Note: Descriptions are shown in the official language in which they were submitted.
9~
This invention concerns a process for
the preparation of 3,6-dichloropicolinic acid.
3,6-Dichloropicolinic acid is a crystalline
solid melting at 150~-152C. useful as a pesticide and spe-
cifically adapted to be employed for the control of in-
sects, mites, trash fish and microbes. The compound
is also useful as a plant growth control agent. The
compound is disclosed in U~S. Patent 3,317,549.
The 3,6-dichloropicolinic acid is taught in
the above patent to be prepared by the acid hydrolysis
of 3,6-dichloro-2~(trichloromethyl)pyridine. The 3 r 6 ~
dichloro-2-(trichloromethyl)pyridine is mixed with either
nitric~ phosphoric or sulfuric acid and the mixture main-
tained or from 1/2 to 2 hours At 20C to 140C.
While the above procedure gives high yields of
the desired product, the overall process is very expensive
due to the high cost of the starting material.
The present invention provides a process for
the preparation of 3,6-dichlor~picolinic acid which
comprises (1) reacting 3,5,6-trichloro-4-hydrazinopicolinic
acid with an alkali metal hydroxide in a liquid reaction
medium comprising water or a lowex alkanol and (2) acidifying
the reaction mixture with a mineral acid. This process
gives hlgh yield of desired product and permits more
economical production than the prior art process.
Generally, the reaction i5 carried out at a
temperature within the range of from 60 to 120C, ~onveniently
at reflux temperature, i.e. the boiling temperature of the
reaction mediumO The time of reaction varies with temperature;
reaction is usually completed in 0O5 to 3.0 hours.
~ ~'
17,521A-F 1- ~
.. . . .
' ~LO~
Representative alkali metal hydroxides which can
be employed include sodium, potassium, cesium, lithium and
rubidium hydroxides. It is usually desirable to employ
an excess of the alkali metal hydroxide.
Representative mineral acids for use in the
practice of this invention include, among others,
hydrochloric acid, sulfuric acid, and phosphoric acid.
The liquid reaction medium employed in carrying
out the process of this invention comprises water or
a lower alkanol. Representative lower alkanols include
methanol, ethanol, propanol, isopropanol and butanol.
Preferably, the reaction medium consist of a mixture
of water and ethanol.
The 3,6-dichloropicolinic acid product, in the
form of the alkali metal salt, can be recovered as such
by conventional techniques of solvent extraction or crystal-
lizationO In most cases it is more conven1ent to recover
the product in the acid form. In such cases, the above
reaction mixture is cooled and treated with a mineral acid
employing conventional acid hydrolysis conditions, In
order to insure complete conversion, acidi~ication is usually
carried to pH of 2 or less. The solid product can
be separated by filtration or other conventional solid-
-liquid separatory procedures. If desired,~the acid product
can be further purified by washing with one or more
solvents such as water, methanol, ethanol, benzene, ~-
or hexane.
The 3,5,6-trichloro-4-hydrazinopicolinic acid
starting material can be prepared by various prosedures.
For exampl~, it can be prepared by reactiny tetrachloropicolinic
17,521A-F -2-
.. . .- ..
, - . ,. l - , :. . :
509~9
acid with hydrazine in the presence of an alkali
metal hydroxide or carbonate in water. In carrying
out this reaction, the tetrachloropicolinic acid,
alkali metal hydroxide or carbonate and hydrazine
are added to water with agitation and heated under
reflux conditions for from 15 minutes to :2 hours.
The reaction consumes the reactants in
stoichiometric proportions; howeverl in order to insure
completion of the reaction, it is pre~erred that a
slight excess, 5 to 20 percent, of both the alkali
metal hydroxide or carbonate and hydrazine be employedO
At the completion of this reaction, the thus
formed 3,5,6-trichloro-4-hydrazinopicolinic acid alkali
me~al salt can be separated if desired, or the
lS preparation of the 3,6-dichloropicolinic acid can be
carried out in situ. If separation is desired and
an alkali metal hydroxide was employed to convert
the acid to the salt, the xeaction mixture must be
treated with an additional molar equivalent of alkali
metal hydroxide to remove the hydrogen chloride
by-product. If on the other hand, an alkali metal
carbonate was employed for the salt formation, the
hydrazino compound can be immediately separated as the
alkali metal bicarbonate by-product acts as a hydrogen
chloride acceptor. If it is desired to convert the sa~t
form of the compound to the acid form, such can be
achieved by conventional practices of treating the salt
with a mineral acid.
Following is an example of the preparation of
3,5,6-trichloro-4-hydrazinopicolinic acid by the abov,e
procedure.
.
17,521A-F -3-
~315~9~9
To a reaction flask was added 26.1 grams ~0.1
mole) of tetrachloropicolinic acid, 200 milliliters of water,
3.6 grams o 95 percent h,ydrazine (0.11 mole~ and 10.6
grams (0.1 mole) of sodium carbonate. The mixture was
heated with stirring and maintained under reflux conditions ~`
for about 1 hour. The reaction mixture was cooled to
25CJ and 25 milliliters of 5N HCl was aclded. The solid
which precipitated was recovered by filtration, and washed
successively with water, ethanol, benzene, and hexane
and air dried. The product was recovered in a yield of
25.6 grams ~93%) having a melting point of 165-170C. After
recrystallization from a 50:50 dimethylformamide:water
mixture, the product (as the no-hydrate) was found
by analysis to have carbon, hydrogen and nitrogen contenks
of 26.6, 2.1 and 15.3 percent, respectively, as compared
with the theoretical content~ of 26.2, 2.2 and 15.3
percent, respectively.
Alternatively, the 3,5,6-trichloro-4-hydrazino-
picolinic acid startiny material can be prepared by reacting
tetrachloropicolinonitrile with hydrazine in presence
o~ a liquid reaction medium and an HCl acceptor, ~ollowed
by acid hydrolysis of the thus formed 3,5,6-trichloro-
-4-hydrazinopicolinonitrile.
In sarrying out this reaction, the tetraahloro-
picolinonitrile is reacted with hydra2ine in a reaction
medium and in the presence of a hydrogen chloride acceptor
at a temperature of from 25C up to the reflux conditions
for from 15 minutes to 2 hours.
The reaction consumes the reactants in s~oich- -~
iometric proportion~, howeveF, in order to insure
~:.
17,521A-F _4_
105~98~31
completion of the reaction, it is preferred that a
slight excess, e.g. 5 to 20 percent, of the hydrazine be
employed.
Representative reaction medium~ include the
lower alkanols, methanol, ethanol, propanol, isopropanol
and butanol, tetrahydrofuran, dimethylformamide and pyridine.
Representative hydrogen chloride accepto;rs include among others,
aliphatic tertiary amines, such as trimethylamine, triethylamine,
or tripropylamine and aromati~ amines, such as dime~hylaniline
diethylaniline, or pyridine.
At the completion of the reaction, the thus
formed 3,5,6-trichloro-4-hydrazinopicolinonitrile
intermediate can be separated if desired. I~ ~eparation
is desired, the reaction mixture i~ cooled and quenched
with ice and/or cold water. The product which precipitate~
upon quenching can be separated by filtration, water
washed and dried. If desired, the product can be further
purified by recrystallization from a solvent su~h as benzene,
or pyridine or mixtures thereof.
The 3,5,6-trichloro-4-hydrazinopicolinonitrile
(separated or in situ) i8 reacted with an acid hydrolysi~
agent such as concentrated sulfuric acid ~olutions or
concentrated hydrochloric acid. This reaction is
carried out with agitation at a temperature of from
~25 80C. to 150C. for from 30 minutes to 2 hours. Thereaf er,
the reaction mixture is cooled and quenched by pouring
over ice. ~ -
The 3,5,6-trichloro-4-hydrazinopicolinic acid
product precipitates upon quenching and can be recovered
~30 by filtration or other conventional solid-liquid separatory
procedures, washed with water and dried.
.`'' ' ~.,'.
17,521A-F -5- ~
~L~S~g~9
Example 1
. .
To a reaction flask co~taining 200 milliliters of
water was added 26.1 grams (0.10 m~le) of tetrachloropicoli~
nic acid, 3.6 grams (0.11 mole) of hydrazine and 10.6 grams
(0.1 mole) of sodium carbonateO The mixture wa~ stirred and
heated under reflux conditions for 1.5 hours. To this mix-
ture was added dropwise over 15 mi~utes 6.0 grams ~0.15
mole) of sodium hydroxide dissolved in 25 milliliters of
water. The mixture was heated under reflux for one hour.
The reaction mixture was cooled to 30C and acidified with
10 milliliters of concentrated hydrochloric acid. The 3,6-
-dichloropicolinic acid was collected by extracting the re-
action mixture 3 times with 150-milliliter portions of
methylene chloride, combining the extracts, and removing
the solvent by evaporation. The product was obtained in
a yield of 14.9 gram3 (78%~ with a 3,6-dichloropicolinic
acid purity o~ 90 percent.
Exam~le 2
To a reaction fla~k containing 300 milliliters
each of water and ethanol u~der a nitrogen atmosphere
was added 60 grams (0023 mole) of 3,5,6-trichloro-4-
-hydrazinopicolinic acid. The mixture was heated to re-
flux and 60 milliliters of a 50 percent aqueous sodium
hydroxide solution was added over 3 minutes. After an
additional 45 minutes of heating undèr reflux, the reaction
mixture was cooled to about 30C, and 100 milliliters of
concentrated hydrochloric acid was added. The ethanol
was removed from the reaction mixture by evaporation under
reduced pressure, and the solid 3,~-dichloropicolinic acid
product was recovered by ~iltration and dried. The product
17,521A-F -6-
~5Q9~
was obtained in a yield of 23.5 grams (58~) and was
found by quantitative vapor phase chromatographic analysis
to be 9806 percent pure 3,6-dichloropicolinic acidO
The filtrate from the a~ove filtration step
was extracted 3 times with methylene chloride (portions
equal to 150, 100, and 100 milliliters, respectively) and
the combined extracts were dried over magnesium ~ulfate.
The solvent was removed by evaporation leaving 11.8 grams
of a solid which by analysis was found to be 70 percent
pure 3,6 dichloropicolinic acid.
Example 3
To a reaction flask containing 400 milliliters
of water was added 30 grams (0.11 mole) of 3,5,6-trichloro-
-4-hydrazinopicolinic acid and 4.5 grams (0.11 mole)
o sodium hydroxide dissolved in 25 milliliters of water.
The reaction was heated to reflux and maintained under
reflux while an additional 4.5 grams of sodium hydroxide
dissolved in 25 milliliters of water was added dropwise
over 50 minutes. The resulting solution was thereafter
heated an additional 45 minutes under reflux ana cooled
to room temperature. The reaction mixture was mixed
with 100 milliliters of methylene chloride and the solution
acidified with 35 milliliters of concentrated hydrochloric
acid. The two phases which fQrmed were separated and the
aqueous layer extracted twice with methylene chloride.
The extracts were combined and dried over magnesium sulfate
and the solvent evaporated to give 13.1 grams ~62~ yield)
of 3, 6-dichloropicolinic acidO ~ :
17,521A-F -7-
