Note: Descriptions are shown in the official language in which they were submitted.
- 217976~
The isolation of hydroxy carboxylic acids from aqueous solutions
The present invention relates to a novel process for isolating
hydroxy carboxylic acids from their aqueous solutions.
Besides chemical syntheses, hydroxy carboxylic acids are
frequently also prepared by enzymatic processes. In this case,
the hydroxy carboxylic acids result in the form of dilute aqueous
10 solutions in the fermentation medium. A series of elaborate
enrichment processes is necessary in order to obtain the hydroxy
carboxylic acids, most of which have excellent solubility in
water, therefrom in pure or concentrated form.
It is not usually worthwhile to remove the water by direct
distillation or using a water-insoluble entrainer because of the
high energy input costs.
Because the hydroxy carboxylic acids have high solubility in
20 water, extraction with conventional solvents such as ethyl
acetate, methylene chloride or butanol is not particularly
efficient, and satisfactory results can be obtained only with
elaborate multiple extractions.
To solve this problem, reactive extractions have been proposed;
in these, water-insoluble higher secondary or tertiary amines
have been added to the organic extractor, and these form with the
hydroxy carboxylic acids the corresponding ammonium salts whose
extractability is better.
Chem. Ing.-Techn. 58 (1986) 308-317 describes the possibility of
increasing the partition coefficient of salicylic acid in the
xylene/water system by a factor of 50 by adding a secondary amine
(LA-2).
Chem. Ing.-Techn. 63 (1991) 809-816 refers, for example, to the
reactive extraction of lactic acid using the tertiary amine
Alamin 336 (tri-n-(C8-C10)-amine).
40 However, the subsequent workup of the extract is industrially
difficult because separation of hydroxy carboxylic acids and
amines by distillation even under reduced pressure requires
relatively high temperatures at which the hydroxy carboxylic
acids decompose or undergo unwanted side reactions.
~ 2179768
In the case of enantiomerically pure hydroxy carboxylic acids
under these conditions there is often partial racemization of the
product, which sets limits on the application of this process.
DE 25 45 658 discloses that the carboxylic acids formic acid,
acetic acid, propionic acid and acrylic acid can be extracted
from their aqueous solutions satisfactorily with amides. However,
there is no reference in this document to whether this process
can also be used for carboxylic acids other than the four
10 indicated above.
It is an object of the present invention to provide a process for
isolating hydroxy carboxylic acids from their dilute aqueous
solutions which does not have the disadvantages described above.
We have found that this object is achieved by isolating hydroxy
carboxylic acids by extraction from their dilute aqueous
solutions and subsequent distillation of the extracts obtained in
this way when the extractant used is a secondary amide of the
20 general formula I
Rl C ~ R2
N ~
R3
where Rl is hydrogen, alkyl, cycloalkyl, aryl, aralkyl or
hydroxyalkyl groups and R2 and R3 are, independently of one
another, alkyl, cycloalkyl, aryl, aralkyl or hydroxyalkyl groups,
30 with the proviso that the total of the carbon atoms in Rl, R2 and
R3 is from 7 to 14.
Hydroxy carboxylic acids mean those organic acids which, besides
one or more suitable COOH groups, contain at least one hydroxyl
group. The process according to the invention can be applied, for
example, to mono-, di-, tri- and polyhydroxy carboxylic acids.
The process is particularly suitable for naturally occurring
hydroxy carboxylic acids such as glycolic acid, lactic acid,
malic acid, tartaric acid, citric acid, gluconic acid, mandelic
40 acid, serine, threonine and tyrosine.
The process is very particularly suitable for isolating lactic
acid, in particular also enantiomerically pure lactic acid.
Concerning the radicals R2 and.R3 in the amides I, particularly
suitable compounds or mixtures thereof are derived from N-ethyl-
N-cyclohexylamine, N,N-dicyclohexylamine, N,N-dibutylamine,
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_
N-methyl-N-benzylamine, N-methylaniline, N-ethylaniline,
N,N-diamylamine, N-methyl-N-cyclohexylamine, N-n-butyl-N-cyclo-
hexylamine, N-methyl-N-2-heptylamine or N-propyl-N-cyclohexyl-
amine.
Concerning the radical Rl, formyl and lower alkyl or hydroxyalkyl
groups are preferred.
Since it is sometimes possible for transamidation of the amide I
10 with the hydroxy carboxylic acid to occur, it may be advantagéous
to choose as radical Rl in the amide the same radical as the
hydroxy carboxylic acid 80 that any transamidation occurring has
no adverse effect on the product.
Amides I which are preferably used are those in which the total
number of carbon atoms in the radicals Rl, R2 and R3 is less than
or equal to 10.
The amides of the formula I either are known or can easily be
20 obtained by known methods. As a rule, the amides I are used
without other solvents because the effectiveness of the
extraction is maximized in this way. If, however, an extraction
is to be carried out at relatively low temperature, ie. below the
solidification point of the amide I, it is advisable to add an
organic solvent which brings about a reduction in the
solidification point.
A measure of the suitability of the extractants is the partition
coefficient, which indicates the concentration of the hydroxy
30 carboxylic acid in the extractant in relation to the
concentration of the hydroxy carboxylic acid in water.
The complexity of the apparatu~ needed for the extraction
increases as this value decreases.
The partition coefficient for water is not so crucial in the
process according to the invention because the water dissolved in
the extract can easily be removed, together with the extractant,
from the hydroxy carboxylic acid by distillation.
The amount of extractant required depends on various parameters,
including the temperature, the amount and concentration of the
hydroxy carboxylic acid, the number of separation stages and
other characteristics of the apparatus and is familiar to the
skilled worker or can easily be determined by him.
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A temperature range from 0C to 100C is suitable and preferred
for the extraction. Although the uptake capacity of the
extractant for the hydroxy carboxylic acid is greater at the
lower values in this range than at higher temperatures, on the
other hand the rate of phase separation is slower. The economic
optimum is, as a rule, at from 40C to 80C, and it can easily be
determined by a number of routine tests.
The fact that the partition coefficients are distinctly lower at
10 higher temperature than at low temperatures can be additionally
exploited by carrying out a temperature-change extraction.
This entails extracting the aqueous hydroxy carboxylic acid
solution with amide I at low temperature, eg. 20C to 40C, and
subjecting the extract phase to a back-extraction with water at
high temperature, eg. 60C to 80C.
The extraction can be carried out continuously or batchwise. In
industrial application, continuous extraction by the
20 countercurrent process is preferred.
It is possible if required further to increase the effectiveness
by using multistage extraction apparatus, for example batteries
of mixers and separators or packed columns, which are familiar in
principle to the skilled worker.
The essential feature of the present invention is not the
extraction technique, which is conventional, but is the nature of
the extractant.
After the extraction step, the extracted phase is separated in a
manner familiar to the skilled worker into hydroxy carboxylic
acid and extractant and, where appropriate, water by
distillation. The result of the overall process is the hydroxy
carboxylic acid in pure form or, alternatively, as concentrated
solution.
The process according to the invention can be applied to the
isolation of hydroxy carboxylic acids which have been prepared
40 chemically or biotechnologically and are in the form of aqueous
solutions. It is also suitable furthermore for waste water
purification if the aim is to remove hydroxy carboxylic acid. It
is particularly suitable for isolating hydroxy carboxylic acid
from fermentation broths.
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The process according to the invention makes considerable savings
possible in energy and capital costs, both by comparison with
other extraction processes and by comparison with fractionation
by distillation.
The following examples serve to illustrate the invention further.
Example 1
10 Since the suitability of the extractants depends essentially on
the partition coefficients
Concentration of the acid in the organic phase
K =
Concentration of the acid in the aqueous phase
this coefficient was determined as follows:
50 g of a 7 ~ strength aqueous solution of the appropriate
hydroxy carboxylic acid were stirred with 50 g of extractant at
20 40C until equilibrium was reached. The stirrer was then switched
off and the mixture was left until the organic and aqueous phases
had clearly separated.
The partition coefficient was formed from the acid concentration
which was determined by titration.
The following table summarizes the partition coefficients of some
extractants according to the invention and compares them with
conventional ones:
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Extractant Acid K at 40C
N,N-Dibutylformamide Lactic acid 1.37
" Malic acid 1.36
" Citric acid 2.07
N,N-Dibutylacetamide Lactic acid 1.52
N,N-Dipropylpropionamide ~ 1.23
N,N-Dibutylpropionamide " 1.00
N,N-Di-n-butyllactamide ~ 0.65
Conventional extractants
Benzene Lactic acid ~ 0.01
Ethyl acetate " 0.29
Chloroform " 0.01
i-Butanol " 0.84
i-Butanol Citric acid 0.52
20 Example 2
This example shows the temperature dependence of the K value for
lactic acid in the N,N-di-n-butylformamide/water system.
The procedure for determining the K value was as indicated in
Example 1.
Temperature in C R value
1.37
1.24
1.15
Example 3
This example shows the concentration dependence of the K value of
citric acid at 40C in the N,N-di-n-butylformamide/water system.
40 The procedure for determining the X value was as indicated in
Example 1.
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Equilibrium concentration of K Yalue
citric acid in water at 40C
in percent by weight
0.5 2.70
1.1 2.47
2.5 2.07
