METHODE DE SEPARATION DES ACIDES VINYLCYCLOPROPANECARBOXYLIQUES STEREOISOMERES

PROCESS FOR THE SEPARATION OF STEREOISOMERIC VINYLCYCLOPROPANECARBOXYLIC ACIDS

Abrégé anglais

Abstract of the Disclosure
A process for the separation of the cis- and trans-stereoisomers
of a mixture of cis- and trans-substituted vinylcyclopropanecarboxylic acids
of the formula
<IMG>
in which
R each independently is alkyl with 1 to 4 carbon atoms or halogen,
comprising subjecting the mixture to distillation to obtain a distillate
enriched in cis-isomer and a residue, dissolving the residue in a solvent,
and selectively crystallizing at least one of the stereoisomers from the sol-
vent. Crystallization of the distillation residue results in first crystall-
izing that one of the isomers which is present in larger amount.

Revendications

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for the separation of the stereoisomers of a substituted
vinylcyclopropanecarboxylic acid of the general formula
<IMG> (I)
in which R represents halogen, the R's being identical or different, the
substituents on the cyclopropane ring are in the cis-position or trans-
position to one another and the molecules can also exist in the optically
active form, which comprises subjecting the free acid to fractional distil-
lation under reduced pressure and purifying the individual fractions by re-
crystallisation.
2. A process according to claim 1, in which the distillation is effected
at a temperature between 100° and 200°C and under a pressure between 10-3 and
10 mm Hg.
3. A process according to claim 2, in which the distillation is effected
at a temperature between 120° and 160°C and under a pressure between 10-2 and
2 mm Hg.
4. A process according to claim 1, 2 or 3, in which the recrystallisation
is effected from an alkane with up to 8 carbon atoms, petroleum ether,
cyclohexane, tetrachloromethane, chlorofluoroethane, an aqueous alcohol, a
ketone or an ether.
5. A process according to claim 1, 2 or 3, in which each R is chlorine
or bromine.
6. A process according to claim 1, 2 or 3, in which the distillation is
effected in a packed column or a bubble tray column.
7. A process according to claim 1, 2 or 3, which is carried out contin-
uously.

Description

34 ~3
The present invention relates to an unobvious process for the sep-
aration of known substituted vinylcyclopropanecarboxylic acids into their
stereoisomers.
Cyclopropanecarboxylic acids are intermediates for insecticides
(pyrethroides). Separation is necessary because activity of the end products
depends on their stereochemistry as well as on their structure.
It has already been disclosed that mixtures of stereoisomeric cis-
substituted and trans-substituted cyclopropanecarboxylic acids can be sep-
arated by fractional crystallisation. ~Coll. Czech. Chem. Commun. 24, 2230
(1959); Pestic. Sci. 1971, 245; Pestic. Sci. 1974, 791 and DOS (German Pub-
lished Specification) 2,439,177). However, that process is troublesome and
wasteful. The process is not suitable for isolating relatively large amounts
of pure trans-isomers or cis-isomers.
The present invention now provides a process for the separation of
the stereoisomers of a substituted vinylcyclopropanecarboxylic acid of the
general formula CH3 3 ~
R ~ COOH (I),
in which R represents halogen, the R's being identical or different, the
substituents OJI the cyclopropane ring are in the cis-position or trans-posit-
ion to one another and the molecules can also exist in the optically activeform, which comprises subjecting the free acid to fractional distillation
under reduced pressure and purifying the individual fractions by recrystal-
lisation.
It is to be described as decidedly surprising that the cis-isomer
acid can be successfully separated from the trans-isomer acid by the process
according to the invention, wherein the cis-acid first passes over in a con-
centrated form as the
".. ~,
~ ~ -2- ~

443
constituent with the lower boiling point, and can be easily purified in the
crystallisation as the more sparingly soluble compound, for it is emphasized
again and again in the literature references cited above that the cis-acid
is the more readily soluble isomer.
Moreover, it is surprising that it is possible to separate the cis/
trans-isomers in a simple manner by distillation, for it was known from the
state of the art that substituted vinylcyclopropanecarboxylic acids are un-
stable towards heat.
The process according to the invention has a number of advantages.
Thus, the cis-isomers, which are sometimes present in a cis/trans mixture
in only minor amounts, can be separated off from the major proportion, con-
sisting of the other isomers, and this can be used both for purification and
for concentration purposes. Furthermore, the process according to the in-
vention is also suitable for isolating relatively large amounts of the partic-
ular isomers and can be carried out continuously.
The formula (I) provides a general definition of the substituted
vinylcyclopropanecarboxylic acids which can be separated into their isomers
by the process according to the invention. Each R preferably represents
methyl, chlorine or bromine.
Examples of the compounds which can be separated into the stereo-
isomers by the process according to the invention are: 2-~2,2-dichlorovinyl)-
3,3-dimethyl-cyclopropanecarboxylic acid and 2-(2,2-dibromovinyl)-3,3-di-
methyl-cyclopropanecarboxylic acid.
The isomer mixtures of substituted vinylcyclopropane-

4~3
cæboxylic acids of the general formula (I), which are used as the stæting
material, are known (Coll. Czech. Chem. Commun. 24,2230 (1959); DOS (German
Published Specification) 2,615,159; J. Arg. Chem. Food Chem. 21,767 (1973);
British Patent 1,446,304; Pestic. Sci. 1971, 245; Pestic Sci. 1974, 537;
British Patent 1,413,491; J. Chem. Soc. 1945, 285; DOS (German Published
Specification) 2,432,951; J. Org. Chem. 17,381 ~1952) and DOS (German
Published Specifi Qtion) 2,439,177).
In carrying out the purification prooess according to the invention,
the isomer mixture is first distilled, according to customary practioe, in
vacuo over a column with good sep æ ation in order to obtain a first running
which contains a high proportion of cis-isomer. This first r~nning is taken
up in a solvent. On cooling, the excess pure cis-isomer crystallises out of
this solution, whilst the trans constituents remain in solution together with
an equimolæ amount of cis-isomer. mis result is contræy to the teaching
from German Offenlegungsschrift (German Published Specification) 2,439,177,
in which it is maintained that the cis-compound is the more readily soluble
compound in a solvent, such as hexane, and that the trans-oompound is the
mare sp æingly soluble compound. According to our results, that acid which
is present in exoess first crystallises out of the solution and in each case
a 1 : 1 mixture of d s- and trans-isomers then remains in solution as the
more readily soluble constituent.
The cis-acid which has crystallised out in the manner described is
æparated off. The filtrate is concentrated and recycled again to the dis-
tillation, only a first running which is greatly enriched by cis-iscmers
again being distilled off. The pure trans-acid is obtainable from the
residue of the partially carried out distillation by recrystallising once.

4~3
According to a particular embodiment, the entire process
can he carried out continuously by a procedure in which a solvent
i5 added to the first runnings of the vacuum distillation, which
are taken off barometrically, if appropriate, the cis-isomer is
separated off in a cooling zone and the mother liquor is concen-
trated, new solvents being fed to the distillate and the residue
being fed into the distillation again. This cycle is repeated
until the cis-isomer has been completely separated off. The
trans-isomer is then distilled over for purification. Complete
separation of the isomers without losses can also be achieved on
a large scale in this manner.
The distillation is carried out a~ temperatures between
100 and 200C, preferably between 120 and 160C.
The distillation is carried out under a pressure between
10 3 mm Hg and 10 mm Hg, preferably between 10 2 and 2 mm Hg. The
distillation should be carried out with such a speed that the sub-
stituted vinylcyclopropanecarboxylic acids to be distilled are not
subjected to the sump temperature for longer than 10 to 15 hours,
preferably 12 to 13 hours. Columns with good separation, such as
rotating strip columns, bubble tray columns, Vigreux columns and
packed columns, preferably packed columns or bubble tray columns,
are used for the distillation.
Suitable solvents for recrystallising the distillate
are non-polar solvents, such as alkanes with up to 8 carbon
atoms; petroleum ether or cyclohexane; halogenoalkanes, such as
tetrachloromethaneor chlorofluoroethane;and also highly polar
solvents, such as aqueous alcohol, ketones or ethers.
The stereoisomeric substituted vinylcyclopropanecarboxylic
acids of the ~ormula (I) obtained by the process according to the in-
vention are used for the preparation of highly active insecticides.
The examples which follow illustrate the process according

34'~3
to the invention without indicating a limitation with regard to the extent of
its applicability:
Example 1
1 mol of the isomer mixture of 2-(2,2-dichlorovinyl)-3,3-dimethyl-
cyclopropanecarboxylic acid (cis/trans ratio = 40/60) was slowly fractionated
over a 2 m packed column, which was packed with glass Raschig rings, under a
pressure of 0.5 mm ~g. me constituents passing over at 142C rapidly
solidified and proved to be pure cis-acid. me fraction from 143 to 152C
also gave, after taking up in petroleum ether and crystallising at o&, pure
cis-isomer, which was filtered off. The concentrated mokher liquor was fed
into the distillation again. The entire cis proportion could thus be
separated off in a simple manner. After recrystallisation from petrole~m
ether, the pure trans-acid was obtained, as was determined with the aid of
the NMR spectra, from the distillation residue of the distillation, which had
been incompletely carried out.
Example 2
1 mol of the isomer mixture of 2-(2,2-dibromovinyl)-3,3-dimethyl-
cycloprcpanecarboxylic acid (cis/trans ratio = 15/85) is distilled under 10 2
mm Hg as described above. me fraction up to 150 & was recrystallised fr~m
petroleum ether as above to isolate the cis-acid.