JP4324670B2 - Method for producing cyclized compound - Google Patents
Method for producing cyclized compound Download PDFInfo
- Publication number
- JP4324670B2 JP4324670B2 JP2004017633A JP2004017633A JP4324670B2 JP 4324670 B2 JP4324670 B2 JP 4324670B2 JP 2004017633 A JP2004017633 A JP 2004017633A JP 2004017633 A JP2004017633 A JP 2004017633A JP 4324670 B2 JP4324670 B2 JP 4324670B2
- Authority
- JP
- Japan
- Prior art keywords
- reaction
- dione
- producing
- carbon dioxide
- cyclized compound
- 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
- 150000001875 compounds Chemical class 0.000 title claims description 90
- 238000004519 manufacturing process Methods 0.000 title claims description 49
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 128
- 238000006243 chemical reaction Methods 0.000 claims description 81
- 239000001569 carbon dioxide Substances 0.000 claims description 64
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 64
- 150000002576 ketones Chemical class 0.000 claims description 29
- -1 cyclopentadione Chemical group 0.000 claims description 23
- 239000000758 substrate Substances 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 19
- 238000007363 ring formation reaction Methods 0.000 claims description 19
- 238000003786 synthesis reaction Methods 0.000 claims description 15
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclo-pentanone Natural products O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 claims description 14
- 239000003960 organic solvent Substances 0.000 claims description 13
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- 230000015572 biosynthetic process Effects 0.000 claims description 10
- 238000006482 condensation reaction Methods 0.000 claims description 9
- 150000001923 cyclic compounds Chemical class 0.000 claims description 9
- VSGJHHIAMHUZKF-UHFFFAOYSA-N 2-methylcyclohexane-1,3-dione Chemical group CC1C(=O)CCCC1=O VSGJHHIAMHUZKF-UHFFFAOYSA-N 0.000 claims description 8
- 238000007011 Robinson annulation reaction Methods 0.000 claims description 8
- FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 claims description 8
- KLTVSWGXIAYTHO-UHFFFAOYSA-N 1-Octen-3-one Chemical compound CCCCCC(=O)C=C KLTVSWGXIAYTHO-UHFFFAOYSA-N 0.000 claims description 6
- ZIXLDMFVRPABBX-UHFFFAOYSA-N 2-methylcyclopentan-1-one Chemical compound CC1CCCC1=O ZIXLDMFVRPABBX-UHFFFAOYSA-N 0.000 claims description 6
- FEWIGMWODIRUJM-UHFFFAOYSA-N 4-hexen-3-one Chemical compound CCC(=O)C=CC FEWIGMWODIRUJM-UHFFFAOYSA-N 0.000 claims description 6
- ZPGYUDWZVQOWNY-UHFFFAOYSA-N hept-4-en-3-one Chemical compound CCC=CC(=O)CC ZPGYUDWZVQOWNY-UHFFFAOYSA-N 0.000 claims description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 5
- FDMAFOTXGNYBFG-UHFFFAOYSA-N 2-methylcycloheptan-1-one Chemical compound CC1CCCCCC1=O FDMAFOTXGNYBFG-UHFFFAOYSA-N 0.000 claims description 5
- JHHZQADGLDKIPM-UHFFFAOYSA-N hept-3-en-2-one Chemical compound CCCC=CC(C)=O JHHZQADGLDKIPM-UHFFFAOYSA-N 0.000 claims description 5
- JTHNLKXLWOXOQK-UHFFFAOYSA-N hex-1-en-3-one Chemical compound CCCC(=O)C=C JTHNLKXLWOXOQK-UHFFFAOYSA-N 0.000 claims description 5
- JLIDVCMBCGBIEY-UHFFFAOYSA-N 1-penten-3-one Chemical compound CCC(=O)C=C JLIDVCMBCGBIEY-UHFFFAOYSA-N 0.000 claims description 4
- QQZOPKMRPOGIEB-UHFFFAOYSA-N 2-Oxohexane Chemical compound CCCCC(C)=O QQZOPKMRPOGIEB-UHFFFAOYSA-N 0.000 claims description 4
- VGVHNLRUAMRIEW-UHFFFAOYSA-N 4-methylcyclohexan-1-one Chemical compound CC1CCC(=O)CC1 VGVHNLRUAMRIEW-UHFFFAOYSA-N 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- CATSNJVOTSVZJV-UHFFFAOYSA-N heptan-2-one Chemical compound CCCCCC(C)=O CATSNJVOTSVZJV-UHFFFAOYSA-N 0.000 claims description 4
- NGAZZOYFWWSOGK-UHFFFAOYSA-N heptan-3-one Chemical compound CCCCC(=O)CC NGAZZOYFWWSOGK-UHFFFAOYSA-N 0.000 claims description 4
- XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 claims description 4
- 239000012429 reaction media Substances 0.000 claims description 4
- 150000003431 steroids Chemical class 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- LABTWGUMFABVFG-ONEGZZNKSA-N (3E)-pent-3-en-2-one Chemical compound C\C=C\C(C)=O LABTWGUMFABVFG-ONEGZZNKSA-N 0.000 claims description 3
- FEWIGMWODIRUJM-HWKANZROSA-N (E)-4-hexen-3-one Chemical compound CCC(=O)\C=C\C FEWIGMWODIRUJM-HWKANZROSA-N 0.000 claims description 3
- 239000001764 (E)-oct-3-en-2-one Substances 0.000 claims description 3
- LPCWMYHBLXLJJQ-SNAWJCMRSA-N (e)-hex-3-en-2-one Chemical compound CC\C=C\C(C)=O LPCWMYHBLXLJJQ-SNAWJCMRSA-N 0.000 claims description 3
- OYLCUJRJCUXQBQ-UHFFFAOYSA-N 1-hepten-3-one Chemical compound CCCCC(=O)C=C OYLCUJRJCUXQBQ-UHFFFAOYSA-N 0.000 claims description 3
- LVGUHATVVHIJET-UHFFFAOYSA-N 1-phenylpent-1-en-3-one Chemical compound CCC(=O)C=CC1=CC=CC=C1 LVGUHATVVHIJET-UHFFFAOYSA-N 0.000 claims description 3
- LFSAPCRASZRSKS-UHFFFAOYSA-N 2-methylcyclohexan-1-one Chemical compound CC1CCCCC1=O LFSAPCRASZRSKS-UHFFFAOYSA-N 0.000 claims description 3
- JHHZQADGLDKIPM-AATRIKPKSA-N 3-Hepten-2-one Chemical compound CCC\C=C\C(C)=O JHHZQADGLDKIPM-AATRIKPKSA-N 0.000 claims description 3
- LPCWMYHBLXLJJQ-UHFFFAOYSA-N 3-Hexen-2-on Natural products CCC=CC(C)=O LPCWMYHBLXLJJQ-UHFFFAOYSA-N 0.000 claims description 3
- ZCFOBLITZWHNNC-VOTSOKGWSA-N 3-Octen-2-one Chemical compound CCCC\C=C\C(C)=O ZCFOBLITZWHNNC-VOTSOKGWSA-N 0.000 claims description 3
- ZCFOBLITZWHNNC-UHFFFAOYSA-N 3-Octen-2-one Natural products CCCCC=CC(C)=O ZCFOBLITZWHNNC-UHFFFAOYSA-N 0.000 claims description 3
- JPTOCTSNXXKSSN-VOTSOKGWSA-N 4-Octen-3-one Chemical compound CCC\C=C\C(=O)CC JPTOCTSNXXKSSN-VOTSOKGWSA-N 0.000 claims description 3
- 150000003997 cyclic ketones Chemical group 0.000 claims description 3
- CGZZMOTZOONQIA-UHFFFAOYSA-N cycloheptanone Chemical compound O=C1CCCCCC1 CGZZMOTZOONQIA-UHFFFAOYSA-N 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- JPTOCTSNXXKSSN-UHFFFAOYSA-N methylheptenone Chemical compound CCCC=CC(=O)CC JPTOCTSNXXKSSN-UHFFFAOYSA-N 0.000 claims description 3
- QVJOMQRREBIZOD-UHFFFAOYSA-N non-4-en-3-one Chemical compound CCCCC=CC(=O)CC QVJOMQRREBIZOD-UHFFFAOYSA-N 0.000 claims description 3
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052724 xenon Inorganic materials 0.000 claims description 3
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 claims description 3
- ZPGYUDWZVQOWNY-AATRIKPKSA-N (e)-hept-4-en-3-one Chemical compound CC\C=C\C(=O)CC ZPGYUDWZVQOWNY-AATRIKPKSA-N 0.000 claims description 2
- SEVSRVAJBFYTEX-FNORWQNLSA-N (e)-oct-5-en-4-one Chemical compound CCCC(=O)\C=C\CC SEVSRVAJBFYTEX-FNORWQNLSA-N 0.000 claims description 2
- BLGYEIQDYOCKAQ-UHFFFAOYSA-N 1,3-diphenylpentan-2-one Chemical compound C=1C=CC=CC=1C(CC)C(=O)CC1=CC=CC=C1 BLGYEIQDYOCKAQ-UHFFFAOYSA-N 0.000 claims description 2
- VHRGUJICHLPTDW-UHFFFAOYSA-N 2-phenylcyclopent-2-en-1-one Chemical compound O=C1CCC=C1C1=CC=CC=C1 VHRGUJICHLPTDW-UHFFFAOYSA-N 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 238000011437 continuous method Methods 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- HJSLFCCWAKVHIW-UHFFFAOYSA-N cyclohexane-1,3-dione Chemical compound O=C1CCCC(=O)C1 HJSLFCCWAKVHIW-UHFFFAOYSA-N 0.000 claims description 2
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 2
- BGTOWKSIORTVQH-HOSYLAQJSA-N cyclopentanone Chemical group O=[13C]1CCCC1 BGTOWKSIORTVQH-HOSYLAQJSA-N 0.000 claims description 2
- MWVFCEVNXHTDNF-UHFFFAOYSA-N hexanedione Natural products CCCC(=O)C(C)=O MWVFCEVNXHTDNF-UHFFFAOYSA-N 0.000 claims description 2
- YIYBQIKDCADOSF-UHFFFAOYSA-N pentenoic acid group Chemical group C(C=CCC)(=O)O YIYBQIKDCADOSF-UHFFFAOYSA-N 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- SLOCIJOTBVAMAJ-UHFFFAOYSA-N cycloheptane-1,2-dione Chemical compound O=C1CCCCCC1=O SLOCIJOTBVAMAJ-UHFFFAOYSA-N 0.000 claims 2
- TXVAOITYBBWKMG-UHFFFAOYSA-N hept-2-en-4-one Chemical compound CCCC(=O)C=CC TXVAOITYBBWKMG-UHFFFAOYSA-N 0.000 claims 1
- UCUUFSAXZMGPGH-UHFFFAOYSA-N penta-1,4-dien-3-one Chemical compound C=CC(=O)C=C UCUUFSAXZMGPGH-UHFFFAOYSA-N 0.000 description 17
- 230000035484 reaction time Effects 0.000 description 12
- 239000000047 product Substances 0.000 description 8
- 239000002699 waste material Substances 0.000 description 7
- DNHDRUMZDHWHKG-UHFFFAOYSA-N wieland–miescher ketone Chemical compound C1CC(=O)C=C2CCCC(=O)C21C DNHDRUMZDHWHKG-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 239000002351 wastewater Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 150000002894 organic compounds Chemical class 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- 125000005594 diketone group Chemical group 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- TXVAOITYBBWKMG-HWKANZROSA-N 2-hepten-4-one Chemical compound CCCC(=O)\C=C\C TXVAOITYBBWKMG-HWKANZROSA-N 0.000 description 2
- UJBOOUHRTQVGRU-UHFFFAOYSA-N 3-methylcyclohexan-1-one Chemical compound CC1CCCC(=O)C1 UJBOOUHRTQVGRU-UHFFFAOYSA-N 0.000 description 2
- RHLVCLIPMVJYKS-UHFFFAOYSA-N 3-octanone Chemical compound CCCCCC(=O)CC RHLVCLIPMVJYKS-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- LOGSONSNCYTHPS-UHFFFAOYSA-N cyclopentane-1,3-dione Chemical compound O=C1CCC(=O)C1 LOGSONSNCYTHPS-UHFFFAOYSA-N 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 238000005580 one pot reaction Methods 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- ULPMRIXXHGUZFA-UHFFFAOYSA-N (R)-4-Methyl-3-hexanone Natural products CCC(C)C(=O)CC ULPMRIXXHGUZFA-UHFFFAOYSA-N 0.000 description 1
- VAIFYHGFLAPCON-UHFFFAOYSA-N 1,3-Diacetylpropane Chemical compound CC(=O)CCCC(C)=O VAIFYHGFLAPCON-UHFFFAOYSA-N 0.000 description 1
- HCXJQYYBWZTKMB-UHFFFAOYSA-N 2,3,4,7,8,8a-hexahydroisoquinoline-1,6-dione Chemical compound O=C1NCCC2=CC(CCC12)=O HCXJQYYBWZTKMB-UHFFFAOYSA-N 0.000 description 1
- CIISROPQPGGRTG-UHFFFAOYSA-N 2,5-diethylcyclopentan-1-one Chemical compound CCC1CCC(CC)C1=O CIISROPQPGGRTG-UHFFFAOYSA-N 0.000 description 1
- MKLARKDYEBNZFK-UHFFFAOYSA-N 2,5-dimethylcyclopentan-1-one Chemical compound CC1CCC(C)C1=O MKLARKDYEBNZFK-UHFFFAOYSA-N 0.000 description 1
- OJVAMHKKJGICOG-UHFFFAOYSA-N 2,5-hexanedione Chemical compound CC(=O)CCC(C)=O OJVAMHKKJGICOG-UHFFFAOYSA-N 0.000 description 1
- CATGMLRVPMQRJQ-UHFFFAOYSA-N 2,6-diethylcyclohexan-1-one Chemical compound CCC1CCCC(CC)C1=O CATGMLRVPMQRJQ-UHFFFAOYSA-N 0.000 description 1
- AILVYPLQKCQNJC-UHFFFAOYSA-N 2,6-dimethylcyclohexan-1-one Chemical compound CC1CCCC(C)C1=O AILVYPLQKCQNJC-UHFFFAOYSA-N 0.000 description 1
- BZIBDUSNXGEVLS-UHFFFAOYSA-N 2,7-diethylcycloheptan-1-one Chemical compound C(C)C1C(C(CCCC1)CC)=O BZIBDUSNXGEVLS-UHFFFAOYSA-N 0.000 description 1
- JEEQHJDSYXNZDE-UHFFFAOYSA-N 2,7-dimethylcycloheptan-1-one Chemical compound CC1CCCCC(C)C1=O JEEQHJDSYXNZDE-UHFFFAOYSA-N 0.000 description 1
- NAFAJFUPGSGMJP-UHFFFAOYSA-N 2-ethylcycloheptan-1-one Chemical compound CCC1CCCCCC1=O NAFAJFUPGSGMJP-UHFFFAOYSA-N 0.000 description 1
- WKYYYUWKFPFVEY-UHFFFAOYSA-N 2-ethylcyclohexan-1-one Chemical compound CCC1CCCCC1=O WKYYYUWKFPFVEY-UHFFFAOYSA-N 0.000 description 1
- HNFOYUZUPUVFDP-UHFFFAOYSA-N 2-ethylcyclooctan-1-one Chemical compound CCC1CCCCCCC1=O HNFOYUZUPUVFDP-UHFFFAOYSA-N 0.000 description 1
- PPTKUTYPOKHBTL-UHFFFAOYSA-N 2-ethylcyclopentan-1-one Chemical compound CCC1CCCC1=O PPTKUTYPOKHBTL-UHFFFAOYSA-N 0.000 description 1
- MJFJFHJQZCMMKL-UHFFFAOYSA-N 2-methylcyclooctan-1-one Chemical compound CC1CCCCCCC1=O MJFJFHJQZCMMKL-UHFFFAOYSA-N 0.000 description 1
- IEVRHAUJJJBXFH-UHFFFAOYSA-N 3-ethylcyclohexan-1-one Chemical compound CCC1CCCC(=O)C1 IEVRHAUJJJBXFH-UHFFFAOYSA-N 0.000 description 1
- DAHXJQBIVWXDAZ-UHFFFAOYSA-N 3-ethylcyclooctan-1-one Chemical compound CCC1CCCCCC(=O)C1 DAHXJQBIVWXDAZ-UHFFFAOYSA-N 0.000 description 1
- PFCHFHIRKBAQGU-UHFFFAOYSA-N 3-hexanone Chemical compound CCCC(=O)CC PFCHFHIRKBAQGU-UHFFFAOYSA-N 0.000 description 1
- GSYFDULLCGVSNJ-UHFFFAOYSA-N 3-methylcycloheptan-1-one Chemical compound CC1CCCCC(=O)C1 GSYFDULLCGVSNJ-UHFFFAOYSA-N 0.000 description 1
- HNEQUAAFVQKBFI-UHFFFAOYSA-N 3-methylcyclooctan-1-one Chemical compound CC1CCCCCC(=O)C1 HNEQUAAFVQKBFI-UHFFFAOYSA-N 0.000 description 1
- AOKRXIIIYJGNNU-UHFFFAOYSA-N 3-methylcyclopentan-1-one Chemical compound CC1CCC(=O)C1 AOKRXIIIYJGNNU-UHFFFAOYSA-N 0.000 description 1
- KURXRTNJIITRCV-UHFFFAOYSA-N 4-ethylcycloheptan-1-one Chemical compound CCC1CCCC(=O)CC1 KURXRTNJIITRCV-UHFFFAOYSA-N 0.000 description 1
- OKSDJGWHKXFVME-UHFFFAOYSA-N 4-ethylcyclohexan-1-one Chemical compound CCC1CCC(=O)CC1 OKSDJGWHKXFVME-UHFFFAOYSA-N 0.000 description 1
- UOUGRVQDOAJZRF-UHFFFAOYSA-N 4-ethylcyclooctan-1-one Chemical compound CCC1CCCCC(=O)CC1 UOUGRVQDOAJZRF-UHFFFAOYSA-N 0.000 description 1
- WXVNSHRGPVHBPD-UHFFFAOYSA-N 4-methylcycloheptan-1-one Chemical compound CC1CCCC(=O)CC1 WXVNSHRGPVHBPD-UHFFFAOYSA-N 0.000 description 1
- ZFWLQRVURWYIME-UHFFFAOYSA-N 4-methylcyclooctan-1-one Chemical compound CC1CCCCC(=O)CC1 ZFWLQRVURWYIME-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ODTXFSDIJUUWFP-UHFFFAOYSA-N CC(CCCCCC)=O.CCCC(CCC)=O Chemical compound CC(CCCCCC)=O.CCCC(CCC)=O ODTXFSDIJUUWFP-UHFFFAOYSA-N 0.000 description 1
- HUSMIWYZTJTCTK-UHFFFAOYSA-N CC1=CC=C(C=C1)C(=O)C(CCC(=O)C)C#N Chemical compound CC1=CC=C(C=C1)C(=O)C(CCC(=O)C)C#N HUSMIWYZTJTCTK-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 238000006957 Michael reaction Methods 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 1
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 1
- 238000005575 aldol reaction Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000008365 aromatic ketones Chemical class 0.000 description 1
- 125000003609 aryl vinyl group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- IIRFCWANHMSDCG-UHFFFAOYSA-N cyclooctanone Chemical compound O=C1CCCCCCC1 IIRFCWANHMSDCG-UHFFFAOYSA-N 0.000 description 1
- CIISBNCSMVCNIP-UHFFFAOYSA-N cyclopentane-1,2-dione Chemical compound O=C1CCCC1=O CIISBNCSMVCNIP-UHFFFAOYSA-N 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- UHKZGSSYNVLIHY-UHFFFAOYSA-N ethyl 1-benzyl-2,4-dioxopiperidine-3-carboxylate Chemical compound O=C1C(C(=O)OCC)C(=O)CCN1CC1=CC=CC=C1 UHKZGSSYNVLIHY-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 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
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 229910052743 krypton Inorganic materials 0.000 description 1
- DNNSSWSSYDEUBZ-UHFFFAOYSA-N krypton atom Chemical compound [Kr] DNNSSWSSYDEUBZ-UHFFFAOYSA-N 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 229940051960 magnesium oxide 50 mg Drugs 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- MQWCXKGKQLNYQG-UHFFFAOYSA-N methyl cyclohexan-4-ol Natural products CC1CCC(O)CC1 MQWCXKGKQLNYQG-UHFFFAOYSA-N 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- 229910052754 neon Inorganic materials 0.000 description 1
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- SEVSRVAJBFYTEX-UHFFFAOYSA-N oct-5-en-4-one Chemical compound CCCC(=O)C=CCC SEVSRVAJBFYTEX-UHFFFAOYSA-N 0.000 description 1
- YWXLSHOWXZUMSR-UHFFFAOYSA-N octan-4-one Chemical compound CCCCC(=O)CCC YWXLSHOWXZUMSR-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- HTSABYAWKQAHBT-UHFFFAOYSA-N trans 3-methylcyclohexanol Natural products CC1CCCC(O)C1 HTSABYAWKQAHBT-UHFFFAOYSA-N 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
- Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本発明は、二酸化炭素の存在下に、ケトン（以下、ケトン類と記載することがある）とビニルケトン（以下、ビニルケトン類と記載することがある）とを反応基質として、環化反応又は縮環反応を遂行させる、環化化合物の製造方法に関するものであり、更に詳しくは、二酸化炭素の存在下、即ち、超臨界二酸化炭素、亜臨界二酸化炭素ないし加圧二酸化炭素を反応媒体とすることで、有機溶媒を用いることなく、従来の方法に比べ、短い反応時間で環化化合物を、選択的に製造する方法に関するものである。
本発明は、環境問題等を抜本的に解消することが可能な、次世代の化学合成技術としてその実用化が強く期待されている、超臨界流体、亜臨界流体等の加圧媒体を利用した有機化合物の合成技術の分野において、二酸化炭素の存在下に反応基質を反応させることにより、環化化合物を短時間で合成することを可能にし、更に、環化化合物の選択的合成を可能にし、副反応生成物の含有量が少ない環化化合物を大量に製造することを可能にする新規環化化合物の製造方法を提供するものである。本発明は、環境にやさしい、新規な環化化合物の製造方法を提供するものとして有用である。
尚、本発明において、ケトンとはケトン化合物の範囲内の化合物、ビニルケトンとはビニルケトン化合物の範囲内の化合物を指し、それぞれ、ケトン以外の化合物、ビニルケトン以外の化合物は含まない。このことを前提として、本明細書では、これらの化合物を、それぞれケトン類、ビニルケトン類と記載することがある。
In the present invention, in the presence of carbon dioxide, a cyclization reaction or a condensed ring is carried out using a ketone (hereinafter sometimes referred to as a ketone) and a vinyl ketone (hereinafter sometimes referred to as a vinyl ketone) as a reaction substrate. The present invention relates to a method for producing a cyclized compound, and more specifically, in the presence of carbon dioxide, that is, by using supercritical carbon dioxide, subcritical carbon dioxide or pressurized carbon dioxide as a reaction medium, The present invention relates to a method for selectively producing a cyclized compound in a shorter reaction time without using an organic solvent as compared with a conventional method.
The present invention utilizes a pressurized medium such as a supercritical fluid and a subcritical fluid, which is expected to be practically used as a next-generation chemical synthesis technology capable of drastically solving environmental problems and the like. In the field of organic compound synthesis technology, by reacting a reaction substrate in the presence of carbon dioxide, it becomes possible to synthesize a cyclized compound in a short time, and further enable selective synthesis of the cyclized compound. The present invention provides a method for producing a novel cyclized compound that makes it possible to produce a large amount of a cyclized compound having a low content of side reaction products. The present invention is useful for providing an environmentally friendly method for producing a novel cyclized compound.
In the present invention, ketone refers to a compound within the range of a ketone compound, and vinyl ketone refers to a compound within the range of a vinyl ketone compound, and does not include compounds other than ketones and compounds other than vinyl ketones. Based on this premise, in the present specification, these compounds are sometimes referred to as ketones and vinyl ketones, respectively.
従来から、縮環化合物ないし環化化合物の製造には、ロビンソン反応を利用する方法が有効であることが知られている。これは、ケトンとビニルケトンとの反応であり、この反応は、初めに、マイケル反応が起こり、続いてアルドール反応、そして、最後に脱水反応を経由する反応である。縮環化合物ないし環化化合物を製造する場合、従来の技術として、数多くの論文、特許が発表されている。先行技術文献では、例えば、ビフェニル誘導体として、４‘−メチルベンゾイル酢酸エチルエステルから２−（（４−メチルフェニル）カルボニル）−５−オキソヘキサンニトリル等を製造する方法が提案されている（特許文献１参照）。この製造方法では、初めはエタノールを有機溶媒として使用し、次に、トルエンを反応溶媒として用い、抽出精製操作を行なっている。また、１−ベンジル−３−カルボエトキシ−２，４−ピペリジンジオンから、初めはｔｅｒｔ−ブタノールを、次にベンゼンを反応溶媒として、更に、抽出精製過程を経て２−ベンジル−８ａ−カルボエトキシ−１，６−ジオキソ−１，２，３，４，６，７，８，８ａ−オクタヒドロイソキノリンを製造する方法が提案されている（特許文献２参照）。この様に、ロビンソン反応を利用した環化化合物の製造には、その多くは有機溶媒を用いており、また、無溶媒で製造を行なっている場合もあるが、いずれの場合にも選択性が悪いのが現状である。 Conventionally, it is known that a method using a Robinson reaction is effective for the production of a condensed ring compound or a cyclized compound. This is a reaction between a ketone and vinyl ketone, and this reaction is a reaction in which a Michael reaction occurs first, followed by an aldol reaction, and finally a dehydration reaction. When producing a condensed ring compound or a cyclized compound, many papers and patents have been published as conventional techniques. In the prior art literature, for example, a method for producing 2-((4-methylphenyl) carbonyl) -5-oxohexanenitrile from 4′-methylbenzoylacetic acid ethyl ester as a biphenyl derivative has been proposed (Patent Literature). 1). In this production method, ethanol is first used as an organic solvent, and then toluene is used as a reaction solvent to perform extraction and purification operations. Further, from 1-benzyl-3-carboethoxy-2,4-piperidinedione, first, tert-butanol and then benzene as a reaction solvent, and further through an extraction purification process, 2-benzyl-8a-carboethoxy- A method for producing 1,6-dioxo-1,2,3,4,6,7,8,8a-octahydroisoquinoline has been proposed (see Patent Document 2). As described above, in the production of cyclized compounds utilizing the Robinson reaction, most of them use an organic solvent, and there are cases where the production is carried out without a solvent. The current situation is bad.
超臨界二酸化炭素を用いた反応は、近年、論文、特許出願件数ともに大幅に増大している。特に、二酸化炭素を超臨界状態で使用することで、反応時間、反応収率が大幅に改善されるため、それを反応溶媒としての利用が非常に注目される。また、二酸化炭素が、安全、無害、安価、かつ大量に存在する物質であることから、二酸化炭素の利用技術を、環境調和型製造技術として利用することも注目されている。 In recent years, the number of papers and patent applications has greatly increased in reactions using supercritical carbon dioxide. In particular, when carbon dioxide is used in a supercritical state, the reaction time and the reaction yield are greatly improved. In addition, since carbon dioxide is a safe, harmless, inexpensive, and abundant substance, it is also drawing attention that carbon dioxide utilization technology is used as an environmentally conscious manufacturing technology.
このような状況の中で、本発明者らは、上記従来技術に鑑みて、簡単な合成プロセスで、環化化合物を高い選択性で、収率良く製造することができ、しかも、環境問題を解決できる新しい有機化合物の製造方法を開発することを目標として、鋭意研究を積み重ねた結果、超臨界二酸化炭素、亜臨界二酸化炭素又は加圧二酸化炭素を反応溶媒とし、ケトン類とビニルケトン類とを反応基質として、環化反応又は縮環反応を進行させることにより、有機溶媒を用いない、環境にやさしい、環化化合物の製造方法を開発すると同時に、従来に比べて、短時間でロビンソン反応による環化化合物を製造することが可能になることを見出し、本発明を完成するに至った。
即ち、本発明の目的は、有機溶媒、酸、アルカリ等を極力使用せずに反応を遂行し、環化化合物を、効率良く、環境にやさしく製造する方法を提供することである。
また、本発明の目的は、反応時間５分〜２４時間という、従来の１日以上かかっていた反応時間に比べて、極めて短時間で、複雑な環化又は縮環反応を遂行することが可能であり、かつ、抽出分離操作も容易になり、処理操作も更に簡便にすることが可能な、環化化合物の製造方法を提供するものである。
また、本発明の目的は、高い化合物の選択性、高収率を有する、環化化合物の製造方法を提供することである。
また、本発明の目的は、廃水、廃物がほとんど発生しない製造方法であって、廃水、廃物の処理をほとんど必要としない、環境にやさしい、環化化合物の製造方法を提供することである。
Under such circumstances, the present inventors have been able to produce a cyclized compound with high selectivity and high yield by a simple synthesis process in view of the above-described conventional technology, and also have an environmental problem. As a result of intensive research with the goal of developing a new method for producing organic compounds that can be solved, the reaction of ketones and vinyl ketones using supercritical carbon dioxide, subcritical carbon dioxide, or pressurized carbon dioxide as a reaction solvent By developing a cyclization reaction or condensation reaction as a substrate, we developed a method for producing cyclized compounds that do not use organic solvents and are friendly to the environment. At the same time, cyclization by the Robinson reaction takes less time than conventional methods. The inventors have found that it is possible to produce a compound, and have completed the present invention.
That is, an object of the present invention is to provide a method for producing a cyclized compound efficiently and environmentally by carrying out the reaction without using an organic solvent, acid, alkali or the like as much as possible.
In addition, the object of the present invention is to carry out complex cyclization or condensation reaction in a very short time compared with the reaction time of 5 minutes to 24 hours, which conventionally takes 1 day or more. In addition, the present invention provides a method for producing a cyclized compound, which facilitates the extraction and separation operation and further simplifies the treatment operation.
Another object of the present invention is to provide a method for producing a cyclized compound having high compound selectivity and high yield.
Another object of the present invention is to provide an environmentally friendly method for producing a cyclized compound that is a production method that hardly generates waste water and waste, and that requires little treatment of waste water and waste.
上記課題を解決するための本発明は、以下の技術的手段から構成される。
（１）超臨界二酸化炭素、亜臨界二酸化炭素ないし加圧二酸化炭素を反応媒体とし、有機溶媒を用いることなく、ケトンとビニルケトンとを反応基質として、反応温度・反応圧力を選択し、圧力を変化させることなく、一段階反応で、環化反応又は縮環反応させることにより、環状ケトン構造を有する環化化合物を合成することを特徴とする環化化合物の製造方法。
（２）二酸化炭素が、圧力７．３ＭＰａ〜５０ＭＰａ、温度３１℃〜３００℃の二酸化炭素であることを特徴とする上記（１）に記載の環化化合物の製造方法。
（３）ケトンが、一般式（１）
The present invention for solving the above-described problems comprises the following technical means.
(1) a supercritical carbon dioxide, subcritical carbon dioxide or pressurized carbon dioxide reaction medium, without using an organic solvent, a ketone and Biniruketo in as reaction substrate, and selecting the reaction temperature and reaction pressure, the pressure without changing the, in a single step reaction, by cyclization reaction or a condensed reaction method of cyclic compounds, characterized by synthesis of cyclized compound having a cyclic ketone structure.
( 2 ) The method for producing a cyclized compound according to the above (1), wherein the carbon dioxide is carbon dioxide having a pressure of 7.3 MPa to 50 MPa and a temperature of 31 ° C to 300 ° C.
(3) ketone is, the general formula (1)
（式中、Ｒ１、Ｒ２及びＲ３は、それぞれ同一又は相異なる置換基であり、アルキル基、アルケニル基、アルキニル基、アリール基、カルボニル基、シアノ基、アミノ基を表す。また、Ｒ１及びＲ２が一緒になり環状構造の一部を形成しても良い。）で表される化合物であることを特徴とする上記（１）に記載の環化化合物の製造方法。
（４）ビニルケトンが、一般式（２）
(In the formula, R 1, R 2 and R 3 are the same or different substituents, and each represents an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a carbonyl group, a cyano group or an amino group. And a part of the cyclic structure may be formed together). The method for producing a cyclized compound according to (1) above, wherein
(4) Biniruketo down the general formula (2)
（式中、Ｒ４、Ｒ５、Ｒ６、Ｒ７は、それぞれ同一又は相異なる置換基であり、アルキル基、アルケニル基、アルキニル基、アリール基を表す。また、Ｒ４とＲ５、Ｒ４とＲ６、Ｒ４とＲ７、Ｒ５とＲ６、Ｒ５とＲ７、又はＲ６とＲ７が一緒になり環状構造の一部を形成しても良い。）で表される化合物であることを特徴とする上記（１）に記載の環化化合物の製造方法。
（５）ケトンが、シクロペンタノン、メチルシクロペンタノン、シクロペンタジオン、メチルシクロペンタジオン、シクロヘキサノン、メチルシクロヘキサノン、シクロヘキサジオン、メチルシクロヘキサジオン、シクロヘプタノン、メチルシクロヘプタノン、シクロヘプタジオン、メチルシクロヘプタジオン、アセトン、ブタノン、ペンタノン、ペンタジオン、ヘキサノン、ヘキサジオン、ヘプタノン、ヘプタジオン及びそれらの誘導体から選ばれることを特徴とする請求項１に記載の環化化合物の製造方法。
（６）ビニルケトンが、ブテノン、ペンテノン、へキセノン、ヘプテノン、オクテノン、フェニルブテノン、フェニルペンテノン及びその誘導体から選ばれることを特徴とする上記（１）に記載の環化化合物の製造方法。
（７）ケトンが、２−メチルシクロヘキサン−１，３−ジオン、シクロヘキサン−１，３−ジオン、シクロヘキサノン、２−メチルシクロヘキサノン、シクロペンタノン、２−メチルシクロペンタノン、シクロペンタ−１，３−ジオン、２−メチルシクロペンタ−１，３−ジオン、２−メチルシクロヘプタノン、２−メチルシクロヘプタ−１，３−ノン、シクロヘプタ−１，３−ジオン、ヘプタン−３−オン、ペンタ−２，４−ジオン、１，３−ジフェニルペンタン−２−オン、アセトン、ブタ−２−オン、ペンタ−２−オン、ペンタ−３−オン、ヘキサ−２−オン、ヘキサ−３−オン及びそれらの誘導体から選ばれることを特徴とする上記（１）に記載の環化化合物の製造方法。
（８）ビニルケトンが、３−ブテン−２−オン、３−ペンテン−２−オン、１−ペンテン−３−オン、メチル−３−ペンテン−２−オン、３−ヘキセン−２−オン、１−ヘキセン−３−オン、４−ヘキセン−３−オン、メチル−３−ヘキセン−２−オン、３−ヘプテン−２−オン、１−ヘプテン−３−オン、４−ヘプテン−３−オン、２−ヘプテン−４−オン、メチル−３−ヘプテン−２−オン、３−オクテン−２−オン、１−オクテン−３−オン、４−オクテン−３−オン、５−オクテン−４−オン、２−オクテン−３−オン、メチル−３−オクテン−２−オン、フェニルペンテン−３−オン及びその誘導体から選ばれることを特徴とする上記（１）に記載の環化化合物の製造方法。
（９）環化反応又は縮環反応が、ロビンソン反応であることを特徴とする上記（１）に記載の環化化合物の製造方法。
（１０）環化反応又は縮環反応が、バッチ方式であることを特徴とする上記（１）に記載の環化化合物の製造方法。
（１１）環化反応又は縮環反応が、連続方式であることを特徴とする上記（１）に記載の環化化合物の製造方法。
（１２）環化化合物が、ステロイド環化生成物であることを特徴とする上記（１）に記載の環化化合物の製造方法。
(In the formula, R4, R5, R6 and R7 are the same or different substituents, and each represents an alkyl group, an alkenyl group, an alkynyl group or an aryl group. R4 and R5, R4 and R6, R4 and R7) , R5 and R6, R5 and R7, or R6 and R7 may be combined to form part of a cyclic structure.), The ring according to (1) above Method for producing chemical compound.
(5) ketone is cyclopentanone, cyclopentanone, cyclopentadione, methylcyclopentadienyl dione, cyclohexanone, methyl cyclohexanone, cyclohexanol dione, methyl cyclohexadione, cycloheptanone, methyl cycloheptanone, cyclohepta 2. The method for producing a cyclized compound according to claim 1, which is selected from dione, methylcycloheptadione, acetone, butanone, pentanone, pentadione, hexanone, hexadione, heptanone, heptadione and derivatives thereof.
(6) Biniruketo emissions is, butenoic, pentenoic, to xenon, heptenone, Okutenon, phenyl Bed tenon, phenyl cyclopentenone and a manufacturing method of a cyclic compound according to the above (1), characterized in that it is selected from its derivatives.
(7) ketone is 2-methylcyclohexane-1,3-dione, cyclohexane-1,3-dione, cyclohexanone, 2-methylcyclohexanone, cyclopentanone, 2-methyl-cyclopentanone, cyclopenta-1,3 Dione, 2-methylcyclopenta-1,3-dione, 2-methylcycloheptanone, 2-methylcyclohepta-1,3-none, cyclohepta-1,3-dione, heptane-3-one, penta-2 , 4-dione, 1,3-diphenylpentan-2-one, acetone, but-2-one, penta-2-one, penta-3-one, hexa-2-one, hexa-3-one and their The method for producing a cyclized compound according to the above (1), which is selected from derivatives.
(8) Biniruketo emissions is, 3-buten-2-one, 3-penten-2-one, 1-pentene-3-one, methyl-3-penten-2-one, 3-hexene-2-one, 1 -Hexen-3-one, 4-hexen-3-one, methyl-3-hexen-2-one, 3-hepten-2-one, 1-hepten-3-one, 4-hepten-3-one, 2 -Hepten-4-one, methyl-3-hepten-2-one, 3-octen-2-one, 1-octen-3-one, 4-octen-3-one, 5-octen-4-one, 2 The method for producing a cyclized compound according to (1) above, which is selected from -octen-3-one, methyl-3-octen-2-one, phenylpenten-3-one and derivatives thereof.
( 9 ) The method for producing a cyclized compound according to the above (1), wherein the cyclization reaction or the condensation reaction is a Robinson reaction.
( 10 ) The method for producing a cyclized compound according to the above (1), wherein the cyclization reaction or the condensation reaction is a batch method.
( 11 ) The method for producing a cyclized compound as described in (1) above, wherein the cyclization reaction or the condensation reaction is a continuous method.
( 12 ) The method for producing a cyclized compound according to (1) above, wherein the cyclized compound is a steroid cyclization product.
次に、本発明について更に詳細に説明する。
本発明は、二酸化炭素、即ち、超臨界二酸化炭素、亜臨界二酸化炭素ないし加圧二酸化炭素の存在下に、ケトン類とビニルケトン類とを反応基質として、環化反応又は縮環反応を進行させることにより環化化合物を製造することを特徴とするものであり、超臨界二酸化炭素、亜臨界二酸化炭素ないし加圧二酸化炭素を反応媒体とすることで、有機溶媒を用いることなく、従来のプロセスに比べ、短い反応時間で環化化合物を製造することを可能とするものである。本発明は、二酸化炭素の存在下での反応プロセスによって、従来の技術では困難であった、環化化合物を選択的・効率的に製造する技術を提供するものである。本発明を実施するに当たっては、反応圧力及び反応温度を適宜組み合わせることにより、効率良く目的化合物を製造することができる。従来、加圧二酸化炭素を利用して、有機化合物の合成反応を研究した例は数多くあり、加圧二酸化炭素を利用して環化化合物が合成できることは、例えば、ディールス−アルダー反応、脱水反応による環状エーテル合成、ジオールとケトンとの反応によるアセタール合成が、良く知られた実証例である。しかし、ケトン類とビニルケトン類との反応であるロビンソン反応から環状化合物を製造した例はこれまでに無く、本発明によりはじめて実証されたものである。
Next, the present invention will be described in more detail.
The present invention allows a cyclization reaction or a condensation reaction to proceed using ketones and vinyl ketones as reaction substrates in the presence of carbon dioxide, that is, supercritical carbon dioxide, subcritical carbon dioxide or pressurized carbon dioxide. It is characterized by producing a cyclized compound by using supercritical carbon dioxide, subcritical carbon dioxide or pressurized carbon dioxide as a reaction medium, and without using an organic solvent, compared to conventional processes This makes it possible to produce a cyclized compound in a short reaction time. The present invention provides a technique for selectively and efficiently producing a cyclized compound, which has been difficult with conventional techniques, by a reaction process in the presence of carbon dioxide. In practicing the present invention, the target compound can be efficiently produced by appropriately combining the reaction pressure and the reaction temperature. Conventionally, there are many examples of researches on synthetic reactions of organic compounds using pressurized carbon dioxide, and the ability to synthesize cyclized compounds using pressurized carbon dioxide is due to, for example, Diels-Alder reaction and dehydration reaction. Cyclic ether synthesis and acetal synthesis by reaction of diol and ketone are well known demonstration examples. However, there has never been an example of producing a cyclic compound from the Robinson reaction, which is a reaction between ketones and vinyl ketones, and this was demonstrated for the first time by the present invention.
本発明の合成反応に用いる、二酸化炭素としては、超臨界二酸化炭素、亜臨界二酸化炭素ないし加圧二酸化炭素が挙げられ、通常、圧力０．１ＭＰａ〜１００ＭＰａ、温度０℃〜５００℃の二酸化炭素が用いられるが、好ましくは、圧力７．３ＭＰａ〜１００ＭＰａ、温度３１℃〜５００℃、更に好ましくは、７．３ＭＰａ〜５０ＭＰａ、温度３１℃〜３００℃の二酸化炭素が用いられる。また、反応に用いる二酸化炭素としては、必ずしも二酸化炭素のみを用いる必要は無く、二酸化炭素とは別な気体ないし液体ないし固体と混合した二酸化炭素でも良い。例えば、二酸化炭素と、水素、酸素、窒素、フッ素、塩素、臭素、アンモニア、アセチレン、メタン、エタン、プロパン、エチレン、プロピレン、ヘリウム、ネオン、アルゴン、クリプトン、キセノン等のガスとの混合ガスでも構わない。通常、１０％以上純度を持つ二酸化炭素が用いられるが、好ましくは５０％以上の純度を持つ二酸化炭素、更に好ましくは８０％以上の純度を持つ二酸化炭素が用いられる。本発明の反応は、反応基質として、ケトン類及びビニルケトン類の含まれる反応系に対して適応可能であり、目的とする環化化合物、反応基質の種類等に応じて、最適な反応温度、反応圧力を適宜選定し、反応を遂行する。 Examples of carbon dioxide used in the synthesis reaction of the present invention include supercritical carbon dioxide, subcritical carbon dioxide and pressurized carbon dioxide, and carbon dioxide having a pressure of 0.1 MPa to 100 MPa and a temperature of 0 ° C. to 500 ° C. is usually used. Preferably, carbon dioxide having a pressure of 7.3 MPa to 100 MPa and a temperature of 31 ° C. to 500 ° C., more preferably 7.3 MPa to 50 MPa, and a temperature of 31 ° C. to 300 ° C. is used. Moreover, as carbon dioxide used for the reaction, it is not always necessary to use only carbon dioxide, and carbon dioxide mixed with gas, liquid, or solid different from carbon dioxide may be used. For example, a mixed gas of carbon dioxide and hydrogen, oxygen, nitrogen, fluorine, chlorine, bromine, ammonia, acetylene, methane, ethane, propane, ethylene, propylene, helium, neon, argon, krypton, xenon, or the like may be used. Absent. Usually, carbon dioxide having a purity of 10% or more is used, preferably carbon dioxide having a purity of 50% or more, more preferably carbon dioxide having a purity of 80% or more. The reaction of the present invention can be applied to a reaction system containing ketones and vinyl ketones as a reaction substrate, and the optimum reaction temperature and reaction depending on the target cyclized compound, type of reaction substrate, etc. Select the pressure appropriately and carry out the reaction.
本発明の方法で用いる反応基質は、特に限定されるものではないが、ケトン類として、例えば、脂肪族ケトン、更に、これらのジケトン、トリケトン、テトラケトン、脂肪族環状ケトン、更に、これらのジケトン、トリケトン、テトラケトン、そして、それらのケトン類の誘導体、芳香族ケトン、これらのジケトン、トリケトン、テトラケトン等のケトン類、そして、それらのケトン類の誘導体、脂肪族アルデヒド、これらのジアルデヒド、トリアルデヒド、テトラアルデヒド、そして、それらのアルデヒド類の誘導体、脂肪族環状アルデヒド、これらのジアルデヒド、トリアルデヒド、テトラアルデヒド、そして、それらのアルデヒド類の誘導体が挙げられる。また、ビニルケトン類として、例えば、アルキルビニルケトン類、シクロアルキルビニルケトン類、アリールビニルケトン類、シクロアルキルビニルケトン類、アリールアルキルビニルケトン類、アリールシクロアルキルビニルケトン類及びそれらの誘導体が挙げられる。これらのケトン類とビニルケトン類との反応による、環状ケトン構造を有する環状化合物の合成プロセスが、本発明の代表的な反応例として挙げられる。 The reaction substrate used in the method of the present invention is not particularly limited. Examples of the ketones include aliphatic ketones, further diketones, triketones, tetraketones, aliphatic cyclic ketones, and further diketones. Triketones, tetraketones, and derivatives of these ketones, aromatic ketones, diketones, triketones, ketones such as tetraketones, and derivatives of these ketones, aliphatic aldehydes, these dialdehydes, trialdehydes, Examples include tetraaldehydes and derivatives of these aldehydes, aliphatic cyclic aldehydes, these dialdehydes, trialdehydes, tetraaldehydes, and derivatives of these aldehydes. Examples of vinyl ketones include alkyl vinyl ketones, cycloalkyl vinyl ketones, aryl vinyl ketones, cycloalkyl vinyl ketones, arylalkyl vinyl ketones, arylcycloalkyl vinyl ketones, and derivatives thereof. A typical reaction example of the present invention is a process for synthesizing a cyclic compound having a cyclic ketone structure by a reaction between these ketones and vinyl ketones.
本発明において採用される、反応基質の具体例としては、例えば、ケトン類としては、シクロペンタノン、２−メチルシクロペンタノン、３−メチルシクロペンタノン、２−エチルシクロペンタノン、３−エチルシクロペンタノン、２，５−ジメチルシクロペンタノン、２，５−ジエチルシクロペンタノン、シクロヘキサノン、２−メチルシクロヘキサノン、３−メチルシクロヘキサノン、４−メチルシクロヘキサノン、２−エチルシクロヘキサノン、３−エチルシクロヘキサノン、４−エチルシクロヘキサノン、２，６−ジメチルシクロヘキサノン、２，６−ジエチルシクロヘキサノン、シクロヘプタノン、２−メチルシクロヘプタノン、３−メチルシクロヘプタノン、４−メチルシクロヘプタノン、２−エチルシクロヘプタノン、３−エチルシクロヘプタノン、４−エチルシクロヘプタノン、２，７−ジメチルシクロヘプタノン、２，７−ジエチルシクロヘプタノン、シクロオクタノン、２−メチルシクロオクタノン、３−メチルシクロオクタノン、４−メチルシクロオクタノン、２−エチルシクロオクタノン、３−エチルシクロオクタノン、４−エチルシクロオクタノン、シクロペンタ−１，３−ジオン、２−メチルシクロペンタ−１，３−ジオン、４−メチルシクロペンタ−１，３−ジオン、シクロヘキサ−１，３−ジオン、２−メチルシクロヘキサ−１，３−ジオン、４−メチルシクロヘキサ−１，３−ジオン、シクロヘプタ−１，３−ジオン、２−メチルシクロヘプタ−１，３−ジオン、４−メチルシクロヘプタ−１，３−ジオン、シクロオクタ−１，３−ジオン、２−メチルシクロオクタ−１，３−ジオン、４−メチルシクロオクタ−１，３−ジオン、５−メチルシクロオクタ−１，３−ジオン、６−メチルシクロオクタ−１，３−ジオン、２−エチルシクロオクタ−１，３−ジオン、４−エチルシクロオクタ−１，３−ジオン、５−エチルシクロオクタ−１，３−ジオン、６−エチルシクロオクタ−１，３−ジオン、シクロヘキサ−１，３，５−トリオン、２−メチルシクロヘキサ−１，３，５−トリオン、２，４−ジメチルシクロヘキサ−１，３，５−トリオン、２，４，６−トリメチルシクロヘキサ−１，３，５−トリオン、シクロヘプタ−１，３，５，７−テトラオン、２−メチルシクロヘプタ−１，３，５，７−テトラオン、２，４−ジメチルシクロヘプタ−１，３，５，７−テトラオン、２，４，６−トリメチルシクロヘプタ−１，３，５，７−テトラオン、アセトン、２−ブタノン、２−ペンタノン、３−ペンタノン、２−ヘキサノン、３−ヘキサノン、２−ヘプタノン、３−ヘプタノン、４−ヘプタノン、２−オクタノン、３−オクタノン、４−オクタノン、２，４−ペンタジオン、２，４−ヘキサジオン、２，５−ヘキサジオン、２，４−ヘプタジオン、２，５−ヘプタジオン、２，６−ヘプタジオン、２，４−オクタジオン、２，５−オクタジオン、２，６−オクタジオン、２，７−オクタジオン等が挙げられる。 Specific examples of the reaction substrate employed in the present invention include, for example, ketones such as cyclopentanone, 2-methylcyclopentanone, 3-methylcyclopentanone, 2-ethylcyclopentanone, 3-ethyl. Cyclopentanone, 2,5-dimethylcyclopentanone, 2,5-diethylcyclopentanone, cyclohexanone, 2-methylcyclohexanone, 3-methylcyclohexanone, 4-methylcyclohexanone, 2-ethylcyclohexanone, 3-ethylcyclohexanone, 4 -Ethylcyclohexanone, 2,6-dimethylcyclohexanone, 2,6-diethylcyclohexanone, cycloheptanone, 2-methylcycloheptanone, 3-methylcycloheptanone, 4-methylcycloheptanone, 2-ethylcycloheptanone, 3-D Lucycloheptanone, 4-ethylcycloheptanone, 2,7-dimethylcycloheptanone, 2,7-diethylcycloheptanone, cyclooctanone, 2-methylcyclooctanone, 3-methylcyclooctanone, 4- Methylcyclooctanone, 2-ethylcyclooctanone, 3-ethylcyclooctanone, 4-ethylcyclooctanone, cyclopenta-1,3-dione, 2-methylcyclopenta-1,3-dione, 4-methylcyclo Penta-1,3-dione, cyclohexa-1,3-dione, 2-methylcyclohexa-1,3-dione, 4-methylcyclohexa-1,3-dione, cyclohepta-1,3-dione, 2- Methylcyclohepta-1,3-dione, 4-methylcyclohepta-1,3-dione, cycloocta-1,3-dione, 2 Methylcycloocta-1,3-dione, 4-methylcycloocta-1,3-dione, 5-methylcycloocta-1,3-dione, 6-methylcycloocta-1,3-dione, 2-ethylcyclo Octa-1,3-dione, 4-ethylcycloocta-1,3-dione, 5-ethylcycloocta-1,3-dione, 6-ethylcycloocta-1,3-dione, cyclohexa-1,3 5-trione, 2-methylcyclohexa-1,3,5-trione, 2,4-dimethylcyclohexa-1,3,5-trione, 2,4,6-trimethylcyclohexa-1,3,5- Trione, cyclohepta-1,3,5,7-tetraone, 2-methylcyclohepta-1,3,5,7-tetraone, 2,4-dimethylcyclohepta-1,3,5,7-tetraone, 2, 4 , 6-Trimethylcyclohepta-1,3,5,7-tetraone, acetone, 2-butanone, 2-pentanone, 3-pentanone, 2-hexanone, 3-hexanone, 2-heptanone, 3-heptanone, 4-heptanone 2-octanone, 3-octanone, 4-octanone, 2,4-pentadione, 2,4-hexadione, 2,5-hexadione, 2,4-heptadione, 2,5-heptadione, 2,6-heptadione, 2, , 4-octadione, 2,5-octadione, 2,6-octadione, 2,7-octadione, and the like.
また、ビニルケトン類の具体例としては、例えば、３−ブテン−２−オン、３−ペンテン−２−オン、１−ペンテン−３−オン、メチル−３−ペンテン−２−オン、３−ヘキセン−２−オン、１−ヘキセン−３−オン、４−ヘキセン−３−オン、メチル−３−ヘキセン−２−オン、３−ヘプテン−２−オン、１−ヘプテン−３−オン、４−ヘプテン−３−オン、２−ヘプテン−４−オン、メチル−３−ヘプテン−２−オン、３−オクテン−２−オン、１−オクテン−３−オン、４−オクテン−３−オン、５−オクテン−４−オン、２−オクテン−３−オン、メチル−３−オクテン−２−オン、フェニルペンテン−３−オン等が挙げられる。 Specific examples of vinyl ketones include, for example, 3-buten-2-one, 3-penten-2-one, 1-penten-3-one, methyl-3-penten-2-one, and 3-hexene- 2-one, 1-hexen-3-one, 4-hexene-3-one, methyl-3-hexen-2-one, 3-hepten-2-one, 1-hepten-3-one, 4-heptene- 3-one, 2-hepten-4-one, methyl-3-hepten-2-one, 3-octen-2-one, 1-octen-3-one, 4-octen-3-one, 5-octene- 4-one, 2-octen-3-one, methyl-3-octen-2-one, phenylpenten-3-one and the like can be mentioned.
反応基質のケトン類とビニルケトン類とは、モル比で、１：０．１〜１：１０の範囲、好ましくは１：０．５〜１：５の範囲で使用される。このとき、二酸化炭素は、反応基質１モルに対して、０．１〜１００００の範囲で使用するのが好ましい。本発明の製造方法では、環化化合物としては、反応基質、反応温度、圧力等の条件に応じて、種々の環化化合物が製造できるが、例えば、２−メチルシクロヘキサン−１，３−ジオンと、３−ブテン−２−オンとの反応からは、８ａ−メチル−３，４，８，８ａ−テトラヒドロ−２Ｈ，７Ｈ−ナフタレン−１，６−ジオンが製造できる。また、例えば、反応式１から３、表５，６に記載された、環化化合物も同様にして製造することが可能であり、本発明では、同様にして種々の環化化合物を合成することができる。 The reaction substrate ketones and vinyl ketones are used in a molar ratio of 1: 0.1 to 1:10, preferably 1: 0.5 to 1: 5. At this time, it is preferable to use carbon dioxide in the range of 0.1 to 10,000 with respect to 1 mol of the reaction substrate. In the production method of the present invention, as the cyclized compound, various cyclized compounds can be produced according to the conditions such as the reaction substrate, reaction temperature, and pressure. For example, 2-methylcyclohexane-1,3-dione and From the reaction with 3-buten-2-one, 8a-methyl-3,4,8,8a-tetrahydro-2H, 7H-naphthalene-1,6-dione can be produced. Further, for example, the cyclized compounds described in Reaction Formulas 1 to 3 and Tables 5 and 6 can be produced in the same manner. In the present invention, various cyclized compounds are synthesized in the same manner. Can do.
本発明においては、上記基質及び二酸化炭素を反応器に導入して、所定の反応時間で合成を実施する。このとき、例えば、従来公知の、高温高圧反応で用いられる反応プロセス又は装置が適用でき、例えば、バッチ式の高温高圧反応装置、又は連続式の流通式高温高圧反応装置を使用することができるが、本発明は、これらのプロセス又は装置については、特に限定されるものではない。本発明の方法では、従来、多段の反応プロセスで行われていた環化化合物の製造工程を、一段階の工程で実施することができるので、製造コストは大幅に低減できる。また、従来用いられていた、強酸、強塩基、有機溶媒を使用する必要がないので、反応後に、中和処理、無害化処理、廃水、廃物処理等を行う必要がない。 In the present invention, the substrate and carbon dioxide are introduced into a reactor, and synthesis is carried out for a predetermined reaction time. At this time, for example, a conventionally known reaction process or apparatus used in a high-temperature high-pressure reaction can be applied. For example, a batch-type high-temperature high-pressure reaction apparatus or a continuous flow-type high-temperature high-pressure reaction apparatus can be used. The present invention is not particularly limited with respect to these processes or apparatuses. In the method of the present invention, the production process of the cyclized compound, which has been conventionally carried out in a multistage reaction process, can be carried out in a single stage process, so that the production cost can be greatly reduced. In addition, since it is not necessary to use a strong acid, a strong base, or an organic solvent, which has been conventionally used, it is not necessary to perform neutralization treatment, detoxification treatment, waste water, waste treatment, or the like after the reaction.
このように、本発明は、従来の合成工程のように、合成反応・分離操作の繰返しを行うことを必要としない、一段階反応であることから、目的の有機化合物を合成するに要する操作は簡単であり、合成反応時間は、極めて短時間となる。本発明による反応時間は、反応基質、目的とする化合物、反応条件等により相違するが、通常、５分〜２４時間程度の反応時間で環化化合物の製造が可能であり、短時間内に、環化化合物を大量生産することを可能とする。本発明では、後述する実施例に示すように、例えば、基質及び二酸化炭素をバッチ式反応装置に導入し、温度、圧力、反応時間を変化させることにより、所定の反応生成物を選択的に製造できる。こうした合成反応により、通常は、幾つもの反応を経て合成される環状化合物が、一段階で合成できる。しかも、例えば、その反応基質の転化率としては９９％を達成でき、また、目的とする化合物の選択率としては７５％が得られる。そして、本発明の反応では、副反応成生物が少ないが、このことは、驚異的なことであり、本発明が、化合物の選択性が非常に高く、効率の良い環化化合物の製造方法であることを示すものである。 Thus, since the present invention is a one-step reaction that does not require repeated synthesis reaction / separation operation unlike the conventional synthesis process, the operation required to synthesize the target organic compound is as follows. It is simple and the synthesis reaction time is extremely short. The reaction time according to the present invention varies depending on the reaction substrate, target compound, reaction conditions, etc., but usually a cyclized compound can be produced in a reaction time of about 5 minutes to 24 hours, and within a short time, It enables mass production of cyclized compounds. In the present invention, as shown in Examples described later, for example, a predetermined reaction product is selectively produced by introducing a substrate and carbon dioxide into a batch reactor and changing temperature, pressure, and reaction time. it can. By such a synthetic reaction, a cyclic compound usually synthesized through several reactions can be synthesized in one step. In addition, for example, the conversion rate of the reaction substrate can be 99%, and the target compound selectivity is 75%. In the reaction of the present invention, there are few side reaction products. This is surprising, and the present invention is an efficient method for producing a cyclized compound with very high compound selectivity. It shows that there is.
本発明は、二酸化炭素の存在下に、ケトン類とビニルケトン類とを反応基質として、両者を反応させる、新規な、環化化合物の製造方法に係るものであり、本発明により、（１）反応容器内の化合物を、従来、反応・分離操作を繰り返すことで合成していた工程を、一段階で効率的に行うことを可能とする環化化合物の製造方法を提供できる、（２）反応に選択性があり、目的とする環化化合物を、高い選択性で、高収率で合成することができる、（３）一段階反応であり、反応時間が５分〜２４時間という、短時間で、複雑な化学反応を遂行することができる、（４）反応時間が短いため、短時間に大量の化合物を合成するのに適している、（５）反応工程において、分離・精製工程等を繰り返す必要がないため、操作が簡便である、（６）有機溶媒、酸、アルカリ等を極力使用せずに反応を遂行できるため、生成物に不純物の混入する恐れが少ない、（７）二酸化炭素は常温で気体であるため、生成物との分離が容易である、（８）廃水、廃物がほとんど発生しない合成方法であって、廃水、廃物の処理を必要としない、環境にやさしい環化化合物の合成方法を提供できる、という格別の効果が奏される。 The present invention relates to a novel method for producing a cyclized compound in which ketones and vinyl ketones are used as reaction substrates in the presence of carbon dioxide, and both are reacted. According to the present invention, (1) reaction It is possible to provide a method for producing a cyclized compound that can efficiently perform the process of synthesizing a compound in a container by repeating the reaction / separation operation in one step, (2) There is selectivity, and the desired cyclized compound can be synthesized with high selectivity and high yield. (3) It is a one-step reaction, and the reaction time is 5 minutes to 24 hours. (4) It is suitable for synthesizing a large amount of compounds in a short time because the reaction time is short. (5) In the reaction process, separation and purification processes are repeated. Since it is not necessary, the operation is simple. (6 The reaction can be carried out with minimal use of organic solvents, acids, alkalis, etc., so there is little risk of impurities being mixed into the product. (7) Since carbon dioxide is a gas at room temperature, it can be easily separated from the product. (8) It is a synthesis method in which waste water and waste are hardly generated, and it is possible to provide an environment-friendly synthesis method of a cyclized compound that does not require treatment of waste water and waste. .
次に、本発明の環化化合物の製造方法を、実施例に基づいて具体的に説明するが、本発明は、これらの実施例によって何ら限定されるものではない。 Next, although the manufacturing method of the cyclization compound of this invention is demonstrated concretely based on an Example, this invention is not limited at all by these Examples.
本実施例では、バッチ式で２−メチルシクロヘキサン−１，３−ジオンからステロイド環化生成物である８ａ−メチル−３，４，８，８ａ−テトラヒドロ−２Ｈ，７Ｈ−ナフタレン−１，６−ジオン（化合物４）を圧力・温度一定の条件下に製造した。２５ｍＬの耐圧容器に２−メチルシクロヘキサン−１，３−ジオン０．２ｇ（１．６ｍｍｏｌ）、３−ブテン−２−オン０．２ｍＬ（２．３ｍｍｏｌ、１．４当量）、酸化マグネシウム５０ｍｇを入れた。耐圧容器中に、室温（２５℃）において、二酸化炭素を導入して、圧力を１ＭＰａにした。その後、それを１００℃の油浴に入れた後、更に、二酸化炭素を導入して表１に記載の圧力に調整して２時間反応させた。反応終了後、氷水で急冷し、十分容器が冷却された後に、耐圧容器を開封した。得られた生成物は、フィルターで触媒を除去して、そのままエーテルで薄めて、ＧＣ−ＭＳ／ＭＳを用いて分析した。２−メチルシクロヘキサン−１，３−ジオンの転化率、及び、目的物である８ａ−メチル−３，４，８，８ａ−テトラヒドロ−２Ｈ，７Ｈ−ナフタレン−１，６−ジオン（化合物４）の収率を、表１に示す。以上の結果から、脱水した化合物４の収量は少ないものの、化合物３の環化化合物を得ることができた。しかし、反応温度が１００℃の条件下では、環化前の化合物２が主に生成することが分かった。 In this example, the steroid cyclization product 8a-methyl-3,4,8,8a-tetrahydro-2H, 7H-naphthalene-1,6-, which is a steroid cyclization product from 2-methylcyclohexane-1,3-dione in batch mode. Dione (compound 4) was produced under conditions of constant pressure and temperature. Put 2-methylcyclohexane-1,3-dione 0.2 g (1.6 mmol), 3-buten-2-one 0.2 mL (2.3 mmol, 1.4 eq) and magnesium oxide 50 mg in a 25 mL pressure vessel. It was. Carbon dioxide was introduced into the pressure vessel at room temperature (25 ° C.) to make the pressure 1 MPa. Then, after putting it in a 100 degreeC oil bath, carbon dioxide was introduce | transduced and it adjusted to the pressure of Table 1, and was made to react for 2 hours. After completion of the reaction, the reaction vessel was quenched with ice water, and after the vessel was sufficiently cooled, the pressure vessel was opened. The obtained product was analyzed by GC-MS / MS after removing the catalyst with a filter, diluting with ether as it was. Conversion of 2-methylcyclohexane-1,3-dione and the target 8a-methyl-3,4,8,8a-tetrahydro-2H, 7H-naphthalene-1,6-dione (compound 4) The yield is shown in Table 1. From the above results, a cyclized compound of Compound 3 could be obtained although the yield of dehydrated Compound 4 was small. However, it was found that the compound 2 before cyclization was mainly produced under the reaction temperature of 100 ° C.
実施例１と同様の実験において、反応温度を１８０℃にして検討した。原料の２−メチルシクロヘキサン−１，３−ジオンの転化率、目的物である８ａ−メチル−３，４，８，８ａ−テトラヒドロ−２Ｈ，７Ｈ−ナフタレン−１，６−ジオン（化合物４）の収率を、表２に示す。反応温度が１００℃の時に比べて、最終的な環化化合物４を収率良く得ることができた。 In the same experiment as in Example 1, the reaction temperature was set at 180 ° C. Conversion of raw material 2-methylcyclohexane-1,3-dione, target 8a-methyl-3,4,8,8a-tetrahydro-2H, 7H-naphthalene-1,6-dione (compound 4) The yield is shown in Table 2. Compared to when the reaction temperature is 100 ° C., the final cyclized compound 4 could be obtained in good yield.
本実施例では、反応時間について、実施例２と同様に、温度を１８０℃、圧力を２０ＭＰａにして製造の検討を行った。原料の２−メチルシクロヘキサン−１，３−ジオンの転化率、目的物である、８ａ−メチル−３，４，８，８ａ−テトラヒドロ−２Ｈ，７Ｈ−ナフタレン−１，６−ジオンの収率をそれぞれ表３に示す。 In this example, the reaction time was examined in the same manner as in Example 2 at a temperature of 180 ° C. and a pressure of 20 MPa. The conversion rate of 2-methylcyclohexane-1,3-dione as a raw material and the yield of 8a-methyl-3,4,8,8a-tetrahydro-2H, 7H-naphthalene-1,6-dione, which is the target product, Each is shown in Table 3.
本実施例では、実施例１と同様に、バッチ式でシクロペンタン−１，３−ジオンを用いて実験を行なった。２５ｍＬの耐圧容器にシクロペンタン−１，３−ジオン０．２ｇ（２．０ｍｍｏｌ）、３−ブテン−２−オン０．２ｍＬ（２．３ｍｍｏｌ，１．２当量）、酸化マグネシウム５０ｍｇを入れた。耐圧容器中に、室温（２５℃）において、二酸化炭素を導入し圧力を１ＭＰａにした。次いで、１００℃の油浴に入れた後、更に二酸化炭素を導入し表４に記載の圧力に調整して、２時間反応させた。反応後、氷水で急冷して十分容器が冷却された後に、耐圧容器を開封した。得られた生成物は、フィルターで触媒を除去し、そのままエーテルで薄めて、ＧＣ−ＭＳ／ＭＳを用いて分析した。その結果を表４に示す。これより、ロビンソン反応が進行し、化合物６〜１０の環化化合物が得られた。特に、シクロペンタンジオンを、反応基質とする場合には、転化率は、反応圧力が低い方が良い傾向を示すが、化合物１の収率が最も低いのは、１０ＭＰａ付近の臨界圧力近傍であることが分かった。 In this example, as in Example 1, an experiment was conducted using cyclopentane-1,3-dione in a batch manner. A 25 mL pressure vessel was charged with 0.2 g (2.0 mmol) of cyclopentane-1,3-dione, 0.2 mL (2.3 mmol, 1.2 equivalents) of 3-buten-2-one and 50 mg of magnesium oxide. Carbon dioxide was introduced into the pressure vessel at room temperature (25 ° C.) to make the pressure 1 MPa. Subsequently, after putting in a 100 degreeC oil bath, the carbon dioxide was introduce | transduced further, it adjusted to the pressure of Table 4, and was made to react for 2 hours. After the reaction, the pressure-resistant container was opened after the container was cooled sufficiently with ice water and sufficiently cooled. The resulting product was analyzed by GC-MS / MS after removing the catalyst with a filter, diluting with ether as it was. The results are shown in Table 4. From this, the Robinson reaction proceeded, and cyclized compounds of compounds 6 to 10 were obtained. In particular, when cyclopentanedione is used as the reaction substrate, the conversion rate tends to be better when the reaction pressure is lower, but the yield of Compound 1 is the lowest near the critical pressure around 10 MPa. I understood that.
本実施例では、より低温の３５℃で、実施例４と同様に実験した。得られた結果を表５に示す。これより、ロビンソン反応が進行し、化合物１０、１１の環状化合物が得られることが分かった。特に、化合物１１を製造するには、有機溶媒を用いた場合では、通常、５段階以上の反応操作が必要であるが、７ＭＰａのほぼ臨界圧力にある二酸化炭素（臨界点近傍）を用いると、１２．８％もの選択率で得ることができた。また、超臨界二酸化炭素（７ＭＰａ）以上では、より高圧にすることで、化合物１の生成を、押さえることができ、特に、９ＭＰａの圧力で最も生成を押さえることが可能となることが分かった。 In this example, the experiment was performed at a lower temperature of 35 ° C. as in Example 4. The results obtained are shown in Table 5. From this, it was found that the Robinson reaction progressed and the cyclic compounds of compounds 10 and 11 were obtained. In particular, in order to produce the compound 11, when an organic solvent is used, it is usually necessary to carry out a reaction operation of 5 steps or more. However, when carbon dioxide (near the critical point) at an approximately critical pressure of 7 MPa is used, A selectivity of 12.8% could be obtained. Further, it has been found that, at supercritical carbon dioxide (7 MPa) or higher, the generation of Compound 1 can be suppressed by increasing the pressure, and in particular, the generation can be suppressed most at a pressure of 9 MPa.
シクロへキサノンとその他のビニルケトン化合物との反応についても、実施例２と同様の条件（温度１８０℃、圧力２０ＭＰａ）で実験した。その結果を下記の表６に示す。 The reaction between cyclohexanone and other vinyl ketone compounds was also conducted under the same conditions as in Example 2 (temperature 180 ° C., pressure 20 MPa). The results are shown in Table 6 below.
各種ケトン類とブテノンとの反応についても、実施例２と同様の条件（温度１８０℃、圧力２０ＭＰａ）で実験した。その結果を、下記の表７に示す。 The reaction between various ketones and butenone was also conducted under the same conditions as in Example 2 (temperature 180 ° C., pressure 20 MPa). The results are shown in Table 7 below.
以上詳述したように、本発明は、二酸化炭素の存在下に、ケトン類とビニルケトン類とを反応基質として反応を遂行し、環化化合物を合成する新規な環化化合物の製造方法に係るものであり、本発明により、二酸化炭素、即ち、超臨界二酸化炭素、亜臨界二酸化炭素ないし加圧二酸化炭素の存在下の反応により、従来の、有機溶媒を使用する反応によっては、合成することが困難であった環化化合物を、短時間で、高選択性で製造する技術を提供することができる。本発明は、二酸化炭素の存在下に、上記反応基質を反応させることにより、化合物の選択的合成が可能であり、従来のように、合成反応・分離操作を繰返すことなく、一段階で、選択性及び収率の高い合成を可能とするものである。また、本発明は、短時間で、大量に環状化合物を製造することができ、しかも、有機溶媒、酸、アルカリ等を使用しないので、廃液、廃物の排出も少なく、それらの処理の必要性はないので、環境にやさしく、環化化合物を製造することができる。本発明は、このような利点を有する、新しい環化化合物の合成方法を提供するものとして有用である。
As described above in detail, the present invention relates to a novel method for producing a cyclized compound in which a reaction is carried out using ketones and vinyl ketones as reaction substrates in the presence of carbon dioxide to synthesize a cyclized compound. According to the present invention, it is difficult to synthesize by a reaction using an organic solvent by a reaction in the presence of carbon dioxide, that is, supercritical carbon dioxide, subcritical carbon dioxide or pressurized carbon dioxide. Thus, it is possible to provide a technique for producing the cyclized compound having a high selectivity in a short time. In the present invention, a compound can be selectively synthesized by reacting the above reaction substrate in the presence of carbon dioxide, and can be selected in one step without repeating the synthesis reaction / separation operation as in the prior art. It enables synthesis with high performance and yield. In addition, the present invention can produce a large amount of cyclic compounds in a short time, and since organic solvents, acids, alkalis, etc. are not used, there is little discharge of waste liquids and wastes, and there is no need for their treatment. Therefore, the cyclized compound can be produced environmentally friendly. The present invention is useful as a method for synthesizing a new cyclized compound having such advantages.
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