Preparation method of 4, 6-difluorodibenzothiophene liquid crystal monomer

Abstract

The invention provides a preparation method of a 4, 6-difluorodibenzothiophene liquid crystal monomer, which comprises the following steps of: a, preparing a compound III by taking alkoxy phenylboronic acid as a raw material through Suzuki coupling reaction; b, carrying out esterification reaction on the compound III and trifluoromethanesulfonic anhydride to prepare a compound IV; step c, carrying out substitution reaction on the compound IV and ethyl thiohydracrylate to prepare a compound V; and step d, carrying out ring closing on the compound V to prepare a compound VI, namely the 4, 6-difluorodibenzothiophene liquid crystal monomer. According to the preparation method, the process route is shortened, and the safety is improved. The method overcomes the property defects of long reaction route, difficulty in purification, low yield, poor safety and unsuitability for large-scale production of tetrahydropyran liquid crystal compounds prepared by the original route.

Description

Technical Field

[0001] The invention belongs to the technical field of liquid crystals and relates to a liquid crystal monomer, and in particular to a method for preparing a 4,6-difluorodibenzothiophene liquid crystal monomer. Background Art

[0002] Currently, the mainstream full-color LCD screens on the market all use thin-film transistors (TFT) to drive the liquid crystal molecules to open or close under the action of an electric field, modulating the light to achieve display purposes. Technically speaking, TFT liquid crystal technology can be divided into three display modes: twisted nematic (TN), in-plane switching (IPS, and fringe field switching (FFS) which is a further upgrade of IPS), and vertical alignment (VA), according to the different arrangement of liquid crystal molecules. All of these modes have been widely used.

[0003] The negative liquid crystal material used in VA-TFT technology has the advantages of large visible light and fast response speed. The use of negative liquid crystal material can not only greatly improve the transmittance of the device, improve the contrast and resolution of the display, but also perform better in color deviation and under the influence of vertical electric field.

[0004] As VA and FFS become the mainstream in liquid crystal display modes, the demand for negative liquid crystal materials continues to increase, and the synthesis research of new structure liquid crystal monomers has become an important task in the field of liquid crystal synthesis.

[0005] The Chinese invention patent with application publication number CN 105153112 A provides a method for synthesizing a target product, which requires seven steps to obtain the target product, has a low yield, and is poor in economic efficiency. The Chinese invention patent with application publication number CN 109423297A provides a synthesis method, which requires the use of tert-butyl lithium and has poor safety. Summary of the invention

[0006] In view of the shortcomings of the prior art, the purpose of the present invention is to provide a method for preparing 4,6-difluorodibenzothiophene liquid crystal monomers to solve the technical problem that the method for preparing tetrakis 4,6-difluorodibenzothiophene liquid crystal monomers in the prior art is difficult to take into account both short process route and safety.

[0007] In order to solve the above technical problems, the present invention adopts the following technical solutions to achieve the above problems:

[0008] A method for preparing 4,6-difluorodibenzothiophene liquid crystal monomer, the method is carried out according to the following steps:

[0009] Step a, using alkoxyphenylboronic acid as a raw material, preparing compound III through Suzuki coupling reaction.

[0010] Step b, compound III is subjected to esterification reaction with trifluoromethanesulfonic anhydride to prepare compound IV.

[0011] Step c, compound IV is subjected to substitution reaction with ethyl mercaptopropionate to prepare compound V.

[0012] Step d: Compound V is subjected to ring closure to obtain compound VI, wherein the compound VI is a 4,6-difluorodibenzothiophene liquid crystal monomer.

[0013] The structural formula of the alkoxyphenylboronic acid is:

[0014] The structural formula of the compound III is:

[0015] The structural formula of the compound IV is:

[0016] The structural formula of the compound V is:

[0017] The structural formula of the compound VI is:

[0018] Where:

[0019] R1=C1~C7 alkyl, C1~C7 alkyl, -CF3, -OCF3, -OCHF2 or -OCH2F.

[0020] R2=C1~C7 alkyl, C1~C7 alkyl, -CF3, -OCF3, -OCHF2 or -OCH2F.

[0021] The present invention also has the following technical features:

[0022] In step a, a first catalyst is used, and the first catalyst is Pd(amphos)Cl2.

[0023] In step b, a second catalyst is used, and the second catalyst is triethylamine.

[0024] In step c, a third catalyst is used, and the third catalyst is Pd(dba)2.

[0025] Specifically, the method is carried out according to the following steps:

[0026] Step a, under nitrogen protection, compound I, compound II, base, water, a first catalyst and a first solvent are mixed, heated to reflux for 2h to 4h, the reaction is completed, and the first solvent is added, stirred, allowed to stand, separated, and then extracted, washed, dried, filtered, concentrated and purified to obtain compound III.

[0027] The structural formula of the compound II is:

[0028] Step b, under nitrogen protection, dissolving the obtained compound III in a second solvent, adding a second catalyst at a temperature of 10-20° C., adding trifluoromethanesulfonic anhydride at a temperature of 10-20° C., reacting at a temperature of 10-20° C., and keeping warm for 2 hours after the addition is completed. After the reaction is completed, adding the second solvent again, stirring, standing, separating the liquids, and then extracting, washing, drying, filtering, concentrating and purifying to obtain compound IV.

[0029] Step c, under nitrogen protection, dissolving the obtained compound IV in a third solvent, adding ethyl mercaptopropionate and diisopropylamine as an acid binder, heating under reflux for 24 hours under the condition of a third catalyst, and cooling to after the reaction to obtain compound V.

[0030] Step d, dissolving potassium tert-butoxide in tetrahydrofuran, and dropping the solution into the reaction solution of step c. After the addition is complete, reflux for 8 hours, cool the reaction mixture to room temperature, let it stand, separate the liquids, extract, wash, dry, filter, concentrate and purify to obtain compound VI.

[0031] Preferably, in step a, the first solvent is toluene; in step b, the second solvent is dichloromethane; in step c, the third solvent is toluene.

[0032] Compared with the prior art, the present invention has the following technical effects:

[0033] (I) The preparation method of the present invention shortens the process route and improves safety, thereby overcoming the defects of the original route for preparing tetrahydropyran liquid crystal compounds, such as long reaction route, difficulty in purification, low yield, poor safety, and unsuitability for large-scale production.

[0034] (II) Compared with Beijing Bayi Shikong (CN 109423297A), the present invention avoids the use of organic lithium and improves the safety of the reaction. Compared with Merck (CN 105153112A), the synthetic route to obtain the target product is simplified.

[0035] (III) The present invention utilizes alkoxy fluorine phenylboronic acid and alkoxy fluorine bromobenzene to prepare compound III through Suzuki coupling reaction under the catalysis of Pd(amphos)Cl2, which can effectively control the self-coupling of alkoxy fluorine phenylboronic acid and improve the yield.

[0036] (IV) The intermediate produced by the preparation method of the present invention is easy to post-process and purify, and easy to store, which solves the technical problems in the prior art of preparing tetrakis 4,6-difluorodibenzothiophene liquid crystal monomers that the intermediate is active and difficult to post-process and purify and difficult to store.

[0037] (V) The raw materials of the present invention are easily available, the reaction yield is improved, the equipment requirements are low, and it is suitable for large-scale production.

[0038] The specific contents of the present invention are further described in detail below in conjunction with embodiments. DETAILED DESCRIPTION

[0039] It should be noted that, unless otherwise specified, all raw materials in the present invention are raw materials known in the prior art.

[0040] In the present invention, Pd(amphos)Cl2 refers to bis(di-tert-butyl-(4-dimethylaminophenyl)phosphine)palladium dichloride; Pd(dba)2 refers to bis(dibenzylideneacetone)palladium. Both Pd(amphos)Cl2 and Pd(dba)2 are known commercially available products.

[0041] The structural formula of the 4,6-difluorodibenzothiophene liquid crystal monomer of the present invention is:

[0042]

[0043] Where:

[0044] R1=C1~C7 alkyl, C1~C7 alkyl, -CF3, -OCF3, -OCHF2 or -OCH2F.

[0045] R2=C1~C7 alkyl, C1~C7 alkyl, -CF3, -OCF3, -OCHF2 or -OCH2F.

[0046] 4,6-Difluorodibenzothiophene liquid crystal monomer is prepared according to the following reaction formula:

[0047]

[0048] The 4,6-difluorodibenzothiophene liquid crystal monomer of the present invention is used as a negative liquid crystal material.

[0049] In accordance with the above technical scheme, specific embodiments of the present invention are given below. It should be noted that the present invention is not limited to the following specific embodiments, and all equivalent changes made on the basis of the technical scheme of this application fall within the protection scope of the present invention.

[0050] Embodiment 1:

[0051] This embodiment provides a method for preparing a 4,6-difluorodibenzothiophene liquid crystal monomer, which is carried out according to the following steps:

[0052] Step a, synthesis of 4-butoxy-4'-ethoxy-2',3,3'-trifluoro(1,1'-biphenyl)-2-phenol:

[0053]

[0054] Under nitrogen protection, 100 ml of deionized water was added to a 500 ml three-necked flask, stirring was started, 31.52 g (228.05 nmol) of potassium carbonate was added, and the mixture was stirred to dissolve. 200 ml of toluene was added, 18.42 g (91.22 nmol) of compound I and 20 g (76.01 nmol) of compound II were added and stirred thoroughly. 0.1 g of Pd (amphos) Cl2 was added, heating was started, the temperature was raised to reflux, and the reaction was kept warm for 2 h, then the temperature was lowered to room temperature, and dilute hydrochloric acid was slowly added to the reaction solution to quench the reaction. Toluene was then added, stirred, allowed to stand, and the liquids were separated. The organic phases were extracted and combined, dried and concentrated, and recrystallized from ethanol to obtain 24.8 g (72.87 nmol) of white crystals, which was compound III (yield = 95.86%).

[0055] Step b, synthesis of 4-butoxy-4'-ethoxy-2',3,3'-trifluoro(1,1'-biphenyl)-2-trifluoromethanesulfonic acid phenol ester:

[0056]

[0057] Under nitrogen protection, 200 ml of dichloromethane was added to a 500 ml three-necked flask, stirring was started, 24.8 g (72.87 nmol) of compound III was added, and the mixture was stirred to dissolve. At room temperature, 18.43 g (182.17 nmol) of triethylamine was added, and 41.12 g (145.74 nmol) of trifluoromethanesulfonic anhydride was added dropwise with a constant pressure bottom liquid funnel. After the addition was completed, the mixture was kept warm for 2 hours. The reaction solution was slowly added to water to quench the reaction. After the reaction was completed, dichloromethane was added again, stirred, allowed to stand, and the liquids were separated. The organic phases were extracted and combined, dried and concentrated, and recrystallized from ethanol to obtain 32.3 g (68.37 nmol) of white crystals, i.e. compound IV (yield = 93.83%).

[0058] Step c, synthesis of ethyl 3-(4-butoxy-4'-ethoxy-2'-, 3,3'-trifluoro-[1,1'-biphenyl]-)thio)propionate:

[0059]

[0060] Under nitrogen protection, 400 ml of toluene was added to a 1000 ml three-necked flask, stirring was started, 32.3 g (68.37 nmol) of compound IV, 18.35 g (136.75 nmol) of ethyl mercaptopropionate, 20.76 g (205.11 nmol) of diisopropylamine (DIPA), and 3.13 g (3.42 nmol) of Pd(dba)2 were added, heating was started to raise the temperature to 110°C, and the reaction was kept warm for 24 hours. After the reaction was completed, the temperature was lowered to room temperature to obtain compound V.

[0061] Step d, synthesis of 3-ethoxy-7-butoxy-4,6-difluorodibenzothiophene,

[0062]

[0063] Under nitrogen protection, 19.18 g (170.94 nmol) of potassium tert-butoxide was dissolved in 100 ml of tetrahydrofuran. At room temperature, the tetrahydrofuran solution of potassium tert-butoxide was added dropwise to the reaction solution in step c using a constant pressure funnel. The reaction was exothermic. After the addition was complete, the heating was turned on and the temperature was raised to reflux for 8 h. The temperature was lowered to room temperature. Dilute hydrochloric acid was slowly added to the reaction solution for acidolysis. The solution was extracted, washed with water, and dried. After concentrated drying, ethanol was recrystallized to obtain 14.2 g (44 nmol) of white crystalline product, i.e., compound VI, with a gas phase content GC = 99.9% and a yield of 64.35%.

[0064] The white crystalline product of step d is characterized as follows:

[0065] GC-MS (m / z): 336.1 (100.0%).

[0066] IR (KBr, cm -1 ): υC-OC: 1276, 1056; υC-F: 1257, 1247; υ-c=c(benzene

[0067] Ring): 1195, 1147, 1111, 838; υ-CH2-: 2931, 2871; σring: 745, 671, 644.

[0068] 1H NMR (400M, CDCl3): 0.99(t,j=8Hz,3H CH3), 1.47(t,j=8Hz, 3H CH3), 1.48~1.58(m,2H CH2), 1.79~1.86(m,2H CH2) 4.13 (t, j = 8Hz, OCH2), 4.26 (q, j = 8Hz, OCH2) 7.29 (t, j = 8Hz, 2H Ar-H) 7.65 (d, j = 8Hz, 2H Ar-H.

[0069] It can be seen from the above characterization results that the white crystalline product of step d is the target compound 3-ethoxy-7-butoxy-4,6-difluorodibenzothiophene liquid crystal monomer.

[0070] Embodiment 2:

[0071] This embodiment provides a method for preparing a 4,6-difluorodibenzothiophene liquid crystal monomer, which is carried out according to the following steps:

[0072] Step a, Synthesis of 4-butoxy-4'-(2,2,2,-trifluoroethoxy)-2',3,3'-trifluoro(1,1'-biphenyl)-2-phenol

[0073]

[0074] Under nitrogen protection, add 100 ml of deionized water to a 500 ml three-necked flask, start stirring, add 31.52 g (228.05 nmol) of potassium carbonate, stir to dissolve, add 200 ml of toluene, add 20 (76.01 nmol) of compound Ⅰ and 23.35 g (91.22 nmo) of compound Ⅱ and stir well, add 1 g Pd(amphos)Cl2, start heating, raise the temperature to reflux, keep the reaction for 2 hours, then cool to room temperature, slowly add dilute hydrochloric acid to the reaction solution to quench the reaction, then add toluene, stir, let stand, separate the liquids, dry and concentrate, and recrystallize from ethanol to obtain 28.3 g (71.77 nmol) of white crystals, which is compound Ⅲ (yield = 94.42%).

[0075] Step b, synthesis of 4-butoxy-4'-(2,2,2,-trifluoroethoxy)-2',3,3'-trifluoro(1,1'-biphenyl)-2-trifluoromethanesulfonic acid phenol ester:

[0076]

[0077] Under nitrogen protection, 200 ml of dichloromethane was added to a 500 ml three-necked flask, stirring was started, 28.3 g (71.77 nmol) of compound III was added, and the mixture was stirred and dissolved. At room temperature, 18.16 g (179.43 nmol) of triethylamine was added, and 40.5 g (143.54 nmol) of trifluoromethanesulfonic anhydride was added dropwise with a constant pressure bottom liquid funnel. After the addition was completed, the mixture was kept warm for 2 hours. The reaction solution was slowly added to water to quench the reaction. After the reaction was completed, dichloromethane was added again, stirred, allowed to stand, separated, the organic phases were extracted and combined, dried and concentrated, and recrystallized from ethanol to obtain 31.8 g (67.32 nmol) of white crystals, which were compound IV (yield = 93.79%).

[0078] Step c, synthesis of ethyl 3-(4-butoxy-2',3,3'-trifluoro-4'-(2,2,2-trifluoroethoxy)-[1,1'-biphenyl]-2-thio)propanoate:

[0079]

[0080] Under nitrogen protection, 400 ml of toluene was added to a 1000 ml three-necked flask, stirring was started, 31.8 g (67.32 nmol) of compound IV, 16.21 g (134.64 nmol) of ethyl mercaptopropionate, 20.44 g (201.96 nmol) of diisopropylamine (DIPA), and 3.08 g (3.366 nmol) of Pd(dba)2 were added, heating was started to raise the temperature to 110°C, and the reaction was kept warm for 24 hours. After the reaction was completed, the temperature was lowered to room temperature to obtain compound V.

[0081] Step d, synthesis of 3-ethoxy-7-(2,2,2-trifluoroethoxy)-4,6-difluorodibenzothiophene:

[0082]

[0083] Under nitrogen protection, 18.88 g (168.3 nmol) of potassium tert-butoxide was dissolved in 100 ml of tetrahydrofuran. At room temperature, the tetrahydrofuran solution of potassium tert-butoxide was added dropwise to the reaction solution of step c using a constant pressure funnel. The reaction was exothermic. After the addition was complete, the heating was turned on and the temperature was raised to reflux for 8 h. The temperature was lowered to room temperature. Dilute hydrochloric acid was slowly added to the reaction solution for acidolysis. The solution was extracted, washed with water, and dried. After concentrated drying, ethanol was recrystallized to obtain 14.8 g (44 nmol) of white crystalline product, i.e., compound VI, with a gas phase content GC = 99.9% and a yield of 62.76%.

[0084] The white crystalline product of step d is characterized as follows:

[0085] GC-MS (m / z): m / z: 390.07 (100.0%), 391.07 (20.3%), 392.07 (4.7%), 392.08 (2.3%).

[0086] 1H NMR (400M, CDCl3): 0.96 (t, j = 8Hz, 3H CH3), 1.47 (t, j = 8Hz, 2H CH2), 1.74 (m, 2H CH2), 4.06 (t, j = 8Hz, OCH2), 4.46 (q, j = 8Hz, OCH2) 7.11 (t, j = 8Hz, 2H Ar-H)7.82(d,j=8Hz,2H Ar-H).

[0087] It can be seen from the above characterization results that the white crystalline product of step d is the target compound 3-ethoxy-7-(2,2,2-trifluoroethoxy)-4,6-difluorodibenzothiophene liquid crystal monomer.

[0088] Comparative Example 1:

[0089] This comparative example provides a method for preparing a liquid crystal monomer compound, and specifically refers to the Chinese invention patent with application publication number CN105153112A. The method is carried out according to the following reaction route:

[0090]

[0091] Compared with the steps of Examples 1 and 2, the route of this comparative example is longer and is not suitable for large-scale production.

[0092] Comparative Example 2:

[0093] This comparative example provides a method for preparing a liquid crystal monomer compound, and specifically refers to the Chinese invention patent with application publication number CN109423297A. The method is carried out according to the following reaction route:

[0094]

[0095] Comparing the steps of this route with those of Examples 1 and 2, tert-butyl lithium is used in the reaction process. Tert-butyl lithium has high activity and is not suitable for large-scale production. The total yield in Comparative Example 2 is 46.4%.

Claims

1. A method for preparing 4,6-difluorodibenzothiophene liquid crystal monomer, characterized in that: The method proceeds as follows: Step a, using alkoxyphenylboronic acid as a raw material, preparing compound III through Suzuki coupling reaction; Step b, compound III is subjected to esterification reaction with trifluoromethanesulfonic anhydride to prepare compound IV; Step c, compound IV is subjected to substitution reaction with ethyl mercaptopropionate to prepare compound V; Step d, compound V is subjected to ring closure to obtain compound VI, wherein the compound VI is a 4,6-difluorodibenzothiophene liquid crystal monomer; The structural formula of the alkoxyphenylboronic acid is: The structural formula of the compound III is: The structural formula of the compound IV is: The structural formula of the compound V is: The structural formula of the compound VI is: Where: R1=C1~C7 alkyl, C1~C7 alkyl, -CF3, -OCF3, -OCHF2 or -OCH2F; R2=C1~C7 alkyl, C1~C7 alkyl, -CF3, -OCF3, -OCHF2 or -OCH2F.

2. The method for preparing 4,6-difluorodibenzothiophene liquid crystal monomer according to claim 1, characterized in that: In step a, a first catalyst is used, and the first catalyst is Pd(amphos)Cl2.

3. The method for preparing 4,6-difluorodibenzothiophene liquid crystal monomer according to claim 1, characterized in that: In step b, a second catalyst is used, and the second catalyst is triethylamine.

4. The method for preparing 4,6-difluorodibenzothiophene liquid crystal monomer according to claim 1, characterized in that: In step c, a third catalyst is used, and the third catalyst is Pd(dba)2.

5. The method for preparing 4,6-difluorodibenzothiophene liquid crystal monomer according to any one of claims 1 to 4, characterized in that: The method proceeds as follows: Step a, under nitrogen protection, compound I, compound II, base, water, a first catalyst and a first solvent are mixed, heated to reflux for 2h to 4h, the reaction is completed, and the first solvent is added, stirred, allowed to stand, separated, and then extracted, washed, dried, filtered, concentrated and purified to obtain compound III; The structural formula of the compound II is: Step b, under nitrogen protection, dissolving the obtained compound III in a second solvent, adding a second catalyst at a temperature of 10-20° C., adding trifluoromethanesulfonic anhydride dropwise at a temperature of 10-20° C., reacting at a temperature of 10-20° C., and keeping the temperature for 2 hours after the addition is completed. After the reaction is completed, adding the second solvent again, stirring, standing, separating the liquids, and then extracting, washing, drying, filtering, concentrating and purifying to obtain compound IV; Step c, under nitrogen protection, dissolving the obtained compound IV in a third solvent, adding ethyl mercaptopropionate and diisopropylamine as an acid-binding agent, heating under reflux for 24 hours under the condition of a third catalyst, and cooling to a temperature after the reaction to obtain compound V; Step d, dissolving potassium tert-butoxide in tetrahydrofuran, and dropping the solution into the reaction solution of step c. After the addition is complete, reflux for 8 hours, cool the reaction mixture to room temperature, let it stand, separate the liquids, extract, wash, dry, filter, concentrate and purify to obtain compound VI.

6. The method for preparing 4,6-difluorodibenzothiophene liquid crystal monomer according to claim 5, characterized in that: In step a, the first solvent is toluene; in step b, the second solvent is dichloromethane; in step c, the third solvent is toluene.

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