Efficient catalytic hydrogenation method for difluorophenyl ether derivative
By introducing 1-adamantanol as a co-catalyst in the catalytic hydrogenation of difluorophenylethyl ether derivatives, the problems of poor stereoselectivity and low catalyst efficiency were solved, achieving a highly selective and efficient hydrogenation reaction, improving product purity and production safety, and reducing costs.
Patent Information
- Application Number
- CN202510910561.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-02
- Publication Date
- 2025-11-07
AI Technical Summary
Existing technologies for the catalytic hydrogenation of difluorophenylethyl ether derivatives suffer from poor stereoselectivity, harsh reaction conditions, low catalyst efficiency, and high cost, making it difficult to achieve highly selective and efficient hydrogenation reactions under mild conditions.
By introducing 1-adamantanol as a co-catalyst and using it in conjunction with a Pd/C catalyst, the reaction pathway is optimized through spatial orientation effect and electronic state regulation, forming a spatial confinement effect, increasing the proportion of trans isomers, and reducing catalyst dosage and reaction energy consumption.
It significantly increased the formation rate of trans isomers, reduced catalyst usage and reaction energy consumption, simplified purification steps, improved product purity and production safety, and reduced costs.
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Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the field of liquid crystal display materials, more particularly, it relates to a high-efficiency catalytic hydrogenation method of difluorophenyl ether derivative. BACKGROUND
[0002] With the rapid development of display technology, the performance of liquid crystal material as the core component of liquid crystal panel directly affects the key indicators such as brightness, contrast ratio and response speed of the display. Difluorophenyl ether derivative liquid crystal monomer has important application value in negative liquid crystal composition due to its excellent dielectric anisotropy and low temperature mutual solubility. Among them, trans-1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexyl)-benzene can significantly improve the response speed and temperature stability of liquid crystal material due to its high molecular linearity and suitable clearing point.
[0003] Currently, the synthesis of such compounds is mainly realized by catalytic hydrogenation of alkenyl intermediates. The existing technology generally uses palladium on carbon (Pd / C) as a catalyst for hydrogenation reduction in toluene or ethanol solvent. For example, the hydrogenation method disclosed in the same company's patent CN119060739A reacts at 3-4 MPa hydrogen pressure and 50-60℃ for 20 hours, which can achieve complete conversion of the raw material, but has obvious defects. That is, the stereoselectivity is poor, and the reaction generates a mixture of syn / anti isomers, of which the trans isomer accounts for less than 80%, and an additional purification step is required to meet the high purity requirements of liquid crystal materials; the process conditions are harsh, requiring high temperature and high pressure environment and long reaction time, which increases energy consumption and safety risk; the catalyst efficiency is low, the Pd / C dosage is high, and there is a lack of stereodirectional control means. Therefore, developing a method for high selectivity and high efficiency hydrogenation under mild conditions has become a key technical bottleneck to improve the quality of difluorophenyl ether derivative liquid crystal monomer. SUMMARY
[0004] In order to solve the above problems, the present application provides a high-efficiency catalytic hydrogenation method of difluorophenyl ether derivative, which uses existing raw materials and equipment, and significantly improves the stereoselectivity and raw material conversion efficiency of the hydrogenation reaction by introducing 1-adamantanol as a catalyst. The catalyst has low dosage, high catalytic efficiency, no corrosion to the equipment, effectively solves the technical defects of low yield of trans isomer in traditional process, and has the advantages of safe operation, low cost and high product purity.
[0005] To achieve the above purpose, the present application provides the following technical scheme:
[0006] A high-efficiency catalytic hydrogenation method of difluorophenyl ether derivative, comprising the following steps:
[0007] The compound shown in formula (I) is obtained by using 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexenyl)-benzene as raw material, adding a catalyst and 1-adamantanol under the atmosphere of hydrogen in an organic solvent, and reacting at a pressure of 0.2-4 MPa and a temperature of 10-50 DEG C for 3-18 hours. (I)
[0008] Preferably, the catalyst is Pd / C with a loading of 0.5%-10%.
[0009] Preferably, the mass ratio of 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexenyl)-benzene, the catalyst and 1-adamantanol is 1:(0.005-0.1):(0.0001-0.1).
[0010] Preferably, the organic solvent is at least one of dichloromethane, toluene, ethanol and tetrahydrofuran.
[0011] Preferably, the volume ratio of 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexenyl)-benzene and the organic solvent is 1:(2-15).
[0012] Preferably, the hydrogen pressure is 1.5-3 MPa, and the reaction temperature is 35-40 DEG C.
[0013] Preferably, the specific operation comprises: adding 100 g of 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexenyl)-benzene, 400 mL of dichloromethane, 2 g of Pd / C with a loading of 1% wet base and 0.05 g of 1-adamantanol into a reaction kettle, passing hydrogen gas to a pressure of 3 MPa, stirring and reacting at 40 DEG C for 8 hours to obtain the compound shown in formula (I) with a trans isomer ratio of 95%.
[0014] Preferably, when the mass ratio of 1-adamantanol and the raw material is (0.005-0.0005):1, and the hydrogen pressure is 3 MPa, the reaction temperature is 40 DEG C and the reaction time is 8 hours, the trans isomer accounts for ≥90% in the cis-trans isomer mixture in the reaction system, wherein the structure of trans-1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexyl)-benzene is shown in formula (I).
[0015] Compared with the prior art, the present application has the following beneficial effects:
[0016] The present application introduces 1-adamantanol as a synergistic catalyst, its rigid cage-like molecular structure forms a spatial orientation effect at the Pd / C active site, forms a spatial confinement effect, guides the addition of hydrogen atoms from the less hindered side of the cyclohexenyl plane, preferentially generates the thermodynamically stable trans isomer, and the proportion of trans-1-ethoxy-2, 3-difluoro-4-(4-propyl-cyclohexyl)-benzene in the cis-trans isomer mixture is broken through, and the product purity defect caused by the lack of selectivity in the traditional process is completely solved, and the high-energy isomer separation step is eliminated. At the same time, 1-adamantanol optimizes the electronic state of the catalyst, realizes the complete conversion of the raw material at very low load, greatly reduces the amount and cost of palladium metal, and through the regulation of the reaction path, the process conditions are mild, and efficient conversion is completed at low pressure, medium temperature and short reaction time, which significantly reduces the safety risk and energy consumption of the equipment. In addition, the wide compatibility of the additive to conventional organic solvents and the non-corrosive properties ensure the universality and stability of industrial production, and finally obtain high-purity liquid crystal monomers, which comprehensively improves the product performance and economic value. DETAILED DESCRIPTION
[0017] The technical solutions in the embodiments of the present application will be clearly and completely described below in combination with the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative labor belong to the scope of protection of the present application.
[0018] In the following examples, the experimental methods are conventional methods unless otherwise specified, and the test materials used are commercially available from conventional biochemical reagent stores unless otherwise specified. In the quantitative test in the following examples, three repeated experiments are set, and the data is the average value or average value ± standard deviation of three repeated experiments.
[0019] The structural formula of the product difluorophenyl ether derivative liquid crystal monomer 1-ethoxy-2, 3-difluoro-4-(4-propyl-cyclohexenyl)-benzene of the present application is:
[0020]
[0021] Compound molecular formula: C 17 H 24 OF2
[0022] Compound molecular weight: 282.37 g / moL, prepared by the company itself;
[0023] 1-adamantanol, purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., CAS No. 768-95-6;
[0024] Pd / C, purchased from Hubei Shisun Biotechnology Co., Ltd., CAS No.7440-05-3.
[0025] Example 1
[0026] A method for efficient catalytic hydrogenation of a difluorobenzene ether derivative, comprising the following steps:
[0027] In a 1L hydrogenation kettle, 100g of 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexenyl)-benzene and 400mL of dichloromethane were sequentially added, the stirring device was turned on, and the raw material was fully dissolved and dispersed in the solvent. Subsequently, 2g of 1% Pd / C catalyst wet base and 0.05g of 1-adamantanol were added to the reaction kettle, the reaction kettle was closed and sealed, hydrogen was introduced, the pressure was adjusted to 3MPa, the temperature control of the reaction kettle was set to 40℃, and the stirring reaction was continued for 8 hours. After the reaction was completed, the hydrogen supply was stopped and the temperature was cooled to room temperature. The solid catalyst was separated by vacuum filtration, and the filtrate was subjected to rotary evaporation to recover the solvent. A cis-trans isomer mixture of 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexyl)-benzene was obtained. Gas chromatography analysis showed that the conversion rate of the raw material was 100%, the cis-trans isomer ratio was 5:95, and the trans isomer accounted for 95% in the mixture.
[0028] Example 2
[0029] A method for efficient catalytic hydrogenation of a difluorobenzene ether derivative, comprising the following steps:
[0030] In a 1L hydrogenation kettle, 100g of 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexenyl)-benzene and 400mL of dichloromethane were sequentially added, the stirring device was turned on, and the raw material was fully dissolved and dispersed in the solvent. Subsequently, 2g of 1% Pd / C catalyst wet base and 0.05g of 1-adamantanol were added to the reaction kettle, the reaction kettle was closed and sealed, hydrogen was introduced, the pressure was adjusted to 3MPa, the temperature control of the reaction kettle was set to 40℃, and the stirring reaction was continued for 8 hours. After the reaction was completed, the hydrogen supply was stopped and the temperature was cooled to room temperature. The solid catalyst was separated by vacuum filtration, and the filtrate was subjected to rotary evaporation to recover the solvent. A cis-trans isomer mixture of 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexyl)-benzene was obtained. Gas chromatography analysis showed that the conversion rate of the raw material was 100%, the cis-trans isomer ratio was 5:95, and the trans isomer accounted for 95% in the mixture.
[0031] Example 3
[0032] A method for efficient catalytic hydrogenation of a difluorobenzene ether derivative, comprising the following steps:
[0033] In a 1L hydrogenation kettle, 100g of 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexenyl)-benzene and 400mL of dichloromethane were sequentially added, the stirring device was turned on, and the raw material was fully dissolved and dispersed in the solvent. Then, 1g of Pd / C catalyst with a loading of 1% was added to the reaction kettle, the reaction kettle was closed and sealed, hydrogen was introduced, the pressure was adjusted to 0.8MPa, the temperature control of the reaction kettle was set to 35℃, and the stirring reaction was continued for 8 hours. After the reaction was completed, the hydrogen supply was stopped and the temperature was cooled to room temperature. The solid catalyst was separated by vacuum filtration, and the filtrate was subjected to rotary evaporation to recover the solvent. A mixture of cis-trans isomers of 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexyl)-benzene was obtained. Gas chromatography analysis showed that the conversion rate of the raw material was 100%, the cis-trans isomer ratio was 55:45, and the trans isomer accounted for 45% in the mixture.
[0034] Example 4
[0035] A high-efficiency catalytic hydrogenation method for a difluorobenzene ether derivative includes the following steps:
[0036] In a 1L hydrogenation kettle, 100g of 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexenyl)-benzene and 400mL of dichloromethane were sequentially added, the stirring device was turned on, and the raw material was fully dissolved and dispersed in the solvent. Then, 1g of Pd / C catalyst with a loading of 1% was added to the reaction kettle, the reaction kettle was closed and sealed, hydrogen was introduced, the pressure was adjusted to 0.8MPa, the temperature control of the reaction kettle was set to 35℃, and the stirring reaction was continued for 8 hours. After the reaction was completed, the hydrogen supply was stopped and the temperature was cooled to room temperature. The solid catalyst was separated by vacuum filtration, and the filtrate was subjected to rotary evaporation to recover the solvent. A mixture of cis-trans isomers of 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexyl)-benzene was obtained. Gas chromatography analysis showed that the conversion rate of the raw material was 100%, the cis-trans isomer ratio was 55:45, and the trans isomer accounted for 45% in the mixture.
[0037] Example 5
[0038] A high-efficiency catalytic hydrogenation method for a difluorobenzene ether derivative includes the following steps:
[0039] In a 1L hydrogenation kettle, 100g of 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexenyl)-benzene and 400mL of dichloromethane were sequentially added, the stirring device was turned on, and the raw material was fully dissolved and dispersed in the solvent. Subsequently, 2g of 1% Pd / C catalyst wet base and 0.05g of 1-adamantanol were added to the reaction kettle, the reaction kettle was closed and sealed, hydrogen was introduced, the pressure was adjusted to 2MPa, the temperature control of the reaction kettle was set to 35℃, and the stirring reaction was continued for 8 hours. After the reaction was completed, the hydrogen was stopped and cooled to room temperature, the solid catalyst was separated by vacuum filtration, and the filtrate was subjected to rotary evaporation to recover the solvent to obtain a cis-trans isomer mixture of 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexyl)-benzene. Gas chromatography analysis showed that the conversion rate of the raw material was 100%, the cis-trans isomer ratio was 25:75, and the trans isomer accounted for 75% in the mixture.
[0040] Example 6
[0041] A method for efficiently catalyzing the hydrogenation of a difluorophenyl ether derivative, comprising the following steps:
[0042] In a 1L hydrogenation kettle, 100g of 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexenyl)-benzene and 400mL of dichloromethane were sequentially added, the stirring device was turned on, and the raw material was fully dissolved and dispersed in the solvent. Subsequently, 2g of 1% Pd / C catalyst wet base and 0.05g of 1-adamantanol were added to the reaction kettle, the reaction kettle was closed and sealed, hydrogen was introduced, the pressure was adjusted to 2MPa, the temperature control of the reaction kettle was set to 35℃, and the stirring reaction was continued for 8 hours. After the reaction was completed, the hydrogen was stopped and cooled to room temperature, the solid catalyst was separated by vacuum filtration, and the filtrate was subjected to rotary evaporation to recover the solvent to obtain a cis-trans isomer mixture of 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexyl)-benzene. Gas chromatography analysis showed that the conversion rate of the raw material was 100%, the cis-trans isomer ratio was 25:75, and the trans isomer accounted for 75% in the mixture.
[0043] The above is only an example and description of the present application, and those skilled in the art can make various modifications or supplements to the described specific embodiments or use similar methods to replace them, as long as they do not deviate from the invention or exceed the scope defined by the present claims, and should belong to the protection scope of the present application.
Claims
1. A process for the efficient catalytic hydrogenation of difluorophenetole derivatives, characterized in that, The method comprises the following steps: A mixture of 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexenyl)-benzene as raw material, under the atmosphere of hydrogen, with the addition of catalyst and 1-adamantanol, at a pressure of 0.2-4 MPa, at a temperature of 10-50℃, for 3-18 hours, to obtain a mixture of cis-trans isomers of the compound shown in formula (I); (I).
2. The process for the efficient catalytic hydrogenation of difluorobenzene ether derivatives according to claim 1, characterized in that, The catalyst is Pd / C with a loading of 0.5%-10%.
3. The process for the efficient catalytic hydrogenation of difluorobenzene ether derivatives according to claim 1, characterized in that, The mass ratio of the 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexenyl)-benzene, the catalyst and the 1-adamantanol is 1:(0.005-0.1):(0.0001-0.1).
4. The process for the efficient catalytic hydrogenation of difluorobenzene ether derivatives according to claim 1, characterized in that, The organic solvent is at least one of dichloromethane, toluene, ethanol and tetrahydrofuran.
5. The process for the efficient catalytic hydrogenation of difluorobenzene ether derivatives according to claim 1, characterized in that, The volume ratio of the 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexenyl)-benzene and the organic solvent is 1:(2-15).
6. The process for the efficient catalytic hydrogenation of difluorobenzene ether derivatives according to claim 1, characterized in that, The hydrogen pressure is 1.5-3 MPa, and the reaction temperature is 35-40 DEG C.
7. The process for the efficient catalytic hydrogenation of difluorobenzene ether derivatives according to claim 1, characterized in that, The specific operation comprises: adding 100 g of 1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexenyl)-benzene, 400 mL of dichloromethane, 2 g of Pd / C with a loading of 1% wet base and 0.05 g of 1-adamantanol into a reaction kettle, passing hydrogen gas to a pressure of 3 MPa, stirring and reacting at 40 DEG C for 8 hours to obtain a compound of formula (I) with a trans isomer ratio of 95%.
8. The process for the high efficient catalytic hydrogenation of difluorophenethere derivatives according to any one of claims 1 to 7, characterized in that, When the mass ratio of the 1-adamantanol and the raw material is (0.005-0.0005):1, the hydrogen pressure is 3 MPa, the reaction temperature is 40 DEG C and the reaction time is 8 h, the trans isomer in the cis-trans isomer mixture in the reaction system is ≥90%, wherein the structure of the trans-1-ethoxy-2,3-difluoro-4-(4-propyl-cyclohexyl)-benzene is shown in formula (I).