WO1992016518A1

WO1992016518A1 - Aminoethyl ketals, their preparation and intermediate products therefor, and their use as fungicides

Info

Publication number: WO1992016518A1
Application number: PCT/DK1992/000066
Authority: WO
Inventors: Anita Wengel; Axel Svendsen; Ib Winckelmann; Niels Jacobsen; Hans Kolind-Andersen; Per Dausell Klemmensen
Original assignee: Cheminova Agro A/S
Priority date: 1991-03-22
Filing date: 1992-03-04
Publication date: 1992-10-01
Also published as: IE920753A1; ZA921743B; DK51691D0; PT100273A; AU1532592A

Abstract

Aminoethyl ketals of formula (I), wherein R1 is C¿1¿-C¿10?alkyl, unsubstituted or alkylsubstituted cycloalkyl having up to 6 ring carbon atoms or cycloalkylalkyl having up to 10 carbon atoms in all, R?2 and R3¿ each independently represents hydrogen, C¿1?-C10alkyl, unsubstituted or alkylsubstituted cycloalkyl, alkenyl having up to 10 carbon atoms, alkynyl or unsubstituted or alkylsubstituted cycloalkylalkyl, or R?2 and R3¿ when taken together with the nitrogen atom to which they are attached form a substituted or unsubstituted heterocyclic ring which may optionally contain one or more additional hetero atoms selected from O and N, and the preparation of these compounds and intermediate products therefor are described. The compounds (I) have fungicidal, particularly plant-fungicidal activity.

Description

A inoethyl ketals, their preparation and intermediate products therefor, and their use as fungicides.

The present invention relates to novel amino¬ ethyl ketals, a process for their preparation and novel intermediate products therefor. Moreover, the invention relates to the use of the novel aminoethyl ketals as fungicides, particularly plant-fungicides.

From European published specification No. EP 0 349 247 A2 (corresponding to PCT published speci¬ fication No. WO 90/00169, confer the application pro¬ ceeded with, Danish patent application No. 3058/90) there are known fungicidally active amino ketals of the general formula

wherein X and Y each independently represents O or

-0CH₂-,

(R¹)_n represents up to four substituents which are the same or different and selected from straight or branched chain alkyl having up to 10 carbon atoms, cycloalkyl having up to 6 carbon atoms, aryl, aryloxy, alkoxy, cycloalkoxy, arylalkyl and alkylthio, where two adjacent R¹-substituents may also together form a saturated or unsaturated ring, and n is 1, 2, 3 or 4, and m is 0, 1, 2, 3 or 4, and R² and R³ each independently represents hydrogen, straight or branched chain alkyl having up to 10 carbon atoms, unsubstituted or alkylsubstituted cycloalkyl, alkenyl,aikynyl or unsubstituted or alkylsubstituted arylalkyl, or R² and R³ when taken together with the nitrogen atom to which they are attached form a saturated or unsaturat¬ ed, substituted or unsubstituted heterocyclic ring which may optionally be aryl-fused or cycloalkyl-fused and which may optionally contain one or more additional hetero atoms selected from 0 and N, with the proviso that if X and Y are both 0, m is 1, and -NR²R³ is other than an unsaturated, substituted or unsubstituted heterocyclic ring which may optionally be aryl-fused or cycloalkyl-fused and which may op- tionally contain one or more additional hetero atoms selected from O and N, then

cannot be a sole substituent (n=l) in the 4-position in the cyclohexane

I 3 ring and of the formula R-C-, wherein R represents CH₃ hydrogen, alkyl or optionally substituted phenyl.

The actually known compounds falling under the above general formula are shown by formulae in Table 1 on pages 9-39 in EP 0 349 247 A2 (pages 15-45 in WO 90/00169).

Specifically, mention should be made of

2-(2-N,N-dipropylaminoethyl)-8-(1,1-dimethylpropyl)-

1,4-dioxaspiro[4.5]decane,

2-(2-piperidinoethyl)-8-(1,1-dimethylpropyl)-1,4- dioxaspiro[4.5]decane and

2-(2-(2,6-dimethylmorpholino)ethyl)-8-(1,1-dimethyl- ethyl)-1,4-dioxaspiro[4.5]decane.

However, the fungicidal activity of sa,id known compounds especially at low amounts of application, is not quite satisfactory on all fields of application.

According to this invention there are now provided amino ketals having a generally superior fungicidal activity, viz. novel aminoethyl ketals of the general formula I

wherein R¹ represents a substituent selected from straight or branched chain alkyl having up to 10 carbon atoms, unsubstituted or alkylsubstituted cycloalkyl having up to 6 ring carbon atoms and cycloalkylalkyl having up to 10 carbon atoms in all,

R² and R³ each independently represents hydrogen, straight or branched chain alkyl having up to 10 carbon atoms, unsubstituted or alkylsubstituted cycloalkyl, alkenyl having up to 10 carbon atoms, aikynyl or un¬ substituted or alkylsubstituted cycloalkylalkyl, or R² and R³ when taken together with the nitrogen atom to which they are attached form a substituted or un- substituted heterocyclic ring which may optionally contain one or more additional hetero atoms selected from 0 and N, with the exception of the compounds falling under formula I which occur in Table 1 on pages 9-39 of EP 0 349 247 A2.

The symbols R¹-R³ in the above formula I have preferably, or by way of example, the following mean¬ ings: R¹: alkyl is preferably alkyl having 4-10 carbon atoms, more preferably branched chain alkyl having 4-8 carbon atoms, substituted cycloalkyl is preferably 1-methylcyclohexyl, cycloalkylalkyl is preferably 1-methyl- 1-cyclohexylethyl,

R² and R³: straight and branched chain alkyl is preferably alkyl having up to 6 carbon atoms and more preferably up to 4 carbon atoms, cycloalkyl is preferably cyclopropyl or cyclopentyl, cycloalkylalkyl is preferably cyclopro- pylmethyl, alkenyl is preferably allyl, methallyl or 3-butenyl, aikynyl is preferably propargyl, and the optionally substituted heterocyclic ring is preferably 2-methylmorpholino, 2-ethylmorpholino or 2-methyl~6-ethyl- morpholino (cis/trans or cis or trans). Compounds of formula I can exist as geometrical and/or optical isomers or isomer mixtures of varying composition. The present invention relates to both the pure isomers and isomer mixtures.

Quite particularly compounds are preferred in which R² and R³ do not simultaneously have the same meaning.

Furthermore, it has been found that the novel aminoethyl ketals of the general formula I, wherein the substituents R¹, R² and R³ have the above defined meanings, are obtainable by reacting a ketal of the general formula II

wherein R¹ has the above defined meaning, and wherein Z represents an exchangeable electron-attracting group as, e.g., a halogen atom or an alkanesulphonyloxy group or an arylsulphonyloxy group, with an amine of the general formula III

wherein R² and R³ have the above defined meanings, optionally in the presence of a solvent and optionally in the presence of a catalyst, and optionally in the presence of an acid-binding agent in addition to a possible excess of the amine III. Optionally, the reaction between the ketals II and the amines III under the above-mentioned conditions can furthermore take place in an autoclave at a pressure above atmospheric pressure.

Suitable solvents are, e.g., methyl-t-butyl ether, tetrahydrofuran, di ethylformamide, acetoni- trile, toluene, xylene, 1,2-dichloroethane or dimethyl- sulphoxide. Suitable acid-binding agents are, e.g., sodium carbonate, potassium carbonate, triethylamine, pyridine or diazabicyclooctane (DABCO) .

The reaction temperature at the reaction between the ketals II and the amines III can vary within a wide range. Usually, there is operated in a temperature

0 0 range of between 20 C and 200 C, preferably between 100°C and 180°C .

The ketals of formula II, e.g. when it is a question of methanesulphonates (Z = OS0₂CH₃) , are obtainable by reacting a ketal alcohol of formula IV

wherein R¹ has the above defined meaning, with ethane- sulphonyl chloride of formula V

CH₃S0₂C1 V

in a manner known per se in the presence of a solvent as for example methyl-t-butyl ether, toluene, methyl- ene chloride or acetonitrile, and in the presence of an acid-binding agent as for example potassium carbonate, triethylamine or pyridine, at temperatures of between 0 C and 100 C.

The ketal alcohols of formula IV can be prepared in a generally known manner by reacting a ketone of formula VI

wherein R¹ has the above defined meaning, with 1,2,4- butanetriol of formula VII

in the presence of an aprotic organic solvent such as toluene or 1,2-dichloroethane, and in the presence of an acidic catalyst such as p-toluenesulphonic acid at the boiling point of the solvent concerned while simultaneously azeotropically distilling off the water formed during the ketalization reaction.

Furthermore, the ketals of formula II, when it is a question of chloroketals (Z = Cl) are obtainable by reacting a ketone of formula VI with l,2-epoxy-4- chlorobutane which is known from Liebigs Ann. Chem.

596, 141-2 (1955) and has the formula VIII

in a manner known per se in the presence of a solvent and in the presence of a catalyst (confer what is stated in React. Kinet. Catal. Lett. 1981, 17(3-4), 281-6) .

Suitable solvents are, e.g., aliphatic or aro¬ matic hydrocarbons such as hexane, cyclohexane or toluene, chlorinated hydrocarbons such as methylene chloride, 1,2-dichloroethane or chlorobenzene, esters such as ethyl acetate, nitriles such as acetonitrile, or compounds containing the atomic grouping S0₂ such as sulphur dioxide itself, di etyl sulfone or sulfolane.

Suitable catalysts can be metal halides such as FeCl₃, TiCl₄, AICI3, ZnCl₂, NiBr₂, PdBr₂, AlF₃, SbF₃, Cul and the like, or halides of boron and silicon such as BF₃, BBr₃ and SiCl₄, or an acidic silicate-catalyst such as bentonite, montmorillonite and the like, which can optionally be activated by treatment with acid and/ or ion exchange and/or drying. Two examples of the catalysts used are BF₃ added in the form of its complex with diethyl ether and aluminium-activated bentonite.

The catalyst can be used in an amount of from 0.1 to

50% by weight, preferably from 1 to 10% by weight. During the reaction the temperature of the

0 reaction mixture is kept between about -30 C and about +200 C, preferably between about +20 C and about +100°C.

The reactants can be present in the solvent in a concentration of between 10 and 100% by weight, based on the solvent.

The ketals of formula II wherein Z = 0S0₂CH₃, the ketals of formula II wherein Z = Cl and the ketal alcohols of formula IV are novel compounds and are also the object of the invention in the form of an inter- mediate product and a starting material as stated in claims 4 and 5, respectively.

It has been found that the novel aminoethyl ketals of formula I have fungicidal properties. Sur¬ prisingly, the aminoethyl ketals of the general formula I according to the invention exhibit a fungicidal activity superior to that of the amino ketals known from the state of the art, for example 2-(2-N,N-dipropylaminoethyl)-8-(1,1-dimethylpropyl)- 1,4-dioxaspiro[4.5]decane, 2-(2-piperidinoethyl)-8-(1,1-dimethylpropyl)-1,4-dioxa¬ spiro[4.5]decane and

2-(2-(2,6-dimethylmorpholino)ethyl)-8-(1,1-dimethyl- ethyl)-1,4-dioxaspiro[4.5]decane, which chemically and in respect of activity are close- ly related compounds.

The active substances of the invention can be used in practice for combating phytopathogenic fungi as for example Plasmodiophoromycetes, Chytridiomycetes,

Zygomycetes, Ascomycetes, Basidiomycetes and Deutero- mycetes.

The active substances of the invention can be used, e.g., for combating the plant diseases Puccinia recondita, Puccinia striiformis and other rust diseases on wheat, Puccinia hordei, Puccinia striiformis and other rust diseases on barley and rust on other host plants as for example coffee, apples, vegetables and ornamental plants.

Erysiphe graminis (mildew) on barley and wheat and other true mildew species on various host plants such as Sphaerotheca fuliqinea on cucumber, Podosphaera leucotricha on apples and Uncinula necator on vines. Helminthosporlum spp., e.g. Pyrenophora teres (net blotch) on barley.

Rhynchosporium spp. and Pseudocercosporella herpotri- choldes on cereals. Cercospora arachidicola on peanuts and other Cercospo¬ ra species on for example sugar beet, banana and soya bean.

Botrytls cinerea (grey mold) on tomato, strawberry, vine and other host plants. Venturia inaequalis (scab) on apples. Pyrlcularia oryzae on rice.

The active substances are active in vitro against a broad spectrum of fungi.

The active substances are active as seed dressing agents against Fusarium spp., Septoria spp., Tllletia sp . , Ustilaqo spp. , Helminthosporium spp. and Pseudocercosporella herpotrichoides on cereals, Rhizoctonia solani on cotton and Cortlcium sasakii on rice. Besides an excellent curative activity the active substances of the invention also show extremely good protective properties as well as systemic activi¬ ty.

In addition to this some of the compounds are sufficiently volatile to be active in the gaseous phase against fungi on plants.

The compounds 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 are also useful for the treatment of human fungal infections as for example candidiasis and dermatophyte infections. In accordance with the above the invention also relates to a fungicidal composition, particularly a plant-fungicidal composition, and more particularly a cereal-fungicidal composition for combating mildew, rust and other significant foliage diseases, which composition is characterised by containing as an active component at least one compound selected from the ami¬ noethyl ketals of the above formula I.

Moreover, the invention relates to the use of an aminoethyl ketal of the above formula I for combating fungi, particularly phytopathogenic fungi, and more particularly mildew, rust and other significant foliage diseases on cereals.

Furthermore, the invention relates to a method of combating fungi, particularly phytopathogenic fungi, and more particularly mildew, rust and other signifi¬ cant foliage diaseses on cereals, which method is characterised by allowing an aminoethyl ketal of the above formula I to affect the fungi concerned and/or their biotope.

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, or they can be applied to bushes and trees, to seeds or to other media 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 formula¬ tion, 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 soil generally, to paddy water or to hydroponic culture systems. The compounds of the invention may also be injected into plants or trees and they may also be sprayed onto vegetation using elect odynamic spraying techniques. Furthermore, the invention relates to a process of preparing a fungicidal composition, particularly a plant-fungicidal composition, and more particularly a cereal-fungicidal composition for combating mildew, rust and other significant foliage diseases, which process is characterised by mixing an aminoethyl ketal of the above formula I with one or more agents select¬ ed from extending agents, surface active agents and other conventional auxiliary agents. The compositions may be in the form of dusting 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 im¬ pregnating 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 dimethyl- formamide) .

The compositions may also be in the form of dispersible powders or granules comprising a wetting agent to facilitate the dispersion in liquids of the powder or granules 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, dis¬ persing or emulsifying agents and then adding the mixture to water which may also contain wetting, dis¬ persing or emulsifying agents. Suitable organic sol¬ vents are ethylene dichloride, isopropyl alcohol, propylene glycol, diacetone alcohol, toluene, kerosene, methylnaphthalene, the xylenes, trichloroethylene, furfuryl alcohol, tetrahydrofurfuryl alcohol, and glycol ethers (e.g. 2-ethoxyethanol and 2-butoxy- ethanol) .

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, e.g. fluorotrichloromethane or dichloro- difluoromethane.

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 fer¬ tilisers (e.g. nitrogen-, potassium- or phosphorus-con¬ taining 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.

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, e.g. wetting agents, dispersing agents, emulsifying agents or suspending agents, 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 aromatic compounds (for example sodium dodecylbenzene- sulphonate, sodium, calcium or ammonium lignosul- phonate, butylnaphthalene sulphonate, and a mixture of sodium diisopropyl- and triisopropyl-naphthalene sul- phonates) .

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 polyvinylpyrro- lidone and sodium carboxy ethylcellulose) , and the vegetable gums (for example gum acacia and gum traga- canth) . The 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(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 homo¬ geneous 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 (e.g. alkyl 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 ingredients in the polar solvents often used in the concentrates. The concentrates suitably contain also a high pro¬ portion of surfactants so that sufficiently stable emulsions in water can be obtained. After dilution to form aqueos preparations, such preparations may contain varying amounts of the active ingredients depending upon the intended purpose, but an aqueous preparation containing 0.0005% or 0.01% to 10% by weight of active ingredient may be used. The compositions of this invention can comprise also other compounds having biological activity, e.g. 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 (e.g. wheat) such as Septoria, Gibberella and Helminthosporium spp., seed and soil borne diseases and downy and powdery mildews on vines and powdery mildew and scab on apples etc. These mix¬ tures of fungicides can have a broader spectrum of activity than the compound of general formula I alone. Furthermore, 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, thiabend- azole, fuberidazol, etridazol, dichlofluanid, cymox- anil, oxadixyl, ofurace, metalaxyl, furalaxyl, benalax- yl, fosetyl-aluminium, fenarimol, iprodion, procymi- dion, vinclozolin, penconazol, myclobutanil, R0151297, S3308, pyrazophos, ethirimol, ditalimfos, tridemorph, triforin, nuarimol, triazbutyl, guazatin, triacetate salt of 1,1'-iminodi(octamethylene)-diguanidine, pro- piconazol, prochloraz, flutriafol, hexaconazol, i.e. the compound l-(l,2,4-triazol-l-yl)-2-(2,4-dichloro- phenyl)hexan-2-ol, DPX H6573 (l-( (bis-4-fluorophenyl)- methyl-silyl)methyl-lH-l,2,4-triazol, triadimefon, triadimenol, diclobutrazol, fenpropimorph, pyrifenox, (2RS,3RS)-2-(4-chlorophenyl)-3-cyclopropyl-l-(1H-1,2,4- triazol-1-yl)butan-2-ol, (RS)-1-(4-chlorophenyl-4,4-di- methyl-3-(lH-l,2,4-triazol-l-ylmethyl)-pentan-3-ol, 4- chloro-N-(cyano(ethoxy)methyl)benzamide, fenpropidin, chlorozolinate, diniconazol, imizalil, fenfuram, carb- oxin, oxycarboxin, methfuroxam, dodemorph, BAS 454, blasticidin S, kasugamycin, edifenphos, kitazin P, cycloheximide, phthalide, probenazol, isoprothiolan, tricyclazol, pyroquilon, chlorbenzthiazon, neoasozin, polyoxin D, valida ycin A, mepronil, flutolanil, pency- curon, diclomezin, phenazineoxide, nickel dimethyldi- thiocarbamate, techlofthalam, bitertanol, bupirimat, etaconazol, streptomycin, cypofuram, biloxazol, quino- methionate, dimethirimol, l-(2-cyano-2-methoxyimino- acetyl)-3-ethyl urea, fenapanil, tolclofosmethyl, pyroxyfur, polyram, maneb, mancozeb, captafol, chloro- thalonil, anilazin, thiram, captan, folpet, zineb, propineb, sulphur, dinocap, binapacryl, nitrothaliso- propyl, dodine, dit ianon, fentin hydroxide, fentin acetate, tecnazene, quintozen, dichloran, copper-con¬ taining compounds such as copper oxychloride, copper sulphate and Bordeaux mixture as well as organic mercury compounds.

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

Suitable insecticides that can 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, chlor- pyrifos, isoxathion, propaphos, monocrotophos, bu- profezin, ethoproxyfen and cycloprothrin. Plant growth regulating compounds for use in compositions of the invention 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 compositions of the inven¬ tion are the gibberellins (e.g. GA₃, GA₄ or GA₇), the auxins (e.g. 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. chlor- fluorecol), maleic hydrazide, glyphosate, glyphosine, long chain fatty alcohols and acids, dikegulac, paclo- butrazol, fluorprimidol, fluoridamid, mefluidide, substituted quaternary ammonium and phosphonium com¬ pounds (e.g. chlormequat, chlorphonium or mepiquat- chloride), ethephon, carbetamide, methyl-3,6-dichloro- anisate, daminozide, asulam, abscisic acid, isopyrimol, 1-(4-chlorophenyl)-4,6-dimethyl-2-oxo-l,2-dihydropyri- dine-3-carboxylic acid, hydroxybenzonitriles (e.g. bromoxynil), difenzoquat, benzoylprop-ethyl 3,6-di- chloropicolinic acid, fenpentezol, inabenfid, tria- penthenol, and tecnazene.

The invention is further illustrated by means of the following Preparations, Preparation Examples and Application Examples.

Preparation 1

Preparation of the intermediate product 2-(2-methane- sulphonyloxyethyl)-8-(1,1 ,2-trimethylpropyl)-1,4-dioxa- spiro[4.5]decane

A solution of 2-(2-hydroethyl)-8-(l,l,2-trime- thylpropyl)-l,4-dioxaspiro[4.5]decane (19.4 g, 0.08 mol) and triethylamine (10.1 g, 0.1 mol) in methylene chloride (80 ml) is cooled in an ice bath, while a solution of methanesulphonyl chloride (10.8 g, 0.088 mol) in methylene chloride (20 ml) is added dropwise at such a rate that the reaction temperature does not

0 exceed 15 C. After completion of the dropwise addition the reaction mixture is stirred at room temperature for an hour and then the solvent is evaporated in vacuo. The residue from evaporation is redissolved in methyl- t-butyl ether (150 ml) and extracted with water (2 x 100 ml). The organic phase is separated, dried over sodium sulphate and evaporated in vacuo to obtain a viscous oil of n_D 1.4786. The product thus obtained is used without further purification for further reaction.

Preparation 2

Preparation of the starting material 2-(2-hydroxy- ethyl)-8-(1,1-dimethylethyl)-1,4-dioxaspiro[4.5]decane

A mixture of 4-(1,1-dimethylethyl)-cyclohexanone (15.4 g, 0.1 mol), l,2,4-butanetriol (11.7 g, 0.11 mol) and p-toluenesulphonic acid (200 mg) , dissolved in toluene (150 ml), is heated under reflux and simul¬ taneous removal of the separated water in a water-sepa- rator. When the calculated amount of water has been collected, the reaction mixture is cooled to room temperature and triethylamine -(l ml) is added to neu¬ tralize the acidic catalyst. Shaking with water (100 ml) is performed and the organic phase is separated, dried over sodium sulphate and evaporated in vacuo. The resulting oil is purified by distillation. Yield 19.4 g (80%) of a colourless oil of b.p. 130-140 C/0.3 mm Hg; n^ 1.4752.

In a similar manner the following ketal alcohols are prepared

Preparation 3

Preparation of the intermediate product 2-(2-chloro- ethyl)-8-(1,1-dimethylethyl)-1,4-dioxaspiro[4.5]decane

A mixture of 4-(l,l-dimethylethyl)cyclohexanone (15.42 g, 0.1 mol) and 4 g of aluminium-activated bentonite in toluene (200 ml) is heated while stirring o to 60 C, and then l,2-epoxy-4-chlorobutane (13.90 g, 0.13 mol) is added dropwise during 30 minutes. The

0 reaction mixture is then allowed to stand at 60 C for a further 30 minutes. Thereafter the reaction mixture is cooled, the catalyst filtered off and the filtrate evaporated in vacuo. The resulting oil is purified by distillation. Yield 18.5 g (71%) of a viscous oil. B.p. 89-91°C/0.2 mm Hg. nξ⁶: 1.4739.

Preparation 4

Preparation of the intermediate product 2-(2-chloro- ethyl)-8-(1,1-dimethylpropyl)-1,4-dioxaspiro[4.5]- decane

A mixture of 4-(l,l-dimethylpropyl)cyclohexanone (16.83 g, 0.1 mol) and 2 g of boron trifluoride ether- ate in methylene chloride (200 ml) is heated while stirring to reflux, and then l,2-epoxy-4-chlorobutane (13.90 g, 0.13 mol) is added dropwise during 30 min¬ utes. The reaction mixture is then allowed to stand under reflux for a further 30 minutes. Thereafter the reaction mixture is cooled and thoroughly washed with 50 ml of concentrated aqueous ammonia, dried over sodium sulphate and evaporated in vacuo. The resulting oil is purified by distillation. Yield 18.4 g (67%) of

° 26 a viscous oil. B.p. 96-98 C/0.1 mm Hg. n_D: 1.4790.

In the above manner the following chloroketals are prepared

Preparation Example 1

Preparation of 2-(2-(N-allyl-N-propyl)aminoethyl)-8-

1,1-dimethylethyl)-1,4-dioxaspiro[4.5]decane, compound No. 1105

In an autoclave with glass liner a mixture of 2-(2-me hanesulphonyloxyethyl)-8-(1,1-dimethylethyl)- l,4-dioxaspiro[4.5]decane (3.20 g, 0.01 mol) and N-allyl-N-propylamine (2.97 g, 0.03 mol) is placed. The autoclave is heated to 160 C and kept at said temperature for 2 hours. After cooling to room tem¬ perature the reaction mixture is poured into 3N sodium hydroxide (15 ml) and extracted with 2 x 50 ml of petroleum ether (b.p. 40-60°C). The combined organic phases are dried over sodium sulphate and evaporated in vacuo. The resulting oil is purified by kugelrohr distillation. Yield 2.26 g (70%) of a viscous oil of

⁰ 26 b.p. 235 C/10 mm Hg; n_D: 1.4717.

Preparation Example 2

Preparation of 2-(2-(2-methylmorpholino)ethyl)-8- (1,1,2-trimethylpropyl)-1,4-dioxaspiro[4.5]decane, compound No. 1210 .

A mixture of 2-(2-methanesulphonyloxyethyl)-8- 1,1,2-trimethylpropyl)-1,4-dioxaspiro[4.5]decane- (3.13 g, 0,009 mol), 2-methylmorpholine (1.11 g, 0.011 mol), sodium iodide (0.2 g) and potassium carbonate (2.5 g) in dimethylformamide (15 ml) is heated under reflux for 2 hours. The reaction mixture is cooled and poured into water and then extracted with ether (100 ml). The ether phase is separated, dried over sodium sulphate and evaporated in vacuo. The resulting oil is purified by kugelrohr distillation. Yield 2.13 g (67%) of a vis- o 26 cous oil of boiling point 170 C/0.07 mm Hg; n_D:

1.4850.

Preparation Example 3

Preparation of 2-(2-N,N-diethylaminoethyl)-8-(1,1-di¬ methylpropyl)-l,4-dioxaspiro[4.5]decane, compound No. 1034

In an autoclave with glass liner a mixture of 2-(2-chloroethyl)-8-(1,1-dimethylpropyl)-l,4-dioxa¬ spiro[4.5]decane (2.75 g, 0.01 mol) and diethylamine (1.35 g, 0.03 mol) is placed. Otherwise, reaction and workup are carried out as stated in Preparation Example of a viscous oil of b.p. 175 C/

The aminoethyl ketals of formula I according to the invention are exemplified by specific examples of compounds as stated in the following Table 1 wherein the term Refractive Index (26C) is identical to Refrac- tive Index n_D.

Table 1 No.

1001 Refractive Index (26 C)

1.4665

No.

1002

No.

1003 Refractive Index (26 C)

1.4700

No.

1006

No.

1007 Refractive Index (26 C)

1.4682

No.

1008 Refractive Index (26 C)

1.4702 No.

1009 Refractive Index (26 C)

1.4698

No.

1013 Refractive Index (26 C)

1.4699

No.

1014 Refractive Index (26 C)

1.4690

Refractive Index (26 C)

1.4730

No.

1018 Refractive Index (26 C)

1.4672

No.

1019

No.

1020 Refractive Index (26 C)

1.4710

No.

1022 Refractive Index ⁽26 C)

1.4635

No.

1023 Refractive Index (26 C)

1.4674

No.

1024 Refractive Index (26 C)

1.4671 No.

NO.

1028 Refractive Index (26 C)

1.4808

No.

1029 Index (26 C)

No.

Refractive Index (26 C)

1.4831

Refractive Index (26 C)

1.4878 No.

1033 Refractive Index (26 C)

1.4660

No.

1034 Refractive Index (26 C)

1.4702

No.

1035 Refractive Index (26 C)

1.4700

No.

1036 Refractive Index (26 C)

1.4700

No.

Refractive Index (26 C)

1.4909

Refractive Index (26 C)

1.4867 No.

Refractive Index (26 C)

1.4661

No.

1042 Refractive Index (26 C)

1.4705

No.

1043 Refractive Index (26 C)

1.4695

No.

1044 Refractive Index (26 C)

1.4715

No.

1048 Refractive Index (26 C)

1.4671 No.

1049

No.

1050 Refractive Index (26 C)

1.4741

No.

1051 Refractive Index (26 C)

1.4700

No.

1053

No.

1054 Refractive Index (26 C)

1.4701

No.

1056 Refractive Index (26 C)

1.4700

No.

1059 Refractive Index (26 C)

1.4658

No.

1060 Refractive Index (26 C)

1.4687

No.

1061 Refractive Index (26 C)

1.4692

No.

1062 Refractive Index (26 C)

1.4752

No.

1064 Refractive Index ⁽26 C)

1.4752 No.

1065 Refractive Index (26 C)

1.4849

No.

1067 Refractive Index (26 C)

1.4671

No.

1068 Refractive Index (26 C)

1.4702

No.

1069 Refractive Index (26 C)

1.4702

No.

1070 Refractive Index (26 C)

1.4705

Refractive Index (26 C)

1.4857

1080 Refractive Index (26 C)

1.4776 No.

1081 Refractive Index (26 C)

1.4730

No.

1082 Refractive Index (26 C)

1.4769

No.

1085 Refractive Index (26 C)

1.4805

No.

1086 Refractive Index (26 C)

1.4837

No.

1087 Refractive Index (26 C)

1.4882

No.

1088 . Refractive Index (26 C)

1.4820

No.

1092 Refractive Index (26 C)

1.4730

No.

1093 Refractive Index (26 C)

1.4763

No.

1094 Refractive Index (26 C)

1.4756

No.

Refractive Index (26 C)

1.4751

Refractive Index (26 C)

1.4792

No.

Refractive Index (26 C)

1.4729

No.

1099 Index (26 C)

No.

1100 Refractive Index (26 C)

1.4754

No.

Refractive Index (26 C)

1.4921 No.

1105 Refractive Index (26 C)

1.4717

No.

1106 Refractive Index (26 C)

1.4750

No.

1107 Refractive Index (26 C)

1.4762

No.

1108 Refractive Index (26 C)

1.4744

No.

1112 Refractive Index (26 C)

1.4710 No.

1113 Refractive Index (26 C)

1.4746

No.

Refractive Index (26 C)

1.4806

No.

1115 Refractive Index (26 C)

1.4740

No.

1119 Refractive Index (26 C)

1.4718

No.

1120 Refractive Index (26 C)

1.4764 No.

Refractive Index (26 C)

1.4752

No.

Refractive Index (26 C)

1.4818

Refractive Index (26 C)

1.4850

No.

1139 Refractive Index (26 C)

1.4812

No.

1140 Refractive Index (26 C)

1.4806

No.

1141 Refractive Index (26 C)

1.4865

No.

1142 Refractive Index (26 C)

1.4892

No.

1143 Refractive Index (26 C)

1.4829

No.

1144 Refractive Index (26 C)

1.4878

Refractive Index (26 C)

1.4810

No.

1155 Refractive Index (26 C)

1.4802

No.

1156

No.

1157 Refractive Index (26 C)

1.4896

No.

Refractive Index (26 C)

1.4795

Refractive Index (26 C)

1.4829

No.

1163

No.

1164 Refractive Index (26 C)

1.4762

No.

Refractive Index (26 C)

1.4927 No.

1169

No.

1170 Refractive Index (26 C)

1.4753

No.

1171 Refractive Index (26 C)

1.4754

No.

1172 Refractive Index (26 C)

1.4748

Refractive Index (26 C)

1.4721

No.

1183 Refractive Index (26 C)

1.4849

No.

1184 Refractive Index (26 C)

1.4842 No.

Refractive Index (26 C)

1.4838

No.

1186 Refractive Index (26 C)

1.4851

No.

1188 Refractive Index (26 C)

1.4728

No.

1189 Refractive Index (26 C)

1.4760

No.

1190 Refractive Index (26 C)

1.4761

No.

1192 Refractive Index (26 C)

1.4718 No.

1193 Refractive Index (26 C)

1.4750

No.

1194 Refractive Index (26 C)

1.4746

No.

1196 Refractive Index (26 C)

1.4770

No.

Refractive Index (26 C)

1.4782

No.

Refractive Index (26 C)

1.4788

Refractive Index (26 C)

1.4832

No.

1203 Refractive Index (26 C)

1.4690

No.

1204 Refractive Index (26 C)

1.4730

No.

1205 Refractive Index (26 C)

1.4720

No.

1206 Refractive Index (26 C)

1.4790

No.

1207 Refractive Index (26 C)

1.4822

No.

1208 Refractive Index ⁽26 C)

1.4821 No.

1209 Refractive Index (26 C)

1.4800

No.

1211 Refractive Index (26 C)

1.4802

No.

1212 Refractive Index (26 C)

1.4820

No.

1213 Refractive Index (26 C)

1.4812

No.

1214 Refractive Index (26 C)

1.4802

Refractive Index (26 C)

1.4838

Refractive Index (26 C)

1.4710

APPLICATION EXAMPLES

In the following Application Examples the com¬ pounds mentioned below and known from EP 0 349 247 A2 are used as compounds of comparison.

2-(2-N,N-dipropylaminoethyl)-8-(1,1-dimethylpropyl)- 1,4-dioxaspiro[4.5]decane

and 2-(2-piperidinoethyl)-8-(1,1-dimethylpropyl)-1, - dioxaspiro[4.5]decane

and 2-(2-(2,6-dimethylmorpholino)ethyl)-8-(1,1,-dime- thylethyl)-1,4-dioxaspiro[4.5]decane

Application Example 1

Erysiphe graminis hordei (Mildew on barley). Curative spraying of young barley plants.

Solvent : 10% acetone in water. Emulsifier: Triton X-155, 100 ppm.

To prepare an appropriate composition of active substance the active substance is dissolved in the specified solvent with emulsifier to the concentration desired. Further dilution is carried out by a solution containing 10% acetone in water and 100 ppm Triton X-155. To test for curative activity young barley plants are sprayed to leaf wetness with the composition of active substance 2 days after the plants have been inoculated with mildew conidia by the brush method. After inoculation and until spraying the plants are

0 left at 18 C and 100% RH, and after spraying they are left in a growth chamber at 18 C and 70-80% RH.

7 Days after inoculation the activity of the substance is evaluated. I clear superiority in activi¬ ty in relation to the state of the art is shown by the compounds according to the Examples Nos. 1002, 1003, 1004, 1024, 1026, 1032, 1038, 1083, 1084, 1092, 1094, 1102, 1103, 1106, 1130, 1136, 1148, 1150, 1152, 1164, 1170, 1177, 1180, 1200, 1206, 1207, 1210, 1221.

Application Example 2

Puccinia recondita test (wheat, protective spray).

5 Solvent : 10% acetone in water. Emulsifier: Triton X-155, 100 ppm.

To prepare an appropriate composition of active substance the active substance is dissolved in the

10 specified solvent with emulsifier to the concentration desired. Further dilution is carried out by a solution containing 10% acetone in water and 100 ppm Triton X-155.

To test for protective activity young wheat

15 plants are sprayed to leaf wetness with the composition of active substance. After drying the plants are inocu¬ lated with brown rust spores in an aqueous slurry which

0 is sprayed on. The plants are left for 48 hours at 18 C and 100% RH, whereafter they are transferred to a

20 growth chamber at the same temperature and 70-80 RH.

10 Days after inoculation the activity of the substances is evaluated. A clear superiority in acti¬ vity in relation to the state of the art is shown by the compounds according to the Examples Nos. 1006,

25 1008, 1009, 1014, 1019, 1021, 1026, 1028, 1032, 1043, 1045, 1059, 1065, 1071, 1080, 1081, 1082, 1084, 1086, 1092, 1094, 1096, 1100, 1101, 1102, 1104, 1107, 1109, 1112 1121, 1122, 1123, 1125, 1130, 1133, 1136, 1141, 1142, 1148, 1149, 1150, 1151, 1152, 1154, 1155, 1163,

30 1164, 1166, 1170, 1171, 1172, 1175, 1180, 1184, 1187, 1190, 1191, 1194, 1195, 1206, 1211, 1212, 1215. Application Example 3

Erysiphe graminis tritici (Mildew on wheat) . Curative spraying of young wheat plants. 5

Solvent : 10% acetone in water.

Emulsifier: Triton x-155, 100 ppm.

To prepare an appropriate composition of active

10 substance the active substance is dissolved in the specified solvent with emulsifier to the concentration desired. Further dilution is carried out by a solution containing 10% acetone in water and 100 ppm Triton X-155.

15 To test for curative activity young wheat plants are sprayed to leaf wetness with the composition of active substance 24 hours after the plants have been inoculated with mildew conidia by the brush method. After inoculation and until spraying the plants are

20 left at 18 C and 100% RH, and after spraying they are left in a growth chamber at 18 C and 70-80% RH.

8 Days after inoculation the activity of the substance is evaluated. A clear superiority in activi¬ ty in relation to the state of the art is shown by the

25 compounds according to the Examples Nos. 1003, 1009, 1024, 1032, 1042, 1050, 1053, 1055, 1061, 1063, 1074, 1075, 1081, 1083, 1100, 1101, 1105, 1108, 1112, 1126, 1127, 1128, 1129, 1133, 1134, 1150, 1164, 1170, 1173, 1176, 1177, 1180, 1190, 1191, 1192, 1200, 1204, 1205,

30 1218, 1223, 1224, 1228. Test results (EDg_Q) obtained ar_cording to Application

Examples 2 and 3 are surπrarized in the following Table 2

Table 2 : BIOLOGICAL TESTS

Comp , Puccinia Erysiphe Corp. Puccinia Erysiphe No. recondita graminis No . recondita graminis

(wheat) tritici (wheat) tritici (wheat) (wheat)

ED_an (ppm) ED_qn (ppm) ED_Qn (ppm) ED_qn (ppm)

'90 '90

A 128 64 B 128 1 C 256 1 1003 2 1006 32 1 1008 32 32 1009 32 64 2 1014 32 1 1019 32

64 1021 32 1141 128 1024 1142 64 1026 32 1148 64 1028 32 1149 64 1032 32 1 1150 32 1042 1 1151 64 1043 64 1152 16 1045 32 1154 64 1050 1 1155 64 1053 1 1163 32 1055 1 1164 32 0,5 1059 64 1166 32 1061 1 1170 32 1 1063 1 1171 32 1065 32 1172 64 1071 32 1173 0,5 1074 1 1175 32 1075 1 1176 4 1080 32 1177 1 1081 32 1 1180 ^' 64 2 1082 32 1184 64 1083 1 1187 64 1084 64 1190 32 < 2 1086 32 1191 16 0,5 1092 64 1192 1 1094 32 1194 32 1096 32 1195 64

1100 32 1 1200 1

1101 32 2 1204 2

1102 32 1205 2

1104 32 1206 32

1105 1 1211 32

1107 64 1 1212 32

1108 1 1215 32

1109 32 1218 2

1112 32 1223 1

1121 32 1224 < 2

1122 32 1228 < 2

1123 64

Claims

P A T E N T C L A I M S

1. Aminoethyl ketals , characterised by having the general formula I

R² and R³ each independently represents hydrogen, straight or branched chain alkyl having up to 10 carbon atoms, unsubstituted or alkylsubstituted cycloalkyl, alkenyl having up to 10 carbon atoms, aikynyl or un- substituted or alkylsubstituted cycloalkylalkyl, or R² and R³ when taken together with the nitrogen atom to which they are attached form a substituted or un¬ substituted heterocyclic ring which may optionally contain one or more additional hetero atoms selected from 0 and N, with the exception of the compounds falling under formula I which occur in Table 1 on pages 9-39 of EP 0 349 247 A2

2. A process for the preparation of aminoethyl ketals of the general formula I

wherein R¹, R² and R³ have the meanings defined in claim 1, characterised by reacting a ketal of the general formula II

wherein R¹ has the above defined meaning, and wherein Z represents an exchangeable electron-attracting group, with an amine of the general formula III

wherein R^ and R^J have the above defined meanings, optionally in the presence of a solvent and optionally in the presence of a catalyst, and optionally in the presence of an acid-binding agent in addition to a possible excess of the amine III.

3. A process according to claim 2, characterised by using a ketal of the general formula II, wherein Z represents a methanesulphonyloxy group or a chlorine or bromine atom.

4. An intermediate product for use in the process according to claim 3, characterised by having the general formula II

wherein R¹ has the above defined meaning, and Z repre¬ sents a methanesulphonyloxy group or a chlorine or bromine atom.

5. A starting material for the preparation of an intermediate product according to claim 4 of formula

II wherein Z represents a methanesulphonyloxy group, by reaction with methanesulphonyloxy chloride, charac- terised by having the formula IV

wherein R¹ has the above defined meaning.

6. A fungicidal composition, particularly a plant-fungicidal composition, and more particularly a cereal-fungicidal composition for combating mildew, rust and other significant foliage diseases, charac- terised by containing as an active component at least one compound selected from the aminoethyl ketals of formula I as defined in claim 1.

7. Use of an aminoethyl ketal of formula I as defined in claim 1 for combating fungi, particularly phytopathogenic fungi, and more particularly mildew, rust and other significant foliage diseases on cereals.

8. A method of combating fungi, particularly phytopathogenic fungi, and more particularly mildew, rust and other significant foliage diseases on cereals, characterised by allowing an aminoethyl ketal of formu¬ la I as defined in claim 1 to affect the fungi con¬ cerned and/or their biotope.

9. A process of preparing a fungicidal composi¬ tion, particularly a plant-fungicidal composition, and more particularly a cereal-fungicidal composition for combating mildew, rust and other significant foliage diseases, characterised by mixing an aminoethyl ketal of formula I as defined in claim 1 with one or more agents selected from extending agents, surface active agents and other conventional auxiliary agents.