CA1257296A - Fluorophenoxy -phenol and -benzeneamine intermediates for herbicides - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE

The invention relates to a compound of the formula wherein X represents -Cl, -Br, -CF3, -I, -OCF3, F, -CF2Cl, -CF2H
or -OCF2CCl2H or a salt thereof. These compounds are intermediates useful for preparing herbicides.

Description

~25729~ 4693-3474D

This application is divided out of p~rent ~pplication serial no. 462,134 ~iled August 30, 1984 and relates to intermediates useful in preparing the no~el herbicides which are the subject of the parent application.

The intermediates which are the subject of the present divisional application are compounds of the formulae X ~ ~ OH

and F
X~ O~NH2 wherein X is -Cl, -Br, -CF3, -I, -OCF3, -F, -CF2Cl, -CF2H or -OCF2CC12H, or salts thereo.

The invention of the parent application relates to:
novel fluorophenoxyphenoxypropionates and derivatives thereof (hereinafter also referred to as the "active ingredients") which are useful as herbicides; to herbicidal compositions containing these novel compounds; and to methods of using these compounds for the control of weeds in non-crop areas as well as in the presence of valuable crops.

.y~

~572~ 4693-3474D

Various 4-phenoxy-phenoxy-propionic acids are known as herbicidal agents. U.S. Patent 4,332,961 discloses 2-~4-(4-trifluoromethylphenoxy)phenoxy]alkane carboxylic acid and derivatives thereof wherein the "4-trifluoromethylphenoxy group"
may optionally contain a chloro substituent. U.S. Patent 4,332,960 discloses 2-14-(2-hydrogen or halogen-4-trifluoromethyl-phenoxy)--phenoxy]propionic acid and derivatives thereof wherein hydrogen is the preferred substituent at the 2' position. Both of these patents teach the compounds disclosed in them as possessing herbicidal activity.

U.S. Patent 4,370,489 discloses 2-[4-(2-chloro-4-bromo-phenoxy)-phenoxy]propionic acid and derivatives thereof as possessing herbicidal activity.

Heretofore, 2-[4-(2-fluoro-4-substituted-phenoxy)phenoxy]-propionic acids and agriculturally acceptable derivatives thereof have not been disclosed.

Agriculturally acceptable derivatives of the active ingredients include compounds of the formula:

X ~ O - ~ Z (II) wherein X represents ~Cl, -CF3, -I, -Br, -OCF3, F, -CF2Cl, -CF2H or -OCF2CC12H; and 1257~9~

z represents an organic moiety containing N, O or S atoms, a metallic cation, an ammonium cation, or an organic amine cation and is or can be hydrolized and/or oxidized in plants or soil to a carboxyl moiety that is in undissociated and/or dissociated form.
More particularly Z moieties are Rl -C- (Y) nR

wherein Y represents a saturated or unsaturated hydrocarbyl group containing an even number of carbon atoms, preferably from

2 to 18 carbon atoms;
n represents O or l;
R represents H or a Cl-C3 alkyl group; and R is a carboxyl group; an alkali metal, alkaline earth metal, ammonium or organic amine salt thereof; or an organic group containing N, O or S atoms that can be hydroly~ed and/or oxidized in plants or the soil to a carboxyl group that is in undissociated and/or dissociated form.
- The term "herbicide" is used herein to mean an active ingredient which controls or adversely modifies the growth of plants.
By "growth controlling" or "herbicidally-effective" amount is meant an amount of active ingredient which causes an adversely modifying effect and includes deviations from natural development, killing, regulation, dessication, retardation, and the like.
The term "plants", when used herein, is meant to include ~ ~ ~ q 2 9 6 4693-3474D

germinant seeds and emerging seedlings as well as established vegetation.
The term "halogen" when used herein is meant to include F, Cl, I an Br.
The term "agriculturally acceptable salts, amides and esters", when used to describe the active ingredients disclosed herein, is meant to encompass any salt, amide, ester or derivative of said active ingredients tacids) which (1) does not substantially affect the herbicidal activity of said active ingredients, or (2) is or can be hydrolyzed and/or oxidized in plants or soil to a carboxyl moiety that is in undissociated and/or dissociated form.
Preferably, R2 represents moieties corresponding to one of the following formulae:
(1) -CN;

(2~ -C~ ~ H

\N~N

H

(3) - ~ \ ~

(4) -C-Hal, wherein Hal is halogen;
o

(5) ~C~o M~, wherein M represents a metallic ~25;72~;

cation, ammonium cation or an organic amine cation, typically, but not exclusively, containing hydrocarbyl (saturated or unsaturated), alicyclic, heterocyclic or aromatic groups, all unsubstituted or substituted with various other groups not limited to, but including, halo, cyano, nitro and unsubstituted or substituted thiol, hydroxy, amino or carboxyl groups and, addition-ally, alicyclic, heterocyclic and aromatic groups substituted with unsubstituted or substituted saturated or unsaturated hydrocarbyl groups, for example, trifluoromethyl, chloromethyl, cyanomethyl and vinyl;

(6) -CH20R3;
o

(7) -C-R ;

2S729~ ~9 ( 8 ) -CH2O-C-R

( 9 ) -C-OR

( l 0 ) -C-SR3 ;

A R
( 11 ) -C-~
\R

/
15 ( 12 ) -CH2O-C-N~

A R
20 ( 13 ) -C-~

A ~3 ( 14 ) -C-N~
CN

A R
( 15 ) -CH2O-C-N~
CN

( 16 ) -C=N-R

31, 624-F -6-~25729~

( 1 7 ) - C=N-R3;

s:) H/hydrocarbyl ,., 3 5 ( 18 ) -C-NOR

(l9) -C N N\
R

"
10 (20) -C--N -N\
CN

"
(21 ) -C--N N

A R O
" ' " 3 ( 22 ~ -C N C R

~oR6 ( 23 ) ~C~ --oR6 ~R6 20 (24) -C(S~6)3 31, 624-F -7-`` ~2S7;29d~ '9 (25) -C(OR )2 (26) -C(SR )2 (27) fR~

-C-H

(28) S ~
~C~ ;

(29) ~ ~

o N(R ) "
(30) -C-N=C~
N(R )2 (31) ~ J
-CH

wherein W represents -OR , -SR or halogen;
A represents O or S;

31,624-F -8-. ~æs7~s~

R represents H or R ;
R4 represents H, alkoxy or R ;
R5 represents ~, a m~tallic cation or R6; and R6 represents a hydrocarbyl (saturated or unsaturated), alicyclic, heterocyclic or aromatic group, ~nsubstituted or substituted with various other groups not limited to, but including, halo, cyano, nitro and unsubstituted or substituted thiol, hydroxy, amino or carboxyl groups and, additionally, alicyclic, heterocyclic and aromatic groups substituted with unsubstituted or substituted saturated or unsaturated hydrocarbyl groups, for example, trifluoromethyl, chloromethyl, cyanomethyl and vinyl;

,, ~'~" 7 (32) -C-N R

A
- ~ 7 ~33) 2 ~ R
~R7 (34) -C=N-R3;

B R
(35) -C-N where s is O, S or N; or ,, , ~ 7 (36) -C - N -N R , where R7 completes an unsubstituted or substituted heterocyclic ring system and A represents O or S.

31,624-F -9-.~ ;2S7296 4693-3~7~D
R is preferably a carboxylic acid group, an alkali or alkaline earth metal salt thereof, an ammonium or organic amine salt thereof or a lower hydrocarbyl ester thereof, wherein "lower hydrocarbyl" includes straight, branched or cyclic saturated or unsaturated hydrocarbyl groups containing no more than 8 carbon atoms. Preferablyl n is o and Rl is methyl.
In Formula (II) above, the aliphatic groups preferably contain 1 to 8 carbon atoms, the alkenyl and alkynyl groups preferably contain 2 to 8 carbon atoms, the alicyclic groups prefer-ably contain 3 to 8 carbon atoms and the aromatic moiety is prefer-ably phenyl, although other ring systems, including heterocyclic ring systems, may be employed if desired.
In Formula (II) above, X is preferably CF3, Br or Cl and most preferably X is Br. The most preferred compounds are those in which X is Br and Z is ll - CH - C - O - R"
wherein R" is hydrogen, Cl-C8 alkyl, e.g., methyl, ethyl, propyl, isopropyl, isobutyl, n-butyl or n-octyl, or meth-oxypropyl.
Preferred active ingredients are fluorophenoxyphenoxy-propionates of the formula (I):

~ O ~ O ~ OCHCOOH (I) wherein ~25~
4693-347~D

X represents -Cl, -CF3, -I, -Br, -OCF3, F, -CF2Cl, -CF2H or -ocF2ccl2Hl and agriculturally acceptable derivatives (salts, amides and estersl thereof.
The compounds of the above Formula I, have been found to be active as herbicides in the presence of broadleaf crops and are unexpectedly superior in activity compared to compounds known in the art. Additionally, compounds of Formula (I), above,wherein X is -Cl and particularly wherein X is -Br, are surprisingly selective to small grain crops, such as wheat and barley, i.e., substantially non-phytotoxic to small grain crops. Accordingly, the invention of the parent application also encompasses herbicidal compositions containing one or more active ingredients as well as methods of controlling unwanted vegetation in such crops. Such methods comprise, for example, applying a herbicidally effective amount of one or more active ingredients preemergently or postemergently to the locus of the undesired vegetation, and part-icularly to the locus where a valuable crop is to germinate and grow.
The phenoxyphenoxy compounds of Formula (II), also referred to as "active ingredients", above are prepared employing procedures analogous to well known procedures for preparing known phenoxyphenoxyalkanecarboxylic acids and derivatives thereof as described in the known art. For example, some of the compounds of Formula (II) - 10a -~2sq~9~

above are prepared by reacting an appropriately substi-tuted 1,2-difluorobenzene wi-th an alkali or alkaline earth metal salt of an appropriate hydroxyphenoxy com-pound in a suitable solvent medium, such as dimethyl-sulfoxide~(DMSO), dimethylformamide ~DMF), N-methyl-pyrollidone, hexamethylpyrophosphoramide, tetrahydro-furan (THF), or acetonitrile. The reaction is advan-tageously carried out at~an elevated temperature of from 65C to 220C. This reaction can be characterized as follows:

F metallic F
X ~ F ~ HO ~ base wherein X and Z are as hereinbefore defined. This reaction is preferred when preparing compounds of Formula II wherein X is CF3.

Compounds of Formula (II) above wherein X
is -Cl or -Br are preferably prepared by reacting an alkali or alkaline earth metal salt of 4-(4'-chloro or bromo-2l-fluorophenoxy)phenol with an halo-Z compound, wherein Z is as defined in Formula (II), in a suitable solvent medium, such as, DMSO, DMF, THF, N-methyl-pyrrolidone, hexamethylpyrophosphoramide, or acetonitrile.
This reaction is advantageously carried out at an elevated temperature of from 40C to 220C. This reaction can be characterized as follows:

F metallic F
~ ,~ base ~ r-~
30 X {O ~ ~ OH ~ halo solvent 31,624-F -11-~2S729~;

wherein X' is Cl or Br, Z is as hereinbefore defined and the metallic base is a base, such as, for example Na2CO3 or K2CO3. However, organic bases such as triethylamine can also be used.

4-(4-(substituted)-2-fluorophenoxy)phenol and salts thereof are novel intermediate compounds and are within the scope of the present invention. These intermediates can be prepared by hydrogenating 4-(4'--(substituted)-2'-fluorophenoxy)nitrobenzene with hydrogen in the presence of a Raney nickel catalyst.
This reaction can be characterized as follows:

F Raney nickel F
r~~ catalyst r-~ r~~
~ ~ 2 ~ H2 > X ~ O ~ 2 wherein X is as defined hereinbefore. 4-(2'-Fluoro-4'-(substituted)phenoxy)benzeneamine, also a novel compound and contemplated by the present invention, is reacted with fluoroboric acid (HBF4), sodium nitrite and water to form the tetrafluoroborate of 4-(-4--(substituted)-2-fluorophenoxy)benzene diazonium.
This reaction can be characterized as follows:

F NaN02 F
~ ~ + ~BF ~2 ~ X ~ ~ N2 BF4 4~(2-fluoro-4-substituted phenoxy)benzenediazonium tetrafluoroborate, another novel compound is reacted with (a) aqueous sulfuric acid with heat or (b) an alkali metal trifluoroacetate in trifluoracetic and water in accordance with the procedures taught in D. E. Horning et al., Can. J. Chem., 51, 2347, (1973~, 31,624-F -12-~2~i7296 resulting in the formation of 4-(2-1uoro-4--(substituted)phenoxy)phenol. Thesa reactions can be characterized as follows:
F ~l~504/H20/~ F

X ~ ~ 2 4 ~ CF3C0 CF3 co2e~D
~2) ~2 Preferred compounds o:E the invention oE the parent application are the compounds of Formula (I) above wherein X
represents -CF3, -Br or -Cl, i.e., 4-(2-fluoro-4-(chloro, bromo or trifluoromethyl)phenoxy)phenoxy propionic acid and agricult-urally acceptable derivatives thereof. These preferred compounds are prepared by reacting the appropriate starting materials employing the procedures set forth above. The 4'-trifluoromethyl--2'-fluorophenoxyphenoxy propionates are prepared by reacting 1,2-difluoro-4-trifluoromethylbenzene with a salt of 4--hydroxyphenoxypropionic acid or a derivative thereof, i.e., an ester, or amide derivative of tne 4-hydroxyphenoxypropionic acid.
This reaction can be characterized as follows:
CH 3 metallic F3C- - ~ F +HO~OCHZ' solvent ~F CH3 F3C- ~O_~-CHZ ' ~L:257;29~ 9 wherein Z' represents -CO2H (the acids), -CO2M', ~C02R8, -COSR8, -CoNR92, -CSN~I2, -CN, -C~20R9 or -CH22cR ;
M' represents Li, Na, K, Mg, Ba or Ca, and corresponds to the cation of the metallic base, or N(R10)4;

R8 represents C1-C8 alkyl, C3-C6 cycloalkyl, alkenyl, alkynyl, or alkoxyalkyl;

each R9 independently represents H or Cl-C4 alkyl; and R10 independently represents H, C1-C4 alkyl or C2-C3 hydroxyalkyl.

The 4'-chloro-2'-fluorophenoxyphenoxy propionates are prepared by reacting a 4-(4-chloro-~2-fluorophenoxy)phenol with a halopropionate in the presence of a base and solvent as described above.
This reaction can be characterized as follows:

F CH3 metallic ~ r-~ ' base Cl ~ O ~ OH + Halo-CHZ' solvent Cl ~ O ~ CH3 wherein Z' is as defined above.

31,624-F -14-~:257:~

The 4'-bromo-2'-fluorophenoxy propionates are prepared by reacting a 4-(4-bromo-2-fluorophenoxy)-phenol with a halopropionate in the presence of a hase and solvent as d~scribed above. This reaction can be characterized as follows:

F CH3 metallic Br ~ O ~ OH + Halo-CHZ' solvent >

Br ~ O ~ OCHZ' wherein Z' is as defined above.

The terms "Cl-C4 alkyl" and "C1-C~ alkyl"
refer to difIerent size alkyl groups which may be straight, branched, or cyclic, when the group contains at least three carbon atoms, and, contain 1-4 or 1-8 ca~bon atoms respectively. The terms "C2-C3 hydroxyalkyl"
and "C3-C6 hydroxyalkyl" refer to different size hydroxy-alkyl groups having 2-3 or 3-6 carbon atoms, respectively, and the alkyl portion may be straight or branched, or cyclic when the group contains at leasc three carbon atoms.
Once prepared, the compounds are recovered employing standard, well-known, extraction and purifîcation techniques, such as, for example~ solvent extraction with ether.
The following examples further illustrate the present invention and that of the parent application. No attempt has been made to balance any equations described herein.

Example 1: Preparation of 2-[4-(2-fluoro-4-trifluoro-~ethylphenoxy)phenoxy]propionic acid methyl ester ~ ~ OC~COCH3 Step A

Cl F

2 + KF - ~ ~ N02 A stirred mixture of potassium fluoride ~58 grams (g), 1 mole) and potassium carbonate (2 g) in sulfolane (300 ml) was subjected to vacuum distillation until 75 ml of liquid had distilled. This effectively removes any moisture from the system. The distillation head was removed and 4-chloro-3-nitrobenzotrifluoride (95 g, 0.42 mole) was added. The resulting mixture was heated at 190C for two hours, then allowed to cool to approximately 100C. A 6 inch Vigreaux column was added to the reaction flas~, and the product rapidly distilled under vacuum (~1 mm). The light yellow liquid so obtained was mostly the desired 4-fluoro--3-nitrobenzotrifluoride but contained small amounts of sulfolane (~4 percent) and starting material. This liquid was dissolved in pentane (600 ml), washed with water (3 x 500 ml), then dried (MgSO4). Removal of the solvent and distillation of the yellow residual liquid gave 59 g (67 percent) of the desired product which had 31,624-F -16-~Z5~

a boiling point (b.p.) of 51C at ~1 mm. The nuclear magnetic resonance (NMR) (CDC13) spectra was consistent with the assigned structure.

Step B

F F

~$ N02 H2 ~NH2 10 A mixture of 4-fluoro-3-nitrobenzotrifluoride (59 g, 0.282 mole) and Raney Nickel (RaNi) (Aldrich, 5-spoonula scoops) in ethanol (350 ml) was hydrogenated on a Paar apparatus (starting pressure = 50 psi) until the theoretical amount of hydrogen had been consumed (~7 hours). The catalyst was filtered off (celite) and the ethanol was carefully evaporated on the rotary evaporator (some product is lost in this process). The residue was distilled to give 39 g (77 percent) of the desired aniline as a nearly colorless liquid which Z0 quickly turns yellow on standing. The product had a b.p.
of 41C at ~1 mm. The N~R (CDCl3) spectra was consistent with the assigned structure.

Step C

F F
25 ~ + HBF4 2 ~ ~ N2sF4 31,624-F -17-` ~ ~2572g6 A mechanically stirred solution o~ 3-amino-4~fluorobenzotrifluoride (17.9 g, 0.1 mole) in 48 percent fluoboric acid (72 g ~0.4 mole of HsF4) and water (100 ml) was cooled to ~5C in an ice-salt bath.
To this solution was slowly dropped a solution of sodium nitrite (7.25 g, 0.105 mole) in water (10 ml).
Soon after the addition began, a solid began to separate.
After about one-quarter of the sodium nitrite solution had been added, the reaction mi~ture had become very thick. It was necessary to stir very vigorously with an efficient stirrer in order to complete the reaction.
After the addition was complete, stirring at ~5C was continued for an hour, then the solid diazonium salt collected by filtration (medium porosity funnel). The salt was washed with cold 5 percent HBF4 solution (75 ml), then with several portions o~ cold ether.
This material was then dried overnight in a vacuum oven over P2O5 at 60C to give 22 g (79 percent) of the diazonium tetrafluoroborate ~shown above) as an off-white solid. The NMR (d6-acetone) spectra was consistent with the assigned structure.

Step D

F F
~ N2 BF4 ~00-220C > $ F

The diazonium salt (22 g) from Step E, which is shown above, was placed in a round-bottom flask (250 ml) e~uipped with a Dean-Stark trap and a condenser through which ice-water was circulated~ ~he top of the condenser was connected to a trap containing 31,624-F -18-`~ ~L257~g6 ~

10 percent NaOH solu-tion. The flask was immersed in an oil bath heated to 200-220C. The salt melted, turned dark and decomposed slowly, at first, then decomposed much more vigorously. The decomposition was accompanied by large amoun~s of gas and smoke. The desired 3,4-difluoro-benzotrifluoride which distilled was collected in the Dean-Stark trap as a dark red li~uid (6 g). This was taken up in pentane (20 ml) which was then stirred with MgSO4 and Na2CO3, filtered and distilled to give pure 3,4-difluorobenzotrifluoride (3.25 g, 22.5 percent) as a colorless li~uid having a b.p. of 104C.
Step E

F
15 ~ + HO ~ OCHCOCH3 ~ F3C ~ O ~ ' 3 A stirred mixture o~ 3,4-difluorobenzotrifluoride (1.82 g, 0.01 mole), methyl 2-(4-hydroxyphenoxy)propionate (2.72 g, 0.01 mole) and potassium carbonate (1.5 g) in DMSO (20 ml) was heated at 100-110C for 90 minutes.
After cooling, the mixture was poured into water (200 ml), then extracted with ether (2 x 100 ml). Pentane (50 ml) was added to the ether extracts, and this was washed with water (200 ml). After drying (MgSO4) the solvent was evaporated to give the desired phenoxyphenoxypropionate 30 (2.0 g, 55.9 percent) shown above as a pale yellow oil with a refractive index (R. I . ) of 1.4998 at 25C. The NMR (CDC13) spectra for H and 19F were consistent with the assigned structure.

31,624-F -19-~L25~72g~

Example 2: Preparation of 2-[4-(4-chloro-2-fluoro-phenoxy)phenox~]propionic acid methyl ester F CH
Cl ~ O _ ~ ~ OCHCOOCH3 steP 2A
OH OH C ~
~ F CH2C12 ~ F Cl ~ F
~ ~ C12 -10 Cl A stirred solution of 2-fluorophenol (20 g;
0.178 mole) in methylene chloride (200 ml) was cooled to -10C in an ice-salt bath. Precondensed chlorine (12.62 g; 0.178 molej was then slowly bu~bled into the solution at such a rate that the temperature did not rise above -10~C. After all of the chlorine had been added, and -the green color dissipated, the reaction was chec~ed by gas chromatography (g.c.). Even though no chlorine remained, g.c. showed that besides the two chlorinated products, a fair amount (~25%) of the starting phenol remained. At this point there was little or no dichlorinated material present. Additional chlorine was bubbled into the reaction mixture until g.c. showed that all of the starting material had been consumed. At this point, the reaction mixture contained 3% of a dichlorinated material as well as an 8:2 mixture of monochlorinated products. The mixture was poured into water (300 ml) containing excess sodium bisulfite.
The organic layer was separated, dried (MgSO4) and the solvent evaporated to give 25.5 g of a light yellow 31,62~-F -20-~2sq2s6 liquid. Fluorine NMR (CDC13) showed that an 8:2 mixture of monochlorinated products to be present. It was presumed that the major isomer was the desired 4-chloro--2-fluorophenol and that this wouid react faster in 5 nucleophillic substitution reactions than the more sterically hindered 2-chloro-6-fluorophenol. This mixture was used directly in the next reaction (Step 2B).

Step 2B
OH OH
10 C1~ + F~3 2 IISO

F
Cl~ O~N02 To a stirred mixture of potassium carbonate (25.04 g; 0.18 mole) in DMSO (200 ml) under an argon atmosphere was added an 8:2 mixture (25 g; 0.171 mole) 20 (from Step 2A) of 4-chloro-2-fluorophenol (~20 g;
0.136 mole) and 2-chloro-6-fluorophenol (~5 g;
0.034 mole). To this mixture was added 4-fluoronitro-benzene (18.05 g; 0.128 mole) and the resulting mixture stirred at 100C for 30 minutes. At the end of this 25 time, g.c~ showed that the mixture contained ~peak areas) ~10% of 2-chloro-6-fluorophenol, ~3% of a dichloro-fluorophenol, a trace of 4-chloro-2-fluorophenol, and a single product peak. This mixture was poured into aqueous base (~1% NaOH) and the resulting mixture 30 extracted with ether (2 x 300 ml). The ether extracts were combinedj washed with water (an emulsion formed 31,624-F -21-125729~

which required a little saturated aqueous NaCl to break), dried (MgSO4) and the solvent removed to give an orange--red oil (34 g). 19F NMR (CDC13) showed that essentially a single isomer to be present. The material was subjected to Kugelrohr distillation (oven temp. = 135-145) to give the desired product as a light yellow oil (32 g):
RI = 1.6038 @ 25C. Recrystallization from hexane (free~er) gave the product as a white solid: m.p. =
55-57C.

10 The carbon, hydrogen and nitrogen content was:
Carbon Hydrogen Nitroqen Calculated:53.85 2.64 5.23 Found: 53.70 2.54 5.16 Step 2C
F F
Cl ~ o ~ 2 EtOH ~ ~ NH2 Raney Nickel, i.e., RaNi (3 scoopulas) was washed with water (2 x 300 ml) and then ethanol (2 x 300 ml). To this was added a solution of the phenoxy-nitrobenzene (29 g; 0.108 g) in ethanol (250 ml). The resulting mixture was hydrogenated in a Paar apparatus (initial H2 pressure = 50 psi) until the theoretical amount of hydrogen had been taken up (3-4 hours). The mixture was filtered and the solvent evaporated from the filtrate to give 25 g of a light yellow oil which solidified upon standing. ~n analytical sample was prepared by recrystallization from hexane: m.p. =
s5.5-87C.

31,624-F -22-57~2~6 The carbon, hydrogen and nitrogen content was:
CarbonHydroqenNitrogen Calculated: 60.64 3.82 5.89 Found: 60.493.77 5.85 Step 2D
F

Cl~ ~ 2 + NaN02 H20 ~ NaBF4 F
Cl ~ 0 ~ - N 2B F4 Concentrated hydrochloric acid (35 ml) was added all at once to a mechanically stirred suspension of the aniline (16.64 g; 0.07 mole) in water (70 ml) and the resulting mixture cooled to <5C in an ice bath. To this stirred mixture was slowly added (dropwise) a solution of sodium nitrite (5.0 g; 0.072 mole) in water (10 ml). The temperature was maintained at <8C during the addition. By the time the addition was complete, the mixture was essentially homogeneous.
After stirring at <5C for an additional 30 minutes, the solution was treated with charcoal, then filtered through celite. The filtrate was again stirred mechanically at c5C (ice bath) and a solution of sodium fluoroborate (10.98 g; 0.1 mole) in water (35 ml) was added rapidly. A solid separated immediately.
After stirring for an additional 15 minutes, the solid was filtered, washed with a small amount of ice water, then with cold ether (3 x 150 ml). The solid was air 31,624-F -23-` -- ~25~

dried for an hour, then completely dried in a vacuum oven over P2O5 at 80C for 3 hours. There was thus obtained the desired diazonium tetrafluoroborate (19 g; 84.7%) as an off-white solid. The NMR
(d6 acetone or CF3CO2H) of this material was consistent with the assigned structure and showed a low field, two-proton doublet for the protons ortho to the diazonium salt. This material was used directly in subse~uent reactions. (Step 2E of Example 2 and Example 3).

Step 2E
F

Cl ~ O ~ N+B-F 2 4/ 2 LCl ~ O ~ CH3 Cl ~ - O ~ OCHCOCH3 To a stirred solution of concentrated sulfuric acid ~8 ml) in water (32 ml) which was heated to a gentle boil, was slowly added the above tetrafluoroborate diazonium salt (from Step 2D) (4 g; 0.0125 mole). After the addition was complete, stirring and heating was-contained for 45 minutes, then the reaction poured into ice-water (~ 300 ml). The mixture was then extracted with ether (3 x 100 ml), the combined extracts dried 31,624-F -24-~ 257~

(MgSO4) and the solvent~~evaporated to give 1.2 g of a red oil. Thin layer chromotography (TLC) (silica gel, 7:3 hexane-ethyl acetate) and g.c. showed that this was one main product (phenol) contaminated by a minor product.- This red oil was dissolved in DMSO (10 ml), and then methyl 2-bromopropionate (0.9 gr .0054 mole) and potassium carbonate (0.84 g; 0.006 mole) was added and the resulting mixture stirred under an inert atmosphere overnight. After the addition of water (200 ml), the mixture was extracted with ether (2 x 75 ml). The combined ether extracts were washed with water (75 ml), dried (MgSO4) and the solvent removed to give 1.3 g of a red oil. NMR (CDC13) of this material was consistent with the desired 2-[4-(4-chloro-2--fluorophenoxy)phenoxy]propionic acid methyl ester.
The oil was chromatographed (130 g silica gel, 7:3 hexane--acetone), but this failed to remove the color. The material was taken up in methanol, treated with charcoal, filtered and evaporated to give a yellow oil: R.I. =
1.5509.

~xample 3: Preparation of 4-(4-chloro-2-fluoro-phenoxy)phenol ~5 C ~ o_ ~ 2 4 CF3CO2K

- F O
30 CL ~ O ~OCS::F;~_ _2 `.

Cl ~ O ~ OH

31, 624-F 25-;257~

A solution of potassium trifluoroacetate (0.03 mole) in trifluoroacetic acid (TFA) (60 ml) was prepared by the careful addition of potassium carbonate (2.07 g; 0.015 mole) to the trifluoroacetic acid. To this solution was added, with stirring, the diazonium tetrafluorobate salt prepared in Example 2, Step 2~, (7.5 g; .023 mole) and the resulting mixture stirred and heated at reflux for ~8 hours. NMR (CF3C02H) of the reaction mixture indicated that some diazonium salt remained. An additional amount of potassium carbonate ~2.07 g; 0.015 mole) was added and heating continued for 24 hours. ~gain, NMR indicated that a small amount of star-ting material remained.
Additional K2C03 (2.07 g~ was added and heating con-tinued for 24 hours. NMR now showed that the mixturewas essentially devoid of starting material. About 30 ml of TFA was removed by distillation and the resulting mixture poured into water (200 ml). This a~ueous mixture was stirred at 40-45C for 3 hours to hydrolyze the trifluoroacetate. After cooling, the mixture was extracted with ether (3 x 100 ml), and the ether extracts were treated with charcoal and then filtered through a short pad of silica gel. The filtrate was evaporated to give a dark viscous residue.
This was purified via HPLC (8:2 hexane-ethyl acetate) the second peak being collected. Removal of the solvent gave a viscous red oil which was homogeneous by TLC and g.c. NMR (CDCl3~ was consistent with the assigned structure. This material solidified upon standing for several days. The methodology employed in this example is analogous to the methods described in D. E. Horning et al., Can. J. Chem., 51, 2347 (1973).

31,624-F -26-`- ~.;257:~6 Example 4: Preparation of the R enantiomer of 2-[4-(4-chloro-2-fluorophenoxy)-phenoxy]propionic acid methyl ester Cl ~ O ~ H~j ~/ C2 3 D~SO

F ~\/
cl~o~o~

A mixture of 4-(4-chloro-2-fluorophenoxy)-phenol ~2.23 g; 0.01 mole), the methanesulfonate of S-methyl lactate (18.22 g; 0.1 mole, minimum of 90%
optical purity), and potassium carbonate (1.4 g;
0.01 mole) in DMSO (75 ml) was stirred at room temperature for 18 hours. After this period, the mixture was poured into water (500 ml) then extracted into ether (3 x 100 ml). The ether extracts were dried (MgS04), and the solvent evaporated. The residue was purified by preparative HPLC using 8:2 hexane-ethylacetate as the eluent. The first peak to elute (after the solvent front) was collected and the solvent evaporated. This gave 2.3 g (71%) of a light yellow oil whose 1H and 19F
NMR (CDC13) were consistent with the assigned structur~.
This material possessed an optical rotation of ~24.68 as measured at 25C. The refractive index was 1.5466.
Attempts to measure the optical purity using the optically active ~R shift reagent tris-[3-(trifluoro-methylhydroxymethylene)-d-camphorateo] europium ~III) 31,624-F -27-~EL25'7:~9~

were not successful. Based upon the optical purity of the starting lactate the optical purity is estimated to be between 75 and 95%.

Example 5: Preparation of 2-[4-(4-bromo-2-fluorophenoxy)phenoxy propionic acid methyl ester Step I
OH OH
10~ ~ Br 2 2 ~ ~F

Br To a stirred solution of 2-fluorophenol (22.4 g, 0.2 mole) in methylene chloride ~250 ml) which was cooled to ~3C in an ice bath, was added, all at once, bromine (31.97 g, 0.2 mole). The resulting solution was stirred at ice bath temperature for two hours and then at room temperature for 1 hour.
The mixture was poured into water (600 ml) containing excess sodium bisulfite. The organic phase was separated and the aqueous phase was washed with additional methylene chloride (Z00 ml). The combined organic extracts were washed with saturated sodium bicarbonate, dried (MgSO4) and the solvent evaporated to give the desired 2-fluoro-4-bromophenol as a colorless oil (34.5 g, 90%). The NMR (CDC13) was consistent with the assigned structure. The gc of this material showed tha-t it contained only a trace of the 2,6-isomer.
This material was used directly in the following step without additional purification.

31,624-F -28-~2S7~2~;

Step II F

Br ~ OH ~ F ~ NO2 - ~ Br ~ ~ NO2 To a stirred mixture of 2-fluoro-4-bromo-phenol (34.0 g, 0.178 mole),` and 4-fluoronitrobenzene ~25.12 g, 0.178 mole) in DMSO (250 ml) was added powdered potassium carbonate (27.8 g, 0.2 mole). The resulting mixture was maintained under an a~mosphere of argon and warmed to 100C (oil bath temp) for one hour. After cooliny, the mixture was poured into an ice-cold, lN NaOH solution (1000 ml) and extracted with ether (3 x 250 ml). The ether extracts were combined, washed with water (300 ml), dried (MgS04) and the solvent evaporated to give a yellow oil.
This material was crystallized from hexane-ether to yield 44.5 g (80%) of the desired product as a light yellow crystalline solid: m.p. = 62-64C;
NMR (CDC13) was consistent with the assigned structure.
The carbon, hydrogen and nitrogen content was as follows:

Carbon HYdrogen Nitrogen Calculated:46.1B 2.26 4.49 25 Found: 46.11 2.22 4.50 Step III

Br ~ O- ~ NO 2 _ , Br ~ ~ NH2 EtOH

31,624-F -29-~ ~257~916 Raney nickel (3 spoonulas) was washed with water (3 x 250 ml) and then ethanol (3 x 200 ml). To the catalyst covered with a small amount of ethanol, was added a solution of the 4-(4'-bromo-2'-fluoro-phenoxy~nitro benzene from Step III (9.36 g, 0.03 mole) dissolved in warm ethanol (75 ml). The solution was degassed with argon, then hydrogenated on a Parr apparatus with an initial hydrogen pressure of 50 psi.
When the theoretical volume of hydrogen had ~een consumed (~90 minutes), the mixture was degassed,and the catalyst removed via filtration (celite).
The solvent was evaporated to give a white solid.
Upon recrystallization of this material from methyl-cyclohexane,.it took on an orange coloration and the recrystallized product was tinted orange. A small amount which was recrystallized from hexane did not undergo this apparent slight decomposition. Regardless of the color, the NMR (CDCl3) was consistent with the desired product: m.p. = 98-99.5C; Yield =
7.7 g (91%). The carbon, hydrogen and nitrogen content was as ~ollows:

Carbon Hydrogen Nitroqen Calculated: 51.08 3.22 4.97 Found: 51.10 3.09 4.80 This material was used in the next reaction step.

31,624-F -30--31-~57~96 STEP IV
F
B~ ~ ~ ~Cl > FaBF

- Br~O~N2BF~e4 Concentrated hydrochloric acid (50 ml), (was added all at o~ce to a stirred suspension of 4-t4--bromo-2-1uorophenoxy)aniline (30 g, 0.106 mole) in water (llO ml). The resulting mixture was cooled to ~3~C in an ice bath and then a solution of sodium nitrite (8.07 g, 0.117 mole) in water (15 ml) was slowly added. During the addition, the temperature was maintained at <8C. When all of the sodium nitrite had been added, the mixture had become a homogeneous solution. After the addition was complete, the mixture was stirred at 3C for 20 minutes, treated with charcoal, and filtere~ :
through celite. The cold filtrate was poured into a 1 liter erlynmeyer flask (wide-mouth), equipped with a mechanical stirrer, and cooled in an ice bath. To this solution, vigorously stirred, was added a solution of sodium fluoroborate (17.6 g, 0.16 mole) in w~ter (50 ml). A white precipitate separated immediately and the mixture was almost too thick to stir. Stirring was continued for 15 minutes, then the product filtered (medium porosity funnel ?, washed with several portions of ice water and then with cold ether (3 x 100 ml). After air dryin~ for 30 minutes, the product was dried in a vacuum oven over P~O5 at 80C for 3 hours. There was thus obtained 37.5 g ~a4%) of the desired dia20nium salt~

.
31,624-F -31-~25729~i i.e., 4-(4-bromo-2-fluorophenoxy)phenyl diazonium tetrafluoroborate as a white solid. The NMR (CF3CO2H) was consistent with the assigned structure. This material was used directly in the next reaction step.

STEP V

Br ~ O ~ CF3CO2 E ~ ~OoCF

F ~/
Br ~ O ~ OH

Potassium carbonate (34.78 g, 0.25 mole) was carefully and slowly added to trifluoroacetic acid (200 ml). After the reaction had ceased, the diazonium salt (37 g, 0.097 mole) from Step IV was added, and the stirred solution heated at reflux for 18 hours. At the end of this period, the NMR of the reaction mixture showed the absence of any starting diazonium salt.
About half of the trifluoroacetic acid was distilled, then the residue poured into water (600 ml). This mixture was stirred at 50-60C for 1 hour, cooled, and extracted with ether (3 x 200 ml ) . The ether extracts were combined, washed with water, and then with saturated sodium bicarbonate (3 x 300 ml). The sodium bicarbonate wash was conducted carefully because of the generation of oam. The ether phase was then treated with charcoal and filtered through a short pad of silica gel. The ether was removed 31,624-F -32-~L~2S72~316 to give a yellow-orange oil. The pure phenol was obtained by prep HPLC (7:3 hexane-ethylacetate) with the second peak being collected (l-recycle). Removal of the solvent gave the desired produc-t as an orange oil (l9 g, 69%) whose NMR was consistent with the assigned structure. RI = 1.6056 @ 25C. The carbon and hydrogen content was as follows:

Carbon Hydrogen Calculated:50.91 2.85 10 Found: 51.20 2.89 STEP VI
F C~
Br ~ O ~ O~ ~ BrC~C02CH3 -F CH
Br ~ 0 ~ OCHCO2C~3 A mixture of the 4-(4-bromo-2-fluoro-phenoxy)phenol (5.66 g, 0.02 mole) from Step V, me-thyl 2-bromoproprionate (3.34 g, 0.02 mole) and potassium carbonate (3.06 g, 0.22 mole) in DMS0 (30 ml) was stirred, under an atmosphere of nitrogen, at room temperature for 18 hours. The mixture was poured into water (300 ml), and the resulting mixture extracted with ether (2 x 100 ml). The ether extracts were combined, washed with water (100 ml), dried (MgS04), and the solvent evaporated to give the desired 2-[4-(4-bromo-2-fluorophenoxy)phenoxy]propionic acid; methyl es-ter as a yellow oil (6.0 g, 81%);
R.I. = 1.5628; NMR (CDC13) was consistent with the 31,624-F -33-~257~

assigned structure. The carbon and hydrogen con-tent was as follows:

Carbon Hydrogen Calculated: 52.05 3.82 Found: 52.12 3.64 Example 6 - Preparation of the R enantiomer of 2-[4-(4-bromo-2-fluorophenoxy)phenoxy]-propionic acid methyl ester F CH
~ ,-~ \3 CO2CH3 DMSO
Br ~ O ~ OH + H ~ K2CO3 OMes F C\2 3 Br ~ O- ~ -O ~,' A mixture of the 4(4-bromo-2-fluorophenoxy)-phenol (2.83 g, 0.01 mole), the methanesulfonate of S methyl lactate t18.2 g, 0.01 mole), and potassium carbonate (1.67 g, 0.012 mole) in DMSO (70 ml) was stirred at room temperature for 40 hours, then poured into water (700 ml). The mixture was extracted with ether (2 x 200 ml). Pentane (100 ml) was added to the combined ether extracts and the resulting solu-tion washed with water (300 ml). The organic phase was dried (MgS04) and the solvent evaporated to give a light yellow oil ~7 g). This oil was purified via prep HPLC (8:2 hexane - acetone) with the first peak being collected. Removal of the solvent gave the desired product enriched in the "R" enantiomer;

31,624-F -34-`~ ~

~257Z96 Optical rotation = + 20.34 @ 25C. R.I. = 1.5614 @25C; NMR (CDC13) was identical with that obtained in Example 4. No attempt was made to determine the optical purity of this material.

Example 7. Preparation of 2-(4-(4-Bromo-2-fluorophenoxy)-phenoxy)propionic acid.

F F

~0 ~r ~ ~ OCHCOCH3 ~ > ~ ~ ~ CHCO~

A solution of the methyl ester from Example S
(76 g, .206 mol) in ethanol (200 ml) was added to a stirred solution of potassium hydroxide (26.4 g, 85% KOH, 0.4 mol) in ethanol (250 ml). The resulting mixture was stirred for 30 minutes, then the solvent evaporated. The residue was dissolved in water (200 ml), the resulting solution acidified with concentrated hydrochloric acid, and then extracted with ether. The ether extracts were dried (MgSO4) and then the solvent evaporated to give the crude acid as an off-white solid. Recrystallization from methylcyclohexane gave 68 g (93%) of the desired acid as a light tan solid. hn analytical, sample was prepared by a second recrystallization from methylcycloh~xane:
m.p. = 120~121C. Calc. C: 50.72; H: 3.41.
Found: C: 50.84; H: 3.46.

31,624-F -35--36- ~2S7~6 Example 8. Preparation of 2-(4-(4-Bromo-2-fluorophenoxy)-phenoxy)propionyl chloride.

Br ~ ~ OCHCOH + SOC1 Br ~ O- ~ OCHCC1 O

A stirred mixture of the acid from Example 7 (61.8 g, 0.174 mol), benzene (500 ml), thionyl-chloride (21.77 g, .183 mol) and dimethylformamide(DMF, 2 ml) was heated at reflux for one hour. After cooling, all volatile material was evaporated to give a quantitative yield of the crude acid chloride as a bronze colored oil. This material was used in subsequent reactions without further purification.

Example 9. Preparation of Propionic acid: 2-(4-(4-bromo--2-fluorophenoxy)phenoxy), n-butYl ester.

~C~-oCHCCl ~ CH3CH2CH2CH20H G;>

/ CH
Br_ ~ ~ OCHC 2 2 2 3 31,624-F -36-To a stirred solution of n-butyl alcohol (0.75 g, 0.01 mol), pyridine (0.8 g, 0.01 mol), and 4-dlmethylaminopyridine (DMAP, catalytic amount) in dry ether (30 ml) was slowly dropped a solution of the acid chloride (3.73 g, 0.01 mole) in ether (10 ml).
After the addition was complete, the stirred mixture was heated at reflux for one hour, cooled, thPn poured into cold 2N HCl (100 ml). The ether phase was separated, washed with saturated sodium bicarbonate solution, treated with charcoal, then filtered through a pad of silica gel. The filtrate was dried (MgSO4) and the solvent evaporated to give the ester as a light yellow oil (3.7 g, 90%): Refractive Index (RI) = 1.5409 @
25C. Calc. C: 55.48; H: 4.90. Found C: 55.74;
H: 4.94.

In a similar manner the following esters were prepared:

31,624-F -37-~Z572~36 Br ~ O ~ -CH-C-R
Analysis R RI or MP Calc'd Found _oc~2cH2ocH2cH3 1.5411 C, 53.41 53.50 H, 4.724.74 -OCH2(CH2)6cH3 1.5275 C, 59.10 59.26 H, 6.045.93 -OCH CH N(CH ) 1.5461 C, 53.53 53.59 2 2 3 2 H, 4.975.01 N, 3.293.30 --a 1.5531 C, 56.75 56 .89 H, 4.764.91 -OCH CH=CH 1.5555C, 54.70 54.94 2 2 H, 4.084.12 20 -OCH2c-cH 1.5633 C, 50.40 53.58 H, 3.953.62 CH3 1.5780 C, 59.34 58.83 -o- ~ H, 4.073.83 -S- ~ 1.603l C, 56.38 57.20 H, 3.613.63 31,624-F -38-~257296 Example 10. Preparation of 2-(4-(4-(Bromo-2-fluoro-phenoxY)phenoxy)propionamide.

~_ ~ C~CCl + NH

/ CH
Br~0~30CHCNH2 To a cold (approx. 5C), stirred mixture of concentrated agueous ammonia (25 ml) and ethyl acetate (25 ml) was slowly dropped a solution of the acid chloride (3.73 g, 0.01 mole) in ethyl acetate (20 ml).
After the addition was complete, the mixture was stirred 2Q at room temperature for one hour. The organic phase was separated and the agueous phase was extracted with a second (50 ml) portion of ethyl acetate. The organic phases were combined, washed with water (75 ml), then with saturated sodium chloride solution (75 ml), and dried (MgSO4). Removal of the solvent gave a guanti-tive yield of the crude amide as a white solid. Re-crystallization from methylcyclohexane gave an analytical sample: m.p. - 110-112C. Calc: C, 50.87; H, 3.70.
Found: C, 51.00; H, 3.75.

31,624-F -39-~257~296 Example 11. Preparation of N-EthYl-N-butYl-2-(4-(4 -bromo-2-fluorophenoxv)phenoxy) proponamide.

/ CH3 Et Br ~ CHCCl +
O Bu Br ~ ~ ~, ~
O u To a stirred solution of N-ethyl-N-butylamine (2.12 g, .021 mol) and 4-dimethylaminopyridine (catalytic amount) in ether (30 ml) was slowly dropped a solution of the acid chloride (3.73 g, .01 mol) in ether (10 ml).
After the addition was complete, the mixture was stirred and heated at reflux for 30 minutes cooled, then poured into 2N
hydrochloric acid (100 ml). The ether phase was separated and the aqueous phase washed with additional ether (50 ml).
The organic phases were combined, washed with saturated sodium bicarbonate (100 ml), treated with charcoal, then filtered through a short pad of silica gel. The filtrate was dried (MgSO4) and the solvent evaporated to give 3.9 g (89%) of the desired amide as a light yellow oil: RI =
1.5512 @ 25C. Calc: C, 57.54; H, 5.75. Found: C, 57.55;
H, 5.77.

The following derivatives were prepared in a similar manner.

31,624-F -40--41- ~2572~

/ CH
Br ~ O ~ -CH-C-R

Analysis R RI or MP Calc'dFound .
~CH
10-~ 3 1.5944 C, 59.47 59.09 Ph H, 4.314.19 N, 3.152.93 -NCH CH=CH 1.5730 C, 54.83 54.66 2 2 H,4.354.21 N.3.553.44 -NHCH(CH3)2 101-104C C,54.5655.28 H,4.834.78 N,3.543.52 -NH ~ CF 137-139C C,53.0353.14 3 H,3.243.16 CH3 N,2.812.76 - ~ 1 69.5-71C C,55.1955.33 ~==J H,3.793.51 N,2.932.93 - ~ 54-55C C,57.4058.04 H,4.164.34 N,3.043.12 - ~ 1 127-129 C,54.2754.12 H,3.473.38 N,3.072.87 -NHOCH2 ~
N 1.5954 C,54.6854.39 H,3.933.95 N,6.076.08 ~N(CH3)2 ~N=C~
~N(CH3)2 1.5840 C,53.1052.02 H,5.125.11 ~,9.299.05 31,624-F -41-~2S7Z96 Example 12. Preparation of ProPionic Acid: 2-(4-(4--bromo-2-fluorophenoxy)Phenoxy), 4-nitrophenylhYdrazide.

Br ~ ~ CHCCl + H2 ~ 2 / CH
Br ~ ( ~ OCHCNHNH ~ N02 To a stirred solution of 4-nitrophenylhydrazine (3.06 g, .02 mol) and 4-dimethylaminopyridine (catalytic amount) in tetrahydrofuran (THF, 40 ml) was slowly dropped a solution of the acid chloride (3.73 g, 01 mol) in THF
(10 ml). After the addition was complete, the mixture was - 20 stirred for 30 min at room temperature, then poured into 0.5N hydrochloric acid (150 ml). The product was extracted into ether. The ether phase was treated with charcoal, filtered through a short pad of silica gel, dried (MgSO4), then the solvent evaporated to give the desired hydrazide (4.2 g, 89%) as an orange solid. Recrystallization from a small volume of toluene gave an analytical sample:
m.p. = 177-180C. Calc: C, 51.45; H, 3.50; N, 8.57.
Found: C, 51.63; H, 3.30; N, 8.69.

31,624-F -42-~.~i2572~6 -Example 13. Preparation of Methyl 2-(4-(2,4-difluoro-~henoxy)phenoxy)propionate.

~ CH3 HCl NaBF4 Q
2 ~ ~ CHCQCH3 + NaN02e=~> ~=~
O

~ C~I3 F ~ o~ 3 0CHCoCH3 To a cold (less than 5C) stirred solution of the aniline (6.11 g, .02 mole), concentrated hydrochloric acid (6 ml), and water (50 ml) was slowly dropped a solution of sodium nitrite (1.52 g, .022 mol) in water (10 ml). After the addition was complete, the mixture was stirred for 15 minutes then quickly filtered through celite to remove some insoluble material. The insoluble material was washed with several portions of ice water.
To the cold (less than 5C), vigorously stirred filtrate and washings, was added a solution of sodium tetra-25 fluoroborate (4.39 g, .04 mol) in water (50 ml). The yellow solid which separated was filtered, washed with ether, then dried overnight on a porous plate. The driedl solid diazonium tetrafluoroborate (7.5 g) was placed in a 250 ml round bottom flask and heated at 30 190-200C for approximately 5 min. As the salt melted it decomposed with gas evolution. After cooling, the dark residue was taken up in ether (150 ml), washed wi-th saturated sodium ~icarbonate, dried (MgSO4) and purified by preparative ~LC using 8:2 hexane/ethyl acetate as the 31,624-F -43-25729~

eluent. This first component to elute was collected, and the solvent evaporated to give the desired difluoro-phenoxyphenoxypropionate as a light yellow oil (1.6 g, 28%); RI = 1.5276 @ 25C. Calc: C, 62.33; H, 4.58.
Found: C, 62.31; H, 4.43~

Example 14. Preparation o~ 2-(4-(4-Bromo-2-fluoro-~henoxv~phenoxy)proPionaldehyde.

Br ~ ~ CHCOCH3 ~ Dibal-H

/ CH
Br~r~OCHCH

A stirred solution of the ester (3.7 g, .01 mol) in toluene (150 mol), under an atmosphere of nitrogen, was cooled to -78C using a dry ice/acetone cooling bath. To this was slowly dropped a solution of diisobutylaluminum hydride (Dibal-H, 11 ml of 1.2 M solution, .013 mols) in toluene. During the addition the temperature was maintained at less than -70C. After the addition was complete, the mixture was stirred an additional hour. While maintaining the temperature at less than -70C the reaction was quenched by the slow addition of a 75:25:6 ether/acetic acid/water solution (11 ml). The mixture was then warmed to room temperature, filtered ~ilter aid necessary), and the solvent evaporated. The oily residue was taken up in 31,624-F _44~

~25729~

ether and passed through a short column of silica gel.
Removal of the solvent gave the desired aldehyde (3.0 g) as a clear oil: RI = 1.5794 @ 25C. Calc: C, 53.11;
H, 3.57. Found: C, 52.99; H, 3.62.

The oxime, -CH=NOH, was prepared from the above aldehyde by standard procedures. It is a glass, having a R.I. = 1.5811. Calc: C, 50.87; H, 3.70;
N, 3.96. Found: C, 51.21; H, 3.73; N, 3.89.

Similarly, the ethylene glycol acetal, ,,,~
~0 was prepared from the above aldehyde by standard procedures. It is a light yellow oil having a 15 R.I. = 1.5678. Calc: C, 53.28; H, 4.21. Found:
C, 53.61; H, 4.08.

Example 15. Preparation of 2-(4-(4-Bromo-2-fluoro~henoxy)-phenoxv)Propanol.

/ CH
Br ~ -OCHCOCH3 + 2Dibal-H

F
¦ CH
Br ~ O ~ OCHCH2OH

31,624-F -45-`- ~257296 In a manner similar to the reduction described above, the es-ter was reduced to the corresponding alcohol using slightly more than two equivalents of Dibal-H. There was thus obtained the desired propanol as a light yellow oil: RI = 1.5780 @ 25C. Calc:
C, 52.80; H, 4.14. Found: C, 53.0; H, 4.04.

The benzoate ester, -CH 0-C ~
was prepared from the above alcohol by standard pro-cedures. It is a light yellow oil, RI = 1.5798.
Calc: C, 59.34; H, 4.07. Found: C, 59.35; H, 4.02.

Example 16. Preparation of N-Methanesulfonyl-2-(4-bromo-2-fluorophenoxy)phenoxy)propionamide.

B ~ ~ OCHCC1 ~ CH35O2 2 BX~- " ,, 3 To a stirred solution of metnanesulfonamide (1.5 g, 0.16 mol), and 4-dimethylaminopyridine (catalytic amount) in pyridine (20 ml) was slowly added, in a drop-wise manner, the neat acid chloride (3.7 g, 01 mol). The 31,624-F 46-57~296 reaction mixture was stirred for 5 days at room temperature, then poured into cold, 2N hydrochloric acid (250 ml). The resulting mixture was extracted with e-ther (2 x 100 ml~ and the aqueous phase discarded. The ether phase was then extracted with saturated sodium bicarbonate (2 x 50 ml) and the ether phase discarded. The aqueous phase was acidified to pH less t~lan 4 with concentrated hydrochloric I acid. The aqueous mixture was extracted with ether, the ether phases combined, dried (MgSO4) and the solvent evaporated to give the desired product as a white solid:
! m.p. 101-103C. Calc: C, 44.46; H, 3.50; N, 3.24.
Found: C, 44.45; H, 3.~0; N, 3.16.

Example 17. Preparation of Propanimidothioic Acid:
2-(4-(4-bromo-2-fluorophenoxy)phenoxy)-N-(1--methylethyl)-ethyl~-ethYl ester.

Br ~ ~ CHC-N~CH t CH3CH2SNa F

Br ~ ~ CHC=N~CH

To a solution of the imide chloride (2.7 g, .007 mols) (prepared by heating a solution of the compound where R is -NHCH(CH3)2 with a 10% excess of phosphorous pentachloride in chloroform for twenty four hours, then evaporating all volatile material) in dry te-trahydrofuran (50 ml) was added solid sodium eth~l mercaptide (1.85 g, .022 mol) in one portion. The resulting slurry was stirred overnight at room temperature, then poured into 31,624-F _a7_ -` ~L2S7~96 .
`` -48 ice water. The organic phase was separated, and the aqueous phase was washed with ether. The organic phases were combined, dried (MgSO4), and the solvent evaporated. The residue was purified via preparative HPLC (9:1 hexane/acetone as solvent). The first peak to elute was collected and the solvent evaporated to give 1.0 g (32%) of a yellow oil: RI = 1.5659 @ 25C.
The NMR (CDC13) of this material showed that it consisted of a 55:45 mixture of the syn and anti isomers of the desired thioiminoether. Calc: C, 54.55; H, 5.26 N, 3.18. Found: C, 54.84; H, 5.09; N, 3.03.

Example 18. PreParation of MorPholine: 4-(2-(4-(4--bromo-2-fluorobenoxyl)phenoxy)-1-((l-methylethYl)-imino)propY1.

F
Br_ ~ ~3 -OCHC=N~CH + HN
Cl CH3 Br ~ ~ ~C C=N~V~C~

In a manner similar to that described above, the imide chloride was condensed with an excess of morpholine in boiling ether. After filtration, and evaporation of the solvent, -the rPsidue was partitioned between ether and 2N hydrochloride acid. The ether phase was discarded, and the product isolated from the aqueous acid by adjusting the pH to 10, and ether 31,624-F -48~

~257~29~;

extraction. Drying (MgSO4) and removing the solvent, gave the desired morpholinoamidine as a viscous yellow oil (1.1 g, 35%): RI = 1.5610 @ 25C. The NMR (CDC13) of this material showed it to be a mixture of syn and anti isomers. Calc: C, 56.78; H, 5.63; N, 6.02.
Found: C, 56.95; H, 5.39; N, 5.89.

Exam~le 19. Preparation of 2~ 4-sromo-2-fluorophenoxy) ph noxv)propanoyl nitrile.

F F
B ~ CHCNH2 ~ poC13c-~Br ~ ~ c,H3 A solution of the amide (1.8 g, .0051 mol) and phosphorous oxychloride (POC13, 0.86 g, .0056 mol) in acetonitrile (20 ml) was stirred and heated at reflux for one hour, then additional POC13 (0.5 g) added. After heating for an additional hour, the cooled reaction mixture was poured into ice water (300 ml). The aqueous mixture was stirred for a few minutes, then extracted with ether.
The ether extracts were washed with saturated sodium bicarbonate, treated with charcoal, dried (MgSO4) and the solvent evaporated to give 1.4 g (82%) of the desired nitrile as a light yellow oil: R.I. = 1.5691 @ 25C.
Calc: C, 53.59; H, 3.30; N, 4.17. Found: C, 56.61;
H, 3.31; N, 4.21.
Alternatively, various other compounds may be prepared as illustrated by the ollowing examples and by employing appropriate starting materials.

~49--`' `~L2S7296 -50~

Example 20. Preparation of Methyl 2-(4~(2-Fluoro--4-nitrophenoxy)phenoxY)proprionate.

A stirred mixture of 3,4-difluoronitrobenzene (13.5 g, 0.85 mole), methyl 2-(4-hydroxyphenoxy)-propionate ~23.1 g, .085 mole), and potassium carbonate (12.5 g, .Og mole) in DMSO (200 ml) was heated in an oil bath (120 bath temperature) for one hour. After cooling the reaction mixtu e was poured into ice water (1000 ml) and the resulting mixture extracted with ether (3 x 200 ml). The ether extracts were combined, pentane (200 ml) added, and the resulting solution washed with 5% sodium hydroxide solution ~200 ~l), then with water. After drying (MgSO4), the solvent was evaporated to give 28 g (98%) of the desired product as a light-yellow oil which solidified upon standing.
Recrystallization from hexane-ether gave an analytical sample: m.p. = 67.5-69C; Calc: C, 57.31; H, 4.21;
N, 4.18. Found: C, 57.00; H, 4.13; N, 4.11.

Fxample 21. Preparation of Methyl 2-(4-(4-Amino-2-20 fluorophenoxY)phenoxy)propionate.
A solution of the nitro-compound (21.7 g, .065 mole) in ethyl acetate (200 ml) containing 5 palladium on charcoal (1.0 g) was subjected to hydrogenation on a Paar shaker (initial pressure =
50 psi) until the theoretical amount of hydrogen had been consumed. The catalyst was removed by filtration, and the solvent evaporated to give a guantitative yield of the desired aniline as a light yellow oil:
m.p. (HCl salt) = 145~150C; Calc (HCl salt): C, 56.23;
H, 5.02; N, 4.10. Found: C, 55.92; H, 4.89; N, 4.04.

31,624-F -50-~:2S'7296 Example 22. Preparation of MethYl 2-(4-(4-Bromo-2-~fluorophenoxy)phenoxy)propionate.

To a solu-tion of 48% hydrobromic acid (250 ml) and water (350 ml) was rapidly added the phenoxyaniline (92 g, .3 mole). The mixture was warmed until the solid, insoluble hydrobromide salt formed. The stirred mixture was cooled to less than 5C in an ice bath, then a solution of sodium nitrite (22.8 g, .33 mole) in water (40 ml) was slowly added. The addition was such that the reaction temperature was maintained at less than 6C.
After the addition was complete, the mixture was stirred for an additional 15 minutes, then the yellow diazonnium solution was added, in a rapid dropwise manner, to a warm, stirred solution of cuprous bromide (47.3 g, .33 mole) in 48% hydrobromic acid (100 ml). The CuBr/HBr solution was maintained at 65-75C by a warm water bath. After all of the diazonnium had been added, the dark mixture was stirred an additional 15 minutes, cooled to room temperature, and extracted with ether.
The ether extrac-ts were combined, washed with saturated sodium bicarbonate solution, dried (MgSO4) and the solven-t evaporated. The dark, viscous residue was subjected to bulb-to-bulb distillation to give the desired product (64 g, 58%).

Example 23. Preparation of Ethyl 4-(4-(4-Chloro-2--fluoroPhenoxy)phenoxy)pentanoate.

A stirred mixture of 4-(4-chloro-2-fluoro-phenoxy)phenol (2.3 g, .0103 mole), ethyl 4-bromo-pentanoate (2.01 g, .0103 mole), and potassium carbonate (1.46 g, .105 mole) in DMF (20 ml) was heated in an oil bath at 130C for one hour. Additional bromide (.05 g) and carbonate (0.5 g) were added each 31,624-~ ~51~

~2572~6 hour for the next four hours. At the end of this period, gas chromatography indicated that most of the s~arting phenol had reacted. After cooling, the reaction mixture was poured into 4N HCl solution (200 ml), and the product extracted into a 1:1 mixture of ether-pentane (2 x 150 ml). The organic extracts were combined, washed with 10% NaOH solution (200 ml), dried (MgS04), then the solvent evaporated. The resulting orange oil was purifisd via preparative HPLC (9:1 hexane/ethyl acetate) with the second peak beiny collected. Removal of the solvent gave ~he deisred ester as a light yellow oil: RI = 1.5344 @ 25C.
Calc: C, 62.21; H, 5.5~. Found: C, 62.38; H, 5.33.

Example 24. Preparation of Methyl 4-~4-(Bromo-2-f orophenoxy)phen XYILg~=3= ~O~

A stirred mixture of 4-(4-bromo-2-fluoxo-phenoxy)phenol (1.0 g, .0035 mole), E methyl 4-bromopent--2-enoate (0.71 g, .0037 mole) and potassium carbonate (0.56 g, .004 mole) in acetonitrile (15 ml) was heated at reflux for 90 minutes, then poured into ice water.
The resulting mixture was extracted with ether (2 x 100 ml). The ether extracts were combined, treated with charcoal, filtered through a short pad of silica gel, dried (MgS04), and the solvent evaporated to give the desired product as a yellow oil (1.2 g): RI =
1.5660 @ 25C. Calc: 54.70; H, 4.08. Found: C, 54.77;
H, 3.79.
The active ingredients, have been found to be suitable for use in methods for the preemergent and postemergent control of grasses, such as, barnyard grass, crabgrass, yellow foxtail and johnson grass, 3L2S72~6 in the presence of broadleaf crops, such as, cotton, soybeans and sugar beets~ Further, it has been surprisingly found that the compounds of Formula (I~ above where X is ~Cl or -Br are selective, i.e., exhibit little or no phytotoxic effects, to small grains, such as, wheat and barley.
For all such uses, unmodified active ingredients can be employed. However, the invention of the parent application embraces the use of a herbicidally-effective amount of the active ingredients in composition form with an inert material known in the art as an agricultural adjuvant or carrier in solid or liquid form. Such adjuvants or carriers must not be phytotoxic to valuabie crops particularly at the concentration employed in applying the composition in attempting selective weed control in the presence o~ crops. If weed control is desired in the absence of crops, it is generally sufficient to employ adjuvants of carriers which do not leave a persistent phytotoxic residue.
Thus, for example, an active ingredient can be dispersed on a finely-divided solid and employed therein as a dust. Also, the active ingredients, as liquid concentrates or solid composit-ions comprising one or more of the active ingredients can bedispersed in water, typically with aid of a wetting agent, and the resulting aqueous dispersion employed as a spray. In other procedures the active ingredients can be employed as a constituent of organic liquid compositions, oil-in-water and water-in-oil emulsions or dispersions, with or without the addition of wetting, dispersing, or emulsifying agents.

~L:257296 Suitable adjuvants of the foregoing type are well known to those skilled in the art. The methods of applying the solid or liquid herbicidal formulations similarly are well known to the skilled artisan.
Organic solvents that can be employed include toluene, xylene, kerosene, diesel fuel, fuel oil, and petroleum naphtha, ketones such as acetone, methylethyl ketone and cyclohexanone, chlorinated hydrocarbons such as trichloroethylene, and perchloroe-thylene, esters such as ethyl acetate, amyl acetate and butyl acetate, ethers, e.g., ethylene glycol monomethyl ether and diethylene glycol monomethyl ether, alcohols, e.g., methanol, ethanol, isopropanol, amyl alcohol, ethylene glycol, propylene glycol, butylcarbitol acetate and glycerine. Mixtures of water and organic solvents, either as emulsions or solutions, can be employed.
The active ingredients can also be applied as aerosols, e.g., by dispersing them by means of a compressed gas such as one of the fluorocarbons or one of its hydrocarbon successors.
The active ingredients can also be applied with solid adjuvants or carriers such as talc, pyrophyllite, synthetic fine silica, attapulgus clay, kieselguhr, chalk, diatomaceous earth, lime, calcium carbonate, bentonite, Fuller's earth; cotton seed hulls, wheat flour, soybean flour, pumice, tripoli, wood 10ur, walnut shell flour, redwood flour and lignin.
As stated, it is frequently desirable to incorporate a surface-acti~e agent in the compositions. Such surface-active or ~2572~6 wetting agents are advantageously employed in both the solid and liquid compositions. The surface-active agent can be anionic, cationic or nonionic in character.

~ypical classes of surface-ac-tive agents include alkyl sulfonate salts, alkylaryl sulfonate salts, alkylaryl polyether alcohols, fatty acid esters of polyhydric alcohols and the alkylene oxide addition products of such esters, and addition products of long-chain mercaptans and alkylene oxides. Typical examples of such surface-active agents include the sodium al~ylbenzene sulfonates having 10 to 1~ carbon atoms in the alkyl group, alkyl phenol ethylene oxide condensation products, e.g., p-isooctvlphenol condensed with 20 ethylene oxide units, soaps, e.g., sodium stearate and potassium oleate, sodium salt of propyl-naphthalene sulfonic acid, di(2-ethylhexyl)ester of sodium sulfosuccinic acid, sodium lauryl sulfate, sodium decyl sulfonate, sodium salt of the sulfonated monoglyceride of coconut fatty acids, sorbitan sesquio-leate, lauryl trimethyl ammonium chloride, octadecyltrimethyl ammonium chloride, polyethylene glycol lauryl ether, polyethylene glycol esters of fatty acids and rosin acids, e.g., Ethofat~ 7 and 13, sodium N-methyl-N-oleyl taurate, sodium dibutylnaphthalene sulfonate, sodium lignin sulfonate, polyethylene glycol stearate, sodium dodecyl benzene sulfonate, tertiary dodecyl polyethylene glycol thioether (nonionic 218), long-chain ethylene oxide-propylene oxide condensation products e.g., Pluronic~ 61 (molecular weight about 1000), polyethylene glycol ester of tall oil acids, sodium octophenoxyethoxyethyl sulfate, tris(polyoxyethylene)-sorbitan monostearate (Tween~ 60), and sodium dihexyl-sulfosuccinate.

31,624-F -55-~257296 The concentration of the active ingredients in solid or liquid compositions generally is from 0.003 to 95 percent by weight or more. Concentrations from 0.05 to 50 percent by weight are often employed. In compositions to be employed as concentrates, the active ingredient can be present in a concentration from 5 to 98 weight percent, pre~erably 15-50 weight percent. The active ingredient compositions can also contain other compatible additaments, for example, phytotoxicants, plant growth regulants, pesticides and the like and can be formulated with solid particu-late fertilizer carriers such as ammonium nitrate, urea and the like.
Other adjuvants, such as, for example, crop oil and crop oil concentrates, may also be included in the formulated compositions as is known to those skilled in the art.
The present compositions can be applied by the use of power dusters, boom and hand sprayers, spray dusters, by addition to irrigation water, and by other conventional means. The compositions can also be applied from airplanes as a dust or spray since the active ingredients are effective at very low application rates.
The active ingredients have been found to possess desirable herbicidal activity in general against grassy weeds such as foxtail, blackgrass, ~ohnsongrass, wild oats, barnyard grass and crabgrass in preemergent operations and also against the same grasses in postemergent operations. The active ingredients possess desirable herbicidal activity against the grassy weeds, described above, while at the same time are tolerant ~2~,7Z~ 4693-3474D

or selective to broadleaf crops, such as, cotton, soybeans and sugar beets. The compounds of Formula (I) where X is -Cl, and particularly where X is -Br, are surprisingly selective to small grain crops, such as, wheat and barley.
The exact rate to be applied is dependent not only on a specific active ingredient being applied, but also on a particular action desired (e.g., general or selective control), the plant species to be modified, and the stage of growth thereof as well as the part of the plant to be contacted with the toxic active ingredient. Thus, it is to be understood that all of the active ingredients and compositions contai.ning the same may not be equally effective at similar concentrations or against the same plant species. In non-selective preemergence and foliar treatments, the active ingredients are usually applied at an approximate rate of form 0.112 to 5.6 kgs/hectare, but higher rates may be appropriate in some cases such as 22.4 kgs/hectare or more. In preemergent operations for selecLive uses a dosage of 0.112 to 11.2 kgs/hectare or more is generally applicable, a rate of 0.112 to 4.48 kgs/hectare being preferred and 0.112 to 2.24 kgs/hectare being most preferred.
For controlling an infestation of annuals, a dosage of 0.112 to 0.56 kgs/hectare is generally utilized. When the infestation consists largely of perennials, a dosage of from 0.112 to 4.48, preferable 0.56 to 2.24 kgs/hectare should be employed.
In postemergent operations a dosage of 0.0112 to 22.4 kgs/hectare or more is generally applicable, although not all compounds are equally effective and some weeds are more difficult to control.

~Z5q2~
4693-347~D
A dosage rate in the range of 0.05~ to 0.84 kgs/hectare is preerred ~n selective postemergent control of annual grassy weeds, while about 0.112 to 5.6 kgs/hectare is preferred and more preferably 0.112 to 2.24 kgs/hectare for the selective postemergent control of perennial grassy weeds.
Example A - Postemergent Activity Representative compositions were evaluated for the postemergence control of species of plants listed in Table A. In these evaluations, plots of the plant species listed in Table A, grown to a height of about 10 cms, were used. Aqueous spary compositions, containing various amounts of 2-[4-(2-fluoro-4-trifluoromethylphenoxy~-phenoxy]propionic acid methyl ester, i.e., 125 ppm, 62.5 ppm, 31.25 ppm, 15.6 ppm, 7.8 ppm and 3.9 ppm, respectively, were applied to separate plots. The spray compositions were made by mixing the active ingredient in acetone to 1/2 the final volume, i.e., twice the final concentration. An equal amount of water was added to the active ingredient/acetone mixture wherein the water contained 0.1 percent by weight of TWEE~ 20 surfactant. The application to the plants was made to the point of run-off and was carried out with conventional spraying equipment. Other plots were sprayed with similar compositions Gontaining no toxicant to serve as controls.
Thereafter, the plots were maintained under conditions conducive for plant growth. Two weeks after treatment, the plots were examined for plant growth and evaluated on a scale of 0 to 100 where 0 represents no effect and 100 represents complete kill.
The results of the examination of the treated plots are set forth below in Table A.

3~257296 TABLE A
% Control at Indicated Dosa~e (ppm) Plant 12562.531.2515.6. 7.8 3.9 0.0 Wheat 100 100 100 90 60 0 0 Barnyard Grass 100 100 100 100 100 50 0 Crab-grass 100 100 100 100 100 90 0 Yellow 10 Foxtail 100 100 100 100 100 35 0 Johnson Grass 100 100 100 100 100 60 0 Wild Oats 100 100 100 60 0 0 0 At 125 ppm 2-[4-(2-fluoro-4-trifluoromethylphenoxy)-phenoxy]propionic acid methyl ester was inactive, i.e., no phytotoxic effect, against cotton, rape, soybeans, sugar beets, jimson weed, morning glory, pigweed, velvet leaf and cocklebur.

31,624-F -59-~s~æ~

Results of similar postemergent testing of 2-(4-(2-fluoro-4-iodophenoxy)phenoxy)propionic acid methyl ester were as follows:

Plant Species % Control of Indicated Dosage (ppm) 125 62.5 31.25 15.6 Wheat 0 0 0 0 Barnyard Grass 100 100 85 10 Crab-10 grass 100 100 100 100 Yellow Foxtail 100 100 100 90 Johnson Grass 100 100 100 90 15 Wild Oats 0 0 0 0 Example B - Postemergent Activity Substantially the same procedures as those described in Example A were repeated except that the active ingredients.were 2-[4-(4-chloro-2-fluorophenoxy)-phenoxy]propionic acid; methyl ester and its R-enantiomer and 2-(4-(4-bromo-2-fluorophenoxy)phenoxy propionic acid; methyl ester and its R-enantiomer. The results are listed below in Table B.

31,624-F -60-~ ~2S7296 TABLE B
4-Chloro-Species % Control_at Indicated Dosaqe (Ppm) 500250125 62.5 31.25 15.6 Wheat 40 0 0 0 0 0 Barley 50 0 0 0 0 Wild Oats 100 100 90 95 100 40 100 50 25 12.5 6.3 3.1 1.56 -Blackgrass 100 100 99 100 100 50 S0 Cheatgrass 40 10 0 0 0 0 0 Green Foxtail100 100100 100 100 100 9S
Yel-low Foxtail100 100100 100 100 80 50 4-Chloro- (R-Enantiomer) Species % Control at Indicated Dosage (pPm) 125 62.5 31.25 15~6 7.8 Wheat 60 70 0 0 0 Barley 40 0 0 0 0 Wild Oats 100 100 100 80 40 12.5 6.3 3.2 1.6 0.8 0.4 Blackgrass 100 100 95 90 80 40 0 Cheatgrass 0 0 0 Green Foxtail100 100 100 100 100 80 0 Yellow Foxtail100 100 60 40 0 0 0 31,624-F -61-57;296 4-Bromo-Species % Control at Indicated ~osaqe (ppm) 500 250 125 62.5 31.25 15.6 7.8 3.9 Wheat 0 0 0 0 0 0 5 Barley 30 10 10 10 0 0 0 0 Wild Oats 100 100 95 100 100 100 80 70 2512.56.25 3.1 1.5 0.8 0.4 0.2 Blackgrass100 100 99 70 50 30 10 0 Cheatgrass 0 0 0 0 0 0 0 0 10 Green Foxtail 100 100 100 100 100 90 90 20 Yellow Foxtail100 100 100 80 50 20 0 0 4-Bromo- (R-Enantiomer) Species % Control at Indicated Dosaqe (PPm) 250 125 62.5 31.25 15.6 7.8 3.9 1.9 15 Wheat 100 70 0 0 0 0 0 0 Barley 100 90 95 0 0 0 0 0 Wild Oats 100 10Q 100 90 90 80 80 60 12.5 6.3 3.1 1.5 0.8 0 4 0.2 0.1 Blackgrass100 100 90 90 60 50 0 0 20 Cheatgrass 0 o 0 0 0 0 0 0 Green Foxtail 100 100 100 100 100 100 50 0 Yellow Foxtail 100 100 100 60 20 0 0 0 Example C - Preemerqent ActivitY
In a representative operation, 2-[4-(2-fluoro--4-trifluoromethylphenoxy)phenoxy]propionic acid methyl ester, to be utilized in a series of tests, is dissolved in acetone ~o one half of the final volume 31,624-F -62-~25q296 ttwice the ~inal concentration) to be used and the acetone solution in each case is admixed with an equal volume of water containing 0.1 percent by weight of Tween-20 surface active material (Tween-20 is a trademark of Atlas Chemical Company). The composition, generally in the nature of an emulsion, was employed to treat separate respective seed beds of sandy loam soil o~
good nutrient content wherein each seed bed contained separate groups of good viable seeds, each group being of one of a known plant species. The various beds were positioned side by side and exposed to substantially identical conditions of temperature and light. Each bed was maintained so as to prevent any interaction with the test compound in different seed beds. Each seed bed was treated with the composition as a spray employing conventional spraying equipment to deposit a predetermined amount o~ the compound uniformly throughout the surface of the bed. Another seed bed was treated only with the acetone-Tween-20 water mixture with no chemical added to serve as a control. After - treatment, the seed beds were maintained for two weeks under greenhouse conditions conducive for good plant gr~wth and watered as necessary. The specific plant species, dosage and the percent preemergent control obtained are set forth in Table C below. Control refers to the reduction in growth of the test species in the presence of the test chemical relative to the observed growth of the same species in the absence of the test chemical.

31,624-F -63-~- ~ 25~

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tD ~-3 l , 6 2 4-F -6 4 -i~ :L2572~316 Example D - Preemergent Activity of Racemic (R,S) 2-[4-(4-chloro-2-fluorophenoxy)phenoxy]-propionie Aeid Methyl Ester and its R-enantiomer Substantially the same procedures described in Example C were repeated using as the active ingredients (1) racemic (R,S) 2-[4-(4-chloro-2-fluoro-phenoxy)phenoxy]propionie aeid methyl ester and (2) (R) 2-[4-(4-ehloro-2-fluorophenoxy)phenoxy]-propionie aeid methyl ester.

The results of the preemergence tests are listed in Table D below.

31,624 F -65-, ~25729~i;
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31 , 6 2 4-F - 6 6 -~257~

Example E
Employing the procedures set out above in Example C, the following data on preemergent activity of various compounds was obtained.

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31, 624-~ _70_ ~25729~

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31,624-F 73-i7~

Example F
To further define the selective postemergence herbicidal characteristics of the active ingredients, chemicals were applied to additional species of grasses as listed in Table F.
Chemicals evaluated were 2-[4(4-bromo-2-fluorophenoxy)phenoxyJ-propionic acid methyl ester and its R isomer. Treatment conditions were similar to those described in Example A except that chemicals were delivered through a track sprayer set to deliver the appropriate dosages in 280.6 L/hectare of water containing 0.1 %
Tween-20 surfactant. Results are presented in Table F.

~25~9~;

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o O ~D O O O ~D O O O .
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O 0~ ~D O O . ~ n o o o ~ o o o I I I I o ~_ 3 ' I' !' O ~ r~
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Z Z z Z Z Z Z Z z o n ~3 o ~3 ~3 o ~ 3 t-o _ 1. 1~ ~ .
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w ~ o w ~ w n ~ w ~n P~ ~ n 1l ~D o ~
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o o o o o o o o o o o I~ ~ I_ r ~s ~ w - 1' 1' )' 1' 0 n ~ ~
O ~D O O ~ O O O . ID
o o o o o o o o o o o o ~ ~
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o o o o o o o o o o o o ~ It rt w r~
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ooooooooooo o 31, 624~F -78-~L2~ii72~6 The active ingredients conta~n an optically active center as shown in Formula (I~ (2 position of the propanoic acid) and can exist in optically active steroisomeric forms such as the dextroro-tatory and levorotatory forms of each of the above configurations.
In further embodiments, the compounds or compositions containing the same, can be advantageously employed in combination with one or more additional pesticidal compounds. Such additional pesticidal compounds may be insecticides, nematocides, arthropodicides, herbicides, fungicides or bactericides that are compatible with the compounds in the medium selected for application and not antagonistic to the activity of the present compounds. Accordingly, in such embodiments, the pesticidal compound is employed as a supplemental toxicant for the same or for a different pesticidal use, or as an additament. The compounds in combination can generally be present in the ratio of from 1 to 100 parts of the compound with from 100 to 1 parts of the addit-ional compound(s).

Claims (11)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A compound of the formula wherein X represents -Cl, -Br, -CF3, -I, -OCF3, F, -CF2Cl, -CF2H
or -OCF2CCl2H or a salt thereof.

2. A compound of the formula wherein X represents -Cl, -Br, -CF3, -I, -OCF3, F, -CF2Cl, -CF2H
or -OCF2CCl2H or a salt thereof.

3. A compound as claimed in claim 2 wherein X is Cl.

4. A compound as claimed in claim 2 wherein X is Br.

5. A compound as claimed in claim 2 wherein X is I.

6. A compound of the formula wherein X represents -Cl, -Br, -CF3, -I, -OCF3, F, -CF2Cl, -CF2H
or -OCF2CCl2H.

7. A compound as claimed in claim 6 wherein X is Cl.

8. A compound as claimed in claim 6 wherein X is Br.

9. A compound as claimed in claim 6 wherein X is I.

10. A process for preparing a compound of formula or a salt thereof, in which X is as defined in claim 1, which pro-cess comprises hydrogenating a compound of the formula wherein X is as defined above, with hydrogen in the presence of a Raney nickel catalyst, and, where required, forming a salt thereof.

11. A process according to claim 10 further comprising the step of reacting the compound of formula so obtained with HBF4, sodium nitrite and water and further reacting the tetrafluoroborate so obtained a) with aqueous sulfuric acid and heat; or b) with an alkali metal trifluoroacetate in trifluoro-acetic acid and water, to obtain a compound of formula and, where required, forming a salt thereof.