Background and Summary of the Invention

This invention relates to substituted N-arylindoles , a process for producing them and their use as herbicides . In particular, this invention relates to substituted N-arylin¬ doles of the formula

in which:

R is hydrogen; halogen; nitro; cyano; alkyl; alkoxy; alkenyl- oxy; alkynyloxy; alkoxyalkyl; carbonylalkoxy; aIky1oxyalkoxy; cyanoalkoxy; benzyloxy; alkoxycarbonylalkoxy; alkylcarbonyl¬ alkoxy; haloalkyl; hydroxalkyl; formyl; azido; carboxy and its salts; COOalkyl; amino; substituted amino wherein the substi¬ tuents are alkyl, alkoxy, hydroxy, formyl, alkylcarbonyl, substituted alkylcarbonyl substituted with carboxy or alkoxy- carboxy, alkylsulfonyl, haloalkylsulfonyl, aminocarbonyl, (di)alkylaminocarbonyl, alkoxycarbonyl, alkoxyalkyl, hydroxy- ^" carbonylalkyl, alkoxycarbonylalkyl, amino and (di)alkyl amino; carboxyamido; substituted carboxyamide wherein said substi¬ tuents can be selected from alkyl, alkylsulfonyl, and halo¬ alkylsulfonyl; εulfonamido wherein the N is substituted with hydrogen and/or alkyl; YR 4 wherein Y is O and S(O) and R4 is selected from the group hydrogen, alkyl, haloalkyl, cyano-

alkyl, alkoxycarbonylalkyl, hydroxycarbonylalkyl and aminocar¬ bonylalkyl wherein the N is substituted with hydrogen and/or alkyl;

n is 0 to 4 and

n is 0 to 2;

R is hydrogen, alkyl, halogen, cyano, haloalkyl, alkoxy, and carboxy and its salts or esters;

q is 0 to 2;

X is hydrogen, halogen, cyano, nitro, alkylthio, alkylsul¬ finyl, alkylsulfonyl, and alkoxy;

k is 0 to 2;

Z is N and C-R 2; wherein R2 is hydrogen, halogen, haloalkyl, cyano, nitro, alkythio, alkylsulfinyl, alkylsulfonyl and alkoxy;

₃ R is hydrogen, haloalkyl, haloalkoxy, cyano, halogen, and

SO R 5 wherein R5 is alkyl or haloalkyl and y is 0, 1 or 2; and

agriculturally acceptable salts thereof.

Description of the Invention

Within the scope of the above formula, certain embodiments are preferred, as follows:

R is preferably halogen, nitro, alkoxy, cyano, lower alkyl, lower haloalkyl, amino, substituted amino, sulfonamido, alkylεulfonamido, alkythio, alkylsulfonyl, carboxyalkoxy and alkoxycarbonylalkoxy. Particularly preferred groups are fluoro, chloro, methoxy, alkoxyacetoxy, alkoxy-2-propionoxy, amino, sulfonamido, cyano and nitro, n is referabl 1 or 2.

is preferably hydrogen, methyl, halogen, and cyano. More preferably R is hydrogen and halogen.

X is preferably hydrogen, chlorine and fluorine.

Z is preferably N, C-H or C-halogen.

R 3 is preferably trifluoromethyl.

The term "alkyl ¹¹ and all groups containing alkyl portions are intended to include straight-chain, branched- chain and cyclic groups. Examples are methyl, ethyl, n- propyl, isopropyl, cyclopropyl, n-butyl and t-butyl. Each alkyl member may contain one to six carbon atoms. For example, (C ₁ -C ₈ )alkoxy(C -C ₈ )alkoxy; amino(C.-Cg)alkylcar¬ bonyl. The term "alkoxycarbonylalkoxy" includes alkyl groups that are straight-chain, branched-chain and cyclic with one to six carbon atoms. Examples are ethoxyacetoxy, ethoxy-2-pro- pionoxy and methoxy-2-propionoxy.

In the above definitions, the term "halogen" includes fluoro, chloro, bromo and iodo groups. The term "haloalkyl" refers to the alkyl group substituted by one or more halogen atoms.

The compounds of the present invention have been found to be active herbicides, possessing utility as pre- emergence and post-emergence herbicides and useful against a wide range of plant species including broadleaf and grassy species. As mentioned hereinbelow, some of the compounds demonstrate selective control of plant species in certain crops, such as rice, corn and soybean.

This invention therefore also relates to a method for controlling undesirable vegetation comprising applying to a locus where control of such vegetation is desired, either prior or subsequent to the emergence of such vegetation, an herbicidally effective amount of a compound as described

herein, together with an inert diluent or carrier suitable for use with herbicides.

The terms "herbicide" and "herbicidal" are used here¬ in to denote the inhibitive control or modification of unde- εired plant growth. Inhibitive control and modification include all deviations from natural development such as, for example, total killing, growth retardation, defoliation, desiccation, regulation, stunting, tillering, stimulation, leaf burn and dwarfing. The term "herbicidally effective amount" is used to denote any amount which achieves such control or modification when applied to the undesired plants themselves or to the area in which these plants are growing. The term "plants" is intended to include germinated seeds, emerging seedlings and established vegetation, including both roots and above-ground portions. The term "agriculturally acceptable salts" includes sodium, potassium, calcium, ammonium and magnesium salts.

The compounds of this invention are prepared by the following procedures:

GENERAL METHOD OF PREPARATION

The unarylated indoles as starting materials of the present invention are generally not novel and can generally be prepared by methods familiar to one skilled in the art or, in the alternative, they may be purchased. Indoles can be arylated on the nitrogen in the presence of bases, such as sodium hydride, potassium hydroxide and sodium hydroxide with an appropriate haloaryl or halo-heteroaryl group. One group of novel arylated indoles can be made by an analogus process - as that described in Organic Synthesis Collective, Vol. VII, pg. 34, A. D. Batcho and W. Leimgruber, using appropriate 2-methylnitrobenzeneε as starting materials.

The following examples teach the synthesis of a representative compound of this invention.

EXAMPLE 1

1-f3 '-chloro-5 '-trifluoromethyl-pyridyl-2 ' )-4-chloroindole

(Compound 34 in Table I)

A mixture of 20.0 ml dimethylsulfoxide and 0.25 grams [g] (8.3 millimoles [mmol]) 80% εodium hydride suspension in oil was stirred at room temperature. To the mixture waε added 1.0 g (6.6 mmol) 4-chloroindole and stirring continued at room temperature for 30 minutes. Slowly 1.4 g (6.6 mmol) 2,3-dichloro-5-trifluoromethyl pyridine was added, generating a slightly exothermic reaction. The mixture was stirred for 2 hours at room temperature.

Methanol (2.0 ml) waε added and εtirred for 5 minuteε. Thereafter, water and methylene chloride were added. The organic phase was separated, washed with water, dried over anhydrouε magneεium εulfate and εtripped under vacuum to yield 1.4 g of an-amber εe i-εolid. The proposed structure waε determined by infrared εpectroscopy, mass spectrometry and nuclear magnetic resonance spectroεcopy.

EXAMPLE 2

1-r2 ' .6 '-dichloro-4'-trifluoromethylphenyl1-4-nitroindole .Compound 14 in Table 1)

A mixture of 4-nitroindole (0.5 g, 3.0 mmol), potas¬ sium hydroxide pellets (0.7 g, 12.0 mmol) in 40.0 ml dimethyl- εulfoxide were εtirred for 30 minutes at room temperature. Then 3,5-dichloro-4-fluorobenzotrifluoride waε added and stirred at room temperature for 3 hours. Water and methylene chloride were added and the mixture was εtirred for 10 minuteε. The organic phaεe waε εeparated, waεhed with water, driedvand εtripped under vacuum to yield 1.0 g of yellow εolid of the deεired product. The structure waε confirmed by infra¬ red εpectroscopy, mass spectrometry and nuclear magnetic reεo- nance εpectroεcopy.

EXAMPLE 3

1-[2'-chloro-6'-fluoro- '-trifluoromethylphenyl] -4-methoxyindole

(Compound 18 in Table 1.

4-Methoxyindole (0.5 g, 3.4 mmol) and εodiu hydride (80% diεperεion in oil, 0.1 g, 3.9 mmol) were εtirred together in dimethyl εulfoxide (10 ml) at room temperature for 30 minutes, and then 3-chloro-4,5-difluorobenzotrifluoride (0.73 g, 3.4 mmol) was added slowly. The mixture waε εtirred at

room temperature for 2 hours, and then methanol (2 ml) waε added. The mixture waε partitioned between dichloromethane and water. The organic solution waε dried over magnesium εulfate, filtered and the filtrate evaporated in vacuo, and the reεidue further purified by flaεh column chromatography on εilica gel to give the title compound as a waxy εolid (0.4 g) . The structure waε confirmed by infra-red εpectroscopy, aεε εpectrometry and nuclear magnetic reεonance εpectroεcopy.

EXAMPLE 4

1-[3'-chloro-5'-trifluoromethylpyridin-2-y1] -6-methoxyindole

(Compound 32 in Table 1)

6-Methoxyindole waε prepared according to the proce¬ dure of P. L. Feldman and H. Rapoport (Synthesiε 735, 1986).

6-Methoxyindole (2.6 g, 18 mmol) and potasεium hydroxide (4.0 g, 72 mmol) were stirred together in dimethyl εulfoxide (60 ml) at room temperature for 30 minuteε, and then 2,3-dichloro-5-trifluoromethylpridine (4.0 g, 18 mmol) waε added εlowly. The mixture waε εtirred at room temperature for 4 hourε, and then partitioned between diethyl ether and water. The ethereal εolution waε dried over magneεium εulfate, filtered and the filtrate evaporated in vacuo to give a dark εolid reεidue (4.0 g) . Further purification by flaεh column chromatography on εilica gel gave the title compound (3.0 g) aε a pale yellow εolid, m.p. 68-70°C.

EXAMPLE 5

1-[3'-chloro-5'-trifluoromethylpyridin-2-yl] -6-hvdroxyindo1e

(Compound 64 in Table 1)

1-[3'-chloro-5'trifluoromethylpyridin-2-y1]-6- methoxyindole (1.9 g, 5.8 mmol) was disεolved in dichloro- methane (50 ml) and the mixture cooled to -70°C under an atmoεphere of nitrogen. A solution of boron tribromide (1.0 ml, 11 mmol) in dichloromethane (10 ml) waε added dropwiεe, and after stirring for 45 minutes at -70°C a further quantity (0.5 ml, 5.5 mmol) of boron tribromide waε added. The mixture waε εtirred for 15 minuteε, and then the temperature waε adjusted to 0°C and methanol (10 ml) added. The mixture waε εtirred for 30-minutes, and allowed to warm to room tempera¬ ture. The solvent waε removed in vacuo, and the reεidue partitioned between diethyl ether and water. The ethereal εolution waε dried over magneεium εulfate, filtered and the filtrate evaporated under reduced preεεure to give the title compound (1.3 g) as a waxy εolid. The εtructure was confirmed by infra-red spectroεcopy, maεs spectrometry and nuclear magnetic reεonance εpectroεcopy.

EXAMPLE 6

Methyl 2-[1-(3'-chloro-5 '-trifluoromethylpyridin-2-yl)- indol-6-yloxylpropionate

(Compound 46 in Table 1.

1-(3'-chloro-5-trifluoromethylpyridin-2-yl)-6-hydr— oxyindole (2.35 g, 7 mmol) and potaεεiu carbonate (2.4 g, 17.5 mmol) were εtirred together in N,N-dimethylformamide (40 ml) for 15 minuteε, and then methyl 2-bromopropionate (1.2 g, 7 mmol) waε added. The mixture waε εtirred at room tempera¬ ture for 18 hourε, and then partitioned between diethyl ether and water. The ethereal εolution waε dried over magnesium sulfate, filtered and the filtrate evaporated under reduced

preεεure to give the title compound ( 1.4 g) aε a waxy solid, The structure waε confirmed by infra-red spectroεcopy , aεε spectrometry and nuclear magnetic resonance spectroscopy .

EXAMPLE 7

2-[1-(3 '-chloro-5 '-trifluoromethylpyridin-2-yl)- indol-6-yloxγlpropionic acid

(Compound 47 in Table 1.

Sodium hydroxide (4% aqueous solution, 25 ml) waε added to a εolution of methyl 2-[1-(3'-chloro-5'-trifluoro¬ methylpyridin-2-yl)indol-6-yloxy]propionate (0.6 g, 1.5 mmol) in isopropanol (25 ml) and the mixture stirred until thin layer chromatography εhowed no remaining εtarting material. The iεopropanol waε removed by evaporation in vacuo, and the remaining aqueous εolution acidified with 2N agueouε hydrochloric acid and extracted with diethyl ether. The ethereal εolution waε dried over magneεium εulfate, filtered and the filtrate evaporated under reduced preεεure to give the title compound (0.5 g) aε a pale yellow εolid, m.p. 155-158°C. The εtructure waε confirmed by infra-red εpectroεcopy, maεε εpectrometry and nuclear magnetic reεonance εpectroεcopy.

EXAMPLE 8

1-r2 ' .6'-dichloro- ^/ -trifluoromethylphenyl)-6-methoxyindole

(Compound 15 in Table 1)

6-Methoxyindole (1.0 g, 6.8 mmol) and potaεεium hydroxide (1.5 g, 27 mmol) were εtirred together in dimethyl εulfoxide (40 ml) at room temperature for 30 minutes, and then 3,5-dichloro-4-fluorobenzotrifluoride (1.6 g, 6.8 mmol) waε added εlowly. The mixture waε εtirred at room temperature for 17 hourε, and then partitioned between diethyl ether and water. The ethereal εolution waε dried over magneεium εulfate, filtered and the filtrate evaporated in vacuo to give

the title compound aε a waxy εolid (2.3 g) . The structure waε confirmed by infra-red εpectroεcopy, maεε spectrometry and nuclear magnetic reεonance εpectroscopy.

EXAMPLE 9

ethyl 2-[1-(2',6'-dichloro-4'-trifluoromethylphenyl)indol- 6-yloxy1propionate

(Compound 48 in Table 1.

1-(2',6 '-dichloro-4'-trifluoromethylphenyl)-6-hydr- oxyindole (0.9 g, 2.6 mmol) and potassium carbonate (1.4 g, 10 mmol) were εtirred together in N,N-dimethylformamide (50 ml) for 5 minuteε, and then ethyl 2-bromopropionate (0.5 g, 2.6 mmol) was added. The mixture waε εtirred at room temperature for 18 hours, and then partitioned between diethyl ether and water. The ethereal εolution waε dried over magneεium εul¬ fate, filtered and the filtrate evaporated under reduced preε¬ εure to give the title compound (1.2 g) aε an amber colored oil. The εtructure waε confirmed by infra-red εpectroεcopy, maεε εpectrometry and nuclear magnetic reεonance εpectroεcopy.

EXAMPLE 10

2-[1-(2' ,6'-dichloro- '-trifluoromethylphenyl)indol- 6-yloxylpropionic acid

(Compound 49 in Table 1)

Sodium hydroxide (4% aqueouε εolution, 25 ml) waε added to a εolution of ethyl 2-[1-(2' ,6'-dichloro-4'-trifluoro¬ methylphenyl)indol-6-yloxy]propionate (0.5 g, 1.5 mmol) in iεopropanol (25 ml) and the mixture εtirred for 10 minuteε at room temperature. The iεopropanol waε removed by evaporation in vacuo, and the remaining aqueous solution acidified with 2N aqueous hydrochloric acid and extracted with diethyl ether. The ethereal solution waε dried over magnesium sulfate, fil¬ tered and the filtrate evaporated under reduced pressure to

give the title compound (0.4 g) aε a pale yellow solid, m.p. 170-17 °C. The εtructure waε confirmed by infra-red spectroε- copy, maεε εpectometry and nuclear magnetic reεonance εpec- troεcopy.

EXAMPLE 11

1-(2',6'-dichloro-4'-trifluoromethylphenyl)-6- proparσyloxyindole

(Compound 56 in Table 1)

1-(2',6'-dichloro-4'-trifluoromethylphenyl)-6-hydr- oxyindole (1.3 g, 4 mmol) and potaεεium carbonate (1.4 g, 10 mmol) were εtirred together in N,N'-dimethylformamide (50 ml) for 15 minuteε, and then propargyl bromide (1.1 g, 8 mmol) waε added. The mixture was stirred at room temperature for 4 hours, and then partitioned between diethyl ether and water. The ethereal εolution waε dried over magneεium εulfate, fil¬ tered and the filtrate evaporated under reduced preεεure. The reεidue was further purified by flash column chromatography on silica gel to give the title compound (0.7 g) as a waxy εolid. The εtructure waε confirmed by infra-red εpectroεcopy, maεε εpectrometry and nuclear magnetic reεonance εpectroεcopy.

EXAMPLE 12

ethyl 2-[l-(2',6'-dichloro-4'-trifluoromethylphenyl)indol- 6-yloxylacetate

(Compound 54 in Table 1)

1-(2' ,6'-dichloro-4'-trifluoromethylphenyl)-6-hydr- oxyindole (3.5 g, 10 mmol) and potaεsiu carbonate (3.6 g, 26 mmol) were εtirred together in N,N-dimethyIformamide (50 ml) for 30 minutes, and then ethyl bromoacetate (1.5 g, 10 mmol) waε added. The mixture was stirred at room temperature for 18 hours, and then partitioned between diethyl ether and water. The ethereal solution was dried over magnesium sulfate,

filtered and the filtrate evaporated under reduced preεεure to give the title compound (3.0 g) aε a waxy εolid. The εtruc¬ ture waε confirmed by infra-red εpectroscopy, mass εpectro- metry and nuclear magnetic resonance εpectroεcopy.

EXAMPLE 13

2-[l-(2',6'-dichloro-4'-trifluoromethylphenyl)indol- 6-yloxV)acetic acid

(Compound 57 in Table 1)

Sodium hydroxide (4% aqueouε solution, 50 ml) was added to a εolution of ethyl 2-[l-(2',6'-dichloro-4'-trifluoro¬ methylphenyl)indol-6-yloxy]acetate (3.0 g, 6.9 mmol) in iεo¬ propanol (50 ml) and the mixture stirred for 5 minutes at room temperature. The iεopropanol waε removed by evaporation in vacuo, and the remaining aqueouε solution acidified with 2N aqueouε hydrochloric acid and extracted with diethyl ether. The ethereal εolution waε dried over magnesium sulfate, fil¬ tered and the filtrate evaporated under reduced pressure. The residue was further purified by flash column chromatography on εilica gel to give the title compound (1.0 g) aε a colorleεε εolid, m.p. 120-123 ^β C. The εtructure waε confirmed by infra- -red εpectroscopy, asε εpectrometry and nuclear magnetic resonance εpectroεcopy.

EXAMPLE 14

2-[1-(2',6'-dichloro-4'-trifluoromethylphenyl)indol- 6-yloxy]acetamide

(Compound 62 in Table 1)

Oxalyl chloride (0.8 ml, 9 mmol) waε added to a mixture of 2-[l-(2' ,6'-dichloro-4'-trifluoromethylphenyl)indol- -6-yloxy]a cetic acid (1.7 g, 4 mmol) and N,N-dimethyIform¬ amide (1 drop) in dichloromethane (25 ml) and the mixture εtirred at room temperature for 18 hourε. The solvent was

evaporated in vacuo and the residue taken up in diethyl ether.

Ammonium hydroxide (aqueouε solution, specific gravity 0.898,

20 ml) was added, and the mixture εtirred vigorously for one hour. The mixture waε poured into water and extracted with ethyl acetate. The organic extractε were combined, dried over magnesium εulfate, filtered and the filtrate evaporated under reduced preεεure to give the title compound (1.3 g) aε a pale yellow εolid, m.p. 72-75°C.

EXAMPLE 15

1-(3'-dichloro-5'-trifluoromethylpyridin-2-y1)-4-cvanoind ole

(Compound 61 in Table 1)

Step 1

N,N-DimethyIformamide dimethyl acetal (26.3 ml, 198 mmol) and pyrrolidine (6.9 ml, 83 mmol) were added to a εolu¬ tion of 2-cyano-6-nitrotoluene (10.8 g, 66 mmol) in N,N-di- methylformamide (200 ml) , and the mixture heated to 105°C for 3 hourε under an atmoεphere of nitrogen. The mixture was cooled to room temperature and partitioned between water and diethyl ether. The ethereal εolution waε dried over magneεium εulfate, filtered and the filtrate evaporated under reduced pressure to give a deep-red oil (10.6 g) used without further purification in the next step.

Step 2

The product from Step 1 waε disεolved in ethyl acetate (150 ml) and 10% palladium on carbon (1.0 g) added. The mixture waε εtirred under an atmosphere of hydrogen at 40 p.s.i. for 2 hourε. The catalyεt waε removed by filtration, then the filtrate evaporated and the reεidue further purified by flaεh column chromatography on εilica gel to give 4-cyano- indole (4.0 g) aε a yellow εolid m.p. 115-116°C.

Step 3

4-Cyanoindole (4.0 g, 28 mmol) and potassium hydro¬ xide (6.3 g, 112 mmol) were εtirred together in dimethyl sul- foxide (60 ml) at room temperature for 10 minutes, and then 2,3-dichloro-5-trifluoromethylpyridine (4.0 g, 18 mmol) waε added εlowly. The mixture waε εtirred at room temperature for 18 hourε, and then partitioned between diethyl ether and water. The ethereal εolution waε dried over magneεium εul¬ fate, filtered and the filtrate evaporated in vacuo to give a yellow εolid reεidue (6.3 g) . Further purification by flaεh column chromatography on εilica gel gave l-(3'-chloro-5'-tri- fluoromethylpyridin-2-yl)-4-cyanoindole (5.3 g) aε. a pale yellow εolid, m.p. 109-111 ^C C.

EXAMPLE 16

4-amino-l-(3'-chloro-5'-trifluoromethylpyridin-2-yl- indole

(Compound 78 in Table 1.

Step 1

N,N-DimethyIformamide dimethyl acetal (61 ml, 460 mmol) and pyrrolidine (15.9 ml, 190 mmol) were added to a εolution of 2,6-dinitrotoluene (25.0 g, 140 mmol) in N,N-di- methylfor amide (200 ml) , and the mixture heated to 120°C for 30 minuteε under an atmoεphere of nitrogen. The mixture waε cooled to room temperature and partitioned between water and diethyl ether. The ethereal εolution waε dried over magneεium εulfate, filtered and the filtrate evaporated under reduced preεεure to give a deep-red oil (18.5 g) uεed without further- purification in the next εtep.

Step 2

The product from Step 1 was disεolved in ethyl acetate (200 ml) and 10% palladium on carbon (1.8 g) added. The mixture was εtirred under an atmoεphere of hydrogen at 40

_ _

p.ε.i. for one hour. The catalyεt waε removed by filtration, then the filtrate evaporated and the reεidue further purified by flaεh column chromatography on εilica gel to give 4-amino- indole (5.8 g) aε a dark amorphouε εolid.

Step 3

4-Aminoindole (5.8 g, 44 mmol) and sodium hydride (80% diεperεion in mineral oil, 1.3 g, 44 mmol) were stirred together in N,N-dimethylformamide (60 ml), with ice-bath cooling for 5 minuteε, and then 2,3-dichloro-5-trifluoromethy1 pyridine (5,8 g, 44 mmol) waε added εlowly. The mixture waε εtirred at room temperature for 18 hourε, and then a small quantity of methanol was added. The mixture was partitioned between diethyl ether and water. The ethereal εolution waε dried over magneεium εulfate, filtered and the filtrate evapo¬ rated in vacuo to give 4-amino-l-(3'chloro-5'-trifluoromethyl- pyridin-2-yl)indole (6.5 g) aε a dark εolid.

EXAMPLE 17

4-acetamido-l-(3'-chloro-5'-trifluoromethylpyridin-2-yl)i n- dole

(Compound 80 in Table 1)

Acetic anhydride (1.3 g, 13 mmol) was added to a cooled (ice-bath) εolution of 4-amino-l-(3'-chloro-5'-tri- fluoromethylpyridin-2-yl)indole (2.0 g, 6.4 mmol) in dichloro- methane (50 ml) , and the mixture εtirred at room temperature overnight. The precipitate waε collected by filtration, and waεhed with hexane to give the title compound (1.5 g) aε a pink-colored εolid, m.p. 208°C.

EXAMPLE 18

4-azido-l-(3 '-chloro-5'-trifluoromethylpyridin-2-yl .indole

(Compound 87 in Table 1)

4-Amino-l-(3'-chloro-5'-trifluoromethylpyridin-2-yl)- indole (1.7 g, 5 mmol) waε diεεolved in 80% aqueouε acetic acid (100 ml) , and the mixture cooled to 0 ^β C in an ice-εalt bath. A εolution of εodium nitrite (0.4 g, 6 mmol) in water (1 ml) waε added dropwiεe, and once the addition waε complete the mixture waε εtirred for 5 minuteε. A εolution of εodium azide (0.4 g, 6 mmol) in water (1 ml) waε added, and εtirring continued for one hour. The acetic acid waε removed in vacuo, and the reεidue partitioned between water and diethyl ether. The ethereal extract waε waεhed with εaturated aqueouε εodium bicarbonate εolution, dried over magneεium εulfate, filtered and the filtrate evaporated under reduced preεεure to give the title compound (l.l g) aε a pale brown εolid, m.p. 93-95°C.

EXAMPLE 19

3-chloro-l-(3'-chloro-5'-trifluoromethylpyridin-2-yl)- 4-methoxyindole _:

(Compound 63 in Table 1)

Sulfuryl chloride (0.4 g, 3 mmol) waε added to a cooled (ice-bath) εolution of 1-(3'-chloro-5'-trifluoromethy1- pyridin-2-yl)-4-methoxyindole (1.0 g, 3 mmol) in diethyl ether (25 ml) and once the addition was complete, the cooling bath was removed, and the mixture stirred for 18 hours. A further quantity of sulfuryl chloride (0.04 g, 0.3 mmol) waε added, and the mixture heated under reflux for 3 hourε. The mixture waε cooled, waεhed twice with water, dried over magnesium sul¬ fate, filtered and the filtrate evaporated in vacuo. Further purification by flash column chromatography on silica gel gave the title compound (0.6 g) as a yellow waxy solid. The εtruc¬ ture was confirmed by infra-red εpectroεcopy, mass spectro- etry and nuclear magnetic reεonance εpectroεcopy.

Compound 60, l-(3'chloro-5'-trifluoromethylpyridin- 2-yl)2,3-dichloro-4-methoxyindole, m.p. 140-142 ^β C, may be prepared in an analogous fashion, using excess εulfuryl chloride.

The following Table I depictε repreεentative com- poundε of thiε invention:

TABLE I

COMPOUNDS

CF ₃ Oil

Semi-solid

^CF 3 CF ₃ Oil

CF ₃ Semi-solid

CF, Semi-solid.

CF ₃ Semi-solid

CF ₃ Semi-solid

CF ₃ 98.0-100.0 ^β C

CF ₃ Semi-solid

CF, Semi-solid

CF ₃ Oil

CF ₃ Oil

CF ₃ 143.0-148.0 ^β C

CF, Semi-solid

CF ₃ Semi-solid

65.0-70.0 ^β C

^CF 3 CF ₃ Semi-solid

CF ₃ Semi-solid

CF ₃ Semi-solid

CF ₃ Semi-solid

CF ₃ 83.0-84.0 ^β C

CF ₃ Semi-solid

CF ₃ Semi-solid

CF ₃ 65.0-70.0°C

CF ₃ 83.0-85.0 ^β C

CF. Semi-solid

CF, Oil

CF. Semi-solid

CF. no.o-ιi5.o c

CF. Semi-solid

CF. 155.0-158.0°C

CF. Oil

58 6-NHC-C-OC.H. N 3-C1 H CF. 113.0-120.0°C

. . ^{2 5}

59 6-NH ^C -N- ^S0 ₂ - 3-C1 H CF. 160.0-170.0 ^β C

74 6-OS0 ₂ CH ₃ N 3-C1 H CF, Semi-solid 75 4-C-OCH. N 3-C1 H CF. 105.0-107.0 ^β C II ³ 0

76 4-C-OCH, C-Cl 6-C1 H CF. Semi-solid li -

0

77 4-C-OH C-Cl 6-C1 H CF. 222.0-224.0 C

.

78 4-NH ₂ N 3-C1 H CF, Semi-solid 79 4-NHC-CH-, N 3-C1 H CF. 208.0°C

80 N 3-C1 H CF. Semi-solid

81 N 3-C1 H CF. Semi-solid

82 CF ₃ Oil 83 CF ₃ Oil 84 CF, 80.0-82.0 ^β C 85 CF ₃ 85.0 ^β C 86 CF ₃ Oil 87 CF, 95-95 ^β C 88 CF. 190 ^β C

Herbicidal Screening Teεtε

The compoundε liεted in the foregoing table were tested for herbicidal activity by various methods and at various rates of application. The resultε of εome of theεe tests are given below. As one skilled in the art iε aware, the results obtained in herbicidal screening testε are affected by a number of factorε that are not readily control¬ lable. Environmental conditions, such aε amount of sunlight . and water, εoil type, εoil pH, temperature and humidity, are exampleε of εuch factorε. Other factorε which can affect teεt reεultε are the depth of planting and the application rate of the herbicide, as well as the nature of the cropε being tested. Reεultε will alεo vary from crop to crop and within the crop varieties.

PRE-EMERGENCE HERBICIDAL SCREENING TEST

On the day preceding treatment, εeedε of εeveral dif¬ ferent weed εpecieε were planted in εandy loam εoil in individual rowε uεing one εpecieε per row acroεε the width of a flat. The graεεy weedε planted were green foxtail (Setaria viridiε) , wild oat (Avena fatua, , and watergraεε (Echinochloa cruεσalli.. Broadleaf weedε utilized were wild uεtard (Braεsica Jaber) , velvetleaf (AbutiIon theophrasti) , and annual morningglory (Ipomoea purpurea) . Additionally, seeded waε yellow nutεedge .Cyperuε eεculentuε) . Ample seedε were planted to give about 20 to 40 εeedlingε per row, after emer¬ gence, depending upon the εize of the plantε.

Solutions of the test compoundε were made by weighing out 400 mg of the teεt compound into a 60 ml wide-mouth bottle, then disεolving the compound in 25 ml acetone con¬ taining 1% T EEN 20 (polyoxyethylene εorbitan monolaurate emulεifier) . Additional εolventε, not exceeding 5 ml, were uεed if needed to diεεolve the compound. A 20.5 ml aliquot waε then taken from the εolution and diluted with 25 ml of an acetone:water mixture (19:1) containing 1% TWEEN 20 to form a εprayable εolution.

The flats were placed in a greenhouεe at 21-29.5°C, and watered by εprinkling. One day after planting, the flats were εprayed with the εpray εolution calibrated to deliver 00L/ha. The application rate waε 4.0 kg/ha.

The flats were then returned to the greenhouεe and water daily by εprinkling. The degree of weed control waε eεtimated and recorded 3 weeks after treatment, as percentage control compared to the growth of the same specieε in an untreated check flat of the εame age.

The percent control iε the total injury to the plants due to all factorε, including inhibited germination, killing of the plant tisεue after emergence, εtunting, malformation,

chloroεiε and other types of injury. The control ratingε vary from 0 to 100 percent, where 0 repreεentε no effect with growth equal to the untreated control, and 100 repreεentε complete kill; a daεh indicateε that no teεt waε performed at that level of application.

POST-EMERGENCE HERBICIDAL EVALUATION

The εoil waε prepared and seeded with the same vari¬ eties as described for the pre-emergence test. The flatε were placed in the greenhouεe at 21-29°C and watered by εprinkling. The εeedε of the weed εpecieε were planted 10 - 12 dayε before treatment. The flatε were εprayed with εolution at a rate of 4 kg/ha, uεing a εpray εolution aε prepared in the pre-emer¬ gence teεt.

The flatε were returned to the greenhouεe after εpraying and watered daily without wetting the foliage. Three weekε after treatment the degree of weed control waε eεtimated and recorded aε percentage control compared to the growth of the εame εpecieε in an untreated check flat of the εame age. The percent control ratings were aεεigned on the baεiε aε for the pre-emergence evaluation.

Table II liεtε the reεultε of theεe teεtε, in terms of averages for the grasses and broadleaf weedε, with yellow nutεedge liεted εeparately, in both pre- and poεt- emergence evaluationε.

TABLE II

Pre-emergence Herbicidal Activity Application Rate - 4.0 kg/ha

Abbreviationε: AVG: Graεε weedε averaged

AVB: Broadleaf weedε averaged YNS: Yellow Nutεedge

33

34

35

36

37

38

39

40

41

42

60

61

63

64

68

72

73

78

79

80

81

82

In the following Table III, plants were treated eεεentially the εame as plants in Table II, however, the flatε were sprayed with a solution at a rate of 1 kg/ha. The re¬ εultε depicted in thiε Table do not average the herbicide reεultε. The graεεes and broad leaf weeds are listed εepa- rately for both pre-emergence and poεt-emergence. The weedy εpecieε are abbreviated aε follows: green foxtail, SET; wild- oat, AVF; watergraεε, ECH; mustard, SIN; velvetleaf, ABT; annual morningglory, IPOSS and yellow nutεedge, YNS.

TAB E III

The compounds of the preεent invention are uεeful aε herbicideε and can be applied in a variety of wayε known to thoεe εkilled in the art, at variouε concentrationε. In practice, the compounds are applied aε formulations containing the various adjuvants and carriers known to or used in the induεtry for facilitating diεperεion. The choice of formu¬ lation and mode of application for any given compound may affect itε activity, and εelection will be made accordingly. The compoundε of the invention may thuε be formulated aε gran- uleε, aε wettable powders, as emulεifiable concentrateε, aε powders or dustε, aε flowables, aε εolutions, suεpensions or emulsionε, or in controlled-releaεe formε εuch aε micro- capεuleε. Theεe formulationε may contain aε little aε about 0.5% to aε much aε amount 95% or more by weight of active ingredient. The optimum amount for any given compound will

depend upon the nature of the seeds or plantε to be con¬ trolled. The rate of application will generally vary from about 0.01 to about 10 poundε per acre, preferably from about 0.02 to about 4 poundε per acre.

Wettable powderε are in the form of finely divided particleε which diεperεe readily in water or other liquid car- rierε. The particleε contain the active ingredient retained in a εolid matrix. Typical εolid matriceε include fuller'ε earth, kaolin clayε, εilicaε and other readily wet organic or inorganic εolidε. wettable powderε normally contain about 5% to about 95% of the active ingredient pluε a small amount of wetting, diεperεing, or emulεifying agent.

Emulsifiable concentrateε are homogeneouε liquid compoεitionε diεperεible in water or other liquid, and may conεiεt entirely of the active compound with a liquid or εolid emulεifying agent, or may alεo contain a liquid carrier, εuch aε xylene, heavy aromatic naphthaε, iεophorone and other non¬ volatile organic εolventε. In uεe, theεe concentrateε are diεperεed in water or other liquid and normally applied aε a εpray to the area to be treated. The amount of active ingre¬ dient may range from about 0.5% to about 95% of the concen¬ trate.

Granular formulationε include both extrudateε and relatively coarse particleε, and are uεually applied without dilution to the area in which εuppreεεion of vegetation iε deεired. Typical carrierε for granular formulationε include εand, fuller ^, ε earth, attapulgite clay, bentonite clayε, mont- morillonite clay, vermiculite, perlite and other organic or inorganic materials which abεorb or which can be coated with - the active compound. Granular formulationε normally contain about 5% to about 25% active ingredientε which may include εurface-active agents such as heavy aromatic naphthas, kero¬ sene and other petroleum fractions, or vegetable oilε; and/or εtickerε εuch aε dextrins, glue or synthetic resinε.

Duεtε are free-flowing admixtureε of the active ingredient with finely divided εolidε εuch aε talc, clayε, flourε and other organic and inorganic solids which act aε diεperεantε and carrierε.

Microcapεuleε are typically dropletε or granuleε of the active material encloεed in an inert porouε shell which allows eεcape of the encloεed material to the surroundings at controlled rates. Encapsulated droplets are typically about 1 to 50 microns in diameter. The enclosed liquid typically con¬ stitutes about 50 to 95% of the weight of the capsule, and may include solvent in addition to the active compound. Encapεu- lated granuleε are generally porouε granuleε with porouε mem- braneε εealing the granule pore openingε, retaining the active εpecieε in liquid form inεide the granule poreε. Granuleε typically range from 1 millimeter to 1 centimeter, preferably 1 to 2 millimeterε in diameter. Granuleε are formed by extruεion, agglomeration or prilling, or are naturally occur¬ ring. Exampleε of εuch materialε are vermiculite, εintered clay, kaolin, attapulgite clay, sawdust and granular carbon. Shell or membrane materials include natural and synthetic rubbers, cellulosic materialε, εtyrene-butadiene copolymerε, polyacrylonitrileε, polyacrylateε, polyeεters, polyamideε, polyureaε, polyurethaneε and εtarch xanthateε.

Other uεeful formulations for herbicidal appli¬ cations include simple solutionε of the active ingredient in a εolvent in which it iε completely εoluble at the deεired con¬ centration, εuch aε acetone, alkylated naphthaleneε, xylene and other organic εolventε. Preεεurized sprayers, wherein the active ingredient is diεperεed in finely-divided form aε a reεult of vaporization of a low boiling diεperεant εolvent carrier, εuch aε the Freonε, may alεo be uεed.

Many of theεe formulations include wetting, disperε- ing or emulεifying agentε. Exampleε are alkyl and alkylaryl εulfonateε and εulfateε and their εaltε; polyhydric alcoholε; polyethoxylated alcoholε; eεterε and fatty amineε. Theεe agentε when used normally comprise from 0.1% to 15% by weight of the formulation.

The compoundε of the preεent invention are also use¬ ful when combined with other herbicides and/or defoliants, deεεicantε, growth inhibitorε, and the like. Theεe other materialε can compriεe from about 5% to about 95% of the active ingredientε in the formulationε. Theεe combinationε frequently provide a higher level of effectiveneεε in control¬ ling weedε and often provide reεultε unattainable with sepa¬ rate formulations of the individual herbicides.

Examples of other herbicides, defoliants, desεicantε and plant growth inhibitorε with which the compoundε of thiε invention can be combined are:

acetanilide herbicides such as alachlor, 2-chloro-2' ,6'- diethyl-N-(methoxymethyl) acetanilide; acetochlor, 2-chloro- N(ethoxymethyl)-6'-ethyl-o-acetotoluidide; metolachlor, 2- chloro-2'-methyl-6'ethyl-N-methoxyiεopropyl-2-acetanilide;

chlorophenoxy herbicideε εuch aε 2,4-D, 2,4,5-T, MCPA, MCPB, 2,4-DB, 2,4-DEB, 4-CPA, 2,4,5-TB, and εilvex;

carbamate herbicides such as propham, chlorpropham, swep, and barban;

thiocarbamate and dithiocarbamate herbicideε εuch aε CDEC, metham-sodium, EPTC, diallate, PEBC, and vernolate;

subεtituted urea herbicideε εuch aε norea, dichloral, urea, chloroxuron, cycluron, fenuron, monuron, monuron TCA, diuron, linuron, monolinuron neburon, buturon and trimeturon;

εymmetrical triazine herbicideε εuch aε εimazine, chlorazine, deεmetryne, norazine, ipazine, prometryn, atrazine, trieta- zine, εimetone, prometone, propazine and ametryne;

chlorinated aliphatic acid herbicideε such aε TCA and dalapon;

chlorinated benzoic acid and phenylacetic acid herbicides such aε 2,3,6-TBA, dicamba, tricamba, chloramben, fenac, PBA, 2- methoxy-3,6-dichlorophenyl acetic acid, 3-βethoxy-2,6-di- chlorophenyl acetic acid, 2-methoxy-3,5,6-trichlorophenyl acetic acid, and 2,4-dichloro-3-nitro benzoic acid;

and εuch compounds aε aminotriazole, aleic hydrazide, phenyl- mercury acetate, endothal, technical chlordane, CDCPA, diquat, erbon, DNC, DNBP, dichlobenil, DPA, diphena ide, dipropalin, trifluralin, εolan, dicryl, merphoε, DMPA, DSMA, MSMA, potaε- εium azide, acrolein, benefin, benεulide, AMS, bromacil, 2-(3,4-dichlorophenyl)-4-methyl-l,2,4-oxazolidine-3 ,5-dione, bromoxynil, cacodylic acid, CMA, CPMF, cypromid, DCB, DCPA, dichlone, diphenatril, DMTT, DNAP, EBEP, EXD, HCA, ioxynil, IPX, iεocil, potaεεium cyanate, MAA, MAMA, MCPES, MCPP, MH, molinate, NPA, OCH, paraquat; PCP, piclorari, DPA, PCA, sesone, terbacil, terbutol, TCBA, nitralin, sodium tetraborate, cal¬ cium cyanamide, S,S,S-tributylphosphorotrithioate and pro- panil, iεopropyl amine εalt of N-phoεphonomethyl glycine, tri- methylεulfonium εaltε of N-phoεphonomethyl glycine.

Theεe formulationε can be applied to the areas where control iε deεired by conventional methods.. Duεt and liquid compoεitionε, for example, can be applied by the uεe of power- duεterε, boom and hand εprayerε and εpray duεterε. The formu¬ lationε can alεo be applied from airplanes aε a duεt or a εpray or by rope wick applicationε. To modify or control growth of germinating εeedε or emerging εeedlingε, duεt and liquid formulationε can be diεtributed in the εoil to a depth of at leaεt one-half inch below the εoil εurface or applied to the εoil εurface only, by εpraying or εprinkling. The formu¬ lationε can alεo be applied by addition to irrigation water. - Thiε permitε penetration of the formulationε into the soil together with the irrigation water. Dust compoεitionε, granu¬ lar compoεitionε or liquid formulationε applied to the surface of the εoil can be diεtributed below the εurface of the soil by conventional means such as discing, dragging or mixing operations.

The following are exampleε of typical formulationε:

5% duεt: 5 partε active compound

95 partε talc

2% duεt 2 partε active compound

1 part highly diεperεed εilicic acid 97 partε talc

Theεe duεtε are formed by mixing the componentε then grinding the mixture to the deεired particle size.

5% granules: 5 parts active compound

0.25 part epichlorohydrin 0.25 part cetyl polyglycol ether 3.5 parts polyethylene glycol 91 part kaolin (particle size 0.3-0.8 mm)

Granules are formed by mixing the active compound with epichlorohydrin and disεolving the mixture in 6 partε of acetone. The polyethylene glycol and cetyl polyglycol ether are then added. The reεultant solution iε εprayed on the kaolin and the acetone evaporated in vacuo.

Wettable powderε:

70%: 70 partε active compound

5 partε εodium dibutylnaphthylεulfonate 3 partε naphthaleneεulfonic acid/phenolεulfonic acid/formaldehyde condenεate (3:2:1) 10 partε kaolin 12 partε Champagne chalk

40%: 40 partε active compound

5 partε εodium lignin εulfonate 1 part εodium dibutylnaphthalene εulfonic acid 54 partε εilicic acid ,

25%: 25 partε active compound

4.5 partε calcium lignin εulfate

1.9 partε Champagne chalk/hydroxyethyl celluloεe (1:1) 1.5 partε εodium dibutylnaphthalene εulfonate 19.5 εilicic acid 19.5 partε Champagne chalk 28.1 partε kaolin

25%: 25 partε active compound

2.5 partε iεooctylphenoxy-polyethylene- ethanol 1.7 partε Champagne chalk/hydroxyethyl celluloεe (1:1) 8.3 partε sodium aluminum silicate 16.5 parts kieselguhr 46 partε kaolin

10%: 10 partε active compound

3 partε of a mixture of εodium εaltε of εaturated fatty alcohol εulfateε 5 partε naphthaleneεulfonic acid/ formaldehyde condensate 82 parts kaolin

These wettable powders are prepared by intimately mixing the active compoundε with the additives in suitable mixers, and grinding the resulting mixture in mills or rollers.

Emulεifiable concentrate:

25%: 25 partε active subεtance

2.5 parts epoxidized vegetable oil 10 parts of an alkylarylεulfonate/fatty alcohol polyglycol ether mixture 5 partε dimethylformamide 57.5 partε xylene