JPH09124566A - Production of aminopolycarboxylic acid - Google Patents

Abstract

PROBLEM TO BE SOLVED: To simply obtain an aminopolycarboxylic acid, in a shortened time, useful for medical and, cosmetic preparations, as a metallic ion-screening agent in the field of photography and liquid crystal and an intermediate for an oxidizer in the field of photography in high yield in high purity by reaction of a specific nitrogen-containing compound with a cyanide compound. SOLUTION: The reaction of (A) a compound of formula I [G1 is a group of the formula: Q1 -(L1 )m -C(R1a )(R1b )-(L5 )n -(L1 and L5 are each an alkylene; R1a is an aliphatic hydrocarbon group, an aryl; R1b is H, OH, carboxyl; Q1 is CN, carboxyl; m, n are 0, 1); W<1> and W<2> are an alkylene, an arylene; D is a single bond, O, S; v is 0-3] or a compound of formula II (Q2 is Q1 ; L2 is L2 ) with (B) hydrogen cyanide, a cyanide compound or an α-hydroxynitrile compound to give the objective compound of formula III [L3 and L4 are each L1 ; G is the formula: M1 O2 C-(L1 )m -C(R1a )(R1b )n (M1 is H, a cation); M2 -M4 are each M1 ].

Description

Detailed Description of the Invention

[0001]

The present invention relates to, for example, medical and cosmetic preparations, soaps, detergents, cleaning compositions, material analysis, coating on metal materials, plating, catalysts, colloid chemistry,
The present invention relates to a process for producing an aminopolycarboxylic acid derivative which is useful as a metal ion shielding agent in the fields of photography and liquid crystals, and as an intermediate of an oxidizing agent (for example, a bleaching agent for light-sensitive materials, a reducing agent) in the field of photography.

[0002]

2. Description of the Related Art Conventionally, as a method for synthesizing a compound of this kind, as described in JP-A-5-66527 and 5-178803, ethylenediamine derivatives and α, such as halogen-substituted alkylcarboxylic acid or acrylic acid, A method of reacting a β-unsaturated carboxylic acid is known. In addition, there is also a method in which an ethylene diamine derivative is reacted with a carbonyl compound containing a nitrile or a carboxyl group to form a Schiff base, and then hydrogen reduction is performed in the presence of a catalyst to obtain the target product. However, these methods have the following problems in addition to the fact that multiple steps are required for the synthesis of the target product and the raw material is higher than hydrocyanic acid. When a halogen-substituted alkylcarboxylic acid is used and reacted at around room temperature, there is a problem that it takes a long time to complete the reaction. In addition, when the temperature is raised to shorten the reaction time, the raw material undergoes hydrolysis, and an excessive amount of the raw material is required to complete the reaction. Furthermore, the presence of a large amount of this hydrolyzate hinders the crystallization of the target substance, and there is a problem that crystallization takes time. Further, when using an α, β-unsaturated carboxylic acid such as acrylic acid, the polymerization of acrylic acid partially occurs as a side reaction, which generally complicates the reaction system and makes it difficult for the target to crystallize. is there. Further, in the reaction using a carbonyl compound containing a nitrile or a carboxyl group,
There are problems that the reactivity with the secondary amine moiety contained in the intermediate used in the present invention is low, high pressure is required, the reaction is extremely time-consuming, and the structure that can be introduced is limited.

[0003]

DISCLOSURE OF THE INVENTION The object of the present invention is to provide a compound represented by the following general formula capable of exhibiting excellent performance both as a metal masking agent and as an intermediate such as an oxidizing agent in the field of silver halide photographic light-sensitive materials. An object of the present invention is to provide a method for producing aminopolycarboxylic acids represented by (I) simply, in high yield and with high purity. General formula (I)

[0004]

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(Where G is

[0006]

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Or

[0008]

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[0009] L ₁ , L ₂ , L ₃ , L ₄ and L
Each ₅ represents an alkylene group. W ¹ and W
² represents an alkylene group, an arylene group, an aralkylene group or a divalent nitrogen-containing heterocyclic group. D represents a single bond, -O-, -S- or -N (Rw)-. R _w represents a hydrogen atom, an aliphatic hydrocarbon group, an aryl group or a heterocyclic group. v represents an integer of 0 to 3, and w represents an integer of 1 to 3. R _1a represents an aliphatic hydrocarbon group, an aryl group or a heterocyclic group. R _1b represents a hydrogen atom, a hydroxy group or a carboxyl group. Z represents a non-metal atomic group necessary for forming an aryl group or a heterocyclic group. m and n each represent 0 or 1. M ₁ , M ₂ , M ₃ and M ₄ represent a hydrogen atom or a cation. )

[0010]

As a result of earnest studies, the above object is to react a compound (A) or compound (B) having a primary or secondary amino group with hydrogen cyanide or cyanide or an α-hydroxynitrile compound. It was achieved by Compound (A)

[0011]

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Compound (B)

[0013]

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General formula (I)

[0015]

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(Wherein G ₁ is

[0017]

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Or

[0019]

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Represents the following. G is

[0021]

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Or

[0023]

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Represents L ₁ , L ₂ , L ₃ , L ₄ and L
Each ₅ represents an alkylene group. W ¹ and W
² represents an alkylene group, an arylene group, an aralkylene group or a divalent nitrogen-containing heterocyclic group. D represents a single bond, -O-, -S- or -N (Rw)-. R _w represents a hydrogen atom, an aliphatic hydrocarbon group, an aryl group or a heterocyclic group. v represents an integer of 0 to 3, and w represents an integer of 1 to 3. Q ₁ and Q ₂ represent a carboxyl group or a cyano group. R _1a represents an aliphatic hydrocarbon group, an aryl group or a heterocyclic group. R _1b represents a hydrogen atom, a hydroxy group or a carboxyl group. Z represents a non-metal atomic group necessary for forming an aryl group or a heterocyclic group. m and n each represent 0 or 1. M ₁ , M ₂ , M ₃
And M ₄ represents a hydrogen atom or a cation. )

[0025]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.
First, the compound (A), the compound (B) and the general formula (I)
The compound represented by will be described in detail below. R _1a
The aliphatic hydrocarbon group represented by is a linear, branched or cyclic alkyl group (preferably having 1 to 12 carbon atoms, more preferably 1 to 7 carbon atoms, and particularly preferably 1 to 4 carbon atoms). And, for example, methyl, ethyl, n-propyl,
iso-propyl, n-butyl, iso-butyl, tert-butyl,
Examples include n-heptyl, n-hexyl and cyclohexyl. ), Alkenyl group (preferably having 2 to 12 carbon atoms, more preferably having 2 to 6 carbon atoms, particularly preferably having 2 to 2 carbon atoms)
4 is an alkenyl group, and examples thereof include vinyl and allyl. ), An alkynyl group (preferably having 2 to 1 carbon atoms)
2, more preferably an alkynyl group having 2 to 6 carbon atoms, particularly preferably 2 to 4 carbon atoms, and examples thereof include propargyl. ).

The aliphatic hydrocarbon group represented by R _1a may have a substituent, and examples of the substituent include an aryl group (preferably having 6 to 12 carbon atoms, more preferably having 6 to 12 carbon atoms). 10, particularly preferably an aryl group having 6 to 8 carbon atoms, such as phenyl and p-methylphenyl, an amino group (preferably 0 to 20 carbon atoms, more preferably 0 to 10 carbon atoms, particularly preferably Preferably 0 to 6 carbon atoms
Is an amino group, and examples thereof include amino, methylamino, dimethylamino, and diethylamino. ), An alkoxy group (preferably an alkoxy group having 1 to 8 carbon atoms, more preferably 1 to 6 carbon atoms, and particularly preferably 1 to 4 carbon atoms, and examples thereof include methoxy and ethoxy).
Aryloxy group (preferably having 6 to 12 carbon atoms, more preferably 6 to 10 carbon atoms, and particularly preferably 6 to 8 carbon atoms)
Is an aryloxy group, and examples thereof include phenyloxy. ), An acyl group (preferably having a carbon number of 12 to 12, more preferably a carbon number of 2 to 10, particularly preferably an acyl group having a carbon number of 2 to 8, and examples thereof include acetyl), an alkoxycarbonyl group (preferably having 2 carbon atoms). To 12, more preferably 2 to 10 carbon atoms, and most preferably 2 carbon atoms.
~ 8 alkoxycarbonyl groups, such as methoxycarbonyl. ), An aryloxycarbonyl group (preferably an aryloxycarbonyl group having 7 to 20 carbon atoms, more preferably 7 to 15 carbon atoms, and particularly preferably 7 to 10 carbon atoms, for example, phenyloxycarbonyl). Acyloxy group (preferably having 2 to 12 carbon atoms, more preferably 2 to 10 carbon atoms, particularly preferably 2 to 8 carbon atoms, and examples thereof include acetoxy), acylamino group (preferably having 2 carbon atoms). -10, more preferably 2 to 6 carbon atoms,
Particularly preferred is an acylamino group having 2 to 4 carbon atoms,
For example, acetylamino can be mentioned. ), An alkoxycarbonylamino group (preferably having 2 to 12 carbon atoms, more preferably 2 to 10 carbon atoms, and particularly preferably 2 to 8 carbon atoms).
Is an alkoxycarbonylamino group, and examples thereof include methoxycarbonylamino. ), An aryloxycarbonylamino group (preferably having 7 to 20 carbon atoms, more preferably 7 to 12 carbon atoms, and particularly preferably 7 to 12 carbon atoms).
It is an aryloxycarbonylamino group of 10, and examples thereof include phenyloxycarbonylamino. ),
Sulfonylamino group (preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, particularly preferably 1 to 4 carbon atoms)
Is a sulfonylamino group, and examples thereof include methanesulfonylamino. ), A sulfamoyl group (preferably a sulfamoyl group having 0 to 10 carbon atoms, more preferably 0 to 6 carbon atoms, and particularly preferably 0 to 4 carbon atoms, and examples thereof include a sulfamoyl group and a methylsulfamoyl group). , A carbamoyl group (preferably having a carbon number of 1 to 1)
0, more preferably 1 to 6 carbon atoms, particularly preferably 1 to
4 is a carbamoyl group, and examples thereof include carbamoyl and methylcarbamoyl. ), An alkylthio group (preferably having 1 to 8 carbon atoms, more preferably 1 to 6 carbon atoms,
Particularly preferred is an alkylthio group having 1 to 4 carbon atoms,
Examples include methylthio, ethylthio and carboxymethylthio. ), An arylthio group (preferably having 6 to 20 carbon atoms, more preferably 6 to 10 carbon atoms, and particularly preferably an arylthio group having 6 to 8 carbon atoms, and examples thereof include phenylthio), and a sulfonyl group (preferably carbon). C1-8, more preferably C1-6, particularly preferably C1-4 sulfonyl groups, such as methanesulfonyl), sulfinyl groups (preferably C1-8, more preferably Is a sulfinyl group having 1 to 6 carbon atoms, particularly preferably 1 to 4 carbon atoms, and examples thereof include methanesulfinyl) and a ureido group (preferably 1 to 8 carbon atoms, more preferably 1 to 4 carbon atoms).
6, particularly preferably 1 to 4 ureido groups, and examples thereof include ureido and methylureido. ), Hydroxy group, mercapto group, halogen atom (eg, fluorine atom, chlorine atom, bromine atom, iodine atom), cyano group, sulfo group, carboxyl group, nitro group, hydroxamic acid group, heterocyclic group (eg imidazolyl, pyridyl) Is mentioned. These substituents may be further substituted. The substituent is preferably an amino group, an alkoxy group, a carboxyl group, a hydroxy group, a halogen atom, a cyano group,
A nitro group is more preferable, an alkoxy group, a carboxyl group, a hydroxy group and a halogen atom are more preferable, an alkoxy group, a carboxyl group and a hydroxy group are still more preferable, and a hydroxy group and a carboxyl group are particularly preferable.

The aliphatic hydrocarbon group represented by R _1a is preferably an alkyl group having 1 to 12 carbon atoms, more preferably an alkyl group having 1 to 7 carbon atoms, and further preferably 1 to 1 carbon atoms. 4 is an alkyl group. Specifically, methyl, ethyl, n-propyl, iso-propyl, n-butyl,
Benzyl, hydroxymethyl, carboxymethyl, 5-imidazolylmethyl are preferred, especially methyl, ethyl,
N-propyl, iso-propyl, n-butyl are preferred. R _1a
The aryl group represented by may be a single ring or may form a condensed ring with another ring, and preferably has 6 to 2 carbon atoms.
It is 0, more preferably an aryl group having 6 to 16 carbon atoms, and further preferably 6 to 12 carbon atoms. The aryl group represented by R _1a is preferably a monocyclic ring or a bicyclic ring, and examples thereof include phenyl and naphthyl, more preferably a phenyl group. The aryl group represented by R _1a may have a substituent, and examples of the substituent include those exemplified as the substituents of the aliphatic hydrocarbon represented by R _1a , and an alkyl group (preferably having a carbon number of 1 to 1). 12, more preferably 1 carbon
To 7, particularly preferably an alkyl group having 1 to 4 carbon atoms, such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, n-heptyl, n-hexyl, Examples include cyclohexyl. ), An alkenyl group (preferably an alkenyl group having 2 to 12 carbon atoms, more preferably 2 to 6 carbon atoms, and particularly preferably 2 to 4 carbon atoms, and examples thereof include vinyl and allyl) and an alkynyl group ( The number of carbon atoms is preferably 2 to 12, more preferably 2 to 6, and most preferably 2 to 6.
4 is an alkynyl group, for example, propargyl. ).

The heterocyclic group represented by R _1a is a 3- to 10-membered saturated or unsaturated heterocyclic ring containing at least one N, O or S atom, which may be a monocyclic ring. However, it may form a condensed ring with another ring. The hetero ring is preferably a 5- to 6-membered aromatic hetero ring, more preferably a 5- to 6-membered aromatic hetero ring containing a nitrogen atom, and further preferably a nitrogen atom of 1
A 5- to 6-membered aromatic heterocycle containing 2 to 2 atoms. Specific examples of the heterocycle are shown below, but hydrogen on any carbon constituting these heterocycles may be removed to form a bond. For example, pyrrolidine, piperidine,
Piperazine, morpholine, thiophene, furan, pyrrole, imidazole, pyrazole, pyridine, pyrazine,
Pyridazine, triazole, triazine, indole,
Examples thereof include indazole, purine, thiadiazole, oxadiazole, quinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, pteridine, acridine, phenanthroline, phenazine, tetrazole, thiazole and oxazole. The heterocycle is preferably pyrrole, imidazole, pyrazole, pyridine, pyrazine, pyridazine, triazole, triazine, indole, indazole, thiadiazole, oxadiazole, quinoline, phthalazine, quinoxaline, quinazoline, cinnoline, tetrazole, thiazole, oxazole, More preferably, imidazole, pyrazole, pyridine, pyrazine, indole, indazole, thiadiazole, oxadiazole, quinoline, thiazole, oxazole, even more preferably imidazole, pyridine, quinoline, particularly preferably imidazole, pyridine. is there.

The heterocyclic group represented by R _1a may have a substituent, and examples of the substituent include those listed as the substituent of the aliphatic hydrocarbon represented by R ₁ and an alkyl group (preferably An alkyl group having 1 to 12 carbon atoms, more preferably 1 to 7 carbon atoms, and particularly preferably 1 to 4 carbon atoms, such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, n-heptyl, n-hexyl and cyclohexyl), an alkenyl group (preferably having 2 to 12 carbon atoms, more preferably 2 carbon atoms).
To 6, particularly preferably an alkenyl group having 2 to 4 carbon atoms, and examples thereof include vinyl and allyl. ), An alkynyl group (preferably an alkynyl group having 2 to 12 carbon atoms, more preferably 2 to 6 carbon atoms, and particularly preferably 2 to 4 carbon atoms, and examples thereof include propargyl). R _1a is preferably an alkyl group having 1 to 7 carbon atoms or a phenyl group, and more preferably an alkyl group having 1 to 4 carbon atoms or a phenyl group. Particularly preferably, it is an alkyl group having 1 to 4 carbon atoms. R _1b is preferably a hydrogen atom.

The alkylene group represented by L ₁ , L ₂ , L ₃ , L ₄ and L ₅ may be linear, branched or cyclic, and is preferably a linear or branched alkylene group. The number of carbon atoms forming the alkylene group is preferably 1.
-10, more preferably 1-6, particularly preferably 1-4. L ₁ , L ₃ , L ₄ , and L ₅ are preferably methylene and ethylene, more preferably unsubstituted methylene and unsubstituted ethylene, and particularly preferably unsubstituted methylene. L ₂ is preferably methylene,
Ethylene, methylmethylene and ethylmethylene are more preferable, methylene, methylmethylene and ethylmethylene are more preferable, and methylene and methylmethylene are particularly preferable. Further, the alkylene group represented by L ₁ , L ₂ , L ₃ , L ₄ and L ₅ may have a substituent, and examples of the substituent include a substituent of the aliphatic hydrocarbon represented by R 1. In addition to these, alkenyl groups, alkynyl groups and the like can be mentioned.

The alkylene group represented by W ¹ and W ² may be linear, branched or cyclic, and is preferably linear or branched alkylene. The alkylene group has preferably 2 to 8 carbon atoms, more preferably 2 to 6 carbon atoms, and particularly preferably 2 to 4 carbon atoms. Examples of the alkylene group represented by W ¹ and W ² include ethylene, propylene, trimethylene, 1,2-cyclohexylene and the like, preferably ethylene, propylene, trimethylene and tetramethylene, more preferably ethylene,
It is trimethylene. The arylene group represented by W ¹ or W ² may be a single ring or may form a condensed ring with another ring, and preferably has 6 to 20 carbon atoms, and more preferably has 6 to 16 carbon atoms. , And more preferably an arylene group having 6 to 12 carbon atoms. The arylene group represented by W ¹ and W ² is preferably monocyclic or bicyclic, and examples thereof include phenylene and naphthylene, and more preferably phenylene. The aralkylene group represented by W ¹ and W ² is preferably an aralkylene group having 7 to 21 carbon atoms, more preferably 7 to 17 carbon atoms, and further preferably 7 to 13 carbon atoms, such as O-xylenyl. Is mentioned.
The divalent nitrogen-containing heterocyclic group represented by W ¹ and W ² is preferably a 5- or 6-membered heteroatom having nitrogen, and examples thereof include imidazolylene. Also,
W ¹ and W ² may have a substituent, and as the substituent,
In addition to the examples of the substituent of the aliphatic hydrocarbon represented by R ₁ , an alkenyl group, an alkynyl group and the like can be mentioned.

D is a single bond, --O--, --S--, --N (R
_w ) -represents. The aliphatic hydrocarbon group, aryl group and heterocyclic group represented by R _w have the same meaning as the aliphatic hydrocarbon group, aryl group and heterocyclic group represented by R _1a . The aliphatic hydrocarbon group, the aryl group and the heterocyclic group represented by R _w may have a substituent, and the substituent may be other than those listed as the substituent of the aliphatic hydrocarbon represented by R _1. , Alkenyl groups, alkynyl groups and the like. The substituent of R _w is preferably a carboxyl group,
A phosphono group, a hydroxy group, and a sulfo group, and more preferably a carboxyl group. R _w is preferably
It is an optionally substituted alkyl group having 1 to 8 carbon atoms (eg methyl, carboxymethyl) or an aryl group having 6 to 10 carbon atoms (eg phenyl), or a heterocyclic group having 1 to 9 carbon atoms (eg pyridyl). . v represents an integer of 0 to 3, and when v is 2 or 3, W ¹ -D may be the same or different. v is preferably 0 to 2, and 0
Alternatively, 1 is more preferable, and 0 is particularly preferable. w is 1
It represents an integer of 3, and when w is 2 or 3, W ² may be the same or different. w is preferably 1 or 2. Examples of-(W ¹ -D) _v- (W ² ) _w -include the following.

[0033]

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[0034]

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More preferably-(W ¹ -D) _v- (W ² ) _w- , ethylene, propylene, trimethylene, 2,2-
Dimethyltrimethylene is more preferable, ethylene and trimethylene are more preferable, and ethylene is particularly preferable. m and n represent 0 or 1, preferably (m, n) = (1,0), (m, n) = (0,1), (m, n)
= (0,0), and more preferably (m, n) = (1,
0) and (m, n) = (0,0). The cation represented by M ₁ , M ₂ , M ₃ and M ₄ may be an organic cation or an inorganic cation. When two or more cations are present in the same molecule, they may be different cations. Examples of the cation include alkali metals (eg Li ⁺ , Na ⁺ , K ⁺ , Cs ⁺ ), alkaline earth metals (eg Ca ²⁺ , Mg ²⁺ ), ammonium (eg ammonium, tetraethylammonium), pyridinium, phosphonium ( For example tetrabutylphosphonium,
Tetraphenylphosphonium). M ₁ , M
₂ , M ₃ and M ₄ are preferably hydrogen atoms or inorganic cations, and more preferably hydrogen atoms or alkali metal ions.

Z represents a carbon atom group necessary for forming an aryl group or a heterocyclic group. The aryl group is preferably monocyclic or bicyclic, and examples thereof include a phenyl group and a naphthyl group. Preferably it is a phenyl group.
The heterocyclic group is preferably monocyclic or bicyclic,
Examples thereof include a pyridyl group and an imidazolyl group. Preferred is a pyridyl group. The aryl group or heterocyclic group formed by Z may have a substituent, and examples thereof include those exemplified as the substituents which the aliphatic hydrocarbon group represented by R _1a may have, and an alkyl group. (Preferably having 1 to 1 carbon atoms
2, more preferably an alkyl group having 1 to 7 carbon atoms, particularly preferably 1 to 4 carbon atoms, for example, methyl, ethyl,
n-propyl, iso-propyl, n-butyl, iso-butyl,
Examples thereof include tert-butyl, n-heptyl, n-hexyl and cyclohexyl. ), An alkenyl group (preferably an alkenyl group having 2 to 12 carbon atoms, more preferably 2 to 6 carbon atoms, and particularly preferably 2 to 4 carbon atoms, and examples thereof include vinyl and allyl) and an alkynyl group ( It is preferably an alkynyl group having 2 to 12 carbon atoms, more preferably 2 to 6 carbon atoms, and particularly preferably 2 to 4 carbon atoms, and examples thereof include propargyl. The substituent is preferably an alkoxy group, an acylamino group,
Sulfonylamino group, ureido group, sulfamoyl group,
A carbamoyl group, an alkylthio group, a hydroxy group, a sulfo group, a carboxyl group, a phosphono group, a nitro group or a hydroxamic acid group, more preferably a hydroxy group,
A sulfo group, a carboxyl group or a nitro group. Particularly preferred is a carboxyl group. These groups may be substituted with similar groups. The number of substituents on the aryl group or heterocyclic group formed by Z is preferably 0.
To 2, more preferably 1 or 2, and most preferably 1. The aryl group or heterocyclic group formed by Z is preferably

[0037]

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(In the formula, Z'represents a group of non-metal atoms necessary for forming an aryl group or a heterocyclic group, and R ₂ represents a hydrogen atom or a substituent). Z'is
It represents a group of non-metal atoms necessary for forming an aryl group or a heterocyclic group. The aryl group is preferably monocyclic or bicyclic, and examples thereof include a phenyl group and a naphthyl group. Preferably it is a phenyl group. The heterocyclic group is preferably a monocyclic or bicyclic group, and examples thereof include a pyridyl group and an imidazolyl group. Preferred is a pyridyl group. The ring formed by Z ′ is preferably an aryl group, more preferably a phenyl group. The aryl group or heterocyclic group formed by Z ′ may have a substituent, and examples thereof include the substituent that the aryl group or heterocyclic group formed by Z may have.

R ₂ represents a hydrogen atom or a substituent. R
_As the substituent of ₂ , an alkyl group (preferably having a carbon number of 1 to 12, more preferably having a carbon number of 1 to 1) is exemplified in addition to the substituents which the aliphatic hydrocarbon group represented by R _1a may have. 7, particularly preferably an alkyl group having 1 to 4 carbon atoms, such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, n-heptyl, n-hexyl, cyclohexyl. And the like.), An alkenyl group (preferably having 2 to 12 carbon atoms, more preferably 2 to 6 carbon atoms, and particularly preferably 2 to 2 carbon atoms).
4 is an alkenyl group, and examples thereof include vinyl and allyl. ), An alkynyl group (preferably having 2 carbon atoms)
To 12, more preferably 2 to 6 carbon atoms, and particularly preferably 2 to 4 carbon atoms, and examples thereof include propargyl and the like. ). The substituent of R ₂ is preferably an alkoxy group, amino group, acylamino group, sulfonylamino group, ureido group, sulfamoyl group, carbamoyl group, alkylthio group, hydroxy group, sulfo group, carboxyl group, phosphono group, nitro group or hydroxam. An acid group is more preferable, a hydroxy group, a sulfo group, a carboxyl group or a nitro group is more preferable, and a carboxyl group is particularly preferable. These groups may be substituted with similar groups. General formula (I)
Of the compounds represented by the following general formula (I
A compound represented by I), (III) or (IV). General formula (II)

[0040]

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(In the formula, R ₁ ′ represents an aliphatic hydrocarbon group. The aliphatic hydrocarbon group represented by R ₁ ′ is an aliphatic hydrocarbon group represented by R _1a in formula (I). And the preferred range is also the same as that of L ₁ , L ₃ ,
L ₄ , L ₅ , W ¹ , W ² , D, v, w, M ₁ , M ₂ , M
₃ , M ₄ , m and n have the same meanings as those in formula (I), and the preferred ranges are also the same. ) General formula (III)

[0042]

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(In the formula, R ₁ ″ represents an aliphatic hydrocarbon group or an aryl group. The aliphatic hydrocarbon group and the aryl group represented by R ₁ ″ are respectively R _1a in the general formula (I). It has the same meaning as the aliphatic hydrocarbon group and the aryl group represented by, and the preferred range is also the same as L ₁ , L ₃ ,
L ₄ , L ₅ , W ¹ , W ² , D, v, w, M ₁ , M ₂ , M
₃ , M ₄ , m and n have the same meanings as those in formula (I), and the preferred ranges are also the same. L ₂ ′
Represents a linear alkylene group. ) As the carbon number of the linear alkylene group represented by L ₂ ′,
It is preferably 1 to 10, more preferably 1 to 6, and particularly preferably 1 to 4. L ₂ ′ is preferably
Methylene and ethylene, more preferably methylene. General formula (IV)

[0044]

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(In the formula, Z, R ₂ , L ₃ , L ₄ , W ¹ and W
² , D, v, w, M ₂ , M ₃ and M ₄ have the same meanings as those in formula (I) in claim 1, and the preferred ranges are also the same. L ₂ ″ represents an alkylene group. ) The alkylene group represented by L ₂ ″ is a linear or branched alkylene group. The number of carbon atoms forming the alkylene group is preferably 1 to 10, more preferably 1 to 6, and particularly preferably 1 to 4. L _{2 ″} is preferably methylene, ethylene, methylmethylene, ethylmethylene, iso-propylmethylene or n-propylmethylene, more preferably methylene, methylmethylene or ethylmethylene, particularly preferably methylene or methylmethylene. Is. Of the compounds represented by the general formulas (II), (III) and (IV), the compounds represented by the following general formulas (V), (VI) and (VII) are more preferable. General formula (V)

[0046]

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(In the formula, R ₁ ′ has the same meaning as in formula (II) and the preferable ranges are also the same. L ₃ , L ₄ and W
¹ , W ² , D, v, w, M ₁ , M ₂ , M ₃ , M ₄ and m have the same meanings as those in formula (I), respectively, and the preferred ranges are also the same. ) General formula (VI)

[0048]

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(In the formula, R _{1 ″ ″} represents an aryl group.
The aryl group represented by R _{1 ″ ″ has the same} meaning as the aryl group represented by R _1a in formula (I), and the preferred range is also the same. L ₃ , L ₄ , W ¹ , W ² , D, v,
w, M ₁ , M ₂ , M ₃ , M ₄ , m and n have the same meanings as those in formula (I), and the preferred ranges are also the same. L ₂ ′ has the same meaning as that of formula (III),
The same applies to the preferred range. ) General formula (VII)

[0050]

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(In the formula, M ₅ represents a hydrogen atom or a cation. The cation represented by M ₅ has the same meaning as the cation represented by M ₁ , M ₂ , M ₃ and M ₄ in formula (I). And the preferred range is also the same as L ₃ , L ₄ , W ¹ ,
W ² , D, v, w, M ₂ , M ₃ and M ₄ have the same meanings as those in formula (I), respectively, and the preferred ranges are also the same. L _{2 ″} has the same meaning as in formula (IV), and the preferred range is also the same. ) The following are specific examples of the compound represented by the general formula (I) that can be synthesized using the production method of the present invention, but the invention is not limited thereto.

[0052]

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[0053]

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[0054]

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[0055]

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[0056]

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[0057]

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[0058]

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[0059]

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[0060]

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[0061]

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[0062]

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[0063]

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[0064]

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[0065]

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Next, a method for producing the aminopolycarboxylic acid represented by the general formula (I) will be described. The compounds represented by the compounds (A) and (B) are described in, for example, Inorganic Chemistry Vol. 8 (No. 6) 1374.
Page (1969) (Inorganic Chemist
ry, 8 (6), 1374 (1969)). For example, the compound (A ₁ ) included in the compound (A) is a compound (C ₁ ) as shown in Scheme 1.
It is obtained by reacting with an amine compound (D) modified with a protecting group. Scheme 1

[0067]

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(Wherein R _1a , R _1b , L ₁ , L ₅ , W ¹ ,
W ² , D, m, n, v and w have the same meanings as those in formula (I). Q ₁ represents a carboxyl group or a cyano group. Y represents a hydrogen atom or a protecting group (eg, acyl group, benzyl group, etc.). X
₁ is a leaving group (for example, a halogen atom (for example, a chlorine atom,
Bromine atom, iodine atom, etc.), sulfonate group (eg, methyl sulfonate, p-toluene sulfonate, etc.)
Etc.). The compound (B ₁ ) contained in the compound (B) can be obtained by reacting the compound (C) with a diamine compound (E) having no protective group. Scheme 2

[0069]

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(Wherein R _1a , R _1b , L ₁ , L ₅ , W ¹ ,
W ² , D, m, n, v and w have the same meanings as those in formula (I). Q ₁ represents a carboxyl group or a cyano group. X ₁ is a leaving group (eg, halogen atom (eg, chlorine atom, bromine atom, iodine atom, etc.), sulfonate group (eg, methyl sulfonate,
p-toluenesulfonate) and the like). As the raw material (C), when X ₁ is a halogen atom, a commercially available compound can be used, or can be synthesized by halogenating a carboxylic acid derivative or a nitrile derivative. The halogenation can be synthesized, for example, according to the method described in Shin Jikken Kagaku Koza, Vol. 14, pp. 351-354 (Maruzen). When X ₁ is a sulfonate group,
A hydroxy derivative can be used as a raw material to apply sulfonic acid esterification of the hydroxy group.
Vol., 1793-1798 (Maruzen). When Y of the amine (D) is a hydrogen atom and (E), a commercially available compound can be used. Y
When is a protecting group, a usual method for introducing a protecting group into an amino group can be applied. For example, New Experimental Chemistry Course, Vol. 14, 25
It can be synthesized according to the method described on pages 55 to 2568 (Maruzen).

A solvent may be used for the synthesis of the compound (A ₁ ) ′, and the solvent is not limited as long as it does not participate in the reaction, and examples thereof include water, alcohol (eg, methanol, ethanol, 2-propanol, etc.), acetonitrile. , Dimethylformamide, dimethylacetamide and the like. Compound (C) is usually 0.01 relative to Compound (D).
It is used in an amount of 10 to 10 times, preferably 0.01 to 6 times, more preferably 0.01 to 2 times. Further, this reaction is preferably carried out in the presence of a base, and examples of the base include alkali (sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and the like) or tertiary amine (triethylamine and the like). The amount of the base is usually 1 to 10 times by mole with respect to (C), preferably 1 to 6 times by mole,
More preferably, it is used at 1 to 2 times the molar amount. Further, the amount of the catalyst (preferably 0.001 to 0.5 times mol, more preferably 0.01 to 0.5 times mol, still more preferably 0.01 to 0.5 times mol relative to compound (C)).
This reaction proceeds advantageously when iodide such as sodium iodide or potassium iodide (0.3 times mol) is added. The reaction is usually carried out at 0 to 100 ° C, preferably 10 to 80 ° C, more preferably 20 to 70 ° C. In the synthesis of compound (A ₁ ) (when Y is a hydrogen atom, compound (A ₁ ) ′ and (A ₁ ) are the same compound), deprotection conditions suitable for the protecting group used may be used. Yes, for example, New Experimental Chemistry Course Vol. 14, pages 25555-2568 (Maruzen)
The described method can be applied. Further, among the compounds included in the compounds (A) and (B), (A ₂ ), (A ₃ ),
The compounds represented by (B ₂ ) and (B ₃ ) are described, for example, in “Journal of the American Chemical Society” Vol. 72, pages 5357-5361 (1950) (Jo
urnal of the American Chemical Society, vol.72,5357
It can also be synthesized by referring to the method described in -5361 (1950)). That is, as shown in scheme 3, compounds (A ₂ ) and (B ₂ ) can be obtained by reacting a diamine derivative with an acrylonitrile derivative. After isolation and purification by distillation under reduced pressure, the nitrile portion is hydrolyzed with an acid or an alkali, the aqueous solution is made alkaline with a base, and ammonia generated during the hydrolysis is removed to give compounds (A ₃ ) and (B ₃ ) Can be obtained. Scheme 3

[0072]

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(In the above synthetic scheme, W ¹ , W
² , D, v, w and M ₁ have the same meanings as those in formula (I). M ₂ has the same meaning as that of formula (III). R ₄ and R ₅ represent a hydrogen atom, an aliphatic hydrocarbon group, an aryl group or a heterocyclic group. A commercially available compound can be used for the diamine derivative and the acrylonitrile derivative as the raw materials. The addition reaction of the diamine derivative and the acrylonitrile derivative can be purified by distillation by heating under reflux without a solvent. At this time,
By adjusting the addition amount of the acrylonitrile derivative, the production ratio of the compounds (A ₂ ) and (B ₂ ) can be changed, and these two can be separated by distillation. The reaction proceeds with or without a solvent. If a solvent is used, it is not limited as long as it does not participate in the reaction,
For example alcohol (eg methanol, ethanol, 2
-Propanol, butanol, etc.), ether (eg dioxane, tetrahydrofuran, etc.), dimethylformamide, dimethylacetamide, etc. Further, an acrylic acid derivative can be used instead of the acrylonitrile derivative. At this time, it is not necessary to hydrolyze the next reaction. However, since it cannot be produced by distillation, it is preferable to react with an acrylonitrile derivative.

These nitrile derivatives (A ₂ ) and (B ₂ ) can be used as they are as raw materials in the production method of the present invention, or can be hydrolyzed and used as carboxylic acid derivatives. The hydrolysis of nitrile can be carried out with reference to the above-mentioned documents. As the acid, either an inorganic acid or an organic acid can be used. For example, hydrochloric acid, nitric acid, sulfuric acid, p-toluenesulfonic acid, etc. can be mentioned. Further, as the base, an inorganic base and an organic base can be used. For example, sodium hydroxide, potassium hydroxide, sodium carbonate, triethylamine, etc. can be mentioned. As a method of removing ammonia, removal by heating or decompression may be performed. However, at this time, the pH is preferably strongly alkaline. Compound (A included in Compound (A)
₄ ) is obtained by substituting the halogen atom of the halogen-substituted aromatic derivative (F) with the diamine derivative (E) as shown in Scheme 4. Scheme 4

[0075]

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(In the formula, W ¹ , W ² , D, R ₂ , Z, v and w have the same meanings as those in formula (I). X ₂ is a leaving group (for example, a halogen atom ( For example, chlorine atom, bromine atom, iodine atom, etc.), sulfonate group (eg, methyl sulfonate, p-toluene sulfonate, etc.))) In the reaction of the halogen-substituted aromatic derivative and the diamine derivative, an alkali and a catalyst are used. It is preferable. Examples of the alkali include potassium carbonate and sodium carbonate. Examples of the catalyst include copper powder, CuCl,
CuBr, CuI, CuO, etc. are mentioned. This reaction may or may not use a solvent. When used, it is not limited as long as it does not participate in the reaction. For example, alcohol (methanol, ethanol, 2-propanol, butanol, pentanol, etc.), dioxane,
Examples thereof include dimethylformamide and dimethylacetamide. In this reaction, in addition to hydrogen cyanide and cyanide,
Compounds with carbonyl groups (aldehydes, ketones, etc.)
And a cyanion (CN ⁻ ) compound, that is, an α-hydroxynitrile compound (eg, glycolonitrile) is used.

A solvent may be used in the method of the present invention,
It does not have to be used. The solvent that can be used is not limited as long as it does not participate in the reaction, but is preferably a solvent that gives a uniform solution state. For example, water, alcohol (methanol, ethanol, 2-propanol, butanol, pentanol, etc.), ketone (acetone, methyl ethyl ketone, etc.), ester (ethyl acetate, etc.), hydrocarbon (n-hexane, etc.), ether (dioxane, tetrahydrofuran) Etc.), amide (dimethylformamide, dimethylacetamide, etc.), nitrile (acetonitrile, etc.)
Can be mentioned. Preferably, a solvent that can be dissolved in water at any ratio (methanol, ethanol,
2-propanol, acetonitrile, etc.). The ratio of mixing water and the organic solvent is arbitrary and may not be mixed. The method of the present invention is preferably carried out under basic conditions, and the pH range of the solution is preferably 7 to 14, more preferably 7 to 13, and still more preferably 8 to 12. As the base, an inorganic base and an organic base can be used. For example, alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and lithium hydroxide. Hydroxides of alkaline earth metals such as barium hydroxide and calcium hydroxide. Alkali metal carbonates such as sodium carbonate and potassium carbonate. As the organic base, tertiary amines such as triethylamine, trimethylamine and triethanolamine. Quaternary ammonium hydroxides such as tetraethylammonium hydroxide and benzyltrimethylammonium hydroxide. Examples thereof include metal alkoxides such as sodium methoxide and sodium ethoxide.

When hydrogen cyanide or a cyanide salt is used as a cyanide compound, a compound having a carbonyl (aldehydes (eg formaldehyde, acetaldehyde, propionaldehyde), ketones (acetone, methylethylketone, etc.)) is used in combination. It is preferably 1/3 to 3. Compound (A)
In order to obtain the general formula (I) by reacting with a compound having a cyano group (α-hydroxynitrile compound), -L ₂ -CO ₂ M ₂ , -L ₃ -CO ₂ M ₃ , -L _{When 4-} CO ₂ M ₄ is different from each other, different carbonyl-containing compounds to be used in combination with the nitrile group-containing compound,
It is preferable to carry out the reaction three times sequentially. However, this reaction does not necessarily mean isolation. That is,
When one reaction is completed, the next reaction can be performed in the same container. When all three are the same, it is preferable to use the compound having a nitrile group and the compound having a carbonyl in an amount of 3 times or more of the number of moles required at the time of introduction at one site, and to introduce them in one reaction. As a method of reacting the compound (B) with a compound having a cyano group to obtain the general formula (I), when -L ₃ -CO ₂ M ₃ and -L ₄ -CO ₂ M ₄ are different, Compounds having a carbonyl used in combination with the compound having a nitrile group, use different ones,
It is preferable to carry out the reaction twice, sequentially. However, this reaction does not necessarily mean isolation. That is,
When one reaction is completed, the next reaction can be performed in the same container. When both are the same, it is preferable that the compound having a nitrile group and the compound having a carbonyl be used in an amount of at least twice the number of moles required at the time of introduction at one site, and introduced in a single reaction. The amount of hydrogen cyanide or hydrocyanic acid salt used in this reaction is 0.2 to 15 mol, more preferably 1 to 10 mol, relative to 1 mol of compound (A) or compound (B) in order to introduce one carboxyl group. , And more preferably 1 to 5 mol. The amount of the compound having a carbonyl used is 0.2 to 15 mol, more preferably 1 to 10 mol, and further preferably 1 to 10 mol of the compound (A) or the compound (B) in order to introduce one carboxyl group. Is 1 to 5 mol. The number of carboxyl groups to be introduced can be adjusted by adjusting the ratio of hydrogen cyanide or cyanide salt to the compounds (A) and (B) and the compound having carbonyl. The compound having hydrogen cyanide or cyanide salt and carbonyl may be mixed and added, or may be added separately at the same time. Moreover, you may add it separately, shifting the time.
A compound having hydrogen cyanide or a cyanide salt and carbonyl may be added to the position where the compound (A) or (B) is present, or vice versa.

The reaction temperature is preferably 0 to 150.
C., more preferably 10 to 130.degree. When it is desired to obtain the nitrile derivative once, it is preferably cooled. In addition, it is preferable to remove the ammonia produced during the hydrolysis of the nitrile by reducing the pressure or heating as needed. The preferable reaction time for introducing the alkylenecarboxylic acid is 0.5 to 20 hours, more preferably 1 to 15 hours. At the end of the reaction, the target substance is dissolved in the solution in the form of salt (alkali metal salt, ammonium salt, etc.), but if the reaction liquid is cooled or concentrated and then left to stand, the target substance may precipitate as a salt. There is.
Moreover, the free acid of the target can also be obtained by adding an acid to the reaction solution to make it acidic. Examples of acids that can be used at this time include inorganic acids (for example, hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid), organic acids (acetic acid, oxalic acid, p-toluenesulfonic acid, 1,10-naphthalenedisulfonic acid, etc.) and the like. When the compound having a nitrile group is a reaction product of a compound having a carbonyl with hydrogen cyanide or a cyanide salt (for example, glycolonitrile produced by formaldehyde and hydrocyanic acid), the amount used is to introduce one carboxyl group, The amount is 0.2 to 15 mol, more preferably 1 to 10 mol, still more preferably 1 to 5 mol, per 1 mol of compound (A) or compound (B). The number of carboxyl groups to be introduced can be adjusted by adjusting the amount of the compound (A) or (B) used. The reaction time is preferably 0.1 to 20 hours, more preferably 0.5 to 15 hours for introducing the alkylenecarboxylic acid. The cyano compound formed in the reaction solution needs to be hydrolyzed to a carboxylic acid body, but as the one that can be used when hydrolyzing with an acid, an inorganic acid (for example, hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, etc.) can be used. , Organic acids (acetic acid, oxalic acid,
p-toluenesulfonic acid, 1,10-naphthalenedisulfonic acid, etc.) and the like. It may also be hydrolyzed with alkali.

[0080]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the invention is limited thereto. Example 1 Synthesis Method of Compound 34 Scheme 5

[0081]

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(Synthesis of Intermediate 34A) Ethylenediamine
170 g (2.83 mol) and 70% cis-2-pentenenitrile 328 g (2.
(83 mol) was placed in a three-necked flask, and heated under reflux for 24 hours.
Intermediate 3 was obtained by vacuum distillation (0.3mmHg, 140-150 ℃).
268 g of 4A was obtained (yield 67%). (Synthesis of Compound 34) Intermediate 34A60.0
Add g (0.270mol) and add 33.1g of sodium cyanide.
(0.675 mol) and an aqueous solution of 28.4 g (0.709 mol) of sodium hydroxide were added, and the whole was diluted with water to 200 ml. Cool the solution to below 10 ° C and stir it to 36%.
A solution prepared by diluting formalin 22.5 g (0.27 mol) to 200 ml was added dropwise over 20 hours. Then, heat to 60 ℃ and reduce the pressure to 200m.
l of water was distilled off. The reaction solution was cooled to 10 ° C or lower again, and a solution prepared by diluting 11.3 g (0.135 mol) of formalin to 100 ml was used.
It was dropped over time. As before, 100 ml of water was distilled off. While dropping formalin and distilling off water repeatedly, 0.675 mol of formaldehyde was added in total. The solution was diluted with water to 1 and 6M sulfuric acid was added over 2 hours to adjust the pH to 1.2. Further, upon stirring for 2 hours or more, crystals were precipitated. The crystals were collected by filtration, washed with a small amount of water, and dried under reduced pressure. Yield 96.5
g (yield 95%) (Comparative experiment: bromoacetic acid was used to introduce a carboxymethyl group in the above reaction) Scheme 6

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200 ml of concentrated hydrochloric acid was placed in a three-necked flask, and while cooling the container in an ice bath, 60.0 g (0.270 mol) of intermediate 34A was prepared.
l) was added dropwise over 1 hour. After dripping, 3 in a hot water bath
The mixture was heated for 10 hours, and then cooled to room temperature. After removing excess hydrochloric acid under reduced pressure, water was added to dilute the mixture to 500 ml, and the mixture was adjusted to be strongly alkaline with a 50% aqueous sodium hydroxide solution. After removing ammonia under reduced pressure, an aqueous solution of 113 g (0.81 mol) of bromoacetic acid neutralized with a 50% aqueous sodium hydroxide solution was added, and the mixture was left overnight. Activated carbon was added to the reaction solution, filtered through Celite, and then adjusted to pH 1.5 with concentrated hydrochloric acid. After desalting by electrodialysis, the solution was concentrated under reduced pressure and left overnight. The precipitated crystals were collected by filtration and washed with water. 67.0 g of the desired product was obtained by drying (yield 66%) As described above, the production method of the present invention using a compound having a cyano group is a cheaper raw material (formaldehyde, sodium cyanide) than a halogenated alkylcarboxylic acid. From the above), it is understood that it is excellent in that it can be obtained in good yield.

Example 2 Depending on the reaction conditions using the compound having a nitrile group shown in Example 1, compounds 7, 8, 10, 12,
16, 30, 35, 39, 43, 44, 59 are shown in Table 1-
When synthesized from the intermediates described in 1, 1-2, Table 1-
1, the yields shown in Table 1-2 were obtained. Table 1-1

[0086]

[Table 1]

Table 1-2

[0088]

[Table 2]

As can be seen from Table 1-1 and Table 1-2,
The target product could be obtained in high yield.

Example 3 Synthesis of Compound 6 Scheme 6

[0091]

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(Synthesis of Compound 6A) 20 g (0.33 mol) of ethylenediamine and 50 ml of water were placed in a reaction vessel, and the mixture was stirred in an ice bath for 1 hour.
The mixture was well stirred while being cooled to 0 ° C or lower. To this reaction solution, an aqueous solution of 153 g (1.00 mol) of 2-bromopropionic acid neutralized with an aqueous solution of 48% sodium hydroxide in advance was added. The mixture was stirred at room temperature for 8 hours while maintaining the pH at 8 to 11 with a 48% aqueous sodium hydroxide solution. Then p with hydrochloric acid
It was adjusted to H2 and the precipitated crystals were collected by filtration. After washing with water and acetone, heating (45 ° C) and drying, 55 g of compound 6A
(0.27 mol) was obtained. Yield 81% (Synthesis of Compound 6) 51 g of Intermediate 6A was placed in a reaction vessel.
(0.25 mol), 48% sodium hydroxide aqueous solution 43.8g (0.525mo
l) and 50.0 g of water were added, and the temperature was raised to 90 ° C. while stirring well. In this reaction liquid, 14.2 g (0.525 mol) of hydrogen cyanide
, 37% formalin 42.6 g (0.525 mol) and 48% sodium hydroxide aqueous solution 47.1 g (0.565 mol) were added dropwise at 90 ° C. over 1 hour. After the dropping, stir at 100 ° C for 2 hours and then 37
% Formalin 2 g (0.025 mol) was added to decompose residual hydrogen cyanide. Add 50% aqueous sulfuric acid to adjust the pH to 1.5.
The precipitated crystals were collected by filtration. 2/3 of target 6
76.6 g (yield 92.2%) was obtained as a hydrate. From the above results, even if the reaction temperature was raised in order to carry out the reaction promptly, the amount of by-products was small and the crystallinity of the target product did not deteriorate.
Further, the yield was improved as compared with the case where the halogenated alkylcarboxylic acid or glyoxylic acid was used.

Example 4 Depending on the reaction conditions using the compound having a cyano group shown in Example 3, compounds 1, 9, 28, 43, 4 were similarly prepared.
When 6,51 was synthesized from the intermediates shown in Table 2, the yields shown in Table 2 were obtained. Table 2

[0094]

[Table 3]

It can be seen from Table 2 that the production method of the present invention is excellent. Example 5 Synthesis of Compound 16 Scheme 7

[0096]

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(Synthesis of Intermediate 16A) Ethylenediamine
50.0 g (0.832 mol) and crotononitrile 223 g (3.328 mol)
Was placed in a three-necked flask and heated under reflux for 20 hours. Distillation under reduced pressure (0.3 mmHg, 140-150 ° C.) gave Intermediate 16A. (Synthesis of Compound 16) 48.6 of the intermediate 16A was placed in a reaction vessel.
g (0.25 mol), 48% sodium hydroxide aqueous solution 87.6g (1.05
mol) and 50.0 g of water were added, and the temperature was raised to 100 ° C. while stirring well. To this reaction liquid, 14.2 g of hydrogen cyanide (0.525 mo
l), 42.6 g (0.525 mol) of 37% formalin and 47.1 g (0.565 mol) of 48% aqueous sodium hydroxide solution were added dropwise at 100 ° C. over 1 hour. After completion of the dropping, the mixture was stirred at 100 ° C. for 2 hours, and 37% formalin (2 g, 0.025 mol) was added to decompose residual hydrogen cyanide. Add 50% sulfuric acid solution,
It was adjusted to pH 1.5 and desalted by electrodialysis. The precipitated crystals were collected by filtration. 81.0 g of Target 16 as hemihydrate
(Yield 90.7%) was obtained. In the production method of the present invention, when the intermediate has a nitrile group, it is excellent in that the hydrolysis can be performed simultaneously with the introduction of another alkylenecarboxylic acid without separately providing a hydrolysis step to the carboxyl group. There is.

Example 6 Similarly to compounds 12, 18, 29 and 3 depending on the reaction conditions using the compound having a cyano group shown in Example 5.
When 0, 34, 35 and 40 were synthesized from the intermediates shown in Table 3-1, Table 3-2, the yields shown in Table 3-1 and Table 3-2 were obtained. Table 3-1

[0099]

[Table 4]

Table 3-2

[0101]

[Table 5]

From Table 3-1 and Table 3-2, it can be seen that the production method of the present invention is excellent.

Example 7 Synthesis of Compound 63 Scheme 8

[0104]

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(Synthesis of Intermediate 63A) JP-A-5-665
27 was synthesized by the method described in Synthesis Example 1. (Synthesis of Intermediate 63B) 114 g (0.524 mol) of Intermediate 63A was suspended in 400 ml of water, and 42.0 g (1.052 mol) of sodium hydroxide / 80 ml of 80 ml of water was added dropwise at room temperature under a nitrogen atmosphere. After adding 96.0 g (0.628 mol) of α-bromopropionic acid, the mixture was heated to about 50 ° C., and 50.0 g (1.25 mol) of sodium hydroxide / 80 ml of water was added dropwise so as to keep the pH at about 10. After completion of the dropping, the reaction is continued for another 2 hours, and then cooled to room temperature,
The pH was adjusted to about 3 by adding concentrated hydrochloric acid. After standing overnight, the precipitated solid was collected by filtration, washed with water, and dried under reduced pressure to obtain 67.6 g (0.268 mol) of pale yellow solid 63B. yield
51%. (Synthesis of Compound 63 from Intermediate 63B) 63.1 g (0.25 mol) of Intermediate 63B, 43.7 g (0.525 mol) of 48% aqueous sodium hydroxide solution and 50.0 g of water were placed in a reaction vessel and stirred at 100 ° C. The temperature was raised to. To this reaction liquid, 14.2 g (0.525 mol) of hydrogen cyanide and 42.6 g (0.525 mol) of 37% formalin
l) and 48% sodium hydroxide aqueous solution 47.1g (0.565mo
l) was added dropwise at 100 ° C. over 1 hour. 100 after dropping
The mixture was stirred at ℃ for 2 hours, and 2% (0.025 mol) of 37% formalin was added to decompose residual hydrogen cyanide. A 50% sulfuric acid aqueous solution was added to adjust the pH to 1.5, and desalting was performed by electrodialysis. The precipitated crystals were collected by filtration. The target product 63 was obtained as a hemihydrate in an amount of 86.1 g (yield 91.3%). In this way, the target group could be promptly introduced even when only the secondary amine was present.

Example 8 Synthesis of Compound 63 Scheme 9

[0107]

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(Synthesis Method of Compound 63) 63.3 g (0.25 mol) of the intermediate 63A, 65.6 g (0.788 mol) of 48% aqueous sodium hydroxide solution and 50.0 g of water were placed in a reaction vessel and stirred at 100 ° C. The temperature was raised to. To this reaction liquid, 6.76 g (0.25 mol) of hydrogen cyanide, 11.0 g (0.25 mol) of acetaldehyde and 20.8 g (0.25 mol) of 48% sodium hydroxide aqueous solution were added.
The mixture was added dropwise at 1 ° C. over 1 hour. After the dropping was completed, the mixture was stirred at 100 ° C for 2 hours, and then hydrogen cyanide (14.2g, 0.525mol) and 37% formalin were added.
42.6 g (0.525 mol) and 48% sodium hydroxide aqueous solution 4
7.1 g (0.565 mol) was added dropwise at 100 ° C over 1 hour. After dropping, stir at 100 ℃ for 2 hours and 2% of 37% formalin
(0.025 mol) was added to decompose residual hydrogen cyanide. A 50% sulfuric acid aqueous solution was added to adjust the pH to 1.5, and desalting was performed by electrodialysis. The precipitated crystals were collected by filtration. 77.7 g (yield 82.4%) of the target product 63 was obtained as a hemihydrate. As described above, even when two kinds of alkylenecarboxylic acids were contained, the final product (target product) could be obtained without isolation and purification on the way. In addition, it was confirmed that the target product was produced in the reaction system even in the case of halogenated alkylcarboxylic acid (brompropionic acid and bromoacetic acid), which was separately performed, but since a large amount of hydrolyzate is mixed, The crystallinity deteriorated, and the yield greatly decreased (yield 41%). From this, it can be said that the manufacturing method of the present invention is excellent.

Example 9 Similarly to the compounds 64, 65, 66 and 67, depending on the reaction conditions using the compound having a cyano group shown in Example 8.
Was synthesized from the intermediates shown in Table 4, and the yields shown in Table 4 were obtained. Table 4

[0110]

[Table 6]

As can be seen from Table 4, the manufacturing method of the present invention is excellent.

Example 10 Of the reaction conditions shown in Example 7, the method was changed to a method in which the raw material formalin and hydrogen cyanide were mixed while being cooled in advance and added dropwise to the liquid in which the amine was present.
As a result, the target compound could be obtained with the same yield as that obtained when the compounds were added separately.

[0113]

According to the method of the present invention, the reaction time can be shortened, and high yield and high purity can be obtained.

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[Procedure amendment]

[Submission date] January 8, 1996

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[Procedure amendment 2]

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[Procedure 3]

[Document name to be amended] Statement

[Correction target item name] 0078

[Correction method] Change

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Hydrogen cyanide or hydrocyanic acid as cyanide
When a salt is used, the compound having a carbonyl (alde
Hydrides (eg formaldehyde, acetaldehyde,
Propionaldehyde), ketones (acetone, methyl)
Ethyl ketone etc.) The molar ratio used here and
It is preferably 1/3 to 3 inclusive. In compound (A),
Compounds having a cyano group (α-hydroxy nitrile compound
To obtain the general formula (I),
-L_Two-CO_TwoM_Two, -L_Three-CO_TwoM_Three, -L _Four-CO_TwoM_FourBoth are different
Carbonyl used in combination with a compound having a nitrile group
Use different compounds each having
It is preferable to carry out the above reactions sequentially. However, this reaction is essential.
No sushi is meant to be isolated. That is, one
When the reaction of is completed, the next reaction may be performed in the same container.
it can. If all three are the same,
The compound having and the compound having carbonyl have one
Use at least 3 times the number of moles required when entering, and
It is preferable to introduce it accordingly. Compound (B) with cyano
Method for obtaining general formula (I) by reacting a compound having a group
The law is -L_Three-CO_TwoM_Three, -L_Four-CO_TwoM_FourBoth are different
Carbonyl used in combination with a compound having a nitrile group
The compounds having
It is preferable to carry out the above reactions sequentially. However, this reaction is essential.
No sushi is meant to be isolated. That is, one
When the reaction of is completed, the next reaction may be performed in the same container.
it can. If both are the same, a compound containing a nitrile group
Compounds with and carbonyl are introduced at one site
Use at least twice the required number of moles and introduce in a single reaction
Is preferred. Hydrogen cyanide used in this reaction
Is the amount of cyanide salt, because it introduces one carboxyl group
To 1 mol of the compound (A) or the compound (B),
0.2 to 15 mol, more preferably 1 to 10 mol, still more preferably
It is preferably 1 to 5 mol. Also has a carbonyl
The amount of compound used is to introduce one carboxyl group
To 1 mole of compound (A) or compound (B).
2 to 15 mol, more preferably 1 to 10 mol, still more preferably
It is preferably 1 to 5 mol. Pair with compounds (A) and (B)
With hydrogen cyanide or cyanide and carbonyl
The carboxy introduced by adjusting the amount ratio of the compound
The number of radicals can be adjusted. Hydrogen cyanide or
Compounds containing hydrocyanic acid salts and carbonyls should be mixed and added.
Or may be added separately at the same time. Ma
Alternatively, they may be added separately at different times. Compound
Where (A) or (B) is present, hydrogen cyanide or
Alternatively, a compound having a hydrocyanic acid salt and a carbonyl may be added.
Yes, and vice versa.

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─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical indication C07C 229/22 C07C 229/22

Claims (3)

[Claims] 1. The following compound (A) or compound (B)
And a hydrogen cyanide, a cyanide, or an α-hydroxynitrile compound are reacted with each other, a method for producing an aminopolycarboxylic acid represented by the following general formula (I). Compound (A) embedded image Compound (B) General formula (I) (In the formula, G ₁ is Or Represents G is Or Represents L ₁ , L ₂ , L ₃ , L ₄ and L ₅ each represent an alkylene group. W ¹ and W ² each represent an alkylene group, an arylene group, an aralkylene group or a divalent nitrogen-containing heterocyclic group. D represents a single bond, -O-, -S- or -N (Rw)-. R _w represents a hydrogen atom, an aliphatic hydrocarbon group, an aryl group or a heterocyclic group. v represents an integer of 0 to 3, and w represents an integer of 1 to 3. Q ₁ and Q
₂ represents a carboxyl group or a cyano group. R _1a is
It represents an aliphatic hydrocarbon group, an aryl group or a heterocyclic group. R _1b represents a hydrogen atom, a hydroxy group or a carboxyl group. Z represents a non-metal atomic group necessary for forming an aryl group or a heterocyclic group. m and n each represent 0 or 1. M ₁ , M ₂ , M ₃ and M
₄ represents a hydrogen atom or a cation. ) 2. The compound (A) or the compound (B)
And hydrogen cyanide are reacted, The manufacturing method of amino polycarboxylic acid represented by General formula (I) of Claim 1. 3. The compound (A) or the compound (B)
And a glycolonitrile are reacted with each other, the method for producing an aminopolycarboxylic acid represented by the general formula (I) according to claim 1.