Herbicidal Pyrazolyl Trifluorotoyl Ethers
J. Agric. Food Chem., Vol. 44, No. 11, 1996 3649
the herbicidal potential of this class of chemistry. In principle,
formamide at a rate just sufficient to sustain nitrogen evolu-
tion. The addition funnel was rinsed with 20 mL of dimeth-
ylformamide supplemented with 1 mL (7.6 mmol) of tert-butyl
nitrite. Once gas evolution was complete, the reaction mixture
was diluted to 4 L with ice water and 1 L of concentrated
hydrochloric acid. Products were recovered by repeated
extractions into ethyl ether, and the combined organic layers
were washed with saline 4 N hydrochloric acid and then saline
and dried with magnesium sulfate to afford 33 as 14 g of yellow
liquid (49% yield). A portion (0.56 g) was dried under vacuum
for elemental analysis and biological evaluation, yielding 0.48
g of oil, bp 70 °C at 9 torr (dec).
a
toluidine ether such as 11 could be converted to the
corresponding phenol or methyl ether via diazotization. In
practice, however, this compound is too electron deficient to
undergo such a reaction. Hence, diazotization goes poorly, and
reduced or polymeric products are obtained instead of the
desired oxy derivatives.
Instead, commercially available dihalobenzoic acids 36a and
36b were nitrated and the products were converted to the
corresponding benzotrifluorides 37a and 37b by treatment
with sulfur tetrafluoride in anhydrous hydrofluoric acid.
Coupling of these dihalo intermediates with hydroxypyrazoles
was unexpectedly complicated, however. In dimethyl sulfox-
ide, the desired heterologous diethers 38 and 39 were minor
components of the mixtures obtained. Rather, the predomi-
nant products found were bispyrazolyl- and bisalkoxy phen-
ylene diethers; the former were more prevalent for difluoro
37a , whereas the latter were prevalent when chlorofluoro 37b
was used as starting material. A more favorable product
distribution was observed in refluxing methanol, but losses
to side products were still considerable. When the first
displacement step was run at room temperature, however, it
was found that reaction to form 38 and 39 was both regio-
specific and quantitative.
3′-Chloro 39a and 39b proved unsuitable for further aro-
matic nucleophilic substitution, because the pyrazoloxy group
ortho to the activating nitro substituent is a better leaving
group than is the chloride at the respective para position.
Fluoro 38, on the other hand, reacted cleanly in methanol and
in ethanol to yield 40a and 40b, respectively. Thioether
oxidation, nitro reduction, and deamination were then applied
where appropriate as outlined in Scheme 1 to return 8, 16a ,
and 16b. Application of the same procedures to 3′-chloro 40a
and 40b afforded 1c, 6c, and 10c.
H3F4NO2 (209.11), expected: C, 40.21; H, 1.45; N, 6.70%.
C7
Found: C, 40.30; H, 1.46; N, 6.65%. NMR: 1H δ 7.66 (dd, J
) 8.8 and 5.0 Hz, C6H), 7.42 (dd, J ) 7.6 and 2.4 Hz, C3H),
and 7.24 (∼trd, J ) 6 and 2.6 Hz, C5H); 13C δ 164.3 (d, J )
270 Hz, C4F), 130.3 (m, C6H), 123.5, 119.7 (d, J ) 22 Hz), and
113.3 (d, J ) 27 Hz); 19F δ -60.8 (s, CF 3) and -103.4 (∼q, J
) 5.7 Hz).
4-Ch lor o-1-m eth yl-5-(m eth ylth io)-3-[3-n itr o-4-(tr iflu o-
r om eth yl)p h en oxy]p yr a zole (6d ). (Methylthio)hydroxy-
pyrazole 21 (4.3 g, 24 mmol) was slurried with potassium
carbonate (4 g, 30 mmol) in 50 mL of dimethyl sulfoxide, and
33 (5.0 g, 24 mmol) was added. The reaction flask was flushed
with nitrogen and stirred at 80 °C in an oil bath for 24 h, at
which point the reaction mixture was diluted into 5% aqueous
sodium bicarbonate and products were extracted into 1:1 ethyl
acetate/ether. The organic layer was washed twice with brine
and dried with magnesium sulfate. Recrystallization from
methylcyclohexane with a trace of ethyl acetate gave ether 6d
as beige crystals. C12H9ClF3N3O3S (367.74), expected: C,
39.19; H, 2.47; N, 11.43%. Found: C, 39.37; H, 2.49; N,
11.52%.
4-Ch lor o-1-m eth yl-5-m eth a n esu lfon yl-3-[3-n itr o-4-(tr i-
flu or om eth yl)p h en oxy]p yr a zole (10d ). A solution of thio-
ether 6d (1.0 g, 2.6 mmol) in 20 mL of dichloromethane was
cooled to 0 °C, and 3-chloroperbenzoic acid (1.5 g, 7 mmol) was
added. After 20 min at 0 °C, the flask was allowed to warm
to room temperature and stirred for 10 h. The mixture was
then quenched into 5% sodium thiosulfate and the organic
layer washed with saturated sodium bicarbonate and then
with brine. Solvent was evaporated under reduced pressure
and the crude product triturated with methylcyclohexane to
give sulfone 10d as a white powder. C12H9ClF3N3O5S (399.74),
expected: C, 36.06; H, 2.27; N, 10.51; S, 8.02%. Found: C,
36.48; H, 2.29; N, 10.25; S, 7.98%.
4-Ch lor o-1-m eth yl-5-m eth an esu lfon yl-3-[3-am in o-4-(tr i-
flu or om eth yl)p h en oxy]p yr a zole (11). Nitrotolyl ether 10d
(9.85 g, 25 mmol) was dissolved with heating in 75 mL of
glacial acetic acid diluted with 25 mL of water. Gradual
addition of iron powder (6 g, 0.11 mol) over 30 min gave a
vigorous exothermic reaction. After 30 min more at 80 °C,
the mixture was diluted into water and extracted twice with
ethyl ether after acidification with a few milliliters of hydro-
chloric acid. The pooled organic extracts were filtered through
Celite and dried with magnesium sulfate. Evaporation of
solvent gave toluidine ether 11 as a white powder in quantita-
tive yield. C12H11ClF3N3O3S (369.76), expected: C, 38.98; H,
3.00; N, 11.36%. Found: C, 39.27; H, 3.05; N, 11.23%.
4-Ch lor o-1-m eth yl-5-m eth a n esu lfon yl-3-[3-a ceta m id o-
4-(tr iflu or om eth yl)ph en oxy]pyr azole (12b). Toluidine ether
11 (2.2 g, 6 mmol) was taken up in 10 mL of acetic anhydride
and heated to 50 °C; an additional bolus of 10 mL of acetic
anhydride was added after 2 h to keep the mixture homoge-
neous. After 3 h at 50 °C, the mixture was diluted into water.
The product acetanilide 12b crystallized out of solution as a
white solid. C14H13ClF3N3O4S (411.79), expected: C, 40.83; H,
3.18; N, 10.20; S, 7.79%. Found: C, 40.90; H, 3.22; N, 10.26;
S, 7.79%.
DETAILED SYNTHESES
4-F lu or o-2-n itr oben zotr iflu or id e (33). Palladium cata-
lyst (10% on carbon, Matheson Coleman & Bell; 0.3 g) was
wet with ethanol. 3-Nitro-4-fluorobenzotrifluoride (22a ; 33 g,
0.16 mol) was added as a solution in 150 mL of additional
ethanol and the slurry pressurized to 50 psi overpressure on
a Parr hydrogenator. The cell was agitated and repressurized
twice over 15 h, and then the reaction mixture was filtered
through Celite and partitioned between 2:1 ethyl ether/ethyl
acetate and brine. The organic layer was dried with magne-
sium sulfate and the solvent evaporated to give the aniline as
a yellow oil. The aniline was added to 75 mL of acetic
anhydride contained in a flask fitted with a water-cooled
condenser; reflux was driven by the heat of reaction as the
aniline was added. After 3 h, the solution was poured into
750 mL of water and the anilide product 31 was collected by
filtration; yield was quantitative.
Nitric acid (71%; 150 mL) was cooled to 0 °C in a saltwater
ice bath, and chilled concentrated sulfuric acid (250 mL) was
added slowly. Once the nitration mixture had cooled back
below 5°C, acetanilide 31 (24.4 g, 0.14 mol) was added
gradually over 20 min. The mixture was then quenched into
350 g of ice water. Nitroacetanilide product 32 was recovered
by filtration as a pale yellow powder comprised of 2- and
4-nitro isomers in a 1:1 ratio.
The nitroacetanilide 32 were taken up in 200 mL of
methanol, 50 mL of 12 N hydrochloric acid was added, and
the mixture was heated to reflux for 1 h. After dilution into
water, crude nitroanilines were collected by filtration (20.4 g)
and additional product was recovered by extraction of the
filtrate with ethyl ether. After drying with magnesium sulfate
and evaporation of the solvent, the residual red oil (3.0 g) was
taken up in ethyl acetate and dried with magnesium sulfate
plus silica gel. Removal of solvent by rotary evaporation gave
27.3 g of isomeric fluoronitroanilines (90% overall yield).
Anhydrous dimethylformamide (300 mL) was heated to 65
°C in a dry flask fitted with a reflux condenser, and tert-butyl
nitrite (23 mL, 0.17 mol) was added. A portion of the
nitrotoluidine mixture (26.9 g, 0.12 mol) was then added
dropwise as a solution in 150 mL of anhydrous dimethyl-
BIOLOGY
Da ta Red u ction . Summary data for pre-emergent
herbicidal activities against warm season weeds are
given in Table 2. Fluorotolyl and fluoroanisole pyrazole
Clark, Robert D.
