This invention relates to novel compositions including, in one aspect, novel compositions useful as separations media.

Separations media for separation process applications, including separations column packing materials for reverse phase chromatography columns, can be supplied from organic resins. However, these organic resin packing materials have certain draw¬ backs including poor physical strength, poor thermal stability, high cost, solvent swelling, and low capacity.

Separations media including chromatographic packing materials made from metal oxides overcome some of the problems related to organic resins but have some problems of their own. For example, silica-based separations column packing materials exhibit poor chemical stability at high pH values. Although silica-based separation materials are dominant in the marketplace for reverse phase column packings, silica-based separation materials have shortcomings of a relatively narrow operating pH range, e.g., such as about 2-8, and a high pressure drop require¬ ment through the separations column. The narrow operating pH range of silica-based separation materials usually results in shorter column life, loss of separations versatility, and dif¬ ficulty in the cleanup with strong alkali and acid for cost effec¬ tive, high speed analytical, semi-preparative and preparative purification of samples. A high pressure drop of the

silica-based materials also limits the ultimate speed and separa¬ tion capabilities of the chromatography column.

Metal oxides such as alumina have been used as adsor¬ bents because of good physical integrity and low cost. Aluminas have been used frequently as separations media, including separa¬ tions media in classical adsorption chromatography. However, the use of aluminas as separations media for modern high performance liquid chromatography in the reverse phase has not been as suc¬ cessful as silica. Reverse phase chromatography involves adsorp¬ tion on an adsorbent less polar than the eluting solvent. Con¬ trastingly, normal phase chromatography involves an adsorbent more polar than the eluting solvent. In reverse phase chromatog¬ raphy, the more non-polar sample components interact more with the relatively non-polar column packing and thus elute later than polar sample components. The diminished use of aluminas as separa¬ tions media in high performance chromatography in the reverse phase is because alumina is not easily converted to a hydrophobic phase for selective chromatographic separations via chemical bond¬ ing the surface by various hydrocarbon groups, e.g., alkyl or phenyl. Most silanization reagents used successfully with silica show no reactivity toward aluminas. Although chlorosilanes react with alumina, the formed Al(-O-Si-C) bond is known to be highly unstable under reverse phase chromatographic conditions.

U.S. Patent No. 4,045,353 discloses that the prior art suggests solid supports having cores coated with a porous silica surface and solid supports coated or chemically bonded with an

organic compound or organic polymer gel have been used to meet the requirements of high speed liquid chromatography. The patent discloses a solid support prepared by immersing an inorganic sub¬ strate in a radiation-polymerizable monomer. Suitable polymerizable monomers include the ethylenically unsaturated monomers, e.g. such as styrene monomer, fluorine monomer, silicon-containing monomer, acrylates, methacrylates, vinyl monomer, olefin monomers, diene monomers, e.g., such as ' butadiene, isoprene, 1,3-pentadiene, cyclopentadiene, chloroprene, or other monomers capable of being radiation polymerized such as the aldehydes, ketones, cyclic ethers, or the like. Such a polymer can be grafted (the patent discloses) on a substrate of "silica, silica gel, alumina, diatomaceous earth, zeolite, porous glass, carbon black, active carbon, clay, etc." It is an object of the present invention to provide novel

_* materials useful as separations media in a packed bed.

It is another object of the present invention to provide a novel composition useful as a reverse phase chromatographic column packing material.

It is a further object of the present invention to provide a reverse phase chromatographic column packing material which overcomes the problems of prior art column packing materials.

These and other objects of the present invention will become apparent from the detailed description which follows.

Summary of the Invention The invention includes novel separations material of stable polybutadiene coated and crosslinked on a surface of generally spherical metal oxide/hydroxide support particles comprising crys¬ tals of metal oxide/hydroxide with the crystals extending radially outward from a central core region and having a shape selected from principally acicular to principally lamellar. A chromatographic packing material for performing high performance liquid chromatography in the reverse phase of polybutadiene coated on alumina in accordance with the present invention provides highly symmetrical chromatographic peaks.

Brief Description of the Drawing The sole Figure presents a comparison of chromatograms show¬ ing chromatographic peaks obtained frqm commercially available packing materials compared to the novel separations material of the present invention.

Detailed Description The novel separation materials of the present invention in¬ clude a stable polybutadiene coated and crosslinked on a par¬ ticular alumina. The particular alumina of the present invention is characterized as a generally spherical aluminum oxide particle comprised of solid crystals of aluminum oxide with the crystals extending radially outward from a central core region and having a shape selected from principally acicular to principally lamel¬ lar. The material of the present invention is synthesized by coat¬ ing and immobilizing polybutadiene on said alumina. The immobi¬ lization is achieved by crosslinking with

chemical radical reactions, initiated by thermal decomposition of radical starters (generators) such as including dicumylperoxide. The separations material of the present invention includes polybutadiene in the amount of 5-208 by weight and preferably 8-10% by weight on the particular alumina in accordance with the present invention.

The present invention includes a stable polybutadiene coated and crosslinked on an alumina support base wherein the alumina contains acicular or lamellar alumina and is characterized as an alumina having a habit or form of crystals formed during a precipitation of aluminum hydroxide from an alkali metal aluminate by preselecting and controlling the pH of the alkali metal aluminate and the addition of certain monohydric and polyhydric alcohols to the alkali metal aluminate solution. Precipitation is controlled to form crystals having a habit or form which varies from principally acicular to principally lamel¬ lar crystal ,forms. The term "particle morphology" or "habit" are synonymous with the shape or form of a crystal, e.g., lamellar, tabular, equant, columnar, or acicular, as opposed to the crystal structure or system, e.g., tetragonal, orthorhombic, or monoclinic. While the crystal structure determines the number and types of crystalline faces, the morphology or habit is deter¬ mined by the relative growth rates of the crystalline faces, with the fastest growing faces disappearing while slower growing faces define the final shape. This alumina is formed by controlling the morphology or habit of aluminum hydroxide crystals to permit the respective free production of crystals

which are principally lamellar in the form of flat platelets or principally acicular in the form of needle-like structures as well as intermediate forms. The alumina used in the present inven¬ tion sometimes is referred to as Alcoa Wilhel y alumina. A more complete description of the alumina is provided in the related co-pending U.S. patent application by Richard B. Wilhelmy, U.S. Serial No. 022,735 filed March 6, 1987, which is hereby incor¬ porated by reference and intended to be a part hereof as if it had been included in its entirety. This patent application, U.S. Serial No. 022,735, currently is under notice of allowance.

The present invention includes the production of a uniform, crosslinked polybutadiene coating on the particular alumina particles by producing a polybutadiene coating and immobi¬ lizing the polybutadiene coating on the alumina by polymeric crosslinking. Immobilization in the present invention is per¬ formed by crosslinking with radical reactions, initiated by a thermal decomposition of radical starter. In one aspect, the radi¬ cal starter can be provided by dicumylperoxide.

TESHEET

IIC-CH CH-, CH ₃ HC-CH HC-CH CH ₃ S I I t S I

HC C-C-O-O-O CH HC C-— C-0 ^«

N / I I \ / N / I

HC-CH CH ₃ CH ₃ HC-CH HC-CH CH ₃ dicumylperoxide radical

cross-linked polybutadiene

ON ALUMINA SUBSTRATE

The present invention provides novel separations materials which are particularly useful As stable alumina-based reverse phase packing material for liquid chromatography. The material of the present invention is prepared by coating and immo¬ bilizing polybutadiene on the particular alumina of the present invention, and several important factors must be controlled in the preparation of stable and efficient polymer coated and crosslinked reverse phase pack material. My related co-pending U.S. patent application filed on even date herewith discloses producing the material of the present invention and is hereby incorporated by reference.

The alumina-based separations media in accordance with the present invention have many advantages over silica for liquid chromatographic applications. The advantages of using the alumina-based supported separations media of the present invention include a wide pH stability for the separation of many acidic and basic compounds by ion-suppression rather than by ion- pairing techniques. The advantages of the present invention fur¬ ther include a low pressure drop requirement for chromatography column process applications.

The chromatographic behavior of this packing material has been tested extensively for efficiency, selectivity, and stability, both in long term stability and chemical stability in comparison with various reverse phase packings. The packing material of the present invention outperforms silica-based reverse phase packings with a lower pressure drop, wider pH stability, and less peak tailing for the separation of basic

compounds. Separations for aromatics, anilines, purines, pyrimidines, and nucleosides have been found to provide good resolution with the packing material of the present invention. My related copending U.S. patent application filed on even date herewith discloses process parameters in high performance liquid chromatography in the reverse phase for using chromatographic packing materials in accordance with the present invention.

In contrast to the silica-based support material for chromatography, the present invention provides novel separation materials of polybutadiene on alumina which is stable at a rela¬ tively high pH. The present invention provides a material useful over a wide pH range, e.g., such as 2-12. The present invention also provides a material which overcomes the problems associated with alumina-based support materials in forming a hydrophobic phase. The present invention provides a material which has only low pressure drop requirements in packed columns.

The chromatography column can be packed, by way of ex¬ ample, using a 20 ml sample of isopropyl alcohol containing about 2-3 g of particles sonicated for at least 15 minutes and added to the packing reservoir, the reservoir being connected to the column arranged in downward configuration. Coated particles are forced into the column at 6,000 psi with methanol as a loading solvent. Packing should be consolidated until a constant flow rate of methanol reaches equilibrium (approximately 10 minutes) . Pressure should be allowed to bleed off the outlet, and the column disconnected from the packer. Excess particles can be scraped carefully from the top face of the column, and a

fitting containing a stainless steel frit attached to the column inlet.

Referring to the Figure, chro atograms (from published literature) are depicted for the separation of aniline, n-methylaniline, and n,n-dimethylaniline on various packing materials including adamantyl bonded on silica (A) , octadecyl bonded on silica (B) , octyl bonded on silica (C) , octyl bonded on silica (D) , and (from experimental using a Beckman liquid chromatograph) for polybutadiene coated and crosslinked Wilhelmy alumina. Peak shapes obtained from the stable polybutadiene coated and crosslinked alumina in accordance with the present in¬ vention were superior to those obtained from adamantyl or the com¬ mercially available octyl or octadecyl bonded on silica. Superior is determined by a tailing characteristic for each solute evaluated by calculating the asymmetric factor as the ratio of rear or tailing part to the front part of the peak at 10% peak height. Calculations of this characteristic factor are presented in Table I. Table I presents asymmetry factors for the packing material of the present invention compared to various prior art reverse phase packing materials including adamantyl bonded on silica, octadecyl bonded on silica, and octyl bonded on silica. The prior art asymmetry factors are taken from published literature. All asymmetry factors were obtained under identical mobile phase composition (50% water/50% methanol) for all the columns.

TABLE 1

Packing Solutes aniline n-methylaniline n.n-dimethylaniline p-toluidine o-toluidine m-toluidine p-chloroaniline

adamantyl 2.4 2.7 3.3 4.0 2.8 3.0 1.9 (10 μm) octadecyl 12.8 14.8 17.0 4.9 9.0 5.1 4.3 (5 μm) octyl 7.5 13.4 14.3 13.2 8.5 11.1 5.9 (5 μm) ) octyl 4.3 4.4 5.3 6.0 5.1 4.1 3.4 (5 μm) octadecyl 14.2 12.9 16.2 19.6 5.2 6.9 4.1 (5 μm) octyldecyl 7.9 8.1 15.2 17.4 8.4 11.7 4.1 (5 μm) octadecyl 10.1 11.5 13.1 9.8 5.5 3.1 3.5 (5 μm) octyl 11.1 11.2 13.7 5.5 9.8 7.5 7.5 (10 μm) octadecyl 18.8 23.5 28.0 18.7 21.8 20.2 16.1 (3 μm)

PB0 coated 1.1 2.0 2.3 1.5 2.2 1.9 1.6 and cross¬ linked on Uilhelmy Alumina

Example 1 Varying amounts of three to fifteen grams (3-15 g) of alumina sometimes referred to as Wilhelmy alumina or Alcoa Wilhelmy alumina obtained from the Alcoa Technical Center, Alcoa Center, Pennsylvania 15069 were suspended in a 250 ml round flask in 100-150 ml of n-pentane solution containing 10% to 20% by weight of polybutadiene oligomer (molecular weight of about 3400) and 2% of dicumylperoxide by weight with respect to the polybutadiene. Polybutadiene was phenyl terminated, 99% un- saturated, 25% vinyl, 40% trans-1,4, average molecular weight of about 3400 and 45% vinyl, 55% sis and trans 1,4, average molecular weight of about 4500.

Sonication was applied to the mixture for about 30 minutes. The pentane was evaporated slowly with the rotary evaporator connected to an aspirator to accelerate the evapora¬ tion process. The evaporation process was carried out at ambient temperature to prevent losing the activity of dicumylperoxide. The polybutadiene coated alumina was transferred into a stainless steel column and purged with dry nitrogen at a flow rate of about 10 ml per minute overnight. Crosslinking was performed by elevat¬ ing the oven temperature to about 170°C at a rate of about 5°C per minute and held for 2 hours. Polymer coating and crosslinked particles produced by this procedure were washed with up to about 200 ml each of heptane and methylene chloride to remove unreacted polybutadiene. The washed particles were placed into the flask and dried with a rotary evaporator for at least about 4 hours.

The polybutadiene coated Alcoa Wilhelmy alumina was analyzed and the physical characterization of the particles is presented in Table II.

TABLE II Physical Characteristics of Alcoa Wilhelmy Alumina Before and After PBD Coating Parameter PBD Coating before after

% PBD Loading 0 9%

Average Particle Diameter, micrometers 9 9

Surface Area, m2/g 37.12 29.58

Particle size generally did not change before and after coating. The accumulative mass percent particle size distribution plots for the Alcoa Wilhelmy alumina before and after polybutadiene coating are illustrated in Figure 1. The average particle size of the Alcoa Wilhelmy alumina was around 9 microns, and at least 50% of the particles were in the size range of 8 to 10 microns.

A scanning electron micrograph of polybutadiene coated Alcoa Wilhelmy alumina revealed no structural defects of particles after coating and crosslinking (from the spherical and relatively narrow particle size distribution of bare Alcoa Wilhelmy alumina). The micrograph is illustrated in Figure 2.

An electron micrograph of the particles at higher magnification is shown in Figure 2 also.

Surface area was determined by nitrogen BET. The sur¬ face areas of bare Alcoa Wilhelmy particles and 9% polybutadiene coated Alcoa Wilhelmy particles were about 37.12 /g and about 29.58 m /g, respectively. A decrease of about 20% was observed after coating. The decrease of surface area was attributable to the plugging of small pores by the polybutadiene oligo ers. Smaller molecular weight polybutadiene oligo er can be used to reduce pore plugging.

Example 2 Basic compounds have severe peak asymmetry problems for octadecylsilyl bonded on silica in packed columns. The effect is attributable to the presence of residual, non-silylated, silanol groups on the surface of column material. Some ways to overcome peak tailing problems are end capping the surface silanols by reacting derivatized surfaces with a smaller molecule silanizing reagent, such as trimethylchlorosilane, using mobile phase addi¬ tives to reduce the concentration of accessible silanols by strongly sorbing to the surface, and via steric exclusion of the solutes from reaching the surface of column material. Although improvements in peak symmetry have been obtained, these ap¬ proaches do not provide a total solution to the tailing problems. To test the performance of the stable polybutadiene (PDD) coated Alcoa Wilhelmy particles of the present invention, aniline, n-methylaniline, n,n-dimethylaniline, o-toluidine,

m-toluidine, p-toluidine, and p-chloroaniline were used. The Figure illustrates the chromatograms obtained from adamantyl (A) , octadecyl (B) , octyl (C) , octyl (D) , and PBD coated Alcoa Wilhelmy particle phases for the separation of aniline, n-methylaniline, and n,n-dimethylaniline. The peak shapes obtained from the PBD coated Alcoa Wilhelmy particle column were superior to those obtained from either adamantyl or the commer¬ cially available octyl or octadecyl phases. The peak tailing characteristic for each solute was evaluated by calculating the asymmetric factor as the ratio of rear part to the front part of peak at 10 percent peak height. Results from this calculation are listed in Table I hereinabove. Columns are either made (adamantyl) or tested of commercial columns (including IBM oc¬ tadecyl, IBM octyl, Altex Ultrasphere octyl, Alter Ultrasphere octadecyl, Supelco octadecyl, octyl, Hibar octyl, Perkin-Elmer octadecyl phases) . All the asymmetry factors obtained were under identical mobile phase composition (50 percent H ₂ 0/50 percent M _e 0H) for all the columns. Asymmetry factors for the novel com¬ position of the present invention are much smaller than those ob¬ tained from the adamantyl column or any commercial column.

While the invention has been described in terms of preferred embodiments, the claims appended hereto are intended to encompass all embodiments which fall within the spirit of the in¬ vention.

What is claimed is:

HEET