CS195695B2 - Method of preparing substituted n-/2,2-difluoralkanoyl/-o-phenylendiamines - Google Patents

Description

The invention relates to a process for the preparation of novel ring-substituted N- (2,2-difluoroalkanoyl) -O-phenylenediamine amines which are useful as parasiticidal compounds and anthelmintic agents.

The control of animal parasites is one of the oldest and most important problems of animal production. Many types of parasites affect all animal species. The vast majority of animals are affected by free-flying parasites such as flies, crawling ectoparasites such as lice and aphids, drilling parasites such as larvae and flyworms, and microscopic endoparasites such as coccidia as well as larger endoparasites such as worms. Thus, parasite control in a single host is a complex problem with many side problems.

Parasites from the group of insects and mites that eat live tissues of host animals are harmful. This group includes parasites of all economic animals including ruminants and single-stomach mammals and poultry and companion animals such as dogs.

. Recently, many methods for controlling these parasites have been tested. Cochllmyia hominivorax worms were practically exterminated in Florida by the release of a large number of sterile male flies. 195995

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The method is, of course, applicable, only in an easily isolated region. Free-flying insects are usually controlled by conventional methods, such as vermin dispersed in air and contact insecticides and fly traps. Climbing parasites inhabiting the skin are usually controlled by dipping, soaking or spraying the animals with the appropriate parasiticidal agents.

. Certain, progress has been made in the systematic control of certain parasites, particularly those living in the host 's animal migrating through it. Systemic control of animal parasites was performed by absorption of the parasiticidal agent in the bloodstream or other tissue of the host animal. Parasites Eating: no, or who come into contact with tissue containing a parasiticidal substance, are either killed by ingesting the parasiticidal substance or having come into contact with it. Some phosphate, phosphoramidate and phosphorothioate insecticides and acarides have been found to be sufficiently non-toxic and can be used. systemically in animals.

Rumanowski, U.S. Patent 3,557,211, discloses N, N-white (acetylo-o-phenylenediamines which are useful for controlling plants, fungi and fungi).

One feature of the invention is a process for preparing compounds that are effective, systemic parasiticides.

The present invention relates to a process for the preparation of novel ring-substituted N- (2,2-difluoroalkanoyl) o-phenylenediamines of the formula II.

where

R 0 is a 2,2-difluoroalkanoyl radical of the formula. ............ o '--------------.— · .......

II — C — CF2 — Y, where

Y is hydrogen, chloro, fluoro, difluoromethyl or perfluoroalkyl of 1 to 6 carbon atoms;

ju ¹ hydrogen atom, the remainder of formula O

II \ .....

—C — o-γΐ, where

.. Y ¹ :: is. alkyl of 1 to 4 carbon atoms, benzoyl, naphthoyl or substituted benzoyl of formula

wherein each of Z 'is independently halogen or nitro, Z'; Yippee. alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms, p is 0, 1 or 2, q. is Q or 1 and the sum of p and q is 1 to 3 ’,

R ^{4 is a} nitro group, Λ '; Ø ⁵ is; trifluoromethyl, and R ⁴ and R ⁵ are meta relative to each other, wherein when R ¹ is a hydrogen atom, the ortho position on the ring relative to the -NH-R ¹ group contains one of the radicals listed for R ⁴ or R ⁵ .

The compounds of formula I are prepared by introducing a characteristic 2,2-difluoroalkanoyl group into the corresponding corresponding diamine of the starting material. The introduction of this group can be carried out by any of the available acylation reactions using any of the various types of acylating agents of formula IV,

HO — C — CF2 — Y · ^(IV) wherein Y is as defined above, or 2,2-difluoroalkanoyl halides of the general formula V hal — C — CF 2 —Y, · · ... ||

O /// (V) or 2,2'-difluoroicanoic anhydrides of general formula VI, o-r-o-CF2-Yi2

II c

(VI) wherein Y is as defined above. The diamond starting materials with which the acylation reactions are carried out are different.

A process for preparing a compound of formula (I) is characterized by acylating a compound of formula (VIII),

wherein the different symbols have the meanings given above, with an acylating agent of formula IV, O

II · ·. HO - C - CF 2 - Y (IV) wherein Ϋ is as defined above, or a halide or anhydride of a compound of formula IV.

In the case of compounds of formula I wherein R ¹ is hydrogen, the starting compound is a compound of formula XI

and introducing one acyl group (leaving R ¹ equal to the hydrogen atom).

If, on the other hand, R ¹ is any residue other than hydrogen, the appropriate starting material is a compound bearing the desired residue. R ^{1 of} formula XIV,

wherein the symbols have the meaning given above and the characteristic R 0 group is similarly introduced by acylation.

While the synthetic processes described above are conventional and preferred, other methods may be used. For example, when R ¹ is an acyl group, the R ¹ group is preferably introduced in some cases only after the introduction of R 0. However, due to the activating effect of α-fluoratoms on acylation, it is generally preferred that groups other than 2,2-difluoroalkanoyl groups are already present at the time; when this group is being introduced.

The preparation of amides by acylation of the corresponding amines with various aoylating agents is. by a known synthetic method. These preparations are carried out according to conventional methods used for this purpose. Thus, if the acylating agent is an anhydride, the reaction is preferably carried out at room temperature, as an excess of the anhydride may be used as the solvent, except. cases of aria where R ¹ - is a hydrogen atom. If an acyl halide is used as the acylating agent, the reaction is necessarily carried out in the presence of a hydrogen halide acceptor and preferably in the presence of an inert solvent. Ia and the reaction mixture is preferably cooled to temperatures of 0 to 10 ^Q C. In the case of any of acylating agent, the product is separated by conventional methods and may be purified, if desired by known methods ...

For simplicity, starting materials and products. they call, where possible, o-phenylenediamines. In accordance with conventional nomenclature practice, the identification of the various substituent positions is as follows:

wherein either the nitrogen atom contains an alkanoyl or other (R °, R ¹ ) substituent, the ring position numbers are identified as prime numbers to distinguish from the positions on the R ° or R ¹ substituents.

In the foregoing definition of the compounds of formula I and in this description and the definition of the present invention, each term "hal" and "halogen", unless specified, but used alone or in conjunction as "halogenated alkanoyl", refers to bromine atoms only. , chlorine, fluorine or iodine. .

The basic and. Distinguishable structural feature of the compounds of formula I is 2,2-difluoralkaňoylový radical (R ^@ j, examples of such residues are the following: difluoroacetyl, trifluoroacetates 1 DIF iuorchloracetyl, pentafluoro luorpropionyl, heptafluorbutýryl, nonafluorvaleryl, 2,2,3,3- tetrafluoropropionyl, undecafluorhexanoyl, tridekafluorheptanoyl, pentadecaflunrnktanoyl. ···

Preferred R c groups are trifluoroacetyl, difluoroacetyl, difluorochloroacetyl, 2,2,3,3-tetrafluoropropionyl.

The starting materials used in the process of the invention are prepared by known methods and some of them are commercially available. Starting materials of formula XI,

wherein R ⁴ and R ⁵ are as defined above, are prepared by multistep syntheses that are necessary to introduce the desired groups. Most preferably, one or both of the NH 2 groups are introduced by conversion of a halogen group. The amino group or amino groups can also be introduced by nitration and subsequent reduction. The various synthetic steps are generally and most preferably carried out with starting materials which already contain groups R ⁴ and R ⁵ . However, sometimes it is preferred that these substituents, for example nitro or halogen, are introduced simultaneously with the synthetic steps leading to the introduction of amino groups.

Compounds of formula I wherein R 6 is other than hydrogen are generally prepared from starting materials already containing R ¹ . The starting materials are prepared from odpovídajících- diamine starting materials described above by reaction with an appropriate acyl halide or when R ¹ is -C-OY '

With the corresponding lower alkyl or phenyl haloformate. Alternatively, however, these materials can be prepared from o-nitroanilines of the general formula β

wherein R ⁴ and R ⁵ are as defined above, acylated and followed by reduction, both. the reactions are carried out by well-known procedures. ·

The synthesis of compounds of formula I is illustrated in more detail in the following examples.

Example 1 _;

Fine, ground 3-trifluoromethyl-5-nitro-o-phenylenediamine (2.2 g), triethylamine (1.0 ml) and chloroform (10 ml) were mixed and mixed with the addition of trifluoroacetic anhydride (2). up to 3 ml in 20 ml chloroform). The addition was carried out gradually over 20 minutes at room temperature. The resulting reaction mixture was filtered and the product N ¹ -trifluoroacetyl-3'-trifluoromethyl-5'-nitro-o-phenylenediamine was recrystallized from benzene and had a melting point of 201-202 ° C.

Analysis for C 9 H 5 F 6 N 3 O 3;

C 34.08, H 1.58, N 13.24. Found C 34.24, H 1.60, N 13.24.

Example 2

3-Nitro-5-trifluoromethyl-o-phenylenedlaxine (5.0 g) was treated with 15 ml of pyridine and cooled to 0 ° C. Chlorodifluoroacetyl chloride (3 mL) was then added with stirring over 20 minutes. After standing at 20 ° C for 1.5 hours, the reaction mixture was mixed with 150 g of ice and 20 ml of hydrochloric acid and the desired Nt-chlorodifluoroacetyl-5'-nitro-5'-trifluoromethyl-o-phenylenediamine precipitated. The product was filtered off, recrystallized from benzene and showed m.p. 186-188 ° C.

Example 3

N ² -benzoyl-6-nitro-4-trifluoromethyl-o-phenylenediamine (3.2 g) and excess trifluoroacetic anhydride were combined and allowed to stand overnight. Excess trifluoroacetic anhydride and the corresponding by-product were evaporated in vacuo to give N ¹ -trifluoroacetyl-N ² -benzoyl-6'-nitro-4'-trifluoromethyl-O-phenylenediamine, which after crystallization from benzene had bt 193 up to 195 degrees Celsius.

He attaches

The other compounds of the invention were prepared according to the preceding examples using analogous starting materials. These compounds are as follows:

N ¹ -trifluoroacetyl-3'-nitro-5'-trifluoromethyl-o-phenylenediamine, mp 194-195 ° C, prepared by reacting trifluoroacetanhydride with 3-nitro-5-trifluoromethyl-o-phenyleridlamine;

N ¹ -trifluoroacetyl-N ² -naphthyl-6'-nitro-4'-trifluoromethyl-o-phenylenediamine, mp 200-204 degrees Celsius, prepared by reacting trifluoroacetate anhydride with N, N-naphthoyl-e-nitro-α-trifluoromethyl-phenylenediamine;

NMrifluoro-Cetyl-N ² - (p-t-butoxybenzoyl) -4'-trifluoromethyl-6'-nitro-o-phenylenediamine,

b. mp 172-174 ° C;

N ¹ -trifluoroacetyl-N ² - (p-nitrobenzoyl) -4'-trifluoromethyl-6'-nitro-4-phenylenediamine; mp 210-212 ° C;

N -heptáfluorbůíyryl Nitta-3'-5'-trifluoí'methyl-o-phenylenediamine, mp 118-120 DEG C;

Ni-pentafluoropropionyl-S-nitro-SM-trifluoromethyl-o-phenylenediaroin, m.p. 161-163 * 0;

N-trifluoroacetyl-N ^2- methoxycarbonyl-4'-trifluoromethyl-6'-nitro-O'-phenylenediamine, mp 129-130 ° C; ; / '' ··. N ¹ -pentafluorooctanoyl-3'-nitro-5'-trifluoromethyl-6-phenylenediamine, mp 111-113 ° C;

N ¹ - (2,2,3,3 -tetraf luorproplonýl) ² -N-methoxycarbonyl-6'-nitro-4'-trlf luqrmethyl-o-phenylenediamine · fe, mp ^129-130? C;

N ^1- (2,2,3,3-tetrafluoropropyl) -3'-nitro-5'-trifluoromethyl-o-phenylenediamine, mp 144-145 ° C, prepared by reacting 2,2,3,3-tetrafluoropropionyl bromide with 3-nitro-5-trifluoromethyl-phenylenediamine;

N ¹ -trifluoroacetyl-N ² - (3-6-dichloro-2-methoxybenzoyl) -6'-nitro-4'-trifluoromethyl-o-phenylenediamine, mp 200-201 ° C, prepared by reaction N ² - ( 3,6-Dichloro-2-methoxybenzoyl) -6-nitro-4-trifluoromethyl-α-phenylene diamine with trifluoroacetic anhydride.

All compounds of formula (II) may be formulated to be useful as herbicides. These compounds can be used in such a way that a broad herbicidal effect is obtained; thus, in the broadest sense, the invention relates to a method of application characterized in that:. a plant inhibiting amount of one of the ring-substituted N- (2,2-difluoroalkanoyl) -o-phenylenediamines of the formula Π is applied to plant parts such as a scape, leaves, flowers, fruits, roots or seeds or the like of a plant production unit. However, these compounds can also be used by utilizing selective herbicidal activity. How are you

199699, a mixture of more than one compound can also be used to achieve a herbicidal effect. If atrophy is used, the amount of each individual compound may be reduced so that the mixture exhibits only the desired herbicidal effect.

It is not critical for the herbicidal utility of the compounds whether undesirable vegetation is completely controlled; it is sufficient if undesirable vegetation is only inhibited. In particular, as far as the selective effect is concerned, inhibition of not complete killing is sufficient, especially when combined with natural conditions, such as limited humidity, which has a selectively inhibited effect on vegetation more favorably than on useful plants.

The compounds of formula II are suitable for various variations of herbicidal applications.

The compounds of formula II exhibit low mammalian toxicity, relative to benzl imidazoles. In addition, the compounds of formula II may be dispersed as an aerosol mixture containing the poison or more active compounds of the invention. This mixture is prepared according to conventional methods, wherein the active substance is dispersed in a solvent and the resulting dispersion is mixed with the propellant in a liquid state. These variations as to the use of a particular agent and the type of vegetation to be treated determine the solvent requirements and the active compound concentration therein. Examples of suitable solvents are water, acetone, isopropanol and 2-ethoxyethanol.

Suitably the results are obtained when the active substances of the formula II or a mixture containing these active substances are mixed with other agriculturally used materials to be applied to the plants, plant parts and their surroundings. These materials include fertilizers, fungicides, insecticides, other herbicides and soil conditioners.

The various compounds of formula (II) to be used as active herbicidal agents are evaluated after application on emergence in different. plant species. In this evaluation, a soil containing one part sand and one part crushed top soil layer is prepared, blended perfectly in a cement mixer.

4.5 L of soil is placed in a 25 X 35 cm galvanized tin bowl and the basement is under the rim. 2.5 cm deep grooves are made in three rows in two fifths of the dish. These grooves are planted with four corn grains, five cotton seeds and five soybean seeds. In the remaining four grooves, an approximate number of each of the ten is sown in the remaining soil

The following seeds, each species in a single row, are: • Seeds of 80 to 100 seeds, Wormwood 40 to 50 seeds, 150 to 250 seeds and 100 to 150 seeds.

A further sufficient amount is then added to sufficiently cover the area.

Thus the weed seeds are covered with a layer of about 6 mm and the seeds of the useful plants with a layer of about 3 cm.

In determining the effect of the composition as a herbicidal composition for pre-emergence use, the area is prepared as described above and placed in a turntable and air vented chamber on the day of sowing or the following day. The herbicidal blend of the dry spray emulsion or wettable powder type is applied to the surface with a modified De Vilbis atomizer attached to an air source. Twelve and a half milliliters of the mixture to be used. test, then apply to. each area either in the sowing depot or in the following children. The severity of the lesion and the observation of the lesion type are performed 11 to 12 days after treatment. Damage shall be assessed on the following scale:.

—- No damage, - slight damage,

2 - moderate damage, - considerable damage, - death.

Where more than one determination was made at the indicated amount, the average was calculated to assess damage. Each test compound is sprayed by one of the following procedures. In one test, the compound is wetted by mixing in a mortar with one part polyoxyethylene sorbitan monolaurate. Five hundred parts of water are slowly added to the resulting cream-colored paste to give an aqueous dispersion with a base concentration of 0.2%. The dispersion is suitable for spray application. In the second ’procedure. Dissolve the compound in one part of acetone and dilute the acetone solution with nineteen parts of water containing 0.1% polyoxyethylene sorbitan monolaurate.

In the following Table I the evaluation results are shown, column i shows the name of the test compound, column 2 the amount in kilograms per hectare in which the compound is applied to the test area, and the remaining columns indicate the degree of damage to certain plant seeds or plant seedlings. ' , Μ «d cd •--i 'Φ

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The compounds of formula II also exhibit insecticidal and arachnicidal activity. These compounds are useful for the control of bivalve mites and arthropods of the Arachnidea class, whereby it is possible. The selection of quantities is such as to prevent phytotoxicity and the compounds may be used to control those insects and arthropods of the Arachnidae class that occur on the roots or aerial parts of the plants. These compounds are effective, for example, against such arthropods of the Arachnidae class, such as the spider mite (Epitetrahychus altheae), the spider mite (Panonychus citri), the spider mite (Tetranychus telarius), the spider mite (Tetranychus pacificia, Bryanus pacificus), (Dermanyssus gallinae), various ticks and various spiders. The compounds of this subgroup are also active against insects of various orders including Epi.lachna varivéstis, Anthonomus grandia, Grambus caliginosellus, Oulema melanopus, various beetles of the Altica and Epitrix species, drilling insects, Leptinetarsa decemlineata, grain beetles, Hyperia postusumum, Anthrenus confusumum, Anthrausususumum, , larvae of infecting infants, Slothophilus oryzáe, Conotrachelus nenuplar, white greetings, Aphis gossypii, Macrosiphuni rosae, Rhopalosiphuni maldis, Acyrthosiphon onobrychls, insects of the genus Pseudococcidae, insects of the genus Coducis, insects of the genus Coccidae, His fobae, Lygus lineolaris, Leptocoris trivlttatus, Cimex lectularus, Anasa tristis, Bllssus ipucopterus, Musea 'domestics, - Aedea aegypti, Storaoxys caltritrans, Haomatobia. irritans, Hylemia brascicae, .Psila rosae, Prodenia eridania ,. caterpillars of the genus Noctuidae, moths, Plodta interpunotella, Heliothis zea, Ostrinia nubilalis, Trichoplusia ni, Alabama argillacea, Thyridopteryx aphemeraefomis, Spodoptera fruglperda, Blattella germanica and Periplanera americana.

The insecticidal and arachnicidal effect of the compounds of formula II is illustrated by the following tests on representative insects and arthropods of the class Ardchnidae.

Epiiachna varivéstis (Coleoptera)

The trunks of four six-day Bountiful snap beans, containing two leaves of approximately 12.5 cm ² , are placed in water. The leaves are sprayed with about 5-10 ml of a preparation containing a predetermined amount of test compound. Half of the formulation was sprayed on the top surface and half on the leaf surface using a De Vilbris atomizer and a pressure of 68.6 kPa from a distance. 45 cm from the leaf. After drying the leaves, the leaves are cut off from the Shape and placed separately in Petri dishes. The third instar larvae of Épilachha varivestes, grown on Bountiful snap bean leaves, are placed on each leaf. Controls consist of two Hsts sprayed with 5 n? ¹ preparation containing 500 ppm of N- (1,2'-dicarbethoxyethyl) -0,0-dimethylphosphorothioate (corresponding standard), two sheets sprayed with the preparation without active ingredient and: two sheets maintained as a treated control. After 48 hours, mortality is calculated and the amount of food eaten is measured. Dying larvae count as. The following toxicity scale was used:

percentage of dead ratings

at — 10 · 11-20 • ·. 0 1 '- 21—30 · .2 '· - 31—40 3. 41-50 4 51—60 61—70 - 5 . · 6 - 71—80 81—90 .. - · 7 • -8 ’. 91—100 · 9

The compounds so used, the amounts used and the results are shown in the following table. If it was. made more. than, one experiment for the indicated amount i gives an average of several results.

compound

Table IV. , ppm toxicity for Epilachna varivestis

NMrifluoroacetyl-3'-nitro-5'-trifluoromethyl-o-phenylenediamine.

Difluorochloroacetyl-3'-nitro: 5'-trifluoro-. methyl-o-phenylenediamine ^:

N ¹ -trifluoroacetyl-N ² -benzoyl-6'-nitro-4'-trifluoromethyl-o-phenylenediamine

NMrifluoroacetyl-N ² - (p-nitrobenzoyl) ->.

-4'-trifluoromethyl-1'-nitro-o-phenylenediamine

N ¹ -fluoraphthetyl-N ² -methoxyethoxycarbonyl-4'-trifluoromethyl-6'-nitro-phenylenediamine

N ^1- (2,2,3,3-Tetrofluoroproplonyl) -N ² -methoxycarbonyl-6'-nitro-4'-trifluoromethyl-phenylenedlamine

1000 9.0 500 9.0 250 9.0 100 ALIGN! 9.0 50 9.0 1000 9.0 '500 9.0 250 9.0 100 ALIGN! 8.0 50 9.0 1000 7.0 500 ... 9.0 250 ' 7.5 1000 9.0 500 9.0 1000 9.0 500  9.0 250 9.0 100 .. -. 9.0 , 50 ·· . 9.0 íboo: · ' - 9.0 500 9.0 250 9.0 100 ALIGN! 9.0

The Birth of Eridania (Lepldopteraj

Ten uniform Prodenla eridaiiia larvae, i - 1.5 cm long, grown on Henderson lima beans, are placed on torn leaves of beans in Petrl dishes. . Bean leaves are obtained and sprayed with insecticide in the same manner as the leaves listed in the Epilachna varivestis test. The corresponding standard for this case is the leaves sprayed with 5 ml of 100 ppm DDT solution. The number of compounds died

N4-Difluorochloroacetyl-3'-nitro-5'-trifluoromethyl-o-phenyleneamine

NMrifluoroacetyl-N ² - (p-nitrobenzoyl) -4 '-_____________

-trifluoromethyl-6'-nitro-o-phenylenediamine.

Aphis gossypii (Hemiptera)

Four blue hubbard pumpkin seeds are sown in a vermiculite container, and the containers are watered from below. After six days, two weaker plants are cut off and one uterus and primary leaves are removed from each of the remaining plants. The remaining uterus is infected with 100 individuals of Aphis gossypii from a stock colony by feeding the uterus to the infected cannabis at 48 hours after spraying and re-dying larvae counted as dead. Missing larvae likely to be eaten are considered to be alive. The same scale as the Epilachna varivestis test was used for evaluation,

The compounds so used, the amount used and the evaluation results are shown in the following table. If more than one experiment was performed, the results are an average of several results.

b ulk and V ppm toxicity for Prodenla eridania

1000 8.5 '1000 9.0 Lose stock colonies and aphids are allowed to climb. After climbing, the leaf is discolored. After 48 hours, the infected leaves are sprayed with a preparation containing a graded amount of insecticide using a De Vilbris atomizer of 68.6 kPa at a distance of 30 to 37.5 cm from the plant. Controls consisting of two infected unprotected pumpkin plants and two infected plants sprayed with a preparation containing 100 ppm S- (1,2-dlkar195695 bethoxyethyl) -O, O-diinethylphosphorodithioate as standard. Mortality is. scored 24 hours after spraying using a 10x magnification microscope. The same scale as before was used for the evaluation.

The compounds used, the amounts used and the results are shown in the following table. If multiple experiments were performed, the values are the average of several results.

Table VI

compound PPm toxicity to Aphis, gossypii NMrifluoroacetyl-T-nitro-Sritrtfluoromethyl- 1000 9.0 -o-phenylenediamine 500 9.0 250 9.0 100 ALIGN! 8.0 50 7.0. NMifluorochloroacetyl-S-nitro-S-trifluoro- 1000 η n methyl-o-phenylenediamine 500 9.0 250 8.5 100 ALIGN! 8.0 N ¹ -trifluoroacetyl: 3Strifluoromethyl-5'-nitro- 1000 9.0 -o-phenylenediamine . 500- 9.0 250 _: 9,0. Tetranychus urtlcae (Acarlna) according to the invention, according to the test. 48 hours after spraying, Spider mites, grown on greens mortality. The same rating will be used bean plants are transferred to the grate. as in other tests. . liny pumpkin. Pumpkin plants are maintained so Used compounds, doses used and an infection could have taken place. Infikova- evaluation are given in the following table. Pumpkin plants are then sprayed with dough- ce. ným. preparative; containing a compound , · .R. Table VII compound '; Ppm toxicity, to Tetranychus • ..... '...' ..... ..... urticae N * ¹ -trifluoracetýÍ ^{3'-Nitro-5-Trifluoro} luormethyl-. 1000 9.0 -o-phenylenediamine 500 9.0 V. ¹ . 250 9.0 100 ALIGN! 9.0 ... ‘ 50 8.5 Ni-pentfluorgToplQnyl-3´-nitro-5´-trifluoro- 1000 9.0 methyl-o-phenylenedlamine 500 9.0 250 , 9.0 .'•and.' ⁷ · / . .100 9.0 ⁵⁰ 8.5 NMlfl00blogerCtyl-3'-nitro-5'-lrifluor- 1000 9.0 methyl-o-phenylenediamine 500 9.0 250 9.0 100 ALIGN! 8.0 50 9.0 N-Trifluoromethyl-α-trifluoromethyl-S-nitro- 1000 9.0 -o-phenylenediamine < 500 9.0 '!' ·; , · * 250 9.0 100 ALIGN! 9.0 50 8.0 N-Trifluoroacetates | -; N-Methoxycarbonyl-4´- 1000 9.0 -trlfluoromethyl-6'-nitro-o-phenylenediamine 500 9.0 ' .250 7.5 N ^1- (2,2,3,3-tetrafluoropropionyl) -N ² -metho- 1000 9.0 xycarhonyl-6'-nitro-4'-trifluoromethyl-o-phe- 500 6.5

nylendlamine

195

Oncopelitis fasclatus (Hemiptera)

Adult Oncopelitis fasciaťus is cooled and placed in test cages. The beetle-containing cage is sprayed with 5 ml of the test preparation containing a predetermined amount of De-Vilbiss insecticide at an atomizer pressure of 68.6 kPa from a distance of 80 cm from the top of the cage. Once the cage dries, the beetles are fed and watered for 48 hours. As a corresponding standard, the. using a preparation of 500 ppm of 2- (1,2-dicarbethoxyethyl) O, O -dimethylphosphorothlolate and two unprotected sprouts are kept as a control, mortality counts after 48 hours, dying adults are counted as dead. same scale as previous tests.

The compounds used, the amounts used and the test results are shown in the following table.

Bulk VIII compound ppm Tocopelitis fasclatus toxicity

NMrifluoroacetyl-S-nitro-Sulfifluoromethyl-o-phenylenediamine

NMifluorchloracetyl-3´-nitro-5´-trifluoromethyl-o-phenylenediamine

NMrifluoroacetyl-3 ^ trifluoromethyl-5 ’

-nitro-o-phenylenedlamine

N-Heptafluorobutyryl-S-nitro-S-trifluoromethyl-o-phenylenediamine

- · *. A · · · ·

Domestica (Diptera)

Breeding cages containing four days old adult house flies are cooled to 2 to 4 ° C for about one hour. One hundred flies are transferred from the breeding cage to each cage using a small blade. The flies are kept in the germ for about one to two hours at 21 to 27 ° C and then sprayed in the same manner as described for Oncopelitis fasclatus, five milliliters of test preparation. Two unprayed cages are maintained as control

1000 9.0 500 ' 9U 250 9.0 100 ALIGN! 9.0 50 8.0 1000 “9.0 -500 9.0 250 9.0 100 ALIGN! • i: 9.0 ·· · .. íooo  9.0 500 9.0 250 ; ·· 9.0 1000 · 9.0 500 · · · ··· 9.0 250 9.0 100 ALIGN! 9.0 50 9.0.

and the two cages are. DDT as a standard preparation. Mortality is calculated 24 hours after spraying. Any flies that do not fly or cage from the bottom count as dying. The same scale as for the previous test is used for evaluation.

The compounds used, the amounts used and the test results are shown in the following table. Where more than one test has been performed, they are listed. averages of several results.

ia5 «98

22nd

Table IX. combine · / - -:. . ppan ...... fly toxicity ^; .Λ '-home

N-Trifluoroacetyl-α-nitro-S-trifluoromethyl-o-phenylenediamine

N-Difluorochloroacetyl-S-nitro-S-trifluoro: methyl-Q-phenylenediamine

N-Trifluoroacetyl-N ² - (p-nifrobenzoyl) -4 '- trifluoromethyl-8'-nitro-o-phenylenediainin

N ¹ -trifluoroacetyl-N ² -methoxycarbonyl-4'-trifluoromethyl-6'-nitro-o-phenylenediamine

N ^1- (2,2,3,3-Trifluoroproplonyl) -N ² -methoxycarbonyl-6'-nitro-4'-trifluoromethyl-o-phenylenediamine

1000 9.0 500 9.0 250 • 9.0 100 ALIGN! 9.0 50 8.5 '500 9.0 250 9.0 100 ALIGN! 9.0 50 9.0 1000 7.5 500 7.5 250 7.5 1000 9.0 500 9.0 250 · 9.0 1Ό0 9.0 1000 9.0 500 • 9.0 250 9.0 100 ALIGN! 9.0 50 7.5

Anthonomus gr.andls (Coleoptera j '

The procedure is similar to that used for Epilachna varivestis and Prodenia eridania, except that 10 adults of Anthonomus grandis are placed on sheets of cotton that have been soaked in the test compound preparation.

The scale used is the same as for the tests above.

The compounds used, the amounts used and the results obtained are shown in the following table. Where more than one test has been performed, the results given are an average of several results.

Table X compound ppm 'toxicity on Anthono. mus graňdís

N ¹ -heptaluorobutyryl-3'-nitro-5'-trifluoromethyl-o-phenylenediamine

Nt-pentafluoroproponyl-d-nitro-S-trifluoromethyl-o-phenylenediamine

N ¹ -perfluorooctanoyl-3'-nitro-5'-trifluoromethyl-o-phenylenediamine

1000 - - ' <’-9.0 500 9.0 250 9.0 100 ··> · - 9.0 50 • 9.0 - 25 9.0 1000 9.0 500  9.0 250 9.0 100 ALIGN! 9.0 50 9.0 25. 8.5 10- 8.5 Ϊ000 9.0 500 ' 9.0 250 , 9.0 100 ALIGN! 9.0 50, 9.0, • 25 9.0

toxicity to Anthonomus grandis ’.

Í9 5B9IS

24 compound

PPm. N ¹ -trifluoroacetyl-N ² -methoxycarbonyl-4'-trifluoromethyl-6'-nitro-o-phenylenediamine

N ^1- (2,2,3,3-Tetrafluoropropionyl) -N ² -methoxycarbonyl-6'-nitro-4'-trifluoromethyl-o-phenylenediamine

Almost the same results are obtained when the following compounds are used in the same way instead of the compounds listed in the table:

N ¹ -trifluoroacetyl-N ² -naphthyl-3'-nitro-5'-trifluoromethyl-ofenylenediamine,. NMrifluoroacetyl-N ² - (p-butoxy) enzoyl-4'-trifluoromethyl-6'-nitro-o-phenylenedlamine,

NMrifluoroacetyl-N ² - (p-nl trobenzoyl) -4-trifluoromethyl-6'-nitro-o-phenylenediainine,

NMieptafluorobutyryl-SMitro-SMrlfluoromethyl-o-phenylenediamine,

N-pentafluoropropanol-3'-nitro-5'-trifluoromethyl-o-phenylenediamine,

N ¹ -fluoroacetyl-N ² -methoxycarbonyl-4'-trifluoromethyl-6'-nitro-phenylenediamine,

Nt-pentadecafluorooctanoyl-S-nitro-trifluoromethyl-o-phenylenediamine.

In addition, the compounds of formula II are useful as parasiticidal agents for the systemic control of insects and mites that have been ingested by animals. These compounds have the ability to penetrate viable tissues of the host animal to which one of the compounds has been administered. Insect parasites and parasites from the group of mites that consume blood or other living tissues of host organisms. In this way the compounds that have gone through the tissues eat up the skin and are so thin. It is likely that the blood serves as a carrier through which the compounds are dispersed by the host animal, but parasites such as blood-borne Cochllomyla homlnivorax are also killed by these compounds, which means that the compounds pass through other tissues as well as blood.

Some parasites, such as the vast majority of ticks, feed on living tissues of host animals during the vast majority of parasite life. Other parasites, such as Cochllomyia honoihlvorax, feed on the host tissue only at the larval stage. A third group of parasites, such as blood-sucking flies, feed on the host animal only at the adult stage. Application of the compounds of formula II to host animals kills the parasites that feed on the animal's feed tissue, regardless of the stage at which the parasites feed.

1000 9.0 500 ..... -  ....... .— _{9) 0} ...... 250 9.0 100 ALIGN! 9.0 1000 ' 8.0 500 7.0 250 7.0

All species of insect and acarid parasites that feed on the nutrient tissues of animals are killed by the compounds of formula II. Parasites that suck the blood of Animals, those who dig into and feed on animal tissue, and those who, as larvae of Gasterophilus haemorrhoidaiis, invade and feed on the natural mucosal hosts, are all equally effectively killed. For the sake of clarity, a number of specific parasites of various host animals that can be controlled using these compounds are provided. The life stage of the parasite through which the host animal is infected is indicated for each parasite.

Parasites in horses Gastrophllus Intestinalis, adults sucking blood, Stómoxys cálcitrans, adults sucking blood, Phormia reglna, adults sucking blood, Haematopinus assinl, juveniles, adults sucking blood, Cecidophyes ribls, nymphs, adults drilling into the skin, Psoroptes equi, Adults Eating Gasterophilis intestinalis, larvae migrating the digestive tract, Blissus Ieusopterus, larvae migrating the digestive tract, Gasterophilus haemorrhoidalis, larvae migrating the digestive tract, Parasiti cattle Haematobls Irritáns, adults sucking blood, Bovicola bovis, adults eating the skin, Haematopinus quadrípertusus, nymphs, adults sucking blood,

195

2B

Fly Tsetse '' adults! sucking blood, Stomoxys. calcitrans,. suckers sucking blood, Gasterqphilus intestinalis, - adults! sucking blood, Demodex bovis, adults! drilling into the skin, Bodphilus annulatus, · larvae, nymphs, adults sucking blood, O.tobius maghini, blood sucking nymphs, Amhlyomraa maculatum,  blood suckers Decmacentdr andersonl, blood suckers Amblyomma. americáiiiim, blood suckers housefly ..Callphoridae ,. larvae infecting wounds, . bedbugs Redttyiídea, sucking blood, Parasitl prasat - Haematóplnus suis, blood suckers Tunga pe.netrans, blood suckers Parasitl of sheep and goats Pediculus humartus, blood suckers Pedieilus.cápitiS, blood suckers •. Malophagus blood suckers Psořoptes. ovís, \. nymphs Gasterophyius haémorrhoidalis, larvae migrating in cavities, Thialeurodes vaporariorum, wound infestation larvae ,. . Phormla regína, wound infestation larvae, Cochliomyls macellaria, wound infestation larvae, V. Parasitl poultry > Címex lectularíus, » suckers Cuclotogaster heterdgrapha, blood suckers

Argas pervisus, nymphs, d-spirits λ sucking blood, Knemidokoptes. inutana,  skin drillers, Knemidokoptes, ·. galinae, spirits drilling into the skin, Parasiti dogs Gasterophilus íntěstihalis, blood suckers Stomoxys calcitrans, grub suckers, Cecidophyes ripis, nymphs, adult! drilling into the skin, Dfemodex canis, spirits burrowing into the roots of hair, fleas, blood suckers.

It is understood that parasites. the above do not refer to one · host; animal. Most of the parasites are able to use different hosts; although each parasite has the most advantageous host. For example, Cecidophyes ribls attack horses, pigs, mules, humans, dogs, cats, foxes, rabbits, sheep and cattle. Gasterophilus Intestinalis attacks horses, mules, cattle, pigs, canine and many other animals .; By using the compounds of formula II, parasites of the type described above, living in the host animal listed above, as well as in other host animals, are killed. For example, these compounds are effective in cats, goats, camels and zoo animals. . . -. ₍

The host animals in which these compounds are preferably used are. dogs, bovine animals, sheep or horses controlled by ticks, fleas, flies and worms.

The time, method, and amount at which the compounds effectively apply are within a wide range. A detailed explanation of how these compounds are used is given above. ,

The compounds are administered to the animals in an amount of about 1 to about 100 mg / kg. The best amount for controlling said parasites infesting said animals must be determined 'individually, but it has been found that in many cases the optimum amount is in the preferred range of about 2.5 to 50 mg / kg. The optimum amount, depending on the case, depends on such factors as the health of the animal to be treated, the susceptibility of the parasite, the cost that the animal may incur, and the degree of control required. Lower doses are safer. .at? xhhstelean animals are. less expensive and often easier to apply,

1959 $$ π.

! ’*’ · * But provide incomplete. or minimal control of the parasites so that a new infection can occur, on the other hand, higher doses provide more complete control of the parasites, but they are more expensive and may cause discomfort in the treated animals. '

The compounds of formula II are effective when administered at any time of the year and at any age of the animal · These compounds can be administered continuously to the animals as a constant ingredient in the feed, ensuring that all parasites that come into contact with the treated animals are killed . This method of administration is by no means 'economical' and it is usually best to apply the compounds at a time when the use of the compounds can achieve the best parasite control. · Certain parasites such as cattle worms, which are horse larvae, have an active period when they attack cattle. Although these parasites are of prime importance, the compounds can only be used at this time to ensure a one-year control of the parasites. Other parasites, such as ticks, infect and attack animals throughout the year. Controls of these parasites can also be achieved. a relatively short application time such that the compounds are administered to all animals in the farm, all around, in a relatively short time, such as a few weeks. All parasites of one generation will be killed and the animals will remain free of parasites for a long time until there is a new infection with imported animals.

The compounds of formula (II) may be administered by any oral or dermal application, it being noted that many. the compounds change through the passage of the stomach - ruminant. Therefore, oral administration to ruminants is dependent only on whether the compounds are protected against the action of the stomach of the ruminant by special treatment. These modifications to suitable preparations are given below.

The repair and administration of biologically active compounds to animals varies depending on the species. the age and manner. Some formulations of the preparations and methods of application are disclosed which illustrate the practical use of these compounds for the control of parasites. The cutaneous application of the compounds of formula II can be carried out in a manner 'commonly' used in veterinary practice. Preferably, the water-soluble salts of the compounds of formula (II) are used so that no preparation is required. Alternatively, if the use of water-insoluble compounds is desired, it is preferable to dissolve these compounds in a physiologically acceptable solvent such as polyethylene glycols. It is also practical to use injectable suspensions of the compounds in the form of a fine powder suspended in a preparation of a physiologically acceptable non-solvent, a surfactant and a suspending agent.

The non-solvent may be. for example, an edible oil, such as peanut oil, globe oil, or sesame oil, the glycerol is a polyglycol glycol. or water, depending on the compound selected. <.

Physiologically acceptable additives are necessary to keep the compounds of formula II suspended. condition. These additives are selected from emulsifiers such as dodecyltoenzene sulfonate and toluenesulfonate salts, ethylene oxide / alkylphenol compound addition and oleate esters. laurate, and dispersing agents such as salts of naphthalene sulfonate, lignin sulfonate, and fatty alcohol sulfates. Thickeners such as carboxymethylcellulose, polyvinylpyrrolldone, gelatin and alginates may be used as additives for injectable suspensions. Many surfactant groups can be used to suspend the compounds. reagents, including those mentioned above. Useful surfactants are, for example, lecithin and polyoxyethylene sorbitan esters. _

The cutaneous application is preferably performed subcutaneously, intra-muscularly and also intravenously in the form of injectable preparations. Suitable needle-type and non-needle-type injection devices are used. It is also possible to use a preparation with a delayed or. with prolonged permeation of the compounds of formula II into animal tissues. For example, highly insoluble compounds can be used. In this case, the moderate solubility of the compounds results in prolonged action in that the body fluids of the animal can dissolve only small amounts of the compound at a certain time.

The prolonged action of the compounds of formula (II) can be obtained by treating the compound to a factor which physically inhibits dissolution. The preparation thus prepared is injected into the body, where it remains as a bearing from which it is drawn. Cenin slowly dissolves. Formulation forms of this type are known and consist of waxy, semi-solid substances, such as vegetable waxes and high molecular weight polyethylene glycols. . · '

An even more effective prolonged effect is obtained when animals are administered an implant containing one of the compounds of Formula II, such implants are known in veterinary practice and are usually prepared from silicone-containing rubber. The compounds are dispersed in the solid rubber implant or contained in the implant opening. When selecting a compound, it is necessary to proceed to be soluble in the rubber, since the compound first dissolves in the rubber and then is waxed from the rubber into the body liquid of the animal. .;

The amount of compound that is released from the implant, and thus the time during which the implant is effective, is controlled with good accuracy by appropriately adjusting the concentration of the compound in the implant, the outer surface of the implant with the polymer from which it is prepared.

Application of the compounds by implants is a particularly preferred route of administration. This app is highly economical and efficient as it is

Even tsFsesrs,, ^'29; exactly the time; pa Merora Is impl-anat effective. A constant concentration of the sieve agent in the tissues of the host animal is ensured. The implant can be modified to deliver the compound to several towns and perhaps:

- nb is administered to the animals. After the implant has been inserted, there is no longer any need to treat the animals in any way.

Oral administration of the compound of formula (II) is carried out. by mixing the compound with feed or drinking water or by administering an oral dose; The dosage forms, such as enemas, tablets or.

capsule.

If the compound of formula II is to be administered orally to ruminants, it is necessary to protect the compound from the undesirable degradation effect of the ruminant process. Effective methods for coating and encapsulating drugs so that they are protected in the stomach of a ruminant mammal are now known in veterinary practice. For example, such coating materials and methods are disclosed by Grant et al., U.S. Patent No. 3897,640. Grant discloses a method for protecting compounds from the action of a ruminant human, which consists in coating the fabrics with the preparation of the propionate 3- cellulose monobutyl butyrate. Such a film may also protect the compounds of formula II. With benefit . se. tablets no! The capsules containing the compound of formula (II) are coated with a film in a coating pan, or

They are sprayed in a fluidized bed. Pills of sitlitic agent. they can - prepare,

I coated with film and then can be filled into capsules. Alternatively, a solid mixture of the compound and the film-forming agent may be prepared, comminuted and milled into small particles, each containing a compound enclosed in a matrix of the film-forming agent. The particles may be filled into capsules for oral administration or may be used in oral suspension.

j, Repair of veterinary ingredients in animal feed

Animals are well known. Typically, the compound is first converted to a masterbatch in which the compound of formula II is discarded in liquid or liquid form. solid particulate carrier. Preferably, the masterbatch may contain from about 0 to about 400 grams of compound per

0.454 kg depending on the required concentration in the feed. However, it is known that many compounds of formula II can be hydrolyzed or degraded by the feed components. These compounds are customarily formulated by treating them with a protective matrix such as gelatin prior to preparing the masterbatch. The premix is then pergated in the feed mix with a conventional mixer. The exact amount of compound and hence the premix to be added to the feed is then easily calculated from the amount that the animal consumes in the day and from the concentration of the compound in the premix,

Likewise, the amount of compound added to the drinking water of the animals is calculated taking into account the weight of the animal i and the amount it consumes per day. Most preferred is the use of water-soluble salts

Compounds of the formula. jesdfžs such. a salt is not desired, then a freeze-dried preparation of the desired compound must be prepared. The preparation may be spun in concentrated form and the suspension may be mixed with drinking water or may be a neat preparation which is then suspended in the drinking water. In any case, the compound must be in gently. powdered form and preparations; are then prepared on the same principles as injectable suspensions.

The compounds are readily formulated as tablets and capsules by conventional methods well known in the art and need not be mentioned herein. The infusions comprise a compound dissolved or dispersed in an aqueous liquid mixture. Also here, it is most advantageous to prepare an infusion by dissolving the soluble salt of the compound of the formula; Π in water. It is also almost as convenient and equally effective to use dispersion compounds as it is to use. prepare the preparations in the drinking water as mentioned above.

• Examples . listed immediately below demonstrate the effect of the compounds of formula? II in the control of a number of parasites that normally; attack economically important animals. The compounds were tested against Cochliomyia hominivof α-χ-, Phormia regina larvae, Stomoxys calcitrans, mosquitoes and Dermacentor variabills. In the case of Phormia regina and Stomoxys calcitrans it is an insect, Dermacentor variabills is representative of mites.

Stomoxys calcitrans is commonly free flying. sucking parasite; Amblyoma-ma american-um is a typical blood-sucking parasite that has a nymphal and part of the adult life-cycle associated with a host animal, usually cattle. The larvae of rtorfnia regina evolve, from eggs laid near the wounds of the host animal by free-flying insects. The larvae dig into healthy flesh around the wounds and lose part of their life cycle in it, feeding on host meat and blood. .

Stomoxys calcitrans is a parasite of horses, mules, cattle, pigs, dogs, cats, sheep, goats, rabbits and humans; Ablyomma americanum primarily attacks cattle, but also horses, mules and sheep. Phormia regina larvae attack any injured animal, but are particularly harmful to cattle, pigs, horses, mules, sheep and goats.

The following tests illustrate the effect of the compounds of formula II applied in cattle. In the vast majority of cases, the tests listed below were performed on animals artificially infected with parasites.

The calf is treated with 15 mg / kg of N ^1- (2,2-3,3-tetrafluoropropionyl) -3'nitro-5'-trifluoromethyl-o-phenylenediamine in a single subcutaneous injection. The compound is applied as a dispersion in 10% polyvinylpyrrolidone.

Adult Stomoxys calcitrans are placed in a chamber completely enclosed with a wire mesh. Two or more chambers, containing 199695

32 to 60 to 100 adults. Tomoxes, calcitrans, were placed by contacting the sheared back of the calf 24 'hours after application. Stomoxes calcitrans were eaten to the animals for the indicated period of time, then evaluated and the flies were allowed to eat for an additional period of time after treatment. ^{1 The} mortality of flies is determined by counting the living and dead after a certain time. Each group was performed separately.

The results of the detected mortality are as follows:

mortality Stomoxyš • calcitrans%

1 72 95 2 77 ' 70 96 100 ALIGN! 3 77 88 90 100 ALIGN! 4 24 85 24 95

_: When this procedure is repeated using instead of mosquitoes Stomoxys calcitrans ,. the results are as follows:

• group hours after treatment mosquito mortality in%

96, 100.

if above. said procedure repeats the use of 25mg / kg, in% polyvinylpyridone, the results are as follows:

7 _; - Group two hours after treatment. mortality

'..... 1. mosquito mosquito .2 mosquito ⁴ '3 Dermacentor. ''. Varlabills 1- (2,2,3,3-tetrafluoroproponyl) -3'-nitro-5'-trifluoromethyl-o-phenylenediamine should be tested at a dose of 10. mg / kg in sesame oil against Stonioxys calcitrans in calves Procedure

5 75 24 100 ALIGN! 48 ^: 70 · 4 168 .80

from the previous modified so that drátěné- cell is placed on the back of the calf 24 hours after administration of the compound ⁷ The result are indicated in the following table:

193695

34

Table XI Time Number Live Number Dead Dead Percentage Day 1

6 hours 20 May 24 hours 0 den 2. 6 hours 3 24 hours 0 den 3 6 hours 16 24 hours 4 den 4 6 hours 10 24 hours · ' 0 den 5 6 hours - 24 hours - _; 0 den 6 6 hours -and- 24 hours O den 7 6 hours 3 24 hours 6 den 8 6 hours 35 24 hours 15 Dec den 9 6 hours 20 May 24 hours 0 den 10; 6 hours γ _μ 40 24 hours ,.· . 40 day. 11 6 hours' w of · 40 24 hours ' - 40

20 May 50 40 100 ALIGN! 37 92 40 100 ALIGN! 24 60- 36 90 30 1 40 100 ALIGN! 40 10Ó 30 100 ALIGN! 37 - .93 34 85 5 12 25 62 10 33 40 100 ALIGN! 0 0 0 O 0 0 0 0

The tests immediately above demonstrate long-term control of insect and acarid parasites using compounds of Formula II. Application of these compounds at completely low doses kills parasts that feed on treated animals, even days after application of the compounds. It is also worth noting that the control of these parasltas. it is very complete because the total or almost total number of parasites has been destroyed.

The following procedures give representative blot results.

Phormia regina larvae are used as test organisms in bioassays. The tests are performed by administering a compound of the invention in the form of a single subcutaneous injection of calf. The calves are sampled the day after application and the larvae of Phormia regina are fed with this blood. The end of the test is the last day when 90% or more of Phormia regina larvae still die. The results are shown in the following table.

19S695

3S

Table XII.

compound solvent dose (mg / kg) effective days at 90% or greater death N ¹ - (2,2,3,3-tetrafluoro) - 10% payvinyipyrrolidone 40 25 pionyl) -3'-nitro-5'-tri- 25 18 fluoromethyl-o-phenylenediamine 15 Dec 11 '· ’ 10 5 8 6 2.5 - ' Oil of sesame. 15 Dec 2.5 5 20 May dimethylsulfoxide . 8 NMlfluorochloroacetyl-S-nitro- polyethylene glycol 15 Dec 9 . sesame oil 15 Dec . 8 -5’-trifluoromethyI-q-bitches- 10% ^; polyvinylpyrrolldone 20 May '8

lendiamine

Another in vitro test for determining the control of Stomoxys calcltrans adult parasites using compounds of Formula II is as follows. Stomoxys calcltrans adults are starved for 18 hours before being placed in petri dishes or in a flying cage and treated with a blood bait. Blood used for bait is collected from treated calves at indicated intervals after treatment. Stomoxys calcltrans mortality is determined after a certain time after the bait introduction. The percent mortality at this time is compared to the normal morality obtained in petri dishes or in cages containing blood from untreated calves (control). 1- (2,2,3,3-Tetra-fluoropropionyl) -3'-nitro-5'-trifluoromethyl-o-phenylenediamine is used in this test. The results are shown in the following table.

Table XIII dose (mg / kg) hour collection hour determination of percentage of blood mortality after treatment of mortality after contact with blood.

15 in 10% polyvinyl-1-pyrrolidone 72 72 24 5 24 22nd 22nd 89 100 ALIGN! 25 in dimethylsulfoxide 2 18 100 ALIGN! _of 24 z 24 10.0. 25 in 10% polyvinyl- 168 24 92 pyrrolidone 284 24 ⁸⁴ 40 in 10% polyvinyl- 312 24 100 ALIGN! pyrrolidone 360 24 8 &:

In the tests described above, parasites are exposed to the blood of treated animals indirectly, instead of directly, such that the parasites feed directly on the animal. Using controls, however, this test is as clear as it is. when parasites suck blood directly from the animal. The degree of protection of animals against very harmful parasites of Pthormia regina is clearly demonstrated by the test, since several days after the administration of a single dose of the compound of formula ΙΓ complete control of parasites is complete.

In addition to the herbicidal, insecticidal and parasiticidal activity, the compounds of the formula II show an anthelmitic effect.

In view of the anthelmitic effect of the compounds of formula II, the compounds of formula II can be administered to warm-blooded animals to control internal parasites, in particular intestinal tract parasites, such as JSau Haemonchus confartus. Syphacis qbvelefa and Nematosplroiďes dubiutn. The application is preferably carried out per axis and may be included in the application. the diet or the compound may be administered alone or in the form of tablets or pills for cattle. A typical good result is lost when using doses. 5 to 50 mg mg / kg for a single dose and at doses from 0.001 to 0.05% when used in the diet. In representative procedures, N ¹ -trifluoroacetyl-3'-nitro-5'-trifluoromethyl-o-phenylenediamine is added to the modified mouse food at a concentration of 0.01%. Modified food is administered to a group of four mice and unmodified food to another group of four mice serving as a control. Mice from both groups are infected with Nematospirol37

9 5 6 9 5 des dubius about seven hours after feeding. Feeding is continued for eight days, on day 9 all mice are killed and the presence or number of NemaWspiroides dubius is determined in the intestine. No larvae were observed in the modified food group, with an average of 28 larvae per mouse in the control group. The same results were obtained using other compounds of formula II.

Claims (1)

SUBJECT VYNALEZU A process for the preparation of substituted N- (2,2-difluoroalkanoyl) -o-phenylenediamines in general: R 0 is a 2,2-difluoroalkanoyl radical of formula -C 1 CF 2 -Y, wherein Y is hydrogen, chlorine, fluorine, difluoromethyl or perfluoroalkyl of ^: 1 to 6 carbon atoms, R ¹ is hydrogen, a radical of formula O-C-O-Y ¹ , wherein Y ¹ is alkyl of 1 to 4 carbon atoms, benzoyl, naphthoyl or substituted benzoyl of formula ^Z P z 'wherein each of Z' is independently halogen or nitro, Z 'is C 1 -C 4 alkyl or C 1 -C 4 alkoxy, p is 0, 1 or 2, q is 0 or 1, and the sum of p and q is 1 to 3, R ⁴ is nitro, R ⁵ is trifluoromethyl and R ⁴ and R ^s are νε mutual meta position, wherein when R ¹ is hydrogen, ortho position relative to -NH - R ¹ carries one of the groups represented by R ⁴ and R ^5, characterized in that reacting a compound of formula VIII, wherein R ¹ , R ⁴ and R ⁵ are as defined above, with an acylating agent of formula IV, O II HOC-CF 2 -Y (IV) wherein Y is as defined above, or with a hailogenide or anhydride of a compound of formula IV.