Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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DESCRIPTION
"ALKYLPHOSPHONOTHIOATE INSECTICIDES AND NEMATOCID~S
AND INTERMEDIATES THEREFOR"
This invention relates to 0-alkyl and 0-aryl
S-(tertiary alkyl) alkylphosphonothioate compounds,
their preparation/ insecticidal and nematocidal
compositions containing them and intermediates for
their preparation~
Certain alkylphosphonothioate insecticides are
described in the prior art, for example, in U.S. Patent
No. 3,209,020. However, none of the species described in
that patent or in other known prior art possess a tertiary
alkyl group attached to the sulphur atom.
It has now been found -that certain S-tertiary
alkyl compounds possess particularly useful insecticidal
or nemat~cidal activity.
The present invention accordingly provides
compounds of -the general formula:-
O ~ ORl
R - P (I)
SR2
wherein R represents alkyl of 1 to 8 carbon atoms, haloalkyl
of 1 to 8 carbon atoms, alkenyl OI 2 to 8 carbon atoms,
haloalkenyl of 2 to 8 carbon atoms, alkynyl of 2 to 8
carbon atoms, or haloalkynyl of 2 to 8 carbon atoms,
4~7~
Rl represents alkyl of 1 to 8 earbon atoms or aryl and
R2 represents tertiary alkyl of 4 to 8 carbon atoms, which
exhibit a wide range of inseetieidal and nematoeidal
activity and are of particular interest in controlling
eorn rootworm (Diabrotiea sp) beeause of their excellent
activity against this pest and their long residual soil
activity.
It is to be understood that, in this speeifieation
and the accompanying claims, unless otherwise indicated,
alkyl groups and moieties may be straight- or branched-chain.
In general formula I:
R preferably represents alkyl of 1 to 4 carbon
atoms, especially methyl or ethyl;
Rl preferably represents alkyl of 1 to 4 carbon
atoms (compounds in which Rl represents phenyl or phenyl
substituted by one or more (preferably one) atoms or
radicals selected from the group consisting of alkyl of
1 to 4 carbon atoms (preferably methyl), alkoxy of 1 to
4 carbon atoms (preferably methoxy)~ alkylthio of 1 to
4 carbon atoms, alkylsulphinyl of 1 to 4 carbon atoms,
alkylsulphonyl of 1 to 4 carbon atoms, chlorine, bromine,
fluorine, nitro, cyano and trifluoromethyl, are also
preferred); and
R2 preferably represents tert-butyl or tert-amyl.
Particularly preferred compounds of general
formula I are those in which R represents methyl or ethyl,
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Rl represents alkyl of 1 to 4 carbon atoms and R2 represents
t-butyl or t-amyl. Other particularly preferred compounds
are those in which R represents methyl or ethyl, Rl
represents phenyl or phenyl substituted by a chlorine or
fluorine atom, or by a methyl, methoxy or trifluoromethyl
group and R2 represents t-butyl or t-amyl.
The compounds of general formula I can be prepared
by the application of known methods. By the expression
"known methods" as used in this specification is meant
methods heretofore used or described in the literature.
According to a feature of the invention the
compounds of general formula I are prepared by the process
which comprises reacting an S-alkyl alkylphosphonothioic
halide of the general formula:-
O X
R - P / (II)
SR2
wherein R and R2 are as hereinbefore defined and X
represents a halogen atom, preferably chlorine, with an
alcohol or phenol of the general formula RlOH, wherein R
is as hereinbefore defined,in the presence of a base.
The process proceeds in accordance with the
reaction scheme~
o / x 1l / ORl
R - P + RlOH base R - P + base . HX
~II) SR2 2
wherein R, Rl, R2 and X are as hereinbefore defined.
rme reaction is advantageously carried out at a
temperature of about 0C to 100C in an organic solvent
in the presence oi a tertiary amine, or an alkali metal
salt of the alcohol or the phenol ~lOH, prepared from
the alcohol or phenol and an alkali metal such as sodium.
Suitable organic solvents are, for example,
benzene, toluene, cyclohexane and 2-butanone, or an
alcohol RlOH.
Suitable tertiary amines include trirnethylamine,
triethylamine, dimethylaniline, diethylaniline and pyridine.
rme S-alkyl phosphonothioic halides of general
formula II wherein R1, R2 and X are as hereinbefore defined
also constitute a feature of the present invention.
r~he synthesis of S~alkyl alkylphosphonothioic
halides is usually accomplished by methods o-ther than the
direct addition of thiols to alkylphosphonic dihalides
because direct reaction is normally accompanied by an
undesirable side reaction in which both halogen atoms in
the phosphonic dihalide are substituted by an alkyl thiol.
r~he side reaction is a particular problem when normal
alkyl thiols are used. Thus, when the synthesis of normal
S-alkyl alkylphosphonothioic chlorides is desired,
alternative routes are selected.
It has been discovered that tertiary alkylthiols
reac-t smoothly with alkylphosphonic dihalides to give mono
addition of one thiol in good yield, according to the
following equation:
/ solvent ll / X
5 RP + HSR2 + base ~ RP + base.HX
\X \ S~2
III
wherein R, R2 and X are as hereinbefore defined . According
to a feature of the present invention, the compounds of
general formula II are prepared by reacting a compound of
the general formula III wherein R and X are as hereinbefore
defined with a compound of the general formula R2$H, ~Iherein
R2 is as hereinbeiore defined, in a solvent, in -che presence
of a base, at a temperature of about 20C to 100C. In
the compounds of general formula II, preferably R represents
alkyl of 1 to 4 carbon atoms, particularly methyl or ethyl;
preferably R2 represents tert-butyl or tert-amyl, and
preferably X represents chlorine.
Suitably the reaction is carried out in an organic
solvent, in the presence of a tertiary amine such as
trimethylamine, triethylamine, pyridine, dimethylaniline
or diethylaniline.
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Suitable organic solvents, which are preferred,
include benzene, toluene, cyclohexane, acetone and
2-butanone.
Generally, the reaction is conducted at a
temperature of about 20C to lOO~C, but the temperature
is not critical except insofar as it is sufficient to make
the reaction proceed at a reasonable rate and is not
excessive. It has been found advantageous to add the
tertiary amine to the other reactants at a temperature
of about 20C to 30C and then to heat the entire reaction
mixture to a temperature of about 70C to 80C to complete
the reaction.
The reaction is normally carried out with an
approximately equal molar ratio of the alkyl phosphonic
dihalide, thiol and the base. An excess of about 10 to
20% of the alkylphosphonic dihalide can be used relative
to the other reactantsO ~Iowever, the use of a sli~ht
excess of the thiol and the base relative to the
alkylphosphonic dihalide (5-10/~ excess) did not appreciably
affect the yield~
Particularly preferred compounds of general
formula II are S-tert~butyl ethylphosphonothioic chloride,
S-tert-amyl ethylphosphonothioic chloride, S-tert-butyl
methylphosphono'chioic chloride, and S-tert-amyl methyl-
phosphonothioic chloride which are used as intermediatesin the following Examples 1 to 16.
The following Exarnples illustrate the
preparation of compounds of general formulae I and II and
the pesticidal properties of the former.
EXAMPLE 1
S-tert-Butyl ethylp_osphonothioic chloride
0 Cl
11/
CH3CH2 P \ IH3
s f CH
CH3
To a solution o~ ethylphosphonic dichloride (32.0 g,
0022 mol) in 300 ml toluene, was added 2-methyl-2-
propanethiol (18 g, 0.2 mol). ~hile stirring,triethyl-
amine (22 g, 0.22 mol) was added dropwise; the temperature
of the reaction mixture was maintained at 30-35C during
the addition of the amine. After addition of the amine
the mixture was stirred overnight at room temperature.
The amine hydrochloride which precipitated was filtered
off and the toluene solution was concentrated under vacuum.
Hexane (200 ml)- was added and the solution obtained was
filtered.
The solvents were stripped off under vacuum
and the residual liquid was distilled. The product (25 g,
72.5% yield) di.stilled at 72-73C/007 mmHg. Proton
magnetic resonance spectroscopy in deuterochloroform
(CDC13) with Si(Me)4 as reference confirmed the structure
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of the title compound.
EXAMPLE 2
Preparation of 0-ethyl-S-tert-butyl ethylphosPhonothioate
To a solution of S-tert-butyl ethylphosphonothioic
chloride (obtained as described in Example 1) (8.0 g,
0.048 mol) in toluene (50 ml) was added a solution of sodium
ethoxide (0.04 mol) in ethanol (40 ml). The addition was
carried out dropwise, with stirring under a nitrogen
atmosphere. Stirring was continued overnight at room
temperature, and then approximately 80% of the solvents were
removed under vacuum. Toluene (100 ml) was added and the
sodium chloride formed from the reaction was filtered off.
Toluene was stripped off under vacuum and the residual
liquid was distilled. The product (5.8 g, 69.6% yield)
distilled at 69-72C/0,2 mmHg.
Analysis of the proton magnetic resonance spectrum
of this product confirmed the structure of the title
compound.
EXAMPLE 3 to 6
In a manner analogous to that of Example 2, the
following compounds were prepared.
1l /OR
R - P \
SR2
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Example R Rl R2 B.p.C/mmH~.
C2H5 CH3 t-butyl 64-67/0.7
l~ C2H5 C3H7 t-butyl 61-63/0,05
2 5 (CH3)2CH t-butyl 42-43/0.05
6 C2H5 C2H5 t-amyl 56-58/0.07
EXAMPLE 7
Preparation of 0-phenyl-S-ter_-butyl ethylphosphonothioate
O /=\
11/~
2 5 \ 1 3
CH3 CH3
To a solution of S-text-butyl ethylphosphonothioic
chloride (5 g, 0.025 mol), and phenol (2.35 g, 00025 mol)
in acetone (20 ml), was added, in one portion, triethylamine
(2.5 g, 0.025 mol); the mixture was stirred overnight under
nitrogen at room temperature. The reaction mixture was then
diluted with toluene (100 ml) and washed once with 5% w/v
sodium hydroxide solution, and twice with water. The
solution was dried over anhydrous sodium sulphate and the
solvent was stripped off under vacuum. The residual liquid
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was subjected to high vacuum (0.2 mmHg) at 60C for
15 minutes to yield the desired product as confirmed
by its proton magnetic resonance spectrum in deutero-
chloroform (CDC13) with Si(Me)4 as reference.
EXAMPLES 8 to 15
... . . .
In a manner analogous to that of Example 7,
the following compounds were prepared.
1 ~ ~1
R - P
SR2
Æxample R R R
_ 1 2
2H5 o-methyl-phenyl tert-butyl
C2H5 p-chloro-phenyl L ert-butyl
C2H5 phenyl tert--amyl
11 C2~5 m-trifluoromethyl- tert-amyl
phenyl
12 C2H5 p-fluoro-phenyl tert-amyl
13 C2H5 p-chloro-phenyl tert-amyl
14 C2H5 o-chloro-phenyl tert-amyl
CH3 phenyl tert-amyl
EXAMPLE 16
Meta-cresol (4.6 g) was dissolved in acetone
(100 ml) and potassium carbonate was added. The mixture
was stirred at room temperature for 30 minutes, and
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S-tert-but~l methylphosphonotllio;c chloride (7~5 g)
was l:hen aclded.
Stirring was continued overnight, and the
~olution was then filtered and the solvent evaporated.
Water (100 ml) was added and the mixture extracted with
diethyl ether (100 ml)O The ethereal extract ~as was~ed
once with 5% w/v potassium hydroxide solution, then
~ with water and was finall~ dried and evaporated to give
4.0 g of 0-3-tolyl-S-tert-butyl methylphosphonothioate.
The product was identified by its proton magnetic
resonanc~ spectrum. Its purity is higher than 90%~
EX~MPLE 17
Testing for corn rootworm intrinsic activity,
and activity against Southern Armyworm.
A. Corn ~ootworm Intrinsic Activi ~ ~CRW?
. _ _
Ihe test compound is prepared as a one percent
w/v stock solu-tion with acetone or ethanol. Ihe stock
solution is then diluted with an aqueous solution o~
Tween-20 (500 ppm) and water to the appropriate
concentration (i.e. 500, 100, 1, 0.1 or 0.05 ppm o~ test
compound). Two ml of the test solution is pipetted into
a 9 cm petri dish containing two layers o~ ~ilter paper.
Second instar larvae are introduced and the dish closed~
Observations ~or mortality and moribund larvae are made
after two days (48 hours~ exposure. Insecticidal activity
is primarily ~y contact and vapour action with minimal
ingestion.
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B. Southern Arm~torm Intrinsic ~ctivity (SAW~
Stock solution (1% w/v) of test compound in
acc~one was pxepared and dilu-ted to the desired
concentration using a 500 ppm ~ween-20 aqueous solution~
Lima bean leaves are dipped into the solution and
transerred to petri dishes (100 x 15 mm) each containing
two filter papers moistened with 2 ml water, Each petri
dish contained one leaf and was left open to dry out the
solution on the leaf. Five third instar larvae of
Southern Arm~torm ~Spod~ptera eridania) were added to
the lea* and the dish was finally covered.
The dishes were kept at 78F for 72 hours and
percentage kill was recorded.
Ihe results of Tests ~ and B are tabulated in
Table 1 which shows the percentage kill obtained using
compounds prepared in the indicated Exa~ples.
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TABLE 1
% Kill
C R W S A W
~te in ppm . _ . _ .
\ 1 0.1 0. ~5 5001.00
Example N~ . . _
2 100 95 75 100100
3 100 100 100 10090
L~ 100 70 _ 10015
L~5 _ 80 ~5
6 100 95 100 10050
7 100 100 90 10095
8 100 100 15 100100
9 100 35 40 10095
100 100 70 10080
11 100 100 85 10080
12 100 100 90 10060
13 100 85 55 10075
14 95 95 15 10080
16 100 100 100 _
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These results show the excellent insecticidal
activity of the compounds according to the invention which
can be used for combatting numerous insects such as
coleoptera (e.g~ Diabrotica sp) or corn rootworm and
lepLdoptera.
For use in practice, the compounds of general
formula I are generally employed in the form of
compositions, which also constitute a feature of -the
invention, and which generally comprise, in addition to
the active compound of general formula I, at least one
agriculturally acceptable carrier and/or surface-ac~ive
agent. The proportion of active ingredient in these
compositions is generally from 0.001% to about 95% by
weight: the proportion of surface active agent is generally
from O to 20% by weight.
In the present specification, the term "carrier"
denotes an organic or inorganic, natural or synthetic
material with which the active ingredient is associated
in order to facilitate its application to the plants or to
the soil. The carrier can be solid (e.g. clays, natural
or synthetic silicates, silica, resins, waxes and solid
fertilisers) or liquid (e.g. water, alcohols, petroleum
fractions, aromatic or paraffinic hydrocarbons, chloro-
hydrocarbons and liquefied gases).
~2~
The surface-active agent can be an emulsifying,
dispersing, deflocculating or wetting agent of the iOIliC
or non-ionic type. Examples which may be mentioned are
salts of polyacryl.ic acids, salts of lignosulphonic acids,
salts of phenolsulphonic or naphthalenesulphonic acids,
condensates of ethylene oxide with fatty alcohols, fatty
acids or fatty amines, substituted phenols tin particular
alkylphenols or arylphenols), salts of sulphosuccinic acid
est~rs, taurine derivatives (in particular alkyltaurates),
and phosphoric acid esters of condensates of ethylene oxide
with alcohols or with phenols.
The compositions can also contain other
ingredients, e.g. thickeners, thixotropic agents, protective
colloids, adhesives, penetrating agents and stabilisers,
and also other known active ingredients having pesticidal
properties (in particular herbicidal, fungicidal and
insecticidal properties), properties which assist plant
growth (in particular fertilisers) or properties which
regulate plant growth. More generally, the compounds
according to the invention can be combined with any of the
solid or liquid additives used in the customary techniques
for the preparation of pesticidal compositions.
The compositions according to the invention can
be prepared in the form of wettable powders, dusting
powders, granules, solutions, emulsifiable concentrates,
emulsions, suspension concentrates and aerosols.
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The wettable powders, or spraying powders, usually
contain Erom 20 to 95% by weight o:E active ingredient and
g~ne~all~ contain, in addition to a solid carrier, from
0 to 5% by weight of wetting agent, and from 0 to 10% by
weight of one or more stabilisers and/or other additives,
such as penetrating agents, adhesives or anti-caking agents
and dyestuffs.
They are prepared by mixing the constituents in
mixers and by grinding them in mills or other suitable
grinders, e.g. air grinders, so as to obtain the desired
particle size.
The composition of an 80% w/w wettable powder
according to the invention is given below by way of example
(in the following Examples percentages are by weight):
EXAMPLE 18
active ingredient 80%
sodium alkylnaphthalenesulphonate 2%
sodium lignosulphonate 2%
anti-caking silica 3%
20 kaolinite 13%
Another example of a wettable powder according
to the invention is given below:
EXAMPLE 19
active ingredient 50%
sodium alkylnaphthalenesulphonate 2%
low-viscosity methylcellulose 2%
diatomaceous earth 46%
lZZ4~
Another example of a wettable powder according
to the invention is given below:
EXAMPLE 20
active ingredient 90%
5 sodium dioctylsulphosuccinate 0.2%
synthetic silica 9~%
Granules, which are intended to be placed on
the soil, are usually prepared so that they have dimensions
of between 0.1 and 2 mm, and they can be manufactured by
agglomeration or impregnation. In general, the granules
will conkain from 0.5 to 25% of active ingredient and
from 0 to 10% by weight of additives, such as stabilisers,
slow-release modifiers, binders and solvents.
Emulsifiable concentrates, which can be applied,
after dilution, by spraying, usually contain from 10 to
50% by weight/volume of active ingredient. In addition
to the active ingredient and the solvent, they can also
contain, if necessary, from 2 to 20% by weight/volume of
an emulsifying agent and from 2 to 20% by weight/volume of
suitable additives, such as surface-active agents,
stabilisers, penetrating agents, corrosion inhibitors,
dyestuffs and adhesives.
Suspension concentrates, which can also be
applied by spraying, are prepared so as to give a stable
fluid product which does not settle out, and they usually
contain from 10 to 75% by weight of active ingredient,
1~2~4t7~
from 0.5 to 15% by weight of surface-active agent, from
0~1 to l~o by weight of thixotropic agents, from 0 to 10%
of suitable additives, such as anti-foam agents, corrosion
inhibitors, stabilisers, penetrating agents and adhesives,
and, as the carrier, water or an organic liquid in which
the active ingredient is substantially insoluble; certain
organic solids, or inorganic salts, can be dissolved in
the carrier in order to assist in preventing sedimentation
or to act as anti-freeze agents for water.
Aqueous dispersions and aqueous emulsions, which
are obtained by diluting the abovementioned compositions
with water, in particular the wettable powders and
emulsiEiable concentrates according to the invention, are
also included in the general scope of the present invention~
The emulsions thus obtained can be of the water-in-oil type
or of the oil-in-water type and they can have a thick
consistency such as that of a mayonnaise.
All these aqueous dispersions and emulsions, or
spraying mixtures, can be applied by any suitable means to
the crops in which weeds are to be destroyed, mainly by
spraying, at doses which are generally of the order of
500 to 1,000 litres of spraying mixture per hectare.
As indicated above, the invention also relates
to a method for the control of insects in crops, which
comprises applying an effective amount or at least one of
the compounds of ~eneral iCormula I to the aerial part of
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the crops and/or to the soil or incorporating the
compound into the soil~
For the control of insects, the compounds of
general Eormula I are used at concentrations of from 0~01%
to about 1% by weight of the total formulation~ As
nematocides, the active component is effective within the
range of about 0.5 to 5 kg/hectare~ Under ideal conditions,
depending on the pest to be controlled, the lower rate may
offer adequate protection. On the other hand, adverse
weather conditions, resistance of the pest and other factors
may re~uire that the active ingredient be used in higher
proportions.
When the pest is soil-borne, the formu~ation
containing the active ingredient is distributed evenly over
the area to be treated in any convenient manner. The active
component can be washed into the soil by spraying with
water over the area or can be left to the natural action
of rainfall. After application, the formulation can be
distributed in the soil by ploughing or disking.
Application can be prior to planting or after planting
but before sprouting has taken place or after sproutiny.
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SUPPLEMENTARY DISCLOSURE
,
EXAMPLE 21
Dry triethylamine (dried over a 4A molecular
sieve 1.52g; 2.1ml; 0.015mol) was added at laboratory
temperature to a solution of 2-fluorophenol (1.68g;
0.015mol) in acetone (Pronalysis grade, 30ml). The
solution was then stirred magnetically at laboratory
temperature while S-tert-butyl ethylphosphonothioic
chloride (2.0g; 0~01mol) was added dropwise over 4
minutes, during which time the temperature rose to
33C and a solid began to separate. Stirring was
continued at ambient temperature for 17 hours. The
reaction mixture was then poured into water (50ml) and
extracted with diethyl ether (2 x 25ml). The combined
ethereal extracts were washed with 2N aqueous sodium
hydroxide solution (2 x 25ml) and water (2 x 25ml),
dried over anhydrous sodium sulphate, filtered and
evaporated to give 0-(2-fluorophenyl)-S-tert-butyl
ethylphosphonothioate in the form of a brown oil
(2.2g, 71.4% yield). The product was 98% pure and was
identified by its phosphorus and proton magnetic
resonance spectrum.
By proceeding in a similar manner but
replacing the 2-fluorophenol by 3-fluorophenol and
4-fluorophenol, there were prepared, respectively, the
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followin~ products which were identified by their
phosphorus and proton magnetic resonance spectra:-
0-(3-fluorophenyl)-S-t_ -butyl ethyl-
phosphonothioate (purity 98%);
0-(4-fluorophenyl)-S-tert-butyl ethy~hosphono-
thioate tpurity 99/O)~
~ ,
