KR20050018941A - Cyano anthranilamide insecticides - Google Patents

Abstract

The present invention provides compounds of formula I, N-oxides and suitable salts thereof.

<Formula I>

Wherein R ¹ is Me, Cl, Br or F; R ² is F, Cl, Br, C ₁ -C ₄ haloalkyl or C ₁ -C ₄ haloalkoxy; R ³ is F, Cl or Br and; R ⁴ is H or each halogen, CN, SMe, S (O ) Me, S (O) 2 Me, and optionally with one substituent selected from the group consisting of OMe-substituted C ₁ -C ₄ alkyl, C ₃ -C ₄ alkenyl, C ₃ -C ₄ alkynyl, C ₃ -C ₅ cycloalkyl, or C ₄ -C ₆ cycloalkylalkyl; R ⁵ is H or Me; R ⁶ is H, F or Cl R ⁷ is H, F or Cl. Also for controlling invertebrate pests comprising contacting the invertebrate pest or environment thereof with a biologically effective amount of a compound of formula (I), an N-oxide thereof, or an appropriate salt of the compound (eg, as a composition described herein) The method is disclosed. The invention also provides for the control of invertebrate pests comprising a biologically effective amount of a compound of formula (I), an N-oxide thereof, or a suitable salt of the compound and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. It relates to a composition for the following.

Description

Cyano anthranylamide insecticide {CYANO ANTHRANILAMIDE INSECTICIDES}

The present invention provides certain anthranilamides, N-oxides, salts and compositions thereof suitable for agricultural and non-agricultural uses, including those listed below, and methods of using the same to control invertebrate pests in both agricultural and non-agronomic environments. It is about.

Control of invertebrate pests is very important in achieving high crop efficiency. Damage to invertebrate pests on agricultural crops in cultivation and in storage significantly reduces productivity and thereby increases costs to consumers. The control of invertebrate pests is also important in forests, greenhouse crops, ornamental plants, seedling crops, stored food and textile products, livestock, housekeeping, and public and animal health. Many products are commercially available for this purpose, but there is a continuing need for new compounds that are more effective, cheaper, less toxic, environmentally safer or have a different mode of action.

WO 01/070671 discloses N-acyl anthranilic acid derivatives of formula i as pesticides.

Wherein A and B are independently O or S; J is an optionally substituted phenyl ring, 5- or 6-membered heteroaromatic ring, naphthyl ring system or aromatic 8-, 9- or 10-membered fused heterobicyclic ring system; R ¹ and R ³ are independently H or optionally substituted C ₁ -C ₆ alkyl; R ² is H or C ₁ -C ₆ alkyl; Each R ⁴ is independently H, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, halogen or CN; n is 1-4.

Summary of the Invention

The present invention relates to compounds of formula 1, N-oxides or salts thereof.

Where

R ¹ is Me, Cl, Br or F;

R ² is F, Cl, Br, C ₁ -C ₄ haloalkyl or C ₁ -C ₄ haloalkoxy;

R ³ is F, Cl or Br;

R ⁴ is H; C ₁ -C ₄ alkyl, C ₃ -C ₄ alkenyl, C optionally substituted with one substituent selected from the group consisting of halogen, CN, SMe, S (O) Me, S (O) ₂ Me, and OMe, respectively ₃ -C ₄ alkynyl, C ₃ -C ₅ cycloalkyl, or C ₄ -C ₆ cycloalkylalkyl;

R ⁵ is H or Me;

R ⁶ is H, F or Cl;

R ⁷ is H, F or Cl.

The invention also relates to controlling an invertebrate pest comprising a biologically effective amount of a compound of Formula 1 and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent and optionally an effective amount of at least one additional biologically active compound or agent. It relates to a composition for.

The invention also relates to a method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of formula 1 (eg, as a composition described herein). The invention also relates to an invertebrate pest or environment thereof comprising a biologically effective amount of a compound of Formula 1 and one or more additional components selected from the group consisting of surfactants, solid diluents and liquid diluents, and optionally effective amounts of one or more additional biologically active compounds or agents A method of controlling an invertebrate pest comprising contacting a biologically effective amount of the composition further comprises.

The invention also relates to a spray composition comprising a compound of formula 1 and a propellant, and a bait composition comprising a compound of formula 1, one or more food substances, any attractant, and any humectant. The invention also includes a bait composition and a housing adapted to receive the bait composition, the mold having one or more openings of a size through which the invertebrate pest can pass through the opening. A device for controlling invertebrate pests that provides access to the bait composition from an external location and is further adapted to be located at or near a potential or known activity site of the invertebrate pest.

In the above description, the term "alkyl", alone or in compound words such as "alkylthio" or "haloalkyl", refers to a straight or branched chain alkyl such as methyl, ethyl, n-propyl, i-propyl or different. Butyl isomers. The term "halogen" alone or in compound words such as "haloalkoxy" includes fluorine, chlorine, bromine or iodine. In addition, when used in compound words such as "haloalkyl" or "haloalkoxy", the alkyl or alkoxy may be partially or completely substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" include F ₃ C, ClCH ₂ , CF ₃ CH ₂ and CF ₃ CCl ₂ . Examples of "haloalkoxy" include CF ₃ O, HCF ₂ O, CCl ₃ CH ₂ O, HCF ₂ CH ₂ CH ₂ O and CF ₃ CH ₂ O.

Those skilled in the art will understand that not all nitrogen-containing heterocycles can form N-oxides since nitrogen requires available lone pairs for oxidation to oxide. One skilled in the art will know nitrogen-containing heterocycles that can form N-oxides. Those skilled in the art will also recognize that tertiary amines can form N-oxides. Synthetic methods for the preparation of N-oxides of heterocycles and tertiary amines are well known to those skilled in the art and include peracetic acid and alkyl hydroperoxides such as m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, t-butyl hydroperoxide, sodium Perborate, and oxidation of heterocycles and tertiary amines with dioxiranes such as dimethyldioxirane. This method for the preparation of N-oxides has been extensively described and reviewed in the literature, for example in T. L. Gilchrist in Comprehensive Organic Synthesis, vol. 7, pp 748-750, S.V. Ley, Ed., Pergamon Press; M. Tisler and B. Stanovnik in Comprehensive Heterocyclic Chemistry, vol. 3, pp 18-20, A. J. Boulton and A. McKillop, Eds., Pergamon Press; M.R. Grimmett and B.R.T. Keene in Advances in Heterocyclic Chemistry, vol. 43, pp 149-161, A.R. Katritzky, Ed., Academic Press; M. Tisler and B. Stanovnik in Advances in Heterocyclic Chemistry, vol. 9, pp 285-291, A.R. Katritzky and A.J. Boulton, Eds., Academic Press; G.W.H. Cheeseman and E.S.G. Werstiuk in Advances in Heterocyclic Chemistry, vol. 22, pp 390-392, A.R. Katritzky and A.J. Boulton, Eds., Academic Press.

The compounds of the present invention may exist as one or more stereoisomers. Various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. Those skilled in the art will appreciate that one stereoisomer may be more active and / or may have a beneficial effect when concentrated or separated from other stereoisomer (s) as compared to other stereoisomer (s). One skilled in the art also knows how to isolate, concentrate and / or selectively prepare such stereoisomers. Accordingly, the present invention includes compounds selected from formula 1, their N-oxides and salts. The compounds of the present invention may exist in mixtures of stereoisomers, in individual stereoisomers or in optically active forms.

Salts of the compounds of the present invention are inorganic or organic acids, such as hydrobromic acid, hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, acetic acid, butyric acid, fumaric acid, lactic acid, maleic acid, malonic acid, oxalic acid, propionic acid, salicylic acid, tartaric acid, 4-toluene Acid-addition salts with sulfonic acids or valeric acid. In the compositions and methods of the present invention, salts of the compounds of the present invention are particularly suitable for the agricultural and / or non-agronomic uses described herein.

An important thing is

R ⁴ is H or C ₁ -C ₄ alkyl optionally substituted with one substituent selected from the group consisting of CN, SMe and OMe;

R ⁵ is H or Me;

R ⁶ is H;

Is a compound of Formula I wherein R ⁷ is H.

Preferred compounds for reasons of cost, ease of synthesis, and / or biological efficacy are as follows.

Preferred Compounds 1. R ¹ is Me or Cl; R ² is Cl, Br, CF ₃ , OCF ₂ H, OCF ₃ or OCH ₂ CF ₃ ; A compound of formula I, wherein R ⁴ is H, Me, Et, i-Pr, t-Bu, CH ₂ CN, CH (Me) CH ₂ SMe or C (Me) ₂ CH ₂ SMe.

Preferred compounds 2. R ² is Cl, Br, CF ₃ or OCH ₂ CF ₃ ; R ⁴ is H, Me, Et or i-Pr; Preferred compound of compound 1 wherein R ⁵ is H.

R ⁶ is H; Of note are preferred compounds 1 and 2, wherein R ⁷ is H.

Preferred compositions of the present invention include those preferred compounds. Preferred methods of use include those preferred compounds.

Compounds of Formula 1 may be prepared by one or more of the following methods and variations thereof as described in Schemes 1-20. The definitions of R ¹ , R ² , R ³ , R ⁴ , and R ⁵ in the compounds of Formula 1-24 are as defined in the Summary of the Invention unless stated otherwise.

The compound of formula 1 may be prepared by the reaction of benzoxazinone of formula 2 with an amine of formula HNR ⁴ R ⁵ as outlined in Scheme 1. This reaction can be carried out without solvent or in a variety of suitable solvents including tetrahydrofuran, diethyl ether, dioxane, toluene, dichloromethane or chloroform at room temperature to the reflux temperature of the solvent. The general reaction of benzoxazinones with amines to produce anthranylamides is well documented in the chemical literature. For a review of benzoxazinone chemistry, see Jakobsen et al., Biorganic and Medicinal Chemistry 2000, 8, 2095-2103 and references cited therein. See also GM Coppola, J. Heterocyclic Chemistry 1999, 36, 563-588.

Compounds of formula (1) can also be prepared from haloanthranilic diamides of formula (3), wherein X is halogen, preferably iodine or bromine, by the coupling method shown in Scheme 2. Acetonitrile, N, N-dimethylform, optionally in the presence or absence of suitable palladium catalysts (eg, tetrakis (triphenylphosphine) palladium (0) or dichlorobis (triphenylphosphine) palladium (II)) In a suitable solvent such as amide or N-methylpyrrolidinone, optionally at room temperature to the reflux temperature of the solvent, the metal cyanide (eg cuprous cyanide, zinc cyanide, or potassium cyanide) The compound is reacted to obtain the compound of formula 1. Suitable solvents when the palladium catalyst is used in the coupling reaction may be tetrahydrofuran or dioxane.

Cyanobenzoxazinone of Formula 2 may be prepared by the method outlined in Scheme 3. Halogenbenzoxazinones of formula (4) wherein X is halogen, preferably using a coupling method similar to that described in Scheme 2 above, optionally in the presence or absence of a palladium catalyst and optionally in the presence or absence of a metal halide. Iodide or bromine) and a metal cyanide to obtain a compound of formula 2.

The cyanobenzoxazinone of formula (2) may be prepared by the process detailed in Scheme 4 via coupling of pyrazole carboxylic acid of formula (5) with cyanoanthranilic acid of formula (6). The reaction was carried out by adding methanesulfonyl chloride to the pyrazole carboxylic acid of formula 5 in the presence of a tertiary amine such as triethylamine or pyridine followed by the addition of cyanoanthranilic acid of formula 6 followed by tertiary amine and methanesulphur Entails secondary addition of polyvinyl chloride.

Scheme 5 describes another method for preparing benzoxazinone of Formula 2 involving coupling of isatoic anhydride of Formula 7 with pyrazole acid chloride of Formula 8. Solvents such as pyridine or pyridine / acetonitrile are suitable for this reaction. Acid chlorides of formula 8 can be obtained from the corresponding acids of formula 5 by known methods such as chlorination with thionyl chloride or oxalyl chloride.

As shown in Scheme 6, the haloanthranilic diamides of formula (3) may be prepared by the same method as described for Scheme 1, with benzoxazinones of formula ( ⁴ ) wherein X is halogen and amines of formula HNR ⁴ R ⁵ It can manufacture by reaction of. The conditions for this reaction are similar to those specified in Scheme 1.

As shown in Scheme 7, the halogenbenoxoxazinone of Formula 4, wherein X is halogen, is reacted with the pyridylpyrazole carboxylic acid of Formula 5 and Formula 9 by the method analogous to that described above for Scheme 4. X may be prepared via direct coupling of haloanthranilic acid. This reaction is followed by addition of methanesulfonyl chloride to the pyrazolecarboxylic acid of formula 5 in the presence of a tertiary amine such as triethylamine or pyridine, followed by addition of haloanthranyl acid of formula 9, followed by tertiary amine and methane With secondary addition of sulfonyl chloride. In this way, benzoxazinone can generally be obtained in good yield.

As shown in Scheme 8, the halogenbenoxoxazinone of Formula 4 is coupled in a manner similar to that described above for Scheme 5, with isatoic anhydride of Formula 10 (where X is halogen) and pyrazole acid chloride of Formula 8 It can be prepared through.

Cyanoanthranilic acid of Formula 6 may be prepared from haloanthranilic acid of Formula 9 as outlined in Scheme 9. Haloanthranilic acid and cyanide of formula 9 (where X is halogen) using the same coupling procedure as described above for Scheme 2 (optionally with or without a palladium catalyst and optionally with or without metal halides) Compounds of formula (6) can be obtained by reaction of metals.

As shown in Scheme 10, the cyanoisatoic anhydride of formula 7 is either phosgene (or phosgene equivalent, such as triphosphene) or alkyl chloroformate (e.g., methyl chloroform) in a suitable solvent such as toluene or tetrahydrofuran. Mate) can be prepared from cyanoanthranilic acid of the formula (6).

As shown in Scheme 11, the haloanthranilic acid of Formula 9 is N-chlorosuccinimide (NCS), N-bromosuccinimide (NBS) or N-iodosuccinimide (NIS), respectively. It can be prepared by directly halogenating an unsubstituted anthranilic acid of Formula 11 in a solvent such as, N-dimethylformamide (DMF) to produce the corresponding halogen-substituted acid of Formula 9.

As shown in Scheme 12, the haloisatoic anhydride of formula 10 may be phosgene (or phosgene equivalent, such as triphosphene) or alkyl chloroformate, for example methyl chloroformate, in a suitable solvent such as toluene or tetrahydrofuran. It can be prepared from the haloanthranilic acid of the formula (9) by reaction with.

Pyridylpyrazole carboxylic acid of Formula 5 may be prepared by the method outlined in Scheme 13. 1-pyridylpyrazole (14) was reacted by reaction of 2-halopyridine of formula (13) with pyrazole (12) in the presence of a suitable base such as potassium carbonate in a solvent such as N, N-dimethylformamide or acetonitrile. Good specificity can be obtained with good specificity for the desired regiochemistry. The pyrazole carboxylic acid of formula 5 can be obtained by quenching the lithium salt with carbon dioxide after metallization of 14 with lithium diisopropylamide (LDA).

Starting pyrazole 12 (wherein R ² is CF ₃ , Cl or Br) is a known compound. Pyrazoles (12) in which R ² is CF ₃ are described in J. Chem. Fluorine Chem. 1991, 53 (1), 61-70. Pyrazoles (12), wherein R ² is Cl or Br, are also described in H. Reimlinger and A. Van Overstraeten, Chem. Ber. 1966, 99 (10), 3350-7]. A useful alternative method for the preparation of 12 in which R ² is Cl or Br is shown in Scheme 14. Metallization of sulfamoyl pyrazole (15) with n-butyllithium followed by anion with hexachloroethane (if R ² is Cl) or 1,2-dibromotetrachloroethane (if R ² is Br) Can be directly halogenated to obtain a halogenated derivative 16 (R ² is Cl or Br). Removal of the sulfamoyl group using trifluoroacetic acid (TFA) at room temperature proceeds in a completely good yield to yield pyrazoles 12, wherein R ² is Cl or Br, respectively.

As an alternative to the method shown in Scheme 13, pyrazolecarboxylic acids of Formula 5 wherein R ² is CF ₃ may also be prepared by the method outlined in Scheme 15. The cyclized product of formula 18 can be obtained after neutralization with an acid such as acetic acid by reaction of a suitable base with a compound of formula 17 (R ⁸ is C ₁ -C ₄ alkyl) in a suitable organic solvent.

Suitable bases are, for example, sodium hydride, potassium t-butoxide, dimsil sodium (CH ₃ S (O) CH ₂ -Na ⁺ ), alkyl metals (eg lithium, sodium or potassium) carbonates or hydroxides , Tetraalkyl (eg methyl, ethyl or butyl) ammonium fluoride or hydroxide, or 2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-dia It may be, but is not limited to, japosonin. Suitable organic solvents can be, for example, but not limited to acetone, acetonitrile, tetrahydrofuran, dichloromethane, dimethylsulfoxide, or N, N-dimethylformamide. The cyclization reaction is usually carried out at a temperature in the range of about 0 to 120 ° C. The effects of solvent, base, temperature and addition time are all independent and the choice of reaction conditions is important to minimize the formation of by-products. Preferred base is tetrabutylammonium fluoride.

Dehydration of the compound of formula 18 yields the compound of formula 19, after which the carboxylic acid is produced by hydrolysis of the carboxylic ester functional group to give the compound of formula 5. Dehydration is achieved by treatment with a suitable amount of acid in the catalytic amount. This catalytic acid can be, for example, but not limited to sulfuric acid. The reaction is generally carried out using an organic solvent. As will be appreciated by those skilled in the art, the dehydration reaction can be carried out in a variety of solvents, for example acetic acid, generally in the temperature range of about 0 to 200 ° C, more preferably about 0 to 100 ° C. Carboxylic acid esters of formula (19) can be converted to carboxylic acids of formula (5) by a number of methods, including hydrolysis methods involving nucleophilic cleavage or the use of acids or bases under anhydrous conditions. (TW Greene and PGM Wuts, Protective Groups in Organic Synthesis, 2nd ed., John Wiley & Sons, Inc., New York, 1991, pp. 224-269). For the method of Scheme 15, a hydrolysis method catalyzed with a base is preferred. Suitable bases include alkali metal (eg lithium, sodium or potassium) hydroxides. For example, the ester can be dissolved in a mixture of alcohol such as water and ethanol. Treatment with sodium or potassium hydroxide saponifies the ester to provide the sodium or potassium salt of carboxylic acid. Acidification with a strong acid such as hydrochloric or sulfuric acid yields a carboxylic acid of formula (5).

Compounds of formula 17 wherein R ² is CF ₃ can be prepared by the method outlined in Scheme 16. Treatment of the hydrazine compound of formula 20 with a ketone of formula CH ₃ COR ^{2 in} a solvent such as water, methanol or acetic acid yields a hydrazone of formula 21.

Those skilled in the art will understand that this reaction may require catalysis with any acid and an elevated temperature may also be required depending on the molecular substitution pattern of the hydrazone of formula 21. In the presence of an acid scavenger such as triethylamine in a suitable organic solvent (e.g., but not limited to dichloromethane or tetrahydrofuran), the reaction of Hydrazone of Formula 21 with alkyl chlorooxalate Compounds are provided. The reaction is usually carried out at a temperature of about 0 to 100 ° C. Hydrazine compounds of formula 20 may be prepared by standard methods, for example by reaction of the corresponding halopyridines of formula 13 with hydrazine.

As an alternative to the method shown in Scheme 13, pyrazolecarboxylic acids of Formula 5 wherein R ² is Cl or Br may be prepared by the method outlined in Scheme 17. Optionally, oxidation of the compound of formula 22 in the presence of an acid yields a compound of formula 19 wherein R ² is Cl or Br. Hydrolysis of a carboxylic ester functional group to a carboxylic acid provides a compound of formula (5).

The oxidizing agent for converting the compound of formula 22 to the compound of formula 19 is hydrogen peroxide, organic peroxide, potassium persulfate, sodium persulfate, ammonium persulfate, potassium monosulfate (e.g., oxone®) or potassium permanganate Can be. To attain complete conversion, at least one equivalent of oxidant should be used relative to the compound of formula 22, preferably about one to two equivalents. This oxidation is typically carried out in the presence of a solvent. The solvent may be an ether such as tetrahydrofuran, p-dioxane or the like, an organic ester such as ethyl acetate, dimethyl carbonate or the like, or a polar aprotic organic solvent such as N, N-dimethylformamide , Acetonitrile and the like. Acids suitable for use in the oxidation step include inorganic acids such as sulfuric acid, phosphoric acid and the like, and organic acids such as acetic acid, benzoic acid and the like. One to five equivalents of acid can be used. Preferred oxidants are potassium persulfate and oxidation is preferably carried out in the presence of sulfuric acid. The reaction can be carried out by mixing the compound of formula 22 in a preferred solvent and acid, if used. The oxidant can be added at a convenient rate. The reaction temperature is typically varied from about 0 ° C. up to below the boiling point of the solvent to obtain a suitable reaction time to complete the reaction. Suitable methods for converting the ester of formula 19 to the carboxylic acid of formula 5 are already described in Scheme 15.

Compounds of formula 22 wherein R ² is halogen and R ⁸ is C ₁ -C ₄ alkyl can be prepared from the corresponding compounds of formula 23 as shown in Scheme 18.

Treatment of the compound of formula 23 with a halogenating reagent, usually in the presence of a solvent, yields the corresponding halo compound of formula 22. Halogenation reagents that may be used include phosphorus oxyhalide, phosphorus trihalide, phosphorous pentahalide, thionyl chloride, dihalotrialkalphosphorane, dihalodiphenylphosphoran, oxalyl chloride and phosgene. Preferred are phosphorus oxyhalide and phosphorus pentahalide. To obtain complete conversion, at least 0.33 equivalents of phosphorus oxyhalide should be used relative to the compound of formula 23, preferably from about 0.33 to 1.2 equivalents. In order to obtain complete conversion, at least 0.20 equivalents of phosphorous pentahalide, preferably about 0.20 to 1.0 equivalents, relative to the compound of formula 23 should be used. Typical solvents for this halogenation are halogenated alkanes such as dichloromethane, chloroform, chlorobutane and the like, aromatic solvents such as benzene, xylene, chlorobenzene and the like, ethers such as tetrahydrofuran, p-dioxane Polar aprotic solvents such as acetonitrile, N, N-dimethylformamide and the like. Optionally, organic bases such as triethylamine, pyridine, N, N-dimethylaniline and the like can be added. Addition of a catalyst such as N, N-dimethylformamide is also optional. Preferred is a process wherein the solvent is acetonitrile and no base is used. Typically, no base or catalyst is required when acetonitrile solvent is used. A preferred process is carried out by mixing the compound of formula 23 in acetonitrile. The halogenation reagent is then added over a convenient time and the mixture is kept at the desired temperature until the reaction is complete. The reaction temperature is typically between 20 ° C. and the boiling point of acetonitrile and the reaction time is typically less than 2 hours. The reaction is then neutralized with an inorganic base such as sodium bicarbonate, sodium hydroxide or the like, or an organic base such as sodium acetate. Preferred products of formula 22 can be separated by methods known to those skilled in the art, including crystallization, extraction and distillation.

Alternatively, the compound of formula 22 wherein R ² is Br or Cl may be selected from the corresponding compound of formula 22 or p-toluenesulfo, wherein R ² is another halogen (eg, Cl to prepare formula 22 wherein R ² is Br) Sulfonate groups such as nate, benzenesulfonate and methanesulfonate can be prepared by treatment with hydrogen bromide or hydrogen chloride, respectively. In this way, the R ² halogen or sulfonate substituent on the compound of formula 22 is replaced with Br or Cl from hydrogen bromide or hydrogen chloride, respectively. The reaction is carried out in a suitable solvent such as dibromomethane, dichloromethane, acetic acid, ethyl acetate or acetonitrile. The reaction can be carried out at or near atmospheric pressure or at a pressure higher than atmospheric pressure in the pressure vessel. Halogenation reagents may be added to the reaction mixture containing the compound of formula 23 and a solvent in the form of a gas. When R ² in the starting compound of formula 22 is a halogen such as Cl, the reaction is preferably carried out in such a way as to remove the hydrogen halides produced in the reaction by sparging or other suitable means. Alternatively, the halogenating reagent is first dissolved in a highly soluble inert solvent (e. G. Acetic acid) and then the compound of formula 23 is contacted as is or in solution. The reaction can be carried out at about 0-100 ° C., most conveniently at ambient temperature (eg, about 10-40 ° C.), more preferably about 20-30 ° C. A Lewis acid catalyst (eg, aluminium tribromide to produce Formula 22 wherein R ² is Br) can be added to promote the reaction. The product of formula 22 is isolated by conventional methods known to those skilled in the art, including extraction, distillation and crystallization.

The starting compound of formula 22, wherein R ² is a sulfonate group, is selected from a suitable solvent such as dichloromethane with a base such as sulfonyl chloride (eg p-toluenesulfonyl chloride) and tertiary amine (eg triethylamine). It may be prepared from the corresponding compound of formula 23 by standard methods such as treatment.

As an alternative to the method shown in Scheme 13, pyrazolecarboxylic acids of Formula 5 wherein R ² is haloalkoxy can also be prepared by the method outlined in Scheme 19. The compound of formula 23 is oxidized to the compound of formula 24. The reaction conditions for this oxidation are as described for the conversion of the compound of formula 22 to the compound of formula 19 in Scheme 17.

The intermediate of formula 24 is then alkylated by reaction with a suitable haloalkylating agent such as haloalkyl halide or sulfonate to form a compound of formula 19 wherein R ² is haloalkoxy. The reaction is carried out in the presence of at least one equivalent of base. Suitable bases are inorganic bases such as alkali metal (eg lithium, sodium or potassium) carbonates, hydroxides and hydrides or organic bases such as triethylamine, diisopropylethylamine and 1,8 -Diazabicyclo [5.4.0] undec-7-ene. The reaction is generally alcohols such as methanol and ethanol, halogenated alkanes such as dichloromethane, aromatic solvents such as benzene, toluene and chlorobenzene, ethers such as tetrahydrofuran, and polarities such as acetonitrile, N, N-dimethylformamide And a solvent which may include an aprotic solvent and the like. Alcohols and polar aprotic solvents are preferred for use with inorganic bases. Preference is given to potassium carbonate as the base and N, N-dimethylformamide or acetonitrile as the solvent. The reaction is generally carried out between 0 and 150 ° C, most typically between ambient and 100 ° C. The ester of formula 24 may be converted to the carboxylic acid of formula 5 by the method already described for converting the compound of formula 19 to the compound of formula 5 in Scheme 15.

Compounds of formula 23 may be prepared from compounds of formula 20 as summarized in Scheme 20. In this method, the hydrazine compound of formula 20 is reacted with the compound of formula 25 in the presence of a base and a solvent (fumarate ester or maleate ester or mixtures thereof may be used).

Bases used in Scheme 20 are typically metal alkoxide salts such as sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, lithium tert-butoxide and the like. Polar protic and polar aprotic organic solvents such as alcohols, acetonitrile, tetrahydrofuran, N, N-dimethylformamide, dimethyl sulfoxide and the like can be used. Preferred solvents are alcohols such as methanol and ethanol. Particular preference is given if the alcohol is the same as making the fumarate or maleate ester and alkoxide base. The reaction is typically carried out by mixing the compound of formula 20 with a base in a solvent. The mixture may be heated or cooled to the desired temperature and the compound of formula 25 may be added over time. Typically the reaction temperature is between 0 ° C. and the boiling point of the solvent used. The reaction can be carried out under pressure above atmospheric pressure to raise the boiling point of the solvent. Temperatures of about 30 to 90 ° C. are generally preferred. The reaction can then be acidified by addition of an organic acid such as acetic acid or the like, or an inorganic acid such as hydrochloric acid, sulfuric acid or the like. Preferred products of formula 23 can be isolated by methods known to those skilled in the art, for example by crystallization, extraction or distillation.

It is recognized that some of the reagents and reaction conditions for preparing the compounds of Formula 1 may not be available for certain functional groups present in the intermediate. In this case, protection / deprotection sequences or functional interconversions will be added to the synthesis to help obtain the desired product. The use and selection of protecting groups will be apparent to those skilled in the art of chemical synthesis (see, eg, T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2nd ed .; Wiley: New York, 1991). Those skilled in the art will appreciate that in some cases it may be necessary to add a given reagent as described in each scheme, and then perform additional conventional synthetic steps that are not described in detail to complete the synthesis of the compound of Formula 1. Those skilled in the art will also recognize that it may be necessary to perform the combination of steps shown in the above schemes in an order other than that implied by the particular order provided for preparing the compound of Formula 1.

Without further elaboration, it is believed that one skilled in the art using the above description can use the present invention to its fullest extent. Thus, the following examples are merely illustrative and should be construed as not limiting the disclosure in any way. The steps in the examples below illustrate the process for each step in the overall synthetic transformation, and the starting material for each step does not necessarily have to be prepared by the particular manufacturing practice described in other examples or steps. Percentages are by weight except for chromatographic solvent mixtures or where otherwise stated. Parts and percentages for chromatography solvents are given in volume unless otherwise noted. ¹ H NMR spectra are reported in ppm shifted from tetramethylsilane to storage; "s" is singlet, "d" is doublet, "t" is triplet, "q" is quartet, "m" is multiline, "dd" is doublet of doublet, "dt" is doublet of triplet, "br s" means broad singlet.

Example 1

1- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6- (aminocarbonyl) phenyl] -3- (trifluoromethyl) -1H-pyrazole-5 Preparation of Carboxamides

Step A: Preparation of 2-Amino-3-methyl-5-iodobenzoic acid

To a solution of 2-amino-3-methylbenzoic acid (Aldrich, 5 g, 33 mmol) in N, N-dimethylformamide (30 mL) was added N-iodosuccinimide (7.8 g, 34.7 mmol), The reaction mixture was suspended overnight in a 75 ° C. oil bath. After removing the heat, the reaction mixture was slowly poured into ice water (100 mL) to precipitate a pale gray solid. The solid was filtered, washed four times with water and then placed in a vacuum oven at 70 ° C. to dry overnight. The desired intermediate was isolated as a light gray solid (8.8 g).

¹ H NMR (DMSO-d ₆ ): δ 7.86 (d, 1H), 7.44 (d, 1H), 2.08 (s, 3H).

Step B: Preparation of 3-chloro-2- [3- (trifluoromethyl) -1H-pyrazol-1-yl] pyridine

Potassium carbonate in a mixture of 2,3-dichloropyridine (99.0 g, 0.67 mol) and 3- (trifluoromethyl) -pyrazole (83 g, 0.61 mol) in anhydrous N, N-dimethylformamide (300 mL) (166.0 g, 1.2 mol) was added and the reaction heated to 110-125 ° C. over 48 hours. The reaction was cooled to 100 ° C. and filtered through a Celite® diatomaceous earth filtration aid to remove solids. N, N-dimethylformamide and excess dichloropyridine were removed by distillation at atmospheric pressure. Distillation of the product at reduced pressure (b.p. 139-141 ° C., 7 mm) afforded 113.4 g of the desired intermediate as a clear yellow oil.

¹ H NMR (CDCl ₃ ): δ 8.45 (d, 1H), 8.15 (s, 1H), 7.93 (d, 1H), 7.36 (t, 1H), 6.78 (s, 1H).

Step C: Preparation of 1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1H-pyrazole-5-carboxylic acid

3-chloro-2- [3- (trifluoromethyl) -1H-pyrazol-1-yl] pyridine in anhydrous tetrahydrofuran (700 mL) at −75 ° C. (ie pyrazole product from step B) To a solution of (105.0 g, 425 mmol) was added a -30 ° C solution of lithium diisopropylamide (425 mmol) in anhydrous tetrahydrofuran (300 mL) via cannula. After stirring the deep red solution for 15 minutes, carbon dioxide was blown at -63 ° C until the solution became pale yellow and the exotherm ceased. The reaction was further stirred for 20 minutes before stopping the reaction with water (20 mL). The solvent was removed under reduced pressure and the reaction mixture was partitioned between ether and 0.5 N aqueous sodium hydroxide solution. The aqueous extract was washed with ether (3 ×) and filtered through Celite® diatomaceous earth filter aid to remove residual solids, then acidified to about pH 4, at which time an orange oil formed. The aqueous mixture was stirred vigorously and additional acid was added to lower the pH to 2.5-3. The orange oil solidified into a granular solid, which was filtered, washed successively with water and 1N hydrochloric acid, and dried under vacuum at 50 ° C. to give 130 g of the title product as an off-white solid. The product obtained in a similarly processed run melted at 175-176 ° C.

¹ H NMR (DMSO-d ₆ ): δ 7.61 (s, 1 H), 7.76 (dd, 1 H), 8.31 (d, 1 H), 8.60 (d, 1 H).

Step D: 2- [1- (3-Chloro-2-pyridinyl) -3- (trifluoromethyl) -1H-pyrazol-5-yl] -6-iodo-8-methyl-4H-3 Of 1,1-benzoxazine-4-one

To a solution of methanesulfonyl chloride (2.91 mL, 37.74 mmol) in acetonitrile (50 mL) in 1- (3-chloro-2-pyridinyl) -3- (trifluoro in acetonitrile (50 mL) at -5 ° C Rhomethyl) -1H-pyrazole-5-carboxylic acid (ie, the carboxylic acid product of Step C) (10.0 g, 34.31 mmol) and triethylamine (4.78 mL, 34.31 mmol) were added dropwise. The reaction temperature was then maintained at 0 ° C. during the continuous addition of reagents. After stirring for 20 minutes, 2-amino-3-methyl-5-iodobenzoic acid (ie the product from Step A) (9.51 g, 34.31 mmol) was added and stirring continued for 10 minutes. Then, a solution of triethylamine (9.56 mL, 68.62 mmol) in acetonitrile (15 mL) was added dropwise, the reaction mixture was stirred for 30 minutes, and then methanesulfonyl chloride (2.91 mL, 37.74 mmol) was added. . The reaction mixture was allowed to warm to rt and stirred for 2 h. The solvent was evaporated under reduced pressure and the residual solid was purified by chromatography on silica gel to give 8.53 g of the title compound as a yellow solid.

¹ H NMR (CDCl ₃ ): δ 8.59 (dd, 1H), 8.35 (d, 1H), 7.97 (dd, 1H), 7.86 (d, 1H), 7.49 (m, 2H), 1.79 (s, 3H) .

Step E: 2- [1- (3-Chloro-2-pyridinyl) -3- (trifluoromethyl) -1H-pyrazol-5-yl] -6-cyano-8-methyl-4H-3 Of 1,1-benzoxazine-4-one

2- [1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1H-pyrazol-5-yl] -6-iodo-8- in tetrahydrofuran (10 mL) To a solution of methyl-4H-3,1-benzoxazin-4-one (ie, the benzoxazinone product of step D) (500 mg, 0.94 mmol), copper iodide (180 mg, 0.094 mmol), tetra Kis (triphenylphosphine) palladium (0) (5.4 mg, 0.047 mmol) and copper cyanide (I) (420 mg, 4.7 mmol) were added sequentially at room temperature. After heating the reaction mixture at reflux overnight, additional copper cyanide (I) (420 mg, 4.7 mmol), copper iodide (I) (107 mg, 0.56 mmol) and tetrakis (triphenylphosphine) palladium (0) (325 mg, 0.28 mmol) was added and refluxing continued for 1 hour. When the color of the reaction mixture turned black, thin layer chromatography on silica gel confirmed completion of the reaction. The reaction mixture was diluted with ethyl acetate (20 mL) and filtered through Celite®, washed three times with 10% aqueous sodium bicarbonate solution and once with brine. The organic extract was dried (MgSO ₄ ) and concentrated under reduced pressure to afford 410 mg of the title compound as a yellow crude solid.

¹ H NMR (CDCl ₃ ): δ 8.59 (dd, 1H), 8.33 (d, 1H), 8.03 (dd, 1H), 7.95 (d, 1H), 7.56 (m, 2H), 1.88 (s, 3H) .

Step F: 1- (3-Chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6- (aminocarbonyl) phenyl] -3- (trifluoromethyl) -1 H-pyra Preparation of Sol-5-Carboxamides

2- [1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1H-pyrazol-5-yl] -6-cyano-8- in tetrahydrofuran (5 mL) To a solution of methyl-4H-3,1-benzoxazin-4-one (ie, the cyanobenzoxazinone product of step E) (200 mg, 0.46 mmol) was added ammonium hydroxide (0.5 mL, 12.8 mmol) at room temperature. Added dropwise. The reaction mixture was then stirred for 5 minutes and thin layer chromatography on silica gel confirmed the completion of the reaction. The tetrahydrofuran solvent was evaporated under reduced pressure and the residual solid was purified by chromatography on silica gel to give 620 mg of the title compound, i.e. the compound of the present invention, as a solid which melts at 200-202 ° C.

¹ H NMR (CDCl ₃ ): δ 10.65 (s, 1H), 8.43 (dd, 1H), 7.9 (dd, 1H), 7.67 (s, 1H), 7.63 (s, 1H), 7.45 (m, 1H) , 7.25 (s, 1 H), 6.21 (bs, 1 H), 5.75 (bs, 1 H), 2.26 (s, 3 H).

Example 2

1- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6-[(methylamino) carbonyl] phenyl] -3- (trifluoromethyl) -1H-pyra Preparation of Sol-5-Carboxamides

Step A: 1- (3-Chloro-2-pyridinyl) -N- [4-iodo-2-methyl-6-[(methylamino) carbonyl] phenyl] -3- (trifluoromethyl)- Preparation of 1H-pyrazole-5-carboxamide

2- [1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1H-pyrazol-5-yl] -6-iodo-8- in tetrahydrofuran (15 mL) To a solution of methyl-4H-3,1-benzoxazin-4-one (ie, the benzoxazinone product of Example 1, step D) (500 mg, 0.94 mmol), methylamine (2.0 M solution in THF, 1.4 mL, 2.8 mmol) was added dropwise, the reaction mixture was stirred for 3 hours, and thin layer chromatography on silica gel confirmed the completion of the reaction. The tetrahydrofuran solvent was evaporated under reduced pressure and the residual solid was purified by chromatography on silica gel to give 400 mg of the title compound as a yellow solid.

¹ H NMR (CDCl ₃ ): δ 10.25 (s, 1H), 8.45 (dd, 1H), 7.85 (dd, 1H), 7.55 (s, 1H), 7.50 (s, 1H), 7.46 (s, 1H) , 7.40 (m, 1H), 6.15 (d, 1H), 2.93 (d, 3H), 2.12 (s, 3H).

Step B: 1- (3-Chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6-[(methylamino) carbonyl] phenyl] -3- (trifluoromethyl)- Preparation of 1H-pyrazole-5-carboxamide

1- (3-chloro-2-pyridinyl) -N- [4-iodo-2-methyl-6-[(methylamino) carbonyl] phenyl] -3- (tri in tetrahydrofuran (8 mL) In a solution of fluoromethyl) -1H-pyrazole-5-carboxamide (ie, the diamide product of Step A) (410 mg, 0.72 mmol), copper (I) iodide (24 mg, 0.126 mmol) at room temperature, Tetrakis (triphenylphosphine) palladium (0) (70 mg, 0.060 mmol) and copper cyanide (I) (640 mg, 7.2 mmol) were added sequentially. The reaction mixture was heated to reflux for 4.5 hours. Thin layer chromatography on silica gel confirmed the completion of the reaction. The reaction mixture was diluted with ethyl acetate (20 mL), filtered through Celite (R) and washed three times with 10% aqueous sodium bicarbonate solution and once with brine. The organic extract was dried (MgSO ₄ ) and concentrated under reduced pressure and the residual solid was purified by chromatography on silica gel to give 114 mg of the title compound, i.e. the compound of the present invention, as a white solid which melts at 214-216 ° C.

¹ H NMR (CDCl ₃ ): δ 10.70 (s, 1H), 8.46 (dd, 1H), 7.87 (dd, 1H), 7.57 (s, 2H), 7.45 (m, 1H), 7.31 (s, 1H) , 6.35 (d, 1 H), 2.98 (d, 3 H), 2.24 (s, 3H).

Example 3

3-chloro-1- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6-[(methylamino) carbonyl] phenyl] -1 H-pyrazole-5-car Preparation of copy mid

Step A: Preparation of 3-chloro-N, N-dimethyl-1H-pyrazole-1-sulfonamide

In a solution of N-dimethylsulfamoylpyrazole (188.0 g, 1.07 mol) in anhydrous tetrahydrofuran (1500 mL) at −78 ° C., 2.5 M n-butyllithium (472 mL) in hexanes while maintaining the temperature below −65 ° C. , 1.18 mol) was added dropwise. When the addition was complete, the reaction mixture was kept at -78 [deg.] C. for 45 more minutes, after which a solution of hexachloroethane (279 g, 1.18 mol) in tetrahydrofuran (120 mL) was added dropwise. The reaction mixture was kept at -78 ° C for 1 hour, warmed to -20 ° C and the reaction was stopped with water (1 L). The reaction mixture was extracted with methylene chloride (4 x 500 mL) and the organic extracts were dried over magnesium sulfate and concentrated. The crude product was further purified by chromatography on silica gel using methylene chloride as eluent to afford 160 g of the title compound as a yellow oil.

¹ H NMR (CDCl ₃ ): δ 7.61 (s, 1 H), 6.33 (s, 1 H), 3.07 (d, 6 H).

Step B: Preparation of 3-chloropyrazole

To the trifluoroacetic acid (290 mL) was added dropwise 3-chloro-N, N-dimethyl-1H-pyrazole-1-sulfonamide (i.e. chloropyrazole product of step A) (160 g) and the reaction mixture was added. After stirring for 1.5 hours at room temperature it was concentrated under reduced pressure. The residue was taken up with hexanes, the insoluble solids were filtered off and the hexanes were concentrated to give the crude product as an oil. The crude product was further purified by chromatography on silica gel using ether / hexane (40:60) as eluent to give 64.44 g of the title product as a yellow oil.

¹ H NMR (CDCl ₃ ): δ 6.39 (s, 1 H), 7.66 (s, 1 H), 9.6 (br s, 1 H).

Step C: Preparation of 3-chloro-2- (3-chloro-1H-pyrazol-1-yl) pyridine

Carbonic acid in a mixture of 2,3-dichloropyridine (92.60 g, 0.629 mol) and 3-chloropyrazole (ie, the product of Step B) (64.44 g, 0.629 mol) in N, N-dimethylformamide (400 mL) Potassium (147.78 g, 1.06 mol) was added and the reaction mixture was heated to 100 ° C. for 36 hours. The reaction mixture was cooled to room temperature and slowly poured into ice water. The precipitated solid was filtered off and washed with water. The solid filter cake was taken with ethyl acetate, dried over magnesium sulfate and concentrated. The crude solid was chromatographed on silica gel using 20% ethyl acetate / hexane as eluent to afford 39.75 g of the title product as a white solid.

¹ H NMR (CDCl ₃ ): δ 6.43 (s, 1H), 7.26 (m, 1H), 7.90 (d, 1H), 8.09 (s, 1H), 8.41 (d, 1H).

Step D: Preparation of 3-chloro-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxylic acid

3-chloro-2- (3-chloro-1H-pyrazol-1-yl) pyridine (ie, the pyrazole product of Step C) in anhydrous tetrahydrofuran (400 mL) at -78 ° C (39.75 g, 186 mmol To a solution of 2.0 M lithium diisopropylamide (93 mL, 186 mmol) in tetrahydrofuran was added dropwise. After blowing carbon dioxide into the amber solution for 14 minutes, the solution turned a pale brownish yellow. The reaction was made basic with 1 N aqueous sodium hydroxide solution and extracted with ether (2 x 500 mL). The aqueous extract was acidified with 6 N hydrochloric acid and extracted with ethyl acetate (3 x 500 mL). The ethyl acetate extract was dried over magnesium sulfate and concentrated to give 42.96 g of the title product as off white solid. The product obtained in another run following the same procedure melted at 198-199 ° C.

¹ H NMR (DMSO-d ₆ ): δ 6.99 (s, 1H), 7.45 (m, 1H), 7.93 (d, 1H), 8.51 (d, 1H).

Step E: 2- [3-Chloro-1- (3-chloro-2-pyridinyl) -1 H-pyrazol-5-yl] -6-iodo-8-methyl-4H-3,1-benzox Preparation of Photo-4-one

To a solution of methanesulfonyl chloride (0.63 mL, 8.13 mmol) in acetonitrile (10 mL) in 3-chloro-1- (3-chloro-2-pyridinyl) -1H- in acetonitrile (5 mL) at 0 ° C. A mixture of pyrazole-5-carboxylic acid (ie, the carboxylic acid product of Step D) (2.0 g, 7.75 mmol) and triethylamine (1.08 ml, 7.75 mmol) was added dropwise. The reaction mixture was stirred at 0 ° C. for 15 minutes. Then 2-amino-3-methyl-5-iodobenzoic acid (ie, the product of Example 1, Step A) (2.14 g, 7.75 mmol) was added and stirring was continued for an additional 5 minutes. A solution of triethylamine (2.17 mL, 15.15 mmol) in acetonitrile (5 mL) was added dropwise while maintaining the temperature below 5 ° C. The reaction mixture was stirred at 0 ° C. for 40 minutes before methanesulfonyl chloride (0.63 mL, 8.13 mmol) was added. The reaction mixture was then warmed to room temperature and stirred overnight. The reaction mixture was then diluted with water (50 mL) and extracted with ethyl acetate (3 x 50 mL). The combined ethyl acetate extracts were washed sequentially with 10% aqueous sodium bicarbonate (1 × 20 mL) and brine (1 × 20 mL), dried (MgSO ₄ ) and concentrated to give 3.18 g of the title product as a yellow crude solid.

¹ H NMR (CDCl ₃ ): δ 8.55 (dd, 1H), 8.33 (s, 1H), 7.95 (dd, 1H), 7.82 (d, 1H), 7.45 (m, 1H), 7.16 (s, 1H) , 1.77 (s, 3 H).

Step F: 2- [3-Chloro-1- (3-chloro-2-pyridinyl) -1 H-pyrazol-5-yl] -6-cyano-8-methyl-4H-3,1-benzox Preparation of Photo-4-one

2- [3-chloro-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5-yl] -6-iodo-8-methyl-4H-3 in tetrahydrofuran (15 mL) To a solution of 1-benzoxazin-4-one (ie, the benzoxazinone product of step E) (600 mg, 1.2 mmol) copper iodide (137 mg, 0.72 mmol), tetrakis (triphenyl) at room temperature Phosphine) palladium (0) (416 mg, 0.36 mmol) and copper cyanide (I) (860 mg, 9.6 mmol) were added sequentially. The reaction mixture was heated to reflux overnight. When the reaction turned black, thin layer chromatography on silica gel confirmed the completion of the reaction. The reaction was diluted with ethyl acetate (20 mL) and filtered through Celite®, washed three times with 10% aqueous sodium bicarbonate solution and once with brine. The organic extract was dried (MgSO ₄ ) and concentrated under reduced pressure to give 397 mg of the title compound as a yellow crude solid.

¹ H NMR (CDCl ₃ ): δ 8.50 (q, 1H), 8.22 (d, 1H), 7.90 (dd, 1H), 7.67 (d, 1H), 7.45 (m, 1H), 7.15 (s, 1H) , 1.79 (s, 3 H).

Step G: 3-Chloro-1- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6- (methylamino) carbonyl] phenyl] -1 H-pyrazole-5 Preparation of Carboxamides

2- [3-chloro-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5-yl] -6-cyano-8-methyl-4H-3 in tetrahydrofuran (5 mL) To a solution of, 1-benzoxazin-4-one (e.g., the cyanobenzoxazinone product of step F) (100 mg, 0.25 mmol), methylamine (2.0 M solution in THF, 0.5 mL, 1.0 mmol) Was added dropwise and the reaction mixture was stirred for 5 minutes and thin layer chromatography on silica gel confirmed the completion of the reaction. The tetrahydrofuran solvent was evaporated under reduced pressure and the residual solid was purified by chromatography on silica gel to give the title compound as a white solid (52 mg) as a compound of the present invention which was decomposed in a melting apparatus higher than 140 ° C.

¹ H NMR (CDCl ₃ ): δ 10.55 (s, 1H), 8.45 (dd, 1H), 7.85 (dd, 1H), 7.55 (d, 2H), 7.40 (m, 1H), 6.97 (d, 1H) , 6.30 (d, 1 H), 2.98 (d, 3 H), 2.24 (d, 3H).

Example 4

3-chloro-1- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6- (aminocarbonyl) phenyl] -1 H-pyrazole-5-carboxamide Produce

2- [3-chloro-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5-yl] -6-cyano-8-methyl-4H-3 in tetrahydrofuran (5 mL) To a solution of 1-benzoxazin-4-one (ie, the cyano-benzoxazinone product of Example 3, step F) (100 mg, 0.25 mmol) was added ammonium hydroxide (0.5 mL, 12.8 mmol) at room temperature. Added dropwise. The reaction mixture was then stirred for 5 minutes and thin layer chromatography on silica gel confirmed the completion of the reaction. The tetrahydrofuran solvent was evaporated under reduced pressure and the residual solid was purified by chromatography on silica gel to give 55 mg of the title compound, a compound of the invention, as a white solid, which was decomposed in a melting apparatus higher than 255 ° C.

¹ H NMR (CDCl ₃ ): δ 10.50 (s, 1H), 8.45 (dd, 1H), 7.85 (dd, 1H), 7.66 (d, 1H), 7.61 (s, 1H), 7.41 (m, 1H) , 6.95 (s, 1H), 6.25 (bs, 1H), 5.75 (bs, 1H), 2.52 (s, 3H).

Example 5

3-bromo-1- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6-[(methylamino) carbonyl] phenyl] -1 H-pyrazole-5- Preparation of Carboxamide

Step A: Preparation of 3-Bromo-N, N-dimethyl-1H-pyrazole-1-sulfonamide

A solution of n-butyllithium (in hexanes) while maintaining the temperature below −60 ° C. in a solution of N, N-dimethylsulfamoylpyrazole (44.0 g, 0.251 mol) in anhydrous tetrahydrofuran (500 mL) at −78 ° C. 2.5 M, 105.5 mL, 0.264 mol) was added dropwise. Thick solids formed during the addition. On completion of the addition, the reaction mixture is further maintained for 15 minutes, followed by a solution of 1,2-dibromotetrachloroethane (90 g, 0.276 mol) in tetrahydrofuran (150 mL) while maintaining the temperature below -70 ° C. Was added drop wise. The reaction mixture turned to a clear orange color and continued stirring for 15 minutes. The -78 ° C bath was removed and the reaction was stopped with water (600 mL). The reaction mixture was extracted with methylene chloride (4 ×) and the organic extracts were dried over magnesium sulfate and concentrated. The crude product was further purified by chromatography on silica gel using methylene chloride-hexane (50:50) as eluent to afford 57.04 g of the title product as a clear colorless oil.

¹ H NMR (CDCl ₃ ): δ 3.07 (d, 6H), 6.44 (m, 1H), 7.62 (m, 1H).

Step B: Preparation of 3-bromopyrazole

3-bromo-N, N-dimethyl-1H-pyrazole-1-sulfonamide (ie, bromopyrazole product of Step A) (57.04 g) was added slowly to trifluoroacetic acid (70 mL). The reaction mixture was stirred at rt for 30 min and then concentrated under reduced pressure. The residue was taken up with hexanes, the insoluble solids were filtered off and the hexanes were evaporated to afford the crude product as an oil. The crude product was further purified by chromatography on silica gel using ethyl acetate / dichloromethane (10:90) as eluent to afford an oil. This oil was taken up with dichloromethane, neutralized with aqueous sodium bicarbonate solution, extracted with methylene chloride (3 ×), dried over magnesium sulfate and concentrated to give 25.9 g of the title product as a white solid. m.p. 61-64 ° C.

¹ H NMR (CDCl ₃ ): δ 6.37 (d, 1 H), 7.59 (d, 1 H), 12.4 (br s, 1 H).

Step C: Preparation of 2- (3-Bromo-1H-pyrazol-1-yl) -3-chloropyridine

To a mixture of 2,3-dichloropyridine (27.4 g, 185 mmol) and 3-bromopyrazole (ie, the product of Step B) (25.4 g, 176 mmol) in anhydrous N, N-dimethylformamide (88 mL) Potassium carbonate (48.6 g, 352 mmol) was added and the reaction mixture was heated to 125 ° C. for 18 hours. The reaction mixture was cooled to room temperature and poured into ice water (800 mL). A precipitate formed. The precipitated solid was stirred for 1.5 hours, filtered and washed with water (2 x 100 mL). The solid filter cake was taken with methylene chloride and washed sequentially with water, 1 N hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine. The organic extract was then dried over magnesium sulfate and concentrated to give 39.9 g of a pink solid. The crude solid was suspended in hexanes and stirred vigorously for 1 hour. The solid was filtered, washed with hexanes and dried to give the title product as an off-white powder (30.4 g), which was found to be> 94% pure by NMR. This material was used in step D without further purification.

¹ H NMR (CDCl ₃ ): δ 6.52 (s, 1H), 7.30 (dd, 1H), 7.92 (d, 1H), 8.05 (s, 1H), 8.43 (d, 1H).

Step D: Preparation of 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxylic acid

2- (3-bromo-1H-pyrazol-1-yl) -3-chloropyridine (ie, pyrazole product of Step C) in anhydrous tetrahydrofuran (250 mL) at -76 ° C (30.4 g, 118 to a solution of lithium diisopropylamide (118 mmol) in tetrahydrofuran was added dropwise at a rate such that the temperature was maintained below -71 ° C. The reaction mixture was stirred for 15 min at -76 ° C and blown with carbon dioxide for 10 min to warm to -57 ° C. The reaction mixture was warmed to -20 ° C and the reaction was stopped with water. The reaction mixture was concentrated and taken up with water (1 L) and ether (500 mL) followed by addition of aqueous sodium hydroxide solution (1 N, 20 mL). The aqueous extract was washed with ether and acidified with hydrochloric acid. The precipitated solid was filtered, washed with water and dried to give 27.7 g of the title product as a tan solid. Products from other runs that went through a similar process melted at 200-201 ° C.

¹ H NMR (DMSO-d ₆ ): δ 7.25 (s, 1H), 7.68 (dd, 1H), 8.24 (d, 1H), 8.56 (d, 1H).

Step E: 2- [3-Bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5-yl] -6-iodo-8-methyl-4H-3,1-benz Preparation of Oxazine-4-one

To a solution of methanesulfonyl chloride (0.54 ml, 6.94 mmol) in acetonitrile (15 mL) 3-bromo-1- (3-chloro-2-pyridinyl) -1H in acetonitrile (5 mL) at 0 ° C. A mixture of pyrazole-5-carboxylic acid (ie, the carboxylic acid product of Step D) (2.0 g, 6.6 mmol) and triethylamine (0.92 ml, 6.6 mmol) was added dropwise. The reaction mixture was stirred at 0 ° C. for 15 minutes. Then 2-amino-3-methyl-5-iodobenzoic acid (ie, the product of Example 1, Step A) (1.8 g, 6.6 mmol) was added and stirring continued for 5 minutes. Then, a solution of triethylamine (1.85 mL, 13.2 mmol) in acetonitrile (5 mL) was added dropwise while maintaining the temperature below 5 ° C. The reaction mixture was stirred at 0 ° C. for 40 minutes before methanesulfonyl chloride (0.54 ml, 6.94 mmol) was added. The reaction mixture was then warmed to room temperature and stirred overnight. The reaction mixture was then diluted with water (50 mL) and extracted with ethyl acetate (3 x 50 mL). The combined ethyl acetate extracts were washed sequentially with 10% aqueous sodium bicarbonate (1 × 20 mL) and brine (1 × 20 mL), dried (MgSO ₄ ) and concentrated to give 2.24 g of the title product as a yellow crude solid.

¹ H NMR (CDCl ₃ ): δ 8.55 (dd, 1H), 8.33 (d, 1H), 7.95 (dd, 1H), 7.85 (s, 1H), 7.45 (m, 1H), 7.25 (s, 1H) , 1.77 (s, 3 H).

Step F: 2- [3-Bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5-yl] -6-cyano-8-methyl-4H-3,1-benz Preparation of Oxazine-4-one

2- [3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5-yl] -6-iodo-8-methyl-4H- in tetrahydrofuran (15 mL) To a solution of 3,1-benzoxazin-4-one (ie, the benzoxazinone product of step E) (600 mg, 1.1 mmol), copper iodide (I) (126 mg, 0.66 mmol), tetrakis (triphenyl Phosphine) palladium (0) (382 mg, 0.33 mmol) and copper cyanide (I) (800 mg, 8.8 mmol) were added sequentially at room temperature. The reaction mixture was then heated to reflux overnight. When the reaction turned black, thin layer chromatography on silica gel confirmed the completion of the reaction. The reaction mixture was diluted with ethyl acetate (20 mL) and filtered through Celite®, washed three times with 10% sodium bicarbonate solution and once with brine. The organic extract was dried (MgSO ₄ ) and concentrated under reduced pressure to afford 440 mg of the title compound as a yellow crude solid.

¹ H NMR (CDCl ₃ ): δ 8.55 (m, 1H), 8.31 (d, 1H), 7.96 (dd, 1H), 7.73 (s, 1H), 7.51 (m, 1H), 7.31 (s, 1H) , 1.86 (s, 3 H).

Step G: 3-Bromo-1- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6-[(methylamino) carbonyl] phenyl] -1 H-pyrazole Preparation of -5-carboxamide

2- [3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5-yl] -6-cyano-8-methyl-4H- in tetrahydrofuran (5 mL) To a solution of 3,1-benzoxazin-4-one (ie, the cyanobenzoxazinone product of step F) (100 mg, 0.22 mmol) was added methylamine (2.0 M solution in THF, 0.5 mL, 1.0 mmol). The reaction mixture was added dropwise and the reaction mixture was stirred for 5 minutes and thin layer chromatography on silica gel confirmed the completion of the reaction. The tetrahydrofuran solvent was evaporated under reduced pressure and the residual solid was purified by chromatography on silica gel to give the title compound, the compound of the present invention, as a white solid (41 mg), which was decomposed in a melting apparatus higher than 180 ° C.

¹ H NMR (CDCl ₃ ): δ 10.55 (s, 1H), 8.45 (dd, 1H), 7.85 (dd, 1H), 7.57 (s, 2H), 7.37 (m, 1H), 7.05 (s, 1H) , 6.30 (d, 1 H), 2.98 (d, 3 H), 2.24 (s, 3H).

Example 6

3-bromo-1- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6- (aminocarbonyl) phenyl] -1 H-pyrazole-5-carboxamide Manufacture

2- [3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5-yl] -6-cyano-8-methyl-4H- in tetrahydrofuran (5 mL) Ammonium hydroxide (0.5 mL, 12.8 mmol) was added dropwise at room temperature to a solution of 3,1-benzoxazin-4-one (ie, the cyanobenzoxazinone product of Example 5, step F). The reaction mixture was then stirred for 5 minutes and thin layer chromatography on silica gel confirmed the completion of the reaction. The tetrahydrofuran solvent was evaporated under reduced pressure and the residual solid was purified by chromatography on silica gel to give the title compound as a white solid (36 mg) as a compound of the present invention with a melting point higher than 255 ° C.

¹ H NMR (CDCl ₃ ): δ 10.52 (s, 1H), 8.45 (dd, 1H), 7.85 (dd, 1H), 7.65 (s, 1H), 7.60 (s, 1H), 7.40 (m, 1H) , 7.05 (s, 1 H), 6.20 (bs, 1 H), 5.75 (bs, 1 H), 2.25 (s, 3 H).

Example 7

3-chloro-1- (3-chloro-2-pyridinyl) -N- [2-chloro-4-cyano-6-[(methylamino) carbonyl] phenyl] -1 H-pyrazole-5-carbon Preparation of copy mid

Step A: Preparation of 2-Amino-3-chloro-5-iodobenzoic acid

To a solution of 2-amino-3-chlorobenzoic acid (Aldrich, 5 g, 29.1 mmol) in N, N-dimethylformamide (30 mL) was added N-iodosuccinimide (5.8 g, 26 mmol), The reaction mixture was heated at 60 ° C. overnight. After heating was removed the reaction mixture was poured slowly into ice water (100 mL) and a pale brown solid precipitated. The solid was filtered, washed four times with water and placed in a vacuum oven at 70 ° C. to dry overnight. The desired intermediate was isolated as a light brown solid (7.2 g).

¹ H NMR (DMSO-d ₆ ): δ 7.96 (d, 1H), 7.76 (t, 1H).

Step B: 8-chloro-2- [3-chloro-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5-yl] -6-iodo-4H-3,1-benzox Preparation of Photo-4-one

To a solution of methanesulfonyl chloride (0.31 mL, 4.07 mmol) in acetonitrile (10 mL) was added 3-chloro-1- (3-chloro-2-pyridinyl) -1H- in acetonitrile (5 mL) at 0 ° C. A mixture of pyrazole-5-carboxylic acid (ie, the carboxylic acid product of Example 3, Step D) (1.0 g, 3.87 mmol) and triethylamine (0.54 mL, 3.87 mmol) was added dropwise. The reaction mixture was stirred at 0 ° C. for 15 minutes. Then 2-amino-3-chloro-5-iodobenzoic acid (ie, the product of Step A) (1.15 g, 3.87 mmol) was added and stirring was continued for a further 5 minutes. Then, a solution of triethylamine (1.08 mL, 7.74 mmol) in acetonitrile (5 mL) was added dropwise while maintaining the temperature below 5 ° C. The reaction mixture was stirred for 40 min at 0 ° C., then methanesulfonylchloride (0.31 mL, 4.07 mmol) was added. The reaction mixture was then warmed to room temperature and stirred overnight. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (3 x 50 mL). The combined ethyl acetate extracts were washed sequentially with 10% aqueous sodium bicarbonate (1 × 20 mL) and brine (1 × 20 mL), dried (MgSO ₄ ) and concentrated under reduced pressure. The residual solid was purified by chromatography on silica gel to give 575 mg of the title compound as a yellow crude solid.

¹ H NMR (CDCl ₃ ): δ 8.55 (q, 1H), 8.39 (d, 1H), 8.04 (d, 1H), 7.94 (dd, 1H), 7.45 (m, 1H), 7.19 (s, 1H) .

Step C: 8-chloro-2- [3-chloro-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5-yl] -6-cyano-4H-3,1-benzox Preparation of Photo-4-one

8-chloro-2- [3-chloro-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5-yl] -6-iodo-4H-3 in tetrahydrofuran (15 mL) To a solution of 1-benzoxazin-4-one (ie, the benzoxazinone product of step B) (575 mg, 1.1 mmol), copper (I) iodide (840 mg, 0.44 mmol), tetrakis (triphenylphosph) Pin) palladium (0) (255 mg, 0.22 mmol) and copper cyanide (I) (500 mg, 5.5 mmol) were added sequentially at room temperature. The reaction mixture was then heated to reflux overnight. When the reaction turned black, thin layer chromatography on silica gel confirmed the completion of the reaction. The reaction was diluted with ethyl acetate (20 mL) and filtered through Celite®, washed three times with 10% aqueous sodium bicarbonate solution and once with brine. The organic extract was dried (MgSO ₄ ) and concentrated under reduced pressure to give 375 mg of the title compound as a yellow crude solid.

¹ H NMR (CDCl ₃ ): δ 8.55 (q, 1H), 8.36 (d, 1H), 7.95 (m, 2H), 7.5 (m, 1H).

Step D: 3-Chloro-1- (3-chloro-2-pyridinyl) -N- [2-chloro-4-cyano-6-[(methylamino) carbonyl] phenyl] -1 H-pyrazole- Preparation of 5-Carboxamide

8-chloro-2- [3-chloro-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5-yl] -6-cyano-4H-3 in tetrahydrofuran (5 mL) To a solution of 1-benzoxazin-4-one (ie the cyanobenzoxazinone product of step C) (187 mg, 0.446 mmol) was added dropwise methylamine (2.0 M solution in THF, 0.5 mL, 1.0 mmol). The reaction mixture was stirred for 5 minutes, at which time thin layer chromatography on silica gel confirmed the completion of the reaction. The tetrahydrofuran solvent was evaporated under reduced pressure and the residual solid was purified by chromatography on silica gel to give 49 mg of the title compound, a compound of the present invention, as a white solid which melts at 197-200 ° C.

¹ H NMR (CDCl ₃ ): δ 10.05 (bs, 1H), 8.45 (q, 1H), 7.85 (dd, 1H), 7.70 (d, 1H), 7.59 (d, 1H), 7.38 (m, 1H) , 7.02 (s, 1 H), 6.35 (d, 1 H), 2.94 (d, 3 H).

The following compounds of Table 1 can be prepared by the methods described herein in combination with methods known in the art. In the table the following abbreviations are used: t is tertiary, s is secondary, n is normal, i is iso, Me is methyl, Et is ethyl, Pr is propyl, i-Pr is isopropyl, Bu is butyl, CN Means cyano.

Formulation / Utility

The compounds of the present invention will generally be used as a formulation or composition with a carrier suitable for agricultural or non-agronomic uses comprising one or more liquid diluents, solid diluents or surfactants. The components of the formulation or composition are selected to suit the physical properties of the active ingredients, the method of application and environmental factors such as soil type, humidity and temperature. Useful formulations include liquids such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and / or suspensions), and the like, which can be optionally concentrated to gel. Useful formulations further include solids such as dust, powders, granules, pellets, tablets, films, and the like, which may be water dispersible (wettable) or water soluble. The active ingredients can be (micro) encapsulated, further made into suspensions or solid preparations, or alternatively encapsulated (or overcoated) the whole preparation of the active ingredient. Encapsulation can control or delay the release of the active ingredient. Injectable formulations can be dispersed in a suitable medium and used in an injection volume of about one hundred to several hundred liters per hectare. High concentration compositions are mainly used as intermediates for further formulation.

Such formulations will typically contain an effective amount of the active ingredient, diluent and surfactant in the approximate ranges below, which add up to 100% by weight.

Weight percent Active ingredient diluent Surfactants Water dispersible and water soluble granules, tablets and powders 5-90 0-94 1-15 Suspensions, emulsions, solutions (including emulsifiable concentrates) 5-50 40-95 0-15 Dust 1-25 70-99 0-5 Granules and pellets 0.01-99 5-99.99 0-15 High concentration composition 90-99 0-10 0-2

Typical solid diluents are described in Watkins, et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950. McCutcheon's Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, as well as in Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964, lists surfactants and recommended uses. All formulations may contain small amounts of additives to reduce foam, solidification, corrosion, microbial growth, and the like, or thickeners to increase viscosity.

Surfactants are, for example, polyethoxylated alcohols, polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acid esters, dialkyl sulfosuccinates, alkyl sulfates, alkylbenzene sulfonates, organosilicones , N, N-dialkyltaurate, lignin sulfonate, naphthalene sulfonate formaldehyde condensates, polycarboxylates and polyoxyethylene / polyoxypropylene block copolymers. Solid diluents include, for example, clays (eg bentonite, montmorillonite, attapulgite and kaolin), starch, sugars, silica, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate and sodium bicarbonate, and sodium sulfate . Liquid diluents are, for example, water, N, N-dimethylformamide, dimethyl sulfoxide, N-alkylpyrrolidone, ethylene glycol, polypropylene glycol, paraffin, alkylbenzenes, alkalnaphthalene, olive oil, castor oil, flax Phosphorus oil, tung oil, sesame oil, corn oil, peanut oil, cottonseed oil, soybean oil, rapeseed oil and coconut oil, fatty acid esters, ketones (e.g. cyclohexanone, 2-heptanone, isophorone and 4-hydroxy- 4-methyl-2-pentanone) and alcohols (eg, methanol, cyclohexanol, decanol and tetrahydropulfuryl alcohol).

Solutions containing emulsifiable concentrates can be prepared by simply mixing the components. Dust and powder can be prepared by blending and grinding, usually in hammer mills or fluid energy mills. Suspensions are usually prepared by wet-milling. See, for example, US Pat. No. 3,060,084. Granules and pellets can be prepared by spraying the active material onto preformed granular carriers or by agglomeration techniques. Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp 147-48, Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and PCT Publication WO 91 See / 13546. Pellets may be prepared as described in US Pat. No. 4,172,714. Water dispersible and water soluble granules can be prepared as taught in US Pat. Nos. 4,144,0505, 3,920,442 and DE 3,246,493. Tablets may be prepared as taught in US Pat. Nos. 5,180,587, 5,232,701 and 5,208,030. Films can be prepared as taught in GB 2,095,558 and US Pat. No. 3,299,566.

Additional information on formulation techniques can be found in T.S. Woods, "The Formulator's Toolbox-Product Forms for Modern Agriculture" in Pesticide Chemistry and Bioscience, The Food-Environment Challange, T. Brooks and T.R. Roberts, Eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133, see also US Pat. No. 3,235,361, column 6, line 16 to column 7, line 19 and Examples 10-41; US Pat. Nos. 3,309,192, column 5, line 43 to column 7, 62 and examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169 -182; US Patent Nos. 2,891,855, column 3, line 66 to column 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; And Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989.

In the examples below, all percentages are by weight and all formulations are prepared by conventional methods. The compound number refers to the compound in Index A.

Example A

Wettable powder

Compound 1 65.0% Dodecylphenol Polyethylene Glycol Ether 2.0% Sodium ligninsulfonate 4.0% Sodium Silicoaluminate 6.0% Montmorillonite (calcined) 23.0%

Example B

Granules

Compound 1 10.0% Aterpulgite granules (low volatiles, 0.71 / 0.30 mm; U.S.S. No. 25-50 sieve) 90.0%

Example C

Extruded pellets

Compound 1 25.0% Anhydrous sodium sulfate 10.0% Crude calcium ligninsulfonate 5.0% Sodium alkylnaphthalenesulfonate 1.0% Calcium / Magnesium Bentonite 59.0%

Example D

Emulsifiable concentrate

Compound 1 20.0% Blend of Oil Soluble Sulfonate and Polyoxyethylene Ether 10.0% Isophorone 70.0%

Example E

Granules

Compound 1 0.5% Cellulose 2.5% Lactose 4.0% Corn flour 93.0%

The compounds of the present invention are characterized by good metabolic and / or soil residual patterns and exhibit activity to control the spectrum of agricultural and non-agronomic invertebrate pests. The compounds of the present invention also provide good leaf and / or soil-application infiltrates in plants that exhibit translocation to protect leaves and other plant parts that are not in direct contact with the pesticidal composition comprising the compounds of the present invention. systemicity). ("Invertebrate pest control" in this disclosure means the inhibition (including lethal) of growth of invertebrate pests that causes a significant reduction in feeding or other damage or damage caused by pests; related expressions are similarly defined. The term “invertebrate pest” as referred to in this disclosure includes arthropods, gastropods and nematodes of economic importance as pests. The term “arthropod” includes insects, mites, spiders, scorpions, centipedes, millipedes, coworms, and conjoinants. The term "gastropod" includes snails, slugs and other Stylommatophora. The term "nematode" includes all kinds of parasites, such as nematodes, filaments, and herbivorous nematodes (Nematoda), trematoda, Acanthocephala, and tapeworm (Cestoda). Those skilled in the art will appreciate that not all compounds have the same effect on all pests. The compounds of the present invention show activity against economically important agricultural and non-agronomic pests. The term "agriculture" refers to the production of crops such as for food and fiber and includes grains (e.g. wheat, oats, barley, rye, rice, corn), soybeans, vegetable complexes (e.g. lettuce, cabbage, Cultivation of tomatoes, beans), potatoes, sweet potatoes, grapes, cotton, and arbor fruit (eg, pome fruit, nucleus, and citrus). The term "non-agricultural" refers to other gardening (eg, forests, greenhouses, seedlings or ornamental plants that do not grow in the field), grass (commercial, golf, residential, recreational, etc.), wood products, the public (human) and animals Health, household and commercial construction, household, and storage product applications or pests. Invertebrate Pest Control Because of its spectrum and economic importance, controlling invertebrate pests protects agricultural crops of cotton, corn, soybeans, rice, vegetable complexes, potatoes, sweet potatoes, grapes, and arbors (induced by invertebrate pests). From damage or damage) is a preferred embodiment of the present invention. Agricultural or non-agronomic pests include larvae of the Lepidoptera, such as the insectworms of the Noctuidae, the cutworms, the looper, and the heliothines (e.g., Fall armyworm ( Spodoptera fugiperda JE Smith), Beet armyworm ( Spodoptera exigua Hubner), Black cutworm ( Agrotis ipsilon Hufnagel), Cabbage looper ( Trichoplusia ni Hubner), Tobacco moth ( tabacco budworm; Heliothis virescens Fabricius)); Pyralidae insects, casebearers, webworms, coneworms, cabbageworms and skeletonizers (e.g. Europe Corn corn borer ( Ostrinia nubilalis Huebner), navel orangeworm ( Amyelois transitella Walker), corn root webworm ( Crambus caliginosellus Clemens), sod webworm ( Herpetogramma licarsisalis Walker) ); Leafroller, budworm, seed worm, and fruit worm (e.g., codling moth; Cydia pomonella Linnaeus) in Tortricidae Grape berry moth ( Endopiza viteana Clemens), oriental fruit moth ( Grapholita molesta Busck); And many other economically important other species, such as diamondback moth ( Plutella xylostella Linnaeus), pink bollworm ( Pectinophora gossypiella Saunders), gypsy moth ( Lymantria dispar Linnaeus); Larvae and adults (Borthal cockroach; Blatta orientalis Linnaeus), Asian cockroach ( Blatella asahinai Mizukubo), including larvae and adults (Blattodea), including the cockroaches of the Bratellidae and the Blattidae, German cockroach ( Blatella germanica Linnaeus), brownbanded cockroach ( Supella longipalpa Fabricius), American cockroach ( Periplaneta americana Linnaeus), brown cockroach ( Periplaneta brunnea Burmeister), Madeira cockroach (Madeira) cockroach; Leucophaea maderae Fabricius)); Leaf-feeding larvae and adults (eg, boll weevil; Anthonomus grandis Boheman), rice weevil, including Coleoptera, including weevil of Anthrabidae, Bruchidae and Curculionidae (rice water weevil; Lissorhoptrus oryzophilus Kuschel), grain weevil ( Sitophilus granarius Linnaeus), rice weevil ( Sitophilus oryzae Linnaeus); Chleasomelidae flea beetle, cucumber leaf beetle, rootworm, leaf beetle, potato beetle and leafminer (eg Colorado potato) Leafworm (Colorado potato beetle; Leptinotarsa decemlineata Say), western corn rootworm ( Diabrotica virgifera virgifera LeConte); Scarab and other beetles of Scaribaeidae (eg Japanese beetle; Popillia japonica Newman and European chafer; Rhizotrogus majalis Razoumowsky); Carpet beetle of the family Dermestidae; Wireworm of Elateridae; Bark beetle of Scolytidae; And floor beetle of Tenebrionidae. In addition, agricultural and non-agricultural pests include the herb beetle including Forficulidae's beetle (for example, European earwig; Forficula auricularia Linnaeus, black earwig; Chelisoches morio Fabricius). Adults and larvae of the neck (Dermaptera); Adults and larvae of Hemiptera and Homoptera, such as plant bugs of the Miridae, Cicadidae cicadas, leafhoppers of Cicadellidae (e.g. Empoasca spp) .)), Fulgoroidae and Delphacidae, Planthopper, Membracidae, Treehopper, Psyllidae, Pyllidae, Aleyrodidae whiteflies, Aphids of Aphididae, Phylloxera of Phylloxeridae, mealybugs of Pseudococcidae, Coccidae, Diaspididae And scale bug of Margarodidae, lace bug of Tingidae, stink bug of Pentatomidae and cinch bug of Lygaeidae. spp bug) (for example, Bulletin Versus (Blissus).) and the Seed bugs, spiderbugs of the Cercopidae, squash bugs of the Coreidae, and red bugs and cotton stainers of the Pyrrhocoridae. cotton stainer). Also as agricultural and non-agricultural pests, adults and larvae of Acari (mite), such as spider mites and red mites of the Tetranychidae (eg, European red mite; Panonychus ulmi Koch) , Two spotted spider mite ( Tetranychus urticae Koch), McDaniel mite ( Tetranychus mcdanieli McGregor), flat mite of Tenuipalpidae (e.g. citrus flat mite ( Brevipalpus lewisi McGregor)), Rust and bud mite of Eriophyidae and other foliar feeding mites and important mites for human and animal health, namely Epidermoptidae Dust mite, follicle mite of the Acne mite family, grain mite of the Glycyphagidae, mite of the Ixodidae (for example, deer tick ( Ixodes scapularis Say), Australia) bottle Tick (Australian paralysis tick; Ixodes holocyclus Neumann ), American dog tick (American dog tick; Dermacentor variabilis Say ), Lone Star ticks (lone star tick; Amblyomma americanum Linnaeus ) and Thoreau Petit de (Psoroptidae), motif used on the skin (Pyemotidae) And scab and itch mites with Sarcoptidae; adults and larvae of Orthoptera, including grasshoppers, locusts and crickets (eg Migratory grasshoppers (eg Melanoplus sanguinipes Fabricius, M. differentialis Thomas), American grasshoppers (eg Schistocerca americana Drury), desert locust; Schistocerca gregaria Forskal, migratory locust ( Locusta migratoria Linnaeus), bush locust ( Zonocerus spp. ), House cricket ( Acheta domesticus Linnaeus), mole crickets; Gryllotalpa sp ; Adults and larvae of Diptera, for example leafminer, midge, fruit flies (Tephritidae), frit flies (for example Oscinella frit Linnaeus), Soil maggots, house fly (e.g. Musca domestica Linnaeus), lesser house fly (e.g. Fannia canicularis Linnaeus, F. femoralis Stein, stable flies) (Eg Stomoxys calcitrans Linnaeus), face flies, horn flies, blow flies (eg Chrysomya spp., Phormia spp.), And other muskoid flies Mucoid fly pests, horse flies (e.g. Tabanus spp.), Bot flies (e.g. Gastrophilus spp., Oestrus spp.), Cow grub ( E.g. Hypoderma spp.), Deer flies (e.g. Chrysops spp.), Ked (e.g. Melophagus ovinus Linnaeus) and other Brachycera, mosquitoes (e.g. For example, Ae des spp., Anopheles spp., Culex spp.), black flies (eg Prosimulium spp., Simulium spp.), biting midges, sand flies, sand flies (sciarids), and other Nematocera; Adults and larvae of Thysanoptera, including onion thrips ( Thips tabaci Lindeman), flower thrips ( Frank liniella spp.) And other foliar feeding thrips; Insect pests of Hymenoptera including ants (e.g. red carpenter ant; Camponotus ferrugineus Fabricius), black carpenter ant ( Camonotus pennsylvanicus De Geer), Pharaoh ant; Monomorium pharaonis Linnaeus, little fire ant; Wasmannia auropunctata Roger, fire ant; Solenopsis geminata Fabricius, red imported fire ant; Solenopsis invicta Buren, Argentine ant; Iridomyrmex humilis Mayr Crazy ant ( Paratrechina longicornis Latreille), paved ant ( Tetramorium caespitum Linnaeus), cornfield ant ( Lasius alienus Foerster), odorous house ant ( Tapinoma sessile Say), Bees (including Carpenter bees), bumblebees, hornets, yellow jackets, wasps and wasps ( Neodiprion spp . ; Cephus spp. ); Eastern subterranean termite ( Reticulitermes flavipes Kollar), Western subterranean termite ( Reticulitermes hesperus Banks), Taiwan subterranean termite ( Corptotermes formosanus Shiraki), Western dry Indian termite Insect pests of Isoptera, including Incisitermes immigrans Snyder) and other economically important termites; Insect pests of Thysanura, such as silverfish ( Lepisma saccharina Linnaeus) and firebrat ( Thermobia domestica Packard); Head louse; Pediculus humanus capitis De Geer, body louse; Pediculus humanus humanus Linnaeus, chicken body louse; Menacanthus stramineus Nitszch, dog biting louse; Trichodectes canis De Geer, Fluff louse; Goniocotes gallinae De Geer; sheep body louse; Bovicola ovis Schrank; short-nosed cattle louse; Haematopinus eurysternus Nitzsch; long-nosed cattle louse; Linognathus vituli Linnaeus) and other insect pests of Mallopha, including other lick and chew parasites that attack humans and animals; Oriental rat flea ( Xenopsylla cheopis Rothschild), cat flea ( Ctenocephalides felis Bouche), dog flea ( Ctenocephalides canis Curtis), hen flea ( Ceratophyllus gallinae Schrank), stilt flea insect pests of Siphonoptera, including sticktight flea; Echidnophaga gallinacea Westwood, human flea; Pulex irritans Linnaeus, and other fleas that plague mammals and birds. Further invertebrate pests include spiders of Araneae, such as the brown recluse spider ( Loxosceles reclusa Gertsch & Mulaik) and the black widow spider ( Latrodectus mactans Fabricius), and the Scutigeromorpha. Centipedes such as house centipede ( Scutigera coleoptrata Linnaeus). The compounds of the present invention also represent economically important members of the family Strongylida, Ascaridida, Oxyurida, Rhabditida, Spirurida and Enoplida. Nematodes, nematodes, reptiles and oral nematodes, including, but not limited to, economically important agricultural pests (ie, root knot nematode, Root nematode of Melodogyne) Lesion nematode of the genus Pratylenchus , stubby root nematode of the genus Trichodorus , etc., and animal and human health pests (i.e. all economically important fluke, tapeworms) tapeworms and roundworms, such as Strongylus vulgaris in horses, Toxocara canis in dogs , Haemonchus contortus in sheep, Dirophyllaria imtis rai in dogs Dirofilaria i mmitis Leidy), horse Anoplocephala perfoliata , ruminant Pasciola hepatica Linnaeus, and the like.

The compounds of the present invention are particularly suitable for pests of Lepidoptera (eg, Alabama argillacea Huebner (cotton leaf worm)), Archips argyrospila Walker (fruit tree leaf roller), European leafer ( A. rosana Linnaeus (European leaf roller) and other Archips species, Chilo suppressalis Walker (rice stem borer), Cnaphalocrosis medinalis Guenee (rice leaf roller), Corn Root Spider House Insects ( Crambus caliginosellus Clemens (corn root webworm)), Crambus teterrellus Zincken (bluegrass webworm), Cydia pomonella Linnaeus (codling moth), Earias insulana Boisduval (spiny bollworm) ), Earias vittella Fabricius (spotted bollworm), Helicoverpa armigera Huebner (American bollworm), Corn earworm ( Helicoverpa zea Boddie; corn earworm), Heliothis virescens Fabricius; tobacc o budworm, Herpetogramma licarsisalis Walker (sod webworm), grape berry moth ( Lobesia botrana Denis & Schiffermueller (grape berry moth), Pectinophora gossypiella Saunders (pink bollworm), Phyllocnistis citrella Stainton (citrus leafminer)), Pieris brassicae Linnaeus (large white butterfly), Pieris rapae Linnaeus (small white butterfly), Plutella xylostell a Linnaeus (diamondback moth), Beet night moth ( Spodoptera exigua Huebner (beet armyworm)), Spodoptera litura Fabricius (tobacco cutworm, cluster caterpillar), Spodoptera frugiperda JE Smith (fall armyworm), Trichoplusia ni Huebner (cabbage looper) and It has a particularly high activity against tomato leaf beetle ( Tuta absoluta Meyrick (tomato leafminer)). In addition, the compounds of the present invention are Acyrthisiphon pisum Harris (pea aphid), Aphis craccivora Koch (cowpea aphid), Aphis fabae Scopoli (black bean aphid), Cotton aphid, Melon aphid (Aphis gossypii Glover (cotton aphid, melon aphid)), apple aphid (Aphis pomi De Geer (apple aphid )), RY Ria aphid (Aphis spiraecola Patch (spirea aphid) ), foxglove aphid (Aulacorthum solani Kaltenbach (foxglove aphid) ) , Strawberry aphid ( Chaetosiphon fragaefolii Cockerell (strawberry aphid)), Russian wheat aphid ( Diuraphis noxia Kurdjumov / Mordvilko (Russian wheat aphid)), rose apple aphid ( Dysaphis plantaginea Paaserini (rosy apple aphid)) oma (woolly apple aphid)), Hydopterus pruni Geoffroy (mealy plum aphid), Turnip aphids ( Lipaphis erysimi Kaltenbach (turnip aphid)), Grain aphids ( Metopolophium dirrhodum Walker (cereal aphid) )), Potato aphid ( Macrosipum euphorbiae Thomas (potato aphid)), peach-potato aphid, green peach aphid ( Myzus persicae Sulzer (peach-potato aphid, green peach aphid)), lettuce aphid ( Nasonovia ribisnigri Mosley (lettuce aphid)) , Root Aphids and Lumps Aphids ( Pemphigu s spp. (root aphids and gall aphids), Rhopalosiphum maidis Fitch (corn leaf aphid), Rhopalosiphum padi Linnaeus (bird cherry-oat aphid), and Schizaphis graminum Rondani (greenbug) , Sitobion avenae Fabricius (English grain aphid), Spotted Alfalfa Aphid ( Therioaphis maculata Buckton (spotted alfalfa aphid)), Toxoptera aurantii Boyer de Fonscolombe (black citrus aphid), and Brown Tangerine Aphid Toxoptera citricida Kirkaldy (brown citrus aphid)); Adele Gid (Adelges spp (adelgids).) ; Walnut piloxera ( Phylloxera devastatrix Pergande (pecan phylloxera)); Tobacco powder, sweet potato powder ( Bemisia tabaci Gennadius (tobacco whitefly, sweetpotato whitefly)), silver leaf powder ( Bemisia argentifolii Bellows & Perring (silverleaf whitefly)), tangerine powder ( Dialeurodes citri Ashmead (citrus whitefly)) and greenhouse powder ( Taleurodes vaporariorum) Westwood (greenhouse whitefly)); Empoasca fabae Harris (potato leafhopper), Laodelphax striatellus Fallen (smaller brown planthopper), Macrolestes quadrilineatus Forbes (aster leafhopper), Nephotettix cinticeps Uhler (green leafhopper), rice Nemotettix nigropictus Stal (rice leafhopper), Nilaparvata lugens Stal (brown planthopper), Peregrinus maidis Ashmead (corn planthopper), Sogatella furcifera Horvath (white-backed planthopper) Sogatodes orizicola Muir (rice delphacid); Typhlocyba pomaria McAtee white apple leafhopper, Erythroneoura spp. (Grape leafhoppers); Cycle cicada ( Magicidada septendecim Linnaeus (periodical cicada)); Cotton cushion scale ( Icyrya purchasi Maskell (cottony cushion scale)), San Joss Scale ( Quadraspidiotus perniciosus Comstock (San Jose scale)); Planococcus citri Risso (citrus mealybug); Other Millybug complex ( Pseudococcus spp. (Other mealybug complex)); It has commercially significant activity against members from Homoptera, including Cacopsylla pyricola Foerster (pear psylla) and Trioza diospyri Ashmead (persimmon psylla). In addition, the compound is a green odor bug ( Acrosternum hilare Say (green stink bug)), squash bug ( Ansa tristis De Geer (squash bug)), chin bug ( Blissus leucopterus leucopterus Say (chinch bug)), cotton lace bug ( Corythuca gossypii Fabricius (cotton lace bug)), tomato bug ( Cyrtopeltis modesta Distant (tomato bug)), cotton stainer ( Dysdercus suturellus Herrich-Schaeffer (cotton stainer)), brown stink bug ( Euchistus servus Say (brown stink bug)), Euchistus variolarius Palisot de Beauvois (one-spotted stink bug), Graptosthetus spp. (Complex of seed bugs), Leptoglossus corculus Say (leaf-footed pine seed bug) ), Lygus lineolaris Palisot de Beauvois (tarnished plant bug), Nezara viridula Linnaeus (southern green stink bug), Oebalus pugnax Fabricius (rice stink bug), bulk milk Weed Worm ( Oncopelt It is active against members of Hemiptera, including us fasciatus Dallas (large milkweed bug)) and Pseudatomoscelis seriatus Reuter (cotton fleahopper). Other insect necks controlled by the compounds of the present invention include Thysanoptera (e.g., Frankliniella occidentalis Pergande (western flower thrip), Scirthothrips citri Moulton (citrus thrip), soybeans. Snail toothrips variabilis Beach (soybean thrip), and onion thrip (Thips tabaci Lindeman (onion thrip)); and Coleoptera (e.g., Leptinotarsa decemlineata Say (Colorado potato beetle)) , a skipjack in the Mexican bean beetle (Epilachna varivestis Mulsant (Mexican bean beetle )) and skipjack in the roots (Agriotes), skipjack in ginmom (Athous) or skipjack in (Limonius).

The compounds of the invention may also be used as insecticides, fungicides, nematicides, fungicides, acaricides, growth regulators such as root stimulants, chemical infertility agents, signaling compounds, insect repellents, attractants, pheromones, feeding stimulants, other biological activities Compounds or one or more other biologically active compounds or agents, including pathogenic bacteria, viruses, or fungi, may be mixed to form multicomponent insecticides that provide a broader range of agricultural and non-agricultural uses. Accordingly, the present invention also relates to a composition comprising a biologically effective amount of a compound of formula 1 and an effective amount of one or more additional biologically active compounds or agents, and may further comprise one or more surfactants, solid diluents or liquid diluents. . Examples of such biologically active compounds or agents that may be formulated with the compounds of the invention include insecticides such as abamectin, acetate, acetamiprid, acetoprole, amidoflumet (S-1955), avermectin, Azadirachtin, azinfos-methyl, bifenthrin, bifenazate, bistrifluron, buprofezin, carbofuran, chlorfenapyr, chlorfluazuron, chlorpyriphos, chlorpyrifos-methyl, Chromafenozide, clothianidine, cyfluthrin, beta-cifluthrin, sihalothrin, lambda-sihalothrin, cipermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dipple Rubenzuron, Dimethoate, Dinotefuran, Diophenolran, Emamtine, Endosulfan, Espenvalrate, Ethiprole, Phenoticcarb, Phenoxycarb, Phenpropartin, Penvalerate, Fipronil, Floricamid, Flucitrinate, Tau-Fle Valinate, flufenerim (UR-50701), flufenoxuron, gamma-chalotrine, halopenozide, hexaflumuron, imidacloprid, indoxacarb, isofenfoss, lufenuron, malathion, met Aldehyde, Metamidophos, Methitathione, Methyl, Metoprene, Methoxycyclo, Methoxyphenozide, Metofluthrin, Monoclotophos, Methoxyphenozide, Novaluron, Nobiflumuron ( XDE-007), oxamyl, parathion, parathion-methyl, permethrin, forate, posalone, phosphmet, phosphamidone, pyrimikab, propenophosphate, propfluthrin, protrifenbut, pimetro Gin, pyridalyl, pyriproxyfen, rotenone, S1812 (Valent) spinosad, spiromesifen (BSN 2060), sulfophosphate, tebufenozide, tflubenzuron, tefluthrin, terbufos, tetra Chlorbinfoss, tiacloprid, thiamethoxam, thiodicarb, thiosulfato-sodium, tolfenpyrad, Ralph Romero trim, tri chlor phones and triple base muron; Fungicides such as acibenzola, S-methyl, azoxystrobin, benalzi-M, ventiavalicarb, benomil, blasticidine-S, bordeaux mixture (tribasic copper sulfate), boscalid, bro Muconazole, butiobate, carpropamide, captapol, captan, carbendazim, chloroneb, chlorothalonil, clotrimazole, copper oxychloride, copper salt, simoxanyl, cyazopamide, cyflufenamide , Ciproconazole, Cyprodinyl, Diclocimet, Diclomezine, Dichloran, Difenokazole, Dimethomorph, Dimoxistrobin, Dinicoconazole, Diconazole-M, Dodine, Edifenforce , Epoxyconazole, etaboksam, pamoksadon, phenarimol, fenbuconazole, phenhexamide, phenoxanyl, fenpiclonil, phenpropidine, phenpropimorph, fentin acetate, fentin hydroxide, Fluazinam, Fludioxonyl, Flumorph, Fluoxastrobin, Fluquinconazole, Flu Silazole, flutolanyl, flutriafol, polpet, phosphetyl-aluminum, furalacyl, furametapyr, guazatin, hexaconazole, himmezazole, imazaryl, imbenconazole, iminottadine, if Conazole, Iprobenfos, Iprodione, Iprovalicarb, Isoconazole, Isoprothiolane, Kasugamycin, Cresoxime-Methyl, Mancozeb, Maneb, Mephenoxam, Mepanapyrim, Mepronyl, Metallaxyl, metconazole, metominostrobin / phenominostrobin, methraphenone, myconazole, myclobutanyl, neo-asozin (ferric methane arsenate), noarimol, orizastrobin, Oxadixyl, oxpoconazole, fenconazole, penicuron, picobenzamide, picoxistrobin, probenazole, prochloraz, propamocarb, propiconazole, proquinazide, prothioconazole, pyraclozol Strovin, pyrimethanyl, pyriphenox, pyroquilon, quinoxyphene, silthiofam, Meconazole, sifconazole, spiroxamine, sulfur, tebuconazole, tetraconazole, thiadinil, thibendazole, tifluzamide, thiophanate-methyl, thiram, tolylufluoride, triadi Mepon, triadimenol, triarimol, tricyclazole, trixystrobin, triflumizol, tripolin, triticazole, uniconazole, validamycin, vinclozoline and oxamide; Nematicides such as aldicarb, oxamyl and phenamifos; Fungicides such as streptomycin; Acaricides such as amitraz, chinomethionate, chlorobenzylate, cyhexatin, dicopol, dienochlor, ethoxazole, phenazaquin, fenbutatin oxide, phenpropatrine, fenpyromate, Hexithiax, propargite, pyridaben and tebufenpyrad; And biological agents such as ssp. Bacillus thuringiensis , Bacillus thuringiensis delta endotoxin, baculovirus, including aizawai and kurstaki , and insect pathogenic bacteria, viruses, and fungi to be. The compounds of the present invention and compositions thereof can be applied to plants genetically modified to express proteins (eg, Bacillus thuringiensis toxin) that are toxic to invertebrate pests. The effect of exogenously applied invertebrate pest control of the invention may be synergistic with the expressed toxin protein.

General references for these agricultural protection agents are described in The Pesticide Manual, 12th Edition, C.D.S. Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2000].

Preferred insecticides and acaricides for mixing with the compounds of the invention are pyrethroids such as acetamiprid, cipermethrin, sihalothrin, cifluthrin, beta-cifluthrin, espenvalrate, penvalerate and Tralomethrin; Carbamates such as phenoticarb, metomil, oxamyl and thiodicarb; Neonicotinoids such as clotianidine, imidacloprid and thiacloprid; Neuronal sodium channel blockers such as indoxacarb; Insecticidal macrocyclic lactones such as spinosad, abamectin, avermectin and emamectin; γ-aminobutyric acid (GABA) antagonists such as endosulfan, etiprolol and fipronil; Insecticidal ureas such as flufenoxuron and triflumuron; Larva hormone mimetics such as diophenollan and pyriproxyfen; Pymetrozine; And amitraz. Preferred biological agents for mixing with the compounds of the present invention include natural and transgenic viral insecticides and insect pathogenic fungi, including members of the family Bacillus thuringiensis and Bacillus thuringiensis delta endotoxin and Baculoviridae. .

Most preferred mixtures are mixtures of a compound of the invention with sihalothrin; Mixtures of a compound of the invention with beta-cifluthrin; Mixtures of the mixture of the present invention and esfenvalerate; Mixtures of a compound of the invention with metomil; Mixtures of a compound of the invention with imidacloprid; Mixtures of a compound of the invention with thiacloprid; Mixtures of a compound of the invention with indoxacarb; Mixtures of the compounds of the invention with abamectin; Mixtures of a compound of the present invention with endosulfan; Mixtures of a compound of the invention with etiprolol; Mixtures of a compound of the invention with fipronil; Mixtures of a compound of the present invention with flufenoxuron; Mixtures of a compound of the invention with pyriproxyfen; Mixtures of compounds of the invention and pymetrozine; Mixtures of compounds of the invention with amitraz; Mixtures of a compound of the invention with Bacillus thuringiensis Aizawa or Bacillus thuringiensis kurstaki, and mixtures of a compound of the invention with Bacillus thuringiensis delta endotoxin.

In certain instances, other invertebrate pest control compounds or combinations of agents having similar control ranges but different modes of action would be particularly advantageous for resistance management. Thus, the compositions of the present invention may further comprise a biologically effective amount of one or more additional invertebrate pest control compounds or agents having similar control ranges but different modes of action. In addition, contacting a biologically effective amount of a compound of the present invention with a plant or plant genetically modified to express a plant protective compound (eg, a protein) can provide a broader range of plant protection and management of resistance May be advantageous.

Invertebrate in agricultural and non-agronomic applications by applying at least one compound of the invention in an effective amount to a pest's environment, including agricultural and / or non-agronomic invasion zones, directly to the area to be protected or to the pest to be controlled. Pests are controlled. Accordingly, the present invention relates to an invertebrate or an environment thereof in a biologically effective amount of at least one compound of the present invention, or a composition comprising at least one such compound or at least one such compound and at least one additional biologically active compound or agent effective amount. A method of controlling invertebrate in agronomic and / or nonagronomic applications, including contacting the comprising composition, is further included. Examples of suitable compositions comprising a compound of the invention and at least one additional biologically active compound or agent effective amount are such that the additional biologically active compound is on the same granule as the compound of the invention or on a granule separate from the compound of the invention It comprises a granule composition.

Preferred contact method is spraying. Alternatively, granular compositions comprising a compound of the present invention may be applied to plant foliar or soil. In addition, the compounds of the present invention may be prepared through the plant uptake by contacting the plant with a composition comprising the compound of the invention applied as a soil drunk of a liquid formulation, a granule formulation into the soil, a seedling box treatment or a immersion of an implant. Delivered effectively. The compound is also effective to topically apply a composition comprising a compound of the invention to the invasion zone. Other contact methods include direct and residual spraying, air spraying, gel, seed coating, microencapsulation, permeable absorption, bait, eartag, bolus, smoker, fumigant, aerosol, powder, etc. Application of the compounds or compositions of the invention. The compounds of the present invention may also be dipped in materials for making invertebrate control devices (eg insect nets).

The compounds of the present invention may be incorporated into bait compositions that are consumed by invertebrate pests or used in devices such as traps, bait stations, and the like. Such bait compositions may comprise (a) an active ingredient, i.e. a compound of Formula 1, an N-oxide or salt thereof, (b) one or more food substances, (c) optionally attractants, and (d) optionally one or more wetting agents. It may be in the form of granules comprising. Importantly, about 0.001 to 5% active ingredient; Food material and / or attractant about 40-99%; And optionally a granule or bait composition comprising about 0.05 to 10% wetting agent is effective at controlling soil invertebrate pests at very low application rates, especially at doses of the deadly active ingredient by ingestion rather than by direct contact. Importantly, the food substance will function as both a food source and an attractant. Food substances include carbohydrates, proteins and fats. Examples of food substances are vegetable flours, sugars, starches, animal fats, vegetable oils, yeast extracts and milk solids. Examples of attractants are exploitation and flavoring agents, such as fruit or plant extracts, flavors, or other agents known to attract pests of other animal or plant components, pheromones or target invertebrates. Examples of humectants, ie moisture retainers, are glycols and other polyols, glycerin and sorbitol. Of particular interest are bait compositions (and methods of using such bait compositions) used to control invertebrate pests, including ants, termites, and cockroaches individually or in combination. An apparatus for controlling invertebrate pests may include a bait composition of the invention and a mold adapted to receive the bait composition, the mold having one or more openings of a size that allows the invertebrate pest to pass through the invertebrate Animal pests may access the bait composition from an outside location of the mold, which is further adapted to be located at or near a potential or known place of activity for invertebrate pests.

The compounds of the present invention may be applied in neat state, but most often they will be applied as a preparation comprising one or more compounds together with a suitable carrier, diluent and surfactant and possibly with food according to the intended end use. Preferred application methods include spraying an aqueous product or a refined oil solution of the compound. Spray oil, spray oil concentrate, spreader sticker, adjuvant, other solvents and mixtures with synergists such as piperonyl butoxide often enhance compound efficacy. For non-agricultural applications such spraying may be applied by ejecting from a spray container, such as a can, bottle or other container, by a pump or from a pressurized container (eg a pressurized aerosol spray can). Such spray compositions may take various forms such as, for example, sprays, mists, foams, mists or fog. Such spray compositions may optionally further comprise propellants, blowing agents, and the like. Of importance is a spray composition comprising a compound or composition of the invention and a propellant. Representative propellants include methane, ethane, propane, isopropane, butane, isobutane, butene, pentane, isopentane, neopentane, pentene, hydrofluorocarbons, chlorofluoroacarbons, dimethyl ethers, and mixtures thereof It is not limited to this. Importantly, spray compositions used to control invertebrate pests, including individually or in combination, mosquitoes, black flies, chimpanzees, stag flies, horse flies, wasps, yellow wasps, bumblebees, ticks, spiders, ants, hornbills, etc. (And how to use such a spray composition dispensed from a spray container).

The rate of application (ie, "biologically effective amount") required for effective control depends on the species of invertebrate being controlled, the life cycle of the pest, life stage, size, place of habitat, year-round time, host crop or animal, feeding habits, mating habits, surroundings. It will depend on factors such as humidity, temperature, etc. Under normal circumstances, an application rate of about 0.01 to 2 kg of active ingredient per hectare is sufficient to control pests in agricultural ecosystems, but may be sufficient as 0.0001 kg / ha or may require as much as 8 kg / ha. Effective rates for non-agricultural applications range from about 1.0 to 50 mg / square meter, but 0.1 mg / square meter may be sufficient, or 150 mg / square meter may be required. One skilled in the art can readily determine the biologically effective amount necessary for the desired level of invertebrate pest control.

The following tests demonstrate the control efficacy of certain compounds of the invention against pests. "Control efficacy" refers to the inhibition (including lethal) of invertebrate pest growth leading to significantly reduced feeding. However, the pest control protection provided by the compounds is not limited only to these species. See Index Tables A, B and C for compound descriptions. The abbreviations used in the following index are as follows: i is iso, t is tertiary, Me is methyl, Et is ethyl, Pr is propyl, i -Pr is isopropyl, c -Pr is cyclopropyl, Bu is butyl , CN is cyano. The abbreviation “Ex.” Refers to the examples, and the number following “Ex” refers to the number of the example in which the compound was prepared.

Index table A

* Refer to Index Table C for ¹ H NMR data.

Index table B

Index table C

Biological Example of the Invention

Exam A

The test unit for evaluating the control of diamondback moth ( Plutella xylostella ) consisted of a small open container containing 12-14-day-radish plants inside. This was pre-infected with 10-15 newborn larvae on insect feed pieces by removing the plug from the cured insect feed sheet where many larvae grew on it using a core sampler and transferring the plug containing the larvae and feed to the test unit. I was. The larvae were transferred to the test plant when the feed plug was dry.

Test compounds were X-77® spreader low-form formula nonionic surfactants containing 10% acetone, 90% water, and alkylarylpolyoxyethylene, free fatty acids, glycols and isopropanol (Grillley, Colorado, USA). Formulated using a solution containing 300 ppm of Loveland Industries, Inc. The formulated compound was SUJ2 into a 1/8 JJ custom body (Spraying Systems Co., Wheaton, Ill.) Located 1.27 cm (0.5 inch) above the top of each test unit. It was applied with 1 ml of liquid through the nebulizer nozzle. All experimental compounds in this test were sprayed at 50 ppm and this was repeated three times. After spraying the formulated test compounds, each test unit was dried for 1 hour and then topped with a black screen cap. The test unit was maintained for 6 days in a growth chamber at 25 ° C. and 70% relative humidity. Plant feeding damage was then visually assessed based on the leaves consumed.

Of the compounds tested, the following compounds showed very good to good levels of plant protection (up to 20% feeding damage):

Exam B

The test unit for evaluating the control of the fall armyworm ( Spodoptera frugiperda ) consisted of a small open container containing 4-5-day-maize plants inside. It was pre-infected with 10-15 1-day-live larvae on insect feed pieces (using core sampler).

Test compounds were formulated as described for Test A and sprayed at 50 ppm. The application was repeated three times. After spraying, the test unit was visually evaluated after holding in the growth chamber as described for Test A.

Of the compounds tested, the following compounds showed good levels of plant protection (up to 20% feeding damage):

Exam C

In order to evaluate the control of green peach aphid ( Myzus persicae ) via contact and / or systemic methods, the test unit is a small open container with 12-15-day-live radish plants contained therein. It consisted of It was pre-infected (cut-leaf method) by placing 30 to 40 aphids on slices of leaves cut from the culture plants on the leaves of the test plants. The larvae were transferred to the test plants when the leaf pieces were dried. After pre-infection, the soil of the test unit was covered with a layer of sand.

The test compound is X-77® spreader low-form formula nonionic surfactant (Loveland Industries, Inc.) containing 10% acetone, 90% water, and alkylarylpolyoxyethylene, free fatty acids, glycols and isopropanol. Formulated using a solution containing 300 ppm. The formulated compound was applied as 1 ml of liquid through a SUJ2 nebulizer nozzle with a 1/8 JJ Spraying Systems Co. located 1.27 cm (0.5 inch) above the top of each test unit. All experimental compounds on this screen were sprayed at 250 ppm and this was repeated three times. After spraying the formulated test compounds, each test unit was dried for 1 hour and then topped with a black screen cap. The test unit was held for 6 days in a growth chamber at 19-21 ° C. and 50-70% relative humidity. Each test unit was then visually assessed for mortality of the insect.

Of the compounds tested, the following compounds exhibited a mortality of at least 80%:

Test D

In order to evaluate the control of potato leafhopper ( Empoasca fabae Harris) via contact and / or permeability methods, the test unit was a 5-6 day-long Longio bean plant (primary leaves). Consists of a small open container inside. White sand was added to the top of the soil and one of the primary leaves was cut before application. Test compounds were formulated as described in Test C and sprayed at 250 ppm and repeated three times. After spraying, the test unit was allowed to dry for 1 hour and then post infected with 5 potato larvae (18-21 days old adult). A black screen cap was placed on top of the cylinder. The test unit was held for 6 days in a growth chamber at 19-21 ° C. and 50-70% relative humidity. Each test unit was then visually assessed for mortality of the insect.

Of the compounds tested, the following compounds exhibited a mortality of at least 80%:

Test E

To evaluate the control of cotton melon aphid (Aphis gossypii ) via contact and / or permeable methods, the test unit consisted of a small open container with 6-7-day-live cotton plants contained therein. . It was pre-infected with 30-40 insects on the leaf slices according to the cut-leaf method described for Test C and the soil of the test unit was covered with a layer of sand.

Test compounds were formulated and sprayed at 250 ppm as described for Test D. Application was repeated three times. After spraying, the test unit was maintained in the growth chamber as described in Test D and then visually evaluated.

Of the compounds tested, the following compounds exhibited a mortality of at least 80%:

Exam F

In order to evaluate the control of corn planthoppers ( Peregrinus maidis ) through contact and / or permeability methods, the test unit consists of small open containers containing 3-4 lifetime maize plants (ears) inside. It became. White sand was added to the top of the soil before application. As described in Test C, test compounds were formulated, sprayed at 25 ppm and repeated three times. After spraying, the test unit was dried for 1 hour and then post-infected with 10-20 cornstarches (18-20 day larvae) by sprinkling on sand using a salt shaker. A black screen cap was placed on top of the cylinder. The test unit was held for 6 days in a growth chamber at 19-21 ° C. and 50-70% relative humidity. Each test unit was then visually assessed for mortality of the insect.

Of the compounds tested, the following compounds exhibited a mortality of at least 80%:

Test G

To evaluate the control of silverleaf whitefly ( Bemisia tabaci ), the test unit was grown on Redi- earth® Scotts Co. and two or more true leaves It consisted of 14-21 lifetime cotton plants infected with second and third larvae on the back of the leaves.

Test compounds were formulated with up to 2 mL of acetone and then diluted to 25-30 mL with water. The formulated compound was applied using a flat fan air-aid nozzle (Spraying Systems 122440) at 10 psi (69 kPa). The plants were sprayed to flow on a turntable injector. In this screen all experimental compounds were sprayed at 250 ppm, which was repeated three times. After spraying the test compounds, the test units were held in the growth chamber for 6 days at a relative humidity of 50-60% and a temperature of 28 ° C. during the day and 24 ° C. at night. The leaves were then removed and the dead and fleshy larvae counted to calculate the percent lethality.

Of the compounds tested, the following compounds exhibited a mortality of at least 80%:

Test H

In order to evaluate the control of green peach aphids ( Myzus persicae ) and potato cicada ( Empoasca fabae ) after the movement of compounds in plants and the leaf movement of compounds through the plants, the test unit was a 12-15-day-live radish plant (green peach It consists of a small open container containing either aphid test) or 5-6 day freshonio bean plants (for potato cicada test).

The test compound was X-77® spreader low-form formula nonionic surfactant (Loveland Industries, Inc.) containing 10% acetone, 90% water, and alkylarylpolyoxyethylene, free fatty acids, glycols and isopropanol. Formulated using a solution containing 600 ppm. The formulated compound was applied 20 microliters by pipette to two larger photosynthetically active leaves. In this screen all experimental compounds were applied at 1000 ppm and the test was repeated three times. After applying the formulated test compounds, the soil of each test unit was covered with a layer of sand and each test unit was allowed to dry for 1 hour, followed by a black screen cap. The test unit was maintained in a growth chamber at about 20 ° C. and 50-70% relative humidity.

After 2 days, all sides of the treated leaves were covered with a fine plastic net but the leaf tip remained still attached to the leaves to allow normal vasculature and photosynthesis. The plants were then infected with 20 to 30 aphids (or radish) or 20 cicada (beans) and maintained for 8 more days in the growth chamber. Each test unit was visually assessed for mortality of insects fed by contacting untreated plant tissue.

The results of green peach aphid mortality (% GPA M) and potato cicada mortality (% PLH M) are listed in Table A.

Table A

Exam I

In order to assess the control of green peach aphids ( Myzus persicae ) and potato cicada ( Empoasca fabae ) after the movement of the compounds in the plants and the woody transfer of the compounds from the soil application to the leaves through the roots, the test unit was 12-15-day- It consisted of small open containers containing either green radish plants (for testing green peach aphids) or 5-6 day fresh rongio bean plants (for testing potato cicada).

The test compound was X-77® spreader low-form formula nonionic surfactant (Loveland Industries, Inc.) containing 10% acetone, 90% water, and alkylarylpolyoxyethylene, free fatty acids, glycols and isopropanol. Formulated using a solution containing 600 ppm. The formulated compound was applied in a 1 mL solution by pipetting into the soil at the base of the plant. In this screen all experimental compounds were applied at 1000 ppm and the test was repeated three times. After application of the formulated test compounds, each test unit was allowed to dry for 1 hour. The soil of each test unit was covered with a layer of sand, then a black screen cap was placed on top. The test unit was maintained in a growth chamber at about 20 ° C. and 50-70% relative humidity.

After 2 days, the plants were infected with 20 to 30 aphids (no radish) or 20 cicada larvae (soybeans) and maintained for 5 more days in the growth chamber. Each test unit was visually assessed for lethality of insects fed by contact on untreated plant leaves.

The results of green peach aphid mortality (% GPA M) and potato cicada mortality (% PLH M) are listed in Table B.

TABLE B

Claims (16)

A compound of formula I, N-oxide or salt thereof. <Formula I> Where R ¹ is Me, Cl, Br or F; R ² is F, Cl, Br, C ₁ -C ₄ haloalkyl or C ₁ -C ₄ haloalkoxy; R ³ is F, Cl or Br; R ⁴ is H; C ₁ -C ₄ alkyl, C ₃ -C ₄ alkenyl, C optionally substituted with one substituent selected from the group consisting of halogen, CN, SMe, S (O) Me, S (O) ₂ Me, and OMe, respectively ₃ -C ₄ alkynyl, C ₃ -C ₅ cycloalkyl, or C ₄ -C ₆ cycloalkylalkyl; R ⁵ is H or Me; R ⁶ is H, F or Cl; R ⁷ is H, F or Cl. The method of claim 1, R ¹ is Me or Cl; R ² is Cl, Br, CF ₃ , OCF ₂ H, OCF ₃ or OCH ₂ CF ₃ ; R ⁴ is H, Me, Et, i-Pr, t-Bu, CH ₂ CN, CH (Me) CH ₂ SMe or C (Me) ₂ CH ₂ SMe. The method of claim 2, R ² is Cl, Br, CF ₃ or OCH ₂ CF ₃ ; R ⁴ is H, Me, Et or i-Pr, R ⁵ is H. An invertebrate pest comprising a biologically effective amount of the compound of claim 1 and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, and optionally further comprising an effective amount of one or more additional biologically active compounds or agents. Composition for controlling. The method of claim 4, wherein the one or more additional biologically active compounds or agents are pyrethroids, carbamates, neonicotinoids, neurosodium channel blockers, insecticidal macrocyclic lactones, γ-aminobutyric acid (GABA) antagonists, bactericides The composition is selected from the group of insecticides of the group consisting of loyal urea, larval hormone mimetics, members of Bacillus thuringiensis , Bacillus thuringiensis delta endotoxin, and naturally occurring or genetically modified viral insecticides. The method of claim 4, wherein the one or more additional biologically active compounds or agents are abamectin, acetate, acetamiprid, acetoprole, amidoflumet (S-1955), avermectin, azadilactin, azinfos- Methyl, bifenthrin, bifenazate, bistrifluron, buprofezin, carbofuran, chlorfenapyr, chlorfluazuron, chlorpyrifoss, chlorpyrifos-methyl, chromafenozide, clotiani Dean, cyfluthrin, beta-cifluthrin, sihalothrin, lambda-sihalothrin, cipermethrin, cyromazine, deltamethrin, diafenthiuron, diazinone, diflubenzuron, dimethate, dino Tefuran, diophenolran, emamectin, endosulfan, esfenvalerate, ethyprolol, phenoticarb, phenoxycarb, phenpropatrine, fenvalrate, fipronil, phlonicamide, flucitrinate , Tau-Fluvalinate, Flufenerim (UR-50701), Flupe Nocturne theory, gamma-chalotrine, halofenozide, hexaflumuron, imidacloprid, indoxacarb, isofenfos, lufenuron, malathion, metaldehyde, metamidophos, methadide, metomile, Metoprene, Methoxycyclo, Methoxyphenozide, Metofluthrin, Monoclotophos, Methoxyphenozide, Novaluron, Nobiflumuron (XDE-007), Oxamyl, Parathion, Parathion-methyl , Permethrin, forate, posalon, phosmet, phosphamidone, pyrimcarb, propenophos, propfluthrin, protrifenbut, pymetrozine, pyridalyl, pyriproxyfen, rotenone, S1812 ( Valent) Spinosad, spiromesifen (BSN 2060), Sulprofos, tebufenozide, teflubenzuron, tefluthrin, terbufoss, tetrachlorbinfos, tiacloprid, thiamethoxam, thiodica Lev, thiosulfato-sodium, tolfenpyrad, tralomethrin, trichlorphone and tripleru Lone, aldicarb, phenamifos, amitraz, chinomethionate, chlorobenzylate, cyhexatin, dicopol, dienochlor, ethoxazole, phenazaquine, fenbutatin oxide, fenpyroximate , Hexia tribes, propargite, pyridaben, tebufenpyrad, Bacillus thuringiensis aizawai , Bacillus thuringiensis kurstaki , Bacillus thuringiensis delta endotoxin, baculovirus (baculovirus), entomopathogenic bacteria, entomopathogenic viruses and entomopathogenic fungi. The method of claim 4, wherein the one or more additional biologically active compounds or agents are acetamiprid, cipermethrin, sihalothrin, cifluthrin and beta-cifluthrin, espenvalrate, penvallarate, tralomethrin , Phenoticcarb, metomil, oxamyl, thiodicarb, clothianidine, imidacloprid, thiacloprid, indoxacarb, spinosad, abamectin, avermectin, emamtine, endosulfan, etiprol, Fipronil, flufenoxuron, triflumuron, diophenolran, pyriproxyfen, pimetrozine, amitraz, Bacillus thuringiensis aisawa, Bacillus thuringiensis kurstaki, Bacillus thuringiensis delta endotoxin and insect pathogenicity The composition is selected from the group consisting of fungi. A method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of the compound of claim 1. A method of controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of the composition of claim 4. 10. The method of claim 8 or 9, wherein the invertebrate pest is a cockroach, ant or termite contacted by the compound by consuming a bait composition comprising the compound. 10. The mosquito, black fly, stable fly and deer fly of claim 8 or 9, wherein the invertebrate pest is contacted by a spray composition comprising the compound dispensed from the spray container. fly, horse fly, wasp, yellow jacket, bumblebee, tick, spider, ant, gnat. (a) the compound of claim 1; And (b) propellants Injection composition comprising a. (a) the compound of claim 1; (b) one or more food substances; (c) optionally attractant; And (d) optionally a humectant Bait composition comprising a. (a) the bait composition of claim 13; And (b) housing adapted to receive bait compositions Wherein the frame has one or more openings of a size that allows the invertebrate pest to pass through the opening, thereby allowing the invertebrate pest to access the bait composition from a location outside the frame and against the invertebrate pest A device for controlling invertebrate pests, further adapted to be located at or near a potential or known activity site. 10. The method of claim 9, wherein the plant is contacted with a composition applied as a soil trench of the liquid formulation. The composition of claim 4 in the form of a soil trench liquid formulation.