CN101775043A - Method for synthesizing second generation Grubbs catalyst - Google Patents

Abstract

The invention discloses a method for synthesizing a second generation Grubbs catalyst, which relates to a catalyst, in particular to a metal carbine compound (H2IMes)(PCy3)(Cl)2Ru=CHPh(H2IMes is 1,3-di-(2,4,6-trimethylphenyl)imidazole alkyl, and PCy3 is tricyclohexyl phosphine) with favorable olefin double-decomposition catalytic activity, namely the second generation Grubbs catalyst. The method comprises the following step of reacting a zero valence ruthenium compound Ru(p-cymene)(COD)(p-cymene is paracymene, and COD is 1,5-cyclooctadiene) with PCy3, PhCHCL2 and a nitrogen heterocyclic carbine compound in toluene or other hydrocarbon solvents to obtain the second generation Grubbs catalyst. The invention has low cost and easy acquisition of used raw materials, simple and safe operation process, easy control and high yield and is particularly suitable for industrialized large production.

Description

The synthetic method of the second generation Grubbs catalyst

technical field

The present invention relates to a catalyst, in particular to a metal carbene compound (H ₂ IMes)(PCy ₃ )(Cl) ₂ Ru=CHPh(H ₂ IMes is 1,3-di- (2,4,6-trimethylphenyl)imidazolidine; PCy ₃ is tricyclohexylphosphine), the synthetic method of the second generation Grubbs catalyst (Ma Yuguo, University Chemistry, 2006, 21, 1).

Background technique

Olefin metathesis is one of the most important and useful types of reactions in organic chemistry. This reaction enables the coupling of normally chemically inert double bonds to each other, which greatly expands people's imagination space when constructing compound skeletons. At the same time, because the reaction has the characteristics of mild reaction conditions and high yield, and most of the organic groups do not need to be protected in this reaction, it has received extensive attention from academia and industry in recent years.

Metallocarbenes, a class of metal-carbon double bond (M=C)-containing metal-alkylene compounds, have attracted attention because of their efficient catalysis of various types of olefin metathesis reactions. Among these metal carbene metathesis catalysts, Grubbs catalysts have received special attention. The first-generation Grubbs catalyst RuCl ₂ (=CHPh)(Cy ₃ ) _2, which came out in 1995, not only has good functional group tolerance for the reaction substrate, but also has obvious stability to the water vapor and air in the reaction system, and is suitable for Normal operation in the laboratory, but it lacks satisfactory reactivity. The second-generation Grubbs catalyst (H ₂ IMes)(PCy ₃ )(Cl) ₂ Ru=CHPh developed in 1999 not only possesses all the advantages of the first-generation catalyst, but also improves its reactivity to almost perfect It has high commercial application value.

Although the second-generation Grubbs catalyst (H ₂ IMes)(PCy ₃ )(Cl) ₂ Ru=CHPh has such an important application in the field of organic synthetic chemistry, its synthesis method is currently limited to one method, that is, by using the first-generation Ligand substitution reaction of Grubbs catalysts Synthesis of second generation Grubbs catalysts (Scholl, M.; Ding, S.; Lee, CW; Grubbs, RHOrg. Lett. 1999, 1, 953).

Contents of the invention

The object of the present invention aims to provide a kind of cheap and easily prepared zero-valent ruthenium compound Ru(p-cymene) (COD) as raw material, and synthesize the second generation Grubbs catalyst ( _H2 IMes)(PCy ₃ )(Cl) ₂ Ru=CHPh method.

Concrete synthetic route of the present invention is as follows:

Its specific synthetic steps are as follows:

1) Compound H ₂ IMes(H)(Cl) (1,3-bis-(2,4,6-trimethylphenyl)-2-chloroimidazolidine) or compound H ₂ IMes(H)(BF ₄ ) (1,3-bis-(2,4,6-trimethylphenyl)-2-tetrafluoroborate imidazolidine) reacted with KNSi(CH ₃ ) ₃ in a solvent, then filtered, concentrated, Compound H ₂ Imes was obtained after crystallization, washing and drying;

2) The compound H ₂ IMes was reacted with Ru(p-cymene)(COD), PhCHCl ₂ , PCy ₃ in a hydrocarbon solvent, and then the compound (H ₂ IMes )(PCy ₃ )(Cl) ₂ Ru=CHPh, namely the second generation Grubbs catalyst.

In step 1), the compound H ₂ IMes(H)(Cl) (1,3-bis-(2,4,6-trimethylphenyl)-2-chloroimidazolidine) is preferably 0.40 g , 1.16mmol, the compound H ₂ IMes(H)(BF ₄ ) (1,3-bis-(2,4,6-trimethylphenyl)-2-tetrafluoroboratoimidazolidine) is preferably 0.46g, 1.16mmol, the KNSi(CH ₃ ) ₃ is preferably 0.53mL, 1.16mmol; the solvent is preferably tetrahydrofuran or n-hexane; the reaction time is preferably 0.5-2h.

In step 2), the compound H ₂ Imes is preferably 181mg, 0.59mmol, and the Ru(p-cymene)(COD) is preferably 200mg, 0.59mmol, and the Ru(p-cymene)(COD) Among them, p-cymene is p-cymene, COD is 1,5-cyclooctadiene; the _PhCHCl is preferably 0.10mL, 0.79mmol, and the _PCy is preferably 165mg, 0.59mmol; The hydrocarbon solvent is preferably selected from pentane, n-hexane, heptane, benzene or toluene, etc.; the reaction temperature is preferably 20-80° C., and the reaction time is preferably 12-48 hours.

Compared with the synthetic method of existing second-generation Grubbs catalyst, the present invention has the following outstanding advantages:

The present invention uses the easily synthesized zero-valent ruthenium compound Ru(p-cymene) (COD) as a raw material to efficiently synthesize the second-generation Grubbs catalyst (H ₂ IMes)(PCy ₃ )(Cl) ₂ Ru=CHPh. The reagents used in each step are cheap and easy to obtain, the operation process is simple, safe and easy to control, and the overall yield is good. It is a second-generation Grubbs catalyst (H ₂ IMes)(PCy ₃ )(Cl ) ₂ Ru=CHPh method.

Description of drawings

Fig. 1 is the ³¹ P{H} NMR spectrum of (H ₂ IMes)(PCy ₃ )(Cl) ₂ Ru=CHPh. In Fig. 1, the abscissa is the chemical shift (ppm); the nuclear magnetic resonance frequency is 162.0 MHz, the deuterated reagent used for detection is C ₆ D ₆ , and the chemical shift is 29.19 ppm.

Fig. 2 is the ¹ H NMR spectrum of (H ₂ IMes)(PCy ₃ )(Cl) ₂ Ru=CHPh. In Fig. 1, the abscissa is the chemical shift (ppm); the nuclear magnetic resonance frequency is 400.1 MHz, and the deuterated reagent used for detection is C ₆ D ₆ .

Detailed ways

The following examples further illustrate the present invention. Unless otherwise stated, all the following experimental steps were carried out at room temperature and under anhydrous and oxygen-free conditions.

Example 1

Step 1 Synthesis of Compound H ₂ IMes 2

Add H ₂ Imes(H)(Cl) (0.40g, 1.16mmol), THF (10mL) to the reaction flask, dissolve and add KNSi(CH ₃ ) ₃ (0.53mL, 1.16mmol), stir at room temperature for 0.5h, filter After removing the residue, the filtrate was sucked dry, and the compound H ₂ IMes was obtained after vacuum drying with a yield of 83%.

Step 2 Synthesis of the second generation Grubbs catalyst (H ₂ IMes)(PCy ₃ )(Cl) ₂ Ru=CHPh 3

Add compound H ₂ IMes 2 (181mg, 0.59mmol), Ru(p-cymene)(COD) (200mg, 0.59mmol), PCy ₃ (165mg, 0.59mmol) and toluene (10mL) into the reaction flask, dissolve and add PhCHCl ₂ (0.10mL, 0.79mmol), stirred and reacted at room temperature for 30h, concentrated the solution under reduced pressure to about 1mL, added 10mL of methanol, precipitated a purple-brown solid, filtered it with a sand core, washed the solid with 3×3mL methanol, and dried in vacuo The compound (H ₂ IMes)(PCy ₃ )(Cl) ₂ Ru=CHPh3 was obtained with a yield of 50%. Figure 1 shows the ³¹ P{H}NMR spectrum of (H ₂ IMes)(PCy ₃ )(Cl) ₂ Ru=CHPh, and Figure 2 shows the spectrum of (H ₂ IMes)(PCy ₃ )(Cl) ₂ Ru=CHPh ¹ H NMR spectrum. ¹ H NMR (CDCl ₂ , 400MHz) δ19.70(s, 1H), 7.35-7.00(m, 9H), 3.46(s, 4H), 2.70-0.80(m, 51H); 31PNMR (CDCl2, 162MHz) δ29 .2(s). The actual test shows that the compound has a very wide applicability of functional groups, and is very stable. It can exist in ethanol, water and carbonic acid solution, and it will not decompose when it is exposed to the air for several weeks. It can be solved by standard organic techniques. operate. At the same time, it has better catalytic performance than the first-generation Grubbs catalyst, and the application of the second-generation Grubbs catalyst can effectively shorten the reaction time or reduce the amount of catalyst used.

Example 2

Step 1 Synthesis of Compound H ₂ IMes 2

The operation of the compound H ₂ IMes 2 was the same as that in Example 1, the reactant H ₂ IMes(H)(Cl) was changed to H ₂ Imes(H)(BF ₄ ), and the yield was 84%.

Step 2 Synthesis of the second generation Grubbs catalyst (H ₂ IMes)(PCy ₃ )(Cl) ₂ Ru=CHPh 3

The synthesis steps of the compound (H ₂ IMes)(PCy ₃ )(Cl) ₂ Ru=CHPh 3 are the same as in Example 1.

Example 3

Step 1 Synthesis of Compound H ₂ IMes 2

The operation of compound H ₂ IMes 2 was the same as that in Example 1, the solvent was changed to hexane, and the mixture was stirred at room temperature for 2 h, and the yield was 85%.

Step 2 Synthesis of the second generation Grubbs catalyst (H ₂ IMes)(PCy ₃ )(Cl) ₂ Ru=CHPh 3

The synthesis steps of the compound (H ₂ IMes)(PCy ₃ )(Cl) ₂ Ru=CHPh 3 are the same as in Example 1.

Example 4

Step 1 Synthesis of Compound H ₂ IMes 2

The operation of compound H ₂ IMes 2 is the same as that in Example 1.

Step 2 Synthesis of the second generation Grubbs catalyst (H ₂ IMes)(PCy ₃ )(Cl) ₂ Ru=CHPh 3

The synthesis steps of compound (H ₂ IMes )(PCy ₃ )(Cl) ₂ Ru=CHPh 3 were the same as in Example 1, except that the reaction was stirred at 50° C. for 12 h, and the yield was 45%.

Claims (9)

1. the synthetic method of second generation Grubbs catalyst is characterized in that its concrete synthetic route is as follows: 2. the synthetic method of second generation Grubbs catalyst as claimed in claim 1 is characterized in that concrete synthetic steps are as follows: 1) Compound H ₂ IMes(H)(Cl) (1,3-bis-(2,4,6-trimethylphenyl)-2-chloroimidazolidine) or compound H ₂ IMes(H)(BF ₄ ) (1,3-bis-(2,4,6-trimethylphenyl)-2-tetrafluoroborate imidazolidine) reacted with KNSi(CH ₃ ) ₃ in a solvent, then filtered, concentrated, Compound H2Imes was obtained after crystallization, washing and drying; 2) The compound H ₂ IMes was reacted with Ru(p-cymene)(COD), PhCHCl ₂ , PCy ₃ in a hydrocarbon solvent, and then the compound (H ₂ IMes )(PCy ₃ )(Cl) ₂ Ru=CHPh, namely the second generation Grubbs catalyst. 3. the synthetic method of second generation Grubbs catalyst as claimed in claim 2 is characterized in that in step 1), described compound H ₂ IMes(H)(Cl)(1,3-two-(2,4 , 6-trimethylphenyl)-2-chloroimidazolidine) is 0.40g, 1.16mmol, the compound H ₂ IMes(H)(BF ₄ )(1,3-bis-(2,4,6- Trimethylphenyl)-2-tetrafluoroborate imidazolidine) was 0.46 g, 1.16 mmol, and the KNSi(CH ₃ ) ₃ was 0.53 mL, 1.16 mmol. 4. the synthetic method of second generation Grubbs catalyst as claimed in claim 2 is characterized in that in step 1), described solvent is THF or normal hexane. 5. The synthetic method of the second generation Grubbs catalyst as claimed in claim 2, characterized in that in step 1), the reaction time is 0.5～2h. 6. the synthetic method of second generation Grubbs catalyst as claimed in claim 2 is characterized in that in step 2), described compound H ₂ Imes is 181mg, 0.59mmol, and described Ru(p-cymene) (COD) 200 mg, 0.59 mmol, in the Ru(p-cymene) (COD), p-cymene is p-cymene, and COD is 1,5-cyclooctadiene. 7. the synthetic method of second generation Grubbs catalyst as claimed in claim 2 is characterized in that in step 2), described PhCHCl _0.10mL , 0.79mmol, described PCy ₃ is 165mg, 0.59mmol. 8. the synthetic method of second generation Grubbs catalyst as claimed in claim 2 is characterized in that in step 2) in, described hydrocarbon solvent is selected from pentane, normal hexane, heptane, benzene or toluene. 9. The synthesis method of the second-generation Grubbs catalyst as claimed in claim 2, characterized in that in step 2), the temperature of the reaction is 20-80°C, and the reaction time is 12-48h.

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