Note: Descriptions are shown in the official language in which they were submitted.
~z~
The present inYention relates to a process for
the preparation of substantially pure pyrazole compounds
of the general formula
R3
~C~2
where O
` R is hydrogen, halogen, alkyl of up to S carbon
atoms, alkoxy of up to 3 carbon atoms, perhaloalkyl of up
to 3 carbon atoms or alkoxyalkyl of up to S carbon atoms,
Rl is hygrogen, halogen, alkyl of up to 5 carbon
àtoms, alkoxy of up to 3 carbon atoms, perhaloalkyl of up
to 3 carbon atoms or alkoxyalkyl of up to 5 carbon atoms,
R is hydrogen, halogen, alkyl of up to 5 carbon
atoms, alkoxy of up to 3 carbon atoms, perhaloalkyl of up
to 3 carbon atoms or alkoxyalkyl of up to 5 carbon atoms,
or R together with R is an ortho-linked alkylene chain of
up to 6 carbon atoms which is unsubstituted or substituted
by alkyl of up to 4 carbon atoms,
X is chlorine or bromine, and
R3 and R4 are identical or different and each is
hydrogen, alkyl, alkoxy, alkylthio, carbalkoxy or perfluoroalkyl,
in each case of up to 4 carbon atoms, or halogen, phenyl,
cyano or carboxyl,from the corresponding crude products, such
. .
as are
.
.. . . . .. . _ _ _ _ .
x qr
- 2 - o.Z. 0050/03351~
obtained. for example, from the industrial manufacture of
the pyrazole compounds or suGh as are present in impure
production batches of the pyrazole com?ounds, if the pro-
duction process has not followed its proper course. or
such as are obtained from a simplified process for the
preparation of the pyrazole compounds without purifica-
tion of the intermediate products, by treating the crude
products with an aqueous solution of a strong acid and
isolating the pure products from the aqueous solution.
The preparation of the above pyrazole compounds
is disclosed in German Laid-Open Applicat70ns DOS
2,648.008 and DOS 2.704.281. According to the pro-
cesses described there, the products are obtained as a
; solution or suspension in an organic solvent. eg. chloro-
form, toluene. petroleum ether. ethyl acetate or gasoline,
and must then be separated from this solvent. for example
by evaporation of the solvent. or by filtration.
These methods are very easy to operate in a laboratory and
also give very pure products.
If attempts are made to scale up these laborato~y
processes. for example to pilot-plant or production
operation' unexpected di~ficulties arise, of which some
are mentioned below:
If the product is in the form of an organic solu-
tion, the solvent must be evaporated off, if necessary
under reduced pressure. Hereupon, the product prefer-
entially crystallizes on the walls of the evaporation
vessel used, for example a kettle. and cakes firmly onto
these walls. It is known that it is extremely diffi-
,
2~ ~ ~ 3
_ 3 _~ o.z. oOS0/03351~
cult to remove a solid product, in particular a caked-on
product, from a reaction kettle having the conventional
small inlet and outlet nozzles. In fact, the appara-
tus must, for this purpose, be dismantled by expert
staff, entailing considerable time and substantial labor.
The expert personnel, namely fitters, required for the
purpose are furthermore normally not trained in the handl-
ing of chemicals and in the observance of chemical safety
regulations and could suffer injury through inhalation
lo of. or contact with, adhering residual solvent. or pro-
duct dust.
If it proves possible to obtain the product as a
suspension in an organic solvent, the latter must be
removed by flltration. Depending on the toxicity and
explosive character of the solvent, the filtration mus~
be carried out with more or less troublesome safety
measures. which again entail considerable expenditure of
time, and substantial costs. Furthermore, in many cases
a substantial amount of dissolved product is lost with
20 the filtrate. ~ -
It is possiblej for example. ~o precipitate the
product, dissolved in an organic solvent, by adding a
second solvent which is miscible with the first but in
which the product is sparingly soluble. However, the
amount of produc~ precipitated, and its purity. dépends
on the amount of the precipitant solvent.
The products can also be isolated in the conven-
tional manner by precipitating them in the form of their
salts from their solution in an anhydrous solvent, in
.
~......................... . . . ..
0~3
- 4 - O.Z. 0050/033518
which the salts are insoluble, by adding excess anhydrous
acid. for example by introducing gaseous hydrogen chlor- -
ide. However, even then the organic solvent contain-
ing the acid must be removed from the salt by filtration
with due attention to all safe-ty regulations, and addi-
-tional difficulties are that the excess acid can adhere
to the product and pollute the environment and exert a
corrosive action. and that it is also present in the
filtrate and presents difficulties on reprocessing or
o destroying the solvent. Frequently. the addition of
concentrated anhydrous acids, eg. hydrogen chloride.
sul~uric acid and nitric acid, to organic solvents also
produces undesirable or even dangerous side-reactions.
Using the conventional precipitation of the products by
means of an acid. there is the further disadvantage that
not only the desired product itself, but all by-producls
capable of conversion to salts are precipitated.
A further factor to be borne in mind is that the products
precipitated as salts must be reconverted to the corres-
ponding free bases in an additional process step.This is absolutely essential since the salts hydrolyze in
a moist environment, for example on exposure to the
atmosphere. and in doing so liberate pungent and corrosive
acid.
A ~urther obstacle to scaling up the conventional
and inherently very satisfactory laboratory process to
pilot-plant or production operation is that ~or operation
on a larger scale the available reagents and solvents are
frequently not as pure as in the laboratory, and that the
~.~2~()43
personnel is not as well trained ln chemical matters as is
laboratory personnel. As a result, the products obtained
are in most cases con~aminated with by-products. The removal
of these by-products is almost always very involved and only
rarely succeeds completely. For example, some of the known
products can be recrystallized from cyclohexane. However,
in doing so the commonest impuritles, namely compounds of
the general formula
;. ~,~ /H
R2~ --C-CH2X
Rl o
- where R, Rl, R2 and X have the above meanings, can only be
removed incompletely from the pyrazole compounds, since these
impuri~ies are also sparingly soluble in cold cyclohexane.
Furthermore, substantial amounts of the pyrazole compounds
are lost during recrystallization. Of course, on isolating
the recrystallized subs~ances from organic solvents on a
large scale, the problems described above a~ain arise.
It is an object of the present invention to provide
a process by means of which it is possible to isolate the
pyrazole compound in a simple manner and in high purity even
from very large pilot-plant and production batchesl and by
means of which even contaminated batches of the pyrazole
compound can easily be purified.
The pyrazole compounds are aminals, cince they
contain 2 nitrogen atoms bonded to one methylene group.
It has long been known to those skilled in the art that
.
- 6 - o.Z~ 0050/033518
an aminal can be cleaved with an aqueous solution of a
strong acid to give a carbonyl compound and two nitrogen
compounds (P.A.S. Smith, Open-Chain Nitrogen Compounds,
W.A. Benjamin, Inc., New York. Amsterdam 1965. Vol. I.
page 322).
It has been found, surprisingly. that though the
pyrazole compounds possess aminal structures they are
stable to strong aqueous acids and can even be dissolved
undecomposed, in the form of their salts, in concentrated
lo aqueous acids. Since. however. the pyrazole compounds
are only very weak bases. they remain undissolved in
dilute aqueous acids.
Accordingly, we have found that the above object
is achieved, according to the in~ention, by a process
wherein the crude products are treated with concentrated
aqueous solutions of strong acids~ thereafter the aqueous
solution is separated off and diluted with water, and the
pure product which hereupon precipitates is separated
from the aqueous fluid. For example. the solution of
20 the crude product in an organic solvent which is immis- -
cible or only slightly miscible with water is intimately
mixed with a concentrated aqueous solution of a strong
acid and the aqueous phase is separated off and then
diluted with water, whereupon the product precipitates in
a pure form and can easily be filtered off from the
aqueous suspension. and be dried.
However it is also possible, for example, intim-
ately to mix crystalline crude product or contaminated
crude product in a solid finely divided form with a con-
, _ . . . ... , _ _ _
_ 7 ~ ~ o.z. oO~o/033518centrated aqueous acid, filter the mixture, dilute the
filtrate with water and filter off the pure product which
hereupon precipitates. Drying the moist pure products
presents no technical problems or safety problems.
If the crude product is in the form of a solution
in an organic solvent in which some of the impurities are
only sparingly soluble, for example a solution in a
straight-chain or cyclic paraffin hydrocarbon, eg.
hexane, heptane, octane, cyclohexane, petroleum ether.
naphtha, gasoline and the like. it is advisable to filter
the mixture ~Jith the aqueous acid before ef~ecting the
phase separation. in order to be able to achieve a sharp
phase separation. Suitable solvents for the crude
product are, in addition to those already mentioned, all
solvents which are immiscible or only very slightly
miscible with aqueous acids~ for example aromatic hydro-
carbons, eg. benzene, toluene, xylene~ chlorobenzene,
dichlorobenzene, chlorotoluene and higher alkylben~enes;
aliphatic chlorohydrocarbons, eg. methylene chloride,
chloroform. dichloroethane and carbon tetrachloride,
and ethers, eg. diethyl ether. diisopropyl ether and the
like. It is also possible to use esters. amides.
nitriles and similar compounds as solvents. provided these
are sufficiently stable to aqueous acids or provided the
process is carried out sufficiently rapidly to prevent
substantial hydrolysis of the solvent. Basic solvents.
which form salts with the acids used, must not be used.
Suitable acids are essentially all strong inorganic
acids, such as, for example, hydrochloric acid, hydrobromic
'
~.~L2~
- 8 - O.Z. oOsO/O33518
acid. perchloric acld, sulfuric acid. nitric acid and
phosphoric acidO The concentrated acid solutions
employed should contain from lO to 70% by weight, especi-
ally from 20 to 65% by weigh-t. of water; for example,
hydrochloric acid o~ from 32 to 38% strength or sulfuric
acid of from 40 to 80% strength may be used. Highly
concentrated acids. for example 96% strength sulfuric
acid or nitric acid of more than 50% strength, are rather
unsuitable because they have an oxidizing action.
The amount of acid used must be selected so that
all basic substances which are dissolved in the organic
solvent or are present in the solid residue are converted
to their salts. This requires at least an amount of
acid equivalent to the theoretically calculated amount of
the pyrazole compound. However, it is advisable to
use from lO to l.00~/~ excess of acid. The use of a
2-fold to 5-fold molar excess has proved particularly
advantageous. If in spite of using such an excess a
proportion of the desired product nevertheless remains
in the organic solvent or in the solid residue. the crude
product can of course also be treated a second time, or
several more times t with concentrated aqueous acid.
Of course. the pyrazole compounds can also be extracted
continuously with acid from their solution or from a
solid residue in which they are ~resent.
The temperature does not play a maJor role in the
extraction, apart from the fact that if it is too high
decomposition and poor phase separation may occur or an
excessive amount of non-polar by-products may pass into
. _ . , . , . . . . , _
,
. . ~ ' ~ .
_ g _ o.z~ 0050/03351&
the aqueous phase, whilst if the -temperature is too 1GW~
the product, the solvent and the water may pre~ent diffi-
culties through crystallizing out. Temperatures of
from 0 to 50C, especially ambient temperature, have
proved advantageous. The amount of water used for
dilution should be such that the desired product precipi-
tates substantially quantitatively. The amount of
water can be from 2 to 100 times the-amount of acid. but
for practical reasons it has proved most advantageous to
o dilute the acid extract from 5-fold to 10-fold. The
temperature during dilution îs relatively unimportant,
but it is to be borne in mind that some of the substances
to be precipitated have a low melting point and may
therefore precipitate as oils. possibly including impuri-
ties, i~ the temperature is too high, and also that on
increasing the temperature the chemical resistance of the
pyrazole compounds to aqueous acid may decrease. For
this reason. the dilution is in general carried out at
from 0C to 50C, most simply at ambient temperature.
The dilution may be carried out by adding the water to
the acid. but in general it has proved better to run the
acid into the water, with thorough stirring. Hereupon,
only the desired pure pyrazole compound precipitates.
whilst all other dissolved substances remain in solution.
The pure product can then be filtered off, for
example on a large suction filter, and be washed with
water; the odor of the product thus obtained is so
neutral that it is even possible to employ manual labor
to shovel the product out of the filter and, if desired,
, .., ,. . - ~
- 10 - O.Z. 0050/03351
charge it into a dryer.
If, however, the product is to be redissolved in
an organic solvent for further conversion, it can of
course be extracted with the desired solvent directly
after precipitation from the dilute aqueous acid solu-
tion. provided the solvent is immiscible with water.
From a chemical point of view. the basis of the
process according to the invention i.s that in the first
purification stage the weakly basic pyrazole compounds,
o which are surprisingly stable to acid. dissolve in the
concentrated acid together with other polar compounds. or
compounds capable of salt formation. present in the reac-
tion mixture, whilst the non-polar substances either
remain in the organic solvent or, iP the latter is not
used, can be filtered off as a solid residue. A
further chemical basis of the process is that the strongly
acidic dissolved pyrazole acid addition salts redissociate
into acid and pyrazole compound in a second purification
stage merely on diluting the acid solution, whilst all
other polar and salt-like compounds remain dissolved in
the dilute acid produced on addition of water. It is `~
this two-fold purification which results in the high
degree of purity of the end products.
The process according to the invention is excep-
tionally suitable for isolating the pyrazole compounds
from their crude reaction solutions and can also be
handled very easily on a pilot-plant or production scale.
The process according to the invention can be employed
easily even for purifying large quantities of contaminated
~L2~ 3
~ O.Z. 0050/033518
pyrazole compounds. Using the novel process, even
batches which have miscarried, ie. in which the reaction
whereby the pyrazole compounds are prepared has not taken
place properly. can be treated so as to isolate satis-
~actorily the valuable pyrazole compounds. which may
frequently only be present in small amounts in such
batches.
Furthermore, the process can also be used to
purify pyrazole compounds which have been prepared by a
o simplified process. Xt is known that pyrazole com-
pounds may be prepared by reacting a compound of the
general formula
~ _ /c~2-x
R2 1 \C-C~12X
R 0
where R, Rl, R2 and X have the above meanings, with a
pyrazole of the general formula
R3
~ ~4
H~
where R3 and R4 have the above meanings. in the presence
or absence of a compound which binds hydrogen halide and
in the presence of an inert solvent. ~Te have found
that the manipulation of substantial amounts of N-halo-
acetyl-N-halomethylanilines is extremely unpleasant and
not without hazards. The substances are in general
solid and cannot be pumped or conveyed through closed
pipelines. Their vapors have a strong irritant action
.2~3
- 12 - O.Z. 0550/03351~
on mucous membranes and contact with their dust can cause
skin rashes. As an expert can readily see merely from
their chemical formula. the compounds can eliminate the
toxic gases formaldehyde and hydrogen chloride on contact
with water, moist air. mucous membranes or moist skin.
. For these reasons, substantial amounts of such
compounds can only be processed if expensive safety
measures are taken.
Several methods ~or the preparation of these com-
pounds are known. A simple method (U.S. Patent
3,637,847) is to react an azomethine of the general
formula
Fl ~
where R, Rl and R2 have the above meanings. with a halo-
acetyl halide of the general formula
X-C~2-C x
where X has the above meanings. The azomethines are
synthesized by conventional methods from formaldehyde and
anilines o~ the general formula
R2~NH2
Rl .
where R, Rl and R2 have the above meanings, and are pur'-
fied by distillation before being used. However,
.. .. . .. .
, . . , .~ . .
~20~4~3
- 13 o.z. 0050/033518
German Published Application DAS 1.793,811 discloses that
certain azomethines, which are of particular interest as
intermediates for the preparation of pyrazole compounds,
for example the azomethine where R and Rl are each methyl
in the ortho-position to the nitrogen and R2 is hydrogen,
are not stable and cannot be used for the synthesis of
other compounds.
We have found, surprisingly. that a pyrazole com-
pound may be obtained in high purity and good yield by
reacting an aniline o~ the general formula
R
Rl
where R, Rl and R2 have the meanings given in Claim 1.
with paraformaldehyde in an inert organic solvent, dis-
tilling off water and excess formaldehyde from the reac-
tion mixture, reacting the reaction mixture with a halo-
acetyl halide and then reacting it further with a pyra-
zole of the gener~al formula
R3
R4
~/ N
where R3 and R4 have the meanings given in Claim 1, and
~ a compound which binds the hydrogen halide, and that this
: process can be carried out without having to isolate and
purify the intermediates described abovel if the pyrazole
compound is isolated from its crude solution by the pro-
.~ . . . .
- 14 - O.Z. 0050/033518
cess according to the invention. Even pyrazole com- -
pounds which are based on azomethines which according to
general ex,oerience and according to German Published
Application DAS 1,793,811 are unstable can be prepared
easily if the azomethines in question are not subjected
to purification, distillation or other m~thods of iso-
lation. but are converted further in the form of their
crude solution.
In the said process, an aniline is reacted in the
conventional manner with paraformaldehyde to give an azo-
methine, water and formaldehyde are distilled off, the
crude solution of the azomethine is mixed, in the s~me
vessel or a different vessel. with a haloacetyl halide.
a pyrazole and a binder for the hydrogen halide are added
to the mixture, the batch is treated according to the
invention with a concentrated aqueous acid and the acid
is separated off and diluted with water, whereupon the
end product precipitates in a pure form and in good yield.
Of course, the reaction mixture can be washed with water
before being treated with acid. In a particular
embodiment of the process. an aqueous base is used as the
binder for hydrogen halide. in the presence or absence of
a phase transfer catalyst. in which case the reaction
mixture is of course only treated with the concentrated
acid after having separated off the aqueous phase.
The advantages of this process are that even
unstable azomethines can be used and in particular that
the intermediate referred to above, whîch presents prob-
lems, need not be isolated. Since the entire reaction
_ . _
,
. " . , - ~
- 15 - o.Z. 0050/03351~
sequence can be carried out in one or two closed appara-
tuses, without requiring intermediate isolation or work-
ing-up operations. the operatives do not come into contact
with the dangerous intermediates~ As is known to those
skilled in the art, i~ in a multi-stage reaction the pro-
ducts of the individual reaction steps are not isolated
and purified, the impurities ultimately accumulate to an
extent that isolation and purification of the end product
become difficult. This, however, is not so in the
lo present case, since the crude product can easily be puri-
fied by the process according to the invention.
The process according to the invention for the
purification of pyrazole compounds is of course also suit-
able for the purification of crude solutions which have
been obtained by other methods, for example as described
in German Laid-Open Application DOS 2,704,281, and, in
these cases also, very greatly reduces the labor involved.
The Examples which follow demonstrate the sim-
plicity and reliability of the process according to the
invention.
EXAMPLE 1
5,100 parts (by weight) of N-chloromethyl-2.6-
dimethylchloroacetanilide and ll,OOO parts of toluene are
mixed with 1,900 parts of 4-methylpyrazole and-the mix-
ture is then stirred for 3 hours at 40-60C. 2,130
parts o~ triethylamine are added and the reaction mixture
is stirred for 3 hours at 60C and overnight at room tem-
perature (20C). It is then washed twice with lO,OOO
parts of water and is extracted once with 12,000 parts of
. . _ . . . _ . .
i
L3
16 -~, o.Z. 0050/03351
~7% strength (by weight) hydrochloric acid. The
extract is run into 60.000 parts o~ water, whilst stir-
ring. and the precipitate is filtered off. After dry-
ing, 4.750 parts of 95% pure N-(L~-methylpyrazol-l-yl-
methyl)-2.6-dimethylchloroace-tanilide of melting point
98-100C are obtained.
EXAMPLE 2
540 parts of 4-me-thoxypyrazole are added to
lg300 parts of N-chloromethyl-2-ethyl-6-methylchloroacet-,
anilide and 3,000 parts of toluene. The mixture is kept
at 60C for 4 hours, 500 parts of triethylamine are added,
and the batch is stirred at 60C for 4 hours and overnight
at room temperature. It is then diluted, with stirrinO,with
2,000 parts of water and the crys-tals which thereupon pre-
cipitate are filtered off, washed with water and dried to
give 750 parts o~ pure N-(4-methoxypyrazol-l-yl-methyl)-6-
ethyl-2-methylchloroacetanilide of melting point 96-97C.
The organic phase of the filtrate is separated off and
extracted once with 950 parts of 37 % strength hydro-
chloric acid. m e crystals which precipitate on adding
the extract dropwise to 6,000 parts of water are filteredoff and dried to give a further 660 parts of N-(4-methoxy-
pyrazol-l-yl-methyl)-2-ethyl-6-methylchloroacetanil-'de,
which is 98 ~o pure and has a melting point of 92-93C.
EXAMPLE 3
a) 14 parts of 94 % pure N-(pyrazol-l-yl-methyl)-
2,6-dimethylchloroacetanilide of melting point 72-75C,
the purity of which was determined by proton resonance
spectroscopy9 are dissolved in 140 parts of toluene and
- 17 - o.z. 0050/0335~8
the solution is extracted once by shaking with 40 parts o~
60 % strength sulfuric acid. m e sulfuric acid extract
is run into 240 parts of water with thorough stirring
and the crystals ~hich have precipitated are filtered off,
washed with water and dried. 11 parts of 100 % pure
N-(pyrazol-l-yl-methyl)-2,6-dimethylchloroacetanilide,
of melting point 83C, are obtained.
b) 14 parts of 94 % pure N-(pyrazol-l-yl-methyl)-
2,6~dimethylchloroacetanilide are dissolved in 140 parts
of toluene and the solution is extracted with twice 40
parts of 50 % strength sulfuric acid. m e combined
sulfuric acid extracts are hydrolyzed with water. The
precipitate ~ormed is filtered off, washed with water and
dried, giving 13 parts of a 100 % pure product, of melt-
ing point 83C.
EXAMPL$ 4
a) 100 parts of a blackish brown smeary material
which had resulted from a synthesis of N-(pyrazol-l-yl-
methyl)-296-dimethylchloroacetanilide which did not
proceed properly are stirred thoroughly with 180 parts
of 37 % strength hydrochloric acid for half an hour.
After filtering, the filtrate is extracted with 50 parts
of toluene and the hydrochloric acid
solution is added dropwise to 1,000 parts by weight of
water. After filtration and drying, 60 parts of 93 %
pure N-(pyrazol-l-yl-methyl)-2,6-dimethylchloroacetanilide
of melting point 77C are obtained.
b) 100 parts of the smeary material referred to
under a) are thoroughly stirred with 150 parts of toluene
_ . . .
- 18 - O.Z0 0050/0335~
and the mixtureis ~iltered. The filtrate is extracted
once by shaking with 180 parts of 37 % strength hydrochlo-
ric acid. m e hydrochloric acid phase is added drop-
wise to 900 parts of water and the product is filtered
o~f and dried. 54 parts of 97 % pure N-(pyrazol-l-yl-
methyl)-2,6-dimethylchloroacetanilide of melting point
78C are obtained.
c) 100 parts of the smeary product referred to under
a) are dissolved in 180 parts of methylene chloride and
o this solution is extracted first with 180 parts and then
with 60 parts of 37 % strength hydrochloric acid. m e
combined hydrochloric acid extracts are washed once with
50 parts of toluene to remove methylene chloride. m ey
are then hydrolyzed as described under a) and b), and
56.5 parts of more than 99 % pure N-(pyrazol-l-yl-methyl)-
2,6-dimethylchloroacetanilide, of melting point 83C,
are obtained.
EXAMPLE 5
A crude solution of 133 parts of N-(2,6-dimethyl-
phenyl)-methyleneimine in a toluene-cyclohexane mixture
is added dropwise to a solution of 202 parts of bromo-
acetyl bromide in 150 parts of naphtha. Since, instead
of the desired crystalline N-bromomethyl-2,6-dimethyl-
bromoacetanilide, only an oil which is difficult to isol-
ate precipitates, 450 parts o~ toluene and 75 parts of
pyrazole are added, the mixture is heated at 60C ~or 2
hoursand 110 parts of triethylamine are added dropwise,
after which the mixture is hea~ed at 60C, washed with
water, then with 5 % strength hydrochloric acid and then
. .
, . . ~
:
~Q~
- 19 - o.Z. 0050/033518
again with water, and evaporated, 248 parts of a viscous
oil being obtained. The latter is dissolved in 500
parts of toluene and the solution is extracted with
250 parts of 37 % strength hydrochloric acid. The
extract is hydrolyzed by means of 1,500 parts of water,
giving 190 parts of N-(pyrazol-1-yl-methyl)-2,6-dimethyl-
bromoacetanilide of melting point 86C.
EXAMPLE 6
1,620 parts of water are removed from a mixture
of 10,890 parts of 2,6-dimethylaniline and 4,050 parts of
paraformaldehyde by refluxing with 50,000 parts of a
toluene-cyclohexane mixture in the conventional manner.
After having been rapidly cooled to room temperature,
the resulting solution of N-(2,6-dimethylphenyl)-methylene-
imine, still containing impurities, ls reacted in the
conventional manner with 10,800 parts of chloroacetyl
chloride in 10,000 parts of toluene. 6,800 parts of
pyrazole are then added, the mixture is stirred for
5 hours at 50C, after which 10,000 parts of triethyl-
amine are added and the reaction mixture is stirred for
5 hours at 50C and overnight at room temperature. It
is then washed with 30,000 parts of 5 % strength hydro-
chloric acid and the organic phase is separated off and
extracted with 30,000 parts of 37 % strength hydrochloric
acid. The extract is stirred into 180~000 parts of
; water. The precipitate formed is filtered off, washed
with water and dried
17,840 parts of-96 % pure N-(pyrazol-l-yl-methyl)-
2,6~dimethylchloroacetanilide~ of melting point 78C,
.,~ . ~
~ "
- - ,
~2~3
- 20 - O.Z. 0050/03351
are obtained.
EXAMPLE 7
121 parts o~ a heavily contaminated batch of
N-(pyrazol-l-yl-methyl)-2-ethyl-6-methylbromoacetanilide
are dissolved in 300 parts of toluene, the solution is
extracted with 200 parts of 37 % streng-th hydrochloric
acid and the extract is hydrolyzed with water. 67
parts of the pure product, of melting point 71-73C,
are obtained.
EX~PLE 8
900 parts of water are removed from 6,050 parts
of 2,6-dimethylaniline and 2,400 parts of paraformaldehyde
with the aid of a toluene-cyclohexane mixture, as
descri~ed in Example 6, m e resulting solution is
added to 6,000 parts o~ chloroacetyl chloride in 6,000
parts of toluene, after completion of the reaction
3,800 parts-of pyrazole are added, the mixture is kept at
50C for 4 hours, 5,500 parts of triethylamine are added
and the batch is then heated ~or 6 hours at 50C. It
is then washed with dilute (5 % strength) hydrochloric
acid and ~iltered to remove a small amount of residue.
The toluene phase of the filtrate is extracted with twice
13,000 parts of 60 % strength sulfuric acid. The
extract is stirred into 300,000 parts of water. The -
precipitate formed is filtered off and dried, giving
8,800 parts of 98 % pure N-(pyrazol-l-yl-methyl)-2,6-
dimethylchloroacetanilide, of melting point 81-83C.
EXAMPLE 9
18 parts of water are removed from 121 parts of
.
~2~4~
- 21 - O.Z. 0050/033518
2,6-dimethylaniline and 45 parts of paraformaldehyde in
250 parts of a toluene-cyclohexane mixture, as described
in Example 6. After having been rapidly cooled to room
temperature, the resulting solution of N-(2,6-dimethyl-
phenyl)-methyleneimine is reacted in the conventional
manner with 113 parts of chloroacetyl chloride in 100
parts of toluene and the batch is then stirred for a
further ~ hour at 80C. A mixture of 44 parts of
NaOH, 75 parts of pyrazole and 6.8 parts of a mixture of
35 % by weight of dimethyldibenzylammonium chloride,
15 % of trimethylbenzylammonium chloride, 40 ~0 of water
and 10 % of methanol in 200 par-ts of water is then added
dropwise, after which the batch is stirred for 4 hours at
room temperature. After having separated the organic
phase from the water, the former is washed twice with
200parts of water and then extrac-ted once with 350 par-ts
and thereafter with 175 parts of 55 % strength sul~uric
acid. The combined sulfuric acid extracts are stirred
into 3,000 parts of water and the precipitate formed is
filtered off, washed with water and dried under reduced
pressure at 50C.
210 parts of 98 % pure N-(p~razol-l-yl-methyl)-2,6-
dimethylchloroacetanilide, of melting point 82C, are
obtained.
