Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
~75~57
BAC~G~OUND O'F THE;I~V~TION
1. Field Of The Invention
. ~
This invention relates to certain new compounds
which are useful for the production of tetronic acid~ This
inven~ion also relates to a proces's of preparing such new
compounds.
2. Pr~or Art
Tetronic acid~,~hich is used among other things
as an accelerator for photo:graphic development, is known to
be produced from 4-mono-haloacetoacetic ester or acid.
According to the Swiss Patent N~. 503,'722,,4-chIoroaceto-
acetic ester is reacted With an aromatic amine to produce
3-arylaminocrotolactone,,and the'tetronic acid is liberated
from such lactone by means o~ ~ mineral acid. The disad-
vantage o~ such method is that the isolation of the
tetxonic acid only can be realized by means o high vacuum
subli~ation. Accordin~ to Swiss Patent No. 529,128,
4-haloacetoacetic acid is reacted with an alkali in an
~queous solution. By treatment wit~'a mineral acid the
tetronic acid is liberated. Here too the isolation of the
tetronic acid must be accomplished by means of high vacuum
sublimation; moreoVer, the achieved yield is only 43 to 44
percent.
~L
~4
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BR{OAD DESCRIPTION OE~ T~ INVENTION
An object of the invention is to provide 4-hydroxy-
acetoacetic acid alkyl esters, especially 4-hydroxyaceto-
acetic acid methyl ester and 4-hydroxyacetoacetic acid
ethyl ester, which can be used Eor the production of
tetronic acid, among other things. Another object o~ the
invention is to provide a process for prepariny such
4-hydroxyacetoacetic acid alkyl esters. Other objects and
advantages of this invention are set out herein or are
obvious to one ordinarily skilled in the art.
The objects and advantages o~ this invention are
achieved by the process and compound of this invention.
The invention in~olves a process for preparing
a 4-hydroxyacetoacetic acid alkyl ester. The process starts
out from 4-haloaceto~cetic acid alkyl ester to produce the
such new compounds by way of 4-benzyloxyacetoacetic acid
alkyl ester by means o~ hydro~enolysis. The process
includes converting a 4-haloacetoacetic acid alkyl ester
into the corres,ponding ~-benzyloxyacetoacetic acid alkyl
ester and hy~enolyzing the'latter into the corresponding
4-hydroxyacetoacetic acid alkyl ester. The hydrogenolysis
is preferably carried out under pressure and in the presence
o~ a hydrogenation catalyst.
In a preferred met~od of production, 4-haloaceto-
acetic ester is converted with an alkali metal salt of
ben,zyl alcohol at a temperature of O to 40C. in an
organic solvent, prefexably dimethyl sulfoxide or tetra-
hydrofuran,and the 4-benzyloxyacetoacetic acid alkyl ester
obtained thereby is hydrogenolyzed.
5~7
The invention includes 4-hydroxyacetoacetic acid alkyl
esters, which preferably are 4-hydroxyacetoacetic acid
methyl ester or 4-hydroxyacetoacetic acid ethyl ester.
The invention also includes the composition composed
of a 4-haloacetoacetic acid alkyl ester, an alkali metal
salt of benzyl alcohol and an organic solvent. Preferably
the alkyl estex of the 4-haloacetoacetic acid alkyl ester
has 1 to 4 carbon atoms, and the organic solven-t is
dimethyl sulfoxide or tetrahydrofuran. T~e invention further
includes the composition composed of a 4-benzyloxyacetoacetic
acid alkyl ester, hydrogen, a solvent and a hydrogenation
catalyst.
DETAILED DESCRIPTION OF THIS INVENTION
As used herein, all parts, ratios~ percentages and
proportions are on a weight basis, unless otherwise stated
herein or otherwise obvious herefrom to one ordinarily
skilled in the art.
Examples of the 4-haloacetoacetic ester are the
bromo- and chloro-derivatives. Preferably~ the 4-halo-
acetoacetic acid alkyl ester is a 4-chloroacetoacetic acid
alkyl ester, especially the methyl and e~hyl esters.
Examples of the alkali salts of benzyl alcohol are
the potassium or sodium salts - preferably the sodium salt
is used. The sQdium sa-t of benzyl alcohol is produced
preferably from sodium hydride and benzyl alcohol in an
organic solyent. The reaction temperature in the conversion
step e~fectively is O to 40C.
Hydrogenolysis is the cleavage of a bond in an
organic compound with the simultaneous addition of a
hydrogen atom to each fragment (by hydrogenolysis one
understands the decomposition o~ a compound with concurrent
hydrogenation). Hv~ro~enolysis is the combination of hydrogen
with another substc~nce, usually an unsaturated organic
~ompound, and usually under the influence of temperature,
pressure, and catalysts (usually nickeI). The hydrogeno-
lysis reaction is carried out effectively in the invention
under a pressure of 1 to 8 atm. Pre~erably, the hydrogena~
tion treatment is carried out in the presence o~ a hydro-
generation catalyst, such as, a noble metal. Examples
of the noble metals are gold, silver, platinum, palladium,
iridium, rhodium, xuthenium, osmium, cobalt, Raney-
--5--
l~S~
nickel and others. In order to increase the reactionsurface, such catalysts are applied effectively to carriers,
for example, pumice stone, coal, silica gel, alumina and
others.
Tetronic acid is 2,4-dioxo-tetrahydrofuran or
~ -ketobutyrolactone. Tetronic acid is useful as an
accelerator for photographic development.
By way of summary, 4-hydroxyacetoacetic acid alkyl
ester is obtained by the hydrogenolysis of the 4-benzyl-
oxoacetoacetic acid alkyl ester.
EXAMPLE 1
7.56 g o~ 80 percent sodium hydride was freed of
white oil by washing three times with 30 ml of petroleum
ether (boiling point, 40 to 60C.) and was added to 160 ml
of tetrahydrofuran. Then 14.28 g of benzyl alcohol was
added in doses while stirring in such a way that a reaction
temperature of 40C. was maintained. After hydrogen
development was com~leted, a solution of 19.74 g (95.5
percent = 0.1145 mole) of chloroacetoacetic ester in 80 ml
of tetrahy~rofuran was addçd during 1 hour drop by drop,
whereby a temperature of 40C. prevailed. After 15 hours of
stirring, whereby the temperature dropped to ambient
temperature, half of the tetrahydrofuran was evaporated
on a vacuum rotation evaporator. The still-flowable residue
was poured in the form of a thin jet into a mixture of 14.3 g
of concentrated HCl in 150 g of ice water, whereby the pH
adjusted itself to S after completion of the addition. Then
the residue was extracted four times with ether and~ after
washing and drying, the ether was evaporated on the vacuum
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rotation evaporator. The residue was distilled. 22.52 g
(83.2 percent) of 4-benzyloxyacetoacetic acid e~hyl e~ter
~Kpo 4 126C.) resulted.
21.24 g of sUch ester, dissolved in acetic ester
(100 ml), was inserted into a 200 rnl steel autoclave provided
with a magnetic st:irrer and was hydrogenolized at a pressure
of 5 atm in the presence of 1.05 g of Pd 5 percent on coal
with hydrogen. A~ter the reaction concluded, which amounted
to about 2 hours, and after a 2 hour period after the reaction
10 time ended, the catalyst ~as filtered off and the filtrate
was evaporated at 35C. on the vacuum rotation evaporator.
The residue was dried in under high vacuum. 13.4 y of
4-hydroxyacetoacetic acid ethyl ester resulted in the form
o a slightly yellowish oil.
Elemental analysis (C6Hl0O4/ MG 146.14)
Found: C 49.7 percent i 0.1 H 7~1 percen-t + 0.1
Theory: C 49.3 percent H 6.9 percent
IR (thin film)
Bands at 3480 (vs), 2950 (m), 1745 (vs), 1725 ~vs),
1325 (m) and 1030 (m) cm 1
NMR (10 percent in GDC13)
- 1.30 (t, 3H) ~ = 3.52 (s, 2H)
S= 4.27 (q)
-- ~4H)
J - 4.10 (s)
OH at ~ = 3.2 to 3.7 ppm
MS: M 164, M/e 1-5, 101, 88
~75(3S~
EX~MPL~ 2
22.68 g of 80 percent sodium hydride was washed
with petroleum ether analogously to Example 1 and was
added to 460 ml of tetrahydrofuran. While stirring, 42.84 g
of benzyl alcohol was added drop by drop within 45 minutes
at 20 to 32C. A~ter the H2 development had stopped,
54.2 g (97.5 percent = 0.35 mole) of 4-chloroacetoacetic
acid methyl ester was added drop by drop within 45 minutes
at 20 to 30C. The light-brown suspension was tnen stirred
for 4 hours at about 20C. and subsequently it was poured
into a solution of 92.9 g of concentra~ed hydrochloric acid
in 400 ml of water. The light-brown mixture was extracted
with three portions of e~her, each of 150 ml, and the
extracts were combined. The combined extract was washed
twice, each time with 100 ml of saturated NaCl solution.
The ether phase was dried over Na2S04, was fi]tered and was
eyaporated in a xotation eyaporator at 30 to 40C. The
residue was distilled and 45.1 g (58.1 percent) of 4-benzyl-
o~yacetoacetic acid methyl este~ (~p 1 mm = 126 to 129C.)
resulted.
IR (thin film)
B~nds at 1752 (vs), 1730~(vs), 1325 (m~, ~nd
1100 (m) cms~
NMR (DMSO-d6)
- 7.32 (m, 5H~
~ = 4.51 (s, 2H)
J ~ 4.25 (s, 2H)
_ 3.62 (s, 3~)
= 3.60 (s, 2H)
--8--
ll~S~S~
22.22 g of such ester, dissolved in 100 ml of
acetic ester, w~s put into a 200 ml steel autoclave provided
with a magnetic stirrer and was hydrogenolyzed in the
presence of 1.1 g of Pd 5 percent on coal with water at a
pressure of 5 ba~. A~te~ the reaction, the catalyst was
filtered off and the filtrate was evaporated in the rotation
eyaporator at 30 to.35C. The light-brown residue
continued to be dried for another hour in the high vacuum.
As a product, 13.3 g o~ 4-hydroxyacetoacetic acid methyl
ester was obtained in the form of a yellow liquid.
IR (thin ~:i;lm)
Bands at 3460 (m), 1750 (vs), 1730 (vs), 1440 (m),
1330 (m), 1270 (m) and 1060 (m) cms
NM~ (D~SO-;d6)
Jr= 5.00 (wide, l~H)
= 4.10 (s, 2H)
= 3.60 (s, 3H)
~ - 3.54 (s, 2~)
EX~MPLE 3
4-Hydroxyacetoacetic acid alkyl ester can be
converted into tetronic acid, ~or example, by treating it
wit~ a mineralic acid at room temperature. Examples of such
mineral or inorganic acids is sul~uric acidl hydrochloric
acid (preferred) and phosphoric acid.
4.43 g of 4-hydroxyacetoacetic acid ethyl es~er was
treated with 10 ~1 18 percentic aqueous HCl over a 6-hour
period at a temperature between 18 and ~5C. Thereafter
the HCl was evaporated off at 30C. using a vacuum rotation
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evaporator. The crystals were washed with water. 3.0 g o~
tetronic acid having purity o~ 95.8 percent resu~ted.
--10--
