Novel method for producing benzoxazine compounds

Abstract

The present invention addresses the problem of providing a production method having higher safety and efficiency in a method for producing a target benzoxazine compound that does not create a sudden temperature rise or smoke when introducing the raw material prior to benzoxazine compound generation. Provided as a solution is a method for producing a benzoxazine compound represented by general formula (3), characterized by mixing and reacting a mixture including a bisphenol compound represented by general formula (1) and formaldehydes with an amine compound represented by general formula (2). H2N-R4-Y (2)

Description

[Technical Field]

[0001] The present invention relates to a novel method for producing a benzoxazine compound, and more particularly to a novel method for producing a benzoxazine compound having benzoxazine rings at both ends of a bonding group and further having a hydroxy group or a thiol group. [Background technology]

[0002] Benzoxazine compounds are compounds synthesized by reacting phenols, amines, and formaldehyde, and are known as thermosetting resin raw materials that cure by ring-opening polymerization of the benzoxazine ring upon heating without producing volatile by-products, and are used as raw materials for molded articles that can be used as materials for insulating substrates, liquid crystal alignment agents, semiconductor encapsulation resin compositions, etc. For such applications, heat resistance with excellent stability and reliability at high temperatures is required. On the other hand, the curing temperature of benzoxazine compounds is usually relatively high, and in order to lower the polymerization temperature, catalysts, polymerization accelerators, and highly reactive benzoxazine compounds have been developed in recent years. Among these highly reactive benzoxazine compounds, a benzoxazine composition containing a hydroxy group or a nitrogen-containing heterocycle has been reported, which can be cured at a relatively low temperature in a short time by an environmentally friendly method (Patent Document 1). Known methods for synthesizing hydroxyl group-containing benzoxazine compounds include, for example, a method in which the raw materials bisphenol A, an alcoholamine monomer, and paraformaldehyde are mixed together with a solvent and reacted together (Patent Document 2), and a method in which a mixed solution of paraformaldehyde and ethanolamine is first prepared, and then a solution of bisphenol A is added and reacted (Non-Patent Document 1). Furthermore, these methods are performed at high temperatures of 90°C or higher, and it has been reported that the product yield is relatively high. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Special Publication No. 2011-530570 [Patent Document 2] Chinese Patent Application Publication No. 107573496 [Non-patent literature]

[0004] [Non-Patent Document 1] E. Gilbert. et. al. J. Polym. Res. 2018, Vol.25, p.114. Summary of the Invention [Problem to be solved by the invention]

[0005] The present inventors attempted to synthesize a benzoxazine compound having a hydroxy group by the above-mentioned conventionally known production method, and found that when the raw materials were mixed, the temperature of the mixed solution rose rapidly, smoke was generated inside the reactor, and the internal pressure rose. Considering industrial production as well as laboratory-level operations, a state in which the temperature rises rapidly and smoke is generated when the raw materials are charged should be avoided as much as possible because it causes inconveniences such as the ejection of components inside the reactor due to a sudden rise in the internal pressure of the reactor, and the energy and time required for heat control. The widely accepted mechanism for producing benzoxazine compounds is one that involves a first step in which amines react with formaldehydes to produce an intermediate compound having a hexahydrotriazine structure, and a second step in which this intermediate compound reacts with phenols and formaldehydes to produce a compound having a benzoxazine structure (see, for example, paragraph 0005 of JP 2017-537182 A). The present inventors speculated that the heat of reaction generated when the above-mentioned amines react with formaldehydes to produce intermediate compounds having a hexahydrotriazine structure is the cause of the phenomenon of a sudden rise in temperature and smoke generation when the raw materials are charged. An object of the present invention is to provide a method for producing a target benzoxazine compound, which is safer and more efficient, without causing a sudden rise in temperature or smoke when raw materials are charged before the benzoxazine compound is produced. [Means for solving the problem]

[0006] As a result of intensive research into solving the above-mentioned problems, the present inventors have found that the above-mentioned problems can be solved and the desired benzoxazine compound can be synthesized by changing the method of mixing raw materials, specifically by mixing a bisphenol compound with a formaldehyde and then mixing an amine, and have thus completed the present invention. No heat generation was observed during the mixing of the bisphenol compound and formaldehydes, and it was confirmed that the reaction to obtain the target benzoxazine compound proceeded when the amines were subsequently mixed.

[0007] The present invention is as follows. 1. A method for producing a benzoxazine compound represented by general formula (3), which comprises mixing a mixture containing a bisphenol compound represented by general formula (1) and formaldehydes with an amine compound represented by general formula (2) and reacting them. [ka] (In the formula, R1 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and X represents a single bond, an oxygen atom, a sulfur atom, a sulfonyl group, a carbonyl group, or a divalent group represented by general formula (1a) or (1b).) [ka] (In general formulas (1a) and (1b), R2 and R3 each independently represent hydrogen, an alkyl group having 1 to 10 carbon atoms, a halogenated alkyl group having 1 to 10 carbon atoms, or an aryl group having 6 to 12 carbon atoms; R2 and R3 may be bonded to each other to form a cycloalkylidene group having 5 to 20 carbon atoms as a whole; Ar1 ​​and Ar2 each independently represent an aryl group having 6 to 12 carbon atoms; and * indicates the bonding position.) [ka] (In the formula, R4 represents a divalent group having 1 to 10 carbon atoms, and Y represents a hydroxy group or a thiol group.) [ka] (In the formula, R1 and X represent the same groups as in general formula (1), and R4 and Y represent the same groups as in general formula (2).) [Effects of the Invention]

[0008] The method for producing a benzoxazine compound of the present invention is extremely useful because it is possible to easily obtain the target benzoxazine compound with higher safety and efficiency in industrial production without causing a sudden rise in temperature or smoke generation when raw materials are charged before the production of the benzoxazine compound. DETAILED DESCRIPTION OF THE INVENTION

[0009] <Method of producing the benzoxazine compound of the present invention> The method for producing a benzoxazine compound of the present invention is characterized by mixing a mixture containing a bisphenol compound represented by general formula (1) and formaldehydes with an amine compound represented by general formula (2) and reacting them to produce a benzoxazine compound represented by general formula (3) as the target compound. [ka] (In the formula, R1 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and X represents a single bond, an oxygen atom, a sulfur atom, a sulfonyl group, a carbonyl group, or a divalent group represented by general formula (1a) or (1b).) [ka] (In general formulas (1a) and (1b), R2 and R3 each independently represent hydrogen, an alkyl group having 1 to 10 carbon atoms, a halogenated alkyl group having 1 to 10 carbon atoms, or an aryl group having 6 to 12 carbon atoms; R2 and R3 may be bonded to each other to form a cycloalkylidene group having 5 to 20 carbon atoms as a whole; Ar1 ​​and Ar2 each independently represent an aryl group having 6 to 12 carbon atoms; and * indicates the bonding position.) [ka] (In the formula, R4 represents a divalent group having 1 to 10 carbon atoms, and Y represents a hydroxy group or a thiol group.) [ka] (In the formula, R1 and X represent the same groups as in general formula (1), and R4 and Y represent the same groups as in general formula (2).)

[0010] R1 in general formulas (1) and (3) is preferably a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, more preferably a hydrogen atom or an alkyl group having 1 carbon atom (methyl group), and particularly preferably a hydrogen atom. When R1 is not a hydrogen atom, the bonding position is preferably the ortho position of the hydroxy group in general formula (1) or the ortho position on the benzene ring relative to the oxygen atom of the benzoxazine ring in general formula (3). When X in general formulas (1) and (3) is general formula (1a), more preferred R2 and R3 are each independently hydrogen, an alkyl group having 1 to 6 carbon atoms, a halogenated alkyl group having 1 to 6 carbon atoms, or an aryl group having 6 to 12 carbon atoms, still more preferred are hydrogen, an alkyl group having 1 to 4 carbon atoms, a trifluoromethyl group, or an aryl group having 6 to 8 carbon atoms, and particularly preferred are hydrogen, an alkyl group having 1 to 4 carbon atoms, or a phenyl group. R2 and R3 may be bonded to each other to form a cycloalkylidene group having 5 to 20 carbon atoms as a whole. The cycloalkylidene group having 5 to 20 carbon atoms may contain an alkyl group as a branched chain. The cycloalkylidene group preferably has 5 to 15 carbon atoms, more preferably 6 to 12 carbon atoms, and particularly preferably 6 to 9 carbon atoms. Specific examples of the cycloalkylidene group include a cyclopentylidene group (5 carbon atoms), a cyclohexylidene group (6 carbon atoms), a 3-methylcyclohexylidene group (7 carbon atoms), a 4-methylcyclohexylidene group (7 carbon atoms), a 3,3,5-trimethylcyclohexylidene group (9 carbon atoms), a cycloheptylidene group (7 carbon atoms), a bicyclo[2.2.1]heptane-2,2-diyl group (7 carbon atoms), a 1,7,7-trimethylbicyclo[2.2.1]heptane-2,2-diyl group (10 carbon atoms), a 4,7,7-trimethylbicyclo[2.2.1]heptane-2,2-diyl group (10 carbon atoms), a tricyclo[5.2.1.0 2,6]decane-8,8-diyl group (10 carbon atoms), 2,2-adamantylidene group (10 carbon atoms), cyclododecanylidene group (12 carbon atoms), etc. Preferred are cyclohexylidene group (6 carbon atoms), 3-methylcyclohexylidene group (7 carbon atoms), 4-methylcyclohexylidene group (7 carbon atoms), 3,3,5-trimethylcyclohexylidene group (9 carbon atoms), and cyclododecanylidene group (12 carbon atoms), more preferred are cyclohexylidene group (6 carbon atoms), 3,3,5-trimethylcyclohexylidene group (9 carbon atoms), and cyclododecanylidene group (12 carbon atoms), and particularly preferred are cyclohexylidene group (6 carbon atoms) and 3,3,5-trimethylcyclohexylidene group (9 carbon atoms). When X in general formulas (1) and (3) is general formula (1b), Ar1 and Ar2 are preferably each independently a benzene ring or a naphthalene ring, and more preferably both Ar1 and Ar2 are benzene rings. For example, when both Ar1 and Ar2 are benzene rings, the group represented by general formula (1b) is a fluorenylidene group. The bonding position of X in general formula (3) to the two benzoxazine rings is preferably the ortho or para position on the benzene ring relative to the oxygen atom of the benzoxazine ring, and similarly, the bonding position of X on the benzene ring in general formula (1), which is the raw material, is preferably the ortho or para position relative to the hydroxy group.

[0011] R4 in general formulas (2) and (3) is a divalent group having 1 to 10 carbon atoms. Specific examples include linear or branched alkylene groups or alkylene groups containing a cyclic alkane having 1 to 10 carbon atoms, such as methylene, ethylene, propane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, cyclohexane-1,3-diyl, and cyclohexane-1,4-diyl; alkylidene groups having 1 to 10 carbon atoms, such as ethylidene, propylidene, isopropylidene, butylidene, cyclopentylidene, and cyclohexylidene; phenylene; and divalent groups having 1 to 10 carbon atoms containing a benzene ring, such as groups represented by the following formulas: [ka] (In the formula, * indicates the bonding position.) Among these, R4 is preferably a linear or branched alkylene group having 1 to 10 carbon atoms, an alkylene group containing a cyclic alkane, or an alkylidene group having 1 to 10 carbon atoms, more preferably a linear or branched alkylene group having 1 to 10 carbon atoms or an alkylene group containing a cyclic alkane, still more preferably a linear or branched alkylene group having 1 to 6 carbon atoms or an alkylene group containing a cyclic alkane, and particularly preferably a linear or branched alkylene group having 1 to 4 carbon atoms.

[0012] Specific examples of the benzoxazine compound represented by general formula (3), which is the target compound of the production method of the present invention, include compounds (p-1) to (p-6) having the following chemical structures. [ka]

[0013] <Starting material: bisphenol compound represented by general formula (1)> Specific examples of the bisphenol compound represented by general formula (1), which is one of the starting materials in the method for producing a benzoxazine compound of the present invention, include bisphenol F (bis(2-hydroxyphenyl)methane, 2-hydroxyphenyl-4-hydroxyphenylmethane, bis(4-hydroxyphenyl)methane), bisphenol E (1,1-bis(4-hydroxyphenyl)ethane), bisphenol A (2,2-bis(4-hydroxyphenyl)propane), bisphenol C (2,2-bis(4-hydroxy-3-methylphenyl)propane), 2,2-bis(4-hydroxyphenyl)-4-methylpentane, 4,4'-dihydroxybiphenyl, 4,4'-dihydroxy-3,3'-dimethylbiphenyl, bis(4-hydroxyphenyl)ether, 4,4'-dihydroxybenzophenone, Bisphenols that may be used include bisphenol A (1,3-bis(2-(4-hydroxyphenyl)-2-propyl)benzene), bisphenol B (1,1-bis(4-hydroxyphenyl)-3,3,5-trimethylcyclohexane), bisphenol TMC (1,1-bis(4-hydroxyphenyl)-3,3,5-trimethylcyclohexane), bisphenol B (1,1-bis(4-hydroxyphenyl)cyclododecane), bisphenol B (1,1-bis(4-hydroxyphenyl)adamantane), and bisphenol B (1,1-bis(4-hydroxyphenyl)cyclododecane).

[0014] <Starting material: formaldehyde> Specific examples of formaldehydes, which are one of the starting materials in the novel method for producing a benzoxazine compound of the present invention, include an aqueous formaldehyde solution, 1,3,5-trioxane, and paraformaldehyde.

[0015] <Starting material: amine compound represented by general formula (2)> Specific examples of the amine compound represented by general formula (2), which is one of the starting materials in the method for producing a benzoxazine compound of the present invention, include the following compounds. Specific examples of compounds in which "Y" in general formula (2) is a hydroxy group include methanolamine, 2-aminoethanol, 1-amino-2-propanol, 2-amino-1-methylethanol, 2-amino-2-methylethanol, 3-amino-1-propanol, 4-amino-1-butanol, 2-amino-1-butanol, 4-amino-2-butanol, 5-amino-1-pentanol, 6-amino-1-hexanol, 7-amino-1-heptanol, valinol, 2-aminophenol, 3-aminophenol, 4-aminophenol, and 4-aminobenzyl alcohol. Among these, 2-aminoethanol, 2-amino-1-methylethanol, 2-amino-2-methylethanol, 3-amino-1-propanol, 2-aminophenol, 3-aminophenol, and 4-aminophenol are preferred, 2-aminoethanol, 2-aminophenol, 3-aminophenol, and 4-aminophenol are more preferred, and 2-aminoethanol is particularly preferred. Specific examples of "Y" in general formula (2) being a thiol group include 2-aminoethanethiol, 3-amino-1-propanethiol, 2-amino-1-methylethanethiol, 2-amino-2-methylethanethiol, 5-amino-1-pentanethiol, 6-amino-1-hexanethiol, 2-aminothiophenol, 3-aminothiophenol, 4-aminothiophenol, 4-aminobenzyl mercaptan, etc. Among these, 2-aminoethanethiol, 3-amino-1-propanethiol, 2-aminothiophenol, 3-aminothiophenol, and 4-aminothiophenol are preferred, 2-aminoethanethiol, 2-aminothiophenol, 3-aminothiophenol, and 4-aminothiophenol are more preferred, and 2-aminoethanethiol is particularly preferred.

[0016] <Amount of starting materials used> In the production method of the present invention, the amount of formaldehyde used is preferably in the range of 4.0 to 20.0 mol, more preferably in the range of 4.0 to 16.0 mol, and even more preferably in the range of 4.0 to 12.0 mol, per mol of the bisphenol compound represented by general formula (1). In the production method of the present invention, the amount of the amine compound represented by general formula (2) used is preferably in the range of 2.0 to 10.0 mol, more preferably in the range of 2.0 to 8.0 mol, and even more preferably in the range of 2.0 to 6.0 mol, per 1 mol of the bisphenol compound represented by general formula (1).

[0017] <Catalyst> In the production method of the present invention, no catalyst is particularly required to promote the reaction, but an acid catalyst or a base catalyst can be used as necessary. In this case, usable acid catalysts include concentrated hydrochloric acid, hydrochloric acid gas, trifluoroacetic acid, methanesulfonic acid, p-toluenesulfonic acid, benzoic acid, and mixtures thereof, and usable base catalysts include, but are not limited to, sodium hydroxide, sodium carbonate, triethylamine, triethanolamine, and mixtures thereof. <Solvent> In the production method of the present invention, the reaction is usually carried out in the presence of a solvent. The solvent is not particularly limited as long as it does not inhibit the reaction, but preferred examples include toluene, xylene, ethyl acetate, butyl acetate, chloroform, dichloromethane, tetrahydrofuran, and dioxane. These solvents can be used alone or in combination. The amount of solvent used is not particularly limited as long as it does not interfere with the reaction, but is usually used in the range of 0.5 to 5 times by weight, preferably 1 to 3 times by weight, relative to the bisphenol compound represented by general formula (1). <Reaction temperature> In the production method of the present invention, the reaction temperature is usually in the range of 10 to 150°C. From the viewpoint of the reaction selectivity of the target compound, i.e., the benzoxazine compound represented by general formula (3), the viewpoint of suppressing the production of high-molecular-weight by-products, and the viewpoint of suppressing an increase in viscosity or solidification of the liquid after the reaction, the temperature is preferably in the range of 10 to 80°C, more preferably in the range of 20 to 70°C, even more preferably in the range of 20 to 60°C, and particularly preferably in the range of 20 to 40°C. <Reaction pressure> In the production method of the present invention, the reaction may be carried out under normal pressure, or under increased or reduced pressure. In another embodiment, the method may include a step of removing water derived from the raw materials or water generated during the reaction from the reaction system. The step of removing the generated water from the reaction solution is not particularly limited, and the generated water can be removed by azeotropically distilling the generated water with the solvent system in the reaction solution. The generated water can be removed from the reaction system using, for example, a pressure-equalizing dropping funnel equipped with a stopcock, a Dimroth condenser, a Dean-Stark apparatus, or the like.

[0018] The mixture containing the bisphenol compound represented by general formula (1) and formaldehydes can be obtained by mixing the bisphenol compound represented by general formula (1) with formaldehydes, and the method is not limited thereto, and for example, formaldehydes may be added to a reactor containing the bisphenol compound represented by general formula (1), or vice versa. This mixture may also contain the above-mentioned solvent and catalyst, and the method for mixing them is not limited thereto, but it is preferable to mix the catalyst before mixing the amine compound represented by general formula (2). In the production method of the present invention, the mixture is mixed with an amine compound represented by general formula (2) to carry out the reaction. There are no limitations on the method for mixing the amine compound, but since the production of the benzoxazine compound represented by general formula (3) is an exothermic reaction, it is preferable to mix the amine compound continuously or intermittently so as not to cause a sudden increase in the temperature of the reaction solution, from the viewpoints of reaction selectivity and suppressing the production of high-molecular-weight by-products.

[0019] <After reaction is complete> After the reaction is completed in the production method of the present invention, the benzoxazine compound represented by general formula (3) can be obtained from the reaction mixture by a known method. For example, after the reaction, the target product can be obtained as a residual liquid by distilling off the remaining raw materials and solvent from the reaction mixture. Alternatively, the target product can be obtained by precipitating the residual liquid by adding a poor solvent, or by adding a solvent to the reaction mixture to cause crystallization and filtering the crystals to obtain a powder or granular target product. The benzoxazine compound isolated by the above method can be purified to a high purity by conventional purification means, such as washing with a solvent or water or recrystallization. [Example]

[0020] The present invention will be explained in more detail below with reference to examples. <Analysis method> 1. Reaction solution composition and purity analysis (gel permeation chromatography: GPC) The purity of various benzoxazine compounds synthesized by the production method of the present invention was expressed as the area percentage value of the benzoxazine compound obtained by this analysis. Device: HLC-8320 / Tosoh Corporation Detector: Differential refractometer (RI) [Measurement conditions] Flow rate: 1mL / min Eluent: tetrahydrofuran Temperature: 40℃ Wavelength: 254nm Measurement sample: 1 g of a composition containing a benzoxazine compound was diluted 200 times with tetrahydrofuran.

[0021] Example 1 (Synthesis of Compound p-1 by the Production Method of the Present Invention) [ka] A 1 L four-neck flask equipped with a thermometer, stirrer, condenser, and dropping funnel was charged with 97 g (0.48 mol) of bisphenol F (dinuclear content 90.1 wt%, isomer ratio of which is 18.8 wt% bis(2-hydroxyphenyl)methane, 49.3 wt% 2-hydroxyphenyl-4-hydroxyphenylmethane, and 31.9 wt% bis(4-hydroxyphenyl)methane, polynuclear content 9.9 wt%), 62 g of 94% paraformaldehyde, and 121 g of toluene. No heat generation was observed, and analysis of the mixed solution by high-performance liquid chromatography (HPLC) confirmed that only the raw materials used were present. After purging the reactor with nitrogen, the temperature of the mixed solution was raised to 70°C. While maintaining the temperature, 60 g of 2-aminoethanol was added dropwise to the four-neck flask using the dropping funnel over 2 hours. After the dropwise addition was completed, the mixture was stirred at 70°C for an additional 3 hours. The composition of the reaction solution was analyzed by GPC using the above analytical method, and the proportion of the target compound present in the reaction solution was found to be 51 area %. After the reaction was completed, toluene and water were removed by distillation under reduced pressure at 70°C. The pressure during distillation was gradually reduced to a final pressure of 4.8 kPa. The composition containing the target compound was extracted, cooled and solidified, pulverized, and dried at 60°C and 1.5 kPa to obtain 173 g of the target compound (purity 53%, 47% by area of ​​compounds with a higher molecular weight than the target compound). 1 From the results of H-NMR analysis, it was confirmed that the target benzoxazine compound (p-1) having the above structure was obtained. 1 H-NMR analysis (400 MHz, solvent: CDCl3, reference material: tetramethylsilane) 2.43-2.72(2H,brm),2.71-3.16(4H,m),3.41-4.09(12H,m),4.69-5.01(4H,m),6.49-7.07(6H,m).

[0022] Example 2 (Synthesis of Compound p-2 by the Production Method of the Present Invention) [ka] A 1 L four-neck flask equipped with a thermometer, stirrer, condenser, and dropping funnel was charged with 100 g (0.44 mol) of bisphenol A, 56 g of 94% paraformaldehyde, and 184 g of toluene. No heat generation was observed, and HPLC analysis of the mixed solution confirmed the presence of only the raw materials used. After nitrogen replacement, the temperature of the mixed solution was raised to 70°C. While maintaining the temperature, 53 g of 2-aminoethanol was added dropwise to the four-neck flask using the dropping funnel over 2 hours. After the addition was complete, the mixture was stirred at 70°C for an additional 9.5 hours. The composition of the reaction solution was analyzed by GPC using the above analytical method, and the proportion of the target compound present in the reaction solution was found to be 52 area %. After the reaction was completed, toluene and water were removed by distillation under reduced pressure at 70°C. The pressure during distillation was gradually reduced to 20 kPa. A composition containing the target compound was extracted to obtain 187 g of the target compound (purity: 54%, 46% by area of ​​compounds with a higher molecular weight than the target compound). 1 The results of H-NMR analysis confirmed that the target benzoxazine compound (p-2) having the above chemical structure was obtained. 1 H-NMR analysis (400 MHz, solvent: CDCl3, reference material: tetramethylsilane) 1.14-1.96(6H,m),2.45-2.77(2H,brm),2.78-3.18(4H,m),3.28-4.19(10H,m),4.70-5.14(4H,m),6.56-7.13(6H,m).

[0023] Example 3 (Synthesis of Compound p-3 by the Production Method of the Present Invention-1) [ka] A 500 mL four-neck flask equipped with a thermometer, stirrer, condenser, and dropping funnel was charged with 31 g (0.15 mol) of bisphenol F, 20 g of 94% paraformaldehyde, and 57 g of toluene. No heat generation was observed, and HPLC analysis confirmed that only the raw materials used were present. After nitrogen replacement, the reactor was heated to 60°C and, while maintaining the temperature, 24 g of 2-aminoethanethiol was added to the four-neck flask over 1 hour. After the addition was complete, the mixture was stirred for an additional 2 hours at 60°C. The composition of the reaction solution was analyzed by GPC using the above analytical method. The proportion of the target compound present in the reaction solution was 41 area %. After the reaction was completed, toluene and water were removed by distillation under reduced pressure at 50°C. The pressure during distillation was gradually reduced to a final pressure of 2.4 kPa. A composition containing the target compound was extracted to obtain 59 g of the target compound (purity: 41%, 59 area % of compounds with a higher molecular weight than the target compound). 1 The results of H-NMR analysis confirmed that the target benzoxazine compound (p-3) having the above chemical structure was obtained. 1 H-NMR (400 MHz, solvent: CDCl3, reference material: tetramethylsilane) 1.32-1.95(2H,brm),2.91-3.05(4H,m),3.07-3.22(4H,m),3.64-4.13(10H,m),6.66-7.12(6H,m).

[0024] Example 4 (Synthesis of Compound p-3 by the Production Method of the Present Invention-2) Using a 1 L four-neck flask, 97 g (0.48 mol) of bisphenol F, 62 g of 94% paraformaldehyde, 75 g of 2-aminoethanethiol, and 180 g of toluene, the reaction was carried out in the same manner as in Example 3, except that the temperature before the addition of the amine was set to 50°C and that after the completion of the addition, the mixture was stirred at 50°C for an additional 1 hour. The composition of the reaction solution was analyzed by GPC using the above analytical method, and the proportion of the target compound present in the reaction solution was found to be 65 area %. After the reaction was completed, toluene and water were removed by distillation under reduced pressure at 50°C. The pressure during distillation was gradually reduced to a final pressure of 1.5 kPa. The composition containing the target compound was extracted, cooled and solidified, pulverized, and vacuum dried at 60°C and 1.5 kPa to obtain 208 g of the target compound (purity: 56%, 44% by area of ​​compounds with a higher molecular weight than the target compound).

[0025] Example 5 (Synthesis of Compound p-3 by the Production Method of the Present Invention) Using a 1 L four-neck flask, 97 g (0.48 mol) of bisphenol F, 74 g of 94% paraformaldehyde, 75 g of 2-aminoethanethiol, and 180 g of toluene, the reaction was carried out in the same manner as in Example 3, except that the temperature before the addition of the amine was set to 30°C and that after the completion of the addition, the mixture was stirred at 30°C for a further 3 hours. The composition of the reaction solution was analyzed by GPC using the above analytical method, and the proportion of the target compound present in the reaction solution was found to be 88 area %. After the reaction was completed, the reaction solution was washed with alkaline water using a 3% aqueous sodium hydroxide solution, and then washed with water until the pH of the reaction solution reached 7 or less. Then, toluene and water were removed by distillation under reduced pressure at 30°C. The pressure during distillation was gradually reduced to a final pressure of 2.3 kPa. After removing a certain amount of the solvent, the remaining solvent was further removed under conditions of 90°C and 2.8 kPa. The composition containing the target compound was extracted, cooled to solidify, and then pulverized to obtain 156 g of the target compound (purity: 75%, 25% by area of ​​compounds with a higher molecular weight than the target compound).

[0026] <Reference Example> (Confirmation of the production of intermediates having a hexahydrotriazine structure) A 500 mL four-neck flask equipped with a thermometer, a stirrer, and a breather for checking ventilation was charged with 36 g of 94% paraformaldehyde, 44 g of 2-aminoethanethiol, and 105 g of toluene in that order while nitrogen gas was being passed through. Heat generation was observed from the start of mixing the toluene, and approximately 5 minutes after mixing, the temperature of the mixed solution rose rapidly from 25°C to 40°C, and the inside of the reactor became cloudy with steam. Furthermore, a slight increase in the rate of bubble generation from the breather was observed, indicating an increase in internal pressure. After 1 hour of stirring, the mixed solution 1 As a result of H-NMR analysis, it was confirmed that an intermediate compound having a hexahydrotriazine structure shown below was produced. [ka] 1 H-NMR analysis (400 MHz, solvent: CD3OD, reference material: tetramethylsilane) 2.83(2H,t),3.15(2H,t),4.17(2H,s). From the above, it was confirmed that an amine compound reacts with formaldehyde to produce an intermediate compound having a hexahydrotriazine structure, and that when the raw materials are mixed, the liquid temperature of the mixed solution rises rapidly, smoke is generated inside the reactor, and the internal pressure rises.

[0027] Comparative Example 1 (Synthesis of Compound p-3 Not According to the Production Method of the Present Invention) A 500 mL four-neck flask equipped with a thermometer, a stirrer, and a condenser was charged with 30 g of 94% paraformaldehyde, 36 g of 2-aminoethanethiol, and 88 g of toluene. As in the above-mentioned Reference Example, the temperature of the mixed solution rose rapidly from 25°C to 40°C about 5 minutes after mixing, and the inside of the reactor became cloudy with steam. The atmosphere in the reactor was then replaced with nitrogen, and the mixed solution was heated to 60°C. While maintaining the temperature, 47 g (0.23 mol) of bisphenol F was added. After mixing, the mixture was stirred at 60°C for an additional 3 hours. The composition of the reaction solution was analyzed by GPC using the above analytical method, and the proportion of the target compound present in the reaction solution was found to be 69 area %.

[0028] Example 6 (Synthesis of compound p-5 by the production method of the present invention) [ka] A 1 L four-neck flask equipped with a thermometer, stirrer, condenser, and dropping funnel was charged with 124 g (0.4 mol) of 1,1-bis(4-hydroxyphenyl)-3,3,5-trimethylcyclohexane, 63 g of 92% paraformaldehyde, and 230 g of toluene. No heat generation was observed, and HPLC analysis confirmed that only the raw materials used were present. After nitrogen replacement, the reaction vessel was heated to 30°C, and 49 g of 2-aminoethanol was added dropwise to the four-neck flask using the dropping funnel over 2 hours while maintaining the temperature. After the addition was complete, the mixture was stirred for an additional 4 hours at 30°C. The composition of the reaction solution was analyzed by GPC using the analytical method described above. The proportion of the target compound present in the reaction solution was 79 area %. After the reaction was completed, the reaction mixture was washed with alkaline water using a 3% aqueous sodium hydroxide solution, and then 350 g of toluene was added and washed with water until the pH of the washings reached 7 or less. The toluene and water were then removed by distillation under reduced pressure at 60°C. The pressure during distillation was gradually reduced to a final pressure of 4.8 kPa. After some of the solvent had been removed, the remaining solvent was further removed under conditions of 90°C and 9.8 kPa. 183 g of the target compound (purity: 76%, 24 area % of compounds with a higher molecular weight than the target compound) was obtained. 1 The results of H-NMR analysis confirmed that the target compound (p-5) having the above chemical structure was obtained. 1 H-NMR analysis (400 MHz, solvent: CDCl3, reference material: tetramethylsilane) 0.30-0.40(3H, m), 0.84(1H, m), 0.90-1.00(6H, m), 1.10(1H, m), 1.76-2.02(2H, m), 2.32(1H, m), 2.58(1H, m), 2.81-3.07(4H, m), 3.57-4.05(8H, m), 4.73-4.90(4H, m), 6.50-7.12(6H, m).

[0029] Example 7 (Synthesis of Compound p-6 by the Production Method of the Present Invention) [ka] A reaction was carried out in the same manner as in Example 3 using a 1 L four-neck flask equipped with a thermometer, a stirrer, a condenser, and a dropping funnel, 97 g (0.31 mol) of 1,1'-bis(4-hydroxyphenyl)-3,3,5-trimethylcyclohexane, 48 g of 94% paraformaldehyde, 48 g of 2-aminoethanethiol, and 180 g of toluene, except that the temperature before the addition of the amine was set to 30°C, and after completion of the addition of the amine, the mixture was stirred at 30°C, 40°C, and 50°C for 3 hours each. When 1,1'-bis(4-hydroxyphenyl)-3,3,5-trimethylcyclohexane and 94% paraformaldehyde were mixed, no heat was generated, and HPLC analysis of the mixture confirmed that only the raw materials used were present. The composition of the reaction solution was analyzed by GPC using the above analytical method, and the proportion of the target compound present in the reaction solution was found to be 73 area %. After the reaction was completed, the reaction solution was washed with alkaline water using a 3% aqueous sodium hydroxide solution, and then washed with water until the pH of the reaction solution reached 7 or less. Then, toluene and water were removed by distillation under reduced pressure at 30°C. The pressure during distillation was gradually reduced to a final pressure of 4.2 kPa. After removing a certain amount of the solvent, the remaining solvent was further removed under conditions of 90°C and 20 kPa. The composition containing the target compound was extracted, cooled to solidify, and then pulverized to obtain 188 g of the target compound (purity: 71%, 29 area % of compounds with a higher molecular weight than the target compound). 1 The results of H-NMR analysis confirmed that the target compound (p-6) with the above chemical structure was obtained. 1 H-NMR (400 MHz, solvent: CDCl3, reference material: tetramethylsilane) 0.25-0.44(3H,m)、0.76-1.02(7H,m)、1.11(1H,dd)、1.36(1H,d)、1.75-2.05(2H,m)、2.33(1H,brm)、2.59(1H,brm)、2.77-3.22(8H,m)、3.54-3.79(4H,m)、3.86-4.07(4H,m)、6.51-7.04(6H,m)、9.07-10.3(2H,brm).

Claims

1. A method for producing a benzoxazine compound represented by general formula (3), comprising mixing a mixture containing a bisphenol compound represented by general formula (1) and a formaldehyde compound with an amine compound represented by general formula (2) and reacting them. 【Chemistry 1】 (In the formula, R １ represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and X represents a single bond, an oxygen atom, a sulfur atom, a sulfonyl group, a carbonyl group, or a divalent group represented by general formula (1a) or (1b). 【Chemistry 2】 (In general formulas (1a) and (1b), R ２ and R ３ each independently represents hydrogen, an alkyl group having 1 to 10 carbon atoms, a halogenated alkyl group having 1 to 10 carbon atoms, or an aryl group having 6 to 12 carbon atoms; R ２ and R ３ may be bonded to each other to form a cycloalkylidene group having 5 to 20 carbon atoms as a whole, and Ar １ and Ar ２ each independently represents an aryl group having 6 to 12 carbon atoms, and * indicates the bonding position.) 【Transformation 3】 (In the formula, R ４ represents a divalent group having 1 to 10 carbon atoms, and Y represents a thiol group. 【Chemistry 4】 (In the formula, R １ and X is a group represented by general formula (1), and R ４ and Y represents the same group as in general formula (2).

2. A method for producing a benzoxazine compound represented by general formula (3), comprising mixing a mixture containing a bisphenol compound represented by general formula (1) and a formaldehyde compound with an amine compound represented by general formula (2) and reacting them. 【Transformation 5】 (In the formula, R １ represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and X represents a divalent group represented by general formula (1a). 【Transformation 6】 (In general formula (1a), R ２ and R ３ are both hydrogen or R ２ and R ３ are bonded to each other to form a cycloalkylidene group having 6 to 12 carbon atoms as a whole, and * indicates the bonding position.) 【Transformation 7】 (In the formula, R ４ represents a linear or branched alkylene group having 1 to 4 carbon atoms, and Y represents a hydroxy group. 【Transformation 8】 (In the formula, R １ and X is a group represented by general formula (1), and R ４ and Y represents the same group as in general formula (2).

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