AP276A - Fungicides - Google Patents

Abstract

Fungicidal compounds having formula (i): in which d and e are independently h or f; x and y are o or s; r1 to r4 have various specified values; a and b are independently h, iodo, nitro, cyano, c1-4 alkoxycarbonyl, c1-4 alkoxy (c1-4)alkyl, c1-4 alkylthio(c1-4)-alkyl, formyl, c1-4 alkylthio, halo(c1-4)alkylthio, halo(c1-4)alkoxy, c1-4alkylcarbonyl, -cr5=nor6 (where r5 and r6 are independently h or c1-4 alkyl), c2-4 alkenyl or c2-4 alkynyl, provided that a and b are not both h.

Description

FUNGICIDES

This invention relates to novel fungicidal acylaminobenzamides, to processes for preparing them, to fungicidal compositions containing them and to methods of using them to combat fungi, especially fungal infections of plants.

Acknowledgement is made of UK Application No. 42454/77 from which US Patent No. 4282218, for example, claims priority and of EP-A-0127990. The former describes acylanilides which have antiandrogenic properties and the latter describes aniline derivatives which have fungicidal properties.

According to the present invention there is provided a compound of the formula (I), in which A and B are independently H, iodo, nitro, cyano, alkoxycarbonyl, alkoxy(C^ ^)alkyl, alkylthio(Cj palkyl, formyl,

Cj , alkylthio, halo(Cj ^)alkylthio, halo(Cj ^)alkoxy, Cj^alkylcarbonyl, -CR =N0r6 (where R^ and are independently B or Cj alkyl), alkenyl or C« , alkynyl, provided that A and B are not both H; D and E are

2 independently H or fluoro; R is H, alkyl or Cj alkoxy; R is Cj alkyl, alkoxy or optionally substituted phenyl, or R^ and R^ together with the nitrogen atom to which they are attached join to form a morpholine, piperidine, pyrrolidine or azetidine ring which is optionally substituted with * alkyl; R^ is H; is trichloromethyl, C₂ θ alkyl (optionally substituted with halogen, C, _Q alkoxy or R'S(O) in which R' is Cj alkyl, alkenyl or C₂ alkynyl and n is 0, 1 or 2), cyclopropyl (optionally substituted with halogen or alkyl), C₂ θ alkenyl, C₂_g alkynyl or C₂_g alkoxy (each of which is optionally substituted with halogen), mono- or di(C. ,)alkylamino or the group, RON=C(CN) in which R

4 is Cj alkyl, or R and R together with the group C(O)N to which they are attached join to form an azetidin-2-one ring which is optionally substituted with halogen or alkyl; and X and Y are independently oxygen or sulphur.

Alkyl groups and the alkyl moiety of other alkyl-containing groups can be in the form of straight or branched chains. Examples are methyl, ethyl, propyl (n-and iso-propyl), butyl (η-, sec, iso- and t-butyl),

1.1- dimethylpropyl and 1,1-dimethylbutyl. Alkenyl and alkynyl groups can also be in the form of straight or branched chains. Examples are

1.1- dimethylbut-3-enyl and 1,l-dimethylprop-2-ynyl.

A suitable alkyl group for R is R(CH.j)₂C, where R is halo, Cj alkyl or Cj alkoxy, and especially the group F(CH₃)₂C. Another suitable alkyl

APOOO 27 6

8 9 8 9 group for R is F(R )(R )C, where R and R are independently H, alkyl or halo(C, ,) alkyl.

1-4

Halogen includes fluorine, chlorine and bromine.

Optional substituents of phenyl include: halogen, alkyl (for
example,	methyl)	, alkoxy (for exampl	e, methoxy), C^	alkylthio (for
example ,	methylthio), trifluoromethyl, trifluoromethoxy,	nitro, cyano, C^
alkoxycarbonyl,	amino and mono- and di(C^	4)alkylamino.
In one aspect the invention provides	a compound of	the formula (I) in
which A is iodo,	cyano,	nitro, alkoxycarbonyl,	Cl-4	alkylcarbonyl,
c!.4 alkoxy(C14	)alkyl,	C3 alkylthio, formyl,	4 alkylthio(C 4)alkyl
or -CH=NOR (where R is	C1_4 alkyl); R1 D and E are H; R	and R are	alkyl (especially
methyl or	ethyl)	: R3. B,	‘ iS C2-6	alkyl	optionally
substituted with halogen	or C^ 4 alkoxy;	and X and	Y are	both oxygen.
The	invention is illustrated by the	compounds	listed in Table I which
follows .	These	compound	s have the formula (I) in which 1	12 4 R , R , R , A and B
have the	values	shown in	the table. R ,	D and E are Η, ,	and X and Y are 0.
			TABLE I
Compound	R1	R2	R4	A	B	mpt (°C)
No
1	CH3	ch3	(CH3)3c	I	H	228.5-230.5
2	ch3	ch3	ch3ch9(ch3)2c	I	H
3	CH3	ch3	C1(CH3)2C	I	H
4	C„3	C„3	Br(CH3)2C	I	H
5	CH3	ch3	f(ch3)2c	I	H	165.5-168
6	CH3	ch3	CH3O(CH3)7C	I	H
7	C„3	ch3ch2	(CH3)3c	I	H
8	C„3	ch,ch7	CH^CH,(CH,)?C	I	H
9	c„3	CH^CH?	ckch3)2c	I	H
10	c„3	ch3ch?	Br(CH3)2C	I	H
11	CH3	ch^ch?	F(CH3)2c	I	H
12	C„3	CH^CH,	CH^O(CH?)?C	I	H
13	C„3	CH3	(CH3)3c	CN	H	145-148.5
14	C„3	C„3	F(ch3)2c	CN	H
15	C„3	CH3	(ch3)3c	no2	H	189-194

AP000276

- 3 TABLE I (Continued)

Compound No	R1	R2	R4	A	B	mpt (°C)
16	ch3	CH3	(CH3)3C	COOCH3	H	260 (decomp)
17	ch3	CH3	(CH3)3C	C0CH3	H
18	ch3	CH3	(CH3)3c	ch2och3	H
19	ch3	CH3	(ch3)3c	sch3	H	★
20	ch3	CH3	F(CH3)2C	C00CH3	H
21	ch3	ch3	F(CH3)2C	C0CH3	H
22	ch3	CH3	F(CH3)2C	ch2och3	H
23	ch3	CH3	F(CH3)2c	sch3	H	*
24	ch3	CH3	(ch3)3c	CHO	H
25	ch3	CH3	(ch3)3c	CH^SCH^	H
26	ch3	CH3	(ch3)3c	ch=noch3	H
27	CH3	CH3	F(CH3)2c	SCF3	H	*
28	CH3	CH3	(ch3)3c	cooch2ch^	H	208-209
29	CH3	CH3	(ch3)3c	CHO	H	186-187
30	ch3	ch3	F(CH3CH2)?C	I	H	143-145
31	ch3	CH3	F(CH3)(CH3CH?)C	I	H	146-147
32	ch3	CH3	F(FCH2)(CH3)C	I	H	140-144
33	ch3	ch3	F(CH3)2C	-CeCH	H	HO(decoop)
34	ch3	ch3	F(CH3)2C	-HC=CH2	H	164-165
35	CH3	ch3	(CH3)3C	-C«CH	H	130(decomp)

♦Compound No. 19 !H NMR (270MHz; CDCK) δ 1.33(9H,s),	2.5<j(3H,s),	2.85(3H,s),	3.10(3H,s)
7.13(2H,d), 7.40(lH,s), 7.74(lH,s) ppm.
♦Compound No. 23
H NMR (270MHz; CDCl-j) δ 1.68(6H,d),	2.50(3H,s),	2.85(3H,s),	3.12(3H,s)
7.18(lH,d), 7.25(lH,dd), 7.72(lH,d),	8.15(lH,bs)	ppm.
♦Compound No. 27
XH NMR (270MHz; CDCl.j) δ 1.68(6H,d),	2.87(3H,s),	3.15(3H,s),	7.35(lH,d)
7.85(lH,dd), 7.95(lH,s), 8.22(lH,6s)	ppm.
The compounds of the invention	can be made by, for example, the

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- 4 1 2 methods illustrated in Schemes 1 and 2. Throughout these Schemes R , R ,

R , A, B, D and E are as defined before.

In Scheme 1, compounds of formula (II) vhere A is for example cyano, or alkylthio, can be prepared by reacting iodo compounds of formula (IX) vith a transition metal salt, for example cuprous cyanide, or cuprous methanethiolate, in a suitable solvent such as Ν,Ν-dimethylformamide or dimethylsulphoxide.

Iodo compounds of formula (IX) can be made from anilines of formula (VIII), by treatment vith nitrous acid (generated for example from sodium nitrite and sulphuric acid) and an iodide source such as potassium iodide.

Anilines of formula (VIII) can be made from compounds of formula (VII), vhere P is a protecting group. For example, vhen P is a trifluoroacetyl group, it can be removed by treatment of compounds of formula (VII) vith a base in a hydroxylic solvent, such as potassium carbonate in methanol.

Compounds of formula (VII) can be prepared from anilines of formula 4 (VI) by reaction vith an acid chloride R COCI in a suitable organic solvent such as methylene chloride in the presence of a base such as a tertiary amine (for example triethylamine) or an alkali metal carbonate or hydroxide (for example sodium carbonate or sodium hydroxide).

Anilines of formula (VI) can be prepared from nitro compounds of formula (V), by reduction using standard methods, such as hydrogenation over a precious metal catalyst (for example palladium on charcoal) in a suitable solvent (for example ethyl acetate) or iron, or stannous chloride, in hydrochloric acid.

Nitro amides of formula (V) can be made from nitro acids of formula (IV), by treatment first vith a standard reagent such as thionyl chloride or oxalyl chloride to give the acid chloride, vhich is then reacted vith an 1 2 amine R R NH in a suitable solvent, such as methylene chloride, in the presence of a base such as a tertiary amine (for example triethylamine), or an alkali metal carbonate or hydroxide (for example potassium carbonate, or sodium hydroxide).

Nitro acids of formula (IV) can be made from compounds of formula (III) by protection of the amino group, vith a protecting group P, such as tri fluoroacetyl, by reaction vith trifluoroacetic anhydride.

In Scheme 2, compounds of formula (II) can be prepared from amino amides of formula (XIX) by reaction vith an acid chloride R C0C1 in a suitable organic solvent such as dichloromethane in the presence of a base

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- 5 such as a tertiary amine (for example triethylamine) or an alkali metal carbonate or hydroxide (for example sodium carbonate or sodium hydroxide).

Amino amides of formula (XIX) can be prepared from nitro compounds of formula (XXVII) by reduction using standard methods, such as hydrogenation over a precious metal catalyst (for example palladium on charcoal) in a suitable solvent (for example ethyl acetate) or iron, or stannous chloride in hydrochloric acid.

The route described in Scheme 2 is particularly useful for preparing compounds of formula (II) vhere A is iodo, C₂_^ alken-l-yl or C₂_4 alkyn-l-yl. In the case vhere A is C₂ alken-l-yl or C₂ alkyn-l-yl, the nitro compounds of formula (XXVII) can be prepared from iodides of formula (XXVI) by reaction with a C₂ ^alkyne or a 1-tri-n-butylstannyl-(C₂ ^)alkene in a suitable solvent (for example Ν,Ν-dimethylformamide or acetonitrile) in the presence of a catalyst (for example bis (triphenylphosphine)palladium-II-dichloride) optionally in the presence of a copper I salt (for example cuprous iodide). Vhere A is ethynyl, the C₂_₄alkyne used is trimethylsilylethyne, and the trimethylsilyl group may be removed in a subsequent step by treatment with potassium carbonate in a suitable solvent such as methanol. In the case vhere A is iodo, the iodides of formula (XXVI) are used directly as the nitro compounds of formula (XXVII).

Iodides of formula (XXVI) can be prepared from nitro acids of formula (XXV) by treatment first vith a standard reagent such as thionyl chloride or oxalyl chloride to give the acid chloride, vhich is then reacted vith an 1 2 amine R R NH in a suitable solvent, such as dichloromethane, in the presence of a base such as a tertiary amine (for example triethylamine), or an alkali metal carbonate or hydroxide (for example potassium carbonate or sodium hydroxide).

Nitro acids of formula (XXV) can be prepared from anilines of formula (III) by treatment vith nitrous acid (generated for example from sodium nitrite and sulphuric acid) and an iodide source such as potassium iodide.

The compounds of the invention may also be prepared using methods and techniques described in EP-A-0381330 and in UK Applications Nos. 9016577.0, 9016580.4 and 9016582.0 and applications claiming priority therefrom, the contents of vhich are incorporated herein by reference.

In a further aspect, the invention provides processes as herein described for preparing the compounds of the invention, including the process described in EP-A-0381330 vhen used for preparing the invention

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- 6 compounds. In this latter process, compounds of the invention are prepared:

a) when X and Y are both oxygen and R is H,

i) by reacting a compound of general formula (X), with an acid chloride R COCl in a suitable organic solvent in the presence of a base; or ii) by reacting a compound of general formula (XI), with an amine 1 2

R R NH in a suitable organic solvent in the presence of a base or 1 2 excess R R NH; or iii) by reacting a compound of general formula (XII), with a compound 4 of general formula R -CO-NHj and a base; or

4

b) when X and Y are both oxygen and R and R together vith the group C(O)N form a ring of the formula (XIII),

i) by treating a compound of general formula (XIV), vith a base in a tvo-phase system consisting of an organic solvent and water in the presence of a phase-transfer catalyst; or

4

c) when X and Y are both oxygen, R is H and R is the group (XV),

i) by treating a compound of general formula (XVI), vith a fluoride transfer reagent in a suitable solvent; or

4

d) when X and Y are both oxygen, R is H and R is the group (XVII),

i) by treating a compound of general formula (XVIII), vith a fluorinating agent in a suitable solvent; or

e) when X is oxygen or sulphur, Y is sulphur and R is H,

i) by treating a compound of general formula (II), vith a thionation reagent in a suitable solvent to form either a compound of general formula (I) in vhich X is oxygen, Y is sulphur and R³ is hydrogen or a mixture of a compound of general formula (I) in vhich X is 3 oxygen, Y is sulphur and R is hydrogen and a compound of general 3 formula (I) in vhich X and Y are both sulphur and R is hydrogen; or

f) when X is sulphur, Y is oxygen and R is H,

i) by reacting an isothiocyanate of general formula (XXI), vith an

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- 7 4 4 organometallic reagent R Li or R Mg-hal in a suitable solvent at a temperature between -78^eC and +25^eC; or

2 ii) by reacting an acid chloride (XXII), vith an amine R R NH in the presence of a base; or

4

g) vhen X and Y are both oxygen, R is H and R is the group (XXIII),

i) by reacting a compound of general formula (XXIV), vith a halide

R³³-hal in the presence of a base in a suitable solvent;

4 wherein A, B, D, E, R , R and R (except where otherwise stated) have the meanings given in claim 1, R^ and R are independently H, C. , alkyl or

9 11 halogen, R and R are independently H, alkyl or halo(Cj ^)alkyl, R is alkyl, X' is chlorine, bromine or iodine, hal is halogen and L is a leaving group.

The compounds of the invention show fungicidal activity across a range of plant diseases. They are, however, particularly active against the class of pathogens knovn as the phycomycetes (equivalent to the oomycetes). These include species of Phytophthora, Plasmopara, Peronospora and Pseudoperonospora. Examples of pathogens vhich the invention compounds are particularly useful for controlling are: Plasmopara viticola on vines; other downy mildews such as Bremia lactucae on lettuce; Peronospora spp. on soybeans, tobacco, onions and other hosts; Pseudoperonospora humuli on hops and Pseudoperonospora cubensis on cucurbits; Phytophthora infestans on potatoes and tomatoes and other Phytophthora spp. on vegetables, strawberries, avocado, pepper, ornamentals, tobacco, cocoa and other hosts; and Pythium sp on rice, horticultural plants, vegetables and turf.

The invention therefore provides a method of combating fungi vhich comprises applying to a plant, to a seed of a plant or to the locus of the plant or seed a fungicidally effective amount of a compound as hereinbefore defined, or a composition containing the same.

The compounds may be used directly for agricultural purposes but are more conveniently formulated into compositions using a carrier or diluent. The invention thus provides fungicidal compositions comprising a compound as hereinbefore defined and an acceptable carrier or diluent therefor.

The compounds can be applied in a number of ways. For example, they can be applied, formulated or unformulated, directly to the foliage of a plant, to seeds or to other medium in which plants are growing or are to be planted, or they can be sprayed on, dusted on or applied as a cream or

AP Ο Ο Ο 2 7 6

- 8 paste formulation, or they can be applied as a vapour or as slow release granules.

Application can be to any part of the plant including the foliage, stems, branches or roots, or to soil surrounding the roots, or to the seed before it is planted, or to the soil generally, to paddy water or to hydroponic culture systems. The invention compounds may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods.

The term plant as used herein includes seedlings, bushes and trees. Furthermore, the fungicidal method of the invention includes preventative, protectant, prophylactic and eradicant treatments.

The compounds are preferably used for agricultural and horticultural purposes in the form of a composition. The type of composition used in any instance will depend upon the particular purpose envisaged.

The compositions may be in the form of dustable powders or granules comprising the active ingredient (invention compound) and a solid diluent or carrier, for example, fillers such as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, fuller's earth, gypsum, diatomaceous earth and china clay. Such granules can be preformed granules suitable for application to the soil without further treatment. These granules can be made either by impregnating pellets of filler with the active ingredient or by pelleting a mixture of the active ingredient and powdered filler. Compositions for dressing seed may include an agent (for example, a mineral oil) for assisting the adhesion of the composition to the seed; alternatively the active ingredient can be formulated for seed dressing purposes using an organic solvent (for example, N-methylpyrrolidone, propylene glycol or N,N-dimethylformamide). The compositions may also be in the form of wettable powders or water dispersible granules comprising wetting or dispersing agents to facilitate the dispersion in liquids. The powders and granules may also contain fillers and suspending agents.

Emulsifiable concentrates or emulsions may be prepared by dissolving the active ingredient in an organic solvent optionally containing a vetting or emulsifying agent and then adding the mixture to vater vhich may also contain a wetting or emulsifying agent. Suitable organic solvents are aromatic solvents such as alkylbenzenes and alkylnaphthalenes, ketones such as cyclohexanone and methylcyclohexanone, chlorinated hydrocarbons such as

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- 9 chlorobenzene and trichlorethane, and alcohols such as benzyl alcohol, furfuryl alcohol, butanol and glycol ethers.

Suspension concentrates of largely insoluble solids may be prepared by ball or bead milling vith a dispersing agent vith a suspending agent included to stop the solid settling.

Compositions to be used as sprays may be in the form of aerosols vherein the formulation is held in a container under pressure of a propellant, e.g. fluorotrichloromethane or dichlorodifluoromethane.

The invention compounds can be mixed in the dry state vith a pyrotechnic mixture to form a composition suitable for generating in enclosed spaces a smoke containing the compounds.

Alternatively, the compounds may be used in micro-encapsulated form. They may also be formulated in biodegradable polymeric formulations to obtain a slov, controlled release of the active substance.

By including suitable additives, for example additives for improving the distribution, adhesive pover and resistance to rain on treated surfaces, the different compositions can be better adapted for various utilities. Other additives may be included to improve the biological efficacy of the various formulations. Such additives can be surface active materials to improve the vetting and retention on surfaces treated vith the formulation and also the uptake and mobility of the active material, or additionally can include oil based spray additives. For example, certain mineral oil and natural plant oil (such as soya bean and rape seed oil) additives have been found to enhance several-fold foliar protectant activity against, for example, Plasmopara viticola.

The invention compounds can be used as mixtures vith fertilisers (e.g. nitrogen-, potassium- or phosphorus-containing fertilisers). Compositions comprising only granules of fertiliser incorporating, for example coated vith, the compound are preferred. Such granules suitably contain up to 25Z by veight of the compound. The invention therefore also provides a fertiliser composition comprising a fertiliser and the compound of general formula (I) or a salt or metal complex thereof.

Uettable povders, emulsifiable concentrates and suspension concentrates vill normally contain surfactants, e.g. a vetting agent, dispersing agent, emulsifying agent or suspending agent. These agents can be cationic, anionic or non-ionic agents.

Suitable cationic agents are quaternary ammonium compounds, for example, cetyltrimethylammonium bromide. Suitable anionic agents are

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- 10 soaps, salts of aliphatic monoesters of sulphuric acid (for example, sodium lauryl sulphate), and salts of sulphonated aromatic compounds (for example, sodium dodecylbenzenesulphonate, sodium, calcium or ammonium lignosulphonate, butylnaphthalene sulphonate, and a mixture of sodium diisopropyl- and triisopropylnaphthalene sulphonates).

Suitable non-ionic agents are the condensation products of ethylene oxide vith fatty alcohols such as oleyl or cetyl alcohol, or vith alkyl phenols such as octyl- or nonylphenol and octylcresol. Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, the condensation products of the said partial esters vith ethylene oxide, and the lecithins. Suitable suspending agents are hydrophilic colloids (for example, polyvinylpyrrolidone and sodium carboxymethylcellulose), and svelling clays such as bentonite or at tapulgi te.

Compositions for use as aqueous dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being diluted vith vater before use. These concentrates should preferably be able to vithstand storage for prolonged periods and after such storage be capable of dilution vith vater in order to form aqueous preparations vhich remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. The concentrates may conveniently contain up to 95Z, suitably 10-85Z, for example 25-6OZ, by veight of the active ingredient. After dilution to form aqueous preparations, such preparations may contain varying amounts of the active ingredient depending upon the intended purpose, but an aqueous preparation containing 0.0005Z or 0.01Z to 10Z by veight of active ingredient may be used.

The compositions of this invention may contain other compounds having biological activity, e.g. compounds having similar or complementary fungicidal activity or vhich possess plant grovth regulating, herbicidal or insecticidal activity.

A fungicidal compound vhich may be present in the composition of the invention may be one vhich is capable of combating ear diseases of cereals (e.g. vheat) such as Septoria, Gibberella and Helminthosporium spp., seed and soil-borne diseases and dovny and povdery mildevs on grapes and povdery mildev and scab on apple, etc. By including another fungicide, the composition can have a broader spectrum of activity than the compound of general formula (I) alone. Further the other fungicide can have a

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- 11 synergistic effect on the fungicidal activity of the compound of general formula (I). Examples of fungicidal compounds vhich may be included in the composition of the invention are (RS)-l-aminopropylphosphonic acid, (RS)-4-(4-chlorophenyl)-2-pheny1-2-(1H-1,2,4-triazol-l-ylmethyl)butyroni trile, (Z)-N-but-2-enyloxymethyl-2-chloro-2',6'-diethylacetanilide, l-(2-cyano-2-methoxyiminoacetyl)-3-ethyl urea, 3-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-l-yl)quinazolin-4(3H)-one, 4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylbenzimidazole-l-sulphonamide, 5-ethyl-5,8-dihydro-8-oxo(l,3)-dioxol(4,5-g)quinoline-7-carboxylic acid, a-[N-(3-chloro-2,6-xylyl)-2-methoxyacetamidoj-y-butyrolactone, aldimorph, anilazine, benalaxyl, benomyl, biloxazol, binapacryl, bitertanol, blasticidin S, bromuconazole, bupirimate, buthiobate, captafol, captan, carbendazim, carboxin, chlorbenzthiazone, chloroneb, chlorothalonil, chlorozolinate, copper containing compounds such as copper oxychloride, copper sulphate and Bordeaux mixture, cycloheximide, cymoxanil, cyproconazole, cyprofuram, di-2-pyridyl disulphide 1,1'-dioxide, dichlofluanid, dichlone, diclobutrazol, diclomezine, dicloran, difenoconazole, dimethamorph, dimethirimol, diniconazole, dinocap, ditalimfos, dithianon, dodemorph, dodine, edifenphos, etaconazole, ethirimol, ethyl (Z)-N-benzyl-N-([methyl(methylthioethylideneamino-oxycarbonyl)amino]thio)-6-alaninate, etridiazole, fenapanil, fenarimol, fenfuram, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, flutolanil, flutriafol, flusilazole, folpet, fosetyl-aluminium, fuberidazole, furalaxyl, furconazole-cis, guazatine, hexaconazole, hydroxyisoxazole, imazalil, imibenconazole, iprobenfos, iprodione, isoprothiolane, kasugamycin, mancozeb, maneb, mepanipyrim, mepronil, metalaxyl, methfuroxam, metsulfovax, myclobutanil, neoasozin, nickel dimethyldithiocarbamate, nitrothal-isopropyl, nuarimol, ofurace, organomercury compounds, oxadixyl, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazin oxide, phthalide, polyoxin D, polyram, probenazole, prochloraz, procymidone, propamocarb, propiconazole, propineb, prothiocarb, pyrazophos, pyrifenox, pyroquilon, pyroxyfur, pyrrolnitrin, quinomethionate, quintozene, SSF-1O9, streptomycin, sulphur, tebuconazole, techlofthalam, tecnazene, tetraconazole, thiabendazole, thicyofen, thiophanate-methyl, thiram, tolclofos-methyl, triacetate salt of 1,1' - iminodi (octamethylene)diguanidine, triaditnefon, triadimenol, triazbutyl, tricyclazole, tridemorph, triforine, validamycin A, vinclozolin, zarilamid and zineb. The compounds of general formula (I) can

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- 12 be mixed vith soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases.

Suitable insecticides vhich may be incorporated in the composition of the invention include buprofezin, carbaryl, carbofuran, carbosulfan, chlorpyrifos, cycloprothrin, demeton-s-methyl, diazinon, dimethoate, ethofenprox, fenitrothion, fenobucarb, fenthion, formothion, isoprocarb, isoxathion, monocrotophos, phenthoate, pirimicarb, propaphos and XMC.

Plant grovth regulating compounds are compounds vhich control veeds or seedhead, formation, or selectively control the grovth of less desirable plants (e.g. grasses).

Examples of suitable plant grovth regulating compounds for use vith the invention compounds are 3,6-dichloropicolinic acid,

1-(4-chlorophenyl)-4,6-di-me thy1-2-oxo-1,2-dihydropyridine-3-carboxylic acid, methyl-3,6-dichloroanisate, abscisic acid, asulam, benzoylprop-ethyl, carbetamide, daminozide, difenzoquat, dikegulac, ethephon, fenpentezol, fluoridamid, glyphosate, glyphosine, hydroxybenzonitriles (e.g. bromoxynil), inabenfide, isopyrimol, long chain fatty alcohols and acids, maleic hydrazide, mefluidide, morphactins (e.g. chlorfluoroecol), paclobutrazol, phenoxyacetic acids (e.g. 2,4-D or MCPA), substituted benzoic acid (e.g. triiodobenzoic acid), substituted quaternary ammonium and phosphonium compounds (e.g. chloromequat, chlorphonium or mepiquatchloride), tecnazene, the auxins (e.g. indoleacetic acid, indolebutyric acid, naphthylacetic acid or naphthoxyacetic acid), the cytokinins (e.g. benzimidazole, benzyladenine, benzylaminopurine, diphenylurea or kinetin), the gibberellins (e.g. GA^, GA^ or GA?) and triapenthenol.

The folloving Examples illustrate the invention.

Throughout the Examples the term 'ether' refers to diethyl ether, magnesium sulphate vas used to dry solutions and solutions vere concentrated under reduced pressure. Vhere shovn, infrared and NMR data are selective; no attempt is made to list every absorption in all cases.

The folloving abbreviations are used throughout:

s = singlet d = doublet dd = doublet of doublets t = triplet m = multiplet b = broad mp = melting point DMF = N,N-dimethylformamide

NMR = nuclear magnetic resonance

AP Ο Ο Ο 2 7 6

- 13 EXAMPLE 1

This example illustrates the preparation of 4-trimethylacetamido-2iodo-N,N-dimethylbenzamide (Compound No. 1 of Table I).

Step 1

Preparation of 4-nitro-2-trifluoroacetamidobenzoic acid.

To a stirred suspension of 4-nitroanthranilic acid (lOg) in dry ether (600ml) was added sodium carbonate (80g). The suspension was cooled to 2°C and trifluoroacetic anhydride (85ml) was added dropwise. The resulting yellow-green mixture was warmed to room temperature and stirred for 5 hours before being poured into chloroform. Excess anhydride was destroyed with ice and the organic layer was washed with water, dried, filtered, and concentrated under reduced pressure to give an orange solid.

Chromatography on silica, eluting with ethyl acetate/hexane/acetic acid (50:60:5) gave 4-nitro-2- trifluoroacetamidobenzoic acid (4g) as a yellow solid; *H NMR (CDClp 270 MHz) δ 8.06(lH,d), 8.38(lH,d), 9.47(lH,bs), 13.22(lH,bs) ppm; mp 130°C (decomposition).

Step 2

Preparation of 4-nitro-2-tri fluoroacetamido-N,N-dimethylbenzamide.

To a stirred suspension of 4-nitro-2-trifluoroacetamidobenzoic acid (3.5g) and DMF (3 drops) in dichloromethane (30ml) was slowly added oxalyl chloride (1.1ml). Further dichloromethane (70ml) was added to solubilize the mixture which was stirred for 1.5 hours before being slowly added to dimethylamine (40X w/w aq.; 14ml) and 4-dimethylaminopyridine (catalytic amount) at 5°C. The resulting bright-yellow mixture was stirred for 1.5 hours at 5®C, then washed with dilute aqueous HCI, saturated aqueous sodium bicarbonate, and water. The organic layer was dried, filtered, and concentrated under reduced pressure to give a yellow oil (3g) which solidified on treatment with ethyl acetate/hexane (1:1). Trituration with a small amount of ethyl acetate/hexane (1:1) gave 4-nitro-2-trifluoroacetamido-N,N-dimethylbenzamide as a pale yellow solid (1.85g); ^H NMR (CDC1₃, 270 MHz) S: 3.15(6H,bs), 7.55(lH,d), 8.08(lH,dd), 9.18(lH,s), 10.55(lH,s) ppm; mp 139.5-140.5°C.

^.Ρ, ³

Preparation of 4-amino-2-trifluoroacetamido-N,N-dimethylbenzamide.

Palladium on charcoal (10X on charcoal; catalytic amount) was flushed well with argon. 4-nitro-2-trifluoroacetamido-N,N-dimethylbenzamide (1.3g) in methanol (4.5ml) was added and the reaction vessel flushed three times with hydrogen and kept under hydrogen for 3 hours. The mixture was twice

AP Ο Ο Ο 2 7 6

- 14 filtered through hyflo and through filter paper to remove the catalyst. Concentration under reduced pressure gave 4-amino-2-trifluoroacetamido-N,N dimethylbenzamide as a pale yellow solid (1.09g); NMR (CDCl^, 270 MHz) δ: 3.1(6H,s), 4.7(2H,s), 6.45(lH,dd), 7.17(lH,d), 7.68(lH,s), 11.4(lH,s) ppm; mp 17O-171°C.

Step 4

Preparation of 4-1rimethylacetamido-2-tri fluoroacetamido-N,N-dimethyl benzamide.

Trimethylacetyl chloride (384yl) was added dropwise to a stirred solution of 4-amino-2-trifluoroacetamido-N,N-dimethylbenzamide (800mg), triethylamine (610μ1), and 4-dimethylaminopyridine (catalytic amount) in dichloromethane (40ml). After 18 hours, the reaction mixture was washed with dilute aqueous HCl, saturated aqueous sodium bicarbonate, and water, dried, filtered and concentrated under reduced pressure to give an orange oil which crystallised on trituration with hexane. Chromatography on silica, eluting with hexane/ethyl acetate (1:1) gave 4-triraethylacetamido-2-trifluoroacetamido-N,N-dimethylbenzamide as white crystals; ^H NMR (CDClp 270MHz) δ: 1.3(9H,s), 3.1(6H,s), 7.45(lH,d), 7.68(lH,s), 7.96(lH,dd), 8.1(lH,s) ppm; mp 190-191’C.

Step 5

Preparation of 4-trimethylacetamido-2-amino-N,N-dimethylbenzamide.

To a stirred solution of potassium carbonate in aqueous methanol (40ml; 7Z; 2:5 v/v) was added 4-trimethylacetamido-2-trifluoroacetamido-Ν,Ν-dimethylbenzamide (360mg). After 32 hours, the reaction mixture was poured into water and the product extracted with ether (2x). The combined organic extracts were dried, filtered, and concentrated under reduced pressure to give 4-trimethylacetamido-2-amino-N,N-dimethylbenzamide as a yellow solid (164mg); ^XH NMR (CDC1₃, 270MHz) δ: 1.3(9H,s), 3.05(6H,s), 4.65(lH,bs), 6.85(lH,dd), 7.03(lH,d), 7.22(lH,s), 8.10(lH,s) ppm; mp 175-175.5’C.

Step 6

Preparation of 4-trimethylacetamido-2-iodo-N,N-dimethylbenzamide.

A solution of sodium nitrite (220mg) in water (1ml) was added to stirred solution of 4-trimethylacetamido-2-amino-N,N-dimethylbenzamide (740mg) in concentrated aqueous HCl (5ml) keeping the temperature below 0°C. After 15 minutes kept at -2°C, the reaction mixture vas added to aqueous potassium iodide (560mg in 2ml) and stirred overnight. The mixture vas dissolved in ethyl acetate and washed with aqueous sodium hydroxide

AP Ο Ο Ο 2 7 6

- 15 (1ΟΧ), water, aqueous sodium sulfate (5X), and vater. The organic extract was dried, filtered, and concentrated under reduced pressure to give a yellov solid (610mg). Chromatography on silica, eluting vith ethyl acetate gave 4-trimethylacetamido-2-iodo-N,N-dimethylbenzamide as a pale yellov solid (200mg); ^XH NMR (CDCl₃,27O MHz) 8: 1.3(9H,s), 2.85(3H,s), 3.12(3H,s), 7.02(lH,d), 7.47(lH,s), 7.9(lH,s), 8.0(lH,s) ppm; mp 228.5-230.5^eC.

The folloving are examples of compositions suitable for agricultural and horticultural purposes vhich can be formulated from the compounds of the invention. Such compositions form another aspect of the invention. Percentages are by veight.

EXAMPLE 2

This Example illustrates the preparation of 4-(2-fluoro-2-methylpropanamido)-2-iodo-N,N-dimethylbenzamide (Compound No. 5 of Table I).

Step 1

Preparation of 2-iodo-4-nitrobenzoic acid.

To a stirred solution of 4-nitroanthranilic acid (1.82g) in concentrated aqueous HCl (30ml) cooled to -5°C vas added sodium nitrite (760mg) in vater (3ml) keeping the temperature belov O’C. The mixture vas cooled to -5°C and, after 15 minutes, it vas added to a solution of potassium iodide (2g) in vater (10ml) and stirred for 20 hours. The mixture vas diluted vith ethyl acetate, and the organic layer vashed vith 10X aqueous sodium thiosulphate, dried (MgSO^) and concentrated under reduced pressure to give a yellov solid (1.83g) vhich vas used vithout further purification in Step 2; ^ΣΗ NMR (270MHz; CDCl-j) 6 8.12(lH,d), 8.3(lH,dd), 8.88(lH,d) ppm.

Step., 2

Preparation of 2-iodo-4-nitro-N,N-dimethylbenzamide.

Oxalyl chloride (6.7ml) vas added dropvise to a stirred suspension of 2-iodo-4-nitrobenzoic acid (23g) in dichlormethane (200ml) under a nitrogen atmosphere. After 2.5 hours, all the solid had dissolved. The solution vas added to dimethylamine (40X aq; 41ml) and the resulting mixture vas stirred for 4.5 hours. The dichioromethane solution vas vashed vith dilute aqueous HCl, saturated aqueous sodium bicarbonate and vater, dried (MgSO^) and concentrated under reduced pressure to give the product as a dark yellov solid (22.09g); ^ΣΗ NMR (270MHz; CDCl-j) δ 2.85(3H,s), 3.18(3H,s), 7.39(lH,d), 8.28(lH,dd), 8.69(lH,dd) ppm.

AP Ο Ο Ο 2 7 6

- 16 Step 3

Preparation of 4-amino-2-iodo~N,N-dimethylbenzamide.

2-iodo-4-nitro-N,N-dimethylbenzamide (1.28g) vas added portionwise to a solution of tin-II-chloride (2.3g) in concentrated aqueous HCl at O’C.

The mixture vas warmed to room temperature after 20 minutes. After 1 hour, the mixture vas poured into vater, basified vith aqueous sodium hydroxide and extracted twice vith dichloromethane. The combined organic extracts were dried (MgSO^) and concentrated under reduced pressure to give the product as a yellov solid (950mg); ^H NMR (270MHz; CDCip δ 2.88(3H,s), 3.1O(3H,s), 3.79(2H,s), 6.65(lH,dd), 6.97(lH,d), 7.12(lH,dd) ppm.

Step 4

Preparation of 4-(2-fluoro-2-methylpropanamido)-2-iodo-N,N-dimethylbenzamide.

A solution of 2-fluoro-2-methylpropanoyl chloride vas prepared by treatment of 2-fluoro-2-methylpropanoic acid (426mg) and DMF (2 drops) in dichloromethane (5ml) vith oxalyl chloride (350yl) and stirring for 1.5 hours. The solution vas added dropvise to a stirred solution of

4-amino-2-iodo-N,N-dimethylbenzamide (950mg), triethyiamine (0.7ml) and Ν,Ν-dimethylaminopyridine (catalytic amount) in dichloromethane (45ml) and the mixture stirred for 2 hours. The solution vas washed vith dilute aqueous HCl, saturated aqueous sodium bicarbonate and vater, dried (MgSO^) and concentrated under reduced pressure to give a yellov foam (985mg). Chromatography on silica, eluting vith ethyl acetate, gave the product as a cream solid (850mg); mp 165.5-168’C.

EXAMPLE 3

This Example illustrates the preparation of 4-(2-fluoro-2-methylpropanamido)-2-ethynyl-N,N-dimethylbenzamide (Compound No. 33 of Table I). Step 1

Preparation of 4-nitro-2-(2-trimethylsilylethynyl)-N,Ndimethylbenzamide.

A mixture of 2-iodo-4-nitro-N,N-dimethylbenzamide (from Example 2,

Step 2) (1.92g), trimethylsilylethyne (1ml), bis(triphenylphosphine)palladium-II-chloride (192mg), copper-I-iodide (192mg) and triethyiamine (1.3ml) in acetonitrile (40ml) vas stirred under a nitrogen atmosphere for hours. The reaction mixture vas diluted vith ether, washed vith dilute aquesous HCl, vater and aqueous ammonia, dried (MgSO.) and concentrated ⁴ 1 under reduced pressure to give the product as a yellov solid; H NMR

APO 00 2 7 6

- 17 (270MHz; CDCip δ (inter alia) 2.9O(3H,s), 3.15(3H,s), 7.5O(lH,d), 8.20(lH,dd), 8.32(lH,d) ppm.

Step 2

Preparation of 4-nitro-2-ethynyl~N,N-dimethylbenzamide.

4-Ni tr0-2-(2-1rimethylsilylethynyl)-N,N-dimethylbenzamide (1.58g) vas dissolved in methanol (30ml) and potasium carbonate (200mg) vas added in one portion. After 1 hour, the solids were removed by filtration, and the filtrate concentrated under reduced pressure and redissolved in dichloromethane. The solution vas vashed vith vater, dried (HgSO^) and concentrated under reduced pressure to give a dark yellov solid vhich vas used in Step 3 vithout further purification; ^H NMR (270MHz; CDCl^) δ 2.9O(3H,s), 3.35(lH,s), 3.18(3H,s), 7.50(lH,d), 8.25(lH,dd), 8.39(lH,d) ppm.

Step 3

Preparation of 4-amino-2-ethynyl-N,N-dimethylbenzamide.

4-Nitro-2-ethynyl-N,N-dimethylbenzamide (960mg) vas added portionvise to a solution of tin-II-chloride (2.5g) in concentrated aqueous HCl (30·1) at O°C. After 1 hour, the mixture vas poured into vater and basified vith aqueous sodium hydroxide. The aqueous layer vas extracted vith dichloromethane, dried (MgSO^) and concentrated under reduced pressure to give a yellov oil (760mg) vhich vas used vithout further purification in Step 4; ^TH NMR (270MHz; CDCl-j) δ 2.9O(3H,s), 3.10(3H,s), 3.1O(lH,s), 3.80(2H,bs), 6.68(lH,dd), 6.79(lH,d), 7.10(lH,d) ppm.

Step 4

Preparation of 4-(2-fluoro-2-methylpropanamido)-2-ethynyl-N,N-dimethylbenzamide.

A solution of 2-fluoro-2-methylpropanoyl chloride vas prepared by treatment of 2-fluoro-2-methylpropanoic acid (263mg) and DMF (3 drops) in dichloromethane (10ml) vith oxalyl chloride (215ul) and stirring for 1.5 hours. The solution vas added dropvise to a stirred solution of 4-amino2-ethynyl-N,N-dimethylbenzamide (360mg), triethylamine (0.6ml) and Ν,Ν-dimethylaminopyridine (catalytic amount) in dichloromethane (25ml) and the mixture stirred for 1.5 hours. The solution vas vashed vith dilute aqueous HCl, saturated aqueous sodium bicarbonate and vater, dried (MgSO^) and concentrated under reduced pressure to give a brovn oil (590mg) vhich crystallised on standing. Chromatography on silica, eluting vith ethyl acetate, gave the pure product as a yellov oil vhich cryatallised on standing (317mg); mp 110°C (decomp.)

AP Ο ο ο 2 7 6

- 18 EXAMPLE 4

This Example illustrates the preparation of 4-(2-fluoro-2-methylpropanamido)-2-ethenyl-N,N-dimethylbeazamide (Compound No. 34 of Table I). Step 1

Preparation of 4-nitro-2-ethenyl-N,N-dimethylbenzamide.

A stirred mixture of 2-iodo-4-nitro-N,N-dimethylbenzamide (from Example 2, Step 2) (lg), bis(triphenylphosphine)palladium-II-chloride (80mg) and vinyltributyltin (915pl) in dry DMF (20ml) vas heated at 70°C under a nitrogen atmosphere for 12 hours. The cooled mixture vas added to aqueous potassium fluoride (10Z) and ether, and the resulting mixture stirred for 1 hour before filtration through hyflo. The ether layer vas separated and the aqueous layer further extracted vith ether. The combined ether extracts vere washed vith brine, dried (MgSOp and concentrated under reduced pressure to give an orange oil vhich was triturated vith hexane.

The residue vas used without further purification in Step 2; ^8 NMR (270MHz; CDCip δ 2.50(3H,s), 3.16(38,s), 5.52(lH,d), 5.95(18,d), 6.73(lH,dd), 7.40(lH,d), 8.15(18,dd), 8.44(18,d) ppm.

Step 2

Preparation of 4-amino-2-ethenyl-N,N-dimethylbenzamide.

4-Nitro-2-ethenyl-N,N-dimethylbenzamide (690mg) vas added portionwise to a soltuion of tin-II-chloride (1.8g) in concentrated aqueous HCl (30ml) at 0*C. After 1 hour, the mixture vas poured into vater and basified with aqueous sodium hydroxide. The insoluble materials vere removed by filtration. The aqueous layer was extracted with dichloromethane, dried (MgSO.) and concentrated under reduced pressure to give a yellow oil * 1 (457mg) vhich was used without further purification in Step 3; H NMR (270MHz; CDCip δ 2.80(3H,s), 3.11(3H,s), 3.78(2H,s), 5.26(lH,d), 5.67(lH,d), 6.61(18,dd), 6.65(18,dd), 6.85(18,d), 7.03(18,d) ppm.

Step 3

Preparation of 4-(2-fluoro-2-methylpropanamido)-2-ethenyl-N,Ndimethylbenzamide.

A solution of 2-fluoro-2-methylpropanoyl chloride vas prepared by treatment of 2-fluoro-2-methylpropanoic acid (300mg) and DMF (2 drops) in dichloromethane (5ml) vith oxalyl chloride (250ul) and stirring for 1 hour. The solution was added dropwise to a stirred solution of 4-amino-2-ethenylΝ,Ν-dimethylbenzamide (450mg), triethylamine (0.5ml) and N,N-dimethylaminopyridine (catalytic amount) in dichloromethane (20ml) and the mixture stirred for 1 hour. The solution vas washed vith dilute aqueous BCl,

AP Ο 00 2 7 6

- 19 saturated aqueous sodium bicarbonate and water, dried (MgSO^) and concentrated under reduced pressure to give a yellow oil vhich crystallised on standing. Recrystallisation from ethyl acetate/hexane gave the product as yellow crystals (327mg); mp 164-165°C.

EXAMPLE 5

An emulsifiable concentrate is made up by mixing and stirring the ingredients until all are dissolved.

Compound No. 1 of Table I 10%

Benzyl alcohol 30%

Calcium dodecylbenzenesulphonate 5%

Nonylphenolethoxylate (13 mole ethylene oxide) 10%

Alkyl benzenes 45%

EXAMPLE 6

The active ingredient is dissolved in methylene dichloride and the resultant liquid sprayed on to the granules of attapulgite clay. The solvent is then allowed to evaporate to produce a granular composition. Compound No. 1 of Table I 5%

Attapulgite granules 95%

EXAMPLE 7

A composition suitable for use as a seed dressing is prepared by grinding and mixing the three ingredients.

Compound No. 1 of Table I 50%

Mineral oil 2%

China clay 48%

EXAMPLE 8

A dustable powder is prepared by grinding and mixing the active ingredient vith talc.

Compound No. 1 of Table I 5%

Talc 95%

EXAMPLE 9

A suspension concentrate is prepared by ball milling the ingredients to form an aqueous suspension of the ground mixture vith water.

Compound No. 1 of Table I 40%

Sodium lignosulphonate 10%

Bentonite clay 1%

Water 49%

This formulation can be used as a spray by diluting into water or applied directly to seed.

AP Ο Ο Ο 2 7 6

- 20 EXAMPLE 10

A vettable povder formulation is made by mixing together and grinding

the ingredients until all are	thoroughly mixed.
Compound No. 1 of Table I		252
Sodium lauryl sulphate		22
Sodium lignosulphonate		52
Silica		252
China clay		432
	EXAMPLE 11

The compounds were tested against a variety of foliar fungal diseases of plants. The technique employed was as follows.

The plants were grown in John Innes Potting Compost (No. 1 or 2) in 4cm diameter minipots. The test compounds were formulated either by bead milling vith aqueous Dispersol T or as a solution in acetone or acetone/ethanol which was diluted to the required concentration immediately before use. For the foliage diseases, the formulations (100 ppm active ingredient) were sprayed onto the foliage and applied to the roots of the plants in the soil. The sprays were applied to maximum retention and the root drenches to a final concentration equivalent to approximately 40 ppm a.i. in dry soil. Tveen 20, to give a final concentration of 0.052, vas added vhen the sprays vere applied to cereals.

For most of the tests the compound vas applied to the soil (roots) and to the foliage (by spraying) one or tvo days before the plant vas inoculated vith the disease. An exception vas the test on Erysiphe graminis in which the plants vere inoculated 24 hours before treatment. Foliar pathogens vere applied by spray as spore suspensions onto the leaves of test plants. After inoculation, the plants vere put into an appropriate environment to allov infection to proceed and then incubated until the disease was ready for assessment. The period between inoculation and assessment varied from four to fourteen days according to the disease and environment.

The disease control vas recorded by the following grading:

= no disease = trace-52 of disease on untreated plants = 6-252 of disease on untreated plants = 26-592 of disease on untreated plants = 60-1002 of disease on untreated plants

AP Ο Ο Ο 2 7 6

- 21 The results are shown in Table II.

TABLE II

Compound No.	Pr	Egt	Sn	Po	Vi	Pv	Pil ·
1	0	0	0	0	0	4	4
5	0a	0a	0a	0a	oa	4a	4a
13	0	3	3	3	4	3	3
19	0a	0a	0a	0a	3a	oa	0a
23	oa	0a	0a	0a	0a	4a	0a
29	-	1	1		0	0	0
30						4b	ob
31						4b	3b
32	-	-	-	-	-	4b	3b
33	-	0	-	0	0	4	4
34	-	0	-	0	4	4	4
35	-	0	-	0	0	4	4

a = root drench application only @ 25 ppm. b = root drench application only @ 100 ppm.

Key to Diseases

Pr Puccinia recondita

Egt Erysiphe graminis tritici

Sn Septoria nodorum

Po Pyricularia oryzae

Vi Venturia inaequalis

Pv Plasmopara viticola

Pil Phytophthora infestans lycopersici

AP Ο Ο Ο 2 7 6

- 22 CHEMICAL FORMULAE (in description)

Scheme 1

(I)

(III)

(VI) I

(VII)

(II)

(IX)

AP Ο Ο Ο 2 7 6

- 23 Scheme 2

(ID (XIX)

AP Ο ο Ο 2 7 6

(XII)

(XIII)

Β¹

C _χΒ

Ν \ 2

1C (XIV)

R⁸

I

F-C — *9

R (XV)

AP Ο Ο Ο 2 7 6

(XVI) fch₂—

(XVII)

(XVIII)

Ν \r² (XIX)

R Ο • II

FCH-C— C—Cl ²lg

R^y (XX)

AP Ο Ο Ο 2 7 6

(XXI)

(XXII)

R ¹ R OCH--C ² I (XXIII)

(XXIV)

AP000276

Claims (8)

1. CLAIMS in which A and B are independently H, iodo, nitro, cyano, alkoxycarbonyl, alkoxy(C^ ^)alkyl, alkylthio(C^ ^)alkyl, formyl, C , alkylthio, halo(C )alkylthio, halo(C )alkoxy,

   X “ 5 θ X - *4 g X — *4 ^alkylcarbonyl, -CR »NOR (where R and R are independently H or C^ alkyl), C? alkenyl or alkynyl, provided that A and B are not both H; D and E are independently H or fluoro; R^ is H, C_] alkyl
2. 2 1 2¹* or C^ alkoxy; R is C ₄ alkyl or alkoxy, or R and R together with the nitrogen atom to which they are attached join to form a morpholine, piperidine, pyrrolidine or azetidine ring which is 3 4 optionally substituted with C alkyl; R is H; R is trichloromethyl, C alkyl (optionally substituted with halogen, C,

   Z-o 1-8 alkoxy or R’S(O) in which R’ is C, . alkyl, C„ . alkenyl or C„ , alkynyl and n is 0, 1 or 2), cyclopropyl (optionally substituted with halogen or C^ alkyl), C₂__g alkenyl, C₂__g alkynyl or C₂__g alkoxy (each of which is optionally substituted with halogen), mono- or di(C Jalkylamino or the group, R0N=C(CN) in which R is C alkyl, 3 ’ 4 or R and R together with the group C(0)N to which they are attached join to form an azetidin-2-one ring which is optionally substituted with halogen or C^ alkyl; and X and Y are independently oxygen or sulphur.

   2. A compound according to claim 1 in which R is R(CH₃)₂C, where R is halo, C^ alkyl or C^ alkoxy.
3. 3. A compound according to claim 1 in which R is FiCH^^C.

   AP Ο Ο Ο 2 7 6

   - 28 4 8 9 8

   A compound according to claim 1 in vhich R is F(R )(R )C, vhere R 9 and R are independently H, Cj * alkyl or halo(Cj palkyl.

   A compound according to claim 1 in vhich A is iodo, cyano, nitro, Cj alkoxycarbonyl, Cj_₄ alkylcarbonyl, Cj alkoxy(Cj ^)alkyl, Cj alkylthio, formyl, C. , alkylthioiC. ,)alkyl or -CH=NOR⁶ (vhere R⁴ is Cjalkyl); R and R are alkyl; R , B, D and E are H; R^q is C₂ g alkyl optionally substituted vith halogen or Cj alkoxy; and X and Y are both oxygen.

   A process for preparing a compound according to claim 1 in vhich A is iodo, R^J is H and X and Y are both oxygen, vhich comprises treating a compound of formula (VIII):

   (VIII) vith nitrous acid and an iodide source; vherein B, D have the meanings given in claim 1.

   E, R¹, R² and R⁴

   A process for preparing a compound according to claim 1 in vhich A is 3 cyano or Cj alkylthio, R is H and X and Y are both oxygen, vhich comprises reacting a compound of formula (IX):

   CON (ix) vith a transition metal salt of a cyanide or C. , alkanethiolate in a 1 2 4⁴ suitable solvent; vherein B, D, E, R , R and R have the meanings given in claim 1.

   AP Ο Ο Ο 2 7 6

   - 29 8. A process for preparing a compound Y are both oxygen, vhich comprises formula (XIX):

   according to claim 1 in vhich X and reacting a compound of general (XIX) with an acid chloride R COCI in a suitable solvent in the presence of 12 4 a base; wherein A, B, D, E, R , R and R have the meanings given in claim 1.

   9. A process for preparing a compound according to claim 1, 3

   a) vhen X and Y are both oxygen and R is H,

   i) by reacting a compound of general formula (X):

   (X) ^N\_r2 vith an acid chloride R COCI in a suitable organic solvent in the presence of a base;

   ii) by reacting a compound of general formula (XI):

   (XI)

   1 2 vith an amine R R NH in a suitable organic solvent in the 1 2 presence of a base or excess R R NH; or

   AP Ο Ο Ο 2 7 6

   - 30 iii) by reacting a compound of general formula (XII):

   Z R¹ C\ _/R

   N \ 2 R (xii)

   A vith a compound of general formula R -CO-NHj and a base;

   3 A

   b) vhen X and Y are both oxygen and R^J and R^ together vith the group C(0)N form a ring of the formula (XIII):

   (ΧΙΠ)

   R⁵ R^6/

   i) by treating a compound of general formula (XIV):

   Z -R^{1 X}R² (XIV) vith a base in a tvo-phase system consisting of an organic solvent and vater in the presence of a phase-transfer catalyst;

   3 4

   c) vhen X and Y are both oxygen, R is H and R is the group (XV):

   R

   I

   F— C (XV)

   AP Ο Ο θ ^{2 7} 6

   - 31 i) by treating a compound of general formula (XVI):

   8 Ί

   Br—C R

   Z \ / ^N\ 2 R (XVI) vith a fluoride transfer reagent in a suitable solvent;

   d) when X and Y

   I (XVII)

   i) by treating a compound of general formula (XVIII):

   hoch₂— (XVIII) vith a fluorinating agent in a suitable solvent;

   e) vhen X is oxygen i) by treating or sulphur, Y a compound of is sulphur and R is H, general formula (II):

   (II) vith a thionation reagent in a suitable solvent to form either a compound of general formula (I) in vhich X is 3 oxygen, Y is sulphur and R is hydrogen or a mixture of a compound of general formula (I) in vhich X is oxygen, Y is

   - 32 3 sulphur and R is hydrogen and a compound of general formula 3 (I) in vhich X and Y are both sulphur and R is hydrogen;

   f) vhen X is sulphur, Y is oxygen and R is H,

   i) by reacting an isothiocyanate of general formula (XXI):

   (XXI)
4. 4 4 vith an organometallic reagent R Li or R Mg-hal in a suitable solvent at a temperature betveen -78®C and +25°C; or

   g) vith an vhen X and Y

   1 2 amine R R NH in are both oxygen, the presence of is H and R^ (XXII) a base; or is the group (XXIII):

   R⁸

   11 * ROCH.-C1’ (XXIII)

   i) by reacting a compound of general formula (XXIV):

   D

   B (XXIV)

   AP Ο Ο Ο 2 7 6

   - 33 vith a halide R^-hal in the presence of a base in a suitable solvent;

   12 4 wherein A, B, D, E, R , R and R (except where otherwise stated) have the meanings given in claim 1, R^ and R^b are H, C. , alkyl or halogen,
5. 8
6. 9 IT ⁴

   R and R are H, alkyl or Cj haloalkyl, R is Cj alkyl, X' is chlorine, bromine or iodine, hal is halogen and L is a leaving group.
7. 10. A fungicidal composition comprising a fungicidally effective amount of a compound according to claim 1 and a fungicidally acceptable carrier or diluent therefor.
8. 11. A method of combating fungi which comprises applying to plants, to the seeds of plants or to the locus of the plants or seeds, a compound according to claim 1 or a composition according to claim 10.