JP3224282B2 - Aminopolycarboxylic acid derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to the field of metal ion shielding agents, especially medical and cosmetic preparations, soaps, detergents, material analysis, coating on metal materials, plating, catalysts, colloid chemistry, photography, liquid crystals, etc. Novel aminopolycarboxylic acid derivative useful as a metal ion shielding agent in methane.

[0002]

2. Description of the Related Art Conventionally, aminopolycarboxylic acids have been used in medical and cosmetic preparations, soaps, detergents, material analysis, coating on metallic materials, plating, catalysts, colloid chemistry, photography, liquid crystals, antioxidants, separation, Widely used in fields such as analysis. Until now, ethylenediaminetetraacetic acid has been widely used as a chelating agent for the above-mentioned applications. However, development of a chelating agent which is difficult to biodegrade and easily biodegradable from the viewpoint of environmental protection has been desired. The following compounds are conventionally known as similar compounds of the present invention. Compound A

[0003]

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

[0005]

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

[0007]

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(Z. Anorg. Allg. Chem., 397, 187 (1973))
See) the above compounds have low solubility in organic solvents,
It is unsuitable for use in high concentrations in organic solvents. In addition, it was found that compounds B and C were easily decomposed over time in a solution, and were liable to change in performance over a long period of use.

[0009]

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

[0010]

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

[0011]

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(Wherein, R ₁ represents a halogen atom; n represents an integer of 1 to 4. When n is 2 or more, R ₁ represents a halogen atom.
₁ may be the same or different. L ₁ and L ₂
Is an alkylene group having 1 to 10 carbon atoms or a total carbon atom, respectively.
Represents an arylene group represented by Formulas 6 to 14 . M ₁ , M ₂ and M ₃
Represents a hydrogen atom or a cation, respectively. ) General formula (II)

[0013]

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(Wherein, R ₂ represents a group capable of substituting on a naphthalene ring; m represents an integer of 0 to 6; L ₁ and L ₂
Is an alkylene group having 1 to 10 carbon atoms or a total carbon atom, respectively.
Represents an arylene group represented by Formulas 6 to 14 . M ₁ , M ₂ and M ₃
Represents a hydrogen atom or a cation, respectively. However, -CO
OM ₃ is located in an ortho position of _{-N (L 1 COOM 1) (} L 2 COOM 2). )

Hereinafter, the present invention will be described in detail. The alkylene groups represented by L ₁ and L ₂ in the general formulas (I) and (II) may be linear or branched and have 1 to 6 carbon atoms. Examples include a methylene group, an ethylene group, a propylene group, a trimethylene group, and a pentylene group.
The arylene group represented by L ₁ and L _{2 has 6} to ₁ carbon atoms.
0, particularly preferably a phenylene group. Also L
₁ and L ₂ may be different even in the same.

L ₁ and L ₂ may have a substituent. Examples of the substituent which may be present include an alkyl group (eg, a methyl group and an ethyl group), an aralkyl group (eg, a phenylmethyl group), Alkenyl (eg, allyl), alkynyl, alkoxy (eg, methoxy, ethoxy), aryl (eg, phenyl, p
-Methylphenyl group), an amino group (for example, dimethylamino group), an acylamino group (for example, acetylamino group),
Sulfonylamino group (for example, methanesulfonylamino group), ureido group, urethane group, aryloxy group (for example, phenyloxy group), sulfamoyl group (for example, methylsulfamoyl group), carbamoyl group (for example, carbamoyl group, methylcarbamoyl group), Alkylthio group (methylthio group), arylthio group (for example, phenylthio group), sulfonyl group (for example, methanesulfonyl group),
Sulfinyl group (for example, methanesulfinyl group), hydroxy group, halogen atom (for example, chlorine atom, bromine atom,
Fluorine atom), cyano group, sulfo group, phosphono group, aryloxycarbonyl group (for example, phenyloxycarbonyl group), acyl group (for example, acetyl group, benzoyl group), alkoxycarbonyl group (for example, methoxycarbonyl group), acyloxy group (for example, Acetoxy group), carbonamido group, sulfonamido 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 substituent has a carbon atom, it preferably has 1 to 4 carbon atoms. Preferred as L ₁ and L ₂ are those having 1 carbon atom.
And 3 to 3 alkylene groups which may be substituted, and particularly preferred are a methylene group and an ethylene group.

The cations represented by M ₁ , M ₂ and M ₃ in the general formulas (I) and (II) include alkali metals (such as lithium, sodium and potassium), ammonium (such as ammonium and tetraethylammonium), Pyridinium and the like 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 group that can be substituted on the naphthalene ring. Substitutable groups include L ₁
And the substituents which L ₂ may have can be applied. The same applies to the preferred range. m is preferably from 0 to 3, more preferably from 0 to 1, and particularly preferably 0.
Specific examples of the compound represented by formula (I) or (II) are shown below, but the present invention is not limited thereto.

[0018]

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[0019]

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[0020]

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[0021]

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[0022]

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[0023]

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

[0025]

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That is, the compound can be synthesized by reducing the nitro compound (A) to synthesize an amino compound (B), and then reacting the amino compound (B) with a halogen-substituted carboxylic acid derivative.
The method for reducing the nitro compound (A) is not particularly limited, and a method for synthesizing an aniline derivative by reduction of a nitro group can be widely used. For example, “Journal of the Chemical.
Society ”(Journal of the Chemical Society)
371 (1962) can be applied. The reaction between the amino compound (B) and the halogen-substituted carboxylic acid derivative can be performed, for example, by the method described in “Journal of the American Chemical Society”.
Chemical Society) 80, 800 (1958) and the like. This reaction is usually performed in a solvent.
The solvent is not limited as long as it does not participate in the reaction,
The use of water, alcohol (methanol, ethanol, isopropanol, etc.) advantageously proceeds. The reaction is preferably performed in the presence of a base, and examples of the base include alkalis (such as sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate) and tertiary amines (such as triethylamine). When X ₁ and X ₂ in the halogen-substituted carboxylic acid derivative are a chlorine atom or a bromine atom, an iodide ion is added (preferably in a molar amount of 0.01 to 2 times the amine compound (B) as a raw material). This is preferable because the reaction proceeds promptly. In addition, when L ₁ and L ₂ are ethylene in the general formula (I) or (II), acrylic acid may be used in the synthesis instead of the halogen-substituted alkyl carboxylic acid. EXAMPLES Next, the present invention will be described in detail with reference to Examples, 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 ml 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 dropped so that the pH was maintained at 7 to 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 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 an aqueous solution of 4.0 g (0.10 mol) of sodium hydroxide / 5 ml of water was added dropwise with stirring at room temperature. The mixture was heated to 100 ° C., and a solution of 39.3 g (0.32 mol) of sodium chloroacetate / 30 ml of water and 13.2 g (0.33 mol) of sodium hydroxide /
A 15 ml solution of water was slowly added dropwise to keep the pH at 7 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 and recrystallized from water to give 13.2 g (0.03 g) of the desired product.
41 mol). 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 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 an aqueous solution of 4.0 g (0.10 mol) of sodium hydroxide / 5 ml of water was added dropwise with stirring at room temperature. Heat to 100 ° C. and add sodium chloroacetate
A solution of 3 g (0.32 mol) in 30 ml of water and a solution of 13.2 g (0.33 mol) of sodium hydroxide in 15 ml of water are mixed with p.
It was slowly dropped to keep H7-10. 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 further recrystallized from acetonitrile to obtain 8.70 g (0.029 mol) of the desired product. 29% yield

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) Each of the comparative compound and the compound of the present invention was 0.1%.
01 mol was added to 100 ml of methanol, and the solubility at 30 ° C. was compared. Table 1 shows the results.

[0033]

[Table 1]

[0034]

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As is clear from Table 1, the comparative compound is not completely dissolved, whereas the compounds of the present invention are completely dissolved and have high solubility in methanol as an organic solvent.

(Aging stability test) Comparative compounds B, C and
The compound of the present invention was prepared using 1M Na_TwoCO_Three/ 1M NaHCO
_ThreeDissolve in a buffer solution adjusted to pH 11 with an aqueous solution,
/ H_TwoO = 1/1 (vol / vol) 1 mmol solution was prepared
Was. 100 ml of this solution has an opening area of 45 cm^TwoBeaker
After stirring at 40 ° C. for 2 weeks, the compound remains
The amount was determined by high performance liquid chromatography. still,
For water evaporation, add water to make the solution 100ml
I did it. Table 2 shows the results.

[0037]

[Table 2]

As is clear from Table 2, the compounds of the present invention are superior in stability over time as compared with Comparative Compounds B and C.

(Biodegradability test) The ethylenediaminetetraacetic acid and the compounds I-1, I-2 and II-1 of the present invention were subjected to a biodegradability test according to the SCAS method defined in the OECD guidelines. While ethylenediaminetetraacetic acid did not biodegrade, the compound of the present invention was found to be biodegradable and readily biodegradable.

[0040]

The aminopolycarboxylic acid derivative of the present invention can be used as a metal ion shielding agent, for example, in medical or cosmetic preparations.
Suitable for soap, detergent, material analysis, coating on metal materials, plating, catalyst, colloid chemistry, photography, liquid crystal, antioxidants, separation, analysis, etc., solubility in organic solvents, stability over time in liquid Excellent in biodegradability.

Continuation of the front page (58) Fields investigated (Int. Cl. ⁷ , DB name) C07C 229/40-229/44 C07C 229/52-229/74 C09K 3/00 108 CAPLUS (STN) REGISTRY (STN)

Claims (2)

(57) [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 is total
Represents an alkylene group having 1 to 10 carbon atoms or an arylene group having 6 to 14 carbon atoms in total . M ₁ , M ₂ and M ₃ each represent 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 that can be substituted on a naphthalene ring.
Represents an integer of 0 to 6. L ₁ and _{L 2,} respectively Total
Represents an alkylene group having 1 to 10 carbon atoms or an arylene group having 6 to 14 carbon atoms in total . M ₁ , M ₂ and M ₃ each represent a hydrogen atom or a cation. However, -COOM ₃ is -N
(L ₁ COOM ₁ ) is located at the ortho position of (L ₂ COOM ₂ ). )