1,3-Dimethyl 2-Corn Product

Abstract

This invention relates to a 1,3-butanediol product, wherein, under specific conditions, in a splitless injection gas chromatography analysis, when the relative retention time of n-dodecane is set to 1.00, the sum of the converted concentrations of n-dodecane among the peaks appearing in the range of relative retention time of 0.80 to 0.99, excluding the peaks of methyl ethyl ketone and the acetal of 1,3-butanediol, is less than 25 ppm.

Description

Technical Field

[0001] This invention relates to a 1,3-butanediol product useful as a raw material for synthetic resins, a raw material for surfactants, a solvent, an antifreeze, a cosmetic ingredient, etc. Prior Technology

[0002] 1,3-Butanediol is a viscous, colorless, transparent, and low-odor liquid with a boiling point of 208°C and excellent chemical stability. Therefore, 1,3-Butanediol can be used as a raw material for various synthetic resins and surfactants. Furthermore, 1,3-Butanediol can be effectively utilized for its excellent hygroscopic properties, low volatility, and low toxicity, making it suitable for use in cosmetics, as a humectant, a high-boiling-point solvent, and an antifreeze. In particular, in recent years, the demand for 1,3-Butanediol has increased significantly in the cosmetics industry due to its excellent properties as a moisturizer, given its low toxicity and irritation.

[0003] Patent document 1 discloses a 1,3-butanediol with less odor, and as a method for obtaining 1,3-butanediol with less odor, it discloses a method for manufacturing 1,3-butanediol by purifying crude 1,3-butanediol through hydrogenation treatment. Previous technical documents Patent documents

[0004] Patent Document 1: Japanese Patent Publication No. 2020-512351 Summary of the Invention

[0005] [The problem the invention aims to solve]

[0006] Here, for example, when 1,3-butanediol is used in the cosmetics field, it is applied directly to the skin. However, the 1,3-butanediol obtained by the method described in Patent Document 1 also has the problem that its skin sensitization cannot be sufficiently reduced. Furthermore, when 1,3-butanediol is used in the cosmetics field, it is sometimes prepared by heating under alkaline conditions. However, in the preparation of mixtures under alkaline conditions, there is also the problem that 1,3-butanediol will cause discoloration.

[0007] In view of the above, the object of the present invention is to provide a 1,3-butanediol product that reduces skin sensitization and is not prone to discoloration under alkaline conditions. [Technical means to solve the problem]

[0008] The inventors conducted intensive research and found that by suppressing the concentration of specific impurities contained in 1,3-butanediol to a certain level, the above-mentioned problems could be solved, thus completing the present invention.

[0009] That is, the present invention is as follows. Furthermore, in this specification, unless otherwise specified, ppm represents mass ppm. [1] A 1,3-butanediol product, wherein, under the following conditions, in a splitless injection gas chromatography analysis, when the relative retention time of n-dodecane is set to 1.00, the sum of the n-dodecane equivalent concentrations of the peaks appearing in the range of relative retention time of 0.80 to 0.99, excluding the peaks of methyl ethyl ketone and the acetal of 1,3-butanediol, is less than 25 ppm. [Conditions for Gas Chromatography Analysis] Analytical column: A column with a stationary phase of (50% cyanopropyl-phenyl)dimethylpolysiloxane (length 30 m × inner diameter 0.25 mm × film thickness 0.25 μm). Heating conditions: Hold at 50℃ for 5 minutes, then increase the temperature from 50℃ to 135℃ at a rate of 10℃ / min, hold at 135℃ for 9 minutes, then increase the temperature from 135℃ to 220℃ at a rate of 15℃ / min, and hold at 220℃ for 12 minutes. Sample introduction temperature: 220℃ Carrier gas: Nitrogen Gas flow rate of the column: 0.5 mL / min Detector and detection temperature: Flame ionization detector (FID), 220℃ Control mode: Constant flow Flow splitting ratio: No flow splitting Inlet venting flush: 60 mL / min Rinse start time: 1 minute Sample injection conditions: 0.6 μL Sample preparation: The sample was prepared by diluting n-dodecane, which is used as an internal standard substance, to 24 ppm with 2-propanol to prepare an internal standard solution, and then mixing 0.5 g of 1,3-butanediol product with 0.1 g of the above internal standard solution. Calculation of the sum of n-dodecane equivalent concentrations: When the relative retention time of n-dodecane detected under the above gas chromatography analysis conditions is set to 1.00, the detection is performed in the range of 0.80 to 0.99 relative retention time, and the total area value (detection peak area value) of the peaks other than the peaks of methyl ethyl ketone and 1,3-butanediol acetals is converted into the sum of n-dodecane equivalent concentrations using the following formula (1). The sum of n-dodecane conversion concentrations (ppm) = n-dodecane concentration (ppm) × detection peak area / n-dodecane area (1) Here, the n-dodecane concentration (ppm) is calculated using the following formula (2). n-Dodecane concentration (ppm) = (mass of n-dodecane in the sample / mass of 1,3-butanediol product in the sample) × 10⁶ (2) [2] A 1,3-butanediol product wherein, under splitless injection gas chromatography analysis under the following conditions, the sum of the n-dodecane equivalent concentrations of the peak of 2-ethylcrotonaldehyde and the peaks of n-butyraldehyde and the acetal of 1,3-butanediol is less than 20 ppm. [Conditions for Gas Chromatography Analysis] Analytical column: A column with a stationary phase of (50% cyanopropyl-phenyl)dimethylpolysiloxane (length 30 m × inner diameter 0.25 mm × film thickness 0.25 μm). Heating conditions: Hold at 50℃ for 5 minutes, then increase the temperature from 50℃ to 135℃ at a rate of 10℃ / min, hold at 135℃ for 9 minutes, then increase the temperature from 135℃ to 220℃ at a rate of 15℃ / min, and hold at 220℃ for 12 minutes. Sample introduction temperature: 220℃ Carrier gas: Nitrogen Gas flow rate of the column: 0.5 mL / min Detector and detection temperature: Flame ionization detector (FID), 220℃ Control mode: Constant flow Flow splitting ratio: No flow splitting Inlet venting flush: 60 mL / min Rinse start time: 1 minute Sample injection conditions: 0.6 μL Sample preparation: The sample was prepared by diluting n-dodecane, which is used as an internal standard substance, to 24 ppm with 2-propanol to prepare an internal standard solution, and then mixing 0.5 g of 1,3-butanediol product with 0.1 g of the above internal standard solution. Calculation of the sum of n-dodecane equivalent concentrations: Using the following formula (1), the total area value (detected peak area value) of the peak of 2-ethylcrotonaldehyde and the peak of n-butyraldehyde and the acetal of 1,3-butanediol detected under the above gas chromatography analysis conditions is converted into the sum of n-dodecane equivalent concentrations. The sum of n-dodecane conversion concentrations (ppm) = n-dodecane concentration (ppm) × detection peak area / n-dodecane area (1) Here, the n-dodecane concentration (ppm) is calculated using the following formula (2). n-Dodecane concentration (ppm) = (mass of n-dodecane in the sample / mass of 1,3-butanediol product in the sample) × 10⁶ (2) [3] The 1,3-butanediol product described in [1] or [2] above, wherein the peak area of ​​1,3-butanediol is greater than 99.5% in gas chromatography analysis under the following conditions. [Conditions for Gas Chromatography Analysis] Analytical column: A column with polyethylene glycol as the stationary phase (length 30 m × inner diameter 0.25 mm × film thickness 0.25 μm). Heating conditions: Increase the temperature from 80℃ to 230℃ at a rate of 5℃ / min, and then maintain the temperature at 230℃ for 10 minutes. Sample introduction temperature: 250℃ Carrier gas: Nitrogen Gas flow rate of the column: 0.5 mL / min Detector and detection temperature: Flame ionization detector (FID), 250℃ Control mode: Constant flow Flow split ratio: 50:1 Sample injection conditions: 1 μL [Effects of the Invention]

[0010] According to the present invention, a 1,3-butanediol product that reduces skin sensitization and is less prone to discoloration under alkaline conditions can be provided. Implementation

[0011] Hereinafter, embodiments of the present invention (hereinafter also referred to as "this embodiment") will be described in detail. The present invention is not limited to the following description and can be implemented with various changes within its scope. Furthermore, in this embodiment, 1,3-butanediol, which is the final product, is referred to as "1,3-butanediol product", and 1,3-butanediol, which is used as a raw material or as an intermediate before becoming the final product, is referred to as "crude 1,3-butanediol".

[0012] [Manufacturing method of 1,3-Butanediol products] (raw material) There are no particular limitations on the crude 1,3-butanediol used as a raw material in the manufacture of the 1,3-butanediol product in this embodiment. Examples include 1,3-butanediol that is sensitizing to the skin or 1,3-butanediol that is discolored under alkaline conditions.

[0013] Regarding crude 1,3-butanediol as a raw material, from the viewpoint of reducing the amount of impurities contained in 1,3-butanediol products, the peak area fraction of 1,3-butanediol in gas chromatography analysis 2 under the following specific conditions is preferably 99.5% or more, more preferably 99.6% or more, and even more preferably 99.7% or more.

[0014] There are no particular limitations on the method for producing crude 1,3-butanediol as a raw material. For example, crude 1,3-butanediol can be produced by known methods (see Japanese Patent Publication No. 3-80139, Japanese Patent Publication No. 7-258129, etc.). Furthermore, it can also be produced by any of the following: by liquid-phase hydrogen reduction of butanol, by hydrolysis of 1,3-epoxybutane, or by fermentation using microorganisms or fungi, or mixtures thereof. Among these, to make the effects of the present invention more significant, it is preferable to use the reaction product obtained by liquid-phase hydrogen reduction of butanol. In the liquid-phase hydrogen reduction method for butyrolaldehyde, low-boiling-point compounds or their condensates, such as acetaldehyde, n-butyraldehyde, crotonaldehyde, and methyl vinyl ketone, which are considered odor-causing substances, are produced as byproducts. These byproducts may also include acetals formed with 1,3-butanediol or with ethanol, and are difficult to remove completely even by distillation. Furthermore, heating steps such as distillation present the following problems: acetaldehyde and n-butyraldehyde may undergo a condensation reaction, resulting in byproducts such as 2-ethylcrotonaldehyde, or acetals formed with 1,3-butanediol. These odor-causing substances include those that are themselves odor sources, or those that have become odorous due to changes over time, heat treatment, or chemical treatment.

[0015] Alternatively, alcohols such as ethanol, salts, and water, which are byproducts, can be removed from the reaction products obtained by the liquid-phase hydrogen reduction of butanol, and the resulting product can be used as crude 1,3-butanediol. There are no limitations on the method for removing these components; methods such as distillation and adsorption can be used.

[0016] Furthermore, the fraction obtained after removing ethanol can be subjected to one or more known purification steps, such as adding an alkali metal compound (e.g., sodium hydroxide, potassium hydroxide, etc.) and then heating it (see Japanese Patent No. 4559625, etc.), and the resulting product can be used as crude 1,3-butanediol. Crude 1,3-butanediol can also be obtained in commercially available form.

[0017] (Hydrogenation process) The method for manufacturing 1,3-butanediol in this embodiment includes a step of hydrogenating crude 1,3-butanediol using a catalyst (hydrogenation step). More specifically, the hydrogenation step is, for example, a process of reducing hydrogen by circulating crude 1,3-butanediol and hydrogen gas through a catalyst layer filled with a catalyst. It is speculated that by using a catalyst to hydrogenate crude 1,3-butanediol, 2-ethylcrotonaldehyde, a substance that causes coloring and skin sensitization under alkaline conditions, and the acetal of n-butyraldehyde and 1,3-butanediol, will be hydrogenated or hydrogenated and decomposed. However, the mechanism of the present invention is not limited to the above.

[0018] The hydrogenation process can be carried out in either the gas phase or the liquid phase, but is preferably carried out in the liquid phase. When carried out in the liquid phase, the reaction temperature can be set at a lower temperature compared to when carried out in the gas phase, thus suppressing the thermal decomposition reaction of 1,3-butanediol. In the hydrogenation process, a Pd / C (Palladium on carbon) catalyst is preferably used. A Pd / C catalyst refers to a catalyst obtained by dispersing and supporting palladium on activated carbon. The loading rate of palladium dispersed and supported on the activated carbon is not particularly limited, but is preferably 0.1% to 30%, more preferably 0.2% to 10%, and even more preferably 0.4% to 1%. Furthermore, the shape of the Pd / C catalyst is not particularly limited, as long as it is in powder, granular, or other similar form.

[0019] The reaction temperature of the hydrogenation step is not particularly limited. When the following heating step is performed, it is preferably 100~150℃, more preferably 110~145℃, and even more preferably 125~135℃. When the following heating step is not performed, it is preferably more than 120℃~150℃, more preferably 125~135℃. When the reaction temperature in the hydrogenation step is below 150°C, the thermal decomposition reaction of 1,3-butanediol will not proceed, and there is a tendency to inhibit the increase of high-boiling-point components. When the temperature is above 100°C (or above 120°C if no heating step is performed), there is a tendency to promote the hydrogenation or hydrogenation decomposition of 2-ethylcrotonaldehyde and n-butyraldehyde with the acetal of 1,3-butanediol.

[0020] The hydrogen pressure in the hydrogenation process is not particularly limited, but is preferably 0.4~1.0 MPa, more preferably 0.5~0.9 MPa, and even more preferably 0.6~0.8 MPa. When the hydrogen pressure in the hydrogenation process is below 1.0 MPa, there is a tendency to reduce equipment costs because it eliminates the need for a sufficiently strong thick-walled device as a high-pressure gas equipment. When the pressure is above 0.4 MPa, there is a tendency to promote the hydrogenation or hydrogenation decomposition of 2-ethylcrotonaldehyde and the acetals of n-butyraldehyde and 1,3-butanediol.

[0021] The method for manufacturing the 1,3-butanediol product in this embodiment is not particularly limited, as long as it includes a step of hydrogenating crude 1,3-butanediol using a catalyst (hydrogenation step). In addition to the hydrogenation step, it may further include one or more of the following steps: a step of heating crude 1,3-butanediol (heating step), and a step of distilling away low-boiling-point components from crude 1,3-butanediol (low-boiling-point distillation step). The order of these steps is not particularly limited, but from the viewpoint of making the effects of the present invention more significant, it is preferred to perform the steps in the order of heating step, hydrogenation step, and low-boiling-point distillation step. The following is a description of each step.

[0022] (Heat treatment step) The heat treatment step in the method for manufacturing 1,3-butanediol products according to this embodiment is a step of heat treatment of crude 1,3-butanediol. By heat treating crude 1,3-butanediol, acetaldehyde and n-butyraldehyde, which are byproducts of 2-ethylcrotonaldehyde, are consumed due to condensation reactions, or n-butyraldehyde, which is a byproduct of the acetalization of n-butyraldehyde and 1,3-butanediol, are consumed. Therefore, in subsequent steps such as distillation accompanied by heating, the amount of 2-ethylcrotonaldehyde and the acetalization of n-butyraldehyde and 1,3-butanediol generated is reduced. Furthermore, by pre-producing 2-ethylcrotonaldehyde or the acetalization of n-butyraldehyde and 1,3-butanediol as byproducts in the heat treatment step, followed by hydrogenation treatment, there is a tendency for these substances to be efficiently decomposed through hydrogenation or hydrogenation decomposition. However, the mechanism of the present invention is not limited to the above.

[0023] The heating time in the heat treatment step is not particularly limited, but it is preferably 20 minutes to 9 hours, more preferably 1 to 6 hours, and even more preferably 1 to 3 hours. When the heating time is more than 20 minutes, the consumption of acetaldehyde and n-butyraldehyde caused by the condensation reaction tends to proceed sufficiently, and when it is less than 9 hours, it tends to suppress the increase in the cost of heat treatment.

[0024] The heating temperature in the heat treatment step is not particularly limited, but is preferably 80~200℃, more preferably 90~120℃, and even more preferably 100~110℃. When the heating temperature is above 80℃, there is a tendency for acetaldehyde and n-butyraldehyde to undergo a condensation reaction. When the temperature is below 200℃, the thermal decomposition reaction of 1,3-butanediol is suppressed, and impurities tend to decrease.

[0025] There are no particular limitations on the heating device used in the heating process. Examples of heating devices include continuous tube type, batch tank type, and continuous tank type. From the point of view of stirring efficiency, batch tank type is preferred.

[0026] (Removal of low-boiling-point distillation steps) The low-boiling-point distillation step in the method for manufacturing the 1,3-butanediol product of this embodiment is, for example, the following step: low-boiling-point components are removed by distillation from the fraction containing a large amount of 1,3-butanediol obtained from the hydrogenation treatment step. Examples of distillation apparatus used in the low-boiling-point distillation step include porous plate columns, bubble cap columns, and packed columns, with a packed column having a theoretical plate count of 7 to 40 being preferred. The distillation column can be a single column or two or more columns. As for distillation conditions, the pressure at the top of the distillation column is preferably 1 to 20 kPa, and the temperature at the bottom of the distillation column is preferably 100 to 160°C, more preferably 110 to 140°C. The specific form of the low-boiling point removal distillation step can be either continuous or batch. For example, as a continuous process, the following method can be used: a fraction containing more 1,3-butanediol is continuously supplied from the top of the distillation column, and while a fraction containing more low-boiling point components is continuously extracted from the top of the column, a fraction containing even more 1,3-butanediol is continuously extracted from the bottom of the column.

[0027] [1,3-Butanediol products] As one embodiment of this invention, a 1,3-butanediol product is provided as follows: under splitless injection gas chromatography analysis under the following conditions, when the relative retention time of n-dodecane is set to 1.00, the sum of the n-dodecane equivalent concentrations of the peaks appearing in the range of relative retention time of 0.80 to 0.99, excluding the peaks of methyl ethyl ketone and the acetal of 1,3-butanediol, is less than 25 ppm. [Conditions for Gas Chromatography Analysis] Analytical column: A column with a stationary phase of (50% cyanopropyl-phenyl)dimethylpolysiloxane (length 30 m × inner diameter 0.25 mm × film thickness 0.25 μm). Heating conditions: Hold at 50℃ for 5 minutes, then increase the temperature from 50℃ to 135℃ at a rate of 10℃ / min, hold at 135℃ for 9 minutes, then increase the temperature from 135℃ to 220℃ at a rate of 15℃ / min, and hold at 220℃ for 12 minutes. Sample introduction temperature: 220℃ Carrier gas: Nitrogen Gas flow rate of the column: 0.5 mL / min Detector and detection temperature: Flame ionization detector (FID), 220℃ Control mode: Constant flow Flow splitting ratio: No flow splitting Inlet venting flush: 60 mL / min Rinse start time: 1 minute Sample injection conditions: 0.6 μL Sample preparation: The sample was prepared by diluting n-dodecane, which is used as an internal standard substance, to 24 ppm with 2-propanol to prepare an internal standard solution, and then mixing 0.5 g of 1,3-butanediol product with 0.1 g of the above internal standard solution. Calculation of the sum of n-dodecane equivalent concentrations: When the relative retention time of n-dodecane detected under the above gas chromatography analysis conditions is set to 1.00, the detection is performed in the range of 0.80 to 0.99 relative retention time, and the total area value (detection peak area value) of the peaks other than the peaks of methyl ethyl ketone and 1,3-butanediol acetals is converted into the sum of n-dodecane equivalent concentrations using the following formula (1). The sum of n-dodecane conversion concentrations (ppm) = n-dodecane concentration (ppm) × detection peak area / n-dodecane area (1) Here, the n-dodecane concentration (ppm) is calculated using the following formula (2). n-Dodecane concentration (ppm) = (mass of n-dodecane in the sample / mass of 1,3-butanediol product in the sample) × 10⁶ (2) Here, as an analytical column, for example, the DB-225 manufactured by Agilent Technologies (30 m in length × 0.25 mm in inner diameter × 0.25 μm in film thickness, stationary phase: (50% cyanopropyl-phenyl)dimethylpolysiloxane) can be used.

[0028] Regarding the 1,3-butanediol product as one of the embodiments of this invention, in order to make the effects of this invention more significant, the sum of the n-dodecane equivalent concentrations of the peaks appearing in the range of relative retention time of 0.80 to 0.99, excluding the peaks of methyl ethyl ketone and the acetal of 1,3-butanediol, is 25 ppm or less, preferably 23 ppm or less, and more preferably 21 ppm or less.

[0029] Furthermore, as one embodiment of this invention, a 1,3-butanediol product is provided in which, under the following conditions, the sum of the dodecane equivalent concentrations of the peak of 2-ethylcrotonaldehyde and the peaks of n-butyraldehyde and the acetal of 1,3-butanediol is less than 20 ppm in a gas chromatography analysis using a splitless injection method. [Conditions for Gas Chromatography Analysis] Analytical column: A column with a stationary phase of (50% cyanopropyl-phenyl)dimethylpolysiloxane (length 30 m × inner diameter 0.25 mm × film thickness 0.25 μm). Heating conditions: Hold at 50℃ for 5 minutes, then increase the temperature from 50℃ to 135℃ at a rate of 10℃ / min, hold at 135℃ for 9 minutes, then increase the temperature from 135℃ to 220℃ at a rate of 15℃ / min, and hold at 220℃ for 12 minutes. Sample introduction temperature: 220℃ Carrier gas: Nitrogen Gas flow rate of the column: 0.5 mL / min Detector and detection temperature: Flame ionization detector (FID), 220℃ Control mode: Constant flow Flow splitting ratio: No flow splitting Inlet venting flush: 60 mL / min Rinse start time: 1 minute Sample injection conditions: 0.6 μL Sample preparation: The sample was prepared by diluting n-dodecane, which is used as an internal standard substance, to 24 ppm with 2-propanol to prepare an internal standard solution, and then mixing 0.5 g of 1,3-butanediol product with 0.1 g of the above internal standard solution. Calculation of the sum of n-dodecane equivalent concentrations: Using the following formula (1), the total area value (detected peak area value) of the peak of 2-ethylcrotonaldehyde and the peak of n-butyraldehyde and the acetal of 1,3-butanediol detected under the above gas chromatography analysis conditions is converted into the sum of n-dodecane equivalent concentrations. The sum of n-dodecane conversion concentrations (ppm) = n-dodecane concentration (ppm) × detection peak area / n-dodecane area (1) Here, the n-dodecane concentration (ppm) is calculated using the following formula (2). n-Dodecane concentration (ppm) = (mass of n-dodecane in the sample / mass of 1,3-butanediol product in the sample) × 10⁶ (2) Here, as an analytical column, for example, the DB-225 manufactured by Agilent Technologies (30 m in length × 0.25 mm in inner diameter × 0.25 μm in film thickness, stationary phase: (50% cyanopropyl-phenyl)dimethylpolysiloxane) can be used.

[0030] Regarding the 1,3-butanediol product as one of the embodiments of this invention, in order to make the effect of this invention more significant, the sum of the dodecane equivalent concentrations of the peak of 2-ethylcrotonaldehyde and the peak of n-butyraldehyde and the acetal of 1,3-butanediol is 20 ppm or less, preferably 16 ppm or less, and more preferably 12 ppm or less.

[0031] Regarding the 1,3-butanediol product of this embodiment, depending on the required product quality, the peak area fraction of 1,3-butanediol in gas chromatography analysis under the following conditions is preferably 99.5% or higher, more preferably 99.7% or higher, further preferably 99.8% or higher, and even more preferably 99.9% or higher. Furthermore, the "peak area fraction" refers to the ratio of the area of ​​a specific peak to the sum of the areas of all peaks appearing in the graph. Also, "all peaks" refers to all peaks that appear when the relative retention time of the 1,3-butanediol peak is set to 1.0 and analysis continues until the relative retention time is stopped at 2.2. By keeping the peak area fraction within the above range, there is a tendency to further reduce odor generation and skin sensitization. [Conditions for Gas Chromatography Analysis] Analytical column: A column with polyethylene glycol as the stationary phase (length 30 m × inner diameter 0.25 mm × film thickness 0.25 μm). Heating conditions: Increase the temperature from 80℃ to 230℃ at a rate of 5℃ / min, and then maintain the temperature at 230℃ for 10 minutes. Sample introduction temperature: 250℃ Carrier gas: Nitrogen Gas flow rate of the column: 0.5 mL / min Detector and detection temperature: Flame ionization detector (FID), 250℃ Control mode: Constant flow Flow split ratio: 50:1 Sample injection conditions: 1 μL Here, as an analytical column, for example, the DB-WAX (a column with polyethylene glycol as the stationary phase; length 30 m × inner diameter 0.25 mm × film thickness 0.25 μm) manufactured by Agilent Technologies can be used.

[0032] [Skin sensitization test] In this embodiment, the 1,3-butanediol product exhibits reduced skin sensitization. Here, skin sensitization refers to an allergic reaction occurring upon skin contact. While laboratory animals are typically used to assess skin sensitization, from an animal protection perspective, the 2015 OECD (Organization for Economic Cooperation and Development) guideline TG442C adopts the Direct Peptide Reactivity Assay (DPRA) as an in vitro chemical analysis test. In this embodiment, skin sensitization is also assessed using the DPRA test. More specifically, skin sensitization is assessed according to the methods described in the following examples.

[0033] [Coloring under alkaline conditions] The 1,3-butanediol product of this embodiment has the advantage of not easily developing color under alkaline conditions. Coloration under alkaline conditions can be evaluated using the method described in the following examples (alkaline coloring test). When evaluating the 1,3-butanediol product of this embodiment using this method, the colorimetric value (b*) of the b* colorimetric system (JIS Z8729) is not particularly limited; for example, based on the average of three measurements, it is preferably 4.0 or less, more preferably 3.8 or less, and even more preferably 3.5 or less. [Example]

[0034] The present invention will be further described in detail below by way of examples, but the present invention is not limited to the following examples. Crude 1,3-butanediol, as the raw material, is obtained by hydrogenating and reducing butanol, followed by de-low-boiling distillation and de-high-boiling distillation (distillation to remove high-boiling components contained in crude 1,3-butanediol). Furthermore, various analyses and evaluations were performed as follows. In gas chromatography analysis 2 under the following conditions, the peak area of ​​crude 1,3-butanediol as the raw material was 99.6%.

[0035] [Gas Chromatography Analysis 1] The 1,3-butanediol products obtained in Examples 1-3 and Comparative Example 1 were subjected to gas chromatography analysis according to the following method 1. (Conditions for Gas Chromatography Analysis 1) Analytical apparatus: Agilent Technologies 7890A gas chromatography system Analytical column: DB-225 manufactured by Agilent Technologies (30 m length × 0.25 mm inner diameter × 0.25 μm film thickness, stationary phase: (50% cyanopropyl-phenyl)dimethylpolysiloxane) Heating conditions: Hold at 50℃ for 5 minutes, then increase the temperature from 50℃ to 135℃ at a rate of 10℃ / min, hold at 135℃ for 9 minutes, then increase the temperature from 135℃ to 220℃ at a rate of 15℃ / min, and hold at 220℃ for 12 minutes. Sample introduction temperature: 220℃ Carrier gas: Nitrogen Gas flow rate of the column: 0.5 mL / min Detector and detection temperature: Flame ionization detector (FID), 220℃ Control mode: Constant flow Flow splitting ratio: No flow splitting Inlet venting flush: 60 mL / min Rinse start time: 1 minute Sample injection conditions: 0.6 μL Sample preparation: An internal standard solution was prepared by diluting n-dodecane (manufactured by GL Science) to 24 ppm with 2-propanol (manufactured by Fujifilm and Koden Pharmaceutical Co., Ltd.). Samples were prepared by mixing 0.5 g of 1,3-butanediol with 0.1 g of the aforementioned internal standard solution. Calculation of the sum of n-dodecane equivalent concentrations: When the relative holding time of n-dodecane detected under the above-mentioned measurement conditions is set to 1.00, the detection is performed when the relative holding time is 0.80 to 0.99. Using the following formula (1), the total area value (detected peak area value) of the peaks other than the peaks of methyl ethyl ketone and the acetal of 1,3-butanediol is converted into the sum of n-dodecane equivalent concentrations, which is taken as the impurity concentration A. Also, using the following formula (1), the total area value (detected peak area value) of the peak of 2-ethylcrotonaldehyde and the peak of n-butyraldehyde and the acetal of 1,3-butanediol is converted into the sum of n-dodecane equivalent concentrations, which is taken as the impurity concentration B. The sum of n-dodecane conversion concentrations (ppm) = n-dodecane concentration (ppm) × detection peak area / n-dodecane area (1) Here, the n-dodecane concentration (ppm) is calculated using the following formula (2). n-Dodecane concentration (ppm) = (mass of n-dodecane in the sample / mass of 1,3-butanediol product in the sample) × 10⁶ (2)

[0036] [Gas Chromatography Analysis 2] The crude 1,3-butanediol used as raw material in Examples 1-3 and Comparative Example 1, and the 1,3-butanediol products obtained in Examples 1-3 and Comparative Example 1, were subjected to gas chromatography analysis according to the following method 2. (Conditions for Gas Chromatography Analysis 2) Analytical apparatus: Agilent Technologies 7890B gas chromatography system Analytical column: DB-WAX (stationary phase polyethylene glycol column; length 30 m × inner diameter 0.25 mm × film thickness 0.25 μm) manufactured by Agilent Technologies. Heating conditions: Increase the temperature from 80℃ to 230℃ at a rate of 5℃ / min, and then maintain the temperature at 230℃ for 10 minutes. Sample introduction temperature: 250℃ Carrier gas: Nitrogen Gas flow rate of the column: 0.5 mL / min Detector and detection temperature: Flame ionization detector (FID), 250℃ Control mode: Constant flow Flow split ratio: 50:1 Sample injection conditions: 1 μL

[0037] [Skin sensitization test] For the 1,3-butanediol products obtained in Examples 1-3 and Comparative Example 1, skin sensitization was assessed according to the following method. (Conditions for skin sensitization testing) 15 mg of cysteine-containing peptide (DPRA) manufactured by Scrum was mixed with 30 mL of 0.05 M phosphate buffer to prepare a 0.05 M phosphate buffer solution containing 0.667 mM of the peptide (hereinafter referred to as the peptide solution). One hour after the preparation of the peptide solution, 750 μL of the peptide solution and 250 μL of acetonitrile were added to each of three HPLC (High Performance Liquid Chromatography) amber sample vials to prepare three reference solutions. Two hours after the preparation of the reference solutions, 750 μL of the peptide solution, 200 μL of acetonitrile, and 50 μL of 1,3-butanediol were added to another HPLC amber sample vial to prepare the test solution (test solution 1). Subsequently, after 4 hours and 6 hours after the preparation of the reference solutions, the test solutions (test solution 2 and test solution 3) were prepared using the same procedure. For each of the three reference solutions and sample solutions (sample solution 1, sample solution 2, and sample solution 3), after 72 ± 2 hours from the time of preparation of each solution, the peptide peak heights of the reference solutions and sample solutions were measured by HPLC, and the average value of the peak heights of the peptides in the reference solutions and sample solutions was calculated three times. Based on the calculated average values ​​of the three times, the peptide reduction rate was calculated using the following formula (3) as the evaluation result. Peptide reduction rate (%) = (average of three peak heights of peptides in the sample solution / average of three peak heights of peptides in the reference solution) × 100 (3) From the point of view of reproducibility, this test was conducted on the same day on the sample solution of the 1,3-butanediol product of Comparative Example 1, which served as the baseline, and the sample solutions of the 1,3-butanediol products of Examples 1 to 3. (Conditions for HPLC analysis in skin sensitization testing) Analysis device: Agilent 1260 InfinityII manufactured by Agilent Technologies Detector: Agilent 1260 Infinity II UV-Vis detector G7114A manufactured by Agilent Technologies Detection wavelength: 220 nm Analytical column: Zorbax SB-C-18 manufactured by Agilent Technologies (particle size 3.5 μm, inner diameter × length = 2.1 mm × 10 mm) Column temperature: 30℃ Measurement time: 20 min Mobile phase: A 0.1% (v / v) trifluoroacetic acid aqueous solution B 0.085% (v / v) trifluoroacetic acid acetonitrile solution gradient: A / B = 90 / 10 ~ 75 / 25 (10 min) A / B = 75 / 25 ~ 10 / 90 (1 min) A / B = 10 / 90 (2 min) A / B = 10 / 90 ~ 90 / 10 (0.5 min) A / B = 90 / 10 (6.5 min) Mobile phase flow rate: 0.35 mL / min Sample injection conditions: 5 μL

[0038] [Alkaline staining test] For the 1,3-butanediol products obtained in Examples 1-3 and Comparative Example 1, the coloring under alkaline conditions was evaluated according to the following method. (Conditions for the alkaline staining test) Add 13 g of water and 2 g of potassium hydroxide to a 100 mL heat-resistant culture medium bottle and mix. Then add 6 g of the 1,3-butanediol product as the target. Next, immerse the heat-resistant culture medium bottle in a water bath and heat at 90°C for 1 hour. After cooling to room temperature, measure the color (b*) of the heat-treated solution using a Nippon Denshoku SE2000 spectrophotometer as a score.

[0039] [Example 1] (Hydrogenation process) Hydrogen reduction (hydrogenation treatment) was carried out in a catalyst layer filled with 10 mL of 0.5% Pd / C catalyst manufactured by NECHEMCAT Corporation. The crude 1,3-butanediol was circulated at an LHSV of 8.0 h⁻¹, and hydrogen gas was circulated at a GHSV of 420 h⁻¹. The hydrogen pressure during the reaction was 0.7 MPa, and the reaction temperature was set at 135°C.

[0040] The obtained 1,3-butanediol product was subjected to gas chromatography analysis. The results showed that, with the relative retention time of n-dodecane set to 1.00, the sum of the converted concentrations of n-dodecane for peaks other than the peaks of methyl ethyl ketone and the acetal of 1,3-butanediol was 21 ppm (impurity concentration A) when the relative retention time was 0.80~0.99. Furthermore, the sum of the converted concentrations of n-dodecane for the peaks of 2-ethylcrotonaldehyde and n-butyraldehyde and the acetal of 1,3-butanediol was 12 ppm (impurity concentration B). For the 1,3-butanediol product, gas chromatography analysis was performed, and the result showed that the peak area of ​​the 1,3-butanediol product was 99.6%. For the 1,3-butanediol product, a skin sensitization test was conducted, and the result showed that the peptide reduction rate was 45 relative to the result of Comparative Example 1, which was set to 100. Furthermore, an alkaline staining test was conducted, and the result showed that the color saturation (b*) was 2.8. The results for these products with 1,3-butanediol are shown in Table 1.

[0041] [Example 2] Except that the reaction temperature of the hydrogenation step was set to 125°C, the process was carried out in the same manner as in Example 1.

[0042] The obtained 1,3-butanediol product was subjected to gas chromatography analysis. The results showed that, with the relative retention time of n-dodecane set to 1.00, and detection performed at relative retention times of 0.80 to 0.99, the sum of the converted concentrations of n-dodecane for all peaks except the peaks of methyl ethyl ketone and the acetal of 1,3-butanediol was 18 ppm (impurity concentration A). Furthermore, the sum of the converted concentrations of n-dodecane for the peaks of 2-ethylcrotonaldehyde and n-butyraldehyde and the acetal of 1,3-butanediol was 10 ppm (impurity concentration B). Gas chromatography analysis was performed on the 1,3-butanediol product, and the result showed that the peak area of ​​the 1,3-butanediol product was 99.6%. For the 1,3-butanediol product, a skin sensitization test was conducted, and the result showed that the peptide reduction rate was 43 relative to the result of Comparative Example 1 (set as 100). Furthermore, an alkaline staining test was conducted, and the result showed that the color saturation (b*) was 3.2.

[0043] [Example 3] (Heat treatment step) In a bath heated to 100°C, crude 1,3-butanediol is circulated with a residence time of 1 hour to carry out heat treatment.

[0044] (Hydrogenation process) Except that the 1,3-butanediol obtained in the above-mentioned heat treatment step was used as the raw material for the hydrogenation step, and the reaction temperature of the hydrogenation step was set to 100°C, the process was carried out in the same manner as in Example 1.

[0045] (Removal of low-boiling-point distillation steps) In a distillation apparatus equipped with a packed column (22 mm inner diameter) filled with Dixon packing material of 3 mm size and a height of 500 mm, 1,3-butanediol obtained in the above-mentioned hydrogenation treatment step was subjected to de-boiling distillation at an oil bath temperature of 126°C and a pressure of 1.6 kPa with a packing height of 415 mm. 10% by weight of the distillate was removed from the top of the distillation apparatus relative to the amount of added liquid, and the 1,3-butanediol product was obtained from the bottom of the distillation apparatus. The obtained 1,3-butanediol product was subjected to gas chromatography analysis. The results showed that, with the relative retention time of n-dodecane set to 1.00, when the relative retention time was between 0.80 and 0.99, the sum of the n-dodecane equivalent concentrations of all peaks except the peaks of methyl ethyl ketone and the acetal of 1,3-butanediol was 0 ppm (impurity concentration A). Furthermore, the sum of the n-dodecane equivalent concentrations of the peaks of 2-ethylcrotonaldehyde and n-butyraldehyde and the acetal of 1,3-butanediol was 0 ppm (impurity concentration B). Gas chromatography analysis was performed on the 1,3-butanediol product, and the result showed that the peak area of ​​the 1,3-butanediol product was 99.7%. For the 1,3-butanediol product, a skin sensitization test was conducted, and the result showed that the relative value of the peptide reduction rate was 22 when the result of Comparative Example 1 was set as 100. Furthermore, an alkaline staining test was conducted, and the result showed that the color saturation (b*) was 0.7.

[0046] [Comparative Example 1] Except that the catalyst in the hydrogen reduction was NiSAT340 manufactured by Clariant (composition: NiO, SiO2, Al2O3, etc.), the process was carried out in the same manner as in Example 1.

[0047] The obtained 1,3-butanediol product was subjected to gas chromatography analysis. The results showed that, with the relative retention time of n-dodecane set to 1.00, the sum of the converted concentrations of n-dodecane for peaks other than the peaks of methyl ethyl ketone and the acetal of 1,3-butanediol was 28 ppm (impurity concentration A) when the relative retention time was 0.80~0.99. Furthermore, the sum of the converted concentrations of n-dodecane for the peaks of 2-ethylcrotonaldehyde and n-butyraldehyde and the acetal of 1,3-butanediol was 27 ppm (impurity concentration B). For the 1,3-butanediol product, gas chromatography analysis was performed, and the result showed that the peak area of ​​the 1,3-butanediol product was 99.6%. For the 1,3-butanediol product, a skin sensitization test was performed, and the obtained peptide reduction rate was set as 100% of the baseline for comparison with the examples. Additionally, an alkaline staining test was conducted, and the result was a color saturation (b*) of 19.6.

[0048] [Table 1] Example 1 Example 2 Example 3 Comparative Example 1 Gas chromatography analysis 1 Impurity concentration A (ppm) twenty one 18 0 28 Impurity concentration B (ppm) 12 10 0 27 Skin sensitization test Relative value of peptide reduction rate 45 43 twenty two 100 alkaline staining test Color saturation (b*) 2.8 3.2 0.7 19.6

[0049] This application is based on Japanese Patent Application No. 2022-083950, filed with the Japan Patent Office on May 23, 2022, the contents of which are incorporated herein by reference. [Industrial Applicability]

[0050] The 1,3-butanediol of this invention is industrially applicable as a raw material for synthetic resins, a raw material for surfactants, a solvent, an antifreeze, a raw material for cosmetics, etc.

Claims

1. A 1,3-butanediol composition product, wherein, under the following conditions, in a splitless injection gas chromatography analysis, with the relative retention time of n-dodecane set to 1.00, the sum of the converted concentrations of n-dodecane among the peaks appearing in the range of relative retention time of 0.80 to 0.99, excluding the peaks of methyl ethyl ketone and the acetal of 1,3-butanediol, exceeds 0 ppm by mass and is less than 25 ppm by mass. [Gas Chromatography Analysis Conditions] Analytical column: A column with a stationary phase of (50% cyanopropyl-phenyl)dimethylpolysiloxane (length 30 m × inner diameter 0.25 mm × film thickness 0.25 μm). Heating conditions: After holding at 50°C for 5 minutes, the temperature is increased from 50°C to 135°C at a rate of 10°C / min, held at 135°C for 9 minutes, then increased from 135°C to 220°C at a rate of 15°C / min, and held at 220°C for 12 minutes. Sample introduction temperature: 220°C. Carrier gas: Nitrogen. Gas flow rate of the column: 0.5 mL / min. Detector and detection temperature: Flame ionization detector (FID), 220°C. Control mode: Constant flow rate. Split ratio: Splitless. Inlet exhaust flushing: 60 mL / min. Flushing start time: 1 minute. Sample injection conditions: 0.6 μL. Sample preparation: The sample is prepared by diluting n-dodecane (used as an internal standard) with 2-propanol to 24 ppm by mass to prepare an internal standard solution. 0.5 g of 1,3-butanediol product is then mixed with 0.1 g of the above internal standard solution to prepare the sample. Calculation of the sum of n-dodecane equivalent concentrations: When the relative retention time of n-dodecane to be detected under the above gas chromatography analysis conditions is set to 1.00, the detection is performed within the range of 0.80 to 0.99 relative retention time, and the sum of the area values ​​of the peaks other than the peaks of methyl ethyl ketone and the acetal of 1,3-butanediol is converted into the sum of n-dodecane equivalent concentrations using the following formula (1): Sum of n-dodecane equivalent concentrations (mass ppm) = n-dodecane concentration (mass ppm) × Detection peak area value / n-dodecane area value (1) Here, the n-dodecane concentration (mass ppm) is the value calculated using the following formula (2): n-dodecane concentration (mass ppm) = (mass of n-dodecane in the sample / mass of 1,3-butanediol product in the sample) × 106 (2), and in the gas chromatography analysis under the following conditions, the peak area of ​​1,3-butanediol is 99.5% or more. [Conditions for Gas Chromatography Analysis] Analytical Column: Polyethylene glycol stationary phase column (length 30 m × inner diameter 0.25 mm × film thickness 0.25 μm) Heating conditions: Increase temperature from 80 °C to 230 °C at 5 °C / min, then hold at 230 °C for 10 minutes Sample introduction temperature: 250 °C Carrier gas: Nitrogen Gas flow rate of the column: 0.Detector and detection temperature: 5 mL / min; Flame ionization detector (FID), 250℃; Control mode: Constant flow rate; Split ratio: 50:1; Sample injection condition: 1 μL.

2. A 1,3-butanediol composition product, wherein, under the following conditions, in a splitless injection gas chromatography analysis, the sum of the n-dodecane equivalent concentrations of the peak of 2-ethylcrotonaldehyde and the peaks of n-butyraldehyde and the acetal of 1,3-butanediol exceeds 0 ppm by mass and is less than 20 ppm by mass. [Gas Chromatography Analysis Conditions] Analytical column: A column with a stationary phase of (50% cyanopropyl-phenyl)dimethylpolysiloxane (length 30 m × inner diameter 0.25 mm × film thickness 0.25 μm). Heating conditions: After holding at 50°C for 5 minutes, the temperature is increased from 50°C to 135°C at 10°C / min, held at 135°C for 9 minutes, and then increased from 135°C to 220°C at 15°C / min, and held at 220°C for 12 minutes. Sample introduction temperature: 220°C. Carrier gas: Nitrogen. Column gas flow rate: 0.5 mL / min detector and detection temperature: Flame ionization detector (FID), 220℃; Control mode: Constant flow rate; Split ratio: Splitless; Inlet exhaust flushing: 60 mL / min; Flushing start time: 1 minute; Sample injection conditions: 0.6 μL Sample Preparation: An internal standard solution was prepared by diluting n-dodecane, which serves as an internal standard, with 2-propanol to 24 ppm by mass. 0.5 g of 1,3-butanediol was then mixed with 0.1 g of the internal standard solution to prepare the sample. Calculation of the Conversion Concentration of n-Dodecane: Using the following formula (1), the sum of the peak areas (detected peak areas) of the 2-ethylcrotonaldehyde peak and the peaks of the acetals of n-butyraldehyde and 1,3-butanediol detected under the above gas chromatography analysis conditions was converted to the conversion concentration of n-dodecane. Conversion Concentration of n-Dodecane (mass ppm) = n-Dodecane Concentration (mass ppm) × Detected Peak Area / n-Dodecane Area (1) Here, the n-dodecane concentration (mass ppm) is calculated using the following formula (2): n-Dodecane Concentration (mass ppm) = (Mass of n-dodecane in the sample / Mass of 1,3-butanediol in the sample) × 10⁶ (2) And in the gas chromatography analysis under the following conditions, the peak area of ​​1,3-butanediol is above 99.5% [Gas chromatography analysis conditions] Analytical column: column with polyethylene glycol as stationary phase (length 30 m × inner diameter 0.25 mm × film thickness 0.25 μm) Heating conditions: heating from 80°C to 230°C at 5°C / min and holding at 230°C for 10 minutes Sample introduction temperature: 250°C Carrier gas: nitrogen Gas flow rate of column: 0.5 mL / min Detector and detection temperature: flame ionization detector (FID), 250°C Control mode: constant flow rate Split ratio: 50:1 Sample injection conditions: 1 μL.