Mixed-metal chelates and process for the preparation thereof

Mixed-metal chelates represented by the following general formula EQU CaM(III)EDTA(OH).xH.sub.2 O wherein M is a trivalent transition metal and x is 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, or 8 and a process for their preparation are disclosed. The process comprises the steps of a) reacting calcium hydroxide or calcium oxide, ethylenediaminetetraacetic acid, and a transition metal-containing material in an aqueous medium, optionally in the presence of an oxidant to convert any transition metal present in a divalent form to its trivalent form; and b) separating the formed mixed-metal chelate by filtration or evaporation. These mixed-metal chelates are useful as catalyst precursors and dietary supplements.

The present invention relates to mixed-metal chelates and a process for the
 preparation thereof.
 BACKGROUND OF THE INVENTION
 Compositions containing two or more different metals have found use in
 several areas. Sometimes the compositions themselves can act as catalysts;
 more often, they behave as catalyst precursors, being transformed into
 active catalysts by reduction to give alloys or thin films or by oxidation
 (calcination) to give mixed-metal oxides. These oxides may behave as
 ceramics as well as catalysts. Often, these mixed-metal compositions are
 simple mixtures of single-metal compounds. Reduction or calcination of
 such mixtures can give non-homogeneous products because of incomplete
 mixing of the compounds, resulting in monometallic domains. When possible,
 it is advantageous to use as precursors unique compounds containing the
 desired metal ratio, because the metals will be intimately mixed, even at
 the molecular level.
 Mixtures of metals have other uses, as well. For example, iron, zinc, and
 magnesium are found in agricultural nutrient formulations, whereas iron,
 zinc, chromium, cobalt, and calcium are found in animal and human dietary
 supplements. Routinely, these sorts of formulations contain mixtures of
 compounds, each compound containing one of the desired metals. To reduce
 the amount of ancillary organic material in these formulations, it can be
 advantageous to provide two or more metals in a single compound, thereby
 increasing the percentage of metals vis-a-vis the organic ligands.
 Iron chelates are a class of compounds that have found use in natural gas
 treating, photographic bleaching, fertilizers, and dietary supplements.
 Routinely, said iron chelates are used as ammonium or alkali metal salts.
 In such cases, the alkali metal or ammonium ion provides charge balance
 but otherwise imparts no useful properties to the iron chelate. For
 example, sodium ferric ethylenediaminetetraacetate (NaFeEDTA) has been
 used for iron fortification in foods. The iron provided is beneficial, but
 the sodium is possibly hazardous to those people requiring a low-sodium
 diet. On the other hand, iron chelate complexes with calcium can
 potentially be used to provide the dietary benefits of both metals.
 Because of its tetravalent nature, ethylenediamine-tetraacetic acid (EDTA)
 can conceivably combine with a divalent and a trivalent metal to form
 complexes of the general formula M(II)M'(III)EDTA(OH).xH.sub.2 O. To our
 knowledge no such mixed-metal complexes of EDTA have been reported in the
 literature.
 The calcium salt of the ferric chelate of a similar ligand,
 hydroxyethylethylenediaminetriacetate (HEDTA), was reported as an
 amorphous, red solid (without analytical data) by Schugar, et al. in J.
 Amer. Chem. Soc., 89, 3712 (1967).
 There is clearly a need for transition metal chelate, particularly iron
 chelate, complexes with calcium which can be used to provide the dietary
 benefits of both metals.
 The present invention offers such transition metal chelate complexes with
 calcium and a process for their preparation.
 SUMMARY OF THE INVENTION
 In one aspect the present invention relates to mixed-metal chelates
 represented by the following general formula
EQU CaM(III)EDTA(OH).xH.sub.2 O
 wherein M is a trivalent transition metal and x is 0, 0.5, 1, 1.5, 2, 2.5,
 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, or 8.
 In another aspect the present invention relates to a process for preparing
 mixed-metal chelates of the general formula CaM(III)EDTA(OH).xH.sub.2 O,
 wherein M is a transition metal and x is 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5,
 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, or 8, said process comprising the steps of
 a) reacting calcium hydroxide or calcium oxide, ethylenediaminetetraacetic
 acid, and a transition metal-containing material in an aqueous medium,
 optionally in the presence of an oxidant to convert any transition metal
 present in a divalent form to its trivalent form; and b) separating the
 formed mixed-metal chelate by filtration or evaporation.
 DETAILED DESCRIPTION OF THE INVENTION
 In the context of the present invention, the general formula
 CaM(III)EDTA(OH).xH.sub.2 O is an empirical formula and is intended to
 include structures of higher nuclearity, such as, for example, Ca.sub.2
 [M(III).sub.2 (EDTA).sub.2 O].xH.sub.2 O. The amount of water of
 hydration, "x", is dependent both on M and the conditions of preparation.
 For the purposes of this invention, the term transition metal includes the
 metals of the lanthanide series. The transition metal contemplated by the
 foregoing general formula may be any transition metal that can obtain a
 stable trivalent state, including, but not limited to, iron, manganese,
 cobalt, chromium, yttrium, and ruthenium. Iron is preferred.
 The general reaction process comprehends the production of a mixed-metal
 chelate of the general formula CaM(III)EDTA(OH).xH.sub.2 O, wherein M is a
 trivalent transition metal and x is as defined hereinbefore, by the steps
 of a) reacting calcium hydroxide or calcium oxide,
 ethylenediaminetetraacetic acid, and a transition metal-containing
 material in an aqueous medium, optionally in the presence of an oxidant to
 convert any transition metal present in a divalent form to its trivalent
 form; and b) removing water by evaporation.
 In a straightforward reaction, a water-soluble salt of the trivalent
 transition metal is reacted with calcium hydroxide and EDTA according to
 the following equation:
EQU 2MX.sub.3 +5Ca(OH).sub.2 +2H.sub.4 EDTA.fwdarw.2CaMEDTA(OH)+3CaX.sub.2
 +8H.sub.2 O (1)
 wherein M is a transition metal, X is an inorganic or organic anion and
 H.sub.4 EDTA is used to distinguish the free acid from the tetraanion.
 When the calcium salt of X.sup.- is soluble (e.g., X.sup.- is Cl.sup.-,
 NO.sub.3.sup.-, CH.sub.3 COO.sup.-), the bimetallic complex can, in
 principle, be separated by precipitation or crystallization. When the
 complex is crystallized from aqueous solution, water may be included in
 the crystals, either bound directly to one or both of the metals or held
 in by lattice forces. The amount of water of crystallization will be
 dependent on solution pH, temperature, and the metals, among other things.
 Sometimes water can be driven off at high temperature or under vacuum,
 providing other stoichiometric hydrates or anhydrous materials.
 Many transition metals (e.g., Fe, Co, Mn, Ru, etc.) form stable divalent
 ions as well as trivalent ones. With the addition of an oxidant, the
 divalent salts of these metals can also be reacted with calcium hydroxide
 and EDTA to give the same type of bimetallic product:
EQU MX.sub.2 +2Ca(OH).sub.2 +H.sub.4 EDTA+1/2H.sub.2
 O.sub.2.fwdarw.CaMEDTA(OH)+CaX.sub.2 +4H.sub.2 O (2)
 Because of its powerful chelating ability for many transition metal ions,
 aqueous slurries of EDTA are often able to dissolve metal oxides. For
 example, partially ammoniated slurries of EDTA are commonly reacted with
 Fe.sub.3 O.sub.4 to form ferric EDTA solutions used in the photographic
 industry. Metal oxides can likewise be used to prepare CaMEDTA(OH)
 solutions according to the following reactions:
EQU MO+Ca(OH).sub.2 +H.sub.4 EDTA+1/2H.sub.2
 O.sub.2.fwdarw.CaMEDTA(OH)+3H.sub.2 O (3)
EQU M.sub.2 O.sub.3 +2Ca(OH).sub.2 +2H.sub.4 EDTA.fwdarw.2CaMEDTA(OH)+5H.sub.2
 O (4)
EQU M.sub.3 O.sub.4 +3Ca(OH).sub.2 +3H.sub.4 EDTA+1/2H.sub.2
 O.sub.2.fwdarw.3CaMEDTA(OH)+8H.sub.2 O (5)
 wherein M is a transition metal.
 Oxidants other than hydrogen peroxide may be employed. A potential
 advantage to the metal-oxide route is that there is no concomitant
 formation of calcium salt by-products.
 The elemental transition metal may also be used. EDTA will chelate the
 metal and oxidize it to the divalent state; another oxidant can complete
 the oxidation to the trivalent state:
EQU M+Ca(OH).sub.2 +H.sub.4 EDTA+1/2H.sub.2 O.sub.2.fwdarw.CaMEDTA(OH)+H.sub.2
 +2H.sub.2 O (6)
 Inasmuch as calcium oxide is converted to calcium hydroxide in aqueous
 medium, the oxide may replace the hydroxide as the calcium source. The
 transition metal may be any one that can obtain a stable trivalent state,
 including, but not limited to, iron, manganese, cobalt, chromium, yttrium,
 and ruthenium. The transition metal-containing material may be the
 elemental metal, a salt, an oxide, or a hydroxide. For example, iron may
 be introduced as iron metal, ferric chloride, ferric nitrate, ferric
 acetate, ferric citrate, ferrous sulfate, ferrous perchlorate, ferrous
 oxide, ferric oxide, ferrosoferric oxide, or ferric hydroxide.
 Preferably, the transition metal-containing material will be an oxide or
 hydroxide. As can be seen from an inspection of Equations 1-5, above, the
 use of a metal salt requires an excess of calcium hydroxide, relative to
 the transition metal, in order to bind the anions of the salt, resulting
 in a calcium salt by-product which must be separated from the desired
 calcium/transition metal/EDTA compound. Use of the elemental transition
 metal also obviates the need for excess calcium hydroxide, but results in
 the generation of flammable hydrogen gas.
 The molar ratio of EDTA to transition metal can be from about 0.75 to about
 1.25, but preferably from 0.9 to 1.1, and more preferably from 0.99 to
 1.01. An excess of EDTA or transition metal will result in unreacted
 material which must be separated from the desired product. The optimum
 molar ratio of calcium hydroxide (or oxide) to transition metal is
 dependent on the transition metal-containing reactant. If said reactant is
 a salt of a trivalent transition metal, the calcium hydroxide:transition
 metal ratio can be from about 2.0 to about 3.0, preferably 2.3 to 2.7, and
 more preferably from 2.45 to 2.55. If said reactant is a salt of a
 divalent transition metal, the calcium hydroxide:transition metal ratio
 can be from about 1.0 to about 3.0, preferably 1.5 to 2.5, more preferably
 1.9 to 2.1. If said reactant is an elemental metal, oxide or hydroxide,
 the calcium hydroxide:transition metal ratio can be from about 0.5 to 1.5,
 preferably from 0.7 to 1.3, more preferably from 0.9 to 1.1. Again, the
 most preferable ratio results in the least unreacted staring material.
 When the transition metal-containing material contains the transition metal
 in a lower-valent state than trivalent (for example, cobaltous chloride or
 iron metal), the resulting product can be converted to the desired
 trivalent complex by contacting the mixture with an oxidizing agent. The
 oxidizing agent need only be a more powerful oxidant than the trivalent
 transition metal. A practitioner skilled in the art will be able to
 determine if an oxidant has the desired oxidizing strength from tables of
 thermodynamic data. Useful oxidants include, but are not limited to,
 persulfates (e.g., ammonium persulfate or sodium persulfate); periodates
 (e.g., potassium periodate); permanganates (e.g., potassium permanganate);
 hypochlorites (e.g., sodium hypochlorite); hydrogen peroxide; and oxygen.
 Hydrogen peroxide and oxygen are especially preferred, due both to low
 cost and to the fact that neither introduces counterions to complicate the
 reaction mixture.
 In some cases, the desired calcium/transition metal/EDTA compound will have
 low solubility in water. In such cases, it is only necessary to filter the
 reaction mixture to obtain the product. If the product is more soluble in
 water, it can still be removed by crystallization, either by evaporating
 the water or by adding a co-solvent in which the product is less soluble.
 In cases where there are no other calcium salts present (i.e., the
 transition metal-containing reactant was the element or an oxide or
 hydroxide), the product can be obtained by spray-drying or otherwise
 removing all the water.
 The amount of water of crystallization in the calcium/transition metal/EDTA
 compound will vary depending on the transition metal, the pH, and the
 nuclearity of the complex. The water of crystallization can be removed to
 a desired degree by heating the compound and/or placing it under a vacuum.
 Such processes are well-known in the art.
 The mixed-metal chelates of the present invention are useful as catalyst
 precursors and dietary supplements.
 The invention will be further clarified by a consideration of the following
 examples, which are intended to be exemplary of the present invention and
 should not be construed to limit its scope in any way.

EXAMPLE 1
 A two-liter beaker was charged with ethylenediaminetetraacetic acid
 (H.sub.4 EDTA, 146 g, 0.500 mole); Ca(OH).sub.2 (92.6 g, 1.25 mole); and
 water (1400 g). The resulting mixture was stirred vigorously; and a
 solution of Fe(NO.sub.3).sub.3 (11.1%Fe by weight) was added quickly
 (251.5 g, 0.500 mole Fe) to the slurry, immediately giving a dark red
 solution. The solution was stirred for ten minutes at 45.degree. C. and
 filtered through a 1.2.mu. nylon filter. The filtrate was allowed to
 evaporate at 70.degree. C. for three days, after which large, red crystals
 of CaFeEDTA(OH).6.5H.sub.2 O were removed (82.1 g, 0.158 mole, 31.7%
 yield). The composition was determined by elemental analysis. Calc.
 (Found) for CaFeEDTA(OH).6.5H.sub.2 O: C 23.18%(23.01%); H 5.06%(5.27%); N
 5.41%(5.41%); Fe 10.78%(10.58%); Ca 7.73%(7.71%).
 EXAMPLE 2
 A one-liter beaker was charged with H.sub.4 EDTA (73 g, 0.25 mole);
 Ca(OH).sub.2 (46.3 g, 0.625 mole); and water (700 g). The mixture was
 stirred vigorously; and to it was added at once a solution of FeCl.sub.3.
 6H.sub.2 O (67.6 g, 0.250 mole) in water (120 g). The resulting brown
 slurry was heated to 90.degree. C., producing a dark, red-brown solution.
 Trace insolubles were filtered out, and the filtrate was allowed to
 evaporate at 65.degree. C. overnight. The product was removed from the
 mixture by filtration as small, red crystals (12.1 g, 0.023 mole, 9.3%).
 EXAMPLE 3
 A two-liter, five-necked, round-bottomed flask fitted with a pH probe, a
 thermometer, and a mechanical stirrer was charged with H.sub.4 EDTA (379
 g., 1.30 mole); Ca(OH).sub.2 (48.2 g, 0.650 mole); commercial Fe.sub.3
 O.sub.4 (69% Fe by weight, 100 g, 1.24 mole Fe); and water (1200 g). The
 slurry was stirred vigorously and heated to 93.degree. C. over one hour,
 during which time the slurry changed color from black to green. The
 mixture was cooled to 56.degree. C. over fifty minutes; and Ca(OH).sub.2
 was added to bring the pH up to 5.4 (24 g, 0.324 mole). During the
 addition, the green slurry became a deep red solution and then a red
 slurry. The slurry was sparged with air for three hours, and then more
 Ca(OH).sub.2 was added to bring the pH up to 5.9 (17.7 g, 0.239 mole). The
 crimson, crystalline product was removed by filtration and air-dried to
 give 508 g (0.980 mole, 80.8% yield (based on Ca)). The microcrystalline
 product was shown to be the same as the product in Example 1 by elemental
 analysis. Found: C 23.03%; H 5.28%; N 5.46%; Fe 10.68%; Ca 7.69%.
 EXAMPLE 4
 A 500-ml, three-neck flask, fitted with an overhead mechanical stirrer and
 thermometer was charged with H.sub.4 EDTA (58.5 g, 0.200 mole);
 Ca(OH).sub.2 (14.8 g, 0.200 mole); and water (350 ml). Vigorous stirring
 was begun; and Fe powder (11.2 g, 0.200 mole) was added. The resulting
 mixture was heated to 80.degree. C. to initiate reaction, and then
 stirred, open to the atmosphere, for four days. The resulting dark red
 solution displayed a small amount of residual ferrous ion, so 30% aqueous
 H.sub.2 O.sub.2 was added (0.1 g, 1 mmole). Filtration of the mixture gave
 CaFeEDTA(OH).6.5H.sub.2 O as fine, red-orange crystals (31.5 g).
 Evaporation of the filtrate at 65.degree. C. for one day resulted in the
 precipitation of another 17.5 g as large, red crystals. Total yield 49 g
 (0.0945 mole, 47%).
 EXAMPLE 5
 A 2.0046-gram sample of the product from Example 3 (3.868 millimoles) was
 placed in a Petri dish and set in an oven at 115.degree. C. for three
 days. The resulting tan powder was shown to be CaFeEDTA(OH) by elemental
 analysis. Calc. (Found): C 29.94% (29.90%); H 3.27% (3.32%); N 6.98%
 (7.01%); Fe 13.92% (14.19%); Ca 9.99% (10.02%). The yield was 1.5307 g
 (3.816 mmoles).
 EXAMPLE 6
 A one-liter beaker was charged with H.sub.4 EDTA (73.1 g, 0.250 mole);
 Ca(OH).sub.2 (37.0 g, 0.500 mole); and water (400 g). The mixture was
 stirred rapidly, and to the resulting slurry was added a solution of
 Co(NO.sub.3).sub.2. 6H.sub.2 O (72.7 g, 0.250 mole) in water (300 g). The
 resulting mixture was warmed gently to give a purple solution. To this was
 added dropwise 30% aqueous H.sub.2 O.sub.2 (14.2 g, 0.125 mole), causing a
 mild exotherm and darkening of the solution. The solution was stirred for
 one hour and then filtered to remove a small amount of brown, insoluble
 material. The solution was allowed to evaporate at 65.degree. C. for four
 days, after which purple crystals of CaCoEDTA(OH).5.5H.sub.2 O. (36.5 g,
 0.072 mole). The composition was determined by elemental analysis. Calc.
 (Found) for CaCoEDTA(OH).5.5H.sub.2 O: C 23.86% (24.53%); H 4.81% (5.00%);
 N 5.57% (5.86%); Ca 7.96% (8.63%); Co 11.71% (11.62%).
 EXAMPLE 7
 A 1.0982-g sample of CaCoEDTA(OH).5.5H.sub.2 O (2.182 mmoles) was placed in
 a Petri dish and heated at 105.degree. C. for three hours, giving 0.8299 g
 of CaCoEDTA(OH) (2.053 mmoles) as a pink powder.
 EXAMPLE 8
 A one-liter beaker was charged with H.sub.4 EDTA (73.1 g, 0.250 mole);
 Ca(OH).sub.2 (46.3 g, 0.625 mole); and water (450 g). The mixture was
 stirred rapidly, and to the resulting slurry was added a solution of
 CrCl.sub.3. 6H.sub.2 O (66.6 g, 0.250 mole) in water (250 g). The
 initially green mixture quickly became a blue-violet slurry, which was
 stirred another half-hour. The product, CaCrEDTA(OH).7H.sub.2 O, was
 removed by filtration, washed with water (500 g), and air-dried at
 40.degree. C., giving 92.9 g. Elemental analyses show that the product
 contained a by-product wherein some of the calcium had been replaced with
 chromium. Calc. for CaCrEDTA(OH).7H.sub.2 O: C 22.95%; H 5.20%, N 5.35%;
 Ca 7.66%; Cr 9.93%. Calc. for Ca.sub.0.85 Cr.sub.1.15 EDTA(OH).7H.sub.2 O:
 C 22.87%; H 5.18%; N 5.33%; Ca 6.49%, Cr 11.39%. Found: C 22.50%; H 5.34%;
 N 5.23%; Ca 6.55%; Cr 11.63%.