DE2020595B2 - l-Aryl-3- (2-chloraUyl> thioureas, process for their preparation and their use as microbicides - Google Patents

Description

RR ¹

in which R is hydrogen, chlorine, bromine, trifluoromethyl, nitro or C _{1 -C 4} ^{-alkyl and R 1 is} hydrogen, methyl or chlorine, as well as the bromine addition derivatives on the chloroallyl radical

2. l-Aryl-3- (2-chlorallyl) thioureas according to claim 1, in which the phenyl radical is substituted in the 3,4- or 3,5-position

3. l-Aryl-3- (2-chloraHyi) -thioureas according to claim 1 of the general formula

Cl

-C-NH-CH ₂ -C = CH ₂

5. 1 - (3,5-Di-trifluoromethylphenyl) -3- (2-chloroallyl) -thiourea the formula

S Cl

C NH CH2 C-CH2

6. 1 - (3,4-Dichlorophenyl) -3- (2-chloroallyl) thiourea of the formula

S Cl

Il I

-C-NH-CH ₂ -C = CH ₂

Cl

7. 1- (3,5-dichlorophenyl) -3- (2-chlorallyl) thiourea of the formula

S Cl

NH-C-NH-CH ₂ -C = CH ₂

& Process for the preparation of thioureas according to claim 1, characterized in that, in per se known manner either a Aryüsothiocyanat of the general formula Ar-N = C = S with 2-Chlorallylamin of formula

Cl
H ₂ N-CH ₂ -C = CH ₂

or an aniline of the general formula Ar-NH ₂ with 2-chloroallyl isothiocyanate of the formula

Cl
S = C = N-CH ₂ -C = CH ₂

reacts and optionally _{adds Cl 2} or Br _{2 to the} chlorallyl group

9. Microbiocidal agents containing at least one compound according to Claim 1.

Cl

NH-C-NH-CH ₂ -C = CH ₂

in which two of the substituents R, R 'and R "are identical or different and are Cl or CF ₃ , while the third is H.

4.1 - (3-Trifluoromethyl-4-chlorophenyl) -3- (2-chloroal-Iyl) -thiourea the formula

The invention relates to biocidal l-aryl-3- (2-chloroallyl) thioureas the general formula

S Cl

Il I

-C-NH-CH ₂ -C = CH ₂

RR ¹

35 which also includes the _{derivatives obtained by addition of Cl 2} or Br _{2 to the} chlorallyl group, in which R is hydrogen, chlorine, bromine, trifluoromethyl, nitro or Ci-C ₄ -alkyl and R ^{1 is} hydrogen, methyl or chlorine.

It is preferred that no more than 3 of the substituents mentioned occur in the phenyl radical. Particularly effective representatives of formula I are substituted in the 3,4- or 3,5-position of the phenyl nucleus. The substituents are preferred electronegative (= electron-attracting), but what the simultaneous presence of electroneutral Substituents such as methyl, ethyl, n-propyl, isopropyl, η-butyl or sec. Butyl does not exclude

The active ingredients of the formula (I) are against bacteria and fungi which are pathogenic to humans and plants effective.

They are very effective against members of the Phycomycetes class, e.g. B. phytopathogenic fungi such as botrytis and Pricularia, but also against various other fungal pathogens on cereals, soy, maize, Rice, vegetables, fruit growing and other crops.

They have a special effect against the following types of fungi: Cochliobolus miyabeanus species, Corticium species, Cerospora species, Alternaria species, Venturia inaequalis, Podosphaera Leucotricha, Uromyces phaseoli, Cercospora apii, Cercospora beticola, Cercospora musae, Piricularia sp, Erysiphe cichoriacearum, Penicillium digitatum, Sphaerotheca humuli, Diplocarpon rosae, Uncinula necator, Coccomyces hiermalis, Cladosporium carpophilum, Erysiphe graminis hordei, Monolinia (Sclerotinia) Laxa, Monolinia (Sclerotinia) fructico-Ia, Piricularia oryzae, Puccinia recondita, P. Coronata,

P. glumarum, Puccinia graminis tritici, Aspergillus niger, Aspergiilus terreus, Rhizoctonia, Fusarium, Verticillium. This list does not claim to be complete

The active ingredients or corresponding agents according to the invention also show a toxic effect in fungi that attack the plant in the soil and sometimes cause tracheomycoses, such as Fusarium cubense, Fusarium dianthi, Verticillium alboatrum and Phialophora cinerescens.

The active ingredients of formula (I) can also be used as bacteriostats, e.g. B. as soap additives, d. H, they can mainly be used in detergents and cleaning agents.

The compounds of the general formula are particularly suitable for this purpose

S Cl

Il I

NH-C — NH-CH, -C = CH,

(H)

proven, in which two of the substituents R, R 'and R " are identical or different and are Cl or CF3, while the third is H.

The invention also relates to microbicidal compositions which comprise as active component at least one thiourea of the general formula (I) or any of the by CI2 or Br ₂ addition to the chloroallyl derivatives obtained, in combination with one or more of the following additives: solvent , Dispersants, wetting agents, adhesives, binders, thickeners or thinners, stabilizers or other active ingredients that influence animals and plants.

Another area of application for the active components is the textile sector. From aqueous dispersion and from Solutions in organic solvents have affinity in keratin fibers and can use them against the Protect against infestation by microorganisms.

The active ingredients of the formula (I) do not have any unpleasant odor and are good for healthy skin tolerated and have none against warm-blooded animals in the concentrations usual for disinfection toxic by-products.

These properties open up a very broad field of application for the compounds according to the invention. For example, it is used in cosmetics or in body care and hygiene in general Disinfectants and preservatives for a wide variety of technical and natural products. the Application can be carried out in a wide variety of ways. As application options be for example use in the form of soap solutions, foam baths, sprays, in particular Foam sprays or solutions in organic solvents are mentioned with these applications connected biocidal equipment, which is mainly in antibacterial and antifungal directions.

The focus is on the treatment of fiber materials, as it has been shown that the active ingredients of the formula (I) are able to draw noun on a wide variety of fiber materials from an aqueous bath. It is thus possible to use these fiber materials by simply washing them with the active ingredients according to the invention detergents and cleaning agents containing permanently biocidal, preferably antibacterial and antifungal, equip and protect against attack by microorganisms and other pests.

Natural and synthetic fibers come into consideration as fiber materials. Among the natural fibers are in addition to mineral fibers, such as. B. Asbestos, especially but cellulosic fibers and especially cotton and nitrogenous fibers such as leather and wool, to mention. Both polycondensates and polyadducts are used as synthetic fiber materials Polymers, ie polymers in the broader sense, and also glass fibers into consideration The polymer fibers can be derived from natural or synthetic polymers. Fibers made from natural polymers Examples include regenerated cellulose and cellulose dibis triacetate. Synthetic polymers are derived from them for example polyester, polyamide, polyurethane, polyacrylonitrile, polyvinyl chloride and polyethylene fibers here.

Agents which contain the active ingredients according to the invention can be in various forms, e.g. B. as bar, semi-solid and liquid soaps, as pastes, powders, emulsions, suspensions, solutions in organic »solvents, as sprays, powders, granulates, tablets, in capsules made of gelatine and others Material or as ointments.

The amounts in which the active ingredients of the formula (I) are used can be within a wide range vary. As a rule, however, 1 to 30 g per liter of liquor produce the desired effect Cleaning agents generally have an active ingredient content of 0.3 to 10 percent by weight, preferably but 0.5 to 3 percent by weight.

The new thioureas of the formula (I) can be prepared in a simple manner by adding a reactive derivative of thiocarbonic acid, e.g. B. Thiophosgene, with a substituted according to formula (I) aniline Ar-NH ₂ and 2-chloroallylamine of the formula

Cl

H ₂ N-CH ₂ -C = CH ₂

(III)

optionally implemented in the order.

You can z. B. react thiophosgene with the aniline and the resulting aryl isothiocyanate Ar-N = C = S with 2-chloroallylamine of the formula (III) for reaction bring.

In reverse order you can also use a reactive derivative of thiocarbonic acid Bring 2-chloroallylamine of the formula (III) to the reaction and the isothiocyanate of the formula

Cl

S = C = N-CH ₂ -C = CH ₂

(IV)

let react with the above aniline.

The isothiocyanate of the formula (IV) can be obtained more easily in a manner known per se by reacting 2,3-dichloropropene- (I) with an inorganic rhodanide, preferably alkali metal or ammonium rhodanide. The chloroallyl group can optionally be saturated _{with Cl 2} or Br ₂ before or after the coupling to the thiourea derivative.

CF ₃

example 1

S Cl

Il I

-C-NH-CH ₂ -C = CH ₂

(D

No. 22

185 parts of 4-chloro-3-trifluoromethylaniline in 200 parts by volume of acetonitrile are added to 134 parts of (2-chloro-allyl) mustard oil in 200 parts by volume of toluene and 0.1 part of triethylenediamine. After twenty hours of heating at 80 ⁰ C is parts by volume under vacuum to about 400 concentrated, diluted with petroleum ether (50 to 70 ⁰ C), filtered, and recrystallized from toluene-petroleum ether (40 to 70 ° C)

115 to 116 ° C [Compound No. (1)].

The following compounds of the formula (V) were obtained in an analogous manner:

S Cl

Il I

-C-NH-CH ₂ -C-CH ₂

(V)

Ver Ri R ₂ R ₃ R ₄ Rs F. ⁰ C am ° C manure ⁰ C No. ⁰ C 2 H Cl Cl H H 81- 83 ⁰ C 3 H H H H H 93-95 ⁰ C 4th H C ₂ H 5 H. H H 74-76 ° c 5 H CH ₃ H H H 86-87 ° c 6th H CF ₃ H H H 79-81 ⁰ C 7th H CF ₃ H CF ₃ H 124-127 ⁰ C 8th CH ₃ CI H H H 107-108 ⁰ C 9 Cl H NO ₂ H H 135-137 ⁰ C 10 Br H CH ₃ H Br 140-141 ⁰ C 11th H H Cl H H 97-98 ⁰ C 12th H Cl H H H 101-103 ⁰ C 13th H Cl CH ₃ H H 92-93 ⁰ C 14th H NO ₂ Cl H H 114-117 ⁰ C 15th Cl H Cl Cl H 125-126 ° c 16 Cl H H Cl H 115-116 ⁰ C 17th H H C ₂ H ₅ H H 113-114 18th Cl Cl H H H 121-122 19th Cl H Cl H H 131-132 20th H Cl H Cl H 124-125 as well as the both links No.: ( C. 21 CF ₃

NH-C — NH- (

, —CBr- (

, Br

S Cl

NH-C-NH-CH ₂ -CBr-CH ₂ Br

Cl CH ₃

F. 160 to 151 ° C (decomp.)

Dust

Equal parts of an active ingredient according to the invention and precipitated silica are finely ground. By Mixing with kaolin or talc can consist of dusts with preferably 1 to 6% active ingredient content getting produced.

Wettable powder

To produce a wettable powder, for example, the following components are mixed and finely ground:

50 parts of active ingredient according to the present invention 20 parts of highly adsorptive silica 23 parts Bolus alba (kaolin) 3.5 parts of l-benzyl-2-stearyl-benzimidazole

63-disulfonate sodium

3.5 parts of reaction product from p-tert-octylphenol and ethylene oxide

Emulsion concentrate

Easily soluble active ingredients can also be formulated as an emulsion concentrate according to the following instructions:

20 parts of active ingredient 70 parts of xylene 10 parts of a mixture

from a reaction product of an alkylphenol with ethylene oxide and calcium dodecylbenzenesulfonate are mixed. When diluting with water on the the desired concentration results in a sprayable emulsion.

F. 125 to 126 ° C (decomp.)

Application example 1

Zucchetti plants were grown in the greenhouse and once prophylactically with an aqueous one Spray liquor containing 0.1% of the active ingredient, sprayed Two days later, the plants treated in this way were with spores of Erysiphe cichoriacearum DC. infected. After 12 to 14 days, the plants treated with the test preparation compound no. (1) showed a Fungal attack of 5% and the plants treated with compound no. (8) no attack, while the untreated control plants were 100% infected.

Application example 2

A mixture of equal parts of quartz sand and clay was mixed with an aqueous conidia suspension inoculated by Fusarium oxysporum, filled into pots and placed in a greenhouse cabin. After two During the day the pots were sown with melons and then with an aqueous broth containing them the equivalent of 30 kg / ha of active ingredient No. 2, evenly poured over.

The pots were kept adequately moist. After 14 days were in the treated test series

87% of the sown plants emerged healthy, compared to 6% in the untreated control vessels.

Application example 3

Bean plants were grown in the greenhouse and once prophylactically with an aqueous spray mixture, containing 0.1% of an active ingredient of the formula (1) sprayed. Two days after that, they were so treated Plants2: s with uredospores of Uromyces phaseoli (Pers.) Wint. infected and for 2 days in a Spent humid chamber. After 10 to 14 days of subsequent incubation in the greenhouse, the the following active ingredients completely kill the fungus:

In an analogous experiment with celery (Apium graveolens) as the active plant and Spetoria apii as Test fungus, compounds No. 3, 4 and 5 showed a kill of 80, 80 and 95%.

Application example 4

The active ingredients of the formula (I) show a pronounced strong action against gram-positive bacteria, especially against staphylococci and streptococci.

The antibacterial activity in the dilution test was determined as follows:

Connection no.

effect

9 100%

14 100%

15 100%

16 100%

17 100%

In an analogous experiment with grapevines as the active plant and Botrytis cinerea as the test mushroom Compounds No. 21 and 22 each showed a kill of 95%. Their effect was systematic.

Bacteriostasis and bactericides

2 (i 20 mg of active ingredient were in 10 ml of propylene glycol dissolved, of which 0.25 ml to 4.75 ml of sterile glucose broth added and then further diluted 1:10 in the tube. These solutions were then using inoculated with a bacterium and for 48 hours

? ■> 37 ° C incubated (bacteriostasis). After 24 hours Test duration was streaked 1 loop from these cultures on glucose agar plates and 24 hours at 37 ° C incubated (bactericidal). After the times mentioned, the following limit concentrations were given in ppm the bacteriostasis or bactericides determined:

bacterium Verb. Verb. Verb. Verb. Verb. Verb. Verb. Verb. Verb. Verb. Verb. No. 2 No. 7 No. 6 No. 9 No. 11 No. 12 No. 13 No. 15 No. 16 No. 19 No. 20 Trich.menta- 2.5 2.5 30th 20th 20th 20th 10 20th 30th 30th 5 grophj'tes E. coli 20th 20th 30th - 60 40 - 30th 30th - 20th Asp.niger 60 - - - - - - - - - 60 Staph.aureus 2.5 0.3 5.5 3 20th 25th 10 2 20th 30th 0.6 - = Not checked.

Application example 5

Determination of

minimal inhibitory concentration (MIC) against
Bacteria and fungi in the gradient plate test

The compounds of the formula (I) were prepared in suitable formulations (e.g. as solutions in Dimethyl sulfoxide) of a certain concentration with warm Brain Heart Infusion Agar (bacteria) resp. Mycophil agar (mushrooms) mixed The liquid mixtures were frozen on a wedge-shaped Pour the base agar layer and also solidify

, ο serene.

The test organisms were then applied in a line perpendicular to the gradient using a Pasteur pipette. After incubation for 24 hours at 37 ° C (bacteria) resp. For 72 hours at 30 ° C. (mushrooms), the length of the germs grown on the inoculation line was measured and expressed in ppm of active ingredient

Verb. No. Minimal inhibitory concentration in Fungistasis ppm Trichophyton Trichophyton Epidermophyton Microsporum Bacteriostasis Aspergillus mentagrophytes rubrum floccosum gypseum Staphylococcus Niger aureus

0.4

0.8

5.5

20th

Comparative example

The bactericidal effect of the following compounds was determined:

S Cl

NH-C-NH-CH, -C = CH ₂

according to Example 1 of the present application.

Cl

NH-C - NH-CH, - C = CH ₂

according to Example 1, Compound No. 2 of the present application.

Cl

NH-C-NH-CH ₂ -C = CH ₂

according to Example 1, compound no. 20 of the present application.

4. Cl

NH-CO-NH

// V

Cl

CF ₃

5th Cl

NH- CO - NH-

Cl

according to CH-PS 3 59 841.

method
(Agar incorporation test)

The test substance is dissolved in methyl cellosolve and a series of concentrations is produced by further dilution with methyl cellosolve. A corresponding amount of each concentration is mixed with the still liquid nutrient agar in a ratio of 1: 100. 15 ml of this are poured into Petri dishes. After solidification the plates with 1 drop of a 24 hour old bacteria suspension of Salmonella pullorum VBIZ and Escherichia coli NCTC 8196 are inoculated and incubated for 48 hours at 37 ⁰ C. Then the lowest effective concentration of the tested concentration series (calculated on the nutrient agar) is determined.

The minimum inhibitory concentrations in ppm are compiled in the following table.

Tabel

Escherichia coli NCTC 8196

30th
1.3

30th

> 300
> 300

Connection no. Salmonella pullorum VBIZ 1 10 2 6th 3 10 4th > 300 5 > 300

according to CH-PS3 59 841.

The above results clearly show that the compounds according to the invention 1 to 3 at least are 10 times more active than the known compounds 4 and 5.

Claims (1)

Patent claims: 1. l-Aryl-3- (2-chlorally!) - thioureas of the general formula _R S Cl s Il I <^ \ - NH-C-NH-CH ₂ -C = CH ₂