Note: Descriptions are shown in the official language in which they were submitted.
7~
The pres.ent invention relates to a process for the
manufacture of 3,5-disubstituted pyrazoles. ~ore particularly,
the invention provides a method for the preparation of 3,5-di-
substituted pyrazole ~aving the formula:
R2 ~ 1
N ~--N-H
wherein R~ nd ~2 is - ~
Z Z .,
said Y, Y', Z and Z' each represents a member selected from the :~
group consisting of hydrogen, halogen, methylthio, methyl-
sulfonyl, cyano, carboxyl, car~oalkoxy Cl-C4, hydroxy, alkyl ..
Cl-C4, haloalkyl Cl-C4 containing 1 to 4 halogen atoms and .. -
10 alkoxy Cl-C4 which comprises the steps of: reacting approxim- .
ately equimolar amounts of a compound having the formula RlCOCH3 .. ~.
with a compound having the formula R2CHO, wherein Rl and R2 are .~
as defined above, in the presence of a base and a Cl-C4 !: .
alcoholic solvent at a temperature ranging between about 10C. ~
and 70C., acidifying said reaction mixture to a pH of 5 to 7, :.
treating the so-acidified reaction mixture with from about : ;
1.0 to 2.0 mole equivalents of hydrazine, adding to said
: reaction mixture a catalyst selected from the group consisting ~: :
,.
of palladium on carbon, platinum on carbon and pre-reduced
20 copper chromite, heating said mixture to refluxing temperatures, -;.
and recovering the desired 3,5 disubstituted pyrazole in good .. .~.
yield and purity. .~
In general, the overall reaction can be illustrated .. ; :
graphically as follows~
~3~
o
(I) RlCOCH3 ~ R2CHO ~ R2OEI=CHCRl -
a methyl ketone a 1,3-disub- (1) mineral
-~ an aldehyde stituted ,~_ acid, then
unsaturated
ketone (2) H2NNH2
H20
~I2 Rl ~ R2 ,~catalyst R1 ~ 2
N ~ N-H (dehydro- N N-H
genation) --
3,5-disubstituted A disubstituted
pyrazole pyrazoline
wherein Rl is ~ ; R2 i~ ~ ; and Y, Y'~ Z and
Z z'
Z' each independently represent members selected from the
group consisting of hydrogen, halogen, methylthio, me~hyl-
sulfonyl, cyano, carboxyl, carboalkoxy Cl-C4, hydroxy, alkyl
Cl-C4, haloalkyl Cl C4 containing 1 to 4 halogen atoms, and ~ .
alkoxy Cl-C4. : -
,'. ', ,
,. ... . .
: ,. :
",' ,, ~ :.
:. ~' ,. '
' ~
. " ':: ' -' . ' ,
' ~,
~,: ' : ,
.:: .. ' .
,.' .',, .
-la~
.: '' - ' ' .
; V, -"
~L037~14B
The term "halogen", as herein used, is intended to
mean ~luorine, chlorine, iodine or bromine; however, fluorine,
chlorine and bromine are preferre~. -
The terms "alkyl" and "alkoxy" are intended to mean
straight chain and branched chain alkyl and alkoxy, includ-
ing straight and branched haloalkyl, and straight and branched -
carboalkoxy.
In accordance with the process of this invention, ap-
proximately equimolar amounts of the ketone, RlCOCH3, and
the aldehyde, R2CHO, are charged to a reactor along with a
quantity of a Cl-C4 alcohol, preferably methanol. Approxi-
mately one-half mole of base per mole of ketone is then
slowly added to the reaction mixture while maintaining the
temperature thereof between about 10C. and 70C., and pre-
ferably between 20C. and 30C.
Exemplary bases include, for instance, alkali metal
Cl-C4 alkoxides, such as sodium or potassium methoxide,
ethoxide, propoxide, butoxide, t-butoxide, and equivalents
thereof, or aqueous sodium hydroxide or potassium hydroxide.
Aqueous sodium hydroxide is, however, generally preferred.
The aforementioned ketone-aldehyde mixture is
stirred, usually for several hours, and then acidified to
a pH of 7 or below, preferably to between 5 and 7, utilizing
a mineral acid such as hydrochloric acid, sulfuric acid or ~ -
:: ,
phosphoric acid. In practice, it will usually be found that
,,- ,:
the mole ratio of acid required for pH adjustment will ap-
proximate the mole ratio of base employed in the previous
reaction.
Subsequent to acidi.fication, the reaction mixture
is treated with at least one mole~equivalent; and preferably
an excess, i.e., up to 100~ excess or 2 mole equivalents,
,~
~ - 2 -
:
~0371D4L8
of hydrazine. The hydrazine employed may be anhydrous or
in aqueous solution, and should be introduced into the re-
action mixture in such manner as to maintain the temperature
thereof below 70C. and, preferably, between 20C. and 30C.
Since the reaction is exothermic, cooling is generally re-
quired to maintain the latter temperatures. Further, the re-
action is preferably carried out in an inert atmosphere in
order to exclude air from the reaction mixture and, thus,
prevent any oxidation of the intermediate pyrazoline. This
can be achieved by conducting said reaction under a blanket
of an inert gas, such as nitrogen, helium, argon or carbon
dioxide. In general, the hydrazine addition period should
be relatively rapid, since prolonged additions result in
lower product yield. It is a good practice to complete the
hydrazine addition within about sixty minutes, or less, both
in a batch or continuous operation.
Following the hydrazine addition, the reaction mix- -
ture is heated to reflux, and subjected to catalytic dehydro-
genation. This catalytic dehydrogenation reaction is prefer-
ably carried out in an inert atmosphere, as for example,
under a blanket of nitrogen~ argon, helium or carbon dioxide.
However, the provision for an inert atmosphere is not abso-
lutely essential, although it does improve product yield.
The dehydrogenation can be carried out in a variety of se-
lected solvents or solvent mixtures by first distilling off
the alcohol and replacing it with the selected solvent. The
preferred solvent is xylene or mixed xylenes. However, other
solvents are suitable. Exemplary solvents include, for in-
stance, (a) benzene, toluene, heavy aromatic solvents, such
~ 3a as PANASOL~ AN-2, AN-3 or AN-5, ESSO H~N~, SOCAL 44 L, and
;~ the like, which have a mixed aniline point above 30F. but
-
- 3 _
~7~
not exceeding 95F., an aromatic content be-tween 60% and
lOO~i and a specific gravity at 60/60F. betwéen 0.88 and
1.5; (b) cyclic ethers such as dioxane and tetrahydrofuran
(THF); (c) polar aprotic solvents such as acetonitrile and
dimethylformamide (D~F); or (d) chlorinated hydrocarbons,
such as chloroform, perchloroethylene or ethylene dichloride.
After the alcohol solvent is removed by distillation, and
the selected solvent from the above-mentioned group of sol-
vents, preferably xylenes or mixed xylenes, is added, the
reaction mixture is cooled to between 40C. and 70C., and
washed with water to remove alkali metal salts, alcohol and
any unreacted hydrazine. In the preferred procedure, a cata-
lyst, such as platinum or palladium on carbon, or prereduced
!
copper chromitei, is added to the reaction mixture while main-
taining an inert gas flow over the reaction mixture. In -
practice, the catalyst should be introduced to the charge (at
a temperature between 40C. to 60C.) as a water wet solid
or admixed in a solvent as a slurry.
The overall reaction mixture is then brought to re- ;
flux and residual water removed by azeotropic distillation.
Refluxing is continued while maintaining an inert yas flow
to insure both complete removal of hydrogen gas from the re-
action system and to obtain completion of the reaction. ~When,
.: .
for instance, prereduced copper chromite is used as the speci-
fic dehydrogenation catalyst, a reaction temperature of about
200C. is requiredt and, therefore, a heavy aromatic solvent
;with a minimum boiling point of about 200C. is used.
After completion of the dehydrogenation stage, the
catalyst can be removed by filtration at a temperature of
about 130C., or at a lower temperature, 95C. to 110C.,
by the addition of a co-solvent such as dimethylformamide in
:~
which the product 3,5-disubstituted pyrazole is more soluble.
- - 4 -
~C~37a~;L8
The filtrate is cooled, preferably to about 10C., and the
3,5-disubstituted pyrazole, prepared by the above reaction,
is then separated from the filtrate. Separation may be ac-
complished by any convenient means, as for example, by cen-
trifugation or filtration.
As an alternative procedure, the dehydrogenation mix-
ture from the above reaction containing the 3,5-disubstituted
pyrazole and the catalyst, can be employed directly without
separation in the preparation of l-alkyl-3,5-disubstituted
pyrazoleO This eliminates the need for a hot catalyst fil-
tration, because the l-alkyl-3,5-disubstituted pyrazole is
extremely soluble in the reaction solvent, and the catalyst
can then be removed after the alkylation step merely by room ~;
temperature filtration. The catalyst can then be recycled
to prepare another batch of 3,5-disubstituted pyrazole.
As hereinabove mentioned, catalytic dehydrogenation
can also be carried out in a Cl-C4 alcohol, preferably metha-
nol or ethanol, employing palladium on carbon or platinum
on carbon as the catalyst. This procedure does not require
distillation of a portion of the alcohol and substitution
thereof with a solvent, such as xylene or mixed xylenes. How-
ever, dehydrogenation in alcohol proceeds more slowly than
it does in the preferred co-solvent system, and product
yields are generaIly lower than those obtained with said
~system. These results are primarily due to the lower boiling
point of the alcohol, and to the greater solubility of 3,5-
disubstituted pyrazole in alcohol. After a hot filtration
to remove the catal~st from the reaction mixture, resultant
mi~ture is cooled to about 10C. The pyrazole precipitates
and can be separated by filtration or centrifugation. If de-
sired, water can be added to the reaction mixture, after sepa-
ration of the catalyst, to improve pyrazole precipitation ~
.',:
- 5 - ~ ~
~ai3Y~
and separation from the reaction mixture.
The 3,5-disubstituted pyrazoles prepared in accord-
ance with the process of this invention have a variety of
uses, among which is the utilization thereof as intermedi-
ates for the preparation of 1,2-dialkyl-3,5-disubstituted
pyrazolium sa]ts, such as 1,2-dimethyl-3,5-diphenylpyrazolium
methyl sulfate. These pyrazolium salts are highly effective
herbicidal agents and are particularly effective for the
selective control of wild oats in the presence of small
grains such as barley, wheat, rye and rape.
As previously stated, resultant 3,5-disubstituted
pyrazole can be converted to a corresponding l-alkyl-3,5
disubstituted pyrazole by reacting it with an equimolar
amount or e~cess (i.e., 1 to 1.5 moles) of an alkylating
agent in the presence of a solid, anhydrous, inorganic alkali
metal base and a non-aqueous, inert, organic solvent. The
reaction is carried out at a temperature between about 50C. -
and 175C., and preferably between 85C. and 120C.
Suitable alkylating reagents include alkyl halides,
dialkyl sulfates, alkyl phosphates, alkyl hydrogen sulfates,
or alkyl toluene sulfonates; wherein said alkyl groups con-
tain from 1 to 4 carbon atoms. Among the preferred alkylat-
ing reagents are alkyl halides, such as methyl, ethyl,
n-propyl, isopropyl, n-butyL and isobutyl chlorides and bro-
mides; dialkyl sulates-, such as dimethyl sulfate and alkyl
; ~toluene sulfonates, such as methyl p-toluene suIfonate.
Illustrative solvents which may be employed herein
are non-aqueous, inert, organic solvents, preferably se-
;~ lected from aromatic hydrocarbons, such as toluene and xylene;
aliphatic hydrocarbons such as hexane and heptane; ketones
having ~rom 4 to 7 carbon atoms, such as methyl isobutyl ke-
tone, cyclohexanone, or the like; alcohols having from 2 to
: : . '
,'.
~iL03~
8 carbon atoms, and preferably 3 to 4 carbon atoms; dipolar
aprotic solvents, such as dimethyl sulfoxide, dimethyl forma-
mide, acetonitrile, nitrobenzene, N,N-dimethylacetamide,
tetrahydrosulfolane; ethylene dichloride; and alkoxyalkyl
ethers such as dioxane and tetrahydrofuran.
Suitable bases are solid, anhydrous, inorganic,
alkali metal bases. They are strong bases, and preferably
selected from the group consisting of sodium hydroxide,
potassium hydroxide, sodium carbonate, potassium carbonate,
calcium oxide and calcium hydroxide.
Conversion of the 3,5-disubstituted pyrazoles to
the l-alkyl-3,5-disubstituted pyrazoles can be graphically
illustrated as follows:
(II) ~ a (R3)mQ + ~e ~ Rl--~
P~ . , ' ' .
wherein Rl and R2 are as defined above in (I); R~ is an
alkyl radical of from 1 to 4 carbon atoms, Q is a radical :
selected from the groùp consisting of a halide, a sulfate, :
a phosphate, toluene sulfonate and a hydrogen sulfate; and
m represents an integer selected from 1 to 3.
Resultant l-alkyl-3,5-disubstitu~ed pyrazole is then
readily converted to the herbicidally active 1,2-dialkyl-3,5-
-disubstituted pyrazolium salt by quaternization of the
l-alkyl-3,5-disubstituted pyrazole. .:.~ . :
Conversion of the l-alkyl-3,5-disubstituted pyrazole
to the 1,2-dialky1-3,5 disubstituted pyrazolium salt is ::
.
achieved by reacting the pyrazole with an equimolar amount -~ ~ :
or a slight excess of an alkylating reagent (R4)mQ~ where
R4 is alkyl Cl-C4 and m and Q are as defined above. Alky-
~: : lating reagents that can be used are selected from the group .:
.,: ~,
_ 7 _ :
~LC3371)~
consisting of alkyl halides, dialkyl sul~ates, and alkyl
toluene sulfonates. They are used in equimolar amounts with
the pyrazole or in a slight excess, for example, from about
1 to 1.5 moles per mole of pyrazole.
In general, the latter reaction is carried out in
the presence of a non-aqueous organic solvent, such as xylene
or in a mixture o~ inert organic solvents consisting of (a)
a chlorinated hydrocarbon solvent, and (b) an organic solvent
selected from the group consisting of aromatic hydrocarbons,
aliphatic hydrocarbons, ketones, alcohols, alkoxyalkyl ethers,
dipolar aprotic solvents and cyclic ethers as defined above.
Preferred mixtures generally consist of from about 10~ to
90%, preferably 25% to 75%, by volume of a solvent in which
the quaternized 3,5-disubstitutéd pyrazollum salt is rela-
tively insoluble, and from about 90~ to 10%, preferably 75%
to 25%, of a solvent in which the quaternized 3,5-disubsti-
tuted pyrazolium salt is relatively soluble, Preferred co-
-solvent systems meet the above requirements as to percent
composition, and are selected from aromatic hydrocarbon sol-
vents in admixture with chlorinated hydrocarbon solvents or
aliphatic hydrocarbon solvents in admixture with chlorinated
hydrocarbon solvents. Particularly advantageous are xylene-
-ethylene dichloride mixtures. The latter compositions are~
especially useful, since they provide a readily filterable,
.
flowable slurry from which the quaternized 3,5-disubstituted -
pyrazolium salt is readily recovered. The use of the co- ;
-solvent system assures excellent yields of very high purity -~
-:
product and avoids the production of mixtures of quaternized
:: . ,:
~ 3,5-disubstituted pyrazolium salts. This alkylation is ~
..
carried out in a manner which assures that the temperature
of the reaction mixture is generally maintained between about
50C. and 175C., and preferably between 90C. and 110C.
- 8 -
~C~37~14B
The reaction mixture containing the pyrazolium
salt ls cooled and the pyrazolium salt then separated
from the reaction mixture. Alternatively, the reaction
mixture may be heated with a tertiary-amine to de~troy
residual alkylaking agent, cooled and the centrifuged or
filtered to recover the pyrazollum ~alt, Yet another
alternative i~ to extract the pyrazolium salt with water
~rom the above-mentioned reaction mixture. The water
solution thus obtained may then be employed directly in
the control of undesirable plant species.
The above reaction and the herblcidally e~fective
1,2-dialkyl-3,5-disubstituted pyrazolium salts, which can
be prepared by said reaction, ls illustrated as ~ollows:
R2 ~ Rl + (R~)mX ~ ¦ R2 ~ 1 X
N N N N
R9 _ m
where Rl, R2, R3 and R4 are as described above; X represents
an anion having a charge from 1 to 3; and m is an integer
selected from 1, 2 and 3.
Illustrative o~ the anions which are suitable for ~` -
use in the present invention may be mentioned; ~or example, ~ -
halides such as chloride~ bromide or iodide; sul~ate;
hydrogen sul~ate; methyl sulfate; benzene sul~onate; C -C ;
alkoxy benzene sulfonate; Cl-C4 alkyl benzene sul~onate,
preferably a toluene sulfonate such a~ p-toluene sulfonate; ~
pho~phate and methyl pho~phates; and alkane ~ul~onate Cl-C4. ~ ~ !
The ~ollowing examp]es are presented primarlly for
purposes o~ illustrating more specific details o~ the in-
vention which are not to be taken a~ limitative Unless
otherwlse speci~ied, the parts are by weight and the analysis -
~are ln percent.
. - _ 9 _ ~,' ~, " ,.
~3701~
EXAMPL~ 1
The preparation of 3,5-diphenylpyrazole
Acetophenone (31.85 parts), benzaldehyde (28.13
parts) and methanol (157.58 parts) are charged to a suitable
reactor, and 50% aqueous sodium hydroxide (10.61 parts) is
then added at 20~C. to 30C. The reaction mixture is
stirred for 4 hours at 20C. to 30C. After the hold period,
the resultant chalcone slurry is made slightly acidic
(pH 5 to 7~ by the addition of 36% hydrochloride acid. The
reaction mixture is cooled to -5C. to 0C. Nitrogen is
introduced over the reaction mixture, and 20.86 parts of 70%
hydrazine hydrate is added at a maximum temperature of 35C.
After the hydrazine hydrate addition, the reaction mixture
is stirred at 20C. to 30C. for one hour. Approximately
75~ to 80% of the methanol is then distilled off and re-
placed with mixed xylenes. The xylene solution ls cooled to
50C. to 60C. and washed twice with water to remove sodium
chloride, methanol and unreacted hydrazine hydrate.
After the last water wash, 2.20 parts of 5% palladi-
um on carbon catalyst is added under nitrogen, and the re-
action mixture heated to reflux ~140C. to 144~C.) and held
at reflux for 2 hours. A small amount of water is azeotro-
phically removed during the heat-up and the xylene returned
to the reactor. Hydrogen is evolved during the heat-up and
during the 2-hour hold period at reflux. After the hold
period, 15.0 parts of dimethylformamide is added and the
catalyst removed by a hot (120C.)i filtration. The catalyst
is washed with xylene and then steamed to remove trace im-
purities and recycled for reuse. Water (53.1 parts) is
added to the catalyst-free filtrate and the mi~ture cooled
to 10C. 3,5-diphenylpyrazole is filtered. About 43.2 parts
: ,
~!~137~
of 3,5-diphenylpyrazole (dry basis) is obtained. This
amounts to a 74% yield based on the acetophenone reactant.
EXAMPLE 2
The procedure of Example 1 is repeated in every
detail except platinum on carbon is substituted for palla-
dium on carbon. Substantially the same results are obtained.
In another run, prereduced copper chromite is substituted
for palladium on carbon utilizing the procedure of Example 1.
However, approximately 0.5 part of prereduced copper
chromite per gram mole of acetophenone is utilized, and the
dehydrogenation is conducted in the presence of a high boil-
ing aromatic solvent, PANASOL~ AN-2, at a temperature of
about 200C.
:
Following the above procedure, but substituting -
the appropriate ketone and aldehyde for acetophenone and
benzaIdehyde, respectively, the following pyrazoles are ob-
tained as set forth in Table I below.
: ' :
:
~ ~ 25 ~
~ , . . .
~ . ~ . . .
~ 30
:: : . ':'
~L~3~
~ABLE I
R R
~ ~ H
Rl I R2
: _ _
2-chlorophenyl phenyl
3-chlorophenyl phenyl
4-fluorophenyl phenyl
2-methylphenyl phenyl
4-t-butylphenyl phenyl
2-hydroxyphenyl phenyl ~::
3-metho~yphenyl phenyl -: ~
4-methylthlophenyl phenyl . .
3-methyl~ulfonyl- phenyl . --
phenyl - ~ .
2-chlorophenyl 3-methylphenyl .
2-chlorophenyl 2-chlorophenyl :~
3-chlorophenyl 5-chlorophenyl
2-methylphenyl 2-methylphenyl ::
4-methoxyphenyl 4-methoxyphenyl :-
2-chlorophenyl 2-methoxyphenyl
3-~luorophenyl 3-~luorophenyl
2l4-dichlorophenyl 29 4-dichlorophenyl
4-cyanophenyl 4-cyanophenyl -
3-carboxyphenyl phenyl .:
4-chloromethyl- 4-chloromethylphenyl
phenyl
3-carbomethoxy- phenyl
phenyl - _
.
- 12 - ~-` `-
,.. ~::
... .
~03~4~
TABLE I (Continued)
. ~ - - Rz --~-~~-~--~~~-~---
.. . . __ .
3,4-dimethylphenyl 3,4-dimethylphenyl
2,4-dimethoxyphenyl 2,4-dimethoxyphenyl
4-chloro-3-methylphenyl 4-chloro-3-methylphenyl
3,5-dibromophenyl 3,5-dibromophenyl
~.. ~ . .................. . . .. _ .. _ __ , , .
EXAMPL2 3
.
The_preparation of Q-(l-methyl-5-phenyl-3-pyrazolyl)phenol
. _ :
A slurry of 5~ palladium on carbon (o.6 part in
20 pQrts by volume of xylene) is added 310wly to a cooled
(5C.) solution of o-(l-methyl-5-phenyl-2~pyrazolin-3-yl)
phenol (10.5 parts) in 50 parts by volume of xylene~ and
the re~ulting suspension heated at reflux. PeriodicallyJ
samples are removed for gas, liquid chromatography (glc)
analysis. -~
When glc indicates that all of the starting material ; ~
has been utilized, the reaction mixture is cooled and filtered, ~ -
and then i~ evaporated in vacuo to give an orange-brown oil -
which slowly crystallizes, After drying thoroughly~ a
product weighing 8.1 parts is obtained with melting point - ~-
90,5C. to 9~C. This amounts to a yield of 78.2~, ba~ed
on the weight of o-(l-methyl-5-phenyl-2-pyrazolium-3-yl)
~5 phenol, ~ -
Analysis calculated for C16H14N20: C, 76-78;
H~ 5,64; NJ 11.19. Found: C, 76.60; Hz 5,72; N, 10,63. -
EXAMPLE 4 -~
. .
The preparation o~ l-methyl-3,5-diphenylpyrazole
3~ The procedure Or Example 1 is followed in every ~',,'.A.~,'.'"~ ~'
dekall except that no dimethylfo~mamide is added during the
dehydrogenation ~tep and the catalyst is not removed. --
The reaction mixture i~ coolecl to about 50C, J 2.42 parts
~ 13 - -
~b37~4~
of methyl alcohol and 11.3 parts of solid anhydrous sodium
hydroxide are added. The reaction mixture is heated to
95C. to 100C., and 29.8 parts of dimethyl sulfate are
next added. The reaction mixture is heated at reflux for
about 60 minutes, then coolPd to 80C., and 82 parts of
water are added. Fifty percent aqueous sodium hydroxide are
added to bring the pH of the aqueous phase to between 10
and 11. The reaction mixture is filtered to recover the
spent catalyst. There is no need to filter hot, bécause
the 1-methyl-3,5-diphenylpyrazole is extremely soluble in
xylene. The catalyst is washed with xylene, and water, and
then recycled to a subsequent dehydrogenation batch. The
aqueous layer is removed, the organic layer is washed with
82 parts of water, and the aqueous layer is removed. The
organic layer contains about 41 parts of 1-methyl-3,5-di-
phenylpyrazole which amounts to 89.5~ yield based on 3,5-
-diphenylpyrazole.
EXAMPLE 5
The preparation of l-methyl-3,5-diphenylpyrazole
Five parts of 3,5-diphenylpyrazole are dissolved in
25 parts (by volume) of methyl isobutyl ketone. Solid an-
hydrous sodium hydroxide (1.1 parts) is added and the mix-
ture is heated to 90C. Dimethyl sulfate (3.43 parts) is
added and the mixture is next heated to 112C. to 115C.
2S The reaction mixture is sampled after 1.5 hours, and no un-
reacted 3,5-diphenylpyrazole is found to be pre~ent~ The
reaction mixture is cooled to 50C., and 30 parts of water ',5
are added. The pH is next adjusted to between 11 and 12 by
the addition of aqueous sodium hydroxide. The organic layer
is washed twice with 30 parts water. For yield determination
the methyl isobutyl ketone is removed ln vacuo, producing
- 14 -
~L03~4B
4.95 parts ~93% crude yield) of an oil which crystallizes
on cooling (melting point 52C. to 53C.). Analysis of
the product shows it to be 85.5% pure as 1-methyl-3,5-di-
phenylpyrazole.
EXAMPLE 6
The preparation of l-methyl-3,5-diphenylpyrazole
-
Twenty parts of 3,5-diphenylpyrazole is dissolved
in 100 parts xylene containing 7.26 parts of solid anhydrous
sodium hydroxide. The reaction mixture is heated to 120C.,
and 13.8 parts of dimethyl sulfate are added. The reflux
temperature drops to 95C., and after 15 minutes at 95C.,
a reaction mixture sample indicates no unreacted 3,5-diphenyl-
pyrazole is remaining (tlc.). After 30 minutes, the reaction
mixture is cooled to 80C. and 50 parts of water are added.
Fifty percent aqueous sodium hydroxide is added to bring pH
of aqueous phase to between 10 and 11. The organic layer is
washed twice with 50 parts of water. For yield determina-
tion the xylene is removed ln vacuo, producing 19.7 parts of
an oil which crystallizes on seeding. Analysis of the prod-
uct shows it to be 98.5% pure.
EXAMPLE 7
. .,
The preparation of 1,2-dimethyl-3,5-diphenylpyrazolium methyl
sulfate
A solution of 1 mole of 1-methyl-3,5-diphenyl-pyra-
zole in xylene is prepared by following the procedure of ~-
Example 4, above. About 75% of the xylene is distilled off,
and a quantity of ethylene dichloride equivalent to the xy- -
lene remaining in the reaction mixture is added. The re-
action mixture is cooled to 60C., and 1.05 moles of ~i-
methyl sulfate are then added and the mixture is heated to
105C. to 110C. and maintained at 105C. to 110C~ for
about 4 hours. The mixture is cooled to 50C. and triethyl-
- 15 -
~1370gl~3
amine (8 mole percent based on dimethyl sulfate) is added.
The reaction mixture is stirred at 50C. for 30 minutes.
The reaction mixture is cooled to room temperature and then
filtered and washed with xylene, then with acetone, and the
product dried. A 90~ yield of product is obtained.
EXAMPLE 8
Example 7 is repeated in every detail except that
16 mole percent instead of 8 mole percent of triethylamine
based on dimethyl sulfate is employed. It is noted that a
similar yield of product is obtained.
x,~
:~ ,
;30
' ': , .,
- 16 - -~
. -
