DE10121105A1 - Preparation of aryl compounds for use as liquid crystal materials or intermediates, by adding Grignard reagent to mixture of substituted aryl compound and nickel catalyst - Google Patents

Abstract

In the preparation of aryl compounds (I) by cross coupling reaction of a substituted aryl compound (II) with a Grignard reagent (III) in presence of a nickel catalyst (IV), a mixture of (II) and (IV) is dosed with (III) at the reaction temperature. Independent claims are also included for: (a) the preparation of nickel catalyst precursor materials, by charging a carrier material in presence of an aqueous solution of nickel (II) salt(s) and a base; (b) the preparation of nickel catalysts (IV'), by: (i) charging a carrier material in presence of an aqueous solution of nickel (II) salt(s) and a reducing agent; or (ii) reducing a charged carrier materials obtained as in (a); and (c) the preparation of (I) from haloaromatic compounds (II') and (III), using (IV') as catalyst.

Description

The present invention relates to a particularly favorable method of manufacture of aryl compounds by cross-coupling reaction of aryl halogen compounds with Grignard reagents in the presence of nickel catalysts, their manufacture process is also the subject of the invention.

According to Inorg. Chim. Acta 296, 164 (1999) becomes a hetero for such reactions gener nickel-on-carbon catalyst used, the aryl after its manufacture chloride and then at -78 ° C the Grignard reagent, e.g. B. 4-methoxybenzyl magnet sium chloride is added. Now slowly to room temperature and then to Reflux heated. The reaction is generally carried out in the presence of lithium bromide carried out, but this does not seem to be absolutely necessary. On The disadvantage of this procedure is the need to add the Grignard Reagent at -78 ° C. Such low temperatures are on a technical level The procedure to be carried out is almost prohibitive. Another disadvantage is that the reaction is difficult to control via heat supply or removal, which A safety-related one, especially for reactions with Grignard reagents Represents risk, because of the frequently occurring delayed start of the reaction a lot of heat can be released, the removal of which then leads to problems.

The precursor materials for the nickel-on-carbon catalysts used are excluded from air in an argon atmosphere of coal and water Nickel (II) nitrate produced and must be isolated under inert Be conditions are stored (Tetrahedron, 56, 2000, 2139-2144). Before using in the cross-coupling reactions according to the invention, the precursor Materials for the reduction of nickel in the oxidation state (0) with n-butyl Implemented lithium or methyl magnesium bromide. This is catalyst production therefore not very suitable for technical use.  

There is therefore still a need for a method for producing Aryl compounds and the catalysts suitable for this process and their precursor materials, that at technically easily realizable temperatures and can be carried out without any security risks.

A method for producing aryl compounds by cross has now been found coupling reaction of a substituted aryl compound with a Grignard reagent found under nickel catalysis, which is characterized in that substi submitted aryl compound and nickel catalyst and at reaction temperature the Grignard reagent is metered in.

The preparation of aryl compounds according to the invention by cross-coupling reaction of aryl halogen compounds with Grignard reagents using the nickel catalysts likewise according to the invention can be illustrated by the following reaction equation:

Formula (I) represents the substituted aryl compound used Formula (II) the Grignard reagent used and formula (III) the prepared Aryl compound.

In the formulas (I) and (III) Ar can, for example, for an optionally substi tuiert aromatic residue with 5 to 18 framework atoms, being as framework atoms only carbon atoms, but possibly also heteroatoms in addition to carbon atoms such as N, O and / or S atoms can be present. Are hetero-scaffold atoms in front act, their number per Ar group is, for example, 1, 2 or 3, preferred example 1 or 2. Ar preferably represents optionally substituted phenyl,  Tolyl, naphthyl, anthryl, phenanthryl, biphenyl or a 6-membered 1 to 2 Aromatic radical containing N atoms.

Possible substituents for Ar are, for example: halogen, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -haloalkoxy, tri-C ₁ -C ₆ -alkyl -siloxyl, aldehyde groups protected in the form of acetals or aminales, aryl with 6 to 10 skeletal atoms, which are only C atoms, but also 1 to 2 N, O and / or S in addition to C atoms Atoms can act, NR ' ₂ , SO ₃ R ", SO ₂ R", SOR ", SR" or POR " ₂ , where the two R' are the same or different and each represents hydrogen, C ₁ -C ₆ - Can be alkyl or C ₆ -C ₁₀ aryl, and R "can be C ₁ -C ₆ alkyl or C ₆ -C ₁₀ aryl. One or more of the same or different substituents may be present, for example up to three per Ar.

Ar is preferably carbocyclic C ₆ -C ₁₀ aryl, optionally with one or two substituents from the group C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ fluorine - or -Chloralkyl or phenyl is substituted, where one or two, the same or different ones of the substituents may be present.

Particularly preferred substituted aryl compounds are chlorotoluene and chlorobenzo nitrile, chloroanisole, chloropyridine, dichlorobenzene, chlorobiphenyl, chloronaphthalene, Chlorofluorobenzene, chlorotrifluoromethylbenzene and chloroethylbenzene.

In formula (I), X can represent, for example, chlorine, bromine or OR ¹ , where R ^{1 represents} SO ₂ R ² or CON (R ² ) ₂ with R ² = C ₁ -C ₄ alkyl or C ₁ -C ₄ -Perhaloalkyl, especially trifluoromethyl.

In the formulas (II) and (III), R can represent, for example, optionally substituted C ₁ -C ₂₆ alkyl, C ₂ -C ₁₂ alkenyl or C ₅ -C ₁₈ aryl. The alkenyl groups can, insofar as it is possible from the number of carbon atoms present, be mono- or polyunsaturated and, like the alkyl groups, not only straight-chain, but optionally also branched or cyclic or contain cyclic structures. The alkyl, alkenyl and aryl groups can optionally be substituted, for example with 1 to 5 identical or different substituents from the group as indicated above as substituents for Ar.

In formula (II), Hal represents chlorine or bromine, for example.

Particularly preferred Grignard reagents are ethyl, propyl, phenyl, tolyl and p-Methoxyphenylmagnesiumchlorid.

Based on 1 mole of Grignard reagent, 0.1 to 3 equivalents can be used, for example Use the substituted aryl compound. This amount is preferably included 0.8 to 1.5 equivalents and in particular approximately one equivalent.

The respective Grignard reagent is generally dissolved in a solution means used. Such solutions can be, for example, 15 to 40% by weight his. They are preferably 20 to 35% by weight. The Grignard reagent solution can one freshly prepared according to methods known per se.

The substituted aryl compound can also act as a solvent. Then it is necessary to use them in larger quantities, for example in quantities up to 20 Equivalents, preferably up to 10 equivalents, each per mole of Grignard Reagent.

In the nickel catalysts according to the invention it can be, for. B. Ni (O) - Act on supported catalysts that have been made by using a support material loaded with the aqueous solution of a nickel compound and the nickel compound has reduced with a reducing agent.  

As support materials such. B. activated carbon, aluminum oxides, silicon dioxide and silicates in question. The carrier material can have, for example, inner surfaces of 10 to 2000 m ² / g. Activated carbon with an inner surface of 800 to 1600 m ² / g or aluminum oxides, silicon oxides or silicates with inner surfaces of 100 to 400 m ² / g are preferably used. The solutions of a nickel compound are preferably an aqueous solution of, for example, nickel (II) chloride, bromide, acetate, nitrate or sulfate or mixtures thereof.

For example, the carrier material can be loaded such that the carrier material with an aqueous solution of one or more nickel compounds is soaked, if necessary after removal of excess solution, dried and / or is heated. The temperature can be, for example, 150 ° to 400 ° C, preferably 170 to 300 ° C. In this way, for example, nickel nitrate can be converted into nickel oxide. Another option is that of the carrier material in the presence of an aqueous solution of one or more nickel compounds is loaded and in the presence of a base. For example first of all the carrier material with an aqueous solution of one or more Nickel compounds are presented and then the base is added, but also an aqueous solution of one or more nickel compounds to an aqueous gene suspension of the carrier material and a base are given. For example is also the simultaneous dosing of base and an aqueous solution of one or several nickel compounds to form an aqueous suspension of the carrier material possible. As bases, for example, alkali metal oxides, hydroxides or Carbonates and alkaline earth metal hydroxides are used, are preferred Alkali metal hydroxides, particularly preferred are sodium hydroxide and potassium hydroxide. After drying and / or heating to 150 to 400 ° C, preferably 170 to In this way, 300 ° C. gives oxidic catalyst precursor materials which are insensitive to oxygen and therefore need to be stored under protection gas atmosphere can be dispensed with.  

The reduction can, for example, when carrying out the loading z. B. by direct addition of the reducing agent in the aqueous phase. But it can even after drying and / or heating the loaded carrier material consequences.

The nickel (O) -containing catalysts are also in the water-moist state storage stable. Before being used in the cross-coupling reak according to the invention tions should the water-moist catalysts z. B. by heating and / or on place to be vacuum dried. The advantage of the nickel Catalysts and their precussor materials is one that is based on their manufacture can dispense with organic solvents and inert conditions.

As reducing agents come in aqueous solution such. B. hydrazine and formaldehyde in question. If Ni (II) precursor materials are used in the cross coupling, then the reduction for example with organolithium compounds such as n- Butyllithium, hydrogen or in situ with the Grignard reagent used respectively.

In this case, the advantage is that the catalyst precursor materials Air are stable in storage, which makes it particularly easy to handle in the technical field considerably simplified.

The finished nickel supported catalyst or the precursor materials can, for. B. 0.5 up to 100 g nickel per kg, preferably 0.5 to 50 g nickel per kg, especially be preferably 0.5 to 10 g of nickel per kg and very particularly preferably 2 to 5 g of nickel per kg included.

Based on 1 mol of Grignard reagent, one can in the cross according to the invention coupling reaction e.g. B. use as much nickel supported catalyst that the amount from 0.001 to 0.2 moles of nickel (calculated as metal). Preferably lies this amount at 0.005 to 0.05 moles.  

The method according to the invention can, for. B. perform so that the sub substituted aryl compound, the nickel catalyst and optionally to be used Solvent, for example at 0 to 25 ° C, then this mixture on Reak temperature, for example to 0 to 150 ° C and then the Grignard Added reagent.

It is an essential feature of the present invention that the Grignard Reagent metered in at the reaction temperature and not the total amount as before Grignard reagent is added at low temperature and then the reaction temperature from lower temperatures.

The reaction temperature is preferably 20 to 120 ° C., in particular 35 to 100 ° C.

The method according to the invention can also be carried out in such a way that only one Part of the substituted aryl compound intended for use (e.g. 20 to almost 100%) with the nickel catalyst and any solution to be used medium and the rest of the aryl compound during the dosing of Grignard reagent.

After the addition of the Grignard reagent has ended, a few more can be done Time at z. B. stir 0 to 150 ° C.

If you want to work at temperatures that are above boiling at normal pressure point of a component of the reaction mixture can also be under pressure work. It is preferred to work at normal pressure at reflux or in ge closed vessel in which set itself at the respective temperature the pressure.  

As solvents for the process according to the invention, for. B. aromatic Solvents such as mono- and polyalkylbenzenes and ethers such as diethyl ether, tert.- Butyl methyl ether and tetrahydrofuran in question. Tetrahydrofuran is preferred. How An excess of substituted aryl compound as Lö can also be mentioned above serve means.

In a special embodiment of the method according to the invention works one additionally in the presence of a phosphorus-containing component. With this it can z. B. is an organic phosphorus compound, in particular di- or triaryl and alkyl phosphines and phosphites. Individual examples of phosphorus components containing triphenylphosphine, triphenylphosphite, tritolylphosphine, Bis (diphenylphosphino) ethane, 1,4-bis (diphenylphosphino) butane, 1,3-bis (tri phenylphosphino) propane, tri-tert-butylphosphine, tricyclohexylphosphine and tris (2,4-di-tert-butylphenyl) phosphite.

If you use a phosphorus-containing component, you can get from it to 1 mol of nickel in the catalyst, for example 0.1 to 20 mol. With the The addition of a phosphorus-containing component can often result in a higher reaction achieve speeds and / or better selectivities.

For working up, the reaction mixture can, for example, with water or an alcohol, for. B. a C ₁ -C ₄ alkyl alcohol, filter off the solid components and z. B. wash with the solvent used in the reaction. The filtrate and the washing liquids can then be combined and the solvents contained therein removed. Distillation of the residue under high vacuum can then the aryl compound prepared in general in yields of over 85%. Th. And deliver in purities of over 95%.

The catalyst used can be recovered, for example, by the reaction mixture after the end of the reaction and before the addition of Filtered water or alcohol and washes the catalyst isolated in this way, e.g. B. with  Water, and dries. He can then re-enter the method according to the invention used or used in any other way.

Such compounds as can be produced according to the invention are suitable z. B. for use as liquid crystalline materials and as precursors for such materials. They also provide intermediate products for pharmaceuticals, agricultural products substances (e.g. fungicides and herbicides), pigments and varnishes.

The process according to the invention has the advantage that the reaction is carried out can control by dosing the Grignard reagent. This response control is simple and safe in terms of safety. It was not foreseeable that this change in the procedure without disadvantages with regard to the reacti vity and selectivity of the catalyst can be realized. In the invention The process is the concentration of the Grignard reagent in the reaction mixture throughout at a very low level, while according to the state of the art too At the start of the reaction the Grignard reagent is present in high concentration then decreases continuously. The concentration of a reactant in the reak is known to have a very strong influence on the flow of Reactions.

Furthermore, the method according to the invention has the advantage that without the An using low temperatures.  

Examples Production of supported nickel catalysts to be used according to the invention example 1

98 g of an activated carbon with an inner surface area of 1600 m ² / g were mixed with a solution of 9.1 g of Ni (NO ₃ ) ₂ × 6 H ₂ O in 100 ml of water for 30 minutes. The mixture was dried in a stream of nitrogen at 100 ° C. and then annealed at 170 ° C. for 1 hour. The solid was then reduced to 450 ° C. in the water stream.

Example 2

98 g of an activated carbon with an inner surface area of 1600 m ² / g were mixed with a solution of 9.1 g of Ni (NO ₃ ) ₂ × 6 H ₂ O in 100 ml of water for 30 minutes. The mixture was dried in air at 100 ° C and then annealed at 170 ° C for 1 hour.

Examples 3 to 5

98 g of a carrier were slurried in 600 ml of water, a solution of 8.1 g of NiCl ₂ × 6 H ₂ O in 50 ml of water was added and the mixture was stirred for a further 30 minutes. The pH was then adjusted to 10 using a 5% strength aqueous sodium hydroxide solution and the mixture was subsequently stirred for 1 hour. The catalyst was filtered off, washed free of chloride with water and then dried in vacuo at 100 ° C. for 1 hour.

The supports in Example 3 were activated carbon with an inner surface (BET) of 800 m ² / g, in Example 4 silicon dioxide with an inner surface (BET) of 300 m ² / g and in Example 5 with aluminum oxide an inner surface area (BET) of 150 m ² / g.

Coupling reactions according to the invention Example 6

0.75 g of the catalyst from Example 1 were introduced under nitrogen, 0.52 g of tri phenylphosphine, 3.26 g 3-chlorotoluene (97%) in 15 ml absolute tetrahydrofuran (THF) added and heated to 50 ° C. At 50 ° C were within 2 hours Stir in 13.8 ml of a 2 molar solution of phenylmagnesium chloride in THF dripped. The mixture was then boiled under reflux for 12 hours. After the Ab Cool to room temperature, 10 ml of ethanol were added, the reaction filtered mixture, the filter cake washed with THF and the filtrate concentrated. The residue was distilled in a high vacuum. This gave 3.6 g of 3-methylbiphenyl (83% of theory, purity 97%).

Example 7

0.75 g of the catalyst from Example 1 were introduced under nitrogen, 0.52 g of tri phenylphosphane, 3.26 g of 3-chlorotoluene in 15 ml of THF and reflux heated. At reflux, 25 ml of a 2-mo laren solution of phenyl magnesium chloride in THF added dropwise. Then was Cooked under reflux for 12 hours. After cooling to room temperature 10 ml of ethanol were added, the reaction mixture was filtered and the filter cake washed with THF and the filtrate was concentrated. The backlog was high vacuum distilled. This gave 4.1 g of 3-methylbiphenyl (96% of theory, purity 98%).

Example 8

The procedure was as in Example 6, but without the addition of triphenylphosphine. It 2.85 g of 3-methylbiphenyl with a purity of 96% were obtained. The corresponds to a yield of 65% of theory. Th.  

Example 9

The procedure was analogous to Example 6, but with 4-chloroanisole (25 mmol) as Reactant. 4.0 g of 3-methoxybiphenyl with a purity of 98% were obtained. This corresponds to a yield of 85% of theory. Th.

Example 10

The procedure was analogous to Example 6, but using the catalyst from Example 5. 3.8 g of 3-methylbiphenyl in a purity of 97% receive. This corresponds to a yield of 88% of theory. Th.

Example 11

The procedure was analogous to Example 7, but instead of triphenylphosphine Triphenyl phosphite used. 3.3 g of 3-methylbiphenyl with a purity of 94% received. This corresponds to a yield of 74% of theory. Th.

Example 12

The procedure was as in Example 6, but using the catalyst Example 2. 3.7 g of 3-methylbiphenyl with a purity of 97% were obtained. The corresponds to a yield of 85% of theory. Th.

Example 13

Under an argon atmosphere, 0.75 g of the catalyst obtained according to Example 1 Sators submitted, first 0.52 g triphenylphosphine and then 3.26 g 3-chlorotoluene (97%) dissolved in a mixture of 5 ml of THF and 10 ml of toluene. The Mixture was heated to reflux and held. It was within 3 hours  with stirring, 13.8 ml of a 2 molar solution of phenylmagnesium chloride in THF added dropwise and stirred for a further 3 hours. After cooling to room 3 ml of water were slowly added with cooling and the catalyst filtered off. The filtrate was separated between water / toluene and the orga African phase concentrated. The remaining residue was distilled under high vacuum profiled. This gave 3.7 g of 3-methylbiphenyl with a purity of 97%. The corresponds to a yield of 85% of theory. Th.

Example 14

Example 13 was carried out with the catalyst from Example 3. There were 3.8 g 3-Methylbiphenyl obtained with a purity of 95%. That corresponds to one Yield of 86% of theory Th.

Example 15

Example 13 was with the starting materials 4-chloroanisole and 4-tolylmagnesium chloride carried out. 4.2 g of 4-methoxy-4'-methylbiphenyl with a purity of 95% received. This corresponds to a yield of 80% of theory. Th.

Example 16

Example 13 was carried out with the catalyst from Example 4. There were 3.5 g Obtained 3-methylbiphenyl with a purity of 94%. That corresponds to one Yield of 78% of theory Th.

Example 17

Under an argon atmosphere, 0.75 g of the catalyst obtained according to Example 1 sators and 0.52 g of triphenylphosphine and suspended in 10 ml of THF. The Suspension was brought to 65 ° C. with stirring and 3.26 g of 3-chlorotoluene (97%,  25 mmol) within 1 hour and 13.8 ml of a 2 molar solution of Phenylmagne sodium chloride in THF added dropwise in parallel within 2 hours. Then 5 Stirred at 65 ° C for hours. After working up according to Example 18 3.9 g of 3-methylbiphenyl obtained in a purity of 97%. That corresponds to one Yield of 90% of theory Th.

Claims (17)

1. A process for the preparation of aryl compounds by cross-coupling reaction of a substituted aryl compound with a Grignard reagent under nickel catalysis, characterized in that substituted aryl compound and nickel catalyst are initially introduced and the Grignard reagent is metered in at the reaction temperature. 2. The method according to claim 1, characterized in that the substituted aryl compound of formula (I) to be used corresponds to the Grignard reagent of formula (II) and the aryl compound of formula (III) to be used,
where in the formulas (I) and (III) Ar stands for an optionally substituted aromatic radical of up to 5 to 18 skeleton atoms, where only carbon atoms or heteroatoms in addition to carbon atoms can be present as skeleton atoms,
where the substituents optionally present on Ar are halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ haloalkoxy, tri-C ₁ - C ₆ alkyl -siloxyl, in the form of acetals or animals protected aldehyde groups, aryl with 6 to 10 framework atoms, NR ' ₂ , SO ₃ R ", SO ₂ R", SOR ", SR" or POR " _{2 can} mean, the framework atoms in Aryl can only be C atoms or in addition to C atoms around N, O and / or S atoms and where the two R 'can be the same or different and each represents hydrogen, C ₁ -C ₆ alkyl or C ₆ -C ₁₀ aryl, and where R "is C ₁ -C ₆ alkyl or C ₆ -C ₁₀ aryl,
in the formulas (II) and (III) for R are optionally substituted C ₁ -C ₂₆ alkyl, C ₂ -C ₁₂ alkenyl or C ₅ -C ₁₈ aryl, the substituents being the same as for the rest Ar and
in formula (II) Hal represents chlorine or bromine. 3. The method according to claim 2, characterized in that one as a verb of the formula (I) chlorotoluene, chlorobenzonitrile, chloranisole, chloropyridine, Dichlorobenzene, chlorobiphenyl, chloronaphthalene, chlorofluorobenzene or chlorine trifluoromethylbenzene and as a compound of formula (II) ethyl, propyl, Phenyl, tolyl or p-methoxyphenyl magnesium chloride is used. 4. The method according to claims 1 to 3, characterized in that be drew 0.1 to 3 equivalents of the substituted on 1 mole of Grignard reagent Aryl compound used. 5. The method according to claims 1 to 5, characterized in that one 1 mol of Grignard reagent uses as much nickel supported catalyst that the Amount of 0.01 to 0.2 moles of nickel (calculated as metal) corresponds. 6. The method according to claims 1 to 6, characterized in that it at Performs temperatures in the range of 0 to 150 ° C. 7. The method according to claims 1 to 7, characterized in that it at Performs 35 to 100 ° C. 8. The method according to claims 1 to 8, characterized in that sub substituted aryl compound, nickel catalyst and optionally used the solvent at 0 to 25 ° C, then this mixture on Reak brings temperature and then dosed the Grignard reagent.   9. The method according to claims 1 to 9, characterized in that only with a part of the substituted aryl compound intended for use the nickel catalyst and any solvents to be used and adds the rest while dispensing the Grignard reagent. 10. Process for the production of precursor materials for nickel catalysts, characterized in that a carrier material in the presence of an aqueous load solution of one or more nickel (II) salts and a base becomes. 11. The method according to claim 10, characterized in that the loaded Carrier material is heated to 150 to 400 ° C. 12. The method according to claim 10, characterized in that the loaded Carrier material is heated to 170 to 300 ° C. 13. A process for the production of nickel catalysts, characterized in that that a carrier material in the presence of an aqueous solution or several nickel (II) salts and a reducing agent is loaded. 14. The method according to claim 13, characterized in that the reduction contains hydrazine or formaldehyde. 15. A process for the production of nickel catalysts, characterized in that that a loaded carrier material according to claims 10 to 12 by Adding a reducing agent can be reduced. 16. The method according to claim 15, characterized in that the reduction with hydrogen, organolithium compounds or a Grignard reagent he follows.   17. Process for the preparation of aryl compounds from halogen aromatics and Grignard compounds, characterized in that nickel catalyst ren according to one or more of claims 13 to 16.