KR100782583B1 - Coupling method for unsaturated hydrocarbon compounds, which employs organoindium compound as coupling agent - Google Patents
Coupling method for unsaturated hydrocarbon compounds, which employs organoindium compound as coupling agent Download PDFInfo
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- KR100782583B1 KR100782583B1 KR1020010044299A KR20010044299A KR100782583B1 KR 100782583 B1 KR100782583 B1 KR 100782583B1 KR 1020010044299 A KR1020010044299 A KR 1020010044299A KR 20010044299 A KR20010044299 A KR 20010044299A KR 100782583 B1 KR100782583 B1 KR 100782583B1
- Authority
- KR
- South Korea
- Prior art keywords
- group
- unsaturated hydrocarbon
- hydrogen
- indium
- compound
- Prior art date
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- 150000002430 hydrocarbons Chemical class 0.000 title claims abstract description 34
- 229930195735 unsaturated hydrocarbon Natural products 0.000 title claims abstract description 30
- 150000001875 compounds Chemical class 0.000 title claims abstract description 14
- 239000007822 coupling agent Substances 0.000 title abstract description 5
- 238000010168 coupling process Methods 0.000 title description 3
- 229910052738 indium Inorganic materials 0.000 claims abstract description 38
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 23
- 125000005843 halogen group Chemical group 0.000 claims abstract description 5
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 37
- -1 o- Tolyl Chemical group 0.000 claims description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 24
- 238000005859 coupling reaction Methods 0.000 claims description 18
- 239000003054 catalyst Substances 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 239000000460 chlorine Substances 0.000 claims description 13
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 238000011065 in-situ storage Methods 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 6
- 239000003446 ligand Substances 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 101150003085 Pdcl gene Proteins 0.000 claims description 4
- 150000001336 alkenes Chemical class 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 claims description 4
- 150000002736 metal compounds Chemical class 0.000 claims description 4
- 239000000654 additive Substances 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical group C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 125000005425 toluyl group Chemical group 0.000 claims description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
- 150000005621 tetraalkylammonium salts Chemical class 0.000 claims 1
- 229910052751 metal Inorganic materials 0.000 abstract description 18
- 239000002184 metal Substances 0.000 abstract description 18
- 150000002472 indium compounds Chemical class 0.000 abstract description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
- LNAMMBFJMYMQTO-FNEBRGMMSA-N chloroform;(1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].ClC(Cl)Cl.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 LNAMMBFJMYMQTO-FNEBRGMMSA-N 0.000 description 11
- 229910052763 palladium Inorganic materials 0.000 description 9
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- HFEHLDPGIKPNKL-UHFFFAOYSA-N allyl iodide Chemical compound ICC=C HFEHLDPGIKPNKL-UHFFFAOYSA-N 0.000 description 5
- 125000000524 functional group Chemical group 0.000 description 5
- RJFCFNWLPJRCLR-UHFFFAOYSA-N 1-prop-2-enylnaphthalene Chemical compound C1=CC=C2C(CC=C)=CC=CC2=C1 RJFCFNWLPJRCLR-UHFFFAOYSA-N 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 150000002902 organometallic compounds Chemical class 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 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 4
- NHPPIJMARIVBGU-UHFFFAOYSA-N 1-iodonaphthalene Chemical compound C1=CC=C2C(I)=CC=CC2=C1 NHPPIJMARIVBGU-UHFFFAOYSA-N 0.000 description 3
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- 150000001503 aryl iodides Chemical class 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 238000006619 Stille reaction Methods 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 2
- QSGNIZYSOOADSE-VMPITWQZSA-N [(1e)-penta-1,4-dienyl]benzene Chemical compound C=CC\C=C\C1=CC=CC=C1 QSGNIZYSOOADSE-VMPITWQZSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000001502 aryl halides Chemical class 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 125000006575 electron-withdrawing group Chemical group 0.000 description 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000006053 organic reaction Methods 0.000 description 2
- 125000002524 organometallic group Chemical group 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- JSCUZAYKVZXKQE-JXMROGBWSA-N (2e)-1-bromo-3,7-dimethylocta-2,6-diene Chemical compound CC(C)=CCC\C(C)=C\CBr JSCUZAYKVZXKQE-JXMROGBWSA-N 0.000 description 1
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
- SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 1
- AVMHMVJVHYGDOO-NSCUHMNNSA-N (e)-1-bromobut-2-ene Chemical compound C\C=C\CBr AVMHMVJVHYGDOO-NSCUHMNNSA-N 0.000 description 1
- JZJWCDQGIPQBAO-UHFFFAOYSA-N 1-(4-iodophenyl)ethanone Chemical compound CC(=O)C1=CC=C(I)C=C1 JZJWCDQGIPQBAO-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- KCBAMQOKOLXLOX-BSZYMOERSA-N CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O Chemical compound CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O KCBAMQOKOLXLOX-BSZYMOERSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- MVTQIFVKRXBCHS-SMMNFGSLSA-N N-[(3S,6S,12R,15S,16R,19S,22S)-3-benzyl-12-ethyl-4,16-dimethyl-2,5,11,14,18,21,24-heptaoxo-19-phenyl-17-oxa-1,4,10,13,20-pentazatricyclo[20.4.0.06,10]hexacosan-15-yl]-3-hydroxypyridine-2-carboxamide (10R,11R,12E,17E,19E,21S)-21-hydroxy-11,19-dimethyl-10-propan-2-yl-9,26-dioxa-3,15,28-triazatricyclo[23.2.1.03,7]octacosa-1(27),6,12,17,19,25(28)-hexaene-2,8,14,23-tetrone Chemical compound CC(C)[C@H]1OC(=O)C2=CCCN2C(=O)c2coc(CC(=O)C[C@H](O)\C=C(/C)\C=C\CNC(=O)\C=C\[C@H]1C)n2.CC[C@H]1NC(=O)[C@@H](NC(=O)c2ncccc2O)[C@@H](C)OC(=O)[C@@H](NC(=O)[C@@H]2CC(=O)CCN2C(=O)[C@H](Cc2ccccc2)N(C)C(=O)[C@@H]2CCCN2C1=O)c1ccccc1 MVTQIFVKRXBCHS-SMMNFGSLSA-N 0.000 description 1
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 1
- ZKTFUNZCYRUILZ-UHFFFAOYSA-N Papuamine Natural products C12C=CC=CC(C3CCCCC3C3)C3NCCCNC2CC2C1CCCC2 ZKTFUNZCYRUILZ-UHFFFAOYSA-N 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 1
- 108010080702 Virginiamycin Proteins 0.000 description 1
- 239000004188 Virginiamycin Substances 0.000 description 1
- YMOONIIMQBGTDU-VOTSOKGWSA-N [(e)-2-bromoethenyl]benzene Chemical compound Br\C=C\C1=CC=CC=C1 YMOONIIMQBGTDU-VOTSOKGWSA-N 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 150000001499 aryl bromides Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000007809 chemical reaction catalyst Substances 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 229940126086 compound 21 Drugs 0.000 description 1
- 229940126208 compound 22 Drugs 0.000 description 1
- 229940125833 compound 23 Drugs 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- QOUFDDUDXYJWHV-UHFFFAOYSA-N ethyl 2-iodobenzoate Chemical compound CCOC(=O)C1=CC=CC=C1I QOUFDDUDXYJWHV-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 150000002900 organolithium compounds Chemical class 0.000 description 1
- 150000002901 organomagnesium compounds Chemical class 0.000 description 1
- ZKTFUNZCYRUILZ-INNFTFPASA-N papuamine Chemical compound N([C@@H]1[C@@H]([C@H]2CCCC[C@@H]2C1)/C=C/C=C/[C@@H]12)CCCN[C@H]1C[C@@H]1[C@@H]2CCCC1 ZKTFUNZCYRUILZ-INNFTFPASA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 229920000098 polyolefin Polymers 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003606 tin compounds Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 229960003842 virginiamycin Drugs 0.000 description 1
- 235000019373 virginiamycin Nutrition 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 229910052726 zirconium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2/00—Preparation of hydrocarbons from hydrocarbons containing a smaller number of carbon atoms
- C07C2/02—Preparation of hydrocarbons from hydrocarbons containing a smaller number of carbon atoms by addition between unsaturated hydrocarbons
- C07C2/04—Preparation of hydrocarbons from hydrocarbons containing a smaller number of carbon atoms by addition between unsaturated hydrocarbons by oligomerisation of well-defined unsaturated hydrocarbons without ring formation
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/06—Halogens; Compounds thereof
- B01J27/08—Halides
- B01J27/10—Chlorides
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/06—Halogens; Compounds thereof
- B01J27/128—Halogens; Compounds thereof with iron group metals or platinum group metals
- B01J27/13—Platinum group metals
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0255—Phosphorus containing compounds
- B01J31/0267—Phosphines or phosphonium compounds, i.e. phosphorus bonded to at least one carbon atom, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, the other atoms bonded to phosphorus being either carbon or hydrogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C15/00—Cyclic hydrocarbons containing only six-membered aromatic rings as cyclic parts
- C07C15/40—Cyclic hydrocarbons containing only six-membered aromatic rings as cyclic parts substituted by unsaturated carbon radicals
- C07C15/56—Cyclic hydrocarbons containing only six-membered aromatic rings as cyclic parts substituted by unsaturated carbon radicals polycyclic condensed
- C07C15/58—Cyclic hydrocarbons containing only six-membered aromatic rings as cyclic parts substituted by unsaturated carbon radicals polycyclic condensed containing two rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C7/00—Purification; Separation; Use of additives
- C07C7/20—Use of additives, e.g. for stabilisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Analytical Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Water Supply & Treatment (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
본 발명은 유기 인듐 화합물을 결합체(coupling agent)로 사용하여 불포화 탄화수소 화합물들을 서로 결합시키는 방법에 관한 것이다. 보다 상세하게는, 본 발명은, 금속 인듐과 결합된 β,γ-불포화 탄화수소 화합물과 할로겐기 또는 트리플루오로메탄설폰일기로 치환된 불포화 탄화수소 화합물을 반응시켜, 상기 불포화 탄화수소 화합물들을 서로 결합시키는 방법에 대한 것이다.The present invention relates to a method of bonding unsaturated hydrocarbon compounds to each other using an organic indium compound as a coupling agent. More specifically, the present invention is a method of bonding the unsaturated hydrocarbon compounds to each other by reacting a β, γ-unsaturated hydrocarbon compound bonded with metal indium with an unsaturated hydrocarbon compound substituted with a halogen group or a trifluoromethanesulfonyl group. It is about.
β,γ-불포화유기인듐화합물(β,γ-unsaturated organoindium compound)β, γ-unsaturated organoindium compound
Description
본 발명은 유기 인듐 화합물을 결합체(coupling agent)로 사용하여 불포화 탄화수소 화합물들을 서로 결합시키는 방법에 관한 것이다. 보다 상세하게는, 본 발명은, 금속 인듐과 결합된 β,γ-불포화 탄화수소 화합물과 할로겐기 또는 트리플루오로메탄설폰일기로 치환된 불포화 탄화수소 화합물을 반응시켜, 상기 불포화 탄화수소 화합물들을 서로 결합시키는 방법에 대한 것이다.The present invention relates to a method of bonding unsaturated hydrocarbon compounds to each other using an organic indium compound as a coupling agent. More specifically, the present invention is a method of bonding the unsaturated hydrocarbon compounds to each other by reacting a β, γ-unsaturated hydrocarbon compound bonded with metal indium with an unsaturated hydrocarbon compound substituted with a halogen group or a trifluoromethanesulfonyl group. It is about.
일반적으로, 커플링 반응이라 함은 하기의 반응식과 같이 촉매존재하에서, 불포화 탄화수소 화합물들을 서로 결합시키는 화학반응을 의미한다. In general, the coupling reaction refers to a chemical reaction in which unsaturated hydrocarbon compounds are bonded to each other in the presence of a catalyst as in the following scheme.
불포화 탄화수소 화합물간의 탄소-탄소 결합을 형성시키는 방법은 금속 촉매 존재 하에 할로겐화 아릴 또는 할로겐화 비닐과 유기 금속 화합물간의 반응이 가장 일반적인 방법이다[(a) Heck, R. F. Palladium Reagents in Organic Synthesis; Academic Press: New York, 1985. (b) Trost, B. M.; Verhoeven, T. R. In Comprehensive Organometallic Chemistry; Wilkinson, G., Stone, F. G., Abel, E. W., Eds.; Pergamon: Oxford, 1982; Vol. 8, pp 799-938. (c) Farina, V. In Comprehensive Organometallic Chemistry II; Wilkinson, G., Stone, F. G., Abel, E. W., Eds.; Pergamon: Oxford, 1995; Vol. 12, pp 161-240. (d) Tsuji. J. Palladium Reagents and Catalyst; Wiley: Chichester, U.K., 1995: Chapter 4. (e) Diederich, F.; Stang, P. J., Eds. Metal-Catalyzed Cross-couplings Reactions; Wiley-VCH: Weinheim, 1998. (f) Malleron, J.; Fiaud, J.; Legros, J. Handbook of Palladium-Catalyzed Organic Reactions; Academic Press: San Diego, 1997.]. Carbon between the unsaturated hydrocarbon compound-method for forming a carbon bond is the reaction between an aryl halide or vinyl halide with an organometallic compound in the presence of metal catalyst is the most common methods [(a) Heck, R. F . Palladium Reagents in Organic Synthesis ; Academic Press: New York, 1985. (b) Trost, BM; Verhoeven, TR In Comprehensive Organometallic Chemistry ; Wilkinson, G., Stone, FG, Abel, EW, Eds .; Pergamon: Oxford, 1982; Vol. 8, pp 799-938. (c) Farina, V. In Comprehensive Organometallic Chemistry II ; Wilkinson, G., Stone, FG, Abel, EW, Eds .; Pergamon: Oxford, 1995; Vol. 12, pp 161-240. (d) Tsuji. J. Palladium Reagents and Catalyst ; Wiley: Chichester, UK, 1995: Chapter 4. (e) Diederich, F .; Stang, PJ, Eds. Metal-Catalyzed Cross-couplings Reactions ; Wiley-VCH: Weinheim, 1998. (f) Malleron, J .; Fiaud, J .; Legros, J. Handbook of Palladium-Catalyzed Organic Reactions ; Academic Press: San Diego, 1997.].
특히, 이들 중 팔라듐(Pd)과 니켈(Ni)을 금속 촉매로 사용하고, 유기 주석(Sn) 화합물을 커플링 시약(coupling agent)으로 사용하여 불포화 탄화수소 화합물간의 탄소-탄소 결합을 형성시키는 스틸레 커플링 반응[(a) Farina, V.; Krishnamurthy, V.; Scott, W. J. The Stille Reaction; Wiley: New York, 1998. (b) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. (c) Stille. J. K. Pure Appl. Chem. 1985, 57, 1771. (d) Mitchell. T. N. Synthesis 1992 , 803. (e) Farina. V.; Krishnamurthy. V.; Scott. W. J. Org. React. 1997, 50, 1. (f) Pereyre, M.; Quintard, J.; Rahm, A. Tin in Organic Synthesis; Butterworths: London 1987.]은 대표적인 커플링 반응으로 알려져 있다.Particularly, among these, stillets which form carbon-carbon bonds between unsaturated hydrocarbon compounds using palladium (Pd) and nickel (Ni) as metal catalysts and organic tin (Sn) compounds as coupling agents. Coupling reaction [(a) Farina, V .; Krishnamurthy, V .; Scott, W. J. The Stille Reaction ; Wiley: New York, 1998. (b) Stille, JK Angew. Chem., Int. Ed. Engl . 1986 , 25, 508. (c) Stille. JK Pure Appl. Chem . 1985 , 57 , 1771. (d) Mitchell. TN Synthesis 1992 , 803. (e) Farina. V .; Krishnamurthy. V .; Scott. WJ Org. React . 1997 , 50 , 1. (f) Pereyre, M .; Quintard, J .; Rahm, A. Tin in Organic Synthesis ; Butterworths: London 1987.] is known as a representative coupling reaction.
이러한 스틸레(Stille) 반응의 개발로 커플링 반응에 다양한 유기금속(B, Zn, Mg, Li, Cu, Al, Zr, Si)화합물의 사용이 가능하게 되었고[(a) Geissler. H. In Transition Metals for Organic Synthesis; Beller, M., Bolm. C., Eds.; Wiley-VCH: Weomheim, 1998; Chapter 2.10. (b) Negishi. E. In Organozinc Reagents; Knochel, P., Jones. P., Eds.; Oxford University Press; Oxford. U.K., 1999; Chapter 11. (c) Miyaura. N.; Suzuki. A. Chem. Rev. 1995, 95, 2457. (d) Yamamura, M.; Moritani,I,; Murahashi, S. J. Orgamomet. Chem. 1975, 91, C39-C42. (e) Tamao, K.; Kiso, Y.; Sumitani, K.; Kumada, M. J. Am. Chem. Soc. 1972, 94, 9268-9269. (f) Sekia, A.; Ishikawa, N. J. Organomet. Chem. 1976. 118, 349-354. (g) Hatanaka, Y.; Hiyama, T. Synlett 1991, 845-843, (h) Erdik, E. Tetrahedron 1992, 48, 9577-9648.], 특히, 스틸레 커플링 반응에 사용되는 유기 주석 화합물은 공기와 수분에 안정하고, 다양한 작용기들과 반응하지 않기 때문에 널리 사용되고 있다.The development of this Stille reaction enabled the use of various organometallic compounds (B, Zn, Mg, Li, Cu, Al, Zr, Si) in the coupling reaction [(a) Geissler. H. In Transition Metals for Organic Synthesis ; Beller, M., Bolm. C., Eds .; Wiley-VCH: Weomheim, 1998; Chapter 2.10. (b) Negishi. E. In Organozinc Reagents ; Knochel, P., Jones. P., Eds .; Oxford University Press; Oxford. UK, 1999; Chapter 11. (c) Miyaura. N .; Suzuki. A. Chem. Rev. 1995 , 95 , 2457. (d) Yamamura, M .; Moritani, I ,; Murahashi, S. J. Orgamomet. Chem . 1975 , 91, C39-C42. (e) Tamao, K .; Kiso, Y .; Sumitani, K .; Kumada, M. J. Am. Chem. Soc. 1972 , 94, 9268-9269. (f) Sekia, A .; Ishikawa, N. J. Organomet. Chem . 1976 . 118, 349-354. (g) Hatanaka, Y .; Hiyama, T. Synlett 1991 , 845-843, (h) Erdik, E. Tetrahedron 1992 , 48, 9577-9648.] In particular, organotin compounds used in stillet coupling reactions are stable to air and moisture, It is widely used because it does not react with various functional groups.
그러나, 상기의 스틸레 커플링 반응은 염화 트리알킬틴(trialkyltin chloride)과 알릴(allyl) 금속 음이온을 반응시켜 얻어지는 생성물에서 알릴 금속 음이온만을 정제하여 사용해야 하는데, 알릴 금속 음이온 이외에 분리하기가 어려운 부산물이 함께 생성되기 때문에 이에 대한 별도의 정제 과정이 필요하고, 또한, 상기 반응에서 얻어진 유기 주석 화합물이 독성을 가지고 있다는 문제점이 있다.However, the above-described styrene coupling reaction should be used only by purifying allyl metal anion from a product obtained by reacting trialkyltin chloride and allyl metal anion. Since it is produced together with a separate purification process for this, there is also a problem that the organic tin compound obtained in the reaction is toxic.
따라서, 이러한 문제점을 해결하기 위하여, 금속과 할로겐화 알릴을 반응시켜 얻은 생성물에서 알릴 금속 음이온을 분리하기 위한 별도의 정제과정을 거치지 않고 생성물 자체를 커플링 반응에 직접 사용하는 방법인 인 시튜(in situ) 방법이 사용되어 왔다. 예를 들어, 유기 마그네슘(organomagnesium)과 유기 리튬 (organolithium)화합물들은 금속과 할로겐화 알릴을 반응시켜 얻은 생성물에서 이들을 별도의 정제과정 없이 커플링 반응에 사용할 수 있기 때문에 커플링 시약(coupling agent)으로서 널리 사용되고 있다.Therefore, in order to solve this problem, in situ, which is a method of directly using the product itself in a coupling reaction without undergoing a separate purification process to separate allyl metal anions from a product obtained by reacting a metal with an allyl halide. Method has been used. For example, organomagnesium and organolithium compounds are widely used as coupling agents because they can be used in coupling reactions in products obtained by reacting metals with allyl halides. It is used.
그러나, 상기의 커플링 시약 역시 기질에 있는 다양한 작용기와의 반응성이 크기 때문에, 커플링 반응에 있어서 작용기 선택의 범위가 좁다는 단점을 가지고 있다.However, the coupling reagent also has a disadvantage in that the range of functional group selection in the coupling reaction is narrow because of its high reactivity with various functional groups in the substrate.
따라서, 생성물에서 유기 금속 화합물을 별도의 정제과정 없이도 커플링 반 응에 사용할 수 있는 동시에, 독성이 없으며, 작용기의 선택 범위가 높은 유기 금속 화합물을 사용하여 불포화 탄화수소 화합물간의 결합을 생성시키는 방법이 요구되고 있다.Therefore, there is a need for a method for producing an association between unsaturated hydrocarbon compounds by using an organometallic compound in the product, which can be used for coupling reaction without further purification, and at the same time, a non-toxic organometallic compound having a high selection of functional groups. It is becoming.
따라서, 본 발명에서는 상기의 유기 주석 화합물을 사용하는 스틸레 커플링 반응의 단점을 개선하고, 인듐 금속의 유기합성에 대한 이용성을 높이고자 금속 촉매 반응에 인듐 금속의 이용 가능성을 연구하여[(a) Li, C.-J. Tetrahedron 1996, 52, 5643. (b) Li, C.-J.; Chan, T.-H. Organic Reactions in Aqueous Media; Wiley: New York, 1997. (c) Li, C.-J. Chem. Rev. 1993, 93, 2023. Li, C.-J.; (d) Chan, T.-H. Tetrahedron 1999, 55, 11149. (e)Normera. R.; Miyazaki. S.-I.; Matsuda. H. J. Am. Chem. Soc. 1992, 114, 2378. (f) Perez. I. ; Sestelo, J.; Sarandeses, L. OrgLett 1999, 1, 1267. (g) Perez. I.; Sestelo, J.; Maestro. M. A.; Moourino. A.; Sarandeses, L.-A. J. Org. Chem. 1998, 63, 10074. (h) Cintas, P. Synlett 1995, 1087. (i) Babu, G.; Perumal, P. T. Aldrichimica Acta. 2000, 33, 16. (j) Chauhan, K. K.; Frost, C. G. J. Chem. Soc., Perkin Trans. 1, 2000, 3015. (k) Lee, P. H.; ang, K.; Lee, K.; Lee, C.-H.; Chang, S. Tetrahedron Lett. 2000, 41, 7521. (l) Lee, P. H.; Ahn, H.; Lee, K.; Sung, S.-Y.; Kim, S. Tetrahedron Lett. 2001, 42, 37.] 할로겐기로 치환된 β,γ-불포화 탄화수소 화합물을 인듐 금속과 반응시켜 얻은 인듐 금속이 결합된 β,γ-불포화 탄화수소 화합물을 불포화 탄화수소 화합물간 탄소-탄소 결합 방법을 개발하였다. Therefore, in the present invention, to improve the drawbacks of the stiletto coupling reaction using the above-described organotin compound and to improve the usability of the indium metal to the organic synthesis, the possibility of using the indium metal in the metal catalyst reaction [[a] ) Li, C.-J. Tetrahedron 1996 , 52 , 5643. (b) Li, C.-J .; Chan, T.-H. Organic Reactions in Aqueous Media ; Wiley: New York, 1997 . (c) Li, C.-J. Chem. Rev. 1993 , 93 , 2023. Li, C.-J .; (d) Chan, T.-H. Tetrahedron 1999 , 55 , 11149. (e) Norrmera. R .; Miyazaki. S.-I .; Matsuda. H. J. Am. Chem. Soc. 1992 , 114 , 2378. (f) Perez. I.; Sestelo, J .; Sarandeses, L. Org Lett 1999 , 1 , 1267. (g) Perez. I .; Sestelo, J .; Maestro. MA; Moourino. A .; Sarandeses, L.-AJ Org. Chem. 1998, 63, 10074. (h) Cintas, P. Synlett 1995 , 1087. (i) Babu, G .; Perumal, PT Aldrichimica Acta . 2000 , 33 , 16. (j) Chauhan, KK; Frost, CG J. Chem. Soc., Perkin Trans. 1 , 2000 , 3015. (k) Lee, PH; ang, K .; Lee, K .; Lee, C.-H .; Chang, S. Tetrahedron Lett . 2000 , 41 , 7521. (l) Lee, PH; Ahn, H .; Lee, K .; Sung, S.-Y .; Kim, S. Tetrahedron Lett . 2001 , 42 , 37.] A method of carbon-carbon bonding between unsaturated hydrocarbon compounds has been developed for indium metal-bonded β, γ-unsaturated hydrocarbon compounds obtained by reacting halogen-substituted β, γ-unsaturated hydrocarbon compounds with indium metal. .
따라서, 본 발명의 목적은 금속 인듐과 결합된 불포화 탄화수소 화합물을 결합체로 사용하여 불포화 탄화수소 화합물들간의 결합을 생성시키는 방법을 제공하는 것을 목적으로 한다. Accordingly, it is an object of the present invention to provide a method for producing bonds between unsaturated hydrocarbon compounds using an unsaturated hydrocarbon compound bonded with metal indium as a binder.
상기의 본 발명의 목적은 하기의 반응식 2에 나타낸 바와 같이, Y로 치환된 α,β-불포화 탄화수소 화합물(substituted-unsaturated hydrocarbon compound)과 인듐으로 치환된 β,γ-불포화 탄화수소 화합물(unsaturated organoindium compound)을 금속 화합물 촉매 존재하에서 반응시키는 불포화 탄화수소 화합물들간의 결합 방법을 제공함으로써 달성된다.The object of the present invention is as shown in Scheme 2 below, the Y substituted α, β-unsaturated hydrocarbon compound (substituted-unsaturated hydrocarbon compound) and indium substituted β, γ-unsaturated hydrocarbon compound (unsaturated organoindium compound) Is achieved by providing a process for bonding between unsaturated hydrocarbon compounds in the presence of a metal compound catalyst.
상기의 반응식에서,In the above scheme,
Y는 염소, 브롬, 요오드, OTf, OSO2F, IPhOTf 및 I(OH)OTs로 이루어진 군에서 선택되며, 이때 Tf는 트리플루오로메탄설폰일, Ph는 페닐, Ts는 파라-톨루엔설폰일을 나타내고;
R1 및 R3는 모두 수소이거나, 서로 결합하여 메타(meta) 또는 파라(para) 위치에 치환기를 갖는 시클로헥센기 또는 페닐기를 형성하며, 이때 메타 위치의 치환기는 수소 또는 -NO2이고, 파라 위치의 치환기는 수소, 부틸 및 아세틸로 이루어진 군에서 선택되고;
R2는 R1과 서로 결합하여 페닐기를 형성하거나, 수소, CO2Et 및 톨루일로 이루어진 군에서 선택되고;
R4 및 R5는 서로 독립적으로 수소, C1 내지 C6의 직쇄 또는 분지된 알킬 및 C1 내지 C6의 직쇄 또는 분지된 알켄으로 이루어진 군에서 선택되고; 및
R6은 수소 또는 메틸이거나, 또는 R4와 서로 결합하여 사이클로 헥센기를 형성한다.Y is selected from the group consisting of chlorine, bromine, iodine, OTf, OSO 2 F, IPhOTf and I (OH) OTs, where Tf is trifluoromethanesulfonyl, Ph is phenyl and Ts is para-toluenesulfonyl Represent;
R 1 and R 3 are both hydrogen or are bonded to each other to form a cyclohexene group or a phenyl group having a substituent at a meta or para position, wherein the substituent at the meta position is hydrogen or -NO 2 , and The substituent at the position is selected from the group consisting of hydrogen, butyl and acetyl;
R 2 is combined with R 1 to form a phenyl group, or is selected from the group consisting of hydrogen, CO 2 Et and toluyl;
R 4 and R 5 are each independently selected from the group consisting of hydrogen, C 1 to C 6 straight or branched alkyl and C 1 to C 6 straight or branched alkene; And
R 6 is hydrogen or methyl or combines with R 4 to form a cyclo hexene group.
본 발명에 있어서, 상기의 인듐과 결합된 불포화 탄화수소 화합물 (unsaturated organoindium compound)은, 하기의 반응식3에 나타낸 바와 같이, 금속 인듐과 할로겐기로 치환된 β,γ-불포화 탄화수소 화합물을 인 시튜(in situ)방법으로 반응시켜 제조되어지는 것을 특징으로 한다.In the present invention, the unsaturated hydrocarbon compound (unsaturated organoindium compound) in combination with the indium is in situ the β, γ- unsaturated hydrocarbon compound substituted with the metal indium and halogen as shown in Scheme 3, below, (in situ It is characterized in that it is produced by the reaction.
상기의 반응식에서, In the above scheme,
X는 염소, 브롬 또는 요오드로서, X가 염소일 경우에는 상기 반응이 요오드화 리튬 존재하에서 수행되는 것을 특징으로 하고,
R1 및 R2는 서로 독립적으로 수소, C1 내지 C6의 직쇄 또는 분지된 알킬 및 C1 내지 C6의 직쇄 또는 분지된 알켄으로 이루어진 군에서 선택되고; 및
R3은 수소 또는 메틸이거나, 또는 R1과 서로 결합하여 사이클로 헥센기를 형성한다.X is chlorine, bromine or iodine, when X is chlorine, the reaction is carried out in the presence of lithium iodide,
R 1 and R 2 are each independently selected from the group consisting of hydrogen, C 1 to C 6 straight or branched alkyl and C 1 to C 6 straight or branched alkene; And
R 3 is hydrogen or methyl, or combines with R 1 to form a cyclohexene group.
본 발명에 있어서, 인 시튜(in situ)방법이란 상기의 반응식3을 통해 생성된 생성물에서 불순물을 제거하여 정제된 인듐이 결합된 β,γ-불포화 탄화수소 화합물을 반응식2에 사용하는 것이 아니라, 상기의 반응식3의 결과 생성된 생성물 전부를 그대로 반응식2에 반응시키는 것을 의미한다.In the present invention, the in situ method does not use the purified indium-bonded β, γ-unsaturated hydrocarbon compound by removing impurities from the product generated through the above Scheme 3 in the above Scheme 2. This means that all of the resulting product of Scheme 3 is reacted as it is.
본 발명에 사용되는 촉매는 PdCl2, Pd(OAc)2, Pd(CH3CN)2Cl2, Pd(PPh3)4, 또는 Pd2dba3CHCl3에서 선택되는 것이 바람직하며, Pd2dba3CHCl3 또는 Pd(PPh3)4를 사용하는 것이 더욱 바람직하다. 이때 Ph는 페닐, dba는 디벤질리덴 아세톤을 나타낸다.The catalyst used in the present invention is preferably selected from PdCl 2 , Pd (OAc) 2 , Pd (CH 3 CN) 2 Cl 2 , Pd (PPh 3 ) 4 , or Pd 2 dba 3 CHCl 3 , and Pd 2 dba More preferably, 3 CHCl 3 or Pd (PPh 3 ) 4 is used. Ph is phenyl and dba is dibenzylidene acetone.
또한, 본 발명은 디메틸포름아미드(DMF) 또는 테트라히드로푸란(THF)의 용매하에서 수행되며, 리간드는 Ph3P, [2,6-(MeO)2Ph]3P, (o-Tolyl)3P, Ph3As, 또는 (2-Furyl)3P로 이루어진 포스핀 화합물을 사용할 수 있으며, Ph3P 또는 (2-Furyl)3P을 사용하는 것이 바람직하다. 이때, 이때 Ph는 페닐, Me는 메틸을 나타낸다.In addition, the present invention is carried out in a solvent of dimethylformamide (DMF) or tetrahydrofuran (THF), the ligand is Ph 3 P, [2,6- (MeO) 2 Ph] 3 P, ( o- Tolyl) 3 A phosphine compound consisting of P, Ph 3 As, or (2-Furyl) 3 P can be used, and it is preferable to use Ph 3 P or (2-Furyl) 3 P. In this case, Ph represents phenyl and Me represents methyl.
또한, 본 발명의 첨가제는 염화리튬(LiCl)을 사용하는 것이 바람직하다.In addition, the additive of the present invention preferably uses lithium chloride (LiCl).
이하, 실시예를 통하여 본 발명의 구성을 보다 구체적으로 설명하지만, 본 발명의 보통의 범위가 하기 실시예의 내용으로 한정되는 것은 아니다.Hereinafter, the structure of the present invention will be described in more detail with reference to Examples, but the general scope of the present invention is not limited to the following Examples.
실시예 1Example 1
각종 촉매 및 촉매 조성물을 사용했을 때의 수율 비교Yield comparison when using various catalysts and catalyst compositions
하기의 반응식 4와 같이 인듐 금속과 할로겐화 알릴(allyl halide) 화합물로부터 인 시튜(in situ) 방법으로 얻어지는 알릴 인듐(allyl indium, 1) 화합물을 다양한 조성의 팔라듐 촉매 존재하에서 1-요오드나프탈렌(1-iodonaphthalene)과 반응시켜 1-알릴나프탈렌(1-allylnaphthalene, 19)을 얻었다.As shown in Scheme 4, the allyl indium ( 1 ) compound obtained by the in situ method from the indium metal and the allyl halide compound is in the presence of a palladium catalyst having various compositions. 1-allylnaphthalene ( 19 ) was obtained by reacting with iodonaphthalene.
실험 결과, 표 1의 반응 6에 나타난 바와 같이 4%의 Pd(PPh3)4를 촉매로 사용한 경우에 알릴 인듐의 알릴기와 1-요오드나프탈렌의 1번 탄소가 결합된 1-알릴나프탈렌(19)를 91%의 수율로 얻었다.As a result, as shown in Reaction 6 of Table 1, when 4% of Pd (PPh 3 ) 4 was used as the catalyst, 1-allylnaphthalene ( 19 ) in which the allyl group of allyl indium and carbon number 1 of 1-iodine naphthalene were combined ( 19 ) Was obtained in a yield of 91%.
또한, 표 1의 반응 14에 나타난 바와 같이 2%의 Pd2dba3CHCl3를 촉매로 사용한 경우도 1-알릴나프탈렌(19)를 93%의 수율로 얻었다. In addition, as shown in Reaction 14 of Table 1, when 2% Pd 2 dba 3 CHCl 3 was used as a catalyst, 1-allyl naphthalene ( 19 ) was obtained in a yield of 93%.
표 1의 반응 1 내지 4 에 나타난 바와 같이 PdCl2, Pd(OAc)2, Pd(CH3CN) 2Cl2, Pd(PhCN)2Cl2를 촉매로 사용한 경우도 높은 수율로 1-알릴나프탈렌(19)을 생성하였다. As shown in Reactions 1 to 4 of Table 1, PdCl 2 , Pd (OAc) 2 , Pd (CH 3 CN) 2 Cl 2 , and Pd (PhCN) 2 Cl 2 were used as catalysts. ( 19 ) was produced.
리간드 중에는 표 1의 반응 14에 나타난 바와 같이 트리페닐포스핀 (triphenylphosphine)을 사용하였을 때 가장 좋은 수율로 1-알릴나프탈렌을 얻었다.Among the ligands, 1-allynaphthalene was obtained in the best yield when triphenylphosphine was used as shown in Reaction 14 of Table 1.
첨가제 중에는 표 1의 반응 11에 나타난 바와 같이 염화리튬(lithium chloride)이 존재하여야 반응이 진행하였다.Among the additives, lithium chloride (lithium chloride) must be present as shown in Reaction 11 of Table 1 to proceed with the reaction.
결론적으로, 촉매는 Pd(PPh3)4 또는 Pd2dba3CHCl3을 사용하고, 리간드는 트리페닐포스핀(triphenylphosphine)을 사용하였으며, 염화 리튬(lithium chloride)이 존재하고 용매로는 디메틸포름아미드(DMF)를 사용할 때 가장 좋은 수율로 생성물을 얻었다 (표 1의 반응 6, 14 참조).In conclusion, Pd (PPh 3 ) 4 or Pd 2 dba 3 CHCl 3 was used as the catalyst, triphenylphosphine was used as the ligand, lithium chloride was present, and dimethylformamide was used as the solvent. The product was obtained in the best yield when using (DMF) (see reactions 6 and 14 in Table 1).
또한 1.0 당량의 인듐과 1.5 당량의 요오드화 알릴로부터 생성된 알릴 인듐을 사용하였을 때 가장 높은 수율로 생성물을 얻었다.Also, the product was obtained in the highest yield when using 1.0 equivalent of indium and 1.5 equivalents of allyl iodide produced from allyl indium.
1.0 당량 이하의 인듐 또는 1.5 당량 이하의 요오드화 알릴(allyl iodide)을 사용한 경우 반응 시간이 길어지거나 수득률이 떨어졌다 (반응 12 내지 13 참조).When up to 1.0 equivalents of indium or up to 1.5 equivalents of allyl iodide were used, the reaction time was longer or the yield decreased (see Reactions 12-13).
상기의 결과들을 표 1에 나타내었다. The above results are shown in Table 1.
실시예 2Example 2
본 발명의 효율성을 알아보기 위하여 다양한 할로겐화 알릴을 인듐과 반응시켜 생성된 알릴 인듐을 할로겐기로 치환된 불포화 탄화수소 또는 플레이트기로 치환된 불포화 탄화수소와 반응시켰다. In order to understand the efficiency of the present invention, allyl indium produced by reacting various allyl halides with indium was reacted with unsaturated hydrocarbons substituted with halogen groups or unsaturated hydrocarbons substituted with plate groups.
표 2에 나타난 바와 같이 α나 β-위치에 다양한 치환체를 가지는 할로겐화 알릴의 경우 수득률과 반응 속도에서 큰 영향을 미치지 못하였고 높은 수율로 생성물을 얻었다. As shown in Table 2, in the case of allyl halide having various substituents in the α or β-position, the yield and the reaction rate did not have a significant effect, and the product was obtained in high yield.
가. 할로겐화 알릴에 치환된 치환체의 종류에 따른 수율 비교end. Yield Comparison According to the Types of Substituents Substituted in Allyl Halide
표 2의 반응 4에 나타난 바와 같이 최적 반응 조건하에서 1-요오드나프탈렌 (1-iodonaphthalene, 7)을 브롬화 알릴(allyl bromide)과 인듐(indium)으로부터 생성된 알릴 인듐과 반응시켜 1-알릴나프탈렌(1-allylnaphthalene, 19)을 87%의 수율로 얻었다.As shown in Reaction 4 of Table 2, under optimal reaction conditions, 1-iodonaphthalene ( 7 ) was reacted with allyl indium produced from allyl bromide and indium to yield 1-allylnaphthalene (1). -allylnaphthalene ( 19 ) was obtained in 87% yield.
표 2의 반응 5에 나타난 바와 같이 1-요오드나프탈렌 (1-iodonaphthalene, 7)을 크로틸 브로마이드(crotyl bromide; cis:trans=1:5)와 인듐과 반응시켜 생성된 생성물과 반응시켜 화합물 20(cis:trans=1.5:1)과 21을 얻었다. 이때 주생성물은 화합물 21이었다. As shown in Reaction 5 of Table 2, 1-iodonaphthalene ( 7 ) was reacted with crotyl bromide ( cis : trans = 1: 5) and indium to react with the resulting product to give Compound 20 ( cis : trans = 1.5: 1) and 21 were obtained. At this time, the main product was Compound 21 .
화합물 7과 프레닐 인듐(prenyl indium)을 반응시켜 화합물 22를 88%의 수율로 얻었다 (반응 6 참조). 화합물 7을 인듐과 브롬화 제라닐 (geranyl bromide)으로부터 생성된 제라닐 인듐(geranyl indium)과 반응시켜 수율 71%의 화합물 23(cis:trans=1:2)을 얻었다(반응 7 참조). Compound 7 was reacted with prenyl indium to obtain compound 22 in a yield of 88% (see Reaction 6). Compound 7 was reacted with geranyl indium produced from indium and geranyl bromide to yield 71% of compound 23 ( cis : trans = 1: 2) (see Reaction 7).
반응 8, 11, 18에 나타난 바와 같이 할로겐화 알릴로 3-브로모시클로헥센(3-bromocyclohexene)을 사용하여 반응을 시켰을 경우 원하는 화합물을 높은 수율로 얻었다.As shown in Reactions 8, 11 and 18, the desired compound was obtained in high yield when the reaction was carried out using halogenated allyl 3-bromocyclohexene.
나. 방향족 불포화 탄화수소에 치환된 치환체의 종류에 따른 수율 비교I. Yield Comparison According to the Substituents Substituted on Aromatic Unsaturated Hydrocarbons
반응 8 내지 19에 나타난 바와 같이 방향족(aromatic)고리에 다양한 치환체(n-butyl, acetyl, ketal, ethoxycarbonyl, nitro)가 존재하는 요오드화 아릴을 최적 조건하에 할로겐화 인듐과 반응시킨 결과 방향족 탄화수소에 치환된 치환체의 종류가 반응의 수율에 큰 영향을 미치지 못함을 알 수 있었다.As shown in Reactions 8 to 19, aryl iodide having various substituents ( n -butyl, acetyl, ketal, ethoxycarbonyl, and nitro) in the aromatic ring was reacted with indium halide under optimum conditions. It was found that the type of did not significantly affect the yield of the reaction.
반응 9 와 10에 나타난 바와 같이 치환체에 반응성이 큰 케톤기를 가지는 4-요오드아세토페논(4-iodoacetophenone)을 알릴 인듐과 반응시켰을 경우 알릴 인듐이 케톤은 공격하지 않고 요오드화 아릴과 반응하여 커플링 생성물만을 얻었다.As shown in Reactions 9 and 10, when 4-iodoacetophenone, which has a highly reactive ketone group, is reacted with allyl indium, allyl indium reacts with aryl iodide without attacking the ketone, but only the coupling product. Got it.
할로겐기로 치환된 불포화 탄화수소에 있어서 치환체의 위치에 대한 선택성을 알아보기 위하여 에틸 요오드벤조에이트(ethyl iodobenzoate)과 알릴 인듐을 반응시켰다. 그 결과 반응 12 내지 14에 나타난 바와 같이 에틸기(ethyl)기의 위치(ortho, meta, para)와 상관없이 높은 수율의 생성물을 얻었다. Ethyl iodobenzoate was reacted with allyl indium to determine the selectivity of the position of the substituent in the unsaturated hydrocarbon substituted with halogen. As a result, as shown in the reaction 12 to 14, a high yield of the product was obtained regardless of the position of the ethyl group ( ortho , meta , para ).
할로겐기로 치환된 불포화 탄화수소에 있어서 치환체에 전자를 끄는기 혹은 전자를 미는기(반응 8 참조)의 존재와 무관하게 최적조건에서 생성된 알릴 인듐(allyl indium)과 반응시켜 높은 수율로 알릴이 결합된 불포화 탄화수소를 얻었다. 특히 전자 끄는기를 가지는 할로겐화 아릴(aryl halide)의 경우 높은 수율로 탄소와 탄소간의 결합이 생성된 생성물을 얻었다. In unsaturated hydrocarbons substituted with halogen groups, allyl is bound in high yield by reaction with allyl indium produced under optimum conditions irrespective of the presence of electron withdrawing groups or electron pushing groups (see Reaction 8). An unsaturated hydrocarbon was obtained. In particular, in the case of aryl halides having an electron withdrawing group, a product in which carbon-to-carbon bonds were produced in high yield was obtained.
반응 1, 2에 나타난 바와 같이 불포화 탄화수소에 요오드로 치환되어 있는 요오드화 아릴(aryl iodide)이 브롬으로 치환되어 있는 브롬화 아릴(aryl bromide)보다 반응성이 더 좋았다. As shown in reactions 1 and 2, aryl iodide substituted with iodine in unsaturated hydrocarbons was more reactive than aryl bromide substituted with bromine.
반응 21에 나타난 바와 같이 β-브로모스틸렌(β-bromostyrene; cis:trans=1:4, 18)의 경우 알릴 인듐과 반응하여 1-페닐-1,4-펜타디엔(1-phenyl-1,4-pentadiene; cis:trans=1:4, 38)을 91%의 수율로 생성하였다.As shown in Reaction 21, in the case of β-bromostyrene ( cis : trans = 1: 4, 18 ), allyl indium reacted with 1-phenyl-1,4-pentadiene (1-phenyl-1, 4-pentadiene; cis : trans = 1: 4, 38 ) was produced in a yield of 91%.
반응 3, 20에 나타난 바와 같이 아릴 트리플루오로메탄설폰일(aryl trifluoromethanesulfonyl) 또는 비닐 트리플루오로메탄설폰일(vinyl trifluoromethanesulfonyl)를 알릴 인듐과 반응시킨 경우 화합물 19, 37이 각각 87%와 88%의 수율로 생성되었다.When aryl trifluoromethanesulfonyl or vinyl trifluoromethanesulfonyl was reacted with allyl indium as shown in Reactions 3 and 20, compounds 19 and 37 were 87% and 88%, respectively. Produced in yield.
상기의 결과들을 표 2와 3에 나타내었다.The results are shown in Tables 2 and 3.
a100℃, 디메틸포름아미드(DMF) 용매하에 16% 리간드와 3당량의 염화리튬(LiCl)의 존재하의 반응. 1당량의 인듐과 1.5당량의 요오드화 알릴의 반응으로부터 알릴 인듐을 얻었다. a reaction at 100 ° C. in the presence of 16% ligand and 3 equivalents of lithium chloride (LiCl) in dimethylformamide (DMF) solvent. Allyl indium was obtained from the reaction of 1 equivalent of indium and 1.5 equivalents of allyl iodide.
bTHF를 용매로 사용함. c염화리튬(LiCl)을 사용하지 않음. d인듐:요오드화 알릴=0.66:1 b Use THF as solvent. c Lithium chloride (LiCl) not used. d indium: allyl iodide = 0.66: 1
e인듐:요오드화알릴=1:1 e indium: allyl iodide = 1: 1
a부분입체이성질체의 비율 시스:트랜스=1.5:1. b 20(α):21(γ) 비율. c시스:트랜스 비율. d에틸벤조에이트. e부분입체이성질체의 비율 시스:트랜스=1.5:1. f 32(α):33(γ) 비율. g시스:트랜스=1:4 a ratio of diastereomers cis: trans = 1.5: 1. b 20 (α): 21 (γ) ratio. c Sheath: trans ratio. d ethylbenzoate. e ratio of diastereomers cis: trans = 1.5: 1. f 32 (α): 33 (γ) ratio. g sheath: trans = 1: 4
본 발명의 유기 인듐 금속을 사용한 불포화 탄화수소 화합물간의 탄소-탄소 결합 방법은 인 시튜(in situ) 방법으로 생성된 유기인듐화합물을 사용함으로써 불순물을 분리해내는 별도의 정제 과정이 불필요하다. The carbon-carbon bond method between unsaturated hydrocarbon compounds using the organic indium metal of the present invention does not require a separate purification process for separating impurities by using an organic indium compound produced by an in situ method.
또한, 상기 인듐 금속이 결합된 β,γ-불포화 탄화수소화합물은 반응성이 우수하고, 작용기 선택의 범위가 넓으며, 독성이 낮기 때문에 종래의 유기 주석 화합물을 사용했을 때의 단점인 부산물 제거의 어려움, 유기 주석 화합물의 독성의 단점을 극복하여 불포화 탄화수소 화합물간의 탄소-탄소 결합 생성물을 높은 수율로 얻을 수 있다.In addition, the β, γ-unsaturated hydrocarbon compound in which the indium metal is bonded has excellent reactivity, a wide range of functional group selection, and low toxicity. By overcoming the disadvantages of toxicity of organotin compounds, carbon-carbon bond products between unsaturated hydrocarbon compounds can be obtained in high yields.
현재 커플링 반응들이 천연물, 의약 및 농약 등의 합성에 많이 사용되고 있기 때문에, 본 발명의 유기 인듐 화합물을 사용한 커플링 반응은 폴리올레핀 매크롤리드(Polyolefin macrolide), 라파마이신(rapamycin), 버지아마이신 (virginiamycin), 스트리츠닌(strychnine), 파푸아민(papuamine), 헬리클로나디아민(heliclonadiamine), 고니오푸르푸론(goniofurfurone) 등의 합성에 이용될 수 있으며, 종래 커플링 반응의 여러 단점에 대한 보완으로 그 이용 가능성은 크다고 할 수 있다.Since the coupling reactions are widely used in the synthesis of natural products, medicines, and pesticides, the coupling reaction using the organic indium compound of the present invention is polyolefin macrolide, rapamycin, or virginiacin ( It can be used for the synthesis of virginiamycin, strychnine, papuamine, heliclonadiamine, goniofurfurone, etc. As such, its availability is large.
Claims (7)
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