WO1996035662A1 - Process for producing alkylenediaminediorganic acid and salts thereof - Google Patents

Abstract

A process for producing an alkylenediaminediorganic acid and salts thereof which comprises conducting a reaction between two organic acids selected from the group consisting of amino acids, derivatives thereof, taurine and derivatives thereof and a bifunctional compound selected from the group consisting of aldehyde compounds, acetal derivatives thereof, dihaloalkanes, derivatives thereof and epichlorohydrin under alkaline conditions.

Description

 Description Process for producing alkylenediamine diorganic acids and salts thereof

 The present invention relates to a method for producing an alkylenediamine diorganic acid and a salt thereof using an amino acid as a raw material. The alkylenediamine diorganic acids and salts thereof are widely used for applications such as detergent compositions, detergent builders, heavy metal sequestering agents, and peroxide stabilizers.

Background art

 Various chelate compounds have been used in the above applications. For example, sodium tripolyphosphate has an excellent chelating ability and has been used in detergent builders, but because it contains phosphorus, its release into the environment is a contributing factor in the eutrophication of rivers and lakes. And is not currently used. Zeolite is used as one of the currently used detergent builders.The chelating power is weak.In addition, since it is an inorganic substance, it does not have biodegradability.Because zeolite after use is insoluble in water, drain pipes etc. There is a problem such as sticking to.

 On the other hand, chelating compounds having sufficient chelating ability include amine polycarboxylic acids, and representative examples thereof include ethylenediaminetetraacetic acid (EDTA) and nitrile triacetic acid (NTA). EDTA has an extremely stable chelating power and is widely used at present.However, when released into the environment due to poor biodegradability, EDTA solubilizes heavy metals harmful to living organisms. It is feared that it will accumulate inside. In addition, although NTA has biodegradability, it is suspected to be teratogenic, and it has been reported that its iron complex has carcinogenic properties.

Ethylenediaminedisuccinic acid (EDDS) and propanediaminedisuccinic acid (PDDS) are known as amine polycarboxylic acids having both practical chelating power and biodegradability. These disuccinic compounds have two asymmetric carbon atoms and have three types of optical isomers. Several methods for producing these disuccinic acid compounds have been conventionally known. For example, as a method for producing racemic ethylenediaminedisuccinic acid, a method comprising adding two molecules of maleic acid to one molecule of ethylenediamine (Zhurnal Obshchei Khini, Vol. 49, p. 659, 1978) ) It has been known. One method for producing S, S-ethylenediaminedisuccinic acid, which is one of the optically active substances, is a method comprising adding two molecules of S-aspartic acid to one molecule of dibromoethane ( Inorganic Chemistry, Vol. 7, pp. 2405, 1968), or a method comprising adding two molecules of S-aspartic acid to one molecule of dichloroethane (Chm. Zvest i, Vol. 20, p. 414). , 1966).

 Racemic ethylenediaminedisuccinic acid obtained by a conventional method comprising reacting maleic acid with ethylenediamine has three types of isomers as described above. Of the isomers, the S and S isomers have excellent biodegradability, but the S and S isomers account for only 25% of the total racemate, and the R and S They are present in larger amounts than S, S-forms. If R and R are poorly biodegradable and are released in large quantities into the environment, there is a concern that heavy metals may accumulate in the environment, similar to ethylenediaminetetraacetic acid. The biodegradation rate of the R and S forms is slower than that of the S and S forms, and it is difficult to say that biodegradation is easy.

 The conventional method of adding S-aspartic acid to dibromoethane is strongly reported that the yield of S, S-ethylenediaminedisuccinic acid obtained is as low as 25%. It is hardly practical for a manufacturing method. The conventional method consisting of adding S-aspartic acid to dichloroethane is less reactive than the above-mentioned method using dibromoethane, and only traces of the desired S, S-ethylenediaminedisuccinic acid can be obtained.

Disclosure of the invention

The present invention provides an industrially advantageous method for producing an optically active substance, for example, an alkylenediamine diorganic acid such as S, S-ethylenediaminedisuccinic acid and S, S-propanediaminedisuccinic acid. More specifically, an object is to produce an alkylenediamine diorganic acid with high yield and high purity using an amino acid or the like as a raw material. The present inventors have conducted intensive studies to solve the above-mentioned problems. As a result, (1) condensing a compound having an aldehyde group with two molecules of amino acids and then reducing the obtained Schiff base, (2) The present inventors have found that an alkylenediamine diorganic acid can be obtained in high yield and high purity by reacting a dihaloalkane derivative or epichlorohydrin with two amino acids or the like in the presence of a metal ion, and reached the present invention.

 The present invention relates to a method for producing an S, S-form alkylenediamine diorganic acid and a salt thereof in high yield and high purity by using an S-form amino acid as a raw material.

 The present invention relates to a method for producing a Schiff base by condensing a compound having an aldehyde group on two amino acids or an acetal derivative thereof under an alkaline condition in the presence of a specific organic solvent, and then forming a metal hydride or a catalyst. The present invention relates to a method for producing an S, S-form alkylenediamine diorganic acid and a salt thereof by catalytic hydrogenation in the presence of a compound (hereinafter referred to as a first method)

 In addition, the present invention relates to an S, S-alkylenediamine diorganic acid, which is obtained by reacting two molecules of an amino acid with a dihaloalkane derivative or epichlorohydrin in the presence of an organic solvent under alkaline conditions in the presence of a metal ion. The present invention relates to a method for producing a salt. (Hereinafter, this method is called the second method.)

BEST MODE FOR CARRYING OUT THE INVENTION

 In the present invention, the organic acid is selected from the group consisting of amino acids and derivatives thereof, and taurine and derivatives thereof.

 The amino acid that can be used in the present invention may be in any form, such as solid amino acid or its metal salt or an aqueous solution of metal salt, as long as it can be used industrially.

When a solid amino acid or an alkali metal salt thereof is used, its purity is 70% or more, preferably 95%. When an aqueous solution is used, an aqueous solution of an alkali metal S-aspartate is preferably used in order to more efficiently perform a force reaction operation. The concentration of the aqueous solution of the alkali metal S-aspartate that can be used in the reaction step is 50 to 300 g ZL, preferably 100 to 260 g ZL in terms of acid. The alkali metal salt may be any of a lithium salt, a sodium salt, a potassium salt, and a rubidium salt. Industrially, sodium salts or potassium salts are used. Preferably, a sodium salt is used.

 Organic acids are glycine, N-methyldaricin, taurine, N-methyltaurine, taurine-N-acetic acid, S-aspartic acid, N-methyl-S-aspartic acid, N-methyl-S-glutamic acid, S-aspartic acid 1-N-acetic acid, S-glutamic acid 1-N-acetic acid, 1-amino-1,2,3-propanetricarboxylic acid, 2-amino-1,2,3-propanetricarboxylic acid, N-methyl_1 —Amino-1,2,3-propanetricarboxylic acid and N-methyl-1-amino-1,2,3-propanetricarboxylic acid.

 Amino acids and their derivatives include glycine, N-methylglycine, S-aspartic acid, N-methyl-S-aspartic acid, N-methyl-S-glutamic acid, S-aspartic acid-N-acetic acid, and S-glutamic acid-N- —Acetic acid, 1-amino-1,2,3-propanetricarboxylic acid, 2-amino-1,2,3-prono. Carboxylic acid, N-methyl-1-amino-1,2,3-propanetricarboxylic acid and N-methyl-1-amino-1,2,3-propanetricarboxylic acid.

 Examples of the compound having an aldehyde group used in the first method of the present invention include glioxal, chloroacetaldehyde, acrolein, methacrolein and the like. Further, acetal derivatives of the above compounds having an aldehyde group can also be used. As the compound having an aldehyde group, any of industrially available forms can be used. From the viewpoint of handling, the above compound or an aqueous solution thereof having a purity of 20 to 100% by weight is used.

When an aqueous solution of glyoxal is used as the compound having an aldehyde group, its concentration is from 20 to 50% by weight, preferably from 35 to 40% by weight. H is adjusted to 1-4, preferably 2-3. When an aqueous solution of acrolein or methacrolein is used, its concentration is 20 to 100% by weight, preferably 80 to 90% by weight. In the case of an aqueous solution of gloroacetaldehyde, the concentration is 20 to 100% by weight, preferably 40 to 60% by weight. When an aqueous solution of an acetal derivative of chloroacetaldehyde is used, the concentration is 8%. It is at least 0% by weight, preferably at least 95% by weight. As the type of acetal, dimethyl acetal, dimethyl acetal, and ethylene acetal, which can be easily adjusted and have a certain level of water solubility, are preferable.

 In the first method of the present invention, when the compound having an aldehyde group is dalioxal, a Schiff base for condensing two molecules of an amino acid or the like with one molecule of the compound having an aldehyde group under neutral to alkaline conditions is used. A production step, a Schiff base reduction step in which the reaction product, a Schiff base, is reduced by catalytic hydrogenation in the presence of a metal hydride or a catalyst, and an S, S form obtained through the reduction step. It comprises a purification step of separating and purifying alkylenediamine dicarboxylic acid and its salt.

 When the compound having an aldehyde group is chloroacetaldehyde, one molecule of chloroacetaldehyde is subjected to nucleophilic addition to the amino group of one molecule of amino acid (such as S-aspartic acid) under alkaline conditions to give 2-oxoethylamino acid. A nucleophilic addition step, and a Schiff base generation step of further dehydrating and condensing an amino group of one molecule of the amino acid with the aldehyde group of the 2-oxoethylamino acid as a reaction product. The Schiff base, which is the reaction product, is reduced to form an alkali metal salt of ethylenediamine diorganic acid (S, S-ethylenediamindisuccinic acid). It comprises a purification step of separating and purifying the S-form diamine-type biodegradable chelating agent and its salt. The nucleophilic addition step and the Schiff base group generation step may be performed continuously or stepwise.

 The amount of the amino acid used in the nucleophilic addition step is in the range of 1.8 to 2.6 times, preferably 1.9 to 2.2 times, the mole of chloroacetoaldehyde or its acetal derivative. This amount is used in order to carry out the subsequent step of generating a Schiff base continuously, so that about twice the molar amount of the amino acid with respect to chloroacetaldehyde or its acetal derivative is previously present. When the following step of generating a Schiff base is carried out in a stepwise manner, 0.8 to 6 times, preferably 0.9 to 1 mol, of chloroacetaldehyde or an acetal derivative thereof is used. It is desirable to use twice the molar amount of the amino acid.

When the compound having an aldehyde group is acrolein or methacrolein, one molecule of acrolein or methacrolein is converted to one molecule of amino acid (S-aspartic acid). Conjugate addition to the amino group of the above) under the conditions of the ionic force to produce 3-oxopropylamino acid, and the aldehyde group of the reaction product, 2-oxopropylamino acid, Furthermore, a Schiff base generation step of dehydrating and condensing the amino group of one molecule of amino acid (such as S-aspartic acid), and a Schiff base reduction in which the reaction product is reduced by catalytic hydrogenation in the presence of a metal hydride or a catalyst And a purification step of separating and purifying the diamine-type biodegradable chelating agent and its salt obtained through the reduction step. The conjugate addition step and the Schiff base generation step may be performed continuously or stepwise.

 The amount of the amino acid used in the conjugate addition step is in the range of 1.8 to 2.6 moles, preferably 1.9 to 2.2 moles, relative to acrolein or methacrolein. This amount is used in order to carry out the subsequent step of generating a Schiff base continuously, so that about twice the amount of amino acid relative to acrolein or methacrolein is previously present. When the subsequent step of generating a Schiff base is carried out stepwise, 0.8 to 1.6 times the amount of acrolein or methacrolein, preferably 0.9 to 1.2 times the molar amount of acrolein or methacrolein. It is desirable to use amino acids. The pH in the Schiff base generation step is set to be neutral to weakly alkaline by adding an alkali metal hydroxide or an aqueous solution thereof. Lithium, sodium and potassium are used as the alkali metal, and potassium and sodium are preferably used. Instead of the alkali metal hydroxide, an amino acid alkali metal salt or an aqueous solution thereof may be used.

 The setting pH in the Schiff base generation step is appropriately selected in the range of 5 to 13, preferably 9 to 12. If the pH is more than 13, coloring due to decomposition of the compound having an aldehyde group is remarkable, while if the pH is less than 5, amino acid solubility is reduced, so that generation of Schiff bases does not proceed smoothly. . The advantage of this method is that the amino acid present in the reaction solution at a high concentration has a strong buffering action, so that it is kept almost constant during the pH step once set.

When chloroacetaldehyde is used as a raw material, the initial pH in the nucleophilic addition step is set to neutral to weak alkaline by adding an alkali metal hydroxide or an aqueous solution thereof. Lithium, sodium and potassium are used as alkali metals. Preferably, potassium and sodium are used. Instead of the alkali metal hydroxide, an amino acid alkali metal salt or an aqueous solution thereof may be used.

 As a method of mixing the raw materials in the nucleophilic addition step, a method of dropping chloroacetaldehyde or an acetal derivative thereof into an aqueous solution of an amino acid at a rate that does not accumulate in the reaction solution is most commonly employed. You. A method is also possible in which an alkaline aqueous solution of an amino acid is added dropwise to an aqueous solution of chloroacetoaldehyde or an aqueous suspension of chloroacetaldehyde acetal. The temperature of the reaction solution at the time of dropping is 0 to

The temperature is 60 ° C, preferably 0 to 50 ° C. A sharp rise in temperature during the dropping causes a significant coloration of the reaction solution, which greatly reduces the reaction yield of the desired 2-oxoethylamino acid.

 The pH in the nucleophilic addition step ranges from 7 to 13, preferably from 8 to 12. If 11 exceeds 13, chloroacetaldehyde or its acetal derivative will be significantly decomposed, and if pH is less than 7, reactivity will be significantly reduced. The pH is usually set at the same time as the dropwise addition of chloroacetaldehyde or an acetal derivative thereof, and simultaneously with the addition of an equimolar 20 to 50% by weight aqueous solution of an alkali metal hydroxide. At this time, the same alkali metal hydroxide used for setting the initial pH in the nucleophilic addition step is selected.

 The dropping and aging temperature in the nucleophilic addition step is 10 to 100 ° C, preferably 40 to 100 ° C.

It is in the range of 70 ° C. The dropping time is in the range of 1 to 24 hours, preferably 1 to 4 hours, and the aging time is in the range of 1 to 5 hours, preferably 1 to 3 hours. As described above, when chloroacetaldehyde is used in the nucleophilic addition step, 2-oxoethyl amino acid is directly produced. On the other hand, when using an acetal derivative of chloroacetaldehyde, 2-oxoethyl amino acid is first produced by deacetalizing the addition product.

The deacetalization step required when using an acetal of chloroacetaldehyde can usually be carried out continuously only by changing the reaction solution PH after the nucleophilic addition step. The pH in the deacetalization step is in the range of 2 to 6, preferably 2.5 to 5.5. For setting the pH, an aqueous solution of 10 to 100% by weight, preferably 20 to 60% by weight of sulfuric acid is used. '' Maturation in the deacetalization process The forming temperature is in the range of 10 to 100 ° C, preferably 40 to 70 ° C. The aging time is in the range of 1 to 5 hours, preferably 1 to 3 hours. '' In the deacetalization step, if the pH value of the reaction solution after aging is readjusted to the pH value immediately after the nucleophilic addition step, it is possible to shift to the next step, the Schiff base generation step. At this time, the same 20 to 50% by weight aqueous solution of an alkali metal hydroxide used for setting the initial pH in the nucleophilic addition step is used for readjustment of pH. The Schiff base generation step in the present invention is advantageously carried out continuously from the nucleophilic addition step or the deacetalization step which is the preceding step. That is, in the nucleophilic addition step and the deacetalization step, when chloroacetaldehyde or an acetal derivative thereof is reacted in the presence of about twice the molar amount of an amino acid, one more amino acid is produced after the formation of 2-year-old oxoethylamino acid. Dehydration condensation produces a Schiff base. In this continuous process, the nucleophilic addition proceeds irreversibly while the Schiff base formation is reversible, so even if the Schiff base generation might precede the nucleophilic addition, The ability of oxoethyl amino acid to generate Schiff bases.

 When the Schiff base generation step is carried out continuously from the nucleophilic addition step or the deacetalich step, the pH is in the range of 7 to 13, preferably 8 to 12. The ripening temperature ranges from 0 to 60 ° C, preferably from 0 to 50 ° C. The aging time ranges from 0 to 24 hours, preferably from 0 to 4 hours.

 It is also possible to carry out the Schiff base generation step in a stepwise manner with respect to the nucleophilic addition step or the deacetalization step. At that time, the amount of the amino acid added stepwise is 0.8 to 1.6 times mol, preferably 0.9 to 1.2 times mol based on chloroacetaldehyde or its acetal used in the nucleophilic addition step. It is. In this case, it is preferable to use an alkali metal salt of an amino acid in the range of pH 7 to 13 and preferably pH 8 to 12 in order to suppress a rapid change in pH of the reaction solution.

When the Schiff base generation step is carried out stepwise, the aging time is in the range of 2 to 24 hours, preferably 1 to 4 hours. Thus, the two-stage stepwise implementation is disadvantageous from the viewpoint of the complexity of the process and the length of aging time, but it is not suitable for isolating 2-year-old oxoethylamino acid or its alkali metal salt. Adopted accordingly. The pH in the conjugate addition step is set to be neutral to weakly alkaline by adding an alkali metal hydroxide or an aqueous solution thereof. As the alkali metal, sodium Na and K are used, and preferably Na is used. Instead of an alkali metal hydroxide, an alkali metal salt of an amino acid or an aqueous solution thereof may be used.

The set pH in the conjugate addition step is in the range of 7 to 13, preferably 8 to 12. If the pH exceeds 13, coloring due to polymerization degradation of acrolein is remarkable.On the other hand, if the pH is less than 7, the production of 3-oxopropylamino acid does not proceed smoothly due to a decrease in reactivity. As a result, the compound having an aldehyde group is decomposed by polymerization. As described above, the setting pH in the conjugate addition step is a very important factor, but the advantage of this method is that it was set once because of the strong buffering action of amino acids present in high concentrations in the reaction solution. The pH value is kept almost constant during the process. When acrolein or methacrolein is used as a raw material, as a mixing method in the conjugate addition step, a method of dropping acrolein or methacrolein into an alkaline aqueous solution of amino acid at a rate that does not accumulate in the reaction solution is most commonly used Is done. A method of dropping an alkaline aqueous solution of an amino acid into an aqueous solution of acrolein or methacrolein is also possible, but the polymerization decomposition of acrolein, which is present in a large excess in the reaction solution, may unnecessarily occur during the dropping. In the case of misalignment, heat is generated at the time of dropping. The temperature of the reaction solution at the time of dropping, 0~6 0 ^D C, preferably in the range of 0 ~5 0 ° C. The rapid rise in temperature during the dropping causes a significant coloration of the reaction solution, and the reaction yield of the desired 3-oxopropylamino acid in the conjugate addition step is greatly reduced.

 The ripening temperature in the conjugate addition step is in the range of 0 to 60 ° C, preferably 0 to 50 ° C. The aging time is in the range of 1 to 24 hours, preferably 1 to 4 hours. Attaching a cooling pipe to the reactor through dripping and maturation in the conjugate addition step to prevent loss due to vaporization of acrolein or methacolein is necessary from the viewpoint of safety in order to make the reaction proceed efficiently. preferable.

Advantageously, the step of generating a Schiff base in the present invention is carried out continuously from the conjugate addition step which is the preceding step. That is, in the conjugate addition step, when acrolein or methacrolein is reacted in the presence of about twice the molar amount of amino acid, 3-oxo is obtained. Following the formation of the propyl amino acid, another molecule of the amino acid is dehydrated and condensed to form a Schiff base. In this continuous process, conjugate addition proceeds irreversibly, whereas Schiff base formation is reversible, so even if Schiff base formation might precede conjugate addition, 3- The ability of xopropylamino acid to generate Schiff bases.

 When the Schiff base generation step is performed continuously from the conjugate addition step, the pH is in the range of 7 to 13, preferably 8 to 12. The ripening temperature ranges from 0 to 60 ° C, preferably from 0 to 50 ° C. The aging time is in the range of 0 to 24 hours, preferably 0 to 4 hours.

 It is also possible to carry out the Schiff base generation step in a stepwise manner with respect to the conjugate addition step. At this time, the amount of the amino acid added stepwise is 0.8 to 1.6 times, preferably 0.9 to 1.2 times, the mole of acrolein or methacrolein. In this case, it is preferable to use an amino acid alkali metal salt in the range of pH 7 to 13 and preferably pH 8 to 12 in order to suppress a rapid change in pH of the reaction solution.

 When the Schiff base generation step is carried out stepwise with respect to the conjugate addition step, the aging time is in the range of 2 to 24 hours, preferably 1 to 4 hours. Thus, the two-stage stepwise operation is disadvantageous from the viewpoint of the complexity of the process and the length of the aging time, but it is desirable to isolate 3-oxopropylamino acid or its metal salt. Is adopted according to the purpose.

 When glyoxal is used as the compound having an aldehyde group, the above-described nucleophilic addition step is unnecessary, and the thick base generating step can be directly performed to synthesize an ethylenediamine-type chelating agent.

As a mixing method in the Schiff base generation step, a method of dropping glyoxal into a neutral to alkaline aqueous solution of amino acid, and a method of dropping a neutral to alkaline aqueous solution of amino acid into glyoxal The method is adopted, but in each case, heat is generated at the time of dropping. The temperature of the reaction solution at the time of dropping, 0~5 0 ° C, preferably 0 to 3 0 ^D C, more preferably it is desirable that the control in the range of 0 to 1 0 ° C. The rapid rise in temperature during dropping causes the reaction solution to be markedly colored, which may cause the This causes a serious decrease in yield.

 The hydrogenation reaction carried out in the Schiff base reduction step in the present invention is carried out by a catalytic hydrogenation reaction using a catalyst or a reduction reaction with a metal hydride.

As a catalyst used in the catalytic hydrogenation reaction in the Schiff base reduction step, a heterogeneous catalyst of a heavy metal such as Nigel, palladium, rhodium, ruthenium, or platinum is used. Of these, nickel is the best in terms of reactivity and availability of raw materials, and is used as Raney Ni. Further, the although other can be used for heavy metal availability standpoint of raw material, P d- (:, R h- C, R h - A 1 2 0 3, as such P t 0 _2, recovery and reuse It is desirable to do.

 The amount of the catalyst used in the catalytic hydrogenation reaction in the Schiff base reduction step is 1 to 30 mol%, preferably 5 to 10 mol%, based on the compound having an aldehyde group used in the Schiff base generation step. is there.

 The catalytic hydrogenation reaction in the Schiff base reduction step is started by adding a catalyst directly to the reaction product after the Schiff base generation step and stirring vigorously under a hydrogen atmosphere. The hydrogen pressure ranges from 0 to 100 atm, preferably from 20 to 50 atm.

 The reaction temperature in the catalytic hydrogenation reaction in the Schiff base reduction step is in the range of 20 to 100 ° C, preferably 40 to 70 ° C. The aging time ranges from 1 to 24 hours, preferably from 2 to 5 hours. After the reaction, the used catalyst is quickly filtered by gradient filtration after standing sedimentation or by filtration using a filtering agent such as celite.The separated catalyst is washed and activated. The power to be recycled <desirable.

 The filtrate obtained is a colorless or slightly brownish, slightly viscous, transparent liquid that can be used directly in the subsequent evaporation to dryness or acid precipitation crystallization steps.

 In the evaporating and drying step of the present invention, the catalytic hydrogenation reaction is carried out in the Schiff base reduction step, and when the reaction yield is high, the desired alkali metal salt of alkylenediamine diorganic acid can be directly obtained when the reaction yield is high. The purpose is to obtain.

The evaporating and drying step of the present invention is obtained by subjecting a slurry obtained by heating and concentrating the reaction product after the Schiff base reduction step by catalytic hydrogenation reaction to powder crystallization by a spray drying method. At that time, prior to heat concentration, an aqueous solution of alkali metal hydroxide is added to the reaction product after the Schiff base reduction step, and the pH is adjusted appropriately. Thereby, 2 to 4 alkali metal salts of alkylenediamine diorganic acids can be produced.

 Next, a case where a reduction reaction with a metal hydride is performed in the Schiff base reduction step of the present invention will be described.

Examples of the metal hydride used in the Schiff base reduction step include NaBH ₃ CN, Na BH ₄ , and NaH ₂ PO ₂ , and the set pH at the time of the reaction is different. When NaBH ₃ CN is used, the set pH is 5 to 12, preferably 5 to 7. When NaBKh is used, the set pH is 9 to 13, preferably 10 to 12. In the case of using a NaH ₂ P0 _2, setting the pH 8 to 1 3, preferably 1 0 to 1 2. Regardless of the type of metal hydride used, the higher the alkaline force, the higher the reduction potential and the higher the reactivity, but if the alkaline conditions are too strong, the generation of by-products and coloring will increase. Performing the reaction outside of the set pH range should be avoided, as it will result in severe yield loss when obtaining the desired product later. The reaction temperature in the Schiff base reduction step using a metal hydride is in the range of 0 to 100 ° C, preferably 20 to 50 ° C. The aging time ranges from 1 to 36 hours, preferably from 4 to 8 hours. The resulting reaction solution is a yellow-brown or brown-colored liquid, and is used directly in the subsequent acid precipitation crystallization step.

 The acid precipitation crystallization step in the present invention is achieved by adding a mineral acid to the reaction solution obtained after the Schiff base reduction step. Examples of the mineral acid used include sulfuric acid, hydrochloric acid, and nitric acid. Particularly, sulfuric acid is preferably used. The sulfuric acid is selected from industrially available ones having a purity of 60 to 98%, and the reaction solution obtained by the hydrolysis step is subjected to PH I. 0 to 3.0, preferably 1.5 to 2.5. The required amount to adjust the volume is used. The temperature at the time of dropping sulfuric acid is in the range of 10 to 100 ° C, preferably 40 to 80 ° C, and the dropping time is in the range of 0.5 to 3 hours, preferably 1 to 2 hours.

 The alkylenediamine diorganic acid, which is the target substance, is obtained by aging the reaction product after addition of sulfuric acid at 0 to 50 ° C, preferably 10 to 40 ° C, for 0 to 72 hours, preferably 1 to 5 hours. The obtained crystals are obtained by suction filtration or centrifugal filtration.

The target crystals obtained are usually mother liquors containing a trace amount of sulfate attached to the crystal surface. If the catalytic hydrogenation reaction is used in the Schiff base reduction step, which is sufficiently pure without recrystallization except for washing with a small amount of water, it is particularly advantageous in the acid precipitation crystallization step. This means that by-products other than sodium sulfate generated by the neutralization reaction are not generated, which is a very advantageous process when considering waste liquid treatment in industrial production.

 Examples of dihaloalkanes and derivatives thereof that can be used in the method of the present invention include dichloroethane, dichloropropane, 2,3-dichlorosuccinic acid, dimethyl 2,3-dichlorosuccinate, 2,3-dichloropropionic acid, Dimethyl 2,3-dichloropropionate, 2,3-Dichloropropionitrile, 2,4-Dichloroglutaric acid, 2,4-Methyl dichloroglutanolate, Dibromoethane, Dibromopropane, 2,3-Dibromosuccinic acid , 2,3-Dimethyl succinate, 2,3-Dibromopropionic acid, 2,3-Dimethyl dimethyl dibromopropionate, 2,3-Dibromopropionitrile, 2,4-Dibromoglutaric acid, 2,4 — And methyl dipromoglutarate. Dihalothane and the like are used as raw materials having excellent availability, and 2,3-dihalosuccinic acid and the like are used as raw materials for imparting excellent chelating power to the intended alkylenediamine diorganic acid. Further, the diclo-mouth is preferred from the viewpoint of the ability to use both the dichloro-form and the dibromo-form, availability of raw materials, and wastewater treatment. The dibromo compound has excellent reactivity, and it requires special care, such as strong toxicity, which has advantages such as not necessarily requiring the addition of an organic solvent in the reaction process.

 When a dihaloalkane or a derivative thereof is used as a raw material in the method of the present invention, an amino group of an organic acid undergoes nucleophilic addition to two halide portions of the dihaloalkane.

 In the method of the present invention, epichlorohydrin can also be used to link two organic acids. Epichlorohydrin is a raw material with excellent availability and reactivity.

 When epichlorohydrin is used as a raw material, 2-hydroxy-1,3-diamine type alkylenediamine diorganic acid can be obtained.

The amount of the dihaloalkane, its derivative or epichlorohydrin used in the method of the present invention is preferably 0.5 to 10 times mol per mol of an organic acid such as an amino acid. Is 1 to 5 moles. In particular, it is excellent in reactivity, and it is desirable for the addition method to gradually add dropwise into the reaction system. When using dichloroethane, dichloropropane, etc., it is possible to use a large excess in order to improve the reaction rate. After the reaction is completed, unreacted dihaloalkane is recovered by distillation, two-phase separation, etc. It is possible to use.

 In the method of the present invention, the pH at the start of the reaction is adjusted by adding an alkali metal hydroxide or an aqueous solution thereof. Examples of the alkali metal hydroxide used include lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide and the like. Of these, sodium hydroxide or potassium hydroxide is used industrially, and preferably sodium hydroxide is used. When an alkali metal salt of an organic acid is used as the raw organic acid, the alkali metal hydroxide of the alkali metal used for adjusting the pH and the alkali metal of the alkali metal salt of the organic acid should be the same. Is preferred. Examples of the organic solvent used in the method of the present invention include ethylene glycol, ethylene glycol, triethylene glycol, propylene glycol, polyethylene glycol, diethylene glycol monoalkyl ethers, and triethanolamine. Preferably, ethylene glycol, diethylene glycol, and triethylene glycol are used.

 The effect of the organic solvent used in the present invention is as follows: dihalothane, dichloropropane, dimethyl 2,3 dihalosuccinate, dimethyl 2,3-dihalopropionate, 2,3-dihalopropionitrile, 2,4-dihaloglutaric acid, 2,3 — This is particularly noticeable when a non-polar dihaloalkane derivative such as dimethyl dihaloglutarate is used, and the reaction rate is greatly improved. When the dihaloalkane derivative has an ester group or a nitrile group, these groups give a carboxyl group by being finally hydrolyzed in the reaction.

 The amount of the organic solvent used is 5 to 40 volumes based on the aqueous solution of the alkali metal salt of the organic acid.

%, Preferably in the range of 10 to 30% by volume. These organic solvents can be recovered and reused after the reaction.

The pH of the reaction step in the method using a dihaloalkane, a derivative thereof or epichlorohydrin is in the range of 9 to 12, preferably in the range of 9.5 to 11.5. Tight control of the pH in the reaction process is crucial in terms of maintaining an adequate reaction rate and preventing unnecessary hydrolysis of dihaloalkane, its derivatives or epichlorohydrin. Reaction temperatures range from 50 to 160 ° C. It is usually carried out at 110 ° C or less at normal pressure. Reaction times range from 2 to 40 hours, preferably from 4 to 16 hours. As the reaction vessel, an atmospheric pressure reaction vessel or a pressurized reaction vessel is selected according to the boiling point of the dihaloalkane derivative or the like to be used. When shortening the reaction time, it is preferable to select a high temperature condition and carry out the reaction in a pressurized reaction vessel. When an organic solvent such as diethylene glycol is used in combination during the pressurization reaction, the amount of dihaloalkane or the like can be reduced. For example, 0.1 to 10% by volume and 0.5 to 5.0% by volume of an organic solvent are added to an aqueous alkali solution of L-aspartic acid to perform a pressurized reaction, thereby reducing the amount of dihalothane used. It can be reduced to 0.5 to 2.0 times mol, preferably 0.5 to 0.6 times mol, per 1 mol of L-aspartic acid. In this case, since the amount of residual dichloromethane at the end of the reaction is a trace amount, it can be completely removed by a simple drainage treatment such as degassing.

 The metal ions used in the method of the present invention are Fe (II), Fe (III), Cu (II), Zn (II), Ni (II), Co (II), Mn (II), A 1 (III) 重 selected from heavy metals such as C d (II) and alkaline earth metals such as Mg (II), Ca (II) and Ba (II). The chelate stability constant of the desired alkylenediamine diorganic acid varies depending on the compound, and generally tends to be larger for heavy metals and smaller for alkaline earth metals. In the method of the present invention, when an alkylene diorganic acid crystal is obtained by acid precipitation crystallization after completion of the reaction, it is preferable to use an alkaline earth metal which is easy to decompose the complex.

The metal ion used in the method of the present invention has an important meaning that the target alkylenediamine diorganic acid, which accumulates in the system as the reaction proceeds, is protected as a stable metal complex from side reactions. For example, in the reaction between dichloropropane and L-aspartic acid in the present invention, if a metal ion is not added, the target propanediamine-N, N-disuccinic acid reacts with another molecule of dichloropropane, and 3 -Hydroquinpropylpropanediamine-N, N-disuccinic acid It will be a by-product.

 The effect of addition of the metal ion used in the method of the present invention is as follows: N-methylglycine, N-methyltaurine, N-methyl-S-aspartic acid, N-methyl-S-glutamic acid, S-aspartic acid-N-monoacetic acid Amino acids or organic acids having a monosubstituted amino group such as S-glutamic acid-N-monoacetic acid, aspartic acid-N-acetic acid, and organic acids; N-methyl-11-amino-1,2,3-propanetricarboxylic acid; Glycine, taurine, S-aspartic acid, S-glutamic acid, 1-amino-1,3-amino-1,2-amino-1,2-amino-1,2-amino-1,2,3-propanetricarboxylic acid, etc. When a raw material is an amino acid or organic acid having an unsubstituted amino group, such as 2,3-propanetricarboxylic acid or 2-amino-1,2,3-propanetricarboxylic acid In addition, it causes greater suppression of side reactions. When the reaction is carried out by the method of the present invention in the absence of metal ions, for example, when producing S, S-ethylenediaminedisuccinic acid, N-2-hydroxysethyl-1-S, S-ethylenediaminedisuccinic acid is produced as a by-product Is produced in large quantities, and the yield of the desired S, S-ethylenediaminedisuccinic acid is reduced. This N-2-hydroxyethyl mono-S, S-ethylenediaminedisuccinic acid can be obtained by adding dihaloethane to S, S-ethylenediaminedisuccinic acid once formed, or by dihaloethane to the raw material aspartic acid. It is by-produced through two reaction pathways, the pathway formed by the reaction of N-2-hydroxyethyl-1-s-aspartic acid and dihalothane, which are formed by addition. By the presence of metal ions in the reaction system, N-2-hydroxyethyl monosulfonate is added to the main route of the reaction step of the present invention, i.e., the dihaloethane is added to S, S-ethylenediaminedisuccinic acid. , S-Ethylenediaminedisuccinic acid can be greatly reduced.

 A method is used in which metal ions are added to the reaction solution as various metal salts. The type of metal salt is selected from hydroxides, sulfates, hydrochlorides, nitrates, acetates, carbonates and the like, preferably hydroxides or sulfates, more preferably hydroxides. . The metal ions may be added at the same time at the start of the reaction or may be added gradually as the reaction proceeds.

After the reaction using metal ions, the reaction solution is treated with a mineral acid, Alkylenediamine diorganic acid can be obtained. The metal ion used in the reaction must be removed after the reaction and prior to the acid precipitation step. In particular, when heavy metal ions are used as metal ions, it is necessary to remove and collect the metal ions from the viewpoint of preventing pollution. However, when the purpose is to produce a heavy metal complex, a metal ion suitable for the target metal salt is selected, and after the reaction is completed, the reaction solution is concentrated to obtain the target metal salt.

 On the other hand, when an alkaline earth metal is used, the alkaline earth metal is easily desorbed from the alkylenediamine diorganic acid complex under acidic conditions, so that the alkaline earth metal is directly removed without previously removing the metal removal ion. An acid precipitation step can be performed.

 In the acid precipitation crystallization step, a mineral acid is used. The mineral acids used include sulfuric acid, hydrochloric acid, nitric acid and the like. Preferably, sulfuric acid is used. The concentration of sulfuric acid may be any commercially available concentration of 60 to 98%. In the acid precipitation step, the pH of the solution is adjusted to a range of 1.0 to 3.0, preferably to a range of 1.5 to 2.5, and the temperature at the time of adding the mineral acid is 40 to 80 °. C range. The addition time of the mineral acid is preferably 1-2 hours.

 In the acid precipitation step, after addition of the mineral acid, after aging for 0 to 72 hours, preferably for 1 to 5 hours in the range of 0 to 50 ° C, preferably 10 to 40 ° C, It can be obtained by a crystal separation operation such as suction filtration or centrifugal separation. The separated crystals are high-purity crystals that do not require any special treatment, so they are washed with a small amount of water, and then dried by warm air drying or the like to obtain high-purity alkylene diamine. Organic acids can be obtained.

 When the purpose is to produce a heavy metal complex or the like, a metal ion suitable for the target metal salt is selected, and after the reaction is completed, the reaction solution is concentrated to obtain the target metal salt.

 Next, the present invention will be described in detail with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples.

Example 1

Water (1,079 kg) was charged into an autoclave reactor equipped with a stirrer, a thermometer, a dropping funnel, and a distillation apparatus, and a 48% by weight NaOH aqueous solution (1,254 kg, 15. lkmol) was added. Then, S-aspartic acid (1,000 kg, 7.52 kmol) was continuously dissolved with stirring. A 40% by weight aqueous solution of glyoxal (533 kg, 3.67 kmol) was added to the aqueous solution of 30% by weight of sodium S-aspartate prepared in this manner, under cooling at a reaction liquid temperature of 0 to 10 ° C, and Under stirring, the solution was added dropwise over 1.5 hours. After completion of the dropwise addition, stirring was continued at a reaction solution temperature of 5 to 10 ° C for another 2.0 hours.

 A 50% by weight aqueous suspension of Raney nickel (W6, 42.0 kg, 0.37 kmol) was added to the reaction solution, and the air in the reactor was sufficiently replaced with hydrogen gas. The reactor was sealed and the hydrogen pressure was reduced to 50 atm. Then, under vigorous stirring, the temperature of the reaction solution was gradually raised from 25 ° C to 50 ° C over 1 hour, and then increased to 50 ° C. Intense stirring was continued for 5.5 hours. During this time, each time the hydrogen pressure dropped to 35 atm, hydrogen was replenished to 50 atm. After allowing the reaction mixture to cool to room temperature, the supernatant was poured on a suction filtration device. The residue was also placed on the suction filtration device, washed with water (150 kg), and the light brown filtrate (4,010 kg) was removed. Obtained. The filtrate (3,450 kg) obtained by heating and concentrating this filtrate was powder-dried at 120 ° C by a spray-dry method, and the tetrasodium salt of S, S-ethylenediaminedisuccinic acid (1,715 kg. 4.51 kmoK crude yield 123%) was obtained as pale brown powder crystals (melting point 200 ° C). As a result of HPLC analysis using a chiral column, the optical purity of the produced S, S-ethylenediaminedisuccinic acid was over 99%. The components in the crude crystals were found to be 95.0% of S, S-ethylenediaminedisuccinic acid, 4.2% of S-aspartic acid, and 0.8% of acetic acid in terms of acid weight%.

Example 2

 A hydrogenation reaction was performed using Raney nickel as a catalyst in the same manner as in Example 1 to obtain a pale brown filtrate (4,023 kg).

 To this filtrate, 98% by weight sulfuric acid (880 kg, 8.8 kmol) was added dropwise over 1.5 hours. During this time, the temperature of the reaction solution rose to 80 ° C. The reaction solution was allowed to cool to 33 ° C. again, and the precipitated S, S-ethylenediaminedisuccinic acid crystals were filtered by centrifugation. Further, it was washed twice with water (40 kg) at 20 ° C to obtain wet crystals (l, 192 g).

S, S-Ethylenediaminedisuccinic acid (1,019 kg, 3.49 kmoU, 95% yield) after blast drying is a uniform white crystal, and the S, S-ethylenediaminediamine formed as a result of HPLC analysis. The chemical and optical purity of succinic acid is 99% or more Was.

Example 3

 A Schiff base generation reaction was performed in the same manner as in Example 2.

 A suspension prepared by previously dissolving NaBHN (71 kg, 1.86 kmol) in water (425 kg) was added to this reaction solution at a reaction solution temperature of 10 ° C and stirred at 0. After 5 hours, the temperature of the reaction solution was raised to 45 ° C., and stirring was continued for 5.5 hours.

 To this reaction solution, 98% by weight sulfuric acid (1,310 kg, 13.lkmol) was added dropwise over 1.5 hours. During this time, the temperature of the reaction solution rose to 80 ° C. The reaction solution was allowed to cool to 33 ° C again, and the precipitated crystals of S, S-ethylenediaminedisuccinic acid were filtered by centrifugation. Further, it was washed twice with water (40 kg) at 20 ° C to obtain wet crystals (907 g).

S, S-Ethylenediaminedisuccinic acid (890 kg, yield of 3.05 kmol 83%) after blast drying is a homogeneous white crystal, and as a result of HPLC analysis, S, S-ethylenediaminedisuccinic acid formed The chemical purity and optical purity of each were 99% or _more.c Example 4

 Water (1,079 kg) was charged into an autoclave-type reactor equipped with a stirrer, thermometer, dropping funnel and distillation apparatus, and a 48 wt% NaOH aqueous solution (1,254 kg, 15. lkmol). Then, S-aspartic acid was added. (1,000 kg, 7.52 kmol) were continuously dissolved with stirring. An aqueous solution of 30% by weight of acid and disodium 3-aspartate prepared in this manner was added to a 50% by weight aqueous solution of chloroacetaldehyde (573 g, 3.67 kmol) and a 48% by weight aqueous solution of sodium hydroxide (306 kg, 3 kg). .67kmol) was added dropwise over 1.5 hours at a reaction temperature of 40 ° C and stirring. After completion of the dropwise addition, stirring was continued at a reaction liquid temperature of 40 to 50 ° C for another 4.5 hours.

Raney nickel (W6, 50% by weight suspension, 42 kg, 0.37 kmol) was added to the reaction mixture, and the air in the reactor was sufficiently replaced with hydrogen gas. The reactor was sealed and the hydrogen pressure was reduced to 50 atm. Then, under vigorous stirring, gradually raise the temperature of the reaction solution from 25 ° C to 75 ° C over 1 hour, and then continue vigorous stirring for 50 hours at 5.5 ° C for 5.5 hours. Was. During this time, every time the hydrogen pressure dropped to 75 atm, hydrogen was replenished to 100 atm. After allowing the reaction solution to cool to room temperature and standing, the supernatant was poured on a suction filtration device, and the residue was also placed on a suction filtration device and washed with water (150 kg) to obtain a filtrate (4, 350 kg). Was. To this filtrate, 98% by weight sulfuric acid (880 kg, 8.8 kmol) was added dropwise over 1.5 hours. During this time, the temperature of the reaction solution rose to 80 ° C. The reaction solution was allowed to cool to 33 ° C. again, and the precipitated L, L-PDDS crystals were filtered by centrifugation. Further, it was washed twice with water (40 kg) at 20 ° C to obtain wet crystals (l, 244 g).

 S, S-propanediamine disuccinic acid (l, 049 kg, 3.59 kmol, 98% yield) after blast drying was a uniform white crystal, and the S, S-propane produced as a result of HPLC analysis. Both the chemical purity and the optical purity of diamine disuccinic acid were 99% or more. C Example 5

 Water (1,079 kg) was charged into an autoclave reactor equipped with a stirrer, a thermometer, a dropping funnel and a distillation apparatus, and a 48 wt% NaOH aqueous solution (1, 254 kg, 15. lkmol), and then S-asparagine The acid (1,000 kg, 7.52 kmol) was dissolved continuously with stirring. The aqueous solution of 30% by weight of sodium sodium aspartate prepared in this manner was added to an aqueous solution of 98% by weight of chloroacetaldehyde dimethyl acetal (467 kg, 3.67 kmol) and a 48% by weight aqueous solution of sodium hydroxide (306 kg. , 3.67 kmol) was added dropwise over 1.5 hours at a reaction temperature of 40 ° C and stirring. After completion of the dropwise addition, stirring was continued at a reaction liquid temperature of 40 to 50 ° C for another 4.5 hours.

 Next, 98% by weight sulfuric acid (280 kg, 2.8 kmol) was added dropwise to this reaction solution over 0.5 hour, and stirring was continued at a reaction solution temperature of 40 to 50 ° C. for another 2.0 hours. . Subsequently, a 48% by weight aqueous sodium hydroxide solution (466 kg, 5.6 kmol) was added dropwise over 0.5 hour. Raney nickel (W6, 50% by weight suspension, 42 kg, 0.37 kmol) was added to the reaction solution, and the air in the reactor was sufficiently replaced with hydrogen gas. The reactor was then sealed and the hydrogen pressure was increased to 50 atm. Then, under vigorous stirring, raise the temperature of the reaction solution from 25 ° C to 75 ° C for 1 hour, gradually raise the temperature, and continue vigorous stirring at 50 ° C for 5.5 hours. Was. During this time, every time the hydrogen pressure dropped to 75 atm, hydrogen was replenished to 100 atm. After allowing the reaction solution to cool to room temperature and standing, the supernatant was poured on a suction filtration device, and the residue was also placed on the suction filtration device and washed with water (150 kg) to obtain a filtrate (5,055 kg).

98% by weight sulfuric acid (880 kg, 8.80 kmol) was added dropwise to the filtrate over 1.5 hours. During this time, the temperature of the reaction solution rose to 80 ° C. The reaction solution was allowed to cool to 33 ° C. again, and the precipitated S, S-propanediaminedisuccinic acid crystals were filtered by centrifugation. In addition, 20 Washing twice with water (40 kg) at ° C yielded wet crystals (1, 211 g).

 S, S-propanediaminedisuccinic acid (l, 007kg, 3.45kmol, yield 94D) after blast drying is a uniform white crystal. Both the chemical purity and the optical purity of the acid were 99% or more.

 As in Example 5, a nucleophilic addition reaction and a Schiff base generation reaction were continuously performed. A suspension prepared by previously dissolving NaBHh (43 kg, 1.13 kmol) in water (400 kg) was added to this reaction mixture at a reaction temperature of 10 ° C and stirring at 0.5 ° C. Added at time. Thereafter, the temperature of the reaction solution was raised to 45 ° C, and stirring was continued for another 5.5 hours.

 To this filtrate, 98% by weight sulfuric acid (1,540 kg, 15.4 kmol) was added dropwise over 1.5 hours. During this time, the temperature of the reaction solution rose to 80 ° C. The reaction solution was allowed to cool to 33 ° C again, and the precipitated S, S-propanediaminedisuccinic acid crystals were filtered by centrifugation. Further, it was washed twice with water (40 kg) at 20 ° C to obtain wet crystals (l, 160 g).

 S, S-propanediaminedisuccinic acid (l, 020 kg, 3.49 kmol, yield 95D) after blowing and drying is a uniform white crystal. As a result of HPLC analysis, S, S-propanediaminedisuccinic acid was generated. Both the chemical purity and the optical purity of the acid were 99% or more.

As in Example 6, a nucleophilic addition reaction and a Schiff base generation reaction were continuously performed. To the reaction solution of _{this, N a BH 4 (43kg,} 1. 13kmol) the suspension was allowed to create pre-dissolved in water (400 kg), the reaction temperature 10 ° C, under stirring, 0.5 Added at time. Thereafter, the temperature of the reaction solution was raised to 45 ° C, and stirring was continued for another 5.5 hours.

To the filtrate, 98 wt% sulfuric acid (1, 540kg, 15. 4kmol) for 1.5 hour period _c was added dropwise while the temperature of the reaction solution was heated to 80 ° C. The reaction solution was allowed to cool to 33 ° C again, and the precipitated S, S-propanediaminedisuccinic acid crystals were filtered by centrifugation. Further, it was washed twice with water (40 kg) at 20 ° C. to obtain wet crystals (l, 013 g).

S, S-propanediaminedisuccinic acid (986 kg, 3.38 kmol, 92% yield) after blast drying was uniform white crystals, and as a result of HPLC analysis, S, S-propanediaminedisuccinic acid was formed. The chemical purity and optical purity of each were 99% or more. Examples 8 to 11 Instead of 98% by weight of chloroacetaldehyde dimethyl acetal (467kg), 98% by weight of chloroacetaldehyde dodecyl acetal (571kg) or '98% by weight of chloroacetaldehyde ethylene acetal (459 kg) was used, and the same operation as in Example 5 or Example 7 was performed to obtain crystals of S, S-propanediaminedisuccinic acid. Table 1 shows the results.

 table 1

Example 1 2

 Water (1,079 kg) was charged into a autoclave-type reactor equipped with a stirrer, thermometer, dropping funnel and distillation apparatus, and a 48 wt% NaOH aqueous solution (1,254 kg, 15. lkmol) was added. Aspartic acid (1,000 kg, 7.52 kmol) was continuously dissolved with stirring. 97% by weight of acrolein (210 kg, 3.67 kmol) was added to the aqueous solution of disodium 3-aspartate (30% by weight in acid) prepared as described above at a reaction temperature of 40 ° C and stirring for 1.5%. It was dropped over time. After completion of the dropwise addition, stirring was continued at a reaction liquid temperature of 40 to 50 ° C for another 4.5 hours.

Raney nickel (W6, 50% by weight suspension, 42 kg, 0.37 kmol) was added to the reaction solution, and the air in the reactor was sufficiently replaced with hydrogen gas. The reactor was then sealed and the hydrogen pressure was increased to 50 atm. Then, under vigorous stirring, the temperature of the reaction solution was gradually increased from 25 ° C to 75 ° C over 1 hour, and then vigorous stirring was continued at 50 ° C for 5.5 hours. During this time, every time the hydrogen pressure dropped to 75 atm, hydrogen was collected to 100 atm. After allowing the reaction solution to cool to room temperature and standing, the supernatant was poured on a suction filtration device, and the residue was also placed on the suction filtration device and washed with water (150 kg) to obtain a filtrate (3,690 kg). The filtrate (2,897 kg) obtained by heating and concentrating the filtrate was powder-dried at 120 ° C by a spray drying method, and the sodium salt of S, S-propanediaminedisuccinic acid (1,593 kg) was dried. , 3.85 kmol, crude yield 105%) as pale brown powder crystals (melting point 200 ° C). As a result of HPLC analysis using a chiral column, the optical purity of the produced S, S-propanediaminedisuccinic acid was over 99%. The components in the crude crystal were 98.3% by weight of S, S-propanediaminedisuccinic acid in terms of acid and 1.7% by weight of S-aspartic acid in terms of 1.7 acid.

Example 13

 A hydrogenation reaction was performed with Raney nickel in the same manner as in Example 12 to obtain a filtrate (2,700 kg).

To the filtrate, 98 wt% sulfuric acid (1, 310kg, 13. lkmol) for 1.5 hour period _c was added dropwise while the temperature of the reaction solution was heated to 80 ° C. The reaction solution was allowed to cool to 33 ° C again, and the precipitated S, S-propanediaminedisuccinic acid crystals were filtered by centrifugation. Further, it was washed twice with water (40 kg) at 20 ° C to obtain wet crystals (l, 392 g).

 S, S-propanediaminedisuccinic acid (988 kg, 3.22 kmol, yield 88%) after blast drying was a uniform white crystal, and as a result of HPLC analysis, S, S-propanediaminedisuccinic acid was formed. Both the chemical purity and the optical purity of the acid were 99% or more. Example 14

In the same manner as in Example 13, the conjugate addition reaction and the Schiff base generation reaction were continuously performed. To this reaction _{solution, N a BH 4 (43kg,} 1. 13kmol) the suspension was allowed to create pre-dissolved in water (400 kg), the reaction mixture temperature 10 ° C, under stirring, 0.5 Added at time. Thereafter, the temperature of the reaction solution was raised to 45 ° C, and stirring was continued for another 5.5 hours.

 To this reaction solution, 98% by weight sulfuric acid (1,540 kg, 15.4 kmol) was added dropwise over 1.5 hours. During this time, the temperature of the reaction solution rose to 80 ° C. The reaction solution was allowed to cool to 33 ° C. again, and the precipitated S, S-propanediaminedisuccinic acid crystals were filtered by centrifugation. Further, it was washed twice with water (40 kg) at 20 ° C to obtain wet crystals (l, 341 g).

S, S-propanediaminedisuccinic acid (999 kg, 3.27 kniol, yield 89%) after blast drying is a homogeneous white crystal, and as a result of HPLC analysis, S, S-propanediaminedisuccinic acid was formed. Both the chemical purity and the optical purity of the acid were 99% or more. Examples 15 to 17

 The same operation as in Examples 1 to 3 was carried out except that 99% by weight methacrolein (259 kg) was used instead of 97% by weight acrolein (210 kg) to obtain S, S-2-methyl-propandiamin disuccinic acid and the same. The 4 sodium salt was obtained. Table 2 shows the results.

 Table 2

Example 18

 In a pressurized reactor equipped with a stirrer, thermometer, pH meter, dropping funnel and distillation device, water (107 kg) was charged, and 97% by weight sodium hydroxide (150 kg) and S-aspartic acid ( (500 kg) was continuously charged and dissolved. To this solution were added dichloromethane-propane (373 kg), diethylene glycol (110 kg), and a slurry of 30% by weight magnesium hydroxide (254 kg), and the pH of the reaction solution was adjusted to 11 with stirring. Next, the temperature of the liquid was raised, and distillation was started at 78 ° C. While maintaining the temperature of the reaction solution at 78 ° C. and pH 11, a 48% by weight aqueous sodium hydroxide solution (380 kg) was added with stirring over time. The progress of the reaction was monitored using HPLC, and the reaction was stopped when the raw material S-aspartic acid was consumed. To the reaction solution was added 98% by weight sulfuric acid (601 kg) to adjust the pH to 2, followed by aging at 40 ° C for 1 hour, and the precipitated crystals were separated by centrifugation. After washing the wet crystal with water, it was blow-dried at 121 ° C to obtain S, S-propanediaminedisuccinic acid (541 kg) as white crystals. As a result of HP LC analysis, the crystal was found to have a chemical purity and an optical purity of 100%. Table 3 shows the results.

Example 19

In a pressurized reactor equipped with a stirrer, thermometer, pH meter, dropping funnel and distillation device, water (107 kg) was charged, and 97% by weight sodium hydroxide (150 kg) and S-aspartic acid ( (500 kg) was continuously charged and dissolved. In this solution, 3 A 0 wt% magnesium hydroxide slurry (254 kg) was added, the pH of the reaction solution was adjusted to 11 with stirring, and then the temperature of the solution was raised to 60 ° C. While maintaining the reaction solution at a temperature of 60 ° C and a pH of 11, the stirring was continued while stirring with a 48% by weight aqueous sodium hydroxide solution (160 kg) and epichlorohydrin (305 kg). ) Were added over time. The progress of the reaction was monitored using HPLC, and when the raw material S-aspartic acid was consumed, the addition of the aqueous sodium hydroxide solution and epichlorohydrin was stopped. To this reaction solution, 98% by weight sulfuric acid (456 kg) was added to adjust the pH to 2, followed by aging at 40 ° C for 1 hour, and the precipitated crystals were separated by filtration by centrifugation. After the wet crystals were washed with water, they were blow-dried at 121 ° C. to give S, S—2-hydroxy-1,3-propanediamindisuccinic acid (575 kg) as white crystals. As a result of HPLC analysis, the crystal was found to have a chemical purity and an optical purity of 100%. Table 3 shows the results.

Example 20 to 100

 The reaction was carried out with the same stoichiometry as in Example 18 except that the starting material dihaloalkane derivative or epichlorohydrin was changed to the combination shown in Table 3. Table 3 shows the results.

Comparative Examples 1 to 8 3

 The same reactions as in Examples 18 to 100 were carried out except that the addition of diethylene glycol and magnesium hydroxide was omitted. Table 3 shows the results.

 The structure of the target alkylenediamine diamino acid in each example is shown below.

Compound of Example 18 and Comparative Example 1

C H 2 C H 2 C H 2

HOOC-CH-NH NH-CH-COOH

 I I

Compound of Example 19, Comparative Example 2

OH

II HOOC-CH-NH NH-CH-COOH

Compound of Example 20, Comparative Example 3

 HOOC COOH

CH-CH

HOOC-CH-NH NH-CH-COOH

 I I

Compound of Example 21, Comparative Example 4

 COOH I

CH ₂ CH

 I I

HOOC-CH-NH NH-CH-COOH HOOC-CH, CHc COOH Compound of Example 22, Comparative Example 5

 HOOC COOH

I I

CH-CH ₂ CH

I I HOOC-CH-NH NH-CH-COOH

II HOOC-CHs CH ₂ COOH Compound of Example 23 and Comparative Example 6

 C H 2 C H 2

 I I

HOOC-CHs NH NH-CH ₂ COOH Compound of Example 24, Comparative Example 7

II.

Compound of Example 25, Comparative Example 8

 OH

CH 2 H-CH 2 II HOOC-CHs NH NH-CH ₂ COOH Compound of Example 26 and Comparative Example 9

 HOOC COOH

CH-CH

 I I

HOOC-CH, NH NH-CH: COOH Compound of Example 27 and Comparative Example 10 COOH

CH ₂ CH

Compound of Example 28, Comparative Example 11

 HOOC COOH

I I

 I I

Compound of Example 29, Comparative Example 12

 C H 2 H 2

HOOC-CH ₂ N N-CH ₂ COOH

C H 3 H 3

Example 30, Compound of Comparative Example 3

 C Η 2 Γ 2 ^ Η 2

 I I

 I I

CH 3 CH 3 Compound of Example 31 and Comparative Example 14

OH ^ H ^— CH 2

II HOOC-CH ₂ N N-CH ₂ COOH

 I I

 H 3 H 3

Compounds of Example 32 and Comparative Example 15

 HOOC COOH

I I CH-CH

 I I

HOOC-CH ₂ N N-CH ₂ COOH

H 3 C H 3

Compounds of Example 33 and Comparative Example 16

 COOH

CH ₂ -CH

 I I

CH 3 ri 3 Compound of Example 34, Comparative Example 17

 HOOC COOH

CH-CH ₂ CH

II HOOC-CH ₂ N N-CHa COOH

C H C H

Compound of Example 35, Comparative Example 18

 C H 2 ― C H 2

 I I

HOOC-CH-N N-CH-COOH

 / I I \

HOOC-CHs CH ₃ CH ₃ CH ₂ COOH Compound of Example 36, Comparative Example 19

 C H 2 H 2 C H 2

HOOC-CH-N N-CH-COOH

HOOC-CHs CH ₃ CH ₃ CH ₂ COOH Compound of Example 37 and Comparative Example 20

 OH

I

C H 2 H- C H 2

 I I

HOOC-CH-N N-CH-COOH

 / I I \

HOOC- CH 2 CH ₃ CH, CH ₂ COOH Compound of Example 38, Comparative Example 21

 HOOC COOH

CH— CH

HOOC-CH-N N-CH-COOH

HOOC-CH2 CH ₃ CH ₃ CH ₂ COOH Compound of Example 39 and Comparative Example 22

 COOH

I

CH ₂ -CH

 I I

HOOC-CH-N N-CH-COOH

_{HOOC-CH2 CHa CH 3 CH 2} COOH Example 40, the compound of Comparative Example 23

 HOOC COOH I I

 I I HOOC-CH-N N-CH-COOH

 / I I \

HOOC— CH ₂ CH ₃ CH _?, CH ₂ COOH Example 41 Compound of Comparative Example 24

 C H ― C H 2

HOOC-CH-N N-CH-COOH

HOOC-CH ₂ CH ₂ CH ₂ CH ₂ COOH

 I I HOOC COOH

Compound of Example 42, Comparative Example 25

 C H 2 then H 2 C Η 2

 I I HOOC-CH-N N-CH-COOH

HOOC-CH2 CH ₂ CH ₂ CH ₂ COOH

 I I

HOOC COOH

Compound of Example 43, Comparative Example 26

 OH I

C H 2 D H- C H 2

 I I

HOOC-CH-N N-CH-COOH

HOOC-CH2 CH ₂ H2 CH ₂ COOH

 I!

HOOC COOH Compounds of Examples 44 and Comparative Examples 27

 HOOC COOH

CH— CH

HOOC— CH— N N-CH-COOH

HOOC-CH2 CH ₂ CH ₂ CH ₂ COOH

 I I HOOC COOH

Compounds of Examples 45 and Comparative Examples 28

 COOH I

CH ₂ CH one

 I I

HOOC— CH— N N-CH-COOH

HOOC-CH ₂ CH _Z CH ₂ CH ₂ COOH

HOOC COOH

Compounds of Example 46 and Comparative Example 29

 HOOC COOH

I I

CH-CH ₂ CH

 I I

HOOC— CH— N N-CH-COOH

HOOC-CH ₂ CH ₂ CH ₂ CH ₂ COOH

 I I

HOOC COOH

Example 47, Compound of Comparative Example 30

 I I

HOOC— CH—title CH-1 COOH

HOOC-CH2 CH ₂ CH ₂ CH ₂ -COOH Compound of Example 48, Comparative Example 31

 I I

HOOC-CH-NH NH-CH-COOH

II HOOC-CH ₂ CH ₂ CH ₂ CH ₂ -COOH

Compound of Example 49, Comparative Example 32

 OH

CH ₂ CH-CH ₂

 I I HOOC-CH-NH NH-CH-COOH

II HOOC-CH2 CH ₂ CH ₂ CH ₃ -COOH Compound of Example 50, Comparative Example 3 3

 HOOC COOH I I CH-CH

HOOC-CH-NH NH-CH-COOH

II HOOC-CH2 CH ₂ CH ₂ CH ₂ -COOH Compounds of Example 51 and Comparative Example 34

 COOH

CH ₂ CH

HOOC-CH-NH NH-CH-COOH

 I I

HOOC-CH2 CH ₂ CH _Z CH ₂ -COOH Example 52 Compound of Comparative Example 35

 HOOC COOH

CH-CH ₂ CH

HOOC-CH-NH NH-CH-COOH

HOOC-CH ₂ CH ₂ CH ₂ CH ₂ -COOH Compound of Example 53, Comparative Example 36

 n 2 H 2

HOOC-CH-N N-CH-COOH

HOOC-CH ₂ CH ₂ CH ₃ CH ₃ CH ₂ CH ₂ COOH Compound of Example 54, Comparative Example 37

 C h 2 C XI 2 C H 2

 I I HOOC-CH-N N-CH-COOH

HOOC-CH2 CH ₂ CH ₃ CH ₃ CH ₂ CH ₂ COOH Compounds of Examples 55 and Comparative Examples 38

 OH

 I

 I I.

 HOOC-CH-N N-CH-COOH

_{HOOC- CH 2 CH 2 CH;!} CH, CH 2 CH 2 COOH Compound of Example 56, Comparative Example 39

 HOOC COOH

CH-CH

HOOC-CH-N N-CH-COOH

HOOC-CHs CH ₂ CH ₃ CH ₃ CH _Z CH ₂ COOH Compound of Example 57 and Comparative Example 40

 COOH

CH ₂ -CH

HOOC-CH-N N-CH-COOH

HOOC-CH ₂ CH ₂ CH ₃ CH ₃ CH ₂ CH ₂ COOH Compound of Example 58, Comparative Example 4 1

 HOOC COOH

CH-CH ₂ CH

HOOC-CH-N N-CH-COOH

HOOC-CH2 CH ₂ CH ₃ CHa CH ₂ CH ₂ COOH Compound of Example 59 and Comparative Example 42

 I I

HOn S-CH2 CH ₂ NH NH-CH2 CH ₂ SOn H Compound of Example 60, Comparative Example 43

 C H 2 C η

_{H0 3 S - CH 2 CH 2} NH NH-CH ^ CH 2 S 0 3 H Example 61, the compound of Comparative Example 4 4

 OH

 I

 _ H 2 C H ― ri 2

 I I

_{H0 3 S- CH 2 CH 2 NH} NH-CH2 CH 2 S 0 3 H Example 6 2, the compound of Comparative Example 4 5

 HOOC COOH

CH-CH

 I I

H0 ₃ S-CHs CH ₂ NH NH-CH ₂ CH ₂ S Os H Compound of Example 63, Comparative Example 46

COOH

 I I

H0 ₃ S-CH ₂ CH ₂ NH NH-CH2 CH ₂ SO3 H Compound of Example 6 4 and Comparative Example 4 7

 HOOC COOH

CH- CH, CH

H0 ₃ S -CH ₂ CH ₂ NH NH-CH ₂ CH ₂ S 0 ₃ H Compound of Example 65, Comparative Example 48

CH ₂ one CH ₂

HOa S-CH ₂ CH ₂ NN-CH ₂ CH ₂ S0 ₃ H

 I I

C Γ13 C JT13

Compound of Example 66, Comparative Example 49

 i I

H0 ₃ S-CH2 CH ₂ N N-CH ₂ CH ₂ SO :, H

 I I

 C 3 C ΓΊ 3

Compound of Example 67, Comparative Example 50

 OH

H 2 H― H 2

HO3 S-CH ₂ CH ₂ N N-CH ₂ CH ₂ SOs H

 I I

CH ₃ CH ₃

Compound of Example 68, Comparative Example 51

 HOOC COOH

I I

CH-CH

 I I

H: i CCH 3 Compounds of Example 6 9 and Comparative Example 52

 COOH

CH ₂ -CH

 I I

HOa S-CH ₂ CH ₂ N N-CH ₂ CH ₂ SOa H

 I I

 Then rl C H

Compound of Example 70, Comparative Example 53

 HOOC COOH I I

H0 ₃ S-CH ₂ CH ₂ N N-CH ₂ CH ₂ S0 ₃ H

 I I

C H H

Example 71 Compound of Comparative Example 54

 H 2 ― C H 2

H0 ₃ S-CH ₂ CH ₂ N N-CH ₂ CH ₂ S0 ₃ H

Example 72 Compound of Comparative Example 55

 I I

H0 ₃ S-CH CH ₂ NN-CH ₂ CH ₂ S0 ₃ H

 I I

HOOC-CH ₂ CH ₂ COOH Example Ί3, Comparative Example 56 Compound of 6

 ΟΗ

CH ₂ CH-CH ₂

 I I

HOs S-CH ₂ CH ₂ N N-CH2 CH ₂ S0 ₃ H

 I I

Compound of Example 74, Comparative Example 57

 HOOC COOH

CH-CH

 I I

H0 ₃ S— CH ₂ CH ₂ N N-CH ₂ CH ₂ S0 ₃ H

 I I

HOOC-H ₂ C CH ₂ COOH

Compound of Example 75, Comparative Example 58

 COOH

CH ₂ -CH

 I I

HO3 S-CH ₂ CH ₂ N N-CH ₂ CH ₂ S0 ₃ H

II HOOC-CH2 CH ₂ COOH Compounds of Example 76 and Comparative Example 59

 HOOC COOH

CH-CH ₂ CH

H0 ₃ S-CH ₂ CH ₂ N N-CH2 CH ₂ SO3 H

 I I

Compound of Example 77, Comparative Example 60

HOOC-C-NCH2 CH ₂ N-C-COOH

 / \

Compound of Example 78, Comparative Example 61

HOOC— CH ₂ HH CH ₂ COOH

HOOC—C-NCH ₂ CH ₂ CH ₂ N—C-COOH

HOOC-CH ₂ CH ₂ COOH Compound of Example 79, Comparative Example 62

HOOC-CH ₂ H OH H CH ₂ COOH

HOOC-C-NCH2 CHCH2 N— C-COOH

HOOC— CH ₂ CH ₂ COOH Compound of Example 80, Comparative Example 63

 HOOC COOH

HOOC— CH ₂ CH-CH CH ₂ COOH

HOOC-CN NC-COOH

Example 81 1, Compound of Comparative Example 64

 COOH

 I

 \ I I /

 HOOC-C-N N-C-COOH

HOOC— CH ₂ HH CH ₂ COOH Compound of Example 82 and Comparative Example 65

 COOH COOH

I I

HOOC-CH2 CH-CH2 CH CH ₂ COOH

HOOC-C-N N-C-COOH

HOOC-CH, HH CH ₂ COOH Compound of Example 83, Comparative Example 66

HOOC-CH ₂ CH ₂ -CH ₂ CH ₂ COOH '

HOOC-C-N N— C-COOH

HOOC-CH2 CH ₃ CH ₃ CH ₂ COOH

Compound of Example 84, Comparative Example 67

HOOC-CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ COOH

HOOC-C-N N-C-COOH

HOOC-CH ₂ CH ₃ CH ₃ CH ₂ COOH

Compound of Example 85, Comparative Example 68

 OH

HOOC-CH2 CH ₂ CH-CH2 CH ₂ COOH HOOC-CN NC-COOH

HOOC-CH2 CH ₃ CH ₃ CH ₂ COOH

Compound of Example 86, Comparative Example 69

 HOOC COOH

I I

HOOC-CN NC-COOH HOOC- CH 2 CH:, CH 3 CH, COOH Compounds of Example 87 and Comparative Example 70

 COOH

HOOC-CH ₂ CH ₂ -CH CH ₂ COOH

HOOC-C-N N-C-COOH

HOOC-CH2 CH ₃ CH ₃ CH ₂ COOH Example 8 8, Comparative Example 化合物 1

 COOH COOH

I I

HOOC-CH2 CHCH2 CH CH ₂ COOH

 \ I I /

 HOOC-C-N N-C-COOH

HOOC-CH2 CHs CH ₃ CH ₂ COOH Compound of Example 89, Comparative Example 72

CH ₂ -CH ₂

HOOC-CH-NH NH-CH-COOH

 I I

HOOC-CH CH-COOH

 I I

HOOC-CH2 CH ₂ COOH Compound of Example 90 and Comparative Example 73

HOOC-CH-NH NH-CH-COOH

 I I HOOC-CH CH-COOH

 I I

Example 91 1, Compound of Comparative Example 74

 OH

CH ₂ CH-CH ₂

HOOC-CH-NH NH-CH-COOH

HOOC-CH CH-COOH

HOOC-CHs CH ₂ COOH Example 92, Comparative Example Ί 5

 HOOC COOH

I I

CH CH

I I

HOOC-CH-NH NH-CH-COOH

HOOC-CH CH-COOH

II HOOC— CH ₂ CH: COOH Compound of Example 93, Comparative Example 76

 COOH

CH ₂ CH

 I I

HOOC-CH-NH NH-CH-COOH

 I I HOOC-CH CH-COOH

II HOOC-CH ₂ CH ₂ COOH Compound of Example 94, Comparative Example 77

HOOC COOH II CH-CH ₂ CH

HOOC-CH-NH NH-CH-COOH

 I I

HOOC-CH CH-COOH

 I I

HOOC-CH ₂ CH ₂ COOH Compound of Example 95 and Comparative Example 78

 C H 2 ― C H 2

HOOC-CH-N N-CH-COOH

HOOC-CH CHa CH _{; i} CH-COOH

HOOC-CH2 CH ₂ COOH Compounds of Example 96 and Comparative Example 79

HOOC-CH-N N-CH-COOH

HOOC-CH CH ₃ CH ₃ CH-COOH

II HOOC-CH ₂ CH ₂ COOH Compound of Example 97 and Comparative Example 80

 OH

CH ₂ CH-CH ₂

HOOC-CH-N N-CH-COOH

HOOC-CH CH ₃ CH ₃ CH-COOH

 I I

Compound of Example 98, Comparative Example 81

 HOOC COOH I I

HOOC-CH-N-CH-CH- -CH-COOH

 I I I \

HOOC-CH CH ₃ CH ₃ CH-COOH

II HOOC-CH2 H COOH Compounds of Examples 9 and 9 and Comparative Example 8

 COOH

HOOC-CH-N-CH ₂ -CH-N-CH-COOH

 I I I \

HOOC-CH CH ₃ CH ₃ CH-COOH

 I I

Compound of Example 100, Comparative Example 83

HOOC COOH

HOOC-CH-N N-CH-COOH

HOOC-CH CH ₃ CH ₃ CH-COOH

HOOC-CH2 CH ₂ COOH

Table 3

Example Kind of Raw Amino Acid Raw Dihaloalkane Reaction of Desired Diamine Type Po and Derivative or Epichloroamino Acid Comparative Example Kind of Ruhydrin Yield [%] Example 94

 1 8

 S-aspartic acid 1,3-dic π mouth

Comparative Example Propane 2 1

 1

Example 9 5

 1 9

 E-chlorohydrin S-aspartate

Comparative Example 3 5

 Two

Example 8 1

 2 0

 S-aspartic acid 2,3-dichloro

Comparative Example Succinic acid 8

Three Example 8 3

twenty one

 S-aspartic acid 2,3-dichloro

Comparative Example Succinic acid 1 6 4 Example 9 8 2 2

 S-aspartic acid 2,4-dichloro

Comparative Example Glutaric acid 3 5 5 Example 9 9 2 3

 Glycine 2,4-dichloro

Comparative Example Ethane 1 0 6 Example 1 0 0 2 4

 Glycine 1,3-dichloro

Comparative Example Propane 1 6

7.

Example 9 9

twenty five

 Glycine epichlorohydrin

Comparative Example 3 8

8

Example 9 8

2 6

 Glycine 2,3-dichloro Comparative Example Succinic acid 3 4

9 Example 9 6

2 7

 Glycine 2,3-dichloro Comparative Example Propionic acid 3 3

1 0 Example 9 8 ί o

 0

 Glycine 2, 4-dichloro Comparative Example Glutaric acid 3 8

1 1 Example 9 4-

2 9

 Sanolecosin 1,2-dichloro

Comparative example ethane 5 0

1 2

Example 9 4

3 0

 Sanolecosin 1 3

Comparative Example Propane 5 2 丄

Example 9 7

3 1

 Sarcosine epichlorohydrin Comparative Example 6 3

14

Example 9 5

3 2

 Sarcosine 2,3-dichloro

Comparative Example Succinic acid 5 5

1 5 Example 9 4 ′

3 3

 Sarcosine 2,3-dichloro

Comparative Example Propionic acid 5 8 1 6

Example 9 7 3 4

 Sarcosine 2,4-dichloro

Comparative Example Glutaric acid 6 2 1 7 Example 9 6 3 5

 N-methyl-S-1,2-dichloro

Comparative Example ethane aspartate 510 8 Example 9 8 3 6

 N-methyl-S-1,3-dichloro

Comparative Example Aspartic acid Propane 3 6 1 9

Example 9 7 '

3 7

 N-methyl-S-epichlorohydrin

Comparative Example Aspartic acid 3 5

2 0

Example 9 3

3 8

 N-methyl-S-2,3-dichro mouth

Comparative Example Aspartic acid Conodic acid 3 4

twenty one

Example 9 0

3 9

 N-methyl-S-2,3-dichloro

Comparative Example Aspartic acid Propionic acid 24

2 2 Example 9 6

4 0

 N-methyl-S-2,4-dichloro

Comparative Example Aspartic acid Glutaric acid 4 2

twenty three

Example 8 7 '

4 1

 N-carboxymethyl 1,2-dichloro

Comparative Example-S-aspartic acid ethane 10 24

Example 9 3 4 2

 N-carboxymethyl 1,3-dichloro

Comparative Example -S-aspartic acid propane 1 5 2 5 Example 9 8 4 3

 N-carboxymethyl epichlorohydrin

Comparative Example-S-aspartic acid 2 5 2 6 Example 8 6 4 4

 N-carboxymethyl 2,3-dichloro

Comparative Example-S-aspartic acid Succinic acid 5 2 7

Example 8 3 ′

4 5

 N-carboxymethyl 2,3-dichloro

Comparative Example-S-aspartic acid Propionic acid 7 2 8

Example 8 1 4 6

 N-carboxymethyl 2,4-dichloro

Comparative Example-S-aspartic acid Glutaric acid 6 2 9

Example 9 6 4 7

 S-glutamic acid 1,2-dichloro

Comparative example ethane 3 7 3 0

Example 9 2 4 8

 S-glutamic acid 1,3-dichloro

Comparative Example Propane 3 3 3 1

Example 9 4

4 9

 Epichlorohydrin S-glutamate Comparative Example 2 4 3 2

Example 9 8 5 0

 S-glutamic acid 2,3-dichloro

Comparative Example Conodic acid 1 7 3 3 Example 9 6 5 1

 S-glutamic acid 2,3-dichloro

Comparative Example Propionic acid 2 2 3 4 Example 9 4 5 2

 S-glutamic acid 2,4-dichloro

Comparative Example Glutamate 3 4 3 5 Example 8 8 ′

5 3

 N-methyl-S- 1,2-dichloro

Comparative Example Glutamate ethane 5

3 6

Example 8 6

5 4

 N-methyl-S-1,3-dichloro

Comparative Example Glutamate Propane 9

3 7 Example 9 0

5 5

 N-methyl-S-epichlorohydrin

Comparative Example Glutamate 6 3

3 8 Example 8 5

5 6

 N-methyl-S-2,3-dichloromouth

Comparative Example Glutamate Conodic acid 16

3 9

Example 8 2

5 7

 N-methyl-S-2,3-dichloro

Comparative Example Glutamic acid Propionic acid 18

4 0

Example 8 9

5 8

 N-methyl-S-2,4-dichloro

Comparative Example Glutamate Glutaric acid 2 6

4 1

Example 9 2

5 9

 Taurine 1,2-dichloro

Comparative example ethane 3 1

4 2

Example 9 7

6 0

 Taurine 1,3-dichloro

Comparative Example Propane 3 3

4 3

Example 9 2

6 1

 Taurine Epichlorohydrin Comparative Example 6 6

4 4 Example 9 5-

6 2

 Taurine 2,3-dichloro

Comparative Example Succinic acid 2 8

4 5

Example 9 0

6 3

 Taurine 2,3-dichloro

Comparative Example Propionic acid 2 6

4 6 Example 9 7

6 4

 Taurine 2,4-dichloro

 Glutaric acid

Comparative Example 2 7

4 7 Example 9 2

6 5

 N-methyltaurine 1,2-dichloro

Comparative example ethane 2 3

4 8 Example 9 6

6 6

 N-methyltaurine 1,3-dichloro

Comparative Example Propane 3 1

4 9 Example 9 1 ′

6 7

 N-methyltaurine epichlorohydrin

Comparative Example 5 1 5 0

Example 9 6 6 8

 N-methyltaurine 2,3-dichloro

Comparative Example Conoic acid 3 7 5 1 Example 9 2 6 9

 N-methyltaurine 2,3-dichloro

Comparative Example Propionic acid 2 8 5 2 Example 9 9 7 0

 N-methyltaurine 2,4-dichloro

Comparative Example Glutaric acid 4 2 5 3

Example 8 7 7 1

 N-carboxymethyl 1,2-dichloro

Comparative example Taurine ethane 6 5 4 Example 8 2 ′

7 2

 N-carboxymethyl 1,3-dichloro

Comparative Example Taurine Propane 3

5 5

Example 9 4

7 3

 N-carboxymethyl epichlorohydrin

Comparative Example Taurine 4 0

5 6

Example 8 8

7 4

 N-carboxymethyl 2,3-dichloro

Comparative Example Taurine Succinic acid 1 3

5 7

Example 9 1

7 5

 N-carboxymethyl 2,3-dichloro

Comparative Example Taurine Propionic acid 16

5 8

Example 9 3

7 6

 N-carboxymethyl 2,4-dichloro

Comparative Example Taurine Glutaric acid 3 3

5 9 Example

 9 7 '

7 7 2-Amino—1,2,3-propanetri 1,2-dichloro

Comparative Example Carboxylic acid ethane 2 4 6 0

Example 9 7 7 8 2 -Amino-1,2,3-propanetri 1,3-dichloro

Comparative example Carboxylic acid Propane 2 2 6 1

Example 9 3 7 9 2-7 Mino-1,2,3-propanetrichlorohydrin

Comparative example Carboxylic acid 3 2 6 2

Example 7 0 8 0 2 -Amino-1,2,3-propanetri 2,3-dichloromethane

Comparative Example Calvinic Acid Succinic Acid 0 6 3

Example 7 6 8 1 2-7 Minnow 1,2,3-propanetri 2,3-dichloro

Comparative Example Carboxylic acid Propionic acid 0 6 4 Example 8 9 ′

8 2 2 -Amino-1,2,3-propanetri 2,4-dichloro mouth

Comparative example Carboxylic acid Glutaric acid 4 6 5

Example 9 58 3 N-methyl-2-amino-1,2,3-propanetri 1,2-dichloro

Comparative Example Carboxylic acid ethane 2 6 6

Example 9 684 N-methyl-2-amino-1, 2,3-propanetri 1,3-dichloro

Comparative Example Carboxylic acid propane 966 Example 9 9 8 5 N-methyl-2-amino-1,2,3-propanetrichlorohydrin

Comparative example Carboxylic acid 3 8 6 8

Example 9 0 8 6 N-Methyl-2-amino-1,2,3-propanetri 2,3-dichloro

Comparative Example Carboxylic acid Succinic acid 0 6 9 Example 9 2 ′

87 N-Methyl-2-amino-1,2,3-propanetri 2,3-dichloro

Comparative Example Carboxylic acid Propionic acid 0

7 0 Example 9 5

8 8 N-Methyl-2-amino-1,2,3-propanetri 2,4-dichloro

Comparative example Carboxylic acid Glutaric acid 6

7 1 Example 9 1

8 9 1-7 mino—1, 2, 3—

 Propanetri 1,2-dichloro

Comparative example Carboxylic acid ethane 14

7 2 Example 9 5

9 0 1-amino—1,2,3-propanetri 1,3-dichloro

Comparative Example Carboxylic acid Propane 20

7 3 Example 9 1

9 1 1-T-mino-1,2,3-propanetrichlorohydrin

Comparative Example Carboxylic acid 24

7 4 Example 9 5 ′

9 2 Tamino-1,2,3-propanetri 2,3-Dichro mouth

Comparative Example Carboxylic acid Succinic acid 15

7 5

Example 9 1

9 3 1-T mino—1, 2, 3—

 Propantori 2,3-dichro mouth

Comparative Example Carboxylic acid Propionic acid 1 2

7 6 Example

9 4 1-T amino - 1,2, 3-Puronoヽ⁰ down Bokuri 9 4 primary, chloro

Comparative Example Carboxylic acid Glutaric acid 2 7

7 7 Actual example, 8 "

9 5 N-Methyl-1-amino-1,2,3-propanetri 1,2-dichloro

Comparative Example Carboxylic acid ethane 4

7 8 Example 7 9

9 6 N-methyl-1-amino-1,2,3-propanetri 1,3-dichloro

Comparative Example Carboxylic acid Propane 0

7 9 Example 8 9 ′

9 7 N-methyl_1-amino-1,2,3-propanetrichlorohydrin

Comparative Example Carboxylic acid 3 2 8 0

Example 8 59 8 N-methyl-1-amino-1,2,3-propanetri 2,3-dichloro

Comparative Example Carboxylic acid Succinic acid 5 8 1

Example 8 9 9 9 N-methyl-1-amino-1,2,3-propanetri 2,3-dichloro

Comparative Example Carboxylic acid Propionic acid 382 Example 9 11 0 1 0 N-Methyl-1-amino-1,2,3-propanetri 2,4-dichloro

Comparative example Carboxylic acid Glutaric acid 1 4

8 3

Example 10 1

 In a pressurized reactor equipped with a stirrer, thermometer, PH meter, dropping funnel and distillation device, 7K (1079 kg) was charged, and a 48% by weight aqueous sodium hydroxide solution (1254 kg) and S-aspartic acid ( (1 000 kg) was continuously added and dissolved. Dichloroethane (3720 kg) and diethylene glycol (525 kg) were added to this solution, and the mixture was stirred at a temperature of 80 ° C. Under stirring, a 48% by weight aqueous solution of sodium hydroxide was added over time to adjust the pH of the reaction solution to 11. While maintaining the temperature of the reaction solution at 80 and maintaining <<< 11, ferrous sulfate heptahydrate (899 kg) was added over time. The progress of the reaction was monitored using HPLC, and when aspartic acid was consumed, dichloroethane was distilled off. 98% by weight of sulfuric acid was added to the obtained dark brown slurry to adjust the pH to 5, and then calcium acetate (510 kg) and a heavy metal coagulant (10 kg) were added. To this solution was added a 48% by weight aqueous sodium hydroxide solution to adjust the pH to 13, cooled to a temperature of 5 ° C, and left for 1 hour. The precipitated slurry was separated by filtration to obtain a yellow-red transparent solution. After 98% by weight of sulfuric acid was added to the filtrate to adjust the pH to 2, the precipitated crystals of S, S-ethylenediaminedisuccinic acid were separated by filtration. After washing with water, it was dried with hot air at 11 C to obtain S, S-ethylenediaminedisuccinic acid (897 kg) as white crystals. As a result of HP LC analysis, the crystals were found to have a purity of 100% in both optical purity and optical purity. Table 4 shows the results.

Example 102

 The same reaction as in Example 101 was carried out except that a 30% slurry of magnesium hydroxide (730 k) was used instead of ferrous sulfate heptahydrate. When 98% by weight of sulfuric acid was added to the white slurry obtained in the reaction step and the pH was adjusted to 5, a pale yellow transparent filtrate was obtained. Further, sulfuric acid was added to adjust the pH to 2, and the precipitated S, S-ethylenediaminedisuccinic acid crystals were separated by filtration, washed with water, dried with hot air at 11 ° C, and dried with S, S-ethylenediamine. Disuccinic acid (980 kg) was obtained as white crystals. As a result of HP LC analysis, the crystal was 100% in both chemical purity and optical purity. Table 4 shows the results.

Comparative Example 84

Example 102 except that the addition of 30% slurry of magnesium hydroxide was omitted. The same reaction as described above was performed. Table 4 shows the results.

Example 10 3 ~ 10 9

 The same reaction as in Example 101 was carried out using the equimolar metal salts shown in Table 4 in place of the magnesium hydroxide 30% slurry. Table 4 shows the results.

 Table 4

Metal ion: Metal ion used for the reaction

Reaction yield: Yield of the target product, S, S-ethylenediaminedisuccinic acid By-product formation rate: Formation of the byproduct, N-2-hydroxyethyl-1-S, S-ethylenediaminedisuccinic acid rate

Example 1 1 0 to 1 1 6

The same reaction as in Example 102 was performed except that diethylene glycol was not added to the reaction solution and the temperature and pressure were changed in the pressurized reaction vessel. Table 5 shows the results. Table 5

Example 1 1 7 to 1 2 3

 The same reaction as in Example 102 was performed except that the amounts of diethylene glycol and dichloroethane were changed as shown in Table 6. Table 6 shows the results.

Comparative Example 8 5 to 9 1

The same reaction as in Examples 1 1 1 to 1 2 3 was performed except that diethylene glycol was not added. Table 6 shows the results.

Table 6

Industrial applicability

 According to the method of the present invention, an alkylene diamine diorganic acid having biodegradability and excellent chelating ability can be obtained in a high yield, and a detergent composition which does not adversely affect the environment. Applicable to detergent builder, heavy metal sequestrant, peroxide stabilizer, etc.

Claims

The scope of the claims

1. Two organic acids selected from the group consisting of amino acids and derivatives thereof and taurine and derivatives thereof, and difunctional compounds selected from the group consisting of compounds having aldehyde groups and their acetal derivatives, dihaloalkanes and their derivatives, and epichlorohydrin A method for producing an alkylene diamine diorganic acid and a salt thereof, which comprises reacting a neutral compound under an alkaline condition.

 2. The compound according to claim 1, wherein a compound having an aldehyde group or an acetal derivative thereof is condensed with two molecules of an amino acid or a derivative thereof under an alkaline condition to form a Schiff base, and the Schiff base is reduced. Method.

 3. The method according to claim 1, wherein two molecules of the organic acid are reacted with a dihaloalkane, a derivative thereof, or epichlorohydrin under an alkaline condition in the presence of a metal ion in an organic solvent.

 4. Amino acids and derivatives thereof are glycine, N-methyldaricin, S-asparaginic acid, N-methyl-S-aspartic acid, N-methyl-S-glutamic acid,

S-aspartic acid mono-N-monoacetic acid, S-glutamic acid mono-N-monoacetic acid, 1-amino-1,2,3-propanetricarboxylic acid, 2-amino_1,2,3-propanetricarboxylic acid, N-methyl 3. The method according to claim 2, wherein the method is selected from the group consisting of 1-amino-1,2,3-propanetricarboxylic acid and N-methyl-2-amino-1,2,3-propanetricarboxylic acid.

 5. The organic acids are glycine, N-methylglycine, taurine, N-methyltaurine, taurine mono-N-monoacetic acid, S-aspartic acid, N-methyl-S-aspartic acid, N-methyl-S-glutamic acid, S —Aspartic acid mono-N-monoacetic acid, S-glutamic acid mono-N——acetic acid, 1-amino-1,2,3-propanetricarboxylic acid, 2-amino-1,2,3-propanetricarboxylic acid, N-methyl-1- 4. The method according to claim 3, wherein the method is selected from the group consisting of amino-1,2,3-propanetricarboxylic acid and N-methyl-2-amino-1,2,3-propanetricarboxylic acid.

 6. The method according to claim 4, wherein the amino acid is S-aspartic acid.

7. The method according to claim 5, wherein the organic acid is S-aspartic acid.

8. The method according to claim 2, wherein the compound having an aldehyde group or an acetal derivative thereof is selected from the group consisting of glioxal, acrolein, methacrolein, chloroacetaldehyde, and their acetal derivatives.

 9. The method according to claim 2, wherein the reduction is performed using a metal hydride.

 10. The method according to claim 2, wherein the reduction is carried out by catalytic hydrogenation in the presence of a catalyst.

11. When the dihaloalkane or a derivative thereof is dihaloethane, dichloropropane, 2,3-dihalosuccinic acid, dimethyl 2,3-dihalosuccinate, 2,3-dihalopropionic acid, 2,3-dimethyldihalopropionate, 2,3 4. The method according to claim 3, wherein the method is selected from the group consisting of —dihalopropionitrile, 2,4-dihaloglutaric acid and dimethyl 2,3-dihaloglutarate.

 12. The method according to claim 3, wherein the metal ion force is at least one selected from the group consisting of iron, copper, zinc, nickel, cobalt, aluminum, manganese, magnesium and magnesium.

 13. The method according to claim 3, wherein the organic solvent is at least one selected from the group consisting of ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, polyethylene glycol, diethylene glycol monoalkyl ethers, and triethanolamine.