WO2022255436A1 - 製品1,3-ブチレングリコール - Google Patents
製品1,3-ブチレングリコール Download PDFInfo
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- WO2022255436A1 WO2022255436A1 PCT/JP2022/022426 JP2022022426W WO2022255436A1 WO 2022255436 A1 WO2022255436 A1 WO 2022255436A1 JP 2022022426 W JP2022022426 W JP 2022022426W WO 2022255436 A1 WO2022255436 A1 WO 2022255436A1
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- WIPO (PCT)
- Prior art keywords
- butylene glycol
- product
- relative retention
- retention time
- dinitrophenylhydrazine
- Prior art date
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- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 title claims abstract description 220
- 235000019437 butane-1,3-diol Nutrition 0.000 title claims abstract description 111
- 229940058015 1,3-butylene glycol Drugs 0.000 title claims abstract description 110
- 230000014759 maintenance of location Effects 0.000 claims abstract description 34
- 238000004128 high performance liquid chromatography Methods 0.000 claims abstract description 29
- HORQAOAYAYGIBM-UHFFFAOYSA-N 2,4-dinitrophenylhydrazine Chemical compound NNC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O HORQAOAYAYGIBM-UHFFFAOYSA-N 0.000 claims abstract description 25
- 150000001728 carbonyl compounds Chemical class 0.000 claims abstract description 15
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- WVVOBOZHTQJXPB-UHFFFAOYSA-N N-anilino-N-nitronitramide Chemical class [N+](=O)([O-])N(NC1=CC=CC=C1)[N+](=O)[O-] WVVOBOZHTQJXPB-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000002835 absorbance Methods 0.000 claims abstract description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 33
- 239000000243 solution Substances 0.000 claims description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- 238000005259 measurement Methods 0.000 claims description 18
- 238000004458 analytical method Methods 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 239000012535 impurity Substances 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 238000001514 detection method Methods 0.000 claims description 7
- 238000002347 injection Methods 0.000 claims description 7
- 239000007924 injection Substances 0.000 claims description 7
- 239000002245 particle Substances 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical class O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 239000012153 distilled water Substances 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 239000011148 porous material Substances 0.000 claims description 4
- 230000005526 G1 to G0 transition Effects 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- 241000206601 Carnobacterium mobile Species 0.000 claims description 2
- 238000004821 distillation Methods 0.000 description 34
- 239000000047 product Substances 0.000 description 32
- 239000000523 sample Substances 0.000 description 30
- 238000010438 heat treatment Methods 0.000 description 26
- 238000000034 method Methods 0.000 description 26
- 206010070835 Skin sensitisation Diseases 0.000 description 18
- 239000010410 layer Substances 0.000 description 18
- 231100000370 skin sensitisation Toxicity 0.000 description 18
- 108090000765 processed proteins & peptides Proteins 0.000 description 17
- 238000012360 testing method Methods 0.000 description 17
- 238000000605 extraction Methods 0.000 description 16
- 238000009835 boiling Methods 0.000 description 14
- 239000003960 organic solvent Substances 0.000 description 13
- 239000012071 phase Substances 0.000 description 13
- 239000002994 raw material Substances 0.000 description 12
- 230000009467 reduction Effects 0.000 description 12
- 230000018044 dehydration Effects 0.000 description 11
- 238000006297 dehydration reaction Methods 0.000 description 11
- 238000004817 gas chromatography Methods 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 11
- 239000000126 substance Substances 0.000 description 10
- 238000005516 engineering process Methods 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 8
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 8
- FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 description 8
- 238000011156 evaluation Methods 0.000 description 8
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 8
- -1 1,3-butylene Chemical group 0.000 description 7
- 239000012488 sample solution Substances 0.000 description 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- QQZOPKMRPOGIEB-UHFFFAOYSA-N 2-Oxohexane Chemical compound CCCCC(C)=O QQZOPKMRPOGIEB-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 239000002537 cosmetic Substances 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000012790 confirmation Methods 0.000 description 4
- MLUCVPSAIODCQM-NSCUHMNNSA-N crotonaldehyde Chemical compound C\C=C\C=O MLUCVPSAIODCQM-NSCUHMNNSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 238000005979 thermal decomposition reaction Methods 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000002528 anti-freeze Effects 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- MLUCVPSAIODCQM-UHFFFAOYSA-N crotonaldehyde Natural products CC=CC=O MLUCVPSAIODCQM-UHFFFAOYSA-N 0.000 description 3
- 231100000741 direct peptid reactivity assay Toxicity 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 3
- 239000007791 liquid phase Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000012086 standard solution Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 229920003002 synthetic resin Polymers 0.000 description 3
- 239000000057 synthetic resin Substances 0.000 description 3
- SYBYTAAJFKOIEJ-UHFFFAOYSA-N 3-Methylbutan-2-one Chemical compound CC(C)C(C)=O SYBYTAAJFKOIEJ-UHFFFAOYSA-N 0.000 description 2
- PFCHFHIRKBAQGU-UHFFFAOYSA-N 3-hexanone Chemical compound CCCC(=O)CC PFCHFHIRKBAQGU-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- HYTRYEXINDDXJK-UHFFFAOYSA-N Ethyl isopropyl ketone Chemical compound CCC(=O)C(C)C HYTRYEXINDDXJK-UHFFFAOYSA-N 0.000 description 2
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 235000002597 Solanum melongena Nutrition 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000012159 carrier gas Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 230000009965 odorless effect Effects 0.000 description 2
- XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- 238000005191 phase separation Methods 0.000 description 2
- 239000012088 reference solution Substances 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- FZIIBDOXPQOKBP-UHFFFAOYSA-N 2-methyloxetane Chemical compound CC1CCO1 FZIIBDOXPQOKBP-UHFFFAOYSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- PMZXXNPJQYDFJX-UHFFFAOYSA-N acetonitrile;2,2,2-trifluoroacetic acid Chemical compound CC#N.OC(=O)C(F)(F)F PMZXXNPJQYDFJX-UHFFFAOYSA-N 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 150000001339 alkali metal compounds Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SEPQTYODOKLVSB-UHFFFAOYSA-N beta-methylcrotonaldehyde Natural products CC(C)=CC=O SEPQTYODOKLVSB-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- JARKCYVAAOWBJS-UHFFFAOYSA-N hexanal Chemical compound CCCCCC=O JARKCYVAAOWBJS-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
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- 230000007794 irritation Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
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- 244000005700 microbiome Species 0.000 description 1
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- 239000012074 organic phase Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
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- 150000003839 salts Chemical class 0.000 description 1
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- 231100000419 toxicity Toxicity 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/74—Separation; Purification; Use of additives, e.g. for stabilisation
- C07C29/76—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment
- C07C29/86—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment by liquid-liquid treatment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C31/00—Saturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C31/18—Polyhydroxylic acyclic alcohols
- C07C31/20—Dihydroxylic alcohols
- C07C31/207—1,4-Butanediol; 1,3-Butanediol; 1,2-Butanediol; 2,3-Butanediol
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/74—Separation; Purification; Use of additives, e.g. for stabilisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/74—Separation; Purification; Use of additives, e.g. for stabilisation
- C07C29/76—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C31/00—Saturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C31/18—Polyhydroxylic acyclic alcohols
- C07C31/20—Dihydroxylic alcohols
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N2030/022—Column chromatography characterised by the kind of separation mechanism
- G01N2030/027—Liquid chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/86—Signal analysis
- G01N30/8624—Detection of slopes or peaks; baseline correction
Definitions
- the present invention relates to a product 1,3-butylene glycol that is useful as a raw material for synthetic resins, a raw material for surfactants, a solvent, an antifreeze liquid, a raw material for cosmetics, and the like.
- 1,3-butylene glycol is a viscous, colorless, transparent, low-odor liquid with a boiling point of 208°C and excellent chemical stability. Therefore, 1,3-butylene glycol is used as a raw material for various synthetic resins and surfactants. 1,3-Butylene glycol is also used as a material for cosmetics, moisture absorbents, high boiling point solvents, and antifreeze, taking advantage of its excellent hygroscopic properties, low volatility, and low toxicity. Especially in recent years, the demand for 1,3-butylene glycol, which is low in toxicity and irritation, has been greatly increased in the cosmetics industry because of its excellent properties as a moisturizing agent.
- Patent Document 1 discloses 1,3-butylene glycol with low odor. Furthermore, as a method for obtaining 1,3-butylene glycol with little odor, crude 1,3-butylene glycol is mixed with water and an organic solvent, phase-separated into an aqueous layer and an organic layer, and then 1,3-butylene A method for producing 1,3-butylene glycol is disclosed which includes the step of obtaining an aqueous layer containing glycol. According to the production method of the document, ketones are preferred as the organic solvent used as the extractant, and methyl isobutyl ketone is more preferred.
- the object of the present invention is to provide a 1,3-butylene glycol product that is odorless, does not generate odor over time, and has reduced skin sensitization.
- the present inventors found that the above problems can be solved by suppressing the concentration of specific impurities contained in 1,3-butylene glycol to a certain level or less, and completed the present invention.
- the present invention is as follows. [1] In the HPLC analysis under the following conditions after the preparation of the sample below, when the relative retention time of 2,4-dinitrophenylhydrazine is 1.0, the peak appears in the range of relative retention time 4.4 to 12.0 The sum of the absorbance area values is 1000 or less, A product 1,3-butylene glycol containing a dinitrophenylhydrazine derivative of a carbonyl compound having 4 to 6 carbon atoms as a component corresponding to the peak appearing in the range of the relative retention time of 4.4 to 12.0.
- sample preparation 1000 ⁇ L of a solution obtained by adding 5 mL of acetonitrile to a 2,4-dinitrophenylhydrazine cartridge (InertSep mini AERO DNPH, GL Sciences Inc.) to extract 2,4-dinitrophenylhydrazine and 100 ⁇ L of 0.2 mol/L hydrochloric acid; , 0.05 g of 3-butylene glycol, and reacted at 45° C. for 2 hours.
- HPLC analysis conditions Measurement sample: The reaction solution obtained by the above sample preparation is diluted to 2 mL with a mobile phase used in HPLC, and this diluted solution is used as a measurement sample.
- 1,3-butylene glycol as a product that is odorless, does not generate odor over time, and has reduced skin sensitization.
- the product 1,3-butylene glycol according to the present embodiment has a relative retention of 2,4-dinitrophenylhydrazine when the relative retention time of 2,4-dinitrophenylhydrazine is 1.0 in HPLC analysis under the following conditions after the preparation of the sample described below.
- the sum of the absorbance area values of the peaks appearing in the range of 4.4 to 12.0 for the time is 1000 or less, and the component corresponding to the peak appearing in the range of 4.4 to 12.0 for the relative retention time is carbon
- the dinitrophenylhydrazine derivative of a carbonyl compound having 4 to 6 carbon atoms is obtained by converting a carbonyl compound having 4 to 6 carbon atoms contained in 1,3-butylene glycol or its acetal compound into 2,4-dinitrophenylhydrazine (hereinafter referred to as Also referred to as "DNPH").
- DNPH 2,4-dinitrophenylhydrazine
- the peak of the derivative has a relative retention time of 4.4 to 12.0 when the relative retention time of the DNPH peak is 1.0. appear.
- the measurement conditions for the HPLC analysis in this embodiment are as follows.
- Sample preparation 1000 ⁇ L of a solution obtained by adding 5 mL of acetonitrile to a 2,4-dinitrophenylhydrazine cartridge (InertSep mini AERO DNPH, GL Sciences Inc.) to extract 2,4-dinitrophenylhydrazine and 100 ⁇ L of 0.2 mol/L hydrochloric acid; , 0.05 g of 3-butylene glycol, and reacted at 45° C. for 2 hours.
- Sample preparation 1000 ⁇ L of a solution obtained by adding 5 mL of acetonitrile to a 2,4-dinitrophenylhydrazine cartridge (InertSep mini AERO DNPH, GL Sciences Inc.) to extract 2,4-dinitrophenylhydrazine and 100 ⁇ L of 0.2 mol/L hydrochloric acid; , 0.05 g of 3-butylene glycol, and reacted
- Detector UV-Vis detector Detection wavelength: 369 nm
- the peak appearing in the range of relative retention time 4.4 to 12.0 at 369 nm by ultraviolet spectrophotometer Measure the area value of the absorbance at .
- the product 1,3-butylene glycol of the present embodiment has a relative retention time of 4.4 to 12.0 when the relative retention time of 2,4-dinitrophenylhydrazine is 1.0 in the above HPLC analysis.
- the sum of area values of absorbance of peaks appearing in the range (hereinafter also referred to as "sum of peak area values”) is 1000 or less. Odor generation and skin sensitization are reduced when the sum of the peak area values is 1000 or less.
- the sum of the peak area values is preferably 800 or less, more preferably 500 or less, and even more preferably 400 or less, from the viewpoint that the effect of the present invention becomes more pronounced.
- the lower limit of the sum of the peak area values is not particularly limited, it may be 1 or more, or may be 10 or more, for example, from the viewpoint of manufacturing cost.
- the product 1,3-butylene glycol of the present embodiment contains a dinitrophenyl hydrazine derivative of a carbonyl compound having 4 to 6 carbon atoms as a component corresponding to the peak appearing in the relative retention time range of 4.4 to 12.0.
- carbonyl compounds having 4 to 6 carbon atoms include methyl ethyl ketone, methyl vinyl ketone, crotonaldehyde, butyraldehyde, isobutyraldehyde, methyl propyl ketone, methyl isopropyl ketone, diethyl ketone, 2-hexanone, and 6-hexene-2-one.
- the 1,3-butylene glycol product of the present embodiment preferably contains a small amount of carbonyl compounds having 4 to 6 carbon atoms as impurities.
- Examples of the method for confirming the relative retention time of the dinitrophenylhydrazine derivative of the carbonyl compound having 4 to 6 carbon atoms in the above HPLC analysis include the following method.
- the area ratio of the 1,3-butylene glycol peak in gas chromatography analysis (hereinafter also referred to as GC analysis) under the following conditions is not particularly limited, but is required. For example, it is preferably 99.6% or more, more preferably 99.7% or more, even more preferably 99.8% or more, and particularly preferably 99.9% or more, depending on the product quality.
- the "area ratio" of a peak means the ratio of the area of a specific peak to the sum of the areas of all peaks appearing on the chart.
- all peaks refer to all peaks that appear when analysis is continued until the relative retention time of 2.2 is stopped, when the relative retention time of the 1,3-butylene glycol peak is set to 1.0. means. Odor generation and skin sensitization tend to be further reduced when the area ratio of the peak is within the above range.
- Measurement conditions for gas chromatography analysis in the present embodiment are preferably as follows.
- Analyzer 7890B Gas Chromatography System manufactured by Agilent Technologies Analysis column: DB-WAX manufactured by Agilent Technologies (length 30 m ⁇ inner diameter 0.25 mm ⁇ film thickness 0.25 ⁇ m)
- Temperature rising conditions After heating from 80°C to 230°C at 5°C/min, hold at 230°C for 10 minutes
- Carrier gas Nitrogen column gas flow rate: 0.5 mL/min Detector and detection temperature: Flame ionization detector (FID), 250°C Control Mode: Constant Flow Split Ratio: 50:1 Sample injection conditions: 1 ⁇ L
- skin sensitization test The product 1,3-butylene glycol in this embodiment has reduced skin sensitization.
- skin sensitization refers to the occurrence of allergic reactions after skin contact.
- Experimental animals have usually been used to evaluate skin sensitization, but in 2015 the OECD guideline TG442C adopted an in-Chemico peptide binding assay (DPRA) as an alternative test from the perspective of animal welfare.
- DPRA in-Chemico peptide binding assay
- skin sensitization is evaluated by a test applying DPRA. More specifically, skin sensitization is evaluated according to the method described in the Examples below.
- the crude 1,3-butylene glycol used as a raw material when producing the product 1,3-butylene glycol in the present embodiment is not particularly limited, but for example, 1,3-butylene that gives off an odor Glycol or 1,3-butylene glycol, whose odor increases over time, and the like.
- 1,3-butylene glycol and the like, which have skin sensitization, may also be used.
- the peak area ratio of 1,3-butylene glycol in the gas chromatography analysis under the above-mentioned specific conditions is the amount of impurities contained in the product 1,3-butylene glycol. From the viewpoint of reduction, it is preferably 99.5% or more, more preferably 99.6% or more, and still more preferably 99.7% or more.
- the method for producing crude 1,3-butylene glycol as a raw material is not particularly limited. 3-butylene glycol can be produced. Also, those produced by the liquid phase hydrogen reduction method of acetaldol, those produced by the hydrolysis method of 1,3-butylene oxide, those produced by fermentation methods using microorganisms or fungi, and mixtures thereof etc., may be used. Among them, it is preferable to use the reaction product obtained by the liquid-phase hydrogen reduction method of acetaldol, because the effect of the present invention tends to be more remarkable.
- odor-causing substances include substances that themselves are odor sources, substances that become odor substances due to aging, heat treatment, chemical treatment, and the like.
- reaction product obtained by the hydrogen reduction method of acetaldol may be used after alcohols such as ethanol, which are by-products, salts, moisture, etc. have been removed.
- alcohols such as ethanol
- the method for removing these components is not limited, and methods such as distillation and adsorption can be used.
- the method for producing the product 1,3-butylene glycol in the present embodiment is not particularly limited.
- a step of distilling off water from the aqueous layer containing glycol (dehydration distillation step), and a step of distilling off low boiling point components from 1,3-butylene glycol after distilling off the water (removal of low boiling point distillation step). can be used.
- Each step will be described below.
- the heat treatment step in the method for producing 1,3-butylene glycol product of the present embodiment is a step of heat-treating crude 1,3-butylene glycol.
- thermal decomposition of highly polar impurities such as carbonyl compounds having 4 to 6 carbon atoms, which are highly compatible with 1,3-butylene glycol, progresses, and moderately polar impurities Since it becomes a dehydration condensate or an acetal compound, it is presumed to be efficiently removed in the subsequent extraction step.
- the mechanism of the present invention is not limited to the above.
- the heating time in the heat treatment step is not particularly limited, but is preferably 20 minutes to 9 hours, more preferably 1 to 6 hours, still more preferably 1 to 3 hours.
- the heating time is 20 minutes or more, thermal decomposition of highly polar impurities tends to proceed sufficiently, and when it is 9 hours or less, an increase in the cost of heat treatment tends to be suppressed.
- the heating temperature in the heat treatment step is not particularly limited, but is preferably 120 to 200°C, more preferably 130 to 170°C, and still more preferably 140 to 160°C.
- the heating temperature is 120° C. or higher, thermal decomposition of highly polar impurities tends to proceed sufficiently, and when it is 200° C. or lower, the thermal decomposition reaction of 1,3-butylene glycol is suppressed, and impurities are reduced. There is a tendency.
- the heat treatment apparatus in the heat treatment step is not particularly limited, and examples thereof include heat treatment apparatuses such as a continuous tube type, a batch type tank type, and a continuous tank type. Therefore, the batch type tank type is particularly preferable.
- the extraction step in the method for producing 1,3-butylene glycol product of the present embodiment includes mixing the crude 1,3-butylene glycol after the heat treatment with water and an organic solvent, and phase-separating the aqueous layer and the organic layer. , to obtain an aqueous layer containing 1,3-butylene glycol.
- organic solvents include aliphatic hydrocarbons such as hexane and heptane, cycloaliphatic hydrocarbons such as cyclohexane and methylcyclohexane, aromatic hydrocarbons such as toluene and xylene, diethyl ether and dibutyl ether.
- organic solvents such as methylene chloride and chloroform; esters such as ethyl acetate and butyl acetate; and ketones such as methyl isobutyl ketone. Hydrocarbons are preferred, and methyl isobutyl ketone or methylcyclohexane are more preferred.
- These organic solvents may be used alone, or two or more may be selected and mixed in an arbitrary ratio.
- the amount of the organic solvent used is preferably 10 to 300 parts by mass, more preferably 20 to 200 parts by mass, based on 100 parts by mass of the crude 1,3-butylene glycol after heat treatment, from the viewpoint of extraction efficiency. is more preferred.
- the amount of water used is preferably 20 to 400 parts by mass, more preferably 40 to 200 parts by mass, based on 100 parts by mass of crude 1,3-butylene glycol after heat treatment, from the viewpoint of extraction efficiency. more preferred.
- the order of adding water and an organic solvent to crude 1,3-butylene glycol after heat treatment is not particularly limited.
- the temperature at which water and an organic solvent are mixed with the crude 1,3-butylene glycol after heat treatment is not particularly limited, but from the viewpoint of extraction efficiency, the temperature is preferably between 5 and 80°C, preferably between 10 and 50°C. More preferably the temperature is between °C.
- Mixing of the heat-treated crude 1,3-butylene glycol with water and an organic solvent can be carried out, for example, in a batch system or a continuous system.
- water and an organic solvent are placed in a mixing vessel, and after stirring for preferably 10 seconds to 2 hours, preferably static for 1 minute to 2 hours. and phase separation to obtain an aqueous layer containing 1,3-butylene glycol.
- An organic solvent is further added to the resulting aqueous layer containing 1,3-butylene glycol, the mixture is stirred, and after phase separation, the operation of obtaining an aqueous layer containing 1,3-butylene glycol may be repeated.
- the number of times is preferably 1 to 3 times.
- the amount of the organic solvent to be added is preferably 10 to 300 parts by mass per 100 parts by mass of crude 1,3-butylene glycol after heat treatment.
- an apparatus generally used for continuous extraction, etc. such as a combination of a mixer and a settler, a spray tower, a packed tower, a plate tower, etc., can be used. It is preferable to use the above packed tower or tray tower.
- the dehydration distillation step in the method for producing 1,3-butylene glycol product of the present embodiment is a step of distilling off water from the aqueous layer containing 1,3-butylene glycol obtained in the extraction step.
- the distillation apparatus used in the dehydration distillation step includes, for example, a perforated plate tower, a bubble cap tower, a packed tower, etc. Among them, a packed tower having a theoretical plate number of 7 to 40 is preferable.
- One distillation column may be used, or two or more columns may be used.
- the low boiling point distillation step in the method for producing 1,3-butylene glycol of the present embodiment is a step of distilling off low boiling point components from the 1,3-butylene glycol obtained in the dehydration distillation step.
- Distillation apparatuses used in the low-boiling point distillation step include, for example, a perforated plate tower, a bubble cap tower, a packed tower, etc. Among them, a packed tower having a theoretical plate number of 7 to 40 is preferable.
- One distillation column may be used, or two or more columns may be used.
- 1,3-butylene glycol (product name: 1,3-butylene glycol) manufactured by KH Neochem Co., Ltd. was used. Moreover, various analyzes and evaluations were performed according to the following.
- HPLC analysis of the product 1,3-butylene glycol was performed under the following conditions. (Conditions for HPLC analysis) Sample preparation: 1000 ⁇ L of a solution obtained by adding 5 mL of acetonitrile to a 2,4-dinitrophenylhydrazine cartridge (InertSep mini AERO DNPH, GL Sciences Inc.) to extract 2,4-dinitrophenylhydrazine, and 100 ⁇ L of 0.2 mol/L hydrochloric acid. , and 0.05 g of 1,3-butylene glycol, and reacted at 45° C. for 2 hours.
- Sample preparation 1000 ⁇ L of a solution obtained by adding 5 mL of acetonitrile to a 2,4-dinitrophenylhydrazine cartridge (InertSep mini AERO DNPH, GL Sciences Inc.) to extract 2,4-dinitrophenylhydrazine, and 100 ⁇ L of 0.2 mol/L hydrochloric acid
- the reaction solution was diluted to 2 mL with a mobile phase used in HPLC, and this diluted solution was used as a measurement sample.
- Analyzer Agilent 1200 Series manufactured by Agilent Technologies Detector: Agilent 1200 Series UV-Vis detector G1314B manufactured by Agilent Technologies Detection wavelength: 369 nm
- the said test is called a "smell return test.” ⁇ Rating A 10% by weight aqueous solution of 1,3-butylene glycol manufactured by KH Neochem Co., Ltd. was used as a standard odor sample, and the sample was rated as 5. A score of 1 was given when no odor was perceived, and a score of 2 to 4 was given in the interval between them according to the following. 1: No odor 2: Faint odor 3: Weak odor 4: Odor 5: Clear odor
- sample solution 1 Two hours after the standard solution was prepared, 750 ⁇ L of the peptide solution, 200 ⁇ L of acetonitrile, and 50 ⁇ L of 1,3-butylene glycol were placed in another brown sample bottle for HPLC to prepare a sample solution (sample solution 1). . After 4 hours and 6 hours from the preparation of the reference solution, specimen solutions were prepared in the same manner (specimen solution 2 and specimen solution 3). For each of the three standard solutions and sample solutions (sample solution 1, sample solution 2, sample solution 3), measurement was performed by HPLC analysis after 72 ⁇ 2 hours had passed since each solution was prepared. Three average peak heights of the peptides were calculated respectively. The peptide reduction rate was calculated using the following formula (1) from the calculated 3-time average value.
- Peptide reduction rate (%) (3 times average value of peptide peak height in sample solution/3 times average value of peptide peak height in reference solution) ⁇ 100 (1) The operations from the preparation of the peptide solution to the measurement by HPLC analysis were performed three times in total, and the average value of the peptide reduction rate calculated for three times was used as the evaluation result. In addition, from the viewpoint of reproducibility in this test, a sample of 1,3-butylene glycol for comparison was tested on the same day.
- Example 1 Heat treatment process 100 g of 1,3-butylene glycol manufactured by KH Neochem Co., Ltd. was placed in a three-necked flask and heat-treated at an oil bath temperature of 160° C. for 1 hour.
- the obtained product 1,3-butylene glycol was subjected to HPLC analysis under the measurement conditions described above. there were. Further, it was confirmed by the above confirmation method that the dinitrophenylhydrazine derivative of the carbonyl compound having 4 to 6 carbon atoms was included as the component corresponding to the peak appearing in the range of relative retention time of 4.4 to 12.0. As a result of GC analysis under the above measurement conditions, the peak area ratio of 1,3-butylene glycol was 99.71%. When the product 1,3-butylene glycol was subjected to an odor test, the score was 1 for odor and 2 for return of odor. Further, when a skin sensitization test was conducted, the peptide reduction rate average of 3 times was 6.6%. These results are shown in Table 1 for the product 1,3-butylene glycol.
- Example 2 The extraction process was carried out in the same manner as in Example 1 except that methyl isobutyl ketone was used as the extractant in the extraction process and the temperature in the heat treatment process was 140°C.
- the obtained product 1,3-butylene glycol was subjected to HPLC analysis under the measurement conditions described above. there were. Further, it was confirmed by the above confirmation method that the dinitrophenylhydrazine derivative of the carbonyl compound having 4 to 6 carbon atoms was included as the component corresponding to the peak appearing in the range of relative retention time of 4.4 to 12.0. As a result of GC analysis under the above measurement conditions, the peak area ratio of 1,3-butylene glycol was 99.87%.
- Example 1 The procedure was carried out in the same manner as in Example 1, except that methyl isobutyl ketone was used as the extracting agent in the extraction step without carrying out the hydration treatment step and the low boiling point distillation step. Details are shown below.
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Abstract
Description
また、化粧品分野において1,3-ブチレングリコールを使用する際には、皮膚に直接塗布するが、特許文献1に記載された方法で得られる1,3-ブチレングリコールは、皮膚感作性を十分に低減できていないという問題もある。
[1]
下記試料調製実施後の下記条件下におけるHPLC分析において、2,4-ジニトロフェニルヒドラジンの相対保持時間を1.0としたときに、相対保持時間が4.4~12.0の範囲に現れるピークの吸光度の面積値の和が1000以下であり、
前記相対保持時間が4.4~12.0の範囲に現れるピークに該当する成分として炭素数4~6のカルボニル化合物のジニトロフェニルヒドラジン誘導体を含む、製品1,3-ブチレングリコール。
[試料調製]
2,4-ジニトロフェニルヒドラジンカートリッジ(InertSep mini AERO DNPH、GL Sciences Inc.)にアセトニトリル5mLを加えて2,4-ジニトロフェニルヒドラジンを抽出した溶液1000μLと、0.2mol/L塩酸100μLを、製品1,3-ブチレングリコール0.05gに加えて45℃で2時間反応を行う。
[HPLC分析の条件]
測定試料:前記試料調製によって得られる反応液を、HPLCにて使用する移動相で2mLに希釈し、この希釈液を測定試料とする。
検出器:UV-Vis検出器
検出波長:369nm
分析カラム:パルミットアミドプロピル基修飾のシリカゲル(粒子径5μm、内径×長さ=4.6mm×25cm、ポアサイズ100Å、表面被覆率2.7μmol/m2、表面積450m2/g、金属不純物5ppm未満、カーボン含量19.5%)を固定相としたカラム
移動相:アセトニトリル/蒸留水=50/50(vol比)
移動相流量:0.4mL/min
試料注入量:20μL
[2]
前記相対保持時間が4.4~12.0の範囲に現れるピークの吸光度の面積値の和が800以下である、上記[1]記載の製品1,3-ブチレングリコール。
[3]
前記相対保持時間が4.4~12.0の範囲に現れるピークの吸光度の面積値の和が500以下である、上記[1]記載の製品1,3-ブチレングリコール。
なお、本実施形態においては、最終製品である1,3-ブチレングリコールを「製品1,3-ブチレングリコール」、原料としての1,3-ブチレングリコールを「粗1,3-ブチレングリコール」とも言う。
ここで、炭素数4~6のカルボニル化合物のジニトロフェニルヒドラジン誘導体は、1,3-ブチレングリコールに含まれる炭素数4~6のカルボニル化合物またはそのアセタール化合物を2,4-ジニトロフェニルヒドラジン(以下、「DNPH」とも言う。)により誘導化した化合物である。また、この化合物は、後述する特定条件でのHPLC分析において、当該誘導体のピークはDNPHのピークの相対保持時間を1.0としたとき、相対保持時間が4.4~12.0の範囲に現れる。
[試料調製]
2,4-ジニトロフェニルヒドラジンカートリッジ(InertSep mini AERO DNPH、GL Sciences Inc.)にアセトニトリル5mLを加えて2,4-ジニトロフェニルヒドラジンを抽出した溶液1000μLと、0.2mol/L塩酸100μLを、製品1,3-ブチレングリコール0.05gに加えて45℃で2時間反応を行う。
[HPLC分析の条件]
測定試料:前記試料調製によって得られる反応液を、HPLCにて使用する移動相で2mLに希釈し、この希釈液を測定試料とする。
検出器:UV-Vis検出器
検出波長:369nm
分析カラム:パルミットアミドプロピル基修飾のシリカゲル(粒子径5μm、内径×長さ=4.6mm×25cm、ポアサイズ100Å、表面被覆率2.7μmol/m2、表面積450m2/g、金属不純物5ppm未満、カーボン含量19.5%)を固定相としたカラム
分析条件:カラム温度 40℃
移動相:アセトニトリル/蒸留水=50/50(vol比)
移動相流量:0.4mL/min
試料注入量:20μL
ここで、分析カラムとしては、例えば、Merck社製SUPELCO(登録商標) Ascentis(登録商標) RP-Amide(粒子径5μm、内径×長さ=4.6mm×25cm)を用いることができる。
上記HPLC分析において、炭素数4~6のカルボニル化合物のジニトロフェニルヒドラジン誘導体の相対保持時間を確認する方法として、例えば、以下の方法が挙げられる。市販されている東京化成工業(株)製のメチルビニルケトン、東京化成工業(株)製のクロトンアルデヒド、あるいは富士フイルム和光純薬(株)製の2-ヘキサノンを、KHネオケム(株)製1,3-ブチレングリコールで希釈した溶液0.05gに、0.2mol/L塩酸100μLと、DNPHカートリッジ(InertSep mini AERO DNPH、GL Sciences Inc.)にアセトニトリル5mLを加えて抽出した溶液1000μLとを加えて、45℃で2時間反応を行い、得られた反応液をHPLCにて使用する移動相で2mLに希釈し、この希釈液を上記条件のHPLC分析にて20μL注入して測定することによって、検出されるメチルビニルケトン、クロトンアルデヒド、あるいは2-ヘキサノンのジニトロフェニルヒドラジン誘導体のピークの相対保持時間を確認することができる。
[ガスクロマトグラフィー分析の条件]
分析装置:Agilent Technologies社製 7890B ガスクロマトグラフィーSystem
分析カラム:Agilent Technologies社製 DB-WAX (長さ30m×内径0.25mm×膜厚0.25μm)
昇温条件:5℃/分で80℃から230℃まで昇温した後、230℃で10分間保持
試料導入温度:250℃
キャリアガス:窒素
カラムのガス流量:0.5mL/分
検出器及び検出温度:水素炎イオン化検出器(FID)、250℃
コントロールモード:コンスタントフロー
スプリット比:50:1
試料注入条件:1μL
本実施形態における製品1,3-ブチレングリコールは、皮膚感作性が低減されたものである。ここで皮膚感作性とは、皮膚接触後にアレルギー反応を引き起こすことをいう。皮膚感作性の評価には、通常、実験動物が使用されてきたが、動物福祉の観点から2015年にOECDガイドラインTG442Cでin Chemico試験であるペプチド結合性試験(DPRA)が代替試験として採択されており、本実施形態においても、DPRAを準用した試験により皮膚感作性を評価する。より詳細には、後述する実施例に記載された方法に従って皮膚感作性を評価する。
(原料)
本実施形態における製品1,3-ブチレングリコールを製造する際に原料として使用される粗1,3-ブチレングリコールとしては、特に限定されることはないが、例えば、臭気を感じる1,3-ブチレングリコール又は経時的に臭気が増加する1,3-ブチレングリコール等が挙げられる。あるいは、皮膚感作性を有する1,3-ブチレングリコール等も挙げられる。
本実施形態の製品1,3-ブチレングリコールの製造方法における加熱処理工程は、粗1,3-ブチレングリコールを加熱処理する工程である。粗1,3-ブチレングリコールを加熱処理することにより、1,3-ブチレングリコールとの相溶性の高い炭素数4~6のカルボニル化合物などの高極性の不純物の加熱分解が進行し、中極性の脱水縮合物やアセタール化合物となるため、その後の抽出工程において効率的に除去されると推測される。但し、本発明のメカニズムは上記に限定されることはない。
本実施形態の製品1,3-ブチレングリコールの製造方法における抽出工程は、加熱処理後の粗1,3-ブチレングリコールを水及び有機溶媒と混合し、水層と有機層に相分離させた後、1,3-ブチレングリコールを含む水層を得る工程である。ここで、有機溶媒としては、例えば、ヘキサン、ヘプタン等の脂肪族炭化水素類、シクロヘキサン、メチルシクロヘキサン等の環状脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、ジエチルエーテル、ジブチルエーテル等のエーテル類、塩化メチレン、クロロホルム等の有機塩素化物類、酢酸エチル、酢酸ブチル等のエステル類、メチルイソブチルケトン等のケトン類等があげられ、中でも不純物除去の観点からケトン類あるいは環状脂肪族炭化水素が好ましく、メチルイソブチルケトンあるいはメチルシクロヘキサンがより好ましい。これらの有機溶媒は単独で用いてもよいし、2種以上を選択して任意の比で混合して用いてもよい。有機溶媒の使用量は、加熱処理後の粗1,3-ブチレングリコール100質量部に対して、抽出効率の観点から、10~300質量部であることが好ましく、20~200質量部であることがより好ましい。
本実施形態の製品1,3-ブチレングリコールの製造方法における脱水蒸留工程は、抽出工程で得た1,3-ブチレングリコールを含む水層から水を留去する工程である。脱水蒸留工程において用いる蒸留装置としては、例えば、多孔板塔、泡鐘塔、充填塔等が挙げられるが、中でも、理論段数が7~40段の充填塔が好ましい。蒸留塔は、1塔でもよいし、2塔以上のものを用いてもよい。蒸留の条件としては、蒸留塔の塔頂部の圧力が5~20kPaであることが好ましく、蒸留塔の塔底部の温度が120~160℃であることが好ましく、135~155℃であることがより好ましい。脱水蒸留工程の具体的な態様としては、例えば、1,3-ブチレングリコールを含む水層を蒸留塔の塔頂より連続的に供給し、塔頂より水を多く含む留分を連続的に抜き出すと同時に、塔底より1,3-ブチレングリコールを連続的に抜き出す方法等が挙げられる。
本実施形態の1,3-ブチレングリコールの製造方法における脱低沸蒸留工程は、脱水蒸留工程で得た1,3-ブチレングリコールから低沸点成分を留去する工程である。脱低沸蒸留工程において用いる蒸留装置としては、例えば、多孔板塔、泡鐘塔、充填塔等が挙げられるが、中でも、理論段数が7~40段の充填塔が好ましい。蒸留塔は、1塔でもよいし、2塔以上のものを用いてもよい。蒸留の条件としては、蒸留塔の塔頂部の圧力が1~20kPaであることが好ましく、蒸留塔の塔底部の温度が100~160℃であることが好ましく、110~140℃であることがより好ましい。脱低沸蒸留工程の具体的な態様としては、例えば、1,3-ブチレングリコールを蒸留塔の塔頂より連続的に供給し、塔頂より低沸点分を多く含む留分を連続的に抜き出すと同時に、塔底より1,3-ブチレングリコールを連続的に抜き出す方法等が挙げられる。
本実施形態における1,3-ブチレングリコールの製造方法としては、上記各工程の好ましい範囲を組み合わせた方法であることが好ましい。
以下の条件で、製品1,3-ブチレングリコールのHPLC分析を行った。
(HPLC分析の条件)
試料調製:2,4-ジニトロフェニルヒドラジンカートリッジ(InertSep mini AERO DNPH、GL Sciences Inc.)にアセトニトリル5mLを加えて2,4-ジニトロフェニルヒドラジンを抽出した溶液1000μLと、0.2mol/L塩酸100μLを、1,3-ブチレングリコール0.05gに加えて45℃で2時間反応を行った。当該反応液をHPLCにて使用する移動相で2mLに希釈し、この希釈液を測定試料とした。
分析装置:Agilent Technologies社製 Agilent 1200Series
検出器:Agilent Technologies社製 Agilent 1200Series UV-Vis検出器 G1314B
検出波長:369nm
分析カラム:Merck社製SUPELCO(登録商標) Ascentis(登録商標)RP-Amide(粒子径5μm、内径×長さ=4.6mm×25cm)
分析条件:カラム温度40℃
移動相:アセトニトリル/蒸留水=50/50(vol比)
移動相流量:0.4mL/min
試料注入条件:20μL
なお、分析カラムとして用いたMerck社製SUPELCO(登録商標) Ascentis(登録商標)RP-Amideは、パルミットアミドプロピル基修飾のシリカゲル(粒子径5μm、内径×長さ=4.6mm×25cm、ポアサイズ100Å、表面被覆率2.7μmol/m2、表面積450m2/g、金属不純物5ppm未満、カーボン含量19.5%)を固定相としたカラムである。
以下の条件で、対象となる製品1,3-ブチレングリコールのガスクロマトグラフィー分析を行った。
(ガスクロマトグラフィー分析の条件)
分析装置:Agilent Technologies社製 7890B ガスクロマトグラフィーSystem
分析カラム:Agilent Technologies社製 DB-WAX (長さ30m×内径0.25mm×膜厚0.25μm)
昇温条件:5℃/分で80℃から230℃まで昇温した後、230℃で10分間保持
試料導入温度:250℃
キャリアガス:窒素
カラムのガス流量:0.5mL/分
検出器及び検出温度:水素炎イオン化検出器(FID)、250℃
コントロールモード:コンスタントフロー
スプリット比:50:1
試料注入条件:1μL
実施例及び比較例で得られた1,3-ブチレングリコールについて、以下の2通りの評価方法に従って臭気試験を行った。
(臭気の評価方法)
1,3-ブチレングリコールの10重量%水溶液10gを20mLの広口ガラス瓶に入れてふたを閉め、室温で1分間激しく撹拌した。ふたを開けて臭気を嗅ぎ、標準臭気サンプルと比較して、試料の臭気レベルを決定した。評価人数は7名とし、各人の評価結果の平均点を算出し、臭気の評点とした。
(におい戻りの評価方法)
1,3-ブチレングリコールの10重量%水溶液10gを20mLの広口ガラス瓶に入れてふたを閉め、50℃で3日間、加熱した。その後、室温まで冷却し、1分間激しく撹拌した。ふたを開けて臭気を嗅ぎ、標準臭気サンプルと比較して、試料の臭気レベルを決定した。評価人数は7名とし、各人の評価結果の平均点を算出し、におい戻りの評点とした。なお、上記試験のことを「におい戻り試験」と呼称する。
・評点
KHネオケム(株)製1,3-ブチレングリコールの10重量%水溶液を標準臭気サンプルとし、サンプルの評点を5とした。臭気を感じない場合を評点1とし、その間を以下に従って評点2~4とした。
1:臭気を感じない
2:微かに臭気を感じる
3:弱い臭気を感じる
4:臭気を感じる
5:明瞭に臭気を感じる
実施例1~2および比較例1で得られた1,3-ブチレングリコールについて、以下の方法に従って皮膚感作性の評価を行った。
(皮膚感作性試験の条件)
スクラム社製DPRA用システイン含有ペプチド15mgと、0.05Mリン酸緩衝液30mLとを混合し、当該ペプチドを0.667mM含有する0.05Mリン酸緩衝液溶液(以下、ペプチド溶液)を調製した。ペプチド溶液を調製してから1時間経過後、3つのHPLC用褐色サンプル瓶のそれぞれに、ペプチド溶液750μLと、アセトニトリル250μLとを入れ、基準溶液を3つ調製した。基準溶液を調製してから2時間経過後、別のHPLC用褐色サンプル瓶に、ペプチド溶液750μLと、アセトニトリル200μLと、1,3-ブチレングリコール50μLとを入れ検体溶液を調製した(検体溶液1)。さらに基準溶液を調製してから4時間経過後および6時間経過後に、同様の操作で検体溶液を調製した(検体溶液2および検体溶液3)。3つの基準溶液と検体溶液(検体溶液1、検体溶液2、検体溶液3)のそれぞれについて、各溶液を調製してから72±2時間経過後にHPLC分析による測定を行い、基準溶液と検体溶液のペプチドのピーク高さの3回平均値をそれぞれ算出した。算出した3回平均値より、下記式(1)を用いてペプチド減少率を算出した。
ペプチド減少率(%)=(検体溶液のペプチドのピーク高さの3回平均値/基準溶液のペプチドのピーク高さの3回平均値)×100 (1)
上記のペプチド溶液調製からHPLC分析による測定までの操作を合計3回実施し、算出したペプチド減少率の3回平均値を評価結果とした。また、本試験は再現性の観点から、比較する製品1,3-ブチレングリコールの検体を同日に試験した。
(皮膚感作性試験におけるHPLC分析の条件)
分析装置:Agilent Technologies社製 Agilent 1260 InfinityII
検出器:Agilent Technologies社製 Agilent 1260 InfinityII UV-Vis検出器 G7114A
検出波長:220nm
分析カラム:Agilent Technologies社製 Zorbax SB-C-18(粒子径3.5μm、内径×長さ=2.1mm×10mm)
カラム温度:30℃
測定時間:20min
移動相:
A 0.1体積%トリフルオロ酢酸水溶液
B 0.085体積%トリフルオロ酢酸アセトニトリル溶液
グラジエント:
A/B=90/10~75/25(10min)
A/B=75/25~10/90(1min)
A/B=10/90(2min)
A/B=10/90~90/10(0.5min)
A/B=90/10(6.5min)
移動相流量:0.35mL/min
試料注入条件:5μL
(加熱処理工程)
KHネオケム(株)製1,3-ブチレングリコール100gを三口フラスコに仕込み、オイルバス温度160℃で1時間、加熱処理を施した。
次に加熱処理工程後の1,3-ブチレングリコール98g、水100g、及びメチルシクロヘキサン100gを500mLセパラブルフラスコに仕込み、温度を10℃とし回転数500回転/分で10分間撹拌後、5分間静置し、水層と有機層に相分離した。分離した水層にさらにメチルシクロヘキサン100gを加え、同様の操作を2回繰り返した。
次に抽出工程後の水層をナスフラスコに仕込み、オイルバス温度150℃、8kPaで30分間、脱水濃縮し、1,3-ブチレングリコールを93g得た。
脱水濃縮後の1,3-ブチレングリコールを20cmのビグリュー分留装置を取り付けた蒸留装置で、オイルバス温度120℃、1.2kPaで脱低沸蒸留を行い、蒸留装置塔頂から仕込み液量に対し、重量率2%分の留出液を留去した。その結果、製品1,3-ブチレングリコール87gを得た。
上述の測定条件に従ってGC分析を行った結果、1,3-ブチレングリコールのピークの面積率は99.71%であった。
製品1,3-ブチレングリコールについて臭気試験を行ったところ、臭気の評点は1、におい戻りの評点は2であった。また、皮膚感作性試験を行ったところ、ペプチド減少率3回平均値は6.6%であった。製品1,3-ブチレングリコールに関するこれらの結果を表1に示す。
抽出工程の抽剤をメチルイソブチルケトンとし、加熱処理工程の温度を140℃としたこと以外は実施例1と同様に行った。得られた製品1,3-ブチレングリコールについて、上述の測定条件に従ってHPLC分析を行った結果、相対保持時間が4.4~12.0の範囲に現れるピークの吸光度の面積値の和は104であった。また、相対保持時間が4.4~12.0の範囲に現れるピークに該当する成分として、炭素数4~6のカルボニル化合物のジニトロフェニルヒドラジン誘導体を含むことを上述の確認方法により確認した。
上述の測定条件に従ってGC分析を行った結果、1,3-ブチレングリコールのピークの面積率は99.87%であった。
製品1,3-ブチレングリコールについて臭気試験を行ったところ、臭気の評点は1、におい戻りの評点は1であった。また、皮膚感作性試験を行ったところ、ペプチド減少率3回平均値は6.2%であった。製品1,3-ブチレングリコールに関するこれらの結果を表1に示す。
加水処理工程と脱低沸蒸留工程を実施せず、抽出工程の抽剤をメチルイソブチルケトンとしたこと以外は実施例1と同様に行った。以下、詳細を示す。
KHネオケム(株)製1,3-ブチレングリコール100g、水100g、及びメチルイソブチルケトン100gを500mLセパラブルフラスコに仕込み、温度10℃とし回転数500回転/分で10分間撹拌後、5分間静置し、水層と有機層に相分離した。分離した水層にさらにメチルイソブチルケトン100gを加え、同様の操作を2回繰り返した。
次に抽出工程で得られた水層をナスフラスコに仕込み、オイルバス温度150℃、8kPaで30分間、脱水濃縮し、1,3-ブチレングリコール79gを得た。
得られた1,3-ブチレングリコールについて臭気試験を行ったところ、臭気の評点は3、におい戻りの評点は4であった。また、皮膚感作性試験を行ったところ、ペプチド減少率3回平均値は8.7%であった。1,3-ブチレングリコールに関するこれらの結果を表1に示す。
Claims (3)
- 下記試料調製実施後の下記条件下におけるHPLC分析において、2,4-ジニトロフェニルヒドラジンの相対保持時間を1.0としたときに、相対保持時間が4.4~12.0の範囲に現れるピークの吸光度の面積値の和が1000以下であり、
前記相対保持時間が4.4~12.0の範囲に現れるピークに該当する成分として炭素数4~6のカルボニル化合物のジニトロフェニルヒドラジン誘導体を含む、製品1,3-ブチレングリコール。
[試料調製]
2,4-ジニトロフェニルヒドラジンカートリッジにアセトニトリル5mLを加えて2,4-ジニトロフェニルヒドラジンを抽出した溶液1000μLと、0.2mol/L塩酸100μLを、製品1,3-ブチレングリコール0.05gに加えて45℃で2時間反応を行う。
[HPLC分析の条件]
測定試料:前記試料調製によって得られる反応液を、HPLCにて使用する移動相で2mLに希釈し、この希釈液を測定試料とする。
検出器:UV-Vis検出器
検出波長:369nm
分析カラム:パルミットアミドプロピル基修飾のシリカゲル(粒子径5μm、内径×長さ=4.6mm×25cm、ポアサイズ100Å、表面被覆率2.7μmol/m2、表面積450m2/g、金属不純物5ppm未満、カーボン含量19.5%)を固定相としたカラム
分析条件:カラム温度 40℃
移動相:アセトニトリル/蒸留水=50/50(vol比)
移動相流量:0.4mL/min
試料注入量:20μL
- 前記相対保持時間が4.4~12.0の範囲に現れるピークの吸光度の面積値の和が800以下である、請求項1記載の製品1,3-ブチレングリコール。
- 前記相対保持時間が4.4~12.0の範囲に現れるピークの吸光度の面積値の和が500以下である、請求項1記載の製品1,3-ブチレングリコール。
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US11952329B2 (en) | 2024-04-09 |
JP2022186191A (ja) | 2022-12-15 |
JP7086254B1 (ja) | 2022-06-17 |
KR20230031982A (ko) | 2023-03-07 |
CN116323531A (zh) | 2023-06-23 |
US20240083830A1 (en) | 2024-03-14 |
TW202313539A (zh) | 2023-04-01 |
KR102558875B1 (ko) | 2023-07-24 |
EP4345087A1 (en) | 2024-04-03 |
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