Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
~3~
-- 2
The present invention relates to esters oE 2,2-
dimethyl-cyclopropanecarboxylic acids substi-tu-ted in the 3
position of the cyclopropyl ring with a saturated or
unsaturated polyhalogenated chain of three carbon atoms, and
their use as insecticides. The invention also relates to
cyclopropanecarboxylic acids of -the above esters, -their
esters with lower alkyls and the synthesis processes
thereof.
The pyrethrins (or pyrethrum), that is, esters of
chrysanthemic acid (2,2-dimethyl-3-isobutenyl-cyclopropane-
carboxylic acid) with a retronolone (2-alkenyl-3-methyl-
cyclopent-2-en-4-olone), are insecticides of natural origin
having a rapid and high insecticide activity combined with a
low toxicity for mammals.
However, pyrethrum is easily degradable under
normal atmospheric conditions and this property makes
pyrethrum unsuited for the protection of agricultural
cultivations, limiting its use to indoor applications.
Furthermore, pyrethrum has a high cos-t due partly to the
complexity of the extraction processes and -to the exigency
of combining with suitable synergic substances.
In an attempt to overcome these problems, a great
number of substances structurally similar to pyrethrum
(pyrethroids) have been synthetized with a
,; ~
~:37~3~
~3=
view t;o oblaining a eompound wllich has tl~e insect.ieide
action all(l the lo~v to~ieity towar(ls mammals alld at tl~e
same -time is more resistallt to atmospheric conclitions,
see Ior example "Syntlletic Pyrethl-oids" (~!. Elliot-t Ed.)
ACS Symposium Series No. 42, ~Vashington 1977.
Researeh has been direeted towards tl~e
synt;llesis o new derivatives oI 2,2-dimethyl-eyclo-
propaneeall)oxylie aeicl ancl oI ancllogous substallces,
towarcds the syn-thesis of aleohols analogous to cyelo-
pentenolones, and to~vards ne~v groups havillg aleollolie
funetions to be esterified witll tlle derivatives or
analogues of 2,2-dimetllyl-cyelopropaneearbo~ylic acid.
Numerous derivatives of 2,2-~limetl1yl-cyclopropane-
carbQxylie aeid substituted in the 3 position l~ave
been obtained.
Amongst these the ~ost promising Irom tlle pOillt
of vie~v o r stability,- are those ~ icll earry in -the
3 position a ~,~-di-halovinylie group, see J. Farkas
et al., Chem. -Listy 52, 688 ~1958); M. Elliott et a].,
Nature (London~ 246, 169 ~1973); ancl ~l. Ell1ot et; al.,
J. Cllem. Soe., l~erkin 1, 1974, 2470.
Table 1 reeords some oL tl~c? syntlletic pyIetllroi(ls
tllat e~hibited interestillg propel~ties.
- ~
h ~L23~74L;3-3 ~: ~ ~
o
. ~.
U~
~, .,,
r~ b~
Q h , +~
td O h C~
h a.u'~
.~ ~1 ~
. ~ h c) ~ O ~S
,~
m ~ u~
r~ 0~
l l
~ ~ I .
~ ~:=o
.
, ~ .
CY) ~ ~ ~ ~ ~
. ~
_ _ I
(1) H
~ a a r,
.,. .,.
h S~
,5
~0
O ~. ~ Q~
_ _ . _ . .
~2~7~
.
~ a) ^ t" ~ o
h ~ (,-~ .~, +J
' `-- ~ t~ b~
a~ .~ o +~ o
o m
~ ~ s~ ; ~ t- ~ s
O ~ ~ ¢ C`J ^~ ~
rl ~ ' ~ ~
h ~ ^ -~ ~ ` U~
~1
~ c: ~ ~1 ^ c
t~ ~ ~ +~ C~ ` C`J
~ ~ ~ . I
S . ~ +~ ~
~ ~ +' C)+'
` ~ +~ - U) ~ O
S-~ 00 O S O r~ O,r~;
tl:) ~C~ +~
o a~ o ~ o
~ O E ~ t~
.D ~a) r~ O O U) ~, t_
~ ~
m ~ q f-~--'P1 f-
_ . .~
U ~ ~ ~ ur p~
~ O O O
a~
n
E~
E .~ r~
~ h
',~;
h h
~:
O
E ~d O ~ h
i h ~: E Q
O ' C) h ~
() (l) ~. a) ~.
_ _ __ . _
` ~ ~2~7~3~
. . E c
h O
~ ~'
~ U
~ ' C`J
5 1~
. ~ O
h O ~.
O
,, ~ a~
~ I~ rl ~
P h 1--
~ . ~ G~
m m
E ~
O E
~ C~
o . .
_.
~ ~ J
. .
= 7 ~2
It is an objec-t O:E tlle prcse~nt invention to
pl'OVide lleW COIllpOUlldS elldOIVed ~Vitil insecticidal
act;ivity .
ThereIore according to the present invention
there is provided an ester of 2,2-dimethy1-Gyclo-
propanecarboxylic acicl llaving tlle general :~ormul a:
3 \ / 3
/(: (I)
A - Cll - C~I - C - OR
O
ill ~VlliCII: I I
1~ represents CF3-C_C-, CY3-C=C~I- or CF3~ C112-
y
:in whi cll X represellts a hyclrogen, r1uorinc,
clllorine or bromine atom, and
Y represents a clllorine or bromine atom, and
P. rcpres~llts
-Cll~
R1 1~3 ll1
-Cll~ R, tl~e group -Cll- is boulld
z
to the 2 or 3 position,
. . . _ .
~37~3~
-- 8
R R
-CH2-C = C-CH2-R
or -CH2-C_C-CH2-R
in which Rl represents a hydrogen atom, -CN or -C_CH,
R represents a 3-phenoxy, 3-benzyl, 4-allyl or 4-
propargyl group,
R represents a hydrogen atom or an alkyl group and
is bound to the 2 or 3 position,
R represents a benzyl, benzoyl, phenoxy, allyl or
propargyl group and is bound to the 4 or 5 position,
Z represen-ts an oxygen or sulphur atom,
R5 and R6 independently represent a hydrogen or
halogen atom or CH3, and
R represents a phenyl, vinyl, substituted vinyl or
phenoxy group, with the proviso tha-t when A represents a
radical of formula:
X
CF3-~=CH-
wherein X represents a fluorine, chlorine or bromine atom, R
neither represents a radical of forrnula:
-~H- ~
R
wherein Rl represents a hydrogen atom, a -C~N radical or a
-C~CH radical and R represents a 3-benzyl, 4-allyl or 3-
phenoxy radical, nor a radical of formula:
, ....~
7~3~
- 8~ -
R3
~Z~
wherein R1 represents a hydrogen atom, a -C-N radical or a
-C~-CH radical, R3 represents a hydrogen atom or a low alkyl
group, and is bound to the 2 or 3 position, R4represents a
benzyl, phenoxy or allyl group and is bounded to the 4 or 5
posi-tion, and Z represents an oxygen or sulfur a-tom.
Advantageously, the invention relates to a
compound having the formula:
3 \ ~ 3
lS A - CH -\ CH - COOR
H
in which A represents CF3-C_C-, CF3-C=CH- or CF3-lC-CH2-
y
20and R represents
R
11l ~ or -C ~
O-CG1~5 113C CH2-C6}15
in which X and Y are as defined hereinabove and R
represents a hydrogen atom or -CN.
Preferably, the invention relates to a compound
having the formula:
~ ~,
~23~7~39
- 8b -
}i3C C113
\ / 1
C R
A - Cll - CH - COO - Cll ~
OC6H5
in which A represents CF3-C_C- and R1 represents a hydrogen
atom or -CN.
More particularly, the invention relates to the
~-cyano-3-phenoxy-benzyl ester of (~)-cis-2,2-dimethyl-3-
trifluoromethyl-ethynyl-cyclopropanecarboxylic acid, the~-
cyano-3-phenoxy-benzyl ester of (~)-trans-2,2-dimethyl-3-
trifluoromethyl-e-thynyl-cyclopropanecarboxylic acid or
mixture thereof.
Advantageously, the invention relates to a
compound having the formula:
~ - Cl{ - Cll - COO - Cii ~
OCG~15
in which A represents CF3-C~I-C~I-,and
R1 represents a hydrogen a-tom or -CN.
3~ More particularly, the invention relates to the 3-
phenoxy-benzyl ester of (~-trans-2,2-dimethyl-3~ tri~luo-
romethyl Z-vinyl)-cyclopropanecarboxylic acid, the ~-cyano~
3-phenoxybenzyl ester of ~)-trans-2,2-d.ime-thyl-3-(~-tri-
fluoromethyl-Z-vinyl)-cyclopropanecarboxylic acid or the ~ -
.
- 8c - ~2~439
cyano-3-phenoxybenzyl ester of (+)-trans-2,2-dimethyl-3-~B-
trifluoromethyl-E-vinyl)-cyclopropanecarboxylic acid.
Advantageously, the invention relates to a
compound having the formula:
\ / ~,1
A - Cl{ - Cll - COO - Cll
~
OC6115
in which A represents CF3-~-CH2-,
Y and X are as defined hereinabove and R1 represents a
hydrogen atom or -CN.
More particularly, the invention relates to the
~-cyano-3-phenoxybenzyl ester of (+)-cis,trans-2,2-dimethyl-
3-(2-chloro-3,3,3-trifluoropropyl)-cyclopropanecarboxylic
acid, the 3-phenoxybenzyl ester of (~)-cls-2,2-dimethyl-3-
(2-chloro-3,3,3-trifluoropropyl)-cyclopropanecarboxylic
acid, the 3-phenoxybenzyl ester of (+)-trans-2,2-dimethyl-3-
(2-chloro-3,3,3-trifluoropropyl)-cyclopropanecarboxylic acid
or the ~-cyano-3-phenoxybenzyl ester of (+)-cis,trans-2,2-
dimethyl-3-(2,2-dibromo-3,3,3-trifluoropropyl)-cyclopropane-
carboxylic acid.
Pre~erably, the invention relates to mixture of
the 3-phenoxybenzyl ester of (~)-cls-2,2-dimethyl-3-(2-
chloro-3,3,3-trifluoropropyl)-cyclopropanecarboxylic acid
and 3-phenoxybenzyl ester of (+)-txans-2,2-dimethyl-3-(2-
chloro-3,3,3-trifluoropropyl)-cyclopropanecarboxylic acid.
Advantageously, the invention rela~es to 2,2-
~'
~P~
~37~3~
- 8d -
dimethyl-cyclopropanecarboxylic acids and esters of the
general formula:
3 \ ~ 3
,C (II)
~ - C}l - C~l - COOR'
in which R' represents a hydrogen atom or an alkyl group
having 1 to 4 carbon atoms, and ~ represents a radical of
formula CF3-C_C- or a radical of formula CF3-CH=CH- or a
radical oE formula CF3-C-CH2-
y
lS wherein X represen-ts a hydrogen, fluorine, chlorine or
bromine atom and Y represents a fluorine or bromine atom.
Preferably, the invention relates to-
- a compound of formula:
~ C
CF3- C - C - Cll - Cl{ - COO~'
in which R' represents a hydrogen atom or an ethyl group; or
- a compound of formula:
\ /
/c
CF3 - Cll = CH - C~l - Cll - COOR'
in which R' represen-ts a hydrogen atom or an e-thyl group; or
- a compound of formula:
..
~ ~3743~
- 8e -
~ ~ 3
X C
CF3 - C -- CH2 - CH - CH - COOR '
Y
in which X and Y are as de:Eined hereinabove and R'
represents a hydrogen atom or an ethyl group~
/
/
//
3~7~3~
Thc.~ compouncls oI gencrnl rormula I are ent10wecl
wil11 a high insecticicle as well as acaricic1e activity.
The compounds of formula I may be readily prepared
from derivatives of 2,2-dimethyl-cyc1opropanecarboxy1ic
acicl covered by the following genera1 formula (II):
~13C C113
(Il)
C - 01~ '
in whic11 ~' represents a hydrogen atom or allcyl group
havi1lg l to 4 carbon atoms and ~ ls as deri1lec1 above,
by converti1lg compound II to the corresponcling acyl
halide which is then reacted with an alco1~o1 oi` the
general formula R-OH in whic1l R is as definecl above,
in an inert solven-t in the presence of an ha10gen1lydxic
acid-acccptin~ base. The compounds o~ rormula II are
believed to be novel.
One ol the processts ~or the preparation of the
derivalives of ge1leral folmula (lI), is conc1ucte(1
~ starting rrom polyi`luoro halogen.1tecl eth.1lc~s Or the
rO I~mu l~:
CF3 - C(X)Y2
in whic1l X and Y are as clefined a~ovc, allcl follows tht,~
reaction scheme l:
`- 8 ~3~3~
o \ /1
o C~ I
~ ~ , ~
u m N ~_
'-- 1' 1
U (~ ~ h r -
~) ~) O
1~ O
3;~
O ~ / ~
Q 8 t,
~, ,~ ~
a~ ~ 8 u ,~
~ ~ 11 o
U ~ ~ X~ U
3 ~ U h~ \ U
~C`l ~ (~
C~ U 1 ~7 ~ \>
X ~ ^ 11
P~ I I
_, I _, ~
c~ h
,~ h ~.)
E
~::
v~
=01 -
=lt= ~37~
1 ) /kldi t i on o r a CF3-C( X)Y2 coml)oullcl to tlle douL) le
)011(l Or ~ tt-'r O.r 3,3-d~ tlly~ p~lltt~lloic ~ t~
tht? pleserlce Or -ïrce raclic. 1 initiators, .ac:corclillg to
t he equ a t i on
O X
CF 3 - C ( X ) Y 2 ~01~ ' 1 ~JI`o 1
Y y
2) Cyc1izatic>n Or the adcluct thus obt;lillecl in tl
presence O r a base
X b ~ \/
C~3- 1 1 OR (_~ly~ CF3- l -Cl12 COO~ ' ( I I I )
Y Y
3) Dellydroh~logenation by rurtller treatmellt ~vi tb a base:
X ~ COOR' ~ CI~l3-C(x)-c~l X-- COOl~ ' ( IV )
(II)
Depenclin~ On tlle conclitions under wllicll tlle last Iwo
reactions ial't' carried out and on tl~e nature oï tile ha1Ogen
Y, stage 3) m<-y be acllievetl as stage ~) goes on, or may
evc?ll pr~cecle it accorcling lo tlle rOl lO~Villg St~tlllell(`eS:
~:3'7~3~
o o
C~3 - C /~ O~' ~ CF3~C(X)=C~I~OR'
y -IIY Y
~l -IIY l -llY
C~3 - I /~\n' ~ (IV)
~VIIen X represents a ha1Ogen in the compounds o.~ ~eneral
formu1a IV, the compounds may be subjectetI to a Iurtller
dehycIroIltIlo~ellation reaction according to lhe ecl~Iation:
4) CF3-C(X)=CI! /\ l~a~ F C C /\ COOI~
( IV) (V)
~lso this latt:er reaction, iI wisllecl, may be carried out
togcther ~vith stages 2 ancl 3, ~vithout isolating the
co~ )ou1lds oL genera1 formula IV.
TIIc? starting compoun(ls oL thc typc CF3-C(X)Y2
are nll kno~vn procIucts, retIdily obtainill)le .îrom lIalog(?ll-
at~cl polyfluoro etl ancs available on the marIcet, by means
of convcntioIlal rearraIlgcment rctlcti ons .
I;,~;amI)les oL compouI~ds Or tIIc ty~e CF3-C( X)Y2
i ll C
~L~3~,~9139
CF3-CFBr2
CF3-CBr3
CF3-CClBrz
CF3-CHClBr
CF -CC13
Suitable promoters of addition reaction 1) are the
organic peroxides, e.g. ter-butyl peroxide, benzoyl peroxide
or diacetyl peroxide, azo-derivatives, e.g. azo-bis-iso-
butyrronitrile, complexes containing transition metals, e.g.
those formed by iron or copper salts with aliphatic amines,
and Redox-transfer systems.
Reaction 1) is conducted by reacting, in the
presence of catalytic amounts of one of the above free
radical promoters, the polyhalogenethane with an ester of
3,3-dimethyl-pentenoic acid, preferably in a molar ratio
polyhalogenethane/ester greater than 1, at temperatures from
50 to 200C.
The reaction may conveniently be carried out in an
autoclave, under autogenous pressure, or at atmospheric
pressure, in inert solvents under reflux temperature.
The cyclization reaction 2) occurs under the
action of a strong base, such as alkaline alcoholate or
sodium hydride, in a polar solvent and at temperatures ~rom
-20 to t50C.
-
237~3~
~ prolonged treatment ~vith the same base or
uncl(!r s1i~hl,ly more draslic tempeliature eonditiol)s may
eause the Iurther clehyclrollalogellation aeeordin~ to
equation 3) and, ~vhen X is a halogen atom, aeeording
5 to equation 4).
/~ltc?rllatively, tllt~ elim~ tio~l r~a~tiO1l O:r tll(?
llY acicl may be carried ollt berole ~hc-,~ cyc'li~,atioll stn~e,
by the aetion oE inor~anie bases or oC aeicl-~eeeptor
amines.
The compoutlds preparecl according to the proeess
above deseribed, in general are ethyl esters er metllyl
,ing
esters irom wlliell the eorresponcl/aeicls are e;-sily
- obtained by eommon hydrolysis rC,~aCtiollS
~Yl~en the elimination reaetions oL` the llY aeids
-15 ancl of l-IX aeicls are earried out with inor~allie bases sueh
as sodium or potassium hydroxide, thc,~re is simultaneou~;
hydrolysis oI the t?ster ~roup so that, by a subseqent
aeidiIieatioll, the eompoullds are obtaint?tl direetly in lh(?
Iorm of Iree aeicl.
Com~oun~s Or formula II ean also be prepared
aeeordin~ to anotller proeess in l;h(? rirst sta~e Or ~vhiel
a COmpOUIlCI Or Iormula CF3CXY2 is addecl to an ~ster of
2-alkoxy-earbonyl-3,3-dimethyl-4-perltt?noie aeid or the
Iormula
=]5= ~237~3~
CII2 CII C(CII3)2 ICI~ COO~
COOR'
in ~vhich E~', X and Y are as defined above.
The subsequent stages develop in difLerent ~ays
depending on the A substituent that one wishes to get
in the 3 pos.ition ol the cyclopropylic rillg. The
starting compoulld (2-alko~y-ca:rboIlyl-3,3-tlillletllyl-~-
pentenoic ester) can be readily oht;ained by tl~e reactio
of 3-chloro-3-metIIyl-butelle (1) and a malollic ester,
see Belgian Patent Speci~ication No. 851,52~.
The lol].owing reactioIl scIIeme summarize~ the
steps whicll lead to the synthesis of the compouncls Or
gell(!ral Iormula II.
.. . . . ~ .. . .
:
(:~ O ~ ~ ~)~A
C~3 C_)
O ~ I _,
$ ~ ` 'I
C`l
,_ ~_) ~
X
~C ~
~ X ~
~ , C~ O -
U ~ C) I O ~1:
~ ~ ~ ~ ~ O
\ I ~ ~ ' I O
(_) V
\ / I
C~ ~ O , C ,)/ \
\ / I F~
C" / X
F~ \ ~ O ~;
~ 1 1 $
,~ v~ v ~, / ~
~ ~ ~ c`l
~ o c~ - ~ ~
Q~ O I +
::~ v ~
o ` - x
5, 5: v
v l ~
` ~
C`J F~ ,
V
.C ~ ~ Ci:;
4~ v ~ o -
~ l o ~;
~ v ~ ~ v o
u~ ~ ~ v v - ~
aj N ~ V
cd ~ _ ~_,/ \V
C~ O ~ ~ C,)
V ~) V ~ ~)
V V--~ ~
V \ / I _~
~L ~ V
C`J C~
E ~ I V V
.~: I V~ V~
~r~J o ~:
-
~2~'~43~
=l /:
~ C\l o
o o o
o ~ C~ ~,
. o
~, o ~ ~
VV--V V V
\V/ I > \~,/ I
V \~ (~) V/ \~
,
` V ~
V V
,
C~ V
~ .
~ o
o - ~ o
o
'~ o V
~ I o I ~ ~
V~,_~ V V
\v/ I
/ \~ / \~
V ~ ~ V (~
,. :~V X V
o ., V
U
c~l h h
E~
aJ
,.
U)
:~3~43~
- 18 -
The various steps summarized in scheme 2 will now
be explained in detail.
Reaction 1 (scheme 2)
Reaction 1 is conducted in the presence oE free
radical initiators such as organic peroxides, e.g. terbutyl
peroxide, benzoyl peroxide or diacetyl peroxide azo-
derivatives, e.g. azo-bis-isobutyronitrile; complexes
containing salts of transition metals, e.g. those formed by
iron or copper salts with aliphatic amines; and redox-
transfer systems.
Reaction (1) is conducted by reacting, in the
presence of catalytic quantities of one of the above free
radical initiators a polyhalogene-thane of formula CF3-CXY2
with an ester of 2-alkoxycarbonyl-3,3-dimethyl-~-pentenoic
acid, preferably in a molar ratio polyhalogenoethane/es-ter
greater than 1, at temperatures of from S0 to 200C.
The reaction may be conveniently carried out in an
autoclave, under an autogenous pressure or under atmospheric
pressure, in inert solvents at reflux temperature.
Examples of compounds of the CF3-C(X)Y2 type are
CF3-CFBr2
CF3-CBr3
CF3-CClBr2
_,~
, . . .
37~
CF3CllClBr
C1~3-CCI3
Reclction 2 (sch(?me 2)
Is carried out by treating the~ adduc-t obtained
by reaction 1 (B) with an eql1ivalent oI an alkaline
b~l~e (Nall~O3, Na2CO3, 1~2CO3, KOE~ O~I, C2115ONa), ill
an organic solvent to yield the diester of l,t-cyclo-
propanedicarboxylic acid indicatecl by thc lettcl (C)
in scl~eme 2. Starting from compound (C) there are
several routes to modify the polyhalogcllated ch.lin in
the 3 position oi -the cyclopropylic t`illg ancl fon carrying
out the decarboxylation.
Reaction 3 (scheme 2)
-
The cyclopropane derivative obtained in step 2
is dehydrollalogenated by treatment ~vith one equivalent
oL an allcaline base, the lat-ter bcing prelerably a
sodium alcoholate. ~ptionally, the same type Or
intermediate may be obtained directly starting fl-om the
adduct dcscribed in s-tep 1, by treatlllcllt ~vith t~vo
c(luivalellts of an alkalinc basc.
The resulting compound is tlle cyclopropanecli-
carboxylclt;c indicated by the letter (D).
Reactioll ~1 (scheme 2)
Compound D is Lurtller dellydrohalc)gella-tecl (~vllen
X=Cl, Br) by treatment ~vith an excess of a base,
3~3~
preLerably an alkaline alcollolal;e, or by Na~ll2 in an
orgallie solvent to yield intermediate (I,).
Reactioll 5 (scheme 2)
-
Cyclopropanedicarboxylate (C) is subjected to
hydrogenation by the aetion of zinc powcler ln hyclro-
chloric acid, in aeetie aeid or in methyl- or ethyl
aleohol, thereby obtainillg intermecliate ~F).
This reaetion is earriecl out Lor eomponllcls ln whieh
X = Cl, Br, and results in the introduction Or a
hydrogell atom in plaee of tlle halogen a~om i . e . ill
the resulting eompound X = Il.
Reaetioll G (seheme 2)
Intermediate (F) is subjeeted to clehydrollalogen-
ation uncler the same reaetion eonclition~ of reaction 3,
thereby obtaining intermediate (G) \vhich can also
be obtained by catalytie hydrogenation (Re.lctioll 7,
scheme 2) of the triple bond oL the ehaill in the 3
position of the eyclopropylic ring of intermediate (~).
The catalytie sy-stem used in reaction 7 may be chosen
Lrom amongst those eonventionally used for selective
reduetions of the triple bond to doubl(? borlcl, e.g.
Ilyclrogen 011 poisoned palladium c~talyst; Na/NII3 liquid;
hydrobol.lt;ioll :rollowed by llydro.lysis wit.ll ~ )h~t:ic
aeicls, see~ Tetraheclroll 1977, 33, page 18~5.
~3~3~
The above describt?d reactiolls yield the various
cyclopropanedicarboxylatt?s (C, D, ~, ~, G) ~vhich nlready
possess in tlle 3 position the polyhalogenated chains
corresponding to the differen-t meanings of substituent
~ in general formula II. These compounds may be
decarbo~ylated (Reaction 8) to oltain the clesirecl
compoullds o~ gent?ral Iormula II
l~eaction 8 (scheme 2)
The intermedia-tes (C, D, ~, F, G) are subjected
to decarboxylation ullder one or tlle othe~r of the
follo~ving conditions
8a) total or partial hydrolysis witll acicls or alkali
in alcohol, follo~ved by heatitlg o~ the carrespond-
ing acids in neutral or basic orgallic solvents,
at a temperature from 100 to 250C,
8b) hydrolysis as in 8a), follo~ved by heating in
quinoline in the presence of copper, at a
tempt?rature ~rom l00 to 250C,
8c) heating in aprotic polar solvents, e g climethyl-
sulphoxicle, in the presence O:r alkaline haLides
or cyatlidt?s, and stoichiolnetric quantities oI
wa~er (2 etluivalellts),
to yiel~l the compounds of gene~ral Cormula II in the
Iorm oC carboxylic acids (R = ~ rom which, it is
po~ssibl~ to prepare the correspondillg esters by
-
='J2= ~74;~
conventiona1 esterification reactiol-s, or in the -orm
Or esters rrom wllicll, ir wished, it is p(>ssil)1e t;o
prepare the corresponding acids by means o-f conven-~;iona1
hydrolysis reactions.
Thc ollowing Table 2 summarises tl~e reactions
which 1ead to -the di~Eer~nt compounds oL general
~ol~mula II, according -to the reaction schen)e 2.
Tab1e 2
Reactions Eor ~he preparation o:E compounds o:E the iorn)u1a:
\ /
/('
A - Cll - Cll - COOR'
in which R' reprcsents a hydrogen atom or an alkyl group
having 1 to 4 carbon atoms.
Su~s~ituent A Reactions
CF -C-C- l - 2 - 3 - ~ - 8
CF3-CX=CII- 1 - 2 - 3 - 8
CF3-CI-I=Cll- ~1 - 2 - 5 - 6 - 8
(X = ~l) ~1 - 2 - 3 - 4 - 7 - 8
_ __
CF3-CXY Cll2 1 - 2 - 8
, ~ . . . ~
=,'3~ 37~3~
The compounds of gelleral :rormula I may readily
be obtained Irom tl~e cyclopropanecarboxylic acids and
esters oI general formula II using routes ~vllich are
conventiollal in the practice of organic chemistry.
For example, the acids and es-ters Or general
formula II may be converted into tlle corresponding
acyl halides whicll by reaction witb alcohols of formula
R-0~l, in \vhicll R is as defined with respect to tlle
general formula I, yield the compounds O r g~neral
lormula I.
~`he gc,~neral s-tructure oI lhe acicls nncl esters
Or general lormula II embraces various geometrical
ancl configurational isomers whose existence is due to
the presence of the following factors:
tl~e asymmeLric nature oI carboll atoms in the 1 and 3
positions O:r the cyclopropyl ring (enantiomers);
relative spacial disposition ol COOR' group and of
su~stituent ~ ~vith respect to the planc loc~ted by
tlle cyclopropyl ring (cis or trans);
cis or tralls isomery of the subsLituellts present on
tlle dou~le ~ond in tl-e case in tvllicll ~ = CI~`3-C=CII-.
X
The sep.lration Or the val~lous iSOIllel~ mi.~;tulcs
in the various stereoisomers ancl in tlleir enalltiomers
may be acllievecl by applying kno~vn chelmical ~ecc~ iclues,
37~3~3
e. g. ehromatograpllie mc-thocls ancl, respeetively,
preeipitati.on O:r salts with optieally aetlve bases.
The present invention extends to tl~e isolation ancl USe
Ior tlle syntilesis of the eompouncls o general lormula I
ol all sterie and/or eon-Liguratiollal isomers obtainable
from the mixture Or eompounds of formula II prepared
as deseribecl above, as wc?ll as to tZIe use. O:r the nlixtules
them.~;elve~ alld o:L l;l~ose der.ivecl rrom thei r p~ ti.l I or
eomplete separation into stereoisomers.
Simi larly, -tlle eompollncls oL general i`ormll l.a I,
owing to tlle presenee oI asymmetry eelltres and Or the
possibility oL cis-trans isomerism, may also be mi.Ytures
Or isomers. A ellaraeteristie oL these mixtures is the
faet that the separation oI the eomponents may be earried
out by simple ehemieal teehniques, e . g. eolulllll ehromatograplly
or t h i n l aye r C11 r oma-t og r aph y .
Tl~e present invention also eml~raees the .isolation
and the use as inseetieide of eaeh stereo or eonrigurational
isomer as well as the direet use oL the mixtures obtai ned
by the synl;hes.is or by ineompletc? sel)aratioll Or the iSOlllCI'S.
Tl~e c:ompounds oL general Iormula I l~aVe a very
lligll aeti~,~i ty against inseets oI the type wllicl~ .Ire
par-tieular pests in the agrieultural ancl clomestic L:ielcls,
e.g. Ilc?llliptera, lepidoptera, eoleopteIa, cli.pter.l and
blattoidc?a ancl also exhibit a satis:rying acaricicle aetivi ty
~237~3~
that is clerinitely superior to thclt ol many Icnown
pyrethroicls.
The advantages oL tl~e compounds of the :inventio
are particularly evident if one considers the high
level of insecticide activity observed, togetller with
its low acute toxicity, as wili be seen ~rom tlle data
in Table 4 hereillafter, ~vhicll reports a ~omparison
tvitl~ two kllo~vn synthetic pyrethroids ancl :Erom ~xample 30
hereinaf~er. The pyrethroicls of tllis inven~ioll also
have good stability as is evidenced in E~ample 31
hereina.Etel .
'l'llc~ invention ~vill now be illustrated by the
following E~amples.
~xamplc 1
Preparation Or the intermedia-te ctllylester of 3,3-
dimeth~l-4,G-dibromo-6,7,7,7-tetrafl-lor-heptalloic acid
17 g of ethyl ester of 3,3-dimethyl-4-pen-tenoic
acid (0.105 mols), 55 g o-~ 1,1,1,2-tetlafluorodibromo-
etllalle (0.21 mols) and 0.5 ml of ter~utyl peroxicle were
loaclcd into an autoclave of 200 rnl llo~ding cap.lc:il.y in
a nitrogell atmosphe l`C .
Tlle autoclave ~vas tllell immersecl in an oil bath
and mecllanically shaken for 5 hours at a tempel.lture
of 120C. ~fter cooling, the contents ~vcre cliluted
~vith 100 ml o:E Cll2Cl2. l`he resultin~ solution was tllen
Z3~7L39
waslled with ll20 (3 x 50 ml) containing small quantities
of FeSO~, dried with anh~drous CaCl2 and the solvent
evaporated under vacuum. 43.3 g of ra~v product was
obtained wllicll was dis-tillecl under vacuum gathcring
the Iraction boiling at bctwen 97 and 99C at 0.25 mmllg.
39 g of ethyl 3,3-dimethyl-~,6-dibrc)mo-6,7,7,7-
tetrafluololleptanoate were obtained.
r;lcmental analysis:
Bromine: calculated: 38.~1%; found: 37.83%.
¢~ample 2
Prcparation of lhe c-thyl ester oL 2,2-dimethyl-3-(~-fluoro-
~-trifluoromethyl-vinyl)-cyclopropanecarboxylic acid
and o~ the rrce acid
Sodium ethylate solution (0.132 mols) in
ethanol (150 ml) was added -to a solu-tion oL e-thyl
3,3-dimetllyl-4,6-dibromo-~,7,7,7,--tetrafluoroheptanoate
(25 g, 0.06 mols) obtained as described in Example 1,
in ethanol (50 ml) at a temperal;ure oE Irom 23 -to 32C
undcr stirring.
On completion o~ thc adclitioll, the resultillg
solution \vas maintainetl at room tcml)cl~aturc? ~or 3 hours.
*llereupon, a 50 ml portion ~V.lS dla~vll from thc
solutioll and concclltratcd to a rcducecl volume~ Tlle
resultillg solution was thereupon poured into ~vater and
ice, The solution was then extractccl \vit;h C1l2Cl2 (50 ml)
=27= ~ ~ ~7~3~
alld tlle organic phase was waslled with water until
attaining a neutral plI, after whicll it was driecl witl
anllydrous CaCl2 and tI~e solvent was removed uIlcler
vacuum .
3.6 g of a raw reactlon product were obtainecl
which, aIlalysed by gas-chromatograplly coupled Wi'tll
mass spectrometry, proved to be precIominantly composed
of tlle ethyl ester of 2,2-dimetllyl-3-(fi-rluoro-~-
triIluoromethyl-vinyl)-cyclopropanecarboxyl.ic acid
(compouncl (a), Table 3) that was .isolatable l`:rom tt-le
raw product ~y column chromatograplly and of -tlle ethyl
ester of 2,2-dimetllyl-3-(~-bromo-~,y,y,y - tetrafluoro-
propyl)-cyclopropanecarboxylic acid (about 20~ of the
raw produc,t) (compouIlcI (b) Table 3).
llle remaining part of the ethanol solution,
from wllich the 50 ml portion had been talsen, was treated
witll 6 ~ Or ~OII.at 85% concentration in 30 ml Or ethanol.
The reactlon mixture was then heal,ed for 2 hours
at the re:i''lu.Y temperature in order to carry out tlle
llydrolysis of the ester ancl to complete the cIellyclro-
omillation Or tlle ,B-I)rolllo-~ ,y ,y ,y-tetrarluorol)ropyl
~roup. Tllc~ reaction mixture was theIl coIlccntr~ted aIld
poure~l int.o water and ice~ Thc IlliXt,Ul`C was a(':idi f1cd
w1t,h dilute II2S04, then cxtractcd with CII2Cl.2 (3 x 50 ml)
ancI tl~e or~anic phase w~s theIl wasl~ed witll an aqueous
- ~x=
~3743~
solution o~ NaCl (2 ~ 100 ml) and dried Oll anlldyrous
CaCl2.
l'he solvent was removed under vacuum tllereby
obtaining 8 g oI 2,2-dimctllyl-3~ fluoro-~-trirluoro-
mcthyl-villyl)-cyclopropanecarboxylic acid in the -form
of a viscous straw-yellow oil (Compound (c), Table 3).
Example 3
~rcparatioll oI the intermediate 3,3-dimet:llyl-,~ ,6-
tribromo-7,7,7-triIluoro-llcptanlc acid ethyl est;er
13 g of ethyl ester of 3,3-climethyl-4-pelltelloic.
acicl (0.083 mols), 53 g O:r 1,1,1-tri1uoro-2,2,2-tri-
bromoethane (0.1~6 mols) allcl 0.5 ml o:f -tert-butyl
peroxide were loaded into an autoclave witll a holcling
capaci-ty of 200 ml in a nitrogen atmospl~ere.
Tlle autoclave was thereupon placed into an
oil bath and mechanically shaken for 5 hours at a
temperature oL 120C and ~or 1 hour at 130C. ~rter
cooling, tlle contents were dilutecl wit:ll 100 ml ol`
methylenc cllloride. The solution was then washed with
water (3 x 50 ml) containing small qualltities ol ferrous
Sllll)llat(~ nd driecl 011 arll~y(lrOUS CaCI.2. t~l`tCI- ('J.illlillat:iOIl
of tElC S-)lVellt by evaporation, I;llc ~a\v plocluct was
distillecl under vacuum ti~eleby gatl~erillg tlle fractioll
witll boiling point 117 to 118C (at 0.15 mmEIg), consisting
of 31.3 g of 3,3-dimetllyl-4,~,G-tribrolllo-7,7,7-trifluoro-
=.'9= ~37~3~
htptanoic acid etl~yl ester.
E k?melltll analysis:
Bromint?: calculated: 50.26%; ~ound: 4S.57%.
Exalllple ~
A solution of sodium ethylate (0.022 mols) in
ethanol (60 ml) was added to a solution Or 3,3-dimethyl-
~ ~ 6-tribromo-7 7 7-triCluoro-ht?ptatloic acicl etl~
es~cr (1.7 g) prepart-~d as ck?scribed ln ~;~alllpLe 3 in
etllanol (10 ml) under stirring wl~ile maintailling the
tcmperature bctween 19 and 23C. The rcsult;illg solution
was ~aintaintd at room tempcrature lor 3 llours
until the gas-chromatogl-apllic control showed the
complete disappearance Or tlle starting ester.
The solution was tllen concentr~ted poured
into water and ice and then extracted witll Cl-I2Cl2
(3 x 40 ml). The organic solution was then waslled
wi-th water until reaching a neutral pll and -thell dried
on anllydrous CaCl2.
Thc solvent was removed un(k?r vacu-lm tllelcby
obtainill~ 2.~ ~ o~ raw ~ro(luct whicl~ ~V.IS seplrat(tl
l)y columll chlomatograplly in ~ rracl;i(>l-s~ Tllrce ol'
t,llesc rract,iolls, allalysccl l~y g~ls-cllrolllato~ pl~y ~ ncl
idellt;; Ci.e-~cl ~ly ~as-cllromatograpl~y combinecl witl~ SS
spt-?c~ronlt?t~yJ sllc)wecl ~lle rOl lowill~ coml)t)sit:iolls:
= ;o= ~37a~39
ract iOIl I (0.3 g) = ethyl ester oI 2,2-climethyl-3-
(~-bromo-~-trirluoromethyl-~inyl)-
cyclopropanecarbo~ylic acid
(Compound (d), Table 3);
Frnction II (0.5g) = mixture consist.ing of about 55~0 oL
compound (d), n~out 20% o.f tlle
compound th~t Lorms fraction III
( compouncl ( :r ) ) and oL ~bout 25rj~
oL etllyl ester ol 2,2-dlmetllyl-3-
(B~R-dibromo-y,y,y-trilluoro-propyl)-
cyclopropane c~rboxylic acid
(compound (e), T~b].e 3);
FractiollIII (0.6g) = ethyl es-ter of 2,2-dimethyl-3-
( ~-t ri :Eluoro-metllyl-e tllyny l )-
cyclopropanecarbo~ylic acid
(compouncd (r), Table 3).
(tr,nns isomer)
_,.~__ .... . _ __ . . _. . .
31 ~%~3~
~xample 5
Preparation oL intermediate 3,3-dimetllyl-4,G,G-tricllloro-
7,7,7-trifluoro-heptanic acid ethyl ester.
7,8 g of ethyl ester of 3, 3-dimethyl-4-pentelloic acid
(0.05 mol),
18.75 g of l,1,1-trifluoro-triehloroethano ~0.1 mol),
0.25 g of cuprous chloride;
3. 5 ml O-e ethanolamine and
50 ml of tert-butylic alcollol
.l0 were loacled into a 100 ml flask, under nitrogell atmosphere,
The react:ion mi~ture was thell heated at reClux temperature
for 10 hours. After cooling, the tert-~utyllc alcohol
was removed by evaporation.
The residue, diluted with.50 ml of cdiethyle-ther, was
treated with diluted IICl until attai.ning an acid pl-l. The
etheric phase was then washed with water, neutrali~ed with
NaHC03, dried on anhydrous Na2S04 and the solvent was
evaporated to yield 17.2 g of an oil whieh, by distillation
under vacuum, yields 13.2 g O:e a Iractioll having a boiling
point of 105 to 110C at 0.6 mmllg, and consisting o~
3,3-climethyl-4,6,6-trichlolo-7,7,7-triIllloro heptanoic
acid etllyl esler (gas-ehromatograpllic titre = 93%).
~lemental analysis: chlorine
Caleulated: 30.96~o, Iound: 30.3G%
32 ~IL237~3
The I.R. and N.M.R. spectra o:~ this product were consistant
with -the indicated structure.
Example 6
Preparation Or ethyl es-ter o~ the (-)-~:is, Ir~ln~ 2,2-
dimethyl-3-(~-cllloro-,~-triLluoromethyl-vinyl)-cyclopropall('-
carbo~ylic ~cid (mix-ture o isomers) (compouncl (g),Table 3)
solution o:E 11 ~ of the intermecliate prepared according
to Example 5 (0.03 mols) in 10 ml oE ethanol was aclcled
to a solu-tion oi 0.06 mols o:E sodium ethylate in 30 ml
of absolute ethanol, at a temperature of -20C. The
reaction mixture was kept under stirring Ior 1 hour at
0C and, after allowing to rest overnight, stirrin~ was
resumed for 2 hours a-t 50 -to 60C.
~fter cooling and filtering oif from the sodiu~ chloride
that had Iormed (3.8g), the solution was poured into wa-ter
and ice and -then extracted with diethylether (3x30 ml).
The organic extract., was waslled with water and dried on an-
hydrous Na~S0~l, the solvent was evapora-ted to yield &.1 g
of an oil, whicll, on the basis oI the gas-cllrc)matogrclphi.c
analysis iollowed by the characterizatioll by mass-gas-
chromatograplly, proved to be constitllted pre(lc)minantl.y
of the isomers of compound (g) (about 83%~ ancl of a lesser
quantity (abollt 12%) of compound ( r) . The 1.~. spectrum
oI this mi~ture showed the presellce o.L` absorpti.olls
- - -
43~
characteristic Lor the double bond C=C (v = 1~50 cm 1),
o~ the triple bond C-C (~ = 2250 cm 1) and oI the C=0
esteric group (v = 1720 cm 1)
~xample 7
Preparation cf e-thyl ester o (-)-~is, trPnc-2,2-dimethyl-3-
-(~-trifluoromethyl-ethynyl)-cyc:Lopropanecarboxylic acid
(mixture of isomers).
8g of a suspensioll at 25% concentratioll O:r sO(Iium-llmide
in Degussa oil under 50 ml o~ anhydlous benzene, i.lltO a tvel.].
driecl round bo-ttomecl-flaslc of 250 ml hc)lcling capacit:y, equippecl
with a reIlux condenser and then, a-t 0 C under nitrogen
atmosphere, the following reac-tan-ts were added~
13.5 g of ethyl ester of 2,2-dime-thyl-3-(~-chloro-~-trifluoro-
methyl-vinyl)-cyclopropanecarboxylic acid (mixture of isomers),
5 ml o:E ter-butanol and
5 ml of anhydrous benzene.
The reaction mixture was maintained at 15 to 20C by cooling
with an external ice-water ba-th till. no mo.re he~t was evolved
(about 1 hour). The reaction mixture was then heated at
reflux t;empera-ture for 6 honrs and, after coo:ling ~.o room
temperature, it was poured in 100 ml. oC a 2N hydroge
chloride a~ueous solution. The orgallic phase w~s thell
separatecl, washed witll water till a neutral pll, driecl on
anhydrous Na2S04 and filtered. The organic solvent was
removed undel vacuum yielding 12.5 g of raw produc-t which was
34 ~ ~3~3~3
clistilled on a Vigreux column (10 cm higll), collecting the
fraction boiling at 93 to 99 C (35 mmllg) wllicll consisted
of the desirecl product, (Compound (h), Table 3).
By the comparison between the NMR data (see Table 3) of
compound (h) and of compound (f) it appears that the lat-ter
is the trans isomer.
~xample 8
Preparation Or ethyl ester O:r (~ ~S-2,2-tlimetllyl-3-
(~-trirluorometllyl(Z)villyl)-cyclopropallecarbc)~lic a.cid
(compound (i), Table 3) and oL the corresponclillg fnee acid.
(Compound (j), Table 3).
11~5 g of ethyl ester o:E 2,2-dimethyl-3-(~-trifluoromethyl-
-ethynyl)-cyc.lopropanecarboxilyc acicl (com~ound (1), Table 3),
200 ml of n. hexane and
~ g of palladium on calcium carbonate (Pd/CaC03)
poisoned by lead (prepared accordi.ng to Organi.c Synthesis,
Coll. Vol. V, 880, John Wiley ~ Son, 1973) were introduced
into a round bottomed flaslc of 500 ml holding capacity,
under nitrogell atmosphere.
The rlaslc was then connected -to a hyclrogenatioll apparatus and
the contents Or the flask were vigo.rously stirred ror some
hours till no more hyclrogen was absorbed.
The reaction mixture was then :riltered on Celitc?, ancl the
solvent was evaporatecl to yield 10~5 ~ ol raw prociuct that was
distilled at reduced l~ressure.
35 ` ~ ~374~9
The ~raction boiling at 88 C (16 mmHg~ was gathered and,
analy~.ed by I.R. and NMR spectroscopy proved to be compound (i)
(puri-ty:~ 90% by GLC, gas-liquid chroma-tography).
~ g oi` K0~l (85% conc) and 50 Ml of ethanol (95%) t~ere added
to 7 g of compound (i). The mixture was reilux heated for
4 hours.
~lost o~ the solvent was then evaporated and 50 ml of wa-ter
were added. lO g of an aqueous solution oi sulplluric acid
(l:l) were added to the resul-tlng m.ixture which was then
extracted with me~tllylene chloride. The organic plulse w~s
then clriecl 011 anhydrous Na2S0~, and :Eilterecl. ~y remov:in~
the solvent ullcler vacuum, 5.9 g of ~n oil wele obtainecl, whicl
crystallised ~rom n. pentane yielded compound (j) as a white
solid melting at 49 to 50C.
Example 9
Preparation o~ e-thyl ester of 2,2-dimethyl-3-(2,chloro-3,3,
_-trifluoro-propyl)-cyclopropanecarbo~ylic acicl.
Ethyl ester of 3,3-dimethyl-4-pentenoic acid (15.6 g, 0.1 mol),
l,l,l-trifluoro-chlorobromoetliane (59.2~,0.3 mol)
ethanolamine (3 ml) and Cu Cl (0.6 g) were introdu(,ed into
a Pyrex glass tube for reactions under pressure, under a
nitrogen at.mospllere.
Tl1~? ~IIISS tllbl? ~vas tllell ilc mc? Sl?~ ?~I ~n~l sl~ (ul to o~?t~
an homogeneous mixture, and thereafter it was introduced in
an autoclave containing water for about 2/3 of its volume.
The autoclave was closed and heated at 120 to 140C for 20 houi-s
.. ^ . -- - -- . .. . .... . .. , ~
3G ~3'7439
After cooling the glass tube vas opelled and the excess o~
l l l-tril].uoro-chlorobromoethane was dlstillecl under vacuum.
The residue was collected with dlethyl-etller washed
with an hydrogen chloride solution (2N) and then with wa-ter
till a neutral pH and filtered. The organic phase was
dried on anhydrous Na2S0~ and the solvellt was removed under
vacuum. The residue was distilled a-t reduced pressure
gathering -the iraction (20 ~) boiling at 70 to 75C (0.0~ mmllg)
consisting of ethyl ester of 3 3-dimethyl-4-bromo-~-cllloro-7
7 7-trifluoroi~eptanoic acid (nD =1.4~15 ~lemental ~nalysis
IR and NMR spectra consistent with tl~e assignecl structurej.
10 g Or this intermediate were dissol.ve(l in lO ml of
absolute ethanol and the resulting solution wns added at room
temperature to a solution of sodium ethylate prepaIed by
dissolving l.5g O:r sodium in 55 ml o~ absolute ethallol.
The l~eactiol~ mixture was then reflux heated for 1.5 l~ours
and the solvent was then evaporated ùnder vacuum and 100 ml
of water were aclcled to the residue.
The organic ma-terial. was extracted with diethyl etller
(3 ~ 75 ml).
The organic pllase was washecl Witil wat:er until a neutra:L
pll dried on anhydrouS Na2S0~ and -tlle solvent was evaporated
under vacuum. G.3 g of ethyl ester of 2 2-dimethyi-3-
(2-chloro-3 3 3--~ri~luoropropyl)-cyclopropLIlle carbo~ylic acid
were obtain~d as mixture oL cis trans-isomers (abou~
(compound (k) Table 3).
37 ~L~3~3~
E:xample 10
Preparation oI ethyl ester Or (-)~ , tr.n_-2 2-dimethyl-3-
-(R-Lr:irluorometllyl-E-vinyl)-cycloprop.)necarboxylic acid.
2.5 g oL C2ll50Na were dissolvecl at -15 C in 80 ml of dimethyl
formamide and a solution of 6~3 g of ethyl ester of (-)-cis
trans-2 2-dimethyl-3-(2-chloro-3 3 3-trifluoropropyl)-
cyclopropanecarboxylic acicl in 20 ml oC dimethylformamide
was added. The reaction mixture was slowly heated from -15 C
-~o 0C ovtr a period of 3 hours thtn 100 ml Or wll:er at 0~'C
were a~ded. The organic material was then extracted with
diethyl ether (3 x 100 ml). The organic solution was washed
with water until a neutral plE and clriecl with anhydlous CaC12
and the solvent was removed uncler vacuum~ 5 g of el:hyl
ester of (-)-c:is trans-2 2-dimethyl-3-(~-trifl~lorom~thyl-~-
-vinyl)-cyclopropanecarboxylic acid were ob-tained as~nixture
of c]s-trans isomers in about 1:1 ratio~ (Compound (1)
Table 3)~
The same reac-tion was carried out also at 0C for 15 hours~
~ product consisting of about 90% of the trans isomer lS
evidenced by the disa~pearance in the N~IE~ spectrum of the
signal at 1~85 ppm corresponding to the proton IIB Or the cis-
isomer was obtaintd.(Ste Tablc 3).
~37~3~
~ -
~o ~
o , o
r ,_ ^ O In - o
c~ ~ ~ C`J X I,e c~
U) co ~ ~ c~ . ~ 1:
r1 LD N ~ ~ ~ r
O
~) ~ O o ~ 1 0
~ u ~ ~ m c~
I I I
~ ~ + -~ + + ~ + C`
S~ ~ ;~ ~ ~; ~. C`l ~ ~ ~ C~
~ ~ ~ ~ ~ ~ ~ 2
o ~ C~ ~ Ln ~ c
a) ~ n N O CO 00
,D ~ ~ F~
rl ~ I n I I '`
h ~~1 ~ ~) Ln ~~
C) C~ ~:C ~ }~ ~ CO Lr) ~
~ . ~
Cq I C~ ~ I
a~ .
O
In In
"
~ oO O
I
~) a
5~ C~ ~) ~
r-l ~ r-1 \ / I \ / ¦
~ E / \ ~ ~, / \
~ ~4 ~ ~
E ' ~, a:l
CJ ()~
a~
~o
~o
o
E o ~ ,D
~0~ O . . ~ `
-
X ~J
3~4c39
_ I .
,~
o ,_ ~
+~ ~ o .~-,
iq LO 5 C~
~a h O ~C 8 h h
P ~ u ~ m m
h t~ C`~
~q h o O `-- `~ `_ ~ (_)
q~ ~ co m C9 ~ ~ +
cs c~
P ~ ~~ c~
a~ ~, ~ ^ ~' I ' ,r) t-
O ~ O
~ Ioll ~~ ~ c~ C`l C`~ C`l C~l
rq ~C~l ~ U~
~; x ~
h
~: '
~q
.~
O h X I~ .
d \ / ¦
r~ ~ ~ ~, ~
h IL~) m
~ ~)
o
~,q
o - - -
~o) ~
~ c)
- --
~i
~37~3~
, _
^ O n
,~
,_ u~ ~ ~ t,
ts~ ~ ~ O
~r4 t~ ~
m
O tY~ ~ + + +~ +: 2 ~N ~ t~
~ ~ ~ tS~ .1 ~ t~
u~ , t~ o t~
,~ ~ ~ ~ h t~ t,~
5~ N ~ h m E ,,
t~ t~, o ~ m ~: _~ ~ - E
Q ~ t`l I I t,
,~ t ) ~1 t;O ~ t O - t~) ~D E 5~
h ~ mts, ~ ~_tr~ 4~ --~ N
U~ h t~) t~ h `-- ,_, ~ ~, _
S 10 ~0 10~O ~ v~ 0 ~ C
G~ ~ ~ cd ~ C --' C~l ''
_~ ~1 1 1 1 r~ CL; N C~) t--
h ~ ~ t~ ~ C/~ I ~)
O t/~ C ) t;) 'I ~1 ,~ ; r~
C _ J ,tr~ t`')t~
h
S ~
n
m ~
O h O ~: o
C O
q~ 5: ¦ \ h
td t.~ ~ E~
t~ m
t~ ~ ~ \ ¢ '~
~ tr) 1~
q~ ~) ~ ct
o ~tr~ ~,
~ I -
E
cO~ :~
U~
43~3
f~
r-l ~ r~
~ u7 E ^
o ~ ~ ~m~
~, m c~ r~ ~ u
r~ ~ u l ¢ c~ E
P ~ m
~,~ ~ "~ G~
h h , _, ,, ~ ~o E ~ O
U~ S ~ oo
U ~
~ ~ _ oo I j Ir~~ . o o
h ~ 1 ~ ~ ~ ~ ¦ ~ . ~ . ~ 1 ~ co
Q ~
5~ _ .
S
~ Ir)
C~ ~ a~ ~ m
E O / ~ \ / ¦
r1 FLI ~ c~ ~ c )
h . C~ ~
b~ F~
O
E . _ _ _
C~ ~
U _ _
1~ J
3~3
'~ oC'
^ V N O
U~ ~ O
O ~ CS~
. ~ ~ V ~ 11
+ ~, "~
r, ^ :~ ~ m^ ;c t~ ~ .
m ¢ ~, ~ ~ m ~- ~ o
~ ~ ~ m m
,~ ~ ~ b~ m- ~ m ~ .,~
h ~o - ~ 11 ~) ` E V O
~I) td ~ ~ ` ^ ^ X ~ C~ 11
E m v ~ , v
(~ ~ ~ ~_, m ~ ~ ~ ~:
a~ ~ h ~ o
o c~ m ~ 9 ~ ,'
4~ ~
h _
h V
r h X
o ~o m j~\ ~ ~ /
t~ ~ / (ll t )
\ r1 '~
~)
o /\
U~ ~ ~
~ V _,
o
__
O . .
~ ~ r)
VO
;'li
3~
5,~, ~ _ _ ._
s ,~ a.
o ,~ m (~ ~ m ~¢ ~ t
Q ~ E E ^ ` ~ p, ~7 ~ ~ ~c ~I P~ x ~ t- v~
r l ~ ~ E E .~ ^ X ~ c`J
t~ ~ ~ ~ E ,~ a ~ P
O ~- I
a~ ~ _ ~ ~ ~¦
E D W
o ~ ~ ~ n ~ ~
a _ _
C~ ~,
E ~ ,~
C~ ~ .
_ .
b
3~
Notes to 'l'al)l e 3
~a) I\IS = ~lass-spt?ctroscopic data, only tl~e m,1in ions are~
reported .
(b) r~. I . = Re rraction Index.
c) NI~IR = 111 Nuclear klagnt-~tic Resonance spt?cll~oscopic data
~IR spectra were recorclecl using CDC13 as solvent
and 'r~ls as interna:l stand,lrcl.
s = singlt?t, d -- cloublt?t, t = I;rip:let, c~ = tlu,-rt:t?t,
m = multiple-t, J = couplin~ constalit.
cl) IR = In rra-Red spectroscopic data, only tlle more
s i gn i :r i ca t i ve b an ds are repor t ecl .
(e) 19F NMr~ spt~?ctra ~vere recolded using Cl)C13 as solvellt
and CFC13 as internal standard; d = doublet.
(I) tht? melting point has not been corr~ctetl.
~3~39
Example 11
Preparation of CF3-CFBr-CII2-CI-IBr-C(CIl3)2-CH(C02C21l5)2.
208 g oE CF3-CFBr2 (0.8 mols),
91.2 g of C~l2=cll-c(cH3)2-cH(co2Et)2 (0.4 mols) and
6 ml of diterbu-tyl peroxide were introduced into a
250 ml. Ilastelloy C autoclave fitted with a balance
rocker, under a ni-trogen atmosphere.
The autoclave was heated to 140C and maint,~ ed a~ this
tempera-ture :Eor 2 hours. ALter cooling, the contents ~Yere
discharged and the excess o CF3-CF13r2 was removecl by evapora-
-tion, a:Eter whicll the content of the autoclave was subjectecl
to molccular dis-tillation, gathel~ing the fractioll boiling
at 90C (10 3 mmllg) which consistecl Or 120 g of et.l-lyl-
(1,1-dimethyl-2,4-dibromo-4,5,5,5-t~trarluoro) penl;ye-malo-
nate.
n22 = 1.4513
I.R. analysis was cDnSiStent wi-th -the inclicated structure.
Elemelltal an.llysis: = foundc~al.culated
. C 34.9~0 3~.5%
11 ~1 . 2% ~ `o
F 15.4%15.6'~70
Br 31.g% 32. 870
- - -
L39
~6
Fxample 12
C~-13~ ~ C113
Prepara-tion of CF3-CFBr-C112-CH - Cl - C02C2H5 and o~
C02C2}15
C~13. ~ C113
CF3-CF=CH-C~I-C-C02C2115
C02C2}15
lU
~18.8 g (0.1 mols) o~ ethyl (1,1-dimetllyl-2,~1-di.bromo-~,
5,5,5-tetra-rluoro)-pel~tyl-malonate, prepared ns describecl
in ~xample 11, in 100 ml of anhydrous ethanol were added
dropwisc and uncler stirring to an ethanolic solution of
socdium ethylate, prepared ~rom 2.4 g of sodium and 100 ml
of anhydrous ethanol. ~fter the addition a sample was
taken from thc mixture which was gas-mass analyzecl and
the results inclicated that -the cyclization reaction had
nlreacly been fully completed to give coml)ouncl
C113 ~ C113
CF -CFBr-CH -CH-C ~ C2~2H5
C02C2~15
~3~7~39
47
~lass fragmentation:
(C14~ll9F~BrO4) : 406 (~I )
327 (M -Br)
361 (M -C2H50)
213 (M -C3F4Brll2)
315
314
185
167
43
~t this poin~ a further amount of sodium ethylate
in ethanol prepared as above was added and the
reaction mixture was ke~t under stirring at 40 C
for 5 hrs.
-15 A~ter neutralization with HCl, 1:1 and subsequent
filtration, the solution was concentrated -to a small
volume, additioned with 200 ml o:f water and -then ex-tractecl
with CIICl3 (2 x 150 ml). The chloroLormic extract
was then dried on CaC12 and -then evaporated to give
31.4 g of diethyl ester o~ 2~2-dimethyl-3-(~-lluoro-g-
tri:Eluoromethyl-vinyl)-cyclopropal~l,l-clicarboxylic acicl,
n22 = 1.4303
3 ~
CF3-CF=CH-C~ C-c02c2~l5
C02C2ll5
-
237~L391
Mass fragmentation: .
(C14~l18F4~) 326 (~I )
281 (M -C2H50)
253 (M+-C3H502)
225 (253-C2H~)
235
207
179
167
160
115
E,Yample 13
~<
Preparation of CF3-CF=CH-CH-CH-C02C2ll5
5 g of CF3-CF-CH-CH-C-C02C2H5, prepared as described in
C02C2~15
E,Yample 12, 1 g of NaCl, :L2 ml of dimethy].sulpllc).Yide and
0.6 ml of water were introducecl into a flask immersed in
an oil bath and fitted with a reflu,Y condenser under a
nitro~en atmospllere.
The reaction mixture was -then reflu,Y-heated for 9 hours at
165 to lG7QC.
After cooling the gas-chroma-tographic analysis indicated
`
3~
~9
.
.
that the compound had formed wi-th a conversion oC 75%
and with a cis/trans ratio on the ring of about 1:1.
Example 14
Prepar-ltion O:r CF3~CCl2-Cl~C~lCl~C(CI13)2~C~CO2C2Hs)2~
23 g of Cl~2=cH-c(cll3)2-cll(co2c2~5)2 ( '
82.5 g of CF3-cc13 (0.4 mol),
0.16 g o~ CuCl,
3.5 g of ethanolamine and
115 ml o:E terbutyl alcohol were introduced into a
~las-telloy-c autoclave with mechanical ~stirring, ullder
a nitrogen atmosphere.
The autoclave was heated at 100C for 2 hours and then at
110C for/~urther 7 hours.
After cooling, the reaction mixture was filtered and,
after removal of the excess o:E CF3CC13 by evaporation, the
solution was distilled at reduced pressure.
20g of a fraction having a boiling point o~ 105C (0.05
mm~lg) consisting o~ ethyl (l,l-climethyl-2,4,4-trichloro-
-5,5,5-trifluoro)-pentyl malonate were gathered.
I.R. (pure sample): 1720 and 1740 cm l(C=o); other
bands at:
1~160, 1362, ~300, 1255, 1227, 1205,
1175, 1040 cm 1
~L237~3~
5()
~lemental analysis: '
~ound Calculated
C(%) ~l.l ~0.~
H(%) 4.9 4.8
F(qo) 13.213.7
Cl(%) I ~S.l25.6
~xample 15
Preparation of the m=pheno~ybenzyl ester o.E (~ ,trans-
-2~2-climethyl-3-(B-fluoro-~-l;riLluc)rometllyl-vinyl)-cyclopro-
panecarboxylic acid and partial separat.ion oL the geometrical
isomers.
9.5 g o~ 2,2-dimethyl-3-(~-fluoro-~-trifluorome-thyl-
vinyl)-cyclopropanecarboxylic acid were converted -to -the
chloride of the acid by treatmen-t with 9.7 g of PC15 in 200
ml of CCl~ at 23 ta 2~C. By dis-tilla-tion under vacuum
6.2 g of -the chloride of the acid were gathered. (~lemental
analysis: found Cl = 14.29% calculated Cl = 1~.49~o)
2.2 g Or the chloricle Or the acict thus ohtaine(l were
esterified ~y treatment witll 2.2 ~ o.~ 3-pheno.~ybellzl alcol~ol
in lO0 ml of anl~ydrous benzene, con-tainillg 2 ml of pyridine,
at a te~mperature from 18 to 2~C.
Af-ter filtering of the pyrodinium sal-t, the solution
was washed wi,th 80 ml of an aqueous solution of IICl, then
witl~ water a(. O~C until attuillin~ ~ neutral pH.
r, 1 ~237439
A~ter dellydration, the solvent was evapornted under
vacuum to yield 4.1 ~ of raw 3-phenoxy-berlzyl ester o~ the
(-)-cis, trans-2,2-dimethyl-3-(B-fluoro-B-trifluoromethyl-
vinyl)-cyclopropanecarboxylic acid.
In order to achieve a partial separation oI the geometrical
isomers, the product was passed through a silica gel
chromatography column ~Filler: silica gel Kieselgel G (Type
60) prod. by ~lerk and analogous product by ~. Erba cocle
453332, in a weight ratio o.E 1:2, length Or column: 20 cm,
diameter of column: 2.4 cm; eluent: n-he~alle-bellzelle (2:1),
at room temperatllre~, gathering the ollowin~ fractions:
Fraction I : sample l-A (l g)
Fraction II : sample l-hl (0.6 g~
Fraction III : sample l-B (1.2 g).
On the basis of Nuclear ~lagnetic ~esonallce (N~IR)
analysis, sample l-A was found to consist predominantly
(at least 90%) of the isomer 3-phelloxyben~.yl-es-ter of
(-)-cis-2,2-dimethyl-3-(B-fiuoro,B--trifluoromethyl (E)vinyl)-
cyclopropanc-carboxylic acid.
Sample l-B was found to consis-t preclominantly (at least 80%)
of the isomer 3-phenoxybenzyl ester oI (-)-trans-2,2-
dimethyl-3-(g-f:l.uoro-~ rifluor()lnel,llyl(]I:)villyl)cycl.ol~Iol-)ane-
carboxylic acid.
Sample l-~1 was found to consist oL a mix~ule of the two
above indicated isomers in a cis:trans ratio of about 1:3.
'rhe characteristics of these samples are as follo~vs:
~37~3~
5"
l~i}~ ( ~, ppm) ( * )
H~ B 2 (m, ll~tllB)
~ COO-C112 ~ ~ 1 (dd, IIC)
F3C IC113 C~13 -CGH5 5 0~ (s~ C~12)
}IC 6.8-7.5 (m, aromatic protons)
J (Ilc, F -trans) = 33 Hz
Compound 1-A J (HC~ HA) = 9 llz
F C ~IC 1.7 (cl, Tl)
3 ~ 2.33 (dd, IIA)
HB 5.23 (cld, Ilc)
`00-C~12 ~ 1 lG (s, ~113)
C~13 3 o-C6115 5.05 (s, C~-2)
6.8-7.4 (m~ aromatic protons)
Coml)~und 1-B J(Hc, IIA) = 9 Elz
J(IIA, IIB) 5 Hz
J(llc, F trans) = 31 llz
(*) s = single-t; d = doublet; dd = doublet o~ doublet;
m = multipl~t; J = coupling constallt
r .,~
53 ~3743~
Example 16
Preparation of the2-methyl-5-benzyl-3-,ruryl-me-thyl ester
of the (-) - .(is, tr,~ns-2,2-dl.!llethyl-3-(~-~luoro-~-trirluoro-
methyl-vinyl)cyclopropaneearboxylic acicl and separatioll Or
the geometrical isomers.
Tlle eompoulld was obtained aeeordlng to a proeess similar
to that deseribed in Example 15 starti~g irom 2.2 g of
ehloride oI 2,2-dimethyl-3-(~-fluoro-B-tri~luoromethyl'-
vinyl)-cyelopropaneearboxylie aeid an(l from 2.3 g oC
2-metliyl-5-benY.yl-3-furyl-metllyl aleohol.
4.3 g of raw 2-methyl-5-benzyl-3-furyl-methyl ester
of (-)-GiS, trallS-2,2-dimethyl-3-(B~:rlUOrO,~B-tr.irl~lOl~Ometlly~
vinyl)-eyelopropalleearboxylic aeid wc,~re obtailled (N~ eonsist:ent
with the strueture).
I3y ehromatography on a silica gel column, under the
same eonditions deseribed in Example 15 the raw es-ter was
resolvecl into two geometrical isomers:
Fraction I : sample 2 A (0.7 g) (eis)
Fraetion II : sample 2 B (1.8 g) (tr.lns).
On tlle basis of the nuelear magnetie resonance analysis
(NMR) the sample 2 A was ~ouncl to consist preclominantly
(~ 90~o) Or tl~e isomet 2-me-thyl-5-bell~,yl.-3-Luryl-m~thyl est;er
Or (-)-cis-2,'2-cli.metllyl-3~ 'luoro4-trlrluoromel;lly~ ;)vill~.1 )
eyelopropanecmrbo~ylie aeid.
374~39
r~1
Sample 2 B was found to consist predominantly (~90%) of
the isomer 2-methyl-5-benzyl-3-furyl-methyl ester (-)-trans-
-2,2-dimethyl-3-(~-fluoro~ tri:Eluoromethyl(~;)vinyl)-cyclo-
propanecarboxylic acid.
The N~IR data of the samples 2A and 2B are as follows:
:~3~7~3~
- 55 -
NMR (~, ppm)
1.2 (s, geminal methyls)
~ U C113~ C112~ 1 . 5-2 (m, HA e HB)
CF3 ` C~l~ C112 l ~ 2 2 (s, CH3-C=C)
4.75 (s, OCH2)
5.8 (s, HD)
Compound 2-A 6.05 (dd, Hc)
7.1 (aromatic protons)
J(Hc, HA) = 8 Hz
J~C' F) = 33 Hz
1.15, 1.23 (s, geminal
methyls)
1.57 (d, H )
F 1~ B
~ c HB CII~O~C~12~,~ 2.27 (s, CH3-C=C)
3 HA' ~COO-CII ~ W 2-27 (dd, IIA)
CH3 CHX 2 11 3.8 (s, CH2)
4.75 (s, OCH2)
5.2 (dd, Hc)
5.76 (s, HD)
7.1 (aromatic protons)
Compound 2-B ( A' B) 5 Hz
J(HA, Hc) = 9 Hz
J(Hc, F) = 33 Hz
37~39
Example 17
Preparation Or ~-cyano-3-phenoxy-benzyl ester oI -the (-)-~i~.
tr~n.c:-2)2-dlmethyl-3-(~-Lluoro-~3-triLluorometllyl-vinyl)
-cyclopropanecarboxylic acid.
-
The above indicated compound was prepared by a process
analogous to that descrlbed in Example 15 starting from
2,2-dimethyl-3-(~3-fluoro-13--trifluorome1;1lyl-vinyl)-cyclo-
propanecarboxylic acid and ~-cyano-3-phenoxybenzyl alcohol.
A partial separation of the geometric isomers by
cllromatography On a silica ~el, as clescribed il~ E,YalnP1e 15
yieklt-~d the~ followin~ samples.
3-A: cis-isomer, puri-ty ~90% (NMR)
3-13: trans-isomer, purity ~90% (NM1l)
3-M: a mixture of isomers 3-A and 3-B in a ratio of about
3:5; refraction index N25'5 = l.5097.
The NMR data Or sample 3-A allCI 3-L3 are as fol]ows:
~?"
3L~37~3
57
C~ l~C N~ , ppm)
F / ~ /COO-Cll(CM) ~ 1.8-2.35 (m, 2H, ~ 3)
A ~IB o-C6i-15 5.9 (dd, lTI, Hc)
1.3 (s, 611, geminal methyl
Compoun~ 3-~ 6.22 (11-1, CH-CN)
6.8-7.5 (m, ~1-1, aromatic
protons)
J(ll~ C)
J(llc - F l,ralls) = 3l 11~,
2.32 (dd, 111, 11~)
~ ~ 1 7 (d, l~ B)
F A 1.22 (s, 3H, CH3)
/COO-CH(CN)~ O >
TIA ~ 1.32 (s, 3H, CH3)
O-C 11
6 5 6.25 (d, 111, CII-CN)
6.8-7.5 (m, ~11, aromati(~
Compo~1n~ 3-13 pl~olons)
J(11~ 3) = 511
J(~C-~ ~ral~
~;~37~3~
58
Example 18
Preparation of ~-cyano-3-phenoxy-benzyl ester of (-) -t.r~n.~-2,
2-dimethyl-3-trirluorometllyletllynyl-cyclopropallecarboxylic
acid
The above indicated compollnd was prepared by a process
analo~ous to that describecl in Exarnple 15 startin~ ~rom
2, 2-climethyl-3-triLluoromethylethynyl-cyclo~)ropanecarboxy l.ic
acicl alld c~-cyano-3-phenoxy-bellzyl alcohol. Tlle Ni~lR
data o~ the compound is as rOllOws:
~13C C~13
CF3-C-C ~ ' B fN
E~A COO-CH- ~
OC6115
N~IR (~, ppm) 1.83-2,2 (m, 211, IIA+IIB)
1 3 (s, 31-1, C~13)
1 35 (s, 311, C113 )
6 . 38 ( s, 111, CII-CN )
6. 8-7 . 7 (m, 911, arolll~l tic
protons)
59 ~3'743~
Example 19
Preparalion oL 3-phelloxy-bell%yl ester Oe tl~e (-)-~i~ 2,
2-dimcthyl-3-(~-cllloro-~-trif`luorometlly:L-vin~l)-cyclo~ropal.e-
carboxylic acid.
The above indicated compound was prepared by a process
analogous to that described in Example 15 starting from
2,2-dimetllyl-3-(~-chloro-~-trilluoromet,hyl-~ yl)-cyclopropalle-
carboxylic acid and 3-phenoxy-benzyl alcohol.
A partial separation ol` the gcometric~al isomers by
chromatography on silica gel, as described in E~ample 15
led to the following samples:
5-A : ci.s-is(:~mor, purity~ 9~! (NMR)
5-B : trans-isomer, purity ~90% (NMR)
5-M : a mi~tuIe of isomers 5-A and 5-B, in a r~tio of about
3:7; reLraction inde~ - nD6= 1.52GG.
The N~iR data of samples 5-~ and 5-B is as Lollows:
~3~
- 60 -
NMR t~,ppm)
c 1.6-2.7 (m, 2H, HA + HB)
I c113 c113 1.22 (s, 6H, geminal
-l \ / ~-~ methyls)
5 CF3-C(Cl) \ ~ ~coo-cll2~ o ~
;~ Y 5.03 (s, 2H, CH2)
o-c6ll5 6.7-7.5 (m, lOH, aromatic
protons + Hc)
Compound 5-A
2.4 (dd, lH, HA)
llc 1.8 (d, 1~1, HB)
cF3-c(cl)-~ ~3/C~13 5.82~ 2 duplets, lH, H~
6.1 ~ CiS -~ trans on t e
coo-c~l2 ~ ) double bond
-C6H5 1.20 (s, 3H, CH3)
1.30 (s, 3H, CH3)
5.08 (s, 2H, CH2)
Compound 5-B 6.8-7.5 (m, 9H, aromatics)
J(HA-HB) = 5Hz
J(HA-HC) = 9 H~
,~
r ''`b
13~
- 61 -
Example 20
Preparation of9~-cyano-3-phenoxy-benzyl ester oE the (-)-
cis,trans-2,2-dimethyl-3-(~-chloro-~-trifluoromethyl-vinyl)-
cyclopropanecarboxylic acid.
The above indicated compound was prepared by a
process analogous to that described in Example 15 star-ting
from 2,2-dimethyl-3-(~-chloro-~-trifluoromethyl-vinyl)-
cyclopropanecarboxylic acid and ~-cyano-3-phenoxy-benzyl
alcohol.
A partial separation of the geometrical isomers by
chromatography on silica gel, column as described in Example
15 led to the following samples:
6-A : cls-isomer, purity ~ 90% (NMR)
6-B : E, trans-isomer, purity > 90~ (NMR)
6-M :a mixture of isomers 6-A and 6-B, in a ratio of about
3:7; refraction index nD = 1.5256.
By an analogous preparation the mixture of isomers
(E+Z)-trans was isolated. (Compound 6C).
The NMR data of sample 6-A, 6-B and 6C are as
follows:
,,~
/
~3~7~3~
62
N~IR (c~, ppm)
C 1.95-2.45 (m, 211, HA+IIB)
I CII r Cll
I \ 3 / 3 1.3 (s, 611, geminal methyls)
CF3-C(Cl)==~
, COO-CH(CN) ~ C II 6 28~ ' ' '
A B G.7-7.G (m, lOII, arcmatic
protons -~ ~Ic)
Compouncl G-
~
Il .
3\ ~ 3 3 2.4. (d, d, lII, HA)
C=C \ X ~'IlB 1.8 (d, l}I, HB)
Cl ~ CIN 6.1 (d, lI~, IIc one single
HA COO-CH ~ isomer)
1.2-1.37 (s, s, 6H, geminaI
C6~l5 metIly1s)
6 37~ (s,s ll-I, CH-CN)
Cc)II~pc)~ G-~
6.8-7.6 (m, 9~, aroIllatic
protons)
J(~-HI3) = 5 ~z
J(HA-HC) 9Hz
~379c~3~
63
N~lR ~ .S, pplll)
c
l ~13C C113 H 1.2~1.4 (611, geminal methyls~
CF3-G(cl)=c~ B 1.76 (d, 111, IIB)
H I ~ 2.4 (dd, 11~, M~)
,~ C00-CI~O ~
0-C6115 6.08(~cl)
6 . 27 ( 111, CII-GN)
Comp o un cl 6 - C
6.8-7.55 ( m, ~)11, a romatic
pl`OtOllS )
~L~3~
6~
~xample 21
Preparation of 3-phenoxy-benzyl estc-~r oI (-)-c s,
I;ra.n~-2,2-climetllyl-3-(13-bromo-13-trifluorometllyl-vil~yl)
-cyclopropan(~carboxylic acid.
The above indica-ted compound was prepared following
the same procedure as that described in Example 15 and
starting from 2,2-dimethyl-3-(13-bromo-~-trifluoromet11yl-
vinyl)-cyclopropanecarboxylic acid and 3-ph~lloxy-bellzyl
alcollol,
A partial separation o~ the geometric isomers by
means o.~ chl^omatography on a silica gel column as clescribecl
i.n ~xclmple 15 yielcled the ~ollowin~ samples:
7-B = trans-.isomer, purity ~90% (N~IR),
7-M = mixture of cis-trans isomers in a ratio of about 1:1.2;
nD = 1,5326
~I NMR (~, ppm)
~1-1 C C~l 2.25 (dd, 111,HA)
F C-C(Br) = C 3 f 3 HB
3 ~ " 1.8 (d, lll,llB)
,' COO-C} ~ 5.l (s, ll~,l1c)
~-CG115 l.2 (s, 31l~cll3)
1.3 (s, 311,C113)
6.5 (d, 211,C112)
Compoull(l 7-B
~.8 - 7.55 (m,911,aromatic
J(~lA-1113) = 5 }1z
J(lIA~ ) = 9 H7~
~%3~3~
~xample 22
Prt!paratioll oC ~-cyano-3-p!lcno~y-ben~yl ester Or tl~e
s, tra.lls-2,2-dimetllyl-3-(B-bromo-~-tri:l`luoromethyl-
vinyl)-cyclo~ropanecarboxylic acid.
The above indicated compound was prepared by a process
analogous to that described in Example 15 starting from tlle
2,2-dimethyl-3(R bromo~ trifluorometl~yl-vinyl)-cvclo-
propallecarboYylic acid and ~-cyano-3-pl~e~no~y-benzyl alcol~ol.
A partial separation o:E tl~e geometrical isomel~s by
chromatography on silica gel~ as described in Example 15,
led to the i.solation of the ~ollowing samples:
8-~ : trans-isomer, purity?~90% (NM~)
8-M : Mi~ture o~ cls-trans isomers in a ratio of about 1:1.2;
refraction index - nD = 1.5310
CF3-C~Br) -' ~ 3 ` N~IR (~, PP!ll)
r-~ 2.2-2.6 (m, lll,H~)
,~' Coo-cll(cN) ~ O ~
~A ~ I.8 (d, lH,HB)
6 5 G.~ (2H, Ilc-~CH-CN)
1.2-1.33 (m, 6H
Com~ound 8-~ gemi.nal methy.l
G.9-7.6 (m, 9H
aromati.c proton~
( ~ HB) 5Iz
A IC) 9 llz
~237~3~
66
Example 23
_repartntion Or 3-phenoxyben7.yl ester Or (-)-~ralls-2~2-climethYl-
3-(~-trifluorometl~yl-Z-vinyl)cyc:lc)propa1lectlrboxylic acit1.
T1~e above indicated compound was prepared following
the same procedure as that described in Example 15 and startinK
from (-)trans-2,2-c1imet1lyl-3-(B-tri~luorometllyl-Z-vinyl)-
cyclopropanecarboxylic acid and 3-pheno~ybenzyl alcollol.
D \ /IIC N~ PIll)
C = C H3 ~ 113 11 2.45 (dd, ll-l, 11~)
CF3 ~ ~ 1.7 (d, 111, HB)
1i COOCII~ ~ 5.G5 (m,211, 1~ ~1ID)
1023 (d, 611, ~ellli1lal
O-CG115 , Me thyls )
5.1 (s, 211, C}12?
- G.8-7.6 (m, 9H, aro1natic
protons)
Compound 9-13 J (IlA-TlB) = 511z
67 ~23~7~39
Example 2~
PrepaIatioll of t~-cyano-3-phenoxybenzyl ester Or (-)-t~ s-
2,2-dimethyl-3-(~-trifluoromc~thyl-Z-vinyl)-cyclopropane-
carboxylic acicI.
The above indicated compound ~vas prepared following
the same proceclure as that described in Example 15 and
starting from (-)-_rans-2,2-dimethyl-3-(~--trirluorometIlyl-Z-
viny])-tyclopropallecarboxylic acicl antI tY-cy.ino-3-r)ll(!nt~xyl)c!nzyl-
alcoho 1 .
C N~R (~, ppm)
~ C 3 ~ 3 ,HB 2.45 (dd, lH,lI~)
- ~ ~ CN l.7 (d, lll, 1-1~)
A OO-CH- ~ 5.G5 (m, 211, Ilc IID)
H 1.23 (d, 611, geminal
C6 5 metIlyls)
~.3 (s, lll, CH-CN)
6.8-7.6 (m, 81I, aromatic
Compoullcd lO-B protons)
(II~ IIB) = 5 llz
68 ~3~7~L39
~ xample 25
Pre~aration of ~-cyano-3-pheno~y-beIl~,yl ester of t-)-trans-
2,2-dimethyl-3-(~-trifluoromethyl-E-vinyl)-cyclopropane-
carbo~ylic acid.
The above inclica-ted compound was prepared following the
same procedure as that described in ~ample 15 and starting
from (-+)-~r.lIls-2,2-dimetIlyl-3-(~-tri~luoromethyl-~ -vinyl)-
cyclopropanecarbo~ylic acid and ~-cyano-3-pheIlo~yb(?llzyl
al coho 1 .
~1
CF C
/ CII CI13 N~IR (~, ppm)
C = C ~ H 1.15-1.3 (6ll, ~emillal
~ B metIlyls)
D ,' \CN
A COO-C~ 75 (cl, lII, ~IB)
y 2.1 (dd, lII, IIA)
C6 5 5.9 (m, 2H, HC+HD)
6.3 (s, lH, CH-CN)
CompouncI ll-B 7.1 (In~ 9H, aroma-tic
nD = 1.5224 pro-tons)
( A B)
- J (~ 9 TI~
~ 23'743~
69
E:xample 26
Prt~parat;ion o r a-cyanO-3-phenOXyl~t?nzyl estel O e
(-),CL1 ~,t ~ ,2,2-climethyl-3-(2-chlo.ro-3,3,3-tri.:rluoropropyl)-
cyclol)ropallecc~rbt)xylic acid. (Componllcl 12).
A solu-tion o~ 3 g of (-)-cis,trans,2,2-dimetllyl-3-(2-chloro-
3,3,3-trifluoropropyl)-cyclopropanecarboxylic acid ch]oride
(obtained Irom the corresponclillg ethyl ester by hyclrolysis
and reaction with SOC12) in 50 ml anhydrous benzelle~, was
admixed to a solution o~ 2.9g o~ t~-cyano-3-phelloxy~enzYl
alcohol in 50 ml of anhyclrous benzene, 2 ml o-L pyricllne were
adclecl to tht-' resulting solution which was -tht-,~n kep-t at room
temperature~ Lor 24 hours.
The solution was then washed with water till a neutral
pl~, the org~nic phase was separated and dried, -thell the solvent
was evaporated under vacuum. 5.1 g of -the de~siretl product
as a yellow viscous oil were obtained (Refraction index
n D = 1.5125, elemental analysis and IR spectroscopic
data consistent with the assi~ned structurt,~).
~l3~ / C~13
C
/ \ CN
CF3-CIICl-C112-CII-CII-COO-CII- ~
O-CG115
.. .. . . . . . .
~23743~
~xample 27
I'repalation Or :3-phello:cyben~yl ester oî (-)-cis
2,2-dimethyl-3-(2-chloro 3,3,3-tri~luoropropyl)-
cyclo~?rop.~llecarboxylic acid (Compound 13).
Following the procedure described in example 26 and
by reacting 3 g of (-)-cls,trans-2,2-dimethyl~3-(2-cllloro-3,
3,3-triLluoropropyl~-cyclopropanecarboxylic acld chloride with
3-phenoxyben7.yl alcollol, 5 g of the clesired procluct were
obtained in iorm of a viscous colourless oil (Re:rraction
index n 23= 1.5160, IR spectroscopic data consistellt with the
assigned structure).
3 \ /
CF3-c~lcl-cll2-cH-c~l-coo-cH2- (~
O-C6115
~Compound 13)
The product was passed through a silica gel chroma1;ography
COlUmll USillg . mixture of nOhexane-diethyl ether (95 : 5~ as`
eluant.
Two samples were collectecl:
13-A, cis isomer, nD = 1.5169
13-B, trans isomer, n~ = 1.5171
r
-
71 ~X;~gL3~
Example 28
PrePIlI~atiOI1 Or C~-CYanO-3-PhenOXYbellZY1 eSter OE (-)-CiS)
t r~MS-2,2-dimethY1-3-(2~2-diI)rOmO-3 3 3-trir]~lOrOI)rO~~Y1)-
cyclopropanecarboxylic acid (compound 1~).
Adopting the procedure described in Example 26 and
by reacting 3 g of (-)-cis,traIls-2,2-dimethyl-3-(2,2-dibromo-
3,3~3-tri-fluoropropyl)-cyclopropanecarboxylic acid chloride
tv:ith -cyano-3-pIlenoxybenzy:lialcoIIol., ~I.5 g Or the desired
product were obtained in form of a viscous oil (Elemental
analysis and IR spec-troscopic data consistent ~vith the
assigned s-truc-ture)
\ /
C CN
O-C6115
(Compound 1~)
N~ , ppm)
lo2-207 (lO~I, protons o-f the acylic moie-ty)
G.3 (s, lII, CH-CN)
6.7-7.6 (m, 9II, aromatic proI;ons~
~237~39
72
~xample 29
Insecticide activity of the compounds of the invention,
The compounds o this i.nvention have been tested on
larva.e and on adults of the ~ollowing species of
phytophagouses, following the methods indicatecl hereunder
and the results are reported in Table ~.
~) 13iological activity on Maclosi.l:)llum euphor~iac? (aphicles)
SMall potato plants grown in pots were i.nfested
with adult: females of apilides and, a~ter a l`ew llours,
were then besprinkled with an aqueous clisl)c:rsi.oll O r l he
products under examination (see Table 4). 'I`he mortality
percentage was evaluated 24 hours after the treatment
(mortality of aphides on untreatecl plants = 0).
B) Bi.olo~ical activity on Pieris brassicae (lepydop-tera)
Cut-off cauliflower leaves were besprinkled with an
aqueous dispersion of the products ullder examina-tion
(see Table 4). ~fter drying, -the leaves were infested
with 5 days old larvae.
The mortality percentage of the larvae (mortality
on untreatecl leaves = 0) was determi.ned ~8 hours aIl.er
tlle treatmellt.
c) i.olo~ical activity on Le~tillot;ll~s.~ decelllline~lta
(Coleoptera)
Small pOt<ltO plants grown in pots were infested witl
. _ . _ ~ _ . . . . .. . .. _ . _ . . .. _ _ .. . ..
3~3
73
4 days old larvae, and the~n besprinkled with an
aqueous dispersion of the products under e~amination
(see Table 4). The mortali-ty percen-tage (mortality
untreated plants = 0) was determined 48 hours after
treatment.
D) Biological activity on ~lusca domestica (Dyptera).
4 days old adults were treated,by topical application by
a micro syringe, with an acetonic solution of the
products under examination (see Table 4). Tlle mortality
percentage (mortali-ty of insects treatecl only with
acetone = 0) was determined 24 hours aiter -treatment.
~) Biological ac-tivity on Culex piplens adults (Dyptera)
llectangular strips of ~Vhatman paper No. 1 were treated
uniformly with an acetonic solution of the proclucts
under e~Yamination (see Table 4).
~fter evaporation of the solvent, tl~e inside or
internal part of a perspex cyl:inder (moclel O~IS) was lined
with each -trea-ted paper and closed with a ne-t. 2-3
days olcl remales were thell introcluc~d illtO the cylinder.
~fter one hour irom the start oi` the contact, -the insec-ts
were transferred to an identical cylinder likewise lined
with untle~ated paper ancl i`ed with a sugary solution.
The mortality percentage (mortality of untreated
insects = 0) was determined arter 24 hours i`rom the
beginning of the treatment.
~3~3~1
7l
F) Biolo~ical activity on Blatta orientalis (Ortoptera)
The bottom and walls of glass crystalliæers (cylinders)
weIe treated unirormly with an acetonic solution oI the
products under examinatioll (see Table 4).
~fter evaportation of the solvent 80-100 days old
neanides were introduced into each crystallizer, after
~vhich ~he crystalli7.ers were closecl with a mc-~l;al net
cover. 24 hours after the starting of the treatment
the insects were transferred inl;o similar, ulltreatecl
crystalli~,ers and were properly no~lrislle(l.
The mortality percenta~e (mortality of ulltreated insects
= O) was determined 48 hours after the start of the
treatment.
G) Biological activity of aclults of 'l'etranychus urticae (~cari
Discoicls of leaves of bean plants were infested with acarus
adults and successively besprinkled with an aclueous
dispersion of the products under examination (see Table ~),
The mortality percentage was determined 24 hours after the
treatmellt (mortality of acari on untreatecl discoids - O).
_ 75 _ ~ ~23'7~
. - _ ~ ,
~n~ ~ o o ~D O
~C ~ a~ c~7 ~D
. h j O _
0 ~.g ~ . . o o .
t~ _ __
. 'L~~ g g g ~ O 0 O g
O ~ _ ~ ~ .-1 ~ ~ ~ ~
a~ ~ _ ,
)NE ~ o ~ o ~ o ~ o
m ~ ~ o o o O O O O o
a) .
tJ _ ~ c1~0 ~ 1-- o o
t) ~,~ ~_ ~ ~ ~ ~
11 t~ P. ,~3 E o o o o
~ _
_ o o o ~ o o o o
" ~ ~o o o o ~ o C~ o
~1 ~ ~ ~1 ~ ~ ~1 ~
o ~a~. ~ ~ u~ _~ In ~ In ~1
~ ~ o ~ o o o o o o o o
U~ . ~ ~ o o o o o o o o
ra .
~r ~ ~ .~ O~o ~ ~o ~o L~
~1 S~ ~
~ I .o~ ~o o 'o~ ,~
x a. o o\o . . . .
c,~, a) ~ ra -
_ _
,~ ~ _ ,g~ ,~ ~ ,~ ,~ ~ ,,
. ~ m o oP O g o ~o o go ,~,
o O o o o O O o
r~ . . .
.,~ E ~o o o o o o o
~ ~ ~ ^ o o o o o o o
la .~ ~c~p ~,~ ~, ~,~ ~
n In In ~n In
_ ~ o ~ o ~ o ~ o
~ oo ~ o o o o o o o o
~ 9ra I
.
r~
o ~ ~ m ~
- 76 ~ L3g
_
_ U~ ~ I~ o o ,~ o o 'o I
o ~ 8 ~ ~ ~ ~ ~ ~r ~ I
~ ~ _ _
~ h ~ o , o , ,, , ,~
V . .,~. _ ............... _ _
C O ~o~ o o o o o
~ __ E o , , , 1~
~ ~ O'~ ~u~ ,~ o o ~r ,~ o
C~ ~ ~D N_
O _ U~ t ~ t~l t~l t~ ~ ~1 N
C4 '_ O O O O O O O
h u_ ~ o o o c o ,~ o
E. ~~ c o,~ , o o o o o
U~ ~o o o o o o o o o
ra _ _ ,
V Q~ ~~ _ U/ r~ o o o r~ r~
~ ~' ~ a)~ o o o o o o o
;~} _ ~a ~ o o o o o o o
~ 1~ n o o o o~ o o oo
m ~ ~ uO~ o
I o O o o o o o oo
V o ô oO o o _ o oo
- ., ~ ~ ~ ,~ ' ,~ ,~ ,~ ,~ o ,~
~ ~ o dP r n o~ o o o ~ o o
a) O O O o o o o o o
'CJ . .. _ _
.~ ~ ~
u ~ m ~ m :~: m o
C ~ ~ _ r~ rl r ~ ,1
- 7 7 - ~ %3~3
,_
~ ~,_ ~ ~ I
~ ~ V ~ ~ ,~ l
~ ~ o E o o
U
1~ 1~ ~o\3 O 0~
u, :~ a c O O O
~ ~ 1~ ~t~
~ X ~ U~ ^ ~, ~
~ .~ ~ Vôp
v ~ V ~ 6 o l
~ ~ ~d~ ~ oO~O
C o~ ~^ . ~o oo
~ ~ ~o~ o oo
rd
u ~ ~u~ ~ ~ ~
H ~4 ~ ~ _ O
.~
37~39
~xample 30
Acute toxicity on ra-ts by oral administering
/~nimal under test: albino mouse; ~Vistar brallcll, 50% males
and 5070 fenlales.
The animals, after a stalling period, were kept -fasting
from 6 hours before to 2 hours after the trea-tment and were
successively kept under observation ~or 1~ days, during wllicl
they were fed with calibratecl foclder in pellets and uater
libitum Tlle treatment was carried out by intro(lu(illg inlo
the stomach of the animals established quantities Or the
product through a gastrie probe eonneeted to a precision
syringe.
During the wl~ole periocl o~ observa-tion the mortality
and all possible symp-toms of intoxica-tion were recorcled.
Compound l-B was tested on rats according to the above
speeified methodology, in a dose o~ 200 mg o~ ac-tive substance/
kg of live weight, witllout observing any mortality of the
-tes-t animals after -the test.
F.xample 31
Activity all~ action persistenc~ test (?11 acari ill tll(' Op('
Iielcl~
The -test was conclucted in the open ~ield in
order to test the activity and persistance o~ aetion of a numbe
of representative eompounds agains-t acari ~Tetrallycllus urticae~
resisting -tl~e commonly used insecticides.
79 ~;~37~3~
Tlle compounds were applied in the form of a dispersion
in water and acetone with the~ additlon of a wetting agent
("Fitoril" ~lontedison in a 0,05% concentration~ sprayillg
them uniformly on the cultiva-tion up -to the limit o~ dripping.
(Concentration oL the active principle = 0.03%).
Data were recorded at time in-tervals from the start of
-the treatment, by couIlting the number of adult acnri presellt
on suitably salllpled leaves.
It is well Icnown that under the above speciEied conclitions
all the pyre-throids lis-ted in Table 1~ with -the e~ception of
Permethrin, Cypermethrin and Decamethrin, untlergo a ~ast clecay
becoming totnlly inactive after a very short petiocl c~f -time.
From our tests i-t revealed that Permetllrin ancI
Cypermethrin become -totally inac-tive arter 1~1 days whe~reas
the compounds of the present invention still e~hibitecl high
activity after tllt-~ same period of time.
