Note: Descriptions are shown in the official language in which they were submitted.
~084922
The present invention relates to novel 2-cyclopropylamino-4-
formamidino_6-amino_s_triazine derivatives, to a process for
their manufacture and to their use in pest control.
The 2_cyclopropylamino-4-formamidino-6-amino-s-triazine
derivatives have the formula
~2 ~1
`~! .
,~,
N ~ I
N^CII-N ~ H ~ 5
wherein
Rl represents hydrogen, Cl-C4-alkyl which is unsubstituted
or substituted by lower alkoxy, or represents C3-C4-
alkenyl, C3-C4-alkynyl, cyclopropyl, hydroxyl, methoxy
or ethoxy,
R2 represents hydrogen, methyl or ethyl, or
Rl and R2 together with the nitrogen atom to which they are
attached represent a 5- or 6-membered heterocyclic ring
which can contain a further nitrogen atom or an oxygen
atam,
R3 represents methyl or ethyl,
R4 represents methyl or ethyl, and
R5 represents hydrogen or methyl.
- 2 -
, . -
.
, ' . ' , ' ~
~084922
Possible alkyl groups represented by Rl can be straight-chain
or branched, unsubstituted or substituted for example by low~r
alkoxy groups of 1 to 4 carbon atoms. Examples of such alkyl
groups include: methyl, ethyl, n-propyl, isopropyl, n-butyl,
isobutyl, sec. and tert butyl and 2-methoxyethyl. Examples of
possible C3-C4-alkenyl and C3-C4-alkynyl groups represented
by Rl include allyl and propargyl respectively.
Preferred compounds on account of their action are compounds
of the formula I in which Rl represents hydrogen, Cl-C4-alkyl
which is unsubstituted or substituted by lower alkoxy, or
represents C3-C4-alkenyl, C3-C4-alkynyl, cyclopropyl, hydroxyl,
methoxy or ethoxy, R2 represents hydrogen, methyl or ethyl, or
Rl and R2 together with the nitrogen atom to which they are
attached represent l-pyrrolidinyl, l_piperidinyl, 4-morpho-
linyl, l_piperazinyl, 1_(4_methyl)-piperazinyl or l-~midazolyl,
R3 represents methyl or ethyl, R4 represents methyl or ethyl
and R5 represents hydrogen or methyl.
Particularly advantageous compounds are those in wh~ch R
represents hydrogen, methyl, ethyl, isopropyl, 2_methoxy_
ethyl, allyl, propargyl or cyclopropyl, R2 represents hydro-
gen or methyl or Rl and R2 together with the nitrogen atom to
which they are attached represent l-pyrrolidinyl, 4-morpho-
linyl or l-im~dazolyl, R3 represents methyl, R4 represents
methyl and R5 represents hydrogen, and in which, if Rl re-
presents propargyl, R2 prefera~ly represents hydrogen.
.. . . . .
.
- ~
.
-
~084922
Compounds to be particularly highlighted are those in whichRl represents hydrogen, methyl or ethyl, R2 represents hydro-
gen, R3 represents methyl, R4 represents methyl and R5
represents hydrogen.
Particularly preferred compounds are:
2-cyclopropylamino-4-dimethylformamidino-6-amino-s-triazine,
2-cyclopropylamino-4-dimethylformamidino_6-ethyl~mino_s-
triazine,
2-cyclopropylamino-4-dimethylformamidino-6-methylamino-s-
triazine, and
2_cyclopropylæmino-4-dimethylformamidino-6-propargylamino_s_
triazine.
The compounds of the formula I are obtained by methods which
are known per se, for example by
(a) reacting a 2-cyclopropylamino-4,6-diamino_s-triazine of
the formula II
N N (II)
2N~ 11 NH~n5
in which Rl, R2 and R5 are as defined in formula I, with
.
. . ~ .
.
- ' ~ ' ' ~
- ,
084922
;! a carboxy amide acetal or kctal of the formula III
alkyl - O \ / R3
/ CH - N (III)
alkyl - O R4
in which R3 and R4 are as defined in formula I, or
(b) reacting a 2-cyclopropylamino-4-formamidino-6-chloro-s-
triazine of the formula IV
Cl
N N
/ N-CH-N ~ ~ N~ ~ (IV)
in which R3, R4 and R5 are as defined in fonmula I, with
ammonia or with a primary or secondary amine of the
formula V
HN'~ 1 (V)
R2
in which Rl and R2 are as defined in formula I.
The above reactions (a) and (b) are preferably carried out in
solvents or diluents which are inert to the reactants, for
example in aliphatic or aromatic hydrocarbons, halogenated
~084922
hydrocarbons, ethers or ethereal compounds or ketones.
Catalysts, for example p-toluenesulphonic acid, c~n be added
to the reaction mixture, but are not essential. The reaction
temperatures are between 30 and 130C.
The starting materials of the formulae II and IV can be
prepared ~n accordance with known processes by replacing
chlorine in chlorinated s-triazine deriva~ives by a correspon-
ding amino group or by several corresponding amino groups.
The manufacture of 2-diallylamino-4-amino-6-(N,N-dimethyl-
formamidine)_s_triazine is described in US patent specifi-
cation 3,073,851.
Diamino- and triamino-s-triazines are described as chemoste-
rilants for adult houseflies (~sca domestica) in US patent
specification 3,189,521. The chemosterilising action on
insects of 2,4,6-triamino-s-triazine derivatives (melamine
derivatives) is also described by S. Nagasawa et al.,
Botyu-Kagaku 39 (4), 105 (1974). A.B. Borkovec and A.B.DeMilo
[J.Med.Chem. 10 (5), 457 (1967)] and G.C. LaBrecque~R.L. Fye,
A.B. DeMilo and A.B.Borkovec lJ.Econ.Entomol. 61,(6), 1621 (196~)~
also describe the chemosterilising action of, inter alia, 2-
cyclohexylamino-4,6-diamino-s-triazine, 2-cyclohexylamino-4,6-
dihexylamino-s-triazine and 2,4,6-tris-cyclohexylamino-s-
triazine, and the salts thereof, on adult houseflies (Musca
domestica).
-- 6 --
~08~9ZZ
Surprisingly, it has now been found that the compounds of
the for~ula I possess a marked larvicidal action on insect
larvae, preferably on Diptera larvae. In contrast to the
above mentioned insecticidal chemosterilants, the compounds
of the formula I act on the developmental stages of the insects.
The actionconsistsin killingthe freshlyhatched larvae or preven-
~ing adults from hatching from the pupaeO The mode of action
of the compounds of the formula I is not to be compared with
that of classical insecticides, chemosterilants or juvenile
hormone analogues.
The active c pounds of the formula I can be used in parti-
cular for controlling hygiene pests and animal ectoparasites
of the order Diptera and of the families: Culicidae, Simulii-
dae, Tipulidae, Muscidae and Calliphoridae.
The compounds of the formula I can be used as pure active
substance or together with suitable carriers and/or additives.
Suitable carriers and additives can be solid or liquid and
correspond to the substances conventionally used in the art
of formulation, for example natural or regenerated substances,
solvents and/or dispersants. ~
The compositions according to the invention are manufactured
in known manner by homogeneously mixing and/or grinding
active substances (compounds) of the formula I with the
suitable carriers, with or without the addition of disper-
-` lQ~49ZZ
sants or solvents which are inert to the active substances.
The active substances may be processed to the following
formulations:
Solid formulations:
Dusts, tracking agents and granules (coated granules,
impregnated granules and homogeneous granules), premix
(feed additive).
~iquid formulations:
a) active substance concentrates which are dispersible
in water: wettable powders, pastes and emulsions;
b) solutions: sprays (aerosols).
To manufacture solid forms (dusts, tracking agents), the
active substances are mixed with solid carriers. Suitable
carriers are, for example: kaolin, talc, bolus, loess, chalk,
limestome, ground limestone, attaclay, dolomite, diatomaceous
earth, precipitated silica, alkaline earth silicates, sodium
and potassium aluminium silicates (feldspar and mica),
calcium and magnesium sulphates, magnesium oxide, ground
synthetic materials, fertilisers, for example ammonium
sulphate, ammonium phosphate,~ammonium nitrate, urea, ground
vegetable products, such as corn meal, bark ~ust, sawdust,
nutshell meal, cellulose powder, residues of plant extrac-
tions, activated charcoal etc. These substances can either
be used singly or in admixture with one another.
-- 8 --
:~08~9Z2
Granules can be very easily manufactured by dissolving an
active substance of the formula I in an organic solvent and
applying the solution thereby obtained to a granulated
mineral, for example attapulgite, SiO2, granicalcium,
bentonite etc. and then evaporating the solvent.
Polymer granules can also be manufactured by mixing the
active substances of the formula I with polymerisable
compounds (urea/formaldehyde; dicyandiamide/formaldehyde;
melamine/formaldehyde or others), whereupon a mild poly-
merisation is carried out that does not affect the active
substances and in the process of which the granulation is
carried out during the gel formation. It is more advantageous
to impregnate finished, porous polymer granules (urea/
formaldehyde, polyacrylonitrile, polyester or others) which
have a specific surface area and a favourable predeterminable
adsorption/desorption ratio, with the active substances, for
example in the form of their solutions (in a low boiling
solvent) and to remove the solvent. Polymer granules of this
kind in the form of microgranules having preferably a bulk
density of 300 g/litre to 600 g/litre can also be manufactured
with the aid of ~tomisers.
It is also possible to obtain granules by compacting the
carrier with the active substance and additives and subsequent-
ly comminuting the product.
~08~92Z
To these mixtures can also be added additives which stabilize
the active substance and/or nonionics, anionics and
cationics, which, for example, ensure a better wettability
(wetting agents) and dispersibility (dispersants). Examples
of suitable substances are: olein/chalk mixture, cellulose
derivatives (methyl cellulose, carboxymethyl cellulose),
hydroxyethyl glycol ethers of monoal~yl and dialkyl phenols
having 5 to 15 ethylene oxide radicals per molecule and 8 to
9 carbon atoms in the alkyl moiety, ligninsulphonic acid, the
alkali metal and alkaline earth metal salts thereof, poly-
ethylene glycol ethers (carbowaxes), fatty alcohol poly-
ethylene glycol ethers having 5 to 20 ethylene oxide radicals
per moiecule and 8 to 18 carbon atoms in the fatty alcohol
moiety, condensation products of ethylene oxide, propylene
oxide, polyvinylpyrrolidone,polyvinyl alcohol, condensation
products of urea and formaldehyde, and also latex products.
Water-dispersible concentrates, i.e. wettable powders, pastes
and emulsifiable concentrates, are compositions which can be
diluted with water to the desired concentration. They consist
of active substance, carrier, optionally additives which
stabilize the active substancè, surface-active substances and
anti-foams and, if appropriate, solvents.
Wettable powders and pastes are obtained by ~ixing and grin-
ding the active substances with dispersants and pulverulent
carriers in suitable devices until homogeneity is attained.
- 10 _
1(~849Z2
Suitable carriers are, for example, those already mentioned
for the solid forms of application. In some cases it is
advantageous to use mixtures of different carriers. Examples
of dispersants are condensation products of sulphonated
naphthalene and sulphonated naphthalene derivatives with
formaldehyde, condensation products of naphthalene or
naphthalene sulphonic acids with phenol and ~ormaldehyde as
well as alkali metal, ammonium and alkaline earth metal salts
of ligninsulphonic acid, in addition, alkylaryl sulphonates,
alkali metal and alkaline earth metal salts of dibutyl-
naphthalenesulphonic acid, fatty alcohol sulphates such as
salts of sulphated hexa-decanols, heptadecanols, octadecanols,
and salts of sulphated fatty alcohol glycol ethers, the
sodium salt of oleyl methyl tauride, ditertiary ethylene
glycols, dialkyl-dilaurylammonium chloride and fatty acid
alkali metal and alkaline earth metal salts.
Suitable anti-foams are for example silicone oils
The active substances are so mixed, grDund,sieved and strained
with the additives mentioned above that, in wettable powders,
the solid particle size of 0.02 to 0.04 mm and in pastes, of
0.03 m~, is not exceeded. Emulsifiable concentrates and pastes
are manufactured by using dispersants, such as those referred
to above, organic solvents, and water. Examples of suitable
solvents are: alcohols, dimethyl sulphoxide, and mineral oil
- 11 _
~0849ZZ
fractions which boil between 120 and 350C. The solvents
must be virtually odourless and inert to the active sub-
stances.
Furthermore, the compositions according to the invention can
be applied in the form of solutions. For this purpose the
active substances or several active substances of the general
formula I are dissolved in suitable organic solvents or
mixtures of solvents. Aliphatic and aromatic hydrocarbons,
chlorinated derivatives thereof, alkylnaphthalenes and
mineral oils, singly or in admixture, can ~e used as organic
solvents.
Formulations of the novel active compounds of the formula I
are described hereinafter. The parts denote parts by weight.
Dusts:
The following substances are used to manufacture a) a 0.5%
and b) a 2% dust:
a) 0.5 part of active substance
99.5 parts of talc
b) 2 parts of active substance
1 part of highly disperse silicic acid
97 parts of talc.
The active substances are mixed with the carriers and ground.
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-
:~084922
Tracking Agents:
5 parts of active substance are mixed with
95 parts of carbonate of lime and ground to an average
particle size of 80~.
Granules:
5 parts of active substance are dissolved in a solvent,
e.g. methylene chloride, and mixed with
2 parts of polyethylene glycol ("Carbowax").
91.5 parts of calcium carbonate are impregnated with the
mixture and
1.5 parts of precipitated silicic acid are admixed.
The solvent is subsequently evaporated.
Wettable Powder:
50 parts of active substance are mixed with
5 parts of a dispersing agent, e.g. sodium lignin-
sulphonate,
5 parts of a wetting agent, e.g. dibutylnaphthalene-
sulphonic acid
10 parts of silicic acid and
30 parts of China clay
and the mixture is finely ground.
_ 13 -
iO849Z~
Emulsifiable Concentrate:
20 parts of active substance are mixed with
20 parts of emulsifier, e.g. a mixture of alkylarylpoly-
glycol ether with alkylarylsulphonates, and
60 parts of solvent
until the solution is completely homogeneous. By
diluting this concentrate with water it is possible to
obtain an emulsion of the desired concentration.
Premix (feed additive):
0.25 parts of active substance and
4.75 parts of secondary calcium phosphate, or ~hina
clay, aerosil or carbonate of lime are homogeneously
mixed with
95 parts of an animal feed, e.g. poultry food.
Spray:
The following constituents are used to manufacture a 2% spray:
2 parts of active substance
98 parts of kerosene.
Other biocidal active substances or agents can be admixed
with the compositions described hereinabove Thus in addition
to the cited compounds of the general formula I, the composi-
tions of the present invention can obtain; for example,
insecticides to broaden the activity spectrum.
_ 14 -
~08492Z
The compositions, or the active compounds contained therein,
exert their inhibitory action therefore chiefly on the deve-
lopment of larvae or pupae of insects, preferably of the
order Diptera.
Example 1
2-Cyclopropyl.amino-4-N',N'-dimethylformamidino-
_morDholino-s-triazine
.
20 g of 2-cyclopropylamino-4-amino-6-morpholino-s-triazine
are suspended in 200 ml of benzene and the suspension is
treated with 13 g of N,N-dimethylformamide-dimethyl acetal
with the addition of 0.5 g of p-toluenesulphonic acid (as
catalyst). The reaction mixture is refluxed for 10 hours. The
solvent is then removed in vacuo and the residue is suspended
in ether. The precipitated solid is recrystallised from iso-
propanol Melting point: 160-162C.
The following compounds are prepared in accordance with the
above procedure:
~.0849Z2
No. Compound mp. in C
1 2-cyclopropylamino-4-N',N'-dimethylforma- 152-153
midino-6_pyrrolidino-s-triazine
2 2-cyclopropylamino_4-N',N'-dimethylforma- 169-170
midino 6-ethylamino-s-triazine
3 2_cyclopropylamino_4-N',N'-dimethylforma- 186-188
midino-6-methylamino-s-triazine
4 2-cyclopropylamino-4-N',N'-dimethylforma 158-lS9
midino-6-allylamino-s-triazine
2-cyclopropylamino_4_N',N'-dimethylforma- 193-194
midino-6-isopropylamino-s_triazine
6 2-cyclopropylamino-4-N',N'-dimethylforma- 126
midino-6_propargylamino-s_triazine
7 2,6-bis-(cyclopropylamino)_4_N',N'-dimethyl- 220-223
formamidino-s-triazine
8 2-cyclopropylamino-4-N',N'-dimethyl- 184-185
formamidino-6-imidazolo-s-triazine
9 2-cyclopropylamino-4-N',N'-dimethyl- 151-153
formamidino_6-(2-methoxyethylamino)-s-triazine
2-cyclopropylamino-4-N',N'-dimethylforma- 132-134
midino-6-dimethylamino-s-triazine
11 2-cyclopropylamino-4-N',N'-dimethylforma- 96-98
midino-6-(N-methyl-N-ethylamino)-s-triazine
12 2-cyclopropylamino-4-N',N'-dimethylforma- 196-198
midino-6-amino-s-triazine
- 16 -
~084922
Example 2
Action against Musca domestica
50 g of freshly prepared CSMA nutrient substrate for maggots
are charged into beakers, 2,5 ml portions of a 1% acetonic
solution of the respective active substance are pipetted onto
the nutrient substrate present in the beakers. The substrate
is then thoroughly mixed and the solvent subsequently allowed
to evaporate.
Then 25 one-, two- and three- day-old maggots and approx. 50
eggs of Musca domestica are put into each of the beakers
containing the treated nutrient substrate for
testing with each active substance,
After the maggots have pupated, the pupae are separated from
the substrate by flushing them out with water and counted,
The number of flies which have hatched out of the pupae is
then counted after 10 days and any influence on the meta-
morphosis thereby determined.
The compounds of the formula I displayed good activity in
this test,
10849ZZ
Example 3
_ction against Lucilia sericat
1 ml of an aqueous solution containing 0.5% of active
substance is added to 9 ml of a culture medium at 50C. Then
approx. 30 freshly hatched larvae o Lucilia sericata are
added to the culture medium and the insecticidal action is
determined by evaluation of mortality after 48 and 96 hours
respectively. In this test, the compounds of the formula I
act well against Lucilia sericata.
Example 4
Action against Aëdes aegypti
Active substance concentrations of 10, 5 and 1 ppm respecti-
vely are obtained by pipetting a specific amount of a 0.1%
solution of the active substance in acetone onto the surface
of 150 ml of water in each of a number of beakers. After the
acetone has evaporated, 30 to 40 two-day-old larvae of Aëdes
aegypti are put into each of the beakers containing the
active substance solution~ Evaluation of mortality is made
after 1, 2 and 5 days respectively.
In this test, the compounds of the formula I exhibit good
action against Ae'des aegypti.
.
