JP2017043543A - Separation method of 4-hydroxystyrene compound - Google Patents
Separation method of 4-hydroxystyrene compound Download PDFInfo
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- JP2017043543A JP2017043543A JP2015164538A JP2015164538A JP2017043543A JP 2017043543 A JP2017043543 A JP 2017043543A JP 2015164538 A JP2015164538 A JP 2015164538A JP 2015164538 A JP2015164538 A JP 2015164538A JP 2017043543 A JP2017043543 A JP 2017043543A
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- JP
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- Prior art keywords
- ether
- hydroxystyrene
- volatile solvent
- diethylene glycol
- glycol
- Prior art date
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- FUGYGGDSWSUORM-UHFFFAOYSA-N para-hydroxystyrene Natural products OC1=CC=C(C=C)C=C1 FUGYGGDSWSUORM-UHFFFAOYSA-N 0.000 title claims abstract description 75
- -1 4-hydroxystyrene compound Chemical class 0.000 title claims abstract description 46
- 238000000926 separation method Methods 0.000 title claims abstract description 16
- 239000002904 solvent Substances 0.000 claims abstract description 38
- 238000004821 distillation Methods 0.000 claims abstract description 19
- 239000010409 thin film Substances 0.000 claims abstract description 17
- 238000006243 chemical reaction Methods 0.000 claims abstract description 12
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims description 17
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 claims description 16
- QHJGZUSJKGVMTF-UHFFFAOYSA-N canolol Chemical compound COC1=CC(C=C)=CC(OC)=C1O QHJGZUSJKGVMTF-UHFFFAOYSA-N 0.000 claims description 14
- 238000006116 polymerization reaction Methods 0.000 claims description 14
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 14
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 12
- 239000003112 inhibitor Substances 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 10
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical group CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 9
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims description 9
- RGHHSNMVTDWUBI-UHFFFAOYSA-N para-hydroxybenzaldehyde Natural products OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 claims description 9
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 9
- 229960000984 tocofersolan Drugs 0.000 claims description 9
- 239000001087 glyceryl triacetate Substances 0.000 claims description 8
- 235000013773 glyceryl triacetate Nutrition 0.000 claims description 8
- 229960002622 triacetin Drugs 0.000 claims description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims description 6
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 claims description 6
- 229940028356 diethylene glycol monobutyl ether Drugs 0.000 claims description 6
- HJOVHMDZYOCNQW-UHFFFAOYSA-N isophorone Chemical compound CC1=CC(=O)CC(C)(C)C1 HJOVHMDZYOCNQW-UHFFFAOYSA-N 0.000 claims description 6
- JCGNDDUYTRNOFT-UHFFFAOYSA-N oxolane-2,4-dione Chemical compound O=C1COC(=O)C1 JCGNDDUYTRNOFT-UHFFFAOYSA-N 0.000 claims description 6
- ZUHZGEOKBKGPSW-UHFFFAOYSA-N tetraglyme Chemical compound COCCOCCOCCOCCOC ZUHZGEOKBKGPSW-UHFFFAOYSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 5
- 229940087168 alpha tocopherol Drugs 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 235000004835 α-tocopherol Nutrition 0.000 claims description 5
- 239000002076 α-tocopherol Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 4
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 claims description 3
- GDXHBFHOEYVPED-UHFFFAOYSA-N 1-(2-butoxyethoxy)butane Chemical compound CCCCOCCOCCCC GDXHBFHOEYVPED-UHFFFAOYSA-N 0.000 claims description 3
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 claims description 3
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 claims description 3
- FPZWZCWUIYYYBU-UHFFFAOYSA-N 2-(2-ethoxyethoxy)ethyl acetate Chemical compound CCOCCOCCOC(C)=O FPZWZCWUIYYYBU-UHFFFAOYSA-N 0.000 claims description 3
- SBASXUCJHJRPEV-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanol Chemical compound COCCOCCO SBASXUCJHJRPEV-UHFFFAOYSA-N 0.000 claims description 3
- WFSMVVDJSNMRAR-UHFFFAOYSA-N 2-[2-(2-ethoxyethoxy)ethoxy]ethanol Chemical compound CCOCCOCCOCCO WFSMVVDJSNMRAR-UHFFFAOYSA-N 0.000 claims description 3
- WAEVWDZKMBQDEJ-UHFFFAOYSA-N 2-[2-(2-methoxypropoxy)propoxy]propan-1-ol Chemical compound COC(C)COC(C)COC(C)CO WAEVWDZKMBQDEJ-UHFFFAOYSA-N 0.000 claims description 3
- NQBXSWAWVZHKBZ-UHFFFAOYSA-N 2-butoxyethyl acetate Chemical compound CCCCOCCOC(C)=O NQBXSWAWVZHKBZ-UHFFFAOYSA-N 0.000 claims description 3
- CRWNQZTZTZWPOF-UHFFFAOYSA-N 2-methyl-4-phenylpyridine Chemical compound C1=NC(C)=CC(C=2C=CC=CC=2)=C1 CRWNQZTZTZWPOF-UHFFFAOYSA-N 0.000 claims description 3
- CUZKCNWZBXLAJX-UHFFFAOYSA-N 2-phenylmethoxyethanol Chemical compound OCCOCC1=CC=CC=C1 CUZKCNWZBXLAJX-UHFFFAOYSA-N 0.000 claims description 3
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 3
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 3
- UBPGILLNMDGSDS-UHFFFAOYSA-N diethylene glycol diacetate Chemical compound CC(=O)OCCOCCOC(C)=O UBPGILLNMDGSDS-UHFFFAOYSA-N 0.000 claims description 3
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 claims description 3
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 claims description 3
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 claims description 3
- 229940113120 dipropylene glycol Drugs 0.000 claims description 3
- 235000010382 gamma-tocopherol Nutrition 0.000 claims description 3
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 3
- 150000004667 medium chain fatty acids Chemical class 0.000 claims description 3
- XVTQAXXMUNXFMU-UHFFFAOYSA-N methyl 2-(3-oxo-2-pyridin-2-yl-1h-pyrazol-5-yl)acetate Chemical compound N1C(CC(=O)OC)=CC(=O)N1C1=CC=CC=N1 XVTQAXXMUNXFMU-UHFFFAOYSA-N 0.000 claims description 3
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 claims description 3
- 229950000688 phenothiazine Drugs 0.000 claims description 3
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 3
- 239000001069 triethyl citrate Substances 0.000 claims description 3
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 3
- 235000013769 triethyl citrate Nutrition 0.000 claims description 3
- JLGLQAWTXXGVEM-UHFFFAOYSA-N triethylene glycol monomethyl ether Chemical compound COCCOCCOCCO JLGLQAWTXXGVEM-UHFFFAOYSA-N 0.000 claims description 3
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 claims description 3
- 239000002478 γ-tocopherol Substances 0.000 claims description 3
- QUEDXNHFTDJVIY-DQCZWYHMSA-N γ-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-DQCZWYHMSA-N 0.000 claims description 3
- SNAQINZKMQFYFV-UHFFFAOYSA-N 1-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]butane Chemical compound CCCCOCCOCCOCCOC SNAQINZKMQFYFV-UHFFFAOYSA-N 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 230000000911 decarboxylating effect Effects 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 230000000379 polymerizing effect Effects 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 239000011627 DL-alpha-tocopherol Substances 0.000 description 4
- 235000001815 DL-alpha-tocopherol Nutrition 0.000 description 4
- 238000006000 Knoevenagel condensation reaction Methods 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 150000005846 sugar alcohols Polymers 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- YOMSJEATGXXYPX-UHFFFAOYSA-N 2-methoxy-4-vinylphenol Chemical compound COC1=CC(C=C)=CC=C1O YOMSJEATGXXYPX-UHFFFAOYSA-N 0.000 description 2
- HXDOZKJGKXYMEW-UHFFFAOYSA-N 4-ethylphenol Chemical compound CCC1=CC=C(O)C=C1 HXDOZKJGKXYMEW-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 238000007239 Wittig reaction Methods 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 229920001002 functional polymer Polymers 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000000622 liquid--liquid extraction Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000000638 solvent extraction Methods 0.000 description 2
- JAMNSIXSLVPNLC-UHFFFAOYSA-N (4-ethenylphenyl) acetate Chemical compound CC(=O)OC1=CC=C(C=C)C=C1 JAMNSIXSLVPNLC-UHFFFAOYSA-N 0.000 description 1
- VXQBJTKSVGFQOL-UHFFFAOYSA-N 2-(2-butoxyethoxy)ethyl acetate Chemical compound CCCCOCCOCCOC(C)=O VXQBJTKSVGFQOL-UHFFFAOYSA-N 0.000 description 1
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 1
- XLLXMBCBJGATSP-UHFFFAOYSA-N 2-phenylethenol Chemical class OC=CC1=CC=CC=C1 XLLXMBCBJGATSP-UHFFFAOYSA-N 0.000 description 1
- NGBBWVMJRDMNDN-UHFFFAOYSA-N 4-ethenyl-2,3-dimethoxyphenol Chemical compound COC1=C(O)C=CC(C=C)=C1OC NGBBWVMJRDMNDN-UHFFFAOYSA-N 0.000 description 1
- LHUWFIJCDKAODB-UHFFFAOYSA-N 4-ethenyl-3,5-dimethoxyphenol Chemical compound COC1=CC(O)=CC(OC)=C1C=C LHUWFIJCDKAODB-UHFFFAOYSA-N 0.000 description 1
- UMDJLUGAMDTLDI-UHFFFAOYSA-N 4-ethenyl-3-methoxyphenol Chemical compound COC1=CC(O)=CC=C1C=C UMDJLUGAMDTLDI-UHFFFAOYSA-N 0.000 description 1
- BHIANVQFGSWJKQ-UHFFFAOYSA-N C(=C)C1=C(C(=C(C=C1OC)O)OC)OC Chemical compound C(=C)C1=C(C(=C(C=C1OC)O)OC)OC BHIANVQFGSWJKQ-UHFFFAOYSA-N 0.000 description 1
- XGPNTVOFASLFOP-UHFFFAOYSA-N COC1=C(C(=C(C(=C1)C=C)OC)OC)O Chemical compound COC1=C(C(=C(C(=C1)C=C)OC)OC)O XGPNTVOFASLFOP-UHFFFAOYSA-N 0.000 description 1
- FVNSMMLTACMJBY-UHFFFAOYSA-N COC1=C(C(=C(C(=C1OC)O)OC)OC)C=C Chemical compound COC1=C(C(=C(C(=C1OC)O)OC)OC)C=C FVNSMMLTACMJBY-UHFFFAOYSA-N 0.000 description 1
- PLCQSPNGYRMMMP-UHFFFAOYSA-N COC1=C(C=C(C(=C1)C=C)OC)O Chemical compound COC1=C(C=C(C(=C1)C=C)OC)O PLCQSPNGYRMMMP-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- NGSWKAQJJWESNS-UHFFFAOYSA-N cis-para-coumaric acid Natural products OC(=O)C=CC1=CC=C(O)C=C1 NGSWKAQJJWESNS-UHFFFAOYSA-N 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- IXPUJMULXNNEHS-UHFFFAOYSA-L copper;n,n-dibutylcarbamodithioate Chemical compound [Cu+2].CCCCN(C([S-])=S)CCCC.CCCCN(C([S-])=S)CCCC IXPUJMULXNNEHS-UHFFFAOYSA-L 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229940071125 manganese acetate Drugs 0.000 description 1
- UOGMEBQRZBEZQT-UHFFFAOYSA-L manganese(2+);diacetate Chemical compound [Mn+2].CC([O-])=O.CC([O-])=O UOGMEBQRZBEZQT-UHFFFAOYSA-L 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- JESXATFQYMPTNL-UHFFFAOYSA-N mono-hydroxyphenyl-ethylene Natural products OC1=CC=CC=C1C=C JESXATFQYMPTNL-UHFFFAOYSA-N 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 150000002832 nitroso derivatives Chemical class 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 229960005323 phenoxyethanol Drugs 0.000 description 1
- 229940057847 polyethylene glycol 600 Drugs 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- KCDXJAYRVLXPFO-UHFFFAOYSA-N syringaldehyde Chemical compound COC1=CC(C=O)=CC(OC)=C1O KCDXJAYRVLXPFO-UHFFFAOYSA-N 0.000 description 1
- COBXDAOIDYGHGK-UHFFFAOYSA-N syringaldehyde Natural products COC1=CC=C(C=O)C(OC)=C1O COBXDAOIDYGHGK-UHFFFAOYSA-N 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 235000019149 tocopherols Nutrition 0.000 description 1
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
本発明は、４−ヒドロキシスチレン化合物の分離方法に関し、さらには、４−ヒドロキシベンズアルデヒド化合物をマロン酸と反応させ、ついで難揮発性溶媒と不揮発性溶媒と重合防止剤の存在下に薄膜蒸留することで、４−ヒドロキシスチレン化合物の難揮発性製剤を製造する方法に関する。 The present invention relates to a method for separating a 4-hydroxystyrene compound, and further, reacting a 4-hydroxybenzaldehyde compound with malonic acid, followed by thin-film distillation in the presence of a hardly volatile solvent, a non-volatile solvent, and a polymerization inhibitor. And relates to a method for producing a hardly volatile preparation of a 4-hydroxystyrene compound.
４−ヒドロキシスチレン化合物は、塗料や樹脂等の原料となる重合用モノマーとして知られており、近年では機能性ポリマーの原料として注目されている。食品分野においても、食品用香料として有用な化合物が知られており、例えば４−ヒドロキシスチレンは、甘いかび臭と肉のニュアンスを持った薬品的フェノール臭を有する香料化合物として知られている。また最近では、４−ビニルシリンゴール（３，５−ジメトキシ−４−ヒドロキシスチレン）が種々の薬理活性を有していることが知られ関心を集めている。 A 4-hydroxystyrene compound is known as a monomer for polymerization that is a raw material for paints, resins, and the like, and has recently attracted attention as a raw material for functional polymers. In the food field, compounds useful as food fragrances are known. For example, 4-hydroxystyrene is known as a fragrance compound having a chemical phenol odor with a sweet musty odor and meat nuance. Recently, 4-vinylsyringol (3,5-dimethoxy-4-hydroxystyrene) is known to have various pharmacological activities and has attracted attention.
４−ヒドロキシスチレンの合成方法としては、４−アセトキシスチレンの加水分解や４−エチルフェノールの脱水素、４−ヒドロキシベンズアルデヒドのＷｉｔｔｉｇ反応あるいはＫｎｏｅｖｅｎａｇｅｌ縮合およびそれに続く脱炭酸により得る方法等が知られている。これらの方法により合成した４−ヒドロキシスチレンの反応粗組成物は、未反応の原料および種々の副生成物の混合物となる。また、４−ヒドロキシスチレンは重合し易い化合物であるため、反応粗組成物には４−ヒドロキシスチレンの重合物も含まれ、それら不純物を除去するための分離・精製が必要となる。 Known methods for synthesizing 4-hydroxystyrene include hydrolysis of 4-acetoxystyrene, dehydrogenation of 4-ethylphenol, Wittig reaction of 4-hydroxybenzaldehyde or Knoevenagel condensation and subsequent decarboxylation. . The 4-hydroxystyrene reaction crude composition synthesized by these methods becomes a mixture of unreacted raw materials and various by-products. Further, since 4-hydroxystyrene is a compound that is easily polymerized, the reaction crude composition contains a polymer of 4-hydroxystyrene, and separation and purification are required to remove these impurities.
上記のような反応粗組成物から高純度の４−ヒドロキシスチレンを得る精製方法としては、再結晶により４−ヒドロキシスチレンを結晶として濾別する方法（特許文献１）や、向流液−液抽出を実施して４−ヒドロキシスチレンをトルエン溶液として得る方法（特許文献２）、多価アルコールの存在下に不純物を蒸留除去し、残留物として４−ヒドロキシスチレンの多価アルコール溶液を得る方法（特許文献３）が提案されている。 Examples of the purification method for obtaining high-purity 4-hydroxystyrene from the reaction crude composition as described above include a method of filtering 4-hydroxystyrene as crystals by recrystallization (Patent Document 1), and countercurrent liquid-liquid extraction. To obtain 4-hydroxystyrene as a toluene solution (Patent Document 2), a method of distilling off impurities in the presence of a polyhydric alcohol and obtaining a polyhydroxy alcohol solution of 4-hydroxystyrene as a residue (patent) Document 3) has been proposed.
しかしながら、結晶として濾別する方法においては、４−ヒドロキシスチレンの重合物や反応で生じた不揮発性成分の結晶への含有が懸念されるうえ、工業的スケールになると結晶乾燥工程における熱履歴が増大するため、乾燥時の分解や重合も懸念される。向流液−液抽出による方法においては、複雑な装置および設備と複雑な工程が必要という問題がある。また、蒸留の残留物として多価アルコール溶液で得る方法においては、結晶として得る時と同様に４−ヒドロキシスチレンの重合物や反応で生じた不揮発性成分が多価アルコール溶液へ含有されることが懸念される。したがって、本発明の課題は、４−ヒドロキシスチレンの重合物および反応によって生じた不揮発性成分を含有しない、高純度の４−ヒドロキシスチレンを得るための分離方法を提供することにある。 However, in the method of filtering as crystals, there is a concern about the inclusion of 4-hydroxystyrene polymer or non-volatile components generated by the reaction in the crystals, and the thermal history in the crystal drying process increases at an industrial scale. Therefore, there is a concern about decomposition and polymerization during drying. In the method by countercurrent liquid-liquid extraction, there is a problem that complicated apparatuses and equipment and complicated processes are required. Further, in the method of obtaining a polyhydric alcohol solution as a distillation residue, the polyhydric alcohol solution may contain a polymer of 4-hydroxystyrene and a non-volatile component produced by the reaction, as in the case of obtaining crystals. Concerned. Therefore, the subject of this invention is providing the isolation | separation method for obtaining 4-hydroxystyrene of high purity which does not contain the non-volatile component produced by the polymer of 4-hydroxystyrene and reaction.
上記課題を解決するために本発明者は鋭意検討を行った結果、４−ヒドロキシスチレン化合物を難揮発性溶媒および不揮発性溶媒の存在下に薄膜蒸留し留出させることで、高純度の４−ヒドロキシスチレン化合物を含む難揮発性溶媒の製剤が得られることを見出し、さらには薄膜蒸留の前後に重合防止剤を存在せしめることにより、経時的に４−ヒドロキシスチレン化合物の重合を防止できることも見い出し本発明を完成するに至った。 In order to solve the above-mentioned problems, the present inventor has intensively studied. As a result, the 4-hydroxystyrene compound is distilled in a thin film in the presence of a hardly volatile solvent and a non-volatile solvent to distill it. It has been found that a preparation of a hardly volatile solvent containing a hydroxystyrene compound can be obtained, and further, the polymerization of the 4-hydroxystyrene compound can be prevented over time by the presence of a polymerization inhibitor before and after thin film distillation. The invention has been completed.
すなわち、本発明は以下のとおりである。
１．下記式(1)で表される、４−ヒドロキシスチレン化合物を、難揮発性溶媒、不揮発性溶媒および重合防止剤の存在下に薄膜蒸留することを特徴とする、４−ヒドロキシスチレン化合物の分離方法。
２．難揮発性溶媒の１気圧での沸点が１８０〜３００℃であり、不揮発性溶媒の１２０℃の温度下における蒸気圧が１０Ｐａ未満であることを特徴とする前記分離方法。
３．難揮発性溶媒が、プロピレングリコール、３−メトキシ−３−メチルブチルアセテート、ジメチルスルホキシド、デカリン、エチレングリコールモノブチルエーテルアセテート、ジエチレングリコールモノメチルエーテル、エチレングリコール、ジエチレングリコールモノエチルエーテル、１−メチル−２−ピロリドン、エチレングリコールジブチルエーテル、ベンジルアルコール、テトラリン、イソホロン、ジエチレングリコールモノエチルエーテルアセテート、１，３−ジメチル−２−イミダゾリジノン、ジプロピレングリコール、ジエチレングリコールモノブチルエーテル、ジエチレングリコールモノブチルエーテル、トリプロピレングリコールモノメチルエーテル、ジエチレングリコール、エチレングリコールモノフェニルエーテル、ジエチレングリコールモノブチルエーテルアセテート、ジエチレングリコールジアセテート、トリエチレングリコールモノメチルエーテル、ジエチレングリコールジブチルエーテル、トリエチレングリコールモノエチルエーテル、エチレングリコールベンジルエーテル、トリアセチン、トリエチレングリコールブチルメチルエーテル、テトラエチレングリコールジメチルエーテル、トリエチルシトレートからなる群から選ばれる１種または２種以上であり、不揮発性溶媒が、ポリエチレングリコールまたは中鎖脂肪酸トリグリセライドであることを特徴とする、前記分離方法。
４．重合防止剤が、ハイドロキノン、ハイドロキノンモノメチルエーテル、ジブチルヒドロキシアニソール、ジブチルヒドロキシトルエン、フェノチアジン、α−トコフェロール、γ−トコフェロールからなる群から選ばれる１種または２種以上であることを特徴とする、前記分離方法。
５．薄膜蒸留が１０〜３００Ｐａの圧力および６０〜１２０℃の温度で行われることを特徴とする、前記分離方法。
６．４−ヒドロキシスチレン化合物が４−ビニルフェノールまたは４−ビニルシリンゴールであることを特徴とする、前記分離方法。
７．下記式(2)で表される４−ヒドロキシベンズアルデヒド化合物とマロン酸を縮合させ、ついで脱炭酸させた４−ヒドロキシスチレン化合物の反応粗組成物に、難揮発性溶媒および不揮発性溶媒を加え、重合防止剤の存在下に薄膜蒸留することを特徴とする、４−ヒドロキシスチレン化合物の難揮発性溶媒製剤の製造方法。
８．純度９９．５％以上の４−ヒドロキシスチレン化合物およびα-トコフェロールを含有するトリアセチン製剤。
That is, the present invention is as follows.
1. A method for separating a 4-hydroxystyrene compound, characterized in that the 4-hydroxystyrene compound represented by the following formula (1) is subjected to thin-film distillation in the presence of a hardly volatile solvent, a nonvolatile solvent and a polymerization inhibitor. .
2. The said separation method characterized by the boiling point in 1 atmosphere of a hardly volatile solvent being 180-300 degreeC, and the vapor pressure in the temperature of 120 degreeC of a non-volatile solvent being less than 10 Pa.
3. The hardly volatile solvent is propylene glycol, 3-methoxy-3-methylbutyl acetate, dimethyl sulfoxide, decalin, ethylene glycol monobutyl ether acetate, diethylene glycol monomethyl ether, ethylene glycol, diethylene glycol monoethyl ether, 1-methyl-2-pyrrolidone, Ethylene glycol dibutyl ether, benzyl alcohol, tetralin, isophorone, diethylene glycol monoethyl ether acetate, 1,3-dimethyl-2-imidazolidinone, dipropylene glycol, diethylene glycol monobutyl ether, diethylene glycol monobutyl ether, tripropylene glycol monomethyl ether, diethylene glycol, Ethylene glycol monophenyl ether Diethylene glycol monobutyl ether acetate, diethylene glycol diacetate, triethylene glycol monomethyl ether, diethylene glycol dibutyl ether, triethylene glycol monoethyl ether, ethylene glycol benzyl ether, triacetin, triethylene glycol butyl methyl ether, tetraethylene glycol dimethyl ether, triethyl citrate One or more selected from the group, and the non-volatile solvent is polyethylene glycol or medium chain fatty acid triglyceride, the separation method.
4). The separation is characterized in that the polymerization inhibitor is one or more selected from the group consisting of hydroquinone, hydroquinone monomethyl ether, dibutylhydroxyanisole, dibutylhydroxytoluene, phenothiazine, α-tocopherol, and γ-tocopherol. Method.
5). The separation method as described above, wherein the thin film distillation is performed at a pressure of 10 to 300 Pa and a temperature of 60 to 120 ° C.
6. The separation method described above, wherein the 4-hydroxystyrene compound is 4-vinylphenol or 4-vinylsyringol.
7). A hardly volatile solvent and a non-volatile solvent are added to a reaction crude composition of 4-hydroxystyrene compound obtained by condensing a 4-hydroxybenzaldehyde compound represented by the following formula (2) and malonic acid and then decarboxylating, and polymerizing. A method for producing a hardly volatile solvent preparation of a 4-hydroxystyrene compound, which comprises performing thin film distillation in the presence of an inhibitor.
8). A triacetin preparation containing a 4-hydroxystyrene compound having a purity of 99.5% or more and α-tocopherol.
本発明によれば、簡便な方法で極めて純度の高い４−ヒドロキシスチレン化合物の分離をすることができ、経時的に安定な難揮発性溶媒製剤として得られるので、４−ヒドロキシスチレン化合物の種々の応用用途に供することができる。 According to the present invention, a highly pure 4-hydroxystyrene compound can be separated by a simple method and obtained as a hardly volatile solvent preparation that is stable over time. Can be used for applications.
以下に、本発明を実施の形態に即して詳細に説明する。
本発明の分離方法に供される４−ヒドロキシスチレン化合物は下記式(1)で表される化合物である。
具体的には、４−ヒドロキシスチレン、４−ヒドロキシ−２−メトキシスチレン、４−ヒドロキシ−３−メトキシスチレン、４−ヒドロキシ−２，３−ジメトキシスチレン、４−ヒドロキシ−２，５−ジメトキシスチレン、４−ヒドロキシ−２，６−ジメトキシスチレン、４−ヒドロキシ−３，５−ジメトキシスチレン、４−ヒドロキシ−２，３，５−トリメトキシスチレン、４−ヒドロキシ−２，３，６−トリメトキシスチレン、４−ヒドロキシ−２，３，５，６−テトラメトキシスチレンが例示され、中でも４−ヒドロキシスチレンおよび４−ヒドロキシ−３，５−ジメトキシスチレンの有用性が高い。これら４−ヒドロキシスチレン化合物は、例えば高分子原料としての４−ヒドロキシスチレン化合物モノマーなどとして利用されているが、これらモノマーは製造時あるいは保存時に一部重合していることが多く、純度の高い４−ヒドロキシスチレン化合物を得るのに有用である。
Hereinafter, the present invention will be described in detail according to embodiments.
The 4-hydroxystyrene compound used for the separation method of the present invention is a compound represented by the following formula (1).
Specifically, 4-hydroxystyrene, 4-hydroxy-2-methoxystyrene, 4-hydroxy-3-methoxystyrene, 4-hydroxy-2,3-dimethoxystyrene, 4-hydroxy-2,5-dimethoxystyrene, 4-hydroxy-2,6-dimethoxystyrene, 4-hydroxy-3,5-dimethoxystyrene, 4-hydroxy-2,3,5-trimethoxystyrene, 4-hydroxy-2,3,6-trimethoxystyrene, 4-hydroxy-2,3,5,6-tetramethoxystyrene is exemplified, and 4-hydroxystyrene and 4-hydroxy-3,5-dimethoxystyrene are particularly useful. These 4-hydroxystyrene compounds are used, for example, as 4-hydroxystyrene compound monomers as polymer raw materials. These monomers are often partially polymerized during production or storage, and have high purity. -Useful for obtaining hydroxystyrene compounds.
また、４−ヒドロキシスチレン化合物は、４−ヒドロキシベンズアルデヒド化合物からＫｎｏｅｖｅｎａｇｅｌ縮合あるいはＷｉｔｔｉｇ反応により容易に得ることができる。Ｋｎｏｅｖｅｎａｇｅｌ縮合に因るときは、対応する４−ヒドロキシベンズアルデヒド化合物に対し、塩基の存在下過剰量のマロン酸を加え、加熱撹拌することにより得ることができる。Ｋｎｏｅｖｅｎａｇｅｌ縮合による生成物は４−ヒドロキシ桂皮酸化合物であるが、この生成物は４位のヒドロキシ基の影響でさらに脱炭酸をおこし、４−ヒドロキシスチレン化合物を生成する。反応終了後は定法に従い、抽出、洗浄、抽出溶媒を留去して反応粗組生物が得られる。 The 4-hydroxystyrene compound can be easily obtained from the 4-hydroxybenzaldehyde compound by Knoevenagel condensation or Wittig reaction. When it depends on Knoevenagel condensation, it can be obtained by adding an excess amount of malonic acid in the presence of a base to the corresponding 4-hydroxybenzaldehyde compound and stirring with heating. The product of Knoevenagel condensation is a 4-hydroxycinnamic acid compound, but this product is further decarboxylated under the influence of the 4-position hydroxy group to produce a 4-hydroxystyrene compound. After completion of the reaction, a crude reaction product is obtained by extraction, washing, and distilling off the extraction solvent according to a conventional method.
本発明では、４−ヒドロキシスチレン化合物は薄膜蒸留に供される。
薄膜蒸留とは、ある一定の温度に加熱された面上に被蒸留物（前記蒸留残渣）を連続的に供給して均一な薄膜を形成させ、該被蒸留物をその面上にある間だけ加熱し、揮発性成分を蒸発させることにより揮発性成分と不揮発性成分を分離する蒸留方法である。
In the present invention, the 4-hydroxystyrene compound is subjected to thin film distillation.
Thin film distillation is a method in which a product to be distilled (the distillation residue) is continuously supplied onto a surface heated to a certain temperature to form a uniform thin film, and the product to be distilled is only on the surface. It is a distillation method in which a volatile component and a non-volatile component are separated by heating and evaporating the volatile component.
本発明において、圧力および温度条件は１０〜３００Ｐａ、６０〜１２０℃、好ましくは２０〜２５０Ｐａ、７０〜１１０℃で行われる。６０℃未満では４−ヒドロキシスチレン化合物の留出に時間がかかり、一方、１２０℃を超えると４−ヒドロキシスチレン化合物の重合反応が起きてしまう可能性がある。 In the present invention, the pressure and temperature conditions are 10 to 300 Pa, 60 to 120 ° C., preferably 20 to 250 Pa, and 70 to 110 ° C. If it is less than 60 ° C., it takes time to distill the 4-hydroxystyrene compound, while if it exceeds 120 ° C., the polymerization reaction of the 4-hydroxystyrene compound may occur.
本発明においては、蒸留助溶媒として、難揮発性溶媒および不揮発性溶媒を用いる。本発明で用いられる難揮発性溶媒とは、１気圧で沸点１８０〜３００℃を有する有機溶媒をいい、具体的には、プロピレングリコール、３−メトキシ−３−メチルブチルアセテート、ジメチルスルホキシド、デカリン、エチレングリコールモノブチルエーテルアセテート、ジエチレングリコールモノメチルエーテル、エチレングリコール、ジエチレングリコールモノエチルエーテル、１−メチル−２−ピロリドン、エチレングリコールジブチルエーテル、ベンジルアルコール、テトラリン、イソホロン、ジエチレングリコールモノエチルエーテルアセテート、１，３−ジメチル−２−イミダゾリジノン、ジプロピレングリコール、ジエチレングリコールモノブチルエーテル、ジエチレングリコールモノブチルエーテル、トリプロピレングリコールモノメチルエーテル、ジエチレングリコール、エチレングリコールモノフェニルエーテル、ジエチレングリコールモノブチルエーテルアセテート、ジエチレングリコールジアセテート、トリエチレングリコールモノメチルエーテル、ジエチレングリコールジブチルエーテル、トリエチレングリコールモノエチルエーテル、エチレングリコールベンジルエーテル、トリアセチン、トリエチレングリコールブチルメチルエーテル、テトラエチレングリコールジメチルエーテル、トリエチルシトレート等が挙げられ、好ましくはトリアセチンが用いられる。 In the present invention, a hardly volatile solvent and a non-volatile solvent are used as the distillation cosolvent. The hardly volatile solvent used in the present invention refers to an organic solvent having a boiling point of 180 to 300 ° C. at 1 atmosphere, specifically, propylene glycol, 3-methoxy-3-methylbutyl acetate, dimethyl sulfoxide, decalin, Ethylene glycol monobutyl ether acetate, diethylene glycol monomethyl ether, ethylene glycol, diethylene glycol monoethyl ether, 1-methyl-2-pyrrolidone, ethylene glycol dibutyl ether, benzyl alcohol, tetralin, isophorone, diethylene glycol monoethyl ether acetate, 1,3-dimethyl- 2-Imidazolidinone, dipropylene glycol, diethylene glycol monobutyl ether, diethylene glycol monobutyl ether, tripropylene glycol Monomethyl ether, diethylene glycol, ethylene glycol monophenyl ether, diethylene glycol monobutyl ether acetate, diethylene glycol diacetate, triethylene glycol monomethyl ether, diethylene glycol dibutyl ether, triethylene glycol monoethyl ether, ethylene glycol benzyl ether, triacetin, triethylene glycol butylmethyl Examples include ether, tetraethylene glycol dimethyl ether, and triethyl citrate. Triacetin is preferably used.
本発明において、難揮発性溶媒の使用量は、４−ヒドロキシスチレン化合物に対して０．５〜５００質量％で用いることが好ましく、より好ましくは０．５〜２００質量％で用いられる。 In the present invention, the amount of the hardly volatile solvent used is preferably 0.5 to 500% by mass, more preferably 0.5 to 200% by mass, based on the 4-hydroxystyrene compound.
本発明で用いられる不揮発性溶媒とは、１２０℃の温度下における蒸気圧が１０Ｐａ未満である有機溶媒をいい、具体的には、ポリエチレングリコール６００（平均分子量５７０〜６３０）、あるいはこれ以上の分子量を有するポリエチレングリコール類、または脂肪酸トリグリセライド（構成脂肪酸が炭素数６以上のもの）が挙げられ、好ましくは構成脂肪酸が炭素数６〜炭素数１２の中鎖脂肪酸トリグリセライド（ＭＣＴ）が用いられる。ＭＣＴは、デリオス（コグニスジャパン社）、ココナードＭＫ（花王社）の名称で市場から入手することができる。 The non-volatile solvent used in the present invention refers to an organic solvent having a vapor pressure of less than 10 Pa at a temperature of 120 ° C., specifically, polyethylene glycol 600 (average molecular weight 570 to 630) or a molecular weight higher than this. Or a fatty acid triglyceride (having a constituent fatty acid having 6 or more carbon atoms), preferably a medium-chain fatty acid triglyceride (MCT) having 6 to 12 carbon atoms. MCT can be obtained from the market under the names Derios (Cognis Japan) and Coconado MK (Kao).
本発明において、不揮発性溶媒の使用量は、４−ヒドロキシスチレン化合物に対して０．５〜５００質量％で用いることが好ましく、より好ましくは０．５〜２００質量％で用いられる。 In this invention, it is preferable to use the usage-amount of a non-volatile solvent at 0.5-500 mass% with respect to 4-hydroxystyrene compound, More preferably, it is used at 0.5-200 mass%.
本発明においては、薄膜蒸留の前後において、４−ヒドロキシスチレン化合物中に重合防止剤を含有させておくことが有用である。本発明に用いることができる重合防止剤としては、ハイドロキノン、ハイドロキノンモノメチルエーテル、ジブチルヒドロキシアニソール、ジブチルヒドロキシトルエン等のフェノール類、フェノチアジン、ジフェニルアミン等のアミン類、ジブチルジチオカルバミン酸銅、酢酸マンガン等の重金属塩、ニトロソ化合物、ニトロ化合物、テトラメチルピペリジノオキシル誘導体等のアミノキシル類、α−トコフェロール、γ−トコフェロール等のトコフェロール類等が挙げられる。フェノール系重合防止剤の場合は、薄膜蒸留前に４−ヒドロキシスチレン化合物に含有させておくと、４−ヒドロキシスチレン化合物とともに蒸留されるため、常に重合防止効果を発揮することになり、特に有用である。 In the present invention, it is useful to include a polymerization inhibitor in the 4-hydroxystyrene compound before and after thin film distillation. Examples of the polymerization inhibitor that can be used in the present invention include phenols such as hydroquinone, hydroquinone monomethyl ether, dibutylhydroxyanisole and dibutylhydroxytoluene, amines such as phenothiazine and diphenylamine, heavy metal salts such as copper dibutyldithiocarbamate and manganese acetate. , Nitroso compounds, nitro compounds, aminoxyls such as tetramethylpiperidinooxyl derivatives, and tocopherols such as α-tocopherol and γ-tocopherol. In the case of a phenol-based polymerization inhibitor, if it is contained in a 4-hydroxystyrene compound prior to thin-film distillation, it will be distilled together with the 4-hydroxystyrene compound, so that it will always exhibit a polymerization prevention effect and is particularly useful. is there.
次に実施例を示して本発明をさらに具体的に説明するが、本発明は、これらの実施例に限定されるものではない。 EXAMPLES Next, although an Example is shown and this invention is demonstrated further more concretely, this invention is not limited to these Examples.
［実施例１］
４−ヒドロキシベンズアルデヒド３６．６ｇ（０．３ｍｏｌ）、マロン酸６２．４（０．６ｍｏｌ）、１−メチル−２−ピロリドン１００ｇを混合し、ピペリジン２７ｇを加え加熱撹拌し、還流下３時間反応させた。冷却後ｄｌ−α−トコフェロール０．１ｇ、酢酸エチル３６０ｇを加えて抽出・洗浄後溶媒を減圧留去し、反応粗組成物２３ｇを得た。これにトリアセチン２．３ｇおよびＭＣＴ（中央化成社：MASESTER-E7000）２３ｇを加え、薄膜蒸留に付し、７０〜９０℃／６０Ｐａの留分３３ｇを得た。このものは４−ヒドロキシスチレンを４７．７％含有し、溶媒を除いた純度としては９９．６％相当であった。
[Example 1]
4-Hydroxybenzaldehyde 36.6 g (0.3 mol), malonic acid 62.4 (0.6 mol) and 1-methyl-2-pyrrolidone 100 g were mixed, and 27 g of piperidine was added and stirred under heating, and reacted under reflux for 3 hours. It was. After cooling, 0.1 g of dl-α-tocopherol and 360 g of ethyl acetate were added, and after extraction and washing, the solvent was distilled off under reduced pressure to obtain 23 g of a crude reaction composition. To this, 2.3 g of triacetin and 23 g of MCT (Chuo Kasei Co., Ltd .: MASESTER-E7000) were added and subjected to thin-film distillation to obtain 33 g of a 70 to 90 ° C./60 Pa fraction. This contained 47.7% of 4-hydroxystyrene, and its purity excluding the solvent was equivalent to 99.6%.
［実施例２］
シリンガアルデヒド４０ｋｇ、マロン酸４２．６ｋｇ、１−メチル−２−ピロリドン６４ｋｇを混合し、ピペリジン１８．４ｋｇを加え加熱撹拌し、還流下３時間反応させた。冷却後ｄｌ−α−トコフェロール０．５ｋｇ、酢酸エチル２４０ｋｇを加えて抽出・洗浄後溶媒を減圧留去し、反応粗組成物１５．３ｋｇを得た。これにトリアセチン１．３ｋｇおよびＭＣＴ（中央化成社：MASESTER-E7000）１．３ｋｇを加え、薄膜蒸留に付し、８０〜１００℃／５０Ｐａの留分１４ｋｇを得、これにｄｌ−α−トコフェロールを０．１４ｋｇ加え、本発明の４−ビニルシリンゴール製剤を得た。このものは４−ビニルシリンゴールを６７．５％含有し、溶媒とｄｌ−α−トコフェロールを除いた純度としては９９．５％相当であった。
[Example 2]
40 kg of syringaldehyde, 42.6 kg of malonic acid, and 64 kg of 1-methyl-2-pyrrolidone were mixed, 18.4 kg of piperidine was added, and the mixture was heated and stirred, and reacted under reflux for 3 hours. After cooling, 0.5 kg of dl-α-tocopherol and 240 kg of ethyl acetate were added, and after extraction and washing, the solvent was distilled off under reduced pressure to obtain 15.3 kg of a crude reaction composition. To this, 1.3 kg of triacetin and 1.3 kg of MCT (Chuo Kasei Co., Ltd .: MASESTER-E7000) are added, and subjected to thin film distillation to obtain a 14 kg fraction of 80-100 ° C./50 Pa, and dl-α-tocopherol is added thereto. 0.14-kg was added and the 4-vinyl syringol formulation of this invention was obtained. This contained 67.5% of 4-vinylsyringol, and its purity excluding the solvent and dl-α-tocopherol was equivalent to 99.5%.
本発明によれば、簡便な方法で極めて純度の高い４−ヒドロキシスチレン化合物を分離することができ、経時的に安定な難揮発性溶媒製剤として得ることができる。このような４−ヒドロキシスチレン化合物の製剤は、機能性高分子原料や香料素材、さらには医薬的用途など、種々の応用用途に供することができる。
According to the present invention, a highly pure 4-hydroxystyrene compound can be separated by a simple method, and can be obtained as a hardly volatile solvent preparation that is stable over time. Such preparations of 4-hydroxystyrene compounds can be used for various applications such as functional polymer raw materials, perfume materials, and pharmaceutical applications.
Claims (8)
A triacetin preparation containing a 4-hydroxystyrene compound having a purity of 99.5% or more and α-tocopherol.
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