WO1985004333A1

WO1985004333A1 - A biocidal, particularly fungicidal and/or bactericidal, composition

Info

Publication number: WO1985004333A1
Application number: PCT/DK1985/000028
Authority: WO
Inventors: Anita Wenger; Hans Kolind-Andersen; Niels Jacobsen
Original assignee: A/S Cheminova
Priority date: 1984-03-23
Filing date: 1985-03-20
Publication date: 1985-10-10
Also published as: ZA851904B; EP0175725A1; DK165284A; AU4152585A; DK165284D0

Abstract

A biocidal composition, particularly a fungicidal and/or bactericidal composition, comprising a thiosemicarbazide, a thionocarbazate or a dithiocarbazate which, when using the composition, exhibits hitherto unknown biocidal properties. The thiosemicarbazide, thionocarbazate or dithiocarbazate contained in the composition belongs to the group of compounds having the general formula (I), and their complexes formed by reaction with compounds of the metals, Cu, Zn, Mn, Fe, Ca, Mg, Al, Sn and Ti having inorganic and/or organic ligands, and salts of said compounds. The compounds of the invention and particularly their metal complexes exhibit surprising fungicidal and bactericidal activities. They may particularly be used for combating or preventing attacks by fungi or bacteria or plants on plant material, including seed material.

Description

A biocidal, particularly fungicidal and/or bactericidal, composition.

The present invention relates to a biocidal, particularly fungicidal and/or bactericidal composition comprising a thiosemicarbazide, a thionocarbazate or a dithiocarbazate, respectively, or a metal complex of said three types of compounds, which, when using the composition, exhibits hitherto unknown biocidal properties. The invention also relates to thiosemicarbazides, thionocarbazates and dithiocarbazates and metal complexes thereof, and salts thereof, for use in the composition. Furthermore, the invention relates to a method for combating or preventing attacks by phytopa- thogenic organisms on plants or plant material.

The biocidal composition of the invention is characterized in that the thiosemicarbazides, thionocarbazates and dithiocarbazates. contained therein belong to the group of compounds having the general formula I

and their complexes formed by reaction with compounds of the metals Cu, Zn, Mn, Fe, Ca, Mg, Al, Sn and Ti having inorganic and/or organic ligands, and salts of said compounds, in which formula Y represents CH or N,

X₁ represents hydrogen, straight or branched chain alkyl having up to 6 carbon atoms, alkoxy having up to 6 carbon atoms, phenoxy or halogen, and n is 1, 2 or 3, or (X₁)_n when taken together form a fused benzene ring, R₁, R₂, R₃, R₄, R₅ and R₆ each independently represents hydrogen or straight or branched chain alkyl having up to 6 carbon atoms , and m is 0 , 1 , 2 or 3 , and

A represents or O-R₉, S-R₉ or R₉,

R₇ and R₈ each independently represents hydrogen, straight and branched chain alkyl or alkylen having up to 18 carbon atoms, cycloalkyl, arylalkyl, heteroarylalkyl, aryl, substituted aryl, a heterocyclic ring containing one or more hetero atoms, acyl, hydroxy or alkoxy, alkylsulphonyl or arylsulphonyl, amino, alkylamino or dialkylamino, arylamino, hydroxyalkyl or alkoxyalkyl, aminoalkyl, monoalkylaminoalkyl or dialkylaminoalkyl, alkoxycarbonylalkyl or alkylideneimino, or R₇ and R₈ when taken together with the nitrogen atom to which they are attached form a heterocyclic ring which may optionally contain one or more additional hetero atoms selected from O, N and S, and R₉ represents hydrogen, straight or branched chain alkyl or alkenyl having up to 18 carbon atoms, cycloalkyl, arylalkyl, heterόarylalkyl, aryl, substituted aryl, a heterocyclic ring containing one or more hetero atoms, haloalkyl, hydroxyalkyl or alkoxyalkyl, aminoalkyl, monoalkylaminoalkyl or dialkylaminoalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl or dialkylaminocarbonylalkyl, alkylcarbonylalky or arylcarbonylalkyl.

Examples of the ligands forming part of the metal complexes of the invention include neutral ligands such as H₂O, NH₃, amines and phosphines, anionic ligands such as the inorganic chlorides and sulphates and the organic alcoholates, phenolates, thiolates, carboxylates (including substituted carboxylates and amino acid anions),sulphonates and anions or organic CH acids, e.g. anions of β-dicarbonyl compounds.

It is known that tetra-alkylated thiosemicarbazides are effective fungicides and bactericides (see for example German published specification No. 1,926.768), that certain dithiobiuret metal complexes have fungicidal and plant growth regulating activities(see German published specification No. 2,120,723), and that pyridinyl thiosemicarbazides have antimalarial activity (see Daniel L. Klayman et al.. Journal of Medical Chemistry, 1984, Vol. 27, No. 1, page 87 et seq.).

It has surprisingly been found that the compounds of formula I and their metal complexes for practical requirements have a very favourable fungicidal and bactericidal activity for protecting cultivated plants. Cultivated plants are here, e.g., cereals, maize, rice, vegetables, sugar beets, soya, peanuts, fruit trees, ornamental plants, but above alle grape vines, hop, cucumber plants (cucumber, pumpkin, melon), solanaceae, such as potato, tobacco, and tomato, and also banana, cocoa, and natural caoutchouc plants.

Fungi occurring on plants or parts of plants (fruits, blossoms, flowers, foliage, stems, tubers, roots) can be inhibited or destroyed by the active compounds of the invention, whereby also plant parts growing up later on remain spared of such fungi.

The compounds of the invention are active against phytopathogenic fungi belonging to the following classes: Ascomycetes, Basidiomycetes such as rust fungi, Fungi imperfecti, e.g., Fusarium oxysporum and Botrytis cinerea, but particularly against the Oomycetes belonging to the class of Phycomycetes, such as Pythium sp., Phytophthora sp., Peronospora sp., Pseudoperonospora sp., and Plasmopara sp.

Furthermore, the compounds of the invention can be used for treating seed material (fruits, tubers, seed corn) and cuttings to protect them against fungal infections and against phytopathogenic fungi occurring in the soil.

The compounds of the invention are active against rot fungi belonging to the class of basidiomycetes. The compounds of the invention are bactericides which have shown activity against, e.g. Pseudomonas mors prunorum.

In accordance with the above the invention relates specifically to a biocidal composition as defined above intended for combating or preventing attacks by fungi or bacteria on plants or plant material, including seed material.

A particularly advantageous composition of this type is intended for combating or preventing attacks by oomycetes.

The invention also relates to thiosemicarbazides, thionocarbazates and dithiocarbazates of the general formula I and metal complexes thereof, or salts thereof, as defined above, for use in the compositions defined above.

Furthermore the invention relates to a method for combating or preventing attacks by fungi or bacteria on plants or plant material, including seed material, which method is characterized by treating the plants or plant material with an active amount of a thiosemicarbazide og thionocarbazate or dithiocarbazate of the general formula I or a metal complex thereof, or a salt thereof, as defined above. Among the compounds of formula I and their metal complexes mention should particularly be made of those described in the Tables 1 to 4 and in the Test Examples.

Preparation of thiosemicarbazides, thionocarbazates and dithiocarbazates.

The compounds of the general formula I as stated in Tables 1 and 2 below are prepared by one of the methods known in principle from the literature (ref. 1: Klayman et al., J. Med. Chem. 2£, 35-39 (1983)), viz. by reducing the corresponding thiosemicarbazone or the corresponding hydrazone-N-dithiocarboxylic acid ester or hydrazone-N-thionocarboxylic acid ester, respectively, with NaBH₄ (Method A), or by reacting methyl 3-[1-(2- pyridyl)ethyl] dithiocarbazate (21) or methyl 3-(2-pyridylmethyl)dithiocarbazate (22) with the respective amines (Method B). Two detailed Examples on the use of the general preparation methods are give below:

Example 1 (Method A)

4 ,4-Tetramethylene-1-(3-pyridyl)ethylthiosemicarbazide (compound No. 8)

A slurry of 3-acetylpyridine 4,4-tetramethylenethiosemicarbazone (8.7 g, 0.035 mole) in 70 ml of abs. alcohol is treated with NaBH. (1.6 g, 0.042 mole) at room temperature while stirring. The stirring is continued for about 20 hours, then 30 ml of water is added and the mixture neutralized with 3.5 ml of CH₃COOH. Thereupon crystals precipitate which are filtered off, rinsed with water and dried. Yield 7.4 g.

85%. M.p. 189-191ºC.

Example 2 (Method B)

4 , 4-Diethyl-1-(2-pyridyl)ethylthiosemicarbazide (compound No. 3) Methyl 3-[1-(2-pyridyl)ethyl]dithiocarbazate

(21) (13.6 g, 0.06 mole) and diethylamine (9.5 g, 0.13 mole) are refluxed in 100 ml of methanol for about 10 hours with liberation of CH₃SH. On cooling starting material (0.6 g, 0.0026 mol, 4.4%) is filtered off, and evaporation of the filtrate gives 14.1 g of crystalline product (0.056 mole, 93% yield). Recrystallization from 50 ml of aqueous methanol gives 7.3 g of crystalline product, m.p. 106-108ºC. Preparation of complexes of thiosemicarbazides and thiono- or dithiocarbazates, respectively.

Complexes of the compounds of the invention are prepared by reacting the latter with metal salts of inorganic or organic acids, optionally in the presence of neutral ligands.

The preparation takes place by dissolving the two starting materials - together or separately - usually at elevated temperature in suitable solvents such as water, methanol, ethanol, methylene chloride, acetonitrile or dimethylformamide (DMF) or combinations thereof. The temperature at which the starting materials have been combined is maintained for a shorter or longer time, whereupon the reaction mixture is filtered, if necessary, before cooling. On this cooling the product often crystallizes, but it may be necessary to add another solvent in order to promote this crystallization, or to evaporate the reaction mixture. Subsequently the products may be recrystallized from various solvents.

The compounds stated in Tables 3 and 4 below are prepared by mixing a hot methanolic or ethanolic solution of the corresponding substance from Table 1 or 2 with a hot methanolic or ethanolic solution of an equivalent quantity of cupric acetate while stirring. Immediately or on cooling a complex precipitates from the mixture which is filtered off and dried. If the complex does not precipitate directly, the reaction mixture is evaporated the acetic acid formed being azeotropically removed with toluene.

After this general preparation procedure two detailed Examples will now be given.

Example 3 (compound No. 102)

4 , 4-Dimethyl- (2-pyridyl) ethylthiosemicarbazide (compound No. 2) (1.1 g, 0.005 mole) is dissolved in 10 ml of hot MeOH and cupric acetate monohydrate (1.0 g, 0.005 mole) dissolved in 40 ml of hot MeOH plus a little HOAc is added thereto while stirring. The reaction mixture is evaporated and the last trace of HOAc is removed azeotropically with toluene. Thereby 1.9 g of blackish green crystals are isolated, m.p. 220 C (d) .

Example 4 (compound No. 121)

Methyl 3-[1-(2-pyridyl)ethyl]dithiocarbazate (21) (2.3 g, 0.01 mole) is dissolved in 10 ml of hot MeOH and cupric acetate monohydrate (2.0 g, 0.01 mole) dissolved in 90 ml of hot MeOH plus a little HOAc is added thereto while stirring. After stirring for a couple of hours at room temperature the reaction mixture is freezed, 2.1 g of blackish green crystals are filtered off, m.p. 165°C (d).

The compositions of the invention may be formulated as wettable powders, dusts, granules, solutions, emulsifiable concentrates, emulsions, suspension concentrates or aerosols. Wettable powders are usually formulated to contain 25, 50 or 75% of toxicant and usually contain, in addition to solid carrier, 3-10% by weight of a dispersing agent and, where necessary 0-10% by weight of stabilisers and/or additives such as penetrants or stickers.

Dusts are usually formulated as a dust concentrate having a similar composition to that of a wettable powder but without a dispersant and are diluted in the field with further solid carrier to give a composition usually containing 1/2-10% by weight of toxicant. Granules are usually prepared to have a size between 10 and 100 BS mesh, (1.676-0.152 mm) and may be manufactured by agglomeration or impregnation techniques. Generally, granules will contain 1/2-25% by weight toxicant and 0-10% by weight of additives such as stabilisers, slow release modifiers and binding agents. Emulsifiable concentrates usually contain, in addition to the solvent and, when necessary, co-solvent, 10-50% w/v toxicant, 2-20% w/v emulsifiers and 0-20% w/v of appropriate additives such as stabilisers, penetrants and corrosion inhibitors. Suspension concentrates are compounded so as to obtain a stable, non-sedimenting, flowable product and usually contain 10-75% by weight of toxicant, 1/2-15% by weight of dispersing agents, 0.1-10% by weight of suspending agents such as protective colloids and thixotropic agents, 0-10% by weight of appropriate additives such as defoamers, corrosion inhibitors, stabilisers, penetrants and stickers, and as carrier, water or an organic liquid in which the toxicant is substantially insoluble. Certain organic solids or inorganic salts may be dissolved in the carrier to assist in preventing sedimentation or as antifreeze agents for water. Aqueous dispersions and emulsions, for example, compositions obtained by diluting a wettable powder or a concentrate according to the invention with water, also lie within the scope of the present invention. The said emulsions may be of the water-in-oil or of the oil-in-water type, and may have a thick "mayon- naise"-like consistency.

The compositions may also contain other ingredients, for example, other compounds having pesticidal, particularly insecticidal, acaricidal, herbicidal or fungicidal properties.

The activities of the compounds of the invention are illustrated in detail by the following Test Examples.

Test Example 1

Agar plate test.

Testing for fungistatic activity and the breadth of the activity spectrum. Solvent: Ethanol.

Test concentration in ppm (mg substance per 1 agar):

200, 20, 2, 0.2.

The solution of activ substance in added to steril agar liquefied by heating, in such an amount that the desired concentration of active substance therein is obtained. After thorough shaking to uniform distribution of the active substance, the agar is poured into Petri dishes under sterile conditions.

After solidification of the mixture of substrate and active substance, test fungi from pure cultures are inoculated thereon in discs of a diameter of 5 mm.

The Petri dishes are left in 5 x 24 hours at 22°C for incubation.

After this period the inhibitory effect of the active substance on the mycelial growth is determined in categories in relation to untreated control dishes. + no mycelial growth

- mycelial growth, but inhibited in relation to control 0 mycelial growth like control

Active substances, concentrations of active substance, test fungi and inhibitory effect obtained appear from the Table below.

. t

Test Example 2

Seed dressing test.

Testing for protective activity against decay of bean seedlings caused by Pythium ultimum. Solvent: 10% acetone in water.

Emulsifier: Triton X-155 100 ppm.

Test concentrations in ppm (mg of substance per liter of solvent): 400, 200, 20 and 2. In dressing beans, they are immersed in a solution of active substance for one minute and airdried, 10 beans being immersed for each test concentration. The beans are incubated in closed Petri dishes, on moist filter paper inoculated with Pythium ultimum, for 6 x 24 hours at 22°C. Thereby the germination of the beans and the mycelial growth of Pythium ultimum are initiated. After this period of time the number of healthy seedlings are determined in relation to untreated, non-inoculated control dishes. The more active the active substance is, the more seedlings are healthy.

Active substances, concentrations of active substances in the dressing solution and the number of healthy seedlings in % appear from the Table below.

Test Example 3

Bacterial growth inhibition test.

Testing of bactericidal activity against Pseudomonas mors prunorum. Solvent: Ethanol.

Test concentrations in ppm (mg of substance per liter of solvent): 500, 250, 125.

Active substance is dissolved in ethanol in an amount such as to obtain the concentration required. Filter paper discs of 13 mm in diameter are immersed therein, air-dried and placed in Petri dishes (90 mm) with cooled solidified meat peptone agar inoculated on the surface with the test organism. The Petri dishes are incubated for 48 hours at 22°C.

After this period of time the inhibitory effect of the active substance is determined, the radius of the zone of inhibition being measured and recorded in % of the maximum inhibition which is obtained by using 250 ppm of chloramphenicol.

The results appear from the Table below.

Claims

Patent Claims

1. A biocidal composition, particularly a fungicidal and/or bactericidal composition, comprising a thiosemicarbazide, a thionocarbazate or a dithiocarbazate, respectively, or a metal complex of said three types of compounds, which, when using the composition, exhibits hitherto unknown biocidal properties, characterized in that said thiosemicarbazide, thionocarbazate and dithiocarbazate belong to the group of compounds having the general formula I

and their complexes formed by reaction with compounds of the metals, Cu, Zn, Mn, Fe, Ca, Mg, Al, Sn and Ti having inorganic and/or organic ligands, and salts of said compounds, in which formula Y represents CH or N,

X₁ represents hydrogen, straight or branched chain alkyl having up to 6 carbon atoms, alkoxy having up to 6 carbon atoms, phenoxy or halogen, and n is 1, 2 or 3, or (X₁)_n when taken together form a fused benzene ring,

R₁, R₂, R₃, R₄, R₅ and R₆ each independently represents hydrogen or straight or branched chain alkyl having up to 6 carbon atoms, and m is 0, 1, 2 or 3, and

A represents or O-R₉, S-R₉ or R₉ ,

R₇ and R₈ each independently represents hydrogen, straight or branched chain alkyl or alkenyl having up to 18 carbon atoms, cycloalkyl, arylalkyl, heteroarylalkyl, aryl, substituted aryl, a heterocyclic ring containing one or more hetero atoms, acyl, hydroxy or alkoxy, alkylsulphonyl or arylsulphonyl, amino, alkylamino or dialkylamino, arylamino, hydroxyalkyl or alkoxyalkyl, aminoalkyl, monoalkylaminoalkyl or dialkylaminoalkyl, alkoxycarbonylalkyl or alkylideneimino, or

R₇ and R₈ when taken together with the nitrogen atom to which they are attached form a heterocyclic ring which may optionally contain one or more additional hetero atoms selected from O, N and S, and R₉ represents hydrogen, straight or branched chain alkyl or alkenyl having up to 18 carbon atoms, cycloalkyl, arylalkyl, heteroarylalkyl, aryl, substituted aryl, a heterocyclic ring containing one or more hetero atoms, haloalkyl, hydroxyalkyl or alkoxyalkyl, aminoalkyl, monoalkylaminoalkyl or dialkylaminoalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl , monoalkylaminocarbonylalkyl or dialkylaminocarbonylalkyl, alkylcarbonylalkyl or arylcarbonylalkyl'.

2. A composition according to claim 1, intended for combating or preventing attacks by fungi or bacteria on plants or plant material, including seed material.

3. A composition according to claim 2, intended for combating or preventing attacks by oomycetes.

4. Thiosemicarbazides, thionocarbazates and dithiocarbazates and metal complexes thereof, and salts thereof, as defined in claim 1, for use in a composition as claimed in claim 1, 2 or 3.

5. A method for combating or preventing attacks by fungi or bacteria on plants or plant material, including seed material, characterized by treating the plants or plant material with an active amount of a thiosemicarbazide or thionocarbazate or dithiocarbazate, or a metal complex thereof, or a salt thereof, as defined in claim 1.