Method for producing organometallic compounds

Abstract

The invention relates to a method for producing a compound of the general formula 1 by reacting a compound of the formula 2 with an NHC ligand precursor compound of the formula, said NHC ligand precursor compound being reacted with a base in situ in order to form the free NHC ligand which reacts with the compound of the formula 2 in a one-pot reaction without an intermediate isolation in order to produce the compound of the formula 1.

Description

Procedure for K. Kuhn and RH Grubbs described a one-step method for the preparation of symmetrical 1,3-diarylimidazolinium salts and two two-step methods for the preparation of unsymmetrical 1,3-diarylimidazolinium salts, where aryl = phenyl, naphthyl, or anthracenyl. (WO 2009 / 062171 A1: unsubstituted or substituted aryl residues; Organometallics 2008, 10 (10), 2075-2077: substituted aryl residues) All three methods use formamidines as starting materials and are carried out solvent-free. They work well with electron-rich anilines as starting materials, but not with anilines bearing very bulky or electron-withdrawing substituents. Starting from anilines with less bulky substituents, symmetrical imidazolinium salts could be prepared in a one-pot synthesis. The in situ formed formamidine also acted as a base (cf. WO 2009 / 062171 A1 :

[0010] ,

[0032] ,

[0036] ,

[0052] , Examples 13 - 18; Organometallics 2008, 10 (10), 2075 - 2077, Table 2 and Supporting Information, pages 2 - 4). WO 2009 / 062171 A1 discloses that imidazolinium salts containing, for example, a tosylate or triflate anion are also obtainable by means of the presented processes. However, all synthesized compounds are 1,3-diphenyl-substituted imidazolinium halides, namely chlorides and bromides. Furthermore, it is disadvantageous that the preparation of unsymmetrical 1,3-diarylimidazolinium salts requires the use of a previously purified and isolated formamidine. (cf. WO 2009 / 062171 A1:

[0064] , Example 20 and

[0065] , Example 21 ; Organometallics 2008, 10 (10), 2075 - 2077, Table 1 and Supporting Information, pages 6 and 7) Further methods for the preparation of Grubbs catalysts are shown in “Simple synthetic routes to ruthenium-indenylidene olefin metathesis catalysts” Doppiu, A., Nolan S. et al., Chem. Commun., 2011 ,47, 5022-5024 and “Comparative Investigation of Ruthenium-Based Metathesis Catalysts Bearing N-Heterocyclic Carbene (NHC) Ligands” Fürstner, A. et al., “Chemistry - A European Journal”, 2001 , Vol 7, Issue 15, pages 3236-3253. Further methods for the preparation of Hoveyda catalysts are shown in "Chelated Ruthenium Catalysts for Z-Selective Olefin Metathesis" Grubbs, RH et al., J. Am. Chem. Soc. 2011 , 133, 22, 8525-8527. In 2011, a method for the preparation of symmetric and asymmetric imidazolinium triflates was published. It involves the reaction of a formamidine with (2-bromoethyl)diphenylsulfonium triflate (1.25 molar equivalents) in the presence of diisopropylethylamine (DIPEA, Hünig's base, 2.5 molar equivalents) in a polar solvent. (EM McGamgle, SP Fritz, L. Favereau, M. Yar, VK Aggarwal, Org. Lett. 2011, 13 (12), 3060-3063) Using ethyl acetate or acetonitrile, very good yields of 90% and 91%, respectively, were achieved within relatively short reaction times of 3 and 2.5 hours, respectively.Both symmetrical 1,3-disubstituted imidazolinium triflates could be prepared, where the imidazolinium cations have two identical aromatic or aliphatic groups, and unsymmetrical imidazolinium triflates, whose cations either carry two different aromatic substituents or one aromatic and one aliphatic, namely an unsubstituted phenyl radical and a 1-adamantyl or cyclohexyl radical. Many processes for producing metathesis catalysts are unstable, yield products of insufficient quality, or are operationally difficult to implement. The aim is to produce the products cleanly, in very good yield and quality, and using simple, scalable processes. The invention is therefore based on the object of overcoming these and other disadvantages of the prior art and of providing a process by which ruthenium complexes suitable as metathesis catalysts can be prepared in high purity and good yield in a simple, reproducible, and comparatively cost-effective manner. The process should also be distinguished by the fact that it can also be carried out on an industrial scale - with comparable yield and purity of the target compounds. By means of this process, ruthenium(II) complexes which have an NHC ligand (N-heterocyclic carbene ligand) can be prepared in high purity and good yield in a simple, reproducible, and comparatively cost-effective manner. Furthermore, ruthenium(II) complexes and preparations thereof are the subject of the present invention. The main features of the invention are set out in the patent claims. The problem is solved by a process for preparing a compound according to the general formula 1 NHC CI Rü=\ CI Z Ar I- Formula 1 at the NHC an NHC ligand, L is a phosphine or an alkoxy group, Ar is an aromatic group bridged to L when L is an alkoxy group, by reacting a compound of formula 2 Formula 2 where L2 is a phosphine and the other definitions correspond to those of formula 1, with an NHC ligand precursor compound of the formula in which Ad is adamantyl, or an aromatic group, Ar is an aromatic group and the NHC ligand precursor compound is reacted with a base in situ to form the free NHC ligand, which reacts with the compound of formula 2 without intermediate isolation in a one-pot reaction to form the compound of formula 1, characterized in that the process is carried out in an alkane or cycloalkane having 5 to 15 carbon atoms as solvent; lithium hexamethyldisilazide (LiHMDS) is used as base; the compound of formula 2 is selected from the group consisting of the compounds of formulas M100, M102 and M700; M100 M102 M700 and the NHC ligand precursor compound is selected from the group consisting of the compounds of the formulas where the abbreviations of the substituents iPr for isopropyl, Ph for phenyl, Cy for Cyclohexyl and X stands for CI, tosylate and tetrafluoroborate. Advantageously, this process is used to prepare compounds of formula 1 which are selected from the group consisting of the compounds of formulas M201, M206, M725 and M726 M201 M206 The invention also relates to compounds of the formulas M201, M206, M725, and M726, as well as preparations thereof, whose lithium content is > 10 ppm and < 100 ppm. By using lithium bis(trimethylsilyl)amide LiHMDS, a carbene is prepared in situ from the NHC ligand precursor compound (NHC salt such as chloride, BF4, or tosylate) and reacted directly with the Ru reactant of formula 2 in a hydrocarbon solvent. The product can be isolated, for example, by filtration and washing. Yields are generally above 85%. The solvent for the reaction is an alkane or cycloalkane having 5 to 15 carbon atoms, in particular 5 to 12 or 5 to 9 or 5 to 8 carbon atoms, or mixtures thereof, or a combination of alkanes or cycloalkanes having 5 to 15 carbon atoms, in particular selected from the group consisting of cyclohexane, cyclopentane, cyclooctane, pentane, hexane, heptane, decane, dodecane and their isomers, petroleum ether and combinations thereof, but in particular heptane, petroleum ether and combinations thereof. "Petroleum ether" as used herein refers to a colorless mixture of various saturated hydrocarbons, for example, pentane and hexane.These solvents have the technical effect that the reaction product, the compound of formula 1, precipitates from the solvent and in this way a higher purity can be achieved, since the reaction product, the compound of formula 1, precipitates from the solvent and has a purity of at least 95%, in particular at least 97% or at least 98%. Advantages of the process according to the compound are in particular high space / time yield, since one-pot process high purity simple implementation of the procedure and its scalability “Space-time yield” is understood here as the amount of product formed per space and time within a reaction vessel. It is particularly advantageous that the process described here is a multi-stage one-pot synthesis or one-pot reaction. The term "multi-stage one-pot synthesis" here means that the process for preparing the compound of formula 1 proceeds in several steps, in particular two steps. However, the intermediates obtained from the reaction of the NHC ligand precursor compound with lithium bis(trimethylsilyl)amide LiHMDS are generated in situ. The process presented here, in particular a two-stage process, can therefore advantageously be carried out in one and the same reaction vessel. Isolation, e.g., by filtration, and / or purification, e.g., by washing, of the intermediate can be dispensed with. This is particularly advantageous from an (atom-)economic and ecological perspective. The term "in situ production" or "in situ production" means that the reactants required for the synthesis of a compound or intermediate to be prepared in this way are reacted in a suitable stoichiometry in a solvent or solvent mixture, and the resulting intermediate is not isolated. Rather, the solution or suspension containing the intermediate generated in situ is used directly, i.e., without isolation and / or further purification. The term "preparation" here and below refers to a solution, a suspension, a dispersion or a gel. The preparation can therefore be in the form of a solution, suspension, dispersion or gel, particularly depending on the solvent and / or the compound according to formula I contained. The solvent can also be a solvent mixture. The solvent can also be a solvent mixture comprising two or more solvents. The solvent in the preparation is compatible with the reaction medium used. Solvent identical and thus a hydrocarbon, in particular selected from the group consisting of pentane, hexane, heptane, decane, dodecane and their isomers, petroleum ether and combinations thereof, but in particular heptane, petroleum ether and combinations thereof. Advantageously, after completion of the reaction, the reaction mixture generally contains only the desired target compound, the solvent SR, the compound Base-HX formed as a by-product, and the unreacted base Li-HMDS. The solvent, the by-product Base-HX, and the unreacted base can be removed quantitatively or almost quantitatively using simple and few steps. A variant of the process includes isolation as a further process step. The prepared compounds according to general formula I can be subjected to filtration and / or centrifugation and / or decantation, but filtration is sufficient. Overall, the purification and / or isolation of the target compound according to formula I, if required, is particularly simple and cost-effective. The high purity, particularly the absence of halide anions, of the imidazolinium salts obtainable by the process described above is particularly advantageous with regard to their applications, for example, as organocatalysts or as NHC precursors. When the imidazolinium salts obtained in this way are used as NHC precursors for the synthesis of second-generation Grubbs or Hoveyc / a catalysts, unwanted anion exchange reactions at the ruthenium are prevented. This is particularly advantageous because the aforementioned exchange reactions result in product mixtures that are either impossible or very difficult to separate, as explained above. The isolation of the compound of formula 1 , for example a second generation Grubbs catalyst or a second generation Hoveyc / a catalyst, as a preparation or as a substance may comprise further process steps such as reducing the volume of the mother liquor, ie concentration, adding a Solvent and / or solvent exchange to achieve precipitation of the product from the mother liquor and / or to remove impurities and / or reactants, washing. The aforementioned steps can each be performed in different sequences and frequencies. Overall, the purification and / or isolation of the organometallic compound containing a / V-heterocyclic carbene ligand, if required, is relatively simple and cost-effective. In general, the final product isolated as a substance may still contain residues of solvents and / or a salt obtained as a by-product, for example LiCI, LiBF4 or LiOTs. A compound of formula 1 isolated as a substance, advantageously as a solid, has a purity of at least 97%, advantageously more than 97%, in particular more than 98% or 99%. The reproducible yield is typically > 85% or > 95%, particularly depending on the choice of the imidazolinium salt according to formula I, the metal precursor, and the solvent—even in the case of upscaling toward an industrial scale. The object is further achieved by a preparation, in particular obtained or obtainable by a process according to one or more of the embodiments described above, in particular comprising one or more compounds of the formulas M201, M206, M725 and M726. In one embodiment of the preparation, the solvent is selected from the group consisting of aliphatic hydrocarbons, advantageously having 5 to 12 carbon atoms; further details on the solvent are given above in connection with the process for preparing the compounds. For example, the solvent can be selected from the group consisting of pentane, hexane, heptane, decane, dodecane, and their isomers. Petroleum ether refers to In this case, a colourless mixture of various saturated hydrocarbons is meant, for example pentane and hexane. The fact that the compounds of formula 1 obtainable by the process described above, for example compounds of formulas M201, M206, M725 and M726 and the preparations comprising such a compound, have only low levels of impurities by lithium ions, is particularly advantageous with regard to their use as precatalysts or catalysts. With regard to further advantages of the organometallic compounds and preparations described here, comprising such an organometallic compound, each obtained or obtainable by a process for preparing such compounds and preparations according to one or more of the embodiments described above, reference is made to the advantages mentioned for the process described above for preparing such an organometallic compound or preparation. Further features, details, and advantages of the invention will become apparent from the wording of the claims, from the examples and working instructions, and from the following description of exemplary embodiments with reference to the figures. They show: Materials and methods All reactions were carried out under standard inert gas conditions. The solvents and reagents used were purified and dried according to standard procedures. All nuclear magnetic resonance measurements were performed on a Bruker FT-NMR spectrometer. 13 C-NMR spectra were standardly 1 H-broadband decoupled measured at 300 K. 1 Dog 13 C-NMR spectra were calibrated to the corresponding residual proton signal of the solvent as an internal standard: 1 H: CD2CI2: 5.32 ppm (singlet); 13C: CD2Cl2: 53.8 ppm (singlet). Chemical shifts are given in ppm and refer to the α-scale. All controls by gas chromatographic analysis were carried out under the conditions The following conditions apply: ■ GC column: HP-5 (Agilent Technologies), 30 m x 0.25 mm (ID) x 0.25 pm film thickness ■ Injector temperature: 250 °C ■ Detector temperature: 280 °C ■ Oven temperature: ■ Starting temperature: 100 °C, holding time: 1 min ■ Heating rate 10 °C / min to 270 °C, holding time: 12 min ■ Carrier gas: Helium ■ Average gas velocity: 30 cm / s ■ Split ratio: 40.8 : 1 M100 M201 1. Synthesis of Umicore Grubbs Catalyst M201 by the process according to the invention In a 10L reactor under an argon atmosphere, 3.5L of n-heptane were charged, and LiHMDS (168g, 0.97 mol, 1.40 eq.) was added portionwise with stirring. The reaction mixture was cooled to <10°C, and then SIPr*HCl (388g, 0.84 mol, 1.20 eq.) was added portionwise to the reaction mixture. The reaction was then stirred for 2h at 10°C and then for 1h at 25°C. Umicore Grubbs Catalyst M100 (725g, 0.69 mol, 1.00 eq.) and a further 500mL of n-heptane were added. The reaction mixture was warmed to 65°C and stirred for 20h. The reaction mixture was then cooled to 10°C and filtered. The remaining dark red solid was washed once with 250 mL of petroleum ether (50-70°C), then four times with 250 mL of methanol, and once again with 250 mL of petroleum ether (50-70°C). The resulting solid was dried under vacuum at 40°C for 16 h to obtain Umicore Grubbs Catalyst M201 (583 g, 0.56 mol, 81%) as a fine, dark red powder.Li content according to ICP-MS = 70 ppm. 31 P NMR purity >98%. 2. Synthesis of Umicore Grubbs Catalyst M201 according to the state of the art: “Simple synthetic routes to ruthenium-indenylidene olefin metathesis catalysts” Doppiu, A., Nolan S. et al., Chem. Commun., 2011, 47, 5022-5024. The compound was prepared as described using isolated free NHC-carbene ligands, working in a glove box without water and oxygen. The product was isolated by cooling at -40°C. Yield: 73%. Purity <98% based on 31 P NMR, product contains PPh3, OPPh3 and unknown impurities. 3. Synthesis of Umicore Grubbs Catalyst M206 according to the state of the art: "Comparative Investigation of Ruthenium-Based Metathesis Catalysts Bearing N- Heterocyclic Carbene (NHC) Ligands" Fürstner, A. et al., "Chemistry - A European Journal", 2001 , Vol. 7, Issue 15, pages 3236-3253 The compound was prepared as described; carbene formation occurred using KOtBu as the base in THF. Yield: 67%. Hydride-containing byproducts such as (PCy3)2Ru(H)2Cl2 were formed, which poisoned the metathesis catalyst. 4. Synthesis of Umicore Grubbs Catalyst M206 according to the procedure invention M102 SIPr*HCI M206 In a 1 L reactor, under an argon atmosphere, 600 mL of n-heptane were initially charged, and the reaction mixture was cooled to 5°C. LiHMDS (29.2 g, 169 mmol, 1.20 eq) was then added portionwise with stirring. SiPr*HCl (75.8 g, 176 mmol, 1.25 eq) was then added portionwise, followed by a further 150 mL of n-heptane. After the addition, the reaction mixture was stirred for 2 h at 10°C and then for 1 h at 25°C. Umicore Grubbs Catalyst M102 (120.0 g, 141 mmol, 1.00 eq) and a further 150 mL of n-heptane were then added to the reaction mixture, and the reaction mixture was stirred for 3 h at 65°C. The suspension was then cooled back to 20°C and filtered. The remaining filter cake was washed once with 100 mL of petroleum ether (50-70°C), then four times with 100 mL of methanol, and once again with 100 mL of petroleum ether (50-70°C).The resulting solid was dried under vacuum at 40°C for 16 h to obtain Umicore Grubbs Catalyst M206 (124 g, 132 mmol, 94%) as a dark yellow, crystalline solid. Li content according to ICP-MS = 80 ppm. 31 P NMR purity >98%. I. Preparation of imidazolinium tosylates Example 1.1 : (Ad-DIPP-NHC)OTs Step 1.A. 1 . PTSA (0.25 mol%) C 12 , 2.5 h, 90 °C 2,6-Diisopropylaniline (purity = 90%, 343 g, 1.93 mol), para-toluenesulfonic acid monohydrate (PTSA; 0.92 g, 4.84 mmol, 0.25 mol% relative to 2,6-Diisopropylaniline), triethyl orthoformate (TEOF; 321 g, 2.17 mol), and dodecane (330 g, 440 mL, 1.93 mol) were placed in a 3-L three-necked round-bottom flask equipped with an overhead stirrer and a short-path cooler. The reaction mixture was heated for 2.5 h under slow inert gas flow at an internal temperature of 90 °C. After 2.5 h, ethanol evolution had ceased, and quantitative gas chromatographic analysis of the reaction mixture revealed >95% conversion of 2,6-diisopropylaniline. Excess triethyl orthoformate was removed under vacuum (confirmed by quantitative GC analysis), and the crude product (ethyl- / V-(2,6-diisopropylphenyl)formimidate) was used without further purification to prepare formidine (see step 1.B.). Note: Instead of dodecane, for example, Isopar™ V (isoparaffin fluid from ExxonMobil Chemical) can also be used. Step 1.B. 1-Adamantylamine (322 g, 2.13 mol) was added to the reaction mixture from step 1.A. The reaction mixture was then heated for 24 hours under a slow stream of inert gas at an internal temperature of 180 °C. After 24 h, ethanol evolution had ceased, and quantitative gas chromatographic analysis of the reaction mixture revealed >95% conversion of ethyl- / V-(2,6-diisopropylphenyl)formimidate. After cooling the reaction mixture to room temperature, it was used without further purification to prepare (Ad-DIPP-NHC)OTs (see step 1.C.). Step 1.C. After replacing the short-path condenser with an efficient reflux condenser, 1,2-bis(tosyloxy)ethane (616 g, 1.66 mol) and / V, / V-diisopropylethylamine (650 g, 5.03 mol) were added to the reaction mixture from step 1.B. The reaction mixture was then heated for 18 h with a slow introduction of inert gas at an internal temperature of 120 °C. The reaction mixture was then allowed to cool to room temperature. The precipitated solid was collected by filtration and dissolved in dichloromethane (1.0 L). The solution was washed with water (3 x 1 L). The combined organic phases were dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was suspended in hexane (1.0 L). The precipitated solid was isolated by filtration, washed with hexane (2 x 300 mL) and dried in vacuo.600 g to 700 g of the target compound 1-(1-adamantyl)-3-(2,6-di / isopropylphenyl)imidazolinium tosylate were isolated (60% - 70% overall yield). Note: For example, instead of 1,2-bis(tosyloxy)ethane, 1,2-bis(trifluoromethanesulfonyl)ethane can also be used to produce 1-(1-adamantyl)-3-(2,6-di / isopropylphenyl)imidazolinium triflate Example I.2: (Ad-Mes-NHC)OTs Step 2.A. 1 . PTSA (0.9 mol%) C 12 , 2 hours, 85 °C -EtOH 2. Remove excess TEOF + 1.12 HC(OEt)3 2,4,6-Trimethylaniline (20 g, 0.148 mol), para-toluenesulfonic acid monohydrate (PTSA; 0.9 mol% based on 2,4,6-trimethylaniline), triethyl orthoformate (24.7 g, 1.67 mol), and dodecane (25.2 g, 33.6 mL, 0.148 mol) were added to a 3-L three-necked round-bottom flask equipped with an overhead stirrer and a short-path condenser. The reaction mixture was heated for 2 h with a slow flow of inert gas at an internal temperature of 85 °C. After 2 h, ethanol evolution had ceased, and quantitative gas chromatographic analysis of the reaction mixture revealed >95% conversion of 2,4,6-trimethylaniline. Excess triethyl orthoformate was removed in vacuo (confirmed by quantitative GC analysis) and the crude product (ethyl / V-(2,4,6-trimethylphenyl)formimidate) was used without further purification to prepare formidine (see step 1.B.). Note: Instead of dodecane, for example, Isopar™ V (isoparaffin fluid from ExxonMobil Chemical) can also be used. Step 2.B. 1-Adamantylamine (23.3 g, 0.154 mol) was added to the reaction mixture from step 2.A. The reaction mixture was then stirred for 12 h under a slow The reaction mixture was heated in an inert gas stream at an internal temperature of 150 °C. After 12 h, ethanol evolution had ceased, and quantitative gas chromatographic analysis of the reaction mixture revealed > 95% conversion of ethyl / V-(2,4,6-trimethylphenyl)formimidate. After cooling the reaction mixture to room temperature, it was used without further purification to prepare ((Ad-Mes-NHC)OTs (see step 2.C.). Step 2.C. C-|2 + 0.85 T or>^^ 0Ts + 2.8 EtN'Pr2 Mes I S(J 125 °C, 10 hours After replacing the short-path condenser with an efficient reflux condenser, 1,2-bis(tosyloxy)ethane (46.5 g, 0.126 mol) and A / ; / V-Diisopropylethylamine (52.6 g, 0.407 mol) was added to the reaction mixture from step 2.B. The reaction mixture was then heated for 10 h under slow introduction of inert gas at an internal temperature of 125 °C. The reaction mixture was then allowed to cool to room temperature. The precipitated solid was collected by filtration and dissolved in dichloromethane (150 mL). The solution was washed with water (3 x 250 mL). The combined organic phases were dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was triturated twice with acetone / hexane (20:80, 100 mL). The precipitated solid was isolated by filtration, washed with hexane (100 mL), and dried in vacuo. 37.5 g (60% overall yield) of the target compound 1-(1-adamantyl)-3-(2,4,6-trimethylphenyl)imidazolinium tosylate were isolated. Note: For example, instead of 1,2-bis(tosyloxy)ethane, 1,2-bis(trifluoromethanesulfonyl)ethane can also be used to produce 1-(1-adamantyl)-3-(2,4,6-trimethylphenyl)imidazolinium triflate. II. Description of the second generation Hoveyda-Gru bbs catalysts Example 11.1 : [1-(1-Adamantyl)-3-(2,6-diisopropylphenyl)-2-imidazolidinylidene]-dichloro(2-isopropoxybenzylidene)ruthenium(II) M726 1-(1-Adamantyl)-3-(2,6-diisopropylphenyl)imidazolinium tosylate (6.36 g, 12.0 mmol), hexane (60 mL), and a Teflon-coated magnetic stir bar were placed in a 250 mL round-bottom flask. The suspension was cooled to 0 °C, and lithium bis(trimethylsilyl)amide (2.24 g, 13.0 mmol) was added portionwise. The reaction mixture was then allowed to warm to room temperature over 30 minutes with stirring. A suspension of tricyclohexylphosphinodichloro(2-isopropoxybenzylidene)ruthenium(II) (Umicore® M700; 6.00 g, 10.0 mmol) in 60 mL of hexane was then added, and the reaction mixture was heated to 65 °C with stirring. After 2.5 hours, the reaction was allowed to cool to room temperature, and the precipitated solid was isolated by filtration. The crude product was washed with hexane (2 x 40 mL) and then with methanol (2 x 40 mL) and dried in vacuo.6.50 g (95% yield) of the target compound [1-(1-adamantyl)-3-(2,6-di / isopropylphenyl)-2-imidazolidinylidene]dichloro(2- / isopropoxybenzylidene)ruthenium(II) (Umicore® M726) was isolated as a green powder. State-of-the-art preparation of catalyst M726: "Decomposition Pathways of Z-Selective Ruthenium Metathesis Catalysts" Grubbs, RH et al., J. Am. Chem. Soc. 2012, 134, 18, 7861-7866 Example II.2: [1-(1-Adamantyl)-3-(2,4,6-trimethylphenyl)-2-imidazolidinylidene]-dichloro(2-isopropoxybenzylidene)ruthenium(II) M725 1-(1-Adamantyl)-3-(2,4,6-trimethylphenyl)imidazolinium tosylate (0.20 g, 0.40 mmol), hexane (2 mL), and a Teflon-coated magnetic stirrer bar were placed in a 20 mL scintillation vial. The suspension was cooled to 0 °C, and lithium bis(trimethylsilyl)amide (0.072 g, 0.43 mmol) was added portionwise. The reaction mixture was then allowed to warm to room temperature over 30 minutes with stirring. A suspension of tricyclohexylphosphinodichloro(2-isopropoxybenzylidene)ruthenium(II) (Umicore® M700; 0.20 g, 0.33 mmol) in 2 mL of hexane was then added, and the reaction mixture was heated to 65 °C with stirring. After 2.5 h, the reaction was allowed to cool to room temperature, and the precipitated solid was isolated by filtration. The crude product was washed with hexane (2 x 4 mL) and then with methanol (2 x 4 mL) and dried in vacuo.0.51 g (85% yield) of the target compound [1-(1-adamantyl)-3-(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro(2-isopropoxybenzylidene)ruthenium(II) (Umicore® M725) was isolated as a green powder. Preparation of catalyst M725 according to the state of the art: "Chelated Ruthenium Catalysts for Z-Selective Olefin Metathesis" Grubbs, RH et al., J. Am. Chem. Soc. 2011 , 133, 22, 8525-8527 Note on Example 11.1 and Example II.2: Umicore® M700 can also be added as a solid. The invention is not limited to one of the embodiments described above, but can be modified in many ways. It can be seen that the invention relates to asymmetrically 1,3-disubstituted imidazolinium salts, namely mesylates, benzenesulfonates, tosylates, and triflates. The invention also relates to a process for preparing such asymmetrically 1,3-disubstituted imidazolinium salts and their use as precursor compounds for NHC ligands. Furthermore, the invention relates to a process for preparing organometallic compounds, for example ruthenium(II) complexes, which have an asymmetrically 1,3-disubstituted NHC ligand, using imidazolinium salts of the aforementioned type. Furthermore, the invention relates to organometallic compounds, for example ruthenium(II) complexes, which have an asymmetrically 1,3-disubstituted NHC ligand and which are obtained or obtainable in particular by the aforementioned process. Using the one-pot process described here, imidazolinium salts can be obtained which do not contain halide anions and whose imidazolinium cations each bear two, particularly sterically demanding, A / substituents. The latter are an aliphatic substituent, namely a 1-adamantyl radical, and an aromatic substituent, namely a sterically less demanding unsubstituted phenyl radical or a sterically demanding substituted phenyl radical bearing at least two alkyl substituents. The aforementioned asymmetrically substituted imidazolinium salts can be prepared simply, reproducibly, and comparatively inexpensively using the one-pot synthesis presented here, in high purity, particularly free of halide anions, and in good yields of >60% or >70%. The achievable space-time yields are also satisfactory.The process can also be carried out on an industrial scale, with comparable yield and purity of the target compounds. Using the process presented here, the range of asymmetric 1,3-disubstituted imidazolinium salts of the aforementioned type, especially those with two sterically demanding ligands, can be expanded in a simple and comparatively cost-effective manner. The high purity, particularly the absence of halide anions, of the imidazolinium salts obtainable by the process described here is of particular importance with regard to their applications, for example, as organocatalysts or as NHC precursors. When these imidazolinium salts are used as NHC precursors for the synthesis of second-generation Grubbs or Hoveyc / a catalysts, undesirable anion exchange reactions are prevented. Consequently, only the desired ruthenium(II) complex is obtained. Anion exchange reactions regularly occur in the preparation of organometallic compounds, for example, the aforementioned ruthenium(II) complexes, because imidazolinium halides are commonly used as NHC precursors, sometimes even those that have different halide anions than the metal precursors or precursor complexes used. All features and advantages arising from the claims, the description and the figures, including structural details, spatial arrangements and method steps, can be essential to the invention both individually and in a wide variety of combinations.

Claims

Patent claims 1 . Process for the preparation of a compound according to the general formula 1 Formula 1 where NHC is an NHC ligand, L is a phosphine or an alkoxy group, Ar is an aromatic group bridged to L when L is an alkoxy group, by reacting a compound of formula 2 Formula 2 where L2 is a phosphine and the other definitions correspond to those of formula 1, with an NHC ligand precursor compound of the formula in which Ad is an adamantyl group or an aromatic group, Ar is an aromatic group and the NHC ligand precursor compound is reacted with a base in situ to form the free NHC ligand, which reacts with the compound of formula 2 without intermediate isolation in a one-pot reaction to form the compound of formula 1, characterized in that the process is carried out in an alkane or cycloalkane having 5 to 15 carbon atoms as solvent; lithium hexamethyldisilazide (LiHMDS) is used as the base; the compound of formula 2 is selected from the group consisting of the compounds of formulas M100, M102 and M700; M100 M102 M700 and the NHC ligand precursor compound is selected from the group consisting of the compounds of the formulas where the abbreviations of the substituents iPr stand for isopropyl, Ph for phenyl, Cy for cyclohexyl and X for Cl, tosylate and tetrafluoroborate.

2. The process according to claim 1, wherein the compound of formula 1 is selected from the group consisting of the compounds of formulas M201, M206, M725 and M726 M201 M206 3. The process according to claim 1 or 2, wherein the solvent used is a hydrocarbon selected from the group consisting of pentane, hexane, heptane, decane, dodecane and their isomers, petroleum ether and combinations thereof, in particular hexane, heptane, petroleum ether and combinations thereof.

4. The process according to one or more of claims 1 to 3, wherein the reaction of NHC ligand precursor compound with LiHMDS is carried out at a temperature of 10°C to 40°C, in particular 12°C to 25°C.

5. The process according to one or more of claims 1 to 4, wherein the reaction of NHC ligand precursor compound with LiHMDS is carried out for a time of less than five hours, in particular from 30 to 180 minutes.

6. The process according to one or more of claims 1 to 5, wherein the reaction of NHC ligand precursor compound with LiHMDS is first carried out and only then is the compound of formula 2 added.

7. Process according to one or more of claims 1 to 6, wherein the reaction of formula 2 to give the compound of formula 1 is carried out at a temperature of 40°C to 100°C, in particular 50°C to 80°C, or 60°C to 70°C.

8. Process according to one or more of claims 1 to 7, wherein the reaction of formula 2 to give the compound of formula 1 is carried out for a time of 1 to 24 hours, in particular 2 to 20 hours.

9. The method according to one or more of claims 1 to 8, wherein a cleaning step is carried out as a further method step.

10. The method of claim 9, wherein the purification step includes one or more of filtration, washing of the product, or combinations thereof.

11. A process according to claim 9 or 10, wherein the product is washed with hexane, petroleum ether, methanol or combinations thereof.

12. Process according to one or more of claims 1 to 8, wherein the reaction product, the compound of formula 1, precipitates from the solvent.

13. The process according to claim 12, wherein the reaction product, the compound of formula 1, precipitates from the solvent and has a purity of at least 95%, in particular at least 97% or 98%.

14. Compounds of formulas M725 and M726 or preparations thereof, wherein the lithium content is > 10 ppm and < 100 ppm.

15. Compounds of formulas M201, M206 or preparations thereof, wherein the lithium content is > 10 ppm and < 100 ppm.

16. Compounds according to claim 14 or 15 having a purity of 98% or greater.

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