GB2216120A

GB2216120A - Tertiary amine compounds

Info

Publication number: GB2216120A
Application number: GB8902227A
Authority: GB
Inventors: Christopher John Urch; Vivienne Margaret Anthony
Original assignee: Imperial Chemical Industries Ltd
Current assignee: Imperial Chemical Industries Ltd
Priority date: 1988-02-22
Filing date: 1989-02-01
Publication date: 1989-10-04
Also published as: GB8902227D0; GB8804064D0

Abstract

Fungicidal compounds having the general formula (I): <IMAGE> and stereoisomers thereof, wherein R<1> to R<8> each represents a hydrogen atom or an alkyl or haloalkyl group containing from 1 to 4 carbon atoms, R<9> and R<10> each represents an alkyl or haloalkyl group containing from 1 to 4 carbon atoms or R<9> and R<10> together with the adjacent nitrogen atom form a heterocyclic ring which may optionally contain an additional heteroatom, X represents a hydrogen atom, a halogen atom or an alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy or aryloxy group, or a <IMAGE> group wherein R<11> to R<13> can be an alkyl group containing from 1 to 4 carbon atoms or a phenyl group; and acid addition salts and N-oxides thereof.

Description

TERTIARY AMINE COMPOUNDS This invention relates to tertiary amine compounds containing a cyclopentane ring which are useful as fungicides, to processes for preparing them, and to methods of using them to combat fungi, especially fungal Sinfections in plants.

According to the invention there are provided compounds having a general formula (I)

and stereoisomers thereof, wherein R1 to R8 each represents a hydrogen atom or an alkyl or haloalkyl group containing from 1 to 4 carbon atoms, R9 and R10 each represents an alkyl or haloalkyl group containing from 1 to 4 carbon atoms or R9 and R10 together with the adjacent nitrogen atom form a heterocyclic ring which may optionally contain an additional heteroatom, X represents a hydrogen atom, a halogen atom or an alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy or aryloxy group, or a

group wherein R11 to R13 can be an alkyl group containing from 1 to 4 carbon atoms or a phenyl group; and acid addition salts and N-oxides thereof.

The compounds of the invention are generally obtained in the form of mixtures of geometric isomers. However, these and other mixtures of optical isomers can be separated into individual isomers by methods in the art and such isomers constitute a part of the present invention.

When R9 and R10, together with the adjacent Natom, represent a heterocyclic ring this may be, for example, a piperidine, morpholine, thiomorpholine, pyrrolidine or piperazine ring and any of these rings may bear substituents such as one or more C14 alkyl groups or a phenyl group.

Alkyl groups containing from 1 to 4 carbon atoms represented by R1 to R13 may be either straight or branched chain groups, for example, methyl, ethyl, npropyl, iso-propyl, n-butyl, sec-butyl, iso-butyl or tert-butyl. Alkyl and alkoxy groups represented by X may be either straight or branched chain groups containing from 1 to 6 carbon atoms, cycloalkyl groups represented by X may be C36 cycloalkyl groups, e.g. cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl groups; or cycloalkylalkyl groups, e.g.

C4-8 cycloalkylalkyl groups.

Halogen atoms represented by X may be fluorine, chlorine or bromine atoms.

Alkenyl and alkynyl groups represented by X may contain from 2 to 6 carbon atoms.

Examples of X when this is aryl, aralkyl, aryloxy or aralkoxy are phenyl, benzyl, phenoxy and benzyloxy. These rings may be substituted with halogen (e.g. fluorine, chlorine or bromine), C16 alkyl [e.g. methyl, ethyl, propyl (n- or iso-propyl) and butyl (n-, sec-, iso-, or tert-butyl)], C1-6 alkoxy (e.g. methoxy, ethoxy, propoxy and butoxy), halo-C16-alkoxy (e.g. trifluoromethoxy), halo-C16- alkyl (e.g. trifluoromethyl), nitro, phenyl and phenoxy.

Examples of X when this is a silyl group are trimethylsilyl, triethylsilyl, t-butyldimethylsilyl and phenyldimethylsilyl. The thiophene ring may thus be unsubstituted or substituted with ring substituents as defined above. The X substituent may be at the 3-, 4-, or 5-positions of the thiophene ring and the 4- and 5-positions are preferred. The 5-position is preferred over the 4-position.

Examples of the compounds of the invention are shown in Table I. These correspond to general formula (I), the various substituents being shown in the columns.

In Table I the significance of the abbreviations is as follows Me = methyl l-Pr = propyl n-Bu = normal butyl i-Bu = isobutyl s-Bu = secondary butyl t-Bu = tertiary butyl TMS = trimethylsilyl.

TABLE I

COMPOUND MELTING NO. X R1 R2 R3 R4 R5 R6 R7 R8 NR9R10 POINT ( C) COMMENTS 1 5-TMS H H H H H H H H # (HC@) HCL salt 213-215 cis A@/N 2 5-TMS H H H H H H H H # (HC@) 176-187 HC@ salt decomposes trans Ar/N 3 5-TMS H H H H H H H H # 4 5-TMS H H H H H H H H # 5 5-TMS Me H H H H H H H # 6 5-TMS H Me H H H H H H # TABLE I (CONT/D)

COMPOUND MELTING NO. X R1 R2 R3 R4 R5 R6 R7 R8 NR9R10 POINT ( C) COMMENTS 7 5-TMS H H H H Me H H H # 8 5-TMS H H H H H H Me H # 9 5-TMS H H H H H H H H # 10 5-t-Bu H H H H H H H H # 11 5-i-Bu H H H H H H H H # TABLE I (CONT/D)

COMPOUND MELTING NO. X R1 R2 R3 R4 R5 R6 R6 R8 NR9R10 POINT ( C) COMMENTS 12 5-S-Bu H H H H H H H H # 13 5-n-Bu H H H H H H H H # 14 5-i-Pr H H H H H H H H # 15 5-Cl H H H H H H H H # Compounds of general formula (I)

wherein R1 to R3, R5 to R10 and X are as defined above and R4 is hydrogen can be prepared by reductive amination of compounds of general formula (II) ::

wherein R1 to R3, R5 to R8 and X are as defined above with an amine of general formula (III) HNR9R10 (III) wherein R9 and R10 are as defined above with a reducing agent, for instance formic acid, sodium cyanoborohydride or tetrabutylammonium cyanoborohydr ide.

Compounds of general formula (II) may be prepared by treatment of enones of general formula (IV)

wherein R1, R2 and R5 to R8 are as above with an organocuprate reagent of general formula (V)

wherein X is as defined above or an organozinc reagent of general formula (VI)

wherein X is as defined above, optionally in the presence of a catalytic amount of nickel acetylacetonate.

Compounds of general formula (IV), (V) and (VI) can be prepared by methods set out in the literature.

As an alternative compounds of general formula (II) may be prepared by treatment of a compound of general formula (VII)

wherein R2, R5 to R8 and X are as defined above with an organocuprate reagent of general formula (VIII) (Rl)2CuLi (VIII) wherein R1 is as defined above. For cases where R1=R3=hydrogen compounds of general formula (11) can be prepared by hydrogenation of compounds of general formula (VII) over the usual hydrogenation catalysts such as palladium on charcoal.

Compounds of general formula (VII) may be prepared by treatment of a compound of general formula (IX)

wherein R2 and R5 to R8 are as defined above and R represents an alkyl group with a compound of general formula (X)

wherein X is as defined above, followed by acid hydrolysis.

Compounds of general formula (IX) and (X) can be prepared by methods set out in the literature.

As a further alternative compounds of general formula (I) wherein X is a substituent in the 5position of the thiophene ring of general formula (XI)

wherein R11 to R13 are as defined above can be prepared by treatment of a compound of general formula (I) wherein X=hydrogen with an appropriate base such as butyllithium followed by a compound of general formula (XII)

wherein R11 to R13 are as defined above and W is a leaving group such as chloride, bromide or iodide.

The compounds, and their acid addition salts and N-oxides are active fungicides, particularly against the diseases Puccinia recondita, Puccinia striiformis and other rusts on wheat, Puccinia hordei, Puccinia striiformis and other rusts on barley, and rusts on other hosts e.g. coffee, apples, vegetables and ornamental plants Erysiphe graminis (powdery mildew) on barley and wheat and other powdery mildews on various hosts such as Sphaerotheca fuliginea on cucurbits (e.g.

cucumber), Podosphaera leucotricha on apples and Uncinula necator on vines Helminthosporium spp., eg. Pyrenophora teres Rhynchosporium spp. and Pseudocercosporella herpotrichoides on cereals Cercospora arachidicola on peanuts and other Cercospora species on for example sugar beet, bananas and soya beans Botrytis cinerea (grey mould) on tomatoes, strawberries, vines and other hosts Venturia inaequalis (scab) on apples.

Some of the compounds have also shown a broad range of activities against fungi in vitro. They have activity against various post-harvest diseases on fruit (e.g. Penicillium diqatatum and italicum on oranges and Gloeosporium musarum on bananas).

Further some of the compounds are active as seed dressings against: Fusarium spp., Septoria spp., Tilletia spp. (i.e. bunt, a seed borne disease of wheat), Ustilaqo spp., Helminthosporium spp. and Pseudocercosporella herpotrichoides on cereals, Rhizoctonia solani on cotton.

The compounds can move acropetally in the plant tissue. Moreover, the compounds can be volatile enough to be active in the vapour phase against fungi on the plant.

They may also be useful as industrial (as opposed to agricultural) fungicides, e.g. in the prevention of fungal attack on wood, hides, leather and especially paint films. The compounds may be used as such for fungicidal purposes but are more conveniently formulated into compositions for such usage. The invention thus provides a fungicidal composition comprising a compound of general formula (I) as hereinbefore defined, or an acid addition thereof; and, optionally, a carrier or diluent.

The invention also provides a method of combating fungi, which comprises applying to a plant, to seed of a plant, or to the locus of the plant or seed, a compound, or an acid addition salt thereof, as hereinbefore defined.

The compounds and their acid addition salts can be applied in a number of ways, for example they can be applied, formulated or unformulated, directly to the foliage of a plant, or they can be applied also to bushes and trees, to seeds or to other medium in which plants, bushes or trees are growing or are to be planted, or they can be sprayed on, dusted on or applied as a cream or paste formulation, or they can be applied as a vapour; or as slow release granules.

Application can be to any part of the plant, bush or tree, for example to 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 trees and they may also be sprayed onto vegetation using electrodynamic spraying techniques.

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

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 dustinq powders or granules comprising the active ingredient and a solid diluent or carrier, for example fillers such as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, Fuller's earth, gypsum, Hewitt's earth, 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, for example, may comprise 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 or dimethylformamide).

The compositions may also be in the form of dispersible powders, granules or grains comprising a wetting agent to facilitate the dispersion in liquids of the powder or grains which may contain also fillers and suspending agents.

The aqueous dispersions or emulsions may be prepared by dissolving the active ingredient(s) in an organic solvent optionally containing wetting, dispersing or emulsifying agent(s) and then adding the mixture to water which may also contain wetting, dispersing or emulsifying agent(s). Suitable organic solvents are ethylene dichloride, isopropyl alcohol, propylene glycol, diacetone alcohol, toluene, kerosene, methylnaphthalene, the xylenes, trichloroethylene, furfuryl alcohol, tetrahydrofurfuryl alcohol, and glycol ethers (eg. 2ethoxyethanol and 2-butoxyethanol).

The compositions to be used as sprays may also be in the form of aerosols wherein the formulation is held in a container under pressure in the presence of a propellant, eg. fluorotrichloromethane or dichlorodifluoromethane.

The compounds can be mixed in the dry state with 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 a micro-encapsulated form. They may also be formulated in biodegradable polymeric formulations to obtain a slow, controlled release of the active substance.

By including suitable additives, for example additives for improving the distribution, adhesive power and resistance to rain on treated surfaces, the different compositions can be better adapted for various utilities.

The compounds can be used as mixtures with fertilisers (eg. nitrogen-, potassium- or phosphoruscontaining fertilisers). Compositions comprising only granules of fertiliser incorporating, for example coated with, the compound are preferred.

Such granules suitably contain up to 25% by weight of the compound. The invention therefore also provides a fertiliser composition comprising the compound of general formula (I) or a salt thereof.

The compositions may also be in the form of liquid preparations for use as dips or sprays which are generally aqueous dispersions or emulsions containing the active ingredient in the presence of one or more surfactants eg. wetting agent(s), dispersing agent(s), emulsifying agent(s) or suspending agent(s); or which are spray formulations of the kind suitable for use in electrodynamic spraying techniques. The foregoing agents can be cationic, anionic or non-ionic agents. Suitable cationic agents are quaternary ammonium compounds, for example cetyltrimethylammonium bromide.

Suitable anionic agents are soaps, salts of aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), and salts of sulphonated aromatis 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 with fatty alcohols such as oleyl or cetyl alcohol, or with alkyl phenols such as octyl- or nonyl-phenol 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 with ethylene oxide, and the lecithins. Suitable suspending agents are hydrophilic colloids (for example polyvinylpyrrolidone and sodium carboxymethylcellulose), and the vegetable gums (for example gum acacia and gum tragacanth).

The compositions for use as aqueous dispersions or emulsions are generally supplied in the form of a con-centrate containing a high proportion of the active ingredient(s), and the concentrate is to be diluted with water before use. These concentrates often should be able to withstand storage for prolonged periods and after such storage be capable of dilution with water in order to form aqueous-preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional and electrodynamic spray equipment. The concentrates may conveniently contain up to 95%, suitably 10-85%, for example 25-60%, by weight of the active ingredient(s).These concentrates suitably contain organic acids (eg. alkaryl or aryl sulphonic acids such as xylenesulphonic acid or dodecyl benzenesulphonic acid) since the presence of such acids can increase the solubility of the active ingredient(s) in the polar solvents often used in the concentrates. The concentrates suitably contain also a high proportion of surfactants so that sufficiently stable emulsions in water can be obtained. After dilution to form aqueous preparations, such preparations may contain varying amounts of the active ingredient(s) depending upon the intended purpose, but an aqueous preparation containing 0.0005% or 0.01% to 10% by weight of active ingredient(s) may be used.

The compositions of this invention can comprise also other compourd(s) having biological activity, eg. compounds having similar or complementary fungicidal activity or compounds having plant growth regulating, herbicidal or insecticidal activity.

The other fungicidal compound can be, for example, one which is capable of combating ear diseases of cereals (eg. wheat) such as Septoria, Gibberella and Helminthosporium spp., seed and soil borne diseases and downy and powdery mildews on grapes and powdery mildew and scab on apple etc.

These mixtures of fungicides can have a broader spectrum of activity than the compound of general formula (I) alone; further the other fungicide can have a synergistic effect on the fungicidal activity of the compound of general formula (I). Examples of the other fungicidal compound are carbendazim, benomyl, thiophanate-methyl, thiabendazole, fuberidazole, etridazole, dichlofluanid, cymoxanil, oxadixyl, ofurace, metalaxyl, furalaxyl, benalaxyl, fosetyl aluminium, fenarimol, iprodione, procymidione, vinclozolin, penconazole, myclobutanil, R0151297, S3308, pyrazophos, ethirimol, ditalimfos, tridemorph, triforine, nuarimol, triazbutyl, guazatine, propiconazole, prochloraz, flutriafol, chlortriafol ie. the chemical l-(1,2,4-triazol-l-yl)- 2-(2,4-dichlorophenyl)hexan-2-ol, DPX H6573(1-((bis4-fluorophenyl)methylsilyl)methyl)lH-1,2,4-triazole, triadimefon, triadimenol, diclobutrazol, fenpropimorph, fenpropidine, chlorozolinate, diniconazol, imazalil, fenfuram, carboxin, oxycarboxin, methfuroxam, dodemorph, BAS 454, bitertanol, bupirimate, etaconazole, streptomycin, cypofuram, biloxazol, quinomethionate, dimethirimol, l-(2-cyano-2-methoxyimino-acetyl)-3-ethyl urea, fenapanil, tolclofos-methyl, pyroxyfur, polyram, maneb, mancozeb, captafol, chlorothalonil, anilazine, thiram, captan, folpet, zineb, propineb, sulphur, dinocap, binapactryl, nitrothalisopropyl, dodine, dithianon, fentin hydroxide, fentin acetate, tecnazene, quintozene, dichloran, copper containing compounds such as copper oxychloride, copper sulphate and Bordeaux mixture, and organomercury compounds.

The compounds of general formula (I) can be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases.

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

Plant growth regulating compounds for use in the invention compositions are compounds which control weeds or seedhead formation, or selectively control the growth of less desirable plants (e.g. grasses).

Examples of suitable plant growth regulating compounds for use with the invention compositions are the gibberellins (e.g. GA3, GA4 or GA7), the auxins (e.q. indoleacetic acid, indolebutyric acid, naphthoxyacetic acid or naphthylacetic acid), the cytokinins (e.g. kinetin, diphenylurea, benzimidazole, benzyladenine or benzylaminopurine), phenoxyacetic acids (e.g. 2,4-D or MCPA), substituted benzoic acids (e.g. triiodobenzoic acid), morphactins (e.g. chlorfluoroecol), maleic hydrazide, glyphosate, glyphosine, long chain fatty alcohols and acids, dikegulac, paclobutrazol, flurprimidol, fluoridamid, mefluidide, substituted quaternary ammonium and phosphonium compounds (e.g. chloromequat chlorphonium or mepiquatchloride), ethephon, carbetamide, methyl-3,6-dichloroanisate, daminozide, asulam, abscisic acid, isopyrimil, 1-(4- chlorophenyl)-4, 6-dimethyl-2-oxo-1,2-dihydropyridine- 3-carboxylic acid, hydroxybenzonitriles (e.g.

bromoxynil), difenzoquat, benzoylprop-ethyl 3,6dichloropicolinic acid, fenpentezol, inabenfide, triapenthenol and tecnazene.

The following Examples illustrate the invention; the temperatures are given in degrees Centigrade (0C).

EXAMPLE 1 This Example illustrates the preparation of Z and E l-[4-(cis-2,6-dimethylmorpholino)]-3-[5-(2- trimethylsilyl-thienyl)lcyclopentane hydrochloride (Compound Nos. 1 and 2 of Table I).

n-Butyllithium (25ml of a 1.6M solution in hexane, 40 mmol) was added dropwise to a stirred solution of 2-bromo-thiophene (3.9ml, 40 mmol) in dry ether (60ml) at OOC. The mixture was warmed to room temperature and after 1 hour added to anhydrous zinc bromide (4.50g, 20 mmol) in dry ether (20ml). The mixture was sonocated for 20 minutes and 2cyclopentenone (0.82g, 10 mmol) and nickel acetylacetonate (60mg) in dry ether (10 ml) were added. After 16 hours the mixture was poured into saturated aqueous ammonium chloride solution and the resultant mixture extracted with ether. The combined extracts were dried (MgSO4) and evaporated in vacuo.

Chromatography (SiO2, ethyl acetate-hexane mixtures) gave 3-(2-thienyl)-cyclopentanone (0.282g, 17%).

Hydrogen chloride in methanol (2.52 ml of a 2.5M solution, 6.4 mmol) was added dropwise to a stirred mixture of 3-(2-thienyl)cyclopentanone (0.526g, 3.2 mmol), tetrabutylammonium cyanoborohydride (1.78g, 6.4 mmol), cis-2,6-dimethylmorpholine (2.21g, 19.2 mmol) and 4A molecular sieves ( lg) in dry dichloromethane (20 ml) at room temperature under nitrogen. After 20 hours the mixture was poured into 2M sodium hydroxide solution and the resultant mixture extracted with ether. The combined extracts were washed with water, dried (MgSO4) and evaporated in vacuo. Chromatography [SiO2, ethyl acetate-hexane (20:80)] gave Z 1-[4-(cis-2,6-dimethylmorpholino)]-3- (2-thienyl)cyclopentane (0.254g, 30%) and E 1-[4 (cis-2,6-dimethylmorpholino)]-3-(2- thienyl)cyclopentane (0.192g, 23%).

n-Butyllithium (0.60ml of a 1.6M solution in hexane, 0.96 mmol) was added to a stirred solution of Z l-[4-(cis-2,6-dimethylmorpholino)]-3-(2- thienyl)cyclopentane (0.234g, 0.88 mmol) in dry tetrahydrofuran (2ml) at OOC under nitrogen. After 1 hour the mixture was cooled to -780C and trimethylsilyl chloride (0.16 ml, 0.96 mmol) added.

After 30 minutes the mixture was warmed to room temperature and ethyl acetate (1 ml) added. The mixture was poured into water (10 ml) and ether added. The mixture was filtered and the precipitate dried to give Z l-[4-(cis-2,6-dimethylmorpholino)]-3- [5-(2-trimethylsilyl-thienyl)]cyclopentane hydrochloride (0.085g, 26%).

n-Butyllithium (0.45ml of a 1.6M solution in hexane, 0.71 mmol) was added to a stirred solution of E 1-[4-(cis-2,6-dimethylmorpholino) ]-3-(2- thienyl)cyclopentane (0.172g, 0.65 mmol) in dry tetrahydrofuran (2ml) at 0 C under nitrogen. After 1 hour the mixture was cooled to -780C and trimethylsilyl chloride (0.1 ml, 0.71 mmol) added.

After 30 minutes the mixture was warmed to room temperature and ethyl acetate (1 ml) added. The mixture was poured into water (10 ml) and extracted with ether. The combined extracts were dried (MgSO4) and evaporated in vacuo to give E 1-[4-(cis-2,6 dimethylmorpholino) ]-3-[5-(2- trimethylsilylthienyl) ]cyclopentane hydrochloride (0.090g, 37%).

The spectroscopic data for the above Z and E isomers are as follows Z Isomer l-[4-(cis-2,6-Dimethylmorpholino)]-3-[5-(2- trimethyl-silylthienyl) ]cyclopentane hydrochloride.

1H NMR (CDC13, 270 MHz) : 7.07 (lH, d, J=3.8 Hz), 6.96 (lH, d, J=3.8 Hz), 4.42 (2H, m), 3.38 (4H, m), 2.64-2.01 (8H, m), 1.22 (6H, d, J=6.2 Hz) and 0.29 (9H, s).

m/s : 337 (12), 308 (7), 236 (9), 222 (7), 207 (7), 182 (14), 181 (100), 180 (38), 167 (12), 154 (18), 152 (11), 141 (36), 140 (48), 138 (8), 126 (11), 115 (12), 114 (9), 97 (8), 91 (15), 73 (41), 59 (10), 56 (12), 55 (20), 43 (10), 42 (20) and 41 (23).

E Isomer l-(4-(cis-2,6-Dimethylmorpholino)]-3-[5-(2- trimethyl-silylthienyl)lcyclopentane hydrochloride.

1H NMR (CDC13, 270 MHz) : 7.05 (lH, d, J=3 Hz), 6.86 (lH, d, J=3 Hz), 4.20 (2H, m), 3.71 (1H, m), 3.25 (2H, m), 2.50-1.50 (9H, m), 1.22 (3H, d, J=6.2 Hz), 1.20 (3H, d, J=6.2 Hz) and 0.29 (9H, s).

m/s : 337 (12), 308 (8), 236 (7), 222 (7), 207 (11), 182 (14), 181 (100), 180 (40), 167 (12), 154 (17), 152 (10), 141 (36), 140 (48), 138 (8), 126 (11), 115 (15), 91 (18), 73 (43), 56 (16), 55 (22), 45 (11), 43 (11), 42 (23) and 41 (30).

EXAMPLE 2 An emulsifiable concentrate was made up by mixing the ingredients, and stirring the mixture until all the constituents were dissolved.

Compound of Example 1 (Z form) 10% Ethylene dichloride 40% Calcium dodecylbenzenesulphate 5% "Lubrol" L 10% "Aromasol" H 35% EXAMPLE 3 A composition in the form of grains readily dispersible in a liquid, e.g. water, was prepared by grinding together the first three ingredients in the presence of added water and then mixing in the sodium acetate. The resultant mixture was dried and passed through a British Standard mesh sieve, size 44-100, to obtain the desired size of grains.

Compound of Example 1 (E form) 50% "Dispersol" T 25% "Lubrol" APN5 1.5% Sodium acetate 23.5% EXAMPLE 4 The ingredients were all ground together to produce a powder formulation readily dispersible in liquids.

Compound of Example 1 (Z form) 45% "Dispersol" T 5% "Lissapol" NX 0.5% "Cellofas" B600 2% Sodium acetate 47.5% EXAMPLE 5 The active ingredient was dissolved in a solvent and the resultant liquid was sprayed on to the granules of China clay. The solvent was then allowed to evaporate to produce a granular composition.

Compound of Example 1 (E form) 5% China clay granules 95% EXAMPLE 6 A composition suitable for use as a seed dressing was prepared by mixing the three ingredients.

Compound of Example 1 (z form) 50% Mineral oil 2% China clay 48% EXAMPLE 7 A dusting powder was prepared by mixing the active ingredient with talc.

Compound of Example 1 (E form) 5% Talc 95% EXAMPLE 8 A Col formulation was prepared by ball-milling the constituents set out below and then forming an aqueous suspension of the ground mixture with water.

Compound of Example 1 (Z form) 40% "Dispersol" T 10% "Lubrol" APN5 1% Water EXAMPLE 9 A dispersible powder formulation was made by mixing together the ingredients set out below and then grinding the mixture until all were thoroughly mixed.

Compound of Example 1 (E form)25% "Aerosol" OT/B 2% "Dispersol" A.C. 5% China clay 28% Silica 40% EXAMPLE 10 This Example illustrates the preparation of a dispersible powder formulation. The ingredients were mixed and the mixture then ground in a comminution mill.

Compound of Example 1 (Z form) 25% "Perminal" BX 1% "Dispersol" T 5% Polyvinylpyrrolidone 10% Silica 25% China clay 34% EXAMPLE 11 The ingredients set out below were formulated into a dispersible powder by mixing then grinding the ingredients.

Compound of Example 1 (E form) 25% "Aerosol" OT/B 2% "Dispersol" A 5% China clay 68% In Examples 2 to 11 the proportions of the ingredients given are by weight.

The compounds set out in Table 1 and numbered 2 to 15 can be similarly formulated as specifically described in Examples 2 to 11.

There now follows an explanation of the compositions or substances represented by the various Trade Marks mentioned above.

LUBROL L : a condensate of nonyl phenol 1 mole) with ethylene oxide (13 moles) AROMASOL H : a solvent mixture of alkylbenzenes DISPERSOL T & AC : a mixture of sodium sulphate and a condensate of formaldehyde with sodium naphthalene sulphonate LUBROL APN5 : a condensate of nonyl phenol (1 mole) with naphthalene oxide (5.5 moles) CELLOFAS B600 : a sodium carboxymethyl cellulose thickener LISSAPOL NX : a condensate of nonyl phenol (1 mole) with ethylene oxide (8 moles) AEROSOL OT/B : dioctyl sodium sulphosuccinate PERMINAL BX : a sodium alkyl naphthalene sulphonate EXAMPLE 12 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 4 cm diameter minipots. The test compounds were formulated either by bead milling with 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 on to 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./dry soil. Tween 20, to give a final concentration of 0.05%, was added when the sprays were applied to cereals.

For most of the tests the compound was applied to the soil (roots) and to the foliage (by spraying) one or two days before the plant was inoculated with the disease. An exception was the test on Erysiphe grains in which the plants were inoculated 24 hours before treatment.

Foliar pathogens were applied by spray as spore suspensions onto the leaves of test plants. After inoculation, the plants were put into an appropriate environment to allow 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 was recorded by the following grading 4 = no disease 3 = trace - 5% of disease on untreated plants 2 = 6-25% of disease on untreated plants 1 = 26-59% of disease on untreated plants 0 = 60-100% of disease on untreated plants The results are shown in Table II.

TABLE I@

COMPOUND PUCCINIA ERYSIPHE VENTURIA CERCOSPORA NUMBER RECONDITA GRAMINIS INAEQUALIS APACHIDICOLA (WHEAT) (BARLEY) (APPLES) (PEANUTS) 1 (Z) 1 4 4 4 2 (E) 0 4 4 4

Claims

What we -claim is 1. Compounds having the general formula

and stereoisomers thereof, wherein R1 to R8 each represents a hydrogen atom or an alkyl or haloalkyl group containing from 1 to 4 carbon atoms, R9 and R10 each represents an alkyl or haloalkyl group containing from 1 to 4 carbon atoms or R9 and R10 together with the adjacent nitrogen atom form a heterocyclic ring which may optionally contai-n an additional heteroatom, X represents a hydrogen atom, a halogen atom or an alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy or aryloxy group, or a

group wherein R11 to R13 can be an alkyl group containing from 1 to 4 carbon atoms or a phenyl group; and acid addition salts and N-oxides thereof.
2. A compound as claimed in claim 1 wherein R1 to R8 represents hydrogen or a C14 alkyl group; tJR9R10 represents a piperidine, morpholine, thio-morpholine, pyrollidine or piperazine ring optionally substituted with one or two C14 alkyl or phenyl groups and X is trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, phenyldimethylsilyl, C14 alkyl or halogen at the 3-, 4- or 5- positions of the thiophene ring
3. A compound as claimed in claim 2 wherein R1, R21 R6 and R7 are hydrogen or methyl; R3, R4, R5 and R8 are hydrogen; NR9R10 is a morpholine or piperidine ring optionally substituted with one or two methyl groups; and X is trimethylsilyl, butyl, propyl or chlorine at the 5-position of the thiophene ring.
4. A process for preparing a compound of formula (I) as claimed in any of claims 1 to 3 wherein R1 to R3, R5 to R10 and X are as defined and R4 is hydrogen which comprises reductive amination of compounds of general formula (II) :

wherein R1 to R3, R5 to R8 and X are as defined in any of claims 1 to 3 and R4 is hydrogen with an amine of general formula (III) HNR9R10 (III) wherein R9 and R10 are as defined in any of claims 1 to 3 with a reducing agent, for example formic acid, sodium cyanoborohydride or tetrabutylammonium cyanoborohydride.
5. A process for preparing compounds of general formula (II) as defined in claim 4 which comprises treatment of enones of the general formula (IV)

wherein R11 R2 and R5 to R8 are as defined in any of claims 1 to 3 with an organozinc reagent of general formula (V)

wherein X is as defined in any of claims 1 to 3 in the presence of a catalytic amount of nickel acetyl-acetonate.
6. A process for preparing compounds of general formula (II) as defined in claim 4 which comprises treatment of a compound of general formula (VII)

wherein R2, R5 to R8 and X are as defined in claim 4 with an organocuprate reagent of general formula (VIII) (R1)2CuLi (VIII) wherein R1 is as defined in claim 4.
7. A process as claimed in claim 6 wherein the compounds of general formula (VII) are prepared by treatment of a compound of general formula (Ix)

wherein R2 and R5 to R8 are as defined in claim 6 and R represents an alkyl group with a compound of general formula (X) :

wherein X is as defined in claim 6, followed by acid hydrolysis.
8. A process for preparing compounds of general formula (I) wherein X is a substituent in the 5 position of the thiophene ring and has the general formula (XI)

wherein R11 to R13 are as defined in claim 1 which comprises treatment of a compound of general formula (I) wherein X is hydrogen with an appropriate base such as butyllithium followed by a compound of general formula (XII)

wherein R11 to R13 are as defined in claim 1 and W is a leaving group such as chlorine, bromine or iodine.
9. A fungicidal composition comprising a compound, or a salt thereof, as claimed in any of claims 1 to 3, and, optionally, a carrier or diluent.
10. A method of combatting fungi which comprises applying to a plant, to seed of a plant, or to the locus of the plant or seed, a compound, or salt thereof, as claimed in any of claims 1 to 3 or a composition as claimed in claim 9.