of this new class of herbicidal molecules.
ACKNOWLEDGMENT
Copping, L. G.; Hewitt H. G. Chemistry and mode of action of
crop protection agents; RSC: London, 1998.
L.C.A.B. is very grateful to the Royal Society of
Chemistry for a Research Grant. We also thank the
following Brazilian agencies: Conselho Nacional de
Desenvolvimento Cient´ıfico e Tecnolo´gico (CNPq), for a
research fellowship (L.C.A.B.), a MSc studentship (A.V.C.)
and research grant, and Fundac¸a˜o de Amparo a` Pes-
quisa do Estado de Minas Gerais (FAPEMIG) for
financial support. We are also very grateful to Prof.
Francisco Affonso Ferreira from the Department of
Plant Science (UFV) for helping us with the biological
assays.
Demuner, A. J .; Barbosa, L. C. A.; Veloso D. P., New
8-oxabicyclo[3.2.1]oct-6-en-3-one Derivatives with Plant
Growth Regulatory Activity. J . Agric. Food Chem. 1998, 46,
1173-1176.
Deslongchamps, P. Stereoeletronics effects in organic chemistry;
Pergamon Press: Oxford, U.K. 1989.
Ferreira, M. L. S´ıntese e avaliac¸a˜o da atividade herbicida de
quinonas. MS Thesis, University of Vic¸osa, 1998.
Gomes, F. P. Curso de estat´ıstica experimental; 13th ed.;
Nobel: Piracicaba, 1990.
Heap, T. M. The occurrence of herbicide resistant weeds
worldwide. Pestic. Sci. 1997, 51, 235-243.
J asieniuk, M.; Bruˆle´-Babel, A. L. and Morrison, I. N. The
evolution and genetics of herbicide resistance in weeds.
Weed Sci. 1996, 44, 176-193.
Klassen, W. In World food security up to 2010 and global
pesticide situation; Ragsdak, N. M., Kearney, P. C., Plimmer,
J . R. Fifth international congress of pesticide chemistry;
ACS: Washington, DC, 1995.
Madhavan, G. V. B.; Martin, J . C. A Novel and Stereospecific
Synthesis of (()- and (-)-Aristeromycin. J . Org. Chem 1986,
51, 1287-1293.
Parker, C. A. Rapid bioassay method for the detection of
herbicides which inhibit photosynthesis. Weed Sci. 1965, 5,
181-184.
LITERATURE CITED
Aschroft, M. R.; Hoffmann, H. M. R. Org. Synth. 1978, 55, 17-
23.
Baker, K. Y.; Brown, J . M.; Hughs, N.; Skarnulis, A. J .; Sexton,
A. Mechanical action of magnesium turnings for the prepa-
ration of reactive Grignard reagent. J . Org. Chem. 1991,
56(2), 698-703.
Barbosa, L. C. A.; Demuner, A. J .; Borges, E. E. L.; Mann, J .
Synthesis and evaluation of the plant growth regulatory
activity of 8-oxabicyclo[3.2.1]oct-6-en-3-one derivatives. J .
Braz. Chem. Soc. 1997, 8, 19-27.
Barbosa, L. C. A.; Demuner, A. J .; Mann, J .; Pilo-Veloso, D.
Novel rearrangement of 2R-isopropyl-8-oxabicyclo[3.2.1]oct-
6-ene producing the monoterpene 3-hydroxyphellandral. J .
Chem. Soc., Perkin Trans. 1 1993, 585-587.
Bernstein, S.; Allen,W. S. Steroidal cyclic ketals. J . Org. Chem.
1954, 77, 1028-1033.
Best, G. A.; Ruthven, A. D. Pesticides: Development, impacts
and control; RSC: Cambridge, U.K., 1995.
Cobb, A. Herbicides and plant physiology; Chapman & Hall:
London, U.K., 1992.
Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory
Chemicals; Pergamon Press: Oxford, U.K., 1988.
Schro¨der, M. Osmium Tetroxide cis-Hydroxylation of Unsatur-
ated Substrates. Chem. Rev. 1980, 80, 187-213.
Tomlin, C. The pesticide manual; RSC: Cambridge, U.K., 1994.
Received for review March 16, 1999. Revised manuscript
received J uly 22, 1999. Accepted J uly 27, 1999.
Conceic¸a˜o, G. A. S´ıntese e avaliac¸a˜o da atividade herbicida
de compostos do tipo 3-aril-6,7-exo-isopropilidenodioxi-8-
J F990257K