WO2000035916A1

WO2000035916A1 - Herbicidal 4-benzoylisoxazoles

Info

Publication number: WO2000035916A1
Application number: PCT/EP1999/010455
Authority: WO
Inventors: Mary Susan Cramp; David William Hawkins; Neil Jonathan Geach; Christopher J. Pearson
Original assignee: Aventis Cropscience S.A.
Priority date: 1998-12-15
Filing date: 1999-12-14
Publication date: 2000-06-22
Also published as: AU2286800A; GB9827617D0

Abstract

The invention relates to compounds of formula (I), wherein R3 represents a 5-membered heteroaromatic ring of formula (II), in which D, E, G and J independently represent CR14¿ or a nitrogen atom, with at least one of D, E, G and J representing CR14, and to their use as herbicides.

Description

HERBICIDAL 4-BENZOYLISOXAZOLES

This invention relates to novel 4-benzoylisoxazole derivatives, compositions containing them, processes for their preparation, intermediates in their preparation and their use as herbicides.

Herbicidal 4-benzoylisoxazoles are described in a number of patent publications for example European Patent Publication Numbers 0418175, 0487357, 0527036, 0527037, 0560482 and 0560483. However none of the above publications disclose or suggest the presence of an aromatic heterocyclic ring linked by a ring nitrogen atom to the benzoyl ring.

The present invention provides 4-benzoylisoxazole derivatives of formula (I):

(I) wherein:

R represents :- lower alkyl, lower haloalkyl; or phenyl substituted or unsubstituted by halogen , lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, nitro, carboxy, lower alkoxycarbonyl or -S(O)pR4;

Ri represents:- lower alkyl or lower haloalkyl; or a cycioalkyl group containing from three to six carbon atoms substituted or unsubstituted by one or more Rl2 groups or one or more halogen atoms;

R2 represents :- halogen; lower alkyl which is substituted by one or more groups -OR⁵; a cycioalkyl group containing from three to six carbon atoms; or a group selected from nitro, cyano, -CO2R⁵, -NR⁵R⁶, -S(O)_pR⁷,

-O(CH2)_mOR5, -COR⁵, -N(R8)SO₂R⁷, -OR⁷, -OH, -OSO₂R⁷,

-(CR9RlO)_tS(O)_qR⁷, -CONR5R6, -N(R8)-C(Z)=Y, -C(R⁹R¹⁰)NR⁸R¹ !, R¹², SF5 and benzyl substituted or unsubstituted by one or more groups Rl-> which may be the same or different; or two groups R², together with adjacent carbon atoms of the phenyl ring form a second phenyl ring or a 5- or 6-membered saturated or unsaturated heterocyclic ring which is fused to the first ring and contains one or two oxygen or sulphur atoms and is unsubstituted or substituted by one or more halogen , lower alkyl, lower haloalkyl or lower alkoxy groups, or one of the ring carbon atoms of the heterocyclic ring forms part of a carbonyl group or an oxime or lower alkoxyimine derivative thereof; (examples of the unsubstituted or substituted fused ring systems when formed include thiochroman, chroman, 2H- thiochromene, 2H-chromene, 4H-thiochromene, 4H-chromene, isothiochroman, isochroman, isothiochromene, isochromene, 1,3- benzodithiole, 1 ,3-benzodioxole, 1,3-benzoxathiole, 1 ,4-benzodithiin, 1 ,4-benzoxathiin, 1,3-benzoxathian, 3,1-benzoxathian and 1 ,3- benzodithian); n represents zero or an integer from one to three; where n is greater than one the groups R² may be the same or different; m represents one, two or three; p, q and r represent zero, one or two; t represents one, two, three or four (preferably one);

R3 represents a 5-membered heteroaromatic ring of formula (II):

— N

(II) in which D, E, G and J independently represent CR*4 or a nitrogen atom, with at least one of D, E, G and J representing CR^4 (when more than one R*4 group is present they may be the same or different);

Rl4 represents a group selected from hydrogen, halogen, R*⁷, nitro, cyano, -CO₂R⁵, -S(O)_pR! ⁶, -OR¹⁶, -NR⁵R⁶ and cyclopropyl; or two adjacent groups CRl4 may form a phenyl or 5- to 7- membered heteroaromatic ring which is fused to the first ring and is unsubstituted or substituted by one or more groups R¹⁵; and when present the 5- to 7- membered heterocyclic ring contains from one to four heteroatoms in the ring which may be the same or different selected from nitrogen, oxygen and sulphur; x represents one or two, when x represents two the R^ groups may be the same or different;

R4 represents lower alkyl or lower haloalkyl;

R⁵ and R" which may be the same or different, each represents hydrogen or R*2;

R⁷ represents :-

R!2; or a cycioalkyl group containing from three to six carbon atoms; or a group -(CH₂)_W- [phenyl unsubstituted or substituted by one or more groups Rl3 which may be the same or different]; w represents zero or one;

R represents:- hydrogen, R⁷, or ORl6;

R9 and R^lO independently represent hydrogen, lower alkyl or lower haloalkyl (preferably containing up to three carbon atoms); R^{1 !} represents -SO₂R⁷ or -C(Z)=Y;

Rl2 represents :- lower alkyl, lower haloalkyl, lower alkenyl, lower haloalkenyl, lower alkynyl or lower haloalkynyl;

Rl3 represents a group selected from halogen, R^⁷, nitro, cyano, -CO₂R⁵, -S(O)_pR¹⁶, -OR¹⁶ and -NR⁵R⁶;

Ri⁵ represents halogen, or R^{l 2};

Rl6 represents lower alkyl or lower haloalkyl;

Ri⁷ represents a straight- or branched- chain alkyl group containing one to three carbon atoms unsubstituted or substituted by one or more halogen atoms;

Y is oxygen or sulphur (preferably Y represents oxygen);

Z represents a group selected from R^₅ -NR1 °R19₃ -SR⁷ and -OR⁷;

Rl8 and R^ independently represent hydrogen or R⁷; and agriculturally acceptable salts thereof, which possess valuable herbicidal properties.

Furthermore in certain cases the substituents R, Ri to R^ and Z may contribute to optical isomerism and/or stereoisomerism. All such forms and isomers thereof, and mixtures thereof are embraced by the present invention.

In the description unless otherwise specified the following terms are generally defined thus:- 'lower alkyl' means a straight- or branched- chain alkyl group having one to six carbon atoms;

'lower haloalkyl' means a straight- or branched- chain alkyl group having one to six carbon atoms, substituted by one or more halogens; 'lower alkoxy' means a straight- or branched- chain alkoxy group having one to six carbon atoms;

'lower haloalkoxy' means a straight- or branched- chain alkoxy group having one to six carbon atoms, substituted by one or more halogens; 'lower alkenyl' means a straight- or branched- chain alkenyl group having two to six carbon atoms;

'lower haloalkenyl' means a straight- or branched- chain alkenyl group having two to six carbon atoms, substituted by one or more halogens; 'lower alkynyl' means a straight- or branched- chain alkynyl group having three to six carbon atoms;

'lower haloalkynyl' means a straight- or branched- chain alkynyl group having three to six carbon atoms, substituted by one or more halogens; 'halogen' means a fluorine, chlorine, bromine or iodine atom.

By the term "agriculturally acceptable salts" is meant salts the cations or anions of which are known and accepted in the art for the formation of salts for agricultural or horticultural use. Preferably the salts are water-soluble. Suitable salts with bases include alkali metal (eg. sodium and potassium), alkaline earth metal (eg. calcium and magnesium), ammonium and amine (eg. diethanolamine, triethanolamine, octylamine, morpholine and dioctylmethylamine) salts. Suitable acid addition salts, formed by compounds of formula (I) containing an amino group, include salts with inorganic acids, for example hydrochlorides, sulphates, phosphates and nitrates and salts with organic acids, for example acetic acid.

The compounds of the invention, in certain aspects of their properties show advantageous properties over known compounds. Compounds in which one R-> group is present are preferred (preferably the R^ group is at the 2- or 4- position on phenyl).

Compounds in which the 2- and 4-positions of phenyl are substituted are also preferred. Preferably R^ is selected from pyrazol-1-yl, imidazol-1-yl, 1,2,4-triazol-l-yl, 1,2,3-triazol-l-yl, l,2,3-triazol-2-yl and 1,2,3,4-tetrazol-l-yl, unsubstituted or substituted by halogen or R ⁷.

In formula (I) above, preferably the 5- and 6- positions of phenyl are unsubstituted.

Preferably R represents lower alkyl or lower haloalkyl.

Preferably Rl represents cyclopropyl or 1 -methylcyclopropyl (cyclopropyl is especially preferred).

Preferably R² represents halogen, a straight- or branched- chain alkyl group containing up to four carbon atoms unsubstituted or substituted by one or more halogen atoms; a group selected from nitro, cyano, -S(O)_pR⁷, -OR⁷ and -CH₂S(O)qR⁷ wherein R⁷ represents lower alkyl or lower haloalkyl; or benzyl unsubstituted or substituted by -S(O)pRl6 wherein R " represents lower alkyl; or two groups R² together with adjacent carbon atoms of the phenyl ring form a second phenyl ring.

Preferably n represents one or two.

N preferred class of compounds of formula (I) above are those wherein: - Ri represents cyclopropyl or 1 -methylcyclopropyl;

R2 represents :- a straight- or branched- chain alkyl group containing up to four carbon atoms unsubstituted or substituted by one or more halogen atoms; or a group selected from halogen, nitro, -S(O)_pR⁷, -OR⁷,

-CH₂S(O)_qR⁷, -CH2ΝR8R¹ * , -N(R⁸)SO₂R⁷ and -N(R⁸)CO₂R⁷; or two groups R2 together with adjacent carbon atoms of the phenyl ring form a second phenyl ring; n represents zero, one or two; x represents one;

R3 represents a 5-membered heteroaromatic ring of formula (II) which is selected from pyrazol-1-yl, imidazol-1-yl, 1 ,2,4-triazol-l-yl, 1,2,3-triazol-l-yl, l,2,3-triazol-2-yl and 1 ,2,3,4-tetrazol-l-yl, , which are substituted by one or two groups R^; R⁷ and R⁸ independently represent lower alkyl or lower haloalkyl;

R¹ 1 represents -SO₂R⁷ or CO₂R⁷; Rl4 represents hydrogen, halogen, a straight- or branched- chain alkyl group containing up to three carbon atoms unsubstituted or substituted by one or more halogen atoms; or -S(O)_pRl ^, NO₂ or

CO R⁵ wherein R⁵ represents lower alkyl; and Ri represents lower alkyl.

A particularly preferred class of compounds of formula (I) above are those wherein:-

R represents lower alkyl or lower haloalkyl; Ri represents cyclopropyl; R2 represents:- halogen; a straight- or branched- chain alkyl group containing up to four carbon atoms unsubstituted or substituted by one or more halogen atoms; or a group selected from -S(O)_pR⁷, -CH₂S(O)qR⁷ and -

OR⁷; or two groups R² together with adjacent carbon atoms of the phenyl ring form a second phenyl ring;

R represents a pyrazol-1-yl, imidazol-1-yl, 1,2,3-triazol-l-yl, l,2,3-triazol-2-yl, 1,2,4-triazol-l-yl or 1,2,3,4-tetrazol-l-yl ring substituted by one or two R*4 groups, wherein R 4 represents hydrogen, optionally halogenated methyl or -S(O)_pRl6; R⁷ and Rl°^" represent methyl or ethyl; and n represents 0, 1 or 2.

A further particularly preferred class of compounds of formula (I) above are those wherein: -

R represents a straight- or branched chain alkyl group containing from one to three carbon atoms;

Ri represents cyclopropyl;

R2 represents :- halogen, methyl, halogenated methyl, -S(O)_pCH3 or OCH3;

R3 represents imidazol-1-yl, 1,2,3-triazol-l-yl, l,2,3-triazol-2-yl or 1,2,4-triazol-l-yl, unsubstituted or substituted on the ring carbon atoms by one or two methyl groups; and n represents one or two.

Particularly important compounds of the invention include: 5 -cyclopropyl-4- [4-( 1 ,2,4-triazol- 1 -yl)-2-trifluoromethylbenzoyl] - 3-(methylthio)isoxazole (Compound 1);

5-cyclopropyl-4-[4-(imidazol-l-yl)-2-trifluoromethylbenzoyl]-3- (methylthio)isoxazole (Compound 2); 5-cyclopropyl-4-[2-methyl-4-(l,2,4-triazol-l-yl)benzoyl]-3- (methylthio)isoxazole (Compound 3);

5-cyclopropyl-4-[2-methyl-4-(imidazol-l-yl)benzoyl]-3- (methylthio)isoxazole (Compound 4); and

5 -cyclopropyl-4- [2-( 1 ,2,4-triazol- 1 -yl)-4-trifluoromethylbenzoyl] - 3-(methylthio)isoxazole (Compound 5).

The following compounds of formula (I) in which Ri represents cyclopropyl and the group (R^)_x is attached either to the 4-position of the phenyl ring (Table 1), or to the 2-position of the phenyl ring (Table

2) form part of the present invention. Note that in the Tables that follow,

Me means methyl, Et means ethyl and Bu means butyl. Where subscripts do not appear in the Table it will be understood that in appropriate cases they are present (e.g. CF3 means CF3 etc.).

TABLE 1

TABLE 2

Compounds of formula (I) may be prepared by the application or adaptation of known methods (i.e. methods heretofore used or described in the literature), for example as hereinafter described.

In the following description where symbols appearing in formulae are not specifically defined, it is to be understood that they are "as hereinbefore defined" in accordance with the first definition of each symbol in the specification.

It is to be understood that in the descriptions of the following processes the sequences may be performed in different orders, and that suitable protecting groups may be required to achieve the compounds sought.

According to a feature of the present invention compounds of formula (I) in which R, R , R2, R3, X and n are as defined above and r represents zero may be prepared by the reaction of a compound of formula (III):

(III) wherein R, R , R2, R3_? X and n are as hereinbefore defined above, with hydroxylamine or a salt of hydroxylamine. Hydroxylamine hydrochloride is generally preferred. The reaction is generally carried out in an organic solvent such as ethanol or acetonitrile or a mixture of a water-miscible organic solvent and water, preferably in a ratio of organic solvent: water of from 1 :99 to 99:1, optionally in the presence of a base or acid acceptor such as triethylamine or sodium acetate at a temperature from room temperature to the boiling point of the solvent. Compounds of formula (III) are novel and as such constitute a further feature of the present invention.

According to a further feature of the present invention compounds of formula (I) wherein R, Rl, R2, R3_; χ₅ n and r are as defined above, may be prepared by the reaction of a compound of formula (IV):

(IV) wherein R, R¹, R R3_{; X? n} and r are as defined above and 7?- represents a leaving group for example halogen (preferably fluoro), with a compound of formula R^-H. The reaction is generally performed in the presence of a base, for example sodium hydride or caesium carbonate, in an inert solvent, for example N,N-dimethylformamide at a temperature from 0°C to 100°C.

Intermediates in the preparation of compounds of formula (I) may be prepared by the application or adaptation of known methods.

Compounds of formula (III) wherein R represents lower alkyl or lower haloalkyl, may be prepared by the reaction of compounds of formula (V):

(V) with carbon disulphide and a compound of formula (VI):

R-L (VI) wherein L is a suitable leaving group generally halogen. The reaction is generally performed in the presence of a base and a solvent such as acetonitrile, N,N-dimethylformamide or dimethylsulphoxide . Suitable bases for the reaction include alkali metal carbonates or hydrides such as potassium carbonate or sodium hydride; or trialkylamines such as triethylamine; or a mixture of potassium fluoride and alumina, according to procedures described by Villemin et. al. in Synthesis 301 (1991); Pak et. al. in Synthesis 793 (1988) and Augustin et. al. in Tetrahedron 32, 3055 (1976).

Compounds of formula (III) wherein R represents optionally substituted phenyl may be prepared by the transketalisation reaction of the corresponding compound of formula (III) wherein R represents lower alkyl or lower haloalkyl using an optionally substituted thiophenol in a solvent such as ethanol, tetrahydrofuran or N,N- dimethylformamide at a temperature of from 20°C to the reflux temperature of the solvent. Compounds of formula (V) may be prepared by the reaction of an acid chloride of formula (VII):

(VII) wherein R2, R3_; X and n are as hereinbefore defined, with a metal salt of a compound of formula (VIII):

(VIII) wherein R is as hereinbefore defined, to give a compound of formula (IX):

O

(IX) wherein Rl, R^, R , X and n are as hereinbefore defined, which is subsequently decarboxylated to give a compound of formula (V). Generally the reaction to produce the compound of formula (IX) is performed in a solvent such as a lower alcohol, preferably methanol, in the presence of a metal, preferably magnesium. The reaction may also be performed using a pre-prepared metal salt of a compound of formula (VIII). The decarboxylation is generally performed by refluxing the compound of formula (IX) in the presence of a catalyst, such as para-toluenesulphonic acid or trifluoroacetic acid, in an inert solvent e.g. toluene or 1,2-dichloroethane.

Compounds of formula (V) may also be prepared by the reaction of a benzoic acid ester of formula (X):

(X) wherein R R3, x and n are as hereinbefore defined and R™ represents a lower alkyl group (preferably methyl), with a compound of formula (XI):

Rl-C(O)-CH₃ (XI) wherein R^ is as hereinbefore defined. The reaction is generally performed in a solvent such as ether, tetrahydrofuran or N,N- dimethylformamide, in the presence of a base, preferably an alkali metal base such as sodium hydride, at a temperature from 0°C to the reflux temperature.

Intermediates of formula (IV) may be prepared by the process described above for the preparation of a compound of formula (I) from the corresponding compound of formula (III).

Acid chlorides of formula (VII) may be prepared by the reaction of a benzoic acid of formula (XII):

(XII) with a chlorinating agent, for example thionyl chloride at the reflux temperature of the mixture. In some cases the benzoyl chlorides may also be prepared by reaction of the benzoic acid with oxalyl chloride in a solvent such as 1 ,2-dichloroethane at from ambient to reflux temperature.

Esters of formula (X) may be prepared from acids of formula (XII) according to known methods.

Benzoic acids of formula (XII) or esters of formula (X) in which R2, R , R20_{5 X} and _{n are as} defined above, may be prepared by the reaction of the corresponding compound of formula (XII) or (X) in which R is replaced by !?^■ (Z^ is as defined above preferably fluorine), with a compound of formula R3-H using the same procedure as described above for the preparation of compounds of formula (I) from compounds of formula (IV).

Intermediates of formula (VI), (VIII), (XI) and (XII), are known or may be prepared by the application or adaptation of known methods. Those skilled in the art will appreciate that some compounds of formula (I) may be prepared by the interconversion of other compounds of formula (I) and such interconversions constitute yet more features of the present invention.

According to a further feature of the present invention compounds in which p, q or r is one or two may be prepared by the oxidation of the sulphur atom of the corresponding compounds in which p, q or r is 0 or

1. The oxidation of the sulphur atom is generally carried out using for example 3-chloroperoxybenzoic acid in an inert solvent such as dichloromethane at a temperature from -40°C to room temperature.

The following non-limiting Examples illustrate the preparation of compounds of formula (I) and the Reference Examples illustrate the preparation of intermediates in their synthesis. NMR Spectra are recorded as d (ppm) in deuterochloroform as solvent (unless otherwise stated) and Mass Spectra refer to Electrospray ES+ where an [M+H] ion is observed. Example 1

Sodium hydride (1.3 equivalents) in dry N,N-dimethylformamide was added to a solution of 1 ,2,4-triazole (125mg) in dry N,N- dimethylformamide and stirred for 0.5 hour. A solution of 5- cyclopropyl-4-(4-fluoro-2-trifluoromethylbenzoyl)-3- (methylthio)isoxazole (500mg) was added and the mixture heated overnight at 50°C. The mixture was added to water, extracted (ethyl acetate) and the organic phase washed with sodium carbonate solution and with water, dried (magnesium sulphate) and evaporated to give 5- cyclopropyl-4-[4-(l,2,4-triazol-l-yl)-2-trifluoromethylbenzoyl]-3- (methylthio)isoxazole (Compound 1 , 510mg), ES+ [M+H] = 395.

By proceeding in a similar manner the following compounds were also prepared:

5-cyclopropyl-4-[4-(imidazol-l-yl)-2-trifluoromethylbenzoyl]-3- (methylthio)isoxazole (Compound 2), ES+ [M+H] = 394; 5-cyclopropyl-4-[2-methyl-4-(l,2,4-triazol-l-yl)benzoyl]-3-

(methylthio)isoxazole (Compound 3), ES+ [M+H] = 341 ; and 5-cyclopropyl-4-[2-methyl-4-(imidazol-l-yl)benzoyl]-3- (methylthio)isoxazole (Compound 4), ES+ [M+H] = 340. Example 2 Hydroxylamine hydrochloride (39 mg) followed by sodium acetate (46 mg) were added to a solution of 3-cyclopropyl-2- [bis(methylthio)methylene]-l-[2-(l,2,4-triazol-l-yl)-4- trifluoromethylphenyl]propan-l ,3-dione (220 mg) in ethanol and stirred overnight. The mixture was evaporated, dissolved in dichloromethane, washed (water), dried (magnesium sulphate) and evaporated. The residue was purified by chromatography on silica gel to give 5-

5 cyclopropyl-4-[2-(l,2,4-triazol-l-yl)-4-trifluoromethylbenzoyl]-3-

(methylthio)isoxazole (Compound 5, 78mg). Reference Example 1

The procedure described in Example 2 was used to prepare the following intermediate compounds: l o 5 -cyclopropyl-4-(4-fluoro-2-trifluoromethylbenzoyl)-3 - methylthio-isoxazole, ES+ [M+H] = 346; and

5-cyclopropyl-4-(4-fluoro-2-methylbenzoyl)-3- (methylthio)isoxazole, ES+ [M+H] = 292. Reference Example 2

15 Triethylamine (15.8ml) then carbon disulphide (3.7ml) were added to a solution of 3-cyclopropyl-l-(4-fluoro-2-methylphenyl)propan-l,3- dione (11.4g) in N,N-dimethylformarnide and stirred for 1.5 hours. A solution of methyl iodide (7.1ml) in N,N-dimethylformamide was added and stirred for 2 days at 20°C. The mixture was added to water,

20 extracted (ethyl acetate) and the extract dried (magnesium sulphate) and evaporated to give 3-cyclopropyl-2-[bis(methylthio)methylene]-l-(4- fluoro-2-methylphenyl)propan-l ,3-dione (1 1.8g).

By proceeding in a similar manner the following compounds were also prepared:

25 3-cyclopropyl-2-[bis(methylthio)methylene]-l-[2-(l,2,4-triazol-l- yl)-4-trifluoromethylphenyl]propan-l,3-dione, ES [M+l] = 428; and

3 -cyclopropyl-2- [bis(methylthio)methy lene] - 1 -(4-fluoro-2- trifluoromethylphenyl)propan- 1 ,3 -dione. Reference Example 3

30 Oxalyl chloride (6.5ml) and a catalytic amount of N,N- dimethylformamide was added to a suspension of 4-fluoro-2- trifluoromethylbenzoic acid (lO.Og) in dry dichloromethane. The mixture was stirred to give a clear solution. Meanwhile a solution of t- butyl 3-cyclopropyl-3-oxopropionate (12.33g) in methanol was added to

35 a stirred mixture of magnesium turnings (1.40g) in methanol. The mixture was heated at 60°C for 0.75 hours, cooled and evaporated. Toluene was added and the mixture was re-evaporated. The residue was redissolved in toluene and the above solution of 4-fluoro-2- trifluoromethylbenzoyl chloride (9.19g) added. The mixture was stirred at 20°C for 24 hours, then hydrochloric acid (2M) added and the stirring continued for a further 1 hour. The organic phase was washed with hydrochloric acid (2 M) and water, dried (magnesium sulphate) and 4- toluenesulphonic acid (0.5g) and toluene were added. The mixture was stirred at reflux for 2 hours, cooled and washed in turn with saturated sodium bicarbonate solution and water, dried (magnesium sulphate) and evaporated to give 3 -cyclopropyl- l-(4-fluoro-2- trifluoromethylphenyl)propan-l,3-dione (11.50g) as a red oil, NMR

1.0(m,2H). 1.2(m,2H), 1.7(m,lH), 5.8(s,lH), 7.2-7.6(m,3H).

By proceeding in a similar manner the following compounds were also prepared:

3 -cyclopropyl- 1 -(4-fluoro-2-methylphenyl)propan- 1 ,3-dione, NMR 0.98(m,2H), 1.20(m,2H), 1.75(m,lH), 2.50(s,3H), 5.90(s,lH),

6.92(m,2H),7.48(m,lH); and

3 -cyclopropyl- 1 - [2-( 1 ,2,4-triazol- 1 -yl)-4- trifluoromethylphenyl]propan-l,3-dione, NMR 0.9(m,2H), l.l(m,.2H), 1.5(m,lH), 3.7(s,lH), 5.5(s,lH), 7.1(d,lH), 7.2(m,lH), 7.7(m,lH), 8.1(s,lH), 8.3(s,lH).

Reference Example 4

A solution of lithium hydroxide monohydrate (94.7g) in water was added to a solution of methyl 2-(l,2,4-triazol-l-yl)-4- trifluoromethylbenzoate (438g) in methanol and stirred at 20°C for 22 hours. The mixture was evaporated, diluted (water), washed (ether) and acidified with hydrochloric acid to give 2-(l,2,4-triazol-l-yl)-4- trifluoromethylbenzoic acid (342g), NMR 7.9-8. l(m,3H), 8.2(s,lH), 9.0(s,lH), 13.6(bs,lH).

Reference Example 5 Potassium carbonate (370g) and 1,2,4-triazole (185g) were added to a mixture of methyl 2-fluoro-4-trifluoromethylbenzoate (496g) in N,N-dimethylformamide. The mixture was stirred at 100°C overnight, evaporated, diluted with water and extracted (dichloromethane). The extract was washed with hydrochloric acid (2M), dried (magnesium sulphate) and evaporated to give methyl 2-(l ,2,4-triazol- 1 -yl)-4- trifluoromethylbenzoate. According to a feature of the present invention, there is provided a method for controlling the growth of weeds (i.e. undesired vegetation) at a locus which comprises applying to the locus a herbicidally effective amount of at least one isoxazole derivative of formula (I) or an agriculturally acceptable salt thereof. For this purpose, the isoxazole derivative is normally used in the form of herbicidal compositions (i.e. in association with compatible diluents or carriers and/or surface active agents suitable for use in herbicidal compositions), for example as hereinafter described. The compounds of formula (I) show herbicidal activity against dicotyledonous (i.e. broad-leafed) and monocotyledonous (i.e. grass) weeds by pre- and/or post-emergence application.

By the term "pre-emergence application" is meant application to the soil in which the weed seeds or seedlings are present before emergence of the weeds above the surface of the soil. By the term "post- emergence application" is meant application to the aerial or exposed portions of the weeds which have emerged above the surface of the soil. For example, the compounds of formula (I) may be used to control the growth of: broad-leafed weeds, for example, Abutilon theophrasti,

Amaranthus retroflexus, Bidens pilosa, Chenopodium album, Galium aparine, Ipomoea spp. e.g. Ipomoea purpurea, Sesbania exaltata, Sinapis arvensis, Solanum nigrum and Xanthium strumarium, and grass weeds, for example Alopecurus myosuroides, Avena fatua, Digitaria sanguinalis, Echinochloa crus-galli. Sorghum bicolor, Eleusine indica and Setaria spp. e.g. Setaria faberii or Setaria viridis. and sedges, for example, Cyperus esculentus. The amounts of compounds of formula (I) applied vary with the nature of the weeds, the compositions used, the time of application, the climatic and edaphic conditions and (when used to control the growth of weeds in crop-growing areas) the nature of the crops. When applied to a crop-growing area, the rate of application should be sufficient to control the growth of weeds without causing substantial permanent damage to the crop. In general, taking these factors into account, application rates from 0.01kg to 2kg of active material per hectare give good results.

However, it is to be understood that higher or lower application rates may be used, depending upon the particular problem of weed control encountered.

The compounds of formula (I) may be used to control selectively the growth of weeds, for example to control the growth of those species hereinbefore mentioned, by pre- or post-emergence application in a directional or non-directional fashion, e.g. by directional or non- directional spraying, to a locus of weed infestation which is an area used, or to be used, for growing crops, for example cereals, e.g. wheat, barley, oats, maize and rice, soya beans, field and dwarf beans, peas, lucerne, cotton, peanuts, flax, onions, carrots, cabbage, oilseed rape, sunflower, sugar beet, and permanent or sown grassland before or after sowing of the crop or before or after emergence of the crop. For the selective control of weeds at a locus of weed infestation which is an area used, or to be used, for growing of crops, e.g. the crops hereinbefore mentioned, application rates from 0.01kg to 1.0kg, and preferably from

0.025kg to 0.25kg, of active material per hectare are particularly suitable.

The compounds of formula (I) may also be used to control the growth of weeds, especially those indicated above, by pre- or post- emergence application in established orchards and other tree-growing areas, for example forests, woods and parks, and plantations, e.g. sugar cane, oil palm and rubber plantations. For this purpose they may be applied in a directional or non- directional fashion (e.g. by directional or non-directional spraying) to the weeds or to the soil in which they are expected to appear, before or after planting of the trees or plantations at application rates from 0.25kg to 2.0kg, and preferably from 0.25kg to 1.0kg of active material per hectare.

The compounds of formula (I) may also be used to control the growth of weeds, especially those indicated above, at loci which are not crop-growing areas but in which the control of weeds is nevertheless desirable.

Examples of such non-crop-growing areas include airfields, industrial sites, railways, roadside verges, the verges of rivers, irrigation and other waterways, scrublands and fallow or uncultivated land, in particular where it is desired to control the growth of weeds in order to reduce fire risks. When used for such purposes in which a total herbicidal effect is frequently desired, the active compounds are normally applied at dosage rates higher than those used in crop-growing areas as hereinbefore described. The precise dosage will depend upon the nature of the vegetation treated and the effect sought.

Pre- or post-emergence application, and preferably pre-emergence application, in a directional or non-directional fashion (e.g. by directional or non-directional spraying) at application rates from 0.5kg to 2.0kg, and preferably from 0.5kg to 1.0kg, of active material per hectare are particularly suitable for this purpose.

When used to control the growth of weeds by pre-emergence application, the compounds of formula (I) may be incorporated into the soil in which the weeds are expected to emerge. It will be appreciated that when the compounds of formula (I) are used to control the growth of weeds by post-emergence application, i.e. by application to the aerial or exposed portions of emerged weeds, the compounds of formula (I) will also normally come into contact with the soil and may also then exercise a pre-emergence control on later-germinating weeds in the soil.

Where especially prolonged weed control is required, the application of the compounds of formula (I) may be repeated if required. According to a further feature of the present invention, there are provided compositions suitable for herbicidal use comprising one or more of the isoxazole derivatives of formula (I) or agriculturally acceptable salts thereof, in association with, and preferably homogeneously dispersed in, one or more compatible agriculturally- acceptable diluents or carriers and/or surface active agents [i.e. diluents or carriers and/or surface active agents of the type generally accepted in the art as being suitable for use in herbicidal compositions and which are compatible with compounds of formula (I)]. The term "homogeneously dispersed" is used to include compositions in which the compounds of formula (I) are dissolved in other components. The term "herbicidal compositions" is used in a broad sense to include not only compositions which are ready for use as herbicides but also concentrates which must be diluted before use. Preferably, the compositions contain from 0.05 to 90% by weight of one or more compounds of formula (I).

The herbicidal compositions may contain both a diluent or carrier and surface-active (e.g. wetting, dispersing, or emulsifying) agent.

Surface-active agents which may be present in herbicidal compositions of the present invention may be of the ionic or non-ionic types, for example sulphoricinoleates, quaternary ammonium derivatives, products based on condensates of ethylene oxide with alkyl and polyaryl phenols, e.g. nonyl- or octyl-phenols, or carboxylic acid esters of anhydrosorbitols which have been rendered soluble by etherification of the free hydroxy groups by condensation with ethylene oxide, alkali and alkaline earth metal salts of sulphuric acid esters and sulphonic acids such as dinonyl- and dioctyl-sodium sulphonosuccinates and alkali and alkaline earth metal salts of high molecular weight sulphonic acid derivatives such as sodium and calcium lignosulphonates and sodium and calcium alkylbenzene sulphonates.

Suitably, the herbicidal compositions according to the present invention may comprise up to 10% by weight, e.g. from 0.05% to 10% by weight, of surface-active agent but, if desired, herbicidal compositions according to the present invention may comprise higher proportions of surface-active agent, for example up to 15% by weight in liquid emulsifiable suspension concentrates and up to 25% by weight in liquid water soluble concentrates.

Examples of suitable solid diluents or carriers are aluminium silicate, talc, calcined magnesia, kieselguhr, tricalcium phosphate, powdered cork, absorbent carbon black and clays such as kaolin and bentonite. The solid compositions (which may take the form of dusts, granules or wettable powders) are preferably prepared by grinding the compounds of formula (I) with solid diluents or by impregnating the solid diluents or carriers with solutions of the compounds of formula (I) in volatile solvents, evaporating the solvents and, if necessary, grinding the products so as to obtain powders. Granular formulations may be prepared by absorbing the compounds of formula (I) (dissolved in suitable solvents, which may, if desired, be volatile) onto the solid diluents or carriers in granular form and, if desired, evaporating the solvents, or by granulating compositions in powder form obtained as described above. Solid herbicidal compositions, particularly wettable powders and granules, may contain wetting or dispersing agents (for example of the types described above), which may also, when solid, serve as diluents or carriers. Liquid compositions according to the invention may take the form of aqueous, organic or aqueous-organic solutions, suspensions and emulsions which may incorporate a surface-active agent. Suitable liquid diluents for incorporation in the liquid compositions include water, glycols, tetrahydrofurfuryl alcohol, acetophenone, cyclohexanone, isophorone, toluene, xylene, mineral, animal and vegetable oils and light aromatic and naphthenic fractions of petroleum (and mixtures of these diluents). Surface-active agents, which may be present in the liquid compositions, may be ionic or non-ionic (for example of the types described above) and may, when liquid, also serve as diluents or carriers.

Powders, dispersible granules and liquid compositions in the form of concentrates may be diluted with water or other suitable diluents, for example mineral or vegetable oils, particularly in the case of liquid concentrates in which the diluent or carrier is an oil, to give compositions ready for use.

Liquid concentrates in which the diluent or carrier is an oil may be used without further dilution using the electrostatic spray technique.

Herbicidal compositions according to the present invention may also contain, if desired, conventional adjuvants such as adhesives, protective colloids, thickeners, penetrating agents, spreading agents, stabilisers, sequestering agents, anti-caking agents, colouring agents and corrosion inhibitors. These adjuvants may also serve as carriers or diluents.

Herbicidal compositions according to the present invention may also comprise the compounds of formula I in association with, and preferably homogeneously dispersed in, one or more other pesticidally active compounds and, if desired, one or more compatible pesticidally acceptable diluents or carriers, surface-active agents and conventional adjuvants as hereinbefore described.

Examples of other pesticidally active compounds which may be included in, or used in conjunction with, the herbicidal compositions of the present invention include herbicides, for example to increase the range of weed species controlled for example alachlor [2-chloro-2,6'- diethyl-N-(methoxy-methyl)-acetanilide], atrazine [2-chloro-4- ethylamino-6-isopropylamino-l ,3,5-triazine], bromoxynil [3,5-dibromo- 4-hydroxybenzonitrile] , chlortoluron [N'-(3 -chloro-4-methylphenyl)- N,N-dimethylurea], cyanazine [2-chloro-4-(l-cyano-l- methylethylamino)-6-ethylamino-l,3,5-triazine], 2,4-D [2,4- dichlorophenoxy-acetic acid], dicamba [3,6-dichloro-2-methoxybenzoic acid], difenzoquat [1,2- dimethyl-3,5-diphenyl-pyrazolium salts], flampropmethyl [methyl N-2-(N- benzoyl-3-chloro-4-fluoroanilino)- propionate], fluometuron [N'-(3-trifluoro- methylphenyl)-N,N- dimethylurea], isoproturon [N'-(4-isopropylphenyl)-N,N-dimethylurea], insecticides, e.g. synthetic pyrethroids, e.g permethrin and cypermethrin, and fungicides, e.g. carbamates, e.g. methyl N-(l-butyl-carbamoyl- benzimidazol-2-yl)carbamate, and triazoles e.g. l-(4-chloro-phenoxy)- 3,3-dimethyl-l-(l,2,4-triazol-l-yl)-butan-2-one.

Pesticidally active compounds and other biologically active materials which may be included in, or used in conjunction with, the herbicidal compositions of the present invention, for example those hereinbefore mentioned, and which are acids, may, if desired, be utilised in the form of conventional derivatives, for example alkali metal and amine salts and esters. The following Examples illustrate herbicidal compositions according to the present invention. The following trade marks appear in the Examples: Synperonic, Solvesso, Arylan, Arkopon, Sopropon, Tixosil, Soprophor, Attagel, Rhodorsil.

Example Cl:

An emulsifϊable concentrate is formed from: Active ingredient (Compound 1) 20% w/v

N-Methylpyrrolidinone (NMP) 25% w/v Calcium dodecylbenzenesulphonate 70%

(CaDDBS) (Arylan CA) 4% w/v

Nonylphenol ethylene oxide propylene oxide condensate (NPEOPO) (Synperonic NPE 1800) 6% w/v Aromatic solvent (Solvesso) to 100 volumes by stirring NMP, active ingredient (Compound 1), CaDDBS,

NPEOPO and Aromatic solvent until a clear solution is formed, and adjusting to volume with Aromatic solvent.

Example C2 A wettable powder is formed from:

Active ingredient (Compound 1) 50% w/w

Sodium dodecylbenzenesulphonate (Arylan SX85) 3% w/w

Sodium methyl oleoyl taurate (Arkopon T) 5% w/w

Sodium polycarboxylate (Sopropon T36) 1% w/w Microfme silicon dioxide (Tixosil 38) 3% w/w

China clay 38% w/w by blending the above ingredients together and grinding the mixture in an air jet mill.

Example C3

A suspension concentrate is formed from:

Active ingredient (Compound 1) 50% w/v

Antifreeze (Propylene glycol) 5% w/v

Ethoxylated tristyrylphenol phosphate

(Soprophor FL) 0.5% w/v

Nonyl phenol 9 mole ethoxylate

(Ethylan BCP) 0.5% w/v

Sodium polycarboxylate (Sopropon T36) 0.2% w/v

Attaclay (Attagel) 1.5% w/v

Antifoam (Rhodorsil AF426R) 0.003% w/v Water to 100 volumes by stirring the above ingredients together and milling in a bead mill.

Example C4

A water dispersible granule is formed from: Active ingredient (Compound 1) 50% w/w

Sodium dodecylbenzenesulphonate

(Arylan SX 85) 3% w/w Sodium methyl oleoyl taurate (Arkopon T) 5% w/w

Sodium polycarboxylate (Sopropon T36) 1% w/w

Binder (Sodium lignosulphonate) 8% w/w

China clay 30% w/w

Microfme silicon dioxide (Tixosil 38) 3% w/w by blending the above ingredients together, grinding the mixture in an air jet mill and granulating by addition of water in a suitable granulation plant (e.g. Fluid bed drier) and drying. Optionally the active ingredient may be ground either on its own or admixed with some or all of the other ingredients. The compounds of the invention have been used in herbicidal applications according to the following procedures.

METHOD OF USE OF HERBICIDAL COMPOUNDS: a) General

Appropriate quantities of the compounds used to treat the plants were dissolved in acetone to give solutions equivalent to application rates of up to lOOOg test compound per hectare (g/ha). These solutions were applied from an automated sprayer delivering the equivalent of 720 litres of spray fluid per hectare.

Two weeks after treatment the plants were assessed for the percentage damage or reduction in growth, compared to untreated control.

TEST METHOD A

Seeds of various broad-leaf and grass weed and crop species were sown, and herbicide dissolved in a mixture of acetone and water was applied at a rate of 250g/ha to the soil surface. The said weeds were Amaranthus retroflexus, Abutilon theophrasti. Ipomoea purpurea. Galium aparine. Setaria viridis. Alopecurus myosuroides, Avena fatua and Echinochloa crus-galli. The crop species used were Soya, Maize, Rice and Wheat.

TEST METHOD B Seeds of the various weed species, as listed in Test Method A, were sown and grown up to a 1-3 leaves stage. A post-emergence application of herbicide dissolved in a mixture of acetone and water was made at a rate of 250g/ha.

Compounds 1-5 of the invention gave at least 80% reduction in growth of one or more weed species in the above Test Methods A or B.

Claims

1. A 4-benzoylisoxazole derivative of formula (I):

(I) wherein:

R represents :- lower alkyl, lower haloalkyl; or phenyl substituted or unsubstituted by halogen , lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, nitro, carboxy, lower alkoxycarbonyl or -S(O)_pR4; i represents :- lower alkyl or lower haloalkyl; or a cycioalkyl group containing from three to six carbon atoms substituted or unsubstituted by one or more R 2 groups or one or more halogen atoms; R2 represents :- halogen; lower alkyl which is substituted by one or more groups -OR⁵; a cycioalkyl group containing from three to six carbon atoms; or a group selected from nitro, cyano, -CO₂R⁵, -NR⁵R6, -S(O)pR⁷, -O(CH₂)_mOR⁵, -COR⁵, -N(R⁸)SO₂R⁷, -OR⁷, -OH, -OSO R⁷,

-(CR⁹R¹⁰)_tS(O)_qR⁷, -CONR5R6, -N(R⁸)-C(Z)=Y, -C(R⁹R¹⁰)NR⁸R¹ !, R¹², SF5 and benzyl substituted or unsubstituted by one or more groups Rl3 which may be the same or different; or two groups R together with adjacent carbon atoms of the phenyl ring form a second phenyl ring or a 5- or 6-membered saturated or unsaturated heterocyclic ring which is fused to the first ring and contains one or two oxygen or sulphur atoms and is unsubstituted or substituted by one or more halogen , lower alkyl, lower haloalkyl or lower alkoxy groups, or one of the ring carbon atoms of the heterocyclic ring forms part of a carbonyl group or an oxime or lower alkoxyimine derivative thereof; (examples of the unsubstituted or substituted fused ring systems when formed include thiochroman, chroman, 2H- thiochromene, 2H-chromene, 4H-thiochromene, 4H-chromene, isothiochroman, isochroman, isothiochromene, isochromene, 1,3- benzodithiole, 1,3-benzodioxole, 1,3-benzoxathiole, 1 ,4-benzodithiin, 1 ,4-benzoxathiin, 1,3-benzoxathian, 3,1-benzoxathian and 1,3- benzodithian); n represents zero or an integer from one to three; where n is greater than one the groups R² may be the same or different; m represents one, two or three; p, q and r represent zero, one or two; t represents one, two, three or four (preferably one); R represents a 5-membered heteroaromatic ring of formula (II):

— N

J^^G

(II) in which D, E, G and J independently represent CRl4 or a nitrogen atom, with at least one of D, E, G and J representing CR^ (when more than one Rl4 group is present they may be the same or different);

Rl4 represents a group selected from hydrogen, halogen, R^⁷, nitro, cyano, -CO₂R⁵, -S(O)_pR¹⁶, -OR¹⁶, -NR⁵R⁶ and cyclopropyl; or two adjacent groups CRl4 may form a phenyl or 5- to 7- membered heteroaromatic ring which is fused to the first ring and is unsubstituted or substituted by one or more groups R^ ⁵; and when present the 5- to 7- membered heterocyclic ring contains from one to four heteroatoms in the ring which may be the same or different selected from nitrogen, oxygen and sulphur; x represents one or two, when x represents two the R^ groups may be the same or different;

R4 represents lower alkyl or lower haloalkyl;

R⁵ and R" which may be the same or different, each represents hydrogen or Rl 2; R⁷ represents :-

Rl2; or a cycioalkyl group containing from three to six carbon atoms; or a group -(CH₂)_W- [phenyl unsubstituted or substituted by one or more groups R*3 which may be the same or different]; w represents zero or one; R⁸ represents : - hydrogen, R⁷, or OR¹⁶; R and RlO independently represent hydrogen, lower alkyl or lower haloalkyl (preferably containing up to three carbon atoms); R¹ ! represents -SO₂R⁷ or -C(Z)=Y;

R!2 represents :- lower alkyl, lower haloalkyl, lower alkenyl, lower haloalkenyl, lower alkynyl or lower haloalkynyl;

Rl represents a group selected from halogen, R¹ , nitro, cyano, -CO R⁵, -S(O)_pR¹⁶, -OR¹⁶ and -NR⁵R6_;

R! 5 represents halogen, or Rl2; R¹" represents lower alkyl or lower haloalkyl;

R¹⁷ represents a straight- or branched- chain alkyl group containing one to three carbon atoms unsubstituted or substituted by one or more halogen atoms;

Y is oxygen or sulphur (preferably Y represents oxygen); Z represents a group selected from R12, -NR¹⁸R¹⁹ ₅ -SR? and

-OR⁷;

R¹⁸ and R¹⁹ independently represent hydrogen or R⁷; and agriculturally acceptable salts thereof.

2. A compound according to claim 1 in which R3 is selected from pyrazol-1-yl, imidazol-1-yl, 1,2,4-triazol-l-yl, 1,2,3-triazol-l-yl, l,2,3-triazol-2-yl and 1,2,3,4-tetrazol-l-yl, unsubstituted or substituted by halogen or R¹⁷.

3. A compound according to claim 1 or 2 in which R¹ represents cyclopropyl or 1 -methylcyclopropyl 4. A compound according to claim 1, 2 or 3 in which R² represents halogen, a straight- or branched- chain alkyl group containing up to four carbon atoms unsubstituted or substituted by one or more halogen atoms; a group selected from nitro, cyano, -S(O)_pR⁷, -OR⁷ and

-CH S(O)qR⁷ wherein R⁷ represents lower alkyl or lower haloalkyl; or benzyl unsubstituted or substituted by -S(O)_pR¹⁶ wherein R¹⁶ represents lower alkyl; or two groups R² together with adjacent carbon atoms of the phenyl ring form a second phenyl ring.

5. A compound according to any one of the preceding claims in which R¹ represents cyclopropyl or 1 -methylcyclopropyl; R2 represents:- a straight- or branched- chain alkyl group containing up to four carbon atoms unsubstituted or substituted by one or more halogen atoms; or a group selected from halogen, nitro, -S(O)_pR⁷, -OR⁷, -CH₂S(O)_qR⁷, -CH₂NR⁸R! 1 , -N(R⁸)SO₂R⁷ and -N(R )CO₂R⁷; or two groups R2 together with adjacent carbon atoms of the phenyl ring form a second phenyl ring; n represents zero, one or two; x represents one; R^ represents a 5-membered heteroaromatic ring of formula (II) which is selected from pyrazol-1-yl, imidazol-1-yl, 1 ,2,4-triazol-l-yl, 1,2,3-triazol-l-yl, l,2,3-triazol-2-yl and 1,2,3,4-tetrazol-l-yl, which are substituted by one or two groups R¹^;

R⁷ and R⁸ independently represent lower alkyl or lower haloalkyl; R¹ ! represents -SO₂R⁷ or CO R⁷;

Rl4 represents hydrogen, halogen, a straight- or branched- chain alkyl group containing up to three carbon atoms unsubstituted or substituted by one or more halogen atoms; or -S(O)pR^{1 (}\ NO or

CO₂R⁵ wherein R⁵ represents lower alkyl; and R¹⁶ represents lower alkyl.

6. A compound according to any one of the preceding claims in which R represents a straight- or branched chain alkyl group containing from one to three carbon atoms;

Ri represents cyclopropyl; R2 represents :- halogen, methyl, halogenated methyl, -S(O)pCH3 or OCH3;

7. A herbicidal composition comprising an effective amount of a 4-benzoylisoxazole derivative according to any one of claims 1 to 6 or an agriculturally acceptable salt thereof, in association with an agriculturally acceptable diluent or carrier and/or surface active agent.

8. A method for the control of weeds at a locus which comprises applying to said locus an effective amount of 4- benzoylisoxazole derivative according to any one of claims 1 to 6 or an agriculturally acceptable salt thereof or a herbicidal composition according to claim 7.

9. A method according to claim 8 wherein the locus is an area used, or to be used, for the growing of crops and the 4-benzoylisoxazole derivative or salt thereof is applied at an application rate of from 1 g to 1000 g/ha.

10. A process for the preparation of a 4-benzoylisoxazole derivative of formula (I) as defined in claim 1 which comprises:

(a) where r represents zero the reaction of a compound of formula (III):

(III)

wherein R, R¹, R², R3, X and n are as defined in claim 1, with hydroxylamine or a salt of hydroxylamine;

(b) the reaction of a compound of formula (IV):

wherein R, R¹, R R , x, n and r are as defined above and 2?- represents a leaving group, with a compound of formula R3-H; and

(c) where p, q or r is one or two, the oxidation of the sulphur atom of the corresponding compounds in which p, q or r is 0 or 1 ; optionally followed by the conversion of the compound of formula (I) thus obtained into an agriculturally acceptable salt thereof.

11. A compound of formula (III):

(III)

wherein R, R¹ , R², R , x and n are as defined in claim 1.