IE46810B1 - Morpholine derivatives and their use as fungicides - Google Patents

Description

The nresent invention relates to new and valuable morpholine derivatives and their salts and molecular compounds and adducts, having a good fungicidal action, fungicides containing these compounds, and processes for combatting fungi with these compounds.

The use of N-tridecyl-2,S-dimethylmorpholine and its salts, molecular compounds and adducts as fungicides has been disclosed (German Patent 1,164,152, German Patent 1,173,722, German Laid-Open Application DOS 2,461,513).

We have now found that morpholine derivatives of the formula I \_ v ?;'3 Ά 15 ll R' 4 where R, R , Fr and R denote hydrogen, methyl or ethyl, and their salts, molecular compounds and adducts have a good fungicidal action The results tabulated in Examples 3-5 below show that the fungicidal action of compounds according to the invention is superior to that of commercial prior art morpholine derivatives.

Examples of salts are those wich inorganic or organic acids, e.g., chlorides, fluorides, bromides, iodides, sulfates, nitrates, phosphates, acetates, propionates and fumarates. Molecular compounds and adducts are formed for instance with acids cf surfactants, e.g., dodecylbenzenesulfonic acid.

If the new compounds are 2,6-dimethyl derivatives, they may be isolated as cis and trans isomers. The compounds may be manufactured for instance by reaction of a morpholine of the formula R1 R3 AA H-N 0 6 8 1ο where to R^ have the above meanings, e.g. 2,6-dimethylmorpholine, CH3 with 3-p-ιert-butylphenyl-2-methylpropanal having the formula -(/ x'V-CH2-CH-C^ CH- _ S CH,-CJ 1 in tne presence of a diluent, e.g., formic acid, at from 50° to 11.0 C. lhe preparation of the new compounds is illustrated by the following examples.

EXAMPLE 1 Synthesis of :,'-(3-p-tert-butylohenyl-2-nethyl-l-propvl)-cis2,t-dimethylmcrnholine 2,6-Dimethylmorpholine which has been obtained by sulfuric acid-catalyzed cyclization of diisopropanolamine is separated into the cis and trans forms by fractional distillation in a column packed with steel mesh coils. About 75 wtS of the 2,6-dimethylmorpholine is in the cis configuration, the remainder in the trans form. The isomers are separated by fractional distillation in a column having about 40 theoretical plates. The cis form distils as a 995 product at 30° to 3l°C and a pressure of 100 mm Hg. The trans form of 2,6-dimethylmcrpholine may be obtained under the same conditions at 33° to 39°C/1OO mm Hg as a more than product 575 g of 935 formic acid is placed in a stirred apparatus equipped with reflux condenser, thermometer and dropping funnel. Xhile stirring and cooling, 3^5 g of 995 2,6-cis-dimethylir.oroholine is then dripped in. The mixture is subsequently slowly heated on a water bath tc 70°C. Over a period of 4 hours, 612 g of p-p-tertbutylphenyl-2-methylpropanal is dripped into the reaction mixture, a temperature of approx. 100°C being maintained. Condensation proceeds with marked evolution of CO,. Upon conclusion of the reaction the mixture is kept for 2 hours at 100°C while stirring.

The excess formic acid is then distilled off under reduced pressure. Substantial seoaration of the formic acid is achieved under a water pump vacuum at 100 6 810 The base is liberated from the formate by dripping in 500 ξ of 402 aqueous caustic soda solution. The caustic soda solution is advantageously added at from 30° to 100°C to facilitate admixture of the amine phase which forms with the caustic phase. 2C0 g of toluene is added to depress the viscosity. After separation of the caustic phase, the organic phase is washed twice with water, each time with 250 g.

For further purification, the amine is fractionally distilled at 0.2 mm Kg in a distillation column having 5 trays. In addition to a small amount of first runnings (up to l43°C/0.2 mm Kg 50 g), there is obtained 805 g of N-(3-p-tert-butylphenyl)-2-methyll-propyl)-2,6-cis-dimet'nylmorpholine, which distils at 0.2 mm Kg between 143° and l46°c. According to gas-chromatographic analysis, the amine is more than 932 pure. With reference to aldehyde, the yield was 84.52.

To convert the compound to the hydrochloride, 30 g of the pure product is dissolved Ir. 50 g of ethanol which has been saturated with hydrogen chloride at room temperature. After cooling there is obtained 23 g of the hydrochloride (m.p. 220°C) in very pure form.

EXAMPLE 2 Synthesis of K-(3-p-tert-butylphenyl-2-methyl-l-propyl)-2,6trans-dimethylmorpholine While cooling with ice, 29 g of 2,6-trans-dimethylmorpholine 25 is introduced Into 70 g of 9θ« formic acid, While stirring, Hi g of 3-p-tert-butyIpheny1-2-methylpropanal is then added. The reaction mixture is heated for 6 hours at 1CO°C. Koon commencement of the reaction, very strong COg evolution takes place which drops noticeably after about; an hour. Further working up is effected as disclosed in more detail in Example 1, K-(3-p-tert-butyIpheny1-2-methyl-l-propy1)-2,6-trans-dimethylmorpnoline distils at l53°-lc9°C (5 mm Kg). The yield is ϋ 8 1 u -2 g (554 of theory, with reference to aldehyde). 11 g cf the amine is dissolved in 10 5 of ethyl acetate which has been saturated with anhydrous hydrogen chloride. The hydrochloride crystallites out upon cooling; m.p.: 165°C.

The other compounds according to the invention may be obtained analogously.

Examples of compounds according to the invention are given below r = c: CH, CH , 3 -Cii-Cn2_ Compound no. 1 r-:Q CH, b.o.: 123°C/O.C1 mm , __ . SO,H ce3 m.D.: 108°C CH, R-M 0 \_y \ CH, cis form ^CH3 R-’J 0 b.p.: 143-140°C/O.2 mm b.p.: l63-l6o°c/5 nm CH, trans form r\ R- 0 \ / .HC1 m.p.: 22CT cis form CHR-N .HC1 trans form -CH CH, 2 R· -m CH.

CH, R-N S ch3 R-iQ CHj /—\ R-N 0 \_y R· HC1 H^C )“λ R-N 0 H^C R-N 0 f % R-lZ~% caV /—fC2H5 HC1 R-N 0 .HOOC - CH -CHj HC - COOH cis form m.p.: 165°C b.p.: 123°C/0.02 mm b.p.: 133°C/0.05 mm b.p.: 125°C/0.02 am b.p.: 17O°C/5.O aa m.p.: 2O6°C b.p.: 145°C/O.3 mm m.p.: 172°C b.p.: 148°C/O.3 mm b.p.: 146-148°C/O.3 ma m.p.: 228°C m.p.: 174°C Ί Α υ ϋ 1 υ Ihe morpholine derivatives according to the invention and the fungicides containing then are particularly suitable for combatting olant diseases such as Zrysirhe rraninis in cereals, Ery sinhe cichoriacearum in Cucurbitaceae, foccsnhaera lenentricha in apples, 1'nci.nula necator in grapes ,Ery3inhe nolyroni in beans, Cnhaerotheca oanr.csa in roses, licrosnha^ra cuercl in oaks, 3-tryfis c in ere a in strawberries and grapes/'ycosphaerella musicola in bananas, Puccinia species (rusts) in cereals, hromyces aonendiculatus and ii. ohaseoli in beans, nemilela vastatrix in coffee, and Rhisoctonia solani. Therefore, they may be applied, for example to cereal plants (e.g. wheat and barley for protection against rust and/or mildew), bean plants, apple trees, grape vines, rose trees, cucurbitaceae plants, oak trees, strawberry plants, banana trees and coffee plants. They have a systemic action; they are not only taken up by the roots but also absorbed by the leaves, and are translocated in the plant tissue. They may be used to treat the plants after fungus attack has begun.

Application is effected for instance by watering, spraying, dusting, or disinfecting the plants or treating the seed with the morpholine derivatives.

When the morpholine derivatives are used to protect plants against fungus infection, the application rates are from 0.025 to 5 kg of active ingredient per hectare. For the surface protection of trees or fruit, the morpholine derivatives may also be used in combination with plastics dispersions in amounts of from 0.25 to 5/i, based on the weight of the dispersion. In general, the fungicidal compositions according to the invention contain from 0.1 to 95, preferably from 0.5 to 90, wt% of the morpholine derivative.

The morpholine derivatives may also be mixed with other, prior art, fungicides. In many instances, the spectrum of fungicidal action is increased; with a number of fungicidal compositions in uhe weignt ratio range of 1:10 to 10:1 synergistic effects also , -.e., „ne fungicidal action of the combination nroduct is occur & (j 3 i 0 greater than the effect of the individual components added toget Sxamnles of fungicides which may be combined with the morpholine derivatives of the invention are dithiocarbamates and derivatives thereof, e.g., sine dimethyldithiocarbamate manganese ethy1eneb is dith io c arb amat e zinc ethyleneb isd i th io carb amat e tetramsthyltniuram disulfide ammonia complex of zinc-O.'jN'-ethylene-bisdithiocarbamate) and H,:i'-polyethylene-cis-(thiocarbamoyl)-disulfide ammonia complex of zinc-(Ϊ;,Μ'-prcpylene-bisdithiocarbamate) and :i,ii'-pclypropylsne-b is-(thiocarbamoyl)-disulfide heterocyclic structures, such as ii-trichlor omethy 1th iot etrahydroph thalinide ii-trichloromethylthiophthalimide O'- (1,1,2,2-tetrachloroethyl thio)-tetrahy drophthalimide methyl l-(butylcarharaoyl)-2-benzimidazole carbamate 2-methoxycarbonylaminobenzimidazole 2,3-dihydro-5-carboxanilido-δ-methy1-1,U-oxathiin-t,4-dioxide 2.5- dihydro-5-carboxanilido-o-methyl-l,k-oxathiin -butyl-2-dimethylanino-4-hydrcxy-6-methylpyrimidine l,2-bis-(3-ethoxycarbonyl-2-thioureido)-benzene - j 2- b is - (3 -metho xy c arb ony 1) - 2-th io ure ido) -b enzene and various fungicides, such as dodecylguanidine acetate ii-dichlorofluororcethylthio-i?''-dimethyl-M-phenylsulfuric acid diamide 2,5-dimethylfuran-3-carboxylic acid anilide 2.5- damethylfuran-5-carboxylic acid cyclonexyl amide 2-iodcbensoic acid'anilide ί 6 a ι u 2- bror.oter.soic acid anilide 3- nitroisophthalic acid diisopropyl ester 1-<_ 1,2, k-triazolyl-l' )- ^1-(4' -chlcropher.oxy )J -3, 3-dimethylbutan-2-one 1—(1-imidazolyl)-2-allyloxy-2-(2,4-dichlorophenyl)-ethane piperazine-1, n-diy1-bis-l- (2,2,2-crichioroethyD-f ormamide 2,4,5,e-tetraenioroisophthalonitrile 1,2-dimethyl-3,5—iiphenylpyrascliniummethylsulfate.

Application ma?/ be effected for instance in the form of directly sprayable solutions, powders, suspensions, dispersions, emulsions, oil dispersions, pastes, dusts, broadcasting agents, or granules by spraying, atomizing, dusting, broadcasting or watering. The forms of application depend entirely on the purpose for which the morpholine derivatives are being used; in any case they should ensure a fine distribution of the morpholine derivative.

For the preparation of solutions, emulsions, pastes and oil dispersions to be sprayed direct, mineral oil fractions of medium to high boiling point, such as kerosene or diesel oil, further coal-tar oils, and oils of vegetable or animal origin, aliphatic, cyclic and aromatic hydrocarbons such as benzene, toluene, xylene, paraffin, tetrahydronaphthalene and alkylated naphthalenes, and hydrocarbon derivatives such as methanol, ethanol, propanol, butanol, chloroform, carbon tetrachloride, cyclohexanol, cyclohexanone, chlorobenzene and isophorone as well as strongly polar solvents such as dimethylformamide, dimethylsulfoxide, N-methylpyrrolidone and water, are suitable.

Aqueous formulations may be precared from emulsion concentrates, pastes, oil dispersions or wettable powders tv adding water. To prepare emulsions, pastes and oil dispersions the ingredients as such or dissolved in an oil or solvent may be homogenised in water by means cf wetting or dispersing agents, adherents or emulsifiers. Concentrates which are suitable for dilution with water may be prepared from the morpholine derivative, wetting agent, adherent, emulsifying or dispersing agent and possibly solvent or oil.

Examples of surfactants are: alkali metal, alkaline earth metal and ammonium salts of ligninsulfonic acid, naphthalenesulfonic acids, phenolsulfonic acids, alkylaryl sulfonates, alkyl sulfates, and alkyl sulfonates, alkali metal and alkaline earth metal salts of dibutylnaphthalenesulfonic acid, lauryl ether sulfate, fatty alcohol sulfates, alkali metal and alkaline earth metal salts of fatty acids, salts of sulfated hexadecanols, heptadecanols, and octadecanols, salts of sulfated fatty alcohol glycol ethers, condensation products of sulfonated naphthalene and naphthalene derivatives with formaldehyde, condensation products of naphthalene or naphthalenesulfonic acids with phenol and formaldehyde, polyoxyethylene octylphenol ethers, ethoxylated isooctylphenol, ethoxylated octylphenol and ethoxylated nonylphenol, alkylphenol polyglycol ethers, tributylphenol polyglycol ethers, alkylaryl polyester alcohols, isotridecyl alcohols, fatty alcohol ethylene oxide condensates, ethoxylated castor oil, polyoxyethylene alkyl ethers, ethoxylated polyoxypropylene, lauryl alcohol polyglycol ether acetal, sorbitol esters, lignin, sulfite waste liquors and methyl cellulose.

Powders, dusts and broadcasting agents may be prepared by mixing or grinding the morpholine derivatives with a solid carrier.

Granules, e.g., coated, impregnated or homogeneous granules, may be prepared by bonding the morpholine derivatives to solid carriers. Examples of solid carriers are mineral earths such as silicic acid, silica gels, silicates, talc, kaolin, Attaclay, limestone, lime, chalk, bole, loess, clay, dolomite, diatomaceous earth, calcium sulfate, magnesium sulfate, magnesium oxide, ground plastics, fertilizers such as ammonium sulfate, ammonium phosphate, ammonium nitrate, and ureas, and vegetable products such as ϋ d 1 Ο grain flours, bark meal, wood meal, and nutshell mea cellulosic powders, etc.

There may be added to the compositions or individual active ingredients oils of various types, herbicides, fungicides, r.ema5 tocides, insecticides, bactericides, trace elements, fertilisers, antifoams (e.g., silicones), growth regulators, antidotes and otner herbicidally effective compounds.

In the following experiments, the following prior art compounds v.’ere used for comparison purposes: Compound no.

C13H27'-’C^ (prior art) CH, CH, CH, C.,H,7-H 0 .CH,C00H D 27 χ_/ 3 CH3 (prior art) c„h27-O .CH, (prior art) CH, EXAMPLES 3 Leaves of wheat seedlings of the Jubilar variety grown in 2o pots are treated with aqueous emulsions consisting of 80S (wtS) of active ingredient and 20% emulsifier and dusted, after the sprayed on layer has dried, with spores of wheat mildew (Ervsiohe -reminds var. trltlcl). The plants are then placed in a greenhouse at from 2C'“ tc 22°C and 75 to SO. relative humidity. The extent the fungu has spread is determined after 10 days. 3 3 θ !2 Active·ingredient Lea? attack after spraying with liquors containing active ingredients in amounts of 0.006% 0.012% 0.0255 0.05S 1-2 1 0 1 0 1 0 0 ) 3-4 ) prior art 4 ) 2 0-1 0 0-1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 1 2 1 110 Control (untreated) = no attack, graduated down to 5 = surface of leaves completely covered by fungus.

EXAMPLE 4 Leaves of barley seedlings of the Eirlbecks Union variety grown in pots are treated as described in Example 3, and dusted with spores of barley mildew (Erysiphe graminis var. hordei).

Active ingredient Leaf attack, after spraying with liquors containing active ingredient in amounts of 0.006%0.012%0.025% orior art ) Control (untreated) 0-1 = no attack, graduated down to 5 = surface of leaves completely covered by fungus.

EXAMPLE 5 Leaves of wheat plants grown in pots are artificially infected with spores of leaf rust (Pucclnla recondita) and placed for 48 hours in a steam-saturated chamber kept at 20° to 25°C.

The plants are then sprayed with aqueous liquors containing a mixture, dissolved or emulsified in water, of 802 of the active ingredient and 202 of sodium lignin sulfonate, and placed in a greenhouse at from 20° to 22°C and 75 to 802 relative humidity.

The extent the fungus has spread is assessed after 10 days.

Active ingredient Leaf attack after spraying with liquor con1 taining active ingredient in amounts of 0.025_0.05_0.1 1 2-3 1-2 0 3 0 0 0 4 0 0 0 5 0 0 0 6 0 0 0 1 0 ·* X 0 0 0 20 0 0 0 7 ) 4 3 2 3 ) prior art 4 4 3 9 ) 4 3 3 Contr •ol (untreated) 4 = no damage, graduated down to 5 = surface of leaves completely 25 covered by fungus.

EXAMPLE 6 parts by weight of compound 5 is mixed with 10 parts by weight of N-methyln/-pyrrolidone. A mixture is obtained which is suitable for application in the form of very fine drops.

’ EXAMPLE 7 parts by weight cf compound 4 is dissolved in a mixture consisting of 80 parts by weight of xylene, 10 parts by weight of the adduct of 8 to 10 moles of ethylene oxide to 1 mole of oleic acid M-monoethanolamide, 5 parts by 'weight of the calcium salt of dodecylbensenesulfcnic acid, and 5 parts by weight of the adduct of 40 moles of ethylene oxide to 1 mole of castor oil. By pouring the solution into 100,000 parts by weight of water and uniformly distributing it therein, an aqueous dispersion is obtained containing 0.022 by weight of the active ingredient.

EXAMPLE 8 parts by weight of compound 3 is dissolved in a mixture consisting of 40 parts by weight of cyclohexanone, 30 parts by weight of isobutanol, 20 parts, by weight of the adduct of 7 moles of ethylene oxide to 1 mole of isooctylphenol, and 10 parts by weight of the adduct of 40 moles of ethylene oxide to 1 mole of castor oil. 3y pouring the solution into 100,000 parts by weight of water and uniformly distributing it therein, an aqueous dis15 pension is obtained containing 0,022 by weight of the active ingredient.

EXAMPLE 9 parts by weight of compound 4 is dissolved in a mixture consisting of 25 parts by weight of cyclohexanol, 65 parts by weight of a mineral oil fraction having a boiling point between 210° and 28O°C, and 10 parts by weight of the adduct of 40 moles of ethylene oxide to 1 mole of castor oil. By pouring the solution into 100,000 parts by weight of water and uniformly distributing it therein, an aqueous dispersion is obtained containing 0.022 by weight of the active ingredient.

EXAMPLE 10 parts by weight of compound 5 is well mixed with 3 parts by weight of the sodium salt of diisobutylnaphthalene-^-sulfonic acid, 17 parts by weight of the sodium salt of a ligninsulfonic acid obtained from a sulfite waste liquor, and 60 parts by weight of powdered silica gel, and triturated in a hammer mill. By uniformly distributing the mixture in 20,000 parts by weight of water, a spray liquid is obtained containing 0.15 by weight of the active ingredient.

EXAMPLE 11 parts by weight of compound 3 is intimately mixed with parts by weight of particulate kaolin. A dust is obtained containing 35 by weight of the active ingredient.

EXAMPLE 12 parts by weight of compound 4 is intimately mixed with a mixture consisting of 92 parts by weight of powdered silica gel and 3 parts by weight of paraffin oil which has been sprayed onto the surface of this silica gel. A formulation of the active, ingredient is obtained having good adherence.

' EXAMPLE 13 parts by weight of compound 3 is intimately mixed with parts of the sodium salt of a phenolsulfonic acid-urea-formalde- . hyde condensate, 2 parts of silica gel and 48 parts of water to give a stable aqueous dispersion. Dilution in 100,000 parts bj' 2o weight of water gives an aqueous dispersion containing 0.04 wtS of active ingredient.

EXAMPLE 14 parts of compound 4 is intimately mixed with 2 parts of the calcium salt of dodecylbenzenesulfonic acid, 8 parts of a 25 fatty alcohol polyglycol ether, 2 parts of the sodium salt of a phenolsulfonic acid-urea-formaldehyde condensate and 68 parts of a paraffinic mineral oil. A stable oily dispersion is obtained.

Claims (5)

1. A morpholine derivative of the formula where R 1 , R 2 , R^ and R^ each independently denote hydrogen, 5 methyl or ethyl, or a salt, molecular compound, or adduct thereof.

2. N-(3-p-tert-butylphenyl-2-methyl-l-propyl)-2,6-dimethylmorpholine.

3. N-(3-p-tert-butylphenyl-2-methyl-l-propyl)-2-methylmorpholine. 10 4· N-(3-p-tert-butylphenyl-2-methyl-l-propyl)-3-methylmorpholine. 5· N- (3-p-tert-butylphenyl-2-methyl-l-propyl)-morpholine. 6. W-(3-p-tert-butylphenyl-2-methyl-l-propyl)-2,2,6-trimethylmorpholine. 15 7. N-(5-p-tert-butylphenyl-2-methyl-l-propyl)-2,5-dimethylmorpholine. 8. N-(3-p-tert-butylphenyl-2-methyl-l-propyl)-3,5-dimethylmorpholine. 9. N-(3-p-tert-butylphenyl-2-methyl-l-propyl)-2,6-diethyl2o morpholine. 10. N- (3-p-tert~butylphenyl-2-methyl-l-propyl )-3,5-diethylmorpholine. 11 · W- (3-p-tert-butylphenyl-2-methyl-l-propyl )-cis-2,6-dimethylmorpholine. 25 12. A morpholine derivative as claimed in any of claims 1 to 11 in the form of a molecular compound or adduct with an •1 t> J 1 υ acid of a surfactant or in the form of a salt with an inorganic or organic acid. 13. A morpholine derivative as claimed in claim 12 in the form of its chloride, fluoride, bromide, iodide, sulfate, nitrate, 5 phosphate, acetate, propionate or fumarate salt or its dodecylbenzenesulfonic acid adduct or molecular compound. 14. A process for preparing a morpholine derivative as claimed in claim 1 wherein 3-p-tert-butylphenyl-2-methylpro~ panal of the formula CH, t 3 CH, I 3 CH10 CH 3 is reacted with a morpholine of the formula η ο χ » where R 4 , R , R 9 and R q have the meanings given in claim 1, in the presence of a diluent at a temperature of from 50° 15 to 110°C. 15. A morpholine derivative as claimed in claim 1 when prepared hy a process as claimed in claim 14, or a salt, molecular compound or adduct thereof. 16. The use of a compound as claimed in any of claims 1 to 20 13 or 15 as a fungicide (other than for application to human beings ). 17. A fungicidal composition comprising a solid or liquid carrier and a compound as claimed in any of claims 1 to 13 or 15.

4. 6 8 10 18. Λ fungicidal composition as claimed in claim 17 in the form of a solution, emulsion, paste or oil dispersion in an organic liquid to be sprayed direct or diluted with water for spraying. 19. A fungicidal composition as claimed in claim 17 as an aqueous formulation. 20. A fungicidal composition comprising a compound as claimed in any of claims 1 to 13 or 15 and a wetting or dispersing agent, adherent or emulsifier. 21. A fungicidal composition as claimed in claim 17 in the form of a dust, wettable powder, broadcastable composition or granules. 22. A fungicidal composition as claimed in any of claims 17 to 21 which contains a further fungicide. 23. A fungicidal composition comprising a compound as claimed in any of claims 1 to 13 or 15 and a further fungicidal compound listed herein. ; 2A. A process for preparing a fungicidal composition, wherein a solid or liquid carrier is mixed with a compound as claimed in any of claims 1 to 13 or 15. 25. A process for combatting fungi, wherein the locus to be protected against fungus attack (which locus is not a human being) is treated with a compound as claimed in any of claims 1 to 13 or 15. 2 ? . A process for combatting fungal attack in plants wherein the plants, or their seeds, are treated with a compound as claimed in any of claims 1 to 13 or 15. 27. A process ns claimed in claim 26 wherein the plants np- treated after fungus. attack, 28. A process as claimed in claim 26 or 27 wherein the plants are cereal plants, bean plants, apple trees, grape vines, cucurbitaceae plants, rose trees, oak trees, strawberryplants, banana trees, or coffee plants. 29. A process as claimed in claim 28 wherein wheat or barley plants are treated for protection against rust and/or

5. Mildew.