CN111704912A - Novel preparation method of 3-alkenyl benzyne liquid crystal compound - Google Patents

Novel preparation method of 3-alkenyl benzyne liquid crystal compound Download PDF

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CN111704912A
CN111704912A CN202010605590.6A CN202010605590A CN111704912A CN 111704912 A CN111704912 A CN 111704912A CN 202010605590 A CN202010605590 A CN 202010605590A CN 111704912 A CN111704912 A CN 111704912A
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王艳伟
衣志伟
姜晓辉
王谦
国新涛
丰佩川
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Yantai Fengpeng Lcd Material Co ltd
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Abstract

The invention relates to a novel preparation method of a 3-alkenyl benzyne liquid crystal compound, which comprises the following steps: taking phenylpropionic acid as a raw material, and preparing an intermediate I-1 through halogenation; the intermediate I-1 and alcohol are subjected to esterification reaction under the catalysis of acid or acyl chloride to prepare an intermediate I-2; reacting the intermediate I-2 with an ethynylation reagent under an alkaline condition and in the presence of a transition metal catalyst to obtain I-3; i-3, preparing I-4 under the reduction of borohydride; i-4 is selectively oxidized under the action of an oxidant to prepare I-5; i-5, preparing the 3-alkenyl benzyne liquid crystal compound through wittig reaction. The new preparation method can avoid the generation of byproducts in the synthesis process, has high synthesis efficiency, high product quality and low cost, has simple and easy post-treatment method, is beneficial to industrialized mass production, and is completely suitable for the requirements of high quality and high quality of liquid crystal materials at present.

Description

Novel preparation method of 3-alkenyl benzyne liquid crystal compound
Technical Field
The invention relates to a novel preparation method of a 3-alkenyl benzyne liquid crystal compound, belonging to the technical field of liquid crystal compounds.
Background
Liquid crystal displays have been widely used in various aspects of social life, and liquid crystal display technologies have been developed so far, and various liquid crystal compounds have been put to practical use. Some common requirements for liquid crystal compounds, including phase transition temperature, optical anisotropy, dielectric anisotropy, viscosity, etc., of the liquid crystal compounds, have a great influence on the final application of the liquid crystal material.
The 3-alkenyl phenylacetylene liquid crystal compound can be widely applied to STN-LCD, and the liquid crystal has high birefringence, wider nematic phase transition temperature, lower viscosity, lower intersolubility, larger K33/K11 value and good steepness, and is a liquid crystal compound with excellent performance. Therefore, the preparation of the high-quality 3-alkenyl phenylacetylene liquid crystal compound has very important value.
In patent JPA 1998017500, a synthetic method using p-bromobenzyl bromide as a raw material is disclosed as the following scheme 1:
Figure BDA0002558859050000011
when the circuit is used for preparing allyl magnesium bromide, the temperature needs to be strictly controlled, otherwise, a large amount of self-coupling products exist, and the final step of reaction is carried out, when bis- (triphenylphosphine) palladium dichloride is used as a catalyst for Sonogashira cross coupling, a serious Heck side reaction exists, partial terminal alkene participates in the reaction, and the product quality is poor.
In patent JP2001294541, a synthetic method of the 3-alkenyl phenylacetylene liquid crystal compound is disclosed by taking methyl iodobenzoate as a raw material, and the compound is obtained by the following reaction process of scheme 2:
Figure BDA0002558859050000021
the synthetic route of scheme 2 is a great improvement, but during the research, the synthetic route is found to have the following two defects: (1) preparation of ethyl p-iodobenzoate as raw material
Figure BDA0002558859050000022
In the process, because of the existence of CuI, Glaser side reaction occurs to generate 2-10% of 1, 3-diyne impurities, which are very difficult to purify and influence the product quality and the effective utilization rate of raw materials; (2) finally, the Grignard coupling reaction has a small amount of terminal olefinic double bond migration phenomenon, and can also cause great challenges to the purification of products.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a novel preparation method of a 3-alkenyl benzyne liquid crystal compound, which has the advantages of easily available raw materials, low price, reasonable route and high product quality.
The technical scheme for solving the technical problems is as follows: a novel preparation method of a 3-alkenyl benzyne liquid crystal compound comprises the following process flows:
Figure BDA0002558859050000023
Figure BDA0002558859050000031
wherein R is1Is an alkyl group having 1 to 7 carbon atoms; r2An alkyl group having 1 to 5 carbon atoms; x is halogen, and the halogen is chlorine, bromine or iodine;
a novel preparation method of a 3-alkenyl benzyne liquid crystal compound comprises the following steps:
1) taking phenylpropionic acid as a raw material, and preparing an intermediate I-1 through halogenation;
Figure BDA0002558859050000032
2) the intermediate I-1 and alcohol are subjected to esterification reaction under the catalysis of acid or acyl chloride to prepare an intermediate I-2;
Figure BDA0002558859050000033
3) carrying out Sonogashira cross-coupling reaction on the intermediate I-2 and an ethynylation reagent under an alkaline condition and in the presence of a transition metal catalyst to obtain I-3;
Figure BDA0002558859050000034
4) i-3, preparing I-4 under the reduction of borohydride;
Figure BDA0002558859050000035
5) i-4 is selectively oxidized under the action of an oxidant to prepare I-5;
Figure BDA0002558859050000036
6) i-5 and a wittig reagent prepared from bromomethane triphenylphosphine salt and alkali are subjected to wittig reaction to prepare the 3-alkenyl phenylalkyne liquid crystal compound I;
Figure BDA0002558859050000037
wherein R is1Is an alkyl group having 1 to 7 carbon atoms; r2An alkyl group having 1 to 5 carbon atoms; x is halogen, including chlorine, bromine or iodine.
Further, in the step 1), in the halogenation reaction, a chlorination reagent, a bromination reagent or an iodination reagent reacts with the phenylpropionic acid;
in the step 2), the acid is sulfuric acid, phosphoric acid or boron trifluoride diethyl etherate, the acyl chloride is oxalyl chloride or thionyl chloride, and the alcohol is saturated fatty alcohol;
in the step 3), the transition metal catalyst is Pd (PPh)3)Cl2、Pd(OAc)21, 1' -bis (diphenylphosphino) ferrocene dichloropalladium (II), Pd (dba)3Or one or a plurality of bis (di-tert-butyl- (4-dimethylaminophenyl) phosphine) palladium dichloride (II) in any proportion;
in the step 3), the ethynylation reagent is acetylene gas, calcium carbide or acetylene derivatives; the alkaline condition is one or a mixture of more of triethylamine, dibutylamine, diisopropylamine, potassium carbonate, sodium acetate, cesium carbonate, tetrabutylammonium fluoride and tetrabutylammonium acetate in any proportion;
in the step 4), the borohydride is lithium aluminum hydride, sodium borohydride, potassium borohydride or tetrahydrofuran borane
Figure BDA0002558859050000041
Or borane dimethyl sulfide complex
Figure BDA0002558859050000042
In the step 5), the oxidant is any one of the following substances: pyridinium chlorochromate (abbreviated as PCC), pyridinium dichromate (abbreviated as PDC), periodate, a mixture of oxalyl chloride and DMSO (dimethyl sulfoxide), a mixture of sodium hypochlorite and Tempo (tetramethylpiperidine nitroxide).
Further, the novel preparation method comprises the following steps:
1) the phenylpropionic acid is subjected to halogenation reaction to prepare an intermediate I-1
Adding phenylpropionic acid, organic acid, water, concentrated sulfuric acid, halide salt and halogen molecules into a three-neck flask, stirring and heating to a reflux state, adding sodium bisulfite to reduce the residual halogen molecules after the reaction is finished, extracting by using an organic solvent, washing by using water to be neutral, removing a water layer, and performing reduced pressure desolventizing on the organic layer to obtain a white solid, namely an intermediate I-1; the halogen molecule is chlorine, bromine or iodine particles;
2) the intermediate I-1 is subjected to esterification reaction to prepare an intermediate I-2
Adding saturated fatty alcohol R into a three-mouth bottle1OH, propionic acid and an intermediate I-1 are stirred to be completely dissolved, concentrated sulfuric acid is slowly added, the temperature is raised to reflux, the reaction is kept at the temperature until no raw material is left, water is added, and the intermediate I-2 is obtained by carrying out reduced pressure distillation on an organic layer after extraction and water washing;
3) the intermediate I-2 is subjected to Sonogashira cross-coupling reaction to obtain I-3
Adding a solvent, an alkali and the intermediate I-2 into a three-neck flask, introducing nitrogen, evacuating, heating to 20-50 ℃, adding a catalyst and triphenylphosphine, introducing an ethynylation reagent, reacting, filtering, adding water and an organic solvent, extracting, pickling, washing with water, performing reduced pressure desolventizing on an organic layer, and crystallizing to obtain an intermediate I-3;
4) the intermediate I-3 is subjected to reduction reaction by a reducing agent to obtain I-4
Adding I-3 into a reaction bottle, adding a solvent for dissolution, controlling the temperature, adding a reducing agent, after the reaction is finished, hydrolyzing, extracting by using an organic solvent, carrying out acid washing and water washing, and carrying out reduced pressure desolventizing on an organic layer to obtain an intermediate I-4;
5) the intermediate I-4 is subjected to oxidation reaction to obtain I-5
Adding 1-4 parts of organic solvent into a three-necked bottle, uniformly mixing to form a mixed solution, cooling to-20 ℃, dropwise adding an oxidant at the temperature for reaction, adding sodium bisulfite after dropwise adding, stirring, separating an organic layer, extracting a water layer, washing the organic layer with saline water, and performing reduced pressure desolventizing to obtain an intermediate I-5;
6) the intermediate I-5 is subjected to oxidation reaction to obtain the 3-alkenyl benzyne liquid crystal compound
Adding a solvent and bromomethane triphenylphosphine salt into a three-neck flask, cooling, adding alkali under the nitrogen atmosphere, preserving heat, dropwise adding I-5, preserving heat until the reaction is finished, washing with water, performing vacuum desolventization, passing through a column and crystallizing to obtain white powder, namely the 3-alkenyl benzyne liquid crystal compound.
Further, in the step 1), the organic acid is saturated fatty acid, and the saturated fatty acid is acetic acid, propionic acid or butyric acid; preferably, the saturated fatty acid is acetic acid;
in the step 1), the halate is one or a mixture of more of sodium chlorate, potassium chlorate, sodium bromate, potassium bromate, sodium iodate and potassium iodate;
in the step 1), the dosage ratio of the phenylpropionic acid, the halate and the halogen molecule is 1 mol: 0.1-0.5 mol: 0.2 to 1 mol.
Further, in the step 2), the saturated aliphatic alcohol is methanol, ethanol, propanol or isopropanol; preferably, the saturated aliphatic alcohol is methanol or ethanol;
in the step 2), the mass ratio of the intermediate I-1 to the methanol to the sulfuric acid is 1 g: 2 g-10 g: 0.02g to 0.2 g; preferably, the mass ratio of the intermediate I-1 to the methanol to the sulfuric acid is 1 g: 3 g-5 g: 0.05g to 0.15 g.
Further, in the step 3), the organic solvent is any one or a mixture of N, N-dimethylformamide dimethyl sulfoxide and N, N-dimethylacetamide;
in the step 3), the catalyst is transition metal catalyst, and the transition metal catalyst is Pd (PPh)3)Cl2、Pd(OAc)2，Pd(dppf)Cl2Or bis [ di-tert-butyl- (4-dimethylaminophenyl) phosphine ] palladium (II) dichloride;
in the step 3), the ethynylation reagent is acetylene gas, calcium carbide, acetylene lithium, ethynyl magnesium bromide or sodium acetylide; preferably, the ethynylation reagent is acetylene gas or calcium carbide.
In the step 3), preferably, the base is triethylamine, dibutylamine, potassium carbonate or tetrabutylammonium fluoride;
in the step 3), the weight ratio of the intermediate I-2 to the catalyst is 1: 0.01 to 0.0001; the reaction temperature is 20 ℃ to 140 ℃, preferably 20 ℃ to 40 ℃.
Further, in the step 4), the reducing agent is sodium borohydride, potassium borohydride or tetrahydrofuran borane
Figure BDA0002558859050000061
Any one of the above;
the solvent is methanol, tetrahydrofuran, toluene, ethanol or acetone; the reaction temperature is-20 ℃ to 100 ℃; the molar ratio of the intermediate I-3 to the reducing agent is 1 mol: 3 to 9 mol.
Further, in the step 5), the oxidizing agent is a mixture of sodium hypochlorite and Tempo or periodate; the organic solvent is acetonitrile, dichloromethane, ethyl acetate or dichloroethane; preferably, the organic solvent is dichloromethane or ethyl acetate;
in the step 5), the reaction temperature is-5 ℃ to 10 ℃; the molar ratio of the intermediate I-4 to the oxidant is 1 mol: 0.8mol to 1.2mol, and the preferable molar ratio of the intermediate I-4 to the oxidant is 1 mol: 1mol to 1.1 mol.
Further, in step 6), the base is potassium tert-butoxide, sodium tert-butoxide, butyllithium, sodium hydride, potassium hydride, Lithium Diisopropylamide (LDA) or lithium hexamethyldisilazide (LiHMDS); preferably, the base is potassium tert-butoxide or sodium hydride;
in the step 6), the solvent is Tetrahydrofuran (THF), dichloromethane, toluene or methyl tert-butyl ether; preferably, the solvent is tetrahydrofuran or toluene;
in the step 6), the reaction temperature is-20 ℃ to 20 ℃; preferably, the reaction temperature is-5 ℃ to 15 ℃;
in the step 6), the molar ratio of the intermediate I-5, the alkali and the bromomethane triphenylphosphine salt is 1 mol: 1.8 mol-3 mol: 1.8-2.8 mol; preferably, the molar ratio of the intermediate I-5, the base and the bromomethane triphenylphosphine salt is 1 mol: 2-2.5 mol: 2 to 2.4 mol.
The invention has the beneficial effects that:
(1) according to the invention, low-cost phenylpropionic acid is adopted as a raw material, iodination, esterification, coupling, reduction and oxidation are carried out, and finally, a terminal olefin Wittig reaction is adopted, so that the method has high position selectivity, double bond migration and the like caused by Heck side reaction in the existing synthetic method can be avoided, the quality is improved, and the cost is reduced;
(2) the invention adopts a copper-free cocatalyst (such as CuI), which can greatly eliminate Glaser side reaction, the effective utilization rate of the synthetic raw materials is high, and the synthetic efficiency is greatly improved;
(3) the designed synthesis route is unique, the process route is reasonable, the post-treatment method is simple and easy to implement, and the industrial mass production is facilitated; the prepared product has excellent quality, the gas chromatography purity of the product can reach more than 99.95 percent, and the method is completely suitable for the current requirements of high quality and high quality of liquid crystal materials.
Drawings
FIG. 1 is a graph of mass spectrometry of the compound of I-4 in the example;
FIG. 2 is a H-NMR analysis chart of the compound of example I-4;
FIG. 3 is a graph of mass spectrometry of the compound I-6 in the example;
FIG. 4 is an H-NMR analysis chart of the compound of example I-6.
Detailed Description
The present invention will be described in detail with reference to the following embodiments in order to make the aforementioned objects, features and advantages of the invention more comprehensible. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
Example 1
Preparation method of bis- [4- (3-butene) ] -1, 1' -diphenylacetylene liquid crystal compound
Step 1 preparation of intermediate I-1:
Figure BDA0002558859050000071
66g of phenylpropionic acid, 1000ml of acetic acid, 270ml of water, 25ml of concentrated sulfuric acid, 25g of sodium iodate and 25g of iodine granules are sequentially added into a three-neck flask, stirred and heated to a reflux state, the temperature is about 105 ℃, and the reaction is carried out for 8 hours. And (3) stopping heating after the post-treatment, cooling the system to 50 ℃, adding a sodium bisulfite solution to ensure that the system fades to light yellow and a solid is separated out, adding deionized water, adding toluene for extraction, washing with water, performing vacuum desolventizing, and crystallizing to obtain 86g of intermediate I-1 white powder with the yield of 70%.
Step 2 preparation of intermediate I-2:
Figure BDA0002558859050000072
150ml of anhydrous methanol and 85g of p-iodophenylpropionic acid are added into a three-neck flask, after stirring and full dissolution, 5ml of concentrated sulfuric acid is slowly added, the temperature is raised to 75-80 ℃, reflux is carried out, and the reaction is carried out for 5 hours under the condition of heat preservation. Cooling the mixture to 25 ℃ with cooling water, slowly adding saturated sodium bicarbonate solution, taking care of exhausting air to prevent flushing, stirring for 30min, adding ethyl acetate for extraction, washing with water, performing vacuum desolventizing, and crystallizing to obtain 85g of I-2 pale yellow liquid with the yield of 95%.
Step 3 preparation of intermediate I-3
Figure BDA0002558859050000081
600ml of DMF, 50ml of dibutylamine, 85g of methyl p-iodophenylpropionate are added into a three-necked flask, nitrogen is introduced, the mixture is heated to 30 ℃, stirred for 30min, air is exhausted, 0.05g of bis [ di-tert-butyl- (4-dimethylaminophenyl) phosphine ] -palladium (II) dichloride and 24g of triphenylphosphine are added, acetylene gas is introduced, the reaction is continued for 12h, triethylamine is evaporated after the reaction is finished, diluted hydrochloric acid is adjusted to be neutral, toluene and saturated salt water are added for washing twice. Ethyl acetate was added for extraction, water washing, vacuum desolventizing, and crystallization to give 44g of I-3 white powder with a yield of 85%.
Step 4 preparation of intermediate I-4
Figure BDA0002558859050000082
40g I-3 was added to a three-necked flask, followed by addition of 140ml THF, stirring and dissolution, cooling to-10 deg.C, and addition of 30g sodium borohydride. After stirring for 30min, 30g of methanol were added dropwise. The temperature is controlled below 30 ℃ in the dropping process, and the temperature is kept about 30 ℃ after dropping. After the reaction, dilute hydrochloric acid is adjusted to be neutral, and toluene and saturated salt water are added for washing twice. Ethyl acetate is added for extraction, water washing, vacuum desolventizing and crystallization are carried out, 32g of I-4 white flaky crystals are obtained, the yield is 95%, the mass spectrum analysis chart is shown in figure 1, the H-NMR analysis chart is shown in figure 2, and the analysis product is the target product.
Step 5 preparation of intermediate I-5:
Figure BDA0002558859050000083
29.4g of intermediate I-4, 450ml of ethyl acetate, 1g of Tempo and 2g of potassium bromide are sequentially added into a three-necked bottle, after stirring and full dissolution, the temperature is reduced to-10 ℃, a prepared sodium hypochlorite solution (formed by mixing 95g of a sodium hypochlorite solution with 13.5 percent of chlorine content with 15g of a 10 percent sodium bicarbonate solution) is dripped, the temperature is controlled to be-5 ℃ in the dripping process, and the temperature is kept below 10 ℃ for 15 minutes after the dripping is finished.
After the raw materials react, 10% sodium bisulfite is added, the mixture is stirred for 30min, the mixture is kept stand and separated, an organic layer is washed to be neutral by saturated salt water, dried by anhydrous sodium sulfate and desolventized in vacuum, and 24.6g of I-5 pale yellow solid is obtained, and the solid is obtained by GC: 95% and yield 85%.
Step 6 preparation of intermediate I-6:
Figure BDA0002558859050000084
400ml of tetrahydrofuran and 65g of bromomethane triphenylphosphine salt are added into a three-neck flask, the temperature is reduced to be below minus 10 ℃, 22g of potassium tert-butoxide is added under the nitrogen atmosphere, the exothermic condition of the system is observed, and after the addition is finished, the temperature is kept below 0 ℃ for reaction for 2 hours. The temperature of the system is reduced to below 0 ℃, the prepared I-5 solution (prepared by 24g of intermediate I-5 and 120ml of tetrahydrofuran) is dripped, and the temperature is controlled to below 5 ℃ in the dripping process. After dripping, the reaction is carried out for 2h at the temperature below 20 ℃. Adding deionized water (0-5 deg.C) with temperature lowered in advance, controlling temperature at 0-5 deg.C, stirring for 30min, separating organic layer, and washing with saturated salt water to neutrality. Vacuum desolventizing, passing through silica gel column, crystallizing to obtain 20.4g white powder, GC: 99.95%, yield 85%, mass spectrometry as shown in figure 3, H-NMR as shown in figure 4, and analyzed product as target product.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims (9)

1. A novel preparation method of a 3-alkenyl benzyne liquid crystal compound is characterized by comprising the following steps:
1) taking phenylpropionic acid as a raw material, and preparing an intermediate I-1 through halogenation;
Figure FDA0002558859040000011
2) the intermediate I-1 and alcohol are subjected to esterification reaction under the catalysis of acid or acyl chloride to prepare an intermediate I-2;
Figure FDA0002558859040000012
3) carrying out Sonogashira cross-coupling reaction on the intermediate I-2 and an ethynylation reagent under an alkaline condition and in the presence of a transition metal catalyst to obtain I-3;
Figure FDA0002558859040000013
4) i-3, preparing I-4 under the reduction of borohydride;
Figure FDA0002558859040000014
5) i-4 is selectively oxidized under the action of an oxidant to prepare I-5;
Figure FDA0002558859040000015
6) i-5 and a wittig reagent prepared from bromomethane triphenylphosphine salt and alkali are subjected to wittig reaction to prepare the 3-alkenyl phenylalkyne liquid crystal compound I;
Figure FDA0002558859040000016
wherein R is1Is an alkyl group having 1 to 7 carbon atoms; r2An alkyl group having 1 to 5 carbon atoms; x is halogen, including chlorine, bromine or iodine.
2. The novel process for preparing 3-alkenylbenzyne liquid crystal compounds according to claim 1, wherein in the step 1), the halogenation reaction with phenylpropionic acid is performed by using a chlorination reagent, a bromination reagent or an iodination reagent;
in the step 2), the acid is sulfuric acid, phosphoric acid or boron trifluoride diethyl etherate, the acyl chloride is oxalyl chloride or thionyl chloride, and the alcohol is saturated fatty alcohol;
in the step 3), the transition metal catalyst is Pd (PPh)3)Cl2、Pd(OAc)21, 1' -bis (diphenylphosphino) ferrocene dichloropalladium (II), Pd (dba)3Or one or a plurality of bis (di-tert-butyl- (4-dimethylaminophenyl) phosphine) palladium dichloride (II) in any proportion;
in the step 3), the ethynylation reagent is acetylene gas, calcium carbide or acetylene derivatives; the alkaline condition is one or a mixture of more of triethylamine, dibutylamine, diisopropylamine, potassium carbonate, sodium acetate, cesium carbonate, tetrabutylammonium fluoride and tetrabutylammonium acetate in any proportion;
in the step 4), the borohydride is lithium aluminum hydride, sodium borohydride, potassium borohydride, tetrahydrofuran borane or borane dimethyl sulfide complex;
in the step 5), the oxidant is any one of the following substances: PCC, PDC, periodate, a mixture of oxalyl chloride and DMSO, a mixture of sodium hypochlorite and Tempo.
3. The novel process for producing a 3-alkenylphenylalkyne liquid crystal compound according to claim 1 or 2, wherein the novel process comprises the steps of:
1) the phenylpropionic acid is subjected to halogenation reaction to prepare an intermediate I-1
Adding phenylpropionic acid, organic acid, water, concentrated sulfuric acid, halide salt and halogen molecules into a three-neck flask, stirring and heating to a reflux state, adding sodium bisulfite to reduce the residual halogen molecules after the reaction is finished, extracting by using an organic solvent, washing by using water to be neutral, removing a water layer, and performing reduced pressure desolventizing on the organic layer to obtain a white solid, namely an intermediate I-1; the halogen molecule is chlorine, bromine or iodine particles;
2) the intermediate I-1 is subjected to esterification reaction to prepare an intermediate I-2
Adding saturated fatty alcohol R into a three-mouth bottle1OH, propionic acid and an intermediate I-1 are stirred to be completely dissolved, concentrated sulfuric acid is slowly added, the temperature is raised to reflux, the reaction is kept at the temperature until no raw material is left, water is added, and the intermediate I-2 is obtained by carrying out reduced pressure distillation on an organic layer after extraction and water washing;
3) the intermediate I-2 is subjected to Sonogashira cross-coupling reaction to obtain I-3
Adding a solvent, an alkali and the intermediate I-2 into a three-neck flask, introducing nitrogen, evacuating, heating to 20-50 ℃, adding a catalyst and triphenylphosphine, introducing an ethynylation reagent, reacting, filtering, adding water and an organic solvent, extracting, pickling, washing with water, performing reduced pressure desolventizing on an organic layer, and crystallizing to obtain an intermediate I-3;
4) the intermediate I-3 is subjected to reduction reaction by a reducing agent to obtain I-4
Adding I-3 into a reaction bottle, adding a solvent for dissolution, controlling the temperature, adding a reducing agent, after the reaction is finished, hydrolyzing, extracting by using an organic solvent, carrying out acid washing and water washing, and carrying out reduced pressure desolventizing on an organic layer to obtain an intermediate I-4;
5) the intermediate I-4 is subjected to oxidation reaction to obtain I-5
Adding 1-4 parts of organic solvent into a three-necked bottle, uniformly mixing to form a mixed solution, cooling to-20 ℃, dropwise adding an oxidant at the temperature for reaction, adding sodium bisulfite after dropwise adding, stirring, separating an organic layer, extracting a water layer, washing the organic layer with saline water, and performing reduced pressure desolventizing to obtain an intermediate I-5;
6) the intermediate I-5 is subjected to oxidation reaction to obtain the 3-alkenyl benzyne liquid crystal compound
Adding a solvent and bromomethane triphenylphosphine salt into a three-neck flask, cooling, adding alkali under the nitrogen atmosphere, preserving heat, dropwise adding I-5, preserving heat until the reaction is finished, washing with water, performing vacuum desolventization, passing through a column and crystallizing to obtain white powder, namely the 3-alkenyl benzyne liquid crystal compound.
4. The novel process for preparing 3-alkenylbenzyne liquid crystal compounds according to claim 3, wherein in step 1), the organic acid is a saturated fatty acid, and the saturated fatty acid is acetic acid, propionic acid or butyric acid; the halide is one or a mixture of more of sodium chlorate, potassium chlorate, sodium bromate, potassium bromate, sodium iodate and potassium iodate;
the dosage ratio of the phenylpropionic acid, the halate and the halogen molecule is 1 mol: 0.1-0.5 mol: 0.2 to 1 mol.
5. The novel process for preparing 3-alkenylbenzyne liquid crystal compounds according to claim 3, wherein in the step 2), the saturated aliphatic alcohol is methanol, ethanol, propanol or isopropanol; the mass ratio of the intermediate I-1 to the methanol to the sulfuric acid is 1 g: 2 g-10 g: 0.02g to 0.2 g.
6. The novel process for preparing 3-alkenylbenzyne liquid crystal compounds according to claim 3, wherein in the step 3), the organic solvent is one or a mixture of N, N-dimethylformamide dimethyl sulfoxide and N, N-dimethylacetamide;
the catalyst is transition metal catalyst, and the transition metal catalyst is Pd (PPh)3)Cl2、Pd(OAc)2，Pd(dppf)Cl2Or bis [ di-tert-butyl- (4-dimethylaminophenyl) phosphine ] palladium (II) dichloride;
the ethynylation reagent is acetylene gas, calcium carbide, lithium acetylene, ethynyl magnesium bromide or sodium ethynylation;
the alkali is triethylamine, dibutylamine, potassium carbonate or tetrabutylammonium fluoride;
the weight ratio of the intermediate I-2 to the catalyst is 1: 0.01 to 0.0001; the reaction temperature is 20-140 ℃.
7. The novel method for preparing a 3-alkenylbenzyne liquid crystal compound according to claim 3, wherein in the step 4), the reducing agent is any one of sodium borohydride, potassium borohydride or tetrahydrofuran borane;
the solvent is methanol, tetrahydrofuran, toluene, ethanol or acetone; the reaction temperature is-20 ℃ to 100 ℃; the molar ratio of the intermediate I-3 to the reducing agent is 1 mol: 3 to 9 mol.
8. The novel method for preparing a 3-alkenylbenzyne liquid crystal compound according to claim 3, wherein in the step 5), the oxidant is a mixture of sodium hypochlorite and Tempo or periodate; the organic solvent is acetonitrile, dichloromethane, ethyl acetate or dichloroethane; the reaction temperature is-5 ℃ to 10 ℃; the molar ratio of the intermediate I-4 to the oxidant is 1 mol: 0.8mol to 1.2 mol.
9. The novel process for preparing 3-alkenylbenzyne liquid crystal compounds according to claim 3, wherein in step 6), the base is potassium tert-butoxide, sodium tert-butoxide, butyllithium, sodium hydride, potassium hydride, lithium diisopropylamide, or lithium hexamethyldisilazide; the solvent is tetrahydrofuran, dichloromethane, toluene or methyl tert-butyl ether;
the reaction temperature is-20 ℃ to 20 ℃; the molar ratio of the intermediate I-5 to the alkali to the bromomethane triphenylphosphine salt is 1 mol: 1.8 mol-3 mol: 1.8mol to 2.8 mol.
CN202010605590.6A 2020-06-29 2020-06-29 Novel preparation method of 3-alkenyl benzyne liquid crystal compound Pending CN111704912A (en)

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