Method for direct mechanocatalysis

Abstract

The invention relates to a method for direct mechanocatalysis, in which direct mechanocatalysis at least one starting material is reacted in the presence of a catalyst to form at least one end product, the method comprising or consisting of the following steps: (a) providing a vibration or resonant acoustic mixer, the reaction vessel of which is made of or coated with the catalyst suitable for the reaction to be carried out; (b) providing at least one starting material; (c) introducing the at least one starting material into the reaction vessel of the vibration or resonant acoustic mixer; and (d) carrying out the reaction.

Description

Processes for direct mechanocatalysis FIELD OF THE INVENTION

[0001] The invention is in the field of catalysis and relates to an improved process for direct mechanocatalysis, which does not require the use of grinding tools such as balls or rollers. TECHNOLOGICAL BACKGROUND

[0002] The term "mechanochemistry" refers to chemical reactions triggered by mechanical energy. Typically, chemical compounds are brought into reaction by impact or shear forces induced by the collision of grinding balls in vibrating or rotating grinding bowls. A review of this topic, entitled "Mechanochemical synthesis strategies," can be found by Friscic in the Encyclopedia of Inorganic and Bioinorganic Chemistry https: / / doi.org / 10.1002 / 9781119951438.eibc2202

[0003] In addition to energy transfer and reagent mixing, interaction of the grinding media with the reaction mixture is generally undesirable. For this reason, chemically inert grinding materials such as tungsten carbide (WC), steel, zirconium oxide (ZrO2), or polymers are used, and the grinding parameters are adjusted to suppress their abrasion.

[0004] There is also an opposing concept, in which the interaction of the grinding beads with the reagents is explicitly desired: so-called direct mechanocatalysis. Here, the grinding tools are the catalyst, which offers significant advantages in terms of catalyst separation and reusability. Grinding beads made of palladium, nickel, or copper have already been used for various reactions, particularly for the production of small molecules.

[0005] The use of catalysts in metal powder and / or metal salt form, however, presents several disadvantages compared to the use of milling materials made from the catalytically active metal or the metal coated with it. Firstly, the milling materials are almost infinitely reusable due to the lack of abrasion, whereas catalyst powders cannot be reused after the reactions. Thus, catalytically active milling materials have a reusability that is not available with catalyst powder. This significantly lowers the costs for individual reactions with catalytically active milling media (https: / / onlinelibrary.wiley.com / doi / full / 10.1002 / anie.2Q2212694). Another important advantage is product processing. Since catalyst powder is dispensed with and there is virtually no abrasion, complex separation of the Metals from the final product, this is of particular interest in pharmaceutical and fine chemical production.

[0006] An alternative to this technology is the use of vibration mixers (VM) and resonance acoustic mixers (RAM), which do not require grinding media. Resonance acoustic mixers were originally developed for mixing substances by introducing sound waves (US 7,188,993 RESODYN ACOUSTIC MIXERS). In recent years, it has been discovered that the process can also be applied to catalytic reactions, whereby the catalyst is traditionally added to the reaction mixture. In this process, pistons are set into vertical vibration at a low frequency in the acoustic range (approx. 60 Hz) and high amplitude. Vibration mixers were originally developed as drives for sieve shakers (EP 0642844, F. KURT RETSCH GmbH & Co. KG) and are characterized by a controlled electromagnetic drive and can also be controlled at various frequencies.In both devices, the entire system is maintained in a resonance state to ensure effective and energy-saving mixing. The main advantage of this method is that neither solvents nor grinding media are required. Since there is no metal abrasion and consequently no contamination of the reaction products, this process is of particular interest to the pharmaceutical, agricultural, and fine chemical industries. Furthermore, it is possible to operate vibration mixers and resonance-acoustic mixers continuously, thus overcoming another disadvantage of direct mechanocatalysis. Compared to ball or planetary mills, scaling is easily possible, which also enables industrial use. RELEVANT STATE OF THE ART

[0007] The production of chemicals by reacting the starting materials in a reaction vessel whose walls are coated with the catalyst is well known in the art. For example, reference is made to WO 2004 050587 A2 (BASF), which describes a process for producing hydrogen cyanide (HCN) by catalytic dehydration of gaseous formamide in a reactor having an inner reactor surface made of steel containing iron, chromium, and nickel.

[0008] A process for the direct mechano-catalyzed Suzuki reaction is known from the article "Galvanostatic Coating for Direct Mechanocatalysis" by Borchardt et al. It uses grinding media coated with different metals, with the top layer consisting of palladium. With regard to the lowest possible abrasion and simultaneously high conversions, grinding balls with the following sequence of coatings have proven particularly advantageous: First, copper (adhesion promoter), secondly nickel (diffusion barrier), thirdly gold (support layer) and finally palladium (catalyst) [Angew. Chemie Vol 134(47), e202212694 (2022)].

[0009] Examples of mechanochemical catalysis using RAM are known from the state of the art. For example, in their review "Metal-catalyzed organic reactions by Resonant Acoustic Mixing," Friscic et al. describe a ruthenium-catalyzed ring-closing metathesis and copper-catalyzed sulfonamide-isocyanate coupling reaction carried out in a Resodyn mixer [Angew. Chemie Vol. 134(13), e202115030 (2022)].

[0010] DE 1457142 A (SEUDIA) from 1969 describes a device for creating emulsions of liquids in gases by introducing sonic energy. The document states that the device is suitable for various chemical processes, such as hydrolysis, saponification, deodorization, purification processes, and the like. What they all have in common, however, is that they involve intimate mixing or emulsion formation. While the use of catalysts is not excluded, the reaction essentially occurs by bringing the reactants into contact.

[0011] JP 2003214600 A (JFE ENGINEERING) relates to a process for passing a fluid phase (liquid, gaseous, liquid / gaseous, possibly with solid components) through a porous body. The porous body can, for example, be a honeycomb mesh made of a platinum metal. TASK TO BE SOLVED

[0012] A disadvantage of using grinding balls made entirely of the catalytic metal in a direct mechanocatalysis process is their high material costs, especially for precious metals such as Pd. A more cost-effective method for providing the catalyst for this method is to simply coat the grinding media (balls, rollers, cups, etc.). However, at high frequencies and long reaction times, it is regularly observed that the coatings wear away. This is accompanied by a constant decrease in activity, a lack of reproducibility of the test results, limited recyclability of the grinding media, and contamination of the ground material with the abrasion. Scaling also proves difficult, as the problems described above steadily increase with the number and size of the grinding media.

[0013] Although catalysis in vibration and resonance acoustic mixers solves the problem of attrition and lack of scaling, the catalysts must be added in the traditional way and then separated from the product, which is a complex process.

[0014] The object of the present invention was therefore to modify the process for direct mechanocatalysis in such a way that the above-mentioned disadvantages are avoided. DESCRIPTION OF THE INVENTION

[0015] In a first embodiment, the invention relates to a process for direct mechanocatalysis, in which at least one starting material is converted in the presence of a catalyst to at least one end product, comprising or consisting of the following steps: (a) providing a vibration or resonance acoustic mixer, the reaction vessel of which consists of or is coated with the catalyst suitable for the reaction to be carried out; (b) providing at least one starting material; (c) introducing the at least one starting material into the reaction vessel of the vibration or resonance acoustic mixer and (d) Carry out the implementation.

[0016] Surprisingly, it was discovered that direct mechanocatalysis can be carried out without the disadvantages described if the abrasive grinding tools are dispensed with and the reaction mixtures are mixed in a resonance acoustic mixer. Carrying out the reactions with the introduction of acoustic energy under resonance conditions proves to be just as effective in terms of yield and reproducibility as mechanical mixing, in which the components are reacted by intimate contact between the grinding jar and the grinding tool, something that the person skilled in the art would not have expected. In vibration mixers, the substrate mixture is reacted by impact with the reaction vessel walls. The energy introduced by means of the angular momentum movement is sufficient for the reaction, something that the person skilled in the art would also not have expected.The process according to the invention avoids contamination of the reaction products with attrition, is easily scalable, and has a long service life. At the same time, complex catalyst separation is not required.

[0017] In contrast to classical catalyzed reactions, the process of the present invention surprisingly does not rely on achieving the greatest possible contact between catalyst and substrates. Rather, high conversions and yields are achieved despite small catalyst surface areas.

[0018] The following table lists typical reactions and the preferred metal catalysts for which the process according to the invention is particularly suitable, without limiting it to these: Preferably, at least one of the starting materials is a solid, particularly preferably the reaction is carried out exclusively among solids. Carrying out the process

[0019] In resonant acoustic or vibration mixing, as already described above, the starting materials are placed in a reaction or mixing vessel and then set in motion and mixed by introducing energy in the low frequency range of approximately 40 to approximately 80 Hz, and especially around 60 Hz at high amplitude, whereby the system is brought into resonance for constant mixing. A summary of the technology, its possible applications, and operating conditions can be found on the website of market leader Resodyn Inc. and can be accessed at https: / / resodynmixers.com / 2020 / 12 / 30 / what-is-resonantacoustic-mixing /

[0020] The reaction or mixing vessels are usually made of a chemically inert plastic or stainless steel. However, in the context of the present invention, it is intended that the The vessel itself represents or contains the catalyst. This catalyst can therefore be selected from the group of metals consisting of vanadium, molybdenum, iron, nickel, copper, palladium, iridium, platinum, rhodium, rhenium, ruthenium, and corresponding alloys. Alternatively, the catalyst can also be steel, in particular stainless steel, and optionally contains proportions of at least one metal selected from the group consisting of vanadium, molybdenum, nickel, copper, silver, gold, iridium, palladium, platinum, rhodium, rhenium, and / or ruthenium.

[0021] Thus, the reaction vessel can either consist entirely of the corresponding catalyst—or more specifically, the catalyst metal or catalyst alloy—and be simply coated with it, or contain it as a rigid body. As already mentioned at the beginning, solid catalysts are not required per se and a coating is more cost-effective. Such coated reaction vessels can consist not only of the actual vessel and the catalytically active coating; it can also be advantageous to have intermediate layers, such as the Cu / Ni / Au / Pd sequence.

[0022] The selection of the catalyst material depends exclusively on the reaction to be catalyzed and is therefore specific. However, once the skilled person knows which reaction requires which catalyst, they can select the reaction vessel with the correct catalyst without having to engage in inventive activity. The nature of the reaction to be carried out in the reaction vessel is largely uncritical. The skilled person will not select reactions that proceed without catalysis, nor reactions that proceed under conditions, such as high temperature or high pressure, for which neither resonance acoustic mixers nor vibration mixers are designed. The skilled person will also be able to make this decision without inventive activity.

[0023] The process is characterized by the fact that the use of grinding tools such as inert, coated or partially coated balls, rollers, needles, cylinders, and the like is generally not required. However, in individual cases, their use can be advantageous when achieving particularly high levels of mechanical mixing.

[0024] In many cases, the process requires no solvent at all. If solvents such as lower C1-C4 alcohols, especially ethanol, are used, then only in small amounts of approximately 0.1 to approximately 0.5 μl of solvent per mg of feedstock.

[0025] The process is characterized by the fact that the energy input is regulated by the acceleration of the resonance-based mixers, thus eliminating the need for external heating. The acceleration is set between 10 and 90 g, preferably between 40 and 90 g, and most preferably between 70 and 80 g. INDUSTRIAL APPLICABILITY

[0026] Another object of the invention relates to the use of vibration or resonance acoustic mixers, whose reaction vessels consist of a catalyst or are coated with a catalyst, in direct grinding media-free mechanocatalysis. EXAMPLES Example 1, Comparative Examples V1, V2 and V3 Preparation of diphenyl

[0027] The Suzuki coupling of phenylboronic acid and iodobenzene to biphenyl was investigated according to the following reaction equation, [Pd] = Pd coated RAM grinding bowl where the reaction was carried out: (a) in a resonance acoustic mixer from Resodyn ("LabRAM II"), with the reaction vessel coated with the Pd catalyst; (b) in a Retsch vibration mixer ("AS 200 BASIC"), with the reaction vessel coated with the Pd catalyst; (c) in a Retsch mixer mill (“MM500 Vario”) with Pd-coated grinding bowl and / or Pd-coated grinding balls; (d) after classical Pd-catalyzed synthesis in solvent.

[0028] The results are shown in Table 1 below. Example 1 is according to the invention; examples V1, V2, and V3 are for comparison. Table 1 Test results

[0029] The investigations show that the invention is distinguished from the comparative experiments in that an abrasion-free product is obtained with the same complete conversion, which can be easily scaled.

Claims

PATENT CLAIMS 1. A process for direct mechanocatalysis in which at least one starting material is converted in the presence of a catalyst to at least one end product, comprising or consisting of the following steps: (a) providing a vibration or resonance acoustic mixer, the reaction vessel of which consists of or is coated with the catalyst suitable for the reaction to be carried out; (b) providing at least one starting material; (c) introducing the at least one starting material into the reaction vessel of the vibration or resonance acoustic mixer and (d) Carry out the implementation.

2. Process according to claim 1, characterized in that at least one starting material is a solid.

3. Process according to claims 1 and / or 2, characterized in that the catalyst is selected from the group of metals formed by vanadium, molybdenum, iron, nickel, copper, palladium, iridium, platinum, rhodium, rhenium, ruthenium and corresponding alloys.

4. Process according to claims 1 and / or 2, characterized in that the catalyst is steel, in particular stainless steel, and optionally contains proportions of at least one metal selected from the group consisting of vanadium, molybdenum, nickel, copper, silver, gold, iridium, palladium, platinum, rhodium, rhenium and / or ruthenium.

5. Process according to at least one of claims 1 to 4, characterized in that no grinding tools, in particular no inert, coated or partially coated grinding balls or rollers, are used.

6. Process according to at least one of claims 1 to 5, characterized in that no or almost no solvents are used.

7. Process according to at least one of claims 1 to 6, characterized in that the reaction is carried out in the vibration or resonance acoustic mixer in a frequency range of about 40 to about 80 Hz under resonance conditions.

8. Process according to at least one of claims 1 to 7, characterized in that the reaction is carried out in a vibration or resonance acoustic mixer with an acceleration between 40 and 90 g. Use of vibration or resonance acoustic mixers, whose reaction vessels consist of a catalyst or are coated with a catalyst, in direct grinding media-free mechanocatalysis.

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