Synthesis method of trans, trans-4-alkyl dicyclohexyl formic acid

Abstract

The invention relates to the technical field of chemical synthesis, and particularly discloses a synthesis method of trans, trans-4-alkyl dicyclohexyl formic acid. The invention discloses a synthesis method of trans, trans-4-alkyl dicyclohexyl formic acid, which sequentially comprises the following steps: sequentially adding a raw material 4-alkyl cyclohexylbenzoic acid, a catalyst palladium-carbon and a cocatalyst chloro norbornadiene rhodium dimer into a solvent, and carrying out hydrogenation reaction under the conditions that the temperature is 10-60 DEG C and the pressure is 1-10 atm to obtain the trans, trans-4-alkyl dicyclohexyl formic acid. And after the reaction is finished, carrying out post-treatment to obtain the trans, trans-4-alkyl dicyclohexyl formic acid. According to the method, the trans, trans-4-alkyl dicyclohexyl formic acid product is directly obtained through a one-step method, the preparation process is simple, a large amount of cis-impurities can be avoided, and subsequent transformation steps are reduced; and the amount of three wastes generated in the preparation process is small, the obtained product is easy to purify and high in yield, and the catalyst system can be repeatedly used, so that the production cost is reduced.

Description

Technical Field

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

[0002] Rhodium metal complexes, as catalysts, have the characteristics of high activity and selectivity, and safe and mild reaction conditions. Great progress has been made in the research field, especially in the fields of polymerization reaction, formylation reaction, carbonylation reaction, etc. At the same time, there are also relevant reports on the catalytic hydrogenation of rhodium metal catalysts. However, rhodium reagents are expensive and rarely used in the industrial field.

[0003] Trans, trans-4-alkylbicyclohexanecarboxylic acid (nCCA) is a kind of commonly used organic intermediate, which is mostly used in the synthesis of fine chemicals such as organic liquid crystals. For example, it is used to synthesize carboxylic acid derivatives or alcohol liquid crystal intermediates or directly used to synthesize ester liquid crystal monomers, and the market demand is large.

[0004] nCCA products are generally synthesized by the method of hydrogenation of 4-alkylcyclohexanecarboxylic acid (nPCA) raw materials under alkaline conditions, and the benzene ring in the structure needs to be converted into a cyclohexyl ring group. The hydrogenation conditions of this reaction are relatively harsh, a large amount of catalyst is required, and high temperature and high pressure conditions are required for the reaction to proceed. Moreover, when synthesized according to this hydrogenation route, the cis isomer content of the generated nCCA product is large, often reaching more than 50%, and a transformation reaction is required to convert it into the required trans product. The reaction formula is shown in Formula (2); Formula (2).

[0005] In recent years, in order to respond to the policies of safe production and environmental protection, and at the same time to cope with the increasingly harsh market environment, the production process of this kind of product needs to be improved urgently. The conventional production process of nCCA requires high temperature and high pressure, which does not conform to the concept of safe production; the acids and alkalis used in the cis-trans transformation not only belong to dangerous chemicals, but also cause great environmental protection pressure. Summary of the Invention

[0006] In order to solve the above technical problems, the present application provides a method for synthesizing trans, trans-4-alkylbicyclohexanecarboxylic acid.

[0007] The present application provides a method for synthesizing trans, trans-4-alkylbicyclohexanecarboxylic acid, which specifically includes the following steps in sequence: In a solvent, add the raw material 4-alkylcyclohexanecarboxylic acid, the catalyst palladium-carbon and the co-catalyst rhodium(II) chloride norbornadiene dimer in sequence, and carry out a hydrogenation reaction under the conditions of a temperature of 10-60 °C and a pressure of 1-10 atm. After the reaction is completed, the trans, trans-4-alkylbicyclohexanecarboxylic acid is obtained through post-treatment; The weight ratio of the palladium-carbon to the raw material is 0.005 - 0.05:1; the molar ratio of the chloronorbornadiene rhodium dimer to the raw material is 0.0025 - 0.05:1; The reaction formula is shown as formula (1), where n is any one of straight-chain alkanes with C1 - C5;

[0008] Formula (1).

[0009] The synthesis method of trans,trans-4-alkylbicyclohexylcarboxylic acid disclosed in this application is a hydrogenation reaction of raw material 4-alkylcyclohexylbenzoic acid under the action of catalyst palladium-carbon and cocatalyst metal rhodium ligand reagent chloronorbornadiene rhodium dimer, and directly obtains trans,trans-4-alkylbicyclohexylcarboxylic acid (nCCA) product through a one-step method; this method has a simple process, can avoid generating a large amount of cis impurities, reduces subsequent transformation steps; and the amount of three wastes generated in the preparation process is small, the obtained product is easy to purify and has a high yield, and the catalyst system can be reused repeatedly, reducing the production cost.

[0010] Preferably, the 4-alkylcyclohexylbenzoic acid is selected from any one of 4-methylcyclohexylbenzoic acid, 4-ethylcyclohexylbenzoic acid, 4-propylcyclohexylbenzoic acid, 4-butylcyclohexylbenzoic acid, 4-pentylcyclohexylbenzoic acid.

[0011] Preferably, the catalyst is palladium-carbon, its palladium content is 5% - 10%, and the moisture content is 40% - 60%.

[0012] Preferably, the weight ratio of the palladium-carbon to the raw material is 0.01 - 0.02:1.

[0013] In a specific embodiment, the weight ratio of the palladium-carbon to the raw material can be 0.005:1, 0.01:1, 0.02:1, 0.03:1, 0.04:1, 0.05:1 Through experimental analysis, it can be known that by controlling the weight ratio of the palladium-carbon to the raw material within the above range in this application, the reaction efficiency and yield of the synthesis method of trans,trans-4-alkylbicyclohexylcarboxylic acid can be further improved.

[0014] Preferably, the molar ratio of the chloronorbornadiene rhodium dimer to the raw material is 0.005 - 0.015:1.

[0015] In a specific embodiment, the molar ratio of the chloronorbornadiene 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, 0.05:1.

[0016] Through experimental analysis, it is known that in this application, choosing to control the molar ratio of chloro-norbornadiene rhodium dimer to the raw materials within the above range can further improve the reaction efficiency and yield of the synthesis method of trans,trans-4-alkylbicyclohexylcarboxylic acid.

[0017] Preferably, the solvent is selected from one or more of methanol, ethanol, isopropanol, tetrahydrofuran, and 2-methyltetrahydrofuran.

[0018] Preferably, the solvent is composed of a mixture of isopropanol and 2-methyltetrahydrofuran with a weight ratio of 10:0.5-1.5.

[0019] In a specific embodiment, in the solvent composition, the weight ratio of the isopropanol to the 2-methyltetrahydrofuran can be 10:0.5, 10:1, or 10:1.5.

[0020] Through experimental analysis, it is known that in this application, choosing to use a mixture of isopropanol and 2-methyltetrahydrofuran in the above ratio as the solvent can further improve the reaction efficiency and yield of the synthesis method of trans,trans-4-alkylbicyclohexylcarboxylic acid.

[0021] Preferably, the solvent is selected from one or more of methanol, ethanol, isopropanol, tetrahydrofuran, and 2-methyltetrahydrofuran; the amount of the solvent used is 2-5 times the weight of the raw materials.

[0022] Preferably, the reaction temperature is 20-40°C, the pressure is 2-4 atm, and the reaction time is 1-10 h.

[0023] In a specific embodiment, the reaction temperature can be 10°C, 20°C, 30°C, 40°C, 50°C, or 60°C.

[0024] In a specific embodiment, the pressure can be 1 atm, 2 atm, 3 atm, 4 atm, 5 atm, or 10 atm.

[0025] Preferably, the post-treatment includes the following steps in sequence: Filter and recover the catalyst; the filtrate is subjected to desolvation and recrystallization to obtain a qualified product; the recovered catalyst system is reused according to the above operation; The purification solvent for the recrystallization is selected from any one of toluene, petroleum ether, and n-heptane.

[0026] In summary, the technical solution of this application has the following effects: By improving the catalytic system, the present invention directly synthesizes the bis-trans nCCA organic intermediate by hydrogenating nPCA, with the advantages of: avoiding the transformation reaction and shortening the process; avoiding the large use of acids and bases, which is more in line with the environmental protection concept; the hydrogenation temperature and pressure used are lower than those of the conventional process, greatly reducing the energy consumption, being able to meet the requirements of safety and environmental protection, with less catalyst consumption and the catalyst can be reused repeatedly, reducing the preparation cost. Detailed implementation manners

[0027] The following further describes the present application in detail with reference to examples, comparative examples and performance detection tests. These examples should not be construed as limiting the scope claimed in the present application. Examples Example 1

[0028] Example 1 provides a method for synthesizing trans, trans-4-alkylbicyclohexylcarboxylic acid.

[0029] The specific steps of the method for synthesizing trans, trans-4-alkylbicyclohexylcarboxylic acid in this example are as follows.

[0030] Add 738.9 g of solvent (composed of isopropanol and 2-methyltetrahydrofuran in a weight ratio of 10:1, and the dosage is 3 times the weight of the raw material) to a 2 L autoclave. Then, add 246.3 g (3PCA) of 1 mol of raw material 4-propylcyclohexanecarboxylic acid, 2.5 g of palladium-carbon catalyst (weight ratio to the raw material is 0.01:1), and 2.3 g of cocatalyst [Rh(nbd)Cl]2 dichloronorbornadiene rhodium dimer (molar ratio to the raw material is 0.005:1) in sequence. After replacing with nitrogen and hydrogen respectively, carry out the hydrogenation reaction at a temperature of 30 °C and a pressure of 3 atm until the raw material is completely converted. After the reaction ends, filter and recover the catalyst. After the filtrate is desolvated, recrystallize with toluene to obtain trans, trans-4-propylbicyclohexylcarboxylic acid (3CCA). Table 1 shows the analysis results of the purity spectrum of trans, trans-4-alkylbicyclohexylcarboxylic acid in this example.

[0031] Table 1 Analysis results of the purity spectrum of trans, trans-4-alkylbicyclohexylcarboxylic acid in Example ❶

[0032] Examples 2-7

[0033] Examples 2-7 respectively provide a method for synthesizing trans, trans-4-alkylbicyclohexylcarboxylic acid.

[0034] The differences between the above examples and Example 1 are specifically as follows: the dosages of the palladium-carbon catalyst or the cocatalyst are different, which are specifically as follows.

[0035] In Example 2: The amount of palladium-carbon catalyst used was 1.25 g, and the weight ratio to the raw materials was 0.005:1.

[0036] In Example 3: The amount of palladium-carbon catalyst used was 5 g, and the weight ratio to the raw materials was 0.02:1.

[0037] In Example 4: The amount of palladium-carbon catalyst used was 12.5 g, and the weight ratio to the raw materials was 0.05:1.

[0038] In Example 5: The amount of the cocatalyst [Rh(nbd)Cl]2 used was 1.15 g, and the molar ratio to the raw materials was 0.0025:1.

[0039] In Example 6: The amount of the cocatalyst [Rh(nbd)Cl]2 used was 6.9 g, and the molar ratio to the raw materials was 0.015:1.

[0040] In Example 7: The amount of the cocatalyst [Rh(nbd)Cl]2 used was 23 g, and the molar ratio to the raw materials was 0.05:1.

[0041] In the above examples, all other process parameters were the same as those in Example 1. Examples 8 - 13

[0042] Examples 8 - 13 respectively provided a method for synthesizing trans,trans-4-alkylbicyclohexylcarboxylic acid.

[0043] The differences between the above examples and Example 1 were specifically as follows: The types of solvents were different, as shown below.

[0044] In Example 8: The solvent was isopropanol.

[0045] In Example 9: The solvent was composed of ethanol and 2-methyltetrahydrofuran mixed at a weight ratio of 10:1.

[0046] In Example 10: The solvent was composed of isopropanol and tetrahydrofuran mixed at a weight ratio of 10:1.

[0047] In Example 11: The solvent was composed of isopropanol and 2-methyltetrahydrofuran mixed at a weight ratio of 1:10.

[0048] In Example 12: The solvent was composed of isopropanol and 2-methyltetrahydrofuran mixed at a weight ratio of 10:0.5.

[0049] In Example 13: The solvent was composed of isopropanol and 2-methyltetrahydrofuran mixed at a weight ratio of 10:1.5.

[0050] In the above examples, all other process parameters were the same as those in Example 1. Examples 14 - 17

[0051] Examples 14-17 respectively provide a method for synthesizing trans,trans-4-alkylbicyclohexylcarboxylic acid.

[0052] The differences between the above examples and Example 1 are specifically as follows: the types of solvents are different, as shown below.

[0053] In Example 14: the reaction temperature is 10 °C.

[0054] In Example 15: the reaction temperature is 20 °C.

[0055] In Example 16: the reaction temperature is 40 °C.

[0056] In Example 17: the reaction temperature is 60 °C.

[0057] Other process parameters in the above examples are the same as those in Example 1. Example 18

[0058] Example 18 provides a method for synthesizing trans,trans-4-alkylbicyclohexylcarboxylic acid.

[0059] The specific steps of the method for synthesizing trans,trans-4-alkylbicyclohexylcarboxylic acid in this example are as follows.

[0060] Add 738.9 g of solvent (composed of isopropyl alcohol and 2-methyltetrahydrofuran with a weight ratio of 10:1, and the dosage is 3 times the weight of the raw material) to a 2 L autoclave, and successively add 246.3 g (3PCA) of 1 mol of raw material 4-propylcyclohexylbenzoic acid, the catalyst recovered from Example 1. After replacing with nitrogen and hydrogen respectively, carry out a hydrogenation reaction at a temperature of 30 °C and a pressure of 3 atm until the raw material is completely converted. After the reaction is completed, filter and recover the catalyst. After the filtrate is desolvated, recrystallize with toluene to obtain trans,trans-4-alkylbicyclohexylcarboxylic acid. Comparative Example Comparative Examples 1-7

[0061] Comparative Examples 1-7 respectively provide a method for synthesizing trans,trans-4-alkylbicyclohexylcarboxylic acid.

[0062] The differences between the above comparative examples and Example 1 are specifically as follows.

[0063] In Comparative Example 1: the dosage of the catalyst palladium on carbon is 0.625 g, and the weight ratio to the raw material is 0.0025:1.

[0064] In Comparative Example 2: the dosage of the catalyst palladium on carbon is 17.5 g, and the weight ratio to the raw material is 0.07:1.

[0065] In Comparative Example 3: the cocatalyst rhodium(II) chloride norbornadiene dimer was not added.

[0066] In Comparative Example 4: Rhodium(III) chloride triphenylphosphine was used to replace rhodium(III) chloride norbornadiene dimer in an equal amount.

[0067] In Comparative Example 5: The amount of the cocatalyst [Rh(nbd)Cl]2 was 0.46 g, and the molar ratio to the raw materials was 0.001:1.

[0068] In Comparative Example 6: The amount of the cocatalyst [Rh(nbd)Cl]2 was 32.2 g, and the molar ratio to the raw materials was 0.07:1.

[0069] In Comparative Example 7: The reaction temperature was 70 °C.

[0070] Other process parameters in the above comparative examples were the same as those in Example 1. Performance test results

[0071] Record the reaction time, purity and yield of the synthesis methods of trans,trans-4-alkylbicyclohexylcarboxylic acid in the examples and comparative examples.

[0072] Test results: As shown in Table 2.

[0073] Table 2 Performance test results of the synthesis methods of trans,trans-4-alkylbicyclohexylcarboxylic acid in the examples and comparative examples

[0074]

[0075] From the test results in the above table, it can be seen that for the technical solution provided by the present application, using 4-alkylcyclohexanecarboxylic acid as the raw material, under the synergistic action of the catalyst palladium on carbon and the cocatalyst metal rhodium ligand reagent rhodium(III) chloride norbornadiene dimer, a hydrogenation reaction is carried out under the conditions of a temperature of 10-60 °C and a pressure of 1-10 atm, and the product of trans,trans-4-alkylbicyclohexylcarboxylic acid (nCCA) is directly obtained by a one-step method. This method has a simple process, does not need to carry out the reaction under high temperature and high pressure conditions, can avoid the large generation of cis impurities, reduces the subsequent transformation steps; and the amount of three wastes generated in the preparation process is small, the obtained product is easy to purify and has a high yield, and the catalyst system can be reused repeatedly, reducing the production cost, and has extremely high market prospects.

[0076] By comparing the test results of Examples 1-4 and Comparative Examples 1-2, it can be seen that in Comparative Example 1, the amount of the catalyst palladium on carbon was 0.625 g, and the weight ratio to the raw materials was 0.0025:1. In Comparative Example 2, the amount of the catalyst palladium on carbon was 17.5 g, and the weight ratio to the raw materials was 0.07:1. The effects of the synthesis methods of trans,trans-4-alkylbicyclohexylcarboxylic acid were poor. In contrast, the present application selects to control the weight ratio of palladium on carbon to the raw materials to be 0.005-0.05:1, effectively improving the synthesis effect and yield of trans,trans-4-alkylbicyclohexylcarboxylic acid.

[0077] By comparing the detection results of Examples 1, 5 - 7 and Comparative Examples 3 - 6, it can be seen that no cocatalyst was added in Comparative Example 3, and triphenylphosphine rhodium chloride was used to replace rhodium(II) chloride norbornadiene dimer as the cocatalyst in Comparative Example 4 in an equal amount, and the effect of the synthesis method of trans,trans - 4 - alkylbicyclohexylcarboxylic acid was poor. In Comparative Example 5, the amount of the cocatalyst [Rh(nbd)Cl]2 was 0.46 g, and the molar ratio to the raw materials was 0.001:1; in Comparative Example 6, the amount of the cocatalyst [Rh(nbd)Cl]2 was 32.2 g, and the molar ratio to the raw materials was 0.07:1, and the effect of the synthesis method of trans,trans - 4 - alkylbicyclohexylcarboxylic acid was poor. In contrast, the present application selects rhodium(II) chloride norbornadiene dimer as the cocatalyst and controls the molar ratio of rhodium(II) chloride norbornadiene dimer to the raw materials to be 0.0025 - 0.05:1, effectively improving the synthesis efficiency and yield of trans,trans - 4 - alkylbicyclohexylcarboxylic acid.

[0078] By comparing the detection results of Examples 1, 8 - 13, it can be seen that the present application selects a solvent composed of a mixture of isopropanol and 2 - methyltetrahydrofuran with a weight ratio of 10:0.5 - 1.5, which can further improve the synthesis efficiency and yield of trans,trans - 4 - alkylbicyclohexylcarboxylic acid.

[0079] By comparing the detection results of Examples 1, 14 - 17 and Comparative Example 7, it can be seen that when the reaction temperature is relatively high, the effect of the synthesis method of trans,trans - 4 - alkylbicyclohexylcarboxylic acid is poor. In contrast, the present application selects to control the reaction temperature to be 10 - 60 °C, which can effectively improve the synthesis efficiency and yield of trans,trans - 4 - alkylbicyclohexylcarboxylic acid.

[0080] Although the present invention has been described in detail with general descriptions and specific embodiments above, based on the present invention, some modifications or improvements can be made, which are obvious to those skilled in the art. Therefore, these modifications or improvements made without departing from the spirit of the present invention all fall within the scope of protection required by the present invention.

Claims

1. A method for synthesizing trans, trans-4-alkylbicyclohexylcarboxylic acid, characterized in that, Specifically, it includes the following steps in sequence: Add raw material 4-alkylcyclohexylbenzoic acid, catalyst palladium on carbon and cocatalyst rhodium(Ⅱ) chloride norbornadiene dimer into the solvent in sequence, and carry out the hydrogenation reaction under the conditions of a temperature of 10 - 60°C and a pressure of 1 - 10 atm. After the reaction is completed, the trans,trans-4-alkylbicyclohexylcarboxylic acid is obtained through post-treatment; The weight ratio of the palladium on carbon to the raw material is 0.005 - 0.05:1; the molar ratio of the rhodium(Ⅱ) chloride norbornadiene dimer to the raw material is 0.0025 - 0.05:1; The reaction formula is shown as formula (1), where n is any one of straight-chain alkanes with C1 - C5; Formula (1).

2. The synthesis method of trans, trans-4-alkyl bicyclohexylcarboxylic 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 synthesis method of trans, trans-4-alkylbicyclohexylcarboxylic acid according to claim 1, characterized in that, The catalyst is palladium on carbon, and its palladium content is 5% - 10%, and the water content is 40% - 60%.

4. The synthesis method of trans, trans-4-alkyl bicyclohexyl carboxylic acid according to claim 1, characterized in that, The weight ratio of the palladium on carbon to the raw material is 0.01 - 0.02:

1.

5. The synthesis method of trans, trans-4-alkyl bicyclohexylcarboxylic acid according to claim 1, characterized in that, The molar ratio of the rhodium(Ⅱ) chloride norbornadiene dimer to the raw material is 0.005 - 0.015:

1.

6. The synthesis method of trans, trans-4-alkylbicyclohexylcarboxylic acid according to claim 1, characterized in that, The solvent is selected from one or more of methanol, ethanol, isopropanol, tetrahydrofuran, and 2-methyltetrahydrofuran.

7. The synthesis method of trans, trans-4-alkyl bicyclohexylcarboxylic acid according to claim 6, characterized in that, The solvent is composed of a mixture of isopropanol and 2-methyltetrahydrofuran with a weight ratio of 10:0.5 - 1.

5.

8. The synthesis method of trans, trans-4-alkylbicyclohexylcarboxylic acid according to claim 1, characterized in that, The solvent is selected from one or more of methanol, ethanol, isopropanol, tetrahydrofuran, and 2-methyltetrahydrofuran; the dosage of the solvent is 2 - 5 times the weight of the raw material.

9. The synthesis method of trans, trans-4-alkylbicyclohexylcarboxylic 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 synthesis method of trans, trans-4-alkyl bicyclohexylcarboxylic acid according to claim 1, wherein The post-treatment includes the following steps in sequence: Filter to recover the catalyst; the filtrate is subjected to desolvation and recrystallization to obtain a qualified product; the recovered catalyst system is reused according to the above operation; The purification solvent for recrystallization is selected from any one of toluene, petroleum ether, and n-heptane.

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