WO1994001403A1

WO1994001403A1 - Piperidine derivatives

Info

Publication number: WO1994001403A1
Application number: PCT/EP1993/001777
Authority: WO
Inventors: Paul Andrew Carter
Original assignee: Shell Internationale Research Maatschappij BV
Current assignee: Shell Internationale Research Maatschappij BV
Priority date: 1992-07-08
Filing date: 1993-07-06
Publication date: 1994-01-20
Anticipated expiration: 1995-01-08
Also published as: ZA934874B; CN1085384A; AU4566093A

Abstract

The invention provides a method of combating fungi using a piperidine derivative of general formula (I) or an acid-addition salt thereof, in which R1 represents an aryl group which may be substituted by one or more substituents, R2 represents a hydrogen atom or an alkyl or phenyl group, R3 represents a hydrogen atom or an alkyl or phenyl group, R4 represents an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heterocyclyl group, m represents an integer from 0 to 3, and n represents an integer from 0 to 2. Certain of the piperidine derivatives are novel and the invention further relates to the preparation of these piperidine derivatives and intermediates, compositions containing these compounds and their use as fungicides for the control of phytopathogenic fungi.

Description

PIPERIDINE DERIVATIVES

The present invention relates to a method of combating fungi using certain piperidine derivatives, some of which are novel, processes for their preparation, compositions containing such compounds and their use as fungicides for the control of phytopathogenic fungi.

In DE-A-3614907 piperidine derivatives of the general formula

are disclosed, in which general formula R represents a C. .. alkyl, C₂_₂₀ alkoxyalkyl, C₂.₂o hydroxyalkyl, C_{3 12} cycloalkyl, C^ _2Q alkylcycloalkyl, C, „» cycloalkylalkyl, aryl, haloaryl, C_ aralkyl, C. ₂₀ haloaralkyl or C_{? 20} aryloxyalkyl, m is 1 or 2 and n is 0 or 1. Compounds in which m is 2, that is piperidine derivatives substituted at the 1- and 4- positions, and n is 0 are said to be especially preferred. In addition, WO-A-9202502 describes the preparation of

N-n-pentyl-4- [2-( -fluorophenyl)ethyl]piperidine hydrobromide and N-n-pentyl-4-(3-phenylpropyl)piperidine hydrochloride as pharmaceutical compounds having activity as cerebral calcium blockers. J63179850 describes the preparation of N-(2,3-dihydroxy- 3,7,ll-trimethyldodec-l-yl)-4-(2-phenylethyl)piperidine as an allergy inhibitor and brain function improver. Synth. Commun. , 88, Vol. 18(12), pp. 1331-7 discloses N-methyl-4-(3-phenylpropyl)- piperidine and Fresenius' Z. Anal. Chem. , 85, Vol. 322(4), pp. 391-6 discloses the conjugate acid of this compound. FR M 2239 (CA. 60:15839 d) discloses N-[2-(dimethylamino)ethyl)-4-(2-phenyl- ethyl)piperidine and its dihydrochloride, the latter being useful in the treatment of atherosclerosis. US 4033971 describes the preparation of N-methyl-4- [2-(2-methylphenyl)ethyl]piperidine. FR 1489505 describes the preparation of N-(2-hydroxyethyl)-4-(3- phenylpropyl)piperidine hydrochloride and N-(2-chloroethyl)-4-(3- phenylpropyl)piperidine hydrochloride and US 3352873 describes the preparation of N-(4-hydroxybutyl)-4-(3-phenylpropyl)piperidine and N-(2-hydroxyethyl)-4-(3-phenylpropyl)piperidine. However, there is no indication in any of the above documents that any of the compounds disclosed therein exhibit fungicidal activity.

It has now been found that certain new piperidine derivatives show excellent fungicidal activity against certain phytopathogenic fungi, particularly against Erysiphe graminis.

The present invention therefore relates to a method of combating fungi at a locus which comprises treating the locus with _a compound of the general formula

or an acid-addition salt thereof, in which

R represents an aryl group which may be substituted by one or more substituents,

2 R represents a hydrogen atom or an alkyl or phenyl group, represents a hydrogen atom or an alkyl or phenyl group, R represents an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heterocyclyl group, m represents an integer from 0 to 3, and n represents an integer from 0 to 2. The locus to be treated especially comprises plants subject to or subjected to fungal attack, seeds of such plants or the medium in which the plants are growing or are to be grown.

The invention especially relates to a method in which R represents an optionally substituted aromatic hydrocarbyl group. R in particular represents a phenyl or naphthyl group, optionally substituted by one or more halogen atoms or hydroxy, nitro, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, arylamino, formyl, alkylcarbonyl, alkoxycarbonyl, carboxyl, phenyl, halophenyl or phenoxy groups. Preferably R represents a phenyl group optionally substituted by one or more fluorine, chlorine or bromine atoms, cyano, C , alkyl, C. haloalkyl, C. , alkoxy, C , haloalkoxy, C , alkylamino, di-C. alkylamino, C. , alkoxycarbonyl, or phenyl groups. The invention especially relates to a method in which R 2 and

3 R represent hydrogen or a C , alkyl group, more especially a

2 3 methyl group. Preferably R and R represent hydrogen.

The invention further especially relates to a method in which 4 R represents an alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, naphthyl, pyridyl, thienyl, pyrimidyl or furyl group, each group optionally substituted by one or more substituents selected from halogen atoms or nitro, cyano, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, arylamino, formyl, alkylcarbonyl, alkoxycarbonyl, carboxyl, phenyl, halophenyl or

4 phenoxy groups. Preferably R represents a C .„ alkyl, C alkenyl, C _ alkynyl, C, _g cycloalkyl, phenyl, pyridyl or thienyl group, each group being optionally substituted by one or more substituents selected from fluorine, chlorine or bromine atoms or C alkyl, C , haloalkyl, C. , alkoxy, C , haloalkoxy, C alkylamino, di-C. , alkylamino, C alkylcarbonyl, C alkoxycarbonyl, or phenyl groups. More preferably R represents a C, _g alkyl, C _ alkenyl, C__g alkynyl, C, , cycloalkyl, naphthyl, phenyl, pyridyl or thienyl group, optionally substituted by one or more substituents selected from halogen atoms, especially fluorine, chlorine and bromine atoms, nitro, cyano, C , alkyl, C. . haloalkyl, C. , alkoxy, C. , alkylcarbonyl, C. , alkoxycarbonyl, phenyl, halophenyl, and phenoxy groups.

The invention especially relates to a method in which m represents 0, 1 or 2.

The alkylene group which connects R and the piperidine ring may optionally be substituted by one or more halogen atoms or one or more C , alkyl groups, especially methyl or ethyl groups. Suitably the chain is substituted by a fluorine, chlorine or bromine atom or a methyl group.

A particularly preferred sub-group of compounds of the general formula I that may be used in the method of the invention is that in which R represents a phenyl, butylphenyl, methylphenyl,

2 3 fluorophenyl, chlorophenyl or bromophenyl group, R and R

4 represent a hydrogen atom, R represents a phenyl, fluorophenyl, chlorophenyl, dichlorophenyl, bromophenyl, nitrophenyl, methylphenyl, butylphenyl, methoxyphenyl, methoxycarbonylphenyl, trifluoromethylphenyl, biphenyl, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl or octyl group and m represents 0, 1 or 2.

Alkyl as substituent or as part of other substituents, such as alkoxy, alkoxycarbonyl etc. , for example may contain up to 12, preferably up to 6, and especially up to 4, carbon atoms and includes the following straight-chain or branched groups depending on the number of carbon atoms indicated: methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, etc. as well as their isomers such as isopropyl, isobutyl, tertiary-butyl, isopentyl. Halogen includes fluorine, chlorine, bromine or iodine, especially fluo¬ rine, chlorine and bromine. Cycloalkyl may contain 3 to 8, prefer¬ ably 3 to 6, carbon atoms and includes the following substituents depending on the number of carbon atoms indicated: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl etc. An aryl group may be any aromatic hydrocarbon group, especially a phenyl or naphthyl group. Generally, substituents of alkyl, alkenyl, cycloalkyl and phenyl etc. preferably are halogen, methoxy, nitro, amino, cyano and, in the case of cycloalkyl and phenyl, also methyl and trifluoromethyl. Heterocyclyl groups are especially 5- or 6-membered heterocycles, preferably saturated or unsaturated 5- or 6-membered heterocycles containing one to four of the same or different heteroatoms such as nitrogen, oxygen or sulphur.

When any of the foregoing substituents are designated as being optionally substituted, the substituent groups which are optionally present may be one or more of those customarily employed in the development of fungicidal compounds and/or the modification of such compounds to influence their structure/activity, persistence, penetration or other properties. Specific examples of such substituents, unless otherwise stated, include, for example, halogen atoms, nitro, cyano, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, carbamoyl, alkylamido, phenyl, halophenyl and phenoxy groups.

The compounds of formula I may form acid addition salts with a variety of acids. However, acid addition salts with acids such as aliphatic and aromatic carboxylic acids, such as acetic, lauric, benzoic, oxalic, lactic, and mandelic acids, aliphatic and aromatic sulphonic acids, such as dodecylbenzenesulphonic acid, saccharin, _an mineral acids such as phosphonic and hydrochloric acid, are especially preferred. Preferred acid addition salts are plant-physiologically acceptable salts.

It should be appreciated that some of the compounds of formula

I are capable of existing as different geometric isomers and diastereomers. The invention includes both the individual isomers and mixtures of isomers.

Certain of the compounds of formula I as defined above are novel. Accordingly, the invention also provides a compound of the general formula I as defined above with the provisos that:-

(i) when m is 0, n is 0 and R represents a 4-fluorophenyl 4 group, then R does not represent a n-pentyl group;

(ii) when m is 0, n is 0 and R represents a phenyl group, 4 then R does not represent a 2-(dimethylamino)ethyl or

2,3-dihydroxy-3,7,11-trimethyldodec-1-yl group; (iii) when m is 0, n is 0 and R represents a 2-methylphenyl

4 group, then R does not represent a methyl group; and

(iv) when m is 0, n is 1 and R represents a phenyl group, 4 then R does not represent a methyl, 2-chloroethyl, 2-hydroxyethyl,

4-hydroxybutyl or n-pentyl group. The present invention also provides a process for the preparation of a compound of the general formula I as defined above or an acid addition salt thereof which comprises reacting a compound of the general formula

in which R and n are as defined above, with a compound of the general formula

2 3 4 in which m, R , R and R are as defined above and X represents a leaving group, and, if desired, reacting the compound of the general formula I so obtained with a suitable acid to form an acid-addition salt thereof.

Preferably the leaving group is a halogen, especially a chlorine or bromine atom or a sulphonate group, such as a methyl sulphonate or toluenesulphonate group.

The process of the present invention is conveniently carried out in the presence of a solvent. Suitable solvents include ethers, particularly tetrahydrofuran, alcohols, particularly ethanol, and dimethylformamide. The reaction is suitably carried out at a temperature between 0 °C and 160 °C, the preferred reaction temperature being between 20 °C and 120 °C It is also preferred that the reaction is carried out in the presence of a base, such as potassium carbonate. Compounds of the general formula II in which R is as defined above and n represents 0 may be conveniently prepared by reaction of an optionally substituted bromo- or iodo-phenyl compound with (4-)vinyl substituted pyridine in the presence of a suitable noble and/or transition metal catalyst, preferably a palladium catalyst, followed by hydrogenation of the obtained product. These reactions are described by R.F. Heck in Org. Reactions, 1982, 2_7, 345 and in Comprehensive Organic Chemistry, 1991, vol. 8, 497, Eds. B.M. Trost and I. Fleming, Pergamon Press. Alternatively, compounds of the general formula II in which R is as defined above and n represents 0 may be prepared by reacting an appropriate benzaldehyde with 4-picoline and acetic acid anhydride, followed by hydrogenation of the product so obtained.

Compounds of the general formula II in which R is as defined above and n represents 1 may be obtained by hydrogenation of the 0 commercially available pyridines. Alternatively, compounds of the general formula II in which R is as defined above and n represents

1 may be prepared by reaction of an appropriate acetophenone with 4-pyridine carboxaldehyde in the presence of, for example, piperidine and acetic acid, followed by hydrogenation of the

1 product so obtained.

Compounds of the general formula II in which R is as defined above and n represents 2 may be conveniently prepared by reaction of (4-)vinyl substituted pyridines with an optionally substituted 2-bromo or 2-iodo styrene compound, followed by reduction of the

20 obtained pyridyl-diene. These reactions are described by R.F. Heck in Org. Reactions, 1982, _, 345 and in Comprehensive Organic Chemistry, 1991, vol. 8, 497, Eds. B.M. Trost and I. Fleming, Pergamon Press.

Compounds of the general formula II in which R represents a

25 group which is chemically stable to hydrogenation may be prepared as described above. However, if R represents a group which is susceptible to hydrogenation, compounds of formula II may, for instance, be conveniently prepared from compounds of formula II in which R represents an amino-substituted aryl group via a Sandmeyer

^J" reaction. For instance, a compound of formula II in which R represents an aminophenyl group may be reacted with sodium nitrite in the presence of a mineral acid, such as hydrochloric, hydrobromic or tetrafluoroboric acid, in aqueous solution to form a diazonium salt which is then reacted with an appropriate copper (I)

".5 salt, such as copper (I) fluoride, copper (I) bromide, copper (I) cyanide etc. , to form a compound of formula II in which R represents a fluorophenyl, bromophenyl, cyanophenyl etc. group. Other compounds of formula II may then be formed by manipulation of the cyanophenyl group in the compound of formula II where R represents a cyanophenyl group using processes analogous to known processes. Compounds of formula II in which R represents an aminophenyl group may be prepared by reacting a compound of formula II in which R represents a nitrophenyl group with a suitable reducing agent, such as hydrogen with a palladium or charcoal 1 catalyst. Compounds of formula II in which R represents a nitrophenyl group may be prepared as previously described.

Compounds of formula III are known compounds or can be prepared by processes analogous to known processes.

The invention also provides fungicidal compositions comprising at least one of the compounds according to general formula I or an acid addition salt thereof, as well as methods of combating fungi at a locus comprising treatment of the locus with a compound of formula I or an acid addition salt thereof as defined hereinbefore, or with a composition as defined in this specification.

The fungicidal composition comprises a carrier and, as active ingredient, a compound of the general formula I or an acid addition salt thereof.

A method of making such a composition is also provided, which comprises bringing a compound of the general formula I as defined above or an acid addition salt thereof into association with at least one carrier. Such a composition may contain a single compound or a mixture of several compounds of the present invention. It is also envisaged that different isomers or mixtures of isomers may have different levels or spectra of activity and thus compositions may comprise individual isomers or mixtures of isomers.

The invention further relates to the use as a fungicide of a compound of formula I as defined hereinbefore or a composition as defined hereinbefore.

A composition according to the invention preferably contains from 0.5 to 95% by weight of active ingredient. A carrier in a composition according to the invention is any material with which the active ingredient is formulated to facilitate application to the locus to be treated, which may for example be a plant, seed or soil, or to facilitate storage, transport or handling. A carrier may be a solid or a liquid, including a material which is normally gaseous but which has been compressed to form a liquid, and any of the carriers normally used in formulating fungicidal compositions may be used.

Suitable solid carriers include natural and synthetic clays and silicates, for example natural silicas such as diatomaceous earths; magnesium silicates, for example talcs; magnesium aluminium silicates, for example attapulgites and vermiculites; aluminium silicates, for example kaolinites, montmorillonites and micas; calcium carbonate; calcium sulphate; ammonium sulphate; synthetic hydrated silicon oxides and synthetic calcium or aluminium silicates; elements, for example carbon and sulphur; natural and synthetic resins, for example coumarone resins, polyvinyl chloride, and styrene polymers and copolymers; solid polychlorophenols; bitumen; waxes, for example beeswax, paraffin wax, and chlorinated mineral waxes; and solid fertilisers, for example superphosphates.

Suitable liquid carriers include water; alcohols, for example isopropanol and glycols; ketones, for example acetone, methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone; ethers; aromatic or araliphatic hydrocarbons, for example benzene, toluene and xylene; petroleum fractions, for example, kerosine and light mineral oils; chlorinated hydrocarbons, for example carbon tetrachloride, perchloroethylene and trichloroethane. Mixtures of different liquids are often suitable.

Fungicidal compositions are often formulated and transported in a concentrated form which is subsequently diluted by the user before application. The presence of small amounts of a carrier which is a surface-active agent facilitates this process of dilution. Thus preferably at least one carrier in a composition according to the invention is a surface-active agent. For example the composition may contain at least two carriers, at least one of which is a surface-active agent.

A surface-active agent may be an emulsifying agent, a dispers¬ ing agent or a wetting agent; it may be nonionic or ionic. Exam- pies of suitable surface-active agents include the sodium or calcium salts of polyacrylic acids and lignin sulphonic acids; the condensation products of fatty acids or aliphatic amines or amides containing at least 12 carbon atoms in the molecule with ethylene oxide and/or propylene oxide; fatty acid esters of glycerol, ° sorbitol, sucrose or pentaerythritol; condensates of these with ethylene oxide and/or propylene oxide; condensation products of fatty alcohol or alkyl phenols, for example p-octylphenol or £-octylcresol, with ethylene oxide and/or propylene oxide; sulphates or sulphonates of these condensation products; alkali or alkaline earth metal salts, preferably sodium salts, of sulphuric or sulphonic acid esters containing at least 10 carbon atoms in the molecule, for example sodium lauryl sulphate, sodium secondary alkyl sulphates, sodium salts of sulphonated castor oil, and sodium alkylaryl sulphonates such as dodecylbenzene sulphonate; and ° polymers of ethylene oxide and copolymers of ethylene oxide and propylene oxide.

The compositions of the invention may for example be formulated as wettable powders, dusts, granules, solutions, emulsifiable concentrates, emulsions, suspension concentrates and 5 aerosols. Wettable powders usually contain 25, 50 or 75% w of active ingredient and usually contain in addition to solid inert carrier, 3-10% w of a dispersing agent and, where necessary, 0-10% w of stabiliser(s) and/or other additives such as penetrants or stickers. Dusts are usually formulated as a dust concentrate 0 having a similar composition to that of a wettable powder but without a dispersant, and may be diluted in the field with further solid carrier to give a composition usually containing h-10% w of active ingredient. Granules are usually prepared to have a size between 10 and 100 BS mesh (1.676 - 0.152 mm), and may be manufactured by agglomeration or impregnation techniques. Generally, granules will contain 4-75% w active ingredient and

0-10% w of additives such as stabilisers, surfactants, slow release modifiers and binding agents. The so-called "dry flowable powders" consist of relatively small granules having a relatively high . concentration of active ingredient. Emulsifiable concentrates usually contain, in addition to a solvent and, when necessary, co-solvent, 1-50% w/v active ingredient, 2-20% w/v emulsifiers and

0-20% w/v of other additives such as stabilisers, penetrants and corrosion inhibitors. Suspension concentrates are usually compounded so as to obtain a stable, non-sedimenting flowable product and usually contain 10-75% w active ingredient, 0.5-15% w of dispersing agents, 0.1-10% w of suspending agents such as protective colloids and thixotropic agents, 0-10% w of other additives such as defoamers, corrosion inhibitors, stabilisers, penetrants and stickers, and water or an organic liquid in which the active ingredient is substantially insoluble; certain organic solids or inorganic salts may be present dissolved in the formulation to assist in preventing sedimentation or as anti-freeze agents for water.

Aqueous dispersions and emulsions, for example compositions obtained by diluting a wettable powder or a concentrate according to the invention with water, also lie within the scope of the invention. The said emulsions may be of the water-in-oil or of the oil-in-water type, and may have a thick 'mayonnaise' like consistency.

The composition of the invention may also contain other ingredients, for example other compounds possessing herbicidal, insecticidal or fungicidal properties.

Of particular interest in enhancing the duration of the protective activity of the compounds of this invention is the use of a carrier which will provide a slow release of the fungicidal compounds into the environment of the plant which is to be protected. Such slow-release formulations could, for example, be inserted in the soil adjacent to the roots of a vine plant, or could include an adhesive component enabling them to be applied directly to the stem of a vine plant.

The present invention still further provides the use as a fungicide of a compound of the general formula I as defined above or a composition as defined above, especially the use as a fungicide against fungicidal diseases in cereals.

The present invention is of wide applicability in the protection of crop plants against fungal attack. Typical crops which may be protected include cereals, especially wheat and barley, rice, vines, potatoes, tomatoes, pome fruit, especially apples, and cucumber. The duration of protection is normally dependent on the individual compound selected, and also a variety of external factors, such as climate, whose impact is normally mitigated by the use of a suitable formulation. The compounds of the general formula II and the acid addition salt thereof also exhibit fungicidal activity. For instance, the compounds of the general formula II in which R represents phenyl or t-butyl phenyl and n represents 2 and 0 respectively show good activity against Plasmopara viticola and Venturia inaequalis. Accordingly, the present invention also relates to the compounds of the general fomula II or the acid addition salts thereof and to fungicidal compositions containing one or more compounds of the general formula II or the acid addition salts thereof, as well as to the use of the compounds of general formula II or the acid addition salts thereof or compositons containing these compounds as fungicides. The preferred embodiments for R and n correspond with the preferred embodiments for R and n in the general formula I as defined hereinafter. Also the other definitions with respect to the compounds of the general Formula II correspond with the other definitions with respect to the compounds of the general Formula I, including the acid addition salts, the isomers, the compositions, the method of combating fungi and the use.

The invention is further illustrated by the following examples. Example 1

Preparation of N- (p-chlorobenzyl) -4- (2 ' -phenylethyl) piperidine

(R^phenyl ; n_°0 ; R²-R³-H; m-l ;R -4-Cl phenyl)

(i) Preparation of 2-phenyl-l-(4'-pyridyl)ethylene

A mixture of bromobenzene (47.lg, 0.3 mol) , 4-vinylpyridine (41.Og, 0.39 mol), palladium acetate (0.67g, 3 mmol), triphenylphosphine (1.6g, 6 mmol), triethylamine (200 ml) and dimethylformamide (200 ml) was heated under reflux, with stirring for 10 days. The volatiles were then distilled off in vacuo and the residue partitioned between ethyl acetate and water, insoluble material was filtered off and discarded. The aqueous phase was extracted with ethyl acetate and the combined organic phases washed with brine and dried (MgSO, ) . Evaporation in vacuo afforded a brown solid which was recrystallised from ethyl acetate to afford the product (13.8g) as beige crystals. M.pt. 129 ^βC Analysis: Calc. C86.2; H:6.1; N:7.7% Found C88.0; H:6.3; N:8.0% (ii) Preparation of 4-(2'-phenylethyl)piρeridine

The above pyridine (13.8g, 76 mmol) in ethanol (110 ml) containing cone, hydrochloric acid (10 ml) and rhodium on charcoal (5%) was hydrogenated under Parr conditions at 60"C until hydrogen uptake ceased. The resulting suspension was filtered and evaporated ij vacuo. The resulting salt was taken up in 2N NaOH and the solution was extracted with ethyl acetate (x3) . The combined extracts were washed with brine, dried (MgSO, ) and evaporated ijj vacuo. The resulting product was purified by flash chromatography (on silica gel, ethyl acetate:methanol:triethylamine - 8:1:1 as eluant) being obtained as an oil, 11.8g. Analysis: Calc. C82.5; H.10.1; N:7.4% Found C81.8; H:10.4; N:7.3%

(iii) Preparation of N-(p-chlorobenzyl)-4-(2*-phenylethyl)- piperidine A mixture of the above piperidine (1.9g, 10 mmol), p-chlorobenzylchloride (1.6g, 10 mmol), potassium carbonate (1.8g, 13 mmol) and ethanol (40 ml) was refluxed with stirring for 64 hrs. The reaction mixture was then cooled and water added followed by ethyl acetate extraction (3x). The combined extracts were washed with brine, dried (MgSO, ) and evaporated in vacuo. Purification by flash chromatography (silica, toluene:acetone - 9:1 as eluant) afforded the product as a pale orange oil which slowly crystallised. M.pt. 64-65°C

Analysis: Calc. C76.5; H:7.7; N:4.5% Found C77.0; H:7.5; N:4.4% Example 2

Preparation of N-(p-chlorobenzyl)-4-(3'-phenylpropyl)piperidine (R^phenyl; n-1; R²-R³-H; m-1; R⁴-4-Cl phenyl) (i) Preparation or 4-(3'-phenylpropyl)piperidine

4-(3' -phenylpropyl)pyridine (20g) in ethanol (200 ml) containing cone, hydrochloric acid (10 ml) and platinum on charcoal (10%, 2g) . was hydrogenated at 50°C under Parr conditions. When hydrogen uptake ceased the suspension was filtered and the filtrate evaporated in vacuo. The resulting solid was partitioned between 30% NaOH and diethyl ether and the aqueous phase further extracted with diethyl ether (x3). The combined organic extracts were washed with brine, dried (MgSO, ) and evaporated to afford the product (19.6g) as a pale yellow liquid, (ϋ) Preparation of N-(p-chlorobenzyl)-4-(3'-phenylpropyl)- piperidine

The above piperidine (26.4g, 0.13 mol), p-chlorobenzyl chloride (20.4g, 0.13 mol), potassium carbonate (23.5g, 0.17 mol) in ethanol (300 ml) were refluxed with stirring for 112 hrs. Work up was as in Example 1 (iii), though the product was purified by recrystallisation from isopropanol, white solid (25.3g), M.pt. 54-55°C

Analysis: Calc. C76.9; H:8.0; N:4.3% Found C76.7; H:8.0; N:4.8% Example 3

Preparation of N-(2' -phenylethyl)-4- \ 2 ' -(p-t-butylphenyl)ethyll - piperidine

(R¹-4-C(CH₃)_:.phenyl: n=0; R²-R³-H; m 2; R⁴-ψhenyl) (i) Preparation of 2-(p-t-butylphenyl)-1-(4'-pyridyl)ethylene hydrochloride

A mixture of p-t-butylbenzaldehyde (25g, 0.15 mol), 4-picoline (14g, 0.15 mol) and acetic acid anhydride (28.3 ml, 0.30 mol) was refluxed for 19 hrs. Upon cooling a solid separated which was collected by filtration, dissolved in chloroform and washed with IN HC1. The organic phase was dried (MgSO.) and evaporated in vacuo giving a residue which, when washed with cold ethyl acetate, afforded the product as brown/yellow crystals (34g) . M.pt. 245°C (dec) Analysis: Calc. C74.6; H:7.4; N:5.1%

Found C73.2; H:7.3; N:5.1% (ii) Preparation of 4- f2'-(p-t-butylphenyl)ethyl1piperidine

The above pyridine (20g, 73 mmol) in ethanol (250 ml) containing cone, hydrochloric acid (10 ml) and palladium on charcoal (10%, 3g) and rhodium on charcoal (5%, 3g) were hydrogenated under Parr conditions at 50°C until uptake ceased. After filtration and evaporation in vacuo the residue was taken up in 20% NaOH and extracted with diethyl ether (x3) . The organic extracts were dried (MgSO, ) , evaporated in vacuo and the residue purified by flash column chromatography (silica, ethyl acetate:methanol: triethylamine - 8:2:0.5) affording the product as brown crystals, 9.8g. M.pt. 43-44°C Analysis: Calc. C83.2; H:ll.l; N 5.7% Found C82.8; H.ll.l; N 5.5% (iii) Preparation of N-(2'-phenylethyl)-4-f2'-(p-t-butylphenyl)- ethyl]piperidine A mixture of the above piperidine (1.5g, 6 mmol), 2-bromoethylbenzene (l.llg, 6 mmol), potassium carbonate (l.llg, 8 mmol) in ethanol (50 ml) was refluxed for 20 hrs with stirring. After cooling the ethanol was evaporated and the residue taken up in ethyl acetate and water. The organic phase was dried (MgSO.) and evaporated in vacuo to afford the product which was purified by flash column chromatography (silica, petroleum ether: ethyl acetate 9:1 as eluant), yellow crystals, 0.6g. M.pt. 97-98°C. Analysis: Calc. C78.2; H:8.9; N:3.7%

Found C:79.2; H:9.2; N:4.0% Example 4

Preparation of N-(p-chlorobenzyl)-4-(4' -phenylbutyl)piperidine (R^phenyl; n-2: R²-R³-H; m-1; R -4-Cl phenyl) (i) Preparation of 4-phenyl-l-(4'-pyridyl)buta-l,3-diene

A mixture of bromostyrene (9.15g, 50 mmol), 4-vinylpyridine (6.83g, 65 mmol), palladium acetate (O.llg, 0.5 mmol), triphenylphosphine (0.26g, 1 mmol), triethylamine (34 ml) and dimethylformamide (34 ml) was heated under reflux for 18 hrs. The reaction mixture was then evaporated j^ vacuo and the residue partitioned between ethyl acetate and water. The organic extract was dried (MgSO, ) and evaporated ij vacuo affording the crude product. This was recrystallised from isopropanol giving light yellow crystals, 4.3g. M.pt. 156-158^βC Analysis: Calc. C86.9; H:6.3; N:6.8%

Found C:87.4; H:6.6; N:6.6% (ii) Preparation of 4-(4' -phenylbutyl)piperidine

The above pyridine (3g, 14 mmol) in ethanol (60 ml) containing cone, hydrochloric acid (2 ml), palladium on charcoal (10%, 1.5g) and rhodium on charcoal (5%, 1.5g) was hydrogenated at 50^βC, under Parr conditions until hydrogen uptake ceased. The reaction mixture was then filtered and evaporated in vacuo and the residue taken up in 20% NaOH and extracted with diethyl ether (x3) . Evaporation followed by flash column chromatography (silica, ethyl acetate:methanol: riethylamine - 8:2:0.5 as eluant) afforded the product as a yellow oil, 1.8g.

Analysis: Calc. C82.9; H:10.7; N:6.4% Found C76.8; H:10.3; N:6.0% (iii) Preparation of N-(p-chlorobenzyl)-4-(4' -phenylbutyl)- piperidine

A mixture of the above piperidine (1.5g, 7 mmol), p-chlorobenzyl chloride (1.13g, 7 mmol), potassium carbonate (1.30g, 9 mmol) in ethanol (50 ml) was heated under reflux for 24 hrs. After evaporation of the ethanol, the residue was taken up in ethyl acetate and water. The organic phase was dried (MgSO, ) and evaporated in vacuo. Purification by flash column choromatography (silica, petroleum ether: ethyl acetate - 9:1 as eluant) afforded the product as a yellow oil, 1.4g. Analysis: Calc. C77.3; H:8.3; N:4.1% Found C76.7; H:8.4; N:4.1% Example 5

Preparaton of N-(p-chlorobenzyl)-4- [2' -(p-bromophenyl)ethyl] - piperidine R-^-Br phenyl; n-0; R²-R³-H; n-1; R -4-Cl phenyl) (i) Preparation of 2-( -nitrophenyl)-1-(4' -pyridyl)ethylene hydrochloride.

A mixture of 4-picoline (37.3g, 0.4 mol) and 4-nitrobenzaldehyde (60.5g, 0.4 mol) in acetic acid anhydride (40.8g, 0.4 mol) was refluxed for 19 hours. Upon cooling a solid separated out which was collected by filtration, dissolved in trichloromethane and washed with IN HC1. The organic phase was dried (MgSO.) and evaporated in vacuo producing a residue which, when washed with cold ethyl acetate, gave 52.6g 2-(p-nitrophenyl)- 1-(4' -pyridyl)ethylene hydrochloride as red crystals. M.pt. 161-164°.

Analysis: Calc. C: 69.0; H: 4.5; N: 12.4% Found C: 68.4; H: 4.5; N: 12.1% (ii) Preparation of 4-f2'-(p-aminophenyl)ethyl] iperidine monohydrate

2-(p-Nitrophenyl)-l-(4' -ρyridyl)ethylene hydrochloride (20g, 76 mmol) obtained in (i) above in ethanol (250 ml) containing cone, hydrochloric acid (10 ml) and palladium on charcoal (10%, 3g) and rhodium on charcoal (5%, 3g) were hydrogenated under Parr conditions at 50°C until uptake ceased. After filtration and evaporation in vacuo, the residue was taken up in 20% NaOH and extracted with diethyl ether (x3) . The organic extracts were dried (MgSO, ) , evaporated in vacuo and the residue purified by flash column chromatography silica, ethyl acetate:methanol:triethylamine - 8:2:0.5) to give 16.Og 4- [2' -(p-aminophenyl)ethyl]piperidine monohydrate as beige crystals, M.pt. 230-233°C Analysis: Calc. C70.2; H:10.0; N:12.6%

Found C70.8; H: 9.5; N:12.7% (iii) Preparation of 4-f2' -(p-bromophenyl)ethyl]piperidine hydrochloride A solution of sodium nitrite (2.5g, 36 mmol) in water (30 ml) was added dropwise to a solution of the 4- [2' -(p-aminophenyl)- ethyl]piperidine monohydrate (6.0g, 30 mmol) obtained in (ii) above in 50% hydrobromic acid (40 ml) at 0°C After 30 minutes, the reaction mixture was added dropwise to a solution of copper (I) bromide (6.0g, 42 mmol) in 50% hydrobromic acid (40 ml) at 0°C. After 1 hour, the reaction was warmed to room temperature and then heated at 60°C for 3 hours. The reaction mixture was then poured onto ice and made basic with aqueous ammonia and extracted with trichloromethane. Drying (MgSO.) and evaporation in vacuo was followed by re-dissolution in tetrahydrofuran and precipitation of the product with hydrogen chloride gas. Recrystallisation (isopropanol) gave 2.1g 4- [2'-(p-bromophenyl)ethyl]piperidine hydrochloride as yellow crystals. M.pt. 118-122"C. Analysis: Calc. 51.3; H:6.3; N:4.6% Found C51.2; H:6.6; N:4.7% The free base was released by extraction from 2N sodium hydroxide solution.

(iv) Preparation of N-(p-chlorobenzyl)-4-f2' -(p-bromophenyl)- ethyl] iperidine

The free 4-(2'-(p-bromophenyl)ethyl]piperidine (l.Og, 3.7 mmol) obtained in (iii) above, p-chlorobenzyl chloride (0.6g, 3.7 mmol) and potassium carbonate (0.67g, 4.8 mmol) in ethanol (30 ml) were refluxed for 16 hours. , The solvent was then evaporated and the reaction mixture partitioned between ethyl acetate and water. Drying of the organic phase (MgSO, ) and evaporation followed by flash column chromatography on silica using 9:1 petroleum ether:ethyl acetate as eluant gave 1.2g N-(p-chlorobenzyl)-4- [2' -(p-bromophenyl)ethyl]piperidine as white crystals. M.pt. 68-69"C

Analysis: Calc. C61.2; H:5.9; N:3.6% Found C61.0; H:6.5; N:3.7% Example 6 Preparation of N-n-hexyl-4- [3'-(p-t-butylphenyl)propyl)piperidine (R¹«4-C(CH₃)_:ιphenyl; n-1; m-0; R -ⁿC_cH₁₃) (i) Preparation of 1-(p-t-butylphenyl)-3-(4' -pyridyl)- prop-2-en-1-one A mixture of 4-pyridine carboxaldehyde (16.lg, 0.15 mol), p-t-butylacetophenone (17.6g, 0.10 mol), piperidine (2g) and acetic acid (2g) was heated at 120°C for l hours. Following removal of volatiles under reduced pressure, the residue was taken up in dichloromethane and washed with 2N hydrochloric acid. Evaporation of the solvent afforded the product which was washed with water then dichloromethane and dried to give 13.Og 1-(p-t-butylphenyl)-3- (4' -ρyridyl)prop-2-en-l-one as its dihydrate hdyrochloride in the form of yellow crystals. M.pt. 233-235°C Analysis: Calc. C64.0; H:7.2; N:4.2% Found C64.4; H:6.7; N:4.2% (ϋ) Preparation of 4-f3'-(p-t-butylphenyl)propyllpiperidine The pyridine (12.2g, 36 mmol) obtained in (i) above in a mixture of ethanol (110 ml), water (20 ml) and cone, hydrochloric acid (5 ml) was hydrogenated under Parr conditions at 50°C using palladium on charcoal (10%) as catalyst until hydrogen uptake ceased. The catalyst was then filtered off and the solvent evaporated. The residue was then taken up in 30% aqueous sodium hydroxide and extracted with diethyl ether (x3). Following drying (MgSO, ) , the combined organic extracts were evaporated and the resulting product purified by flash column chromatography on silica using_.9:1 methanol:triethylamine as eluant to give 3.6g 4- [3' -(p-t-butylphenyl)propyl]piperidine as an air sensitive oil which was used directly as such in the next step.

(iii) Preparation of N-n-hexyl-4- [3'-(p-t-butylphenyl)propyl] - piperidine The piperidine (0.8g, 3.1 mmol) obtained in (ii) above, n-bromohexane (0.51g, 3.1 mmol), potassium carbonate (0.60g,

4.0 mmol) and ethanol (2.5 ml) were refluxed together for 17 hours.

After cooling and evaporation of solvent, the residue was portioned between ethyl acetate and water. Drying (MgSO.) and evaporation afforded an oil which was purified by flash column chromatography on silica using 1:4 ethyl acetate:petroleum ether as eluant to give

0.6g N-n-hexyl-4- [3'-(p-t-butylphenyl)propyl]piperidine as a pale beige oil.

Analysis: Calc. C:83.9; H:12.0; N:4.1% Found C84.0; H:12.6; N:4.4%

Examples 7 to 45

By processes similar to those described in Examples 1, 2 and 3 above, further compounds according to the invention were prepared as detailed in Table I below. In this table, the compounds are identified by reference to formula IA.

TABLE 1

(IA)

TABLE 1 (continued)

Analysis (%)

Ex. C H M.pt. No. R^J R^{^} Calc. Found Calc. Found Calc. Found (°C)

42 4-t-butylphenyl 4-chlorophenyl 78.2 76.9 8.9 8.9 3.7 3.7

43 4-methylphenyl 4-chlorophenyl 7.2(m,4H), 7.1(m,4H), 3.4(s,2H), 2.8(d br,2H), 2.5(t,2H), 2.3(s,3H), 1.9(t br, 2H) , 1.6(m,4H), 1.2(m,5H)

44 4-methylphenyl phenyl 7.3(m,5H), 7.1(m,4H), 3.5(s,2H), 2.9(d br, 2H) , 2.5(t,2H), 2.3(s,3H), 1.9(t br,2H), 1.6(m,4H), 1.2(m,5H)

45 4-methylphenyl n-CH.., 7.0(m,4H), 2.8(d br,2H), 2.5(t,2H), 2.3(s,3H), 2.2(m,2H), 1.8(t br,2H), 1.6(m,4H), 1.4(m,2H), 1.2(m,llH), 0.8(t,3H)

Example 46

The fungicidal activity of compounds of the invention was investigated by means of the following tests.

(a) Antisporulant activity against vine downy mildew (Plasmopara viticola; PVA)

The test is a direct antisporulant one using a foliar spray.

The lower surfaces of leaves of whole vine plants (cv Cabernet

Sauvignon) are inoculated by spraying with an aqueous suspension

4 containing 2.5 x 10 zoosporangia/ml 2 days prior to treatment with the test compound. The inoculated plants are kept for 24 hours in a high humidity compartment, then 24 hours at glasshouse ambient temperature and humidity. Infected leaves are sprayed on their lower surfaces with a solution of active material in 1:1 water/acetone containing 0.04% "TWEEN 20" (Trade Mark; a polyoxyethylene sorbitan ester surfactant) . Plants are treated using an automated sprayline with an atomising nozzle. The concentration of the compound is 1000 ppm, and the spray volume is 700 1/ha. After spraying, the plants are returned to normal glasshouse conditions for 96 hours and are then transferred to the high humidity compartment for 24 hours to induce sporulation, prior to assessment. Assessment is based on the percentage of the leaf area covered by sporulation compared with that on control leaves. (b) Direct protectant activity against tomato late blight (Phytophtera infestans; PIP) The test is a direct protectant foliar spray. Tomato plants with two expanded leaves (cv First in the Field) are sprayed with the test compound as described under (a). After drying, the plants are kept for 24 hours in the glasshouse at 20°C and 40% R.H. Then, the upper surfaces of the leaves are inoculated with an aqueous suspension containing 2 x 10 zoosporangia/ml. The inoculated plants are kept for 24 hours at 18°C in a high humidity cabinet and 5 days at 15^βC and 80% R.H. in a growth chamber with 14 hours light/day. The assessment is based on the percentage of diseased leaf area compared with that on control leaves. (c) Direct protectant activity against broad bean grey mould (Botrytis cinerea; BCB)

The test is a direct protectant one using a foliar spray. The upper surfaces of leaves of broad bean plants (cv The Sutton) are sprayed with the test compound at a dosage of 1000 ppm using an automated sprayline as described under (a) . 24 hours after spraying the leaves are inoculated with an aqueous suspension containing 10 conidia/ml. For 4 days after inoculation plants are kept moist in a humidity compartment at 22^βC Disease is assessed 4 days after inoculation, based on the percentage of leaf surface area covered by lesions.

(d) Activity against wheat leafspot (Leptosphaeria nodorum; LN.) The test is a direct therapeutic one, using a foliar spray.

Leaves of wheat plants (cv Norman), at the single leaf stage, are inoculated by spraying with an aqueous suspension containing 1.5 x 10 spores/ml. The inoculated plants are kept for 24 hours in a high humidity compartment prior to treatment. The plants are sprayed with a solution of the test compound at a dosage of 1000 ppm using an automated sprayline as described under (a) . After drying, the plants are kept for 6-8 days at 22 C and moderate humidity, followed by assessment. Assessment is based on the density of lesions per leaf compared with that on leaves of control plants.

(e) Activity against barley powdery mildew (Erysiphe graminis f.sp. hordei; EG)

The test is a direct therapeutic one, using a foliar spray. Leaves of barley seedlings, (cv. Golden Promise) are inoculated by dusting with mildew conidia one day prior to treatment with the test compound. The inoculated plants are kept overnight at glasshouse ambient temperature and humidity prior to treatment. The plants are sprayed with the test compound at a dosage of 1000 ppm using an automated sprayline as described under (a) . After drying, plants are returned to a compartment at 18^βC and moderate humidity for up to 7 days, followed by assessment. Assessment is based on the percentage of leaf area covered by sporulation compared with that on leaves of control plants.

(f) Activity against apple scab in-vitro (Venturia inaequalis: VII) This test measures the in-vitro activity of compounds against

V. inaequalis that causes apple scab. The test compound in acetone is added into 4 ml aliquots of half strength Potato Dextrose Broth dispensed in 25-compartment petri dishes to give final concentrations of 100 ppm. The fungal inoculum consists of mycelial fragments and spores of V. inaequalis grown on malt agar

4 and added to the broth to proide 5 x 10 propagules/ml broth.

Petri dishes are incubated at 20°C for 10 days until the assessment of mycelial growth.

(g) Activity against rice leaf blast (Pyricularia oryzae; PO) The test is a direct therapeutic one using a foliar spray.

The leaves of rice seedlings (cv Aichiaishi - about 30 seedlings per pot) are sprayed with an aqueous suspension containing 10 spores/ml 20-24 hours prior to treatment with the test compound. The inoculated plants are kept overnight in high humidity and then allowed to dry before spraying with the test compound at a dosage of 1000 ppm using an automated sprayline as described under (a) . After treatment the plants are kept in a rice compartment at 25-30 C and high humidity. Assessments are made 4-5 days after treatment and are based on the density of necrotie lesions per leaf when compared with control plants.

(h) Activity against tomato early blight (Alternaria solani; AS) This test measures the contact prophylactic activity of test compounds applied as a foliar spray. Tomato seedlings (cv Outdoor Girl) are grown to the stage at which the second true leaf is expanded. The plants are treated using an automated sprayline as described under (a) . Test compounds are applied as solutions or suspensions in a mixture of acetone and water (50:50 v/v) containing 0.04% surfactant ("TWEEN 20" - Trade Mark). One day after treatment the seedlings are inoculated by spraying the leaf upper surfaces with a suspension of Λ^ solani conidia containing 4 10 spores/ml. For 4 days after inoculation plants are kept moist in a humidity compartment at 21 C. Disease is assessed 4 days after inoculation, based on the percentage of leaf surface area covered by lesions. (i) Activity against wheat eyespot in-vitro (Pseudocercosporella herpotrichoides; PHI)

This test measures the in vitro activity of compounds against the fungus causing wheat eyespot. The test compound is dissolved or suspended in acetone and is added to molten half strength Potato Dextrose Agar to give a final concentration of lOOppm compound and

3.5% acetone. After agar has set, plates are inoculated with 6mm diameter plugs of agar/mycelium taken from a 14 day old culture of

P. herpotrichoides. Plates are incubated at 20 C for 12 days and radial growth from the inoculation plug is measured. (j ) Activity against Rhizoctonia in-vitro (Rhizoctonia solani:

RSI)

This test measures the in-vitro activity of compuonds against

R. solani that causes stem and root rots. The test compound in acetone is added into 4 ml aliquots of half strength Potato Dextrose Broth dispensed in 25-compartment petri dishes to give final concentrations of 100 ppm. The fungal inoculum consists of mycelial fragments of R. solani growth in half strength PDB in

4 shaken culture flasks and added to the broth to provide 5 x 10 fragments/ml broth. Petri dishes are incubated at 20°C for 10 days until the assessment of mycelial growth.

The extent of disease control in all the above tests is expressed as a rating compared with either an untreated control or a diluent-sprayed-control, according to the criteria: -

0 - less than 50% disease control

1 - about 50-80% disease control

2 - greater than 80% disease control The results of the tests are set out in Table II below (for compounds 5, 6 and 22-45 dose rates were 600 ppm instead of

1000 ppm in the in vivo tests, and 10 ppm instead of 100 ppm in the in vitro tests) . 03

- 29 - TABLE II

Comp . PVA PIP BCB LN EG VII PO AS PHI RSI

403

The fungicidal activity of compounds of the general formula II was investigated in the same way as described in Example 46. The results are set out in Table III below for compounds A (4-(2'-p-t- butylphenyl)ethylpiperidine) and B (4-(4'-phenyl)-n-butyl- piperidine) .

TABLE III

Comp. PVA PIP BCB LN EG VII P0 AS PHI RSI

A 2 0 B 0 0 1 0 0

Claims

C L A I M S

1. A method of combating fungi at a locus which comprises treating the locus with a compound of the general formula

or an acid-addition salt thereof, in which R represents an aryl group which may be substituted by one or more substituents,

2 R represents a hydrogen atom or an alkyl or phenyl group,

3

R represents a hydrogen atom or an alkyl or phenyl group,

4 R represents an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heterocyclyl group, m represents an integer from 0 to 3, and n represents an integer from 0 to 2.

2. A method according to claim 1 in which R represents a phenyl group optionally substituted by one or more fluorine, chlorine or bromine atoms, cyano, C , alkyl, C , haloalkyl, C- , alkoxy, C haloalkoxy, C , alkylamino, di-C , alkylamino, C alkoxycarbonyl, or phenyl groups.

3. A method according to claim 1 or claim 2 in which R 2 and R3 represent hydrogen.

4. A method according to any one of the preceding claims in which 4 R represents a C^^ alkyl, C_{2 12} alkenyl, , ₁₂ alkynyl, C. cycloalkyl, phenyl, pyridyl or thienyl group, each group being optionally substituted by one or more substituents selected from fluorine, chlorine or bromine atoms or C , alkyl, C , haloalkyl, C alkoxy, C . haloalkoxy, C. , alkylamino, di-C alkylamino,

C alkylcarbonyl, C , alkoxycarbonyl, or phenyl groups.

5. A method according to any one of the preceding claims in which m represents 0, 1 or 2.

6. A compound of the general formula I as defined in claim 1 with the provisos that:- (i) when m is 0, n is 0 and R represents a 4-fluorophenyl group,

4 then R does not represent a n-pentyl group;

(ii) when m is 0, n is 0 and R represents a phenyl group, then R does not represent a 2-(dimethylamino)ethyl or 2,3-dihydroxy-

3,7,11-trimethyldodec-1-yl group; (iii) when m is 0, n is 0 and R represents a 2-methylphenyl

4 group, then R does not represent a methyl group; and

(iv) when m is 0, n is 1 and R represents a phenyl group, then R does not represent a methyl, 2-chloroethyl, 2-hydroxyethyl,

4-hydroxybutyl or n-pentyl group.

7. . A process for the preparation of a compound of the general formula I as defined in claim 6 or an acid addition salt thereof which comprises reacting a compound of the general formula

in which R and n are as defined in claim 6, with a compound of the general formula

2 3 4 X—(CR R ) —R III m

2 3 4 in which m, R , R and R are as defined in claim 6 and X represents a leaving group, and, if desired, reacting the compound of the general formula I so obtained with a suitable acid to form an acid-addition salt thereof.

8. A fungicidal composition which comprises a carrier and, as active ingredient, a compound of the general formula I or an acid addition salt thereof as defined in claim 6.

9. The use as a fungicide of a compound of the general formula I or an acid addition salt thereof as defined in any of claims 1 to 6 or a composition as defined in claim 8.

10. The use according to claim 9 against fungicidal diseases in cereals.

11. A compound of the general formula

II

or an acid addition salt thereof, in which R and n are as defined in any one of claims 1, 2 and 6.

12. A fungicidal composition comprising a compound as claimed in claim 11, together with at least one carrier.

13. A method of combating fungi at a locus which comprises treating the locus with a compound of the general formula II or an acid addition salt thereof as defined in claim 11.

14. The use as a fungicide of a compound of the general formula II or an acid addition salt thereof as defined in claim 11 or a composition as defined in claim 12.