FR2890964A1 - AMMONIACAL HYDROLYSIS OF A-AMINO ACID CYANHYDRIN CONTINUOUSLY AND WITHOUT ISOLATING INTERMEDIATE PRODUCTS - Google Patents

Abstract

The present invention relates to a process for the preparation of a continuous α-amino acid (or alpha-amino acid), an alpha-amino acid of general formula (I) by ammoniacal hydrolysis and from alpha-acid cyanohydrin. amine compound of the general formula (II) wherein R and R ', which may be identical or different, form a ring, each represent: -H; - an alkyl, haloalkyl or heteroaryl group containing between 1 and 30 carbon atoms, in a chain linear or branched; - an alkenyl or alkynyl group containing from 2 to 30 carbon atoms, in a straight or branched chain; - one or more cycloalkyl, cycloacenyl or cycloalkynyl groups containing from 3 to 30 carbon atoms, in a straight or branched chain; one or more aryl or heteroaryl groups containing between 3 and 10 carbon atoms per ring and optionally substituted by R; an alkaryl or aralkyl group containing between 1 and 30 carbon atoms; aryl and alkyl radicals having the above definitions; - an alkoxyalkyl, alkylthioalkyl, alkylsulphonylalkyl, alkylaminoalkyl group containing from 1 to 30 carbon atoms, in a straight or branched chain; - one or more heterocyclic groups containing between 5 and 10 carbon atoms by ring, or a combination of one or more groups above, said groups being optionally substituted with R, with one or more nitro, cyano, hydroxy, carboxy, carbonyl or amino groups, with one or more halogens or with one or more functions nitrile, cyanohydrin, aldehyde, and, in the case where R and R 'together form a ring, this ring is as defined above.

Description

R R'-TCOOH (I) H2N

R

R '- T-CN

HO

  The field of the present invention is that of the preparation of an α-amino acid (or α-amino acid), from the corresponding α-amino acid cyanohydrin, by ammoniacal hydrolysis.

  The ammoniacal hydrolysis reaction concerned by the present invention is the following: ## STR2 ## R and R 'having the meanings defined hereinafter.

  Processes for preparing α-amino acids generally involve various reaction steps. For example, the process for the preparation of methionine has for many years been followed by 2-hydroxy-4 (methylthio) butyronitrile (or HMTBN) followed by hydantoin of methionine, both of which must be isolated.

  An object of the present invention is to provide a process for preparing an α-amino acid from the corresponding α-amino acid cyanohydrin, without isolating intermediates such as, for example, previously defined.

  In addition, the α-amino acid preparation involves, for example, very often a hydrolysis with NaOH, which has the disadvantage of generating sodium salt (Na 2 SO 4 and / or NaCl) in a significant amount. This is particularly the case during the saponification of hydantoin methionine, which leads to methionine.

  Another object of the present invention is to obtain aaminated acid from its corresponding cyanohydrin, without co-production of salt.

  The present invention makes it possible to pass directly from the cyanohydrin of an α-amino acid given to said α-amino acid by ammoniacal hydrolysis, without isolating or separating intermediates, which has never been described to date. The invention has an industrial value

R

CN HO

  considerable. Indeed, it provides many technical advantages, and in particular it considerably reduces the industrial equipment to be implemented and the interventions to be performed during the process for preparing α-amino acids.

  The present invention provides a process for the continuous preparation of an α-amino acid of general formula (I)

R H2N

  COOH (I) wherein R and R ', identical or different, optionally form a ring, each represent: -H; an alkyl, haloalkyl or heteroaryl group containing between 1 and 30 carbon atoms, in a linear or branched chain; an alkenyl or alkynyl group containing between 2 to 30 carbon atoms, in a linear or branched chain; one or more cycloalkyl, cycloacenyl or cycloalkynyl groups containing between 3 and 30 carbon atoms, in a linear or branched chain; one or more aryl or heteroaryl groups containing between 3 and 10 carbon atoms per ring and optionally substituted with R; an alkaryl or aralkyl group containing between 1 and 30 carbon atoms, the terms aryl and alkyl having the above definitions; an alkoxyalkyl, alkylthioalkyl, alkylsulphonylalkyl or alkylaminoalkyl group containing between 1 and 30 carbon atoms, in a linear or branched chain; one or more heterocyclic groups containing between 5 and 10 carbon atoms per cycle; or a combination of one or more groups above, said groups being optionally substituted with R, with one or more nitro, cyano, hydroxy, carboxy, carbonyl or amino groups, with one or more halogens or with one or more nitrile functions, cyanohydrin, aldehyde, and, in the case where R and R 'together form a ring, this ring is as defined above, from the corresponding cyanohydrin of general formula (II)

R

R'-TCN (II)

HO

  in which R and R 'are as defined above, the method according to which ammoniacal hydrolysis (1) of (II) is carried out, characterized in that (a) hydrolysis is carried out (1), in phase aqueous, continuously and without isolating intermediates, at a temperature not exceeding 250 C, starting from a molar ratio NH3 / (II) between 5 and 50, and a molar proportion CO2 / (II) between 1 and 10, to obtain an exit mixture (5) mainly comprising the amino acid (I), carbon dioxide and dissolved ammonia, and products derived from (II); (b) products derived from (II), carbon dioxide and ammonia are recycled to hydrolysis (a).

  By "continuous" it is meant that the process is carried out with a continuous supply of starting materials. This further implies a continuous withdrawal of the products formed.

  According to the invention, the term "alkyl" denotes a linear or branched hydrocarbon radical of 1 to 30 carbon atoms, such as, by way of indication, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, isobutyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl or icosyl. The alkyl group defined above may comprise one or more halogen atoms (fluorine, chlorine, bromine or iodine). In this case, we speak of "haloalkyl" group. The alkyl group may further comprise heteroatoms selected from P, O, N, S and Se. In this case, we speak of "heteroalkyl" group.

  By "alkenyl" is meant a linear or branched hydrocarbon chain of 2 to 30 carbon atoms comprising one or more double bonds. Examples of alkenyl groups are alkenyl groups carrying a single double bond such as -CH-CH = CH-CH 2, vinyl or allyl.

  By "alkynyl" is meant a linear or branched hydrocarbon chain of 2 to 30 carbon atoms comprising one or more triple bonds. Examples of alkynyl groups are alkynyl groups carrying a single triple bond such as CH2-CE CH.

  The term "cycloalkyl" refers to saturated hydrocarbon groups which may be mono- or polycyclic and comprise from 3 to 10 carbon atoms. These are, for example, monocyclic cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl and cyclododecyl.

  By "cycloalkenyl" is meant according to the invention a group derived from a cycloalkyl group as defined above, having one or more double bonds, for example two double bonds.

  "Cycloalkynyl" means according to the invention a group derived from a cycloalkyl group as defined above, having one or more triple bonds, for example a triple bond.

  The term "aryl" represents a mono- or polycyclic aromatic hydrocarbon group having 3 to 10 carbon atoms per ring, such as phenyl or naphthyl.

  The term "heteroaryl" refers to monocyclic or polycyclic aromatic groups comprising from 3 to 10 carbon atoms per ring and comprising 1, 2 or 3 endocyclic heteroatoms per ring selected from P, O, N, S and Se. Examples are furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, oxadiazolyl, triazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrazinyl and triazinyl groups.

  By "alkaryl" is meant an alkyl group as defined above, substituted with an aryl group.

  By "aralkyl" is meant an alkyl group as defined above, substituted with an aryl group.

  By "alkoxyalkyl" is meant an O-alkyl group having 1 to 30 carbon atoms, especially methoxy, ethoxy, propoxy and butoxy. "Alkylthioalkyl", "alkylsulfonylalkyl" and "alkylaminoalkyl" groups furthermore contain one or more sulfur atoms, one or more sulfonyl groups and one or more amine functions, respectively.

  The term "heterocyclic group" refers to saturated or unsaturated, monocyclic or polycyclic carbon rings having 1, 2 or 3 endocyclic heteroatoms selected from P, O, N, S and Se. These are generally derivatives of the heteroaryl groups described above. Examples of unsaturated heterocycles are dihydrofuryl, dihydrothienyl, dihydropyrrolyl, pyrrolinyl, oxazolinyl, thiazolinyl, imidazolinyl, pyrazolinyl, isoxazolinyl, isothiazolinyl, oxadiazolinyl, pyranyl and the monounsaturated derivatives of piperidine, dioxane, piperazine, trithiane, morpholine of dithiane, thiomorpholine, as well as tetrahydropyridazinyl, tetrahydropyrimidinyl, and tetrahydrotriazinyl.

  The groups defined above can, according to the invention, be substituted with R, with one or more nitro, cyano, hydroxy, carboxy, carbonyl or amino groups, with one or more halogens, or with one or more nitrile, cyanohydrin or aldehyde functions. By "without isolating intermediates" is meant that at no time during the hydrolysis step is an intermediate product isolated or separated, in particular for evacuating it. In other words, the hydrolysis reaction is carried out in "one-pot". According to the present invention, the ammoniacal hydrolysis is carried out continuously, without intermediate separation or fractionation, and in a manner known per se, for example with a tubular reactor, or in a stepped manner with a cascade of agitated reactors arranged in series. .

  The realization of the method according to the invention in "one-pot" offers a particular advantage when the process is conducted at the industrial level.

  By "product derived from (II)" is meant any compound that derives directly or indirectly from the compound (I). This compound is also likely to lead directly or indirectly to the amino acid (I).

  By way of example, in the case of the preparation of methionine, these are products derived from 2-hydroxy-4- (methylthio) butyronitrile, methionine cyanohydrin. In this case, it may especially be 2-amino-4- (methylthio) butanenitrite (AMTBN), AMTBN bicarbonate, hydantoin of methionine, ureidobutyramide, hydantoïque acid or 2-amino- 4- (methylthio) butanamide (AMTBM). These compounds may or may not be "methioninogenic", that is to say they may lead, directly or indirectly, to methionine by ammoniacal hydrolysis.

  Figure 1 shows, generically, a plant for producing α-amino acid from the corresponding amino acid cyanohydrin by ammonia hydrolysis.

  Fig. 2 shows an α-amino acid production plant according to one embodiment of the present invention.

  FIG. 3 is a graphical representation of the reaction kinetics of the hydrolysis of 2-hydroxy-4- (methylthio) butyronitrile to methionine by ammoniacal hydrolysis.

  Figure 4, in turn, shows graphically the kinetics of phenylglycine production from mandelonitrile by ammoniacal hydrolysis.

  As an indication, examples of α-amino acids obtainable according to the present invention are the following: methionine, phenylglycine, glycine, norleucine, α-methylleucine, (3, (3-diphenylalanine, 3-methylphenylalanine, lysine.

  According to one embodiment of the present invention, ammonia hydrolysis is carried out without a catalyst, for example without a solid catalyst, in particular of the metal oxide type.

  By "catalyst" is meant any compound not consumed in the hydrolysis reaction and found completely when the reaction is complete. In general, there is no stoichiometric ratio between the catalyst and the reagents. According to one embodiment of the present invention, the process proceeds in the absence of catalyst, which has considerable advantages, industrially speaking.

  The process for preparing the α-amino acid from the corresponding cyanohydrin involves various reaction steps, which according to the present invention proceed concomitantly. These different reaction stages consume and produce NH3 and CO2. By proceeding continuously, an equilibrium is created between the moles of NH3 and CO2 produced and those consumed, so that these compounds, although not appearing in the overall assessment of the reaction, can not be considered catalysts. .

  According to an embodiment of the present invention, before the recycling step, the outlet mixture is expanded, then the expanded outlet mixture is separated into a liquid stream enriched in α-amino acid, and a gaseous stream enriched with ammonia. and carbon dioxide.

  In addition, according to one embodiment of the present invention, the liquid stream enriched in α-amino acid, in solid α-amino acid, evacuated, and mother liquor depleted in α-amino acid and containing the products derived from α-amino acid are separated. the α-amino acid cyanohydrin, said mother liquors being recycled, after raising their pressure towards hydrolysis.

  The basic method according to the present invention is now described with reference to FIG.

  The process implements hydrolysis 1 continuously, in the aqueous phase. This hydrolysis takes place without isolation or separation of intermediates, as defined above. The hydrolysis 1 is fed with an aqueous solution 2, industrial, comprising α-amino acid cyanohydrin (compound of general formula II) corresponding to the α-amino acid (compound of general formula I) that is desired to prepare. The supply of the reactor 1 in aqueous solution 2, the pressure of which has previously been raised by a pump 4, is carried out via a feed pipe.

  Before introduction into the reactor 1, to the aqueous solution 2 comprising the compound of the general formula II is added an aqueous phase containing ammonia and CO2, via the feed pipe 3, which is mixed in the aqueous solution 2 comprising the compound II.

  The aqueous cyanohydrin solution has a cyanohydrin concentration of the α-amino acid which is preferably greater than 40%. For example, an industrial cyanohydrin solution of 65% or more can be used. The solution further comprises water and related by-products, mainly from the synthesis of said cyanohydrin, for example hydrogen cyanide and sulfuric acid.

  According to the invention, the ammoniacal hydrolysis takes place from an aqueous solution of cyanohydrin, which has many industrial advantages. In particular, the use of an aqueous cyanohydrin solution avoids having to use a "stripping" column (or steam distillation column) in order to recover the solvent. In addition, this has advantages in terms of cost and handling.

  According to the present invention, while the temperature is set, the pressure is imposed to have a homogeneous phase. The temperature is raised in the reactor 1, at a temperature ranging from the inlet to the outlet of the latter, between the temperature of the mixture (ie between 20 ° C. and 90 ° C.) and 250 ° C. According to a preferred mode of the invention, the hydrolysis 1, according to step (a), is carried out at a temperature ranging between 20 and 200 C. For operation in aqueous homogeneous phase, the pressure must be between 5 and 100 bar ( preferably about 20 bar).

  In the reaction, the temperature in the reactor increases the temperature of the mixture (i.e., between 20 ° C. and 90 ° C.) to a relatively high temperature.

  The molar proportions (11) / NH3 are between 1/5 and 1/50, for example of the order of 1/20 at the inlet of the reactor 1, and consequently there is a very large molar excess of ammonia compared compound of general formula II. The molar proportions (11) / CO2 are between 1 and 1/10, for example of the order of 1/3 at the inlet of the reactor 1.

  According to one embodiment of the present invention, the hydrolysis (a) is carried out in the presence of hydrocyanic acid, present in a molar proportion HCN / (II) not exceeding 0.1.

  According to one embodiment of the present invention, HCN can be in the form of cyanide ions.

  An exit mixture comprising principally the compound of the general formula I, CO 2 and dissolved NH 3 is obtained at the reactor outlet 1 by hydrolysis of the compound of the general formula II.

  This mixture is expanded, for example at atmospheric pressure, by an expansion valve 6, in line 5, before being introduced into a "stripping" column 10 (also called a steam distillation column).

  In column 10, the expanded mixture introduced is separated into a liquid stream 12 enriched in α-amino acid and a gaseous stream 11 enriched with NH 3 and O 2.

  At the column head 10, the gas stream enriched in NH 3 and CO 2 and which also comprises water, is condensed. The stream 22 is then stored at 20. The storage 20 optionally comprises a gas purge 21.

  The aqueous phase 3 containing ammonia and CO2 is recycled to the hydrolysis reactor 1, via a feed pipe 3, and after raising its pressure 7.

  It is also possible according to the present invention to provide a supply line 8 which supplies the pipe 3 with ammonia, CO2 and / or water, before raising the pressure. Such conduct allows the adjustment of the title to ammonia, 002 and / or water if necessary.

  According to the present invention, "ammonia" means a gaseous phase containing substantially NH3; while "ammonia" means a liquid phase containing substantially NH4OH.

  Similarly, when a "gas phase containing CO2" is used, it is meant a phase containing substantially CO2 in gaseous form; while, when mention is made of "aqueous phase containing 002", it is meant a phase containing substantially H2CO3.

  The term "substantially" means that the phase in question comprises an excess of the compound in question greater than 50%, more particularly greater than 70%.

  A liquid stream enriched in α-amino acid, ie an aqueous solution of α-amino acid, "acidified", is withdrawn at the bottom of the "stripping" column 10 via the withdrawal line 12. that is to say whose pH has been lowered.

  According to FIG. 1, this stream is cooled in a heat exchanger 30, which makes it possible to precipitate the α-amino acid. But any other means known to those skilled in the art, for example evaporation, is applicable in this case.

  The liquor thus obtained is then sent to a separator 40 which makes it possible to separate the α-amino acid in solid form, products derived from the unreacted α-amino acid cyanohydrin, remaining in the aqueous phase, called mother waters.

  At 41, the α-amino acid is recovered in solid form, while the said by-products are sent back to the reactor 1, via the supply line 48, after having raised their pressure by the pump 49. This recycling loop is particularly advantageous as it appears in the present invention.

  The basic method according to the present invention defined by reference to FIG. 1 is now specified with reference to FIG.

  According to one embodiment of the present invention, the liquid stream 12 enriched in α-amino acid is separated by staged crystallization 45 to obtain, on the one hand, α-amino acid in solid form, filtered and then dried. 47, and secondly, mother liquors 48.

  Staged crystallization 45 further generates a gas stream 41, 35 containing water and light products, referred to as "condensates". After condensation 42, stream 43 is stored at 44.

  According to one embodiment of the present invention, the hydrolysis 1 according to step (a) is carried out in a tubular reactor or in a plurality of stirred reactors (1a, 1b, 1c, 1d) arranged in series, as shown in Figure 2.

  The number of agitated reactors is indifferent. Preferably, it is greater than 3, but the maximum number is not limited.

  The following examples will make it possible to understand the advantage of the ammoniacal hydrolysis according to the present invention, and consequently the interest of a process according to the invention.

Examples

  Examples 1 to 10 illustrate the following ammoniacal hydrolysis reaction:

H H

CN

COOH

  HO H2N, that is the preparation of 2-amino-4- (methylthio) butanoic acid (hereinafter referred to as methionine), from 2-hydroxy-4 (methylthio) butyronitrile (hereinafter called HMTBN), therefore with R = CH3-S-CH2CH2 and R '= H.

  Example 11 illustrates the following ammoniacal hydrolysis reaction:

H

CN COOH

  HO H2N that is to say the preparation of glycine, from glyconitrile, and therefore with R = H and R '= H.

  Example 12 illustrates the following ammoniacal hydrolysis reaction:

H -

  ## STR2 ## that is to say the phenylglycine preparation, from mandelonitrile, and hence with R = Ph and R '= H.

Example 1 (MEA 130)

  285.25 g of ammonia solution at 30.5% by weight of NH 3 in 72.34 g of ammonium hydrogencarbonate 0 are introduced into a perfectly stirred reactor equipped with heating, temperature and pressure measurements. 78 g of sodium cyanide and, after homogenization of the medium, 42.10 g of HMTBN (concentration solution of 94.7% HMTBN in water).

  The molar ratios at the inlet of the ammoniacal hydrolysis are as follows: NH3! HMTBN: CO2 / HMTBN: 3 CN- / HMTBN: 0.05 The reaction mixture is gradually heated to 152 ° C. for 75 minutes.

  The progress of the reaction is monitored by sampling over time and analyzed by HPLC and potentiometry.

  The conversion rate of HMTBN is 100%.

  The conversion yield to methionine is 37% after 77 minutes.

  Figure 3 shows the evolution of the different products, with the following meanings: MTN = methionine HMTBN = 2-hydroxy-4 (methylthio) butyronitrile AMTBM = 2-amino-4- (methylthio) butanamide AMTBN = 2-amino-4 - (methylthio) butanenitrile

Example 2 (AME 137)

  In a perfectly stirred reactor equipped with heating, temperature and pressure measurements are introduced: 238.7 g of ammonia solution at 30.5% by weight of NH 3 102.4 g of ammonium hydrogencarbonate 1.09 g sodium cyanide and after homogenization of the medium 58.1 g of HMTBN (concentration of 97% HMTBN in water).

  The molar ratios at the inlet of the ammoniacal hydrolysis are as follows: NH3! HMTBN: 13 CO2 / HMTBN: 3 CN "/ HMTBN: 0.05 The reaction mixture is gradually heated to 152 ° C for 75 minutes.

  The progress of the reaction is monitored by sampling over time and analyzed by HPLC and potentiometry.

  The conversion rate of HMTBN is 100%.

  The conversion yield to methionine is 42% after 75 minutes.

Example 3 (AME 138)

  In a perfectly stirred reactor equipped with heating, temperature and pressure measurements, are introduced: 203.5 g of ammonia solution at 30.5% by weight of NH3 124.85 g of ammonium hydrogencarbonate 1.28 g sodium cyanide and after homogenization of the medium 70.7 g of HMTBN (concentration of 97% HMTBN in water).

  The molar ratios at the inlet of the ammoniacal hydrolysis are as follows: NH3! HMTBN: CO2 / HMTBN: 3 CN- / HMTBN: 0.05 The reaction mixture is gradually heated to 152 ° C. for 75 minutes.

  The progress of the reaction is monitored by sampling over time and analyzed by HPLC and potentiometry.

  The degree of conversion of HMTBN is 100%. The conversion yield to methionine is 37% after 75 minutes.

Example 4 (MEA 139)

  In a perfectly stirred reactor equipped with heating, temperature and pressure measurements, are introduced: 298.6 g of ammoniacal solution at 30.5% by weight of NH3 39.70 g of ammonium hydrogencarbonate 1.15 g of sodium cyanide and after homogenization of the medium 60.90 g of HMTBN (concentration of 97% HMTBN in water).

  The molar ratios at the inlet of the ammoniacal hydrolysis are as follows: NH3! HMTBN: 13 CO2 / HMTBN: 1.1 CN- / HMTBN: 0.05 The reaction mixture is gradually heated to 152 ° C. for 75 minutes.

  The progress of the reaction is monitored by sampling over time and analyzed by HPLC and potentiometry.

  The conversion rate of HMTBN is 100%.

  The conversion yield to methionine is 39% after 75 minutes.

  EXAMPLE 5 (AME 140) without addition of sodium cyanide 262.5 g of ammonia solution at 30.5% by weight of NH 3 were introduced into a perfectly stirred reactor equipped with heating, temperature and pressure measurements. , 70 g of ammonium hydrogencarbonate and after homogenization of the medium, 53.4 g of HMTBN (concentration of HMTBN at 97% in water).

  The molar ratios at the inlet of the ammoniacal hydrolysis are as follows: NH3! HMTBN: 13 CO2 / HMTBN: 1.1 The reaction mixture is gradually heated to 152 ° C. for 75 minutes.

  The progress of the reaction is monitored by sampling over time and analyzed by HPLC and potentiometry.

  The conversion rate of HMTBN is 100%.

  The conversion yield of methionine is 36% after 75 minutes.

  EXAMPLE 6 (AME 141) - Reduction of the CO2 / HMTBN Ratio In a perfectly stirred reactor equipped with heating, temperature and pressure measurements, 288.45 g of 30.5% NH 3 ammonia solution are introduced. 24.03 g of ammonium hydrogencarbonate 0.68 g of sodium cyanide and after homogenization of the medium 37 g of HMTBN (concentration of 97% HMTBN in water).

  The molar ratios at the inlet of the ammoniacal hydrolysis are as follows: NH3! HMTBN: CO2 / HMTBN: 1.1 CN- / HMTBN: 0.05 The reaction mixture is gradually heated to 152 ° C. for 75 minutes.

  The progress of the reaction is monitored by sampling over time and analyzed by HPLC and potentiometry.

  The conversion rate of HMTBN is 100%.

  The conversion yield to methionine is 41% after 75 minutes.

  EXAMPLE 7 (AME 142) - Reduction of the CO2 / HMTBN Ratio In a perfectly stirred reactor equipped with heating, temperature and pressure measurements, 236.7 d of 30.5% NH 3 ammonia solution are introduced. 61.38 g of ammonium hydrogencarbonate 0.97 g of sodium cyanide and after homogenization of the medium 51.8 g of HMTBN (concentration of 97% HMTBN in water).

  The molar ratios at the inlet of the ammoniacal hydrolysis are as follows: NH3! HMTBN: 13 CO2 / HMTBN: 2 CN- / HMTBN: 0.05 The reaction mixture is progressively up to 152 ° C. for 75 minutes.

  The progress of the reaction is monitored by sampling over time and analyzed by HPLC and potentiometry.

  The conversion rate of HMTBN is 100%.

  The conversion yield to methionine is 39% after 75 minutes.

  EXAMPLE 8 (AME 143) - Effect of Dilution In a perfectly stirred reactor equipped with heating, temperature and pressure measurements, 150.7 g of ammonia solution at 30.5% by weight of NH3 64 are introduced, 76 g of ammonium hydrogencarbonate 0.72 g of sodium cyanide g of water and after homogenization of the medium 36.6 g of HMTBN (concentration of 97% HMTBN in water).

  The molar ratios at the inlet of the ammoniacal hydrolysis are as follows: NH3! HMTBN: 13 CO2 / HMTBN: 3 CN- / HMTBN: 0.05 This example differs from Example 2 in that water is charged to the reactor.

  The reaction mixture is gradually heated to 152 ° C. for 75 minutes.

  The progress of the reaction is monitored by sampling over time and analyzed by HPLC and potentiometry.

  The conversion rate of HMTBN is 100%.

  The conversion yield of methionine is 50% after 75 minutes.

  Example 9 (AME 146) - Temperature of 185 ° C. In a perfectly stirred reactor equipped with heating, temperature and pressure measurements, 208.85 g of ammonia solution at 30.5% by weight of NH 3 89 are introduced, 7 g of ammonium hydrogencarbonate 0.96 g of sodium cyanide and after homogenization of the medium 50.8 g of HMTBN (concentration of 97% HMTBN in water).

  The molar ratios at the inlet of the ammoniacal hydrolysis are as follows: NH3! HMTBN: 13 CO2 / HMTBN: 3 CN "/ HMTBN: 0.05 The reaction mixture is gradually heated to 185 ° C. in 20 minutes.

  The progress of the reaction is monitored by sampling over time and analyzed by HPLC and potentiometry.

  The conversion rate of HMTBN is 100%.

  The conversion yield of methionine is 30% after 20 minutes.

  EXAMPLE 10 (AME 147) - Temperature of 185 ° C. In a perfectly stirred reactor equipped with heating, temperature and pressure measurements, 208.65 g of ammonia solution at 30.5% by weight of NH 3 89 are introduced. 7 g of ammonium hydrogencarbonate 0.94 g of sodium cyanide and after homogenization of the medium 51 g of HMTBN.

  The molar ratios at the inlet of the ammoniacal hydrolysis are as follows: NH3 / HMTBN: 13CO2 / HMTBN: 3 CN- / HMTBN: 0.05 The reaction mixture is gradually heated to 185 ° C. in 47 minutes. .

  The progress of the reaction is monitored by sampling over time and analyzed by HPLC and potentiometry.

  The conversion rate of HMTBN is 100%.

  The conversion yield to methionine is 39% after 47 minutes.

Example 11 (AME 118)

  In a perfectly stirred reactor in C 276 hastelloy, are charged: 365.7 g of 30% ammonia solution (365.7 g to 31.2% NH3 weight) 94.7 g of ammonium carbonate 1.1 g cyanide sodium and after homogenization of the medium, at 20 C, 40.7 g of glyconitrile (0.392 moles).

  The molar concentration is 9.64 moles / kg. The molar ratios at the inlet of the ammoniacal hydrolysis are as follows: NH 3 / glyconitrile: 20,002 / glyconitrile: 3 CN "/ glyconitrile: 0.05 The reactor is heated up to 115 C in 33 minutes and the reaction mass is cooled to room temperature.

  The HPLC analysis of the reaction mass shows: - a total conversion of the formalin cyanohydrin (glyconitrile) and - a glycine conversion rate of 57.6 mol% relative to the glyconitrile.

Example 12 (MEA 120)

  1.143 mol of ammonium hydrogen carbonate, 6.483 mol of ammonia and 0.02 mol of sodium cyanide are charged into a perfectly closed reactor stirred in the aqueous phase.

  The mixture is heated to 120 ° C. with stirring and cooled to 20 ° C.

  0.381 moles of mandelonitrile are then added via a bottle.

  The ratios relative to NH3 / CO2 / CN-, are respectively 20/3 / 0.05.

  The concentration of mandelonitrile is 7.135 moles / kg of reaction mixture.

  It is heated to 145 ° C. and the temperature of the reaction mixture is maintained at this temperature for 50 minutes.

  Samples of the medium are taken over time and analyzed by liquid phase chromatography.

  Figure 4 shows the evolution of mandelonitrile and phenylglycine during the reaction.

  The table below shows the evolution of the products (assigned an average coefficient). The degree of conversion is expressed in mol% relative to the mandelonitrile charged.

  Time in minutes 13 24 45 114 177 Phenylglycine 0.11% 0.19% 2.58% 34.78% 43.88% AMphegly 0.07% 0.71% 5.60% 22.96% 24.85% ANphegyl 61.75% 14.21% 1.01% 0.07% UREIDOphegly 1.18% 17.02% 18.06% 4.42% 1.87% AcHYDphegly 0, 30% 4.85% 6.91 % 7,79% HYDphegly 6,23% 68,39% 80,17% 22,55% 8,36% Mandelonitrile 100,00% 0,60% 0,50% 0,11% 0,33% 0,36 % Total 100.00% 70.59% 102.42% 112.76% 97.32% 95.22%

Table in which:

  Amphegly = Phenylglycine amino acid ANphegyl = Phenylglycine aminonitrile UREIDOphegly = Phenylglycine ureidobutyramide AcHYDphegly = Phenylglycine hydantoin HYDphegly = Hydantoïque acid of phenylglycine.

  After cooling to 20 C, the reaction medium is withdrawn.

  The conversion rate of mandelonitrile is greater than 99%.

  The transformation yield is 44%.

  In a glass reactor equipped with a distillation column, ammonia, carbon dioxide and part of the water are removed.

  After cooling to 20 ° C., the mixture is filtered and a precipitate is recovered which is dried to constant weight at 100 ° C.

  The cake is analyzed by HPLC and titrates more than 98% phenylglycine. Its IR spectrum is identical to the reference product.

Claims (10)

  1. Process for the continuous preparation of an α-amino acid of general formula (I) R H2N   COOH (I) wherein R and R ', identical or different, optionally form a ring, each represent: -H; an alkyl, haloalkyl or heteroaryl group containing between 1 and 30 carbon atoms, in a linear or branched chain; an alkenyl or alkynyl group containing between 2 to 30 carbon atoms, in a linear or branched chain; one or more cycloalkyl, cycloacenyl or cycloalkynyl groups containing between 3 and 30 carbon atoms, in a linear or branched chain; one or more aryl or heteroaryl groups containing between 3 and 10 carbon atoms per ring and optionally substituted with R; an alkaryl or aralkyl group containing between 1 and 30 carbon atoms, the terms aryl and alkyl having the above definitions; an alkoxyalkyl, alkylthioalkyl, alkylsulphonylalkyl or alkylaminoalkyl group containing between 1 and 30 carbon atoms, in a linear or branched chain; one or more heterocyclic groups containing between 5 and 10 carbon atoms per cycle; or a combination of one or more groups above, said groups being optionally substituted with R, with one or more nitro, cyano, hydroxy, carboxy, carbonyl or amino groups, with one or more halogens or with one or more nitrile functions, cyanhydrin, aldehyde, and, in the case where R and R 'together form a ring, this ring is as defined above, from the corresponding cyanohydrin of general formula (II) wherein R is and R 'are as defined above, process according to which ammoniacal hydrolysis (1) of (II) is carried out, characterized in that: (a) the hydrolysis (1) is carried out in the aqueous phase; continuously and without isolating intermediate products, at a temperature not exceeding 250 C, starting from a molar ratio NH3 / (II) of between 5 and 50, and a molar proportion of CO2 / (11) between 1 and 10, to obtain an exit mixture (5) mainly comprising the amino acid (I), dissolved carbon dioxide and ammonia, and products derived from (II); (b) products derived from (II), carbon dioxide and ammonia are recycled to hydrolysis (a).   2. Method according to claim 1, characterized in that the hydrolysis is ammoniacal (1) without catalyst.   3. Method according to claim 1 or 2, characterized in that before step (b), the output mixture (5) is expanded (6), and the expanded output mixture is separated into a stream (10). (12) Amino acid-enriched liquid (I), and a gaseous stream (11) enriched with ammonia and carbon dioxide.   4. Method according to claim 3, characterized in that separates (40) the stream (12) enriched liquid amino acid (I), amino acid (I) solid (41), discharged, and mother liquor ( 48) depleted in amino acid (I) and containing said unreacted derivatives, said mother liquors (48) being recycled, after raising (49) of their pressure to the hydrolysis (a).   5. Method according to the preceding claim, characterized in that separating the stream (12) enriched amino acid (I) by staged crystallization (45) to obtain the amino acid (I) solid, filtered (46) then dried (47), and the mother liquors (48).   6. Process according to any one of claims 3 to 5, characterized in that after condensation, the stream (22) enriched with ammonia and carbon dioxide is stored (20) and recycled (3) to the hydrolysis (a), after lifting (7) of its pressure.   7. Method according to any one of the preceding claims, characterized in that the hydrolysis (1), according to step (a), is carried out at a temperature ranging between 20 and 200 C.   8. Process according to any one of the preceding claims, characterized in that the hydrolysis (1), according to step (a), is carried out at a pressure of between 5 and 100 bar.   9. Process according to any one of the preceding claims, characterized in that the hydrolysis is carried out (a) in the presence of hydrocyanic acid, present in a molar proportion HCN / (II) not exceeding 0.1. .   10. Process according to any one of the preceding claims, characterized in that the hydrolysis (1) according to (a) is carried out, or in a tubular reactor, or in a plurality of stirred reactors (la, lb, 1c , Id), arranged in series.