HU184221B - Insecticide compositions containing 1-/phenyl-carbamoyl/-imida zoline derivatives as active substances and process for preparing the 1-/phenyl-carbamoyl/-imidazoline derivatives - Google Patents

Abstract

Pesticidal imidazolines are provided of formula wherein X is O or NH; and Y is Br, F, I, -NO2, -OR,-CO2R, -CONR1R2 or -SO2NR1R2, ?, when X is NH, Y may also be chosen from Cl, CN or alkyl of from 1 to 4 carbon atoms, in which R is an alkyl group of from 1 to 18 carbon atoms, and each of R1 and R2, which may be the same or different, is hydrogen or an alkyl group of from 1 to 18 carbon atoms. Pesticidal acid additions salts of the imidazolines are also provided. Methods are described for preparing the pesticides, together with intermediates formed in the preparative methods. Pesticidal formulations containing the pesticides and their use are also described. The pesticides may be used against Arthropods, e.g. against Acarina.

Description

(57) EXTRAS

The present invention relates to an ixodicidal composition comprising a biologically active agent, a solid or liquid carrier, preferably a mineral solid or an aromatic hydrocarbon, and optionally a surfactant, preferably an anionic or nonionic surfactant, such that a biologically active agent is a 1- (phenylcarbamoyl) imidazoline (II) - Formula I

X is oxygen or -NH-,

Y represents a bromine, fluorine or iodine atom, a nitro group or a group -OR or -CO ₂ R and

X represents -NH-,

Y may also represent a chlorine atom or a C 1-4 alkyl group,

R is C 1-4 alkyl in an amount of 0.001 to 35% by weight.

The invention further relates to a process for the preparation of 1- (phenylcarbamoyl) imidazoline derivatives.

Me Me

-1184 221

FIELD OF THE INVENTION The present invention relates to ixodicidal compositions containing 1-phenylcarbamoylimidazoline derivatives and to the preparation of novel 1-phenylcarbamoylimidazoline derivatives.

It has now been found that the imidazoline derivatives of formula I wherein X is oxygen or -NH-;

Y is bromo, fluoroiodo, nitro, or -OR, - CO ₂ R, and

X represents an -NH- group,

Y may also represent a chlorine atom or a C 1-4 alkyl group,

R is alkyl;

they are effective against arthropods, such as their acarina representatives.

Preference is given to compounds of formula Ia which form a narrower group of compounds of formula I wherein X is as defined above and Y ^{1 is} fluorine or bromine, nitro, methoxy or -CO ₂ C ₂ H ₅ , or X- represents NH group and Y ¹ is chlorine.

They may also exist in solvated forms of certain compounds of formula (I).

Preferred compounds of formula (1) are:

1- [N- (4-methoxyphenyl) carbamoyl] -2- (2,3-dimethylphenoxymethyl) -2-imidazoline;

l- [N- (4-chlorophenyl) carbamoyl] -2- (2,3-dimethyl-anilinomethyl) -2-imidazoline;

l- [N- (4-bromophenyl) -carbamoyl] -2- (2,3-dimethylphenoxy) -2-imidazoline;

l- [N- (4-nitrophenyl) -carbamoyl] -2- (2,3-dimethylphenoxy) -2-imidazoline;

- [N- (4-fluorophenyl) carbamoyl] -2- (2,3-dimethylphenoxymethyl) -2-imidazoline; and 1- [N- (4-bromophenyl) carbamoyl] -2- (2,3-dimethylanilinomethyl) -2-imidazoline.

The compounds of formula I are active against arthropods. For example, the formulations containing the compounds of formula I are useful for controlling insects such as Rhipicephalus appendiculatus, Boophilus decoloratus, Boophilus microplus, Rhipicephalus evertsi, Amblyomma hebraeum, Psoroptes ovis and Hyaluma species of animal pests and Tetranychus species.

British Patent No. 1,593,276 discloses 2- (2,3-dimethylphenoxymethyl) -2-imidazoline derivatives and 2- (2,3-dimethylanilinomethyl) -2-imidazoline derivatives. . However, unlike the derivatives of this invention, these known compounds do not contain a phenylcarbamoyl substituent on the imidazole ring. The stability of the known compounds is much lower than that of the 1-phenylcarbamoylimidazoline derivatives of the present invention; Thus, for example, half of the known 2- (2,3-dimethylphenoxymethyl) -2-imidazoline is degraded in aqueous medium at pH 7 within 2 weeks, whereas the 1- [N- (4-chloro- phenylcarbamoyl] -2- (2,3-dimethylanilinomethyl) -2-imidazoline, under the same conditions, undergoes the same degree of degradation in more than 6 months.

The compounds of formula (I) may be prepared by any conventional method for the preparation of compounds of analogous structure.

Thus, the imidazoline derivatives of formula I can be prepared starting from the 2-substituted imidazoline derivatives of formula II, wherein X is a direct addition reaction with an isocyanate of formula III as previously defined for formula I.

The reaction may optionally be carried out in water or in an organic solvent such as chloroform or methylene chloride, preferably a base such as an alkali metal hydroxide, an alkali metal carbonate or an organic tertiary amine base such as triethylamine, pyridine or substituted pyridines or piperidines, e.g. in the presence of pentamethylpiperidine or tetramethylpiperidine. The reaction temperature is generally -70 ° C to 120 ° C, preferably -10 ° C to 40 ° C.

Alternatively, the compounds of formula (I) may be prepared by reacting a compound of formula (IV), wherein X is as defined above, and Q is a halogen, with a suitable active amine of formula (V), wherein Y is as previously described. meaning.

Formulations containing the compounds of Formula I as active ingredients can be used to kill insects, ticks, mites and other arthropods, including free-living arthropods and ectoparasites parasitic on plants, mammals and birds. The compositions of the present invention contain, in addition to the active ingredient, one or more known formulating agents, such as wetting agents, diluents, stabilizers, fillers, emulsifiers, dispersants or surfactants, and other customary excipients.

The formulations may be formulated in aqueous solutions of the compounds of the formula I or aqueous suspensions of the compounds of the formula I, optionally containing suitable surfactants. The composition may be used in the form as it is commercially available or in ready-to-use form, diluted with water. Application to the pests or their immediate surroundings is by spraying or immersion.

Alternatively, a suitable miscible oil may be mixed with a compound of formula (I), optionally in the presence of an equimolar amount of a suitable organic acid, such as oleic acid, to provide salts soluble in organic solvents, and an emulsifier added. The resulting emulsion may be applied by spraying or immersion.

Further formulations are obtained by preparing non-aqueous solutions or suspensions of the compounds of formula (I) in suitable organic solvents. The resulting formulations can be used directly by the pour-on method. The formulations may also be formulated as wettable powders which may be diluted with water and used by immersion or spraying. Other solid compositions, such as powders and granules, may be used directly without dilution.

Further formulations are pastes, fats or gels, which contain the compounds of the formula I together with suitable carriers and which can be applied by spraying to the infected area.

Preferably, the free bases or acid addition salts of formula I are present in an amount of from about 5% to about 35% by weight of the ixodicidal composition (based on the weight of the base). A particularly preferred preparation-21

184,221 wafers contain about 20% of the active ingredient calculated in the same way. The pests and their immediate surroundings are generally treated with formulations containing from 0.001 to 20% by weight of the active ingredient (based on the weight of the base).

The invention is illustrated by the following non-limiting examples.

Example 1

- Preparation of [N- (4-Chloro-phenyl) -carbamoyl] -2- (2,3-dimethyl-anilinomethyl) -2-imidazoline

2- (2,3-Dimethylanilinomethyl) -2-imidazoline (4.20 g, 0.024 mol) was stirred in methylene chloride (90 ml), cooled to 0 ° C, and 3.66 g (0.024 mol) was added dropwise. A solution of 4-chlorophenyl isocyanate in 10 ml of methylene chloride. A white precipitate formed rapidly. Stirring is continued at 0 ° C for 2-3 hours, then the reaction mixture is allowed to warm to room temperature and stirring is continued overnight. The reaction mixture is then concentrated to dryness under reduced pressure and the resulting solid residue is recrystallized from propan-2-ol. 1- [N- (4-chlorophenyl) carbamoyl] -2- (2,3-dimethylanilinomethyl) -2-imidazoline is obtained in the form of white crystals, m.p. 153-155 ° C.

2-6. Examples

In analogy to the procedure of Example 1, the following Examples 2-6 are prepared. can be prepared.

Example 2

- [N- (4-bromophenyl) carbamoyl] -2- (2,3-dimethylphenoxymethyl) -2-imidazoline monohydrate, m.p. 150-151 ° C (white powder).

Example 3 1- [N- (4-Methoxyphenyl) carbamoyl] -2- (2,3-dimethylphenoxymethyl) -2-imidazoline, m.p. 126-127 ° C (white powder).

Example 4

- [N- (4-nitrophenyl) carbamoyl] -2- (2,3-dimethylphenoxymethyl) -2-imidazoline monohydrate, m.p. 182-185 ° C (light yellow powder).

Example 5

- [N- (4-carbethoxyphenyl) carbamoyl] -2- (2,3-dimethylphenoxymethyl) -2-imidazoline, m.p. 153 ° C (white powder).

Example 6 1- [N- (4-Fluorophenyl) carbamoyl] -2- (2,3-dimethylphenoxymethyl) -2-imidazoline, m.p. 172-173 ° C.

Example 7 Preparation of 1- [N- (4-Bromophenyl) carbamoyl] -2- (2,3-dimethylphenoxymethyl) -2-imidazoline

A) 2- (2,3-Dimethylphenoxymethyl) -2-imidazoline (20.4 g, 1.0 mol) was dissolved in methylene chloride (300 mL) and cooled to -65 ° C for 30 min. A solution of 19.8 g (1.0 mol) of 4-bromophenyl isocyanate in 300 ml of methylene chloride is added dropwise. The reaction mixture was allowed to warm to room temperature and allowed to stand for 2 hours. A precipitate forms upon standing of the reaction mixture. The mixture was concentrated under reduced pressure and the residue was recrystallized from acetone. 1- [N- (4-Bromophenyl) carbamoyl] -2- (2,3-dimethylphenoxymethyl) -2-imidazoline monohydrate, m.p. 150-151 ° C.

B) Through the N-chlorocarbonyl derivative of 2- (2,3-dimethylphenoxymethyl) -2-imidazoline

A solution of phosgene (0.5521 g, 0.00549 mol) in toluene (17%) was treated with 15 ml of anhydrous chloroform (3.2 g). The resulting solution was added slowly at 0 ° C with stirring to a solution of 2.40 g (0.115 mol) of 2- (2,3-dimethylphenoxymethyl) -2-imidazoline in 20 ml of anhydrous chloroform. After the addition was complete, the reaction mixture was allowed to stand at room temperature for two hours, then diluted with an equal volume of anhydrous diethyl ether and rapidly quenched. To the filtrate, containing the N-chlorocarbonyl derivative of 2- (2,3-dimethylphenoxymethyl) -2-imidazoline, 1.22 g (0.00714 mol) of freshly distilled 4-bromoaniline were added and the mixture was allowed to stand at room temperature overnight. Thin layer chromatography shows that the major component of the resulting material is the desired product.

The mixture was evaporated to dryness in vacuo and the residue taken up in a mixture of aqueous sodium carbonate solution and dichloromethane. The organic layer was washed with water, dried over magnesium sulfate and evaporated to dryness. The resulting residue was purified as described in Step A to give 1- [N- (4-bromophenyl) carbamoyl] -2- (2,3-dimethylphenoxymethyl) -2-imidazoline identical to that obtained in Step A). .

8-10. Examples

In a manner analogous to that described in Example 1, the following compounds were prepared:

- [N- (4-methylphenyl) carbamoyl] -2- (2,3-dimethylanilinomethyl) -2-imidazoline;

mp 154-155 ° C.

- [N- (4-bromophenyl) carbamoyl] -2- (2,3-dimethylanilinomethyl) -2-imidazoline (m.p. 161.6-162.2 ° C).

Example 11

Blood-filled female ticks of Boophilus microplus strain Biarra are immersed in twenty dilutions of various dilutions of the test compounds. Dilution is carried out immediately prior to the assay by adding an appropriate amount of water to the compositions containing the test compound. The compounds are formulated in a mixed oil as described in Formulation Example 6 or in Formulation 3, Formulation 3

-3184,221, the desired dilution series is prepared by further dilution of the stock solution to a suitable concentration.

After 10 minutes, the ticks are removed from the liquid and then glued on both sides with adhesive tape back to back. They remain in this position for 15 days when determining the number of visible eggs laid. From these data, plotting the percentage inhibition of egg laying as a function of concentration is plotted and the curve determines IR99, the concentration of drug at which egg laying is 99% inhibited.

The results obtained are given in the following Table I.

Table I

Compound Example number IR99 l- [N- (4-chlorophenyl) carbamoyl] -2- (2,3-dimethylaniline-methyl) -2- imidazoline 1 0.029% 1- [N - (4-bromo-m-phenyl) carbamoyl] -2 - (2,3-dimethyl-phenoxymethyl) -2- imidazoline 2 0.0095% 1- [N- (4-methoxyphenyl) carbamoyl] 2- (2,3-dimethylphenoxymethyl) -2-imidazoline 3 0.0038% 1- [N- (4-nitrophenyl) carbainoyl] 2- (2,3-dimethylphenoxymethyl) -2-imidazoline hydrate 4 0.010% 1- [N- (4-Carbethoxyphenyl) carbamoyl] - 2- (2,3-dimethylphenoxymethyl) -2-imidazoline 5 0.019% 1- [N- (4-methylphenyl) carbamoyl] - 2- (2,3-dimethyl-anilino-methyl) -2- imidazoline 8 0.003%

The following formulation examples are intended to illustrate various possible formulations of the ixodicidal compositions of the invention. The active compounds can be applied in such and similar forms to the insects or to the insect threatened area.

The composition of the trademarked compositions used in the examples is as follows:

From the East: Preparation containing xanthan gum.

Dispersol AC: condensation product of formaldehyde and naphthalenesulfonic acid, containing approximately the same amount of the strong β-isomer sodium salt.

Aromasol H: Preparation containing as the main component a mixture of trimethylbenzenes and small amounts of aromatic hydrocarbons having from 9 to 10 carbon atoms.

Formulation Example 1

Dusting agent 1.0 20.0 parts by weight talc 99.0 80.0 parts by weight

100.0 100.0

Formulation Example 2

Wettable powder

agent 25.0 parts sodium dioctyl sulpho succinate 1.0 parts Dispersol AC 2.0 parts kaolin 72.0 100.0 parts 3. Formulation example Aqueous dispersion agent 20.0 parts Keltrol 0.4 parts sodium dioctyl sulpho succinate 0.5 parts water 7.91 100.0 parts 4. Formulation example drench agent 5.0 parts dimethylformamide 85.0 parts Castor oil 10.0 100.0 parts 5. Formulation example Fat agent 6.0 parts vaseline 94.0 parts

100.0

6. Formulation Example

Mixing oil is 10.0 parts by weight of the compound of Example 3

Aromasol H 70.0 parts by weight nonylphenol ethoxylate 20.0 parts by weight

100.0

The active ingredient in each formulation example is 1- [N- (4-chlorophenyl) carbamoyl] -2- (2,3-dimethylphenoxymethyl) -2-imidazoline.

Claims (4)

PATENT CLAIMS An ixodicidal composition comprising a biologically active agent, a solid or liquid carrier, preferably a mineral solid or an aromatic hydrocarbon, and optionally a surfactant, preferably an anionic or nonionic surfactant, characterized in that it is a biologically active agent. A 1- (phenylcarbamoyl) imidazoline derivative of the Formula I in the formula X is oxygen or -NH-, Y represents a bromine, fluorine or iodine atom, a nitro group or a group -OR or -CO ₂ R and X represents a -NH group, Y can also be chlorine or C 1-4 alkyl, R is C 1 -C 4 alkyl in an amount of 0.001 to 35% by weight. 184,221 2. A process for the preparation of 1-phenylcarbamoyl-imidazoline derivatives of the formula (I) X is oxygen or -NH-, Y represents a bromine, fluorine or iodine atom, a nitro group or a group -OR or -CO ₂ R and X represents an -NH group, Y may also be chlorine or C 1-4 alkyl, R is a C1-4 alkyl - preparation, characterized in that ^a) an imidazoline derivative (Π) of formula (III) with an isocyanate of the formula: - wherein Y is as defined above - _one to react with Tatum, or b) reacting a compound of formula (IV) wherein X is as defined in the formula and Q is a halogen atom, preferably chlorine, with an amine of formula (V) in the formula wherein Y is as defined herein. 3. A process according to claim 2 for the preparation of 1- (phenylcarbamoyl) imidazoline derivatives of formula I wherein Y is -OR or -CO ₂ R, R is as defined in the scope of claim 2, X is oxygen, characterized in that the starting material is an isocyanate of the formula (III) in which Y is -OR or CO ₂ R. A process for the preparation of a) (1-phenylcarbamoyl) imidazoline derivatives of formula I according to claim 2 wherein i) Y is methoxy and X is oxygen, or ii) Y is chlorine and X is -NH, or (ii) Y is bromine and X is oxygen, or arc) Y is fluorine and X is oxygen, characterized in that (i) an imidazoline derivative of formula (II) wherein X is oxygen; Reacting an isocyanate of formula (III) wherein Y is methoxy; or (ii) an imidazoline derivative of formula (II) wherein X is -NH, with an isocyanate of formula (III) wherein Y is chloro; or iii) reacting an imidazoline derivative of formula II wherein X is oxygen with an isocyanate of formula III wherein Y is a bromine atom; or iv) imidazoline derivative of formula II wherein X is oxygen; with an isocyanate of formula (III) wherein Y is fluorine. (1 sheet with formulas) Responsible publisher: Zoltán Himer Head of Department ' Published by Technical Publisher 86/2388 Franklin Printing House Gyál - 85-467 5