DK154069B - RODENTICID ACTIVE DIPHENYLAMINE COMPOUNDS, PROCEDURES FOR REDUCING A STOCK OF ROTS AND MOUSE AND RODENTICID TO USE THE PROCEDURE - Google Patents

Description

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The present invention relates to novel rodenticide active diphenylamine compounds having lower alkyl substituents on the amino nitrogen atom, a method for reducing a rat and mouse population, and a rodenticide agent for use in the process.

It has long been known that rats and mice need to be controlled. Rats and mice are known carriers for many diseases, of which boilspest is only the best known. When the pests are found in human habitats, they also contaminate and contaminate the areas in which they live, destroying buildings and their contents by their tunnel excavation and nesting. The animals also consume food and pollute what they do not consume. A colony of rats in a cereal can consume or destroy significant amounts of feed.

15 Many types of rodenticides have been and are being used extensively. Metallic poisons, such as arsenic and thallium compounds, are still used, but of course expose humans and utility animals to serious risks. Organic chemical poisons, of which warfarin is the best known, are widely used and have served the purpose well. However, rodents develop resistance to such poisons.

Usually rodenticides are presented to rats or mice in the form of mixtures with feed. The concentration of rodenticide in the mixture is set so that rodents consume an amount of rodenticide which is either acute or chronically fatal. It is not desirable to make the mixture so concentrated that the rodent dies immediately or fairly soon after eating. Rodents, and especially rats, are intelligent enough to understand the interrelationship between 30 feed intake and death if the time interval is very short.

Therefore, the best practice is to adjust the concentration of the rodenticide so that the rodents are poisoned during a number of feed intake of the poisoned bait.

35 In special circumstances, rodentics are sometimes mixed in drinking water or produced as "trace powder".

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you ", laid out on the paths used by the rodents. After the animals have passed through the loose poison powder, they lick their feet clean and thus devour the rodenticide.

Such tertiary diphenylamines as discussed herein have not been previously known. However, it is known that secondary diphenylamines are fungicides and insecticides. It should be noted that the prior art does not enable one skilled in the art to prepare the compounds of the present invention, as explained in further detail below. Rodenticidal diphenylamines have so far been unknown.

The novel diphenylamines of the invention have the general formula NO 2 R 2

02N - <^^^ - R1 I

in 13 CF 3 R 20 wherein R is methyl, ethyl or propyl, R 2 is chlorine or bromine, 2 R is hydrogen, chlorine or bromine, 3 is R is chlorine or bromine.

The novel diphenylamine compounds of formula I are prepared by a process in which a) an aniline compound of formula R2

R1 A NHR16 II

wherein R 16 is hydrogen, methyl, ethyl or propyl and 12 3 R, R and R are as defined above, reacted with

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a 2-halo-5-nitrobenzotrifluoride compound of formula R17

02N_ ^ -X III

C 2 3 17 where X is halogen and R is hydrogen or nitro; however, R and at least one of the substituents R 1 and R-5 are hydrogen when R is nitro; step a) obtained compound where R is hydrogen, N-alkylated, 17 c) the compound obtained at step b) where R 15 represents hydrogen is nitrated and 2 d) the compound obtained at step c) where R is hydrogen , if desired, halogenated.

The invention further provides a method of reducing a population of rats or mice, characterized in that a site frequented by the rats or mice is fed to a rodenticidal agent comprising an inert carrier and as an active agent. component a rodenticidally effective concentration of a diphenylamine compound of the above formula I.

The invention also provides a rodenticidal agent for use in the process of the present invention, which is characterized in that it contains an inert carrier and as an active ingredient from 5 to 2000 ppm of a diphenylamine compound of the above Formula I.

All of the compounds listed below will be designated diphenylamines for the sake of uniformity and clarity, although the nomenclature rules may require certain compounds to be designated differently.

35 All percentages and parts below refer to percentages and parts by weight.

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The following exemplary compounds are discussed to ensure that one skilled in the art fully understands the scope of the invention. It will be understood that the invention is in no way limited to the compounds listed.

2,6-dibromo-4-chloro-N-methyl-2 ', 41-dinitro-61-trifluoromethyl diphenylamine, 2-bromo-4-chloro-N-ethyl-2', 41-dinitro-61-trifluoro methyldiphenylamine, 2,4-dichloro-N-methyl-21,4'-dinitro-6'-trifluoro-methyldiphenylamine, 4-bromo-2-chloro-N-methyl-21,4'-dinitro-6'-trifluoromethyldiphenylamine , 2,4-dibromo-6-chloro-N-ethyl-2 ', 4'-dinitro-6' - trifluoromethyl diphenylamine, N-methyl-2,4,6-trichloro-2 ', 4'-dinitro-6' -trifluoromethyldiphenylamine, 2,4,6-trichloro-2 ', 41-dinitro-N-propyl-6'-trifluoromethyldiphenylamine, 2,6-dibromo-4-chloro-N-ethyl-2', 4'-dinitro-61-tri 20 fluorine thyldiphenylamine, 2,4-dibromo-2 ', 4 * -dinitro-N-propyl-6'-trifluoromethyldiphenylamine, 4-bromo-2-chloro-N-ethyl-21, 4' -dinitro-6 '- trifluoromethyldiphenylamine, 2-bromo-4,6-dichloro-N-ethyl-2 '', 4'-dinitro-6'-trifluoromethyldiphenylamine, N-ethyl-2,6-dibromo-4-chloro-21, 41-dinitro-6'-trifluoromethyl diphenylamine, 2-bromo-4-chloro-N-methyl-21,4'-dinitro-6'-trifluoromethyldiphenylamine, 2.4-dichloro-N-ethyl-2 ', 4 'dinitro-6'-trifluoro 2-bromo-4,6-dichloro-N-methyl-2 ', 4'-dinitro-6', 2-bromo-4,6-dichloro-N-methyl-2 ', 4'-dinitro-6' -tri fluoromethyl diphenylamine, 5

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2-bromo-4-chloro-2 ', 41-dinitro-N-propyl-6'-trifluoromethyldiphenylamine, N-propyl-4-bromo-2-chloro-2', 4'-dinitro-6'-trifluoromethyldiphenylamine , 4-Bromo-2,6-dichloro-2 ', 41-dinitro-N-propyl-61-trifluoromethyl diphenylamine, 4-bromo-2,6-dichloro-N-methyl-2', 4'-dinitro -61-trifluoromethyl diphenylamine, N-propyl-2,4-dibromo-2 ', 4'-dinitro-61-trifluoromethyldiphenylamine, 2.4-dibromo-6-chloro-2', 41-dinitro-N-propyl -6'-trifluoromethyl diphenylamine, 2,4-dibromo-21,41-dinitro-N-propyl-6'-trifluoromethyldiphenylamine, 2-chloro-N-methyl-2 ', 4'-dinitro-6'-trifluoromethyl diphenylamine, 4-chloro-N-methyl-2 ', 4'-dinitro-6'-trifluoromethyl diphenylamine, 4-bromo-2', 4'-dinitro-N-propyl-6'-trifluoromethyl-diphenylamine, and 2,4-dibromo-N-ethyl-2 ', 4'-dinitro-6,6'-bis (trifluoromethyl) diphenylamine.

The following compounds are the preferred compounds of the invention.

2,4,6-Trichloro-N-ethyl-2 ', 4'-dinitro-6'-trifluoro-methyldiphenylamine, 2.4,6-trichloro-N-methyl-2', 4'-dinitro-6'-trifluorom thyldiphenylamine, 2.4-dibromo-N-methyl-2 ', 4'-dinitro-6'-trifluoro-methyldiphenylamine, 2.4-dibromo-6-chloro-N-methyl-2', 4'-dinitro-6'-tri -fluoromethyl diphenylamine, 2,4,6-tribromo-N-methyl-2 ', 4'-dinitro-6'-trifluoromethyldiphenylamine, 2,6-dibromo-4-chloro-N-methyl-2', 4'-dinitro 6'-trifluoromethyl diphenylamine and

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4-bromo-2,6-dichloro-N-methyl-21.41-dinitro-61-tri-fluormethyldiphenylamin.

The novel compounds of formula I cannot be prepared by simple, direct methods and are therefore prepared by a multi-step process. It was to be expected that such compounds could be synthesized by the direct reaction of a substituted N-alkylaniline with 2-chloro-3,5-dinitrobenzotrifluoride. Alternatively, one would expect to be able to prepare the corresponding N-H diphenylamine and alkylate the nitrogen with alkyl iodide or a similar alkylation reagent. Indeed, it has been found that none of the methods can be carried out except for those compounds where either the 2 or 6 position is unsubstituted. For most of the compounds, one of the embodiments of the process set forth below must be used.

20 25 30 35 R7

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7 O2N-H3-Halogen + Η-N- / R6-CF3 R1 R2 O2N-C Halogen + H2N- \ R6 - 6f3 r8 r3

row M

r2 «! 2

R

o ^ rs — n— ^^> - r6 CF3 r tn

C

• H

3 I> i Λ

f iH

° 2N-i \ N ^ R6 4 '- ^ CF3 r8 4-

V

optionally product nitration - halogenation

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6 7 8 In the above formula, R, R and R have the same 12 3 meanings as R, R and R respectively. The process can be carried out using an starting aniline which carries some or all of the desired substituents from R1 to 35 in the product. The halogen substituents in the aniline ring may be added at the end of the process. The final nitration step of the above process provides the 2-nitro group of the benzotrifluoride ring of the compounds of the invention.

10 no2 R1 -halogen + H2N_-R11- '132 CF3 r ± j 15 12

no2 R

02N_ ^ V._N_ ^ -R11 H

1 1 3 '

20 CF3 R

no2 r1 o ^ mt ._____ ^ if_ ^ - s11 * 13 · ^

cf3 R

Ψ any product <- halogenation 30

The alkylation step of the above embodiment B

is sterically hindered by ortho substituents on the aniline ring. IN

11 12 13 35 accordingly, R, R and R have the same meanings as R, R and R, respectively, except that

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At least one of the substituents R and R is hydrogen.

It is preferred to use an starting aniline which lacks the halogen substituents introduced by final halogenation reactions.

5 The individual steps in the above process are not unusual in organic chemistry and are carried out in the manner that an experienced organic chemist would expect. The coupling reactions linking the aniline and benzotrifluoride rings are most easily carried out at relatively low temperatures 10 between -20 ° C and + 10 ° C in dimethylformamide in the presence of sodium hydride. Other media are similarly usable. The reactions may e.g. is carried out in alkanols, such as ethanol, in which solvents the reaction temperature may be higher, between 10 ° C and 25 ° C. Other solvents, including ketones such as acetone and methyl ethyl ketone, and some, including diethyl ether and tetrahydrofuran, are satisfactory reaction solvents.

In general, a strong base which acts as an acid binding agent is needed. As mentioned above, sodium hydride is generally the most useful base, but other bases, including inorganic bases such as sodium hydroxide and sodium carbonate, and organic tertiary amines such as pyridine and triethylamine, as well as a simple excess of the aniline starting compound, can be used.

Nitration of the benzotrifluoro ring has been carried through lightly with concentrated nitric acid in acetic acid solution at room temperature. The reaction is not an unusual nitration, and it can be carried out with other common nitrating reagents, such as a mixture of concentrated nitric acid and concentrated sulfuric acid at elevated temperatures.

No solvent is used in the nitration reactions other than the acids themselves.

N-alkylation of the diphenylamines is carried out with such reagents as a dialkyl sulfate or an alkyl halide 35 in the presence of a base. When a dialkyl sulfate is used, the preferred reaction solvent is acetone. Others

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solvents such as tetrahydrofuran, dioxane and diethyl ether are also useful, as are alkanes such as hexane and octane. Dimethylformamide is: preferred solvent for alkylations with alkyl halides, although acetone is also excellent. Other solvents as described above may be used.

The preferred bases for use in the alkylation reactions are those which have a dehydrating effect, especially sodium carbonate. However, other inorganic bases, such as the alkali metal carbonates, bicarbonates and hydroxides, can be used, as are the alkali metal hydrides.

The amount of base used depends on the reaction temperature. the lower the reaction temperature is in the alkylation step * the greater the required base excess. When the reaction temperature is about room temperature, a slight excess base should be used, such as 2 moles of base per day. mole of diphenylamine. When very high reaction temperatures such as 10 ° C are used, a large excess of base should be used, approx. 10 times.

It will be appreciated that it is important to avoid contamination of the alkylation reaction mixture with water.

In general, alkylations with dialkyl sulphates are best carried out at ca. 80 ° C, although temperatures range from approx.

25 room temperature to the reflux temperature can be used. Conditions close to room temperature, such as 20-35 ° C, are preferred for alkyl halide alkylations, but higher temperatures, up to even as high as 150 ° C, may be used.

Halogenation of aniline ring is very simple · · 30 Chlorinations are usually best carried out with elemental chlorine in acetic acid or in methylene chloride or a similar halogenated solvent. Brominations are also readily carried out with elemental bromine in an acidic medium, but such other typical brominating agents as N-bromosuccinimide 35 and dibromo isocyanuric acid are also quite effective.

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The substituted starting anilines and the starting phenyl halides are readily prepared by methods well known in the chemical literature.

The following examples illustrate the preparation of typical compounds of formula I. The products of the examples have been identified by nuclear magnetic resonance analysis, elemental microanalysis, thin layer chromatography and in some cases by mass spectrophotometry and infrared analysis.

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Example 1 2,4,6-Trichloro-N-ethyl-21,41-dinitro-61-trifluoromethyl diphenylamine.

A portion of 3.5 g of sodium hydride, prepared as an oil dispersion, is washed with petroleum ether and placed in a flask with 20 ml of anhydrous dimethylformamide. The suspension is cooled to ca. -10 ° C and the flask is covered with a nitrogen atmosphere. A solution of 8 g of N-ethyl-2,4,6-tri-20-chloro aniline in 20 ml of anhydrous dimethylformamide is added over 5 minutes and the mixture is stirred for 1 hour keeping the temperature constant. Then a solution of 8.1 g of 2-chloro-5-nitrobenzotrifluoride in 20 ml of dimethylformamide is added over 5 minutes, and the whole mixture is stirred for 6 hours while allowing the temperature to rise to room temperature. Then the mixture is poured over ice and brought to a total volume of approx. 1 liter with water.

The resulting precipitate is separated by filtration and washed with pentane to prepare 7.7 g of 2,4,6-trichloro-30-N-ethyl-4'-nitro-2'-trifluoromethyl diphenylamine. - Heat 2 g of the above intermediate with 15 ml of acetic acid until dissolved. The solution is cooled to room temperature and 5 ml of concentrated nitric acid are added dropwise over 10 minutes. Next, the reaction mixture is stirred at room temperature. After 2 days, the reaction mixture is quenched with a large amount of water and the precipitate 12

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separated by filtration and purified by column chromatography over silica gel with toluene as eluent. Evaporation of the product-containing fractions gives 0.2 g of pure 2,4,6-trichloro-N-ethyl-2 ', 4'-dinitro-61-trifluoromethyl diphenylamine 5 as oil, NMR tips at 1.23, 4, 01, 7.38, 8.55 and 8.76 ppm.

Example 2 2,4,6-Trichloro-N-methyl-2,4,4'-dinitro-6'-trifluoro methyldiphenylamine.

10 g of 2,4,6-trichloro-N-methylaniline are reacted with 11 g of 2-chloro-5-nitrobenzotrifluoride by the above procedure except that the temperature is room temperature and the reaction time is about 2 hours. 5 g of 2,4,6-trichloro-N-methyl-4'-nitro-2'-trifluoromethyl diphenylamine are recovered and nitrated by the procedure of Example 1. The process gives 2 g of pure product, m.p. 125-126 ° C.

Theoretically Found C = 37.80% 37.98% Ή = 1.57% li, 5 4% IN = 9.45% 9.52 '%

Cl - 23.96% 24, -, ® $% 25

Example 3 2,4-Dibromo-N-methyl-21,41-dinitro-61-trifluoromethyl-diphenylamine.

A portion of 27 g of 2-chloro-3,5-dinitrobenzotrifluoroide is added to 20 g of aniline and 75 ml of ethanol. After briefly stirring at room temperature, the reaction mixture is seeded with a small sample of the desired fuel limb product and a precipitate is formed immediately. The precipitate is separated by filtration and identified as 28.5 g of 2,4-dinitro-6-trifluoro-methyldiphenylamine.

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The intermediate is N-methylated in two different ways, both illustrated for clarity.

A. A portion of 3.3 g of the intermediate diphenylamine is taken up in 15 ml of dimethylformamide and 1.3 g of sodium hydride is added. The reaction mixture is stirred at room temperature and 1.5 ml of methyl iodide is added during heat generation. After 1 1/2 hours, an additional 2 ml of methyl iodide is added and the mixture is warmed slightly. After a further 2 hours, the reaction mixture is added to a large amount of cold water and the aqueous layer is decanted off. The residual oil is taken up in diethyl ether and stirred with magnesium sulfate and activated charcoal. After filtration of the solids, the solution is evaporated to dryness to give 2.4 g of dark red oil, which solidifies upon cooling. The solid is heated up with petroleum ether, cooled and filtered to give 2.4 g of N-methyl-2,4-dinitro-6-trifluoromethyl-diphenylamine, m.p. 84-86 ° C.

B. 11 g of the intermediate diphenylamine are combined with 45 ml of dioxane, 14 g of sodium carbonate and 6 ml of dimethyl sulfate 20 and stirred at reflux temperature for 24 hours. An additional 12 eels of dimefey Xsulfite and 10 g of sodium carbonate are then added, and the mixture is stirred at reflux compressor tem for another 2 hours. It is then poured into water and stirred for 4 hours. The aqueous layer is then decanted off and the residue taken up in methylene chloride and filtered. The dissolved product is identified as approx. 10 g of crude N-methyl-2,4-dinitro ~ 6-trifluoromethyl diphenylamine.

The methylene chloride solution obtained under section B is brominated without further purification by the addition of 30 excess elemental bromine. The solution is stirred and allowed to stand for 1 hour and washed with water and with sodium bicarbonate solution. The organic solution is then filtered and evaporated to dryness and the residue is recrystallized from ethanol to give 11 g of 2,4-dibromo-N-methyl-2 ', 4'-35-dinitro-6 * -trifluoromethyldiphenylamine, m.p. 110 ° C.

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Theoretically Found C = 33.70% 33.95% H = 1.62% 1.86% N = 8.42% 8.52%

Example 4 2,4-Dibromo-6-chloro-N-methyl-21,41-dinitro-61-trifluoromethyl diphenylamine.

A 2.5 g portion of the product of Example 10 3 is dissolved in 10 ml of methylene chloride and the solution is saturated with elemental gaseous chlorine. After standing for 2 hours, the solution is evaporated to dryness in vacuo and the residue is recrystallized from ethanol to give 2.1 g of product, m.p. 139-141 ° C.

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Theoretically Found C = 31.52% 31.78% H = 1.32% 1.35% N = 7.88% 8.10%

Example 5 2,4,6-Tribromo-N-methyl-21,4'-dinitro-61-trifluoromethyldiphenylamine.

A 2.5 g portion of the product of Example 3 is dissolved in 25 ml of diethyl ether and 1.5 ml of concentrated sulfuric acid. The solution is stirred at room temperature with the addition of 0.7 g of dibromo isocyanuric acid. After 30 minutes of stirring, an additional 0.7 g of dibromo isocyanuric acid and 1.5 ml of sulfuric acid are added and the addition is repeated after a further 15 minutes of stirring. Five minutes after the last addition, the reaction mixture is diluted with 50 ml of diethyl ether and filtered. The organic layer is washed three times with 10% sodium carbonate solution, dried over magnesium sulfate and evaporated to dryness. The residue is recrystallized from ethanol to give 2.4 g of 2,4,6-tribromo-N-methyl-2 ', 4'-dinitro-61-trifluoromethyl diphenylamine, m.p. 150-151 ° C.

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Theoretically Found C = 29.10% 29.02% H = 1.22% 1.06% N = 7.27% 7.29% 5

Example 6 2,4,6-Trichloro-2h, 41-dinitro-N-propyl-61-trifluoromethyldiphenylamine.

A portion of 5 g of the diphenylamine intermediate, 10 (3 is prepared in the first step of Example 3, is alkylated with propyl iodide in 80 ml of dimethylformamide in the presence of 20 g of sodium carbonate. The reaction mixture is stirred at 110 ° C for 72 hours. quench the reaction mixture with water, extraction with methylene chloride 15 and evaporate the solvent in vacuo. The residue is taken up in acetic acid and the solution is saturated with chlorine and stirred at reflux for 4 hours. The product is purified by quenching the mixture in water, extraction with methylene chloride. of the extract with sodium bicarbonate solution and then with water and finally chromatography on a silica gel column with a mixture of pentane and toluene in a ratio of 5: 1. The yield is 0.35 g of 2,4,6-trichloro-2,4,4 dinitro - N-propyl 1-6'-trifluoromethyl diphenylamine as an oily liquid.

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Theoretically Found C = 40 ° <66% 40.66% 2.35% 2.22% S - 8.89¾ 8.71% ® C3L = 22.50% 22.45% -

The utility of the present invention has been investigated by administering the compounds of formula I to rodents in laboratory experiments. The following reports on 35 typical experiments illustrate the excellent rodenticidal activity of the compounds of formula I.

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The first series of experiments to be described is performed by mixing the compounds with an animal feed on a grain basis and presenting the treated feeds to male albino rats of the Sprague-Dawley strain. The feed 5 used has the following composition:

Component_%

Corn, yellow, ground 42.3

Oats, ground 10.0 10 Wheat medium 10.0

Soybean Oil, Solvent Extracted, Shelled, 50% 18.0

Skimmed milk, dried 5.0

Corn, Distillers Dried 15 Solubles 2.5

Lucerne flour, dehydrated, 17% 2.5

Whey, whole, dried 1.0

Fish meal with Solubles 4.0 20 Animal fat, beef count 2.0

Dicalcium phosphate, feed quality 0.5

Calcium carbonate 1.0

Salt 0.3

Trace mineral premix 0.2 25

Vitamin premix 0.6

Methionine hydroxy analogue 0.1 total 100.0 Compounds of formula I are mixed with portions of the above feed in the concentrations listed below. Control rats at each trial are fed the same, untreated feed.

A treatment group of 4 or 5 rats is exposed to 35 for each quantity of treated feed and allowed unlimited feed and water. The rats are weighed individually when they die or at 17

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the end of each trial that runs for 10 days if the rats survive.

The following tables indicate the concentration of the compound in the feed in parts per day. million parts of feed (ppm), the number of days after the rats started with the treated feed where each rat dies, and the weight change, positive or negative, for each rat during the 10 day trial.

Compound of Example 1, 25 ppm.

10

Rat No. Death Day Weight Change.

1 5 -64 g 2 4 -38 g 3 3 -35 g 15 44 -53 g 5 4 -44 g

Compound of Example 2, 15 ppm.

20 Rat No. Death Day Weight Change 1 5 -43 g 2 4 -42 g 3 3 -37 g 4 3 -28 g 25 5 3 -37 g

Example 3, 100 ppm.

Rat No. Dead Day Weight change · in ng 30 16 -61 g 2 7 -76 g 3 5 -72 g 4 5 -68 g 5 5 -58 g 35

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The second series of experiments / to be described is carried out in approximately the same way except that the test animals are wild house mice (Mus musculus) and that a different feed mixture is used. In these experiments, the 5 weight change of animals was not recorded.

Compound of Example 4, 50 ppm.

Animal No. Death Day 10 in 3 2 5 3 3 4 3 5 3 15

Compound of Example 5, 50 ppm.

Animal No. Death Day 1 3 20 2 2 3 4 4 3 5 3 25 The excellent rodenticidal results obtained with the compounds are obvious from the data given.

It will be seen that the compounds are effective at very low concentrations. In addition, it is highly significant that the compounds kill the rats safely but not immediately. As explained above, a good rodenticide allows time for many or all rats or mice in a colony to devour the poisoned baits before the animals begin to die. It is evident that when used in the right concentrations, the compounds of formula I act in the desired safe but delayed manner.

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The details of the method, such as the times and places where the rodenticidal agents are applied and the carriers of the rodenticidal agents, are common to rodenticides. For the sake of clarity, however, some explanation must be given of the various ways in which the process is carried out.

The method is generally effective for the control of rats and mice. Eg. For example, such pest species as those listed below are controlled by proper application of the present invention.

House mouse (Mus musculus), brown rat (Tattus norvegicus), black rat (Rattus rattus rattus),

Alexandria rat (Rattus, i.xattus, frugivorus), 15 white-footed mice (Peromyscus leucopus), tree rat (Neotoma cinerea), and field mice (Microtus pennsylvanicus).

Those skilled in the art of rodenticides will appreciate that the present invention can also be used to control rodents other than rats and mice. Since rodents other than rats and mice are frequently useful, the control of such other rodents should not be construed as a regular part of the advantages of the present invention. However, should the control of 25 other rodents be desirable under special circumstances, the invention may be applied thereto.

The present invention effectively controls rats and mice by both acute and chronic toxicity.

As one skilled in the art will understand, proper setting of the compound of the rodenticidal agent allows the invention to decrease a population of rats and mice either by immediate poisoning of the animals or by chronic poisoning them over a number of feed intakes.

35 However, as explained, the delayed lethal effect of the compounds at issue is an important factor

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by their rodenticidal utility. The maximum benefit of the present invention is achieved by adding a rodenticidal agent to sites of rats and mice which contains a compound of the compound which is not acutely fatal in a single feed intake but contributes to a lethal effect over the course of of at least two feed intake and preferably a large number of feed intake. Accordingly, it is also preferred to add such a large amount of the rodenticidal agent that it is sufficient to allow Ί0 to allow all the members of the stock to ingest the feed twice or more.

A rat consumes from approx. 5 to approx. 50 g of feed per day. day, and a mouse consumes from ca. 1 to approx. 5 g per per day, in both cases depending on the animal's age, size and health condition. A pest specialist can determine the number of animals in a colony and can supply appropriate amounts of treated feed or other preparations to provide an effective amount to each animal.

Therefore, a preferred embodiment of the invention is a method of reducing a population of rats or mice, at which a site frequented by the rats or mice is fed a sufficient amount of a rodenticidal agent to two or more feed intakes, comprising a sufficient concentration of one of the compounds described above to be effective rodenticide after two or more feed intakes. Another preferred embodiment of the invention is the rodenticidal agent just described.

Although the invention is described using the term "feed intake", the invention is also used in the application of rodenticidal agents in the form of trace powders or drinking water preparations. It will be appreciated that such preparations are used in the same manner as preparations based on feed, with appropriate adjustments being made to accommodate the differences in the manner 21

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whereupon the rodents ingest the preparations. The concentrations of the compounds in preferred drinking water or tracer powders are effectively rodenticidal after two or more water intakes or purifications. The term "feed intake" is used herein to mean water intake and purification.

Rodenticidal agents are based on inert carriers which include feed, drinking water and finely powdered solids. Feed-based agents, which are the preferred inert carriers, can include any edible product, as rats and mice are ubiquitous. Eg. such agents may include grains, meat by-products or fats. Cereal feedstuffs which can be used in rodenticidal agents include such products as oatmeal, ground or crushed corn, soybean products, wheat and wheat by-products, waste rice and the like. All grain sizes can form the basis of such agents. Sweeteners and flavor enhancers can also be added to increase the attractiveness of the bait.

Greasy rodenticidal bait preparations are usually prepared in such inert ingredients as peanut butter, other types of nut butter, dry milk, animal fats, vegetable oils and the like. Rodenticides are also sometimes based on such animal products as bone meal and on meat products, including animal by-products.

Trace powders are composed of rodenticidal compounds dispersed in powdered solids. Virtually any powder can be used, including talc, chalk, 30 milled clays, flour, nut shell flour and the like, including powdered stone.

Rodenticidal agents in drinking water include suspensions or dispersions of the compounds. The compounds are completely water insoluble and therefore it is usually necessary to grind the compound to a fine particle size and suspend it. Suspensions are common

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used in the pharmacy and selected from the thickeners such as carboxymethyl cellulose, polyvinylpyrrolidone, gelatin and the alginates, as well as the surfactants such as lecithin, alkylphenol polyethylene oxide addition products, alkyl sulfates, naphthalenesulfonates, polybenzene sulfonates and It is sometimes also possible to use silicone antifoams, glycols, sorbitol and sugars as suspending agents.

The time when a rodenticidal agent according to the 10 'invention is applied to the site where there is a colony of rats or mice is not critical. There are no seasons when a rodent colony is particularly sensitive or relatively immune to the use of rodenticides. It is usually advantageous to first lure the colony with an untreated agent.

15 Preferably, so much of the treated agent should be administered to be sufficient to last for a period during which the members of the colony consume feed at least twice.

The concentration of the compound in agents depends on the identity of the compound selected as they have different activities, on the rate at which it is desired to reduce the stock, and also on other factors. For example, the stock can be isolated so that its sole source of feed or water is a rodenticidal agent, the concentration should of course be lower than if a variety of feed sources are available. In general, rodenticidal agents should contain concentrations of approx. 5 to approx. 2000 parts per million parts of the agent. In particular, it is preferable to use concentrations from ca. 10 to approx. 500 ppm, although it will be appreciated that amounts both above and below the indicated range will be effective and even desirable under exceptional circumstances.

It will be appreciated that additives and attractants can be successfully incorporated into rodenticidal agents 35 of the invention. Such additives as e.g. odors, sex hormones and flavors are regularly used in

DK 154069 B

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rodenticidal agents and can be successfully used in the agents of the invention and help to break down the rodent suspicion.

5 10 15 20 25 30 35

Claims (4)

1. Rodenticidically active diphenylamine compounds, characterized in that they have the general formula 5 no2 R2 1 '3 CF3 rj 10 wherein R is methyl, ethyl or propyl, R 1 is chloro or bromo, 2 R is hydrogen, chloro or bromo, and 3 R means chlorine or bromine. Compound according to claim 1, characterized in that it is 2,4,6-tribromo-N-methyl-2 ', 4'-dinitro-61-trifluoromethyl diphenylamine. A method of reducing a population of rats or mice, characterized in that a site frequented by the rats or mice is fed a rodenticidal agent comprising an inert carrier and as active ingredient a rodenticidal effective concentration of a diphenylamine compound. of formula I according to claim 1 or 2. The rodenticidal agent for use in the method of claim 3, characterized in that it contains an inert carrier and as an active ingredient from 5 to 2000 ppm of a diphenylamine compound of formula I according to claim 1 or 2.