IMIDAZOLINES

IMIDAZOLINES

English Abstract

ABSTRACT
Compounds of formula (I):
<IMG> (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 <IMG> 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;

A528
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 <IMG> and X2 is O, R3 is not methyl,
methods of making such compounds, pesticidal formulations
containing them and their use as pesticides are disclosed.

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):
<IMG> (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 <IMG> 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
27

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 <IMG>
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 <IMG> 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 <IMG> , 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.
28

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 <IMG>.
8. A compound as claimed in claim 4, 5 or 6, wherein
Z is said group <IMG>.
29

9. A compound as claimed in claim 1, 2 or 3, wherein
Z is a group <IMG>.
10. A compound as claimed in claim 4, 5 or 6, wherein
Z is a group <IMG>.
11. A compound as claimed in claim 1, 2 or 3, wherein
Z is <IMG>.
12. A compound as claimed in claim 4, 5 or 6, ,wherein
Z is <IMG>.
13. A compound as claimed in claim 1, 2 or 3, wherein
Z is a group <IMG> in which R6 is aryl.
14. A compound as claimed in claim 4, 5 or 6, wherein
Z is a group <IMG> in which R6 is aryl.
15. A compound as claimed in claim 1, 2 or 3, wherein
Z is a group <IMG> wherein R6 is aryl.
16. A compound as claimed in claim 4, 5 or 6, wherein
Z is a group <IMG> wherein R6 is aryl.
17, A compound as claimed in claim 1, 2 or 3, wherein
Z is a group <IMG> , 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 <IMG>, 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 <IMG> 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 <IMG> 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.
31

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):-
32

<IMG>
(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):-
<IMG>
(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):-
33

<IMG> (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):
<IMG> (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 <IMG> and R3 is
alkoxy, aryloxy or NR5R6 reacting a compound of formula
(IX):
34

<IMG> (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.
36

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)
12
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 )
12
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
NH2
-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)
1 2
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
~ .,
- 12 -
'`

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.
- 13 -
,
~ ~ .

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
- 14 -
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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.
EXAMPLE 1
, .
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%.
EXAMPLE 2
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
- 15 -
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.
. :
.
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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%.
EXAMPLE 3
_
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):-
- 16 -
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-: :
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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
EXAMPLE 4
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.
EXAMPLE 5
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.
EXAMPLE 6
1~ l-N-Methyloxycarbonyl-2-(2,3-dimethylphenoxy-
methyl)-2-imidazoline, m.p. 120C.
EXAMPLE 7
,,
l-N-Methylcarbamoyl-2-(2,3-dimethylphenoxy-
methyl)-2-imidazoline, m.p. 147-150C. (dec.).
EXAMPLE 8
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.
EXAMPLE 10
l-N- (a -Naphthyl)carbamoyl-2-(2,3-dimethyl-
phenoxymethyl)-2-imidazoline, m.p. 156-158C.
- 18 -
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EXAMPLE 11
.
l-N-(4-Chlorophenyl)carbamoyl-2-(2,3-dimethyl-
phenoxymethyl)-2-imidazoline, m.p. 132C.
EXAMPLE 12
l-N-(4-Cyanophenyl)carbamoyl-2-(2,3-dimethyl-
phenoxymethyl)-2-imidazoline, m.p. 172-174C.
EXAMPLE 13
l-N-Phenylcarbamoyl-2-phenoxymethyl-2-imidazoline,
m.p. 170C.
EXAMPLE 14
l-N,N-Diphenylcarbamoyl-2-(2,3-dimethylphenoxy-
methyl)-2-imidazoline, m.p. 143-145C.
EXAMPLE 15
l-N-~-Tolycarbamoyl-2-(2,3-dimethylphenoxy-
methyl)-2-imidazoline, m.p. 137C.
EXAMPLE 16
l-N-Phenylcarbamoyl-2-(a-phenyloxyethyl)-2-
imidazoline, m.p. 159C.
EXAMPLE 17
1-N-(~-Naphthyl)carbamoyl-2-phenoxymethyl-2-
imidazoline, m.p. 160-163C.
EXAMPLE 18
l-N-Cyclohexylcarbamoyl-2-(2,3-dimethylphenoxy-
methyl)-2-imidazoline, m.p. 63C.
EXAMPLE 19
l-N-Phenylcarbamoyl-2-(2-chloroanilinomethyl)-2-
imidazoline, m.p. 169~C.
EXAMPLE 20
l-(N-Phenyl-N-methyl)carbamoyl-2-(2,3-dimethyl-
phenoxymethyl)-2-imidazoline, m.p. 112C.
-- 19 --
. : ~

2~
EX~NPLE 21
l-~-Phenylcarbamoyl-2-(~,~-dimethylphenoxy-
methyl)-2-imidazoline, m.p. 81-85C.
EXAMPLE 22
l-N-Hexadecylcarbamoyl-2-(2,3-dimethylphenoxy-
methyl)-2-imidazoline, m.p. 76-77C.
EXAMPLE 23
l-~-(~-Naphthyl)carbamoyl-2-(3-methylanilino-
methyl)-2-imidazoline, m.p. 146C.
EXAMPLE 24
l-~-Phenylcarbamoyl-2-(2-chloroanilinomethyl)-
2-imidazoline, m.p. 168-169C.
EXAMPLE 25
1-~-(2,6-Dimethylphenyl)carbamoyl-2-(2,3-dimethyl-
phenoxymethyl)-2-imidazoline perchlorate salt, m.p. 221-
222C
EXAMPLE 26
l-N-(2,3-Dichlorophenyl)carbamoyl-2-(2,3-dimethyl-
phenoxymethyl)-2-imidazoline, m.p. 175-180C.
EXAMPLE 27
l-N-Phenylcarbamoyl-2-(3-methoxyphenoxymethyl)-
2-imidazoline, m.p. 101C.
EXAMPLE 28
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
20 -
- ~ . .. .
'::: .: :
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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.
EXAMPLE 29
By a method analogous to that used in Example 28,
l-benzenesulphonyl-2-(2,3-dimethylphenoxymethyl)-2-
imidazoline, m.p. 108-110C, was prepared.
EXAMPLE 30
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.
- 21 -
. .
.

(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.
EXAMPLE 31
.
; 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-
- 22 -
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:

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.
TABLE 1
; ~
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%
EXAMPLE 32
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.
- 23 -
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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.
FORMULATION 1
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 -
,

FORMULATION 4
Pour-On
Active Compound 5.0 parts by wt.
Dimethyl Formamide85.0
Castor Oil 10.0 "
100. 0
FORMULATION 5
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 -
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