JPS63248437A - Active substance useful as adsorbent and its production - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides metal oxide/hydroxide particles having monolayers of one or more phosphorus-containing organic materials with reactive sites selected above and a useful activity as an adsorbent. Relating to methods of forming substances.

Analytical and industrial sorbents made from organic resins suffer from poor physical strength, poor thermal stability, high cost, bath medium swelling, and low sensitivity. Adsorbents made from gold@oxides such as silica exhibit high - and poor chemical stability. For many applications, sometimes for high pressures and large separation columns, adsorbents with high physical integrity, good chemical stability over high and low conditions, and low cost are needed for a wide range of applications.

Other metal oxides such as alumina have also been used as adsorbents because of alumina's good physical integrity and low cost. Within a range of 4 to 9, the solubility of alumina is extremely low and therefore the material is chemically and physically stable within this range.

However, beyond this range, on the basic or acidic side, alumina becomes soluble in aqueous media and its physical strength and integrity deteriorate rapidly.

Variations of gold@oxide adsorbents such as alumina and aluminosilicates have been proposed. 5tOOkel U.S. Pat. No. 4,506,628 discloses an absorbent animal starch material that utilizes alumina, aluminosilicate, or coal residue as a substrate thoroughly mixed with an in-situ functionalized iterum. Teach. A monomer such as vinylphosphonic acid, along with a redox catalyst, is mixed with a flexible dough formed from alumina and water and extruded into pellets that harden as the polymer polymerizes.

Modified alumina has also been conveniently used to form catalysts.

Johnson et al., U.S. Pat. Nos. 4,202,798 and 4,251,350, disclose contacting alumina with a phosphorus-containing acid, such as phenylphosphonic acid, and then calcining the phosphorus-containing water-fed alumina. The formation of a hydrocarbon hydroprocessing catalyst is described. The calcined alumina is then treated with a small amount of a metal-containing compound and calcined again to form a catalyst product.

Additionally, U.S. Pat. No. 3,013,904 for Cup51r7
No. 1 describes a substrate having an organic polymer containing pentavalent phosphorus attached thereto. A phosphorus-functionalized polymer coating is applied over a positively charged colloidal metal oxide coating applied to a negatively charged substrate. The thickness of one combined colloidal modification layer on the substrate is less than 100 millimicrons.

Venables et al., U.S. Pat. No. 4,308,079, discloses that nitrilotris (methylene ) describes the treatment of the aluminum oxide surface of an aluminum substrate with a monolayer of an aminophosphonate compound such as triphosphonic acid. The presence of hydroxides is said to interfere with the formation of sufficient bonds between the adhesive and oxides, and the phosphonate treatment does not interfere with the bonding of the adhesives to the oxides (the oxides to the hydroxides). It is said to prevent conversion.

In accordance with the present invention there is provided an active material comprising metal oxide/hydroxide particles having a monolayer of one or more types of phosphorus-containing organic molecules chemically bound to reactive positions on their surface. This organic molecule is oriented from the surface of the metal oxide/hydroxide particle with a phosphorus-containing group capable of forming chemical bonds with the reactive positions of the metal oxide/hydroxide particle and with the active component or position of the molecule. consisting of carbon-containing groups or positions that can function as

In accordance with one embodiment of the invention, the active material comprises metal oxide/hydroxide particles having substantially monolayers of phosphorus-containing organic material chemically bonded thereto, wherein the organic molecules having phosphorus-containing groups are It further contains carbon-containing groups oriented away from the surface of the metal oxide/hydroxide particles and capable of functioning as the active component of the molecule. The active material is conveniently suited as an adsorbent, which is stable over a large range, in some cases from 1 to 14, or from 2 to 11, and is useful as a support material for metal oxides/hydroxides. At least some of them are insoluble in aqueous media.

This active substance is also useful for: Analytical and preparative scale chromadogs: Seven-layer supports: Ion exchange media: Biological materials, such as biomass, yeast, proteins, microorganisms, preparations, etc. Cassirer for pharmaceuticals and vaccines containing time-release drugs: Stabilization of inorganic membranes useful in high and low temperatures: Coatings for piezoelectric crystals: Spacer molecules to hold metal oxide particles apart ; coatings for inorganic fillers and flame retardants in polymers;
Coatings to inhibit cation or anion adsorption (W CPI, F-adsorption on alumina): Formation of hydrophobic surfaces on metal oxides to adjust wetting and dispersion properties in fluid media: Surface charge in fluid media Controlling: Facilitators for adhesive bonding of metals, ceramics and polymers: Immobilizing optically active molecules (chirality) for selective adsorption of optically active compounds (d or! isomers) Coupler for: Surface modification for biological implantation (e.g. passivation surfaces of bones, joints, teeth): Additives to pharmaceutical products (fillers, colorants, toothpaste fragrances, creams): Electrical insulation Improved bonding between body and metal conductor (reduced delamination from weathering)
Adjusting the abrasion properties of metal oxide powders: complexing agent for catalytically active metals for improved metal dispersion, stain resistance and abrasion resistance for niblastic, concrete or soft metal wear surfaces; What happens: Adsorption of water (
Selection of toxic liquids or gases Last fall N: Polymers and materials fjr
:y# Couplers for coloring; protective coatings for natural products such as wood, straw and stone to increase surface hardness, stain resistance and color fastness; photon by increased adsorption and/or light scattering Coatings that increase the efficiency of radiation: pharmaceuticals, treated textiles and wood (e.g. filamentous fungi,
Coatings with antibacterial properties for treated wood products to prevent the formation of mold and rot: flocculants for colloidal dispersion; metal chelating agents: as additives and extenders for polishing and as wetting agents. yes. Additionally, the active substances are also useful in diagnostic test devices or methods or therapeutic devices or methods. This active substance can be applied to membranes such as inorganic membranes and used for reverse osmosis dialysis and ultrafiltration.

The use of the term "active agent" means that it can be attached to a metal oxide/hydroxide support, preferably at the end of the molecule, having a phosphorus-functional group and preferably at the opposite end of the molecule, its an organic compound containing a monomer, oligomer or short chain polymer having one or more positions on which it can be used for coupling, bonding or adsorption to atoms, ions or other molecules If a molecule is to be defined, for example when this active substance acts as an adsorbent, this active substance has available positions on the molecule onto which the substance to be adsorbed will be attracted.

The use of the term ``metal oxide/hydroxide'' here is intended to limit a broad spectrum of oxides, from including only trace hydroxides, such as aluminum oxide in activated or calcined form. (alumina) in a hydrated form containing mainly hydroxides, e.g. However, for some applications, the dehydrated or activated form of the metal oxide/hydroxide is preferred due to the higher surface area of the particles.

For example, when aluminum oxides/hydroxides are used, the hydrated form is preferred; for example, when a large external surface area is desired, gibbsite, /s4 yerite or boehmite are preferred; metal oxides/hydroxides are highly Activated alumina is preferred when it is desired to have internal surface area.

As understood herein, metal oxides/hydroxides suitable for use in the present invention typically require hydroxyl groups on their surface for purposes of providing bonding sites for phosphorus-containing organic materials. . For example, when the particulate material is alumina, the hydroxyl groups on the surface of the alumina can be combined with one or more phosphorus-containing groups of the organic molecule, i.e. with -POOH acid groups of phosphonic or phosphinic acids, or with phosphoric acid monoesters or phosphoric acid groups. Reacts with -PO(OH) groups of acid diesters or organic phosphoramidates or organic thiophosphates. When using organic solvents, especially if the solvent is immiscible with water, for the purpose of forming chemical bonds with phosphonic or phosphinic acid groups or with phosphoric acid groups of phosphoric acid mono- or diesters. A monolayer of hydroxyl groups is provided on the alumina particles. If more than a single layer of hydroxyl units is present on the alumina surface, for example as a result of water, it has been observed that this extra water f- acts to inhibit the reaction. Good morning. It is therefore preferable to have a monolayer of at most 10,000 hydroxyl units, although less than a complete surface layer of hydroxyl units can be present on the metal oxide and this does not inhibit the reactivity.

Metal oxides/hydroxides that can be used as support particles for reaction with phosphorus-containing organic substances are Group IB.

It A % n Bs m A % EV A s
v As III B s tv B %VB%VIB
Enriched with any metal capable of forming oxides/hydroxides selected from the group consisting of % B and B, and combinations thereof. For example, aluminum, magnesium, titanium),
Oxides/hydroxides of zorconium, iron, silicon, chromium, zinc, vanadium and combinations thereof can be used. Also, cores or centers of iron oxide/hydroxide or other paramagnetic or diamagnetic materials can be used with coatings of metal compounds to take advantage of the magnetic properties of iron oxide/hydroxide as adsorbents. The use of the term ``metal'' refers only to the customary metals, and also includes substances sometimes referred to as metalloids, such as Sl, Sθ, B, Ali!, and Te, and the rest referred to as non-metals in the periodic table. Furthermore, oxides/hydroxides of the ranknyl series and oxides/hydroxides of thorium and uranium in the actinide series can be used as support particles. .

While the present invention is primarily directed to the use of metal oxide/hydroxide particles as support materials for reaction with phosphorus-containing organic molecules to form active substances, this Alternatively other metal compounds such as metal silicates, oxalates, phosphates, sulfates, carbonates, apatites, hydrotalcites, zeolites, kaoli), clays and chromates, and combinations or It is within the scope of this invention that combinations of any of these materials with suitable metal oxide/hydroxide support materials can be used.

Regarding the metal oxides/hydroxides used in the present invention, these may be provided in particulate form for certain applications. When the application is as an adsorbent, particle sizes range from as low as 50 angstroms, providing large external surfaces, to 12 millimeters for large reactors. When the adsorbent base is alumina, the particle size is 1 to 200 microns. Other applications, such as flocculation), flame retardants in polymers, and heterogeneous catalysts require different particle sizes. However, typically for adsorbents, the particle size is greater than 1 micron. When the metal oxide/hydroxide particles include aluminum oxide/hydroxide (alumina), a typical particle size distribution is 1.3-6.7-12.10-1
8.18-32.32-63 microns and 50-200 microns.

Regarding the particle size morphology of the metal oxides/hydroxides useful in the present invention, for example for metal oxides/hydroxides such as alumina or iron oxides for the purposes of the present invention, these are
Preferably, the pore size is between 0 angstroms and 10 microns. Furthermore, this particle has a particle size of 0.1 to 1.5 m/
It is preferred to have a pore volume of &. Regarding purity, the level of impurities should be kept to a minimum depending on the end use.

However, for example, the metal oxide/hydroxide relative to the adsorbent should be at a purity level of 80% or higher, preferably 95% or higher. The surface area of the particles is preferably high with typical surface areas, e.g. in the range of 0.10 to 600 m"/,9 for alumina and 1000 m"/.9 for other metal oxides/hydroxides such as silica.
/# up to.

To produce an active substance containing a metal oxide/hydroxide reacted with one or more types of phosphorus-containing organic molecules,
A metal oxide/hydroxide such as alumina is combined with a phosphonic or phosphinic acid or a phosphoric acid monoester or diester in an aqueous medium of at least about 0.0001 to 0.1
at a temperature of about 25 to about 90°C, preferably about 50°C, using an initial acid concentration of at least 0.1 to 20 molar.
thicker than time (no, and preferably at least about 0
．． Allow to react for 5 to about 4 hours. In some cases,
Higher concentrations are desirable. When the medium is non-aqueous,
The temperature range can be greatly increased. For example, it can range from 5°C or less to 200°C or sometimes higher depending on the liquid medium.

In the present invention, the single layer weight ranges from about 0.01 to 90 weight units based on the total amount of coated metal oxide, and preferably the single layer is approximately 4 to 50 weight units, typically Generally, it ranges from 5 to 20 weights. When the metal oxide/hydroxide particles are very small, this monolayer weight is equal to or greater than the weight of the particles. This application must be carefully regulated in order to ensure that the phosphonate organic monolayer binds to the metal oxide particles. That is, a monolayer is obtained by adjusting the viscosity of the aqueous medium, the time of exposure to the medium, the concentration of phosphorus-containing organic material in the medium, or the 11 degrees of hydroxyl units on the metal oxide particles. Furthermore, in order to ensure a monolayer, after formation of the active substance it is treated with an organic solvent, a basic or acidic solution or a combination thereof. - An example is a NaHOO3/Na2CO3 wash solution with about 10 - to remove weakly adsorbed molecules on the particles. This ensures that all remaining molecules bind to the hydroxyl groups on the metal oxide/hydroxide surface and do not bind to each other, thus ensuring the formation of the desired monolayer that is stable over a wide range of temperatures.

The formula for phosphonic acids useful in the practice of this invention is RPO (
OH) 2, while phosphinic acid is RR' POC
0H), where R' may be hydrogen and R and y are each a molecule containing 1-30, preferably 5-60 carbons, such as an alkyl group. Other examples of R- and/or y-enriched groups are long- and short-chain aliphatic hydrocarbons, aromatic hydrocarbons, carboxylic acids, aldehydes, keto), amides, thioamides, lactams, anili), pyridi), piperidi), anhydrides, carbohydrates, thiocyanates, esters, lacto), ethers, alke), alkyl), alcohols, nitriles, oximes, organosilico), sulfur-rich organic compounds, urea, thiourea, perfluor 2i cr It is enriched in polypropylene molecules, perchloroorganic molecules, perbromoorganic molecules, and combinations of these groups.

The formula & (
RO)PO(OH)2 (phosphoric acid monoester or monophosphate), -panic phosphoric acid diester (RO)
)(R'O)PO(OH), R and R'
is an organic group containing 1 to 30 carbon atoms, preferably 5-
A 30 carbon molecule, such as an alkyl group.

The other 91 groups containing R and/or yyk are long-chain and short-chain aliphatic hydrocarbons, aromatic hydrocarbons, carbanoic acids, aldehydes, keto), amide, thioamide, imide, lactam, anili) , bilici), piperidi), anhydrides, carbohydrates, thiocyanates, esters, lacto), ethers, alke), alkyl), alcohols, nitriles, oximes, organosilico), sulfur-containing organic compounds, urea, thiourea, perfluoroorganic Enriched with molecules, perfluoro-organic molecules, perdermo-organic molecules and combinations of these groups.

Phosphorus-containing organic molecules such as those listed above also include inorganic groups substituted thereon, such as halobi), nitrates, phosphates, phosphinates, phosphinites, phosphonates, quaternary ammonium salts. Although the free end of the organic group preferably extends away from the surface of the metal surface particle, it is within the scope of the invention to provide one or more functional groups on the free end of the molecule. Functional groups allow reactive substances (including phosphorus-containing organic substances attached to metal oxide/hydroxide surfaces) to react, attract, couple, and bond with other atoms, ions, and/or molecules. It can be defined as a group on a molecule that makes An intermediate group can be defined as a group on a molecule that allows the substitution or addition of groups or compounds to the R or R' groups after the monolayer has been formed on the oxide/hydroxide particles. The same as the intermediate group,
(enriched with J, Br, ON, etc.) This intermediate group is a group that is not compatible or destroyed during the formation of the monolayer, or allows for the addition of radicals. or the addition of functional groups to the ends of R'.By adding specific functional groups, either organic or inorganic, to the R and R' groups of the phosphonic or phosphinic acids, a wide variety of Adsorbent selectivity and performance are provided.

The functional groups added to the free end or included in the circle include cation exchange functional groups and anion exchange functional groups, such as -H8
03, -N(OH3)3CJ, -COONa, -NH
2 and -(IIN.-HEI03 functional group can be selected from aqueous medium cu +2.1pe +5!, OO+2
, Od+2, Ca+2, B r+2, Hg +2, p
Allows removal of cations such as b+2, Ba +2 and Be +2. Functional group, -0H2N''(OH3)3C
J is HSO, -10:LO3"', No3-1NO2-
Removal of anions such as 1HPO4-, ioate, and citric acid. Other examples of functional groups that can be terminated at the free end of a phosphonate-linked hydrocarbon are nicarpoxyl groups, such as carboxymethyl groups, glucose groups, enriched with:
Monoclonal antibody, cyano group (-0=N), phenyl group, diphenyl group, tert-butyl group, sulfonic group,
benzylsulfonic groups, protein groups such as protein A (staphylococcal protein A), protein G, immunoglobulins and their binders, pharmaceutical compounds, yeast, microorganisms, whole cells, enzyme groups, dye molecules, chelated gold groups, including tag molecules and combinations of these groups. Additionally, it should be noted that the carbon group can be a saturated or unsaturated carbon chain.

It will be noted that the R or R' groups are always monomeric or oligomeric. Preferably, this oligomer is 200
It has a molecular weight of 0 or less. Here, simply using the body is a chemical compound that can undergo polymerization vlJfj! : Means to become rich.

By oligomer is meant a polymer or polymer intermediate containing relatively cheap structural units, ie, a polymer containing 2-4 monomers.

Without wishing to be bound by any particular theory of bonding, it is believed that when metal oxide/hydroxide particles, such as alumina, are brought into contact with a phosphoric acid monoester or phosphoric acid zoester, there is reaction or adsorption of the acid on the alumina. occurs, where in each molecule the aluminum and phosphorus atoms appear to be explicitly bonded together via an oxygen atom as shown in the formula: P
=0 ToR-0-ThOI(+-Al-0-n- →-foot-0-
Al-+H,0OH Phosphoric acid Irrigation+ Monoester Alumina Product 10 Water R' 彊 ■ OH0 R'-0-P=0 Diester Alumina Note: Aluminum ions may or may not have coordination vacancies on or near the surface. are also octahedrally or tetrahedrally coordinated cations (externally or inside the pore structure).

Also, while not wishing to be bound to any particular theory of bonding, when metal oxide/hydroxide particles, e.g. alumina, are brought into contact with a phosphonic or phosphinic acid,
A reaction or adsorption of the acid occurs on the alumina, where the aluminum and phosphorus atoms in each molecule are believed to be explicitly bonded together via an oxygen atom as shown in the following formula: R'-P=0 R'- P=0: Aluminum ions are cations that have coordination vacancies on or near the surface and are octahedrally or tetrahedrally coordinated cations (with external and internal pore structures). ).

Thus, if all of the exposed hydroxyl groups on the surface of alumina can react with phosphonic or phosphinic acid groups or with phosphorus monoester or diester groups, it is possible that the surface chemistry of the reacted alumina will change. This becomes clear using the model proposed above. Furthermore, the type of organic group attached to the above groups can be tailored to obtain a particular type of affinity to impart selectivity to the adsorption properties of the product. For example, when using alumina treated with phosphonic acid or phosphinic acid having an octadecyl R group, or when using alumina treated with a phosphoric acid monoester or phosphoric acid diester having a dodecyl R group, the following type is used. Under chromatographic conditions, for example, methyl benzoate, 7enethole and 0-xylene can be selectively adsorbed onto the reactive substances according to the invention, such that a selectivity of cI is obtained.

The chemical bonding of phosphonic or phosphinic acids, or phosphoric acid monoesters or phosphoric diesters to metal oxide/hydroxide particles, e.g. alumina, is shown in Figure 8, where the center is an alumina particle with surface 50'lf: Na Omote Wa Ding. The carbon-containing molecules are chemically bonded to the surface 50 at one end by a phosphorus-oxygen-metal bond. As understood herein,
Preferably, the other or free end of the carbon-containing molecule extends away from the surface of the particle as shown in FIG. Additionally, phosphonic or phosphinic acids, or phosphoric acid monoesters or phosphoric acids are added to the metal oxide/hydroxide support to obtain a monolayer bonded to the metal oxide/hydroxide particles as shown in FIG. It is important to control the application or attachment of the acid diester.

By "one monolayer" or "one monolayer" is meant that 90% and preferably 98% of the phosphonic or phosphinic acid is bound to the metal oxide/hydroxide particle as a single layer of molecules. Thus, the R or R' groups bond to each other to form a weakly adsorbed multilayer, which then rotates away from the surface of the metal oxide/hydroxide particle and separates the particles from bonding to this surface. Hydroxyl unit h, immediately? )-po
The application must be adjusted so as to avoid defeating the purpose of the invention by providing an oH unit, for example when used as an adsorbent. The thickness of this phosphorus-rich bonded organic monolayer is in the range of 10-5000 angstroms and preferably 20-500 angstroms.

As mentioned above, while it is desirable to avoid organic polymers with repeating phosphorus-containing groups whose chains can be attached to the metal oxide particle surface, oritemers with a single phosphorus-binding group are preferably utilized. This single functional group allows the oligomer to have a free end that extends away from the metal oxide particle surface.

Additionally, the monomers or oligomers that make up the monolayer have reactive sites, which can allow cross-linking to polymerize the monomers or oligomers already bound to the surface of the metal oxide particles. .

In the present invention, especially when the end use is as a N absorption agent,
It is preferred that the corrugated body or oligomer used has at least 5 carbon chains. This chain can have from 20 to 30 or more carbons as mentioned above. Preferably longer chains are used for initial bonding or loading of the metal oxide particles with the phosphorus-containing carbon material. However, because
Gold P! The pores and fissures present on the tetraoxide particles are due to the
Particularly those with large surface areas, often all surface hydroxyl units do not react because the long-chain phosphorus-containing organic materials cannot penetrate or diffuse through the pores and fissures into the eye. Therefore, short chain monomers or oligomers, such as 6 or fewer carbon molecules per chain, can be used to inactivate or block the remaining reactive sites. In this way, all reaction sites are capped or blocked.

Short chain monomers can be used to cap the reaction sites. For example, alumina treated with a high molecular weight phosphonic acid or phosphinic acid, such as n-heptadecylphosphonic acid, can be further treated with a lower molecular weight phosphonic acid, such as methylphosphonic acid, to treat remaining unreacted alumina surface areas. For example, alumina treated with a polymeric t-phosphoric acid monoester or phosphoric acid diester, such as n-dodecyl phosphoric acid, may be further treated with a lower molecular weight phosphoric acid, such as methyl phosphoric acid, or a mixture of methyl phosphoric acid and dimethyl phosphoric acid. The remaining unreacted alumina surface area can be treated.

Another embodiment of the invention relates to coupled, eg, affinity or reverse phase chromatography column packing materials.

More particularly, the present invention involves reacting metal oxides/hydroxides with phosphoric acid to form a monolayer thereon, thereby providing a reversed phase chromatography packing material with good monostability as well as high efficiency. Regarding things.

Chromatographic packing materials made from resins suffer from poor physical strength, poor thermal stability, high cost, solvent swelling, and low capacity.

Chromatographic packing materials made from gold phosphorous oxides, such as silica, exhibit high- and poor chemical stability. For many applications, especially for reversed-phase chromatography, high physical integrity, good chemical stability over high and low Pk'i, specific narrow surface functionality, good thermal stability and low cost A la magnification filling material is required.

In another embodiment of the foregoing, the non-polar portion(s) of the molecule is oriented away from the surface of the metal oxide/hydroxide particle for interaction with the organic material passing through the chromatography column. A chromatographic packing material is provided comprising gold N oxide/hydroxide particles having a monolayer of phosphonic acid chemically bonded to reactive sites on the surface.

In accordance with another embodiment of the invention described above, the chromatographic packing material is enriched with metal oxide/hydroxide particles having substantially monolayers of one or more phosphonic acids chemically bound thereto. .

Reverse phase chromatography means that the adsorbent is less polar than the elution solvent, and in normal phase chromatography the adsorbent is more polar than the elution solvent. That is, in reverse phase chromatography, more non-polar sample components interact more with the relatively non-polar column backing and therefore elute later than polar sample components. Typical mobile phases for reversed phase chromatography are aqueous buffers, water, methanol, acetonitrile, tetrahydrofura), and mixtures of these organic solvents with water or buffers.

A metal oxide/hydroxide, such as alumina, is combined with at least one phosphonic acid in an aqueous medium to produce a chromatographic packing material rich in metal oxides/hydroxides reacted with one or more phosphonic acids. Approximately 0.0001 to approximately 0
．． from about 25 to about 9 using initial acid concentrations up to 1 molar.
At a temperature of up to 0°C, preferably about 25°C, at least 0.
no more than 1 to 20 hours, and preferably about 0
．． Allow to react for 5 to about 4 hours. In some cases, a higher degree is desirable. This temperature range can be greatly expanded when the medium is non-aqueous. For example, they range from 5° C. or less to 200° C. and sometimes higher depending on the particular liquid medium.

For the purpose of ensuring that a monolayer of phosphonic acid or metal modifier is bound to the particles, care should be taken in its application. Thus, for example, a monolayer is obtained by adjusting the viscosity of the medium, the time of incubation in the medium, the concentration of phosphorus-bonded hydroxyl units in the medium, or the concentration of hydroxyl units on the metal oxide particles.

120- to reversed phase chromatography packing material used as column packing material for reversed phase chromatography
100.000:N/'x Trom, preferably about 40-1000 Angstroms pore diameter size, about 0.
1-2m/#, preferably about 0.5-1.5 rttt
/fJ, 9'lJ, tif 0.3 Kara o, a
m/, about 0.5-300 microns with 9 tv hole volume)
, preferably a metal oxide/hydroxide, preferably having a particle size range of about 1-80 microns, preferably an aluminum oxide/
Rich in hydroxides.

This reversed phase chromatography packing material was further bonded as a monolayer at reactive sites on the surface of the aluminum oxide/vesicle support material at 1-75 quadrillion t% (based on the total amount of packing material). [calculated based on], at, <=4-5U, and typically contains 5-20% of one or more phosphonic acids.

The phosphonic acid bound to the support material is preferably from 2 to 97! t%, preferably 25-95! t% (calculated based on the total amount of phosphonic acid)
(1) Formula R' P.O.
(OH)2, where R' is a 1 to 4 carbon saturated or unsaturated aliphatic hydrocarbon.

Preferably R' is a single carbon group, i.e. treated with a long chain phosphonic acid and then reacted with the aluminum oxide/hydroxide surface to react with the remaining hydroxyl groups on the aluminum oxide/hydroxide surface. Methylphosphonic acid provides good peak symmetry for the material being passed through the column for analysis.

It will be noted that the R group is always monomeric or oligomeric. Preferably, the oligomer has a molecule t less than or equal to 20 (JO), where the term monomer is meant to include compounds capable of compounding. Polymer or complex intermediates, i.e. 2-
It means a polymer containing 4 monomers.

Without wishing to be bound by any theory of bonding, it is believed that metal oxide/hydroxide particles, such as alumina, are contacted with a phosphonic acid (containing either long-chain or short-chain carbon groups as discussed above). A reaction or adsorption of the acid occurs on the alumina when the aluminum and phosphorus atoms in each molecule are introduced into Either the long-chain R group or the short-chain R' group appears to be explicitly bonded together via an oxygen atom as shown in HO-P=O+ -Al-0- AI--4-A 〇-A nee + H2OOH Using the model proposed above, if all of the exposed hydroxyl groups on the surface of alumina can react with phosphonic acid groups, then the amount of reacted alumina It can be seen that the surface chemistry will change. When using alumina treated with phosphonic acid having octadecyl R groups, under chromatographic conditions, e.g. Can be selectively adsorbed to filling materials.

The available surface area, both outside and inside the pores, varies slightly depending on the relationship between the pore size of the aluminum oxide/hydroxide support material and the length of the R group of the phosphonic acid. If the pore size is small relative to the size of the R group of the phosphonic acid molecule, the phosphonic acid will not be able to enter or enter the pores, thereby making it available for interaction with the organic material passing through the chromatography column. The effective area obtained changes.

The pores and fissures present on the metal oxide/water particles have a particularly large surface area due to their size, and often the surface hydroxyl groups on the surface do not react, the reason being that long chain phosphorus This is because the organic substances contained cannot reach or diffuse into the pores and fissures. Thus, to inactivate or block the remaining reaction sites, short chain monomers or oligo-:1m'ff-, e.g. R'PO(OH)2phosphones containing 1-4 carbon atoms per chain, The acid is used in a second treatment or reaction. In this way, all reaction sites are capped or blocked. That is, short chain monomers can be used to cap the reactive positions.

For example, alumina treated with a high molecular weight phosphonic acid, e.g., n-heptadecylphosphonic acid, corresponding to the formula RPO(OH) 2 may be further treated with a lower molecular weight phosphonic acid, e.g., methylphosphonic acid to remove any remaining unreacted alumina surface. area can be treated.

In this regard, it is not the short-chain R' groups that interact in principle with each organic substance passed through the column to provide individual peaks that identify specific organic substances passing through the column at different rates of elution. , is a long chain hydrocarbon R group. The primary function of short-chain R' groups is that the non-polar or polar groups of the organic material passing through the column interact with the exposed hydroxyl groups on the support material (from the polarized ends of the organic molecules passing through the column). rather] to react with the remaining hydroxyl groups on the aluminum oxide/hydroxide support material to interact with the non-polar packing material, thus creating a true reverse phase filter through the chromatography column. (so that the short-chain phosphonic acid has sufficient placement to bind to all remaining reactive hydroxyl positions on the support surface after initial treatment of the long-chain phosphonic acid or acids. must be reacted with the support surface.

After formation of the filler material, this material is treated with an organic solvent or a basic or acidic bath solution, or a combination thereof, such as about p) 11
The weakly adsorbed molecules on the particles can be removed by treatment with a NaHCO3/Na2003 wash bath solution with 0. This ensures that all of the remaining molecules bond to the hydroxyl groups on the metal/hydroxide surface rather than to each other, thus forming the desired monolayer that is stable over a wide range of 7g! :! keep

The resulting reverse phase chromatography packing material is stable in the range of 1-14 and has good stability in the range of 2-12 while still maintaining high efficiency of separation. Typically, 1
A reverse phase packing material based on alumina particles of approximately 10 microns in diameter with an initial surface area of 50 m”/y is
, ooo yields a chromatographic support with a high N number of 25,000 or more (N being the theoretical plate number).

The following columns are presented to further illustrate the practice of the invention.

Row 1 High purity bayerite and gamma alumina were used as supports. Nitrogen BIT for bayerite and gamma respectively
The surface areas were 19 and 65 m''/#.

Both bayerite and gamma alumina with an average particle size of about 2 i Kron were dried in a drying oven at 110 °C and 10
A large amount of the 11K family was weighed into a glass sample bottle.

0.1, 0.01.0 of phenylphosphonic acid formed by diluting 0.1 mole of phenylphosphonic acid with deionized and distilled water into each of four glass bottles enriched with 10I samples of gamma alumina. .001, and o, o
100 molar solution was added.

0.01.0.001 and 0.01. The molar concentration of OC301 produced a monolayer but did not cover all of the available surface area on the particles. A molar concentration of 0.1 was sufficient to provide a monolayer over most of the surface area of the particles. If the amount is higher than 0.1 mol, multi-layering will occur, which is undesirable. Five 10y samples of gamma alumina were charged with 100y of deionized and distilled water. Five additional samples were similarly prepared using bayerite sample 10& instead of gamma alumina. The 10 samples were shaken and allowed to age for 24 hours. The contents of each sample vessel were then vacuum filtered through Whatman 42 filter paper. This surface-modified alumina was placed in a clean glass bottle and dried in a drying oven at 110°C. The phosphorus content of each sample was determined by direct current plasma mass spectroscopy.

The results are shown in Table 1 and plotted on the graph of FIG. It can be seen that there is a significant increase in the amount of phosphorus present on the surface of beyerite and gamma alumina aged in a 1 molar solution of c7 enylphosulfosulfonic acid compared to the amount of lower concentrations. Gamma alumina's higher phosphorus content is due to its higher surface area.

Table 1 1 Bayerite o, oooo o
,o.

2 bayerite 0.0001 0.
016 bayerite 0.001
0.014 bayerite 0.01
0.065 bayerite 0.1
0.616 gamma o,
ooooo o, o.

7 Gamma 0.0001 0.
018 Gamma 0.001
0.049 Gamma U, 01
0.2910 Gamma 0.1
1.85 Example 2 Another group of 10 samples of gamma and bayerite was prepared and each sample was treated with 0.1 mol phenylphosphonic acid 10
0- was added. Each sample bottle was covered, shaken and allowed to age for the scheduled time, followed by filtration.
After drying, the phosphorus content on the alumina samples was determined in terms of contact time between each alumina sample and phenylphosphonic acid using measurements similar to those previously described in Example 1. These results are displayed in Table 2 and illustrated in the graph of FIG.

Filtrates for alumina samples aged for various times were analyzed for phosphorus content. The concentration of phosphorus in beyerite and gamma alumina filtrates aged for the length of time is plotted in FIG. The changes in each solution for gamma and bayerite samples aged for 24 hours were monitored and plotted in Figure 6 for the change in -ft vs. time to monitor the amount of phenylphosphonic version chemically bonded onto the alumina. I will show you another method. It can be seen that the gamma alumina containing solution shows a sharp increase between 0 and 60 minutes, then a gradual increase until 120 minutes, at which point it begins to decrease slightly.

The DO of the solution containing the bayerite alumina sample shows a linear increase in DO from 0 to about 150 minutes and then decreases slightly. Alumina other than bayerite and gamma alumina, such as evesite, boehmite, eta, chi,
Rho, delta, kappa and alpha alumina can be used as supports.

Table 2 1 Bayerite 2 0
．． 122 bayerite 4
0.116 bayerite 8
0.124 bayerite
16 0.125 bayerite
32 0.116 Bayerite 64 0.137 Bayerite 128 0.128
bayerite 256 0.389
Bayerite 1440 1.
3110 Gamma 2
0.7211 Gamma
4 0.6212 Gamma
8 0.6513 Gamma
16 0.6714 Gamma 32 0.6215
Gamma 64 0.
6316 Gamma 128
0.6517 Gamma 25
6 0.8018 Gamma
1440 1.56 Example 3 To further illustrate the practice of the invention, 0.1.0.
Each of the filtered and dried alumina samples from Example 1 was contacted with 0.01 and 0.0001 mol phenylphosphonic acid. Distilled to l', washed 6 times with deionized water and filtered. The filtered and dried 6y gamma alumina samples from Example 2 were similarly washed by contacting with 0.1 M phenylphosphonic acid for 8.64 and 1440 minutes each.

All washed samples were then placed into clean glass bottles and dried in a 110°C drying oven. Gamma alumina samples contacted with 0.61 molar 7-alephosphonic acid were not wettable. These were also unaffected by washing.

The results are shown in Figures 4 and 5, respectively, where the results from the washed samples are superimposed on the respective solid gamma curves for the unwashed samples, which correspond to the gamma curves published in Figures 1 and 2. Plot with a dotted line.

It will be noted that the phosphorus residue remaining on the treated alumina after washing can be quite comparable to the unwashed sample.

Example 4 To illustrate the double treatment of alumina with one or more types of phosphonic or phosphinic acids, 120 t of inzolopanol at 45°C! 3.8454 per ton! A solution of 0.1 molar n-heptadecylphosphonic acid was prepared by dissolving i'. activated 7-12 micron aluminium 30
& was weighed into this solution, which was then shaken to mix and placed in an ultrasonic bath for 15 minutes. The mixture was filtered through Whatma+6 filter paper. The alumina was washed with 6 ml of inzolopanol and dried in an oven at 110°C. The unreacted sites on the alumina surface were then capped with methylphosphonine. Improper tool 120ff17 at 45℃! Methylphosphonic acid 1.152
A solution of 0.1 molar methylphosphonic acid was prepared by curing 4μ. Add 270% dry, n-heptadecylphosphonic acid loaded alumina to this, shake to mix, and place in an ultrasonic bath for 15 minutes. The alumina was filtered again through arrows, washed and dried at 110°C.

A separate alumina sample was then contacted under the same conditions with a 0.6 molar solution of n-heptadecylphosphonic acid dissolved in inzolopanol, and the arrow was capped with a 0.1 molar solution of methylphosphonic acid as described above.

Both samples were analyzed at 912 spectra with 4 tx-” resolution.
Eight scans were analyzed on an IBM Instrument R-98 Fourier Transform Infrared Spectrometer. This spectrum was plotted using the KBr spectrum as a standard. The bands chosen for the n-heptadecylphosphonic acid calibration curve were the 2928 cm asymmetric stretch band and the 1470 Cwt-" bending band. 1470 cm
The band at −1 was chosen as the analysis wavelength because the value for the 70° standard deviation is 10 times less than that for the band at 2928° −1. At this wavelength,
The 1% of each type of n-heptadecylphosphonic acid loaded by treating alumina with 0.1 molar and 0.6 molar solutions were 6.88 and 24.85 wt. 1%, respectively.

Row 5 A reverse phase chromatography packing material was prepared according to the invention by reacting an aluminum oxide/hydroxide support material with 0.1 mole of long chain phosphonic acid for 1 hour at a temperature of 120°C. The support material was then reacted with 1 molar methylphosphonic acid at 120° C. for 1 hour to cap the remaining reactive heroxyl units on the support material. The support material has a particle size range of about 7-12S Kron.
The aluminum oxide/hydroxide'ft had a pore diameter range of about 20 to 100 angstroms and a pore volume of about 0.2 to 1.0 mm/l.

The long chain phosphonic acid is octadecyl acid and the ratio of the two phosphonic positions is 7% by weight octadecyl acid and 4% thimethyl phosphonic acid, and the total weight of the phosphonic acid on the aluminum oxide/hydroxide support is 7% by weight. The yield ratio was 11 weight kilns. This reverse phase Kukomatog 2 fee filling material about 5
25 CI for g! 4.6 mm to the height of L D
, packed into the column to provide a total volume of about 4 to 5 fnt.

p-nitroaniline 0.2#, methyl benzoate 0.2g, phenetol 0 dissolved in methanol 10100O
．． A test mixture consisting of 2y and 0-xylene 0.2y was prepared. The test mixture was injected into the column at various times and eluted from the column with a solvent system of 40% water, 30% methanol and 60% acetonitrile at a flow rate of 1.25 m/min. - in the water part of the solvent system is sodium carbonate /
After increasing the pH to 10 with sodium hydroxide buffer and running for 2 hours, the efficiency was N=19.000, indicating that the packed material kept its stability and high efficiency for a long time of use. The same solvent system with - adjusted to 12 via the addition of extra sodium hydroxide was added to 4 more
Passed through the same column for 8 hours and efficient N=25
．． 000, which was high - indicating high efficiency and good stability of the material. Chromatographic measurements showing sharp kink for each of the four substances for 2 and 48 hours at PH 10 and over 48 hours at PH 12 are shown in Figures 9A-9C, respectively.

The foregoing thus shows that the present invention provides an improved reverse phase chromatography packing material that exhibits good stability over a wide range with good separation efficiency.

The above example also shows a concentration of about 0.0001 to 0.1 molar until a sufficient amount of the phosphorus-containing compound reacts with the surface of the metal oxide/hydroxide particles to form the desired monolayer thereon. 1-14 by reacting a metal oxide/hydroxide with an organophosphorus-containing compound such as a phosphonic acid or a phosphinic acid and is non-wettable in an aqueous medium. The present invention provides a method for forming a .

Example 6 The alumina used is 148 m”/# of nitrogen B, ]lf
i,T.

The surface area was woelm N 3-6.3-6 micromeddle particle size activated alumina. X-ray diffraction confirmed it to be mostly chialumina with traces of bayerite.

Two 20. One of the V samples was monodecyl phosphate ((012I(2)O)PO(OH)
2), and the other was didodecyl phosphate [(013H
250) 2 PO (OH). Each sample was treated with 50
Bath each sample in 0-14 M toluene for 2 hours at 92°C.
mixed with d. Each reaction mixture was then vacuum filtered to separate the solids. The solids from each mixture were then washed with six flushes of fresh toluene to remove unreacted organophosphonic acid.

The sample was then dried under vacuum at 60° C. for over 8 hours. The samples were then analyzed (by direct current plasma spectroscopy) in nitric acid solution for carbon by combustion and for phosphorous in nitric acid solution. The results are summarized in the table below.

Sound Sound Example 7 The product of Example 6 was mixed with monomethyl phosphate ((OH30)PO(OH)2) and dimethyl phosphate ((
OH3032PO(OH)] to react with the inaccessible alumina surface with mono- or didotecyl phosphoric acid. The methyl phosphate mixture was dissolved in deionized water.

The material from Example 6 was added at 40°C to about 0% of the methyl phosphate mixture.
62 M solution 62-. The reaction continued for 2 hours after wetting the material from Example 6 with the solution. (These are difficult to wet with aqueous solutions, indicating that the particle surface is sufficiently covered with hydrocarbon groups). The product solids were then vacuum filtered and washed with three displacements of deionized water.

This material was dried under vacuum at 60° C. for over 8 hours.

The composition of the product is shown here.

Experiment number Experiment number 22661-48A-122<561-48B-1 Source of starting solid 22661-48A 22661
-48B starting weight i(,y) zo, o6 2a
-a3 Weight of recovered product t(,9) 19.80
20.27 Product weight% P 1.70 1.66 N loss%
C! 7.57 8.58 The proportion of phosphorus increases in both alumina samples, which is consistent with an increase in the proportion of surface area covered by organophosphoric acids. Note that the increase in phosphorus content is much greater than in the t'L material treated with didodecyl phosphate (2261-48B to 2261-48B-1).

Each treated alumina (2261-48A-1 and 226
A portion of 1-48B-1) was used to prepare a column for liquid chromatography.

Each column was prepared with 60 volumes of acetonitrile, 60 volumes of methanol, and 40 volumes of water.
A mixture of methyl benzoate, phenetol and Q-xylene can be separated.

A column packed with a substance made from monodecyl phosphate <22661-48h-1) was 37
．． yielding a theoretical plate of 000 to 38.00 [ ];
- Substances prepared from zodotecyl tenthate (22651
Columns packed with -48B-12 ranged from 31,000 to 32. [ ] 00 theoretical plates were generated.

Columns packed with monodecyl phosphate treated alumina (22661-48 mu-1) also showed excellent resistance to strongly alkaline solutions (pi = water replaced with 10.0 carbonate buffer). .16
After hours this remained unchanged, and the column packed with alumina treated with didotecyl-percentate (2261-48B-1) completely failed before 16 hours of operation had been carried out.

Accordingly, the present invention provides a method in which approximately 0.0001 to 0.5 moles of the phosphorus-functional compound are reacted with the surface of the metal oxide/hydroxide particles to form the desired monolayer thereon.
By reacting metal oxide/hydroxide particles with phosphoric acid monoesters or phosphoric diesters at a temperature of 2 to 1, a reactive material is formed that can withstand a range of 2 to 11 and is non-wettable in aqueous media. It is further shown that a method is provided.

[Brief explanation of drawings]

FIG. 1 is a graph showing the weight percentage adsorbed on aluminum oxide/hydroxide forms as a function of acid concentration. Figure $2 is a graph showing the weight percentage of phosphorus adsorbed in the form of aluminum oxide/hydroxide as a function of aging time. FIG. 6 is a graph showing the rate of phosphorus remaining in solution after filtration as a function of aging time. FIG. 4 is a graph showing the weight percentage of phosphorus adsorbed on gamma alumina before and after cleaning as a function of acidity. FIG. 5 is a graph showing the IT percentage of phosphorus adsorbed on gamma alumina before and after washing as a function of aging time. FIG. 6 is a graph of - of bath liquid plotted against time as an indication of phosphorous adsorption on aluminum oxide/hydroxide particles. FIG. 7 is a flow sheet illustrating the present invention. FIG. 8 is a diagram of a metal oxide/hydroxide particle with a single li# of phosphorus-containing material on top, and FIG. 9A-9a is a plot of a chromatographic test run on a column containing a packing material of the present invention. be.

Claims (36)

[Claims] (1) Contains metal oxide/hydroxide particles in which a monomolecular layer of a phosphorus-containing organic material consisting of a phosphorus-containing group and a carbon-containing group is chemically bonded to reactive positions on the surface, and the bond is an active substance formed by the reaction of said metal oxide/hydroxide surface with said phosphorus-containing group, characterized in that said carbon-containing group is oriented away from said metal oxide/hydroxide surface. . (2) The phosphorus-containing organic substance has the formula RPO(OH)_2
and a phosphonic acid having the formula RR'PO(OH), where R
The active substance according to claim 1, which is a phosphinic acid having a carbon-containing group, or R' contains hydrogen or a carbon-containing group. (3) The phosphorus-containing organic substance has the formula (RO)PO(OH
)_2 or the formula (RO)(R'O)PO(
2. The active substance of claim 1, wherein R is a carbon-containing group and R is a carbon-containing group. (4) said monolayer of phosphorus-containing organic material comprises at least 25 of the reactive sites on said metal oxide/hydroxide surface;
% of the active substance of any of claims 1 to 3. (5) The metal oxide/hydroxide comprises particles having one or more of the following properties: (a) a particle size range of 50 angstroms to 12 millimeters; (b) the particles have a diameter of (c) the particles have a pore volume of about 0.1 to about 1.5 ml/g; and/or (d) the particles have an average pore size of about 1 to about 200 microns; 0.10 to about 1000m^2/g
An active substance according to any one of claims 1 to 3, having a surface area of . (6) The metal oxide/hydroxide particles are: 1) Part I
Group B, Group IIA, Group IIB, Group IIIA, Group IVA, Group VA, Group IIIB, Group IVB, Group VB, Group VIB,
Group VIIB or Group VIII metals: oxides/of elements capable of forming oxides/hydroxides from the lanthanide series, silicon, thorium, boron, uranium, selenium, arsenic or tellurium.
2) contains oxides/hydroxides of metals consisting of aluminum, magnesium, titanium, zirconium, iron, silicon, chromium, zinc, vanadium, or combinations of these metals; or 3) alumina. , iron oxide, silica, zeolitic materials, zirconia, zinc oxide, magnesia, apatite, or hydrotalcite. 7. The active material of claim 6, wherein the metal oxide/hydroxide particles include alumina. (8) the alumina (a) comprises activated alumina having a surface area within the range of 0.1 to 600 m^2/g; and/or (b) has a particle size within the range of 50 angstroms to 12 millimeters. The active substance of claim 7 comprising: (9) the thickness of said monolayer of phosphorus-containing organic material chemically bonded to said metal oxide/hydroxide particles is 10
5,000 angstroms, or 20 to 500 angstroms. (10) Claims 1 to 3, wherein the R group of the phosphorus-containing organic molecule contains at least 5 carbon atoms.
An active substance in any of the following. (11) Either the R group or the R' group is a long chain or short chain aliphatic hydrocarbon, an aromatic hydrocarbon, a carboxylic acid,
Aldehydes, ketones, amines, amides, thioamides, imides, lactams, anilines, pyridines, piperidines, anhydrides, carbohydrates, esters, lactones, ethers, alkenes, alkynes, alcohols, nitriles, oximes, organosilicones, sulfur-containing organic compounds, urea , thiourea, perfluoro, perchloro, perbromo organic molecules or combinations of these groups. (12) Either the R group or the R' group is a carboxyl group, such as a carboxymethyl group, a glucose group,
Monoclonal antibodies, cyano groups, cyanate groups, isocyanate and thiocyanate groups, phenyl groups, diphenyl groups, tert-butyl groups, sulfonic groups, benzylsulfonic groups, protein groups such as protein A (staphylococcal protein A), pharmaceuticals compounds, yeast, microorganisms,
consisting of whole cells, enzyme groups, dye groups, chelated metal groups, tag molecules, halogen groups, nitrate groups, phosphate groups, phosphinate groups, phosphinite groups, phosphonate groups, quaternary ammonium bases, or combinations of these groups; 12. Active substance according to claim 11, having a functional group added to a part of said molecule remote from said phosphorus-containing group on said molecule. (13) said R group or said R' group is added to a part of said molecule remote from said phosphorus-containing group on said molecule and -HSO_3, -N(CH_3)_3Cl, -
12. The active substance of claim 11, having a cation exchange functionality selected from the group consisting of COONa, -NH_2 and -CN. (14) Claims 1, 2, or 3, wherein said monomolecular layer of an organic material having a phosphorus-containing group does not substantially contain hydroxyl groups after chemically bonding to said metal oxide/hydroxide particles. Active Substances of Section 3. (15) Chromatographic packing material comprising one or more monolayers of phosphonic acid bound to a particulate metal oxide/hydroxide support material. (16) The chromatographic packing material of claim 15, wherein said metal oxide/hydroxide comprises aluminum oxide/hydroxide. 17. The chromatography of claim 15, wherein said particulate metal oxide/hydroxide support material has a particle size range of about 0.5 to about 300 microns, or about 1 to about 80 microns. filling substance. (18) the particulate metal oxide/hydroxide support material has a thickness of from about 20 to about 10,000 angstroms, or about 4
18. The chromatographic packing material of claim 17 having a pore diameter range of 0 to about 1000 angstroms. (19) about 0.1 to about 2 ml/g, or about 0.3 to about 1.5 ml/g of said particulate metal oxide/hydroxide support material;
16. The chromatographic packing material of claim 15, having a pore volume of ml/g. (20) The metal oxide/hydroxide particles are 1) I
Group B, Group IIA, Group IIB, Group IIIA, Group IIIB, Group
Group IVA, Group IVB, Group VA, Group VB, Group VIB, Group
Group VIIB or Group VIII metals; oxides/hydroxides of elements capable of forming oxides/hydroxides of the lanthanide series, silicon, thorium, boron, uranium, selenium, arsenic or tellurium; or 2) aluminum 20. The chromatograph of claim 19, comprising an oxide/hydroxide of a metal selected from the group consisting of: , magnesium, titanium, zirconium, iron, silicon, chromium, zinc, vanadium, and combinations thereof. Graph filling substance. (21) said monolayer of said one or more phosphonic acids bound to said particulate support material of: (a) formula RPO(OH)_2, where R is 5 to 30 carbon atoms; from about 2 to about 97% of one or more phosphonic acids having the formula R'PO(OH)_2 (wherein R' is a 1-4 carbon saturated or unsaturated aliphatic hydrocarbon. Graph filling substance. (22) 5 on the support material in an amount sufficient to cause the phosphonic acid having the formula R'PO(OH)_2 to react with the remaining reactive hydroxyl positions on the support material. Chromatography according to claim 21, consisting essentially of methylphosphonic acid, which after reaction between said one or more phosphonic acids having ~30 carbon atoms is reacted with hydroxyl groups on said support material. filling substance. (23) (a)i) Phosphonic acid with formula RPO(OH)_2; (ii) Phosphinic acid with formula RR'PO(OH); (iii) Phosphoric acid with formula (RO)PO(OH)_2 monoester; or (iv) formula (RO)(R'
O) phosphoric diester with PO(OH) (where R
is a carbon-containing group and R' is a carbon-containing group. The metal oxide/hydroxide is contacted with the liquid so as to chemically bond the phosphorus-containing material to at least 25% of the reactive sites on the oxide/hydroxide, and the organic material is deposited on top of the metal oxide/hydroxide. forming a monolayer of phosphorus-containing organic material to form an active material. (24) providing a liquid contained therein to an organic substance having 1 to 2 phosphorus-containing groups thereon, further comprising a concentration of at least about 0.1 mole of said phosphorus-containing organic substance in said liquid; 24. The method of claim 23, comprising retaining. (25) said step of contacting said metal oxide/hydroxide particles with said liquid containing said phosphorus-containing organic material further comprises maintaining said contact for about 0.1 to about 20 hours; , the method of claim 23. (26) said step of contacting said metal oxide/hydroxide particles with said liquid containing said phosphorus-containing organic material further comprises maintaining said contact for about 0.5 to about 4 hours; , the method of claim 25. (27) said step of contacting said metal oxide/hydroxide particles with said liquid containing said phosphorus-containing organic material, further including a temperature of said reactants of about 5 to 150° C. during said contacting step; 24. The method of claim 23, comprising maintaining. (28) The method of claim 23, wherein the metal oxide/hydroxide particles and the phosphorus-containing organic material are as defined in any of claims 5 to 14. (29) the monolayer comprises the phosphorus-containing organic material chemically bonded to the metal oxide/hydroxide particles;
29. The method of claim 28, comprising from 0.01 to 90% by weight of said active substance. (30) the monolayer comprises the phosphorus-containing organic material chemically bonded to the metal oxide/hydroxide particles;
29. The method of claim 28, comprising about 4 to 50% by weight of said active substance. (31) (a) a particulate metal oxide/hydroxide support material having a particle size range of about 0.5 to about 300 microns and the formula RPO(OH)_2, where R is 5 to 30 saturated or unsaturated aliphatic hydrocarbons or aromatic hydrocarbons) to form a monolayer of said one or more phosphonic acids on the surface of said particulate support material. and (b) in an amount sufficient to form chemical bonds with all remaining reactive hydroxyl positions on said support material; is a saturated or unsaturated aliphatic hydrocarbon of 1 to 4 carbons). A method of producing an active substance for use as a characterized chromatographic packing material. (32) Particulate metal oxide/hydroxide having a pore diameter range of about 20 to about 100,000 angstroms, a pore diameter range of about 40 to about 1000 angstroms, and a pore volume of about 0.1 to about 2 ml/g. 32. The method of claim 31, further comprising the step of providing a support material. (33) said step of reacting said particulate support material with one or more phosphonic acids having the formula R'PO(OH)_2 further comprises reacting said particulate material with methylphosphonic acid; The method of claim 31. 34. The method of claim 31, wherein the concentration of said phosphonic acid is from about 0.0001 to about 0.1 molar. (35) In each of the above steps, from about 5 to about 200
The phosphonic acid is reacted with the support material for no more than about 1 to about 20 hours in a non-aqueous medium at a temperature up to 32. The method of claim 31, forming a monolayer. (36) In each of the above steps, from about 25 °C to about 9 °C
The phosphonic acid is reacted with the support material in an aqueous medium at a temperature of up to 0°C for a period of time not exceeding about 20 hours to form the phosphonic acid onto the metal oxide/hydroxide support material. 32. The method of claim 31, forming a monolayer.