PHENOXYPHENYD - 3-BENZOYL UREA COMPOUNDS

AND PROCESS FOB PREPARATION

This application is a continuation-in-part of U.S. Patent Application Serial No. 495,331, filed May 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 x*o pesticidal compositions and to a method for their use.

Bac -ground 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-[3-chloro-4-(2.4-dichlorophenoxγ)-2,5- dimethylphenyl]-3-(2.6-difluorobenzoyl) urea. l-[3-chloro-4-(2-bromo-4-chlorophenoxy)-2»5-dimethyl- phenyl]-3-(2,6-difluorobenzoyl) urea. l-[3-chloro-4- (2-bromo-4-chlorophenoxy)-2.5-dimethylphenyl]-3-(2-flu orobenzoyl) 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-ρhenoxyphenyl)-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' represents hydrogen or halogen; ,

X' ' represents fluorine or hydrogen with the proviso that when X' is halogen then X' ' is hydrogen; R . R and R are independently methyl, chlorine or bromine; R represents methyl, chlorine, fluorine or bromine; and R', R ' ' and R' ' ' are independently hydrogen, methyl, chlorine, fluorine or bromine provided that at least one of R ¹ . R' ' and R' ¹ ' is other than hydrogen.

Detailed Description As indicated above, the invention relates to novel l-(4 _^ pheπoxyphenyl)-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 ¹ ' and R' ^• ' are as indicated above.

Particularly preferred benzoyl urea compounds are those of the formulas:

wherein X. X', R . R , R , R and R ¹ ' are 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

Representative l-(4- -Phenoxyphenyl)-3-

Benzoγi Urea Compounds

X X ¹ R R' '

F F Cl Cl

Cl H Cl Cl

F Cl Cl Cl

Cl Cl Cl Cl

Br F Cl Cl

Table A (Continued)

Rep esenta ive l-(4-Phenoxyphenyl )-3-

Benzoyl Urea Compounds

R 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

Cl Cl ^' Br Br cr Br Br Br

Cl F Br Br

F ^' F CH ₃ CH ₃

Cl H CH ₃ CH ₃

H F CH ₃ CH ₃

Cl F CH ₃ CH ₃

Cl Cl CH CH 3 3

F F ^« Br CH ₃

F F CH ₃ Br

F F Cl CH 3

F F CH Cl

F F F Cl

F F F Cl

K F F F

Cl H F F

F F F F

Table A (Continued)

Representative l-( -Phenoχy enyl)-3-

Benzoyl Urea Compounds

X X' R R' '

Cl H Cl F

F F Cl F

H Cl F Br

F F F Br

F F Br F

Table B (Continued)

Representative 1-(4-P enoxyphenyl)-3-

Benzoyl Urea Compounds

F H CH ₃ Cl Cl

F F CH Br Cl 3

Cl F CH ₃ Br Cl

Cl Cl CH Br Cl 3

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 ₃ H CH ₃

Cl H CH ₃ CH ₃ H ₃

Table C

Representative 1- (4- Phenoxyphenyl) -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 H ■ CH. Cl CH,

Table C (Continued)

Representative 1-(4-Phenoxy enyl)-3-

Benzoyl Urea Compounds

F H CH ₃ Cl CH 3

F F CH CH CH 3 3 3

H Cl CH ₃ CH ₃ CH ₃

F H CH CH CH 3 3 3

F F CH ₃ Cl Cl

F F CH ₃ CH ₃ H

Cl H CH ₃ CH ₃ H

F F CH ₃ H CH ₃

Cl H CH ₃ H CH ₃

Table D

Representative l-(4-Phenoχyphenyl)-3-

Benzoyl Urea Compounds

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

Cl 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 CH

Cl H CH ₃ CH CH.

F H CH ₃ CH] CH~

F F CH ₃ Br ^' CH^

Cl H CH Br CH

Table D (Continued)

Rep esentative 1-(4-Phenoxy henyl)-3-

Benzoyl Urea Compounds

F F Br Br Br

Cl H Br Br Br

H Cl CH ₃ Cl Cl

F F CH Cl Cl 3

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 H ₃ H

Ta ble E

Rep esentative 1-(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 Br H

F F CH ₃ CH ₃ H

Cl H CH ₃ CH H

Cl F Cl H Cl

F F Cl H Cl

Cl H Cl H Cl

Cl H CH ₃ H CH ₃

F F CH ₃ H CH ₃

H F CH H CH ₃ 3

F F Cl Cl Cl

H F Cl Cl Cl

Table E (Coritinued)

Representative 1-(4-Phenoxyphenyl)-3-

Benzoyl Urea Compounds

R' ' 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 CH CH 3 3 3

F H CH ₃ Cl CH ₃

Cl H CH ₃ Cl CH ₃

F F CH Cl CH 3 3

Tab!.e F -

Representative l-(4l-Phenoxyphenyl ) -3-

Benzoyl Urea Compounds

X X' X' ' ^H ι ^R 2 ^R 3

Cl H 4-F CH Cl CH 3 3 ₃

F H H CH ₃ CH ₃ Cl

Cl F H CH ₃ CH ₃ , Cl

F F H CH ₃ CH ₃ CH ₃

Cl H H CH CH CH 3 3 3

Cl H 4-F CH CH CH 3 3 3

Cl H 5-F CH CH CH 3 3 3

Cl H H Cl Cl Cl

F F H Cl Cl Cl

Cl H 4-F Cl Cl Cl

Cl H 5-F Cl Cl Cl

Cl F H Cl Cl Cl

F F H l CH. Cl

Table F (Continued)

Representative 1-(4-Phenoxyphenyl)-3-

Benzoyl Urea Compounds

X X' X' '

»1 ^E 2 ^E 3

F H H Cl CH ₃ Cl

Cl F H Cl CH ₃ Cl

Cl H 4-F Cl CH ₃ Cl

Cl H 5-F Cl H ₃ Cl

Ta b le G

Representative 1-(4-Phenoxyphenyl)-3-

Benzoyl Urea Compounds

^B 2 R

^R 3

F H CH. Br CH ₃ Cl

Cl H CH; Br H ₃ Cl

Cl H Br Br Br Cl

F F Br _, .Br Br Br

Cl H Br Br Br Br

F F Br CH ₃ CH Cl

H Cl Br CH ₃ CH ₃ Cl

H Cl Br CH ₃ H ₃ Br

F F Br CH ₃ CH ₃ Br

F F Br Cl Cl Cl

H Cl Br Cl Cl Cl

F F Br Cl Cl Br

H Cl Br Cl Cl Br

Cl H Br CH ₃ Br Cl

F F Br CH ₃ Br Cl

Cl H Br CH ₃ Br Br

Br Br Br CH. Br Br

. •ι) f . - . θ - 'fl . . . . 'fl θ '») . . n ^, >) - fj

n

n n o o o o o o o o n o n n n o n o o n n n

H H 0J. 0J. OJ. H H H OJjι ^; OJ. OJ!iiOJa:OJ. OJ.

o o o o o o o o o o o o o o o o o o n o o o

_{. .} H H H 3! _ _. . H H H H H H H H H H H !i; !l! OJ OJ OJ OJ OJ OJ OJ

to to to to to td to O ti ti rt rt rt rt ti c tio n H nH oH Ho Ho Ho inE o _. ior an aoi oa Ho

OJ Oϋ J OJ OJ J

to to o n o n n n w to to n o o ω to t o n n ω w rt rt rt n ri H-' i-' i-' rt rt rt !-■ »-» H-» M rt

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:

organi solvent>

Scheme I

wherein X. X'. X' ¹ . R .. R , R . R. R'. R ¹ ' and R ¹ ' 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 benzaraide 5. according to Scheme II as follows:

organic solvent

- 24, -

Scheme I I

wherein X. X'. X*'. R . R . R . R. R'. R'' and R'*' 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 7. according to Scheme III as ollows:

organic solvent

'

Scheme I I I

wherein X. X'. X''. R . R . R . R. R'. R ¹ ' and R' ' ' 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 ^β 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. Org. Chem. 27. 3742 (1962) as follows:

Scheme IV

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

The substituted phenoxyanilines 2. for which R ₁ is 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 (1) with the proviso that R is not chlorine or bromine. The reaction of a substituted phenol 9. with a chloronitrobenzene 8. to give the nitro ether .10, 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, dimethylformamide. 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 ljD 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 Chero. Rev.. Vol. 65, pp. 51-68 (1965).

Isocyanate 4. can be obtained by reacting the substituted aniline 2. with phosgene. Urea l_ 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' ' ' have the meaning given in Formula (1).

The substituted phenoxyanilines 2. for which R ₁ is chlorine or bromine are obtained upon halogenation of 3,5-disubεtituted-4-phenoxyaniline 11 as depicted in Scheme VII below as follows:

N-halosuccinimide solvent

11

Scheme VII

wherein R is chlorine or bromine and R , R , R. R'. R' ' and R' ¹ ' have the meaning given in Formula (1). Suitable solvents for this transformation include haloalkanes; aromatic hydrocarbons, such as benzene; or polar protic solvents, such as acetic acid. Halogenation of aniline 1.1 may be'effected by its exposure to

chlorine or bromine in a suitable solvent at low temperature or preferably treatment with a N- halosuccinimide in benzene. Temperatures required for the reaction vary according to the identity of substituents R and R but generally fall in the range of 25 ^β C- 80 ^β C.

Phenoxyanilines of type ] are prepared by the method depicted in Scheme V above making use of the 3,4,5-trisubstituted nitrobenzene JL2. as the ■electrophilic component in this coupling reaction. Chloronitrobenzenes of type 12. are illustrated as follows:

12 wherein R and have the meaning given in Formula (1). Chloronitrobenzenes of type 12. are obtained from the corresponding nitroanilines via the Sandmeyer procedure as practiced by Miller et. al. J. Med. Chem. 23. 1083 (1980).

Alternatively, chloronitrobenzenes of type 8. can be prepared through the nitration of a chlorobenzene as typlified by the synthesis of 3,4-dichloro-2.5-dimethylnitrobenzene Ij6 illustrated in Scheme VIII as follows:

13 14 15

HNO.

N

CH-

ϋ

Scheme VIII

The preparation of phenols of type 9. is illustrated by the elaboration of

4-bromo-2-fluorophenol from 2-fluorophenol using the procedure set forth by Mitchell el al.. J.. Org. Chem.. 25. 4733 (1979). Another phenolic intermediate, 2-bromo-4-chlorophenol, is obtained analogously from 4-chlorophenol.

An alternate route to phenoxyanilines of type 2_. in particular the phenoxyaniline 2_1, is depicted in Scheme IX below as follows:

18 17

19

0

20

21

Scheme IX wherein R . R . R . R and R" have the meaning given .in Formula (1) and R ¹¹ is chlorine or bromine. This reaction involves the coupling of an aminophenol 17. with a 4-chloronitrobenzene 1. in the presence of a base to afford 4-nitrophenoxyaniline 19 as described in Schramm et al., Ann.. 740. 169 (1970). Reaction of the amino group in 19. with cyclohexane -1. 2-dicarboxylic anhydride affords i ide 20. Nitro group reduction. Sandmeyer halogenation and deprotection of the amino function afford aniline 2JL. The details of these transformations are given in the experimental section hereinbelow.

Aminophenols of type _1_ are readily available and may be prepared as illustrated in the elaboration of aminophenol 2%. via nitration of a 2. 5-disubstituted phenol 2_2 followed by halogenation and nitro group reduction as depicted in Scheme X below as follows:

- 32 -

Halogenation

24

Reduction

25

Scheme X wherein R ₁ and R have the meaning given in Formula (1) and Y is bromine or chlorine. Their approach to intermediates 22 and 2J. reflect that described by Albert and Sears. _____ Am. Chem. _S oc. , 76.. 4979 (1954).

An alternate and complimentary approach to aminophenols r7 is detailed in Scheme XI as follows:

Θ

^{^} 3

OH

26

Reduction

27

17

Scheme XI wherein R . and R have the meaning given in Formula (1). This involves the reaction of a trisubstituted phenol 2_6 with a diazonium salt prepared from sulfanilic acid to afford the intermediate diazo compound 27. which is reduced to give aminophenol T.. The synthetic methodology used in this approach to aminophenol 11. is that described by Payne and eiden 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 forma ide 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

Q-

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. diatoraaceous 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 caused 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 TMS.

EXAMPLE A Preparation of 4-(2.4-difluorophenoxy)-2,3,5-tri- chloroaniline

Into a 300 milliliter round bottom reaction flask was charged 14.9 grams (51.4 mmol) of 3.5-dichloro-4-(2,4-difluorophenoxy) aniline. 7.2 grams (53.9 mmol) of N-chlorosuccinimide (NCS). and 100 milliliters of benzene. The reaction mixture was refluxed for 2 hours after which time additional

NCS (350 milligrams. 2.6 mmol) was added. Reflux was then continued for an additional 1 hour. The mixture was allowed to. cool, diluted with ethyl acetate (200 milliliters) . washed with H O. saturated NaHCO, and brine; dried over Na SO.

3 2 4 and concentrated under reduced pressure. The oily product obtained was purified by flash column chro atography (1:1 hexane toluene) to afford 4-(2.4-difluorophenoxy)-2, 3.5-trichloroaniline (9.8 grams. 30.2 mmol, 59*) as a dark brown oil. The structure of this material was verified by its H'-NMR spectrum (CDC1 ) 7.30-6.10 ( . 3H) . 6.75 (s. 1H). 4.18(br s. 2H).

EXAMPLE B

Preparation of 2-chloro-4-(2,4-dichlorophenoxy)-

3.5-dimethylaniline

Into a 200 milliliter three-necked, round bottom reaction flask was charged 6.76 grams (24.0 mmol) of 4-(2,4-dichlorophenoxy)-3, 5-dimethyl aniline .and 48 milliliters of benzene.

N-chlorosuccinimide (3.85 grams, 28.8 mmol) was then added and the resultant heterogeneous mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate. washed (2x) with saturated Na SO solution and dried over Na SO . Concentration under reduced 2 4 pressure afforded the crude product as a dark oil.

This material was filtered through a short column of silica gel using 9:1 hexane: ethyl acetate as an eluant. Solvent removal under reduced pressure afforded

2-chloro-4-(2.4-dichlo ophenoxy)-3, 5- ime hy1- aniline (6.5 grams) contaminated with at least three

other products. This material was placed in a Parr bottle and dissolved in toluene (50 milliliters). The Parr bottle was purged with nitrogen. 5\ platinum on carbon (650 milligrams) was added and the mixture was hydrogenated for 1 hour at 40-50 psi and room temperature on a rocking Parr hydrogenator. Filtration through a pad of celite.solvent removal and flash chromatography (9:1 hexane: ethyl acetate afforded pure 2-chloro-4-(2.4-dichlorophenoxy)-

3.5-dimethyl aniline (3.1 grams, 9.8 mmol. 41*) as a crystalized solid having a melting point of 89°C-93 ^β C. Elemental analysis of the crystalline solid indicated the following:

Analysis: ^c ₁₄ ^H ₁₂ ^cl ₃ ^NO

Calculated: C.53.11; H. 3.82; N. 4.42.

Found: C. 53.38; H. 3.98 N. 4:30.

^* EXAMPLE C Preparation of 2.5-dichloro-4-(2,4-dichlorophenoxy)- 3-methylaniline and 2, 3-dichloro-4-(2, -dichloro- phenoxy)-5-methylaniIine

Into a magnetically stirred solution of 3-chloro-4-(2,4-dichlorophenoxy)-5-methylaniline (9.0 grams. 29.7 mmol) in benzene (60 milliliters) was added solid N-chlorosuccinimide (4.4 grams, 32.7 mmol). The mixture was stirred at room temperature for 1.5 hours, transferred to a separatory funnel and washed with saturated Na SO solution (3x), water (2x) and brine (lx). The organic layer was dried over Na SO and concentrated under reduced pressure to afford the crude product (10.08 grams) as a dark brown oil. Flash column chromatography on 500 grams of silica gel (3:1 hexane:ethyl acetate)

afforded pure 2.5-dichloro-4-(2.4-di«chlorophenoxy)-

3-methylaniline (2.85 grams, 7.4 mmol. 25*) having a melting point of 96°C-97°C and 2,3-dichloro-4- (2, -dichlorophenoxy)-5 methylaniline (2.16 grams. 6.4 mmol. 22*) having a melting point of 95 ^β C. Recrystallization from methanol afforded analytical samples. Elemental analysis of the samples indicated the following:

Analysis: C H Cl NO

Calculated: C. 46.32; H. 2.69; N, 4.15.

Found (2.5-dichloro-): C. 46.30; H. 2.54; N. 4.16.

Found (2.3-dichloro-) : C, 46.18; H, 2.72; N. 4.02.

EXAMPLE D

Preparation of 2-bromo-4-(2-bromo-4-chlorophenoxy)-

3,5-dichloroaniline

Into a magnetically stirred solution of

4-(2-bromo-4-chlo ophehoxy)-3,5-dichloroaniline

(6.38 grams. 17.36 mmol) in benzene (35 milliliters) was added N-bromosuccinimide (3.71 grams. 20.83 mmol). The reaction mixture was stirred for two hours at room temperature, transferred to a separatory funnel and washed with saturated

Na SO solution (2x). water (2x) and brine

(lx). The organic layer was dried over Na SO

2 4 and concentrated under reduced pressure to afford the crude product which when subjected to flash column chromatography on 760 grams of silica gel (4:1 hexane:ethyl acetate) afforded pure 2-bromo-4-(2-bromo-4-chlorophenoxy)-3.5- . dichloroaniline (5.15 grams. 11.53 mmol. 66*).

Elemental analysis of the product indicated the following:

Analysis: C H Br Cl NO

Calcaluted: C. 32.28; H. 1.35; N. 3:13.

Found: C. 32.48; H. 1.24; N. 2.92.

EXAMPLE E Preparation of 4-amino-2,3,6-trimethylphenol

Into a solution of sulfanilic acid (13.0 grams, 68 mmol) in water (68 milliliters) contained in a 250 milliliter round bottom flask equipped with a magnetic stirrer. internal thermometer and ice bath at 15 ^β C was added solid Na CO (3.69 grams, 34 mmol) followed by a solution of NaNO (5.1 grams. 74 mmol) in water (14 milliliters). The latter addition caused a color change from milky-white to orange. A separate 500 milliliter three-necked flask equipped with a magnetic stirrer, internal thermometer and ice bath was charged with concentrated hydrochloric acid (12 milliliters),, ice (68 grams) and the solution of the diazonium salt prepared above. This mixture was stirred at 15°C for 45 minutes. Meanwhile a third flask (1 L) equipped with an internal thermometer, nitrogen inlet, condenser, addition funnel and mechanical stirrer was charged with water (68 milliliters). NaOH (14.96 grams, 318 mmol) and 2. 3, 6-trimethylphenol (9.30 grams, 68 mmol). This mixture was cooled to .0°C by means of an ice-salt mixture and the diazonium salt - hydrochloric acid mixture prepared above was added dropwise while maintaining the temperature below 5°C. Upon completion of the diazonium salt addition the

reaction mixture was warmed to 52°C and solid Na.S.O. (3.13 grams, 18 mmol) was added. Stirring was continued and the mixture heated to 80 ^β C whereupon additional Na 2_S2_04. (28.2 grams.

162 mmol) was added in three equal portions (9.4 grams each) at 5 minute intervals. The mixture was heated at 80 ^β C under nitrogen for 20 minutes-, cooled to room temperature and filtered to afford the crude product as a yellow solid. The solid was dissolved in ethyl acetate (300 milliliters) and washed with water. The organic layer was dried over Na SO and concentrated under reduced pressure to afford 4-amino-2,3,6-trimethylphenol in quantitative yield which was used successfully in subsequent reactions without further purification. H'-NMR (CDC1 ) 6.30 (S, 1H) . 2.11 (S. 9 H) .

EXAMPLE 1 Preparation of 1-[3-Chloro-4-(2. -dichlorophenσ_y)- 2,5-dimethylphenyl1-3-(2,6-difluoroben oyl)u, ea

Part A: Preparation of 3-chloro-4-(2.4-dichloro- phenoxy)-2,5-dimethylnitrobenzene

Into a 250 milliter three-necked round bottom reaction flask equipped with a magnetic stirrer and nitrogen inlet was charged 10.0 grams (45.44 mmol) of 3.4-dichloro-2,5-dimethyl- nitrobenzene. 7.95 grams (48.81 mmol) of 2.4-dichlorophenol. 9.41 grams (68.11 mmol) of potassium carbonate and 60 milliliters dimethylformamide. The reaction mixture was stirred and heated at a temperature of lOO^C for a period of 20 hours and then cooled to room te perature.

filtered and concentrated under reduced pressure.

The residue was diluted with methylene chloride and the organic layer was washed with 4* NaOH solution

(2x) and brine, dried through and concentrated under reduced pressure to afford the crude product as a dark brown, viscous liquid. The addition of hexane and ethyl acetate afforded a light brown solid which was subjected to Kugelrohr distillation (about 180 ^β C and about 0.1 mm mercury) to give pure 3-chloro-4-(2.4- dichlorophenoxy)-2.5-dimethylnitrobenzene (7.17 grams. 20.7 mmol, 45*) as a yellow solid having a melting point of 118°C-121°C. NMR spectroscopic analysis indicated the following: H'-NMR (CDC1 ) 7.76(br S. IH). 7.53 (d. J=2Hz. IH) , 7.12 (d.d; 2,9 Hz; IH). 6.34 (d. J-9HZ..1H). 2.45 (S, 3H) . 2.24(S. 3H).

Part B: Preparation of 3-chloro-4- ( 2 , -dichloro- *• phenoxy)-2,5-dimethylaniline _r

Into a 250 milliliter Parr bottle was charged 6.59 grams (19.01 mmol) of 3-chloro-

4-(2.4-dichlorophenoxy)-2.5-dimethylnitrobenzene prepared in Part A and 15 milliliters of toluene.

The bottle was purged with nitrogen and solid 10* platinum on carbon (650- milligrams) was added. The reaction mixture was then hydrogenated for 45 minutes at 43-47 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)-2,5-dimethylaniline (4.82 grams, 15.22 mmol. 80*) as a white powder. NMR spectroscopic analysis indicated the following: H'-NMR (CDC1 ) 7.36(d. J=2H. IH). 6.95 (d.d; J _* 2.9 Hz; IH) . 6.40 (br s, IH). 6.32 (d. J-9Hz. IH). 3.54 (br s. 2H). 2.15 (s. 3H), 2.02 (s, 3H) .

Part C: Preparation of l-r3-chloro-4-(2,4-dichloro- phenoxy)-2.5-dimethylphenyn-3-(2.6-difluorobenzoyl) urea

Into a magnetically stirred solution of

3-chloro-4-(2.4 dichlorophenoxy)-2.5-dimeth laniline

(1.5 grams. 4.73 mmol) prepared in Part B in toluene

(15 milliliters) under nitrogen atmosphere was added neat 2.6-difluorobenzoyl isocyanate (1.3 grams. 7.10 mmol) and the mixture was refluxed for a period of 1 hour. The reaction mixture was allowed to cool and hexane (3 milliliters) was added to induce crystallization. The resultant precipitate was filtered and washed successively with hexane and toluene to give pure l-[3-chloro-4-(2.4- dichlorophenoxy)-2.5-dimeth lphen 13-3-(2.6- difluorobenzoyl) urea (2.29 grams, 4.58 mmol, 97*) as a white solid having a melting point of

188°C-190°C. Elemental analysis of the white solid indicated the following:

Analy ¹ sis: C2_,2_H,15_C13 _. F„2N2„0.3,

Calculated: C. 52.87; H. 3.03; N. 5.61. Found: C- 52.91; H. 3.07; N. 5.65

EXAMPLE 2 Preparation of l-r3-Broao-4-(2.4-dichlorophenoxy)- 2.5-dimethylphenyπ-3-(2.6-difluorobenzoyl)urea v

Part A: Preparation of 2-bromo-3.6-dimethyl-4- nitrophenol

Into a magnetically stirred suspension of 2.5-dimethyl-4-nitrophenol (12.70 grams, 75.98 mmol) in CH Cl (150 milliliters) at room temperature was added portionwise N-bromosuccinimide (14.88 grams. 83.58 mmol). The mixture rapidly became homogeneous and after one hour thin layer chromatography (3:1 hexane:ethyl acetate) indicated complete consumption of the starting material and formation of a single major product. Saturated Na SO solution (15 milliliters) was added and the solvent was removed under reduced pressure. Ethyl acetate was then added and the organic layer was washed with water and brine, dried over <- Na SO and concentrated under reduced.pressure to afford 2-bromo-3.6-dimethyl-4- nitrophenol (13.6 grams, 55.3 mmol, 73*) as a rust colored solid. H'-NMR (CDC1 ) 9.26 (brS, IH) , 7.71 (S, IH). 2.60 (S. 3H) . 2.31 (S. 3H) .

Part B: Preparation of 4-amino-2-bromo-3 , 6- dimethylphenol

Into a Parr bottle was charged 2-bromo-3, 6-dimethyl-4-nitrophenol (13.6 grams, 55.3 mmol) prepared in Part A and ethyl acetate (50 milliliters). The reaction vessel was purged with nitrogen and 5* platinum on carbon (1.36 grams) was added immediately following the purge.

Hydrogenation was carried out on a rocking Parr hydrogenator for 1.5 hours at 40-50 psi hydrogen and room temperature. The reaction mixture was filtered through celite and concentrated under reduced pressure to give 4-amino-2-bromo-3,6- di ethylphenol as a brown solid in quantitative yield. H'-NMR (CDC1 -DMSO-d ). 6.40 (S. IH) , 2.17 (brS. 6H).

Part C: Preparation of 3-bromo-4-(2-chloro-4- nitrophenoxy)-2,5-dimethyIaniline

Into a dry 250 milliliter round bottom flask equipped with a magnetic stirrer and nitrogen inlet was added 4-amino-2-bromo-3.6-dimethylphenol (11.94 grams. 55.3 mmol) prepared in Part B and dry dimethylsulfoxide (118 milliliters). Potassium t-butoxide (7.26 grams. 64.65 mmol) was added portionwise under nitrogen and the mixture was stirred at room temperature for 0.5 hours. Solid 3,4-dichloronitrobenzene (13.33 grams, 70.52 mmol) was then added and the reaction mixture was heated at 50°C for 48 hours. After cooling the mixture was diluted with toluene and washed successively with saturated NH„C1 solution (3x) and with 5* NaOH solution until the aqueous washes remained colorless. This was followed by washes with water and brine, drying over Na 2_SO4. and solvent removal under reduced pressure to afford the crude product (9.4 grams) as a dark red-brown oil.. Flash column chromatography on 650 grams of silica gel (3:1 hexane:ethyl acetate) afforded pure 3-bromo-4-(2-chloro-4-nitrophenoxy)-2.5- dimethylaniline (4.7 grams. 12.6 mmol. 23*) as a

yellow-brown solid. H'-NMR (CDC1 ) 8.42 (d. J » 2Hz. IH). 8.01 (d.d; J - 2. 9 Hz; IH) . 6.55 (d. J =* 9 Hz. IH). 6.58 (S. IH) . 3.73 (brS. 2H) . 2.28 (S. 3H). 2.06 (S. 3H).

Part D: Preparation of 8-f3-bromo-4-(2-chloro-4- nitrophenoxy) -2 , 5-dimethylphenyπ-8-azabicyclo f 4. 3 .01 nonan-7 , 9-dione

To a solution of 3-bromo-4-(2-chloro-4- nitroρhenoxy)-2.5-dimethylaniline (4.7 gra'ms. 12.65 mmol) prepared in Part C in toluene (40 milliliters) was added cis-1,2-cyclohexane dicarboxylic anhydride

(20.48 grams. 132.83 mmol) and a spatula tipful of toluene sulfonic acid. The reaction mixture was heated at reflux overnight and allowed to cool; washed with 5* NaOH solution (5x). water (3x) and brine (lx); dried over Na„SO. and concentrated

2 4 under reduced pressure to afford the crude desired product as a thick brown oil (5.43 grams. 10.69 mmol. 84*) which crystallized on standing and had a melting point of 187 ^β C-190°C. H'-NMR (CDC1 ) ..40 (d. J - 2Hz. IH). 8.02 (d.d; J - 2. 9 Hz. IH) . 7.00(br. 5, IH). 6.55 (d. J = 9Hz. IH) . 3.10 (M. 2H). 2.21 (brS. 6H). 1.93 (M. 4H) , 1.58 ( . 4H) .

Part E: Preparation of 8-r4-(4-amino-2- chlorophenoxy)-3-bromo-2.5-dimethylphenyl1-8- azabicyclo T .3.QI-nonan-7,9-dione

Into a Parr bottle was charged 8-[3-bromo- 4-(2-chloro-4-nitrophenoxy)-2,5-dimethylphenyl]-8- azabicyclo[4.3.0] nonan-7.9-dione (3.45 grams, 6.79 mmol) prepared in Part D and ethyl acetate (100 milliliters). The reaction mixture was purged with nitrogen. 5* platinum on carbon (480 milligrams) was

added and the mixture was hydrogenated for 1.5 hours at 40-50 psi hydrogen and room temperature on a rocking Parr hydrogenator. Filtration through celite and concentration under reduced pressure afforded the desired product (2.73 grams, 5.71 mmol. 84*). H'-NMR (CDC1 ) 6.93 (br s. IH) . 6.80 (d. J-2HZ. IH). 6.33 ( . 2H) . 3.45 (br s. 2H) . 3.06 (br m, 2H) 2.4-1.2 ( . 14H) .

Part F: Preparation of 3-bromo-4-(2.4-dichloro- phenoχy)-2.5-dimethyl aniline

Into an ice-chilled, magnetically stirred solution of NaNO (420 milligrams, 6.07 mmol) in concentrated sulfuric acid (3.0 milliliters) was added dropwise a solution of 8-[4-(4-amino-2-chloro- phenoxy)-3-bromo-2.5-dimethylphenyl]-8-azab-icyclo [4.3.0] nonan-7.9-dione (2.66 grams, 5.57 mmol) prepared in Part E i acetic acid (14 milliliters) keeping the internal temperature below 15 ^β C. The reaction mixture was stirred for 15 minutes at 15 ^β C and then for 2 hours at ambient temperature. During this latter time period a solution of cuprous chloride was prepared as follows: to a solution prepared from CuSO *(H O) (4.85 grams. 19.44 mmol). NaCl (830 milligrams, 14.20 mmol) and water (22 milliliters) was added under nitrogen a solution prepared from NaHSO (780 milligrams. 7.46 mmol), NaOH (450 milligrams. 9.56 mmol) and water (4 milliliters). The mixture was swirled and the supernatant liquid was decanted off. The cream colored precipitate was washed with water (3x) until the decanted supernatant liquid was colorless. Concentrated hydrochloric acid (12 milliliters) was

then added affording a pale green solution containing cuprous chloride. To this solution was added dropwise the diazonium salt in acetic and the mixture was stirred for 0.5 hours. The reaction mixture was diluted with ethyl acetate and washed with saturated Na SO solution, water and brine; dried over Na SO, and

2 4 concentrated under reduced pressure to afford crude product (2.4 grams. 4.8 mmol. 86*) as a gold solid.

The crude product (2.0 grams, 4.02 mmol) was dissolved in methanol (8 milliliters) and hydrazine monohydrate (20.1 grams. 402 mmol) was added dropwise. The mixture was heated at reflux for 48 hours, cooled and diluted with ethyl acetate and water. Aqueous hydrochloric acid (2*) was added until the aqueous phase became homogeneous. The organic layer was then washed with water (3x) and brine, dried over Na and concentrated under reduced pressure to afford the desired product (1.10 grams, ^' 3.05 mmol. 76*) as an orange oil which slowly crystallized on standing. H'-NMR (CDC1 ) 7.45 (d. J - 2HZ. IH) . 7.05 (d. d: J « 2. 9 Hz; IH). 6.54 (brS. IH) . 6.37 (d. J » 9 Hz. IH) . 3.63 (brS. 2H) . 2.26 (S. 3H). 2.06 (S. 3H) .

Part G: Preparation of 1-(3-bromo-4-(2. - dichlorophenoxy)-2,5-dimethylphenyl)-3-(2.6- difluorobenzoyl)urea

Into a magnetically stirred solution of 3-bromo-4-(2-4-dichlo ophenoxy)-2.5-dimethylaniline (960 milligrams. 2.67 mmol) prepared in Part F in 1:1 hexane:toluene (5 milliliters) was added neat

2, 6-difluorobenzoyl isocyanate (490 milligrams, 2.67 mmol) and the mixture was stirred under a nitrogen atmosphere for 10 minutes. The resultant precipitate was collected on a filtered funnel, washed with toluene and dried to afford the desired product (1.26 grams. 2.3 mmol. 87*) as an off-white powder having a meting point of 205 ^β C-209 ^β C. NMR spectroscopic analysis indicated the following: H'-NMR (CDC1 ) 11.60 (br S. IH) . 10.17 (br s. IH). 8.00-7.10 (m. 6H) . 6.43 (d. J - 9Hz. IH). 2.39 (s. 3H). 2.11 (s. 3H) .-

EXAMPLES 3 - 102 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:

ji e Rfprfientatlve l-( 4-P yno»yp envn-3-8tnroyl Urea Compound!

Ca lM« ..•* r IQΓ_U|< £ I' _! βι B2 83 - fi' B B

3 ^C 20 ^H 9 ^C, S f ₂ N ₂ 03 ( H Cl Cl Cl c 1 H C 1 H 44.43

4 ^C 23 ^H I8 ^CI 2»Λ - ( H " " CH3 c 1 H C 1 H $7.64

5 C ₂₁ H,2C) 4»2><2°3 f H Cl Cl CH3 c 1 H C 1 H 48.49 b C ₂₁ H _|2 C1 ₄ »2N ₂ 0 _j ( H Cl t«3 Cl c 1 H C 1 H 41.49

1 C22H _1S C1 J'J - - f H Cl C"3 CH _j C I ' M C 1 H 52.87 β C ₂₀ H _I0 C1 b"2°3 Cl H II Cl Cl Cl c 1 H C 1 H 44.57

9 C ₂ 2H _H CI 4«2θ Cl H H Cl CHj CH3 c 1 H C 1 H 53.04

10 C ₂₂ H ₁₍ ,CI 4*2°3 . Cl H H CH ₃ Cl CH3 c 1 H C 1 H 53.04

1) C20> -jCl _b f,N ₂ 0 ₃ Cl F H Cl Cl cι c 1 H C 1 H 43.13

12 C22"|5 I 4' ^| N2<>3 Cl f H C" Cl CH3 c 1 H C 1 H 51.19

13 ^c 22»liC» S ^N -°3 Cl Cl H CH _j Cl CHj C 1 H C 1 H 49.61

14 C ₂ 2H, ₆ C) 3' ^| N2«>3 1 H H Cl C" CHJ C 1 H C 1 H 54.85

IS C ₂ 2H, ₆ Cl 3> l 3 f H H CH _j Cl CH3 C 1 H C 1 U 54.85 lb C ₂₂ H, ₅ CI 4'l«2°3 Cl H i f CH ₃ Cl CH _j C 1 H C 1 H 51.19

17

IB

blf I (Continued)

, eprctenUtlvt l l--((44--PPhh ..nnoo««vypphhttnnvvinl--33--8Benntooy| Una Compound*

flt_tntιl Λnalvi It Melting

Cilςg ittd Found Point

I* .wit M olfculir rornwli ϊ' Bl -2 8j B B'. B ' B' JL JL JL ___ JL N ^• c

19 ^c 20 ^H 9 ^Br 2 ^c, 3 ^f 2»*2 ⁰ 3 f H Br Cl Cl Br H C 1 H 38.16 1.44 4.45 38.38 1.38 4.37 204-207

20 ^c 22 ^M 15 ^Br l ^c, 2 ^f 2 ^H 2°3 F H Cl CH ₃ CH _j Br H C 1 H 48.56 2.78 5.15 41.55 2.82 5.08 215 217

21 ^c 22 ^H 15 ^B n ^c '2 ^f 2 ^N 2 ⁰ 3 F H CHj CHJ Br H C 1 H 48.56 2.71 $.15 49.49 2.99 5.30 190.5-1

22 C2θH)θBr _l l _i N ₂ O Cl H H Cl l Br H C 1 H 41.17 1.73 4.80 40.63 1.57 4.85 199-200

23 C2 ₀ H ₁₀ Br2Cl M ₂ θ3 Cl H H Br Cl Cl H C 1 H 38.26 1.61 4.46 38.26 1.59 4.37 205.5-2

24 C ₂₂ H _U Br,Cl3N2θ ₃ Cl H H CHj CHj Br H C 1 M 48.70 2.17 $.16 49.20 3.08 6.16 190-190

25 C2 ₀ H, ₀ BrιCl4f ₁ N2θ3 H H Cl l Br H C 1 H 42.37 1.78 4.94 42.52 1.91 4.82 183.5-1

2b ^c 20 ^H 10 ^Br 2 ^c '3 ^f l ^N 2 ⁰ 3 H H Ir Cl Br H C 1 H 39.29 1.6$ 4. $8 39.32 1.93 4.46 192-195

27 C22H ^β r,Cl ₂ F,H2θ3 H H Cl ™3 CH _j Br H C 1 H 50.22 3.06 $.32 $0.02 3.08 5.25 161.5-1

28 C ₂₂ Hι _fc ^β r,Cl ₂ f,N2θj H H CH ₃ CHj Br M C 1 H 50.22 3.06 $.32 50.16 3.14 5.30 168.5-1

29 C ₂₂ H, _s Br,Cl3F,N2θj Cl F H CHj CHJ Br H C 1 H 47.13 2.11 4.99 47.92 2.84 4.85 230-231

30 C ₂₂ H, ₅ flr ₂ CI,F ₂ N ₂ Oj F H CH ₃ CH ₃ Br H 6 r H 44.88 2.57 4.76 44.89 2.62 4.64 19b-\97

31 ^c 22 ^H 16»f 2 1 ₂ M ₂ 0 ₃ Cl H H CH _j CH ₃ Br H 8 r H 45.00 2.15 4.7) 4$.26 2.74 4.70 194-197

32 C ₂₂ H ₁₆ βr ₂ Cl,r,N ₂ 0j H H CHJ CH ₃ Br H B r H 46.32 2.83 4.91 46.26 2.69 4.89 191-194

33 ₂₂ H, ₅ ^β r ₂ l2 ,« ₂ θ3 Cl F H CHJ CH _j Br H 8 r H 43.67 2.50 4.63 44.08 2.56 4.55 215-218

34 C ₂₀ H ₉ C1 ₃ F4N ₂ 0 ₃ F H Cl Cl F H F H 47.32 1.71 5.52 47.11 1.84 5.36 211-213

35 C ₂₂ H _ls Cl,f4M ₂ 0 ₃ F H CH _j CH _j F H F H 56.60 3.24 6.00 56.77 3.25 6.04 163-154

3b C ₂₀ H ₁₀ Cl f2N ₂ 03 Cl H H C) Cl f H f H 47.47 1.99 5.64 47.46 2.01 5.45 180- 183

-

-. _* . _* «

H ι— « <■ mt m o «< -> <• «n o «•

OmmiO X — X — X X — X — X

rt* - *— rt* *~

1+ule I (Continued) Rep es tativ l-(4-Pheno-yphenyl)-3-Benroyl Ure« Compound

fxample o Itculjr formulj A A'

73 C2 )H| ₉ CljH ₂ 0 l H H CH ₃ CHJ Cl H CHJ H $7.82 8 4.11 5.72 192.5-193

74 c ₂ lH _la Cl4N ₂ 0 _j Cl Cl H CH _j C"3 Cl H CHJ H $3.93 3.51 6.50 216-217.6

75 c ₂ ,H, _B C1 ₂ F ₂ N ₂ 03 F F H CH _j CHJ Cl H CHJ H $7.64 3.84 5.73 177 179

7b c ₂ lH2 Cl ₂ N ₂ 0 _j Cl H H CHJ CHJ- CH _j CH ₃ H CH _j 63.69 5.30 5.99 186 18b

77 ^c 2i^ _j CI _j ^O _j l Cl H CHJ C"3 "3 CH ₃ H CH _j $9.36 4.82 6.47 205.5-207

78 c _2i H ₂ 3Cl ₂ FM ₂ 0 ₃ Cl F H CHJ CHJ CH _j CH _j H CH _] 61.3$ 4.8) 5.7J 204-205

7 ^C 2 _i H ₂₃ Clf ₂ N ₂ θ3 F . F H CHJ CHJ CHJ CH _j H CH _j 63.49 $.20 5.92 217.6-218

80 c _{2 |} Hi2 lFN ₂ 0 ₃ F H H CH ₃ CHJ CHJ H CH _j M 6$.31 $.13 6.21 15 160

81 ^C 2 _l H ₂ 2ClFN ₂ 0 _j F H H CH _j C"3 CH _j H H CH _j 65.31 $.11 6.26 143.5-145

82 c ₂ ,H ₂₂ C1 ₂ N ₂ 03 Cl H H CHJ CHJ CHJ H H CM _] 63.03 $.13 6.06 174 1)6

83 c ₂ ,H ₂ ,C1F ₂ N ₂ 03 F F H CHJ CHJ CHJ H H CH _j 62.96 4.61 6.01 197-198

64 c ₂ - _l H ₂₂ CI ₂ . ₂ 0 ₃ Cl H H CHJ CHJ CHJ CH _j H H 63.03 $.39 6.36 193.5-194

65 c ₂ ,H ₂ ,Cl ₂ FM ₂ 0 _j Cl F H CH _j CHJ CHJ CHJ H H 60.64 4.46 6.78 193-196

8b c ₂ ,H ₂ ,ClF ₂ N ₂ 0 _j F F H CHJ CHJ CH _j CHJ H H 62.82 4.89 6.21 182.5-184

87 c ₂ ,H2 _| C) ₃ N ₂ θ3 Cl H H CHJ CHJ CHJ CHJ Cl H $8.61 4.63 5.70 204.6-208

88 C ₂ ,H ₂₀ Cl3lN ₂ U3 F Cl H CHJ CHJ CHJ CHJ l H 56.54 4.27 6.57 21).5-219

>

89 c ₂ ,H ₂₀ CI ₂ l ₂ N ₂ θ3 F F H CHJ CH ₃ CH _j CHJ Cl H 68.43 4.27 6.66 201-202.5

\ib\t I (Continue.) BfPrmnt* tlve 1-f -Hnenoxyphenyll -flen/oyl Urei ompound

F itmpl t Moleculi r for. u '

90 C ₂ H ₂₁ C1 1"2°3 1 H H CHj CHJ CH ₃ H Cl H3 58.41 4.30 5.70 $8.47 4.30 5.63 207-2

9) C ₂ 4H ₂₀ C1 lf«2θ _j 1 H CHJ CH) CH _j H Cl CHj 56.54 3.95 5.50 $6.88 4.05 5.39 217-2

92 C ₂₄ H ₂₀ C1 ? ^r 2*2°3 H CHJ CH _j C«3 H Cl CH3 ' 58.43 4.09 $.68 58.72 4.18 5.68 221-2

93 C ₂₄ H ₂₎ Br :ι ₂ n ₂ o ₃ H CHJ CHJ C«3 CH _j Br H ! 53.75 3.95 $.22 53.72 4.03 5.53 205-2

94 C ₂₄ H ₂₀ Br( :ι ₂ f ₂ H ₂ o ₃ H CHJ CHJ CH ₃ CHJ Br H ' 53.60 3.75 $.21 53.27 3.78 5.07 198-2

95 C ₂₅ H ₂ ,CI ? ^N 2°3 H CHJ CH ₃ CH3 H CHJ CHj 1 .3.10 $.13 $.14 63.64 5.24 6.03 175-1

9b C ₂₅ H ₂₃ C1 2"2θ3 H CH ₃ CH ₃ CH _j H CHJ CHj ( .3.50 4.90 $.92 63.75 $.18 6.63 183.5

9) C ₂ 4H ₂₁ C1 ) ^N 2°3 H CH3 CH ₃ Cl H CHJ CHj 58.61 4.30 $.70 59.19 4.68 5.60

98 C ₂ 4H ₂₀ C) _? F ₂ K ₂ 0 ₃ H CHJ ca ₃ Cl H CHJ CHj ' 58.43 4.09 $.68 58.64 4.36 5.64 197.5

99 C ₂ 3H _Iβ Cl ,M ₂ θ4 H CHJ -». Cl H Cl CHj ' 53.13 3.54 $.41 $4.16 3.79 6.41 197-1

100 C ₂ 3H,,C1 ,F ₂ N ₂ 0j H CHJ CH ₃ Cl H Cl CH ₃ ' 53.11 3.34 $.4$ $3.57 3.42 5.58 207-2

101 ₂ 4H ₂ ,Br( :ι ₂ N ₂ o ₃ H CH ₃ CH ₃ CH _j H Br CH _j ! 53.76 3.76 $.22 53.96 4.04 6.20 213.5

102 ^c 24 ^H 20 ^Br ' :IF ₂ . ₂ O ₃ H CH ₃ CH ₃ CHJ H Br CHj ' 53.60 3.75 $.21 53.69 3.78 5.1b 224-2

'Ixdct mass spe trottetry.

- -

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 dimethylfora ide 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 stoc _ suspension with water. Sonication was. used where necessary to obtain a homogeneous suspension. The test procedures were as follows:

Southern Armyworm 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 applicatio'n. which lasted 25 seconds, was sufficient to wet plants to run-off. As a control, 100 milliliters of a water-acetone-emulsi ier 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 left 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 (Ephilachπa 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 ueie, closed. The" closed, dishes were labeled and held at a temperature of 80°+.5 ^β F.. for five days. Although the larvae could easily consume the left 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 ^β and a relative humidity of 50+. 5 percent, constituted the test insects.

.i = -„

_ 5 α _

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. IV. V and VI below.

Table II

Biological Properties of Representative l-(4-Phenoxyphenyl)-3-Benzoyl Urea Compounds

Compound Prepared Activity at 100 pm^ ³ ^

In Example No. SAWC^ ⁾ BB^Z ⁾

1 A* A*

2 —

3 A* A*

4 A A

5 A ^β A**

6 A° A ^β

7 A A

8 A A

9 A A

10 A* A*

11 A*. A*

12 ^* X* ^' A*

13 A ^« A*

14 A A

15 A* A*

16 A A

17 A A

18 A A

19 A A

20 A A

21 A* A*

22 A A

Table II (Continued) Biological Properties o«f Representative

1- •(4- -Phenoxyphenyl )-:ϊ-Benzoyl Urea Compounds

Compound Prepared Activity at 100 pm^ ^{3 )} In Example No. SAW^ ¹ - ⁾ MSEC ²⁾

23 A C

24 A* A*

25 A A

26 A A 27 A A 28 A A 29 A A 30 A A 31 A A 32 A A 33 A A 34 A- A* 35 A* A* 36 A* A* 37 A* A* 38 A* A* 39 A* A* 40 A* A* 41 A* A* 42 A A ^oβ 43 A 44 A A

Table II (Continued)

Biological Properti-es of Re-presentative l-(4-Phenoχyρhenyl)-3-Benzoyl Urea Compounds

Compound Prepared Activity at 100 pp ^ ³ ^

In Example No. SAW(J-) MBB^ ²

45 A* A*

46 A* A*

47 A* A*

48 A* A*

49 A A

50 A A

51 A A

52 A C

53 A . A

54 A A

55 A A

56 A A ^*

57 A A

58 A A

59 A A

60 A* A*

61 A* A*

62 A* A*

63 A* A*

64 A* A* 65 A* A* 66 A* *

Table II (Continued)

Biological Properties of Representative

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

Compound Prepared Activity at 100 ppm' ³⁾

In Example No. SA t-U MBB^ ²⁾

67 A* A*

68 A* A* 69 A* A*

70 A* A*

71 A* A*

72 A* A*

73 A* A*

74 A* A"

75 A ^« A*

76 A- A*

77 A* A*

78 A* A*

79 A* A*

80 A* A*

81 A* A"

82 A- A* 83 A* A*

84 A* A*

85 A* A*

86 A* A*

87 A ^« A*

88 A* A*

Table II (Continued) Biological Properties of Representative

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

Compound Prepared Activity at 100 pp (3) In Example No. SAW D MBB ⁽ 2 ⁾

89 A* A*

90 A* A*

91 A* A*

92 A* A*

93 A* A*

94 A* A*

95 A* A*

96 A* A*

97 A* A*

98 A* A*

99 A* A*

100 A* A*

101 A* *

102 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 500 ppm. **Tested at 6.25 ppm. "Tested at 25 ppm. o oTested at 8 ppm.

Examples 103 through 108 and Comparative Examples A through D

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

I -.

TABLE 111 (Continued)

Comparison of Representative l-(4-Phenoχvphenyl)-3-Ben.oyl Urea

Compounds with Known Compounds Against Southern Armyworm and Mexican Bean Beetle

Southern Armyworm Mexican Bean Bee 11 _

Example/ Appli tion Percent Control Application Percent Comparative Example .I .wwnd Strut turt R le (PP( (after 5 days) Rate ( pm) tit ter

From the data included in Table III. it is evident that the 1-(4-phenoxyphenyl)-3-benzoyl urea compounds of this invention provide significantly enhanced biological activity against the Southern Armyworm and 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 U.S. Patent 4.399.152. The compound of Comparative Example B was prepared in a manner similar to the procedure described in U.S. Patent 4.068.002. The compound of Comparative Example C was prepared in a manner similar to the procedure described in European Patent Application Publication No. 0069288. The compound of Comparative Example D was prepared in a manner similar to the procedure described in Japanese Patent Application 5 5038 357.

Examples 109 through 114 and Comparative Examles E through H

In order to further 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 IV below.

/

TABLE IV

Comparison of Representatlve l-(4-Phenoxyphenyl)-3-Benιpyl Urea

Compound; with Known Compounds Against Mexican fle n Beetle

Mexican Bean Beetle

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

TABLE IV (Continued)

Comparison of Representative l-(4-Phenoxyphenyl)-3-Benfoy1 Urea

Compounds with Known Compounds Against Mexican Bean Beetle

Example/ Application Percent Control Comparative Example Compound S ride t,u,re Rjte (ppffl) (fftφr 5 (fays)

From the data included in Table IV. it is evident that the l-(4-phenoxyphenyl)-3-benzoyl urea compounds of this invention provide significantly enhanced biological activity against the Mexican Bean Beetle in comparison with known compounds. As used in Table IV. the compound of Comparative Example E was prepared in a manner similar to the procedure described in U.S. Patent 4.399.152. The compound of Comparative Example F was prepared in a manner similar to the procedure described in U.S. Patent 4.005.223. The compound of Comparative Example G was prepared in a manner similar to the procedure described in U.S. Patent 4.005.223. The compound of Comparative Example H was prepared in a manner similar to the procedure described in U.S. Patent 4.041.177.

Examples 115 through 121 and Comparative Examples I through

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

TABLE V (Continued)

Comparison of Representative l-H-PhenoxyphenyP-3-penzoyl Urea

Compounds w|th Known Compounds. Against Southern Armyworm

Southern Armyworm

Example/ Application Percent Control Comparative Example _■ ompoun Stru ture Rate (ppm) (after 5 days)

From the data included in Table V,' it is evident that the l-(4-phenoxyphenyl)-3-benzoyl urea compounds of this invention provide significantly _, enhanced biological activity against the Southern Armyworm in comparison with known compounds. As used in Table V. the compound of Comparative Example I was prepared in a manner similar to the procedure described in U.S. ^' Patent 4.005.223. The compound of Comparative Example J was prepared in a manner similar to the procedure described in U.S. Patent 4.041.177. The compound of Comparative Example was prepared in a manner similar to the procedure described in Japanese Patent Application 5 6092 857.

Examples 122 through 124 and Comparative Examples L and M

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

4

From the data included in Table VI. it is evident that the l-(4-phenoxyphenyl)-3-benzoyl urea compounds of this invention provide significantly enhanced biological activity against Heliothis spp. in comparison with known compounds. As used in Table VI. the compound of Comparative Example L was prepared in a manner similar to the procedure described in U.S. Patent 4.005,223. The compound of Comparative Example M was prepared in a manner similar to the procedure described in U.S. Patent - 4.005.223.

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.