DE2531606A1 - SUBSTITUTED 2-PHENYLIMINO-THIAZOLINE, METHOD OF MANUFACTURING AND USE AS EECTOPARASITICIDE - Google Patents

Description

Bayer Aktiengesellschaft

Central Division ^D Patents. Trademarks and licenses

509 Leverkusen. Bayerwerk

Er-Iz Ia (Pha)

Substituted 2-phenylimino-thiazolines, Process for their production and their use as ectoparasiticides

The present invention relates to new substituted 2-phenylimino-thiazolines _f a process for their preparation and their use as ectoparasiticides.

It has already become known that 2-phenylimino-thiazoline compounds can be used as active ingredients in pesticides (see German Auslegeschrift 1 218 210 and Switzerland. Patent 439,858).

However, the compounds of the aforementioned intellectual property right publications are against animal ectoparasites and especially zekken ineffective.

The compound from Switzerland which is structurally closest to the present active ingredients according to the invention. Patent 439,858 is in the application text with active ingredients according to the invention in In terms of their tickicidal effectiveness.

It has been found that the new substituted 2-phenyliminothiazolines of the general formula I.

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in which
R ¹ and R ²

(D

may be the same or different and represent optionally substituted alkyl represents optionally substituted alkyl or ■ halogen,

represents alkyl, cycloalkyl or alkenyl and represents an integer from O to 2,

strong ectoparasiticidal effect, especially against acarids exhibit.

It has also been found that the substituted 2-phenylimino-thiazolines can be used of the formula (I) obtained when substituted phenylthioureas of the formula II

«4

NH-C-NH-R

(II)

in which
R / R, R, R

and η have the meaning given above,

with halogenoacetaldehyde or halogenoacetaldehyde-releasing compounds.

Surprisingly, show the novel substituted 2-Phenylimino-thiazoline in contrast to the structurally closely related thiazoline compounds from Swiss patent specification 439 858 a highly pronounced ectoparasiticide Effect.

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The compounds according to the invention are thus an enrichment of technology.

If you use N- (2,4-dimethyl-pheny1) -N'-methyl-thiourea and chloroacetaldehyde as starting materials, the course of the reaction can be represented by the following equation:

H- S

³ Il

-NH-C-NH-CH ₃ "+ Cl-CH ₂ -CHO '(III)

CH

J ^

^Β3 Π

-> CH _- <'7-N = C. J> + HCl (IV)

3 \ / ^ NT

I ^{+ H} 2 °

CH ₃

The resulting hydrochloric acid is bound by bases (e.g. with NaOH).

In the formula I stands as optionally substituted alkyl R ^, R and R straight-chain or branched alkyl with preferably 1 to 6, especially 1 to 4 carbon atoms. Examples are optionally substituted methyl, ethyl, n.- and i.-Propyl, n, -, i.- and t-butyl, called.

The alkyl R is straight-chain or branched alkyl with preferably 1 to 6, especially 1 to 4 carbon atoms. Examples are optionally substituted methyl, ethyl, n.- and i.-Propyl, called n.-, i.- and t.-Butyl.

4th
Alkenyl R is straight-chain or branched alkenyl with preferably 2 to 6, in particular 2 to 4, carbon atoms. Examples include vinyl, allyl, crotyl, methallyl, β, β-dimethylvinyl and butene- (3) -yl- (1).

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The halogen R in the general formula (I) is preferably fluorine, chlorine, bromine and iodine, in particular chlorine and bromine.

4th
The cycloalkyl R is mono-, bi- and tricyclic cycloalkyl with preferably 3 to 10, in particular 3, 5 or 6 carbon atoms. Examples are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclo [2.2 Λ J heptyl, bicyclo C 2.2.2. J cc tyl and called adamantyl.

12 3

The alkyl radicals R, R and R of the formula (I) can be one or carry several, preferably 1 to 3, in particular 1 or 2, identical or different substituents. As substituents are listed as an example:

Alkoxy with preferably 1 to 4, in particular 1 or 2 carbon atoms, such as methoxy, ethoxy, n.- and i.-propyloxy and n.-, i.- and t.-butyloxy; Alkyl-thio with preferably 1 to 4, especially 1 or 2 carbon atoms, such as methylthio, ethylthio, n.- and i.-Propylthio and n.-, i.- and t.-Butylthio.

The substituted phenylthioureas used as starting compounds of the general formula (II) are known and can be prepared in a simple manner by known methods, either by reacting substituted phenyl isothiocyanates of the general formula (V) with aliphatic amines of the general formula (VI):

(V)

+ H ₂ NO

(VI)

(II)

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or by reacting substituted phenylamines from nilc my formula (VIT) with alkyl ο-5 alkenyl! isothiocyanater de general formula (VIII):

Y ⁿ

SCN-R-

** _ R ¹ - ^ 7-NH-C-NH-R

(VII) (VIII) ill)

12 3 4 where the radicals R, R, R, R and η in the more general Formulas (V), (VI) / (VII) and (VIII) have the meanings given above own.

The halogenaceous aldehydes or halogenacetaldehyde-releasing compounds used according to the invention are already known,

Examples of the substituted phenylthioureas of the formula CI) used as starting materials according to the invention are :

N- ( 2,4-Dimethyl-phenyl) -N'-methyl-thiourea

"-ethyl-

" ^M -propyl-"

"" -isopropyl- "

¹¹ -al IyI-

"-methallyl-" "" -crotyl- "

¹¹ "-cyclopropyl-"

"" -butyl-

¹¹ -tert-butyl- "

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N- (2-methyl-4-ethyl-phenyl) -N'-methyl-thiourea

"-ethyl-

"" -allyl- "

N- (2-Äthy1-4-me thy1-pheny1) -N'-me thy1-

"-ethyl-N- (2,4-diethyl-phenyl) -N'-methyl-thiourea

-N'-ethyl-

N- (2,4,5-trimethyl-phenyl) -N'-methyl-thiourea

¹¹ -ethyl- ¹¹ -allyl-

"" -cyclopropyl- "

N- (2,3,4-trimethyl-phenyl) -N • -methy1-thiourea

"-ethyl-" -methallyl-

N- (2,4,6-triinethy 1-phenyl) -N'-methy 1-thiourea N- (3-Methy 1-2,4-diet 1-phenyl) -N'-methyl-thiourea f N- (5-Methy1-2,4-diethy1-phenyl) -N'-methy1-thiourea f N- (5-chloro-2,4-dimethyl-phenyl) -N'-methyl-thiourea N- (2,3,4,5-tetramethyl-phenyl-N'-methyl-thiourea

As examples of those used as starting products according to the invention Halogen acetaldehydes or halogen acetaldehyde-releasing compounds may be mentioned:

Chloroacetaldehyde, bromoacetaldehyde, chloroacetaldehyde dimethylacetal, Bromoacetaldehyde diethyl acetal, methyl (1,2-dichloroethyl) ether, Ethyl (1,2-dichloroethyl) ether, 2-chloromethyl-1,3-dioxolane.

As examples of the starting compounds of the formula (VII) used in the preparation of the compounds of the formula (II) are mentioned:

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2,4-Dimethylaniline 2-Methy1-4-ethyl-aniline 2-Methy1-4-propylaniline 2-Methy1-4-butyl-aniline 2-Methy1-4-isopropy1-aniline 2-Methy1-4-isobutyl-aniline 2- Methy1-4-sec-butyl-aniline 2-Methy1-4-tert-butyl-aniline 2-ethyl-4-methyl-aniline 2, 4-diethylaniline 2-ethyl-4-isopropylaniline 2-ethyl-4- tert .-buty1-aniline 2,4-diisopropyl-aniline 2,4-di-sec-butyl-aniline 2,4-di-tert-butyl-aniline 2,4,5-trimethyl-aniline 2,3,4 -Trimethy1-aniline 2,4,6-trimethy1-aniline 3-Methy1-2,4-diethyl-aniline 5-methyl-2,4-diethylaniline 5-chloro-2 _f 4-dimethylaniline 5-bromo-2,4- dimethyl aniline 5-fluoro-2,4-dimethyl aniline 2,5-dimethyl-4-chloro-aniline 2,3,4,5-tetramethyl-aniline 2-ethyl-3,4-dimethyl-aniline 2-methyl -4-methoxymethyl-aniline, 4-methyl-2-methoxymethyl-aniline, 4-methyl-2-methylthiomethyl-aniline

As examples of alkyl or alkenyl amines of the general Formula (VI) are mentioned:

Methylamine
Ethylamine
Propylamine
Isopropylamine
Butylamine
sec-butylamine isobutylamine
tert-butylamine AlIylamine
Methylamine
Crotylamine
Cyclopropylamine

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The isothiocyanates of the formulas (V) or (VIII) can be prepared from the arylamines of the formula (VII) or alkylamines of the formula (VI) by known methods, for example by reacting arylamines of the formula * (VII) with thiophosgene or by reacting N-aryl or N-alkyl-dithiocarboxylic acid salts with phosgene or oxidizing agents according to the information in Houben-Weyl 'Methods of Organic Chemistry ¹ , Volume IX, pages 867 to 878. The implementation of the isothiocyanates of the formulas (V) or (VIII) with the amines of the formulas (VII) or (VI) to the thioureas of the formula (II) can be carried out by heating in inert solvents or in the melt with or without the addition of basic catalysts such as triethylamine (see Houben- Weyl 'Methods of Organic Chemistry', Volume IX, pages 889 to 891).

The substituted phenylthioureas are according to the invention of the general formula II with haloacetaldehyde or haloacetaldehyde-releasing Compounds to the active ingredients of general formula I implemented.

The reaction of the substituted phenylthioureas of the formula II with haloacetaldehyde or haloacetaldehyde-releasing Connections are preferably carried out in a solvent with the addition of an acid-binding agent.

The following solvents can be used, for example: alcohols such as methanol, ethanol, butanol, ketones such as acetone, butanone, methyl isopropyl ketone, ethers such as 1,2-diinethoxyethane, diisopropyl ether, tetrahydrofuran, dioxane, carboxylic acid derivatives such as acetonitrile, ethyl acetate, dimethylformamide, Aromatics such as benzene, toluene, xylene, chlorobenzene; Aliphatics and cycloaliphatics, such as gasolines and Ligroine with boiling ranges between 60 ° to 180 ⁰ C, cyclohexane; Chloraliphatics such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane.

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253160C • ι ■

The following acid-binding agents can be used, for example: inorganic bases such as sodium hydrogen carbonate / sodium / carbonate, potassium carbonate, trinatrium phosphate, sodium hydroxide , potassium hydroxide or organic bases such as triethylamine or benzyldimethylamine,

For the implementation of substituted phenylt; ^. Ureas of the '..- rmein with haloacetaldehydes or haloacetaldehyde abfoaltei the compounds become equimolar or approximately equimolar Amounts of the two components used, in particular ■■ i be expedient to use a small excess (1 to 15 mol%).:; ..; Halogenacetaldehyde or halogenacetaldehyde-releasing compound to use. For this purpose, the substituted phenylthioh- ~ n ~ substance of the formula (II) dissolved or suspended in a solvent and the halogenoacetaldehyde or the halogenoacetaldehyde-releasing compound is slowly added. The acid-binding Means can also be provided or only after use be admitted. The reaction is carried out at temperatures from 0 C to the boiling point of the solvent used, for example 150 C, carried out; the preferred temperature range is from 20 ° C to 80 ° C.

The batches are expediently worked up by mixing with water to remove the salts, and extracting the reaction product with a water-immiscible solvent and crystallization or distillation. If the melting point of the reaction product is high enough, the aqueous suspension can can be worked up directly by filtration and drying.

If the condensation reaction is carried out without the addition of an acid-binding agent, the 2-arylimino-3-alkylthiazolines can can also be isolated in the form of their salts, for example the hydrochlorides. On the other hand, they can be in shape of the bases isolated 2-arylimino-3-alky! -thiazolines also after-

Le A] 6

• 4P.

be converted into their salts by reaction with inorganic or organic acids, for example into the Hydrochlorides, hydrobromides, sulfates, phosphates, formates, oxalates, succinates, trifluoroacetates, benzenesulfonates, naphthalene-1,5-disulfates.

As examples of the 2-arylamino-3-alkyl-thiazolines which can be prepared according to the invention of the general formula (I) the following may be mentioned:

2- (2,4-Dimethyl-phenylimino) -3-methyl-thiazoline 2- (2,4,5-Trimethy1-phenylimino) -3-methyl-thiazoline 2- (2,4-Diaethyl-phenylimino) -3- methyl-thiazoline 2- (2,4-dimethyl-phenylimino) -3-ethyl-thiazoline 2- (2,4-dimethyl-phenylimino) -3-propy1-thiazoline 2- (2,4-dimethyl-phenylimino) -3 -isopropy1-thiazoline 2- (2,4-dimethyl-phenylimino) -3-butyl-thiazoline 2- (2,4-dimethyl-phenylimino) -3-isobutyl-thiazoline 2- (2,4-dimethyl-phenylimino) - 3-tert-butyl-thiazoline 2- (2,4-dimethyl-phenylimino) -3-allyl-thiazoline 2- (2,4-dimethyl-phenylimino) -3-methally1-thiazoline 2- (2,4-dimethyl- phenylimino) -3-crotyl-thiazoline 2- (2,4-dimethyl-phenylimino) -3- (β-dimethyl-vinyl) -thiazoline 2- (2-ethy1-4-methyl-phenylimino) -3-methyl-thiazoline 2- (2-methyl-4-ethyl-phenylimino) -3-methyl-thiazoline 2- (2,4-dimethyl-1-5-chlorophenylimino) -3-methyl-thiazoline 2- (2,3,4-trimethyl) -phenylimino) -3-methyl-thiazoline 2- (2,3,4,5-tetramethyl-phenylimino) -3-methyl-thiazoline 2- (2,4,6-trimethyl-phenylimino) -3-methyl-thiazoline 2 - (2-methyl-4-isopropyl-phenyl imini) -3-methyl-thiazoline 2- (2-tert. Buty1-4-methyl-phenylimino) -3-methyl-thiazoline 2- (2,4-di-isopropy1-phenylimino) -3-methyl-thiazoline 2- (2,4-diaethyl-phenylimino) -3-ally1-thiazoline 2- (4-Methy1-2-methoxymethyl-phenylimino) -3-methyl-thiazoline 2- (4-Methy1-2-methylthiomethyl-phenylimino) -3-methyl-thiazoline.

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6 0 9 8 8 5/1 I 2 4-

The new active ingredients of the general formula (I) and their salts have a strong acaricidal action, especially against Acarids which, as animal ectoparasites, attack domesticated animals such as cattle, sheep and rabbits. Simultaneously the 2-arylimino-3-aikylthiazolines have only a low toxicity to warm-blooded animals. They are therefore well suited for combating animal ectoparasites from the class of the acarids. In addition, however, they also have an effect against insects.

Examples include: mange mites, lice and dipteras and their larvae.

As economically important ectoparasites that play a major role especially in tropical and subtropical countries, the Australian and South American beef ticks Boophilus microplus, the South African beef ticks, may be mentioned Boophilus decoloratus, both of the Ixodidae family.

Over time, ticks in particular are used as a control agent Phosphoric acid esters and carbamates used up to now have become resistant, so that the control success in is increasingly being called into question in many areas. To the Securing economic livestock farming in the infested areas there is an urgent need for means with which all stages of development, i.e. larvae, nymphs, metanymphs and adults, including resistant strains, such as the genus Boophilus can be controlled safely. For example, they are highly resistant to the phosphoric acid esters used to date in Australia, the Mackay strain, the Biarra strain and the Mt Alford strain of Boophilus microplus.

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The active ingredients according to the invention are against the normally sensitive as well as against the resistant strains, for example of Boophilus, equally effective. In the usual application on the host animal, they act both directly on all forms that parasitize the animal and strongly ovicidal on the adult forms, so that the tick reproductive cycle is both in the parasitic phase on the animal as well as in the non-parasitic phase. The oviposition is prevented, the development and inhibits hatching. Particularly noteworthy is the rapidly occurring exciting effect on all parasitic ones Forms that give up their sucking posture, wander around in an unphysiological way on the host animal, fall off and finally die (detaching effect) as well as especially the good effect against the metanymph stages, which experience has shown to be difficult to fight.

Furthermore, they act in the same way on all stages of development multi-host ticks such as Amblyomma spp. Hyalomma spp, Rhipicephalus spp., Ixodes spp., Hemaphysalis spp., Dermacentor spp.

A detaching effect can also be seen in insects, for example in lice such as Hematopinus spp. and with Diptera like Melophagus ovinus.

Depending on the intended form of application, the new active ingredients be converted into the formulations customary in practice, such as solutions, emulsions, suspensions, powders, Pastes and granulates. These are produced in a known manner, e.g. by mixing the active ingredients with extenders, i.e. liquid solvents and / or carriers, optionally with the use of surface-active agents, i.e. Emulsifying and / or dispersing agents, e.g. in the case of Using water as an extender, organic solvents can optionally be used as auxiliary solvents.

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ORDINAL INSPECTED

809885/1124

Possible solvents are, for example: aromatics (e.g. xylene, Benzene, orthodichlorobenzene, trichlorobenzene) paraffins (e.g. Petroleum fractions), alcohols (e.g. methanol, ethanol, isopropanol, butanol), strongly polar solvents such as dimethylformamide, N-methyl-pyrrolidone, Dimethyl sulfoxide and also water.

The following solid carriers may be mentioned: natural rock soles (e.g. kaolins, clays, talc, chalk) synthetic inorganic carriers (e.g. highly dispersed silicic acid, silicates); as emulsifiers: non-ionic as well as anionic or cationic emulsifiers such as polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, e.g. alkyl aryl polyglycol ethers; Alkyl sulfonates and aryl sulfonates, quaternary ammonium salts with longer alkyl groups. Use as a dispersant called: lignin, sulphite waste liquors and methyl cellulose.

The formulations generally contain between 0.1 and 95% by weight of active ingredient, preferably between 0.5 and 90% by weight. The use concentrations are produced from the formulations (see above) by diluting them with water. Depending on the application, they can be varied over a wide range and are between 10 and 50,000 ppm (g / g), preferably between 50 and 500 ppm »

The application is carried out in the usual way, e.g. by spraying, pouring on, atomizing or by bath (dip).

The formulations or the ready-to-use solutions nor other aids or active ingredients, such as disinfectants or specially suitable insecticides.

The aqueous solutions or emulsions of the active ingredients according to the invention have good stability under practical conditions, so that the ready-to-use application forms even for longer periods Stand and remain effective in a pH range of 7-9 for three months and longer.

Tick test

Solvent: 35 parts by weight of ethylene glycol monomethyl ether, 35 parts by weight of nonylphenol polycola ether

Mix to prepare a suitable formulation three parts by weight of active ingredient with seven parts of the above-mentioned solvent-emulsifier mixture and diluted the resultant Emulsion concentrate with water to the desired concentration.

Adult, fully sucked in these active ingredient preparations Female ticks of the species Boophilus microplus (sensitive or resistant) immersed for a minute. After diving, 10 female specimens of the different tick species were transferred one this in PetrJsrhalen, whose bottom with a corresponding large filter disc is occupied.

The effectiveness of the active ingredient preparation is determined after 10 days by determining the inhibition of oviposition compared to untreated control ticks. The effect is expressed as a percentage off, where 100% means / that no more eggs were laid and 0% means that the ticks laid eggs in normal quantities.

Tested active ingredient, tested concentration, tested parasites and the results obtained are shown in the following table.

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Active ingredient effect on Boophilus concentr. microplus (Biarrain ppm. Trunk) in%

link

2- (3-methyl-phenyl) -imino-3,4-dimethyl- thiazolidine known from Switzerland. Pat. 439

10,000

1,000

100

0
0
0

compound according to the invention

10,000

3,000

.000

300

100

30th

10

0.3

100 100 100 100 100 100 100? 50 * -50 0

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example

In vivo tick test on Boophilus miqroplus

3 parts of active ingredient are 7 parts of a mixture of equal parts by weight of ethylene glycol monomethyl ether and Mixed nonylphenyl polyglycol ether. The emulsion concentrate obtained in this way is adjusted to the desired in each case with water Application concentration diluted.

Cattle are sprayed with the active ingredient preparation obtained in this way, those with resistant tick larvae of the species Boophilus microplus, Biarra strain, have been infected several times (infection 12 times at an interval of 2 days).

The effect of the active ingredient preparation is determined by determination the number of adult female ticks that develop on the treated cattle. That number will compared to the number of adult female ticks that develop on untreated cattle. A connection is more effective, the fewer female ticks develop after treatment.

The number of adult females in the treated and untreated females is used as a measure of the severity of the infestation prior to treatment Animals develop in the last three days prior to the time of treatment.

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Effectiveness of the compound of the formula according to the invention CH.

, ■ ö-y

CH.

in the pour-on method at different concentrations geo '^ übe Boophilus microplus (Biarra strain). All stages of development:; n ir vivo (cattle)

Acting substance concentration in mgAg

10 cntr.

Days before

Treat -2 - +0

342 2004

Number of ticks with fertile clutches

Days after treatment

+ 1-3

0 2414

0 2377

7-9

0
1716

1-12 13-15

0 126

C 363

15-18] '19-21 y £ h

0 133

101

Multe

I I

Nymphs

Metanymphs

Metal larvae

d vx

Approximate stage of development at the time of treatment

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Effectiveness of the compound of the formula according to the invention

in hand spray at various concentrations against Boophilus microplus (Biarra strain). (All stages of development in vivo (cattle),

Effective
material-
focus
tr ation
in ppm Number of ticks with fertile clutches Days
before
Hand 1.
-2 - +0 Days after treatment + 1-3 4-6 7-9 10-12 13-15 16-18 19-21 £ + 1- + 21 Effect in 500
250
125
Contr. 1361
1140
414
2004 0
0
2
2414 0
0
0
2377 0
0
0
1716 0
0
0
126 0
0
0
363 0
0
0
133 0
0
0
101 0
0
0
7230 100
100
99.96

MuI te

Nymphs

Larvae

Metanymphs

Metal larvae

Approximate stage of development at the time of treatment

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Effect of the compound according to the invention according to Example 3 in hand spray against Boophilus microplus (Biarra strain). All stages of development in vivo (cattle).

Effective
material-
Concentrate
tration
in ppm Number of ticks with fertile clutches Days
before
Hand 1.
-2 - +0 Days after treatment + 1-3 4-6 7-9 10-12 13-15 16-18 19-21 £ + 1-4-21 Effect in 250
Contr. 1079
1856 5
1461 0
862 O
100? O
ί 478 O
92 O
42 0
29 5
3972 99.9

Adult Nyn ^ hen Larvae

1 I 1

Metanyirphs

Metal larvae

Approximate stage of development at the time of treatment

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Effect of the compound according to the invention according to Example 4 in the hand spray on Boophilus microplus (Biarra strain). All stages of development in vivo (cattle).

Effective
material-
focus
tration
in ppm Number of ticks with fertile clutches Days
before
Hand 1.
-2 - + Ο Days na <: h treatment + 1-3 4-6 7-9 10-12 13-15 16-18 19-21 £ + 1 - * - 21 Effect in 1000
Contr. 40
1401 0
1040 0
829 0
1106 O
477 O
405 O
204 O
50 0
4111 100

Adult nymph larvae

} ) 1 * ■ ■ I

Metanymphs

Metal larvae

t I

Approximate stage of development at the time of treatment

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Effect of the compound according to the invention according to Example 5 in hand spray against Boophilus microplus (Biarra Stamu) All stages of development in vivo (cattle).

Effective
material-
Concentrate
tration
in ppm Number of ticks with fertile clutches Days
before
Hand 1.
-2 - + Ο Days after treatment + 1-3 4-6 7-9 10-12 13-15 16-18 19-21 157
4111 . ..... ......., .....
Effect in 94 250
Contr. 1070
1401 43
1040 9
829 13th
1106 63
477 22nd
405 7th
204 0
50

Adult nymph larvae ι I 1> - -

Metanyrrphs of metal larvae

> ι * ~~ -

Approximate »stage of development at the time of treatment

■ · A, 16 5.35.

- 18th

Example 1 : ° "*

2- (2,4-Dimethyl-phenyl) -iitiino-3-methyl-thiazoline

10og N- (2,4-Dimethyl-phenyl) -N'-methyl-thiourea are suspended in 400 ml of acetone and at 10 ⁰ C to 15 ° C for 90 a 45% aqueous solution of g Chloracet-aldehyde was added dropwise. The batch is then refluxed for 2 hours and most of the acetone is then distilled off. The residue is stirred with 1.5 l of water and 50 ml of 45% strength sodium hydroxide solution, the oily reaction product is taken up in methylene chloride, dried over potassium carbonate and fractionated: boiling point 145-15O ° C./0.5 torr, yield 96 g; 86% of the total The compound crystallizes when inoculated or left standing for a long time.

The N- (2,4-dimethyl-phenyl) -N'-methyl-thiourea used as the starting compound can be made in the following ways:

200 g of 4-amino-1,3-dimethylbenzene are in 200 ml of dioxane and Dissolved 100 ml of triaethylamine and added 124 g of methyl isothiocyanate. When the exothermic reaction is over and the detection of the amine turns out to be negative due to the diazotization reaction, it is diluted with 1 liter of warm water and 500 ml of acetic acid, and suctioned the reaction product and washed with water and methanol. Yield 282 g; 90% of the theory; F: 150-152 ° C.

Example 2 :
2- (2,4-Dimethyl-phenyl) -imino-3-methyl-thiazoline

150 g of N- (2,4-dimethyl-phenyl) -N'-methyl-thiourea become Dissolved in 800 ml of acetone and added 200 g of finely powdered potassium carbonate and 60 ml of water. Then one drips

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10 - 15 ° C 117 g of methyl (1,2-dichloro-äthyD ether (94% strength) are added The mixture is then stirred for a further 1 hour at 50 ⁰ C., then filtered to remove the salts and the acetone filtrate by 4. 1 water is stirred with 100 ml of 45% strength sodium hydroxide solution. The separated oil is taken up in methylene chloride, the methylene chloride phase is washed several times with water, dried over potassium carbonate and the methylene chloride is distilled off. 150 g of oily reaction product are obtained which, with 500 ml of petroleum ether at - The mixture is stirred at 10 ° C. and crystallized by inoculation, followed by filtering, washing with pre-cooled petroleum ether (boiling point 40-60 ° C.) and drying in vacuo According to gas chromatographic analysis, the compound produced in this way is 98.5% pure.

NMR and IR spectra as well as elemental analysis are available with the adopted constitution in line.

Example 3 :

2- (2,4,5-trimethyl-phenyl) -imino-3-methyl-thiazoline

30 g of N- (2,4,5-trimethyl-phenyl) -N ¹ -methy! -Thiourea are dissolved in 250 ml of acetone and 40 g of potassium carbonate and 20 ml of water are added. Then, at 10 ⁰ C, 22 g of methyl (1,2-dichloräthyD ether (92% strength) are added dropwise. The mixture is stirred for 2 hours at 50 ° and then poured into 2 1 of water and 50 ml of 45% sodium hydroxide solution. The precipitated oily The reaction product is taken up with methylene chloride, the extract is washed several times with water, dried over potassium carbonate and fractionated: K: 163-168 ° C / 0.7 Torr, yield 27 g; 81% of theory.

The compound crystallizes on standing.

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The thiourea used as the starting material can be as follows getting produced:

180 g of 5-amino-1,2,4-trimethylbenzene are dissolved in 200 ml of methylene chloride dissolved and at 15-20 C to a mixture of 208 g of thiophosgene, 600 ml of methylene chloride, 500 ml of water and 180 g Calcium carbonate was added dropwise. The mixture is then heated under reflux until the evolution of carbon dioxide has ended. After that, will filtered, the methylene chloride phase separated off, dried over potassium carbonate and fractionated: boiling point: 132-136 ° C / 5, O Torr, Yield 203 g of 2,4,5-trimethylphenyl isothiocyanate.

100 g of 2, 4,5-trimethyl-phenyl isothiocyanate are added at 10 ⁰ C in a solution of 47 g of methylamine in 400 ml of methanol. The mixture is stirred for 12 hours at 20 ° and heated under reflux for a further 1 hour. The batch is then diluted with 1 liter of water, and the reaction product is filtered off, washed and dried. Yield 130 g of N- (2,4,5-trimethyl-phenyl) -N'-methyl-thiourea (85% of theory), temperature: 181-182 ° C.

Alternatively, the same connection can also be made using the following procedure getting produced:

150 g of 5-amino-1,2,4-trimethyl-benzene are dissolved in 100 ml of dioxane and 150 ml of triethylamine and a further 84 g of methyl mustard oil are added. The reaction is exothermic and the mixture is allowed to come to reflux. As soon as the amine can no longer be detected by the diazotization reaction, the batch is diluted with 1 liter of white spirit (boiling point: 60-80 ° C.), cooled to 20 ° C. and the reaction product is filtered off with suction. Yield 217 g of N- (2,4,5-trimethyl-phenyl) -N'-methylthiourea (94% of theory..), F: 179-181 ⁰ C.

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Example 4

2- (2,4-Diaethyl-pheny! Imino) -3-methyl-thiazoline)

30 g of N- (2,4-diaethyl-phenyI) -N ¹ -methyl-thiourea are stirred in 250 ml of acetone and 27 g of chloroacetaldehyde (45% strength aqueous solution) are added dropwise. The mixture is then refluxed for 2 hours and the acetone is then distilled off. The residue is stirred with 250 ml of methylene chloride and 60 ml of 20% strength sodium hydroxide solution, the methylene chloride layer is separated off, washed twice with 200 ml of water, dried over potassium carbonate and fractionated.

Bp: 149-153 ° C / 0.14 torr; Yield 25.0 g; 75% d. Th. The distillate freezes when standing.

The thiourea used as the starting material can be made from

2 1 4-ΙΉä-t-hyVniiin can be prepared with methyl isothiocyanate as in

Example 3 given; F: 132-134 ° C.

Example 5 :

2- (2,4-dimethylphenylimino) -3-ethyl-thiazoline

30.0 g of N- (2,4-dimethyl-phenyl) -N'-ethyl-thiourea become
Stirred with 250 ml of acetone and slowly added 27.0 g of chloroacetaldehyde (45% aqueous solution). The mixture is then refluxed for 2 hours and most of the acetone is then distilled off. The residue is with 250 ml of methylene chloride and
60 ml of 20% strength sodium hydroxide solution are stirred, the methylene chloride layer is separated off, washed with water, dried over potassium carbonate and fractionated. Bp: 147-152 ° C / 0.38 torr; Yield 25.0 g> 75% of theory

■ A 16 533 - 22 -

The following thiazoline derivatives can be prepared analogously:

2- (2,4-dimethyl-phenylimino) -3-propyl-thiazoline

Bp: 155-162 ⁰ _{CZO 7} S torr; 2- (2,4-dimethyl-phenylimino) -3-allyl-thiazoline

Bp: 153-156 ° C / 0.6 torr; 2- (2-methyl-4-ethyl-phenylimino) -3-methyl-thiazoline

Bp: 146-15O ° C / 0.14 torr; 2- (2,4, 5-trimethy1-phenylimino) -3-ethyl-thiazoline

Bp: 165-173 ° C / O.9 torr.

The N-aryl-N'-alkylthioureas required as starting materials can be prepared according to the methods described in Examples 1 and 3; these are the following connections :

N- (2,4-Dimethy1-pheny1) -N'-ethy! -Thiourea F: 77-79 ° C;

N- (2,4-Dimethyl-phenyl) -N'-propyl-thiourea

F: 66-68 ° C;

N- (2,4-Diraethy1-pheny1) -N'-ally1-thiourea

F: 58-60 ° C, -

N- (2-Methy1-4-ethy1-pheny1) -N "-methy1-thiourea

F: 127-128 ° C;

N- (2,4,5-trimethyl-phenyl) -N'-ethyl-thiourite

F: 133-135 ° C.

Γ, ο λ 16 533 -

s 8; ΐ

The following thiazoline derivatives can be prepared analogously to Example 5 will:

2- (2-ethyl-4-methyl-phenyl-imino) -3-methyl-thiazoline Bp 149-152 ° C /1.0 torr

2- (2-methyl-4-tert-butyl-phenylimino) -3-methyl-thiazoline Kp 169-173 ⁰ C /1.1 torr

2- (2,5-dimethyl-4-chloro-phenylimino) -3-methyl-thiazoline Kp 168-170 ⁰ C /1.0 torr; stiffens

2- (2,4-Dimethyl-5-chloro-phenylimino) -3-methyl-thiazoline Bp 176-18O ° C / 1.7 Torr

The following additional N-aryl-N'alkylthioureas required as starting materials can be produced according to example 1 and 3:

N- (2-ethyl-4-methyl-phenyl) -N'-methyl-thiourea F: 126-128 ° C

N- (2-methyl-4-tert-butyl-phenyl) -N'-methyl-thiourea F: 166-167 ° C

N- (2,5-dimethyl-4-chloro-phenyl) -N'-methyl-thiourea Q:

N- (2 ^ -Dimethyl-S-chloro-phenyl) -N'-methyl-thiourea F: 173-174 ° C

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Claims (7)

Patent claims : ι '1) / Substituted 2-phenylimino-thiazolines of the formula I. , ~ 3, (D in which
R ¹ and R ² and may be the same or different and represent optionally substituted alkyl represents optionally substituted alkyl or halogen,
represents alkyl, cycloalkyl or alkenyl represents an integer from 0 to 2 and their salts. 2) Substituted 2-phenylimino-thiazolines of the formula Ia, III (Ia) in which
R ¹ and R ¹¹ III IV IV can be the same or different and for Are alkyl with 1 to 4 carbon atoms, for alkyl with 1 to 4 carbon atoms or Chlorine stands, for alkyl with 1 to 4 carbon atoms or for alkenyl with 2 to 4 carbon atoms stands, Le A 16 533 - 24 - 609885/1124 and η stands for an integer from 0 to 2, and their salts. 3) Process for the preparation of compounds of formula I. (R ³ ), R ² - (D in which R ¹ and R ² E ⁴ and may be identical or different and represent optionally substituted alkyl represents optionally substituted alkyl or halogen
represents alkyl, cycloalkyl or alkenyl represents an integer from 0 to 2. characterized in that compounds of the formula n S - ^ Vnh-onh-r ⁴ nh-onh-r ⁴ (II) R ¹ in which RfR, R 4th
R and η have the meaning given above. with haloacetaldehyde the haloacetaldehyde-releasing Reacts compounds and the end products, if necessary, converted into their salts with acids. Le A 16 533 - 25 - S0S885 / 1 124 3 ©. 4) Process for the preparation of compounds of the formula (Ia) R and R can be the same or different and for R for alkyl with 1 to 4 carbon atoms or R for alkyl with 1 to 4 carbon atoms or for in which Are alkyl with 1 to 4 carbon atoms, for alkyl mi Chlorine stands, for alkyl mi '■ Alkenyl having 2 to 4 carbon atoms, and η stands for an integer from 0 to 2, and their salts,
characterized in that compounds of the formula (R ¹¹¹ I _n S vV-NH-C-NH-R ^IV (Ha) in which R ¹ , R ¹¹ , R ¹¹¹ , IV
R and η have the meaning given above, are reacted with chloroacetaldehyde or compounds which split off chloroacetaldehyde and the end products are optionally converted into their salts with acids. 5) Medicines, characterized by a content of at least one substituted 2-phenyl-imino-thiazoline according to claim Le A 16 533 - 26 - 609885/1 124 6) Process for the preparation of ectoparasiticidal agents, characterized in that substituted 2-phenyliminothiazolines according to claim 1 mixed with inert, non-toxic, pharmaceutically suitable carriers. 7) Method for combating and destroying ectoparasites on the animal clothing of warm-blooded animals that have been infected by them, thereby characterized in that substituted 2-phenyliminothiazolines according to Claim 1 are allowed to act. Le A 16 533 - 27 - INSPECTED 609885/1 1 24