JPH06107612A - Aminopolycarboxylic acid derivative - Google Patents

Abstract

PURPOSE:To obtain a new biodegradable aminopolycarboxylic acid derivative, useful as a metallic ion shielding agent in the field of medical and cosmetic formulations, soaps, detergents, material analysis, platings, catalysts, liquid crystals, etc., and excellent in solubility in organic solvents and stability with time. CONSTITUTION:The objective aminopolycarboxylic acid derivative of formula I [R1 is halogen; (n) is 1-4; L1 and L2 are alkylene or arylene; M1 to M3 are H or cation] or formula II [R2 is group substitutive in naphthalene ring; (m) is 0-6, with the proviso that COOM3 is located at the o-position with respect to N(L1COOM1) (L2COOM2)], e.g. compounds of formulas III and formula IV. This compound of formula I or II is obtained by reducing, e.g. a nitro derivative of formula V, providing an amino derivative of formula VI and then reacting the resultant amino derivative with halogen-substituted carboxylic acid derivatives of formula VII (X1 and X2 are halogen).

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to the field of metal ion shielding agents, especially for medical and cosmetic preparations, soaps, detergents, material analysis, coating on metal materials, plating, catalysts, colloid chemistry, photography, liquid crystals, etc. The present invention relates to a novel aminopolycarboxylic acid derivative useful as a metal ion shielding agent.

[0002]

2. Description of the Related Art Conventionally, aminopolycarboxylic acids have been used for medical and cosmetic preparations, soaps, detergents, material analysis, coating on metal materials, plating, catalysts, colloid chemistry, photography, liquid crystals, antioxidants, separation, Widely used in fields such as analysis. Up to now, ethylenediaminetetraacetic acid has been often used as a chelating agent for the above-mentioned applications, but it has been desired to develop a chelating agent which is not easily biodegradable and is easily biodegradable from the viewpoint of environmental protection. The following compounds are conventionally known as similar compounds of the present invention. Compound A

[0003]

[Chemical 3]

(See J. Am. Chem. Soc., 80, 800 (1958), etc.) Compound B

[0005]

[Chemical 4]

(See J. Inorg. Nucl. Chem., 29, 1164 (1967)) Compound C

[0007]

[Chemical 5]

(Z. Anorg. Allg. Chem., 397, 187 (1973)
The above compound has low solubility in an organic solvent,
It is unsuitable for use in high concentrations in organic solvents. Further, it was found that the compounds B and C were easily decomposed with time in the solution, and the performance was apt to change during long-term use.

[0009]

DISCLOSURE OF THE INVENTION The present invention provides a novel aminopolycarboxylic acid derivative which is useful as a metal ion shielding agent, has excellent solubility in organic solvents and stability over time, and is biodegradable. .

[0010]

The aminopolycarboxylic acid derivative of the present invention is represented by the following general formula (I) or (II). General formula (I)

[0011]

[Chemical 6]

(In the formula, R ₁ represents a halogen atom. N represents an integer of 1 to 4. When n is 2 or more, R 1
₁ may be the same or different. L ₁ and L ₂
Each represents an alkylene group or an arylene group.
M ₁ , M ₂ and M ₃ each represent a hydrogen atom or a cation. ) General formula (II)

[0013]

[Chemical 7]

(In the formula, R ₂ represents a group capable of substituting on the naphthalene ring. M represents an integer of 0 to 6. L ₁ and L ₂
Each represents an alkylene group or an arylene group.
M ₁ , M ₂ and M ₃ each represent a hydrogen atom or a cation. However, -COOM ₃ is -N (L ₁ COOM ₁₎
It is located in the ortho position of (L ₂ COOM ₂ ). )

The present invention will be described in detail below. The alkylene groups represented by L ₁ and L ₂ in the general formulas (I) and (II) may be linear or branched, and preferably have 1 to 6 carbon atoms. Examples thereof include methylene group, ethylene group, propylene group, trimethylene group, and pentylene group. The arylene group represented by L ₁ and L ₂ preferably has 6 to 10 carbon atoms, and a phenylene group is particularly preferable. L ₁ and L ₂ may be the same or different.

L ₁ and L ₂ may have a substituent, and examples of the substituent which may have include an alkyl group (eg, methyl group, ethyl group), an aralkyl group (eg, phenylmethyl group), Alkenyl group (eg allyl group), alkynyl group, alkoxy group (eg methoxy group, ethoxy group), aryl group (eg phenyl group, p
-Methylphenyl group), an amino group (for example, dimethylamino group), an acylamino group (for example, acetylamino group),
Sulfonylamino group (eg methanesulfonylamino group), ureido group, urethane group, aryloxy group (eg phenyloxy group), sulfamoyl group (eg methylsulfamoyl group), carbamoyl group (eg carbamoyl group, methylcarbamoyl group), Alkylthio group (methylthio group), arylthio group (eg phenylthio group), sulfonyl group (eg methanesulfonyl group),
Sulfinyl group (eg methanesulfinyl group), hydroxy group, halogen atom (eg chlorine atom, bromine atom,
Fluorine atom), cyano group, sulfo group, phosphono group, aryloxycarbonyl group (eg phenyloxycarbonyl group), acyl group (eg acetyl group, benzoyl group), alkoxycarbonyl group (eg methoxycarbonyl group), acyloxy group (eg (Acetoxy group), carbonamide group, sulfonamide group, nitro group, hydroxamic acid group and the like. Preferred substituents are a hydroxy group, a carboxyalkyl group, a carboxyalkoxy group, a halogen atom and an aryl group. When the above substituent has a carbon atom, it preferably has 1 to 4 carbon atoms. L ₁ and L ₂ preferably have 1 carbon atom.
To 3 optionally substituted alkylene groups, particularly preferably a methylene group or an ethylene group.

The cations represented by M ₁ , M ₂ and M ₃ in the general formulas (I) and (II) include alkali metals (lithium, sodium, potassium, etc.), ammonium (ammonium, tetraethylammonium, etc.), Pyridinium etc. can be mentioned. Examples of the halogen atom represented by R ₁ in the general formula (I) include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. n is preferably 1 or 2, and more preferably 1.
In the general formula (II), the substituent of R _{2 represents} a substitutable group on the naphthalene ring. The substitutable group is L ₁
And those mentioned as the substituents which L ₂ may have are applicable. The preferable range is also the same. m is preferably 0 to 3, more preferably 0 to 1, and particularly preferably 0.
Specific examples of the compounds represented by formula (I) or (II) are shown below, but the invention is not limited thereto.

[0018]

[Chemical 8]

[0019]

[Chemical 9]

[0020]

[Chemical 10]

[0021]

[Chemical 11]

[0022]

[Chemical 12]

[0023]

[Chemical 13]

The compound represented by the above general formula (I) can be synthesized, for example, by the method represented by the following formula (1).

[0025]

[Chemical 14]

That is, it can be synthesized by reducing the nitro compound (A) to synthesize the amino compound (B) and then reacting the amino compound (B) with the halogen-substituted carboxylic acid derivative.
The method for reducing the nitro compound (A) is not particularly limited, and a synthetic method of an aniline derivative by reducing a nitro group can be widely used. For example, “Journal of the Chemical
Society "(Journal of the Chemical Society)
The method described in 371 (1962) can be applied. The reaction between the amino compound (B) and the halogen-substituted carboxylic acid derivative is described in, for example, “Journal of the American Chemical Society” (Journal of the American C
Chemical Society) 80, 800 (1958) and the like can be referred to. This reaction is usually performed in a solvent.
The solvent is not limited as long as it does not participate in the reaction,
Use of water, alcohol (methanol, ethanol, isopropanol, etc.) or the like will proceed advantageously. The 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). When X ₁ and X ₂ in the halogen-substituted carboxylic acid derivative are chlorine atom or bromine atom, iodide ion is added (preferably 0.01 to 2 times mol based on the starting amine compound (B)). ) Is preferable because the reaction proceeds rapidly. In the general formula (I) or (II), when L ₁ and L ₂ are ethylene, acrylic acid can be used instead of the halogen-substituted alkylcarboxylic acid for the synthesis. Next, examples will be given to specifically describe the present invention, but the present invention is not limited thereto.

[0027]

【Example】

(Synthesis Method of Compound I-1) 17.2 g (0.10 mol) of 2-amino-4-chlorobenzoic acid, 39.3 g (0.32 mol) of sodium chloroacetate, and 50 ml of water were placed in a three-necked flask, and 85 Heat to ~ 90 ° C and, with stirring, 14.2 g (0.33 mol) of sodium hydroxide / 15 ml of water
The aqueous solution was slowly added dropwise so that the pH was maintained at 7-9.
After heating and stirring for 4 hours, the temperature was returned to room temperature, and 50 ml of water and 50 ml of concentrated hydrochloric acid were added dropwise. The precipitated solid was collected by filtration and recrystallized from water to give 17.8 g (0.062 mol) of the desired product.
l) Got it.

Yield 62% Melting point 189-191 ° C (decomposition) ¹ HNMR (D ₂ O + NaOD) δppm δ 4.14 (s 4H) δ 7.45 (dd 1H) δ 7.66 (d 1H) δ 7.98 (d 1H)

(Synthesis Method of Compound I-2) 2-Amino-
20.6 g (0.10 mol) of 3,5-dichlorobenzoic acid and 30 ml of water were placed in a three-necked flask, and 4.0 g (0.10 mol) of sodium hydroxide / 5 ml of water aqueous solution was added dropwise while stirring at room temperature. Heated to 100 ° C., sodium chloroacetate 39.3 g (0.32 mol) / water 30 ml solution and sodium hydroxide 13.2 g (0.33 mol) /
A 15 ml solution of water was slowly added dropwise so as to keep the pH at 7-10. After heating and stirring for 4 hours, the temperature was returned to room temperature, and 86 ml of water and 37 ml of concentrated hydrochloric acid were added dropwise. The precipitated solid was collected by filtration and recrystallized from water to obtain 13.2 g (0.0
41 mol) was obtained. Yield 41%

Melting point 193-195 ° C. (decomposition) ¹ HNMR (D ₂ O + NaOD) δppm δ 4.10 (s 4H) δ 7.64 (d 1H) δ 7.71 (d 1H)

(Synthesis Method of Compound II-1) 2-Amino-2
-23.4 g (0.10 mol) of naphthoic acid and 60 ml of water were placed in a three-necked flask, and 4.0 g (0.10 mol) of sodium hydroxide / 5 ml of water aqueous solution was added dropwise while stirring at room temperature. Heat to 100 ° C. and sodium chloroacetate 39.
A solution of 3 g (0.32 mol) in 30 ml of water and a solution of 13.2 g of sodium hydroxide (0.33 mol) in 15 ml of water was added.
The solution was slowly added dropwise so as to keep H7 to 10. After heating and stirring for 4 hours, the temperature was returned to room temperature, and 86 ml of water and 37 ml of concentrated hydrochloric acid were added dropwise. The precipitated solid was collected by filtration, recrystallized from water, and then recrystallized from acetonitrile to obtain 8.70 g (0.029 mol) of the desired product. Yield 29%

Melting point 214-215 ° C. (decomposition) ¹ HNMR (D ₂ O + NaOD) δppm δ 3.86 (s 4H) δ 7.18 (s 1H) δ 7.40 (ddd 1H) δ 7.50 (ddd 1H) δ 7.79 (dd 1H) δ 7.84 (dd 1H) δ 7.91 (s 1H) (Solubility test) Comparative compound and the compound of the present invention were each 0.
01 mol was added to 100 ml of methanol, and the solubility at 30 ° C. was compared. The results are shown in Table 1.

[0033]

[Table 1]

[0034]

[Chemical 15]

As is clear from Table 1, the comparative compounds are not completely dissolved, whereas all the compounds of the present invention are completely dissolved and are highly soluble in the organic solvent methanol.

(Stability test with time) Comparative compounds B, C and
The compound of the present invention was treated with 1M Na₂CO₃/ 1M NaHCO
₃Dissolve in a buffer solution adjusted to pH 11 with an aqueous solution,
/ H₂Prepare a solution of O = 1/1 (vol / vol) 1 mmol
It was 100 ml of this solution has an opening area of 45 cm²Beaker
After 40 hours at 40 ° C with stirring, the compound remains
The amount was quantified by high performance liquid chromatography. still,
For water evaporation, add water to make the solution 100 ml
I did it. The results are shown in Table 2.

[0037]

[Table 2]

As is clear from Table 2, the compounds of the present invention are superior in stability over time to the comparative compounds B and C.

(Biodegradability test) When ethylenediaminetetraacetic acid and the compounds I-1, I-2 and II-1 of the present invention were subjected to a biodegradability test in accordance with the SCAS method defined in the OECD guideline, It was found that ethylenediaminetetraacetic acid did not biodegrade, whereas the compound of the present invention showed biodegradability and was easily biodegradable.

[0040]

The aminopolycarboxylic acid derivative of the present invention is used as a metal ion shielding agent, for example, for medical or cosmetic preparations,
Suitable for use in soaps, detergents, material analysis, coating on metallic materials, plating, catalysts, colloid chemistry, photography, liquid crystals, antioxidants, separation, analysis, etc., solubility in organic solvents, stability over time in liquid , Excellent in biodegradability.

─────────────────────────────────────────────────── ───

[Procedure amendment]

[Submission date] December 4, 1992

[Procedure Amendment 1]

[Document name to be amended] Statement

[Name of item to be corrected] Claim 2

[Correction method] Change

[Correction content]

[Chemical 2] (In the formula, R ₂ represents a group capable of substituting on the naphthalene ring. M
Represents an integer of 0 to 6. L ₁ and L ₂ each represent an alkylene group or an arylene group. M ₁ , M ₂ and M
Each ₃ represents a hydrogen atom or a cation. However, -C
OOM ₃ is -N (L ₁ COOM ₁ ) (L ₂ COOM ₂ ).
Located in the ortho position. )

[Procedure Amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0013

[Correction method] Change

[Correction content]

[0013]

[Chemical 7]

[Procedure 3]

[Document name to be amended] Statement

[Name of item to be corrected] 0024

[Correction method] Change

[Correction content]

The compound represented by the above general formula (I) or (II) can be synthesized, for example, by the method represented by the following formula (1).

[Procedure amendment 4]

[Document name to be amended] Statement

[Name of item to be corrected] 0025

[Correction method] Change

[Correction content]

[0025]

[Chemical 14]

Claims (2)

[Claims] 1. An aminopolycarboxylic acid derivative represented by the following general formula (I). General formula (I) (In the formula, R ₁ represents a halogen atom. N represents an integer of 1 to 4. When n is 2 or more, R ₁ may be the same or different. L ₁ and L ₂ each represents an alkylene group or an arylene group, M ₁ , M ₂ and M
Each ₃ represents a hydrogen atom or a cation. ) 2. An aminopolycarboxylic acid derivative represented by the following general formula (II). General formula (II) (In the formula, R ₂ represents a group capable of substituting on the naphthalene ring. M
Represents an integer of 0 to 6. L ₁ and L ₂ each represent an alkylene group or an arylene group. M ₁ , M ₂ and M
Each ₃ represents a hydrogen atom or a cation. However, -C
OOM ₃ is -N (L ₁ COOM ₁ ) (L ₂ COOM ₂ ).
Located in the ortho position. )