WO2015133525A1 - Guaiacyl vinyl ketone production method - Google Patents

Guaiacyl vinyl ketone production method Download PDF

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WO2015133525A1
WO2015133525A1 PCT/JP2015/056366 JP2015056366W WO2015133525A1 WO 2015133525 A1 WO2015133525 A1 WO 2015133525A1 JP 2015056366 W JP2015056366 W JP 2015056366W WO 2015133525 A1 WO2015133525 A1 WO 2015133525A1
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vinyl ketone
hydroxy
guaiacyl
methoxyphenyl
propanone
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PCT/JP2015/056366
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French (fr)
Japanese (ja)
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長谷川　良一
ゆかり 大田
勇二 秦田
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国立研究開発法人海洋研究開発機構
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups

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  • the present invention relates to a process for producing guaiacyl vinyl ketone (1- (4-hydroxy-3-methoxyphenyl) -2-propen-1-one).
  • Guayacyl vinyl ketone (1- (4-hydroxy-3-methoxyphenyl) -2-propen-1-one) has a polymerizable vinyl group and is useful as a monomer component in the synthesis of polymers. It is a serious substance. Further, since it contains a carbonyl group in the molecule, it is a compound that can be expected to have characteristics such as photosensitivity.
  • Patent Document 1 As a method for producing 4-hydroxyphenyl vinyl ketone having a structure different from that of guaiacyl vinyl ketone, a Lewis acid such as aluminum chloride is used starting from 3-chloro-1- (4-methoxyphenyl) -1-propanone. It is described in the following Patent Document 1 (the description of this document is incorporated herein by reference) that 4-hydroxyphenyl vinyl ketone can be obtained via the dehydrochlorination reaction used. Patent Document 1 describes that when a basic substance is used instead of Lewis acid, the reaction does not proceed smoothly.
  • Non-Patent Document 1 guaiacyl vinyl ketone is obtained.
  • this method is unsuitable as a method for producing guaiacyl vinyl ketone on an industrial scale in that a high-boiling solvent that must be reacted at a high temperature and difficult to recover after the reaction is used. Further, there is a problem that the yield is as low as 24% and the reaction efficiency is very low.
  • Patent Document 1 and Non-Patent Document 2 which are methods for producing the same phenyl vinyl ketone compound as guaiacyl vinyl ketone.
  • the methods described in Patent Document 1 and Non-Patent Document 2 use 3-chloro-1- (4-methoxyphenyl) -1-propanone or 3-chloro-1- (4-hydroxyphenyl) -2-methyl as a starting material.
  • a method for producing 4-hydroxyphenyl vinyl ketone or a derivative thereof using propan-1-one have opposite reaction conditions, and one document describes that the reaction does not proceed smoothly under the reaction conditions described in the other document.
  • the target product may not be obtained if the reaction conditions are different. It is difficult to analogize the system.
  • the reaction conditions using the basic substance described in Non-Patent Document 2 overlap with the conditions in which ⁇ -hydrogen of the carbonyl group is eliminated to proceed to the aldol reaction and Michael addition reaction conditions, and the generated vinyl ketones react. Since there is a possibility that an addition reaction or a polymerization reaction may occur, it is very difficult to predict that a desired object will be obtained depending on reaction conditions using a basic substance.
  • the present invention provides a method for producing guaiacyl vinyl ketone having a high reaction efficiency and suitable for production on an industrial scale as compared with the method described in Non-Patent Document 1. Was the problem to be solved.
  • the halogen atom is a chlorine atom or a bromine atom.
  • the solvent is an alcohol or water.
  • the basic substance is a basic substance selected from the group consisting of alkali metal hydroxides, alkali metal carbonates, alkali metal bicarbonates, and alkali metal alkoxides. is there.
  • the solvent is water
  • the basic substance is selected from the group consisting of alkali metal hydroxides, alkali metal carbonates, and alkali metal bicarbonates. It is a sex substance.
  • guaiacyl vinyl ketone According to the production method of the present invention, recovery from 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone under mild conditions compared to the method described in Non-Patent Document 1.
  • guaiacyl vinyl ketone can be produced with good yield using a simple solvent or a general-purpose basic substance. Therefore, according to the production method of the present invention, it is possible to produce guaiacyl vinyl ketone on an industrial scale.
  • FIG. 1 is a photograph of the polymer film obtained in Reference Example 1.
  • the method for producing the guaiacyl vinyl ketone of the present invention comprises the following general formula (1) in a solvent.
  • (1) In the formula, X represents a halogen atom.
  • 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone has a halogen atom added to the 3-position carbon atom of the propanone skeleton as shown in the general formula (1) above.
  • the 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is not particularly limited as long as it has the structural formula represented by the general formula (1).
  • the atoms can be fluorine atoms, chlorine atoms, bromine atoms, iodine atoms and the like, preferably chlorine atoms and bromine atoms.
  • the method for obtaining 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is not particularly limited.
  • 3-hydroxy-1- (4-hydroxy-3-methoxyphenyl) -1- Can be manufactured from propanone.
  • 3-hydroxy-1- (4-hydroxyphenyl) -2-methyl-propan-1-one described in Non-Patent Document 2 is heated in concentrated hydrochloric acid to give 3-chloro-1
  • 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is obtained.
  • 3-hydroxy-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is used in an aqueous solution of hydrohalic acid of 30 to 50% by mass, about 20 times by mass, in an amount of 40 to 90%.
  • hydrohalic acid used at this time is not particularly limited, and examples thereof include hydrochloric acid, hydrobromic acid, hydrofluoric acid, hydroiodic acid, and the like, preferably hydrochloric acid and hydrobromic acid.
  • a preferred embodiment of 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is 3-chloro-1- (4-hydroxy-3-methoxyphenyl) from the viewpoint of operability and safety.
  • the amount of 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is not particularly limited as long as it can be mixed in the system. It can be 1% (W / V) to 50% (W / V), preferably 1% (W / V) to 10% (W / V).
  • the solvent used in the production method of the present invention is not particularly limited as long as it is soluble in 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone.
  • water methanol Alcohols such as ethanol, isopropanol and butanol; ethers such as diethyl ether, tetrahydrofuran, dioxane and glyme; hydrocarbons such as benzene, toluene, xylene, hexane and cyclohexane; halogenated hydrocarbons such as chloroform, dichloromethane and chlorobenzene Ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone; aprotic polar solvents such as dimethylformamide, dimethylimidazolidinone, and dimethyl sulfoxide; esters such as ethyl acetate and butyl acetate Although s and the
  • the amount of the solvent used can be appropriately changed according to the amount of 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone, and is not particularly limited.
  • 3-halogeno-1- The amount of (4-hydroxy-3-methoxyphenyl) -1-propanone flowing is 1 to 100 times the mass of 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone. 3 to 50 times by mass is preferable.
  • the basic substance to be used is not particularly limited as long as the solvent contributes to becoming basic (alkaline).
  • alkali metal hydroxides alkali metal carbonates, alkali metals
  • the bicarbonates and alkali metal alkoxides are easy to dispose of. For reasons such as that it can be suitably used.
  • These basic substances may be used alone or in combination of two or more.
  • the production method of the present invention is economical. Further, since the solution becomes strongly basic and can react in a homogeneous system, it has an advantage that it is simple and the method of reducing the waste solution is reduced.
  • the amount of the basic substance used can be appropriately changed depending on the kind of the basic substance, the amount of 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone or the solvent used, and is not particularly limited. , 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone in an amount capable of neutralizing hydrohalic acid, preferably 0.85 equivalent of the hydrohalic acid -5.0 equivalents, more preferably 1.0-3.0 equivalents.
  • the means for contacting 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone with a basic substance is obtained by using 3-halogeno-1- (4-hydroxy-3-methoxyphenyl)-in a solvent.
  • 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is added to a container to which a predetermined amount of solvent is added. While adding an appropriate amount and stirring, 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is dissolved or diffused in a solvent, and then a basic substance is gradually added. preferable.
  • guaiacyl vinyl ketone is produced.
  • Conditions such as temperature and time during the reaction are not particularly limited, and are, for example, 0 ° C. to 100 ° C., preferably 15 ° C. to 80 ° C., and more preferably around room temperature.
  • the temperature is preferably 10 ° C to 40 ° C.
  • the reaction time can be appropriately set depending on the nature of the solvent and basic substance, the reaction temperature, and the like. For example, it is about 0.5 to 5.0 hours, preferably about 1.0 to 3.0 hours. It is.
  • the end point of the reaction is a method for detecting 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone or guaiacyl vinyl ketone, such as HPLC or thin layer chromatograph under the conditions described in Example 1. Thus, it can be determined by confirming the disappearance of the raw material compound and the production amount of the product.
  • 3-halogen-1-one obtained by reacting 3-hydroxy-1- (4-hydroxy-3-methoxyphenyl) -1-propanone with an aqueous hydrohalic acid solution.
  • 3-halogeno- obtained by extracting (4-hydroxy-3-methoxyphenyl) -1-propanone with an organic solvent incompatible with an aqueous hydrohalic acid solution and then adding a basic substance to the organic solvent, 3-halogeno- This can be achieved by bringing 1- (4-hydroxy-3-methoxyphenyl) -1-propanone into contact with a basic substance.
  • the organic solvent incompatible with the hydrohalic acid aqueous solution is not particularly limited as long as it is an organic solvent in which 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone can be dissolved.
  • Hydrocarbons such as benzene, toluene, xylene, hexane and cyclohexane; halogenated hydrocarbons such as chloroform, dichloromethane and chlorobenzene; esters such as ethyl acetate and butyl acetate; ketones such as methyl ethyl ketone and methyl isobutyl ketone;
  • the solvent etc. which are used for the manufacturing method of this invention which were made can be mentioned, These may be used individually or in mixture of 2 or more types.
  • guaiacyl vinyl ketone is obtained by contacting 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone with a basic substance in a solvent.
  • Guayacyl vinyl ketone is 1- (4-hydroxy-3-methoxyphenyl) -2-propen-1-one represented by the following formula (2), and has a vinyl group that is a polymerizable functional group. It is a useful substance that can be used as a monomer component of molecular materials.
  • Guaacyl vinyl ketone is in the form of an oil that is insoluble in water near neutrality. Therefore, after completion of the reaction, as a two-phase system of water and an organic solvent incompatible with water, guaiacyl vinyl ketone is transferred to the organic solvent layer, and salts generated as a result of the reaction are transferred to the aqueous layer. It is preferable to separate the target substance, guaiacyl vinyl ketone, and the substance soluble in water by transferring the substance.
  • the acid used for neutralization is not particularly limited as long as it can neutralize the basic substance in the reaction mixture.
  • hydrochloric acid, sulfuric acid, hydrobromic acid, phosphoric acid, acetic acid and the like can be used.
  • the liquidity of the aqueous layer after neutralization is preferably set to 3.0 to 9.0 as pH.
  • the organic solvent incompatible with the extraction water used in this case is not particularly limited as long as guaiacyl vinyl ketone can be dissolved, but for example, benzene, toluene, xylene, hexane, cyclohexane, etc.
  • Hydrocarbons such as chloroform, dichloromethane and chlorobenzene
  • esters such as ethyl acetate and butyl acetate
  • ketones such as methyl ethyl ketone and methyl isobutyl ketone
  • alcohols such as butanol and hexanol.
  • the method for obtaining guaiacyl vinyl ketone from the organic solvent layer containing guaiacyl vinyl ketone is not particularly limited. For example, by removing the organic solvent from the organic solvent layer under normal pressure or reduced pressure, guaiacyl vinyl ketone is obtained. It can be obtained as a colorless to slightly brown liquid.
  • the amount of water, acid, and the organic solvent that is incompatible with water is not particularly limited and can be appropriately set by those skilled in the art. Further, in order to increase the yield of guaiacyl vinyl ketone, the operation of adding an organic solvent incompatible with water to the aqueous layer separated during extraction and repeating the extraction one or more times is repeated. Also good. Furthermore, in order to obtain high-purity guaiacyl vinyl ketone, the organic solvent layer after extraction may be washed one or more times with water or the like.
  • the guaiacyl vinyl ketone is 90% or more, preferably 95%, by appropriately setting the conditions such as the content of each component, the combination of basic substance and solvent, pH of the solution, reaction temperature and time. % Or higher purity can be obtained. Therefore, the guaiacyl vinyl ketone obtained by the production method of the present invention can be used as a monomer component for producing a polymer compound as it is without undergoing a subsequent purification operation.
  • the guaiacyl vinyl ketone obtained by the production method of the present invention as described in Example 1, which will be described later, is added to silica gel or reverse phase. What is necessary is just to use for the means which refine
  • the resulting solution with the basic substance added is reacted by stirring at 10-80 ° C. for several minutes to several hours.
  • water and an acid were gradually added dropwise to the solution after the reaction to adjust the pH to 3.0 to 9.
  • an organic solvent incompatible with water is added to extract and separate guaiacyl vinyl ketone.
  • the aqueous layer is re-extracted using the organic solvent. Repeat this one or more times.
  • the obtained extracts (organic solvent layer) are combined and washed with water. From the washed extract, the organic solvent is distilled off under reduced pressure or low temperature to obtain guaiacyl vinyl ketone.
  • the guaiacyl vinyl ketone obtained by the production method of the present invention has a vinyl group which is a polymerizable functional group, it can be used as a monomer component when producing a polymer substance. For example, as shown in FIG. In addition, it can be polymerized alone or together with a crosslinking agent or other monomer component. Furthermore, guaiacyl vinyl ketone is useful as a raw material for producing a photosensitive composition such as a resist.
  • Example 1 In a 100 ml Erlenmeyer flask to which 20 ml of ethanol was added, 1.41 g (0.0066 mol) of 3-chloro-1- (4-hydroxy-3-methoxyphenyl) -1-propanone was dissolved at room temperature with stirring. . To this solution, 0.9 g (0.0132 mol) of sodium ethoxide was added at room temperature and reacted for 1.5 hours to obtain guaiacyl vinyl ketone.
  • the raw material 3-chloro-1- (4-hydroxy-3-methoxyphenyl) -1-propanone was detected with a retention time of 9.9 minutes, and the target guaiacyl vinyl ketone was detected with a retention time of 8 minutes. Detected at 9 minutes. After completion of the reaction, the peak of the retention time of 9.9 minutes, which is the peak of the raw material, disappeared.
  • HPLC conditions Apparatus: Waters 2795, 2998 Column: X-bridge C18, 3.5 ⁇ , diameter 4.6 mm ⁇ 100 mm, (30 ° C.) Carrier: (A) 2 mM-NH 4 OAc aq. (0.05% V / V Formula acid), (B) MeOH Gradient: 5% V / V MeOH (1 min), MeOH 5% V / V ⁇ 95% V / V (1-15 min), 95% V / V MeOH (15-18 min) Detector: UV300nm
  • the total amount of crude guaiacyl vinyl ketone was purified by column treatment as follows. Wako Gel C200 was packed 100 mm in a glass column having an inner diameter of 21 mm, and toluene was supplied. After the filler was filled with toluene, crude guaiacyl vinyl ketone was dissolved in 6 ml of toluene and supplied. Toluene was used as a solvent, and 20 ml fractions were collected. The fraction containing the desired product was confirmed by thin-layer chromatography and collected, and then toluene was distilled off under reduced pressure by an evaporator to obtain 0.75 g of purified guaiacyl vinyl ketone. The purification yield was 61% and the HPLC purity was 99%.
  • the obtained purified guaiacyl vinyl ketone was subjected to reversed-phase UPLC-time-of-flight accurate mass spectrometry (ACCUITY UPLC H-Class, XevoG2 QTOF; manufactured by Waters) under the following conditions, and the mass spectrum was measured. Negative ions were detected. This corresponds to the molecular weight of the target product-1.
  • Reversed phase UPLC condition column ACQUITY UPLC HSS T3 C18 Column, 1.8 ⁇ m, 2.1 mm ⁇ 100 mm (manufactured by Waters), Eluent: (A) [2 mM ammonium acetate, 0.05% V / V formic acid], (B) methanol, Solution: Eluent (B) 0-5 minutes 5% V / V-95% V / V; Eluent (B) 5-7 minutes 95% V / V, Column temperature: 40 ° C., flow rate: 0.4 ml / min
  • Example 2 In a 50 ml Erlenmeyer flask containing 25 ml of water, 0.61 g (0.00284 mol) of 3-chloro-1- (4-hydroxy-3-methoxyphenyl) -1-propanone was dissolved with stirring at room temperature. . To this solution, 5.69 g (0.00569 mol) of 1M NaOH aqueous solution was gradually added at room temperature to obtain a yellow uniform reaction solution. This reaction solution was reacted at room temperature for 0.5 hour and at 65 ° C. for 1 hour. The disappearance of the peak of the raw material was confirmed by HPLC carried out under the conditions described in Example 1.
  • reaction solution was cooled to room temperature and further neutralized with 1.06 g (0.00290 mol) of 10% (W / W) hydrochloric acid to adjust the pH to about 5.
  • a brown oil separated.
  • 10 ml of ethyl acetate was added and transferred to a separating funnel having a capacity of 50 ml, and an ethyl acetate layer was collected. Further, the aqueous layer was extracted with 10 ml of ethyl acetate and extracted twice in total. The extract was washed with 5 ml of water, and volatile components were distilled off from the ethyl acetate layer under reduced pressure using an evaporator.
  • This white powder was dissolved in methanol, tetrahydrofuran, acetone, etc., but not in chloroform. This powder was placed in a test tube as a tetrahydrofuran solution, and the solvent was distilled off to form a transparent film (see FIG. 1). Further, this transparent film could be dissolved in a dilute caustic soda aqueous solution.
  • the white powder polymer was dissolved in an alkaline aqueous solution, neutralized with an acidic substance such as hydrochloric acid, precipitated, and washed with filtered water to obtain a purified product.
  • the production method of the present invention comprises 3-halogen-1- (4-hydroxy-3) from 3-hydroxy-1- (4-hydroxy-3-methoxyphenyl) -1-propanone obtained by microbial degradation of lignin and the like. It is an efficient method for producing high-purity guaiacyl vinyl ketone on an industrial scale via -methoxyphenyl) -1-propanone. Guaacyl vinyl ketone can be used as a monomer component in producing a polymer, and is further useful as a raw material for producing a photosensitive composition such as a resist. Therefore, the production method of the present invention is a method that enables production of industrially useful guaiacyl vinyl ketone on an industrial scale.

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Abstract

The purpose of the present invention is to provide a guaiacyl vinyl ketone production method that has higher reaction efficiency and is better suited to industrial-scale production than conventional techniques. Said purpose is achieved by a method that produces high-purity guaiacyl vinyl ketone, the method being efficient under moderate conditions and including a step for obtaining guaiacyl vinyl ketone by bringing a basic substance and a 3-halogen-1-(4-hydroxy-3-methoxyphenyl)-1-propanone that is represented by general formula (1) into contact in a solvent.

Description

グアイアシルビニルケトンの製造方法Method for producing guaiacyl vinyl ketone 関連出願の相互参照Cross-reference of related applications
本出願は、２０１４年３月５日出願の日本特願２０１４－４３０６６号の優先権を主張し、その全記載はここに開示として援用される。 This application claims the priority of Japanese Patent Application No. 2014-43066 filed on Mar. 5, 2014, the entire description of which is incorporated herein by reference.
本発明は、グアイアシルビニルケトン（１－(４－ヒドロキシ－３－メトキシフェニル)－２－プロペン－１－オン）を製造する方法に関する。 The present invention relates to a process for producing guaiacyl vinyl ketone (1- (4-hydroxy-3-methoxyphenyl) -2-propen-1-one).
グアイアシルビニルケトン（１－(４－ヒドロキシ－３－メトキシフェニル)－２－プロペン－１－オン）は重合性のビニル基を有することから、高分子の合成の際にモノマー成分として用いられる有用な物質である。また分子内にカルボニル基を含むことから、光感受性などの特性も期待ができる化合物である。 Guayacyl vinyl ketone (1- (4-hydroxy-3-methoxyphenyl) -2-propen-1-one) has a polymerizable vinyl group and is useful as a monomer component in the synthesis of polymers. It is a serious substance. Further, since it contains a carbonyl group in the molecule, it is a compound that can be expected to have characteristics such as photosensitivity.
グアイアシルビニルケトンの製造方法としては、３－ヒドロキシ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンを、ジメチルフォルムアミド中で長時間煮沸する方法が知られている（下記非特許文献１を参照、該文献の記載はここに開示として援用される）。 As a method for producing guaiacyl vinyl ketone, a method is known in which 3-hydroxy-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is boiled in dimethylformamide for a long time (non-discussed below). See Patent Document 1, the description of which is incorporated herein by reference).
グアイアシルビニルケトンとは構造が相違する４－ヒドロキシフェニルビニルケトンの製造方法として、３－クロロ－１－(４－メトキシフェニル)－１－プロパノンを出発物質とし、塩化アルミニウムのようなルイス酸を用いた脱塩酸反応を経由することにより、４－ヒドロキシフェニルビニルケトンが得られることが下記特許文献１（該文献の記載はここに開示として援用される）に記載されている。また、特許文献１には、ルイス酸に代えて、塩基性物質を用いる場合、反応が円滑に進行しないことが記載されている。 As a method for producing 4-hydroxyphenyl vinyl ketone having a structure different from that of guaiacyl vinyl ketone, a Lewis acid such as aluminum chloride is used starting from 3-chloro-1- (4-methoxyphenyl) -1-propanone. It is described in the following Patent Document 1 (the description of this document is incorporated herein by reference) that 4-hydroxyphenyl vinyl ketone can be obtained via the dehydrochlorination reaction used. Patent Document 1 describes that when a basic substance is used instead of Lewis acid, the reaction does not proceed smoothly.
一方、グアイアシルビニルケトンとは構造が相違する１－（４－ヒドロキシフェニル）－２－メチル－２－プロペン－１－オンの製造方法として、３－クロロ－１－（４－ヒドロキシフェニル）－２－メチル－プロパン－１－オンを出発物質とし、ナトリウムエトキシドを作用させることにより、１－（４－ヒドロキシフェニル）－２－メチル－２－プロペン－１－オンが得られることが下記非特許文献２（該文献の記載はここに開示として援用される）に記載されている。 On the other hand, as a method for producing 1- (4-hydroxyphenyl) -2-methyl-2-propen-1-one having a structure different from that of guaiacyl vinyl ketone, 3-chloro-1- (4-hydroxyphenyl)- It is shown that 1- (4-hydroxyphenyl) -2-methyl-2-propen-1-one can be obtained by reacting sodium ethoxide with 2-methyl-propan-1-one as a starting material. It is described in Patent Document 2 (the description of the document is incorporated herein by reference).
特開２００４－１８９７１５号公報JP 2004-189715 A
非特許文献１に記載の方法によれば、グアイアシルビニルケトンが得られる。しかし、該方法は、高温下で反応しなければならず、さらに反応後に回収の難しい高沸点の溶媒を用いる点で、工業的規模でのグアイアシルビニルケトンの製造方法として不適なものである。また収率も２４％と低く、反応効率が非常に低いという問題がある。 According to the method described in Non-Patent Document 1, guaiacyl vinyl ketone is obtained. However, this method is unsuitable as a method for producing guaiacyl vinyl ketone on an industrial scale in that a high-boiling solvent that must be reacted at a high temperature and difficult to recover after the reaction is used. Further, there is a problem that the yield is as low as 24% and the reaction efficiency is very low.
そこで、グアイアシルビニルケトンと同じフェニルビニルケトン系化合物を製造する方法である、特許文献１及び非特許文献２に記載の方法を参照して、グアイアシルビニルケトンを製造しようとすることが考えられる。特許文献１及び非特許文献２に記載の方法は、出発物質として３－クロロ－１－(４－メトキシフェニル)－１－プロパノン又は３－クロロ－１－（４－ヒドロキシフェニル）－２－メチル－プロパン－１－オンを用いて、４－ヒドロキシフェニルビニルケトン又はその誘導体を製造する方法である。しかし、これらの方法は、反応条件が正反対であり、しかも一方の文献には、他方の文献に記載の反応条件では反応が円滑に進行しないことが記載されている。 Therefore, it is conceivable to produce guaiacyl vinyl ketone with reference to the methods described in Patent Document 1 and Non-Patent Document 2, which are methods for producing the same phenyl vinyl ketone compound as guaiacyl vinyl ketone. . The methods described in Patent Document 1 and Non-Patent Document 2 use 3-chloro-1- (4-methoxyphenyl) -1-propanone or 3-chloro-1- (4-hydroxyphenyl) -2-methyl as a starting material. A method for producing 4-hydroxyphenyl vinyl ketone or a derivative thereof using propan-1-one. However, these methods have opposite reaction conditions, and one document describes that the reaction does not proceed smoothly under the reaction conditions described in the other document.
このように、見かけ上、一部において化学構造が類似していると思われる出発物質であっても、反応条件が違えば、目的とする生成物が得られない可能性があることから、反応系を類推することは困難である。特に、非特許文献２に記載の塩基性物質を用いる反応条件は、カルボニル基のα水素が脱離してアルドール反応に進む条件やマイケル付加反応条件と重複すること、生成したビニルケトン類が反応して付加反応や重合反応が生じる可能性があることなどから、塩基性物質を用いる反応条件によって所望の目的物が得られるであろうと予測することは非常に困難である。 In this way, even starting materials that seem to have similar chemical structures in part, the target product may not be obtained if the reaction conditions are different. It is difficult to analogize the system. In particular, the reaction conditions using the basic substance described in Non-Patent Document 2 overlap with the conditions in which α-hydrogen of the carbonyl group is eliminated to proceed to the aldol reaction and Michael addition reaction conditions, and the generated vinyl ketones react. Since there is a possibility that an addition reaction or a polymerization reaction may occur, it is very difficult to predict that a desired object will be obtained depending on reaction conditions using a basic substance.
そこで、本発明は、非特許文献１に記載の方法に比して、反応効率が高く、かつ、工業的規模での生産に適したグアイアシルビニルケトンを製造する方法を提供することを、発明が解決しようとする課題とした。 Therefore, the present invention provides a method for producing guaiacyl vinyl ketone having a high reaction efficiency and suitable for production on an industrial scale as compared with the method described in Non-Patent Document 1. Was the problem to be solved.
本発明者らは、グアイアシルビニルケトンを製造するにあたり、出発物質及び反応条件について鋭意研究を積み重ねたところ、出発物質として３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンと塩基性物質とを反応させることによりグアイアシルビニルケトンを得ることに成功した。しかも、驚くべきことに、反応条件は極めて温和な条件に設定することができ、例えばアルコール類や水を溶媒とした場合には、室温付近で反応させることができることを見出した。また、使用する塩基性物質として苛性ソーダをはじめとする汎用の塩基性化合物が使用でき、さらに反応効率が高いことを見出した。本発明はこのような成功例や知見に基づき完成された発明である。 In the production of guaiacyl vinyl ketone, the present inventors have made extensive studies on starting materials and reaction conditions. As a starting material, 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1- We succeeded in obtaining guaiacyl vinyl ketone by reacting propanone with basic substances. Moreover, surprisingly, it has been found that the reaction conditions can be set to extremely mild conditions. For example, when alcohols or water is used as a solvent, the reaction can be performed at around room temperature. Further, it has been found that general basic compounds such as caustic soda can be used as the basic substance to be used, and the reaction efficiency is high. The present invention has been completed based on such successful examples and knowledge.
したがって本発明によれば、溶媒中で、下記一般式（１）
Figure JPOXMLDOC01-appb-C000002
 　　　　（１）
（式中、Ｘはハロゲン原子を示す。）
で表わされる３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンと塩基性物質とを接触させることにより、グアイアシルビニルケトンを得る工程を含む、グアイアシルビニルケトンの製造方法が提供される。 Therefore, according to the present invention, in the solvent, the following general formula (1)
Figure JPOXMLDOC01-appb-C000002
 (1)
(In the formula, X represents a halogen atom.)
The production of guaiacyl vinyl ketone, comprising the step of obtaining guaiacyl vinyl ketone by contacting 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone represented by the formula: A method is provided.
好ましくは、本発明の製造方法において、前記ハロゲン原子が塩素原子又は臭素原子である。 Preferably, in the production method of the present invention, the halogen atom is a chlorine atom or a bromine atom.
好ましくは、本発明の製造方法において、前記溶媒がアルコール類又は水である。 Preferably, in the production method of the present invention, the solvent is an alcohol or water.
好ましくは、本発明の製造方法において、前記塩基性物質が、アルカリ金属の水酸化物、アルカリ金属の炭酸塩、アルカリ金属の重炭酸塩及びアルカリ金属のアルコキシドからなる群から選ばれる塩基性物質である。 Preferably, in the production method of the present invention, the basic substance is a basic substance selected from the group consisting of alkali metal hydroxides, alkali metal carbonates, alkali metal bicarbonates, and alkali metal alkoxides. is there.
好ましくは、本発明の製造方法において、前記溶媒が水であり、かつ、前記塩基性物質がアルカリ金属の水酸化物、アルカリ金属の炭酸塩及びアルカリ金属の重炭酸塩からなる群から選ばれる塩基性物質である。 Preferably, in the production method of the present invention, the solvent is water, and the basic substance is selected from the group consisting of alkali metal hydroxides, alkali metal carbonates, and alkali metal bicarbonates. It is a sex substance.
本発明の製造方法によれば、非特許文献１に記載の方法に比して、３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンから、温和な条件で、回収の容易な溶媒や汎用の塩基性物質を使用して収率よくグアイアシルビニルケトンを製造することができる。したがって、本発明の製造方法によれば、工業的規模でのグアイアシルビニルケトンの製造が可能である。 According to the production method of the present invention, recovery from 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone under mild conditions compared to the method described in Non-Patent Document 1. Thus, guaiacyl vinyl ketone can be produced with good yield using a simple solvent or a general-purpose basic substance. Therefore, according to the production method of the present invention, it is possible to produce guaiacyl vinyl ketone on an industrial scale.
図１は、参考例１で得られた高分子膜状物の写真図である。1 is a photograph of the polymer film obtained in Reference Example 1. FIG.
以下、本発明の詳細について説明する。
本発明のグアイアシルビニルケトンの製造方法は、溶媒中で、下記一般式（１）
Figure JPOXMLDOC01-appb-C000003
 　　　（１）
（式中、Ｘはハロゲン原子を示す。）
で表わされる３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンと塩基性物質とを接触させることにより、グアイアシルビニルケトンを得る工程を少なくとも含む。 Details of the present invention will be described below.
The method for producing the guaiacyl vinyl ketone of the present invention comprises the following general formula (1) in a solvent.
Figure JPOXMLDOC01-appb-C000003
 (1)
(In the formula, X represents a halogen atom.)
At least a step of obtaining a guaiacyl vinyl ketone by contacting 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone represented by formula (I) with a basic substance.
３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンは、上記一般式（１）に示されているとおり、プロパノン骨格の３位の炭素原子にハロゲン原子が付加された化合物である。３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンは、上記一般式（１）に示される構造式を有するものであれば特に限定されず、例えば、分子中のハロゲン原子はフッ素原子、塩素原子、臭素原子、ヨウ素原子などであることができ、好ましくは塩素原子及び臭素原子である。 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone has a halogen atom added to the 3-position carbon atom of the propanone skeleton as shown in the general formula (1) above. A compound. The 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is not particularly limited as long as it has the structural formula represented by the general formula (1). The atoms can be fluorine atoms, chlorine atoms, bromine atoms, iodine atoms and the like, preferably chlorine atoms and bromine atoms.
３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンの取得方法は特に限定されないが、例えば、３－ヒドロキシ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンから製造することができる。具体的には、非特許文献２に記載されている、３－ヒドロキシ－１－（４－ヒドロキシフェニル）－２－メチル－プロパン－１－オンを濃塩酸中で加熱して３－クロロ－１－（４－ヒドロキシフェニル）－２－メチル－プロパン－１－オンを合成する方法を応用すれば、３－ヒドロキシ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンから、良好な収率及び純度で、３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンが得られる。 The method for obtaining 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is not particularly limited. For example, 3-hydroxy-1- (4-hydroxy-3-methoxyphenyl) -1- Can be manufactured from propanone. Specifically, 3-hydroxy-1- (4-hydroxyphenyl) -2-methyl-propan-1-one described in Non-Patent Document 2 is heated in concentrated hydrochloric acid to give 3-chloro-1 By applying the method of synthesizing-(4-hydroxyphenyl) -2-methyl-propan-1-one, it is possible to obtain a good result from 3-hydroxy-1- (4-hydroxy-3-methoxyphenyl) -1-propanone. In yield and purity, 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is obtained.
より具体的には、３－ヒドロキシ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンを、約２０質量倍の３０～５０質量％のハロゲン化水素酸水溶液中で、４０～９０℃で、０．５～２時間程度反応させることにより、３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンを、ほぼ定量的な収率で、結晶としてろ過分離することができる。この際に使用されるハロゲン化水素酸は特に限定されないが、例えば、塩酸、臭化水素酸、フッ化水素酸、ヨウ化水素酸などが挙げられ、好ましくは塩酸及び臭化水素酸である。 More specifically, 3-hydroxy-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is used in an aqueous solution of hydrohalic acid of 30 to 50% by mass, about 20 times by mass, in an amount of 40 to 90%. By reacting at 0.5 ° C. for about 0.5 to 2 hours, 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is separated by filtration as crystals in an almost quantitative yield. be able to. The hydrohalic acid used at this time is not particularly limited, and examples thereof include hydrochloric acid, hydrobromic acid, hydrofluoric acid, hydroiodic acid, and the like, preferably hydrochloric acid and hydrobromic acid.
３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンの好ましい態様としては、操作性及び安全性の観点から、３－クロロ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノン及び３－ブロモ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンが挙げられるが、より好ましくは３－クロロ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンである。 A preferred embodiment of 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is 3-chloro-1- (4-hydroxy-3-methoxyphenyl) from the viewpoint of operability and safety. ) -1-propanone and 3-bromo-1- (4-hydroxy-3-methoxyphenyl) -1-propanone, more preferably 3-chloro-1- (4-hydroxy-3-methoxyphenyl) -1-propanone.
３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンの使用量は系内の混合が可能な量であれば特に限定されず、例えば、溶媒の容量に対して０．１％（Ｗ／Ｖ）から５０％（Ｗ／Ｖ）とすることができ、好ましくは１％（Ｗ／Ｖ）～１０％（Ｗ／Ｖ）である。 The amount of 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is not particularly limited as long as it can be mixed in the system. It can be 1% (W / V) to 50% (W / V), preferably 1% (W / V) to 10% (W / V).
本発明の製造方法に用いる溶媒としては３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンに対して可溶性があるものであれば特に限定されないが、例えば、水、メタノール、エタノール、イソプロパノール、ブタノールなどのアルコール類；ジエチルエーテル、テトラヒドロフラン、ジオキサン、グライムなどのエーテル類；ベンゼン、トルエン、キシレン、ヘキサン、シクロヘキサンなどの炭化水素類；クロロフォルム、ジクロロメタン、クロロベンゼンなどのハロゲン化炭化水素類；アセトン、メチルエチルケトン、メチルイソブチルケトンなどのケトン類；ジメチルフォルムアミド、ジメチルイミダゾリジノン、ジメチルスルホキシドなどの非プロトン性極性溶媒；酢酸エチル、酢酸ブチルなどのエステル類などが挙げられるが、安全性、操作性及び塩基性物質の溶解性を考慮すれば、水及びアルコール類が好ましい。これらの溶媒は、単独又は２種以上を混合した混合溶媒であってもよい。 The solvent used in the production method of the present invention is not particularly limited as long as it is soluble in 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone. For example, water, methanol Alcohols such as ethanol, isopropanol and butanol; ethers such as diethyl ether, tetrahydrofuran, dioxane and glyme; hydrocarbons such as benzene, toluene, xylene, hexane and cyclohexane; halogenated hydrocarbons such as chloroform, dichloromethane and chlorobenzene Ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone; aprotic polar solvents such as dimethylformamide, dimethylimidazolidinone, and dimethyl sulfoxide; esters such as ethyl acetate and butyl acetate Although s and the like, safety, considering the solubility of the operability and the basic substance, water and alcohols are preferred. These solvents may be a single solvent or a mixed solvent in which two or more kinds are mixed.
溶媒の使用量は、３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンの使用量によって適宜変更することができ、特に限定されないが、例えば、３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンが流動する量として、３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンに対して1～１００質量倍であり、３～５０質量倍が好ましい。 The amount of the solvent used can be appropriately changed according to the amount of 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone, and is not particularly limited. For example, 3-halogeno-1- The amount of (4-hydroxy-3-methoxyphenyl) -1-propanone flowing is 1 to 100 times the mass of 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone. 3 to 50 times by mass is preferable.
使用する塩基性物質は、溶媒が塩基性（アルカリ）になることに寄与する物質であれば特に限定されないが、例えば、苛性ソーダ（ＮａＯＨ）、苛性カリ（ＫＯＨ）、水酸化カルシウム、水酸化マグネシウム、炭酸ソーダ（Ｎａ２ＣＯ３）、炭酸カリ（Ｋ２ＣＯ３）、重炭酸ソーダ（ＮａＨＣＯ３）、重炭酸カリ（ＫＨＣＯ３）などの無機性塩基性物質；ナトリウムメトキシド、ナトリウムエトキシド、カリウムメトキシド、カリウムエトキシド、アンモニア、炭酸アンモニウム、重炭酸アンモニウム、ピリジン、トリエチルアミン、酢酸ソーダなどの有機性塩基性物質などが挙げられるが、この中でも、アルカリ金属の水酸化物、アルカリ金属の炭酸塩、アルカリ金属の重炭酸塩及びアルカリ金属のアルコキシドは、廃棄処理が簡単であることなどの理由から、好適に使用できる。これらの塩基性物質は、単独又は２種以上を混合したものであってもよい。 The basic substance to be used is not particularly limited as long as the solvent contributes to becoming basic (alkaline). For example, caustic soda (NaOH), caustic potash (KOH), calcium hydroxide, magnesium hydroxide, carbonate Inorganic basic substances such as soda (Na 2 CO 3 ), potassium carbonate (K 2 CO 3 ), sodium bicarbonate (NaHCO 3 ), potassium bicarbonate (KHCO 3 ); sodium methoxide, sodium ethoxide, potassium methoxide, Organic basic substances such as potassium ethoxide, ammonia, ammonium carbonate, ammonium bicarbonate, pyridine, triethylamine, sodium acetate, etc. are mentioned. Among them, alkali metal hydroxides, alkali metal carbonates, alkali metals The bicarbonates and alkali metal alkoxides are easy to dispose of. For reasons such as that it can be suitably used. These basic substances may be used alone or in combination of two or more.
特に、溶媒として水を用い、かつ、塩基性物質としてアルカリ金属の水酸化物、アルカリ金属の炭酸塩及び／又はアルカリ金属の重炭酸塩を用いる場合は、本発明の製造方法は、経済性が高く、さらに溶液が強塩基性となり均一系で反応することができることから、簡便で、廃液の問題が軽減された方法となるという利点を有する。 In particular, when water is used as the solvent and an alkali metal hydroxide, alkali metal carbonate and / or alkali metal bicarbonate is used as the basic substance, the production method of the present invention is economical. Further, since the solution becomes strongly basic and can react in a homogeneous system, it has an advantage that it is simple and the method of reducing the waste solution is reduced.
塩基性物質の使用量は、塩基性物質の種類、３－ハロゲノ－１－（４－ヒドロキシ－３－メトキシフェニル）－１－プロパノンや溶媒の使用量などによって適宜変更でき特に限定されないが、例えば、３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンから脱離するハロゲン化水素酸を中和できる量であり、好ましくは該ハロゲン化水素酸の０．８５等量～５．０等量であり、より好ましくは１．０～３．０等量である。 The amount of the basic substance used can be appropriately changed depending on the kind of the basic substance, the amount of 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone or the solvent used, and is not particularly limited. , 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone in an amount capable of neutralizing hydrohalic acid, preferably 0.85 equivalent of the hydrohalic acid -5.0 equivalents, more preferably 1.0-3.0 equivalents.
３－ハロゲノ－１－（４－ヒドロキシ－３－メトキシフェニル）－１－プロパノンと塩基性物質との接触手段は、溶媒中で３－ハロゲノ－１－（４－ヒドロキシ－３－メトキシフェニル）－１－プロパノンと塩基性物質とが接触すれば特に限定されず、例えば、所定量の溶媒を加えた容器に、３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンの適当量を加えて撹拌しながら３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンを溶媒中に溶解又は拡散させ、次いで塩基性物質を徐々に添加していくことが好ましい。３－ハロゲノ－１－（４－ヒドロキシ－３－メトキシフェニル）－１－プロパノンと塩基性物質とが接触して反応することにより、グアイアシルビニルケトンが生成される。反応時の温度や時間などの条件は特に限定されず、例えば、０℃～１００℃であり、好ましくは１５℃～８０℃であり、より好ましくは室温付近である。具体的には、アルコール類を溶媒とした場合には、１０℃～４０℃とすることが好ましい。反応の時間は、溶媒や塩基性物質の性質、反応温度などによって適宜設定することができるが、例えば、０．５～５．０時間程度であり、好ましくは１．０～３．０時間程度である。反応の終点は、実施例１に記載の条件のＨＰＬＣや薄層クロマトグラフなどの３－ハロゲノ－１－（４－ヒドロキシ－３－メトキシフェニル）－１－プロパノンやグアイアシルビニルケトンを検出する方法で、原料化合物の消失や生成物の生成量を確認するなどして決定することができる。 The means for contacting 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone with a basic substance is obtained by using 3-halogeno-1- (4-hydroxy-3-methoxyphenyl)-in a solvent. There is no particular limitation as long as 1-propanone comes into contact with a basic substance. For example, 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is added to a container to which a predetermined amount of solvent is added. While adding an appropriate amount and stirring, 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is dissolved or diffused in a solvent, and then a basic substance is gradually added. preferable. When 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone and a basic substance are brought into contact with each other and reacted, guaiacyl vinyl ketone is produced. Conditions such as temperature and time during the reaction are not particularly limited, and are, for example, 0 ° C. to 100 ° C., preferably 15 ° C. to 80 ° C., and more preferably around room temperature. Specifically, when alcohol is used as a solvent, the temperature is preferably 10 ° C to 40 ° C. The reaction time can be appropriately set depending on the nature of the solvent and basic substance, the reaction temperature, and the like. For example, it is about 0.5 to 5.0 hours, preferably about 1.0 to 3.0 hours. It is. The end point of the reaction is a method for detecting 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone or guaiacyl vinyl ketone, such as HPLC or thin layer chromatograph under the conditions described in Example 1. Thus, it can be determined by confirming the disappearance of the raw material compound and the production amount of the product.
また、本発明の製造方法では、３－ヒドロキシ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンとハロゲン化水素酸水溶液とを反応させることにより得られた３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンを、ハロゲン化水素酸水溶液と非相溶性の有機溶媒で抽出して、次いでこの有機溶媒に塩基性物質を加えることにより、３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンと塩基性物質とを接触させることにより達成できる。 Further, in the production method of the present invention, 3-halogen-1-one obtained by reacting 3-hydroxy-1- (4-hydroxy-3-methoxyphenyl) -1-propanone with an aqueous hydrohalic acid solution. By extracting (4-hydroxy-3-methoxyphenyl) -1-propanone with an organic solvent incompatible with an aqueous hydrohalic acid solution and then adding a basic substance to the organic solvent, 3-halogeno- This can be achieved by bringing 1- (4-hydroxy-3-methoxyphenyl) -1-propanone into contact with a basic substance.
ハロゲン化水素酸水溶液と非相溶性の有機溶媒としては、３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンが溶解し得る有機溶媒であれば特に限定されないが、例えば、ベンゼン、トルエン、キシレン、ヘキサン、シクロヘキサンなどの炭化水素類；クロロフォルム、ジクロロメタン、クロロベンゼンなどのハロゲン化炭化水素類；酢酸エチル、酢酸ブチルなどのエステル類；メチルエチルケトン、メチルイソブチルケトンなどのケトン類；前記した本発明の製造方法に用いる溶媒などを挙げることができ、これらを単独又は２種以上を混合したものであってもよい。 The organic solvent incompatible with the hydrohalic acid aqueous solution is not particularly limited as long as it is an organic solvent in which 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone can be dissolved. Hydrocarbons such as benzene, toluene, xylene, hexane and cyclohexane; halogenated hydrocarbons such as chloroform, dichloromethane and chlorobenzene; esters such as ethyl acetate and butyl acetate; ketones such as methyl ethyl ketone and methyl isobutyl ketone; The solvent etc. which are used for the manufacturing method of this invention which were made can be mentioned, These may be used individually or in mixture of 2 or more types.
本発明の製造方法では、溶媒中で、３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンと塩基性物質とを接触させることにより、グアイアシルビニルケトンが得られる。グアイアシルビニルケトンは、下記式（２）に示す１－(４－ヒドロキシ－３－メトキシフェニル)－２－プロペン－１－オンであり、重合性官能基であるビニル基を有することから、高分子材料のモノマー成分として使用可能な有用物質である。
Figure JPOXMLDOC01-appb-C000004
 　（２） In the production method of the present invention, guaiacyl vinyl ketone is obtained by contacting 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone with a basic substance in a solvent. Guayacyl vinyl ketone is 1- (4-hydroxy-3-methoxyphenyl) -2-propen-1-one represented by the following formula (2), and has a vinyl group that is a polymerizable functional group. It is a useful substance that can be used as a monomer component of molecular materials.
Figure JPOXMLDOC01-appb-C000004
 (2)
グアイアシルビニルケトンは、中性付近では水に対して不溶性のオイル状を呈する。そこで、反応終了後は、水と水に対して非相溶性の有機溶媒との二相系として、グアイアシルビニルケトンを有機溶媒層に移行させ、かつ、反応の結果生成した塩類を水層に移行させることにより、目的物質であるグアイアシルビニルケトンと水に可溶性の物質とを分離することが好ましい。 Guaacyl vinyl ketone is in the form of an oil that is insoluble in water near neutrality. Therefore, after completion of the reaction, as a two-phase system of water and an organic solvent incompatible with water, guaiacyl vinyl ketone is transferred to the organic solvent layer, and salts generated as a result of the reaction are transferred to the aqueous layer. It is preferable to separate the target substance, guaiacyl vinyl ketone, and the substance soluble in water by transferring the substance.
例えば、反応終了後に、反応混合物に水及び酸を加え、又は水を加えた後に酸を加えて、過剰の塩基性物質を中和する。得られた中和物に、必要に応じて反応に使用した溶媒を留去して、水に非相溶性の有機溶媒を加えて、水層と有機溶媒層との二相系として、グアイアシルビニルケトンを有機溶媒層に移行させ抽出する。 For example, after completion of the reaction, water and acid are added to the reaction mixture, or water is added and then acid is added to neutralize excess basic material. If necessary, the solvent used in the reaction is distilled off to the neutralized product, and an incompatible organic solvent is added to water to form a two-phase system consisting of an aqueous layer and an organic solvent layer. Vinyl ketone is transferred to the organic solvent layer and extracted.
中和に用いる酸は反応混合物中の塩基性物質を中和し得る酸であれば特に限定されず、例えば、塩酸、硫酸、臭化水素酸、リン酸、酢酸などが使用できる。中和後の水層の液性は、ｐＨとして、３．０～９．０とするのが好ましい。また、この際に用いる抽出用の水に非相溶性の有機溶媒としては、グアイアシルビニルケトンが溶解し得るものであれば特に限定されないが、例えば、ベンゼン、トルエン、キシレン、ヘキサン、シクロヘキサンなどの炭化水素類；クロロフォルム、ジクロロメタン、クロロベンゼンなどのハロゲン化炭化水素類；酢酸エチル、酢酸ブチルなどのエステル類；メチルエチルケトン、メチルイソブチルケトンなどのケトン類；ブタノール、ヘキサノールなどのアルコール類などが挙げられ、これらを単独で、又は２種以上を混合して使用できる。 The acid used for neutralization is not particularly limited as long as it can neutralize the basic substance in the reaction mixture. For example, hydrochloric acid, sulfuric acid, hydrobromic acid, phosphoric acid, acetic acid and the like can be used. The liquidity of the aqueous layer after neutralization is preferably set to 3.0 to 9.0 as pH. Further, the organic solvent incompatible with the extraction water used in this case is not particularly limited as long as guaiacyl vinyl ketone can be dissolved, but for example, benzene, toluene, xylene, hexane, cyclohexane, etc. Hydrocarbons; halogenated hydrocarbons such as chloroform, dichloromethane and chlorobenzene; esters such as ethyl acetate and butyl acetate; ketones such as methyl ethyl ketone and methyl isobutyl ketone; and alcohols such as butanol and hexanol. Can be used alone or in admixture of two or more.
グアイアシルビニルケトンを含む有機溶媒層からグアイアシルビニルケトンを得る方法は特に限定されず、例えば、該有機溶媒層から常圧下又は減圧下に有機溶媒を留去することにより、グアイアシルビニルケトンを無色～わずかに褐色に着色した液体として得ることができる。 The method for obtaining guaiacyl vinyl ketone from the organic solvent layer containing guaiacyl vinyl ketone is not particularly limited. For example, by removing the organic solvent from the organic solvent layer under normal pressure or reduced pressure, guaiacyl vinyl ketone is obtained. It can be obtained as a colorless to slightly brown liquid.
反応後の溶液からグアイアシルビニルケトンを抽出する操作における、水、酸及び水に対して非相溶性である有機溶媒の量は特に限定されず、当業者により適宜設定できる。また、グアイアシルビニルケトンの収率を高めるために、抽出の際に分離された水層に水に対して非相溶性である有機溶媒を添加して再抽出する操作を１～複数回繰返してもよい。さらに、高純度のグアイアシルビニルケトンを得るために、抽出後の有機溶媒層を水などで１～複数回洗浄してもよい。 In the operation of extracting guaiacyl vinyl ketone from the solution after the reaction, the amount of water, acid, and the organic solvent that is incompatible with water is not particularly limited and can be appropriately set by those skilled in the art. Further, in order to increase the yield of guaiacyl vinyl ketone, the operation of adding an organic solvent incompatible with water to the aqueous layer separated during extraction and repeating the extraction one or more times is repeated. Also good. Furthermore, in order to obtain high-purity guaiacyl vinyl ketone, the organic solvent layer after extraction may be washed one or more times with water or the like.
上記した操作を通じて、グアイアシルビニルケトンは、各成分の含有量、塩基性物質及び溶媒の組合せ、溶液のｐＨ、反応温度や時間などの条件を適宜設定することにより、９０％以上、好ましくは９５％以上の高純度で得ることが可能である。したがって、本発明の製造方法によって得られたグアイアシルビニルケトンは、その後の精製操作を経ることなく、その状態のままで高分子化合物の製造のためのモノマー成分として利用できる。 Through the above-described operation, the guaiacyl vinyl ketone is 90% or more, preferably 95%, by appropriately setting the conditions such as the content of each component, the combination of basic substance and solvent, pH of the solution, reaction temperature and time. % Or higher purity can be obtained. Therefore, the guaiacyl vinyl ketone obtained by the production method of the present invention can be used as a monomer component for producing a polymer compound as it is without undergoing a subsequent purification operation.
さらに精製してより高純度なグアイアシルビニルケトンを得るためには、後述する実施例１に記載されているような、本発明の製造方法によって得られたグアイアシルビニルケトンを、シリカゲルや逆相Ｃ－１８充填剤などを用いたカラム処理や真空蒸留などの通常知られている有機化合物を精製する手段に供すればよい。 In order to further purify and obtain a higher-purity guaiacyl vinyl ketone, the guaiacyl vinyl ketone obtained by the production method of the present invention as described in Example 1, which will be described later, is added to silica gel or reverse phase. What is necessary is just to use for the means which refine | purifies normally known organic compounds, such as column processing using a C-18 filler, and vacuum distillation.
本発明の製造方法では、本発明の目的を達成し得る限り、上記した工程の前段若しくは後段又は工程中に、種々の工程や操作を加入することができる。 In the production method of the present invention, as long as the object of the present invention can be achieved, various processes and operations can be added before or after the above-described process.
本発明の製造方法の具体的態様は、例えば、以下のとおりであるが、本発明はこれに限定されるものではない。
［具体的態様１］
水、アルコール類又はこれらの混合溶媒に、３－ハロゲノ－１－（４－ヒドロキシ－３－メトキシフェニル）－１－プロパノンを加えて、１０～４５℃で撹拌することにより、３－ハロゲノ－１－（４－ヒドロキシ－３－メトキシフェニル）－１－プロパノン含有溶液を得る。得られた３－ハロゲノ－１－（４－ヒドロキシ－３－メトキシフェニル）－１－プロパノン含有溶液を撹拌しながら、無機又は有機の塩基性物質を少量ずつ１０～４５℃下で加える。得られた塩基性物質を添加した溶液を数分間～数時間、１０～８０℃で撹拌して反応させる。３－ハロゲノ－１－（４－ヒドロキシ－３－メトキシフェニル）－１－プロパノンの消失を確認した後、反応後の溶液に、水及び酸を徐々に滴下してｐＨを３．０～９．０に調整し、次いで必要に応じてアルコール類を留去した後に、水に対して非相溶性である有機溶媒を加えてグアイアシルビニルケトンを抽出分離する。また、該有機溶媒を使用して水層を再抽出する。これを１～複数回繰返す。得られた抽出液（有機溶媒層）を合わせ、水で洗浄する。洗浄後の抽出液から、該有機溶媒を減圧下又は低温下に留去し、グアイアシルビニルケトンを得る。 Although the specific aspect of the manufacturing method of this invention is as follows, for example, this invention is not limited to this.
[Specific Embodiment 1]
3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone is added to water, alcohols or a mixed solvent thereof, and stirred at 10 to 45 ° C. to give 3-halogeno-1 A solution containing-(4-hydroxy-3-methoxyphenyl) -1-propanone is obtained. While stirring the resulting 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone-containing solution, an inorganic or organic basic substance is added in small portions at 10 to 45 ° C. The resulting solution with the basic substance added is reacted by stirring at 10-80 ° C. for several minutes to several hours. After confirming disappearance of 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone, water and an acid were gradually added dropwise to the solution after the reaction to adjust the pH to 3.0 to 9. After adjusting to 0 and then distilling off alcohols as necessary, an organic solvent incompatible with water is added to extract and separate guaiacyl vinyl ketone. The aqueous layer is re-extracted using the organic solvent. Repeat this one or more times. The obtained extracts (organic solvent layer) are combined and washed with water. From the washed extract, the organic solvent is distilled off under reduced pressure or low temperature to obtain guaiacyl vinyl ketone.
本発明の製造方法によって得られるグアイアシルビニルケトンは、重合性官能基であるビニル基を有することから、高分子物質を製造する際のモノマー成分とすることができ、例えば、図１に示すように、それ単体で、又は架橋剤や他のモノマー成分と供に重合させることができる。さらに、グアイアシルビニルケトンは、レジストなどの光感受性組成物の製造用原料として有用である。 Since the guaiacyl vinyl ketone obtained by the production method of the present invention has a vinyl group which is a polymerizable functional group, it can be used as a monomer component when producing a polymer substance. For example, as shown in FIG. In addition, it can be polymerized alone or together with a crosslinking agent or other monomer component. Furthermore, guaiacyl vinyl ketone is useful as a raw material for producing a photosensitive composition such as a resist.
以下、本発明を実施例によりさらに詳細に説明するが、本発明はこれら実施例に限定されるものではなく、本発明の課題を解決し得る限り、本発明は種々の態様をとることができる。 Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples, and the present invention can take various modes as long as the problems of the present invention can be solved. .
［実施例１］
２０ｍｌのエタノールを加えた１００ｍｌの三角フラスコに、３－クロロ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノン　１．４１ｇ（０．００６６モル）を室温で撹拌しながら溶解させた。この溶液に、ナトリウムエトキシド　０．９ｇ（０．０１３２モル）を室温下に加え、１．５時間反応させて、グアイアシルビニルケトンを得た。以下のＨＰＬＣ条件では、原料の３－クロロ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンは保持時間９．９分で検出され、目的物のグアイアシルビニルケトンは保持時間８．９分で検出された。反応終了後には、原料のピークである９．９分の保持時間のピークは消失した。 [Example 1]
In a 100 ml Erlenmeyer flask to which 20 ml of ethanol was added, 1.41 g (0.0066 mol) of 3-chloro-1- (4-hydroxy-3-methoxyphenyl) -1-propanone was dissolved at room temperature with stirring. . To this solution, 0.9 g (0.0132 mol) of sodium ethoxide was added at room temperature and reacted for 1.5 hours to obtain guaiacyl vinyl ketone. Under the following HPLC conditions, the raw material 3-chloro-1- (4-hydroxy-3-methoxyphenyl) -1-propanone was detected with a retention time of 9.9 minutes, and the target guaiacyl vinyl ketone was detected with a retention time of 8 minutes. Detected at 9 minutes. After completion of the reaction, the peak of the retention time of 9.9 minutes, which is the peak of the raw material, disappeared.
ＨＰＬＣ条件：
装置：ウォーターズ２７９５、２９９８
カラム：Ｘ－ｂｒｉｄｇｅＣ１８，３．５μ，径４．６ｍｍ×１００ｍｍ，（３０℃）
キャリヤー：（Ａ）２ｍＭ－ＮＨ４ＯＡｃ　ａｑ．（０．０５％Ｖ／Ｖ　Ｆｏｒｍｉｃ　ａｃｉｄ）、（Ｂ）ＭｅＯＨ
グラジエント：５％Ｖ／Ｖ　ＭｅＯＨ（１ｍｉｎ），ＭｅＯＨ　５％Ｖ／Ｖ→９５％Ｖ／Ｖ（１～１５ｍｉｎ），９５％Ｖ／Ｖ　ＭｅＯＨ（１５～１８ｍｉｎ）
検出器：ＵＶ３００ｎｍ HPLC conditions:
Apparatus: Waters 2795, 2998
Column: X-bridge C18, 3.5 μ, diameter 4.6 mm × 100 mm, (30 ° C.)
Carrier: (A) 2 mM-NH 4 OAc aq. (0.05% V / V Formula acid), (B) MeOH
Gradient: 5% V / V MeOH (1 min), MeOH 5% V / V → 95% V / V (1-15 min), 95% V / V MeOH (15-18 min)
Detector: UV300nm
反応終了後、反応混合物に水　１０ｍｌ及び１０％（Ｗ／Ｗ）塩酸　２．４ｇを加えることにより、過剰のナトリウムメトキシドを中和した。反応混合物中のエタノールを減圧下に留去したところ褐色のオイル状物が分離された。このオイル状物を含む残渣に酢酸エチル　１０ｍｌを加え、５０ｍｌ容量の分液ロートに移した。水層のｐＨは約４．０であった。 After completion of the reaction, excess sodium methoxide was neutralized by adding 10 ml of water and 2.4 g of 10% (W / W) hydrochloric acid to the reaction mixture. When ethanol in the reaction mixture was distilled off under reduced pressure, a brown oily substance was separated. To the residue containing this oily substance, 10 ml of ethyl acetate was added, and the residue was transferred to a 50 ml separatory funnel. The pH of the aqueous layer was about 4.0.
酢酸エチル層を分離して水　５ｍｌで洗浄した。洗浄後の酢酸エチル層をエバポレーターに移し、減圧下に酢酸エチルを留去した。粗製状態のグアイアシルビニルケトン　１．２２ｇ（収率１０４％）が淡褐色のオイル状物として得られた。ＨＰＬＣ純度は９３％であった。 The ethyl acetate layer was separated and washed with 5 ml of water. The washed ethyl acetate layer was transferred to an evaporator, and ethyl acetate was distilled off under reduced pressure. 1.22 g (yield 104%) of guaiacyl vinyl ketone in a crude state was obtained as a light brown oil. The HPLC purity was 93%.
粗製グアイアシルビニルケトンの全量を以下のようにカラム処理して精製した。
ワコーゲルＣ２００を内径２１ｍｍのガラスカラムに１００ｍｍ充填し、トルエンを供給した。充填剤がトルエンで満たされた後、ここに粗製グアイアシルビニルケトンをトルエン　６ｍｌに溶解して供給した。トルエンを溶媒として展開し、２０ｍｌずつのフラクションを採取した。目的物の含有されているフラクションを、薄層クロマトグラフで確認して回収した後、エバポレーターで減圧下にトルエンを留去したところ、精製されたグアイアシルビニルケトン　０．７５ｇを得た。精製収率は６１％であり、ＨＰＬＣ純度は９９％であった。 The total amount of crude guaiacyl vinyl ketone was purified by column treatment as follows.
Wako Gel C200 was packed 100 mm in a glass column having an inner diameter of 21 mm, and toluene was supplied. After the filler was filled with toluene, crude guaiacyl vinyl ketone was dissolved in 6 ml of toluene and supplied. Toluene was used as a solvent, and 20 ml fractions were collected. The fraction containing the desired product was confirmed by thin-layer chromatography and collected, and then toluene was distilled off under reduced pressure by an evaporator to obtain 0.75 g of purified guaiacyl vinyl ketone. The purification yield was 61% and the HPLC purity was 99%.
得られた精製グアイアシルビニルケトンを、以下の条件の逆相ＵＰＬＣ－飛行時間型精密質量分析（ＡＣＣＵＩＴＹ　ＵＰＬＣ　Ｈ－Ｃｌａｓｓ，ＸｅｖｏＧ２　ＱＴＯＦ；ウォーターズ社製）にかけ、マススペクトルを測定したところ、１７７．０５５０の負イオンを検出した。これは目的物の分子量－１に相当する。 The obtained purified guaiacyl vinyl ketone was subjected to reversed-phase UPLC-time-of-flight accurate mass spectrometry (ACCUITY UPLC H-Class, XevoG2 QTOF; manufactured by Waters) under the following conditions, and the mass spectrum was measured. Negative ions were detected. This corresponds to the molecular weight of the target product-1.
逆相ＵＰＬＣ条件
カラム；ＡＣＱＵＩＴＹ　ＵＰＬＣ　ＨＳＳ　Ｔ３　Ｃ１８　Ｃｏｌｕｍｎ，１．８μｍ、２．１ｍｍ　ｘ　１００ｍｍ（ウォーターズ社製）、
溶離液；（Ａ）［２ｍＭ　酢酸アンモニウム、０．０５％Ｖ／Ｖ　ギ酸］、（Ｂ）メタノール、
送液：溶離液（Ｂ）０－５分　５％Ｖ／Ｖ－９５％Ｖ／Ｖ；溶離液（Ｂ）５－７分　９５％Ｖ／Ｖ、
カラム温度；４０℃、流速；０．４ｍｌ／ｍｉｎ Reversed phase UPLC condition column; ACQUITY UPLC HSS T3 C18 Column, 1.8 μm, 2.1 mm × 100 mm (manufactured by Waters),
Eluent: (A) [2 mM ammonium acetate, 0.05% V / V formic acid], (B) methanol,
Solution: Eluent (B) 0-5 minutes 5% V / V-95% V / V; Eluent (B) 5-7 minutes 95% V / V,
Column temperature: 40 ° C., flow rate: 0.4 ml / min
質量分析条件
検出質量範囲１００－１０００Ｄａ、データ取得スキャン間隔０．１秒、デソルベーションガス温度　５００℃、イオンソース　ＥＳＩネガティブモード　イオンソース温度１５０℃、コーン電圧２０Ｖ Mass analysis condition detection mass range 100-1000 Da, data acquisition scan interval 0.1 second, desolvation gas temperature 500 ° C., ion source ESI negative mode ion source temperature 150 ° C., cone voltage 20V
次に、精製グアイアシルビニルケトンを、４００ＭＨｚの核磁気共鳴吸収装置に供して測定したＮＭＲスペクトルの結果及び帰属を示す。これらの測定結果は測定対象物がグアイアシルビニルケトンの構造を有することを支持する。 Next, the result and attribution of the NMR spectrum measured by using the purified guaiacyl vinyl ketone in a 400 MHz nuclear magnetic resonance absorber are shown. These measurement results support that the measurement object has a structure of guaiacyl vinyl ketone.
１Ｈ－ＮＭＲ測定結果（ＣＤ３ＣＯＣＤ３溶媒）
３．９３ｐｐｍ（ｓ，３Ｈ）－ＯＣＨ３
５．８５ｐｐｍ（ｄｄ，１Ｈ，Ｊ＝１０．４Ｈｚ，Ｊ＝２Ｈｚ）　Ｃ＝ＣＨ２
６．３５ｐｐｍ（ｄｄ，１Ｈ，Ｊ＝１６．８Ｈｚ，Ｊ＝２Ｈｚ）　Ｃ＝ＣＨ２
６．９５ｐｐｍ（ｄ，１Ｈ，Ｊ＝８．４Ｈｚ）芳香族－Ｈ（５位）
７．３９ｐｐｍ（ｄｄ，１Ｈ，Ｊ＝１６．８Ｈｚ，Ｊ＝１０．４Ｈｚ）－ＣＨ－
７．６１ｐｐｍ（ｄ，１Ｈ，Ｊ＝２Ｈｚ）芳香族－Ｈ（２位）
７．６４ｐｐｍ（ｄｄ，１Ｈ，Ｊ＝８．４Ｈｚ，Ｊ＝２Ｈｚ）芳香族－Ｈ（６位） 1H-NMR measurement results (CD3COCD3 solvent)
3.93 ppm (s, 3H) -OCH3
5.85 ppm (dd, 1H, J = 10.4 Hz, J = 2 Hz) C = CH 2
6.35 ppm (dd, 1H, J = 16.8 Hz, J = 2 Hz) C = CH 2
6.95 ppm (d, 1H, J = 8.4 Hz) aromatic-H (5th position)
7.39 ppm (dd, 1H, J = 16.8 Hz, J = 10.4 Hz) -CH-
7.61 ppm (d, 1H, J = 2Hz) Aromatic-H (2nd position)
7.64 ppm (dd, 1H, J = 8.4 Hz, J = 2 Hz) Aromatic-H (6th)
［実施例２］
２５ｍｌの水を加えた５０ｍｌの三角フラスコに、３－クロロ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノン　０．６１ｇ（０．００２８４モル）を室温で撹拌しながら溶解させた。この溶液に、１Ｍ－ＮａＯＨ水溶液　５．６９ｇ（０．００５６９モル）を室温で徐々に加えたところ、黄色の均一な反応液を得た。この反応液を、室温で０．５時間及び６５℃で１時間反応させた。原料のピークが消失したことを実施例１に記載の条件で実施したＨＰＬＣにより確認した。 [Example 2]
In a 50 ml Erlenmeyer flask containing 25 ml of water, 0.61 g (0.00284 mol) of 3-chloro-1- (4-hydroxy-3-methoxyphenyl) -1-propanone was dissolved with stirring at room temperature. . To this solution, 5.69 g (0.00569 mol) of 1M NaOH aqueous solution was gradually added at room temperature to obtain a yellow uniform reaction solution. This reaction solution was reacted at room temperature for 0.5 hour and at 65 ° C. for 1 hour. The disappearance of the peak of the raw material was confirmed by HPLC carried out under the conditions described in Example 1.
上記反応の終了後、反応液を室温まで冷却し、さらに１０％（Ｗ／Ｗ）塩酸　１．０６ｇ（０．００２９０モル）で中和してｐＨを約５としたところ、水溶媒の中に褐色のオイル状物が分離した。ここに、酢酸エチル　１０ｍｌを加えて、５０ｍｌ容量の分液ロートに移し酢酸エチル層を採取した。さらに水層を酢酸エチル　１０ｍｌで抽出し、計２回抽出を行った。抽出液を水　５ｍｌで洗浄し、酢酸エチル層から揮発分をエバポレーターで減圧下に留去したところ、淡褐色のオイル状のグアイアシルビニルケトン　０．５１ｇ（収率１００％）が得られた。ＨＰＬＣによる純度は９７％であった。不純物として２％の３－ヒドロキシ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンを含んでいた。 After completion of the above reaction, the reaction solution was cooled to room temperature and further neutralized with 1.06 g (0.00290 mol) of 10% (W / W) hydrochloric acid to adjust the pH to about 5. A brown oil separated. To this, 10 ml of ethyl acetate was added and transferred to a separating funnel having a capacity of 50 ml, and an ethyl acetate layer was collected. Further, the aqueous layer was extracted with 10 ml of ethyl acetate and extracted twice in total. The extract was washed with 5 ml of water, and volatile components were distilled off from the ethyl acetate layer under reduced pressure using an evaporator. As a result, 0.51 g (yield 100%) of a light brown oily guaiacyl vinyl ketone was obtained. The purity by HPLC was 97%. It contained 2% 3-hydroxy-1- (4-hydroxy-3-methoxyphenyl) -1-propanone as an impurity.
［参考例１］
５ｍｌ容量の試験管に、モノマー成分として実施例２で得られたグアイアシルビニルケトン　０．１６ｇ（０．０００９０モル）と、溶媒としてモレキュラーシブス３Ａで２日間乾燥したテトラヒドロフラン　１ｇと、ラジカル開始剤としてアゾビスイソブチロニトリル　７ｍｇとを加えた。この試験管をシリコンゴム栓で封じた後、窒素置換した。この試験管を６０℃のシリコンオイルバスに浸けて、４４．５時間反応させた。反応後、試験管中の反応混合物から、減圧下に溶媒を留去したところ、フラスコ壁に膜状物が付着した。この膜状物の重量は０．１５ｇであり、収率は９４％であった。この膜状物を機械的に掻きとると白色粉末となった。 [Reference Example 1]
In a test tube having a capacity of 5 ml, 0.16 g (0.00090 mol) of guaiacyl vinyl ketone obtained in Example 2 as a monomer component, 1 g of tetrahydrofuran dried with Molecular Sieves 3A as a solvent for 2 days, and a radical initiator As a solution, 7 mg of azobisisobutyronitrile was added. The test tube was sealed with a silicone rubber stopper and then purged with nitrogen. This test tube was immersed in a 60 ° C. silicone oil bath and allowed to react for 44.5 hours. After the reaction, when the solvent was distilled off from the reaction mixture in the test tube under reduced pressure, a film-like substance adhered to the flask wall. The weight of this film was 0.15 g, and the yield was 94%. When this film was mechanically scraped, a white powder was obtained.
この白色粉末は、メタノール、テトラヒドロフラン、アセトンなどに溶解し、クロロフォルムには溶解しなかった。この粉末をテトラヒドロフラン溶液として試験管に入れ、溶媒を留去することによって透明の膜が形成した（図１を参照）。また、この透明の膜は、希薄な苛性ソーダ水溶液に溶解することができた。 This white powder was dissolved in methanol, tetrahydrofuran, acetone, etc., but not in chloroform. This powder was placed in a test tube as a tetrahydrofuran solution, and the solvent was distilled off to form a transparent film (see FIG. 1). Further, this transparent film could be dissolved in a dilute caustic soda aqueous solution.
上記白色粉末をプロトンＮＭＲ（ＣＤ３ＣＯＣＤ３溶媒）に供したところ、グアイアシルビニルケトンのスペクトルで見られる５．８５ｐｐｍ及び６．３５ｐｐｍの二重結合に基づく吸収が消失し、高分子のメチンプロトンとメチレンプロトンにそれぞれ帰属される３．０ｐｐｍ付近と１．９ｐｐｍ付近に新しい吸収が認められた。 When the white powder was subjected to proton NMR (CD3COCD3 solvent), the absorption based on the double bonds of 5.85 ppm and 6.35 ppm seen in the spectrum of guaiacyl vinyl ketone disappeared, and the methine proton and methylene proton of the polymer disappeared. New absorptions were observed around 3.0 ppm and 1.9 ppm, respectively.
上記白色粉末の高分子は、アルカリ水溶液に溶解したのち、塩酸などの酸性物質で中和して沈殿させ、濾過水洗することにより精製品を得ることができた。 The white powder polymer was dissolved in an alkaline aqueous solution, neutralized with an acidic substance such as hydrochloric acid, precipitated, and washed with filtered water to obtain a purified product.
本発明の製造方法は、リグニンの微生物分解などにより得られる、３－ヒドロキシ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンから、３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンを経由して、工業的規模で高純度のグアイアシルビニルケトンを製造する効率の良い方法である。グアイアシルビニルケトンは高分子を製造する際のモノマー成分とすることができ、さらにレジストなどの光感受性組成物の製造用原料として有用である。したがって、本発明の製造方法は、産業上有用なグアイアシルビニルケトンを、工業的規模での製造を可能とする方法である。 The production method of the present invention comprises 3-halogen-1- (4-hydroxy-3) from 3-hydroxy-1- (4-hydroxy-3-methoxyphenyl) -1-propanone obtained by microbial degradation of lignin and the like. It is an efficient method for producing high-purity guaiacyl vinyl ketone on an industrial scale via -methoxyphenyl) -1-propanone. Guaacyl vinyl ketone can be used as a monomer component in producing a polymer, and is further useful as a raw material for producing a photosensitive composition such as a resist. Therefore, the production method of the present invention is a method that enables production of industrially useful guaiacyl vinyl ketone on an industrial scale.

Claims (5)

  1. 溶媒中で、下記一般式（１）
    Figure JPOXMLDOC01-appb-C000001
     　　　　（１）
    （式中、Ｘはハロゲン原子を示す。）
    で表わされる３－ハロゲノ－１－(４－ヒドロキシ－３－メトキシフェニル)－１－プロパノンと塩基性物質とを接触させることにより、グアイアシルビニルケトンを得る工程
    を含む、グアイアシルビニルケトンの製造方法。     In the solvent, the following general formula (1)
    Figure JPOXMLDOC01-appb-C000001
     (1)
    (In the formula, X represents a halogen atom.)
    The production of guaiacyl vinyl ketone, comprising the step of obtaining guaiacyl vinyl ketone by contacting 3-halogeno-1- (4-hydroxy-3-methoxyphenyl) -1-propanone represented by the formula: Method.
  2. 前記ハロゲン原子が塩素原子又は臭素原子である、請求項１に記載のグアイアシルビニルケトンの製造方法。 The method for producing a guaiacyl vinyl ketone according to claim 1, wherein the halogen atom is a chlorine atom or a bromine atom.
  3. 前記溶媒がアルコール類又は水である、請求項１に記載のグアイアシルビニルケトンの製造方法。 The manufacturing method of the guaiacyl vinyl ketone of Claim 1 whose said solvent is alcohol or water.
  4. 前記塩基性物質が、アルカリ金属の水酸化物、アルカリ金属の炭酸塩、アルカリ金属の重炭酸塩及びアルカリ金属のアルコキシドからなる群から選ばれる塩基性物質である、請求項１に記載のグアイアシルビニルケトンの製造方法。 The guaiacyl according to claim 1, wherein the basic substance is a basic substance selected from the group consisting of alkali metal hydroxides, alkali metal carbonates, alkali metal bicarbonates, and alkali metal alkoxides. A method for producing vinyl ketone.
  5. 前記溶媒が水であり、かつ、前記塩基性物質がアルカリ金属の水酸化物、アルカリ金属の炭酸塩及びアルカリ金属の重炭酸塩からなる群から選ばれる塩基性物質である、請求項１に記載のグアイアシルビニルケトンの製造方法。 2. The solvent according to claim 1, wherein the solvent is water, and the basic substance is a basic substance selected from the group consisting of alkali metal hydroxides, alkali metal carbonates, and alkali metal bicarbonates. Process for producing guaiacyl vinyl ketone.
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* Cited by examiner, † Cited by third party
Title
COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS, vol. 47, no. 3, 1982, pages 908 - 911 *
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 70, 1948, pages 60 - 63 *
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