Synthesis method of trans-4-(trans-4-methylcyclohexyl) cyclohexyl methanol

Abstract

The invention discloses a synthesis method of trans-4-(trans-4-methylcyclohexyl) cyclohexyl methanol, which comprises the following steps: step 1, taking 4, 4 '-biphenyldicarboxylic acid as a raw material, reacting with alkali to form salt, and performing catalytic hydrotreatment and acidification to obtain trans-4, 4'-biphenyldicarboxylic acid; step 2, the trans-4, 4 '-bicyclohexyl dicarboxylic acid is reduced into trans-4-(trans-4-hydroxymethyl cyclohexyl) cyclohexyl methanol under the action of a reducing agent, and the trans-4, 4'-bicyclohexyl dicarboxylic acid is reduced into the trans-4-(trans-4-hydroxymethyl cyclohexyl) cyclohexyl methanol under the action of a reducing agent; step 3, carrying out mono-esterification on the trans-4-(trans-4-hydroxymethyl cyclohexyl) cyclohexyl methanol, so as to form trans-4-(trans-4-hydroxymethyl cyclohexyl) cyclohexyl methanesulfonate; and step 4, reducing the trans-4-(trans-4-hydroxymethyl cyclohexyl) cyclohexyl methanesulfonate through lithium aluminum hydride, so as to obtain the trans-4-(trans-4-methyl cyclohexyl) cyclohexyl methanol. The designed route is unique, the raw materials are cheap and easy to obtain, the process conditions are reasonable, the product quality and cost are controllable, the total yield can reach 75% or above, aftertreatment is simple, isomerization is not needed, and the trans-98% or above product can be obtained.

Description

Technical Field

[0001] The invention belongs to the field of organic compound synthesis, and in particular relates to a method for synthesizing trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol. Background Art

[0002] As an important organic compound, trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol has a wide range of applications in many fields such as medicine, fragrances, cosmetics and fine chemicals. For example, trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol can be used as an intermediate for liquid crystal materials. Liquid crystal materials have important applications in the display field, such as liquid crystal displays (LCDs). Trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol can be used as an important intermediate for the synthesis of diene polycyclic system liquid crystals. Other functional groups are introduced through a series of chemical reactions to synthesize liquid crystal materials with specific properties. These liquid crystal materials can present different liquid crystal phases under different temperature and electric field conditions, realizing light modulation and display functions.

[0003] There are relatively few literatures and patents on the synthesis of trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol at home and abroad.

[0004] Patent CN1450040A uses trans-4-(trans-4'-alkylcyclohexyl)cyclohexylcarboxylic acid as raw material and adopts lithium aluminum hydride reduction method to prepare trans-4-(trans-4'-alkylcyclohexyl)cyclohexylmethanol. However, the source of trans-4-(trans-4'-methylcyclohexyl)cyclohexylcarboxylic acid is unstable (almost no supply in the market) and the price is high, making the cost of synthesizing trans-4-(trans-4'-methylcyclohexyl)cyclohexylmethanol uncontrollable.

[0005] Patent CN112961042A utilizes anti-4-(anti-4'-alkylcyclohexyl) cyclohexylcarboxylic acid or its ester to carry out reduction reaction under reducing agent, catalyst or co-catalyst and solvent conditions to prepare anti-4-(anti-4'-alkylcyclohexyl) cyclohexylmethanol. However, this method has a key premise assumption, that is, anti-4-(anti-4'-alkylcyclohexyl) cyclohexylcarboxylic acid or its ester is easy to obtain and cheap. But the actual situation is that anti-4-(anti-4'-methylcyclohexyl) cyclohexylcarboxylic acid or its ester not only has high raw material prices, but also is difficult to find a stable supplier. This results in that in the actual production process, the instability of raw material supply can seriously affect production plan and product cost, and cannot meet the needs of large-scale industrial production. Summary of the invention

[0006] The invention aims to provide a novel synthesis method of trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol, wherein the main raw material used is of stable source, cheap and easily available, the reaction process is sufficient, the post-treatment is relatively simple, the product purity is good, and the total yield is high.

[0007] In order to achieve the above object, the present invention provides a method for synthesizing trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol, which comprises:

[0008] Step 1, using 4,4'-biphenyldicarboxylic acid as a raw material, reacting with a base to form a salt, and then subjecting to catalytic hydrogenation treatment and acidification to obtain trans, trans-4,4'-bicyclohexyldicarboxylic acid;

[0009] Step 2, trans, trans-4,4'-bicyclohexyl dicarboxylic acid is reduced to trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol under the action of a reducing agent;

[0010] Step 3, trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol reacts with sulfonyl chloride to form trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexyl methanesulfonate through monoesterification;

[0011] Step 4, trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexyl methanesulfonate is reduced with lithium aluminum hydride to obtain trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol.

[0012] Optionally, in step 1, the molar ratio of the base to 4,4'-biphenyldicarboxylic acid is (2.1-2.2):1, and the base is at least one of sodium hydroxide, potassium hydroxide, sodium tert-butoxide and potassium tert-butoxide.

[0013] Optionally, in step 1, the catalyst for catalytic hydrogenation is a mixture of ruthenium alumina and platinum alumina, wherein the ruthenium content in the ruthenium alumina is 3%-10% by mass, and the platinum content in the platinum alumina is 1%-5% by mass; the amount of the catalyst and 4,4'-biphenyldicarboxylic acid used is 2%-5% by mass.

[0014] Optionally, in step 1, the hydrogenation pressure is 1MPa-3MPa, and the hydrogenation temperature is 50°C to 80°C.

[0015] Optionally, the acidified pH value is 1-2.

[0016] Optionally, in step 2, the reducing agent is an aluminum trichloride complex of lithium aluminum hydride, wherein the amount of the aluminum trichloride complex of lithium aluminum hydride and trans, trans-4,4'-bicyclohexyl dicarboxylic acid is in a molar ratio of (1.8-2.0):1.

[0017] In step 2, the reducing agent is a mixture of sodium borohydride and anhydrous zinc chloride, wherein the molar ratio of sodium borohydride to trans, trans-4,4'-bicyclohexyl dicarboxylic acid is (2.2-2.4):1, and the molar ratio of anhydrous zinc chloride to trans, trans-4,4'-bicyclohexyl dicarboxylic acid is (2.2-2.4):1.

[0018] In step 3, the molar ratio of the sulfonyl chloride to trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol is (1.0-1.05):1, and the sulfonyl chloride is at least one of p-toluenesulfonyl chloride, methanesulfonyl chloride and benzenesulfonyl chloride; the reaction solvent includes a chlorine-containing solvent, and the chlorine-containing solvent includes dichloromethane and / or chloroform.

[0019] In step 3, an acid binding agent is also added, and the molar ratio of the acid binding agent to trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol is (1.05-1.1):1, wherein the acid binding agent is at least one of triethylamine, pyridine, diisopropylamine and ethyldiisopropylamine.

[0020] In step 4, the amount of lithium aluminum hydride and trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexyl methanesulfonate is (1.2-2.0) in a molar ratio of 1:1, the reaction temperature is -20°C to -10°C, and the reaction solvent is an ether solvent, which is at least one of diethyl ether, tetrahydrofuran, methyl tert-butyl ether, methyltetrahydrofuran, butyl ether and ethylene glycol dimethyl ether.

[0021] Compared with the prior art, the technical solution of the present invention has at least the following beneficial effects:

[0022] 1) 4,4'-biphenyldicarboxylic acid is used as a raw material to prepare a disalt first, and then a mixture of ruthenium alumina and platinum alumina is used as a catalyst to catalytically hydrogenate the benzene ring into cyclohexyl, thereby greatly increasing the trans content of cyclohexyl. The process is simple to operate and has a high trans conversion rate. Moreover, 4,4'-biphenyldicarboxylic acid is relatively cheap and easy to obtain, and has a stable source, so the cost is controllable.

[0023] 2) Carboxyl reduction using a lithium aluminum hydride aluminum chloride complex or a mixture of sodium borohydride and anhydrous zinc chloride can further increase the cyclohexyl trans content to 98% compared to direct lithium aluminum hydride reduction.

[0024] 3) Prepare high purity monosulfonate by controlling the ratio of sulfonyl chloride to diol.

[0025] 4) The route designed by the present invention is unique, and green and environmentally friendly materials and technical routes are used. The process route is short, the process conditions are reasonable, the treatment method is appropriate, the product quality is excellent, the total yield can reach more than 75%, and the post-treatment is relatively simple. No isomerization is required, and more than 98% of the trans product can be obtained. DETAILED DESCRIPTION

[0026] 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.

[0027] The synthesis method of the present invention uses cheap and readily available 4,4'-biphenyldicarboxylic acid as a main raw material, and the synthesis route is as follows:

[0028]

[0029] In the first step, 4,4'-biphenyldicarboxylic acid is used as a raw material, reacted with a base to form a salt, and then subjected to catalytic hydrogenation treatment and acidification to obtain trans, trans-4,4'-bicyclohexyldicarboxylic acid, namely compound 1A.

[0030] According to the literature, 4,4'-biphenyl dicarboxylic acid directly catalytically hydrogenates the benzene ring to easily form cis-trans cyclohexane. The present invention innovatively uses a mixture of ruthenium alumina and platinum alumina as a catalyst for catalytic hydrogenation, and first reacts 4,4'-biphenyl dicarboxylic acid with a base to obtain 4,4'-biphenyl dicarboxylic acid salt, and then catalytically hydrogenates the benzene ring under alkaline conditions, exceeding expectations to obtain more than 95% of the trans product, that is, trans, trans-4,4'-bicyclohexyl dicarboxylic acid (1A).

[0031] In some embodiments, the amount of alkali to 4,4'-biphenyl dicarboxylic acid is (2.1-2.2):1 in a molar ratio, and the alkali is at least one of sodium hydroxide, potassium hydroxide, sodium tert-butoxide and potassium tert-butoxide. The catalyst for catalytic hydrogenation is a mixture of ruthenium alumina and platinum alumina, wherein the ruthenium content in the ruthenium alumina is 3%-10% by mass; the platinum content in the platinum alumina is 1%-5% by mass; the amount of the catalyst to 4,4'-biphenyl dicarboxylic acid is 2%-5% by mass. In the catalyst, the mixing of ruthenium alumina and platinum alumina in any ratio can realize the present invention, for example, the mass ratio of ruthenium alumina: platinum alumina can be any one of 9:1, 7:1, 6:1, 3:1, 1:1, 1:3, 1:5, 1:6, 1:9, etc.

[0032] In some embodiments, a 5%-10% aqueous sodium hydroxide solution is first added to a reaction container, the temperature is controlled below 50°C, 4,4'-biphenyldicarboxylic acid with a mesh size of 150 or more is added in batches, and the mixture is stirred until the system is dissolved and clear, and then the mixture is transferred to a high-pressure container, and 2%-5% ruthenium alumina and platinum alumina are added respectively, and the temperature is 50°C to 80°C, the hydrogenation pressure is 1.0MPa to 3.0MPa, and hydrogen is supplied continuously for 15 hours; hydrogenation is performed to obtain more than 95% trans, trans-4,4'-bicyclohexyl disalt, and the ruthenium alumina and platinum alumina are filtered to remove the ruthenium alumina and platinum alumina, which can be recycled and reused more than three times; the filtrate is adjusted to a pH of 1-2 with dilute acid, and filtered again to obtain a filter cake, the filter cake is washed with water twice, and the temperature is controlled below 95°C and vacuum dried to obtain trans, trans-4,4'-bicyclohexyldicarboxylic acid, with a yield of 95-96%.

[0033] In the second step, in the presence of a reducing agent, trans, trans-4,4'-bicyclohexyl dicarboxylic acid is reduced to trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol to obtain compound 2A.

[0034] The present invention adopts a lithium aluminum hydride aluminum chloride complex or sodium borohydride and anhydrous chlorination reduction process for reducing the carboxyl group, which can further increase the cyclohexyl trans content to 98% of the trans product, i.e., trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol (2A), compared with conventional direct lithium aluminum hydride reduction.

[0035] In some embodiments, the reducing agent is an aluminum chloride complex of lithium aluminum hydride, wherein the amount of the aluminum chloride complex of lithium aluminum hydride to trans, trans-4,4'-bicyclohexyl dicarboxylic acid is (1.8-2.0):1 in a molar ratio.

[0036] Reduction of the aluminum chloride complex of lithium aluminum hydride: first add anhydrous aluminum chloride powder and ether to the reactor, stir for 30 minutes under nitrogen protection, add ether and lithium aluminum hydride to another reaction vessel, heat and reflux and stir until completely dissolved, then cool, press the lithium aluminum hydride ether suspension into the aluminum chloride ether solution, stir for 1 hour after pressing, and obtain the aluminum chloride complex of lithium aluminum hydride. Add 20% trans, trans-4,4'-bicyclohexyl dicarboxylic acid ether solution dropwise to the above lithium aluminum hydride aluminum chloride complex, maintain slow ether reflux, continue to reflux for 3 hours after adding, cool to 10-20°C, first drop water to quench, add 10% sulfuric acid dropwise when hydrogen is no longer generated, stir for 30 minutes to separate, then wash twice with saturated brine, and concentrate the organic layer at normal pressure until no trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol is obtained, with a yield of 95-98%.

[0037] In some embodiments, the reducing agent is a mixture of sodium borohydride and anhydrous zinc chloride, wherein the molar ratio of sodium borohydride to trans, trans-4,4'-bicyclohexyl dicarboxylic acid is (2.2-2.4):1, and the molar ratio of anhydrous zinc chloride to trans, trans-4,4'-bicyclohexyl dicarboxylic acid is (2.2-2.4):1.

[0038] In some embodiments, sodium borohydride and anhydrous zinc chloride reduction: sodium borohydride, zinc chloride and ether are added to a reactor, the temperature is raised to slight reflux, 20% trans, trans-4,4'-bicyclohexyl dicarboxylic acid ether solution is added dropwise, the ether is maintained to slowly reflux, and reflux is continued for 3 hours after the addition is completed, the temperature is lowered to 10°C to 20°C, water is added dropwise to quench, and 10% sulfuric acid is added dropwise when hydrogen is no longer generated, the mixture is stirred for 30 minutes to separate the liquids, and then the mixture is washed twice with saturated brine, and the organic layer is concentrated at normal pressure to obtain trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol with a yield of 95-98%.

[0039] In the third step, trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol reacts with sulfonyl chloride to form trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexyl methanesulfonate, thereby obtaining compound 3.

[0040] The present invention adopts a dripping method and controls the ratio of sulfonyl chloride to achieve monoesterification. As an example, the molar ratio of the sulfonyl chloride to trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol is (1.0-1.05):1, and the sulfonyl chloride is at least one of p-toluenesulfonyl chloride, methanesulfonyl chloride and benzenesulfonyl chloride.

[0041] In some embodiments, the reaction solvent includes a chlorinated solvent, which is less likely to cause side reactions and can keep the reaction system as a homogeneous system. As an example, the chlorinated solvent includes dichloromethane and / or chloroform.

[0042] In some embodiments, an acid-binding agent is added to form a salt from the byproduct hydrochloric acid, which is beneficial to the forward reaction equilibrium and improves the reaction efficiency. The amount of the acid-binding agent and trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol is (1.05-1.1):1 in a molar ratio, wherein the acid-binding agent is at least one of triethylamine, pyridine, diisopropylamine and ethyldiisopropylamine.

[0043] In some embodiments, trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol, triethylamine and dichloromethane are added to the reaction vessel, the temperature is lowered to -20 to -10°C under nitrogen protection, methanesulfonyl chloride is added dropwise at a controlled temperature, the temperature is kept for reaction for 2 hours after the addition is completed, and the temperature is raised to room temperature and stirred for reaction for 6 hours. Water is added dropwise at a temperature below 30°C to quench the reaction, and the organic layer is washed with water twice, the organic layer is concentrated at normal pressure until no product is produced, and then anhydrous methanol is used for crystallization at -20 to -10°C, the crystal product is controlled at a temperature below 50°C, and vacuum dried to obtain trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethyl methanesulfonate with a yield of 90-92%.

[0044] Step 4: Reduction: trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexyl methanesulfonate is reduced with lithium aluminum hydride to obtain trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol, i.e., compound 4A:

[0045] In some embodiments, the amount of lithium aluminum hydride and trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexyl methanesulfonate is calculated in a molar ratio of (1.2-2.0):1, the reaction temperature is -20°C to -10°C, and the reaction solvent is an ether solvent, and the ether solvent is at least one of diethyl ether, tetrahydrofuran, methyl tert-butyl ether, methyltetrahydrofuran, butyl ether and ethylene glycol dimethyl ether.

[0046] In some embodiments, lithium aluminum hydride and tetrahydrofuran are added to the reaction vessel, the temperature is lowered to -20 to -10°C under nitrogen protection, and a 25% tetrahydrofuran solution of trans-4-(trans-4-hydroxymethylcyclohexyl) cyclohexyl methanesulfonate is added dropwise. After the addition is completed, the reaction is kept warm for 2 hours, and the temperature is raised to room temperature and stirred for 4 hours. Water is added dropwise to quench the reaction at a temperature below 30°C, and the organic layer is concentrated under reduced pressure to a temperature below 75°C after separation until no product is produced, and then crystallized with petroleum ether at -25 to -20°C, and the crystals are kept at a temperature below 50°C and dried in vacuo to obtain trans-4-(trans-4-methylcyclohexyl) cyclohexylmethanol with a yield of 95-96%.

[0047] The following is a description of the specific examples. The raw materials or reagents involved in the examples are commercially available unless otherwise specified.

[0048] Example

[0049] The synthetic route is as follows:

[0050]

[0051] Step 1: Synthesis of trans-4,4'-bicyclohexyldicarboxylic acid (1A) (95.08%)

[0052] 336 g (0.84 mol) of 10% aqueous sodium hydroxide solution was added to the reaction flask, the temperature was controlled below 50°C, 96.8 g (0.40 mol) of 4,4'-biphenyldicarboxylic acid with a mesh size of 150 or more was added in batches, and the mixture was stirred until the system was dissolved and clear. The mixture was transferred to a high-pressure container, 2.9 g of 5% ruthenium alumina and 2.5 g of 3% platinum alumina (purchased from Xi'an Kaili New Materials Co., Ltd.) were added, the temperature was controlled at 50°C to 80°C, the hydrogenation pressure was 1.0 MPa, and the hydrogen was supplied for 15 hours while maintaining the temperature and pressure until the reaction stopped absorbing hydrogen. The ruthenium alumina and platinum alumina were filtered off with suction, the filtrate was adjusted to a pH of 1-2 with 176.4 g (0.45 mol) of dilute sulfuric acid, and the filter cake was filtered off again with suction to obtain the filter cake. The filter cake was washed with water twice, and the temperature was controlled below 95°C and vacuum dried to obtain 96.6 g of trans, trans-4,4'-bicyclohexyl dicarboxylic acid (1A), with a yield of 95.08%.

[0053] Step 2: Synthesis of trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol (2A)

[0054] First, add 220g (0.869mol) of anhydrous aluminum chloride powder and 1000ml of ether to a reaction bottle, stir for 30 minutes under nitrogen protection, add 18g (0.474mol) of lithium aluminum hydride and 550ml of ether to another reaction bottle, heat and reflux to stir until completely dissolved, cool, and then press the ether suspension of lithium aluminum hydride into the ether solution of aluminum chloride. Pressing will be completed in about 30 minutes, and stirring will be performed for 1 hour after pressing to obtain an aluminum chloride complex of lithium aluminum hydride (LiAlH4+AlCl3).

[0055] 317.5 g (0.25 mol) of 20% trans, trans-4,4'-bicyclohexyl dicarboxylic acid ether solution was added dropwise to the above-mentioned lithium aluminum hydride aluminum trichloride complex, and the ether was kept slowly refluxed. After the addition was completed, the reflux was continued for 3 hours, and the temperature was lowered to 10°C to 20°C. 100 g of water was first added dropwise to quench, and 200 g of 10% sulfuric acid was added dropwise when no hydrogen was generated. The mixture was stirred for 30 minutes, and the liquids were separated. The organic layer was washed twice with 100 g of saturated brine, and the organic layer was concentrated at normal pressure until no more was produced, to obtain 55.3 g of trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol (2A), with a yield of 97.88%.

[0056] In another embodiment, NaBH4 and ZnCl2 are used as reducing agents to prepare trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol (2A), and the specific steps are as follows:

[0057] To a reaction flask, 8.8 g (0.232 mol) of sodium borohydride, 31.6 g (0.232 mol) of zinc chloride and 250 ml of ether were added, the temperature was raised to slight reflux, 127 g (0.1 mol) of 20% trans, trans-4,4'-dicyclohexyl dicarboxylic acid ether solution was added dropwise, the ether was maintained to slowly reflux, and reflux was continued for 3 hours after the addition was completed. The temperature was lowered to 10-20°C, 40 g of water was added dropwise to quench, and 80 g of 10% sulfuric acid was added dropwise when hydrogen was no longer generated. The mixture was stirred for 30 minutes to separate the liquids, and then washed twice with 40 g of saturated brine. The organic layer was concentrated at normal pressure until no more trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol (2A) was obtained, with a yield of 95.13%.

[0058] Step 3: Synthesis of trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethyl methanesulfonate (3A)

[0059] 45.2g (0.2mol) of trans-4-(trans-4-hydroxymethylcyclohexyl) cyclohexylmethanol, 22.2g (0.22mol) of triethylamine and 200ml of dichloromethane were added to the reaction bottle, and the temperature was lowered to -20℃~-10℃ under nitrogen protection, and 24g of methanesulfonyl chloride (0.21mol) was added dropwise at a temperature control, and the reaction was kept warm for 2 hours after the addition was completed, and the temperature was raised to room temperature and stirred for 6 hours. 50g of water was added dropwise at a temperature control of below 30℃ to quench the reaction, and the organic layer was washed twice with 50g of water, and the organic layer was concentrated at normal pressure until no more was produced, and then 120ml of anhydrous methanol was used for crystallization at -20℃~-10℃, and the crystals were kept at a temperature of below 50℃ and vacuum dried to obtain 54.8g of trans-4-(trans-4-hydroxymethylcyclohexyl) cyclohexyl methyl methanesulfonate (3A), with a yield of 90.13%.

[0060] Step 4: Synthesis of trans-4-(trans-4-propylcyclohexyl)cyclohexylmethanol (4A)

[0061] 5.3 g (0.139 mol) of lithium aluminum hydride and 100 ml of tetrahydrofuran were added to the reaction bottle, cooled to -20°C to -10°C under nitrogen protection, and 121.6 g (0.1 mol) of 25% tetrahydrofuran solution of trans-4-(trans-4-hydroxymethylcyclohexyl) cyclohexyl methyl methanesulfonate was added dropwise. After the addition, the mixture was kept warm for 2 hours, and the mixture was stirred at room temperature for 4 hours. 50 g of water was added dropwise to quench the reaction, and the organic layer was concentrated under reduced pressure to 75°C after separation until no product was produced. 40 ml of petroleum ether was used to crystallize at -25°C to -20°C, and the crystals were kept under 50°C and dried under vacuum to obtain 20 g of trans-4-(trans-4-methylcyclohexyl) cyclohexylmethanol (4A) with a yield of 95.24%.

[0062] In summary, the present invention uses 4,4'-biphenyldicarboxylic acid as a raw material, forms 4,4'-biphenyldicarboxylic acid salt with a base, and then catalytically hydrogenates it, acidifies it to obtain trans, trans-4,4'-bicyclohexyldicarboxylic acid (1A). By optimizing the catalyst, controlling the temperature, and preparing the dicarboxylic acid into a disalt and then catalytically hydrogenating it, the trans content of cyclohexyl is greatly improved, the operation is simple, and the trans conversion rate is high. Furthermore, the aluminum trichloride complex of lithium aluminum hydride or sodium borohydride and anhydrous chlorination are used to reduce the carboxyl group to hydroxymethyl to obtain trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol (2A), which further increases the trans content of cyclohexyl to 98%. Then, trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexyl methanesulfonate (3A) is prepared by controlling the ratio of sulfonyl chloride, and finally the methanesulfonate is reduced with lithium aluminum hydride to obtain trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol (4A), which is purified to obtain the final product. The process conditions of the present invention are reasonable, the product quality and cost are controllable, the total yield can reach more than 75%, and the post-treatment is relatively simple, and no isomerization is required to obtain a trans product with a content of more than 98%.

[0063] 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 trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol, characterized in that: The synthesis method comprises: Step 1, using 4,4'-biphenyldicarboxylic acid as a raw material, reacting with a base to form a salt, and then subjecting to catalytic hydrogenation treatment and acidification to obtain trans, trans-4,4'-bicyclohexyldicarboxylic acid; Step 2, trans, trans-4,4'-bicyclohexyl dicarboxylic acid is reduced to trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol under the action of a reducing agent; Step 3, trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol reacts with sulfonyl chloride to form trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexyl methanesulfonate through monoesterification; Step 4, trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexyl methanesulfonate is reduced with lithium aluminum hydride to obtain trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol.

2. The method for synthesizing trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol according to claim 1, characterized in that: In step 1, the molar ratio of the base to 4,4'-biphenyldicarboxylic acid is (2.1-2.2):1, and the base is at least one of sodium hydroxide, potassium hydroxide, sodium tert-butoxide and potassium tert-butoxide.

3. The method for synthesizing trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol according to claim 1, characterized in that: In step 1, the catalyst for catalytic hydrogenation is a mixture of ruthenium alumina and platinum alumina, wherein the ruthenium content in the ruthenium alumina is 3%-10% by mass, and the platinum content in the platinum alumina is 1%-5% by mass; the amount of the catalyst and 4,4'-biphenyldicarboxylic acid used is 2%-5% by mass.

4. The method for synthesizing trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol according to claim 1, characterized in that: In step 1, the hydrogenation pressure is 1MPa-3MPa, the hydrogenation temperature is 50°C-80°C, and the acidified pH value is 1-2.

5. The method for synthesizing trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol according to claim 1, characterized in that: In step 2, the reducing agent is an aluminum trichloride complex of lithium aluminum hydride, and the amount of the aluminum trichloride complex of lithium aluminum hydride and trans, trans-4,4'-bicyclohexyl dicarboxylic acid used is (1.8-2.0) in a molar ratio of 1:

1.

6. The method for synthesizing trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol according to claim 1, characterized in that: In step 2, the reducing agent is a mixture of sodium borohydride and anhydrous zinc chloride, wherein the molar ratio of sodium borohydride to trans, trans-4,4'-bicyclohexyl dicarboxylic acid is (2.2-2.4):1, and the molar ratio of anhydrous zinc chloride to trans, trans-4,4'-bicyclohexyl dicarboxylic acid is (2.2-2.4):

1.

7. The method for synthesizing trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol according to claim 1, characterized in that: In step 3, the molar ratio of the sulfonyl chloride to trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol is (1.0-1.05):1, and the sulfonyl chloride is at least one of p-toluenesulfonyl chloride, methanesulfonyl chloride and benzenesulfonyl chloride.

8. The method for synthesizing trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol according to claim 1, characterized in that: In step 3, the reaction solvent includes a chlorine-containing solvent, and the chlorine-containing solvent includes dichloromethane and / or chloroform.

9. The method for synthesizing trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol according to claim 1, characterized in that: In step 3, an acid binding agent is also added, and the molar ratio of the acid binding agent to trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexylmethanol is (1.05-1.1):1, wherein the acid binding agent is at least one of triethylamine, pyridine, diisopropylamine and ethyldiisopropylamine.

10. The method for synthesizing trans-4-(trans-4-methylcyclohexyl)cyclohexylmethanol according to claim 1, characterized in that: In step 4, the amount of lithium aluminum hydride and trans-4-(trans-4-hydroxymethylcyclohexyl)cyclohexyl methanesulfonate is (1.2-2.0) in a molar ratio of 1:1, the reaction temperature is -20°C to -10°C, and the reaction solvent is an ether solvent, which is at least one of diethyl ether, tetrahydrofuran, methyl tert-butyl ether, methyltetrahydrofuran, butyl ether and ethylene glycol dimethyl ether.

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