CN100412081C - A class of cobaltocene diphosphine ligands and their preparation and application - Google Patents

Abstract

The general formula is the synthesis of a class of diphenocene cobalt cationic diphosphine ligands and its use in catalyzing the Suzuki coupling reaction in ionic liquids (reaction of bromobenzene or substituted bromobenzene and phenylboronic acid to generate biphenyl compounds) ), where R represents cyclohexyl, isopropyl or tert-butyl. After the compound reacts with palladium chloride to form a complex, it can effectively catalyze the Suzuki coupling reaction in the ionic liquid at a molar concentration of 1.0%.

Description

A class of cobaltocene diphosphine ligands and their preparation and application

Technical field:

The present invention relates to the synthesis of a class of cobaltocene diphosphine ligands and the formation of complexes with palladium chloride in ionic liquids to catalyze the Suzuki coupling reaction (reaction of bromobenzene or substituted bromobenzene with phenylboronic acid to generate biphenyls) compound reaction).

Background technique:

Organophosphine ligands are widely used to catalyze various organic reactions, but bisphosphine ligands containing cobaltocene cation structures are rare. Ionic ligands can be dissolved in ionic liquids, but insoluble in less polar organic solvents, which is beneficial to the separation of products and catalysts. The present invention designs and synthesizes a class of bisphosphine ligands containing diphenocene cobalt cation structures, and uses the phosphine ligands to form complexes with palladium chloride in ionic liquids to catalyze Suzuki coupling reactions.

Invention content:

The object of the present invention is to explore compounds with better catalytic activity, to provide a class of cobaltocene phosphine compounds and their preparation methods and their application in catalytic Suzuki coupling reactions.

A class of diphosphine ligand derivatives of diphenocene cobalt cations proposed by the present invention, its general structural formula is as follows:

In formula I, R represents cyclohexyl, isopropyl or tert-butyl.

The preparation of the compound represented by general formula I is carried out as follows:

In the above reaction formula, R represents cyclohexyl, isopropyl or tert-butyl;

NaCp means sodium acene;

n-BuLi represents n-butyllithium.

When preparing the compound represented by the above-mentioned general formula I, all reactions in the preparation process are carried out continuously under a high-purity nitrogen atmosphere, and the preparation steps are:

Step 1. Add an equivalent amount of dialkyl (dialkyl is dicyclohexyl, diisopropyl or di-tert-butyl) phosphine chloride to the newly prepared sodium acene tetrahydrofuran (THF) solution at -30°C, After stirring at room temperature for 1.5 hours, add an equivalent amount of n-butyllithium dropwise to the reaction system at -78°C, return to room temperature, and continue stirring for 1.5 hours;

Step 2, add one-half equivalent of cobalt chloride to the solution in step 1, the solution turns dark brown, and reflux overnight;

Step 2, add one-half equivalent of cobalt chloride to the solution in step 1, the solution turns dark brown, and reflux overnight;

Step 3. Cool the solution obtained in step 2 to room temperature, add one-half equivalent of hexachloroethane, the solution turns green, react for 10 minutes, remove the solvent under reduced pressure, dissolve the residue with dichloromethane, add two One equivalent of ammonium hexafluorophosphate, the compound represented by general formula I is obtained.

After the compound of formula I provided by the invention is coordinated with palladium chloride, it can efficiently catalyze the Suzuki coupling reaction in the ionic liquid.

Detailed ways:

The preparation method of the compound represented by the general formula I of the present invention will be specifically illustrated by implementing examples below.

Example 1

Preparation of 1,1'-bis(dicyclohexylphosphino)cobaltocene hexafluorophosphate (expressed as I-1)

At -30°C, add 0.021 mol of dicyclohexylphosphine chloride (ClPCy ₂ ) to the freshly prepared 0.021 mol of sodium cene tetrahydrofuran solution, and after stirring at room temperature for 1.5 hours, add 0.021 mol of n-BuLi, returned to room temperature, and continued to stir for 1.5 hours. Add 0.0105 moles of cobalt chloride, the solution turns dark brown, and reflux overnight. Cool to room temperature, add 0.013 moles of hexachloroethane, the solution turns green, react for 10 minutes, remove the solvent under reduced pressure, dissolve the residue with 50 milliliters of dichloromethane, pass through a diatomaceous earth chromatographic column, and filter off lithium chloride. Obtain a green oil; dissolve the oil with dichloromethane, add 0.0105 moles of ammonium hexafluorophosphate aqueous solution, stir for 1 hour, no precipitation occurs; add an equal volume of water to the solution, then extract with dichloromethane, combine The organic layer was dried by adding anhydrous magnesium sulfate, and the obtained solid was recrystallized with diethyl ether and dichloromethane after removing the solvent to obtain a crude product, which was separated by silica gel column chromatography to obtain 51% of compound I-1.

Elemental analysis: calculated value C% 56.20 H% 7.21

Measured value C% 56.15 H% 7.18

¹ H NMR (δ/ppm) 1.13-1.96 (m, 44H, 4Cy), 5.81 (s, 4H, Cp, 2H ³ , 2H ⁴ ), 5.97 (s, 4H, Cp, 2H ² , 2H ⁵ ). ³¹ P NMR (δ/ppm) -9.93 (s), -144.05 (quintet, J _PF = 711 Hz).

Example 2

Preparation of 1,1'-bis(diisopropylphosphino)cobaltocene hexafluorophosphate (expressed as I-2)

At -30°C, add 0.021 mol of diisopropylphosphine chloride (ClP(i-Pr) ₂ ) to the freshly prepared 0.021 mol of sodium cene tetrahydrofuran solution, stir at room temperature for 1.5 hours, then add Add 0.021 mol of n-butyllithium dropwise, return to room temperature, and continue stirring for 1.5 hours. Add 0.0105 moles of cobalt chloride, the solution turns dark brown, and reflux overnight. Cool to room temperature, add 0.013 moles of hexachloroethane, the solution turns green, react for 10 minutes, remove the solvent under reduced pressure, dissolve the residue with 50 milliliters of dichloromethane, pass through a diatomaceous earth chromatographic column, and filter off lithium chloride. Obtain a green oil; dissolve the oil with dichloromethane, add 0.0105 moles of ammonium hexafluorophosphate aqueous solution, stir for 1 hour, no precipitation occurs; add an equal volume of water to the solution, then extract with dichloromethane, combine The organic layer was dried by adding anhydrous magnesium sulfate, and the obtained solid was recrystallized with diethyl ether and dichloromethane after removing the solvent to obtain a crude product, which was separated by silica gel column chromatography to obtain 59% of compound I-2.

Elemental analysis: Calculated value C% 46.65 H% 6.41

Measured value C% 46.60 H% 6.38

¹ H NMR (δ/ppm) 1.07 (m, 24H, 8CH ₃ ), 2.05 (m, 4H, CH), 5.49 (s, 4H, Cp, 2H ³ , 2H ⁴ ), 5.76 (s, 4H, Cp, 2H ² , 2H ⁵ ). ³¹ P NMR (δ/ppm) -3.03 (s), -145.92 (quintet, J _PF = 711 Hz).

Example 3

Preparation of 1,1'-bis(di-tert-butylphosphino)cobaltocene hexafluorophosphate (expressed as I-3)

At -30°C, add 0.021 mol of di-tert-butylphosphine chloride (ClP(t-Bu) ₂ ) to the freshly prepared 0.021 mol of sodium pentanocene tetrahydrofuran solution, stir at room temperature for 1.5 hours, and then add to the reaction system at -78°C Add 0.021 mol of n-butyllithium dropwise, return to room temperature, and continue stirring for 1.5 hours. Add 0.0105 moles of cobalt chloride, the solution turns dark brown, and reflux overnight. Cool to room temperature, add 0.013 moles of hexachloroethane, the solution turns green, react for 10 minutes, remove the solvent under reduced pressure, dissolve the residue with 50 milliliters of dichloromethane, pass through a diatomaceous earth chromatographic column, and filter off lithium chloride. A green oil was obtained; the oil was dissolved in dichloromethane, and a 0.0105 mole aqueous solution of ammonium hexafluorophosphate was added, and stirred for 1 hour, but no precipitate was formed. Add an equal volume of water to the solution, then extract with dichloromethane, and combine the organic layers; add anhydrous magnesium sulfate to dry, remove the solvent, and recrystallize the resulting solid with diethyl ether and dichloromethane to obtain a crude product. Separation by silica gel column chromatography yielded 12% of compound I-3.

Elemental analysis: calculated value C% 50.17 H% 7.12

Measured value C% 50.24 H% 7.11

¹ H NMR (δ/ppm) 1.24 (s, 18H, 6CH ₃ ), 1.27 (s, 18H, 6CH ₃ ), 5.67 (s, 4H, Cp, 2H ³ , 2H ⁴ ), 5.89 (s, 4H, Cp , 2H ² , 2H ⁵ ). ³¹ P NMR (δ/ppm) 23.25 (s), -145.90 (quintet, J _PF = 711 Hz).

As can be seen from the following tests, the catalyst formed by the coordination of the compound of formula I and palladium chloride has good catalytic activity for the Suzuki coupling reaction in the ionic liquid.

Typical experiment: in the 25 milliliter round-bottom flasks that magnetron and reflux condenser are housed, add phosphine ligand (ligand), palladium chloride and ionic liquid 1-methyl-3-n-butylimidazolium hexafluorophosphate ( BMIM PF ₆ ), stirred at 110°C until the mixture turned dark brown (at least 1 hour), then added an aqueous solution of bromoarene, phenylboronic acid and sodium carbonate (the molar ratio of the three substances was 1:1.1:1.1), Heat to reflux under vigorous stirring until no peak of brominated aromatic hydrocarbons can be detected by gas chromatography; after cooling, extract the product with diethyl ether, wash with brine and distilled water three times, vacuum the diethyl ether, and pass the crude product through a silica gel column to obtain High purity product.

Example 4

Catalytic Effects of Catalysts on Different Substituted Bromobenzenes in Ionic Liquid

Under the action of the catalyst, the results of the coupling reactions of different substituted bromobenzenes and phenylboronic acid are listed in Table 1. These reactions are all catalyzed by three kinds of bisphosphine ligands. Firstly, bromobenzene was used as the substrate and 1% catalyst was used to obtain a conversion rate of 98% and an isolated yield of 92%. (No. 1). Subsequently, a series of different substituted aryl bromides were investigated, and various brominated arenes containing electron-donating groups were found, such as methyl (No.2-4) and methoxybrominated arenes (No.5-7) Both gave very high yields, and various bromoarenes containing electron-withdrawing groups, such as cyano, nitro, trifluoromethyl, acetyl bromoarene, reacted with almost quantitative products. It can also be seen that 2-bromothiophene can also be reacted to obtain a high yield product (No.17), which is difficult to occur in the catalytic system with the participation of neutral phosphine ligands. In addition, the catalytic system involving three bisphosphine ligands is also particularly effective for sterically hindered 1,3,5-trimethyl-2-bromobenzene (No.18).

Table 1

表示溴代芳烃；

表示苯基硼酸；

Indicates brominated aromatic hydrocarbons;

represents phenylboronic acid;

表示联苯类化合物

Indicates biphenyl compounds

BMIM PF ₆ stands for 1-methyl-3-n-butylimidazolium hexafluorophosphate

Claims (4)

1. A class of diphenocene cobalt cationic diphosphine ligands, characterized in that they have a structure represented by general formula I,

In formula I, R represents cyclohexyl, isopropyl or tert-butyl. 2. the preparation method of the compound represented by general formula I described in claim 1 is characterized in that, use following compound to react by following route,

In the above reaction formula, R represents cyclohexyl, isopropyl or tert-butyl; NaCp means sodium acene; n-BuLi represents n-butyllithium. 3. the preparation method of the compound represented by general formula I as claimed in claim 2, is characterized in that, all reactions of preparation process are all carried out uninterruptedly under high-purity nitrogen atmosphere, and its preparation steps are: Step 1. Add an equivalent amount of dicyclohexyl phosphine chloride, diisopropyl phosphine chloride or di-tert-butyl phosphine chloride to the freshly prepared sodium acene tetrahydrofuran solution at -30°C, and stir at room temperature for 1.5 hours. Add an equivalent amount of n-butyllithium dropwise to the reaction system at -78°C, return to room temperature, and continue stirring for 1.5 hours; Step 2, add one-half equivalent of cobalt chloride to the solution in step 1, the solution turns dark brown, and reflux overnight; Step 3. Cool the solution in step 2 to room temperature, add 1/2 equivalent of hexachloroethane, the solution turns green, react for 10 minutes, remove the solvent under reduced pressure, dissolve the residue with dichloromethane, add 1/2 One equivalent of ammonium hexafluorophosphate, the compound represented by general formula I is obtained. 4. the application of the compound represented by general formula I described in claim 1 is characterized in that, with the concentration of 1.0% mole and 1.0% mole palladium chloride heating coordination in ionic liquid, as bromobenzene in ionic liquid Or a catalyst for the reaction of substituted bromobenzene and phenylboronic acid to generate biphenyl compounds, and the reaction yields of different substrates are all ≥ 90%.