GB2136415A - Insecticidal amine salts of benzimidazole - Google Patents

Abstract

Novel salts of certain benzimidazole compounds are useful for the control of insects and have the formula <IMAGE> wherein R<1> is bromo, chloro, -CF3, -CF2Br, or -CF2Cl; R<2> is perfluoroalkyl of C1-C3 alkyl or -CF2-CF2R<3> wherein R<3> is hydrogen or C1-C6 alkyl; R<4> is a substituted ammonium cation derived from an organic amine; and n is the valence of R<4>, the said salts having a Kow>150 in the system octanol/water.

Description

SPECIFICATION Amine salts The present invention concerns novel salts of certain benzimidazole compounds, which salts are useful for the control of insects. The novel salts are of the formula

wherein R1 is bromo, chloro, -CF3, -CF2Br, or-CF2Cl; R2 is perfluoroalkyl of C13 alkyl or -CF2F2R3 wherein R3 is hydrogen or C1-C6 alkyl; R4 is a substituted ammonium cation derived from an organic amine; and n is the valence of R4, the said salts having a Kow > 1 50 in the system octanol/water.

The present salts are prepared by conventional procedures. The benzimidazole salts of formula I are prepared by reacting a compound of the formula

wherein R1 and R2 are defined as before (1) with an organic amine, R4, which is defined as before, in the presence of an aprotic solvent: or (2) with an alkali metal hydroxide or an alkali metal carbonate, followed by reacting the alkali metal salt with an appropriate salt of the R4 organic amine, in the presence of a protic solvent; or (3) with an organic amine, R4, which is defined as before, or with an appropriate salt of the R4 organic amine, in the presence of a protic solvent; and step (2) or (3) above is further followed by drying the resulting benzimidazoline salt of the formula

wherein R1, R2, R4 and n are defined as before, and R is hydrogen or C1-C4 alkyl.

Also contemplated by the present invention is an ectoparasiticidal formulation comprising as active ingredient a benzimidazole salt of formula I, associated with one or more acceptable carriers or diluents therefore. In this formulation the amount of active ingredient of formula I preferably present is from 1 to 98% by weight.

The substituted ammonium cation derived from an organic amine, R4, is generated by protonation of a primary, secondary or tertiary organic amine or is a quarternary radical. The methods used to prepare this cation are conventional. The identity of the substituted ammonium cation is not critical so long as it confers substantial lipophilicity on the salt. The salt should have a partition coefficient in the system of n-octanol and water of Kow > 1 50.

The alkali metal hydroxide or alkali metal carbonates that are used in preparing the salts of formula I are preferably, sodium or potassium hydroxide and sodium or potassium carbonate, and more preferably sodium hydroxide.

The reaction is carried out in a suitable solvent, preferably aprotic solvents such as the ethers, e.g.

diethyl ether, and halogenated hydrocarbons, preferably methylene chloride. Protic solvents such as water and the C1-C4 alkanols can be employed; however, their use favors the conversion of the intended product into the corresponding benzimidazoline salt of formula ill above.

The two salts of formulae I and Ill can be distinguished as set forth in U.S. Patent No. 4,265,901.

The temperature at which the reaction is conducted is not critical; the reaction goes forward over a wide range of temperatures, such as from 0 to 100 C., but generally room temperature or a slight elevation over room temperature is entirely adequate. If the corresponding benzimidazoline salt of formula III is obtained it can be converted back to the desired benzimidazole salt of formula I by drying, under reduced pressure or by azeotropic distillation. Otherwise, workup of the reaction mixture to isolate the intended product is carried out in routine manner.

The following examples illustrate the preparation of representative salts of formula I and will enable those skilled in the art to practice the invention.

EXAMPLE 1 2-( 1 , 1 ,2,2-tetrafluoroethyl)-4-nitro-6-(trifluoromethyl)benzimidazole, tetra-n-butylammoniu m salt 2-( 1 , 1 ,2,2,-Tetrafluoroethyl)-4-nitro-6-(trifluoromethyl)benzimidazole (33.1 grams) was dissolved in about 200 ml. of methylene chloride and excess tetra-n-butylammonium hydroxide was added. The resulting reaction mixture was stirred for half an hour, then washed with two 50 ml. portions of water, dried over magnesium sulfate, and evaporated, yielding 50 grams of a viscous oil. IR established that the product was 3-hydroxy-2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6-(trifluoromethyl)benzimidazoline, tetra-n-butylammonium salt.The oil was then held for 2 hours at 600C. and reduced pressure (about 6 mm.) and subsequently cooled to give a solid which was identified by IR and NMR as the intended product,2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6-(trifluoromethyl)benzimidazole, tetra-n-butylammonium salt. A portion of the product was dissolved in methylene chloride and diluted with isopropyl ether and allowed to stand. In 48 hours, stout needles deposited and were separated, m.p., 90-91 OC.

Microanalysis: Calculated for C26H39F7N4O2: C, 54.54; H, 6.87; N, 9.78.

Found: C, 55.47; H, 7.16; N, 9.46.

EXAMPLE 2 2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6-(trifuloromethyl)benzimidazole, tetra-n-heptylammonium salt 2-Hydroxy-2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6-(trifluoromethyl)benzimidazoline, sodium salt (37.2 grams) in 100 ml of water was stirred while a slurry of tetra-n-heptylammonium iodide (54 grams) in 1 50 ml. of hot ethanol was added. An additional 1 50 ml. of water was added and the reaction mixture stirred for 16 hours. Methylene chloride (about 300 ml.) was then added and the layers permitted to separate. Magnesium sulfate was stirred into the methylene chloride layer and filtered and evaporated at 25 OC. to a viscous oil. IR indicated that the oil was 2-hydroxy-2-(1 ,1 ,2,2- tetrafluoroethyl)-4-nitro-6-(trifluoromethyl)benzimidazoline, tetra-n-heptylammonium salt.The oil was heated to 6O0C. for 4 hours under vacuum, then cooled, yielding a solid, the intended 2-(1 ,1 ,2,2- tetrafluoroethyl)-4-nitro-6-(trifluoromethyl)benzimidazole, tetra-n-heptylammoniu m salt, m.p. 450 C.

EXAMPLE 3 2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6-(trifuloromethyl)benzimidazoline, n-decylammonium salt 2-(1,1 ,2,2TetrnfluornethyI)-4-nitrn-6-(tnfiuornmethyI)benzimidazole (33 grams) in 200 ml. of diethyl ether was stirred while n-decylamine (1 5.8 grams in 50 ml. of diethyl ether) was added in one portion. The reaction mixture was then evaporated to dryness, yielding the intended product as a waxy solid, m.p. 92-930C.

Other salts of formula I were similarly prepared by way of the preceding examples and by making any change in solvent, temperature and the like as necessary. All salts are a 1:1 ratio unless otherwise indicated. The identity of the products was confirmed by IR and NMR.

EXAMPLE 4 2-( 1 , 1 ,2,2-tetrafluoroethyl)-4-nitro-6-(trifl uoromethyl) benzimidazole, tribenzyl am moniu m salt, m.p.

940 C.

EXAMPLE 5 2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6-(trifuloromethyl)benzimidazole, tri-n-butylammoniu m salt, a viscous oil.

EXAMPLE 6 2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6-(trifluoromethyl) benzimidazole, tetra-n-propylammoniu m salt, m.p., 130-1310C.

Microanalysis: Calculated for C22H31F7N402: C, 51.16; H, 6.05; N, 10.85.

Found: C, 50.96; H, 5.91; N, 10.96.

EXAMPLE 7 2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6-(trifluoromethyl)benzimidazole, benzyltrimethylam moniu m salt, a viscous oil.

EXAMPLE 8 2-( 1 , 1 ,2,2-tetrafluoroethyl)-4-nitro-6-(trifl uoromethyl)benzimidazole, phenethylam moniu m salt, a yellow solid.

EXAMPLE 9 2-( 1,1 ,2,2-tetrafluoroethyl)-4-nitro-6-(trifl uoromethyl)benzimidazole, di-n-hexylam moniu m salt, a viscous oil.

EXAMPLE 10 2-( 1 , 1 ,2 ,2-tetrafluoroethyl)-4-nitro-6-(trifl uoromethyl)benzimidazole, n-dodecylammoniu m salt, a viscous oil.

EXAMPLE 11 2-( 1 , 1 ,2,2-tetrafluoroethyl)-4-nitro-6-(trifluoromethyl)benzimidazole, triethylam moniu m salt, a viscous oil.

EXAMPLE 12 2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6-(trifluoromethyl)benzimidazole, tri-n-propylammonium salt, a yellow powder.

EXAMPLE 13 2-(1 ,1 ,2,2-tetrafluoroethyl)-4-nitro-6-(trifluoromethyl)benzimidazole, procaine salt, a glassy solid melting at 250C.

EXAMPLE 14 2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6-(trifluoromethyl)benzimidazole,2:1 salt with benzothene, a viscous oil.

EXAMPLE 15 2-(1 ,1 ,2,2-tetrafluoroethyl)-4-nitro-6-(trifluoromethyl)benzimidazole, levamisole salt, a viscous oil.

The salts of formula I exhibit insecticidal action and can be employed for the control of insects in a wide variety of settings. For example, the salts can be employed for the control of insects which attack piants as well as humans. The salts are particularly useful for the control of colonial insects, household insects, and those insects which attack domestic animals, such as flies, lice, mites, ticks, and fleas.

Colonial insects are generally members of the order Hymen op tera, family Formicidae (ants) and the order lsoptera, family Termitidae (termites). The present salts are especially of interest for the control of fire ants, including Solenopsis geminata, Solenopsis richteri, Solenopsis invicta, and Solenopsis xyloni.

For the control of ants, the present salt is formulated in an edible bait which is positioned near the colony to be controlled, or, in the case of infested cropland, the edible baits can be distributed uniformly across the infested land. The amount of a present salt to be employed will vary with such factors as the identity of the ant, the size and number of colonies, the mode of application, and the like. Generally, good results are obtained by application of form 1 to 1 00 grams/acre, preferably 1 to 1 0 grams/acre.

Baits containing a present salt of formula I are prepared in manners conventional for the species to be controiled. For many ant species, including fire ants, the present salt is dissolved in an oil or fat which is then distributed on a carrier to constitute the edible bait.

The salts of formula I have been evaluated as toxicants for the control of imported fire ant (Solenopsis richter). The evaluation was conducted as follows. The candidate compound of formula I was formulated by dissolving it in soybean oil, with heat if necessary. If not soluble upon heating, acetone was added and later removed by evaporation. The resulting solution was placed on defatted pregelled corn grits as carrier, 30% solution and 70% carrier, to constitute a bait suitable for ingestion by ants. Three baits were prepared for each compound, at concentrations of 0.01, 0.1 and 1.0% in the bait.

Imported fire ants were collected from the field, acclimated to laboratory conditions for a week, and then employed in the test. A group of about 40 ants was exposed to the respective bait for 24 hours, then the ants were supplied with an untreated bait of soybean oil on defatted pregelled corn grits carrier for the remainder of the two-week test period. Throughout, the ants were maintained in an environment of controlled temperature and humidity. Dead ants were removed and counted daily; cumulative percent kill and control were calculated at days 1, 4, 7 and 14 of the test period. Results were as reported in the following table, each line represents a single test, with individual figures being an average of three replicates. Multiple tests were conducted with the compounds.

TABLE I Day 1 ~ Day4 Day 7 Day 14 % Kill % Kill % Kill % Kill % Kill % Kill % Kill % Kill Compound Formulation in in in in in in in in Tested Method Treated Control Treated Control Treated Control Treated' Control Example 3 1.00 1 41 0 72 0 81 0 98 53 90 0' 97 7 99 15 100 27 0.10 1 30 0 70 11 79 13 96 49 93 0 100 6 0.01 1 3 0 42 7 44 26 88 45 6 2 90 21 99 26 100 29 Example 4 1.00 1 46 0 84 8 96 11 100 35 81 0 97 3 97 3 98 6 0.10 1 60 0 87 0 92 0 100 3 96 3 99 12 100 21 0.01 1 11 0 45 7 66 17 90 57 10 5 87 10 97 15 100 18 Example 5 1.00 2 87 0 93 3 96 3 97 67 48 0 88 28 100 51 100 0 0.10 2 83 0 97 3 97 9 97 28 38 4 76 64 88 81 97 91 97 0 0.01 2 2 0 55 3 93 3 99 6 17 0 72 56 84 83 95 100 17 3 67 3 95 13 98 40 Example 6 1.00 3 67 0 89 6 96 25 100 99 100 0 0.10 3 49 0 65 5 96 23 99 53 95 0 100 12 0.01 1 0 0 16 2 42 7 69 10 1 0 32 6 52 11 97 17 TABLE I (Continued) Day 1 Day4 Day7 Day 14 % Kill % Kill % Kill % Kill % Kill % Kill % Kill % Kill Compound Formulation in in in in in in in in Tested Method Tested Control Treated Control Treated Control Treated Control Example 7 1.00 3 86 4 91 11 93 18 100 36 65 2 90 12 97 30 100 63 97 3 100 3 0.10 3 75 0 98 9 99 15 99 27 51 0 74 52 81 85 96 100 99 11 100 14 0.01 3 7 3 93 8 94 19 96 36 33 2 71 15 87 39 98 58 26 0 97 6 99 18 100 21 Example 8 1.00 3 80 18 96 82 100 100 79 0 91 3 92 3 94 30 0.10 1 81 0 97 0 100 14 96 3 100 3 0.01 1 5 2 51 20 64 50 77 93 1 0 36 4 75 11 100 11 Example 9 1.00 1 95 3 96 9 97 18 98 61 20 0 48 7 71 43 92 86 99 3 0.10 1 89 0 100 0 41 2 76 9 91 26 98 33 87 13 100 55 0.01 1 2 0 48 17 81 37 98 94 16 0 80 42 92 56 98 76 17 21 81 75 96 96 100 100 TABLE I (Continued) Day 1 Day 4 Day 7 Day 14 % Kill % Kill % Kill % Kill % Kill % Kill % Kill % Kill Compound Formulation in in in in in in in in Tested Method Treated Control Treated Control Treated Control Treated Control Example 10 1.00 1 83 0 91 5 93 19 99 46 42 0 58 5 74 18 93 64 0.10 1 95 0 99 6 100 17 34 0 61 12 78 18 97 70 0.01 1 15 0 79 7 92 87 96 100 12 0 87 0 100 19 10 3 50 3 71 36 89 86 59 0 93 8 97 41 97 77 Example 11 1.00 3 61 0 94 8 100 18 73 0 95 10 97 16 99 26 0.10 3 74 0 95 15 99 38 99 53 87 0 96 0 97 4 99 39 0.01 3 27 0 79 5 83 14 90 23 11 0 89 28 94 31 99 48 Example 12 1.00 2 66 0 94 3 96 3 100 6 91 0 97 10 98 10 99 27 0.10 2 78 0 91 5 99 16 100 16 93 0 100 0 0.01 1 43 0 90 5 97 13 100 23 22 0 98 3 99 3 100 16 Formulation code = 1 = soluble in soybean oil at room temperature 2 = soluble in heated soybean oil 3 = acetone used to solubilize in soybean oil As noted above, the salts of formula I are useful as ectoparasiticides for the control of insects which attack domestic animals. For this purpose, the salt can be applied topically or the salt can be administered orally or by injection. The salts are preferably formulated for this use with conventional adjuvants. The amount of salt to be used is not critical and will vary with the identity of the host and the insect parasite, the severity and duration of attack and other factors. In general, good results are achieved at rates of from 1 to about 50 mg./kg. The present salts are advantageous in that when administered to warm blooded animals, they are only slowly taken up by the bloodstream; the present salts therefore provide ectoparasiticidal effect over a period of time.The same delay in being taken up by the bloodstream has the effect of minimizing any toxic action the anion might otherwise exhibit to the host.

Various of the salts of formula I were evaluated for ectoparasiticidal activity. In these tests, the candidate was formulated for administration to cattle, then administered and blood samples thereafter withdrawn daily for a period of time varying from several weeks to several months.

From the blood samples, the serum was isolated and blowfly larvae and adult houseflies were fed on the serum. For the blowfly assay, 10 ml. of serum were placed in a test tube with a wick onto which 50 blowfly larvae were placed. The covered test tube was incubated at 270C. for 24 hours, at which time efficacy of the candidate compound was determined as the percent mortality of the blowfly larvae, adjusted by normal mortality in a control, and reported according to the following rating scale:: Rating % Mortality 0 = none dead 1 = 50%dead 2 = 5175% dead 3 = 7690% dead 4 = 9199% dead 5 = 100% dead For the adult housefly test. 10 ml. of serum were employed to saturate a wick which was placed in a petri dish. Twenty-five chilled houseflies were placed in the dish which was then incubated for 24 hours at 270C. and 50% relative humidity. After the end of the twenty-four hours, the efficacy of the candidate compound of formula I was determined as the percent mortality of housefly, adjusted as for blowfly by normal mortality in a control and reported according to the same scale as above.

In addition to the blowfly larvae assay and the adult housefly assays, the blood was analyzed for the concentration of the test compound, as the corresponding 2-hydroxy-2-(l,l ,2,2-tetrafluoroethy1)-4- nitro-6-(trifluoromethyl)benzimidazoline anion of formula Ill.

The results of these evaluations are set forth in the following tables. Each set of data represents a single animal.

Compounds were formulated for injection in either (I) triacetin saturated with water or (2) benzyl alcohol, at a concentration of 200 mg./ml. or 250 mgiml., respectively; in either instance the indicated amount was as the corresponding 2-hydroxy-2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6- (trifluoromethyl)benzimidazoline anion. In each evaluation, 5 mg. as the latter anion was supplied per kg. of animal body weight.

TABLE 11 TRIACETIN FORhRULATION SUBCUTANEOUS ADMINISTRATION Compound of Example 3 Test % Efficacy % Efficacy Day PPM AHF LBF SW PPM AHF LBF SW 0 1 3.9 100 100 0 2.1 24 0 0 2 4.7 100 100 0 4.1 100 100 0 3 4.2 100 100 0 5.6 100 100 0 6 5.8 100 100 1 8.7 100 100 0 8 6.7 100 100 1 8.8 100 100 1 10 7.0 100 100 1 7.8 100 100 1 13 5.3 100 100 1 6.6 100 100 1 15 4.9 100 100 1 6.4 100 100 1 17 3.8 96 100 1 5.2 89 100 1 20 2.9 41 50 1 4.9 100 100 1 22 2.6 36 25 1 4.2 83 100 1 24 2.5 48 75 1 3.8 83 100 1 27 2.5 20 0 1 4.3 75 100 1 34 2.0 23 0 1 2.1 19 0 42 1.5 20 0 1 1.2 15 0 1 48 1.7 24 0 0 1.0 19 0 0 55 1.2 17 0 0 0.6 18 0 0 62 0.6 16 0 0 0.5 26 0 0 TABLE II (Continued) Compound of Example 8 Test % Efficacy % Efficacy Day PPM AHF LBF SW PPM AHF LBF SW 0 1 16.2 100 100 0 14.2 100 100 0 2 22.8 100 100 0 16.7 100 100 0 3 22.3 100 100 0 19.8 100 100 0 6 23.4 100 100 0 21.3 100 100 0 8 17.9 100 100 1 19.6 100 100 1 10 13.6 100 100 1 15.3 100 100 1 13 8.2 100 100 1 10.8 100 100 1 15 6.2 100 100 1 9.5 100 100 1 17 4.4 84 100 1 6.8 100 100 1 20 2.0 24 0 1 3.2 43 50 1 22 1.2 19 0 1 2.3 18 0 1 24 0.7 20 0 1 1.9 15 0 1 27 0.4 24 0 1 1.7 22 0 1 34 0.1 15 0 1 0.3 15 0 1 42 NDR 21 0 1 0.1 20 0 1 48 NDR 25 0 0 0.1 24 0 0 55 NDR 16 0 0 NDR 15 0 0 62 NDR 26 0 0 NDR 25 0 0 TABLE II (Continued) Compound of Example 7 Test % Efficacy % Efficacy Day PPM AHF LBF SW PPM AHF LBF SW 0 1 18.7 100 100 0 16.9 100 100 0 2 18.1 100 100 0 19.1 100 100 0 3 18.7 100 100 0 17.7 100 100 0 6 12.2 100 100 0 13.5 100 100 1 8 12.2 100 100 1 13.6 100 100 1 10 10.5 100 100 1 10.9 100 100 1 13 7.5 100 100 1 8.7 100 100 1 15 5.1 100 100 1 6.6 100 100 1 17 3.8 88 100 1 3.9 84 100 1 20 2.4 27 0 1 2.5 36 25 1 22 2.2 16 0 1 1.8 19 0 1 24 1.8 20 0 1 1.4 23 0 1 27 1.4 21 0 1 0.9 25 0 1 34 0.4 18 0 1 0.3 25 0 1 42 0.2 19 0 1 0.1 15 0 1 48 0.1 15 0 0 0.1 29 0 0 55 NDR 16 0 0 NDR 25 0 0 62 NDR 16 0 0 NDR 20 0 0 TABLE II (Continued) Compound of Example 11 Test % Efficacy % Efficacy Day PPM AHF LBF SW PPM AHF LBF SW 0 1 27.8 100 100 0 34.1 100 100 0 2 31.0 100 100 0 31.9 100 100 0 3 28.5 100 100 0 29.0 100 100 0 6 17.4 100 100 0 17.8 100 100 0 8 15.1 100 100 1 14.5 100 100 1 10 11.5 100 100 1 10.8 100 100 1 13 6.6 100 100 1 6.5 100 100 1 15 5.1 100 100 1 4.2 100 100 1 17 3.8 96 100 1 3.0 84 100 1 20 2.3 29 25 1 1.2 21 0 1 22 1.6 15 0 1 0.7 22 0 1 24 1.0 16 0 1 0.4 15 0 1 27 0.5 24 0 1 0.2 20 0 1 34 0.2 17 0 1 0.1 21 0 1 42 NDR 20 0 1 NDR 25 0 1.

48 NDR 21 0 0 NDR 24 0 0 55 NDR 21 0 0 NDR 20 0 0 TABLE 11 (Continued) Compound of Example 10 Test % Efficacy % Efficacy Day PPM AHF LBF SW PPM AHF LBF SW 0 1 3.3 100 100 0 2.0 20 0 0 2 4.8 100 100 0 2.9 100 100 0 3 5.9 100 100 0 3.3 100 100 0 6 5.9 100 100 0 4.7 100 100 1 8 5.7 100 100 1 5.3 100 100 1 10 6.3 100 100 1 5.8 100 100 1 13 4.9 100 100 1 4.1 100 100 1 15 4.4 100 100 1 3.2 100 100 1 17 4.2 96 100 1 2.7 75 100 1 20 2.3 24 25 1 2.8 27 0 1 22 2.3 35 25 1 2.0 16 0 1 24 1.9 50 75 1 2.1 20 0 1 27 2.3 32 50 1 1.7 24 0 1 34 1.0 20 0 1 1.2 19 0 1 42 1.0 25 0 1 1.0 16 0 1 48 0.9 15 0 0 0.7 24 0 0 55 0.8 23 0 0 0.7 27 0 0 62 0.6 23 0 0 0.6 16 0 0 69 0.7 0.8 NDR = no detectable residue (0.05 ppm) SW = swelling score, on scale of 0--4, with 0 = no swelling and 4 = swelling approximately the size of a baseball TABLE Ill FORMULATION IN BENZYL ALCOHOL INTRAMUSCULAR ADMINISTRATION Compound of Example 2 Test % Efficacy % Efficacy Day PPM AHF LBF SW PPM AHF LBF SW 0 1.0 20 0 0.2 20 0 0 1 0.3 16 0 0 0.2 19 0 0 2 0.3 19 0 0 0.2 17 0 0 3 0.2 19 0 0 0.2 17 0 0 4 0.2 19 0 0 0.2 20 0 0 5 NDR 19 0 0 NDR 20 0 0 6 0.1 19 0 0 0.1 20 0 0 7 0.2 19 0 0 0.1 20 0 0 8 0.2 19 0 0 0.2 16 0 0 9 0.2 19 0 0 0.1 20 0 0 10 0.2 19 0 0 0.1 20 0 0 11 0.2 15 0 0 0.1 23 0 0 12 0.2 15 0 0 0.1 23 0 0 13 0.2 16 0 0 0.2 15 0 0 TABLEIII (Continued) Compound of Example 5 Test % Efficacy % Efficacy Day PPM AHF LBF SW PPM AHF LBF SW 0 0.5 14 0 0 0.1 20 0 0 1 8.3 100 100 0 15.8 100 100 0 2 6.0 100 100 0 13.0 100 100 0 3 4.0 100 100 0 12.4 100 100 0 4 3.2 100 100 0 8.9 100 100 0 5 3.6 100 100 0 6.0 100 100 0 6 3.5 100 100 0 7.8 100 100 0 7 2.9 100 100 0 6.5 100 100 0 8 2.9 81 100 0 5.0 100 100 0 9 2.4 85 100 0 4.7 100 100 0 10 2.4 100 100 0 3.6 100 100 0 11 2.3 24 50 0 4.2 100 100 0 12 2.2 19 0 0 2.5 100 100 0 13 2.4 20 0 0 3.5 50 75 0 14 2.6 48 75 0 16 2.1 16 0 0 19 1.6 20 0 0 TABLE III (Continued) Compound of Example 4 Test % Efficacy % Efficacy Day PPM AHF LBF SW PPM AHF LBF SW O NDR 10 0 0 0.1 20 0 0 1 23.7 100 100 0 23.7, 100 100 0 2 12.0 100 100 0 22.3 100 100 0 3 7.9 100 100 0 20.6 100 100 0 4 4.7 100 100 0 17.8 100 100 0 5 3.2 100 100 0 18.0 100 100 0 6 3.2 100 100 0 12.1 100 100 0 7 2.3 25 0 0 9.9 100 100 0 8 2.0 24 0 0 6.0 100 100 0 9 1.5 20 0 0 4.7 81 100 0 10 1.5 20 0 0 3.3 38 50 0 11 1.3 16 0 0 2.4 20 0 0 12 1.0 19 0 0 2.0 16 0 0 13 1.0 16 0 0 1.3 20 0 0 TABLE IV FORMULATION IN BENZYL ALCOHOL SUBCUTANEOUS ADMINISTRATION Compound of Example 3 Test % Efficacy %Efficacy %Efficacy Day PPM AHF LBF SW PPM AHF LBF SW PPM AHF LBF SW 0 1.0 20 0 0 1.4 16 0 0 NDR 19 0 0 1 15S 100 100 0 4.3 100 100 0 6.0 100 100 0 2 6.7 100 100 0 9.4 100 100 0 17.0 100 100 0 3 6.4 100 100 0 9.4 100 100 0 14.9 100 100 0 4 5.8 100 100 0 9.3 100 100 0 11.0 100 100 0 5 6.1 100 100 0 9.6 100 100 0 8.4 100 100 0 7 6.4 100 100 0 10.6 100 100 0 8.6 100 100 0 9 5.8 100 100 0 9.7 100 100 1 8.1 100 100 0 12 5.5 100 100 0 7.5 100 100 1 5.9 100 100 1 14 5.6 100 100 1 7.3 100 100 1 4.4 100 100 1 16 5.3 100 100 1 5.8 100 100 1 4.3 100 100 0 19 4.1 100 100 1 4.8 100 100 1 2.5 14 25 0 21 4.0 100 100 1 3.7 100 100 1 1.5 20 0 0 23 3.5 100 100 1 3.3 83 100 1 1.2 19 0 0 26 3.4 100 100 1 1.8 20 0 2 1 28 3.1 73 100 1 1.6 15 0 2 36 2.8 84 100 1 0.9 15 0 2 0.2 23 0 1 50 0.8 33 0 1 0.4 21 0 1 .0.3 20 0 0 TABLE IV (Continued) Compound of Example 9 Test % Efficacy % Efficacy % Efficacy Day PPM AHF LBF SW PPM AHF LBF SW PPM AHF LBF SW 0 . 0.8 15 0 0 NDR 20 0 0.4 25 0 0 1 6.8 100 100 0 2.6 83 100 0 1.8 24 0 0 2 6.7 100 100 0 8.3 100 100 0 3.9 89 100 0 3 6.4 100 100 0 8.6 100 100 0 5.5 100 100 0 4 3.0 100 100 0 7.5 100 100 0 5.6 85 100 0 5 2.9 100 100 0 7.1 100 100 0 5.4 96 100 0 7 2.9 96 100 0 5.1 88 100 0 4.4 89 100 0 9 2.5 52 75 1 5.3 100 100 0 3.5 100 100 0 12 2.1 35 50 1 4.6 100 100 0 2.2 50 75 1 14 2.4 32 25 1 4.1 100 100 0 2.1 38 50 1 16 2.0 14 0 1 3.4 100 100 0 1.9 25 0 1 19 1.9 20 0 1 2.3 14 0 0 1.7 9 0 1 21 1.9 14 0 0 1.9 9 0 0 1.6 15 0 0 23 2.0 16 0 0 1.5 17 0 0 1.8 20 0 0 26 28 36 1.7 16 0 1 0.7 15 0 0 1.8 20 0 1 50 0.9 21 0 0 0.3 19 0 0 1.1 16 0 0 TABLEV FORMULATION IN BENZYL ALCOHOL SUBCUTANEOUS ADMIN!STRATION Compound of Example 2 Test % Efficacy % Efficacy Day PPM AHF LBF SW PPM AHF LBF SW O NDR 16 0 0 NDR 16 0 0 1 0.1 14 0 0 0.1 20 0 0 2 0.1 14 0 0 0.1 20 0 0 3 0.1 16 0 0 NDR 14 0 0 4 0.1 14 0 0 0.1 20 0 0 5 0.1 19 0 0 0.1 14 0 0 6 NDR 19 0 0 NDR 20 0 0 7 NDR 19 0 0 NDR 20 0 0 8 0 0 10 13 15 0 17 20 TABLE V (Continued) Compound of Example 4 Test % Efficacy % Efficacy Day PPM AHF LBF SW PPM AHF LBF SW O NDR 16 0 0 NDR 16 0 0 1 23.7 100 100 0 25.9 100 100 0 2 16.5 100 100 0 17.7 100 100 0 3 15.0 100 100 0 10.6 100 100 0 4 10.3 100 100 0 5.1 100 100 0 5 5.2 100 100 0 2.4 100 100 0 6 5.7 100 100 0 1.0 100 100 0 7 4.0 100 100 0 0.4 20 0 0 8 3.1 79 100 0 0 10 2.0 20 0 0 0 13 0.6 16 0 0 0 15 0 0 TABLE V (Continued) Compound of Example 5 Test % Efficacy % Efficacy Day PPM AHF LBF SW PPM AHF LBF SW O NDR 16 0 0 NDR 16 0 0 1 12.5 100 100 0 13.6 100 100 0 2 10.3 100 100 0 9.5 100 100 0 3 8.5 100 100 0 10.3 100 100 0 4 7.6 100 100 0 12.3 100 100 0 5 7.0 100 100 0 11.0 100 100 0 6 7.1 100 100 0 10.8 100 100 0 7 5.9 100 100 0 10.0 100 100 0 8 5.2 81 100 0 7.3 84 100 0 10 3.7 100 100 0 7.2 100 100 0 13 1.3 16 0 0 4.1 77 100 0 15 3.0 86 100 0 17 2.2 15 50 0 20 1.1 20 0 0 TABLE V (Continued) Compound of Example 6 Test % Efficacy % Efficacy Day PPM AHF LBF SW PPM AHF LBF SW 0 1.0 0.6 1 2.6 100 100 0 10.7 100 100 0 2 14.9 100 100 0 13.0 100 100 0 3 13.3 100 100 0 13.0 100 100 0 4 11.8 100 100 0 10.9 100 100 0 5 12.4 100 100 0 10.7 100 100 0 6 9.8 100 100 0 7.7 100 100 0 7 100 100 0 100 100 0 8 100 100 0 100 100 0 TABLE VI FORMULATION IN TRIACETIN SUBCUTANEOUS ADMINISTRATION Compound of Example 8 Test %Efficacy %Efficacy %Efficacy %Efficacy Day PPM AHF LBF SW PPM AHF LBF SW PPM AHF LBF SW PPM AHF LBF SW 0 1 5.3 100 100 0 6.1 100 100 0 20.5 100 100 0 19.1 100 100 0 2 6.9 100 100 0 6.2 100 100 15.4 100 100 16.3 100 100 0 3 6.6 100 100 0 5.7 100 100 11.1 100 100 10.5 100 100 0 4 5.6 100 100 0 4.4 100 100 0 8.6 100 100 0 7.8 100 100 0 6 4.7 100 100 1 3.5 84 100 1 4.5 100 100 1 3.5 81 100 1 8 3.9 76 100 1 1.0 20 0 1 1.4 15 0 1 1.9 20 0 1 11 2.1 20 0 1 1.1 15 0 1 0.6 23 0 1 0.7 24 0 1 13 1.9 0.8 0.3 0.5 TABLEVI (Continued) Compound of Example 11 Test %Efficacy %Efficacy %Efficacy %Efficacy Day PPM AHF LBF SW PPM AHF LBF SW PPM AHF LBF SW PPM AHF LBF SW 0 1 9.4 100 100 0 11.6 100 100 0 18.3 100 100 0 17.8 100 100 0 2 8.0 100 100 0 11.8 100 100 0 12.1 100 100 0 9.7 100 100 0 3 7.2 100 100 0 7.8 100 100 0 8.0 100 100 0 4.8 100 100 0 4 4.6 100 100 0 5.2 100 100 0 6.4 100 100 0 3.0 79 100 0 6 2.2 38 50 1 2.2 50 75 1 2.5 48 75 1 0.9 24 0 1 8 1.3 25 0 1 1.1 20 0 1 1.1 15 0 1 0.6 19 0 1 11 0.8 18 0 1 0.4 20 0 1 0.4 21 0 1 0.1 25 0 1 13 1.0 0.4 0.3 0.0 TABLE VI FORMULATION IN TRIACETIN SUBCUTANEOUS ADMINISTRATION Compound of Example 8 Test %Efficacy %Efficacy %Efficacy %Efficacy %Eficary Day PPM AHF LBF SW PPM AHF LBF SW PPM AHF LBF SW PPM AHF LBF SW PPM AHF LBF SW 0 NOR NOR NOR NOR NOR 1 100 100 100 100 100 100 100 100 100 100 Temp: 105.6 2 100 100 100 100 100 100 100 100 100 100 Temp: 104.5 Temp: 105.5 3 100 100 100 100 100 100 100 100 100 100 Temp: 103.2 Temp: 104.8 4 16.1 100 100 7.1 100 100 8.7 100 100 21.0 100 100 9.0 100 100 Temp: 104.5 5 100 100 100 100 100 100 100 100 100 100 6 100 100 100 100 100 100 100 100 7 100 100 100 100 100 100 100 100 100 100 8 75 100 84 100 50 75 76 100 52 75 11 24 0 25 0 30 0 89 100 29 0 13 16 0 15 0 14 0 20 0 19 0 14 24 0 19 0 16 0 18 0 27 0 17 16 0 15 0 25 0 20 0 23 0 20 20 0 10 0 23 0 27 0 24 0 22 24 0 19 0 29 0 30 0 35 0 26 28 0 28 0 29 0 21 0 28 0 40 24 0 0 15 0 0 30 0 0 19 0 0 19 0 0 49 24 0 0 18 0 0 19 0 0 16 0 0 21 0 0 TABLEVII (Continued) Compound of Example 15 Test %Efficacy %Efficacy %Efficacy %Efficacy %Eficary Day PPM AHF LBF SW PPM AHF LBF SW PPM AHF LBF SW PPM AHF LBF SW PPM AHF LBF SW 0 NOR NOR NOR NOR NOR 1 100 100 100 100 100 100 100 100 100 100 2 100 100 100 100 100 100 100 100 100 100 Temp: 105.2 100 100 100 100 3 100 100 100 100 100 100 100 100 100 100 Temp: 103.9 100 100 100 100 4 12.8 100 100 17.8 100 100 7.9 100 100 7.2 100 100 12.1 100 100 5 100 100 100 100 100 100 100 100 100 100 6 100 100 100 100 100 100 100 100 100 100 7 100 100 100 100 100 100 100 100 100 100 8 85 100 88 100 89 100 20 0 89 100 11 84 100 83 100 32 0 23 0 84 100 13 43 25 47 50 24 0 25 0 29 0 14 23 0 20 0 15 0 20 0 23 0 17 27 0 15 0 26 0 20 0 15 0 20 18 0 15 0 24 0 19 0 18 0 22 16 0 24 0 19 0 29 0 32 0 26 25 0 24 0 15 0 19 0 28 0 40 24 0 0 23 0 0 16 0 0 16 0 0 19 0 0 49 16 0 0 15 0 0 20 0 0 18 0 0 16 0 0 TABLE VII (Continued) Compound of Example 12 Test %Efficacy %Efficacy %Efficacy %Efficacy %Eficary Day PPM AHF LBF SW PPM AHF LBF SW PPM AHF LBF SW PPM AHF LBF SW PPM AHF LBF SW 0 NOR NOR NOR NOR NOR 1 100 100 100 100 100 100 100 100 100 100 2 100 100 100 100 100 100 100 100 100 100 3 100 100 100 100 15.0 100 100 18.7 100 100 22.0 100 100 4 100 100 100 100 100 100 100 100 100 100 5 100 100 100 100 100 100 100 100 100 100 6 100 100 100 100 100 100 100 100 100 100 7 100 100 100 100 100 100 100 100 100 100 8 85 100 89 100 89 100 83 100 82 100 11 81 100 82 100 24 0 19 0 84 100 13 84 100 41 0 20 0 19 0 33 25 14 75 100 23 0 1 15 0 1 23 0 1 28 0 17 36 25 1 24 0 1 27 0 0 19 0 1 23 0 20 19 0 1 16 0 1 21 0 0 16 0 1 16 0 22 20 0 1 24 0 0 19 0 1 22 0 1 24 0 26 29 0 1 29 0 1 18 0 1 30 0 0 15 0 40 16 0 1 28 0 0 16 0 0 15 0 0 16 0 0 49 19 0 0 25 0 0 20 0 0 16 0 0 21 0 0 TABLE VII (Continued) Compound of Example 14 Test %Efficacy %Efficacy %Efficacy %Efficacy %Eficary Day PPM AHF LBF SW PPM AHF LBF SW PPM AHF LBF SW PPM AHF LBF SW PPM AHF LBF SW 0 NOR NOR NOR NOR NOR 1 100 100 100 100 100 100 100 100 100 100 2 100 100 100 100 100 100 100 100 100 100 Temp: 106.6 3 19.3 100 100 13.1 100 100 13.8 100 100 16.6 100 100 20.2 100 100 Temp: 105.3 4 100 100 100 100 100 100 100 100 100 100 Temp: 107.3 (Died PM) 5 (Died PM) 100 100 100 100 100 100 6 100 100 100 100 100 100 7 100 100 100 100 100 100 8 84 100 84 100 88 100 11 80 100 85 100 90 10 13 15 0 32 25 83 100 14 23 0 20 0 76 100 17 20 0 15 0 21 0 20 28 0 28 0 16 0 22 28 0 15 0 25 0 26 28 0 25 0 30 0 40 23 0 0 19 0 0 16 0 0 49 18 0 0 20 0 0 15 0 0 TABLE VI FORMULATION IN TRIACETIN SUBCUTANEOUS ADMINISTRATION (Blood levels not determined) Compound of Example 11 Test %Efficacy %Efficacy %Efficacy %Efficacy %Eficary Day AHF LBF SW AHF LBF SW AHF LBF SW AHF LBF SW AHF LBF SW 0 11 0 0 14 0 0 11 0 0 5 0 0 15 0 0 1 89 100 0 84 100 0 95 100 0 81 100 0 100 100 0 2 89 100 0 90 100 0 90 100 0 95 100 0 86 100 0 3 90 100 0 89 100 0 86 100 0 95 100 0 100 100 0 4 95 100 0 89 100 0 84 100 0 89 100 0 90 100 0 5 95 100 0 80 100 0 84 100 0 89 100 0 84 100 0 6 95 100 0 88 100 0 85 100 0 86 100 0 89 100 0 7 100 100 0 100 100 0 100 100 0 89 100 0 100 100 1 9 24 0 1 89 100 0 88 100 1 100 100 1 95 100 1 13 24 0 1 89 100 0 23 0 1 63 100 1 84 100 1 16 16 0 0 83 100 1 20 0 1 24 0 1 75 100 1 19 16 0 0 85 100 1 24 0 1 20 0 1 15 0 1 21 20 0 0 38 50 0 20 0 19 0 0 20 0 1 23 16 0 0 38 25 0 20 0 0 19 0 0 16 0 1 TABLE VIII (Continued) Compound of Example 11 Test %Efficacy %Efficacy %Efficacy %Efficacy %Eficary Day AHF LBF SW AHF LBF SW AHF LBF SW AHF LBF SW AHF LBF SW 0 19 0 0 20 0 0 10 0 0 15 0 0 15 0 0 1 95 100 0 80 100 0 90 100 0 86 100 0 90 100 0 2 86 100 0 90 100 0 89 100 0 95 100 0 95 100 0 3 95 100 0 89 100 0 85 100 0 90 100 0 90 100 0 4 84 100 0 88 100 0 95 100 0 89 100 0 85 100 0 5 89 100 0 88 100 0 84 100 0 81 100 0 89 100 0 6 94 100 0 89 100 0 85 100 0 89 100 0 95 100 0 7 95 100 0 84 100 1 86 100 1 89 100 1 100 100 0 9 89 100 1 85 100 1 88 100 1 76 100 0 89 100 0 13 15 0 1 83 100 1 100 100 1 15 0 1 84 100 0 16 24 0 1 15 0 1 20 0 1 24 0 1 24 0 0 19 18 0 1 24 0 1 21 0 1 15 0 1 20 0 1 21 15 0 0 20 0 0 25 0 1 15 0 1 20 0 0 23 18 0 0 20 0 0 15 0 1 20 0 1 15 0 0 in a variation of the foregoing test procedures, the compound of Example 12 was evaluated for ectoparasiticidal activity when applied topically. In this procedure, the compound was formulated as follows: 10 grams of compound was dissolved in 10 grams of an oil and 1.5 grams of Cab-O-sil (a colloidal silica) added.Three grams of the resulting solution was spread onto a 4 cm patch of gauze, backed by tape, and placed in contact with the shaven portion of the animal's ear. This test established the systemic activity of the compound when applied dermally. The results were as set forth in the following table.

TABLE IX oil = Capmul 8210 oil = polyethylene (a mixture of propane-1, glycol 300 2,3-triol 1-octanoate and 1-decanoate esters, produced by Capital City Products) Test % Efficacy % Efficacy % Efficacy % Efficacy Day AHF LBF 5W AHF LBF SW AHF LBF SW AHF LBF SW 0 20 0 13 0 1 15 0 24 0 16 0 25 0 2 21 0 84 100 42 50 95 100 5 84 100 100 100 100 100 79 100 LT 6 38 50 95 100 100 100 75 100 LT 7 24 0 LT 79 100 78 100 76 100 LT - 8 20 0 LT 41 50 32 50 29 25 LT 9 16 0 LT 55 75 13 0 19 0 LT 12 19 0 LT 16 0 19 0 20 0 LT 13 15 0 LT 20 0 14 0 20 0 LT 14 20 0 LT 15 0 16 14 0 LT 19 0

Claims (8)

1. A benzimidazole salt of the formula

wherein R1 is bromo, chloro, -CF3,-CF2Br, or-CF2CI; R2 is perfiuoroalkyl of C1-C3 or -CF2-CF2R3 wherein R3 is hydrogen or C1-C6 alkyl; R4 is a substituted ammonium cation derived from an organic amine; and n is the valence of R4, the said salt having a Kow > 1 50 in the system octanol/water.

2. A compound of Claim 1 wherein R1 is trifluoromethyl and R2 is 1,1,2,2-tetrafluoroethyl.

3. Any one of the following compounds; 2-(1,1,2,2-tetrafluor (trifluoromethyl)benzimidazole, tetra-n-propylammonium salt; 2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6 (trifluoromethyl)benzimidazole, tetra-n-heptylammonium salt; 2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6 (trifluoromethyl)benzimidazole, n-decylammonium salt; 2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6 (trifluoromethyl)benzimidazole, tribenzylammonium salt; 2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6 (trifluoromethyl)benzimidazole, tri-n-butylammonium salt; 2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6 (trifluoromethyl)benzimidazole, benzyltrimethylammonium salt; 2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6 (trifluoromethyl)benzimidazole, phenethylammonium salt; 2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6- (trifluoromethyl)benzimidazole, di-n-hexylammonium salt; 2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6 (trifluoromethyl)benzimidazole, n-dodecylammonium salt; 2-(1,1,2,2-tetrafluoroethyl)-4-nitro-6- (trifluoromethyl)benzimidazole, triethylam monium salt; and 2-(1,1 ,2,2-tetrafluoroethyi)-4-nitro-6- (trifluoromethyl)benzimidazole, tri-n-propylammonium salt.

4. An ectoparasiticidal formulation comprising as an active ingredient a benzimidazole salt of formula I, as claimed in any one of Claims 1 to 3, associated with one or more acceptable carriers or diluents therefore.

5. A process for prepring a benzimidazole salt of the formula

wherein R1 is bromo, chloro, -CF3, -CF2Br, or -CF2Cl; R2 is perfluoroalkyl of C1-C3 or -CF2-CF2R3 wherein R3 is hydrogen or C1-C6 alkyl;R4 is a substituted ammonium cation derived from an organic amine; and n is the valence of R4, the said salt having a Kow > 1 50 in the system octanol/water, which comprises reacting a compound of the formula

wherein R1 and R2 are defined as before (1) with an organic amine, R4, which is defined as before, in the presence of an aprotic solvent; or (2) with an alkali metal hydroxide or an alkali metal carbonate, followed by reacting the alkali metal salt with an appropriate salt of the R4 organic amine, in the presence of a protic solvent; or (3) with an organic amine, R4, which is defined as before, or with an appropriate salt of the R4 organic amine, in the presence of a protic solvent; and step (2) or (3) above is further followed by drying the resulting benzimidazoline salt of the formula

wherein R1, R2, R4 and n are defined as before, and R is hydrogen or C1-C4 alkyl.

6. A benzimidazole salt of formula I substantially as hereinbefore described with reference to any one of the examples.

7. An ectoparasiticidal formulation comprising as an active ingredient a benzimidazole salt of formula I substantially as hereinbefore described.

8. A process for preparing a benzimidazole salt of formula I substantially as hereinbefore described with reference to any one of the examples.