Note: Descriptions are shown in the official language in which they were submitted.
1 157771
Insecticidal compositions
This invention relates to new insecticidal
compositions containing certain novel compounds.
Throughout this specification, where the context
permits, the word "insect" is used in its broad common
S usage and includes spiders, mites, nematodes and other
pests which are not classed as insects in the strict
biological sense. Thus the term implies reference not
only to those small invertebrate animals belonging mostly
to the class Insecta, comprising six-legged, usually
winged forms, such as beetles, bugs, flies and the like,
but also to other allied classes of arthropods whose
members are wingless and usually have more than six legs,
such as spiders, wood lice and the like, and expecially
to the order Acaridae which includes the mites and ticks.
The words n insecticide" and n insecticidal" are similarly
used.
According to the invention there is provided
insecticidal compositions comprising one or more of
the compounds of formula I
R2
~ CooR3 Y
Rl ~ 1 C y2
l l I
y6_ C- C - Y3
S 4
Y Y
1 157771
-- 2 --
wherein Rl is hydrogen or a methoxy, ethoxy, propoxy,
butoxy, tetrafluoroethoxy, methylthio, ethylthio, propyl-
thio, fluoro, chloro, bromo, methyl, ethyl, or nitro
group, and R2 is hydrogen or a methyl group, or Rl and
R2 together form a methylenedioxy group;
R3 is one of the following groups (a) to (f):-
(a) ~
CH2 ~
0~
(b)
O
( C ) .
CN
(d)
~ ~CH2
CH2 ~
~e)
C--C~O ~
1 157771
- CH ~~~ O ~
I ~ \ ~ Cl
and yl y2 y3 y4 Y5 and y6 are the same or
different groups and each is hydrogen or a fluoro,
bromo or chloro group, with the proviso that when Rl is
hydrogen, fluoro, chloro, bromo or methyl and R2 is
hydrogen or methyl, then at least one of yl to y6 is
other than hydrogen; said compound(s) being incorpor-
ated in a suitable inert liquid or solid carrier, and
additionally containing at least one synergistic or
potentiating agent of the class of microsomal oxidase
inhibitors.
Our related application 318,086 filed on December 18,
1978, of which the present application is a division,
claims the compounds of formula I (and the related free
acid and lower alkyl esters) by themselves i.e. in the
absence of any synergistic agent, as these compounds are
novel.
Known compounds which can be regarded as related to
the said novel compounds are those in which the groups (a)
to (f) are present as esterifying groups with chrysanthe-
mic acid in commercial or experimental pyrethroids. Our
Australian Patent No. 502,950 describes and claims a
similar class of esters.
West German Patent Specification D~-OS 27 33 740
descri~es compounds of the formula I in which all of the
groups yl to y6 are hydrogen, Rl and R2 are each
hydrogen, or a fluoro, chloro, bromo or methyl group and
R3 is one of the groups (a), (c) and (e) above. Such
compounds are excluded from the present invention.
In the compositions of this invention it is prefer-
able to employ compounds of formula I in which Rl is a
~ 1~7771
-- 4 --
methoxy, ethoxy or propoxy group and R2 is hydrogen.
Compounds in which Rl and R2 form the methylenedioxy
group are also preferred.
Preferably also, R3 is one of groups (a), (c) and
(e) as defined above.
It is also preferred that from one to all six of the
groups yl to y6 is a fluoro group, the remainder (if
any) being hydrogen. Tetrafluoro-substitution (yl, y2
Y3, Y4 = F; y5, y6 = H) is especially preferred.
Specifically preferred compounds for use in the
compositions of the invention are as follows:-
3'-phenoxybenzyl 1-(3,4-methylenedioxyphenyl)-
2,2,3,3-tetrafluorocyclobutanecarboxylate, and its 'a-cyano
and -ethynyl derivatives; 3'-phenoxybenzyl 1-(4-ethoxy-
phenyl)-2,2,3,3-tetrafluorocyclobutane carboxylate, and
its a-CyanO and ~-ethynyl derivatives.
The compounds of formula I are in themselves
extremely active insecticides, having an insecticidal
activity an order of magnitude greater than most known
insecticides. These compounds also possess the property
of contact repellency to insects, and are generally more
active against flies than the compounds of our afore-
mentioned Australian patent.
However, the compounds of formula (I) are unex-
pectedly further improved in insecticidal activity whencombined with certain other substances found to have a
synergistic or potentiating action. Such substances are
of the class of microsomal oxidase inhibitors i.e., they
inhibit the detoxification of insecticides in insects
produced by the action of oxidative enzymes. Typical
substances of this type are the pyrethrin synergists of
which the following are examples:-
- 5 _ ) 157771
Common Name Chemical Name
Piperonyl butoxide ~[2-(2-butoxyethoxy)etllo~y]-
4,5-methylenedioxy-2-propyl-
toluene
Piperonyl cyclonene 3-he~yl-5(3,4-methylenedioxy-
phenyl)-2-cyclohexanone
"Se~oxane" (Sesame~) 2-(3,4-methylenedioxy-phenoxy)-
3,fi,9-trioxaundecane
"S~lfoxide" 1,2-(methylenedioxy)-4-[2-
ln (octylsulfinyl)propyll-benzene
n-Propyl isome dipropyl-5,6,7,8-tetrahydro-
7-methylnaphtho-~2,3-dl-1,
3-dioxole-5,6-dicarboxylate
("Sesoxane", "Sesam~x~ and "Sulphoxide" are Registered
Trade Marks).
We have found that 'Sesoxane' (made by Shulton
Inc., Clifton, N.J., U.S.A.) is particularly useful as a
potentiator. The amount of 'Seso~ane' used may vary
from l/lOOOth to five times the wei~ht of the compound
I,the preferred range being ~rom about l/lOOth to an
equal part by ~-eight. Piperonyl butoxide also is a
useful potentiator in similar amounts.
The compounds of formula I are optically active and
can be resolved into their optical isomers by conventional
methods. ~ither the individual (+) and (-) optical isomers
of the compounds or the racemic (+) forms can be employed,
although it should also be noted that the insecticidal
activities of the optical isomers of the compounds I may
differ by an order of magnitude or more.
The compounds I may be prepared by esterification of the
free acid (formula I, R3 = H) with the appropriate alcohol
R30H, where R3 is one of the groups (a) to (f). Such
esterification may be carried out by any suitable known method,
e.g., by direct reaction or by prior conversion of the acid
and/or the alcohol to a suitable reactive derivative, or by an
ester interchange reaction between the alcohol R30H (R3 =
(a) to (f)) and a lower alkyl ester of the acid.
The acid (formula I, R3 = H) is prepared by the
reaction of an appropriately substituted benzyl compound
40 with an appropriately substituted 1,3-dihalopropane to
form a l-phenylcyclobutane compo~nd which can be
l 1S7771
-- 6 --
hydrolysed to the acid. This reaction scheme is as
follows: R2
>~
Ph = Rl ~
yl y3 yS z yl
Ph-CH2Z + X- C - C - C X ~ Ph - C - C y2
y2 y4 y6 y6 _ C - C - y3
~/~ydro/lysis
COOH yl
Ph - C - C y2
y6 _ 1 - C y3
y5 y4
where Z represents a group which activates the benzylic
methylene and is itself later hydrolysable to a carboxyl
group, e.g., -C-N or -COOEt; X represents a chloro, bromo
i d p Rl R2 yl y2, y3~ y4, yS and y6 are as
defined above.
An alternative method of preparation of the acid
(formula I, R3 = H) as its lower alkyl ester is by
addition of the olerin YlY2C CY Y to the substituted
phenylacrylic ester of formula II
R\
~\
Rl ~ C COOR II
y6 \y5
~ 157771
where R is a lower alkyl group and R , R , yl~ y , y ,
y4, Y5 and y6 are as defined above.
Esters of formula I (R = lower alkyl) wherein
3 y4 F and yl = y2 = yS = y~ = H can be made by
first preparing the compounds wherein Y3 = Y4 = F, yl = y
= Cl according to the preceding method (using dichloro-
difluoroethylene) and then hydrogenating the product to
replace the chlorine groups by hydrogen. -
The esters II wherein y5 = y6 = H may be obtained
according to the following general procedure:(1) A lower alkyl ester of the appropriately substituted
phenylacetic acid (V) is condensed with a di(lower alkyl)
oxalate in the presence of a basic catalyst, to produce
an enolate salt (IV).
(2) The solution of the enolate salt is acidified to
give the corresponding phenyloxaloacetate (III).
(3) The compound III is reacted with formaldehyde under
alkaline conditions to give the phenyl hydroxymethyl
acetate which on dehydration (sometimes spontaneously)
yields the phenylacrylic ester (II).
This reaction sequence is illustrated in the
following overall reaction scheme. It will be
appreciated that the specific acids and bases indicated
may be replaced by other suitable compounds. Also lower
alkyl esters, other than the ethyl esters shown may be
employed.
1 157771
Ph-Cl~2-CEt EtO-CO-CO-OEt Ph-CH-COOEt
NaOET
~ OET
C (IV)
¦ ONa
COOEt
CH3COOH /
Ph-CH-COOEt Ph-CH-COOEt
CO HCHO/K2C03 l H2
COOEt OH
(III)
~~
5 Ph-C-COOEt
CH2 (II R=Et, y5 = y6 = H)
When y5 = y6 = F, the esters II can be made
according to the method described by D.G. Naae and D.J.
Burton, Synthetic Communications, 3, 197-200 (1973) .
In this method the appropriate phenvl keto ester of
formula VI is reacted with dibromodifluoromethane
(CBr2F2) in the presence of 2 moles of tris
(dimethylamino)phosphine and a suitable solvent such as
diglyme or triglyme
I ~S7771
Ph - C - COOR + CF2Br2 ~ Ph - C - COOR
Il 11
O CF2
VI II (yS = y6 = F
where Ph is as defined above and R is a lower alkyl
group.
The general approach to formation of the esters
S of the invention is as follows:-
* A - COOEt ~ j A - COOH
A - Coo~{ ~ A - COCl
A -- COCl + R OH > A - CoOR3
where A is
R yl
Rl ~ y2
y6 1 I y3
y5 y4
Rl R2 R3 yl y2 y3 y4 Y5 and
y6 are as defined above.
Alternatively the ethyl ester can be directly
converted as follows:-
A - COOEt + R30H ~ A - CoOR3 + EtOH
The compositions described herein may be in liquid
or solid form. Useful liquid compositions, which may be
incorporated, for example, into aerosol-type dispersions
with the usual propellants, may be made by dissolving
the insecticidal compound(s) of Formula I and the chosen
synergist in a suitable organic solvent, or mixture of
solvents, to form solutions or by dispersing such organic
solvent solutions in water to form aqueous suspensions.
Useful solid compositions may include inert solid
diluents or carriers in addition to the active in-
gredients. Such compositions may also include other
,,
1 157771
-- 10 --
substances such as wetting, dispersing or sticking agents,
and may be prepared in granular or other forms to provide
slow release of the compounds over an extended period of
time. The compositions may contain other insecticides
such as pyrethrum, rotenone, or with fungicidal or bacter-
icidal agents, to provide compositions useful for household
and agricultural dusts and sprays, textile coating and
impregnation, and the like.
The preparation and properties of the compositions
Of the invention are illustrated by the following specific
examples. It should be noted, of course, that these
Examples are intended to be illustrative of the methods
and procedures utilized in preparing the compositions and
the constituents employed therein and that they are not
intended to be restrictive of the invention.
Examples 1 to 20 illustrate the preparation of the
compounds of formula I and related compounds, and Examples
21 and 22 show the effects of the compositions of this
invention compared to the compounds of formula I above.
EX~lPLE 1 (Prior Art Compound)
(a) l~ chlorophenyl)cyclobutane nitrile
4-Chloroben~yl cyanide (10 g) in dry DMS0 (20 ml) was
added over 5 min to a stirred suspension of sodium
hydrid~ (4.4 g) in DI~lSO at 25C under argon. The
mixture was stirred for 30 minu~es then a solution of
1,3-dibromopropane (27 q) in dry DMSO (50 ml) was added
over 30 minutes while maintaining the tem~erature of the
reaction mixture at 25-30C. After stirring an
additional ~0 minutes at this temperature the reaction
3~ mixture was added to ice water (500 ml) and extracted
~ith dic;~lorolrethane ~3 x 75 ml). The e.;tracts were
evaporated and the residue extracted with diethyl ether
~4 x 50 ml). The ether extracts were washed with water,
dri~d over anhydrous sodium sulphate and evaporated to
yield an oil (lO.8 g) which on distillation gave the
nitrile lbP 90/10 Torr.] yield 5.4 g (43~
- 1 157771
Analysis: C 68.48~ H 5.49~ Cl 18.3%. CllHloCl N
requires: C 68.93~ H 5.26~ Cl 18.5%.
(b) 1-(4-chlorophenyl)cyclobutane carboxylic acid
1-(4-chlorophenyl)cyclobutane nitrile (5 g) was mixed
with ethylene glycol (60 ml~ and 40% w/w aqueous potassium
hydroxide solution (80 ml) and refluxed under argon for
18 hours. The mixture was cooled, added to ice water and
extracted with diethyl ether. The aqueous layer was
acidified and the precipitate was filtered off, washed
with water, dried and recrystallised from petroleum
ether (b.p. 40 - 60) to give the acid as white needles
mp 88 - 9 , yield 4.5 g (82%). Analysis:
C 62.70~ H 5.14% Cl 16.5% O 15.2~. CllH11C1O2 requires:
C 62.72% H 5.26~ Cl 16.83% o 15.2%.
(c) 3'-phenoxybenzyl 1-(4-chlorophenyl)cyclobutane-
carboxylate
1-(4-Chlorophenyl)cyclobutane carboxylic acid (1 g) was
dissolved in thionyl chloride (1 ml) and heated at reflux
for 40 minutes. Excess thionyl chloride was removed in
vacuo and the residue was taken up in petroleum eth~r
40 - 60 (40 ml) and added over 15 minutes to a stirred
mixture of 3-phenoxybenzyl alcohol (1.1 g), pyridine
(1 ml), benzene (50 ml) and petroleum ether 40 - 60
(50 ml) maintained at 10C. The mixture was stirred at
20 - 25C for 3 hours then added to ice water, washed
with 0.5M hydrochloric acid, water, dilut2 sodium
bicarbonate solution and dried over anhydrous sodium
sulphate. The solvent was evaporated to give an oil
(2.3 g) which a~ter chromatography on silica gel, eluting
with benzene/petroleum ether, gave the ester 1.52 g (82~).
Analysis: C 72.87% H 5.30% Cl 9.2% o 12.1~
C24H21 C103 requires: C 73.37% H 5.39% Cl 9.0% O 12.2%.
1 157771
- 12 -
EX~MPLE 2
(a) 1-(4-ethoYyphenyl-)cyclobutane -carboxylic acid
Ethyl 4-ethoxyphenylacetate (14 g) in anhydrous diethyl
ether (20 ml) was added to a stirred suspension of
sodamide (5.3 g) in liquid ammonia (400 ml) over 3
minutes and the mixture stirred for an additional 20
minutes. 1,3-dibromopropane (14 g) in diethyl ether
(10 ml) was added over 20 minutes and the mixture
stirred for 17 hours. 50 ml of saturated ammonium
chloride solution was added and the reaction mixture
extracted with diethyl ether. Evaporation of the solvent
gave a residue (17.4 g) which after chromatography on
silica gel by eluting with benzene/chloroform gave an
oil (7.2 g). The oil was dissolved in ethanol (50 ml)
and 10% sodium hydroxide solution (50 ml) was added.
The mixture was refluxed for 3 hours, cooled, added to
ice water and extracted with diethyl ether. The aqueous
layer was acidified and the precipitate was filtered off,
washed with water, dried and recrystallised from petroleum
ether 40 - 60 to give the acid 5.2g (35%) mp 90-1C.
- Analysis: C 71.04~, H 7.23% O 22.0~ C13H16O3 requires
C 70.89% H 7.32~ o 21.8%.
(b) 3'-phenoxybenzyl 1-(4~ethoxyphenyl)cyclobutane
carboxylate
1-(4-ethoxyphenyl)cyclobutane carboxylic acid (1 g) was
refluxed in thionyl chloride (1 ml) for 30 minutes and
the excess thlonyl chloride removed in vacuo. Th~
residue was taken up in petroleum ether 40-60 (25 ml)
and added over 5 minutes to a stirred mixture of
3-phenoxybenzyl alcohol (l.lg) pyridine (1 ml) benzene
(25 ml) and petroleum ether 40-60~ (25 ml) at 15C. The
mixture was stirred at 15C for 3 hours, then added to
ice water and extracted with diethyl ether. The extract
-
1 157771
- 13 -
was washed with water, 0.5M hydrochloric acid, and sodium
bicarbonate solution then dried over anhydrous sodium
sulphate and the solvent removed to give an oil (2.1 g).
Chromatography on silica gel, eluting with benzene, gave
S the ester 1.5g (82%).
Analysis: C 77.55% H 6.65~ O 16.0% C26H26O4 requires
- C 77.59% H 6.51% O 15.9%.
EXAMPLE 3
(a) 2-(4-ethoxyphenyl)propenoic acid ethyl ester.
-
This part of the example shows the general method
of forming the 2-aryl-acrylic acid esters. (Formula II)
Alcohol-free sodium ethoxide freshly prepared
from sodium (13.9g) and excess ethanol was slurried in
dry ben~ene (200 ml). To this suspension diethyl
oxalate (88.5g) was added over 15 minutes. Ethyl-p-
ethoxyphen~lacetate (V) (114.2g) was added to the
resulting clear yellow solution over 30 minutes at roo~
temperature. After a further 1 hour period the reaction
mixture solidified. The solid, sodium diethyl-2-p-
ethoxyphenyl-3-ethoxy-3-oxido-oxaloacetate (IV) was
triturated and washed well with ether. The combined
ether washings were evaporated to a small volume to obtain
a second crop of the salt.
The combined yield was 227.4g.
The sodium salt was acidified by adding it in
portions to a well stirred emulsion of equal parts of
diethyl ether and dilute acetic acid (approximately 10%).
~fter separation the ether layer wi~s washed with water and
dilute sodium bicarbonate solution, and dried with
anhydrous sodiwn sulphate. After evaporation of the
ether, the resulting oil was crystallized from petroleum
ether (b.p. 60 - 80), to yield diethyl-2-p-ethoxyphenyl-
oxaloacetate (III) 143.8g (85~), m.p. 59 - 60 .
The keto-ester III (1~3.8g) was stirred in dilute
formaldehyde solution (62 ml 37~ formald~hyde + water
~ 157771
- 14 -
220 ml) and to the suspension potassium carbonate
solution (54.5g, in water 280 ml~ was added aropwise. At
the end of the addition, ether was added to the stirred
suspension to dissolve the gummy precipitate which formed
and after an additional lS minutes, gas evolution
commenced. When this gas evolution ceased (after about
2 hours) the reaction mixture was extracted with
additional ether and the combined ether extracts were
washed with water and evaporated after drying with
Na2SO4. The yield of the ethyl 2-(4-ethoxyphenyl)
propenoate (ii~ (isolated as a yellow oil) was 97.8g
(79.8~).
~b) ~Ethyl 1-(4-ethoxyphenyl)-2,-2,3,3-tetrafluorocyclo-
butane carboxylate
2-(4-ethoxyphenyl)propenoic acid ethyl ester (13.2 g)
was mixed with benzene (7.5 ml), a-pinene (2 drops)
N-ethyldiisopropyl amine (2 drops) and tetrafluoroethylene
(15.5 ml) and heated to 150-155 for 24 hours then
155-60C for 17 hours. After evaporation of volatile
materials the residue (16.6 g) was dissolved in dichloro-
methane and chromatographed on a column of silica gel to
give the ester as a colourless oil 14.5g (75~). Analysis:
C 56.47%, H 5.24%, F 23.4~. ClSH16F4O3 requires
C 56.25%, H 5.04~, F. 23.7%.
(c) 1-(4-ethoxypheny~-2,2,3,3-tetrafluorocyclobutane
carboxvlic acid
Ethyl 1-(4-ethoxyphenyl)-2,2,3,3-tetra~luorocyclobutane
carboxylate (14.5 ~) was dissolved in ethanol (100 ml)
and a 10% w/w solution of sodium hydroxide in water
(100 ml) was added and the mixture refluxed for 2.5
hours. The mixture was cooled, added to ice water and
extracted with diethyl ether. The aqueous layer was
l 157771
- 15 -
acidified and the precipitate was filtered off, washed
with water, dried and crystallised from 6Q - 80
petroleum ether to give the aci~d mp 112-3C. Yield
11.2g (85~!. Analysis: C 53.20~ H 4.22%, F 25.9%.
C13H12F4O3 requires C 53.43~ H 4.14% F 26.0%.
(d) 3'phenoxybenzyl 1-(4-ethoxyphenyl)-2,2,3,3-tetra-
fluorocyclobutane-carboxylate
1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclo~utane
carboxylic acid (0.9 g~ was refluxed with thionyl
chloride (1 ml) for 45 minutes and the excess thionyl
chloride was removed in vacuo. The residue was dissolved
in petroleum ether 40-60 (40 ml) and added over 5
minutes to a mixture of 3-phenoxybenzyl alcohol (1 g),
pyridine (1 ml~, benzene (25 ml), and petroleum ether
40 - 60 (25 ml) maintained at 20C. The mixture was
stirred for 3 hours then added to ice water and extracted
with diethyl ether. The extract was washed with water,
O.SM hydrochloric acid, and sodium bicarbonate solution,
dried over anhydrous sodium sulphate and the solvent
evaporated to give an oil t2 g). Chromatography on
silica gel by eluting with benzene gave the ester 1.2 g
(82%). Analysis: C 65.45%, H 4.84~ F 16.0%. C26H22F44
requires C 65.82%, H 4.67~, F 16.0%.
EX~PLE 4
(a) (-) Enantiomer of 1-(4-ethoxyphenyl)-2,2,3,3-
tetrafluorocyclob~a'ana carboxylic acid
~+~-(l-naphthyl)ethylamine was added to a solution of
the racemic acid (2g) (prepared as in Example 3(C)) in
ethyl acetate (75 ml~ and n-hexane. The salt which formed
was crystallized four times ~rom ethyl acetate at room
- temperature. The (+)(-) salt was decomposed with
hydrochloric aci~d (lM) and the residue recrystallized
1 157771
- 16 -
twice from ethanol. The (-) acid which had ~20 =-118.2
and m.p. 194C was obtained in 15~ yield.
.. . .. .. . ..
(b) (-) 3'-PhenoXybenzyl 1-(4-ethoxyphenyl)-2,2,3,3-
tetrafluorocyclobutane carboxylate
The resolved (-) acid, 0.2 g., was refluxed in thionyl-
chloride (1 ml) for one hour. After evaporation of
excess thionyl chloride, the residue was dissolved in
petroleum ether (b.p. 60 - 80) and added to 3-phenoxy-
benzyl alcohol (0.139g) and pyridine (0.238g) in benzene
(3 ml) and petroleum ether (3 ml). The reaction mixture
was stirred overnight, quenched with ice-water, washed
with water and the solvent layer separated and dried over
molecular sieve. After evaporation of the solvent the
pure ester was obtained as a viscous liquid by chromato-
graphy in silica gel using methylene chloride as theeluent. Yield 99.1~, 20 = -58.2.
EXAMPL~ 5
(a) 1-(3,4-methylenedioxyphenyl)-2,2,3,3-tetra~luoro-
cyclobutane carboxylic acid
A mixture of ethyl 2-(3,4-methylene dioxyphenyl) propenoate
(2.2 g), tetrafluoroethylene (5 ml.), a-pinene (1 drop),
N-ethyldiisopropylamine (1 drop) and benzene (10 ml), was
heated at 150 - 155C for 24 hours then at 160 - 165C
for 16 hours, then cooled. The solvent was evaporated
to leav~ an oil (3.0 g). This oil was purified by
chromatography on silica gel using benzene as eluent to
give 1.4 g (44%) of ethyl 1-(3,4-methylene dioxyphenyl)-
2,2,3,3-tetrafluorocyclobutane carboxylate.
The ethyl ester was hydrolysed by refluxing for 2 hours
- 30 with a mixture of potassium hydroxide (5 g), water (50 ml)
and cthanol (50 ml). The ethanol was removed by
I 1S7771
- 17 -
evaporation and the aqueous residue extracted with
diethyl ether. The aqueous layer was acidified and the
precipitate filtered off, dried and recrystallized from
petroleum spirit (b.p. 60 - 80)/ diethyl ether to
yield 0.9 g of the acid as white crystals m.p. 168-9 C.
Analysis: C 49.62%, H 2.72~, F 25.8%.
C12~l8F4O4 requires 49.33%, H 2.76~, F 26.o%.
(b) 3'phenoxybenzyl 1-(3,4-methylenedioxyphenyl)-2,2,3,3-
tetrafl~orocyclobutane carboxylate.
.
The acid prepared in Example 5(a) (0.5g) was mixed with
thionyl chloride (1 ml) and refluxed for 45 minutes.
Excess thionylchloride was removed under vacuum. The
residue was dissolved in petroleum spirit (b.p. 40-60)
(5 ml), and added over 5 minutes to a stirred mixture of
3-phenoxybenzylalcohol (0.4 g), pyridine (0.5 ml),
benzene ~15 ml) and petroleum spirit (b.p. 40 - 60)
(15 ml). After overnight stirring at room temperature
the mixture was added to ice water and extracted with
diethyl ether. The ether extract was washed with dilute
hydrochloric acid, water, sodium bicarbonate solution and
dried over anhydrous sodium sulphate. Evaporation of
the ether left an oily residue (0.78 9) which was purified
by chromatography on silica gel with benzene as eluent
to yield 0.7 g of the 3-phenoxy benzyl ester as a clear
yellow oil.
Analysis: C 63.54~, H 4.01%, F 15.9%.
C25H18F4~5 requires C 63.30(~ l 3.82~, F 16.C~.
EXAMPLES 6 to 20
.
Using the general method set out in Example 3,
the compounds listed in Table 1 were obtained from the
appropriate starting materials.
l lS7771
- 18 -
Analysis,spectra and other characterising data
were consistent with the stated structures.
Table 1 includes the compounds of Examples 1, 2,
3, 4 and 5 for ease of reference.
1 157771
-- 19 --
TABLE 1
_ _
Example Rl R2 yl y2 y3 y4 y5 y6 ~3
No.
.
1 Cl H H H H H H H - (a)
2 C2H5 H H H H H H H (a)
3 C2H50 H F F F F H H (a)
4 C2H50 H F F F F H H ~a)
-0-CH2-0- F F F F H H (a)
6 CHF2cF2-o- H F F F F H H (a)
7 C2H50 H F F F F H H (c)
8 Cl H F F F F H H (b)
9 C2H50 H F F F F H H (d)
C2H50 H F F F F H H (b)
11 Cl H F F F F H H (a)
12 CH30 H F F F F H H (a)
13 -0-CH2-0- F F F F H H (c)
14 C2H50 H F F F F H H (f )
Cl H F F F F H H (c)
16 C2H50 H H H F F H H (c)
17 C2H50 H H F F F H H (c)
18 Cl H F Cl F F H H (c)
19 Cl H F F F F H H (e)
C2H50 H Cl Cl F F H H (c)
21 F H F F F F H H (e)
22 C2H50 H F F F F F F (e)
Note* The compound of Example 4 is the R(-) optical isomer
of the compound of Example 3.
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EXAMPLE ~1
The biological activity of the new cyclobutane esters
was examined in a series of tests, the results of which are
collected in Table 2.
Insecticidal activity was investigated against the
common hous~ly, Musca domestica, and the sheep blowfly,
Lucilia cuprina. The methods used were as ~ollows:-
(i) Housefly
(a) ComPound alone
Tests were carried out using a standard DDT-susceptible
strain (~t~O/IN/l) of M domestica. The compound was applied
in an acetone solution by microsyringe to tlle dorsum of the
thorax of two day old female flies reared from pupae of
average weight 2.2 - 2c5 gm/100 pupae. The adult flies were
fed on water and sugar-only diet and maintained at 26C and
70% RH. The mortalities were counted at 48 hours aftér
treatment and compared with acetone-treated controls. Flies
unable to move or stand normally were considered dead. The
LD50 value was obtained from a logit computer programme
based on three replicates of 10 flies at each dose level.
The LD50 value for DDT determined under the same
conditions was 0.26 l~g/fly.
(b~ Potentiation
The compound was also tested on the insects described
above in conjunction with the potentiator "Sesoxane" by
pretreating the insect with 1 ~9 of the potentiator in
acetone.
The mortalities were counted at 48 hours a~ter treat-
ment and compared with acetone and acetone/potentiator
controls.
The LD50 value was determined as described above.
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For DDT, with the same potentiator the LD50 value was
0.24 ~g/fly.
~ bout the same levels of po,entiation were
obtained when "Sesoxane" was replaced by an ecual
amount of piperonyl butoxide.
(c) Insect Repellency
Repellency tests were carried out on the same
strain of housefly as in the ~ortality tests. Female
flies at least two days old, not previously fed protein,
~-ere taken the day before the test, anaesthetized with
C2 and counted into holding containers of twenty flies
each. These were supplied with water and solid sucrose.
On the day of the tests the food and water were removed
in the morning (0900 hr). As the tests were
performed only between 1200 hr and 1730 hr, the flies
were therefore starved for a minimum of three hours
before testing.
The test involved the use of attractant baits
to which the candidate compound was a~plied. These
were exposed to the flies and the number of flies
landing on each bait counted. The baits consisted of
aluminium caps of area 5.94 cm filled with bakers
yeast mixed with water and slightly heated to form a
solid surface film.
Eight lots of 20 flies were used in a run in
which seven discus were treated with a graded dilution
series of the test chemical using acetone as solvent,
together with one disc treated with acetone as a
control. The concentrations of the compound ranged
from 0.031 ~g/~l doubling at each level up to 2.0 ~g/~l.
One hundred microlitres of each solution was pipetted
evenly over the surface of each disc and left until the
acetone had evaported.
The flies to be used were released into
standard 205 mm x 205 mm x 255 mm mesh ca~es and left to
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acclimatize in the test room maintained at a temperature
of 26C + 1C and humidity approximately 60%, for ten
minutes before introducing the treated discs into--each
cage. Before use the discs were marked on the reverse
sides and then randomly mixed to avoid bias in counting.
In the thirty minute period of the test the number of
flies on the surface of each disc was counted in the
first and second minute after introducin~ the baits
and thereafter every two minutes. In this way sixteen
counts were obtained for each concentration, the
totals of which ~ere then used or a regression
analysis of the concentration effect. Also a total
number of landings for each concentration was obtained
and used for calculation of the Index of Repellency
(IR). All replicate tests were carried out with fresh
flies and baits, and the compounds were tested in three
replicate runs.
The total number of flies counted on each
disc for the seven concentration levels was su~med and
averaged. In the following formula this figure is
designated (N), where (C) equals the number of flies
counted on the control:-
C - N x 100 = Index of Repellency (IR)
C ~ N
(ii) Sheep Blowfly
(a) Insecticidal Activity
_
The compounds were tested for activity
against a dieldrin susceptible strain (LBB) which had
been collected before dieldrin usage in the field.
The test compound was applied in acetone
solution, 0.5 ~1 dispensed with a Drummond micropipette
to the dorsum of the thorax of 2-3 day old females.
Adult flies were fed on water and sugar-only and
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maintained at 25 C and 60 - 70~O RH. The mortalities
were determined after 24 hours. Moribund flies were
regarded as dead. The LD50 values, in terms of
concentration, were interpolated from a probit/log
dose graph using a compu~er program.
Comparative LD50 figures for DDT and dieldrin
are 0.17 and 0.025 ~g/insect.
(b) Potentiation
Potentiation with "Sesoxane" was
investigated as described above in the housefly tests.
(c) Repellency
Repellency was determined as described above
in the housefly tests, except that the baits consisted
of an agar gel containing fresh beef blood.
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TABLE 2 INSECTICIDAL ACTIVITY
Compound of Sheep Blowfly
Example No. (Lucilia cuprina)
LD50LD50 with synergist Repellency
~g/~ insect ~g/~ insect n ex
1 ' 1.78 0.04 36
2 0.77 0.06 61
3 0.05 0.001 79
4 0.024 O. 00026 73
0.04 0.003 66
6 0.40 O. 04
7 O . 02 O . 0004 62
8 0.023 0.0023 77
9 0.11 0.03 88
0.03 0.003 78
11 0.05 0.007
12 . 17
13 0.03 0.001 68
14 0.14 0.009 42
0.18 O. 006
16 a~10 0.~ OQl
.17 O . 14 O. 002
18 O. 14 O. 001
19 o.n28 O. 0~2
~ ~ Q OQ2
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TABLE 2 INSECTICIDAL ACTIVITY (continued)
_ ._
Compound of Housefly
Example No. (Musca domestica)
LD50LD50 with synergist Repellency
~g/Ot ~g/~ insect Index
insect
1 1.8 0.2 49
2 1.32 0.22 81
3 0.13 0.003 81
4 0.10 0.005 86
0.26 0.017
6 0.6 0.036 12
7 0.18 0.065 89
8 0.55 0.01
9 0.58 0.05
0.13 0.005 84
11 0.34 0.018
12 >32 0.24 18
13 0.12 0.018 78
14 0.07 0.005 65
Q.26 0.6
18
2~
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E ~PLE Z
-
The following are examples of insecticidal
compositions in accordance with the invention. All
parts are by weight.
(a) Spray formulation
The following composition is adapted for spray
application.
Compound of formula I 4.0
"Sesoxane" or Piperonyl
butoxide1.0
Deodorized kerosene 79.4
Alkylated naphthalene 16.0
(b) Aerosol
The following materials are metered into a
suitable 'bomb' container sealed and equipped with a
valve in the usual way.
Compound of formula I 3.0
Potentiator 1.0
Methylene chloride 10.0
'Freon 12'* (trichlorofluo ~.ethane) 43-0
'Freon 11'* (dichlorodifluoromethane) 43
* Trademarks
