US20020077367A1 - Process for producing 3-l-menthoxypropane-1,2-diol - Google Patents
Process for producing 3-l-menthoxypropane-1,2-diol Download PDFInfo
- Publication number
- US20020077367A1 US20020077367A1 US09/962,122 US96212201A US2002077367A1 US 20020077367 A1 US20020077367 A1 US 20020077367A1 US 96212201 A US96212201 A US 96212201A US 2002077367 A1 US2002077367 A1 US 2002077367A1
- Authority
- US
- United States
- Prior art keywords
- menthoxypropane
- epoxy
- represented
- menthoxypropan
- diol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- MDVYIGJINBYKOM-UHFFFAOYSA-N 3-[[5-Methyl-2-(1-methylethyl)cyclohexyl]oxy]-1,2-propanediol Chemical compound CC(C)C1CCC(C)CC1OCC(O)CO MDVYIGJINBYKOM-UHFFFAOYSA-N 0.000 title claims abstract description 57
- 238000000034 method Methods 0.000 title claims abstract description 50
- QSPXTBSJQJHAPF-UHFFFAOYSA-N 2-[(1-methyl-4-propan-2-ylcyclohexyl)oxymethyl]oxirane Chemical compound C1CC(C(C)C)CCC1(C)OCC1OC1 QSPXTBSJQJHAPF-UHFFFAOYSA-N 0.000 claims abstract description 48
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 claims abstract description 32
- 239000000126 substance Substances 0.000 claims abstract description 31
- 239000003960 organic solvent Substances 0.000 claims abstract description 29
- 239000002841 Lewis acid Substances 0.000 claims abstract description 24
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 24
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000003444 phase transfer catalyst Substances 0.000 claims abstract description 22
- 125000005843 halogen group Chemical group 0.000 claims abstract description 18
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract description 8
- IMVMIMWLBYHMBW-UHFFFAOYSA-N 1-chloro-3-(1-methyl-4-propan-2-ylcyclohexyl)oxypropan-2-ol Chemical compound CC(C)C1CCC(C)(OCC(O)CCl)CC1 IMVMIMWLBYHMBW-UHFFFAOYSA-N 0.000 claims description 20
- 239000002585 base Substances 0.000 claims description 19
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 15
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 12
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 10
- 229910015900 BF3 Inorganic materials 0.000 claims description 7
- 150000003242 quaternary ammonium salts Chemical group 0.000 claims description 7
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 claims description 7
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 5
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 5
- 239000011592 zinc chloride Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 235000005074 zinc chloride Nutrition 0.000 claims description 3
- 229940102001 zinc bromide Drugs 0.000 claims description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- 238000006243 chemical reaction Methods 0.000 description 31
- 230000000052 comparative effect Effects 0.000 description 22
- 0 *CC1CO1 Chemical compound *CC1CO1 0.000 description 16
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000006735 epoxidation reaction Methods 0.000 description 15
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
- 239000003054 catalyst Substances 0.000 description 13
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
- 239000000543 intermediate Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 238000007259 addition reaction Methods 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 230000002378 acidificating effect Effects 0.000 description 7
- 150000007513 acids Chemical class 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- IZZBZFTTXPTJDE-IBSWDFHHSA-N CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OCC1CO1 Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OCC1CO1 IZZBZFTTXPTJDE-IBSWDFHHSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- KXHPPCXNWTUNSB-UHFFFAOYSA-M benzyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC1=CC=CC=C1 KXHPPCXNWTUNSB-UHFFFAOYSA-M 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 230000035484 reaction time Effects 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 239000006071 cream Substances 0.000 description 5
- YCCXQARVHOPWFJ-UHFFFAOYSA-M magnesium;ethane;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C YCCXQARVHOPWFJ-UHFFFAOYSA-M 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- MDVYIGJINBYKOM-IBSWDFHHSA-N CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OCC(O)CO Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OCC(O)CO MDVYIGJINBYKOM-IBSWDFHHSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 239000002537 cosmetic Substances 0.000 description 4
- 239000004210 ether based solvent Substances 0.000 description 4
- 239000006210 lotion Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 4
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- 239000007818 Grignard reagent Substances 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- -1 allyl halide Chemical class 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 3
- 238000004880 explosion Methods 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 150000004795 grignard reagents Chemical class 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- DOWLDRNPBNFHRY-UHFFFAOYSA-N 1-methyl-4-propan-2-yl-1-prop-2-enoxycyclohexane Chemical compound CC(C)C1CCC(C)(OCC=C)CC1 DOWLDRNPBNFHRY-UHFFFAOYSA-N 0.000 description 2
- HXPKUOKFSVGGHB-UHFFFAOYSA-N 1-methyl-4-propan-2-yl-1-propoxycyclohexane Chemical class CCCOC1(C)CCC(C(C)C)CC1 HXPKUOKFSVGGHB-UHFFFAOYSA-N 0.000 description 2
- HXVNBWAKAOHACI-UHFFFAOYSA-N 2,4-dimethyl-3-pentanone Chemical compound CC(C)C(=O)C(C)C HXVNBWAKAOHACI-UHFFFAOYSA-N 0.000 description 2
- OIFAHDAXIUURLN-UHFFFAOYSA-N 2-(fluoromethyl)oxirane Chemical compound FCC1CO1 OIFAHDAXIUURLN-UHFFFAOYSA-N 0.000 description 2
- AGIBHMPYXXPGAX-UHFFFAOYSA-N 2-(iodomethyl)oxirane Chemical compound ICC1CO1 AGIBHMPYXXPGAX-UHFFFAOYSA-N 0.000 description 2
- QNYBOILAKBSWFG-UHFFFAOYSA-N 2-(phenylmethoxymethyl)oxirane Chemical compound C1OC1COCC1=CC=CC=C1 QNYBOILAKBSWFG-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- PYUZDZAASJRLCI-IBSWDFHHSA-N CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OCC(O)CCl Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OCC(O)CCl PYUZDZAASJRLCI-IBSWDFHHSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 150000007514 bases Chemical class 0.000 description 2
- 239000013040 bath agent Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000002826 coolant Substances 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- GYZLOYUZLJXAJU-UHFFFAOYSA-N diglycidyl ether Chemical compound C1OC1COCC1CO1 GYZLOYUZLJXAJU-UHFFFAOYSA-N 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 229940041616 menthol Drugs 0.000 description 2
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
- 230000009965 odorless effect Effects 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 150000001451 organic peroxides Chemical class 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- 150000002978 peroxides Chemical class 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000003507 refrigerant Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 150000003333 secondary alcohols Chemical class 0.000 description 2
- 239000002453 shampoo Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 229940034610 toothpaste Drugs 0.000 description 2
- 239000000606 toothpaste Substances 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- ACCZHIYJPBLERU-UHFFFAOYSA-N 1-(1-methyl-4-propan-2-ylcyclohexyl)oxy-3-phenylmethoxypropan-2-ol Chemical compound C1CC(C(C)C)CCC1(C)OCC(O)COCC1=CC=CC=C1 ACCZHIYJPBLERU-UHFFFAOYSA-N 0.000 description 1
- PYUZDZAASJRLCI-UHFFFAOYSA-N 1-chloro-3-(5-methyl-2-propan-2-ylcyclohexyl)oxypropan-2-ol Chemical compound CC(C)C1CCC(C)CC1OCC(O)CCl PYUZDZAASJRLCI-UHFFFAOYSA-N 0.000 description 1
- DLVRPVNJFWEIFV-UHFFFAOYSA-N 1-chloro-3-prop-2-enoxypropan-2-ol Chemical compound ClCC(O)COCC=C DLVRPVNJFWEIFV-UHFFFAOYSA-N 0.000 description 1
- UQRRZVSYKCMJHC-UHFFFAOYSA-N 2-(1-methyl-4-propan-2-ylcyclohexyl)oxypropane-1,3-diol Chemical compound CC(C)C1CCC(C)(OC(CO)CO)CC1 UQRRZVSYKCMJHC-UHFFFAOYSA-N 0.000 description 1
- WLOHKZPZHBMVBK-UHFFFAOYSA-N 2-(chloromethyl)oxirane Chemical compound ClCC1CO1.ClCC1CO1 WLOHKZPZHBMVBK-UHFFFAOYSA-N 0.000 description 1
- IZZBZFTTXPTJDE-UHFFFAOYSA-N 2-[(5-methyl-2-propan-2-ylcyclohexyl)oxymethyl]oxirane Chemical compound CC(C)C1CCC(C)CC1OCC1OC1 IZZBZFTTXPTJDE-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- FARBQUXLIQOIDY-UHFFFAOYSA-M Dioctyldimethylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(C)CCCCCCCC FARBQUXLIQOIDY-UHFFFAOYSA-M 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000001166 anti-perspirative effect Effects 0.000 description 1
- 239000003213 antiperspirant Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- WOWHHFRSBJGXCM-UHFFFAOYSA-M cetyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)C WOWHHFRSBJGXCM-UHFFFAOYSA-M 0.000 description 1
- 239000007809 chemical reaction catalyst Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 239000008294 cold cream Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- RBNPOMFGQQGHHO-UHFFFAOYSA-N glyceric acid Chemical compound OCC(O)C(O)=O RBNPOMFGQQGHHO-UHFFFAOYSA-N 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 239000003676 hair preparation Substances 0.000 description 1
- 239000008266 hair spray Substances 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 239000005453 ketone based solvent Substances 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 229940051866 mouthwash Drugs 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 239000000133 nasal decongestant Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- PJGSXYOJTGTZAV-UHFFFAOYSA-N pinacolone Chemical compound CC(=O)C(C)(C)C PJGSXYOJTGTZAV-UHFFFAOYSA-N 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- UQFSVBXCNGCBBW-UHFFFAOYSA-M tetraethylammonium iodide Chemical compound [I-].CC[N+](CC)(CC)CC UQFSVBXCNGCBBW-UHFFFAOYSA-M 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/18—Ethers having an ether-oxygen atom bound to a carbon atom of a ring other than a six-membered aromatic ring
- C07C43/196—Ethers having an ether-oxygen atom bound to a carbon atom of a ring other than a six-membered aromatic ring containing hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/02—Preparation of ethers from oxiranes
- C07C41/03—Preparation of ethers from oxiranes by reaction of oxirane rings with hydroxy groups
Definitions
- the present invention relates to a process for producing 3-l-menthoxypropane-1,2-diol useful as a cooling agent and a refrigerant, and to a 3-l-menthoxypropane derivative useful as an intermediate for producing 3-l-menthoxypropane-1,2-diol and a process for producing the same.
- highly pure 3-l-menthoxypropane-1,2-diol and 3-l-menthoxypropane derivatives useful a synthetic intermediates for 3-l-menthoxypropane-1,2-diol can be obtained safely and in high yields through simple operations.
- 3-l-menthoxypropane-1,2-diol is a known compound as described in Japanese Patent Publication No. 48813/1986.
- 3-l-menthoxypropane-1,2-diol is excellent in safety and also have a nature of imparting a cooling effect on skin and mucous membrane like l-menthol. On the other hand, it is odorless unlike l-menthol, and itself has no smell. Therefore, in the case of using 3-l-menthoxypropane-1,2-diol, a cooling effect can be imparted to a product without affecting the fragrance imparted to the product.
- 3-l-menthoxypropane-1,2-diol has been blended with oral compositions such as tooth paste and chewing gum, and food and drink such as sherbet and hard candies, and further, it has been proposed to blend it with toilet articles such as cosmetics (Published Japanese Patent Application Nos. 25908/1985 and 208505/1988), an eye-pack agent (Published Japanese patent Application No. 96403/1987) and a hair cosmetic (Published Japanese Patent Application No. 192312/1987), and others such as an aerosol composition for anti-inflammatory agents (Published Japanese Patent Application No. 264522/1988).
- toilet articles such as cosmetics (Published Japanese Patent Application Nos. 25908/1985 and 208505/1988), an eye-pack agent (Published Japanese patent Application No. 96403/1987) and a hair cosmetic (Published Japanese Patent Application No. 192312/1987), and others such as an aerosol composition for anti-inflammatory agents (Published Japanese Patent Application No. 264522/1988).
- 1,2-epoxy-3-halogenopropane such as epichlorohydrin is known to be unstable and prone to decompose in the presence of an acid or a base [“Kagaku Daijiten”, p. 292, published by Tokyo Kagaku Dojin (1989)]. Therefore, in the case of this process where a 1,2-epoxy-3-halogenopropane is reacted in the presence of a base, the 1,2-epoxy-3-halogenopropane decomposes when the reaction takes a long period of time, so that it is difficult to synthesize 1,2-epoxy-3-l-menthoxypropane, and thus this process is not regarded as an advantageous process from industrial and economical viewpoints.
- the alcohol to be used in the process is a primary alcohol represented by the general formula:
- R represents a saturated or unsaturated linear or branched hydrocarbon group having 1 to 36 carbon atoms
- A represents an alkylene group having 2 to 4 carbon atoms
- p represents one number 0 to 100
- An object of the invention is to provide a process for producing highly pure 3-l-menthoxypropane-1,2-diol safely and in high yields through simple operations.
- Other objects of the invention is to provide an intermediate useful for obtaining highly pure 3-l-menthoxypropane-1,2-diol.
- Still other object of the invention is to provide a process for producing intermediates useful for obtaining 3-l-menthoxypropane-1,2-diol efficiently.
- a novel compound of a 1-halogeno-3-l-menthoxypropan-2-ol can be produced by adding l-menthol to a 1,2-epoxy-3-halogenopropane in an organic solvent in the presence of a Lewis acid.
- the invention relates to:
- the invention relates to:
- the invention relates to:
- the invention includes:
- phase transfer catalyst is a quaternary ammonium salt; as preferred embodiment.
- the invention relates to:
- the invention includes:
- l-menthol is added to a 1,2-epoxy-3-halogenopropane (I) in an organic solvent in the presence of a Lewis acid to produce a novel 1-halogeno-3-l-menthoxypropan-2-ol (II).
- the 1-halogeno-3-l-menthoxypropan-2-ol (II) is epoxidated with a base in the presence of a phase transfer catalyst to produce 1,2-epoxy-3-l-menthoxypropane (III), and 3-l-menthoxypropane-1,2-diol (IV) is obtained by hydrolyzing it.
- halogen atom X in the 1,2-epoxy-3-halogenopropane (I) fluorine atom, chlorine atom, bromine atom, iodine atom, and the like may be mentioned.
- specific examples of the 1,2-epoxy-3-halogenopropane include 1,2-epoxy-3-fluoropropane (epifluorohydrin), 1,2-epoxy-3-chloropropane (epichlorohydrin), 1,2-epoxy-3-bromopropane (epibromohydrin), 1,2-epoxy-3-iodopropane (epiiodohydrin), and the like.
- 1,2-epoxy-3-chloropropane epichlorohydrin
- 1,2-epoxy-3-chloropropane epibromohydrin
- the halogen atom X being chlorine atom or bromine atom
- 1,2-epoxy-3-chloropropane epichlorohydrin
- the molecular ratio of the 1,2-epoxy-3-halogenopropane (I) and 1-menthol to be used is preferably from about 0.8 to 2 mol, more preferably from 0.9 to 1.3 mol of 1-menthol relative to 1 mol of the 1,2-epoxy-3-halogenopropane (I).
- the amount of the Lewis acid to be used may be a similar amount to the amount of a catalyst in a conventional addition reaction, and is, in general, preferably from about 0.01 to 0.1 mol relative to 1 mol of the 1,2-epoxy-3-halogenopropane (I).
- Lewis acid examples include boron trifluoride ether complex, aluminum chloride, zinc chloride, zinc bromide, ferric chloride, and the like. One or two or more of them may be used. Among them, aluminum chloride and/or boron trifluoride ether complex are preferably used in view of good operability and economically low cost.
- organic solvent use is made of an organic solvent which does not affect adversely the addition of 1-menthol to a 1,2-epoxy-3-halogenopropane (I).
- organic solvent include aliphatic hydrocarbon solvents such as hexane, heptane and octane; alicyclic hydrocarbon solvents such as cyclohexane and methylcyclohexane; aromatic hydrocarbon solvents such as benzene, toluene and xylene; petroleum ether solvents, and the like.
- heptane and/or toluene are preferably used in view of good operability and economically low cost.
- the ratio of the organic solvent to be used to 1-menthol is preferably from about 0.5 to 5, more preferably about 1 to 3.
- the time for adding the solution of the 1,2-epoxy-3-halogenopropane (I) dissolved in an organic solvent is, in general, preferably about 0.5 to 10 hours, more preferably about 1.5 to 3 hours.
- the temperature for the addition reaction is preferably about 60 to 130° C., more preferably about 65 to 120° C.
- a 1-halogeno-3-1-menthoxypropan-2-ol (II) can be smoothly produced by the reaction for about 0.5 to 15 hours, preferably about 1 to 5 hours after completion of the addition of the organic solvent solution of a 1,2-epoxy-3-halogenopropane (I) with maintaining the above temperature.
- the 1-halogeno-3-1-menthoxypropan-2-ol (II) obtained by the above addition reaction is a novel compound hitherto unknown, and is stable, usually oily, and storable.
- the 1-halogeno-3-1-menthoxypropan-2-ol (II) obtained by the above addition reaction may be stored after purification by, for example, distillation or column chromatography or without any purification, and at the production of 1,2-epoxy-3-1-menthoxypropane or 3-1-menthoxypropane-1,2-diol (IV), the compound (II) may be taken out of a storing vessel and used.
- the 1-halogeno-3-1-menthoxypropan-2-ol (II) formed by the above addition reaction may be directly used for the next epoxidation reaction without additional-treatment such as purification, after cooling according to need.
- hydroxide, carbonate and/or an alkoxide of an alkali metal or alkaline earth metal may be used.
- specific examples thereof include lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, and the like.
- lithium hydroxide and/or potassium hydroxide are preferably used.
- the base is preferably added to the reaction system in the form of an aqueous solution.
- concentration of the aqueous solution of the base is preferably 40% or more, especially a high concentration of 45 to 55% because of the smooth proceeding of the epoxidation reaction.
- the amount of the base to be used is preferably from about 1.0 to 5.0 mol, particularly about 1.5 to 3.0 mol relative to 1 mol of the 1-halogeno-3-1-menthoxypropan-2-ol (II).
- a quaternary ammonium salt is suitably used, and specific examples thereof include industrially easily available quaternary ammonium salts such as tetramethylammonium chloride, tetrabutylammonium bromide, tetraethylammonium iodide, tetrabutylammonium iodide, trimethylhexadecylammonium chloride, dimethyldioctylammonium chloride, trimethylbenzylammonium chloride and trioctylmethylammonium chloride.
- tetramethylammonium chloride tetrabutylammonium bromide
- tetraethylammonium iodide tetrabutylammonium iodide
- trimethylhexadecylammonium chloride dimethyldioctylammonium chloride
- the amount of the phase transfer catalyst to be used is preferably from about 0.01 to 0.2 mol, particularly about 0.02 to 0.05 mol relative to 1 mol of the 1-halogeno-3-1-menthoxypropan-2-ol (II).
- the above epoxidation reaction is preferably carried out in an organic solvent.
- organic solvent there may be mentioned organic solvents which do not affect adversely the epoxidation reaction, for example, aliphatic hydrocarbon solvents such as hexane, heptane and octane; alicyclic hydrocarbon solvents such as cyclohexane and methylcyclohexane; aromatic hydrocarbon solvents such as benzene, toluene and xylene; ether solvents such as diethyl ether, diisopropyl ether, dimethoxyethane, tetrahydrofuran, dioxane and 1,3-dioxolane; petroleum ether solvents, and the like. One or two or more of them may be used. Among them, toluene and/or heptane are preferably used in view of smooth proceeding of the epoxidation reaction as well as good operability and economically low cost.
- the amount of the organic solvent to be used is preferably from about 1 to 10 parts by volume, particularly about 2 to 5 parts by volume relative to 1 part by volume of the 1-halogeno-3-1-menthoxypropan-2-ol (II).
- the above epoxidation reaction is preferably carried out under an atmosphere of an inert gas such as nitrogen gas or argon gas.
- the temperature for the epoxidation reaction is preferably about 40 to 100° C., particularly about 50 to 80° C.
- 1,2-Epoxy-3-1-menthoxypropane (III) can be smoothly produced by the reaction for about 0.5 to 6 hours, preferably about 1 to 4 hours with maintaining the above temperature.
- the 1,2-epoxy-3-1-menthoxypropane (III) obtained by the above epoxidation reaction is oily and storable. Therefore, the 1,2-epoxy-3-1-menthoxypropane (III) obtained by the above epoxidation reaction may be stored after purification by, for example, distillation or column chromatography or without any purification, and at the production of 3-1-menthoxypropane-1,2-diol (IV), the former compound may be taken out of a storing vessel and used.
- the 1,2-epoxy-3-1-menthoxypropane (III) obtained by the above epoxidation reaction may be directly used for the production of 3-1-menthoxypropane-1,2-diol (IV) without additional-treatment such as purification, after cooling according to need.
- 3-1-Menthoxypropane-1,2-diol (IV) is formed by hydrolyzing 1,2-epoxy-3-1-menthoxypropane (III) obtained by the above epoxidation reaction.
- the hydrolysis of 1,2-epoxy-3-1-menthoxypropane (III) is preferably carried out in the presence of an acidic catalyst.
- the acidic catalyst include mineral acids such as hydrochloric acid, sulfuric acid, nitric acid, perchloric acid and phosphoric acid; organic acids such as acetic acid, trifluoroacetic acid, trichloroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid and camphorsulfonic acid; and the like.
- sulfuric acid and/or perchloric acid are preferably used in view of smooth proceeding of the hydrolysis and economically low cost.
- the amount of the acidic catalyst to be used is preferably from about 0.02 to 0.2 equivalent, particularly about 0.05 to 0.15 equivalent relative to 1 mol of the 1,2-epoxy-3-1-menthoxypropane (III).
- the acidic catalyst is preferably added to the reaction system in the form of an aqueous solution.
- concentration of the aqueous solution of the acidic catalyst is preferably about 1 to 15%.
- the above hydrolysis is preferably carried out in an organic solvent.
- the organic solvent include ketone solvents such as acetone, methyl ethyl ketone, diethyl ketone, diisopropyl ketone, methyl tert-butyl ketone and cyclohexanone; ether solvents such as diisopropyl ether, dimethoxyethane, tetrahydrofuran, dioxane and 1,3-dioxolane; and the like. One or two or more of them may be used. Among them, acetone is preferably used in view of economically low cost.
- the amount of the organic solvent to be used is preferably from about 1 to 10 parts by volume, particularly about 2 to 5 parts by volume relative to 1 part by volume of 1,2-epoxy-3-l-menthoxypropane (III).
- the temperature for the above hydrolysis is preferably about 20 to 100° C., more preferably about 50 to 80° C.
- 3-l-menthoxypropane-1,2-diol (IV) can be produced by the reaction for about 0.5 to 5 hours, preferably about 1 to 3 hours with maintaining the above temperature. Isolation of 3-l-menthoxypropane-1,2-diol (IV) from the reaction product containing 3-l-menthoxypropane-1,2-diol (IV) can be carried out according to a conventional method.
- 3-l-menthoxypropane-1,2-diol (IV) can be isolated as a concentrate, for example, in the case that a water-soluble organic solvent is used in the reaction, by adding water to the reaction mixture according to need, removing the water-soluble organic solvent used in the reaction by evaporation, adding thereto an alkaline aqueous solution and a hydrocarbon organic solvent such as hexane, butane, benzene, toluene or xylene to neutralize the acidic catalyst used and to extract 3-l-menthoxypropane-1,2-diol (IV) with an organic solvent, and finally removing the solvent by evaporation.
- Purification of 3-l-menthoxypropane-1,2-diol (IV) can be effected by distillation or column chromatography.
- 3-l-menthoxypropane-1,2-diol (IV) obtained as above is used for a variety of applications such as cosmetics, toiletry goods, bath agents, food and drink, medicines, and the like with making good use of the characteristics such as cooling effect, refreshing effect, odorless property and safety.
- Examples thereof include various lotions such as body lotion, after-shave lotion and hair-growth lotion; skin cosmetics such as washing cream, vanishing cream, cleansing cream, cold cream, emulsion, toilet water, facial mask, makeup remover and lip cream; cataplasm, plaster, nasal decongestant, antiperspirant; hair-care goods such as shampoo, rinse, treatment and conditioner; hair cosmetics such as hair tonic, hair cream and hair spray; perfumes, colognes; bath agent, body shampoo, soap; shaving foam and gel; detergents, softeners; in-door aromatic agent; tooth paste; mouth wash; ointment; food and drink such as refreshing drink, gum, candy, ice cream, sherbet, jelly, tablet, troche; and the like.
- skin cosmetics such as washing cream, vanishing cream, cleansing cream, cold cream, emulsion, toilet water, facial mask, makeup remover and lip cream
- cataplasm, plaster nasal decongestant, antiperspirant
- hair-care goods such as shampoo, rinse, treatment and conditioner
- M-80 mass spectrometer manufacturing by Hitachi Ltd. (ionization voltage, 20 eV)
- IR (neat, cm ⁇ 1 ): 3422, 2955, 2922, 2869, 1456, 1385, 1370, 1344, 1180, 1114, 1067, 1050, 1011, 991, 974, 922, 845, 753.
- Example 7 As is apparent from the results shown in Table 2, in Example 7 wherein the reaction was carried out with using a phase transfer catalyst, at the reaction time of 4 hours, the conversion of 1-chloro-3-l-menthoxypropan-2-ol reached 100% and the selectivity to 1,2-epoxy-3-l-menthoxypropane is 98.2% which is an extremely high value.
- 3-l-menthoxypropane-1,2-diol useful as a cooling agent or a refrigerant can be produced safely and in high yields with a high purity through simple operations without using metal sodium, sodium hydride, a peroxide, or the like which is unstable and has an danger of explosion, and thus the process is industrially advantageous.
- a 1-halogeno-3-l-menthoxypropan-2-diol which is a novel intermediate for producing 3-l-menthoxypropane-1,2-diol can be produced through simple operations, safely and in high yields with a high purity by adding l-menthol to a 1,2-epoxy-3-halogenopropane in an organic solvent in the presence of a Lewis acid without using metal sodium, sodium hydride, a peroxide, or the like.
- 1,2-epoxy-3-l-menthoxypropane which is an intermediate for 3-l-menthoxypropane-1,2-diol can be produced safely and in high yields with a high purity through a simple operation of epoxidating the novel intermediate of a 1-halogeno-3-l-menthoxypropan-2-diol with a base in the presence of a phase transfer catalyst.
- novel 1-halogeno-3-l-menthoxypropan-2-diol of the invention is useful as an intermediate for producing 3-l-menthoxypropane-1,2-diol.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Epoxy Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
- The present invention relates to a process for producing 3-l-menthoxypropane-1,2-diol useful as a cooling agent and a refrigerant, and to a 3-l-menthoxypropane derivative useful as an intermediate for producing 3-l-menthoxypropane-1,2-diol and a process for producing the same. According to the invention, highly pure 3-l-menthoxypropane-1,2-diol and 3-l-menthoxypropane derivatives useful a synthetic intermediates for 3-l-menthoxypropane-1,2-diol can be obtained safely and in high yields through simple operations.
- 3-l-menthoxypropane-1,2-diol is a known compound as described in Japanese Patent Publication No. 48813/1986. 3-l-menthoxypropane-1,2-diol is excellent in safety and also have a nature of imparting a cooling effect on skin and mucous membrane like l-menthol. On the other hand, it is odorless unlike l-menthol, and itself has no smell. Therefore, in the case of using 3-l-menthoxypropane-1,2-diol, a cooling effect can be imparted to a product without affecting the fragrance imparted to the product. Thus, utilizing the above characteristic of 3-l-menthoxypropane-1,2-diol, 3-l-menthoxypropane-1,2-diol has been blended with oral compositions such as tooth paste and chewing gum, and food and drink such as sherbet and hard candies, and further, it has been proposed to blend it with toilet articles such as cosmetics (Published Japanese Patent Application Nos. 25908/1985 and 208505/1988), an eye-pack agent (Published Japanese patent Application No. 96403/1987) and a hair cosmetic (Published Japanese Patent Application No. 192312/1987), and others such as an aerosol composition for anti-inflammatory agents (Published Japanese Patent Application No. 264522/1988).
- Processes for producing 3-l-menthoxypropane-1,2-diol which are known heretofore included (i) a process wherein l-menthol is converted to the sodium salt with metal sodium or sodium hydride, then an allyl halide is reacted therewith to produce 3-l-menthoxypropan-1-ene, and it is oxidized using an organic peroxide to form a oxide, followed by hydrolysis (Japanese Patent Publication No. 48813/1986), and (ii) a process wherein l-menthol is added to benzyl glycidyl ether in the presence of a Lewis acid to produce 1-benzyloxy-3-l-menthoxypropan-2-ol and it is subjected to hydrogenolysis in the presence of palladium-carbon catalyst to eliminate the benzyl group (Published Japanese patent Application No. 82200/1995).
- However, in the above conventional method (i), sodium salt of l-menthol is produced with metal sodium or sodium hydride, and therefore there are problems of the risk of explosion and the generation of hydrogen gas. Furthermore, an intermediate of 3-l-menthoxypropan-1-ene is oxidized with an organic peroxide, and thus the risk of explosion also exists at the use. Accordingly, the process is not regarded as an industrially advantageous one and also some improvement is required from an economical point of view.
- Moreover, since the above conventional process (ii) is a process for the purpose of synthesizing an optical isomer, it is necessary to use expensive benzyl glycidyl ether. In addition, 3-l-menthoxypropane-1,2-diol finally obtained contains about 10% of 2-l-menthoxypropane-1,3-diol as a by-product, so that the purification or fractionation by silica gel column chromatography or the like is necessary and thus it is difficult to obtain a large amount of highly pure 3-l-menthoxypropane-1,2-diol.
- Furthermore, other than the above conventional processes, proposed is (iii) a process wherein l-menthol is added to a 1,2-epoxy-3-halogenopropane such as epichlorohydrin in an aqueous solution in the presence of a base and a quaternary ammonium salt to produce 1,2-epoxy-3-l-menthoxypropane which is a synthetic intermediate for 3-l-menthoxypropane-1,2-diol [French Patent No. 2479822 (1981)]. However, 1,2-epoxy-3-halogenopropane such as epichlorohydrin is known to be unstable and prone to decompose in the presence of an acid or a base [“Kagaku Daijiten”, p. 292, published by Tokyo Kagaku Dojin (1989)]. Therefore, in the case of this process where a 1,2-epoxy-3-halogenopropane is reacted in the presence of a base, the 1,2-epoxy-3-halogenopropane decomposes when the reaction takes a long period of time, so that it is difficult to synthesize 1,2-epoxy-3-l-menthoxypropane, and thus this process is not regarded as an advantageous process from industrial and economical viewpoints.
- Furthermore, as the reaction between epichlorohydrin and an alcohol, proposed is (iv) a process for producing 1-allyloxy-3-chloro-2-propanol by reacting epichlorohydrin with allyl alcohol in the presence of an acidic catalyst (Published Japanese patent Application No. 221/1990). In this conventional process (iv), however, the alcohol to be used in the reaction is only primary allyl alcohol and the application to a secondary alcohol, much less the addition reaction with menthol, is not reported.
- In addition, as another conventional process, there is proposed (v) a process wherein an epihalohydrin is reacted with an alcohol in the presence of an acid catalyst, then the product is treated with an alkali to form a glycidyl ether through ring closure, and after hydrolysis, the reaction mixture is heated at 100 to 230° C. in the presence of a salt formed from a strongly basic compound and a weekly acidic compound to produce a glycerol ether (Published Japanese Patent Application No. 212114/2000). However, in order to decompose an organohalogen contained in hydrolyzate of the glycidyl ether, this process requires heating the reaction mixture at a high temperature of 100 to 230° C., especially 150 to 200° C. in the presence of a salt formed from a strongly basic compound and a weekly acidic compound, and thus is not an efficient process. Furthermore, the alcohol to be used in the process is a primary alcohol represented by the general formula:
- R−(OA)p−OH
- (wherein R represents a saturated or unsaturated linear or branched hydrocarbon group having 1 to 36 carbon atoms, A represents an alkylene group having 2 to 4 carbon atoms, and p represents one number 0 to 100), and the use of secondary alcohol is not disclosed, much less the use of menthol is not disclosed at all.
- An object of the invention is to provide a process for producing highly pure 3-l-menthoxypropane-1,2-diol safely and in high yields through simple operations.
- Other objects of the invention is to provide an intermediate useful for obtaining highly pure 3-l-menthoxypropane-1,2-diol.
- Still other object of the invention is to provide a process for producing intermediates useful for obtaining 3-l-menthoxypropane-1,2-diol efficiently.
- The present inventors have extensively studied for achieving the above objects. As a result, a novel compound of a 1-halogeno-3-l-menthoxypropan-2-ol can be produced by adding l-menthol to a 1,2-epoxy-3-halogenopropane in an organic solvent in the presence of a Lewis acid. And, as a result of further studies, they have found that the novel 1-halogeno-3-l-menthoxypropan-2-ol is chemically stable and can be stored by itself, and 1,2-epoxy-3-l-menthoxypropane, which is also an intermediate for obtaining 3-l-mentoxypropane-1,2-diol, is obtained at a high reaction rate and in high yields by further epoxidating the 1-halogeno-3-l-menthoxypropan-2-ol with a base in the presence of a phase transfer catalyst, and objective 3-menthoxypropane-1,2-diol is obtained conveniently in good yields and at a high purity by hydrolyzing the 1,2-epoxy-3-l-menthoxypropane. Based on these finding, they have accomplished the invention.
- Namely, the invention relates to:
- (1) a process for producing 3-l-menthoxypropane1,2-diol, which comprises:
-
-
-
-
- and, the invention relates to:
- (2) a process for producing 3-l-menthoxypropane-1,2-diol, which comprises:
-
-
-
- Further, the invention relates to:
- (3) a process for producing a 1-halogeno-3-l-menthoxypropan-2-ol, which comprises:
-
-
- (wherein X represents a halogen atom).
- (4) a process for producing a 1,2-epoxy-3-l-menthoxypropane, which comprises:
-
-
- And, the invention includes:
- (5) the process as in any one of the above (1) to (4), wherein X is chlorine atom in the 1,2-epoxy-3-halogenopropane represented by the above general formula (I) and the 1-halogeno-3-l-menthoxypropan-2-ol represented by the above general formula (II);
- (6) the process as in the above (1) or (3), wherein the Lewis acid at least one selected from boron trifluoride ether complex, aluminum chloride; and
- (7) the process as in the above (1), (2), (4), (5) or (6), wherein the phase transfer catalyst is a quaternary ammonium salt; as preferred embodiment.
- Furthermore, the invention relates to:
-
- (wherein X represents a halogen atom).
- And, the invention includes:
-
- as a preferred embodiment.
- The following will explain the invention in detail.
-
- (wherein X represents a halogen atom)
- Namely, l-menthol is added to a 1,2-epoxy-3-halogenopropane (I) in an organic solvent in the presence of a Lewis acid to produce a novel 1-halogeno-3-l-menthoxypropan-2-ol (II). Then, the 1-halogeno-3-l-menthoxypropan-2-ol (II) is epoxidated with a base in the presence of a phase transfer catalyst to produce 1,2-epoxy-3-l-menthoxypropane (III), and 3-l-menthoxypropane-1,2-diol (IV) is obtained by hydrolyzing it.
- As a halogen atom X in the 1,2-epoxy-3-halogenopropane (I), fluorine atom, chlorine atom, bromine atom, iodine atom, and the like may be mentioned. Thus, specific examples of the 1,2-epoxy-3-halogenopropane include 1,2-epoxy-3-fluoropropane (epifluorohydrin), 1,2-epoxy-3-chloropropane (epichlorohydrin), 1,2-epoxy-3-bromopropane (epibromohydrin), 1,2-epoxy-3-iodopropane (epiiodohydrin), and the like. Among them, preferably used in the invention is 1,2-epoxy-3-chloropropane (epichlorohydrin) or 1,2-epoxy-3-chloropropane (epibromohydrin), the halogen atom X being chlorine atom or bromine atom, and more preferably used is 1,2-epoxy-3-chloropropane (epichlorohydrin).
- Commercially available 1,2-epoxy-3-halogenopropane (I) and l-menthol as they are can be used as starting materials.
- The addition of 1-menthol to a 1,2-epoxy-3-halogenopropane (I) is necessarily carried out in an organic solvent in the presence of a Lewis acid. When a brφnsted acid (protonic acid), a Grignard reagent or a base is used instead of a Lewis acid, an adduct (1-halogeno-3-1-menthoxypropane or 1,2-epoxy-3-1-menthoxypropane) is not formed or is formed only in low yields.
- At the addition of 1-menthol to a 1,2-epoxy-3-halogenopropane (I), preferably adopted is the method wherein a Lewis acid is added to a solution of 1-menthol dissolved in an organic solvent, and then, a solution of 1,2-epoxy-3-halogenopropane (I) dissolved in an organic solvent is added dropwise thereto to carry out the reaction.
- The molecular ratio of the 1,2-epoxy-3-halogenopropane (I) and 1-menthol to be used is preferably from about 0.8 to 2 mol, more preferably from 0.9 to 1.3 mol of 1-menthol relative to 1 mol of the 1,2-epoxy-3-halogenopropane (I).
- Moreover, the amount of the Lewis acid to be used may be a similar amount to the amount of a catalyst in a conventional addition reaction, and is, in general, preferably from about 0.01 to 0.1 mol relative to 1 mol of the 1,2-epoxy-3-halogenopropane (I).
- Specific examples of the Lewis acid include boron trifluoride ether complex, aluminum chloride, zinc chloride, zinc bromide, ferric chloride, and the like. One or two or more of them may be used. Among them, aluminum chloride and/or boron trifluoride ether complex are preferably used in view of good operability and economically low cost.
- As the organic solvent, use is made of an organic solvent which does not affect adversely the addition of 1-menthol to a 1,2-epoxy-3-halogenopropane (I). Specific examples thereof include aliphatic hydrocarbon solvents such as hexane, heptane and octane; alicyclic hydrocarbon solvents such as cyclohexane and methylcyclohexane; aromatic hydrocarbon solvents such as benzene, toluene and xylene; petroleum ether solvents, and the like. One or two or more of them may be used. Among them, heptane and/or toluene are preferably used in view of good operability and economically low cost.
- In general, the ratio of the organic solvent to be used to 1-menthol (volume/weight) is preferably from about 0.5 to 5, more preferably about 1 to 3.
- The addition of 1-menthol to a 1,2-epoxy-3-halogenopropane (I) is preferably carried out under an atmosphere of an inert gas such as nitrogen gas or argon gas for smooth proceeding of the addition reaction.
- Moreover, at carrying out the addition reaction by adding dropwise a solution of a 1,2-epoxy-3-halogenopropane (I) dissolved in an organic solvent to a solution of 1-menthol and a Lewis acid dissolved in an organic solvent, the time for adding the solution of the 1,2-epoxy-3-halogenopropane (I) dissolved in an organic solvent is, in general, preferably about 0.5 to 10 hours, more preferably about 1.5 to 3 hours.
- The temperature for the addition reaction is preferably about 60 to 130° C., more preferably about 65 to 120° C. A 1-halogeno-3-1-menthoxypropan-2-ol (II) can be smoothly produced by the reaction for about 0.5 to 15 hours, preferably about 1 to 5 hours after completion of the addition of the organic solvent solution of a 1,2-epoxy-3-halogenopropane (I) with maintaining the above temperature.
- The 1-halogeno-3-1-menthoxypropan-2-ol (II) obtained by the above addition reaction is a novel compound hitherto unknown, and is stable, usually oily, and storable.
- Therefore, the 1-halogeno-3-1-menthoxypropan-2-ol (II) obtained by the above addition reaction may be stored after purification by, for example, distillation or column chromatography or without any purification, and at the production of 1,2-epoxy-3-1-menthoxypropane or 3-1-menthoxypropane-1,2-diol (IV), the compound (II) may be taken out of a storing vessel and used. Alternatively, the 1-halogeno-3-1-menthoxypropan-2-ol (II) formed by the above addition reaction may be directly used for the next epoxidation reaction without additional-treatment such as purification, after cooling according to need.
- The 1-halogeno-3-1-menthoxypropan-2-ol (II) obtained by the above addition reaction is epoxydated with a base in the presence of a phase transfer catalyst to produce 1,2-epoxy-3-1-menthoxypropane (III).
- As the base to be used in the epoxidation reaction, hydroxide, carbonate and/or an alkoxide of an alkali metal or alkaline earth metal may be used. Specific examples thereof include lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, and the like. One or two or more of them may be used. Among them, sodium hydroxide and/or potassium hydroxide are preferably used.
- The base is preferably added to the reaction system in the form of an aqueous solution. The concentration of the aqueous solution of the base is preferably 40% or more, especially a high concentration of 45 to 55% because of the smooth proceeding of the epoxidation reaction.
- The amount of the base to be used is preferably from about 1.0 to 5.0 mol, particularly about 1.5 to 3.0 mol relative to 1 mol of the 1-halogeno-3-1-menthoxypropan-2-ol (II).
- As the phase transfer catalyst to be used in the above epoxidation reaction, a quaternary ammonium salt is suitably used, and specific examples thereof include industrially easily available quaternary ammonium salts such as tetramethylammonium chloride, tetrabutylammonium bromide, tetraethylammonium iodide, tetrabutylammonium iodide, trimethylhexadecylammonium chloride, dimethyldioctylammonium chloride, trimethylbenzylammonium chloride and trioctylmethylammonium chloride. One or two or more of them may be used. Among them, trimethylbenzylammonium chloride is preferably used in view of smooth proceeding of the epoxidation reaction and economically low cost.
- The amount of the phase transfer catalyst to be used is preferably from about 0.01 to 0.2 mol, particularly about 0.02 to 0.05 mol relative to 1 mol of the 1-halogeno-3-1-menthoxypropan-2-ol (II).
- The above epoxidation reaction is preferably carried out in an organic solvent. As the organic solvent, there may be mentioned organic solvents which do not affect adversely the epoxidation reaction, for example, aliphatic hydrocarbon solvents such as hexane, heptane and octane; alicyclic hydrocarbon solvents such as cyclohexane and methylcyclohexane; aromatic hydrocarbon solvents such as benzene, toluene and xylene; ether solvents such as diethyl ether, diisopropyl ether, dimethoxyethane, tetrahydrofuran, dioxane and 1,3-dioxolane; petroleum ether solvents, and the like. One or two or more of them may be used. Among them, toluene and/or heptane are preferably used in view of smooth proceeding of the epoxidation reaction as well as good operability and economically low cost.
- The amount of the organic solvent to be used is preferably from about 1 to 10 parts by volume, particularly about 2 to 5 parts by volume relative to 1 part by volume of the 1-halogeno-3-1-menthoxypropan-2-ol (II).
- The above epoxidation reaction is preferably carried out under an atmosphere of an inert gas such as nitrogen gas or argon gas.
- The temperature for the epoxidation reaction is preferably about 40 to 100° C., particularly about 50 to 80° C. 1,2-Epoxy-3-1-menthoxypropane (III) can be smoothly produced by the reaction for about 0.5 to 6 hours, preferably about 1 to 4 hours with maintaining the above temperature.
- The 1,2-epoxy-3-1-menthoxypropane (III) obtained by the above epoxidation reaction is oily and storable. Therefore, the 1,2-epoxy-3-1-menthoxypropane (III) obtained by the above epoxidation reaction may be stored after purification by, for example, distillation or column chromatography or without any purification, and at the production of 3-1-menthoxypropane-1,2-diol (IV), the former compound may be taken out of a storing vessel and used. Alternatively, the 1,2-epoxy-3-1-menthoxypropane (III) obtained by the above epoxidation reaction may be directly used for the production of 3-1-menthoxypropane-1,2-diol (IV) without additional-treatment such as purification, after cooling according to need.
- 3-1-Menthoxypropane-1,2-diol (IV) is formed by hydrolyzing 1,2-epoxy-3-1-menthoxypropane (III) obtained by the above epoxidation reaction.
- The hydrolysis of 1,2-epoxy-3-1-menthoxypropane (III) is preferably carried out in the presence of an acidic catalyst. Examples of the acidic catalyst include mineral acids such as hydrochloric acid, sulfuric acid, nitric acid, perchloric acid and phosphoric acid; organic acids such as acetic acid, trifluoroacetic acid, trichloroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid and camphorsulfonic acid; and the like. Among them, sulfuric acid and/or perchloric acid are preferably used in view of smooth proceeding of the hydrolysis and economically low cost.
- The amount of the acidic catalyst to be used is preferably from about 0.02 to 0.2 equivalent, particularly about 0.05 to 0.15 equivalent relative to 1 mol of the 1,2-epoxy-3-1-menthoxypropane (III).
- The acidic catalyst is preferably added to the reaction system in the form of an aqueous solution. The concentration of the aqueous solution of the acidic catalyst is preferably about 1 to 15%.
- The above hydrolysis is preferably carried out in an organic solvent. Examples of the organic solvent include ketone solvents such as acetone, methyl ethyl ketone, diethyl ketone, diisopropyl ketone, methyl tert-butyl ketone and cyclohexanone; ether solvents such as diisopropyl ether, dimethoxyethane, tetrahydrofuran, dioxane and 1,3-dioxolane; and the like. One or two or more of them may be used. Among them, acetone is preferably used in view of economically low cost.
- The amount of the organic solvent to be used is preferably from about 1 to 10 parts by volume, particularly about 2 to 5 parts by volume relative to 1 part by volume of 1,2-epoxy-3-l-menthoxypropane (III).
- The temperature for the above hydrolysis is preferably about 20 to 100° C., more preferably about 50 to 80° C. 3-l-menthoxypropane-1,2-diol (IV) can be produced by the reaction for about 0.5 to 5 hours, preferably about 1 to 3 hours with maintaining the above temperature. Isolation of 3-l-menthoxypropane-1,2-diol (IV) from the reaction product containing 3-l-menthoxypropane-1,2-diol (IV) can be carried out according to a conventional method. Although the method of recovery is not particularly limited, 3-l-menthoxypropane-1,2-diol (IV) can be isolated as a concentrate, for example, in the case that a water-soluble organic solvent is used in the reaction, by adding water to the reaction mixture according to need, removing the water-soluble organic solvent used in the reaction by evaporation, adding thereto an alkaline aqueous solution and a hydrocarbon organic solvent such as hexane, butane, benzene, toluene or xylene to neutralize the acidic catalyst used and to extract 3-l-menthoxypropane-1,2-diol (IV) with an organic solvent, and finally removing the solvent by evaporation. Purification of 3-l-menthoxypropane-1,2-diol (IV) can be effected by distillation or column chromatography.
- 3-l-menthoxypropane-1,2-diol (IV) obtained as above is used for a variety of applications such as cosmetics, toiletry goods, bath agents, food and drink, medicines, and the like with making good use of the characteristics such as cooling effect, refreshing effect, odorless property and safety. Examples thereof include various lotions such as body lotion, after-shave lotion and hair-growth lotion; skin cosmetics such as washing cream, vanishing cream, cleansing cream, cold cream, emulsion, toilet water, facial mask, makeup remover and lip cream; cataplasm, plaster, nasal decongestant, antiperspirant; hair-care goods such as shampoo, rinse, treatment and conditioner; hair cosmetics such as hair tonic, hair cream and hair spray; perfumes, colognes; bath agent, body shampoo, soap; shaving foam and gel; detergents, softeners; in-door aromatic agent; tooth paste; mouth wash; ointment; food and drink such as refreshing drink, gum, candy, ice cream, sherbet, jelly, tablet, troche; and the like.
- The following will explain the invention concretely with reference to Examples, but the invention is not limited at all by following Examples.
- By the way, in following Examples, the instruments used for measuring or analyzing physical properties are as follows.
- (1) Chemical purity
- Gas chromatograph: “HP6890” manufactured by HEWLETT PACKARD
- Column: “NEUTRABOND-1” manufactured by G L Science (inner diameter×length=0.25 mm×30 m)
- (2) Nuclear magnetic resonance spectrum:
-
- (3) Infrared absorption spectrum:
- Instrument: “Nicolet AVATAR 360” manufactured by Nicolet Japan K.K.
- Measuring method: NaCl film method
- (4) Mass spectrum (MS):
- M-80 mass spectrometer: manufacturing by Hitachi Ltd. (ionization voltage, 20 eV)
- (5) Polarimeter:
- “DIP-360” manufactured by Nihon Bunko K.K.
- (1) Under a nitrogen atmosphere, into a reaction flask (volume: 500 ml) were added l-menthol (manufactured by Takasago International Corporation) (136.7 g, 0.8763 mol) and n-heptane (295 ml), and the whole was dissolved at room temperature. Next, anhydrous aluminum chloride (3.5 g, 26.88 mmol) was added thereto and dissolved under stirring, and then the temperature was raised to 70° C. Into the solution was added dropwise epichlorohydrin (61 g, 0.6572 mol) at the same temperature over a period of 2 hours. After the addition, they were reacted at the same temperature for 7 hours. Thereafter, the reaction mixture was cooled to room temperature.
- (2) The reaction mixture obtained in the above (1) was washed with water and then washed with a 10% aqueous sodium carbonate solution, and removal of n-heptane by evaporation afforded an oily substance. The oily substance was distilled under reduced pressure to recover unreacted l-menthol (57.2 g, 0.37 mol) at a boiling point of 78 99° C./600 Pa (4.5 mmHg) and further to obtain 1-chloro-3-menthoxypropan-2-ol (117 g) (chemical purity: 97.8%) as a colorless oily substance (yield: 70% based on epichlorohydrin).
- (3) The analytical results of 1-chloro-3-l-menthoxypropan-2-ol obtained in the above (2) were as follows:
- [α]D 25:−73.7° (c=1.05, EtOH).
- MS (m/e,%): 248 (M+), 165, 163, 139, 138, 123, 109, 97, 95, 83, 81, 71, 69, 57, 55, 53, 43, 41, 29, 27.
- IR (neat, cm−1): 3422, 2955, 2922, 2869, 1456, 1385, 1370, 1344, 1180, 1114, 1067, 1050, 1011, 991, 974, 922, 845, 753.
-
- (1) As Examples 2 to 5, 1-chloro-3-l-menthoxypropan-2-ol was produced in a similar manner to Example 1 with the exception that each Lewis acid shown in following Table 1 was used in the same amount (26.88 mmol) as that in Example 1. The yields were all 65% or more as shown in Table 1.
- (2) On the other hand, 1-chloro-3-l-menthoxypropan-2-ol was produced in a similar manner to Example 1 with the exception that, as Comparative Examples 1 to 3, broφnsted acids (protonic acids) [sulfuric acid (H2SO4) (Comparative Example 1), phosphoric acid (85% H3PO4) (Comparative Example 2), and p-toluenesulfonic acid (monohydrate) (Comparative Example 3)]instead of the Lewis acid, and, as Comparative Example 4, a Grignard reagent (ethylmagnesium chloride: EtMgCl) instead of the Lewis acid were used in the same amount (26.88 mmol) as that in Example 1. The yields were as shown in Table 1.
- Under a nitrogen atmosphere, into a reaction flask (volume: 300 ml) were added l-menthol (10 g, 64.1 mmol) and toluene (50 ml), and the whole was dissolved at room temperature and then the inner temperature was lowered to 5°C. by ice-cooling. Thereafter, 60% sodium hydride (2.82 g, 70.5 mmol) was added thereto and then the temperature was raised to 100° C. Into the solution was added dropwise epichlorohydrin (5.93 g, 64.1 mmol) over a period of 1 hour. After the addition, they were reacted at the same temperature for 3 hours, but the adducts (1-chloro-3-l-menthoxypropan-2-ol or 1,2-epoxy-3-l-menthoxypropane) were not formed at all.
TABLE 1 Catalyst Yield Example 1 AlCl3 70.0% Example 2 ZnBr2 66.8% Example 3 FeCl3 67.6% Example 4 ZnCl2 72.5% Example 5 (C2H5)2O.BF3 65.7% Comparative Example 1 H2SO4 9.6% Comparative 85% H3PO4 14.8% Example 2 Comparative p-toluenesulfonic 4.0% Example 3 acid H2O Comparative EtMgCl 32.9% Example 4 Comparative note1) —2) Example 5 - As apparent from the results of Examples 1 to 5 shown in above Table 1, 1-chloro-3-l-menthoxypropan-2-ol was obtained in high yields of 65% or more by carrying out the reaction with Lewis acids [aluminum chloride (AlCl3), zinc bromide (ZnBr2), ferric chloride (FeCl3), zinc chloride (ZnCl2), boron trifluoride ether complex ((C2H5)2O·BF3)].
- On the other hand, as shown in the results of Comparative Examples 1 to 3, in the cases that brφnsted acids (protonic acids) [sulfonic acid (H2SO4) (Comparative Example 1), phosphoric acid (85% H3PO4) (Comparative Example 2), and p-toluenesulfonic acid (monohydrate) (Comparative Example 3)]were used as catalysts instead of the Lewis acid, 1-chloro-3-l-menthoxypropan-2-ol was formed but the yields were 9.6%, 14.8%, and 4.0%, respectively, which were lower than those in Examples 1 to 5.
- Moreover, as shown in the result of Comparative Example 4, in the case that a Grignard reagent [ethylmagnesium chloride (EtMgCl)]was used as the catalyst instead of the Lewis acids, 1-chloro-3-l-menthoxypropan-2-ol was formed but the yield was 32.9%, which was substantially lower that those in Examples 1 to 5.
- Furthermore, as is apparent from the result of Comparative Example 5, when the addition of l-menthol to epichlorohydrin was carried out using a base (sodium hydride), no adducts (1-chloro-3-l-menthoxypropan-2-ol or 1,2-epoxy-3-l-menthoxypropane) were formed.
- As is apparent from the above results, in the case of the process of the invention where the addition of l-menthol to epichlorohydrin was carried out in the presence of a Lewis acid, a novel compound of 1-chloro-3-l-menthoxypropan-2-ol can be obtained smoothly in high yields.
- (1) Under a nitrogen atmosphere, into a reaction flask (volume: 200 ml) were added 1-chloro-3-l-menthoxypropan-2-ol (50 g, chemical purity: 97.8%, 0.1968 mol) obtained in Example 1, toluene (75 ml), a 50% aqueous sodium hydroxide solution (31.49 g, 0.3936 mol) and a 50% aqueous benzyltrimethylammonium chloride solution (1.46 g, 4.26 mmol), and they were reacted at 75° C. for 2 hours. After completion of the reaction, the organic layer was washed with water and then the solvent (toluene) was removed to obtain an oily substance. The oily substance was distilled under reduced pressure to obtain 1,2-epoxy-3-l-menthoxypropane (34.6 g, chemical purity: 98.25%) [boiling point: 75-80° C./10.7 Pa (0.08 mmHg)]as a colorless transparent oily substance (yield: 97.0% based on 1-chloro-3-l-menthoxypropan-2-ol).
- (2) The analytical results of 1,2-epoxy-3-l-menthoxypropane obtained in the above (1) were as follows:
- [α]D 25: −90.95° (c=1.05, EtOH).
- MS (m/e, %): 212 (M+), 155, 138, 127, 123, 109, 95, 81, 71, 69, 67, 57, 55, 43, 31, 29, 27.
- IR (neat, cm−1): 3050, 2960, 2925, 2875, 1460, 1370, 1095, 910, 845, 765. 1H-NMR (CDCl3; δppm): 0.78 (3H, d, J=6.9), 0.81-0.88 (2H, m), 0.90 (3H, d, J=7.0), 0.92 (3H, d, J=6.6), 0.95-1.00 (1H, m), 1.24 (1H, m), 1.36 (1H, m) 1.59-1.67 (2H, m), 2.08 (1H, m), 2.14 (1H, m), 2.38 (1H, broad), 3.06-3.12 (1H, m), 3.38-3.44 (1H, m), 3.57-3.66 (2H, m), 3.71-3.75 (1H, dd), 3.90-3.96 (1H, m).
- (1) As Example 7, 1,2-epoxy-3-l-menthoxypropane was synthesized in a similar manner to Example 6 with using benzyltrimethylammonium chloride as the phase transfer catalyst and changing the reaction time. The conversion of 1-chloro-3-l-menthoxypropan-2-ol at each reaction time and the selectivity to 1,2-epoxy-3-l-menthoxypropane were as shown in following Table 2.
- (2) As Comparative Example 6, 1,2-epoxy-3-l-menthoxypropane was synthesized in a similar manner to Example 6 with the exception that a phase transfer catalyst (benzyltrimethylammonium chloride) was not added, with changing the reaction time. The conversion of 1-chloro-3-l-menthoxypropan-2-ol at each reaction time and the selectivity to 1,2-epoxy-3-l-menthoxypropane were as shown in following Table 2.
TABLE 2 Example 7 Comparative Example 6 (Phase transfer (Phase transfer Reaction catalyst) catalyst was not used) Time Conversion Selectivity Conversion Selectivity (hr) (%) (%) (%) (%) 2 98.2 98.8 86.3 98.2 3 99.7 98.5 90.5 97.1 4 100 98.2 93.0 97.1 5 — — 95.2 97.5 6 — — 96.8 97.3 7 — — 98.3 98.4 8 — — 99.1 97.4 9 — — 99.4 96.9 - As is apparent from the results shown in Table 2, in Example 7 wherein the reaction was carried out with using a phase transfer catalyst, at the reaction time of 4 hours, the conversion of 1-chloro-3-l-menthoxypropan-2-ol reached 100% and the selectivity to 1,2-epoxy-3-l-menthoxypropane is 98.2% which is an extremely high value.
- On the other hand, in Comparative Example 6 wherein the reaction was carried out without adding no phase transfer catalyst, increase of the conversion remarkably diminished after 2 hours of the reaction, and thus, at the reaction time of 9 hours, the conversion of 1-chloro-3-l-menthoxypropan-2-ol reached barely 99.4%. At that time, however, the selectivity to 1,2-epoxy-3-l-menthoxypropane decreased to 96.9%.
- From these results, it is evident that the process of the invention wherein epoxidation of 1-halogeno-3-l-menthoxypropan-2-ol to 1,2-epoxy-3-l-menthoxypropane is carried out with using a phase transfer catalyst is extremely effective.
- (1) Under a nitrogen atmosphere, into a reaction flask (volume: 3 liters) were added l-menthol (manufactured by Takasago International Corporation) (300 g, 1.923 mol) and toluene (616 ml), and the whole dissolved at room temperature. Then, anhydrous aluminum chloride (20.5 g, 0.154 mol) was added thereto and dissolved under stirring, and the temperature was raised to 116° C. Into the solution was added dropwise a solution of epichlorohydrin (178 g, 1.923 mol) dissolved in toluene (366 ml) over a period of 2 hours. After the addition, they were reacted at the same temperature for 1 hour. Thereafter, the reaction mixture was cooled to 50° C.
- (2) Under a nitrogen atmosphere, into the reaction mixture obtained in the above (1) were added a 50% aqueous sodium hydroxide solution (354 g, 3.846 mol) and a 50% aqueous benzyltrimethylammonium chloride solution (14.4 g), and they were reacted at 75° C. for 2 hours. After completion of the reaction, the mixture was washed with water (513 g) and then the solvent was removed by evaporation to obtain an oily substance. The substance was distilled under reduced pressure to obtain 1,2-epoxy-3-menthoxypropane (250g) [boiling point: 125-140° C./1200 Pa (9 mmHg)] as a colorless transparent oily substance (yield: 61.3% based on epichlorohydrin).
- (3) Under a nitrogen atmosphere, into a reaction flask (volume: 3 liters) were added 1,2-epoxy-3-l-menthoxypropan (245 g, 1.156 mol) obtained in the above (2), acetone (500 ml), and 3% aqueous sulfuric acid (235 g), and the whole was dissolved under stirring, followed by heating under reflux for 2 hours. Next, water (1000 ml) was added thereto and then, acetone was removed by evaporation under reduced pressure. Thereafter, a 3% aqueous sodium hydroxide solution (800 ml) and toluene (850 ml) was added thereto and after separation of the organic layer, the solvent was removed by evaporation to obtained an oily substance. The substance was distilled under reduced pressure to obtain 3-l-menthoxypropane-1,2-diol (250 g, chemical purity: 98.7%) [boiling point: 120-140° C./40 Pa (0.3 mmHg)] as a colorless transparent oily substance.
- According to the process of the invention, 3-l-menthoxypropane-1,2-diol useful as a cooling agent or a refrigerant can be produced safely and in high yields with a high purity through simple operations without using metal sodium, sodium hydride, a peroxide, or the like which is unstable and has an danger of explosion, and thus the process is industrially advantageous.
- Moreover, according to the invention, a 1-halogeno-3-l-menthoxypropan-2-diol which is a novel intermediate for producing 3-l-menthoxypropane-1,2-diol can be produced through simple operations, safely and in high yields with a high purity by adding l-menthol to a 1,2-epoxy-3-halogenopropane in an organic solvent in the presence of a Lewis acid without using metal sodium, sodium hydride, a peroxide, or the like.
- Furthermore, according to the invention, 1,2-epoxy-3-l-menthoxypropane which is an intermediate for 3-l-menthoxypropane-1,2-diol can be produced safely and in high yields with a high purity through a simple operation of epoxidating the novel intermediate of a 1-halogeno-3-l-menthoxypropan-2-diol with a base in the presence of a phase transfer catalyst.
- And, the novel 1-halogeno-3-l-menthoxypropan-2-diol of the invention is useful as an intermediate for producing 3-l-menthoxypropane-1,2-diol.
- While the invention has been described in detail and with reference to specific embodiments thereof, it will be apparent to one skilled in the art that various changed and modifications can be made therein without departing from the spirit and scope thereof.
- This application is based on Japanese patent application No. 2000-322287, filed Oct. 23, 2000, the entire contents thereof being hereby incorporated by reference.
Claims (11)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2000322287A JP4587549B2 (en) | 2000-10-23 | 2000-10-23 | 1-halogeno-3-l-menthoxypropan-2-ol |
JP2000-322287 | 2000-10-23 |
Publications (2)
Publication Number | Publication Date |
---|---|
US6407293B1 US6407293B1 (en) | 2002-06-18 |
US20020077367A1 true US20020077367A1 (en) | 2002-06-20 |
Family
ID=18800193
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/962,122 Expired - Lifetime US6407293B1 (en) | 2000-10-23 | 2001-09-26 | Process for producing 3-1-menthoxypropane-1,2-diol |
Country Status (8)
Country | Link |
---|---|
US (1) | US6407293B1 (en) |
EP (1) | EP1201635B1 (en) |
JP (1) | JP4587549B2 (en) |
KR (1) | KR100535698B1 (en) |
CN (1) | CN1166611C (en) |
CA (1) | CA2358617A1 (en) |
DE (1) | DE60105732T2 (en) |
ES (1) | ES2228723T3 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10392371B2 (en) | 2015-10-01 | 2019-08-27 | Senomyx, Inc. | Compounds useful as modulators of TRPM8 |
Families Citing this family (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4723751B2 (en) * | 2001-04-23 | 2011-07-13 | 高砂香料工業株式会社 | Process for producing 3-l-menthoxypropane-1,2-diol |
JP4179916B2 (en) * | 2003-04-16 | 2008-11-12 | 高砂香料工業株式会社 | Process for producing 2- (l-menthoxy) ethanol |
JP4953754B2 (en) * | 2006-10-19 | 2012-06-13 | 株式会社トクヤマ | Halohydrin compounds |
CN102249853A (en) * | 2010-05-19 | 2011-11-23 | 青岛科技大学 | Method for preparing neopentyl glycol |
MX348702B (en) * | 2011-09-01 | 2017-06-26 | Takasago Int Corp (Usa) | Novel substituted cyclohexane compounds. |
ES2659741T3 (en) | 2012-01-30 | 2018-03-19 | Symrise Ag | Preparations |
WO2013171018A2 (en) | 2012-05-16 | 2013-11-21 | Symrise Ag | Mixtures having improved cooling effect |
US10182584B2 (en) | 2012-12-12 | 2019-01-22 | Symrise Ag | Cooling preparations |
DE202012013357U1 (en) | 2012-12-12 | 2016-07-29 | Symrise Ag | preparations |
EP2801263B1 (en) | 2013-05-09 | 2021-04-14 | Symrise AG | Process for the preparation of a cooling composition in the form of granules |
EP2979751B1 (en) | 2014-07-29 | 2020-10-28 | Symrise AG | Process for the manufacturing of solid cooling agents |
CN104447227B (en) * | 2014-11-20 | 2016-03-30 | 昆山市亚香日用香料有限公司 | A kind of synthetic method of 3-L-menthoxypropane-1,2-glycol |
EP3059009B1 (en) | 2015-02-19 | 2022-05-04 | Symrise AG | Process for the storage of refreshing agents |
CN107548301B (en) | 2015-03-04 | 2021-05-11 | 西姆莱斯股份公司 | Composition containing menthol as soothing agent |
CN109310130B (en) | 2016-05-05 | 2022-05-17 | 西姆莱斯股份公司 | Cooling substance mixture |
WO2017198284A1 (en) | 2016-05-14 | 2017-11-23 | Symrise Ag | Menthol-containing aroma preparations |
KR102125662B1 (en) * | 2017-02-21 | 2020-06-22 | 히사미쓰 세이야꾸 가부시키가이샤 | Base agent for patch and patch using the same |
US11871772B2 (en) | 2018-08-10 | 2024-01-16 | Firmenich Incorporated | Antagonists of T2R54 and compositions and uses thereof |
EP3689324A1 (en) | 2019-02-04 | 2020-08-05 | Symrise AG | New cooling agents and preparations comprising them |
CN111543693A (en) * | 2020-04-10 | 2020-08-18 | 北京大学深圳研究生院 | High-efficient antibiotic gauze mask |
EP4259287A1 (en) | 2020-12-09 | 2023-10-18 | Symrise AG | A method for fighting microorganisms using menthol derivatives |
WO2022258189A1 (en) | 2021-06-10 | 2022-12-15 | Symrise Ag | Compositions for fighting malodors |
WO2023021012A1 (en) | 2021-08-16 | 2023-02-23 | Symrise Ag | Compositions |
WO2023083445A1 (en) | 2021-11-10 | 2023-05-19 | Symrise Ag | Compositions comprising trpm8 agonistic cooling agents |
WO2023147852A1 (en) | 2022-02-02 | 2023-08-10 | Symrise Ag | Compositions (iii) |
WO2023222213A1 (en) | 2022-05-18 | 2023-11-23 | Symrise Ag | Antimicrobial mixtures |
WO2022207944A2 (en) | 2022-07-11 | 2022-10-06 | Symrise Ag | Novel mixtures and uses of (2e)-3-(1,3-benzodioxol-5-yl)-n-phenyl-n-(tetrahydro-3-furanyl)-2-propenamide |
WO2024110023A1 (en) | 2022-11-23 | 2024-05-30 | Symrise Ag | An active composition comprising retinol |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE670419C (en) * | 1936-04-12 | 1939-01-18 | I G Farbenindustrie Akt Ges | Process for the production of halogen-containing oxalkyl ethers |
GB670419A (en) | 1946-08-21 | 1952-04-16 | Foxboro Co | Improvements in or relating to fluid-pressure servomotor control systems |
FR2479822A1 (en) | 1980-04-04 | 1981-10-09 | Fabre Sa Pierre | Aromatic, heterocyclic and aliphatic glycidyl ether(s) - intermediates for beta-blockers by reaction with primary amine(s) are prepd. by reacting epichlorohydrin with an appropriate alcohol |
JPS5888334A (en) * | 1981-11-20 | 1983-05-26 | Takasago Corp | 3-l-menthoxypropane-1,2-diol |
JPH06104654B2 (en) | 1987-11-10 | 1994-12-21 | ダイソー株式会社 | Optically active glycerol derivative |
GB9027448D0 (en) | 1990-12-18 | 1991-02-06 | Ciba Geigy Ag | Production of glycidyl compounds |
GB9125116D0 (en) | 1991-11-23 | 1992-01-22 | Ciba Geigy Ag | Chemical process |
JP2978043B2 (en) | 1993-09-16 | 1999-11-15 | 高砂香料工業株式会社 | (2S) -3-{(1R, 2S, 5R)-[5-methyl-2- (1-methylethyl) cyclohexyl] oxy} -1,2-propanediol, its production method and use |
JPH08119955A (en) * | 1994-10-26 | 1996-05-14 | Kyoeisha Chem Co Ltd | Epoxy-based reactive diluent |
JP3271904B2 (en) * | 1996-07-22 | 2002-04-08 | 花王株式会社 | Method for producing halohydrin ether and method for producing glycidyl ether |
JP3544134B2 (en) * | 1999-01-25 | 2004-07-21 | 花王株式会社 | Production method of glyceryl ether |
-
2000
- 2000-10-23 JP JP2000322287A patent/JP4587549B2/en not_active Expired - Fee Related
-
2001
- 2001-09-26 US US09/962,122 patent/US6407293B1/en not_active Expired - Lifetime
- 2001-10-09 DE DE60105732T patent/DE60105732T2/en not_active Expired - Lifetime
- 2001-10-09 ES ES01123353T patent/ES2228723T3/en not_active Expired - Lifetime
- 2001-10-09 EP EP01123353A patent/EP1201635B1/en not_active Expired - Lifetime
- 2001-10-11 CA CA002358617A patent/CA2358617A1/en not_active Abandoned
- 2001-10-23 KR KR10-2001-0065424A patent/KR100535698B1/en not_active IP Right Cessation
- 2001-10-23 CN CNB011358335A patent/CN1166611C/en not_active Expired - Fee Related
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10392371B2 (en) | 2015-10-01 | 2019-08-27 | Senomyx, Inc. | Compounds useful as modulators of TRPM8 |
Also Published As
Publication number | Publication date |
---|---|
CN1351002A (en) | 2002-05-29 |
KR20020031328A (en) | 2002-05-01 |
ES2228723T3 (en) | 2005-04-16 |
DE60105732T2 (en) | 2006-02-16 |
JP4587549B2 (en) | 2010-11-24 |
CA2358617A1 (en) | 2002-04-23 |
CN1166611C (en) | 2004-09-15 |
DE60105732D1 (en) | 2004-10-28 |
JP2002128720A (en) | 2002-05-09 |
US6407293B1 (en) | 2002-06-18 |
EP1201635B1 (en) | 2004-09-22 |
KR100535698B1 (en) | 2005-12-12 |
EP1201635A1 (en) | 2002-05-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6407293B1 (en) | Process for producing 3-1-menthoxypropane-1,2-diol | |
JP4723751B2 (en) | Process for producing 3-l-menthoxypropane-1,2-diol | |
JPS6324496B2 (en) | ||
Steyn et al. | Studies on cyclitols—XIII: Synthesis and stereochemistry of cyclopentanetriols and related epoxycyclanols | |
JPS621923B2 (en) | ||
US8993812B2 (en) | Method for preparing 2-methyl-4-phenylbutan-2-OL | |
Rozen et al. | Oxidative Cleavage of Methyl Ethers Using the HOF. cntdot. CH3CN Complex | |
JP5200071B2 (en) | Process for producing 3-l-menthoxypropane-1,2-diol | |
Segi et al. | Stereochemistry of Friedel-Crafts reaction of benzene with optically active 2-methyloxetane. | |
EP0771778B1 (en) | Process for producing all trans-form polyprenols | |
Cı́rkva et al. | Chemistry of [(perfluoroalkyl) methyl] oxiranes. Regioselectivity of ring opening with O-nucleophiles and the preparation of amphiphilic monomers | |
EP0326959B1 (en) | Perfume base composition comprising 2-cyclohexylpropanal and process for the preparation of this compound | |
CA1117021A (en) | Perfumery compositions with trimethyl-tetrahydropyran-2-ones | |
US4118426A (en) | Production of hydroxy ethers | |
ES2267408A1 (en) | Process for producing 2-(l-menthoxy)ethanol compound | |
JP6306017B2 (en) | Process for producing 2-methyl-4-phenylbutan-2-ol | |
Dobrev | A Convenient Synthesis of 2-Aminoalkyl Allyl Ethers | |
JPS59157289A (en) | Manufacture of cyclic terpene hydrocarbon | |
JPH0212458B2 (en) | ||
JPS5998030A (en) | Preparation of delta,epsilon-unsaturated carbonyl compound | |
JPS6048516B2 (en) | Cyclohexenyl-β-ketols, their preparation and use | |
JPH09124525A (en) | Production of 3,7,11,15,19,23,27-heptamethyl-6,10,14,18,22,26-octacosahexaen-1-ol |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: TAKASAGO INTERNATIONAL CORPORATION, JAPAN Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:AMANO, AKIRA;AKIYAMA, TERUYOSHI;MIURA, TAKASHI;AND OTHERS;REEL/FRAME:012210/0081 Effective date: 20010917 |
|
STCF | Information on status: patent grant |
Free format text: PATENTED CASE |
|
CC | Certificate of correction | ||
FPAY | Fee payment |
Year of fee payment: 4 |
|
FEPP | Fee payment procedure |
Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY |
|
FPAY | Fee payment |
Year of fee payment: 8 |
|
FPAY | Fee payment |
Year of fee payment: 12 |