GB1595412A - Method for control of pests attacking animals - Google Patents

Description

(54) METHOD FOR CONTROL OF PESTS ATTACKING ANIMALS (71) We, THE BOOTS COMPANY LIMITED, a British Company, of 1 Thane Road West, Nottingham, do hereby declare the invention, for which we pray that a patent may be granted to us and the method by which it is to be performed, to be particularly described in and by the following statement:- This invention relates to methods for controlling animal pests and to certain new compositions for use in pest control.

Pests that attack animals can cause a great deal of damage and result in considerable economic loss. A particular harmful group of pests are those which attack the external parts of an animal and are known at ectoparasites. They cause severe irritation and can sometimes result in the mortality of domestic animals, a term which is used in this specification to mean (a) livestock namely pigs, Equidae such as horses and ruminants such as cattle, sheep and goats and (b) pets namely cats and dogs.

One aspect of the invention is a method for controlling pests harmful to domestic animals, which comprises applying to the locus of the pest a compound of the following formula

in which n is 0 to 5, R is halo, alkyl, trihaloalkyl, cyano, alkoxy or alkoxycarbonyl, R' and R2 are each hydrogen, alkyl, alkenyl, alkynyl or acyl, and R3 and R4 are each hydrogen or alkyl; or an acid addition salt thereof. The term "locus" is used to imply that the active compounds can be applied to the pest itself or to the habitat of the pest. For example it is sometimes convenient to spray the quarters in which an animal is kept in order to eliminate the pest from the animal's surroundings. More usually the animal is treated by external application of the active compound either as a precaution against pest attack or in order to combat an infestation of pests.

It is known that imidazolidine compounds of the type I, above, in which either Rt or R2 is hydrogen and in which both R' and R2 are hydrogen, may exhibit tautomerism between the iminoimidazolidine form (formula I) and its aminoimidazoline tautomer. For convenience throughout this specification all compounds are referred to as iminoimidazolidines.

In formula I, n can be 0 to 5, more usually 0 to 3. There is preferably at least one substituent and n is often 2. If n is more than one, the values of R need not be identical so that there can be mixed substituents on the phenyl ring.

When R is halo it can be iodo, chloro. fluoro or bromo and is preferably chloro or bromo. When it is alkyl R is preferably a group containing from 1 to 4 carbon atoms, such as for example methyl, ethyl, propyl, or butyl, especially methyl. In the case when R is trihaloalkyl it is preferably trifluoromethyl and when R is alkoxy the substituent is preferably one containing 1 to 4 carbon atoms, especially methoxy. When R is alkoxycarbonyl the substituent preferably contains 2 or 3 carbon atoms and is methoxycarbonyl or ethoxycarbonyl. In an especially preferred instance there are two substituents on the phenyl ring which are in the 2and 4-positions.

The groups R' and R2 can be the same or different and when they are alkyl they preferably contain up to ten carbon atoms such as an alkyl group containing 1 to 4 carbon atoms, for example, methyl, ethyl, propyl and butyl. When R' and Ris alkenyl it preferably contains 2 to 5 carbon atoms and examples are the allyl and methylallyl radicals. When R' or R2 is alkynyl it preferably contains 2 to 5 carbon atoms such as for example prop-2-ynyl.

When R' or R2 is acyl it can be any convenient acyl group of the formula R5CO. The radical RS can be, for example, (a) an alkyl group preferably containing up to ten carbon atoms, especially from 1 to 5 carbon atoms, (b) a cycloalkyl group preferably containing 3 to 7 carbon atoms, (c) an alkoxyalkyl group preferably containing 2 to 4 carbon atoms, such as for example, methoxymethyl, (d) an alkenyl group preferably containing 2 to 5 carbon atoms, (e) an aryl group especially phenyl which can be optionally substituted with one or more, such as 1 to 3, alkyl or halo groups, for example methyl and chloro, (f) an aralkyl group especially benzyl or phenethyl optionally substituted in the phenyl ring with one or more, such as 1 to 3, alkyl or halo groups, for example methyl and chloro, and (g) a phenoxyalkyl group especially phenoxymethyl, l-phenoxyethyl or 2-phenoxyethyl, optionally substituted in the phenyl ring with one or more, such as I to 3, alkyl or halo groups, for example methyl and chloro. It is preferred that R5 is an alkyl, an alkoxyalkyl, an aryl, an aralkyl or a phenoxyalkyl group, the alkyl group being most preferred of all.

The groups R3 and R4 can be the same or different and are selected from hydrogen and alkyl groups which contain, for example, from 1 to 4 carbon atoms, such as for example methyl.

A preferred group of compounds for use in the present invention is one of the following formula

in which n is 0 to 3, R is halo or alkyl, R' and R2 are each hydrogen, alkyl, alkenyl or acyl, and R3 and R4 are each hydrogen or alkyl; or an acid addition salt thereof.

Further preferred compounds are those in which (a) R3 and R4 are hydrogen, (b) n is 1 to 3, (c) R is halo or (d) R' is hydrogen or acyl of the formula R5CO and R2 is acyl of the formula R5CO, R5 being alkyl of 1 to 10 carbon atoms. Thus especially desirable compounds for use in the invention are those of the following formula

in which n is 1 to 3, R is halo, Rl is hydrogen or acyl of the formula R5CO and R2 is acyl of the formula R5CO, R5 being alkyl of 1 to 10 carbon atoms. These acylated derivatives possess superior activity to the non-acylated compounds. Of this group of compounds the most preferred are those in which R' is hydrogen.

A specific group of compounds for use in the invention has the following structure

in which Rl and R2 are each hydrogen, acetyl or propionyl, One example of such conpounds is 1 - propionyl - 2 - (2,4 - dichlorophenylimino)imidazolidine which is of great versatility in its uses.

In most circumstances it is satisfactory to employ the free base of formula I but, if desired, the active ingredient can be in the form of an acid addition salt, in which case the acid anion is one that is physiologically acceptable to the host animal, and when reference below is made to a compound of formula I or II it is meant to include acid addition salts. Convenient salts are those derived from both inorganic and organic acids, such as for example, hydrochloric, hydrobromic, hydriodic, sulphuric, nitic, phosphoric, sulphamic, acetic, trichloroacetic, benzenesulphonic, p-toluenesulphonic and picric acids.

Some of the compounds described above are novel, notably those of the following formula

in which R' is hydrogen and R2 is RSCO, RS being alkyl of 1 or 3 to 10 carbon atoms.

When animals are attacked by parasites there can be great economic loss and, as mentioned above, the method of the invention is especially applicable to animal livestock and to the control of insect or acarid ectoparasites which attach themselves to the external parts of the animal at some stage during their life cycle (the acarid ectoparasites are arthropods of the order Acarina). For example ticks, mites, keds, lice and flies are amongst the pests which are a serious problem in the rearing of cattle, pigs and sheep. We have found that the method of the invention is particularly applicable to the control of acarid ectoparasites which attack livestock, especially cattle and pigs. Accordingly the invention includes a method for controlling acarid ectoparasites harmful to livestock which comprises applying to the locus of the pest a compound of formula I. It is often convenient to apply the active compound directly to the external parts of the animal and so a further aspect of the invention is a method for controlling ectoparasites which comprises externally applying to livestock a compound of the formula II. This method is especially effective in the treatment of cattle infested with ticks of the family Ixodidae, for example, the species Boophilus microplus, Boophilus decoloroms.

Rhipicephalus evertsi, Rhipicephalus appendiculatus, Amblyomma hebraeum and Hyalomma rufpes. Thus the invention includes a method for protecting cattle from cattle tick which comprises treating the cattle externally with a compound of formula II.

Techniques for externally treating livestock are well-known in the art, the most commonly used being the spray, dip and pour-on techniques. The animal can be sprayed with a composition containing the active ingredient by means of, for instance, a hand spray or spray race. In essence the dip method of treatment entails passing the animal through an aqueous medium containing the active compound in a conventional dip apparatus such as a cattle dip. As an alternative, the pour-on technique involves the use of smaller quantities of liquid for application along the back of an animal.

The dosage of active ingredient depends on the nature of the infestation and on the host animal. When it is the sole pesticide employed, an amount within the range of from 0.1 to 100 mg, more especially frorn 0.5 to 75 mg, per kilogram body weight of the host is often appropriate. It is often convenient to employ a spray or dip wash with a concentration of from 0.001 to 1.0 per cent, more especially from 0.005 to 0.5 per cent by weight of active ingredient. In the case of a pour-on composition for application to cattle the amount applied to the animal can vary, for instance, within the limits of from 0.1 to 10 gm, more especially from 0.5 to 5 gm, per beast.

As indicated above, a compound of formula I is preferably applied as one of the many well-known formulations employed in animal husbandry. The invention includes such pesticidal compositions for application to domestic animals which comprise a compound of formula I, optionally together with a diluent or carrier, in the form of for example a solution, an aqueous dispersion, an aqueous emulsion, a dusting powder, a dispersible powder, a fumigant, an emulsifiable concentrate or a dispersible concentrate.

In the case of animal livestock the compound of formula I can, in many instances, be employed as a spray or dip. The material is often prepared by diluting a dispersible powder or emulsifiable concentrate with water, and as a particular aspect of the invention there is included a cattle or sheep dip which comprises an active ingredient of formula I in association with a surfactant, the nature and proportion of the ingredients being such that, on dilution with an appropriate quantity of water, stable aqueous compositions are produced that are suitable for the treatment of cattle or sheep by the conventional procedures of dipping and spraying.

A dispersible powder comprises the active ingredient in finely divided form in association with a dispersing agent, the concentration of active ingredient being from, for example, 5 to 95 per cent by weight of the composition. Additional materials such as for example, a suspending or antifoaming agents may be employed and a finely divided inert solid diluent such as kaolin, precipitated silica, talc or diatomaceous earth is generally incorporated in the dispersible powder.

An emusifiable concentrate comprises an active ingredient together with an emulsifying agent and optionally dissolved in the medium of a water-immiscible solvent, the concentration of active ingredient being from, for example, 5 to 95 per cent by weight of the composition.

Surfactants such as the dispersible and emulsifying agents employed in the dispersible powder and emulsifiable concentrate can be any of those commonly used, which include for example, anionic, nonionic and cationic compounds.

Anionic compounds include for example a carboxylate such as a metal carboxylate of a long chain fatty acid; an N-acylsarcosinate; a sulphonate such as an alkylbenzenesulphonate or a petroleum sulphonate; a sulphate such as a sulphated alcohol, a sulphated natural fat or oil; or a phosphate ester such as an alkyl orthophosphate or an alkyl polyphosphate. Nonionic compounds include for example an ethoxylated alkylphenol such as a nonyl phenoxypoly(ethyleneoxy)ethanol; and ethoxylated aliphatic alcohol such as an alkylpoly(ethyleneoxy)ethanol; or a carboxylic ester solubilized with a polyol or polyoxyethylene. Examples of a cationic agent include, for instance, the aliphatic mono-, di-, or polyamine as an acetate, naphthenate or oleate; an oxygen containing amine such as amine oxide or polyoxyethylene alkylamine; an amidelinked amine prepared by the condensation of a carboxylic acid with a di- or polyamine; or a quaternary ammonium salt.

When in the form of a pour-on composition, the active ingredient can be suspended or dissolved in a variety of media including, for example, an aqueous medium, an organic solvent or an oil vehicle. When water is used as the medium it can be convenient to employ a flowable composition of finely divided particles of a solid active ingredient suspended in the aqueous medium. Alternatively it is often convenient to use an oil medium and suitable materials include oils of animal, vegetable or mineral origin, for example, sunflower seed oil, maize oil, polyethylene glycol or liquid paraffin.

As stated above the invention includes cattle or sheep dips, sprays, dispersible powders, emulsifiable concentrate and pour-on compositions and in addition the following specific compositions: (a) A cattle or sheep dip comprising 1 - propionyl - 2 - (2,4 dichlorophenylimino)imidazolidine in association with a surfactant and optionally in addition a diluent or carrier, the nature and proportion of the ingredients being such that, on dilution with an appropriate quantity of water, a stable aqueous composition is produced that is suitable for the treatment of cattle or sheep.

(b) A pesticidal composition in the form of a dispersible powder comprising I propionyl - 2 - (2,4 - dichlorophenylimino)imidazolidine in finely divided form in association with a dispersing agent, the concentration of the active ingredient being from 5 to 95 per cent by weight of the powder.

(c) A pesticidal pour-on composition comprising 1 - propionyl - 2 - (2,4 dichlorophenylimino)imidazolidine in the form of a finely divided dispersion of particles having an average diameter of from 0.1 to 20 microns in an aqueous medium, the active ingredient being present to the extent of from 2 to 60 per cent by weight.

(d) A pesticidal pour-on composition comprising 1 - propionyl - 2 - (2,4 dichlorophenylimino)imidazolidine dissolved in a medium comprising a pharmacologically acceptable oil, the active ingredient being present to the extent of from 2 to 60 per cent by weight.

Similar formulations to (a) to (d) comprising an active ingredient of formula III or a novel compound as described in any of Examples 2 to 7, are included in the invention.

In addition to its relevance in animal husbandry the method of the invention is of practical application in the treatment of cats and dogs which are subject to infestation by pests, and accordingly the invention comprises a method for controlling an infestation of pests on a cat or dog which comprises applying to the pests a compound of formula I above. Application of the active compound can be by any of the methods known for grooming pets, in order to control a wide range of pests, especially mites. Particularly convenient ways of applying the active compound are, in this instance, by means of a wash prepared from a dispersible powder or a dusting powder. The latter comprises a compound of formula I intimately mixed and ground with a solid pulverulent diluent, for exampe kaolin. An example of a pesticidal dusting powder suitable for treating a cat or dog is one that comprises 1 - propionyl - 2 - (2,4 dichlorophenylimino)imidazolidine intimately mixed with a solid pulverulent diluent, the active ingredient being present to the extent of, for example, from 1 to 50 per cent by weight of the dusting powder.

A compound of formula I may be employed in combination with other pesticides for controlling ectoparasites, if desired. Such additional pesticides include, for example, an organophosphorus compound such as tetrachlorovinphos, oxinothiophos, fenitrothion, phosalone, dioxathion, chlorfenvinphos, coumaphos, bromophos-ethyl or chlorpyrifos; a carbamate such as carbaryl or promecarb; a bridged diphenyl compound such as tedion, tetrasul, chlorbenside or DDT; a chlorinated hydrocarbon such as benzene hexachloride or toxaphene; clenpyrin; chlormethiuron; nimidane; amitraz; or a synthetic pyrethroid such as NRDC 143.

A number of methods can be used to prepare the active compounds employed in the invention, one of which comprises reacting an isothiouronium salt of the following formula

in which X can be for example iodine, with a diamine of the formula HRlNCHR3CHR4NHR2, in which n, R, R3, R4 have the meanings assigned them above, R' and R2 are hydrogen, alkyl, alkenyl or alkynyl, and R6 is an alkyl group containing I to 4 carbon atoms for example methyl or ethyl, in the optional presence of a solvent such as methanol, and at a temperature preferably within the range 50 to 2000 C. Compounds of formula IV can be prepared by a route that comprises reacting a compound of the formula

with benzoyl chloride and ammonium thiocyanate, then hydrolyzing the product of this reaction with alkali, followed by treatment with alkyl halide.

A second method of preparation comprises reacting a chloroformimidoyl chloride of the formula

with a diamine of the formula RlNHCHR3CHR4NHR', preferably in the presence of a solvent such as for example ether or benzene at a temperature of for example 0 to 25"C. In their turn, compounds of formula V can be prepared by reacting a mixture of sulphuryl chloride and thionyl chloride with a compound of the formula

A third method of preparation comprises reacting a monoacylated pyrrolidone of the formula

in which R5 has the meaning assigned to it above and R7 is alkyl, or alkenyl or alkynyl, with an arylamine of the formula

in the presence of for example phosphoryl chloride, at a temperature of from 50 to 70 C., followed by hydrolysis or reaction with a primary alcohol.

A further method for preparing compounds in which one or both Rl and R2 are alkyl or acyl, comprises reacting a compound of the formula

prepared, for example, in a manner such as described above, with the appropriate alkylating or acylating agent, for example methyl iodide, dimethyl sulphate, benzoyl chloride, acetyl chloride or acetic anhydride. This method can be modified somewhat in the case of mono-substituted compounds by first preparing a sodio-derivative, followed by reaction with the appropriate alkylating or acylating agent. Alternatively, acylated compounds can be prepared by the omission of the final hydrolysis or alcoholysis step in the third method described above.

The invention is illustrated by the following Examples.

EXAMPLE 1 A solution of 46 g 2 - (2,4 - dichlorophenylimino-imidazolidine and 28.6 g propionic anhydride in one litre of dry toluene was allowed to stand at room temperature for 24 hours. The solution was washed with aqueous sodium bicarbonate solution and then water, and dried over magnesium sulphate.

Evaporation gave the required propionyl derivative which was recrystallised from propan-2-ol to give the pure material, 1 - propionyl - 2 - (2,4 dichlorophenylimino)imidozolidine, melting point 126--128"C.

The 2 - (2,4 - dichlorophenylimino)imidazolidine employed in the above reaction was prepared as follows.

To a stirred solution of 167 g ammonium thiocyanate in one litre of acetone was rapidly added 282 g benzoyl chloride. The mixture was refluxed for five minutes and then a solution of 324 g 2,4-dichloroaniline in one litre of acetone was added gradually so as to maintain gentle reflux. When the addition was completed, the mixture was stirred and refluxed for thirty minutes before cooling and adding to iced water.

The solid benzoyl derivative was filtered off, washed with water and then suspended in four litres of 10 percent aqueous sodium hydroxide solution. The mixture was stirred and heated on the steam bath for one hour, treated with charcoal and filtered whilst hot. The cooled filtrate was acidified with hydrochloric acid and then made just alkaline with ammonium hydroxide. The resulting white solid was filtered off and dried. Recrystallisation with charcoal from ethanol gave the pure thiourea, 2,4-dichlorophenylthiourea, melting point 157--1590C.

A mixture of 193.7 g of this thiourea, 88 ml water and ill g dimethyl sulphate was stirred and warmed with a free flame until reaction started. The solution was refluxed for one hour and then evaporated. Residual traces of dimethyl sulphate were codistilled with water and then ethanol.

The residual oily liquid was dissolved in one litre of methanol and 175 ml of ethylene diamine was added dropwise with stirring. the mixture was refluxed for twenty hours, filtered, and the filtrate evaporated. The residual syrup was added to iced water and basified with aqueous sodium hydroxide solution. The resulting white solid was filtered off and dried. Recrystallisation with charcoal from ethyl acetate gave 2 - (2,4 - dichlorophenylimino)imidazolidine, melting point 151--152"C.

1 - Propionyl - 2 - (2,4 - dichlorophenylimino)imidazolidine was reacted with the appropriate acid to give the following salts: l-propionyl-2-(2,4-dichlorophenylimino)imidazolidine picrate, melting point 232--233"C.

1 -propionyl-2-(2,4-dichlorophenylimino)imidazolidine hydrochloride, melting point l9(wl920C.

EXAMPLE 2 A mixture of 11.5 g 2 - (2,4 - dichlorophenylimino)imidazolidine, 1.7 g sodium hydride (80 per cent dispersion in oil) and 80 ml dry tetrahydrofuran was stirred and refluxed for one and a half hours, and a solution of 5.9 g isobutyryl chloride in 20 ml dry tetrahydrofuran was then added dropwise. The mixture was stirred and refluxed for five hours and then cooled and poured into iced water to give a solid which was dried over phosphorus pentoxide. Recrystallisation with charcoal from ethanol gave the novel compound 1 - isobutyryl - 2 - (2,4 - dichlorophenylimino)imidazolidine, melting point 147-148 0C.

The iminoimidazolidine compound employed in the above reaction was prepared according to the method described in Example 1.

The following novel compounds were prepared by a similar method. Where the compound isolated was a syrup and could not therefore be characterised by means of a melting point or boiling point the RF value is quoted, as obtained by thin layer chromatography using Merck Kieselgel 60 PF2,4. The spots on the chromatograph were located by means of ultra violet radiation and in each instance the solvent employed is quoted in brackets. The structure was confirmed by elemental analysis.

1 -butyryl-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 141--142"C.

1 -benzoyl-2-(2,4-dichlorophenylimino)imidazolidine.

m.p. 169--1.70"C.

1 -valeryl-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 111--112"C.

1 -hexanoyl-2-(2,4-dichlorophenylimino)imidazolidine.

m.p. 103--1040C.

-allyl-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 72--73"C.

I -pivaloyl-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 129--130"C.

1 -methyl-2-(2A-dichlorophenylimino)-3-propionylimidazolidine, a syrup RF 0.6 (ethyl acetate).

I -(but-2-enyl)-2-(2,4-dichlorophenylimino)imidazolidine, a syrup, RF 0.4 (9:1 toluene and industrial methylated spirits).

I -(prop-2-ynyl)-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 59--62"C.

I -nonyl-2-(2,4-dichlorophenylimino)imidazolidine, a syrup, RF 0.5 (ethyl acetate).

1-(DL-2-methylbutyryl)-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 107--109"C.

1-heptanoyl-2-(2,4-dichlorophenylimino)imidazolidine, m.p.l l9-l2l0C.

1-p-chlorobenzoyl-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 154--1550C.

1-m-chlorobenzoyl-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 15152"C.

1-o-chlorobenzoyl-2-(2,4-dichlorophenylimino)imidazolidine, m.p. l56-l-570C.

I-octanoyl-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 95--97"C.

I -nonanoyl-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 96 980C.

1-cyclopropanecarbonyl-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 148--149"C.

- cyclobutanecarbonyl-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 136 l370C.

1 -cyclopentanecarbonyl-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 130131 C.

1-cyclohexanecarbonyl-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 135--136"C.

1-(3,4-dichlorobenzoyl)-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 175 l760C.

1-ethoxycarbonyl-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 138 l390C.

I -(2-phenoxypropionyl)-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 147--148"C.

1-p-bromobenzoyl-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 177-179 C.

1 -hexyl-2-(2,4-dichlorophenylimino)imidazolidine, a syrup, RF 0.5 (ethylacetate) 1-(2,5-dichlorobenzoyl)-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 14-146"C.

1-p-nitrobenzoyl-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 205 2060C.

1-phenylacetyl-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 170173 C.

1-pivaloylmethyl-2-(2,4-dichlorophenylimino)imidazolidine, a syrup, RF 0.4 (ethyl acetate).

1-(pent-4-enoyl)-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 97-97.5 C.

1-(3-methylbut-2-enyl)-2-(2,4-dichlorophenylimino)imidazolidine, m.p. 55--56"C.

EXAMPLE 3 A solution of 12.1 g N - 2,4 - dichlorophenylchloroformimidoyl chloride in 50 ml dry ether was added dropwise with stirring to 18.5 g N - methylethylene diamine in 75 ml dry ether at 10 to 150C Heat was evolved and an oily precipitate formed, After stirring at room temperature for one and a half hours, the mixture was poured into iced water. The mixture was extracted with ether and the combined ethereal extracts were washed with water and then dried over magnesium sulphate. Evaporation in vacuo gave a clear syrup which was dissolved in ether and ethereal hydrogen chloride was added, and the precipitated hydrochloride was dried over phosphorus pentoxide. A portion of the hydrochloride was recrystallised from methanol/ether mixture to give a product having a melting point 229-2310C.

The remainder of the hydrochloride was converted to the free base by dissolving it in water, treating the solution with charcoal and basifying with sodium hydroxide. The free base was extracted with dichloromethane and washed with water and then dried over magnesium sulphate. Evaporation gave the novel compound 1 - methyl - 2 - (2,4 - dichlorophenylimino)imidazolidine, as a colourless syrup. When the compound was subjected to thin layer chromatography on Merck Kieselgel 60PF2s4, employing ethyl acetate as solvent and observed by means of ultra violet radiation, it was found to have an RF value of 0.3. A satisfactory elemental analysis was obtained.

The N - 2,4 - dichlorophenylchloroformimidoyl chloride employed in the above method was prepared as follows. To a mixture of 67.5 g sulphuryl chloride and 150 ml thionyl chloride maintained at 15 to 200C, was added in portions 95.0 g 2,4-dichloroformanilide. When the addition was completed the suspension was stirred at room temperature for two hours, then gradually warmed to 800C over a period of two and a half hours and finally heated at 800C for half an hour. The mixture was filtered and the filtrate was evaporated in vacuo from a water bath at 50"C. Distillation of the residue gave a yellow oil, boiling point 116-1 190C/5 mm.

The following novel compound was made by a similar method, 2 - (4 chloro - 2 - trifluoromethylphenylimino)imidazolidine, m.p. 185--1870C.

EXAMPLE 4 A solution of 43.5 g of 2,3,4-trichlorophenylthiourea and 35.5 g methyl iodide in 170 ml methanol was refluxed gently for one and a half hours. The solution was evaporated and the residual methyl iodide was codistilled by addition and then evaporation of more methanol. The resulting solid was refluxed overnight with 34 ml ethylenediamine and 170 ml methanol. The solution was evaporated to give a solid which was suspended in iced water, filtered off and dried over phosphorus pentoxide to give 2 - (2,3,4-trichlorophenylimino)imidazolidine. This novel compound, recrystallised from ethyl acetate, had a melting point of 161"C.

The 2,3,4-trichlorophenylthiourea employed in the reaction above was prepared as follows. To a stirred solution of 42.0 g ammonium thiocyanate in 200 ml acetone at room temperature was added rapidly from a dropping funnel 70.3 g benzoyl chloride. The mixture was refluxed for five minutes and then a solution of 98.3 g 2,3,4 - trichloroaniline in 150 ml acetone was added gradually so as to maintain gentle reflux. A thick precipitate formed and it was necessary to add more acetone to facilitate stirring. The mixture was stirred and refluxed for thirty minutes and then poured into iced water. The benzoyl derivative was filtered off, washed with water, then suspended in 1 litre of 10 per cent sodium hydroxide solution. The mixture was stirred and heated on the steam-bath for one hour, treated with charcoal and filtered whilst hot. It was acidified with concentrated hydrochloric acid and then made just alkaline with ammonium hydroxide solution.

The solid was filtered off, dried and recrystallised with charcoal from propan-2-ol to give 2,3,4 - trichlorophenylthiourea, melting point 185--1860C.

The following novel compound was made by a similar method, 2 - (4 chloro - 2 - ethylphenylimino)imidazolidine, melting point 115--1170C.

EXAMPLE 5 A solution of 2.3 g 2 - (2,4 - dichlorophenylimino)imidazolidine and 1.1 g acetic anhydride in 50 ml dry benzene was allowed to stand at room temperature for three days. The white crystalline solid was filtered off and washed with benzene to give the novel compound I - acetyl - 2 - (2,4- dichlorophenylimino) imidazolidine, melting point 168--169"C.

The iminoimidazolidine compound employed in the above reaction was prepared according to the method described in Example 1.

The following novel compounds were made by a similar method.

I -propionyl-2-(2,4-dibromophenylimino)imidazolidine, m.p. 162--163"C.

1 -propionyl-2-(2-bromo-4-chlorophenylimino)imidazolidine, m.p. 151--152"C.

I -propionyl-2-(4-bromo-2-chlorophenylimino)imidazolidine, m.p. 134--135"C.

EXAMPLE 6 A mixture of 7 ml acetic anhydride and 2.3 g 2 - (2,4- - dichlorophenyl imino)imidazolidine was heated on the steam bath for two hours, cooled and poured into iced water. The white solid was collected and dried over phosphorus pentoxide and then recrystallised from ethanol to give the novel compound, 1,3 diacetyl - 2 - (2,4 - dichlorophenylimino)imidazolidine, melting point 113--115"C.

The iminoimidazolidine compound employed in the above reaction was prepared according to the method described in Example 1.

The following novel compound was prepared by a similar method, 1.3-dipropionyl-2-(2,4-dichlorophenylimino)imidazolidine m.p. 94--95"C.

EXAMPLE 7 A solution of 6.9 g 2 - (2,4 - dichlorophenylimino)imidazolidine and 150 ml ethyl formate was refluxed gently on the steam bath for twenty minutes. The mixture was cooled and filtered to give a white solid. Recrystallisation from propan-2-ol gave the novel compound I - formyl - 2 - (2,4 dichlorophenylimino)imidazolidine hydrate, melting point 168 l700C.

The iminoimidazolidine compound employed in the above reaction was prepared according to the method described in Example 1.

EXAMPLE 8 This Example illustrates a flowable composition comprising 1 - propionyl 2 - (2,4 - dichlorophenylimino)imidazolidine. The following ingredients were mixed together and ground in the wet state by means of a ball mill.

l-Propionyl-2-(2,4-dichlorophenylimino) imidazolidine 50.0% w/v Bentonite (colloidal hydrated aluminium silicate) 4.0% w/v Dyapol PT (a sulphonated condensate of urea cresol and formaldehyde) 5.0% w/v Aerosol OT-B (a mixture of sodium dioctyl sulphosuccinate and sodium benzoate) 0.1% w/v Antifoam M30 (a silicone-based antifoam) 0.1% w/v Water 100.0% volume Such a knowable composition can be used as a pour-on or a suitable spray or cattle dip prepared by dilution of 2.5 litres of the composition of 2500 litres of water.

EXAMPLE 9 This Example illustrates dispersible powders prepared, for example, by mixing the following ingredients 1 -Propionyl-2-(2 A-dichlorophenylimi no)- imidazolidine 50.0% w/w Polyfon F (sodium lignosulphonate) 10.Q/0 w/w Aerosol OT-B 0-5 O w/w Colloidal silicic acid 5.0% w/w Kaolin 34.5% w/w Similar dispersible powders were prepared substituting as active ingredient the following compounds, 2-(2,4-dichlorophenylimino)imidazolidine 2-(4-chloro-2-trifluorophenylimino)imidazolidine 1 ,3-diacetyl-2-(2,4-dichlorophenylimino)imidazolidine 1 -acetyl-2-(2,4-dichlorophenylimino)imidazolidine 1 ,3-dipropionyl-2-(2,4-dichlorophenylimino)imidazolidine I -benzoyl-2-(2,4-dichlorophenylimino)imidazolidine 1 -valeryl-2-(2,4-dichlorophenylimino)imidazolidine 1 -p-chlorobenzoyl-2-(2,4-dichlorophenylimino)imidazolidine l-propynyl-2-(2,4-dichlorophenylimino)imidazolidine.

EXAMPLE 10 This Example illustrates emulsifiable concentrates prepared, for example, by mixing the following ingredients to produce a solution.

1 -Methyl-2-(2,4-dichlorophenylimino)- imidazolidine 10.0% w/v Agrilan CA (calcium dodecyl benzene sulphonate with nonylphenol ethoxylates) 5.0% w/v Agrilan BA (calcium dodecyl benzene sulphonate with nonylphenol ethoxylates) 5.0% w/v Xylene to 100.0To volume Similar emulsifiable concentrates were prepared substituting as active ingredient the following compounds l -methyl-2-(2,4-dichlorophenylimino)-3-propionylimidazolidine 1 -methylallyl-2-(2,4-dichlorophenylimino)imidazolidine I -nonyl-2-(2,4-dichlorophenylimino)imidazolidine.

EXAMPLE 11 This Example illustrates the preparation of pour-on formulations. The following ingredients were mixed to provide a solution in convenient form for application to animals.

1 -Methyl-2-(2,4-dichlorophenylimino)- imidazolidine 5.0% w/v Xylene 20.0% v/v Liquid paraffin 30.0% v/v Maize oil to 100.0% volume Similar pour-on formulations were prepared employing the active ingredients listed in Example 10.

EXAMPLE 12 The activity of compounds against the cattle tick, Boophilus microplus, was tested in the following way.

Two filter papers were each impregnated with 0.4 ml of acetone solution of the test compound. The acetone was allowed to evaporate and one of the filter papers was inserted into the inverted lid of a 5 cm petri dish. A cardboard washer was placed on top of the impregnated filter paper and approximately 50 seven-day old larvae of the Biarra strain of Boophillus microplus were placed within the space enclosed by the washer. The remaining impregnated filter paper was placed on top of the cardboard washer and held in place by inserting the base of the petri dish inside the lid and securing it by means of elastic bands. The whole was placed in a humidified incubator at 260C for 48 hours and then examined. At a concentration of 500 parts per million all of the compounds of formula I named in Examples 1 to 7 gave greater than 50 percent kill, as in addition did the following compounds: 2-(2,3-dichlorophenylimino)imidazolidine 2-(2,4,5-tric hlorophenylimino)imidazolidine 2-(2-methyl-4-chlorophenylimino)imidazolidine 2-(2-chloro-4-methylphenylimino)imidazolidine 2-(2-bromo-4-chlorophenylimino)imidazolidine 2-(4-bromo-2-chlorophenylimino)imidazolidine 2-(2,4-dibromophenylimino)imidazolidine 2-(2-chloro-4-bromophenylimino)imidazolidine 2-(2,4-dimethylphenylimino)imidazolidine 2-(2,4,6-trichlorophenylimino)imidazolidine 1 -methoxymethyl-2-(2,4-dichlorophenylimino)imidazolidine.

EXAMPLE 13 In the following experiments calves were employed that had been given equal inocula of infective larvae of the cattle tick, Boophilus microplus, three times per week for three weeks up to the time of treatment. All parasitic stages, from larvae to gravid females, were thus present at the time of treatment.

The active ingredients were sprayed on the calves to run-off, the spray containing 0.05 per cent active ingredient, which represents a dosage of approximately 4 gm per calf (weighing approximately 130 kilograms). The spray was applied by means of a mechanical hand spray.

An assessment of activity was made by counting the number of gravid female ticks shed by the treated animals and making a comparison with control animals that had not been treated with active ingredient. Both of the following compounds resulted in greater than 70 per cent control l-propionyl-2-(2 4-dichlorophenylimino)imidazolidine l.acetyl-2-(2,4-dichlorophenylimino)imidazolidine.

EXAMPLE 14 The activity of l-propionyl-2-(2,4-dichlorophenylimino)imidazolidine was tested against Sarcoptes scabiei the cause of sarcoptic mange in pigs.

A heavily infested piglet weighing approximately 35 kilograms was sprayed all over with 500 ml of an aqueous dispersion of the active compound at a concentration of 0.1 per cent. The spraywash was applied by means of a mechanical hand spray and particular attention was paid to treating the insides of the ears.

A second spray treatment with 500 ml of the aqueous dispersion was applied eighteen days after the first treatment.

Ear scrapings were taken and examined microscopically at intervals after this treatment and it was found that the mange mite had been completely eliminated.

WHAT WE CLAIM IS: 1. A method for controlling pests harmful to domestic animals which comprises applying to the locus of the pest a compound of the formula:

in which n is 0 to 5, R is halo, alkyl, trihaloalkyl, cyano, alkoxy or alkoxycarbonyl, R' and R2 are each hydrogen, alkyl, alkenyl, alkynyl or acyl and R3 and R4 are each hydrogen or alkyl; or an acid addition salt thereof.

2. A method for controlling ectoparasites which comprises externally applying to livestock a compound as defined in claim 1, in which n is 0 to 3, R is halo or alkyl, R' and R2 are each hydrogen, alkyl, alkenyl or acyl, and R3 and R4 are each hydrogen or alkyl; or an acid addition salt thereof.

3. A method according to claim 2 in which R3 and R4 are hydrogen.

4. A method according to either of claims 2 and 3 in which n is 1 to 3.

5. A method according to any of claims 2 to 4 in which R is halo.

6. A method according to any of claims 2 to 5 in which R' is hydrogen or acyl of the formula R5CO, R2 iS acyl of the formula R'CO, R5 being alkyl of 1 to 10 carbon atoms.

7. A method for controlling ectoparasites which comprises externally applying to livestock a compound of the formula:

in which n is 1 to 3, R is halo, R' is hydrogen or acyl of the formula RSCO and R2 is acyl of the formula R5CO, R5 being alkyl of 1 to 10 carbon atoms.

8. A method for controlling ectoparasites which comprises externally applying to livestock a compound of the formula

in which R' and R2 are each hydrogen, acetyl or propionyl.

9. A method for controlling ectoparasites which comprises externally applying to livestock 1 - propionyl - 2 - (2,4 - dichlorophenylimino)imidazolidine.

**WARNING** end of DESC field may overlap start of CLMS **.

Claims (23)

**WARNING** start of CLMS field may overlap end of DESC **. EXAMPLE 14 The activity of l-propionyl-2-(2,4-dichlorophenylimino)imidazolidine was tested against Sarcoptes scabiei the cause of sarcoptic mange in pigs. A heavily infested piglet weighing approximately 35 kilograms was sprayed all over with 500 ml of an aqueous dispersion of the active compound at a concentration of 0.1 per cent. The spraywash was applied by means of a mechanical hand spray and particular attention was paid to treating the insides of the ears. A second spray treatment with 500 ml of the aqueous dispersion was applied eighteen days after the first treatment. Ear scrapings were taken and examined microscopically at intervals after this treatment and it was found that the mange mite had been completely eliminated. WHAT WE CLAIM IS:

1. A method for controlling pests harmful to domestic animals which comprises applying to the locus of the pest a compound of the formula:

in which n is 0 to 5, R is halo, alkyl, trihaloalkyl, cyano, alkoxy or alkoxycarbonyl, R' and R2 are each hydrogen, alkyl, alkenyl, alkynyl or acyl and R3 and R4 are each hydrogen or alkyl; or an acid addition salt thereof.

2. A method for controlling ectoparasites which comprises externally applying to livestock a compound as defined in claim 1, in which n is 0 to 3, R is halo or alkyl, R' and R2 are each hydrogen, alkyl, alkenyl or acyl, and R3 and R4 are each hydrogen or alkyl; or an acid addition salt thereof.

3. A method according to claim 2 in which R3 and R4 are hydrogen.

4. A method according to either of claims 2 and 3 in which n is 1 to 3.

5. A method according to any of claims 2 to 4 in which R is halo.

6. A method according to any of claims 2 to 5 in which R' is hydrogen or acyl of the formula R5CO, R2 iS acyl of the formula R'CO, R5 being alkyl of 1 to 10 carbon atoms.

7. A method for controlling ectoparasites which comprises externally applying to livestock a compound of the formula:

in which n is 1 to 3, R is halo, R' is hydrogen or acyl of the formula RSCO and R2 is acyl of the formula R5CO, R5 being alkyl of 1 to 10 carbon atoms.

8. A method for controlling ectoparasites which comprises externally applying to livestock a compound of the formula

in which R' and R2 are each hydrogen, acetyl or propionyl.

9. A method for controlling ectoparasites which comprises externally applying to livestock 1 - propionyl - 2 - (2,4 - dichlorophenylimino)imidazolidine.

10. A method according to any of claims 2 to 9 in which the livestock are

cattle or pigs.

11. A method according to claim 10 which comprises treatment of cattle infested with ticks.

12. A method according to any of claims 2 to 11 in which the livestock are treated with an amount of active ingredient within the range of from 0.5 to 75 mg.

per kilogram body weight of the host.

13. A method according to any of claims 2 to 11 in which the livestock are treated witha spray or dip wash containing from 0.005 to 0.5 per cent by weight of active ingredient.

14. A method according to claim 11 in which the cattle are treated with pouror composition at a rate of from 0.5 to 5 gm. active ingredient per beast.

15. A method for controlling an infestation of pests on a cat or dog which comprises applying to the pests a compound as defined in claim 1.

16. A method according to claim 15 which comprises applying a compound as defined in claim 2.

17. A method according to claim 16 which comprises applying 1 - propionyl 2 - (2,4 - dichlorophenylimino)imidazolidine.

18. A cattle or sheep dip comprising 1 - propionyl - 2 - (2,4 - dichlorophenylimino)imidazolidine in association with a surfactant, the nature and proportion of the ingredients being such that, on dilution with an appropriate quantity of water, a stable aqueous composition is produced that is suitable for the treatment of the cattle or sheep.

19. A pesticidal composition in the form of a dispersible powder comprising 1 - propionyl - 2 - (2,4 - dichlorophenylimino)imidazolidine in finely divided form in association with a dispersing agent, the concentration of the active ingredient being from 5 to 95 per cent by weight of the powder.

20. A pesticidal pour-on composition comprising 1 - propionyl - 2 - (2,4 dichlorophenylimino)imidazolidine in the form of a finely divided dispersion of particles having an average diameter of from 0.1 to 20 microns in an aqueous medium, the active ingredient being present to the extent of 2 to 60 per cent by weight.

21. A pesticidal pour-on composition comprising 1 - propionyl - 2 - (2,4 dichlorophenylimino)imidazolidine dissolved in a medium comprising a pharmacologically acceptable oil, the active ingredient being present to the extent of from 2 to 60 per cent by weight.

22. A pesticidal dusting powder suitable for treating a cat or dog comprising 1 - propionyl - 2 - (2,4 - dichlorophenylimino)imidazolidine intimately mixed with a solid pulverulent diluent, the active ingredient being present to the extent of from 1 to 50 per cent by weight of the dusting powder.

23. A pesticidal composition substantially as described with reference to Examples 8 to 11.