WO2022152768A1 - Procédé et système à flux continu pour la préparation de complexes métal-carbène - Google Patents

Procédé et système à flux continu pour la préparation de complexes métal-carbène Download PDF

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Publication number
WO2022152768A1
WO2022152768A1 PCT/EP2022/050574 EP2022050574W WO2022152768A1 WO 2022152768 A1 WO2022152768 A1 WO 2022152768A1 EP 2022050574 W EP2022050574 W EP 2022050574W WO 2022152768 A1 WO2022152768 A1 WO 2022152768A1
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metal
carbene
reaction
reaction zone
continuous flow
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PCT/EP2022/050574
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English (en)
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Steven Nolan
Christian Stevens
Catherine Cazin
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Universiteit Gent
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic System
    • C07F1/005—Compounds containing elements of Groups 1 or 11 of the Periodic System without C-Metal linkages
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J8/00—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes
    • B01J8/02—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with stationary particles, e.g. in fixed beds
    • B01J8/04—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with stationary particles, e.g. in fixed beds the fluid passing successively through two or more beds
    • B01J8/0403—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with stationary particles, e.g. in fixed beds the fluid passing successively through two or more beds the fluid flow within the beds being predominantly horizontal
    • B01J8/0423—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with stationary particles, e.g. in fixed beds the fluid passing successively through two or more beds the fluid flow within the beds being predominantly horizontal through two or more otherwise shaped beds
    • B01J8/0438—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with stationary particles, e.g. in fixed beds the fluid passing successively through two or more beds the fluid flow within the beds being predominantly horizontal through two or more otherwise shaped beds the beds being placed next to each other
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System
    • C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System compounds of the platinum group
    • C07F15/006—Palladium compounds
    • C07F15/0066—Palladium compounds without a metal-carbon linkage
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2208/00—Processes carried out in the presence of solid particles; Reactors therefor
    • B01J2208/02—Processes carried out in the presence of solid particles; Reactors therefor with stationary particles
    • B01J2208/023—Details
    • B01J2208/024—Particulate material
    • B01J2208/025—Two or more types of catalyst

Definitions

  • the most common synthetic one-pot strategy to prepare heterocyclic carbene-metal complexes and in particular nitrogen-containing heterocyclic carbene (NHC)-metal complexes is based on the reaction of a free carbene with a metal source, wherein the free carbene is particularly obtained by deprotonation of the corresponding azolium salt with a strong base.
  • the most important drawbacks of this so-called “free carbene” synthesis method lies in the need for strictly anhydrous conditions. The method is also highly sensitive to oxygen and thus requires working in an inert atmosphere. Furthermore, this method is not suitable for complexes requiring the use of metal precursors sensitive to strong bases. The method is expensive and has a high negative impact on the environment.
  • This synthesis protocol is a one-pot, batch type method for the preparation of NHC-metal complexes, wherein a weak base is mixed with an azolium salt and a metal precursor of interest in a suitable solvent.
  • the “weak- base” preparation protocol allows to obtain NHC-metal complexes in a single step, with high atom efficiency at mild conditions.
  • this process requires separation of the NHC-metal complex from the reaction mixture. This process further makes use of large solvent volumes and requires long reaction times of on average 6h or more. Also, the yield of the NHC-metal complex is limited by the reduced stability of the NHC- metal complex in the reaction mixture.
  • the present inventors have developed improved methods and systems that address one or more of the above-mentioned problems in the art.
  • the present invention envisages a continuous flow process for the preparation of metal-carbene complexes comprising the use of a continuous flow reactor containing a solid weak base, such as K2CO3, allowing to obtain highly pure metal carbene complexes in high yield and at mild reaction conditions.
  • the inventors have surprisingly found that by passing a solution comprising an azolium salt, such as an imidazolium salt, and a metal precursor ML n over a bed of a weak base, such as K2CO3, in a continuous flow reactor, NHC-metal complexes can be obtained in high yield, at short reaction times and with a high conversion ratio.
  • a first aspect of the present invention relates to a continuous flow process for the preparation of a carbene-metal complex, said process comprising the steps of
  • step (i) comprises continuously mixing a solution comprising a salt of formula Z + -X' with a solution comprising a metal salt of formula ML n , preferably a nonionic metal salt of formula ML n , thereby obtaining said reaction medium, particularly thereby obtaining a reaction medium comprising a metallate of formula Z + -ML n X’ and the organic solvent.
  • step (i) comprises the steps of
  • step (ib) prior to step (ii), continuously passing said solution comprising said salt through a second reaction zone comprising a metal salt of formula ML n , preferably a non-ionic metal salt of formula ML n in solid form, thereby obtaining said reaction medium.
  • the continuous flow process according to the present invention further comprises the step of
  • the weak base is selected from the group consisting of carbonates, hydrogen carbonates, phosphates and amines, preferably is an alkali metal carbonate, alkali metal hydrogen carbonate, alkali metal phosphate, more preferably is K2CO3 or Na 2 CC>3.
  • the organic solvent is acetone, isopropyl acetate, ethyl acetate or ethanol.
  • Z is a nitrogen-containing heterocyclic carbene (NHC), preferably a substituted imidazoline-2-ylidene, a substituted 4,5-dihydroimidazol-2-ylidene, a substituted imidazoline-4-ylidene, a substituted 4,5-dihydroimidazol-4-ylidene, a substituted mesoionic carbene (MIC) or a cyclic(alkyl)(amino)carbene (CAAC), more preferably selected from the group consisting of IMes, SIMes, IPr, SIPr and ItBu, as specified elsewhere herein, and/or
  • X is selected from the group consisting of halides, carboxylates, alkoxy groups, aryloxy groups, alkylsulfonates, acetates, trifluoroacetates, tetrafluoroborates, hexafluorophosphates, hexafluoroantimonates, cyanides, thiocyanates, isothiocyanates, cyanates, isocyanates, azides and selenocyanates.
  • M is a transition metal, preferably M is copper, iron, nickel, manganese, ruthenium, osmium, chromium, cobalt, silver, gold, palladium, platinum, iridium or rhodium; and/or L is selected from the group consisting of fluoride (F-), chloride (Cl"), bromide (Br), iodide (I-), triflate (trifluoromethane sulfonate) (OTf), acetate (OAc), trifluoroacetate (TFA-), tetrafluoroborate (BF4'), hexafluorophosphate (PFe’), hexafluoroantimonate (SbFe'), sulfate (SC>4 2 ') and phosphate (PCs 2- ).
  • step (ii) of the continuous flow process according to the present invention is conducted at a temperature between 20°C and 60°C, preferably between 30°C and 50°C, and with a contact time between reaction medium and the solid weak base of between 1 min and 10 min, preferably between 2 min and 5 min.
  • the continuous flow process as envisaged herein further comprises the step (iii) of continuously adding a further reactant to the product flow comprising a carbene-metal complex in an organic solvent obtained in step (ii), thereby obtaining a combined product flow, and continuously subjecting the combined product flow to conditions suitable for the reaction between the further reactant and the carbene-metal complex in the product flow.
  • the continuous flow process as envisaged herein further comprises the step (iiia) of continuously adding a carbazole, a p-carboline, an alkyne, a heteroaromatic compound, a heterocycle or a thiol compound in an organic solvent to the product flow comprising a carbene-metal complex in an organic solvent obtained in step (ii), thereby obtained a combined product flow, and (iiib) continuously passing said combined product flow through a third reaction zone comprising a packed bed of a weak base as specified herein, thereby continuously obtaining a further product flow comprising a further metal- carbene complex in the organic solvent, said further metal-carbene complex comprising a ligand Y derived from a carbazole, a p-carboline, an alkyne, a heteroaromatic compound, a heterocycle or a thiol.
  • step (iiib) is conducted at a temperature between 20°C and 70°C, preferably between 30°C and 60°C, and with a contact time between the combined product flow and the solid weak base of between 1 min and 10 min, preferably between 2 min and 5 min.
  • the weak base of the third reaction zone is selected from the group consisting of carbonates, hydrogen carbonates, phosphates and amines, preferably is an alkali metal carbonate, alkali metal hydrogen carbonate or an alkali metal phosphate, more preferably is K2CO3 or Na2COs.
  • Another and related aspect of the present invention provides a system for the continuous preparation of a carbene-metal complex, comprising a reaction vessel, said reaction vessel comprising:
  • At least one first reaction zone comprising a packed bed of a solid weak base, wherein the weak base is not capable of deprotonating a protonated carbene ligand, such as an azolium salt;
  • at least one inlet in fluid communication with a first end of the at least one first reaction zone, for introducing a reaction medium in the reaction vessel;
  • the system according to the present invention further comprises a mixing means for the preparation of a reaction medium, said mixing means comprising at least an inlet for a solution of a salt of formula Z + -X' in an organic solvent, an inlet for a solution of a metal salt of formula ML n , particularly a non-ionic metal salt of formula ML n , in the organic solvent, and an outlet for the reaction medium, wherein the outlet of the mixing means is connected to the inlet of said reaction vessel.
  • the system according to the present invention further comprises at least a second reaction zone, comprising a metal salt of formula ML n in solid form, particularly a non-ionic metal salt of formula ML n in solid form, in fluid communication to and upstream of at least one first reaction zone, such as wherein the reaction vessel comprises multiple, alternating first and second reaction zones.
  • at least one first reaction zone is separated from said at least one second reaction zone by an inert filler material, such as sand or SiC>2.
  • the third reaction zone comprises a packed bed of a solid weak base.
  • Figure 1 represents a system according to an embodiment of the present invention.
  • Figure 2 represents a system according to an embodiment of the present invention.
  • Figure 3 represents a system according to an embodiment of the present invention.
  • Z is an NHC ligand according to formula (I)
  • R, R1 , R2, R3 and R4 of structures of formula (II) may include alkyl and unsaturated alkyl groups, aryl or heteroaryl groups that may be substituted.
  • Z is a substituted imidazoline-2-ylidene, a substituted 4,5-dihydroimidazol-2-ylidene, a substituted imidazoline-4-ylidene, or a substituted 4,5- dihydroimidazol-4-ylidene.
  • Z is a substituted mesoionic carbene (MIC) or a cyclic(alkyl)(amino)carbene (CAAC).
  • Particularly preferred examples of an NHC ligand include any one of the carbenes listed in Table A.
  • a salt of formula Z + -X' and a metal salt of formula ML n is contacted or provided in an organic solvent, thereby forming a reaction medium, and continuously passing this reaction medium over a fixed bed comprising a solid weak base, as further specified below.
  • the reaction medium comprises a metallate of formula Z + -ML n X’.
  • a salt of formula Z + -X' is a salt of a substituted mesoionic carbene (MIC) or a cyclic(alkyl)(amino)carbene (CAAC), such as the hydrogen halide or acetic acid salt thereof.
  • MIC substituted mesoionic carbene
  • CAAC cyclic(alkyl)(amino)carbene
  • Particular preferred examples are a salt of the NHC ligands listed in table A, more in particular a hydrogen halide salt, such as a HCI salt of the NHC ligands listed in table A.
  • a metal salt of formula ML n includes all salts comprising metal M and anion or electron donor ligand L.
  • the metal salt is a nonionic metal salt of formula ML n , which includes all salts comprising metal M and electron donor ligand L, that are not ionic salts.
  • Ionic salts refer to salts of formula M x+ L n y ' whereby the metal and the anion are bonded by an ionic bond.
  • Preferred non-ionic metal salts used in the method according to the present invention comprise compounds whereby the metal M and the anion L are bonded by a covalent or dative bond.
  • M is a metal as envisaged herein.
  • the weak base is not soluble in the organic solvent.
  • the weak base is selected from the group consisting of carbonates, hydrogen carbonates, phosphates and amines, preferably is an alkali metal carbonate, alkali metal hydrogen carbonate or an alkali metal phosphate, more preferably is K2CO3 or Na2COs.
  • the reaction zone comprising the weak base is contained in a suitable reaction vessel.
  • the continuous flow process as envisaged herein further comprises the step (iii) of continuously adding a further reactant to the first product flow comprising a carbene-metal complex in an organic solvent, obtained in step (ii), thereby obtaining a combined product flow, and continuously subjecting the combined product flow to conditions suitable for the reaction between the further reactant and the carbene-metal complex in the product flow.
  • said step (iii) comprises the step (iiia) of continuously adding a further reactant selected from the group consisting of a carbazole, a p-carboline, an alkyne, a heteroaromatic compound, a heterocycle and a thiol compound, in an organic solvent to the product flow comprising a carbene-metal complex, particularly an NHC-metal complex, in an organic solvent, obtained in step (ii), thereby obtained a combined product flow, and (iiib) continuously passing said combined product flow through a third reaction zone comprising a packed bed of a weak base, thereby continuously obtaining a further product flow comprising a further metal-carbene complex in an organic solvent, wherein the further metal-carbene complex further comprises a ligand Y derived from said carbazole, a p-carboline, an alkyne, a heteroaromatic compound, a heterocycle or a thiol.
  • a further reactant selected from the group consisting of
  • heteroaromatic compound generally refers to but is not limited to a compound comprising 5 to 20 carbon-atom aromatic rings or ring systems, wherein each ring typically contains 5 to 6 atoms; at least one of which is aromatic in which one or more carbon atoms in one or more of these rings can be replaced by oxygen, nitrogen or sulfur atoms, preferably by nitrogen atoms.
  • Preferred heteroaromatic compounds include carbazole or p-carboline.
  • p-carboline represents a family of alkaloid compounds, particularly indole alkaloids sharing the basic chemical structure of Formula III.
  • the present invention relates to a continuous flow process for the preparation of a metal-NHC amido or metal-NHC thiolato complex, said process comprising the steps of
  • step (iiib) is conducted at a temperature between 20°C and 70°C, preferably between 30°C and 60°C, and with a contact time between the combined product flow and the solid weak base of between 1 min and 10 min, preferably between 2 min and 5 min.
  • step (iiia) at least 1.1 equivalents, such as between 1.1 or 1.2 and 1.5 equivalents of carbazole or p-carboline, based on the amount of a carbene-metal complex, particularly an NHC-metal complex, in the first product flow, are introduced in the first product flow.
  • a system for the continuous preparation of a metal-carbene complex comprises a reaction vessel, wherein the reaction vessel comprises: (a) at least one first reaction zone, said first reaction zone comprising or consisting of a packed bed of a solid weak base as specified elsewhere herein; (b) at least one inlet, in fluid communication with a first end of the at least one first reaction zone, for introducing an inlet flow, particularly for introducing a reaction medium as envisaged herein, in the reaction vessel; and
  • the inlet flow is typically introduced to the reaction zone by continuously pumping the inlet flow, via a pumping means, particularly the reaction medium to the reaction vessel and through a reaction zone of the reaction vessel.
  • the system or reaction vessel further comprises at least a second reaction zone, different from the first reaction zone.
  • said second reaction zone comprises or consists of a metal salt of formula ML n in solid form as envisaged herein, particularly a non-ionic metal salt of formula ML n in solid form, in fluid communication to an end of the at least one reaction zone.
  • the reaction vessel comprises multiple, alternating first and second reaction zones.
  • the system according to the present invention may comprise a plurality of reaction vessels, wherein each reaction chamber comprises one or more first and, optionally, second reaction zones. More in particular, each of said first reaction zones is separated from each of said second reaction zones by an inert filler material, such as sand or SiC>2.
  • the inlet flow comprising the reaction medium as envisaged herein may be obtained by mixing a first flow of a salt of formula Z + -X' as envisaged herein in an organic solvent and a second flow of a metal salt of formula ML n as envisaged, particularly a non-ionic metal salt of formula ML n .
  • the system further comprises a mixing means upstream of the reaction vessel, and in fluid communication with the at least one inlet, for mixing a first flow of a salt of formula Z + -X' as envisaged herein in an organic solvent as envisaged herein and a second flow of a non-ionic metal salt of formula ML n as envisaged herein in the solvent, thereby obtaining a flow of the reaction medium.
  • Suitable mixing means are known in the art and include, but are not limited to, a static mixer.
  • the system further comprises (d) a third reaction zone, preferably located in a separate reaction vessel, wherein the inlet of the third reaction zone is in fluid connection with the outlet of the first reaction zone, and (e) a means for introducing a reactant in the product flow between the outlet of the first reaction zone and the inlet of the third reaction zone.
  • the third reaction zone comprises a packed bed of a solid weak base, as specified elsewhere herein.
  • FIG 1 is an exemplary illustration of a system (100) for the continuous preparation of a metal-carbene complex according to an embodiment of the present invention.
  • a flow of reactant A and a flow 102 of reactant B is provided via the respective conduits (101 , 102) to a mixer (103), for example a static mixer or any other mixing system, resulting in a combined flow comprising the reaction medium.
  • Reactant A comprises a salt of formula Z + - X' as envisaged herein in an organic solvent as envisaged herein.
  • Reactant B comprises for example a non-ionic metal salt of formula ML n as envisaged herein in the solvent.
  • the reaction medium flow is introduced by a conduit (104) to a reaction vessel (105) to flow through reaction zone (106).
  • the reaction medium flow is introduced by a conduit (304) to a reaction vessel (305) to flow through a first reaction zone (306).
  • the reaction zone (306) comprises a packed bed of a solid weak base as envisaged herein, such as e.g. K2CO3.
  • the temperature of the reaction chamber is thermostatically controlled (not shown).
  • the product flow comprising the metal-carbene complex is removed from the first reaction zone (306) and reaction vessel (305) via conduit (307) and introduced into another reaction vessel (308) comprising a third reaction zone (309), which comprises a packed bed of a solid weak base as envisaged herein, such as e.g. K2CO3.
  • the 1 H NMR spectra were recorded at 400 MHz, on a Bruker AVANCE III spectrometer, equipped with 1 H/BB z-gradient probe (BBO, 5 mm). CDC was added as solvent for all analysis, and TMS was used as an internal chemical shift standard. All spectra were processed using TOPSPIN 3.6.2. In all cases, the measured spectral data were in accordance with literature.
  • the reactor was filled with different plugs (or reactor beds) of solid material.
  • the reactor comprised a plug made up of a mixture of base (K2CO3) and metal source (CuCI).
  • the reactor contained either a (single) K2CO3 plug or a plug alternating between base (K2CO3) and metal source (CuCI), separated by a filler, SiO2 or sand.
  • Example 1 reactor comprising at least two reaction zones for preparing Cu-NHC complex
  • Example 2 reactor comprising one reaction zone (base) for the preparation of Cu- NHC complex
  • a cuprate solution (0.03 M solution of [IPrH CuCh] in acetone) was prepared by mixing, such as by sonification, the corresponding imidazolium salt (IPr-HCI) and CuCI for 5 min at RT in green acetone (255 mg of IPr.HCI in 20 mL acetone + 59 mg CuCI (1.0 equiv)).
  • the cuprate may be obtained by a dry milling process according to WQ2020/048925, and can be dissolved directly in acetone (e.g. 3.14 mg in 20 mL acetone).
  • the cuprate solution was then continuously injected into a reactor comprising a solid base plug (1.5 g K2CO3 in a 55 cm long tubing), at a temperature of 50°C and with a residence time of 5 min. A clear product solution was recovered after the column, and upon evaporation of the solvent under vacuum, a final product powder was obtained.
  • a solid base plug 1.5 g K2CO3 in a 55 cm long tubing
  • a reagent is provided to the reactor which already contains the metal and azolium components in the correct ratio. It also allows to use a simple reactor design, only containing a reactor bed filled with the solid base.
  • Example 3 reactor comprising one reaction zone (base) for the preparation of Au- NHC complex
  • the decomposition processes inside the reactor were reduced while maintaining high substrate conversion by using a lower operating temperature and residence time for the process.
  • Example 4 reactor comprising one reaction zone (base) for the preparation of a Pd- NHC complex
  • 3-cinnamyl)] was prepared by passing a 0.03 M solution of [Pd(CI)(r
  • a particularly advantageous setup consists of a microreactor filled with potassium carbonate, which is a weak and inexpensive base, into which is injected a technical grade acetone solution of an imidazolium salt (e.g. IPr HCI) and a metal precursor (e.g. CuCI, Au(DMS)CI or [Pd(CI)(r
  • IPr HCI an imidazolium salt
  • a metal precursor e.g. CuCI, Au(DMS)CI or [Pd(CI)(r
  • a major advantage to the use of continuous flow synthesis is the potential to access desired compounds at significantly higher reaction rates compared to batch synthesis.
  • Another important advantage, mainly in terms of time management, is provided by performing one-pot or telescoping reactions.
  • multiple reagent streams can be coupled in series. Therefore, multi-step procedures can be established by sequentially interconnecting reactor columns and by introducing new reagents at set intervals in the continuous flow sequence.
  • a first reactor comprising a packed bed of K2CO3 was used for the synthesis of [Cu(l Pr)CI] (2), essentially as in example 2 above, using acetone as solvent, with a reaction temperature of 50°C or 60°C and a residence time of 2 min.
  • the product flow of the first reactor, comprising [Cu(IPr)CI] dissolved in acetone was in turn immediately fed into a second reactor comprising a packed bed of K2CO3 with concomitant introduction of a carbazole solution (with acetone or ethanol as solvent).
  • reaction temperature of 50 °C and a residence time of 2 minutes allowed to obtain [Cu(IPr)(Cbz)] in high yield and in unprecedentedly short reaction times, without the need for wasteful intermediate purification steps.
  • a first reactor comprising a packed bed of K2CO3 was used for the synthesis of [Cu(l Pr)CI], essentially as in example 2 above, using acetone as solvent, with a reaction temperature of 50°C or60°C and a residence time of 2 min.
  • the product flow of the first reactor, comprising [Cu(IPr)CI] dissolved in acetone was in turn immediately fed into a second reactor comprising a packed bed of K2CO3 with concomitant introduction of a thiophenol solution (with acetone as solvent). Applying similar reaction conditions as in the first reactor, i.e.
  • reaction temperature ranging between 30°C to 60°C and a residence time of 1 to 2 minutes, allowed to obtain [Cu(IPr)(SPh)] in high yield and in unprecedentedly short reaction times, without the need for wasteful intermediate purification steps.
  • adding stoichiometric amounts of thiophenol to the product flow of the first reactor results in full conversion thus eliminating the need for additional workup to remove any additional/unreacted thiophenol.

Abstract

La présente invention concerne un procédé et un système à flux continu pour la préparation de complexes métal-carbène, comprenant l'utilisation d'un réacteur à flux continu contenant une base faible solide, tel que le K2CO3, ce qui permet d'obtenir des complexes de métal-carbène très purs avec un rendement élevé, des temps de réaction courts et des conditions de réaction modérées. En particulier, le procédé à flux continu de la présente invention comprend le passage continu d'un milieu réactionnel comprenant un sel de formule Z+-X-, tel qu'un sel d'azolium, et un sel métallique de formule MLn sur un lit de type base faible , tel que le K2CO3 dans un réacteur à flux continu, ce qui permet d'obtenir un complexe carbène-métal.
PCT/EP2022/050574 2021-01-13 2022-01-13 Procédé et système à flux continu pour la préparation de complexes métal-carbène WO2022152768A1 (fr)

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WO2020048925A1 (fr) 2018-09-03 2020-03-12 Universiteit Gent Procédé de préparation de complexes métalliques de formule z-m, en particulier de complexes carbène-métal

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Publication number Priority date Publication date Assignee Title
WO2020048925A1 (fr) 2018-09-03 2020-03-12 Universiteit Gent Procédé de préparation de complexes métalliques de formule z-m, en particulier de complexes carbène-métal

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