Synthesis method of substituted trans-dicyclohexyl alkenyl liquid crystal monomer
By using bicyclohexyl ketone reaction with chloromethyl etherphosphine salt and hydroxylamine hydrochloride, combined with the selective deprotection and transposition reaction of the bicatalyst, the problem of selective Wittig reaction and deprotection control in the prior art was solved, and the efficient and low-cost synthesis of 4,4’-bicyclohexyldiene was achieved.
Patent Information
- Application Number
- CN202411924261.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-25
- Publication Date
- 2025-03-11
AI Technical Summary
The existing methods for synthesizing 4,4’-bicyclohexyldiene compounds have the problem of selective Wittig reactions and the difficulty of deprotection control of monoketals, resulting in impurity in products and difficulty in large-scale industrial production.
Using 4,4’-bicyclohexyl ketone as the starting material, 4,4’-bicyclohexyldiene methyl ether was formed by reacting with chloromethyl ether phosphine salt, and then reacting with hydroxylamine hydrochloride to form 4,4’-bicyclohexyldioxime, and unilateral selective deprotection was achieved through a bicatalyst. Finally, transbicyclohexylene liquid crystal monomer was obtained through an index reaction.
The synthesis of 4,4’-bicyclohexyldiene with high purity and high total yield has been achieved, reducing production costs and is suitable for large-scale industrial production.
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Abstract
Description
Technical Field
[0001] The invention belongs to the field of organic synthesis, and in particular relates to a method for synthesizing a substituted trans-bicyclohexylene liquid crystal monomer. Background Art
[0002] In the field of organic synthesis, dicyclohexyl diene compounds have attracted extensive attention due to their unique chemical structure and potential application value. These compounds have important application prospects in many fields such as material science and drug development. For example, in liquid crystal materials, dicyclohexyl diene compounds can improve the physical properties of liquid crystals, such as improving the stability and response speed of liquid crystals.
[0003] The method of synthesizing 4,4'-dicyclohexyl diene compounds is one of the research hotspots in this field. At present, the main synthesis route is to gradually build the molecular structure of the target compound through a series of chemical reactions. Among them, the Wittig reaction, as one of the key steps, plays an important role in the synthesis of carbon-carbon double bonds. At the same time, the protection and deprotection operations of ketal are also essential links in the synthesis process to ensure the selectivity of the reaction and the purity of the product.
[0004] Existing synthetic route 1 is as follows:
[0005]
[0006] The method comprises: step 1, reacting 4,4'-bicyclohexyl ketone monoketal with chloromethyl ether phosphonium salt to prepare 4,4'-bicyclohexyl enol monoketal; step 2, performing acid deprotection; step 3, performing isomerization operation; step 4, reacting with bromomethyl phosphonium salt; step 5, reacting with chloromethyl ether phosphonium salt to obtain 4,4'-bicyclohexyl enol ether ethylene; step 6, further performing acid hydrolysis; step 7, performing isomerization; step 8, reacting with bromoethyl phosphonium salt; and step 9, performing transposition to obtain 4-ethylene-4'-propylene-bicyclohexane.
[0007] Synthesis route 1 has the following problems: In step 4, the method faces the problem of selective Wittig reaction of aldehydes and ketones. In this step, due to the complexity of the reaction system and the similarity of the aldehyde and ketone structures, it is difficult to achieve a selective Wittig reaction of aldehydes and ketones. This results in the presence of multiple isomers and by-products in the reaction products, making it difficult to obtain a high-purity target product. Since the problem of selective Wittig reaction cannot be solved, this method is difficult to apply in large-scale industrial production, because mass production requires high-purity products and a stable reaction process.
[0008] Existing synthetic route 2 is as follows:
[0009]
[0010] The method comprises: step 1, reacting 4,4'-dicyclohexyl ketone monoketal with chloromethyl ether phosphonium salt to prepare 4,4'-dicyclohexyl enol ether monoketal; step 2, performing acid deprotection; step 3, performing Wittig reaction with phosphonium salt A to obtain 4-alkylene-4'-dicyclohexyl monoketal; step 4, performing deprotection operation; step 5, reacting with chloromethyl ether phosphonium salt to obtain 4-alkylene-4'-dicyclohexyl enol ether; step 6, performing acid hydrolysis and deprotection again; step 7, performing Wittig reaction with phosphonium salt B; and step 8, performing transposition to obtain the final product 4,4'-dicyclohexyl diene.
[0011] The following problems exist in synthetic route 2: In step 2, there is a deprotection problem of the monoketal. The deprotection process of the monoketal is difficult to fully control, resulting in incomplete deprotection or excessive deprotection. Due to the incomplete deprotection of the monoketal, the selectivity of the subsequent Wittig reaction is seriously affected. The incompletely deprotected monoketal will participate in the reaction to generate non-target products, resulting in a low overall yield. Similarly, due to the existence of the above-mentioned problems, this method also has obstacles in industrial mass production and cannot meet the requirements of large-scale production, limiting the application of this method in actual production.
[0012] In summary, the existing methods for synthesizing 4,4'-dicyclohexyl diene compounds have the above-mentioned technical problems and cannot achieve efficient, high-purity and large-scale production. Therefore, it is necessary to develop a new synthesis method to solve these problems. Summary of the invention
[0013] The purpose of the present invention is to provide a novel synthetic route for substituted trans-bicyclohexylene liquid crystal monomers. The starting material is cheap and readily available 4,4'-bicyclohexyl ketone, and no transposition and purification are required in the early stage. Only transposition crystallization is required in the last step, and the purity and total yield are high.
[0014] In order to achieve the above object, the present invention provides a method for synthesizing a substituted trans-bicyclohexylene liquid crystal monomer, comprising:
[0015] Step S1, 4,4'-dicyclohexyl ketone is used as a starting material, reacted with chloromethyl ether phosphonium salt and potassium tert-butoxide at -10°C to 0°C to form 4,4'-dicyclohexyl diene methyl ether;
[0016] Step S2, 4,4'-dicyclohexyldiolefin methyl ether and hydroxylamine hydrochloride react under the action of a first catalyst to generate 4,4'-dicyclohexyldioxime; the first catalyst comprises: diatomaceous earth, silica gel, methanesulfonic acid and morpholine;
[0017] Step S3, 4,4'-dicyclohexyldioxime is unilaterally deprotected under the action of a second catalyst to generate 4-oxime-4'-dicyclohexylcarboxaldehyde; the second catalyst comprises: diatomaceous earth, silica gel, methanesulfonic acid and tetrahydropyrrole;
[0018] Step S4, 4-oxime-4'-bicyclohexylcarboxaldehyde reacts with R1BrPPh3 and potassium tert-butoxide at -10°C to 0°C to obtain 4-oxime-4'-bicyclohexylalkylethylene 2; wherein R1 is a C1-C5 alkyl group;
[0019] Step S5, 4-oxime-4'-dicyclohexylalkylethylene 2 reacts with formic acid to generate 4-formaldehyde-4'-dicyclohexylalkylethylene 3;
[0020] Step S6, 4-formaldehyde-4'-dicyclohexylalkylethylene 3 reacts with R2BrPPh3 and potassium tert-butoxide at -10°C to 0°C to obtain a cis-trans mixture 4; wherein R2 is a C1-C5 alkyl group;
[0021] Step S7, the cis-trans mixture 4 is transposed under the action of sodium benzenesulfinate and dilute sulfuric acid to form a substituted trans-bicyclohexylene liquid crystal monomer 1.
[0022] Optionally, in step S2, the mass ratio of the first catalyst to 4,4'-dicyclohexyl ketone is (0.1-0.5):1.
[0023] Optionally, in the first catalyst, the mass ratio of diatomaceous earth, silica gel, methanesulfonic acid and morpholine is (3-5): (3-5): 1:1.
[0024] Optionally, in step S2, the molar ratio of hydroxylamine hydrochloride to 4,4'-dicyclohexyl ketone is (2-2.5):1.
[0025] Optionally, triethylamine is further added in step S2, and the molar ratio of triethylamine to 4,4'-dicyclohexyl ketone is (2-2.5):1.
[0026] Optionally, in step S3, the mass ratio of the second catalyst to 4,4'-dicyclohexyl ketone is (0.1-0.5):1.
[0027] Optionally, in the second catalyst, the mass ratio of diatomaceous earth, silica gel, methanesulfonic acid and tetrahydropyrrole is (5-15): (5-15): (3-5): 1.
[0028] Optionally, in step S3, the reaction temperature is between 30 and 60°C.
[0029] Optionally, in step S5, the mass ratio of formic acid to 4,4'-dicyclohexyl ketone is (0.5-2):1.
[0030] Optionally, in step S5, the reaction temperature is between 50°C and 80°C.
[0031] Compared with the prior art, the technical solution of the present invention has the following beneficial effects:
[0032] The invention uses 4,4'-dicyclohexyl ketone as a starting raw material, which is cheap and easy to obtain, so that the cost is controllable; a first catalyst is used to promote the reaction of 4,4'-dicyclohexyl diene methyl ether and hydroxylamine hydrochloride to form 4,4'-dicyclohexyl dioxime, the reaction is complete, and the next step of reaction can be entered without post-treatment; then a second catalyst is used to achieve unilateral selective deprotection to obtain 4-oxime-4'-dicyclohexyl formaldehyde, which has less by-products and high yield; 4-oxime-4'-dicyclohexyl formaldehyde reacts with R1BrPPh3 to obtain 4-oxime-4'-dicyclohexyl alkyl olefin; then formic acid is used to remove the other side protection, and the product reacts with R2BrPPh3 to obtain the final product 4,4'-dicyclohexyl diene, and then a trans product is obtained through a transposition reaction.
[0033] Furthermore, the present invention comprises seven steps of reaction, and no transposition and purification are required in the early stage, and only the last step of transposition and crystallization is required, and the total yield can reach more than 70%. Moreover, the cost (or market price) of the starting raw material 4,4'-dicyclohexyl ketone is generally lower than that of the corresponding 4,4'-dicyclohexyl ketone monoacetal; therefore, the overall cost of the present invention is lower than the conventional method for preparing trans-dicyclohexyl diene in the prior art. DETAILED DESCRIPTION
[0034] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0035] The "C1-C5 alkyl" described herein refers to an alkyl group containing 1-5 carbon atoms, including methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, etc., and R1 and R2 may be the same or different.
[0036] The present invention uses 4,4'-dicyclohexyldione as a starting material, firstly performs a wittig reaction with chloromethyl ether phosphonium salt to obtain 4,4'-dicyclohexyl diene methyl ether, then reacts with hydroxylamine hydrochloride under the action of a first catalyst to prepare 4,4'-dicyclohexyl dioxime, and then selectively removes one side of the protection with a second catalyst to obtain 4-oxime-4'-dicyclohexyl formaldehyde, and reacts with phosphonium salt A (R1BrPPh3) to obtain 4-oxime-4'-dicyclohexyl alkyl olefin. Then, the other side of the protection is removed with formic acid, and reacts with phosphonium salt B (R2BrPPh3) to obtain the final product 4,4'-dicyclohexyl diene, and then a trans product is obtained through a transposition reaction. The corresponding synthetic route of the present invention is as follows:
[0037]
[0038] A method for synthesizing a substituted trans-bicyclohexylene liquid crystal monomer of the present invention comprises:
[0039] Step S1, 4,4'-dicyclohexyl ketone is used as a starting material, and reacts with chloromethyl ether phosphonium salt and potassium tert-butoxide at -10°C to 0°C to form 4,4'-dicyclohexyl diene methyl ether.
[0040] In step S2, 4,4'-dicyclohexyldiolefin methyl ether and hydroxylamine hydrochloride react with a first catalyst to generate 4,4'-dicyclohexyldioxime; the first catalyst comprises diatomaceous earth, silica gel, methanesulfonic acid and morpholine.
[0041] In some embodiments, the mass ratio of the first catalyst to 4,4'-dicyclohexyl ketone is (0.1-0.5): 1. In the first catalyst, the mass ratio of diatomaceous earth, silica gel, methanesulfonic acid and morpholine is (3-5): (3-5): 1:1.
[0042] In some embodiments, the molar ratio of hydroxylamine hydrochloride to 4,4'-dicyclohexyl ketone is (2-2.5):1.
[0043] In some embodiments, triethylamine is further added in step S2, and the molar ratio of triethylamine to 4,4'-dicyclohexyl ketone is (2-2.5): 1. The triethylamine promotes the reaction and can react with hydroxylamine hydrochloride to release hydroxylamine.
[0044] The solvents that can be used in step S2 include various liquid alkanes (e.g., n-hexane), cycloalkanes (e.g., cyclohexane), halogenated alkanes (e.g., dichloromethane), alkylbenzenes (e.g., toluene, etc.), etc.; the amount of the solvent used needs to be sufficient to fully dissolve the product.
[0045] The operation process of step S2 is: first add the solvent and 4,4'-dicyclohexyldiolefin methyl ether, hydroxylamine hydrochloride, and the first catalyst into the reaction container, stir and heat to between 60°C and 100°C under nitrogen protection, maintain stirring and liquid temperature between 60°C and 100°C, dropwise add triethylamine, and keep the liquid temperature at 60°C to 100°C and continue stirring and reacting for 2-3 hours after the dropwise addition. Filter by suction, wash the filtrate with water three times, separate the liquids, and concentrate to remove the solvent to obtain 4,4'-dicyclohexyldioxime.
[0046] Step S3, 4,4'-dicyclohexyldioxime is unilaterally deprotected under the action of a second catalyst to generate 4-oxime-4'-dicyclohexylcarboxaldehyde; the second catalyst comprises: diatomaceous earth, silica gel, methanesulfonic acid and tetrahydropyrrole.
[0047] In some embodiments, the mass ratio of the second catalyst to 4,4'-dicyclohexyl ketone is (0.1-0.5): 1. In the second catalyst, the mass ratio of diatomaceous earth, silica gel, methanesulfonic acid and tetrahydropyrrole is (5-15): (5-15): (3-5): 1.
[0048] If the reaction temperature of step S3 is too low, the reaction will not occur. If the temperature is too high, the oxime on the other side will also be deprotected, which will reduce the selectivity. In this example, the reaction temperature is between 30°C and 60°C.
[0049] Experiments have shown that if other acids are used for deprotection without using a second catalyst, the selectivity of deprotection cannot be controlled. The reaction equations for deprotection using an acid (such as formic acid) are compared as follows:
[0050] It can be seen that the use of acid deprotection will produce a large number of by-products, such as products of simultaneous deprotection on both sides.
[0051] The amount of solvent used in step S3 needs to make the reaction product not too viscous. The specific solvent type can be toluene, tetrahydrofuran, 1,4-dioxane, nitromethane, or a mixture thereof.
[0052] The operation process of step S3 is: add 4,4'-dicyclohexyldioxime, toluene, tetrahydrofuran, the second catalyst, and pure water in the previous step into a reaction container, stir and control the temperature to between 30°C and 60°C under nitrogen protection, and after the reaction is completed, filter out the solid, separate the liquid, wash with water, and concentrate to obtain a crude product of 4-oxime-4'-dicyclohexylformaldehyde.
[0053] Step S4, 4-oxime-4'-bicyclohexylcarboxaldehyde reacts with R1BrPPh3 and potassium tert-butoxide at -10°C to 0°C to obtain 4-oxime-4'-bicyclohexylalkylethylene 2; wherein R1 is a C1-C5 alkyl.
[0054] Step S5, 4-oxime-4'-dicyclohexylalkylethylene 2 reacts with formic acid to generate 4-formaldehyde-4'-dicyclohexylalkylethylene 3.
[0055] The amount of solvent required for step S5 is sufficient to make the reaction mixture not too viscous and easy to stir evenly, for example, the amount of solvent is above 5V; the specific solvent type can be toluene, halogenated benzene, 1,4-dioxane, nitromethane, or a mixture thereof, etc.
[0056] In some embodiments, in step S5, the mass ratio of formic acid to 4,4'-dicyclohexyl ketone is (0.5-2): 1. The reaction temperature is 50°C to 80°C.
[0057] Step S6, 4-formaldehyde-4'-dicyclohexylalkylethylene 3 reacts with R2BrPPh3 and potassium tert-butoxide at -10°C to 0°C to produce a cis-trans mixture 4; wherein R2 is a C1-C5 alkyl group.
[0058] Step S7, the cis-trans mixture 4 is transposed under the action of sodium benzenesulfinate and dilute acid to form a substituted trans-bicyclohexylene liquid crystal monomer 1.
[0059] In some embodiments, the dilute acid may be dilute sulfuric acid or dilute hydrochloric acid.
[0060] The following is a further description of the synthesis method of an asymmetric trans-bicyclohexyl diene liquid crystal monomer (eg, trans-4-ethylene-4'-propylene-bicyclohexyl alkane) of the present invention in conjunction with an example. Unless otherwise specified, the raw materials and reagents used in this example are all commercially available.
[0061] Example
[0062] The first stage synthesis route is as follows:
[0063]
[0064] Referring to reaction 1-3, first add 200ml of tetrahydrofuran and 82.2g (0.24mol) of chloromethyl ether phosphonium salt to a 500ml glass three-necked flask, stir and cool to -10℃~0℃ under nitrogen protection. Then, maintain stirring, add 26.8g (0.24mol) of potassium tert-butoxide to the reaction flask in batches, and control the temperature of the reaction liquid to be between -10℃~0℃; after adding, continue to keep warm and stir for 0.5 hours, and then, while stirring and keeping warm at -10℃~0℃, add 19.4g (0.1mol) of 4,4'-bicyclohexyl dione and 50ml of toluene to the reaction container; after dropping, continue to keep warm and stir for 1 hour. Slowly add the above reaction solution to 90g (5mol) of tap water, stirring while adding, and control the water temperature between 0℃~30℃. After adding, continue to stir for 10 minutes, let stand, and separate. The organic layer was washed with water and separated several times until the pH value of the aqueous layer reached 7, then the solvent was removed by concentration, 100 ml of petroleum ether was added, stirred and extracted, and filtered; the filter cake was stirred and extracted with 100 ml of petroleum ether again, the organic phases of the two extractions were combined, passed through a 10 g silica gel column, flushed with 50 ml of petroleum ether, and the filtrate was concentrated to obtain the crude product of 4,4'-dicyclohexyl diene methyl ether.
[0065] Preparation of catalyst 1 (first catalyst): In a 500 ml beaker, add 20 g diatomaceous earth, 20 g silica gel (800-1000 mesh), 5 g methanesulfonic acid, 5 g morpholine, stir evenly with a glass rod, transfer to an oven, bake at 120°C for 6 hours, cool and protect with nitrogen for standby use.
[0066] Referring to reaction 1-4, add the crude product (0.1 mol) of 4,4'-dicyclohexyl diolefin methyl ether from the previous step, 100 ml of toluene, 100 ml of 1,4-dioxane, 16.7 g (0.24 mol) of hydroxylamine hydrochloride, and 5 g of the above-prepared catalyst 1 to another 500 ml glass three-necked flask. Under nitrogen protection, stir and control the temperature to 60°C to 100°C, and add 24.2 g (0.24 mol) of triethylamine dropwise. After the reaction, cool the reaction solution to room temperature, filter, and wash the filtrate with 50 ml of water each time, three times in total, and finally concentrate to obtain 25 g (0.1 mol) of crude 4,4'-dicyclohexyl dioxime, which can be directly used in the next reaction.
[0067] The second stage synthesis route is as follows:
[0068]
[0069] Preparation of catalyst 2: In a 500 ml beaker, add 50 g diatomaceous earth, 50 g silica gel (800-1000 mesh), 20 g methanesulfonic acid, and 5 g tetrahydropyrrole, stir evenly with a glass rod, transfer to an oven, bake at 120°C-150°C for 6 hours, and protect with nitrogen after cooling.
[0070] Referring to reaction 1-5, first add 4,4'-dicyclohexyldioxime (0.1 mol) from the previous step, 5 g of catalyst 2, 100 ml of toluene, 100 ml of tetrahydrofuran, and 20 g of pure water into a 500 ml glass three-necked flask, stir and control the temperature to between 30°C and 60°C under nitrogen protection, and react for 3-6 hours; filter the reaction solution, separate the liquids, and concentrate the organic layer under reduced pressure to obtain a crude product of 4-oxime-4'-dicyclohexylcarboxaldehyde.
[0071] Referring to reaction 1-6, add 200ml of tetrahydrofuran and 42.8g (0.12mol) of bromomethylphosphonium salt to another 500ml glass three-necked flask, stir and cool to -10℃~0℃ under nitrogen protection. Then maintain stirring, add 13.4g (0.12mol) of potassium tert-butoxide to the reaction flask in batches, and control the temperature of the reaction solution to be between -10℃~0℃; after adding, continue to keep warm and stir for 0.5 hours, then while stirring and keeping warm at -10℃~0℃, add 19.4g (0.1mol) of 4-oxime-4'-dicyclohexylcarboxaldehyde and 100ml of tetrahydrofuran solution to the reaction vessel; after dripping, continue to keep warm and stir for 1 hour. Slowly add the above reaction solution to 90g (5mol) of tap water, stir while adding, and control the water temperature between 0℃~30℃. After the addition is complete, continue stirring for 10 minutes, let stand, and separate the liquids. After the organic layer is washed with water several times until neutral, it is concentrated to remove the solvent, and 100 ml of a mixed solvent (petroleum ether: toluene = 1:1) is added, stirred, extracted, and filtered; the filter cake is stirred and extracted with 100 ml of a mixed solvent (petroleum ether: toluene = 1:1), filtered, and the organic phases of the two extractions are combined, and the filtrate is concentrated to obtain 23.3 g (0.1 mol) of a crude product of 4-oxime-4'-dicyclohexylethylene.
[0072] The synthesis route of the third stage is as follows:
[0073]
[0074] Referring to reaction 1-7, first add 23.3 g (0.1 mol) of the crude 4-oxime-4'-dicyclohexylethylene from the previous step, 20 g of 99% formic acid, and 100 ml of chlorobenzene into a 500 ml glass three-necked flask, stir and control the temperature to between 50°C and 80°C under nitrogen protection, and react for 3-6 hours; separate the liquids, wash the organic layer with water until it is neutral, and then concentrate the organic layer under reduced pressure to obtain a crude 4-formaldehyde-4'-dicyclohexylethylene.
[0075] Referring to reaction 1-8, add 200ml of tetrahydrofuran and 44.5g (0.12mol) of bromoethane phosphonium salt to another 500ml glass three-necked flask, stir and cool to -10℃~0℃ under nitrogen protection. Then, maintain stirring, add 13.4g (0.12mol) of potassium tert-butoxide to the reaction flask in batches, and control the temperature of the reaction liquid to be between -10℃~0℃; after adding, continue to keep warm and stir for 0.5 hours, then add 21.8g (0.1mol) of 4-formaldehyde-4'-dicyclohexylethylene and 100ml of toluene to the reaction container while stirring and keeping warm at -10℃~0℃; after dropping, continue to keep warm and stir for 1 hour. Slowly add the above reaction solution to 90g (5mol) of tap water, stir while adding, and control the water temperature between 0℃~30℃. After the addition is completed, continue stirring for 10 minutes, let stand, and separate the liquids. The organic layer is washed with water and separated several times until the pH value of the water layer reaches 7, then concentrated to remove the solvent, add 100 ml of petroleum ether, stir and extract, and filter; the filter cake is stirred and extracted with 100 ml of mixed solvent petroleum ether, filter, combine the organic phases of the two extractions, pass through a 10 g silica gel column, flush the column with 50 ml of petroleum ether, and concentrate the filtrate to obtain a cis-trans mixture of 4-ethylene-4'-dicyclohexylpropene.
[0076] Referring to reaction 1-9, 23g (0.1mol) of the cis-trans mixture of 4-ethylene-4'-propylene-bicyclohexane in the previous step, 100ml of toluene, 4.9g (0.03mol) of sodium benzenesulfinate, and 7.35g (0.015mol) of 20% dilute sulfuric acid were added to a 500ml glass three-necked flask, and the mixture was stirred and the temperature was controlled to between 80°C and 100°C under nitrogen protection, and the reaction was carried out for 6h-8h; the reaction liquid was filtered, the organic layer was washed with water to neutralize, concentrated under reduced pressure, and recrystallized with 2V ethanol at -15°C to obtain trans-4-ethylene-4'-propylene-bicyclohexane with a yield of 70%. Among them, 2V ethanol means that the volume of ethanol is twice the volume of the recrystallized substance (the organic synthesis product before the recrystallization operation).
[0077] In summary, the synthesis method of the present invention innovatively adopts dual catalysts, wherein the first catalyst makes the reaction fast and complete, and 4,4'-dicyclohexyl diolefin methyl ether is almost completely converted into 4,4'-dicyclohexyl dioxime, and no post-treatment is required, and the next step of removing unilateral protection is directly entered; the second catalyst can selectively remove unilateral protection, reduce by-products, and have a high yield. In addition, the present invention does not require transposition and purification in the early stage, and only requires transposition crystallization in the last step, and the total yield can reach more than 70%.
[0078] Although the content of the present invention has been described in detail through the above preferred embodiments, it should be appreciated that the above description should not be considered as a limitation of the present invention. After reading the above content, it will be apparent to those skilled in the art that various modifications and substitutions of the present invention will occur. Therefore, the protection scope of the present invention should be limited by the appended claims.
Claims
1. A method for synthesizing a substituted trans-bicyclohexylene liquid crystal monomer, characterized in that: The synthetic route is: The method includes: Step S1, 4,4'-dicyclohexyl ketone is used as a starting material, reacted with chloromethyl ether phosphonium salt and potassium tert-butoxide at -10°C to 0°C to form 4,4'-dicyclohexyl diene methyl ether; Step S2, 4,4'-dicyclohexyldiolefin methyl ether and hydroxylamine hydrochloride react under the action of a first catalyst to generate 4,4'-dicyclohexyldioxime; the first catalyst comprises: diatomaceous earth, silica gel, methanesulfonic acid and morpholine; Step S3, 4,4'-dicyclohexyldioxime is unilaterally deprotected under the action of a second catalyst to generate 4-oxime-4'-dicyclohexylcarboxaldehyde; the second catalyst comprises: diatomaceous earth, silica gel, methanesulfonic acid and tetrahydropyrrole; Step S4, 4-oxime-4'-bicyclohexylcarboxaldehyde reacts with R1BrPPh3 and potassium tert-butoxide at -10°C to 0°C to obtain 4-oxime-4'-bicyclohexylalkylethylene (2); wherein R1 is a C1-C5 alkyl group; Step S5, 4-oxime-4'-dicyclohexylalkylethylene (2) reacts with formic acid and undergoes deprotection to generate 4-formaldehyde-4'-dicyclohexylalkylethylene (3); Step S6, 4-formaldehyde-4'-dicyclohexylalkylethylene (3) reacts with R2BrPPh3 and potassium tert-butoxide at -10°C to 0°C to obtain a cis-trans mixture (4); wherein R2 is a C1-C5 alkyl group; Step S7, the cis-trans mixture (4) is transposed under the action of sodium benzenesulfinate and dilute acid to form a substituted trans-bicyclohexylene liquid crystal monomer (1).
2. The method for synthesizing a substituted trans-bicyclohexylene liquid crystal monomer according to claim 1, characterized in that: In step S2, the mass ratio of the first catalyst to 4,4'-dicyclohexyl ketone is (0.1-0.5):
1.
3. The method for synthesizing a substituted trans-bicyclohexylene liquid crystal monomer according to claim 1, characterized in that: In the first catalyst, the mass ratio of diatomaceous earth, silica gel, methanesulfonic acid and morpholine is (3-5): (3-5): 1:
1.
4. The method for synthesizing a substituted trans-bicyclohexylene liquid crystal monomer according to claim 1, characterized in that: In step S2, the molar ratio of hydroxylamine hydrochloride to 4,4'-dicyclohexyl ketone is (2-2.5):
1.
5. The method for synthesizing a substituted trans-bicyclohexylene liquid crystal monomer according to claim 1, characterized in that: Triethylamine is also added in step S2, and the molar ratio of triethylamine to 4,4'-dicyclohexyl ketone is (2-2.5):
1.
6. The method for synthesizing a substituted trans-bicyclohexylene liquid crystal monomer according to claim 1, characterized in that: In step S3, the mass ratio of the second catalyst to 4,4'-dicyclohexyl ketone is (0.1-0.5):
1.
7. The method for synthesizing a substituted trans-bicyclohexylene liquid crystal monomer according to claim 1, characterized in that: In the second catalyst, the mass ratio of diatomaceous earth, silica gel, methanesulfonic acid and tetrahydropyrrole is (5-15): (5-15): (3-5):
1.
8. The method for synthesizing a substituted trans-bicyclohexylene liquid crystal monomer according to claim 1, characterized in that: In step S3, the reaction temperature is between 30 and 60°C.
9. The method for synthesizing a substituted trans-bicyclohexylene liquid crystal monomer according to claim 1, characterized in that: In step S5, the mass ratio of formic acid to 4,4'-dicyclohexyl ketone is (0.5-2):
1.
10. The method for synthesizing a substituted trans-bicyclohexylene liquid crystal monomer according to claim 1, characterized in that: In step S5, the reaction temperature is between 50°C and 80°C.