The invention relates to a process for the study of chemical reactions in the presence of potentially catalytic substances, in which the reactions are carried out in parallel in reactors. The invention further relates to an apparatus, in particular for carrying out this process, the apparatus having a plurality of parallel-connected reactors which are provided with feedlines and discharge lines.
Processes and apparatuses of said type are known and are used, inter alia, in the search for catalysts for the heterogeneous or homogeneous catalysis of industrial chemical processes.
However, most recently, novel techniques have made it posible to prepare substances in a great number, which could be potential catalysts for a multiplicity of chemical processes (P. G. Schultz et al., Science 1995, 1738). The study of this multiplicity of potential catalysts is scarcely possible any longer using the conventional series screening processes, since these screening processes are limited with respect to throughput and analytical resolution, as well as in reproducibility. Frequently, for pure activity screening, integral effects such as heating of the catalyst etc. are used completely inadequately without direct product mixture analysis or efficiency analysis. Furthermore, optimizing the conditions of catalyst activation and process procedure make special requirements of quantitative analytical processes and of the reproducibility of the reaction conditions.
The object underlying the invention was therefore to develop an inexpensive process or an inexpensive apparatus by which a multiplicity of chemical reactions can be studied in a short time and thus reproducible, qualitative and quantitative data can be obtained with respect to the composition of the different reaction mixtures and reaction products.
This object is achieved by a process of the type mentioned at the outset, which is characterized in that the reactions are carried out in miniaturized reactors and the reaction mixture or the reaction products are analyzed with respect to nature and amount during the reaction period.
The object is further achieved by an apparatus of said type, which is characterized in that the reactors are miniaturized, at a volume from the range from 0.001 cm3 to 1 cm3.
The invention thus relates to a process for the study of chemical reactions in the presence of potentially catalytic substances, in which the reactions are carried out in parallel in reactors, characterized in that the reactions are carried out in miniaturized reactors and the reaction mixture is analyzed with respect to nature and amount during the reaction period.
The invention further relates to an apparatus, in particular for carrying out this process, the apparatus having a plurality of parallel-connected reactors which are provided with feedlines and discharge lines, characterized in that the reactors are miniaturized, at a volume from the range from 0.001 cm3 to 1 cm3.
Particular embodiments or developments of the invention result from the corresponding subclaims. Individual or a plurality of individual features mentioned in the claims can also each themselves represent solutions of the invention, and the features within the claim categories can also be combined as desired.
A particular embodiment of the process according to the invention is characterized in that the reaction starting materials are fed continuously to the reactors and the reaction products are discharged continuously from the reactors. However, the batch mode of operation is equally possible.
A further particular embodiment is characterized in that use is made of starting materials which are at least in part labeled with isotopes, preferably with deuterium (2H) or heavy oxygen (18O) or heavy carbon (13C) or mixtures thereof. These generate characteristic spectral shifts in rotation-vibration spectra, which, in addition to labeling the reaction pathway, owing to starting material mixed variants, can lead to novel interesting reactions or reaction products and relatively small by-product contents can be contrasted systematically.
Individual reactors or reactors combined to form groups can also be fed with different starting material mixtures, in order to reveal or detect any synergies present in this manner using the methods of combinatory chemistry.
The starting material mixtures, reaction mixtures or product mixtures can be analyzed with respect to nature and amount of the substances present at any time points of the course of the reaction by spectroscopic analysis, preferably by infrared spectroscopy (IR), particularly preferably by Fourier IR spectroscopy. Other spectroscopic methods, such as laser spectroscopy or UV spectroscopy, are equally suitable for the study. The process can be carried out at differing temperatures and pressures, at temperatures of the range from xe2x88x9250xc2x0 C. up to and including 600xc2x0 C., preferably from room temperature to 500xc2x0 C., or at various pressures, at absolute pressures from 10xe2x88x923 to 103 bar, preferably from 10xe2x88x922 to 200 bar. The data obtained can then be supplied to a comprehensive parametric and data analysis.
The invention is further characterized in that the reactions can be carried out in the presence of a heterogeneous or homogeneous catalyst and in that it is possible to screen the catalytic activity (ie. product detection) and selectivity (main product distribution) of catalyst amounts less than 10 mg, preferably less than 1 mg, in a reactor.
In a particular embodiment of the apparatus according to the invention, a plurality of miniaturized reactors separated from one another can be disposed in a block. The volume of these reactors can be in the range from 0.001 cm3 to 1 cm3, preferably from 0.01 cm3 to 0.5 cm3, particularly preferably from 0.05 cm3 to 0.2 cm3. In a further preferred embodiment of the apparatus according to the invention, the reactors are disposed as a square or rectangular pattern in a metal block, which can be parallelepipedal or cubic. The metal block can be provided with heating block elements or cooling elements and can be fitted with a temperature sensor in the vicinity of each reactor. This makes monitored and reproducible temperature control possible. For example, by this means, a defined temperature gradient can be set over the metal block. The reactors are advantageously disposed in a plane which is parallel to a surface of the parallelepiped. Advantageously, at least some of the feedlines and discharge lines of the individual reactors are perpendicular to this plane. They can be designed as through-holes in the metal block. The reactors can be designed as boreholes. The number of reactors in one block can be greater than 20, preferably greater than 40, particularly preferably greater than 100, very particularly preferably greater than 200. Using these reactors, under defined reaction conditions, a small amount of potential catalysts (also termed samples below) can be brought into contact and reacted in parallel, ie. simultaneously, with starting material or starting material mixtures in liquid and/or gaseous form batchwise or continuously. Automation of the apparatus according to the invention is possible, in particular charging the reactors with catalysts can proceed automatically, preferably by a laboratory robot or a pipetting machine.
In a further preferred embodiment, the miniaturized reactors are designed in the metal block as 4 mm bore holes and disposed in such a manner that differing starting material and inert gases can flow through them through 2.5 mm capillary bore holes. The gases then pass into a spacer, preferably a distancing plate, which is mounted on the metal block and in which the bore holes of the metal block continue. The arrangement of metal block and spacer is provided with a customary cuvette bore hole in which the gases can be analyzed by spectroscopy. For this purpose, the bore hole is sealed at both ends with a transparent window. If infrared spectroscopy is to be used for analysis, use is preferably made of windows of 1-1-1 silicon, NaCl, KBr, Ge, ZnSe or KSR5. For the analysis, a collimated analytical beam, in the case of IR spectroscopy an infrared beam, is decoupled from an interferometer, preferably without a mirror, and directed through a dry-gas-flushed space through the cuvette bore hole onto a detector situated behind. The cuvette bore hole can be, for example, 5 mm thick. By choosing a suitable thick spacer, the length of the cuvette bore hole can be chosen between a few cm (1-10) and several 10 s of cm (10-50), depending on the reaction conditions and reaction type. To record the spectra, the analytical beam can be directed through all cuvette bore holes successively by a deflection apparatus. However, a plurality of beams or a plurality of analyzers can also be used, so that simultaneous recording of spectra is possible with a plurality of reactors. However, equally, the block containing the reactors can be moved by motion devices, for example stepper motors, in such a manner that all cuvette bore holes are brought successively into the beam path of the spectrometer. Suitable materials for block and spacer are preferably the customary corrosion-resistant metallic materials familiar to those skilled in the art, particularly aluminum or steel, preferably stable to rust and/or acid and/or high temperature.
A further embodiment of the apparatus according to the invention which is particularly suitable for homogeneous catalysis is characterized in that, in the case of at least one reactor having a volume which is preferably less than 200 xcexcl, an ATR crystal (attenuated total reflection spectroscopy, preferably conically pointed, preferably made of ZnSe or KSR5 or diamond) makes possible spectroscopic contact with the reaction mixture for differing solvents and reaction conditions and pressures up to 200 bar. In this case, the analytical beam is focused onto the ATR crystal.
The advantages of the process according to the invention and the apparatus according to the invention are essentially that a multiplicity of reactions can be carried out rapidly, inexpensively and reproducibly under virtually identical conditions and with comparatively small amounts of substance and sample and, in the course of this, can simultaneously be studied spectroscopically. It thus offers the opportunity of using the opportunities discussed in connection with combinatorial chemistry (K. Burgess et al., Ang. Chem. 1996, 108, 2, 192, incorporated by reference into the application) for industrial catalyst screening. By choosing identical samples and differing other reaction conditions such as temperature, pressure, starting material composition, a parallel reaction optimization can be carded out.
To analyze the data obtained, advantageously, a data matrix is prepared in such a manner that all selectable and documentable reaction conditions (starting material partial pressures, starting material composition, temperature, flow or flow rate, total pressure, sample composition, sample lattice parameters and all base points of the spectra) are given according to reaction conditions, ie. for each reactor, as columns of the matrix. This matrix can be subjected to a factor analysis (E. R. Malinowski et al., Factor Analysis in Chemistry, Wiley, New York, 1980, incorporated by reference into the application), by calculating the covariance matrix, the eigenvalues, the abstract eigenvectors, the loadings and the coefficients of the multidimensional regression, and preferably outputing them as files. A (pre)normalization of the data can also be selected by the mean xe2x80x9c0xe2x80x9d and standard deviations xe2x80x9c1xe2x80x9d, which can avoid base line effects or absolute effects. This permits the prediction of differing variables from calibration data sets (eg. quantitative CO2 contents at different temperatures), determination of the dependence of parameters in spectral ranges to optimization of the analysis, generation of different distance matrices from the output data (for example the similarity of catalysts with respect to selected variables and properties) and direct feedback of the catalyst composition to a laboratory robot synthesizer which mixes a set of new catalyst samples and synthesizes them xe2x80x9cautomaticallyxe2x80x9d by sintering or calcining on a robot line.
An embodiment of the process according to the invention and a development of the apparatus according to the invention are described in more detail below with reference to FIGS. 1 and 2, without the intention of restricting the invention in any manner.