WO2003020689A1

WO2003020689A1 - Chelating agents and their metal chelates

Info

Publication number: WO2003020689A1
Application number: PCT/EP2002/009353
Authority: WO
Inventors: Arnold Johan Kleijer; Martin Heus; Adrianus Maria Reichwein
Original assignee: Akzo Nobel N.V.
Priority date: 2001-08-30
Filing date: 2002-08-20
Publication date: 2003-03-13

Abstract

The invention pertains to a chelating agent of the formula: (I) wherein Z is cyclohexylene or (CR2)n wherein R is independently H or C1-4 alkyl, and n is an integer of 2-4; X is (CR'2)mCOO-M+ wherein R' is independently H or CH¿3,? m is an integer of 0-3, and M is selected from H, Na, K, and NH4; and Y is independently selected from H, oh, COOOH, SO3H, PO3H2, C1-4 alkyl, halogen, CN, and NO2. The invention further pertains to this chelating agent and a metal ion, preferably manganese ion, preferably to combat manganese ion deficiency in plant cultivation.

Description

CHELATING AGENTS AND THEIR METAL CHELATES

The present invention pertains to chelating agents, metal chelates thereof, and to their use for the treatment of metal ion deficiency in plant cultivation.

Manganese deficiency is a common problem in agriculture, in field crops as well as in fruit orchards, gardening, and other forms of plant cultivation. As a remedy some soils may be treated with manganese salts, usually the sulfate, but the manganese soon forms insoluble oxides, which are no longer available to the plants. "Banded" application is therefore recommended, whereas general or broadcast application is ineffective. Instead, in most cases manganese deficiency is treated or prevented by foliar application of manganese sulfate.

In the case of other micro-elements, e.g. iron, deficiencies are often more conveniently treated by general soil application such as broadcasting or drip irrigation. The metal is kept soluble in the form of a suitable chelate. It has long been a desire to find a manganese chelate of such utility. Attempts to use ordinary manganese (Mn ⁺) chelates of known chelating agents such as EDTA and DTPA have proved counterproductive, the problem being that the chelating agent is taken over by iron and/or calcium from the soil and the manganese set free is soon oxidized to insoluble oxides.

Iron tends to be abundant in soils. Because of its trivalent positive charge, feme ions are known to form very stable chelates with most chelating agents, e.g., EDTA or DTPA. For manganese, a normal state is the divalent manganese (II) cation, which forms chelates of much lower stability than iron. Consequently, it is well known that manganese (II) chelates when applied to soil are rapidly decomposed, and rendered useless, by the iron in the soil.

There are known to be chelates of trivalent manganese of the same order of stability as iron. The phenolic chelating agents, e.g. EDDHA (EHPG), long used in the form of their ferric chelates on alkaline soils, would be candidates to form manganese (III) chelates of fair hydrolytic stability. However, the inventors have found that in the presence of an iron- containing soil these manganese (III) chelates decompose too rapidly. This is in accordance with the findings reported by Ahrland, Dahlgren and Persson (Acta Agric. Scand, 4:101-111, 1990). These authors report that manganese (III) chelates generally are more prone to hydrolysis than ferric chelates. For manganese (III) EDDHA (EHPG) a pKa value of 9.3 is reported for hydrolysis, whereas results according to the present invention indicate a corresponding pKa for the new ligands of at least 11.

For iron, the situation is the reverse. A pKa value for hydrolysis of 12.7 is reported by the same authors, whereas the ligand according to the present invention has a pKa for iron of about 9-10.

A manganese (III) chelate with a stability of approximately the same order as that of the ferric chelate allows a considerable proportion of manganese (III) ions to be set free in the soil. Accordingly the invention pertains to a novel chelating agent having a high selectivity to manganese (III) ion over ferric ion. Very high stability of the manganese (III) chelate is desirable, since the formation of insoluble manganese oxides will be accelerated by a so- called dismutation of two manganese (III) ions to form one manganese (II) ion and one mole of manganese dioxide. The oxidation of soil manganese to the dioxide is also promoted by certain soil bacteria.

It is an object of the present invention to provide a metal ion chelate, and more preferably a manganese chelate with a high stability in comparison to iron and other metal ions present in soil and a high resistance to decomposition by hydrolysis, and more particularly, to provide a manganese chelate which remains in the soil for an effective period and can therefore be used for this treatment of manganese deficiency by general application to the soil and other growing substrates.

The chelating agents according to the present invention are of the general formula,

wherein

Z is cyclohexylene or (CR₂)_n wherein R is independently H or C1-4 alkyl, and n is an integer of 2-4;

X is (CR'₂)_mCOO^"M⁺ wherein R' is independently H or CH₃, m is an integer of 0-3 and M is selected from H, Na, K, and NH₄; and

Y is independently selected from H, OH, COOH, SO₃H, PO₃H₂, C1-4 alkyl, halogen, CN, and NO₂.

The term "cyclohexylene" means 1 ,2-, 1 ,3-, or 1 ,4-cyclohexylene. Halogen means chlorine, bromine, or iodine, and C1-4 alkyl is an alkyl group with 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, sec.butyl, and tert.butyl.

The inventors have surprisingly found that the chelating agents according to the present invention are highly selective to manganese (III) ions in the presence of iron and that the manganese (III) chelates also exhibit a remarkable resistance to hydrolysis and show a good ability to remain soluble in the presence of an iron-containing soil. Although the invention for the above given reasons is pre-eminently suitable for chelation of manganese (III) ions, the chelating agents are also suitable for chelating other ions such as copper, iron, zinc, cobalt, and nickel ions. For these ions the stability towards iron plays a lesser role, or no role at all. However, it was found that the presently claimed chelating agents which are not chelated with the metal ion, decompose into small entities, each of which is excellently biodegradable. This is not the case for chelating agents according to the prior art. For this reason it is beneficial to use these chelating agents also for other ions than manganese (III) ions only.

Not wishing to be bound by any theory, the inventors believe the selectivity of the chelating agents according to the present invention to be found in a rigid salen structure

(abbreviation for salicylaldehyde-ethylenediamineadduct).

In the preferred manganese (III) chelates of the chelating agents according to the present invention, the rigid, equatorial structure is thought to be formed by the phenol and imine groups in the salen structure, which is known to prefer a stable, planar structure in its metal chelates.

The resonance structure of the phenol and imine groups is believed to exchange metal ions very slowly after a complex has been formed. When the present molecule is applied to the soil as a manganese (III) chelate, the exchange with the iron present in the soil is negligible. Alkaline, neutral, or weakly acidic soils are usually more or less aerated. When manganese is applied to such a soil, it will slowly, but inevitably be oxidized to insoluble manganese dioxide. However, if the manganese is very strongly chelated, it can, in principle, be kept soluble and available to the plants for a sufficient time, e.g., weeks or months.

To uphold such strong chelation of manganese ions requires a high resistance of the chelate to hydrolysis, especially at high soil pH.

The manganese (III) chelates according to the present invention form stable aqueous solutions up to a pH of 10.5 - 11 , indicating a pKa for hydrolysis of at least about 11. The ferric chelates of the same chelating agents exhibit stability up to a pH of about 9-10.

Another characteristic of the present invention is a high stability compared to other metal ions that may compete for the chelating agent and thereby set free manganese ions.

For comparison, the corresponding chelating agent with secondary amino functions instead of the imine groups is known as the above mentioned EDDHA (EHPG) and shows no selectivity to a manganese (III) ion. The selectivity is also significantly improved when compared with the chelating agent as disclosed in WO 99/02487.

In addition to the salen structure, other four-dentate chelating units containing two imine nitrogens and two hydroxy anions can enclose the manganese (III) ion in a similar way and form the basis of chelating agents with a corresponding selectivity to manganese (III) ion.

The chelating agent is preferably a salt, i.e. M is selected from Na, K and NH₄. The advantage of salts over the free acid (i.e. M is H) is the improved solubility in aqueous systems.

In case Z is (CR₂)_n in the chelating agent of the present invention, n is preferably 2.

Preferred chelating agents are those of the aforementioned formula wherein m is 2, or preferably 0.

It is also preferred that both aromatic OH groups are in the ortho position. Of the substituents Y, the preferred are H, OH, COOH, SO₃H, or C1-4 alkyl, of which H and CH₃ are the most preferred.

The preferred group X is COONT, which leads to chelating agents with good solubility properties. M is selected from H, Na, K, and NH , preferably from Na, K, and NH .

The following chelating agent having the formula:

wherein both groups Y are H or CH₃, are particularly preferred compounds, and wherein M is H or preferably Na, K, and NH₄.

According to a further aspect of the present invention, a chelate comprising the above referenced chelating agent is provided, with a di- or trivalent metal ion attached to it. The metal ion in the chelate preferably has a 3⁺ oxidation state and is most preferably manganese.

If the negative charge of the chelating agent exceeds the positive charge of the metal ion, the chelate can comprise further metal cations to compensate the excess negative charge of the chelate. The chelate preferably is water-soluble.

Another aspect of the present invention deals with the use of this chelating agent and/or chelate to combat metal ion deficiency, preferably to combat manganese ion deficiency, in plant cultivation.

According to a further aspect of the present invention a process is provided for providing the above chelating agent, which process comprises the step of reacting preferably approximately 2 molar equivalents of a relevant hydroxy-oxo compound, or a suitable derivative thereof, with preferably approximately 1 molar equivalent of a relevant diamino compound, preferably 1,2-ethylenediamine (EDA). The hydroxy-oxo compound preferably is 2-hydroxy-α-oxo-phenyl acetic acid: The hydroxy-oxo compound can be provided by the hydroxy-alkylation of phenol via a condensation reaction with a suitable oxo compound, preferably glyoxylic acid, followed by oxidation.

The manganese (III) chelates according to the present invention can be produced using a trivalent manganese (III) salt such as the acetate, Mn(OAc)₃.

Alternatively, the chelate according to the present invention can be yielded, for example, by reacting the appropriate chelating agent with a divalent metal ion, preferably a salt of divalent manganese, such as manganese (II) sulfate, and subsequently oxidizing to the trivalent state, for example with air or another oxidant, such as permanganate or manganese dioxide.

The invention will now be further described by way of the following Examples:

Experimental background:

Introduction

The di-imine chelating agents of the invention were prepared by the condensation of one mole of an appropriate diamino compound with two moles of a suitable hydroxy-oxo compound as defined in process 1 or 2 below, or a suitable derivative thereof. To prepare the chelating agent of the present invention two processes, i.e. process 1 and process 2, were examined by the inventors:

Process 1

The first reaction scheme used indole-2,3-dione (isatin) as starting material and produced material with a very high purity.

T= heating

Process 2

The second reaction scheme used phenol and glyoxylic acid as starting materials.

Example 1

Synthesis of the chelating agent according to the present invention via process 1 The chelating agent was synthesized from indole-2,3-dione (isatin) and ethylenediamine. The product was subsequently tested for manganese selectivity over iron.

Synthesis of 2.3-coumarandione (reaction step 1 )

50 g (0.34 mole) of indole-2,3-dione were dissolved in 200 ml 2M sodium hydroxide solution, and the resulting solution was cooled to 5°C. 23.5 g (0.34 mole) of sodium nitrite were then quickly added. In 4 hours, 500 ml of 2M sulfuric acid were added dropwise, while keeping the temperature below 5°C. After stirring for another hour at 5°C the temperature was raised carefully to 80°C and maintained for 6 hours. The cooled reaction mixture was extracted 3 times with 100 ml of diethyl ether. The combined organic layers were dried over magnesium sulfate and evaporated to dryness, leaving 40 g of a black tar. Vacuum distillation (120°C/1mmHg) yielded 20 g (0.14 mole) of 2,3-coumaranedione as a crystalline yellow solid. The structure was confirmed by ¹H and ¹³C NMR.

Synthesis of N.N'-ethylene diamine bis(α-carboxy-salicylidene) (step 2) 2.96 g (0.02 mole) of 2,3-coumarandione from step 1 and 0.80 g (0.02 mole) of sodium hydroxide were dissolved in 50 ml of water. In 5 minutes, 0.60 g (0.01 mole) of ethylene diamine was added. Approximately 10 ml of ethanol were added to complete dissolution.

After stirring for 16 hours at room temperature the mixture was evaporated leaving a yellow solid. 0.33 g of the yellow solid was dissolved in the smallest amount of water possible and acidified with 4M hydrochloric acid. A white precipitate was filtered off and dried, resulting in 150 mg (30% yield) of N.N'-ethylene diamine bis (α-carboxy-salicylidene).

Example 2 Investigating the chelating properties of N.N'-ethylene diamine bis(α-carboxy-salicylidene)

Chelating agent solution

333.8 mg (0.94 mmole) of N.N'-ethylene diamine bis(α-carboxy-salicylidene)from reaction step 2 were dissolved in 50 ml of water. The pH was adjusted to 8.5 using 1M sodium hydroxide solution. The solution was diluted to 100 ml to obtain a concentration of 0.0094 mmole of chelating agent per ml.

Preparing a manganese (III) chelate of the chelating agent

5 ml of the obtained chelating agent solution (max 0.047 mmole) were diluted with 20 ml of water. 5 ml of a solution containing 0.007 mmole of manganese (II) sulfate and 1 eq. of sodium citrate per ml were added. Finally, 5 ml of a solution containing 0.002 mmole potassium permanganate per ml were added dropwise in order to transform all manganese to the trivalent stage (eventually 0.045 mmole manganese). A brown ochre color formed in the course of a few minutes. The pH was adjusted to 8.0 using dilute sodium hydroxide and the volume was adjustable to 100 ml.

Example 3

Investigating the hydrolytic stability of the manganese (III) chelate

The manganese (III) chelate solution from Example 2 was prepared several times, each solution having a different final pH.

The flasks were inspected at regular time intervals.

The results are shown in the following Table 1.

Table 1

Example 4

Formation and investigation of the hydrolytic stability of a ferric chelate of the chelating agents according to the present invention 5 ml of the chelating agent solution from Example 2 (0.047 mmole) were diluted with 20 ml of water. 5 ml of a solution containing 0.009 mmole of ferric nitrate and 1 eq. of sodium citrate per ml were subsequently added. The pH of the solution was adjusted to 7.0 and diluted to 100 ml, yielding a slightly red solution. Four ferric chelate solutions having different pH values were prepared. The flasks were examined at several time intervals. The results are shown in Table 2. The formation of iron chelate resulted in a reddish/pink color.

Table 2

Examples 3 and 4 show that the ferric chelate of the new chelating agent has a lower hydrolytic stability than the manganese (III) chelate, since precipitation occurred at a pH of 11 after only 2 days, whereas for the manganese (III) chelate of Example 3, precipitation was observed at this pH after 2 weeks.

Example 5

Stability of the manganese (III) chelate in the presence of iron ions In order to investigate the preference of the chelating agent according to the present invention for manganese (III) ions over ferric ions, stable solutions of these ions were prepared. Citric acid was added in order to prevent the formation of metal hydroxide at elevated pH. The solutions were set to a pH of 8 and diluted to 100 ml. In the table below, "(A)" stands for a solution comprising manganese (III) ions and the chelating agent "L". "(B)" stands for a solution which is identical to solution (A) except that ferric ions were used instead of manganese (III) ions. "(C)" stands for a solution which is identical to solution (A), except that it additionally contained ferric ions in an amount equimolarto the amount of manganese (III) ions. Table 3

Both (A) and (C) formed a brown/ochre color typical of the manganese (III) chelate as reported in Example 2, whereas (B) formed a slightly pink color. The ochre color of (A) and (C) was stable for weeks, apparently indefinitely so. Consequently, the selectivity of the chelating agent of the invention to manganese (III) ions is significantly higher than to ferric ions.

Example 6

Synthesis of the manganese selective chelate. according to process 2

The chelating agent was synthesized from phenol, glyoxylic acid, and ethylene diamine.

Step l

The reaction of phenol with glyoxylic acid (step 1) yielded a large fraction of 2-hydroxy-α- hydroxyphenyl acetic acid when a small amount of Al³⁺ (sulfate) was added to the reaction mixture. To isolate the pure ortho product, the potassium salt of 2-hydroxy-α- hydroxyphenyl acetic acid was extracted from the evaporated reaction mixture with acetone.

Step 2

The 2-hydroxy-α-hydroxyphenyl acetic acid was then oxidized by O₂, and a mixture of Pt on carbon and Pb²⁺ (nitrate). Using evaporation, acidification, filtration and extraction steps, the 2-hydroxy-α-oxophenyl acetic acid was isolated.

Condensation of phenol and glyoxylic acid (step 1)

643 g (6.8 mole) of phenol, 92 g (1.0 mole) of glyoxylic acid monohydrate, and 2.41 g (0.01 mole) of aluminum chloride hexahydrate were dissolved in 700 ml of water. 58 g (1.0 mole) of potassium hydroxide were slowly added. The pH had a value of 4.8 after the addition. The reaction mixture was slowly heated and kept at reflux temperature for 6 hours. After cooling to room temperature, phenol was removed by extraction with 3 x 350 ml diethyl ether. The water layer was evaporated, leaving 189 g of a slightly yellow solid. The solid was stirred with 800 ml of acetone for several hours and filtered. The acetone was evaporated to dryness, resulting in 91 g (0.49 mole, 49% yield) of 2-hydroxy-α- hydroxyphenyl acetic acid as an off-white foam. The structure was confirmed by ¹H and ¹³C NMR.

Oxidation of 2-hydroxy-α-hvdroxyphenyl acetic acid (step 2) 15.5 g (0.08 mole) of 2-hydroxy-α-hydroxyphenyl acetic acid, and 10 g (0.08 mole) of a 45% potassium hydroxide solution were dissolved in 200 ml of water. 1.5 g 1% Pt/C were added and 0.5 g (1.5 mmole) of lead nitrate was added as a solution in 10 ml of water. The solution was heated to 80°C and air was replaced by pure oxygen. The reaction mixture was stirred under pure oxygen for 6 hours until the uptake decreased. After filtration the filtrate was concentrated to ± 40 g. 40 ml of 5M hydrochloric acid were added while cooling with ice and the mixture was stirred for 30 minutes. A white precipitate was filtered off and the filtrate was extracted with 3 x 50 ml of diethylether. The combined organic layers were dried over magnesium sulfate and evaporated, resulting in 6 g (0.036 moles, 45% yield) of 2-hydroxy-α-oxo-phenyl acetic acid as a brown oil. The structure was confirmed by ¹H and ³C NMR. The brown oil was vacuum distilled (120°C/1mmHg) to yield the lactone of 2-hydroxy-α-oxo-phenyl acetic acid (2,3-coumaranedione) as a yellow crystalline solid.

Synthesis of N.N'-ethylene diamine bis (α-carboxy-salicylidene) (step 3) 2.96 g (0.02 mole) of 2,3-coumarandione and 0.80 g (0.02 mole) of sodium hydroxide were dissolved in 50 ml of water. In 5 minutes 0.60 g (0.01 mole) of ethylene diamine was added. Approximately 10 ml of ethanol were added to complete dissolution. After stirring at room temperature for 16 hours the mixture was evaporated leaving a yellow solid. 0.33 of the yellow solid was dissolved in the smallest amount of water and acidified with 4M hydrochloric acid. A white precipitate was filtered and dried, resulting in 150 mg (30% yield) of N.N'-ethylene diamine bis (α-carboxy-salicylidene).

Example 7

57.3 g of 2,3-coumarandione (0.387 mole) and 40.5 g of 50% NaOH solution (0.506 mole) were added to 700 g of water and heated to 80°C. After 30 min the lactone was completely hydrolyzed according to TLC. After cooling to room temperature 116.5 g of a 10% ethylenediamine solution (0.194 mole) were added. A solution of 32.28 g of MnSO₄.aq (0.191 mole) in 275 g water was added to the ligand solution and the reaction mixture was stirred at room temperature for 16 h while being aerated to accelerate the oxidation of Mn(ll) to Mn(lll). The Mn-chelate solution (pH 7.1) was filtered and spray-dried to give a yellow-brown Mn-chelate with the following structure. IR (KBr) 1631 cm ¹ (C=N)

Example 8

2.0 g of 2,3-coumarandione (13.5 mmole) and 1.4 g of 50% NaOH solution (17.5 mmole) were added to 25 g of water and heated to 80°C. After all the lactone had dissolved, the reaction mixture was cooled to room temperature. Subsequently, 5.0 g of a 10% 1 ,2-propyIenediamine solution (6.75 mmole) and a solution of 1.14 g of MnSO₄.aq (6.75 mmole) in 15 ml water were added. Stirring was continued overnight at room temperature in contact with air. The Mn-chelate solution was filtered and evaporated to dryness giving a yellow-brown Mn-chelate with the following structure. IR (KBr) 1634 cm ¹ (C=N)

Example 9

2.0 g of 2,3-coumarandione (13.5 mmole) and 1.4 g of 50% NaOH solution (17.5 mmole) were added to 25 g of water and heated to 80°C. After all the lactone had dissolved, the reaction mixture was cooled to room temperature. Subsequently, 5.0 g of a 10% 1 ,3-propylenediamine solution (6.75 mmole) and a solution of 1.14 g of MnSO₄.aq (6.75 mmole) in 15 ml water were added. Stirring was continued overnight at room temperature in contact with air. The precipitated Mn-chelate was filtered off and dried giving a dark green Mn-chelate with the following structure. IR (KBr) 1595 cm^"1 (C=N)

Example 10 2.0 g of 2,3-coumarandione (13.5 mmole) and 1.4 g of 50% NaOH solution (17.5 mmole) were added to 25 g of water and heated to 80°C. After all the lactone had dissolved, the reaction mixture was cooled to room temperature. Subsequently, 7.7 g of a 10% 1 ,2-cyclohexanediamine solution (6.75 mmole) and a solution of 1.14 g of MnSO₄.aq (6.75 mmole) in 15 ml water were added to give a turbid reaction mixture. Stirring was continued overnight at room temperature in contact with air. The precipitated Mn-chelate was filtered off and dried giving a yellow Mn-chelate with the following structure. IR (KBr) 1601 cm^"1 (C=N)

The starting material [the sodium salt of 2-hydroxy-α-oxo-phenyl acetic acid] has a typical absorption at 1676 cm^*1 (C=O), which has completely disappeared from the spectra of all of these manganese chelates.

Claims

Claims:

1. A chelating agent of the formula:

wherein

X is (CR'₂)_mCOO^"M⁺ wherein R' is independently H or CH₃, m is an integer of 0-3, and M is selected from H, Na, K, and NH₄; and

Y is independently selected from H, OH, COOH, SO₃H, PO₃H₂, C1-4 alkyl, halogen,

CN, and NO₂.

2. The chelating agent of claim 1 wherein M is selected from Na, K, and NH₄.

3. The chelating agent of claim 1 or 2 wherein m is 2, or preferably 0.

4. The chelating agent of any one of claims 1-3 wherein both aromatic OH groups are in the ortho position.

5. The chelating agent of any one of claims 1-4 wherein Y is selected from H, OH, COOH, SO₃H, and C1-4 alkyl, preferably from H and CH₃.

6. The chelating agent of claim 1 having the formula:

wherein both groups Y are H or CH₃, and M is H, or preferably Na, K or NH₄.

7. A composition comprising at least the chelating agent of any one of claims 1-6.

8. The composition of claim 7 further comprising a metal ion, preferably a manganese ion.

9. Use of the chelating agent of any one of claims 1-6 to combat metal ion deficiency, preferably manganese ion deficiency in plant cultivation.

10. Use of the composition of claim 8 to combat manganese ion deficiency in plant cultivation.