CN110655462A - Preparation method of p-acetoxystyrene - Google Patents
Preparation method of p-acetoxystyrene Download PDFInfo
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- CN110655462A CN110655462A CN201910910640.9A CN201910910640A CN110655462A CN 110655462 A CN110655462 A CN 110655462A CN 201910910640 A CN201910910640 A CN 201910910640A CN 110655462 A CN110655462 A CN 110655462A
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- JAMNSIXSLVPNLC-UHFFFAOYSA-N (4-ethenylphenyl) acetate Chemical compound CC(=O)OC1=CC=C(C=C)C=C1 JAMNSIXSLVPNLC-UHFFFAOYSA-N 0.000 title claims abstract 14
- 238000002360 preparation method Methods 0.000 title abstract 4
- 238000006243 chemical reaction Methods 0.000 claims abstract 25
- TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 claims abstract 12
- VZOVSXXHXIMTQX-UHFFFAOYSA-N [4-(1-hydroxyethyl)phenyl] acetate Chemical compound CC(O)C1=CC=C(OC(C)=O)C=C1 VZOVSXXHXIMTQX-UHFFFAOYSA-N 0.000 claims abstract 6
- 230000021736 acetylation Effects 0.000 claims abstract 5
- 238000006640 acetylation reaction Methods 0.000 claims abstract 5
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract 5
- SMIOEQSLJNNKQF-UHFFFAOYSA-N 4-acetoxy acetophenone Chemical compound CC(=O)OC1=CC=C(C(C)=O)C=C1 SMIOEQSLJNNKQF-UHFFFAOYSA-N 0.000 claims abstract 4
- 238000003379 elimination reaction Methods 0.000 claims abstract 3
- 239000002904 solvent Substances 0.000 claims 11
- 238000000034 method Methods 0.000 claims 6
- 239000002253 acid Substances 0.000 claims 5
- 239000002585 base Substances 0.000 claims 4
- 239000003054 catalyst Substances 0.000 claims 4
- 150000007529 inorganic bases Chemical class 0.000 claims 4
- 238000004519 manufacturing process Methods 0.000 claims 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 3
- 239000011230 binding agent Substances 0.000 claims 3
- 239000003960 organic solvent Substances 0.000 claims 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims 2
- 150000008041 alkali metal carbonates Chemical group 0.000 claims 2
- 239000003759 ester based solvent Substances 0.000 claims 2
- 150000004679 hydroxides Chemical class 0.000 claims 2
- 239000007788 liquid Substances 0.000 claims 2
- 150000007530 organic bases Chemical group 0.000 claims 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims 2
- 239000002516 radical scavenger Substances 0.000 claims 2
- 238000000926 separation method Methods 0.000 claims 2
- FMFHUEMLVAIBFI-UHFFFAOYSA-N 2-phenylethenyl acetate Chemical compound CC(=O)OC=CC1=CC=CC=C1 FMFHUEMLVAIBFI-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 claims 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims 1
- 239000012346 acetyl chloride Substances 0.000 claims 1
- 239000005456 alcohol based solvent Substances 0.000 claims 1
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 1
- 239000003513 alkali Substances 0.000 claims 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 claims 1
- 229910052783 alkali metal Inorganic materials 0.000 claims 1
- 150000001340 alkali metals Chemical class 0.000 claims 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims 1
- 150000001342 alkaline earth metals Chemical class 0.000 claims 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims 1
- 238000002425 crystallisation Methods 0.000 claims 1
- 230000008025 crystallization Effects 0.000 claims 1
- 239000004210 ether based solvent Substances 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 239000005453 ketone based solvent Substances 0.000 claims 1
- 239000007791 liquid phase Substances 0.000 claims 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims 1
- 229910052759 nickel Inorganic materials 0.000 claims 1
- 239000012074 organic phase Substances 0.000 claims 1
- 239000003880 polar aprotic solvent Substances 0.000 claims 1
- 229910000027 potassium carbonate Inorganic materials 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 229910000029 sodium carbonate Inorganic materials 0.000 claims 1
- 150000003512 tertiary amines Chemical group 0.000 claims 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 claims 1
- 238000005406 washing Methods 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
- 238000007171 acid catalysis Methods 0.000 abstract 2
- 150000001336 alkenes Chemical class 0.000 abstract 2
- 230000008030 elimination Effects 0.000 abstract 2
- 238000005755 formation reaction Methods 0.000 abstract 2
- 230000007547 defect Effects 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- 238000007086 side reaction Methods 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/14—Preparation of carboxylic acid esters from carboxylic acid halides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
- C07C67/29—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by introduction of oxygen-containing functional groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the field of organic chemistry, in particular to a preparation method of p-acetoxystyrene. The preparation method of the p-acetoxystyrene provided by the invention comprises the following steps: reacting p-hydroxyacetophenone with an acetylation reagent to prepare p-acetoxyacetophenone; hydrogenating and reducing p-acetoxyacetophenone to obtain 1- (4-acetoxyphenyl) ethanol; the p-acetoxystyrene is prepared by eliminating reaction of 1- (4-acetoxyphenyl) ethanol. The preparation method of p-acetoxystyrene provided by the invention starts from the most basic raw materials, and is carried out through three steps of reactions, particularly in the third step of alkene formation reaction, alkaline elimination is originally adopted, so that the defects that the traditional alkene formation reaction by acid catalysis elimination is easy to generate double-bond acid catalysis flash side reaction, the reaction is easy to lose control, the yield is low and the like are avoided, and the generated double bonds can stably exist for a long time under a reaction system.
Description
Technical Field
The invention relates to the field of organic chemistry, in particular to a preparation method of p-acetoxystyrene.
Background
The poly-p-hydroxystyrene can be applied to the material chemistry fields of chemical adhesives, coatings and the like, has important application particularly in the fields of integrated circuit etching and chip manufacturing, and is a main component of a chemical amplification type photoresist. The p-acetoxystyrene is an important monomer compound for synthesizing the poly-p-hydroxystyrene.
Many of the known methods for synthesizing p-acetoxystyrene are based on p-hydroxybenzaldehyde or p-hydroxyacetophenone and are synthesized by a multi-step reaction. Patents US431699, US2004118673, US2005228191, etc. describe a process for synthesizing a styrene dicarboxylic acid intermediate by reacting p-hydroxybenzaldehyde with malonic acid, followed by two decarboxylation and acetylation steps to obtain acetoxystyrene. JP2002179621 provides a method of converting aldehyde groups of p-hydroxybenzaldehyde or p-acetoxybenzaldehyde into ethylene groups via Wittig reaction. The routes provided by US5041614, US5563289, CN1854116 and CN10279599 are that p-hydroxyacetophenone is used as a starting material, and the p-acetoxyphenyl methyl methanol intermediate is obtained through acetylation, reduction and other steps, and then the intermediate is subjected to thermal elimination dehydration reaction under the catalysis of acid to obtain the product. These methods have disadvantages such as expensive reagents, complicated processes, and low yield.
Disclosure of Invention
In view of the above-mentioned drawbacks of the prior art, the present invention aims to provide a method for preparing p-acetoxystyrene, which solves the problems of the prior art.
To achieve the above and other related objects, the present invention provides a method for preparing p-acetoxystyrene, comprising:
1) p-hydroxyacetophenone is reacted with an acetylation reagent to prepare p-acetoxyacetophenone, and the reaction equation is as follows:
2) the p-acetoxyacetophenone is hydrogenated and reduced to prepare the 1- (4-acetoxyphenyl) ethanol, and the reaction equation is as follows:
3) the p-acetoxystyrene is prepared by carrying out elimination reaction on 1- (4-acetoxyphenyl) ethanol, and the reaction equation is as follows:
in some embodiments of the present invention, in the step 1), the reaction is performed in the presence of an acid-binding agent.
In some embodiments of the invention, in step 1), the acid scavenger is selected from a base.
In some embodiments of the present invention, in the step 1), the acid scavenger is selected from an organic base and/or an inorganic base.
In some embodiments of the present invention, in step 1), the organic base is selected from tertiary amines, preferably selected from one or more of triethylamine, tributylamine, diisopropylethylamine in combination.
In some embodiments of the present invention, in step 1), the inorganic base is selected from alkali metal carbonates, preferably selected from a combination of one or more of sodium carbonate and potassium carbonate.
In some embodiments of the present invention, in the step 1), the molar ratio of the p-hydroxyacetophenone to the acid-binding agent is 1: 1 to 5.
In some embodiments of the present invention, in the step 1), the molar ratio of the p-hydroxyacetophenone to the acid-binding agent is 1: 1.1 to 1.5.
In some embodiments of the invention, in step 1), the reaction is carried out in the presence of a solvent selected from organic solvents.
In some embodiments of the present invention, in the step 1), the solvent is selected from one or more of ester solvents, carbonate solvents, ketone solvents, ether solvents, halogenated alkane solvents, and acetic acid.
In some embodiments of the present invention, in the step 1), the reaction temperature is 10 to 80 ℃.
In some embodiments of the present invention, in the step 1), the reaction temperature is 20 to 50 ℃.
In some embodiments of the present invention, in the step 1), the molar ratio of p-hydroxyacetophenone to the acetylating agent is 1: 1 to 2.
In some embodiments of the present invention, in the step 1), the molar ratio of p-hydroxyacetophenone to the acetylating agent is 1: 1.2 to 1.5.
In some embodiments of the invention, in step 1), the acetylating reagent is selected from one or more of acetyl chloride, acetic anhydride, and combinations thereof.
In some embodiments of the invention, in step 1), the post-treatment of the reaction comprises: solid-liquid separation and liquid-phase crystallization.
In some embodiments of the invention, in step 2), the reaction is carried out in the presence of a catalyst.
In some embodiments of the present invention, in the step 2), the catalyst is selected from one or more of a palladium carbon based catalyst and a nickel based catalyst.
In some embodiments of the invention, in step 2), the reaction is carried out in the presence of a solvent selected from organic solvents.
In some embodiments of the present invention, in the step 2), the solvent is selected from one or more of ester solvents, carbonate solvents, alcohol solvents and aromatic hydrocarbon solvents.
In some embodiments of the present invention, in the step 2), the reaction temperature is 10 to 80 ℃.
In some embodiments of the present invention, in the step 2), the reaction temperature is 20 to 50 ℃.
In some embodiments of the invention, in the step 2), the reaction pressure is 3 to 15 bar.
In some embodiments of the present invention, in the step 2), the reaction pressure is 5 to 10 bar.
In some embodiments of the invention, in step 2), the reaction is carried out under a reducing atmosphere.
In some embodiments of the invention, in step 2), the reducing atmosphere is selected from a hydrogen atmosphere.
In some embodiments of the invention, in step 2), the post-treatment of the reaction comprises: solid-liquid separation, desolventizing and purification.
In some embodiments of the invention, in step 3), the reaction is carried out in the presence of a base.
In some embodiments of the invention, in step 3), the base is selected from inorganic bases.
In some embodiments of the present invention, in the step 3), the inorganic base is selected from one or more of hydroxides of alkali metals and hydroxides of alkaline earth metals, and more preferably selected from one or more of NaOH, KOH and LiOH.
In some embodiments of the invention, in step 3), the molar ratio of 1- (4-acetoxyphenyl) ethanol to base is 1: 0.8 to 5.
In some embodiments of the invention, in step 3), the molar ratio of 1- (4-acetoxyphenyl) ethanol to base is 1: 1 to 3.
In some embodiments of the invention, in step 3), the reaction is carried out in the presence of a solvent selected from polar aprotic solvents.
In some embodiments of the invention, in step 3), the solvent is selected from DMAC, DMF, NMP, or a combination of one or more thereof.
In some embodiments of the present invention, in the step 3), the reaction temperature is 80 to 150 ℃.
In some embodiments of the present invention, in the step 3), the reaction temperature is 100 to 130 ℃.
In some embodiments of the invention, in step 3), the post-treatment of the reaction comprises: desolventizing, washing with water, extracting with an organic solvent, desolventizing the organic phase, and purifying.
Detailed Description
The present inventors have made extensive studies and have provided a novel method for producing acetoxystyrene, which has the advantages of stable reaction system, high yield, small amplification effect and the like, and is more suitable for industrial scale-up production.
The invention provides a preparation method of acetoxystyrene, which comprises the following steps:
1) reacting p-hydroxyacetophenone with an acetylation reagent to prepare p-acetoxyacetophenone;
2) hydrogenating and reducing p-acetoxyacetophenone to obtain 1- (4-acetoxyphenyl) ethanol;
3) the p-acetoxystyrene is prepared by eliminating reaction of 1- (4-acetoxyphenyl) ethanol.
The preparation method of acetoxystyrene provided by the invention can comprise acetylation reaction, and the acetylation reaction can specifically comprise: p-hydroxyacetophenone is reacted with an acetylation reagent to prepare p-acetoxyacetophenone, and the reaction equation is as follows:
in the present invention, the acetylation reaction is usually carried out in the presence of an acid-binding agent, so that alkaline reaction conditions can be provided and the acid generated during the reaction can be neutralized. The person skilled in the art can select an appropriate kind and amount of acid scavenger for the acetylation reaction, for example, the acid scavenger is usually a base, specifically an organic base and/or an inorganic base, and in a specific embodiment of the present invention, the acid scavenger may be selected from alkali metal carbonate, tertiary amine, and the like, and more specifically may be a combination of one or more of sodium carbonate, potassium carbonate, triethylamine, tributylamine, diisopropylethylamine, and the like; for another example, the amount of the acid-binding agent may be 1 to 5 times, 1 to 1.5 times, 1.5 to 2 times, 2 to 3 times, 3 to 4 times, or 4 to 5 times, preferably 1.1 to 1.5 times the amount of the p-hydroxyacetophenone compound.
In the present invention, in the acetylation reaction, the reaction is usually performed in the presence of a solvent, which is usually a good solvent of the reaction system, and one skilled in the art can select an appropriate kind and amount of solvent for the acetylation reaction, for example, the solvent used in the acetylation reaction may be selected from organic solvents and the like, and may be specifically selected from one or a combination of more of ester solvents, carbonate solvents, ketone solvents, ether solvents, haloalkane solvents, acetic acid and the like. In one embodiment of the present invention, the solvent used in the acetylation reaction may be selected from one or more of ethyl acetate, dimethyl carbonate, acetone, tetrahydrofuran, dichloromethane, dichloroethane, acetic acid, and the like, and preferably may be selected from one or more of ethyl acetate, dimethyl carbonate, dichloromethane, acetic acid, and the like. For another example, in the acetylation reaction, the mass of the solvent used may be 1 to 10 times, 1 to 2 times, 2 to 4 times, 4 to 6 times, 6 to 8 times, or 8 to 10 times, preferably 2 to 6 times, that of the p-hydroxyacetophenone.
In the present invention, the reaction in the acetylation reaction may be performed at a temperature ranging from room temperature to the boiling point of the solvent, for example, the reaction temperature of the acetylation reaction may be 10 to 80 ℃, 10 to 20 ℃, 20 to 30 ℃, 30 to 40 ℃, 40 to 50 ℃, 50 to 60 ℃, 60 to 70 ℃, or 70 to 80 ℃, and preferably 20 to 50 ℃. The reaction time of the acetylation reaction can be adjusted by one skilled in the art according to the reaction progress, for example, the reaction progress of the acetylation reaction can be determined by TLC, chromatography, etc., and for example, the reaction time of the acetylation reaction can be 1 to 24 hours, 1 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, or 12 to 24 hours.
In the present invention, in the acetylation reaction, a person skilled in the art can generally select an appropriate kind and amount of acetylation reagent, for example, the acetylation reagent used in the acetylation reaction can be generally selected from one or more combinations of anhydride acylating agents, acyl chloride acylating agents, and the like, and in a preferred embodiment of the present invention, the acetylation reagent can be selected from one or more combinations of acetyl chloride, acetic anhydride, and the like. The amount of the acetylation reagent is usually substantially equal to or in excess relative to the amount of p-hydroxyacetophenone, so that sufficient reaction of the reaction substrate can be ensured, for example, the molar ratio of p-hydroxyacetophenone to the acetylation reagent may be 1: 1-2 and 1: 1-1.2, 1: 1.2-1.3, 1: 1.3-1.5, 1: 1.5-1.6, 1: 1.6-1.8, or 1: 1.8-2, preferably 1: 1.2 to 1.5.
In the present invention, in the acetylation reaction, the acetylation reagent may be added to the reaction system, which may include p-hydroxyacetophenone, an acid-binding agent, a solvent, etc., usually by a small amount, so as to avoid excessive heat release of the reaction system. The person skilled in the art may select suitable methods for working up the product of the acetylation reaction, which may also include, for example: solid-liquid separation and liquid-phase crystallization. In a specific embodiment of the invention, after the reaction is finished, the product can be filtered, and the liquid phase can be subjected to concentration, recrystallization and other steps to prepare the p-acetoxyacetophenone.
The preparation method of acetoxystyrene provided by the invention can further comprise a reduction reaction, and the reduction reaction can specifically comprise: the p-acetoxyacetophenone is hydrogenated and reduced to prepare the 1- (4-acetoxyphenyl) ethanol, and the reaction equation is as follows:
in the present invention, in the reduction reaction, the reaction is generally carried out in the presence of a catalyst, and a person skilled in the art can select an appropriate kind and amount of the catalyst for the hydrogenation reduction. For example, the catalyst may be selected from one or more of palladium carbon based catalysts, nickel based catalysts, and the like, and in a specific embodiment of the present invention, the catalyst may be one or more of palladium carbon, raney nickel, and the like. The catalyst is generally used in a catalytic amount, for example, the ratio of the mass of the catalyst to the mass of the p-acetoxyacetophenone may be 0.1 to 0.05: 1. 0.05-0.01: 1. 0.01 to 0.005: 1. or 0.005 to 0.001: 1, preferably 0.05 to 0.01: 1.
in the present invention, in the reduction reaction, the reaction is usually carried out in the presence of a solvent, which is usually a good solvent of the reaction system, and a person skilled in the art can select an appropriate kind and amount of solvent for the reduction reaction, for example, the solvent used in the reduction reaction may be selected from organic solvents and the like, and may be specifically selected from one or a combination of more of ester solvents, carbonate solvents, alcohol solvents, aromatic hydrocarbon solvents and the like. In a specific embodiment of the present invention, the solvent used in the reduction reaction may be selected from one or more of ethyl acetate, dimethyl carbonate, methanol, toluene, and the like, and preferably may be selected from one or more of ethyl acetate, methanol, toluene, and the like. For another example, in the reduction reaction, the mass of the solvent used may be 1 to 10 times, 1 to 2 times, 2 to 4 times, 4 to 6 times, 6 to 8 times, or 8 to 10 times, preferably 2 to 6 times, the mass of the solvent used may be 2 to 6 times that of the acetoxyacetophenone.
In the present invention, in the reduction reaction, the reaction may be performed at a temperature ranging from room temperature to the boiling point of the solvent, for example, the reaction temperature of the reduction reaction may be 10 to 80 ℃, 10 to 20 ℃, 20 to 30 ℃, 30 to 40 ℃, 40 to 50 ℃, 50 to 60 ℃, 60 to 70 ℃, or 70 to 80 ℃, and preferably 20 to 50 ℃. The reduction reaction is usually performed under a certain pressure to ensure smooth hydrogenation reduction, for example, the reaction pressure may be 3 to 5bar, 5 to 7bar, 7 to 10bar, or 10 to 15bar, and preferably 5 to 10 bar. The reaction time of the reduction reaction can be adjusted by those skilled in the art according to the reaction progress, for example, the reaction progress of the reduction reaction can be judged by TLC, chromatography, etc., and for example, the reaction time of the reduction reaction can be 1 to 24 hours, 1 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, or 12 to 24 hours.
In the present invention, in the reduction reaction, the reaction is generally carried out under a reducing atmosphere, and for example, may be carried out under a hydrogen atmosphere to provide suitable reduction conditions. The method of forming the reducing atmosphere is known to those skilled in the art, and for example, the atmosphere in the reaction system may be replaced after the reaction raw material and the solvent are mixed, and the atmosphere in the reaction system may be replaced with an inert atmosphere (for example, a nitrogen atmosphere) and then with a hydrogen atmosphere. The person skilled in the art can select suitable methods for working up the product of the reduction reaction, which may also include, for example: solid-liquid separation, desolventizing and purification. In a specific embodiment of the invention, after the reaction is finished, the product can be filtered, and the liquid phase can be concentrated and further distilled to prepare the p-acetoxyacetophenone.
The preparation method of acetoxystyrene provided by the invention can also comprise an elimination reaction, and the elimination reaction can specifically comprise the following steps: the p-acetoxystyrene is prepared by carrying out elimination reaction on 1- (4-acetoxyphenyl) ethanol, and the reaction equation is as follows:
in the elimination reaction of the present invention, the reaction is usually carried out in the presence of a base, so that the occurrence of side reactions such as acid-catalyzed double bond coupling can be avoided. The kind and amount of the base used in the elimination reaction should be selectable by those skilled in the art, for example, the base may be selected from organic bases, inorganic bases, etc., more preferably from a combination of one or more of hydroxides of alkali metals, hydroxides of alkaline earth metals, etc. In one embodiment of the present invention, the base used in the elimination reaction may be selected from one or a combination of more of NaOH, KOH, LiOH, and the like. The base may generally be used in substantially equal amounts or in excess, preferably in excess, relative to the 1- (4-acetoxyphenyl) ethanol to ensure that the reaction proceeds sufficiently forward, for example, the molar ratio of 1- (4-acetoxyphenyl) ethanol to base may be 1: 0.8-5, 1: 0.8-1, 1: 1-1.5, 1: 1.5-2, 1: 2-2.5, 1: 2.5-3, 1: 3-4, or 1: 4 to 5, preferably 1: 1 to 3.
In the elimination reaction of the present invention, the reaction is usually carried out in the presence of a solvent, which is usually a good solvent for the reaction system, and may be an aprotic solvent, more specifically, a polar aprotic solvent. The skilled person can select a suitable kind and amount of solvent for the elimination reaction, for example, the solvent used in the elimination reaction may be selected from organic solvents, and specifically may be selected from one or more combinations of DMAC, DMF, NMP, and the like. For another example, in the elimination reaction, the mass of the solvent used may be 1 to 10 times, 1 to 2 times, 2 to 4 times, 4 to 7 times, or 7 to 10 times, preferably 4 to 7 times that of 1- (4-acetoxyphenyl) ethanol.
In the elimination reaction of the present invention, the reaction may be usually carried out under heating, for example, the reaction temperature of the elimination reaction may be 80 to 150 ℃, 80 to 100 ℃, 100 to 130 ℃, or 130 to 150 ℃, and preferably 100 to 130 ℃. The reaction time of the elimination reaction can be adjusted by those skilled in the art according to the reaction progress, for example, the reaction progress of the esterification reaction can be judged by TLC, chromatography, etc., and for example, the reaction time of the elimination reaction can be 1 to 24 hours, 1 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, or 12 to 24 hours.
In the present invention, in the elimination reaction, a person skilled in the art can select a suitable method to perform post-treatment on the product of the elimination reaction, for example, the elimination reaction may further include: desolventizing, washing with water, extracting with an organic solvent, desolventizing the organic phase, and purifying. In a specific embodiment of the present invention, after the reaction is finished, the product may be desolventized, and then the residue may be dissolved in an organic solvent, washed with water, separated to obtain an organic phase, and subjected to concentration, distillation, and the like to prepare the acetoxystyrene.
The preparation method of p-acetoxystyrene provided by the invention starts from the most basic raw materials, and is carried out through three steps of reactions, particularly in the third step of alkene formation reaction, alkaline elimination is originally adopted, so that the defects that the traditional alkene formation reaction by acid catalysis elimination is easy to generate double-bond acid catalysis flash side reaction, the reaction is easy to lose control, the yield is low and the like are avoided, and the generated double bonds can stably exist for a long time under a reaction system. Therefore, the preparation method of p-acetoxystyrene provided by the invention has the advantages of high yield, small amplification effect, suitability for large-scale production and the like, and has good industrialization prospect.
The embodiments of the present invention are described below with reference to specific embodiments, and other advantages and effects of the present invention will be easily understood by those skilled in the art from the disclosure of the present specification. The invention is capable of other and different embodiments and of being practiced or of being carried out in various ways, and its several details are capable of modification in various respects, all without departing from the spirit and scope of the present invention.
It is to be understood that the processing equipment or apparatus not specifically identified in the following examples is conventional in the art.
Furthermore, it is to be understood that one or more method steps mentioned in the present invention does not exclude that other method steps may also be present before or after the combined steps or that other method steps may also be inserted between these explicitly mentioned steps, unless otherwise indicated; it is also to be understood that a combined connection between one or more devices/apparatus as referred to in the present application does not exclude that further devices/apparatus may be present before or after the combined device/apparatus or that further devices/apparatus may be interposed between two devices/apparatus explicitly referred to, unless otherwise indicated. Moreover, unless otherwise indicated, the numbering of the various method steps is merely a convenient tool for identifying the various method steps, and is not intended to limit the order in which the method steps are arranged or the scope of the invention in which the invention may be practiced, and changes or modifications in the relative relationship may be made without substantially changing the technical content.
Example 1
Synthesis of p-acetoxyacetophenone:
at 10L4080g of ethyl acetate, 1360g of p-hydroxyacetophenone and 1272g of sodium carbonate are sequentially added into a reaction bottle, stirring is started, and 1335g of acetyl chloride is dropwise added at the temperature of 20-30 ℃. Continuing to keep the temperature and stir for 8 hours after the dropwise addition is finished, filtering, washing the filtrate by 3022g of 8% sodium bicarbonate aqueous solution for layering, distilling the organic layer to recover the solvent, adding 1380g of hexane into the concentrated residue, stirring for crystallization, filtering, drying the filter cake to obtain 1660g of p-acetoxyacetophenone with HPLC purity>99.9％。1H NMR(400MHz,(CD3)2SO):δ＝2.31(s,3H),2.59(s,3H),7.29(d,J＝8.8,2H),8.02(d,J＝8.8,2H)。13C NMR(100MHz,(CD3)2SO):δ＝21.34,27.18,122.58,128.99,134.89,154.59,169.31,197.36。
Example 2
Synthesis of p-acetoxyacetophenone:
390g of dichloromethane, 130g of p-hydroxyacetophenone and 116g of triethylamine are sequentially added into a 1000mL reaction bottle, stirring is started, and 108g of acetyl chloride is dropwise added under the temperature controlled at 30-40 ℃. After the dropwise addition, stirring was continued for 6 hours under heat preservation, 260g of water was added, and after stirring for 0.5 hour, the layers were separated. Adding 130g of water into the organic layer, adjusting the organic layer to be neutral by using sodium bicarbonate, distilling the layered organic layer to recover the solvent, adding 130g of hexane into the concentrated residue, stirring for crystallization, filtering, and drying the filter cake to obtain 150g of p-acetoxyacetophenone with the HPLC purity of 99.5%.
Example 3
Synthesis of 1- (4-acetoxyphenyl) ethanol:
2880g of toluene, 1440g of p-acetoxyacetophenone (obtained by the preparation of example 1) and 72g of Pd/C (water content: 50%, Pd 5% in dry basis) were put into a 5L pressure reactor, and were subjected to replacement with nitrogen and hydrogen in this order, then the internal temperature was controlled to 15-20 ℃ and the reaction was stirred under a hydrogen pressure of 8 bar. After the reaction, Pd/C was recovered by filtration, the solvent was recovered by distillation from the filtrate, and the concentrate was further distilled under reduced pressure to obtain 1440g of 1- (4-acetoxyphenyl) ethanol with an HPLC purity of 99.0%.1H NMR(400MHz,(CD3)2SO):δ＝1.32(d,J＝6.4,3H),2.25(s,3H),4.73(q,J＝6.4,1H),5.21(b,1H),7.05(d,J＝8.8,2H),7.37(d,J＝8.8,2H)。13C NMR(100MHz,(CD3)2SO):δ＝21.27,26.35,58.09,121.75,126.77,145.34,149.52,169.79。
Example 4
Synthesis of 1- (4-acetoxyphenyl) ethanol:
500g of methanol, 250g of p-acetoxyacetophenone (obtained by the preparation of example 1) and 12.5g of Raney nickel are put into a 1L pressure reaction kettle, and after nitrogen and hydrogen are sequentially substituted, the internal temperature is controlled to be 40-45 ℃, and the reaction is stirred under the hydrogen pressure of 8 bar. After the reaction, Raney nickel was recovered by filtration, the solvent was recovered by distillation from the filtrate, and the concentrate was further distilled under reduced pressure to give 240g of 1- (4-acetoxyphenyl) ethanol with HPLC purity of 98.6%.
Example 5
Synthesis of p-acetoxystyrene:
adding 1800g of DMAC (N, N-dimethylacetamide), 80g of NaOH, 360g of 1- (4-acetoxyphenyl) ethanol and 3.6g of p-tert-butylcatechol (TBC, polymerization inhibitor) into a 5L reaction kettle, and heating to 100-110 ℃ under stirring for reaction. After the reaction, the solvent was recovered by distillation under reduced pressure, 1440g of DCM (dichloromethane) was added to the residue, 1800g of water was added with stirring, the layers were separated, the solvent was recovered by short-steaming the organic layer, and the residue was distilled under reduced pressure with an oil pump to give 253g of p-acetoxystyrene with a GC purity of 98.4%.1H NMR(400MHz,(CD3)2SO):δ＝2.27(s,3H),5.26(dd,J＝0.8,10.8,1H),5.81(dd,J＝0.8,17.6,1H),6.74(dd,J＝10.8,17.6,1H),7.11(d,J＝8.8,2H),7.51(d,J＝8.8,2H)。13C NMR(100MHz,(CD3)2SO):δ＝21.28,114.80,122.44,127.59,135.26,136.20,150.59,169.61。
Example 6
Synthesis of p-acetoxystyrene:
4500g of DMAC (N, N-dimethylacetamide), 280g of KOH, 900g of 1- (4-acetoxyphenyl) ethanol and 9.0g of TBC are added into a 10L reaction kettle, and the temperature is raised to 100-110 ℃ under stirring for reaction. After the reaction, the solvent was recovered by distillation under reduced pressure, 3600g of DCM (dichloromethane) was added to the residue, 4500g of water was added with stirring, the layers were separated, the solvent was recovered by short-steaming the organic layer, the residue was distilled under reduced pressure with an oil pump to obtain 642g of p-acetoxystyrene with GC purity of 98.7%.
Example 7
Stability test of reaction solution for synthesizing p-acetoxystyrene:
the synthesis process as shown in example 5 was repeated, after the reaction was completed, the reaction mixture was not subjected to post-treatment, and heat stability was measured by further heating, and the concentration of the product in the mixture was followed by HPLC external standard method, and the results are shown in Table 1 below. The data in Table 1 show that p-acetoxystyrene exhibits good stability over the time tested in the reaction temperature range, which is sufficient to ensure the reaction is complete.
TABLE 1
Comparative example 1
Synthesis of p-acetoxystyrene:
a500 mL reaction flask was connected to a thermometer, a Kjeldahl head, and a vacuum system. 540.6g of 1- (4-acetoxyphenyl) ethanol, 27.0g of TBC and 5.4g of potassium bisulfate are added into a reaction flask, stirring is started, vacuum of 10mmHg is maintained, heating is carried out to 120-130 ℃, reaction is maintained for 1 hour, then the vacuum is further increased to 1mmHg, crude products are distilled off while reaction is carried out, 371g of crude products are collected, the GC purity is 90.3%, and 140g of residue is left in the reaction flask. 18.6g of TBC was added to the crude product and purified again by short steaming under reduced pressure to give 335g of p-acetoxystyrene with a GC purity of 98.8%.
Comparative example 2
Synthesis of p-acetoxystyrene:
a1000 mL reaction flask was connected to a thermometer, a Kjeldahl head, and a vacuum system. Adding 800g of 1- (4-acetoxyphenyl) ethanol, 40g of TBC and 8g of potassium bisulfate into a reaction flask, stirring, keeping vacuum of 10mmHg, heating to 120-130 ℃, keeping the reaction for 1 hour, further increasing the vacuum to 1mmHg, evaporating a crude product while reacting, collecting 447g of the crude product, wherein the GC purity is 88.7 percent, and the residue is 432 g. 16.5g of TBC was added to the crude product and purified again by short steaming under reduced pressure to give 388g of p-acetoxystyrene with a GC purity of 98.7%.
The specific comparison of the yields of example 5, example 6, comparative example 1 and comparative example 2 is shown in Table 2:
TABLE 2
Note: the yield is molar yield calculated according to the actual mass of the raw materials and the products, and the purity is not considered
From the table, the yield of the method is better than that of the method for dehydrating to alkene by acid catalysis, the product can stably exist in a reaction system, the yield change is not obvious after amplification, and the yield is sharply reduced in an acid catalysis elimination scheme.
In conclusion, the present invention effectively overcomes various disadvantages of the prior art and has high industrial utilization value.
The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.
Claims (10)
1. A method for preparing p-acetoxystyrene, comprising:
1) p-hydroxyacetophenone is reacted with an acetylation reagent to prepare p-acetoxyacetophenone, and the reaction equation is as follows:
2) the p-acetoxyacetophenone is hydrogenated and reduced to prepare the 1- (4-acetoxyphenyl) ethanol, and the reaction equation is as follows:
3) the p-acetoxystyrene is prepared by carrying out elimination reaction on 1- (4-acetoxyphenyl) ethanol, and the reaction equation is as follows:
2. the method for producing p-acetoxystyrene according to claim 1, wherein in the step 1), the reaction is carried out in the presence of an acid-binding agent;
and/or, in the step 1), the reaction is carried out in the presence of a solvent selected from organic solvents;
and/or in the step 1), the reaction temperature is 10-80 ℃;
and/or, in the step 1), the molar ratio of the p-hydroxyacetophenone to the acetylation reagent is 1: 1-2;
and/or, in the step 1), the acetylation reagent is one or more selected from acetyl chloride and acetic anhydride;
and/or, in the step 1), the post-treatment of the reaction comprises: solid-liquid separation and liquid-phase crystallization.
3. The method for preparing p-acetoxystyrene according to claim 2, wherein in step 1), the acid scavenger is selected from the group consisting of alkali;
and/or in the step 1), the molar ratio of the p-hydroxyacetophenone to the acid binding agent is 1: 1-5;
and/or, in the step 1), the solvent is selected from one or more of ester solvents, carbonate solvents, ketone solvents, ether solvents, halogenated alkane solvents and acetic acid;
and/or in the step 1), the reaction temperature is 20-50 ℃;
and/or, in the step 1), the molar ratio of the p-hydroxyacetophenone to the acetylation reagent is 1: 1.2 to 1.5.
4. The method for preparing p-acetoxystyrene according to claim 3, wherein in step 1), the acid scavenger is selected from organic base and/or inorganic base;
and/or in the step 1), the molar ratio of the p-hydroxyacetophenone to the acid binding agent is 1: 1.1 to 1.5.
5. The method for preparing p-acetoxystyrene according to claim 4, wherein in step 1), the organic base is selected from tertiary amine, preferably selected from one or more of triethylamine, tributylamine, diisopropylethylamine;
and/or, in the step 1), the inorganic base is selected from alkali metal carbonate, and the alkali metal carbonate is preferably selected from one or more of sodium carbonate and potassium carbonate.
6. The method for producing p-acetoxystyrene according to claim 1, wherein in the step 2), the reaction is carried out in the presence of a catalyst;
and/or, in the step 2), the reaction is carried out in the presence of a solvent, wherein the solvent is selected from organic solvents;
and/or in the step 2), the reaction temperature is 10-80 ℃;
and/or in the step 2), the reaction pressure is 3-15 bar;
and/or, in the step 2), the reaction is carried out in a reducing atmosphere;
and/or, in the step 2), the post-treatment of the reaction comprises: solid-liquid separation, desolventizing and purification.
7. The method for preparing p-acetoxystyrene according to claim 6, wherein in step 2), the catalyst is selected from one or more of palladium-carbon based catalyst, nickel based catalyst;
and/or, in the step 2), the solvent is selected from one or more of ester solvents, carbonate solvents, alcohol solvents and aromatic hydrocarbon solvents;
and/or in the step 2), the reaction temperature is 20-50 ℃;
and/or in the step 2), the reaction pressure is 5-10 bar;
and/or, in the step 2), the reducing atmosphere is selected from a hydrogen atmosphere.
8. The method for producing p-acetoxystyrene according to claim 1, wherein in the step 3), the reaction is carried out in the presence of a base;
and/or, in the step 3), the molar ratio of the 1- (4-acetoxyphenyl) ethanol to the base is 1: 0.8 to 5;
and/or, in the step 3), the reaction is carried out in the presence of a solvent selected from polar aprotic solvents;
and/or in the step 3), the reaction temperature is 80-150 ℃;
and/or, in the step 3), the post-treatment of the reaction comprises: desolventizing, washing with water, extracting with an organic solvent, desolventizing the organic phase, and purifying.
9. The method for producing acetoxystyrene according to claim 8, wherein in the step 3), the base is selected from inorganic bases;
and/or, in the step 3), the molar ratio of the 1- (4-acetoxyphenyl) ethanol to the base is 1: 1-3;
and/or, in the step 3), the solvent is selected from one or more of DMAC, DMF and NMP;
and/or in the step 3), the reaction temperature is 100-130 ℃.
10. The method of claim 9, wherein in step 3), the inorganic base is selected from one or more of hydroxides of alkali metals and hydroxides of alkaline earth metals, and is more preferably selected from one or more of NaOH, KOH and LiOH.
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| CN111777511A (en) * | 2020-08-07 | 2020-10-16 | 湖北顺明化工有限公司 | Production process of 4-acetoxystyrene |
| CN112694402A (en) * | 2020-12-28 | 2021-04-23 | 上海博栋化学科技有限公司 | Synthesis method of p-acetoxystyrene |
| CN116102422A (en) * | 2022-12-30 | 2023-05-12 | 安徽英特美科技有限公司 | A kind of preparation method of 4-acetoxystyrene |
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| CN112694402A (en) * | 2020-12-28 | 2021-04-23 | 上海博栋化学科技有限公司 | Synthesis method of p-acetoxystyrene |
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