A method for synthesizing trans, trans-4-alkylbiscyclohexylcarboxylic acid

Abstract

The present application relates to the technical field of chemical synthesis, and specifically discloses a synthetic method of trans, trans-4-alkyl biscyclohexyl carboxylic acid. The synthetic method of trans, trans-4-alkyl biscyclohexyl carboxylic acid disclosed in the present application, including sequentially performing the following steps: adding raw material 4-alkylcyclohexyl benzoic acid, catalyst palladium carbon and co-catalyst chloronorbornadiene rhodium dimer to a solvent, carrying out hydrogenation reaction under the conditions of a temperature of 10-60 DEG C and a pressure of 1-10atm, and obtaining the trans, trans-4-alkyl biscyclohexyl carboxylic acid through post-treatment after the reaction. The method directly obtains trans, trans-4-alkyl biscyclohexyl carboxylic acid product by a one-step method, and the process is simple, can avoid the large-scale production of cis impurities, and reduces subsequent transformation steps; and the amount of three wastes generated during the preparation process is small, the obtained product is easy to purify and the yield is high, and the catalyst system can be repeatedly applied, reducing production costs.

Description

Technical Field

[0001] The present application relates to the technical field of chemical synthesis, and in particular to a method for synthesizing trans, trans-4-alkyldicyclohexylcarboxylic acid. Background Art

[0002] Rhodium metal complexes, as catalysts, offer high activity and selectivity, safe and mild reaction conditions, and have made significant progress in research, particularly in polymerization, formylation, and carbonylation reactions. Rhodium metal catalysts have also been reported in catalytic hydrogenation. However, rhodium reagents are expensive and rarely used in industry.

[0003] Trans, trans-4-alkylbiscyclohexylcarboxylic acid (nCCA) is a commonly used organic intermediate, mostly used in the synthesis of fine chemicals such as organic liquid crystals, such as the synthesis of carboxylic acid derivatives or alcohol liquid crystal intermediates, or directly used in the synthesis of ester liquid crystal monomers. It has a large market demand.

[0004] nCCA products are generally synthesized by hydrogenating 4-alkylcyclohexylbenzoic acid (nPCA) raw materials under alkaline conditions, which requires converting the benzene ring in the structure into a cyclohexyl ring group. This reaction is characterized by harsh hydrogenation conditions, requiring a large amount of catalyst, and requiring high temperature and high pressure conditions. Moreover, the nCCA product produced by this hydrogenation route has a high cis-isomer content, often exceeding 50%, and requires a transformation reaction to convert it into the desired trans product. The reaction equation is shown in Equation (2).

[0005] Formula (2).

[0006] In recent years, in response to safety production and environmental protection policies, and to cope with an increasingly stringent market environment, the production process for these products has urgently needed improvement. Conventional nCCA production processes require high temperatures and high pressures, which are inconsistent with safety production principles. Furthermore, the acids and bases used in the cis-transformation process are not only hazardous chemicals, but also pose significant environmental risks. Summary of the Invention

[0007] In order to solve the above technical problems, the present application provides a method for synthesizing trans, trans-4-alkylbiscyclohexylcarboxylic acid.

[0008] The present application provides a method for synthesizing trans, trans-4-alkylbiscyclohexylcarboxylic acid, which specifically comprises the following steps in sequence:

[0009] In a solvent, a raw material 4-alkylcyclohexylbenzoic acid, a catalyst palladium carbon and a co-catalyst chlorobornadiene rhodium dimer are sequentially added, and a hydrogenation reaction is carried out at a temperature of 10-60° C. and a pressure of 1-10 atm. After the reaction is completed, post-treatment is performed to obtain the trans,trans-4-alkylbiscyclohexylcarboxylic acid;

[0010] The weight ratio of the palladium carbon to the raw material is 0.005-0.05:1; the molar ratio of the chlorobornadiene rhodium dimer to the raw material is 0.0025-0.05:1;

[0011] The reaction formula is shown in formula (1), wherein n is any one of the C1-C5 straight-chain alkanes;

[0012]

[0013] Formula (1).

[0014] The method for synthesizing trans,trans-4-alkylbiscyclohexylcarboxylic acid disclosed in the present application comprises a step of hydrogenating 4-alkylcyclohexylbenzoic acid as a raw material in the presence of a palladium-carbon catalyst and a co-catalyst metal rhodium ligand reagent, chlorobornadiene rhodium dimer, to directly obtain the trans,trans-4-alkylbiscyclohexylcarboxylic acid (nCCA) product. The method is simple to prepare, avoids the generation of large amounts of cis-form impurities, and reduces the number of subsequent transformation steps. The preparation process also generates low amounts of three wastes, and the obtained product is easy to purify with a high yield. The catalyst system can be repeatedly used, thereby reducing production costs.

[0015] Preferably, the 4-alkylcyclohexylbenzoic acid is selected from any one of 4-methylcyclohexylbenzoic acid, 4-ethylcyclohexylbenzoic acid, 4-propylcyclohexylbenzoic acid, 4-butylcyclohexylbenzoic acid, and 4-pentylcyclohexylbenzoic acid.

[0016] Preferably, the catalyst is palladium carbon, with a palladium content of 5%-10% and a water content of 40%-60%.

[0017] Preferably, the weight ratio of the palladium carbon to the raw material is 0.01-0.02:1.

[0018] In a specific embodiment, the weight ratio of palladium carbon to raw material can be 0.005:1, 0.01:1, 0.02:1, 0.03:1, 0.04:1, 0.05:1

[0019] Through experimental analysis, it can be seen that the present application selects to control the weight ratio of palladium carbon to raw materials within the above range, which can further improve the reaction efficiency and yield of the synthesis method of trans, trans-4-alkylbiscyclohexylcarboxylic acid.

[0020] Preferably, the molar ratio of the chlorobornadiene rhodium dimer to the raw material is 0.005-0.015:1.

[0021] In a specific embodiment, the molar ratio of the chlorobornadiene rhodium dimer to the raw material can be 0.00255:1, 0.005:1, 0.01:1, 0.015:1, 0.02:1, 0.025:1, 0.03:1, 0.035:1, 0.04:1, 0.045:1, or 0.05:1.

[0022] Through experimental analysis, it can be seen that the present application selects to control the molar ratio of chlorobornadiene rhodium dimer to the raw material within the above range, which can further improve the reaction efficiency and yield of the synthesis method of trans, trans-4-alkylbiscyclohexylcarboxylic acid.

[0023] Preferably, the solvent is selected from one or more of methanol, ethanol, isopropanol, tetrahydrofuran, and 2-methyltetrahydrofuran.

[0024] Preferably, the solvent is composed of a mixture of isopropyl alcohol and 2-methyltetrahydrofuran in a weight ratio of 10:0.5-1.5.

[0025] In a specific embodiment, in the solvent composition, the weight ratio of the isopropyl alcohol to the 2-methyltetrahydrofuran can be 10:0.5, 10:1, or 10:1.5.

[0026] Through experimental analysis, it can be known that the present application selects the above-mentioned ratio of isopropyl alcohol and 2-methyltetrahydrofuran mixed to form a solvent, which can further improve the reaction efficiency and yield of the synthesis method of trans, trans-4-alkylbiscyclohexylcarboxylic acid.

[0027] Preferably, the solvent is selected from one or more of methanol, ethanol, isopropanol, tetrahydrofuran, and 2-methyltetrahydrofuran; and the amount of the solvent used is 2-5 times the weight of the raw material.

[0028] Preferably, the reaction temperature is 20-40° C., the pressure is 2-4 atm, and the reaction time is 1-10 h.

[0029] In a specific embodiment, the reaction temperature can be 10°C, 20°C, 30°C, 40°C, 50°C, or 60°C.

[0030] In a specific embodiment, the pressure can be 1 atm, 2 atm, 3 atm, 4 atm, 5 atm, or 10 atm.

[0031] Preferably, the post-processing comprises performing the following steps in sequence:

[0032] The catalyst is recovered by filtration; the filtrate is subjected to desolventization and recrystallization to obtain a qualified product; the recovered catalyst system is applied according to the above operation;

[0033] The purification solvent for the recrystallization is selected from any one of toluene, petroleum ether and n-heptane.

[0034] In summary, the technical solution of this application has the following effects:

[0035] The present invention improves the catalytic system and directly synthesizes di-trans nCCA-type organic intermediates by hydrogenating nPCA. The advantages are: avoiding transformation reactions and shortening the process; avoiding the large-scale use of acids and bases, which is more in line with environmental protection concepts; the hydrogenation temperature and pressure used are lower than those of conventional processes, greatly reducing energy consumption, and can adapt to safety and environmental protection requirements. The catalyst usage is small and can be reused repeatedly, reducing preparation costs. DETAILED DESCRIPTION

[0036] The present application is further described in detail below in conjunction with examples, comparative examples and performance testing experiments. These examples should not be construed as limiting the scope of protection claimed in this application. Example Example 1

[0037] Example 1 provides a method for synthesizing trans, trans-4-alkylbiscyclohexylcarboxylic acid.

[0038] The specific steps of the synthesis method of trans, trans-4-alkylbiscyclohexylcarboxylic acid in this embodiment are as follows.

[0039] To a 2L autoclave, 738.9g of solvent (a mixture of isopropanol and 2-methyltetrahydrofuran in a 10:1 weight ratio, three times the weight of the starting material) was added, followed by 1 mol of the starting material, 246.3g of 4-propylcyclohexylbenzoic acid (3PCA), 2.5g of palladium-on-carbon catalyst (0.01:1 weight ratio to the starting material), and 2.3g of [Rh(nbd)Cl]2-chloronorbornadiene rhodium dimer (0.005:1 molar ratio to the starting material). After nitrogen and hydrogen displacement, hydrogenation was carried out at 30°C and 3 atm until complete conversion of the starting material. After completion of the reaction, the catalyst was recovered by filtration, and the filtrate was desolvated and recrystallized from toluene to obtain trans,trans-4-propylbiscyclohexylcarboxylic acid (3CCA). Table 1 shows the purity spectral analysis results of the trans,trans-4-alkylbiscyclohexylcarboxylic acids in this example.

[0040] Table 1 Purity spectrum analysis results of trans, trans-4-alkylbiscyclohexylcarboxylic acid in Example 1

[0041]

[0042] Examples 2-7

[0043] Examples 2-7 respectively provide a method for synthesizing trans and trans-4-alkylbiscyclohexylcarboxylic acid.

[0044] The difference between the above embodiment and embodiment 1 is that the amount of catalyst palladium carbon or co-catalyst used is different, as shown below.

[0045] In Example 2, the amount of the catalyst palladium-carbon used was 1.25 g, and the weight ratio to the raw material was 0.005:1.

[0046] In Example 3, the amount of the catalyst palladium carbon used was 5 g, and the weight ratio to the raw material was 0.02:1.

[0047] In Example 4, the amount of the catalyst palladium carbon used was 12.5 g, and the weight ratio to the raw material was 0.05:1.

[0048] In Example 5, the amount of the co-catalyst [Rh(nbd)Cl]2 used was 1.15 g, and the molar ratio to the raw material was 0.0025:1.

[0049] In Example 6, the amount of the co-catalyst [Rh(nbd)Cl]2 used was 6.9 g, and the molar ratio to the raw material was 0.015:1.

[0050] In Example 7, the amount of the co-catalyst [Rh(nbd)Cl]2 used was 23 g, and the molar ratio to the raw material was 0.05:1.

[0051] The other process parameters in the above embodiment are the same as those in Example 1.

[0052] Examples 8-13

[0053] Examples 8-13 respectively provide a method for synthesizing trans and trans-4-alkylbiscyclohexylcarboxylic acid.

[0054] The difference between the above embodiment and embodiment 1 is that the types of solvents are different, as shown below.

[0055] In Example 8: the solvent is isopropyl alcohol.

[0056] In Example 9, the solvent is a mixture of ethanol and 2-methyltetrahydrofuran in a weight ratio of 10:1.

[0057] In Example 10, the solvent is a mixture of isopropyl alcohol and tetrahydrofuran in a weight ratio of 10:1.

[0058] In Example 11, the solvent is a mixture of isopropyl alcohol and 2-methyltetrahydrofuran in a weight ratio of 1:10.

[0059] In Example 12, the solvent is a mixture of isopropyl alcohol and 2-methyltetrahydrofuran in a weight ratio of 10:0.5.

[0060] In Example 13, the solvent is a mixture of isopropyl alcohol and 2-methyltetrahydrofuran in a weight ratio of 10:1.5.

[0061] The other process parameters in the above embodiment are the same as those in Example 1.

[0062] Examples 14-17

[0063] Examples 14-17 respectively provide a method for synthesizing trans and trans-4-alkylbiscyclohexylcarboxylic acid.

[0064] The difference between the above embodiment and embodiment 1 is that the types of solvents are different, as shown below.

[0065] In Example 14: the reaction temperature was 10°C.

[0066] In Example 15: the reaction temperature was 20°C.

[0067] In Example 16: the reaction temperature is 40°C.

[0068] In Example 17: the reaction temperature is 60°C.

[0069] The other process parameters in the above embodiment are the same as those in Example 1. Example 18

[0070] Example 18 provides a method for synthesizing trans,trans-4-alkylbiscyclohexylcarboxylic acid.

[0071] The specific steps of the synthesis method of trans, trans-4-alkylbiscyclohexylcarboxylic acid in this embodiment are as follows.

[0072] To a 2L autoclave was added 738.9 g of solvent (composed of a mixture of isopropanol and 2-methyltetrahydrofuran in a weight ratio of 10:1, the amount being 3 times the weight of the raw materials), followed by the addition of 1 mol of the raw material 4-propylcyclohexylbenzoic acid (246.3 g) (3PCA) and the catalyst recovered in Example 1. After nitrogen and hydrogen were replaced, a hydrogenation reaction was carried out at a temperature of 30°C and a pressure of 3 atm until the raw material was completely converted. After the reaction was completed, the catalyst was recovered by filtration, and the filtrate was desolvated and recrystallized from toluene to obtain trans,trans-4-alkylbiscyclohexylcarboxylic acid. Comparative Example

[0073] Comparative Examples 1-7

[0074] Comparative Examples 1-7 respectively provide a method for synthesizing trans and trans-4-alkylbiscyclohexylcarboxylic acid.

[0075] The differences between the comparative example and Example 1 are specifically as follows.

[0076] In Comparative Example 1, the amount of the catalyst palladium carbon used was 0.625 g, and the weight ratio to the raw material was 0.0025:1.

[0077] In Comparative Example 2, the amount of the catalyst palladium carbon used was 17.5 g, and the weight ratio to the raw material was 0.07:1.

[0078] In Comparative Example 3, no co-catalyst chlorobornadiene rhodium dimer was added.

[0079] In Comparative Example 4, an equal amount of triphenylphosphine rhodium chloride was used to replace the chlorobornadiene rhodium dimer.

[0080] In Comparative Example 5, the amount of the co-catalyst [Rh(nbd)Cl]2 used was 0.46 g, and the molar ratio to the raw material was 0.001:1.

[0081] In Comparative Example 6, the amount of the co-catalyst [Rh(nbd)Cl]2 used was 32.2 g, and the molar ratio to the raw material was 0.07:1.

[0082] In Comparative Example 7: the reaction temperature was 70°C.

[0083] The other process parameters in the above comparative example are the same as those in Example 1.

[0084] Performance test results

[0085] Record the reaction time, purity and yield of the synthesis method of trans, trans-4-alkylbiscyclohexylcarboxylic acid in the examples and comparative examples.

[0086] Test results: as shown in Table 2.

[0087] Table 2 Performance test results of the synthesis method of trans, trans-4-alkylbiscyclohexylcarboxylic acid in Examples and Comparative Examples

[0088]

[0089] The test results in the above table indicate that the technical solution provided by this application utilizes 4-alkylcyclohexylbenzoic acid as the raw material. A hydrogenation reaction is carried out at a temperature of 10-60°C and a pressure of 1-10 atm, using the catalyst palladium-on-carbon and the co-catalyst metal rhodium ligand reagent chlorobornadiene rhodium dimer. This method directly yields trans,trans-4-alkylbiscyclohexylcarboxylic acid (nCCA) in a single step. This method is simple, eliminating the need for high temperature and high pressure reaction conditions, avoiding the production of large amounts of cis-form impurities and reducing the number of subsequent transformation steps. Furthermore, the preparation process generates minimal waste, the resulting product is easy to purify, and the yield is high. Furthermore, the catalyst system can be reused repeatedly, reducing production costs and possessing significant market potential.

[0090] By comparing the test results of Examples 1-4 and Comparative Examples 1-2, it can be seen that the amount of catalyst palladium carbon used in Comparative Example 1 is 0.625g, and the weight ratio to the raw material is 0.0025:1. The amount of catalyst palladium carbon used in Comparative Example 2 is 17.5g, and the weight ratio to the raw material is 0.07:1. The effect of the synthesis method of trans, trans-4-alkylbiscyclohexylcarboxylic acid is poor. In contrast, the present application selects to control the weight ratio of palladium carbon to raw material to 0.005-0.05:1, which effectively improves the synthesis effect and yield of trans, trans-4-alkylbiscyclohexylcarboxylic acid.

[0091] By comparing the test results of Examples 1, 5-7, and Comparative Examples 3-6, it can be seen that in Comparative Example 3, no co-catalyst was added, and in Comparative Example 4, an equal amount of triphenylphosphine rhodium chloride was used instead of chlorobornadiene rhodium dimer as a co-catalyst. The results of the method for synthesizing trans,trans-4-alkylbiscyclohexylcarboxylic acid were relatively poor. In Comparative Example 5, the amount of co-catalyst [Rh(nbd)Cl]2 used was 0.46 g, with a molar ratio to the raw material of 0.001:1; in Comparative Example 6, the amount of co-catalyst [Rh(nbd)Cl]2 used was 32.2 g, with a molar ratio to the raw material of 0.07:1. The method for synthesizing trans,trans-4-alkylbiscyclohexylcarboxylic acid was relatively poor. In contrast, the present application selects chlorobornadiene rhodium dimer as a co-catalyst and controls the molar ratio of chlorobornadiene rhodium dimer to the raw material to be 0.0025-0.05:1, which effectively improves the synthesis efficiency and yield of trans, trans-4-alkylbiscyclohexylcarboxylic acid.

[0092] By comparing the test results of Examples 1 and 8-13, it can be seen that the present application selects a solvent composed of a mixture of isopropanol and 2-methyltetrahydrofuran in a weight ratio of 10:0.5-1.5, which can further improve the synthesis efficiency and yield of trans,trans-4-alkylbiscyclohexylcarboxylic acid.

[0093] By comparing the test results of Examples 1, 14-17, and Comparative Example 7, it can be seen that the synthesis method of trans,trans-4-alkylbiscyclohexylcarboxylic acid is less effective when the reaction temperature is high. In contrast, the present application selects a reaction temperature of 10-60°C, which can effectively improve the synthesis efficiency and yield of trans,trans-4-alkylbiscyclohexylcarboxylic acid.

[0094] Although the present invention has been described in detail above using general descriptions and specific embodiments, it will be apparent to those skilled in the art that modifications and improvements may be made based on the present invention. Therefore, such modifications and improvements, which do not depart from the spirit of the present invention, are intended to be within the scope of protection claimed herein.

Claims

1. A method for synthesizing trans, trans-4-alkylbiscyclohexylcarboxylic acid, characterized in that: Specifically, the following steps are performed in sequence: The raw material 4-alkylcyclohexylbenzoic acid, the catalyst palladium carbon and the co-catalyst chlorobornadiene rhodium dimer are sequentially added to the solvent, and a hydrogenation reaction is carried out at a temperature of 10-60° C. and a pressure of 1-10 atm. After the reaction is completed, the trans,trans-4-alkylbiscyclohexylcarboxylic acid is obtained by post-treatment; The weight ratio of the palladium carbon to the raw material is 0.005-0.05:1; the molar ratio of the chlorobornadiene rhodium dimer to the raw material is 0.0025-0.05:1; The reaction formula is shown in formula (1), wherein n is any one of the C1-C5 straight-chain alkanes; Formula (1).

2. The synthetic method of trans, trans-4-alkylbiscyclohexylcarboxylic acid according to claim 1, wherein The 4-alkylcyclohexylbenzoic acid is selected from any one of 4-methylcyclohexylbenzoic acid, 4-ethylcyclohexylbenzoic acid, 4-propylcyclohexylbenzoic acid, 4-butylcyclohexylbenzoic acid, and 4-pentylcyclohexylbenzoic acid.

3. The synthetic method of trans, trans-4-alkylbiscyclohexylcarboxylic acid according to claim 1, wherein The catalyst is palladium carbon, the palladium content thereof is 5%-10%, and the water content is 40%-60%.

4. The synthetic method of trans, trans-4-alkylbiscyclohexylcarboxylic acid according to claim 1, wherein The weight ratio of the palladium carbon to the raw material is 0.01-0.02:

1.

5. The synthetic method of trans, trans-4-alkylbiscyclohexylcarboxylic acid according to claim 1, wherein The molar ratio of the chlorobornadiene rhodium dimer to the raw material is 0.005-0.015:

1.

6. The method for synthesizing trans, trans-4-alkylbiscyclohexylcarboxylic acid according to claim 1, wherein: The solvent is selected from one or more of methanol, ethanol, isopropanol, tetrahydrofuran, and 2-methyltetrahydrofuran.

7. The method for synthesizing trans, trans-4-alkylbiscyclohexylcarboxylic acid according to claim 6, wherein: The solvent is composed of a mixture of isopropyl alcohol and 2-methyltetrahydrofuran in a weight ratio of 10:0.5-1.

5.

8. The method for synthesizing trans, trans-4-alkylbiscyclohexylcarboxylic acid according to claim 1, wherein: The solvent is selected from one or more of methanol, ethanol, isopropanol, tetrahydrofuran, and 2-methyltetrahydrofuran; and the amount of the solvent is 2-5 times the weight of the raw material.

9. The method for synthesizing trans, trans-4-alkylbiscyclohexylcarboxylic acid according to claim 1, wherein: The reaction temperature is 20-40° C., the pressure is 2-4 atm, and the reaction time is 1-10 h.

10. The method for synthesizing trans, trans-4-alkylbiscyclohexylcarboxylic acid according to claim 1, wherein: The post-processing comprises the following steps: The catalyst is recovered by filtration; the filtrate is subjected to desolventization and recrystallization to obtain a qualified product; the recovered catalyst is reused; The purification solvent for the recrystallization is selected from any one of toluene, petroleum ether and n-heptane.

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