EP2488292A2

EP2488292A2 - Method for carrying out sequential reactions using a heating medium heated by means of induction

Info

Publication number: EP2488292A2
Application number: EP10730422A
Authority: EP
Inventors: Carsten Friese; Andreas Kirschning; Sascha Volkan Ceylan; Jens Wegner
Original assignee: Henkel AG and Co KGaA
Current assignee: Henkel AG and Co KGaA
Priority date: 2009-10-13
Filing date: 2010-06-29
Publication date: 2012-08-22
Also published as: US20120283449A1; WO2011045091A3; DE102009045636A1; CN102548649A; WO2011045091A2

Abstract

The invention relates to a method for carrying out at least two successive chemical reactions for producing a target compound from at least one first and at least one second and/or further reactants, comprising a first reaction and a further reaction in a reactor containing a reaction medium, wherein the reaction medium in the reactor is brought in contact with a solid heating medium that can be heated by means of electromagnetic induction and that is located inside the reactor and surrounded by the reaction medium. The heating medium is heated by means of electromagnetic induction using an inductor, wherein in a first reaction, an intermediate compound is formed, from which in a further reaction the target compound is generated. Between the first and the further reactions, at least one reactant that was not present in the reactor before the first reaction is added to the reactor. The target compound is separated from the heating medium.

Description

Henkel AG & Co. KGaA

H 08426 PCT

June 29, 2010

"Method of performing sequential reactions using an inductively heated

heating medium "

The present invention is in the field of chemical synthesis and relates to a method for carrying out sequential, ie sequential chemical reactions using an inductively heated heating medium.

For carrying out thermally inducible chemical reactions, different ways are known to heat the reactants. The most common is heating by heat conduction. In this case, the reactants are in a reactor, wherein either the walls of the reactor itself are heated or in which heat transferring elements such as heating coils or heat exchanger tubes or plates are installed in the reactor. This process is relatively slow, so that on the one hand the heating of the reactants takes place slowly and on the other hand, the heat supply can not be quickly prevented or even replaced by a cooling. An alternative to this is to heat the reactants by irradiating microwaves into the reactants themselves or into a medium containing the reactants. However, microwave generators represent a significant security risk because they are expensive in terms of apparatus and there is a risk of the emission of radiation.

In contrast, the present invention provides a method of heating a reaction medium by bringing it into contact with a heating medium heatable by electromagnetic induction, which is heated "externally" by electromagnetic induction by means of an inductor.

The process of inductive heating has been used in industry for some time. The most common applications are melting, hardening, sintering and the heat treatment of alloys. But also processes such as gluing, shrinking or joining of components are known applications of this heating technology. From the German patent application DE 198 00 294 methods for the isolation and analysis of biomolecules are known, wherein these biomolecules are bound to the surface of inductively heatable magnetic particles. This document explains:

"The mechanism of action is to adsorptively or covalently attach to the surface of a functional polymer matrix, in which the inductively heatable magnetic colloids or finely dispersed magnetic particles are encapsulated, biomolecules capable of measuring analytes, e.g. DNA / RNA sequences, antibodies, antigens, proteins, cells, bacteria, viruses or fungal spores to bind according to the complementary affinity principle. After the binding of the analytes to the matrix, the magnetic particles can be heated in a high-frequency alternating magnetic field to the relevant for the analysis, diagnosis and therapy temperatures of preferably 40 to 120 ° C. "Further, this document goes to the technical design of coil systems and This document thus describes the use of inductively heatable particles in the analysis of complex biological systems or biomolecules.

DE 10 2005 051637 describes a reactor system with a microstructured reactor and method for carrying out a chemical reaction in such a reactor. In this case, the reactor is heated as such by electromagnetic induction. The heat transfer into the reaction medium takes place via the heated reactor walls. This limits on the one hand the size of the area available for heating the reaction medium. On the other hand, it is necessary to heat parts of the reactor, which are not in direct contact with the reaction medium.

No. 5,10,996 describes the preparation of vinylidene fluoride by reacting dichloro difluoromethane with methane in the gas phase in a heated reactor. The reactor is filled with a non-metallic filler. The reaction space containing this filling material is surrounded by a metallic shell, which is heated from the outside by electromagnetic induction. The reaction space itself is therefore heated from the outside, as a result of which the filling material likewise heats up as a result of heat radiation and / or heat conduction over time. An immediate heating of the filling material flowed around by the reactants by electromagnetic induction does not take place even if this filling material is electrically conductive, since the metallic reactor wall shields the electromagnetic fields of the induction coil.

WO 95/21 126 discloses a process for the production of hydrogen cyanide in the gas phase from ammonia and a hydrocarbon by means of a metallic catalyst. The Ka The catalyst is located within the reaction space, so that it flows around in front of the reactants. It is heated externally by electromagnetic induction at a frequency of 0.5 to 30 MHz, ie with an alternating field in the high-frequency range. In this case, this document cites the aforementioned document US Pat. No. 5,110,996 with the remark that usually inductive heating is carried out in the frequency range from about 0.1 to 0.2 MHz. However, this specification is not included in the cited US Pat. No. 5,110,996 so that it is unclear to what it refers to.

WO 00/38831 deals with controlled adsorption and desorption processes wherein the temperature of the adsorbent material is controlled by electromagnetic induction,

From the journal article "Inductive Heating in Organic Synthesis ..." by S. Ceylan, C. Friese, Ch. Lammel, K. Mazac and A. Kirschning, Angew Chem 2008 (129), SS. 9083-9086, Angew Chem. Int. Ed. 2008 (47), pp. 8950-8953 it is known that chemical reactions can be carried out by heating a heating medium with the aid of electromagnetic induction Meanwhile, German patent application DE 102007059967 and international patent application WO 2009/074373 Some reactions are exemplified, but no sequential chemical reactions involving at least one intermediate compound upon addition of another reactant to form a target compound are included.

In a general embodiment, the present invention relates to a process for carrying out at least two successive chemical reactions for producing a target compound from at least one first and at least one second and / or another reactant, comprising a first reaction and a further reaction in a reactor containing a reaction medium, wherein the reaction medium in the reactor is brought into contact with a heatable by electromagnetic induction solid heating medium, which is located within the reactor and which is surrounded by the reaction medium, and the heating medium is heated by electromagnetic induction by means of an inductor in which, in a first reaction, an intermediate compound forms, from which the target compound is formed in a further reaction, and wherein between the first and the further reaction, at least one reactant is added to the reactor before the first reaction was not present in the reactor and wherein separating the target compound from the heating medium. For example, but not by way of limitation, the target compound may be formed by one of the following reaction sequences:

a) Within the first reactant, as a first reaction, an intramolecular bond rearrangement or fragmentation to an intermediate occurs which reacts with one or more second reactants in a further reaction to the target compound; b) the first reactant reacts in a first reaction with a second reactant to form an intermediate compound from which the target compound forms in a further reaction with another reactant;

c) the first reactant reacting in a first reaction with a second reactant to form a first intermediate compound from which a second intermediate compound forms in a second reaction by intramolecular bond rearrangement or fragmentation, from which in a further reaction with another reactant the target compound arises.

A "further reactant" thus means a reactant which reacts with an intermediate compound The first reaction and the further reaction can take place separately in the same reactor, after at least substantial formation of the intermediate compound (for example, close to the equilibrium state) added to further reactants to obtain in a further reaction of the intermediate compound, the target compound.

It may be appropriate to separate the first and the further reaction not only temporally, but also spatially, so to run in different reactors. As explained below, in this case preferably flow reactors arranged one behind the other are used. Therefore, a preferred embodiment of the present invention is a process for carrying out at least two consecutive chemical reactions to produce a target compound from at least a first and at least one second and / or further reactants, wherein the first reaction in a first reactor and the further reaction takes place in a second reactor, each containing a reaction medium, bringing the reaction medium in each reactor in contact with a heatable by electromagnetic induction solid heating medium, which is located within the reactor and which is surrounded by the reaction medium, and the heating medium by e - Electromagnetic induction heated by means of an inductor, wherein adding at least one reactant in the second reactor, which was not present in the first reactor.

In each case additional reaction steps are not excluded. The term "target compound" is understood as meaning the compound which is obtained as the result of the process according to the invention as an isolated substance, as a component of a substance mixture or as a solution in a solvent in macroscopic amounts In contrast, the intermediate compound is not isolated as such but is reacted in one or more further reaction steps to the target compound However, an intermediate is superior to a "transition state" of a chemical reaction in that it is stable enough is to be isolated or at least by spectroscopic methods (eg IR or Raman spectrum, UV / vis spectrum, NMR or ESR spectrum) to be detected.

The chemical reactions are thus started by heating a reaction medium and optionally maintained, which contains the respective reactants. This includes the possibility that the reaction medium, for example a liquid, itself participates in the reaction and thus constitutes a reactant. In this case, a reactant may be dissolved or dispersed in the reaction medium, wherein the reaction medium itself may be inert or in turn may constitute a reactant. Or one, two or more reactants are dissolved or dispersed in a reaction medium which itself is not altered by the chemical reactions.

The solid heating medium is surrounded by the reaction medium. This may mean that the solid heating medium, apart from possible edge zones, is located within the reaction medium, e.g. if the heating medium in the form of particles, chips, wires, nets, wool, packing, etc. is present. However, this can also mean that the reaction medium flows through the heating medium through a plurality of cavities in the heating medium, if this consists for example of one or more membranes, a bundle of tubes, a rolled metal foil, frits, porous packing or of a foam. Again, the heating medium is essentially surrounded by the reaction medium, since most of its surface (90% or more) is in contact with the reaction medium. In contrast, in a reactor whose outer wall is heated by electromagnetic induction (such as in the cited document US 51 10996), only the inner reactor surface is in contact with the reaction medium.

The wall of the reactor is made of a material that does not shield or absorb the alternating electromagnetic field generated by the inductor and therefore does not heat itself. Metals are therefore unsuitable. For example, it may be made of plastic, glass or ceramics (such as For example, silicon carbide or silicon nitride) exist. The latter is particularly suitable for reactions at high temperature (500-600 ° C) and / or under pressure. A special reactor material that can also be used for reactions under moderate pressure (up to about 10 bar) is polyetheretherketone (PEEK).

The procedure described above has the advantage that the thermal energy for triggering and / or carrying out the chemical reactions is not introduced into the reaction medium by surfaces such as the reactor walls, heating coils, heat exchanger plates or the like, but is produced directly in the volume of the reactor. The ratio of the heated surface to the volume of the reaction medium can be substantially greater than in the case of heating via heat-transferring surfaces, as is also the case, for example, according to DE 10 2005 051637 cited at the outset. In addition, the efficiency of electric power is improved to heat output. By switching on the inductor, the heat can be generated in the entire solid heating medium, which is in contact with the reaction medium over a very large surface area. When switching off the inductor, the further heat input is prevented very quickly. This allows a very targeted reaction.

After formation of the target compound, this is separated from the heating medium. In the best case, the target compound in pure form, ie without solvent (which can be separated by distilling off the solvent or by precipitating the target compound from the solvent) and isolated with no more than the usual impurities. However, the target compound can also be separated from the heating medium in a mixture with reactants or as a solution in the reaction medium and only then isolated by further work-up or transferred to another solvent, if desired. The process thus serves for the preparative preparation of the target compound in order to be able to continue to use it.

In contrast, there are methods in which although a chemical reaction is initiated by electromagnetic induction of a heating medium, but this reaction is not used to produce a target compound, which is separated from the heating medium after the reaction. An example of this is hardening of resin systems wherein the curing reaction is started on particles dispersed in the resin system which are heated by electromagnetic induction. In the process, these particles remain in the cured resin system and no defined target compound is isolated. The same applies to the reverse case that an adhesive bond is released by the inductive heating of particles, which are located in the adhesive matrix. Although a chemical reaction can take place, no target compounds are isolated.

The heating medium consists of an electrically conductive and / or magnetizable material that heats up when exposed to an alternating electromagnetic field. It is preferably selected from materials which have a very large surface area compared to their volume. For example, the heating medium may be selected from in each case electrically conductive chips, wires, nets, wool, membranes, porous frits, tube bundles (of three or more tubes), rolled metal foil, foams, random packings such as granules or spheres, Raschig rings and in particular Particles preferably having a mean diameter of not more than 1 mm. For example, can be used as a heating medium metallic mixing elements, as used for static mixer. In order to be heatable by electromagnetic induction, the heating medium is electrically conductive, for example metallic (which may be diamagnetic), or exhibits a diamagnetism-enhanced interaction with a magnetic field and is especially ferromagnetic, ferrimagnetic, paramagnetic or superparamagnetic. It is irrelevant whether the heating medium of organic or inorganic nature or whether it contains both inorganic and organic components.

In a preferred embodiment, the heating medium is selected from particles of electrically conductive and / or magnetizable solids, wherein the particles have an average particle size in the range from 1 to 1000, in particular from 10 to 500 nm. The average particle size and, if necessary, the particle size distribution can be determined, for example, by light scattering. Magnetic particles, for example ferromagnetic or superparamagnetic particles, which have the lowest possible remanence or residual magnetization, are preferably selected. This has the advantage that the particles do not adhere to each other. The magnetic particles may, for example, be in the form of so-called "ferrofluids", ie liquids in which ferromagnetic particles are dispersed on the nanoscale scale The liquid phase of the ferrofluid may then serve as the reaction medium.

Magnetisable particles, in particular ferromagnetic particles, which have the desired properties are known in the art and are commercially available. For example, the commercially available ferrofluids may be mentioned. Examples of the preparation of magnetic nano-particles which can be used in the context of the method according to the invention can be found in the article by Lu, Salabas and Schüth: "Magnetic nano-particles: Synthesis, Stabilization, Functionalization and Application ", Angew. Chem. 2007, 19, pages 1242 to 1266.

Suitable magnetic nano-particles are known with different compositions and phases. Examples include: pure metals such as Fe, Co and Ni, oxides such as Fe ₃ 0 ₄ and gamma Fe ₂ 0 ₃ , spinel-like ferromagnets such as MgFe ₂ 0 ₄ , MnFe ₂ 0 ₄ and CoFe ₂ 0 ₄ and alloys such as CoPt ₃ and FePt. The magnetic nanoparticles can be homogeneously structured or have a core-shell structure. In the latter case, core and shell may consist of different ferromagnetic or antiferromagnetic materials. However, embodiments are also possible in which at least one magnetizable core, which can be, for example, ferromagnetic, antiferromagnetic, paramagnetic or superparamagnetic, is surrounded by a nonmagnetic material. This material may be, for example, an organic polymer. Or the shell is made of an inorganic material such as silica or Si0. ₂ By means of such a coating, a chemical interaction of the reaction medium or of the reactants with the material of the magnetic particles themselves can be prevented. Furthermore, the material of the shell can be surface-functionalized without the material of the magnetizable nucleus interacting with the functionalizing species. In this case, also several particles of the core material can be enclosed together in such a shell.

As a heating medium, for example, nanoscale particles of superparamagnetic materials can be used, which are selected from aluminum, cobalt, iron, nickel or their alloys, metal oxides of the n-maghemite type (gamma-Fe ₂ 0 ₃ ), n-magnetite (Fe ₃ 0 ₄ ) or ferrites of the MeFe ₂ O _{4 type} , where Me is a divalent metal selected from manganese, copper, zinc, cobalt, nickel, magnesium, calcium or cadmium. Preferably, these particles have an average particle size of <100 nm, preferably <= 51 nm and particularly preferably <30 nm.

For example, a material which is available from Evonik (formerly Degussa) under the name MagSilica ^R is suitable. In this material, iron oxide crystals having a size of 5 to 30 nm are embedded in an amorphous silica matrix. Particularly suitable are those iron oxide-silica composite particles, which are described in detail in the German patent application DE 101 40 089.

These particles may contain superparamagnetic iron oxide domains with a diameter of 3 to 20 nm. These include spatially separated superparamagnetic To understand areas. In these domains, the iron oxide may be present in a uniform modification or in various modifications. A particularly preferred superparamagnetic iron oxide domain is gamma Fe ₂ O ₃ , Fe ₃ O ₄ and mixtures thereof.

The proportion of the superparamagnetic iron oxide domains of these particles can be between 1 and 99.6 wt .-%. The individual domains are separated and / or surrounded by a nonmagnetizable silicon dioxide matrix. The range with a proportion of superparamagnetic domains of> 30 wt .-%, particularly preferably> 50 wt .-% is preferred. The proportion of superparamagnetic regions also increases the achievable magnetic activity of the particles according to the invention. In addition to the spatial separation of the superparamagnetic iron oxide domains, the silica matrix also has the task of stabilizing the oxidation state of the domain. For example, magnetite is stabilized as a superparamagnetic iron oxide phase by a silica matrix. These and other properties of these particles which are particularly suitable for the present invention are described in greater detail in DE 101 40 089 and in WO 03/042315.

Furthermore, nano-scale ferrites can be used as heating medium, as they are known for example from WO 03/054102. These ferrites have a composition (M ^a _1-xy M ^b _x Fe " _y ) Fe"' ₂ 0 ₄ , in which

M ^{a is} selected from Mn, Co, Ni, Mg, Ca, Cu, Zn, Y and V

M ^{b is} selected from Zn and Cd,

x is 0.05 to 0.95, preferably 0.01 to 0.8,

y stands for 0 to 0.95 and

the sum of x and y is at most 1.

It can be provided that the solid heating medium is superficially occupied by a catalytically active substance for at least one of the chemical reactions. Carrying out the reactions, as described below, in a flow reactor, so you can provide different heating media in the flow reactor in a row. These may be occupied by different catalytically active substances that are specific for each of the first or another chemical reaction.

The process according to the invention is particularly suitable for carrying out thermally inducible reactions. A general limitation of the possible types of reactions does not exist, unless reaction conditions (such as pH) are selected or Used educts or products are formed, which destroy the heating medium. By way of example, it is possible to carry out sequences of chemical reactions in which at least one chemical bond between 2 C atoms or between a C atom and an X atom is formed, cleaved or rearranged in at least one of the chemical reactions, where X can, for example, be selected from: H , B, O, N, S, P, Si, Ge, Sn, Pb, As, Sb, Bi and halogens. This can also be a rearrangement of chemical bonds, as occurs for example in cycloadditions and Diels-Alder reactions. However, bonds between two identical or different atoms X can also be formed and / or dissolved, where X can have the abovementioned meaning. In general, a "formation of a bond" is understood as meaning a transformation of a single bond into a double bond or of a single or double bond into a triple bond, etc. The reverse process is covered by the term "releasing a bond".

For example, the thermally inducible reaction may correspond to at least one of the following reaction types: oxidation (including dehydrogenation), reduction (including hydrogenation), fragmentation, addition to a double or triple bond (including cycloaddition and Diels-Alder reaction), substitution ( SN1 or SN2, radical), in particular aromatic substitution, elimination, rearrangement, cross-coupling, metathesis reaction, formation of heterocycles, ether formation, ester formation or transesterification, amine or amide formation, urethane formation, pericyclic reaction, Michael addition, condensation, polymerization ( free radical, anionic, cationic), grafting of polymers. ( "Polymer-grafting").

For reduction or hydrogenation reactions, suitable reducing agents or sources of hydrogen are, for example: cycloalkenes such as cyclohexene, alcohols such as ethanol, inorganic hydrogenating reagents such as sodium borohydride or sodium aluminum hydride.

At least one of the sequential chemical reactions can represent, for example, an oxidation reaction. For this, the following possible embodiments apply:

An embodiment of the method according to the invention, including an oxidation reaction, is characterized in that the particles of electrically conductive and / or magnetizable solids contain at least partially oxidic groups and serve as oxygen carriers for the oxidation reaction. For example, magnetizable metal oxides having an oxidizing effect with respect to the first reactant can be used. In this case, therefore, the heating medium itself represents the oxidizing agent (oxygen carrier). Example here- are inductively heatable oxides such as the above-mentioned ferrites of the type of Me-Fe ₂ 0 ₄ or (M ^a _1-xy M ^b _x Fe " _y ) Fe '" ₂ 0 ₄ , gamma-Fe ₂ 0 ₃ , Fe ₃ 0 ₄ and mixtures thereof.

An alternative embodiment is characterized in that the heating medium is selected from particles of magnetizable solid and that they are present in admixture with further particles which at least partially contain oxidic groups and serve as oxygen carriers for the oxidation reaction. These further particles themselves need not be directly heatable by electromagnetic induction. Rather, they are heated and activated by direct (particle-particle contact) or indirect (through the intermediary of the reaction medium) heat transfer from the heatable particles. For this purpose, for example, oxides of semimetals and metals are suitable, which can have several positive oxidation states, if in the oxides, the metal or metalloid is present in a higher than the smallest possible positive oxidation state. Examples are: oxides of Ce (IV), Pb (IV), Sb (V), V (V), Cr (IV and higher), Mn (IV and higher), Fe (III), Co (III or IV) and Cu (II). Metal peroxides are also suitable, for example selenium peroxide or nickel peroxide, in particular in the form of nanoparticles with an average particle size below 100 determined by light scattering methods.

In both alternatives, as the oxidation reaction progresses, the particles deplete of oxidic groups, so that the reaction would soon come to a standstill. Therefore, it is preferably provided that the particles which at least partially contain oxidic groups and serve as oxygen carriers for the oxidation reaction are provided again with oxidic groups during or after the oxidation reaction by reaction with oxygen. This means that either oxygen or an oxygen carrier is continuously introduced into the reactor, so that the oxide groups of the particles are immediately regenerated (so that the particles act in a similar way to a catalyst), or the particles are regenerated in batches by one-off or multiple but discontinuous addition of oxygen or an oxygen transfer agent into the reactor. Examples of oxygen transfer agents are organic peroxides or organic peracids or their anions, inorganic peracids such as peroxo-sulfuric acid or peroxodisulfuric or their anions, oxo acids of halogens or their anions such as chlorates or perchlorates, or H ₂ 0 ₂ or compounds which can split off H ₂ 0 ₂ .

Another embodiment of the present invention including an oxidation reaction is that the reactor does not contain particles which at least partially contain oxidic groups but that the reaction medium itself contains oxygen. This can be achieved, for example, by reacting the oxygen in dissolved form and / or in Form as fine as possible gas bubbles (for example, by feeding through a frit) in the reaction medium brings. Preferably, this is done continuously, so that a continuous reaction is possible. The introduction of oxygen can also be carried out batchwise. In this embodiment, it may be advantageous to carry out the oxidation reaction under pressure. Therefore, a variant of this embodiment is that the reactor is designed as a pressure reactor and the chemical reaction at a pressure of above atmospheric pressure, preferably at least 1, 5 bar is performed. Higher pressures than 20 bar may not be required in practice, but are not excluded.

If "oxygen" is mentioned in the context of this invention, it may mean pure oxygen or an oxygen-containing gas, in the simplest case air.

As the oxidizing agent (oxygen carrier), however, can also serve another reactant, which in turn is reduced in the oxidation reaction. Examples of oxygen transfer agents are also for this embodiment: organic peroxides or organic peracids or their anions, inorganic peracids such as peroxo-sulfuric acid or peroxodisulfuric acid or their anions, oxo acids of halogens or their anions such as chlorates or Perchlorates, or H ₂ 0 ₂ or compounds that can split off H ₂ 0 ₂ .

A further embodiment of the method according to the invention is characterized in that the solid heating medium is superficially occupied by a substance catalytically active for the oxidation reaction. For example, this may be a layer of oxides of metals that readily change their oxidation states upon absorption and release of oxygen. For this purpose, for example, the metal oxides mentioned above come into consideration. These can be fixed on a polar silica gel layer which envelops inductively heatable metal compounds, as is the case, for example, with the MagSilica ™ heating material mentioned above. Or else one equips the heating material superficially with ion exchange groups such as -SO ^{3 "}

or -NR ₃ ⁺ from which can bind via ion exchange cations or anions with oxidizing properties, for example Ru0 ₄ ^" , Os04 ^2" , Mn0 ₄ ^" , I0 ₄ ^" , CI0 ₄ ^" , CI0 ₂ ^" , CIO ^" Metal oxides, cations or anions can act stoichiometrically as oxidizing agents and act as catalysts if, after their reduction by oxygen or oxygen transfer agents in the reaction medium, they are converted back into their oxidized form so that they are available again as an oxidizing agent. Further examples of oxidizing agents are the Dess-Martin periodinan or tetramethylpyridinium oxide. If these are provided with -OH groups, they can be fixed, if appropriate via a linker, to polar supports such as, for example, the silica gel layer of MagSilica ™. The molecular formulas of these compounds are:

A further embodiment of the method according to the invention is characterized in that in at least one of the chemical reactions, a metal-carbon bond is formed or split. Here, an organometallic compound (i.e., the compound containing a metal-carbon bond) may be a starting material, an intermediate or the target compound. The metal to which a carbon atom is bound or bound may be one of the metals typical for organometallic reactions. Examples include: Li, Mg, Al, Sn, Pb, Fe, Co, Ni, Zn, Na, K, B, Si, Cr, Cu, Ce or another metal

According to this embodiment of the process according to the invention, one of the following reactions can be carried out, for example, as a first or second reaction, but the invention is not restricted to these:

a) formation of metal alkyls such as alkylmagnesium compounds by reacting elemental metals with alkyl halides, including a reformate kinetics reaction,

b) metalation of aromatics by reaction with metal alkyls, for example the lithiation of benzene with alkyllithium (for example butyllithium),

c) formation of organometallic compounds by transmetalation

2 equivalents of Na d) formation of organometallic compounds by metal-halogen exchange.

2 equivalents of ieri-BuLi

R-L R-Li e) Formation of metal alkynes such as, for example, alkynylcopper compounds by reacting elemental metals with alkynes, if appropriate in the presence of a base (for example triethylamine).

f) addition reactions of metal H, metal C or metal ¹ metal ² (eg R ₃ Si metal) to alkenes and alkynes (hydrometalation, carbometalation, metallometalation).

g) formation of metal-arene complexes such as tricarbonyl (/? 6 - benzene) chromium (O) from benzene and chromium hexacarbonyl.

h) Reaction of organometallic compounds with electrophiles to form C-C bonds.

Furthermore, one of the chemical reactions may represent fragmentation. This means that either an intermediate compound or the target compound has a lower molecular weight than the starting compound and that for their preparation from the starting compound at least one covalent bond of the starting compound is cleaved. The covalent bond to be cleaved may in particular be a C-C bond, a C-O bond, a C-N bond, a C-Se bond or a C-S bond.

For example, one of the reactions may belong to the following group of reactions, but the invention is not limited to these.

a) Pyrolysis of oils

b) depolymerization reactions, for example the cleavage of polyolefins or of cyanoacrylate polymers or oligomers into smaller fragments or monomers, c) retrocycloadditions (such as retro-Diels-Alder reactions),

d) coarse ^'sche fragmentation (in its general form):

Again, the following discussion is general and does not require that any of the chemical reactions be any of the above reactions. However, they also apply to these reactions. Regardless of whether or not one of the chemical reactions involves reaction with oxygen, hydrogen or other gas, it may be provided to perform at least one of the reactions under pressure. Therefore, an embodiment of the method according to the invention is generally that at least one of the reactors is designed as a pressure reactor and at least one of the chemical reactions at a pressure of above atmospheric pressure, preferably of at least 1, 5 bar is performed. Higher pressures than 20 bar may not be required in practice, but are not excluded.

In principle, the process according to the invention can be carried out continuously or batchwise. If it is carried out batchwise, the procedure is preferably to move the reaction medium and the inductively heated solid heating medium relative to one another during the reaction. When using a particulate heating medium, this can be done in particular by stirring the reaction medium together with the heating medium or swirling the heating medium in the reaction medium. If, for example, nets or wool are used in a filament-shaped heating medium, it is possible, for example, to shake the reaction vessel containing the reaction medium and the heating medium.

A preferred embodiment of a batch reaction is that the reaction medium is together with particles of the heating medium in a reaction vessel and is moved by means of a moving member located in the reaction medium, wherein the moving element is arranged as an inductor through which the particles of the heating medium by electromagnetic Induction heated. In this embodiment, therefore, the inductor is located within the reaction medium. The movement element can be designed, for example, as a stirrer or as a piston moving up and down.

In addition, it can be provided that the reactor is cooled from the outside during the chemical reaction. This is particularly possible in batch operation when, as indicated above, the inductor is immersed in the reaction medium. The feeding of the alternating electromagnetic field into the reactor is then not hindered by the cooling device.

A cooling of the reactor can be done from the inside via cooling coils or heat exchangers or preferably from the outside. For cooling, it is possible to use, for example, optionally precooled water or else a cooling mixture whose temperature is below 0 ° C. Examples of such cooling mixtures are ice-salt mixtures, methanol / dry ice or liquid nitrogen. By cooling, a temperature gradient between the reactor wall and the inductively heated heating medium can be produced. This is particularly pronounced when using a cooling mixture with a temperature well below 0 ° C, such as methanol / dry ice or liquid nitrogen. The reaction medium, which is warmed up by the inductively heated heating medium, is then cooled externally again. The chemical reaction of the reactant then takes place only when it has contact with the heating medium or is at least in its immediate vicinity. Due to the relative movement of the reaction medium to the heating medium, product species formed during the reaction rapidly reach cooler areas of the reaction medium, so that their thermal further reaction is inhibited. In this way one can kinetically select a desired pathway for several possible reaction pathways of the reactant or reactants.

In this batch procedure, first a first chemical reaction may be carried out to form an intermediate compound before adding one or more further reactants with which or which the resulting intermediate reacts to the target compound.

In an alternative embodiment, the chemical reactions are carried out continuously in successively arranged flow reactors, wherein each flow reactor is at least partially filled with the solid heating medium and thereby at least one heatable by electromagnetic induction heating zone, wherein the reaction medium flows through the flow reactor continuously and wherein the inductor located outside the reactor. In this case, the reaction medium flows around the heating medium, e.g. if this is in the form of particles, chips, wires, nets, wool, packing etc. Or the reaction medium flows through the heating medium through a plurality of cavities in the heating medium, if this consists for example of one or more membranes, frits, porous packing or of a foam.

Preferably, each flow reactor is designed as a tubular reactor. In this case, the inductor may completely or at least partially surround the reactor. The alternating electromagnetic field generated by the inductor is then introduced into the reactor on all sides or at least from several points.

As used herein, "continuous" is understood to mean a reaction procedure in which the reaction medium flows through the reactor for at least such a period of time that a total volume of reaction medium which is large in comparison to the internal volume of the reaction mixture. The reactor itself flows through the reactor before it interrupts the flow of the reaction medium. "Large" in this sense means "at least twice as large". Of course, such a continuous reaction has a beginning and an end.

The heating medium can be the same in both reactors. Depending on the reaction type and requirements for the reaction, the heating media in the two reactors may also be different. Analogously, the inductors for both reactors can be identical or different and can be operated at the same or different powers. Accordingly, the temperatures in the two reactors may be the same or different. Ideally, the reaction conditions in the two reactors are coordinated so that the product of the first reaction in the first reactor quantitatively passes from the first reactor into the second reactor, so that it is available in the second reactor for a further reaction.

In this case, the two reactors can be separated from one another by a connecting element, through which the reaction medium flows from the first into the second reactor. However, the two reactors can also merge directly into each other, wherein the boundary between the first and the second reactor is defined by the fact that change the reaction conditions (temperature, type of heating medium, catalyst, addition of another reactant). For example, different heating zones can be heated to different degrees, resulting in a "first reactor" and a "second reactor". This can be done either by the arrangement of different heating media in the flow reactor or by differently designed inductors along the reactor. Thereby, different heating conditions can be set for the formation of the interconnection and the target compound.

If desired, a cooling zone may be provided after the (last) heating zone, for example in the form of a cooling jacket around the reactor.

Furthermore, it can be provided that the reaction medium after leaving the heating zone of the second reactor is brought into contact with an absorber substance which removes by-products or impurities from the reaction medium. For example, this may be a molecular sieve which is flowed through by the reaction medium after leaving the heating zone. As a result, a product purification is possible immediately after its production. Depending on the rate of the chemical reaction, the product yield may be increased by recycling the reaction medium, after flowing through the solid heating medium in one of the reactors, at least partially to re-flow the solid heating medium into this reactor. In this case, it can be provided after the respective passage of the solid heating medium that impurities, by-products or even the desired main product are removed from the reaction medium. For this purpose, the known different separation methods are suitable, for example absorption on an absorber substance, separation by a membrane process, precipitation by cooling or distillative separation. As a result, a complete conversion of the reactant or reactants can ultimately be achieved.

The expediently to be selected total contact time of the reaction medium with the respective inductively heated heating medium depends on the kinetics of the respective chemical reaction. The slower the desired chemical reaction, the longer the contact time is. This can be adapted empirically in individual cases and can be done by tuning the flow rate, the free (ie not occupied by the heating medium) reactor diameter and the reactor length for each reactor. As an indication, it may be considered that preferably the reaction medium flows through the flow reactor once or several times at such a rate that the total contact time of the reaction medium with the inductively heated heating medium in each reactor is in the range from about 1 second to about 2 hours before the target compound separates. Shorter contact times are conceivable but more difficult to control. Longer contact times may be required for particularly slow chemical reactions, but they are increasingly degrading the economics of the process.

Preferably, the process according to the invention is carried out in such a way that the reaction medium in the respective reactor is present under the set reaction conditions (in particular temperature and pressure) as a liquid. As a result, based on the reactor volume, generally better volume / time yields are possible than in the case of reactions in the gas phase.

It goes without saying that the nature of the heating media and the design of the inductors must be adapted to each other so that the desired heating of the reaction medium can be realized. One critical factor for this is the power of the inductor, which can be expressed in watts, as well as the frequency of the alternating field generated by the inductor. In principle, the power must be chosen higher, the greater the mass of the inductively warming medium is. In practice, the achievable power is limited in particular by the possibility of cooling the generator required to supply the inductor.

Particularly suitable are inductors which generate an alternating field with a frequency in the range from about 1 to about 100 kHz, preferably from 10 to 80 kHz and in particular in the range from about 10 to about 50 kHz, especially up to 30 kHz. Such inductors and the associated generators are commercially available, for example from IFF GmbH in Ismaning (Germany).

Thus, inductive heating is preferably carried out with an alternating field in the middle frequency range. Compared to an excitation with higher frequencies, for example those in the high-frequency range (frequencies above 0.5, in particular above 1 MHz), this has the advantage that the energy input into the heating medium is better controllable. This is especially true when the reaction medium is present under the reaction conditions as a liquid. Therefore, in the context of the present invention it is preferred that the reaction medium is present as a liquid and that inductors are used which produce an alternating field in the abovementioned medium-frequency range. This allows an economical and easily controllable reaction.

As a heating medium can be used, for example: a) MagSilica ^® 58/85 from Evonik (formerly Degussa)

b) manganese ferrite powder,

c) Bayferrox ^® 318 M: synthetic alpha-Fe ₃ 0 ₄ & Harold Scholz Co. GmbH, d) Manganese-zinc ferrite surface-coated with oleic acid, ferrite 51, 7 wt .-%, e) balls or other shaped articles, Rolled sheets, shavings, rolled up nets or wool of metal.

f) Fe ₂ 0 ₃ , in particular in the form of nanoparticles having a particle size in the range of 20 to 200 nm or Fe ₃ 0 ₄ , in particular in the form of nanoparticles having a particle size in the range of 20 to 200 nm (each available from DKSH GmbH , Germany), g) steel balls, for example ball bearing balls, preferably with a diameter of at most 1 mm, for example between 0.5 and 1 mm

In a specific embodiment of the method according to the invention, the heating medium is ferromagnetic and has a Curie temperature in the range of about 40 to about 250 ° C, which is selected so that the Curie temperature by not more than 20 ° C, preferably not more than 10 ° C from the selected reaction temperature. This leads to inherent protection against accidental overheating. The heating medium can be heated by electromagnetic induction only up to its Curie temperature, while it is not further heated by the electromagnetic alternating field at an overlying temperature. Even with a malfunction of the inductor can be prevented in this way that the temperature of the reaction medium unintentionally increases to a value well above the Curie temperature of the heating medium. If the temperature of the heating medium falls below its Curie temperature again, it can be heated again by electromagnetic induction. This leads to a self-regulation of the temperature of the heating medium in the range of the Curie temperature.

As tubular reactors, for example, glass tubes or PEEK reactors of 10 to 20 cm in length, for example, 12 cm in length, and different inner and outer diameter can be used. At both ends, the pipes can be provided with screw connections in order to be able to attach HPLC connections and the appropriate hoses.

A suitable inductor has the following characteristics: Inductance: 134 μΗβηΓν, number of turns of the coil: = 2 ^■ 16, cross-sectional area = 2.8 mm ² (The cross-sectional area results from the number of conductor wires used in the inductor and their diameter Gaps for receiving the tubular reactors can be 12 mm. The inductor is operated, for example, at a frequency of 25 kHz.

Embodiment:

Reaction I

(Suzuki reaction)

2 7 bar 3

Reaction II

(Wittig reaction)

7 bar 5 A PEEK reactor (12 cm long, 8.5 mm internal diameter) is filled with MagSilica and a palladium-on-carbon catalyst and finished with cotton wool on both sides. One end of the reactor is connected to an HPLC pump, the other end is connected via a T-mixer and a pressure valve (7 bar) to a second PEEK reactor (12 cm long, 8.5 mm internal diameter). The second inlet of the T-mixer is connected to a second HPLC pump. The second PEEK reactor is filled with MagSilica ™. The other end of the PEEK reactor is connected to a pressure valve (7 bar), which ends in a collecting vessel. Both reactors are used in inductors and the entire system is rinsed with ethanol. At both inductors, a temperature of 100 ° C is set (excitation frequency in each case 250 parts per thousand). A flow rate of 0.1 mL / min is set on both HPLC pumps. After a constant flow rate and temperature have been established, the first HPLC pump is used to pump a solution of aryl bromide 1, boronic acid 2, and cesium fluoride in ethanol (5 mL) through the system. Via the second HPLC pump, a solution of Wittig reagent 4 in ethanol is introduced into the T-mixer. There, the reaction solution mixes with the product 3 of the first reaction and is reacted in the second reactor. Subsequently, another 15 mL of ethanol are pumped through the system via the first HPLC pump and 15 mL of ethanol through the second HPLC pump. The combined organic phases are concentrated in vacuo and the residue washed several times with water. The aqueous phase is extracted twice with ethyl acetate and the combined organic phases dried over MgS0 ₄ . After concentrating the organic phase, the residue is purified by column chromatography (SiO ₂ , ethyl acetate / petroleum ether 50: 1) and the target compound 5 is obtained in a yield of 80%.

Claims

claims

1 . A process for carrying out at least two consecutive chemical reactions to produce a target compound from at least one first and at least one second and / or another reactant, comprising a first reaction and a further reaction in a reactor containing a reaction medium, wherein the reaction medium in the reactor in contact with a heatable by electromagnetic induction solid heating medium, which is located within the reactor and which is surrounded by the reaction medium, and the heating medium is heated by electromagnetic induction by means of an inductor, wherein in a first reaction, an intermediate compound forms from which, in a further reaction, the target compound is formed, and wherein between the first and the further reaction, at least one reactant is added to the reactor which was not present in the reactor before the first reaction, and wherein the target compound from the heating medium a btrennt.

2. The method of claim 1, whereby the target compound is formed by one of the following reaction sequences:

a) Within the first reactant, as a first reaction, intramolecular bond rearrangement or fragmentation takes place to an intermediate which reacts with one or more second reactants in a further reaction to the target compound;

b) the first reactant reacts in a first reaction with a second reactant to form an intermediate compound from which the target compound forms in a further reaction with another reactant;

3. The method according to any one of claims 1 and 2, wherein the first reaction takes place in a first reactor and the further reaction in a second reactor, each containing a reaction medium, wherein the reaction medium in each reactor in contact with a heatable by electromagnetic induction solid heating medium which is located inside the reactor and which is surrounded by the reaction medium and the heating medium is heated by electromagnetic induction by means of an inductor, wherein at least one reactant is added to the second reactor which was not present in the first reactor.

4. The method according to one or more of claims 1 to 3, characterized in that the heating medium is selected from particles of electrically conductive and / or magnetizable solid, wherein the particles have an average particle size in the range of 1 to 1000 nm.

5. The method according to one or more of claims 1 to 4, characterized in that the heating medium is selected from particles of electrically conductive and / or magnetizable solid, each particle contains at least one core of an electrically conductive and / or magnetizable material, which is enveloped by a non-magnetic material.

6. The method according to at least one of claims 1 to 5, characterized in that at least one reactor is designed as a pressure reactor and at least one of the chemical reactions at a pressure of above atmospheric pressure, preferably of at least 1, 5 bar is performed.

7. The method according to one or more of claims 1 to 6, characterized in that at least one solid heating medium is superficially occupied with a catalytically active substance for at least one of the chemical reactions.

8. The method according to one or more of claims 1 to 7, characterized in that one carries out the chemical reactions each in a flow reactor, which is at least partially filled with the solid heating medium and thereby at least one heatable by electromagnetic induction heating zone, wherein the reaction medium the Passage through the flow reactor and wherein the inductor is outside the reactor.

9. The method according to claim 8, characterized in that the reaction medium flows through each flow reactor at such a rate that the contact time of the reaction medium with the heating medium in each reactor in the range of one Second to 2 hours.

10. The method according to one or more of claims 1 to 9, characterized in that the reaction medium is present in each reactor as a liquid.

1 1. The method according to one or more of claims 1 to 10, characterized in that each inductor generates an alternating field having a frequency in the range of 1 to 100 kHz, preferably in the range of 10 to 80 kHz and in particular to 50 kHz.