JP3915253B2 - Method for producing ω-halogenoalkylstyrene derivative - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing a ω-halogenoalkylstyrene derivative, which is an organic intermediate important for producing a functional material such as a pharmaceutical or agrochemical. Specifically, the present invention relates to a method for producing an ω-halogenoalkylstyrene derivative capable of efficiently removing a by-product polymer.
[0002]
[Prior art]
Conventionally, ω-halogenoalkylstyrene derivatives have been used as raw materials for various functional agents. For example, pharmaceutical (for example, cholesterol reducing agent), agrochemical intermediate raw material, ion exchange resin, ion exchange membrane, ion exchange fiber, solid phase synthesis carrier, combinatorial synthesis carrier, chromatography (column filler) carrier, chelate Examples thereof include a resin, an immobilization carrier, a functional film, an adsorbent, a high-performance polymer, a photosensitive material, a conductive material, and a silane coupling agent.
[0003]
Many proposals have been made regarding methods for producing halogenoalkylstyrene derivatives. For example, in JP-A-4-349994, 1, (ω-1) -dihalogenoalkane is allowed to act on a Grignard reagent (vinylbenzylmagnesium halide) of chloromethylstyrene (CMS) to synthesize an ω-halogenoalkylstyrene derivative. In addition, J. of Polymer Science and Polymer Chemistry Edition, Vol. 20, 1982, P3015 discloses a method for synthesizing 3-bromopropylstyrene using chlorostyrene as a raw material.
[0004]
However, in this production method, the target ω-halogenoalkylstyrene derivative is obtained, but the target polymer, ω-halogenoalkylstyrene polymer, is produced as a by-product to some extent. As a method for removing the polymer by-produced by the reaction, a method of purification by column chromatography or vacuum distillation is generally known. These methods also remove the by-product polymer to obtain a halogenoalkylstyrene derivative with high purity. Obtainable. For example, in column chromatography purification, the polymer component is adsorbed, so that the polymer is not contained in the eluted solution. In the case of vacuum distillation purification, since the polymer component usually has a boiling point higher than that of the monomer, it can be easily removed to the end as the residue.
[0005]
However, column purification requires a great deal of cost (solvent, packing material, time) when manufacturing in large quantities. On the other hand, vacuum distillation is possible when a small amount of halogenoalkylstyrene derivative is obtained. However, halogenoalkyl styrene has the following properties: (1) the boiling point of the styrene derivative is relatively high, (2) the thermal polymerization of the styrene derivative is high, and (3) the thermal stability of the terminal functional group. The (batch type) vacuum distillation method is not preferred for obtaining a large amount of the target product due to the properties such as
[0006]
[Problems to be solved by the invention]
On the other hand, the thin film distillation method is suitable for treating a polymerizable monomer such as a halogenoalkylstyrene derivative with a short residence time.
However, even in the thin film distillation method, in the process of separating the styrene derivative and its polymer, depending on the distillation conditions, since the styrene derivative is not included in the bottom component (pot residue), it loses the fluidity of the bottom component and is solidified. The stirring of the wiper cannot be continued. Further, even in the centrifugal thin film distillation method, it becomes difficult to form a liquid film on the centrifuge with the concentrated polymer, the separation performance is lowered, and the distillation becomes difficult.
[0007]
As described above, it has been difficult to efficiently produce a high-purity ω-halogenoalkylstyrene derivative by a known method.
The present invention has been made in view of the above circumstances, and an object of the present invention is to efficiently remove high-boiling components such as a by-product polymer in a method for producing ω-halogenoalkylstyrene, and to produce an ω-halogenoalkylstyrene derivative. It is to provide a method for efficiently and inexpensively manufacturing a product.
[0008]
[Means for Solving the Problems]
As a result of intensive studies to achieve the above object, the present inventors have conducted thin-film distillation purification in the presence of a chemically stable high-boiling solvent in the method for producing an ω-halogenoalkylstyrene derivative. The inventors have found that the ω-halogenoalkylstyrene derivative can be recovered with high purity while maintaining the fluidity of the residual component of the kettle, and have reached the present invention.
That is, the gist of the present invention is the following general formula (1) containing a high boiling component.
[0009]
[Chemical 2]
[0010]
(Wherein n represents an integer of 3 to 8, X represents a halogen atom, R represents a hydrogen atom, an alkyl group, or a halogen atom, respectively), a boiling point of 300 ° C. or higher. , A method for producing an ω-halogenoalkylstyrene derivative, characterized in that thin-film distillation is performed in the presence of a high-boiling solvent having a viscosity of 1000 cp or less at 25 ° C.
[0011]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, the present invention will be described in detail.
What is an ω-halogenoalkylstyrene derivative in the present invention?
[0012]
[Chemical 3]
[0013]
It is a linear alkylstyrene derivative having a halogen at the terminal represented by the general formula (1). In the formula, the number n of methylene chains is an integer of 3 to 8. Examples of the compound represented by the formula (1) include bromopropyl styrene, iodopropyl styrene, chlorobutyl styrene, bromobutyl styrene, chloropentyl styrene, iodopentyl styrene, chlorohexyl styrene, bromohexyl styrene, bromooctyl styrene, and the like. Is mentioned.
[0014]
These styrene derivatives can be produced by the method disclosed in JP-A-4-349994.
For example, a method in which a polyalkylene dihalide is reacted with a chloromethylated base monomer (for example, chloromethylstyrene) by a Grignard method, or a polyalkylene dihalide is reacted with a chlorinated base monomer (chlorostyrene) by a Grignard method Method.
The reaction product obtained by these methods contains a considerable amount of a high boiling component such as a target polymer, that is, a ω-halogenoalkylstyrene polymer, together with the target ω-halogenoalkylstyrene derivative.
[0015]
In the present invention, a reaction mixture containing a halogenoalkylstyrene derivative, which is a target product obtained by the above-described method, and a high-boiling component such as a polymer, which is a byproduct, is obtained by subjecting a solution and polymer containing the halogenoalkylstyrene derivative to thin film distillation. The process of separating high boiling components such as these is essential. In the thin film distillation, a high boiling point solvent is added as a coating agent for the evaporation surface of the thin film device so that a liquid film can always be formed on the evaporation surface of the thin film device.
[0016]
In order to achieve this object, the high boiling point solvent preferably satisfies the following conditions.
(1) The boiling point of the high-boiling solvent is high (at least the boiling point is higher than the target styrene derivative), (2) The heat medium decomposes at the thin-film distillation temperature and conditions (retention time), and the low-boiling compound (3) Low viscosity even at room temperature, (4) Good compatibility between polymer component and heat medium, (5) High-boiling solvent is inexpensive, and (6) Incineration disposal Is that the constituent element of the high-boiling point solvent is composed of C, H, and O (which may contain a small amount of halogen depending on the degree).
[0017]
In (1), the boiling point of the high-boiling solvent is desirably much higher than that in the halogenoalkylstyrene derivative, and is usually 300 ° C. or higher, in order to keep the high-boiling solvent mixed in the halogenoalkylstyrene derivative low.
In (2), the high boiling point medium should not be decomposed at the thin film distillation temperature (about 70 ° C. to 180 ° C. depending on the degree of vacuum) when removing the high boiling point component.
(3) When handling a high-boiling point medium, the lower the viscosity, the better the workability. When mixed with a concentrated liquid containing a halogenoalkylstyrene derivative, the viscosity of the high-boiling point solvent is reduced. Is preferably as low as possible. In order to lower the viscosity of the kettle residue after thin-film distillation of the high boiling point component, it is preferable that the viscosity of the high boiling point solvent is low. For example, the viscosity at 25 ° C. is desirably 1000 cp or less.
[0018]
(4) must be highly compatible with the polymer component so that the polymer component does not precipitate / precipitate when a concentrated solution containing a high boiling point solvent and a halogenoalkylstyrene derivative is mixed. For example, glycerin ester, polyglycol, cellulose, polyvinyl alcohol, and the like have high polarity, and when these are added, precipitates are deposited.
(5) is important for producing a halogenoalkylstyrene derivative at low cost.
In (6), the residue after thin film distillation of the high boiling point component is disposed of by combustion. Considering incineration, it is desirable not to contain metal atoms in addition to phosphorus atoms, sulfur, nitrogen atoms, and silicon atoms. Further, the halogenoalkylstyrene derivative contains a halogen atom, but the high boiling point solvent preferably does not contain a halogen atom. Therefore, it is desirable that the constituent elements of the high-boiling solvent are carbon atoms, hydrogen atoms, and, if necessary, oxygen atoms.
[0019]
In order to satisfy the above conditions, SK oil used as a heat medium for the reactor (for example, manufactured by Soken Chemical Co., Ltd., trade name: Neo SK oil 1400 (boiling point 391 ° C., viscosity 15 cp / 40 ° C.), SK oil L-400 (boiling point 440 ° C., viscosity 159 cp / 0 ° C.), dioctyl phthalate (boiling point 386 ° C.) added as plastic plasticizer, diisononyl phthalate (viscosity 55 cp / 25 ° C.), 2-ethylhexyl phthalate Phthalic acid diesters such as diisodecyl phthalate (boiling point 420 ° C.), diisotridecyl phthalate (boiling point 250 ° C./2 mmHg), butylbenzyl phthalate (boiling point 370 ° C.), tris-2-ethylhexyl trimellitic acid (boiling point 430 ° C.) Trimellitic acid plasticizers such as tricresyl phosphate (boiling point 420 ° C., viscosity 57 p / 25 ° C), tris-2-ethylhexyl phosphate (boiling point 220-250 ° C / 5 mmHg), trichloroethyl phosphate (boiling point 210-220 ° C / 20 mmHg, viscosity 35 cp / 25 ° C)), triphenyl phosphate (boiling point) 260 ° C./20 mmHg) and the like, di-2-ethylhexyl adipate, dioctyl adipate (boiling point 335 ° C.), di-2-ethylhexyl sebacate, dioctyl sebacate (boiling point 377 ° C.), di-maleate Fatty acid dibasic acid esters such as 2-ethylhexyl (boiling point 195-207 ° C./5 mmHg, viscosity 17 cp / 23 ° C.), oxyacid esters such as butyl acetylricinoleate, chlorinated paraffin, chlorinated biphenyl, dinonylnaphthalene Etc. Of these, dialkyl phthalate plasticizers are preferred. Examples thereof include diisodecyl phthalate (DIDP), diisotridecyl phthalate (DTDP), and tricresyl phosphate.
[0020]
The amount of the high-boiling solvent added varies depending on the molecular weight of the by-produced polymer, but is preferably 50% by weight to 1000% by weight based on the weight of the polymer contained. Furthermore, 100 to 400 weight% is preferable. When the amount of the high boiling point solvent is too small, stirring of the thin film apparatus becomes difficult, or the tube of the bottoms (residue) is blocked. On the other hand, when the amount of the heat medium is too large, not only the production efficiency of the halogenoalkylstyrene derivative is lowered, but also the recovery rate is lowered.
[0021]
In the present invention, the high boiling point solvent only needs to be present when the oligomer / polymer component is removed, and the addition point is not particularly limited. For example, when the high boiling point component is removed first, it is necessary to add a high boiling point solvent at the start of the thin film distillation. Conversely, when removing light boiling components (solvents, excess carbon increasing agents, etc.) first and removing high boiling components in the final stage of thin film distillation, they may be added from the beginning. However, what is necessary is just to add in the case of removal of a high boiling component.
In the thin film distillation in the present invention, the residence time is generally several seconds to 5 minutes, preferably about several seconds to 2 minutes. The degree of vacuum is about 0.1 to 10 mm / Hg, preferably about 0.1 to 2 mm / Hg, and the temperature is about 80 to 200 ° C. .
[0022]
【Example】
EXAMPLES Specific examples of the present invention will be described below in more detail with reference to examples. However, the present invention is not limited to these examples unless it exceeds the gist.
[0023]
Example 1
Production of 4- (4-bromobutyl) styrene Nitrogen gas inlet tube, Jimloh cooling tube, isobaric dropping funnel with branch tube, mercury thermometer, thermocouple for thermometer, metal magnesium in jacketed 3L reactor equipped with stirring blade 140.9 g (5.40 gram atoms, 1.45 equivalents / ClSt) was added, and the atmosphere was sufficiently replaced with dry nitrogen gas, and the jacket temperature was set to 20 ° C. On the other hand, 865 g (3.0 equivalents / ClSt) of dry degassed THF, 921 g (2.5 equivalents / ClSt) of dry degassed toluene, and dry degassed chlorostyrene (ClSt) (4-chlorostyrene) were added to an equal pressure dropping funnel with a branch pipe. Only 554 g (4.0 mol) of a solution was prepared, initially 40 ml of dry THF was added, 30 ml of ClSt in THF-TL was added dropwise, and 0.3 ml of 1,2-dibromoethane was added dropwise, and the solution foamed. At the same time as ethylene was generated, the temperature of the solution suddenly increased and temporarily reached 38 ° C. After a few minutes, the solution became light grayish green, and after 10 minutes, it became a dark green solution. The solution was continuously added dropwise over 3 hours so that the solution became 25 to 29 ° C. After completion of the addition, the jacket temperature was adjusted so that the internal temperature became 27 ° C., and the Grignard reagent was added dropwise. After stirring for 3 hours, the raw material chlorostyrene decreased to 0.1% or less (HPLC analysis), and the prepared ClSt Grignard reagent was cooled to 10 ° C. and used for the Grignard reaction in the second step.
[0024]
For the Grignard reaction, a jacketed 5 L reactor equipped with a nitrogen gas introduction tube, a Jimroh cooling tube, a mercury thermometer, a thermocouple for a temperature recorder, a stirring blade, and a Grignard solution dropping tube was replaced with dry nitrogen. Into this, 115 g of THF (0.4 eq / ClSt) and 13.3 g of catalyst Li ₂ CuCl ₄ (0.06 mol, 1.5 mol% / ClSt) were added and dissolved to obtain a deep orange transparent solution. Further, 3454 g (16.0 mol, 4.0 equivalents / ClSt) of 1,4-dibromobutane was added, and the mixture was cooled to 10 ° C. Into this, the Grignard reagent prepared on the left was dropped slowly over 3 hours so that the internal temperature did not exceed 10 ° C. When about 20 ml of Grignard reagent was dropped, the solution became a deep orange to light yellow solution, and further a colorless and transparent solution. When dripping was further continued, the green to dark (black) green transparent solution was obtained. After completion of the dropwise addition, the reaction was completed by stirring at 15 ° C. for 1 hour. After aging, 20 ml of methanol was dropped into the solution to complete the reaction. The yield of the desired 4- (4-bromobutyl) styrene was 84%. The other components were 0.2% 4,4-divinylbiphenyl, 6.8% 1,4-divinylphenylbutane, 2% styrene, and about 4% polymer (polybromobutylstyrene).
Demineralized water was added and the mixture was allowed to stand for liquid separation, and the aqueous phase was removed. Under reduced pressure, the solvent used in the reaction, THF, toluene, and styrene partially produced in the reaction were removed. This concentrate was further purified by thin film distillation.
[0025]
This concentrated liquid was supplied at 300 g / hr to wiperene (manufactured by Shinko Pantech, 2-03 type heat transfer surface area: 0.034 m ² ), and 1,4-dibromobutane was removed at 75 ° C./5 to 10 mmHg. In the first thin film production, 4- (4-bromobutyl) styrene was concentrated to 52%. Further, this concentrated solution was supplied at 400 g / hr, and 1,4-dibromobutane was removed at 70 ° C./1 to 2 mmHg. 4- (4-Bromobutyl) styrene was concentrated to 82%. In the third thin film production, 300 g / hr was supplied at 67 ° C./0.5 to 0.8 mmHg and concentrated to 91% to obtain 890 g of 4- (4-bromobutyl) styrene. The solution became a viscous solution.
[0026]
To this concentrated solution, 105 g of diisotridecyl phthalate (C13 diester) (manufactured by Kao; Vinicizer 20) was added and dissolved at room temperature. The concentrated solution was supplied at 200 g / hr under distillation conditions of 160 ° C./0.5 mmHg to produce a thin film. As distillate components, 760 g of 4- (4-bromobutyl) styrene, 10.5 g of divinylphenylbutane, 23 g of 1,4-dibromobutane, and 0.7 g of diisotridecyl phthalate were obtained. The bottom component was 101 g of diisotridecyl phthalate, 0.6 g of 4- (4-bromobutyl) styrene, 21.1 g of divinylphenylbutane, and 65 g of 4- (4-bromobutyl) styrene polymer.
The analysis was performed as follows.
[0027]
HPLC analysis; ODS column: Inertsil ODS-2, eluent: 80% MeOH aqueous solution, flow rate: 2.00 ml / min, detector: UV254 nm, column temperature: 25 ° C.
[0028]
The plasticizer DTDP was performed under the following conditions. Inertsil ODS-2, eluent: 100% MeOH aqueous solution, flow rate: 1.00 ml / min, detector: UV254 nm, column temperature: 25 ° C.
[0029]
GC analysis: GC column HP-1 (Hewlett Packard) or DB-1 (J & W) (ID 0.25 mm × 30 m), 50 ° C. (3 min hold) → 10 ° C./min→280° C. (3 min hold), detector: FID, Flow rate 2.00ml / min, split ratio; 1/50, constant flow program
The plasticizer DTDP was performed under the following conditions. DB-1 (J & W) (ID 0.25 mm × 30 m), 300 (3 min hold) → 5 ° C./min→350° C. (10 min hold), detector: FID, flow rate 2.00 ml / min, split ratio: 1/50, Constant flow program [0031]
Example 2
Production of 4- (3-chloropropyl) styrene In Example 1, except that 1260 g (2.0 equivalents / ClSt) of 1-bromo-3-chloropropane was used instead of 1,4-dibromobutane as the carbon-increasing agent. Reacted in the same way. The yield of the desired 4- (3-bromopropyl) styrene was 65%. Demineralized water was added and the mixture was allowed to stand for liquid separation, and the aqueous phase was removed. Under reduced pressure, the solvent used in the reaction, THF, toluene, and styrene partially produced in the reaction were removed. This concentrate was further purified by thin film distillation.
[0032]
This concentrated solution was supplied to a thin film distiller at 400 g / hr, and 1-bromo-3-chloropropane was removed at 50 ° C./5 mmHg. The conditions for the second thin film distillation were 50 ° C./2 mmHg at a supply rate of 350 g / hr, and the third thin film distillation conditions were supplied at 45 ° C./0.8 mm Hg at 300 g / hr and concentrated to 74% to obtain 620 g. It was. The solution became a viscous solution.
[0033]
To this concentrated solution, 250 g of diisotridecyl phthalate (C13 diester) (Kao Vinicizer 20) was added at room temperature and dissolved. The concentrated solution was supplied at 200 g / hr under distillation conditions of 140 ° C./0.5 mmHg to produce a thin film. As distillate components, 440 g of 4- (3-chloropropyl) styrene, 8 g of 1-bromo-3-chloropropane, and 0.4 g of diisotridecyl phthalate were obtained. The bottom component was 241 g of diisotridecyl phthalate, 0.6 g of 4- (3-chloropropyl) styrene, 1.1 g of divinylbiphenyl, and 142 g of 4- (3-chloropropyl) styrene polymer.
[0034]
Example 3
Production of 4- (6-bromohexyl) styrene In Example 1, except that 4879 g of 1,6-dibromohexane (5 equivalents / ClSt) was used instead of 1,4-dibromobutane as the carbon increasing agent. Reaction was performed. In order to remove 1,6-dibromohexane, thin film distillation was performed at 90 ° C./5 mmHg for the first time, 85 ° C./2 mmHg for the second time, and 75 ° C./0.7 mmHg for the third time. As a high boiling component, 170 g of diisotridecyl phthalate (C13 diester) (manufactured by Kao Vinicizer 20 / Kyowa Hakko) is added at room temperature, and a concentrated solution is supplied at 200 g / hr under distillation conditions of 180 ° C./0.5 mmHg. Purified. As distillate components, 854 g of 4- (6-bromohexyl) styrene and 0.4 g of diisotridecyl phthalate (DTDP) were obtained.
[0035]
Example 4
A thin film distillation for removing a high boiling point component (polymer) was examined using a concentrated liquid of the following can components. The composition of the concentrate is 74% 4- (4-bromobutyl) styrene, 7% divinylphenylbutane, and 19% polymer.
350 g of a high-boiling solvent (neo SK-oil 1400, manufactured by Soken Chemical) was added to 800 g of the concentrated liquid of this can component, and thin film distillation was examined at the temperatures shown in Tables 1 to 2. The degree of vacuum was examined within the range of 0.8 to 1.0 mmHg.
Table 1 shows the results of studies on thin-film distillation using DTDP, Table 2 as DIDP, and Table 3 as NeoSK-oil 1400 as high-boiling solvents. In the table, the recovery rate of the light boiling component (distilled component side) product (4- (4-bromobutyl) styrene) and the product to the bottom component (high boiling component side) (4- (4-bromobutyl) The mixing ratio of styrene was shown.
[0036]
Comparative Example 1
The thin film distillation conditions were examined using the concentrate of the bottom component used in Example 4. The degree of vacuum was 0.8 mmHg to 1.0 mmHg.
When the thin film distillation temperature was set to 140 ° C. and the concentrated liquid was supplied without using a high boiling point solvent, 30 minutes later, an abnormal sound was generated inside the thin film distillation apparatus (at first, a rattling sound, gradually sounding angry). Begins to occur and a polymer precipitates at the bottom. When further continued, the polymer began to adhere to some of the cooling pipes, and the product began to mix into the spilled components. When the distillation was continued for another hour, the polymer precipitated at the lower part of the evaporation surface, and the wiper could not be stirred, so that the thin film distillation was stopped.
[0037]
[Table 1]
[0038]
[Table 2]
[0039]
[Table 3]
[0040]
【The invention's effect】
According to the method for producing an ω-halogenoalkylstyrene derivative of the method of the present invention, the by-product polymer can be efficiently removed, and the target ω-halogenoalkylstyrene derivative can be produced at a low cost and in a high yield. .

Claims (7)

The following general formula (1) containing a high boiling component
(Wherein n represents an integer of 3 to 8, X represents a halogen atom, R represents a hydrogen atom, an alkyl group, or a halogen atom, respectively), a boiling point of 300 ° C. or higher. A method for producing an ω-halogenoalkylstyrene derivative, comprising thin-film distillation in the presence of a high-boiling solvent having a viscosity of 1000 cp or less at 25 ° C. The method for producing an ω-halogenoalkylstyrene derivative according to claim 1, wherein the high boiling point solvent contains carbon atoms, hydrogen atoms and oxygen atoms as constituent elements. The method for producing an ω-halogenoalkylstyrene derivative according to claim 1 or 2 , wherein the amount of the high-boiling solvent added is 50 to 1000% by weight based on the polymer contained. The method for producing an ω-halogenoalkylstyrene derivative according to any one of claims 1 to 3 , wherein the high boiling point solvent is diisotridecyl phthalate (DTDP). The method for producing an ω-halogenoalkylstyrene derivative according to any one of claims 1 to 3 , wherein the high-boiling solvent is diisodecyl phthalate (DIDP). The method for producing an ω-halogenoalkylstyrene derivative according to any one of claims 1 to 3 , wherein the high-boiling solvent is a dibenzyltoluene derivative. The method for producing an ω-halogenoalkylstyrene derivative according to any one of claims 1 to 6, wherein the high boiling point solvent is added at the start of the thin film distillation.