AU649474B2

AU649474B2 - Herbicidal substituted aryl alkylsulfonyl pyrazoles

Info

Publication number: AU649474B2
Application number: AU84146/91A
Authority: AU
Inventors: Gerard Anthony Dutra; Bruce Cameron Hamper; Deborah Aileen Mischke; Kurt Moedritzer; Michael David Rogers; Scott Santford Woodard
Original assignee: Monsanto Co
Current assignee: Monsanto Co
Priority date: 1990-08-06
Filing date: 1991-08-02
Publication date: 1994-05-26
Anticipated expiration: 2011-08-02
Also published as: EP0542872A1; IL99104A0; BG97409A; HUT63542A; PT98592A; FI930506A; WO1992002509A1; CN1061221A; NZ239269A; CA2087260A1; JPH05509103A; FI930506A0; YU162291A; IE912785A1; AU8414691A; BR9106737A; HU9300307D0; MX9100557A

Description

OPI DATE 02/03/92 AOJP DATE 09/04/92 APPLN. ID 84146 91 PCT NUMBER PCT/tlS91/05530 N TREATY(PCT) INTERI (51) International Patent Classification 5 (11) International Publication Number: WO 92/02509 CO7D 231/18, 403/04, 417/04 Al CO7D 413/04, 409/04 (43) International Publication Date: 20 February 1992 (20.02.92) (21) International Application Number: PCT/US91/05530 (74) Agent: BOLDING, James, Clifton; Monsanto Company, 800 North Lindbergh Boulevard, St. Louis, MO 63167 (22) International Filing Date: 2 August 1991 (02.08.91) (US).

Priority data: (81) Designated States: AT (European patent), AU, BE (Euro- 563,479 6 August 1990 (06.08.90) US pean patent), BG, BR, CA, CH (European patent), CS, 735,091 29 July 1991 (29.07.91) US DE (European patent), DK (European patent), ES (European patent), FI, FR (European patent), GB (Euro- (71) Applicant: MONSANTO COMPANY [US/US]; 800 pean patent), GR (European patent), HU, IT (European North Lindbergh Boulevard, St. Louis, MO 63167 patent), JP, KR, LU (European patent), NL (European patent), PL, AO, SE (European patent), SU.

(72) Inventors: MISCHKE, Deborah, Aileen 25 White River Lane, Defiance, MO 63341 HAMPER, Bruce, Published Cameron 132 Wildwood Lane, Kirkwood, MO 63122 With intenational search report.

WOODARD, Scott, Santford 1208 Cottage Mill Before the expiration of the time limit for amending the Drive, Ballwin, MO 63021 MOEDRITZER, Kurt claims and to be republished in the event of the receipt of 408 Belleview, Webster Groves. MO 63119 ROG- amendments.

ERS, Michael, Da-id 12465 Dawn Hill Drive, Maryland Heights, MO 63043 DUTRA, Gerard, Anthony 10445 Whitebridge Lane, St. Louis, MO 63141 649474 (54) Title: HERBICIDAL SUBSTITUTED ARYL ALKYLSULFONYL PYRAZOLES (57) Abstract The invention herein relates to certain substituted-arylpyrazole compounds, herbicidal compositions containing same, herbicidal methods of use and processes for preparing said compounds.

See back of page WO 92/02509 P(J/US91/05530 -1- 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 type compounds are known in the literature. Such compounds have various utilities, 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 heterocyclic, thienyl or alkyl-substituted furanyl, pyridyl, pyrimidinylurea, etc. and the pyrazolyl radical is substituted in various positions on the N or carbon atoms with alkyl, halogen, alkoxy, heterocycles, S(O),R 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.

SUBSTITUTE

SHEET

WO 92/02509 PCT/US91/05530 -2- SUMMARY OF THE INVENTION This invention relates to herbicidally-active compounds, compositions containing these compounds, processes for making them and herbicidal methods of using same., In a first aspect the present invention provides compounds according to Formula II:

__II

R N

RI

wherein RI is hydrogen, C 1 5 alkyl optionally substituted with hydrogen or.a R or R, member; C3, cycloalkyl optionally substituted with C, alkyl;

R

2 is C-.5 alkyl optionally substituted with hydrogen or an R or R, member; RR is hydrogen or halogen; R, is halogen and Rs and R7 are C 18 alkyl, haloalkyl, alkylthio, alkoxyalkyl or polyalkoxyalkyl, Cg cycloalkyl, cycloalkenyl, cycloalkyalkyl or cycloalkenylalkyl; C 2 .8 alkenyl or alkynyl; carbamyl, halogen, amino, nitro, cyano, hydroxy, C410 heterocycle containing 1-4 0, S(0)m and/or N hetero atoms, C& 1 2 aryl, aralkyl or alkaryl, -CXYRg, -CXRP,

-CH

2

OCOR

0 i, -YR 11

-NR

12

R

13 or any two ccnbinable R 6 and R members may be combined through a saturated and/or unsaturated carbon, x £4 II 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 5

-R

7 members or where not self-inclusive said

R,-R

7 or R,-Ri3 members substituted with any of said R-C, ,ryz P? members; provided that when said two cobinable R and PR7 embers are p 1 2A combined through a -hetero atom linkage, said heterocyclic ring has at least six ring members; X is 0, S(0)m, NR 1 4 or CRSR 16 Y is 0 or S(0)mor NR 1 7 *Rg-R 1 7 are one of said R 5

-R

7 members, and m is 0-2.

In a second aspect the present invention provides a process for the preparation of compounds according to Formula II which comprises reacting a compound according to Formula B with an oxidizing agent according to the equation SR 5 R, S2 soxidation S 6N 6- N 'N 0 R7 B

R

R II wherein RI is hydrogen, C,.

5 alkyl optionally substituted with an R 7 member; C38 cycloalkyl or cycloalkenyl optionally substituted with C, alkyl;

R

2 is Ci.5 alkyl optionally substituted with an R 7 member;

R

3 is hydrogen or halogen; R is halogen and 5 Rg and R7 are independently hydrogen, C1-8 alkyl, haloalkyl, alkylthio, alkoxyalkyl or polyalkoxyalkyl, C, cycloalkyl, cycloalkenyl, cycloalkyalkyl or cycloalkenylalkyl; C 2 alkenyl -e 2B or alkynyl; carbamyl, halogen, amino, nitro, cyano, hydroxy, Co 10 heterocycle containing 1-4 0, S(0)m and/or N hetero atoms, C 1 2 aryl, aralkyl or alkaryl, -CXYRg, -CXR9,

-CH

2 OCORio, -YRn, -NR12R3I, or any two cmbinable R 6 and P7 members may be combined through a saturated and/or unsaturated carbon

X

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 7 members or where not self-inclusive said R 7 or R,-R 13 members substituted with any of said R members; provided that when said two combinable R 6 and R7 members are combined through a 0 -hetero atom linkage, said heterocyclic ring has at least six ring members; X is O, S(0)m, NR, 4 or CRiRi 6 Y is 0 or S(0)mor NR, 7

R%-R,

7 are one of said R 7 members; m is 0-2 and n is In a third aspect the present invention provides herbicidal compositions comprising an adjuvant and a herbicidally effective amount of a compound according to the first aspect of the present invention; or of.a compound prepared according to the second aspect of the present invention.

*r* e 2C In a fourth aspect the present invention provides a method for combatting undesirable plants in crops which comprises applying to the locus thereof a herbicidally effective amount of a compound according to the first aspect of the present invention, or of a compound prepared according to the second aspect of the present invention, or of a composition according to the third aspect of the present invention.

In a preferred embodiment of the first aspect of the present invention, the compound is defined by formula III:

III

O R

'R

1 wherein RI and R 2 are alkyl;

R

3 is hydrogen, bromo, chloro or fluoro;

R

5 is halogen; S, R6 is halogen or nitro;

R

7 is a member as defined in Claim 1 or

R

P and R7 are combined through an -OCH,(C=O)-N- (propynyl)-linkage to form a fused six membered ring.

3- More preferably, in said compounds of formula III, Rand R 2 are methyl; R 3 is hydrogen, bromo or chioro; R 5 is chloro or fluoro; R 6 is chloro, fluoro or nitro; R 7 is a YR 11 member as defined in Formula II, or

R

6 and R 7 are combined through an -OCH 2 (propynyl)-linkage to give a fused 6 membered ring.

Still more preferably, the compounds of the present invention are selected from the group consisting of 4-Chloro-3- (2-f luoro-4-chloro-5- (-2-propynyloxy) phenyl) -lH-pyrazole 4-Bromo-3-(2-fluoro-4--chloro-5- (2-propynyloxy)phenyl) (methylsulfonyl) -lH-pyrazole 4-Chloro-3-(2-f luoro-4--chloro-5- (2-methoxyethoxy) phenyl) (methylsulfonyl) -Jl-pyrazole 4-Broino-3- (2-fluoro-4-chloro-5-(2-methoxyethoxy)phenyl) (methylsulfonyl) -lH-pyrazole 6- (4-Chloro-l-inethyl-5- (methylsulfonyl) -lH-pyrazol-3-yl) -q fluoro-4-(2-propynyl)-2H-1,4-benzoxazin-3-(4H)one (5-(4-Bromo-l-methyl-5-(methylsulfonyl)-lH-pyrazol-3-yl)- 2-chloro-4-fluorophenoxy) acetic acid, 1-methylethyl ester (4-Chloro-l-methyl-5- (methylsulf onyl) -lH-pyrazol-3-yl) 2-chloro-4-fluorophenoxy) acetic acid, 1-methylethyl ester 2- (5-(4-Bromo-l-methyl-5- (methylsulfonyl) -lI--pyrazol-3-yl) 2-chloro-4-fluorophenoxy)propanoic acid, ethyl ester and 2- (4-Chloro-l-methyl-5- (methylsulf onyl) -lH-pyrazol-3yl) -2-chloro-4-fluorophenoxy)propanoic acid, ethyl ester.

3A Most preferably, the compounds of the present invention are: 4-Chloro-3- (2-f 1uoro-4-chloro-5-(2-propynyloxy) phenyl) -l-methyl-5- (methylsulf onyl) -1H-pyrazole or 4-Bromo-3- (2-f luoro-4-chloro-5-2-propynyloxy) phenyl) -l-methyl-5- (methylsulf onyl) -lH-pyrazole or 2- (4-Chloro-l-methyl-5- (methylsulf onyl) -lHpyrazol-3-yl) -2-chloro--4-fluorophenoxy)propanoic acid, ethyl ester; or 4 -Chloro-l-methyl-5-(methylsulfonyl).1Hpyrazol-3-yl) -2-chloro-4-fluorophenoxy) acetic acid, 1methylethyl ester.

In a pref erred embodiment of the second aspect of the present invention, the process is characterized in that in said compounds according to Formula II,

R

1 1 R 2 and R, are as defined in Formula II;

R

5 is independently one of said R 3 members and

R

6 and R7are members as defined in Formula II or are combined to form a heterocyclic ring having up to 9 members and containing 0, N and/or S atoms, which ring may I *g be substituted with alkyl, haloalkyl, alkoxy, alkenyl or alkynyl radicals each having up to 4 carbon atoms; provided that when said two R6~ and R, members are combined through a -hetero, atom linkage, said heterocyclic ring has at least six ring members.

3B In a further preferred embodiment of the second aspect of the present invention, the process is characterized in that said compounds according to Formula II are those as defined for Formula III R N (SO-Rz

RI

wherein R, and R 2 and are C, 5 alkyl; R3 and R, are hydrogen, bromo, chloro or fluoro; RI is an R 5 member or nitro;

R

7 is a member as defined in formula II or R and R, are combined through an -OCHC 2 linkage to form a fused six-membered ring. More preferably, RI and R 2 and methyl;

R

3 is hydrogen, bromo or chloro; is chloro or fluoro; PR is chloro, fluoro or nitro and

R

7 is a YRI, member as defined in formula II.

In a still further preferred embodiment of the second i aspect of the present invention, the process is characterized 3C in reacting a Formula II compound wherein R 3 is hydrogen, with a halogenating agent; more preferably said Formula II compounds prepared by the halogenation process are those as defined for Formula III wherein R 3 is halogen; still more preferably wherein R1 and R are methyl, Rg is chloro or fluoro and R6 is chloro, fluoro or nitro.

In a still further preferred embodiment of the second aspect of the present invention, the process is characterized in that in the compound of formula II one of said R 7 members is -YR 11 and R 11 is not hydrogen, which process comprises reacting the corresponding compound of Formula II wherein R 11 is hydrogen with an acylating or alkylating agent; more preferably wherein said compound of Formula II prior to said acylation or alkylation is a compound as defined for Formula III wherein R7 is -YH.

ee e 4 Thus, the present relates generally to compounds of the formula 0 I N(RlN N Ri wherei:-

R

1 is hydrogen, C-.

5 alkyl optionally substituted with an R. member; C3.8 cycloalkyl or cycloalkenyl optionally substituted with C.i. alkyl;

R

2 is C 1 5 alkyl optionally substituted with an R, member;

R

3 is hydrogen or halogen and R. is hydrogen, C.,g alkyl, halcalkyl, alkylthio, alkoxyalkyl or polyalkoxyalkyl, C 3 8 cycloalkyl, cycloalkenyl, cycloalkyalkyl or cycloalkenylalkyl;

C

2 alkenyl or alkynyl. carbamyl, halogen, amino, nitro, cyano, hydroxy, heterocycle containing 1-4 0, S(O).

and/or N hetero atoms, C, 2 Z aryl, aralkyl or alkaryl, -CXYR, -CXR, -C -CH0OCOR, 1

-YR

11 -NR1~2 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, Swhich may be substituted with any of said R. members or where not self-inclusive said Re or R.s,3 members ee substituted with any of said R members; provided that when said two R, members are combined through a -hetero 0

II

atom linkage, said heterocyclic ring has at least six ring members; X is 0, NR1 or CR, 5

R,

6 Y is 0 or or NR 1 7;

RP-R

1 7 are one of said R 4 members; WO 92/02509 PCI'/US9 1/05530 4A xis 0-2 and n is A preferred subgenus of substituted-arylpyrazoly. compounds are those according to Formula 11

R-

6 Q R 3

N

N (SO) -R 2 wherein Rif R 2 F R 3 R 5 R 6 and R 7 are as defined above in relation to Formula II. Particularly preferred compounds of this invention are those according to Formula III 0) R 3 wherein Rl, R 2 f R 3

R

5 ,f R 6 and R7are as defined in relation to Formulp III.

S.

I

0

S

0 a

C

an

N

'V

Lu .0 o~' 5 Thus, an aspect of this inventior "elates to processes for preparing the compounds accc Ing to FormulaeII-III and their precursors and intermediates starting materials. These process aspects will be discussed in more detail below.

Other aspects of this invention relate to herbicidal compositions containing the compounds of FormulaeII-III and to herbicidal methods of using those compositi<ns to control undesirable weeds.

It is further within the purview of this inver.tion that the substituted-arylpyrazole compounds of Formulae -IIII 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, antidotes (safeners) for the herbicide(s), plant disease control agents, such as fungicides, insecticides, nematicides and other pesticides.

As used herein, the terms "alkyl", "alkenyi", alkynyl" when used either alone or in compound form, 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 1 to 4 carbon atoms, especially the halomethyl radicals, trifluoro- WO 92/02509 PCY/US91/055iO -6methyl. 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, decy'Lr, etc.; vinyl, allyl, crotyl, methiallyl, 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, methoxy, ethoxy, propoxys, butoxys, pentoxys and hexoxys and corresponding polyalkoxys and alkoxyalkyls, e.g., methoxymethoxy, methoxyethoxy, ethoxymethoxy, ethoxyethoxy, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, propoxymethyl, isopropoxymethyl, butoxymethyl, isobutoxymethyl, tertbutoxymethyl, pentoxymethyl, hexoxymethyl, etc., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, etc.; the isomeric cyclopentenes, cyclohexenes and cycloheptenes having mono-or di-unsaturation; representative aryl, aralkyl and alkaryl groups include phenyl, the isomeric tolyls and xylyls, benzyl, naphthyl, etc.

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

Representative heterocyclic members include: alkylthiodiazolyl; piperidyl; piperidylalkyl; dioxolanylalkyl, thiazolyl; alkylthiazolyl; benzothiazolyl; halobenzothiazolyl; furyl; alkyl-substituted furyl; furylalkyl; pyridyl; alkylpyridyl; alkyloxazolyl; tetrahydrofurylalkyl; 3-cyanothienyl; thienylalkyl; SUBSTITUTE SHEET WO 92/02509 PCrUS91/05530 -7alkyl-substituted thienyl; piperidinyl; alkylpiperidinyl; pyridyl; di- or tetrahydropyridinyl; alkyltetrahydromorpholyl; alkylmorpholyl; azabicyclononyl; diazacycloalkanyl, benzoalkylpyrrolidinyl; oxazolidinyl; perhydrooxazolidinyl; alkyloxazolidyl; furyloxazolidinyl, thienyloxazolidinyl, pyridyloxazolidinyl, pyrimidinyloxazolidinyl, benzooxazolidinyl, C 37 spirocycloalkyloxazolidinyl, alkylaminoalkenyl; alkylideneimino; 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.

SUBSTITUTE

SHEET

wo 92/02509 DoriT/ icni /nein1 .,v WA Q7f7" l IIA T-E07 A UJf DETAILED DESCRIPTION OF THEINVENTION The compounds according to this invention are suitably prepared by a variety of processes 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 pro 'cts of the above formulae. Viewed from this perspe,.ive, there are at least thirteen main process steps involved and these will be described below. The products according to Formulae I-Ill are prepared by the general "Processes I-XIII" scheme described below; it being expressly understood that various modification obvious to those skilled in the art are contemplated.

Specific embodiments are described in Examples 1-27 below.

In the sequence of process steps described below, the various symbols defining radical substituents, Ri-R^, 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 R 3 is H are prepared by this process step.

1) dithiokei R3 0 2) cyclizAtio. SR2 (R4) (R

R,

A

IF

SUBSTITUTE SHEET WO 92/02509 P(T/US91/05530 -9- The process for the preparation of compounds according to Formula B suitably proceeds from (un)substituted acetophenones of Formula A which are known in the art. The process can be carried out in any anhydrous solvent or mixture of such solvents; the preferred solvents are dimethylsulfoxide, toluene, benzene, etc.

The (un)substituted acetophenones are treated with a strong base such as an alkali hydride or alkali alkoxide with alkali alkoxides such as potassium t-butoxide being preferred. The basic mixture is treated with carbon disulfide. Reaction temperature is in the range of -100*C to 100*C, preferably -78C 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 temperature, 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 alkylhydrazines being preferred. Reaction temperature is in the range of -78C 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.

SUBSTITUTE

SHEET

WO 92/02509 PCUS91/05530 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 A. Buehler and D. E. Pearson, Survey of Organic Synthesis, pp. 285- 382, Wiley-Interscience, New York, 1970). Treatment of 2-chloro-4-fluoroanisole with titanium tetrachloride and dichloromethylmethylether at room temperature gives 2- The 2-fluoro- 4-chloro-5-methoxybenzaldehyde is converted to 2-fluoroby treatment with methyl Grignard followed by oxidation using standard methods known in the art.

The above mentioned 2-fluoro-4-chloro-5methoxyacetophenone and its analogous precursor, 2and processes for preparing them are the discovery of other inventors SUBSTITUTE

SHEET

WO 92/02509 PCT/US91/05530 -11- (Bruce C. Hamper arnd Kindrickc L. Leschinsky) employed by the assignee herein.

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

TABL I 3 PHSI LT&O Compound No.

physical dama rnp 0 C) or D(25 0

C)

CH

3

CH

3

CH

3 CH3

F

CH3

H

CF

3 6 CH 3 7

H

8 H 9 H

C(H)

I1I Et 12 CH 3

OCH

3 a

H

C3 a C2

F

H

F

OCH3 oCKH 3

OCH

3

H

fight yellow oil 90.0 4.0-45.0 50.0-5 nD 1.5533 (25 0

C)

nD 1.6036 (25 0

C)

90.0 88.0 133-135 66-67 nD 1.5989 (25 0

C)

iD 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 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 SUBSTITUTE ISHEET WO 92/02509 Vf-r/IICQ IQLCI -12prepare novel compounds typified by those shown in Table

II.

ABLE 1i PHYSICAL DATA FOR 3-ARYL-4

CI

SCH

2

RE

Compound No. R 1 R5 R 6 R7 physical dam mp or nD(25 0

C)

14 CH 3 F H F nD 1.5791

CH

3 F NHI 2 F 123.0-124.0 16 CH 3 F NH 2

OCH

3 nD 1.6212 17 CH 3 F C F nD 1.5937 18 CH 3 F a OCHi 3 87.0-88.0 19 CH 3 F C1 CH 3 83.0

CH

3 F OCH3 H RD 1.5943 21 H F C OCH3 151.0-152.5 SUBSTraTUTE SH EET 1111-1 n-I /rk 'EA nr-rr" I Tto",.',nrrl ''=nl T &.I AI 7L~ -13- rqLLIUaYI/Uy3ju S2 oxidation S 54 (Rj

N

B

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 1504C, 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

I

SUBSTITUTE SHET WO 92/02509 Pf/US91/0550 -14as crystallization or solvent extraction. If necessary, the product is purified by standard methods.

PROCESS III In this process description, one class of products according to Formula D wherein R. is halogen is prepared by the halogenation of the corresponding Formula C compound wherein R 3 is hydrogen and p is 0 or 2.

H R3 hs(o)R2 haogenati o n

S(O),

(R N (R 1

N

C R 1 D R 1 c D 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 -100C 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.

SUBSTITUTE

SHEET

WOI 9/0n250

V

,vu u~"U7 -15- PCT/US91/0553 PROCESS IV This section describes a process for the preparation of compounds according to Formula I in which one of the R. residues is a nitro group (Formula E) starting with compounds according to Formula I.

R3 NO RA 3 (n S0 2

R

2 nitration $R3 S 2

O

R

2

R

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

PROCESS V In this process description, one class of products according to Formula G (one species of Formula II compounds) is prepared by displacement of the Z radical of the corresponding compound of Formula F, wherein Z is any suitable leaving group of the previously defined R 4 members.

0 SUBSTiTUTE SHEET WO 92/02509 pr-rlyicol mzve-i -16- Z R3 SO orfUrf~ R7 R5 R Z O 2 R Z _S 0 2

R

NO

2 ,N02

R,

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 In 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 -100"C to 150*C, 'preferably -100C 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, 'eaction temperature, etc. The product is isolated after completion of the reaction by filtration and/o 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 P. members is a nitro residue).

_R

3 S0R So Ju SUBSTITUTE

SHEZT

WO 92/02509 PCr/US91/05530 -17- 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 concentration of the reaction mixture. If necessary, the product is purified by standard methods such as extraction, crystallization, column chromatography, etc.

B. The amine radical of the product of step A can be converted to a variety of functional groups, 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 SUBSTITUTE

SHEET

WO 92/02509 PCrmsqi9/055 0 -18solvents such as anhydrous acetonitrile are preferred.

A solution or slurry of the product of step A is treated with copper salts including cupric ha: ies, cuprous halides, mixtures of cupric and cuprous halides or other copper salts and their mixtures and with an alkyl nitrite or other organic nitrites, such as t-butylnitrite. Reaction temperature is in the range of 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, Meerwein, etc., reactions which employ diazonium salts as intermediates.

PROCESS VII In this process description, compounds according to Formula I, wherein one of the R, members is YH, are prepared from compounds according to Formula I wherein one of the R4 members is YR,, and 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, BBr 3 AiC1 3 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 SUBSTITUTE S-HEET WO 92/02509 PrPr/1 IQU1 Iccln -19- a a ,L ,UJ..

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 R. members is YR1, and R 11 is not hydrogen, are prepared from compounds according to Formula I wherein one of the R 4 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, dimethvlformamide, 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 1500C. 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.

This process describes the preparation of compounds of Formula M (Formula II compounds wherein R 7 is YCH 2 .,(Rj 8 )nCOYR 20 from the corresponding compounds of Formula K. The radicals Ri 8 2 are as previously defined for the said N members.

'U

SUBSTTUTE SHEET WO 92/02509 PITI C0111 L~

,V

y RI Re S02R2 S0 2 2 O (RiR) YO R

R

YR

1 9 0 OH K L Rs R3

R

YR

0

M

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 YR,, 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 0'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 SUBSTITUTE SHEET WO 92/02509 PCTUS91/0530 -21by 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 sulfuric acid). The amide derivatives can be prepared by treating compound L with the desired amine either neat or in a suitable solvent. The esterification or amide-forming reactions can also be carried out in the presence of an inert solvent and a dehydrating agent.

Alternatively, the product of step A can be converted to an acid halide or anhydride and treated with an alcohol or amine. Preparation of the acid halide is carried out in the presence of a halogenating agent such as, but not limited to, thionyl chloride, phosporus pentachloride, oxalyl chloride, etc., with or without an inert solvent. Any inert solvent which does not interfere with the reaction may be employed. A catalytic amount of an amine base such as triethylamine, pyridine or dimethylformamide or the like may be added for the purpose of promoting this reaction. The reaction temperature is in the range of -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 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.

SUBSTITUTE

SHEET

WO 92/02509 PCr/US91/05530 -22- The acid halide is treated with an alcohol or amine to give a compound of Formula M. Any inert solvent may be employed and a catalytic amount of an amine base such as triethylamine, pyridine or dimethylformamide or the like may be added for the purpose of promoting this reaction. The reaction temperature is in the range of -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 X This process describes the preparation of compounds of Formulae 0, P, Q, R, S or T (Formula II compounds in which the R 7 substituent is alkyl, substituted alkyl, haloalkyl, carboxaldehyde, carboxylic acid or a carboxylic acid derivative such as the previously defined CXYR, or CXRq) from compounds of Formula N. The radicals R 2 z and R 22 are as previously defined for the R 4 members and X, and X 2 are halogens.

Process schematics are shown below.

SUBSTITUTE

SHEET

WO 92/02509 -3 PCr/US9 1/05530 halogenation

Q

R

6

R

3 S0 2

R

2 R s

N

H

0 SUBSTITUTE

SHEET

WO 92/02509 PCPr/US91/05530 -24- 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 agescs 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 X, by a suitable nucleophile. Formation of products of Formula P can be carried out by treatment of compounds of Formula 0 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 O'C to 150*C, preferably 10*C to 100'C. The reaction period SUBSTITUTE

SHEET

WO 92/02509 PCT/uS9i/f5t3fi may be chosen from the range of a few minutes to several weeks depending on the amounts of reagents, reaction temperature, etc. The product is isolated after completion of the reaction by filtration and/or concentration of the reaction mixture. If necessary, the product is purified by standard methods such as extraction, crystallization, column chromatography, etc.

Formation of products of Formula R can be carried out by acid hydrolysis of compounds of Formula Q. To effect acid hydrolysis, compounds of Formula Q are subjected to an excess of a mineral acid such as hydrochloric acid or sulfuric acid, with a large excess of sulfuric acid being preferred. Reaction temperature is in the range of 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 crystallization or solvent extraction. If necessary, the product(s) are purified by standard methods.

Compounds of Formula S are obtained by oxidation of Formula P 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 crys- SUBSTITUTE SHEET WO 92/02509 PCT/US91/05530 -26tallization 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 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 reaction product by evaporation or distillation. The resultant acid halide may be subjected to an amine or alcohol directly and purified by the usual means.

SUBSTITUTE

SHEET

WO 92/02509 ~rr~ rr r~~r r~ -27- tPI/US91/0U55 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 R 4 residues is a thiol group (Formula U) starting with compounds according to Formula I.

R3 SH R 3 S(R 0SO 2

A

-N N-- (Rj, N* N RI R, I C 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, alkylnitriles, mineral acids, etc. An excess of chlorosulfonic acid is preferred as both the reagent and solvent for the formation of chlorosulfonyl intermediates. The reaction temperature is in the range of 25"C to the boiling point of the solvent employed.

The reaction period may be chosen from the range of a SUBSTITUTE SHEET WO 92/02509 -28- PCT/US91/05530 few minutes to several weeks depending on the amounts of reagents, reaction temperature, etc. After completion of the reaction the product or products are isolated by diluting the reaction mixture with water and the product(s) are isolated by a method such as crystallization or solvent extraction. If necessary, the product(s) are purified by standard methods.

Reduction of the halosulfonyl intermediate can be carried out in inert solvents including either organic or inorganic acids, such as acetic acid or hydrochloric acid, and may be used as concentrated acid solutions or dilute aqueous solutions. Reducing agents suitable in an acidic medium include, but are not limited to, metals such as iron, zinc or tin. The reaction solvent can include Reaction temperature is in the range of 0"C to 150C, 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 .ter and the product is isolated by a method such as crystallization or solvent extraction. If necessary, the product is purified by standard methods.

PROCESS XII In this process step, compounds of Formula V (Formula I compounds in which R, is CH 2

R

23 where R. is one of the previously defined R 4 members) are prepared from compounds of Formula I where R 2 is methyl.

O 3 O

R

3 CH, R O0 CH 2

R

1

R

V

SUBSTITUTE SHEET WO 92/02509 -29- PCT/US91/05530 Any suitable solvent may be employed provided that it is anhydrous, does not react with water, and does not interfere with the course of the reaction.

Preferably, anhydrous ethers such as tetrahydrofuran, diethyl ether or polyethers are employed. The reaction temperature is usually -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.

PROCESS XIII This process step describes the conversion of compounds of Formula W to either compounds of Formulae X or Y. The radical R 24 is as previously defined for one of the R. members and n is an integer of 0 or I.

Hso R5R X 0 2 N OR N N R

Y

SUBSTITUTE SHEET WO 92/02509 PC/US91/0530 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 R 24 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.

Alternatively, compounds of Formula W may be reduced by catalytic hydrogenation. For catalytic hydrogenation, which may be carried out at normal or elevated pressures, suitable catalysts include Raney nickel, palladium-carbon, palladium black, palladium on any suitable support, palladium oxide, platinum, platinu- 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.

SUBSTITUTE

SHEET

WO92/O25f19 Dr'r1 IT TC'Nt IA A WO 92/0l2509ff' TTA ilft -3 1- r I/ VOY t I 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.

ExamliP~l& All equipment was flame dried under N 2 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) fluoroacetophenone (commercially available) over 10 min.

A gas evolution was noted. The reaction was cooled to and 5.4 mL (0.09 mole) CS 2 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 CS 2 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 of 1-(2,5difluorophenyl)-3,3-bis(methylthio)-2-propen-l-one as a yellow solid, mp 105.50C; Alternatively, for the procedure described in step a mixture of anhydrous solvents can also be used, a mixture of DMSO and THF.

Anal. Calc. for C 11

H

1

F

2

OS

2 C,50.75; H,3.87; S,24.63.

Found: C,50.85; H,3.86; S,24.75.

To a slurry of 4.0 g (0.0154 mole) of the product of step in 50 mL acetonitrile was added 1.65 mL (0.031 mole) methylhydrazine over 15 min. at 240C. The solution was refluxed for 6 hr. The solution was stripped in vacuo. The residue was purified chromato- _1U SUBSTITUTE SHEET WO 92/02509 r\rmr mn rrrr-rn -32- rIUYII graphically using 10% ethyl acetate in hexane as the eluent to give 3.05 g of 3-(2,5-difluorophenyl)- 1-methyl-5-(methylthio)-1H-pyrazole as a light yellow oil; Anal. Calc. for CIIH,F 2 2 Sl: 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 Thie example describes the preparation of an isomeric mixture of 3-(2,5-difluorophenyl) methylthio-1H-pyrazole and 5-(2,5-difluorophenyl)-1methyl-3-methylthio-1H-pyrazole.

A. To a solution of 5.2 g l-(2,5-difluorophenyl)-3,3bis(methylthio)-2-propen-1-one in 50 mL acetonitrile at 24'C u.s added 1.3 mL of anhydrous hydrazine over a period of 3 minutes. The reaction was heated to for 1 hour. The reaction was concentrated in vacuo.

The residue was taken up in diethyl ether and washed with water, dried over anhydrous MgSO 4 and concentrated in vacuo. The residue was recrystallized from hexane ,o give 4.14 g of 3-(2,5-difluorophenyl)-5-(methythio)-1H-pyrazole as a white solid, mp 88*C.

Anal. Calc. for ClHF 2

N

2

S

1 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

K

2 C0 3 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 ith brine, dried over anhydrous MgSO 4 and concentrated in vacuo. The residue was purified chromatographically using 10% ethyl acetate in hexane as the eluent to give 2.97 g of 3-(2,5-difluorophenyl)-l-methyl-5methylthio-H-pyrazole (analysis given in Example 1) and 0.35 g of 5-(2,5-difulorophenyl)-1-methyl-3-

JU

SUBSTITUTE SHEET WA 0" /IncnQ I'1 -33- PC1TUS91/0553 (methylthio)-lH-pyrazole as a light yellow oil, n 1.5731.

Anal. Calc. for C, 1

HIF

2

N

2

S

1 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 1'C. After the addition was complete, the reaction was stirred for 15 minutes at '0C, followed by the addition of methyl iodide (23.6g, 0.38 mol) never letting the solution temperature rise above 1C. The solution was stirred using no cooling until it reached 10'C, at which time the reaction solution was poured onto 1L of ice water. Two crops of a filterable yellow solid were collected to give a total yield of 48.1g (96% yield) of the dithioketal. The dithioketal (47g, 0.180 mol) was dissolved in acetonitrile (500 ml) and methyl hydrazine (21g, 0.45 mol) was added all in one portion. The solution was brought to reflux for 24 hours and then most of the acetonitrile was stripped off under vacuum. The remaining liquid was poured onto ice water and extracted into diethyl ether.

The organics were washed with brine three times and dried over anhydrous magnesium sulfate, and stripped of all volatiles to give 37.77g (87% yield) of 3-(2,4difluorophenyl)-l-methyl-5-(methylthio)-lH-pyrazole as an amber oil. 'HNMR (CDC13) ppm: 7.82 J=6.6, 1H), 6.78 2H), 6.55 J=3.6, 1H), 3.83 3H), 2.34 3H), I0 SUBSTiTUTE SHEET WO 92/02509 PCFUS91/0530 -34- Anal. Calc. for C 11

HFF

2 NS,: 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-difluorophenyl)-l-methyl-5-(methylsulfonyl)-lHpyrazole.

A solution of 2.66 g (0.011 mole) of the product of step Example 1, in 50 mL methylene chloride was cooled to A solution of 7.6 g (0.022 mole) 50-60% mchloro-perbenzoic acid in 100 mL methylene chloride was added to the reaction mixture and allowed to stir overnight at room temperature. The solution was washed with a saturated sodium bicarbonate solution containing 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 of 3-(2,5-difluorophenyl)-l-methyl-5-(methylsulfonyl)-1H-pyrazole as a white solid, mp 126-127"C; Anal. Calc. for C 11

H

1 0

F

2 0 2

S

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

To a solution of 1.12 g of 5-(4-chloro-2fluoro-5-methoxyphenyl)-3-(methylthio)-lH-pyrazole in a mixture of 30 mL of glacial acetic acid and 15 mL of ethanol was added 3.2 g of Oxones. 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 HC1 SUBSTITUTE

SHEET

WO 92102509 PCr/US91/05530 afforded a solid precipitate which was collected and washed with water to afford 0.60 g of 5-(4chloro-2-f luoro-5-methoxyphenyl) (methylsulf onyl) -lHpyrazole. An analytical sample was obtained by recrystallization from methanol/water to give a yellow, crystalline solid; mp 213-216 (dec.) Anal. Calc. for C 11

H

10

N

2 0 3 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.

Exa]M~le 6 This example describes the preparation of 4chloro-3- (2-f luoro-4-methoxyphenyl) -1-methyl-5- (methylsulfonyl) -iM-pyrazole.

To a 0*C solution of 4-chloro-3-(2-fluoro-4methoxyphenyl) -1-methyl-5- (methylthio) -lH-pyrazole 0.0122 mol) in methylene chloride (150 mL) was added m-chloroberizoic acid in small portions. The reaction was stirred for 20 hours at room temperature, then the organics were extracted twice with a 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 Anal. Caic. for C, 2

H,

2

FN

2 0 3

S

1 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 doscribes the preparation of 4chloro-3- 5-dif luorophenyl) -l-methyl-5- (methylsulfonyl) -lH-pyrazole.

At 25*C, 2.25 g (8.2 umole) 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 SUBSTIT UTE SHE!ET WO 92/02509 PC-r/US91/05530 -36period of 50 minutes. The reaction was allowed to stir for 45 minutes. The reaction solution was poured into 300 mL ice water, and extracted with diethyl ether. The ether was washed with a saturated sodium bicarbonate solution, dried over anhydrous MgSO., and concentrated in vacuo. The residue was purified chromatographically using 30% ethyl acetate in hexane as the eluent to give 1.35 g of 4-chloro-3-(2,5-difluorophenyl) 1-methyl- 5-(methylsulfonyi)1H-pyrazole as a white solid, mp 770C; Anal. Caic. for C, 1

H

9 C1 1

F

2

N

2 0 2 C,43.08; H,2.96; N,9.13; S,10..45; C1,ll.56.

Found: C,43. 16;H, 2.97 12; This example describes the preparation of 4chloro-3- (2-f luoro-4-methoxyphenyl) -l-methyl-5- (methylthio) -1H-pyrazole.

To a 0*C solution of 3-(2-fluoro-4-methoxyphenyl) -1-methyl-5-(methylthio)-lH-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 77 g, 0. 009 mol) The reaction was stirred for one hour at room temperature and then poured onto ice. The organics were extracted~ into diethyl ether, washed with brine, dried over anhydrous magnesium sulfate and stripped In vacuo to give a yellow oil, 1.5943 at 250C.

Anal. Caic. for C, 2 H 2 F N 2 O1S 1 C1 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.

This example describes the preparation of 4chloro-3- (2 r5-dif luoro-4-nitrophenyl) (methylsulfonyl) -lH-pyrazole.

SUBSTra UTE SHEET WO 92/02509 PCr/US91/05530 -37- At 2C*C, 1.5 q (4.9 umole) 4-chloro-3-(2,5difluoropheiyl) -A-methyl-5-(methylsulfonyl) -lH-pyrazole, was slowly added to 25 mL of fuming nitric acid. The reaction was stirred at 300C for 30 minutes. The reaction was poured into 300 mL of ice. The slurry was filtered and the cake washed veil with water and air dried. The solid was recrystallized from methylcyclohexane to give 1.13 g of 4-chloro-3-(2,5-difluoro- 4-nitrophenyl) -1-methyl-5- (methylsulf onyl) -lH-pyrazole as a beige solid, up 147*C; Anal. Caic. for C 11 HsC1 1

F

2

N

3 0,S 1 C,37.56; H,2.29; N,11.95; S,9.12.

Found: C,37.60; H,2.29;N,li.98; S,9. Eape1 This example describes the preparation of 4chloro-3- (4-chloro-2-f luoro-5-nitrophenyl) (methylsulfonyl) -1H-pyrazole.

To a solution of 3g (0.0093 mol) of 4-chloro- 3- (4-chloro-2-f luorophenyl) -1-methyl-5- (methylsulf onyl) 1H-pyrazole in 3 mL of concentrated sulfuric acid was added a mixture of I mL of concentrated nitric acid in 3 mL concentrated sulfuric acid, dropwise. This mixture was then stirred at 250C for 2 hours. The reaction mixture was then poured into ice-water and extracted with ether. The organic extracts were then washed three times with 100 uL of aqueous NaCi, dried (MgSO, 4 filtered and concentrated to afford 2.3g of 4chloro-3- (4-chloro-2-f luoro-5-nitrophenyl) (methylsulfonyl)-lH-pyrazole as a yellow solid.

Chromatography (10% EtoAc/CH2C1 2 afforded an analytical, sample, up 111-115*C.

Anal. Calc. for C 11

H

8

N

3 0 4 C1FS, 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.

SUBSTITUTE C-HFET WO 92/02509 PC]r/US91/05530 -38- This example describes the preparation of 4chloro-3- (2-f luoro-5-methoxy-4-nitrophenyl) (methylsulfonyl) -1H-pyrazole.

A mixture of 4.8 g (0.0137 mole) of the product of Example 9, 1.9 g 014 mole) K 2 C0 3 and 5 mL methanol was slurried in 50 ML DMSO at 256C. The reaction was stirred at 450C for 8 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 MgSO 4 and stripped in vacuo. The residue was recrystallized from ethyl acetate/hexane to give 4.21 g of 4-chloro-3-(2-fluoro-5-methoxy-4-nitrophenyl)l-methyl-5-(methylsulfonyl)-lH-pyrazole as a yellow solid, mp 178.5-180*C; Anal. Caic. for Cj2? 11 C1 1

FN

3 0 5

S

1 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.

Aam12a This example describes the preparation of -1H-pyrazol-3-yl) 4-f luoro-N- (1-methylethyl) -2-nitrobenzenamine.

To a solution of 4-chloro-3-(2,5-difluoro-4nitrophenyl) -1-methyl-5- (methylsulfanyl) -lH-pyrazole (7.6g, 0.0218 mol) in n-methyl pyrrolidinone (50 al) was added isopropyl amine (1.94g, 0.0328 mol) potassium carbonate (4.5g, 0.0328 mol) and a catalytic amount of copper (II) fluoride. The reaction was heated to 600C for two hours and determined complete by TLC. The reaction was diluted into ethyl acetate and the organics were washed three times with brine, dried over anhydrous magnesium sulfate and the volatiles rem~oved under vacuum to give 8.4g of 5-[4-chloro-1-methyl-5-(methylsulf onyl) -lH-pyrazol-3-ylJ -4-f luoro-li- (1-methylethyl) 2-nitrobenzenamine as an orange solid after recrystalization from ethanol/methyl cyclohexane, mp 152*C.

SUBSTITIUTE SHEET WO 92/02509 WO 9202509PCT/US9I /05530 -39- Anal. Cale. for C 14

H

16 C1 1

F

1

H

4 0 4 C,43.03; H,4.13; N,14.34.

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

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

A slurry of 3.3 g (9.1 inmole) of 4-chloro-3-(2fluoro-5-methoxy-4-nitrophenyl) -1-methyl-5- (methylsulfonyl)-lH-pyrazole in 100 mL of acetic acid was heated to 800C under nitrogen and treated portionwise with 1.5 g (27 mmole) of iron powder. After 20 minutes at 850C, the mixture was allowed to cool and filtered through CeliteO. The resultant solution was diluted with 250 uL of water and extracted three times with ethyl acetate. The organic extracts were washed with water, saturated al. NaHCO 3 water, dried with HgSO4 and concentrated to afford 3.1 g of a tan solid.

A solution of 3.0 g (9.0 minole) of the product of step in 70 mt dry acetonitrile at 25*C was treated with 0.9 g (9.0 mmole) CuCl and 1.8 g (13.1 mmole) CuC 2 A solution of 2.4 mL (18 mmole) 90% t-butyl nitrite was added to the reaction mixture over 5 minutes. After 1 hour at 28-C the reaction mixture was concentrated in vacuc. The reaction residue was taken up in ethyl acetate and washed three times with a 10% HC1 solution, two times with brine, dried over anhydrous MgSO4. and concentrated In vacuo. The residue was purified chromatographically using 50% ethyl acetate in hexane as the eluent to give 2.64 g cof 4-chloro-3-(4-chloro- 2-f luoro-5-zethoxyphenyl) -l-methyl-5- (methylsulfonyl) 1H-pyrazole as a white solid, up 127.5*C.

Anal. Cale. for C 2

H

1 C1 2 FNZ0 3

S

1 C,40.81; H,3.14; N,7.93; S,9.08; C1,10.08.

Found: C,40.94; H,3.14; N,7.88; S,8.97; C1,19.95.

Examples 14-16 describe specific "Working embodiments of Process V1I.

SUBSTITUTE ISHEET WO 92/02509 PCFUS9VO55303 This example descrits the preparation of 2chloro-5-14-chloro-l-methyl-5-(methylsulfonyl)-1Hpyrazol-3-yl)-4-fluoro-$N-2-propenylbenzenamine A solution of 1 g (0.0023 mol) of N-[2-chloro- 4-chloro-1-methyl-5- (methylsulfonyl)-H-pyrazol-3yl)-4-fluorophenyl)-22,2-trifluoroacetamide, 0.97 g (0.007 mol) of potassium carbonate, 25 zL of anhydrous DMF and 0.85g (0.007 mol) of allyl bromide was allowed to stir at 70C for 24 hours. This solution was diluted with EtOAc, washed with three times 100 mL of 5% HC1, dried (MgSO.), filtered and concentrated to afford 0.9g of a red oil. This oil was dissolved in 20 mL of methanol and 3 uL of 10% NaOH was added. This mixture was stirred at 250C for 8 hours. The reaction mixture was diluted with EtOAc, washed with three times 100 mL of aqueous NaCi, dried (MgSO), filtered and concentrated to afford O.8g of a red oil. Chromatography (CH 2 Cl 2 afforded 0.6g of 2-chloro-5-(4-chloro--methyl-5- (methylsulfonyl)-lH-pyrazol-3-yl)-4-fluoro-N-2-propenylbenzenamine as a yellow oil, 1.5956.

Anal. Calc. for C 14

H

1

H

4

N

3 0 2 C1 2

F

1 5 1 C,44.46; H,3.73; N,11.11.

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

This example describes the preparation of N- [2-chloro-5-[14-chloro-l-methyl-5-(methylsulfonyl)-1Hpyrazol-3-yl]-4-f luorophenyl-methanesulfonamide.

To a solution of 0.5g (0.001 aol) of N-[2chloro-5-[4-chloro-1-methyl-5-(methylsulfonyl) -lpyrazol-3-ylJ-4-fluorophenyl]-N-(methylsulfonyl)methanesulfonamide in 20 mL of methanol was added 2 mL.

of 10% NaOH. This mixture was stirred at 250C for 4 hours. The reaction mixture was diluted with EtOAc, washed with three times 100 aL of 5% HCl, dried (MgSO.), filtered and concentrated to afford 0.2g of N-(2chloro-5-[4-chloro-l-methyl-5-(methylsulfonyl)-lHpyrazol-3-yl]-4-fluorophenyllmethanesulfonamide as a SUBSTITUTE SHEET WO 92/02509 PCT/US91/05530 -41yellow-tan solid. Chromatography (EtOAc) afforded an analytical sample, mp 165-166*C.

Anal. Calc. for C 12

H

2

N

3 0 4 C1 2

FS

2 1/4 EtOAc: C,35.18; H,3.24; N,9.65.

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

Emee 16 This example describes the preparation of 4chloro-3-(4-chloro-2-fluoro-5-hydroxyphenyl)-1-methyl- A solution of 1.15 g (3.25 mmole) 4-chloro-3- (4-chloro-2-fluoro-5-methoxyphenyl)-l-methyl-5-(methylsulfonyl)-1H-pyrazole in 30 mL methylene chloride was chilled to O'C and treated with 4 mL of a IM methylene chloride solution of BBr 3 (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 MgSo0, and concentrated in vacuo. The residue was recrystallized from hexane to give 1.1 g (100%) of 4-chloro-3-(4chloro-2-fluoro-5-hydroxyphenyl)-l-methyl-5-(methylsulfonyl)-1H-pyrazole as a beige solid, mp 190.5C; Anal. Calc. for C 11 HgC1 2

F,N

2 0 3 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.

Examle 17 This example describes the preparation of 2chloro-5-[4-chloro-l-methyl-5-(methylsulfonyl)-lHpyrazol-3-yl]-4-f luoro-N-(1-methylethyl)-benzeneasine.

A solution of 0.5g (0.0015 mol) of 2-chloro- 5-[4-chloro-1-methyl-5-(methylsulfonyl)-lH-pyrazol-3yl]-4-fluorobenzenamine and 2 mL of 2-iodopropane in mL of anhydrous DMF was stirred at 756C 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 HC1, dried (MgSO4), filtered and concentrated to afford red oil. Chromatography (methylene chloride) afforded 0.25g of 2-chloro-5-[4-chloro-l-methyl SUBSTITUTE

SHEET

WO 92/02509 PCF/US91/05530 -42- -lH-pyraZol-3-yl)-4-fluoro-N-(lmethylethyl)-benzeneamine as a red solid, mp 1189c- 121*C.

Anal. Caic. for C 14

H

15

N

3 0 2 C1 2

F

1 S, 1/2 H 2 0: C,43.20; H,4.40; N,10.79.

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

This example describes the preparation of N- 4-chloro-l-methyl-5- (methylsulfonyl) -iRpyrazol-3-yl)-4-fluorophenyl)-alanine, ethyl ester.

A solution of alanine, N-[2-chloro-5-(4- (methylsulfonyl) -lH-pyrazol-3-yl) -4fluorophenyll- in ethanol with a catalytic amount of acetyl chloride was allowed to stir at 250C for 18 hours. This solution was diluted with EtOAc, washed with water, two times with 100 m.L of aqueous potassium carbonate, dried (MgS0O), filtered and concentrated to afford 0.5g of a yellow oil. Chromatography (CH 2 Cl 2 afforded 0.17g of N-(2-chloro-5-[4-chloro-liethyl-5- (methylsulf onyl) -lIH-pyirazol-3 -y1) -4 -tluorophenyl]-alanine, ethyl ester as a yellow oil. 'HN)MR (400 M'Hz, CDCl 3 d 1.2 3H), 1.48 3H), 3.23 3H), 3. 8 1H) 4. 15 2H) 4. 18 3H) 4. 7 (bs, 1H) 6.6 1H), 7.1 1H) ppm: 9FNI(36Isffz, C~D 3 d 128 1F) ppm.

Anal. Cab,. for C 16

H

18

N

3 0,Cl 2

F

1 C,43.85; H,4.14; N,9.59.

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

This example describes the preparation of N- (2-chloro-5-[4-chloro-1-methyl-5-(uethylsulfonyl) -liipyrazol-3-yl] -4-f luorophenyl) (methylsulf onyl) methane--' sulfonamide.

To a solution of 0.5g (0.0015 mol) of 2- (4-chloro-2.-methyl-5- (methylsulfonyl) -lHpyrazol-3-yl]-4-fluorobenzeneamine in 20 mL of methylene chlor&de was added 0.33g (0.0033 mob) of triethylanine followed by 0.37g (0.0033 mol) of methanesulfonyl chloride. This mixture was stirred at 25*C for 180 SUBSTITUTE SHEET WO 92/02509 PCr/US91/05530 -43hours. The reaction mixture was diluted with EtOAc, washed with three times 100 aL of 5% Hli, dried (MgSO,), filtered and concentrated to afford 0.7g of N-[2chloro-5-[4-chloro-l-methyl-5-(methylsufonyl) -lHpyrazol-3-yl)-4-fluorophenyl]-N-(methylsulfonyl)methanesulfonamide as an off-white solid. Chromatography (EtOAc) afforded an analytical sample, mp 234- 2370C.

Anal. Cale. for C 13

H,,N

3 0 6 C1 2

F

1

S

3 1/4 EtOAc: C,32.17; H,3.14; N,8.18.

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

znmrsle. 29 This example describes the preparation of 4-ch.oro-3-(4-chloro-2-fluoro-5- (2-propynyloxy)- A mixture of 0.87 g (2.5 mmole) of 4-chioro- 3-(4-chloro-2-fluoro-5-hydroxyphenyl)-i-methyl-5- (methylsulfonyl)-1H-pyrazole, 0.4 g (3.0 mmole) K 2 C0 3 and 0.3 mL (3.0 mmole) propargyl bromide were slurried in 10 mL DMSO at 25*C. The reaction was stirred at 450C for 16 hours. The reaction was cooled, diluted with 100 mL cold water, and extracted four times with ethyl acmtate. The ethyl acetate extracts were washed with brine, dried over anhydrous MgSO 4 and stripped in vacuo.

The residue was purified chromatogjraphically using ethyl acetate in hexane as the eluent to give 0.93 g of 4-chloro-3-(4-chloro-2-fluoro-5-(2propynyloxy) phenyl) -1-methyl-5- imethylsulf onyl) -ilpyrazole as a tan solid, mp 1359C. Anal. Calc. for

C

14

H

1 C1 2

F

1

N

2 0 3 5 1 C44.58; 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.

xamle 21 This example describes the preparation of 2- (2-chloro-5-(4-chloro-1-methyl-5-(methylsuirnl)-lHpyrazol-3-yl)-4-fluorophenoxy)-propanoic acid.

SUBSTrIT UTE 8SHEET WO 92/02509 PCT/US91/05530 -44- To a slurry of 3.77 g (8.6 amole) 2-(2-chloro- 5-(4-chloro-l-methyl-5-(methylsulfonyl)-lH-pyrazol-3yl)-4-fluorophenoxy)-propanoic acid, ethyl ester in mL water and 20 mL 1,4-dioxane was added 3.5 mL (8.6 mmole) 10% aqueous NaOH. The reaction became clear after 30 min. and a TLC indicated that the reaction was complete. The solution was cooled and the pH adjusted to 3 with concentrated HCl. The reaction was extracted with ethyl acetate. The extracts were washed with water, dried over anhydrous MgSO 4 and concentrated in vacuo. The residue was recrystallized from hexane to give 2.9g 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 C,,H, 3 ClFN 2 OsS 1 C,40.80; H,3.19; N,6.81.

Tri C,40.87; H,3.24; N,6.69.

Examle 22 This example describes the preparation of 2- (2-chloro-5-(4-chloro-l-methyl-5-(methylsulfonyl)- 1-pyrazol-3-yl)-4-fluorophenoxy)-N-methylpropanamide.

To a solution of 1.17g (5.9 mmole) 2-(2- (4-chloro-l-methyl-5- (uethylsulonyl) -1Hpyrazol-3-yl)-4-fluorophenoxy)-propanoic acid in 10 aL methylene chloride was added 0.8 mL (9.6 mmole) oxalyl chloride over 3 minutes, causing the evolution of gas.

When this evolution ceased, one drop of DMF was added and the solution stirred until the gas evolution ceased.

The solution was stripped to dryness in vacuo. The residue was dissolved in 5 mL THF and at 0OC added to mL of a 40% aqueous solution of methyl amine over minutes. The reaction mixture was allowed to stir for minutes at room temperature. The solution was poured into 150 mL cold water and extracted with ethyl acetate.

The ethyl acetate extracts were washed times with brine, dried over anhydrous MgSO 4 and stripped in vacuo. The solid wan recrystallized from methylcyclohexane/ethyl acetate to give 0.96g of 2-(2-chloro-5-(4-chloro- SUBSTITUTE

SHEET

WO 92/02509 PC'f/US91/05530 1-methYl-S-(ethylsulfonyl)-1H-pyrazol-3-y)-4-f luorophenoxy)-N-ukethylpropanamide as a white solid, up 178'C; I HNMR (CDC1 3 ppm: 1.55 3H), 2.81 3M), 3.23 (s, 3H), 4.17 3H), 4.64 3H), 6.65 (br, 1H), 6.97 (d, 1H), 7.22 IH).

Anal. Calc. for C 15

H

16 Cl 2

F

1

N

3 0S, 1 C,42.46; H,3.80; N,9.90.

Found: C,4260; H,3.68; N,9.86.

Examples 23 and 24 describe specific working embodiments of Process X.

=12 23 This example describes the preparation of (((2-chloro-5-(4-chlro--methyl-5-(methylsulfonyl) -ipyrazol-3-yl) -4-f luorophenyl)methyl)thio) acetic acid, ethyl ester.

At 250C, 1.25g (3.0 mmole) 4-chloro-2-fluorophenyl)-4-chloro-l-methyl-5-(methylsulfonyl)-lH-pyrazole, 0.5g (3.3 mmole) K 2 C0 3 and 0.4 mL (3.3 mmole) ethyl bromoacetate were slurried in 15 m.L' acetone. The reaction was stirred at 200C for 8 hours.

The reaction was poured into 150 uL water, filtered and air dired. The solid was recrystallized from methylcyclohexane to give 1.2g of (((2-chloro-5-(4chloro-l-methyl-5-(aethylsulfonyl)-lH-pyrazol-3-yl)-4fluorophenyl)uethyl)thio)acetic acid, ethyl ester as a white solid, up 1106C.

Anal. Cale. for C,,H 1

H

1 C1 2

FN

2 OS,: C,42.20; H,3.76; N1,6.15.

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

Um3Ple 24 This example describes the praiparation of 2chloro-5-(4-chlro-l-ehyl-5- (ethylsul~onyl) -lpyrazol-3-yl) -4fluoro-N-met.ylbenzamide.

To a solution of l.34g (3.7 mmole) 2-chloro- 5-(4-chloro-l-uethyl-5-(methylsulfonyl)-1H-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 DHF was added and the solution stirred until the gas evolution ceased. The SUBSTI'TUTE SHEET W92059-46- PCT/US91/05530 solution was stripped to dryness in vacua. The residue was dissolved in 5 mL THF and at 0OC added to 10 mL of a 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 fro~m methylcyclohexane/ethyl acetate to give 0.95g of 2-chloro-5-(4-chloro-1-methyl-5- (methylsulfonyl) -lH-pyrazol-3-yl) -4-f luoro-N-methylbenzamide as a white solid, mp 1874C.

Anal. Calc. for C 13

H

12 Cl 2

F

13 0 3 SI: C,41.07; H,3.18; N,11.05.

Found: C,41.12; H,3.13; H,11.03., This example describes the preparation of 2chloro-5--(4-chloro-1-methyl-5-(methylsulfonyl) -lHpyrazol-3-yl)-4-fluorobenzenethiol and is a specific working embodiment of Process XI.

A slurry of 9.3g (0.022 mole) 2-chloro-5-(4- (methylsulfonyl) -lH-pyrazol-3-yl) -4fluorobenzenesulfonyl chloride and 29g (0.44 mole) zinc powder in 125 mL glacial acetic acid was stirred at 900C for 4 hours. The slurry was cooled and filtered through Celitee. 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 of 2 -chloro-5- (4-chloio-1-methyl-5- (methylsulfonyl) -1Hpyrazol-3-yl)-4-fluorobenzenethiol as a white solid, mp Anal. Caic. for C, 1 HCl 2

F

1 No~S 2 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.

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

SUBS TITUTE SHEET WO Q7/fl7n 41"J PCT/US91/05530 All equipment was flame dried unaer nitrogen.

To a solution of 4-chloro-3-(4-chloro-2-fluoro-5- -H-pyrazole (1.25g, 3.5 mmol) in 50 ml dry tetrahydrofuran at -78*C was added a 1M solution of n-butyl lithium (3.5 wl, mmol) never letting the temperature rise above The reaction was stirred for 30 minutes at -78C 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 wit. 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 Anal. Calc. for C 1 3

H

1 3

N

2 0 3 SC1 2 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 7- (4-chloro-l-methyl-5-(methylsulfonyl)-lH-pyrazol-3-yl]- 6-fluoro-2H-1,4-benzothiazin-4(3H)-one and is a specific working embodiment of Process XIII.

A solution of ((5-(4-chloro-l-methyl-5- (methylsulfonyl)-lH-pyrazol-3-yl)-4-fluoro-2-nitrophenyl)thio)acetic acid, ethyl ester (3.0g, 6.6 mmol) in glacial acetic acid (150 ml) was heated to 80"C and iron 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 of the compound named in the first paragraph of this example as a white solid, mp 245'C; 'HNMR (CDC1 3 ppm: 7.28 J 7.2, 1H), 6.79 J 10.8, 1H), 4.1 3H), 3.27 2H), 3.22 3H).

Anal. Calc. for C 13 HCIFNz0 3 C,41.55; H,2.95; N,11.18.

Found: C,41.72; H,3.09; N,10.81.

SUBSTITUTE SHEET WO 92/02509 PCT/US91/05530 -48- Tables 3 and 4 show examples of compounds prepared by Procrsses II-XIII and/or any combination of these processes as exemplified in Examples 1-27.

SUBSTITIUTE SHEET Table 3. Phys*ca Dot forMeakhyi-3- Cmouupod No. R 3 Is R 6 R7physkaldate 22 Br F cl OCIIZCH20CII3 106.0 23 Br F cl OCII2CO2CH2CII3 115.0 24 al a cl Ii 117.0 a al a NH12 135.0 26 l al al N02 190.

27 im al N4S02CI13)2 >250 al A al MiISO2CI2C3 177.0 29 0 al al (SO2CH2CH3)2 213.0 as a al NIISO2CH3 176.0 31 aF al CI128r 141.04143.0 32 aF cl CI120C112C120C113 nD 1.5629 33 cl F cl C112001120113 76.0-77.0 En0 0 (ca a F 'M2"12.

36' a1 F al (32SC12C02C1201i3 110.0 37 a3 F a C113 141.0 31 a2 P a (31Br2 144.0-146.0

U'

p9 al F to0 150.0-152.0 C a0 C3 a CO212 3 117.0 41 03 P a C02CH2CO2QI2CII3 79.0 42 0 p al C0211 194.0-1960 43 (3 F a CONIICH3 137.0 44 al F a F 137.0 a F al 11 104.0-107.0 46 a F a N(OI12CO2CH2CH3K)CF3 146.0-149.0 47 a3 F al N(CH2OC)COCF3 149.0-151.0 48 C3 F a N(Cl13)2 116.0-122.0 49 a F a3 N(SO2CI13)2 234-237 s0 a F 0 4-moipholint 131.0 0

M

in 0% 00-0*6Z H3YmZ(IL)IL.X) L) 0 L9

U)

OILI IFHINOO(CID)10o D 4 .0 99 OE I (HJZooHtI~jN"EHZI)kc0 D aI 0S 099HZO3(CFI)IOO 0 a 0 OF9 6UKI a" 1CwJZw.IZ:(H:)IlOo D a 0 (9 0o9ri Z(H: 1 00) 0 a 0 Z 99K, I1 0u fzI(Z~~o 0) a 19 WaftI EHXOCFw))O-s? 0 a 0 09 %il-Ill roN 0 a 0 991-01 CIOZOSUN D d 0 I oEd*6I(OWH~N 0 a 0 L ~iIH3mZ t HZ)IIN 0 d 0 9 In I0*001-0'66 (ItOZOZIORN D d 0 f 9S69'1 (P CHZO-HJZriZJIIN 0 a 0 K A2A& fHI0ZHtZOZY(1O)1IIN D a cc lI-8ll X(E(H131N 0 a Z6 LCIiSI ZHN0A 0 "f joduLu( N o O in 42% 0 (130 L) A 33 0911I IH3 MZID D 0 to 0*6S 1Li Z([tD)HZSOZtO 0 d 33o P0! EZ(cJDowoazIoo 0 AI 0 0*801 £(F03OZIO D a 0 9 011 404OZO34o 0 d 33 FL 096 £,iJSZOJZH:jO 0 to D3 OL A69401 otljzztzuczlo D a 0 C9 IIt I(HZIZI3O 0) d 3 U9 OW (lsuozio 0pfq0

O

009Eozozo 0%V roiloD i 0VJ(6d CaniPoDW No. R 3 As R6aiR7aPh is 0F cl off 190.5 a6 F al SCH(C113)2 .o 87 a3 F (3 SC! l(C11 3 )C02C112C113 yellow oil Is aI F a SCll(Cl13)CO2CH3 yelloiel 29a F al SCH2CH-C112 94.0 Q IF 0l SCHi2cO2CII(C113)214.

91 a F 0l SCIIZCO2CII12CH3 95.0 92 a3 F a SCH2CwCH11.

93a F 0l SH 1111.0 94 0l IF al 0 2 C1(C13)2 136.0 a3 F Cl S001(C13)2 65.0 96 a F III F 77.0 97 a F N112 ocii2CJJ 94.0 98 a F N112 0C112(32F 139.0-190.0 0 F N112 0QI(C13)2 103.0 300 a F l2I~ 00-33 159.0 103 F N112 4- oipboine 1750

L

0 bJ MicIL (Cole) ul Cmrqoumd No. R] S R6 R7 phiic data aW 102a F F 147.0 103 a F N02 N(Ctl(C113)2)COCF3 145.0 104 a F N02 N(CI13)OC013 116.0 a F N02 4-mc pholine 175.0 106 a P 140 NHCI(C113)2 152.0 107 a F 107 (0012C 2)30CH3 aD 1.3507 IU' 108 0 F 142 OcWCIF3)2 157.0 109 a F N02 OCi2C1I2F 124.0-125.0 110 0 F N02 Clf12C1120C13 117.0-118.0 III a F N02 OCII7CII 2 SCII3 90.0 112 a F 142 0012013 155.0 113 0 F N02 C13 178.3-180.0 114 a F N402 SC(C13)2 164.0 115 a F N02 SCII(CH)CO2CH12C3 nD 1.5846 116 0 F 1402 SCIIZCO2CHzCt3 155.0 Ill c F O13 [1 75.0 III 0 F OC13 N01.0 0,

U'

ia (com't) M a No. R 3 RS R R physI data [IV cc 119 0 F of1 N02 130.0 (0 120 H F II F 126.0-127.0 w 121 H F 0l CH3 149.0 122 H F 0 1I 157.0- 159.0 123 H F 0 0013 169.0 124 Bf F N02 F 143.0 111 125 Br F N112 F 131.0 126 Br F N112 OC13 141.0 127 Br F HI F 97.0 123 Dr F 0 OC 130.0 129 Br F cI off 210.0 130 Br F 0 OCH2CWCH 130.0 131 r F OC12CO2CH(CH3)2 169.0 132 Dr F a 00i(013)C02CH2013 114.0 133 0 F a cis-OC(-CHCH3)C021 194.0 134 0 F 0 OCl(CHZO13)C02013 64.0 135 0 F 0 OC 2 CO IH 2 170.0 0 %0

CA

I

a

C,

u'

C,

0

LA

(A

0 WO 92/02509 WO 9202509PCT/US91/05530 -56-

U.

p.

o 00.0.0.02 o U. U. o U. a. 0I a. U. a

I

*1 SUBSTriTUTE

SHEET

0 T" a4. FhysicalDam for \0fnI~n~' Cpon NJo. Swmc Physical Data FH C HCX^ 144 107.0 N-N CO F CI 145 *0 12.012.

C~OCIAH

0S0 65.0 Tabl 4. Physical Doms for 3-Ml5A klofsylpjyramolms C=oued No. Smiceac Physical Data (op, C) 149 S165.0-166.0 *0' 150 1 213.0-216.0 151 NNN001910 152H usS

N

**CH.

0 (MP,0 129.0 133 5*0 00 33 028.0 154 0 F S *0219.0 94.0 156 CFA

'CH

S

0h TAks 4. PhydWa Dae foi cmapomd No. SobLUdw Physical Data (sp, *C) 137 S1196.0 0 0I

O

2

N

139 ot170.0 oN

UI

WO 92/02509 P(3r/US91/05530 -61- 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 compound; 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 wpeds 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: SUBSTITUTE

SHEET

WO 92/02509 PCF/US91/05530 -62- Yens- Yellow nutsedge Anbg Annual bluegrass Sejg Seedling johnsongrass Dobr Downy Brome Bygr Barnyardgrass moqi Morningglory Cobu Cocklebur Vele Velvetleaf inau Indian mustard wibw wild buckwheat Where n'oted in the tables below, the symbol represents 100% control and the symbol indicates that the species was planted, but no data obtained for one reason or another.

SUBST1-RTUTE OSHEET WO 92/02509 -63- ZIluI PREZZMRGNCE ITT I. PLMN INHIBITION y A s Da ~c v Iw aene 0 0 0O fi Cpd. Rat* n b j b g b I a b No. kg/ha a 9 g r r I.u e u w 22 1.12 80 C C C C C 70 C C C 23 1.12 30 20 803020 C 8090 90 C 24 11.21 70 C 90 70 C 90 70 C C C 11.21 0 8080 70 807030 C C 26 11.21 0 0 0 0 0 0 080o10 0 27 11.21 0 0 50 2020 30 409070 28 11.21 C C 70 80 C C C CC C 29 11.21 20 C 80 40 C C 0 C C 1.12 80 40 4010 80 C C C C C 31 11.21 40 10 70 0 C 80 80 80 80 32 11.21 C C C C C C C C C C 33 11.21 90 C 90 C C C 70 CC C 34 11.21 90 C 90 60 C C 70 CC C 11.21 90 C C 50 C C 60 CC C 36 11.21 30 30 60 C 9060 60 C C C 37 11.21 60 80 9030 C C C CC C 38 11.21 80 808050 C 90 70 90 C C 39 11.21 90 C 908 CC CC c C 1.12 70 C 70 40 80 C 60 C C 41 1.12 70 5030 1080 C 20 C C C 42 11.21 8060o908 Co C C C C C 43 1.12 70 C C 50 90 c C C C C PCT/US91/05530 SUBSTITUTE SHEET WO 92/02509 -64- TAALE A =eotInUed1 PP.ENERGINCE 33STS I ELMW INHIBITION Y A S D B 34 C V IW nl e o y a o a nl Cpd. Rate ni b j b 9 q b 1 m b No. kg/ha a 9 g r r I. u a u w 44 11.21 90 C C C C C 90 C C C 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 6020 C 40 206090 C 49 1.12 0 90 90 1090 9030 C C C so 11.21 2086070 6090 C 20 C90 C 51 11.21 50 C C8 so O oc 90 C C 52 1.12 10 C C 90 9080 60 C C C 53 1.12 0 10 0 9040 9050 C C 54 1.12 40 10 30 20 0 70 30 C 90 SE 1.12 10 0 0 20 20 C 90 90 C C 56 1.12~ 10 9080 60 7090 70 C C C 57 1.12 10 0 0 0 0 30 2070 8070 58 1.12 70 4070 10 C 90 C C C C 59 11.21 50 C C8 soC90 90 C C C 1.12 30 70 C90 80 6040 C 70 C 61 1.12 S0 90 60 50 90 C 40 C C C 62 1.12 0 C 80 70 80 90 C 80 C a0 63 1.12 4050O90 90 CO 80 C C C 64 1.12 30 20 3080 C 70 C90 C 1.12 40 80 7050 C C 60 C C C PCr/US9l/05530 SUBSTITUTE ISHEET WO 92/02509 -65- PCr/US91/05530 TABLE PREEMERCENCE JESTS PLANT ZNHIBITIOt! Y A S D B M C VI W 0 nl @0 y 0 0 a l n Cpd. Rat* n b j b g g b 1 m b No. kg/ha m g g r r I u u w 66 1.12 60 c 90 40 C C 70 C C C 67 1.12 0 c 70 80 C C 80 C C C 68 1.12 20 906020 90 9070 C C 69 1.12 60 c 90 50 90 C 30 C C C 1.12 30 C 90 40 C C 30 C C C 71 1.12 30 C 90 40 c 80 30 C C 72 1.12 60 20 60 2080 C C 9090 73 1.12 50 1060 30 5090 8080 9080 1.12 40 08010 20 9060 8090 74 1.12 70 20 70 0 80 C C C C C 1.12 50 0 70 2080 C40 C 90 C 76 1.12 60 2030 2070 C 90 90 90 77 1.12 20 0 20 2080 C 70 C 8080 78 1.12 60 C 905 Co C C C C C 79 1.12 90 C 70 20 90 C C C C C 1.12 60 10 702020 C6090 90 81 1.12 60 C c 90 c 908 Co C C 82 1.12 50 50 802090 C 90 C C 83 1.12 70 C C C C C 60 C C C 84 1.12 0 8070 8080 CS80 C C C 11.21 90 9090 90 9090 C C C C 86 1.12 0 20 302020 4020 4080 SUBSTITUTE SHEET PCr/US91/05530 WO 92/02509 -66- XMIL 5 1 contlnud1 PE EROENGS ISTS 3 PL&UTINIDITIO Y AS D BDMC V I1W flo o y o o a nl I Cpd. Rate n b j b g q b 1 a b No. kg/ha a g 9 r r 1 u s u w 87 1.12 070 80 8060 C 80 C C C 8e 1.12 2040 80 8060 C 80 C C C 89 1.12 0 20 4030 80 8080 C C C 1.12 0 0 0 20 30 6030 C C C 91 1.12 20 10 1050O70 6060 C C C 92 1.12 0 80 40 60 50 C 60 C C 93 11.21 0 10 0 10 5020 0 8080 94 11.21 60 C C 70 C 90 30 C C C 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 98 11.21 0 0 20 0 0 0 0 0 0 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 8060 2050O70 0 102 11.21 40 30 6030 8050 060 C 103 11.21 20 80 80 20 80 90 70 90 80 104 11.21 40 C 80 80 90 70 80 C C C 105 11.21 40 809070 90 8060 C C 106 11.21 0 6070 30 604070 C90 107 11.21 40 90 7060 C 70 C C 108 11.21 30 90 9070 80 9080 C C C SUBSTITlUTE 00-HEET WO 92/02509 PCT/US91/05530 -67- TAiLE 5 fcontinued) PREE KRGEHCT TSTS SPLMAN INHIBITIO Y A S D B M C V I W Cpd.

No.

109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 Rate kg/ha 11.21 11.21 11.21 11.21 1.12 11.21 11.21 11.21 11.21 11.21 11.21 11.21 11.21 11.21 11.21 11.21 11.21 11.21 11.21 1.12 11.21 a a 70 80 40 80 60 8 0 S4 90 70 E 80 0 0 0 0 40 50 0 30 80 80 40 c n.

C

0 0 0 0 c 20 6 7 0 0 7 j g C 6 90 8 70 7 C 7 90 S 0 2 90 f 80 90 0 S0 0 0 90 0 40 0 0 0 40 C C C 90 0 60 o b r 0 0 0 0 0 0 20 70 0 0 0 0 0 C 2 2C 7 9 y g r 90 8i 90 9 C 2 90 C 3 20 7

C

60 9 C I 0 0 60 0 0 0 90 70 3 80 C C 0 90 0 80 0 0

C

0 0

C

10 F0 0 c 0 0 0 7( 71 2 9 8 0 a b 1 u e 90 C 90 C C C 70 C 60 90 20 30 3 C C 60 C 90 C 0 80 0 30 S0 0 S0 20 0 10 0 40 80 0 20 90 0 0 70 0 20 C c C c 0 c C 0 C C c c c c

C

c ?o 20 20 30 C 0 1( 9( 4' 9 i b

C

c I S0 0 0 C 0 0 C C C C C C 1.12 40 C 80 80 90 C 60 C C C SUBSTITUTE

SHEET

WO 92/02509 -68- TABLE I Icontinue~d) PU1ENER2111C! TESTS PLANT INDIRITIO y A S DI Ca m vIw ane o y Co o e 1 Cpd. Rat* n b jb g q b 1 m b No. kg/ha s g g r r 1 u e u w 131 1.12 8020 80 2070 C30 C 90 C 132 1.12 0 30 80 C 80 80 30 C C C 133 1.12 10 20 90 40 10 8O 30 C 80 c 134 1.12 C C 90 90 C 90 C C C C 135 1.12 CiSl 1C s10 C 60 C C C 136 1.12 10 9090 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 8020 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 9070 600 80 20 C90 142 11.21 60 C 90 20 90 90 60 C C C 143 1.12 0 4020 10 202068030 8070 144 11.21 0 20 0 20 0 0 0 2020 145 11.21 0 10 10 20 30 20 30 30 20 146 11.21 60 C C C C80 30 C C C 147 11.21 60 C 90 70 C 80 20 C C 148 11.21 s0 C C C C 905 Co C C 149 11.21 0 0 0 0 0 5020 7060 150 11.21 0 0 0 0 0 0 0 0 0 0 151 11.21 30 9090 3090 C 80 C C C 152 11.21 0 0 0 0 0 0 0 0 0 0 PC/US91/05530 SUBSTITUTE SHEET WO 92/02509 -9 -69- PCTr/US9I /05530 cpd. Rate No. kg/ha 153 1.21 3 154 1.12 7 155 1.12 f 156 1.12 157 1.12 158 1.12 159 11.21 *Wlbw-THIN.

Excesuive dam~ping off I observation ca. 4-weeks TABLE 5 (continuvol PREEMEEGENCE TEETS PLANT INHIBITIOIN Y A SODB M CV I1W a nl 0 y 00 oi aL n b j b g qb 1 mb a g g r r Iuea u w 10 60 C 70 90 80 40 C C C 0O C 80 80 90 C C C C C 30 C C 60 C C C C C C 0 C 90 30 90 90 90 C C 70 C 90 C C C C C C C 10 10 80 40 30 50 40 80 20 0 00 00 00 0 00 SUBSTIT UTE SHEET WO 92/02509 PerUS1/05530 POST-EMERGENCE HERBICIDE TESTS The post-emergence herbicidal activity of some of the various compounds of this invention was demonstrated by greenhouse testing in the following manner.

Topsoil is placed in aluminum pans having holes in the bottom and compacted to a depth of 0.95 to 1.27 cm from the top of the pan. A predetermined number of seeds of each of several dicotyledonous and ronocotyledonous 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 14 days (usually 11 days) and in some instances observed, again at 24-28 days (usually 25 days) after spraying.

The post-emergent herbicidal activity shown in Table 6 is the percent inhibition of each plant species.

SUBSTITUTE

SHEET

WO 92/02509 -71- %PLANT INHIBITION Y AS 0D BHC V I W a flU 0 y o a 0 nl j Cpd. Rate n b j b g g b 1 m b No. kg/ha a g g r r 1 u e u w 22 1.12 40 40 3050 30 C C C 8080 23 1.12 50 20 4040 80 C C C 60 C 24 11.21 40 60 80 30 90 80 70 C 90 C S 11.21 10 0 10 0 0 20 20 30 40 26 11.21 0 0 10 0 020 20 2030 0 27 11.21 0 0 0 0 103010 9050 28 11.21 20 10 10 0 10 80 C C 90 C 29 11.21 20 10 60 10 0 20 20 C 70 1.12 0 103020 30 9090 9080 31 11.21 0 20 20 0 20 8080 C 50 32 11.21 40 90 90 C 90 C 90 C 90 C 33 11.21 30 90 C C C 90 C C C C 34 11.21 20 40 70 10 70 80 80 C 90 11.21 30 10 70 0 C C 80 C 8070 36 0 11.21 2020 5030 40 6060 C 70 C 37 11.21 30 8090 90 C C C C C C 38 0 11.21 20 60 70 0 70 C 60 C 60 39 11.21 3080 80 2090 C 50 C90 1.12 40 90 90 C C 90 C C 90 41 1.12 10 1070 80 C C 60 C 90 42 11.21 60 9090 4080 C C C C C 43 1.12 20 0 4030 3090 90 C8SO70 Y?C7/US91/05530 SUBSTIT UTE SH-EET WO 92/02509 -72- TABLE 6 iggntinuodl POSTl-rmzRGENCE TEST PLANT IIWIBITION Y AS DOB M CVI iw aen. e y 0 o6 al n Cpd. Rate n b j b g g b I m b No. kg/ha x g g r r 1 u u w 44 11.21 40 C C C C C C C C C 11.21 30 P C 90 C c cc C Cc 46 1.12 20 0 0 0 0 3030 30 3060 47 1.12 20 0 20 20 0 30 305040 48 1.12 10 2020 2020 C 60 C40 49 8 1.12 0 10 0 0 0 40 30 50 40 11.21 20 30 90 50 50 70 60 90 C C 51 11.21 0 20 40 20 50 90 C C 80 C 52 1.12 2040 2020 40 9060 C 70 C 53 1.12 20 20 805090 90 C C 80 54 1.12 0 I0 40 20 10 30 40 70 60 1.12 30 10 40 20 80 C C C 7 0 c, 56 0 1.12 20 5020 20 0 90 90 C 70 57 1.12 0 0 0 0 0 2020 6050 58 0 1.12 20 10 20 0 30 C 90 C 70 C 59 11.21 2060 80 2080 C 9090 80 C 1.12 20 20 60 2060 C C C 50 61 1.12 30 60 90 C C 60 C C 8090 62 1.12 20 50 80 50 50 50 S0 90 70 63 1.12 3a 80 C C C C C 90 90 C 64 1.12 30 90 C C 90 C C C C C 1.12 30 60 80 9090 C C 90 C PCT/US9I /05530 SUBSTETUTE ESIF EE WO 92/02509 WO 9202509PCr/US9I/05530 -73- TABLE 6 V cgntinuedl POST-EMERGENCE TESTS PLANT INHIMITION Y A S D B M CV I W Cpd.

No.

66 67 68 69 71 72 73 74 76 77 78 79 81 82 83 84 86 Rat* kg/ha 1.12 1.12 1.12 1.12 1.12 1.12 1.12 1.12 1.12 1.12 1.12 1.12 1.12 1.12 1.12 1.12 1.12 1.12 1.12 11.21 1.12 0 9 1 90 5 60

C

90 so

C

c 90 s0 )90 3 60 0 b

U

'0 P0 so

C

Bo 90

C

80 90

C

c sc 9' 5' a n 1 m a u C 50 C C 90 60 4 C C 807 90 60 90 204 C C 60 C so 90 90 so 90 60 I90 90 80 c c C 90 90 C cso 0 90 C cso i b w

C

SUBSTITUTE SHEET WO092/02509 -74- PCT/US91 /05530 TABLE 6 (continued) POQST-EMERGENCZ TESTS PLANT INHIBITION Y A S D BMHC V I W n a 0 y o a n i.

Cpd. Rate n b j b g g b I m b No. kg/ha a g g r r 1 u a u w 87 1.12 10 40 80 C C C C C 90 88 1.12 20 70 80 C C CC C C 89 1.12 10 50 60 70 40 90 90 90 90 1.12 0 20 809090 9080C 80 91 1.12 10 4090 9090 80 C9090 92 1.12 40 70 7080 30 C C C 90 93 11.21 0 0 20 10 70 80 80 C 90 94 11.21 10 20 0 0 0 20 80 70 60 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 2030 6030 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 3010 101 11.21 0 0 20 0 0 30 2020 0 102 11.21 0 10 20 10 30 20 10 3.0 20 103 11.21 0 0 0 0 0 0 0 0 0 11.21 0 0 20 0 30 3050 50 3060 104 11.21 10 20 40 0 40 5060 8070 C 105 11.21 20 60 80 30 30 80 70 C 80 C 106 11.21 0 0 0 0 0 4040 5040 107 11.21 20 50 80 50 60 C C C C C SUBSTITUTE 18HE-ET WO 92/02509 PCT/US91/05530 -75- TABLE 6 fcontinuedl P $T-EMZERGENCE TESTS PLANT INHIBITION Y A S D B M C V I W a n o y o o a n i Cpd. Rate n b j b g g b i m b No. kg/ha a g g 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 80 112 11.21 20 60 90 40 50 40 70 C 80 C 113 1.12 0 0 10 0 10 10 10 20 0 114 11.21 0 0 0 0 0 0 30 20 0 115 11.21 30 30 C 90 90 90 C C C C 116 11.21 20 20 60 30 50 80 70 C 50 117 11.21 10 50 50 40 80 60 50 C 90 C 118 11.21 0 0 0 0 0 20 0 20 10 0 119 11.21 10 0 0 0 0 0 0 0 0 0 120 11.21 0 0 0 0 0 0 0 10 0 0 121 11.21 0 D 0 0 0 20 20 0 0 0 122 11.21 0 0 0 0 0 20 0 20 0 123 11.21 0 20 0 0 0 20 50 60 20 C 124 11.21 0 0 0 0 0 0 0 30 20 125 11.21 0 0 0 0 0 0 0 20 0 0 126 11.21 0 0 0 0 0 20 20 40 20 127 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 SUBSTTUTE SHEET WO 92/02509 PCT/US91/05530 -76- TABLE 6 (continued) POST-EMERGENCE TESTS PLANT INHIBITION Y A S D B M C V I W Cpd.

No.

130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 Rate kg/ha 1.12 1.12 1.12 1.12 1.12 1.12 1.12 11.21 11.21 11.21 11.21 1.12 11.21 1.12 11.21 11.21 11.21 11.21 11.21 11.21 11.21 n 30 6 40 2 30 3 10 4 0 S 20 10 20 0 10 20 0 10 20 0 10 10 0 10 0 0 j g 40 5 60 2 40 1 40 80 80 60

C

20 80 80 90 80 1 90 1 0 0 80 80 40 3 0 0 0 0 b r 0 20 80 30 c 0 30

C

0 30 10 80 20

C

20 0 9C 30 0 0 y g r 20 70 80 90 S

C

60 20 1

C

0 20 70 70 10 70 0 10 1 90 80 20 S0 0 0 0 1

C

C 9

C

90 s c

CE

80 C 40 50 60 80 40

C

20 20 60 80 20 10 20 n i m b u w C C 40 WrO 40 80 50 90 C C 20 C C C 70 70 30 90 20 40 S80 C 90 C 90 C 0 0 0 0 0 0 11.21 10 0 0 0 0 60 60 80 60 C SUBSTITUTE

SHEET

-77- WO 92/02509 Pcr/US91/05530 TABLE 6 (continuedi POST-EMERGENCE TESTS PLANT-INHIjITIO2N Y A S D B C V I W cpd.

No.

152 153 154 155 156 157 158 159 Rate kg/ha 11.21 11.21 1.12 1.12 1.12 1.12 1.12 11.21 Poor cocklebur response Duplicate test SUBSTIT UTE S1HEET WO 92/02509 PL-T/US91/05530 -78- 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 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 SUBSTITUTE

SHEET

WO 92/02509 PC'/US91/05530 -79- (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, Nmethylpyrrolidone, 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, with kerosene, to spray concentration.

SUBSTITUTE

SHEET

WO 92/02509 PCTr/US91/05530 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, finelydivided 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, SUBSTITUTE

SHEET

WO 92/02509 -81- WO 9202509-81-PCT/US91/05530 nitrophenyl ethers, diphenyl ethers, pyridines and the like suc-h as: HeteYclic Nitrogen/Sufur Derivatives 2-Chloro-4 -ethylamino-6-isopropylamino-.q-triazine 2-Chloro-4 ,6-bis (isopropylamino) -j-triazine 2-Chloro-4 ,6-bis (ethylamino) -j-triazine 3-Isopropyl-lH-2, 1,3-benzothiadiazin-4-(3H) -one 2,2dioxide 3-Amino-i, 2, 4-triazole 6,7-Dihydrodipyrido(l,2-:2',1'-c)-pyrazidiinium salt 5-Bromo-3 -isopropyl-6-methyluraci1 1, 1 -Dimethyl-4, 4 -bypyridinium 2- (4-Isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl) -3quinolinecarboxylic acid Isopropylamine salt of 2-(4-isopropyl-4-mothyl-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-methyl- 5-oxo-2-imidazolin-2-yl) -p-toluate 5- (Trifluoromethyl)-4-chloro-3-(3 '-(1-ethoxycarbonyl)ethoxy-4 '-nitrophenoxy) -1-methylpyrazol; (Trifluoromethyl) -4-chloro-3- (3 '-methoxy-4 '-nitrophenoxy) -1-methylpyrazole; (Tr if luoromethyl) -4 -chloro-3 -butoxycarbony 1)ethoxy-4 '-nitrophenoxy) -4-methylpyrazol; (Tnt luoromethyl) -4-chloro-3- (3 '-methyisulfamoylcarbonyl propoxy-4' -nitrophenoxy) -4-inethylpyrazol; (Trifluoromethyl) -4-chloro-3- (3 '-propoxycarbonylmethyloxime-4 '-nitrophenoxy) -1-methylpyrazole; (5-(Trifluoromethyl)-2-pyridinyl]oxy~phenoxy)propanoic acid (9C1).

S

1 S-dimethyl-2- (difluoromethyl) -4-isobutyl-6trifluoromethyl-3, 3-Pyridinecarboxylic Acid, 2-(difluoromethyl) dihydro-2-thiazolyl) -4-(2-methylpropyl) -6-(trifluoromethyl)-, methyl ester; acid, 2-(difluoromethyl) methylpropyl) (trifluoromethyl) dimethyl ester; SUBSTIT191UTE C-HEET WO 92/02509 PCr/US91/05530 -82- 3, 5-Pyridinedicarbothioic acid, 4-(cyclopropylmethyl) -2- (difluoromethyl) (trifluoromethyl) S, S-dimethyl ester; Sulfoximine, N- (diethoxyphosphinyl) -S-methyl-S-phenyl- N- (4-Chiorophenoxy) phenyl-N,N-dimethylurea NN-dimethyl-N (3-chloro-4-methylpheiyl) urea 3- 4-dichiorophenyl) 1-dimethylurea 1, 3-Dimethyl-3- (2-benzothiazolyl) urea 3- (p-Chlorophenyl) l-dimethylurea 1-Butyl-3- (3 ,4-dichlorophenyl) -1-methylurea 2-Chloro-N[ (4-methoxy-6-methyl-1, 3, 5-triazin-2-yl) aminocarbonyl J-benz enesulfonamide Methyl 6-dimethyl-2-pyrimidinyl)auino) carbonyl) amino) sulfonyl) benzoate Ethyl 1-Cmethyl ((4,6-dimethyl-2-pyrimidinyl) amino) carbonyl) amino) sulfonyl)] benzoate Methyl-2 ,6-dimethoxy pyrimidin-2-yl) aminocarbonyl)amino sulfonyl methyl) benzoate Methyl ((((4-methoxy-6-methyl-1,3,5-triazin-2-yl) amino) carbonyl) amino) sulfonyl) benzoate N-dimethylcarbamoyl) -2-pyridin-2-ylj sulfonyl- N' 6-diuethoxypyrimidin-2-yl)urea (3-ethylsulfonyl) -2-pyridin-2-yl)-sulfony.-N' dimethoxy-pyrimidin-2 -yl) urea N- (2-methoxycarbonyiphenyl sulfonyl) 6-bisdifluoromethoxypyrimidin-2 -yl) urea Amates /Thiolarbamates 2 -Chioroallyl diethyldithiocarbamate S- (4 -chlorobenzyl)N,N-diethylthiolcarbamate Isopropyl N- (3-chloroT~henyl) carbamate S-2, 3-dichioroallyl N, N-diisopropylthiolcarbamate S-N, N-dipropylthiolcarbamate S-propyl N, N-dipropylthiolcarbamate S-2,3, 3-trichloroallyl-N ,N-diisopropylthiolcarbamate SUBSTIT UTE S0-'HEET WO 92/02509 PCF/US91/05530 -83- Aceta ides /Acetani lides /Anil ines /&mides 2 -Chloro-N, N-diallylacetamide N, N-dimethyl-2,2-dipherlylacetamide N-(2,4-dimethylthiel-3-yl) -N-(l-methoxyprop-2-yl) -2chloroacetamide N- (lH-pyrazol-l-ylmethyl-N- 4-dimethylthiei-3-yl) -2chioroacetamide N-(l-pyrazol-l-ylmethyl) yl) -2-chioroacetamide N-(2,4-dimethyl-5-( (C(trifluoromethyl)suilfonyljamino)phenyl Jacetamide N-Isopropyl-2 -chioroacetanilide N-Isopropyl-l- 5-trimethylcyclohexen-l-yl) -2chioroacetamide 2' ,6 '-Diethyl-N-(butoxymethyl) -2-chioroacetanilide 2' ,.6'-Diethyl-N-(2-n-propoxyethyl) -2-chioroacetanilide 2' ,6 '-Dimethyl-N-(l-pyrazol-l-ylmethyl) -2-chioroa.-etanilide 2' ,6 '-Diethyl-N-methoxymethyl-2-chloroacetanilide 2 '-Methyl-6'-ethyl-N- (2-methoxyprop-2-yl) -2-chioroacetanilide 2 '-Methyl-6' tylN(ethoxymethyl) -2-chioroacetanilide aaa-Trifluoro-2 ,6-dinitro-N, N-dipropyl-p~-toluidine N- l-dime',.hylpropynyl) Acids/Esters IAlcohgog 2, 2-Dichioropropionic acid 2 -Methyl-4 -chlorophenoxyacetic acid 2, 4-Dichiorophenoxyacetic acid Methyl-2- (2,4-dichiorophenoxy) phenoxy) propionate 3-Amino-2, 5-dichlorobenzoic acid 2-Methoxy-3, 6-dichlorobenzoic acid 2,3, 6-Trichiorophenylacetic acid N- l-naphthylphthalamic acid Sodium 5-(2-chloro-4- (trifluoromethyl)phenoxy)-2nitrobenzoate 4, 6-Dinitro-o-sec-butylphenol N-(phosphonomethyl)glycine and its salts SUBSTITUTE SHEET W 92/02509 PCr/US91/05530 -84- Eutyl (5-(trifluoromethyl)-2-pyridinyl)oxy]phenoxy) propafloate 2, 4-Dichlorophenol-4-nitrophenyl ether 2-Chloro-6, 6, 8-trifluoro-p-tolyl-3-ethoxy-4-nitrodiphenyl ether (2-chloro-4-trifluoromethylphenoxy) -N-methylsulfonyl 2-nitrobenazmide 1 '-(Carboethoxy) ethyl 5-[2-chloro-4- (trifluoromethyl) phenoxy] -2-nitrobenzoate Miscellaneous 2, 6-Dichioroberizonitrile Monosodium acid methanearsonate Disodium methanearsonate 2-(2-chlorophenyl)methyl-4, 4-dimethyl-3-isoxazolidinone 7-Oxabicyclo heptane, l-methyl-4-(1-methylethyl) -2-(2-methylphenylmethoxy) exo- Glyphosate and salts thereof.

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

SUBSTITUTE SHEET WO 92/02509 PCT/US91/05530 Herbicidal formulations of the types described above are exemplified in several illustrative embodiments below.

I. Imusifiable -Concentrates We i A. Compound No. 22 Free acid of complex organic phosphate or aromatic or aliphatic hydrophobe base GAFAC RE-610, registered trademark of GAP Corp.', Polyoxyethylene/polyoxypropylene block copolymer with butanol 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 GAFAC RE-610) Polyoxyethylene/polyoxypropylene block copolymer with hutanol Tergitol Xli) Xylene Monochlorobenzene CT ht Percent 5.34 100.00 1.60 4.75 100.*00 100.00 C. Compound No. 43 Free acid of complex organic phosphate or aromatic or aliphatic hydrophobe base GAPAC RE-610, registered trademark of GAP Corp.) Polyoxyethylene/polyoxypropylene block copolymer with butanol Tergitol Xli, registere~d t~rademark of Union Carbide Corp.) Cyclohexanone Aromatic 200 SUBSTIT UTE SHEET WO 92/02509 PC'/US91/05530 -86- Weiqht Percent D. Compound of No. 52 Free acid of complex organic phosphate of aromatic or aliphatic hydrophobe base GAFAC RE-610 3.00 Polyoxyethylene/polyoxypropylene block copolymer with butanol Tergitol XH) Phenol Monochlorobenzene 85.0 100.00 E. Com.ound No. 53 1.50 Free acid of complex organic phosphate or aromatic or aliphatic hydrophobe base GAFAC RE-610, registered trademark of GAF Corp.) 4.50 Polyoxyethylene/polyoxypropylene block copolymer with butanol Tergitol XH, registered trademark of Union Carbide Corp.) 1.00 Isophorone 5.34 Emerset 2301 87.66 100.00 F. Compound No. 54 4.50 Free acid of complex organic phosphate of aromatic or aliphatic hydrophobe base GAFAC RE-610 3.00 Polyoxyethylene/polyoxypropylene block Scopolymer with butanol Tergitol XH) 2.00 Cyclohexanone 4.75 7-Butyrolactone 8575 100.00 SUBSTITUTE

SHEET

WO 92/02509 WO 9202509PCI'/US9I /05530 '-87- Weight Percent II, Flowables A. Compound No. 58 25.0 Xanthan Gum 0.3 Ethylene Glycol 10.0 sodium lignosulfonate Sodium N-methyl-N-oleyl taurate Water 6.

100.00 B. Compound No. 59 45.0 Xanthan Gum 0.2 Magnesium Aluminum Silicate 0.2 Alkyl aryl sulfonate Propylene glycol Water

A-

100.00 C. Compound No. 66 23.0 Xanthan gum 0.3 Propylene Glycol 10.0 Sodium lignosulfonate Alkyl aryl sulfonate Morwet D-425) Water&11 100.00 D. Compound No. 81 45.0 Magnesium Aluminum Silicate 0.3 Ethylene Glycol Alkyl. aryl sulfonate WO/PO Block Copolymer Pluronic P-1C4) Water A2II 100.00 SUBSTITUTE SHEET WO 92/02509 PCr/US91/05530 -88- Weight Percent Ill. Wettable P~owders A Compound No. 83 25.0 Sodium lignosulforiate Kaolin 60.0 Amorphous silica (synthetic) 1.

100.0 B. Compound No. 85 80.0 Sodium dioctyl sulfosuccinate1.

Alkyl Aryl Sulfonate Amo rphous silica (synthetic) 100.0 C. Compound No. 93 10.0 Sodium lignosulfonate Sodium N-methyl-N-oleyl-taurate Amorphous silica (synthetic) 10.0 Kaolinite clay 100.0 D. Compound No. 96 30.0 Sodium lignosulfonate Scdium dioctyl sulfosuccinate Attapulgit. clay 60.0 Amorphous suilica 100.0 E. Compoud No. 102 75.0 Sodium diociyl sulfosuccinate 1.25 Sodium lignosulfonate Kaolin 10.75 Amorphous silica synthetic 19.9 100.0 F. Compound No. 106 15.0 Sodium lipiosulfonate Sodium N-methyl-N-oleyl-taurate Amorphous silica (synthetic 10.0 Kaolinite clay 7, 100.0 SUBSTIT UTE SHEET WO 92/02509 WO 9202509PCl7/US91/05530 -89- IV, Granules A. Compound No. 36 Dipropylene Glycol Granular attapulgite (24/48 mesh) B. Compound No. 43 Ethylene Glycol (24/48 mesh) Granular Montmorillonite C. compound No. 49 Ethylene glycol Granular Pyrophyllite (24/48 mesh) D. Compound No. 52 Dipropylene Glycol Granular Pyrophyllite (24/48 mesh) E. Compound No. 53 Granular Bentonite (24/48 mesh) F. Compound No. 54 Amorphous silica (synthetic) Granular Montmorillonite (24/48 mesh) G Compound No. 58 Ethylene glycol Granular Montmorillonite (24/48 mesh) H. Compound No. 59 Dipropylene Glycol Granular Bentonite (30/60 mesh) weight Percent 15. 0 80.0 100.*0 S.0 15.0 100.0 94.0 100.0 15. 0 100.0 20.0 80.0Q 100.0 20.0 59.0 10.0 10.0 10.0 10.0 100.0 SUBSTITUTE %SHEET WO 92/02509 PCI'/US9I /05530 We ight Pqeet V. Suspe_9in Concentriates A. Compound No. 66 32.5 Sodium Naphthalene-Formaldehyde Condensate (Morwet D-425) Propylene Glycol 10.*0 Sodium Diisopropyl Naphthalene Sulfonate (Morwet IP) Xanthan Gum (Keizan S) 0.2 Water520 100.0 B. Compound No. 81 37.0 Sodiim Lignin Sulfonate (Polyf on H) EO/PO Block Copolymer (Pluronic P-105) Propylene Glycol 10.0 Xanthan Gum 0.2 Water 4, 100.0 C. Compound No. 83 25.0 Sodium Lignin Sulfonate (Polyf on H) Sodium N-Methyl-N-oleyltaurate (Igepon T-77) Ethylene Glycol 10.0 Xanthan Gum (Rhodopol MD5O) 0.2 Magnesium Aluminum Silicate (Van Gel-B) 0.2 Water 100.0 D. Compound No. 85 30.0 Sodium naphthalene sulfonate formnaldehyde condensate Glycerine Methyl cellulose (Hethocel Al5C) 0.3 M~agnesium Aluminum Silicate (Van Gel B) 0.2 Water 56.5 100.0 SUBSTI ITUTE SHEET WO 92/02509l -91- Wei E. Compound No. 93 Nonyiphenol ethoxylate 9.5 mole EO Sterox NJ sodium lignosulfoflate (Reax 88B) Ethylene Glycol Xanthan Gum Water F. Compound No. 96 Sodium lignin sulfonate (Polyf on F) Ethylene Glycol Xanthan Gum Water G. Compound No. 102 Sodium Naphthalene Sulfonate formaldehyde Condensate Propylene Glycol Snelling Grade Bentonite Antifoam Water V1 Microcapsules (Active ingredient encapsulated within polymeric shell wall) A. Compound No. 69 Polyurea shell wall ReaxQ 88B (dispersant) NaCi (electrolyte) Water PCr/US9I /05530 gh erent 33.0 10.0 0.2 100.0 34.0 10.0 10.0 0.1 100.0 30.0 10.0 100.0 0.4 89.6 100.00 SUBSTITUTE

SHEET

WO 92/02509 -92- B. Compourd No. 81 Polyurea shell wall Reaxe C-21 (dispersant) NaNO 3 (electrolyte)' Aromatic 200 (solvent) Water C. Compound No. 130 Polyurea shell wall Reax* C-21 NaCi Xylene Water D. Compound No. 63 Polyurea shell wall ReaxO 88B NaCi Kerosene E. Compound No. 74 Polyurea shell wall Reax* 88B NaNO 3 Solvent Water PCT/US91 /05530 Weiaht Percent 6.82 45.0 100.00 10.0 40.0 100.0 48.0 4.8 15.0 22-Z 100.0 40.0 10.5 25.0 110 10.0 20.0 54,0 100.0 F. Compound No. 157 Polyurea shell wall ReaxG C-21 NaCi Solvent Water SUBSTITFUTE

SHESET

WO 92/02509 PCF~US91/05530 -93- 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, power dusters, boom and hand sprayers and spray dusters. The compositions can also be applied from airplanes as a dust or a spray because of their effectiveness at low dosages. The exact amount of active ingredient to be employed is dependent upon various factors, including the plant species and stage of development thereof, the type and condition of soil, the amount of rainfall and the specific compounds employed. In selective preemergence, post-emergence and soil applications a dosage of from about 0.0005 kg/ha (0.5 g/ha) to about 11.2 kg/ha is usually employed. A dosage of about 0.001 kg/ha (1.0 g/ha) to about 0.50 kg/ha (500 g/ha) is preferred. Lower or higher rates may be required in some instances. One skilled in the art can readily determine from this specification, including the above examples, the optimum rate to be applied in any particular case.

The term "soil" is employed in its broadest sense to be inclusive of all conventional "soils" as defined in Webster's New International Dictionary, Second Edition, Unabridged (1961). Thus, the term refers to any substance or medium in which vegetation 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 limita- tions.

Various equivalents, changes and modifications may be made without departing from the spirit and scope of this SUBSTITUTE

SHEET

WO 92/02509 -94- WO 920250 PMYUS91/05530 invention, and it is understood that such equivalent embodiments are part of this invention.

SUBSTIT UTE SHEET

Claims

1. Compounds according to Formula II: R7 N (SO)-R, RI wherein R, is hydrogen, C-.5 alkyl optionally substituted with hydrogen or.a R 6 or R7 member; C 3 cycloalkyl optionally substituted with C, alkyl; R 2 is Ci. 5 alkyl optionally substituted with hydrogen or an R, or R7 member; R 3 is hydrogen or halogen; R 5 is halogen and R 6 and R 7 are Ci.g alkyl, haloalkyl, alkylthio, alkoxy- alkyl or polyalkoxyalkyl, C, cycloalkyl, cycloalkenyl, cycloalkyalkyl or cycloalkenylalkyl; C 2 alkenyl or alkynyl; carbamyl, halogen, amino, nitro, cyano, hydroxy, C 4 0 heterocycle containing 1-4 0, S(0)m and/or N hetero atoms, C& 12 aryl, aralkyl or alkaryl, -CXYRg, -CXRI, -CH 2 OCORio, -YRI,, -NRi 2 Ri 3 or any two ccmbinable R6 and members may be 25 combined through a saturated and/or unsaturated carbon, 1 and/or hetero atom linkage to form a heterocyclic ring having up to 9 ring members, which may be substituted with any of said RS-R 7 members or where not self-inclusive said R,-R7 or Rg-RI 3 members substituted with any of said R-C members; provided that when said two canbinable R 6 and R iembers are 96 combined through a -hetero atom linkage, said hetero- cyclic ring has at least six ring members; X is O, S(0)m NR,4 or CR, 5 R, 6 Y is 0 or S(0)mor NR17; are one of said s 5 -R 7 members, and m is 0-2.

2. Compounds according to Claim 1, as defined by formula III: SIII Re O R R 7 N (S02)-R 2 N R, wherein RI and R 2 are C,-5 alkyl; R 3 is hydrogen, bromo, chloro or fluoro; R 5 is halogen; PR is halogen or nitro; R 7 is a member as defined in Claim 1 or R, and R 7 are combined through an -OCH 2 -N- (propynyl)-linkage to form a fused six membered ring.

3. Compounds according to Claim 2 wherein R, and R, are methyl; R 3 is hydrogen, bromo or chloro; S:: R 5 is chloro or fluoro; R, is chloro, fluoro or nitro; 30 R7 is a YR, 1 member as defined in Claim 1 or Ri and R 7 are combined through an -OCH 2 (propynyl)-linkage to give a fused 6 membered ring. 97

4. Compounds according to Claim 1 selected from the group consisting of 4-Chloro-3- (2-f luoro-4-chloro-5- (-2-propynyloxy) phenyl) l-methyl-5- (methylsulfonyl) -1H-pyrazole 4-Broino-3- (2-f luoro-4-chloro-5- (2-propynyloxy) phenyl) (methylsuJlfonyl) -iN-pyrazole 4-Chloro-3- (2-f luoro-4 -chloro-5- (2-methoxyethoxy) phenyl) (methylsulfonyl) -1H-pyrazole 4-Bromo-3- (2-f luoro-4-chloro-5- (2-methoxyethoxy) phenyl) (methylsulfonyl) -1H-pyrazole

6-(4-Chloro--:-methyl-5- (methylsulfonyl) -lH-pyrazol-3-yl) fluoro-4-(2-propynyl)-2H-1,4-benzoxazin-3-(4H)- one (4-Bromo-1-methyl-5- (methylsulfonyl) -lH-pyrazol-3-yl) 2-chloro-4-fluorophenoxy) acetic acid, 1-methyl- ethyl ester (5-(4-Chloro-1-methyl-5-(methylsulfonyl) -lH-pyrazol-3-yl) 2-chloro-4-fluorophenoxy) acetic acid, 1-methyl- ethyl ester 2-(5-(4-Bromo-l-methyl-5-(methylsulfonyl) -1H-pyrazol-3-yl)- 2-chloro-4-fluorophenoxy)propanoic acid, ethyl ester and 2- (4-Chloro-l-methyl-5- (methylsulfonyl) -lli-pyrazol-3- yl) -2-chloro-4-fluorophenoxy)propanoic acid, ethyl ester. 4-Chloro-3- (2-f luoro-4-choro-5-(2-proprnyloey) phenyl) -l-methyl--5-(methylsulfonyl) -lH-pyrazole. 6. 4-Broo-3- (2-f luoro-4-chloro-5-2-propynyloxy)

7. 2- (4-Chloro-l-methyl-5- (methylsulf onyl) -lH- pyrazol-3-yl) -2-chloro-4-fluorophenoxy)propanoic acid, ethyl ester. 98

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

9. Herbicidal composition comprising an adjuvant and a herbicidally effective amount of a compound according to any one of Claims 1-8. Method for combatting undesirable plants in crops which comprises applying to the locus thereof a herbicidally effective amount of a compound according to any one of Claims 1-8, or of a composition according to Claim 9.

11. Process for the preparation of compounds according to Formula II which comprises reacting a compound according to Formula B with an oxidizing agent according to the equation R 5 R R3 R3 O R* 0 R 2 SR 2 oxidation R6. B II R wherein R, is hydrogen, C 1 5 alkyl optionally substituted with an R 7 member; C3 cycloalkyl or cycloalkenyl optionally substituted with CI- alkyl; R 2 is C 1 5 alkyl optionally substituted with an Ry 5 member; R 3 is hydrogen or halogen; R 5 is halogen and R 6 and R7 are independently hydrogen, C 1 -8 alkyl, haloalkyl, alkylthio, alkoxyalkyl or polyalkoxyalkyl, C, cycloalkyl, cyclo- alkenyl, cycloalkyalkyl or cycloalkenylalkyl; C2. alkenyl i /14 99 or alkynyl; carbamyl, halogen, amino, nitro, cyano, hydroxy, C4,, heterocycle containing 1-4 0, S(O)m and/or N hetero atoms, C6i 2 aryl, aralkyl or alkaryl, -CXYR, -CXR), -CH 2 OCORio, -NR, 2 R, or any tic combinable R and PR members may be combined through a saturated and/or unsaturated carbon X 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 7 members or where not self-inclusive said R 7 or R 8 -R, 3 members substituted with any of said R 7 members; provided that when said two caRbinable R 6 and R members are combined through a 0 -hetero atom linkage, said heterocyclic ring has at least six ring members; X is O, S(O)m, NR 14 or CRisR 16 Y is 0 or S(0)mor NR, 7 Ra-R17 are one of said R 7 members; m is 0-2 and n is

12. Process according to Claim 11 wherein in said compounds according to Formula II, l' 2 and R 3 are as defined in Claim 1; R 5 is independently one of said R 3 members and R 6 and R are members as defined in Claim 11 or 4 A 100 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 R. and R 7 members are combined through a 0 11 -hetero atom linkage, said heterocyclic ring has at least six ring members.

13. Process according to Claim 11 wherein said compounds according to Formula II are those as defined for Formula III 1- Q R 3 R, 'N (SO 2 )-R 2 N RI wherein R, and R 2 and are C,. 5 alkyl; R 3 and R 5 are hydrogen, bromo, chloro or fluoro; R is an R 5 member or nitro; R 7 is a member as-defined in Claim 11 or Rs and R, are combined through an -OCHC 2 4 5 linkage to form a fused six-membered ring. i" 14. Process according to Claim 13 wherein R 1 and R 2 and methyl; S R 3 is hydrogen, bromo or chloro; R 5 is chloro or fluoro; PR is chloro, fluoro or nitro and R 7 is a YRn 1 member as defined in Claim 11. e 101 Process according to Claim 11 for the preparation of compounds according to Formula II wherein R 3 is a halogen, which comprises reacting a Formula II compound wherein R 3 is hydrogen with a halogenating agent.

16. Process according to Claim 15 wherein said Formula II compounds prepared by the halogenation process are those as defined for Formula III wherein R 3 is halogen.

17. Process according to Claim 16 wherein R, and R 2 are methyl, R 5 is chloro or fluoro and R. is chloro, fluoro or nitro.

18. Process according to Claim 11 for the preparation of compounds according to FormulaII wherein one of said R7 members is and R 11 is not hydrogen, which comprises reacting the corresponding compound of FormulaII wherein R 1 is hydrogen with an acylating or alkylating agent.

19. Process according to Claim 18 wherein said compound of Formula IIprior to said acylation or alkylation is a compound as defined for Formula III wherein R, is -YH. A compound according to any one of Claims 1 to 8 when prepared by the process of any one of Claims 11 to 19.

21. Herbicidal composition comprising an adjuvant and a herbicidally effective amount of a compound according to Claim .4 I

22. Method for combatting undesirable plants in *crops which comprises applying to the locus thereof a herbicidally effective amount of a compound according to Claim 20, or of a composition according to Claim 21. DATED this 10th day of March 1994 MONSANTO COMPANY, y its Patent Attorneys, E. F. WELNGTON CO., S. Wellington) il. HIELDS SEARCHED Minimum Documentation Searched 7 Classification System Classification Symbols C 07 D Documentation Searched other than Minimum Documentation to the Extent that such Documents are Included in Fields Searched 8 III. DOCUMENTS CONSIDERED TO BE RELEVANT 9 Category* Citation of Document, 11 with indication, where appropriate, of the relevant passages 12 Relevant to Claim No. 1 3 X DE, Al, 2409753 (BASF AG) 11 September 1975, 1,10,19, see the whole document SSpecial categories of cited documents: 10 I' later dopument published after the ipternational filing date A document defining the eneral tate of the art which is not or poriy date and not In conlilct With the appllcalion but Aco ended to be o ra pasrclar the art which is not ied ndertnd the principle or theory underying the considered to be of par icular relevance invention earlier document but published on or after the internationalicular rel e, te filing date document of paricular relevance, the claimed invention cannot be considered novel or cannot be considered to "L document which may throw doubts pn priority claim(s) or involve an inventive step which is cited to establish the publlcation date of anoher aimed i e t citation or other special reason (as specified) document of particular ri evanca, the claimed invention citation or other special reason (as specified) cannot be considered to involve an inventive step when the document referring to an oral disclosure, use, exhibition or document is combined with 9ne or more other such docu- other means ments, such combination being obvious to a person skilled in the art. "P document published prior to the international filing date but document member of the sme patent family later than the priority date claimed document member o the same patent family IV. CERTIFICATION Date of the Actual Completion of the International Search 2nd December 1991 International Searching Authority EUROPEAN PATENT OFFICE Date of Mailing of this International Search Report 1 6 DEC 1991' Form PCTIISA/210 (second sheet) (January 1985) ANNEX TO THE INTERNATIONAL SEARCH REPORT ON INTERNATIONAL PATENT APPLICATION NO.PCT/US 91/05530 SA 50618 This annex lists the patent family members relating to the patent documents cited in the above-mentioed international search report. The members are as contained in the European Patent Office EDP file on 31/10/91 The European Patent office is in no way liable for theseparticulars which are merely given for the purpose of information. Patent document Publication Patent family Publication cited in search report date member(s) date DE-A1- 2409753 11/09/75' AT-B- 340199 25/11/77 BE-A- 826074 27/08/75 CA-A- 1047502 30/01/79 CH-A- 593609 15/12/77 FR-A-B- 2262663 26/09/75 GB-A- 1488285 12/10/77 JP-A- 50117936 16/09/75 NL-A- 7502416 03/09/75 SE-B-C- 413026 31/03/80 SE-A- 7502300 02/09/75 US-A- 4008249 15/02/77 For more details about this annex: see Official Journal of the European patent Office, No. 12182 EPO FORM P0479