Process for the preparation of a cyclopentadiene derivative

Abstract

The application discloses a preparation method of a cyclopentadiene derivative, which comprises the following steps: (1) uniformly mixing silica gel with a polymerization inhibitor, a dehydration catalyst and a solvent, and drying to obtain loaded silica gel; (2) sequentially adding the loaded silica gel and molecular sieve into a filler column to form a loaded silica gel layer and a molecular sieve layer in the filler column, and horizontally placing the filled filler column, wherein one end of the filler column close to the loaded silica gel layer is a feeding port, and the other end is a discharging port; (3) adding a cyclopentadiene alcohol derivative solution and an alkane solvent from the feeding port, maintaining negative pressure at the discharging port, and collecting the mixed solution flowing out of the discharging port; and (4) performing concentration treatment on the mixed solution collected in the step (3), and obtaining the cyclopentadiene derivative after removing the solvent. The preparation method can effectively improve the conversion rate of reactants and effectively inhibit the self-polymerization of products, and high-purity products can be obtained without purification, and the yield can be up to 83% or more.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, and more specifically to a method for preparing a cyclopentadiene derivative. Background Technology

[0002] Cyclopentadiene and its derivatives are important chemical raw materials widely used in the preparation of metallocene compounds. Common metallocene compounds include ferrocene(II), bis(ethylcyclopentadienyl)ruthenium(II), bis(pentamethylcyclopentadienyl)ruthenium(II), and bis(tetramethylcyclopentadienyl)zirconium(IV), etc. The synthesis of these metallocene compounds is inseparable from cyclopentadiene and its derivatives.

[0003] Taking tetramethylcyclopentadiene as an example, the traditional synthesis method involves reducing tetramethylcyclopentenone to tetramethylcyclopentenol using lithium aluminum hydride, followed by catalytic dehydration with p-toluenesulfonic acid to obtain tetramethylcyclopentadiene. In the second step of catalytic dehydration, two major problems are often encountered: insufficient feed conversion and product self-polymerization. Specifically, the water and diethyl ether produced in this step are immiscible, while p-toluenesulfonic acid has a much higher solubility in water than diethyl ether. This leads to a large amount of catalyst being distributed in the aqueous phase, reducing the effective catalyst concentration in the organic phase and making it difficult for the reaction to continue, ultimately resulting in a feed conversion rate between 75% and 85%. Although extending the reaction time, adding p-toluenesulfonic acid, and appropriate heating can help further improve the conversion rate, these measures accelerate the self-polymerization of the product, severely affecting the yield.

[0004] Therefore, there is an urgent need for a method to prepare cyclopentadiene derivatives that can improve the conversion rate of raw materials while effectively avoiding product self-polymerization. Summary of the Invention

[0005] This invention provides a method for preparing cyclopentadiene derivatives. A reaction device is constructed by filling a packed column with silica gel supported on a catalyst and a polymerization inhibitor and a molecular sieve. The cyclopentadiene derivative is prepared by this reaction device, which can effectively improve the conversion rate of the raw material cyclopentadienol derivative, and at the same time effectively avoid the self-polymerization of the product cyclopentadiene derivative. High-purity products can be obtained without purification, and the yield can be as high as 83% or more.

[0006] To solve the above-mentioned technical problems, the present invention provides the following technical solution:

[0007] This invention provides a method for preparing a cyclopentadiene derivative, comprising the following steps:

[0008] (1) Mix silica gel with polymerization inhibitor, dehydration catalyst and solvent evenly, and dry to obtain loaded silica gel;

[0009] (2) The loaded silica gel and molecular sieve are added to the packing column in sequence to form a loaded silica gel layer and a molecular sieve layer in the packing column; and the filled packing column is placed horizontally, with one end of the packing column near the loaded silica gel layer as the feed port and the other end as the discharge port.

[0010] (3) Dissolve the cyclopentadienol derivative shown in formula (I) in an ether solvent to obtain a cyclopentadienol derivative solution. Then add the cyclopentadienol derivative solution and the alkane solvent one after the other from the feed inlet of the packing column, and maintain the negative pressure at the outlet to collect the mixed solution flowing out of the outlet.

[0011] (4) The mixed solution collected in step (3) is concentrated and the solvent is removed to obtain the cyclopentadiene derivative shown in formula (II);

[0012] The structures of equations (I) and (II) above are shown below:

[0013]

[0014] R1, R2, R3, R4, and R5 are each independently selected from H and C1 to C20 alkyl groups.

[0015] Further, in step (1), the silica gel is 300-400 mesh chromatography silica gel.

[0016] Further, in step (1), the polymerization inhibitor is selected from one or more of 2,6-di-tert-butyl-p-cresol, p-cresol, and hydroquinone.

[0017] Further, in step (1), the dehydration catalyst is selected from one or more of p-toluenesulfonic acid, p-nitrobenzenesulfonic acid, benzenesulfonic acid, and hydrochloric acid.

[0018] Further, in step (1), the mass ratio of the silica gel to the polymerization inhibitor and the dehydration catalyst is 100:0.05-0.2:0.5-2. For example, in some preferred embodiments, the mass ratio is 100:0.1:1.

[0019] Further, in step (1), the solvent is selected from one or more of diethyl ether, n-pentane, n-hexane, methyl tert-butyl ether, and isopropyl ether.

[0020] Further, in step (2), the thickness ratio of the loaded silica layer to the molecular sieve layer is 1:1-10.

[0021] Furthermore, in step (2), the packing column is made of glass, 316 stainless steel or polypropylene.

[0022] Further, in step (3), the ether solvent is one or more of diethyl ether, methyl tert-butyl ether, and isopropyl ether.

[0023] Further, in step (3), the molar ratio of the cyclopentadienol derivative to the dehydration catalyst in the cyclopentadienol derivative solution is 20-100:1, for example, 20:1, 25:1, 30:1, 35:1, 40:1, 45:1, 50:1, 60:1, 70:1, 80:1, 90:1, 100:1, etc., including but not limited to the molar ratios listed above.

[0024] Furthermore, in step (3), the alkane solvent is selected from one or more of n-pentane, n-hexane, and n-heptane.

[0025] Furthermore, in step (3), the collection is stopped after the solution flowing out of the outlet is confirmed by GC-MS to have no product.

[0026] Furthermore, in step (4), the pressure of the negative pressure is 10-80 kPa.

[0027] Furthermore, the cyclopentadiene derivatives include, but are not limited to, tetramethylcyclopentadiene and pentamethylcyclopentadiene; that is, R1-R4 are methyl and R5 is H or methyl.

[0028] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0029] 1. Addressing the issues of insufficient raw material conversion and product self-polymerization in existing cyclopentadiene derivative preparation processes, this invention constructs a reaction device by filling a packed column with silica gel supported by a catalyst and polymerization inhibitor, along with a molecular sieve. The reactants are introduced into the packed column through an inlet near the supported silica gel, while a negative pressure is applied to the outlet to ensure material flow from the inlet to the outlet. As the reactant flows through the supported silica gel, it undergoes catalytic dehydration to generate the product. The product remains stable under the action of the polymerization inhibitor, effectively reducing the risk of product self-polymerization. After elution with an alkane solvent, the product is further purified by adsorbing water using a molecular sieve to obtain a mixed solution containing the product. Concentration and solvent removal yield the final product. This reaction device is simple, highly adaptable, and can increase the raw material conversion rate to 98%, effectively reducing the risk of product self-polymerization. The liquid collected at the outlet can be directly concentrated to obtain a high-purity product.

[0030] 2. The method described in this invention is simple to operate and has high reaction efficiency. The yield of the target product can be as high as 83% or more, and the product with a purity of up to 99.9% can be obtained without post-processing or purification. Attached Figure Description

[0031] Figure 1This is a schematic diagram of the packing column of the reaction device, where ① is the loaded silica gel, ② is the molecular sieve, ③ is the feed inlet, and ④ is the discharge outlet. Detailed Implementation

[0032] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the specification of this invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items. "Comprising" or "containing" as used herein means that it may include or contain other components in addition to the stated components. "Comprising" or "containing" as used herein may also be replaced with the closed form "is" or "consisting of".

[0033] As described in the background section, the current preparation process of cyclopentadiene and its derivatives suffers from problems such as insufficient raw material conversion and product self-polymerization, resulting in complex purification processes and low yields.

[0034] To address the aforementioned technical problems, embodiments of the present invention provide a method for preparing a cyclopentadiene derivative, comprising the following steps:

[0035] (1) Mix silica gel with polymerization inhibitor, dehydration catalyst and solvent evenly, and dry to obtain loaded silica gel;

[0036] (2) The loaded silica gel and molecular sieve are added sequentially to the packed column to form a loaded silica gel layer and a molecular sieve layer in the packed column; the packed column is then placed horizontally, with the end of the packed column closest to the loaded silica gel layer as the inlet and the other end as the outlet. Figure 1 As shown;

[0037] (3) Dissolve the cyclopentadienol derivative shown in formula (I) in an ether solvent to obtain a cyclopentadienol derivative solution. Then add the cyclopentadienol derivative solution and the alkane solvent one after the other from the feed inlet of the packing column, and maintain the negative pressure at the outlet to collect the mixed solution flowing out of the outlet.

[0038] (4) The mixed solution collected in step (3) is concentrated and the solvent is removed to obtain the cyclopentadiene derivative shown in formula (II);

[0039] The structures of equations (I) and (II) above are shown below:

[0040]

[0041] R1, R2, R3, R4, and R5 are each independently selected from H and C1 to C20 alkyl groups.

[0042] Addressing the issues of insufficient raw material conversion and product self-polymerization in existing cyclopentadiene derivative preparation processes, this invention constructs a reaction apparatus by filling a packed column with silica gel supported by a catalyst and polymerization inhibitor, along with a molecular sieve. The reactants are introduced into the packed column through an inlet near the supported silica gel, while a negative pressure is applied to the outlet to ensure material flow from the inlet to the outlet. As the reactant flows through the supported silica gel, it undergoes catalytic dehydration to generate the product. The product remains stable under the action of the polymerization inhibitor, effectively reducing the risk of product self-polymerization. After eluting the product with an alkane solvent, water is adsorbed through a molecular sieve to obtain a mixed solution containing the product. The solution is then concentrated to remove the solvent, yielding the final product. This reaction apparatus effectively improves the raw material conversion rate and reduces the risk of product self-polymerization, eliminating the need for further purification and achieving high-purity, high-yield products.

[0043] In some preferred embodiments of the present invention, the silica gel may be 300-400 mesh chromatography silica gel, but the present invention does not limit the type of silica gel.

[0044] In some preferred embodiments of the present invention, the polymerization inhibitor can be selected from one or more of 2,6-di-tert-butyl-p-cresol, p-cresol, and hydroquinone. By modifying the surface of the silica gel with the polymerization inhibitor, the self-polymerization of the product is effectively reduced, and the yield is improved. In addition, the dehydration catalyst can be selected from one or more of p-toluenesulfonic acid, p-nitrobenzenesulfonic acid, benzenesulfonic acid, and hydrochloric acid. By modifying the surface of the silica gel with the dehydration catalyst, the reactants can be dehydrated under its action to generate the product, while effectively avoiding a large amount of dehydration catalyst dissolving in water, thus not affecting the reaction and improving the conversion rate of the reactants.

[0045] More specifically, the mass ratio of the aforementioned silica gel to the polymerization inhibitor and dehydration catalyst is 100:0.05-0.2:0.5-2, for example, a mass ratio of 100:0.1:1.

[0046] In some preferred embodiments of the present invention, in step (1), the solvent is selected from one or more of diethyl ether, n-pentane, n-hexane, methyl tert-butyl ether, and isopropyl ether.

[0047] In some preferred embodiments of the present invention, the layer thickness ratio of the loaded silica layer to the molecular sieve layer in the packed column is 1:1-10, such as 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, etc., including but not limited to the layer thickness ratios listed above; by adjusting the layer thickness of the loaded silica layer and the molecular sieve layer, the reaction can proceed fully while water in the product can be effectively removed.

[0048] In some preferred embodiments of the present invention, the packing column may be made of glass, 316 stainless steel or polypropylene, but is not limited to these materials, as long as it has good acid and alkali resistance and does not react with reactants or products.

[0049] In some preferred embodiments of the present invention, in step (3), the ether solvent may be one or more of diethyl ether, methyl tert-butyl ether, and isopropyl ether.

[0050] In some preferred embodiments of the present invention, the molar ratio of the cyclopentadienol derivative to the dehydration catalyst added in step (1) in the cyclopentadienol derivative solution is 20-100:1, for example 20:1, 25:1, 30:1, 35:1, 40:1, 45:1, 50:1, 60:1, 70:1, 80:1, 90:1, 100:1, etc., including but not limited to the molar ratios listed above.

[0051] In some preferred embodiments of the present invention, the alkane solvent is selected from one or more of n-pentane, n-hexane, and n-heptane.

[0052] In some preferred embodiments of the present invention, collection is stopped after the solution flowing out of the outlet is confirmed by GC-MS to have no product.

[0053] In some preferred embodiments of the present invention, the negative pressure at the discharge port is 10-80 kPa, such as 10 kPa, 20 kPa, 30 kPa, 40 kPa, 50 kPa, 60 kPa, 70 kPa, 80 kPa, etc., including but not limited to the negative pressures listed above. The negative pressure at the discharge port should not be too high, as excessive pressure, such as greater than 80 kPa, will lead to a slow flow rate, thus affecting the reaction efficiency; however, the pressure should not be too low, such as less than 10 kPa, as this will lead to excessively rapid product evaporation, affecting the yield. Therefore, the negative pressure at the discharge port needs to be controlled within a suitable range to improve the reaction efficiency without affecting the yield.

[0054] In some preferred embodiments of the present invention, the cyclopentadiene derivatives include, but are not limited to, tetramethylcyclopentadiene and pentamethylcyclopentadiene.

[0055] The present invention will be further described below with reference to specific embodiments, so that those skilled in the art can better understand and implement the present invention, but the embodiments are not intended to limit the present invention.

[0056] Example 1

[0057] This embodiment provides a method for synthesizing tetramethylcyclopentadiene, as detailed below:

[0058] (1) Weigh 861 mg (5 mmol) of p-toluenesulfonic acid, 86.1 mg of 2,6-di-tert-butyl-p-cresol, 86.1 g of silica gel, and 43 g of diethyl ether, mix them evenly, and evaporate the solvent to obtain loaded silica gel.

[0059] (2) The loaded silica gel and molecular sieve prepared in step (1) are loaded into a packing column to form a loaded silica gel layer and a molecular sieve layer in the packing column. The thickness ratio of the loaded silica gel layer to the molecular sieve layer is 1:2. The filled packing column is placed horizontally, with one end of the packing column near the loaded silica gel layer as the inlet and the other end as the outlet.

[0060] (3) Weigh 14.2g (100mmol) of tetramethylcyclopentenol and dissolve it in 10g of diethyl ether. Add the diethyl ether solution of tetramethylcyclopentenol and n-pentane sequentially through the feed port. Maintain negative pressure at the discharge port to collect the solution. Stop collecting after confirming that there is no product by GC-MS detection. The negative pressure at the discharge port is 40kPa.

[0061] (4) The solution collected in step (3) was concentrated to obtain 10.2 g (83.6 mmol) of pale yellow liquid, with a yield of 83.6%.

[0062] The product was characterized by NMR and GC-MS, and the results are as follows:

[0063] 1 H NMR (400MHz, CDCl3): δ (ppm) = 2.77 (s, 2H), 1.96 (s, 6H), 1.85 (s, 6H).

[0064] The purity of the product was determined to be 99.9% by GC-MS.

[0065] Example 2

[0066] This embodiment provides a method for synthesizing pentamethylcyclopentadiene, as detailed below:

[0067] (1) Weigh 861 mg (5 mmol) of p-toluenesulfonic acid, 86.1 mg of 2,6-di-tert-butyl-p-cresol, 86.1 g of silica gel, and 43 g of diethyl ether, mix them evenly, and evaporate the solvent to obtain loaded silica gel.

[0068] (2) The loaded silica gel and molecular sieve prepared in step (1) are loaded into a packing column to form a loaded silica gel layer and a molecular sieve layer in the packing column. The thickness ratio of the loaded silica gel layer to the molecular sieve layer is 1:2. The filled packing column is placed horizontally, with one end of the packing column near the loaded silica gel layer as the inlet and the other end as the outlet.

[0069] (3) Weigh 15.4g (100mmol) of pentamethylcyclopentenol and dissolve it in 10g of diethyl ether. Add the pentamethylcyclopentenol diethyl ether solution and n-pentane sequentially through the inlet. Maintain negative pressure at the outlet to collect the solution. Stop collecting after confirming that there is no product by GC-MS detection. The negative pressure at the outlet is 40kPa.

[0070] (4) The solution collected in step (3) was concentrated to obtain 11.6 g (85.2 mmol) of pale yellow liquid, with a yield of 85.2%.

[0071] The product was characterized by NMR and GC-MS, and the results are as follows:

[0072] 1 H NMR (400MHz, CDCl3): δ (ppm) = 3.01 (t, 1H), 2.21 (s, 6H), 1.79 (s, 6H), 0.46 (d, 2H).

[0073] The purity of the product was determined by GC-MS to be 98.8%.

[0074] Comparative Example 1

[0075] This comparative example involves the synthesis of tetramethylcyclopentadiene, and differs from Example 1 in that the polymerization inhibitor 2,6-di-tert-butyl-p-cresol was not added in step (1). The specific operation is as follows:

[0076] (1) Weigh 861 mg (5 mmol) of p-toluenesulfonic acid, 86.1 g of silica gel and 43 g of diethyl ether, mix them evenly, and evaporate the solvent to obtain loaded silica gel.

[0077] (2) The loaded silica gel and molecular sieve prepared in step (1) are loaded into a packing column to form a loaded silica gel layer and a molecular sieve layer in the packing column. The thickness ratio of the loaded silica gel layer to the molecular sieve layer is 1:2. The filled packing column is placed horizontally, with one end of the packing column near the loaded silica gel layer as the inlet and the other end as the outlet.

[0078] (3) Weigh out 14.2 g of tetramethylcyclopentenol (100 mmol) and dissolve it in 10 g of diethyl ether. Add the diethyl ether solution of tetramethylcyclopentenol and n-pentane sequentially through the feed port. Maintain negative pressure at the discharge port to collect the solution. Stop collecting after confirming that there is no product by GC-MS detection. The negative pressure at the discharge port is 40 kPa.

[0079] (4) The solution collected in step (3) is concentrated to obtain a pale yellow, slightly viscous liquid.

[0080] The product was characterized by GC-MS, and the results showed that the purity of the product was about 88%, and the main impurities were dimers and polymers of the product.

[0081] Comparative Example 2

[0082] This comparative example involves the synthesis of tetramethylcyclopentadiene using a one-pot method, the specific steps of which are as follows:

[0083] Weigh 14.2 g (100 mmol) of tetramethylcyclopentenol, 861 mg (5 mmol) of p-toluenesulfonic acid, 86.1 mg of 2,6-di-tert-butyl-p-cresol, and 53 g of diethyl ether into a reaction flask, stir at room temperature for 0.5 h, quench the reaction with water, extract with diethyl ether, combine the organic phases, concentrate to remove the solvent, and obtain a pale yellow, slightly viscous liquid.

[0084] The product was characterized by GC-MS, and the results showed that the purity of the product was 74%, and the main impurities were dimers and polymers of the current product.

[0085] Comparative Example 3

[0086] This comparative example involves the synthesis of tetramethylcyclopentadiene. The difference from Comparative Example 2 is that the reaction time is extended. The specific operation is as follows:

[0087] Weigh 14.2 g (100 mmol) of tetramethylcyclopentenol, 861 mg (5 mmol) of p-toluenesulfonic acid, 86.1 mg of 2,6-di-tert-butyl-p-cresol, and 53 g of diethyl ether into a reaction flask, stir at room temperature for 2 h, quench the reaction with water, extract with diethyl ether, combine the organic phases, concentrate to remove the solvent, and obtain a deep yellow viscous liquid.

[0088] The product was characterized by GC-MS. The results showed that the main components of the product were dimers and polymers of tetramethylcyclopentadiene, and no peak of the target product was found.

[0089] The embodiments described above are merely preferred examples to fully illustrate the present invention, and the scope of protection of the present invention is not limited thereto. Equivalent substitutions or modifications made by those skilled in the art based on the present invention are all within the scope of protection of the present invention. The scope of protection of the present invention is defined by the claims.

Claims

1. A method for preparing a cyclopentadiene derivative, characterized in that, Includes the following steps: (1) Mix silica gel with polymerization inhibitor, dehydration catalyst and solvent evenly, and dry to obtain loaded silica gel; (2) The loaded silica gel and molecular sieve are added to the packing column in sequence to form a loaded silica gel layer and a molecular sieve layer in the packing column; and the filled packing column is placed horizontally, with one end of the packing column near the loaded silica gel layer as the feed port and the other end as the discharge port. (3) Dissolve the cyclopentadienol derivative shown in formula (I) in an ether solvent to obtain a cyclopentadienol derivative solution. Then add the cyclopentadienol derivative solution and the alkane solvent one after the other into the feed port of the packing column, and maintain the negative pressure at the discharge port to collect the mixed solution flowing out of the discharge port. (4) The mixed solution collected in step (3) is concentrated and the solvent is removed to obtain the cyclopentadiene derivative shown in formula (II); The structures of equations (I) and (II) above are shown below: 、 ， R1, R2, R3, R4, and R5 are each independently selected from H and C1 to C20 alkyl groups; The silica gel is 300-400 mesh chromatography silica gel; The polymerization inhibitor is selected from one or more of 2,6-di-tert-butyl-p-cresol, p-cresol, and hydroquinone; The dehydration catalyst is selected from one or more of p-toluenesulfonic acid, p-nitrobenzenesulfonic acid, benzenesulfonic acid, and hydrochloric acid; The solvent is selected from one or more of diethyl ether, n-pentane, n-hexane, methyl tert-butyl ether, and isopropyl ether; The mass ratio of the silica gel to the polymerization inhibitor and the dehydration catalyst is 100:0.05-0.2:0.5-2.

2. The preparation method according to claim 1, characterized in that, In step (2), the thickness ratio of the loaded silica layer to the molecular sieve layer is 1:1-10.

3. The preparation method according to claim 1, characterized in that, In step (2), the packing column is made of glass, 316 stainless steel or polypropylene.

4. The preparation method according to claim 1, characterized in that, In step (3), the ether solvent is one or more of diethyl ether, methyl tert-butyl ether, and isopropyl ether.

5. The preparation method according to claim 1, characterized in that, In step (3), the molar ratio of the cyclopentadienol derivative to the dehydration catalyst in the cyclopentadienol derivative solution is 20-100:

1.

6. The preparation method according to claim 1, characterized in that, In step (3), the alkane solvent is selected from one or more of n-pentane, n-hexane, and n-heptane.

7. The preparation method according to claim 1, characterized in that, In step (4), the pressure of the negative pressure is 10-80 kPa.

8. The preparation method according to claim 1, characterized in that, R1-R4 are methyl groups, and R5 is H or methyl.

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