WO1995025105A1 - Isoxazole derivatives and their use as herbicides - Google Patents

Abstract

The invention relates to isoxazoles of formula (I) wherein: Ar represents a monocyclic or fused bicyclic heterocyclic system Het having a non-pyridyl heterocyclic first ring and an optional second heterocyclic or carbocyclic ring, the second ring when present being fused to the first ring, the first ring having from 1 to 4 hetero ring atoms and from 4 to 7 total ring atoms, the first ring being aromatic or non-aromatic and being optionally substituted by from 1 to 4R2 groups which may be the same or different, the second ring being optionally substituted by from 1 to 4 R2 groups which may be the same or different; R represents the hydrogen atom or a group -CO¿2R?3; R1 represents: a straight- or branched- chain alkyl group containing from one to six carbon atoms which is optionally substituted by one or more halogen atoms; or a cycloalkyl group containing from three to six carbon atoms optionally substituted by one or more groups selected from R4, -CO2R4, -SR4, halogen and -OR4; R2 represents: a halogen atom; a straight- or branched-chain alkyl group containing from one to six carbon atoms which is substituted by a group -OR4; or a group selected from -OH, R?4, -SR5, -SOR5, -SO¿2R5, -O-SO¿2?R?5, -CO¿2R?4, -COR4, -OR5, -NR6R7, -N(R8)SO¿2R5, nitro, cyano, -O(CH¿2?)m-OR?4, -(-CR9R10-)¿t-S(O)pR5 and -NR11R12; and to their use as herbicides.

Description

IS0XAZ0LE DERIVATIVES AND THEIR USE AS HERBICIDES

TECHNICAL FIELD

This invention relates to novel isoxazole derivatives, compositions containing them, processes for their preparation and their use as herbicides. BACKGROUND ART

Herbicidal 4-benzoylisoxazoles are known in the literature, for example see European Patent Publication Nos. 0418175 and 0487357. Herbicidal 4-Alkylcarbonyl or 4-cycloalkylcarbonyl isoxazoles substituted in the 5-position by optionally substituted phenyl or pyridyl are known from European Patent Publication No.

0524018.

DESCRIPTION OF THE INVENTION The present invention provides isoxazoles of formula I:

(I) wherein:

AT represents a monocyclic or fused bicyclic heterocyclic system Het having a non-pyridyl heterocyclic first ring and an optional second heterocyclic or carbocyclic ring, the second ring when present being fused to the first ring, the first ring having from 1 to 4 hetero ring atoms and from 4 to 7 total ring atoms, the hetero ring atoms preferably being selected from oxygen, nitrogen and sulphur, the first ring being aromatic or non-aromatic and being optionally substituted by from 1 to 4 R2 groups which may be the same or different, the second ring being optionally substituted by from 1 to 4 R2 groups which may be the same or different;

R represents the hydrogen atom or a group -CC^R- ; Rl represents:- a straight- or branched- chain alkyl group containing from one to six carbon atoms which is optionally substituted by one or more halogen atoms; or a cycloalkyl group containing from three to six carbon atoms optionally substituted by one or more groups selected from R⁴, -C0₂R⁴, -SR⁴, halogen and -OR⁴;

R2 represents:- a halogen atom, a straight- or branched- chain alkyl group containing from one to six carbon atoms which is substituted by a group -OR⁴; or a group selected from -OH, R⁴, -SR⁵, -SOR⁵, -SO2R⁵, -0-S0₂R⁵, -C0₂R⁴, -COR⁴, -OR⁵, -NR6R -N(R8)S0₂R⁵, nitro, cyano, -0(CH₂)_m-OR⁴, -(-CR⁹R¹⁰-)_t-S(O)_pR⁵ and -NR R¹²; when the first and/or second ring of Het is non-aromatic, then

R2 may also represent =0, =S, cyclic ketal or cyclic thioketal;

R3 and R⁴, which may be the same or different, each represent a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to six carbon atoms which is optionally substituted by one or more halogen atoms;

R⁵ represents a group R⁴, or phenyl optionally substituted by from one to five groups which may be the same or different selected from halogen, R⁴, -C0₂R⁴, -COR⁴, -OR⁴, nitro, cyano and -0(CH₂)_m-OR⁴; R6 and B7, which may be the same or different, each represent the hydrogen atom or a straight- or branched- chain alkyl group containing from one to six carbon atoms which is optionally substituted by one or more halogen atoms; m represents an integer from one to three; R8 represents the hydrogen atom; a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to six carbon atoms optionally substituted by one or more halogen atoms; a cycloalkyl group containing from three to six carbon atoms; or phenyl optionally substituted by from one to five groups R² which may be the same or different;

R9 and R*0, which may be the same or different, each represents: the hydrogen atom; a straight- or branched-chain alkyl group containing up to 6 carbon atoms which is optionally substituted by one or more halogen atoms; or phenyl optionally substituted by from one to five groups which may be the same or different selected from halogen, R⁴, -CO2R⁴, -COR⁴, -OR⁴, nitro, cyano and -0(CH₂)_m-OR⁴; p is zero, 1 or 2; t represents an integer from one to three;

R¹¹ represents -COR⁴ or -C0₂R⁴;

Rl2 represents:- the hydrogen atom; a straight- or branched- chain alkyl group containing up to six carbon atoms optionally substituted by one or more halogen atoms; or a cycloalkyl group containing from three to six carbon atoms; and agriculturally acceptable salts thereof, which possess valuable herbicidal properties.

In certain cases the substituents R, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹ and R¹² contribute to optical isomerism and/or stereo isomerism. All such forms are embraced by the present invention.

By the term "agriculturally acceptable salts" is meant salts the cations 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 acid addition salts formed by compounds of formula I include salts with inorganic acids, for example hydrochlorides, sulphates, phosphates and nitrates and salts with organic acids, for example acetic acid.

It will be understood in the definition of Het, where the first heterocyclic and/or the second ring contains a sulphur atom in the ring, the sulphur atom may be in the form of a group -SO- or -S0₂-.

Where Het is a fused bicyclic heterocyclic system either the heterocyclic first ring or the second ring may be attached to the 5-position of the isoxazole ring. Where R² represents cyclic ketal or cyclic thioketal preferably the ketal or thioketal ring contains 5 or 6 ring members.

Examples of the group Het because of their herbicidal properties include the following: thienyl, furyl, pyrrolyl and their benzo-fused analogues; oxazinyl, thiazinyl, pyrazinyl, pyrimidinyl, pyridazinyl and their benzo-fused analogues; thiazolyl, oxazolyl, imidazolyl and their benzo-fused analogues; pyrazolyl, isoxazolyl, isothiazolyl and their benzo-fused analogues; oxadiazolyl, thiadiazolyl, triazolyl and, where appropriate, their benzo-fused analogues; pyranyl, thiinyl and their benzo-fused analogues; oxadiazinyl, thiadiazinyl, triazinyl and, where appropriate, their benzo-fused analogues; tetrazolyl, piperidinyl, mo holinyl and piperazinyl.

Due to their herbicidal properties, compounds of formula I in which Ar represents optionally substituted 1,3-benzodioxole, benzo[b]thiophene, 1,3-benzoxathiole, 3,3-dioxo-l,3-benzoxathiole, or benzoxazole are preferred (especially optionally substituted 1,3-benzodioxole, benzo[b]thiophene or benzoxazole).

Compounds of formula I in which Ar represents optionally substituted pyrazolyl or thienyl are also preferred in view of their herbicidal properties.

Compounds of formula I in which R represents hydrogen are also preferred.

Preferably R* represents a straight- or branched- chain alkyl group containing up to four carbon atoms; or a cyclopropyl group optionally substituted by a group R⁴ (especially where R⁴ is alkyl). More preferably R¹ represents 1-methylcyclopropyl or, most preferably, cyclopropyl.

Preferably R² represents a halogen atom or a group selected from -SR⁵, -SOR⁵, -S0₂R⁵, -CH₂S(0)_pR⁵, -CC^R⁴ and -OR⁵.

Compounds of formula I are also preferred in which R² represents a halogen atom or a group selected from -SR⁵, -SOR⁵, -S0₂R⁵, -CH₂S(0)_pR⁵, -C0₂R⁴, R⁵ and -OR⁵ are also preferred.

Compounds of formula I in which R² represents: a halogen atom (e.g. fluorine, chlorine or bromine); alkyl containing up to four carbon atoms optionally substituted by one or more fluorine atoms (e.g. methyl, t-butyl or -CF3); or a group selected from -SMe, -SOMe, -S0₂Me, -C0₂Me and -OMe. Compounds of formula I in which R⁵ represents a straight- or branched- chain alkyl group containing from one to six carbon atoms are also preferred, most preferably methyl.

Preferably Ar represents a group Het which is optionally substituted by from one to three groups R². Particularly important compounds of formula (I) because of their herbicidal properties include the following:

1. 4-cyclopropylcarbonyl-5-(2,2-difluoro-l,3-benzodioxol- 4-yl)isoxazole;

2. 5-(2-t-butyl-4-chlorobenzoxazol-7-yl)-4-cyclopropyl- carbonylisoxazole;

3. 4-cyclopropylcarbonyl-5-(7-methylsulphenyl- 1,3- benzodioxol-4-yl)isoxazole;

4. 4-cyclopropylcarbonyl-5-(7-methylsulphinyl- 1,3- benzodioxol-4-yl)isoxazole ; 5. 4-cyclopropylcarbonyl-5-(7-methylsulphonyl-l,3- benzodioxol-4-yl)isoxazole;

6. 4-cyclopropylcarbonyl-5-( l-ethyl-3-trifluoromethyl- pyrazol-4-yl)isoxazole;

7. 4-cyclopropylcarbonyl-5-(4,5-dibromo-3- methylsulphenylthien-2-yl)isoxazole;

8. 4-cyclopropylcarbonyl-5-(3,4-dimethoxy-5- methoxycarbonylbenzo[b]thien-2-yl)isoxazole;

9. 4-cyclopropylcarbonyl-5-(3,4-dimethoxy- 1, l-dioxo-5- methoxycarbonylbenzo[b]thien-2-yl)isoxazole; 10. 5-(4-chloro-3-methoxy-2-methylbenzo[b]thien-7-yl)-4- cyclopropylcarbonylisoxazole;

11. 5-(4-chloro-l,l-dioxo-3-methoxybenzo[b]tbien-7-yl)-4- cyclopropylcarbonylisoxazole;

12. 5-(7-bromo- l,3-benzoxathiol-4-yl)-4- cyclopropylcarbonylisoxazole;

13. 5-(7-bromo-3,3-dioxo- l,3-benzoxathiol-4-yl)-4- cyclopropylcarbonylisoxazole.

The numbers 1 to 13 are assigned to these compounds for reference and identification hereinafter. 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.

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) may be prepared by the metallation of a compound of formula (II):

(H) wherein Ar and R are as hereinbefore defined and X is a halogen atom, followed by reaction of the compound thus obtained with an acid chloride of general formula RlCOCl, wherein R¹ is as hereinbefore defined. Generally X is bromine or iodine and the reaction performed with for example n-butyl lithium in an inert solvent such as ether or tetrahydrofuran at a temperature from -78⁰C to (PC.

According to a further feature of the present invention compounds of formula I in which R represents hydrogen may be prepared by the reaction of a compound of formula (III):

(HI) wherein Ar and Rl are as hereinbefore defined and L is a leaving group, with a salt of hydroxylamine. Hydroxylamine hydrochloride is generally preferred. Generally L is alkoxy, for example ethoxy, or N,N-dialkylamino, for example N,N-dimethylamino. The reaction is generally carried out in a solvent such as ethanol or acetonitrile, optionally in the presence of a base or acid acceptor such as triethylamine or sodium acetate.

According to a further feature of the present invention compounds of formula I in which R represents hydrogen may be prepared by the reaction of a compound of formula (IV):

(IV) wherein Ar is as hereinbefore described and Y represents a carboxy group or a reactive derivative thereof (such as a carboxylic acid chloride or carboxylic ester), or a cyano group, with an organometallic reagent of formula Rl-M wherein R is as hereinbefore defined and M represents an alkali metal, a metal bonded to one or more ligands, or a Grignard group. Preferably M represents lithium, or a magnesium-containing Grignard group. The reaction is generally carried out in an inert solvent such as diethyl ether or tetrahydrofuran at a temperature from -78°C to the reflux temperature of the mixture. According to a further feature of the present invention compounds of formula I wherein R represents a group -C0 R³ may be prepared by the reaction of a compound of formula (V):

(V) wherein Ar and Rl are as hereinbefore defined and P is a leaving group, with a compound of formula R³0₂CC(X) =NOH wherein R^ is as hereinbefore defined and X is a halogen atom. Generally X is chlorine or bromine and P represents N,N-dialkylamino. The reaction is generally performed in an inert solvent such as toluene or dichloromethane either in the presence of a base such as triethylamine or a catalyst such as a 4 Angstrom molecular sieve or fluoride ion.

According to a further feature of the present invention compounds of formula I in which R represents a group -CC^R³ may be prepared by the reaction of a compound of formula (VI):

wherein Ar and Rl are as hereinbefore defined, with a compound of formula R3O₂CC(X) =NOH wherein R³ and X are as hereinbefore defined. The reaction is generally performed in an inert solvent such as toluene or dichloromethane optionally in the presence of a base such as triethylamine or a catalyst such as a 4 Angstrom molecular sieve or fluoride ion. The reaction can be carried out at a temperature between room temperature and the reflux temperature of the mixture.

According to a further feature of the present invention compounds of formula I wherein R represents -C0₂R³ may be prepared by the reaction of the salt of a compound of formula (VII):

O O

Ar^ ^Rl <™ wherein Ar and R are as hereinbefore defined, with a compound of formula R³0₂CC(X) =NOH wherein R³ and X are as hereinbefore defined. Preferred salts include sodium or magnesium salts. The reaction may be performed in an inert solvent such as dichloromethane or acetonitrile at a temperature between room temperature and the reflux temperature of the mixture.

Intermediates in the preparation of compounds of formula I may be prepared by the application or adaptation of known methods, for example as described hereinafter.

Compounds of formula (III) in which L represents O-alkyl or N,N-dial_kylamino may be prepared by the reaction of the corresponding compound of formula (VII) with either a trialkyl orthoformate such as triethyl orthofoπnate or a dimethylformamide dialkylacetal such as N,N-dimethylfoπnamide dimethyl acetal. The reaction with triethyl orthoformate is generally carried out in the presence of acetic anhydride at the reflux temperature of the mixture and the reaction with N,N-dimethyl formamide dialkyl acetal is carried out optionally in the presence of an inert solvent at a temperature from room temperature to the reflux temperature of the mixture.

Compounds of formula (V) may be prepared by reacting a compound of formula (VIE) with an acid chloride of formula (IX):

(VIII) (IX) wherein Ar, Rl and P are as hereinbefore defined. The reaction is generally carried out in the presence of an organic base such as triethylamine in an inert solvent such as toluene or CH₂C1₂ at a temperature between -20°C and room temperature.

Compounds of formula (VI) may be prepared by the metallation of the appropriate acetylene of formula (X):

Ar-OCH (X) wherein R is as hereinbefore defined, followed by reaction of the metal salt thus obtained with an acid chloride of formula (IX). The metallation is generally performed using n-butyl lithium in an inert solvent such as ether or tetrahydrofuran at a temperature from -78°C to 0°C The subsequent reaction with the acid chloride is carried out in the same solvent at a temperature between -78°C and room temperature.

Compounds of formula (VII) may be prepared by the reaction of an ester of formula (XI):

R!-C0₂Z (XI) wherein Rl is as hereinbefore defined and Z is an alkyl group, with a ketone of formula ArC(0)CH3, wherein Ar is as hereinbefore defined in the presence of a base. Generally the base used is sodium hydride and the reaction is performed in an inert solvent at a temperature from 0°C to reflux. Compounds of formula (VII) may also be prepared by the reaction of a compound of formula (XII):

Rl-COCH₃ (Xπ) wherein R is as hereinbefore defined, with an ester of formula ArC0 Z , wherein Ar and Z are as hereinbefore defined, in the presence of a base. Preferably Z represents a methyl, ethyl or t-butyl group. Generally the base used is sodium hydride and the reaction is performed in an inert solvent at a temperature from 0°C to reflux.

Compounds of formula (VII) may also be prepared by the reaction of an acid chloride of formula (IX) with the metal salt of a compound of formula (XIII):

ArC(0)CH₂C0₂tBu (XIII) wherein Ar is as hereinbefore defined, to give a compound of formula (XIV):

wherein R is as hereinbefore defined, which is decarboxylated to give a compound of formula (VII). Generally the reaction to produce the compound of formula (XTV) is performed in a solvent such as a lower alcohol, preferably methanol, in the presence of a metal, preferably magnesium. The decarboxylation is generally performed by refluxing the compound of formula (XIV) in the presence of a catalyst, such as para-toluenesulphonic acid, in an inert solvent e.g. toluene.

Intermediates of formula (II), (IV), (VJΗ), (IX), (X), (XI), (XII), and (XIII) 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 inter conversion of other compounds of formula I and such inter conversions constitute yet more features of the present invention. Examples of such interconversions are hereafter described.

According to a further feature of the present invention compounds in which R² represents -SOR⁵ or -SO2R⁵ may be prepared by the oxidation of the sulphur atom of the corresponding compound in which R² represents -SR⁵ or -SOR⁵. According to a further feature of the invention compounds of formula (I) in which a ring member of the group Het is -SO- or -S0₂- may be prepared by the oxidation of the ring sulphur atom of the corresponding compound of formula (I). The oxidation of the sulphur atom is generally carried out using for example 3-chloroperoxy-benzoic acid in an inert solvent such as dichloromethane at a temperature from -40°C to room temperature.

The following Examples illustrate the preparation of compounds of formula I and the following Reference Examples illustrate the preparation of intermediates of the invention. In the present specification b.p. means boiling point; m.p. means melting point. Where the letters NMR appear, there follow the characteristics of a proton nuclear magnetic spectrum.

Example 1

A solution of 3-cyclopropyl-2-dimethylaminomethylene-l-(2,2- difluoro-l,3-benzodioxol-4-yl)propan-l,2-dione (lO.Og) in ethanol (50ml) was stirred overnight with hydroxylamine hydrochloride

(2.37g). Water was added and the mixture extracted with ethyl acetate, washed (brine), dried (sodium sulphate) and evaporated. Purification by chromatography on silica gel eluting with ethyl acetate/cyclohexane gave 4-cyclopropylcarbonyl-5-(2,2-difluoro-l,3- benzodioxol-4-yl)isoxazole (compound 1, 2.48g) as a white solid, m.p. 92-95°C

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

4-cyclopropylcarbonyl-5-(7-methylsulphenyl-l,3-benzodioxol-4- yl)isoxazole (compound 3), m.p. 139-140°C;

5-(7-bromo-l,3-benzoxathiol-4-yl)-4- cyclopropylcarbonylisoxazole (compound 12), m.p. 138-139°C.

Example 2 Hydroxylamine hydrochloride (0.25g) and sodium acetate

(anhydrous, 0.3g) were added to a solution of 3-cyclopropyl-l-(4,5- dibromo-3-methylsulphenylthien-2-yl)-2-ethoxymethylenepropan- 1,3-dione (1.46g) in ethanol (4ml). After stirring for 1 hour at room temperature, water was added, and the mixture extracted (dichloromethane). The extract was washed (water), dried

(magnesium sulphate) and evaporated. Purification by chromatography on silica gel eluting with hexane/ethyl acetate (6:1) gave 4-cyclopropylcarbonyl-5-(4,5-dibromo-3-methylsulphenylthien- 2-yl)isoxazole (compound 7), m.p. 105-107°C By proceeding in a similar manner the following compounds were prepared:

5-(2-t-butyl-4-chlorobenzoxazol-7-yl)-4- cyclopropylcarbonylisoxazole (compound 2), NMR (CDCI3) δ 0.96(2H,m), 1.25(2H,m), 1.50(9H,s), 2.15(lH,m), 7.46(lH,d), 7.79(lH,d), 8.78(lH,s);

4-cyclopropylcarbonyl-5-(3,4-dimethoxy-5- methoxycarbonylbenzo[b]thien-2-yl)isoxazole (compound 8), NMR

(CDCI3) δ 0.93(2H,m), 1.19(2H,m), 2.09(lH,m), 3.86(3H,s), 3.87(3H,s), 3.95(3H,s), 7.50(lH,d), 7.83(lH,d), 8.65(lH,s).

4-cyclopropylcarbonyl-5-(l-ethyl-3-trifluoromethylpyrazol-4- yl)isoxazole (compound 6), m.p. 79-81°C;

Example 3 m-Chloroperbenzoic acid (55%, 0.88g) was added to a stirred solution of 4-cyclopropylcarbonyl-5-(7-methylsulphenyl-l,3- benzodioxol-4-yl)isoxazole (0.9g) in dichloromethane (20ml) at -15°C. After 2 hours at 0°C, the mixture was filtered and the filtrate treated with sodium metabisulphite solution and re-filtered. The filtrate was washed with sodium acetate solution, then with brine, dried (sodium sulphate) and evaporated. The residue was triturated with cyclohexane to give 4-cyclopropylcarbonyl-5-(7- methylsulphinyl-l,3-benzodioxol-4-yl)isoxazole (compound 4), m.p.

130-133°C.

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

4-cyclopropylcarbonyl-5-(7-methylsulphonyl-l,3-benzodioxol- 4-yl)isoxazole (compound 5), m.p. 188-189°C, from 4- cyclopropylcarbonyl-5-(7-methylsulphinyl-l,3-benzodioxol-4- yl)isoxazole;

4-cyclopropylcarbonyl-5-(3,4-dimethoxy-l,l-dioxo-5- methoxycarbonylbenzo[b]thien-2-yl)isoxazole (compound 9), NMR(CDCl3) δ 0.96(2H,m), 1.18(2H,m), 2.38(lH,m), 3.78(3H,s),

3.88(6H,2s), 7.53(lH,d), 7.96(lH,d), 8.72(lH,s) from 4- cyclopropylcarbonyl-5-(3,4-dimethoxy-5- methoxycarbonylbenzo[b]thien-2-yl)isoxazole.

5-(4-chloro-l,l-dioxo-3-methoxybenzo[b]thien-7-yl)-4- cyclopropylcarbonylisoxazole (compound 11), m.p. 186.5- 189.5°C;

5-(7-bromo-3,3-dioxo-l,3-benzoxathiol-4-yl)-4- cyclopropylcarbonylisoxazole (compound 13), m.p. 214-215°C Reference Example 1

A solution of 4-(3-cyclopropyl-l,3-dioxoprop-l-yl)-2,2-difluoro- 1,3-benzodioxole (12.0g) in dry toluene was treated with N,N- dimethylformamide dimethyl acetal and the mixture stirred overnight. After evaporation in vacuo and re-evaporation after addition of toluene, the residue was recrystallised from cyclohexane- ethanol to give 4-(3-cyclopropyl-2-dimethylaminomethylene-l,3- dioxoprop-l-yl)-2,2-difluoro-l,3-benzodioxole (6.5g) as a pale yellow solid, m.p. 118-119°C

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

4-(3-cyclopropyl-2-dimethylaminomethylene-l,3-dioxoprop-l- yl)-l-ethyl-3-trifluoromethylpyrazole. 4-(3-cyclopropyl-2-dimethylaminomethylene-l,3-dioxoprop-l- yl)-2,2-difluoro-7-methylsulphenyl-l,3-benzodioxole.

7-bromo-4-(3-cyclopropyl-2-dimethylaminomethylene-l,3- dioxoprop- 1-yl)- 1,3-benzoxathiol.

Reference Example 2

A mixture of 2,3-dibromo-5-(3-cyclopropyl-l,3-dioxoprop-l- yl)-4-methylsulphenylthiophene (1.22g), triethyl orthoformate (0.9 lg) and acetic anhydride (0.93g) was heated at reflux for 2 hours. The mixture was evaporated in vacuo to give 2,3-dibromo-5- (3-cyclopropyl-2-ethoxymethylene-l,3-dioxoprop-l-yl)-4- methylsulphenylthiophene (1.46g) as a brown oil, used in the next stage without purification.

By proceeding in a similar manner the following compounds were prepared: 2-t-butyl-4-chloro-7-(3-cyclopropyl-2-ethoxymethylene- 1,3- dioxoprop- l-yl)benzoxazole. methyl 2-(3-cyclopropyl-2-ethoxymethylene-l,3-dioxoprop-l- yl)-3,4-dimethoxybenzo[b]thiophene-5-carboxylate. 4-chloro-3-methoxy-2-methyl-7-(3-cyclopropyl-2- ethoxymethylene-l,3-dioxoprop-l-yl)benzo[b]tbiophene.

4-chloro-3-methoxy-7-(3-cyclopropyl-2-ethoxymethylene-l,3- dioxoprop- l-yl)benzo[b]thiophene. Reference Example 3

Methyl cyclopropyl ketone (0.79g) was added to a suspension of sodium hydride (60%, 0.38g) in dry ether. After 0.5 hours a solution of ethyl 2,3-dibromo-4-methylsulphenylthiophene-5- carboxylate (1.3g) in dry ether was added and the mixture heated at reflux for 1 hour. Hydrochloric acid (2M) was added and the organic phase washed (water), dried (magnesium sulphate) and evaporated to give 2,3-dibromo-5-(3-cyclopropyl-l,3-dioxoprop-l- yl)-4-methylsulphenylthiophene, NMR (CDCI3) δ 1.03(2H,m),

1.23(2H,m), 1.79(lH,m), 2.61(3H,s), 6.76(lH,s).

By proceeding in a similar manner the following compounds were prepared: methyl 2-(3-cyclopropyl-l,3-dioxoprop-l-yl)-3,4- dimethoxybenzo[b]thiophene-5-carboxylate, NMR (CDCI3) δ

1.02(2H,m), 1.23(2H,m), 1.81(lH,m), 3.98(3H,s), 4.05(6H,s), 6.76(lH,s), 7.56(lH,d), 7.88(lH,d), starting from dimethyl 4-chloro- 3-methoxybenzo[b]thiophene-2,5-dicarboxylate.

Reference Example 4

A solution of 4-(3-cyclopropyl-2-t-butyloxycarbonyl-l,3- dioxoprop-l-yl)-2,2-difluoro-l,3-benzodioxole (24.0g) and p- toluenesulphonic acid monohydrate (0.5g) was heated at reflux in dry toluene for 3.5 hours, the solution left overnight at room temperature and then evaporated. Ethyl acetate was added and the solution washed with water, dried (magnesium sulphate) and evaporated to give 4-(3-cyclopropyl-l,3-dioxoprop-l-yl)-2,2-difluoro- 1,3-benzodioxole (15.1g) as an orange oil. This was further purified by column chromatography on silica gel, eluting with ethyl acetate/cyclohexane and obtained as a solid m.p.46-47°C

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

4-(3-cyclopropyl- 1,3-dioxoprop- 1-yl)- l-ethyl-3- trifluoromethylpyrazole, NMR (CDCI3) δ 0.9(2H,m), l.l(2H,m), 1.45(3H,t), 1.65(lH,m), 4.15(2H,q), 6.0(lH,s), 7.9(lH,s),

16.0(lH,brs).

2-t-butyl-4-chloro-7-(3-cyclopropyl-l,3-dioxoprop-l- yl)benzoxazole as a yellow oil, NMR(CDC-3) ^δ l-l(2H,m), 1.25(2H,m), 1.55(9H,s), 1.85(lH,m), 6.7(lH,s), 7.4(lH,d), 7.95(lH,d), 16.3(lH,brs).

4-chloro-3-methoxy-2-methyl-7-(3-cyclopropyl-l,3-dioxoprop- l-yl)benzo[b]thiophene, NMR (CDC1₃) δ 1.03(2H,m), 1.23(2H,m),

1.71(lH,m), 2.5(3H,s), 3.86(3H,s), 6.4(lH,s), 7.37(lH,d), 7.7(lH,d), 16.34(lH,brs).

4-chloro-3-methoxy-7-(3-cyclopropyl-l,3-dioxoprop-l- yl)benzo[b]thiophene, NMR (CDCI3) δ 1.0(2H,m), 1.23(2H,m), 1.71(lH,m), 3.97(3H,s), 6.4(lH,s), 6.5(lH,s), 7.4(lH,d), 7.94(lH,d),

16.33(lH,brs).

7-bromo-4-(3-cyclopropyl-l,3-dioxoprop-l-yl)-l,3- benzoxathiole, NMR(CDCl3) δ 0.9(2H,m), 1.2(2H,m), 1.7(lH,m), 5.7(2H,s), 6.25(lH,s), 7.2(2H,m)

Reference Example 5

Carbon tetrachloride (5ml) was added to a vigorously stirred mixture of methanol (dry, 230ml), magnesium mrnings (1.77g) and t-butyl 3-cyclopropyl-3- oxopropanoate (13.32g). After 1 hour the solvent was evaporated and re-evaporated after addition of toluene.

The residue was suspended in acetonitrile (90ml) and a solution of 2,2-difluoro-l,3-benzodioxol-4-oyl-chloride (16.3g) in acetonitrile (90ml) added. The mixture was stirred overnight, a solution of hydrochloric acid (2M, 200ml) added and stirring resumed for 0.5 hours. Ethyl acetate was added and the extract washed with brine, dried (magnesium sulphate) and evaporated to give 4-(3- cyclopropyl-2-t-butyloxycarbonyl-l,3-dioxoprop-l-yl)-2,2-difluoro- 1,3-benzodioxole (24.2g) as a yellow oil.

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

4-(3-cyclopropyl-2-t-butyloxycarbonyl- 1,3-dioxoprop- 1-yl)- 1- ethyl-3-trifluoromethylpyrazole.

2-t-butyl-4-chloro-7 (3-cyclopropyl-2-t-butyloxycarbonyl- 1,3- dioxoprop-l-yl)benzoxazole. 4-chloro-3-methoxy-2-methyl-7-(3-cyclopropyl-2-t- butyloxycarbonyl-l,3-dioxoprop-l-yl)benzo[b]tbiophene.

4-chloro-3-methoxy-7-(3-cyclopropyl-2-t-butyloxycarbonyl-l,3- dioxoprop-l-yl)benzo[b]thiophene.

7-bromo-4-(3-cyclopropyl-2-t-butyloxycabronyl-l,3-dioxoprop- 1-yl)- 1,3-benzoxathiole.

Reference Example 6

2,2-Difluoro-l,3-benzodioxole-4-carboxylic acid (15.0g) was dissolved in 1,2-dichloroethane and N,N-dimethylformamide and thionyl chloride (10.6g) added. The mixture was heated under reflux for 1 hour and the solvent evaporated in vacuo. The residue was dissolved in toluene and re-evaporated to yield 2,2-difluoro-l,3- benzodioxole-4-carboxylic acid chloride (17.35g).

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

2,2-c fluoro-7-methylsulphenyl-l,3-benzodioxole-4-carboxylic acid chloride;

Reference Example 7

A mixture of l-ethyl-3-trifluoromethylpyrazole-4-carboxylic acid (1.7g) and oxalyl chloride (0.78ml) was stirred and heated at reflux with 1,2-dichloroethane (50ml) and N, N-dimethylformamide

(4 drops). After 1 hour the mixture was evaporated in vacuo to give l-ethyl-3-trifluoromethylpyrazole-4-carboxylic acid chloride (1.8g), used directly in the next stage.

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

2-t-butyl-4-chlorobenzoxazole-7-carboxylic acid chloride as an orange solid, used directly in the next stage.

2,3-dibromo-4-methylsulphenylthiophene-2-carboxylic acid chloride. 4-chloro-3-methoxy-2-methylbenzo[b]tbiophene-7-carboxylic acid chloride.

4-chloro-3-methoxybenzo[b]tbiophene-7-carboxylic acid chloride.

4-chloro-2-fluoro-3-methoxycarbonylbeπzoic acid chloride 7- bromo-l,3-benzoxathiole-4-carboxylic acid chloride.

Reference Example 8 Dimethyl 2,4-dichloro-isophthaloate (11.95g) and methyl thioglycolate (7.23g) was dissolved in N,N-dimethylformamide, and lithium hydroxide monohydrate (3.8 lg) added. The mixture was stirred at ambient temperature for 2 days, diluted with water and brought to pH 1 with hydrochloric acid. The solid was filtered, washed with boiling cyclohexane and dried by azeotropic removal of toluene to give dimethyl 4-chloro-3-hydroxybenzo[b]thiophene-2,5- dicarboxylate (13.44g) as a beige solid, m.p. 127-131°C.

Reference Example 9

2,4-Dichloro-3-methoxycarbonylbenzθylchloride (34.76g) was stirred and heated under reflux with methanol for 15 hours. After cooling, the solvent was evaporated and the residue recrystallised from cyclohexane to give dimethyl 2,4-dichloroisophthaloate (16.04g) as a beige solid, NMR (DMSO D₆) δ 3.87 (3H, s), 3.94

(3H, s), 7.74 (1H, d), 7.94 (1H, d).

Reference Example 10

2,4-Dichloro-3-methoxycarbonylbenzoic acid (32.37g) and thionyl chloride (100ml) was heated under reflux with stirring for 3 hours. The mixture was cooled and evaporated in vacuo, then re- evaporated after addition of toluene to give 2,4-dichloro-3- methoxycarbonylbenzoyl chloride (34.76g) as a dark brown oil. This was used in the next stage without purification.

Reference Example 11

To a stirred solution of dusopropylamine (22ml) in dry tetrahydrofuran (160ml) cooled to 0°C under an inert atmosphere was added n-butyl lithium (2.5M, 67ml) dropwise. The solution was stirred for 30 minutes at 0°C, then added to a solution of methyl 2,6- dichlorobenzoate (26.62g) in dry tetrahydrofuran (160ml) cooled to -78°C under an inert atmosphere. After 1.5 hours at this temperature the mixture was poured onto excess cardice and left to stand overnight. The solvent was evaporated in vacuo and the residue acidified with 2N hydrochloric acid. This was then extracted with ethyl acetate, dried over anhydrous magnesium sulphate and evaporated in vacuo to yield 2,4-dichloro-3-methoxycarbonylbenzoic acid (32.37g) as a solid, NMR (DMSO D₆) δ 3.93 (3H, s), 7.70 (1H, d), 7.91 (1H, d).

Reference Example 12 A mixture of dimethyl 4-chloro-3-hydroxybenzo[b]thiophene-

2,5-dicarboxylate (34.4g), cesium carbonate (40.9g) and tetraethylammonium iodide (1.47g) was heated overnight at 50°C with methyl iodide (35.5ml) in acetonitrile (500ml). After evaporation, ethyl acetate and water were added, the solid filtered off and the organic phase washed with water, dried (magnesium sulphate) and evaporated. The residue was purified by chromatography on silica gel eluting with ethyl acetate/cyclohexane to give dimethyl (4-chloro-3-methoxybenzo[b]thiophene-2,5- dicarboxylate (8.5g) as a yellow solid, m.p. 133-134.5°C

Reference Example 13

A solution of n-butyl lithium (88ml of 2.5M solution in hexane) was diluted with dry hexane under an inert atmosphere, cooled to 5°C and N,N,N',N'-tetramethylethylenedamine (33ml) in dry hexane added dropwise. Dry tetrahydrofuran was added at -35°C, the mixture cooled to -70°C and 2,2-difluoro-l,3-benzodioxole-4- carboxylic acid (20.2g) in dry tetrahydrofuran added during 1.5 hours keeping the temperature below -62°C After 20 hours at -75°C, dimethyldisulphide (25ml) was added during 30 minutes, and the mixture stirred at that temperature overnight and then at room temperature for 24 hours.

The mixture was poured into ice water, washed with ether and acidified to pHl with cone, hydrochloric acid. This was extracted with ether, the extracts washed with brine and dried over anhydrous magnesium sulphate. Evaporation of the solvent gave 2,2-difluoro-

7-methylsulphenyl-l,3-benzodioxole-4-carboxylic acid (17.75g) NMR (D₆ DMSO); δ 7.65 (1H, d), 7.25 (1H, d), 2.6 (3H, s).

2,2-Difluoro-l,3-benzodioxole-4-carboxylic acid is described in European Patent Publication No. 0333658.

Reference Example 14 n-Butyl lithium (101.6ml of a 2.5M solution in hexane) was added during 30 minutes to a stirred solution of 2,5-dichloro-l- (trimethylacetylamino)benzene (25.0g) in dry tetrahydrofuran (250ml) at -40°C, and the solution stirred at -20°C for 1.5 hours and poured onto cardice in dry tetrahydrofuran. The mixture was allowed to reach room temperature, 2M sodium hydroxide solution added and extracted with ethyl acetate. The aqueous solution was acidified (concentrated hydrochloric acid) and the precipitated solid collected and dried to give 2-t-butyl-4-chlorobenzoxazole-7- carboxylic acid (11.7g) m.p. 209-210°C.

Reference Example 15

To a stirred mixture of 2,5-dichloroaniline (15.0g), triethylamine (dry, 14.1ml) and 4-dimethylaminopyridine (0.45g) in dry dichloromethane (100ml) was added a solution of di-t- butyldicarbonate (22.2g) in dry dichloromethane. The mixture was stirred under nitrogen for 18 hours, and quenched by the addition of saturated ammonium chloride solution and extracted with dichloromethane. The extract was dried (magnesium sulphate), evaporated and purified by chromatography on silica gel eluting with cyclohexane to give 2,5-dichloro-l-

(trimethylacetylamino)benzene (12.2g) as a cream solid, used in the next stage without purification.

Reference Example 16 Ethyl l-ethyl-3-trifluoromethylpyrazole-4-carboxylate (2.17 g) was dissolved in ethanol and potassium hydroxide (1.06 g) in water was added. The reaction was stirred at room temperature overnight. Ethanol was removed under reduced pressure and the resulting residue partitioned between water and ether. The aqueous layer was separated, acidified with hydrochloric acid (2 M) and extracted with ether. The combined organic extracts were dried over anhydrous magnesium sulphate and evaporated in vacuo to give l-ethyl-3-trifluoromethylpyrazole-4-carboxylic acid as a white solid (1.86 g). NMR (CDC1₃) δ 1.45(3H.t), 4.20(2H,q), 7.95(lH,s). By proceeding in a similar manner the following compound was prepared:

2-t-butyl-4-methylsulphenylbenzoxazole-7-carboxylic acid, m.p. 203-204OQ

Reference Example 17

Ethyl 3-trifluoromethylpyrazole-4-carboxylate (5 g), potassium carbonate (3.48 g) and ethyl iodide (2.3 ml) in acetonitrile were heated at reflux overnight. After cooling, ethyl acetate and water were added and the organic phase separated. The aqueous layer was extracted with ethyl acetate and the combined organic extracts were dried (magnesium sulphate) and evaporated under reduced pressure to give a yellow oil which was purified by crystallisation in hexane to produce 4-ethoxycarbonyl-l-ethyl-3- trifluoromethylpyrazole as white crystals (3.65 g), Η NMR (CDCI3) δ 1.25(3H,t), 1.45(3H,t), 4.10(2H,q), 4.20(2H,q) 7.90(lH,s) ppm.

Reference Example 18

A solution of 2,3-dibromo-4-methylsulphenylthiophene-2- carboxylic acid chloride (3.3g) in dichloromethane (10ml) was treated with ethanol (12ml) and triethylamine (1.1ml) and stirred overnight. Evaporation gave a solid which was suspended in ether and washed with hydrochloric acid (2M) and water, and then re- evaporated. Recrystallisation from hexane/ethyl acetate gave ethyl 2,3-dibromo-4-methylsulphenylthiophene-2-carboxylate (1.7g) as a brown solid, NMR (CDCI3) δ 1.39(3H,t), 2.60(3H,s), 4.38(2H,q).

Reference Example 19 n-Butyllithium (14ml of a 2.5M solution in hexanes) was added to a solution of diisopropylamine (9.8ml) in dry tetrahydrofuran stirred under an inert atmosphere at -78°C. After 5 minutes, a solution of 2,3-dibromothiophene-5-carboxylic acid (5.0g) in tetrahydrofuran was added and the mixture stirred at -70°C for 15 minutes. Dimethyldisulphide (1.58ml) was then added and the mixture allowed to reach room temperature during 2 hours. Hydrochloric acid (2M) was added and the solution extracted (ethyl acetate). The extract was dried (magnesium sulphate) and evaporated to give 2,3-dibromo-4-methylsulphenylthiophene-5- carboxylic acid (3.0g) as a white solid, NMR (DMSO Dg) δ 2.67(3H,s). Reference Example 20

A mixture of 4-chloro-3-hydroxybenzo[b]thiophene-7- carboxylic acid (12.65g), casium carbonate (39.7g) and methyl iodide (28ml) was heated with tetrabutyl ammonium iodide (l.Og) in acetone (280ml) at 50°C for 3 days. After evaporation the residue was partitioned between water and ether, and the organic phase dried (magnesium sulphate) and evaporated. The aqueous phase was acidified (hydrochloric acid), extracted/ethyl acetate), dried (magnesium sulphate) and evaporated. The combined residues were purified by chromatography to give methyl 4-chloro-3- methoxybenzo[b]thiophene-7-carboxylate, m.p. 114.5-116°C, and methyl 4-chloro-3-methoxy-2-methylbenzo[b]thiophene-7- carboxylate, m.p. 88-92.5°C.

Reference Example 21

A mixture of 4-chloro-7-hydroxy-7-N-isobutylcarbamoyl-2- methoxycarbonylbenzo[b]thiophene (27.9g) and sodium hydroxide solution (3M,330ml) was heated under reflux for 24 hours. With stirring, hydrochloric acid (2M) was added cautiously to pH7 whilst maintaining the oilbath at 135-145°C. Concentrated hydrochloric acid was then added under the same conditions with evolution of gas. After an additional 24 hours stirring at this temperature, the cooled mixture was filtered and the solid washed (water) and dried (vacuum oven) to give 4-chloro-3-hydroxybenzo[b]thiophene-7- carboxylic acid (18.3g), NMR (DMSOD6) δ 6.66(lH,s), 7.46(lH,d), 7.91(lH,d), 10.2(lH,s).

Reference Example 22 A mixture of 4-chloro-2-fhιoro-3-methoxycarbonyl-N- isobutylbenzamide (29.6g), methyl thioglycolate (4ml) and potassium carbonate (12.2g) in acetonitrile was stirred under reflux conditions for 18 hours. The cooled mixture was concentrated to low volume and poured onto ice and hydrochloric acid. The precipitated solid was filtered, washed (water) and dried (vacuum oven) to give 4-chloro-3-hydroxy-7-isobutylcarbamoyl-2- methoxycarbonylbenzo[b]thiophene (27.9g), m.p. 163-169°C. Reference Example 23

To a solution of 4-chloro-2-fluoro-3-methoxycarbonylbenzoyl chloride (26.3g) in dichloromethane at 0°C was added dropwise a mixture of triethylamine (30ml) and isobutylamine (10.5ml). The mixture was stirred at room temperature for 18 hours, evaporated and ether added. The solution was worked with hydrochloric acid (2M), then with water, and dried (magnesium sulphate). After evaporation of the solvent there was obtained 4-chloro-2-fluoro-3- methoxycarbonyl-N-isobutylbenzamide (29.5g) as a red oil,

NMR(CDCl3) δ 0.91(6H,d), 1.83(lH,m), 3.24(2H,t), 3.9(3H,s), 6.57(lH,brs), 7.27(lH,d), 8.03(lH,t).

Reference Example 24 A suspension of methyl 4-chloro-3-methoxy-2- methylbenzo[b]thiophene carboxylate (0.87g) and lithium hydroxide monohydrate (0.13g) was stirred in a mixture of methanol and water for 24 hours. The mixture was poured onto ice and hydrochloric acid, the precipitated solid filtered and washed with water then with cyclohexane to give 4-chloro-3-methoxy-2-methylbenzo[b]thiophene-

7-carboxylic acid (0.54g) as a yellow solid, NMR (CDCI3) δ 2.40(3H,s), 3.80(3H,s), 7.30(lH,d), 7.89(lH,d).

By proceeding in a similar manner the following compounds were prepared: 4-chloro-3-methoxybenzo[b]thiophene-7-carboxylic acid as a beige solid, NMR (CDCI3) δ 3.90(3H,s), 6.46(lH,s), 7.31(lH,d), 7.93(lH,d).

7-bromo-l,3-benzoxathiole-4-carboxylic acid, m.p. 265-269°C.

Reference Example 25 n-Butyllithium (2.5M solution in hexanes, 17ml) was added dropwise to a solution of methanethiol (2.2g) in tetrahydrofuran at - 78°C under an inert atmosphere. After 0.5 hour at that temperature a solution of ethyl 2,4-dibromo-3-cbioromethoxy benzoate (16.7g) in tetrahydrofuran was added and the solution maintained at 078°C for 1.5 hours and then at ambient temperature for 24 hours. Ether and water were added and the organic phase dried (magnesium sulphate) and evaporated. Crystallisation from cyclohexane gave ethyl 7-bromo-l,3-benzoxathiole-4-carboxylate (5.7g), m.p. 75-77⁰C

Reference Example 26

A mixture of ethyl 2,4-dibromo-3-hydroxybenzoate (15g), anhydrous potassium carbonate (13.4g), potassium iodide (2.0g) and bromochloromethane (31g) was heated in N,N-dimethylformamide at 60°C for 20 hours. The cooled mixture was diluted with water and extracted (ether). The extract was washed (water), dried

(magnesium sulphate) and evaporated to give ethyl 2,4-dibromo-3- chloromethoxybenzoate (16.7g) as a yellow oil, NMR (CDCI3) δ 1.4(3H,t), 4.4(2H,q), 5.95(2H,s), 7.35(lH,d), 7.55(lH,d).

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 derivatives are 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 (e.g. 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, 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 appUcation 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 between 0.01kg and 5kg 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 between 0.01kg and 4.0kg, and preferably between 0.01kg and 2.0kg, 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 rion- 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 between

0.25kg and 5.0kg, and preferably between 0.5kg and 4.0kg 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 between 1.0kg and 20.0kg, and preferably between 5.0 and 10.0kg, 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 an agriculturally acceptable salt 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, adsorbent 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.

When desired, liquid compositions of the compound of formula I may be used in the form of self-emulsifying concentrates containing the active substances dissolved in the emulsifying agents or in solvents containing emulsifying agents compatible with the active substances, the simple addition of water to such concentrates producing 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, stabilisers, sequestering agents, anti-caking agents, colouring agents and corrosion inhibitors. These adjuvants may also serve as carriers or diluents. Unless otherwise specified, the following percentages are by weight. Preferred herbicidal compositions according to the present invention are aqueous suspension concentrates which comprise from 10 to 70% of one or more compounds of formula I, from 2 to 10% of surface-active agent, from 0.1 to 5% of thickener and from 15 to

87.9% of water; wettable powders which comprise from 10 to 90% of one or more compounds of formula I, from 2 to 10% of surface-active agent and from 8 to 88% of solid diluent or carrier; water soluble or water dispersible powders which comprise from 10 to 90% of one or more compounds of formula I, from 2 to 40% of sodium carbonate and from 0 to 88% of solid diluent; liquid water soluble concentrates which comprise from 5 to 50%, e.g. 10 to 30%, of one or more compounds of formula I, from 5 to 25% of surface-active agent and from 25 to 90%, e.g. 45 to 85%, of water miscible solvent, e.g. dimethylfoπnamide, or a mixture of water-miscible solvent and water; liquid emulsifiable suspension concentrates which comprise from 10 to 70% of one or more compounds of formula I, from 5 to 15% of surface-active agent, from 0.1 to 5% of thickener and from

10 to 84.9% of organic solvent; granules which comprise from 1 to 90%, e.g. 2 to 10% of one or more compounds of formula I, from 0.5 to 7%, e.g. 0.5 to 2%, of surface-active agent and from 3 to 98.5%, e.g. 88 to 97.5%, of granular carrier and emulsifiable concentrates which comprise 0.05 to 90%, and preferably from 1 to 60% of one or more compounds of formula I, from 0.01 to 10%, and preferably from 1 to 10%, of surface-active agent and from 9.99 to 99.94%, and preferably from 39 to 98.99%, of organic solvent.

Herbicidal compositions according to the present invention may also comprise the compounds of formula I in association with, and preferably homogeneously dispersed iri, 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- 1- methylemylan- no)-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 cypeπnethrin, and fungicides, e.g. carbamates, e.g. methyl N-(l-t-butyl-carbamoyl- benzimidazol-2- yl)carbamate, and triazoles e.g. l-(4-chloro-phenoxy)-3,3- dimethyl- l-( 1,2,4-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 utilized in the form of conventional derivatives, for example alkali metal and amine salts and esters.

According to a further feature of the present invention there is provided an article of manufacture comprising at least one of the isoxazole derivatives of formula I or, as is preferred, a herbicidal composition as hereinbefore described, and preferably a herbicidal concentrate which must be diluted before use, comprising at least one of the isoxazole derivatives of formula I within a container for the aforesaid derivative or derivatives of formula I, or a said herbicidal composition, and instructions physically associated with the aforesaid container setting out the manner in which the aforesaid derivative or derivatives of formula I or herbicidal composition contained therein is to be used to control the growth of weeds. The containers will normally be of the types conventionally used for the storage of chemical substances which are solid at normal ambient temperatures and herbicidal compositions particularly in the form of concentrates, for example cans and drums of metal, which may be internally lacquered, and plastics materials, bottles or glass and plastics materials and, when the contents of the container is a solid, for example granular, herbicidal compositions, boxes, for example of cardboard, plastics materials and metal, or sacks. The containers will normally be of sufficient capacity to contain amounts of the isoxazole derivative or herbicidal compositions sufficient to treat at least one acre of ground to control the growth of weeds therein but will not exceed a size which is convenient for conventional methods of handling. The instructions will be physically associated with the container, for example by being printed directly thereon or on a label or tag affixed thereto. The directions will normally indicate that the contents of the container, after dilution if necessary, are to be applied to control the growth of weeds at rates of application between 0.01kg and 20kg of active material per hectare in the manner and for the purposes hereinbefore described.

The following Examples illustrate herbicidal compositions according to the present invention:

EXAMPLE Cl A soluble concentrate is formed from : Active ingredient (compound 1) 20% w/v

Potassium hydroxide solution 33% w/v 10% v/v

Tetrahydrofurfuryl alcohol (THFA) 10% v/v Water to 100 volumes, by stirring THFA, active ingredient (compound 1) and 90% volume of water and slowly adding the potassium hydroxide solution until a steady pH 7-8 was obtained then making up to volume with water. Similar soluble concentrates may be prepared as described above by replacing the isoxazole (compound 1) with other compounds of formula I.

EXAMPLE C2 A wettable powder is formed from :

Active ingredient (compound 1) 50% w/w

Sodium dodecylbenzene sulphonate 3% w/w

Sodium lignosulphate 5% w/w

Sodium formaldehyde alkylnaphthalene sulphonate 2% w/w Microfine silicon dioxide 3% w/w and

China clay 37% w/w by blending the above ingredients together and grinding the mixture in an air jet mill.

Similar wettable powders may be prepared as described above by replacing the isoxazole (compound 1) with other compounds of formula I.

EXAMPLE C3

A water soluble powder is formed from :

Active ingredient (compound 1) 50% w/w

Sodium dodecylbenzenesulphonate 1% w/w

Microfine silicon dioxide 2% w/w

Sodium bicarbonate 47% w/w by mixing the above ingredients and grinding the above mixture in a hammer mill.

Similar water soluble powders may be prepared as described above by replacing the isoxazole (compound 1) with other compoimds of formula I.

Representative compounds of formula I 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 up to 4000g test compound per hectare (g/ha).

These solutions were applied from a standard laboratory herbicide sprayer delivering the equivalent of 290 litres of spray fluid per hectare.

b) Weed control : Pre-emergence

The seeds were sown in 70 mm square, 75 mm deep plastic pots in non-sterile soil . The quantities of seed per pot were as follows:-

Weed species Approx number of seeds/pot ϊ) Broad-leafed weeds

Abutilon theophrasti 10

Amaranthus retroflexus 20

Galium aparine 10

Ipomoea purpurea 10 Sinapis arvensis 15

Xanthium strumarium 2.

2) Grass weeds

Alopecurus myosuroides 15

Avena fatua 10 Echinochloa crus-galli 15

Setaria viridis 20.

3) Sedges

Cyperus esculentus 3.

Crop

1) Broad-leafed

Cotton 3

Soya 3.

2) grass Maize 2

Rice 6

Wheat 6. The compounds of the invention were applied to the soil surface, containing the seeds, as described in (a). A single pot of each crop and each weed was allocated to each treatment, with unsprayed controls and controls sprayed with acetone alone.

After treatment the pots were placed on capillary matting kept in a glass house, and watered overhead . Visual assessment of crop damage was made 20-24 days after spraying. The results were expressed as the percentage reduction in growth or damage to the crop or weeds, in comparison with the plants in the control pots.

c) Weed control : Post-emergence

The weeds and crops were sown directly into John Innes potting compost in 75 mm deep, 70 mm square pots except for Amaranthus which was pricked out at the seedling stage and transferred to the pots one week before spraying. The plants were then grown in the greenhouse until ready for spraying with the compounds used to treat the plants. The number of plants per pot were as follows :-

1) Broad leafed weeds

Weed species Number of plants per pot Growth stage

Abutilon theophrasti 3 1-2 leaves

Amaranthus retroflexus 4 1-2 leaves

Galium aparine 3 1^st whorl

Ipomoea purpurea 3 1-2 leaves

Sinapis arvensis 4 2 leaves

Xanthium strumarium 1 2-3 leaves.

2) Grass weeds

Weed species Number of plants per pot Growth stage

Alopecurus myosuroides 8-12 1-2 leaves

Avena fatua 12-18 1-2 leaves

Echinochloa crus-galli 4 2-3 leaves

Setaria viridis 15-25 1-2 leaves. 3) Sedge?

Weed species Number of plants per pόt Growth stage Cyperus esculentus 3 3 leaves.

1^ Broad leafed Crops Number of plants per pot Growth stage Cotton 2 l leaf Soya 2 2 leaves.

2^ Grass Crops Number of plants per pot Growth stage Maize 2 2-3 leaves Rice 4 2-3 leaves Wheat 5 2-3 leaves.

The compounds used to treat the plants were applied to the plants as described in (a). A single pot of each crop and weed species was allocated to each treatment, with unsprayed controls and controls sprayed with acetone alone.

After treatment the pots were placed on capillary matting in a glass house, and watered overhead once after 24 hours and then by controlled sub-irrigation. Visual assessment of crop damage and weed control was made 20-24 days after spraying. The results were expressed as the percentage reduction in growth or damage to the crop or weeds, in comparison with the plants in the control pots.

When applied either pre- or post- emergence at 4 Kg/ha or less, compounds 1 to 13 gave at least 90% control of one or more weed species.

Claims

1. An isoxazole of formula I:

(I) wherein:

Ar represents a monocyclic or fused bicyclic heterocyclic system Het having a non-pyridyl heterocyclic first ring and an optional second heterocyclic or carbocyclic ring, the second ring when present being fused to the first ring, the first ring having from

1 to 4 hetero ring atoms and from 4 to 7 total ring atoms, the first ring being aromatic or non-aromatic and being optionally substituted by from 1 to 4 R² groups which may be the same or different, the second ring being optionally substituted by from 1 to 4 R² groups which may be the same or different;

R represents the hydrogen atom or a group -C0₂R³; Rl represents:- a straight- or branched- chain alkyl group containing from one to six carbon atoms which is optionally substituted by one or more halogen atoms; or a cycloalkyl group containing from three to six carbon atoms optionally substituted by one or more groups selected from R⁴, -C0₂R⁴, -SR⁴, halogen and -OR⁴; R² represents:- a halogen atom, a straight- or branched- chain alkyl group containing from one to six carbon atoms which is substituted by a group -OR⁴; or a group selected from -OH, R⁴, -SR⁵, -SOR⁵, -S0₂R⁵, -O-SC^R⁵, -C0₂R⁴, -COR⁴, -OR⁵, -NR6R7 -N(R8)S0₂R⁵, nitro, cyano, -0(CH₂)_m-OR⁴, -(-CR⁹Rl0-)_t-S(O)pR⁵ and -NRURI²; when the first and/or second ring of Het is non-aromatic, then R² may also represent =0, =S, cyclic ketal or cyclic thioketal;

R3 and R⁴, which may be the same or different, each represent a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to six carbon atoms which is optionally substituted by one or more halogen atoms;

R⁵ represents a group R⁴, or phenyl optionally substituted by from one to five groups which may be the same or different selected from halogen, R⁴, -C0₂R⁴, -COR⁴, -OR⁴, nitro, cyano and -0(CH₂)_m-OR⁴;

R6 and R⁷, which may be the same or different, each represent the hydrogen atom or a straight- or branched- chain alkyl group containing from one to six carbon atoms which is optionally substituted by one or more halogen atoms; m represents an integer from one to three;

R⁸ represents the hydrogen atom; a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to six carbon atoms optionally substituted by one or more halogen atoms; a cycloalkyl group containing from three to six carbon atoms; or phenyl optionally substituted by from one to five groups R² which may be the same or different;

R⁹ and RlO, which may be the same or different, each represents: the hydrogen atom; a straight- or branched-chain alkyl group containing up to 6 carbon atoms which is optionally substituted by one or more halogen atoms; or phenyl optionally substituted by from one to five groups which may be the same or different selected from halogen, R⁴, -C0₂R⁴, -COR⁴, -OR⁴, nitro, cyano and -0(CH₂)_m-OR⁴; p is zero, 1 or 2; t represents an integer from one to three;

R¹¹ represents -COR⁴ or -C0₂R⁴;

Rl2 represents:- the hydrogen atom; a straight- or branched- chain alkyl group containing up to six carbon atoms optionally substituted by one or more halogen atoms; or a cycloalkyl group containing from three to six carbon atoms; or an agriculturally acceptable salt thereof.

2. A compound according to claim 1 in which Ar represents optionally substituted 1,3-benzodioxole, benzo[b]thiophene, 1,3-benzoxathiole, 3,3-dioxo-l,3-benzoxathiole or benzoxazole.

3. A compound according to claim 1 in which Ar represents optionally substituted pyrazolyl or thienyl.

4. A compound according to claim 1, 2 or 3 in which Ar represents a group Het which is optionally substituted by from one to three groups R².

5. A compound according to any one of claims 1 to 4 in which R represents hydrogen.

6. A compound acccording to any one of claims 1 to 5 in which Rl represents a straight- or branched- chain alkyl group containing up to four carbon atoms; or a cyclopropyl group optionally substituted by a group R⁴.

7. A compound according to any one of claims 1 to 6 in which R² represents a halogen atom or a group selected from -SR⁵, -SOR⁵, -S0₂R⁵, -CH₂S(0)_pR⁵, -C0₂R⁴ R⁵ and -OR⁵.

8. A compound according to claim 1 which is: 4-cyclopropylcarbonyl-5-(2,2-difluoro-l,3-benzodioxol-4- yl)isoxazole;

5-(2-t-butyl-4-chlorobenzoxazol-7-yl)-4-cyclopropyl- carbonylisoxazole;

4-cyclopropylcarbonyl-5-(7-methylsulphenyl-l,3-benzodioxol- 4-yl)isoxazole;

4-cyclopropylcarbonyl-5-(7-methylsulphinyl-l,3-benzodioxol-4- yl)isoxazole; 4-cyclopropylcarbonyl-5-(7-methylsulphonyl- 1,3-benzodioxol-

4-yl)isoxazole;

4-cyclopropylcarbonyl-5-(l-ethyl-3-trifluoromethyl-pyrazol-4- yl)isoxazole;

4-cyclopropylcarbonyl-5-(4,5-dibromo-3-methylsulphenylthien- 2-yl)isoxazole;

4-cyclopropylcarbonyl-5-(3,4-dimethoxy-5- methoxycarbonylbenzo[b]thien-2-yl)isoxazole;

4-cyclopropylcarbonyl-5-(3,4-dimethoxy- 1, l-dioxo-5- methoxycarbonylbenzo[b]thien-2-yl)isoxazole;

5-(4-chloro-3-methoxy-2-methylbenzo[b]thien-7-yl)-4- cyclopropylcarbonylisoxazole;

5-(4-chloro-l,l-dioxo-3-methoxybenzo[b]thien-7-yl)-4- cyclopropylcarbonylisoxazole;

5-(7-bromo-l,3-benzoxathiol-4-yl)-4- cyclopropylcarbonylisoxazole; or

5-(7-bromo-3,3-dioxo-l,3-benzoxathiol-4-yl)-4- cyclopropylcarbonylisoxazole.

9. A herbicidal composition comprising an effective amount of a compound according to any one of claims 1 to 8 or an agriculturally acceptable salt thereof in association with an agriculturally acceptable diluent or carrier and/or surface active agent.

10. A method for the control of weeds at a locus which comprises applying to said locus an effective amount of a compound according to any one of claims 1 to 8 or an agriculturally acceptable salt thereof.

11. A process for the preparation of an isoxazole according to claim 1 which comprises:

(a) the metallation of a compound of formula (II):

<π) wherein R and Ar are as defined in claim 1 and X is a halogen atom, followed by reaction of the compound thus obtained with an acid chloride of formula R^COCl, wherein R is as defined in claim 1;

(b) where R represents hydrogen, reacting a compound of formula (HI):

(III) wherein Ar and Rl are as defined in claim 1 and L is a leaving group, with a salt of hydroxylamine; (c) where R represents hydrogen, reacting a compound of formula (IV):

O Ar (IV) wherein Ar is as defined in claim 1 and Y represents a carboxy group, a reactive derivative thereof or a cyano group, with an organometallic reagent of formula Rl-M wherein Rl is as defined in claim 1 and M represents an alkali metal, a metal bonded to one or more ligands, or a Grignard group;

(d) where R represents a group -C0₂R³, reacting a compound of formula (V):

O P

(V) wherein Ar and Rl are as defined in claim 1 and P is a leaving group, with a compound of formula R³0₂CC(X) =NOH wherein R³ is as defined and X is a halogen atom;

(e) where R represents a group -C0₂R³, reacting a compound of formula (VI):

wherein Ar and Rl are as defined in claim 1, with a compound of formula R³0₂CC(X) = NOH wherein R³ is as defined in claim 1 and X is as defined above;

(f) where R represents -C0₂R³, reacting the salt of a compound of formula (VII): O O

wherein Ar and Rl are as defined in claim 1 with a compound of formula R³0₂CC(X)=NOH wherein R³ is as defined in claim 1 and X are as defined above; (g) where R² represents -SOR⁵ or -S0₂R⁵, oxidising the sulphur atom of the corresponding compound of formula (I) in which R² represents -SR⁵ or -SOR⁵;

(h) where a ring member of the group Het is -SO- or -S0₂-, oxidising the ring sulphur atom of the corresponding compound of formula (I); optionally followed by the conversion of the compound thus obtained into an agriculturally acceptable salt thereof.