Method for producing oxystyrene compound having multiple ether substituents

Abstract

To provide a method for producing an oxystyrene compound having a plurality of ether substituents in an inexpensive and convenient process.SOLUTION: The present invention provides a method for producing an oxystyrene derivative represented by formula (3), by reacting an aromatic halogen compound with magnesium metal, in the presence of an amine, to give a compound represented by formula (2), which is then reacted with a vinyl halide in the presence of a transition metal catalyst.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a novel method for producing an oxystyrene compound having multiple ether-type substituents, and more specifically, to a method for producing an oxystyrene compound by preparing an organometallic compound from an aryl halide having multiple ether-type substituents and subjecting the organometallic compound to a cross-coupling reaction with a vinyl halide. [Background technology]

[0002] Hydroxystyrene and other oxystyrene-based polymers are used as functional polymer materials in various industrial fields. For example, they are used in the field of electronic materials, particularly as raw materials for semiconductor resist resin components. They are also being considered for use as photosensitive resin components for interlayer insulating films and surface protective films for semiconductor elements and the like.

[0003] Therefore, there is a need to develop a method for producing a high-purity oxystyrene compound, which is a raw material for oxystyrene polymers. To solve this problem, a method for producing oxystyrene polymers by a cross-coupling reaction using aryl halides as raw materials has been proposed. For example, Patent Document 1 proposes a method for producing p-(1-ethoxyethoxy)styrene by preparing a Grignard reagent from p-(1-ethoxyethoxy)bromobenzene and metallic magnesium, and then carrying out a cross-coupling reaction with vinyl bromide in the presence of a nickel catalyst. Furthermore, Patent Document 2 proposes a method for producing a polysubstituted oxystyrene compound by reacting an aromatic halogen compound with a lithium chloride complex of isopropyl magnesium chloride, known as a turbo Grignard reagent, in the presence of an acyclic aliphatic amine compound, and then reacting the resulting reaction product with vinyl chloride in the presence of a nickel catalyst. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Publication No. 6-194842 [Patent Document 2] Patent Publication No. 2021-38196 Summary of the Invention [Problem to be solved by the invention]

[0005] When the present inventors attempted to synthesize an oxystyrene having multiple ether-type substituents by using the production method described in Patent Document 1, the reaction between the Grignard compound and the solvent mainly proceeded, making it difficult to obtain the target compound. In addition, the turbo Grignard reagent used in the production method described in Patent Document 2 is expensive, and there is a problem that a compound having an isopropyl group derived from the turbo Grignard reagent instead of a vinyl group is produced as a by-product in the cross-coupling reaction. This by-product is difficult to separate from the target oxystyrene compound, so it is necessary to suppress the by-product. In addition, this method also has the problem of requiring a large amount of solvent.

[0006] Therefore, the present invention has been made in consideration of the above-mentioned background art, and an object of the present invention is to provide a polysubstituted oxystyrene compound by a method that is more economical and simpler than the conventionally known production methods. [Means for solving the problem]

[0007] In order to solve the above problems, the present inventors have discovered that by using metallic magnesium and a tertiary amine in the process of Grignard conversion of an aromatic halogen compound, it is possible to economically produce a polysubstituted oxystyrene on an industrial scale, and have thus completed the present invention. That is, the present invention relates to the following. [1] The following general formula (1) [ka] (In formula (1), R 1 and R 2each independently represents an acid labile group, and X represents a chlorine atom, a bromine atom, or an iodine atom. and metallic magnesium in the presence of a tertiary amine to obtain an aromatic halide represented by the following general formula (2): [ka] (In formula (2), R 1 and R 2 each independently represents an acid labile group, and X represents a chlorine atom, a bromine atom, or an iodine atom. Then, the compound represented by the general formula (2) is reacted with a vinyl halide in the presence of a transition metal catalyst to obtain a compound represented by the following general formula (3): [ka] (In formula (3), R 1 and R 2 each independently represents an acid labile group. A method for producing an oxystyrene derivative represented by the formula: [2] The production method according to [1], wherein the transition metal contained in the transition metal catalyst is at least one selected from the group consisting of iron, cobalt, manganese, nickel, palladium and rhodium. [3] The method according to [1], wherein the transition metal contained in the transition metal catalyst is iron and / or nickel. [4] The process according to any one of [1] to [3], wherein the tertiary amine is an aliphatic tertiary amine. [5] The method according to any one of [1] to [4], wherein the vinyl halide is vinyl chloride and / or vinyl bromide. In the general formula (1) described in [6][1], R 1 and R 2 Each independently represents the following general formula (4): [ka] (In formula (4), R 3 and R 4each independently represents a hydrogen atom or a hydrocarbon group having 1 to 12 carbon atoms; R 5 represents a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms; or R 3 Or R 4 and R 5 and R are bonded to form a ring structure having 3 to 20 carbon atoms, which may contain an oxygen atom in the ring. 5 R does not combine with 3 Or R 4 represents a hydrogen atom or a hydrocarbon group having 1 to 12 carbon atoms, * indicates the bond position with the oxygen atom.) The method according to any one of [1] to [5], wherein the group is represented by the following formula: In the general formula (1) described in [7][1], R 1 and R 2 are each independently a 1-methoxyethyl group, a 1-ethoxyethyl group, a 1-iso-propoxyethyl group, a 1-n-butoxyethyl group, a 1-tert-butoxyethyl group, a methoxymethyl group, an ethoxymethyl group, an iso-propoxymethyl group, an n-butoxymethyl group, a tert-butoxymethyl group, a tetrahydropyranyl group, a tetrahydrofuranyl group, a 1-cyclohexyloxyethyl group, a (2-adamantyl)oxymethyl group, or a 1-(1-adamantyl)oxyethyl group. In the general formula (1) described in [8][1], R 1 and R 2 are each independently a 1-ethoxyethyl group. Effect of the Invention

[0008] As described above, according to the present invention, it is possible to efficiently produce the target oxystyrene compound having a plurality of ether-type substituents while suppressing side reactions in a cheaper and simpler method as compared with the conventional method. [Brief description of the drawings]

[0009] [Figure 1] GC measurement chart of the compound produced in Example 1, where the X-axis (horizontal axis) indicates retention time (unit: min), and the Y-axis (vertical axis) indicates relative peak intensity (unit: arbitrary). Numbers in the figure indicate peak retention time (unit: min). [Diagram 2] FIG. 2 is an enlarged view of FIG. [Diagram 3] GC measurement chart of the compound produced in Comparative Example 2, where the X-axis (horizontal axis) indicates retention time (unit: min), and the Y-axis (vertical axis) indicates relative peak intensity (unit: arbitrary). Numbers in the figure indicate peak retention time (unit: min). [Figure 4] FIG. 4 is an enlarged view of FIG. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] In this specification, the process of reacting an aromatic halogen compound represented by the above general formula (1) with metallic magnesium in the presence of an amine to obtain a compound represented by the above general formula (2) is defined as a Grignard process or Grignard reaction. Furthermore, the process of reacting the compound represented by the above general formula (2) with a vinyl halide in the presence of a transition metal catalyst to obtain an oxystyrene derivative represented by the above general formula (3) is defined as a cross-coupling process or a cross-coupling reaction.

[0011] In the above general formula (1), R 1 O groups and R 2 The O group is bonded to the R 1 O groups and R 2 Each O group may be in the ortho, meta, or para position relative to the group represented by X. In the above general formula (2), R 1 O groups and R 2 The O group is bonded to the R 1 O groups and R2 Each O group may be in the ortho, meta, or para position relative to the group represented by MgX. In the above general formula (3), R 1 O groups and R 2 The O group is bonded to the R 1 O groups and R 2 Each O group may be in the ortho, meta or para position relative to the vinyl group.

[0012] R 1 and R 2 The acid labile group of R 1 and R 2 When a group represented by the following formula (I) is eliminated, a hydroxy group is formed. In the above general formula (4), R 3 and R 4 each independently represents a hydrogen atom or a hydrocarbon group having 1 to 12 carbon atoms; R 5 represents a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms. 3 Or R 4 and R 5 and R are bonded to form a ring structure having 3 to 20 carbon atoms, which may contain an oxygen atom in the ring. 5 R does not combine with 3 Or R 4 , i.e. R 5 R 3 R when combining with 4 and R 5 R 4 R when combining with 3 In this case, R 3 Or R 4 represents a hydrogen atom or a hydrocarbon group having 1 to 12 carbon atoms. In the above general formula (4), "*" indicates the bonding position with the oxygen atom. That is, the structure of general formula (4) is the same as that of general formula (1) above, R 1 O groups and / or R 2 In the O group, R 1 O, R 2 This means the position where the 'O' of O is bonded. Specific examples of the acid labile group include 1-methoxyethyl group, 1-ethoxyethyl group, 1-iso-propoxyethyl group, 1-n-butoxyethyl group, 1-tert-butoxyethyl group, methoxymethyl group, ethoxymethyl group, iso-propoxymethyl group, n-butoxymethyl group, tert-butoxymethyl group, tetrahydropyranyl group, tetrahydrofuranyl group, 1-cyclohexyloxyethyl group, (2-adamantyl)oxymethyl group, 1-(1-adamantyl)oxyethyl group, etc. Among these, the 1-ethoxyethyl group is particularly preferred.

[0013] The metallic magnesium used in the method of the present invention may be any known form of magnesium commonly used in Grignard reactions, such as powder, flakes, granules, chips, lumps, and chips. The amount of metallic magnesium used may be 1.0 times or more by mole relative to the aromatic halogen compound represented by the general formula (1), and from the economical point of view and ease of post-treatment, the amount is preferably in the range of 1.0 to 2.0 times by mole, and more preferably in the range of 1.0 to 1.4 times by mole.

[0014] In the present invention, particularly good results can be obtained when activated metallic magnesium is used. There is no particular limitation on the method for activating metallic magnesium. Effective methods include, but are not limited to, a method of heating and stirring metallic magnesium suspended in a solvent, and a method of adding a small amount of iodine, an iodide such as methyl iodide, or a bromide such as bromoethane or dibromoethane to the suspension and stirring the mixture. There is no particular limitation on the amount of iodide or bromide to be added, but the amount is selected from the range of 0.01 to 0.5 times the molar amount relative to metallic magnesium.

[0015] The tertiary amine used in the present invention is preferably an aliphatic tertiary amine. Specific examples include trimethylamine, triethylamine, N,N-diisopropylethylamine, N,N-dimethylcyclohexylamine, N,N,N',N'',N''-pentamethyldiethylenetriamine, N,N,N',N'-tetramethylethylenediamine, N,N,N',N'-tetramethylpropylenediamine, N,N,N',N'-tetramethylhexamethylenediamine, N,N,N',N'',N''',N'''-hexamethyltriethylenetetramine, and the like. Among these, trimethylamine, triethylamine, N,N-dimethylcyclohexylamine, and N,N,N',N'-tetramethylethylenediamine are preferably used in terms of achieving both reactivity and selectivity in the Grignard reaction and the cross-coupling reaction, and N,N,N',N'-tetramethylethylenediamine is more preferably used. The amount of the amine used may be 1.0 times or more by mole relative to the aromatic halogen compound represented by the above general formula (1).Furthermore, from the economical point of view and the possibility that the amine coordinates with the metal catalyst and the reactivity of the cross-coupling reaction decreases, the amount is preferably in the range of 1.0 to 3.0 times by mole, and more preferably in the range of 1.0 to 2.0 times by mole.

[0016] The vinyl halides used in the method of the present invention are vinyl fluoride, vinyl chloride, vinyl bromide, and vinyl iodide, which can be used alone or in mixtures. Among these, vinyl chloride and / or vinyl bromide are usually selected in consideration of reactivity, economy, and availability. The amount of vinyl halide used may be 1.0 times or more by mole relative to the aromatic halogen compound represented by the above general formula (1), and is preferably 1.4 times or less by mole in consideration of economic efficiency and the complication of post-treatment steps.

[0017] As the transition metal catalyst used in the process of the present invention, it is particularly effective to use a catalyst containing at least one metal selected from the group consisting of iron, cobalt, manganese, nickel, palladium and rhodium.

[0018] In the present invention, examples of the catalyst containing iron include compounds such as iron chloride (II), iron chloride (III), iron bromide (II), iron bromide (III), iron iodide (II), iron iodide (III), iron fluoride (II), iron fluoride (III), iron acetate (II), iron oxalate (II), iron oxalate (III), iron citrate (III), iron perchlorate (III), iron (III) acetylacetonate, iron nitrate (III), iron phosphate (III), iron sulfate (II), and iron sulfate (III), as well as iron powders, hydrates of these compounds, and various complex catalysts derived from these compounds.

[0019] In the present invention, examples of the catalyst containing cobalt include compounds such as cobalt chloride (II), cobalt bromide (II), cobalt iodide (II), cobalt fluoride (II), cobalt acetate (II), cobalt acetate (III), cobalt formate (II), cobalt oxalate (II), cobalt benzoate (II), cobalt stearate (II), cobalt borate (II), cobalt (II) acetylacetonate, cobalt carbonate (II), cobalt sulfate (II), cobalt nitrate (II), and cobalt phosphate (II), as well as cobalt powder, hydrates of these compounds, and various complex catalysts derived from these compounds.

[0020] In the present invention, examples of the catalyst containing manganese include manganese chloride (II), manganese bromide (II), manganese iodide (II), manganese fluoride (II), manganese acetate (II), manganese acetate (III), manganese formate (II), manganese oxalate (II), manganese benzoate (II), manganese stearate (II), manganese borate (II), manganese (II) acetylacetonate, manganese (III) acetylacetonate, manganese carbonate (II), manganese sulfate (II), manganese nitrate (II), manganese phosphate (II), and other compounds, manganese powder, hydrates of these compounds, and various complex catalysts derived from these compounds.

[0021] In the present invention, examples of the nickel-containing catalyst include compounds such as nickel(II) chloride, nickel(II) bromide, nickel(II) iodide, nickel(II) fluoride, nickel(II) acetate, and nickel(II) acetylacetonate, nickel powder, hydrates of these compounds, and various complex catalysts derived from these compounds.

[0022] In the present invention, examples of the catalyst containing palladium include compounds such as palladium(II) chloride, palladium(II) bromide, palladium(II) acetate, and palladium(II) acetylacetonate, palladium powder, hydrates of these compounds, and various complex catalysts derived from these compounds.

[0023] In the present invention, examples of the catalyst containing rhodium include compounds such as rhodium(II) chloride, rhodium(II) bromide, rhodium(II) acetate, rhodium(III) acetate, rhodium(II) acetylacetonate, and rhodium(III) acetylacetonate, as well as rhodium powder, rhodium-carbon, hydrates of these compounds, and various complex catalysts derived from these compounds.

[0024] In addition, various ligands may be used in combination, and the method of adding the ligand may include a method of reacting the above-mentioned transition metal compound with the ligand outside the system beforehand and then adding it, or a method of adding the above-mentioned transition metal compound and the ligand to the reaction system and preparing it in the system. As the ligand, any one that coordinates with the above-mentioned transition metal compound may be used, and phosphorus-based compounds, nitrogen-based compounds, olefin-based compounds, etc. are selected. In particular, phosphorus-based compounds are preferred as the ligand. Specific examples of the ligand include 1,2-bis(diphenylphosphino)ethane [dppe], 1,3-bis(diphenylphosphino)propane [dppp], 1,4-bis(diphenylphosphino)butane [dppb], triphenylphosphine, 1,1'-bis(diphenylphosphino)ferrocene [dppf], 1,1'-bis(dicyclohexylphosphino)ferrocene, 2,2'-bis(diphenylphosphino)-1,1-binaphthyl [BINAP], bis(2-diphenylphosphinophenyl)ether [DPEphos], 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene [XANTphos], tri-tert-butylphosphine, 1,5-cyclooctadiene [COD], and 2,2'-bipyridyl.

[0025] Specific examples of the complex catalyst include [1,3-bis(diphenylphosphino)propane]nickel(II) dichloride, [1,2-bis(diphenylphosphino)ethane]nickel(II) dichloride, bis(triphenylphosphine)nickel(II) dichloride, [1,3-bis(diphenylphosphino)propane]palladium(II) dichloride, [1,2-bis(diphenylphosphino)ethane]palladium(II) dichloride, bis(triphenylphosphine)palladium(II) dichloride, [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride, and [1,1'-bis(dicyclohexylphosphino)ferrocene]palladium(II) dichloride.

[0026] The amount of the transition metal catalyst used in the method of the present invention is not particularly limited, but is in the range of 0.001 mol% to 20.0 mol%, preferably 0.01 mol% to 10.0 mol%, and more preferably 0.01 mol% to 1.0 mol% relative to the aromatic halogen compound represented by the above general formula (1). The amount of the ligand used is not particularly limited, but is selected from the range of 0.5 to 10 times the molar amount relative to the transition metal compound.

[0027] The method of the present invention is usually carried out in a solvent under an inert gas atmosphere such as nitrogen and / or argon. The solvent used in the Grignard reaction and the subsequent cross-coupling reaction in the method of the present invention is not particularly limited, and examples thereof include ether solvents, oxygen-containing solvents, nitrogen-containing solvents, aromatic hydrocarbon solvents, and aliphatic hydrocarbon solvents. Ether solvents and aromatic hydrocarbon solvents are preferably used, and specific examples thereof include tetrahydrofuran, cyclopentyl methyl ether, diethyl ether, diisopropyl ether, dibutyl ether, 1,2-dimethoxyethane, 1,2-diethoxyethane, 1,4-dioxane, benzene, toluene, and xylene. The solvents may be used alone or in combination. Although there is no particular limitation on the amount of solvent used in the method of the present invention, the amount of solvent used during the Grignard reaction is in the range of 0.5 to 20.0 times by weight relative to the aromatic halogen compound represented by the above general formula (1), which is useful in that the amount of solvent used can be reduced to such an extent that the reaction can be carried out even with an amount of 1.0 or less by weight. In addition, the amount of solvent added during coupling is in the range of 0.5 to 20.0 times by weight relative to the aromatic halogen compound represented by the above general formula (1), which is useful in that the amount of solvent used is small.

[0028] The temperature of the Grignard reaction in the method of the present invention is in the range of -20°C to 70°C, and preferably in the range of 0°C to 40°C. The temperature of the coupling reaction is in the range of -40°C to 90°C, and preferably in the range of -20°C to 40°C. As an embodiment of the coupling reaction in the method of the present invention, the reaction may be carried out by adding a vinyl halide to a solution of the prepared Grignard reagent, or the reaction may be carried out by adding a Grignard reagent to a vinyl halide.

[0029] After the reaction is completed, the reaction solution is neutralized in a conventional manner, and then the organic layer is separated. The organic layer is then washed with water, the solvent is removed by distillation, and the desired oxystyrene derivative is obtained by conventional purification procedures such as distillation and recrystallization. EXAMPLES

[0030] Examples of the present invention are shown below, but the present invention is not to be construed as being limited to these examples.

[0031] The purity of the compound obtained by the cross-coupling reaction was analyzed by gas chromatography (GC) under the following conditions. Equipment: GC-2025 (Shimadzu Corporation) Column: Capillary column NB-5 (GL Sciences, Inc.) The yield was determined by nuclear magnetic resonance analysis under the following conditions. Equipment: AVANCE II 400 (BRUKER) Solvent: deuterated acetone Internal standard: 1,3,5-trimethoxybenzene

[0032] Synthesis Example 1 In a 200 mL four-neck flask equipped with a thermometer, 113.41 g (600 mmol) of 4-bromocatechol, 0.68 g (6.0 mmol) of trifluoroacetic acid, and 466.67 g of toluene were added at room temperature under a nitrogen atmosphere, and 103.84 g (1.44 mol) of ethyl vinyl ether was added dropwise over 3 hours at 25° C. The mixture was aged at the same temperature for 3 days. After the reaction was completed, the reaction solution was cooled to 10°C, and 137 g of 20% aqueous sodium hydroxide solution was added and stirred for 30 minutes. After separation, the solvent was distilled off under reduced pressure to obtain 198.07 g (yield 99%) of 3,4-bis(1-ethoxyethoxy)bromobenzene as a reddish brown liquid.

[0033] Example 1 Synthesis of 3,4-bis(1-ethoxyethoxy)styrene (hereinafter referred to as "Compound 1") In a 50 mL four-neck round-bottom flask equipped with a thermometer, 0.46 g (18.8 mmol) of metallic magnesium, 5.41 g of tetrahydrofuran, 0.10 g (0.90 mmol) of bromoethane, and 2.09 g (18.0 mmol) of N,N,N',N'-tetramethylethylenediamine were added at room temperature under a nitrogen atmosphere, and the mixture was cooled to 10°C with stirring, and 5.81 g (15.0 mmol) of 3,4-bis(1-ethoxyethoxy)bromobenzene obtained in Synthesis Example 1 was added dropwise at the same temperature over 30 minutes. After the addition, the mixture was aged at 10°C for 3 hours to obtain a Grignard reagent. To the Grignard reagent obtained by the above procedure, 0.053 g (0.10 mmol) of [1,3-bis(diphenylphosphino)propane]nickel(II) dichloride and 6.08 g of toluene were added, and the mixture was cooled to 0°C. Then, 1.03 g (16.5 mmol) of vinyl chloride gas was blown in over 30 minutes. After the reaction was completed, 15.0 g of 20% aqueous ammonium chloride solution was added to the reaction solution to dissolve the salt formed, and the organic layer was separated. The organic layer obtained was washed twice with 10.0 g of 2% aqueous sodium hydroxide solution, and the solvent was distilled off under reduced pressure.

[0034] The obtained compound was analyzed by nuclear magnetic resonance analysis and mass spectrometry, and as a result, the compound was confirmed to be 3,4-bis(1-ethoxyethoxy)styrene. The yield quantified by nuclear magnetic resonance analysis was 73%. When the obtained compound was analyzed by gas chromatography, 3,4-bis(1-ethoxyethoxy)benzenebutanol (hereinafter referred to as "compound 2"), which is a reaction product with the solvent, was not detected. That is, as can be seen from the GC charts shown in Figures 1 and 2, compound 1 was detected, but compound 2 was less than 0.1% in terms of GC peak area, and 1,2-bis(1-ethoxyethoxy)-4-(1-methylethyl)-benzene (hereinafter referred to as "compound 3") to which an isopropyl group derived from a turbo Grignard reagent was introduced was not detected. The results are shown in Table 1 together with other examples.

[0035] Example 2 Synthesis of 3,4-bis(1-ethoxyethoxy)styrene (Compound 1) The same procedure as in Example 1 was repeated except that N,N-dimethylcyclohexylamine was used instead of N,N,N',N'-tetramethylethylenediamine, the Grignard reagent was prepared at 20°C, and the maturation time was 18 hours. The results of analysis of the compounds obtained as described above are shown in Table 1.

[0036] Example 3 Synthesis of 3,4-bis(1-ethoxyethoxy)styrene (Compound 1) The same procedure as in Example 1 was repeated except that triethylamine was used instead of N,N,N',N'-tetramethylethylenediamine and the maturation time in the preparation of the Grignard reagent was extended to 22 hours. The results of analysis of the compounds obtained as described above are shown in Table 1.

[0037] Example 4 Synthesis of 3,4-bis(1-ethoxyethoxy)styrene (Compound 1) The same procedure as in Example 1 was repeated except that iron chloride (III) was used instead of [1,3-bis(diphenylphosphino)propane]nickel (II) dichloride in Example 1. The results of analysis of the compounds obtained as described above are shown in Table 1.

[0038] Comparative Example 1: No amine used The same procedure as in Example 1 was repeated, except that N,N,N',N'-tetramethylethylenediamine was not used, the Grignard reagent was prepared at 25°C, the maturation time was 18 hours, and vinyl chloride gas was blown in at 20°C. The compound obtained was analyzed by gas chromatography and found to contain 61% of compound 2. The results are shown in Table 1.

[0039] Comparative Example 2: When Turbo Grignard Reagent was Used In a 200mL four-necked round-bottom flask equipped with a thermometer, 5.81g (15.0mmol) of 3,4-bis(1-ethoxyethoxy)bromobenzene, 15.00g of tetrahydrofuran, and 3.12g (18.0mmol) of N,N,N',N'',N''-pentamethyldiethylenetriamine were added at room temperature under a nitrogen atmosphere, and cooled to 0°C with stirring. 17.13g (16.5mmol) of isopropylmagnesium chloride lithium chloride complex·tetrahydrofuran solution (concentration 14%) was added dropwise at the same temperature over 1 hour. After the dropwise addition, the mixture was aged at 10°C for 24 hours to obtain a Grignard reagent. To the Grignard reagent obtained by the above operation, 0.053 g (0.10 mmol) of [1,3-bis(diphenylphosphino)propane]nickel(II) dichloride and 10.00 g of toluene were added, and the temperature was raised to 15° C., and 1.03 g (16.5 mmol) of vinyl chloride gas was blown in over 30 minutes. After the reaction was completed, 40.0 g of 20% aqueous ammonium chloride solution was added to the reaction solution to dissolve the salt formed, and the organic layer was separated. The organic layer obtained was washed twice with 35.0 g of 2% aqueous sodium hydroxide solution, and the solvent was distilled off under reduced pressure. When the compound obtained as described above was analyzed by gas chromatography, it was found to contain 6% of 1,2-bis(1-ethoxyethoxy)-4-(1-methylethyl)-benzene (compound 3) to which an isopropyl group derived from a turbo Grignard reagent had been introduced. That is, as can be seen from the GC charts shown in Figures 3 and 4, compound 1 was detected. Furthermore, compound 2 was detected at 1% by GC peak area, and compound 3 was detected at 6%. The results are shown in Table 1 together with other examples.

[0040] The results of Examples 1 to 4 and Comparative Examples 1 and 2 are shown in Table 1. [Table 1]

[0041] As described above, the production method of the present invention can economically and simply synthesize the target compound 1. In addition, the production method of the present invention is useful in that it can suppress the by-production of compound 2, which is generated by a side reaction with the solvent, and compound 3, which is difficult to separate from compound 1. [Industrial Applicability]

[0042] The method for producing a polysubstituted oxystyrene compound of the present invention is capable of producing an oxystyrene compound having a plurality of ether substituents in an economical and simple process, and therefore the present invention is extremely useful industrially.

Claims

1. The following general formula (1) 【Chemistry 5】 (In formula (1), R １ and R ２ each independently represents an acid labile group, and X represents a chlorine atom, a bromine atom, or an iodine atom. and metallic magnesium in the presence of a tertiary amine to obtain an aromatic halide represented by the following general formula (2): 【Chemistry 6】 (In formula (2), R １ and R ２ each independently represents an acid labile group, and X represents a chlorine atom, a bromine atom, or an iodine atom; and then reacting the compound represented by the general formula (2) with a vinyl halide in the presence of a transition metal catalyst, 【Chemistry 7】 (In formula (3), R １ and R ２ each independently represents an acid labile group. A method for producing an oxystyrene derivative represented by the formula:

2. 2. The process according to claim 1, wherein the transition metal contained in the transition metal catalyst is at least one selected from the group consisting of iron, cobalt, manganese, nickel, palladium and rhodium.

3. The method according to claim 1 , wherein the transition metal contained in the transition metal catalyst is iron and / or nickel.

4. The process according to any one of claims 1 to 3, wherein the tertiary amine is an aliphatic tertiary amine.

5. The process according to any one of claims 1 to 4, characterized in that the vinyl halide is vinyl chloride and / or vinyl bromide.

6. In the general formula (1) according to claim 1, R １ and R ２ Each of them independently represents the following general formula (4): 【Chemistry 8】 (In formula (4), R ３ and R ４ each independently represents a hydrogen atom or a hydrocarbon group having 1 to 12 carbon atoms; R ５ represents a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms; or R ３ Or R ４ and R ５ and R are bonded to form a ring structure having 3 to 20 carbon atoms, which may contain an oxygen atom in the ring. ５ R does not bond with ３ Or R ４ represents a hydrogen atom or a hydrocarbon group having 1 to 12 carbon atoms, * indicates the bond position with the oxygen atom.) The method according to any one of claims 1 to 5, wherein the group is represented by:

7. In the general formula (1) according to claim 1, R １ and R ２ are each independently a 1-methoxyethyl group, a 1-ethoxyethyl group, a 1-iso-propoxyethyl group, a 1-n-butoxyethyl group, a 1-tert-butoxyethyl group, a methoxymethyl group, an ethoxymethyl group, an iso-propoxymethyl group, an n-butoxymethyl group, a tert-butoxymethyl group, a tetrahydropyranyl group, a tetrahydrofuranyl group, a 1-cyclohexyloxyethyl group, a (2-adamantyl)oxymethyl group, or a 1-(1-adamantyl)oxyethyl group.

8. In the general formula (1) according to claim 1, R １ and R ２ The method according to any one of claims 1 to 7, wherein each of the groups independently represents a 1-ethoxyethyl group.

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