Field of the invention

This invention relates to new phenyloxoacetic acid derivatives which have fungicidal activity and are useful also in the preparation of fungicidally active alkyl 2-aryl-3-alkoxy-2-propenoate derivatives.

Prior Art

In EP 178826, there are disclosed certain alkyl 2-aryl- 3-alkoxy-2-propenoate derivatives having fungicidal activity. One method of preparation which is described is via the corresponding oxoacetate. In EP 254426, there are disclosed compounds analogous to those in EP 178826, in which the methylene group of the propenoate moiety is replaced by an imino group. These compounds can also be prepared via the corresponding oxoacetate.

Description of the Invention

We have now found new phenyloxoacetic acid derivatives which have fungicidal activity and which can also be used as intermediates to certain fungicidally active alkyl 2-aryl-3-alkoxy-2-propenoate derivatives.

According to the invention there is provided a compound of formula I

wherein X is alkyl, alkenyl, alkynyl or alkoxy, each of which is

optionally substituted, aryl, halogen or nitro. R ¹ is hydrogen or alkyl, and a) R ² and R ³ , which may be the same or different, are alkyl, alkenyl, alkynyl or cycloalkyl, each of which is optionally substituted, hydrogen, fluoro, cyano or aryl, and R ⁴ is aryl or the group R ⁵ CO, or b) R ² and R ³ together can form an oxo group, and

R ⁴ is alkyl, alkenyl, alkynyl or cycloalkyl, each of which is optionally substituted, or aryl;

R ⁵ is R ⁶ O _n or optionally substituted amino; R ⁶ is alkyl, alkenyl, alkynyl or cycloalkyl, each of which is optionally substituted, or aryl; n is 0 or 1; and is 0 to 4, with the proviso that when m is 1, R ¹ , R ² and R ³ are hydrogen, and R ⁴ is phenyl, X is not methyl in the 3-position.

The compounds of formula I where R ¹ is hydrogen can be obtained by reacting benzo[b]thiophene-2,3-dione with a compound of formula II

R ³ _A I R ⁴ -C-Z (II)

where Z is a leaving group, e.g. halogen, generally under basic conditions.

The compound of formula I so obtained can then be esterified in conventional manner to give a compound of formula I where R ¹ is alkyl, preferably methyl.

The compounds of formula I where R ¹ is alkyl, are useful as intermediates in the preparation of compounds of formula la

R ² in which Z is N or CH and R ¹ and R ¹⁰ are alkyl, preferably methyl. These compounds have fungicidal activity. Compounds of this type are disclosed, for example in our EP 299 694.

Certain compounds of formula la are novel and the invention also includes the novel compounds of this type. In particular compounds where R ⁴ is the group R ⁵ CO are novel. However certain other individual compounds may also be novel and the invention also includes these.

The conversion of the compound of formula I to compounds of formula la, can be carried out in known manner. For example, where Z is CH, there can be used the method as described in EP 178 826, in which the compound of formula I is reacted with a phosphorane derived from a phosphorus salt of formula

Ph ₃ P ⁺ CH ₂ OR ¹⁰ Hal ^" under basic conditions. When Z is N, there can be used the method as described in EP 254 426, in which the compound of formula I is reacted with a substituted hydroxylamine of formula, R ¹⁰ ONH ₂

As stated above the compounds of formula la have fungicidal activity. Compounds of formula I, especially those where R ¹ is hydrogen, also generally have activity as fungicides. This activity manifests itself especially against fungal diseases of plants, e.g. mildews and particularly cereal powdery mildew (Ervsiphe graminis) ,

vine downy mildew (Plasmopara viticola) , rice blast (Pyricularia oryzae) , cereal eyespot (Pseudocercosporella herpotrichoides) , rice sheath blight (Pellicularia sasakii) , grey mould (Botrytis cinerea) , damping off (Rhizoctonia solani) , wheat brown rust (Puccinia. recondita) , potato blight (Phytophthora infestans) and apple scab (Venturia inaequalis) . Other fungi against which the compounds may be active include other powdery mildews, other rusts, and general pathogens of Deuteromycete, Ascomycete, Phycomycete and Basidiomycete origin.

In the compounds of the invention, alkyl groups are preferably of 1 to 4 carbon atoms, especially methyl or ethyl. Alkenyl, alkynyl and cycloalkyl groups are generally of three to nine carbon atoms. Substituents, when present on any alkyl, alkenyl, alkynyl or cycloalkyl group, include halogen, alkoxy (e.g. of 1 to 4 carbon atoms) , haloalkoxy (e.g. difluoromethoxy) hydroxy, alkylthio, nitro, optionally substituted amino, carboxy, alkoxycarbonyl, cyano, acyloxy and aryl. Aryl groups are usually phenyl, optionally substituted, e.g. by halogen, optionally substituted alkyl or alkoxy, aryl, aryloxy, nitro, amino, COOH, COOR ² , CN, CONR ² R ² or S(0) _p R ² (p - 0, 1 or 2) . In some cases two substituents, together with the phenyl to which they are attached, can form a fused ring which itself can be optionally substituted as for phenyl. The terms heteroaryl includes groups such as thienyl, furyl and pyridyl, which themselves may be substituted, e.g. as for phenyl. The term "acyl" includes the residue of sulphonic and phosphorus containing acids as well as carboxylic acids. Amino groups may be substituted, e.g. by one or two alkyl groups or two substituents can form a ring, e.g. to form a morpholino or piperidino ring.

Particularly preferred compounds are those where R ² and R ³ are hydrogen and R ⁴ is optionally substituted phenyl. Especially preferred substituents on the phenyl are alkyl, alkoxy, halo, trifluoromethyl or cyano.

The invention is illustrated in the following Examples. Structures of isolated novel compounds were confirmed by elemental and/or other appropriate analyses. Temperatures are in °C.

Example 1 A mixture of benzo[b]thiophene-2,3-dione (5.0 g) and aqueous sodium hydroxide (2.44 g in 50 ml water) was heated under reflux for one hour. To the resulting solution at 50°, was added 2,6-difluorobenzyl chloride (4.95 g) and the mixture refluxed for a further 2 hours and allowed to cool. It was acidified to pH 1, extracted with ether and the extract dried and evaporated. The residue was recrystallised from diisopropyl ether to give 2-[2-(2,6-difluorobenzylthio)phenyl]-2-oxoacetic acid, mp 120-2°. (Compound la)

In a similar manner the following compounds were obtained

mp ( ° )

132-4

131-2

121-2

123-5

118-120 102-3

Compound No R^ R ^H mp(°)

* = not isolated

Example 2

To a solution of compound la (7.0 g) in dichloromethane (100 ml) was added triethylamine (2.5 g) , followed by dropwise addition of methyl chloroformate (2.25 g) . The mixture was heated under reflux for 0.5 hours, cooled, washed with aqueous sodium hydrogen carbonate, dried and evaporated. The residue was recrystallised from diisopropyl ether to give methyl 2-[2-(2,6-difluorobenzyl- thio)phenyl]-2-oxoacetate, mp 53-5°. (Compound 2a)

In a similar manner the following compounds were obtained

A solution of compound 2a (1.8 g) in ether (20 ml) was added dropwise to a mixture of potassium tert-butoxide (0.98 g) and a suspension of (methoxymethyl)triphenyl- phosphonium chloride (3.0 g) in ether (50 ml), which had been stirred for 45 minutes. The reaction mixture was stirred for 4 hours, washed with water, dried and evaporated. The residue was dissolved in dichloromethane, filtered through silica gel and evaporated. The residue was recrystallised from diisopropyl ether to give methyl (E)-3-methoxy-2-[2-(2,6-difluorobenzylthio)phenyl]prop- 2-enoate, p 100-1°. (Compound 3a)

In a similar manner, the following compounds were obtained. In most cases the compound was isolated in the form of its E-isomer. Occasionally, the Z-isomer was also isolated (indicated by a melting point in the appropriate column in the table below) . Separation of the isomers was achieved by silica gel column chromatography.

Example 4

A solution of Compound 2a (2.75 g) and O-methylhydroxyl- amine hydrochloride (0.78 g) in methanol (100 ml) was stirred and heated under reflux for 16 hours. The mixture was evaporated and partitioned between ether and dilute aqueous sodium bicarbonate. The organic phase was dried and evaporated. The residue was purified by silica gel column chromatography using ethyl acetate/ hexane (4:1) as eluent and recrystallised from diisopropyl ether to give methyl (E)-2-(2,6-difluorobenzyl) (methoxyimino)acetate, m.p. 105-6° (Compound 4a) .

In a similar manner, the following compounds were obtained:

Test Example

Compounds are assessed for activity against one or more of the following:

Plasmopara viticola: vine downy mildew (PV) Erysiphe crraminis: barley powdery mildew (EG) Pyricularia oryzae: rice blast (PO) Botrvtis cinerea: grey mould of tomato (BC) Venturia inaequalis: apple scab (VI) Leptosphaeria nodoru : glume blotch (LN)

Aqueous solutions or dispersions of the compounds at the desired concentration, including a wetting agent, were applied by spray or by drenching the stem base of the test plants. These plants were then inoculated with appropriate test pathogens and kept under controlled environment conditions suitable for maintaining plant growth and development of the disease. After an appropriate time, the degree of infection of the leaf surface was visually estimated. Compounds were considered active if they gave greater than 50% control of the disease at a concentration of 500 ppm (w/v) or less.

Activities were demonstrated as follows (+ = active) .

Compound PV PO BC VI EG LN

No la + lb + + lc + le +

If + lj + lp + +

Is + + +

IX + lad + lag + lak +

2a + +

2d +

2e +

2f + 2g + + +

2j +

2k +

21

2m

2n

2o +

2p +

2r +

2t +

2V +

2w +

2x + +

2y +

2z

2aa

Compound PV PO BC VI EG LN

2ab + + +

2ac +

2ad + 2ae + +

2af + +

2ag +

2ah +

2ai + + 2aj +

2ak +

2am +