JPH0572908B2 - - Google Patents
Info
- Publication number
- JPH0572908B2 JPH0572908B2 JP61234013A JP23401386A JPH0572908B2 JP H0572908 B2 JPH0572908 B2 JP H0572908B2 JP 61234013 A JP61234013 A JP 61234013A JP 23401386 A JP23401386 A JP 23401386A JP H0572908 B2 JPH0572908 B2 JP H0572908B2
- Authority
- JP
- Japan
- Prior art keywords
- dihydro
- benzofuran
- tetramethyl
- hydroxy
- group
- 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.)
- Expired - Lifetime
Links
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical class C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 claims description 29
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- -1 2-(3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)ethyl 3-(3,5-di-t- Butyl-4-hydroxyphenyl)propionate Chemical compound 0.000 description 60
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
- 239000000126 substance Substances 0.000 description 45
- 239000000243 solution Substances 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- 150000001875 compounds Chemical class 0.000 description 18
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 13
- 238000009835 boiling Methods 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 238000010898 silica gel chromatography Methods 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- 238000001819 mass spectrum Methods 0.000 description 10
- 238000000926 separation method Methods 0.000 description 10
- ODJQKYXPKWQWNK-UHFFFAOYSA-L 3-(2-carboxylatoethylsulfanyl)propanoate Chemical compound [O-]C(=O)CCSCCC([O-])=O ODJQKYXPKWQWNK-UHFFFAOYSA-L 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 230000003078 antioxidant effect Effects 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 239000007818 Grignard reagent Substances 0.000 description 8
- 150000004795 grignard reagents Chemical class 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000012267 brine Substances 0.000 description 7
- 238000007796 conventional method Methods 0.000 description 7
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 239000003963 antioxidant agent Substances 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- CUVSGNLPEWBVRP-UHFFFAOYSA-N 2-(2-hydroxyethyl)-2,4,6,7-tetramethyl-3h-1-benzofuran-5-ol Chemical compound CC1=C(O)C(C)=C2CC(C)(CCO)OC2=C1C CUVSGNLPEWBVRP-UHFFFAOYSA-N 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 5
- 235000006708 antioxidants Nutrition 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 230000000704 physical effect Effects 0.000 description 5
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical class C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 239000011261 inert gas Substances 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 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 description 4
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 3
- VJFYUVSMBZTZMK-UHFFFAOYSA-N 2-(hydroxymethyl)-2,4,6,7-tetramethyl-3h-1-benzofuran-5-ol Chemical compound CC1=C(O)C(C)=C2CC(C)(CO)OC2=C1C VJFYUVSMBZTZMK-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 229930003427 Vitamin E Natural products 0.000 description 3
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 3
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 3
- 150000002118 epoxides Chemical class 0.000 description 3
- VRZVPALEJCLXPR-UHFFFAOYSA-N ethyl 4-methylbenzenesulfonate Chemical compound CCOS(=O)(=O)C1=CC=C(C)C=C1 VRZVPALEJCLXPR-UHFFFAOYSA-N 0.000 description 3
- FMMOOAYVCKXGMF-MURFETPASA-N ethyl linoleate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OCC FMMOOAYVCKXGMF-MURFETPASA-N 0.000 description 3
- 229940031016 ethyl linoleate Drugs 0.000 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 description 3
- FMMOOAYVCKXGMF-UHFFFAOYSA-N linoleic acid ethyl ester Natural products CCCCCC=CCC=CCCCCCCCC(=O)OCC FMMOOAYVCKXGMF-UHFFFAOYSA-N 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- HJWLCRVIBGQPNF-UHFFFAOYSA-N prop-2-enylbenzene Chemical class C=CCC1=CC=CC=C1 HJWLCRVIBGQPNF-UHFFFAOYSA-N 0.000 description 3
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000011709 vitamin E Substances 0.000 description 3
- 235000019165 vitamin E Nutrition 0.000 description 3
- 229940046009 vitamin E Drugs 0.000 description 3
- YLWPNVNLSVXWFW-UHFFFAOYSA-N 2-(2-hydroxyethyl)-4,6,7-trimethyl-2,3-dihydro-1-benzofuran-5-ol Chemical compound CC1=C(O)C(C)=C2CC(CCO)OC2=C1C YLWPNVNLSVXWFW-UHFFFAOYSA-N 0.000 description 2
- JQMFQLVAJGZSQS-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide Chemical group C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)NC1=CC2=C(NC(O2)=O)C=C1 JQMFQLVAJGZSQS-UHFFFAOYSA-N 0.000 description 2
- ODJQKYXPKWQWNK-UHFFFAOYSA-N 3,3'-Thiobispropanoic acid Chemical compound OC(=O)CCSCCC(O)=O ODJQKYXPKWQWNK-UHFFFAOYSA-N 0.000 description 2
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 2
- WPMYUUITDBHVQZ-UHFFFAOYSA-N 3-(3,5-ditert-butyl-4-hydroxyphenyl)propanoic acid Chemical compound CC(C)(C)C1=CC(CCC(O)=O)=CC(C(C)(C)C)=C1O WPMYUUITDBHVQZ-UHFFFAOYSA-N 0.000 description 2
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- DFGKGUXTPFWHIX-UHFFFAOYSA-N 6-[2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]acetyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)C1=CC2=C(NC(O2)=O)C=C1 DFGKGUXTPFWHIX-UHFFFAOYSA-N 0.000 description 2
- LLQHSBBZNDXTIV-UHFFFAOYSA-N 6-[5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-4,5-dihydro-1,2-oxazol-3-yl]-3H-1,3-benzoxazol-2-one Chemical group C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC1CC(=NO1)C1=CC2=C(NC(O2)=O)C=C1 LLQHSBBZNDXTIV-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 229940087168 alpha tocopherol Drugs 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- 229940073608 benzyl chloride Drugs 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003518 caustics Substances 0.000 description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000011368 organic material Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical compound OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 229960000984 tocofersolan Drugs 0.000 description 2
- LDHQCZJRKDOVOX-UHFFFAOYSA-N trans-crotonic acid Natural products CC=CC(O)=O LDHQCZJRKDOVOX-UHFFFAOYSA-N 0.000 description 2
- 239000002076 α-tocopherol Substances 0.000 description 2
- 235000004835 α-tocopherol Nutrition 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
- UICWMBIWAMDELJ-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-2-yl acetate Chemical class C(C)(=O)OC1OC2=CC=CC=C2C1 UICWMBIWAMDELJ-UHFFFAOYSA-N 0.000 description 1
- HVIHEUQNVXCQBT-UHFFFAOYSA-N 2-(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)ethyl octadecanoate Chemical compound OC1=C(C)C(C)=C2OC(CCOC(=O)CCCCCCCCCCCCCCCCC)(C)CCC2=C1C HVIHEUQNVXCQBT-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-UHFFFAOYSA-N 0.000 description 1
- OHXAOPZTJOUYKM-UHFFFAOYSA-N 3-Chloro-2-methylpropene Chemical compound CC(=C)CCl OHXAOPZTJOUYKM-UHFFFAOYSA-N 0.000 description 1
- VKLOPQHLJNFYKK-UHFFFAOYSA-N 3-dodecylsulfanylpropanoic acid Chemical compound CCCCCCCCCCCCSCCC(O)=O VKLOPQHLJNFYKK-UHFFFAOYSA-N 0.000 description 1
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical group C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
- WTFUTSCZYYCBAY-SXBRIOAWSA-N 6-[(E)-C-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-N-hydroxycarbonimidoyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C/C(=N/O)/C1=CC2=C(NC(O2)=O)C=C1 WTFUTSCZYYCBAY-SXBRIOAWSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 238000006480 benzoylation reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- AEDZKIACDBYJLQ-UHFFFAOYSA-N ethane-1,2-diol;hydrate Chemical compound O.OCCO AEDZKIACDBYJLQ-UHFFFAOYSA-N 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 150000002680 magnesium Chemical class 0.000 description 1
- 125000002960 margaryl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 238000005667 methoxymethylation reaction Methods 0.000 description 1
- RWIKCBHOVNDESJ-NSCUHMNNSA-N methyl (e)-4-bromobut-2-enoate Chemical compound COC(=O)\C=C\CBr RWIKCBHOVNDESJ-NSCUHMNNSA-N 0.000 description 1
- IRIIKYHATWBASM-UHFFFAOYSA-N methyl 2-(5-hydroxy-4,6,7-trimethyl-2,3-dihydro-1-benzofuran-2-yl)acetate Chemical compound CC1=C(C)C(O)=C(C)C2=C1OC(CC(=O)OC)C2 IRIIKYHATWBASM-UHFFFAOYSA-N 0.000 description 1
- BBMCPEOFGAIHQK-UHFFFAOYSA-N methyl 4-bromo-3-methylbut-2-enoate Chemical compound COC(=O)C=C(C)CBr BBMCPEOFGAIHQK-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 238000005502 peroxidation Methods 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000006289 propionylation Effects 0.000 description 1
- 238000010515 propionylation reaction Methods 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 125000003696 stearoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Furan Compounds (AREA)
- Anti-Oxidant Or Stabilizer Compositions (AREA)
Description
〔産業上の利用分野〕
本発明は新規な2,3−ジヒドロベンゾフラン
誘導体に関する。
本発明によつて提供される2,3−ジヒドロベ
ンゾフラン誘導体は酸化防止作用を有しているか
又はその酸化防止作用を有する化合物の前駆体で
あり、酸化防止剤又はその合成中間体として有用
である。
〔従来の技術〕
従来、3,4−ジヒドロ−2H−ベンゾピラン
誘導体が酸化防止剤として有用なことは知られて
いる。例えば、ビタミンEは食品包装用プラスチ
ツクの酸化防止用の添加剤として用いられてお
り、また酸化防止作用を有する2−(3,4−ジ
ヒドロ−6−ヒドロキシ−2,5,7,8−テト
ラメチル−2H−1−ベンゾピラン−2−イル)
エチル ステアレート、2−(3,4−ジヒドロ
−6−ヒドロキシ−2,5,7,8−テトラメチ
ル−2H−1−ベンゾピラン−2−イル)エチル
3−(3,5−ジ−t−ブチル−4−ヒドロキ
シフエニル)プロピオネート、2−(3,4−ジ
ヒドロ−6−ヒドロキシ−2,5,7,8−テト
ラメチル−2H−1−ベンゾピラン−2−イル)
エチル 3−ドデシルチオプロピオネート、ジ
〔2−(3,4−ジヒドロ−6−ヒドロキシ−2,
5,7,8−テトラメチル−2H−1−ベンゾピ
ラン−2−イル)エチル〕 アジペート、ジ〔2
−(3,4−ジヒドロ−6−ヒドロキシ−2,5,
7,8−テトラメチル−2H−1−ベンゾピラン
−2−イル)エチル〕 3,3′−チオジプロピオ
ネートなどの種々の3,4−ジヒドロ−2H−ベ
ンゾピラン誘導体が提案されている(特開昭56−
145283号公報、特開昭57−146768号公報、特開昭
57−158776号公報、特開昭59−98078号公報及び
特開昭59−118781号公報参照)。
〔発明が解決しようとする問題点〕
ビタミンEは比較的高価であり、しかも容易に
酸化されて着色するため、酸化防止剤としての使
用範囲が制限されている。また上記の種々の3,
4−ジヒドロ−2H−ベンゾピラン誘導体はビタ
ミンEに比べると抗酸化性、着色性の面で改善さ
れているものの、酸化防止剤として必ずしも満足
できるものではない。
しかして、本発明の目的は、より高い酸化防止
活性を有し、少ない配合量で酸素感性な有機材料
の老化、着色などを防ぐことのできる新規な化合
物又はその化合物に容易に誘導される化合物を提
供するにある。
〔問題点を解決するための手段〕
本発明によれば、上記の目的は、一般式
[Industrial Field of Application] The present invention relates to novel 2,3-dihydrobenzofuran derivatives. The 2,3-dihydrobenzofuran derivative provided by the present invention has an antioxidant effect or is a precursor of a compound having an antioxidant effect, and is useful as an antioxidant or a synthetic intermediate thereof. . [Prior Art] It has been known that 3,4-dihydro-2H-benzopyran derivatives are useful as antioxidants. For example, vitamin E is used as an antioxidant additive in food packaging plastics, and 2-(3,4-dihydro-6-hydroxy-2,5,7,8-tetra methyl-2H-1-benzopyran-2-yl)
Ethyl stearate, 2-(3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)ethyl 3-(3,5-di-t- Butyl-4-hydroxyphenyl)propionate, 2-(3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)
Ethyl 3-dodecylthiopropionate, di[2-(3,4-dihydro-6-hydroxy-2,
5,7,8-tetramethyl-2H-1-benzopyran-2-yl)ethyl] adipate, di[2
-(3,4-dihydro-6-hydroxy-2,5,
Various 3,4-dihydro-2H-benzopyran derivatives such as 7,8-tetramethyl-2H-1-benzopyran-2-yl)ethyl]3,3'-thiodipropionate have been proposed (Unexamined Japanese Patent Publication No. 1982-
Publication No. 145283, Japanese Patent Application Publication No. 146768, Japanese Patent Application Publication No. 146768, Japanese Patent Publication No.
57-158776, JP-A-59-98078, and JP-A-59-118781). [Problems to be Solved by the Invention] Vitamin E is relatively expensive and is easily oxidized and colored, so its use as an antioxidant is limited. In addition, the above various 3,
Although 4-dihydro-2H-benzopyran derivatives have improved antioxidant properties and coloring properties compared to vitamin E, they are not necessarily satisfactory as antioxidants. Therefore, the object of the present invention is to provide a novel compound that has higher antioxidant activity and can prevent aging, discoloration, etc. of oxygen-sensitive organic materials with a small amount of compounding, or a compound that can be easily derived from the compound. is to provide. [Means for Solving the Problems] According to the present invention, the above object is achieved by solving the general formula
【化】
(式中、R1は水素原子又は低級アルキル基を
表わし、R2は水素原子又は式[Chemical formula] (In the formula, R 1 represents a hydrogen atom or a lower alkyl group, and R 2 represents a hydrogen atom or a
【式】で表わ
される基を示し、R3は水素原子又は水酸基の保
護基を表わし、nは1〜3の整数を表わす。R4
は置換基を有していてもよいアルキル基又は式A group represented by the formula: R 3 represents a hydrogen atom or a hydroxyl group-protecting group, and n represents an integer of 1 to 3. R4
is an optionally substituted alkyl group or formula
【化】
で表わされる基を示し、mは1〜4の整数を表わ
し、Aは硫黄原子を表わし、pは0又は1の整数
を表わす。)
で示される2,3−ジヒドロベンゾフラン誘導体
〔以下、これを2,3−ジヒドロベンゾフラン誘
導体()と記す〕を提供することによつて達成
される。
上記一般式()中、R1が表わす低級アルキ
ル基としてはメチル基、エチル基、プロピル基、
ブチル基などが挙げられるが、特にメチル基が好
ましい。R4が表わすアルキル基としてはメチル
基、エチル基、プロピル基、ブチル基、ペンチル
基、ヘキシル基、ヘプチル基、オクチル基、ノニ
ル基、デシル基、ペンタデシル基、ヘキサデシル
基、ヘプタデシル基などが挙げられ、またこれら
アルキル基が有してしてもよい置換基としてはオ
クチルチオ基、ドデシルチオ基、3,5−ジ−t
−ブチル−4−ヒドロキシフエニル基などが例示
される。式It represents a group represented by: m represents an integer of 1 to 4, A represents a sulfur atom, and p represents an integer of 0 or 1. ) [hereinafter referred to as 2,3-dihydrobenzofuran derivative ()]. In the above general formula (), the lower alkyl group represented by R 1 is a methyl group, an ethyl group, a propyl group,
Examples include butyl group, but methyl group is particularly preferred. Examples of the alkyl group represented by R 4 include methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, pentadecyl group, hexadecyl group, heptadecyl group, etc. , and substituents that these alkyl groups may have include octylthio group, dodecylthio group, 3,5-di-t
-Butyl-4-hydroxyphenyl group, etc. are exemplified. formula
【式】で表わされる基の代表例
としてアセチル基、ブチリル基、ステアロイル
基、3−(ドデシルチオ)プロピオニル基、3−
(3,5−ジ−t−ブチル−4−ヒドロキシフエ
ニル)プロピオニル基などが挙げられる。また
R3が表わす水酸基の保護基としては水酸基保護
の目的を達成する限り通常用いられるいずれの保
護基であつてもよく、例えばアセチル基、プロピ
オニル基、ブチリル基、ベンゾイル基などのアシ
ル基、メチル基、t−ブチル基、トリフエニルメ
チル基、ベンジル基、メトキシメチル基、1−エ
トキシエチル基、1−イソプトキシエチル基、ト
リメチルシリル基などが挙げられる。
2,3−ジヒドロベンゾフラン誘導体()の
代表例として次の化合物を挙げることができる。
(1) (2,3−ジヒドロ−5−ヒドロキシ−4,
6,7−トリメチル−1−ベンゾフラン−2−
イル)メタノールTypical examples of groups represented by the formula are acetyl group, butyryl group, stearoyl group, 3-(dodecylthio)propionyl group, 3-
Examples include (3,5-di-t-butyl-4-hydroxyphenyl)propionyl group. Also
The protecting group for the hydroxyl group represented by R 3 may be any commonly used protecting group as long as it achieves the purpose of protecting the hydroxyl group, such as an acyl group such as an acetyl group, a propionyl group, a butyryl group, or a benzoyl group, or a methyl group. , t-butyl group, triphenylmethyl group, benzyl group, methoxymethyl group, 1-ethoxyethyl group, 1-isoptoxyethyl group, trimethylsilyl group, and the like. The following compounds can be mentioned as representative examples of 2,3-dihydrobenzofuran derivatives (2). (1) (2,3-dihydro-5-hydroxy-4,
6,7-trimethyl-1-benzofuran-2-
methanol)
【化】
(2) (2,3−ジヒドロ−5−ヒドロキシ−2,
4,6,7−テトラメチル−1−ベンゾフラン
−2−イル)メタノール[Chem] (2) (2,3-dihydro-5-hydroxy-2,
4,6,7-tetramethyl-1-benzofuran-2-yl)methanol
【化】
(3) 2−(2,3−ジヒドロ−5−ヒドロキシ−
4,6,7−トリメチル−1−ベンゾフラン−
2−イル)エタノール[Chemical] (3) 2-(2,3-dihydro-5-hydroxy-
4,6,7-trimethyl-1-benzofuran-
2-yl)ethanol
【化】
(4) 2−(2,3−ジヒドロ−5−ヒドロキシ−
2,4,6,7−テトラメチル−1−ベンゾフ
ラン−2−イル)エタノール[Chemical] (4) 2-(2,3-dihydro-5-hydroxy-
2,4,6,7-tetramethyl-1-benzofuran-2-yl)ethanol
【化】
(5) 3−(2,3−ジヒドロ−5−ヒドロキシ−
4,6,7−トリメチル−1−ベンゾフラン−
2−イル)プロパノール[Chemical] (5) 3-(2,3-dihydro-5-hydroxy-
4,6,7-trimethyl-1-benzofuran-
2-yl)propanol
【化】
(6) 3−(2,3−ジヒドロ−5−ヒドロキシ−
2,4,6,7−テトラメチル−1−ベンゾフ
ラン−2−イル)プロパノール[Chemical] (6) 3-(2,3-dihydro-5-hydroxy-
2,4,6,7-tetramethyl-1-benzofuran-2-yl)propanol
【化】
(7) ジ〔(2,3−ジヒドロ−5−ヒドロキシ−
4,6,7−トリメチル−1−ベンゾフラン−
2−イル)メチル〕3,3′−チオジプロピオネ
ート[Chemical] (7) Di[(2,3-dihydro-5-hydroxy-
4,6,7-trimethyl-1-benzofuran-
2-yl)methyl]3,3'-thiodipropionate
【化】
(8) ジ〔(2,3−ジヒドロ−5−ヒドロキシ−
2,4,6,7−テトラメチル−1−ベンゾフ
ラン−2−イル)メチル〕3,3′−チオジプロ
ピオネート[Chemical] (8) Di[(2,3-dihydro-5-hydroxy-
2,4,6,7-tetramethyl-1-benzofuran-2-yl)methyl]3,3'-thiodipropionate
【化】
(9) ジ〔2−(2,3−ジヒドロ−5−ヒドロキ
シ−4,6,7−トリメチル−1−ベンゾフラ
ン−2−イル)エチル〕3,3′−チオジプロピ
オネート[Chemical formula] (9) Di[2-(2,3-dihydro-5-hydroxy-4,6,7-trimethyl-1-benzofuran-2-yl)ethyl]3,3'-thiodipropionate
【化】
(10) ジ〔2−(2,3−ジヒドロ−5−ヒドロキ
シ−2,4,6,7−テトラメチル−1−ベン
ゾフラン−2−イル)エチル〕3,3′−チオジ
プロピオネート[Chemical formula] (10) Di[2-(2,3-dihydro-5-hydroxy-2,4,6,7-tetramethyl-1-benzofuran-2-yl)ethyl]3,3'-thiodipropio Nate
【化】
(11) ジ〔3−(2,3−ジヒドロ−5−ヒドロキ
シ−4,6,7−トリメチル−1−ベンゾフラ
ン−2−イル)プロピル〕3,3′−チオジプロ
ピオネート[Chemical formula] (11) Di[3-(2,3-dihydro-5-hydroxy-4,6,7-trimethyl-1-benzofuran-2-yl)propyl]3,3'-thiodipropionate
【化】
(12) ジ〔3−(2,3−ジヒドロ−5−ヒドロキ
シ−2,4,6,7−テトラメチル−1−ベン
ゾフラン−2−イル)プロピル〕3,3′−チオ
ジプロピオネート[Chemical formula] (12) Di[3-(2,3-dihydro-5-hydroxy-2,4,6,7-tetramethyl-1-benzofuran-2-yl)propyl]3,3'-thiodipropio Nate
【化】
(13) ジ〔(2,3−ジヒドロ−5−ヒドロキシ−
2,4,6,7−テトラメチル−1−ベンゾフ
ラン−2−イル)メチル〕スクシネート[Chemical] (13) Di[(2,3-dihydro-5-hydroxy-
2,4,6,7-tetramethyl-1-benzofuran-2-yl)methyl]succinate
【化】
(14) ジ〔(2,3−ジヒドロ−5−ヒドロキシ−
2,4,6,7−テトラメチル−1−ベンゾフ
ラン−2−イル)エチル〕スクシネート[Chemical] (14) Di[(2,3-dihydro-5-hydroxy-
2,4,6,7-tetramethyl-1-benzofuran-2-yl)ethyl]succinate
【化】
(15) ジ〔(2,3−ジヒドロ−5−ヒドロキシ−
2,4,6,7−テトラメチル−1−ベンゾフ
ラン−2−イル)メチル〕アジペート[Chemical] (15) Di[(2,3-dihydro-5-hydroxy-
2,4,6,7-tetramethyl-1-benzofuran-2-yl)methyl]adipate
【化】
(16) ジ〔2−(2,3−ジヒドロ−5−ヒドロキ
シ−2,4,6,7−テトラメチル−1−ベン
ゾフラン−2−イル)エチル〕アジペート[Chemical formula] (16) Di[2-(2,3-dihydro-5-hydroxy-2,4,6,7-tetramethyl-1-benzofuran-2-yl)ethyl]adipate
【化】
(17) ジ〔(2,3−ジヒドロ−5−ヒドロキシ−
2,4,6,7−テトラメチル−1−ベンゾフ
ラン−2−イル)メチル〕セパケート[Chemical] (17) Di[(2,3-dihydro-5-hydroxy-
2,4,6,7-tetramethyl-1-benzofuran-2-yl)methyl]sepacate
【化】
(18) ジ〔2−(2,3−ジヒドロ−5−ヒドロキ
シ−2,4,6,7−テトラメチル−1−ベン
ゾフラン−2−イル)エチル〕セパケート[Chemical formula] (18) Di[2-(2,3-dihydro-5-hydroxy-2,4,6,7-tetramethyl-1-benzofuran-2-yl)ethyl]sepacate
【化】
(19) (2,3−ジヒドロ−5−ヒドロキシ−2,
4,6,7−テトラメチル−1−ベンゾフラン
−2−イル)メチル 3−(3,5−ジ−t−
ブチル−4−ヒドロキシフエニル)プロピオネ
ート[Chemical] (19) (2,3-dihydro-5-hydroxy-2,
4,6,7-tetramethyl-1-benzofuran-2-yl)methyl 3-(3,5-di-t-
Butyl-4-hydroxyphenyl)propionate
【化】
(20) 2−(2,3−ジヒドロ−5−ヒドロキシ−
2,4,6,7−テトラメチル−1−ベンゾフ
ラン−2−イル)エチル 3−(3,5−ジ−
t−ブチル−4−ヒドロキシフエニル)プロピ
オネート[Chemical] (20) 2-(2,3-dihydro-5-hydroxy-
2,4,6,7-tetramethyl-1-benzofuran-2-yl)ethyl 3-(3,5-di-
t-Butyl-4-hydroxyphenyl)propionate
【化】
(21) (2,3−ジヒドロ−5−ヒドロキシ−
2,4,6,7−テトラメチル−1−ベンゾフ
ラン−2−イル)メチル ステアレート[Chemical] (21) (2,3-dihydro-5-hydroxy-
2,4,6,7-tetramethyl-1-benzofuran-2-yl)methyl stearate
【化】
(22) 2−(2,3−ジヒドロ−5−ヒドロキシ
−2,4,6,7−テトラメチル−1−ベンゾ
フラン−2−イル)エチル ステアレート[Chemical formula] (22) 2-(2,3-dihydro-5-hydroxy-2,4,6,7-tetramethyl-1-benzofuran-2-yl)ethyl stearate
【化】
(23) (2,3−ジヒドロ−5−ヒドロキシ−
2,4,6,7−テトラメチル−1−ベンゾフ
ラン−2−イル)メチル 3−(ドデシルチオ)
プロピオネート[C] (23) (2,3-dihydro-5-hydroxy-
2,4,6,7-tetramethyl-1-benzofuran-2-yl)methyl 3-(dodecylthio)
Propionate
【化】
(24) 2−(2,3−ジヒドロ−5−ヒドロキシ
−2,4,6,7−テトラメチル−1−ベンゾ
フラン−2−イル)エチル 3−(ドデシルチ
オ)プロピオネート[Chemical formula] (24) 2-(2,3-dihydro-5-hydroxy-2,4,6,7-tetramethyl-1-benzofuran-2-yl)ethyl 3-(dodecylthio)propionate
【化】
(25) (2,3−ジヒドロ−5−ヒドロキシ−
2,4,6,7−テトラメチル−1−ベンゾフ
ラン−2−イル)メチル アセテート[C] (25) (2,3-dihydro-5-hydroxy-
2,4,6,7-tetramethyl-1-benzofuran-2-yl)methyl acetate
【化】
(26) (5−ベンジルオキシ−2,3−ジヒドロ
−2,4,6,7−テトラメチル−1−ベンゾ
フラン−2−イル)メタノール[Chemical formula] (26) (5-benzyloxy-2,3-dihydro-2,4,6,7-tetramethyl-1-benzofuran-2-yl)methanol
【化】
(27) 2−(5−ベンジルオキシ−2,3−ジヒ
ドロ−2,4,6,7−テトラメチル−1−ベ
ンゾフラン−2−イル)エタノール[Chemical formula] (27) 2-(5-benzyloxy-2,3-dihydro-2,4,6,7-tetramethyl-1-benzofuran-2-yl)ethanol
【化】
(28) 3−(5−ベンジルオキシ−2,3−ジヒ
ドロ−2,4,6,7−テトラメチル−1−ベ
ンゾフラン−2−イル)プロパノール[Chemical formula] (28) 3-(5-benzyloxy-2,3-dihydro-2,4,6,7-tetramethyl-1-benzofuran-2-yl)propanol
【化】
2,3−ジヒドロベンゾフラン誘導体()の
うち、一般式()においてnが1である2,3
−ジヒドロベンゾフラン誘導体は例えば次の方法
により製造することができる。[Chemical formula] Among the 2,3-dihydrobenzofuran derivatives (), 2,3 in which n is 1 in the general formula ()
-Dihydrobenzofuran derivatives can be produced, for example, by the following method.
【化】[ka]
【化】[ka]
【化】
(式中、R1及びR4は前記定義の通りであり、
R3′は水酸基の保護基を表わし、R5は低級アルキ
ル基又はアリール基を表わし、Xは水酸基、アル
コキシル基又はハロゲン原子を表わし、Yは塩素
原子、臭素原子などのハロゲン原子を表わす。
R4′は置換基を有していてもよいアルキル基又は
式[Formula, R 1 and R 4 are as defined above,
R 3 ' represents a hydroxyl protecting group, R 5 represents a lower alkyl group or aryl group, X represents a hydroxyl group, alkoxyl group or a halogen atom, and Y represents a halogen atom such as a chlorine atom or a bromine atom.
R 4 ′ is an alkyl group that may have a substituent or a formula
【化】
で表わされる基を示し、m,A及びpは前記定義
の通りである。)
すなわち、不活性ガス雰囲気下、1.0〜1.2当量
のマグネシウムと一般式()で示される臭化物
とをテトラヒドロフラン中室温〜50℃にて反応さ
せて対応するグリニヤール試薬を調製し、該反応
液に必要に応じ臭化物()に対して1.0〜1.2モ
ル当量の臭化第一銅を50℃以下で加え、次いで臭
化物()に対して1.0〜1.2モル当量の一般式
()で示されるハロゲン化アリルを反応させる
ことにより一般式()で示されるアリルベンゼ
ン誘導体を得る。得られたアリルベンゼン誘導体
()に塩化メチレン、1,2−ジクロルエタン
などの不活性溶媒中、1.0〜1.5モル当量の過安息
香酸、m−クロル過安息香酸などの過酸()を
室温にて反応させてエポキシド()とし、次い
で保護基を脱離させるとともに酸性条件下で環化
させることにより2,3−ジヒドロベンゾフラン
誘導体(−1a)を得ることができる。また、
該2,3−ジヒドロベンゾフラン誘導体(−
1a)を常法に従いエステル化することにより一
般式(−1b)で示される2,3−ジヒドロベ
ンゾフラン誘導体を得ることができる。
また一般式()においてnが1である2,3
−ジヒドロベンゾフラン誘導体は次の方法によつ
ても製造することができる。It represents a group represented by the following formula, where m, A and p are as defined above. ) That is, in an inert gas atmosphere, 1.0 to 1.2 equivalents of magnesium and a bromide represented by the general formula () are reacted in tetrahydrofuran at room temperature to 50°C to prepare the corresponding Grignard reagent, and the reaction solution contains the necessary components. Add 1.0 to 1.2 molar equivalents of cuprous bromide to the bromide () at 50°C or lower, and then add 1.0 to 1.2 molar equivalents of the allyl halide represented by the general formula () to the bromide (). By the reaction, an allylbenzene derivative represented by the general formula () is obtained. The obtained allylbenzene derivative () is treated with 1.0 to 1.5 molar equivalents of a peracid () such as perbenzoic acid or m-chloroperbenzoic acid in an inert solvent such as methylene chloride or 1,2-dichloroethane at room temperature. A 2,3-dihydrobenzofuran derivative (-1a) can be obtained by reacting to form an epoxide (), followed by removing the protecting group and cyclizing under acidic conditions. Also,
The 2,3-dihydrobenzofuran derivative (-
A 2,3-dihydrobenzofuran derivative represented by general formula (-1b) can be obtained by esterifying 1a) according to a conventional method. Also, in the general formula (), 2,3 where n is 1
-Dihydrobenzofuran derivatives can also be produced by the following method.
【化】[ka]
【化】[ka]
【化】[ka]
【化】
(式中、Y,R1,R4,R4′及びR5は前記定義の
通りであり、R3″は酸性条件下及び塩基性条件下
において脱保護反応を受けないベンジル基などの
水酸基の保護基を表わし、R3は酸性条件下又
は塩基性条件下において脱保護反応を受ける水酸
基の保護基を表わす。)
すなわち、不活性ガス雰囲気下で一般式()
で示されるフエノール誘導体に1.0〜1.2モル当量
の水酸化リチウム、水酸化ナトリウムなどの苛性
アルカリを反応させてフエノキシドとしたのち、
一般式()で示されるハロゲン化アリルをヨウ
化ナトリウム、ヨウ化テトラブチルアンモニウム
などのヨウ素イオンの存在下にトルエン、ベンゼ
ン、ヘキサン等の非極性溶媒中で反応させること
によりアリルベンゼン誘導体()を得る。次い
で常法に従いフエノール性水酸基をアセチル化、
プロピオニル化、ベンゾイル化、メトキシメチル
化、1−エトキシエチル化などの方法により保護
したのち、塩化メチレン、1,2−ジクロルエタ
ンなどの不活性溶媒中、1.0〜1.5モル当量の過安
息香酸、m−クロル過安息香酸などの過酸()
を室温にて反応させてエポキシド()′とする。
該エポキシドに、メタノール、エタノールなどの
低級アルコールと水との混合溶媒中で、1.0〜1.5
モル当量の水酸化ナトリウム、水酸化カリウムな
どの苛性アルカリ又は0.01〜10モル当量の塩化水
素、硫酸などの鉱酸を作用させて保護基を除去
し、メタノール、エタノールなどの低級アルコー
ル中で0.01〜10モル当量の塩化水素、硫酸、p−
トルエンスルホン酸などの酸を用いて閉環するこ
とにより一般式(−1c)で示される2,3−ジ
ヒドロベンゾフラン誘導体を得ることができる。
また該2,3−ジヒドロベンゾフラン誘導体(
−1c)を常法に従いエステル化することにより一
般式(−1d)で示される2,3−ジヒドロベ
ンゾフラン誘導体を得ることができる。更に該
2,3−ジヒドロベンゾフラン誘導体(−1d)
を常法に従い脱保護することにより一般式(−
1b)で示される2,3−ジヒドロベンゾフラン
誘導体を得ることができる。
一般式()において、nが2である2,3−
ジヒドロベンゾフラン誘導体は例えば次の方法に
より製造することができる。[Formula, Y, R 1 , R 4 , R 4 ′ and R 5 are as defined above, and R 3 ″ is a benzyl group that does not undergo deprotection reaction under acidic or basic conditions. (R 3 represents a hydroxyl-protecting group that undergoes a deprotection reaction under acidic or basic conditions.) In other words, under an inert gas atmosphere, the general formula ()
After reacting the phenol derivative represented by with 1.0 to 1.2 molar equivalents of a caustic alkali such as lithium hydroxide or sodium hydroxide to form a phenoxide,
An allylbenzene derivative () is obtained by reacting an allyl halide represented by the general formula () in the presence of an iodine ion such as sodium iodide or tetrabutylammonium iodide in a nonpolar solvent such as toluene, benzene, or hexane. obtain. Next, the phenolic hydroxyl group was acetylated according to a conventional method,
After protection by methods such as propionylation, benzoylation, methoxymethylation, and 1-ethoxyethylation, 1.0 to 1.5 molar equivalents of perbenzoic acid, m- Peracids such as chlorperbenzoic acid ()
is reacted at room temperature to form epoxide ()'.
1.0 to 1.5 to the epoxide in a mixed solvent of lower alcohol such as methanol or ethanol and water.
The protective group is removed by the action of a molar equivalent of a caustic alkali such as sodium hydroxide or potassium hydroxide, or a mineral acid such as hydrogen chloride or sulfuric acid of 0.01 to 10 molar equivalents, and then the protective group is removed in a lower alcohol such as methanol or ethanol. 10 molar equivalents of hydrogen chloride, sulfuric acid, p-
A 2,3-dihydrobenzofuran derivative represented by the general formula (-1c) can be obtained by ring closure using an acid such as toluenesulfonic acid.
In addition, the 2,3-dihydrobenzofuran derivative (
A 2,3-dihydrobenzofuran derivative represented by the general formula (-1d) can be obtained by esterifying -1c) according to a conventional method. Furthermore, the 2,3-dihydrobenzofuran derivative (-1d)
By deprotecting according to a conventional method, the general formula (-
A 2,3-dihydrobenzofuran derivative represented by 1b) can be obtained. In the general formula (), 2,3- where n is 2
Dihydrobenzofuran derivatives can be produced, for example, by the following method.
【化】[ka]
【化】[ka]
【化】
(式中、R1,R3′,R4,R4′及びXは前記定義
の通りである。)
すなわち、不活性ガス雰囲気下、1.0〜1.2当量
のマグネシウムと一般式()で示される臭化物
をテトラヒドロフラン中、室温〜50℃にて反応さ
せて対応するグリニヤール試薬を調製し、次いで
該反応液に臭化物()に対して1.0〜1.2モル当
量の臭化第一銅を50℃以下で加え、得られた反応
液を一般式()で示されるγ−ブロモクロトン
酸エステル誘導体のテトラヒドロフラン溶液に室
温〜50℃で滴下して反応させた後、常法により保
護基を除去して一般式()で示される置換クロ
トン酸エステル誘導体を得る。この置換クロトン
酸エステル誘導体()を約200℃に加熱して一
般式()で示される2,3−ジヒドロベンゾ
フラン−2−イル酢酸エステル誘導体とし、該エ
ステル()を常法によりテトラヒドロフラン
中0.75〜1.5モル当量の水素化リチウムアルミニ
ウムで還元することにより一般式(−2a)で
示される2,3−ジヒドロベンゾフラン誘導体を
得ることができる。また、該2,3−ジヒドロベ
ンゾフラン誘導体を常法に従いエステル化するこ
とにより一般式(−2b)で示される2,3−
ジヒドロベンゾフラン誘導体を得ることができ
る。
また、一般式()においてnが3である2,
3−ジヒドロベンゾフラン誘導体は、例えば次の
方法により製造することができる。(In the formula, R 1 , R 3 ′, R 4 , R 4 ′ and X are as defined above.) That is, in an inert gas atmosphere, 1.0 to 1.2 equivalents of magnesium and the general formula () The corresponding Grignard reagent is prepared by reacting the bromide shown in tetrahydrofuran at room temperature to 50°C, and then 1.0 to 1.2 molar equivalent of cuprous bromide to the bromide () is added to the reaction solution at 50°C. The reaction solution obtained was added dropwise to a tetrahydrofuran solution of the γ-bromocrotonic acid ester derivative represented by the general formula () at room temperature to 50°C to react, and then the protecting group was removed by a conventional method. A substituted crotonic acid ester derivative represented by the general formula () is obtained. This substituted crotonic acid ester derivative () is heated to about 200°C to obtain a 2,3-dihydrobenzofuran-2-yl acetate derivative represented by the general formula (), and the ester () is dissolved in tetrahydrofuran with a A 2,3-dihydrobenzofuran derivative represented by general formula (-2a) can be obtained by reduction with 1.5 molar equivalents of lithium aluminum hydride. In addition, by esterifying the 2,3-dihydrobenzofuran derivative according to a conventional method, 2,3-
Dihydrobenzofuran derivatives can be obtained. Also, 2, where n is 3 in the general formula (),
The 3-dihydrobenzofuran derivative can be produced, for example, by the following method.
【化】[ka]
【化】[ka]
【化】[ka]
【化】[ka]
【化】
(式中、R1,R4,R4′及びXは前記定義の通り
であり、Phはフエニル基を表わす。)
すなわち、不活性ガス雰囲気下、一般式(−
2a)で示される2,3−ジヒドロベンゾフラン
誘導体に常法により1.0〜1.2モル当量の水酸化カ
リウム及び1.0〜1.2モル当量の塩化ベンジルを作
用させてベンジルエーテルを得、次いで該ベンジ
ルエーテルに対し1.0〜1.2モル当量のp−トルエ
ンスルホニルクロライドをピリジン中で作用させ
てp−トルエンスルホナートを得る。該スルホナ
ートにN,N−ジメチルホルムアミド中1.0〜1.2
モル当量のシアン化ナトリウムを作用させてニト
リルとしたのち、該ニトリルをエチレングリコー
ル−水中で水酸化カリウムにより加水分解してカ
ルボン酸とする。その後、該カルボン酸をテトラ
ヒドロフラン中、ほぼ等モルの水素化リチウムア
ルミニウムで還元してアルコールとし、次いでパ
ラジウム−炭素触媒の存在下加水素分解すること
により目的とする2,3−ジヒドロベンゾフラン
誘導体(−3a)を得る。更に該2,3−ジヒ
ドロベンゾフラン誘導体(−3a)を常法によ
りエステル化することにより2,3−ジヒドロベ
ンゾフラン誘導体(−3b)を得ることができ
る。
次に、2,3−ジヒドロベンゾフラン誘導体
()並びに対照として用いたα−トコフエロー
ル及び3,4−ジヒドロベンゾピラン誘導体につ
いてのリノール酸エチルの過酸化に対する抑制作
用の試験及びその結果を示す。
試験例 1〜12
リノール酸エチルに第1表に示す供試化合物を
それぞれ該リノール酸エチル100gに対して0.020
gを添加混合し、試料の溶液を作成した。これら
の試料の20mlをAOM(Antioxygen Method)試
験装置を用い、AOM条件下(97.8℃、通気2.33
c.c./sec)で虐待し、3.5時間後のPOV(過酸化物
価)を測定した。(In the formula, R 1 , R 4 , R 4 ' and X are as defined above, and Ph represents a phenyl group.) That is, under an inert gas atmosphere, the general formula (-
The 2,3-dihydrobenzofuran derivative represented by 2a) is reacted with 1.0 to 1.2 molar equivalents of potassium hydroxide and 1.0 to 1.2 molar equivalents of benzyl chloride to obtain benzyl ether, and then 1.0 ~1.2 molar equivalents of p-toluenesulfonyl chloride are reacted in pyridine to give p-toluenesulfonate. 1.0 to 1.2 to the sulfonate in N,N-dimethylformamide.
After reacting with a molar equivalent of sodium cyanide to form a nitrile, the nitrile is hydrolyzed with potassium hydroxide in ethylene glycol-water to form a carboxylic acid. Thereafter, the carboxylic acid is reduced to an alcohol with approximately equimolar lithium aluminum hydride in tetrahydrofuran, and then hydrolyzed in the presence of a palladium-carbon catalyst to obtain the desired 2,3-dihydrobenzofuran derivative (- Get 3a). Furthermore, the 2,3-dihydrobenzofuran derivative (-3b) can be obtained by esterifying the 2,3-dihydrobenzofuran derivative (-3a) by a conventional method. Next, a test of the inhibitory effect on peroxidation of ethyl linoleate for 2,3-dihydrobenzofuran derivative (2) and α-tocopherol and 3,4-dihydrobenzopyran derivatives used as controls and the results thereof will be shown. Test Examples 1 to 12 Add the test compounds shown in Table 1 to ethyl linoleate at 0.020 g per 100 g of the ethyl linoleate.
g was added and mixed to create a sample solution. 20 ml of these samples were tested using AOM (Antioxygen Method) test equipment under AOM conditions (97.8°C, aeration 2.33°C).
cc/sec) and the POV (peroxide value) was measured 3.5 hours later.
【表】【table】
以下に、本発明を実施例により具体的に説明す
る。なお、本発明はこれらの実施例により限定さ
れるものではない。
実施例 1
The present invention will be specifically explained below using examples. Note that the present invention is not limited to these Examples. Example 1
【化】
1 窒素雰囲気下マグネシウム4.9gにテトラヒ
ドロフラン20ml及び臭化エチル0.5mlを加え、
マグネシウムを活性化した。次いで該反応液に
2−プロモ−1,4−ビス〔1−(エトキシ)
エトキシ〕−3,5,6−トリメチルベンゼン
75gとテトラヒドロフラン200mlから成る溶液
を、反応温度を30〜40℃に保ちながら滴下し、
滴下後、同温度で1時間攪拌を続けることによ
りグリニヤール試薬のテトラヒドロフラン溶液
を調製した。
2 上記の方法により得られたグリニヤール試薬
のテトラヒドロフラン溶液に、反応温度を50℃
以下に保ちながら臭化アリル24.2gを滴下し、
滴下後、同温度にて2時間攪拌した。得られた
反応液を冷1N水酸化ナトリウム水溶液にあけ、
エチルエーテルで抽出した。エーテル抽出液を
飽和食塩水で洗滌後、無水硫酸ナトリウムで乾
燥し、次いで低沸点物を減圧下に留去して2−
アリル−1,4−ビス〔1−(エトキシ)エト
キシ〕−3,5,6−トリメチルベンゼンを得
た。
3 上記の方法により得られた2−アリル−1,
4−ビス〔1−(エトキシ)エトキシ〕−3,
5,6−トリメチルベンゼンを塩化メチレン
300mlに溶解し、30℃以下にてm−クロル過安
息香酸(純度80%)43.1gを徐々に加えた。得
られた反応液を室温で3時間攪拌した後、過
し、過にエチルエーテルを加えて重曹水、チ
オ硫酸ナトリウム水溶液、重曹水及び食塩水で
順次洗滌した。有機層を減圧下に濃縮し、得ら
れた残渣にエタノール200ml及び2N塩酸50mlを
加え、60℃に加温した。反応液を水にあけてエ
チルエーテルで抽出し、抽出液を食塩水で洗滌
後、無水硫酸ナトリウムで乾燥した。これによ
り低沸点物を減圧下に留去し、得られた残渣を
シリカゲルカラムクロマトグラフイーで精製
し、次いでエチルエーテル/ヘキサンで再結晶
することにより、下記の物性を有する(2,3
−ジヒドロ−5−ヒドロキシ−4,6,7−ト
リメチル−1−ベンゾフラン−2−イル)メタ
ノール〔化合物(1)〕を6.6g得た。
NMRスペクトル(90MHz)δHMS DMSO-d6:
1.93(s,3H);1.98(s,6H);2.56〜3.36(m,
2H);
3.46(t,J=5Hz,2H);4.4〜4.7(m,
1H);
4.79(t,J=5Hz,1H);7.33(s,1H)
FD−質量スペクトル
〔M〕+208
実施例 2[Chemical formula] 1 Add 20 ml of tetrahydrofuran and 0.5 ml of ethyl bromide to 4.9 g of magnesium under a nitrogen atmosphere,
Activated magnesium. Next, 2-promo-1,4-bis[1-(ethoxy)
ethoxy]-3,5,6-trimethylbenzene
A solution consisting of 75 g and 200 ml of tetrahydrofuran was added dropwise while maintaining the reaction temperature at 30 to 40°C.
After the dropwise addition, stirring was continued for 1 hour at the same temperature to prepare a solution of Grignard reagent in tetrahydrofuran. 2 Add the Grignard reagent obtained by the above method to the tetrahydrofuran solution at a reaction temperature of 50°C.
24.2g of allyl bromide was added dropwise while keeping the temperature below.
After the dropwise addition, the mixture was stirred at the same temperature for 2 hours. Pour the obtained reaction solution into a cold 1N aqueous sodium hydroxide solution,
Extracted with ethyl ether. The ether extract was washed with saturated brine, dried over anhydrous sodium sulfate, and then low-boiling substances were distilled off under reduced pressure to obtain 2-
Allyl-1,4-bis[1-(ethoxy)ethoxy]-3,5,6-trimethylbenzene was obtained. 3 2-allyl-1 obtained by the above method,
4-bis[1-(ethoxy)ethoxy]-3,
5,6-trimethylbenzene to methylene chloride
43.1 g of m-chloroperbenzoic acid (purity 80%) was gradually added to the solution at 30° C. or lower. The resulting reaction solution was stirred at room temperature for 3 hours, filtered, added with excess ethyl ether, and washed successively with aqueous sodium bicarbonate, aqueous sodium thiosulfate, aqueous sodium bicarbonate, and brine. The organic layer was concentrated under reduced pressure, and 200 ml of ethanol and 50 ml of 2N hydrochloric acid were added to the resulting residue, and the mixture was heated to 60°C. The reaction solution was poured into water and extracted with ethyl ether. The extract was washed with brine and dried over anhydrous sodium sulfate. As a result, low-boiling substances were distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography, and then recrystallized from ethyl ether/hexane, which had the following physical properties (2,3
6.6 g of -dihydro-5-hydroxy-4,6,7-trimethyl-1-benzofuran-2-yl)methanol [compound (1)] was obtained. NMR spectrum (90MHz) δ HMS DMSO-d6 : 1.93 (s, 3H); 1.98 (s, 6H); 2.56-3.36 (m,
2H); 3.46 (t, J=5Hz, 2H); 4.4-4.7 (m,
1H); 4.79 (t, J=5Hz, 1H); 7.33 (s, 1H) FD-Mass spectrum [M] + 208 Example 2
【化】[ka]
【化】
1 実施例1−1と同様に反応させることにより
グリニヤール試薬のテトラヒドロフラン溶液を
得た。
2 該グリニヤール試薬のテトラヒドロフラン溶
液に臭化第一銅28.7gを反応液が40℃を越えな
いように加え、添加後同温度で1時間攪拌し、
有機銅試薬のテトラヒドロフラン懸濁液を調製
した。
3 上記により得られた有機銅試薬のテトラヒド
ロフラン懸濁液に塩化メタリル18.1gを50℃を
越えないように滴下し、滴下後同温度で2時間
攪拌した。得られた反応液を1N水酸化ナトリ
ウム水溶液にあけ、エチルエーテルを加えてセ
ライトを通して過した。液を分液し、有機
層を食塩水で洗滌後、無水硫酸ナトリウムで乾
燥した。これにより低沸点物を減圧下に留去す
ることにより1,4−ビス〔1−(エトキシ)
エトキシ〕−3,5,6−トリメチル−2−(2
−メチル−2−プロペニル)ベンゼンを得た。
4 実施例1−3において2−アリル−1,4−
ビス〔1−(エトキシ)エトキシ〕−3,5,6
−トリメチルベンゼンの代りに上記の方法によ
り得られた1,4−ビス〔1−(エトキシ)エ
トキシ〕−3,5,6−トリメチル−2−(2−
メチル−2−プロペニル)ベンゼンを用いた以
外は実施例1−3と同様に反応及び精製を行な
うことにより、下記の物性を有する(2,3−
ジヒドロ−5−ヒドロキシ−2,4,6,7−
テトラメチル−1−ベンゾフラン−2−イル)
メタノール〔化合物(2)〕を25.5g得た。
NMRスペクトル(90MHz)δHMS CDCl3:
1.33(s,3H);2.03(s,10H);
2.72(d,J=16Hz,1H);3.08(d,J=16Hz,
1H);
3.3(br.s,1H);3.53(s,2H)
FD質量スペクトル
〔M〕+222
実施例 3embedded image 1 A solution of a Grignard reagent in tetrahydrofuran was obtained by reacting in the same manner as in Example 1-1. 2 Add 28.7 g of cuprous bromide to the tetrahydrofuran solution of the Grignard reagent so that the temperature of the reaction solution does not exceed 40°C, and stir at the same temperature for 1 hour after addition.
A suspension of organocopper reagent in tetrahydrofuran was prepared. 3. To the tetrahydrofuran suspension of the organocopper reagent obtained above, 18.1 g of methallyl chloride was added dropwise so as not to exceed 50°C, and after the dropwise addition, the suspension was stirred at the same temperature for 2 hours. The resulting reaction solution was poured into a 1N aqueous sodium hydroxide solution, ethyl ether was added, and the mixture was filtered through Celite. The liquid was separated, and the organic layer was washed with brine and dried over anhydrous sodium sulfate. By distilling off the low boiling point substances under reduced pressure, 1,4-bis[1-(ethoxy)]
ethoxy]-3,5,6-trimethyl-2-(2
-methyl-2-propenyl)benzene was obtained. 4 In Example 1-3, 2-allyl-1,4-
Bis[1-(ethoxy)ethoxy]-3,5,6
-1,4-bis[1-(ethoxy)ethoxy]-3,5,6-trimethyl-2-(2-
By performing the reaction and purification in the same manner as in Example 1-3 except for using methyl-2-propenyl)benzene, (2,3-propenyl) having the following physical properties was obtained.
dihydro-5-hydroxy-2,4,6,7-
tetramethyl-1-benzofuran-2-yl)
25.5 g of methanol [compound (2)] was obtained. NMR spectrum (90MHz) δ HMS CDCl3 : 1.33 (s, 3H); 2.03 (s, 10H); 2.72 (d, J = 16Hz, 1H); 3.08 (d, J = 16Hz,
1H); 3.3 (br.s, 1H); 3.53 (s, 2H) FD mass spectrum [M] + 222 Example 3
【化】[ka]
【化】
1 実施例1−1と同様に反応させることにより
グリニヤール試薬のテトラヒドロフラン溶液を
調製した。
2 実施例2−2と同様に反応させることにより
有機銅試薬のテトラヒドロフラン懸濁液を得
た。
3 4−ブロモ−3−メチル−2−ブテン酸メチ
ル38.6gとテトラヒドロフラン200mlから成る
溶液に40℃以下にて上記により得られた有機銅
試薬のテトラヒドロフラン懸濁液を滴下し、同
温度で3時間攪拌した。得られた反応液を2N
塩酸にあけ、約50℃に加温したのち冷却しエチ
ルエーテルで抽出した。抽出液を無水硫酸ナト
リウムで乾燥し、これより低沸点物を留去して
得られる残渣を減圧下約200℃に加熱して蒸留
した。留出物をシリカゲルカラムクロマトグラ
フイーで精製して(2,3−ジヒドロ−5−ヒ
ドロキシ−2,4,6,7−テトラメチル−1
−ベンゾフラン−2−イル)酢酸メチル17.2g
を得た。
4 上記の方法により得られた(2,3−ジヒド
ロ−5−ヒドロキシ−2,4,6,7−テトラ
メチル−1−ベンゾフラン−2−イル)酢酸メ
チル9.5gとテトラヒドロフラン50mlから成る
溶液を、水素化リチウムアルミニウム1.4gと
テトラヒドロフラン200mlから成る懸濁液に加
熱還流下で滴下した。滴下後、約30分間加熱還
流を続けたのち冷却し、氷水に徐々に加えた。
希塩酸を加えて酸性としたのち塩化メチレンで
抽出し、抽出液を無水硫酸ナトリウムで乾燥し
た。これにより低沸点物を減圧下に留去したの
ち、シリカゲルカラムクロマトグラフイーで精
製することにより下記の物性を有する2−(2,
3−ジヒドロ−5−ヒドロキシ−2,4,6,
7−テトラメチル−1−ベンゾフラン−2−イ
ル)エタノール〔化合物(4)〕を3.5g得た。
NMRスペクトル(90MHz)δHMS CDCl3:
1.4(s,3H);1.65〜2.2(m,12H);2.78(d,
J=15Hz,1H);3.0(d,J=15Hz、1H);3.55
〜4.0(m,2H);4.2(br.s,1H)
FD質量スペクトル
〔M〕+236
実施例 4embedded image 1 A tetrahydrofuran solution of a Grignard reagent was prepared by reacting in the same manner as in Example 1-1. 2 A suspension of an organocopper reagent in tetrahydrofuran was obtained by reacting in the same manner as in Example 2-2. 3. To a solution consisting of 38.6 g of methyl 4-bromo-3-methyl-2-butenoate and 200 ml of tetrahydrofuran, the suspension of the organocopper reagent obtained above in tetrahydrofuran was added dropwise at 40°C or below, and the suspension was heated at the same temperature for 3 hours. Stirred. The obtained reaction solution was diluted with 2N
The mixture was poured into hydrochloric acid, heated to about 50°C, cooled, and extracted with ethyl ether. The extract was dried over anhydrous sodium sulfate, and the residue obtained by distilling off low-boiling substances was distilled under reduced pressure by heating to about 200°C. The distillate was purified by silica gel column chromatography (2,3-dihydro-5-hydroxy-2,4,6,7-tetramethyl-1
-Benzofuran-2-yl)methyl acetate 17.2g
I got it. 4 A solution consisting of 9.5 g of methyl (2,3-dihydro-5-hydroxy-2,4,6,7-tetramethyl-1-benzofuran-2-yl)acetate obtained by the above method and 50 ml of tetrahydrofuran, The mixture was added dropwise to a suspension consisting of 1.4 g of lithium aluminum hydride and 200 ml of tetrahydrofuran under heating under reflux. After the dropwise addition, the mixture was heated under reflux for about 30 minutes, cooled, and gradually added to ice water.
The mixture was made acidic by adding dilute hydrochloric acid, extracted with methylene chloride, and the extract was dried over anhydrous sodium sulfate. After distilling off the low boiling point substances under reduced pressure, the 2-(2,
3-dihydro-5-hydroxy-2,4,6,
3.5 g of 7-tetramethyl-1-benzofuran-2-yl)ethanol [compound (4)] was obtained. NMR spectrum (90MHz) δ HMS CDCl3 : 1.4 (s, 3H); 1.65-2.2 (m, 12H); 2.78 (d,
J=15Hz, 1H); 3.0 (d, J=15Hz, 1H); 3.55
~4.0 (m, 2H); 4.2 (br.s, 1H) FD mass spectrum [M] + 236 Example 4
【化】[ka]
【化】
1 実施例1−1と同様に反応させることにより
グリニヤール試薬のテトラヒドロフラン溶液を
調製した。
2 実施例2−2と同様に反応させることにより
有機銅試薬のテトラヒドロフラン懸濁液を得
た。
3 4−ブロモ−2−ブテン酸メチル35.8gとテ
トラヒドロフラン200mlから成る溶液に40℃以
下にて上記により得られた有機銅試薬のテトラ
ヒドロフラン懸濁液を滴下し、同温度で3時間
攪拌した。得られた反応液を2N塩酸にあけ、
約50℃に加温したのち冷却し、エチルエーテル
で抽出した。抽出液を無水硫酸ナトリウムで乾
燥し、これより低沸点物を留去して得られる残
渣を減圧下約200℃に加熱して蒸留した。留出
物をシリカゲルカラムクロマトグラフイーで精
製して(2,3−ジヒドロ−5−ヒドロキシ−
4,6,7−トリメチル−1−ベンゾフラン−
2−イル)酢酸メチルを14.3g得た。
4 実施例3−4において(2,3−ジヒドロ−
5−ヒドロキシ−2,4,6,7−テトラメチ
ル−1−ベンゾフラン−2−イル)酢酸メチル
9.5gの代りに(2,3−ジヒドロ−5−ヒド
ロキシ−4,6,7−トリメチル−1−ベンゾ
フラン−2−イル)酢酸メチル9.0gを用いた
以外は実施例3−4と同様に反応及び分離精製
を行なうことにより、下記の物性を有する2−
(2,3−ジヒドロ−5−ヒドロキシ−4,6,
7−トリメチル−1−ベンゾフラン−2−イ
ル)エタノール〔化合物(3)〕を2.0g得た。
NMRスペクトル(90MHz)δHMS CDCl3:
1.65〜2.2(m,12H);2.55〜3.2(m,2H);
3.55〜4.0(m,2H);4.1(br.s,1H);
4.35〜4.7(m,1H)
FD質量スペクトル
〔M〕+222
実施例 5embedded image 1 A tetrahydrofuran solution of a Grignard reagent was prepared by reacting in the same manner as in Example 1-1. 2 A suspension of an organocopper reagent in tetrahydrofuran was obtained by reacting in the same manner as in Example 2-2. 3. To a solution consisting of 35.8 g of methyl 4-bromo-2-butenoate and 200 ml of tetrahydrofuran, the suspension of the organocopper reagent obtained above in tetrahydrofuran was added dropwise at 40° C. or lower, and the mixture was stirred at the same temperature for 3 hours. Pour the obtained reaction solution into 2N hydrochloric acid,
After heating to about 50°C, the mixture was cooled and extracted with ethyl ether. The extract was dried over anhydrous sodium sulfate, and the residue obtained by distilling off low-boiling substances was distilled under reduced pressure by heating to about 200°C. The distillate was purified by silica gel column chromatography (2,3-dihydro-5-hydroxy-
4,6,7-trimethyl-1-benzofuran-
14.3 g of methyl 2-yl) acetate was obtained. 4 In Example 3-4, (2,3-dihydro-
Methyl 5-hydroxy-2,4,6,7-tetramethyl-1-benzofuran-2-yl)acetate
The reaction was carried out in the same manner as in Example 3-4, except that 9.0 g of methyl (2,3-dihydro-5-hydroxy-4,6,7-trimethyl-1-benzofuran-2-yl)acetate was used instead of 9.5 g. By performing separation and purification, 2-
(2,3-dihydro-5-hydroxy-4,6,
2.0 g of 7-trimethyl-1-benzofuran-2-yl)ethanol [compound (3)] was obtained. NMR spectrum (90MHz) δ HMS CDCl3 : 1.65-2.2 (m, 12H); 2.55-3.2 (m, 2H); 3.55-4.0 (m, 2H); 4.1 (br.s, 1H); 4.35-4.7 (m , 1H) FD mass spectrum [M] + 222 Example 5
【化】[ka]
【化】[ka]
【化】[ka]
【化】[ka]
【式】
1 窒素雰囲気下2−(2,3−ジヒドロ−5−
ヒドロキシ−2,4,6,7−テトラメチル−
1−ベンゾフラン−2−イル)エタノール4.72
g(20mmol)とエタノール50mlから成る溶液
に水酸化カリウム1.34g(24mmol)と水3ml
から成る溶液を加え、室温で1時間攪拌したの
ち減圧下に低沸点物を留去した。得られた残渣
をN,N−ジメチルホルムアミド50mlに溶解
し、塩化ベンジル2.8g(22mmol)を加えて、
約60℃で1時間加熱した。反応液を希塩酸にあ
けてエチルエーテルで抽出し、抽出液を食塩水
で洗滌後、無水硫酸ナトリウムで乾燥した。こ
れより減圧下に低沸点物を留去し、得られた残
渣をシリカゲルカラムクロマトグラフイーで精
製することにより2−(5−ベンジルオキシ−
2,3−ジヒドロ−2,4,6,7−テトラメ
チル−1−ベンゾフラン−2−イル)エタノー
ル〔化合物(27)〕4.56gを得た。
2 上記の方法により得た2−(5−ベンジルオ
キシ−2,3−ジヒドロ−2,4,6,7−テ
トラメチル−1−ベンゾフラン−2−イル)エ
タノール4.56g(14mmol)をピリジン50mlに
溶解し、氷冷下p−トリエンスルホニルクロラ
イド2.9gを加え、更に室温で3時間攪拌を続
けた。得られた反応液を水にあけてエチルエー
テルで抽出し、抽出液を希塩酸及び食塩水で順
次洗滌した後、無水硫酸ナトリウムで乾燥し
た。これより低沸点物を減圧下に留去し、得ら
れた残渣をシリカゲルカラムクロマトグラフイ
ーで精製することにより2−(5−ベンジルオ
キシ−2,3−ジヒドロ−2,4,6,7−テ
トラメチル−1−ベンゾフラン−2−イル)エ
チル p−トルエンスルホナートを4.80g得
た。
3 上記の方法により得られた2−(5−ベンジ
ルオキシ−2,3−ジヒドロ−2,4,6,7
−テトラメチル−1−ベンゾフラン−2−イ
ル)エチル p−トルエンスルホナートを4.80
gをN,N−ジメチルホルムアミド50mlに溶解
し、シアン化ナトリウム0.60gを加えて約60℃
で3時間攪拌した。得られた反応液を水にあけ
てエチルエーテルで抽出し、抽出液を食塩水で
洗滌後、無水硫酸ナトリウムで乾燥した。これ
より減圧下に低沸点物を留去し、得られた残渣
をシリカゲルカラムクロマトグラフイーで精製
することにより3−(5−ベンジルオキシ−2,
3−ジヒドロ−2,4,6,7−テトラメチル
−1−ベンゾフラン−2−イル)プロピオニト
リルを2.97g得た。
4 上記により得られた3−(5−ベンジルオキ
シ−2,3−ジヒドロ−2,4,6,7−テト
ラメチル−1−ベンゾフラン−2−イル)プロ
ピオニトリルを2.97g、エチレングリコール
100ml及び20%水酸化カリウム水溶液20mlから
成る溶液を窒素雰囲気下で一夜加熱還流した。
得られた反応液を冷却後、希塩酸にあけてエチ
ルエーテルで抽出した。抽出液を水及び飽和食
塩水で順次洗滌し、無水硫酸ナトリウムで乾燥
した。これより減圧下に低沸点物を留去し、得
られた残渣をシリカゲルカラムクロマトグラフ
イーで精製することにより3−(5−ベンジル
オキシ−2,3−ジヒドロ−2,4,6,7−
テトラメチル−1−ベンゾフラン−2−イル)
プロピオン酸を1.90g得た。
5 上記により得られた3−(5−ベンジルオキ
シ−2,3−ジヒドロ−2,4,6,7−テト
ラメチル−1−ベンゾフラン−2−イル)プロ
ピオン酸1.84gをテトラヒドロフラン50mlに溶
解し、水素化リチウムアルミニウム0.38gとテ
トラヒドロフラン100mlから成る溶液に加熱還
流下で滴下した。滴下後1時間加熱還流したの
ち冷却し、得られた反応液を氷水にあけ、希塩
酸を加えてエチルエーテルで抽出した。抽出液
を食塩水で洗滌し、無水硫酸ナトリウムで乾燥
したのち低沸点物を減圧下に留去した。得られ
た残渣をシリカゲルカラムクロマトグラフイー
で精製することにより3−(5−ベンジルオキ
シ−2,3−ジヒドロ−2,4,6,7−テト
ラメチル−1−ベンゾフラン−2−イル)プロ
パノール〔化合物(28)〕を1.39g得た。
6 上記の方法により得られた3−(5−ベンジ
ルオキシ−2,3−ジヒドロ−2,4,6,7
−テトラメチル−1−ベンゾフラン−2−イ
ル)プロパノール1.36gをエタノール50mlに溶
解し、濃塩酸2滴及び3%パラジウム−炭素
0.5gを加えて水素雰囲気下、室温で2日間攪
拌した。得られた反応液を過したのち低沸点
物を減圧下に留去し、得られた残渣をシリカゲ
ルカラムクロマトグラフイーで精製することに
より下記の物性を有する3−(2,3−ジヒド
ロ−5−ヒドロキシ−2,4,6,7−テトラ
メチル−1−ベンゾフラン−2−イル)プロパ
ノール〔化合物(6)〕を0.9g得た。
NMRスペクトル(90MHz)δHMS CDCl3:
1.4(s,3H);1.5〜2.2(m,13H);2.72(d,
J=15Hz、1H);3.0(d,J=15Hz,1H);3.3
(br.s,2H);3.4〜3.8(m,2H)
FD質量スペクトル
〔M〕+250
実施例 6[Formula] 1 2-(2,3-dihydro-5-
Hydroxy-2,4,6,7-tetramethyl-
1-Benzofuran-2-yl) ethanol 4.72
Potassium hydroxide 1.34 g (24 mmol) and water 3 ml in a solution consisting of g (20 mmol) and 50 ml of ethanol.
After stirring at room temperature for 1 hour, low-boiling substances were distilled off under reduced pressure. The obtained residue was dissolved in 50 ml of N,N-dimethylformamide, and 2.8 g (22 mmol) of benzyl chloride was added.
It was heated at about 60°C for 1 hour. The reaction solution was poured into dilute hydrochloric acid and extracted with ethyl ether. The extract was washed with brine and dried over anhydrous sodium sulfate. From this, low-boiling substances were distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography to obtain 2-(5-benzyloxy-
4.56 g of 2,3-dihydro-2,4,6,7-tetramethyl-1-benzofuran-2-yl)ethanol [compound (27)] was obtained. 2 Add 4.56 g (14 mmol) of 2-(5-benzyloxy-2,3-dihydro-2,4,6,7-tetramethyl-1-benzofuran-2-yl)ethanol obtained by the above method to 50 ml of pyridine. After dissolving, 2.9 g of p-trienesulfonyl chloride was added under ice-cooling, and stirring was continued for 3 hours at room temperature. The resulting reaction solution was poured into water and extracted with ethyl ether. The extract was washed successively with dilute hydrochloric acid and brine, and then dried over anhydrous sodium sulfate. From this, low-boiling substances were distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography to obtain 2-(5-benzyloxy-2,3-dihydro-2,4,6,7- 4.80 g of tetramethyl-1-benzofuran-2-yl)ethyl p-toluenesulfonate was obtained. 3 2-(5-benzyloxy-2,3-dihydro-2,4,6,7 obtained by the above method)
-tetramethyl-1-benzofuran-2-yl)ethyl p-toluenesulfonate 4.80
Dissolve g in 50 ml of N,N-dimethylformamide, add 0.60 g of sodium cyanide, and heat at about 60°C.
The mixture was stirred for 3 hours. The resulting reaction solution was poured into water and extracted with ethyl ether. The extract was washed with brine and dried over anhydrous sodium sulfate. From this, low-boiling substances were distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography to obtain 3-(5-benzyloxy-2,
2.97 g of 3-dihydro-2,4,6,7-tetramethyl-1-benzofuran-2-yl)propionitrile was obtained. 4 2.97 g of 3-(5-benzyloxy-2,3-dihydro-2,4,6,7-tetramethyl-1-benzofuran-2-yl)propionitrile obtained above, ethylene glycol
A solution consisting of 100 ml and 20 ml of 20% aqueous potassium hydroxide solution was heated to reflux under nitrogen atmosphere overnight.
After cooling the resulting reaction solution, it was poured into dilute hydrochloric acid and extracted with ethyl ether. The extract was washed successively with water and saturated brine, and dried over anhydrous sodium sulfate. From this, low-boiling substances were distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography to obtain 3-(5-benzyloxy-2,3-dihydro-2,4,6,7-
tetramethyl-1-benzofuran-2-yl)
1.90g of propionic acid was obtained. 5 Dissolve 1.84 g of 3-(5-benzyloxy-2,3-dihydro-2,4,6,7-tetramethyl-1-benzofuran-2-yl)propionic acid obtained above in 50 ml of tetrahydrofuran, The mixture was added dropwise to a solution consisting of 0.38 g of lithium aluminum hydride and 100 ml of tetrahydrofuran under heating under reflux. After the dropwise addition, the mixture was heated under reflux for 1 hour and then cooled. The resulting reaction solution was poured into ice water, diluted hydrochloric acid was added, and the mixture was extracted with ethyl ether. The extract was washed with brine, dried over anhydrous sodium sulfate, and then low-boiling substances were distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 3-(5-benzyloxy-2,3-dihydro-2,4,6,7-tetramethyl-1-benzofuran-2-yl)propanol [ 1.39 g of Compound (28)] was obtained. 6 3-(5-benzyloxy-2,3-dihydro-2,4,6,7 obtained by the above method)
Dissolve 1.36 g of -tetramethyl-1-benzofuran-2-yl)propanol in 50 ml of ethanol, add 2 drops of concentrated hydrochloric acid and 3% palladium-carbon.
0.5 g was added thereto, and the mixture was stirred at room temperature for 2 days under a hydrogen atmosphere. After filtering the obtained reaction solution, low-boiling substances were distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography to obtain 3-(2,3-dihydro-5) having the following physical properties. 0.9 g of -hydroxy-2,4,6,7-tetramethyl-1-benzofuran-2-yl)propanol [compound (6)] was obtained. NMR spectrum (90MHz) δ HMS CDCl3 : 1.4 (s, 3H); 1.5-2.2 (m, 13H); 2.72 (d,
J=15Hz, 1H); 3.0 (d, J=15Hz, 1H); 3.3
(br.s, 2H); 3.4-3.8 (m, 2H) FD mass spectrum [M] + 250 Example 6
【化】[ka]
【化】[ka]
【化】[ka]
【化】
1 実施例5−1において2−(2,3−ジヒド
ロ−5−ヒドロキシ−2,4,6,7−テトラ
メチル−1−ベンゾフラン−2−イル)エタノ
ール4.72gの代りに2−(2,3−ジヒドロ−
5−ヒドロキシ−4,6,7−トリメチル−1
−ベンゾフラン−2−イル)エタノール4.44g
を用いた以外は実施例5−1と同様に反応及び
分離精製を行なうことにより2−(5−ベンジ
ルオキシ−2,3−ジヒドロ−4,6,7−ト
リメチル−1−ベンゾフラン−2−イル)エタ
ノール4.4gを得た。
2 実施例5−2において2−(5−ベンジルオ
キシ−2,3−ジヒドロ−2,4,6,7−テ
トラメチル−1−ベンゾフラン−2−イル)エ
タノール4.56gの代りに2−(5−ベンジルオ
キシ−2,3−ジヒドロ−4,6,7−トリメ
チル−1−ベンゾフラン−2−イル)エタノー
ル4.37g用いた以外は実施例5−2と同様に反
応及び分離精製を行なうことにより2−(5−
ベンジルオキシ−2,3−ジヒドロ−4,6,
7−トリメチル−1−ベンゾフラン−2−イ
ル)エチル p−トルエンスルホナートを4.70
g得た。
3 実施例5−3において2−(5−ベンジルオ
キシ−2,3−ジヒドロ−2,4,6,7−テ
トラメチル−1−ベンゾフラン−2−イル)エ
チル p−トルエンスルホナート4.80gの代り
に2−(5−ベンジルオキシ−2,3−ジヒド
ロ−4,6,7−トリメチル−1−ベンゾフラ
ン−2−イル)エチル p−トルエンスルホナ
ート4.66gを用いた以外は実施例5−3と同様
に反応及び分離精製を行なうことにより3−
(5−ベンジルオキシ−2,3−ジヒドロ−4,
6,7−トリメチル−1−ベンゾフラン−2−
イル)プロピオニトリルを2.8g得た。
4 実施例5−4において3−(5−ベンジルオ
キシ−2,3−ジヒドロ−2,4,6,7−テ
トラメチル−1−ベンゾフラン−2−イル)プ
ロピオニトリル2.97gの代りに3−(5−ベン
ジルオキシ−2,3−ジヒドロ−4,6,7−
トリメチル−1−ベンゾフラン−2−イル)プ
ロピオニトリル2.85gを用いた以外は実施例5
−4と同様に反応及び分離精製を行なうことに
より3−(5−ベンジルオキシ−2,3−ジヒ
ドロ−4,6,7−トリメチル−1−ベンゾフ
ラン−2−イル)プロピオン酸を1.92g得た。
5 実施例5−5において3−(5−ベンジルオ
キシ−2,3−ジヒドロ−2,4,6,7−テ
トラメチル−1−ベンゾフラン−2−イル)プ
ロピオン酸1.84gの代りに3−(5−ベンジル
オキシ−2,3−ジヒドロ−4,6,7−トリ
メチル−1−ベンゾフラン−2−イル)プロピ
オン酸1.77gを用いた以外は実施例5−5と同
様に反応及び分離精製を行なうことにより3−
(5−ベンジルオキシ−2,3−ジヒドロ−4,
6,7−トリメチル−1−ベンゾフラン−2−
イル)プロパノールを1.38g得た。
6 実施例5−6において3−(5−ベンジルオ
キシ−2,3−ジヒドロ−2,4,6,7−テ
トラメチル−1−ベンゾフラン−2−イル)プ
ロパノール1.36gの代りに3−(5−ベンジル
オキシ−2,3−ジヒドロ−4,6,7−トリ
メチル−1−ベンゾフラン−2−イル)プロパ
ノール1.30gを用いた以外は実施例5−6と同
様に反応及び分離精製を行なうことにより、下
記のFD質量スペクトルを有する3−(2,3−
ジヒドロ−5−ヒドロキシ−4,6,7−トリ
メチル−1−ベンゾフラン−2−イル)プロパ
ノール〔化合物(5)〕を0.86g得た。
FD質量スペクトル
〔M〕+236
実施例 7[Chemical formula] 1 In Example 5-1, 2-(2,3-dihydro-5-hydroxy-2,4,6,7-tetramethyl-1-benzofuran-2-yl)ethanol was replaced with 4.72 g. (2,3-dihydro-
5-hydroxy-4,6,7-trimethyl-1
-Benzofuran-2-yl)ethanol 4.44g
2-(5-benzyloxy-2,3-dihydro-4,6,7-trimethyl-1-benzofuran-2-yl ) 4.4 g of ethanol was obtained. 2 In Example 5-2, 2-(5-benzyloxy-2,3-dihydro-2,4,6,7-tetramethyl-1-benzofuran-2-yl)ethanol was replaced with 4.56 g. -Benzyloxy-2,3-dihydro-4,6,7-trimethyl-1-benzofuran-2-yl) ethanol was used in the same manner as in Example 5-2, except that 4.37 g of ethanol was used. -(5-
benzyloxy-2,3-dihydro-4,6,
7-trimethyl-1-benzofuran-2-yl)ethyl p-toluenesulfonate 4.70
I got g. 3 In Example 5-3, instead of 4.80 g of 2-(5-benzyloxy-2,3-dihydro-2,4,6,7-tetramethyl-1-benzofuran-2-yl)ethyl p-toluenesulfonate Example 5-3 except that 4.66 g of 2-(5-benzyloxy-2,3-dihydro-4,6,7-trimethyl-1-benzofuran-2-yl)ethyl p-toluenesulfonate was used. By performing the same reaction and separation and purification, 3-
(5-benzyloxy-2,3-dihydro-4,
6,7-trimethyl-1-benzofuran-2-
2.8 g of propionitrile was obtained. 4 In Example 5-4, 2.97 g of 3-(5-benzyloxy-2,3-dihydro-2,4,6,7-tetramethyl-1-benzofuran-2-yl)propionitrile was replaced with 3- (5-benzyloxy-2,3-dihydro-4,6,7-
Example 5 except that 2.85 g of trimethyl-1-benzofuran-2-yl)propionitrile was used.
1.92g of 3-(5-benzyloxy-2,3-dihydro-4,6,7-trimethyl-1-benzofuran-2-yl)propionic acid was obtained by performing the reaction and separation and purification in the same manner as in -4. . 5 In Example 5-5, 3-( The reaction and separation and purification were carried out in the same manner as in Example 5-5, except that 1.77 g of 5-benzyloxy-2,3-dihydro-4,6,7-trimethyl-1-benzofuran-2-yl)propionic acid was used. Possibly 3-
(5-benzyloxy-2,3-dihydro-4,
6,7-trimethyl-1-benzofuran-2-
1.38g of il)propanol was obtained. 6 In Example 5-6, 3-(5-benzyloxy-2,3-dihydro-2,4,6,7-tetramethyl-1-benzofuran-2-yl)propanol was replaced with 1.36 g. By carrying out the reaction and separation and purification in the same manner as in Example 5-6, except that 1.30 g of -benzyloxy-2,3-dihydro-4,6,7-trimethyl-1-benzofuran-2-yl)propanol was used. , 3-(2,3-
0.86 g of dihydro-5-hydroxy-4,6,7-trimethyl-1-benzofuran-2-yl)propanol [compound (5)] was obtained. FD mass spectrum [M] + 236 Example 7
【化】
窒素雰囲気下で(2,3−ジヒドロ−5−ヒド
ロキシ−2,4,6,7−テトラメチル−1−ベ
ンゾフラン−2−イル)メタノール0.222g
(1mmol),3,3′−チオジプロピオン酸0.89g
(0.5mmol)、トルエン15ml及びp−トルエンスル
ホン酸0.01gから成る混合液を加熱し、生成する
水を共沸混合物として系外へ除去した。得られた
反応液を減圧下に濃縮し、シリカゲルカラムクロ
マトグラフイーで精製することにより、下記の物
性を有するジ〔(2,3−ジヒドロ−5−ヒドロ
キシ−2,4,6,7−テトラメチル−1−ベン
ゾフラン−2−イル)メチル〕3,3′−チオジプ
ロピオネート〔化合物(8)〕を0.24g得た。
NMRスペクトル(90MHz)δHMS CDCl3:
1.4(s,6H);2.03(s,18H);2.35〜3.1(m,
12H);
4.07(s,4H);4.2(br.s,2H)
FD質量スペクトル
〔M〕+586
実施例 8[Chemical formula] 0.222 g of (2,3-dihydro-5-hydroxy-2,4,6,7-tetramethyl-1-benzofuran-2-yl)methanol under nitrogen atmosphere
(1mmol), 3,3'-thiodipropionic acid 0.89g
(0.5 mmol), 15 ml of toluene, and 0.01 g of p-toluenesulfonic acid was heated, and the produced water was removed from the system as an azeotrope. The resulting reaction solution was concentrated under reduced pressure and purified by silica gel column chromatography to obtain di[(2,3-dihydro-5-hydroxy-2,4,6,7-tetra) having the following physical properties. 0.24 g of methyl-1-benzofuran-2-yl)methyl]3,3'-thiodipropionate [compound (8)] was obtained. NMR spectrum (90MHz) δ HMS CDCl3 : 1.4 (s, 6H); 2.03 (s, 18H); 2.35-3.1 (m,
12H); 4.07 (s, 4H); 4.2 (br.s, 2H) FD mass spectrum [M] + 586 Example 8
【化】
実施例7において(2,3−ジヒドロ−5−ヒ
ドロキシ−2,4,6,7−テトラメチル−1−
ベンゾフラン−2−イル)メタノール1mmolの
代りに2−(2,3−ジヒドロ−5−ヒドロキシ
−2,4,6,7−テトラメチル−1−ベンゾフ
ラン−2−イル)エタノール1mmolを用いた以
外は実施例7と同様に反応及び分離精製を行なう
ことにより、下記の物性を有するジ〔2−(2,
3−ジヒドロ−5−ヒドロキシ−2,4,6,7
−テトラメチル−1−ベンゾフラン−2−イル)
エチル〕3,3′−チオジプロピオネート〔化合物
(10)〕を0.24g得た。
NMRスペクトル(90MHz)δHMS CDCl3:
1.38(s,6H);2.03(br.s,22H);
2.35〜3.1(m,12H);4.2(t,J=7Hz,
4H);
4.25(br.s,2H)
FD質量スペクトル
〔M〕+614
実施例 9〜12In Example 7, (2,3-dihydro-5-hydroxy-2,4,6,7-tetramethyl-1-
Except that 1 mmol of 2-(2,3-dihydro-5-hydroxy-2,4,6,7-tetramethyl-1-benzofuran-2-yl)ethanol was used instead of 1 mmol of benzofuran-2-yl)methanol. By carrying out the reaction and separation and purification in the same manner as in Example 7, di[2-(2,
3-dihydro-5-hydroxy-2,4,6,7
-tetramethyl-1-benzofuran-2-yl)
Ethyl] 3,3'-thiodipropionate [compound
(10)] was obtained. NMR spectrum (90MHz) δ HMS CDCl3 : 1.38 (s, 6H); 2.03 (br.s, 22H); 2.35-3.1 (m, 12H); 4.2 (t, J=7Hz,
4H); 4.25 (br.s, 2H) FD mass spectrum [M] + 614 Examples 9-12
【化】
実施例7において(2,3−ジヒドロ−5−ヒ
ドロキシ−2,4,6,7−テトラメチル−1−
ベンゾフラン−2−イル)メタノール1mmolの
代りに(2,3−ジヒドロ−5−ヒドロキシ−
4,6,7−トリメチル−1−ベンゾフラン−2
−イル)メタノール、2−(2,3−ジヒドロ−
5−ヒドロキシ−4,6,7−トリメチル−1−
ベンゾフラン−2−イル)エタノール、3−(2,
3−ジヒドロ−5−ヒドロキシ−4,6,7−ト
リメチル−1−ベンゾフラン−2−イル)プロパ
ノール又は3−(2,3−ジヒドロ−5−ヒドロ
キシ−2,4,6,7−テトラメチル−1−ベン
ゾフラン−2−イル)プロパノールをそれぞれ
1mmol用いた以外は実施例7と同様に反応及び
分離精製を行なうことにより、それぞれ対応する
3,3′−チオジプロピオン酸ジエステルを得た。
その結果を第2表に示す。In Example 7, (2,3-dihydro-5-hydroxy-2,4,6,7-tetramethyl-1-
(2,3-dihydro-5-hydroxy-
4,6,7-trimethyl-1-benzofuran-2
-yl)methanol, 2-(2,3-dihydro-
5-hydroxy-4,6,7-trimethyl-1-
benzofuran-2-yl)ethanol, 3-(2,
3-dihydro-5-hydroxy-4,6,7-trimethyl-1-benzofuran-2-yl)propanol or 3-(2,3-dihydro-5-hydroxy-2,4,6,7-tetramethyl- 1-benzofuran-2-yl)propanol, respectively.
The corresponding 3,3'-thiodipropionic acid diesters were obtained by carrying out the reaction and separation and purification in the same manner as in Example 7, except that 1 mmol was used.
The results are shown in Table 2.
【表】 実施例 13〜15【table】 Examples 13-15
【化】[ka]
【化】
実施例7において3,3′−チオジプロピオン酸
0.5mmolの代りにコハク酸、アジピン酸又はセバ
シン酸をそれぞれ0.5mmol用いた以外は実施例7
と同様に反応及び分離精製を行なうことにより、
それぞれ対応するジエステルを得た。その結果を
第3表に示す。[Chemical formula] In Example 7, 3,3'-thiodipropionic acid
Example 7 except that 0.5 mmol of each of succinic acid, adipic acid, or sebacic acid was used instead of 0.5 mmol.
By performing the reaction and separation and purification in the same manner as
The corresponding diesters were obtained. The results are shown in Table 3.
【表】 実施例 16【table】 Example 16
【化】
窒素雰囲気下で(2,3−ジヒドロ−5−ヒド
ロキシ−2,4,6,7−テトラメチル−1−ベ
ンゾフラン−2−イル)メタノール0.222g
1mmol、3−(3,5−ジ−t−ブチル−4−ヒ
ドロキシフエニル)プロピオン酸0.278g
(1mmol)、p−トルエンスルホン酸0.01g及びト
ルエン15mlから成る混合液を加熱し、生成する水
を共沸混合物として系外へ除去した。得られた反
応液を減圧下に濃縮し、その残渣をシリカゲルカ
ラムクロマトグラフイーで精製することにより、
下記の物性を有する(2,3−ジヒドロ−5−ヒ
ドロキシ−2,4,6,7−テトラメチル−1−
ベンゾフラン−2−イル)メチル 3−(3,5
−ジ−t−ブチル−4−ヒドロキシフエニル)プ
ロピオネート〔化合物(19)〕を0.39g得た。
NMRスペクトル(90MHz)δHMS CDCl3:
1.37(s,21H);2.02(br.s,9H);
2.35〜3.1(m,6H);4.08(s,2H);4.1(br.s,
1H);
4.98(s,1H);6.91(s,2H)
FD質量スペクトル
〔M〕+482
実施例 17[Chemical formula] 0.222 g of (2,3-dihydro-5-hydroxy-2,4,6,7-tetramethyl-1-benzofuran-2-yl)methanol under nitrogen atmosphere
1 mmol, 3-(3,5-di-t-butyl-4-hydroxyphenyl)propionic acid 0.278 g
(1 mmol), 0.01 g of p-toluenesulfonic acid, and 15 ml of toluene was heated, and the water produced was removed from the system as an azeotrope. The resulting reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography.
It has the following physical properties (2,3-dihydro-5-hydroxy-2,4,6,7-tetramethyl-1-
benzofuran-2-yl)methyl 3-(3,5
0.39 g of -di-t-butyl-4-hydroxyphenyl)propionate [Compound (19)] was obtained. NMR spectrum (90MHz) δ HMS CDCl3 : 1.37 (s, 21H); 2.02 (br.s, 9H); 2.35-3.1 (m, 6H); 4.08 (s, 2H); 4.1 (br.s,
1H); 4.98 (s, 1H); 6.91 (s, 2H) FD mass spectrum [M] + 482 Example 17
【化】
実施例16において(2,3−ジヒドロ−5−ヒ
ドロキシ−2,4,6,7−テトラメチル−1−
ベンゾフラン−2−イル)メタノール1mmolの
代りに2−(2,3−ジヒドロ−5−ヒドロキシ
−2,4,6,7−テトラメチル−1−ベンゾフ
ラン−2−イル)エタノール1mmolを用いた以
外は実施例16と同様に反応及び分離精製を行なう
ことにより、下記の物性を有する2−(2,3−
ジヒドロ−5−ヒドロキシ−2,4,6,7−テ
トラメチル−1−ベンゾフラン−2−イル)エチ
ル 3−(3,5−ジ−t−ブチル−4−ヒドロ
キシフエニル)プロピオネート〔化合物(20)〕
を0.39g得た。
NMRスペクトル(90MHz)δHMS CDCl3:
1.37(s,21H);1.85〜2.2(m,11H);
2.37〜3.1(m,6H);4.2(t,J=7Hz,
2H);
4.25(br.s,1H);4.98(s,1H);6.93(s,
2H)
FD質量スペクトル
〔M〕+496
実施例 18〜20In Example 16, (2,3-dihydro-5-hydroxy-2,4,6,7-tetramethyl-1-
Except that 1 mmol of 2-(2,3-dihydro-5-hydroxy-2,4,6,7-tetramethyl-1-benzofuran-2-yl)ethanol was used instead of 1 mmol of benzofuran-2-yl)methanol. By carrying out the reaction and separation and purification in the same manner as in Example 16, 2-(2,3-
Dihydro-5-hydroxy-2,4,6,7-tetramethyl-1-benzofuran-2-yl)ethyl 3-(3,5-di-t-butyl-4-hydroxyphenyl)propionate [Compound (20 )〕
0.39g of was obtained. NMR spectrum (90MHz) δ HMS CDCl3 : 1.37 (s, 21H); 1.85-2.2 (m, 11H); 2.37-3.1 (m, 6H); 4.2 (t, J = 7Hz,
2H); 4.25 (br.s, 1H); 4.98 (s, 1H); 6.93 (s,
2H) FD mass spectrum [M] + 496 Examples 18-20
【化】
実施例16において3−(3,5−ジ−t−ブチ
ル−4−ヒドロキシフエニル)プロピオン酸
1mmolの代りにステアリン酸、3−(ドデシルチ
オ)プロピオン酸又は酢酸をそれぞれ1mmol用
いた以外は実施例16と同様に反応及び分離精製を
行なうことによりそれぞれ対応するエステルを得
た。その結果を第4表に示す。[Chemical formula] In Example 16, 3-(3,5-di-t-butyl-4-hydroxyphenyl)propionic acid
The corresponding esters were obtained by carrying out the reaction and separation and purification in the same manner as in Example 16, except that 1 mmol each of stearic acid, 3-(dodecylthio)propionic acid, or acetic acid was used instead of 1 mmol. The results are shown in Table 4.
【表】 実施例 21【table】 Example 21
【化】[ka]
【化】[ka]
【化】[ka]
本発明により提供される2,3−ジヒドロベン
ゾフラン誘導体()のいくつかは、前記の試験
例の結果から明らかなとおり、α−トコフエロー
ルをはじめとする3,4−ジヒドロベンゾピラン
誘導体に比べ優れた酸化防止作用を有しており、
酸素感性な有機材料の酸化防止剤として有用であ
る。また、2,3−ジヒドロベンゾフラン誘導体
()は酸化防止作用に由来する種々の薬理作用
を有する化合物の合成中間体としても有用であ
る。
As is clear from the results of the above test examples, some of the 2,3-dihydrobenzofuran derivatives () provided by the present invention are superior to 3,4-dihydrobenzopyran derivatives including α-tocopherol. It has antioxidant effect,
Useful as an antioxidant for oxygen-sensitive organic materials. The 2,3-dihydrobenzofuran derivative (2) is also useful as an intermediate for the synthesis of compounds having various pharmacological actions derived from antioxidant action.
Claims (1)
表わし、R2は水素原子又は式【式】で表わ される基を示し、R3は水素原子又は水酸基の保
護基を表わし、nは1〜3の整数を表わす。R4
は置換基を有していてもよいアルキル基又は式 【化】 で表わされる基を示し、mは1〜4の整数を表わ
し、Aは硫黄原子を表わし、pは0又は1の整数
を表わす。) で示される2,3−ジヒドロベンゾフラン誘導
体。[Scope of Claims] 1 General formula [formula] (wherein, R 1 represents a hydrogen atom or a lower alkyl group, R 2 represents a hydrogen atom or a group represented by the formula [formula], and R 3 represents a hydrogen atom or represents a hydroxyl group-protecting group, and n represents an integer of 1 to 3. R 4
represents an alkyl group which may have a substituent or a group represented by the formula: m represents an integer of 1 to 4, A represents a sulfur atom, p represents an integer of 0 or 1 . ) A 2,3-dihydrobenzofuran derivative represented by:
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP61234013A JPS6388173A (en) | 1986-09-30 | 1986-09-30 | 2,3-dihydrobenzofuran derivative |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP61234013A JPS6388173A (en) | 1986-09-30 | 1986-09-30 | 2,3-dihydrobenzofuran derivative |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS6388173A JPS6388173A (en) | 1988-04-19 |
JPH0572908B2 true JPH0572908B2 (en) | 1993-10-13 |
Family
ID=16964185
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP61234013A Granted JPS6388173A (en) | 1986-09-30 | 1986-09-30 | 2,3-dihydrobenzofuran derivative |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS6388173A (en) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2855341B2 (en) * | 1988-06-10 | 1999-02-10 | 武田薬品工業株式会社 | New 2-substituted coumaran derivatives |
JP2855340B2 (en) * | 1988-06-10 | 1999-02-10 | 武田薬品工業株式会社 | 2-substituted coumaran derivatives |
IT1229482B (en) * | 1988-08-01 | 1991-09-03 | Foscama Biomed Chim Farma | ACIDS (RS) 2 (2,3 DIIDRO 5 HYDROXIS 4,6,7 TRIMETHYLBENZOFURANIL) ACETIC AND 2 (2,3 DIIDRO 5 ACYLOXY 4,6,7 TRIMETHYLBENZOFURANIL) ACETIC AND THEIR ESTERS, USEFUL AS MUCOREGULATORY AND ANTI-CHEMICAL DRUGS. |
IT1231341B (en) * | 1989-08-18 | 1991-11-28 | Foscama Biomed Chim Farma | 2.3 DIHYDRO 5 BONES 4,6,7 TRIMETHYLBENZOFURANI 2 (RS) REPLACED, USEFUL AS ANTIOXIDANT DRUGS WITH MUCOREGULATING AND ANTI-CHEMICAL PROPERTIES. |
CZ309633B6 (en) * | 2019-12-04 | 2023-05-31 | Univerzita Palackého v Olomouci | Phenolic dihydrobenzofuran derivatives, medical and cosmetic preparations containing these derivatives, and their use |
-
1986
- 1986-09-30 JP JP61234013A patent/JPS6388173A/en active Granted
Also Published As
Publication number | Publication date |
---|---|
JPS6388173A (en) | 1988-04-19 |
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