A process for the synthesis of cis-1,4-cyclohexanediol

Abstract

The application belongs to the technical field of organic chemical synthesis, and particularly relates to a synthesis method of cis-1,4-cyclohexanediol. The method takes 1,4-cyclohexanedione as a raw material, and uses a large steric ruthenium catalyst to control the reaction selectivity, so as to synthesize cis-1,4-cyclohexanediol in one step. The method has the advantages of high yield, few reaction steps, high cis / trans selectivity, green environmental protection and the like.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic chemical synthesis, and particularly relates to a synthesis method of cis-1,4-cyclohexanediol. BACKGROUND

[0002] 1,4-cyclohexanediol contains two hydroxyl groups and has a ring structure, and is relatively active in chemical properties, and has certain rigidity, and is widely applied to the industries of medicine, material, pesticide and the like. 1,4-cyclohexanediol is divided into cis-1,4-cyclohexanediol and trans-1,4-cyclohexanediol, as shown below, and cis-1,4-cyclohexanediol and trans-1,4-cyclohexanediol are different compounds, and have different spatial structures and different physical and chemical properties in many aspects.

[0003]

[0004] Cis-1,4-cyclohexanediol has very important value and unique performance in chiral reagents and polymers, and the synthesis method of cis-1,4-cyclohexanediol is also more and more concerned.

[0005] The synthesis methods of cis-1,4-cyclohexanediol mainly include the following methods:

[0006] (1) In Chemistry-A European Journal, 2009, 15 (28), 6953-6963, the author uses hydroquinone as a raw material, uses Ru / C as a catalyst, and prepares a 1,4-cyclohexanediol mixture under the atmosphere of 10 atmospheres of hydrogen for 24 hours at 90 degrees. The cis-trans ratio of the product is 75:25. Although the synthesis route of this method is simple, it cannot effectively prepare 1,4-cyclohexanediol with a high cis-trans ratio.

[0007]

[0008] (2) In Bioorganic & Medicinal Chemistry Letters, 2015, 25 (3), 695-700, the author starts from a raw material of glycol protected carbonyl, removes the protecting group in hydrochloric acid aqueous solution, and prepares a 1,4-cyclohexanediol mixture. The biggest disadvantage of this method is that the raw material is not easy to obtain.

[0009]

[0010] (3) In Chemistry Express, 1993, 8(7), 495-498, the author synthesized 1,4-cyclohexanediol mixture with 50:50 cis:trans ratio using 2,3,4,5-tetrabromohydroquinone as raw material under the catalysis of Ni-Al alloy, and cis-1,4-cyclohexanediol was not synthesized.

[0011]

[0012] (4) In patent CN 107759446 A, the author synthesized cis-1,4-cyclohexanediol by hydrolysis after separating the cis intermediate product by column chromatography after reducing 4-(hydrocarbyl acyloxy) cyclohexanone as raw material. The method is complicated, only 50% of the intermediate is used, the atomic economy is low, and the separation by column chromatography is not suitable for large-scale preparation.

[0013]

[0014] (5) In Tetrahedron Letters, 2014, 55, 128-132, the author synthesized 1,4-cyclohexanediol by hydrogenation under the action of ruthenium catalyst, but unfortunately the mixture obtained could not obtain single configuration product.

[0015]

[0016] Based on the above-mentioned methods, the main shortcomings are: complicated steps, long reaction time, high cost, difficult to obtain raw materials, and difficult to separate the mixture. SUMMARY

[0017] In view of the technical problems existing in the prior art, the purpose of the present application is to provide a synthesis method of cis-1,4-cyclohexanediol which has fewer reaction steps, easy to obtain raw materials, high product purity and is suitable for mass production.

[0018] To achieve the above-mentioned purpose, the technical scheme adopted by the present application is as follows:

[0019] The synthesis method of cis-1,4-cyclohexanediol has the following synthesis route:

[0020]

[0021] The synthesis steps are: adding 1,4-cyclohexanediol, catalyst, hydrogen source, base and solvent in a reactor, stirring at 30-100℃ for 5-48h, cooling to room temperature after the reaction is completed, quenching the reaction with saturated sodium bicarbonate aqueous solution, extracting the organic phase in the system with organic solvent, and then concentrating, purifying and treating to obtain cis-1,4-cyclohexanediol.

[0022] Preferably, the catalyst is a large steric hindrance ruthenium-based catalyst, and its structural formula is one of the following formulas L1-L12:

[0023]

[0024] Preferably, the molar ratio of the 1,4-cyclohexanedione to the catalyst is 800-10000:1.

[0025] Preferably, the hydrogen source is formic acid, ammonium formate, acetic acid, ethanol or ammonia.

[0026] Preferably, the molar ratio of the 1,4-cyclohexanedione to the hydrogen source is 1:5-20.

[0027] Preferably, the base is sodium hydroxide, potassium hydroxide, cesium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, trimethylamine, dimethylamine, triethylamine, diethylamine, tricyclohexylamine, dicyclohexylamine, sodium methoxide, potassium ethoxide, sodium tert-butoxide, butyllithium, tert-butyllithium or diisopropylaminyl lithium.

[0028] Preferably, the molar ratio of the 1,4-cyclohexanedione to the base is 1:5-50.

[0029] Preferably, the solvent is N-methylpyrrolidone, 2-methyltetrahydrofuran, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dichloromethane, toluene, xylene, methanol, ethanol, dichloroethane, chloroform, acetonitrile, dimethyl sulfoxide or hexamethylphosphoramide.

[0030] Preferably, the concentration of the 1,4-cyclohexanedione in the solvent is 0.1-5 mol / L (abbreviated as M).

[0031] Preferably, the organic solvent is ethyl acetate, methyl tert-butyl ether, dichloromethane, diethyl ether or trichloromethane.

[0032] Beneficial effects: the present application uses a large steric hindrance ruthenium-based catalyst to control the reaction selectivity, and a high cis / trans ratio one-step synthesis of cis-1,4-cyclohexanediol, which has the advantages of high yield, few reaction steps, high cis / trans selectivity, green environmental protection and the like. BRIEF DESCRIPTION OF DRAWINGS

[0033] Figure 1 It is the nuclear magnetic resonance hydrogen spectrum of the target product cis-1,4-cyclohexanediol obtained in Example 1 of the present application.

[0034] Figure 2 It is the nuclear magnetic resonance carbon spectrum of the target product cis-1,4-cyclohexanediol obtained in Example 1 of the present application. DETAILED DESCRIPTION

[0035] The application will be described in detail below with reference to examples, but the scope of the application is not limited to the following examples.

[0036] Example 1

[0037] A synthesis method of cis-1,4-cyclohexanediol: in a reactor, 1,4-cyclohexanedione (molar equivalent 1), catalyst L1 (molar equivalent 0.001), formic acid as hydrogen source (molar equivalent 10), sodium tert-butoxide as base (molar equivalent 20), dichloromethane as solvent (0.2M), stirring at 30°C for 10h, after the reaction is completed, cooling to room temperature, quenching the reaction with saturated aqueous sodium bicarbonate solution, extracting the organic phase in the system with ethyl acetate, filtering with diatomite, concentrating the organic phase, removing the solvent to obtain cis-1,4-cyclohexanediol, with a yield of 95%.

[0038] The target product is subjected to nuclear magnetic characterization, and the results are as follows:

[0039] 1 HNMR (400MHz, [D6]DMSO): δ 4.29 (s, 2H), 3.51 (m, 2H), 1.59-1.36 (m, 8H);

[0040] 13 CNMR (400MHz, [D6]DMSO): δ 65.89, 30.37.

[0041] The melting point of the target product is 98-100°C, and the density is 1.156 g / cm 3 .

[0042] Example 2

[0043] A synthesis method of cis-1,4-cyclohexanediol: in a reactor, 1,4-cyclohexanedione (molar equivalent 1), catalyst L2 (molar equivalent 0.08), ammonium formate as hydrogen source (molar equivalent 5), triethylamine as base (molar equivalent 5), 1,4-dioxane as solvent (1M), stirring at 40°C for 5h, after the reaction is completed, cooling to room temperature, quenching the reaction with saturated aqueous sodium bicarbonate solution, extracting the organic phase in the system with methyl tert-butyl ether, filtering with diatomite, concentrating the organic phase, removing the solvent to obtain cis-1,4-cyclohexanediol, with a yield of 90%.

[0044] The nuclear magnetic data, melting point and density of the target product of this example are the same as those of Example 1.

[0045] Example 3

[0046] A method for synthesizing cis-1,4-cyclohexanediol: in a reactor, 1,4-cyclohexanone (molar equivalent 1), catalyst L6 (molar equivalent 0.002), acetic acid as hydrogen source (molar equivalent 20), sodium hydroxide as base (molar equivalent 15), xylene as solvent (2M), stirring at 50°C for 20h, after the reaction is completed, cooling to room temperature, quenching the reaction with saturated aqueous sodium bicarbonate solution, extracting the organic phase in the system with dichloromethane, filtering with diatomite, concentrating the organic phase, removing the solvent to obtain cis-1,4-cyclohexanediol, with a yield of 91%.

[0047] The nuclear magnetic data, melting point and density of the target product of the example are the same as those of Example 1.

[0048] Example 4

[0049] A method for synthesizing cis-1,4-cyclohexanediol: in a reactor, 1,4-cyclohexanone (molar equivalent 1), catalyst L8 (molar equivalent 0.0001), ammonia as hydrogen source (molar equivalent 15), butyllithium as base (molar equivalent 30), tetrahydrofuran as solvent (5M), stirring at 60°C for 24h, after the reaction is completed, cooling to room temperature, quenching the reaction with saturated aqueous sodium bicarbonate solution, extracting the organic phase in the system with ethyl acetate, filtering with diatomite, concentrating the organic phase, removing the solvent to obtain cis-1,4-cyclohexanediol, with a yield of 89%.

[0050] The nuclear magnetic data, melting point and density of the target product of the example are the same as those of Example 1.

[0051] Example 5

[0052] A method for synthesizing cis-1,4-cyclohexanediol: in a reactor, 1,4-cyclohexanone (molar equivalent 1), catalyst L10 (molar equivalent 0.005), ethanol as hydrogen source (molar equivalent 7), sodium bicarbonate as base (molar equivalent 40), toluene as solvent (0.5M), stirring at 80°C for 36h, after the reaction is completed, cooling to room temperature, quenching the reaction with saturated aqueous sodium bicarbonate solution, extracting the organic phase in the system with diethyl ether, filtering with diatomite, concentrating the organic phase, removing the solvent to obtain cis-1,4-cyclohexanediol, with a yield of 98%.

[0053] The nuclear magnetic data, melting point and density of the target product of the example are the same as those of Example 1.

[0054] Example 6

[0055] A method for synthesizing cis-1,4-cyclohexanediol: in a reactor, 1,4-cyclohexanedione (molar equivalent 1), catalyst L12 (molar equivalent 0.007), formic acid as hydrogen source (molar equivalent 9), potassium ethoxide as base (molar equivalent 50), N,N-dimethylformamide as solvent (0.1 M), stirring at 100°C for 48 h, after the reaction is completed, cooling to room temperature, quenching the reaction with saturated aqueous sodium bicarbonate solution, extracting the organic phase in the system with chloroform, filtering with diatomite, concentrating the organic phase, removing the solvent to obtain cis-1,4-cyclohexanediol, with a yield of 94%.

[0056] The nuclear magnetic data, melting point and density of the target product of this example are the same as those of Example 1.

Claims

1. A method for synthesizing cis-1,4-cyclohexanediol, characterized in that: In a reactor, 1,4-cyclohexanedione, catalyst, hydrogen source, base and solvent are added and stirred at 30-100°C for 5-48 hours. After the reaction is completed, the mixture is cooled to room temperature, the reaction is quenched with saturated sodium bicarbonate aqueous solution, the organic phase in the system is extracted with organic solvent, and then concentrated and purified to obtain cis-1,4-cyclohexanediol. The catalyst is a sterically hindered ruthenium catalyst, and its structural formula is one of formulas L1 to L12: The molar ratio of 1,4-cyclohexanedione to the catalyst is 800 to 10000:1; The hydrogen source is formic acid, ammonium formate, acetic acid, ethanol or ammonia, and the molar ratio of 1,4-cyclohexanedione to the hydrogen source is 1:5 to 20. The alkali is sodium hydroxide, potassium hydroxide, cesium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, trimethylamine, dimethylamine, triethylamine, diethylamine, tricyclohexylamine, dicyclohexylamine, sodium methoxide, potassium ethoxide, sodium tert-butoxide, butyllithium, tert-butyllithium, or diisopropylaminolithium, and the molar ratio of 1,4-cyclohexanedione to the alkali is 1:5 to 50.

2. The method for synthesizing cis-1,4-cyclohexanediol according to claim 1, characterized in that: The solvent is N-methylpyrrolidone, 2-methyltetrahydrofuran, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dichloromethane, toluene, xylene, methanol, ethanol, dichloroethane, chloroform, acetonitrile, dimethyl sulfoxide, or hexamethylphosphoramide.

3. The method for synthesizing cis-1,4-cyclohexanediol according to claim 1 or 2, characterized in that: The concentration of the 1,4-cyclohexanedione in the solvent is 0.1–5 mol / L.

4. The method for synthesizing cis-1,4-cyclohexanediol according to claim 1, characterized in that: The organic solvent is ethyl acetate, methyl tert-butyl ether, dichloromethane, diethyl ether, or chloroform.

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