Note: Descriptions are shown in the official language in which they were submitted.
The present invention relates to the use of 3,5-di-t-butyl-4-
hydroxydiphenylmethane as an insecticide. In particular, this compound
exhibits good insecticidal activity against larvae of mosquitoes.
In recent years, the use of agricultural chemicals has caused no
small amount of public nuisance and pollution of the environment such that
serious social problems have been raised. Accordingly, it has particularly
been desired to develop an insecticide which is able to selectively extermin-
ate insect pests, but which has no harmful effect on other organisms.
As the result of extensive study it has been found that compounds
represented by the following general formula I
R
2 ~ ~ OH (I)
~'~=< .
( 3)3
wherein R is hydrogen or t-butyl, with the proviso that the hydroxyl group
is located in the ortho position with respect to R and at least one t-butyl
group is present in the ortho position with respect to the hydroxyl group,
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exhibit excellent insecticidal activity against larvae of mosquitoes and
are therefore useful as insecti~ides9 Furthermore, these compounds are
also useful in combatting larvae of mosquitoes which have become resistant
; to organic chlorine or phosphorus containing insecticides. Some of the com-
pounds within the above formula I are novel and are the su~jec~ of our
Canadian Patent Application Serial No. 200,756, filed May 2~, 1974 from
which this~application is divided.
According to one aspect of the invention, therefore, there is ~ -
provided an insecticidal composition which comprises an insecticidally
, . .
s effective amount of 3,5-di t-butyl-4~hydroxydiphenylmethane and an inert -
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carrier or diluent.
According to a further aspect of the invention there is provided
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a method for exterminating larvae of mosquitoes which comprises applying to
said larvae an insecticidally effective amount of the compound 3,5-di-t-
butyl-4-hydroxydiphenylmethane.
Examples of insecticidally active compounds are illustrated in
the following table. In the Examples and table, Compound I is the compound
whose use as an insecticide is the subject of this application. Compounds
II and III are in acco danoe with our Application Seridl No, 200,756.
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Illustrative syntheses of the compounds are as follows:
Synthesis 1
A 100 ml autoclave was charged with 18.4 g of p-ben7ylphenol and
1 g of aluminum isopropoxide and the reaction carried out at 120C. to
obtain aluminum benzylpheno~ide~ To this product was added 11.2 g of liquid
isobutylene and the reaction mixture was raised to a temperature of 136C.
with stirring and allowed to react for about 8 hours. Then the reaction
mixture was extracted with ether to give mixtures of compounds I and II of
Table 1. From the mixture, each of compounds I and II was isolated by a
column chromatography (silica gel/cyclohexane).
-,
; Synthesis 2
10.3 g of 2,4-di-t-butylphenol was dissolved in an appropriate
amount of toluene. Then 2 g of sodium hydroxide dissolved in a small amount
of water was added and the reaction was carried out under dehydration by an
azeotrope of toluene and water at 105-110C. to give the sodium salt. Before
I the dehydration was complete and while the toluene still remained, 1206 g
i of benzylchloride was added dropwise at 100C. with stirring to continue
, the reaction for 2 hours. The reaction mixture was then distilled under
`1 reduced pressure to give a fraction of 127 to 13?C /2 to 3 mmHg, which
; 20 fraction was further purified by a column chromatography to obtain compound
i III.
The compound 3,5-di-t-butyl-4-hydroxydiphenylmethane can be used
li in association with ~mixed with) an inert carrier or diluent, and preferably
y in association with a homogeneously dispersed in, one or more compatible
.. . .
insecticidally-acceptable carrier substances in accordance with any manner
usually employed in formulating agricultural and insecticidal chemicals. The
term "compatible insecticidally-acceptable carrier substance" as used herein
has a broad definition and signifies carrier substances of the type generally
accepted in the art as being suitable for use in insecticidal compositions
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and which are compatible with the acti-ve ingredient compound of general
formula I. The term thus includes both liquids and solids, e.g., carriers,
diluents, solvents, adjuvants such as spreaders, emulsifiers, suspending
agents, stabilizers, synergists or the like, and other insecticides, bacteri-
cides and herbicides7 etc. The insecticidal compositions in accordance
with the present invention thus include solutions, emulsions, suspensions,
dispersible (wettable) powders, emulsifiable concentrates, granular formula-
tions including microcapsules, and dusts. All of these compositions comprise
the compound in dispersed or readily dispersible form and a carrier substance,
with or without adjuvants. In general, selective extermination of mosquito
larvae is obtained by applying an effective amount of the compound to said
larvae.
The insecticidal efficacy of the compound is of high order and it ~-
can be applied at relatively low rates for controlling survival, pupation
and/or emergence of mosquito larvae. Illustratively, the compound gives
complete or substantially complete suppression of mosquito larvae at rates -
of about 0.01 to 10 ppm (parts per million) in water. Little or no adverse ~ -
effect is apparent to other insects, mammals, aquatic animals or plants~at - -
these and even somewhat higher rates of application. It will be understood
that a choice of concentration of active ingredient depends upon the method
of application as well as the type of composi~ion. The concentration of ;
ac~ive ingredient in the dispersible powder and the emulsifiable concentrate
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formulations from which aqueous compositions can be prepared may be as high
as 99.5% by weight. The concentration of active ingredient in the granular
and dust formulations of the present invention can vary from about 0~25% to
.. .. .
about 80% by weight or more, but advantageously is of the order of 0.5% to
20%o
The granular carrier substance may be, for example, vermiculite,
pyrophyllite or attapulgite. The active ingredient may be dissolved in a
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volatile solvent such as acetone, methanol, ben7ene, and the like, and
sprayed on the granular carrier substance as it is mixed and tumbled and
the granules are then dried. The granular carrier substance can range in
particle size from about 10 to about 60 mesh, preferably about 30 to about
60 mesh.
The insecticidal dust compositions are prepared with a solid
pulverulent carrier substance which maintains the compositions in a dry,
` free~f]owing state. The active ingredient may be ground with ~he carrier
substance or the active ingredient may be dissolved in a vo:Lati]e organic
`~ 10 solvent of the kinds indicated above and then sprayed on the carrier sub- -
stance so as to assure thorough distribution. The mixture is then dried
and milled to the desired size, e.g~, less than about 60 microns. Solid
carrier substances that can be used in the dust compositions of the present
invention include the natural clays such as China clay and bentonite,
minerals in the natural state such as talc, pyrophyllite, quartz, diatomaceous
earth, fuller's earth, chaIk and rock phosphate, and the chemically modified
i minerals such as washed bentonite, precipitated calcium phosphate, carbonate
or silicate and colloidal silica.
The dust compositions of the present invention can be rendered
dispersible by incorporating a surfactant therein. The resulting dispersible
; powder can be dispersed in water to any desired concentration. Conveniently,
the dispersible powders are formulated with higher concentration of active
.ingredient than the dust compositions ~ , for example, up to 90% by
weightj preferably about 10% to about 80%o Surfactants useful in preparing
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~ the powdered compositions may be either non-ionic, anionic, or cationic in
-~ nature. Suitable non-ionic surfactants include glycerol monostearate,
sorbitan monolaurate, sorbitan monopalmitate, polyethylene glycol, polyoxy~
~- ethylene laurylether, polyoxyethylene octylphenylether, polyoxyethylene
^ nonylphenylether, and polyoxyethylene isooctylphenylether. Suitable anionic ~
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surfac~ants include potassium laurate, natrium oc-tylsulphate, natrium
laurylsulphate, natrium tetradecyl sulphate, natrium octylsulphonate, natrium
n-octylbenzene sulphonate, natrium n-hexadecylbenzene sulphonate and natrium
tetrapropylenebenzene sulphonate. Suitable cationic surfactants include n-
octylamine hydrochloride, n-dodecyl trimethylammonium bromide, dioctyl-
- dimethyl ammonium chloride, and n-dodecyl oyridinium chloride.
The compound can also be used without a solid carrier substance.
; Preferably it is ground with and/or dissolved in a suitable organic solvent
which preferably is immiscible in water so that an emulsion of the solvent
; 10 in water ean be prepared. One or more carrier solvent substances with or
without a co-solvent can be used in order to obtain concentrated solutions
of the active ingredient~ ;
The emulsifiable concentrates of the present invention can be
prepared by grinding the active ingredient and a surfactant with a substan- -~
tially water-immiscible solvent carrier substance or by dissolving the active
ingredient and surfactant in the solvent. Suitable solvents include
aromatic hydrocarbons such as benzene, xylene, toluene~ solvent naphtha,
naphtalene, and kerosine. If desired, a co-solvent such as methanol,
ethanol, isopropanol, isophorone, or tetrahydrofuran ean be included with
the solvent earrier substance in order to enhance solubility of the active
ingredient. Aqueous emulsions are then prepared by mixing with water to
give any desired coneentration of the active ingredient. Surfactants which
; can be employed in the emulsifiable concentrates are those types disclosed
above~ Mixtures of surfactants can be employed if desired. Advantageously,
l the eoncentration of active ingredient in the emulsifiable concentrates can
i range from about 5% to about 50% by weight, preferably from about 10% to
about 50% by weight. ~-
The following example is illustrative of the insecticidal com-
positionsof the present invention.
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Example 1
50 parts of compound I, 40 parts of benzene and 10 parts of
polyoxyethylenenonylphenylether were mixed together and ground to give 100
parts of an emulsifiable concentrate.
The insecticidal effectiveness of -the compositions of the present
invention are illustrated in the following examples:
A. 180 ml of stored water was placed in a glass pot having a
diameter of 9 cm and a height of 9 cm. An emulsifiable concentrate of test
compound I (active ingredient) prepared according to the procedure of
Example 1 was diluted with water and 20 ml of the resultant emulsion added
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to the glass pot to give a total volume of 200 ml. The amount of emulsifi-
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able concentrate used was c~lculated to result in a concentration of 100 ppm
in the water. 10 larvae of four~h instar of ~ ,D~Ll3~ were
released into the pot maintained at a constant temperature of 25C. and fed
with an appropriate amount of Ebios (registered Trade Mark) which is a
powdered yeastO The numbers of surviving larvae, pupae and emerged adults
i . ~ .
were observed daily after release of the larvae into the pots and the results
are shown in the following Table 2.
B. The procedure of paragraph A was repeated three times with the
exception that the amounts of emulsifiable concentrate used were calculated
to result in concentrations of 10 ppm, 1 ppm and 0.1 ppm, respectively, in
~i the water. The results are also shown in the following Table 2.
. ........................................................................ .
. The procedures of paragraphs A and B above were repeated for ~ ;
Test Compounds II and III and the results are shown in Table 2~ ~-
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In Table 2, the % survival of larvae, ~ mortality of lar-vae,
% pupation and % emergence all are based on the number of larvae released
into the pot, the number of larvae which died just after pupation being
included in the n~ber of dead larvae. The rearing water was kept at a
constant volume of 200 ml over the entire test period. The values in the
table represent the average of two identical tests.
As can be seen from the test results in Table 2, the insec~icides
are, unlike ordinary insecticides, very similar in insecticidal activity to
juvenile hormones. This îs apparent, for e~ample, from the fact that
pupation of the larvae was retarded, that the larvae died just after pupation
or that the dead pupae did not brown like normal pupae.
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; A. To a 1/2000 are ~pot. (water depth 20 cm) in which 2000 to 3000
; of first to fourth instars of larvae of Culex pipiens pallens were living,
was added 5 ml of an emulsifiable concentrate of the test compound I pre~ared
in accordance with the procedure of E~ample 1, and the pot was allowed to
stand outdoors during the summer months. Subsequently thereto, the number
of surviving larvae pupae and emerged adults were observed. The results one
month after treatment are shown in the following Table 3.
~. The procedure of paragraph A above was repeated with the
exception that 0.5 ml of the emulsifiable concentrate was added to the pot.
The results are also shown in the following Table 3.
C. The procedures of paragraphs A and B above were repeated
` with ~he e~ception that an emulsifiable concentrate of a control test compo~md7
which was 27~-di-tert-butyl-4-cumylphenol, was used. The results are shown
~ in Table 3.
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Quantity of One month after treatment
Test Compound emulsion of _ _ _
test compound % Survival % pupation % emergence
(ml)of larvae
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Compound I 5 O O O
0.5 O O O
` Control 5 O O O
0.5 0 65 60
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Blank tes~ o 100 100
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In Table 3, the % survival of larvae, % pupation and % emergence
are all based on the mlmber of larvae released into the pot. Over the
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entire test period, the rearing water in the pot was kept at a constant level
while partly being refreshed at the rate of 100 ml/hr. -
As is apparent from the results in Table 3, the active ingredient
., .
of the insecticide in accordance with the present invention exhibits superior
insecticidal activity compared to the control compound. Furthermore, the
active ingredient exerts specific insecticidal action only on the larvae of
,ll 10 mosquitoes, and has very low toxicity and little harmful effect on other
insects, mammals, aquatic animals and plants. For example, Compound I ~--
exhibited no toxic effect on killifish (Or2~zias latipas) exposed for 72 hours
to 100 ppm concentration thereof or on mice given 300 mg/kg orally. ~ -
With respect to microbiological degradability (biodegradability), - ~ ~
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` consis-tent with the generally accepted fact that the degradability of an
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aromatic compound is enhanced by the presence of a hydroxy or carboxy group,
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good degradability. In addition, the compound consists only of carbon, ;
hydrogen and oxygen, so that its decomposition products cause little environ-
.
mental pollution
As described in the foregoing, 3~5-di-t-butyl-4-hydroxydiphenyl-
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methane, besides being effective insecticides against the larval form of
mosquitoes, fulfill substantially all the requirements for the prevention
of chemical hazards to plants and other animals and for control of environ- :
mental pollution.
The insecticidal compositions of the present invention can be
applied to the mosquito larvae in any conventional manner.
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