PROCESS FOR PREPARING AMINO ACIDS USING THE AMIDOCARBONYLATION REACTION
The present invention relates to a sequence for the
preparation of amino acids, for example alpha-amino acids,
in particular methionine, by making use of an
amidocarbonylation reaction. During the process, an N-acyl
amino acid is synthesised in an amidocarbonylation reaction
by making use of a catalyst, and this N-acyl amino acid is
then subsequently hydrolysed to the desired amino acid
while the carboxylic acid thereby formed is reconverted to
the corresponding carboxylic acid amide by reaction with
ammonia, followed by dehydration. This carboxylic acid
amide can then be re-introduced as a starting material in
the initial amidocarbonylation reaction step. According to
the invention, the catalyst used during the first reaction
step can be recovered and recycled into the first reactor
vessel. The synthesis can be conducted in a batch,
semi-batch or preferably in a continuous manner.
Amino acids are important products and are correspondingly
used in a variety of applications, such as human medicine,
the pharmaceuticals industry as well as in the synthesis of
a plurality of fine chemicals and active ingredients. In
particular they are used as additives in the fodder of many
livestock in enantiomerically pure form, but also in the
racemic form.
Several methods are employed on an industrial scale to
prepare amino acids, such as biotechnological processes, as
for example fermentation processes, and hydrolysis of
proteins. Chemical syntheses are also used for producing
amino acids. One possibility is the Strecker reaction or
its variants, such as the Bucherer-Bergs reaction. Still
further, the amidocarbonylation reaction is also known to
be used for preparing amino acids.

The amidocarbonylation reaction was discovered by, Wakamatsu
et al. in 1971 and is disclosed in the German patent
application DE-A-2115985. The reaction is catalysed by
various transition metal compounds and is a three component
reaction between a carboxylic acid amide, an aldehyde and
carbon monoxide, either in a pure form or as a mixture with
hydrogen (synthesis gas) (see Scheme 1).

Scheme 1
General Reaction Scheme according to the prior art
One should bear in mind that the utilisation of the
amidocarbonylation reaction is to be regarded as
advantageous in comparison to the conventional Strecker
synthesis of amino acids or its variants since the
amidocarbonylation requires carbon monoxide instead qf
hydrogen cyanide as one of its integral raw materials. This
is of considerable advantage due to the higher price and in
particular due to the high toxicity of hydrogen cyanide.
The products of the amidocarbonylation reaction are N-acyl
amino acids, having the general formula:

R1-CH (NH-CO-R2)COOH
R1 is: hydrogen, a linear, branched or cyclic alkyl
group that has from 1 to 10 carbon atoms,
especially 1 to 7, or
a linear or branched alkyl group that has from 1
to 10, especially 1 to 6 carbon atoms containing
a substituent(s) amido, amino, monoalkylamino,
dialkylamino, monoalkylamido, dialkylamido
alkoxy, alkylthio, hydroxy, thiol, carboxylic
acid or carboxylic acid alkyl ester group(s), or
a 1H-imidazole-, phenyl- or 3-indolyl-, p-
hydroxyphenyl or p-alkoxyphenyl residue, whereby
the said alkyl (alkoxy) group(s) has (have) 1 to
3 carbon atoms,
most preferred for R1 is a linear or branched
alkyl group that has from 1 to 10, especially 1
to 6 carbon atoms containing a substituent(s)
amido, alkoxy, alkylthio or a phenyl or p-
alkoxyphenyl residue, whereby the said alkyl
group(s) has 1 to 3 carbon atoms.
R2 is: hydrogen or a linear, branched or cyclic alkyl
group having 1 to 10 carbon atoms, or
a linear, branched or cyclic alkyl group having 1
to 10 carbon atoms, containing a substituent(s)
amido, monoalkylamido, dialkylamido hydroxy,
alkyoxy, thioalkoxy group(s)or
a substituted or non-substituted-aryrl-benzyl
group, where the substituent(s) may be a hydroxy,
alkoxy, fluoro, chloro, bromo or a trialkylamino
group, whereby the said alkyl group has 1 to 3
carbon atoms

The said N-acyl amino acids are starting materials
especially for the a-amino acids:
asparagine, aspartic acid, cystein, glutamine, glutamic
acid, histidine, serine, threonine, tryptophan, tyrosine,
most especially for alanine, glycine isoleucine, leucine,
methionine, phenylalanine, valine.
Substituted hydantoins can also be prepared instead of
N-acyl amino acids. In such a case, ureas are used as
starting materials, as for example disclosed in the
European patent application EP 1 048 656 A2.

The European patent application EP 338 330 Al and the
German patent application DE 19629717 also disclose the
synthesis of various N-acyl amino acids via the
amidocarbonylation reaction. DE 4415712 and DE 195456416
deal with that reaction as well, for example in the case of
the industrial preparation of sarcosinates.
However, no prior art suggests a process to prepare amino
acids, in particular methionine, comprising of the
amidocarbonylation reaction with convenient withdrawal of
the used catalyst, hydrolysis of the N-acyl amino acid
formed, and conversion of the by-product carboxylic acid
formed during the hydrolysis into a carboxylic acid amide.
With regard to this one should note that the aspect of
catalyst recycling of the expensive transition metal
catalyst used in the amidocarbonylation is also an
important target from an economic point of view, that is
avoiding the high costs involved in the acquisition of new
catalyst and the disposal of spent catalyst. Recycling of
the catalyst is furthermore advantageous with respect to
environmental reasons due to the often high toxicity of
transition metals and compounds related thereto.
A process for the recovery of cobalt carbonyl catalysts is
for example described in the European patent EP 779 102 B1.

According to that prior art, the active catalyst was
initially oxidised after the reaction to the more stable
cobalt(II) form, which was then extracted into aqueous
solution, precipitated as the hydroxide and subsequently
converted into a melt consisting of the hydroxide and N-
acyl amino derivative which can be used for regeneration of
the active catalyst under a synthesis gas atmosphere.
However, the same disadvantage as mentioned above occurs
according to that prior art. For example, handling problems
occur during the precipitation and drying of cobalt
hydroxide. Still further, if the process were to be run in
a continuous way, higher expenses would be incurred.
Summing up, the processes suggested in the prior art for
catalyst recovery during an amidocarbonylation reaction are
not suitable for the large scale industrial synthesis of
amino acids, especially methionine, due to the variety of
handling problems, occurring in particular for such amino
acids containing sulphur, as methionine.
There is, however, a strong need to find a way to recycle
the catalyst used during the synthesis of amino acids via
the amidocarbonylation. The carbonyl catalyst makes it
possible to make use of carbon monoxide as a starting
material, which is easier to handle and more widely
available than hydrogen cyanide. . ^
It is the object of the present invention to provide an
amidocarbonylation reaction for producing amino acids
providing a method of regenerating and recycling the
catalyst employed in the amidocarbonylation reaction to
increase the efficiency of the amidocarbonylation reaction
and to limit harmful emissj.gns- and environmental damage.
These objects have been solved by a process as disclosed in
the patent claims. The process is also suited for producing
sulphur containing amino acids, such as methionine, which

might be expected to cause problems with the transition metal catalyst.
Catalyst recycling means preferably regeneration of the catalyst, specifically
after removal of the product from the reaction mixture, and reuse of the
regenerated catalyst. According to an aspect of the invention, regeneration of
the catalyst from the reaction solution takes place by means of a chemical
conversion into an intermediate, from which the active catalyst can be later
regenerated, if necessary in a further separate step, and reused. According to
the invention the catalyst is separated, regenerated and subsequently reused.
In accordance with a preferred embodiment, the preparation of amino acids
occurs in a continuous manner. A particularly preferred process is directed to
the production of methionine.
According to the invention is provided a process for producing an amino acid
having the general formula
Ri-CH(NH-CO-R2)COOH (I)
wherein R1 is: hydrogen, a linear, branched or cyclic alkyl group that has from
1 to 10 carbon atoms, or a linear or branched alkyl group that has from 1 to
10, containing a substituent (s) amido, amino, monoalkylamino, dialkylamino,
monoalkylamido, dialkylamino alkoxy, alkylthio, hydroxy, thiol, carboxylic acid
or carboxylic acid alkyl ester group(s), or a 1H- imidazole-, phenyl- or 3~-indolyl-,
p-hydroxyphenyl or p-alkoxyphenyl residue, whereby the said alkyl (alkoxy)
group(s) has (have) 1 to 3 carbon atoms, R2 is: hydrogen or a linear, branched
or cyclic alkyl group having 1 to 10 carbon atoms, or a linear, branched or
cyclic alkyl group having 1 to 10 carbon atoms, containing a substituent(s)
amido, monoalkylamido, dialkylamido hydroxy, alkyoxy, thioalkoxy group(s) or
a substituted or non-substituted aryl or benzyl group, where the substituent(s)
may be a hydroxy, alkoxy, fluoro, chloro, bromo or a trialkylamino group,
whereby the said alkyl group has 1 to 3 carbon atoms said process comprising
the following reaction steps:

a) reacting an aldehyde RxCHO with an amide R2CONH2 in a molar ratio in a
range of 1:1 to 1:5 and carbon monoxide and hydrogen at a temperature
between 60° to 120°C as a heated reaction mixture in an amidocarbonylation
reaction to give an N-acyl amino acid in the presence of a cobalt carbonyl
catalyst, b) precipitating Co(N-acyl-amino acid)2 by feeding an oxygen containing
gas at a temperature between 60°C to 80°C into the reaction mixture after
completion of reaction a), and separating precipitated Co(N-acyl-amino acid)2,
and c) hydrolyzing the remaining dissolved N-acyl amino acid at a temperature
in the range of 120°C to 180°C to obtain the subsequent amino acid or a
trialkylamino group comprises the following steps:
a)Amidocarbonylation of an aldehyde with an carboxylic acid amide to give an N-
acyl amino acid in the presence of a Co-catalyst, carbon monoxide and
hydrogen,
b)feeding an oxygen containing gas into the heated reaction mixture after
completion of reaction.a) and conversion of the used catalyst to an intermediate
CofN-acyl-amino-acid)^, which precipitates from solution, preferably
regeneration of the catalyst from said intermediate by conversion with
synthesis gas to give said cobalt carbonyl catalyst;
c)hydrolysis of the N-acyl amino acid resulting from step a) to obtain the
subsequent amino acid, and

d) in a preferred case, conversion of the carboxylic acid '
resultf^ng from step c)" preferably with ammonia,
resultingXn the regenerationx.of_the-carboxyl.ic acid
amide used in\step a), while the catalyst used in step
a) is withdrawnXrom the reaction solution and
regenerated as shown in step b) and introduced into
the reaction medium ofsstep a) for another
amidocarbonylation reaction.
This overall process is illustrated in Figure 1 for the
preferred case of methionine synthesis. As apparent from
Figure 1, the raw materials required are an aldehyde, for
the case of methionine synthesis as demonstrated in Figure
1, 3-(methylthio)propanal, carbon monoxide and ammonia. The
ammonia is transported into the reaction in the form of
acetamide used in step a) and has the function of a
nitrogen carrier. Acetic acid formed during the hydrolysis
step is reconverted into acetamide by reaction with ammonia
and subsequent dehydration. •—— - - ~"" ~ j
The hydrolysis occurring during step c) is known to the
skilled person and is, fdr~exampl~e~discl\3s*ed~in~the~patent
application WO 02/14260. Details of the regeneration
reaction step of the amide can be taken from EP 919 539 Al.
In the first step the aldehyde and amide are mixed in a
solvent under an inert atmosphere. The molar ratio of the
aldehyde to the amide can be in the range of 1:1 to 1:5,
preferably in the range of 1:1 to 1:1.5.
A suitable and preferred solvent is dipolar and aprotic.
Examples of these are sulphones; dimethyl sulphoxide;
esters, like methyl acetate, ethyl acetate or butyl
acetate; ketones, like acetone or methylisobutylketone;
ethers, like tetrahydrofuran, dioxan, methyl tert-butyl
ether, diisopropyl ether; amides, like dimethyl acetamide,
DMF and .W-methylpyrrolidine, aromatics, like toluene;
nitriles, like acetonitrile and carboxylic acids.

The catalyst is preferably preformed in a separate reactor
vessel from the desired-cobalt"precursor with carbon
monoxide and hydrogen. Preferred amounts of the catalyst
are in the range of 0.1 mol% to 5 mol%, with respect to the
reacting aldehyde, particularly preferred in the range of 1
to 2 mol% carbonyl compounds of cobalt are used. The
presence of heteroatoms, especially sulphur, in the
starting aldehyde does not negatively influence the yield
of product, when cobalt is used as the metal in the
catalys t. ^ ■ — ,
The solution of the amide and the aldehyde is put into a
pressure resistant vessel and the vessel is pressurised
with synthesis gas.
The pressure of synthesis gas is set at 20 to 2 00 bar
(20,000 to 200,000 hPa), especially preferred are 80 to 130
bar (80,000 to 130,000 hPa).
Synthesis gas with H2/CO ratios of 1:1 to 1:9 can be used,
whereby the ratio of 1:8 to 1:9 is preferred. The pressure
is maintained constant during the reaction.
After pressurisation is completed, the vessel is heated to
a temperature in the range of 40 °C to 150 °C, preferably
between 60 °C and 120 °C, more preferred between 60 °C and
80 °C. ^-' —■ _
During the entire reaction period the reaction solution is
agitated, preferably by means of stirring, enabling a
maximal gas absorption into the solution.
According to a preferred embodiment of the process of the
present invention, a solution of the starting amide and the
catalyst are added to an organic solvent in a pressure
vessel. After pressurisation to the above mentioned
pressure and heating to the above mentioned temperature,
the aldehyde starting material is fed into the pressure
vessel by means of a pump at a constant linear or more

preferably non-linear rate during the reaction. In this way
the selectivity of the reaction can be increased, and the
amount of unwanted side products can be diminished.
After a reaction time of between 20 minutes and 6 hours,
or, if the process is run continuously, after an average
residency time of the same, the reaction solution is cooled
to 10 °C to 40 °C, preferably 20 °C to 30 °C. The synthesis
gas atmosphere is then released and the vessel is
subsequently re-pressurised to between 8 and 12 bar (8,000
to 12,000 hPa) with air. The solution is stirred at this
pressure. The dispersal of gas into the solution optimises
the yield. After approximately 2-3 hours, the volume of the
solution is preferably reduced by around 25 % in vacuo.
The remaining solution is then heated to preferably between
60 °C and 80 °C whilst having an oxygen containing gas,
especially air bubbled through it. Pink Co(J\T-acyl-amino
acid)2 precipitates and is withdrawn by filtration.
Conversion of separated Co (I\Facy 1 - amino acid) 2 into the
active carbonyl catalyst can then be accomplished using a
known procedure by heating a solution or slurry of
Co (JV-acyl-amino acid) 2 in a preferably polar aprotic
solvent under a synthesis gas atmosphere (EP-B-0 946 298) .
The filtrate obtained after removal of Co(W-acyl-amino
acid)2 is then cooled to preferably between 5°C to 20°C and
after a suitable amount of time the crystalline product, N-
acyl amino acid, can be isolated by filtration.
After removal of the last traces of organic solvent by
means of drying, the product 2\T-acyl amino acid is
transferred to a pressure resistance reaction vessel
containing water. The concentration of the J\T-acyl amino
acid in the water is in the range of 0.1 molar to 5 molar.
The reaction solution is then heated to a temperature in
the range of from 120 °C to 180 °C, preferably between

140 °C and 160 °C. Further details of such a hydrolysis
process are known by the skilled-person"and are, for
example, described in WO 02/14260. After an average
residence time of between 4 to 6 hours the solution is
cooled to a temperature in the range of from 10 °C to 40 °C
where upon the product amino acid precipitates. After
filtration and drying, the desired product amino acid is
obtained. __ ~- —~ - -- -
In a preferred embodiment of the invention the filtrate
containing the carboxylic acid formed during the
hydrolysis, as well as trace amounts of the starting .W-acyl
amino acids, is mixed with an organic solvent immiscible
with water in a counter flow extraction column. Preferred
organic solvents are cyclohexanone, butanone, ethyl acetate
and MIBK, particularly<>^eferred-is-MIBK**(methyr"isbbutyl
ketone). The carboxylic acid is transferred into the
organic layer and the aqueous solution containing
impurities and the remaining starting material is returned
to the hydrolysis reaction vessel. A part of the said
solution is also discarded in the form of a purge, in order •
to prevent the build-up of unwanted side products. The
organic solvent cofitaining the carboxylic acid (in
particular acetic acid) is then fed into a second counter
'"£low extraction column, where an aqueous solution of
"ammonia is used as the counter flow. The reaction leads to
the formation of an ammonium carboxylate in the aqueous
phase which is subjected to a dehydration reaction to
obtain a carboxylic acid amide. Details are known to the
skilled person, or for example described in EP 919 539 Al.
The organic solvent from the organic layer is separated and
after drying recycled in the first extraction column.
The single processes__are preferably conducted as connected
processes, which is an advantage during large scale
production.

The following examples are intended to illustrate the
invention, without having a limiting effect.
Examples
Example 1
3.02 g acetamide, 5.36 g 3-(methyl thio)propanal (97 %
purity) and 0.342 g of Co2(CO)8, the cobalt catalyst
precursor were dissolved in 50 ml butyl acetate in a 100 ml
laboratory autoclave. The reactor was pressurised to 130
bar (130,000 hPa) with 1:1 H2/CO synthesis gas and heated
to 70 °C whilst stirring. The reaction was stirred for 8
hours after which the reactor vessel was cooled to room
temperature and the pressure released. Analysis of the
reaction mixture using HPLC gave:
MMP conversion 100 %
Yield (I\T-acetyl methionine) 92.2 %
Selectivity (W-acetyl methionine) 92.2 %
Side products included approximately 5 %
1,3-bis (methylthio)propane.
The product W-acetyl methionine was recovered by filtration
of the product solution. Washing the solid with chilled
ethyl acetate and drying in vacuum gave N-acetyl methionine
as a white solid.
Example 2
3.02 g of acetamide and 0.142 g of Co2(CO)8, the cobalt
catalyst precursor, were dissolved in 20 ml of ethyl
acetate in a 100 ml laboratory autoclave. The reactor was
pressurised to 130 bar (130,000 hPa) with 1:1 H2/CO
synthesis gas and heated to 80° C whilst stirring. After 5
minutes a solution of 5.36 g MMP (97 %) in 25 ml of ethyl
acetate was slowly added using an HPLC pump at a rate of
0.42 ml/min up to 50 % addition, 0.21 ml/min up to 75 %
addition, 0.13 ml/min up to 91 % addition and 0.08 ml/min

up to 100 % addition. Subsequently, 5 ml of ethyl acetate
were added to the reaction in order to rinse the pump and
addition line. The reaction was continued for a further 2.5
hours, after which the reactor vessel was cooled to room
temperature and the pressure released. Analysis of the
reaction mixture using HPLC gave:
MMP conversion 96 %
Yield (W-acetyl methionine) 89.9 %
Selectivity (J)7-acetyl methionine) 93.6 %
Side products included < 1 % Itf-acetyl methionine ethyl
ester and approximately 4 % 1,3-bis(methylthio)propane.
Example 3
Itf-Acetyl methionine formed according to example 1 was
hydrolysed to methionine and the acetic acid formed reacted
with ammonia to form acetamide.
6.40 g of Itf-acetyl methionine were dissolved in 50.4 g of
water. The solution was transferred to a 100 ml pressure
vessel and heated to 165 °C whilst stirring for 5 hours,
during which the pressure remained constant at about 9 bar
(9,000 hPa).
After cooling to room temperature, the solution was
filtered and the recovered methionine was dried in vacuum.
N-Acetyl methionine conversion 93 %
Yield (methionine) 90 % (60 % isolated)
Yield (acetic acid) 92 %
The presence of the dipeptide Met-Met as well as the
diketopiperazine formed from two methionine molecules were
detected in HPLC (> 0.5 % overall).
The filtrate containing the acetic acid formed during the
hydrolysis, as well as trace amounts of the starting W-acyl

amino acids, is mixed with MIBK in a counter flow
extraction column.
The acetic acid is transferred into the organic layer and
the aqueous solution containing impurities and the
remaining starting material is returned to the hydrolysis
reaction vessel. A part of the said solution is also
discarded in the form of a purge, in order to prevent the
build-up of unwanted side products. The organic layer
containing the acetic acid is then fed into a second
counter flow extraction column, where an aqueous solution
of ammonia is used as the counter flow. The reaction leads
to the formation of an ammonium carboxylate which is
subjected to a dehydration reaction for obtaining acetamide
as described in EP 919 539 Al. The MIBK is then removed and
after drying recycled in the first extractor column.
Example 4
Production of methionine and removal of the used catalyst
by forming Co(iV-Acyl amino acid) 2
261 g of MMP (99 % pure), 151 g of acetamide and 17.1 g of
CO2(C0)s were dissolved in 2.5 1 of ethyl acetate in a 5 1
pressure vessel. The reactor vessel was then heated to 80
°C and pressurised to 130 bar of synthesis gas (ratio of
CO/H2 1:1) and the reaction mixture was stirred for 5
hours. After cooling to room temperature, the synthesis gas
pressure in the reactor was released and the reactor re-
pressurised with 10 bar (10,000 hPa) of air and stirred for
several hours. After removal of the reaction solution from
the pressure vessel and subsequent concentration of the
reaction solution to approximately 75 %, the remaining
solution was heated to 80 °C and air was bubbled through
this solution at a rate of 21 ml /s until the solution did
not change optically any more. The hot solution was
filtered and the pink precipitate of Co(J\7'-Ac-Met)2 washed
with warm ethyl acetate. The filtrate portions are combined

and cooled to 5 °C, whereupon the product W-acetyl
methionine crystallises out and can be isolated by
filtration and hydrolysed to obtain methionine.
Yield of Co(N-Ac-Met)2 90%
Total yield of N-acetyl methionine 80.7%

WE CLAIM:
1. Process for producing an amino acid having the general formula
R1-CH(NH-CO-R2)COOH (I)
wherein
R1 is: hydrogen, a linear, branched or cyclic alkyl group that has from 1
to 10 carbon atoms, or
a linear or branched alkyl group that has from 1 to 10,
containing a
substituent (s),amido, amino,
monoalkylamino, dialkylamino,
monoalkylamido, dialkylamino alkoxy, alkylthio, hydroxy, thiol,
carboxylic acid or carboxylic acid alkyl ester group(s), or a 1H-
imidazole-, phenyl- or 3-indolyl-, p-hydroxyphenyl or p-
alkoxyphenyl residue, whereby the said alkyl (alkoxy) group(s) has
(have) 1 to 3 carbon atoms,
R2 is: hydrogen or a linear, branched or cyclic alkyl group having 1 to 10
carbon atoms, or
a linear, branched or cyclic alkyl group having 1 to 10 carbon
atoms, containing a substituent(s) amido, monoalkylamido,
dialkylamido hydroxy, alkyoxy, thioalkoxy group(s) or

a substituted or non-substituted aryl or benzyl group, where the
substituent(s) may be a hydroxy, alkoxy, fluoro, chloro, bromo or a
trialkylamino group, whereby the said alkyl group has 1 to 3
carbon atoms
said process co'mprising the following reaction steps:
a) reacting an aldehyde R1CHO with an amide R2CONH2 in a
molar ratio in a range of 1:1 to 1:5 and carbon monoxide and
hydrogen at a temperature between 60° to 120°C as a heated
reaction 'mixture in an amidocarbonylation reaction to give
an N-acyl amino acid in the presence of a cobalt carbonyl
catalyst,
b) precipitating Co(N-acyl-amino acid)2 by feeding an oxygen
containing gas at a temperature between 60°C to 80°C into
the reaction mixture after completion of reaction a), and
separating precipitated Co(N-acyl-amino acid)2, and
c) hydrolyzing the remaining dissolved N-acyl amino acid at a
temperature in the range of 120°C to 180°C to obtain the
subsequent amino acid or a trialkylamino group.

2. The process as claimed in claim 1, wherein R1 is a linear, branched or
cyclic alkyl of 1 to 7 carbons or a linear or branched alkyl of 1 to 6
carbons.
3. The process as claimed in claims 1 and 2, whereby the filtrate
obtained after removal of Co (N-acyl-aminoacid)2 is then cooled to a range
between 5°C to 20°C, the crystalline, N-acyl amino acid, is isolated by
filtration and after removal of the last traces of organic solvent by means
of drying, the product N-acyl amino acid is transferred to a pressure
resistance reaction vessel containing water for hydrolysis.
4. The process as caimed in claim 1, comprising the reaction step to
regenerate the catalyst, whereby said Co(N-acyl amino acid)2 is
a) slurried or dissolved in an appropriate solvent,
b) heated under a synthesis gas atmosphere, and
c) the regenerated Co-carbonyl catalyst is fed to the amidocarbonylation
reaction.
5. The process as claimed in claims 1, comprising the reaction step to
regenerate the amide used in step a), of claim 1 whereby

a) after separation of the amino acid carboxylic acid formed by hydrolysis
is extracted and transferred into the organic layer which is brought into
contact with aqueous ammonia,
b) a ammonium carboxylate is fomed in the aqueous phase,
c) said carboxylate is subjected to a dehydration reaction for obtaining
carboxylic acid amide, and
d) said amide is fed to the amidocarbonylation process.

6. The process as claimed in one or more of the proceeding claims,
wherein methionine is produced from 3-(methylthio)propanal by
amidocarbonylation.
7. The process as claimed in one or more of the proceeding claims,
wherein the process is conducted in a conducted in a continuous
manner.

ABSTRACT

TITLE: PROCESS FOR PRODUCING AN AMINO ACID
Process for producing an amino acid having the general formula
R1-CH(NH-CO-R2)COOH (I)
wherein R1 is: hydrogen, a linear, branched or cyclic alkyl group that has
from 1 to 10 carbon atoms, or a linear or branched alkyl group that has
from 1 to 10, containing a substituent (s) amido, amino,
monoalkylamino, dialkylamino, monoalkylamido, dialkylamino alkoxy,
alkylthio, hydroxy, thiol, carboxylic acid or carboxylic acid alkyl ester
group(s), or a 1H-imidazole-, phenyl- or 3-indolyl-, p-hydroxyphenyl or p-
alkoxyphenyl residue, whereby the said alkyl (alkoxy) group(s) has (have)
1 to 3 carbon atoms, R2 is: hydrogen or a linear, branched or cyclic alkyl
group having 1 to 10 carbon atoms, or a linear, branched or cyclic alkyl
group having 1 to 10 carbon atoms, containing a substituent(s) amido,
monoalkylamido, dialkylamido hydroxy, alkyoxy, thioalkoxy group(s) or
a substituted or non-substituted aryl or benzyl group, where the
substituent(s) may be a hydroxy, alkoxy, fluoro, chloro, bromo or a
trialkylamino group, whereby the said alkyl group has 1 to 3 carbon
atoms said process comprising the following reaction steps: a) reacting
an aldehyde R1CHO with an amide R2CONH2 in a molar ratio in a range
of 1:1 to 1:5 and carbon monoxide and hydrogen at a temperature
between 60° to 120°C as a heated reaction mixture in an

amidocarbonylation reaction to give an N-acyl amino acid in the presence
of a cobalt carbonyl catalyst, b) precipitating Co(N-acyl-amino acid)2 by
feeding an oxygen containing gas at a temperature between 60°C to 80°C
into the reaction mixture after completion of reaction a), and separating
precipitated Co(N-acyl-amino acid)2, and c) hydrolyzing the remaining
dissolved N-acyl amino acid at a temperature in the range of 120°C to
180°C to obtain the subsequent amino acid or a trialkylamino group.