This invention relates to pesticidal polyhalo- alkene derivatives and use for combatting infestations of nematodes in soil and in plant systems, particu¬ larly agricultural crops, and for combatting plant- destructive diseases caused wholly or in part by nema¬ todes. The invention further concerns anthelmintic applications of the compounds. U.S. Patent 3,513,172 - Brokke and divisional patents thereof disclose nematicidal trifluorobutenyl derivatives of the formula

F ₂ C=CFCH ₂ CH ₂ -R

where R is se'lected from various substituents includ¬ ing some heterocyclics such as 2-thio-4-alkylthia- zolyl. These and other patents reflect ongoing efforts of industry and governmental agencies to find a ⁿ d commercialize chemicals for combatting nematodes and nematode-induced plant diseases, to thereby reduce the substantial economic losses resulting from nematode infestations.

A new class of polyhaloalkene derivatives has now been found having high nematicidal activity and good soil mobility. In addition, the compounds exhibit control of a variety of nematodes, and in some cases systemic activity. The compounds also are effective against helminths that are indicators of animal anthelmintic activity.

The novel nematicidal compounds of the invention are polyhaloalkene derivatives of the formula (I):

wherein X is sulfur, oxygen, nitrogen or methylene, Y 1 and Y2 independently are fluorine, chlorine or bromine, Z is hydrogen or the same as Y 1 or Y2, and n is 1-4, preferably 1 or 2; provided that: (A) when X is. sulfur, R is thiazolyl, optionally substituted thienyl, optionally substituted thia- naphthyl, optionally substituted thiazolinyl, option¬ ally substituted thiadiazolyl, optionally substituted oxadiazolyl or 3,4,4-trifluoro-3-butenyloxycarbonyl- methyl;

(B) when X is oxygen, R is C(0)R wherein R is perfluoroalkyl, optionally substituted phenyl, optionally substituted thienyl, optionally substituted furanyl, optionally substituted pyrrolyl or dihydro- thiazolylthiomethyl;

(C) when X is nitrogen, R taken with the nitro¬ gen is .an isothiocyanate, succinimide or saccharine group; and

(D) when X is methylene, R is hydroxy. Other aspects of the invention include methods of controlling nematode populations and arresting plant and animal diseases caused by nematodes and helminths, and nematicidal and anthelmintic formulations based on the polyhaloalkene derivatives. Typical nematode species controlled in accordance with the invention are the root-knot, stunt, lesion, cyst and C. elegans nematodes.

In subclasses A and B of the compounds of formula I above, available carbon atoms of the heterocyσlic rings other than thiazolyl optionally may be substi¬ tuted with any group or groups which are non-destruc-

tive of the nematicidal or anthelmintic activity of the compounds. Typical substituents include alipha¬ tic, aromatic and heterocyclic groups, halo, nitro, cyano, alkoxy, alkylthio, haloalkyl, haloalkoxy, halo-, nitro-, cyano- or alkoxy-substituted phenyl, polyhaloalkenylthio, phenylalkylthio, phenylthioalkyl- thio, propargylthio, cycloalkylmethylthio, and the like, further including straight and branched chain structures, and the various isomers of such substi- tuents.

Throughout this specification the alkyl, alkenyl and alkynyl groups may contain 1-11 or more carbon atoms and may be straight. chain or branched. Cyclo- alkyl groups may contain 3-8 or more carbon atoms. Preferably, alkyl, alkenyl, alkynyl and alkoxy are lower alkyl, lower alkenyl, lower alkynyl or lower alkoxy, meaning that these groups contain 1-8 carbon atoms, more preferably 1-4 carbon atoms such as methyl, propenyl and methoxy. Halo or halogen means fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine. Aromatic substituents include 'phenyl, naphthyl, anthracene, diphenyl, and the like.

Representative compounds of formula I are listed in Tables 1, la, lb and lc appended.

The preferred compounds of formula I are those of subclass A wherein R is defined as follows: (1) R is a thiadiazolyl group of the structure:

2, 4-thiadiazol-5-yl 1 , 2, 4-thiadiazol-3-yl

2 wherein R is 3, 4, 4-trifluoro-3-butenyl, or a phenylmethyl or phenylthiomethyl group each.

optionally substituted with halogen or nitro.

2 The R S- group may be in the 3- or 5-position of the 1, 2,4-thiadiazole ring;

(2) R is a thiadiazolyl group as in (1) above but

2 with lodo in place of R S;

(3) R is a thiadiazolyl group of the structure:

³ N N ^1* '[ ⁵ l,3,4-thiadiazol-5-yl

3 ^s R ^J i

3 wherein R is aryl, ^■ arylalkyl, aryloxyalkyl, alkylthio, haloalkylthio, cyanoalkylthio, aryl- alkylthio, aryloxyalkylthio, arylthioalkylthio, heterocycloalkylthio, alkenylthio, haloalkenyl- thio, halocycloalkylalkenylthio, or an amino group mono- or disubstituted with members selected independently from alkyl, alkylcarbonyl, haloalkylcarbonyl, aryl, arylaminocarbonyl, aryl- alkylcarbonyl, arylalkoxycarbonyl and 3-(2,2-di- chloroethenyl)-2,2-dimethylcyclopropanecarbony1;

(4) R is an oxadiazolyl group of the structure:

l,2,4-oxadiazol-5-yl or 1, 2, 4-oxadiazol-3-yl

4 wherein R is aryl or arylalkyl substituted with chloro, fluoro, alkyl, haloalkyl, alkoxy, or

4 nitro. The R group may be in the 3- or 5- position of the 1, 2, 4-oxadiazole ring; or

(5) R i ^' s an oxadiazolyl group of the structure:

1,3, 4-oxadiazol-5-yl

wherein R is alkyl, haloalkyl, aryl, aryl¬ alkyl, aryloxyalkyl, arylthioalkyl, heterocyclo- alkyl, arylalkenyl or alkynyl ( ^G 2~ ^C ₁ 1^* Aryl and the heterocycles described in (3) and (4) above are optionally substituted with one or more groups selected independently from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, cyano, nitro and phenyl. Aryl and the heterocycles described in (5) above are optionally substituted with one or more groups selected independently from halogen, alkyl, alkoxy, nitro, amino, hydroxy, acetyloxy and alkylaminocarbonyloxy. (6) R is a thiazolyl group.

Synthesis The compounds of formula I are prepared in a known manner. For example, a polyhaloalkene such as 4-bromo-l, 1, 2-trifluoro-1-butene is reacted with a mercaptothiazole (prepared by reaction of thiazole and elemental sulfur) or mercaptothiazoline in a reaction solvent medium containing sodium ethoxide to form the thiazolyl or thiothiazoline derivative of the poly¬ haloalkene. Examples 1, 2, 8-14, 16 and 17 below are representative of this and other reaction schemes for synthesis of the subclass A compounds of formula I (x = sulfur). Compounds of formula I wherein X is oxygen (subclass B) may be prepared as described in Examples 3 and 4. Similarly, the subclass C (X = nitrogen) and subclass D compounds (X = -CH_-) are prepared as described in Examples 5 and 6 (subclass C) and 7 (subclass D) .

Other polyhaloalkenes may be used in known ways to prepare other compounds of formula I. For example, trifluoroethylene can be chain-extended with methyl dibromide and the 1-, 3-dibromo-l, 1, 2-trifluoropropane product then reacted with a mercaptan to form a thio

/ S86/01284

-6-

intermediate. The intermediate is then dehydrohalo- genated, as follows, wherein "BP" is benzoyl peroxide and "DBU" is 1, 8-diazabicyclo[5.4.0]undec-7-ene catalyst, as described by Tarrant and Tandon, J. Org. Chem. 34(4), 864 (1969) : CF ₂ Br

CH ₂ CH CF ₂ Br

Dihalopropene derivatives within the scope of formula I may- be prepared by the following general

1 2 reaction, wherein Y and Y are as defined above

1 2 and one of Y and Y also may be hydrogen:

_7_

Trihalopropene derivatives also may be prepared in a manner and reaction similar to the Tarrant and Tandon scheme to form other compounds of formula I, wherein Y and Z are as defined in formula I

Methods of preparing propenes, butenes and other alkenes having mixed halogen substituents and there¬ fore useful in the invention for preparing compounds of formula I are described in a Ph.D. thesis of M. R. Lillyguist, University of Florida (1955), pages 9, 39, 59 and 60. It will be apparent, therefore, that the polyhaloalkenes and heterocyclic or other compounds used to prepare the compounds of formula I generally are known materials or can be synthesized by known procedures.

The following examples further describe methods of preparing the compounds of the invention. In the examples all parts and percentages are by weight and all temperatures are "C unless otherwise stated. The

products of Examples 1-9 correspond to compounds 1-9 listed in Tables 1 and lb. Examples 10-17 identify the tabulated compounds to which they relate.

Example 1 2-(3, 4, 4-Trifluoro-3-butenylthio)-

4, 5-dihydrothiazole Sodium ethoxide was prepared by stirring 0.25 gram (0.011 mole) of sodium metal in 30 ml of absolute ethanol. To this was added 1.2 grams (0.01 mole) of 2-mercaptothiazoline. The reaction mixture was stirred for one hour and the excess ethanol was removed under reduced pressure. The residue was dis¬ solved in 35 ml of methyl ethyl ketone and 2.0 grams (0.01 mole) of 4-bromo-l, 1,2-trifluoro-1-butene was added. The reaction mixture was stirred at ambient temperature for four hours, then concentrated under reduced pressure to a residue. The residue was dissolved in 50 ml of toluene and washed with three 25 ml portions of water. The organic layer was dried with sodium sulfate and filtered. - The filtrate was concentrated under reduced pressure to give 1.7 grams of 2-( 3, 4,4-trifluoro-3-butenylthio)-4, 5-dihydrothia- zole as an oil. The nmr and the ir spectra were consistent with the proposed structure. Example 2

5-Methylthio-2-(3,4,4-trifluoro- 3-butenylthio)-1,3, 4-thiadiazole A solution of 2.0 grams (0.012 mole) of 2-mer- capto-5-methylthio-l,3,4-thiadiazole in 25 ml of distilled acetone was added to a stirred mixture of

0.84 gram (0.006 mole) of potassium carbonate and 0.2 gram (0.001 mole) of potassium iodide in 25 ml of distilled acetone. With continued stirring 2.2 grams (0.012 mole) of 4-bromo-l, 1,2-trifluoro-1-butene was added dropwise. Upon completion of addition the reac¬ tion mixture was heated under reflux for four hours.

- 9 -

The reaction mixture was cooled, filtered, and the filtrate concentrated under reduced pressure to a residue. The residue was dissolved in diethyl ether and washed with aqueous 5% sodium hydroxide. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to give 1.3 grams of 5-methylthio-2-( 3, 4, 4- trifluoro-3-butenylthio) -1, 3, 4-thiadiazole as an oil. The nmr and the ir spectra were consistent with the proposed structure.

Example 3 (3,4, 4-Trifluoro-3-butenyl) heptafluorobutyrate

(A) A stirred solution of 2.6 ml (0,02 mole) of heptafluorobutyric acid in 50 ml of water was warmed to 50°C and 5.1 grams (0.022 mole) of silver oxide was added. Upon completion of addition the reaction mixture temperature was maintained at 50-60°C for two hours. The reaction mixture was allowed- to cool to -ambient temperature, then it was filtered. The filtrate was concentrated under reduced pressure to give 6.4 grams of the silver salt of heptafluoro¬ butyric acid as a solid.

(B) To a stirred mixture of 3.2 grams (0.01 mole) of the silver salt of heptafluorobutyric acid in 40 ml of diethyl ether was added dropwise 1.9 grams

(0.01 mole) of 4-bromo-l, 1, 2-trifluoro-1-butene in 10 ml of diethyl ether. Upon completion of addition the reaction mixture was stirred for two hours at ambient temperature, then was heated under reflux for one hour. The ether solvent was removed by distillation and the residual oil distilled under reduced pressure to give 1.0 gram of ( 3, 4, 4-trifluoro-3-butenyl) heptafluorobutyrate; b.p. 25°C/4.θ ^' mm Hg. The nmr spectrum was consistent with the proposed structure.

1 84

- 10 -

Example 4 ( 3, 4, 4-Trifluoro-3-butenyl) 4-chlorobenzoate To a stirred solution of 1.6 grams (0.01 mole) of 4-chlorobenzoic acid in 35 ml of acetonitrile was added 1.5 ml (0.01 mole) of 1, 8-diazabicyclo[5.4.0]- undec-7-ene, followed by 1.9 grams (0.01 mole) of 4-bromo-l, 1, 2-trifluoro-1-butene. The reaction mixture was heated under reflux for four hours then allowed to cool to ambient temperature. Water, 25 ml, was added to the reaction mixture, and the reaction mixture was extracted with three 20 ml portions of diethyl ether. The combined extracts were washed in succession with one 25 ml portion of water, two 25 ml portions of aqueous 5% sodium hydroxide and, finally, one 25 ml portion of water. The organic layer was dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to give 1.2 grams of ( 3, 4,4-trifluoro-3-butenyl) 4-chlorobenzoate as an oil. The nmr and the ir spectra were consistent with the proposed structure.

Example 5 • N-( 3, 4,4-trifluoro-3-butenyl)succinimide This compound was prepared in a manner analogous to that of Example 1 using 1.1 grams (0.01 mole) of succinimide, 1.9 grams (0.01 mole) of 4-bromo-l, 1, 2- trifluoro-1-butene, 0.25 gram (0.01 mole) -of sodium metal, 30 ml of absolute ethanol and 20 ml of di- methylforma ide. The yield of N-( 3, 4,4-trifluoro-3- butenyl)succinimide was 0.3 gram as an oil. The nmr and the ir spectra were consistent with the proposed structure.

Example 6 (3,4, 4-Trifluoro-3-butenyl) isothiocyanate (A) To a stirred solution of 10.0 grams (0.053 mole) of 4-bromo-l, 1, 2-trifluoro-1-butene in 50 ml of

- 11 - ^•

dimethylformamide was added 10.4 grams (0.056) of the commercially available potassium salt of phthalimide. The reaction mixture was warmed to 50°C where it stirred for four hours. The reaction mixture was allowed to cool and 50 ml of chloroform was added. The mixture was poured into 200 ml of water. The aqueous layer was separated and extracted with two 50 ml portions of chloroform. The combined organic layers were washed with two 50 ml portions of aqueous 5% sodium hydroxide and one 50 ml portion of water. The organic layer was dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to give 4.8 grams of N-(3,4, 4-trifluoro-3- butenyDphthalimide as an oil. The nmr spectrum was consistent with the proposed structure.

(B) A stirred solution of 4.2 grams (0.016 mole) of N-( 3, 4, 4-trifluoro-3-butenyl)phthalimide and 1.0 ml (0.032 mole) of anhydrous hydrazine in 50 ml of methanol was heated under reflux for one hour. The reaction mixture was allowed to cool and the solvent removed under reduced pressure. The residue was taken up in 25 ml of water and 30 ml of concentrated hydro¬ chloric acid. The reaction mixture was heated under reflux for two hours and then cooled to 0°C. A solid _was removed from the reaction mixture by filtration. The filtrate was concentrated under reduced pressure to a residue. The residue was taken up in 50 ml of water and made basic with aqueous 10% sodium hydroxide. The mixture was extracted with two 25 ml portions of diethyl ether. The combined extracts were dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to give 0.4 gram of 4-amino-l, 1,2-trifluoro-1-butene as an oil. The ir spectrum was consistent with the proposed structure.

- 12 -

(C) A stirred solution of 0.4 gram (0.004 mole) of 4-amino-l, 1, 2-trifluoro-1-butene in 25 ml of diethyl ether was saturated with gaseous hydrochloric acid. The reaction mixture was concentrated under reduced pressure to give 0.4 gram of 4-amino-l, 1, 2- trifluoro-1-butene hydrochloride as a solid. The nmr spectrum was consistent with the proposed structure.

(D) To a stirred solution of 0.4 gram (0.0027 mole) of 4-amino-l, 1, 2-trifluoro-1-butene hydrochlo- ride in 15 ml of chloroform was added 0.3 gram (0.003 mole) of thiophosgene, followed by 0.7 ml (0.009 mole) of triethylamine. Upon completion of addition the reaction mixture was stirred at ambient temperature for three hours. The reaction mixture was then washed in succession with one 25 ml portion of water, two 25 ml portions of aqueous 5% sodium hydroxide, and, finally, one 25 ml portion of water. The organic layer was dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to give 0.3 gram of ( 3, 4, 4-trifluoro-3-butenyl) isothio- cyanate as an oil. The ir spectrum was consistent with the proposed structure.

Example 7 4, 5, 5-Trifluoro-4-penten-l-ol (A) To a stirred mixture of 2.4 grams (0.1 mole) of magnesium turnings in 100 ml of diethyl ether was added 18.9 grams (0.1 mole) of 4-bromo-l, 1, 2-tri- fluoro-1-butene. Upon completion of addition the reaction mixture was heated under reflux until the reaction was complete. The reaction mixture was cooled to 0 ^β C and 9.0 grams (0.2 mole) of carbon dioxide was bubbled in slowly. Upon completion of addition the reaction mixture was stirred for one hour, then 100 ml of aqueous 20% hydrochloric acid was added to destroy the excess magnesium. The reaction

- 13 -

mixture was extracted with three 40 ml portions of diethyl ether. The combined extracts were cooled and 40 ml of aqueous 25% sodium hydroxide was added slowly. The organic layer was separated and extracted with one 40 ml portion of aqueous 25% sodium hydroxide. The combined base layers were cautiously acidified with aqueous 20% hydrochloric acid. The mixture was extracted with two 100 ml portions of diethyl ether. . The combined extracts were dried with sodium sulfate and filtered. The filtrate was con¬ centrated under reduced pressure to give 6.9 grams of 4, 5, 5-trifluoro-4-pentenoic acid as an oil. The nmr and ir spectra were consistent with the proposed structure. (B) To a stirred suspension of 0.4 gram (0.01 mole) of lithium aluminum hydride in 20 ml of diethyl ether was added dropwise a solution of 1.5 grams (0.01 mole) of 4, 5, 5-trifluoro-4-pentenoic acid in 30 ml of diethyl ether. Upon completion of addition the reac- tion mixture was stirred at ambient temperature for one hour, then 20 ml of water was added carefully. The mixture was filtered and the filtrate concentrated under reduced pressure to give 0.8 gram of 4, 5,5-tri- fluoro-4-penten-l-ol as an oil. The nmr and the ir spectra were consistent with the proposed structure.

Example 8 3-Chloro-5-( 3, 4, 4-trifluoro-3- butenylthio)-l, 2,4-thi diazole (A) A stirred solution of 5.0 grams (0.026 mole) of dipotassium cyanoimidodithiocarbonate [prepared by the method. of L.S. Wittenbrook et al, J. Org. Chem. , 38, 3, 465 (1973)] in 19 ml of acetone and 22 ml of water was cooled to 0°C and 4.9 grams (0.026 mole) of 4-bromo-l, 1, 2-trifluoro-1-butene in 10 ml of acetone was added dropwise. Upon completion of addition the

- 14 -

reaction mixture was allowed to warm to ambient tem¬ perature where it stirred for 16 hours. The reaction mixture was concentrated under reduced pressure to a residual solid. The solid was dissolved in ethyl acetate and filtered. The filtrate was concentrated under reduced pressure, and the residual solid dried in a vacuum oven. The dried solid was dissolved in hot chloroform - ethyl acetate and filtered. The filtrate was concentrated under reduced pressure, and the residual solid dried in a vacuum oven to give 4.4 grams of potassium ( 3,4, 4-trifluoro-3-butenyl) cyano¬ imidodithiocarbonate. The nmr spectrum was consistent with the proposed structure.

(B) A stirred solution of 2.0 grams (0.008 mole) of potassium ( 3, 4, 4-trifluoro-3-butenyl) cyanoimido¬ dithiocarbonate in 10 ml of chloroform was cooled to 0°C'and 1.2 grams (0.009 mole) of sulfuryl chloride was added dropwise. Upon. completion of addition the reaction mixture was maintained at 0°C for one hour, warmed under reflux for 4 hours, then at ambient temperature for 16 hours. Stirring was continued throughout the 21 hour period. The reaction mixture was filtered and the filtrate concentrated under reduced pressure. The concentrate was passed through silica gel using diethyl ether as an eluent. The ether eluate was filtered and the -filtrate concen¬ trated under reduced pressure to a residual oil. The oil was dried in a vacuum oven to give 0.9 gram of 3-chloro-5-( 3,4,4-trifluoro-3-butenylthio)-1, 2, 4-thia- diazole. The nmr and the ir spectra were consistent with the proposed structure.

Example 9

3-Bromo-5-( 3, 4, 4-trifluoro-3-butenyl thio)-l, 2, 4-thiadiazole A stirred solution of 3.0 grams (0.011 mole) of

- 15 -

potassium ( 3, 4,4-trifluoro-3-butenyl) cyanoimido¬ dithiocarbonate (prepared as in Example 8, Step A) in 25 ml of water was cooled to 0°C and 2.2 grams (0.014 mole) of bromine was added dropwise under a positive gaseous nitrogen pressure. Upon completion of addi¬ tion the reaction mixture temperature was maintained at 0°C for one hour, then was allowed to warm to ambient temperature where it stirred for 16 hours. Sodium thiosulfate was added to the reaction mixture, which was then partitioned between chloroform and additional water. The chloroform layer was separated and dried with magnesium sulfate. The mixture was filtered and concentrated under reduced pressure to a residual oil. The oil was passed through silica gel using 4:1 - hexane :diethyl ether as an eluent. The eluate was concentrated under reduced pressure to give 1.1 grams of 3-bromo-5-( 3, 4,4-trifluoro-3-butenyl- thio) -1, 2, 4-thiadiazole as an oil. The nmr spectrum was consistent with the proposed structure. Example 10 (Compound 25)

3, 5-Di( 3,4,4-Trifluoro-3-butenylthio)- 1, 2, 4-thiadiazole

(A) A stirred solution of 16.0 grams (0.08 mole) of dipotassium cyanoimidodithiocarbonate (prepared as in Example 8, Step A) and 2.6 grams (0.08 mole) of sulfur in 425 ml of methanol was heated under reflux for 15 minutes. The reaction mixture was allowed to cool then was concentrated under reduced pressure to a residual solid. The solid was dried under reduced pressure to yield 18.1 grams of the dipotassium salt of 3, 5-dimercapto-l, ,4-thiadiazole.

(B) A solution of 1.0 gram (0.004 mole) of the dipotassium salt of 3, 5-dimercapto-l, 2,4-thiadiazole in 35 ml of methyl ethyl ketone was stirred and 1.7 grams (0.009 mole) of 4-bromo-l, 1, 2-trifluoro-1-butene

- 16 -

was added. The reaction mixture was heated under reflux for two hours then allowed to cool to ambient temperature where it stirred for 18 hours. The reaction mixture was concentrated under reduced pressure to a residue. The residue was stirred in 25 ml of water and the mixture was extracted with two 25 ml portions of toluene. The organic layer was dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to yield 1.1 grams of 3, 5-di-(3,4, -trifluoro-3-butenylthio)-1, 2, 4-thia- diazole as a liquid. The nmr spectrum was consistent with the proposed structure.

Example 11 (Compound 26) 3-(4-Nitroρhenylmethylthio)-5-( 3, 4, 4- trifluoro-3-butenylthio)-1, 2, 4-thiadiazole

(A). A stirred solution of 24.7 grams (0.109 mole) of the dipotassium salt of 3., 5-d.imercapto- 1, 2, 4-thiadiazole (prepared as in Example 10, Step A) in 200 ml of water was acidified with concentrated hydrochloric acid. The resultant solid was collected by filtration to yield 17.3 grams of wet 5-amino- l,2,4-dithiazol-3-thione; m.p. 217-220°C.

(B) A solution of 2.2 grams (0.055 mole) of sodium hydroxide in 7 ml of water and 20 ml of ethanol was stirred and 4.0 grams (0.027 mole) of 5-amino-

1, 2, 4-dithiazol-3-thione was added portionwise. After all of the 5-amino intermediate was in solution, 4.7 grams (0.027 mole) of 4-nitrophenylmethyl chloride was added dropwise. Upon completion of addition the reac- tion mixture was stirred at ambient temperature for 16 hours. The reaction mixture was concentrated under reduced pressure to a residue. The residue was dis¬ solved in 20 ml of water then extracted with two 25 ml portions of diethyl ether. The aqueous layer was acidified with concentrated hydrochloric acid to yield

- 17 -

a gummy solid. The solid was extracted from the aqueous layer with two 25 ml portions of ethyl acetate. The combined extracts were dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to yield a gummy solid. The solid was dissolved in methylene chloride and filtered to remove a small amount of insoluble material. The filtrate was concentrated under reduced pressure to yield 2.8 grams of 3-(4-nitrophenylmethylthio)-5-mer- capto-1, 2, 4-thiadiazole as a solid. The nmr spectrum was consistent with the proposed structure.

(C) A solution of 0.25 gram (0.011 mole) of sodium in 35 ml of ethanol was stirred and 2.7 grams (0.0095 mole) of 3-(4-nitrophenylmethylthio) -5-mer- capto-1, 2, 4-thiadiazole was added. Upon completion of addition the reaction mixture was stirred at ambient temperature for one hour. The ethanol solvent was removed under reduced pressure. The residue was dis¬ solved in 35 ml of methyl ethyl ketone and 1.6 grams (0.0085 mole) of 4-bromo-l, 1, 2-trifluoro-1-butene was added. Upon completion of addition the reaction mixture was stirred for 16 hours, then was concen¬ trated under reduced pressure to a residue. The residue was dissolved in 50 ml of toluene and washed with 25 ml of water, two 25 ml portions of aqueous 5% sodium hydroxide solution, and 25 ml of water. The organic layer was dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to yield a residual oil. The oil was dis- solved in methylene chloride and passed through a column of silica gel. The eluate was concentrated under reduced pressure to yield 2.1 grams of 3-(4- nitrophenylmethylthio)-5-(3, 4, 4-trifluoro-3-butenyl- thio)-l, 2,4-thiadiazole. The nmr spectrum was coti- sistent with the proposed structure.

- 18 -

Example 12 (Compound 30) 2-(l-Methylethylthio)-5-(3,4,4-trifluoro-3- butenylthio) -1,3,4-thiadiazol.e A solution of 22.5 grams (0.15 mole) of 2,5-di- mercapto-1, 3, 4-thiadiazole in 200 ml of tetrahydro¬ furan was stirred and 21 ml (0.15 mole) of triethyl- amine was added dropwise. Upon completion of addition the reaction mixture was stirred at ambient tempera¬ ture for 15 minutes, then 28.4 grams (0.15 mole) of 4-bromo-l, 1,2-trifluoro-1-butene was added dropwise. Upon completion of addition the reaction mixture was heated under reflux for two hours. The cooled reac¬ tion mixture was concentrated under reduced pressure to a residue. The residue was stirred in 250 ml of diethyl ether and extracted with two 100 ml portions of aqueous 10% potassium hydroxide. The combined extracts were acidified with aqueous 10% hydrochloric acid, then were extracted with two 100 ml portions of diethyl ether. The combined ether extracts were dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to yield, after drying, 35.6 grams of 2-mercapto-5-( 3, 4,4-tri- fluoro-3-butenylthio)-1, 3,4-thiadiazole as a solid. The nmr spectrum was consistent with the proposed structure.

(B) In a manner analogous to Example 11, Step C, 1.3 grams (0.005 mole) of 2-mercapto-5-( 3, 4,4-tri- fluoro-3-butenylthio)-l, 3,4-thiadiazole, 0.5 ml (0.005 mole) of 2-iodopropane, 0.15 gram (0.007 mole) of sodium were reacted in 35 ml of ethanol and 35 ml of methyl ethyl ketone by heating the mixture under reflux for five hours prior to stirring at ambient temperature for 16 hours. The yield of 2-(l-methyl- ethylthio)-5-(3,4,4-trifluoro-3-butenylthio)-l, 3,4- thiadiazole was 1.3 grams as a liquid. The nmr spectrum was consistent with the proposed structure.

- 19 -

Example 13 (Compound 37)

2-(4-Chlorophenyl)-5-( 3, 4,4-trifluoro-

3-butenylthio)-1, 3, 4-thiadiazole

(A) A stirred solution of 8.1 grams (0.048 mole) 5 of 4-chlorobenzoic acid hydrazide in 300 ml of tri- ethyl orthoformate was heated under reflux for 16 hours. The excess triethyl orthoformate was removed by distillation and the residual solid was stirred with petroleum ether to yield 7.7 grams of 2-(4- 10 chlorophenyl)-l, 3, 4-oxadiazole; m.p. 129°C. The nmr spectrum was consistent with the proposed structure.

(B) Under a nitrogen atmosphere, a solution of 17 grams (0.084 mole) of phosphorus pentasulfide in 100 ml of dry xylene was stirred and 7.6 grams (0.042

• _j c mole) of 2-(4-chlorophenyl)-1, 3, 4-oxadiazole was added. Upon completion of addition the reaction mixture was heated under reflux for 30 hours-. The reaction mixture was cooled and 100 ml of water was added dropwise. The mixture was filtered through

20 diatomaceous earth to separate the organic and aqueous phases. The organic phase (the filtrate) was extracted with an aqueous 10%" potassium hydroxide- solution. The extract was acidified with an aqueous 5% hydrochloric acid solution, and then was extracted

25 with diethyl ether. The ether extract was concen¬ trated under reduced pressure to yield 0.3 gram of 2-(4-chlorophenyl)-5-mercapto-l, 3,4-thiadiazole; m.p. 178°C.

(C) In a manner analogous to Example 2, 0.3 gram 30 (0.0015 mole) of 2-(4-chlorophenyl)-5-mercapto-l, 3,4- thiadiazole, 0.4 gram (0.002 mole) of 4-bromo-l, 1, 2- trifluoro-1-butene, 0.2 gram (0.0015 mole) of potas¬ sium carbonate, and 0.05 gram of potassium iodide were reacted in 9 ml of methyl ethyl ketone. The yield of 35 2-(4-chlorophenyl)-5-( 3, 4, 4-trifluoro-3-butenylthio)-

- 20 -

1, 3, 4-thiadiazole was 0.1 gram; m.p. 68-69°C. The nmr spectrum was consistent with the proposed structure. Example 14 (Compound 39) 3-(4-Chlorophenyl)-5-( 3, 4, 4-trifluoro-3- butenylthio)-l, 2,4-oxadiazole

(A) A stirred solution of 4.1 grams (0.03 mole) of 4-σhlorobenzonitrile, 2.1 grams (0.03 mole) of hydroxylamine hydrochloride, and 2.1 grams (0.015 mole) of potassium carbonate in 10 ml of water and 100 ml of ethanol was heated under reflux for 16 hours.

The reaction mixture was cooled and 50 ml of water was added. The ethanol solvent was removed under reduced pressure. The concentrate was cooled in an ice bath and the resultant solid collected by filtration. The solid was dried to yield 4.4 grams of N-hydroxy- imido-4-chlorobenzamide; m.p. 122-130°C.

(B) A solution of 4.4 grams (0.028 mole) of N-hydrσxyiraido-4-chlorobenzamide in 50 ml of diethyl ether was stirred and 0.55 ml (0.007 mole) of thio- phosgene was added dropwise. Upon completion of addi¬ tion the reaction' mixture was stirred at ambient temperature for 15 minutes then was heated under reflux for one hour. The reaction mixture was cooled and filtered to collect bis 0, 0'-thiocarbonyl(4- chloro-N-hydroxybenzenecarboximidamide) . A 100% yield was assumed.

(C) A solution of 10.0 grams (0.25 mole) of sodium hydroxide in 90 ml of water was stirred and 5.4 grams (0.14 mole) of bis 0, 0'-thiocarbonyK4-chloro- N-hydroxybenzenecarboximidamide) was added. Upon completion of addition the reaction mixture was heated under reflux for one hour. The reaction mixture was cooled and extracted with two 50 ml portions of diethyl ether. The aqueous layer was acidified with concentrated hydrochloric acid. The resultant preci-

- 21 -

pitate was collected by filtration, washed with water, and dried to yield 1.0 gram of 3-(4-chlorophenyl)-5- mercapto-1, 2, 4-oxadiazole; m.p. 139-156°C, dec. The nmr spectrum was consistent with the proposed struc- ture.

(D) In a manner analogous to Example 2, 0.7 gram (0.003 mole) of 3-(4-chlorophenyl)-5-mercapto-l, 2, 4- oxadiazole, 0.6 gram (0.003 mole) of 4-bromo-l, 1, 2- trifluoro-1-butene, 0.2 gram (0.0015 mole) of potassium carbonate, and 0.1 gram of potassium iodide were reacted in 40 ml of distilled acetone. The yield of 3-(4-chlorophenyl)-5-( 3,4, 4-trifluoro-3-butenyl- thio)-1, 2, 4-oxadiazole was 0.3 gram; m.p. 49-52°C. The nmr spectrum was consistent with the proposed structure.

Example 15 (Compound 43) 5-(3-4,4-Trifluoro-3-buten.ylthio) -1, 3,4-oxadiazole

(A) A solution of 25 grams (0.147 mole) of 4-chlorophenylacetic acid in 250 ml of acetonitrile was stirred and 15.0 grams (0.0147 mole) of bromo- ethane, followed by 22.0 grams (0.147 mole) of 1, 8-diazabicyclo[5.4.0]undec-7-ene, were added. Upon completion of addition the reaction mixture was cooled in a water bath while being stirred for 18 hours. The reaction mixture was concentrated under reduced pres¬ sure to one-half volume and then was added to 50 ml of water. The mixture was extracted with two portions of diethyl ether. The combined extracts were dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to yield 18.2 grams of ethyl (4-chlorophenyl)acetate.

(B) A stirred solution of 18.2 grams (0.091 mole) of ethyl (4-chlorophenyl)acetate and 10 ml of hydrazine hydrate in 10 ml of ethanol was heated under reflux for one hour during which time a solid preci-

pitated. The solid was collected by iltration to yield, ^' when dried, 14.9 grams of 4-chlorophenylacetic acid hydrazide; m.p. 159-161°C. The nmr spectrum was consistent with the proposed structure. (C) A stirred solution of 7.0 grams (0.038 mole) of 4-chlorophenylacetic acid hydrazide, 3.0 grams (0.039 mole) of carbon disulfide and 2.8 grams (0.050 mole) of potassium hydroxide in 10 ml of water and 200 ml of ethanol was heated under reflux for four hours. The ethanol was removed Under reduced pressure. The concentrate was taken up in water and the mixture washed with diethyl ether. The aqueous layer was acidified with aqueous 5% hydrochloric acid and then was extracted with diethyl ether. The extract was dried with magnesium sulfate and filtered. ^* The filtrate was concentrated under reduced pressure to yield 3.9 grams of 2-(4-chlorophenylmethyl)-5-mer- capto-1, 3, 4-oxadiazole; m.p. 115°C. The nmr spectrum was consistent with the proposed structure. (D) In a manner analogous to Example 2, 2.4 grams (0.011 mole) of 2-(4-chlorophenylmethyl)- 5-mercapto-l, 3,4-oxadiazole, 2.0 grams (0.011 mole) of 4-bromo-l, 1, 2-trifluoro-1-butene, 1.5 grams (0.011 mole) of potassium carbonate and 0.5 gram of potassium iodide were reacted in 45 ml of acetone. The yield of 2-(4-chlorophenylmethyl)-5-( 3,4, 4-trifluoro-3-butenyl- thio)-l, 3, 4-oxadiazole was 1.5 grams as a liquid. The nmr spectrum was consistent with the proposed struc¬ ture. Example 16 (Compound 230)

Synthesis of 2-(3, 4,4-trifluoro-3- butenylthio) hiazole Under a nitrogen atmosphere, a stirred solution of 2.0 grams (0.024 mole) of thiazole in 30 ml of dry tetrahydrofuran is cooled to -65°C and 16 ml of 1.55

-23-

molar n-butyllithium is added dropwise. Upon comple¬ tion of addition the reaction mixture is stirred for 45 minutes and 0.8 gram (0.024 mole) of elemental sulfur is added portionwise. The reaction mixture is stirred for an additional one hour, the temperature then being adjusted to -60°C, and 4.5 grams (0.024 mole) of 4-bromo-l, 1, 2-trifluoro-1-butene is added dropwise. Upon completion of addition the reaction mixture is stirred for three hours during which time it is allowed to warm to ambient temperature. The solvent is removed under reduced pressure. The resi¬ due is dissolved in diethyl ether and washed with two portions of an aqueous solution saturated with sodium chloride. The organic layer is dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure to a residual semi-solid. The semi-solid is subjected to column chromatography on silica gel. Elution is accomplished with 1:1 - hexane:diethyl ether. The appropriate fractions are combined and concentrated under reduced pressure to give 0.4 gram of 2-(3, 4, 4-trifluoro-3-butenylthio) thiazole as an oil. The nmr and ir spectra are con¬ sistent with the proposed structure.

Example 17 (Compound 231) Synthesis of 2-(2, 3, 3-trifluoro-2- propenylthio)thiazole (A) A stainless steel autoclave is charged with 50 grams (0.6 mole) of trifluoroethylene, 300 grams (1.7 moles) of dibromomethane, and 5 grams (0.02 mole) of benzoyl peroxide. The reaction mixture is stirred and heated at 100°C for six hours, then is cooled to -70 ^β C. The autoclave is opened and the reaction mixture fractionally distilled. The appropriate frac¬ tions are combined to give 1, 3-dibromo-l, 1, 2-tri- fluoropropane.

-24-

(B) Under a nitrogen atmosphere a stirred solu¬ tion of 20 grams (0.24 mole) of thiazole in 300 ml of dry tetrahydrofuran is cooled to -65°C and 160 ml of n-butyllithium (1.55 molar) is added dropwise. Upon completion of addition the reaction mixture is stirred for 45 minutes and 8.0 grams (0.24 mole) of elemental sulfur is added portionwise. Upon completion of addi¬ tion the reaction mixture is stirred for one hour and, at -60°C. 61.4 grams (0.24 mole) of 1,3-dibromo- 1, 1, 2-trifluoropropane is added dropwise. Upon com¬ pletion of addition the reaction mixture is allowed to warm to ambient temperature where it stirs for three hours. The reaction mixture is concentrated under reduced pressure to a residue. The residue is dis- solved in diethyl ether and is washed with two por¬ tions of aqueous sodium chloride. The organic layer ^• is dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure to a residue. The residue is purified by column chromato- ' graphy to give 2-( 3-bromo-2, 3, 3-trifluoropropylthio)- thiazole.

(C) A stirred solution of 2.9 grams (0.01 mole) • of 2-(3-bromo-2,3, 3-trifluoropropylthio) thiazole and 1.5 grams (0.01 mole) of 1, 8-diazabicyclo[5.4.0]- undec-7-ene in 40 ml of toluene is heated under reflux for two hours. The solvent is removed by distillation and the residue is purified by column chromatography to give 1.1 grams of 2-( 2, 3, 3-trifluoro-2-propenyl- thio)thiazole. The appended Tables 1, la, lb and lc list compounds prepared as in the foregoing Examples. In

Tables la and lc the compounds are those of formula I

1 2 wherein Y , Y and Z are fluoro, based upon the use of 4-bromo-l, 1,2-trifluoro-1-butene as the starting material in the synthesis.

-25-

Pesticidal Use The compounds of the invention can be used against a variety of pests that attack plants and animals. In agriculture, they are useful as nemati- cides, particularly against plant-parasitic nematodes and "free-living" nematodes, i.e., nematodes not dependent on any specific plant or other host. An example of the latter is the microbivorous nematode Caenorhabditis elegans. This nematode will feed on bacteria such as Escherichia coli and is used as a screen for both agricultural and veterinary nemati- cides or anthelmintics.

When used as anthelmintics, in veterinary treat¬ ments for treatment of infestations of Ascaris lumbri- coides (roundworm in pigs) for example, the compounds may be administered orally, parenterally or topically either alone but more usually in a pharmaceutically acceptable carrier, to provide an appropriate dosage-. Such carriers include one or more of water, gelatine, sugars, starches, organic acids such as stearic or citric acid and salts thereof, talc, vegetable fats or oils, gums, glycols and other excipients, for admini¬ stration as solids (e.g., tablets or capsules) or liquids (e.g., solutions, suspensions or emulsions) . The compositions may also contain preservatives, stabilizers, wetting or emulsifying agents, buffers, salts and other therapeutic agents. The compositions may be formulated by conventional methods to contain about 5 to 95% by weight of the anthelmintic compound, preferably about 25 to 75% by weight. Further guidance to anthelmintic activity, formulations and modes of treatment, utilizing the compounds of the invention, is available from publications on the subject, such as the article "Chemotherapeutics, Anthelmintic" in Kirk-Othmer, Encyclopedia of Chemical

-26-

Technology, Third ed. , 5_ 451-468, and articles cited therein, and in the patent literature, such as U.S. Patent 3,576,892, col. 3, lines 29-56.

In using the compounds of the invention as agri- cultural nematicides, the compounds, like most agri¬ cultural chemicals, are generally not applied full strength, but are formulated with agriculturally acceptable carriers and various additives normally employed for facilitating the dispersion of active ingredients, optionally with other active ingredients, recognizing that the formulation and mode of applica¬ tion of a toxicant may affect the activity of the material. The present compounds may be applied, for example, as powders or liquids, the choice of applica- tion varying with the nematode species and environ¬ mental factors present at the particular locus of infestation. Thus, the compounds may be formulated as granules, dusts, wettable powders, emuϊsifiable con¬ centrates, solutions, suspensions, dispersions, con- trolled release compositions, and the like.

A typical formulation may vary widely in concen¬ tration of the active ingredient depending on the particular agent used, additives, carriers or other active ingredients used, the nematode species to be controlled, and the desired mode of application. With due consideration to these factors, the active ingre¬ dient of a typical formulation may, for example, suitably be present at a concentration of from about 0.5% up to about 99.5% by weight of the formulation. Surface active agents, if employed in the formulation, may be present at various concentrations, suitably in the range of 1 to 30% by weight.

Dusts are admixtures of the active ingredient with finely divided solid carriers and/or diluents such as talc, natural clays, kieselguhr, pyrophyllite,

-27-

chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulfur, lime, flours, and other organic and inorganic solid carriers. These finely divided formulations generally have an average particle size of less than about 50 microns (325 mesh, Standard U.S. Sieve Series). In most cases, the active ingredient will be present in dust formulations at a concentration in the range of 1 to 15%, and occasionally from 1% to about 30%, the balance of the composition typically comprising one or more agriculturally acceptable inerts as adjuvant, carrier, or diluent.

The nematicidal compounds of the invention may also be formulated as wettable powders. These formu- lations are in the form of finely divided particles which disperse readily in water or other liquid vehi¬ cles. The wettable powder is ultimately applied as a dry dust or a dispersion in water or other liquid. Typical carriers for wettable powders include fuller's earth, kaolin clays, silicas, and other highly absor¬ bent or adsorbent inorganic diluents. The concentra¬ tion of active ingredient in wettable powders is dependent upon physical properties of the active ingredient and the absorbency of the carriers. Liquids and low melting solids (mp less than 100°C) are suitably formulated in the concentration range of 5 to 50% by weight; usually 10 to 30%; high melting solids (mp greater than 100°C) being formulated in the range of 5 to 95% by weight, usually 50 to 85%. An agriculturally acceptable carrier or diluent, fre¬ quently including a small amount of a surfactant to facilitate wetting, dispersion and suspension, accounts for the balance of the formulation.

Miσroencapsulated or other controlled release

CT/US86/01284

-28-

formulations may also be used for application of compounds in accordance with this invention.

Emulsifiable concentrates (EC's) are homogeneous liquid compositions, usually containing the active 5 ingredient dissolved in a liquid carrier. Commonly used liquid carriers include xylene, heavy aromatic naphthas, isophorone, and other nonvolatile or slightly volatile organic solvents. For application of the nematicide, these concentrates are dispersed in 10 water, or other liquid vehicle, forming an emulsion, and are normally applied as a spray to the area to be treated. The concentration of the essential active ingredient in EC's may vary according to the manner in which the composition is to be applied, but, in 15 general, is in the range of 0.5 to 95%, frequently 10 to 80%, by weight of active ingredient, with the remaining 99.5% to 5% being surfactant and liquid, carrier.

Flowables are similar to EC's except that the 20 ingredient is suspended in a liquid carrier, generally water. Flowables, like EC's, may include a small amount of a surfactant, and contain active ingredient in the range of 0.5 to 95%, frequently from 10 to 50%, by weight of the composition. For application, flow- 25 ables may be _. diluted in water or other. liquid vehicle, and are normally applied as a spray to the area to be treated.

Typical wetting, dispersing or emulsifying agents used in these formulations include, but are not 0 limited to, the alkyl and alkylaryl sulfonates and sulfates and their sodium or calcium salts; alkylaryl polyether alcohols; sulfated higher alcohols; poly- ^• ethylene oxides; sulfonated animal and vegetable oils; sulfonated petroleum oils; fatty acid esters of poly- 5 hydric alcohols and the ethylene oxide addition

-29-

products of such esters; addition products of long- chain mercaptans and ethylene oxide; and addition products of alkylphenols such as nonylphenol and ethylene oxide. Many other types of useful surface- 5 active agents are available in commerce. The sur¬ face-active agent, when used, normally comprises from 1 to 15% by weight of the nematicidal composition;

Other useful formulations include simple solu¬ tions of the active ingredient in a relatively

10 non-volatile solvent such as corn oil, kerosene, propylene glycol, or other organic solvents. This type of formulation is particularly useful for ultra-low volume application.

The concentration of active ingredient in use

15 dilution is normally in the range of about 2% to about 0.1%. Many variations of spraying, dusting, and controlled or slow release compositions in the art may be used by ^' substituting or adding a compound of this invention to compositions known or apparent to the art.

20 The compositions may be formulated and applied with other suitable active ingredients, including other nematicides, insecticides, acaricides, fungi¬ cides, plant regulators, herbicides, fertilizers, etc. In applying the foregoing chemicals, an effective

25 nematode controlling amount of active ingredient must be applied, sometimes referred to herein as a "nemati¬ cidal amount." While the application rate will vary widely depending on the choice of compound, the formu¬ lation and mode of application, the plant species

2 being protected and the planting density, a suitable use rate may be in the range of 0.5 to 25 kg/hectare, preferably 1 to about 20 kg/hectare.

The compounds of this invention are usually applied by incorporating a formulation thereof into

35 the soil in which plants or agricultural crops are or

are to be planted, i.e., the locus of infestation. This may be achieved by incorporating the compounds into the soil or by broadcasting the formulation over the planted area or the area to be planted or by limiting the application to a small area or band in the root zone where plants are or are to be planted. It will be readily apparent where the latter method is employed that a nematicidal amount, that is, a nemati¬ cidal concentration in the soil, must be applied to the root zone. A suitable concentration for this purpose is in the range of 0.1 to about 50 parts by weight of compound of the invention per million parts of soil.

However, in a significant aspect of the inven- tion, it has been found that certain of the polyhalo¬ alkene derivatives of the invention have ^' efficacy against nematodes by foliar application, i.e., the ^• compounds are systemic nematicides. This aspect is exemplified hereinafter. The following are specific examples of formula¬ tions which may be utilized in accordance with the present invention. In these formulations the percen¬ tages are wt/wt.. 1. Typical dust formulation: Test Compound 5%

Base 95%

96% Attaclay 2% highly purified sodium lignosulfonate (100%) 2% powdered sodium lkylnapthalene sulfonate (75%)

- 31-

2. Typical emulsifiable concentrates:

(A) Test Compound 5.0%

Emulsifier A 4.0%

Emulsifier B 0.4% Emulsifier C 0.8%

Emulsifier D 1.3%

Refined xylene solvent 88.5%

Emulsifier A is the anionic calcium salt of dodecylbenzene sulfonate. Emulsifier B is a nonionic 6-molar ethylene oxide condensation product of nonyl- phenol. Emulsifier C is a nonionic 30-molar ethylene oxide condensation product of nonylphenol. Emulsifier D is a nonionic paste of 100% polyalkylene glycol ether. (B) Test compound 21.3%

Emulsifier A 4.2%

Emulsifier B 0.5%

Emulsifier C 0.9%

Emulsifier D 1.4% Refined xylene solvent 71.7%

(C) Test compound 5.0%

Emulsifier E 4.0%

Emulsifier F 3.0%

Emulsifier G 3.0% Dormant spray oil solvent

(non-volatile) 85.0%

Emulsifier E is an oil-soluble nonionic blend of polyoxyethylene ethers commercially available under the trademark and designation "T Mulz 808A" . Emulsi- fier F is a formulated nonionic concentrate commer¬ cially available under the trademark and designation "FloMo 200-4". Emulsifier G is the anionic free acid of a complex organic phosphate ester commercially available under the trademark and designation "Gafac RE-410".

-32-

3. Typical granule formulations:

(A) Test compound (technical) 5.0% Attapulgite carrier/diluent 95.0%

The carrier/diluent is a 20/40 or 60/90 mesh 5 hydrated aluminum magnesium silicate of low volatile matter having 2% free moisture.

(B) Test compound (technical) 5.0% Ground corn cobs, 14/40 mesh 95.0%

(C) Test compound (as emulsifiable 0 concentrate 2(B) above) 23.5%

Attapulgite carrier/diluent

[3(A) above] 76.5%

4. Typical solution formulation:

Test compound 0.3% 5 Acetone 55.9%

Water 43.8%

Biological Testing Compounds of this invention were tested as -follows for nematicidal and anthelmintic activity as dust o formulations (initial and residual activity) and as acetone/water formulations (systemic activity). The formulations are described above.

1. Initial Root-Knot Nematicidal Activity The activity against root-knot nematode 5 (Meloidogyne incognita) was determined by incorporat¬ ing the compound of the invention in nematode infested soil at rates in the range of 10 ppm to 0.078 ppm of compound. Several tomato or cucumber seedlings were planted in the nematode infested soil. Two weeks o after planting the test pots were evaluated to ascer¬ tain the degree of galling (swelling) on the roots of the plants, indicating the control provided by the test chemical.

The results expressed as percent control (deter- mined by knot index) are set forth as averages in

- 33-

Table 2 (appended). Knot index is a numerical desig¬ nation assigned at evaluation, having the following meanings:

Knot Index Observations 5 0 No swellings - complete control

1 75% less swellings than control plants

2 50% less swellings than control plants

3 25% less swellings than control plants

4 About same as control plants - 10 no control.

Percent control is related to knot index as follows:

Knot Index Percent Control 0 100

15 1 75

2 50

3 25

4 0

When the Knot Index is between 0 and 1 it is 20 further subdivided as follows to indicate how close the percent control is to 75% or 100%:

Knot Index Percent Control

0 . 8 80

0. 5 90

-5 0. 1-0.4 95-99

The results demonstrate that compounds of this invention are highly effective against root-knot nematodes at the application rates tested.

2. Residual Root-Knot Nematicidal Activity

30 The ability of nematicidal compounds of the invention to control root-knot nematode infestations in soil over a period of time after treatment was evaluated. Dust formulations of test compound (5%) were incorporated into soil samples at test compound 5 rates of 5 and 10 ppm. Subsequently, the treated soil

-34-

samples were inoculated with nematode inoculum at weekly intervals, and Knot Index and Percent Control determined on seedlings planted in the soil samples. Specifically, soil treated with test compound was 5 placed in 7.6 cm. diameter fiber pots and stored in a greenhouse. At one, two and four weeks post- reat¬ ment, the appropriate number of pots was infested with root-knot nematode eggs and larvae. A cucumber or tomato seedling was planted in each pot and evaluated τ_0 approximately two weeks after the soil infestation to obtain the test results reported in Tables 3 and 3a appended. The data shows that as compared with untreated, but nematode-inoculated control soil, planted with seedlings (which showed no nematode

15 control), substantial residual activity was exhibited with most of the test compounds at the application rates tested.

3. Stunt Nematode Test

The procedure was substantially the same as 0 in the initial root-knot nematode tests described above except that rates of application of formulated compound were 2.5 and 5 ppm in soil containing a corn seedling, with subsequent inoculation of the soil with combined larvae and adult stunt nematodes. The 5 samples were evaluated approximately four weeks after infestation. The results (Tables 4 and 4a appended) indicate good control at the test application rates as compared with untreated samples where no control was observed. "Percent control" means the difference 0 between average population counts between untreated and treated samples, divided by average population count of untreated sample, multiplied by 100.

4. Lesion Nematode Test

The procedure was substantially the same as 5 in the stunt nematode test described above except that

- 35-

pea seedlings were used. The results (Table 5 appended) show good control with many of the compounds at the application rates tested as compared with untreated samples (no control). "Percent Control" is 5 defined as follows:

Population Count Population Count in Check in Trtmt

Iwt of Roots Wt of Roots

I in Check Plant in Treated Plants 0 X 100

Population Count in Check Wt of Roots in Check Plant

5. Cyst Nematode Test

The procedure was substan ially the same as - described in the stunt nematode test except soybean seedlings were used. "Percent Control" (Table 6 appended) is as defined in the stunt nematode test results. The data indicate good control by most of the compounds at the application rates tested. 6. Soil Mobility

The ability of nematicidal compounds of the invention to move through nematode-infested soil and to control the nematodes was evaluated by incorporat¬ ing 5% dust formulations of test compound at 30 ppm rates into pots of root-knot nematode infested soil, and subsequently eluting the soil with 15 cm of water (equivalent to 15 cm of rainfall) into a series of two or more pots of untreated, but nematode-infested, soil. Specifically, the pots were 8 cm diameter

3 plastic pots containing a 10 cm layer of sand over a coarse grade filter paper disc. Sufficient soil was placed over the sand to fill the pots, and a second filter paper disc was placed over the soil. Each test compound-treated pot was nested over a series of two or more pots containing untreated, but nematode-

1284

-36-

infested soil, also containing sand filter paper discs as described for the treated soil pots. Fifteen cm of water was slowly dripped into the top pots and the pots were allowed to drain for 16-18 hours to remove excess water. The top filter of each pot was then removed and the pots were planted with a cucumber or tomato seedling. The seedlings were evaluated approximately two weeks after planting to give the test results reported in Tables 7 and 7a appended. The data indicate good soil mobility and nematicide control at the application rates tested as compared to untreated systems which showed no nematode control. "Knot Index" and "Percent Control" are as defined in the initial root-knot nematode tests above. 8. Systemic Activity

Compounds of the invention were tested for basipetal systemic activity against the root-knot

_ nematode. In this test, tomato plants are grown in 10.2 cm diameter fiber pots containing steam-pas- teurized soil mix (50% soil, 50% sand) until 4-6 true leaves appear. Three of the pots are then placed on a turntable in a spray hood and the plants sprayed with 50 ml of water/acetone solution containing the test compound. The soil surface is covered during the spraying to prevent spraying of the soil. After treatment, the potted plants are placed in a lighted drying chamber. The plants are then grown in a growth chamber at 25 ^β C for three days and inoculated with a standard nematode culture by incorporating the inoculum into the top cm of soil in the pots. The plants are returned to the growth chamber for about two weeks at which time the pots are allowed to dry until the plants begin to wilt. The roots are shaken free of soil and the degree of galling (swelling) noted as compared to galling of untreated control

plants. The results are expressed as Knot Index and Percent Control as defined in the initial root-knot nematode activity tests reported above in Table 2. Table 8 appended reports the test results. The data indicate that many of the compounds exhibited good systemic nematicidal activity at the application rates tested as compared with untreated plants wherein no nematicidal activity was evident. Systemic nema¬ ticidal activity of any substantial degree is highly unusual and desirable and is not available from any commercial nematicides.

9. C. Elegans Nematode Screening Test and Evaluation

This in-vitro test using the free-living nematode Caenorhabditis elegans, is a modification of the assay developed by Simpkin and Coles, J_^ Chem. Tech. Tiotechnol, 31:66-69 (1981). In this test, nematicidal activity is evaluated by placing a suspen¬ sion of C_^ elegans nematodes in a medium containing a food source (E^ coli) and a candidate nematicide at test rates of 5.0-0.156 ppm. One milliliter of a test medium consisting of 5 mg ampicillin, 10,000 units of mycostatin and 10 ml of a dense suspension of Escheri- chia coli per 100 ml of a buffer solution, was pipetted into each well of a 24-well microtiter plate. The candidate nematicide, suspended at the appropriate concentration in dimethylsulfoxide, was added to the wells in 2.5 1 volumes. Each rate of application was replicated two to three times. After thorough mixing of the contents of each well, 50 to 100 1 of a nematode suspension in a buffer was added so that each well received 10-15 nematodes. After the nematodes were added, the microtiter plates were incubated at 20°C for 5-6 days.

-38-

The effect of the candidate nematicide on the survival and the reproduction of C^ elegans was then evaluated by comparison of the level of population developed in the treated wells with that in untreated wells. Specific effects on population development, such as reduced egg hatch or molting disruption, were noted if they were evident. Tables 9 and 10 appended show high activity test results for many compounds of the invention at the application rates tested.

3 9 - Table 1

F ₂ C-C-CH ₂ CH2X-R

Cmpd. No. Empirical Formula

C(0)CF CF ₂ CF3 C ₈ H ₄ F ₁₀ 0 ₂

4-chlorobenzoyl C]_]_H ₈ ClF3θ2

N =C-S C5H4F3NS

CH ₂ OH C5H7F3O

1155w30113Wjd-l

Table 1 (Continued)

Cmpd. No. X R Empirical Formula

N-

12 ^C 14 ^H 21 ^F 3 ^N 2S3

SC(CH ₃ ) ₂ CH ₂ C(CH ₃ ) ₃

N_ _N

14 C9H7F3N2S3

SCH ₂ C Ξ CH

1155W30113Wmd-2

- 41 - Table 1 (Continued)

Cmpd . No , X R Empirical Formula

18 -CH-CO-CH-CH-C = CF- _. 2. 2 21 2 ^c 10 10 ^F 6θ2S

19 0 -C(0)CF ₂ CF ₃ ^' (CH_CH ₂ ) ₂ 0 C ₁₁ H ₁₄ F ₈ 0 ₃

23 -C(0) C ₉ H ₁₀ F ₃ N0 ₂ S2

H55W30113Wmd-3

Table la

F

\

C C (CH ₂ ) ₂ S wherein: /

Compound Empirical Formula No. M.P. (°C)

25 -CH2CH2CF-C.F2 C ₁₀ H ₈ F ₆ N ₂ S3 liquid

26 4-nitrophenyImethyl C ₁₃ H _l0 F ₃ N ₃ O ₂ S ₃ liquid

R-

27 -SCH2CH2F C ₈ H ₈ F ₄ N ₂ S ₃ liquid

28 -SCH ₂ CH ₂ CSN C ₉ H ₈ F ₃ N ₃ S ₃ liquid

29 -SC3H7 C ₉ H ₁₁ F ₃ N ₂ S ₃ liquid

30 -SCH(CH ₃ ) ₂ C9H11F3N2S3 liquid

31 -SCH ₂ CH=CH ₂ C ₉ H ₉ F ₃ N ₂ S ₃ liquid

33 -SCH2Φ, 4-bromo C ₁₃ H ₁₀ BrF ₃ N ₂ S ₃ S (49-51)

H55W30113Wj d-4

- 43 -

Table 1a (Continued)

Compound Empirical Formula

No. R ³ M.P. (°C)

34 -SCH ₂ (j>, 2-fluoro ^C 13 ^H 10 ^F 4N2S3 liquid

35 -SCH ₂ φ, 4-nitro ^C 13 ^H 10 ^F 3N3°2S3 1iquid

36 2-thienylmethylt.ύo Ci 1H ^Q F3N S4 liquid

37 -(j),4-chloro C _L2 H ₈ C1F ₃ N ₂ S2 S (68-69)

38 -CH2Φ, 4-fluoro C13H10F4N2OS liquid

39 -φ, 4-chloro C ₁₂ H ₈ C1F ₃ N ₂ 0S S (49-52)

40 -(p, 4-nitro C ₁₂ H ₈ F ₃ N ₃ 03S S (61-64)

41 -C3H7 C9HHF3 2OS liquid

43 -CH ₂ ψ, 4-chloro ^C 13 ^H 10 ^C1F 3 ^N 2 ^OS liquid 1155W30113Wjd-5

- 4 ₄ - Table la (Continued)

Compound Empirical Formula No. R- M.P. CO

44 -CH ₂ , 2-fluoro -13H10F4N2OS liquid

45 -CH ₂ (j), 4-fluoro 13 ^H 10 ^F 4N2θS liquid

46 -CH ₂ (j), 2,4-difluoro C ₁₃ H ₉ F ₅ N ₂ OS liquid

47 -CH ₂ CH ₂ ⁽ j ^{) C} 14 ^H 13 ^F 3 ^N 2 ^0S liquid

48 -(j), 3-chloro C ₁₂ H ₈ C1F ₃ N ₂ 0S S (55)

49 - ), 4-bromo C ₁₂ H ₈ BrF ₃ N ₂ OS S (58-61)

50 -d), 4-fluoro C ₁₂ H ₈ F ₄ N ₂ OS

S (56-59)

1155w30113Wjd-6

Table lb

Cmpd. No. Name

1 2-( 3,4, 4-trif luoro-3-butenylthio) -4, 5- dihydrothiazole

2 2-methylthio-5-( 3, 4, 4-trif luoro-3-butenyl- thio)-l, 3,4-thiadiazole

3 ( 3, 4, 4-trif luoro-3-butenyl) heptaf luoro¬ butyrate

4 ( 3, 4, 4-trif luoro- 3-butenyl) 4-chlorobenzoate

5 _ ^" -( 3, 4, 4-trif luoro-3-butenyl)succinimide

6 (3, 4, 4-trif luoro-3-butenyl) isothiocyanate

7 4, 5, 5-trif luoro-4-penten-l-ol

8 3-chloro-5-(3,4,4-trifluoro-3-butenylthio)- 1,2,4-thiadiazole

9 3-broπ -5-(3,4,4-trifluoro-3-butenylthio)- 1,2,4-thiadiazole

10 2-(3,4,4-trifluoro-3-butenylthio)thiophene

11 2-(3,4,4-trifluoro-3-butenylthiomethy1)- thianaphthene

12 2-(1,1,3,3-tetramethylbutylthio)-5-(3,4,4- trifluoro-3-butenylthio)-l,3, -thiadiazole

13 2,5-di(3,4,4-trifluoro-3-butenylthio)-l,3,4- thiadiazole

14 2-propargylthio-5-(3,4,4-trifluoro-3- butenylthio)-!,3,4-thiadiazole

15 2-cyclopropylmethylthio-5-(3,4,4-trifluoro- 3-butenylthio)-l,3,4-thiadiazole

16 2-phenyl-5-(3,4,4-trifluoro-3-butenylthio)- 1,3,4-oxadiazole

17 2-(4--loropheι-yl)-5-(3,4,4-trifl-ioro-3- butenylthio)-1,3,4-oxadiazole

18 (3,4,4-trifluoro-3-buteπyl) (3,4,4-tri- fluoro-3-butenylthio)acetate

ll53W301l3Wjd-l

- 4 6 - Table lb (Continued)

C pd. No. Name

19 (3,4,4-trifluoro-3-butenyl) pentafluoro- prcpionate, mono diethyl etherate

20 (3,4,4-trifluoro-3-butenyl) 2-thiophene- carboxylate

21 (3,4,4-trifluoro-3-butenyl) 5-nitro-2- furancarboxylate .

22 (3,4,4-trifluoro-3-butenyl) 2-pyrrolecar- boxylate

23 (3,4,4-trifluoro-3-butenyl) [2-(4,5-di- hydrothiazolyl)thio]acetate

24 N-(3,4,4-trifluoro-3-butenyl)saccharine

25 3,5-di(3,4, -trifluoro-3-butenylthio)- 1,2,4-thiadiazole

26 3-(4-nitrophenylmethylthio)-5-(3,4,4-tri- fluoro-3-butenylthio)-1,2,4-thiadiazole

27 ^' 2-(2-fluoroethylthio)-5-(3,4,4-trifluoro-3- butenylthio)-l,3,4-thiadiazole

28 2-(2-cyanoethylthio)-5-(3,4,4-trifluoro-3- butenylthio)-1,3,4-thiadiazole

29 2-prcpylthio-5-(3,4,4-trifluoro-3-butenyl- thio)-1,3,4-thiadiazole

30 2-(1-methylethylthio)-5-(3,4,4-trifluoro-3- butenylthio)-1,3,4-thiadia ole

31 2-(2-propenylthio)-5-(3,4,4-trifluoro-3- butenylthio)-1,3,4-thiadiazole

32 2-phenylmethylthio-5-(3,4,4-trifluoro-3- butenylthio)-1,3,4-thiadiazole

33 2-(4-bromophenylmet- lthio)-5-(3,4,4-tri- fluoro-3-butenylthio)-1,3,4-thiadiazole

34 2-(2-fluorophenylmethylthio)-5-(3,4,4-tri- fluoro-3-butenylthio)-1,3,4-thiadiazole

H53W301l3ϊJjd-2

- 47 - Table lb (Continued)

Cmpd. No. Name

35 2-(4-nitrophenylmethylthio)-5-(3,4,4-tri- fluoro-3-butenylthio)-l,3,4-thiadiazole

36 2-(2-thienylmethylthio)-5-(3,4,4-trifluoro- 3-butenylthio)-l,3,4-thiadiazole

37 2-(4-chlorophenyl)-5-(3,4,4-trifluoro-3- butenylthio)-1,3,4-thiadiazole

38 3-(4-fluorophenylmethyl)-5-(3,4,4-trifluoro- 3-butenylthio)-1,2,4-oxadiazole

39 3-(4-chloropheπyl)-5-(3, ,4-trifluoro-3- butenylthio)-1,2,4-oxadiazole

40 3-(4-nitrophenyl)-5-(3,4,4-trifluoro-3- butenylthio)-l,2,4-oxadiazole

41 2-propyl-5-(3,4,4-trifluoro-3-butenylthio)- 1,3,4-ox ^' adiazole

42 2-pheπylmethyl-5-(3,4,4-trifluoro-.3-buteny1- thio)-1,3,4-oxadiazole

43 2-(4-chlorophenylmethyl)-5-(3,4,4-trifluoro- 3-butenylthio)-1,3,4-oxadiazole

44 2-(2-fluorophenylmethyl)-5-(3,4,4-trifluoro- 3-butenylthio)-1,3,4-oxadiazole

45 2-(4-fluorophenylmethyl)-5-(3,4,4-trifluoro- 3-butenylthio)-l,3,4-oxadiazole

46 2-(2, -difluorophenylmethyl)-5-(3,4,4-tri- fluoro-3-butenylthio)-1,3,4-oxadiazole

47 2-(2-pheπylethyl)-5-(3,4,4-trifluoro-3- butenylthio)-l,3,4-oxadiazole

48 2-(3-chlorophenyl)-5-(3,4,4-trifluoro-3- butenylthio)-l,3,4-oxadiazole

49 2-(4-bro ^~ opheπyl)-5-(3,4,4-trifluorc-3- butenylthio)-1,3,4-oxadiazole

50 2-(4-fluorophe ^~ yl)-5-(3,4,4-trifluoro-3- butenylthio)-1,3,4-oxadiazole ll53-v301l3VJjd-3

- 48 - Table lb ( Cont inued)

Cmpd. No. Name

230 2-( 3, 4, 4-trifluoro-3-butenylthio) hiazole

231 2-( 2, 3, 3-trifluoro-2-ρropenylthio) thiazole

232 2-(4, 4-difluoro-3-butenylthio) thiazole

233 2-(3,3-difluoro-2-propenylthio)thiazole

234 2-(4, 4-dichloro-3-butenylthio) thiazole

235 2-( 3, 3-dichloro-2-propenylthio) thiazole

236 2-(4, 4-dibromo-3-butenylthio) thiazole

237 2-(3, 3-dibromo-2-propenylthio)thiazole

238 2-(2, 3, 3-trichloro-2-proρenylthio) thiazole

239 2-( 3, 4, 4-trichloro-3-butenylthio) thiazole

240 2-(2, 3, 3-tribromo-2-propenylthio) thiazole

241 2-(3, 4, 4-tribromo-3-butenylthio)thiazole

1153W30113Wjd-4

- 49 -

Table lc

Substituted Thiadiazolyl/Oxadiazolyl Compounds

F F i

C = C(CH_)_SR wherein: / 2 2

Compound No. _____ M.P. (°C)

51 pheπylmethyl- liquid 52 4-chlorophenylmethyl- liquid 53 4-chloropheπylthiomethyl- liquid

54 R is liquid

55 R is liquid

1153w30113Wjd-25

- 50 - Table lc (Continued)

Compound No. M.P. ( ^β C)

56 4-chlorophenylmethyl- liquid 57 -SCH ₂ O_3 liquid 58 -SCH ₂ CF ₃ liquid 59 -SC ₄ H ₉ liquid 60 -SCH(CH ₃ )C ₂ H ₅ liquid 61 -SCH ₂ CH(CH ₃ ) ₂ liquid 62 -S(CH ₂ ) ₂ CClFCBrF ₂ liquid 63 -S(CH ₂ ) ₇ CH3 liquid 64 -S(CH ₂ ) ₁₀ CH3 liquid 65 -S(CH ₂ ) ₂ CH-CH ₂ liquid 66 -SCH(CH ₃ )CH-CH ₂ liquid 67 -SCH ₂ C(CH ₃ )-CH ₂ liquid 68 -SCH ₂ _H-CH(_H ₃ liquid 69 -S(CH ₂ ) ₃ CH-CH ₂ liquid

-SCH ₂ CH-C(CH ₃ ) ₂ liquid

71 -SCH ₂ C(C1) ^~ CH ₂ liquid 72 -SCH ₂ C(Br)=CH ₂ liquid 73 -SCH ₂ CH-C(Br) ₂ liquid 74 -S(CH ₂ ) ₂ CH-C(Cl)-0 solid (55°) 75 -SCH ₂ C≡N solid (69°) 76 -S(CH ₂ ) ₃ CSN liquid 77 -S(CH ₂ ) ₄ C^Ϊ liquid 78 liquid

79 2,4-di ethyl- liquid 80 3-_lorophenylmethylthio- liquid 81 4-^-hlorophenylmethylthio- solid (38°)

1153w30113Wjd-26

- 51 - Table lc (Continued

Compound No. _R 3 M.P. CO

82 3,4-dichlorophenylmethylthio- liquid

83 2,6-dichlorophenylmethylthio- liquid

84 2-bromophenylmethylthio- liquid

85 3-bro ^~ ophenylmethylthio- liquid

86 3,5—dibromophenyImethylthic— liquid

87 3-fluorophenylmethylthio- liquid

88 4-fluorophenylmethylthio- liquid

89 2,4-difluorophenylmethylthio- liquid

90 2,5-difluorσphenyImethylthio- liquid

91 3,4-difluoropheπylmethylthio- liquid

92 2,6-difluorcphenyImethylthio- liquid

93 2,3,4,5,6-pentafluorophenylmethylthio- liquid

94 2-chloro-6-fluorophenylmethylthio- liquid

95 2-iodophenylmethylthio- liquid

96 2-methyIphenylmethylthio- liquid

97 3-methyIphenylmethylthio- liquid

98 2-trif1uorometlψlphenyljnethylthio- liquid

99 S-trifluoromethylp.-snylmethylthio- liquid

100 4-trifluoromethyIphenyImethylthio- liquid

101 3-methoxyphenylιne hylthio- liquid

102 4-methoxyphenyImethylthio- solid (42-44°)

103 4-trifluoromethoxyphenylmethyl hio- liquid

104 2-cyanophenylmethylthio- liquid

105 3-cyanophenylmethyl hio- liquid

106 4-cyancphenyImethylthic— solid (51-57°)

107 2-nitrophenylmethylthio- liquid

108 3-nitrophenyImethylthio- liquid

109 2-chloro-4-nitrophenylmethylthio- liquid

110 4-chloro-2-nitrophenyImethylthic— liquid

111 2-fluoro-4-nitrophenylmethylthio- liquid

112 2-methyl-3-nitrophenyljtιethylthio- liquid

1153W30113Wjd-27

- 52 -

Table lc (Continued

Compound L No. R ³ M.P. (°C)

113 2-nitro-5-methyIphenyImethylthio— liquid

114 2-methoxy-5-nitrophenylmethylthio- liquid

115 3,5-dinitrophenyImethylthio- liquid

116 •4-phenyIphenylmethylthio- solid (62°)

117 2-methyl-3-phenyIphenylmethylthio- solid

118 anthracine-9-ylmethylthio- liquid

119 5-chlorothien-2-ylmethylthio- liquid

120 2-methylthiazol-4-ylme hylthio- liquid

121 2,6-dichloropyridin-4-yImethyIthio- liquid

122 1,3-be ^~~ odioxol-5-yl_nethylthio- liquid

123 phenylthiomethylthic— liquid

124 1-phenylethylthio- liquid

125 2-(4-nitropheny1)ethylthio- liquid

126 3-ρhenoxypropylthio- liquid

127 -N[C(0)CF ₃ ][C ₂ H ₅ ] liquid

128 - [C(0)CH ₃ ][CH3] liquid

129 -N[C(0)CH ₃ ][4-trifluoromethylphenyl] solid

130 1,2-bis(4-chloroρheny1)urea- solid

131 -N[C(0)CF ₃ ][4-methoxypheπyl] solid

132 4-trifluoromethyIphenylamino- solid

133 4-methoxyphenylamino- solid

134 4-chiorophenylamino- lζ ^C V ^CH ₃ solid

135 -N[C(0) CH-CC1 ₂ ][CH ₃ ] liquid

136 1-(4-trifl-orάnethylpheiy1)-2-(4- solid chloropheny1)urea-

137 l-methyl-2-(4-chloropheπyl)urea- solid (141-2°)

1153W30113Wjd-28

- 53 - Table lc (Continued)

Compound No. _R3_ M.P. (°C)

138 -N[C(0)CH ₃ ][4-chlorophenyl] solid (84-85°) 139 -N[C(0)CH ₃ [4-fluorophenyl] solid (96-97°)

140 liquid phenyl]

141 4-nitrophenylamino- solid 142 l-ethyl-2-(4-chlorophenyl)urea- solid 143 -N[C(0)CH.][4-methoxypheny1] solid 144 1-(4-fluorophenyl)-2-(4-chlorophenyl)- solid urea

145 -NHC ₂ H ₅ solid 146 4-fluorophenylamino- solid 147 -N[CH-,][2,4-dichlorophenylmethyl- liquid carboπyl]

148 liquid

149 4-bromopheπylamino- solid

150 liquid methylphenyl]

151 -N C ₂ H ₅ ][phenylmethoxycarbonyl] solid 152 -^0(0)0^][C ₂ H ₅ ] liquid 153 bromαmethylthic— liquid 154 -N[C(0)CH ₃ ][4-bromophenyl] solid

1153W301l3Wmd-29

- 5 4 - Table lc (Continued)

Compound No. R3 M.P. CO

155 solid

156 liquid

157 -s(α_ ₂ ) ₃ α_ ₂ cι semi-solid

158 -SCH-.C1 liquid

159 -S(CH ₂ ) ₄ C1 lqiuid

160 -S(CH ₂ ) ₂ CH ₂ C1 liquid

161 -S(CH ₂ ) ₃ CH ₂ Br solid (67-69°)

Compound No. R4 M.P. CO

162 4-chlorophenylmethyl' liquid

163 4-methylpheπyl- liquid

164 phenylmethyl- liquid

165 phenyl- liquid

166 2-chlorophenyl- liαuid

1153w30113Wjd-30

Compound No. _R 4 M.P. ( °C)

167 3-chlorophenyl- solid (48-51°)

168 3-trifluoromethylphenyl- solid (41-44°)

169 4-methoxyphenyImethy1- liquid

170 3-nitrcpheny1- solid (69-71°)

Coπpound No. M.P. CO

171 -α_ ₃ liquid 172 -C ₂ H ₅ liquid 173 -CH(CH ₃ ) ₂ liquid 174 -CH ₂ CH(CH ₃ ) ₂ liquid 175 -C(CH ₃ ) ₃ liquid 176 -(CH ₂ ) ₄ CH ₃ liquid 177 solid (45°) 178 -<_≡C(CH ₂ ) ₄ CH ₃ liquid 179 -CH CH(CH ₃ )CF ₃ liquid 180 2-chlorophenylmethyl- liquid 181 2-bromophenyImethy1- liquid 182 4-broιtDpheny lme thy 1- solid (38-40°) 183 2-methyIphenyImethy1- liquid 184 3-methyIphen lmethyl- liquid 185 2-bromo-4,5-dimethoxyphenyImethy1- solid (54-59°) 186 2-nitrophen lme hyl- liquid 187 4-nitrophenyImethy1- liquid 188 thien-2-ylmethyl- liquid 189 1,4-benzodioxan-6-yImethy1- liquid

1153W30113Wjd-31

- 56 -

Table lc (Continued)

Compound No. ___ ⁵ _ .P. CO

190 1,3-benzodioxol-5-ylmethyl- solid (69-71°)

191 liquid

192 l-p eny et y - liquid

193 2-(4-nitropheny1)ethyl- liquid

194 2-(4-chlorophenyl)ethenyl- liquid

195 2-(4-bromophenyl)ethenyl- liquid

196 2-(2-fluorophenyl)ethenyl- liquid

197 3-phenylpropyl- liquid

198 4-phenylbutyl- liquid

199 4-chloroρhenoxymethyl- liquid

200 4-methylphenoxymethyl- liquid

201 3-methyl-4-chlorophenoxymethyl- liquid

202 4-nitrophenoxymethyl- liquid

203 1-(4-chlorophenoxy)ethyl- liquid

204 1-(4-methylphenoxy)ethyl- liquid -

205 2-(4-chlorophenylthio)ethyl- solid (54-59°)

206 1-(4-chlorophenoxy)propyl- liquid

207 2-chlorophenyl- liquid

208 2-bromophenyl- liquid

209 2,5-dichloropheπyl- liquid

210 4-(1-methylethyl)phenyl- liquid

211 2-methoxypheπyl- liquid

212 3-methoxyphenyl- liquid

213 4-methoxyphenyl- liquid

214 3,4-dimethoxyphenyl- solid (51°)

215 4-nitrqpheπyl- solid (94-96°)

216 2-aminopherιyl- solid (57-61°)

217 4-hydroxypheπyl- solid (96-101°)

1153W30113Wmd-32

Table lc (Continued)

Compound No. _R5_ M.P. (°C)

218 4-acetyloxyphenyl- solid (63-66°)

219 4-(methylaminocarbonyloxy)phenyl- solid (108-111°)

220 4-phen lpheny1- solid (49-52°)

221 naphth-2-yl- solid (70-72°)

222 naphth-1-yl- solid (68°)

223 thien-2-yl- liquid

224 furan-2-yl- liquid

225 4-methyl-l, 2,3-thiadiazol- -5-yl- liquid

226 2-(4-chloropheny1)ethy1- solid (43-45°)

227 2-(2-chlorophenyl)ethyl- liquid

228 2-(4- luorophenyl)ethy1- liquid

229 phenylmethyl liquid

H53W301l3Wjd-33

- 58 - Table Id ( Cont inued )

Polyhaloalkenylthio Thiazolyl Compounds

Compound No. n M.P. CO

230 2 liquid 231 1 liquid

1153W30113Wjd-36

Table 2

Initial Activity Against the Root-knot Nematode

.Application Percent

Compound No. Rate (ppm) Control

1 10.0 100

5.0 99

2.5 99

5.0 100

2.5 100

1.25 99

0.625 100

0.313 99

0.625 100

0.313 98

0.156 95

0.078 56

2 10.0 100

5.0 96

2.5 96

• 5.0 99

2.5 95

1.25 86

0.625 84

0.313 38

3 10.0 95

5.0 83

2.5 71

4 2.5 99

1.25 56

0.625 44

0.313 38

5 2.5 81

1.25 70

0.625 6

0.313 0

6 10.0 100

5.0 78

- 2.5 38

7 10.0 79

5.0 44

2.5 25

1153W30113Wjd-4

Table 2 (Continued)

Application Percent

Compound No. Rate (ppm) Control

8 2.5 100 1.25 100 0.625 100 0.312 100

0.625 100 0.312 98 0.156 95 0.078 58

10 5.0 99 2.5 95 1.25 81 0.625 63

11 5.0 83 2.5 78 1.25 67 0.625 0

12 2.5 100 1.25 79 0.625 69 0.313 8

13 2.5 99

1.25 99

0.625 96

0.313 71

0.625 95 0.313 79 0.156 13 0.078 0

14 2.5 83 1.25 25 0.625 0 0.313 0

15 2.5 100 1.25 97 0.625 31 0.313 6

1153W30113Wjd-5

Table 2 (Continued)

Application Percent

Compound No. Rate (ppm) Control

16 2.5 95

1.25 44

0.625 25

0.313 0

17 10.0 100

5.0 100

2.5 100

18 10.0 100

5.0 99

2.5 96

5.0 80

2.5 69

1.25 38

0.625 19

0.313 0

19 10.0 69

5.0 75

2.5 58

20 2.5 98

1.25 63

0.625 6

0.313 0

21 2.5 64

1.25 31

0.625 8

0.313 0

22 2.5 96

1.25 44

0.625 0

0.313 0

23 10.0 96

5.0 84

2.5 76

24 10.0 78

5.0 63

2.5 19

1153w30113Wjd-6

- 62 -

Table 2 (Continued)

Application Percent

Compound No. Rate (ppm) Control 25 2.5 99

1.25 97

.625 97

.312 78

26 2.5 86

1.25 63

.625 0

.312 0

27 2.5 100

1.25 99

.625 79

.312 31

28 2.5 100

1.25 98

.625 86

.312 81

29 2.5 99.

1.25 99

.625 99

.312 95

30 2.5 100

1.25 99

.625 99

.312 97

31 2.5 99

1.25 96

.625 78

.312 69

.625 63

.312 44

.156 13

.078 0

32 2.5 100

1.25 99

.625 97

.312 78

1153W30113Wjd-7

- 63 -

Table 2 (Continued)

Application Percent

Compound No. . Rate (ppm) Control 32 cont'd .625 98

.312 69

.156 31

.078 8

33 2.5 97

1.25 84

.625 70

.312 38

34 2.5 100

1.25 99

.625 99

.312 86

.625 99

.312 86

.156 64

.078 38

35 2.5 100

1.25 ^' 98

.625 70

.312 67

.625 97

.312 51

.156 6

.078 0

35 2.5 100

1.25 99

.625 96

.312 69

.625 99

.312 71

.156 25

.078 0

37 .625 0

.312 0

.156 0

.078 0

1153W30113Wjd-8

Table 2 (Continued)

Application Percent

Compound No. Rate (ppm) Control

38 2.5 98 1.25 96 .625 76 .312 63

39 2.5 100 1.25 98 .625 84 .312 19

2.5 100 1.25 99 .625 83 .312 19

40 2.5 99 1.25 84 .625 56 .312 0

41 2.5 100 1.25 100 .625 ^• 98 .312 76

.625 100 .312 97 .156 84 .078 31

42 2.5 100 1.25 98 .625 98 .312 86

.625 96 .312 83 .156 50 .078 38

43 .625 99 .312 78 .156 38 .078 13

H53W30113Wjd-9

- 65 -'

Table 2 (Continued)

Application Percent

Compound No. Rate (ppm) Control

43 cont'd .5 99

2.5 97

1.25 56

.625 13

44 2.5 98

1.25 86

.625 76

.312 50

45 2.5 99

1.25 99

.625 99

.312 95

46 2.5 99

1.25 98

.625 98

.312 85

47 2.5 100

1.25 96

.625 95

.312 95

48 2.5 98

1.25 95

.625 78

.312 64

.625 87

.312 56

.156 38

.078 6

49 2.5 100

1.25 100

.625 100

.312 98

50 2.5 100

1.25 99

.625 99

.312 78

H53W30113Wjd-10

• - 66 -

Table 2 (Continued)

Application Percent

Compound No. Rate (ppm) Control

230 2.5 100 1.25 100 0.625 81 0.313 44

H53W30113Wjd-12

Table 3

Residual Activity Against the Root-knot Nematode

Inoculation, Q ^~ pd. Application Weeks After Percent No. Rate (ppm) Treatment Control

1 10 1 98

2 44

4 0 10 1 99

2 75

4 42

1 99

2 63

4 25

10 1 77

2 56

4 69

10 1 96

2 38

4 50

1 98

2 38

4 42

8 1 _

2 -

4 98

13 10 1 99

2 99

4 95

1 98

2 98

4 75

18 10 1 0

2 0

4 0

21 1 13

2 8

4 0

1153W30113Wjd-ll

Table 3a

Residual Activity Against The Root-Knot Nematode - 5% Dust - Application Rate: 5 ppm

Inoculation Percent

■Compound No. Post-Treatment Control

25 1 Week 100

2 Weeks 97

4 Weeks 98

27 1 Week 99

2 Weeks 97

4 Weeks 99

28 1 Week 100

2 Weeks 100

4 Weeks 8

29 1 Week 100

2 Weeks 98

4 Weeks 81

30 1 Week 98

, 2 Weeks 97

4 Weeks 83

31 1 Week 97

2 Weeks 97

4 Weeks 95

32 1 Week 99

2 Weeks 99

4 Weeks 82

1 Week 99

2 Weeks 99

4 Weeks 98

35 1 Week 99

2 Weeks 96

4 Weeks 84

36 1 Week 98

2 Weeks 99

4 Weeks 95

53W30113Wjd-12

Table 3a (Continued)

Inoculation Percent

Compound No. Post-Treatment Control

41 1 Week 97

2 Weeks 63 4 Weeks 6

42 1 Week 99

2 Weeks 97 4 Weeks 0

43 1 Week 100

2 Weeks 100 4 Weeks 100

44 1 Week 100

2 Weeks 100 4 Weeks 100

45 1 Week 99

2 Weeks 100 4 Weeks 98

46 1 Week 99

2 Weeks 100 4 Weeks 99

47 1 Week 96

2 Weeks 25 4 Weeks ^■ 0

48 1 Week 97

2 Weeks 97 4 Weeks 69

1153W30113Wjd-13

Table 4

Initial Activity Against the Stunt Nematode

Rate of Percent Compound. No. Application (ppm) Control

1 10 61

5 30

2 5 72

6 5 51

0113Wjd-14

- 71 -

Table 4a

Initial Activity Against the Stunt Nematode Application rate: 5 ppm

*Some phytotoxicity

ll53W301l3Wjd-15

Table 5

Initial Activity Against the Lesion Nematode

Rate of Percent

Application (ppm) Control

5 82

5 52

2.5 0

2 5 0 10 2.5 33 18 5 0 21 2.5 54 25 2.5 77

2.5 79

27 2.5 63 28 2.5 45 29 2.5 68 30 2.5 75 31 2.5 11 32 2.5 28

2.5 15

1.25 0

.625 0

33 2.5 46 34 2.5 52

2.5 58

2.5 55

35 2.5 52

2.5 78

1153W30113Wjd-16

Table 5 (Continued)

Rate of Percent

Compound No. Application- (ppm) Control

36 2.5 59

2.5 19 1.25 2 .625 0

2.5 71

41 2.5 64

42 2.5 73 82

43 2.5 93

2.5 78

44 2.5 88

45 2.5 41

46 2.5 77

47 2.5 69

48 2.5 85

2.5 78

ll53W30113Wjd-17

Table 6

Initial Activity Against the Cyst Nematode

Rate of Percent

Compound No. Application (ppm) Control

1 5 94

5 79l

2 5 70

8 5 92

18 5 8

21 2.5 33

25 5 83

27 5 57

31 5 7

32 5 ^' 16

5 78

35 5 0

36 5 37

41 5 0

42 5 30

44 5 59

48 5 86

Iwhole cysts rather than homogenized cysts were used.

ll53W30113Wjd-18

Table 7

Soil Mobility Evaluations Against the Root- -knot Nemat

Location

Application of Test Percent Cmpd. No. Rate (ppm) Container Control

1 30 Top 97

Middle 95

Bottom 85

10 1 (TOD) 100

2 100

3 100

4 99

5 97

6 (Bottom) 42

5 Top 100

Middle 98

Bottom 99

2.5 Top 100

Middle 100

Bottom 100

1.25 Top 100

Middle 99

Bottom 96

0.625 Top 97

Middle 98

Bottom 77

0.313 Top 77

Middle 75

Bottom 25

2 30 Top 42

Middle 33

Bottom 25

8 5 Top 100

Middle 100

Bottom 96

18 30 Top 33

Middle 25

Bottom 25

21 30 Top 100

Middle 96

Bottom 99

1153W30113Wjd-19

84

- 7 ₆ -

Table 7a

Soil Mobility Evaluations Against The Root-Knot Nematode - 5% Dust; Application Rate: 5 ppm

Location of Percent

Compound No. Test Container Control

25 TOP 100

MIDDLE 69

BOTTOM 8

27 TOP 99 MIDDLE 100

BOΠΌM 100

28 TΌP 68

MIDDLE 83 BOTTOM 68

29 TOP 98 MIDDLE 81

BOTΓOM 50

30 TOP 99

MIDDLE 100

BOTTOM 17

31 TOP 98

MIDDLE 86

BOTTOM 50

32 TOP 99

MIDDLE 75

BOTTOM 25

34 TOP 98

MIDDLE 67

BOTTOM 8

35 TOP 99

MIDDLE 50

BOTTOM 0

36 TOP 97

MIDDLE 17

BOTTOM 0

38 TOP 0 MIDDLE 0

BOTTOM 0

53W30113Wjd-20

- 77 -

Table 7a (Continued)

Location of Percent

Compound No. Test Container Control

41 TOP 97*

MIDDLE 95*

EXDTΓOM 8

42 TOP 100

MIDDLE 100

BC-TOM 100

43 OP 99

MIDDLE 97

BOTTOM 81

44 TOP 100

MIDDLE 100

BOTTOM 96

45 TOP 98

MIDDLE 97

BOTTOM 83

46 TOP 96

MIDDLE 97

BOTTOM 78

47 TOP - 98

MIDDLE 96

EJOTTOM 58

48 TOP 50

MIDDLE 0

BOTTOM 0

TOP 96*

MIDDLE 75

BOTTOM 42

49 TOP 99

MIDDLE 71

BOTTOM 8

50 TOP 98

MIDDLE 71

BOTTOM 33

*Some phytotoxicity

53w30113Wjd-21

4

— 78 "

Table 8

Systemic Activity Against the Root-knot : Nematodes

Application Test Percent

Cmpd. No. Rate (ppm) Control

12 2000 73, 99 1000 42, 95

13 2000 79

15 2000 83

16 2000 67

17 2000 42

31 2000 71 1250 0

32 2000 25

33 2500 17

.35 2000 0

36 2000 97 1250 17

41 2000 17

48 2000 50 2500 33

1153W30113Wjd-22

- 7 9 - Table 10

Evaluations Against C. Elegans

Percent

Rate Inhibition of Percent

Compound No. (PPM) Reproduction Mortality

25 5 100 100

2.5 58 0

1.25 17 0

26 5 100 100

2.5 100 100

1.25 100 100

32 5 100 8

2.5 42 0

1.25 25 0

33 5 100 100

2.5 100 100

1.25 100 100

34 5 - 100 100

2.5 100 100

1.25 0 0

35 5 100 100

2.5 100 100

1.25 100 100

37 5 100 100

2.5 100 100

1.25 100 100

39 5 100 100

5 100 100

2.5 100 100

2.5 100 100

1.25 100 67

1.25 100 58

40 5 100 100

2.5 100 100

1.25 100 100

43 5 100 83

2.5 100 67

1.25 42 0

48 5 100 100

2.5 25 0

1.25 17 0

H53W30113Wjd-24

- 80 - Table 9

Screen Against C. Elegans - Rate: 5 ppm

Percent

Inhibition of Percent

Compound No. Reproduction Mortality

25 100 75

26 100 100

27 38 0

31 38 0

32 100 100

33 100 100

34 100 25

35 100 100

37 100 100

39 100 100

43 100 25

44 25 0

45 25 0

48 100 88

H53W301l3Wjd-23