ES2222799B1 - "PROCEDURE FOR THE CHEMICAL FIXATION OF HOMOGENEOUS CATALYSTS TO INORGANIC SOLID SUPPORTS, PRODUCTS OBTAINED AND APPLICATIONS OF THE SAME". - Google Patents

Abstract

Procedure for the chemical fixation of homogeneous catalysts to inorganic solid supports, products obtained and applications thereof. Said process essentially comprises the following steps: - subjecting an inorganic solid support to an activation treatment; - functionalize the activated inorganic solid support from the previous stage; - anchoring said homogeneous catalyst to the support from the previous stage, establishing a chemical bond through the functionality introduced thereon. A useful product is obtained as a heterogeneous catalyst, as an ion exchange resin and as an active ingredient of drugs among other possible applications.

Description

Procedure for chemical fixation of Homogeneous catalysts to inorganic solid supports, products obtained and applications thereof.

Technical Field of the Invention

Homogeneous catalysis has allowed to develop at the academic level, and at the laboratory level, procedures for great difficulty, relevance and sophistication with a high degree of improvement thanks to the use of homogeneous catalysts of high cost, which normally cannot be recovered later of its use, which makes them unfeasible at the level industrial.

In this context, the present invention is falls within the technical field of the processes destined to fix the homogeneous catalysts to an inorganic support to facilitate recovery and subsequent reuse.

In other words, the present invention provides, more specifically, a procedure for "heterogeneization" of homogeneous catalysts by chemical fixation thereof to an inorganic solid, which acts as support, allowing its easy recovery at the end of process and its subsequent reuse, which allows profitability considerably the use of these expensive catalysts, making them viable industrially.

State of the art prior to the invention

Homogeneous catalysis has covered in all three recent decades very important academic goals achievable to laboratory scale, although only a very small number of processes could be transferred on a commercial scale.

In this sense, the important contribution of the Wilkinson catalysts [J.A. Osborne, F.H. Jardine, J.F. Joung and G. Wilkinson, J. Chem. Soc., A 1711 (1966)] that allowed catalytic hydrogenation of alkenes using the complex of Rhodium-triphenylphosphine: RhCl (PPh) 3.

The Nobel Prize in chemistry in the 1973, this discovery shows the importance of it, due both to the possibility of its application with others noble metals: Os, Ir, Pt, Pd, Ru, etc., as to their extension at Asymmetric induction hydrogenation reactions.

Indeed, the synthesis of chiral phosphines and their application to the preparation of organometallic complexes, capable of inducing chirality in hydrogenation processes, has led to very important successes, so that in the nowadays it is possible to achieve the enantioselective synthesis of almost any molecule, but always on a laboratory scale. He high cost of chiral "ligands" necessary to build the chiral catalyst, and the cost of noble metal itself necessary (Os, Go, Pt, Pd, Ru, Rh etc.) has done that, until the moment, only a very small number of processes, if compared with the huge bibliography about it, find application commercial.

Among these, the synthesis of the L-DOPA, or 3,4-dihydroxyphenylalanine,  drug used in the treatment of Parkinson's disease, tuned by Knowless [W. S. Knowless, M. J. Sabcky and VB. D. Vineyard, J. Chem. Soc., Chem. Comm., 10 (1972)] and marketed by Monsanto in 1974. This success was associated with the employment of complex [Rh ((R, R) -diPAMP) COD] BF_ {4}, in the which is used as ligand DiPAMP, a chiral diphosphine, which allowed to achieve what has been recognized as "first process industrial that uses asymmetric catalysis ".

Another important example of asymmetric catalysis homogeneous is the synthetic route that leads to the obtaining L-menthol, one of the most important substances widely used as a food additive or perfumery.

This process has been developed by the company Takasago Int. Corp., Japan that produces 1500 tons / year, which currently represents the world's largest production of a product using asymmetric catalysis. In this process the homogeneous catalyst [Rh - (-) - BINAP (COD)] ClO_ {4}, which enables enantioselective isomerization of an allyl amine to the corresponding (R) - (-) - diethyl- (E) -citronelalenamine, creating, in the global process the three chiral centers specific that provide the characteristic smell of this molecule [H. U. Blazer, F. Spindler and M. Studer, Appl. Catal. A: Gen, 221, 119 (2001)]. The ligand used, based on diphosphine BINAP (or 2,2'-bis (diphenylphosphino) -1,1'-binaphthyl) It is one of the most useful so far, among the available (for example, PAMP, DiPAMP, DIOP, CHIRAPHOS, etc., all of them defined in the literature referring to the synthesis of complexes organometallic, well known to experts in the field) since the difficulty of turning the link between the two fragments Binaphthyl gives it high chirality. Its synthesis is due to Noyori [H. Nozaki, S. Moriuti, H. Takaya and R. Noyori, Tetrahedron Lett., 5239 (1966)], who has successfully applied it, both in form from Rh-BINAP, to very diverse processes of chiral hydrogenation of olefins in esters or acids α- (acylamino) acrylics, as forming complexes of Ruthenium, Ru (II) -BINAP, exceptionally useful in the enantioselective hydrogenation of α acids, β- and β, γ-unsaturated.

In this sense, the production of industrial anti-inflammatory scale no Steroid, (S) - (+) - Naproxen, using as homogeneous chiral catalyst [Ru (OAc) 2 ((S) -BINAP)].

It is also possible to effect hydrogenation of carbonyl groups, in aldehyde and ketone groups, with catalysts homogeneous Ru, which by incorporating BINAP make it enantioselective. Thus, hydrogenation is described chiral of a large variety of ketones using [RuX (sand) BINAP] X or [RuX_ {2} (BINAP)], X being any halogen. For example, the antibacterial agent "Levofloxacin" is obtained at scale industrial by this procedure.

It gives an idea of the importance that currently the international scientific community grants homogeneous catalysis asymmetric, the fact of the awarding of the Nobel prizes of Chemistry of the year 2001, to the scientists mentioned above, William S. Knowles and Ryoji Noyori, as well as Professor K. Barry Sharpless, whose research has focused on epoxidations enantioselectives of olefins, using various agents of chiral induction, such as diethyl tartrate.

Following this technique is produced in a way enantioselective, on an industrial scale, glycidol, an intermediate necessary for the production of certain drugs β-blockers [H. C. Kolb, K. B. Sharpless, in  Transition Metals in Organic Synthesis, Cap. 2, VCH Manheim, 1998].

However, despite the successes described in laboratory level, when trying to move to scale industrial discoveries made in homogeneous catalysis, most of them are commercially unfeasible by the difficulty or inability to recover the catalysts in Conditions to be reused again.

Precisely, heterogeneous catalysis, comparatively less selective than the homogeneous one, find here its main advantage, which justifies its wide use in the practically all the catalyzed processes of chemistry industrial.

Hence, at this time, it is considered a challenge of the greatest scientific and economic importance, find suitable procedures for the heterogeneization of reactions carried out with more interesting homogeneous catalysis, of so that by allowing catalyst reuse, it is achieved make them viable from an economic point of view.

Currently, to get the heterogeneization of the various homogeneous catalytic systems, ongoing investigations focus primarily on two types of strategies, namely, at the catalyst junction homogeneous to an organic polymer, or in the union thereof to a inorganic support.

In the first case, the strategy followed is based in the use of synthetic polymers, which in some way, bind the complex to the polymeric lattice, either by a link covalent, or simply adsorb or retain it physically. Be deals with polymers of the Merrifield type, based on polystyrene crosslinked, polyacrylates or polypeptides, to which they bind very various complexes, including very varied chiral phosphines. [C. Saluzzo, R. Halle, F. Touchard, F. Fache, E. Schulz and M. Lemaire, J. Organometal. Chem., 603, 30 (2000)]. The employment of this type of heterogeneized catalysts on polymeric supports requires a very careful selection of both the solvent and the operating conditions, since these variables may affect, of important form, to the mechanical properties of the polymer, being This is one of the main limitations of the method. However, it is possible to have reagents commercially available today chiral, such as BINAP, precursor of organometallic complexes chiral, linked to polymeric supports. Thus, FLUKA offers (no. catalog: 10885) a cross-linked polystyrene matrix with DVB, 1%, to which it is "linked" (R) - (+) - BINAP, (0.4 mmol / g), with which you can prepare various organometallic complexes, usable in chiral hydrogenations [D. J. Bayston et al., J. Org. Chem., 63, 3137 (1998)].

In the second case, the strategy corresponding to the use of inorganic supports has received, so far, much less attention from the researchers. In general, most published studies are based on the use of silica as a support, and on the use of various organosilanes as binding agents between the support and the corresponding complex [A. J. Sandee, J. N. H. Reek, P. C. J. Kamer and P. W. N. M. Van Leeuwen, J. Am. Chem. Soc., 123, 8468 (2001)]. The limitations of this procedure are due fundamentally, to the fragility of the links carbon-silicon, which are susceptible to suffer various substitution processes, including hydrolysis, when Use water as a solvent.

There is, therefore, currently a clear awareness of the need to develop new methods for the "heterogeneization" of homogeneous catalysts. Within the context of the present invention, they are considered included under the name "homogeneous catalyst" both "coordination complexes" such as "complexes organometallic. "

The present inventors have directed their research efforts in this field, which has led them to discover a new procedure that allows covalent binding of various complexes to any support of inorganic nature. This discovery has allowed the achievement of this invention, which is set forth in detail in the following sections of this specification.

Detailed description of the invention

The present invention, as indicated in its statement refers to a procedure for fixing Chemistry of catalysts homogeneous to inorganic solid supports, to the products thus obtained and to the applications of the same.

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More specifically, the procedure of the The present invention is characterized in that it essentially comprises the following stages:

(to)

submit a inorganic solid support to an activation treatment;

(b)

functionalize the solid support inorganic activated from the previous stage;

(C)

anchor said homogeneous catalyst to support from the previous stage, establishing a link chemical through the functionality introduced on the same.

The activation stage (a) comprises essentially the deposition of an aluminum orthophosphate layer amorphous (AlPO_4) on said inorganic solid support, in a minimum amount of 20% (p / p).

The step (b) of functionalization essentially comprises the introduction of a group of the formula -NH- (CH2) n -
NR2 (where n = 2-6 and R = hydrogen or 2-pyridylmethyl), by means of phosphonamide bonds, inorganic-organic hybrids, of high strength.

For the introduction of the previous group it is done react the activated inorganic support with an alkylenediamine of formula H 2 N- (CH 2) n -NH 2  (where n = 2-6) to get support functionalized where R is hydrogen. Then, if desired, the R = groups are introduced 2-pyridylmethyl.

The anchoring stage (c) essentially comprises the reaction of the functionalized support, as ligand, with the metal of a coordination complex or an organometallic complex or salt metallic to form the desired product.

To carry out the procedure of the The present invention can be used as an inorganic solid support any of those commonly used as metal supports in heterogeneous catalysis, since they are interested precisely in having the same properties of these: high outer surface and be inert enough not to generate side reactions. So, the most commonly used are alumina, silica or carbon active, but any other, than one at Previous properties, its low price. This is the case of the sepiolite, a natural hydrated magnesium silicate, of nature fibrous and high surface. About any of these solids an outer layer of AlPO_ {4} must be deposited which makes it acquire the physicochemical properties of this compound. In fact, amorphous aluminum orthophosphate itself can constitute by itself a suitable inorganic solid support within the scope of the present invention.

Amorphous aluminum orthophosphate is a solid inorganic, high surface area and high number of centers surface acids, coming from superficial "defects" of the three-dimensional network "-P-O-Al-" that while in his set is neutral, locally presents on its surface, both acid centers, coming from bonds -P-O-H, as of basic centers, due to the corresponding links Al-O-H This number is very variable, depending on the synthesis method used: temperature, pH, speed, order of addition of reagents, etc. In this meaning, the best results are obtained using the method that in the scientific literature it is called solgel.

The use of this type of solids, for heterogeneization of homogeneous catalysts is completely unpublished and original.

For the functionalization of inorganic support any phosphonamide bond formation can be used any alkylenediamine of formula H 2 N- (CH 2) n -NH 2 (where n = 2-6). They can be cited as examples of such diamines ethylenediamine, 1,3-diaminopropane, 1,4-diaminobutane, etc. When R is 2-pyridylmethyl, the product is reacted anterior with picolyl chloride. An especially preferred case is one in which n is 2 and R is 2-pyridylmethyl, corresponding to ligand N, N'-bis (2-pyridylmethyl) ethylamine or bpea singular interest in the context of the present invention.

The metal carrier compound at the stage of anchored (c), as already indicated, can be selected from a coordination complex, an organometallic complex or a salt metallic, which can be defined generically by the formula general:

L_ {m} B_ {q} MX_ {p}

where L is a chiral ligand or not chiral, B is a chiral or non-chiral phosphine ligand, M is a transition metal, X is a halogen and m, q and p are integers (of 0 to 6) such that the electric charge is compensated

Ligand L is generally selected from group consisting of acetate, hydroxyl, water, chiral anions, amino acids, alkaloids, nicotine or any other ligand usually described in the specific bibliography well known for The experts in the field.

Ligand B is generally selected from group consisting of triphenylphosphine, diphenylphosphine, BINAP, PAMP, DiPAMP, DIOP, CHIRAPHOS or the like.

The metal M is generally selected from group formed by any transition metal especially Os, Go, Pt, Ru, Rh or Pd.

Halogen X is selected from chlorine, bromine and iodine.

The process of the invention as it is described above is illustrated in the following Scheme I:

Scheme I

one

The orthophosphate deposition stage of aluminum on the inorganic support can be carried out by any conventional known method, although as already mentioned the method called above is preferred sol-gel

More specifically, the authors of this invention, both in the Spanish patent P-9601847 / X, as in various publications scientists, show the excellent results they have obtained carrying out the reaction between aluminum trichloride hexahydrate and orthophosphoric acid, 85% by weight, at temperature constant of 0ºC, and raising the pH to 6.1, by adding a aqueous solution of ammonium hydroxide, producing the slow precipitation of amorphous aluminum orthophosphate.

AlCl_ {3} \ cdot 6H_ {2} O + H_ {3} PO_ {4} + 3NH_ {4} OH \ \ text {------------>} \ AlPO_ {4} + 3NH_ {Cl} + 9H 2 O

To get solid supports inorganic agents of the present invention, it is sufficient introduce the inorganic solid, usually particulate, into the previous reaction medium, whereby the precipitation of amorphous aluminum orthophosphate is produced on the particles of solid said. The inorganic solid will be introduced in an amount suitable for the final product obtained to contain at least one 20% by weight of deposited amorphous aluminum orthophosphate.

In the case of using only his own amorphous aluminum orthophosphate as an inorganic solid support in the procedure of the present invention is obviously not accurate the presence of any other inorganic support in the middle.

The precipitated aluminum orthophosphate thus obtained may require some subsequent treatment of conditioning, purification, etc., for example washing and drying, with the operating conditions preferred by the inventors being washing with isopropyl alcohol followed by drying at 120 ° C for 24 hours. The aluminum orthophosphate thus treated offers a large specific surface area, as well as a high number of surface acid centers, if it is subjected to calcination for 3 hours, at 350 ° C, where the NH4 Cl formed in the reaction of sublimation is eliminated
synthesis.

The functionalization reaction with a alkylenediamine leads to intimate homogenization of the supports activated with alkylenediamine in the presence of a minimum amount of inert organic solvent against the reaction. For carrying out said homogenization is especially preferred the use of the solvent at room temperature under conditions of "incipient moisture" (such "humidity" conditions incipient "are defined within the context of this invention as those conditions that allow homogenization of the mixture using the minimum possible amount of solvent). TO The solvent is then removed by evaporation. Next, the dry solid obtained is subjected to heating between 80-120ºC for the time necessary to ensure that the reaction with the support occurs in its full extent. TO then the reaction mixture is subjected to irradiation of microwave and, if necessary, cools and separates excess alkylenediamine by washing with a suitable solvent of functionalized support.

As an especially preferred solvent for homogenization diethyl ether is used and as a solvent especially preferred for the final washing step is preferred Ethanol

When R is 2-pyridylmethyl, it reacts the above product with picolyl chloride, preferably by homogenization under conditions of "incipient moisture" defined above, in the presence of a solvent inert to the reaction at a temperature comprised between 60-100 ° C in the presence of a base. One time After completion of the reaction, the product obtained is washed with a solvent  suitable and then dried.

As an especially preferred solvent for homogenization is used ethanol and as solvent especially preferred for the final wash step the ethanol.

The metal anchoring reaction can be carried carried out in a multiplicity of known reaction conditions by any expert in the formation of metal complexes. Depending on the nature of the compound of formula L_ {m} B_ {q} MX_ {p} it will be necessary to use conditions particular: for example, if the compound mentioned is sensitive to water or the compound to be obtained is also the conditions they will be anhydrous; if they were sensitive to oxygen, a inert atmosphere; and the like

A particularly preferred case is that in that R is hydrogen, and the anchoring reaction is carried out with the compound [Ru II (PPh 3) 3 Cl 2] (corresponding to the general formula L_ {m} B_ {q} MX_ {p} where m is 0, B is triphenylphosphine, q is 3, M is Ru II, X is chlorine and p is 2), with the elimination of one molecule of HCl for each molecule fixed on the support, obtaining a final product represented by the formula:

solid \ inorganic // AlPO_ {4} // PO_ {3} -NH- (CH_ {2}) {n} -NH_ {2} - [Ru II} (PPh 3) 3 Cl] Cl

Preferably the above reaction is performed. in the dry phase with microwave irradiation.

Another particularly preferred case is that in that R is hydrogen, and the anchoring reaction is carried out with RuCl 3 (corresponding to the general formula L_ {m} B_ {q} MX_ {p} where m is O, q is O, M is Ru, X is chlorine and p is 3), in the presence of a reaction inert solvent, of a base, a salt of lithium and triphenylphosphine, obtaining a final product represented by the formula:

solid \ inorganic // AlPO_ {4} // PO_ {3} -NH- (CH_ {2}) {n} -NH_ {2} - [Ru II} (PPh 3) 3 Cl] Cl

Another particularly preferred case is that in that R is hydrogen, and the anchoring reaction is carried out with a compound of general formula L_ {m} B_ {q} MX_ {p} (where M is Os, Go, Pt, Ru, Rh or Pd, L is any ligand as defined above, and B is PPh3 any phosphine or diphosphine chiral, for example, BINAP, PAMP, DiPAMP, DIOP, CHIRAPHOS, or not chiral), in the presence of a reaction inert solvent, obtaining a final product represented by the formula:

solid \ inorganic // AlPO_ {4} // PO_ {3} -NH- (CH_ {2}) {n} -NH_ {2} - [ML_ {m} B_ {q} X_ {p-1}] X

Another particularly preferred case is that in that R is 2-pyridylmethyl, n is 2 and the reaction of anchored is carried out with RuCl 3 (corresponding to the formula  general L_ {m} B_ {q} MX_ {p} where m is O, q is O, M is Ru, X is chlorine and p is 3), in the presence of a solvent inert to the reaction, of a base, a salt of lithium and triphenylphosphine, obtaining a final product represented by the formula:

solid \ inorganic // AlPO_ {4} // PO 3 -NH- (CH 2) n -NR 2 - [Ru II (PPh 3) 2 Cl] Cl

Another particularly preferred case is that in that R is 2-pyridylmethyl, n is 2 and the reaction of anchored is carried out with a compound of general formula L_ {m} B_ {q} MX_ {p} (where M is Os, Ir, Pt, Ru, Rh or Pd, L is any ligand as defined above, and B is PPh_ {3} any chiral phosphine or diphosphine, for example, BINAP, PAMP, DiPAMP, DIOP, CHIRAPHOS, or non-chiral), in the presence of a solvent inert to the reaction, obtaining a final product represented by the formula:

solid \ inorganic // AlPO_ {4} // PO_ {3} -NH- (CH_ {2}) {n} -NR_ {2} - [ML_ {m} B_ {q} X_ {p-1}] X

Another particularly preferred case is that in that R is 2-pyridylmethyl, n is 2 and the reaction of anchored is carried out with a complex Ru-Diphosphine, chiral or non-chiral.

Another particularly preferred case is that in that R is 2-pyridylmethyl, n is 2 and the reaction of anchored is carried out with RuCl 3 (corresponding to the general formula L_ {m} B_ {q} MX_ {p} where m is 0, q is 0, M is Ru, X is chlorine and p is 3), in the presence of a solvent inert to the reaction, of a base, a lithium salt and of 1,2-bis (diphenylphosphine) ethane, obtaining a final product represented by the formula:

solid \ inorganic // AlPO_ {4} // PO_ {3} -NH- (CH_ {2}) {n} -NR_ {2} - [Ru II} (PPh 2 CH 2 CH 2 PPh 2) Cl] Cl

Another particularly preferred case is that in that R is 2-pyridylmethyl, n is 2 and the reaction of anchored is carried out with RuCl 3 (corresponding to the general formula L_ {m} B_ {q} MX_ {p} where neither is O, q is O, M is Ru, X is chlorine and p is 3), in the presence of a solvent inert to the reaction, from a base, a lithium salt and from BINAP, obtaining a final product represented by the formula:

solid \ inorganic // AlPO_ {4} // PO_ {3} -NH- (CH_ {2}) {n} -NR_ {2} - [Ru II} (BINAD) Cl] Cl

In general the previous anchoring reactions are likely to be performed in one or several steps with or without isolation of intermediate products.

The process of the invention thus set forth, It aims to solve many of the problems indicated above, since: 1st) allows, in principle, to use as support any inorganic solid normally used in this type of Applications; 2nd) the binding of the complex catalyst molecule to inorganic support is established by a phosphoamide bond, comparatively much more stable than the various links Covalent described so far for the binding of compounds organic to inorganic matrices.

Both features show the undeniable advantages that the present invention brings to the situation defined by the state of the art, especially as which refers to the possibility of using a solid support inorganic of greater inert character and stability physicochemical (for example, minimal or null interaction with solvents and reagents under the conditions of work normally employed, etc.) than organic polymers. Thus, the present invention constitutes an important advance in the practical application of catalyst heterogeneization homogeneous, with respect to the methods currently known.

Another object of the present invention is constitute the products obtained through the procedure of the invention, which have been defined in detail to throughout the previous paragraphs.

Yet another object of the present invention is they constitute the different uses of said products. At its greatest These products have application as catalysts, especially as heterogeneous catalysts, and more particularly as heterogeneous catalysts in reactions that Normally they were carried out by homogeneous catalysis. A An example of this type of reactions is hydrogenation in the liquid phase of alkenes, alkynes and carbonyls to produce the corresponding alkanes, alkenes and alcohols.

Moreover, some of the products obtained in the process of the present invention, can present utility as ion exchange resins of inorganic nature, as is the case with

solid \ inorganic // AlPO_ {4} // PO 3 -NH- (CH 2) n -NR 2

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useful to recover different metals from ionic transition of dilute solutions, or very diluted, in which they are.

Also, some of the products obtained in The process of the present invention may present utility as active ingredients of drugs, as is the case from

solid \ inorganic // AlPO_ {4} // PO 3 -NH- (CH 2) n -NR 2

able to reduce cholesterol plasma through its ability to fix and remove (by evacuation) bile acids, thus inhibiting their absorption intestinal.

Embodiments of the invention

The present invention is further illustrated. through the following examples, which in no case should be considered restrictive of its scope, which will be defined solely and exclusively by the corresponding claim attached.

Example 1 Synthesis of supports functionalized by an alkylamino group terminal Preparation of aluminum phosphate and phosphate supports aluminum / sepiolite

The different supports were prepared leading to conduct the reaction between aluminum trichloride hexahydrate and the orthophosphoric acid, 85% by weight, at a constant temperature of 0 ° C, and raising the pH to 6.1, by adding aqueous solution of ammonium hydroxide, with the slow precipitation of solid amorphous

Said solid is washed with isopropyl alcohol and subsequently dried in an oven, at 120 ° C for 24 hours. Subsequently it is subjected to calcination in a muffle oven, for 3 hours, at 350 ° C, where NH4Cl is sublimation removed formed in the synthesis reaction. In this way you get a support of amorphous AlPO_ {4}.

On the other hand the previous process is repeated adding sepiolite (Tolsa S. A.) to the reaction medium in a amount corresponding to 80% of the final weight of the product obtained to obtain a support of AlPO4 / sepiolite.

Table 1 shows the surface values, S BET, measured by nitrogen adsorption, from the BET method, and the number of acidic and basic centers, determined by chemisorption with pyridine, dimethylpyridine and benzoic acid, both of the synthesized solids, as of the starting Sepiolite, in order to prove how the activation treatment, by " in situ " synthesis of the AlPO 4 radically changes the surface properties of the support, decuing it, or activating it, for the subsequent treatment.

TABLE 1 Surface area, S_ {BET} (m 2. g - 1) and properties Acid-Basics of solids used as supports, in (µm. g -1), which express the amount of titrating agent, fixed in monolayer, per gram of solid valued

Support S_ {BET} Acidity Basicity Pyridine Dimethylpyridine Ac. Benzoic AlPO_ {4} 211 200 249 352 Sepiolite 233 10 13 115 AlPO_4 / Sepiolite 139 198 128 393

Determination of surface acidity with Pyridine and dimethylpyridine is raised as a method, scientifically accepted, to discriminate Brönsted acidity, associated to the -OH groups, which are the ones that interest us, compared to the total acidity, sum of Brönsted and Lewis acid centers, which is the that values pyridine. The data in Table 1 clearly shows important values of P-O-H groups acids, in the pure AlPO4 and AlPO4 / Sepiolite solids. It is also easy to check the effectiveness of the treatment, as far as which refers to the large increase in surface acid centers experienced by Sepiolite after the incorporation of 20% of AlPO_ {4}.

Activation of aluminum phosphate, or phosphate, supports aluminum / sepiolite, by reaction with ethylenediamine

The reaction of surface acid groups of the supports with one of the amino terminal groups of the ethylenediamine, involves intimate homogenization, in a flask of 100 mL of 30 g of either of the two supports (AlPO4 or AlPO 4 / Sepiolite), 80 mL of ethyl ether and 4 mL of ethylenediamine, for one hour on rotary evaporator, at temperature ambient. These amounts provide the conditions that are denominated of "incipient humidity" that allow the homogenization of the mixture, using the minimum amount of solvent The ethyl ether is then removed without need vacuum, by heating the water bath in the same rotary evaporator, but without emptying, since it boils at 33 ° C. Next, the white and dry solid left in the flask, impregnated with reagent, undergoes heating of 100 ° C, in the same rotary evaporator, bringing the water bath to a boil. This operation is prolonged. for 90 minutes To ensure that the reaction with the support is carried out to its full extent, the flask is introduced into a domestic microwave oven, where it is subjected, for ten minutes, at progressive irradiation, 5 minutes in each of the two positions, at 190 and 380 W, respectively. Once cooled the flask, ethylenediamine that has not reacted is separated of the solid, for which it is washed with 100 ml ethanol three consecutive times, separating each time by vacuum filtration.

The experimental procedure to follow will be exactly the same when instead of ethylenediamine another diamine, for example, 1,3-propylenediamine, and Similar.

Example 2 Complex covalent immobilization [Ru II (PPh 3) 3 Cl] to the support AlPO_ {4}

The synthesis of the complex of Ruthenium triphenylphosphine, [Ru II (PPh 3) 3 Cl 2], is carried out very simply, according to the methodology normally used described in the bibliography. Thus, 0.2 g (0.82 are placed mmol) of RuCl 3 • H 2 O in a flask containing 15 mL of methanol and then 1.2 g (4.92 mol) of triphenylphosphine (PPh3) dissolved in 15 mL of methanol and heat to reflux for three hours in a water bath to boiling. The complex precipitates upon cooling, and is collected by plate filtration, where it is washed successively with methanol and ether ethyl. After drying under vacuum, 0.56 g of product are collected, 72% yield.

Once synthesized, the immobilization of said complex is produced by reacting it with the group amino free of support bound ethylamine. To do this, it 8 g of the support activated by the ethylenediamine (from Example 1), 5 mL of the solution that It contains the synthesized complex and 20 mL of ethanol, and is heated the mixture at reflux in a water bath for two hours. Past this time the solvent is evaporated in a rotary evaporator and subjected to microwave radiation, in the same flask where it was made the whole process. The treatment is carried out in a microwave domestic for ten minutes in two batches of 5 minutes each, in the positions that radiate at 190 and 380 W, respectively. A once the flask has cooled, it separates from the desired solid, the complex Ru II (PPh 3) 3 Cl 2] that has not reacted, for which a washing of the same is carried out with methanol, three consecutive times, with 15 mL, each time, where the solid is successively separated by vacuum filtration. Together the filtered ones, you can check, approximately, the quantity of complex that has been immobilized, comparing the speeds of the hydrogenation reactions obtained by using said filtered and obtained by using the solid with the complex immobilized.

The experimental procedure to follow will be exactly the same when instead of the complex [Ru II (PPh 3) 3 Cl 2], be used any other of the type (PPh_ {3}) n {ML_ {n} Cl_ {n}, where n is 1,2,3 etc., M any other noble metal, L any ligand, chiral or non-chiral, and PPh3, any phosphine or diphosphine, chiral or non-chiral.

Example 3 Synthesis of the complex [Ru II (bpea) (PPh 3) 2 Cl] Cl linked to support AlPO_ {4} Synthesis of ligand (bpea) anchored to support AlPO_ {4}

From the solid activated with ethylenediamine, or other terminal diamine, the functionalization of the hydrocarbon chain covalently linked to the support, by the reaction of the amino terminal group thereof with two molecules of picolyl chloride, which directly yields the ligand (bpea) or N, N'-bis- (2-pyridylmethyl) ethylamine, as expressed in Scheme II. To do this, start from 30 g of either of the two supports (AlPO_ {4} or AlPO_ {4} / Sepiolite) activated with ethylenediamine, according to the procedure described in the Example 1, which are arranged in a 250 mL flask with a solution of 4.5 g of picolyl chloride in 50 ml of ethanol from 96% (in variable quantity depending on the support, but of approximately 60 mL) until moisture conditions are achieved incipient. The homogenization of the mixture is carried out in the rotavapor, where the flask is rotated for half an hour, at room temperature. Then the temperature of the bath at 80-90ºC, and it is added, every 10 minutes, 2 ml of a solution of 2.5 g of NaOH in 15 ml of water. The approximate duration of the reaction is about 90 minutes at 80 ° C, developing an intense pink color during the course of it, which changes to light red once the reaction has ended and the reaction mixture has cooled. At that time, the solid formed is filtered and washed three times consecutive with 100 ml of ethanol, to remove excess picolyl, the solid being dried by vacuum filtration.

Synthesis of the complex [Ru II (bpea) (PPh 3) 2 Cl] Cl anchored covalently to support AlPO_ {4}

In this case we proceed to synthesize the complex homogeneous in the medium in which the ligand is present (bpea) anchored to the support. Thus, 8 g of the amorphous solid are taken AlPO4 containing said ligand, and kept under stirring for one hour with 0.4 g of RuCl 3 in a flask containing 10 mL of ethanol. Then and under argon atmosphere, it enter 0.118 g of LiCl and 0.192 mL of triethylamine, stirring the solution for thirty minutes. Finally, 0.869 are added g of triphenylphosphine (PPh3) and heated to reflux for two hours. Once cooled, 30 mL of methanol are added, filtered the solid, which is washed twice consecutively with. 30 mL of methanol,  meeting the three fractions of the wash to proceed with after the calculation of the amount of immobilized complex (by comparison between the catalytic activities of the complex immobilized in the solid and dissolved in the methanol of washed). The solid containing the Ru complex bound together Covalent, once dried by vacuum filtration, is ready to its use as a heterogeneous catalyst.

Example 4 Synthesis of complexes containing diphosphines, chiral and non chiral, of the type [Ru II (bpea) diphosphine-Cl] Cl, covalently linked to supports

Using exactly the same method as that of Example 3, for obtaining the complex [Ru II (bpea) (PPh_ {3}) Cl_ {2} anchored to support AlPO_ {4}, you can also immobilize any diphosphine, chiral or non-chiral, on any of the supports described in Example 1, on which ligand formation (bpea) has been performed.

Synthesis of the complex [Ru II (bpea) (PPh 2 -CH 2 -CH 2 -PP 2) Cl] Cl  bound to AlPO_ {4} / Sepiolite support

Thus, in this case we also proceed to synthesize the corresponding homogeneous complex with diphosphine, 1,2-bis (diphenylphosphine) ethane in the medium in which the ligand (bpea) anchored to the support AlPO_ {4} / Sepiolite. 8 g of the activated solid are taken with the ligand (bpea), which is prepared identically to that indicated in Example 3, and kept under stirring for one hour with 0.4 g of RuCl 3 in a flask containing 10 mL of ethanol. TO then, under argon, 0.118 g of LiCl is introduced and 0.192 mL of triethylamine, the solution being stirred for thirty minutes. Finally, 0.66 g of diphosphine is added, 1,2-bis (diphenylphosphine) ethane and se Heat at reflux for two hours. Once cooled, they are added 30 mL of methanol, the solid is filtered, which is washed twice consecutive with 30 mL of methanol, meeting the three fractions of washing for. proceed after the calculation of the amount of immobilized complex (by comparison between catalytic activities of the immobilized complex in the solid and the dissolved in the methanol wash). The solid that is fixed on Ru complex, once dried by vacuum filtration, is ready for use as a heterogeneous catalyst.

Synthesis of the chiral complex [Ru II (bpea) (BINAP) Cl] Cl linked to support AlPO_ {4}

Proceeding identically to the previous one and also starting with 8 g of AlPO4 activated with the ligand (bpea), prepared according to Example 3, is kept under stirring for one hour with 0.4 g of RuCl 3 in a flask containing 10 mL of ethanol. Then, under argon atmosphere it Enter 0.118 g of LiCl and 0.192 mL of triethylamine, stirring the Dissolution for thirty minutes. Finally, 1.03 g of chiral diphosphine [(R) - (+) - BINAP] or, (R) - (+) - 2,2'-bis (diphenylphosphino) -1,1'-binaphthyl, and It is heated at reflux for two hours. Once cooled, they are added 30 mL of methanol, the solid is filtered, which is washed twice consecutive with 30 mL of methanol, meeting the three fractions of washing to proceed after the calculation of the amount of immobilized complex (by comparison between catalytic activities of the immobilized complex in the solid and the dissolved in the methanol wash). The solid that contains the chiral complex of immobilized Ru, once dried by filtration at empty, it is ready for use as a catalyst heterogeneous.

Example 5 Determination of the catalytic activity of the different organometallic complexes of Ru synthesized, facing the Catalytic hydrogenation in liquid phase of different compounds organic

Although different physical techniques, such as ultraviolet spectroscopy of diffuse reflectance, or the infrared spectroscopy, show that the processes of covalent immobilization of the different species described in the Proposed examples, have been obtained satisfactorily, are considers it appropriate to proceed with the experimental evaluation of some of the synthesized Ru complexes, for different hydrogenation processes in order to better value the utility real of the invention.

The hydrogenation reactions have been carried out in a Parr Instrument Co., Model 3911 hydrogenator, under controlled hydrogen pressure, operating between 7 and 4 atmospheres, with methanol as solvent and at a constant temperature of 50 ° C. Table 2 shows some results obtained with the catalyst [Ru II (bpea) (PPh 3) 2
Cl] Cl covalently anchored to the AlPO4 support, in the hydrogenation of 1-hexene, with different catalyst weights, and different substrate concentrations, obtained by adding different volumes of 1-hexene, for a final methanolic solution volume of 25 mL From these experiences it follows that the most suitable kinetic conditions are obtained for 2.5 g of catalyst and substrate concentrations equal to or greater than 0.7 M.

The results shown in Table 2 have particular that have always been obtained using the same catalyst, as usual in any heterogeneous catalyst, that is to say reusing it, after having recovered it by filtration after use. Operating in these conditions you can check,  comparing the results (a) and (b) in said Table, which after having been reused 27 times, during a month of continued use, the catalyst has been deactivated by 24% use, although here there would be to deduct the losses produced in the manipulation of catalyst, leaks, etc. From here, the catalyst undergoes a rapid deactivation process that greatly reduces important its catalytic activity. However, according to the ultraviolet spectroscopy results of diffuse reflectance, the metal, although practically inactive, remains attached to the support, what which has great economic importance (given its high price) for the ease that this implies for its subsequent recovery. The recovery of the metal, in case it happened to dissolution where reaction products are found, it would be much more hard.

TABLE 2 Reactions carried out at 50ºC and 5 atmospheres of initial hydrogen pressure, with different catalyst weights [Ru II (bpea) (PPh 3) 2 Cl] Cl anchored covalently to AlPO4 support and different concentrations of 1-hexene in methanol

2

Table 2 also shows (c) the value of the speed obtained when 10 mL of wash solution containing the complex [Ru II (PPh 3) 3 Cl 2], which is obtained as a byproduct in the complex synthesis process [Ru II (bpea) (PPh 3) 2 Cl] Cl bound to support AlPO_ {4} (Example 3), for not reacting with the (bpea) anchored to the support. The relative values of these quantities will allow to calculate the amount of Ru anchored in the synthesis process Whenever in 94 mL of wash solution, the entire Ru complex is found in a homogeneous way, to compare the relative velocities of the anchored complex and supernatant, "homogenize" the quantities to compare. Thus, if in 94 mL of wash is the non-anchored complex corresponding to 8 g of prepared catalyst according to Example 3, in 10 mL the part corresponding to 0.851 g. If this solution has a speed of 2.05 µmol / sec, the solution corresponding to 2.5 g (a) would be (2.5x2.05) / 0.851 = 6.022 umol / sec. If we assume that the complex anchored to the support presents similar catalytic activity that the homogeneously dissolved, the speed of the reaction that would get with a 100% complex anchored to the support (or completely dissolved) would be 3,333 + 6,022 = 9,355. Therefore, the amount of immobilized complex in Example 3, will be (3,333 x 100) / 9,355 = 35.6%, which means that in the 8 g solid are supported (35.6 x 0.4) / 100 = 0.14 g, of the 0.4 g of RuCl_ {3} initially used in Example 3. Simple calculations allow to determine that the 8 g of activated support have been retained in 1.75% of RuCl 3 (or 0.83% of Ru) forms covalently. The wash solution containing the complex of Ru-phosphine in a homogeneous way can be recovered by immobilization following the methodology of Example 2.

It has also been carried out, with this same catalyst, a study related to its behavior in the hydrogenation of double bonds, olefinic and carbonyl, in various molecules that are described in the literature scientific as substrates capable of being reduced by Ru, both forming part of organometallic complexes as in metallic form, that is, being part of heterogeneous catalysts. The Results selected in Table 3 allow to verify that with "heterogeneization" of the complexes does not result in important change in its activity and / or selectivity, but unique and exclusively, the possibility of using the catalyst repeated times, and finally recover the noble metal so comparatively easier.

TABLE 3 Reactions carried out with 2.5 g of the catalyst, [Ru II (bpea) (PPh 3) 2 Cl] Cl anchored covalently to support AlPO4, at 50 ° C temperature, at 20 mL of methanolic solution, with different substrates at different concentrations and different initial pressures of hydrogen

3

Claims (35)

1. A process for the chemical fixation of homogeneous catalysts to inorganic solid supports, characterized in that it essentially comprises the following steps:

(to)

subject an inorganic solid support to an activation treatment consisting essentially of the deposition of an amorphous aluminum orthophosphate layer (AlPO4) on said inorganic solid support,

(b)

functionalize the solid support inorganic activated from the previous stage;

(C)

anchor said homogeneous catalyst to support from the previous stage, establishing a link chemical through the functionality introduced on the same.

2. A method according to claim 1, characterized in that in said activation step (a), said amorphous aluminum orthophosphate is deposited in a minimum amount of 20% (w / w). 3. A method according to claim 1, characterized in that step (b) of functionalization essentially comprises the introduction of a group of formula -NH- (CH2) n -NR2 (where n = 2 -6 and R = hydrogen or 2-pyridylmethyl), by means of phosphonido bonds. 4. A process according to claim 3, characterized in that for the introduction of the group of formula NH- (CH2) n -NR2 the activated inorganic support is reacted with an alkylenediamine of formula H2 } N- (CH2) n -
NH2 (where n = 2-6) to obtain said functionalized support where R is hydrogen, proceeding, if desired, following the introduction of the groups R = 2-pyridylmethyl. 5. A method according to claim 1, characterized in that the anchoring step (c) essentially comprises the reaction of the functionalized support, as a ligand, with the metal of a coordination complex or a organometallic complex or a metal salt. A method according to claim 2, characterized in that said inorganic solid support is selected from the group regulated by amorphous aluminum orthophosphate, alumina, silica, activated carbon or sepiolite. 7. A method according to claim 6, characterized in that said inorganic solid support is amorphous aluminum orthophosphate. 8. A method according to claim 6, characterized in that said inorganic solid support is sepiolite. 9. A method according to claim 4, characterized in that the functionalization of the activated inorganic support is carried out with an alkylenediamine of formula H 2 N- (CH 2) n -NH 2 (wherein n = 2-6). 10. A method according to claim 4, characterized in that the functionalization of the activated inorganic support is carried out with ethylenediamine, followed by reaction with picolyl chloride to obtain inorganic solid // AlPO4 // PO3 -NH- (CH 2) 2 -NR 2 (where n = 2 and R = 2-pyridylmethyl). A method according to claim 5, characterized in that the metal-bearing compound in the anchoring stage (c) can be selected from a coordination complex, an organometallic complex or a metal salt, of general formula: L_ {m} B_ {q} MX_ {p} where L is a chiral ligand or not chiral, B is a chiral or non-chiral phosphine type ligand, M is a transition metal, X is a halogen and m, q and p are integers (of 0 a 6) such that the electric charge is compensated 12. A method according to claim 11, characterized in that the ligand L is selected from the group consisting of acetate, hydroxyl, water, chiral anions, amino acids, alkaloids, nicotine. 13. A method according to claim 11, characterized in that ligand B is generally selected from the group consisting of triphenylphosphine, diphenylphosphine, BINAP, PAMP, DiPAMP, DIOP, CHIRAPHOS. 14. A method according to claim 11, characterized in that the metal M is generally selected from the group formed Os, Ir, Pt, Ru, Rh or Pd. 15. A process according to claim 11, characterized in that the halogen X is selected from chlorine, bromine and iodine. 16. A process according to claim 4, characterized in that the functionalization reaction with said alkylenediamine entails the intimate homogenization of the activated supports with the alkylenediamine in the presence of a minimum amount of inert organic solvent against the reaction, followed by solvent removal, Dry solid heating, microwave irradiation and removal of excess reagents. 17. A method according to claim 16, characterized in that said homogenization is carried out a. room temperature under conditions of "incipient humidity" with ethyl ether. 18. A process according to claim 16, characterized in that the heating is carried out at a temperature of 80-120 ° C. 19. A process according to claim 16, characterized in that for the final removal of reagents the reaction product is washed with ethanol and dried. 20. A process according to claim 10, characterized in that the reaction between the functionalized support and the picolyl chloride is carried out under conditions of "incipient humidity" in the presence of a solvent inert to the reaction at a temperature between 60- 100 ° C in the presence of a base, and once the reaction is finished, the product obtained is washed with a suitable solvent and then dried. 21. A process according to claim 20, characterized in that ethanol is used as solvent for homogenization and ethanol is used as solvent for the final washing step. 22. A process according to claims 4 and 11, characterized in that R is hydrogen, and the anchoring reaction is carried out with the compound [Ru II (PPh 3) 3 Cl 2] , obtaining a final product represented by the formula: solid \ inorganic // AlPO_ {4} // PO_ {3} -NH- (CH_ {2}) {n} -NH_ {2} - [Ru II} (PPh 3) 3 Cl] Cl 23. A process according to claims 4 and 11, characterized in that R is hydrogen, and the anchoring reaction is carried out with RuCl 3, in the presence of a reaction inert solvent, of a base, a lithium salt and of triphenylphosphine, obtaining a final product represented by the formula: solid \ inorganic // AlPO_ {4} // PO_ {3} -NH- (CH_ {2}) {n} -NH_ {2} - [Ru II} (PPh 3) 3 Cl] Cl 24. A process according to claims 4 and 11, characterized in that R is hydrogen, and the anchoring reaction is carried out with a compound of the general formula L m B q MX MX where M is selected from the group consisting of Os, Ir, Pt, Ru, Rh or Pd, L is selected from the group consisting of acetate, hydroxyl, water, chiral anions, amino acids, alkaloids, nicotine and B is selected from the group formed per PPh 3 , BINAP, PAMP, DiPAMP, DIOP, CHIRAPHOS; in the presence of a solvent inert to the reaction, obtaining a final product represented by the formula: solid \ inorganic // AlPO_ {4} // PO 3 -NH- (CH 2) n -NH 2 - [ML_ {m} B_ {q} X_ {p-1}] X 25. A process according to claims 4 and 11, characterized in that R is 2-pyridylmethyl, n is 2 and the anchoring reaction is carried out with RuCl 3 in the presence of a reaction inert solvent, of a base, a lithium and triphenylphosphine salt, obtaining a final product represented by the formula: solid \ inorganic // AlPO_ {4} // PO_ {3} -NH- (CH_ {2}) {n} -NR_ {2} - [Ru II} (PPh_3) 2 Cl] Cl 26. A process according to claims 4 and 11, characterized in that R is 2-pyridylmethyl, n is 2 and the anchoring reaction is carried out with a compound of the general formula L m B q MX MX where M is selected from the group consisting of Os, Ir, Pt, Ru, Rh or Pd, L is selected from the group consisting of acetate, hydroxyl, water, chiral anions, amino acids, alkaloids, nicotine and B is selected from the group consisting of PPh_ { 3}, BINAP, PAMP, DiPAMP, DIOP, CHIRAPHOS; in the presence of a solvent inert to the reaction, obtaining a final product represented by the formula: solid \ inorganic // AlPO_ {4} // PO_ {3} -NH- (CH_ {2}) {{}} -NR_ {2} - [ML_ {m} B_ {q} X_ {p-1}] X 27. A process according to claims 4 and 11, characterized in that R is 2-pyridylmethyl, n is 2 and the anchoring reaction is carried out with a RuDIFOSFINE complex, chiral or non-chiral. 28. A process according to claims 4 and 11, characterized in that R is 2-pyridylmethyl, n is 2 and the anchoring reaction is carried out with RuCl 3, in the presence of a reaction inert solvent, of a base , a salt of lithium and 1,2-bis (diphenylphosphine) ethane, obtaining a final product represented by the formula: solid \ inorganic // AlPO_4 // PO_ {3} -NH- (CH_2) n -NR2- [Ru2} (PPh 2 CH 2 CH 2 PPh 2) Cl] Cl 29. A process according to claims 4 and 11, characterized in that R is 2-pyridylmethyl, n is 2 and the anchoring reaction is carried out with RuCl 3, in the presence of a reaction inert solvent, of a base , a lithium salt and BINAP, obtaining a final product represented by the formula: solid \ inorganic // AlPO_4 // PO_ {3} -NH- (CH_2) n -NR2- [Ru2} (BINAP) Cl] Cl 30. A process according to claims 22 to 30, characterized in that the above anchoring reactions are capable of being carried out in one or several steps with or without isolation of intermediate products. 31. A product characterized in that it is the product resulting from the process of any one of the preceding claims 1 to 30, constituted by said solid support coated by the amorphous aluminum orthophosphate layer covalently linked, via a phosphonamide bond, to an amino group of said alkylenediamine whose amino group at the other end is bound to the metal of said complex. 32. Use of the product according to claim 31 as a heterogeneous catalyst. 33. Use according to claim 32 wherein said catalyst is used in phase hydrogenation reactions liquid of alkenes, alkynes and carbonyls to produce the corresponding alkanes, alkenes and alcohols. 34. Use of a product according to claim 31 of particular formula: solid \ inorganic // AlPO_ {4} // PO 3 -NH- (CH 2) n -NR 2 where n = 2 and R = hydrogen or 2-pyridylmethyl, as ion exchange resin useful for recovering different transition metals in ionic form of dilute, or very dilute, solutions in which these are find. 35. Use of a product according to claim 31 of particular formula: solid \ inorganic // AlPO_ {4} // PO 3 -NH- (CH 2) n -NR 2 where n = 2 and R = hydrogen or 2-pyridylmethyl, as active ingredient of drugs able to reduce plasma cholesterol through its ability to fix and remove (by evacuation) bile acids, thus inhibiting its absorption intestinal.