NO143348B - RELATIONSHIPS WITH FUNGICID AND ACARICID EFFECT - Google Patents

Description

The present invention relates to compounds with fungicide

and acaricidal activity and especially new compounds such as gene-

risk can be described as organic fluoro-imides/amides and their use.

It is known that organic fluorine imides/amides can have fungicidal and acaricidal activity. In Angewandte Chemie, volume 76, 1964, no.9, pp.808-816, a number of compounds containing an N-trihalomethylthio group with general fungicidal activity are described, and in German patent no. 1,800,836 certain tetrachlorofluoroethylthio-N-phenylsulfonamides with acaricidal and fungicidal activity.

It has been found that compounds of the formula:

wherein at least two of X-^, X2, X3 and X^ are fluorine and all X^, X2, X3 and X a which are not fluorine are chlorine, and A is selected from

where is hydrogen or a halogen atom,

preferably chlorine,

Z is CH or a nitrogen atom,

n is 0 or 1, and

R is an alkyl group with 1-6 carbon atoms, preferably methyl, or a halogen atom, preferably chlorine; where Z, n and R have the above meanings: have general activity as fungicides and in particular, compared to known fluoro-imides/amides, a surprisingly high reactivity against wood-damaging fungi and fungi that attack cereal seeds and also acaricidal activity.

The compounds of formula I are novel and form an aspect of the present invention.

Preferred compounds according to the invention are those where only two of X^, X^, X^ and X^ are fluorine and where A is a), b) or c) above.

The present compounds are prepared by condensing a halogen ethyl thiochloride of the formula

where X-^, <X>2, <X>^ and X^ have the meanings mentioned above,

with an amide or imide selected from:

where , Z, n and R have the meanings mentioned above:

where Z, n and R have the meanings mentioned above;

c) phthalimide; and

d) tetrahydrophthalimide of the formula:

A preferred method for carrying out the reaction is to

dissolve the suitable amide/imide in a mixture of chloroform and triethylamine and to this solution add the correct halogen-ethylthiochlor while dissolved in chloroform while stirring. A slightly exothermic reaction takes place and stirring is continued for around 2 hours. The reaction mixture is washed several times with water and then dried over anhydrous Na2S0^. The dry, organic layer is evaporated and gives the desired product almost quantitatively.

The compounds according to the present invention show general fungicidal activity which is surprisingly high, e.g. against discolouring fungi such as Aspergillus niger and Penicillium Spp.

In addition to their general fungicidal activity, the compounds according to the invention also show a surprisingly high activity against wood-damaging fungi, such as Coniophora cerebella, Polyporus vaporarius and Merulius lacrymans.

Compounds according to the present invention also show activity as fungicides against grain seed-attacking fungi, e.g. those that attack rye, wheat and barley, such as Urocystis occulta (stripe smut), Tilletia caries and Helinthosporium gramineum.

The starting materials used for the preparation of the compounds of formula I are either known or, if they are not, they can be prepared in the same way as known analogous compounds. For example, haloethylenes used for the preparation of the corresponding haloethylthiochlorides can be prepared as described in Houben-Weyl, Methoden der organischen Chemie (1962) volume V, part 3, pages 119-132.

The production and use of the compounds according to the present invention are further illustrated by the following examples.

EXAMPLE 1

Preparation of N-(2,2-difluoro-1,1,2-trichloroethylthio)-N-phenyl-methanesulfonamide. (connection no. 1).

To a stirring solution of 0.186 mol' of N-phenylmethanesulfonamide and 0.204 mol of triethylamine in 400 ml torr chloroform was slowly added 0.167 mol of 2,2-difluoro-1,2,2-trichloroethyl-1-thiochloride dissolved in 100 ml torr chloroform. The reaction at room temperature was slightly exothermic. Rows none persist for around two hours. After treatment twice with water, the organic layer was separated and dried over anhydrous Na 2 SO 4 and then evaporated to give a near qualitative amount of the desired product as a crystalline mass, which was recrystallized twice from anhydrous ethyl alcohol to give white crystals. with a melting point of 86.5 - 87.0°C. Elemental analysis gave the result: Calculated: C 29.16% - H 2.18% - Cl 28.70% - N 3.78% -

S 17.30%

Found: C 29.36% - H 2.17% - Cl 28.19% - N 3.80% -

S 17.7 2%

The NMR spectrum at 60 MHz in CDCl^ with TMS as internal standard showed a singlet (3 H) at 2.97 ppm (CH3-SO2-) and a singlet (5 H) at 7.40 ppm (C6H5-N-) .

EXAMPLE 2

By applying the procedure in example 1, but with corresponding changes in the starting materials used, the following compounds were prepared: Compound no. 2: N-(1,2-difluoro-1,2,2-trichloroethylthio)-N- phenyl-methanesulfonamide. M.p.: 64-72°C. Compound No. 3: N-(1,2,2-trifluoro-1,2-dichloroethylthio)-N- phenyl-methanesulfonamide. M.p.: 62.5°C. Compound No. 4: N-(2,2-difluoro-1,1,2-trichloroethylthio)-N- (4-chlorophenyl)methanesulfonamide. Temp. 88.1-90.1°C. Compound No. 5: N-(2,2-difluoro-1,1,2-trichloroethylthio)-N- (3-Chlorophenyl)methanesulfonamide. Liquid. Compound No. 6: N-(2,2-difluoro-1,1,2-trichloroethylthio)-N- (3-pyridyl)methanesulfonamide. Slow and incomplete

constant crystallization.

Compound No. 7: N-(2,2-difluoro-1,1,2-trichloroethylthio)-N-phenylchloromethanesulfonamide. M.p.: 57.5-59°C. Compound No. 8: N-(2,2-difluoro-1,1,2-trichloroethylthio)-N-(2-methylphenyl)chloromethanesulfonamide. Slow and

incomplete crystallization.

Compound No. 9: N,N-dimethyl-N'-(2,2-difluoro-1,1,2-trichloroethylthio)-N1-phenylsulfamide. Temp. 75.0-76.3°C. Compound no. 10: N,N-dimethyl-N'-(1,2-difluoro-1,2,2-trichloro-ethylthio)-N<1->phenylsulfamide. Temp. 65-67°C.

Compound No. 11: N,N-dimethyl-N'-(2,2-difluoro-1,L,2-trichloroethylthio)-N'-(4-methylphenyl)sulfamide. Temp. 7 2-74°C.

Compound No. 12: N,N-dimethyl-N'-(2,2-difluoro-1,1,2-trichloroethylthio)-N'-(4-chlorophenyl)sulfamide. Liquid. Compound No. 13: N,N-dimethyl-N'-(2,2-difluoro-1,1,2-trichloro-ethylthio)-N'-(3-pyridyl) sulfamide. Temp. 75.8-78.8°C.

Compound No. 14: N,N-dimethyl-N<1->(1,2,2-trifluoro-1,2-dichloro-ethylthio)-N'-phenylsulfamide. M.p.: 71-76°C.

EXAMPLE 3

Preparation of N-(halo-ethylthio)-phthalimides.

To a suspension of 0.1 mol of potassium phthalimido in 200 ml of benzene was added a solution of 0.1 mol of the corresponding halogen, ethyl thio chloride in 50 ml of benzene. The reaction was exothermic and the temperature was kept below 30°C. After complete addition, the mixture was heated to around 70°C and allowed to stand overnight. The benzene was removed under reduced pressure and the residue dissolved in a mixture of chloroform and water. The chloroform layer was separated, washed twice with a cold aqueous sodium hydroxide solution and twice with water, dried over sodium sulfate, filtered and evaporated. A white solid formed.

According to this procedure, the following was produced:

Compound No. 15: N-(2,2-difluoro-1,1,2-trichloroethylthio)- phthalimide, mp: 103-105°C.

EXAMPLE 4

Preparation of N-(halo-ethylthio)-tetrahydro-phthalimides.

A first solution was prepared by mixing together 100 ml of water and 0.05 mol of the corresponding halogen ethyl thiochloride. Another solution containing 0.05 mol of tetrahydrocalcimide and 0.05 mol of sodium hydroxide and 100 ml of water was prepared by mixing the ingredients together. The second discharge was added to the first discharge over a period of 5 minutes at 10-15°C under agitation and dressing. A solid formed and the mixture was stirred for an additional 30 minutes. 100 ml of chloroform was then added. The chloroform solution was dried over magnesium sulfate and evaporated under reduced pressure to give a light yellow oil. On standing, crystals formed. 10 ml of n-pentane was then added and the crystals were filtered off and washed with further n-pentane to give white crystals.

According to this procedure, the following was produced:

Compound No. 16: N-(2,2-difluoro-1,1,2-trichloroethylthio)- tetrahydrophthalimide. Temp. 45°C.

Compound No. 17: N-(1,2,2-trifluoro-1,2-dichloroethylthio)-tetrahydrophthalimide. White oil.

EXAMPLE 5

Test for general fungicidal activity shown by activity against Pullularia pullulans (P 268) and Aspergillus niger (EMPA).

The compound to be tested was dissolved in a suitable solvent such as dimethylformamide, ethyl acetate or water, and 0.3 ml of the solution was evenly distributed over a piece of filter paper (What-man no. 40). The paper surface was 19.5 cm 2. After evaporation of the solvent, the paper was placed in a plastic bag which was sealed and sterilized by irradiation. For the test, the paper was placed on an agar medium in a sterilized Petri dish and the medium was inoculated with spores of the corresponding fungus. After 10 days of exposure at 29°C and 85% relative humidity, the test vessel was inspected. Samples that showed no sign of growth on or in a narrow zone around the filter paper were considered positive.

The following compounds of formula I were tested by this method and the following table shows the lowest percentage concentration required to give a positive sample.

To provide a comparison with known compounds, the known fungicidal compounds, N-(2-fluoro-1,1,2,2-tetrachloro-ethylthio)-N-phenylmethanesulfonamide (Stauffer Chem. Co. R 10044) and N- (1,1, 2, 2^tetrachloroethylthio)-tetrahydrophthalimide (Difolatan) . tested.

For both of these compounds, the concentration required for a positive sample using the preceding conditions was 0.01% for both fungi.

EXAMPLE 6

Test for activity against wood-damaging fungi.

The activity against wood-damaging fungi was tested on Coniophora cerebella. Pine wood samples with dimensions 7 cm x 1.6 cm x 0.2 cm were dried for 24 hours at 103° and then weighed.

A concentration series of 1, 0.5, 0.25 and 0.125% of the compound to be tested was prepared as a solution in white spirit containing 9% of an alkyd binder. The wood samples were impregnated by dipping in one of these solutions for a short period of time. The wet samples were weighed, and the intake was around 100 kg of the discharge per m 3 wood. The samples were then dried for 2 days at room temperature.

Six samples were impregnated with each concentration of the test compound. Three of them were packed in sterilizable plastic bags and sterilized by UV irradiation or gamma irradiation and the other three were licked for 3 days in running water at 20°C, the replacement of water being around 6 times a day. After washing, they were dried for 2 days at room temperature and then packed and sterilized as mentioned above.

Glass bottles containing 500 ml of soil specially added with nutrients for the growth of Coniophora cerebella were sterilized by autoclaving for 3 hours at 120°C and then cooled. The three samples were placed in the bottles, the soil was inoculated with Coniophora cerebella and the incubation was carried out for 4 weeks at 22°c and 70% relative humidity.

After incubation, the sample was carefully stroked and then dried at 103°C and weighed. The weight loss of each sample was calculated as a percentage of the original dry weight.

The data given in the following table shows the weight loss (as a percentage) in an average of 3 samples.

For comparison purposes, the following well-known wood preservatives were tested in exactly the same way:

q pentachlorophenol + abietylamine (1/1 molar)

(3 pentachloro phenol + tributyltin oxide (1/1 molar)

Y dichlorofluanid

The test without tilting gave the following results:

As a control, 8 samples were carried out with non-impregnated samples; the weight losses were between 18% and 40%.

EXAMPLE 7

Uninfected grain seed and grain seed infected with specified fungi:

Wheat (Kranic) with Tilletia caries

Rye (Petkus II) with Urocystis occulta and

Barley (Lami) with Helminthosporium gramineum

was pre-treated and sown in small plots 1 m x 0.5 m in Jyl1and, Denmark

All the seeds were pretreated with an emulsion of olive oil in water and then treated for 5 minutes with a powder that was either inert or contained either 200 or 2000 ppm of the compound to be tested. The connections made were. three compounds according to the invention, three other compounds for comparison purposes, and mercury in an amount of 20 ppm. The wheat and rye were sown in mid-October 1975 and the barley in mid-March 1976. The plots were inspected in early August 1976 and the number of individual plants up to and including 10 infected with fungal disease was noted (where more than 10 individual plants were infected the result was stated in the following table as 11 > 10").

The results obtained are shown in the following table; each result is an average number of identical sown plots.

EXAMPLE 8

The fungicidal and acaricidal properties of compound 1 according to the invention in the treatment of apple trees; were tested and compared with those of an analogous compound, N-(2-fluoro-1,1,2,2-tetrachloroethylthio)-N-phenylmethanesulfonamide (Stauffer Chemical Co.; compound R-10044) and three commercially available plant protection compounds, maneb (ditan), captan (ortho-cid) and binapacryl.

Cox Orange Pippin, Golden Delicious and Cortland apple trees were sprayed with aqueous dispersions* of the following:

Each compound was used in an amount of 0.2, 0.6 and 2 kg of active ingredient per hectares. Each variation of the spray program on 5 trees.

No trees in the experiment, including those that were untreated, were attacked by Venturia inaequalis.

All trees treated with compound 1 (HKA-3) and R-10044 were attacked by powdery mildew. Compound 1 applied at 2 kg of active ingredient/ha showed somewhat weaker attack by powdery mildew compared to the powdery mildew attacks in untreated trees.

Attacks by spider mites (Tetranychus urticas) were established

as stated in the following table:

No differences in the results were detected with different varieties of apples.

The table shows that compound 1 (HKA-3) provides better protection against attack by spider mites than the known acaricide, binapacryl.

Claims (2)

1. Compounds with fungicidal and acaricidal action, characterized in that they are covered by the formula wherein at least two of X^, , X^ and X^ are fluorine and one each of X-^, X2, and X^ which is not fluorine is chlorine, and A is selected from wherein R^ is hydrogen or a halogen atom , Z is CH or a nitrogen atom, n is 0 or 1, and R is an alkyl group of 1 to 6 carbon atoms or a halogen atom; wherein Z, n and R have the above meanings; 2. Use of compounds of formula I as defined in claim 1 as acaricide and fungicide.