JP5936287B2 - 1,3,3−トリメチル−2−(3−メチルペント−2−エン−4−イニル)シクロヘキス−1−エンを製造する方法 - Google Patents
1,3,3−トリメチル−2−(3−メチルペント−2−エン−4−イニル)シクロヘキス−1−エンを製造する方法 Download PDFInfo
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- JP5936287B2 JP5936287B2 JP2014516276A JP2014516276A JP5936287B2 JP 5936287 B2 JP5936287 B2 JP 5936287B2 JP 2014516276 A JP2014516276 A JP 2014516276A JP 2014516276 A JP2014516276 A JP 2014516276A JP 5936287 B2 JP5936287 B2 JP 5936287B2
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- ynyl
- cyclohex
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- 238000000034 method Methods 0.000 title claims description 24
- WUGFRQORLBASOM-UHFFFAOYSA-N 1,3,3-trimethyl-2-(3-methylpent-2-en-4-ynyl)cyclohexene Chemical compound C#CC(C)=CCC1=C(C)CCCC1(C)C WUGFRQORLBASOM-UHFFFAOYSA-N 0.000 title claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 52
- -1 2,6,6-trimethylcyclohex-1-enyl Chemical group 0.000 claims description 16
- 239000003054 catalyst Substances 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 7
- 150000001450 anions Chemical class 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 15
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 13
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 13
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- 235000019155 vitamin A Nutrition 0.000 description 13
- 239000011719 vitamin A Substances 0.000 description 13
- 229940045997 vitamin a Drugs 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 8
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 7
- 238000005660 chlorination reaction Methods 0.000 description 7
- WUGFRQORLBASOM-XFXZXTDPSA-N 1,3,3-trimethyl-2-[(z)-3-methylpent-2-en-4-ynyl]cyclohexene Chemical compound C#CC(/C)=C\CC1=C(C)CCCC1(C)C WUGFRQORLBASOM-XFXZXTDPSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000003342 alkenyl group Chemical group 0.000 description 6
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 6
- 235000013734 beta-carotene Nutrition 0.000 description 6
- 239000011648 beta-carotene Substances 0.000 description 6
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 6
- 229960002747 betacarotene Drugs 0.000 description 6
- FDSDTBUPSURDBL-LOFNIBRQSA-N canthaxanthin Chemical compound CC=1C(=O)CCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C(=O)CCC1(C)C FDSDTBUPSURDBL-LOFNIBRQSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000376 reactant Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- 229910004298 SiO 2 Inorganic materials 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- JKQXZKUSFCKOGQ-JLGXGRJMSA-N (3R,3'R)-beta,beta-carotene-3,3'-diol Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C[C@@H](O)CC1(C)C JKQXZKUSFCKOGQ-JLGXGRJMSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- JEBFVOLFMLUKLF-IFPLVEIFSA-N Astaxanthin Natural products CC(=C/C=C/C(=C/C=C/C1=C(C)C(=O)C(O)CC1(C)C)/C)C=CC=C(/C)C=CC=C(/C)C=CC2=C(C)C(=O)C(O)CC2(C)C JEBFVOLFMLUKLF-IFPLVEIFSA-N 0.000 description 3
- OOUTWVMJGMVRQF-DOYZGLONSA-N Phoenicoxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)C(=O)C(O)CC1(C)C)C=CC=C(/C)C=CC2=C(C)C(=O)CCC2(C)C OOUTWVMJGMVRQF-DOYZGLONSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- JKQXZKUSFCKOGQ-LQFQNGICSA-N Z-zeaxanthin Natural products C([C@H](O)CC=1C)C(C)(C)C=1C=CC(C)=CC=CC(C)=CC=CC=C(C)C=CC=C(C)C=CC1=C(C)C[C@@H](O)CC1(C)C JKQXZKUSFCKOGQ-LQFQNGICSA-N 0.000 description 3
- QOPRSMDTRDMBNK-RNUUUQFGSA-N Zeaxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCC(O)C1(C)C)C=CC=C(/C)C=CC2=C(C)CC(O)CC2(C)C QOPRSMDTRDMBNK-RNUUUQFGSA-N 0.000 description 3
- JKQXZKUSFCKOGQ-LOFNIBRQSA-N all-trans-Zeaxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2=C(C)CC(O)CC2(C)C JKQXZKUSFCKOGQ-LOFNIBRQSA-N 0.000 description 3
- 235000013793 astaxanthin Nutrition 0.000 description 3
- 239000001168 astaxanthin Substances 0.000 description 3
- MQZIGYBFDRPAKN-ZWAPEEGVSA-N astaxanthin Chemical compound C([C@H](O)C(=O)C=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C(=O)[C@@H](O)CC1(C)C MQZIGYBFDRPAKN-ZWAPEEGVSA-N 0.000 description 3
- 229940022405 astaxanthin Drugs 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 235000012682 canthaxanthin Nutrition 0.000 description 3
- 239000001659 canthaxanthin Substances 0.000 description 3
- 229940008033 canthaxanthin Drugs 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000006297 dehydration reaction Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- KBPHJBAIARWVSC-XQIHNALSSA-N trans-lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C KBPHJBAIARWVSC-XQIHNALSSA-N 0.000 description 3
- 235000010930 zeaxanthin Nutrition 0.000 description 3
- 239000001775 zeaxanthin Substances 0.000 description 3
- 229940043269 zeaxanthin Drugs 0.000 description 3
- 0 CC1(C)C(CC=C(C)C#CC(C(C)=CCOC(*)=O)=O)=C(C)CCC1 Chemical compound CC1(C)C(CC=C(C)C#CC(C(C)=CCOC(*)=O)=O)=C(C)CCC1 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
- 235000021466 carotenoid Nutrition 0.000 description 2
- 150000001747 carotenoids Chemical class 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- UNSDWONDAUAWPV-UHFFFAOYSA-N methylaluminum;oxane Chemical compound [Al]C.C1CCOCC1 UNSDWONDAUAWPV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-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
- ACLRHGVHKRXKRW-UHFFFAOYSA-N (4-chloro-3-methyl-4-oxobut-2-enyl) acetate Chemical compound CC(=O)OCC=C(C)C(Cl)=O ACLRHGVHKRXKRW-UHFFFAOYSA-N 0.000 description 1
- ZXMGHDIOOHOAAE-UHFFFAOYSA-N 1,1,1-trifluoro-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)NS(=O)(=O)C(F)(F)F ZXMGHDIOOHOAAE-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
- ZNOVTXRBGFNYRX-UHFFFAOYSA-N 2-[[4-[(2-amino-5-methyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 ZNOVTXRBGFNYRX-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- FIJNIEJPTVQKIT-UHFFFAOYSA-N CC1=C(CCC(=C)C#C)C(C)(C)CCC1 Chemical compound CC1=C(CCC(=C)C#C)C(C)(C)CCC1 FIJNIEJPTVQKIT-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- HWTAHDYIVQEYSX-UHFFFAOYSA-N [3,7-dimethyl-4-oxo-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,7-dien-5-ynyl] acetate Chemical compound CC(=O)OCC=C(C)C(=O)C#CC(C)=CCC1=C(C)CCCC1(C)C HWTAHDYIVQEYSX-UHFFFAOYSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- VMPVEPPRYRXYNP-UHFFFAOYSA-I antimony(5+);pentachloride Chemical compound Cl[Sb](Cl)(Cl)(Cl)Cl VMPVEPPRYRXYNP-UHFFFAOYSA-I 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000000010 aprotic solvent Substances 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
- 230000004097 bone metabolism Effects 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- XTEGARKTQYYJKE-UHFFFAOYSA-N chloric acid Chemical compound OCl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-N 0.000 description 1
- 229940005991 chloric acid Drugs 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 150000007944 thiolates Chemical class 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
- C07C403/24—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by six-membered non-aromatic rings, e.g. beta-carotene
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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- C07C403/02—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains containing only carbon and hydrogen atoms
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- C07C403/06—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms
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Description
は、多くの用途に重要な成分である。ビタミンAは、例えば視覚プロセス、遺伝子転写、免疫機能、骨代謝、造血、皮膚および細胞の健康ならびに抗酸化機能など、体中の様々な機能において役割を果たす。ビタミンA(およびその誘導体)が重要であること、かつその合成が複雑であることから、向上した製造方法が常に必要とされている。
の化合物は有機合成において重要な化合物である。式(I)の化合物は、例えば、ビタミンAまたはβ−カロテンの合成で使用される中間体の合成で使用される。
を脱水することによる、式(I)の化合物の製造方法が記載されている。これらの条件下にて、生成物は収率70%で得られる。1,3,3−トリメチル−2−(3−メチルペント−2−エン−4−イニル)シクロヘキス−1−エンは異性体混合物として得られ、使用される。
の化合物である、過剰量(85%を超える量)の(Z)−1,3,3−トリメチル−2−(3−メチルペント−2−エン−4−イニル)シクロヘキス−1−エンを有する、式(I)の生成物が生成されることである。
の化合物にも関する。
1H−NMR(300MHz,CDCl3):δ[ppm]=0.99(s,6H,CH3,H12+H13),1.42(m,2H,CH2,H2),1.55(m,2H,CH2,H3),1.58(s,3H,CH3,H14),1.85(s,3H,CH3,H15),1.90(t,J=6.3Hz,2H,CH2,H4),2.99(d,J=6.8Hz,2H,CH2,H7),3.16(s,1H,CH,H11),5.61(t,1H,CH,6.8Hz,H8)。
HPLC(実施例1に記載される):tR(Ia)=5.59分
TLC(SiO2,シクロヘキサン/酢酸エチル9:1,アニスアルデヒド):Rf(Ib)=0.67
の化合物である、((Z)−1,3,3−トリメチル−2−(3−メチルペント−2−エン−4−イニル)シクロヘキス−1−エン)のE型は、例えばRey et al.,Tetrahedron Letters 1993,34(39),p.6293−6296に記載の方法に従って合成することができる。式(Ib)の化合物の分析データを以下にまとめる:
1H−NMR(300MHz,CDCl3):δ[ppm]=0.96(s,6H,2×CH3,H12+H13),1.40−1.44(m,2H,CH2,H2),1.53(s,3H,CH3,H14),1.55−1.61(m,2H,CH2,H3),1.84(d,J=1.4Hz,3H,CH3,H15),1.92(t,J=6.0Hz,2H,CH2,H4),2.74(s,1H,CH,H11),2.78(d,J=6.8Hz,2H,CH2,H7),5.80(td,J=6.8Hz,J=1.4Hz,1H,CH,H8)。
HPLC(実施例1に記載される通り):tR(Ib)=5.24分
TLC(SiO2,シクロヘキサン/酢酸エチル9:1,アニスアルデヒド):Rf(Ib)=0.67。
は、ビタミンAまたはβ−カロテンまたは他のカロテノイド、例えばカンタキサンチン、アスタキサンチンおよびゼアキサンチンの合成のための、特にビタミンA(およびその誘導体)の合成のための中間体である。式(III)の化合物は新規な化合物である。
の化合物(式中、R1がC1〜C15アルキル部位またはC2〜C18アルケニル部位を示す)の塩素化によって生成することができ、少なくとも1種類の塩素化反応物が使用される。
[実施例1:(Z)−1,3,3−トリメチル−2−(3−メチルペント−2−エン−4−イニル)シクロヘキス−1−エン(式(Ia)の化合物)]
窒素雰囲気下にて、[(C5(CH3)5)RuCl(μ2−SMe)2Ru(C5(CH3)5)Cl]16.1mg(0.03mmol,5モル%)およびテトラフルオロホウ酸アンモニウム5.3mg(0.05mmol)を無水1,2−ジクロロエタン7.5mlに溶解した。その暗赤色の溶液に、無水1,2−ジクロロエタン5.0ml中の3−メチル−5−(2,6,6−トリメチルシクロヘキス−1−エニル)ペント−1−イン−3−オール(式(II)の化合物)129mg(0.5mmol)の溶液を室温にて一滴ずつ添加した。出発原料を完全に添加した後、溶液を60℃に加熱した。60℃で3時間後、茶色の溶液を室温に冷却した。
[Ia:]
1H−NMR(300MHz,CDCl3):δ[ppm]=0.99(s,6H,CH3,H12+H13),1.42(m,2H,CH2,H2),1.55(m,2H,CH2,H3),1.58(s,3H,CH3,H14),1.85(s,3H,CH3,H15),1.90(t,J=6.3Hz,2H,CH2,H4),2.99(d,J=6.8Hz,2H,CH2,H7),3.16(s,1H,CH,H11),5.61(t,1H,CH,6.8Hz,H8)。
13C−NMR(300MHz,CDCl3):δ[ppm]=19.5(C3),19.8(C14),22.7(C15),28.2(C12+C13),30.1(C7),33.0(C4),35.0(C1),39.8(C2),80.9(C11),84.9(C10),115.5(C9),128.7(C5),135.3(C6),140.3(C8)。
GC:tR(II)=9.84分,tR(Ia)=8.85分
HPLC:tR(II)=3.17分,tR(Ia)=5.59分
TLC(SiO2,シクロヘキサン/酢酸エチル9:1,アニスアルデヒド);Rf(II)=0.16,Rf(Ia)=0.63
1H−NMR(300MHz,CDCl3):δ[ppm]=0.96(s,6H,2×CH3,H12+H13),1.40−1.44(m,2H,CH2,H2),1.53(s,3H,CH3,H14),1.55−1.61(m,2H,CH2,H3),1.84(d,J=1.4Hz,3H,CH3,H15),1.92(t,J=6.0Hz,2H,CH2,H4),2.74(s,1H,CH,H11),2.78(d,J=6.8Hz,2H,CH2,H7),5.80(td,J=6.8Hz,J=1.4Hz,1H,CH,H8)。
13C−NMR(300MHz,CDCl3):δ[ppm]=17.1(C15),19.5(C3),19.8(C14),27.8(C7),28.2(2C,C12+C13),33.0(C4),34.9(C1),39.7(C2),73.1(C11),87.1(C10),115.1(C9),128.8(C5),135.2(C6),141.0(C8)。
HPLC(実施例1に記述される通り):tR(Ib)=5.24分
TLC(SiO2,シクロヘキサン/酢酸エチル9:1,アニスアルデヒド):Rf(Ib)=0.67
装置:Agilent 7890A;キャリアーガス:ヘリウム;圧力:25psi;流量:88ml/分;注入容積:1μl;インジェクター:スプリット(10:1);インジェクター温度:250℃;カラム:HP−5(5%フェニルメチルシロキサン)(30m×320μm×0.25μm);温度プログラム:50℃(2分),15℃/分,300℃(5分);検出器:FID;検出器温度:300℃。
装置:Agilent 1050;カラム:Supelcosil LC−18(250mm×4.6mm×5μm);自動サンプラー:Agilent 1100;注入容積:2μl;溶離剤:アセトニトリル/水90:10;流量:1.5ml/分;温度:23℃;検出器:可変波長検出器;検出波長:230nm。
窒素雰囲気下にて、[(C5(CH3)5)RuCl(μ2−SMe)2Ru(C5(CH3)5)Cl]16.1mg(0.03mmol,5モル%)を無水1,2−ジクロロエタン7.5mlに溶解した。その暗赤色の溶液に、無水1,2−ジクロロエタン5.0ml中の3−メチル−5−(2,6,6−トリメチルシクロヘキス−1−エニル)ペント−1−イン−3−オール(式(II)の化合物)129mg(0.5mmol)の溶液を室温にて一滴ずつ添加した。出発原料を完全に添加した後、溶液を60℃に加熱した。60℃で24時間後、茶色の溶液を室温に冷却した。
窒素雰囲気下にて、ヨウ化銅(I)59.9mg(0.308mmol)およびビス(トリフェニルホスフィン)パラジウム(II)ジクロリド[(PPh3)2PdCl2]110.3mg(0.154mmol)を100ml四つ口フラスコも添加した。23℃にて、無水THF42.0mlを添加し、黄色の懸濁液を5分間攪拌した。シリンジを使用してトリエチルアミン2.15ml(15.4mmol)を一滴ずつ添加し、オレンジ色の液体が得られた。1分以内に、4−クロロ−3−メチル−4−オキソブト−2−エニルアセテート(式(IIIa)の化合物)
3.10g(15.4mmol)を添加し、溶液が暗いオレンジ色に変化した。実施例1の反応生成物2.92g(14.0mmol)を5分間にわたって一滴ずつ添加すると、黄色の懸濁液が形成した。反応混合物を室温に冷却し、GCおよびTLCによってモニターした。23℃で2時間20分後、すべての出発原料が消費された。反応混合物を分液漏斗に移し、ジエチルエーテル80mlで希釈し、半濃縮重炭酸ナトリウム溶液(80ml)で洗浄した。層を分離し、水層をジエチルエーテル(2×75ml)で抽出した。合わせた有機層を半飽和重炭酸ナトリウム溶液80mlで洗浄し、硫酸ナトリウムで乾燥させ、乾燥状態まで濃縮した。粗生成物(式(IVa)の化合物)
が茶色のオイルとして得られ(5.44g,純度82%,収率93%)、カラムクロマトグラフィーおよび木炭処理によって精製された。
無水トルエン1.0ml中の3−メチル−5−(2,6,6−トリメチルシクロヘキス−1−エニル)ペント−1−イン−3−オール(式(II)の化合物)26mg(0.13mmol)の溶液に、Amberlyst−15 94mgを添加した。23℃で48時間攪拌した後、濾過によって酸性イオン交換樹脂を除去し、減圧下にて溶媒を蒸発させた。粗生成物のGC分析から、式(A’)の化合物65面積%が示された。生成物A’は、参照NMRデータと比較することによって同定された(G.Ohloff et al,Helvetica Chimica Acta 1976,59,1158−1168参照)。
窒素雰囲気下にて、[(C5(CH3)5)RuCl(μ2−SMe)2Ru(C5(CH3)5)Cl]54.2mg(0.085mmol,0.625モル%)およびテトラフルオロホウ酸アンモニウム143.3mg(1.367mmol,10モル%)を無水1,2−ジクロロエタン80mlに溶解した。その暗赤色の溶液に、無水1,2−ジクロロエタン5.0ml中の3−メチル−5−(2,6,6−トリメチルシクロヘキス−1−エニル)ペント−1−イン−3−オール(式(II)の化合物)3.369g(13.67mmol)の溶液を室温にて一滴ずつ添加した。出発原料を完全に添加した後、溶液を60℃に加熱した。60℃で3時間後、茶色の溶液を室温に冷却した。半濃縮ブライン(3×150ml)で反応混合物を洗浄した。ジクロロメタン150mlで水層を2回抽出した。合わせた有機層を硫酸ナトリウムで乾燥させ、乾燥状態まで濃縮した。不要な副生成物として収率15%の1,3,3−トリメチル−2−(3−メチレンペント−4−イニル)シクロヘキス−1エン(式(VI)の化合物)と共に、Z/E比94:6を有する粗生成物(式(I)の化合物)が収率81%で得られた。
Claims (7)
- 40〜100℃の温度で行われる、請求項1に記載の方法。
- 50〜80℃の温度で行われる、請求項1に記載の方法。
- 周囲圧力にて行われる、請求項1〜3のいずれか一項に記載の方法。
- 触媒システムとして、チオレート架橋ジルテニウム錯体、任意選択で弱配位性アニオンを使用して行われる、請求項1〜4のいずれか一項に記載の方法。
- 触媒システムとして、[(C5(CH3)5)RuCl(μ2−SMe)2Ru(C5(CH3)5)Cl]およびテトラフルオロホウ酸アンモニウムを使用して行われる、請求項1〜5のいずれか一項に記載の方法。
- 水を含有しない溶媒(または溶媒の混合物)中で行われる、請求項1〜6のいずれか一項に記載の方法。
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