Note: Descriptions are shown in the official language in which they were submitted.
I.I;J I~ I O ' 'J
CATALYTIC OXIDATION OF 3,3-~IMETHYL
2-HYDROXYBUTYRIC ~CID TO 2-OXO ACID
ihe present invention relates to the preparation of
3,3-dimethyl-2-oxobutyric acid ancl its salts.
United States Patent 3,905,801 discloses the conclensation
~ of ~-oxo-alkanoic acids uith thiocarbohydraæide to produce 4-
.. amino-6-(substituted)-3-thio-1,2,l~-triazin-5(4-H)-ones whici- can
be methylated to give 4-amino-6-(substituted)-3-(methyl-thio)-
1,2,4-triazin-5-(4-H)-ones of which the 6-tert. butyl derivative
lO is an especially effectlve selective herbicide of special utilit;
in the cultivation of soybeans, tomatoes, potatoes, and the like
It is disclosed in that patent that 2-oxoacids can be prepared
from the 2-hydroxy counterpart.s by oxidation with potassium
permanganate.
This process is quite acceptable and has been used success-
fuliy in making millions of pounds of the 6-tert.butyl derivative
but it is not inexpensive due to the high cost of potassium
permanganate. In addition, it results in large quantities of
by-product manganese dioxide which must be disposed oE, with
20 possible environmental impact.
It is accordingly an object of the present invention to
provide an improved process for the preparation of 3,3-dime~.hyl-
2-oxobutyric acid and/or its salts.
These and other objects and advantages are real;.zed in
25 accordance with the present invention pursuclnt to which a salt
of 3,3-dimethyl-2-oxobutyric acid is prepared by reacting 3,3-
dimethyl-2-hydroxybutyric acid with a hypochlorous salt under
alkaline conditions in the presence o:E ruthenium as catalys~.
Advantageously the salts are soclium salts al~hougl~ othcr
alkali metal and alkaline earth metal salts can be used provided
they are soluble in the reaction medium, e.g. water.
- The reaction medium is preferably o~ a pH of abou~ 9 to 13,
especially about 10 to 12. Since some hydroxyl ion appears to be
consumed during the reaction, either it is init:ially sur)plied in
excess or alkali is added durin~, oxidation to maintain the
clesired p~l. rf the pM o~ the hydroxy salt so].uti.on is below
about 6.0 or if the free caustic content of the hypochlorite
lO solution is lowered to below about 1.3%, the desired oxidation
does not proceed to any significant extent and further additlon
~;j of hypochlorite merely cleaves any keto acid which may be present.
'~ In add~ition, the Ru catalyst is converted to a water soluble form
which is difficult to recover from the solution.
The hypochlorite is advantageously ~ISed in excess to e~ re
complete conversion of the 2-hydroxyacid using about 5 to 15~
excess. The hypochlorite can be formed in situ, e.g. by bubbling
chlorine gas into an aqueous caustic solution of the hydroxy acid
containing the`catalyst.
The reaction proceeds even at room temperature but preferably
is conducted at about 40C or higher to speed it up. ~'~bove about
60C pivalic acid is produced so advantageously the oxidation is
carried out at or below 60C.
,~
, -2-
The ruthe~ m catalys~ is oxidize(ll)y t:lle hyp0ch1ori ~-e to
produce a mixture o:E ruthenate, perruthena.te ancl ruthenium
tetroxide, the ruthenate predominatin~,. At the end oE the
reaction the ruthenium oxide is an insoluble solid present in
substantially the same amount as initially so it can be filterecl
off an.d reused, even without treatment, in another cycle The
ruthenium can be supplied to the reaction solution in -the Eorm
of a salt or an oxide, ruthenium dioxide and especially ruthenium
dioxide hydrate being preferred. The oxide, for example, could
be formed in situ commencing with a salt such as ruthenium
trichloride.
The ruthenium oxide is employed in catalytic amounts, e.g.
from between 0.01g to about 1.0g per mole of hydroxyacid,
preferably between about 0.lg to 0.5g per mole.
.
The catalyst and hydroxacid salt aqueous ~luLion is
adjusted to the desired pH and the temperature brought to the
desired value. Then caustic soda and ch]orine or pre-formed
NaOCl can be added dropwise or incrementally. After all the
oxidizing agent is added the mass is maintained to ensure
20 completion of the reaction and then it is filtered to separate
the catalyst from the solution containing the product in high
yield and purity.
.
Tlle oxidation proceeds rapi~1y allcl a~l~iLion oL ~lle llyl)o-
" chlorite within only 5 minutes results in very high yields.
Advantageously, somewhat longer reactlon times are employed,
e.g. about 30 minutes or an hour, to permit the ruthenium
5 catalyst to be returned to suitable insoluble form for filtration
and then re-use in a further cycle. The resulting solution can
then be used directly for reaction with thiocarbohydrazide to
form 4-amino-6-(1~1-dimethylethyl)-3-thio-1~3~4-5(4-1~)-one
In Chemical Communi.cationsl420 (1970) it is taught that
: 10 compounds containing the grouping-CHOH-CO- undergo carbon-carbon
cleavage under ruthenium-catalyzed oxidation rather than con-
version to -CO-CO-, e.g.
-CHQH-CO ~ -CHO ~ OHC-
-CHOH-CO ~ -CO-CO-
Surprisingly, however, witll the i.nstant s~arting materia].s
and conditions of alkalinity oxidation proceeds herein by con-
version of the hydroxy group to a carbony] wlthout cleavage
between the hydroxy-bearing and carbonyl-bearing carbon atoms.
The invention will be further described in the following
20 illustrative examples wherein all parts are by weight unless
otherwise expressed: -
-
Example 1
(a) A 2 liter Morton flask equipped with a mechanical
stirrer, thermometer, condenser, and dropping funnel was
charged with 559 g of an 11.8% aqueous solution of 3,3-
dimethyl-2-hydroxybutyric acid ("hydroxy acid") as the
sodium salt (0.5 mole) and 0.2 g of ruthenium dioxide
hydrate (RuO2 H2O). The pH was raised to 12 and the
temperature to 40C. With rapid stirriny, 330.5 g of
12.1~ NaOCl (0.5 mole + 7.5% excess) in water was added
dropwise over about 1~2 hour while the temperature was
maintained at 40C with an ice bath. When the addition
was complete the ice bath was removed and the solution
was stirred for one hour, then filtered to remove catalyst
to give 879 g of a 7.5% aqueous solution of 3,3-dimethyl-
2-oxobutyric acid ("keto acid") as the sodium salt;
approximate yield 100%.
(b) At the end of ,the oxidation the Ru catalyst was in
the form of the black, water-insoluble ruthenium dioxide
hydrate. It was removed by filtration employing Celite
filter aid. The wet filter cake of catalyst plus filter
aid was added directly into a furtherbatch of hydroxy
acid salt solution and another oxidation conducted as
before by addition of hypochlorite.
(c) To 956 g of a 15.8% thiocarbohydrazide solution in
dilute HCl at 70 there were added over a 10-minute period
2682 g of 7.27% keko acid filtrate produced as in (a)
(temperature = 70C) with rapid stirring. After heating at
70C (pH 1.3) for 4 hours the solution was cooled to room
temperature and filkered. The solid was washed with water
and air dried to give 272.2 g of 99.3% pure 4-amino-6-tert.-
butyl-3-mercapto-1,2,4-triazin-5-(4-H)-one.
,
~$~
xample 2
A 1 liter 4-neck round bot~om ~lask equipped ~7itl~
a stirrer, thermometer, ancI addltion funIlel was charge~
with 524 g of aqueous solution containing 0.5 mole of
"hydroxy acid" and 100 mg oE ruthenium dioxide hydrate.
The temperature was held at 15C with an ice bath and
stirred while 294 g of 11.9% NaCCl solution was added
dropwise over abou~ 1.5 hours. The solution was then
stirred for one hour while it was allowed to come to
room temperature. Filtration through GI~A glass fiber
filter paper and washing the RuO2 with a small amount oE
dilute caustic gave 829 g of 7.25% keto acid. Notwith-
standing the low temperature and small amount of catalyst,
the yield was 94.4%.
; 15 Exam~le 3
The reaction was run as Example l except that the
temperature was Icept at 80C. Thus, 427.4 g (3.5%
ex,cess) of 9.0~/~ NaOCl was added over about l/2 hour to
555 g of 11.7% "hydroxy acid" containing 0.4 ~ of
Ru2.H2O. Filtration gave 982 g of product containing
5.82% "keto acid" (87.9%), 0.44% unreacted "hydroxy acid"
(6.5%), and 0.32% (6.6% yield) oE pivalic acid, as salt.
Thus, the higher temperature results in small amounts of
undesired pivalic acid by-product.
25 Examp 1 e 4
~ s in ~xample 1, the NaOCl was adcled at a constant
rate over 5 minutes while the temperature o.E the reaction
mixture was kept at 40C. This gave 982 ~, of product with
6.36% keto (96.1% yield) and no unreacted "hydroxy acid".
--6--
o . 3 g O r Ru2 . il~o was used. The lower tempera~ure
avoided pivali.c aci.d formation but the :Castcr ~-lddition,
compared with Example 1, resulted in a small clrop in
yield.
5 Example 5
Repeating Example 4 except that the NaOCl solution
was aclded over two hours, gave 9&3 g of product of which
6.55~o was "keto acid" (yield 99%).
Example 6
Example 1 was re-run using glass and platinum
; electrodes attached to a Sargent-Welch Model LS pH meter
and a 10 mv recorder. The NaOCl was added at a constant
rate with a metering pump. The potential of the solution
was kept at 330-400 mv. ~Jear the end of the reaction the
15 reading climbed up to 500 mv at which point the NaOCl
addition was stopped. There were obtained from 559 g of
11.8% hydroxy acid solution 921 g of 6.7% "keto acid",
yield 95%.
Example 7
To a mixture of 120 ml of water, 100 ml of 50%
sodium hydroxide solution, 1 g of Ru02. hydrate, and 0.5
mole of "hydroxy acid" (559.3 g of an ll. 8% sol.uLion) was
added chlorine gas at about 0.5 g/min. The temperature
was maintained at 0-5Cand when approxima~ely 0.7 moles
25 of C12 had been added the solution was allowed to warm to
room temperature and was filtered to give 839 g of product
containing 7.05% keto acid (91% yi.elcl) and 0.38% hydroxy
acid (4.8% yield).
., .
--7--
~$ ~ 3
Examplc 8
.
: As in Example 1 except ruthenium trichloride hy~rate
was used. 350.5 g of 1l.4% NaOCl was added dropwise to a
solution of 511.6 g o 12.9% hydroxy acicl containing 0.3 g
of RuC13:l~20. This gave 818.7 g of 7.25% keto acid
solution with a yield of 91.3%.
Example 9
As in Example 1 279.7 g of ].1.8% hydroxy acid was
charged to the flask and the pH was adjusted to 12. 0.3 g
of ~Uo2 H2o was added and 76.8 g of 26% NaOCl solution
was added dropwise. This gave 34l g of 9.53% ke~o acid
solution with a yield of 100Ø
It will be appreciated that the instant specification and
examples are set forth by way of illustration and not limitation,
15 and that various modifcations and changes may be made without
departing from the spirit and scope of the present invention.
