AU8414691A - Herbicidal substituted aryl alkylsulfonyl pyrazoles - Google Patents

Description

HERBICIDAL SUBSTITUTED ARYL ALKYLSULFONYL PYRAZOLES

FIELD OF THE INVENTION

The field of the invention contemplated herein pertains to herbicidal compounds generically defined by the above title, to compositions containing same and processes for preparing said compounds.

BACKGROUND OF THE INVENTION

Various substituted 3- and 5-arylpyrazole-type compounds are known in the literature. Such compounds have various utilities, e.g., as chemical intermediates, pharmaceuticals and herbicides.

Among the substituted-arylpyrazole compounds in the prior art are those having a variety of substituent radicals on the aryl and/or pyrazole moieties of the compound. For example, compounds of this type are known wherein the aryl moeity is a substituted or unsubstituted phenyl radical, in which the substituent radicals are alkyl, cycloalkyl, alkaryl, halogen, trifluoromethyl, heterocyclic or substituted hetero- cyclic, e.g., thienyl or alkyl-substituted furanyl, pyridyl, pyrimidinylurea, etc. and the pyrazolyl radical is substituted in various positions on the N or carbon atoms with alkyl, halogen, alkoxy, heterocycles, S(O)_nR members, wherein n is 0-2 and R may be a variety of radicals such as those substituted on the aryl or pyrazole moieties.

Prior compounds of the above type having utility as herbicides, typically require application rates as high as five or ten or more kilograms per hectare to achieve adequate weed control. Accordingly, it is an object of this invention to provide a novel class of arylpyrazole-type compounds having uniquely high phytotoxic unit activity against a spectrum of weeds, including narrovleaf and broadleaf weeds yet maintain a high degree of safety in a plurality of crops, especially small grains and/or row crops such as wheat, barley, corn, soybeans, peanuts, etc. SUMMARY OF THE INVENTION

This invention relates to herbicidally-active compounds, compositions containing these compounds, processes for making them and herbicidal methods of using same

wherein

R₁ is hydrogen, C_1-5 alkyl optionally substituted with an R₄ member; C_3-8 cycloalkyl or cycloalkenyl optionally substituted with C_1-4 alkyl;

R₂ is C_1-5 alkyl optionally substituted with an R₄ member;

R₃ is hydrogen or halogen and

R₄ is hydrogen, C_1-8 alkyl, haloalkyl, alkyl- thio, alkoxyalkyl or polyalkoxyalkyl, C_3-8 cycloalkyl, cycloalkenyl, eyeloaIkyalkyl or cycloalkenylalkyl; C_2-8 alkenyl or alkynyl; carbamyl, halogen, amino, nitro, cyano, hydroxy, C_4-10 heterocycle containing 1-4 O, S(O)_m and/or N hetero atoms, C_6-12 aryl, aralkyl or alkaryl, -CXYR₈, -CXR₉, -CH₂OCOR₁₀, -YR₁₁, -NR₁₂R₁₃, or any two R₄ members may be combined through a saturated and/or unsaturated carbon, and/or hetero atom linkage to form a heterocyclic ring having up to 9 ring members, which may be substituted with any of said R₄ members or where not self-inclusive said R₄ or R_8-13 members substituted with any of said R₄ members; provided that when said two R₄ members are combined through a -hetero atom - linkage, said heterocyclic ring has at least six ring members;

X is O, S(O)_m, NR₁₄ or CR₁₅R₁₆;

Y is O or S(O)_m or NR₁₇;

R₈-R₁₇ are one of said R₄ members; m is 0-2 and

n is 0-5.

A preferred subgenus of substituted-arylpyrazolyl compounds in this invention are those according to Formula II

wherein

R₁, R₂ and R₃ are as defined for Formula I;

R₅ is independently one of said R₃ members and

R₆ and R₇ are independently one of said R₄ members or are combined to form a heterocyclic ring having up to 9 members and containing O, N and/or S atoms, which ring may be substituted with alkyl, haloalkyl, alkoxy, alkenyl or alkynyl radicals each having up to 4 carbon atoms; provided that when said two R₆ and R₇ members are combined through a -hetero atom linkage, said heterocyclic ring has at least six ring members.

Particularly preferred compounds of this invention are those according to Formula III

wherein

R₁ and R₂ are C_1-5 alkyl;

R₃ and R₅ are hydrogen, bromo, chloro or fluoro; R₆ is an R₅ member or nitro;

R₇ is an R₄ member or

R₆ and R₇ are combined through an -OCH₂(C=O)- N-(R₄)-linkage to form a fused six-membered ring.

Still more preferred compounds according to

Formula III are those wherein

R₁ and R₂ are methyl;

R₃ is hydrogen, bromo or chloro;

R₅ is chloro or fluoro;

R₆ is chloro, fluoro or nitro;

R₇ is a YR₁₁ member as defined in Formula I or

R₆ and R₇ are combined through an -OCH₂(C=O)-N-(propynyl)-linkage to form a fused six-membered ring. Preferred species according to this invention include the following:

4-Chloro-3-(2-fluoro-4-chloro-5-(2-propynyloxy)phenyl)- 1-methyl-5-(methylsulfonyl)-1H-pyrazole

4-Bromo-3-(2-fluoro-4-chloro-5-(2-propynyloxy)phenyl)- 1-methyl-5-(methylsulfonyl)-1H-pyrazole

4-Chloro-3-(2-fluoro-4-chloro-5-(2-methoxyethoxy)- phenyl) -1-methyl-5- (methylsulfonyl) -1H-pyrazole 4-Bromo-3-(2-fluoro-4-chloro-5-(2-methoxyethoxy)- phenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole 6- (4-Chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3- yl)-7-fluoro-4-(2-propynyl)-2H-l,4-benzoxazin-3- (4H)-one

(5-(4-Bromo-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3- yl)-2-chloro-4-fluorophenoxy) acetic acid, 1- methylethyl ester

(5-(4-Chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3- yl)-2-chloro-4-fluorophenoxy) acetic acid, 1- methylethyl ester

2-(5-(4-Bromo-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3- yl)-2-chloro-4-fluorophenoxy)propanoic acid, ethyl ester and 2-(5-(4-Chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol- 3-yl)-2-chloro-4-fluorophenoxy)propanoic acid, ethyl ester.

Another aspect of this invention relates to processes for preparing the compounds according to

Formulae I-III and their precursors and intermediates starting materials. These process aspects will be discussed in more detail below.

Other aspects of this invention relate to herbicidal compositions containing the compounds of

Formulae I-III and to herbicidal methods of using those compositions to control undesirable weeds.

It is further within the purview of this invention that the substituted-arylpyrazole compounds of Formulae I-III be formulated in compositions containing other herbicidal compounds as co-herbicides, e.g., acetanilides, thiocarbamates, ureas, sulfonylureas, imidazolinones, benzoic acids and their derivatives, diphenyl ethers, salts of glyphosate, etc.

Other additaments may be included in such herbicidal formulations as desired and appropriate, e.g., antidotes (safeners) for the herbicide(s), plant disease control agents, such as fungicides, insecticides, nematicides and other pesticides.

As used herein, the terms "alkyl", "alkenyl", alkynyl" when used either alone or in compound form, e.g., haloalkyl, haloalkenyl, alkoxy, alkoxyalkyl, etc., are intended to embrace linear or branched-chain

members. Preferred alkyl members are the lover alkyls having from 1 to 4 carbon atoms and preferred alkenyl and alkynyl members are those having from 2 to 4 carbon atoms.

The term "haloalkyl" is intended to mean alkyl radicals substituted with one or more halogen (chloro, bromo, iodo or fluoro) atoms; preferred members of this class are those having from 1 to 4 carbon atoms, especially the halomethyl radicals, e.g., trifluoro methyl. In polyhaloalkyl members, the halogens can all be the same or mixed halogens.

Representative, non-limiting alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl and cycloalkenylalkyl members include the following:

Methyl, ethyl, the isomeric propyls, butyls, pentyls, hexyls, heptyls, octyls, nonyls, decyls, etc.; vinyl, allyl, crotyl, methallyl, the isomeric butenyls, pentyls, hexenyls, heptenyls, octenyls; ethynyl, the isomeric propynyls, butynyls, pentynyls, hexynyls, etc.; the alkoxy, polyalkoxy, alkoxyalkyl and polyalkoxyalkyl analogs of the foregoing alkyl groups, e.g., methoxy, ethoxy, propoxys, butoxys, pentoxys and hexoxys and corresponding polyalkoxys and alkoxyalkyls, e.g., methoxymethoxy, methoxyethoxy, ethoxymethoxy, ethoxyethoxy, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, propoxymethyl, isopropoxymethyl, butoxymethyl, isobutoxymethyl, tertbutoxymethyl, pentoxymethyl, hexoxymethyl, etc., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, etc.; the isomeric cyclopentenes, cyclohexenes and cycloheptenes having mono-or di-unsaturation; representative aryl, aralkyl and alkaryl groups include phenyl, the isomeric tolyls and xylyls, benzyl, naphthyl, etc.

Representative mon-, di- and tri- haloalkyl members include: chloromethyl, chloroethyl, bromomethyl, bromoethyl, iodomethyl, iodoethyl, chloropropyl, bromopropyl, iodopropyl, 1,1-dichloromethyl, 1,1-dibromomethyl, 1,1-dichloropropyl, 1,2-dibromopropyl, 2,3-dibromopropyl, 1-chloro-2-bromoethyl, 2-chloro-3- bromopropyl, trifluoromethyl, trichloromethyl, etc.

Representative heterocyclic members include: alkylthiodiazolyl; piperidyl; piperidylalkyl; dioxolanylalkyl, thiazolyl; alkylthiazolyl; benzothiazolyl; halobenzothiazolyl; furyl; alkyl-substituted furyl;

furylalkyl; pyridyl; alkylpyridyl; alkyloxazolyl;

tetrahydrofurylalkyl; 3-cyanothienyl; thienylalkyl; alkyl-substituted thienyl; 4,5-polyalkylene-thienyl;

piperidinyl; alkylpiperidinyl; pyridyl; di- or

tetrahydropyridinyl; alkyltetrahydromorpholyl;

alkylmorpholyl; azabicyclononyl; diazacycloalkanyl, benzoalkylpyrrolidinyl; oxazolidinyl; perhydrooxazolidinyl; alkyloxazolidyl; furyloxazolidinyl, thienyloxazolidinyl, pyridyloxazolidinyl, pyrimidinyloxazolidinyl, benzooxazolidinyl, C_3-7 spirocycloalkyloxazolidinyl, alkylaminoalkenyl; alkylideneimino; pyrrolidinyl; piperidonyl; perhydroazepinyl; perhydroazocinyl; pyrazolyl; dihydropyrazolyl; piperazinyl; perhydro-l,4-diazepinyl; quinolinyl, isoguinolinyl; di-, tetra- and perhydroquinolyl - or - isoquinolyl; indolyl and di- and perhydroindolyl and said heterocyclic members substituted with radicals such as the members defined in Formula I.

As used herein, the term "agriculturallyacceptable salts" (of the compounds defined by the above formulae) is meant a salt or salts which readily ionize in aqueous media to form a cation or anion of said compounds and the corresponding salt anion or cation, which salts have no deleterious effect on the herbicidal properties of a given herbicide and which permit formulation of the herbicide composition without undue problems of mixing, suspension, stability, applicator equipment use, packaging, etc.

By "herbicidally-effective" is meant the amount of herbicide required to effect a meaningful injury or destruction to a significant portion of affected undesirable plants or weeds. Although of no hard and fast rule, it is desirable from a commercial viewpoint that 80-85% or more of the weeds be destroyed, although commercially significant suppression of weed growth can occur at much lover levels, particularly with some very noxious, herbicide-resistant plants. DETAILED DESCRIPTION OF THE INVENTION

The compounds according to this invention are suitably prepared by a variety of processes as will be described below.

In broad aspect, the preferred overall process for preparing the compounds of Formulae I-III is best viewed in the separate process steps required to get the necessary intermediates, immediate precursors and end products of the above formulae. Viewed from this perspective, there are at least thirteen main process steps involved and these will be described below. The products according to Formulae I-III are prepared by the general "Processes I-XIII" scheme described below; it being expressly understood that various modification obvious to those skilled in the art are contemplated. Specific embodiments are described in Examples 1-27 below.

In the sequence of process steps described below, the various symbols defining radical substituents, e.g., R₁-R₁₇, X, Y, etc. have the same meanings as defined for the compounds of Formulae I-III, unless otherwise qualified or limited.

PROCESS I

This process describes the preparation of important intermediate compounds, which are useful in the overall process scheme for producing compounds of Formulae I-III. Such intermediate compounds of Formula B belov in which R₃ is H are prepared by this process step.

The process for the preparation of compounds according to Formula B suitably proceeds from (un) substituted acetophenones of Formula A which are known in the art. The process can be carried out in any anhydrous solvent or mixture of such solvents; the preferred solvents are dimethylsulfoxide, toluene, benzene, etc. The (un) substituted acetophenones are treated with a strong base such as an alkali hydride or alkali alkoxide with alkali alkoxides such as potassium t-butoxide being preferred. The basic mixture is treated with carbon disulfide. Reaction temperature is in the range of -100ºC to 100ºC, preferably -78ºC to 50ºC. After addition of the carbon disulfide is complete, the reaction may be treated with an alkylhalide,

alkyldihalide, alkylsulfate, dialkylsulfonate or other suitable alkylating agent with the preferred reagent being methyl iodide. The reaction period may be chosen from the range of a few minutes to several weeks

depending on the amounts of reagents, reaction temperature, etc. After completion of the reaction the

intermediate 1-(substituted)-3,3-bis(alkylthio)-2-propen-1-one is isolated by diluting the reaction mixture with water and the product is isolated by a method such as crystallization or solvent extraction. If necessary, the product is purified by standard methods. The cyclization of this intermediate to give compounds of Formula B can be carried out in any

suitable solvent by treatment with hydrazine or

substituted hydrasines with alkylhydrazines being preferred. Reaction temperature is in the range of

-78ºC to 150ºC, preferably 10ºC to 100ºC. The reaction period may be chosen from the range of a few minutes to several weeks depending on the amounts of reagents, reaction temperature, etc. The product is isolated after completion of the reaction by filtration and/or concentration of the reaction mixture. If necessary, the product is purified by standard methods such as extraction, crystallization, column chromatography, etc. In the case of the addition of hydrazine to the intermediate 1-(substituted)-3,3-bis(alkylthio)-2-propen-1-one, the resultant pyrazole may be treated with an alkyl halide, alkyl sulfonate or other suitable alkylating agent to obtain compounds of Formula B. In this case, products of Formula B can be obtained by treatment of the above compound with an alkylating agent such as methyl iodide, benzyl bromide, allyl bromide, dimethyl sulfate, etc. The preferred solvents are dimethylsulfoxide, acetone, dimethylformamide, dioxane, etc. Reaction temperature is in the range of -78ºC to 150ºC, preferably 10ºC to 100ºC. The reaction period may be chosen from the range of a few minutes to several weeks depending on the amounts of reagents, reaction temperature, etc. The product is isolated after completion of the reaction by filtration and/or concentration of the reaction mixture. If necessary, the product is purified by standard methods such as

extraction, crystallization, column chromatography, etc.

The 2-fluoro-4-chloro-5-methoxyacetophenone, used to prepare compound Nos. 4, 9, 10 and 11 in Table 1 by the above process, was prepared from 2-chloro-4-fluoroanisole, which can be obtained from 2-chloro-4-fluoro-phenol by methods known in the art (C. A. Buehler and D. E. Pearson, Survey of Organic Synthesis, pp. 285- 382, Wiley-Interscience, New York, 1970). Treatment of 2- chloro-4-fluoroanisole with titanium tetrachloride and dichloromethylmethylether at room temperature gives 2- fluoro-4-chloro-5-methoxybenzaldehyde. The 2-fluoro- 4-chloro-5-methoxybenzaldehyde is converted to 2-fluoro- 4-chloro-5-methoxyacetophenone by treatment with methyl Grignard folloved by oxidation using standard methods known in the art.

The above mentioned 2-fluoro-4-chloro-5- methoxyacetophenone and its analogous precursor, 2- fluoro-4-chloro-5-methoxybenzaldehyde and processes for preparing them are the discovery of other inventors (Bruce C. Hamper and Kindrick L. Leschinsky) employed by the assignee herein.

Table 1 shovs typical examples of compounds prepared by Process I.

Compounds such as those Formula B species shown in Table I are useful as starting materials to prepare various other compounds which, in turn, are useful as intermediates in the preparation of compounds according to Formula II. For example, the compounds in Table I may be halogenated at the pyrazole 3-position to prepare novel compounds typified by those shown in Table

II .

This process describes an important step involving oxidation of compounds according to Formula B to prepare compounds according to Formula I. The important feature of this process step is the conversion of sulfide derivatives of Formula B to obtain the S,S- dioxide derivatives of Formula I compounds. Accordingly, it will be understood that the oxidation system described below is merely representative, but conceptually any suitable means of accomplishing the intended conversion of sulfide derivatives of Formula B to S,S- dioxide derivatives of Formula I is contemplated herein.

Oxidation of substituted thiopyrazoles of Formula B can give the corresponding sulfonylpyrazoles of Formula I. Any inert solvent may be used in this reaction that does not markedly hinder the reaction from proceeding. Such solvents include, but are not limited to, organic acids, inorganic acids, hydrocarbons, halogenated hydrocarbons, aromatic hydrocarbons, ethers or sulfones. Suitable oxidants include, but are not limited to molecular oxygen, organic and inorganic peroxides, organic peracids, inorganic oxides; the preferred reagents being hydrogen peroxide, perbenzoic acids, alkali periodates, alkali permanganates, etc. Reaction temperature is in the range of -78ºC to 150ºC, preferably 10ºC to 100ºC. The reaction period may be chosen from the range of a few minutes to several weeks depending on the amounts of reagents, reaction

temperature, etc. After completion of the reaction the product is isolated by diluting the reaction mixture with water and the product is isolated by a method such as crystallization or solvent extraction. If necessary, the product is purified by standard methods.

PROCESS III

In this process description, one class of products according to Formula D wherein R₃ is halogen is prepared by the halogenation of the corresponding

Formula C compound wherein R₃ is hydrogen and p is 0 or 2.

Any inert solvent may be used in this reaction that does not markedly hinder the reaction from proceeding. Such solvents include, but are not limited to, organic acids, inorganic acids, hydrocarbons, halogenated hydrocarbons, aromatic hydrocarbons, ethers and sulfides, sulfoxides or sulfones. Halogenating agents suitable for the above reaction include bromine,

chlorine, N-bromosuccinimide, N-chlorosuccinimide, sulfuryl chloride, 1,3-dichloro-5,5-dimethylhydantoin, etc. With some halogenating agents it is preferable to use an organic peroxide or light as a catalyst. The amount of halogenating agent can range from equivalent molar amounts to an excess. Reaction temperature is in the range of -100ºC to 150ºC, preferably 10ºC to 100ºC. The reaction period may be chosen from the range of a few minutes to several weeks or longer depending on the amounts of reagents, reaction temperature, etc. After completion of the reaction the product is isolated by diluting the reaction mixture with water and the product is isolated by a method such as crystallization or solvent extraction. If necessary, the product is purified by standard methods. PROCESS IV

This section describes a process for the preparation of compounds according to Formula I in which one of the R₄ residues is a nitro group (Formula E) starting with compounds according to Formula I.

Nitrating agents such as concentrated nitric acid, fuming nitric acid, mixtures of nitric acid with concentrated sulfuric acid, alkyl nitrates and acetyl nitrate are suitable for this reaction. Solvents such as mineral acids, organic solvents such as acetic anhydride or methylene chloride, and water or mixtures of these solvents may be used. The nitrating agent may be used in equimolar amounts or in excess. Reaction temperature is in the range of -100ºC to 150ºC, preferably -10ºC to 100ºC. The reaction period may be chosen from the range of a few minutes to several days depending on the amounts of reagents, reaction temperature, etc. After completion of the reaction the product is isolated by diluting the reaction mixture with water and the product is isolated by a method such as crystallization or solvent extraction. If necessary, the product is purified by standard methods.

PROCESS V

In this process description, one class of products according to Formula G (one species of Formula II compounds) is prepared by displacement of the Z radical of the corresponding compound of Formula F, wherein Z is any suitable leaving group of the

previously defined R₄ members.

SUBSTITUTE SHEET — , lo _Λ—

Formation of products of Formula G can be carried out by treatment of compounds of Formula F with an alkoxide, thioalkoxide, amine, etc., or an alcohol, mercaptan, amine, etc. in the presence of a base in any suitable solvent. The preferred solvents are dimethylsulfoxide, acetone, dimethylformamide, dioxane, water, etc. The base may be an organic base (such as a trialkylamine or another organic amine) or an inorganic base (an alkali carbonate such as potassium carbonate or sodium carbonate). Reaction temperature is in the range of -100ºC to 150ºC, preferably -10ºC to 100ºC. The reaction period may be chosen from the range of a few minutes to several weeks depending on the amounts of reagents, reaction temperature, etc. The product is isolated after completion of the reaction by filtration and/or concentration of the reaction mixture. If necessary, the product is purified by standard methods such as extraction, crystallization, column chromatography, etc.

PROCESS VI

In this process description, a variety of compounds of Formula I (exemplified by Formula J below are prepared from compounds of Formula H (Formula I compounds in which one of the R₄ members is a nitro residue).

A. In the first step of this two step process, compounds according to Formula H are reduced to give an amine derivative according to Formula J wherein one of the R4 radicals is an amine group. Reducing agents suitable in an acidic medium include, but are not limited to, metals such as iron, zinc or tin. The reaction solvent can include either organic or inorganic acids, such as acetic acid or hydrochloric acid, and may be used as concentrated acid solutions or dilute aqueous solutions. Reaction temperature is in the range of 0ºC to 150ºC, preferably 10ºC to 100ºC. The reaction period may be chosen from the range of a few minutes to several weeks depending on the amounts of reagents, reaction temperature, etc.

After completion of the reaction the product is isolated by diluting the reaction mixture with water and the product is isolated by a method such as crystallization or solvent extraction. If necessary, the product is purified by standard methods.

Alternatively, compounds of Formula H may be reduced by catalytic hydrogenation. For catalytic hydrogenation, which may be carried out at normal or elevated pressures, suitable catalysts include Raney nickel, palladium-carbon, palladium black, palladium on any suitable support, palladium oxide, platinum, platinum black, etc. Solvents include any inert solvent which does not markedly hinder the reaction including alcohols, ethers, etc. The product is isolated after completion of the reaction by filtration and concentration of the reaction mixture. If necessary, the product is purified by standard methods such as

extraction, crystallization, column chromatography, etc.

B. The amine radical of the product of step A can be converted to a variety of functional groups, e.g., a halogen (preferred), cyano, hydroxyl, etc., radical by the folloving step in the process. In this reaction any suitable solvent may be employed, although, anhydrous solvents such as anhydrous acetonitrile are preferred. A solution or slurry of the product of step A is treated with copper salts including cupric halides, cuprous halides, mixtures of cupric and cuprous halides or other copper salts and their mixtures and with an alkyl nitrite or other organic nitrites, such as t-butylnitrite. Reaction temperature is in the range of 0ºC to 150ºC, preferably 10ºC to 100ºC. The reaction period may be chosen from the range of a few minutes to several weeks depending on the amounts of reagents, reaction tempera- ture, etc. The product is isolated after completion of the reaction by filtration and/or

concentration of the reaction mixture. If necessary, the product is purified by standard methods such as extraction, crystallization, column chromatography, etc.

Alternative process operations for converting the amine radical to various functional groups,

including those mentioned in the preceding paragraph include use of various conventional procedures, e.g., the Sandmeyer, Meervein, etc., reactions which employ diazonium salts as intermediates.

PROCESS VII

In this process description, compounds according to Formula I, wherein one of the R₄ members is YH, are prepared from compounds according to Formula I wherein one of the R₄ members is YR₁₁ and R₁₁ is not hydrogen.

The reaction can be carried out as a solution or suspension in any suitable solvent or neat. A Levis acid such as, but not limited to, BBr₃, AlCl₃, etc. or inorganic acids such as concentrated or aqueous hydrochloric acid, sulfuric acid, hydrobromic acid, etc. can be employed. Reaction temperature is in the range of 0ºC to 150ºC, preferably 10ºC to 100ºC. The reaction period may be chosen from the range of a few minutes to several weeks depending on the amounts of reagents, reaction temperature, etc. The product is isolated after completion of the reaction by filtration and/or concentration of the reaction mixture. If necessary, the product is purified by standard methods such as extraction, crystallization, column chromatography, etc. PROCESS VIII

In this process description, compounds according to Formula I, wherein one of the R₄ members is YR₁₁ and R₁₁ is not hydrogen, are prepared from compounds according to Formula I wherein one of the R₄ members is YH.

In representative embodiments of this process, formation of products defined above can be carried out by treatment of the starting material with an alkylating agent such as an alkyl halide or alkyl sulfonate, e.g., methyl iodide, allyl bromide, propargyl bromide, methyl phenylsulfonate, etc., or an acylating agent. The reaction may be carried out in any suitable solvent or mixture of solvents, with or without a catalyst, in the presence or absence of a base. The preferred solvents are dimethylsulfoxide, acetone, dimethylformamide, dioxane, etc. The base may be an organic base (such as a trialkylamine or another organic amine) or an inorganic base (an alkali carbonate such as potassium carbonate or sodium carbonate). Reaction temperature is in the range of 0ºC to 150ºC. preferably 10ºC to 100ºC. The reaction period may be chosen from the range of a few minutes to several weeks depending on the amounts of reagents, reaction temperature, etc. the product is isolated after completion of the reaction by filtration and/or concentration of the reaction mixture. If necessary, the product is purified by standard methods such as extraction, crystallization, column chromatography, etc.

PROCESS IX

This process describes the preparation of compounds of Formula M (Formula II compounds wherein R₇ is YCH_2-n(R₁₈)_nCOYR₂₀) from the corresponding compounds of Formula K. The radicals R_18-20 are as previously defined for the said R₄ members.

A. In the first step of this two step process, compounds of Formula K are converted to compounds of

Formula L by hydrolysis of the YR₁₉ radical. The

reaction can be carried out in any suitable solvent or mixture of solvents, with or without a catalyst, in the presence of a base or acid. The preferred solvents are water, alcohols, dioxane, dimethylsulfoxide, acetone, dimethylformamide, etc. In the case of base hydrolysis, inorganic bases such as alkali hydroxides are preferred. For acid hydrolysis, inorganic acids such as concentrated hydrochloric acid or sulfuric acid, organic acids or mixtures of such acids may be employed. Reaction temperature is in the range of 0ºC to 150ºC, preferably 10ºC to 100ºC. The reaction period may be chosen from the range of a few minutes to several weeks depending on the amounts of reagents, reaction temperature, etc.

After completion of the reaction the product is isolated by diluting the reaction mixture with water and/or treating the solution with acid (in the case of base hydrolysis) and the product is isolated by a method such as crystallization or solvent extraction. If necessary the product is purified by standard methods.

B. The product of step A is converted to compounds of Formula M by esterification or an amide-forming reaction. This may be accomplished directly from compound L or via an alkali metal salt of compound L. The

esterification can be carried out by using an excess of the alcohol corresponding to the objective ester in the presence of a mineral acid (e.g., sulfuric acid). The amide derivatives can be prepared by treating compound L with the desired amine either neat or in a suitable solvent. The esterification or amide-forming reactions can also be carried out in the presence of an inert solvent and a dehydrating agent.

Alternatively, the product of step A can be converted to an acid halide or anhydride and treated with an alcohol or amine. Preparation of the acid halide is carried out in the presence of a halogenating agent such as, but not limited to, thionyl chloride, phosporus pentachloride, oxalyl chloride, etc., with or without an inert solvent. Any inert solvent which does not interfere with the reaction may be employed. A catalytic amount of an amine base such as triethylamine, pyridine or dimethylformamide or the like may be added for the purpose of promoting this reaction. The reaction temperature is in the range of -20ºC to the boiling point of the solvent used, the reaction period ranges from several minutes to 48 hours depending upon the amounts of reactants used and the reaction temperature. After completion of the reaction, the excess halogenating reagent and solvent(s) are removed from the reaction product by evaporation or distillation. The resultant acid halide may be subjected to an amine or alcohol directly or purified by the usual means. The acid halide is treated with an alcohol or amine to give a compound of Formula M. Any inert solvent may be employed and a catalytic amount of an amine base such as triethylamine, pyridine or dimethylformamide or the like may be added for the purpose of promoting this reaction. The reaction temperature is in the range of -20ºC to the boiling point of the solvent used. The reaction period ranges from several minutes to 48 hours depending upon the amounts of reactants used and the reaction temperature. The product is isolated after completion of the reaction by filtration and/or concentration of the reaction mixture. If necessary, the product is purified by standard methods such as extraction, crystallization, column chromatography, etc. PROCESS X

This process describes the preparation of compounds of Formulae O, P, Q, R, S or T (Formula II compounds in which the R₇ substituent is alkyl, substituted alkyl, haloalkyl, carboxaldehyde, carboxylic acid or a carboxylic acid derivative such as the previously defined CXYR₈ or CXR₉) from compounds of Formula N. The radicals R₂₁ and R₂₂ are as previously defined for the R₄ members and X₁ and X₂ are halogens. Process schematics are shown below.

In the first step of this process, compounds of Formulae N are converted to either compounds of

Formula O or Q or a mixture of these products. Any inert solvent may be used in this reaction that does not markedly hinder the reaction from proceeding. Such solvents include, but are not limited to, organic acids, inorganic acids, hydrocarbons, halogenated hydrocarbons, aromatic hydrocarbons, ethers and sulfides, sulfoxides or sulfones. Halogenating agents suitable for the above reaction include bromine, chlorine, N-bromosuccinimide, N-chlorosuccinimide, sulfuryl chloride, etc. With some halogenating agents it is preferable to use an organic peroxide or light as a catalyst. The amount of halogenating agent can range from an equal molar amount to an excess. Reaction temperature is in the range of

-100ºC to 150ºC, preferably 10ºC to 100ºC. The reaction period may be chosen from the range of a few minutes to several weeks depending on the amounts of reagents, reaction temperature, etc. After completion of the reaction the product or products are isolated by

diluting the reaction mix- ture with water and the product (s) are isolated by a method such as crystallization or solvent extraction. If necessary the product(s) are purified by standard methods.

Compounds of Formula 0 can be converted to compounds of Formula P by displacement of the halogen radical X₁ by a suitable nucleophile. Formation of products of Formula P can be carried out by treatment of compounds of Formula O with an alkoxide, thioalkoxide, amine, alkyl or aryl anion, etc., or an alcohol, mercaptan, amine, etc. in the presence of a base in any suitable solvent. The preferred solvents are dimethylsulfoxide, acetone, dimethylformamide, dioxane, etc. The base may be an organic base (such as a trialkylamine or another organic amine) or an inorganic base (an alkali carbonate such as potassium carbonate or sodium carbonate). Reaction temperature is in the range of 0ºC to 150ºC, preferably 10ºC to 100ºC. The reaction period may be chosen from the range of a few minutes to several weeks depending on the amounts of reagents, reaction temperature, etc. The product is isolated after completion of the reaction by filtration and/or concentration of the reaction mixture. If necessary, the product is purified by standard methods such as

extraction, crystallization, column chromatography, etc.

Formation of products of Formula R can be carried out by acid hydrolysis of compounds of Formula Q. To effect acid hydrolysis, compounds of Formula Q are subjected to an excess of a mineral acid such as hydrochloric acid or sulfuric acid, with a large excess of sulfuric acid being preferred. Reaction temperature is in the range of 0ºC to the boiling point of the inert solvent, preferably 10ºC to 100ºC. The reaction period may be chosen from the range of a few minutes to several weeks depending on the amounts of reagents, reaction temperature, etc. After completion of the reaction the product or products are isolated by diluting the reaction mixture with water and the product (s) are isolated by a method such as crystallization or solvent extraction. If necessary, the product(s) are purified by standard methods.

Compounds of Formula S are obtained by

oxidation of Formula R compounds. Any suitable inert solvent may be employed in this reaction including hydrocarbons, aromatic hydrocarbons, pyridine and its derivatives, water, etc. Oxidizing agents employed include but are not limited to peroxides such as

potassium permanganate or potassium dichromate.

Reaction temperature is in the range of 0ºC to the boiling point of the inert solvent, preferably 10ºC to 100ºC. The reaction period may be chosen from the range of a few minutes to several weeks depending on the amounts of reagents, reaction temperature, etc. After completion of the reaction the product or products are isolated by diluting the reaction mixture with water and the product(s) are isolated by a method such as crys tallization or solvent extraction. If necessary, the product(s) are purified by standard methods.

The last step of this process is meant to include the transformation of compounds of Formula S to compounds of Formula T by any of the variety of standard techniques for preparation of derivatives of carboxylic acids. This process step is an esterification or an amide-forming reaction. This may be accomplished directly from a compound S or via an alkali metal salt of a compound S. The esterification can be carried out by using an excess of the alcohol corresponding to the objective ester in the presence of a mineral acid (e.g., sulfuric acid). The amide derivatives can be prepared by treating a compound S with the desired amine either neat or in a suitable solvent. The esterification or amide-forming reactions can also be carried out in the presence of an inert solvent and a dehydrating agent.

Alternatively, compounds of Formula S can be nverted to an acid halide or anhydride and treated with an alcohol or amine. Preparation of the acid halide is carried out in the presence of a halogenating agent such as, but not limited to, thionyl chloride, phosphorus pentachloride, oxalyl chloride, etc., with or without an inert solvent. Any inert solvent which does not interfere with the reaction may be employed. A catalytic amount of an amine base such as triethylamine, pyridine or dimethylformamide or the like may be added for the purpose of promoting this reaction. The reaction temperature is in the range of -20ºC to the boiling point of the solvent used. The reaction period ranges from several minutes to 48 hours depending upon the amounts of reactants used and the reaction temperature. After completion of the reaction, the excess halogenating reagent and solvent(s) are removed from the reaction product by evaporation or distillation. The resultant acid halide may be subjected to an amine or alcohol directly and purified by the usual means. The acid halide is treated with an alcohol or amine to give a compound or Formula T. Any inert solvent may be employed and a catalytic amount of an amine base such as triethylamine, pyridine or

dimethylformamide or the like may be added for the purpose of promoting this reaction. The reaction temperature is in the range of -20ºC to the boiling point of the solvent used. The reaction period ranges from several minutes to 48 hours depending upon the amounts of reactants used and the reaction temperature. The product is isolated after completion of the reaction by filtration and/or concentration of the reaction mixture. If necessary, the product is purified by standard methods such as extraction, crystallization, column chromatography, etc.

PROCESS XI

This section describes a process for the preparation of compounds according to Formula I in which one of the R₄ residues is a thiol group (Formula U) starting with compounds according to Formula I.

In this process, the desired compounds are obtained by preparation of a halosulfonyl intermediate folloved by reduction to give compounds of Formula U. Any solvent may be employed that does not hinder the progress of the reaction such as halogenated hydrocarbons, ethers, alkylnitriles, mineral acids, etc. An excess of chlorosulfonic acid is preferred as both the reagent and solvent for the formation of chlorosulfonyl intermediates. The reaction temperature is in the range of 25ºC to the boiling point of the solvent employed. The reaction period may be chosen from the range of a few minutes to several weeks depending on the amounts of reagents, reaction temperature, etc. After completion of the reaction the product or products are isolated by diluting the reaction mixture with water and the product(s) are isolated by a method such as crystallization or solvent extraction. If necessary, the product(s) are purified by standard methods.

Reduction of the halosulfonyl intermediate can be carried out in inert solvents including either

organic or inorganic acids, such as acetic acid or hydrochloric acid, and may be used as concentrated acid solutions or dilute aqueous solutions. Reducing agents suitable in an acidic medium include, but are not limited to, metals such as iron, zinc or tin. The reaction solvent can include Reaction temperature is in the range of 0ºC to 150ºC, preferably 10ºC to 100ºC.

The reaction period may be chosen from the range of a few minutes to several weeks depending on the amounts of reagents, reaction temperature, etc.

After completion of the reaction the product is isolated by diluting the reaction mixture with water and the product is isolated by a method such as crystallization or solvent extraction. If necessary, the product is purified by standard methods.

PROCESS XII

In this process step, compounds of Formula V (Formula I compounds in which R₂ is CH₂R₂₃ where R₂₃ is one of the previously defined R₄ members) are prepared from compounds of Formula I where R₂ is methyl.

Any suitable solvent may be employed provided that it is anhydrous, does not react with water, and does not interfere with the course of the reaction.

Preferably, anhydrous ethers such as tetrahydrofuran, diethyl ether or polyethers are employed. The reaction temperature is usually -100ºC to the boiling point of the solvent employed with -78ºC to 25ºC being preferred. Initially, the compound of Formula I is treated with a strong base such as an alkyl metal, metal hydride, metal amide, etc., folloved by treatment with an alkylating agent such as an alkyl halide, an alkyl sulfonate, etc. The reaction period may be chosen from the range of a few minutes to several weeks depending on the amounts of reagents, reaction temperature, etc.

After completion of the reaction the product is isolated by diluting the reaction mixture with water and the product is isolated by a method such as crystallization or solvent extraction. If necessary, the product is purified by standard methods.

PROCESS XIII

This process step describes the conversion of compounds of Formula W to either compounds of Formulae X or Y. The radical R₂₄ is as previously defined for one of the R₄ members and n is an integer of 0 or 1.

In this process step, the nitro radical of compounds according to Formula W is reduced to give an amine derivative which can either be isolated or allowed to cyclize directly to give products of Formulae X or Y depending on the nature of the R₂₄ radical. In some cases, it may be necessary to carry out the above reactions at elevated temperatures in order to facilitate cyclization of the amine intermediate. Reducing agents suitable in an acidic medium include, but are not

limited to, metals such as iron, zinc or tin. The reaction solvent can include either organic or inorganic acids, such as acetic acid or hydrochloric acid, and may be used as concentrated acid solutions or dilute aqueous solutions. Reaction temperature is in the range of 0ºC to 150ºC, preferably 10ºC to 100ºC. The reaction period may be chosen from the range of a few minutes to several weeks depending on the amounts of reagents, reaction temperature, etc.

After completion of the reaction the product is isolated by diluting the reaction mixture with water and the product is isolated by a method such as

crystallization or solvent extraction. If necessary, the product is purified by standard methods.

Alternatively, compounds of Formula W may be reduced by catalytic hydrogenation. For catalytic hydrogenation, which may be carried out at normal or elevated pressures, suitable catalysts include Raney nickel, palladium-carbon, palladium black, palladium on any suitable support, palladium oxide, platinum, platinum black, etc. Solvents include any inert solvent which does not markedly hinder the reaction including alcohols, ethers, etc. The product is isolated after completion of the reaction by filtration and concentration of the reaction mixture. If necessary, the product is purified by standard methods such as extraction, crystallization, column chromatography, etc. The following Examples 1-27 describe specific working embodiments for the preparation of representative compounds according to this invention. In the examples which follow, where chromatographic purifications were done the adsorbent material was silica.

Examples 1-3 describe specific working

embodiments of Process I, used to prepare intermediate compounds for preparing the final products of this invention.

Example 1

(A.) All equipment was flame dried under N₂. To a slurry of 5.4 g (0.18 mole) 80% oil dispersion NaH in 150 mL dry DMSO was added 14.04 g (0.09 mole) 2,5-difluoroacetophenone (commercially available) over 10 min. A gas evolution was noted. The reaction was cooled to 15º and 5.4 mL (0.09 mole) CS₂ vere added over 15 min. keeping the temperature at 15ºC and the gas evolution under control. 11.1 mL (0.018 mole) methyl iodide was added immediately after the completion of the CS₂ addition at 20ºC. The reaction was stirred for 2 hr. at room temperature. The reaction mixture was poured into 500 mL ice and stirred for 1 hr. The solid was filtered, washed with water and air dried. The residue was purified chromatographically using 20% ethyl acetate in hexane as the eluent to give 19.8 g (85%) of 1-(2,5-difluorophenyl)-3,3-bis(methylthio)-2-propen-1-one as a yellow solid, mp 105.5ºC;

Alternatively, for the procedure described in step (A.) a mixture of anhydrous solvents can also be used, e.g., a mixture of DMSO and THF.

Anal. Calc. for C₁₁H₁₀F₂O₁S₂: 0,50.75; H,3.87; S,24.63.

Found: 0,50.85; H,3.86; S,24.75. (B.) To a slurry of 4.0 g (0.0154 mole) of the product of step (A.) in 50 mL acetonitrile was added 1.65 mL (0.031 mole) methylhydrazine over 15 min. at 24ºC. The solution was refluxed for 6 hr. The solution was stripped in vacuo. The residue was purified chromato graphically using 10% ethyl acetate in hexane as the eluent to give 3.05 g (82%) of 3-(2,5-difluorophenyl)- 1-methyl-5-(methylthio)-1H-pyrazole as a light yellow oil;

Anal. Calc. for C₁₁H₁₀F₂N₂S₁: C, 54.99; H,4.20; N, 11.66;

S,13.34.

Found: C,55.03; H,4.26; N, 11.55;

S.13.38.

Example 2

This example describes the preparation of an isomeric mixture of 3-(2,5-difluorophenyl)-1-methyl-5-methylthio-1H-pyrazole and 5-(2,5-difluorophenyl)-1-methyl-3-methylthio-1H-pyrazole.

A. To a solution of 5.2 g 1-(2,5-difluorophenyl)-3,3-bis(methylthio)-2-propen-1-one in 50 mL acetonitrile at

24ºC was added 1.3 mL of anhydrous hydrazine over a period of 3 minutes. The reaction was heated to 95ºC for l hour. The reaction was concentrated in vacuo.

The residue was taken up in diethyl ether and washed with water, dried over anhydrous MgSO₄, and concentrated in vacuo . The residue was recrystallized from hexane to give 4.14 g (94%) of 3-(2,5-difluorophenyl)-5-(methylthio)-1H-pyrazole as a white solid, mp 88ºC.

Anal. Calc. for C₁₀H₈F₂N₂S₁: C,53.09; H,3.56; N,12.38;

S,14.17.

Found: C,53.12; H,3.55; N,12.40;

S,14.15.

B. A slurry of 3.44 g of the product of Step A, 2.2 g K₂CO₃, and 1.0 mL methyl iodide in 75 mL acetone was stirred overnight at 25ºC. The solution was diluted with 300 mL cold water and extracted three times with ethyl acetate. The ethyl acetate extracts were washed with brine, dried over anhydrous MgSO₄, and concentrated in vacuo. The residue was purified chromatographically using 10% ethyl acetate in hexane as the eluent to give 2.97 g (85%) of 3-(2,5-difluorophenyl)-1-methyl-5-methylthio-1H-pyrazole (analysis given in Example 1) and 0.35 g (10%) of 5-(2,5-difulorophenyl)-1-methyl-3- (methylthio)-1H-pyrazole as a light yellow oil, nf

1.5731.

Anal. Calc. for C₁₁H₁₀F₂N₂S₁: 0,54.99; H,4.20; N,11.66.

Found: C,54.83; H,4.19; N,11.85.

Example 3

This example describes the preparation of 3- (2,4-difluorophenyl)-1-methyl-5-(methylthio)-1H-pyrazole.

All glassware was flame dryed. To a mechanically stirred solution of potassium t-butoxide (43g 0.38mol) in anhydrous tetrahydrofuran (600ml) was added 2,4-difluoroacetophenone (30g, 0.192mol). The solution exothermed to 40ºC and was stirred at that temperature for 30 minutes. The solution was then cooled to 0ºC and a solution of carbon disulfide (11.6 ml, 0.192 mol) was added at such a rate that the temperature of the reaction never exceeded 1ºC. After the addition was

complete, the reaction was stirred for 15 minutes at 0ºC, followed by the addition of methyl iodide (23.6g, 0.38 mol) never letting the solution temperature rise above 1ºC. The solution was stirred using no cooling until it reached 10ºC, at which time the reaction solution was poured onto 1L of ice water. Two crops of a filterable yellow solid were collected to give a total yield of 48.1g (96% yield) of the dithioketal. The dithioketal (47g, 0.180 mol) was dissolved in acetonitrile (500 ml) and methyl hydrazine (21g, 0.45 mol) was added all in one portion. The solution was brought to reflux for 24 hours and then most of the acetonitrile was stripped off under vacuum. The remaining liquid was poured onto ice water and extracted into diethyl ether. The organics were washed with brine three times and dried over anhydrous magnesium sulfate, and stripped of all volatiles to give 37.77g (87% yield) of 3-(2,4-difluorophenyl)-1-methyl-5-(methylthio)-1H-pyrazole as an amber oil. ¹HNMR (CDCl₃) ppm: 7.82 (q, J=6.6, 1H), 6.78 (m, 2H), 6.55 (d, J=3.6, 1H) , 3.83 (s, 3H), 2.34 (s, 3H). Anal. Calc. for C₁₁H ₁₀F₂N₂S₁ : C, 54.99 ; H, 4.20; N, 11.66

Found: C,55.06; H,4.23; N, 11.60.

Examples 4, 5 and 6 describe specific vorking

embodiments of Process II.

Example 4

This example describes the preparation of 3- (2,5-difluorophenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole.

A solution of 2.66 g (0.011 mole) of the product of step (B), Example 1, in 50 mL methylene chloride was cooled to -5ºC. A solution of 7.6 g (0.022 mole) 50-60% m-chloro-perbenzoic acid in 100 mL methylene chloride was added to the reaction mixture and allowed to stir overnight at room temperature. The solution was washed with a saturated sodium bicarbonate solution containing 5% sodium thiosulfate, followed by a water wash, dried over anhydrous MgSO₄, and concentrated in vacuo. The residue was recrystallized from methylcyclohexane to give 2.8 g (93%) of 3-(2,5-difluorophenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole as a white solid, mp 126-127ºC; Anal. Calc. for C₁₁H ₁₀F₂O₂S₁: 0,48.53; H,3.70; N, 10.29;

S,11.78.

Found: C,48.61; H,3.70; N, 10.26;

S, 11.71.

Example 5

This example describes the preparation of 5- (4-chloro-2-fluoro-5-methoxyphenyl)-3-(methylsulfonyl)- 1H-pyrazole.

To a solution of 1.12 g of 5-(4-chloro-2- fluoro-5-methoxyphenyl)-3-(methylthio)-1H-pyrazole in a mixture of 30 mL of glacial acetic acid and 15 mL of ethanol vas added 3.2 g of Oxone®. The heterogeneous mixture was heated to 85ºC and after 2 hours was poured into ice water. The resultant mixture was extracted three times vith methylene chloride and the organic extracts concentrated to afford an oily residue.

Solution of the oily residue in 10% aqueous NaOH folloved by neutralization with concentrated HCl afforded a solid precipitate which was collected and washed with water to afford 0.60 g (48%) of 5-(4-chloro-2-fluoro-5-methoxyphenyl)-3-(methylsulfonyl)-1H-pyrazole. An analytical sample was obtained by

recrystallization from methanol/water to give a yellow, crystalline solid; mp 213-216 (dec).

Anal. Calc. for C₁₁H ₁₀N₂O₃F₁: 0,43.36; H,3.31; N,9.19;

S, 10.52.

Found: 0,43.51; H,3.33; N,9.10;

S, 10.44.

Example 6

This example describes the preparation of 4-chloro-3- (2-fluoro-4-methoxyphenyl) -1-methyl-5- (methylsulfonyl) -1H-pyrazole.

To a 0 º 0 solution of 4-chloro-3- (2-fluoro-4-methoxyphenyl) -1-methyl-5- (methylthio) -1H-pyrazole

( 3. 5g , 0.0122 mol) in methylene chloride ( 150 mL) was added m-chlorobenzoic acid in small portions . The reaction was stirred for 20 hours at room temperature, then the organics were extracted tvice with a 50% solution of saturated sodium bicarbonate in saturated sodium thiosulfate solution. The organics were dried over anhydrous magnesium sulfate and the volatiles removed under vacuum to give a yellow solid with mp = 75 º C.

Anal. Calc. for C₁₂H ₁₂F₁N₂O₃ S₁Cl₁ : C, 45.22 ; H, 3.79 ;

N,8.79.

Found: 0,45.49; H,3.77;

N,8.69.

Examples 7 and 8 describe specific working embodiments of Process III.

Example 7

This example describes the preparation of 4- chloro-3-(2,5-difluorophenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole.

At 25ºC, 2.25 g (8.2 mmole) of the product of Example 4 was dissolved in 40 mL glacial acetic acid and 1.1 g (16.4 mmole) chlorine gas was bubbled in over a period of 50 minutes. The reaction was a1loved to stir for 45 minutes. The reaction solution was poured into 300 mL ice water, and extracted with diethyl ether. The ether was washed with a saturated sodium bicarbonate solution, dried over anhydrous MgSO₄, and concentrated in vacuo. The residue was purified chromatographically using 30% ethyl acetate in hexane as the eluent to give 1.35 g (84%) of 4-chloro-3-(2,5-difluorophenyl) 1-methyl-5-(methylsulfonyl)1H-pyrazole as a white solid, mp 77ºC; Anal. Calc. for C₁₁H₉Cl₁F₂N₂O₂S₂: C,43.08; H,2.96; N-9.13;

S,10.45; 01,11.56.

Found: C,43.16;H,2.97;N,9.12;

S,10.39; Cl, 11.49.

Example 8

This example describes the preparation of 4-chloro-3-(2-fluoro-4-methoxyphenyl)-1-methyl-5-(methylthio)-1H-pyrazole.

To a 0ºC solution of 3-(2-fluoro-4-methoxyphenyl)-1-methyl-5-(methylthio)-1H-pyrazole (4g, 0.015 mol) in diethyl ether (30 ml) and 1 drop of glacial acetic acid was added 1,3-dichloro-5,5-dimethylhydantoin (1.77 g, 0.009 mol). The reaction was stirred for one hour at room temperature and then poured onto ice. The organics vere extracted into diethyl ether, washed with brine, dried over anhydrous magnesium sulfate and stripped in vacuo to give a yellow oil, n_D ²⁵ =

1.5943 at 25ºC.

Anal. Calc. for C₁₂H₁₂F₁N₂O₁S₁Cl₁: 0,50.26; H,4.22; N-9.77.

Found: 0,49.84; H.4.13; N,9.61. Examples 9 and 10 describe specific vorking embodiments of Process IV.

Example 9

This example describes the preparation of 4- chloro-3-(2,5-difluoro-4-nitrophenyl)-1-methyl-5- (methylsulfonyl)-1H-pyrazole. At 24ºC, 1.5 g (4.9 mmole) 4-chloro-3-(2,5-difluorophenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole, was slowly added to 25 mL of fuming nitric acid. The reaction was stirred at 30ºC for 30 minutes. The reaction was poured into 300 mL of ice. The slurry was filtered and the cake washed veil with water and air dried. The solid was recrystallized from methylcyclohexane to give 1.13 g (66%) of 4-chloro-3-(2,5-difluoro-4-nitrophenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole as a beige solid, mp 147ºC;

Anal. Calc. for C₁₁H₈Cl₁F₂N₃O₄S₁: 0,37.56; H,2.29; N,11.95;

S.9.12.

Found: C,37.60; H,2.29;N,11.98;

S.9.10.

Example 10

This example describes the preparation of 4-chloro-3-(4-chloro-2-fluoro-5-nitrophenyl)-1-methyl-5- (methylsulfonyl)-1H-pyrazole.

To a solution of 3g (0.0093 mol) of 4-chloro-3-(4-chloro-2-fluorophenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole in 3 mL of concentrated sulfuric acid was added a mixture of 1 mL of concentrated nitric acid in 3 mL concentrated sulfuric acid, dropvise. This mixture was then stirred at 25ºC for 2 hours. The reaction mixture was then poured into ice-water and extracted with ether. The organic extracts vere then washed three times with 100 mL of aqueous NaCl, dried (MgSO₄) , filtered and concentrated to afford 2.3g (67%) of 4- chloro-3-(4-chloro-2-fluoro-5-nitrophenyl)-1-methyl-5- (methylsulfonyl)-1H-pyrazole as a yellow solid.

Chromatography (10% EtOAc/CH₂Cl₂) afforded an analytical sample, mp 111-115ºC.

Anal. Calc. for C₁₁H₈N₃O₄Cl₂F₁S₁ + 1/4 EtOλc:

C, 36.45; H,2.60; N, 10.85.

Found: 0,36.39; H,2.26; N, 10.91.

Examples 11 and 12 describe specific vorking embodiments of Process V. Example 11

This example describes the preparation of 4-chloro-3-(2-fluoro-5-methoxy-4-nitrophenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole.

A mixture of 4.8 g (0.0137 mole) of the product of Example 9, 1.9 g (0.014 mole) K₂CO₃, and 5 mL methanol was slurried in 50 mL DMSO at 25ºC. The reaction was stirred at 45ºC for 8 hours. The reaction was cooled, diluted with 100 mL cold water, and

extracted four times with ethyl acetate. The ethyl acetate extracts vere washed with brine, dried over anhydrous MgSO₄, and stripped in vacuo. The residue was recrystallized from ethyl acetate/hexane to give 4.21 g (84%) of 4-chloro-3-(2-fluoro-5-methoxy-4-nitrophenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole as a yellow solid, mp 178.5-180ºC;

Anal. Calc. for C₁₂H₁₁Cl₁F₁N₃O₅S₁: C,39.62; H,3.05;

N, 11.55; S,8.81.

Found: C,39.58; H,2.98;

N, 11.54; S,8.59.

Example 12

This example describes the preparation of 5- [4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl]-4-fluoro-N-(1-methylethyl)-2-nitrobenzenamine.

To a solution of 4-chloro-3-(2,5-difluoro-4-nitrophenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole (7.6g, 0.0218 mol) in n-methyl pyrrolidinone (50 ml) was added isopropyl amine (1.94g, 0.0328 mol), potassium carbonate (4.5g, 0.0328 mol) and a catalytic amount of copper (II) fluoride. The reaction was heated to 60ºC for two hours and determined complete by TLC. The reaction was diluted into ethyl acetate and the organics were washed three times with brine, dried over anhydrous magnesium sulfate and the volatiles removed under vacuum to give 8.4g (98%) of 5-[4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl]-4-fluoro-N-(1-methylethyl)- 2-nitrobenzenamine as an orange solid after recrystalization from ethanol/methyl cyclohexane, mp 152ºC. Anal. Calc. for C₁₄H₁₆Cl₁F₁N₄O₄S₁: C,43.03; H,4.13; N, 14.34.

Found: C,43.09; H,4.09; N, 14.36.

Example 13

This example describes the preparation of 4-chloro-3-(4-chloro-2-fluoro-5-methoxyphenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole is a specific embodiment of Process VI.

(A.) A slurry of 3.3 g (9.1 mmole) of 4-chloro-3-(2-fluoro-5-methoxy-4-nitrophenyl)-1-methyl-5-(methyl-sulfonyl)-1H-pyrazole in 100 mL of acetic acid was heated to 80ºC under nitrogen and treated portionvise with 1.5 g (27 mmole) of iron povder. After 20 minutes at 85ºC, the mixture was alloved to cool and filtered through Celitee. The resultant solution was diluted with 250 mL of water and extracted three times with ethyl acetate. The organic extracts were washed with water, saturated aq. NaHCO₃, vater, dried with MgSO₄ and concentrated to afford 3.1 g of a tan solid.

(B.) A solution of 3.0 g (9.0 mmole) of the product of step (A.) in 70 mL dry acetonitrile at 25ºC was treated with 0.9 g (9.0 mmole) CuCl and 1.8 g (13.1 mmole) CuCl₂. A solution of 2.4 mL (18 mmole) 90% t-butyl nitrite was added to the reaction mixture over 5 minutes. After 1 hour at 28ºC the reaction mixture was concentrated in vacuo. The reaction residue was taken up in ethyl acetate and washed three times with a 10% HCl solution, two times with brine, dried over anhydrous MgSO₄, and concentrated in vacuo. The residue was purified

chromatographically using 50% ethyl acetate in hexane as the eluent to give 2.64 g (83%) of 4-chloro-3-(4-chloro- 2-fluoro-5-methoxyphenyl)-1-methyl-5-(methylsulfonyl)- 1H-pyrazole as a white solid, mp 127.5ºC

Anal. Calc. for C₁₂H₁₁Cl₂₂F₁N₂O₃S₁: C,40.81; H,3.14;

N,7.93; S,9.08; Cl, 10.08. Found: C,40.94; H,3.14;

N, 7.88 ; S, 8.97 ; Cl, 19.95. Examples 14-16 describe specific working embodiments of Process VII . Examole 14

This example describes the preparation of 2- chloro-5-[4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl]-4-fluoro-N-2-propenylbenzenamine.

A solution of 1 g (0.0023 mol) of N-[2-chloro- 5-[4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl]-4-fluorophenyl]-2,2,2-trifluoroacetamide, 0.97 g (0.007 mol) of potassium carbonate, 25 mL of anhydrous DMF and 0.85g (0.007 mol) of allyl bromide was allowed to stir at 70ºC for 24 hours. This solution was diluted with EtOAc, washed with three times 100 mL of 5% HCl, dried (MgSO₄), filtered and concentrated to afford 0.9g of a red oil. This oil was dissolved in 20 mL of methanol and 3 mL of 10% NaOH was added. This mixture was stirred at 25ºC for 8 hours. The reaction mixture was diluted with EtOAc, washed with three times 100 mL of aqueous NaCl, dried (MgSO₄) , filtered and concentrated to afford 0.8g of a red oil. Chromatography (CH₂Cl₂) afforded 0.6g (69%) of 2-chloro-5-[4-chloro-1-methyl-5- (methylsulfonyl)-1H-pyrazol-3-yl]-4-fluoro-N-2-propenyl- benzenamine as a yellow oil, n_D ²⁵ = 1.5956.

Anal. Calc. for C₁₄H₁₄N₃O₂Cl₂F₁S₁: C,44.46; H,3.73; 11,11.11.

Found: C,44.66; H,3.68; N, 10.85.

Example 15

This example describes the preparation of N- [2-chloro-5-[4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl]-4-fluorophenyl]-methanesulfonamide.

To a solution of 0.5g (0.001 mol) of N-[2-chloro-5-[4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl]-4-fluorophenyl]-N-(methylsulfonyl)-methanesulfonamide in 20 mL of methanol was added 2 mL of 10% NaOH. This mixture was stirred at 25ºC for 4 hours. The reaction mixture was diluted vith EtOAc, washed with three times 100 mL of 5% HC1, dried (MgSO₄) , filtered and concentrated to afford 0.2g (48%) of N-[2- chloro-5-[4-chloro-1-methyl-5-(methylsulfonyl)-1H- pyrazol-3-yl]-4-fluorophenyl]methanesulf onamide as a yellow-tan solid. Chromatography (EtOAc) afforded an analytical sample, mp 165-166 º0.

Anal . Calc. for C₁₂H₁₂N₃O₄Cl₂F₁S₂ + 1/4 EtOAc:

C, 35.18 ; H - 3.24 ; N, 9.65.

Found: C, 35.09 ; H, 2.97 ; N, 9.90.

Example 16

This example describes the preparation of 4-chloro-3-(4-chloro-2-fluoro-5-hydroxyphenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole.

A solution of 1.15 g (3.25 mmole) 4-chloro-3- (4-chloro-2-fluoro-5-methoxyphenyl)-1-methyl-5-(methyl¬sulfonyl)-1H-pyrazole in 30 mL methylene chloride was chilled to 0ºC and treated with 4 mL of a 1M methylene chloride solution of BBr₃ (4.0 mmole) was added slowly over 5 minutes. The solution was alloved to stir overnight at room temperature. The solution was washed two times with water, dried over anhydrous MgSO₄, and concentrated in vacuo. The residue was recrystallized from hexane to give 1.1 g (100%) of 4-chloro-3-(4-chloro-2-fluoro-5-hydroxyphenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole as a beige solid, mp 190.5ºC; Anal. Calc. for C₁₁H₉Cl₂F₁N₂O₃S₁: C, 38.95; H,2.67, N,8.26.

Found: 0,38.93; H,2.67; N,8.43. Examples 17, 18, 19 and 20 describe specific vorking embodiments of Process VIII.

Example 17

This example describes the preparation of 2- chloro-5-[4-chloro-1-methyl-5-(methylsulfonyl)-1H- pyrazol-3-yl]-4-fluoro-N-(1-methylethyl)-benzeneamine.

λ solution of 0.5g (0.0015 mol) of 2-chloro- 5-[4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3- yl]-4-fluorobenzenamine and 2 mL of 2-iodopropane in 5 mL of anhydrous DMF was stirred at 75ºC for 6 hours, then at 25ºC for 2-1/2 days. The reaction mixture was diluted with EtOAc, washed with two times 50 mL of 5% HCl, dried (MgSO₄), filtered and concentrated to afford 0.5g red oil. Chromatography (methylene chloride) afforded 0.25g (44%) of 2-chloro-5-[4-chloro-1-methyl 5- (methylsulfonyl) -1H-pyrazol-3-yl]-4-fluoro-N- (1-methylethyl) -benzeneamine as a red solid, mp 118 º0-121 º C.

Anal . Calc. for C₁₄H₁₅N₃O₂Cl₂F₁S₁ + 1/2 H₂O:

C, 43.20 ; H, 4.40 ; N, 10.79.

Found: C, 42.88 ; H, 4.02 ; N, 10.70.

Example 19

This example describes the preparation of N-[2-chloro-5-[4-chloro-1-methyl-5- (methylsulfonyl) -1H-pyrazol-3-yl]-4-fluorophenyl]-alanine, ethyl ester.

A solution of alanine, N-[2-chloro-5-[4-chloro-2-methyl-5-(methylsulfonyl) -1H-pyrazol-3-yl]-4-fluorophenyl] - in ethanol with a catalytic amount of acetyl chloride vas al lowed to stir at 25 ºC for 18 hours. This solution vas diluted with EtOAc, washed with water , two times with 100 mL of aqueous potassium carbonate, dried (MgSO₄) , filtered and concentrated to afford 0.5g of a yellov oil. Chromatography (CH₂Cl₂) afforded 0.17g (20%) of N-[2-chloro-5-[4-chloro-1-methyl-5- (methylsulfonyl) -1H-pyrazol-3-yl] -4-fluoro¬phenyl] -alanine, ethyl ester as a yellov oil. ¹HNMR (400 MHz , CDCl₃) d 1.2 (5 , 3H) , 1.48 (d, 3H) , 3.23 (s , 3H) , 3.8 (q, 1H) , 4.15 (q, 2H) , 4.18 (s, 3H) , 4.7 (bs, 1H) , 6.6 (d, 1H) , 7.1 (d, 1H) ppm: ; ¹⁹FNMR(360MHz, CDCl₃ d - 128 (s, 1F) ppm.

Anal. Calc. for C₁₆H₁₈NO₄Cl₂F₁S₁: 0,43.85; H,4.14; N,9.59.

Found: C,43.90; H,4.11; N,9.52.

Example 19

This example describes the preparation of N- [2-chloro-5-[4-chloro-1-methyl-5-(methylsulfonyl)-1H- pyrazol-3-yl]-4-fluorophenyl]-N-(methylsulfonyl)methanesulfonamide.

To a solution of 0.5g (0.0015 mol) of 2- chloro-5-[4-chloro-1-methyl-5-(methylsulfonyl)-1H- pyrazol-3-yl]-4-fluorobenzeneamine in 20 mL of methylene chloride was added 0.33g (0.0033 mol) of triethylamine folloved by 0.37g (0.0033 mol) of methanesulfonyl chloride. This mixture was stirred at 25ºC for 18 hours. The reaction mixture was diluted with EtOAc, washed with three times 100 mL of 5% HCl, dried (MgSO₄) , filtered and concentrated to afford 0.7g (94%) of N-[2- chloro-5-[4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl]-4-fluorophenyl]-N-(methylsulfonyl)-methanesulfonamide as an off-white solid. Chromatography (EtOAc) afforded an analytical sample, mp 234-237ºC.

Anal. Calc. for C₁₃H₁₄N₃O₆Cl₂F₁S₃ + 1/4 EtOAc:

C,32.17; H,3.14; N,8.18.

Found: C,32.05; H,2.86; N,8.48.

Example 20

This example describes the preparation of 4-chloro-3-(4-chloro-2-fluoro-5-(2-propynyloxy)-phenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole

A mixture of 0.87 g (2.5 mmole) of 4-chloro-3-(4-chloro-2-fluoro-5-hydroxyphenyl)-1-methyl-5- (methylsulfonyl)-1H-pyrazole, 0.4 g (3.0 mmole) K₂CO₃, and 0.3 mL (3.0 mmole) propargyl bromide vere slurried in 10 mL DMSO at 25ºC. The reaction was stirred at 45ºC for 16 hours. The reaction was cooled, diluted with 100 mL cold water, and extracted four times with ethyl acetate. The ethyl acetate extracts vere washed with brine, dried over anhydrous MgSO₄, and stripped in vacuo. The residue was purified chromatographically using 50% ethyl acetate in hexane as the eluent to give 0.93 g (96%) of 4-chloro-3-(4-chloro-2-fluoro-5-(2- propynyloxy)phenyl)-1-methyl-5-(methylsulfonyl)-1H- pyrazole as a tan solid, mp 135ºC. Anal. Calc. for

C₁₄H₁₁Cl₂F₁N₂O₃S1: C44.58; H,2.94, N,7.43.

Found: 0,44.75; H,3.08;N,7.36

Examples 21 and 22 describe specific working embodiments of Process IX.

Example 21

This example describes the preparation of 2- (2-chloro-5-(4-chloro-1-methyl-5- (methylsulfonyl) -1H- pyrazol-3-yl) -4-fluorophenoxy) -propanoic acid. To a slurry of 3.77 g (8.6 mmole) 2-(2-chloro-5-(4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl)-4-fluorophenoxy)-propanoic acid, ethyl ester in 20 mL water and 20 mL 1,4-dioxane was added 3.5 mL (8.6 mmole) 10% aqueous NaOH. The reaction became clear after 30 min. and a TLC indicated that the reaction was complete. The solution was cooled and the pH adjusted to 3 with concentrated HCl. The reaction was extracted with ethyl acetate. The extracts vere washed with water, dried over anhydrous MgSO₄, and concentrated in vacuo. The residue was recrystallized from hexane to give 2.9g (83%) of 2-(2-chloro-5-(4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl)-4-fluorophenoxy)-propanoic acid as a white solid, mp 56ºC.

Anal. Calc. for C₁₄H₁₃Cl₂F₁N₂O₅S₁:

C40.80; H,3.19; N,6.81.

Found: 0,40.87; H,3.24; N,6.69.

Example 22

This example describes the preparation of 2- (2-chloro-5-(4-chloro-1-methyl-5-(methylsulfonyl)-1-pyrazol-3-yl)-4-fluorophenoxy)-N-methylpropanamide.

To a solution of 1.17g (5.9 mmole) 2-(2-chloro-5-(4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl)-4-fluorophenoxy)-propanoic acid in 10 mL methylene chloride was added 0.8 mL (9.6 mmole) oxalyl chloride over 3 minutes, causing the evolution of gas. When this evolution ceased, one drop of DMF was added and the solution stirred until the gas evolution ceased. The solution was stripped to dryness in vacuo. The residue was dissolved in 5 mL THF and at 0ºC added to 10 mL of a 40% aqueous solution of methyl amine over 5 minutes. The reaction mixture was a1loved to stir for 30 minutes at room temperature. The solution was poured into 150 mL cold water and extracted with ethyl acetate. The ethyl acetate extracts vere washed times with brine, dried over anhydrous MgSO₄, and stripped in vacuo. The solid was recrystallized from methylcyclohexane/ethyl acetate to give 0.96g (80%) of 2-(2-chloro-5-(4-chloro- 1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl)-4-fluoro¬phenoxy)-N-methylpropanamide as a white solid, mp 178ºC; ¹HNMR (CDCl₃) ppm: 1.55 (d, 3H) , 2.81 (d, 3H) , 3.23 (s, 3H), 4.17 (s, 3H), 4.64 (q, 3H) , 6.65 (br, 1H) , 6.97 (d, 1H), 7.22 (d, 1H).

Anal. Calc. for C₁₅H₁₆Cl₂F₁N₃O₄S₁: C-42.46; H.3.80; N,9.90.

Found: C,42.60; H,3.68; N,9.86. Examples 23 and 24 describe specific vorking embodiments of Process X.

Example 23

This example describes the preparation of ( ( (2-chloro-5-(4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl)-4-fluorophenyl)methyl)thio) acetic acid, ethyl ester.

At 25ºC, 1.25g (3.0 mmole) 3-(5-(bromomethyl)- 4-chloro-2-fluorophenyl)-4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazole, 0.5g (3.3 mmole) K₂CO₃, and 0.4 mL (3.3 mmole) ethyl bromoacetate vere slurried in 15 mL acetone. The reaction was stirred at 20ºC for 8 hours. The reaction was poured into 150 mL water, filtered and air dired. The solid was recrystallized from methyl-cyclohexane to give 1.2g (93%) of (((2-chloro-5-(4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl)-4-fluorophenyl)methyl)thio)acetic acid, ethyl ester as a white solid, ap 110ºC.

Anal. Calc. for C₁₆H₁₇Cl₂F₁N₂O₄S₂: 0,42.20; H,3.76; 11,6.15.

Found: 0,42.25; H,3.72; N,6.18.

Example 24

This example describes the preparation of 2-chloro-5-(4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl)-4-fluoro-N-methylbenzamide.

To a solution of 1.34g (3.7 mmole) 2-chloro- 5-(4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3- yl)-4-fluorobenzoic acid in 25 mL methylene chloride was added 1.0 mL (11.1 mmole) oxalyl chloride over 3 minutes, causing the evolution of gas. When this evolution ceased, one drop of DMF was added and the solution stirred until the gas evolution ceased. The solution was stripped to dryness in vacuo. The residue was dissolved in 5 mL THF and at 0ºC added to 10 mL of a 40% aqueous solution of methyl amine over 5 minutes.

The reaction mixture was allowed to stir for 30 minutes at room temperature. The solution was poured into 150 mL cold water, filtered, and air dried. The solid was recrystallized from methylcyclohexane/ethyl acetate to give 0.95g (69%) of 2-chloro-5-(4-chloro-1-methyl-5- (methylsulfonyl)-1H-pyrazol-3-yl)-4-fluoro-N-raethylbenzamide as a white solid, mp 187ºC.

Anal. Calc. for C₁₃H₁₂Cl₂F₁N₃O₃S₁ : C,41.07; H,3.18; N,11.05.

Found: C,41.12; H,3.13; N,11.03.

Example 25

This example describes the preparation of 2-chloro-5-(4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl)-4-fluorobenzenethiol and is a specific working embodiment of Process XI.

A slurry of 9.3g (0.022 mole) 2-chloro-5-(4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl)-4-fluorobenzenesulfonyl chloride and 29g (0.44 mole) zinc powder in 125 mL glacial acetic acid was stirred at 90ºC for 4 hours. The slurry was cooled and filtered through Celite^®. The filtrate was poured into 1 liter water and the slurry filtered and air dried. The solid was recrystallized from ethanol/water to give 5.8g (74%) of 2-chloro-5-(4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl)-4-fluorobenzenethiol as a white solid, mp 111ºC.

Anal. Calc. for C₁₁H₉Cl₂F₁N₂O₂S₂: C,37.19; H,2.55; N,7.86;

S, 18.05.

Found: C, 37.29; H,2.44; N,7.86;

S,17.95.

Example 26

This example describes the preparation of 4-chloro-3-(4-chloro-2-fluoro-5-methoxyphenyl)-1-methyl-5-(ethylsulfonyl)-1H-pyrazole and is a specific vorking embodiment of Process XII. All equipment was flame dried unαer nitrogen. To a solution of 4-chloro-3-(4-chloro-2-fluoro-5-methoxyphenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole (1.25g, 3.5 mmol) in 50 ml dry tetrahydrofuran at -78ºC was added a IM solution of n-butyl lithium (3.5 ml, 3.5 mmol) never letting the temperature rise above -60ºC. The reaction was stirred for 30 minutes at -78ºC and then methyl iodide (0.49g, 3.5 mmol) was added to the reaction. The reaction was warmed to room temperature and then poured onto ice and extracted into ethyl acetate. The organics were washed twice with brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The residue was purified chromatographically in 1:1 hexane to ethyl acetate solvent system to give 0.5g (39% Yield) of a yellow solid, mp 65ºC.

Anal. Calc. for C₁₃H₁₃N₂O₃S₁Cl₂: C,42.52; H,3.57; N,7.63.

Found: 0,42.53; H,3.80; N,7.71.

Example 27

This example describes the preparation of 7-[4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl]-6-fluoro-2H-1,4-benzothiazin-4(3H)-one and is a specific vorking embodiment of Process XIII.

A solution of ((5-(4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl)-4-fluoro-2-nitrophenyl) thio)acetic acid, ethyl ester (3.0g, 6.6 mmol) in glacial acetic acid (150 ml) was heated to 80ºC and iron (l.5g, 0.0268 mol) was added all in one portion. The solution was heated betveen 80ºC-100ºC for one hour and then cooled, filtered through Celite® and washed with water until a solid falls out of solution. The solid was filtered off to give 1.7g (68%) of the compound named in the first paragraph of this example as a white solid, mp 245ºC; ¹HNMR (CDCl₃) ppm: 7.28 (d, J = 7.2, 1H), 6.79 (d, J = 10.8, 1H) , 4.1 (S, 3H) , 3.27 (s, 2H), 3.22 (S, 3H).

Anal. Calc. for C₁₃H₁₁Cl₁F₁N₃O₃S₁: C,41.55; H,2.95; N,11.18.

Found: 0,41.72; H,3.09; N, 10.81. Tables 3 and 4 shov examples of compounds prepared by Processes II-XIII and/or any combination of these processes as exemplified in Examples 1-27.

PRE-EMERCEHCE HERBICIDE TESTS

As noted above, the compounds of this invention have been found to be surprisingly effective as herbicides.

The tests for pre-emergence herbicide activity are conducted as follows:

Topsoil is placed in an aluminum pan and compacted to a depth of 0.95 to 1.27 cm from the top of the pan. On the top of the soil is placed a

predetermined number of seeds of each of several

monocotyledonous and dicotyledonous annual plant species and/or vegetative propagules of various perennial plant species, λ known amount of the active ingredient dissolved or suspended in an organic solvent, e.g., acetone, or water as a carrier is then applied directly to the seed bed, which is then covered with a layer of untreated topsoil to level fill the pan. After treatment, the pans are moved to a greenhouse bench where they are watered from below as needed to give adequate moisture for germination and growth.

Approximately 10/14 days (usually 11 days) after seeding and treating, the pans are observed and the results (% inhibition) are recorded.

Table 5 below summarizes the results of the pre-emergence herbicidal activity tests of compounds of this invention against weeds. The herbicidal rating shown in Table 5 is the percent inhibition of each plant species.

The plant species usually regarded as weeds which are utilized in one set of tests, the data for which are shown in Table 5, are identified by letter headings above the columns in accordnace with the following legend: Yens- Yellow nutsedge

Anbg - Annual bluegrass

Sejg - Seedling johnsongrass

Dobr - Downy Brome

Bygr - Barnyardgrass

Mogl - Morningglory

Cobu - Cocklebur

Vele - Velvetleaf

Inmu - Indian Bustard

Wibw - Wild buckwheat

Where noted in the tables below, the symbol "C" represents 100% control and the symbol "N" indicates that the species was planted, but no data obtained for one reason or another.

TABLE 5

PREEMERGENCE TESTS

% PLANT INHIBITION

Y A S D B M C V I W

e n e o y o o e n i cpd. Rate n b j b g g b l a b No. kg/ha s g g r r l u e u w

22 1.12 80 c c c c c 70 c c c

23 1.12 30 20 80 30 20 c 80 90 90 c

24 11.21 70 c 90 70 c 90 70 c c c

25 11.21 0 80 80 70 80 70 30 c c 90

26 11.21 0 0 0 0 0 0 0 80 10 0

27 11.21 0 0 50 20 20 30 40 90 70 10

28 11.21 c c 70 80 c c c c c c

29 11.21 20 c 80 40 c c 0 c c 90

30 1.12 80 40 40 10 80 c c c c c

31 11.21 40 10 70 0 c 80 80 80 80 80

32 11.21 c c c c c c c c c c

33 11.21 90 c 90 c c c 70 c c c

34 11.21 90 c 90 60 c c 70 c c c

35 11.21 90 c c 50 c c 60 c c c

36 11.21 30 30 60 c 90 60 60 c c c

37 11.21 60 80 90 30 c c c c c c

38 11.21 80 80 80 50 c 90 70 90 c c

39 11.21 90 c 90 80 c c c c c c

40 1.12 70 c 70 40 80 c 60 c c 90

41 1.12 70 50 30 10 80 c 20 c c c

42 11.21 80 80 90 80 c c c c c c

43 1.12 70 c c 50 90 c c c c c TABLE 5 (contin eed )

PREEMERGENCE TESTS

% PLANT INHIBITION

Y A S D B M C V I W

e n e o y o o e n i

Cpd. Rate n b j b g g b l m b

No. kg/ha s g g r r l u e u w 44 11.21 90 c c c c c 90 c c c 45 11.21 c c c c c c c c c c 46 1.12 0 0 30 10 0 10 20 70 70 c 47 1.12 0 60 80 10 70 80 10 90 c c 48 1.12 0 30 60 20 c 40 20 80 90 c 49 1.12 0 90 90 10 90 90 30 c c c 50 11.21 20 80 70 60 90 c 20 c 90 c 51 11.21 50 c c 80 c 80 c 90 c c 52 1.12 10 c c 90 90 80 60 c c c S3 1.12 0 10 0 90 4090 50 c c 60 54 1.12 40 10 30 20 0 70 30 c 90 90 55 1.12 10 0 0 20 20 c 90 90 c c 56 1.12 10 90 80 60 70 90 70 c c c 57 1.12 10 0 0 0 0 30 20 70 80 70 58 1.12 7040 70 10 c 90 c c c c 59 11.21 50 c c 80 c 90 90 c c c 60 1.12 30 70 c 90 80 60 40 c 70 c 61 1.12 50 90 60 50 90 c 40 c c c 62 1.12 0 c 80 70 80 90 c 80 C 80 63 1.12 40 50 90 90 c 80 c c c c 64 1.12 30 20 30 80 c 70 C 90 C 90 65 1.12 40 80 70 50 c c 60 c c c TABLE 5 (continued)

PREEMERGENCE TESTS

% PLANT INHIBITION

Y A S D B M C V I W

e n e o y o o e n i Cpd. Rate n b j b g g b l m b

No. kg/ha s g g r r l u a u w

66 1.12 60 c 90 40 c c 70 c c c

67 1.12 0 c 70 80 c c 80 c c c

68 * 1.12 20 90 60 20 90 90 70 c c 90

69 1.12 60 c 90 50 90 c 30 c c c

70 1.12 30 c 90 40 c c 30 c c c

71 1.12 30 c 90 40 c 80 30 c c 90

72 1.12 60 20 60 20 80 c c 90 90 90

73 1.12 50 10 60 30 50 90 80 80 90 80

# 1.12 40 0 80 10 20 90 60 80 90 80

74 1.12 70 20 70 0 80 c c c c c

75 1.12 50 0 70 20 80 c 40 c 90 c

76 1.12 60 20 30 20 70 c 90 90 90 80

77 1.12 20 0 20 20 80 c 70 c 80 80

78 1.12 60 c 90 50 c c c c c c

79 1.12 90 c 70 20 90 c c c c c

80 1.12 60 10 70 20 20 c 60 90 90 90

81 1.12 60 c c 90 c 90 80 c c c

82 1.12 50 50 80 20 90 c 90 c c 90

83 1.12 70 c c c c c 60 c c c

84 1.12 0 80 70 80 80 c 80 c c c

85 11.21 90 90 90 90 90 90 c c c c

86 1.12 0 20 30 20 20 40 20 40 80 90 TABLE 5 (continued)

PREEMERGENCE TESTS

% PLANT INHIBITION

Y A S D B M C V I W

e n e o y o o e n i

Cpd. Rate n b j b g g b l a bNo. kg/ha s g g r r l u e u w

87 1.12 0 70 80 80 60 c 80 c c c

88 1.12 20 40 80 80 60 c 80 c c c

89 1. 12 0 20 40 30 80 80 80 c c c

90 1 . 12 0 0 0 20 30 60 30 c c c

91 1.12 20 10 10 50 70 60 60 c c c

92 1.12 0 80 40 60 50 c 60 c c 90

93 11.21 0 10 0 10 50 20 0 80 80 10

94 11.21 60 c c 70 c 90 30 c c c

95 11.21 70 c c 70 c c 80 c c c

96 11.21 70 c c c c c 20 c c c

97 11.21 20 20 40 20 80 40 20 c c 80

98 11.21 0 0 20 0 0 0 0 0 0 30

99 11.21 0 0 0 0 0 0 0 20 0 0

100 11.21 0 0 0 0 0 0 0 0 0 0

101 11.21 0 0 70 0 80 60 20 50 70 0

102 11.21 40 30 60 30 80 50 0 60 c 90

103 11.21 20 80 80 20 80 90 70 90 80 90

104 11.21 40 c 80 80 90 70 80 c c c

105 11.21 40 80 90 70 90 80 60 c c 70

106 11.21 0 60 70 30 60 40 70 c 90 90

107 11.21 40 90 70 60 c 70 c c c 50

108 11.21 30 90 90 70 80 90 80 c c c TABLE 5 (continued )

PREEMERGENCE TESTS

% PLANT INHIBITION

Y A S D B M C V I W

e n e o y o o e n i

Cpd. Rate n b j b g g b l a b

No. kg/ha s g g r r l u a u w

109 11.21 70 c c 60 90 80 90 c c c

110 11.21 80 c 90 80 90 90 90 c c 80

111 11.21 40 c 70 70 c 20 c c c 70

112 11.21 80 c c 70 90 c 70 c c c

113 1.12 60 80 90 50 c 30 60 90 c 90

114 11.21 0 0 0 20 20 70 20 30 30 20

115 11.21 c 40 90 80 c c c c c c

116 11.21 90 0 80 20 60 90 60 c c c

117 11.21 70 80 90 70 c 70 90 c c c

118 11.21 0 0 0 0 0 0 0 80 20 10

119 11.21 0 0 0 0 0 0 0 30 20 10

120 11.21 0 0 0 0 0 0 0 03020

121 11.21 0 0 0 0 0 0 0 20 0 0

122 11.21 0 0 0 0 0 0 0 10 1020

123 11.21 40 90 90 20 90 70 40 80 90 90

124 11.21 50 20 40 20 70 70 20 90 c 50

125 11.21 0 0 0 0 020 0 70 40 40

126 11.21 30 60 40 20 80 70 20 c 90 80

127 11.21 80 c c c c c c c c c

128 1.12 80 c 90 70 90 90 c c c c

129 11.21 40 70 60 90 80 80 c c c c

130 1.12 40 c 80 80 90 c 60 c c c TABLE 5 (continued)

PREEMERGENCE TESTS

% PLANT INHIBITION

Y A S D B M C V I W

e n e o y o o e n i Cpd. Rate n b j b g g b l a b

No. kg/ha a g g r r l u e u w

131 1.12 80 20 80 20 70 c 30 c 90 c

132 1. 12 0 30 80 c 80 80 30 c c c

133 1.12 10 20 90 40 10 80 30 c 80 c

134 1.12 c c 90 90 c 90 c c c c

135 1.12 c 10 80 10 c c 60 c c c

136 1.12 10 90 90 40 c c 20 c c c

137 11.21 90 c c c c c c c c c

138 11.21 0 0 0 0 0 0 0 80 20 70

139 11.21 20 90 80 90 80 90 90 c c c

140 11.21 80 60 c 20 c c c c c c

141 1.12 30 90 70 60 80 80 20 c 90 90

142 11.21 60 c 90 20 90 90 60 c c c

143 1.12 0 40 20 10 20 20 80 30 80 70

144 11.21 020 020 0 0 0 20 20 20

145 11.21 0 10 10 20 30 20 30 30 20 40

146 11.21 60 c c c c 80 30 c c c

147 11.21 60 c 90 70 c 80 20 c c 90

148 11.21 80 c c c c 90 50 c c c

149 11.21 0 0 0 0 0 50 20 70 60 80

150 11.21 0 0 0 0 0 0 0 0 0 0

151 11.21 30 90 90 30 90 c 80 c c c

152 11.21 0 0 0 0 0 0 0 0 0 0 TABLE 5 (continued)

PREEMERGENCE TESTS

% PLANT INHIBITION

Y A S D B M C V I W

e n e o y o o e n i

Cpd . Rate n b j b g g b l m b No. kg/ha a g g r r l u e u w

153 1.21 30 60 c 70 90 80 40 c c c

154 1. 12 70 c 80 80 90 c c c c c

155 1.12 80 c c 60 c c c c c c

156 1. 12 0 c 90 30 90 90 90 c c 80

157 1.12 70 c 90 c c c c c c c

158 1. 12 10 10 80 40 30 50 40 80 20 30

159 11.21 0 0 0 0 0 0 0 0 0 0

* Wibw-THIN.

^ Excessive damping off

# Observation ca. 4-weeks

POST-EMERGENCE HERBICIDE TESTS

The post-emergence herbicidal activity of some of the various compounds of this invention was demonstrated by greenhouse testing in the following manner. Topsoil is placed in aluminum pans having holes in the bottom and compacted to a depth of 0.95 to 1.27 cm from the top of the pan. A predetermined number of seeds of each of several dicotyledonous and monocotyledonous annual plant species and/or vegetative propagules for the perennial plant species are placed on the soil and pressed into the soil surface. The seeds and/or

vegetative propagules are covered with soil and leveled. The pans are then placed on a bench in the greenhouse and watered from belov as needed. After the plants reach the desired age (two to three weeks), each pan, is removed individually to a spraying chamber and sprayed by means of an atomizer, operating at a spray pressure of 170.3 kPa (10 psig) at the application rates noted. In the spray solution is an amount of an emulsifying agent mixture to give a spray solution or suspension which contains about 0.4% by volume of the emulsifier. The spray solution or suspension contains a sufficient amount of the candidate chemical in order to give application rates of the active ingredient corresponding to those shown in Table 2, while applying a total amount of solution or suspension equivalent to 1870 L/Ha (200 gallons/acre). The pans were returned to the greenhouse and watered as before and the injury to the plants as compared to the control is observed at approximately 10- 14 days (usually 11 days) and in some instances observed again at 24-28 days (usually 25 days) after spraying. The post-emergent herbicidal activity shown in Table 6 is the percent inhibition of each plant species. TABLE 6

POST-EMERGENCE TESTS % PLANT INHIBITION

Y A S D B M C V I W

e n e o y o o e n i Cpd. Rate n b j b g g b l m b

No. kg/ha s g g r r l u e u w

22 1.12 40 40 30 50 30 c c c 80 80

23 1.12 50 20 40 40 80 c c c 60 c

24 11.21 40 60 80 30 90 80 70 c 90 c

25 @ 11.21 10 0 10 0 0 20 20 30 40 90

26 11.21 0 0 10 0 0 20 20 20 30 0

27 11.21 0 0 0 0 10 30 10 90 50 70

28 11.21 20 10 10 0 10 80 c c 90 c

29 11.21 20 10 60 10 0 20 20 c 70 60

30 1.12 0 10 30 20 30 90 90 90 80 80

31 @ 11.21 0 20 20 0 20 80 80 c 50 60

32 11.21 40 90 90 c 90 c 90 c 90 c

33 11.21 30 90 c c c 90 c c c c

34 11.21 20 40 70 10 70 80 80 c 90 80

35 11.21 30 10 70 0 c c 80 c 8070

36 @ 11.21 20 20 50 30 40 60 60 c 70 c

37 11.21 30 80 90 90 c c c c c c

38 @ 11.21 20 60 70 0 70 c 60 c 60 60

39 11.21 30 80 80 20 90 c 50 c 90 80

40 1.12 40 90 90 c c 90 c c 90 90

41 1.12 10 10 70 80 c c 60 c 90 70

42 11.21 60 90 90 40 80 c c c c c

43 1.12 20 0 40 30 30 90 90 c 80 70 TABLE 6 (continued)

POST-EMERGENCE TESTS

% PLANT INHIBITION

Y A S D B M C V I W

e n e o y o o e n i

Cpd. Rate n b j b g g b l m b

No. kg/ha s g g r r l u e u w

44 11.21 40 c c c c c c c c c

45 11.21 30 90 c 90 c c c c c c

46 1.12 20 0 0 0 0 30 30 30 30 60

47 1.12 20 0 20 20 0 30 30 50 40 80

48 1.12 10 20 20 20 20 c 60 c 40 80

49 @ 1.12 0 10 0 0 0 40 30 50 40 60

50 11.21 20 30 90 50 50 70 60 90 c c

51 @ 11.21 0 20 40 20 50 90 c c 80 c

52 1.12 20 40 20 20 40 90 60 c 70 c

53 1.12 20 20 80 50 90 90 c c 80 90

54 1.12 0 20 40 20 10 30 40 70 60 60

55 1.12 30 10 40 20 80 c c c 70 c

56 @ 1.12 20 50 20 20 0 90 90 c 70 90

57 1.12 0 0 0 0 0 20 20 60 50 80

58 @ 1.12 20 10 20 0 30 c 90 c 70 c

59 @ 11.21 20 60 80 20 80 c 90 90 80 c

60 1.12 20 20 60 20 60 c c c 50 80

61 1.12 30 60 90 c c 60 c c 80 90

62 1.12 20 50 80 50 50 50 80 90 70 80

63 1.12 30 80 c c c c c 90 90 c

64 1.12 30 90 c c 90 c c c c c

65 1.12 30 60 80 90 90 c c 90 c 90 TABLE 6 (continued)

POST-EMERGENCE TESTS % PLANT INHIBITION

Y A S D B M C V I W

e n e o y o o e n i

Cpd. Rate n b j b g g b l a b No . kg/ha s g g r r l u e u w

66 1.12 30 60 80 50 40 c 80 c 50 c

67 1.12 30 70 70 80 70 90 90 c c c

68 1.12 30 40 90 50 30 60 60 90 60 40

69 1.12 40 50 50 90 70 c c c 70 c

70 1.12 20 30 20 20 20 c c c 80 70

71 1.12 20 90 90 90 80 c c 90 60 c

72 1.12 10 0 50 20 50 90 80 90 20 60

73 1.12 30 10 80 20 c 80 90 c 50 c

74 1.12 20 20 70 40 60 c c c 60 c

75 1.12 50 0 30 20 40 c c c 50 c

76 1.12 20 20 80 50 70 c c 90 60 80

77 1.12 20 20 60 30 60 c c 90 50 c

78 1.12 20 30 30 50 30 c 80 90 60 70

79 1.12 20 0 70 20 0 c 90 90 60 c

80 1.12 30 10 70 20 60 c c 90 80 90

81 1.12 10 c c c c 90 c c c c

82 1.12 20 20 30 0 0 80 80 C 40 30

83 1.12 1090 c c c c c 90 90 c

84 1.12 20 70 c 90 90 90 70 c 80 c

85 11.21 30 60 90 6090 c 90 90 90 c

86 1.12 10 30 20 30 20 60 50 c 50 90 TABLE 6 (continued)

POST-EMERGENCE TESTS % PLANT INHIBITION

Y A S D B M C V I W

e n e o y o o e n i

Cpd. Rate n b j b g g b l m b

No. kg/ha s g g r r l u e u w

87 1.12 10 40 80 c c c c c 90 90

88 1.12 20 70 80 c c c c c c 80

89 1.12 10 50 60 70 40 90 90 90 90 80

90 1.12 0 20 80 90 90 90 80 c 80 80

91 1. 12 10 40 90 90 90 80 c 90 90 80

92 1.12 40 70 70 80 30 c c c 90 40

93 11.21 0 0 20 10 70 80 80 c 90 70

94 11.21 10 20 0 0 0 20 80 70 60 40

95 11.21 10 20 20 0 0 20 30 c 90 c

96 11.21 10 20 90 50 90 60 30 c 40 c

97 11.21 0 0 0 0 0 20 30 60 30 80

98 11.21 0 0 0 0 0 10 10 0 0 0

99 11.21 0 0 0 0 0 0 0 30 0 0

100 11.21 0 0 20 020 0 0 30 10 20

101 11.21 0 0 20 0 0 30 20 20 0 40

102 11.21 0 10 20 10 30 20 10 30 20 60

103 11.21 0 0 0 0 0 0 0 0 0 60

+ 11.21 0 0 20 0 30 30 50 50 30 60

104 11.21 10 20 40 0 40 50 60 80 70 c

105 11.21 20 60 80 30 30 80 70 c 80 c

106 11.21 0 0 0 0 0 40 40 50 40 80

107 11.21 20 50 80 50 60 c c c c c TABLE 6 ( continued )

POST-EMERGENCE TESTS

% PLANT INHIBITION

Y A S D B M C V I W

e n e o y o o e n i

Cpd. Rate n b j b g g b l m b

No . kg/ha s g g r r l u e u w

108 11.21 30 30 60 20 30 60 50 90 50 c

109 11.21 30 30 40 20 40 30 30 90 50 c

110 11.21 30 70 80 40 50 50 70 c 70 c

111 11.21 0 40 20 0 10 20 10 70 80 50

112 11.21 20 60 90 40 50 40 70 c 80 c

113 1.12 0 0 10 0 10 10 10 20 0 90

114 11.21 0 0 0 0 0 0 30 20 0 40

115 11.21 30 30 c 90 90 90 c c c c

116 11.21 20 20 60 30 50 80 70 c 50 60

117 @ 11.21 10 50 50 40 80 60 50 c 90 c

118 11.21 0 0 0 0 0 20 0 20 10 0

119 11.21 10 0 0 0 0 0 0 0 0 0

120 11.21 0 0 0 0 0 0 0 10 0 0

121 11.21 0 0 0 0 0 20 20 0 0 0

122 11.21 0 0 0 0 0 20 0 20 0 20

123 11.21 0 20 0 0 0 20 50 60 20 c

124 11.21 0 0 0 0 0 0 0 30 20 20

125 11.21 0 0 0 0 0 0 0 20 0 0

126 11.21 0 0 0 0 0 20 20 40 20 50

127 11.21 10 90 90 70 c c 70 c c c

128 1.12 10 50 40 80 80 80 80 80 60 c

129 11.21 10 30 30 0 30 80 50 c 80 c TABLE 6 ( continued )

POST-EMERGENCE TESTS

% PLANT INHIBITION

Y A S D B M C V I W

e n e o y o o e n i

Cpd. Rate n b j b g g b l m b

No. kg/ha s g g r r l u e u w

130 1.12 30 60 40 50 20 c c c c c

131 1.12 40 20 60 20 70 c 90 c 40 80

132 1.12 30 30 40 80 80 c c c 80 80

133 1.12 10 40 40 80 90 90 90 c 40 40

134 1.12 0 90 80 c c c c c 80 50

135 1.12 20 10 80 0 60 c 80 c 50 50

136 1.12 10 20 60 30 20 80 80 c 90 90

137 11.21 20 c c c c c 90 c c c

138 11.21 0 0 20 0 0 40 30 40 20 c

139 11.21 10 30 80 30 20 50 40 c c c

140 11.21 20 10 80 10 70 60 50 c 70 70

141 1.12 0 90 90 80 70 80 70 c 70 70

142 11.21 10 20 80 20 10 40 30 80 30 70

143 1.12 20 90 90 c 70 c c c 90 50

144 11.21 0 20 0 20 0 20 20 30 20 50

145 @ 11.21 10 0 0 0 10 20 20 40 40 20

146 @ 11.21 10 70 80 90 90 60 60 c 80 c

147 11.21 0 60 80 30 80 80 70 c 90 c

148 11.21 10 40 40 0 20 20 30 c 90 c

149 @ 11.21 0 0 0 0 0 10 10 10 0 40

150 @ 11.21 0 0 0 0 0 20 0 0 0 20

151 11.21 10 0 0 0 0 60 60 80 60 c TABLE 6 ( continued)

POST-EMERGENCE TESTS % PLANT INHIBITION

Y A S D B M C V I W

e n e o y o o e n i Cpd . Rate n b j b g g b l m b

No. kg/ha s g g r r l u e u w

152 11.21 0 0 0 0 0 0 0 0 0 0

153 11.21 10 10 10 020 40 30 80 80 c

154 1.12 20 c 80 80 70 7080 c c 80

155 1.12 10 90 80 70 90 70 c c 90 30

156 1.12 10 80 c 30 50 90 40 C 90 70

157 1.12 20 90 90 90 90 c c c 90 80

158 1.12 10 70 70 60 40 c c c 70 50

159 11.21 0 0 0 0 0 20 10 10 0 0

@ Poor cocklebur response

+ Duplicate teat

The herbicidal compositions of this invention, including concentrates which require dilution prior to application, may contain at least one active ingredient and an adjuvant in liquid or solid form. The

compositions are prepared by admixing the active

ingredient with an adjuvant including diluents,

extenders, carriers, and conditioning agents to provide compositions in the form of finely-divided particulate solids, granules, pellets, solutions, dispersions or emulsions. Thus, it is believed that the active

ingredient could be used with an adjuvant such as a finely-divided solid, a liquid of organic origin, water, a vetting agent, a dispersing agent, an emulsifying agent or any suitable combination of these.

Suitable vetting agents are believed to include alkyl benzene and alkyl naphthalene sulfonates, sulfated fatty alcohols, amines or acid amides, long chain acid esters of sodium isothionate, esters of sodium sulfosuccinate, sulfated or sulfonated fatty acid esters, petroleum sulfonates, sulfonated vegetable oils, ditertiary acetylenic glycols, polyoxyethylene

derivatives of alkylphenols (particularly isooctylphenol and nonylphenol) and polyoxyethylene derivatives of the mono-higher fatty acid esters of hexitol anhydrides (e.g., sorbitan). Preferred dispersants are methyl cellulose, polyvinyl alcohol, sodium lignin sulfonates, polymeric alkyl naphthalene sulfonates, sodium

naphthalene sulfonate, and polymethylene bisnaphthalene sulfonate. Wettable povders are water-dispersible compositions containing one or more active ingredients, an inert solid extender and one or more wetting and dispersing agents. The inert sriid extenders are usually of mineral origin such as the natural clays, diatomaceous earth and synthetic minerals derived from silica and the like. Examples of such extenders include kaolinites, attapulgite clay and synthetic magnesium silicate. The vettable povders compositions of this invention usually contain from above 0.5 to 60 parts (preferably from 5-20 parts) of active ingredient, from about 0.25 to 25 parts (preferably 1-15 parts) of vetting agent, from about 0.25 to 25 parts (preferably 1.0-15 parts) of dispersant and from 5 to about 95 parts (preferably 5-50 parts) of inert solid extender, all parts being by weight of the total composition. Where required, from about 0.1 to 2.0 parts of the solid inert extender can be replaced by a corrosion inhibitor or anti-foaming agent or both.

Other formulations include dust concentrates comprising from 0.1 to 60% by weight of the active ingredient on a suitable extender; these dusts may be diluted for application at concentrations within the range of from about 0.1-10% by weight.

Aqueous suspensions or emulsions may be prepared by stirring a nonaqueous solution of a water-insoluble active ingredient and an emulsification agent with water until uniform and then homogenizing to give stable emulsion of very finely divided particles. The resulting concentrated aqueous suspension is characterized by its extremely small particle size, so that when diluted and sprayed, coverage is very uniform.

Suitable concentrations of these formulations contain from about 0.1-60%, preferably 5-50% by weight of active ingredient, the upper limit being determined by the solubility limit of active ingredient in the solvent. Concentrates are usually solutions of active ingredient in water-immiscible or partially water-immiscible solvents together with a surface active agent. Suitable solvents for the active ingredient of this invention include dimethylformamide, dimethylsulfoxide, N-methylpyrrolidone, hydrocarbons, and water-immiscible ethers, esters, or ketones. However, other high

strength liquid concentrates may be formulated by dissolving the active ingredient in a solvent then diluting, e.g., with kerosene, to spray concentration. The concentrate compositions herein generally contain from about 0.1 to 95 parts (preferably 5-60 parts) active ingredient, about 0.25 to 50 parts

(preferably 1-25 parts) surface active agent and where required about 5 to 94 parts solvent, all parts being by weight based on the total weight of emulsifiable oil.

Granules are physically stable particulate compositions comprising active ingredient adhering to or distributed through a basic matrix of an inert, finely-divided particulate extender. In order to aid. leaching of the active ingredient from the particulate extender, a surface active agent such as those listed hereinbefore can be present in the composition. Natural clays, pyrophyllites, illite, and vermiculite are examples of operable classes of particulate mineral extenders. The preferred extenders are the porous, absorptive,

preformed particles such as preformed and screened particulate attapulgite or heat expanded, particulate vermiculite and the finely-divided clays such as kaolin clays, hydrated attapulgite or bentonitic clays. These extenders are sprayed or blended with the active

ingredient to form the herbicidal granules.

The granular compositions of this invention may contain from about 0.1 to about 30 parts by weight of active ingredient per 100 parts by weight of clay and 0 to about 5 parts by weight of surface active agent per 100 parts by weight of particulate clay.

The compositions of this invention can also contain other additaments, for example, fertilizers, other herbicides, other pesticides, safeners and the like used as adjuvants or in combination with any of the above-described adjuvants. Chemicals useful in combination with the active ingredients of this invention included, for example, triazines, ureas, sulfonylureas, carbamates, acetamides, acetanilides, uracils, acetic acid or phenol derivatives, thiolcarbamates, triazoles, benzoic acid derivatives, nitriles, heterophenyl ethers, nitrophenyl ethers, diphenyl ethers, pyridines and the like such as:

Heterocyclic Nitroσen/Sulfur Derivatives 2-Chloro-4-ethylamino-6-isopropylamino-a-triazine

2-Chloro-4,6-bis(isopropylamino)-s-triazine

2-Chloro-4,6-bis(ethylamino)-a-triazine

3-Isopropyl-1H-2,1,3-benzothiadiazin-4-(3H)-one 2,2- dioxide

3-Amino-1,2,4-triazole

6,7-Dihydrodipyrido(1,2-:2',1'-c)-pyrazidiinium salt 5-Bromo-3-isopropyl-6-methyluracil

1,1'-Dimethyl-4,4'-bypyridinium

2-(4-Isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-3- quinolinecarboxylie acid

Isopropylamine salt of 2-(4-isopropyl-4-methyl-5- oxo-2-imidazolin-2-yl)nicotinic acid

Methyl 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2- yl)-m-toluate and methyl 2-(4-isopropyl-4-methyl- 5-oxo-2-imidazolin-2-yl)-p-toluate

5-(Trifluoromethyl)-4-chloro-3-(3'-[1-ethoxycarbonyl]- ethoxy-4'-nitrophenoxy)-1-methylpyrazol;

5-(Trifluoromethyl)-4-chloro-3-(3'-methoxy-4'-nitro¬phenoxy)-1-methylpyrazole;

5-(Trifluoromethyl)-4-chloro-3-(3'-[1-butoxycarbonyl]-ethoxy-4'-nitrophenoxy)-4-methylpyrazol;

5-(Trifluoromethyl)-4-chloro-3-(3'-methylsulfamoylcarbonyl propoxy-4'-nitrophenoxy)-4-methylpyrazol;

5-(Trifluoromethyl)-4-chloro-3-(3'-propoxycarbonylmethyloxime-4'-nitrophenoxy)-1-methylpyrazole;

(+)-2-[4-[[5-(Trifluoromethyl)-2-pyridinyl]oxy]phenoxy]- propanoic acid (9CI).

S,S-dimethyl-2-(difluoromethyl)-4-isobutyl-6-trifluoromethyl-3,5-pyridinedicarbothioate;

3-Pyridinecarboxylic Acid, 2-(difluoromethyl)-5-(4,5- dihydro-2-thiazolyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-, methyl ester;

3,5-Pyridinedicarboxylic acid, 2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-, dimethyl ester; 3,5-Pyridinedicarbothioic acid, 4-(cyclopropylmethyl)-2- (difluoromethyl)-6-(trifluoromethyl)-, S,S-dimethyl ester;

Sulf oximine, N-(diethoxyphosphinyl)-S-methyl-S-phenyl-

Ureas and Sulfonylureas

N-(4-Chlorophenoxy) pheny 1-N,N-dimethylurea

N,N-dimethyl-N'-(3-chloro-4-methylphenyl) urea

3-(3,4-dichlorophenyl)-1,1-dimethylurea

1,3-Dimethyl-3-(2-benzothiazolyl) urea

3-(p-Chlorophenyl)-1,1-dimethylurea

1-Butyl-3-(3,4-dichlorophenyl)-1-methylurea

2-Chloro-N[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)

aminocarbonyl]-benzenesulf onamide

Methyl 2-(((((4,6-dimethyl-2-pyrimidinyl) amino)- carbonyl) amino) sulf onyl) benzoate

Ethyl 1-[methyl 2-(((((4,6-dimethyl-2-pyrimidinyl)- amino) carbonyl) amino) sulf onyl)] benzoate

Methy 1-2 ((4,6-dimethoxy pyrimidin-2-yl) aminocarbonyl) amino sulf onyl methyl) benzoate

Methyl 2-(((((4-methoxy-6-methyl-1,3,5-triazin-2-yl)- amino) carbonyl) amino) sulfonyl) benzoate

N-[3-(N,N-dimethylcarbamoyl)-2-pyridin-2-yl] sulfonyl- N'-(4,6-dimethoxypyrimidin-2-yl) urea

N-[(3-ethylsulfonyl)-2-pyridin-2-yl]-sulfonyl-N'-(4,6- dimethoxy-pyrimidin-2-yl) urea

N-(2-methoxycarbonylphenyl sulfonyl)-N'-(4,6-bis- difluoromethoxypyrimidin-2-yl) urea

Carbamates/Thiolcarbamates

2-Chloroallyl diethyldithiocarbamate

S-(4-chlorobenzyl) N,N-diethylthiolcarbamate

Isopropyl N-(3-chlorophenyl) carbamate

S-2,3-dichloroallyl N, N-diisopropylthiolcarbamate

S-N,N-dipropylthiolcarbamate

S-propyl N,N-dipropylthiolcarbamate

S-2,3,3-trichloroallyl-N,N-diisopropylthiolcarbamate Acetamides/Acetanilldes/Anilines/Amides

2-Chloro-N,N-diallylacetamide

N,N-dimethyl-2,2-diphenylacetamide

N-(2,4-dimethylthien-3-yl)-N-(l-methoxyprop-2-yl)-2- chloroacetamide

N-(1H-pyrazol-1-ylmethyl-N-(2,4-dimethylthien-3-yl)-2- chloroacetamide

N-(1-pyrazol-1-ylmethyl)-N-(4,6-dimethoxypyrimidin-5- yl)-2-chloroacetamide

N-(2,4-dimethyl-5-[[[(trifluoromethyl)sulfonyl]amino]- phenyl]acetamide

N-Isopropyl-2-chloroacetanilide

N-Isopropyl-1-(3,5,5-trimethylcyclohexen-1-yl)-2- chloroacetamide

2',6'-Diethyl-N-(butoxymethyl)-2-chloroacetanilide

2',6'-Diethyl-N-(2-n-propoxyethyl)-2-chloroacetanilide 2',6'-Dimethyl-N-(l-pyrazol-1-ylmethyl)-2-chloroacetanilide

2',6'-Diethyl-N-methoxymethyl-2-chloroacetanilide 2,-Methyl-6'-ethyl-N-(2-methoxyprop-2-yl)-2-chloroacetanilide

2•-Methyl-6'-ethyl-N-(ethoxymethyl)-2-chloroacetanilide

α , α ,α-Trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine N-(l,l-dimethylpropynyl)-3,5-dichlorobenzaaιide

Acids/Esters/Alcohols

2,2-Dichloropropionic acid

2-Methy1-4-chlorophenoxyacetic acid

2,4-Dichlorophenoxyacetic acid

Methyl-2-[4-(2,4-dichlorophenoxy)phenoxy]propionate 3-Amino-2,5-dichlorobenzoic acid

2-Methoxy-3,6-dichlorobenzoic acid

2 , 3 , 6-Trichlorophenylacetic acid

N-1-naphthylphthalamic acid

Sodium 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2- nitrobenzoate

4,6-Dinitro-o-sec-butylphenol

N-(phosphonomethyl)glycine and its salts Butyl (R)-2-[4-[(5-(trifluoromethyl)-2-pyridinyl)oxy]- phenoxy] propanoate

Ethers

2,4-Dichlorophenol-4-nitrophenyl ether

2-Chloro-δ,δ,δ-trifluoro-p-tolyl-3-ethoxy-4-nitrodiphenyl ether

5-(2-chloro-4-trifluoromethylphenoxy)-N-methylsulfonyl 2-nitrobenazmide

1'-(Carboethoxy) ethyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoate

Miscellaneous

2,6-Dichlorobenzonitrile

Monosodium acid methanearsonate

Disodium methanearsonate

2-(2-chlorophenyl)methyl-4,4-dimethyl-3-isoxazolidinone

7-Oxabicyclo (2.2.1) heptane, 1-methyl-4-(1-methylethyl)-2-(2-methylphenylmethoxy)-, exo- Glyphosate and salts thereof.

Fertilizers useful in combination with the active ingredients include, for example, ammonium nitrate, urea, potash and superphosphate. Other useful additaments include materials in which plant organisms take root and grow such as compost, manure, humus, sand and the like.

Herbicidal formulations of the types described above are exemplified in several illustrative

embodiments below.

I. Emulsifiable Concentrates

Weight Percent

A. Compound No. 22 4.0

Free acid of complex organic phosphate

or aromatic or aliphatic hydrophobe

base (e.g., GAFAC RE-610, registered

trademark of GAF Corp.) 3.5

Polyoxyethylene/polyoxypropylene block

copolymer with butanol (e.g., Tergitol XH,

registered trademark of Union Carbide

Corp.) 1.5 Xylene 5.34

Monochlorobenzene 85.66

100.00

B. Compound No. 36 3.0

Free acid of complex organic phosphate

of aromatic or aliphatic hydrophobe

base (e.g., GAFAC RE-610) 4.0 Polyoxyethylene/polyoxypropylene block

copolymer with butanol (e.g., Tergitol XH) 1.60

Xylene 4.75 Monochlorobenzene 86.65

100.00

C. Compound No. 43 2.5

Free acid of complex organic phosphate

or aromatic or aliphatic hydrophobe

base (e.g., GAFAC RE-610, registered

trademark of GAF Corp.) 4.0

Polyoxyethylene/polyoxypropylene block

copolymer with butanol (e.g., Tergitol XH,

registered trademark of Union Carbide

Corp.) 1.5

Cyclohexanone 5.5

Aromatic 200 86.5

100.00 Weight Percent

D. Compound of No. 52 5.0

Free acid of complex organic phosphate

of aromatic or aliphatic hydrophobe

base (e.g., GAFAC RE-610 3.00

Polyoxyethylene/polyoxypropylene block

copolymer with butanol (e.g., Tergitol XH) 2 . 0 Phenol 5 . 0 Monochlorobenzene 85 . 0

100 .00

E. Compound No. 53 1 .50

Free acid of complex organic phosphate

or aromatic or aliphatic hydrophobe

base (e.g., GAFAC RE-610, registered

trademark of GAF Corp.) 4.50 Polyoxyethylene/polyoxypropylene block

copolymer with butanol (e.g., Tergitol XH,

registered trademark of Union Carbide

Corp.) 1.00 Isophorone 5.34

Emerset 2301 87.66

100.00

F. compound No. 54 4.50

Free acid of complex organic phosphate

of aromatic or aliphatic hydrophobe

base (e.g., GAFAC RE-610 3.00 Polyoxyethylene/polyoxypropylene block

copolymer with butanol (e.g., Tergitol XH) 2.00

Cyslohexanone 4.75 7-Butyrolactone 85.75

100.00 Weight Percent

II. Flowables

A. Compound No. 58 25.0

Xanthan Gum 0.3

Ethylene Glycol 10.0

Sodium lignosulfonate 3.5

Sodium N-methyl-N-oleyl taurate 1.0

Water 60.2

100.00 B. Compound No. 59 45.0

Xanthan Gum 0.2

Magnesium Aluminum Silicate 0.2

Alkyl aryl sulfonate 3.5

Propylene glycol 7.0

Water 44.1

100.00 C. Compound No. 66 23.0

Xanthan gum 0.3

Propylene Glycol 10.0

Sodium lignosulfonate 3.5

Alkyl aryl sulfonate (e.g., Morwet D-425) 2.0

Water 61.2

100.00 D. Compound No. 81 45.0

Magnesium Aluminum Silicate 0.3

Ethylene Glycol 7.0

Alkyl aryl sulfonate 3.5

EO/PO Block Copolymer (e.g., Pluronic

P-104) 1.0

Water 43.2

100.00 weight Percent

III. Wettable Powders

A. Compound No. 83 25.0

Sodium lignosulfonate 5.0 Kaolin 60.0

Amorphous silica (synthetic) 10.0

100.0

B. Compound No. 85 80.0

Sodium dioctyl sulfosuccinate 1.5 Alkyl Aryl Sulfonate 3.5

Kaolin 5.0

Amorphous silica (synthetic) 10.0

100.0

C. Compound No. 93 10.0

Sodium lignosulfonate 3.0

Sodium N-methyl-N-oleyl-taurate l.o

Amorphous silica (synthetic) 10.0

Kaolinite clay 76.0

100.0 D. Compound No. 96 30.0

Sodium lignosulfonate 4.0

Sodium dioctyl sulfosuccinate 1.0

Attapulgite clay 60.0

Amorphous silica (synthetic) 5.0

100.0

E. Compoud No. 102 75.0

Sodium dioctyl sulfosuccinate 1.25 Sodium lignosulfonate 3.0 Kaolin 10.75 Amorphous silica synthetic 10.0

100.0

F. Compound No. 106 15.0

Sodium lignosulfonate 3.0 Sodium N-methyl-N-oleyl-taurate 1.0 Amorphous silica (synthetic 10.0

Kaolinite clay 71.0

100.0 TV. Granules

Weight Percent

A. Compound No. 36 15. 0

Dipropylene Glycol 5. 0 Granular attapulgite (24/48 mesh) 80. 0

100. 0

B. Compound No. 43 5. 0

Ethylene Glycol (24/48 mesh) 15. 0 Granular Montmorillonite 80.0

100. 0

C. compound No. 49 1.0

Ethylene glycol 5.00

Granular Pyrophyllite (24/48 mesh) 94.0

100.0

D. Compound No. 52 5 . 0

Dipropylene Glycol 15.0

Granular Pyrophyllite (24/48 mesh) 80.0

100.0

E. Compound No. 53 20.0

Granular Bentonite (24/48 mesh) 80,0

100.0

F. Compound No. 54 20 .0

Amorphous silica (synthetic) 1 .0 Granular Montmorillonite (24/48 mesh) 79 .0

100 .0

G. Compound No. 58 5, .0

Ethylene glycol 10 .0

Granular Montmorillonite (24/48 mesh) 85.0

100 .0 H. Compound No. 59 10 .0

Dipropylene Glycol 10 .0

Granular Bentonite (30/60 mesh) 80 .0

100 .0 Weight Percent V. Suspension Concentrates

A. Compound No. 66 32.5

Sodium Naphthalene-Formaldehyde Condensate

(Morvet D-425) 3.0

Propylene Glycol 10.0 Sodium Diisopropyl Naphthalene Sulfonate

(Morvet IP) 1.0

Xanthan Gum (Kelzan S) 0.2 Water 52.3

100.0

B. Compound No. 81 37.0

Sodium Lignin Sulfonate (Polyfon H) 5.0 EO/PO Block Copolymer (Pluronic P-105) 2.0 Propylene Glycol 10.0

Xanthan Gum 0.2 water 45.8

100.0

C. Compound No. 83 25.0

Sodium Lignin Sulfonate (Polyfon H) 4.0

Sodium N-Methyl-N-oleyltaurate

(Igepon T-77) 1.0

Ethylene Glycol 10.0

Xanthan Gum (Rhodopol MD50) 0.2 Magnesium Aluminum Silicate (Van Gel-B) 0.2 water 59.6

100.0

D. Compound No. 85 30.0

Sodium naphthalene sulfonate formaldehyde

condensate 5.0

Glycerine 8.0

Methyl Cellulose (Methocel A15C) 0.3

Magnesium Aluminum Silicate (Van Gel B) 0.2

Water 56.5

100.0 Weight PercentE. Compound No. 93 33.0

Nonylphenol ethoxylate 9.5 mole EO

Sterox NJ 1.0

Sodium lignosulfonate (Reax 88B) 4.0

Ethylene Glycol 10.0

Xanthan Gum 0.2

Water 51.8

100.0 F. Compound No. 96 34.0

Sodium lignin sulfonate (Polyfon F) 10.0

Ethylene Glycol 10.0

Xanthan Gum 0.1

Water 45.9

100.0

G. Compound No. 102 30.0

Sodium Naphthalene Sulfonate formaldehyde

Condensate 10.0

Propylene Glycol 7.0

Snelling Grade Bentonite 0.5

Antifoam 0.5

Water 52.0

100.0

VI Microcapsules

(Active ingredient encapsulated within polymeric shell wall)

A. Compound No. 69 4.0

Polyurea shell wall 0.4

Reaxe 88B (dispersant) 1.0

NaCl (electrolyte) 5.0 water 89,6

100.00 Weight Percent

B. Compound No. 81 0.5

Polyurea shell wall 6.82 Reax^® C-21 (dispersant) 1.0 NaNO₃ (electrolyte) 5.0 Aromatic 200 (solvent) 45.0 Water 41.68

100.00

C. Compound No. 130 1.0

Polyurea shell vail 7.0 Reax^® c-21 2.0

NaCl 10.0

Xylene 40.0

Water 40.0

100.0

D. Compound No. 63 48.0

Polyurea shell vail 4.8 Reax^® 88B 3.0

NaCl 15.0 Kerosene 29.2

100.0

E. Compound No. 74 40.0

Polyurea shell vail 6.5 Reax^® 88B 2.0

NaNO₃ 10.5

Solvent 25.0

Water 16.0

100.0

F. Compound No. 157 10.0

Polyurea shell vail 8.5 Reax^® c-21 1.5

NaCl 6.0

Solvent 20.0

Water 54,0

100.0 When operating in accordance with the present invention, effective amounts of the compounds of this invention are applied to the soil containing the seeds, or vegetative propagules or may be incorporated into the soil media in any convenient fashion. The application of liquid and particulate solid compositions to the soil can be carried out by conventional methods, e.g., power dusters, boom and hand sprayers and spray dusters. The compositions can also be applied from airplanes as a dust or a spray because of their effectiveness at low dosages. The exact amount of active ingredient to be employed is dependent upon various factors, including the plant species and stage of development thereof, the type and condition of soil, the amount of rainfall and the specific compounds employed. In selective preemergence, post-emergence and soil applications a dosage of from about 0.0005 kg/ha (0.5 g/ha) to about 11.2 kg/ha is usually employed. A dosage of about 0.001 kg/ha (1.0 g/ha) to about 0.50 kg/ha (500 g/ha) is preferred. Lower or higher rates may be required in some instances. One skilled in the art can readily determine from this specification, including the above examples, the optimum rate to be applied in any

particular case.

The term "soil" is employed in its broadest sense to be inclusive of all conventional "soils" as defined in Webster's New International Dictionary.

Second Edition, Unabridged (1961). Thus, the term refers to any substance or medium in which vegetation say take root and grow, and includes not only earth but also compost, manure, muck, humus, loam, silt, mire, clay, sand, and the like, adapted to support plant growth.

Although this invention has been described with respect to specific embodiments, the details of these embodiments are not to be construed as limits- tions. Various equivalents, changes and modifications may be made without departing from the spirit and scope of this invention, and it is understood that such equivalent embodiments are part of this invention.

Claims (33)

WE CLAIM

1. compounds according to Formula I:

wherein

R₁ is hydrogen, C_1-5 alkyl optionally substituted with an R₄ member; C_3-8 cycloalkyl or cycloalkenyl optionally substituted with C_1-4 alkyl;

R₂ is C_1-5 alkyl optionally substituted with an R₄ member;

R₃ is hydrogen or halogen and

R₄ is hydrogen, C_1-8 alkyl, haloalkyl, alkylthio, alkoxyalkyl or polyalkoxyalkyl, C_3-8 cycloalkyl, cycloalkenyl, eyeloaIkyalkyl or cycloalkenylalkyl; C_2-8 alkenyl or alkynyl; carbamyl, halogen, amino, nitro, cyano, hydroxy, C_4-10 heterocycle containing 1-40, S (O) _m and/or N hetero atoms, C_6-12 aryl, aralkyl or alkaryl, -CXYR₈, -CXR₉, -CH₂OCOR₁₀, -YR₁₁, -NR₁₂R₁₃, or any two R₄ members may be combined through a saturated and/or unsaturated carbon, and/or hetero atom linkage to form a heterocyclic ring having up to 9 ring members, which may be substituted with any of said R₄ members or where not self-inclusive said R₄ or R_8-13 members substituted with any of said R₄ members; provided that when said two R₄ members are combined through a -hetero atom linkage, said heterocyclic ring has at least six ring members;

X is O, S(O)_m, NR₁₄ or CR₁₅R₁₆;

Y is O or S(O)_m or NR₁₇;

R₈-R₁₇ are one of said R₄ members;

m is 0-2 and

n is 0-5.

2. compounds according to Formula II

wherein

R₁, R₂ and R₃ are as defined for Formula I;

R₅ is independently one of said R₃ members and

R₆ and R₇ are independently one of said R₄ members or are combined to form a heterocyclic ring having up to 9 members and containing O, N and/or S atoms, which ring may be substituted with alkyl,

haloalkyl, alkoxy, alkenyl or alkynyl radicals each having up to 4 carbon atoms; provided that when said two R₆ and R₇ members are combined through a -hetero atom linkage, said heterocyclic ring has at least six ring members.

3. Compounds according to Formula III

wherein

R₁ and R₂ are C_1-5 alkyl;

R₃ and R₅ are hydrogen, bromo, chloro or fluoro; R₆ is an R₅ member or nitro;

R₇ is an R₄ member or

R₆ and R₇ are combined through an -OCH₂(C=O)-N- (R₄)-linkage to form a fused six-membered ring.

4. compounds according to Claim 3 wherein R₁ and R₂ are methyl;

R₃ is hydrogen, bromo or chloro;

R₅ is chloro or fluoro;

R₆ is chloro, fluoro, or nitro;

R₇ is a YR₁₁ member as defined in Formula I or

R₆ and R₇ are combined through an -OCH₂(C=O)-N-(propynyl)-linkage to give a fused 6-membered ring.

5. Compounds according to Claim 1 selected from the group consisting of

4-Chloro-3-(2-fluoro-4-chloro-5-(2-propynyloxy)phenyl)- 1-methyl-5-(methylsulfonyl)-1H-pyrazole

4-Bromo-3-(2-fluoro-4-chloro-5-(2-propynyloxy)phenyl)- 1-methyl-5-(methylsulfonyl)-1H-pyrazole

4-Chloro-3-(2-fluoro-4-chloro-5-(2-methoxyethoxy)- phenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole 4-Bromo-3-(2-fluoro-4-chloro-5-(2-methoxyethoxy)- phenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole 6-(4-Chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3- yl)-7-fluoro-4-(2-propynyl)-2H-1,4-benzoxazin-3- (4H)-one

(5-(4-Bromo-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3- yl)-2-chloro-4-fluorophenoxy)acetic acid, 1- methylethyl ester

(5-(4-Chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3- yl)-2-chloro-4-fluorophenoxy)acetic acid, 1- methylethyl ester

2-(5-(4-Bromo-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3- yl)-2-chloro-4-fluorophenoxy)propanoic acid,

ethyl ester and

2-(5-(4-Chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol- 3-yl)-2-chloro-4-fluorophenoxy)propanoic acid, ethyl ester.

6. 4-Chloro-3-(2-fluoro-4-chloro-5-(2- propynyloxy)phenyl) -1-methyl-5-(methylsulfonyl) -1H- pyrazole.

7. 4-Bromo-3- (2-fluoro-4-chloro-5- (2- propynyloxy)phenyl)-1-methyl-5-(methylsulfonyl)-1H- pyrazole.

8. 2- (5-(4-Chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl)-2-chloro-4-fluorophenoxy)- propanoic acid, ethyl ester.

9. (5-(4-Chloro-1-methyl-5-(methylsulfonyl)- 1H-pyrazol-3-yl)-2-chloro-4-fluorophenoxy)acetic acid, 1-methylethyl ester.

10. Herbicidal composition comprising an adjuvant and a herbicidally effective amount of a compound according to Formula I:

wherein

R₁ is hydrogen, C_1-5 alkyl optionally substituted with an R₄ member; C_3-8 cycloalkyl or cycloalkenyl optionally substituted with C_1-4 alkyl;

R₂ is C_1-5 alkyl optionally substituted with an

R₄ member;

R₅ is hydrogen or halogen and

R₄ is hydrogen, C_1-8 alkyl, haloalkyl, alkyl- thio, alkoxyalkyl or polyalkoxyalkyl, C_3-8 cycloalkyl, cycloalkenyl, cycloalkyalkyl or cycloalkenylalkyl; C_2-8 alkenyl or alkynyl; carbamyl, halogen, amino, nitro, cyano, hydroxy, C_4-10 heterocycle containing 1-4 O, S(O)_m and/or N hetero atoms, C_6-12 aryl, aralkyl or alkaryl, -CXYR₈, -CXR₉, -CH₂OCOR₁₀, -YR₁₁, -NR₁₂R₁₃, or any two R₄ members may be combined through a saturated and/or unsaturated carbon, and/or hetero atom linkage to form a heterocyclic ring having up to 9 ring members, which may be substituted with any of said R₄ members or where not self-inclusive said R₄ or R_8-13 members

substituted with any of said R₄ members; provided that when said two R₄ members are combined through a -hetero atom linkage, said heterocyclic ring has at least six ring members;

X is O , S (O)_m, NR₁₄ or CR₁₅R₁₆;

Y is O or S (O) _m or NR₁₇;

R₈-R₁₇ are one of said R₄ members;

m is 0-2 and

n is 0-5.

11. Herbicidal composition comprising an adjuvant and a herbicidally-effective amount of a compound according to Formula II:

wherein

R₁, R₂ and R₃ are as defined for Formula I;

R₅ is independently one of said R₃ members and

R₆ and R₇ are independently one of said R₄ members or are combined to form a heterocyclic ring having up to 9 members and containing O, N and/or S atoms, which ring may be substituted with alkyl, haloalkyl, alkoxy, alkenyl or alkynyl radicals each having up to 4 carbon atoms; provided that when said two R₆ and R₇ members are combined through a -hetero atom linkage, said heterocyclic ring has at least six ring members.

12. Herbicidal compositions comprising an adjuvant and a herbicidally-effective amount of a compound according to Formula III:

wherein

R₁ and R₂ are C_1-5 alkyl;

R₃ and R₅ are hydrogen, bromo, chloro or fluoro;

R₆ is an R₅ member or nitro;

R₇ is an R₄ member or

R₆ and R₇ are combined through an -OCH₂(C=O)- N-(R₄)-linkage to form a fused six-membered ring.

13. Composition according to Claim 12 wherein in said compound:

R₁ and R₂ are methyl;

R₃ is hydrogen, bromo or chloro;

R₅ is chloro or fluoro;

R₆ is chloro, fluoro or nitro;

R₇ is a YR₁₁ member as defined in Formula I or

R₆ and R₇ are combined through an 0CH₂(C=O)- N-(propynyl)-linkage to give a fused 6-membered ring.

14. Composition according to Claim 10 wherein said compound is selected from the group consisting of 4-Chloro-3-(2-fluoro-4-chloro-5-(2-propynyloxy)phenyl)- 1-methyl-5-(methylsulfonyl)-1H-pyrazole

4-Bromo-3-(2-fluoro-4-chloro-5-(2-propynyloxy)phenyl)- 1-methyl-5-(methylsulfonyl)-1H-pyrazole

4-Chloro-3-(2-fluoro-4-chloro-5-(2-methoxyethoxy)- phenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole 4-Bromo-3- (2-fluoro-4-chloro-5- (2-methoxyethoxy) - phenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole 6-(4-Chloro-1-methy1-5-(methylsulfonyl)-1H-pyrazol-3- yl)-7-fluoro-4-(2-propynyl)-2H-l,4-benzoxazin-3- (4H)-one

(5-(4-Bromo-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3- yl)-2-chloro-4-fluorophenoxy) acetic acid, 1- methylethyl ester

(5- (4-Chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3- yl)-2-chloro-4-fluorophenoxy) acetic acid, 1- methylethyl ester

2-(5-(4-Bromo-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3- yl)-2-chloro-4-fluorophenoxy)propanoic acid,

ethyl ester and

2-(5-(4-chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol- 3-yl)-2-chloro-4-fluorophenoxy)propanoic acid, ethyl ester.

15. Herbicidal composition comprising an adjuvant and a herbicidally-effective amount of 4-chloro-3-[1-fluoro-4-chloro-5-(2-propynyloxy)phenyl-1-methyl-5-(methylsulfonyl)-1H-pyrazole.

16. Herbicidal composition comprising an adjuvant and a herbicidally-effective amount of 4-Bromo-3-(2-fluoro-4-chloro-5-(2-propynyloxy)phenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole.

17. Herbicidal composition comprising an adjuvant and a herbicidally-effective amount of 2-(5-(4-Chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl)-2-chloro-4-fluorophenoxy)-propanoic acid, ethyl ester.

18. Herbicidal composition comprising an adjuvant and a herbicidally-effective amount of (5-(4-Chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3-yl)-2-chloro-4-fluorophenoxy)acetic acid, 1 methylethyl ester.

19. Method for combatting undesirable plants in crops which comprises applying to the locus thereof a herbicidally effective amount of a compound according to Formula I:

wherein

R₁ is hydrogen, C_1-5 alkyl optionally substituted with an R₄ member; C_3-8 cycloalkyl or cycloalkenyl optionally substituted with C,.₄ alkyl;

R₂ is C_1-5 alkyl optionally substituted with an R₄ member;

R₃ is hydrogen or halogen and

R₄ is hydrogen, C_1-8 alkyl, haloalkyl, alkylthio, alkoxyalkyl or polyalkoxyalky1, C_3-8 cycloalkyl, cycloalkenyl, cycloalkyalkyl or cycloalkenylalkyl; C_2-8 alkenyl or alkynyl; carbamyl, halogen, amino, nitro, cyano, hydroxy, C_4-10 heterocycle containing 1-4 o, S(O)_R and/or N hetero atoms, C_6-12 aryl, aralkyl or alkaryl, -CXYR₈, -CXR₉, -CH₂OCOR₁₀, -YR₁₁, -NR₁₂R₁₃, or any two R₄ members may be combined through a saturated and/or unsaturated carbon, and/or hetero atom linkage to form a heterocyclic ring having up to 9 ring members, which may be substituted with any of said R₄ members or where not self-inclusive said R₄ or R_8-13 members

substituted with any of said R₄ members; provided that when said two R₄ members are combined through a -hetero atom linkage, said heterocyclic ring has at least six ring members;

X is O, S(O)_m, NR₁₄ or CR₁₅R₁₄;

Y is O or S(O). or NR₁₇;

R₈-R₁₇ are one of said R₄ members;

m is 0-2 and

n is 0-5.

20. Method for combatting undesirable plants in crops vhich comprises applying to the locus thereof a herbicidally-effective amount of a compound according to Formula II :

wherein

R₁, R₂ and R₃ are as defined for Formula I;

R₅ is independently one of said R₃ members and R₆ and R₇ are independently one of said R₄ members or are combined to form a heterocyclic ring having up to 9 members and containing O, N and/or S atoms, which ring may be substituted with alkyl, haloalkyl, alkoxy, alkenyl or alkynyl radicals each having up to 4 carbon atoms; provided that when said two R₆ and R₇ members are combined through a -hetero atom o

linkage, said heterocyclic ring has at least six ring members.

21. Method of combatting undesirable plants in crops vhich comprises applying to the locus thereof a herbicidally-effective amount of a compound according to Formula III:

wherein R₁ and R₂ are C_1-5 alkyl;

R₃ and R₅ are hydrogen, bromo, chloro or fluoro; R₆ is an R₅ member or nitro;

R₇ is an R₄ member or

R₆ and R₇ are combined through an -OCH₂(C=O)-N- (R₄)-linkage to form a fused six-membered ring.

22. Method according to Claim 21 wherein in said compound:

R₁ and R₂ are methyl;

R₃ is hydrogen, bromo or chloro;

R₅ is chloro or fluoro;

R₆ is chloro, fluoro, or nitro;

R₇ is a YR₁₁ member as defined in Formula I or R₆ and R₇ are combined through an -OCH₂(C=O)- N-(propynyl)-linkage to give a fused 6-membered ring.

23. Method according to Claim 19 wherein said compound is selected from the group consisting of

4-Chloro-3-(2-fluoro-4-chloro-5-(2-propynyloxy)phenyl)- 1-methyl-5-(methylsulfonyl)-1H-pyrazole

4-Bromo-3-(2-fluoro-4-chloro-5-(2-propynyloxy)phenyl)- 1-methyl-5-(methylsulfonyl)-1H-pyrazole

4-Chloro-3-(2-fluoro-4-chloro-5-(2-methoxyethoxy)- phenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole 4-Bromo-3-(2-fluoro-4-chloro-5-(2-methoxyethoxy)- phenyl)-1-methyl-5-(methylsulfonyl)-1H-pyrazole 6-(4-Chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3- yl)-7-fluoro-4-(2-propynyl)-2H-l,4-benzoxazin-3- (4H)-one

(5-(4-Bromo-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3- yl)-2-chloro-4-fluorophenoxy)acetic acid, 1- methylethyl ester

(5-(4-Chloro-1-methyl-5-(methylsulfonys)-1H-pyrazol-3- yl)-2-chloro-4-fluorophenoxy)acetic acid, 1- methylethyl ester 2-(5-(4-Bromo-1-methyl-5-(methylsulfonyl)-1H-pyrazol-3- yl)-2-chloro-4-fluorophenoxy)propanoic acid, ethyl ester

2-(5-(4-Chloro-1-methyl-5-(methylsulfonyl)-1H-pyrazol- 3-yl)-2-chloro-4-fluorophenoxy)propanoic acid, ethyl ester.

24. Method of combatting undesirable plants in crops which comprises applying to the locus thereof a herbicidally-effective amount of 4-chloro-3-[2-fluoro- 4-chloro-5-(2-propynyloxy)phenyl]-1-methyl-5-(methylsulfonyl)-1H-pyrazole.

25. Process for the preparation of compounds according to Formula I which comprises reacting a compound according to Formula B with an oxidizing agent according to the equation

wherein

R₁ is hydrogen, C_1-5 alkyl optionally substituted with an R₄ member; C_3-8 cycloalkyl or cycloalkenyl optionally substituted with C_1-4 alkyl;

R₂ is C_1-5 alkyl optionally substituted with an R₄ member;

R₃ is hydrogen or halogen and

R₄ is hydrogen, C_1-8 alkyl, haloalkyl, alkylthio, alkoxyalkyl or polyalkoxyalky1, C_3-8 cycloalkyl, cycloalkenyl, cycloalkyalkyl or cycloalkenylalkyl; C_2-8 alkenyl or alkynyl; carbamyl, halogen, amino, nitro, cyano, hydroxy, C_4-10 heterocycle containing 1-40, S(O)_m and/or N hetero atoms, C_6-12 aryl, aralkyl or alkaryl, -CXYR₈, -CXR₉, -CH₂OCOR₁₀, -YR₁₁, -NR₁₂R₁₃, or any two R₄ members may be combined through a saturated and/or unsaturated carbon, and/or hetero atom linkage to form a heterocyclic ring having up to 9 ring members, which may be substituted with any of said R₄ members or where not self-inclusive said R₄ or R_8-13 members

substituted with any of said R₄ members; provided that when said two R₄ members are combined through a -hetero atom linkage, said heterocyclic ring has at least six ring members;

X is O, S(O)_m, NR₁₄ or CR₁₅R₁₆;

Y is O or S(O)_m or NR₁₇;

R₈-R₁₇ are one of said R₄ members;

m is 0-2 and

n is 0-5.

26. Process according to Claim 25 wherein said compounds according to Formula I are those as defined for Formula II

wherein

R₁, R₂ and R₃ are as defined for Formula I;

R₅ is independently one of said R₃ members and R₆ and R₇ are independently one of said R₄ members or are combined to form a heterocyclic ring having up to 9 members and containing O, N and/or S atoms, which ring may be substituted with alkyl, haloalkyl, alkoxy, alkenyl or alkynyl radicals each having up to 4 carbon atoms; provided that when said two R₆ and R₇ members are combined through a -hetero atom linkage, said heterocyclic ring has at least six ring members;

27. Process according to Claim 25 wherein said compounds according to- Formula I are those as defined for Formula III

wherein

R₁ and R₂ are C_1-5 alkyl;

R₃ and R₅ are hydrogen, bromo, chloro or fluoro;

R₆ is an R₅ member or nitro;

R₇ is an R₄ member or

R₆ and R₇ are combined through an -OCH₂(C=O) N-(R₄) -linkage to form a fused six-membered ring.

28. Process according to Claim 27 wherein

R₁ and R₂ are methyl;

R₃ is hydrogen, bromo or chloro;

R₅ is chloro or fluoro;

R₆ is chloro, fluoro or nitro and R₇ is a YR₁₁ member as defined in

Formula I

29. Process for the preparation of compounds according to Formula I wherein R₃ is a halogen, which comprises reacting a Formula I compound wherein R₃ is hydrogen with a halogenating agent.

30. Process according to Claim 29 wherein said Formula I compounds prepared by the halogenation process are those as defined for Formula III wherein R₃ is halogen.

31. Process according to Claim 30 wherein R₁ and R₂ are methyl, R₅ is chloro or fluoro and R₆ is chloro, fluoro or nitro.

32. Process for the preparation of compounds according to Formula I wherein one of said R₄ members is -YR₁₁ and R₁₁ is not hydrogen, which comprises reacting the corresponding compound of Formula I wherein R₁₁ is hydrogen with an acylating or alkylating agent.

33. Process according to Claim 32 wherein said compound of Formula I prior to said acylation or alkylation is a compound as defined for Formula III wherein R₇ is -YH.