Technical field

The present invention relates to novel dithiocar¬ bamate derivatives, antimicrobial compositions comprising novel dithiocarbamate derivatives as active ingredients, novel compositions comprising the novel dithiocarbamate derivatives together with known active ingredients, use of the same against damages caused by microorganisms and process for the preparation of the novel guanidine derivatives.

Background art

To avoid economic losses caused by microorganisms in various products, especially for the control of different microorganisms pathogenic to plants, dithio- carbamate compounds are used (British patent specifica¬ tions Nos. 840,211 and 99,264; US patent specifications Nos. 1,972,961, 2,457,674, 3,050,439, 2,317,765, 3,248,400, 2,504,404, 2,710,822, 3,379,610, 2,974,156 and 1,972,961) . There are known fungicidal and bactericidal com¬ positions the active ingredient of which is a compound carrying a guanidine functional group or the salt thereof (US patent specification No. 2,867,562; Mitchell et al., Bull. Agric. Chem. Soc. Japan, 18-19, 1955). Though these compositions are effective, their scope of activity is limited. Their use was driven into the background due to their low therapeutic indices, and moreover to acquired resistance of the plant pathogenic microorganism, surviv¬ ing for more vegetation periods which could have occurred in their populations due to the frequent use of the said

compositions (Ross, R.G. and Newberry, R.J. : Tolerance o Venturia inaequalis to dodine in Nova Scotia, Canadia Plant Disease Survey, 57, 57-50 (1971); Oros G. : Effect of benomyl on Venturia inaequalis isolates resistant to benomyl. Acta Phytopathologica Academiae Scientiaru Hungariae, Vol. 16, 31-40 (1981)).

Published German patent application No. 2,144,123 relates to fungicidal and microbicidal composition comprising a complex formed from a guanidine base and a metal salt of dimethyldithiocarbamic acid.

Detailed description of the invention The compounds of the present invention exhibit especially good activity compared to the complex described in published German patent application No. 2,144,123, which is the closest structural analog, but antimicrobial activity of the new compounds of the general formula

D>M-G*Y (I) is better and their scope of activity is broader, thus their therapeutic indices are higher than that of the former one.

In the general formula (I)

D stands for one or more moieties comprising di- thiocarbamic functional groups of general formula R ¹ R ² NCS2, where R ¹ and R ² are independently alkyl having 1 to 8 carbon atoms or together form an C4-C7 alkylene which may contain one or more heteroatoms;

M is a metal atom having atomic number higher than 20 and atomic volume less than 20 cm ³ , for example, selected from the following metals: manganese, iron, cobalt, nickel, zinc, copper, molybdenum, rhodium, silver, tin, samarium, platinum, gold, mercury and lead; G stands for a moiety carrying the guanidine functional group, e.g. arginine, blasticidine, alkyl-

- 3 -

guanidine having 1 to 20 carbon atoms, streptomycin, 2- -benzthiazolyl guanidine, preferably bis (8-guanidino)- -octylamine, alkylguanidine having 3 to 20 carbon atoms, more preferably dodecylguanidine, Y is a moiety carrying an acidic function and may be an inorganic or organic acid or a derivative thereof, such as mineral acids (such as phosphoric acid, phosphonic acid and phosphinic acid and the derivatives thereof, hydrochloric acid, sulfuric acid, boric acid, nitric acid) , organic carboxylic acids, e.g. the aliphatic or aromatic mono-, di- and polycarboxylic acids, e.g. the alkane carboxylic acids of 1 to 20 carbon atous (such as formic acid, acetic acid, propionic acid, stearic acid, pyruvic acid, lactic acid, benzoic acid, o-methyl benzoic acid, oxalic acid, tartaric acid, citric acid, succinic acid, adipic acid, ethoxyacetic acid, glucuronic acids, salicylic acid, cinnamic acid, deoxycholic acid, 3-(4- chlorophenyl)-3-(3,4-dimethoxyphenyl) acrylic acid, allo- furanoic acids, etc.). Y may also represent an organic derivative of phosphoric acid, phosphonic acid or phos¬ phinic acid, such as a phosphatidyl derivative, an aikylhydrophosphonic acid or 0-[l-(4-chlorophenoxy)-3,3- dimethyl-1-(1,2,4-triazol-l-yl)-2-but-2-yl) ]-P-(2-carb- oxyethyl)-P-methyl phosphinate, or an organic sulphate, such as dodecyl sulphate, Y may also represent a sulphonic acid, benzylamino benzene sulphonic acid, lignine sulphonic acid, 4-dimethylamino benzene diazo- sulphonate; a dithiocarbamic acid derivative, e.g. an alkyl or dialkyl dithiocarbamic acid, such as methyl-, ethyl- , diethyl-, dimethyl- or isopropyl dithiocarbamic acid, 1,4-butylenedithiocarbamic acid, etc. Y may also represent a phenol derivative, e.g. 2'-(2,4-dichloro- phenoxy)-4'-chlorophenol, 2-(l-methyl-heptyl)-4,6- dinitrophenol, 2,4,5-trichlorophenol, 2-sec-butyl-4,6- dinitrophenol, 2-(l,1-dimethylethyl)-4,6-dinitrophenol

etc.

Variations in the structure of the acid moiety can significantly increase the effectiveness of prepara- tions, as well as the therapeutic indices.

The compositions comprising the compounds of the general formula (I) may be used in agriculture, horticulture, forestry, pomiculture, viticulture for the prevention and treatment of microbial infection, however, they are also useful for the protection of any product subjected to microbial infection or biodeterioration.

The further object of the present invention is a process for the preparation of compounds of the general formula (I)

D'M-G'Y (I)

wherein D, M, G and Y have the meaning as mentioned above. The compounds of the general formula (I) are prepared by

A) reacting a guanidine derivative of the general formulaY-G (wherein Y and G are the same as defined hereinabove) with dithiocarbamate derivative of the general formula (II)

D-M (II)

(wherein D and M are the same as defined hereinabove) , or B) reacting a guanidine derivative salt Y-G-M

(wherein Y, G and M are the same as defined herein above) with a dithiocarbamate derivative of the general formula (III)

(R ¹ R ² NCS ₂ ) _n A (III)

(wherein R ¹ and R ² are the same as defined hereinabove, n is 1 to 3, A represents a mono- or polyvalent cation), or

C) reacting a mixture of a guanidine derivative of formula G (the meaning of which is the same as defined hereinabove) , a compound of formula Y carrying an acidic function (the meaning of which is the same as defined hereinabove) and a dithiocarbamate salt of the general formula (III) with M metal (which are the same as defined hereinabove) containing salt,

D) reacting a guanidine derivative of formula G (wherein G is the same as defined hereinabove) with a dithiocarbamate derivative of the general formula (II)

D-M (II)

(wherein D and M are the same as defined hereinabove) , and reacting the product with Y (wherein Y is the same as defined hereinabove) .

The compounds of formulae (II) and (III) used as starting materials in processes A to D are known and they can be prepared according to known methods.

The antimicrobial compositions according to the present invention comprise at least one compound of the general formula (I) as active ingredient optionally together with one or more other active ingredients when they are used in horticulture, agriculture, forestry, viniculture or pomiculture or when they are used in processes the aim of which is the supression of microorganism populations causing damages in products and materials (of n atural or synthetic origin) subjected to biodeterioration. These pesticidal compositions are especially useful for the supression of phytopathogenic microorganism populations (bacteria and fungi) attacking

different parts of the living plant (e.g. leaf, stem, root, tuber, fruit and bulb) , seed or living in the soil or these compositions can be used for the killing the propagation material of the same microorganisms damaging the cultivated plants.

In addition, the compounds of the general formula (I) are also useful for the protection of products and materials (e.g. leather, paper, wood, stored fodders and foodstuffs) subjected to biodeterioration. The compounds of the general formula (I) exhibit an excellent protective activity when used either before the infection or after the appearance of the symptoms of the disease (or detection of the microorganism responsible for the optional damage) . They are very well tolerated by the plants in therapeutic doses. They are resistant to physical (moisture, heat, light, etc.) and chemical (pH, vapours, etc.) effects under the conditions characteriz¬ ing the proposed scope of use, thus they can preferably exhibit their effect for a longer period when materials or products of natural or artificial origin, subjected to biodeterioration, are treated (e.g. during storage) with the compositions of the present invention.

The suitable amount of the compositions comprising at least one compound of the general formula (I) as active ingredient to be applied may vary according to the aim and conditions of the intended use.

The antimicrobial compositions according to the present invention exhibit their protective activity when they comprise the compounds of the general formula (I) in a dose of 5 to 500 mg calculated for 1 litre of spray, sprinkling or washing solution. Preferably 5 to 5000 g of compound of the general formula (I) has to be applied in suitable manner (spraying, sprinkling, dusting, incorporation into soil, etc.). When propagating materials (seeds, tubers,

cuttings, etc.) are treated, the preferable amount of the active ingredient is 50 to 3000 mg of compound of the general formula (I) calculated for 1 kg of propagating material or for 1 kg of medium (liquid or solid diluent, etc.) used for the treatment.

When the surface or tissues of plants subjected to biodeterioration or natural or synthetic materials and products subjected to biodeterioration are treated, the proposed dose is 1 to 500 μg of compound of the general formula (I) calculated for 1 cm ² of the surface to be treated or 1 to 1000 mg of compound of the general formula (I) calculated for 1 kg of the tissue, product or material to be treated, depending on the conditions of application. The antimicrobial compositions according to the present invention can be formulated in different forms, e.g. solutions, emulsions, dusts, granules, microcapsules, etc. (wp, ec, lw, ulw, fw, g, sd) and they can be used or dispersed, respectively, (e.g. by spraying, dusting, immersing, spreading, etc.) for preventing or reducing the damages caused by microorganisms in the medium or on the surface to be protected (e.g. leaves, foliage, flowers, fruit, bark, propagating material, wood, paper, leather, horn, easily degradable polymers, varnishes, etc. or boxes, containers, pots, etc. used for the storage, transport thereof.

In order to achieve the above aim the active ingredients can be dissolved or dispersed by conventional methods in liquid or solid carriers (diluents) in case of necessity in the presence of surface-active agents, optionally together with other biologically active ingredients.

The compositions of the present invention comprise 0.001 to 95 % by weight of at least one compound of for-

NOT FURNISHED AT TIME OF PUBLICATION

active ingredients (e.g. antibacterial, fungicidal, acaricidal, pesticidal, herbicidal and plant growth regulating agents) . The use of active ingredient mixtures is proposed in order to improve the activity or to broaden the scope of activity of the composition.

The antimicrobial compositions according to the present invention are prepared by dissolving or dispers¬ ing or formulating by an other conventional method at least one compound of the general formula (I) in the presence of appropriate carriers and excipients, op¬ tionally surface active additives (dyes, especially in the case of dressing agents) optionally together with one or more known active ingredients.

The antimicrobial compositions according to the present invention can be used in horticulture, agriculture, forestry, viniculture or pomiculture or in processes which aim at the supression of microorganism populations causing damages in crops and materials (of natural or synthetic origin) subjected to biodeteriora- tion in the conventional method.

Their use is especially useful against the follow¬ ing plant pathogens or pro- and eucaryotic microorganisms damaging materials subjected to biodeterioration: Gram negative (Agrobacterium spp., Erwinia spp., Pseudo onas spp., Xantho onas spp.) and Gram positive (Bacillus spp., Corvnebacterium spp., Strepto yces) bacteria; swarm-sporeal fungi (Spongospora sp., Plasmodiophorales) ; Olpidium sp. , (Chytridiales) ; Aphano yces sp. (Saprolegniales, Oomycetes); Pythium spp. (Peronosporales, Oomycetes), Phythophthora spp. (Peronosporales, Oomycetes) , Plasmopara spp. (Peronosporales, Oomycetes) , Sclerospora spp. (Peronosporales, Oomycetes) ; Pseudo- peronospora spp. (Peronosporales, Oomycetes)); conidiosporangial fungi (Peronospora spp. (Peronosporales,

Oomycetes)), βremia spp. (Peronosporales, Oomycetes), Albugo spp. (Peronosporales, Oomycetes) ; yoke-sporeal fungi (Mucor spp. (Mucorales, Zygomycetes) , Rhizopus spp. (Mucorales) ) ; ascomyctes fGeotrichu spp. (Endomycetales, Ascomycetes) , Taphrina spp. (Taphrinales, Ascomycetes) , Elsinoe spp. (Myrkingiales, Ascomycetes), Phyalospora spp.

(Dothideales, Ascomycetes) , Diodymella spp.

(Dothideales) ; Pleospora spp. (Pleosporales, Ascomycetes) Venturia spp. (Pleosporales), Erysiphe spp. (Erysiphales, Ascomycetes) , Microsphaera spp. (Erysiphales) , Uncinula spp. (Erysiphales) , Sphaerotheca spp. (Erysiphales) , Nectria spp. (Hypocreales, Ascomycetes) , Rosellinia spp. (Hypocreales) , Caetomium spp. (Sphaeriales, Ascomycetes) , Ceratostomella spp. (Sphaeriales) , Guinardia spp. (Sphaeriales) , Mvcosphaerella spp. (Sphaeriales) , Valsa spp. (Sphaeriales) , Diaporthe spp. (Sphaeriales) , Endothia parasitica (Sphaeriales) , Lophoder rm iu spp. (Phacidiales, Ascomycetes) , Sclerotinia spp. (Helotiales, Ascomycetes) , Botryotinia spp. (Helotiales) , Fabrea spp. (Helotiales, Ascomytes) ) ; basidial fungi (Rhizoctonia solani (Polyporales, Basidio- mycetes) , Tra etes spp. (Polyporales), Crotonarium sp. (Uredinales, Basidiomycetes) , Uromyces spp. (Uredinales) , Puccinia spp. (Uredinales), Ustilago spp. (Ustilaginales, Basidiomycetes) , Sorosporium spp. (Ustilaginales) , Tilletkia spp. (Ustilaginales), Urocvstis spp.

(Ustilaginales) , Graphiola sp. (Ustilaginales) ; and conidial fungi (Phyllosticta spp. (Sphaeropsidales, Deuteromycetes) , Phoma spp. (Sphaeropsidales) , Phomopsis spp. (Sphaeropsidales) , Dothiorella spp. (Sphaero¬ psidales, Cytospora spp. (Sphaeropsidales) , Ascochvta spp. (Sphaeropsidales) , Sphaeropsis spp. (Sphaero¬ psidales) , Diplodia spp. (Sphaeropsidales) , Botrvodi- plodia spp. (Sphaeropsidales), Colletotrichum spp.

(Melanconiales, FDeuteromycetes) , Oidium sp. (Moniliales, Deuteromycetes) , Aspergillus spp. (Moniliales) , Penicillium spp. (Moniliales) , Botrytis spp. (Moni¬ liales) , Verticilliu spp. (Moniliales) , Trichotecium spp. (Moniliales), Piricularia spp. (Moniliales), Cerco- sporella spp. (Moniliales) , Thielaviopsis basicola spp. (Moniliales) , Nigrospora spp. (Moniliales) , Cladosporium spp. (Moniliales) , Helminthosporium spp. (Moniliales) , Alternaria spp. (Moniliales) , Stemphylium spp. (Moniliales), Fusarium spp. (Moniliales)).

The compositions comprising at least one compound of the general formula (I) are effective against pathogenic microorganisms deriving from other infected plants or from infected soil, spreading with seeds, propagating materials, water, air or agricultural utensils.

Their use is especially useful for the protection of field plants (cereals, leguminous plants, Jerusalem artichoka, potato, hoed plants, grain crops, fodder plants, oil plants, Spanish potato, taro (Xanthosoma spp.) etc.) industrial plants (sugar beet, sugar-cane, cotton, tobacco, hemp, flax, etc.) vegetables (onion, paprika, cabbage, tomato, lettuce, carrot, etc.), fruits (pomiferous plants, stone-fruits, bacciferous plants, lemon and orange, pineapple, banana, avocado, mango, grape, strawberry, pomegranmate, fig, etc.), ornamental plants, spices and herbs (agave, asparagus, azalea, begonia, cyclamen, gladolus, tulip, hyacinth, hyacinth tulip, gerbera, rose, ahonia, carnation, cactuses, coniferous plants, hop, horse radish, lavender, sage, henbane, etc.) and propagating materials prepared by biotechnological way.

In addition, the compounds of the general formula (I) are useful for the protection of materials (e.g. timber, leather, paper, wrapping materials, etc.) and

products (e.g. fruits and other plant parts intended fo consumption or industrial use, detergents, health-car agents, cosmetics, varnishes, easily degradable polymers, etc.) subjected to biodeterioration during storage or transportation.

The compounds of the general formula (I) can als be used together with other known pesticides (insecticides, fungicides, safeners or other protective agents) . When the said mixture is used, a synergistic protective effect, exceeding the additional protective effect, may also occur.

The efficacy of the compositions comprising the compounds of the general formula (I) can be improved or the scope of activity of the same can be broadened by the addition of other antimicrobial agents. The use of the following, known active ingredients or the analogues thereof may be useful: aldimorph, 3-acetyl-2-hydroxy-6-methyl-4H-piran-4- -on, anilazine, l-allyloxy-2-(2',4'-dichlorophenyl)- -ethyl)-imidazole, anorganic polysulfides, azithiram, benquinox, benalaxyl, biphenyl, binapacryl, Bordeaux mixture, benomyl, benodanyl, biloxazole, S-benzyl-0,0-di- isopropyl-phosphorothioate, blasticidin, bronopol, buthiobate, bupyrimate, biphenyl, bitertanole, 4-butyl- -4H-l,2,4-triazole, chlorofenazole, carbamorph, cycla- furamide, cipendazole, cimoxanyl, cyclohexamide, cyprofurame, dichlorobutazole, 2,3-dihydroxy-5-phenyl- 1,4-dithiin-l,1,4,4-tetroxide, 2,3-dichloro-N-(4-fluor- phenyl)-maleinimide, dimethomorph, N-3,5-dichlorophenyl- succinimide, dimethbenzazole, dithianon, dimethirimol, dibromosalicyl aldehyde, 2,4-dinitrophenyl-thiocyanate, o-dihydroxybenzene, dichlorophen, dinobuton, dinocap, di- chloran, diclon, dodine, dodemorph (and the salts thereof), dichlorofluanid, o-(2,6-dichloro-4-methyl- phenyl)-0,0-dimethyl-thiophosphate, dithalimphos,

drazoxazolone, ( 2 * ,4'-dichlorophenyl)-2-hydroxy-4-chloro- phenyl ether, dazomet, dichlozoline, decafentin, dinocton, 1,3-dichloro-l,1,3,3-tetrafluoro-2-propanediol, 2,3-di- hydro-5-phenyl-l,4-dithiin, 1,1,4,4-tetroxide, ediphenphos, sulfur, ethaconazole, etridiazole, ethirimol, ethem, furcarbanyl, fosetyl-Al, fuberidazole, fenpropimorph, fenarimol, fluotrimazole, furmethamide, fenfuram, fenpropidin, flutolanyl, fluthirafol, 2- -phenylphenol, fenapronyl, furadantine, furazolidone, furalaxyl, furophanate, phentino hydroxide, phentino acetate, phenol, fenitropan, folpet, fenapanyl, grizeofulvine, glycophene, glyotoxin, glyodin, guazatine (and the salts thereof) , hexachlorobenzene (HCB) , halacrinate, hexaconazole, hymexazol, 2-heptadecyl-l-(2- -dihydroxyethyl)imidazolinone, l-(8-hydroxy-5-quinolin- -yl)-ethanon (and the salts thereof), imazalyl, iprodione, iprobenphos, N-isoxazolyl-5-yl-N-(2,6-xilyl)- alanine methylester, isoprothiolane, inesine, 2-chloro-N- (2-cynoaethyl)aceta ide, 5-chloro-7-bromo-8-hydroxy- quinoline (and the salts thereof), l-chloro-2,4-dinitro- naphtalene, l-chloro-2-nitro-propane, 5-chloro-4-phenyl- l,2-dithiol-3-on, 3-(4-chlorophenyl)-5-methyl-2-thioxo-4- thiazolidinone, chloroquinox, chlimbazole, chloro- amphenycole, 4-(3-chlorophenylhydrazono)-3-methyl-5- isoxazolone, carbendazim, 2-(carboxanilido)-3-methyl-5- a inothiazol, carboxin, chloranyl, chlorotalonyl, chloroneb, chlozolinate, m-cresyl acetate, captane, captafol, kitazin, kasugamycin, chlotrimazol, keta- konazol, methfuroxam, mylneb, methalaxyl, miconazole, metam, mezineb, mankouzeb, maneb, methiram, milneb, miclobutanyl, mebenyl, mecarbincid, mucochloric acid an¬ hydride, iclozoline, metazaxolone, 2-methylene-3-(m- -nitrophenyl)succinimide, nitrostyrene, nitrotal-iso- propyl, nabam, 5-nitro-furfurylaldoxim (I) , 5-nitro- furfurylaldoxim (II) , nuarimol, nystatin, omedine, (and

- 14 -

the salts thereof), ofurace, oxadixyl, oxyquinolin (an the salts thereof) , octylinone, oxycarboxine, paclo butrazole, pentachloronitrobenzene, pimaricine, propioneb, prochloraz, propiconazol, procimidone, pro- thiocarb, propamocarb, pyroxifur, penconazol, pencicurone, pyridine nitrile, pyroxichlor, quinauzamide, quinonamide, quinomethionmate, rabenzazole, copper(I) oxide, copprer phenylsalicylate, sec-butylamine, salicyl anilide, streptomycine, sultropen, tolylfluanide, tri- flumizole, thiraro, thiabendazole, thioquinox, tridemorp (and the salts thereof), triphorine, 1,2,4,5-tetrachloro 3-nitrobenzene, toclophos-methyl, thiophanate-methyl, thiophanate-ethyl, triamphos, 2,4,6-trichlorophenol, 2,4,5-trichlorophenol, trimorphamide, triadimefon, tria¬ dimenole, tricyclazole, 4,5,6,7-tetrachlorophtalide, tris(l-dodecyl-3-methyl-2-phenyl-benzimidazolium)ferri- cyanide, triarimol, validamycine, vinclozoline, N-(2,6- -xylyl)-2-methoxy-N-(tetrahydro-2-oxo-furanyl)-acetamide, 2,4-xylenyl, ziram, zineb. From the above compounds the derivatives of benz- imidazole, imidazole, triazole, piperazine, acetanilide, carboxanilide, morpholine; nitroaro atic compounds and antibiotics can be used in an especially useful way in a mixture formed with the compounds of the present inven- tion (see Table 1) . The application of the said mixtures can result in several advantages for the user.

A significant synergistic increase of activity was found when the compounds of the present invention were used together with the following known compounds (see Table 2 and Table 3) :

B + 6 ( 1:4) Plasmopara halstedii on sunflower A + 1 + 27 (11:4:4) Aspergillus niger, Penicillium spp. , Fusarium spp. , Botrytis spp., Pseudomonas spp., Peronospora destructor on

onion

A + 7 + 37 1:2 1)

A + 1 + 32 9:4 7) Erysiphe graminis on wheat

A + 37 2:3 II

A + 7 + 37 1:2 1) It

A + 23 1:1 It

A + 8 + 23 6:2 3) II

B + 8 + 37 6:2 3) II

A + 23 + 7 1:1 7) II

F + 23 3:2 II

G + 23 3:2 II

B + 23 + 41 12:8 8) II

F + 23 + 41 12:8 8) II

A + 42 5:3 II

A + 23 + 42 5:1 3) II

A + 14 2:1 II

B + 28 7:3 II

R + 23 1:1 •I

R + 23 7:3

A + 26 2:3 Phythium ultimum on pea

A + 20 2:3 Phythium ultimum on kohlrabi

A + 26 2:3 Oidium sp. on tomato

A + 39 3:1 Rosellinia necastrix on pomegranate

A + 2 3:2 Pythium spp. , Fusariu spp. Rhizoctonia sp.

A + 1 + ; 2 3:1:1) II

A + 26 + 42 3:1:1) Pythophtora infestans on tomato

Table 1 Synergetic antimicrobial compositions containing dithiocarbamate derivatives of formula (I) iDΗOΥl G = 1-dodecylguanidine

D'M _' G _' Y Added components

No. M y first second

1. Zn acetic acid + Aldimorph

2. Zn acetic acid + Benalaxyl

3. Zn acetic acid + Benomyl

4. Zn acetic acid + Buthiobate

5. Zn acetic acid + Carbendazim

6. Zn acetic acid + Cycloheximid

7. Zn acetic acid + Cymoxanil

8. Zn acetic acid + Diethofencarb

9. Zn acetic acid + Dinocap

10. Zn acetic acid + Dodemorph

11. Zn acetic acid + Etridazole

12. Zn acetic acid + Fenpropimorph

13. Zn acetic acid + Fentinhydroxid

14. Zn acetic acid + Hymexazole

15. Zn acetic acid + Kasugamycin

16. Zn acetic acid + Metalaxyl

17. Zn acetic acid + Myclobutanil

18. Zn acetic acid + Nystatin

19. Zn acetic acid + Ofurace

20. Zn acetic acid + Oxadixyl

21. Zn acetic acid + Polyoxin Al

22. Zn acetic acid + Prochloraz

23. Zn acetic acid + Propiconazole

21. Zn acetic acid + Propiconazole

22. Zn acetic acid + Triadimefon

23. Zn acetic acid + Thiabendazole

24. Zn acetic acid + Tridemorph

25. Zn acetic acid + Triforin

Table 1 (continuation A)

G = 1-dodecylguanidine

D _' M'G-Y Added components

No. M y first second

26. Zn acetic acid + Thiophanate-Me

27. Zn acetic acid + Benalaxyl Cymoxanil

28. Zn acetic acid + Ofurace Cymoxanil

29. Zn acetic acid + Oxadixyl Cymoxanil

30. Zn acetic acid 4- Etridiazole Dimetomorph

31. Zn acetic acid + Benomyl Myclobutanil

32. Zn acetic acid + Benomyl Polyoxin AL

33. Zn acetic acid + Carbendazim Pyrazophos

34. Zn acetic acid + Carbendazim Dinocap

35. Zn acetic acid + Carbendazim Furazolidon

36. Zn acetic acid + Carbendazim Prochloraz

37. Zn acetic acid + Benomyl Diethofencarb

38. Zn acetic acid + Carbendazim Diethofencarb

39. Zn acetic acid + Thiabendazole Diethofencarb

40. Zn acetic acid + Thiophanate-Me Diethofencarb

41. Zn acetic acid + Carbendazim Propiconazole

42. Zn acetic acid + Carbendazim Myclobutanil

43. Zn acetic acid + Benomyl Myclobutanil

44. Zn acetic acid + Carbendazim Fentinacetate

45. Zn acetic acid + Carbendazim Fentinhydroxid

46. Zn acetic acid + Tiaphanate-Me Fentinhydroxid

47. Zn acetic acid + Carbendazim Tridemorph

48. Zn acetic acid + Carbendazim Dodemorph

49. Zn acetic acid + Carbendazim Fenpropimorph

50. Zn acetic acid + Carbendazim Cycloheximid

51. Zn acetic acid + Carbendazim Polyoxin AL

52. Zn acetic acid + Carbendazim Nystatin

53. Zn acetic acid + Carbendazim Triforin

54. Zn acetic acid + Metalaxyl Aldimorph

55. Zn acetic acid + Carbendazim Fenarimol

Table 1 (continuation B)

G = 1-dodecylguanidine

D _' M _' G-Y Added components

No. M Y first second

56. Zn acetic acid + Benomyl Triadimefon

57. Zn acetic acid + Benomyl Benalaxyl

58. Zn acetic acid + Metalaxyl Tridemorph

59. Zn salicylic acid + Carbendazim

60. Zn o-toluic acid + Carbendazim

61. Zn DDC + Carbendazim

62. Zn lactic acid + Carbendazim Triforin

63. Zn o-toluic acid + Carbendazim Triforin

64. Zn DDC + Carbendazim Triforin

65. Cu acetic acid + Benalaxyl

66. Cu acetic acid + Carbendazim

67. Cu acetic acid + Cymoxanil

68. Cu acetic acid + Ciethofencarb

69. Cu acetic acid + Kasugamycin

70. Cu acetic acid + Ofurace

71. Cu acetic acid + Oxadixyl

72. Cu acetic acid + Polyoxin AL

73. Cu acetic acid + Pyrazophos

74. Cu acetic acid + Streptomycin

75. Cu acetic acid + Benalaxyl Cymoxanil

76. Cu acetic acid + Ofurace Cymoxanil

77. Cu acetic acid + Oxadixyl Cymoxanil

78. Cu acetic acid + Carbendazim Pyrazophos

79. Cu acetic acid + Benomyl Diethofencarb

80. Cu acetic acid + Carbendazim Diethofencarb

81. Cu acetic acid + Thiabendazole Diethofencarb

82. Cu acetic acid + Tiophanate-Me Diethofencarb

83. Cu acetic acid + Carbendazim Triforin

84. Cu acetic acid + Carbendazim Polyoxin AL

85. Cu acetic acid + Carbendazim Nystatin

- 19 -

Table 1 (continuation C)

G = 1-dodecylguanidine

D' •M _' G _' Y Added components

No. M Y first second

86. Cu acetic acid + Carbendazim Nystatin 87. Mn acetic acid + Carbendazim

Table 1 (continuation D) G = 1-dodecylguanidine

D-M _' G _' Y Added components

No. M first second

88. 49. Zn acetic acid + Imazalyl 89. 49. Zn acetic acid + Carbendazim

90. 49. Zn acetic acid + Carbendazim Imazalyl

91. 49. Zn acetic acid + Thiabendazole

92. 49. Zn acetic acid + Thiabendazole Imazalyl

The testorganisms used were:

Plasmopara halstedii

Ervsiphe αraminis

Pythium ultimum Phvtophthora infestans

Venturia inaequalis

Fusarium oxysporum

Rosellinia necatrix Oidium sp. (Moniliales, Deuteromycetes).

Table 2 Dimethyldithiocarbamate derivatives of the general formula (I) exhibiting antimicrobial activity

D _n -M _' G«Y (I)

Code M

A dodecyl-guanidine acetic acid methyl methyl Zn 2 B dodecyl-guanidine acetic acid methyl methyl Cu 2 C dodecyl-guanidine acetic acid methyl methyl Mn 2 D dodecyl-guanidine acetic acid methyl methyl Fe 3 E dodecyl-guanidine o-toluic acid methyl methyl Zn 2 F dodecyl-guanidine lactic acid methyl methyl Zn 2 G dodecyl-guanidine dimethyldithio- methyl methyl Zn 2 carbamic acid

H bis(8-guanidine)- acetic acid methyl methyl Zn 2

-octylamine

I dodecyl-guanidine stearic acid methyl methyl Zn 2 J dodecyl-guanidine deoxycholic acid methyl methyl Zn 2 K dodecyl-guanidine dodecylsulphonic methyl methyl Zn 2 acid dodecyl-guanidine ethylphosphonic methyl methyl Zn 2 acid

M dodecyl-guanidine dodecylsulphate methyl methyl Zn 2

N dodecyl-guanidine acetic acid 1,4-butylidene Zn 2

O dodecyl-guanidine acetic acid methyl methyl Ag 1 P bis(8-guanidine)- acetic acid methyl methyl Mn 2

-octylamine

R dodecyl-guanidine salicylic acid methyl methyl Zn 2

S dodecyl-guanidine 2 '-(2,4-dichloro- methyl methyl Zn 2 phenoxy)-4'- chlorophenole

Table 2 (contd. )

D _n -M-G-Y (I)

Code M

T dodecyl-guanidine 4-dimethylamino- methyl methyl Zn benzenediazosuolphonate dodecyl-guanidine 2-(l-methyl- methyl methyl Zn heptyl)-4,6-

-dinitrophenol V dodecyl-guanidine acetic acid ethyl methyl Zn 2 H dodecyl-guanidine 3-(4-chloro- methyl methyl Zn 2 phenyl)-3-(3,4- -dimethoxyphenyl)- -acrylic acid dodecyl-guanidine 2-(l-methyl- methyl methyl Mn -heptyl)-4,6- -dinitrophenol dodecyl-guanidine 0-[l-(4-chloro- methyl methyl Zn phenoxy)-3,3- -3,3-dimethyl-l- -(1,2,4-triazol- -l-yl)-2-but-2-yl]- -P-(2-carboxyethyl)- -P-methyl-phosphinate

Table 3 List of active ingredients used in synergistic combinations

o . Active ingredient Chemical name

1. Benomyl methyl l-(butylcarbamoyl)-2-benz- imidazolecarbamate

2. Benalaxyl DL-alanine-N-(2,6-dimethylpheny1)-

-N-(phenylacetyl)methylester 3. Blasticidin-S 1-(1 ^• -cytodinyl)-4-/L-3'-amino-5'-

-(l"-N-methyl-guanidino)-valeryl- mino/-l , 2 , 3 , 4-tetradeoxy-beta-D-

-erythro-hex-2-ene uronic acid

Buthiobate butyl 4-tert-butylbenzyl N- ( 3-pyridyl ) -

-dithiocarbonimidate

5. Cycloheximide 3-/2- ( 3 , 5-dimethyl-2-oxocyclohexyl ) -

-2-hydroxyethyl/-glutarimide

6. Cymoxanol 1- ( 2-cyano-2-methoxyiminoacetyl ) -3-

-ethylurea

7. Dinocap 2- ( l-methylheptyl ) -4 , 6-dinitrophenyl crotonate

8. Diethophencarb 3 ' , ' -diethoxyphenyl-isopropyl-carbamate

9. Dimethomorph (E , Z ) -4-/3- ( 4-chlorophenyl ) -3- ( 3 , 4-

-dimethoxyphenyl ) acryloyl/morpholine

10. Dodemorph 4-cyclododecyl-2 , 6-dimethyl-morpholine

11. Dodine 1-dodecylguanidine acetate

12. Ethridiasole 3-trichloromethyl-l, 2 , 4-thiadiazol-5-

-yl ethylether

13. Fenarimol a ( 2-chlorophenyl ) -a- ( 4-chloropheny 1 ) -

-5- (pyrimidinemethanol )

14. Fenpropimorph 4-/3-/4- ( l, 1-dimethyl ethyl )phenyl/-

-2-methylpropyl/-2 , 6- ( cis ) -dimethyl- morpholin

15. Fentine Acetate triphenyltin (IV) acetate 16. Fentine Hydroxide triphenyltin (IV) hydroxide

Table 3

(contd. )

No. Active ingredient Chemical name 17. Ferbam ferric dimethyl dithiocarbamate

18. Furazolidon 3-(5-nitrofurylidene amine)-2-oxazo- lidinone

19. Guazatin Acetate 9-aza-l,17-diguanidinoheptadecane triacetate 20. Hymexazol 3-hydroxy-5-methyl-isoxazole

21. Imazalyl 1-/2-(2, -dichlorophenyl)-2-(2-

-propenyloxy)ethyl/-lH-imidazole

22. Kasugamycin /5-amino-2-methyl-6-(2,3,4,5,6-

-pentahydroxy cyclohexyloxy)-

-tetrahydropyrane-3-yl)-amino-alpha-

-iminoacetic acid

23. Carbendazim 2-(methoxycarbonylamino)-benzimidazole

24. Carboxin 5,6-dihydro-2-methyl-N-phenyl-l,4-

-oxathiin-3-carboxamide

25. Maneb manganese ethylenebisdithiocarbamate

26. Metalaxyl N-(2,6-dimethylphenyl)-N-(methoxy- acetyl)-alanine methyl ester

27. Miclobutanyl 2-p-chlorophenyl-2-(1H-1,2, -triazolyl-

-l-ylmethyl)-hexane nitrile

28. Nystatin tetraene macrolide antibiotic

29. Ofurace 2-chloro-N-(2,6-dimethylphenyl)-N-

-tetrahydro-2-oxo-3-furanyl) acetamide

30. Oxadixyl 2-methoxy-N-(2-oxo-l,3-oxazolidine-3-

-yl)-acet-2' ,6'-xylidide

31. Pyrazophos 0,0-diethyl-0-(5-methyl-6-ethoxy-

-pyrazolo[ 1,5-a)pyrimid-2-yl)-

-thionophosphate

32. Polyoxines l-5'-N-(5"-0-carbomonyl-2"-amino-2"-

-deoxy-L-xylonyl)-5*-amino-5'-deoxy-

-beta-D-allofuranonyl-uronic acid)-

Table 3

(contd. )

No. Active ingredient Chemical name

5-hydroxymethyl uracil and the analogues thereof

33. Prochloraz 1-N-propyl-N-(2-(2, ,6-(trichloro- phenoxy)ethyl)carbamoyl) imidazole

34. Propiconazole (±)-1-(2-(2,4-dichlorophenyl)-4-

-propyl-1,3-dioxolane-2-ylmethyl)-

-1H-1,2,4-triazole

35. Streptomycine streptidine streptose-2-amino- methylglucose

36. Thira tetramethylthiurame disulfide

37. Thiabendazole 2-(thiazole-4-yl)-benzimidazole

38. Thiophanate-Methyl dimethyl /(1,2-phenylene)bis-(imino- carbonothioy1)/bis(carbamate)

39. Triadimefon 1-(4-chlorophenoxy)-3,3-dimethyl-l-

-(1H-1,2,4-triazol-l-yl)-2-butanone

40. Triadimenol beta-( -chlorphenoxy)-alρhy-1,1-di- methylethyl)-1H-1,2,4-triazole-l-

-ethanol

41. Triforin N,N'-(1,4-piperazinediyl-bis(2,2,2-

-trichloroethylidene)/-bis(formamide) 42. Tridemorph reaction mixture of C^-C^ 4-al yl-

-2,6-dimethylmorpholine homologues containing 60 to 70 % of 4-tridecyl isomers

43. Zineb zinc ethylenebis(dithiocarbamate)

44. Zira zinc bis(dimethyldithiocarbamate)

45. Mancozeb manganese ethylenebisdithiocarbamate

46. Copperoxyquinolate copper bis(quinoline-δ-oleate)

47. Aldimorph 2,6-dimethyl-4-tridecyl-morpholine and

2,5-dimethyl-4-tridecyl-morpholine

The efficacy of the compositions comprising a com¬ pound of formula (I) depending on the intended use was evaluated in the conventional way; the number of healthy plants which avoided any loss, damage, infection, disease or the weight of the crop or material or the measure of infection or the degree of infection (on the basis of the symptoms characterizing the disease) was measured.

In case of materials and products subjected to bio¬ deterioration, the maintenance of the use value was considered as a measure of efficacy.

When the efficacy of the compositions of the invention, comprising other known active ingredients in addition to the compounds of the general formula (I) was evaluated, the methods described in the following publications were followed:

COLBY, S.R. (1967) : Calculating synergistic and antagonistic responses of herbicide combinations (Weeds, 15: 20-22);

HORSFALL, J. G. & DIMMOND, A. E. (1941): Role of dosage-response curve in the evaluation of fungicides (Connecticut Experimental Station Bulletin 451: 635-667) ; SUN, Y. P. (1950) : Toxicity Index - an improved method of comparing the relative toxicity of insecticides (J. Econ. Entom. l: 45-53) ; BANKI, L. (1978) : Bioassay of pesticides in the laboratory (Academy Press, Budapest, Hungary) .

The invention is further illustrated by the following, non-limiting examples.

- 26 -

Example 1

Preparation of zinc dimethyldithiocarbamate

- dodecyl guanidiniu acetate

99 g (2.2 moles) of dimethyl-amine in form of 20 to 30 % by weight aqueous solution is added to a mixture of

88 g (2.2 moles) of sodium hydroxide and 750 ml of water.

To a flask supplied with a condenser, mechanical stirrer, thermometer and dropping funnel 175 g (2.3 moles) of carbon disulfide is added to the above solution under stirring and cooling, while keeping the temperature of the mixture below 25 °C, then stirring is continued until the amount of carbon disulfide forming the lower layer does not decrease any longer. Depending on the efficacy of the stirring, 1 to 1.5 hours are required. The excess of carbon disulfide (expected amount: 7.6 g) is separated and the aqueous phase is supplemented to 1260 ml with water. Thus 25 % by weight/volume of aqueous sodium dimethyldithiocarbamate solution is obtained.

A product of technical purity, comprising 287 g (1 mole) of dodecyl guanidine acetate is added to a solution of 288 g (1 mole) of zinc sulfate heptahydrate and 7 litres of water. The mixture is heated to 80 °C under constant heating and stirring than stirring is continued for 15 minutes while keeping the temperature at 80 to 85 °C. The dodecyl guanidinium acetate - zinc sulfate complex precipitates in the form of a hydrophobic product from the reaction mixture.

The mixture is cooled to a temperature of 20 °C by ceasing hte heating or by cooling, then the sodium dimethyldithiocarbamate solution, prepared as described hereinabove, is added under constant stirring at a tem¬ perature below 25 °C and the stirring is continued for 3 hours.

The precipitated solid substance is separated, washed with water until the washing lye does not comprise

any inorganic salt, then the product is dried at a tem¬ perature not exceeding 65 °C.

Thus 562-591 g (95-100 %) of white, solid, hydro- phobic product is obtained. Melting point: 196-252 °C (crude product)

253-256 °C (after recrystallization from toluene) Elementar analysis:

Calculated: N: 11.86 %; S: 21.69 %; Found: N: 11.89 %; S: 20.74 %.

The product does not comprise dodecyl guanidinium acetate according to thin-layer chromatographic analysis.

Example 2 Preparation of copper(II)-dimethyl-dithiocarbamate- -dodecyl guanidinium lactate

To 4.55 g (0.025 mole) of copper(II) acetate dis¬ solved in 150 ml of water 7.2 g (0.025 mole) of dodecyl guanidinium acetate are added, then the mixture is heated for 30 minutes at a temperature of 50 to 55 °C. The initially clear, blue solution turns to green and turbid. The mixture is cooled to a temperature of 20 °C, and 35 ml from the 25 % sodium dimethyldithiocarbamate solution, prepared according to Example 1, are added. The bvrown, turbid mixture is thoroughly stirred for 3 hours, then the product is worked up as described in Example 1. Elementar analysis: Calculated: N: 11.39 %; Found: N: 11.84 %. The product does not comprise dodecyl guanidinium acetate according to thin-layer chromatographic analysis.

Example 3

Preparation of zinc-dimethyl dithiocarbamate - dodecyl guanidinium lactate

7.9 g (0.1 mole) of zinc oxide is dissolved in a mixture of 27 g (0.3 mole) of lactic acid and 200 ml of water. Then 22.7 g (0.1 mole) of dodecyl guanidine is added to the solution and the mixture is stirred at a temperature of 85 to 90 °C for 30 minutes. After cooling 120 ml (0.21 mole) of sodium dimethyldithiocarbamate solution, prepared according to Example 1, is added at a temperature below 25 °C and the mixture is thoroughly stirred for 4 hours. Thus 53.3 g (86 %) of pale yellow, solid product is obtained.

Elementar analysis: Calculated: N: 11.23 %; Found: N: 11.31 %. The product does not comprise dodecyl guanidinium acetate according to thin-layer chromatographic analysis.

Example 4

Preparation of zinc-dimethyl-dithiocarbamate - dodecyl guanidinium 2-methylbenzoate

A mixture of 4.1 g (0.03 mole) of 2-methyl benzoic acid, 6.8 g (0.03 mole) of dodecyl guanidine and 100 ml of water are thoroughly stirred at a temperature of 85 °C for 10 minutes. Then a solution of 8.6 g (0.03 mole) of zinc sulfate heptahydrate and 30 ml of water are added to the bilayer mixture, and the stirring is continued for 45 minutes while the temperature of the mixture is kept at 80 to 85 °C. 38 ml (0.066 mole) of sodium dimethyl¬ dithiocarbamate solution, prepared according to Example 1, is added and the mixture is stirred at a temperature of 80 to 85 °C for 30 minutes, then it is left to cool while the stirring is maintained.

The product is worked up as described in Example 1, thus 16.65 g (87 %) of ochreyellow, solid product are obtained.

- 29 -

Elementar analysis: Calculated: N: 10.46 %; Found: N: 10.41 %.

The product does not comprise dodecyl guanidinium acetate according to thin-layer chromatographic analysis.

Example 5

Preparation of zinc-dimrethyl dithiocarbamate - dodecyl guanidinium dimethyldithiocarbamate To 28.7 g (0.1 mole) of dodecyl guanidine dissolved in 400 ml of water 183 ml (0.32 mole) of sodium dimethyldithiocarbamate solution, prepared according to Example 1, is added and the mixture is stirred at a temperature of 65 to 70 °C for 20 minutes. Then 28.8 g (0.1 mole) of zinc sulfate heptahydrate dissolved in 150 ml of water is added to the bilayer reaction mixture, then the mixture is thoroughly stirred at a temperature of 75 to 80 °C for 30 minutes.

After cooling, the product is worked up as described in Example 1. Thus 60 g (92 %) of white, solid product is obtained. Elementar analysis: Calculated: N: 12.9 %; Found: N: 13.5 %. The product does not comprise dodecyl guanidinium acetate according to thin-layer chromatographic analysis.

Example 6

Active ingredient(s) 32.5 % by weight Cyclohexanone 40.0 % by weight t-Butanol 10.0 % by weight

Oil 4.0 % by weight

Polyethylene glycol 6000 10.0 % by weight Polyoxyethylene anhydrosorbitol monolaurate 1.0 % by weight

Polyoxyethylene anhydrosorbitol 0.5 % by weight monopaImitate

Octylphenyl-polyglycolether 0.5 % by weight

(Triton X-100)

Nonionic surfactant (Atlox 3300B) 0.2 % by weight

Fatty alcohol-polyglycolether 0.3 % by weight

(Genapol 2)

Fatty alcohol-polyglycolether 1.0 % by weight

(Emulsogen 1-40)

Example 7

Active ingredient(s) 50.0 % by weight

Water 30.0 % by weight

Ethylene glycol 5.0 % by weight Cyclohexanone 4.0 % by weight

Polyethylene glycol 20000 4.0 % by weight

Cyclodextrin 1.0 % by weight

Emulsifying agent 6.0 % by weight

Example 8

Active ingredient(s) 75.0 % by weight

Beta-cyclodextrin 5.0 % by weight

Dextran 11.0 % by weight

Polyoxyethylene anhydrosorbitol 2.0 % by weight monolaurate

Polyoxyethylene anhydrosorbitol 1.0 % by weight monooleate

Octylphenyl-polyglycolether 1.0 % by weight

Potassium lignine sulfonate 5.0 % by weight

Example 9

Active ingredient(s) 25.0 % by weight

Polyethylene glycol 20000 30.0 % by weight

Dextran 16.0 % by weight Diato aceous earth 25.0 % by weight

Polyoxyethylene anhydrosorbitol 2.0 % by weight monolaurate

Fatty alcohol polyglycol ether 1.0 % by weight

Octylphenyl-polyglycol ether 1.0 % by weight Example 10

Active ingredient(s) 0.3 % by weight

Beta-cyclodextrine 0.6 % by weight

Dextran 1.3 % by weight

Diluent: 97.0 % by weight at least 40 % by weight of natural fibrous material (stem, sawdust, extraction residue, fiber, chaff, seed-vessel) Nutrient salt mixture 0.4 % by weight

Biodegradable binder (sticker of 0.4 % by weight vegetable or animal origin)

III. Biological tests Example 11

The antifungal activity of metal complexes of mixed ligand complexes

The suitably prepared suspension of the compounds was mixed to the nutrient medium composed of potato- dextrose agar just before laying the plate. The posioned plates were inoculated with mycelial discs of 3 to 5 mm diameter, out from the edge of 6 day old cultures, then the diameter of the grown colonies was measured after 72 hours. The inhibiting effect (inhibition %) of certain doses of each compounds of the growth of mycelia was calculated by comparing the diameters of the colonies grown on the nutrient discs free of antifungal compounds with those of the colonies grown on nutrient discs comprising the antifungal compounds.

The ED5 ₀ values were defined graphically on a log/probit paper by using the inhibition data and were expressed in μm/L.

The efficacy and the scope of activity of the com¬ pounds against hypomycetes are shown by Table 4.

Table 4 Result Fungus variety Host-plant Compounds

No. A B 11 1. Alternaria solani ^a potatoe 89 37 428 686

2. Ascochyta pisi ^a pea 506 484 1283 1390

3. Botryodiplodia theobromae ^a coconut 251 279 668 2665

4. Botrytis allii ^a onion 138 228 1383 888

5. Cladosporium cucumerinum ^d cucumber 138 83 347 207 6. Colletotrichum atramentarium^ pumpkin 394 30 1730 6240

7. Colletotrichum lindemuthuanum ^d bean 138 37 1349 9318

8. Colletotrichum dematium ^d soya bean 22 20 94 4182

9. Diaporthe helianthi* sunflower 20 20 387 13

10. Didymella applanata ³ raspberry 108 113 287 53 11. Drechslera teres ^a wheat 239 460 574 3597

12. Fusarium graminearum ^a wheat 51 653 234 2410

13. Fusariu oxysporum* tomato 62 169 261 440

14. Helminthosporium carbonum ³ maize 79 279 367 325

15. Macrophomina phaseollina^ sunflower 46 39 194 343 16. Mucor racemosus ² saprophyte 341 591 4255 1196

17. Nectria cinnabarina ^a currant 44 93 180 655

18. Nigrospora oryzae ^a maize 25 17 127 888

19. Penicillium sp. ^d grape 307 7288 1283 11381

20. Phoma betae ^a sugar beet 93 146 247 440 21. Phytophthora parasitica ⁰ polyphag 216 311 1490 932

22. Piricularia oryzae ^d rice 42 240 1349 2533

23. Rhizoctonia solani* ⁵ potato 560 535 701 2801

24. Rhizopus nigricans ² paprika 34 146 154 981

25. Thielaviopsis basicola ^a tobacco 138 108 448 163 26. Trametes versicolor" apricot 56 59 1233 163

Explanation of the abbreviations of Table 4; A = DMDTCZnDA (formulated according to Example 8) B = DMDTCCuDA (formulated according to Example 8) = NaDMDTC = sodium dimethyldithiocarbamate 11 = dodine (commercially available composition ° = Oomycetes ^a = Ascomycetes b = Basidiomycetes ^d = Deuteromycetes ^z = Zygomycetes

Example 12

Antibacterial effect of mixed ligand metal complexes

To the micronised aqueous suspensions of the compounds (0.2 ml) 0.1 ml of detergent solution (10 ml of TWEEN-20 dissolved in 1 ml of ethanol) is added, then the suspension is mixed to the appropriately prepared nutrient agar just before laying the plate.

The bacteria were inoculated to the poisoned nutrient plates with the aid of a multi-point inoculator, then the inhibiting effect (yes or no response compared to the untreated control) was evaluated after 48 hour incubation.

The effect was characterizhed by concentration (mg/litre) ranges, at the lower value of which the weak growth of bacteria can be observed, while at the upper value the inoculum used for inoculation is already killed.

(The above method is described in details by the publication of OROS, Gy. , CSERHATI, T. & SZOGYI, M. (1986): Acta Microbiologica Hungarica 33(2): 117-123).

The results are summarized in Tables 5 and 6.

Table 5

Compounds

No. Name of bacteria code βl B 11 CuSO

1. A. radiobacter ^x K84 25-50 6-13 25-50 /250 13-25 /100

2. B. thϋringiensis ^x 6-13 6-13 6-13 13-25 6-13 /100

3. Br . japonicum B-38 6-13 13-25 25-50 /250 13-25 /100

4. E. herbicola ^x D-5 25-50 25-50 25-50 50-100 50-100 /100

5. E. uredovora Vfr3 25-50 6-13 25-50 /250 25-50 /100

6. P. fluorescens ^x K-20 /100 50-100 /250 /100 /100 /ιoo

7. C. betae 6 3-6 6-13 6-13 50-100 13-25 /ιoo

8. C. flacciumfaciens 8 6-13 6-13 6-13 50-100 13-25 /ιoo

9. C. michiganense 9 3-6 6-13 6-13 50-100 13-25 /ιoo

10. C. cortii 11 12-25 6-13 6-13 50-100 25-50 /100

11. E. chrysanthemi B-25 25-50 13-25 3-6 13-25 25-50 /ιoo

12. X. alfalfae 26 6-13 6-13 6-13 50-100 6-13 /ιoo

13. X. campestris 27 13-25 6-13 6-13 25-50 13-25 /ιoo

14. X. malvacearum 36 13-25 3-6 3-6 13-25 6-13 /ιoo

15. X. phaseoli 33 3-6 3-6 3-6 25-50 6-13 /ιoo

16. X. stewartii 40 13-25 13-25 13-25 25-50 /100 /100

17. X. vesicatoria 29 13-25 6-13 6-13 25-50 13-25 /ιoo

Table 6

Compounds

No. Name of bacteria code 44 11 36 ZnSθ ₄

1. A. radiobacter ^x K84 25-50 6-13 25-50 /250 13-25 /100

2. A. tumefaciens 0 13-25 6-13 25-50 125-250 13-25 /100

3. A. tumefaciens 0-54 3-6 6-13 25-50 50-100 13-25 /100

4. A. tumefaciens B-6 13-25 6-13 25-50 125-250 13-25 /100

5. Br. japonicum B-38 6-13 13-25 25-50 /250 13-25 /100 6. E. herbicola ^x D-5 25-50 25-50 25-50 50-100 50-100 /lOO

Table 6 ( contd. )

Compounds No. Name of bacteria code 44 11 36 ZnS0 ₄

7. E. atroseptica 25-50 6-13 25-50 125-250 25-50 /100

8. E. carotovora 25-50 6-13 25-50 125-250 25-50 /100

9. E. chrysantemi B-25 25-50 13-25 3-6 13-2E 25-50 /100 10. E. uredovora ^x Vfr3 25-50 6-13 25-50 /250 25-50 /100

11. P. fluorescens ^x K-20 /100 50-100 /250 /100 /100 /100

12. P. syringae 12 25-50 13-25 25-50 /250 50-100 /100

13. P. syringae 13 50-100 6-13 25-50 /250 25-50 /100

14. P. syringae 18 50-100 6-13 25-50 /250 25-50 /100 15. X. alfalfae 26 6-13 6-13 6-13 50-10C 6-13 /100

16. X. campestris 27 13-25 6-13 6-13 25-50 13-25 /100

17. X. malvacearum 36 13-25 3-6 3-6 13-25 6-13 /100

18. X. phaseoli 33 3-6 3-6 3-6 25-50 6-13 /100

19. X. stewartii 40 13-25 13-25 13-25 25-5C /100 /100 20. X. vesicatoria 29 13-25 6-13 6-13 25-5C 13-25 /ιoo

21. B. subtilis ^x B-15 3-6 6-13 1-3 13-25 1-3 /ιoo

22. B. thϋringiensis ^x 6-13 6-13 6-13 13-2Ξ 6-13 /100

23. B. betae 6 3-6 6-13 6-13 50-10C 13-25 /ιoo

24. C. fascians 7 6-13 6-13 13-25 50-10C 13-25 /ιoo 25. C. flaccumfaciens 8 6-13 6-13 6-13 50-10C 13-25 /100

26. C. michiganense 9 3-6 6-13 6-13 50-lOC 13-25 /100

27. C. cortii 11 12-25 6-13 6-13 50-10: 25-50 /100

Explanation of the abbreviations of Table 6. A = DMDTCZnDA 11 = Dodine 36 = Thiram 44 = Ziram = NaDMDTC

x = Sapriphytonic or symbionic species antagonist against pathogenic microorganisms $_ — Agrobacterium B = Bacillus Br = Bradyrhizobium C = Cornyebacterium E = Erwinia P = Pseudomonas X = Xantho onas

Example 13

Test of oomyceta-killing activity

Aliquot portions of the suitably prepared suspension of the test compounds are added to the appropriately prepared liquid, intended for dressing sun¬ flower (Helianthus annuus L. ; Compositae, Asterales) seeds, just before the immersion of the seeds into the liquid.

The treated seeds are left to stand for 24 hours, then seeded into sterile soil and grown in a glasshouse.

The mildew (Plasmopara haalstedii (Farl.)) infec¬ tion is evaluated in comparision with the untreated control and the efficacy of the treatment is calculated.

100 = complete control 0 = no effect

The test is described in details in the publication OROS & VIRANYI (1987): Ann. Appl. Biol., 110:53-63.

Results of Example 13

T R E A T M E N T S Inhibiting effect (%) Formulation

No. Compound dose A ^a growth (%) ^b

1. A (DMDTCZnDA) 50 30 57 2. B (DMDTCCuDA) 50 55 57

Results of Example 13

T R E A T M E N T S Inhibiting effect (%) Formulation

No. Compound dose growth (%) ^b

3. Benalaxyl (2) 50 ^c 95 comm.av.

4. Cymoxanyl (6) 50 ^c 90 comm.av.

5. Ofurace (29) 50 ^c 97 6

6. Oxadixyl (30) 50 ^c 99 comm.av.

7. Ziram (44) 50 ^c 30 57

8. Cu-DMDTC (1) 50 10 57

9. Dodine (11) 50 15

10. Na-DMDTC ( ) 50 10

11. ZnS0 ₄ 50 35

12. CuSθ ₄ 50 25

13. A + B (1:1) 50 45 57

14. A + 2 (1:4) 50 100 + 5 % 57

15. A + 6 (1:4) 50 100 +10 % 57

16. A + 29 (2:3) 50 100 + 3 % 57

17. A + 30 (2:3) 50 100 + 1 % 57

18. B + 2 (1:4) 50 100 + 5 % 57

19. B + 6 (1:4) 50 100 +10 % 57

20. B + 29 (2:3) 50 100 + 3 % 57

21 B + 30 (2:3) 50 100 + 1 % 57

22. A + 2 + 6 (3:1:1) 50 100 + 5 % 57

23. A + 29+ 6 (2:2:1) 50 100 + 3 % 57

24. A + 30+ 6 (2:2:1) 50 100 + 1 % 57

26. B + 29+ 6 (2:2:1) 50 100 + 3 % 57

27. B + 30+ 6 (2:2:1) 50 100 + 1 % 57

28. Thiram (36) 50 ^c 40 comm.av.

30. Zineb (43) ^d 50 ^c 25 57 ^a = inhibition of sporulation ^b = according to the method of HORSFALL & DIMMOND ^c = state of the art d = mutagenic comm. av. = commercially available

Example 14

Control of apple scab

One of the most significant pathogens jeopardizing the foliage and crop of po iferous trees in Venturia inaequalis Pers. (Dothideales, Ascomycetes) , which is able to infect the hostplant at any period of vegetation. Considering that the fruits infected at an early stage of raping become unattractive, thus they become commercially unvaluable, moreover, the storability of the fruits infected at a later period of vegetation is reduced by the disease, the pomiferous trees have to be protected from sprouting to the possible latest time determined by sanitary points of view.

As the pathogenic fungus continuously produces infectious conidia from early spring to the end of vegetation and the apple tree is an intensively growing plant, the damage is prevented by frequent spraying. The pathogenic fungis is continuously subjected to the selection pressure of the fungicide due to the frequently repeated treatments, therefore, according to experience, the efficacy of the applied compositions is rapidly reduced cdue to the increase of the number of strains resistant against the active ingredient appearing in the population of the pathogen. As a result of the loss of efficacy, the application of more, formerly widely used compositions (benomyl, dodine) had to be given us (OROS, 1981) .

The efficacy of the compositions comprising a com¬ pound of the general formula (I) as single active ingredient or a combination of a compound of the general formula (I) according to the invention, and benomyl was compared to that of other compositions (Rubigan 12 ec, Eli Lilly, active ingredient: triadimefon) widely used in the present agricultural practice under field condition. The tests were carried out on apple trees "Golden

Delicious" in a plot of 1/8 ha.

The dose of the composition was 75 g of active ingredient/100 1 of spray.

100-100 leaves and 100-100 fruits on 10-10 apple trees were examined in each plots when evaluating the efficacy of the treatments. The results was expressed in the % of infection and the efficacy of the treatment was calculated as follows:

(100-a) - (100-K)

Efficacy = 100 x

K wherein K = infection of the untreated controls, A = infection of the treated trees.

The character of the interaction was defined according to the method of HORSFALL and DIMMOND.

Results of the tests according to Example 14

Condition of the foliage:

Treatment Contamination Efficacy No. Active ingredient dose % %

1. Non-treated 0 65.8

2. Operative 14 x 75 g 30.1 54.2 treatment ⁹

3. Operative 6 x 75 g treatment

A (DMDTCZnDA) 2 x 75 g

Operative 1 x 75 g treatment

A (DMDTCZnDA) 2 x 75 g

OOppeerraattiivvee 33 xx 7755 gσ 1199..55 69.9+15.7% ^b treatment

Results of the tests according to Example 14

(contd.)

Condition of the foliage:

Treatment Contamination Efficacy

No. Active ingredient dose % %

4. Operative 6 x 75 g treatment A (DMDTCZnDA)

+benomyl (1) (7:3) 2 x 75 g Operative 1 x 75 g treatment A (DMDTCZnDA) +benomyl (1) (7:3) 2 x 75 g

Operative 3 x 75 g 11.5 82.5+13.6% ^c treatment

^a = 13+39 = tank mixture of Rubigan 12 ec+Bayleton 25 wp (1:1 w/w phenarimol and triadimephon calculated for the active ingredient) *> = compared to treatment 2 ^c = compared to treatment 3.

Results of the tests according to Example 14

Condition of the fruits

Treatment Contamination Efficacy No. Active ingredient dose % %

1. Non-treated 0 22.0

2. Operative 14 x 75 g 7.5 65.9 treatment ³

3. Operative 6 x 75 g treatment

Results of the tests according to Example 14

(contd. )

Condition of the fruits

Treatment Contamination Efficacy

No. Active ingredient dose % %

A (DMDTCZnDA) 2 X 75 g

Operative 1 X 75 g treatment

A (DMDTCZnDA) 2 X 75 g

3 X 75 g 7.5 65.9

4. Operative 6 X 75 g treatment A (DMDTCZnDA)

+benomyl (1) (7:3) 2 X 75 g

Operative 1 X 75 g treatment

A (DMDTCZnDA)

+benomyl (1) (7:3) 2 X 75 g

Operative 3 X 75 g 6.0 72. .7+ 6.8% ^b treatment

^a = 13+39 = tank mixture of Rubigan 12 ec+Bayleton 25 wp (1:1 w/w phenarimol and triadimephon calculated for the active ingredient) ° = compared to treatment 3.

Example IS Test of the antifungal activity on onion under field conditions

Among the pathogens jeopardizing the roots and bulbs of bulb crops (e.g. Allium species; Monocotyle- dones) the Fusarium species, such as F. oxysporum (Deuteromycetes) , F. solani (Ascomycetes) belong to the

most important ones as they are able to infect the host plant at any period of vegetation. Considering that th infection may kill the plants infected at an early stag of vegetation, the fact that the storability of the onions infected at a later stage of vegetation is reduce by the disease, and with reagrd to hygienic aspects th onion has to be protected from the beginning of seedin or planting until the possibly latest time.

As onion is a vegetable and the plant part to be protected, i.e. exposed to pesticidal effect, is directl consumed frequently without cooking, due to huma sanitary points of view such compositions can be applie which are quickly decomposed or do not produce any toxi methabolite. The application of a certain composition has to b given up when the number of strains resistant agains the highly selective active ingredient of the composition, appearing in the population of F. oxysporum, parasiting the onion used for eating (A. cepa L. ; Liliales, Monocotiledones) , is increased as the composi¬ tion may loose its efficacy.

In order to prevent the said phenomenon, the simultaneous application of active ingredients of different mode of action is proposed. This is supported by the fact that the scope of activity of highly selective (therefore considered as environment- and health compatible) active ingredients is too narrow, therefore there is an increased hazard that the onion will be infected through the soil by pathogens which can be classified into very different taxonomic categories (e.g. F. oxysporum and Botrytis species) after planting.

The disadvantage of zineb and maneb (dithio¬ carbamate metal complexes) , widely used in onion together with the selective fungicidal agents, is that a highly poisonous methabolite (ETU) is formed in the treated

plants during the decomposition of the antifungal com¬ pounds. Therefore these compounds can be applied onto the plants during a certain period of vegetation only. Thus the otherwise excellent antifungal activity thereof cannot completely be utilized by the farmer.

The efficacy of the compositions according to the invention was compared to that of the antifungal mixture presently proposed to be used in agricultural practice in a soil infecting test. The onion was "Bronze of Makό" and it was infected with Aspergillus niger. Penicillium spp., Fusarium spp., Botrytis spp., Pseudo onas spp., and Peronospora destructor pathogens. The frequency of occurrance of the pathogens was reduced in the order of their listing. The size of the plot was 2 m ² . The soil was infected by incorporating 25 pieces of onion, infected with Fusarium species in the previous vegetation period, into 1 m ² of soil. F. oxysporum. F. solani and F. culmorum species could be breeded in the onions used for infection. The dose of the compositions according to the invention was active ingredient calculated for 1 metric ton of anion. As control, 1 metric ton of onion was treated with 3 kg of composition (1 kg of Agrocite (1), + 1 kg of Dithan M 45 (45) + 1 kg of Quinolat V-4x (26+46)). The efficacy of the treatments was evaluated by assessing the pathological condition of 100-100 onion plants 6 weeks after planting.

The result was expressed in the % of the infection, and the efficacy of the treatment was calculated according to the formula:

- K«

Efficacy = 100 x

100 - K _e wherein K _e = the number of the healthy plants in the control plot

A _e = the number of the healthy plants in the treated plot. The character of the interaction was evaluated on the basis of the method of HORSFALL and DIMMOND. Results of the test according to Example 15 Treatment Without infection Efficacy

No. Active ingredient dose ^a % %

1. Non-treated 0 22 2. Operative treatment* ³ 1950 61 50

3. A (DMDTCZnDA) 850 58 46

4. Benomyl (1) 850 34 15

5. Micobutanyl (27) 850 46 31

6. Benomyl (1) + A (4:11) 850 64 54 + 4 % ^c

7. Micobutanyl (27)

+ A (4:11) 850 56 43 - 2 %

8. Micobutanyl (27)

+ Benomyl (1) (1:1) 850 ^α 53 40 + 9 % 9. Micobutanyl (27) + Benomyl (1)

+ A (4:4:11) 850 92 90 + 44 % ^a = g of active ingredient calculated for 1 t of seed onion (wet dressing) ^b = in the aghricultural metric ton of seed onion is treated with a tank mixture comprising 500 g of benomyl (1), 500 g of carboxine (24), 800 g of mancoseb (45) and 150 g of copper oxyquinolate (46) ^c = the improvement of efficacy was compared to the most effective fungicidal agent being the component of the mixture. The following formulations were used: A = Example 8 1 = Benlate 50 wp

27 = Systhane 12.5 ec A+l, A+27, A+l+27 = Example 9

Example 16

Control of powdery mildew on wheat

Wheat (Trit-icum sp. ; Graminaceae, Poales, Mono- cotyledones) plants were sprayed with the suitably pre¬ pared solution of the compounds (the concentration is mg of active ingredient calculated for 1 litre of spray 1 day after the infection.

8 days later the powdery mildew (Erysiphe graminis; Erysiphales, Ascomycetes) colonies, situated on each leaves were counted. The efficacy of the treatments was calculated on the basis of the reduction of the number of the colonies on the treated leaves compared to that on the untreated control and expressed in %.

Results of Example 16

T R E A T M E N T Formulation Efficacy (%)

No. Compound dose Inhibi Growth of tion inhibition

1. ZnS0 ₄ 200 18 - 2. Na-DMDTC ( ) 200 39 - 3. Dodine (11) (base) ³ 200 8 46 - 4. Dodine Acetate (11) 200 7 26 - 5. Ziram (44) 200 8 26 - 6. Zineb (43) ^b 200 comm. av. 56 - 7. Zn-acetate 200 9 49 - 8. A (DMDTCZnDA) 200 9 67 + 18 % 9. Zn-dimethyldithio- 200 9 28 - carbamate-dodecyl- guanidine complex

10. 44 + 11 (1:1) 200 31

^a = phytotoxic; ^b = mutagenic; ^c = compared to treatment 7,