Synthesis method of trans, trans-4-alkylbicyclohexyl-4'-pentyl-3(E)ene liquid crystal monomers

Abstract

This invention discloses a method for synthesizing trans,trans-4-alkyldicyclohexyl-4'-pentyl-3(E)ene liquid crystal monomers. The method comprises: Step 1, reacting trans,trans-4-alkyldicyclohexylbromomethane with a 3-chloropropenylmagnesium chloride Grignard reagent to obtain trans,trans-4-alkyldicyclohexyl-4'-butene-3(E)-1-chloro; Step 2, coupling trans,trans-4-alkyldicyclohexyl-4'-butene-3(E)-1-chloro with a chloromethane Grignard reagent to obtain the target product trans,trans-4-alkyldicyclohexyl-4'-pentyl-3(E)ene. In this synthesis method, both steps can be completed in a one-pot process, which is simple and achieves a final product yield of 80% or higher, with a target product purity of 99.9% or higher. Moreover, the Grignard reagent used in this invention is inexpensive and readily available. During the preparation of the Grignard reagent, the double bond is less prone to isomerization. Therefore, the purity and yield of the reaction product are significantly improved when using the Grignard reagent of this invention.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology and relates to a synthesis technology for liquid crystal display materials, specifically a method for synthesizing trans,trans-4-alkyldicyclohexyl-4'-pentyl-3(E)ene liquid crystal monomers. Background Technology

[0002] Currently, the preparation of trans,trans-4-alkylbicyclohexyl-4 ’ The main methods for producing pentyl-3(E)ene liquid crystal monomers include:

[0003] Route 1: trans,trans-4-alkylbicyclohexylformyl chloride is first coupled with croton chloride Grignard reagent, followed by reduction to remove the hydroxyl group, yielding the target product (see CN113024335A). The reaction formula is as follows:

[0004]

[0005] Route 2: trans,trans-4-alkyldicyclohexylcarboxylic acid is first reduced to trans,trans-4-alkyldicyclohexylmethanol to prepare the corresponding p-toluenesulfonate, which is then coupled with croton chlorogler's reagent to prepare the target product (see CN113024375A). The reaction formula is as follows:

[0006]

[0007] Route 3 involves preparing trans,trans-4-alkylbicyclohexyl ketone as a starting material via a multi-step reaction to yield trans,trans-4-alkylbicyclohexylpropionaldehyde. This is then reacted with bromoethanephosphonium ylide to undergo a Wittig reaction, producing a mixed cis-trans product with double bonds. Finally, the target product is isomerized using sodium benzenesulfinate (see EP2703472A2). The reaction formula is as follows:

[0008]

[0009] Both Route 1 and Route 2 use croton chloride Grignard reagent to couple with relevant substrates. However, croton chloride is expensive and contains many impurities during the preparation of Grignard reagent, which has a certain impact on product quality.

[0010] The above-mentioned route three is a traditional preparation method, which involves a long process and uses ylide reagents, resulting in higher costs. Summary of the Invention

[0011] The purpose of this invention is to provide a method for synthesizing trans,trans-4-alkyldicyclohexyl-4'-pentyl-3(E)ene liquid crystal monomers, which uses readily available raw materials, has a short synthesis route, and is low in cost.

[0012] To achieve the above objectives, the present invention provides a method for synthesizing trans, trans-4-alkyldicyclohexyl-4'-pentyl-3(E)ene liquid crystal monomers, comprising:

[0013] Step 1: Using trans,trans-4-alkylbicyclohexylbromomethane as a starting material, a substitution reaction is carried out with 3-chloropropenyl magnesium chloride Grignard reagent to obtain trans,trans-4-alkylbicyclohexyl-4'-butene-3(E)-1-chloro;

[0014] Step 2: trans, trans-4-alkylbicyclohexyl-4'-butene-3(E)-1-chloro is coupled with chloromethane Grignard reagent to obtain the target product trans, trans-4-alkylbicyclohexyl-4'-pentyl-3(E)ene.

[0015] The reaction equation is:

[0016]

[0017] Wherein, R represents a C1-C5 alkyl straight-chain alkane group.

[0018] Optionally, the 3-chloropropene-based magnesium chloride Grignard reagent is prepared by reacting magnesium with 1,3-dichloropropene in the presence of an initiator.

[0019] Optionally, the molar ratio of magnesium to 1,3-dichloropropylene is 1 to 1.2:1.

[0020] Optionally, in step 1, the molar ratio of 3-chloropropenyl magnesium chloride Grignard reagent to trans,trans-4-alkyldicyclohexyl bromide is 1 to 3:1.

[0021] Optionally, in step 2, the amount of chloromethane Grignard reagent and trans, trans-4-alkylbicyclohexyl-4'-butene-3(E)-1-chloro used is in a molar ratio of 1 to 3:1.

[0022] Optionally, in step 2, a catalyst is also added, wherein the catalyst is iron acetylacetonate.

[0023] Optionally, the amount of the catalyst and the trans, trans-4-alkylbicyclohexyl-4'-butene-3(E)-1-chloro is 0.5% to 3% in molar ratio.

[0024] Optionally, ether-based organic solvents are used in both steps 1 and 2.

[0025] Optionally, the ether organic solvent comprises tetrahydrofuran or 2-methyltetrahydrofuran.

[0026] Compared with the prior art, the present invention has at least the following beneficial effects:

[0027] This invention uses trans,trans-4-alkylbicyclohexylbromomethane as a starting material, which undergoes a substitution reaction with a slightly excess of 3-chloropropenyl magnesium chloride Grignard reagent to prepare trans,trans-4-alkylbicyclohexyl-4'-butene-3(E)-1-chloro. Without further processing, the target product is obtained by direct coupling with a chloromethane Grignard reagent. In the synthesis method of this invention, both steps can be completed in a one-pot process, which is simple and achieves a final product yield of 80% or higher, with a target product purity of 99.9% or higher.

[0028] Furthermore, the Grignard reagent used in this invention is made from inexpensive and readily available raw materials, and the double bonds are less prone to isomerization during the preparation of the Grignard reagent. Therefore, using the Grignard reagent of this invention significantly improves both the purity and yield of the reaction product. Detailed Implementation

[0029] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0030] This invention provides a method for synthesizing a trans, trans-4-alkyldicyclohexyl-4'-pentyl-3(E)ene liquid crystal monomer, the reaction equation of which is:

[0031]

[0032] Where R represents a C1-C5 alkyl group, and for example, it can be methyl, ethyl, n-propyl, n-butyl, etc.

[0033] The method of the present invention includes the following steps:

[0034] Step 1: Using trans,trans-4-alkylbicyclohexylbromomethane as a raw material, a substitution reaction is carried out with 3-chloropropenyl magnesium chloride Grignard reagent to obtain trans,trans-4-alkylbicyclohexyl-4'-butene-3(E)-1-chloro.

[0035] The 3-chloropropene-based magnesium chloride Grignard reagent is prepared by reacting magnesium with 1,3-dichloropropene in the presence of an initiator. Compared to croton chloride, trans-1,3-dichloropropene is much cheaper. Furthermore, during the preparation of croton chloride Grignard reagent, the double bonds are prone to isomerization, which affects the purity and yield of the final product. The trans-1,3-dichloropropene used in this invention avoids this isomerization problem.

[0036] During the preparation of Grignard reagent, magnesium is used in slight excess, and the molar ratio of magnesium to 1,3-dichloropropene is 1 to 1.2:1.

[0037] The molar ratio of 3-chloropropenyl magnesium chloride Grignard reagent to trans,trans-4-alkyldicyclohexyl bromide is 1 to 3:1.

[0038] Step 2: trans, trans-4-alkylbicyclohexyl-4'-butene-3(E)-1-chloro is coupled with chloromethane Grignard reagent to obtain the target product trans, trans-4-alkylbicyclohexyl-4'-pentyl-3(E)ene.

[0039] The molar ratio of chloromethane Grignard reagent to trans,trans-4-alkylbicyclohexyl-4'-butene-3(E)-1-chloro is 1 to 3:1.

[0040] In step 2, a catalyst, namely acetylacetone, was also added. The amount of the catalyst and trans,trans-4-alkylbicyclohexyl-4'-butene-3(E)-1-chloro was 0.5% to 3% in molar ratio.

[0041] Both steps 1 and 2 use ether-based organic solvents. As an example, the ether-based organic solvent may contain tetrahydrofuran or 2-methyltetrahydrofuran.

[0042] The raw materials and reagents used in the following embodiments of the present invention are all commercially available.

[0043] Example 1: Synthesis of trans,trans-4-propylbicyclohexyl-4 ’ -pentyl-3(E)ene

[0044] The reaction equation is as follows:

[0045]

[0046] Add 25.2g of magnesium and 150ml of 2-methyltetrahydrofuran to a 3L three-necked flask. Under inert gas protection, cool the system to 0-5℃. After initiation, add the remaining prepared 1,3-dichloropropene 2-methyltetrahydrofuran solution (111g of 1,3-dichloropropene dissolved in 300ml of 2-methyltetrahydrofuran). After the addition is complete, keep the temperature and stir until the reaction is complete to obtain the 3-chloropropene-based magnesium chloride Grignard reagent system.

[0047] The temperature was controlled at 10-20℃. A 2-methyltetrahydrofuran solution of trans,trans-4-propylbicyclohexylbromomethane (200g of trans,trans-4-propylbicyclohexylbromomethane dissolved in 400ml of 2-methyltetrahydrofuran) was added dropwise to the Grignard reagent system. After the addition was complete, the mixture was kept at a controlled temperature and stirred until it reached the intermediate control level, yielding the intermediate product trans,trans-4-propylbicyclohexyl-4'-butene-3(E)-1-chloro. "Intermediate control level" as used herein refers to the residual raw material reaching a certain level, such as less than 0.1%, detected by the common GC method.

[0048] The temperature was controlled at 0-10℃. 35g of diisopropylamine was added dropwise to the mixed solution system of the intermediate product. After the addition was complete, the mixture was kept at this temperature and stirred for 30 minutes to obtain system A1. The role of diisopropylamine is to destroy excess 1,3-dichloropropene Grignard reagent (3-chloropropene-magnesium chloride Grignard reagent) and prevent subsequent side reactions.

[0049] Under controlled temperature of -5 to -5℃, 4.7g of ferric acetylacetone was added to system A1 as a catalyst, followed by dropwise addition of 300ml of a 2.5mol / L chloromethane Grignard reagent solution of 2-methyltetrahydrofuran. After the reaction was complete, the reaction solution was poured into 600ml of 10% hydrochloric acid for acid hydrolysis. The organic phase was then washed until neutral, concentrated, and the solid was dissolved in 1L of heptane. Column adsorption was performed using 40g of alumina, followed by concentration. 200g of the solid was added to a toluene / ethanol mixed solvent (volume ratio 1:3) and crystallized twice. The crystals were dried to obtain the target product trans, trans-4-propylbicyclohexyl-4-propyltricyclohexyl ... ’ 150g of 1-pentyl-3(E)ene, yield approximately 81.5%, GC content >99.9%.

[0050] Example 2: Synthesis of trans,trans-4-ethylbicyclohexyl-4'-pentyl-3(E)ene

[0051] The reaction equation is shown below:

[0052]

[0053] Add 25.2g of magnesium and 150ml of 2-methyltetrahydrofuran to a 3L three-necked flask. Under inert gas protection, cool the system to 0-5℃. After initiation, add the remaining prepared 1,3-dichloropropene-2-methyltetrahydrofuran solution (111g of 1,3-dichloropropene dissolved in 300ml of 2-methyltetrahydrofuran). After the addition is complete, keep the temperature and stir until the reaction is complete to obtain the 3-chloropropene-based magnesium chloride Grignard reagent system.

[0054] A 2-methyltetrahydrofuran solution of trans, trans-4-ethylbicyclohexylbromomethane (190g trans, trans-4-ethylbicyclohexylbromomethane dissolved in 400ml 2-methyltetrahydrofuran) was added dropwise to the Grignard reagent system at a controlled temperature of 10-20℃. After the addition was complete, the mixture was kept warm and stirred until it met the control temperature, yielding the intermediate product trans, trans-4-ethylbicyclohexyl-4'-butene-3(E)-1-chloro.

[0055] Controlling the temperature at 0-10℃, 35g of diisopropylamine was added dropwise to the mixed solution system of the intermediate product. After the addition was complete, the mixture was kept warm and stirred for 30 minutes to obtain system A2.

[0056] At a controlled temperature of -5 to -5℃, 4.7g of acetylacetone iron was added to system A2, followed by the dropwise addition of 300ml of 2.5mol / L chloromethane Grignard reagent solution of 2-methyltetrahydrofuran. After the reaction was completed, the system was poured into 600ml of 10% hydrochloric acid for acid hydrolysis. The organic phase was washed until neutral, and the concentrated solid was dissolved in 1L of heptane. Column adsorption was performed using 40g of alumina, and the solid was concentrated. 180g of the solid was added to toluene-ethanol (1:4) for crystallization twice. The crystals were dried to obtain 141g of the target compound trans, trans-4-ethylbicyclohexyl-4'-pentyl-3(E)ene, with a yield of approximately 81% and a GC content >99.9%.

[0057] Example 3: Synthesis of trans,trans-4-butyldicyclohexyl-4 ’ -pentyl-3(E)ene

[0058] The reaction equation is as follows:

[0059]

[0060] Add 25.2g of magnesium and 200ml of 2-methyltetrahydrofuran to a 3L three-necked flask. Under inert gas protection, cool the system to 0-5℃. After initiation, add the remaining prepared 1,3-dichloropropene 2-methyltetrahydrofuran solution (111g of 1,3-dichloropropene dissolved in 300ml of 2-methyltetrahydrofuran). After the addition is complete, keep the system warm and stir until the reaction is complete to obtain the 3-chloropropene-based magnesium chloride Grignard reagent system.

[0061] A 2-methyltetrahydrofuran solution of trans, trans-4-butylbicyclohexylbromomethane (209 g of trans, trans-4-butylbicyclohexylbromomethane dissolved in 400 ml of 2-methyltetrahydrofuran) was added dropwise to the Grignard reagent system at a controlled temperature of 10-20℃. After the addition was complete, the mixture was kept warm and stirred until it met the control temperature, yielding the intermediate product trans-4-butylbicyclohexyl-4'-butene-3(E)-1-chloro.

[0062] Controlling the temperature at 0-10℃, 35g of diisopropylamine was added dropwise to the mixed solution system of the intermediate product. After the addition was complete, the mixture was kept warm and stirred for 30 minutes to obtain system A3.

[0063] Under controlled temperature of -5 to -5℃, 4.7g of acetylacetone iron was added to system A3, followed by dropwise addition of 300ml of chloromethane Grignard reagent in 2-methyltetrahydrofuran solution (2.5mol / L). After the reaction was complete, the reaction solution was poured into 600ml of dilute hydrochloric acid (10%) for acid hydrolysis. The organic phase was washed until neutral, concentrated, and the solid was dissolved in 1L of heptane. Column adsorption was performed using 40g of alumina, and the solution was concentrated to obtain 200g of solid product. The solid product was crystallized twice with a toluene / ethanol mixed solvent (volume ratio 1:3). The crystals were dried to obtain 155g of the target compound trans, trans-4-butyldicyclohexyl-4'-pentyl-3(E)ene, with a yield of approximately 80% and a GC content >99.9%.

[0064] In summary, this invention uses trans,trans-4-alkylbicyclohexylbromomethane as a starting material and reacts it with a 3-chloropropenyl magnesium chloride Grignard reagent to obtain trans,trans-4-alkylbicyclohexyl-4'-buten-3(E)-1-chloro; then, it is coupled with a chloromethane Grignard reagent to obtain the target product trans,trans-4-alkylbicyclohexyl-4'-pentyl-3(E)ene. Both steps are completed in a one-pot process, which is simple and achieves a final product yield of 80% or higher, with a target product purity of over 99.9%. Furthermore, the Grignard reagent used in this invention is inexpensive and readily available. During the preparation of the Grignard reagent, the double bond is less prone to isomerization. Therefore, using the Grignard reagent of this invention significantly improves both the purity and yield of the reaction product.

[0065] Although the present invention has been described in detail through the preferred embodiments above, it should be understood that the above description should not be considered as a limitation of the present invention. Various modifications and substitutions to the present invention will be apparent to those skilled in the art after reading the above description. Therefore, the scope of protection of the present invention should be defined by the appended claims.

Claims

1. A method for synthesizing a trans, trans-4-alkyldicyclohexyl-4'-pentyl-3(E)ene liquid crystal monomer, characterized in that, The method includes: Step 1: Using trans,trans-4-alkylbicyclohexylbromomethane as a starting material, a substitution reaction is carried out with 3-chloropropenyl magnesium chloride Grignard reagent to obtain trans,trans-4-alkylbicyclohexyl-4'-butene-3(E)-1-chloro; Step 2: trans, trans-4-alkylbicyclohexyl-4'-butene-3(E)-1-chloro is coupled with chloromethane Grignard reagent under the action of a catalyst to obtain the target product trans, trans-4-alkylbicyclohexyl-4'-pentyl-3(E)ene. The catalyst is iron acetylacetone. The reaction equation is: Where R represents a C1-C5 straight-chain alkane group.

2. The method for synthesizing trans, trans-4-alkyldicyclohexyl-4'-pentyl-3(E)ene liquid crystal monomers as described in claim 1, characterized in that, The 3-chloropropene-based magnesium chloride Grignard reagent is prepared by reacting magnesium with 1,3-dichloropropene in the presence of an initiator.

3. The method for synthesizing the trans, trans-4-alkyldicyclohexyl-4'-pentyl-3(E)ene liquid crystal monomer as described in claim 2, characterized in that, The molar ratio of magnesium to 1,3-dichloropropene is 1~1.2:

1.

4. The method for synthesizing the trans, trans-4-alkyldicyclohexyl-4'-pentyl-3(E)ene liquid crystal monomer as described in claim 1, characterized in that, In step 1, the molar ratio of 3-chloropropenyl magnesium chloride Grignard reagent to trans,trans-4-alkyldicyclohexyl bromide is 1~3:

1.

5. The method for synthesizing trans, trans-4-alkyldicyclohexyl-4'-pentyl-3(E)ene liquid crystal monomers as described in claim 1, characterized in that, In step 2, the amounts of chloromethane Grignard reagent and trans, trans-4-alkylbicyclohexyl-4'-butene-3(E)-1-chloro are used in a molar ratio of 1 to 3:

1.

6. The method for synthesizing the trans, trans-4-alkyldicyclohexyl-4'-pentyl-3(E)ene liquid crystal monomer as described in claim 1, characterized in that, The amount of the catalyst and the trans, trans-4-alkylbicyclohexyl-4'-butene-3(E)-1-chloro is 0.5% to 3% in molar ratio.

7. The method for synthesizing the trans, trans-4-alkyldicyclohexyl-4'-pentyl-3(E)ene liquid crystal monomer as described in claim 1, characterized in that, Both steps 1 and 2 use ether-based organic solvents.

8. The method for synthesizing the trans, trans-4-alkyldicyclohexyl-4'-pentyl-3(E)ene liquid crystal monomer as described in claim 7, characterized in that, The ether-based organic solvents include tetrahydrofuran and / or 2-methyltetrahydrofuran.

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