JP2002179621A - Method for producing 4-acetoxystyrene - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an industrially advantageous method for producing 4- acetoxystyrene. SOLUTION: This method for producing 4-acetoxystyrene comprises subjecting a 4-acetoxyhalobenzene to Heck reaction, or subjecting 4-acetoxybenzaldehyde or 4-hydroxybenzaldehyde to Wittig reaction followed by optionally performing an acetylation.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing 4-acetoxystyrene.

[0002]

2. Description of the Related Art 4-acetoxystyrene is a known compound used as a pharmaceutical intermediate, a photo resist material, an adhesive, a coating material and the like. Methods for synthesizing 4-acetoxystyrene are known in the art,
It can be synthesized as follows by the Corson method (J. Org. Chem., 23, 544 (1958)). That is, 4-hydroxyacetophenone is reacted with acetic anhydride in an aqueous caustic alkali solution to form 4-acetoxyacetophenone, and then reduced with hydrogen gas in the presence of a palladium-carbon catalyst to obtain 4-acetoxyphenylmethylcarbinol, and hydrogen sulfate is obtained. Heat treatment is performed in the presence of a dehydration catalyst such as potassium to obtain 4-acetoxystyrene.

According to the above method, there is a problem that the dehydration yield of 4-acetoxyphenylmethylcarbinol is as low as 55%, and an improved method has been proposed. For example, Japanese Patent Laid-Open No. 4-2
In the method described in JP-A-44043, 4-acetoxyphenylmethylcarbinol is continuously or semi-continuously supplied to a reactor equipped with a dehydration catalyst and heat-treated. The raw water is distilled off, while the heavy substances are withdrawn from the reactor.
Although the yield of this method is slightly improved over that of the Corson method, the yield is still in the 70% range even under good conditions, and is not necessarily satisfactory. In addition, there is a difficult problem in operation such that the reaction performance is reduced unless the contents are constantly extracted from the reactor.

[0004]

SUMMARY OF THE INVENTION It is therefore an object of the present invention to provide an industrially advantageous process for producing 4-acetoxystyrene which has not been satisfactory with the conventional processes.

[0005]

Means for Solving the Problems The present inventors have made intensive studies to solve the conventional problems, and as a result, have reached the present invention. That is, the first aspect of the present invention provides a method for producing 4-acetoxystyrene represented by the following formula (2), wherein a 4-acetoxyhalobenzene represented by the following formula (1) is subjected to a Heck reaction. .

Further, the second invention comprises a first step of subjecting 4-hydroxybenzaldehyde represented by the following formula (1) to a Wittig reaction to obtain 4-vinylphenol represented by the following formula (2): A process of acetylating 4-vinylphenol represented by the formula (2) to obtain 4-acetoxystyrene represented by the following formula (3): provide.

Further, a third aspect of the present invention provides a first step of acetylating 4-hydroxybenzaldehyde represented by the following formula (1) to obtain 4-acetoxybenzaldehyde represented by the following formula (2): A 4-step for obtaining 4-acetoxystyrene represented by the following formula (3) by subjecting 4-acetoxybenzaldehyde represented by (2) to a Wittig reaction to obtain 4-acetoxystyrene. provide. According to the present invention, 4-acetoxystyrene can be produced safely on an industrial scale with excellent economic efficiency.

[0008]

Next, the present invention will be described in more detail with reference to preferred embodiments. First invention: 4-acetoxyhalobenzene used in the present invention is synthesized from 4-halophenol, and 4-halophenol is not particularly limited.
That is, examples of 4-halophenol include 4-fluorophenol, 4-chlorophenol, 4-bromophenol, and 4-iodophenol. The 4-acetoxyhalobenzene used in the present invention is 4
-It can be easily synthesized by reacting halophenol with acetic anhydride in the presence of amidosulfuric acid.

In the Heck reaction of the present invention, the following catalyst is used. The palladium-based catalyst used in the present invention is a palladium halide (I) such as palladium (II) chloride, palladium (II) bromide, or palladium (II) iodide.
Organic acids such as palladium (II), palladium (II) acetate and palladium (II) propionate, palladium (I
I) acetylacetonate, palladium cyanide (I
And divalent palladium compounds such as I), palladium (II) nitrate and palladium (II) sulfate. The amount of the palladium catalyst used is 0.001 to 10 mol%, preferably 0.001 mol%, based on 4-acetoxyhalobenzene.
5 to 2 mol%. If the amount of the catalyst is too small, the yield decreases, while if it is too large, the palladium catalyst is expensive, so that the present invention is not economically feasible.

The phosphine ligand used in the present invention is a triarylphosphine such as triphenylphosphine, tri-o-tolylphosphine, tri-m-tolylphosphine, tri-p-tolylphosphine, diphenyl-p-tolylphosphine and the like. Alkylarylphosphines such as diethylphenylphosphine, ethyldiphenylphosphine, dimethylphenylphosphine and methyldiphenylphosphine; trialkylphosphines such as tributylphosphine and triethylphosphine;
Bidentate phosphines such as -bis (diphenylphosphino) ethane, 1,3-bis (diphenylphosphino) propane, and 1,4-bis (diphenylphosphino) butane; In what we can do,
Triphenylphosphine, tolylphosphine and the like are preferred. The phosphine ligand is used such that the phosphorus / palladium (atomic ratio) is in the range of 1 to 50, preferably 1 to 10.

The reaction solvent used in the present invention may be an ether solvent, an oxygen-containing solvent, a nitrogen-containing solvent, an aromatic hydrocarbon solvent, an aliphatic hydrocarbon solvent, an organic halogen solvent, etc. Can be mentioned, but acetonitrile or a mixed solvent containing acetonitrile is particularly preferable in terms of the reaction results.

In the present reaction, a base substance for immediately neutralizing hydrogen halide generated in the system during the reaction is present. Examples of the base substance used include trimethylamine, triethylamine, tributylamine, diethylamine, pyridine, organic bases such as DBU (1,8-diazabicyclo [5.4.0] undecene-7), and strongly basic ion exchange resins. Among them, trialkylamines such as triethylamine and tributylamine are more preferable.

The method of the present invention is performed in an atmosphere of ethylene gas, and the pressure of ethylene gas is higher than normal pressure.
0.3-3MP in consideration of reactivity and equipment problems
The pressure of a is preferred. In addition, the method of the present invention may be carried out at 0 ° C to 2 ° C.
Although it is carried out at 00 ° C., it is preferred to carry out at a temperature of 170 ° C. or less in consideration of the thermal stability of 4-acetoxystyrene.

After the completion of the reaction, the hydrogen halide of the organic base in the reaction solution cooled to room temperature is filtered off, and the residue is washed with the same composition as the solvent. Next, the filtrate and the washing solution were combined, and the solvent was distilled off under reduced pressure.
Add a water-immiscible solvent to dissolve. The precipitated crystals are separated by filtration, and the filtrate is washed with an aqueous ammonium chloride solution and then with water. The organic phase is dried over anhydrous sodium sulfate, and a polymerization inhibitor such as tertiary butyl catechol is added thereto and distilled to obtain the desired 4-acetoxystyrene.

Second invention: In the present invention, the Wittig reagent to be reacted with 4-hydroxybenzaldehyde is generated in a reaction system from methyltriphenylphosphonium halide and a strong base. Methyltriphosphonium halide is prepared from triphenylphosphine and methyl halide. As methyl halide, methyl chloride, methyl bromide, and methyl iodide can be used, but in view of economy, methyltriphenylphosphonium chloride or methyltriphenylphosphonium bromide is preferable.

Strong bases include alcoholates such as sodium methoxide, sodium ethoxide, potassium tert-butoxide, 1,8-diazabicyclo [5.4.0] undecene-7 (DBU), 1,5-diazabicyclo [4 .
3.0] non-5-ene (DBN), tertiary amines such as 1,4-diazabicyclo [2.2.2] octane (DABCO), and organometallic compounds such as phenyllithium and methyllithium. In consideration of economy, it is preferable to use alkoxides such as sodium methoxide and sodium ethoxide. In preparing the Wittig reagent, 1 to 5 moles, preferably 1.1 to 2 moles of a strong base is used per 1 mole of methyltriphosphonium halide.

The Wittig reagent is used in an amount of 1 to 3 mol, preferably 1.05 to 1.5 mol, per 1 mol of 4-hydroxybenzaldehyde used in the present invention. The solvent used in this reaction is N, N-dimethylformamide (DMF), N, N-diethylacetamide (DM
A), aprotic polar solvents such as dimethylsulfoxide (DMSO), hexamethylphosphoric triamide (HMPA), acetonitrile, tetrahydrofuran (THF), dioxane and dimethoxyethane are used, but from the viewpoint of reactivity and economy. In particular, it is desirable to use DMF, DMA or THF.

The reaction temperature in this reaction is 70 ° C. or less,
Desirably, it is 0 to 30 ° C. The reaction time is from 0 to 5 hours, preferably from 30 minutes to 2 hours from the moment when the predetermined amount of 4-acetoxybenzaldehyde and the Wittig reagent are mixed.

The 4-vinylphenol obtained by the Wittig reaction can be acetylated according to a conventional method, but a particularly preferred method is acetylation using amide sulfuric acid as a catalyst and acetic anhydride. More specifically, acetic anhydride is used in an amount of 1 to 10 mol, preferably 1 to 3 mol, in the presence of 0.01 to 1 mol, preferably 0.1 to 0.4 mol, of amidosulfuric acid per 1 mol of 4-vinylphenol. The reaction is carried out at a temperature of 30 to 120C, preferably 50 to 90C, for 10 minutes to 5 hours, preferably 20 minutes to 2 hours. The amidosulfuric acid can be reused after being filtered off from the reaction solution.

After completion of the reaction, the reaction solution is poured into water, and the precipitated phosphine oxide is separated by filtration. The phosphine oxide is washed with water, the washing solution and the reaction filtrate are combined, and this is washed with toluene. Subsequently, the aqueous solution was acidified according to a conventional method to obtain 4
Liberate the vinylphenol and extract into an organic solvent such as ethyl acetate. The organic phase is washed with saturated sodium sulfate and then dried over anhydrous sodium sulfate. The sodium sulfate is separated by filtration and the solvent is distilled off under reduced pressure to obtain 4-vinylphenol. The obtained 4-vinylphenol is acetylated according to a conventional method. An organic solvent such as ethyl acetate is added to the reaction solution to extract the desired 4-acetoxystyrene, and the organic phase is washed with water and dried. By doing so, 4-acetoxystyrene is obtained.

Third invention: The present invention is an invention in which the reaction order in the second invention is changed, and the first step comprises 4 steps.
-Hydroxybenzaldehyde acetylation to obtain 4-acetoxybenzaldehyde, and reacting the 4-acetoxybenzaldehyde with a Wittig reagent to obtain a target substance, 4-acetoxystyrene.

The production of 4-acetoxystyrene using the above 4-acetoxybenzaldehyde is carried out by the following method. First, a methyltriphenylphosphonium halide as described above is dissolved in a solvent and charged into a reactor, and then a solution in which the strong base is dissolved or dispersed in the same solvent is added to prepare a Wittig reagent. Subsequently, a solution prepared by dissolving 4-acetoxybenzaldehyde in the same solvent is added for a predetermined time in the same manner as described above, and the reaction is performed at a predetermined temperature. Thereafter, 4-acetoxystyrene is obtained in the same manner as in the second invention.
The second invention and the third invention are superior to the second invention in terms of the reaction yield.

[0023]

The present invention will be described in more detail with reference to the following examples, which should not be construed as limiting the invention thereto. First invention: Example 1 200 ml with stirrer, thermometer and pressure gauge
4-Acetoxybromobenzene in autoclave
5 g (0.1 mol), 0.113 g of palladium acetate
(0.5 mmol), tri-o-tolylphosphine3.
8 g (12.5 mmol), 20 g of triethylamine
(0.196 mol) and 25 g of acetonitrile were charged, the system was replaced with ethylene gas, and the mixture was reacted at 90 ° C. for 30 minutes with stirring under a pressure of 1 MPa.

When the absorption of ethylene has ceased, the reaction solution is taken out, the precipitate is filtered off, and the filtration residue is washed with acetonitrile 2
Wash with 5 g. The filtrate and the washing solution are combined, the solvent is distilled off under reduced pressure, and the concentrate is dissolved by adding 100 ml of ethyl acetate. The precipitated crystals are filtered off, and the filtrate is washed with 100 ml of a 5% ammonium chloride aqueous solution and then with 100 ml of water. The organic phase was dried over anhydrous sodium sulfate, tertiary butyl catechol was added thereto, and the mixture was distilled under reduced pressure to give 14.8 g of 4-acetoxystyrene (yield: 91.0 g).
3%). The product was found to have a mass number of 162 by gas chromatography / mass spectrometry and an elemental analysis value of C: 7
4.1% (74.0%), H: 6.2% (6.2%),
O: Identified from 19.7% (19.8%) (calculated values in parentheses).

Example 2 The procedure of Example 1 was repeated, except that 22.6 mg (0.1 mmol) of palladium acetate was used. 14.6 g of 4-acetoxystyrene (yield: 90.1%) I got

Example 3 The procedure of Example 1 was repeated, except that tri-m-tolylphosphine was used instead of tri-o-tolylphosphine, to give 14.4 g of 4-acetoxystyrene (yield: 88.8%).

Example 4 The procedure of Example 1 was repeated, except that 0.8 g (2 mmol) of 1,2-bis (diphenylphosphino) ethane was used instead of tri-o-tolylphosphine. , 4-acetoxystyrene 13.8 g (Yield: 85.
2%).

Example 5 The same procedure as in Example 1 was carried out except that the pressure of ethylene gas was changed to 2 MPa, and 4-acetoxystyrene 1
5.2 g (yield: 93.8%) was obtained.

Example 6 The procedure of Example 1 was repeated except that the reaction temperature was changed to 120 ° C., to obtain 13.0 g of 4-acetoxystyrene (yield: 80.0%).

Example 7 36.3 g (0.19 g) of tributylamine as an organic base
6 mol) was used in the same manner as in Example 1 except that 14.7 g of 4-acetoxystyrene (yield: 9) was used.
0.7%).

Example 8 The procedure of Example 1 was repeated, except that tetrahydrofuran was used as a solvent, to obtain 14.5 g of 4-acetoxystyrene (yield: 89.6%).

Second Invention: Example 1 Production of 4-vinylphenol: 92.9 g (0.26 mol) of methyltriphenylphosphonium bromide in a 500 ml flask equipped with a stirrer, a thermometer, and a dropping funnel.
And 170 ml of DMF. Subsequently, 24.3 g (0.45 mol) of sodium methoxide was added to DMF56.
What was prepared in a dropping funnel was dispersed in
Add while keeping the liquid temperature in the flask at 15-20 ° C
Wittig reagent was prepared. At the same temperature, 24.4 g (0.2 mol) of 4-hydroxybenzaldehyde was added to DM
F30ml dissolved in dropping funnel about 3
Added over 0 minutes. After completion of the dropwise addition, the liquid temperature was raised to 25 ° C., and the reaction was further performed for 1 hour.

After the completion of the reaction, the reaction solution was poured into 1 liter of water while stirring. The precipitated solid was separated by filtration, and the cake was washed with 200 ml of water. The filtrate and washings were collected and washed twice with 300 ml of toluene. Carbon dioxide is blown into the aqueous solution to release 4-vinylphenol, and ethyl acetate 5
Extracted with 00 ml. The organic phase was washed twice with 200 ml of a saturated aqueous sodium sulfate solution and dried over anhydrous sodium sulfate. The sodium sulfate was filtered off, and the ethyl acetate was distilled off to obtain 4
-23.4 g of vinylphenol (yield 97.0%) was obtained.

Production of 4-acetoxystyrene: stirrer,
In a 100 ml flask equipped with a reflux tube and a thermometer,
23.4 g (0.194 mol) of 4-vinylphenol,
39.6 g (0.388 mol) of acetic anhydride and 3.8 g (0.039 mol) of amidosulfuric acid were charged, and 3
The reaction was performed for 0 minutes. The reaction solution was allowed to cool to room temperature, and the precipitated amidosulfuric acid was separated by filtration and washed with 7 g of acetic anhydride. The combined filtrate and washings were distilled under reduced pressure to give 4-acetoxystyrene 2
6.7 g (85.0% yield) was obtained.

Example 2 The procedure of Example 1 was repeated, except that 81.3 g (0.26 mol) of methyltriphenylphosphonium chloride was used instead of methyltriphenylphosphonium bromide. 27.0 g of styrene (yield 85.9)
%).

Example 3 Instead of sodium methoxide, 68.5 g of 1,8-diazabicyclo [5.4.0] undecene-7 (0.
Except for using 45 mol), the same procedure as in Example 1 was carried out to obtain 25.3 g of 4-acetoxystyrene (yield: 8).
0.5%).

Example 4 Example 1 was repeated except that 28.8 g of n-butyllithium (0.45 mol) was used instead of sodium methoxide, and tetrahydrofuran was used as a reaction solvent.
And 4-acetoxystyrene.
6 g (84.6% yield) was obtained.

Example 5 500 ml equipped with a stirrer, a thermometer, and a dropping funnel
A flask was charged with 21.9 g (0.183 mol) of 4-vinylphenol obtained in the same manner as in Example 1, 1.9 M
200 ml of aqueous sodium hydroxide solution was charged and the liquid temperature was adjusted to 1
While maintaining the temperature at 0 to 15 ° C, 24.9 g of acetic anhydride (0.
268 mol) was added dropwise over 2 hours. After dropping, 2
After further reacting at 5 ° C. for 30 minutes, the mixture was extracted with 150 ml of ethyl acetate, the organic phase was washed with water, dried over anhydrous sodium sulfate, and distilled under reduced pressure to give 25.4 g of 4-acetoxystyrene.
(80.8% yield).

[0039]

According to the present invention as described above, it is possible to solve the conventional problems and to produce 4-acetoxystyrene by a safe method with excellent economic efficiency on an industrial scale.

 ────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Ryo Kitahara 3-35-7 F-Bigaoka Nishi, Aoba-ku, Yokohama-shi, Kanagawa 4F006 AA02 AC23 AC24 AC90 BA02 BA03 BA25 BA32 BA44 BA48 BA51 BA53 BB20 BB21 BB22 BB25 BC10 BC11 BC34 BE55 BJ50 BT16 4H039 CA21 CA66 CD20 CD40

Claims (14)

[Claims] 1. A method for producing 4-acetoxystyrene represented by the following formula (2), wherein a 4-acetoxyhalobenzene represented by the following formula (1) is subjected to a Heck reaction. 2. The method according to claim 1, wherein the palladium catalyst is used at 0.001 to 10 mol% of 4-acetoxyhalobenzene, and the phosphine ligand is used at a phosphorus / palladium (atomic ratio) of 1 to 50. Production method. 3. The method according to claim 1, wherein acetonitrile or a mixed solvent containing acetonitrile is used as the reaction solvent. 4. The method according to claim 1, wherein a trialkylamine is present in the reaction system. 5. The reaction is carried out in an ethylene gas atmosphere at a temperature of 0.3%.
The method according to claim 1, wherein the method is performed under a pressure of ３3 MPa. 6. The method according to claim 1, wherein the reaction is carried out at a temperature of 170 ° C. or lower. 7. A first step of subjecting a 4-hydroxybenzaldehyde represented by the following formula (1) to a Wittig reaction to obtain 4-vinylphenol represented by the following formula (2), and a first step represented by the following formula (2): Acetylating 4-vinylphenol to obtain 4-acetoxystyrene represented by the following formula (3): 8. The production method according to claim 7, wherein the Wittig reagent is generated in a reaction system from methyltriphenylphosphonium halide and a strong base. 9. The process according to claim 7, wherein the methyltriphenylphosphonium halide is methyltriphenylphosphonium chloride or methyltriphenylphosphonium bromide. 10. The method according to claim 8, wherein the strong base is sodium methoxide or sodium ethoxide. 11. The method according to claim 7, wherein 1 to 3 mol of a Wittig reagent is used per 1 mol of 4-hydroxybenzaldehyde. 12. The method according to claim 7, wherein N, N-dimethylformamide, N, N-diethylacetamide or tetrahydrofuran is used as the solvent. 13. The method according to claim 7, wherein 4-vinylphenol obtained by the Wittig reaction is acetylated using acetic anhydride with amide sulfuric acid as a catalyst. 14. A first step of acetylating 4-hydroxybenzaldehyde represented by the following formula (1) to obtain 4-acetoxybenzaldehyde represented by the following formula (2), and represented by the following formula (2): Wittig reaction of 4-acetoxybenzaldehyde is performed to give 4-acetoxybenzaldehyde represented by the following formula (3).
A method for producing 4-acetoxystyrene, comprising a second step of obtaining acetoxystyrene.