IE912785A1 - Herbicidal substituted aryl alkylsulfonyl pyrazoles - Google Patents

Herbicidal substituted aryl alkylsulfonyl pyrazoles

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Publication number
IE912785A1
IE912785A1 IE278591A IE278591A IE912785A1 IE 912785 A1 IE912785 A1 IE 912785A1 IE 278591 A IE278591 A IE 278591A IE 278591 A IE278591 A IE 278591A IE 912785 A1 IE912785 A1 IE 912785A1
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chloro
members
methyl
methylsulfonyl
fluoro
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IE278591A
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Monsanto Co
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/84—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/18—One oxygen or sulfur atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The invention herein relates to certain substituted-arylpyrazole compounds, herbicidal compositions containing same, herbicidal methods of use and processes for preparing said compounds.

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-arylpyrazoletype 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 hetero20 cyclic, e.g., thienyl or aIky1-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 narrowleaf 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. -2- 41-21(3046)A SUMMARY OF THE INVENTION This invention relates to herbicidally-active compounds, compositions containing these compounds, processes for making them and herbicidal methods of wherein R, is hydrogen, C,.5 alkyl optionally substituted with an R4 member; Cj.e cycloalkyi or cycloalkenyl optionally substituted with C,.4 alkyl; R2 is 0,.5 alkyl optionally substituted with an R4 member; Rj is hydrogen or halogen and R4 is hydrogen, C,_8 alkyl, haloalkyl, alkylthio, alkoxyalkyl or poly alkoxy alkyl, C3.8 cycloalkyi, cycloalkenyl, cycloalky alkyl or cycloalkenylalkyl; C2.e alkenyl or alkynyl; carbamyl, halogen, amino, nitro, cyano, hydroxy, C4.,0 heterocycle containing 1-4 0, S(O)e and/or N hetero atoms, C6.12 aryl, aralkyl or alkaryl, —CXYRj, —CXR^, — CH2OCOR,0, — YR,,, —NR,jR,3, or any two R4 members may be combined through a saturated and/or X 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 or Rg.,5 members substituted with any of said R4 members; provided that when said two R4 members are combined through a -hetero O atom -C-N- linkage, said heterocyclic ring has at least six ring members; X is O, S(0)„ NRm or CR„RU; Y is 0 or S(0)a or NR,7; R8-R,7 are one of said R4 members; -3- 41-21(3046)A is 0-2 and n is 0-5.
A preferred subgenus of substituted-arylpyrazolyl compounds in this invention are those according to Formula II Rs wherein Rv R2 and Rj are as defined for Formula I; Rj 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 Ο, 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 ?« -C-N- linkage, said heterocyclic ring has at least six ring members.
Particularly preferred compounds of this invention are those according to Formula III fluoro; wherein R1 and Rj are CV5 alkyl; Rj and Rj are hydrogen, bromo, chloro or -4- 41-21(3046)A Rj is an Rj 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 R, and R2 are methyl; Rj is hydrogen, bromo or chloro; Rj is chloro or fluoro; Rj is chloro, fluoro or nitro; R7 is a YRn 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)l-methyl-5-(methylsulfonyl)-lH-pyrazole 4-Bromo-3-(2-fluoro-4-chloro-5—(2-propynyloxy)phenyl) 20 i-methyl-5-(methylsulfonyl) -lH-pyrazole 4-Chloro-3-(2-fluoro-4-chloro-5-(2-methoxyethoxy)phenyl) -l-methyl-5-(methy lsulf onyl) -IH-pyrazole 4-Bromo-3-(2-fluoro-4-chloro-5-(2-methoxyethoxy)phenyl) -l-methyl-5- (methylsulf onyl) -lH-pyrazole 6-(4-Chloro-l-methyl-5-(methylsulfonyl)-lH-pyrazol-3yl)-7-fluoro-4-(2-propynyl)-2H-l,4-benzoxazin-3(4H)-one (5-(4-Bromo-l-methy1-5-(methylsulfonyl)-lH-pyrazol-3yl)-2-chloro-4-fluorophenoxy)acetic acid, 130 methylethyl ester (5-(4-Chloro-l-methyl-5-(methylsulfonyl)-lH-pyrazol-3yl)-2-chloro-4-fluorophenoxy)acetic acid, 1methylethyl ester 2-(5-(4-Bromo-l-methyl-5-(methylsulfonyl)-lH-pyrazol-335 yl)-2-chloro-4-fluorophenoxy)propanoic acid, ethyl ester and -5- 41-21(3046,λ 2-(5- (4-Chloro-l-methyl-5-(methylsulf onyl, -lH-pyrazol3-yl) -2-chloro-4-fluorophenoxy)propanoic acid, ethyl ester.
Another aspect of this invention relates to 5 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 10 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 lower 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 l to 4 carbon atoms, especially the halomethyl radicals, e.g., trifluoroIE 912785 -β- 41-21(3046)λ 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., me thoxyme thoxy, methoxy ethoxy, ethoxymethoxy, ethoxyethoxy, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, propoxymethyl, isopropoxymethyl, butoxymethyl, isobutoxymethyl, tertbutoxymethyl, pentoxymethyl, hexoxymethyl, etc., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyc1opropyImethyl, cyclobuty Ime thyl, cyclopenty lmethyl, 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,l-dichloromethyl, 1,1-di30 bromomethyl, 1,1-dichloropropyl, 1,2-dibromopropyl, 2,3-dibromopropyl, l-chloro-2-bromoethyl, 2-chloro-3bromopropyl, trifluoromethyl, trichloromethyl, etc.
Representative heterocyclic members include: alkylthiodiazolyl; piperidyl; piperidylalkyl; dioxo35 lanylalkyl, thiazolyl; alkylthiazolyl; benzothiazolyl; halobenzothiazolyl; furyl; alkyl-substituted furyl; furylalkyl; pyridyl; alkylpyridyl; alkyloxazolyl; tetrahydrofurylalkyl; 3-cyanothienyl; thienylalkyl; -7- 41-21(3046)A 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, C3.7 spirocycloalkyloxazolidinyl, alkylaminoalkenyl; alkyl10 ideneimino; pyrrolidinyl; piperidonyl; perhydroazepinyl; perhydroazocinyl; pyrazolyl; dihydropyrazolyl; piperazinyl; perhydro-l,4-diazepinyl; quinolinyl, isoquinolinyl; 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 lower levels, particularly with some very noxious, herbicide-resistant plants. -β- 41-21(3046)A 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 per10 spective, 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 substi20 tuents, e.g., R.,-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 below in which R3 is H are prepared by this process step.
A 1) dithioketal 2) cyclization B 41-21(3046)A 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 anhy5 drous 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 -100’C to 100’C, preferably -78’C to 50’C. 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 tempera20 ture, etc. After completion of the reaction the intermediate 1-(substituted)-3,3-bis(alkylthio)-2propen-l-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 hydrazines with a Iky Ihydr a zines being preferred. Reaction temperature is in the range of -78’C to 150’C, preferably 10’C to 100’C. 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. -10- 41-21(3046)λ In the case of the addition of hydrazine to the intermediate 1-(substituted)-3,3-bis (alkylthio)-2propen-l-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 -78*C to 150’C, preferably 10*C to 100*C. 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-4fluoroanisole, which can be obtained from 2-chloro-4fluoro-phenol by methods known in the art (C. A. Buehler and D. E. Pearson, Survey of Organic Synthesis, pp. 285382, Wiley-Interscience, New York, 1970). Treatment of 2-chloro-4-fluoroanisole with titanium tetrachloride and dichloromethylmethylether at room temperature gives 2f luoro-4-chloro-5-methoxybenzaldehyde. The 2-fluoro30 4-chloro-5-methoxybenzaldehyde is converted to 2-fluoro4-chloro-5-methoxyacetophenone by treatment with methyl Grignard followed by oxidation using standard methods known in the art.
The above mentioned 2-fluoro-4-chloro-535 methoxyacetophenone and its analogous precursor, 2fluoro-4-chloro-5-methoxybenzaldehyde and processes for preparing them are the discovery of other inventors -11- 41-21(3046)A (Bruce C. Hamper and Kindrick L. Leschinsky) employed by the assignee herein. Table 1 shows typical examples of compounds prepared by Process I. 5 TABLE -1 PHYSICAL DATA FOR 3-ARYL-5-METHYLTHIOPYRAZOLES Λ Hi /—( R«· HX 10 αΛN 'R' Compound Rs Rd R? physical data No. mp (°C) or nD(25eC) 15 1 ch3 F H F light yellow oil 2 ch3 F a ch3 90.0 3 ch3 F a h 44.0-45.0 4 ch3 F a 0CH3 50.0-51.0 20 5 ch3 H H cf3 nD 1.5533 (25°Q 6 ch3 F och3 h nD 1.6036 (25°C) 7 ch3 α a h 90.0 25 8 H F H F 88.0 9 H F a och3 133-135 10 CH(CH3>2 F a och3 66-67 11 Et F a och3 nD 1.5989 (25°C) 30 12 ch3 F F H nD 1.5820 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 35 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 -12- 41-21(3Ο46)λ prepare novel compounds typified by those shown in Table II.
TABLE II PHYSICAL DATA FOR 3-ARYL-4-HALO-5-METHYLTHIOPYRAZOLES 5 Compound No. Ri Rs R« R? physical dam mp(°C)ornD(25eC) 14 ch3 F H f nD 1.5791 15 ch3 F nh2 F 123.0-124.0 16 ch3 F nh2 och3 nD 1.6212 17 ch3 F a F nD 1.5937 18 ch3 F a och3 87.0-88.0 19 ch3 F a ch3 83.0 20 ch3 F och3 H nD 1.5943 21 H F a och3 151.0-152.5 -13- 41-21(3046)A PROCESS 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,Sdioxide 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,Sdioxide 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 -78*C to 150*C, preferably 10’C to 100*C. 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 -1441-21(3046)A as crystallization or solvent extraction. If necessary, the product is purified by standard methods.
PROCESS III In this process description, one class of 5 products according to Formula D wherein R3 is halogen is prepared by the halogenation of the corresponding Formula C compound wherein Rj is hydrogen and p is 0 or 2. «3 SiOJpRa *1 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 -100’C to 150’C, preferably 10’C to 100’C. 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. -1541-21(3046,A 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 -100’C to 150°C, preferably -10 *C to 100’C. The reaction period may be chosen from the range of a few minutes to several days depending on the amounts of reagents, reaction temper25 ature, 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. 16- 41-21(3046)A F G 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 trial15 kylamine 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 -100’C to 150’C, ‘preferably -10’C to 100’C. 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).
J -17- 41-21(3046)A 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 R* 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 O’C to 150’C, preferably 10’C to 100’C. 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 concen30 tration 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 following step in the process. In this reaction any suitable solvent may be employed, although, anhydrous -1»- 41-21(3046)* solvents such as anhydrous acetonitrile are preferred, λ solution or slurry of the product of step A is treated vith copper salts including cupric halides, cuprous halides, mixtures of cupric and cuprous halides or other copper salts and their mixtures and vith an alkyl nitrite or other organic nitrites, such as t-butylnitrite. Reaction temperature is in the range of O’C to 150’C, preferably 10’C to 100’C. 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 YRn and Rn is not hydrogen.
The reaction can be carried out as a solution or suspension in any suitable solvent or neat. A Lewis acid such as, but not limited to, 8Br3, A1C1S, 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 O’C to 150’C, preferably 10’C to 100’C. 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 -19- 41-21(3046)λ 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 YRn and Rn 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 O’C to 150’C. preferably 10’C to 100’C.
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 YCH2.n(R1a)nCOYR20) from the corresponding compounds of Formula K. The radicals R18.2o are as previously defined for the said R* 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 O’C to 150’C, preferably ’C to 100’C. 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 -21- 41-21(3046)A 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 reac30 tion temperature is in the range of -20*C 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 halogen35 ating 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. -22- 41-21(3046)* 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 dimethy15 formamide or the like may be added for the purpose of promoting this reaction. The reaction temperature is in the range of -20*C 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.
EBOCESS-X This process describes the preparation of compounds of Formulae Ο, P, Q, R, S or T (Formula II compounds in which the R7 substituent is alkyl, substituted alkyl, haloalkyl, carboxaIdehyde, carboxylic acid or a carboxylic acid derivative such as the previously defined CXYRj or CXR^) from compounds of Formula N. The radicals R21 and R22 are as previously defined for the R4 members and X, and X2 are halogens. Process schematics are shown below. 41-21(3046)λ T s -24- 41-21(3046)A In the first step of this process, compounds of Formulae N are converted to either compounds of Formula 0 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 -100*C to 150*C, preferably 10*C to 100*C. 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 0’C to 150’C, preferably 10’C to 100’C. The reaction period -25- 41-21(3046)λ 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 concen5 tration 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 O’C to the boiling point of the inert solvent, preferably 10’C to 100’C. 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 reac20 tion 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 O’C to the boiling point of the inert solvent, preferably 10’C to 100’C. 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 crysIE 912785 -26- 41-21(3046)A 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 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, 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 -20'C 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 reac35 tion product by evaporation or distillation. The resultant acid halide may be subjected to an amine or alcohol directly and purified by the usual means. -27- 41-21(3046)λ 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 -20’C 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 followed 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, alkylnitrlies, 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 25’C to the boiling point of the solvent employed.
The reaction period may be chosen from the range of a 41—21(3046) 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 pro5 duct(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 agueous 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 O’C to 150’C, preferably 10’C to 100’C.
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. XU In this process step, compounds of Formula V (Formula I compounds in which R2 is CHjRq where R^ is one of the previously defined R4 members) are prepared from compounds of Formula I where R2 is methyl. v -29- 41-21(3046)A Any suitable solvent nay 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 -100’C to the boiling point of the solvent employed with -78’C to 25’C being preferred. Initially, the compound of Formula I is treated with a strong base such as an alkyl metal, metal hydride, metal amide, etc., followed 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 l.
Y -30- 41-21(3046)λ 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 O’C to 150*C, preferably 10’C to 100’C. 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 V? 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, plati30 num 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. -3141-21(3046)A 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 15* and 5.4 mL (0.09 mole) CS2 were added over 15 min. keeping the temperature at 15*C 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 20*C. 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-(2,5difluorophenyl)-3,3-bis(methylthio)-2-propen-l-one as a yellow solid, mp 105.5*C; 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 Ο,,Η^Ο^: C,50.75; H,3.87; S,24.63.
Found: C,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 24*C. The solution was refluxed for 6 hr. The solution was stripped in vacuo. The residue was purified chromatoIE 912785 -32- 41-21(3046)* 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)-ΙΗ-pyrazole as a light yellow oil; Anal. Calc, for C^H^F^sJ: 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)-l-methyl-5methylthio-lH-pyrazole and 5-(2,5-difluorophenyl)-1methy1-3-methylthio-lH-pyrazole.
A. To a solution of 5.2 g l-(2,5-difluorophenyl)-3,315 bis(methylthio)-2-propen-l-one in 50 mL acetonitrile at 24*C was added 1.3 mL of anhydrous hydrazine over a period of 3 minutes. The reaction was heated to 95’C for 1 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) -ΙΗ-pyrazole as a white solid, mp 88’C.
Anal. Calc, for C10H8F2N2S,: 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 K2COj, and 1.0 mL methyl iodide in 75 mL acetone was stirred overnight at 25’C. 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)-l-methyl-5methylthio-lH-pyrazole (analysis given in Example 1) and 0.35 g (10%) of 5-(2,5-difuloropheny1)-1-methy1-3IE 912785 -33- 41-21(3046)* (methylthio)-ΙΗ-pyrazole as a light yellow oil, n£5 1.5731.
Anal. Calc, for C^H^F^S,: C,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)-l-methyl-5-(methylthio)-1Hpyrazole.
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 40 *C and was stirred at that temperature for 30 minutes. The solution was then cooled to O’C 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 l’C. After the addition was complete, the reaction was stirred for 15 minutes at O’C, followed by the addition of methyl iodide (23.6g, 0.38 mol) never letting the solution temperature rise above l’C. The solution was stirred using no cooling until it reached 10’C, at which time the reaction solution was poured onto IL of ice water. Two crops of a filterable yellow solid were collected to give a total yield of 48.lg (96% yield) of the dithioketal. The dithioketal (47g, 0.180 mol) was dissolved in acetonitrile (500 ml) and methyl hydrazine (2lg, 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-(2,435 di fluorophenyl)-l-methyl-5-(methylthio) -ΙΗ-pyrazole as an amber oil. ’HNMR (CDC13) ppm: 7.82 (q, J=6.6, IH) , 6.78 (m, 2H), 6.55 (d, J=3.6, IH), 3.83 (S, 3H), 2.34 (S, 3H). -34- 41-21(3046)A Anal. Calc, for C11HWF2N2S1: 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 working embodiments of Process II.
Example 4 This example describes the preparation of 3(2,5-difluoropheny1) -1-methy1-5-(methylsulfony1)-1Hpyrazole.
A solution of 2.66 g (0.011 mole) of the product of step (B) , Example l, in 50 mL methylene chloride was cooled to -5*C. A solution of 7.6 g (0.022 mole) 50-60% inch 1 or o-perben zoic 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)-l-methyl-5-(methyl20 sulfonyl)-ΙΗ-pyrazole as a white solid, mp 126-127’C; Anal. Calc, for C11H10F2O2S1: C,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)ΙΗ-pyrazole.
To a solution of 1.12 g of 5-(4-chloro-230 fluoro-5-methoxyphenyl)-3-(methylthio)-ΙΗ-pyrazole in a mixture of 30 mL of glacial acetic acid and 15 mL of ethanol was added 3.2 g of Oxone·. The heterogeneous mixture was heated to 85*C and after 2 hours was poured into ice water. The resultant mixture was extracted three times with methylene chloride and the organic extracts concentrated to afford an oily residue.
Solution of the oily residue in 10% aqueous NaOH followed by neutralization with concentrated HCI -35- 41-21(3046)A afforded a solid precipitate which was collected and washed with water to afford 0.60 g (48%) of 5-(4chloro-2-fluoro-5-methoxyphenyl) -3-(methylsulfonyl) -1Hpyrazole. An analytical sample was obtained by recrystallization from methanol/water to give a yellow, crystalline solid; mp 213-216 (dec.).
Anal. Calc, for C11H10N2O3F1: C,43.36; H,3.31; N,9.19; S, 10.52.
Found: C,43.51; H,3.33; N,9.10; S,10.44.
Example 6 This example describes the preparation of 4chloro-3-( 2-f luoro-4-methoxyphenyl) - 1-methyl-5- (methylsulfonyl) -ΙΗ-pyrazole.
To a O’C solution of 4-chloro-3-(2-fluoro-4methoxyphenyl) -l-methyl-5-(methylthio) -lH-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 twice 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’C.
Anal. Calc, for C^^F^O^Cl,: C,45.22; H,3.79; N,8.79.
Found: C,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 4chloro-3-(2,5-dif luorophenyl) -l-methyl-5-(methylsul35 fonyl)-lH-pyrazole.
At 25’C, 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 -36- 41-21(3046)* period of 50 minutes. The reaction vas alloved to stir for 45 minutes. The reaction solution vas poured into 300 mL ice water, and extracted with diethyl ether. The ether vas washed with a saturated sodium bicarbonate solution, dried over anhydrous MgSO4, and concentrated in vacuo. The residue vas purified chromatographically using 30% ethyl acetate in hexane as the eluent to give 1.35 g (84%) of 4-chloro-3-(2,5-difluorophenyl)l-methyl5-(methylsulfonyl)1H—pyrazole as a white solid, mp 77*C; Anal. Calc, for Ο,,ΗφϋΙ,Γ^Ο^: C,43.08; H,2.96; N,9.13; S,10.45; Cl,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 4chloro-3-(2-f luoro-4-methoxyphenyl) -l-methyl-5- (methylthio) -lH-pyrazole.
To a 0’C solution of 3-(2-fluoro-4-methoxyphenyl) -l-methyl-5- (methylthio) -ΙΗ-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 vith brine, dried over anhydrous magnesium sulfate and stripped In vacuo to give a yellow oil, — 1.5943 at 25*C.
Anal. Calc, for C^jF^O^Cl,: C,50.26; H,4.22; N,9.77 Found: C,49.84; H,4.13; N,9.61.
Examples 9 and 10 describe specific working embodiments of Process IV.
Example 9 This example describes the preparation of 4chloro-3- (2,5-dif luoro-4-nitrophenyl) -l-methyl-535 (methylsulfonyl)-lH-pyrazole. -37- 41-21(30«)* At 24*C, 1.5 g (4.9 mmole) 4-chloro-3-(2,5difluorophenyl)-l-methyl-5-(methylsulfonyl)-lH-pyrazole, vas slovly added to 25 mL of fuming nitric acid. The reaction vas stirred at'30'C for 30 minutes. The reaction vas poured into 300 mL of ice. The slurry vas filtered and the cake washed well with water and air dried. The solid was recrystallized from methyIcyclohexane to give 1.13 g (66%) of 4-chloro-3-(2,5-difluoro4-nitrophenyl)-l-methyl-5-(methylsulfonyl)-lH-pyrazole as a beige solid, mp 147'C; Anal. Calc, for : C,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 4chloro-3-(4-chloro-2-fluoro-5-nitrophenyl) -l-methy 1-5(methylsulfonyl)-lH-pyrazole.
To a solution of 3g (0.0093 mol) of 4-chloro20 3-(4-chloro-2-fluorophenyl)-l-methyl-5-(methylsulfonyl)ΙΗ-pyr azole in 3 mL of concentrated sulfuric acid vas added a mixture of 1 mL of concentrated nitric acid in 3 mL concentrated sulfuric acid, dropwise. This mixture vas then stirred at 25’C for 2 hours. The reaction mixture was then poured into ice-water and extracted vith ether. The organic extracts were then washed three times vith 100 mL of aqueous NaCl, dried (MgSOJ , filtered and concentrated to afford 2.3g (67%) of 4chloro-3- (4-chloro-2-f luoro-5-nitrophenyl) -l-methy 1-530 (methylsulfonyl)-lH-pyrazole as a yellow solid.
Chromatography (10% EtOAc/CH2Cl2) afforded an analytical sample, mp 111-115*C.
Anal. Calc, for C^HgNjO^Cl^S, + 1/4 EtOAc: C,36.45; H,2.60; N,10.85.
Found: C,36.39; H,2.26; N,10.91.
Examples 11 and 12 describe specific working embodiments of Process V. -38- 41-21(3046)λ Example ll This example describes the preparation of 4chloro-3-(2-f luoro-5-methoxy-4-nitrophenyl) -l-methyl-5(methylsulfonyl)-lH-pyrazole.
A mixture of 4.8 g (0.0137 mole) of the product of Example 9, 1.9 g (0.014 mole) K2COj, and 5 mL methanol vas slurried in 50 mL DMSO at 25’C. The reaction vas stirred at 45’C for 8 hours. The reaction vas cooled, diluted with 100 mL cold water, and extracted four times with ethyl acetate. The ethyl acetate extracts were washed with brine, dried over anhydrous MgSO4, and stripped in vacuo. The residue vas recrystallized from ethyl acetate/hexane to give 4.21 g (84%) of 4-chloro-3-(2-fluoro-5-methoxy-4-nitrophenyl)15 l-methyl-5-(methylsulfonyl)-lH-pyrazole as a yellow solid, mp 178.5-180’C; Anal. Calc, for C^jCI^NjOjS,: 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-l-methyl-5-(methy lsulf onyl)-lH-pyrazol-3-yl)4-fluoro-N-(1-methylethyl)-2-nitrobenzenamine.
To a solution of 4-chloro-3-(2,5-difluoro-4nitrophenyl) -l-methyl-5- (methylsulf onyl) -lH-pyrazole (7.6g, 0.0218 mol) in n-methyl pyrrolidinone (50 ml) vas 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 60’C for two hours and determined complete by TLC. The reaction vas 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-l-methy 1-5-(methylsulfonyl) -lH-pyrazol-3-yl] -4-f luoro-N- (1-methylethyl) 2-nitrobenzenamine as an orange solid after recrystalization from ethanol/methyl cyclohexane, mp 152*C. -39- 41-21(3046)A Anal. Calc, for 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 45 chloro-3-(4-chloro-2-f luoro-5-methoxyphenyl) -l-methyl5-(methylsulfonyl)-ΙΗ-pyrazole is a specific embodiment of Process VI.
(A.) A slurry of 3.3 g (9.1 mmole) of 4-chloro-3-(2f luoro-5-methoxy-4-nitrophenyl) -l-methyl-5- (methyl10 sulfonyl)-ΙΗ-pyrazole in 100 mL of acetic acid vas heated to 80*C under nitrogen and treated portionwise with 1.5 g (27 mmole) of iron powder. After 20 minutes at 85 *C, the mixture vas allowed to cool and filtered through Celite·. 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 ag. NaHCOj, water, 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 25*C vas 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 vas added to the reaction mixture over 5 minutes. After 1 hour at 28‘C the reaction mixture vas concentrated in vacuo. The reaction residue vas 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 vas purified chromatographical ly using 50% ethyl acetate in hexane as the eluent to give 2.64 g (83%) of 4-chloro-3-(4-chloro2-fluoro-5-methoxyphenyl) -l-methyl-5- (me thy lsulfonyl) ΙΗ-pyrazole as a white solid, mp 127.5’C.
Anal. Calc, for C12H11C12F1N2O3S1: 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. -40- 41-21(3046)A Example IA This example describes the preparation of 2chloro-5-[4-chloro-l-methyl-5-(methylsulfonyl)-lHpyrazol-3-yl]-4-fluoro-,N-2-propenylbenzenamine.
A solution of 1 g (0.0023 mol) of N-[2-chloro5-[4-chloro-l-methyl-5-(methylsulfonyl)-lH-pyrazol-3yl]-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 vas allowed to stir at 70*C for 24 hours. This solution vas diluted with EtOAc, washed with three times 100 mL of 5% HCI, dried (MgSO4), filtered and concentrated to afford 0.9g of a red oil. This oil vas dissolved in 20 mL of methanol and 3 mL of 10% NaOH vas added. This mixture vas stirred at 25’C for 8 hours. The reaction mixture vas diluted with EtOAc, washed with three times 100 mL of aqueous NaCl, dried (MgS04), filtered and concentrated to afford 0.8g of a red oil. Chromatography (CH2C12) afforded 0.6g (69%) of 2-chloro-5-[4-chloro-l-methyl-520 (methylsulfonyl)-lH-pyrazol-3-yl]-4-fluoro-N-2-propenylbenzenamine as a yellow oil, n£* · 1.5956.
Anal. Calc, for CUHUN3O2C12F,S1: C,44.46; H,3.73; Ν,ΙΙ.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-l-methyl-5- (methylsulfony1) -1Hpyrazol-3-yl] -4-f luorophenyl ] -methanesulf onamide.
To a solution of 0.5g (0.001 mol) of N-[2chloro-5-(4-chloro-l-methyl-5-(methylsulfonyl)-1H30 pyrazol-3-yl]-4-f luorophenyl ]-N-(methylsulf onyl) methanesulf onamide in 20 mL of methanol vas added 2 mL of 10% NaOH. This mixture vas stirred at 25C for 4 hours. The reaction mixture vas diluted with EtOAc, washed with three times 100 mL of 5% HCI, dried (MgSO4), filtered and concentrated to afford 0.2g (48%) of N-[2chloro-5-[4-chloro-l-methyl-5-(methylsulfonyl)-1Hpyrazol-3-yl]-4-fluorophenyl]methanesulfonamide as a -41- 41-21(304«)λ yellow-tan solid. Chromatography (EtOAc) afforded an analytical sample, mp 165-166C.
Anal. Calc, for C^^NjO^CljF^ + 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 4chloro-3-(4-chloro-2-fluoro-5-hydroxypheny1)-1-methy15-(methylsulfonyl) -lH-pyrazole.
A solution of 1.15 g (3.25 mmole) 4-chloro-3(4-chloro-2-f luoro-5-methoxyphenyl) -l-methyl-5- (methylsulfonyl)-lH-pyrazole in 30 mL methylene chloride was chilled to O’C and treated with 4 mL of a IM methylene chloride solution of BBr3 (4.0 mmole) was added slowly over 5 minutes. The solution was allowed 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-(420 chloro-2-f luoro-5-hydroxyphenyl) -l-methyl-5- (methylsulfonyl)-lH-pyrazole as a beige solid, mp 190.5*C; Anal. Calc, for C^H^C^F^OjS,: C,38.95; H,2.67, N,8.26.
Found: C,38.93; H,2.67; N,8.43. Examples 17, 18, 19 and 20 describe specific working embodiments of Process VIII.
Example 17 This example describes the preparation of 2chloro-5-[4-chloro-l-methyl-5-(methylsulfonyl)-lHpyrazol-3-yl]-4-f luoro-N-(1-methylethyl) -benzeneamine.
A solution of 0.5g (0.0015 mol) of 2-chloro5-[4-chloro-l-methy1-5-(methylsulfonyl)-lH-pyrazol-3yl]-4-fluorobenzenamine and 2 mL of 2-iodopropane in 5 mL of anhydrous DMF was stirred at 75*C for 6 hours, then at 25’C for 2-1/2 days. The reaction mixture was diluted with EtOAc, washed with two times 50 mL of 5% HCI, dried (MgSOJ , filtered and concentrated to afford 0.5g red oil. Chromatography (methylene chloride) afforded 0.25g (44%) of 2-chloro-5-[4-chloro-l-methyl -42- 41-21(3046)* - (methy lsulf onyl) -lH-pyrazol-3-yl]-4-fluoro-N- (1methylethyl)-benzeneamine as a red solid, mp 118’C121‘C.
Anal. Calc, for CUH15N3O2C12F1S1 -«-1/2 H2O: C,43.20; H,4.40; N,10.79.
Found: C,42.88? H,4.02? N,10.70.
Example 18 This example describes the preparation of N(2-chloro-5- [ 4-chloro-l-methyl-5- (methylsulf onyl) -1H10 pyrazol-3-yl]-4-fluorophenyl]-alanine, ethyl ester.
A solution of alanine, N-[2-chloro-5-[4chloro-2-methyl-5-(methylsulfonyl)-lH-pyrazol-3-yl]-4fluorophenyl]- in ethanol with a catalytic amount of acetyl chloride was allowed to stir at 25’C for 18 hours. This solution was diluted with EtOAc, washed with water, two times with 100 mL of aqueous potassium carbonate, dried (MgSOJ , filtered and concentrated to afford 0.5g of a yellow oil. Chromatography (CH2C12) afforded 0.17g (20%) of N-[2-chloro-5-[4-chloro-l20 methyl-5-(methylsulfonyl)-lH-pyrazol-3-yl]-4-f luorophenyl] -alanine, ethyl ester as a yellow oil. 1HNMR (400 MHz, CDClj) 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, CDClj d 25 128 (s, IF) ppm.
Anal. Calc, for CuHieN3O4Cl2F,S1: C,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 N30 [2-chloro-5-[4-chloro-l-methyl-5-(methylsulfonyl) -1Hpyr a zol-3-yl]-4-f luor opheny 1 ] -N- (methy lsulfonyl) methanesulfonamide.
To a solution of 0.5g (0.0015 mol) of 2chloro-5- [4-chloro-l-methyl-5- (methylsulfonyl) -1H35 pyrazol-3-yl]-4-fluorobenzeneamine in 20 mL of methylene chloride was added 0.33g (0.0033 mol) of triethylamine followed by 0.37g (0.0033 mol) of methanesulfonyl chloride. This mixture was stirred at 25’C for 18 -43- 41-31(3046)A hours. The reaction mixture vas diluted with EtOAc, washed with three times 100 mL of 5% HCl, dried (MgSO4), filtered and concentrated to afford 0.7g (94%) of N-[2chloro-5-[4-chloro-l-methyl-5-(methylsulfonyl) -1H5 pyrazol-3-yl]-4-fluorophenyl] -N-(methylsulfonyl) methanesulfonamide as an off-white solid. Chromatography (EtOAc) afforded an analytical sample, mp 234237*C.
Anal. Calc, for C^H^jO^Cl^Sj + 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) 15 phenyl) -l-methyl-5-(methy lsulf onyl) -lH-pyrazole A mixture of 0.87 g (2.5 mmole) of 4-chloro3-(4-chloro-2-fluoro-5-hydroxyphenyl) -l-methyl-5(methy lsulf onyl)-lH-pyrazole, 0.4 g (3.0 mmole) K2CO3, and 0.3 mL (3.0 mmole) propargyl bromide were slurried in 10 mL DMSO at 25*C. The reaction vas stirred at 45*C for 16 hours. The reaction was cooled, diluted with 100 mL cold water, and extracted four times with ethyl acetate. The ethyl acetate extracts were washed with brine, dried over anhydrous MgSO4, and stripped in vacuo.
The residue vas 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-(2propynyloxy)phenyl) -l-methyl-5-(methylsulf onyl) -1Hpyrazole as a tan solid, mp 135*C. Anal. Calc, for CUH11C12F1N2OJS1: C,44.58; H,2.94, N,7.43.
Found: C,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-l-methyl-5- (methylsulf onyl) -1Hpyrazol-3-yl) -4-fluorophenoxy) -propanoic acid. -44- 41-21(3046)* To a slurry of 3.77 g (8.6 mmole) 2-(2-chloro5-(4-chloro-1-methy1-5-(methylsulfonyl)-lH-pyrazol-3yl)-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 vith 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-l-methyl-5(methylsulfonyl)-lH-pyrazol-3-yl)-4-fluorophenoxy)propanoic acid as a white solid, mp 56*C.
Anal. Calc, for CUH13C^2F1N2°5S1: C,40.80; H,3.19; N,6.81.
Found: C,40.87; H,3.24; N,6.69.
Example 22 This example describes the preparation of 220 (2-chloro-5-(4-chloro-l-methyl-5-(methylsulfonyl)l-pyrazol-3-yl)-4-fluorophenoxy)-N-methylpropanamide.
To a solution of l.l7g (5.9 mmole) 2-(2chloro-5-(4-chloro-l-methyl-5-(methylsulfonyl)-1Hpyrazol-3-yl)-4-fluorophenoxy)-propanoic acid in 10 mL methylene chloride vas added 0.8 uL (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 vas stripped to dryness in vacuo. The residue vas dissolved in 5 mL THF and at 0*C added to 10 mL of a 40% aqueous solution of methyl amine over 5 minutes. The reaction mixture was alloved 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-chloroIE 912785 -45- 41-21(3046)* l-methyl-5-(methylsulfonyl)-lH-pyrazol-3-yl)-4-fluorophenoxy ) -N-methylpropanamide as a white solid, mp 178’C; 1HNMR (CDClj) ppm: 1.55 (d, 3H) , 2.81 (d, 3H), 3.23 (s, 3H), 4.17 (s, 3H), 4.64 (q, 3H), 6.65 (br, IH), 6.97 (d, IH), 7.22 (d, IH).
Anal. Calc, for C15H16C12F1N3O4S1: 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 working embodiments of Process X.
Example 23 This example describes the preparation of (((2-chloro-5-(4-chloro-l-methyl-5-(methylsulfonyl)-1Hpyrazol-3-yl)-4-fluorophenyl)methyl)thio)acetic acid, ethyl ester.
At 25’C, 1.25g (3.0 mmole) 3-(5-(bromomethyl)4-chloro-2-fluorophenyl)-4-chloro-l-methyl-5-(methylsulfonyl) -lH-pyrazole, 0.5g (3.3 mmole) K2CO3, and 0.4 mL (3.3 mmole) ethyl bromoacetate were slurried in 15 mL acetone. The reaction was stirred at 20’C for 8 hours.
The reaction was poured into 150 mL water, filtered and air dired. The solid was recrystallized from methylcyclohexane to give 1.2g (93%) of (((2-chloro-5-(4chloro-l-methyl-5- (methylsulfonyl) -lH-pyrazol-3-yl) -4fluorophenyl)methyl)thio)acetic acid, ethyl ester as a white solid, mp 110’C.
Anal. Calc, for CUH17C12F,N2O4S2: C,42.20; H,3.76; N,6.15.
Found: C,42.25; H,3.72; N,6.18.
Example 24 This example describes the preparation of 230 chloro-5- (4-chloro-l-methyl-5- (methylsulfonyl) -1Hpyrazol-3-yl)-4-fluoro-N-methylbenzamide.
To a solution of l.34g (3.7 mmole) 2-chloro5- (4-chloro-l-methyl-5- (methylsulfonyl) -lH-pyrazol-3yl)-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 -46- 41-21(3046)A solution was stripped to dryness in vacuo. The residue was dissolved in 5 mL THF and at O’C 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-l-methyl-5(methylsulfonyl)-lH-pyrazol-3-yl)-4-fluoro-N-methyl10 benzamide as a white solid, mp 187’C.
Anal. Calc, for C13H12C12F1NjOjS1 : 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 215 chloro-5-(4-chloro-l-methyl-5-(methylsulfonyl)-1Hpyrazol-3-yl)-4-fluorobenzenethiol and is a specific working embodiment of Process XI.
A slurry of 9.3g (0.022 mole) 2-chloro-5-(4chloro-l-methyl-5-(methylsulfonyl)-lH-pyrazol-3-yl)-420 fluorobenzenesulfonyl chloride and 29g (0.44 mole) zinc powder in 125 mL glacial acetic acid was stirred at 90’C 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-l-methyl-5-(methylsulfonyl)-1Hpyrazol-3-yl)-4-fluorobenzenethiol as a white solid, mp lll’C.
Anal. Calc, for CnH9Cl2F,N2O2S2: 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 435 chloro-3-(4-chloro-2-fluoro-5-methoxyphenyl) -1-methyl5-(ethylsulfonyl)-lH-pyrazole and is a specific working embodiment of Process XII. -47- 41-21(3046)A All equipment was flame dried under nitrogen.
To a solution of 4-chloro-3-(4-chloro-2-fluoro-5methoxyphenyl)-l-methyl-5-(methylsulfonyl)-lH-pyrazole (l.25g, 3.5 mmol) in 50 ml dry tetrahydrofuran at -78*c was added a IM solution of n-butyl lithium (3.5 ml, 3.5 mmol) never letting the temperature rise above -60*C.
The reaction was stirred for 30 minutes at -78*c 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 65*c.
Anal. Calc, for C^H^NjOjS^^: C,42.52; H,3.57; N,7.63.
Found: C,42.53; H,3.80; N,7.71.
Example -27 This example describes the preparation of 720 (4-chloro-l-methyl-5-(methylsulfonyl)-lH-pyrazol-3-yl]6-fluoro-2H-l,4-benzothiazin-4(3H)-one and is a specific working embodiment of Process XIII.
A solution of ((5-(4-chloro-l-methy1-5(methylsulfonyl)-lH-pyrazol-3-yl)-4-fluoro-2-nitro25 phenyl)thio)acetic acid, ethyl ester (3.0g, 6.6 mmol) in glacial acetic acid (150 ml) was heated to 80*C and iron (1.5g, 0.0268 mol) was added all in one portion. The solution was heated between 80*C-100*C 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 245*C; 'hNMR (CDClj) 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 C,41.55; H,2.95; N,11.18.
Found: C,41.72; H,3.09; N,10.81. -4«- 41-21(3046)λ Tables 3 and 4 show examples of compounds prepared by Processes II-XIII and/or any combination of these processes as exemplified in Examples 1-27. -49- 41-21(3046)* Tabto). Pkyrical Dm for bMcthyl-3-Myl-S-meihylutlfQaylpyrazolei. ee Z CH2OCH2CH2OCH3 nD 1.3639 □ □COOOOODCOO asoooooooooo -5041-21(3046)A h <8 ί ο ο $ 5? ο ο ο ο Βα - ri w «η «μ ©©©οόόο^όοοόόόόΏ© θ ....... .
£ ® = ZS(!;55SR3?5*^S »Ί S s |Ι h δ δ δ U. = Ζ Ζ Ζ Ζ 4 οοσσσσοσοσοοοσοοσ σσσσσσσσσσσσσσσσσ -5141-21(3046)A 55?*-5S2 = o$o* oo 2 = 195222 = 2929«22 «δ δ 5 δ δ i i § i ‘ δ fc X -R SS X δ £ £ r γ ι- δ Η䧧§§ I I I Π ί § § § § § OC1I(CH3)C-CH 29.0-30.0 □ οσοοοοοοοοσσοοοο οοοσοοοοοοοοοοοοο «η <η ssssRasssssjsss 41-21(3046)A P © o © © ό © o © © s ri w «s <*» r* w ao <> an IM IM οοοοοοσοοσοσσοοοσ B.B.Iklka.e.tklkB.B.
B. Ik Ik σσοσσσσοσοοοσσσσσ (α»1) -5341-21(3046)A ii '8 •n _ fc fc — β — © © © ^ _. _ ό eS®aS9»»Ao> — S ® ®· ® » I S k152S = = 25P55 «i i ? 11 555¾¾¾¾ δεδδδδδ - . (Λ4Ο<Λ<Λ(Λ<Λ«Λ<Λ<Λ(ΛΧ tti S ξ σοοοσσσσοσσχχχ NII2 OCH(CHj)2 103.0 Η.Β.Β.Κ.Β.Β.Β.ΧΒ.Β.&Β.0.(1.ΧΧ& σσσσσσσσσσσσσσσσσ 2 5 5 S S 5 S 5 J S $ S ? & ! S I -5441-21(3046)A P ll o o Ci ©0000*00^ ©*>©*!© © r'xS'ex’ipiXf^wr'A*'··'! — rs i1 „ J? S S 8 £? » J? u- Q <λ I! π ι § | δ § s *η I «Iδ «η λ jS γ § s δ s § s § O.lLB.ibBiBka.a.BilklkB.B.B.II.B.U. σσσσσσσσσσσσσσσσσ SSSS8S8S ο — ί* 41-21(3046)A οόοόοοοο ο σ» β* · “ λ<μ<«222228ϊ = σσο£ξχ = οσσσοοσο II.ILtoilLlkU.ll.U.U.il.U.lliUillitLU.U.
QXXXX£2£££££££00C Table 3. (cwtt) SSsaSSSS&SRSSSRSS -5641-21(3046)A o σί «. £ £ 0 £ 0 et ee U.U.U.Ub(I.U.U.Ifa οσοοσοοο -57- 41-21(3046)* 123.0-124.0 yiica) Dan for 3-Aiyl-5-allcylwlfoayl Table 4. PhyacelDmfor>Aiyl*S*alkylMlfoayl ~59' <1-21(3046)* Dm· for 3-Aryl-3-alkyl*ulfoaylpyiuok*. -60- 41-21(30461* 4. Physical Dm· far 3-Aiyl-3-*IkylmlfonylpyTtioles.
X -61- 41-21(3046)A PRE-EMERGENCE 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. A 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: -62- 41-21(3046)A Yens- Yellow nutsedge Anbg - Annual bluegrass Sejg - Seedling johnsongrass Dobr - Downy Brone Bygr - Barnyardgrass Mogl - Morningglory Cobu - Cocklebur Vele - Velvetleaf Inmu - Indian mustard 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. -63- 41-21(3046)A TABLB 5 PREEMERGENCE TESTS % PLANT INHIBITION Y A s D BMC V 1 w • n • o y ο o • n i Cpd. Rat· n b j b 9 9b 1 b No. kg/ha 9 9 r t 1 u • 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 1 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 CCC 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 CCC 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 CCC c c c 38 11.21 80 80 80 50 C 90 70 90 c c 39 11.21 90 C 90 80 CCC 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 CCC c c c 43 1.12 70 C C 50 90 C C c c c -64- 41-21(3046)X TABL1 5 (continued! ESEQSSSEfiSE-XESZS PLANT IWIBI.TI9P Y • λ n • 0 o B Y M o c o V • I n H 1 !pd. Rat· n b 3 b 9 9 b 1 b io. kg/ha • 9 9 r r 1 u • 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 53 1.12 0 10 0 90 40 90 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 70 40 70 10 C 90 C C C c 59 11.21 SO 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 41-21{3046)Α TABLE S (continued} PREEMERGENCE TESTS % PLANT INHIBITION Y • A n S • 0 o B y M o C o V • z n W i Rat· n b j b 9 9 b 1 m b kg/ha 9 9 r r 1 u • u w 1.12 60 C 90 40 C C 70 c C C 1.12 0 C 70 80 c C 80 c c C 1.12 20 90 60 20 90 90 70 c c 90 1.12 60 C 90 50 90 C 30 c c C 1.12 30 C 90 40 C c 30 c c c 1.12 30 C 90 40 C 80 30 c c 90 1.12 60 20 60 20 80 C C 90 90 90 1.12 SO 10 60 30 50 90 80 80 90 80 1.12 40 0 80 10 20 90 60 80 90 80 1.12 70 20 70 0 80 C C C C C 1.12 50 0 70 20 80 C 40 C 90 C 1.12 60 20 30 20 70 c 90 90 90 80 1.12 20 0 20 20 80 c 70 C 80 80 1.12 60 C 90 50 C c C c C C 1.12 90 C 70 20 90 c c c c c 1.12 60 10 70 20 20 c 60 90 90 90 1.12 60 c C 90 C 90 80 c c c 1.12 50 50 80 20 90 C 90 c c 90 1.12 70 C C C C C 60 c c C 1.12 0 80 70 80 80 c 80 c c C 11.21 90 90 90 90 90 90 C c c C 1.12 0 20 30 20 20 40 20 40 80 90 -66- 41-21(3046)A TABLK 5 (continual PREEMgRCENCT TESTS % PLANT INHIBITION Y • A n' S • D o 8 y M o C o V • I n H i Cpd. Rat· n b j b 9 9 b 1 a b No. kg/ha a 9 9 r r 1 u • 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 SO 70 0 102 11.21 40 30 60 30 80 SO 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 SO 108 11.21 30 90 90 70 80 90 80 c c c 41-21<3046)λ TABU 5 /continued) PRBBMgRCBMCB TESTS PLAMT INHIBITIQM Y a A n s • D o B y M o c o V • I n w i Rat· n b J b 9 9 b 1 B b kg/ha a 9 9 r r 1 u • U w 11.21 70 C c 60 90 80 90 c C C 11.21 80 C 90 80 90 90 90 c c 80 11.21 40 C 70 70 C 20 C c c 70 11.21 80 c C 70 90 C 70 c c C 1.12 60 80 90 50 C 30 60 90 c 90 11.21 0 0 0 20 20 70 20 30 30 20 11.21 C 40 90 80 C C C c c C 11.21 90 0 80 20 60 90 60 c c C 11.21 70 80 90 70 C 70 90 c c c 11.21 0 0 0 0 0 0 0 80 20 10 11.21 0 0 0 0 0 0 0 30 20 10 11.21 0 0 0 0 0 0 0 0 30 20 11.21 0 0 0 0 0 0 0 20 0 0 11.21 0 0 0 0 0 0 0 10 10 20 11.21 40 90 90 20 90 70 40 80 90 90 11.21 50 20 40 20 70 70 20 90 c 50 11.21 0 0 0 0 0 20 0 70 40 40 11.21 30 60 40 20 80 70 20 C 90 80 11.21 80 c c C c c c c C C 1.12 80 c 90 70 90 90 c c c c 11.21 40 70 60 90 80 80 c c c c 1.12 40 c 80 80 90 C 60 c c c 68- 41-21(3046}λ TABU 5 tcontinued! PRggMgROBMCT TESTS PLANT INHIBITION Ϊ • A n s • D o B y M o c Θ V • 1 n w 1 Cpd. Rat· n b j b 9 9 b 1 B b No. kg/ha a 9 9 r r 1 u • U w 131 1.12 80 20 80 20 70 C 30 C 1 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 0 20 0 20 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 ISO 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 41-21(3046)A TABLE s fcontinued) PREEMERGENCE TESTS * PLANT INHIBITION ϊ a A n s a 0 o B Y K o c o V a I n w i Cpd. Rata n b J b 9 9 b 1 o b No. kg/ha a 9 9 r r 1 u a 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 * Wibw-THIN. A Exceaaive damping off t Observation ca. 4-weeks 0 1 0 0 0 0 0 0 0 0 0 41-21(3046)A POST-EMERGENCE HERBICIDE TESTS The post-emergence herbicidal activity of some of the various compounds of this invention was demon5 strated 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 below 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 1014 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. 41-21(3046)A IABL£_£ POST-EMERGENCE TESTS % PLANT INHIBITION Y • A n s '· D o B y M o C o V • I n W i Rat· Π b j b g 9 b 1 m b kg/ha a g g r r 1 u • u w 1.12 40 40 30 50 30 C C c 80 80 1.12 50 20 40 40 80 c c c 60 C 11.21 40 60 80 30 90 80 70 c 90 c 11.21 10 0 10 0 0 20 20 30 40 90 11.21 0 0 10 0 0 20 20 20 30 0 11.21 0 0 0 0 10 30 10 90 50 70 11.21 20 10 10 0 10 80 C C 90 c 11.21 20 10 60 10 0 20 20 C 70 60 1.12 0 10 30 20 30 90 90 90 80 80 11.21 0 20 20 0 20 80 80 c 50 60 11.21 40 90 90 c 90 C 90 c 90 C 11.21 30 90 C c C 90 C c C C 11.21 20 40 70 10 70 80 80 c 90 80 11.21 30 10 70 0 C C 80 c 80 70 11.21 20 20 50 30 40 60 60 c 70 C 11.21 30 80 90 90 C C C c C c 11.21 20 60 70 0 70 c 60 c 60 60 11.21 30 80 80 20 90 c 50 c 90 80 1.12 40 90 90 c C 90 C c 90 90 1.12 10 10 70 80 C c 60 c 90 70 11.21 60 90 90 40 80 c C c C C 1.12 20 0 40 30 30 90 90 c 80 70 -72- 41-21(3046)A TABLE 6 (continued) POST-EMERGENCE TESTS PLANT INHIBITION y • A n S • D o B y M o c o V • I n w i :pd. Rate n b j b 9 9 b 1 B b to. kg/ha a 9 9 r r 1 u • 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 β 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 8 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 so 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 8 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 β 1.12 20 10 20 0 30 C 90 C 70 C 59 8 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 SO 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 41-21(3046)A -73TABLE 6 (continued) POST-EMERGENCE TESTS 3 E £I J5SI £13 ΊΟΝ Y A s D B M C V I H e n a o y o o a Π i Cpd. Rate n b j b 9 9 b 1 n b No. kg/ha a 9 9 r r 1 u a u w 66 1.12 30 60 80 SO 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 so 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 10 90 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 60 90 C 90 90 90 c 86 1.12 10 30 20 30 20 60 50 C 50 90 41-21(3046,A TABLE 6 (continued) POST-EMERGENCE TESTS % PLANT INHIBITION Y A s D B M c V I W β n • o y o o • n i Cpd. Rat· n b j b g 9 b 1 m b No. kg/ha 9 9 r r 1 u • 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 0 20 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 -75- 41-21(3046)A TABLE 6 (continued) POST-EMERGENCE TESTS 4 PLANT INHIBITION Y • A ή S • 0 o B y M o C o V • I n H i Cpd. Rate n b j b 9 9 b 1 m b No. kg/ha • 9 9 r r 1 u • 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 so 60 117 e 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 -76- 41-21(3046)* TABLE 6 (continued) POST-EMERGENCE TESTS PLANT INHIBITION Y • λ n s * e 0 o B y M o C o V • I n W ί Cpd. Rate n b 3 b 9 9 b 1 m b No. kg/ha a 9 9 r r 1 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 e 11.21 10 0 0 0 10 20 20 40 40 20 146 β 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 e 11.21 0 0 0 0 0 10 10 10 0 40 150 8 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 -7741-21(3046)A TABLE 6 (continued) POST-EMERGENCE TESTS % PLANT INHIBITION Y A S 0 B M C V I W • n • o y o o • n 1 Cpd. Rat· n b J b 9 9 b I m b No. kg/ha a 9 9 r r 1 u • u w 152 11.21 0 0 0 0 0 0 0 0 0 0 153 11.21 10 10 10 0 20 40 30 80 80 C 154 1.12 20 C 80 80 70 70 80 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 reapona· * Duplicate teat -78- 41-21(3046)A 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 wetting agent, a dispersing agent, an emulsifying agent or any suitable combination of these.
Suitable wetting 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 powders are water-dispersible compositions containing one or more active ingredients, an inert solid extender and one or more wetting and dispersing agents. The inert solid 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 wettable powders compositions of this invention usually contain from above 0.5 to 60 parts -79- 41-21(3046)A (preferably from 5-20 parts) of active ingredient, from about 0.25 to 25 parts (preferably 1-15 parts) of wetting 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 waterinsoluble 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, Hmethylpyrrolidone, 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. -80- 41-21(3046)A 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, finely10 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, -8141-21(3046)A nitrophenyl ethers, diphenyl ethers, pyridines and the like such as: Heterocyclic Nitrooen/Sulfur Derivatives 2-Chloro-4-ethylamino-6-isopropylamino-£-triazine 5 2-Chloro-4,6-bis(isopropylamino)-g-triazine 2- Chloro-4,6-bis(ethylamino)-s-triazine 3- Isopropyl-lH-2,1,3-benzothiadiazin-4-(3H)-one 2,2dioxide 3-Amino-l,2,4-triazole 6,7-Dihydrodipyrido(l,2-:2·,l'-c)-pyrazidiinium salt -Bromo-3-isopropy1-6-methyluracil 1,l'-Dimethyl-4,4'-bypyridinium 2- (4-Isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-3quinolinecarboxylic acid Isopropylamine salt of 2-(4-isopropyl-4-methyl-5oxo-2-imidazolin-2-yl)nicotinic acid Methyl 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2yl)-m-toluate and methyl 2-(4-isopropyl-4-methyl5-oxo-2-imidazolin-2-yl)-p-toluate - (Trifluoromethyl)-4-chloro-3-(3'-(1-ethoxycarbonyl]ethoxy-4'-nitrophenoxy)-1-methylpyrazol; -(Trifluoromethyl)-4-chloro-3-(3'-methoxy-4'-nitrophenoxy) -1-methylpyrazole; -(Trifluoromethyl)-4-chloro-3-(3'-[l-butoxycarbonyl]25 ethoxy-4’-nitrophenoxy)-4-methylpyrazol; -(Trifluoromethyl)-4-chloro-3-(3 *-methylsulfamoylcarbonyl propoxy-4’-nitrophenoxy)-4-methylpyrazol; -(Trifluoromethyl)-4-chloro-3-(3·-propoxycarbonylmethyloxime-4'-nitrophenoxy)-1-methylpyrazole; (±) -2-(4-([5-(Trifluoromethyl)-2-pyridinyl)oxy]phenoxy]propanoic acid (9CI). .5- dimethyl-2-(difluoromethyl)-4-isobutyl-6trifluoromethyl-3,5-pyridinedicarbothioate; 3- Pyridinecarboxylic Acid, 2-(difluoromethyl)-5-(4,535 dihydro-2-thiazolyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-, methyl ester; 3.5- Pyridinedicarboxylic acid, 2-(difluoromethyl)-4-(2methylpropyl)-6-(trifluoromethyl)-, dimethyl ester; -82- 41-21(3046)* 3,5-Pyridinedicarbothioic acid, 4-(cyclopropylmethyl)-2(difluoromethyl)-6-(trifluoromethyl)-, S,S-dimethyl ester; Sulfoximine, N-(diethoxyphosphinyl)-S-methyl-S-pheny15 Ureas and Sulfonvlureas N-(4-Chlorophenoxy) phenyl-N,N-dimethylurea N, N-d ime thyl-N' - (3-chloro-4-methylphenyl) urea 3-(3,4-dichlorophenyl) -1,1-dimethy lurea l,3-Dimethyl-3-(2-benzothiazolyl) urea 3-(p-Chlorophenyl)-1,1-dimethylurea 1- Butyl-3- (3,4-dichlorophenyl) -l-methy lurea 2- Chloro-N[(4-methoxy-6-methyl-l,3,5-triazin-2-yl) aminocarbonyl]-benzenesulf onamide 15 Methyl 2-(((((4,6-dimethyl-2-pyrimidinyl)amino)carbonyl)amino)sulfonyl) benzoate Ethyl l-[methyl 2-(((((4,6-dimethyl-2-pyrimidinyl)amino)carbonyl)amino) sulfonyl) ] benzoate Methyl-2 ((4,6-dimethoxy pyrimidin-2-yl)aminocar20 bonyl)amino sulfonyl methyl) benzoate Methyl 2-(((((4-methoxy-6-methyl-l,3,5-triazin-2-yl)amino) carbonyl) amino) sulfonyl) benzoate N-( 3-(Ν,Ν-dimethylcarbamoyl) -2-pyridin-2-yl]sulfonylN * - (4,6-dimethoxypyrimidin-2-yl) urea N-[ (3-ethylsulfonyl)-2-pyridin-2-yl]-sulfonyl-N'-(4,6dimethoxy-pyr imidin-2-y 1) urea N-(2-methoxycarbonylphenyl sulfonyl)-Ν'-(4,6-bisdif luoromethoxypyrimidin-2-yl) urea Carbamates/Thiolcarbamates 30 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 -83- 41-21(3046)A Acetamldes/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)-25 chloroacetamide N-(lH-pyrazol-l-ylmethyl-N-(2,4-dimethylthien-3-yl)-2chloroacetamide N-(1-pyrazol-l-ylmethyl)-N-(4,6-dimethoxypyrimidin-5yl)-2-chloroacetamide N-(2,4-dimethy1-5-([[(trifluoromethyl)sulfonyl]amino]phenyl]acetamide N-Isopropyl-2-chloroacetanilide N-Isopropyl-l-(3,5,5-trimethylcyclohexen-l-yl)-2chloroacetamide 2’,6·-Diethyl-N-(butoxymethyl)-2-chloroacetanilide 21,6'-Diethyl-N-(2-n-propoxyethyl)-2-chloroacetanilide 2 ', 6'-Dimethy1-N-(1-pyrazol-l-ylmethyl)-2-chloroacetanilide 21,6’-Diethyl-N-methoxymethyl-2-chloroacetanilide 2’-Methyl-6'-ethy1-N-(2-methoxyprop-2-yl)-2-chloroacetanilide 2·-Methyl-6·-ethy1-N-(ethoxymethyl)-2-chloroacetanilide a,a,α-Trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine N-(1,1-dimethylpropynyl)-3,5-dichlorobenzamide Acids/Esters/Alcohols 2,2-Dichloropropionic acid 2- Methyl-4-chlorophenoxyacetic acid 2,4-Dichlorophenoxyacetic acid Methy1-2-[4-(2,4-dichlorophenoxy)phenoxy]propionate 3- Amino-2,5-dichlorobenzoic acid 2-Methoxy-3,6-dichlorobenzoic acid 2.3.6- Trichlorophenylacetic acid N-l-naphthylphthalamic acid Sodium 5-[2-chloro-4-(trifluoromethy1)phenoxy]-2n itrobenzoate 4.6- Dinitro-o-sec-butylphenol N-(phosphonomethyl)glycine and its salts -84- 41-21(3046)A Butyl (R) -2-(4-((5-(trifluoromethyl)-2-pyridinyl)oxy]phenoxy] propanoate Ethers 2,4-Dichlorophenol-4-nitrophenyl ether 5 2-Chloro-i,6,ί-trifluoro-p-tolyl-3-ethoxy-4-nitrodiphenyl ether -(2-chloro-4-trifluoromethylphenoxy)-N-methylsulfonyl 2-nitrobenazmide 1'-(Carboethoxy) ethyl 5-[2-chloro-4-(trifluoro10 methyl) 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, l-methyl-4-(l-methylethyl)-2-(2-methylphenyImethoxy) -, exoGlyphosate 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. -85- 41-21(3046)* Herbicidal formulations of the types described above are exemplified in several illustrative embodiments below.
I. Emulsifiable Concentrates Weight Percent A. Compound No. 22 Free acid of complex organic phosphate or aromatic or aliphatic hydrophobe base (e.g., GAFAC RE-610, registered trademark of GAF Corp.) Po ly oxy e thy 1 ene / po lyoxypr opy lene b 1 ock copolymer with butanol (e.g., Tergitol XH, registered trademark of Union Carbide Corp.) Xylene Monochlorobenzene B. Compound No. 36 Free acid of complex organic phosphate of aromatic or aliphatic hydrophobe base (e.g., GAFAC RE-610) Polyoxyethylene/polyoxypropylene block copolymer with butanol (e.g., Tergitol XH) Xylene Monochlorobenzene C. Compound No. 43 Free acid of complex organic phosphate or aromatic or aliphatic hydrophobe base (e.g., GAFAC RE-610, registered trademark of GAF Corp.) Polyoxyethylene/polyoxypropylene block copolymer with butanol (e.g., Tergitol XH, registered trademark of Union Carbide Corp.) Cyclohexanone Aromatic 200 4.0 3.5 1.5 .34 85.66 100.00 3.0 4.0 1.60 4.75 86.65 100.00 2.5 4.0 1.5 .5 36,.5 100.00 -8641-21(3046)A Weight Percent Compound of No. 52 Free acid of complex organic phosphate of aromatic or aliphatic hydrophobe 5.0 base (e.g., GAFAC RE-610 Polyoxyethy1ene/polyoxypropylene block 3.00 copolymer with butanol (e.g., Tergitol XH) 2.0 Phenol 5.0 Monochlorobenzene 85.0 100.00 Compound No. 53 Free acid of complex organic phosphate or aromatic or aliphatic hydrophobe base (e.g., GAFAC RE-610, registered 1.50 trademark of GAF Corp.) Polyoxyethylene/polyoxypropylene block 4.50 copolymer with butanol (e.g., Tergitol registered trademark of Union Carbide XH, Corp.) 1.00 Isophorone 5.34 Emerset 2301 87.68 100.00 Compound No. 54 Free acid of complex organic phosphate of aromatic or aliphatic hydrophobe 4.50 base (e.g., GAFAC RE-610 Polyoxyethylene/polyoxypropylene block 3.00 copolymer with butanol (e.g., Tergitol XH) 2.00 Cyclohexanone 4.75 γ-Butyrolactone 85,75 100.00 41-21(3046)A Weight Percent II. Flowables A. Compound No. 58 25.0 Xanthan Gum 0.3 Ethylene Glycol 10.0 Sodium lignosuIfonate 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 lignosuIfonate 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 -8841-21(3046)A Weight Percent III. Wettable Powders A. Compound No. 83 Sodium lignosulfonate Kaolin Amorphous silica (synthetic) B. Compound No. 85 Sodium dioctyl sulfosuccinate Alkyl Aryl Sulfonate Kaolin Amorphous silica (synthetic) C. Compound No. 93 Sodium lignosulfonate Sodium N-methyl-N-oleyl-taurate Amorphous silica (synthetic) Kaolinite clay D. Compound No. 96 Sodium lignosulfonate Sodium dioctyl sulfosuccinate Attapulgite clay Amorphous silica (synthetic) E. Compoud No. 102 Sodium dioctyl sulfosuccinate Sodium lignosulfonate Kaolin Amorphous silica synthetic F. Compound No. 106 Sodium lignosulfonate Sodium N-methyl-N-oleyl-taurate Amorphous silica (synthetic Kaolinite clay .0 .0 60.0 *0 100.0 80.0 1.5 3.5 5.0 19.Q 100.0 .0 3.0 1.0 .0 76.0 100.0 .0 4.0 1.0 60.0 ..5^ 100.0 75.0 1.25 3.0 .75 IQ.t.O 100.0 .0 3.0 1.0 .0 71,0 100.0 -89- 41-21(3046)A IV. Granules Weight Percent A. Compound No. 36 Dipropylene Glycol ' 15.0 5.0 5 Granular attapulgite (24/48 mesh) 80.0 100.0 10 B. Compound No. 43 Ethylene Glycol (24/48 mesh) Granular Montmorillonite 5.0 15.0 S1L_£> 100.0 C. compound No. 49 Ethylene glycol Granular Pyrophyllite (24/48 mesh) 1.0 5.0 94.0 100.0 15 D. Compound No. 52 Dipropylene Glycol Granular Pyrophyllite (24/48 mesh) 5.0 15.0 80.0 100.0 E. Compound No. 53 20.0 20 Granular Bentonite (24/48 mesh) 80.0 100.0 F. Compound No. 54 Amorphous silica (synthetic) Granular Montmorillonite (24/48 mesh) 20.0 1.0 79.0 25 100.0 G. Compound No. 58 Ethylene glycol Granular Montmorillonite (24/48 mesh) 5.0 10.0 100.0 30 H. Compound No. 59 Dipropylene Glycol Granular Bentonite (30/60 mesh) 10.0 10.0 8Q«.Q 100.0 90- 41-21(3046)A Weight Percent V, Suspension Concentrates A. Compound No. 66 32.5 Sodium Naphthalene-Formaldehyde Condensate (Morwet D-425) 3.0 Propylene Glycol 10.0 Sodium Diisopropyl Naphthalene Sulfonate (Morwet IP) l.o 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) l.o 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.o 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 -9141-21(3046)A Compound No. 93 Nonylphenol ethoxylate 9.5 mole EO Sterox NJ Sodium lignosuIfonate (Reax 88B) Ethylene Glycol Xanthan Gum Water Compound No. 96 Sodium lignin sulfonate (Polyfon F) Ethylene Glycol Xanthan Gum Water Weight Percent 33.0 l.o 4.0 10.0 0.2 Six ? 100.0 34.0 .0 .0 0.1 45.9 100.0 .0 Compound No. 102 Sodium Naphthalene Sulfonate formaldehyde Condensate Propylene Glycol Snelling Grade Bentonite Antifoam Water VI Microcapsules (Active ingredient encapsulated within polymeric shell wall) Compound No. 69 Polyurea shell wall Reax· 88B (dispersant) NaCl (electrolyte) Water .0 7.0 0.5 0.5 52.0 100.0 4.0 0.4 1.0 .0 100.00 -9241-21(3046)A B C D E F Compound No. 81 Weight Percent 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 Compound No. 130 100.00 1.0 Polyurea shell wall 7.0 Reax· C-21 2.0 NaCl 10.0 Xylene 40.0 Water 40.0 Compound No. 63 100.0 48.0 Polyurea shell wall 4.8 Reax· 88B 3.0 NaCl 15.0 Kerosene 29-i2 Compound No. 74 100.0 40.0 Polyurea shell wall 6.5 Reax· 88B 2.0 NaNOj 10.5 Solvent 25.0 Water 16.0 Compound No. 157 100.0 10.0 Polyurea shell wall 8.5 Reax· C-21 1.5 NaCl 6.0 Solvent 20.0 Water 54t0 100.0 -93- 41-21(3046) λ 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, λ 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 he 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 may 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 -94- 41-21(304«)* ft invention, and it is understood that such equivalent embodiments are part of this invention.

Claims (35)

1. WE CLAIM
1. Compounds according to Formula I: io Ri tuted with optionally *2 R 4 member; is hydrogen, C V5 alkyl optionally substian R 4 member; Cj. e cycloalkyl or cycloalkenyl substituted with C V4 alkyl; is C v5 alkyl optionally substituted with an Rj is hydrogen or halogen and R 4 is hydrogen, C ve alkyl, haloalkyl, alkylthio, alkoxyalkyl or polyalkoxyalkyl, Cj. e cycloalkyl, cycloalkenyl, cycloalkyalkyl or cycloalkenylalkyl; C 2 . B alkenyl or alkynyl; carbamyl, halogen, amino, nitro, cyano, hydroxy, C 4 . 10 heterocycle containing 1-4 0, S(0) m and/or N hetero atoms, C 6 . 12 aryl, aralkyl or alkaryl, -CXYRj, -CXR,, -CH 2 OCOR 10 , -YR n , -NR 12 R 13 , or any two R 4 members may be combined through a saturated and/or unsaturated carbon, -C- and/or hetero atom linkage to form a heterocyclic ring having up to 9 ring members, which may be substituted with any of said R 4 members or where not self-inclusive said R 4 or Rg. 13 members substituted with any of said R 4 members; provided that when said two R 4 members are combined through a -hetero atom -i-N- linkage, said heterocyclic ring has at least six ring members; X is O# S(O)„, NRj 4 or CRjjRj 4 ; Y is O or S(O) a or NR, 7 ; R 8 -R 17 are one of said R 4 members; m is 0-2 and n is 0-5. -9β- 41-21(304«)*
2. Compounds according to Formula II wherein R,, Rj and Rj are as defined for Formula I; 10 Rj is independently one of said R 3 members and R* and R z are independently one of said R* members or are combined to form a heterocyclic ring having up to 9 members and containing Ο, N and/or S atoms, which ring may be substituted with alkyl, 15 haloalkyl, alkoxy, alkenyl or alkynyl radicals each having up to 4 carbon atoms; provided that when said two R 6 and R 7 members are combined through a -hetero atom II -C-N- linkage, said heterocyclic ring has at least six 20 ring members.
3. Compounds according to Formula III I «1 30 wherein R 1 and Rj are C vs alkyl; Rj and Rj are hydrogen, bromo, chloro or fluoro; Rj is an Rj member or nitro; R 7 is an R 4 member or Rj and R r are combined through an -OCH 2 (C-O)-N(Rj)-linkage to form a fused six-membered ring. -97- 41-2l(3046)A
4. Compounds according to Claim 3 wherein R, and R z are methyl; Rj is hydrogen, bromo or chloro; R, is chloro or fluoro; 5. R 6 is chloro, fluoro, or nitro; R 7 is a YR n member as defined in Formula I or Rj and R 7 are combined through an -OCH Z (C=O)N-(propyny1)-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)l-methyl-5-(methylsulfonyl)-lH-pyrazole 15 4-Bromo-3-(2-fluoro-4-chloro-5-(2-propynyloxy)phenyl)l-methyl-5-(methylsulfonyl)-lH-pyrazole 4-Chloro-3-(2-fluoro-4-chloro-5-(2-methoxyethoxy)phenyl)-l-methyl-5-(methylsulfonyl)-lH-pyrazole 4-Bromo-3-(2-fluoro-4-chloro-5-(2-methoxyethoxy)20 phenyl)-l-methyl-5-(methylsulfonyl)-lH-pyrazole 6. -(4-Chloro-l-methyl-5-(methylsulfonyl)-lH-pyrazol-3yl)-7-fluoro-4-(2-propynyl)-2H-1,4-benzoxazin-3(4H)-one (5-(4-Bromo-l-methyl-5-(methylsulfonyl)-lH-pyrazol-325 yl)-2-chloro-4-fluorophenoxy)acetic acid, 1methylethyl ester (5-(4-Chloro-1-methy1-5-(methylsulfonyl)-lH-pyrazol-3yl)-2-chloro-4-fluorophenoxy)acetic acid, 1methylethyl ester 30 2-(5-(4-Bromo-l-methyl-5-(methylsulfonyl)-lH-pyrazol-3y1)-2-chloro-4-fluorophenoxy) propanoic acid, ethyl ester and 2-(5-(4-Chloro-l-methy1-5-(methylsulfonyl)-lH-pyrazol3-yl)-2-chloro-4-fluorophenoxy)propanoic acid, 35 ethyl ester. -S8- 41-21(3046)*
6. 4-Chloro-3-(2- fluoro-4-chloro-5-(2propynyloxy)phenyl) -l-methyl-5-(methylsulfonyl) -1Hpyrazole.
7. 4-Bromo-3-(2-fluoro-4-chloro-5-(25 propynyloxy) phenyl) -l-methyl-5- (methylsulfonyl) -1Hpyrazole.
8. 2-(5-(4-Chloro-l-methyl-5-(methylsulfonyl) -lH-pyrazol-3-yl)-2-chloro-4-fluorophenoxy)propanoic acid, ethyl ester.
9. 10 9. (5-(4-Chloro-l-methyl-5-(methylsulfonyl)lH-pyrazol-3-yl)-2-chloro-4-fluorophenoxy)acetic acid, l-methylethyl ester. 10. Herbicidal composition comprising an adjuvant and a herbicidally effective amount of a 15 compound according to Formula I: 20 R, wherein R, is hydrogen, C vs alkyl optionally substituted with an R 4 member; Cj. e cycloalkyl or cycloalkenyl optionally substituted with C V4 alkyl; 25 Rj is C v5 alkyl optionally substituted with an R 4 member; R 3 is hydrogen or halogen and R 4 is hydrogen, C V8 alkyl, haloalkyl, alkylthio, alkoxyalkyl or polyalkoxyalkyl, Cj. 8 cycloalkyl, 30 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(0) a and/or N hetero atoms, c 8 . 12 aryl, aralkyl or alkaryl, —CXYR 8 , — CXR?, —CH 2 OCOR^ 8 , — YRjj, — NR 32 Rjj, or any two R 4 35 members may be combined through a saturated and/or X unsaturated carbon, - -99- 41-21(3046)A which may be substituted vith any of said Rj members or where not self-inclusive said R 4 or Rj. 13 members substituted vith any of said R 4 members; provided that when said tvo R 4 members are combined through a -hetero 5 ί atom -C-N- linkage, said heterocyclic ring has at least six ring members; X is 0, S(O) a , NR 14 or CR,jR, 8 ; Y is 0 or S(0) B or NR, 7 ; 10 Rj-R 17 are one of said R 4 members; m is 0-2 and n is 0-5.
10. 11. Herbicidal composition comprising an 15 adjuvant and a herbicidally-effective amount of a compound according to Formula II: Rs wherein R,, Rj and R 3 are as defined for Formula I; 25 Rj is independently one of said R 3 members and Rj and R 7 are independently one of said R 4 member* or are combined to form a heterocyclic ring having up to 9 members and containing Ο, N and/or S atom*, which ring may be substituted with alkyl, 30 haloalkyl, alkoxy, alkenyl or alkynyl radicals each having up to 4 carbon atoms; provided that when said two Rj and R 7 members are combined through a -hetero atom -C-N- linkage, said heterocyclic ring has at least six 35 ring members. -10041-21(3046)A
11. 12. Herbicidal compositions comprising an adjuvant and a herbicidally-effective amount of a compound according to Formula III: 10 R, wherein R, and R 2 are σ ν5 alkyl; R 3 and Rj are hydrogen, bromo, chloro or fluoro;
12. 15 R 6 is an Rj member or nitro; R 7 is an R 4 member or R 6 and R 7 are combined through an -OCH 2 (C=O)N-(R 4 )-linkage to form a fused six-membered ring. 20 13. Composition according to Claim 12 wherein in said compound: R, and R 2 are methyl; R 3 is hydrogen, bromo or chloro; Rj is chloro or fluoro; 25 R$ is chloro, fluoro or nitro; R 7 is a YR n member as defined in Formula I or R 6 and R 7 are combined through an OCH 2 (C=O)N-(propynyl)-linkage to give a fused 6-membered ring. 30 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)pheny1) l-methyl-5-(methylsulfonyl)-lH-pyrazole 4-Bromo-3-(2-fluoro-4-chloro-5-(2-propynyloxy)pheny1) 35 l-methyl-5-(methylsulfonyl)-lH-pyrazole 4-Chloro-3-(2-fluoro-4-chloro-5-(2-methoxyethoxy) phenyl)-l-methyl-5-(methylsulfonyl)-lH-pyrazole -101- 41-21(3046)A 4-Bromo-3-(2-fluoro-4-chloro-5-(2-methoxyethoxy)phenyl)-l-methyl-5-(methylsulfonyl)-lH-pyrazole 6-(4-Chloro-l-methyl-5-(methylsulfonyl)-lH-pyrazol-3yl)-7-fluoro-4-(2-propynyl)-2H-1,4-benzoxazin-35 (4H)-one (5-(4-Bromo-l-methy1-5-(methylsulfonyl)-lH-pyrazol-3yl)-2-chloro-4-fluorophenoxy)acetic acid, 1methylethyl ester (5-(4-Chloro-l-methyl-5-(methylsulfonyl)-lH-pyrazol-310 yl)-2-chloro-4-fluorophenoxy)acetic acid, 1methylethyl ester 2- (5-(4-Brorao-l-methyl-5-(methylsulfonyl)-lH-pyrazol-3yl)-2-chloro-4-fluorophenoxy)propanoic acid, ethyl ester and 15 2-(5-(4-Chloro-l-methyl-5-(methylsulfonyl)-lH-pyrazol3-yl)-2-chloro-4-fluorophenoxy)propanoic acid, ethyl ester. 15. Herbicidal composition comprising an adjuvant and a herbicidally-effective amount of 420 chloro-3-[1-fluoro-4-chloro-5-(2-propynyloxy)phenyl-lmethyl-5-(methylsulfonyl)-lH-pyrazole.
13. 16. Herbicidal composition comprising an adjuvant and a herbicidally-effective amount of 4-Bromo3- (2-fluoro-4-chloro-5-(2-propynyloxy)phenyl)-1-methy125 5-(methylsulfonyl)-lH-pyrazole.
14. 17. Herbicidal composition comprising an adjuvant and a herbicidally-effective amount of 2-(5(4-Chloro-l-methyl-5-(methylsulfonyl)-lH-pyrazol-3-yl)2-chloro-4-fluorophenoxy)-propanoic acid, ethyl ester. 30
15. 18. Herbicidal composition comprising an adjuvant and a herbicidally-effective amount of (5-(4Chloro-l-methyl-5-(methylsulfonyl)-lH-pyrazol-3-yl) -2chloro-4-fluorophenoxy)acetic acid, 1 methylethyl ester.
16. 19. Method for combatting undesirable plants in 35 crops which comprises applying to the locus thereof a herbicidally effective amount of a compound according to Formula I: -10241-21(3046)λ wherein R, is hydrogen, C v5 alkyl optionally substituted with an R 4 member; C 3 . e cycloalkyl or cycloalkenyl 10 optionally substituted with C V4 alkyl; Rj, is C,. 5 alkyl optionally substituted with an R 4 member; R 3 is hydrogen or halogen and R 4 is hydrogen, C v8 alkyl, haloalkyl, alkyl15 thio, alkoxyalkyl or polyalkoxyalkyl, C 3 . 8 cycloalkyl, cycloalkenyl, cycloalky alkyl or cycloalkenyl alkyl; C 2 . 8 alkenyl or alkynyl; carbamyl, halogen, amino, nitro, cyano, hydroxy, C 4 . 50 heterocycle containing 1-4 0, S(0)„ and/or N hetero atoms, C 6 . 12 aryl, aralkyl or alkaryl,
17. 20 -CXYRg, -CXR,, -CH 2 OCOR 10 , -YR„, -NR 12 R, 3 , or any two R 4 members may be combined through a saturated and/or X H unsaturated carbon, -C- and/or hetero atom linkage to form a heterocyclic ring having up to 9 ring members, 25 which may be substituted with any of said R 4 members or where not self-inclusive said R 4 or Rg. 13 members substituted vith any of said R 4 members; provided that when said two R 4 members are combined through a -hetero ί 30 atom -C-N- linkage, said heterocyclic ring has at least six ring members; X is O, S(0)., NR W or CR 13 R 18 ; Y is O or S(0) a or NR 17 ; R 8 -R 17 are one of said R4 members; m is 0-2 and n is 0-5. -103- 41-
18. 21(3046)A 20. Method for combatting undesirable plants in crops which comprises applying to the locus thereof a herbicidally-effective amount of a compound according to Formula II: 5 *s wherein R v Rj and R } are as defined for Formula I; Rj is independently one of said R } members and Rj and R 7 are independently one of said R 4 15 members or are combined to form a heterocyclic ring having up to 9 members and containing 0, 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 20 Rj and R 7 members are combined through a -hetero atom -C-N- linkage, said heterocyclic ring has at least six ring members. 25 21. Method of combatting undesirable plants in crops which comprises applying to the locus thereof a herbicidally-effective amount of a compound according to Formula III: 35 R, wherein -10441-21(3046)A R, and R 2 are c t . s alkyl; Rj and Rj are hydrogen, bromo, chloro or fluoro; R 6 is an Rj member or nitro; r 7 is an R 4 member or 5 R 6 and R 7 are combined through an -OCH 2 (C=O)-N(R 4 )-linkage to form a fused six-membered ring.
19. 22. Method according to Claim 21 wherein in said compound: 10 R, and R 2 are methyl; Rj is hydrogen, bromo or chloro; Rj is chloro or fluoro; R 6 is chloro, fluoro, or nitro; R 7 is a YR n member as defined in Formula I or 15 Rj and R 7 are combined through an -OCH 2 (C=O)N-(propynyl)-linkage to give a fused 6-membered ring.
20. 23. Method according to Claim 19 wherein said compound is selected from the group consisting of 20 4-Chloro-3-(2-fluoro-4-chloro-5-(2-propynyloxyJphenyl)l-methyl-5-(methylsulfonyl)-lH-pyrazole 4-Bromo-3-(2-fluoro-4-chloro-5-(2-propynyloxy)pheny1) l-methyl-5-(methylsulfonyl)-lH-pyrazole 4-Chloro-3-(2-fluoro-4-chloro-5-(2-methoxyethoxy)25 phenyl)-l-methyl-5-(methylsulfonyl)-lH-pyrazole 4-Bromo-3-(2-fluoro-4-chloro-5-(2-methoxyethoxy)phenyl)-l-methyl-5-(methylsulfonyl)-lH-pyrazole 6-(4-Chloro-l-methyl-5-(methylsulfonyl)-lH-pyrazol-3yl)-7-fluoro-4-(2-propynyl)-2H-l,4-benzoxazin-330 (4H)-one (5-(4-Bromo-l-methyl-5-(methylsulfonyl)-lH-pyrazol-3yl)-2-chloro-4-fluorophenoxy)acetic acid, 1methylethyl ester (5-(4-Chloro-l-methyl-5-(methylsulfonyl)-lH-pyrazol-335 yl)-2-chloro-4-fluorophenoxy)acetic acid, 1methylethyl ester -10541-21(3046)A 2-(5-(4-Bromo-l-methy 1-5-(methylsulfonyl) -lH-pyrazol-3yl) -2-chloro-4-f luorophenoxy Jpropanoic acid, ethyl ester 2-( 5-(4-Chloro-l-methyl-5-(methylsulfonyl) -lH-pyrazol5 3-yl)-2-chloro-4-fluorophenoxy)propanoic acid, ethyl ester.
21. 24. Method of combatting undesirable plants in crops which comprises applying to the locus thereof a herbicidally-effective amount of 4-chloro-3-(2-fluoro10 4-chloro-5-(2-propynyloxy) phenyl)-l-methyl-5-(methylsulfonyl) -lH-pyrazole.
22. 25. Process for the preparation of compounds according to Formula I which comprises reacting a compound according to Formula B with an oxidizing agent 15 according to the equation wherein R, is hydrogen, C,. 5 alkyl optionally substi25 tuted with an R 4 member; Cj. 8 cycloalkyi or cycloalkenyl optionally substituted with C V4 alkyl; Rj is C,. s alkyl optionally substituted with an Rj member; Rj is hydrogen or halogen and 30 Rj is hydrogen, C V8 alkyl, haloalkyl, alkylthio, alkoxyalkyl or poly alkoxy alkyl, Cj.j cycloalkyi, cycloalkenyl, cycloalkyalkyl or cycloalkenylalkyl; Cj. 8 alkenyl or alkynyl; carbamyl, halogen, amino, nitro, cyano, hydroxy, c 4 . 10 heterocycle containing 1-4 O, S(O) a 35 and/or N hetero atoms, C 6 . 12 aryl, aralkyl or alkaryl, -CXYRj, -CXRj, —CHjOCOR 10 , -YR,,, -NR 12 R 13 , or any two Rj members may be combined through a saturated and/or -106- 41-21(3046)A X II unsaturated carbon, -C- and/or hetero atom linkage to form a heterocyclic ring having up to 9 ring members, which may be substituted with any of said R 4 members or 5 where not self-inclusive said R* or Rj. 13 members substituted with any of said R 4 members; provided that when said two R 4 members are combined through a -hetero II atom -C-N- linkage, said heterocyclic ring has at least 10 six ring members; X is 0, S(O) B , NR U or CRjjR^j; Y is 0 or SfO),, or NR 17 ; Rg-R 17 are one of said R 4 members; m is 0-2 and 15 n is 0-5.
23. 26. Process according to Claim 25 wherein said compounds according to Formula I are those as defined for Formula II 20 wherein Rj, Rj and R 3 are as defined for Formula I; Rj is independently one of said Rj members and Rj and R 7 are independently one of said R4 30 members or are combined to form a heterocyclic ring having up to 9 members and containing Ο, 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 35 Rj and R 7 members are combined through a -hetero atom -10741-21(3046)A O -C-N- linkage, said heterocyclic ring has at least six ring members;
24. 27. Process according to Claim 25 wherein 5 said compounds according to-Formula 1 are those as defined for Formula III wherein 15 R, and R 2 are C,. 5 alkyl; Rj and Rj are hydrogen, bromo, chloro or fluoro; Rj is an Rj member or nitro; R 7 is an R 4 member or 20 R 6 and R 7 are combined through an -OCH 2 (C=O)N-(R 4 )-linkage to form a fused six-membered ring.
25. 28. Process according to Claim 27 wherein Rj and R 2 are methyl; Rj is hydrogen, bromo or chloro; Rj is chloro or fluoro; R* is chloro, fluoro or nitro and R 7 is a YRjj member as defined in Formula I
26. 29. Process for the preparation of compounds according to Formula I wherein Rj is a halogen, which comprises reacting a Formula I compound wherein R 3 is hydrogen with a halogenating agent.
27. 30. Process according to Claim 29 wherein said Formula I compounds prepared by the halogenation process are those as defined for Formula III wherein R } is halogen. -108- 41-21(304«)*
28. 31. Process according to Claim 30 wherein R, and R 2 are methyl, R$ is chloro or fluoro and R* is chloro, fluoro or nitro.
29. 32. Process for the preparation of compounds 5 according to Formula I wherein one of said R 4 members is -YRn end R n is not hydrogen, which comprises reacting the corresponding compound of Formula I wherein R 15 is hydrogen with an acylating or alkylating agent.
30. 33. Process according to Claim 32 wherein 10 said compound of Formula I prior to said acylation or alkylation is a compound as defined for Formula III wherein R 7 is “YH.
31. 34. A compound as defined in any of Claims 1, 2 or 3, substantially as described herein by way of Example. 15
32. 35. A herbicidal composition comprising a compound according to Claim 34, substantially as described herein by way of Example.
33. 36. A method for treating crops, substantially as described herein by way of Example. 20
34. 37. A process for preparing a compound as defined in any of Claims 1, 2 or 3, substantially as described herein by way of Example.
35. 38. A compound prepared by the process of Claim 37.
IE278591A 1990-08-06 1991-08-06 Herbicidal substituted aryl alkylsulfonyl pyrazoles IE912785A1 (en)

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Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5532416A (en) * 1994-07-20 1996-07-02 Monsanto Company Benzoyl derivatives and synthesis thereof
TR26599A (en) * 1992-03-17 1995-03-15 Monsanto Co MUSIC WEAR KILLER (HERBISID), SUBSTITUTED ARIL- HALOALKILPIRAZOLES.
AU653299B2 (en) * 1993-02-06 1994-09-22 Nihon Nohyaku Co., Ltd. A herbicidal composition having a reduced phytotoxicity
MY111038A (en) * 1993-10-12 1999-07-31 Nihon Nohyaku Co Ltd An improved pesticidal aqueous suspension concentrate and a process for production thereof.
US5880290A (en) * 1994-01-31 1999-03-09 Monsanto Company Preparation of substituted 3-aryl-5-haloalkyl-pyrazoles having herbicidal activity
DE4417837A1 (en) * 1994-05-20 1995-11-23 Basf Ag Substituted 3-phenylpyrazoles
DE4419517A1 (en) * 1994-06-03 1995-12-07 Basf Ag Substituted 3-phenylpyrazoles
GB9413237D0 (en) * 1994-07-01 1994-08-24 Zeneca Ltd Herbicides
US5587485A (en) * 1994-07-20 1996-12-24 Monsanto Company Heterocyclic- and carbocyclic- substituted benzoic acids and synthesis thereof
US5869688A (en) * 1994-07-20 1999-02-09 Monsanto Company Preparation of substituted 3-aryl-5-haloalkyl-pyrazoles having herbicidal activity
GB9422708D0 (en) * 1994-11-10 1995-01-04 Zeneca Ltd Herbicides
EP0751130A4 (en) * 1995-01-12 1998-07-08 Otsuka Kagaku Kk 4,5-dihydropyrazole-5-thione derivatives and acaricide containing the same
US6103667A (en) * 1995-06-15 2000-08-15 Novartis Corporation Phenylpyrazole herbicides
MX9710042A (en) * 1995-06-15 1998-03-29 Novartis Ag Novel herbicides.
DE19524623A1 (en) * 1995-07-06 1997-01-09 Basf Ag 5-pyrazolylbenzoic acid derivatives
US5739083A (en) * 1995-10-13 1998-04-14 Otsuka Kagaku Kabushiki Kaisha Pyrazole derivatives and insecticidal compositions containing the derivative as active component
DE19542520A1 (en) * 1995-11-15 1997-05-22 Basf Ag Substituted 1-methyl-3-phenylpyrazole
US5698708A (en) * 1996-06-20 1997-12-16 Monsanto Company Preparation of substituted 3-aryl-5-haloalkyl-pyrazoles having herbicidal activity
DE59708674D1 (en) 1996-08-01 2002-12-12 Basf Ag SUBSTITUTED 3-PHENYLPYRAZOLE
US6054413A (en) * 1996-09-19 2000-04-25 Basf Aktiengesellschaft 1-sulfonyl-3-phenylpyrazoles and their use as herbicides and for desiccating or defoliating plants
KR20000053201A (en) 1996-11-12 2000-08-25 한스 루돌프 하우스, 헨리테 브룬너, 베아트리체 귄터 Pyrazole derivatives useful as herbicides
UA53679C2 (en) 1996-12-16 2003-02-17 Басф Акцієнгезелльшафт Substituted pyrazole-3-yl benzazoles, a process for preparation thereof (variants), a herbicide agent and a process for preparation thereof, an agent for plants desiccation and/or defoliation and a process for undesirable plants growth control and a process for plants desiccation and/or defoliation
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DE19803395A1 (en) * 1998-01-29 1999-08-05 Bayer Ag Substituted heteroarylmethyl compounds
DE19838706A1 (en) 1998-08-26 2000-03-02 Bayer Ag Substituted 3-aryl-pyrazoles
AU7284200A (en) * 1999-09-10 2001-04-17 Basf Aktiengesellschaft Substituted pyrazol-3-ylbenzoxazinones
EP1289970A1 (en) * 2000-05-15 2003-03-12 Basf Aktiengesellschaft 3-arylisothiazoles and their use as herbicides
EP2430920B1 (en) 2007-04-03 2016-11-16 E. I. du Pont de Nemours and Company Substituted benzene fungicides
US8669208B2 (en) 2010-10-01 2014-03-11 Basf Se Herbicidal benzoxazinones
CA2939176A1 (en) 2014-02-21 2015-08-27 Basf Se Aqueous agroformulation comprising suspended pesticide, cellulose ether and thickener

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2409753A1 (en) * 1974-03-01 1975-09-11 Basf Ag SUBSTITUTED PYRAZOLES

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