JP5039965B2 - Method for producing organic compound by microreactor catalytic reaction - Google Patents
Method for producing organic compound by microreactor catalytic reaction Download PDFInfo
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- JP5039965B2 JP5039965B2 JP2004043732A JP2004043732A JP5039965B2 JP 5039965 B2 JP5039965 B2 JP 5039965B2 JP 2004043732 A JP2004043732 A JP 2004043732A JP 2004043732 A JP2004043732 A JP 2004043732A JP 5039965 B2 JP5039965 B2 JP 5039965B2
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- allyl
- reaction
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- 150000002894 organic compounds Chemical class 0.000 title claims description 12
- 238000004519 manufacturing process Methods 0.000 title claims description 10
- 238000006555 catalytic reaction Methods 0.000 title claims description 6
- -1 carbamoyloxy group Chemical group 0.000 claims description 43
- 125000003118 aryl group Chemical group 0.000 claims description 28
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 239000003054 catalyst Substances 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 125000004104 aryloxy group Chemical group 0.000 claims description 21
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 20
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 19
- 239000003446 ligand Substances 0.000 claims description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 239000002994 raw material Substances 0.000 claims description 13
- 229910052723 transition metal Inorganic materials 0.000 claims description 12
- 150000003624 transition metals Chemical class 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 229910052763 palladium Inorganic materials 0.000 claims description 8
- 239000012736 aqueous medium Substances 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 239000012074 organic phase Substances 0.000 claims description 7
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 6
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical group C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 claims description 3
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000000532 dioxanyl group Chemical group 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 3
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical group C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 claims description 3
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 3
- 229910052697 platinum Inorganic materials 0.000 claims description 3
- 229910052703 rhodium Inorganic materials 0.000 claims description 3
- 239000010948 rhodium Substances 0.000 claims description 3
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 claims description 3
- 125000005208 trialkylammonium group Chemical group 0.000 claims description 3
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 229910052741 iridium Inorganic materials 0.000 claims description 2
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052759 nickel Inorganic materials 0.000 claims description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims 1
- 230000002209 hydrophobic effect Effects 0.000 claims 1
- 238000007363 ring formation reaction Methods 0.000 claims 1
- 239000000243 solution Substances 0.000 description 95
- 238000006243 chemical reaction Methods 0.000 description 74
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 45
- 239000007788 liquid Substances 0.000 description 34
- 238000007796 conventional method Methods 0.000 description 24
- 235000019270 ammonium chloride Nutrition 0.000 description 22
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
- 229920006395 saturated elastomer Polymers 0.000 description 22
- BKXPKNYXXNYCBX-UHFFFAOYSA-N ethyl 3-oxohept-6-enoate Chemical compound CCOC(=O)CC(=O)CCC=C BKXPKNYXXNYCBX-UHFFFAOYSA-N 0.000 description 20
- 239000007864 aqueous solution Substances 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 11
- 229910000027 potassium carbonate Inorganic materials 0.000 description 11
- CCCUVHHPYBWVOW-UHFFFAOYSA-K [Na+].[Na+].[Na+].[O-]S(=O)(=O)c1ccccc1.[O-]S(=O)(=O)c1ccccc1.[O-]S(=O)(=O)c1ccccc1 Chemical compound [Na+].[Na+].[Na+].[O-]S(=O)(=O)c1ccccc1.[O-]S(=O)(=O)c1ccccc1.[O-]S(=O)(=O)c1ccccc1 CCCUVHHPYBWVOW-UHFFFAOYSA-K 0.000 description 10
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 10
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 10
- TWKVUTXHANJYGH-UHFFFAOYSA-L allyl palladium chloride Chemical class Cl[Pd]CC=C.Cl[Pd]CC=C TWKVUTXHANJYGH-UHFFFAOYSA-L 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 238000009775 high-speed stirring Methods 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
- FWZUNOYOVVKUNF-UHFFFAOYSA-N allyl acetate Chemical compound CC(=O)OCC=C FWZUNOYOVVKUNF-UHFFFAOYSA-N 0.000 description 5
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 125000005587 carbonate group Chemical group 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 125000001624 naphthyl group Chemical group 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 125000004430 oxygen atom Chemical group O* 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 229910052710 silicon Inorganic materials 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000006579 Tsuji-Trost allylation reaction Methods 0.000 description 3
- 125000005595 acetylacetonate group Chemical group 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
- 239000012038 nucleophile Substances 0.000 description 3
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 3
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 2
- REIYHFWZISXFKU-UHFFFAOYSA-N Butyl acetoacetate Chemical compound CCCCOC(=O)CC(C)=O REIYHFWZISXFKU-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
- 125000005577 anthracene group Chemical group 0.000 description 2
- QUKGYYKBILRGFE-UHFFFAOYSA-N benzyl acetate Chemical compound CC(=O)OCC1=CC=CC=C1 QUKGYYKBILRGFE-UHFFFAOYSA-N 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
- 239000004305 biphenyl Chemical group 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([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
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000000068 chlorophenyl group Chemical group 0.000 description 2
- WJSDHUCWMSHDCR-VMPITWQZSA-N cinnamyl acetate Natural products CC(=O)OC\C=C\C1=CC=CC=C1 WJSDHUCWMSHDCR-VMPITWQZSA-N 0.000 description 2
- 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- GDWAYKGILJJNBB-UHFFFAOYSA-N diethyl 2-prop-2-enylpropanedioate Chemical compound CCOC(=O)C(CC=C)C(=O)OCC GDWAYKGILJJNBB-UHFFFAOYSA-N 0.000 description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 2
- DZCPEGJVQAREJZ-UHFFFAOYSA-N ethyl 3-oxo-7-phenylhept-6-enoate Chemical compound C(C)OC(CC(=O)CCC=CC1=CC=CC=C1)=O DZCPEGJVQAREJZ-UHFFFAOYSA-N 0.000 description 2
- ZZPMFCJULFHWPW-UHFFFAOYSA-N ethyl 3-oxodec-5-enoate Chemical compound C(C)OC(CC(=O)CC=CCCCC)=O ZZPMFCJULFHWPW-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000001207 fluorophenyl group Chemical group 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 125000006038 hexenyl group Chemical group 0.000 description 2
- 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 2
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 2
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 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 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
- HVAMZGADVCBITI-UHFFFAOYSA-M pent-4-enoate Chemical compound [O-]C(=O)CCC=C HVAMZGADVCBITI-UHFFFAOYSA-M 0.000 description 2
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- IDZAUPYMMSSVHP-UHFFFAOYSA-N pentyl 3-oxobutanoate Chemical compound CCCCCOC(=O)CC(C)=O IDZAUPYMMSSVHP-UHFFFAOYSA-N 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical group C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- DHGFMVMDBNLMKT-UHFFFAOYSA-N propyl 3-oxobutanoate Chemical compound CCCOC(=O)CC(C)=O DHGFMVMDBNLMKT-UHFFFAOYSA-N 0.000 description 2
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 150000003283 rhodium Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229930192474 thiophene Chemical group 0.000 description 2
- 125000003944 tolyl group Chemical group 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- HZYABSBSRWFZEG-BSWSSELBSA-N (1E,3E)-octa-1,3-dien-1-ol Chemical compound CCCC\C=C\C=C\O HZYABSBSRWFZEG-BSWSSELBSA-N 0.000 description 1
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 1
- JRTIUDXYIUKIIE-KZUMESAESA-N (1z,5z)-cycloocta-1,5-diene;nickel Chemical compound [Ni].C\1C\C=C/CC\C=C/1.C\1C\C=C/CC\C=C/1 JRTIUDXYIUKIIE-KZUMESAESA-N 0.000 description 1
- SDOFMBGMRVAJNF-KVTDHHQDSA-N (2r,3r,4r,5r)-6-aminohexane-1,2,3,4,5-pentol Chemical compound NC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO SDOFMBGMRVAJNF-KVTDHHQDSA-N 0.000 description 1
- MBVAQOHBPXKYMF-LNTINUHCSA-N (z)-4-hydroxypent-3-en-2-one;rhodium Chemical compound [Rh].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O MBVAQOHBPXKYMF-LNTINUHCSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 description 1
- 239000004912 1,5-cyclooctadiene Substances 0.000 description 1
- SWJXYIHLHXRZNT-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one;platinum Chemical compound [Pt].C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1.C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 SWJXYIHLHXRZNT-UHFFFAOYSA-N 0.000 description 1
- HEGHKROJUOXJFB-UHFFFAOYSA-K 2-[bis[2-(trimethylazaniumyl)ethyl]phosphanyl]ethyl-trimethylazanium trichloride Chemical compound [Cl-].[Cl-].[Cl-].C[N+](C)(C)CCP(CC[N+](C)(C)C)CC[N+](C)(C)C HEGHKROJUOXJFB-UHFFFAOYSA-K 0.000 description 1
- YTVQIZRDLKWECQ-UHFFFAOYSA-N 2-benzoylcyclohexan-1-one Chemical compound C=1C=CC=CC=1C(=O)C1CCCCC1=O YTVQIZRDLKWECQ-UHFFFAOYSA-N 0.000 description 1
- YVPXQMYCTGCWBE-UHFFFAOYSA-N 2-isocyano-2,4,4-trimethylpentane Chemical compound CC(C)(C)CC(C)(C)[N+]#[C-] YVPXQMYCTGCWBE-UHFFFAOYSA-N 0.000 description 1
- OMQHDIHZSDEIFH-UHFFFAOYSA-N 3-Acetyldihydro-2(3H)-furanone Chemical compound CC(=O)C1CCOC1=O OMQHDIHZSDEIFH-UHFFFAOYSA-N 0.000 description 1
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- OSDWBNJEKMUWAV-UHFFFAOYSA-N Allyl chloride Chemical compound ClCC=C OSDWBNJEKMUWAV-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000191368 Chlorobi Species 0.000 description 1
- UUMLNBDQAQIQKA-UHFFFAOYSA-L Cl[Pt](C1=C=CCC1)Cl Chemical compound Cl[Pt](C1=C=CCC1)Cl UUMLNBDQAQIQKA-UHFFFAOYSA-L 0.000 description 1
- FZQNSSAPUQJPSM-UHFFFAOYSA-M Cl[Rh].C12C=CC(C=C1)C2.C21C=CC(C=C2)C1 Chemical class Cl[Rh].C12C=CC(C=C1)C2.C21C=CC(C=C2)C1 FZQNSSAPUQJPSM-UHFFFAOYSA-M 0.000 description 1
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- 229910019142 PO4 Inorganic materials 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- 229910021604 Rhodium(III) chloride Inorganic materials 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
- WNHXJHGRIHUOTG-ONEGZZNKSA-N [(e)-but-2-enyl] acetate Chemical compound C\C=C\COC(C)=O WNHXJHGRIHUOTG-ONEGZZNKSA-N 0.000 description 1
- HHDBHSJOAURMII-UHFFFAOYSA-N [Ir].[Ir].C1CC=CCCC=C1 Chemical compound [Ir].[Ir].C1CC=CCCC=C1 HHDBHSJOAURMII-UHFFFAOYSA-N 0.000 description 1
- JFAIRQTYMSMUIR-UHFFFAOYSA-H [Na+].P(=O)([O-])([O-])C1=C(C=CC=C1)P(C1=C(C=CC=C1)P(=O)([O-])[O-])C1=C(C=CC=C1)P(=O)([O-])[O-].[Na+].[Na+].[Na+].[Na+].[Na+] Chemical compound [Na+].P(=O)([O-])([O-])C1=C(C=CC=C1)P(C1=C(C=CC=C1)P(=O)([O-])[O-])C1=C(C=CC=C1)P(=O)([O-])[O-].[Na+].[Na+].[Na+].[Na+].[Na+] JFAIRQTYMSMUIR-UHFFFAOYSA-H 0.000 description 1
- QCHMTQBWDPWNEZ-UHFFFAOYSA-N [Na].[Na].[Na].[Na].C(C=1OCC(N1)(C1=CC=CC=C1)C1=CC=CC=C1)C=1OCC(N1)(C1=CC=CC=C1)C1=CC=CC=C1 Chemical compound [Na].[Na].[Na].[Na].C(C=1OCC(N1)(C1=CC=CC=C1)C1=CC=CC=C1)C=1OCC(N1)(C1=CC=CC=C1)C1=CC=CC=C1 QCHMTQBWDPWNEZ-UHFFFAOYSA-N 0.000 description 1
- JFTILNNNVSEZOA-UHFFFAOYSA-N [Rh].C1=CCCCCCC1 Chemical class [Rh].C1=CCCCCCC1 JFTILNNNVSEZOA-UHFFFAOYSA-N 0.000 description 1
- NNQGTGHJXNVUBG-UHFFFAOYSA-N [Rh].C1C2C=CC1C=C2 Chemical compound [Rh].C1C2C=CC1C=C2 NNQGTGHJXNVUBG-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- TUOJAZRQYMQJER-UHFFFAOYSA-N benzonitrile;platinum Chemical compound [Pt].N#CC1=CC=CC=C1 TUOJAZRQYMQJER-UHFFFAOYSA-N 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
- 229940007550 benzyl acetate Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GPMUMMNTAZMBEC-UHFFFAOYSA-N bis(oxomethylidene)rhodium Chemical compound [Rh].[O+]#[C-].[O+]#[C-] GPMUMMNTAZMBEC-UHFFFAOYSA-N 0.000 description 1
- JKJWYKGYGWOAHT-UHFFFAOYSA-N bis(prop-2-enyl) carbonate Chemical compound C=CCOC(=O)OCC=C JKJWYKGYGWOAHT-UHFFFAOYSA-N 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- IRZVKYGINSGOOD-UHFFFAOYSA-N carbanide;palladium(2+) Chemical compound [CH3-].[CH3-].[Pd+2] IRZVKYGINSGOOD-UHFFFAOYSA-N 0.000 description 1
- SLFKPACCQUVAPG-UHFFFAOYSA-N carbon monoxide;nickel;triphenylphosphane Chemical compound O=C=[Ni]=C=O.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 SLFKPACCQUVAPG-UHFFFAOYSA-N 0.000 description 1
- SZQABOJVTZVBHE-UHFFFAOYSA-N carbon monoxide;rhodium Chemical compound [Rh].[Rh].[Rh].[Rh].[Rh].[Rh].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-] SZQABOJVTZVBHE-UHFFFAOYSA-N 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- WDTAKLSLSSTQOJ-UHFFFAOYSA-N chembl2063509 Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 WDTAKLSLSSTQOJ-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- HJSLFCCWAKVHIW-UHFFFAOYSA-N cyclohexane-1,3-dione Chemical compound O=C1CCCC(=O)C1 HJSLFCCWAKVHIW-UHFFFAOYSA-N 0.000 description 1
- JJQVHODEIZDXSW-UHFFFAOYSA-N cycloocta-1,5-diene iridium Chemical compound [Ir].C1CC=CCCC=C1 JJQVHODEIZDXSW-UHFFFAOYSA-N 0.000 description 1
- GZOYVTSTDWWHPD-UHFFFAOYSA-N cycloocta-1,5-diene;platinum Chemical compound [Pt].C1CC=CCCC=C1.C1CC=CCCC=C1 GZOYVTSTDWWHPD-UHFFFAOYSA-N 0.000 description 1
- HOXDXGRSZJEEKN-UHFFFAOYSA-N cycloocta-1,5-diene;rhodium Chemical compound [Rh].C1CC=CCCC=C1 HOXDXGRSZJEEKN-UHFFFAOYSA-N 0.000 description 1
- 239000004914 cyclooctane Substances 0.000 description 1
- HOODBSYIVKQTSP-UHFFFAOYSA-N cyclooctene iridium Chemical compound [Ir].[Ir].C1=CCCCCCC1 HOODBSYIVKQTSP-UHFFFAOYSA-N 0.000 description 1
- UPQZOUHVTJNGFK-UHFFFAOYSA-N diethyl 2-methylpropanedioate Chemical compound CCOC(=O)C(C)C(=O)OCC UPQZOUHVTJNGFK-UHFFFAOYSA-N 0.000 description 1
- UCQFCFPECQILOL-UHFFFAOYSA-N diethyl hydrogen phosphate Chemical group CCOP(O)(=O)OCC UCQFCFPECQILOL-UHFFFAOYSA-N 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 1
- JGMYOSNETXAAMT-UHFFFAOYSA-L dipotassium;benzenesulfonate Chemical compound [K+].[K+].[O-]S(=O)(=O)C1=CC=CC=C1.[O-]S(=O)(=O)C1=CC=CC=C1 JGMYOSNETXAAMT-UHFFFAOYSA-L 0.000 description 1
- QVKQJEWZVQFGIY-UHFFFAOYSA-N dipropyl hydrogen phosphate Chemical group CCCOP(O)(=O)OCCC QVKQJEWZVQFGIY-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 238000007336 electrophilic substitution reaction Methods 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 1
- ZXBGJDZWJJFFQY-UHFFFAOYSA-N ethyl 2-nitropropanoate Chemical compound CCOC(=O)C(C)[N+]([O-])=O ZXBGJDZWJJFFQY-UHFFFAOYSA-N 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- YDZCHDQXPLJVBG-UHFFFAOYSA-N hex-1-enyl acetate Chemical compound CCCCC=COC(C)=O YDZCHDQXPLJVBG-UHFFFAOYSA-N 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 238000007037 hydroformylation reaction Methods 0.000 description 1
- 150000002503 iridium Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- YHLVIDQQTOMBGN-UHFFFAOYSA-N methyl prop-2-enyl carbonate Chemical compound COC(=O)OCC=C YHLVIDQQTOMBGN-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- SGNSAMGUMVFALJ-UHFFFAOYSA-N n,n'-dichloroethane-1,2-diamine Chemical compound ClNCCNCl SGNSAMGUMVFALJ-UHFFFAOYSA-N 0.000 description 1
- DAZXVJBJRMWXJP-UHFFFAOYSA-N n,n-dimethylethylamine Chemical group CCN(C)C DAZXVJBJRMWXJP-UHFFFAOYSA-N 0.000 description 1
- 150000002815 nickel Chemical class 0.000 description 1
- 230000000802 nitrating effect Effects 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 150000002940 palladium Chemical class 0.000 description 1
- PENAXHPKEVTBLF-UHFFFAOYSA-L palladium(2+);prop-1-ene;dichloride Chemical compound [Pd+]Cl.[Pd+]Cl.[CH2-]C=C.[CH2-]C=C PENAXHPKEVTBLF-UHFFFAOYSA-L 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- JKDRQYIYVJVOPF-FDGPNNRMSA-L palladium(ii) acetylacetonate Chemical compound [Pd+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O JKDRQYIYVJVOPF-FDGPNNRMSA-L 0.000 description 1
- 125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
- REJGOFYVRVIODZ-UHFFFAOYSA-N phosphanium;chloride Chemical compound P.Cl REJGOFYVRVIODZ-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000004714 phosphonium salts Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 150000003057 platinum Chemical class 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- SVOOVMQUISJERI-UHFFFAOYSA-K rhodium(3+);triacetate Chemical compound [Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O SVOOVMQUISJERI-UHFFFAOYSA-K 0.000 description 1
- SONJTKJMTWTJCT-UHFFFAOYSA-K rhodium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Rh+3] SONJTKJMTWTJCT-UHFFFAOYSA-K 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- LOCKDMJLLDIFLY-UHFFFAOYSA-M sodium;2-diphenylphosphanylbenzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 LOCKDMJLLDIFLY-UHFFFAOYSA-M 0.000 description 1
- KSMWLICLECSXMI-UHFFFAOYSA-N sodium;benzene Chemical compound [Na+].C1=CC=[C-]C=C1 KSMWLICLECSXMI-UHFFFAOYSA-N 0.000 description 1
- 239000011949 solid catalyst Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- FAGLEPBREOXSAC-UHFFFAOYSA-N tert-butyl isocyanide Chemical compound CC(C)(C)[N+]#[C-] FAGLEPBREOXSAC-UHFFFAOYSA-N 0.000 description 1
- GATVZVWABXPTPF-UHFFFAOYSA-M triethyl(prop-2-enyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC=C GATVZVWABXPTPF-UHFFFAOYSA-M 0.000 description 1
- IQJPRMIQVVYNGO-UHFFFAOYSA-M trimethyl(3-phenylprop-2-enyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC=CC1=CC=CC=C1 IQJPRMIQVVYNGO-UHFFFAOYSA-M 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical group CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Images
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
- Y02P20/584—Recycling of catalysts
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- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
本発明は、マイクロリアクタを用い、水性媒体中で接触反応を行って有機化合物を製造する際に、使用済の触媒を簡単に回収することができ、かつ高収率で目的化合物を得ることができる新規な方法に関するものである。 In the present invention, when producing an organic compound by performing a catalytic reaction in an aqueous medium using a microreactor, a used catalyst can be easily recovered and a target compound can be obtained in a high yield. It relates to a new method.
医薬品の合成中間体のようなファインケミカルズは、複雑な構造を有するため、固体触媒を用いて製造するのは不適当であり、より緩和な条件下で、高い活性と選択性を示す分子触媒を用いる方法が望ましいが、一般に分子触媒については、使用後に反応混合物から分離するのに、蒸留、再結晶などの操作を繰り返し行うことが必要であり、煩雑なことが難点とされている。 Fine chemicals such as pharmaceutical synthesis intermediates have complex structures and are therefore unsuitable for production using solid catalysts, and use molecular catalysts that exhibit high activity and selectivity under milder conditions. Although a method is desirable, in general, molecular catalysts require repeated operations such as distillation and recrystallization to be separated from the reaction mixture after use, and are troublesome.
ところで、水を反応媒体とする２相反応系は、有機溶媒を用いる均一反応系に比べ、安全で環境汚染を伴わない上に、使用後の触媒分離が容易でエネルギー消費量が少ないという利点を有することから、プロピレンのヒドロホルミル化によるアルデヒドの製造や、ブタジエンの水和二量化によるオクタジエノールの製造に利用されている。 By the way, the two-phase reaction system using water as a reaction medium is advantageous in that it is safe and free from environmental pollution, and can be easily separated after use, and consumes less energy, compared to a homogeneous reaction system using an organic solvent. Therefore, it is used for production of aldehyde by hydroformylation of propylene and production of octadienol by hydration dimerization of butadiene.
しかしながら、これらの方法は、いずれも水に対する溶解度が大きい低分子化合物を用いた場合であり、水に対する溶解度が小さい原料化合物を用いた場合には、原料化合物の水への拡散が律速条件となり、反応速度が低下するのを免れない。そのため、十分な収率を得るには、高温又は長時間反応させることが必要な上に、界面活性剤のような反応促進剤を添加させなければならないが、この場合には有機相と水相が分離しにくくなるという欠点がある。 However, each of these methods is a case where a low molecular compound having a high solubility in water is used, and when a raw material compound having a low solubility in water is used, diffusion of the raw material compound into water becomes a rate-limiting condition, The reaction rate is inevitable. Therefore, in order to obtain a sufficient yield, it is necessary to react at a high temperature or for a long time, and a reaction accelerator such as a surfactant must be added. In this case, an organic phase and an aqueous phase are added. Has the disadvantage of becoming difficult to separate.
例えば、遷移金属触媒を用いてアリル位アルキル化させる反応においては、水に溶解しにくい原料化合物の場合、反応は進行しにくいので、界面活性剤を添加したり（非特許文献１、２参照）、水混和性有機溶媒を共存させる（非特許文献３、４参照）などにより反応を促進させる方法が試みられているが、これらの方法では使用済触媒の回収、再利用ができない。 For example, in a reaction in which allylic alkylation is performed using a transition metal catalyst, in the case of a raw material compound that is difficult to dissolve in water, the reaction does not proceed easily, so a surfactant may be added (see Non-Patent Documents 1 and 2). Attempts have been made to promote the reaction by coexisting a water-miscible organic solvent (see Non-Patent Documents 3 and 4), but these methods cannot recover and reuse the spent catalyst.
他方、マイクロリアクタを利用してベンゼンをニトロ化する方法も知られており、工業的連続反応と同等の反応速度で進行することが報告されているが（非特許文献５参照）、遷移金属触媒を用い、反応終了後これを回収し、再利用することについては、全く言及されていない。 On the other hand, a method of nitrating benzene using a microreactor is also known, and it has been reported that it proceeds at a reaction rate equivalent to an industrial continuous reaction (see Non-Patent Document 5). No mention is made of using and recovering and reusing it after completion of the reaction.
本発明は、このような事情に鑑み、マイクロリアクタを用い、水性媒体中、遷移金属触媒の存在下で反応を行わせ、有機化合物を製造する際に、使用済の触媒を簡単に回収、再利用することができる上に、高収率で所望の化合物を得ることができる方法を提供することを目的としてなされたものである。 In view of such circumstances, the present invention uses a microreactor to perform a reaction in an aqueous medium in the presence of a transition metal catalyst to easily collect and reuse a used catalyst when producing an organic compound. In addition, the present invention has been made for the purpose of providing a method capable of obtaining a desired compound in a high yield.
本発明者らは、マイクロリアクタ中での接触反応について種々研究を重ねた結果、水性媒体中、遷移金属触媒の存在下で反応させれば、生成物は有機相中に含まれるため水相中の触媒が簡単に分離し得ることを見出し、この知見に基づいて本発明をなすに至った。 As a result of various studies on the catalytic reaction in the microreactor, the present inventors have found that if the reaction is carried out in an aqueous medium in the presence of a transition metal catalyst, the product is contained in the organic phase, and thus in the aqueous phase. It has been found that the catalyst can be easily separated, and the present invention has been made based on this finding.
すなわち、本発明は、チューブ状マイクロリアクタ中で、遷移金属錯体と水溶性配位子からなる触媒を含有する水性媒体と有機化合物原料とを接触させて反応させたのち、触媒含有水性媒体を有機相から分離し、触媒として再利用することを特徴とする有機化合物の製造方法を提供するものである。 That is, the present invention is a tubular microreactor in which an aqueous medium containing a catalyst composed of a transition metal complex and a water-soluble ligand is brought into contact with an organic compound raw material and reacted, and then the catalyst-containing aqueous medium is converted into an organic phase. The method for producing an organic compound is characterized in that it is separated from the above and reused as a catalyst.
本発明方法のチューブ状マイクロリアクタは、金属、ガラス、プラスチック、セラミックスなどの材料で作製される。また、チューブ状マイクロリアクタの形状は、コイル状のものでもよいし、板に細い溝を刻んだものでもよい。このチューブ状マイクロリアクタの直径は細ければ細いほど効率はよいが、あまり細すぎると加工がしにくくなるので、通常は１μｍないし５ｍｍ、好ましくは１０μｍ〜２ｍｍの範囲で選ばれる。その長さには特に制限はないが、通常１ｃｍ〜５００ｍ、好ましくは５ｃｍ〜３００ｍの範囲が用いられる。 The tubular microreactor of the method of the present invention is made of a material such as metal, glass, plastic, or ceramic. Further, the shape of the tube-shaped microreactor may be a coil shape, or may be a plate in which a thin groove is cut. The smaller the diameter of this tube-shaped microreactor, the better the efficiency. However, if it is too thin, it becomes difficult to process. Therefore, it is usually selected in the range of 1 to 5 mm, preferably 10 to 2 mm. Although there is no restriction | limiting in particular in the length, Usually, 1 cm-500 m, Preferably the range of 5 cm-300 m is used.
本発明で用いられる遷移金属触媒には、遷移金属の錯体及びその金属塩、及びホモ又はヘテロ複核錯体がある。この遷移金属としては後周期遷移金属、好ましくはニッケル、パラジウム、白金、ロジウム、イリジウムがある。 Transition metal catalysts used in the present invention include transition metal complexes and metal salts thereof, and homo- or hetero-binuclear complexes. This transition metal is a late transition metal, preferably nickel, palladium, platinum, rhodium or iridium.
この遷移金属錯体としては、水溶性配位子を含むもの又はテトラヒドロフラン、ベンゼン、クロロホルム、水のような汎用溶媒が溶媒和した錯体が用いられる。 As the transition metal complex, a complex containing a water-soluble ligand or a complex solvated with a general-purpose solvent such as tetrahydrofuran, benzene, chloroform or water is used.
上記の水溶性配位子は、一般的な親水基を有するリン配位子、窒素配位子などであり、親水基とはカルボン酸塩、スルホン酸塩、硫酸エステル塩、リン酸エステル塩、ホスホン酸塩、アミン塩、アンモニウム塩、ピリジニウム塩、スルホニウム塩、ホスホニウム塩、ポリエチレンアミン、ポリエチレングリコール、多価アルコールなどである。 The water-soluble ligand is a phosphorus ligand having a general hydrophilic group, a nitrogen ligand, etc., and the hydrophilic group is a carboxylate, sulfonate, sulfate ester salt, phosphate ester salt, Phosphonates, amine salts, ammonium salts, pyridinium salts, sulfonium salts, phosphonium salts, polyethylene amines, polyethylene glycols, polyhydric alcohols, and the like.
これらの水溶性配位子としては、例えばジフェニルホスフィノ安息香酸ナトリウム塩、ホスフィニジントリス（ベンゼンスルホン酸）ナトリウム塩、（フェニルホスフィニジン）ビス（ベンゼンスルホン酸）カリウム塩、１，２‐ビス（ジ‐４‐スルホナトフェニルホスフィノ）ベンゼンナトリウム塩、トリピリジニウムホスフィン塩酸塩、トリス（ホスホナトフェニル）ホスフィンナトリウム塩、トリス（トリメチルアンモニオエチル）ホスフィントリクロリド、トリス（メトキシジエチレングリコキシエチル）ホスフィン、トリス（メトキシドデカエチレングリコキシフェニル）ホスフィン、グルコピラノシルジ（ジフェニルホスフィノ）グルコピラノシド、ビピリジンジスルホン酸ナトリウム、メチレンビス（ジフェニルオキサゾリン）テトラスルホン酸ナトリウム塩などがある。 Examples of these water-soluble ligands include diphenylphosphinobenzoic acid sodium salt, phosphinidine tris (benzenesulfonic acid) sodium salt, (phenylphosphinidin) bis (benzenesulfonic acid) potassium salt, 1,2- Bis (di-4-sulfonatophenylphosphino) benzene sodium salt, tripyridinium phosphine hydrochloride, tris (phosphonatophenyl) phosphine sodium salt, tris (trimethylammonioethyl) phosphine trichloride, tris (methoxydiethyleneglycoxyethyl) Phosphine, tris (methododecaethyleneglycoxyphenyl) phosphine, glucopyranosyldi (diphenylphosphino) glucopyranoside, sodium bipyridinedisulfonate, methylenebis (diphenyloxazoline) Tetrasodium sulfonate and the like.
本発明で用いられる遷移金属錯体としては、例えばテトラカルボニルニッケル、ビス（１，５‐シクロオクタジエン）ニッケル、ジカルボニルビス（トリフェニルホスフィン）ニッケルなどのニッケル錯体、アリルクロロパラジウムダイマー、酢酸パラジウム、ビス（１，５‐シクロオクタジエン）パラジウム、トリス（ジベンジリデンアセトン）ジパラジウム、ビス（ジベンジリデンアセトン）パラジウム、アリル（シクロペンタジエニル）パラジウム、ビス（アセチルアセトナト）パラジウム、ビス（トリフェニルホスフィン）ジクロロパラジウム、エチレンビス（トリフェニルホスフィン）パラジウム、ビス（ｔ‐ブチルイソシアニド）ジメチルパラジウム、ビス（１，１，３，３‐テトラメチルブチルイソシアニド）ジメチルパラジウム、ジネオペンチル（２，２´‐ビピリジル）パラジウム、ジクロロエチレンジアミンパラジウム、塩化パラジウムなどのパラジウム錯体、ビス（１，５‐シクロオクタジエン）白金、ビス（ジベンジリデンアセトン）白金、アリル（シクロペンタジエニル）白金、ジクロロビス（ベンゾニトリル）白金、ジクロロ（１，５‐シクロペンタジエニル）白金、塩化白金酸カリウムなどの白金錯体、三塩化ロジウム、酢酸ロジウム、トリス（アセチルアセトナト）ロジウム、（アセチルアセトナト）ジカルボニルロジウム、（アセチルアセトナト）（１，５‐シクロオクタジエン）ロジウム、（アセチルアセトナト）（ビシクロ［２．２．１］ヘプタ‐２，５‐ジエン）ロジウム、テトラカルボニルジ‐μ‐クロロジロジウム、クロロ（１，５‐シクロオクタジエン）ロジウムダイマー、ビス（ビシクロ［２．２．１］ヘプタ‐２，５‐ジエン）クロロロジウムダイマー、クロロビス（シクロオクテン）ロジウムダイマー、μ‐ジクロロテトラエチレンジロジウム、ドデカカルボニル四ロジウム、ヘキサデカカルボニル六ロジウム、ヒドリドテトラカルボニルロジウムなどのロジウム錯体、ドデカカルボニルヒドリド四イリジウム、ヘキサデカカルボニル六イリジウム、クロロトリカルボニルイリジウム、ジ‐μ‐クロロテトラキス（シクロオクテン）二イリジウム、ジ‐μ‐クロロテトラキス（エチレン）二イリジウム、ジ‐μ‐クロロビス（１，５‐シクロオクタジエン）二イリジウム、（アセチルアセトナト）（１，５‐シクロオクタジエン）イリジウム、ビス（１，５‐シクロオクタジエン）イリジウムテトラフルオロボラートなどのイリジウム錯体が挙げられる。 Examples of the transition metal complex used in the present invention include nickel complexes such as tetracarbonylnickel, bis (1,5-cyclooctadiene) nickel, dicarbonylbis (triphenylphosphine) nickel, allylchloropalladium dimer, palladium acetate, Bis (1,5-cyclooctadiene) palladium, tris (dibenzylideneacetone) dipalladium, bis (dibenzylideneacetone) palladium, allyl (cyclopentadienyl) palladium, bis (acetylacetonato) palladium, bis (triphenyl) Phosphine) dichloropalladium, ethylenebis (triphenylphosphine) palladium, bis (t-butylisocyanide) dimethylpalladium, bis (1,1,3,3-tetramethylbutylisocyanide) dimethylparadi , Dineopentyl (2,2'-bipyridyl) palladium, dichloroethylenediamine palladium, palladium chloride and other palladium complexes, bis (1,5-cyclooctadiene) platinum, bis (dibenzylideneacetone) platinum, allyl (cyclopentadienyl) ) Platinum, dichlorobis (benzonitrile) platinum, dichloro (1,5-cyclopentadienyl) platinum, platinum complexes such as potassium chloroplatinate, rhodium trichloride, rhodium acetate, tris (acetylacetonato) rhodium, (acetylacetate) Nato) dicarbonylrhodium, (acetylacetonato) (1,5-cyclooctadiene) rhodium, (acetylacetonato) (bicyclo [2.2.1] hepta-2,5-diene) rhodium, tetracarbonyldi- μ-Chlorodirhodium, Chloro (1,5- Crooctadiene) rhodium dimer, bis (bicyclo [2.2.1] hepta-2,5-diene) chlororhodium dimer, chlorobis (cyclooctene) rhodium dimer, μ-dichlorotetraethylenedirhodium, dodecacarbonyltetrarhodium, Rhodium complexes such as hexadecacarbonyl hexarhodium and hydridotetracarbonyl rhodium, dodecacarbonyl hydride tetrairidium, hexadecacarbonyl hexairidium, chlorotricarbonyliridium, di-μ-chlorotetrakis (cyclooctene) diiridium, di-μ-chloro Tetrakis (ethylene) diiridium, di-μ-chlorobis (1,5-cyclooctadiene) diiridium, (acetylacetonato) (1,5-cyclooctadiene) iridium, bis (1,5-cyclooctane) Tadiene) iridium complexes such as iridium tetrafluoroborate.
本発明方法は、アリル位アルキル化反応に代表される求核置換反応を利用する方法や、交差カップリング反応、求電子置換反応、付加反応、脱離反応など均一系触媒反応を利用する方法全般に適用することができる。 The method of the present invention is a general method using a nucleophilic substitution reaction typified by an allylic alkylation reaction or a method using a homogeneous catalytic reaction such as a cross-coupling reaction, an electrophilic substitution reaction, an addition reaction, or an elimination reaction. Can be applied to.
そして、例えば、アリル位アルキル化反応を利用する場合の原料としては、一般式
で表わされる求核剤と、一般式
で表わされる化合物の組合せであり、得られる有機化合物が、一般式
で表わされるアリル化合物との組合せを挙げることができる。
And, for example, as a raw material when using an allylic alkylation reaction, the general formula
A nucleophile represented by the general formula
A combination of compounds represented by the formula:
The combination with the allyl compound represented by these can be mentioned.
上記一般式（Ｉ）中、Ｘ及びＹは、カルボニル基、スルホニル基、ニトロ基、ニトロソ基又はシアノ基などの電子吸引基を示す。このカルボニル基は、アルキル基、アリール基、アラルキル基、アリル基、アルコキシ基、アリールオキシ基などを置換基として有することができる。 In said general formula (I), X and Y show electron withdrawing groups, such as a carbonyl group, a sulfonyl group, a nitro group, a nitroso group, or a cyano group. The carbonyl group can have an alkyl group, an aryl group, an aralkyl group, an allyl group, an alkoxy group, an aryloxy group, or the like as a substituent.
カルボニル基の具体例としては、例えばアセチル基、ベンゾイル基、シンナモイル基、エトキシカルボニル基、プロピルオキシカルボニル基、ブチルオキシカルボニル基、ペンチルオキシカルボニル基、フェノキシカルボニル基などが挙げられる。
また、スルホニル基の例としては、メタンスルホニル基、トリフルオロメタンスルホニル基、ベンゼンスルホニル基、トルエンスルホニル基などが挙げられる。
Specific examples of the carbonyl group include an acetyl group, a benzoyl group, a cinnamoyl group, an ethoxycarbonyl group, a propyloxycarbonyl group, a butyloxycarbonyl group, a pentyloxycarbonyl group, and a phenoxycarbonyl group.
Examples of the sulfonyl group include a methanesulfonyl group, a trifluoromethanesulfonyl group, a benzenesulfonyl group, and a toluenesulfonyl group.
上記一般式（Ｉ）及び（ＩＩ）中、Ｒ1とＲ2は、アルキル基、アリール基、アラルキル基、アリル基、アルコキシ基、アリールオキシ基又は水素原子である。このアルキル基には、鎖状若しくは環状のいずれもが包含される。アルキル基の炭素数は１〜１５、好ましくは１〜１０である。アルキル基の例としては、例えば、メチル基、エチル基、ブチル基、ペンチル基、ヘキシル基、オクチル基、シクロヘキシル基などが挙げられる。 In the general formulas (I) and (II), R 1 and R 2 are an alkyl group, an aryl group, an aralkyl group, an allyl group, an alkoxy group, an aryloxy group, or a hydrogen atom. This alkyl group includes a chain or a ring. The alkyl group has 1 to 15 carbon atoms, preferably 1 to 10 carbon atoms. Examples of the alkyl group include a methyl group, an ethyl group, a butyl group, a pentyl group, a hexyl group, an octyl group, and a cyclohexyl group.
上記のアリール基には、炭素環からなるアリール基及び複素環からなるアリール基の両方が包含される。この場合、炭素環としては、ベンゼン環やビフェニル環の他、ナフタレン環、インデン環、アントラセン環、フェナントレン環などの縮合環が挙げられる。一方複素環としては、フラン、チオフェン、オキサゾール、チアゾールなどの五員環や、ピリジン、ピリダジン、ピリミジン、ピラジンなどの六員環などが挙げられる。 The aryl group includes both an aryl group consisting of a carbocycle and an aryl group consisting of a heterocycle. In this case, examples of the carbocyclic ring include condensed rings such as a naphthalene ring, an indene ring, an anthracene ring, and a phenanthrene ring in addition to a benzene ring and a biphenyl ring. On the other hand, examples of the heterocyclic ring include five-membered rings such as furan, thiophene, oxazole, and thiazole, and six-membered rings such as pyridine, pyridazine, pyrimidine, and pyrazine.
また、この芳香族環は、各種の置換基を有していてもよい。このような置換基としては、酸素原子、窒素原子、ケイ素原子、ハロゲン原子などのヘテロ原子を含む各種のもの、例えばメトキシ基、ジメチルアミノ基、トリメチルシリル基、トリフルオロメチル基、塩素、フッ素などが挙げられる。アリール基の例としては、例えばフェニル基、トリル基、ジメチルアミノフェニル基、アニシル基、クロロフェニル基、フルオロフェニル基、トリフルオロメチルフェニル基、ナフチル基、ピリジル基、フリル基などが挙げられる。 Moreover, this aromatic ring may have various substituents. Examples of such substituents include various types containing heteroatoms such as oxygen atom, nitrogen atom, silicon atom, and halogen atom, such as methoxy group, dimethylamino group, trimethylsilyl group, trifluoromethyl group, chlorine, and fluorine. Can be mentioned. Examples of the aryl group include a phenyl group, tolyl group, dimethylaminophenyl group, anisyl group, chlorophenyl group, fluorophenyl group, trifluoromethylphenyl group, naphthyl group, pyridyl group, and furyl group.
上記のアラルキル基には、ベンジル基、フェニルエチル基などがある。またアリル基には未置換、一置換、二置換、環状のものが含まれ、具体的にはアリル基、ヘキセニル基、クロチル基、シンナミル基、シクロヘキセニル基などが挙げられる。また、アルコキシ基、アリーロキシ基は炭素数が１〜１０を有するものであり、酸素原子、窒素原子、ケイ素原子、ハロゲン原子などのヘテロ原子を含む各種の置換基を有していてもよい。このようなアルコキシ基、アリールオキシ基の例としては、メトキシ基、エトキシ基、プロポキシ基、ブトキシ基、ペントキシ基、ヘキシルオキシ基、フェノキシ基、メチルフェニルオキシ基、ブチルフェニルオキシ基、フルオロフェニルオキシ基などが挙げられる。 Examples of the aralkyl group include a benzyl group and a phenylethyl group. The allyl group includes unsubstituted, monosubstituted, disubstituted, and cyclic groups, and specific examples include an allyl group, a hexenyl group, a crotyl group, a cinnamyl group, and a cyclohexenyl group. Moreover, an alkoxy group and an aryloxy group have 1 to 10 carbon atoms, and may have various substituents containing a hetero atom such as an oxygen atom, a nitrogen atom, a silicon atom, or a halogen atom. Examples of such alkoxy groups and aryloxy groups include methoxy group, ethoxy group, propoxy group, butoxy group, pentoxy group, hexyloxy group, phenoxy group, methylphenyloxy group, butylphenyloxy group, fluorophenyloxy group Etc.
また、Ｒ1、Ｘ及びＹの中の２個がたがいに連結して環を形成する場合の例としては、Ｒ1、Ｘ及びＹの中の２個がたがいに連結し、それらが結合している炭素原子とともに、シクロブタン環、シクロペンタン環、フェニレンシクロプロパン環、フェニレンシクロブタン環、オキサシクロブタン環、テトラヒドロフラン環、ジオキサン環、２，６‐ジオキサシクロヘキサン環、あるいはこれらの環構成原子の１個又は２個が硫黄原子に置き換わった環などを形成する場合を挙げることができる。 In addition, as an example of the case where two of R 1 , X and Y are connected to each other to form a ring, two of R 1 , X and Y are connected to each other and they are bonded. Together with the carbon atoms present, a cyclobutane ring, cyclopentane ring, phenylenecyclopropane ring, phenylenecyclobutane ring, oxacyclobutane ring, tetrahydrofuran ring, dioxane ring, 2,6-dioxacyclohexane ring, or one of these ring atoms Or the case where the ring etc. which two replaced the sulfur atom is formed can be mentioned.
他方、上記一般式（ＩＩ）中のＺは、炭酸エステル基、カルバモイルオキシ基、リン酸基、スルホニル基、トリアルキルアンモニウム基、アセトキシ基、フェノキシ基、ニトロ基、シアノ基、水酸基又はハロゲン原子を示す。この炭酸エステル基は、低級アルコキシ基又はアリールオキシ基を置換基としてもつものであり、低級アルコキシ基とは炭素数６以下のアルコキシ基を示し、アリールオキシ基はＲ1で例示したアルキル基、アリール基、アラルキル基、アリル基、アルコキシ基、アリールオキシを置換基に有していてもよい。 On the other hand, Z in the general formula (II) represents a carbonate group, carbamoyloxy group, phosphate group, sulfonyl group, trialkylammonium group, acetoxy group, phenoxy group, nitro group, cyano group, hydroxyl group or halogen atom. Show. This carbonate group has a lower alkoxy group or an aryloxy group as a substituent, the lower alkoxy group means an alkoxy group having 6 or less carbon atoms, and the aryloxy group is an alkyl group or aryl exemplified for R 1 A group, an aralkyl group, an allyl group, an alkoxy group, or aryloxy may be present as a substituent.
炭酸エステル基として具体的には、メトキシカルボニルオキシ基、エトキシカルボニルオキシ基、プロピルオキシカルボニルオキシ基、アリルオキシカルボニルオキシ基、ヘキセニルオキシカルボニルオキシ基、シンナミルオキシカルボニルオキシ基などである。 Specific examples of the carbonate group include a methoxycarbonyloxy group, an ethoxycarbonyloxy group, a propyloxycarbonyloxy group, an allyloxycarbonyloxy group, a hexenyloxycarbonyloxy group, and a cinnamyloxycarbonyloxy group.
また、カルバモイルオキシ基及びリン酸基は、置換及び無置換のものが包含される。具体的には、カルバモイルオキシ基としてアミノカルボニルオキシ基、ジメチルアミノカルボニルオキシ基などが、リン酸基としてリン酸基、ジメチルリン酸基、ジエチルリン酸基、ジプロピルリン酸基などが挙げられる。 The carbamoyloxy group and the phosphate group include substituted and unsubstituted groups. Specifically, examples of the carbamoyloxy group include an aminocarbonyloxy group and a dimethylaminocarbonyloxy group, and examples of the phosphate group include a phosphate group, a dimethyl phosphate group, a diethyl phosphate group, and a dipropyl phosphate group.
スルホニル基及びトリアルキルアンモニウム基として具体的には、メタンスルホニル基、トリフルオロメタンスルホニル基、ベンゼンスルホニル基、トルエンスルホニル基、トリメチルアンモニウム基、トリエチルアンモニウム基、ジメチルエチルアンモニウム基などが挙げられる。 Specific examples of the sulfonyl group and trialkylammonium group include a methanesulfonyl group, a trifluoromethanesulfonyl group, a benzenesulfonyl group, a toluenesulfonyl group, a trimethylammonium group, a triethylammonium group, and a dimethylethylammonium group.
上記の一般式（Ｉ）で表わされる求核剤として、特に好ましいものは、一般式
で表わされる化合物であり、これと組み合わせて用いられるアリル化合物として、特に好ましいものは、一般式
で表わされるアリル化合物である。
As the nucleophile represented by the above general formula (I), particularly preferred are those represented by the general formula
Particularly preferred as the allyl compound used in combination with the compound represented by the general formula:
It is an allyl compound represented by these.
上記一般式（ＩＶ）中、Ｒ1、Ｒ3及びＲ4は、アルキル基、アリール基、アラルキル基、アリル基、アルコキシ基、アリールオキシ基又は水素原子であり、これらは、たがいに結合して環を形成していてもよい。このアルキル基には、鎖状若しくは環状のいずれもが包含される。アルキル基の炭素数は１〜１５、好ましくは１〜１０である。アルキル基の例としては、例えば、メチル基、エチル基、ブチル基、ペンチル基、ヘキシル基、オクチル基、シクロヘキシル基などが挙げられる。 In the general formula (IV), R 1 , R 3 and R 4 are an alkyl group, an aryl group, an aralkyl group, an allyl group, an alkoxy group, an aryloxy group or a hydrogen atom, and these are bonded to each other. A ring may be formed. This alkyl group includes a chain or a ring. The alkyl group has 1 to 15 carbon atoms, preferably 1 to 10 carbon atoms. Examples of the alkyl group include a methyl group, an ethyl group, a butyl group, a pentyl group, a hexyl group, an octyl group, and a cyclohexyl group.
上記のアリール基には、炭素環からなるアリール基及び複素環からなるアリール基の両方が包含される。この場合、炭素環としては、ベンゼン環やビフェニル環の他、ナフタレン環、インデン環、アントラセン環、フェナントレン環などの縮合環が挙げられる。一方複素環としては、フラン、チオフェン、オキサゾール、チアゾールなどの五員環や、ピリジン、ピリダジン、ピリミジン、ピラジンなどの六員環などが挙げられる。 The aryl group includes both an aryl group consisting of a carbocycle and an aryl group consisting of a heterocycle. In this case, examples of the carbocyclic ring include condensed rings such as a naphthalene ring, an indene ring, an anthracene ring, and a phenanthrene ring in addition to a benzene ring and a biphenyl ring. On the other hand, examples of the heterocyclic ring include five-membered rings such as furan, thiophene, oxazole, and thiazole, and six-membered rings such as pyridine, pyridazine, pyrimidine, and pyrazine.
また、この芳香族環は、各種の置換基を有していてもよい。このような置換基としては、酸素原子、窒素原子、ケイ素原子、ハロゲン原子などのヘテロ原子を含む各種のもの、例えばメトキシ基、ジメチルアミノ基、トリメチルシリル基、トリフルオロメチル基、塩素、フッ素などが挙げられる。アリール基の例としては、例えばフェニル基、トリル基、ジメチルアミノフェニル基、アニシル基、クロロフェニル基、フルオロフェニル基、トリフルオロメチルフェニル基、ナフチル基、ピリジル基、フリル基などが挙げられる。 Moreover, this aromatic ring may have various substituents. Examples of such substituents include various types containing heteroatoms such as oxygen atom, nitrogen atom, silicon atom, and halogen atom, such as methoxy group, dimethylamino group, trimethylsilyl group, trifluoromethyl group, chlorine, and fluorine. Can be mentioned. Examples of the aryl group include a phenyl group, tolyl group, dimethylaminophenyl group, anisyl group, chlorophenyl group, fluorophenyl group, trifluoromethylphenyl group, naphthyl group, pyridyl group, and furyl group.
上記のアラルキル基には、ベンジル基、フェニルエチル基などがある。またアリル基には未置換、一置換、二置換、環状のものが含まれ、具体的にはアリル基、ヘキセニル基、クロチル基、シンナミル基、シクロヘキセニル基などが挙げられる。また、アルコキシ基、アリーロキシ基は炭素数が１〜１０を有するものであり、酸素原子、窒素原子、ケイ素原子、ハロゲン原子などのヘテロ原子を含む各種の置換基を有していてもよい。このようなアルコキシ基、アリールオキシ基の例としては、メトキシ基、エトキシ基、プロポキシ基、ブトキシ基、ペントキシ基、ヘキシルオキシ基、フェノキシ基、メチルフェニルオキシ基、ブチルフェニルオキシ基、フルオロフェニルオキシ基などが挙げられる。 Examples of the aralkyl group include a benzyl group and a phenylethyl group. The allyl group includes unsubstituted, monosubstituted, disubstituted, and cyclic groups, and specific examples include an allyl group, a hexenyl group, a crotyl group, a cinnamyl group, and a cyclohexenyl group. Moreover, an alkoxy group and an aryloxy group have 1 to 10 carbon atoms, and may have various substituents containing a hetero atom such as an oxygen atom, a nitrogen atom, a silicon atom, or a halogen atom. Examples of such alkoxy groups and aryloxy groups include methoxy group, ethoxy group, propoxy group, butoxy group, pentoxy group, hexyloxy group, phenoxy group, methylphenyloxy group, butylphenyloxy group, fluorophenyloxy group Etc.
また、一般式（ＩＶ）において、Ｒ1、Ｒ3及びＲ4の中の２個がたがいに連結して環を形成する場合の例としては、Ｒ1とＲ3、Ｒ1とＲ4又はＲ3とＲ4がたがいに連結し、それらが結合している炭素原子とともに、シクロプロパン環、シクロブタン環、シクロペンタン環、フェニレンシクロプロパン環、フェニレンシクロブタン環、オキサシクロブタン環、テトラヒドロフラン環、ジオキサン環、２，６‐ジオキサシクロヘキサン環、フェニレン環と縮合したジオキサシクロプロピレン環などを形成する場合を挙げることができる。 In the general formula (IV), examples of the case where two of R 1 , R 3 and R 4 are linked together to form a ring include R 1 and R 3 , R 1 and R 4 or R 3 and R 4 are connected to each other, and together with the carbon atom to which they are bonded, a cyclopropane ring, cyclobutane ring, cyclopentane ring, phenylene cyclopropane ring, phenylene cyclobutane ring, oxacyclobutane ring, tetrahydrofuran ring, dioxane ring And a 2,6-dioxacyclohexane ring, a dioxacyclopropylene ring condensed with a phenylene ring, and the like.
したがって、一般式（Ｉ）で表わされる求核剤の例としては、アセト酢酸エチルエステル、アセト酢酸プロピルエステル、アセト酢酸ブチルエステル、アセト酢酸ペンチルエステル、アリルアセト酢酸エチルエステル、マロン酸ジメチルエステル、アセチルアセトン、１，３‐ジオキソシクロヘキサン、メチルマロン酸ジエチル、アセトブチロラクトン、ベンゾイルシクロヘキサノン、ベンゾイル酢酸エチルエステル、マロン酸ジエチルエステル、ニトロプロピオン酸エチルエステル、シアノ酢酸エチルエステルなどがある。 Accordingly, examples of the nucleophile represented by the general formula (I) include acetoacetic acid ethyl ester, acetoacetic acid propyl ester, acetoacetic acid butyl ester, acetoacetic acid pentyl ester, allyl acetoacetic acid ethyl ester, malonic acid dimethyl ester, acetylacetone, Examples include 1,3-dioxocyclohexane, diethyl methylmalonate, acetobutyrolactone, benzoylcyclohexanone, benzoylacetic acid ethyl ester, malonic acid diethyl ester, nitropropionic acid ethyl ester, and cyanoacetic acid ethyl ester.
また、前記一般式（Ｖ）中、Ｒ5は、アルキル基、アリール基、アラルキル基、アリル基、アルコキシ基、アリールオキシ基又は水素原子を示し、Ｒ6は、メチル基、低級アルコキシ基を示し、Ｒ5のアルキル基、アリール基、アラルキル基、アリル基、アルコキシ基、アリールオキシ基は一般式（ＩＶ）の場合と同様である。また、Ｒ6の低級アルコキシ基は炭素数が６以下のアルコキシ基であり、具体的にはメトキシ基、エトキシ基、プロポキシ基などである。また、Ｒ6のアリールオキシ基はアルキル基、アリール基、アラルキル基、アリル基、アルコキシ基、アリールオキシ基で置換されていてもよい。 In the general formula (V), R 5 represents an alkyl group, an aryl group, an aralkyl group, an allyl group, an alkoxy group, an aryloxy group or a hydrogen atom, and R 6 represents a methyl group or a lower alkoxy group. , R 5 alkyl group, aryl group, aralkyl group, allyl group, alkoxy group and aryloxy group are the same as those in formula (IV). The lower alkoxy group for R 6 is an alkoxy group having 6 or less carbon atoms, and specifically includes a methoxy group, an ethoxy group, a propoxy group, and the like. In addition, the aryloxy group of R 6 may be substituted with an alkyl group, an aryl group, an aralkyl group, an allyl group, an alkoxy group, or an aryloxy group.
したがって、一般式（ＩＩ）で表わされるアリル化合物の例としては、酢酸アリルエステル、酢酸クロチルエステル、酢酸ヘキセニルエステル、酢酸シンナミルエステル、炭酸ジアリルエステル、炭酸ジヘキセニルエステル、炭酸アリルメチルエステル、酢酸ベンジルオキシブテニルエステル、アリルブロミド、アリルクロリド、アリルアルコール、アリルジエチルリン酸エステル、ヘキセニルジメチルリン酸エステル、アリルトリエチルアンモニウムクロリド、シンナミルトリメチルアンモニウムクロリドなどがある。 Accordingly, examples of allyl compounds represented by the general formula (II) include allyl acetate, crotyl acetate, hexenyl acetate, cinnamyl acetate, diallyl carbonate, dihexenyl carbonate, allyl methyl ester, and benzyl acetate. Examples include oxybutenyl ester, allyl bromide, allyl chloride, allyl alcohol, allyl diethyl phosphate ester, hexenyl dimethyl phosphate ester, allyl triethyl ammonium chloride, cinnamyl trimethyl ammonium chloride.
前記反応を実施する場合、原料をそのまま導入してもよいが、水又は有機溶媒にあらかじめ溶解して導入してもよい。有機溶媒を用いる場合には、トルエン、キシレン、メシチレンなどの芳香族炭化水素類、ペンタン、ヘキサン、オクタンなどの脂肪族飽和炭化水素類、ジクロロメタン、クロロホルム、ジクロロエタンなどのハロゲン系溶媒類などが挙げられる。 In carrying out the reaction, the raw materials may be introduced as they are, or may be introduced after being dissolved in water or an organic solvent in advance. In the case of using an organic solvent, aromatic hydrocarbons such as toluene, xylene and mesitylene, aliphatic saturated hydrocarbons such as pentane, hexane and octane, and halogen solvents such as dichloromethane, chloroform and dichloroethane are exemplified. .
本発明で用いる原料をチューブ状の形態を有するマイクロリアクタに導入する際、原料が２種若しくはそれ以上の場合、あらかじめそれらを混合した溶液として１つの入り口から導入してもよいし、それぞれを別々の入り口から導入してもよい。また、原料の１つが水溶性である場合、触媒の溶解した水溶液にあらかじめ溶かしておいたものを用いてもよい。チューブ状マイクロリアクタに直接水相と有機相を導入してもよいが、マイクロ混合器などを配してチューブ状マイクロリアクタに導入してもよい。 When introducing the raw material used in the present invention into a microreactor having a tubular shape, when two or more raw materials are used, they may be introduced from one inlet as a solution in which they are mixed beforehand, It may be introduced from the entrance. In addition, when one of the raw materials is water-soluble, a material previously dissolved in an aqueous solution in which the catalyst is dissolved may be used. The water phase and the organic phase may be directly introduced into the tube-shaped microreactor, but may be introduced into the tube-shaped microreactor by arranging a micromixer or the like.
反応後の生成物の分離は、生成物を含む有機相を、触媒を含む水相から分離後、蒸留・再結晶などの通常の精製単離法によって容易に実施される。また、触媒を含む水相はそのまま次の反応に使用することができる。 Separation of the product after the reaction is easily carried out by an ordinary purification and isolation method such as distillation and recrystallization after separating the organic phase containing the product from the aqueous phase containing the catalyst. Moreover, the aqueous phase containing a catalyst can be used for the next reaction as it is.
本発明によると、細いチューブ状の形態を有するマイクロリアクタ中に、遷移金属錯体と水溶性配位子からなる触媒を溶かした触媒水溶液と、液体の反応原料を導入し反応させることにより、触媒の再利用可能な有機化合物の製造方法が提供される。この方法によって、水に溶けにくい反応原料を用いる合成反応も円滑に進行し、さらに触媒は相分離によって容易に回収再利用が可能になる。 According to the present invention, a catalyst aqueous solution in which a catalyst comprising a transition metal complex and a water-soluble ligand is dissolved in a microreactor having a thin tubular form and a liquid reaction raw material are introduced and reacted, whereby the catalyst is recycled. A method for producing an available organic compound is provided. By this method, a synthesis reaction using a reaction raw material that is hardly soluble in water proceeds smoothly, and the catalyst can be easily recovered and reused by phase separation.
次に実施例により、本発明を実施するための最良の形態を説明する。 Next, the best mode for carrying out the present invention will be described by way of examples.
アセト酢酸エチル（２．２ｍｏｌ／ｌ）、酢酸アリル（２．０ｍｏｌ／ｌ）及びメシチレンの混合液（Ｏ液）を調製する。同様にアリルパラジウムクロリドダイマー（０．００７５ｍｏｌ／ｌ）、ホスフィニジントリス（ベンゼンスルホン酸）トリナトリウム塩配位子（０．０６ｍｏｌ／ｌ）、炭酸カリウム（１．６５ｍｏｌ／ｌ）の水溶液（Ｗ液）を調製する。図１に示すように、それぞれの溶液を流速１ｍｌ／ｍｉｎで、９０℃の恒温槽に入った内容積４００μｌ、内径０．２５ｍｍのチューブ状マイクロリアクタに導入する。リアクタから出てきた溶液を飽和塩化アンモニウム水溶液中に滴下し反応を停止させる。反応液を定法に従って処理すると、アリルアセト酢酸エチルエステルが収率５９％で得られた。 A mixed solution (solution O) of ethyl acetoacetate (2.2 mol / l), allyl acetate (2.0 mol / l) and mesitylene is prepared. Similarly, an allyl palladium chloride dimer (0.0075 mol / l), an phosphinidin tris (benzenesulfonic acid) trisodium salt ligand (0.06 mol / l), an aqueous solution of potassium carbonate (1.65 mol / l) (W Liquid). As shown in FIG. 1, each solution is introduced at a flow rate of 1 ml / min into a tubular microreactor having an internal volume of 400 μl and an inner diameter of 0.25 mm in a thermostat at 90 ° C. The solution coming out of the reactor is dropped into a saturated aqueous ammonium chloride solution to stop the reaction. When the reaction solution was treated according to a conventional method, allyl acetoacetic acid ethyl ester was obtained in a yield of 59%.
実施例１のチューブ状マイクロリアクタの代わりに内容積４００μｌ、内径０．５０ｍｍのチューブ状マイクロリアクタを用いて反応を行った。その結果、アリルアセト酢酸エチルエステルが収率２８％で得られた。 The reaction was carried out using a tubular microreactor having an internal volume of 400 μl and an inner diameter of 0.50 mm instead of the tubular microreactor of Example 1. As a result, allyl acetoacetic acid ethyl ester was obtained in a yield of 28%.
実施例１のチューブ状マイクロリアクタの代わりに内容積４００μｌ、内径１．００ｍｍのチューブ状マイクロリアクタを用いて反応を行った。その結果、アリルアセト酢酸エチルエステルが収率１３％で得られた。 The reaction was performed using a tubular microreactor having an internal volume of 400 μl and an inner diameter of 1.00 mm instead of the tubular microreactor of Example 1. As a result, allyl acetoacetic acid ethyl ester was obtained in a yield of 13%.
比較例１
内容積５ｍｌの円錐状反応容器に実施例１のＯ液（０．２ｍｌ）とＷ液（０．２ｍｌ）を入れ、１２秒間高速撹拌（約２２００ｒｐｍ）する。この反応液に飽和塩化アンモニウム水溶液（２ｍｌ）を加え、定法により処理するとアリルアセト酢酸エチルエステルが収率７％で得られた。
Comparative Example 1
The O solution (0.2 ml) and W solution (0.2 ml) of Example 1 are placed in a conical reaction vessel having an internal volume of 5 ml and stirred at high speed (about 2200 rpm) for 12 seconds. Saturated aqueous ammonium chloride solution (2 ml) was added to this reaction solution and treated by a conventional method, whereby allyl acetoacetic acid ethyl ester was obtained in a yield of 7%.
実施例１のＯ液とＷ液をそれぞれ流速０．５ｍｌ／ｍｉｎで９０℃の恒温槽に入った内容積４００μｌ、内径０．２５ｍｍのチューブ状マイクロリアクタに導入する。リアクタから出てきた溶液を飽和塩化アンモニウム水溶液中に滴下し反応を停止させる。反応液を定法に従って処理すると、アリルアセト酢酸エチルエステルが収率７３％で得られた。 The O liquid and the W liquid of Example 1 were introduced into a tubular microreactor having an internal volume of 400 μl and an inner diameter of 0.25 mm, which was placed in a thermostat at 90 ° C. at a flow rate of 0.5 ml / min. The solution coming out of the reactor is dropped into a saturated aqueous ammonium chloride solution to stop the reaction. When the reaction solution was treated according to a conventional method, allyl acetoacetic acid ethyl ester was obtained in a yield of 73%.
実施例４のチューブ状マイクロリアクタの代わりに内容積４００μｌ、内径０．５０ｍｍのチューブ状マイクロリアクタを用いて反応を行った。その結果、アリルアセト酢酸エチルエステルが収率４１％で得られた。 The reaction was performed using a tubular microreactor having an internal volume of 400 μl and an inner diameter of 0.50 mm instead of the tubular microreactor of Example 4. As a result, allyl acetoacetic acid ethyl ester was obtained with a yield of 41%.
実施例４のチューブ状マイクロリアクタの代わりに内容積４００μｌ、内径１．００ｍｍのチューブ状マイクロリアクタを用いて反応を行った。その結果、アリルアセト酢酸エチルエステルが収率２１％で得られた。 The reaction was performed using a tubular microreactor having an internal volume of 400 μl and an inner diameter of 1.00 mm instead of the tubular microreactor of Example 4. As a result, allyl acetoacetic acid ethyl ester was obtained in a yield of 21%.
比較例２
内容積５ｍｌの円錐状反応容器に実施例１のＯ液（０．２ｍｌ）とＷ液（０．２ｍｌ）を入れ、２４秒間高速撹拌（約２２００ｒｐｍ）する。この反応液に飽和塩化アンモニウム水溶液（２ｍｌ）を加え、定法により処理するとアリルアセト酢酸エチルエステルが収率１０％で得られた。
Comparative Example 2
The O solution (0.2 ml) and W solution (0.2 ml) of Example 1 are placed in a 5 ml conical reaction vessel, and stirred at high speed (about 2200 rpm) for 24 seconds. Saturated aqueous ammonium chloride solution (2 ml) was added to this reaction solution and treated by a conventional method to obtain allyl acetoacetic acid ethyl ester in a yield of 10%.
実施例１のＯ液とＷ液をそれぞれ流速０．２５ｍｌ／ｍｉｎで９０℃の恒温槽に入った内容積４００μｌ、内径０．２５ｍｍのチューブ状マイクロリアクタに導入する。リアクタから出てきた溶液を飽和塩化アンモニウム水溶液中に滴下し反応を停止させる。反応液を定法に従って処理すると、アリルアセト酢酸エチルエステルが収率８０％で得られた。 The O liquid and the W liquid of Example 1 are introduced into a tubular microreactor having an internal volume of 400 μl and an inner diameter of 0.25 mm, respectively, in a constant temperature bath at 90 ° C. at a flow rate of 0.25 ml / min. The solution coming out of the reactor is dropped into a saturated aqueous ammonium chloride solution to stop the reaction. When the reaction solution was treated according to a conventional method, allyl acetoacetic acid ethyl ester was obtained in a yield of 80%.
実施例７のチューブ状マイクロリアクタの代わりに内容積４００μｌ、内径０．５０ｍｍのチューブ状マイクロリアクタを用いて反応を行った。その結果、アリルアセト酢酸エチルエステルが収率６１％で得られた。 The reaction was performed using a tubular microreactor having an internal volume of 400 μl and an inner diameter of 0.50 mm instead of the tubular microreactor of Example 7. As a result, allyl acetoacetic acid ethyl ester was obtained in a yield of 61%.
実施例７のチューブ状マイクロリアクタの代わりに内容積４００μｌ、内径１．００ｍｍのチューブ状マイクロリアクタを用いて反応を行った。その結果、アリルアセト酢酸エチルエステルが収率４６％で得られた。 The reaction was carried out using a tubular microreactor having an internal volume of 400 μl and an inner diameter of 1.00 mm instead of the tubular microreactor of Example 7. As a result, allyl acetoacetic acid ethyl ester was obtained with a yield of 46%.
比較例３
内容積５ｍｌの円錐状反応容器に実施例１のＯ液（０．２ｍｌ）とＷ液（０．２ｍｌ）を入れ、４８秒間高速撹拌（約２２００ｒｐｍ）する。この反応液に飽和塩化アンモニウム水溶液（２ｍｌ）を加え、定法により処理するとアリルアセト酢酸エチルエステルが収率２８％で得られた。
Comparative Example 3
The O solution (0.2 ml) and W solution (0.2 ml) of Example 1 are placed in a conical reaction vessel having an internal volume of 5 ml and stirred at high speed (about 2200 rpm) for 48 seconds. Saturated aqueous ammonium chloride solution (2 ml) was added to this reaction solution and treated by a conventional method to obtain allyl acetoacetic acid ethyl ester in 28% yield.
実施例７の９０℃の恒温槽の代わりに３０℃の高温槽を用いて反応を行ったところ、アリルアセト酢酸エチルエステルが収率２０％で得られた。 When the reaction was carried out using a 30 ° C. high temperature bath instead of the 90 ° C. constant temperature bath in Example 7, allyl acetoacetic acid ethyl ester was obtained in a yield of 20%.
実施例８の９０℃の恒温槽の代わりに３０℃の高温槽を用いて反応を行ったところ、アリルアセト酢酸エチルエステルが収率１０％で得られた。 When the reaction was carried out using a 30 ° C. high temperature bath instead of the 90 ° C. constant temperature bath of Example 8, allyl acetoacetic acid ethyl ester was obtained in a yield of 10%.
実施例９の９０℃の恒温槽の代わりに３０℃の高温槽を用いて反応を行ったところ、アリルアセト酢酸エチルエステルが収率６％で得られた。 When the reaction was carried out using a 30 ° C. high temperature bath instead of the 90 ° C. constant temperature bath of Example 9, allyl acetoacetic acid ethyl ester was obtained in a yield of 6%.
比較例４
内容積５ｍｌの円錐状反応容器に実施例１のＯ液（０．２ｍｌ）とＷ液（０．２ｍｌ）を入れ、３０℃で４８秒間高速撹拌（約２２００ｒｐｍ）する。この反応液に飽和塩化アンモニウム水溶液（２ｍｌ）を加え、定法により処理するとアリルアセト酢酸エチルエステルが収率３％で得られた。
Comparative Example 4
The O solution (0.2 ml) and W solution (0.2 ml) of Example 1 are placed in a conical reaction vessel having an internal volume of 5 ml, and high-speed stirring (about 2200 rpm) is performed at 30 ° C. for 48 seconds. Saturated aqueous ammonium chloride solution (2 ml) was added to this reaction solution and treated by a conventional method to obtain allyl acetoacetic acid ethyl ester in a yield of 3%.
実施例１のＯ液とＷ液それぞれを流速０．２５ｍｌ／ｍｉｎで、９０℃の恒温槽に入った内容積４００μｌ、内径０．２５ｍｍのチューブ状マイクロリアクタに導入する。リアクタから出てきた溶液をヘキサン中に滴下する（１回目）。二相に分かれた水相（下相）側を抜き取り、炭酸カリウムを加えた溶液とＯ液を流速０．２５ｍｌ／ｍｉｎで、９０℃の恒温槽に入った内容積４００μｌ、内径０．２５ｍｍのチューブ状マイクロリアクタに再度導入する。リアクタから出てきた溶液をヘキサン中に滴下する（２回目）。再度二相に分かれた水相（下相）側を抜き取り、炭酸カリウムを加えた溶液とＯ液を流速０．２５ｍｌ／ｍｉｎで、９０℃の恒温槽に入った内容積４００μｌ、内径０．２５ｍｍのチューブ状マイクロリアクタに再々度導入する。リアクタから出てきた溶液をヘキサン中に滴下する（３回目）。１回目、２回目、３回目で取れた有機相をそれぞれ定法にしたがって処理すると、アリルアセト酢酸エチルエステルが１回目収率８０％、２回目収率７３％、３回目収率６３％で得られた。このことから、パラジウム触媒のほとんどがリサイクルされていることが確認された。 The O liquid and the W liquid of Example 1 are introduced at a flow rate of 0.25 ml / min into a tubular microreactor having an inner volume of 400 μl and an inner diameter of 0.25 mm, which is placed in a thermostatic chamber at 90 ° C. The solution coming out of the reactor is dropped into hexane (first time). The aqueous phase (lower phase) side separated into two phases is extracted, and a solution containing potassium carbonate and O solution are flowed at a flow rate of 0.25 ml / min, an internal volume of 400 μl in an oven at 90 ° C., and an inner diameter of 0.25 mm. Re-introduce into the tubular microreactor. The solution coming out of the reactor is dropped into hexane (second time). The aqueous phase (lower phase) divided into two phases was again extracted, and a solution containing potassium carbonate and O solution were flowed at a flow rate of 0.25 ml / min, and the inner volume was 400 μl and the inner diameter was 0.25 mm. Re-introduced into the tubular microreactor. The solution coming out of the reactor is dropped into hexane (third time). When the organic phases obtained in the first, second, and third times were treated according to conventional methods, allyl acetoacetic acid ethyl ester was obtained in a first yield of 80%, a second yield of 73%, and a third yield of 63%. . From this, it was confirmed that most of the palladium catalyst was recycled.
アセト酢酸エチル（２．２ｍｏｌ／ｌ）、炭酸アリルメチル（２．０ｍｏｌ／ｌ）及びメシチレンの混合液（Ｏ1液）を調製する。同様にアリルパラジウムクロリドダイマー（０．００７５ｍｏｌ／ｌ）、ホスフィニジントリス（ベンゼンスルホン酸）トリナトリウム塩配位子（０．０６ｍｏｌ／ｌ）、炭酸カリウム（１．６５ｍｏｌ／ｌ）の水溶液（Ｗ液）を調製する。それぞれの溶液を流速０．２５ｍｌ／ｍｉｎで、９０℃の恒温槽に入った内容積４００μｌ、内径０．２５ｍｍのチューブ状マイクロリアクタに導入する。リアクタから出てきた溶液を飽和塩化アンモニウム水溶液中に滴下し反応を停止させる。反応液を定法に従って処理すると、アリルアセト酢酸エチルエステルが収率８０％で得られた。 A mixed solution (O 1 solution) of ethyl acetoacetate (2.2 mol / l), allylmethyl carbonate (2.0 mol / l) and mesitylene is prepared. Similarly, an allyl palladium chloride dimer (0.0075 mol / l), an phosphinidin tris (benzenesulfonic acid) trisodium salt ligand (0.06 mol / l), an aqueous solution of potassium carbonate (1.65 mol / l) (W Liquid). Each solution is introduced at a flow rate of 0.25 ml / min into a tubular microreactor having an internal volume of 400 μl and an inner diameter of 0.25 mm in a thermostat at 90 ° C. The solution coming out of the reactor is dropped into a saturated aqueous ammonium chloride solution to stop the reaction. When the reaction solution was treated according to a conventional method, allyl acetoacetic acid ethyl ester was obtained in a yield of 80%.
比較例５
内容積５ｍｌの円錐状反応容器に実施例１４のＯ1液（０．２ｍｌ）とＷ液（０．２ｍｌ）を入れ、４８秒間９０℃で高速撹拌（約２２００ｒｐｍ）する。この反応液に飽和塩化アンモニウム水溶液（２ｍｌ）を加え、定法により処理するとアリルアセト酢酸エチルエステルが収率１２％で得られた。
Comparative Example 5
The O 1 solution (0.2 ml) and W solution (0.2 ml) of Example 14 are placed in a conical reaction vessel having an internal volume of 5 ml, and high-speed stirring (about 2200 rpm) is performed at 90 ° C. for 48 seconds. Saturated aqueous ammonium chloride solution (2 ml) was added to this reaction solution and treated by a conventional method to obtain allyl acetoacetic acid ethyl ester in a yield of 12%.
アセト酢酸エチル（２．２ｍｏｌ／ｌ）、酢酸３‐ヘキセニルエステル（２．０ｍｏｌ／ｌ）及びメシチレンの混合液（Ｏ2液）を調製する。同様にアリルパラジウムクロリドダイマー（０．００７５ｍｏｌ／ｌ）、ホスフィニジントリス（ベンゼンスルホン酸）トリナトリウム塩配位子（０．０６ｍｏｌ／ｌ）、炭酸カリウム（１．６５ｍｏｌ／ｌ）の水溶液（Ｗ液）を調製する。それぞれの溶液を流速０．２５ｍｌ／ｍｉｎで、９０℃の恒温槽に入った内容積２０００μｌ、内径０．２５ｍｍのチューブ状マイクロリアクタに導入する。リアクタから出てきた溶液を飽和塩化アンモニウム水溶液中に滴下し反応を停止させる。反応液を定法に従って処理すると、ヘキセニルアセト酢酸エチルエステルが収率４９％で得られた。 A mixed liquid (O 2 liquid) of ethyl acetoacetate (2.2 mol / l), acetic acid 3-hexenyl ester (2.0 mol / l) and mesitylene is prepared. Similarly, an allyl palladium chloride dimer (0.0075 mol / l), an phosphinidin tris (benzenesulfonic acid) trisodium salt ligand (0.06 mol / l), an aqueous solution of potassium carbonate (1.65 mol / l) (W Liquid). Each solution is introduced at a flow rate of 0.25 ml / min into a tubular microreactor having an internal volume of 2000 μl and an inner diameter of 0.25 mm in a thermostat at 90 ° C. The solution coming out of the reactor is dropped into a saturated aqueous ammonium chloride solution to stop the reaction. When the reaction solution was treated according to a conventional method, hexenyl acetoacetic acid ethyl ester was obtained in a yield of 49%.
比較例６
内容積５ｍｌの円錐状反応容器に実施例１５のＯ2液（１．０ｍｌ）とＷ液（１．０ｍｌ）を入れ、４分間９０℃で高速撹拌（約２２００ｒｐｍ）する。この反応液に飽和塩化アンモニウム水溶液（２ｍｌ）を加え、定法により処理するとヘキセニルアセト酢酸エチルエステルが収率２％で得られた。
Comparative Example 6
The O 2 liquid (1.0 ml) and W liquid (1.0 ml) of Example 15 are placed in a conical reaction vessel having an internal volume of 5 ml, and high-speed stirring (about 2200 rpm) is performed at 90 ° C. for 4 minutes. A saturated aqueous ammonium chloride solution (2 ml) was added to the reaction solution, and the mixture was treated by a conventional method to obtain hexenyl acetoacetic acid ethyl ester in a yield of 2%.
アセト酢酸エチル（２．２ｍｏｌ／ｌ）、酢酸シンナミルエステル（２．０ｍｏｌ／ｌ）及びメシチレンの混合液（Ｏ3液）を調製する。同様にアリルパラジウムクロリドダイマー（０．００７５ｍｏｌ／ｌ）、ホスフィニジントリス（ベンゼンスルホン酸）トリナトリウム塩配位子（０．０６ｍｏｌ／ｌ）、炭酸カリウム（１．６５ｍｏｌ／ｌ）の水溶液（Ｗ液）を調製する。それぞれの溶液を流速０．２５ｍｌ／ｍｉｎで、９０℃の恒温槽に入った内容積２０００μｌ、内径０．２５ｍｍのチューブ状マイクロリアクタに導入する。リアクタから出てきた溶液を飽和塩化アンモニウム水溶液中に滴下し反応を停止させる。反応液を定法に従って処理すると、シンナミルアセト酢酸エチルエステルが収率８６％で得られた。 A mixed liquid (O 3 liquid) of ethyl acetoacetate (2.2 mol / l), acetic acid cinnamyl ester (2.0 mol / l) and mesitylene is prepared. Similarly, an allyl palladium chloride dimer (0.0075 mol / l), an phosphinidin tris (benzenesulfonic acid) trisodium salt ligand (0.06 mol / l), an aqueous solution of potassium carbonate (1.65 mol / l) (W Liquid). Each solution is introduced at a flow rate of 0.25 ml / min into a tubular microreactor having an internal volume of 2000 μl and an inner diameter of 0.25 mm in a thermostat at 90 ° C. The solution coming out of the reactor is dropped into a saturated aqueous ammonium chloride solution to stop the reaction. When the reaction solution was treated according to a conventional method, cinnamylacetoacetic acid ethyl ester was obtained in a yield of 86%.
比較例７
内容積５ｍｌの円錐状反応容器に実施例１６のＯ3液（１．０ｍｌ）とＷ液（１．０ｍｌ）を入れ、４分間９０℃で高速撹拌（約２２００ｒｐｍ）する。この反応液に飽和塩化アンモニウム水溶液（２ｍｌ）を加え、定法により処理するとシンナミルアセト酢酸エチルエステルが収率６％で得られた。
Comparative Example 7
The O 3 solution (1.0 ml) and the W solution (1.0 ml) of Example 16 are placed in a conical reaction vessel having an internal volume of 5 ml and stirred at high speed (about 2200 rpm) at 90 ° C. for 4 minutes. Saturated ammonium chloride aqueous solution (2 ml) was added to this reaction solution and treated by a conventional method to obtain cinnamylacetoacetic acid ethyl ester in a yield of 6%.
アセト酢酸プロピルエステル（２．２ｍｏｌ／ｌ）、酢酸アリルエステル（２．０ｍｏｌ／ｌ）及びメシチレンの混合液（Ｏ4液）を調製する。同様にアリルパラジウムクロリドダイマー（０．００７５ｍｏｌ／ｌ）、ホスフィニジントリス（ベンゼンスルホン酸）トリナトリウム塩配位子（０．０６ｍｏｌ／ｌ）、炭酸カリウム（１．６５ｍｏｌ／ｌ）の水溶液（Ｗ液）を調製する。それぞれの溶液を流速０．２５ｍｌ／ｍｉｎで、９０℃の恒温槽に入った内容積４００μｌ、内径０．２５ｍｍのチューブ状マイクロリアクタに導入する。リアクタから出てきた溶液を飽和塩化アンモニウム水溶液中に滴下し反応を停止させる。反応液を定法に従って処理すると、アリルアセト酢酸プロピルエステルが収率５３％で得られた。 A mixed liquid (O 4 liquid) of acetoacetic acid propyl ester (2.2 mol / l), acetic acid allyl ester (2.0 mol / l) and mesitylene is prepared. Similarly, an allyl palladium chloride dimer (0.0075 mol / l), an phosphinidin tris (benzenesulfonic acid) trisodium salt ligand (0.06 mol / l), an aqueous solution of potassium carbonate (1.65 mol / l) (W Liquid). Each solution is introduced at a flow rate of 0.25 ml / min into a tubular microreactor having an internal volume of 400 μl and an inner diameter of 0.25 mm in a thermostat at 90 ° C. The solution coming out of the reactor is dropped into a saturated aqueous ammonium chloride solution to stop the reaction. When the reaction solution was treated according to a conventional method, allylacetoacetic acid propyl ester was obtained in a yield of 53%.
比較例８
内容積５ｍｌの円錐状反応容器に実施例１７のＯ4液（０．２ｍｌ）とＷ液（０．２ｍｌ）を入れ、４８秒間９０℃で高速撹拌（約２２００ｒｐｍ）する。この反応液に飽和塩化アンモニウム水溶液（２ｍｌ）を加え、定法により処理するとアリルアセト酢酸プロピルエステルが収率１３％で得られた。
Comparative Example 8
The O 4 solution (0.2 ml) and W solution (0.2 ml) of Example 17 are placed in a conical reaction vessel having an internal volume of 5 ml, and high-speed stirring (about 2200 rpm) is performed at 90 ° C. for 48 seconds. Saturated aqueous ammonium chloride solution (2 ml) was added to this reaction solution and treated by a conventional method to obtain allyl acetoacetic acid propyl ester in a yield of 13%.
アセト酢酸ブチルエステル（２．２ｍｏｌ／ｌ）、酢酸アリルエステル（２．０ｍｏｌ／ｌ）及びメシチレンの混合液（Ｏ5液）を調製する。同様にアリルパラジウムクロリドダイマー（０．００７５ｍｏｌ／ｌ）、ホスフィニジントリス（ベンゼンスルホン酸）トリナトリウム塩配位子（０．０６ｍｏｌ／ｌ）、炭酸カリウム（１．６５ｍｏｌ／ｌ）の水溶液（Ｗ液）を調製する。それぞれの溶液を流速０．２５ｍｌ／ｍｉｎで、９０℃の恒温槽に入った内容積４００μｌ、内径０．２５ｍｍのチューブ状マイクロリアクタに導入する。リアクタから出てきた溶液を飽和塩化アンモニウム水溶液中に滴下し反応を停止させる。反応液を定法に従って処理すると、アリルアセト酢酸ブチルエステルが収率３０％で得られた。 A mixed liquid (O 5 liquid) of acetoacetic acid butyl ester (2.2 mol / l), acetic acid allyl ester (2.0 mol / l) and mesitylene is prepared. Similarly, an allyl palladium chloride dimer (0.0075 mol / l), an phosphinidin tris (benzenesulfonic acid) trisodium salt ligand (0.06 mol / l), an aqueous solution of potassium carbonate (1.65 mol / l) (W Liquid). Each solution is introduced at a flow rate of 0.25 ml / min into a tubular microreactor having an internal volume of 400 μl and an inner diameter of 0.25 mm in a thermostat at 90 ° C. The solution coming out of the reactor is dropped into a saturated aqueous ammonium chloride solution to stop the reaction. When the reaction solution was treated according to a conventional method, allyl acetoacetic acid butyl ester was obtained in a yield of 30%.
比較例９
内容積５ｍｌの円錐状反応容器に実施例１８のＯ5液（０．２ｍｌ）とＷ液（０．２ｍｌ）を入れ、４８秒間９０℃で高速撹拌（約２２００ｒｐｍ）する。この反応液に飽和塩化アンモニウム水溶液（２ｍｌ）を加え、定法により処理するとアリルアセト酢酸ブチルエステルが収率４％で得られた。
Comparative Example 9
The O 5 solution (0.2 ml) and W solution (0.2 ml) of Example 18 are placed in a conical reaction vessel having an internal volume of 5 ml, and high-speed stirring (about 2200 rpm) is performed at 90 ° C. for 48 seconds. Saturated aqueous ammonium chloride solution (2 ml) was added to this reaction solution, and treated with a conventional method, allyl acetoacetic acid butyl ester was obtained in a yield of 4%.
アセト酢酸ペンチルエステル（２．２ｍｏｌ／ｌ）、酢酸アリルエステル（２．０ｍｏｌ／ｌ）及びメシチレンの混合液（Ｏ6液）を調製する。同様にアリルパラジウムクロリドダイマー（０．００７５ｍｏｌ／ｌ）、ホスフィニジントリス（ベンゼンスルホン酸）トリナトリウム塩配位子（０．０６ｍｏｌ／ｌ）、炭酸カリウム（１．６５ｍｏｌ／ｌ）の水溶液（Ｗ液）を調製する。それぞれの溶液を流速０．２５ｍｌ／ｍｉｎで、９０℃の恒温槽に入った内容積４００μｌ、内径０．２５ｍｍのチューブ状マイクロリアクタに導入する。リアクタから出てきた溶液を飽和塩化アンモニウム水溶液中に滴下し反応を停止させる。反応液を定法に従って処理すると、アリルアセト酢酸ペンチルエステルが収率１４％で得られた。 A mixed liquid (O 6 liquid) of acetoacetic acid pentyl ester (2.2 mol / l), acetic acid allyl ester (2.0 mol / l) and mesitylene is prepared. Similarly, an allyl palladium chloride dimer (0.0075 mol / l), an phosphinidin tris (benzenesulfonic acid) trisodium salt ligand (0.06 mol / l), an aqueous solution of potassium carbonate (1.65 mol / l) (W Liquid). Each solution is introduced at a flow rate of 0.25 ml / min into a tubular microreactor having an internal volume of 400 μl and an inner diameter of 0.25 mm in a thermostat at 90 ° C. The solution coming out of the reactor is dropped into a saturated aqueous ammonium chloride solution to stop the reaction. When the reaction solution was treated according to a conventional method, allyl acetoacetic acid pentyl ester was obtained in a yield of 14%.
比較例１０
内容積５ｍｌの円錐状反応容器に実施例１９のＯ6液（０．２ｍｌ）とＷ液（０．２ｍｌ）を入れ、４８秒間９０℃で高速撹拌（約２２００ｒｐｍ）する。この反応液に飽和塩化アンモニウム水溶液（２ｍｌ）を加え、定法により処理するとアリルアセト酢酸ペンチルエステルが収率１％で得られた。
Comparative Example 10
The O 6 solution (0.2 ml) and the W solution (0.2 ml) of Example 19 are placed in a conical reaction vessel having an internal volume of 5 ml, and high-speed stirring (about 2200 rpm) is performed at 90 ° C. for 48 seconds. Saturated aqueous ammonium chloride solution (2 ml) was added to this reaction solution and treated by a conventional method to obtain allyl acetoacetic acid pentyl ester in a yield of 1%.
マロン酸ジエチルエステル（２．２ｍｏｌ／ｌ）、酢酸アリルエステル（２．０ｍｏｌ／ｌ）及びメシチレンの混合液（Ｏ7液）を調製する。同様にアリルパラジウムクロリドダイマー（０．００７５ｍｏｌ／ｌ）、ホスフィニジントリス（ベンゼンスルホン酸）トリナトリウム塩配位子（０．０６ｍｏｌ／ｌ）、炭酸カリウム（１．６５ｍｏｌ／ｌ）の水溶液（Ｗ液）を調製する。それぞれの溶液を流速０．２５ｍｌ／ｍｉｎで、９０℃の恒温槽に入った内容積４００μｌ、内径０．２５ｍｍのチューブ状マイクロリアクタに導入する。リアクタから出てきた溶液を飽和塩化アンモニウム水溶液中に滴下し反応を停止させる。反応液を定法に従って処理すると、アリルマロン酸ジエチルエステルが収率１０％で得られた。 A mixed liquid (O 7 liquid) of malonic acid diethyl ester (2.2 mol / l), acetic acid allyl ester (2.0 mol / l) and mesitylene is prepared. Similarly, an allyl palladium chloride dimer (0.0075 mol / l), an phosphinidin tris (benzenesulfonic acid) trisodium salt ligand (0.06 mol / l), an aqueous solution of potassium carbonate (1.65 mol / l) (W Liquid). Each solution is introduced at a flow rate of 0.25 ml / min into a tubular microreactor having an internal volume of 400 μl and an inner diameter of 0.25 mm in a thermostat at 90 ° C. The solution coming out of the reactor is dropped into a saturated aqueous ammonium chloride solution to stop the reaction. When the reaction solution was treated according to a conventional method, allylmalonic acid diethyl ester was obtained in a yield of 10%.
比較例１１
内容積５ｍｌの円錐状反応容器に実施例２０のＯ7液（０．２ｍｌ）とＷ液（０．２ｍｌ）を入れ、４８秒間９０℃で高速撹拌（約２２００ｒｐｍ）する。この反応液に飽和塩化アンモニウム水溶液（２ｍｌ）を加え、定法により処理するとアリルマロン酸ジエチルエステルが収率２％で得られた。
Comparative Example 11
The O 7 liquid (0.2 ml) and W liquid (0.2 ml) of Example 20 are placed in a conical reaction vessel having an internal volume of 5 ml, and stirred at 90 ° C. for 48 seconds at a high speed (about 2200 rpm). Saturated aqueous ammonium chloride solution (2 ml) was added to this reaction solution and treated by a conventional method, whereby allylmalonic acid diethyl ester was obtained in a yield of 2%.
アセチルブチロラクトン（３．３ｍｏｌ／ｌ）、酢酸アリルエステル（３．０ｍｏｌ／ｌ）及びメシチレンの混合液（Ｏ8液）を調製する。同様にアリルパラジウムクロリドダイマー（０．００７５ｍｏｌ／ｌ）、ホスフィニジントリス（ベンゼンスルホン酸）トリナトリウム塩配位子（０．０６ｍｏｌ／ｌ）、炭酸カリウム（１．６５ｍｏｌ／ｌ）の水溶液（Ｗ液）を調製する。それぞれの溶液を流速０．２５ｍｌ／ｍｉｎで、９０℃の恒温槽に入った内容積４００μｌ、内径０．２５ｍｍのチューブ状マイクロリアクタに導入する。リアクタから出てきた溶液を飽和塩化アンモニウム水溶液中に滴下し反応を停止させる。反応液を定法に従って処理すると、アリルアセチルブチロラクトンが収率９８％で得られた。 A mixed liquid (O 8 liquid) of acetylbutyrolactone (3.3 mol / l), acetic acid allyl ester (3.0 mol / l) and mesitylene is prepared. Similarly, an allyl palladium chloride dimer (0.0075 mol / l), an phosphinidin tris (benzenesulfonic acid) trisodium salt ligand (0.06 mol / l), an aqueous solution of potassium carbonate (1.65 mol / l) (W Liquid). Each solution is introduced at a flow rate of 0.25 ml / min into a tubular microreactor having an internal volume of 400 μl and an inner diameter of 0.25 mm in a thermostat at 90 ° C. The solution coming out of the reactor is dropped into a saturated aqueous ammonium chloride solution to stop the reaction. When the reaction solution was treated according to a conventional method, allylacetylbutyrolactone was obtained in a yield of 98%.
比較例１２
内容積５ｍｌの円錐状反応容器に実施例２１のＯ8液（０．２ｍｌ）とＷ液（０．２ｍｌ）を入れ、４８秒間９０℃で高速撹拌（約２２００ｒｐｍ）する。この反応液に飽和塩化アンモニウム水溶液（２ｍｌ）を加え、定法により処理するとアリルアセチルブチロラクトンが収率６５％で得られた。
Comparative Example 12
The O 8 solution (0.2 ml) and the W solution (0.2 ml) of Example 21 are placed in a conical reaction vessel having an internal volume of 5 ml and stirred at a high speed (about 2200 rpm) at 90 ° C. for 48 seconds. Saturated aqueous ammonium chloride solution (2 ml) was added to this reaction solution and treated by a conventional method to obtain allylacetylbutyrolactone in a yield of 65%.
医薬又はその合成中間体のようなファインケミカルズの製造に有用である。 It is useful for the production of fine chemicals such as pharmaceuticals or synthetic intermediates thereof.
Claims (2)
芳香族炭化水素類、脂肪族炭化水素類およびハロゲン系溶媒からなる群から選択される有機溶媒に含有される有機化合物原料とを接触させて均一系触媒反応をさせたのち、触媒含有水性媒体を有機相から分離し、触媒として再利用することを特徴とする有機化合物の製造方法であって、
前記有機化合物原料が、一般式
で表わされる化合物、及び一般式
で表わされる化合物の組合せであり、得られる有機化合物が、一般式
で表わされる化合物である有機化合物の製造方法。 In a tubular microreactor, an aqueous medium containing a catalyst comprising a transition metal complex selected from the group consisting of nickel complex, palladium complex, platinum complex, rhodium complex and iridium complex and a water-soluble ligand;
After contacting the organic compound raw material contained in an organic solvent selected from the group consisting of aromatic hydrocarbons, aliphatic hydrocarbons, and halogen-based solvents to cause a homogeneous catalytic reaction, a catalyst-containing aqueous medium is obtained. A method for producing an organic compound characterized in that it is separated from an organic phase and reused as a catalyst,
The organic compound raw material has the general formula
And a compound represented by the general formula
A combination of compounds represented by the formula:
The manufacturing method of the organic compound which is a compound represented by these.
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