EP1085941A2

EP1085941A2 - Combinational method for microgram-scale production and characterization of crystalline and amorphous libraries of materials

Info

Publication number: EP1085941A2
Application number: EP99924959A
Authority: EP
Inventors: Wilhelm-Friedrich Maier; Jens Klein; Christian Lehmann; Hans-Werner Schmidt
Original assignee: Studiengesellschaft Kohle gGmbH
Current assignee: HTE AG HIGH THROUGHPUT EXPERIM
Priority date: 1998-05-16
Filing date: 1999-05-12
Publication date: 2001-03-28
Also published as: US6825048B1; JP2002515327A; CA2333178A1; WO1999059716A2; DE19822077A1; WO1999059716A3

Abstract

The invention relates to a method for wet chemical production of a plurality of libraries of materials consisting of solids, whereby the solids are separated from reaction mixtures in microreaction chambers on a base plate serving at the same time as substrate for the library. Depending on the material chosen for the substrate of the library, solids can be subsequently investigated in a non-destructive manner, e.g. by means of reflecting or penetrating microarea X-ray scattering.

Description

Combinatorial process for the production and characterization of crystalline and amorphous material libraries in microgram

scale

The present invention relates to a process for the wet chemical production of material libraries consisting of a large number of solids, the solids being separated from reaction mixtures in microreaction chambers on a base plate which also serves as a library substrate.

The greatest bottleneck in the development of new active ingredients, polymers and materials is the discovery of suitable new lead structures. In the fields of organic, biochemical and pharmaceutical chemistry, combinatorics has established itself as an important tool for the development of new compounds within a few years (e.g. Special issue: Combinatorial Chemistry, Acc. Chem. Res., 1996, 29; G. Löwe, Chemical Society Reviews, 1995, 24 (5), 309; SR Wilson, AW Czarnik, Combinatorial Chemistry - Synthesis and Application, John Wiley & Sons, 1997). In contrast, only a few examples are known in the field of inorganic solid-state synthesis or material research or technical catalyst development, in which the combinatorial material search is used. The production of material libraries by combinatorial syntheses has been reported, with the aim of new superconducting materials (X.-D. Xiang et al. Science, 1995, 268, 1738), new magnetoresistant materials (G. Briceno et al., Science, 1995, 270, 273) and new luminescent materials (E. Danielson et al., Science, 1998, 279, 837). All these processes have in common that the application of the substances as thin films via electron beam evaporation or RF sputtering under reduced pressure leads to the formation of a material library. A physical mask has a formative effect, which has already led to libraries of up to 25,000 materials. The first combinatorial generation of a material library using the wet-chemical method using ink-jet technology led to the development of luminescent materials (D. Sun et al., Adv. Mater. 9, 1046-1049, 1997). The disadvantage is that this method can only be used at normal pressure and low temperatures.

Many of the previously known materials, especially the porous substances important for catalysis, can only be wet-chemically, often by the hydrothermal method (e.g. MW Anderson et al., Angew. Chem., 1995, 107, 1115; DP Serrtano et al., Microporous Materials , 4 (1995), 273). The methods differ only in the selected temperature and pressure ranges, the variation in the stoichiometric ratios of the selected precursors and in the choice of template molecules (L. D. Rollmann, Inorganic Compounds with unusual Properties-Il, 1979, 387). Depending on the sample volume and the test procedure, a synthesis under hydrothermal conditions takes 2 hours to several weeks. The product is also refurbished and characterized. The most important analytical method here is powder diffraction to clarify the phase structure. Of particular importance for the use of such materials in areas such as catalysis or sensor technology is their pore architecture, which can be controlled by adding template molecules in hydrothermal synthesis. The large amount of time per synthesis and the variety of possible mixed oxides and template molecules has made any systematic and exhaustive investigation of these material classes impossible. Due to the multitude of possibilities of polynary mixtures of oxidic materials as well as the generally possible template molecules for influencing the pore architecture of such substances, it is attractive to transfer the methods of combinatorial chemistry to hydrothermal synthesis.

Akporiaye, Karlsson and Wendelbo (DE Akporiaye, IM Dahl, A. Karlsson, R. Wendelbo, Angew. Chem., 1998, 110, No. 5, 629; DE Akporiaye, IM Dahl) reported on the first use of combinatorial methods in hydrothermal synthesis , A. Karlsson, R. Wendelbo, patent pending, Norwegian application number 97.0788). They developed an autoclave with which 100 hydrothermal syntheses (reaction volumes of 500 mL each) can be carried out at temperatures up to 200 ° C. The disadvantage is that this process does not generate a material library, but the resulting solids must be removed from the individual mini-reactors and individually characterized by default. This handling of the samples after synthesis proves to be very cumbersome and crucially limits the strength of this combinatorial approach.

We have now found that material libraries with minimal amounts of material (reaction volumes of 2 μL or less) can be produced by wet chemistry. For this purpose, the z. B. are introduced in the form of holes in a plate ("reaction plate"), brought a large number of reaction mixtures of different composition to react simultaneously, the solids produced being deposited on the reactor bottom plate underneath. The solids are then freed from the supernatant liquid phase , calcined and then adheres locally to the base plate. By suitable choice of the material of the reactor base plate, this can simultaneously serve as a library substrate. Alternatively, the solids, or a part thereof in each case, can be transferred to this by means of a film provided with an adhesive layer, so that a copied material library with another library substrate is created.

Depending on the choice of the material of the reactor base plate or the film, different analytical methods can be used to characterize the solids. B. the reflective micro-range X-ray diffraction, if the base plate consists of X-rays elastically scattering material that causes little scattering. Suitable materials for this are single-crystalline plates, preferably made of Si, Cu, quartz, rutile, anatase, zirconium dioxide, Ge, Al, sapphire, Fe, Ti, Zr, Co, Ni, or Sn, particularly preferably a (711) Si single crystal disk. For an examination with penetrating micro-range X-ray diffraction, radiatable materials are suitable, e.g. B. Kapton, Kevlar, Teflon, Mylar, PVC, polyethylene, polypropylene, polycarbonate, Al, Be or Mg in layer thicknesses <100 microns, preferably <10 microns. The reactor for generating the material libraries is built up in layers: above the reactor base plate, which can serve as a library substrate, there are at least two reaction plates made of inert material with bores of 0.05 - 20 mm in diameter, which serve as microreaction chambers. The top reaction plate consists of hard material, e.g. B. steel. There is a sealing layer without holes, e.g. B. made of Teflon, over it again a layer of hard material with which the reactor layers are compressed and sealed using suitable devices. With a suitable choice of the materials used, reaction temperatures of up to approx. 1000 ° C are possible; if Teflon is used for sealing, a maximum of 350 ° C is possible.

The reactor can be dimensioned very small with extremely small reactor volumes and meets the highest safety requirements. The sensible and practicable miniaturization of the material library is currently limited on the one hand by the focusability of the X-ray beam when measuring the X-ray diffraction and on the other hand by the dimensioning of the liquid dosage. While 10 samples per mm could already be analyzed with a smallest x-ray diameter of 50 μm (= 10,000 samples / cm ² ), only 5 samples per mm with a microreactor height of 10 mm can be realized with a dose quantity of 0.5 μL ( = 2,500 samples / cm ² = 2,500,000 samples / dm ² ).

By applying combinatorial techniques to synthesis optimization, systematic variations in composition and manufacturing conditions, solid synthesis can be quickly optimized and the discovery of new solids can be drastically accelerated. This allows material development in the normal laboratory to be carried out cost-effectively without additional safety measures. Due to its small dimensions, the reactor can also be easily handled in glove boxes under inert gas and, with appropriate modification, can be charged with reactive gases such as ammonia, chlorine, methane, borane, HCl, hydrogen, oxygen or fluorine, hermetically sealed and thus used to synthesize new materials deploy.

An automated examination of all solids in a material library produced in this way is e.g. B. by the phase identification of the individual materials using the commercial GADDS microdiffractometer from Bruker-AXS (M. Schuster, H. Goebel, Appl. Phys. 28 (1995) A270-A275; H. Goebel, PCT Int. Appl WO 9522758 A1) possible. This concept enables direct identification of the substances formed. There is no separate sample preparation for the measurement. In addition to the phase identification through the non-destructive micro-area X-ray diffraction, the complete library is available for further investigations such as catalytic activity via thermal difference images (Maier, Holzwarth, DE A19757 754.7 from December 23, 1997), luminescence, magnetic resistance and other characterizations.

The method relates in particular to the preparation or deposition of crystalline and amorphous solids from the liquid phase, such as solutions, emulsions, suspensions or sols. The areas of sol-gel synthesis (CJ Brinker, GW Scherrer "Sol-Gel Science, the Physics and Chemistry of the Sol-Gel Process", Academic Press, New York 1990), hydrothermal syntheses (Kirk- Othmer (3.) 6, 321), hydrometallurgy, decomposition of preceramic materials to produce hard materials (D. Segal, Chemical Synthesis of Advanced Ceramic Materials, Cambridge University Press, New York 1989) and polymerizations.

The inventive method is suitable for. B. for the discovery of new materials in the field of inorganic solids, in particular in the field of mixed oxides, mixed carbides, mixed nitrides and mixed borides. These materials are used in many areas of daily life and industrial production as lead structures for catalysts, light guides, coatings, semiconductors, superconductors, ferromagnetic materials, magnetic resistors, optical materials, hard materials, luminescent and fluorescent materials, sensors, NLO materials, special materials and a lot more. In particular, the substance class of crystalline, porous materials, such as that of the zeolites or the amorphous porous mixed oxides, mixed carbides or mixed nitrides, is of great interest to industry. They are used industrially as catalysts for oil refining in petrochemicals as well as for the production of pharmaceuticals, fine and large chemicals. They catalyze a wide variety of oxidation reactions: aromatic hydroxylation, olefin epoxidation, ketone ammoximation, alcohol oxidation and alkanoxy functionalization, to name just a few examples. The stable amorphous mixed oxides are similarly promising, their properties are just as important as those of crystalline substances, but their production is usually simpler than that of crystalline, well-defined materials.

Execution example:

Using the example of the combinatorial modification of a conventional, customary titanium silicalite synthesis under hydrothermal conditions (UK Patent 2071071 B), we show how a material library of crystalline and amorphous materials can be produced and analyzed with minimal expenditure of time.

The reactor used:

Figure 1 shows the construction drawing of the pressure-tight reactor. In a cylindrical pressure vessel made of steel (total diameter: 40 mm, inner diameter: 24.5 mm) with a height of 22.7 mm is a silicon single crystal disc with a diameter of 22 mm. A steel plate with Teflon insert is pressed onto this Si single-crystal wafer by 3 screws, the holes of which represent the reaction spaces. Figure 2 shows the grid with the corresponding distances. The various reaction solutions are pipetted into this mask using a robot or by hand (1 to 2μL). A further Teflon disc follows as a seal for the reaction, which in turn is pressed on with a thick steel plate using 3 screw connections, so that the entire arrangement is sealed pressure-tight. Experimental approach:

In a typical batch, 2.27 g (10.9 mmol) of tetraethyl orthosilicate (TEOS) is mixed in a 10 ml vessel with 75 mg (0.33 mmol) of tetraethyl titanate. 4 g (5 mmol) of a 25% by weight solution of tetrapropylammonium hydroxide are added to this solution with stirring and the mixture is stirred for 1 hour. After the alcohol formed has been completely evaporated after heating for 5-6 hours at 80-90 ° C., the solution is distilled with dist. Water made up to 7.5 ml and represents a typical reaction solution.

37 combinatorial modifications of the experimental approach were prepared according to the information in Table 1.

Hole mixture hole mixture

A1 Si: Ti: NPr ₄ OH D5 AI: Ti: CTAB 1: 0.03: 0.45 1: 0.05: 0.1

A2 Si: Ti: NBu ₄ OH D6 AI: Zr: NBu ₄ OH 1: 0.03: 0.45 1: 0.2: 0.4

A3 Si: Ti: NEt ₄ OH D7 AI: Zr: NMe ₄ OH 1: 0.03: 0.45 1: 0.2: 0.4

B1 Si: Ti: NMe ₄ OH E1 AI: Zr: NEt ₄ OH 1: 0.03: 0.45 1: 0.2: 1

B2 Si: Ti: C ₄ H ₉ N E2 AI: Zr: CTAB 1: 0.03: 0.45 1: 0.2: 0.1

B3 Si: Ti: CTAB E3 Ti: Zr: NBu ₄ OH 1: 0.03: 0.045 1: 1: 0.4

B4 Si: Ti: hexadecylamine E4 Ti: Zr NBu ₄ OH 1: 0.03: 0.045 1: 1: 0.4

B5 Si: Ti: hexadecylamine: NaO E5 Ti: Zr: NMe ₄ OH

H 1: 1: 0.4

1: 0.03: 0.045: 0.45

C1 Si: AI: NPr ₄ OH E6 Ti: Zr: NEt ₄ OH 1: 0.033: 0.43 1: 1: 1 C2 Si: AI: NPr ₄ OH E7 Ti: Zr: CTAB

1: 0.066: 0.43 1: 1: 0.1

C3 Si: Zr: NPr ₄ OH F1 Si: Ti: NPr ₄ OH

1: 0.03: 0.98 1: 0.03: 0.45

C4 Si: V: NPr ₄ OH F2 Si: V: NPr ₄ OH

1: 0.03: 0.45 1: 0.03: 0.45

C5 Si: Zr: NBu ₄ OH F3 Si: Ti: NEt ₄ OH

1: 0.03: 0.4 1: 0.03: 0.45

C6 Si: Zr: NMe ₄ OH F4 Si: Zr: NPr ₄ OH

1: 0.03: 0.4 1: 0.01: 0.98

C7 AI: Ti: NBu ₄ OH F5 Si: AI: NPr ₄ OH

1: 0.05: 0.4 1: 0.1: 0.43

D1 AI: Ti: NMe ₄ OH G1 Si: Ti: NPr ₄ OH

1: 0.05: 0.4 1: 0.03: 0.45

D2 AI: Ti: NEt ₄ OH G2 AI: Si: NPr ₄ OH

1: 0.05: 1 1: 0.2: 0.43

D3 AI: Ti: NEt ₄ OH G3 AI: Si: NPr ₄ OH

1: 0.05: 1 1: 0.1: 0.43

D4 AI: Ti: CTAB

1: 0.05: 0.1

Table 1: Composition of the material points of the library in Fig. 2. The "mixture" shows the molar ratio of the metal alkoxides used (and thus the oxidic materials in the product being formed) to the template molecule used. As sources for SiO ₂ , TiO ₂ , ZrO ₂ and AI ₂ O ₃ became tetraethoxysilane (Si (OEt) ₄ , TEOS), Ti (OEt) ₄ , Ti (O'Pr) ₄ or Ti (O ⁿ Pr) ₄ , Zr (O ⁿ Pr) ₄ and AI (O ^sec Bu) _3. Since after the evaporation of the alcohols the externally presented samples were filled up to 7.5 mL with distilled water, an excess of water: metal = 40: 1 is present in all samples for hydrothermal synthesis.

A1 and F1 each contain the original approach described above. Holes A1 - G3 (Fig. 2) are filled with 1 to 2 μL of the batches from Table 1. The “Mixture” represents the molar ratio of the metal alkoxides used (and thus the oxidic materials in the product being formed) to the template molecule used. Since the alcohols had been evaporated, the externally shown samples were made up to 7.5 ml with distilled water Excess water: metal: water = 1:40 before all samples for hydrothermal synthesis.

The reaction takes place in a closed reactor at a temperature of 200 ° C over a period of 36 h.

Post-treatment of the material library:

After the reaction, the upper steel and Teflon plate are lifted off, the products in the microreaction chambers are removed from the mother liquor by removing the supernatant liquid using conventional techniques, e.g. porous magnesia stick, separated. Ideally, of course, this is done in one operation using appropriate tools. Following this, the substances are washed several times with 2 μL dist. Washed water in the same way. The open reactor with the products can then be dried and, if Teflon is used as the reactor plate, calcined to a maximum of 350 ° C., preferably at 130 ° C., which leads to good adhesion of the solids formed to the reactor base. After removing the two steel reaction plates and the Teflon insert, the resulting material library (original base plate) can be further processed or examined. In the case of the zeolite synthesis sought here, the material library was annealed in an oven at 600 ° C. for 10 h. If the products are to be analyzed in a vertical arrangement, the adhesion of the samples can be improved by spraying a suitable amorphous lacquer on the library. This can then be evaporated again at elevated temperatures or removed by oxidation.

Identification of the solids:

The phases of the resulting products were identified with a

GADDS micro-range X-ray diffractometer with Göbel mirror and a HI STAR detector. The Si plate was attached to an xyz sample table and then, after entering the grid parameters and storing the points to be measured, measured automatically in reflection. The powder diffractograms were recorded integrally over the entire "spot" area with a 500μm collimator. The X-ray beam can be focused to 50μm with high X-ray intensity by means of a curved Göbel mirror. Individual particles in the micrometer range are therefore accessible for X-ray analysis. No reflections from the silicon sample carrier are found under the selected measurement conditions .. If a thin film is used as the reactor bottom or if the library is transferred to a thin film which is provided with an adhesive layer, the diffractogram can also be recorded in the transmission mode later evaluation saved and can be identified manually or fully automatically with comparison libraries.

The evaluation of the diffractograms showed that the dots with a gray background in Fig. 2 contain crystalline components, while all the dots not highlighted contain amorphous materials. The structure of the crystalline phases was identified by comparing their diffractograms with a diffractogram library. The reaction mixtures for producing the solids in points A1 and F1 correspond to the classic synthesis. In Fig. 3 the powder uptake of the conventionally produced zeolite (top) is compared with the diffractograms of points A1 and F1. The figure shows that the same material as in conventional synthesis was generated with microgram quantities from the material library.

Figure 1: Special version of the reactor as used in the exemplary embodiment.

Figure 2: Identification of the material library. The composition of the individual sample points are summarized in Table 1.

Figure 3: This figure shows an example of the X-ray diffraction diagram of a conventionally produced TS-1 zeolite and below it the X-ray scatter images identical to it, as obtained from the material library at the specified points of total substance amounts in the μg range, and thus confirms that crystalline inorganic materials such as zeolites can be produced and identified by the specified method.

Claims

claims

1. A process for the wet chemical production of a material library comprising a large number of solids from reaction mixtures of different compositions, characterized in that the reaction mixtures are introduced into a reactor and brought to reaction in locally separated microreaction chambers in removable reaction plates, the solids produced in the reactions separate on a removable reactor base plate.

2. The method according to claim 1, wherein the reaction mixtures in the form of solutions or suspensions in the microreaction chambers, which are introduced in the form of isolated cavities as bores in the reaction plates, are reacted at temperatures up to 1000 ° C. and internal pressures up to 1000 bar .

3. The method according to claim 1, wherein the solids deposited on the reactor base plate are then freed from the supernatant liquid phase and calcined.

4. The method according to claims 1 to 3, wherein the reactor base plate, which consists of X-ray elastically scattering material, is identical to the library substrate on which the solids are adhered, and together with the deposited calcined solids forms the material library.

5. The method according to claims 1 to 3, wherein a partial amount of all the separated solids is then drawn off onto a film provided with an adhesive coating, which consists of material which can be penetrated by X-rays and forms a library of materials together with the solids transferred thereon.