PHENOXYPHENYD-3-BENZOYL UREA COMPOUNDS

AND PROCESS FOR PREPARATION

This application is a continuation-in-part of U.S. Patent Application Serial No. 495,331, filed Hay 20. 1983. which is a continuation-in-part of U.S. Patent Application Serial No. 393.553. filed June 30, 1982.

Brief Summary of the Invention

Technical Field

This invention relates to novel l-(4-phenoxyphenyl)-3-benzoyl urea compounds which are useful as the active toxicant in pesticidal compositions. This invention also relates to a method for the preparation of the novel l-(4-phenoxyphenyl)-3-benzoyl urea compounds. This invention further relates to pesticidal compositions and to a method for their use.

Background of the Invention

In recent years a variety of benzoyl urea compounds have been reported in the literature as having pesticidal activity. For example, benzoylureido-diphenyl ethers and their use as insecticides have been disclosed in U.S. Patent 4,005.223 issued January 25, 1977, U.S. Patent 4,041,177 issued August 9. 1977. and U.S. Patent 4,068,002 issued January 10, 1978. Also, N-benzoyl- N'-phenoxyphenyl urea compounds and their use as insecticides have been disclosed in U.S. Patent 4.399.152 issued August 16, 1983, Japanese Patent

Application 5 5038 357 published March 17. 1980. Japanese Patent Application 5 6092 857 published July 27, 1981. and- Japanese Patent Application 5 7002 258 published January 7. 1982.

N-benzoyl-N'-phenoxypyridyl urea compounds have been disclosed in European Patent No. 0069288 issued January 12, 1983.

Accordingly, one or more of the following objects will be achieved by the practice of this invention. It is an object of this invention to provide novel l-(4-phenoxyphenyl)-3-benzoyl urea compounds. Another object of this invention is to provide certain l-(4-phenoxyphenyl)-3-benzoyl urea compounds which exhibit excellent insecticidal activity. A still further object of this invention is to provide novel benzoyl urea compounds, such as l-[2,3-dichloro-4-(2.4-dichlorophenoxy)-6- methylphenyl]-3-(2,6-difluorobenzoyl) urea, l-[2,3-dichloro-4-(2-bromo-4-chlorophenoxy)-6-methyl- phenyl]-3-(2,6-difluorobenzoyl) urea, l-[4-(2.4-dichlorophenoxy)-2,3.6-trimethyl- phenyl]-3-(2,6-difluorobenzoyl) urea, etc. Another object is to provide processes for the preparation of the novel benzoyl urea compounds. A further object is to provide novel pesticidal compositions containing the novel benzoyl urea compounds as the active toxicant. Another object of the invention is to provide a method for controlling pests by the application of the novel pesticidal compositions. These and other objects will readily become apparent to those skilled in the art in the light of the teachings herein set forth.

Disclosure of the Invention

In its broad aspect the invention relates to novel l-(4-phenoxyphenyl)-3-benzoyl urea compounds, pesticidal compositions containing the same, and processes for their preparation and use. The benzoyl urea compounds of this invention can be represented by the following formula:

FORMULA (1)

wherein:

X represents halogen;

X ^I represents hydrogen or halogen;

X' ¹ represents fluorine or hydrogen with the proviso that when X ¹ is halogen then X' ' is hydrogen;

R , R and R are independently methyl, chlorine or bromine with the proviso that one of R and R is other than chlorine or bromine;

R represents methyl, chlorine, fluorine or bromine; and

R' , R' ¹ and R' ^{1 1} are independently hydrogen, methyl, chlorine, fluorine or bromine provided that at least one of R' , R' ' and R' ¹ ' is other than hydrogen.

Detailed Description

As indicated above, the invention relates to novel l-(4-phenoxyphenyl)-3-benzoyl urea compounds, pesticidal compositions containing the same, and processes for their preparation and use.

Preferred benzoyl urea compounds within the broad generic Formula (1) are those having the formulas:

wherein X. X'. R . R . R . R. R'. R' ' and R' ' '

-i. -fa are as indicated above.

Particularly preferred benzoyl urea compounds are those of the formulas:

where in X . X ' . R . R . R . R and ar e as indicated above ; and

wherein X. X'. R. and R' ' are as indicated above.

The following benzoyl urea compounds listed in Tables A through G are illustrative of those encompassed by the above formulas and which can be prepared by the practice of this invention:

Table A

Eβpresentative l-(4-Phenoχyphenyl)-3-

Benzoyl Urea Compounds

F F Cl Cl

Cl H Cl Cl

F Cl Cl Cl

Cl Cl Cl Cl

Br F Cl Cl

Table A (Continued)

Representative l-(4-Phenoχyphenyl)-3-

Benzoyl Urea Compounds

R

Cl Br Cl Cl

H F Cl Cl

Br H Cl Cl

F F Br Cl

F H Br Cl.

H Cl Br Cl

Cl Cl Br Cl

Cl F Br Cl

F F Br Br

H F Br Br

Cϊ Cl Br Br

Cl Br Br Br

Cl F Br Br

F F CH ₃ CH ₃

Cl H CH ₃ CH ₃

H F CH CH 3 3

Cl F CH CH ₃

Cl Cl CH ₃ CH 3

F F Br CH 3

F F CH Br

F F Cl CH

F F CH ₃ Cl

F F F Cl

F F F Cl

H F F F

Cl H F F

F F F F

Table A (Continued)

Representative l-(4-Phenoχyphenyl)-3-

Benzoyl Urea Compounds

R

Cl H Cl F

F F Cl F

H Cl F Br

F F F Br

F F Br F

Table B

Representative l-(4-Phenoχyphenyl)-3-

Benzoyl Urea Compounds

X X' R R' ' R' ' '

F F Cl H Cl

Cl H Cl H Cl

F • H Cl H Cl

H ^' F Cl Cl Cl

H Cl Cl Cl Cl

F F Cl Cl Cl

H Cl Cl Br Cl

F H * Cl Br Cl

F F Cl Br Cl

F F Br Cl Cl .

Cl H Br Cl Cl

Cl F Br Cl Cl

F H Br Cl Cl

Cl F Br CH ₃ Cl

F F Br CH ₃ Cl

Cl H Br CH ₃ Cl

F F CH CH_ CH

Cl F CH. CH. CH.

F H ^CH . CH ^* CH.

F Cl ^"

H Cl ^CH . Cl Ct

F H _CH ; Cl CH ^"

F F Cl Cl ^"

H Cl CH. Cl Cl

Table B (Continued)

Representative l-(4-Phenoxyphenyl)-3-

Benzoyl Urea Compounds

R

F H CH Cl Cl

F F CH ₃ Br Cl

Cl F CH ₃ Br Cl

Cl Cl CH Br Cl

•_?

Cl H Br Br CH ₃

F H Br Br CH 3

F F Br Br CH ₃

F H Br Cl Br

Cl H Br Cl Br

F F Br Cl Br

F F CH ₃ F CH ₃

F F CH ₃ CH ₃ F

F F Cl F Cl

F F CH ₃ H CH ₃

F Cl CH ₃ H

^CH 3

F H CH H CH ₃

Cl H CH. CH. CH ₃

t o

Table C

E {epresentative l-( 4-Phenoxyphen 1)- ^■ 3-

Benzoyl Urea Compounds

X X' R R' ' R' ' '

F F Cl Cl H

H Cl Cl Cl H

F H Cl Cl H

Cl F Cl Cl H

Cl Cl Cl Cl H

F F Br Cl H

H Cl Br Cl H

Cl F Br Cl H

F H Br Cl H

Cl Cl Br Cl H

F F Br Br H

Cl H Br Br H

H F Br Br H

F H Cl H Cl

F F Cl H Cl

Cl F Cl H Cl

F F Br H Cl

F H Br H Cl

Cl H Br H Cl

F F Cl Cl Cl

Cl F Cl Cl Cl

F H Cl Cl Cl

F F CH ₃ Cl ^CH 3

Cl w CH, Cl CH,

Table C (Continued)

Representative l-(4-Phenoχyphenyl)-3-

Benzoyl Urea Compounds

R'

F H ^CH 3 Cl CH ₃

F F CH ₃ CH ₃ CH ₃

H Cl CH ₃ CH ₃ CH ₃

F H CH ₃ CH CH

3 3

F F CH ₃ Cl Cl

H F CH ₃ Cl Cl

Cl H CH ₃ CH ₃ H

F F CH ₃ H CH ₃

Cl H CH ₃ H CH ₃

Tablie D

Representative 1 -(4 -Phenoxyphenyl)- 3-

Benzoyl Ureaι Compound.

X X' R R' ' R' ' '

F F ^' Cl Cl H

H F Cl Cl H

Cl H Cl Cl H

Cl F Cl Cl H

Cl Cl Cl Cl H

F F Br Cl H

F H Br Cl H

F Cl Br Cl H

Cl Cl Br Cl H

F Cl Br Cl H

F F Br Br H

H F Br Br H

Cl H Br Br H

F F Cl H Cl

F Cl Cl H Cl

C H Cl H Cl

F F CH ₃ Cl CH ₃

F H CH ₃ Cl CH 3

H Cl CH ₃ Cl CH 3

F F CH ₃ CH ₃ CH 3

Cl H CH ₃ CH ₃ CH

•J

F H CH ₃ CH ₃ CH 3

F F CH ₃ Br CH ₃

Cl H CH, Br CH,

Table D (Continued)

Representative l-(4-Phenoχyphenyl)-3-

Benzoyl Urea Compounds

R ¹

F F Br Br Br

Cl H Br Br Br

H Cl CH ₃ Cl Cl

F F CH ₃ Cl Cl

F F CH ₃ H CH ₃

H Cl CH ₃ H CH ₃

H Cl CH ₃ CH ₃ H

F F CH ₃ CH H 3

Table E

Representative 1 L- (4-Phenoxyphenyl)- -3-

X X' R R' ' R' ' '

F F Cl Cl H

Cl F Cl Cl H

H F Cl Cl H

Cl H Cl Cl H

Cl Cl Cl Cl H

F F Br Cl H

F Cl Br Cl H

F H Br Cl H

Cl H Br Cl H

Cl Cl Br Cl H

F F Br Br H

Cl F Br Br H

Cl H Br Br H

H F Br 3r H

F F CH ₃ CH ₃ H

Cl H CH ₃ CH ₃ H

Cl F Cl H Cl

F F Cl H Cl

Cl H Cl H Cl

Cl H CH ₃ H CH

F F CH ₃ H CH ₃

H F CH H CH

F F Cl Cl Cl

H F Cl Cl Cl

Table E (Continued)

Representative l-(4-Phenoχyphenyl)-3-

Benzoyl Urea Compounds

R

Cl H Cl Cl Cl

F F CH ₃ CH ₃ CH ₃

H F CH ₃ CH ₃ CH ₃

H Cl CH ₃ H ₃ CH ₃

F F CH ₃ Cl H ₃

Ta b le F

Representative l-(4-Phenoχyphenyl)-3-

Benzoyl Urea Compounds

X ' R.

Cl H H CH Cl CH 3 3

F H H CH Cl CH 3 3

F F H CH Cl CH 3 3

Cl F H CH ₃ Cl CH 3

Cl H 4-F CH Cl CH 3 3

Cl H 5-F CH ₃ Cl CH ₃

F F H CH ₃ CH ₃ Cl

F H H CH ₃ CH ₃ Cl

Cl F H CH ₃ CH Cl 3

Cl H H CH CH Cl

Cl H 4-F CH CH Cl 3 3

Cl H 5-F CH CH CH 3 3 3

F F H Cl Cl CH

Cl H 4-F Cl Cl CH ₃

Cl H 5-F Cl Cl CH ₃

Cl F H Cl Cl CH

Ta b le G

Representative 1- (4-Phenoχyphenyl )-3-

Benzoyl Urea Compounds

F H CH ₃ Br CH ₃ Cl

Cl H CH Br CH ₃ Cl

3

F F CH Br CH Cl

3 3

F F CH ₃ Br CH Br

3

H Cl CH Br CH Br

3

F H Br CH Br

^CH 3 3

F F ^CH . CH Br Cl

F F CH. Cl Br Br

H Cl CYL] Cl Br Br

The novel benzoyl urea compounds of this invention can be conveniently prepared by one or more methods. For example, the compounds of this invention may be prepared by reacting a substituted phenoxyaniline 2. with a benzoyl isocyanate 3_ according to Scheme I as follows:

organic solvent

Scheme I

wherein X. X'. X ¹ '. R , R _2> R . R, R ¹ , R' ' and R' ¹ ' have the meaning given to Formula (1).

Alternatively. the novel compounds may be prepared by the reaction of an phenoxyphenyl- isocyanate 4. with a benzamide 5. according to Scheme II as follows:

organic solvent

Scheme I I

wherein X. X'. X' ¹ . R . R . R . R. R', R ¹ ' and R' ¹¹ have the meaning given to Formula (1).

The subject compounds may also be prepared by the reaction of a benzoyl chloride 6. with a substituted urea according to Scheme III as follows:

organic solvent

Scheme III

wherein X. X'. X ¹ '. R^ ₂ » R ₃ , R. R'. R' • and R' ¹ ' have the meaning given to Formula (1).

In general, the reactions illustrated in Schemes I, II and III can be carried out in organic solvents such as aromatic hydrocarbons, halogenated hydrocarbons, ethers and the like. Solvents like toluene. 1,2-dichloroethane, dichloromethane and p-dioxane are preferred. These reactions proceed at temperatures ranging from ambient temperature to 150°C.

The intermediates shown in Schemes I. II and III can be prepared according to generally accepted procedures. Thus, the substituted benzoyl isocyanate 3_ can be prepared from the corresponding benzamide 5. following the general procedure of Speziale et. al., J. Orq. Chem. 2 _. 3742 (1962) as follows:

Scheme IV

wherein X, X' and X ¹ ' have the meaning given in Formula (1) .

The substituted phenoxyanilines 2. for which R and are not chlorine or bromine may be

prepared according to Scheme V involving the reaction of a substituted phenol 9_ with a chloronitrobenzene 8 as follows:

8

10

Scheme V

wherein R , R . R . R. R'. R' ^• and R' ' ' have the meaning given in Formula (l) with the proviso that and R are not chlorine or bromine. The reaction of a substituted phenol 9. with a chloronitrobenzene 8. to give the nitro ether JLO proceeds in the presence of a base in an inert solvent at elevated temperature. Bases suitable for this reaction are potassium carbonate, sodium hydride, potassium hydroxide, and sodium hydroxide. Suitable solvents are toluene, dimethylforma ide, and dimethylsulfoxide. The above transformation can be carried out in a diphasic reaction medium in the presence of a phase-transfer catalyst.

The reduction of nitro ether 10. to phenoxyaniline 2. can be achieved by hydrogenation using a catalytic amount of platinum or palladium on carbon or a Raney Nickel catalyst under an atmosphere of hydrogen at a pressure ranging from 40-200 psi at ambient temperature. Suitable solvents for hydrogenation include aromatic hydrocarbons or alcohols. The reduction can also be achieved by a chemical method using hydrazine and a metal catalyst as disclosed in Chem. Rev.. Vol. 65. pp. 51-68 (1965).

Isocyanate 4. can be obtained by reacting the substituted aniline 2. with phosgene. Urea 1 may be obtained via the reaction of isocyanate 4. with ammonium hydroxide or gaseous ammonia. These reactions are illustrated in Scheme VI below as follows:

Scheme VI

wherein R . R , R , R, R'. R' ¹ and R ^{1 1} ' have the meaning given in Formula (1).

The substituted phenoxyanilines 2. for which R or is chlorine or bromine are obtained upon halogenation of 4-phenoxyanilines 1_1 and 1,2. as

Scheme VII

wherein R = X = chlorine or bromine and R ,

R . R, R', R' ' and R' ' ' have the meaning given in 2

Formula (1) for the transformation of 11 to 2 and wherein R = X = chlorine or bromine and R_. R , R. R*. R" and R' ' ' have the meaning given in Formula (1) for the transformation of 12. to 2.. Suitable solvents for these transformations include aromatic hydrocarbons, such as benzene, or polar protic solvents, such as acetic acid. Halogenation of anilines 1 and .12. may be effected by their exposure to chlorine or bromine in a suitable solvent at low temperature or preferably treatment with a N-halosuccinimide in benzene or acetic acid. Temperatures required for the reaction vary according to the identity of substituents R_, R, and R but generally fall in the range of 20°C- 80°C.

Phenoxyanilines of types i and JL2. are prepared by the ^' method depicted in Scheme V above but where R and R individually may represent hydrogen or methyl.

The 4-chloro-l-nitrobenzenes required in Scheme V and Scheme VII are either commercially available or may be prepared through either a Sandmeyer reaction (Miller et. al., J. Med. Chem. 1980. 23, 1083) starting with known 4-nitro anilines 13 or via a nitration of known chlorobenzenes JL4. as depicted in Scheme VIII below as follows:

13 8

14

Scheme VI I I

An alternate route to phenoxyanilines of type 2., in particular the phenoxyaniline 1_9, is depicted in Scheme IX below as follows:

15 16

wherein R . R , R . R and R" have the meaning given in Formula (1) and R' ¹ is chlorine or bromine. This reaction involves the coupling of an aminophenol 1_5. with a 4-chloronitrobenzene ljj. in the presence of a base to afford 4-nitrophenoxyaniline 12 -as described in Schramm et al., Ann.. 740. 169 (1970). Reaction of the amino group in 12 with trifluoroacetic anhydride affords

23

amide JL8.. Nitro group reduction. Sandmeyer halogenation and deprotection of the amino function afford aniline 1_9. The details of these transformations are given in the experimental section hereinbelow.

Aminophenols of type 1_5 are readily available and may be prepared as illustrated in the elaboration of aminophenol 22_ via nitration of a 3, -disubstituted phenol 0 followed by halogenation and nitro group reduction as depicted in Scheme X below as follows:

HNO.

Halogenation

22

Reduction

23

Scheme X wherein R and R have the meaning given in Formula (1) and Y is bromine or chlorine.- This approach to intermediates 21. and ^2 reflect that described by Albert and Sears. J^_ Am. Chem. Soc.. 76. 4979 (1954).

An alternate and complimentary approach to aminophenols .15. is detailed in Scheme XI as follows:

Θ

24

Reduction

25

OH

15

Scheme XI wherein R., R_ and R ₃ have the meaning given in Formula (1). This involves the reaction of a trisubstituted phenol 2. with a diazonium salt prepared from εulfanilic acid to afford the intermediate diazo compound 25. which is reduced to give aminophenol .15.. The synthetic methodology used in this approach to aminophenol lji. is that described by Payne and Weiden in U.S. Patent 3,752.838.

The compounds contemplated in this invention may be employed as insecticides according to methods known to those skilled in the art. Pesticidal compositions containing the compounds as the active toxicant will usually comprise a carrier and/or diluent, either liquid or solid.

Suitable liquid diluents or carriers include water, petrolium distillates, or other liquid carriers with or without surface active agents. Liquid concentrates may be prepared by dissolving one of these compounds with a nonphytotoxic solvent such as acetone, xylene, nitrobenzene, cyclohexanone or dimethyl formamide and dispersing the toxicants in water with the aid of suitable surface active emulsifying and dispersing agents.

The choice of dispersing and emulsifying agents and the amount employed is dictated by the nature of the composition and the ability of the agent to facilitate the dispersion of the toxicant. Generally, it is desirable to use as little of the agent as is possible, consistent with the desired

dispersion of the toxicant in the spray so that rain does not re-emulsify the toxicant after it is applied to the plant and wash it off the plant. Nonionic. anionic, or cationic dispersing and emulsifying agents may be employed, for example, the condensation products of alkylene oxides with phenol and organic acids, alkyl aryl sulfonates. complex ether alcohols, quaternary ammonium compounds, and the like.

In the preparation of wettable powder or dust or granulated compositions, the active ingredient is dispersed in and on an appropriately divided solid carrier such as clay, talc, bentonite, diatomaceous earth, fullers earth, and the like. In the formulation of the wettable powders the aforementioned dispersing agents as well as lignosulfonates can be included.

The required amount of the toxicants contemplated herein may be applied per acre treated in from 1 to 200 gallons or more of liquid carrier and/or diluent or in from about 5 to 500 pounds of inert solid carrier and/or diluent. The concentration in the liquid concentrate will usually vary from about 10 to 95 percent by weight and in the solid formulations from about 0.5 to about 90 percent by weight. Satisfactory sprays, dusts, or granules for general use contain from about 1/4 to 15 pounds of active toxicant per acre.

The pesticides contemplated herein prevent attack by insects upon plants or other material to which the pesticides are applied, and they have relatively high residual toxicity. With respect to plants, they have a high margin of safety in that

when used in sufficient amount to kill or repel the insects, they do not burn or injure the plant, and they resist weathering which includes wash-off caus ^" ed by rain, decomposition by ultraviolet light, oxidation, or hydrolysis in the presence of moisture or. at least, such decomposition, oxidation, and hydrolysis as would materially decrease the desirable pesticidal characteristic of the toxicants or impart undesirable characteristics, for instance, phytotoxicity, to the toxicants. The toxicants are so chemically inert that they are now compatible with substantially any other constituents of the spray schedule, and they may be used in the soil, upon the seed, or the roots of plants without injuring either the seeds or roots of plants. Mixtures of the active compounds may be employed if desired as well as combinations of the active compounds of this invention with other biologically active compounds or ingredients.

The following examples are illustrative of the methods utilized in the preparation of intermediates and compounds of this invention. For NMR spectroscopic analysis, chemical shifts are reported in parts per million downfield from the internal standard, tetraraethylsilane.

EXAMPLE A Preparation of 4-amino-2.3.5-trimethylphenol

Into a solution of sulfanilic acid (49.4 grams, 258 raraol) in water (258 milliliters) contained in a round bottom reaction flask equipped with a magnetic stirrer. thermometer and ice bath at 15°C was added solid Na-COg (13.68 grams. 129 mmol) followed by a solution of NaNO (19.38 grams. 280 mmol) in water (53 milliters). Into a

separate round bottom reaction flask equiped with magnetic stirrer, thermometer, ice bath and ice (204 grams) was charged concentrated HCl (46 milliliters) and the solution of the diazonium salt prepared above. This mixture was stirred at 15°C for 45 minutes. Meanwhile, a third reaction flask equipped with condenser, nitrogen inlet, thermometer. addition funnel and mechanical stirrer was charged with water (258 milliliters). NaOH (56.8 grams, 142 mmol) and 2,3,5-trimethylphenol (35.3 grams, 259 mmol). This mixture was cooled to 0°C by means of an ice-salt bath and the diazonium salt - HCl mixture prepared above was added dropwise while maintaining the temperature below 5°C. Upon completion of the diazonium salt-HCl mixture addition, the reaction mixture was warmed to 52°C and solid (11.9 grams, 68.3 mmol) was added. Stirring was continued and the mixture heated to 80°C whereupon additional Na S 0

(107.1 grams. 615.13 mmol) was added in three equal portions (35.7 grams. 205.04 mmol) at 5 minute intervals. The mixture was then stirred at 80°C for 20 minutes, cooled to room temperature and filtered to afford a crude product which was dissolved in ethyl acetate and dried over sodium sulfate. This solution was concentrated under reduced pressure and afforded crude 4-amino-2,3.5-trimethylphenol. NMR spectroscopic analysis indicated the following: H'-NMR (CDC1 ): 2.1 (S, 9H) , 4.6 (S. 2H) , 6.49 (S. 1H).

EXAMPLE B

Preparation of 4-f2-chloro-4-nitrophenoχy)-2.3.6-tri- ethylaniline

Into a 500 milliliter round bottom reaction flask equipped with a magnetic stirrer and nitrogen inlet was charged 4-amino-2,3,5-trimethylphenol

(30.0 grams. 175 mmol) prepared in Example A, dimethylsulfoxide (110 milliters),

3.4-dichloronitrobenzene (28.0 grams. 146 mmol) and potassium t-butoxide (18.1 grams. 161 mmol). The reaction mixture was stirred at room temperature overnight and then diluted with toluene. The organic layer was washed with water (1.5 liters). saturated NH,C1 (200 milliliters) and with 2.5% 4

NaOH until the aqueous layer remained almost colorless. The organic layer was then washed with brine, dried over Na„5C_> , and concentrated under

2 4 reduced pressure to afford a crude product of 4-(2-chloro-4-nitrophenoxy)-2,3,6- trimethylaniline as a brown oil (11.5 grams). NMR spectroscopic analysis indicated the following: H'-NMR (CDC1 ) : 8.36 (d. J = 2 Hz. 1H). 8.0 (d. d; J = 2. 9 Hz; 1H) , 6.73 (S. 1H). 6.63 (d. J = 9 Hz. 1H) , 3.66 (brS. 2H), 2.50. 2.47. 2.36 (3-S. 9H) .

EXAMPLE C Preparation of 4-(2-chloro-4-nitrophenoχy)-2.3.6- trimethyl-N-trifluoroacetanilide

To a magnetically stirred solution of 4-(2-chloro-4-nitrophenoxy)-2.3.6-trimethylaniline (10.50 grams, 34.23 mmol) prepared in Example B and toluene (50 milliters) was added neat trifluoroacetic anhydride (74.35 grams, 353.9 mmol). The reaction mixture was stirred at room

temperature overnight during which time precipitation of the product occurred. The mixture was filtered on a fritted disc and washed with hexane. This afforded pure 4-(2-chloro-4-nitro- phenoxy)-2.3,6-trime h l-N-trifluoroacetanilide (2.9 grams, 7.2 mmol. 27.6%) as an off-white powder. NMR spectroscopic analysis indicated the following: H'-NMR (CDC1 ) 8.37 (d, J « 2Hz. 1H) , 8.05 (d. d; J > 2. 9 Hz. 1H). 7.71 (br S. 1H), 6.77 (S. 1H) ,

6.70 (S. 1H).

EXAMPLE D Preparation of 4-(4-amino-2-chlorophenoχy)-2.3.6- trimethyl-N-trifluoroacetanilide

Into a 250 milliliter Parr bottle was charged 4-(2-chloro-4-nitro phenoxy)-2.3,6- trimethyl-N-trifluoroacetanilide (2.82 grams. 7.56 mmol) prepared in Example C and ethyl acetate (50 milliliters). The bottle was purged with nitrogen and 5% platinum on carbon (280 milligrams) was added. The reaction mixture was hydrogenated for 45 minutes on a rocking, Parr hydrogenator at 40-50 psi hydrogen and room temperature. The catalyst was removed by filtration through celite and the filtrate was concentrated under reduced pressure to afford pure 4-(4-araino-2-chloro- phenoxy)-2.3,6-trimethyl-N-trifluoroacetanilide (2.32 grams. 6.22 mmol. 82%) as an off-white powder. NMR spectroscopic analysis indicated the following: H'-NMR(CDC1 ) 10.23 (br s. 1H) . 6.40-6.86 (m. 3H) , 6.32 (S. 1H) , 4.41 (br s. 2H) , 2.29 (s. 3H). 2.20 (s. 1H) . 2.10 (S, 1H) .

EXAMPLE E Preparation of 4-(2.4-dichlorophenoχy)-2.3.6- trimethylaniline

Into an ice-chilled, magnetically stirred solution of NaNO (453 milligrams, 6.57 mmol) in concentrated sυlfuric acid (3.2 milliliters) was added dropwise a soluton of 4-(4-amino-2-chloro- phenoxy)-2.3.6-trimethyl-N-trifluoroacetanilide (2.25 grams. 6.036 mmol) prepared in Example D in acetic acid (14.7 milliliters). The reaction temperature was maintained below 15°C. After addition, the reaction mixture was stirred for 2 hours at room temperature. During the latter time period a solution of cuprous chloride was prepared as follows: to a solution of CuSO_ I (HO) _.

4 2 5

(5.26 grams. 21.07 mmol), NaCl (899 milligrams. 15.39 mmol) and water (23.7 milliliters) was added under nitrogen a solution of NaHSO (841.6 milligrams. 8.088 mmol). NaOH (485.2 milligrams, 12.13 mmol) and water (3.96 milliliters). The mixture was stirred and afforded a white precipitate. The supernatent liquid was decanted off and the precipitate was washed Clx) with water. Concentrated HCl (14 milliliters) was added affording a green-black solution. To this solution was added dropwise with stirring the diazonium salt in acetic acid/H SO prepared above and the mixture stirred for 30 min. at room temperature. The reaction mixture was diluted with ethyl acetate, washed (3x) with H ₂ 0. (lx) with brine and dried over sodium sulfate. Concentration under reduced pressure afforded crude 4-(2,4-dichlorophenoxy)- 2,3,6-trimethyl-N-trifluoroacetanilide (2.0 grams)

as an orange oil. To this product was added methanol (20 milliliters) followed by NH NH •

H O (30 milliliters). The reaction mixture was refluxed and stirred for 5.5 hours, allowed to cool, diluted with water and then extracted with toluene.

The organic layer was washed (2x) with saturated

NH.Cl; (lx) with H„0; (lx) with brine and dried 4 2 over sodium sulfate. Concentration under reduced pressure afforded crude 4-(2,4-dichlorophenoxy)- 2.3.6-trimethylaniline (1.49 grams) as an oil. The reaction mixture was purified by flash column chromatography (70:1 loading ratio. 3:1 hexane:ethyl acetate) to afford pure 4-(2.4-dichlorophenoxy)- 2,3.6-trimethylaniline (810 milligrams, 2.73 mmol, 45% yield) as off white crystals having a melting point of 80.5°C - 84°C. NMR spectroscopic analysis indicated the following: H'-NMR (CDC1 ): 7.27 (d. J = 2Hz, 1H). 6.93 (d. d; J = 2, 9Hz. 1H) . 6.57 (s. 1H). 6.42 (d. J = 9HZ. 1H). 3.36 (br s. 2H) . 2.06 (s. 6H). 1-.96 (S. 3H) .

EXAMPLE 1 Preparation of 1-.2.3-Dichloro-4-(2.4-dichloro- phenoxy)-6-methylphenyl1-3-(2.6-difluorobenzoyl) urea

Part A: Preparation of 3-chloro-4-(2.4-dichloro- phenoxy)-6-methylnitrobenzene

Into a one liter three-necked round bottom reaction flask equipped with a magnetic stirrer. reflux condenser, thermometer and nitrogen inlet was charged 36.4 grams (176.7 mmol) of

4.5-dichloro-2-methylnitrobenzene, 35.9 grams (220.2 mmol) of 2.4-dichlorophenol. 21.1 grams (152.5 mmol) of potassium carbonate and 350 milliliters

dimethylforamide. The reaction mixture was stirred and refluxed for a period of 2 hours, filtered while still warm, then cooled to room temperature and concentrated under reduced.pressure. The residue was diluted with methylene chloride and the organic layer was washed with brine, dried over anhydrous

Na„SO_, and concentrated under reduced pressure 2 4 to afford a crude product as a dark brown, viscous liquid. The addition of hexane and toluene afforded a light brown solid which was subjected to flash column chromatography (4:1-2:1 hexane:toluene) to give pure 3-chloro-4-(2,4-dichlorophenoxy)-6-methyl- nitrobenzene (24.5 grams. 73.7 mmol. 42%). NMR spectroscopic analysis indicated the following: H'-NMR (CDC1 ): 8.26 (br S. 1H) . 7.60 (d. J=2Hz. 1H). 7.35 (d.d; 2.9 Hz; 1H) . 7.06 (d. J=9Hz. 1H) . 6.59 (S. 1H). 2.53(S. 3H) .

Part B: Preparation of 3-chloro-4-(2.4-dichloro- phenoxy)-6-methylaniline

Into a 250 milliliter Parr bottle was charged 24.44 grams (73.48 mmol) of 3-chloro- 4-(2.4-dichlorophenoxy)-6-methylnitrobenzene prepared in Part A and 150 milliliters of toluene. The bottle was purged with nitrogen and solid 5% platinum on carbon was added (3.7 grams). The reaction mixture was then hydrogenated for 1 hour at 40-50 psi hydrogen and room temperature on a rocking Parr hydrogenator. The catalyst was removed by filtration through celite and the filtrate was concentrated under reduced pressure to afford the product as a thick yellow oil. The addition of

hexane afforded pure 3-chloro-4-(2,4-dichloro- phenoxy)-6-methylaniline (20.41 grams, 67.5 mmol, 92%) as a light brown solid. NMR spectroscopic analysis indicated the following: H'-NMR (CDC1 ) : 7.41 (d. J=2Hz. IH). 7.10 (d.d; J=2.9 Hz; IH) , 6.78 (s. IH), 6.72 (s, IH). 6.55 (d. J=9Hz. IH) , 3.59 (br s. 2H). 2.10 (s, 3H).

Part C: Preparation of 2.3-dichloro-4-(2.4-dichloro- phenoxy)-6-me hylaniline

Into a 100 milliliter round bottom reaction flask equpped with a magnetic stirrer and nitrogen inlet was charged 9.41 grams (31.10 mmol) of

3-chloro-4-(2,4-dichlorophenoxy)-6-methylaniline prepared in Part B, 62 milliliters of acetic acid and 4.6 grams (34.21 mmol) of N-chlorosuccinimide.

The mixture was stirred at ambient temperature for

45 minutes and diluted with toluene and saturated

Na SO solution. The toluene layer was washed with saturated Na SO solution (3x), water (3x).

5% NaOH solution (3x), water (lx) and brine; dried over Na2.SO4. and concentrated under reduced pressure to afford a crude product as a thick brown oil. Flash column chromatography (100:1 loading ratio; 3:1 hexane:ethyl acetate) afforded 2,3-dichloro-4-(2,4-dichlorophenoxy)-6- methylaniline (1.47 grams, 4.36 mmol. 14%). NMR spectroscopic analysis indicated the following: H'-NMR (CDC1 ₃ ) 7.43 (d. J=2Hz. IH) . 7.30 (d. d; J=2. 9Hz. IH). 6.74 (s, IH) . 6.56 (d. J=9Hz, IH) , 4.08 (br s. 2H). 2.18 (s, 3H) .

4 ?

Part D: Preparation of 1-T2.3-dichloro-4-(2,4- dichloroρhenoχy)-6-methylρhenvn-3-(2,6-difluoro¬ benzoyl) urea

Into a magnetically stirred solution of 2,3-dichloro-4-(2.4-dichlorophenoxy)-6-methyl- aniline (1.43 grams. 4.24 mmol) prepared in Part C in toluene (4 milliliters) and hexane (4 milli¬ liters) under nitrogen atmosphere was added neat 2.6-difluorobenzoyl isocyanate (780 milligrams, 4.24 mmol) and the mixture was stirred overnight at room temperature. The resultant precipitate was collected by filtration, washed with hexane and dried to give pure l-[2,3-dichloro-4-(2,4- dichlorophenoxy)-6-methylphenyl]-3-(2,6- difluorobenzoyl) urea (670 milligrams, 1.29 mmol, 28%) as a white solid having a melting point of 196°C-199°C. Elemental analysis of the white solid indicated the following:

Analysis: C H ,C1.F N 0, 21 12 4 2 2 3

Calculated: C. 48.49; H. 2.33; N, 5.39. Found: C. 48.18; H. 2.43; N. 5.34

EXAMPLES 2 and 3 .In a manner similar to that employed in the preceding examples, and using one of the synthesis schemes previously disclosed, other urea compounds were prepared. The identity of the substituents on the generic formula and the analytical data are set forth in Table I below:

Table I

Representative l-(4-Phenoxypht.'nyl)-3-Bcnzoyl Urea Compounds

Elementa 1 Analysis Melting

Calculated (ound Point

Example Molecular Formula X X ' ^R 3 R R' R" R'" JL_ _____ _____ C H N °C

2 C ₂₎ H ₁ 2Br ₁ Cl ₃ F ₂ N ₂ θ3 F F Cl Cl CH ₃ Br H Cl H 44.67 2.14 4.96 44.66 2.22 4.91 189-190

3 ^C 23 ^H 18 ^C1 2 ^F 2 ^N 2°3 F F Cth CH-, CH ₃ Cl H Cl H 57.63 3.78 5.84 57.89 3.90 5.67 193-195

Certain representative examples of the new compounds were evaluated to determine their pesticidal activity against certain insects, including a caterpillar and a beetle. The new compounds were also tested for phytotoxicity on important economic crops including snap bean, cucumber and sorghum. The new compounds were further evaluated for mammalian toxicity.

Suspensions of the test compounds were prepared by dissolving 100 milligrams of compound in 1.5 milliliters of dimethylforamide and then adding 8.5 milliliters of an acetone solution containing 0.25 percent of an alkylphenoxy polyethoxyethanol surfactant, as an emulsifying or dispersing agent. The resulting solution was mixed into 30 milliliters of water to give roughly 40 milliliters of a suspension containing the compound in finely divided form. The thus-prepared stock suspension contained 2.5 percent by weight of compound. The test concentrations in parts per million by weight employed in the tests described hereinbelow were obtained by appropriate dilutions of the stock suspension with water. Sonication was used where necessary to obtain a homogeneous suspension. The test procedures were as follows:

Southern Armvworm Leaf Spray Test

Larvae of the southern armyworm (Spodoptera eridania. (Cram.)), reared on Tendergreen bean plants at a temperature of 80°+, 5° F. and a relative humidity of 50 + 5 percent, constituted the test insects.

The test compounds were formulated by diluting the stock suspension with water to give a suspension containing the test compound at the concentrations (in parts of the test compound per million parts of final formulation) as set forth in the Tables below. Potted tendergreen bean plants of standard height and age were placed on a revolving turntable and sprayed with 100 milliliters of test compound formulation by use of a DeVilbiss spray gun set at 40 psig air pressure. This application, which lasted 25 seconds, was sufficient to wet plants to run-off. As a control. 100 milliliters of a water-acetone-emulsifier solution containing no test compound were also sprayed on infested plants. When dry. the paired leaves were separated and each one was placed in a 9 centimeter Petri dish lined with moistened filter paper. Five randomly selected larvae were introduced into each dish and the dishes were closed. The closed dishes were labeled, and held at 80° - 85° F. for five days. Although the larvae could easily consume the whole leaf within twenty-four hours, no more food was added. Larvae which were unable to move the length of the body, even upon stimulation by prodding, were considered dead. Percent mortality was recorded for various concentration levels.

Mexican Bean Beetle Leaf Spray Test

Third instar larvae of the Mexican bean beetle (Ephilachna varivestis. Muls.), reared on Tendergreen bean plants at a temperature of 80° +_ 5° F. and 50+5 percent relative humidity, were the test insects.

The test compounds were formulated by diluting the stock suspension with water to give a suspension containing the test compound at the concentrations (in parts of the test compound per million parts of final formulation) as set forth in the Tables below. Potted Tendergreen bean plants of standard height and age were placed on a revolving turntable and sprayed with 100 milliliters of test compound formulation by use of a DeVilbiss spray gun set at 40 psig air pressure. This application, which lasted 25 seconds, was sufficient to wet plants to run-off. As a control, 100 milliliters of a water-acetone-emulsifier solution containing no test compound were also sprayed on infested plants. When dry, the paired leaves were separated and each was placed in a 9 centimeter Petri dish lined with moistened filter paper. Five randomly selected larvae were introduced into each dish, and the dishes were closed. The closed dishes were labeled and held at a temperature of 80°+.5° F., for five days. Although the larvae could easily consume the leaf within 24 to 48 hours, no more food was added. Larvae which were unable to move the length of the body, even upon stimulation, were considered dead.

Tobacco Budworm and Cotton Bollworm Leaf Spray Bait Test

Second instar larvae of the tobacco budworm (weighing about 2.5 mg) (Heliothis virescens, F.) and the cotton bollworm (weighing about 2.5 mg) (Heliothis zea. (Boddie)). obtained commercially and reared on artificial diet at a temperature of 80°+. 5° and a relative humidity of 50+ 5 percent, constituted the test insects.

Using a procedure similar to the above, but substituting cotton plants for snapbeans, treated and dried cotton leaves were introduced into 9 cm Petri dishes which were organized in to groups of 10-dish sets. One randomly selected larvae was introduced into each dish of a ten dish set and the dishes were closed. The closed dishes were labelled and held at 80°+. 5° F. for five days. Larvae which were unable to move the length of the body, even upon stimulation, were considered dead. Percent mortality was recorded for various concentration levels.

The biological properties of certain representative examples of the compounds of this invention are set forth in Tables II, III and IV below.

Table II

Biological Properties of Representative

1-(4-Phenoxyphenyl)-3-Benzoyl Urea Compounds

Compound Prepared Activity at 100 _£P _j nJ3) In Example No. S W^ ¹ ^ MBB ⁽ 2 ⁾

1 A A

2 A* A*

(1) Southern Armyworm

(2) Mexican Bean Beetle

(3) Code: A = 71 - 100% Kill

B = 31 - 70% Kill C = 0 - 30% Kill ^Tested at 25 ppra.

Examples 4 and 5 and Comparative Example A

In order to demonstrate the enhanced biological activity against Mexican Bean Beetle, representative l-(4-phenoxyphenyl)-3-benzoyl urea compounds of this invention were compared with known compounds. The results are set forth in Table III below.

TABLE III

Comparison of Representative 1-(4-Phenox ^' yphenyl.-3-Benzoyl Urea

Compounds with Known Compounds Against Mexican Bean Beetle

Mexican Bean Beetle

Example/ Application Percent Control Comparative Example Compound Structure Rate (ppm) (after 5 days)

^r 0

From the data included in Table III. it is evident that the l-(4-phenoxyphenyl)-3-benzoyl urea compounds of this invention provide enhanced biological activity against the Mexican Bean Beetle in comparison with known compounds. As used in Table III. the compound of Comparative Example A was prepared in a manner similar to the procedure described in Japanese Patent Application 5 6092 857.

Examples 6 and 7 and Comparative Example B

In order to demonstrate the enhanced biological activity against. Heliothis spp.. representative l-(4-phenoxyphenyl)-3-benzoyl urea compounds of this invention were compared with known compounds. The results are set forth in Table IV below.

TABLE IV

Comparison of Representative l-(4-Phenoxyphenyl)-3-Benzoyl Urea

Compounds with Known Compounds Against Heliothis

Heliothis Vlrescens

Example/ Application Percent Control Comparative Example Compound Structure Rate (pp ) (after 5 days)

From the data included in Table IV, it is evident that the l-(4-phenoxyphenyl)-3-benzoyl urea compounds of this invention provide enhanced biological activity against the Heliothis spp. in comparison with known compounds. As used in Table IV, the compound of Comparative Example B was prepared in a manner similar to the procedure described in Japanese Patent Application 5 6092 857.

B 4

Although the invention has been illustrated by the foregoing examples, it is not to be construed as being limited to the materials employed therein; but rather, the invention encompasses the generic area as hereinabove disclosed. Various modifications and embodiments can be made without departing from the spirit and scope thereof.