TW201329023A - Process for the preparation of racemic α -amino acids - Google Patents

Abstract

Process for the preparation of racemic α -amino acids or of glycine, wherein the corresponding α -hydroxycarboxylic acid, selected from hydroxyacetic acid, lactic acid, malic acid, α -hydroxyglutaric acid, isocitric acid, tartronic acid and tartaric acid, or at least one salt of the corresponding α -hydroxycarboxylic acid is reacted in the presence of at least one heterogeneous catalyst which comprises at least one transition metal, in the presence of hydrogen with at least one nitrogen compound (c), where the nitrogen compound (c) is selected from primary and secondary amines and ammonia.

Description

Method for preparing racemic α-amino acid

The present invention relates to a process for the preparation of racemic α-amino acid or glycine, which is selected from the group consisting of glycolic acid, lactic acid, malic acid, α-hydroxyglutaric acid, isocitric acid, hydroxymalonic acid and Corresponding α-hydroxycarboxylic acid of tartaric acid or at least one salt of the corresponding α-hydroxycarboxylic acid is reacted with at least one nitrogen compound (c) in the presence of hydrogen in the presence of at least one heterogeneous catalyst comprising at least one transition metal, The nitrogen compound (c) is selected from the group consisting of a primary amine and a secondary amine and ammonia.

Furthermore, the invention relates to mixtures of racemic alpha-amino acids with the corresponding alpha-hydroxycarboxylic acids.

Furthermore, the invention relates to the use of the mixtures according to the invention.

Amino acids have many fields of application. For example, L-amino acids are used in peptide synthesis and protein synthesis. However, racemic amino acids are also valuable intermediates.

The preparation of racemic amino acids by Strecker synthesis is known per se. Disadvantageously, in the case of hydrocyanic acid and/or the corresponding cyanide, extremely toxic substances are required which contribute to the need for special safety precautions.

US 2004/092725 discloses a process for the synthesis of alpha-amino acids from the corresponding alpha-hydroxycarboxylic acids by reaction with ammonia at elevated pressure and preferably at least 300 °C. However, the yield is low. For example, it was revealed that the yield of synthesis of glycine at 374 ° C was 4.3%, and the yield of synthesis of α-alanine at 374 ° C was 2.8%. however, This type of yield is unsatisfactory in industrial processes. In addition, most of the products obtained are darker in color and then require a complicated purification process.

Therefore, it is an object to provide a process by which an α-amino acid can be obtained in good yield. It is also an object to provide precursors for the production of a mixture of detergents and cleaning agents, including compositions for machine dishwashing, which tend to form clots with a low or no tendency to form clots.

Thus, it has been discovered that the methods defined in the text are also referred to as methods of the present invention within the context of the present invention.

For carrying out the process of the invention, the starting materials used are at least one alpha-hydroxycarboxylic acid, for example a mixture of two or three alpha-hydroxycarboxylic acids or an alpha-hydroxycarboxylic acid. The α-hydroxycarboxylic acid used may be in enantiomerically pure form or in the form of a mixture of enantiomers, for example in the form of a racemate, meaning that the enantiomers of the α-hydroxycarboxylic acids in question exist. body.

The alpha-hydroxycarboxylic acid used may be in the form of a free acid or a partially or fully neutralized form. If the α-hydroxycarboxylic acid is to be used in a completely or partially neutralized form, an ammonium salt and an alkali metal salt such as a potassium salt and especially a sodium salt are preferred.

Examples of the α-hydroxycarboxylic acid are glycolic acid, lactic acid (especially L-lactic acid), malic acid (especially L-malic acid), and α-hydroxyglutaric acid, and isocitric acid, hydroxymalonic acid, and tartaric acid. Particularly preferred examples are racemic lactic acid, (-)-lactic acid and (+)-lactic acid.

In the case of preparation of non-pivotic glycine, glycine is obtained without obtaining a racemate.

In one embodiment of the invention, the method of the invention is in an aqueous medium In progress. This is understood to mean that the alpha-hydroxycarboxylic acid or its salt is suspended or dissolved in water or contains at least 75% by volume of water and may comprise a total of up to 25% by volume of organic solvent (eg tetrahydrofuran or N,N-dimethylformamide) In the mixture, the volume % is based on the total continuous phase. Alcohol is not suitable as an organic solvent. It is preferred not to use an organic solvent or to use only 0.1 to 5% by volume of an organic solvent in a continuous phase.

In one embodiment of the invention, the process of the invention is carried out at a pH in the range of 4 to 14, preferably 6 to 14, and especially preferably 8 to 13.5.

According to the invention, it is reacted with at least one nitrogen compound (c), wherein the nitrogen compound (c) is selected from a primary amine, preferably a secondary amine and even more preferably ammonia. Examples of primary amines are specifically C ₁ -C ₁₀ alkylamines such as methylamine, ethylamine, isopropylamine, tert-butylamine, n-decylamine, and aromatic amines (such as aniline), C ₃ -C ₇ Cycloalkylamines (such as cyclohexylamine) and monoethanolamine. Examples of secondary amines are di-C ₁ -C ₁₀ alkylamines, in particular dimethylamine, diethylamine and diisopropylamine, and di-C ₂ -C ₄ -hydroxylalkylamines (specifically diethanolamine) And a mono C ₁ -C ₁₀ alkyl mono C ₂ -C ₄ hydroxyalkylalkylamine (such as N-methyl-N-ethanolamine), and a cyclic secondary amine (such as piperidine and morpholine). Other suitable nitrogen compounds (c) are iminodicarboxylic acids, in particular imidodiacetic acid.

In a preferred embodiment of the invention, the selected nitrogen compound (c) is ammonia, i.e., reacts with ammonia. Ammonia may be liquid ammonia, gaseous ammonia or aqueous ammonia ( "NH ₄ OH") form was added to the reaction mixture. If it is desired to add ammonia in the form of an ammonium salt, the ammonia is preferably added in combination with at least one strong base (for example in combination with NaOH or KOH). It is preferred to add ammonia in the form of liquid ammonia or ammonia.

In one embodiment, the alpha-hydroxycarboxylic acid and the nitrogen compound (c) are in a range of 1:1 to Mohr ratio in the range of 1:100, preferably in the range of 1:2 to 1:50, and particularly preferably in the range of 1:3 to 1:30. Here, the fraction of the nitrogen compound (c) means the sum of all the nitrogen compounds (c).

In one embodiment, the alpha-hydroxycarboxylic acid and the ammonia are in the range of from 1:1 to 1:100, preferably from 1:2 to 1:50, and more preferably from 1:3 to 1:30. Ear is better than use.

The method of the present invention is carried out at a hydrogen-based (i.e., H ₂₎ is present. In one embodiment of the invention, the process of the invention is carried out such that the molar ratio of alpha-hydroxycarboxylic acid to hydrogen is generally set in the range of from 1:1 to 1:90, preferably from 1:2 to 1:30. . In another embodiment, the molar ratio of alpha-hydroxycarboxylic acid to hydrogen is established in the range of 2:1 to 1.01:1.

In one embodiment of the invention, the hydrogen may be diluted by means of a gas which is inert under the reaction conditions of the process of the invention (for example with nitrogen or at least one inert gas, for example with argon).

The process of the invention is carried out in the presence of at least one heterogeneous catalyst comprising at least one transition metal. The heterogeneous catalyst herein may be: (i) a metal-containing catalyst supported on a solid support in the form of particulates, (ii) a metal-containing catalyst supported on a solid support in a non-particulate form, (iii) none Catalytically active particles of the support.

Within the context of the present invention, the term catalyst herein comprises a transition metal (which acts as a catalytically active species) ("primary metal") or, optionally, its precursor, and optionally a support and optionally doping.

By "solid support" it is to be understood herein to mean materials which are solid under the reaction conditions of the process of the invention and which are suitable for shaping heterogeneous catalysts.

"Present in the form of microparticles" is understood to mean that the support in question is in the form of particles having an average diameter in the range of from 0.1 μm to 2 mm, preferably from 0.001 to 1 mm, preferably from 0.005 to 0.5 mm, in particular. In the range of 0.01 to 0.25 mm.

"Presence in the form of non-particulates" is understood to mean that at least one dimension (width, height, depth) of the support is greater than 2 mm, preferably at least 5 mm, wherein at least one other dimension (eg one or two other dimensions) The size can be less than 2 mm, for example in the range of 0.1 μm to 2 mm. In another variation, the support present in non-particulate form has three dimensions, one dimension greater than 2 mm, preferably at least 5 mm. A suitable upper limit is, for example, 10 m, preferably 10 cm.

Examples of supports present in non-particulate form are metal meshes (such as steel mesh or nickel mesh), as well as wires (such as steel wires or nickel wires), and shaped articles such as beads, Raschig rings, strands. Line and spindle.

In one embodiment of the invention, the catalyst used is in the form of a shaped article, for example in the form of a lozenge or strand.

Examples of shaped articles which are particularly suitable for dimensions are ingots having dimensions of 6.3 mm, 3.3 mm, 2.2 mm and strands having a diameter in the range of 1.5 to 3 mm.

An example of a support present in the form of microparticles is a powder which may be free flowing or suspended.

Examples of materials from which supports can be produced in the form of particles are Al ₂ O ₃ , SiO ₂ , aluminosilicates, hydrotalcites, TiO ₂ , ZrO ₂ , activated carbon, especially Al ₂ O ₃ , ZrO ₂ and TiO. ₂ .

Examples of the unsupported catalytically active particles (iii) are Raney metals such as cupola, nickel and nickel. The unsupported catalytically active particles may be present, for example, in the form of a sponge or a framework catalyst.

In addition to the support and transition metal, the catalyst may also comprise one or more forming agents, such as graphite or stearic acid.

Examples of transition metals suitable for use as catalytically active materials ("primary metals") in metal-containing catalysts useful in the process of the present invention are transition metals of Groups 4 to 12 of the Periodic Table of the Elements, and more preferably elemental periods. The transition metals of the first period of Groups 4 to 12 of the table, that is, Ti to Zn, and the transition metals of Groups 8 to 11 of all periods of the periodic table. Particularly preferred transition metals are Co, Ni and Cu.

The transition metal in the catalyst used in the process of the invention may be doped, for example, via one or more other transition metals (such as Zr or Ti) or via Ca, Sn, Al or Na. Doping is understood here to mean a transition metal or a Na, Al or Ca incorporation of a transition metal or Na, Sn, Al or Ca in the range of 0.1 to 2 mol %, based on the main metal. However, in the present invention, the conventional incidental trace elements produced by the preparation of the main metal are considered to be excluded from the doping.

In one embodiment of the invention, the heterogeneous catalyst is selected from the group consisting of a Mooney metal and a transition metal applied to a solid support. Preferred transition metals (primary metals) are selected from the group consisting of Ni, Cu and Co.

In order to prepare a catalyst suitable for the process of the invention and to store it, it is customary to use the transition metal in the form of a precursor, ie in the form of a compound, for example in the form of an oxide, hydroxide or oxidehydroxide. Or in the form of an alloy, and prior to or in situ activation of the catalyst, the catalyst is preferably activated by reduction or by removal of at least one component of the alloy. Preferably, when the process of the invention is carried out, the transition metal is present in the heterogeneous catalyst in a zero oxidation state for at least a portion of the time.

In one embodiment of the invention, the catalyst is selected from the group consisting of materials in the form of microparticles, the mass of which, in each case determined before activation with hydrogen, comprises: a total of from 15 to 80% by weight, preferably from 30 to 70. % by weight, particularly preferably from 35 to 65% by weight, of the oxygen-containing compound of aluminum (calculated as Al ₂ O ₃ ), in the range of from 5 to 35% by weight, preferably from 10 to 30% by weight, particularly preferably 12 Up to 28% by weight, particularly preferably 15 to 25% by weight of nickel oxygenate (calculated as NiO), in total in the range of 5 to 35% by weight, preferably in the range of 10 to 30% by weight, particularly preferably Oxygenated compounds of cobalt (calculated as CoO) in the range of from 12 to 28% by weight, particularly preferably from 15 to 25% by weight, in total from 1 to 20% by weight, preferably from 2 to 18% by weight, particularly preferably 5 Up to 15% by weight of copper oxygenate (calculated as CuO), in total in the range of 0.2 to 5% by weight, preferably in the range of 0.4 to 4.0% by weight, particularly preferably in the range of 0.6 to 3.0% by weight, especially An oxygen-containing compound (calculated as SnO) in the range of 0.7 to 2.5% by weight.

In one embodiment of the invention, the catalyst is selected from the group consisting of materials in the form of microparticles, the mass of which, in each case determined before activation with hydrogen, comprises: 22 to 45% by weight, preferably 25 to 40% by weight of zirconium. Oxygenated compound (calculated as ZrO ₂ ), 1 to 30% by weight, preferably 2 to 25% by weight, particularly preferably 5 to 15% by weight, of copper oxygenate (calculated as CuO), 5 to 50% by weight, Preferably 15 to 45 wt%, particularly preferably 25 to 40 wt% of nickel oxygenate (calculated as NiO), 5 to 50 wt% of cobalt oxygenate (calculated as CoO), 0 to 10% by weight The weight of aluminum and/or manganese oxygen compounds (where zirconium (calculated as ZrO ₂ ) and aluminum and/or manganese (calculated as Al ₂ O ₃ and/or MnO ₂ ) is preferably at least 2.5), particularly preferably 0 % by weight of aluminum and/or manganese oxygenate, 0 to 5% by weight, preferably 0% by weight, of molybdenum oxygenate (calculated as MoO ₃ ).

In one embodiment of the invention, the catalyst is selected from the group consisting of particles in the form of microparticles, the mass of which, in each case determined before activation with hydrogen, comprises: 50 to 95% by weight, preferably 55 to 85% by weight. Particularly preferably 60 to 80% by weight of zirconium oxygenate (calculated as ZrO ₂ ), 5 to 50% by weight, preferably 15 to 45% by weight, particularly preferably 20 to 40% by weight of nickel oxygenate (according to NiO calculation).

In one embodiment of the invention, the molar ratio of nickel to copper is greater than 1, more preferably greater than 1.2, and most preferably in the range of 1.8 to 8.5.

Preferably, the catalytically active host of the catalyst used in the process of the present invention does not comprise ruthenium, osmium, iron and/or zinc, and is not in the form of a metal (oxidized state = 0) nor in the form of an ion (oxidized state ≠ 0). .

In one embodiment of the invention, the BET surface area of the catalyst suitable for the process of the invention is in the range of from 1 to 1000 m ² /g, preferably from 10 to 500 m ² /g, according to DIN 66131 by N ₂ adsorption measurement. .

It is possible to use different methods to prepare the preferred catalysts for the variations (i) and (ii) of the process of the invention. Suitable catalysts of variants (i) and (ii) can be obtained by, for example, kneading a powdery mixture of hydroxides, carbonates, oxides and/or other salts of the components with water and subsequently extruding and obtaining Block tempering (heat treatment).

The precipitation process is preferably used to prepare the catalysts of variants (i) and (ii) for use in the process of the invention. Therefore, preferred catalysts can be obtained by, for example, by means of a base, nickel, cobalt, copper and tin components in the presence of a slurry of slightly soluble aluminous, titanium, cerium and/or zirconium compounds (precipitates) The precipitate is co-precipitated from a brine solution containing these elements, and then washed, dried and calcined to obtain a precipitate. The slightly soluble aluminous, titanium, strontium and/or zirconium compounds which may be used are, for example, oxides, hydrated oxides, phosphates, borates and decanoates. A slurry of slightly soluble aluminum oxide, titanium, cerium and/or zirconium compound can be prepared by suspending fine particle powder of such a compound in water under vigorous stirring. Slurry of slightly soluble aluminous, titanium, cerium and/or zirconium compounds preferably by means of a base, by means of corresponding slightly soluble aluminous, titanium, cerium and zirconium compounds from aluminium, titanium, cerium and/or zirconium compounds It is prepared by precipitation in an aqueous solution.

Preferably, the catalysts of variants (i) and (ii) used in the process of the invention are prepared by coprecipitation (mixed precipitation) of all of its components. For this purpose, the brine solution containing the catalyst component is rapidly mixed with an aqueous solution of a base such as sodium carbonate, sodium hydroxide, potassium carbonate or potassium hydroxide under high temperature and stirring until the precipitation is completed. It is also possible to use alkali-free bases (such as ammonia, ammonium carbonate, ammonium hydrogencarbonate, ammonium amide, ammonium oxalate, malonic acid). Ammonium, urotropin, urea, etc. are treated. The type of salt used is generally not critical: since what is important in this procedure is primarily the solubility of the salt in water, one criterion is its good solubility in water necessary to prepare a relatively high concentration of salt solution. It is self-evident that when selecting the salt of the individual components, it is naturally only possible to select salts having their anions which do not cause disturbances (whether caused by undesired precipitation or hindered or prevented by precipitation).

The precipitate obtained during such precipitation reactions is generally chemically non-homogeneous and consists in particular of a mixture of oxides, hydrated oxides, hydroxides, carbonates and insoluble and basic salts of the metals used. Regarding the filterability of the precipitate, it may prove to be advantageous if it ages, i.e., if it is left alone for a certain period of time after precipitation, as the case may be at a high temperature and at the same time passing air.

The precipitate obtained after the precipitation process can be further processed by a method known per se to obtain a catalyst for the variations (i) and (ii) of the process of the present invention. The precipitate was washed first. The alkali metal content introduced by the (mineral) base which may be used as a precipitating agent may be affected by the duration of the washing and the temperature and amount of the washing water. In general, prolonged washing or increasing the temperature of the wash water will reduce the alkali metal content. After washing, the precipitate is usually dried at 80 to 200 ° C, preferably 100 to 150 ° C, and then calcined. The calcination can be carried out at a temperature between 300 and 800 ° C, preferably at 400 to 600 ° C, in particular at 420 to 550 ° C.

In another embodiment, the catalysts of variants (i) and (ii) used in the process of the invention may be impregnated with a transition metal salt solution, for example, as a powder or a shaped article (such as strands, ingots, beads). Alumina (Al ₂ O ₃ ), titanium dioxide (TiO ₂ ), cerium oxide (SiO ₂ ), zirconium dioxide (ZrO ₂ ) are present in the form of a granule or a ring or a mixture of at least two of the above oxides.

The alumina used is, for example, in the form of amorphous, gamma, θ and/or δ, in the form of aluminum oxyhydroxide (boehmite), preferably in the form of gamma.

The zirconium dioxide used may be, for example, in the form of an amorphous, monoclinic, tetragonal or cubic variant, preferably monoclinic, tetragonal and cubic variants. Especially preferred is a single oblique variant.

The shaped article can be produced by a method known per se.

In one embodiment of the invention, from 0.1 to 120% by weight of the catalyst based on the alpha-hydroxycarboxylic acid is used.

In one embodiment of the process of the invention, it is carried out at a temperature in the range of from 150 to 280 ° C, preferably from 170 to 250 ° C.

In one embodiment of the process of the invention, it is carried out at a pressure in the range from 10 to 300 bar, preferably from 100 to 250 bar, particularly preferably from 150 to 200 bar.

The process of the invention can be carried out batchwise, continuously or semi-continuously.

In one embodiment of the invention, the entire reaction mixture or certain components of the reaction mixture (e.g., a nitrogen-containing compound (c) (specifically, ammonia) or a solution of an alpha-hydroxycarboxylic acid) may be recycled.

In one embodiment of the invention, the process of the invention may be carried out at a substantially constant temperature (e.g., at a temperature of 10 ° C or less, preferably 5 ° C or less than 5 ° C during the process of the invention) ) in batches.

In one embodiment of the invention, the duration of execution of the method of the invention The range is from 1 minute to 48 hours. If it is desired to continuously perform the method of the invention, the duration is understood to mean the mean residence time.

In one embodiment of the invention, the process of the invention is in the form of a suspension of at least one catalyst of variant (i) or (iii) and, in particular, in the range of from 1 to 48 hours, preferably from 2 to 24 hours. The reaction time is carried out.

In another embodiment of the invention, the process of the invention is carried out using a catalyst of variant (ii) and, in particular, a reaction time in the range of from 1 minute to 10 hours, preferably from 30 minutes to 5 hours.

The time period for activities such as heating, cooling, treating the reaction mixture, separating the racemic α-amino acid, decompressing or activating the catalyst should not be taken into account when calculating the time.

In one embodiment of the invention, mixing can be used to carry out the method of the invention, for example by stirring, shaking, rolling, circulating, twitching via a static mixer or a pneumatic mixer.

Without intending to be bound by a particular theory, it is assumed that during the process of the invention the alpha-hydroxycarboxylic acid is first oxidized (i.e., dehydrogenated) to an alpha-ketocarboxylic acid, followed by conversion of the alpha-ketocarboxylic acid to the corresponding The α-imidocarboxylic acid is then reduced to the racemic α-aminocarboxylic acid.

This results in a reaction mixture comprising water and a salt of a racemic alpha-amino acid or a racemic a-amino acid, and may have other components such as a catalyst (residue), such as an alpha-hydroxycarboxylic acid or Starting material of the nitrogen compound (c) (specifically ammonia) or further decomposition products of the α-hydroxycarboxylic acid, such as propionic acid, acetic acid or formic acid.

In one embodiment of the invention, the resulting reaction mixture is treated. in In a particular embodiment of the invention, the racemic alpha-amino acid or racemic alpha-amino acid salt is isolated.

With regard to processing, for example, one or more of the following activities can be performed: (i) deactivation of the catalyst, (ii) separation of the activatable or deactivated catalyst, for example by filtration (eg filter cake filtration or cross flow) (iv) by means of sedimentation or centrifugation, (iii) complete or partial removal of water and nitrogen compounds (c) (specifically ammonia), for example by evaporation, distillation or spray drying, (iv) with acid, specific words Neutralizing the nitrogen compound (c) or, in particular, ammonia with Brönsted acid (for example with sulfuric acid or hydrochloric acid), (v) separating by-products, for example by using the alpha-hydroxycarboxylic acid Formed by reduction, (vi) adjusting the pH, for example, using Bronsted acid or Brönsted base to adjust the pH, (vii) separating from unreacted α-hydroxycarboxylic acid by means of an ion exchanger Alpha-amino acid.

In one embodiment of the invention, the racemic alpha-amino acid or racemic alpha-amino acid salt is recrystallized for purification purposes. Various solvents can be used for recrystallization. Suitable are, for example, water and aqueous mixtures, such as mixtures of water and ethanol. Preferably, it is recrystallized from water or an aqueous alkali solution having a pH in the range of 7.1 to 14, preferably 9 to 12. A suitable aqueous base solution is a dilute solution of potassium hydroxide and especially a dilute solution of sodium hydroxide.

Recrystallization can be carried out one or more times. Crystalline racemic alpha-amino acids or salts of racemic alpha-amino acids which have been crystallized, for example by decantation or filtration or filtration The combination with decantation is separated from the mother liquor.

In one embodiment, a pure racemic alpha-amino acid or a pure racemic alpha-amino acid salt (eg, a pure sodium salt or a pure potassium salt) or a partially neutralized pure racemic alpha-amine is obtained. Base acid.

Another embodiment of the present invention provides a mixture comprising (a) racemic α-amino acid in the range of 91 to 99.9% by weight, preferably 95 to 99.9% by weight, and (b) 0.1 to 9% by weight. Preferably, the corresponding α-hydroxycarboxylic acid in the range of 0.5 to 5% by weight is selected from the group consisting of glycolic acid, lactic acid, malic acid, 2-hydroxyglutaric acid, isocitric acid, hydroxymalonic acid and tartaric acid, in each case It is in pure form, or preferably partially or completely neutralized by potassium or ammonium or especially by sodium, wherein the % by weight data is in each case based on the total mixture and is likewise provided by the invention.

The racemic α-amino acid is selected from the group consisting of glycine and, in each case, alanine, aspartic acid, glutamic acid, 1-aminopropane-1,2,3-tricarboxylic acid, 2-amino group Malonic acid, 2-amino-3-hydroxysuccinic acid and 2,3-diaminosuccinic acid racemate.

The corresponding alpha-hydroxycarboxylic acid (b) may be enantiomerically enriched or preferably racemic.

The proof that the racemic α-amino acid (a) is a racemate is provided, for example, by an optical rotation assay.

In a preferred embodiment of the invention, in the mixture of the invention, the racemic α-amino acid (a) is selected from the group consisting of racemic α-alanine and α-hydroxycarboxylic acid (b). It is preferably selected from the group consisting of racemic lactic acid, in each case in pure form, or preferably partially or completely neutralized with potassium or ammonium or especially sodium.

Mixtures of the invention can be prepared, for example, by the process of the invention.

The invention further provides for the use of a mixture of the invention for the preparation of a tweaking agent. The invention further provides a process for preparing a tweaking agent using at least one of the mixtures of the invention.

The mixture of the invention can be used, for example, to prepare a miscible agent. For example, using racemic α- alanine, lactic acid and the racemic mixture, for example by ethoxylation and for the subsequent oxidation of the alcohol group CH ₂ -OH, or HCN / HCHO by Lancaster Rake synthesis to prepare racemic methyl glycine diacetic acid (MGDA). In this case, it is not difficult to obtain a part of lactic acid (specifically, racemic lactic acid) during the preparation of MGDA. A mixture of lactic acid and racemic MGDA in pure acid form or, for example, completely or partially neutralized with sodium or potassium is obtained.

The invention further provides formulations comprising at least one mixture of the invention.

In particular, the present invention provides a mixture comprising (a) lactic acid in a preferred racemic form in the range of from 0.1 to 5% by weight, (b) racemic N in the range of from 95 to 99.9% by weight, N-methylglycine diacetic acid, in each case in pure form, or preferably partially or completely neutralized with potassium or ammonium or especially sodium.

The invention is illustrated by working examples.

Data (%) is a percentage by weight unless otherwise explicitly stated.

In the context of embodiments, the term "catalyst" also refers to a deactivated catalyst.

I. Preparation of catalyst Preparation of I.1 Catalyst I.1

Under stirring, the following materials were simultaneously introduced into a stirred vessel heated to 65 ° C: - an aqueous solution of nickel nitrate, cobalt nitrate, copper nitrate, aluminum nitrate and tin (II) chloride, which contained 3.9% converted, 3.9% Co, 1.9% Cu, 5.5% Al ₂ O ₃ and 0.5% Sn ("transition metal salt solution") and - 20% by weight aqueous sodium carbonate solution.

The transition metal salt solution is fed into the vessel at a constant flow. The metering of the aqueous solution of sodium carbonate at a concentration of 20% by weight was adjusted so that the pH of 5.7 was kept constant (measured using a glass electrode). A suspension is formed by precipitating nickel, cobalt, aluminum, copper, and a tin compound. The temperature of the suspension was 65 °C. When the precipitation was completed, air was blown for one hour, and then the pH of the suspension was adjusted to 7.4 using a sodium carbonate solution. The suspension obtained in this way was filtered and the filter cake was washed with demineralized water until the conductivity of the filtrate was about 20 mS. The filter cake was then dried in a dry box at a temperature of 150 °C. The basic carbonate mixture obtained in this way was then calcined at a temperature of 500 ° C for 4 hours. The catalyst block was then mixed with 3% by weight of graphite and shaped to give a 3.3 mm ingot. The ingot obtained in this manner is reduced in hydrogen at a temperature of 280 to 300 ° C for at least 12 hours. The reduced catalyst was passivated at room temperature in "lean" air (O ₂ content of up to 5% by volume, air in N ₂ ). The composition of catalyst I.1 obtained in this way is shown in Table I.

Preparation of I.2 Catalyst I.2

Under stirring, the following materials were simultaneously introduced into a stirred vessel heated to 65 ° C: - an aqueous solution of nickel nitrate, cobalt nitrate, copper nitrate and zirconium acetate containing 7% by weight of NiO, 7% by weight of CoO 3.25% by weight of CuO and 7.75% by weight of ZrO ₂ ("transition metal salt solution") and - 20% by weight of aqueous sodium carbonate solution.

The transition metal salt solution is fed into the vessel at a constant flow. The metering of a 20% strength by weight aqueous sodium carbonate solution was adjusted so that the pH of 7.5 was kept constant (measured using a glass electrode). A suspension is formed by precipitating nickel, cobalt, copper and zirconium compounds. The temperature of the suspension was 65 °C. When the precipitation was completed, the suspension obtained in this way was filtered, and the filter cake was washed with demineralized water until the conductivity of the filtrate was about 20 mS. The filter cake was then dried in a dry box at a temperature of 120 °C. The basic carbonate mixture obtained in this way was then calcined at a temperature of 400 ° C for 2 hours. The catalyst block was then shaped to give a 3.3 mm ingot. The ingot obtained in this manner is reduced in hydrogen at a temperature of 280 to 300 ° C for at least 12 hours. The reduced catalyst was passivated at room temperature in "lean" air (O ₂ content of up to 5% by volume, air in N ₂ ). The composition of catalyst I.2 obtained in this way is shown in Table I.

^* ): catalyst composition (% by weight); the remainder to 100% by weight is the support.

II. Preparation of α-alanine (racemic) II.1 Preparation of α-alanine with Raney Nickel Catalyst

An aqueous solution of 10 g of nickel hydride as a catalyst, 74 g of a 36% by weight sodium salt of L-lactic acid and 45 g of liquid ammonia were introduced as an initial charge into a 300 ml autoclave. 20 bar of hydrogen was injected and the mixture was heated to 200 °C. The pressure was then increased to 200 bar by further injection of hydrogen. Next, the mixture was stirred at 200 bar of hydrogen and 200 ° C for 24 hours. After 16 hours, an aliquot was taken and the conversion was determined to be 64% (based on lactic acid and determined by ¹ H NMR spectroscopy). After a total of 24 hours, the mixture was cooled to room temperature and depressurized, and the catalyst was filtered off and 45 g of water and unreacted ammonia were distilled off.

This gave a mixture comprising 79 mol% of racemic alpha-alanine and 21 mol% of racemic lactic acid (in each case in the form of the sodium salt). The residual moisture is 20% by weight based on the sum of racemic α-alanine and racemic lactic acid (in each case in the form of a sodium salt).

II.2 Preparation of α-alanine with Raney Nickel Catalyst

An aqueous solution of 10 g of nickel hydride as a catalyst, 74 g of a 36% by weight sodium salt of L-lactic acid, and 45 g of liquid ammonia were introduced as an initial charge into a 300 ml autoclave. 20 bar of hydrogen was injected and the mixture was heated to 210 °C. Next, the pressure was increased to 200 bar by further injection of hydrogen. Next, the mixture was stirred at 200 bar of hydrogen and 210 ° C for 24 hours. After 16 hours, an aliquot was taken and the conversion was determined to be 89% (based on lactic acid and determined by ¹ H NMR spectroscopy). After a total of 24 hours, the mixture was cooled to room temperature and depressurized, and the catalyst was filtered off and 45 g of water and unreacted ammonia were distilled off.

This gave a mixture GM-AM.1 of the invention comprising 92 mol% of racemic alpha-alanine and 8 mol% of racemic lactic acid (in each case in the form of the sodium salt). It corresponds to a weight ratio of 91.9% by weight of racemic alpha-alanine to 8.1% by weight of racemic lactic acid (in each case in terms of free acid).

GM-AM.1 is extremely easy to handle and produces a mixture of (±)-MGDA and racemic lactic acid.

II.3 Preparation of α-alanine by means of Ni-Co-Cu-Sn catalyst

10 g of catalyst I.1 was fed into a catalyst basket made of stainless steel. The catalyst basket filled in this manner was placed in a 300 ml autoclave and treated with hydrogen at 250 ° C for a period of 24 hours. Thereby the catalyst is activated. The system was depressurized and cooled to room temperature, and 74 g of a 36% strength by weight aqueous solution of L-lactic acid sodium salt and 45 g of liquid ammonia were added. 20 bar of hydrogen was injected and the mixture was heated to 200 °C. The pressure was then increased to 200 bar by further injection of hydrogen. Next, the mixture was stirred at 200 bar of hydrogen and 200 ° C for 24 hours. After 16 hours, an aliquot was removed and the conversion was determined to be 64% (based on lactic acid and determined by ¹ H NMR spectroscopy). After a total of 24 hours, the system was cooled to room temperature and depressurized, and the catalyst basket was removed with the catalyst, and 45 g of water and unreacted ammonia were distilled off.

This gave a mixture comprising 79 mol% of racemic alpha-alanine and 21 mol% of racemic lactic acid (in each case in the form of the sodium salt). The residual moisture was 15% by weight based on the sum of racemic α-alanine and racemic lactic acid (in each case in the form of a sodium salt).

Analysis of the gas space above the reaction mixture shows the volume fraction of methane It is 0.15%.

II.4 Preparation of α-alanine by means of Ni-Co-Cu-Sn catalyst

10 g of catalyst I.1 was fed into a catalyst basket made of stainless steel. The catalyst basket filled in this manner was placed in a 300 ml autoclave and treated with hydrogen at 250 ° C for a period of 24 hours. Thereby the catalyst is activated. The system was depressurized and cooled to room temperature, and 74 g of a 36% strength by weight aqueous solution of L-lactic acid sodium salt and 45 g of liquid ammonia were added. 20 bar of hydrogen was injected and the mixture was heated to 210 °C. The pressure was then increased to 200 bar by further injection of hydrogen. The mixture was stirred at 200 bar of hydrogen and 210 ° C for 24 hours. After 16 hours, an aliquot was taken and the conversion was determined to be 85% (based on lactic acid and determined by ¹ H NMR spectroscopy). After a total of 24 hours, the mixture was cooled to room temperature and depressurized, and the catalyst basket was removed together with the catalyst, and 45 g of water and unreacted ammonia were distilled off.

This gave a mixture of the invention comprising 92 mol% of racemic alpha-alanine and 8 mol% of racemic lactic acid (in each case in the form of the sodium salt). Its composition corresponds to the mixture GM-AM.1 of the present invention of Example 2.

II.5 Continuous preparation of α-alanine by means of Ni-Co-Cu catalyst

500 ml of catalyst I.2 was fed into a fixed bed reactor (dimension: length 2 m, circle diameter: 3 cm) using a reflux pump. The catalyst was treated with hydrogen at 280 ° C for 24 hours without pressure. Thereby the catalyst is activated. Next, the fixed bed reactor was operated so that the fixed bed was continuously fed from the bottom to the top at 55 g/h of a 55 wt% aqueous solution of L-lactic acid sodium salt, 227 g/h of gaseous ammonia, and 100 l/h (stp) of hydrogen continuously. operating. The reflux pump requires 502 g/h of the reaction mixture. A temperature of 210 ° C and a pressure of 200 bar were established. After decompression, An aqueous solution containing racemic α-alanine and sodium salt of racemic lactic acid having a molar ratio of 83:17 was obtained.

II.6 Continuous preparation of α-alanine by means of Ni-Co-Cu catalyst

500 ml of catalyst I.2 was fed into a fixed bed reactor (dimension: length 2 m, round diameter: 3 cm). The catalyst was treated with hydrogen at 280 ° C for 24 hours without pressure. Thereby the catalyst is activated. Next, the fixed bed reactor was operated so that the fixed bed was continuously fed from bottom to top at 69 g/h of 60 wt% aqueous solution of L-lactic acid sodium salt, 77 g/h of gaseous ammonia and 50 l/h (stp) of hydrogen continuously. operating. Establish a temperature of 200 ° C and a pressure of 50 bar. The system was depressurized via a control valve to give the mixture GM-AM.6 of the invention comprising a race ratio of 92:8 racemic alpha-alanine and racemic lactic acid (in each case in the form of a sodium salt) ).

GM-AM.6 is extremely easy to handle and produces a mixture of (±)-MGDA and racemic lactic acid.

Claims (15)

A process for the preparation of racemic α-amino acid or glycine, wherein the corresponding α is selected from the group consisting of glycolic acid, lactic acid, malic acid, α-hydroxyglutaric acid, isocitric acid, hydroxymalonic acid and tartaric acid - at least one salt of a hydroxycarboxylic acid or the corresponding alpha-hydroxycarboxylic acid is reacted with at least one nitrogen compound (c) in the presence of hydrogen in the presence of at least one heterogeneous catalyst comprising at least one transition metal, wherein the nitrogen compound ) is selected from the group consisting of primary amines and secondary amines and ammonia. The method of claim 1, wherein the heterogeneous catalyst is selected from the group consisting of Raney metal and a transition metal applied to the solid support. The method of claim 1 or 2, wherein the transition metal is selected from the group consisting of Ni, Cu, and Co. The method of claim 1 or 2, wherein during the method, the transition metal in the heterogeneous catalyst is present in the zero oxidation state for at least a portion of the time. The method of claim 1 or 2, wherein the nitrogen compound (c) is selected from the group consisting of ammonia. The method of claim 1 or 2, which is carried out at a temperature in the range of from 150 to 280 °C. The method of claim 1 or 2, wherein the α-hydroxycarboxylic acid is selected from the group consisting of racemic lactic acid, (-)-lactic acid, and (+)-lactic acid. The method of claim 1 or 2, wherein the salt of the α-hydroxycarboxylic acid is selected from the group consisting of alkali metal salts and ammonium salts of α-hydroxycarboxylic acids. The method of claim 1 or 2 is carried out at a pressure in the range of 10 to 300 bar. The method of claim 1 or 2, which is carried out in an aqueous medium. The method of claim 1 or 2, which comprises recrystallization for purifying the prepared racemic α-amino acid or glycine. a mixture comprising (a) racemic alpha-amino acid in the range from 91 to 99.9% by weight, (b) corresponding alpha-hydroxycarboxylic acid in the range from 0.1 to 9 weight percent, in each case Pure form or partial or complete neutralization, wherein the data in % by weight is in each case based on the total mixture. A mixture according to claim 12, wherein the racemic α-amino acid (a) is selected from the group consisting of racemic α-alanine and the racemic α-hydroxycarboxylic acid (b) is selected from the group consisting of racemic lactic acid. A formulation comprising at least one mixture as claimed in claim 12 or 13. A use of a mixture of claim 12 or 13 for the preparation of a tweaking agent.