Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
~.Z3~5Z
CYCLOPROPYL CAR~OXYLATE COMPOUNDS, A PROCESS FOR THEIR MANUFACTVRE `
AND THEIR USE AS PESTICIDES
This invention relates to cyclopropyl carboxylate compounds pos-
sessing pesticidal activity, to a process rOr the manufacture and to
their use as pesticides. The compounds are related to the so-called ~ -~
synthetic pyrethroids.
United Kingdom Patent Specification 1,413,491 discloses, inter
alia, 3-phenoxybenzyl esters and alpha-substituted 3-phenoxybenzyl
esters Or 2~2_dimethyl-3-(2~2-dihalovinyl)cyclopropanecarboxylic ~-~
acids; it also disclo~es their u~e as insecticides. Whil3t the high
level Or activity Or this class Or compounds against in~ects i~ dis-
closed, no mention is made to their activity against Acarines such as
the Ixodidae family and the Tetranychidae Pamily.
The Applicant has now Pound a small group of 3-phenoxybenzyl
esters and alpha-substituted-3-phenoxybenzyl esters of
2,2_dimethyl-3-(2,2-dihalovinyljcyclopropanecarboxylic acids which
not only exhibit high level~ Or insecticidal activity but also have a
significant er~ect on acarines, for example Tetranychus urticae
(glasshouse red spider mite) and Boophilus microplus (cattle tick).
Accordingly the preqent invention provides cyclopropyl carboxy-
late compounds in the form Or single isomers or combinations thereof
20 and having the general formula:- X
c ~a ~ (I)
:
.
::~
- : . - ~ . ~ ,..... . ~ : , . - .
., : .. - ,, ~ . .,, , ~, . . . .
2 1~.Z34~
wherein X is a chlorine, bromine or iodine atom and Y i3 a hydrogen
atom or a cyano or ethynyl group. Preferably X i~ a chlorine atom.
From formula I it will be apparent that the compounds according
to the invention can exist in a number of stereoisomeric forms. Thus
in the acid portion of the compounds, the hydrogen atoms carried by
carbon atoms 1 and 3 in the cyclopropyl ring can be in a cis or trans
relationship and because of asymmetrical substitution at these carbon
atoms each cis i~omer can exist in two ~tereoisomeric rorms and each
trans isomer can exist in two stereoisomeric forms. The absolute con-
figuration of these four stereoisomeric forms can be satisfactorilyderined using the Elliott nomenclature as defined by M. Elliott, A.W.
Farnham, N.F. Janes, P.H. Needham and D.A. Pulman, Nature, 1974,
248, 710. Thus the four stereoisomeric forms are designated ~1R,
cis), (1S, cis), (lR, trans) and (1S, trans).
In the acid portion Or the compounds according to the invention
the possibility of further stereoisomeric forms occurs by virtue of
the asymmetric substitution of the vinylic double bond appearing in
the substituent at position 3 on the cyclopropyl ring. The most sat-
isfactory method o~ defining stereoisomerism Or this kind is the E~Z
nomenclature of J.E. Blackwood, C.L. Gladys, K.L. Loening, A.E.
Petrarca and J.E. Rush, J.A.C.S./90:2J1968.
In the alcohol portion o~ the compounds according to the inven-
tion, when Y represents a cyano or ethynyl group, a further site of
asymmetry occurs at the alpha-carbon atom carrying the Y-substituent
and the absolute configuration of this carbon atom may be designated
R or S in accordance with the sequence rules of R.S. Cahn, C. Ingold,
and V. Prelog, Angew. Chem. Int. Ed. 5, 385 (1966). It ~hould be no- ;,
ted that the Elliot et al nomenclature and the Blackwood et al nomen-
clature are both based on these sequence rules.
Thus the compounds according to the invention can exist in 16
stereoisomeric forms and, whilst all isomers or combinations thereof
come within the scope of the invention, it has been found that com-
pounds derived from a cyclopropyl carboxylate having a configuration
at carbon atoms 1 and 3 in one of the following forms:-
(lR, IS cis), or
(lR, cis)
-- ;
3 ~.Z34~Z
give rise to better activity in terms of their acaricidal and in~ec- ~ -
ticidal effects.
The cyclopropyl carboxylate of formula I may be prepared by
known methods. A convenient process is the reaction of a compound of
formula:-
X ',;;
H CH = C\
~ F (II)
CH3 / / \ \ COZ
CH3 H
with a compound of formula~
0_~/~ '`~ ''
Q - ~H ~ (III)
wherein X and Y are as defined hereinbefore; one Or the groups Q and ~ -
Z repressnts a halogen, preferably a chlorine or bromine atom, and
the other represents a hydroxy group. The reaction is preferably car- `~
ried out in the presence of a suitable base, for example a tertiary
amine such astriethylamine~ When a particular isomeric form of the
compounds according to the invention is required the appropriate ste-
reoisomeric starting materials should be selected. Alternatively
various isomers or isomer combinations can be isolated by physical'; ~ -~
separation techniques, e.g. fractional crystallization or chromato-
graphi¢ methods.
The compounds of the invention are of particular interest as
acaricides and insecticides and therefore the invention includes pes-
ticidal compositions comprising a compound according to the
invention, a surface sctive agent and/or carrier. The invention al~o
includes a method for combating acarid and/or insect pests at a locus
which comprises applying to the locus an acaricidally-active or in-
secticidally-active amount of a compound or composition according to
the invention.
25The term "carrier" as used herein means a material, which may be
inorganic or organic and of aynthetic or natural origin, with which
the active compound is mixed or formulated to facilitate its appllca-;~
3~52
tion to the plant, seed, 30il or other object to be treated, or its
storage, transport or handling. The carrier may be a solid or a
fluid. Any of the material usually applied in formulatine pesticides
may be used as carrier.
Suitable solid carriers are natural and synthetic clays and
silicates, for example natural silicas such as diatomaceous earths;
magnesium silicate3, for example, talcs; magnesium aluminium sili-
cates, for example, kaolinites, montmorillinites and micas, calcium
carbonates; calcium sulphate; synthetic hydrated silicon ox.des and
synthetic calcium or aluminium silicates; elements such as for exam-
ple, carbon and sulphur; natural and synthetic resin~ such as for
example, coumarone resins, polyvinyl chloride and styrene polymers
and copolymer~; solid polychlorophenols; bitumen; waxes such as for
example, beeswax, paraffin wax, and chlorinated mineral waxes; and
15 solid fertili3ers, for example superphosphates. :-
Examples of suitable fluid carriers are water, alcohols, such a~
for example, isopropanol, glycols, ketones such as for example, ace-
tone, methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone;
ether~; aromatic hydrocarbons, such as for example, benzene, toluene
and xylene; petroleum fractions such as for example, kerosine, light
mineral oils; chlorinated hydrocarbons, such as for example, carbon :
tetrachloride, perchloroethylene, trichloroethane, including lique-
fied normally vaporous gaseous compounds. Mixtures of different li-
quids are often suitable.
The surface-active agent may be an emulsifying agent or a dis-
persing agent or a wetting agent; it may be nonionic or ionic. Any of
the surface-active agents usually applied in formulating herbicides
or insecticides may be used. Examples of suitable surface-active
agent~ are the sodium or calcium salts of polyacrylic acids and lig-
30 nin sulphonic acids; the condensation products of fatty acids or ali- ~ :
phatic amines or amides containing at lea3t 12 carbon atoms in the -
molecule with ethylene oxide and/or propylene oxide; fatty acid
esters of glycerol, sorbitan, sucrose or pentaerythritol; condensates
of these with ethylene oxide and/or propylene oxide; condensation :
products of fatty alcohols or alkyl phenols for example p-octylphenol
or p-octylcresol, with ethylene oxide and/or propylene oxide;
.. - .. .- -
.
~ 23452
sulphates or sulphonates of these condensation products; alkali or
alkaline earth metal salts, preferably sodium salts, of sulphuric or
sulphonic acid esters con~aining at least 10 carbon atoms in the
molecule, for example, sodium lauryl ~ulphate, ~odium secondary alkyl
~ulphates, sodium salts of sulphonated castor oil, and sodium alkyl-
aryl sulphonates such as sodium dodecylbenzene sulphonate; and poly-
mers of ethylene oxide and copolymers of ethylene oxide and propylene
oxide.
The compositions of the invention may be formulated as wettable
10 powders, dusts, granules, solutions, emulsifiable concentrates, emul- -
sions, suspension concentrates and aerosols, and will generally con- ;
tain 0.5 to 95~ w, preferably 0.5 to 75S w, of toxicant. Wettable
powders are usually compounded to contain 25, 50 or 75% w, of toxi-
cant and usually contain, in addition to solid carrier, 3-10% w of a
dispersing agent and, where necessary, 0-10S w of stabiliser(s)
and/or other additives such as penetrants or stickers. Dusts are usu-
ally formulated as a dust concentrate having a similar composition to
that of a wettable powder but without a disper~ant, and are diluted
in the field with further solid carrier to give a composition usually ` ~!,
containing ~-10~ w of toxicant. Granules are usually prepared to have
a size between 10 and 100 BS mesh, and may be manufactured by
agglomeration or impregnation techniques. GenerallY, granules will
contain ~-25S w toxicant and 0-10% w of additives such as
stabilisers, slow release modifiers and binding agents. Emulsifiable
concentrates usually contain, in addition to the solvent and, when
necessary, co-solvent, 10-50% w~v toxicant, 2-20% w/v and 0-20% w/v
of appropriate additives such as stabilisers, penetrants and corro-
sion inhibitors. Suspension concentrates are compounded so as to ob-
tain a stable, non-sedimenting, flowable product and usually contain
1-75$ w toxicant, 0.5-15% w of dispersing agents, 0.1-10S w of sus-
pending agents such as protective colloids and thixotropic agents,
0-10% w of appropriate additives such as defoamers, corrosion inhibi-
tors, stabilisers, penetrants and stickers, and as carrier, water or
an orgaDic liquid in which the toxicant is substantially insoluble;
35 certain organic solids or inorganic salts may be dissolved in the ~;
carrier to assist in preventing sedimentation or as anti-freeze
agents for water.
The compo~itions of the invention may contain other lngredient~,
for example, protecti~e colloids ~uch as gelatin, ~lue, casein, gum,
cellulo~e ether~, and polyvinyl alcohol; thixotropic agent~ e.g. ben-
tonites, sodium polyphosphates; ~tabilisers quch as ethylene diamine
tetra-acetic a¢id, urea, triphenyl phoqphate; other herbioides or
pesticideQ; and stickerq, ~or example non-volatile oils.
Aqueous dispersions and emulsions, for example, compo~itions
obtained by diluting a wettable powder or an emul~iriable concentrate
according to the invention with water, al~o lie within the ~cope of
the preqent invention. The qaid emul~ions may be of the water-in-oil
or of the oil-in-water type, and may have a thick "mayonnaise"-like
con~istency.
The invention iq further illustrated by reference to the fol-
lowing Examples:-
5 Example 1 Preparation of (RS)alpha-cyano-3-phenoxybenzyl(1S,lR,cis)-
(E/Z)3-(2-chloro-2-fluorovinyl)-2,2-dimethylcyclopropane_1-
carboxylate
(1S,1R,ci )(E/Z)-3-(2-chloro-2-fluorovinyl)-2,2-dimethyl-1-cyclo-
propanecarboxylic acid (0.8g), (R,S)-alpha-cyano-3-phenoxybenzylbromide
(1.15g) and potasQiUm carbonate were stirred together in acetone
(25ml) for 4 hours at room temperature. The product waq treated with
water and extracted with ether (3 x 25ml). The ethereal extraats were
combined and evaporated to give a crude product which was purified by
chromatography u~ing Qilica gel and eluent of toluenehexanone 1:1 to ~
give the deQired product nD= 1.551.
Analy~iQ Calculated for C22H1gN03Cl F: C66.1; H4-8; N3-5
Found : C65.7; H4.9; N3.2
Example 1A Preparation Or starting acid for Example 1 ((1S,1R,ci~)
(E/~)-3-(2-chloro-2-fluorovinyl)-2,2-dimethyl-1-cyclo ~ `
39 propanecarboxylic acid)
Dichlorofluoromethane was dissolved in 100ml sodium-dried hexane
at 0C. The dichlorofluoromethane (7.2g; 0.07mol) ~olution wae added
with 3tirring over 20 minutes at 0 C under nitrogen to a fla3k con-
taining lOOml dry hexane, potassium tertiary butoxide (7.85g;
35 0.07mol) and triphenylphosphine (18.3g; 0.07mol). The flask was al-
lowed to warm to 15C and then a hexane ~olution Or
(1S,1R)-ciq-caronaldehyde methyl ester (10.0g; 0.064 mol) added
~ 2~
over 15 minutes. The nitrogen was removed and the flask heated at ;~
55C for 1 hour. The reactants were then aIlowed to stand overnight.
A brown precipitate was then filtered from a brown oil. The oil was
distilled to yield 9.2g of a colourless oil and by GLC this was ~hown
to be composed of starting aldehyde and 2 higher boiling components.
A saturated solution of sodium metabisulphite iD water was pre- ;
pared. To 50ml of this solution was added 35ml of industrial methyl~
ated spirit and then surficient water to ~orm a olear ~olution. Tbis
solution was added to an ether solution of the oil recovered above
and the mixture stirred at room temperal;ure for 0.5 hours. GLC
confirmed the formation of a bisulphite-addition oompound and
complete removal of aldehyde ~tarting material. The organio layer was
separated, washed with water, dried and evaporated to yield 3 3g of ~ -
(lS,1R,cis) (E/Z)-3-(2-chloro-2-fluorovinyl~-2,2-dimethyl-1-cyclopro-
pane carboxylic acid methyl e~ter (25S yield).
The ester t3.3g) was hydrolysed to the free acid usine ethanol
and 2N-sodium hydroxide to yield 2.6g acid (ô4S).
Examples 2-7
The following compounds were prepared using procedures -~imilar
to those shown in Examples 1 and lA (see Table I). ~-
CN ~l
~'
.'' ,'.'`,
. .
3~5~
TABLE I
CONFIGURATION AT
EXAMPLE Y _ _ _ __ REFRACTIVE
C and C C Double INDEX
1 3 alphaBond
_ _ . .
2 N (lS,1R,ci.~) _ E/Z nD 1.555
3 H ~1S,1R,tran~) _ E/Z nD 1-553
. .
4 CR ~1S91R,trans) (B,S) E/Z nD 1.552 :~
CN (lR,ci~) (R,S). E~Z nD 1.550
6 N (lR,cis) _E/Z nD1 1.553
C-CN (lS,1R,~i~) (R,N) E/Z _ _
~.~
(a) in the preparation of thi-~ compound the acid chloride ~-
of (1S,1R,cis)(E/Z)-3-(2-chloro-2-fluorovinyl)-2,2-dimethyl-
cyclopropanecarboxylic acid ~a~ reacted with (R,S)-alpha- ~
ethynyl-3-phenoxybenzyl alcohol in the presence o~ r
N-methylimidazole.
, ~
.23~Z
TABLE I (Cont~d )
_
EXAMPLE ANALYSIS
__ . ~
2 Calculation for C21H20o3clF C 67-3; H 5-4%
Found: C 67.0; H 5.4g
__ _ ___ _ __ . . . .
3 Calculation ~or C21H20o3clF C 6i-3; H 5-4%
_ Found: C 67.5; H 5.4%
4 Calculation for C22H1gNo3ClF C 66.1; H 4-8%
Found: C 66.6; H 5.1%
_ _. _______ _____ .
Calculation for C22H19N03ClF : C 66.1; H 4.8; N 3.5%
Found : C 65.6; H 4.9; N 3.2
__ . _ , ~
6 Calculation for C21H2003ClF C 67-3; H 5-4
Found : C 67.1; H 5.4%
_ ___ .
7(a)Calculation for C23H2003ClF C 69-3; H 5.1
Found : C 69.7; H 5.5
. _ __ _ . .. ~___ .. __ . _____
:, . . .
:''
;.
_ ~.Z3~5~
Example 8 Acaricidal activity of the cyclopropyl carboxylate composi-
tion
(a) Activity against one-host cattle tick, Boophilu~ microplus
(B.m.)
Two to three week old larval ticks were used. In the rearing
procedure calves were infe3ted with larval ticks which matured
over a three week period. Engorged adult ~emale ticks which
detach from the calf were collected and placed in 3" x 1 n gla99
tubes. Egg batches were laid by the females over the next ~ew
days and larvae e~erged three weeks later. The cyclopropyl car-
boxylates were formulated as solution3 or fine suspensions in
acetone containing 10% by weight of polyethylene glycol having
an average molecular weight of 400. The formulations contained
0.1~ by weight of the compound to be tested. lml of the
above-mentioned 301ution wa~ applied evenly to a filter paper
3ituated inside a petri di~h. After the paper was sufPiciently
dry it was folded in half and partly crimped along the outer
edge to form a packet. About 80-100 larval ticks (Boophilus
microplus) were transferred into the packet which was ~ealed
completely. The packets were placed inside an incubator, main-
tained at 27C and 80% relative humidity. After 24 hours the
packets were opened and the percentage of dead and moribund
larYae asses~ed. .;
(b) Activity against elasshouse red spider mite, Tetranychus urticaè
(T.u.)
The cyclopropyl carboxylates were formulated as solutions or
suspensions in water containing 20S by weight of acetone and -~
0.05~ by weight o~ Triton X100 as wetting agent. The formula-
tions contained 0.4~ by weight of the compound to be tested. ;~`
Leaf discs cut from French bean plants were held on moi~t filter
paper placed on a lid inside a waxed carton. Prior to te~ting,
each leaf disc was infested with 10 adult mites. Tbe mite3 and
discs were then 3prayed using a logarithmic spraying machine and
held under standard glas house conditions. After 24 hour3 the
percentage dead and moribund mites were a~sessed.
., ~ .. . .
~.;Z 3~2
1.
In (a) and (b) the concentration of material expected to kill 50~ of
the exposed group Or test speciea was calculated (LC50) and the toxi- -;
city of the compound waa compared with that of the standard
(parathion) and expresqed aa a Toxicity Index (T.I.)
LC50 of atandard
Toxicity Index = ~ X 100
LC50 of teqt Compound
The LC50 used for the standard in this calculation was the mean value
based on 20 determinations. The results are given in Table II.
For reasona of comparison, aimilar results are included for the
known compounds permethrin and cypermethrin which are disclosed in
United Kingdom Patent Specification 1,413,491 as Compound P21H and
Compound P 21P. :
......
~: , .- ~- .. .:.:, - .
.23~52
12
TABLE II - ACARICIDAL RESULTS
H CH - C~
>< ~V c~ ~ ~/
CH3 / ` ~ COO - CIH
CH3 H Y \===;/
. . _ . . ._ ~
COMPOUND CONFIGURATION AT . ::
EXAMPLE _ _ . __ _ ~ .
X V Y C1 and C3 Calpha DBunde ~:
_ .
1 Cl F CN (1S,1R,ois) (R,S) E/Z .
_ . . ., . _ ' ': :
Cl F CN (1S,1R,trans) (R,S) E/Z .
: ~ Cl F CN (1R,cis) (R,S) E/Z
_ . . .__ __ .. __ ,
: cypermethrin Cl Cl CN (1S,1R,cis, (R,S) _
trans) ~ :~
_ __ . __ _ _ _
2 Cl F H (1S,1R,cis) _ E/Z ::
__ . __ :
: 3 Cl F H (1S,1R,trans) _ E/Z
_ ___ __ __ ,~
: 6 Cl F H (1R,cis) _ E/Z
_. _ _ :. -"'~
permethrin Cl Cl H (1S,1R,cis, _ _
trans)
~ _ __ ... _ . .-- ::
Cl F -C_CN (15,1R,cis) (R,S) _ . : :
~ .:
.. ~
,:~ ,
; ~, ~ ,~.`,'
:: ~' ::.
: :'~ ."`.` -
.' ~, '- ,
~'
.,
13 ~L~23~52
TABLE II- ACARICIDAL RESULTS (Cont'd) : :
_ _ . _ __ _ __ _ __ _ __ ____
_ TOXICITY INDEX ~ :
EXAMPLE __ __ ~ _ __ _ ~ ___
Boophilus microplus Tetranychus urticae
__ __ _______ .
1 132 5
._____ ___. _ _
4 25 8
. . . _ , ..... _
560 10 :
.. ___ _ ____ _
cypermethrin 21 2
___ _ __
2 - 940 8
___ _ ____
3 65 3
_ _ .. ___ ,:
6 3150 26
_ __ ___ _ _ _ ___ ~. .
permethrin 223 1 ~;
_ _ ___
7 _ _ _ 16
~Z3~
14
It will be seen from the above re~ults in Table I that in the :~
Y=CN series, Example~ 1, 4 and 5 all possess superior acaricidal ac-
tivity over the known compound cypermethrin and that in the Y=H : :
series, Examples 2, 3 and 6 generally produce better results than the
corresponding known compound permethrin. Example 7 also produces
better acaricidal effects over permethrin and cypermethrin. :~
''~ ;':
~ '~ ..,'~.
; :.; .
