CA1108620A

CA1108620A - Imidazolines

Info

Publication number: CA1108620A
Application number: CA293,379A
Authority: CA
Inventors: Frederick C. Copp; Alexander D. Frenkel; Peter T. Roberts; David Collard
Original assignee: Wellcome Foundation Ltd
Current assignee: Sanofi Aventis France
Priority date: 1976-12-20
Filing date: 1977-12-19
Publication date: 1981-09-08
Also published as: JPS5395968A; NL7714063A; AU521328B2; MC1173A1; ES465208A1; AR225271A1; IL53640A0; LU78718A1; SE444563B; FR2374308A1; FR2374308B1; DK565277A; AU3174777A; ES473432A1; SE7714407L; IE46119L; IL53640A; IT1093073B; CH642821A5; DE2756639A1

Abstract

ABSTRACT

Compounds of formula (I):

(I):

wherein Ar is an unsubstituted or mono-, di or tri-substituted phenyl radical in which the substituents are the same or different and are selected from alkyl, alkoxy, halogen, hydroxy, cyano, amino, trifluoromethyl or nitro and in which any two adjacent carbon atoms on the phenyl ring may optionally be joined by a carbon chain having 3 or 4 carbon atoms;
X1 is O or NH;
R1 and R2 are the same or different and are hydrogen or alkyl; and Z is a group SOnR8 or a group in which X2 is O, S or NR4;
R3 is alkyl, aryl, alkyloxy, aryloxy or NR5R6;
R4 is alkyl, aryl, alkyloxy, aryloxy, alkylthio, arylthio or NR5R6;
R5 and R6 are the same or different and are hydrogen, alkyl, aryl, COR7 or SO2R7;

R7 is alkyl, aryl, alkoxy or aryloxy;
n is 1 or 2;
R8 is alkyl, aryl or NR9R10; and R9 and R10 are the same or different and are hydrogen, alkyl or aryl, provided that when Ar is unsubstituted phenyl, X1 is NH, R1 and R2 are H, Z is

Description

~1~`86ZO

This invention relates to imidazolines, their pre-paration and intermediates therefor, pesticidal formulations containing the imidazolines, and to their use as pesticide~.
We have discovered that the compounds of formula (I) below and their acid addition salts have activity against Arthropods, in particular against members of the Order Acarina.
Compounds of formula (I) are:-Ar-Xl-C ~/ ~ (I) R

wherein Ar is an unsubstituted or mono-, di- or tri-sub-stituted phenyl radical in which the substituents are the same or different and are selected from alkyl, alkoxy, halo-: gen, hydroxy, cyano, amino, trifluoromethyl or nitro and in which any two adjacent carbon atoms on the phenyl ring may optionally be joined by a carbon chain having 3 or 4 carbon atoms;
X is O or ~H:
Rl and R2 are the same or different and are hydrogen or alkyl; and SO 8 ~X
g P nR or a group -C \ in which X is 0, S or NR ;
R i s alkyl, aryl, alkyloxy, aryloxy or NR5R ;
R4 i S alkyl, aryl, alkyloxy, aryloxy, alkylthio, arylthio or ~R R ;
R5 and R are the same or different and are hydrogen, alkyl, aryl, CoR7 or So2R7;

- 2_ ., - : . ~.

r J~¢~ .2~
R is alkyl, aryl, alkyloxy or aryloxy;
n is 1 or 2;
R8 is alkyl, aryl or NR9R10; and R and Rl are the same or different and are hydrogen, alkyl or aryl, provided that when Ar is2unsubstituted phenyl, and R2 are H, Xl is NH, Z is C \ 3 and x2 is 0, R is not - methyl.
In formula (I), halogen includes chloro, bromo, and fluoro and the alkyl and alkoxy groups and moieties each have 1 to 4 carbon atoms. Certain compounds of formula (I) may exist in their solvated forms. The group Ar in formula (I) is preferably unsubstituted or has substituents selected from alkyl (preferably methyl) and/or halogen (preferably chloro) groups.
The term "aryl" as used herein includes phenyl or naphthyl either unsubstituted or substituted with one or re substituents, the substituent(s) being the same or different and preferably selected from alkyl, alkoxy, halo~en, nitro, cyano and amino.
Preferred compounds of formula (I) include those wherein:-(i) Ar is phenyl or 2,3-dimethylphenyl; and/or (ii) Z is -C ~ 3 wherein x2 is O or S and R3 is NR5R .

- Particularly preferred compounds of formula (I) are:-l-N-phenylcarbamoyl-2-(2,3-dimethylphenoxymethyl)-

2-imidazoline:

-- 3 _ `` ' 11~D~6Z~

l-~-(~-Naphthyl)carbamoyl-2-(2,3-dimethyl-phenoxymethyl)-2-imidazoline;
l-N-(4-chlorophenyl)carbamoyl-2-(2,3-dimethyl-phenoxymethyl)-2-imidazoline; and 1-~-(4-cyanophenyl)carbamoyl-2-(2,3-dimethyl-phenoxymethyl)-2-imidazoline.
The compounds of formula (I) and their acid addition salts have activity against Arthropods, in parti-cular against the Order Acarina. The compounds of formula (I) may be used to control pests such as Rhipicephalus appendiculatus, Boo~ilus decoloratus, Boophilus microplus, Rhipicephalus evertsi, Amblyomma hebraeum, PsoroPtes ovis and HYaloma species on animals and Tetranychus species on plants.
The compounds o~ formula (I) may be prepared by any known method for the preparation of compounds of an analogous structure.
In particular the compounds of formula (I) may be prepared from 2-substituted imidazolines of formula (II) or an acid addition salt thereof, Rl Ar_Xl_ R H

wherein Ar, Xl, Rl and R2 are as defined above, either by a direct addition reaction with an iqocyanate or isothio-; cyanate (to give a compound of formula (I) where Z is an M-substituted carbamoyl or thiocarbamoyl group): a ketene ;;

- 4 _ :, 2~
(to give a compound of formula (I) where Z is an acyl group) or a carbodiimide (to give a compound of formula (I) where Z is an amidino group); or by a substitution reaction with a compound of formula (III):
Z-X' (III) where Z is as defined above and x' is a leaving group such as halo (e.g. in acid chlorides or halo-formate esters), acyloxy (e.g. in acid anhydrides), alkoxy or alkylthio (e.g. carbamates, imidates, thiocarbamates or thioimidates) or sulphonyloxy (e.g. in mixed anhydrides).
In one particular application of the above sub-stitution reaction compounds of formula (I) wherein Z is a thiocarbamoyl group may be prepared by the reaction of a compound of formula (II) with a compound of formula (III) wherein Z is a thiocarbamoyl group and X' is NH2 (i.e.
z-X' is a thiourea).
The reaction may be effected optionally in water or an organic solvent, such as chloroform or methylene chloride, preferably in the presence of a base such as an alkali metal hydroxide, and alkali metal carbonate, or a tertiary organic base, such a~ triethylamine, pyridine or substituted pyridines or piperidines, e.g. pentamethyl-piperidine or tetramethylpiperidine; and generally at temperatures of -70C to 120C, preferably at temperatures of -10C to 40C.
Compounds of formula (I), in particular those wherein Z is not a strong electron withdrawing group, may be prepared by reacting an ethylenediamine of formula (IV) or salt thereof, ., ~ - 5 _ - : : - ,: . .
: . : : : .
. .. .. ~ ', ~ ,., .-: : . :.: :. .

1~862~
2 H2CH2NH z (IV) wherein Z is as defined hereinabove, with an appropriate phenoxyalkyl or anilinoalkyl carboxylic acid or a reactive derivative thereof such as imidate, thioimidate, imido-halide, ester, amidine, thioamide, nitrile or carboxyalkyl-thioamide. These reactants may be conveniently represented by formula (V):

Rl Ar-Xl-l_Q (V ) wherein Ar, Xl, Rl and R2 are as defined hereinabove and Q

is a carboxyl group or a reactive derivative thereof which produces the imidazoline ring structure of formula (I) when reacted with a compound of formula (IV):

Suitable derivatives include:-D OIAlk -C (imidate), -C-OAlk (orthoester), Oalk OAlk D NH NH

-C (thioimidate), -C (imido halide), SAlk Hal O ~ NH

-C \ (ester), -C (amidine), Oalk NH2 ~; - 6 _ - ~ . . . :. ~ .
: :: : ::: .. .: :; - .: : :
- .~: . . :-. :. -: ~ . . ,- .. . -: - :
~.- :, :, . .: .. . -~ s -C (thioamide), -C-N (nitrile), and -C (carboxyalkylthioamide) ~ HC02Alk:
wherein 'Alk' is an alkyl group having 1 to 6 carbon atoms.
The conditions under which this reaction may be carried out of course depends upon the nature of the start-ing materials used, and a liquid medium may be present or absent; high and low temperatures may be used, and various pressures employed.
When the carboxylic acid derivative is an imidate, this is preferably in the form of an acid addition salt such as a hydrogen halide salt, and may be prepared from the nitrile and a suitable anhydrous alkanol such as ethanol or methanol in the presence of dry diethyl ether or chloroform and hydrogen chloride at a low temperature.
The reaction may be carried out at a temperature in the range of -20C to ambient temperature. The reaction with an ethylenediamine of formula (IV) is conducted in an inert anhydrous medium such as chloroform, methylene chloride or ether. The reactants are preferably heated under reflux until reaction is complete.
The thioimidate intermediates in the form of acid addition salts may be prepared from the corresponding nitrile by reaction with an alkyl mercaptan and a hydrogen halide 7 _ - .:
. ~ . , .
', ~ ' ' ' ';, -,:, ~. ~
. ~ , -- , 62~

gas at low temperatures about ~C, in the presence of dry diethyl ether. The thioimidate may then be reacted with an ethylenediamine of formula (IV) the reaction being effected at the reflux temperature of the reaction mixture.
The ester intermediates may be conveniently pre-pared from the corresponding acid by known methods, and the acid itself may be prepared from the corresponding nitrile. They may then be reacted with an ethylenediamine of formula (IV), preferably in the presence of a liquid medium which may be polar or non-polar. The reaction is preferably carried out at an elevated temperature.
The compounds of formula (I) may be prepared from the imidohalide intermediates by reaction with an ethylene-diamine of formula (IV), under anhydrous conditions in the presence or absence of an acid acceptor and optionally at ', an elevated temperature. The reaction mixture may include a polar or non-polar liquid medium such as a lower alkanol or an ether.
The amidine intermediate in the form of the base or acid addition salts thereof, is preferably converted to a compound of formula (I) by heating under reflux with an ethylenediamine of ,formula (IV) in the presence of a polar or non-polar liquid medium, for example a lower alkanol, until ammonia ceases to be evolved. The amidine intermediates themselves may be prepared by any known method, but conveniently from the corresponding imidates by reaction with ammonia.

,; ' ;;; i, ~: - , : ' ' . :

, ~

6Z~
The thioamide and amide intermediates may be prepared from .-the corresponding nitriles or by any other convenient method and may be converted into compounds of formula (I) by heat-ing with an ethylenediamine of formula (IV), at a reflux or higher temperature, in the presence or absence of a polar or non-polar solvent. Con~eniently the reactions are partly effected under reduced pressure to induce the removal of ammonia and/or hydrogen sulphide from the reaction mixture.
10The nitrile intermediates are reacted in the pre-~; sence or absence of a liquid medium with an ethylenediamine of formula (IV) or a salt thereof; the reaction may be carried out in the presence of hydrogen sulphide. A
liquid medium such as a lower alkanol may be included in the reaction mixture which may be heated to reflux temperature, or to a higher temperature in a closed vessel, optionally in the presence of an inert gas such as nitrogen.
It will of course be understood that where the intermediate is the carboxylic acid, the ester or thioamide, there may be isolated as an intermediate the acylethylene-diamines of formula (VI):

Rl Ar-X -C - C ~ (VIj R2N-cH2cH2NH2 Z

wherein Ar, Xl, Rl, R2 and Z are as defined above and W is oxygen or sulphur and these compounds may themselves be ~.: : : ~

2~
converted in situ to a compound of formula (I), either by separate treatment with a dehydrating agent such as calcium oxide or by continuing the reaction to completion under the original conditions giving rise to a compound of formula (I).
The compounds of formula (I~ may be prepared by the reaction of a phenol or amine of formula (VII), or an O- or ~-metal compound thereof;
Ar-X -H (VII) wherein Ar and X are as defined in formula (I) with a compound of the formula (VIII):

N

11~ N ~ (VIII) wherein R , R and Z are as defined in formula (I), and V
is a leaving group derived from a suitable inorganic or organic acid. Suitable derivatives are halo, such as chloro, iodo, or bromo, alkylsulphonyloxy or arylsulphonyloxy such as ~-toluene-sulphonyloxy.
The compounds of formula (VIII) may be in the form of their bases or acid addition salts thereof. The reaction 20 is carried out in an inert liquid medium which is prefer-ably a polar liquid such as acetonitrile or isopropanol, or may be dimethylsulphoxide, sulpholane, methyl ethyl ketone, dimethylformamide, acetone, dimethylacetamide, ~-methyl-2-pyrrolidone, or mixtures of the foregoing. In the ca~e where V is chloro in a compound of formula (VIII), then a small cataly~ic quantity of an iodide salt for example, - 10 _ ~1~8~2~

sodium iodide, or a phase transfer catalyst such as a quaternary ammonium salt such as benzyltrimethylammonium chloride may advantageously be included in the reaction mixture. The reactants may be heated together under an inert atmosphere such as nitrogen at the reflux temperature of the reaction mixture. x2 The compounds of formula (I) wherein Z is -C

and R3 is alkoxy, aryloxy or NR R may also be prepared by reacting a compound of formula (IX):

Ar-Xl-C

R
~yC\

X Y

in which Ar, Xl, X2, Rl and R2 are as defined above and Y is a leaving group (such as halo, acyloxy, alkoxy, alkylthio, S , SH, sulphonyloxy or carbalkoxy) with a suitable active hydrogen-containing compound of formula (X):

Rll H (X) wherein R is alkoxy, aryloxy or ~R5R and R5 and R6 are a~ -defined above.
In one particular aspect this method may be applied to the preparation of compounds of formula (I) in which Z is a carbamoyl group by treatment of compound (IX) in which Y is -SR" and x2 is ~R4 where R is as defined above and R"
is an alkyl group with a suitable active-hydrogen containing ~,.~., .

1~8~
compound of formula (X) above. The intermediate compounds of formula (rX) in which ~ is SR" and X is ~R may be pre-pared from compounds of general formula (XI):

Ar-Xl_ ¦2 ~ (~I) R ¦
,~ C\

wherein Ar, Xl, Rl, R2 and R" are as defined above. x2 The compounds of form~la (I), wherein Z is C
~ R

R3 is as defined above and x2 is NR4 where R is as defined in formula (I) above, may also be prepared by reacting a compound of formula (II) above with an imidoyl dihalide of formula (XII):

R -N=c(Hal)2 (XII) where R4 i9 as defined in formula (I) above and Hal is chloro, bromo or iodo, to give an intermediate of formula ; (IX) above wherein x2 is R4-N and Y is Hal which may then be converted to a compound of formula (I) by the above described method.
The compounds of formula (I) may be isolated from the reaction mixture as the free base or in the form of an acid addition salt. The bases may be converted into acid addition salts thereof by known techniques with the aid of the appropriate acid, and salts of the compound may also be converted into the free bases or into other acid addition ~ ., '`

i2~
salts.
For use as a pesticide, the compounds of formula (I) may be presented in the form of their free bases, or as acid addition salts thereof. Suitable salts of formula (I) include hydrohalide, sulphate, nitrate, phosphate, thio-cyanate, acetate, propionate, stearate, naphthenate, per-chlorate, benzoate, methanesulphonate, ethanesulphonate, tosylate and benzenesulphonate acid addition salts thereof.
The compounds of formula (I) may be used as to combat insects, ticks, mites and other arthropods including free living arthropods and those which are ectoparasites of plants, mammals and birds and may be used alone or in com-bination with an additive which may take the form of one or more of the carriers used in the formulation art, such as: wetting, diluting, stabilising, thickening, emulsifying, dispersing or surface active agents or other standard carrier ingredients.
A formulation may be an aqueous solution of an acid addition salt of a compound of formula (I), or a sus-pension of a compound of formula (I) in water, and may beused alone or in combination with suitable surface active agents. $he formulation per se may be used alone or diluted in water for application to the pests or their immediate environment by way of spraying or dipping.
A formulation may be in the form of a miscible oil comprising a compound of formula (I) in the form of its free base or with equimolar quantity of a suitable organic acid, such as oleic acid or naphthenic acid, to provide a salt soluble in organic solvents, and emulsifiers, and are applied as an emulsion by way of spraying or dipping.

, ~ ~ .

62~

A formulation may be a non-aqueous solution or suspension of a compound of formula (I) in a suitable organic solvent for the direct application by the "pour-on"
; method. A formulation may also take the form of a wettable powder for dilution with water and application by dipping and spraying. Other solid foxmulations may also be used for direct application without dilution, such as dusts, powders and granules.
A further formulation may be a paste, grease or gel containing a compound of formula (I) and a suitable carrier, and may be applied by spreading the formulation over the infected area.
An acid addition salt or base of a compound of formula (I) is preferably present in a pesticidal formulation in an amount between 5 and 80Yo, calculated by weight of the base, and particular~y preferred formulations containing about 20%, calculated by weight of the base. The concent-ration of a compound of formula (I) applied to the pests or their immediate environment may be in the range of 0.001%-20 20%~ calculated by weight of the base.
It will be appreciated from the foregoing thatwhat we will claim may comprise any novel feature described herein, principally and not exclusively, for example:-(a) A novel substituted phenoxyalkyl or anilinoalkyl imidazoline compound of formula (I) and acid addition salts thereof;
(b) A method of preparation of a novel compound of formula (I) and acid addition salts thereof;
(c) A method of controlling arthropod pests, parti-cularly members of the Order Acarina, by applying to the ~: ;: : :: - . :: ; :
.. .. . - .

8~Z~) pest or the pest's environment a compound of formula (I);
(d) A pesticidal formulation comPriSing a compound of formula (I) and a carrier thereof; and (e) A method of making a formulation comprising an admixture of a carrier and a compound of formula (I).
The following Examples are provided by way of an illustration of the present invention and should not be construed as in anyway constituting a limitation thereof.

, .
Preparation of 2-(2,3-dimethYlphenoxymethyl)-l-acetYl-2-im~dazoline A solution of acetic anhydride (3.0 ml; 0.032 moles) in diethyl ether (10 ml) was added dropwise, during 10 minutes, to a stirred suspension of 2-(2,3-dimethylphenoxy-methyl)-2-imidazoline (6.12 g; 0.030 mole) (prepared from 0-ethyl-2,3-dimethylphenoxyacetimidate and ethylene diamine) in - diethyl ether (100 ml) cooling the mixture to keep its temperature below 20C. After stirring for 2 hours the reaction mixture was filtered and the precipitate recrystal-lised from acetone to yield white crystals of 2-(2,3-dimethyl-phenoxymethyl)-l-acetyl-2-imidazoline, m.p. 127-130C.
Analysis: Calculated C 68.27, H 7.37, N 11.37%, Found:
C 68.13, H 7.44, N 11.13%.

2-(2,3-Dimethylphenoxymethyl)-l-N,N-dimethYlthiocarbamoyl-2-imidazoline A solution of dimethylthiocarbamoyl chloride (2.47 g; 0.020 mole) in chloroform (10 ml) was added dropwise dur-ing 10 minutes, to a stirred solution of 2-(2,3-dimethyl-phenoxymethyl)-2-imidazoline (4.08 g; 0.020 mole) prepared -~ ~ -' . : . ,.

.

. :
.
, -- ,' .` .,:,:

8~Z~

as in Example 1 - and triethylamine (2.0 g; 0.20 mole) in chloroform (50 ml) cooling to keep the reaction below 5C.
The reaction temperature was then allowed to rise to room temperature and finally the reaction was refl-~xed for 5 hours. After cooling the reaction mixture was washed with water, dried and~evaporated. The residue was recrystal-lised from isopropanol to yield white crystals of 2-(2,3-dimethylphenoxymethyl)-l-(~,~-dimethylthiocarbamoyl)-2-imidazoline, m.p. 124-127C. Analysis: Calculated C 61.84, H 7.27, ~ 14.42%. Found: C 62.15, H 7.64, ~ 14.35%.

_ 2-(2,3-Dimethylphenoxymethyll-l-(~methYlthiocarbamoYl)-2-imidazoline A solution of methyl isothiocyanate (1.46 g, 0.20 mole) in chloroform (10 ml) was added dropwise during 10 minutes, to a stirred solution of 2-(2,3-dimethylphenoxy-methyl)-2-imidazoline (4.08 g, 0.020 moles) prepared as in Example 1 - in chloroform (50 ml) cooling to keep the reaction below 5C. The reaction mixture was then allowed to warm to room temperature and finally refluxed for 5 hours.
Chloroform was then evaporated ln vacuo and the residue recrystallised from isopropanol to yield white crystals of 2-(2,3-dimethylphenoxymethyl)-1-N-methylthio carbamoyl-2-imidazoline, m.p. ca 100C with decomposition.
lH -NM~ (deuterochloroform - tetramethylsilane internal standard):-.~ =. , .
';, ., , :
- - - ~:: . : .
-: :

. . ~: .
. . ..

z~

8.1-8.3 ~ lH Broad singlet 6.8-7.2 6 3H Multiplet 5.0 ~ 2H Singlet NMR spectra consistent with the proposed

3.6-4.5 ~ 4H Multiplet structure 3.1 ~ 3H Doublet 2.2 ~ 6H Doublet l-N=Phenylcarbamoyl-2-(2,3-dimethylanilinomethyl)-2-imidazoline 2-(2,3-Dimethylanilinomethyl)-2-imidazoline (4.20 g 0.02~ moles) was stirred in methylene chloride (90 ml) cooled to 0C and a solution of phenyl isocyanate (2.84 g;
0.024 moles) in methylene chloride (10 ml) was then added dropwise. A white precipitate formed rapidly. Stirring was continued for 2-3 hours after the addition at 0C, the reaction mixture then allowed to reach ambient temperature and stirring was continued overnight. The reaction mixture was then evaporated to dryness under reduced pressure and the solid residue so obtained recrystallised from propan-2-ol to yield white cry~tals of 1-N-phenylcarbamoyl-2-(2,3-dimethylanillnomethyl)-2-imidazoline (0.735H20) m.p. 137C.

l-N-~2,3-DimethYlphenoxycarbonyl)-2-(2,3-dimethylPhenoxY-. methYl)-2-imidazoline 2-(2,3-Dimethylphenoxymethyl)-2-imidazoline 3.0 g; 0.0147 moles) was dissolved in dry chloroform (~40 ml) and cooled to 0c. Tetramethylpiperidine (2.07 g, 0.0147 moles) in dry chloroform (~7 ml) was then added to the cooled, stirred solution. 2,3-~imethylphenylchloroformate (2.71 g; 0.0147 moles as a 30% w/v solution in benzene) ' 21~
:

was slowly added. A white precipitate formed and stirring was continued at 0C for 2 hours after which time the ¦ reaction mixture was allowed to rise to ambient temperature.
Tetramethylpiperidine hydrochloride was precipitated by the addition of dry acetone and removed by filtration. The filtrate was evaporated to dryness under reduced pressure and the white residue recrystallised from propan-2-ol to give 1-N-(2,3-dimethylphenoxycarbonyl)-2-(2,3-dimethylphenoxy-¦ methyl)-2-imidazoline, m.p. 126-127C.

1 10 EXAMPLES 6 to 27 !
¦ By methods analogous to those described in Examples 1 to 5 above the compounds of Examples 6 to 27 below are also prepared.

1~ l-N-Methyloxycarbonyl-2-(2,3-dimethylphenoxy-methyl)-2-imidazoline, m.p. 120C.

,, l-N-Methylcarbamoyl-2-(2,3-dimethylphenoxy-methyl)-2-imidazoline, m.p. 147-150C. (dec.).

l-N-Phenylthiocarbamoyl-2-(2,3-dimethylphenoxy-methyl)-2-imidazoline, m.p. 102-104C.
¦ EXAMPLE 9 l-N-4-Toluenesulphonylcarbamoyl-2-~2,3-dimethyl-phenoxymethyl)-2-imidazoline, m.p. 120C.

l-N- (a -Naphthyl)carbamoyl-2-(2,3-dimethyl-phenoxymethyl)-2-imidazoline, m.p. 156-158C.

K

, ' , , .. ' ,' ,', ' ' : ,, ; ,. : ., z~

.
l-N-(4-Chlorophenyl)carbamoyl-2-(2,3-dimethyl-phenoxymethyl)-2-imidazoline, m.p. 132C.

l-N-(4-Cyanophenyl)carbamoyl-2-(2,3-dimethyl-phenoxymethyl)-2-imidazoline, m.p. 172-174C.

l-N-Phenylcarbamoyl-2-phenoxymethyl-2-imidazoline, m.p. 170C.

l-N,N-Diphenylcarbamoyl-2-(2,3-dimethylphenoxy-methyl)-2-imidazoline, m.p. 143-145C.

l-N-~-Tolycarbamoyl-2-(2,3-dimethylphenoxy-methyl)-2-imidazoline, m.p. 137C.

l-N-Phenylcarbamoyl-2-(a-phenyloxyethyl)-2-imidazoline, m.p. 159C.

1-N-(~-Naphthyl)carbamoyl-2-phenoxymethyl-2-imidazoline, m.p. 160-163C.

l-N-Cyclohexylcarbamoyl-2-(2,3-dimethylphenoxy-methyl)-2-imidazoline, m.p. 63C.

l-N-Phenylcarbamoyl-2-(2-chloroanilinomethyl)-2-imidazoline, m.p. 169~C.

l-(N-Phenyl-N-methyl)carbamoyl-2-(2,3-dimethyl-phenoxymethyl)-2-imidazoline, m.p. 112C.

. : ~

2~
EX~NPLE 21 l-~-Phenylcarbamoyl-2-(~,~-dimethylphenoxy-methyl)-2-imidazoline, m.p. 81-85C.

l-N-Hexadecylcarbamoyl-2-(2,3-dimethylphenoxy-methyl)-2-imidazoline, m.p. 76-77C.

l-~-(~-Naphthyl)carbamoyl-2-(3-methylanilino-methyl)-2-imidazoline, m.p. 146C.

l-~-Phenylcarbamoyl-2-(2-chloroanilinomethyl)-2-imidazoline, m.p. 168-169C.

1-~-(2,6-Dimethylphenyl)carbamoyl-2-(2,3-dimethyl-phenoxymethyl)-2-imidazoline perchlorate salt, m.p. 221-l-N-(2,3-Dichlorophenyl)carbamoyl-2-(2,3-dimethyl-phenoxymethyl)-2-imidazoline, m.p. 175-180C.

l-N-Phenylcarbamoyl-2-(3-methoxyphenoxymethyl)-2-imidazoline, m.p. 101C.

Preparation of l-methanesulPhonYl-2-(2,3-dimethYlphenoxY
methYl)-2-imidazoline 2-(2,3-Dimethylphenoxymethyl)-2-imidazoline (8.0 g: 0.0392 moles) was dissolved in dry ether (75 ml) and sufficient dry chloroform (50 ml) and the solution cooled in ice (sufficient chloroform was used to prevent pre-cipitation of the imidazoline on cooling). Methanesulphonyl - ~ . .. .
'::: .: :

: ~

chloride (4.50 g, 0.0393 moles) was added dropwise to the cold, stirred solution. When the addition was complete pentamethylpiperidine (6.08 g; 0.0392 moles) was added and the reaction mixture heated under reflux until tlc showed that reaction was complete (~3 hrs). The reaction mixture was then concentrated under reduced pressure and the residue extracted with a water/chloroform mixture (1:1:
~00 ml). The chloroform layer was washed with water, dried over magnesium sulphate and evaporated under reduced pres-sure to give a residue which was recrystallised from iso-propanol to give l-methanesulphonyl-2-(2,3-dimethylphenoxy-methyl)-2-imidazoline, m.p. 142-143C.

By a method analogous to that used in Example 28, l-benzenesulphonyl-2-(2,3-dimethylphenoxymethyl)-2-imidazoline, m.p. 108-110C, was prepared.

Preparation of l-N-phenYlcarbamoyl-2-(2,3-dimethylphenoxy-methYl)-2-imidazoline (A) A solution of 2-(2,3-dimethylphenoxYmethyl)-2-imidazoline (20.4 g, 1.0 moles) in methylene chloride (300 ml) was cooled to -65C and a solution of phenyliso-cyanate (11.9 g; 1.0 moles) in methylene chloride (300 ml) added dropwise during 30 minutes. The reaction mixture was then allowed to warm to ambient temperature and left to stand for 2 hours, when a precipitate had formed. The reaction mixture was evaporated under reduced pressure and the residue recrystallised from acetone to give l-~-phenyl-carbamoyl-2-(2,3-dimethylphenoxymethyl)-2-imidazoline, m.p. 150-152C.

. .
.

(B) via the N-Chlorocarbamoyl adduct of 2-(2,3-dimeth~l-pheno~methyl)-2-imidazoline A l~h solution of phosgene in toluene ~3.2 g con-taining 0.5521 g., 0.00549 moles COC12) in dry chloroform (15 ml) was added slowly with stirring at 0C to a solution of 2-(2,3-dimethylphenoxymethyl)-2-imidazoline (2.40 g, 0.0115 moles) in dry chloroform (20 ml). When addition was complete the reaction mixture was left at ambient temperature for 2 hours, diluted with an equal volume of dry diethylether and rapidly filtered. The filtrate, which contained the ~-chlorocarbamoyl adduct of 2_~2,3-dimethylphenoxymethyl)-2-imidazoline, was treated with freshly distilled dry aniline (0.664 g. 0.00714 moles) and the mixture left at ambient temperature overnight at which time tlc showed that the major compound was the desired product. The mixture was evaporated to dryness in vacuo and the residue taken up in a mixture of aqueous sodium carbonate and dichloromethane The organic layer was washed with water, dried over magnesium sulphate and evaporated to dryness to give a residue which was purified as described in (A) above to give l-~-phenyl-carbamoyl-2-(2,3-dimethylphenoxymethyl)-2-imidazoline, identical with that obtained in (A) above.

.
; Engorged female ticks of the Biarra Strain of Bbophilus microPlus are immersed, in groups of 20 ticks, per concentration in a range of dilutions of the compound under test. The wash is prepared immediately prior to the test by dilution (with water) of the compound under test.
The constituents may be in the form of miscible oil or wettable powder formulations. The desired range of con-," - -:

8~ii2~) centrations for the test is obtained by further dilution of the master solution or wash.
The ticks are removed from the wash after 10 minutes, dried, and stuck dorsal down on double-sided adhesive tape. They remain in this position for 14 days when the numbers laying viable eggs are determined. From this data a regression line is plotted (concentration against % inhibition of egg-production) and the IR90 and IR99 (concentrations at which 9~/O and 99% inhibition respectively of egg-production occurs) determined.
The results obtained are shown in Table 1 below.

; ~
Compound Example No. IR90 IR99 l-~-Phenylcarbamoyl-2-(2,3-dimethylphenoxy-methyl)-2-imidazoline 30 ~ 0.016%

l-~-(~-~aphthyl)-carbamoyl-2-(2,3-di-methylphenoxymethyl)-2-imidazoline 10 0.0032% 0.0054%

l-N-Phenylcarbamoyl-2-phenoxymethyl-2-imidazoline 13 ~ 0.2%

Test compounds were formulated in polyethylene-glycol and injected into ticks at a site just ventral to the mouth parts. After 14 days the percentage inhibition of egg production (IR) was determined. The results are shown in Table 2 below.

, -:

1362~

H O ~i o O ,~ o o ~ 0 u~ ~ I` t` ~ ~ ~ a~

~ O ,_~
, 'i '~ ~
~' ~ ~
~ æ ~ I NO ~
c ~ c ' ~ ~ e ~
e E.~ eb-~ 1 e ,c ,~
o I O~ O :~ R ~ `
I O I NN N-- N O I ~ I~`i N I
nl b ~-- 0 _ -- ta ~ I
U~
O i~--I b ~ ,C --/ ~ I b ---rl O
I ~1 1 1 ~ 1 ~ ~ ~ ~1 ,1 1 ,I E
~`I O t~ a Io ~ 1 o ~d I N I I ~~ ~~j ~ ~ 1~ e o ~ , N ,4 ~ ~ e, ,1 ~ ~
~ U ~ R ~ ~ X ~1, X~ 'a (d I - ~I N ,1 ~ O ~ U I ~ N
" e ~ e E~ b e ~ E ~ I
$1 $~ $~ $~ ~ $~ $~ $~ $~ $~

i~ _ 24 _ , .; ~ -.. ~ :

::

2~) The following formulations are given to illustrate the way in which the pesticidal compounds of the invention can be applied to pests or environments susceptible to pest attack.

Dustinq Powders Active Compound 1.0 20.0 parts by wt.
Talc 99.0 80.0 " "
100. 0 100. 0 10FORMULATIO~ 2 Wettable Powder Active Compound 25.0 parts by wt.
Sodium Dioctyl Sulphosuccinate 1.0 `' "
Dispersol ACA 2.0 " "
Kaolin 72.0 " "
100.O
FORMULATIO~ 3 Aqueous Dispersion Active Compound 20.0 parts by wt.
Keltrol 0.4 " "
SodiumDioctyl Sulphosuccinate 0.5 Water 79.1 " "
100. 0 _ 25 -, Pour-On Active Compound 5.0 parts by wt.
Dimethyl Formamide85.0 Castor Oil 10.0 "
100. 0 Grease Active Compound 6.0 parts by wt.
1~ Petroleum Jelly94,0 "
100 ~ O r , FORMULATION 6 Miscible Oil s, Compound from Example 22 10.0 parts by wt.
Aromasol H 70.0 " "
Nonyl Phenol Ethoxylate 20.0 " "
100.0 , ~ - 26 -- , . : - .

- : . ,. ~ ,

Claims

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A compound of formula (I):

(I) wherein Ar is an unsubstituted or mono-, di or tri-sub-stituted phenyl radical in which the substituents are the same or different and are selected from alkyl, alkoxy, halogen, hydroxy, cyano, amino, trifluoromethyl or nitro, and in which any two adjacent carbon atoms on the phenyl ring may optionally be joined by a carbon chain having 3 or 4 carbon atoms;
X1 is O or NH;
R1 and R2 are the same or different and are hydrogen or alkyl; and Z is a group SOnR8 or a group in which X2 is O, S or NR4;
R3 is alkyl, aryl, alkyloxy, aryloxy or NR5R6;
R4 is alkyl, aryl, alkyloxy, aryloxy, alkylthio, arylthio or NR5R6;
R5 and R6 are the same or different and are hydrogen, alkyl, aryl, COR7 or SO2R7;
R7 is alkyl, aryl, alkyloxy or aryloxy;
n is 1 or 2;
R8 is alkyl, aryl or NR9R10; and R9 and R10 are the same or different and are hydrogen, alkyl or aryl; provided that when Ar is unsub-stituted phenyl, R1 and R2 are H, X1 is NH, Z is and X2 is O, R3 is not methyl or an acid addition salt thereof; and provided that when Ar is 2,3-dimethylphenyl, R1 and R2 are hydrogen, Z is a group in which X2 is O, R3 is NR5R6 and R5 is hydrogen, then:

R6 is other than phenyl, substituted in the 4-position by Br, F, I, -NO2, -OR11, -CO2R11, -CONR12R13 or -SO2NR12R13, in which R11 is an alkyl group of from 1 to 18 carbon atoms, and each of R12 and R13 which may be the same or different, is hydrogen or an alkyl group of from 1 to 18 carbon atoms, and provided that when Ar is 2,3-dimethylphenyl, X1 is NH, R1 and R2 are hydrogen, Z is a group , in which X2 is O, R is NR5R6, and R5 is hydrogen, then:
R6 is other than phenyl substituted in the 4-position by Cl, CN or alkyl of 1 to 4 carbon atoms.

2. A compound as claimed in claim 1, wherein Ar is unsubstituted phenyl or substituted phenyl having one or more substituents which are the same or different and are alkyl or halogen.

3. A compound as claimed in claim 1, wherein Ar is substituted phenyl having one or more substituents which are the same or different and are alkyl or halogen.

4. A compound as claimed in claim 1, in which Ar is substituted phenyl wherein the substituents are selected from methyl and chloro.

5. A compound as claimed in claim 1, wherein Ar is disubstituted phenyl.

6. A compound as claimed in claim 1, wherein Ar is 2,3-dimethylphenyl.

7. A compound as claimed in claim 1, 2 or 3, wherein Z is said group .

8. A compound as claimed in claim 4, 5 or 6, wherein Z is said group .

9. A compound as claimed in claim 1, 2 or 3, wherein Z is a group .

10. A compound as claimed in claim 4, 5 or 6, wherein Z is a group .

11. A compound as claimed in claim 1, 2 or 3, wherein Z is .

12. A compound as claimed in claim 4, 5 or 6, ,wherein Z is .

13. A compound as claimed in claim 1, 2 or 3, wherein Z is a group in which R6 is aryl.

14. A compound as claimed in claim 4, 5 or 6, wherein Z is a group in which R6 is aryl.

15. A compound as claimed in claim 1, 2 or 3, wherein Z is a group wherein R6 is aryl.

16. A compound as claimed in claim 4, 5 or 6, wherein Z is a group wherein R6 is aryl.

17, A compound as claimed in claim 1, 2 or 3, wherein Z is a group , in which R6 is phenyl, 4-chlorophenyl, 4-cyanophenyl or .alpha.-naphthyl.

18. A compound as claimed in claim 4, 5 or 6, wherein Z is a group , in which R6 is phenyl, 4-chlorophenyl, 4-cyanophenyl or .alpha.-naphthyl.

19. A compound as claimed in claim 1, 2 or 3, wherein Z is a group in which R6 is phenyl, 4-chlorophenyl, 4-cyanophenyl or .alpha.-naphthyl.

20. A compound as claimed in claim 4, 5 or 6, wherein Z is a group in which R6 is phenyl, 4-chlorophenyl, 4-cyanophenyl or .alpha.-naphthyl.

21. A compound as claimed in claim 1, wherein Ar is phenyl.

22. 1-N-Phenylcarbamoyl-2-(2,3-dimethylphenoxymethyl)-2-imidazoline or an acid addition salt thereof.

23. 1-N-(.alpha.-Naphthyl)carbamoyl-2-(2,3-dimethylphenoxy-methyl)-2-imidazoline or an acid addition salt thereof.

24. 1-N-(4-Chlorophenyl)carbamoyl-2-(2,3-dimethyl-phenoxymethyl)-2-imidazoline or an acid addition salt thereof.

25. 1-N-(4-Cyanophenyl)carbamoyl-2-(2,3-dimethyl-phenoxymethyl)-2-imidazoline or an acid addition salt thereof.

26. A method of controlling arthropod pests which comprises applying to the pest or the pest's environment a compound of formula (I) as defined in claim 1.

27. A method as claimed in claim 26, wherein the compound is applied at a concentration of 0.001% to 20%, calculated by weight of the base.

28. A method as claimed in claim 26 or 27, wherein the pest is amember of the order Acarina.

29. A method according to claim 26 or 27, wherein said compound is 1-N-phenylcarbamoyl-2-(2,3-dimethyl-phenoxymethyl)-2-imidazoline, or an acid addition salt thereof.

30. A method according to claim 26 or 27, wherein said compound is 1-N-(.alpha.-naphthyl)carbamoyl-2-(2,3-dimethyl-phenoxymethyl)-2-imidazoline or an acid addition salt thereof.

31. A method according to claim 26 or 27, wherein said compound is 1-N-(4-chlorophenyl)carbamoyl-2-(2,3-dimethylphenoxymethyl)-2-imidazoline or an acid addition salt thereof.

32. A method according to claim 26 or 27, wherein said compound is 1-N-(4-cyanophenyl)carbamoyl-2-(2,3-dimethylphenoxymethyl)-2-imidazoline or an acid addition salt thereof.

33. A process for preparing a compound of formula (I) as defined in claim 1, or an acid addition salt thereof which comprises:-(a) reacting a compound of formula (II):- (II) wherein Ar, X1, R1 and R2 are as defined in claim 1, with an isocyanate, isothiocyanate, ketene, carbodiimide or a compound Z-X' where Z is as defined in Claim 1, and X' is a leaving group displaceable by a secondary amino group;
(b) reacting a compound of formula (V):- (V) wherein Ar, X1, R1 and R2 are as defined in claim 1, and Q is selected from the group consisting of imidate, ortho-ester, thioimidate, imidohalide, ester, amidine, thioamide, nitrile, carboxyalkylthioamide and carboxyl, with an ethylenediamine of formula (IV):-H2N.CH2CH2.NHZ (IV) where Z is as defined in claim 1;
(c) cyclisation of a compound of formula (VI):- (VI) wherein Ar, X1, R1, R2 and Z are as defined in claim 1, and W is oxygen or sulphur;
(d) reacting a compound of formula (VII) or an N- or O- metal salt thereof:

Ar-X1-H (VII) wherein Ar and X1 are as defined in claim 1, with a compound of formula (VIII):

(VIII) wherein R1, R2 and Z are as defined in claim 1, and V
is a leaving group selected from the group consisting of chloro, iodo, bromo, alkylsulphonyloxy and arylsulphonyloxy or (e) when Z in formula (I) is and R3 is alkoxy, aryloxy or NR5R6 reacting a compound of formula (IX):

(IX) wherein Ar, X1, X2, R1 and R2 are as defined in formula (I) and Y is a leaving group selected from the group consisting of halo, acyloxy, alkoxy, alkylthio, S-, SH, sulphonyloxy and carbalkoxy, with a compound of formula (X):-R"-H (X) wherein R" is alkoxy, aryloxy or NR5R6 where R5 and R6 are as defined in claim 1.

34. A process as claimed in claim 33(a) wherein the reaction is effected in water or an organic solvent.

35. A process as claimed in claim 33(a) or claim 34, wherein the reaction is effected in the presence of a base selected from an alkali metal hydroxide, an alkali metal carbonate or a tertiary organic base.

36. A process as claimed in claim 33(c), wherein the compound of formula (VI) is obtained from a compound of formula (V) as defined in claim 33(b), by reaction with a compound of formula (IV) as defined in claim 33(b).

37. A process as claimed in claim 33(e), wherein in the compound of formula (IX) X2 is R4N where R4 is as defined in claim 1, and Y is Hal where Hal is halogen and wherein the compound of formula (IX) is obtained by reaction of a compound of formula (II) as defined in claim 33(a) with a compound of formula (XII):-R4-N=C(Hal)2 (XII) where R4 is as defined in claim 1 and Hal is halogen.