JP2009242787A - Vitamin b12-modified core-shell type hyperbranched polymer and dehalogenation catalyst - Google Patents
Vitamin b12-modified core-shell type hyperbranched polymer and dehalogenation catalyst Download PDFInfo
- Publication number
- JP2009242787A JP2009242787A JP2009053934A JP2009053934A JP2009242787A JP 2009242787 A JP2009242787 A JP 2009242787A JP 2009053934 A JP2009053934 A JP 2009053934A JP 2009053934 A JP2009053934 A JP 2009053934A JP 2009242787 A JP2009242787 A JP 2009242787A
- Authority
- JP
- Japan
- Prior art keywords
- group
- vitamin
- formula
- hyperbranched polymer
- linear
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229920000587 hyperbranched polymer Polymers 0.000 title claims abstract description 136
- 239000011258 core-shell material Substances 0.000 title claims abstract description 60
- 238000005695 dehalogenation reaction Methods 0.000 title claims abstract description 18
- 239000003054 catalyst Substances 0.000 title abstract description 24
- 229940088594 vitamin Drugs 0.000 title 1
- 229930003231 vitamin Natural products 0.000 title 1
- 235000013343 vitamin Nutrition 0.000 title 1
- 239000011782 vitamin Substances 0.000 title 1
- 150000003722 vitamin derivatives Chemical class 0.000 title 1
- 229920000642 polymer Polymers 0.000 claims abstract description 46
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 229930003270 Vitamin B Natural products 0.000 claims abstract description 8
- 235000019156 vitamin B Nutrition 0.000 claims abstract description 8
- 239000011720 vitamin B Substances 0.000 claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims description 72
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 45
- 125000004432 carbon atom Chemical group C* 0.000 claims description 44
- FDJOLVPMNUYSCM-UVKKECPRSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2,7, Chemical compound [Co+3].N#[C-].C1([C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)[N-]\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O FDJOLVPMNUYSCM-UVKKECPRSA-L 0.000 claims description 41
- 239000000126 substance Substances 0.000 claims description 39
- -1 vitamin B 12 compound Chemical class 0.000 claims description 39
- 238000005227 gel permeation chromatography Methods 0.000 claims description 33
- 238000003786 synthesis reaction Methods 0.000 claims description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 239000004793 Polystyrene Substances 0.000 claims description 20
- 238000006116 polymerization reaction Methods 0.000 claims description 20
- 229920002223 polystyrene Polymers 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 125000002947 alkylene group Chemical group 0.000 claims description 15
- 125000004122 cyclic group Chemical group 0.000 claims description 13
- 239000007809 chemical reaction catalyst Substances 0.000 claims description 12
- 230000000977 initiatory effect Effects 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
- 230000001737 promoting effect Effects 0.000 claims description 9
- LMBWSYZSUOEYSN-UHFFFAOYSA-N diethyldithiocarbamic acid Chemical group CCN(CC)C(S)=S LMBWSYZSUOEYSN-UHFFFAOYSA-N 0.000 claims description 7
- 125000003700 epoxy group Chemical group 0.000 claims description 7
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 abstract description 6
- 238000000034 method Methods 0.000 abstract description 6
- 230000003100 immobilizing effect Effects 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 76
- 150000001867 cobalamins Chemical class 0.000 description 55
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 48
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 35
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
- 229910052757 nitrogen Inorganic materials 0.000 description 33
- 239000002904 solvent Substances 0.000 description 33
- DKVNPHBNOWQYFE-UHFFFAOYSA-N carbamodithioic acid Chemical group NC(S)=S DKVNPHBNOWQYFE-UHFFFAOYSA-N 0.000 description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 239000002002 slurry Substances 0.000 description 28
- 239000000047 product Substances 0.000 description 27
- 230000004048 modification Effects 0.000 description 26
- 238000012986 modification Methods 0.000 description 26
- 239000000843 powder Substances 0.000 description 24
- 238000003756 stirring Methods 0.000 description 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 17
- 229960001701 chloroform Drugs 0.000 description 17
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 16
- WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 16
- 239000000203 mixture Substances 0.000 description 16
- 238000006722 reduction reaction Methods 0.000 description 16
- 238000002371 ultraviolet--visible spectrum Methods 0.000 description 15
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 14
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- 239000012153 distilled water Substances 0.000 description 14
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 14
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 13
- 238000002484 cyclic voltammetry Methods 0.000 description 13
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 12
- 229910052753 mercury Inorganic materials 0.000 description 12
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 12
- 238000000862 absorption spectrum Methods 0.000 description 11
- 230000018044 dehydration Effects 0.000 description 11
- 238000006297 dehydration reaction Methods 0.000 description 11
- 239000006185 dispersion Substances 0.000 description 11
- 238000005259 measurement Methods 0.000 description 11
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- 238000007385 chemical modification Methods 0.000 description 10
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 9
- 239000004926 polymethyl methacrylate Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 230000005587 bubbling Effects 0.000 description 8
- AUZONCFQVSMFAP-UHFFFAOYSA-N disulfiram Chemical compound CCN(CC)C(=S)SSC(=S)N(CC)CC AUZONCFQVSMFAP-UHFFFAOYSA-N 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 8
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 8
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 8
- 229920000736 dendritic polymer Polymers 0.000 description 7
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 7
- 239000011941 photocatalyst Substances 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- SOGAXMICEFXMKE-UHFFFAOYSA-N Butylmethacrylate Chemical compound CCCCOC(=O)C(C)=C SOGAXMICEFXMKE-UHFFFAOYSA-N 0.000 description 6
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000010908 decantation Methods 0.000 description 6
- 239000000412 dendrimer Substances 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 6
- 229920001490 poly(butyl methacrylate) polymer Polymers 0.000 description 6
- 235000002597 Solanum melongena Nutrition 0.000 description 5
- 244000061458 Solanum melongena Species 0.000 description 5
- 229920006243 acrylic copolymer Polymers 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 238000011002 quantification Methods 0.000 description 5
- 238000001226 reprecipitation Methods 0.000 description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 4
- 238000007334 copolymerization reaction Methods 0.000 description 4
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 239000011259 mixed solution Substances 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 4
- 239000011345 viscous material Substances 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 3
- 229910021607 Silver chloride Inorganic materials 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000007256 debromination reaction Methods 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 0 C*(CC1CC1)CC(C(C)(C)CC(C)*C1)c2ccc1cc2 Chemical compound C*(CC1CC1)CC(C(C)(C)CC(C)*C1)c2ccc1cc2 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 208000034628 Celiac artery compression syndrome Diseases 0.000 description 2
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- AUALQMFGWLZREY-UHFFFAOYSA-N acetonitrile;methanol Chemical compound OC.CC#N AUALQMFGWLZREY-UHFFFAOYSA-N 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 229910017052 cobalt Inorganic materials 0.000 description 2
- 239000010941 cobalt Substances 0.000 description 2
- 229960002104 cyanocobalamin Drugs 0.000 description 2
- 235000000639 cyanocobalamin Nutrition 0.000 description 2
- 239000011666 cyanocobalamin Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 2
- 229910021397 glassy carbon Inorganic materials 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 238000000569 multi-angle light scattering Methods 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000001878 scanning electron micrograph Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- WWGXHTXOZKVJDN-UHFFFAOYSA-M sodium;n,n-diethylcarbamodithioate;trihydrate Chemical compound O.O.O.[Na+].CCN(CC)C([S-])=S WWGXHTXOZKVJDN-UHFFFAOYSA-M 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- SJMYWORNLPSJQO-UHFFFAOYSA-N tert-butyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OC(C)(C)C SJMYWORNLPSJQO-UHFFFAOYSA-N 0.000 description 2
- KBLZDCFTQSIIOH-UHFFFAOYSA-M tetrabutylazanium;perchlorate Chemical compound [O-]Cl(=O)(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC KBLZDCFTQSIIOH-UHFFFAOYSA-M 0.000 description 2
- 239000010409 thin film Substances 0.000 description 2
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
- GPOGMJLHWQHEGF-UHFFFAOYSA-N 2-chloroethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCCl GPOGMJLHWQHEGF-UHFFFAOYSA-N 0.000 description 1
- MNNZINNZIQVULG-UHFFFAOYSA-N 2-chloroethylbenzene Chemical compound ClCCC1=CC=CC=C1 MNNZINNZIQVULG-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- YEKPNMQQSPHKBP-UHFFFAOYSA-N 2-methyl-6-nitrobenzoic anhydride Chemical compound CC1=CC=CC([N+]([O-])=O)=C1C(=O)OC(=O)C1=C(C)C=CC=C1[N+]([O-])=O YEKPNMQQSPHKBP-UHFFFAOYSA-N 0.000 description 1
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
- IWTYTFSSTWXZFU-UHFFFAOYSA-N 3-chloroprop-1-enylbenzene Chemical compound ClCC=CC1=CC=CC=C1 IWTYTFSSTWXZFU-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- OSDWBNJEKMUWAV-UHFFFAOYSA-N Allyl chloride Chemical compound ClCC=C OSDWBNJEKMUWAV-UHFFFAOYSA-N 0.000 description 1
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- AHJKRLASYNVKDZ-UHFFFAOYSA-N DDD Chemical compound C=1C=C(Cl)C=CC=1C(C(Cl)Cl)C1=CC=C(Cl)C=C1 AHJKRLASYNVKDZ-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000002723 alicyclic group Chemical group 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
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- BBWBEZAMXFGUGK-UHFFFAOYSA-N bis(dodecylsulfanyl)-methylarsane Chemical compound CCCCCCCCCCCCS[As](C)SCCCCCCCCCCCC BBWBEZAMXFGUGK-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229950005228 bromoform Drugs 0.000 description 1
- IAQRGUVFOMOMEM-UHFFFAOYSA-N but-2-ene Chemical group CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical group C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 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 1
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000008151 electrolyte solution Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000009477 glass transition Effects 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000009878 intermolecular interaction Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 208000017983 photosensitivity disease Diseases 0.000 description 1
- 231100000434 photosensitization Toxicity 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- LLHKCFNBLRBOGN-UHFFFAOYSA-N propylene glycol methyl ether acetate Chemical compound COCC(C)OC(C)=O LLHKCFNBLRBOGN-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 238000002411 thermogravimetry Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Landscapes
- Catalysts (AREA)
- Graft Or Block Polymers (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Abstract
Description
本発明は、ビタミンＢ12修飾ハイパーブランチポリマー及び脱ハロゲン化触媒に関する。 The present invention relates to a vitamin B 12 modified hyperbranched polymer and a dehalogenation catalyst.
ハイパーブランチポリマーはデンドリマーと共にデンドリティック（樹枝状）ポリマーとして分類され、従来の高分子は一般的に紐状の形状であるのに対し、これらのデンドリティックポリマーは積極的に分枝を導入している点でその特異な構造を有し、特に末端基数の多さがデンドリティックポリマーの最も顕著な特徴である。このような末端基数の多いデンドリティックポリマーは、末端基の種類によって分子間相互作用が大きく左右されるので、ガラス転移温度や溶解性、薄膜形成性などが大きく変化し、一般の線状高分子にはない特徴を有する。
ハイパーブランチポリマーのデンドリマーに対する利点は、その合成の簡便さが挙げられ、特に工業的生産においては有利である。一般にデンドリマーが保護−脱保護を繰り返し合成されるのに対し、ハイパーブランチポリマーは１分子中に２種類の置換基を合計３個以上もつ、いわゆるＡＢX型モノマーの１段階重合により合成される。
ビタミンＢ12は、テトラピロール系の平面配位子であるコリン環内の４個の窒素原子にコバルトが配位した金属錯体であり、中心コバルトが＋１ないし＋３の酸化状態をとることができるので、この多様な電子状態が自在に変化することにより、多彩な反応の触媒として応用されている。
高分子表面へのビタミンＢ12の固定化は、修飾電極の耐久性向上を目指したものや（非特許文献１、非特許文献２、非特許文献３参照）、高分子薄膜上への固定化（非特許文献４参照）が報告されているが、高度分岐高分子上へ固定化した検討はなされていない。また、電極上にビタミンＢ12化合物を共有結合で担持した修飾電極を用いて、電解質溶液中で電解還元することが報告されているが（非特許文献５参照）、かかる方法では、電解質溶液に伝導性を与えるために、大量の電解質を用いる必要があった。また触媒となるビタミンＢ12化合物を回収・再利用するにはクロマトグラフィーによる分離操作が必要であり、多大な労力を必要とした。
Hyperbranched polymers are classified as dendritic (dendritic) polymers together with dendrimers, while conventional polymers are generally string-like, whereas these dendritic polymers actively introduce branching. In particular, it has its unique structure, and especially the large number of terminal groups is the most prominent feature of dendritic polymers. Such dendritic polymers with a large number of terminal groups greatly affect the intermolecular interaction depending on the type of terminal group, so the glass transition temperature, solubility, thin film formability, etc. vary greatly, and general linear polymers It has characteristics that are not present.
The advantages of hyperbranched polymers over dendrimers include their ease of synthesis and are particularly advantageous in industrial production. In general, dendrimers are synthesized by repeated protection and deprotection, whereas hyperbranched polymers are synthesized by one-step polymerization of so-called AB X type monomers having a total of 3 or more of two kinds of substituents in one molecule.
Vitamin B 12 is a metal complex in which cobalt is coordinated to four nitrogen atoms in the choline ring, which is a tetrapyrrole-based planar ligand, and the central cobalt can take an oxidation state of +1 to +3. These various electronic states can be freely changed, so that they are applied as catalysts for various reactions.
Immobilization of vitamin B 12 on the polymer surface is aimed at improving the durability of the modified electrode (see Non-Patent Document 1, Non-Patent Document 2, Non-Patent Document 3), or immobilization on a polymer thin film. (Refer to Non-Patent Document 4) has been reported, but no studies have been made on immobilization on highly branched polymers. In addition, it has been reported that electrolytic reduction is performed in an electrolyte solution using a modified electrode in which a vitamin B 12 compound is covalently supported on the electrode (see Non-Patent Document 5). In order to provide conductivity, a large amount of electrolyte had to be used. Further, in order to recover and reuse the vitamin B 12 compound serving as a catalyst, a separation operation by chromatography is required, which requires a great deal of labor.
本発明は、高度分岐高分子であるコア−シェル型ハイパーブランチポリマーにビタミンＢ12化合物を共有結合で固定化し、高い触媒効率と、これまでの単分子触媒とは異なる生成物選択性を有する新規ハイブリッド触媒の提供、及びビタミンＢ12化合物を高分子に固定化することで、ビタミンＢ12触媒を容易に回収・再利用できる方法を提供することを目的とする。 The present invention is a novel compound in which a vitamin B 12 compound is covalently immobilized on a core-shell hyperbranched polymer, which is a highly branched polymer, and has high catalytic efficiency and product selectivity that is different from conventional single molecule catalysts. It is an object of the present invention to provide a method for easily recovering and reusing a vitamin B 12 catalyst by providing a hybrid catalyst and immobilizing a vitamin B 12 compound on a polymer.
本発明者らは、上記目的を達成するために鋭意検討した結果、コア−シェル型ハイパーブランチポリマーにビタミンＢ12化合物を共有結合で固定化した触媒を合成した。本触媒は、脱ハロゲン化反応において、高い触媒活性を有するとともに、複数のビタミンＢ12部位を、コア−シェル型ハイパーブランチポリマーのコア又はシェル構造部分の近接した場所に固定化しているため、これまでの触媒と異なり還元時に炭素−炭素結合を促進する効果を見出し、本発明を完成した。 As a result of intensive studies to achieve the above object, the present inventors have synthesized a catalyst in which a vitamin B 12 compound is immobilized on a core-shell hyperbranched polymer by a covalent bond. This catalyst has high catalytic activity in the dehalogenation reaction, and a plurality of vitamin B 12 sites are immobilized in the vicinity of the core or shell structure portion of the core-shell hyperbranched polymer. The present invention was completed by finding the effect of promoting the carbon-carbon bond during the reduction, unlike the above catalysts.
即ち、本発明は、第１観点として、下記の式（１）で表される構造を有し、ゲル浸透ク
ロマトグラフィによるポリスチレン換算で測定される重量平均分子量が２、０００ないし２０，０００，０００の整数であるビタミンＢ12修飾コア−シェル型ハイパーブランチポリマー
Ｅは、下記の式（２）で表される繰り返し構造を表し、
Ａ1は下記の式（３）または式（４）
Ａ3はエーテル結合またはエステル結合を含んでいてもよい炭素原子数１ないし２０の直
鎖状、枝分かれ状または環状のアルキレン基を表し、
Ｘ1、Ｘ2、Ｘ3及びＸ4は、それぞれ独立して、水素原子、炭素原子数１ないし２０のアルキル基、または炭素原子数１から２０のアルコキシ基を表す。）で表される基を表し、
Ａ2はエーテル結合またはエステル結合を含んでいてもよい炭素原子数１ないし２０の直
鎖状、枝分かれ状または環状のアルキレン基を表し、
Ｒ1は水素原子またはメチル基を表し、
Ｒ2は水素原子、炭素原子数１ないし２０の直鎖状もしくは枝分かれ状のヒドロキシルア
ルキル基、炭素原子数３ないし２０の直鎖状もしくは枝分かれ状のエポキシ基を含むアルキル基、または式（５）
Ｒ3ないしＲ9のいずれか１つは、前記式（２）における酸素原子と共有結合する単結合を表し、前記Ａ2−Ｏ基と共有結合しないＲ3ないしＲ9はそれぞれ独立に水素原子または炭
素原子数１ないし２０のアルコキシ基を表し、
Ｙ1はシアノ基、ヒドロキシル基またはメチル基を表し、
Ｙ2はＣｏ原子に配位している水分子を表す。）で表されるビタミンＢ12化合物を表し（
ただし、Ｒ2のうち少なくとも１つ以上は前記式（５）で表されるビタミンＢ12化合物を
表す。）、
Ｚ1は、水素原子またはメチル基を表し、
ｎ及びｍは繰り返し単位の数であって、それぞれ独立して、２ないし１００，０００を表す。］、
第２観点として、前記Ａ1が式（６）または式（７）
第３観点として、前記Ａ2が、−（ＣＨ2）k−（式中、ｋは２ないし１０の整数を表す
。）で表される基を表す、第１観点に記載のビタミンＢ12修飾コア−シェル型ハイパーブランチポリマー、
第４観点として、前記ビタミンＢ12化合物が下記の式（８）
Ｒ3ないしＲ8はそれぞれ独立に水素原子または炭素原子数１ないし２０のアルコキシ基を表し、
Ｙ1はシアノ基、ヒドロキシル基またはメチル基を表し、
Ｙ2はＣｏ原子に配位している水分子を表す。）で表される化合物であることを特徴とす
る第１観点に記載のビタミンＢ12修飾コア−シェル型ハイパーブランチポリマー、
第５観点として、第１観点ないし第４観点のいずれか１つに記載のビタミンＢ12修飾コア−シェル型ハイパーブランチポリマーを含むラジカル型有機合成反応触媒、
第６観点として、脱ハロゲン化反応の促進に用いる第５観点に記載のラジカル型有機合成反応触媒、
第７観点として、炭素−炭素結合反応の促進に用いる第５観点に記載のラジカル型有機合成反応触媒、
第８観点として、下記の式（９）で表される構造を有し、ゲル浸透クロマトグラフィによるポリスチレン換算で測定される重量平均分子量が２、０００ないし２０，０００，０００の整数であるコア−シェル型ハイパーブランチポリマー
Ａ3はエーテル結合またはエステル結合を含んでいてもよい炭素原子数１ないし２０の直
鎖状、枝分かれ状または環状のアルキレン基を表し、
Ｇはそれぞれ独立して、水素原子、またはＮ，Ｎ−ジエチルジチオカルバメート基を表し
、
Ｅは、下記の式（１０）で表される基を表し
鎖状、枝分かれ状または環状のアルキレン基を表し、
Ｒ2は水素原子、炭素原子数１ないし２０の直鎖状もしくは枝分かれ状のヒドロキシルア
ルキル基、炭素原子数３ないし２０の直鎖状もしくは枝分かれ状のエポキシ基を含むアルキル基を表し、
Ｒ1は水素原子またはメチル基を表し、
ｎ及びｍは繰り返し単位の数であって、それぞれ独立に、２ないし１００，０００を表す。］、
第９観点として、第８観点に記載のコア−シェル型ハイパーブランチポリマーの少なくとも１つの水酸基と、ビタミンＢ12化合物のいずれか１つのカルボキシル基とを、縮合剤の存在下で反応させることを特徴とする第１観点に記載のビタミンＢ12修飾コア−シェル型ハイパーブランチポリマーの製造方法、
第１０観点として、下記の式（１１）で表される構造を重合開始部位として、下記の式（１２）で表される直鎖構造の繰り返し単位と下記の式（１３）で表される枝分かれ構造の繰り返し単位とからなる重合鎖部分を有し、そして該重合鎖部分の重合終了部位に化学式（１４）で表される直鎖状の繰り返し構造を結合してなり、かつ式（１２）で表される直鎖構造の繰り返し単位の総数が１ないし１００，０００の整数であり、式（１３）で表される枝分かれ構造の繰り返し単位の総数が２ないし１００，０００の整数であり、ゲル浸透クロマトグラフィによるポリスチレン換算で測定される重量平均分子量が２，０００ないし２０，０００，０００であるビタミンＢ12修飾コア−シェル型ハイパーブランチポリマー
Ａ1は第１観点に記載の式（３）または式（４）で表される基を表し、
Ａ2はエーテル結合またはエステル結合を含んでいてもよい炭素原子数１ないし２０の直
鎖状、枝分かれ状または環状のアルキレン基を表し、
Ｒ1は水素原子またはメチル基を表し、
Ｒ2は水素原子、炭素原子数１ないし２０の直鎖状もしくは枝分かれ状のヒドロキシルア
ルキル基、炭素原子数３ないし２０の直鎖状もしくは枝分かれ状のエポキシ基を含むアルキル基、または第１観点に記載の式（５）で表されるビタミンＢ12化合物を表し（ただし、Ｒ2のうち少なくとも１つ以上は前記式（５）で表されるビタミンＢ12化合物を表す。
）、
Ｚ1は、水素原子またはメチル基を表し、
Ｚ2は、水素原子または炭素原子数１ないし２０の直鎖状もしくは枝分かれ状のアルキル
基を表し、
Ｚ3は、水素原子またはメチル基を表し、
Ｇは、それぞれ独立して、水素原子またはＮ，Ｎ−ジエチルジチオカルバメート基を表し、
ｐは繰り返し単位の数であって、それぞれ独立して、２ないし１００，０００を表す。]
、
第１１観点として、前記Ａ1が第２観点に記載の式（６）または式（７）で表される基
を表す、第１０観点に記載のビタミンＢ12修飾コア−シェル型ハイパーブランチポリマー、
第１２観点として、前記Ａ2が、−（ＣＨ2）k−（式中、ｋは２ないし１０の整数を表
す。）で表される基を表す、第１０観点に記載のビタミンＢ12修飾コア−シェル型ハイパーブランチポリマー、
第１３観点として、前記ビタミンＢ12化合物が第４観点に記載の式（８）で表される化合物であることを特徴とする第１０観点に記載のビタミンＢ12修飾コア−シェル型ハイパーブランチポリマー、
第１４観点として、第１０観点ないし第１３観点のいずれか１つに記載のビタミンＢ12修飾コア−シェル型ハイパーブランチポリマーを含むラジカル型有機合成反応触媒、
第１５観点として、脱ハロゲン化反応の促進に用いる第１４観点に記載のラジカル型有機合成反応触媒、
第１６観点として、炭素−炭素結合反応の促進に用いる第１４観点にラジカル型有機合成反応触媒である。
That is, as a first aspect, the present invention has a structure represented by the following formula (1), and has a weight average molecular weight of 2,000 to 20,000,000 measured in terms of polystyrene by gel permeation chromatography. Vitamin B 12 modified core-shell hyperbranched polymer that is an integer
E represents a repeating structure represented by the following formula (2),
A 1 is the following formula (3) or formula (4)
A 3 represents a linear, branched or cyclic alkylene group having 1 to 20 carbon atoms which may contain an ether bond or an ester bond,
X 1 , X 2 , X 3 and X 4 each independently represent a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, or an alkoxy group having 1 to 20 carbon atoms. ) Represents a group represented by
A 2 represents a linear, branched or cyclic alkylene group having 1 to 20 carbon atoms which may contain an ether bond or an ester bond,
R 1 represents a hydrogen atom or a methyl group,
R 2 represents a hydrogen atom, a linear or branched hydroxylalkyl group having 1 to 20 carbon atoms, an alkyl group containing a linear or branched epoxy group having 3 to 20 carbon atoms, or the formula (5)
Any one of R 3 to R 9 represents a single bond covalently bonded to the oxygen atom in the formula (2), and R 3 to R 9 not covalently bonded to the A 2 —O group are each independently a hydrogen atom; Or an alkoxy group having 1 to 20 carbon atoms,
Y 1 represents a cyano group, a hydroxyl group or a methyl group,
Y 2 represents a water molecule coordinated to a Co atom. ) Represents a vitamin B 12 compound represented by (
However, at least one of R 2 represents a vitamin B 12 compound represented by the formula (5). ),
Z 1 represents a hydrogen atom or a methyl group,
n and m are the number of repeating units, and each independently represents 2 to 100,000. ],
As a second aspect, the A 1 is represented by the formula (6) or the formula (7).
As a third aspect, the vitamin B 12 modification according to the first aspect, wherein A 2 represents a group represented by — (CH 2 ) k — (wherein k represents an integer of 2 to 10). Core-shell hyperbranched polymer,
As a fourth aspect, the vitamin B 12 compound is represented by the following formula (8):
R 3 to R 8 each independently represents a hydrogen atom or an alkoxy group having 1 to 20 carbon atoms,
Y 1 represents a cyano group, a hydroxyl group or a methyl group,
Y 2 represents a water molecule coordinated to a Co atom. Vitamin B 12 modified core-shell hyperbranched polymer according to the first aspect, characterized in that it is a compound represented by
As a fifth aspect, a radical type organic synthesis reaction catalyst containing the vitamin B 12 modified core-shell hyperbranched polymer according to any one of the first aspect to the fourth aspect,
As a sixth aspect, the radical-type organic synthesis reaction catalyst according to the fifth aspect used for promoting the dehalogenation reaction,
As a seventh aspect, the radical-type organic synthesis reaction catalyst according to the fifth aspect used for promoting a carbon-carbon bond reaction,
As an eighth aspect, a core-shell having a structure represented by the following formula (9) and having a weight average molecular weight of 2,000 to 20,000,000 measured in terms of polystyrene by gel permeation chromatography Type hyperbranched polymer
A 3 represents a linear, branched or cyclic alkylene group having 1 to 20 carbon atoms which may contain an ether bond or an ester bond,
Each G independently represents a hydrogen atom or an N, N-diethyldithiocarbamate group;
E represents a group represented by the following formula (10).
R 2 represents a hydrogen atom, a linear or branched hydroxylalkyl group having 1 to 20 carbon atoms, an alkyl group containing a linear or branched epoxy group having 3 to 20 carbon atoms,
R 1 represents a hydrogen atom or a methyl group,
n and m are the number of repeating units, and each independently represents 2 to 100,000. ],
As a ninth aspect, at least one hydroxyl group of the core-shell hyperbranched polymer according to the eighth aspect is reacted with any one carboxyl group of the vitamin B 12 compound in the presence of a condensing agent. A method for producing a vitamin B 12- modified core-shell hyperbranched polymer according to the first aspect;
As a tenth aspect, with a structure represented by the following formula (11) as a polymerization initiation site, a repeating unit having a linear structure represented by the following formula (12) and a branch represented by the following formula (13) Having a polymer chain part composed of a repeating unit of the structure, and a linear repeating structure represented by the chemical formula (14) bonded to the polymerization end part of the polymer chain part, and in the formula (12) The total number of repeating units represented by the linear structure is an integer of 1 to 100,000, the total number of repeating units of the branched structure represented by the formula (13) is an integer of 2 to 100,000, and gel permeation vitamin B 12 modified core weight average molecular weight measured in terms of polystyrene by chromatography is 20,000,000 to 2,000 - shell hyperbranched polymer
A 1 represents a group represented by Formula (3) or Formula (4) described in the first aspect;
A 2 represents a linear, branched or cyclic alkylene group having 1 to 20 carbon atoms which may contain an ether bond or an ester bond,
R 1 represents a hydrogen atom or a methyl group,
R 2 represents a hydrogen atom, a linear or branched hydroxylalkyl group having 1 to 20 carbon atoms, an alkyl group containing a linear or branched epoxy group having 3 to 20 carbon atoms, or the first aspect. It represents a vitamin B 12 compound represented by the formula (5) described above (however, at least one of R 2 represents a vitamin B 12 compound represented by the formula (5)).
),
Z 1 represents a hydrogen atom or a methyl group,
Z 2 represents a hydrogen atom or a linear or branched alkyl group having 1 to 20 carbon atoms,
Z 3 represents a hydrogen atom or a methyl group,
Each G independently represents a hydrogen atom or an N, N-diethyldithiocarbamate group;
p is the number of repeating units, and each independently represents 2 to 100,000. ]
,
As an eleventh aspect, the vitamin B 12- modified core-shell hyperbranched polymer according to the tenth aspect, in which the A 1 represents a group represented by the formula (6) or the formula (7) according to the second aspect,
As a twelfth aspect, the vitamin B 12 modification according to the tenth aspect, wherein A 2 represents a group represented by — (CH 2 ) k — (wherein k represents an integer of 2 to 10). Core-shell hyperbranched polymer,
As a thirteenth aspect, the vitamin B 12 modified core according to the tenth aspect, wherein the vitamin B 12 compound is a compound represented by the formula (8) described in the fourth aspect - shell hyperbranched polymer ,
As a fourteenth aspect, a radical type organic synthesis reaction catalyst comprising the vitamin B 12 modified core-shell hyperbranched polymer according to any one of the tenth aspect to the thirteenth aspect,
As a fifteenth aspect, the radical type organic synthesis reaction catalyst according to the fourteenth aspect used for promoting a dehalogenation reaction,
As a sixteenth aspect, a radical type organic synthesis reaction catalyst is a fourteenth aspect used for promoting a carbon-carbon bond reaction.
本発明のビタミンＢ12修飾コア−シェル型ハイパーブランチポリマー触媒を用いれば、脱ハロゲン化反応を高収率で実施することが可能となるとともに、これまでの反応では主生成物とすることが難しかった炭素−炭素結合反応物を高収率で得ることが可能となる。また、ビタミンＢ12修飾コア−シェル型ハイパーブランチポリマー触媒は、ビタミンＢ12化合物が末端基数の多いハイパーブランチポリマーに固定されていることにより、多くの活性点を有するため有効な触媒として期待される。また、反応混合液からビタミンＢ12修飾コア−シェル型ハイパーブランチポリマー触媒を容易に分離でき、触媒の再利用が可能となる。また、サイクリックボルタンメトリー（ＣＶ）において、基質（臭化フェネチル）が存在する時のみ、触媒電流が流れる特徴を有しており、基質が存在する時のみ働く、省エネ型酵素モデルとなっている。 If the vitamin B 12 modified core-shell hyperbranched polymer catalyst of the present invention is used, the dehalogenation reaction can be carried out in a high yield, and it has been difficult to obtain the main product in the previous reactions. It is possible to obtain a high yield of carbon-carbon bond reactants. Further, the vitamin B 12 modified core-shell hyperbranched polymer catalyst is expected to be an effective catalyst because it has many active sites because the vitamin B 12 compound is fixed to the hyperbranched polymer having a large number of terminal groups. . Further, the vitamin B 12 modified core-shell hyperbranched polymer catalyst can be easily separated from the reaction mixture, and the catalyst can be reused. Further, in cyclic voltammetry (CV), it has a feature that a catalytic current flows only when a substrate (phenethyl bromide) is present, and is an energy-saving enzyme model that works only when a substrate is present.
以下、本発明について詳細に説明する。
本発明のビタミンＢ12修飾ハイパーブランチポリマーは、コア−シェル型ハイパーブランチポリマーの少なくとも１つの官能基にビタミンＢ12化合物を共有結合で固定化した構造を有し、ゲル浸透クロマトグラフィによるポリスチレン換算で測定される重量平均分子量が２，０００ないし２０，０００，０００であるビタミンＢ12修飾ハイパーブランチポリマーである。
ここで、共有結合で固定化した構造とは、例えば、コア−シェル型ハイパーブランチポリマーの水酸基とビタミンＢ12化合物のカルボキシル基が、エステル結合により結合した
構造である。
本発明に用いられるビタミンＢ12化合物とはビタミンＢ12骨格を有する化合物であり、例えば、ビタミンＢ12（シアノコバラミン）が挙げられる。
具体的な本発明のビタミンＢ12修飾コア−シェル型ハイパーブランチポリマーは、前記した式（１）で表される構造式を有するビタミンＢ12修飾コア−シェル型ハイパーブランチポリマーである。
また、本発明のビタミンＢ12修飾コア−シェル型ハイパーブランチポリマーは、前記式（１１）で表される構造を重合開始部位として、前記式（１２）で表される直鎖構造の繰り返し単位と前記式（１３）で表される枝分かれ構造の繰り返し単位とからなる重合鎖部分を有し、そして該重合鎖部分の重合終了部位に前記化学式（１４）で表される直鎖状の繰り返し構造を結合してなり、かつ式（１２）で表される直鎖構造の繰り返し単位の総数が１ないし１００，０００の整数であり、式（１３）で表される枝分かれ構造の繰り返し単位の総数が２ないし１００，０００の整数であり、ゲル浸透クロマトグラフィによるポリスチレン換算で測定される重量平均分子量が２，０００ないし２０，０００，０００であるビタミンＢ12修飾コア−シェル型ハイパーブランチポリマーである。
Hereinafter, the present invention will be described in detail.
The vitamin B 12 modified hyperbranched polymer of the present invention has a structure in which a vitamin B 12 compound is covalently fixed to at least one functional group of a core-shell hyperbranched polymer, and is measured in terms of polystyrene by gel permeation chromatography. Vitamin B 12 modified hyperbranched polymer having a weight average molecular weight of 2,000 to 20,000,000.
Here, the structure fixed by the covalent bond is, for example, a structure in which the hydroxyl group of the core-shell hyperbranched polymer and the carboxyl group of the vitamin B 12 compound are bonded by an ester bond.
The vitamin B 12 compound used in the present invention is a compound having a vitamin B 12 skeleton, and examples thereof include vitamin B 12 (cyanocobalamin).
Specific vitamin B 12 the modified core of the present invention - shell hyperbranched polymer, vitamin B 12 modified core has a structure represented by the equation (1) - a shell hyperbranched polymer.
Further, the vitamin B 12 modified core-shell hyperbranched polymer of the present invention comprises a repeating unit having a linear structure represented by the formula (12) with the structure represented by the formula (11) as a polymerization initiation site. Having a polymer chain portion composed of a repeating unit of a branched structure represented by the formula (13), and a linear repeating structure represented by the chemical formula (14) at a polymerization end portion of the polymer chain portion. The total number of repeating units of the linear structure represented by the formula (12) is an integer of 1 to 100,000, and the total number of repeating units of the branched structure represented by the formula (13) is 2 to an integer of 100,000, vitamin B 12 modified core weight average molecular weight measured in terms of polystyrene by gel permeation chromatography is 20,000,000 to 2,000 - sheet A Le hyperbranched polymer.
前記式（１）及び式（１４）中のＧは、それぞれ独立して、水素原子、またはＮ，Ｎ−ジエチルジチオカルバメート基を表す。
前記式（１）中のＥは、前記式（２）で表される繰り返し構造を表す。
前記式（１）、式（１１）及び式（１３）中のＡ1は、前記式（３）または前記式（４
）で表される構造を表す。
前記式（２）及び式（１２）におけるＡ2並びに前記式（３）及び前記式（４）におけ
るＡ3は、エーテル結合またはエステル結合を含んでいてもよい炭素原子数１ないし２０
の直鎖状、枝分かれ状または環状のアルキレン基を表す。
前記式（３）におけるＸ1、Ｘ2、Ｘ3及びＸ4は、それぞれ独立して、水素原子、炭素原子数１ないし２０のアルキル基、または炭素原子数１ないし２０のアルコキシ基を表す。
前記式（２）及び式（１４）中のＺ1は、水素原子またはメチル基を表す。
前記式（１４）中のＺ2は、水素原子または炭素原子数１ないし２０の直鎖状もしくは
枝分かれ状のアルキル基を表す。
前記式（１２）中のＺ3は、水素原子またはメチル基を表す。
前記式（１）、式（１１）及び式（１３）中のＲ1は、水素原子、またはメチル基を表
す。
前記式（２）及び式（１２）中のＲ2は、水素原子、炭素原子数１ないし２０の直鎖状
もしくは枝分かれ状のヒドロキシル基、炭素原子数３ないし２０の直鎖状もしくは枝分かれ状のエポキシ基を含むアルキル基、または前記式（５）で表されるビタミンＢ12化合物を表す（ただし、少なくとも１つ以上のビタミンＢ12化合物を含む）。
Ｒ2のヒドロキシアルキル基の具体例としては、ヒドロキシメチル基、２−ヒドロキシ
エチル基、３−ヒドロキシプロピル基、４−ヒドロキシブチル基などの直鎖状ヒドロキシアルキル基、２−ヒドロキシプロピル基、２−ヒドロキシブチル基、３−ヒドロキシブチル基、２−メチル−３−ヒドロキシプロピル基、３−メチル−２−ヒドロキシプロピル基などの枝分かれ状ヒドロキシルアルキル基が挙げられる。
前記式（５）で表されるビタミンＢ12化合物としては、例えば、前記式（８）で表されるビタミンＢ12関連化合物が挙げられる。
前記式（５）において、Ｒ3ないしＲ8におけるアルコキシ基としては、例えばメトキシ基、エトキシ基、プロポキシ基、ブトキシ基などの炭素原子数１ないし２０のアルコキシ基が挙げられ、好ましくはメトキシ基である。
前記Ａ2及びＡ3のアルキレン基の具体例としては、メチレン基、エチレン基、ノルマルプロピレン基、ノルマルブチレン基、ノルマルヘキシレン基等の直鎖状アルキレン基、イソプロピレン基、イソブチレン基、２−メチルプロピレン基等の分岐状アルキレン基が挙げられる。また環状アルキレン基としては、炭素原子数３ないし３０の単環式、多環式、
架橋環式の環状構造の脂環式脂肪族基が挙げられる。具体的には、炭素数４以上のモノシクロ、ビシクロ、トリシクロ、テトラシクロ、ペンタシクロ構造等を有する基を挙げることができる。
前記Ｘ1、Ｘ2、Ｘ3及びＸ4の炭素原子数１ないし２０のアルキル基としては、メチル基、エチル基、イソプロピル基、シクロヘキシル基、ノルマルペンチル基等が挙げられる。炭素原子数１ないし２０のアルコキシ基としては、メトキシ基、エトキシ基、イソプロポキシ基、シクロヘキシルオキシ基、ノルマルペンチルオキシ基等が挙げられる。特にＸ1
、Ｘ2、Ｘ3及びＸ4としては、水素原子又は炭素原子数１ないし２０のアルキル基が好ま
しい。
また、前記式（１）のＡ1としては、前記式（３）または前記式（４）で表される構造
であることが好ましい。前記式（７）中、ｌは２ないし１０の整数を表し、ｌとしては２または３が好ましい。
G in the formula (1) and the formula (14) each independently represents a hydrogen atom or an N, N-diethyldithiocarbamate group.
E in the formula (1) represents a repeating structure represented by the formula (2).
In Formula (1), Formula (11), and Formula (13), A 1 represents Formula (3) or Formula (4).
) Represents a structure represented by
Formula (2) and A 3 in the formula A 2 and the formula in (12) (3) and the formula (4) is having 1 to carbon atoms which may contain an ether bond or an ester bond 20
Represents a linear, branched or cyclic alkylene group.
X 1 , X 2 , X 3 and X 4 in the formula (3) each independently represent a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, or an alkoxy group having 1 to 20 carbon atoms.
Z 1 in the formulas (2) and (14) represents a hydrogen atom or a methyl group.
Z 2 in the formula (14) represents a hydrogen atom or a linear or branched alkyl group having 1 to 20 carbon atoms.
Z 3 in the formula (12) represents a hydrogen atom or a methyl group.
R 1 in the formula (1), formula (11) and formula (13) represents a hydrogen atom or a methyl group.
R 2 in the formulas (2) and (12) is a hydrogen atom, a linear or branched hydroxyl group having 1 to 20 carbon atoms, a linear or branched group having 3 to 20 carbon atoms. It represents an alkyl group containing an epoxy group or a vitamin B 12 compound represented by the above formula (5) (however, it contains at least one vitamin B 12 compound).
Specific examples of the hydroxyalkyl group represented by R 2 include linear hydroxyalkyl groups such as hydroxymethyl group, 2-hydroxyethyl group, 3-hydroxypropyl group, 4-hydroxybutyl group, 2-hydroxypropyl group, 2- Examples thereof include branched hydroxylalkyl groups such as hydroxybutyl group, 3-hydroxybutyl group, 2-methyl-3-hydroxypropyl group and 3-methyl-2-hydroxypropyl group.
Examples of the vitamin B 12 compound represented by the formula (5) include vitamin B 12 related compounds represented by the formula (8).
In the formula (5), examples of the alkoxy group in R 3 to R 8 include an alkoxy group having 1 to 20 carbon atoms such as a methoxy group, an ethoxy group, a propoxy group, and a butoxy group. is there.
Specific examples of the alkylene group of A 2 and A 3 include linear alkylene groups such as methylene group, ethylene group, normal propylene group, normal butylene group, and normal hexylene group, isopropylene group, isobutylene group, 2- Examples thereof include branched alkylene groups such as a methylpropylene group. Examples of the cyclic alkylene group include monocyclic, polycyclic, 3 to 30 carbon atoms,
Examples thereof include alicyclic aliphatic groups having a crosslinked cyclic structure. Specific examples include groups having a monocyclo, bicyclo, tricyclo, tetracyclo, or pentacyclo structure having 4 or more carbon atoms.
Examples of the alkyl group having 1 to 20 carbon atoms of X 1 , X 2 , X 3 and X 4 include a methyl group, an ethyl group, an isopropyl group, a cyclohexyl group, and a normal pentyl group. Examples of the alkoxy group having 1 to 20 carbon atoms include methoxy group, ethoxy group, isopropoxy group, cyclohexyloxy group, and normal pentyloxy group. Especially X 1
X 2 , X 3 and X 4 are preferably a hydrogen atom or an alkyl group having 1 to 20 carbon atoms.
Further, A 1 in the formula (1) preferably has a structure represented by the formula (3) or the formula (4). In the formula (7), l represents an integer of 2 to 10, and l is preferably 2 or 3.
本発明のビタミンＢ12修飾コア−シェル型ハイパーブランチポリマーの製法としては、例えば、コア−シェル型ハイパーブランチポリマーの少なくとも１つの水酸基と、ビタミンＢ12化合物のいずれか１つのカルボキシル基とを、縮合剤の存在下で反応させる製法が挙げられる。本反応は、不活性溶媒中、塩基を添加して行うことが好ましい。
原料となる官能基として水酸基を有するコア−シェル型ハイパーブランチポリマーは、例えば、Ｊ．Ａｐｐｌ．Ｐｏｌｙ．Ｓｃｉ．，２００６，１００，３３４０−３３４５に記載の方法で、シェル部をＭＭＡの代わりにＨＥＭＡで構築した化合物が挙げられる。
縮合剤としては、Ｎ，Ｎ‘−ジシクロヘキシルカルボジイミド（ＤＣＣ）、１−エチル−３−（ジメチルアミノプロピル）カルボジイミド塩酸塩（ＥＤＣ・ＨＣｌ）、クロロギ酸エステルやトシル酸クロライドのような酸クロライド（混合酸無水物法）、または２−メチル−６−ニトロ安息香酸無水物のような酸無水物等が挙げられる。
塩基としては、例えば、三級アミンが使用され、具体的には、ピリジン、４−ジメチチルアミノピリジン（ＤＭＡＰ）、またはトリエチルアミン等が挙げられる。
不活性溶媒としては、塩化メチレン、クロロホルム等のハロゲン化炭化水素、テトラヒドロフラン、２−メチルテトラヒドロフラン、テトラヒドロピラン等の環状エーテル及びアセトニトリル等のニトリル系溶媒等並びにこれらの溶媒の混合溶液が挙げられる。
反応温度は、溶媒の氷点から沸点の範囲であれば特に制限されないが、操作上０℃ないし８０℃が好ましい。反応時間は、反応の速度に依存するが、数時間から数十日が好ましい。
Examples of the method for producing the vitamin B 12 modified core-shell hyperbranched polymer of the present invention include condensing at least one hydroxyl group of the core-shell hyperbranched polymer with any one carboxyl group of the vitamin B 12 compound. The manufacturing method made to react in presence of an agent is mentioned. This reaction is preferably performed by adding a base in an inert solvent.
The core-shell hyperbranched polymer having a hydroxyl group as a functional group as a raw material is disclosed in, for example, J.A. Appl. Poly. Sci. , 2006, 100, 3340-3345, and a compound in which the shell part is constructed with HEMA instead of MMA.
Condensation agents include N, N′-dicyclohexylcarbodiimide (DCC), 1-ethyl-3- (dimethylaminopropyl) carbodiimide hydrochloride (EDC · HCl), acid chlorides such as chloroformate and tosylic acid chloride (mixed) Acid anhydride method), or acid anhydrides such as 2-methyl-6-nitrobenzoic acid anhydride.
As the base, for example, a tertiary amine is used, and specific examples include pyridine, 4-dimethylmethyaminopyridine (DMAP), triethylamine, and the like.
Examples of the inert solvent include halogenated hydrocarbons such as methylene chloride and chloroform, cyclic ethers such as tetrahydrofuran, 2-methyltetrahydrofuran and tetrahydropyran, nitrile solvents such as acetonitrile, and a mixed solution of these solvents.
The reaction temperature is not particularly limited as long as it is in the range from the freezing point to the boiling point of the solvent. The reaction time depends on the reaction rate, but is preferably several hours to several tens of days.
本発明のビタミンＢ12修飾コア−シェル型ハイパーブランチポリマーは、ラジカル型有機合成反応の触媒として使用することができ、例えば、脱ハロゲン化反応、炭素−炭素結合反応等に好適に使用できる。
本発明のビタミンＢ12修飾コア−シェル型ハイパーブランチポリマー触媒を用いた脱ハロゲン化反応は、有機ハロゲン化物を有機溶媒中でビタミンＢ12修飾コア−シェル型ハイパーブランチポリマー触媒と酸化チタンのような固体光触媒の共存下、光照射することにより行うことができる。
固体光触媒としては、光を照射することにより触媒活性を示す固体であるが、紫外光照射ではハイブリッド触媒の分解の恐れがあり、可視光を照射することにより触媒活性を示す可視光応答型の光触媒が好ましく用いられる。可視光応答型光触媒としては、酸化チタンが挙げられ、通常、結晶性のもの、例えばアナターゼ型、ルチル型、アナターゼ・ルチル型、ブルッカイト型が用いられる。
照射する光は、固体光触媒として紫外光応答型の光触媒を用いた場合は紫外光が、可視光応答型の光触媒を用いた場合は可視光がそれぞれ用いられる。
本発明の脱ハロゲン化反応に用いうる溶媒としては、基質及びビタミンＢ12錯体に対して反応しないもの、例えばメタノール、エタノール、プロパノールなどのアルコール類、アセトンなどのケトン類、ベンゼン、トルエンなどの芳香族炭化水素類、アセトニトリル
、ベンゾニトリルなどが挙げられる。酸化チタンが光増感作用を効率良く起こすためには、価電子帯のホールと高い反応性を示す、アルコール類を含む溶媒系が望ましい。
本発明の脱ハロゲン化方法に適用される有機ハロゲン化物は、フッ素原子、塩素原子、臭素原子、ヨウ素原子などのハロゲン原子を有する有機化合物であって、例えば１，１−ビス（４−クロロフェニル）−２，２，２−トリクロロエタン〔ＤＤＴ〕、１，１−ビス（４−クロロフェニル）−２，２−ジクロロエタン〔ＤＤＤ〕、２−ブロモエチルベンゼン、２−クロロエチルベンゼン、臭化ベンジル、塩化ベンジルなどのハロゲン化芳香族炭化水素、クロロホルム、塩化メチレン、四塩化炭素、フルオロトリクロロメタン、１，１，１−トリクロロメタン、ブロモホルム、１−ブロモプロパン、２−ブロモプロパン、臭化アリル、塩化アリル、ヨウ化メチルなどのハロゲン化炭化水素などが挙げられる。
脱ハロゲン化温度は、通常２０℃ないし４０℃、好ましくは３０℃ないし３５℃程度である。脱ハロゲン化に要する時間は、通常６時間ないし２４時間程度である。
ビタミンＢ12化合物において、中心金属原子であるコバルト原子は通常、３価または２価であるが、−１ないし−２．０Ｖ ｖｓ． Ａｇ／ＡｇＣｌの電位をかけると１価に還元される。コバルト原子が１価に還元されたビタミンＢ12化合物は、高い還元力を示すので、本発明の脱ハロゲン化方法では、かかるビタミンＢ12化合物が、有機ハロゲン化物に作用して還元し、脱ハロゲン化するものと考えられる。
脱ハロゲン化後のビタミンＢ12化合物は、反応混合物から脱ハロゲン化物を回収した後、再利用することができる。脱ハロゲン化物を回収せずに、そのまま再利用することも可能である。
Vitamin B 12 the modified core of the present invention - shell hyperbranched polymer can be used as a catalyst for the radical-type organic synthesis reaction, for example, dehalogenation reaction, carbon - can be suitably used in the carbon bond reaction, and the like.
In the dehalogenation reaction using the vitamin B 12 modified core-shell hyperbranched polymer catalyst of the present invention, an organic halide is used in an organic solvent such as vitamin B 12 modified core-shell hyperbranched polymer catalyst and titanium oxide. It can be carried out by light irradiation in the presence of a solid photocatalyst.
The solid photocatalyst is a solid that exhibits catalytic activity when irradiated with light, but there is a risk of decomposition of the hybrid catalyst when irradiated with ultraviolet light, and a visible light responsive photocatalyst that exhibits catalytic activity when irradiated with visible light. Is preferably used. Examples of the visible light responsive photocatalyst include titanium oxide. Usually, crystalline ones such as anatase type, rutile type, anatase / rutile type and brookite type are used.
As the light to be irradiated, ultraviolet light is used when an ultraviolet light responsive photocatalyst is used as the solid photocatalyst, and visible light is used when a visible light responsive photocatalyst is used.
Solvents that can be used in the dehalogenation reaction of the present invention include those that do not react with the substrate and vitamin B 12 complex, for example, alcohols such as methanol, ethanol, and propanol, ketones such as acetone, and fragrances such as benzene and toluene. Group hydrocarbons, acetonitrile, benzonitrile and the like. In order for titanium oxide to efficiently cause photosensitization, a solvent system containing alcohols that exhibits high reactivity with holes in the valence band is desirable.
The organic halide applied to the dehalogenation method of the present invention is an organic compound having a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom, such as 1,1-bis (4-chlorophenyl). -2,2,2-trichloroethane [DDT], 1,1-bis (4-chlorophenyl) -2,2-dichloroethane [DDD], 2-bromoethylbenzene, 2-chloroethylbenzene, benzyl bromide, benzyl chloride, etc. Halogenated aromatic hydrocarbons, chloroform, methylene chloride, carbon tetrachloride, fluorotrichloromethane, 1,1,1-trichloromethane, bromoform, 1-bromopropane, 2-bromopropane, allyl bromide, allyl chloride, iodide And halogenated hydrocarbons such as methyl.
The dehalogenation temperature is usually about 20 ° C to 40 ° C, preferably about 30 ° C to 35 ° C. The time required for dehalogenation is usually about 6 to 24 hours.
In the vitamin B 12 compound, the cobalt atom as the central metal atom is usually trivalent or divalent, but −1 to −2.0 V vs. When a potential of Ag / AgCl is applied, it is reduced to monovalent. Since the vitamin B 12 compound in which the cobalt atom is reduced to a monovalent value exhibits a high reducing power, in the dehalogenation method of the present invention, the vitamin B 12 compound acts on the organic halide to reduce it, and dehalogenates. It is thought that
The vitamin B 12 compound after dehalogenation can be reused after recovering the dehalogenation product from the reaction mixture. The dehalogenated product can be reused as it is without being recovered.
以下、本発明について実施例を挙げて詳述するが、本発明はこれらの実施例に何ら限定されるものではない。ＵＶ−ｖｉｓスペクトル、ＩＲスペクトル、ＭＡＬＤＩ−ＴＯＦ−ＭＳ、ＧＰＣ、ＧＣ−ＭＳ、ＮＭＲ、サイクリックボルタンメトリー、ＳＥＭは次の装置により測定した。
ＵＶ−ｖｉｓスペクトル：Ｕ−３０００型紫外可視分光光度計（（株）日立ハイテクノロジーズ製）
ＩＲスペクトル：ＦＴ−ＩＲ４６０ｐｌｕｓ（日本分光（株）製）
ＭＡＬＤＩ−ＴＯＦ−ＭＳ：Ａｕｔｏｆｌｅｘ（（株）ブルカー製）
分取用ＧＰＣ：ＬＣ−９２０１Ｒ（日本分析工業（株）製）
分析用ＧＰＣ：Ｌ−２０００（（株）日立ハイテクノロジーズ社製）
ＧＣ−ＭＳ：ＧＣ−ＭＳ−ＱＰ５０５０ＡＨガスクロマトグラフ質量分析計（（株）島津製作所製）
ＮＭＲ：Ｂｒｕｋｅｒ ＡＶＡＮＣＥ−５００−Ｓ 超伝導核磁気共鳴装置（（株）ブルカー製）
光照射装置：ブラックライト（フナコシ（株）製、１５Ｗ）
サイクリックボルタンメトリー（ＣＶ）：ＣＶ ＢＡＳ ＡＬＳ−６３０Ｃ（（株）ＢＡＳ社製）
走査型電子顕微鏡（ＳＥＭ）：ＪＳＭ６７０１Ｆ（（株）島津製作所製）
Hereinafter, although an example is given and the present invention is explained in full detail, the present invention is not limited to these examples at all. UV-vis spectrum, IR spectrum, MALDI-TOF-MS, GPC, GC-MS, NMR, cyclic voltammetry, and SEM were measured by the following apparatus.
UV-vis spectrum: U-3000 type UV-visible spectrophotometer (manufactured by Hitachi High-Technologies Corporation)
IR spectrum: FT-IR460plus (manufactured by JASCO Corporation)
MALDI-TOF-MS: Autoflex (manufactured by Bruker)
Preparative GPC: LC-9201R (manufactured by Nippon Analytical Industries, Ltd.)
GPC for analysis: L-2000 (manufactured by Hitachi High-Technologies Corporation)
GC-MS: GC-MS-QP5050AH gas chromatograph mass spectrometer (manufactured by Shimadzu Corporation)
NMR: Bruker AVANCE-500-S superconducting nuclear magnetic resonance apparatus (manufactured by Bruker)
Light irradiation device: Black light (Funakoshi Co., Ltd., 15W)
Cyclic voltammetry (CV): CV BAS ALS-630C (manufactured by BAS)
Scanning electron microscope (SEM): JSM6701F (manufactured by Shimadzu Corporation)
参考例１
＜Ｎ、Ｎ−ジエチルジチオカルバミルメチルスチレンの合成＞
２Ｌの反応フラスコに、クロロメチルスチレン［セイミケミカル（株）製、ＣＭＳ−１４（商品名）］１２０ｇ、Ｎ、Ｎ−ジエチルジチオカルバミド酸ナトリウム３水和物［関東化学（株）製］１８１ｇ、アセトン１４００ｇを仕込み、撹拌下、４０℃で１時間反応させた。反応後、析出した塩化ナトリウムを濾過して除き、その後エバポレーターで反応溶液からアセトンを留去させ、反応粗粉末を得た。この反応粗粉末をトルエンに再溶解させ、トルエン／水系で分液後、−２０℃の冷凍庫内でトルエン相から目的物を再結晶させた。再結晶物を濾過、真空乾燥して、白色粉末の目的物２０６ｇ（収率９７％）を得た。
Reference example 1
<Synthesis of N, N-diethyldithiocarbamylmethylstyrene>
In a 2 L reaction flask, 120 g of chloromethylstyrene [manufactured by Seimi Chemical Co., Ltd., CMS-14 (trade name)], 181 g of sodium N, N-diethyldithiocarbamate trihydrate [manufactured by Kanto Chemical Co., Ltd.], 1400 g of acetone was charged and reacted at 40 ° C. for 1 hour with stirring. After the reaction, the precipitated sodium chloride was removed by filtration, and then acetone was distilled off from the reaction solution with an evaporator to obtain a reaction crude powder. This reaction crude powder was redissolved in toluene, and after separation in a toluene / water system, the target product was recrystallized from the toluene phase in a −20 ° C. freezer. The recrystallized product was filtered and vacuum-dried to obtain 206 g (yield 97%) of the target product as a white powder.
参考例２
＜ジチオカルバメート基を分子末端に有するスチレン系ハイパーブランチポリマーの合成＞
３００ｍＬの反応フラスコに、参考例１で得られたＮ、Ｎ−ジエチルジチオカルバミルメチルスチレン１０８ｇ、トルエン７２ｇを仕込み、撹拌して淡黄色透明溶液を調製した後、反応系内を窒素置換した。この溶液の真ん中から１００Ｗの高圧水銀灯［セン特殊光源（株）製、ＨＬ−１００］を点灯させ、内部照射による光重合反応を、撹拌下、室温で１２時間行なった。次にこの反応液をメタノール３０００ｇに添加してポリマーを高粘度な塊状状態で再沈した後、上澄み液をデカンテーションで除いた。さらにこのポリマーをテトラヒドロフラン３００ｇに再溶解した後、この溶液をメタノール３０００ｇに添加してポリマーをスラリー状態で再沈した。このスラリーを濾過し、真空乾燥して、白色粉末の目的物４８ｇを得た。ゲル浸透クロマトグラフィーによるポリスチレン換算で測定される重量平均分子量Ｍｗは２０，９００、分散度Ｍｗ／Ｍｎは４．９であった。
Reference example 2
<Synthesis of Styrenic Hyperbranched Polymer Having Dithiocarbamate Group at Molecular End>
A 300 mL reaction flask was charged with 108 g of N, N-diethyldithiocarbamylmethylstyrene obtained in Reference Example 1 and 72 g of toluene and stirred to prepare a pale yellow transparent solution, and then the inside of the reaction system was purged with nitrogen. A 100 W high-pressure mercury lamp (manufactured by Sen Special Light Source Co., Ltd., HL-100) was turned on from the middle of this solution, and a photopolymerization reaction by internal irradiation was performed at room temperature for 12 hours with stirring. Next, this reaction solution was added to 3000 g of methanol to reprecipitate the polymer in a highly viscous lump state, and then the supernatant was removed by decantation. Furthermore, after this polymer was redissolved in 300 g of tetrahydrofuran, this solution was added to 3000 g of methanol to reprecipitate the polymer in a slurry state. This slurry was filtered and vacuum-dried to obtain 48 g of the desired product as a white powder. The weight average molecular weight Mw measured by gel permeation chromatography in terms of polystyrene was 20,900, and the degree of dispersion Mw / Mn was 4.9.
参考例３
＜ジチオカルバメート基を分子末端に有する直鎖状ポリ（メタクリル酸２−ヒドロキシエチル）をシェル鎖に有するコア（スチレン系）−シェル型ハイパーブランチポリマー（ＨＰＳ／ＰＨＥＭＡ）の合成＞
３００ｍＬ反応フラスコに参考例２で得られたスチレン系ハイパーブランチポリマー７９６ｍｇ、メタクリル酸２−ヒドロキシエチル３９．０ｇ、テトラエチルチウラムジスルフィド８９０ｍｇ、及びＤＭＦ１６３ｇを仕込み、撹拌して透明溶液を調製した後、反応系内を窒素置換した。この溶液の真ん中から１００Ｗの高圧水銀灯［セン特殊光源（株）製、ＨＬ−１００］を点灯させ、内部照射による光重合反応を、撹拌下で、温度３０±５℃で６時間行った。つぎにこの反応液をジイソプロピルエーテル１．５Ｌに添加してポリマーをスラリー状態で再沈した。得られた粘稠物をデカンテーションにより分別し、エタノール１００ｇに再溶解した後、この溶液をヘキサン２Ｌに添加してポリマーをスラリー状態で再沈した。このスラリーを濾過し、真空乾燥して、白色粉末の目的物１８．４ｇを得た。得られたポリマーのゲル浸透クロマトグラフィーによるポリスチレン換算で測定された重量平均分子量Ｍｗは８４，０００であり、分散度Ｍｗ／Ｍｎは３．９５であった。
得られたハイパーブランチポリマーは、下記の化学式（１０１）で表される構造を重合開始部位、化学式（１０２）で表される枝分かれ構造の繰り返し単位とし、その末端に化学式（１０３）で表される直鎖状の構造を有するハイパーブランチポリマーである。
<Synthesis of Core (Styrenic) -Shell Hyperbranched Polymer (HPS / PHEMA) Having Linear Poly (2-Hydroxyethyl Methacrylate) Having Dithiocarbamate Group at Molecular Terminal in Shell Chain>
Into a 300 mL reaction flask was charged 796 mg of the styrene-based hyperbranched polymer obtained in Reference Example 2, 39.0 g of 2-hydroxyethyl methacrylate, 890 mg of tetraethylthiuram disulfide, and 163 g of DMF and stirred to prepare a transparent solution. The inside was replaced with nitrogen. A 100 W high-pressure mercury lamp (manufactured by Sen Special Light Source Co., Ltd., HL-100) was turned on from the middle of this solution, and a photopolymerization reaction by internal irradiation was performed at a temperature of 30 ± 5 ° C. for 6 hours under stirring. Next, this reaction solution was added to 1.5 L of diisopropyl ether to reprecipitate the polymer in a slurry state. The resulting viscous material was separated by decantation and redissolved in 100 g of ethanol, and then this solution was added to 2 L of hexane to reprecipitate the polymer in a slurry state. This slurry was filtered and vacuum-dried to obtain 18.4 g of the desired product as a white powder. The weight average molecular weight Mw measured by gel permeation chromatography of the obtained polymer in terms of polystyrene was 84,000, and the degree of dispersion Mw / Mn was 3.95.
The obtained hyperbranched polymer has a structure represented by the following chemical formula (101) as a polymerization initiation site, a repeating unit of a branched structure represented by the chemical formula (102), and represented by the chemical formula (103) at the terminal. It is a hyperbranched polymer having a linear structure.
参考例４
＜分子末端が還元されたジチオカルバメート基を分子末端に有する直鎖状ポリ（メタクリル酸２−ヒドロキシエチル）をシェル鎖に有するコア（スチレン系）−シェル型ハイパーブランチポリマー（ＨＰＳ／ＰＨＥＭＡ−Ｈ）の合成＞
３００ｍＬガラス製反応フラスコに、参考例３で得たジチオカルバメート基を分子末端に有するハイパーブランチポリマー（Ｍｗ：８４，０００、Ｍｗ／Ｍｎ：３．９５）５ｇ、エタノール７０ｇを仕込み、撹拌して透明溶液を調製した後、水素化トリブチルスズ［アルドリッチ社製］１．１５ｍＬを添加した。反応系内を窒素置換し、この溶液の真ん中から１００Ｗの高圧水銀灯［セン特殊光源（株）製、ＨＬ−１００］を点灯させ、内部照射による光反応を、撹拌下、温度３０±５℃で３時間行った。次に、この反応溶液をヘキサン１Ｌに添加して、ハイパーブランチポリマーをスラリー状態で再沈した。この再沈を３回繰り返した後、得られたスラリーを濾過し、真空乾燥して、白色粉末のジチオカルバメート基が水素に置換されたハイパーブランチポリマー３．９ｇを得た。ゲル浸透クロマトグラフィーによるポリスチレン換算で測定される重量平均分子量Ｍｗは１１６，０００、分散度Ｍｗ／Ｍｎは３．４３であった。得られたハイパーブランチポリマーをＤＭＦへ溶解させ、２００μｇ／ｍＬとなるように調整した溶液の紫外可視吸収スペクトル測定結果を図１（還元後）に示した。還元反応前に観測されたジチオカルバメート基に由来する
２８０ｎｍを中心とするピークが、還元反応後消失しているのが観測された。これより得られたハイパーブランチポリマーは、上記の化学式（１０１）で表される構造式を重合開始部位とし、上記の化学式（１０２）で表される枝分れ構造の繰り返し単位と上記の化学式（１０３）で表される直鎖構造の繰り返し単位を有するハイパーブランチポリマーのジチオカルバメート基が還元されたハイパーブランチポリマーである。
Reference example 4
<Core (styrene-based) -shell hyperbranched polymer (HPS / PHEMA-H) having a linear poly (2-hydroxyethyl methacrylate) having a dithiocarbamate group reduced at the molecular end at the molecular end in the shell chain Synthesis>
A 300 mL glass reaction flask was charged with 5 g of a hyperbranched polymer (Mw: 84,000, Mw / Mn: 3.95) having a dithiocarbamate group obtained in Reference Example 3 at the molecular end and 70 g of ethanol, and stirred to be transparent. After preparing the solution, 1.15 mL of tributyltin hydride [manufactured by Aldrich] was added. The reaction system was purged with nitrogen, and a 100 W high pressure mercury lamp (manufactured by Sen Special Light Source Co., Ltd., HL-100) was turned on from the middle of this solution, and the photoreaction by internal irradiation was performed at a temperature of 30 ± 5 ° C. with stirring. I went for 3 hours. Next, this reaction solution was added to 1 L of hexane to reprecipitate the hyperbranched polymer in a slurry state. After this reprecipitation was repeated three times, the resulting slurry was filtered and dried under vacuum to obtain 3.9 g of a hyperbranched polymer in which the dithiocarbamate group of the white powder was replaced with hydrogen. The weight average molecular weight Mw measured by gel permeation chromatography in terms of polystyrene was 116,000, and the degree of dispersion Mw / Mn was 3.43. The obtained hyperbranched polymer was dissolved in DMF, and the ultraviolet-visible absorption spectrum measurement result of a solution adjusted to 200 μg / mL is shown in FIG. 1 (after reduction). It was observed that the peak centered at 280 nm derived from the dithiocarbamate group observed before the reduction reaction disappeared after the reduction reaction. The hyperbranched polymer thus obtained has the structural formula represented by the chemical formula (101) as a polymerization initiation site, the repeating unit of the branched structure represented by the chemical formula (102) and the chemical formula ( 103). A hyperbranched polymer in which a dithiocarbamate group of a hyperbranched polymer having a linear repeating unit represented by formula (103) is reduced.
参考例５
＜Ｎ、Ｎ−ジエチルジチオカルバミルエチルメタクリレートの合成＞
２Ｌの反応フラスコに、クロロエチルメタクリレート［ランカスター社製］１００ｇ、Ｎ、Ｎ−ジエチルジチオカルバミド酸ナトリウム３水和物［関東化学（株）製］１７８ｇ、アセトン１１００ｇを仕込み、撹拌下で、温度４０℃で１４時間反応させた。反応後、析出した塩化ナトリウムを濾過して除き、その後エバポレーターで反応溶液からアセトンを留去させ、反応粗粉末を得た。この反応粗粉末を１，２−ジクロロエタンに再溶解させ、１，２−ジクロロエタン／水系で分液後、１，２−ジクロロエタン相から１，２−ジクロロエタンを留去させて黄色液体の目的物１７１ｇ（収率９７％）を得た。液体クロマトグラフィーによる純度（相対面積百分率）は９６％であった。
Reference Example 5
<Synthesis of N, N-diethyldithiocarbamylethyl methacrylate>
A 2 L reaction flask was charged with 100 g of chloroethyl methacrylate [manufactured by Lancaster], 178 g of sodium N, N-diethyldithiocarbamate trihydrate [manufactured by Kanto Chemical Co., Ltd.], and 1100 g of acetone, and stirred at a temperature of 40. The reaction was carried out at ° C for 14 hours. After the reaction, the precipitated sodium chloride was removed by filtration, and then acetone was distilled off from the reaction solution with an evaporator to obtain a reaction crude powder. This reaction crude powder was redissolved in 1,2-dichloroethane, and after separation in a 1,2-dichloroethane / water system, 1,2-dichloroethane was distilled off from the 1,2-dichloroethane phase to give 171 g of the desired product as a yellow liquid. (Yield 97%) was obtained. The purity (relative area percentage) by liquid chromatography was 96%.
参考例６
＜ジチオカルバメート基を分子末端に有するアクリル系ハイパーブランチポリマーの合成＞
３００ｍＬの反応フラスコに、参考例５で得られたＮ、Ｎ−ジエチルジチオカルバミルエチルメタクリレート９０ｇ、トルエン９０ｇを仕込み、撹拌して淡黄色透明溶液を調製した後、反応系内を窒素置換した。この溶液の真ん中から１００Ｗの高圧水銀灯［セン特殊光源（株）製、ＨＬ−１００］を点灯させ、内部照射による光重合反応を、撹拌下、室温で５時間行った。次にこの反応液をメタノール３０００ｇに添加してポリマーを高粘度な塊状状態で再沈した後、上澄み液をデカンテーションで除いた。さらにこのポリマーをテトラヒドロフラン４００ｇに再溶解した後、この溶液をメタノール５０００ｇに添加してポリマーをスラリー状態で再沈した。このスラリーを濾過し、真空乾燥して、白色粉末の目的物４４ｇを得た。ゲル浸透クロマトグラフィーによるポリスチレン換算で測定される重量平均分子量Ｍｗは４３，２００、分散度Ｍｗ／Ｍｎは２．９であった。元素分析は、炭素５０．８％、水素７．６％、窒素５．１％、硫黄２５．６％であった。熱重量分析より５％重量減少温度は１８６℃であった。
Reference Example 6
<Synthesis of acrylic hyperbranched polymer having dithiocarbamate group at molecular end>
A 300 mL reaction flask was charged with 90 g of N, N-diethyldithiocarbamylethyl methacrylate and 90 g of toluene obtained in Reference Example 5 and stirred to prepare a pale yellow transparent solution, and then the inside of the reaction system was purged with nitrogen. A 100 W high-pressure mercury lamp (manufactured by Sen Special Light Source Co., Ltd., HL-100) was turned on from the middle of this solution, and a photopolymerization reaction by internal irradiation was performed at room temperature for 5 hours with stirring. Next, this reaction solution was added to 3000 g of methanol to reprecipitate the polymer in a highly viscous lump state, and then the supernatant was removed by decantation. Further, this polymer was redissolved in 400 g of tetrahydrofuran, and then this solution was added to 5000 g of methanol to reprecipitate the polymer in a slurry state. This slurry was filtered and vacuum-dried to obtain 44 g of the desired product as a white powder. The weight average molecular weight Mw measured by gel permeation chromatography in terms of polystyrene was 43,200, and the degree of dispersion Mw / Mn was 2.9. Elemental analysis was 50.8% carbon, 7.6% hydrogen, 5.1% nitrogen, and 25.6% sulfur. From the thermogravimetric analysis, the 5% weight loss temperature was 186 ° C.
参考例７（ビタミンＢ12誘導体の合成）
ビタミンＢ12誘導体を以下に示す操作で合成し、１つのカルボキシル基を有する（ＣＮ）2Ｃｏｂ（ＩＩＩ）６Ｃ1エステルを得た。
シアノコバラミン２．５ｇ（１．９ｘ１０-3 ｍｏｌ）のメタノール溶液３００ｍＬに
９８％冷濃硫酸３０ｍＬを滴下した。遮光条件下、窒素雰囲気下で１２０時間加熱還流した。反応混合物を減圧濃縮し、冷水１００ｍＬを加えた後、固体炭酸ナトリウムで中和し、シアン化カリウム１．０ｇ（１．５ｘ１０-2 ｍｏｌ）を加えた。四塩化炭素（１００
ｍＬｘ２）、塩化メチレン（１００ｍＬｘ２）の順に抽出を行い、塩化メチレン抽出液を水（１００ｍＬｘ２）で洗浄し、硫酸ナトリウムで乾燥後、減圧乾固した。ベンゼン／ｎ−へキサンで再沈殿を行い、紫色粉末（９１４ｍｇ 収率４５％）を得た。
Reference Example 7 (Synthesis of vitamin B 12 derivative)
A vitamin B 12 derivative was synthesized by the following procedure to obtain (CN) 2 Cob (III) 6C 1 ester having one carboxyl group.
30 mL of 98% cold concentrated sulfuric acid was added dropwise to 300 mL of a methanol solution of 2.5 g (1.9 × 10 −3 mol) of cyanocobalamin. The mixture was refluxed for 120 hours under a nitrogen atmosphere under light-shielding conditions. The reaction mixture was concentrated under reduced pressure, 100 mL of cold water was added, neutralized with solid sodium carbonate, and 1.0 g (1.5 × 10 −2 mol) of potassium cyanide was added. Carbon tetrachloride (100
Extraction was performed in the order of mL × 2) and methylene chloride (100 mL × 2), and the methylene chloride extract was washed with water (100 mL × 2), dried over sodium sulfate, and then dried under reduced pressure. Reprecipitation was performed with benzene / n-hexane to obtain a purple powder (914 mg, yield 45%).
参考例８
＜ジチオカルバメート基を分子末端に有するアクリル系共重合型ハイパーブランチポリマー（ＨＰＥＭＡ−ＨＥＭＡ）の合成＞
３００ｍＬの反応フラスコに、参考例５で得られたＮ、Ｎ−ジエチルジチオカルバミルエチルメタクリレート１８．３ｇ、メタクリル酸２−ヒドロキシエチル９．１１ｇ、ＴＨＦ１５５．３ｇを仕込み、撹拌して淡黄色透明溶液を調製した後、反応系内を窒素置換し
た。この溶液の真ん中から１００Ｗの高圧水銀灯［セン特殊光源（株）製、ＨＬ−１００］を点灯させ、内部照射による光重合反応を、撹拌下、室温で８時間行った。次にこの反応液をヘキサン１０００ｇに添加してポリマーをスラリー状態で再沈したした。これを濾過し、湿品を再度テトラヒドロフラン１５０ｇに再溶解した後、この溶液をメタノール１０００ｇに添加してポリマーをスラリー状態で再沈した。このスラリーを濾過し、真空乾燥して、白色粉末の目的物１２ｇを得た。ゲル浸透クロマトグラフィーによるポリスチレン換算で測定される重量平均分子量Ｍｗは３０，０００、分散度Ｍｗ／Ｍｎは２．８６であった。また絶対分子量をＧＰＣ―ＭＡＬＳより測定したところ、Ｍｗは５３,０００で
あり、本ハイパーブランチポリマーの分岐度は絶対分子量と相対分子量の比（ＭＡＬＳ／ＧＰＣ比）より、１．７７であった。１Ｈ−ＮＭＲスペクトルを図２に示す。
Reference Example 8
<Synthesis of an acrylic copolymer hyperbranched polymer (HPEMA-HEMA) having a dithiocarbamate group at the molecular end>
A 300 mL reaction flask was charged with 18.3 g of N, N-diethyldithiocarbamylethyl methacrylate obtained in Reference Example 5, 9.11 g of 2-hydroxyethyl methacrylate, and 155.3 g of THF, and stirred to obtain a pale yellow transparent solution. Was prepared, and the reaction system was purged with nitrogen. A 100 W high-pressure mercury lamp (manufactured by Sen Special Light Source Co., Ltd., HL-100) was turned on from the middle of this solution, and a photopolymerization reaction by internal irradiation was performed at room temperature for 8 hours with stirring. Next, this reaction solution was added to 1000 g of hexane to reprecipitate the polymer in a slurry state. This was filtered and the wet product was redissolved again in 150 g of tetrahydrofuran, and this solution was added to 1000 g of methanol to reprecipitate the polymer in a slurry state. This slurry was filtered and vacuum-dried to obtain 12 g of the desired product as a white powder. The weight average molecular weight Mw measured by gel permeation chromatography in terms of polystyrene was 30,000, and the degree of dispersion Mw / Mn was 2.86. When the absolute molecular weight was measured by GPC-MALS, Mw was 53,000, and the degree of branching of the hyperbranched polymer was 1.77 from the ratio of absolute molecular weight to relative molecular weight (MALS / GPC ratio). The 1H-NMR spectrum is shown in FIG.
参考例９
＜ジチオカルバメート基を分子末端に有するアクリル系共重合型ハイパーブランチポリマー（ＨＰＳ−ＨＥＭＡ）の合成＞
３００ｍＬの反応フラスコに、参考例１で得られたＮ、Ｎ−ジエチルジチオカルバミルメチルスチレン（Ｓ−ＤＣ）２５．２２ｇ、メタクリル酸２−ヒドロキシエチル（ＨＥＭＡ）１２．３６ｇ、ＰＧＭＥＡ７６．３を仕込み、撹拌して淡黄色透明溶液を調製した後、反応系内を窒素置換した。この溶液の真ん中から１００Ｗの高圧水銀灯［セン特殊光源（株）製、ＨＬ−１００］を点灯させ、内部照射による光重合反応を、撹拌下、室温で７時間行った。次にこの反応液をヘキサン１０００ｇに添加してポリマーをスラリー状態で再沈したした。これを濾過し、湿品を再度テトラヒドロフラン１５０ｇに再溶解した後、この溶液をジイソプロピルエーテル１０００ｇに添加してポリマーをスラリー状態で再沈した。このスラリーを濾過し、真空乾燥して、白色粉末の目的物１５ｇを得た。ゲル浸透クロマトグラフィーによるポリスチレン換算で測定される重量平均分子量Ｍｗは３０，０００、分散度Ｍｗ／Ｍｎは５．４であった。また13Ｃ−ＮＭＲ測定（ＮＭＲ ＥＣＡ７０
０、ＪＥＯＬ）より、本ハイパーブランチポリマーの組成比は、Ｓ−ＤＣ：ＨＥＭＡ＝１：１．１であった（図３）。
Reference Example 9
<Synthesis of an acrylic copolymer hyperbranched polymer (HPS-HEMA) having a dithiocarbamate group at the molecular end>
A 300 mL reaction flask was charged with 25.22 g of N, N-diethyldithiocarbamylmethylstyrene (S-DC) obtained in Reference Example 1, 12.36 g of 2-hydroxyethyl methacrylate (HEMA) and 76.3 PGMEA. After stirring, a pale yellow transparent solution was prepared, and the reaction system was purged with nitrogen. A 100 W high-pressure mercury lamp (manufactured by Sen Special Light Source Co., Ltd., HL-100) was turned on from the middle of this solution, and a photopolymerization reaction by internal irradiation was performed at room temperature for 7 hours with stirring. Next, this reaction solution was added to 1000 g of hexane to reprecipitate the polymer in a slurry state. This was filtered and the wet product was redissolved again in 150 g of tetrahydrofuran, and this solution was added to 1000 g of diisopropyl ether to reprecipitate the polymer in a slurry state. This slurry was filtered and vacuum-dried to obtain 15 g of the desired product as a white powder. The weight average molecular weight Mw measured by gel permeation chromatography in terms of polystyrene was 30,000, and the degree of dispersion Mw / Mn was 5.4. 13 C-NMR measurement (NMR ECA70
0, JEOL), the composition ratio of the hyperbranched polymer was S-DC: HEMA = 1: 1.1 (FIG. 3).
実施例１
＜ジチオカルバメート基を分子末端に有する直鎖状ポリ（メタクリル酸２−ヒドロキシエチル）をシェル鎖に有するコア（アクリル系）−シェル型ハイパーブランチポリマー（ＨＰＥＭＡ／ＰＨＥＭＡ）の合成＞
３００ｍＬ反応フラスコに参考例６で得られたアクリル系ハイパーブランチポリマー７９０ｍｇ、メタクリル酸２−ヒドロキシエチル３９．２ｇ、テトラエチルチウラムジスルフィド８９３ｍｇ、及びＤＭＦ１６０ｇを仕込み、撹拌して淡黄色透明溶液を調製した後、反応系内を窒素置換した。この溶液の真ん中から１００Ｗの高圧水銀灯［セン特殊光源（株）製、ＨＬ−１００］を点灯させ、内部照射による光重合反応を、撹拌下で、温度３０±５℃で１２時間行った。つぎにこの反応液をＴＨＦ４００ｇ−ヘキサン６００ｇの混合溶液に添加してポリマーをスラリー状態で再沈した。得られた粘稠物をデカンテーションにより分別し、４０℃温浴下２−プロパノール１００ｇに再溶解した後、この溶液をヘキサン１，０００ｇに添加してポリマーをスラリー状態で再沈した。このスラリーを濾過し、真空乾燥して、白色粉末の目的物１１．０ｇを得た。得られたポリマーのゲル浸透クロマトグラフィーによるポリスチレン換算で測定された重量平均分子量Ｍｗは６０，０００であり、分散度Ｍｗ／Ｍｎは４．７８であった。
得られたハイパーブランチポリマーは、下記の化学式（１０４）で表される構造式を重合開始部位、化学式（１０５）で表される枝分かれ構造の繰り返し単位とし、その末端に化学式（１０６）で表される直鎖状の構造を有するハイパーブランチポリマーである。
<Synthesis of a core (acrylic) -shell hyperbranched polymer (HPEMA / PHEMA) having a linear poly (2-hydroxyethyl methacrylate) having a dithiocarbamate group at a molecular end in a shell chain>
After preparing 790 mg of the acrylic hyperbranched polymer obtained in Reference Example 6, 39.2 g of 2-hydroxyethyl methacrylate, 893 mg of tetraethylthiuram disulfide, and 160 g of DMF in a 300 mL reaction flask, stirring to prepare a pale yellow transparent solution, The reaction system was purged with nitrogen. A 100 W high-pressure mercury lamp (manufactured by Sen Special Light Source Co., Ltd., HL-100) was turned on from the middle of this solution, and a photopolymerization reaction by internal irradiation was performed at a temperature of 30 ± 5 ° C. for 12 hours under stirring. Next, this reaction solution was added to a mixed solution of THF 400 g-hexane 600 g to reprecipitate the polymer in a slurry state. The resulting viscous material was fractionated by decantation and redissolved in 100 g of 2-propanol in a 40 ° C. warm bath, and then this solution was added to 1,000 g of hexane to reprecipitate the polymer in a slurry state. This slurry was filtered and vacuum-dried to obtain 11.0 g of the desired product as a white powder. The weight average molecular weight Mw measured by gel permeation chromatography of the obtained polymer in terms of polystyrene was 60,000, and the degree of dispersion Mw / Mn was 4.78.
The obtained hyperbranched polymer has a structural formula represented by the following chemical formula (104) as a polymerization initiation site, a repeating unit of a branched structure represented by the chemical formula (105), and is represented by the chemical formula (106) at the terminal. It is a hyperbranched polymer having a linear structure.
実施例２
＜分子末端が還元されたジチオカルバメート基を分子末端に有する直鎖状ポリ（メタクリル酸２−ヒドロキシエチル）をシェル鎖に有するコア（アクリル系）−シェル型ハイパーブランチポリマー（ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ）の合成＞
３００ｍＬガラス製反応フラスコに、実施例１で得たジチオカルバメート基を分子末端に有するハイパーブランチポリマー（Ｍｗ：６０，０００、Ｍｗ／Ｍｎ：４．７８）４ｇ、エタノール１５６ｇを仕込み、撹拌してうす黄色透明溶液を調製した後、水素化トリブ
チルスズ［アルドリッチ社製］９．７ｍＬを添加した。反応系内を窒素置換し、この溶液の真ん中から１００Ｗの高圧水銀灯［セン特殊光源（株）製、ＨＬ−１００］を点灯させ、内部照射による光反応を、撹拌下、温度３０±５℃で３時間行った。次に、この反応溶液をヘキサン１Ｌに添加して、ハイパーブランチポリマーをスラリー状態で再沈した。この再沈を３回繰り返した後、得られたスラリーを濾過し、真空乾燥して、白色粉末のジチオカルバメート基が水素に置換されたハイパーブランチポリマー２．８ｇを得た。ゲル浸透クロマトグラフィーによるポリスチレン換算で測定される重量平均分子量Ｍｗは５９，０００、分散度Ｍｗ／Ｍｎは４．４５であった。得られたハイパーブランチポリマーをＤＭＦへ溶解させ、２５０μｇ／ｍＬとなるように調整した溶液の紫外可視吸収スペクトル測定結果を図４（還元後）に示した。還元反応前に観測されたジチオカルバメート基に由来する２８０ｎｍを中心とするピークが、還元反応後消失しているのが観測された。これより得られたハイパーブランチポリマーは、上記の化学式（１０４）で表される構造式を重合開始部位とし、上記の化学式（１０５）で表される枝分れ構造の繰り返し単位と上記の化学式（１０６）で表される直鎖構造の繰り返し単位を有するハイパーブランチポリマーのジチオカルバメート基が還元されたハイパーブランチポリマーである。
Example 2
<Core (acrylic) -shell hyperbranched polymer (HPEMA / PHEMA-H) having a linear poly (2-hydroxyethyl methacrylate) having a dithiocarbamate group reduced at the molecular end at the molecular end in the shell chain Synthesis>
A 300 mL glass reaction flask was charged with 4 g of the hyperbranched polymer (Mw: 60,000, Mw / Mn: 4.78) having the dithiocarbamate group obtained in Example 1 at the molecular end and 156 g of ethanol, and the mixture was stirred. After preparing a yellow transparent solution, 9.7 mL of tributyltin hydride [manufactured by Aldrich] was added. The reaction system was purged with nitrogen, and a 100 W high pressure mercury lamp (manufactured by Sen Special Light Source Co., Ltd., HL-100) was turned on from the middle of this solution, and the photoreaction by internal irradiation was performed at a temperature of 30 ± 5 ° C. with stirring. I went for 3 hours. Next, this reaction solution was added to 1 L of hexane to reprecipitate the hyperbranched polymer in a slurry state. After repeating this reprecipitation three times, the resulting slurry was filtered and dried under vacuum to obtain 2.8 g of a hyperbranched polymer in which the dithiocarbamate group of the white powder was replaced with hydrogen. The weight average molecular weight Mw measured by gel permeation chromatography in terms of polystyrene was 59,000, and the degree of dispersion Mw / Mn was 4.45. The obtained hyperbranched polymer was dissolved in DMF, and the results of measuring the ultraviolet-visible absorption spectrum of the solution adjusted to 250 μg / mL are shown in FIG. 4 (after reduction). It was observed that the peak centered at 280 nm derived from the dithiocarbamate group observed before the reduction reaction disappeared after the reduction reaction. The hyperbranched polymer thus obtained has the structural formula represented by the chemical formula (104) as a polymerization initiation site, the repeating unit of the branched structure represented by the chemical formula (105) and the chemical formula ( 106) is a hyperbranched polymer in which the dithiocarbamate group of the hyperbranched polymer having a linear repeating unit represented by formula (106) is reduced.
実施例３
＜コアシェル型ＨＢＰ（ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ）へのビタミンＢ12誘導体の化学修飾＞
２５ｍＬ二口ナス型フラスコにビタミンＢ12誘導体（（ＣＮ）2Ｃｏｂ（ＩＩＩ）６Ｃ1エステル）８０．３ｍｇ（７．４７×１０-5ｍｏｌ）、コアシェル型ハイパーブランチポリマー（ＨＢＰ）として実施例２で得られたＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ（１０４．８ｍｇ（含ＯＨ基７．８９×１０-4ｍｏｌ）、４−ジメチルアミノピリジン（ＤＭＡＰ）４７．４ｍｇ（３．８８×１０-4ｍｏｌ）を入れ、窒素置換した。乾燥Ｎ，Ｎ−ジメチルホルムアミド（ＤＭＦ）溶液（３ｍＬ）を加え溶解させた後、氷浴下で１−エチル−３−（３−ジメチルアミノプロピル）−カルボジイミド（ＥＤＣ／ＨＣｌ）７３．０ｍｇ（３．８１×１０-4ｍｏｌ）を加え、室温で４時間撹拌した。その後、クロロホルム１００ｍＬを加え蒸留水で３回洗浄した。無水硫酸ナトリウムで脱水後、溶液を濃縮し、ＧＰＣ（溶離液クロロホルム、３７１ｎｍ検出波長）により精製した。分取した第一成分（ブロード）にシアン化カリウム（ＫＣＮ）水溶液（ＫＣＮ７６．０ｍｇ（１．１７×１０-3 ｍｏｌ）、水１００ｍＬ）を加え分液漏斗で激しく振とうし、蒸留水で３回洗浄した。無水硫酸ナトリウムで脱水後、溶媒を減圧留去してクロロホルム／ｎ−ヘキサンで再沈殿した。生成物をろ過、減圧乾燥し紫色粉末を得た。
収量 ８６．５ｍｇ 修飾率 ６．６％
Ｂ12‐ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ １ｇ当りのＢ12の固定化量 ３４９ｍｇ
ＧＰＣチャートを図５に示す。ビタミンＢ12誘導体修飾後のＵＶ−ｖｉｓスペクトルを図６に、1Ｈ−ＮＭＲスペクトルを図７に示す。
Example 3
<Chemical modification of vitamin B 12 derivatives of the core-shell HBP (HPEMA / PHEMA-H) >
Yield 86.5 mg Modification 6.6%
B 12 -HPEMA / PHEMA-H immobilization amount 349mg of 1g per B 12
A GPC chart is shown in FIG. FIG. 6 shows a UV-vis spectrum after modification with a vitamin B 12 derivative, and FIG. 7 shows a 1 H-NMR spectrum.
実施例４
＜コアシェル型ＨＢＰ（ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ）へのビタミンＢ12誘導体の化学修飾＞
ビタミンＢ12誘導体の仕込み量：０．２当量
ビタミンＢ12誘導体６３．４ｍｇ（５．９０×１０-5ｍｏｌ）、コアシェル型ＨＢＰとして実施例２で得られたＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ４０．７ｍｇ（含ＯＨ基３．０６×１０-4ｍｏｌ）、ＥＤＣ／ＨＣｌ５６．７ｍｇ（２．９６×１０-4ｍｏｌ）、ＤＭＡＰ３６．２ｍｇ（２．９６×１０-4ｍｏｌ）を用いて実施例３と同様の操作を行った。
収量 ４２．５ｍｇ 修飾率 ７．２％
Ｂ12‐ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ １ｇ当りのＢ12の固定化量 ３６８ｍｇ
Example 4
<Chemical modification of vitamin B 12 derivatives of the core-shell HBP (HPEMA / PHEMA-H) >
Charged amount of vitamin B 12 derivative: 0.2 eq vitamin B 12 derivative 63.4mg (5.90 × 10 -5 mol) , HPEMA obtained in Example 2 as a core-shell HBP / PHEMA-H40.7mg (including OH group 3.06 × 10 −4 mol), EDC / HCl 56.7 mg (2.96 × 10 −4 mol), DMAP 36.2 mg (2.96 × 10 −4 mol) The operation was performed.
Yield 42.5mg Modification rate 7.2%
B 12 -HPEMA / PHEMA-H Immobilization amount of B 12 per gram 368 mg
実施例５
＜コアシェル型ＨＢＰ（ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ）へのビタミンＢ12誘導体の化学修飾＞
ビタミンＢ12誘導体の仕込み量：０．３当量
ビタミンＢ12誘導体３０．８ｍｇ（２．８６×１０-5ｍｏｌ）、コアシェル型ＨＢＰとして実施例２で得られたＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ７３．３ｍｇ（含ＯＨ基５．５２×１０-4ｍｏｌ）、ＥＤＣ／ＨＣｌ４９．１ｍｇ（２．５６×１０-4ｍｏｌ）、ＤＭＡＰ２９．５ｍｇ（２．４１×１０-4ｍｏｌ）を用いて実施例３と同様の操作を行った。
収量 ４４．４ｍｇ 修飾率 １１．４％
Ｂ12‐ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ １ｇ当りのＢ12の固定化量 ４８１ｍｇ
Example 5
<Chemical modification of vitamin B 12 derivatives of the core-shell HBP (HPEMA / PHEMA-H) >
Charged amount of vitamin B 12 derivative: 0.3 eq vitamin B 12 derivative 30.8mg (2.86 × 10 -5 mol) , HPEMA obtained in Example 2 as a core-shell HBP / PHEMA-H73.3mg (including OH group 5.52 × 10 −4 mol), EDC / HCl 49.1 mg (2.56 × 10 −4 mol), DMAP 29.5 mg (2.41 × 10 −4 mol) The operation was performed.
Yield 44.4 mg Modification rate 11.4%
B 12 -HPEMA / PHEMA-H immobilization amount 481mg of 1g per B 12
実施例６
＜コアシェル型ＨＢＰ（ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ）へのビタミンＢ12誘導体の化学修飾＞
ビタミンＢ12誘導体の仕込み量：０．４当量
ビタミンＢ12誘導体１２６．３ｍｇ（１．１７×１０-4ｍｏｌ）、コアシェル型ＨＢＰとして実施例２で得られたＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ４０．７ｍｇ（含ＯＨ基３．０６×１０-4ｍｏｌ）、ＥＤＣ／ＨＣｌ５９．５ｍｇ（３．１０×１０-4ｍｏｌ）、ＤＭＡＰ３６．３ｍｇ（２．９７×１０-4ｍｏｌ）を用いて実施例３と同様の操作を行った。収量
７５．６ｍｇ 修飾率 １５．６％
Ｂ12‐ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ １ｇ当りのＢ12の固定化量 ５５７ｍｇ
Example 6
<Chemical modification of vitamin B 12 derivatives of the core-shell HBP (HPEMA / PHEMA-H) >
Charged amount of vitamin B 12 derivative: 0.4 eq vitamin B 12 derivative 126.3mg (1.17 × 10 -4 mol) , HPEMA obtained in Example 2 as a core-shell HBP / PHEMA-H40.7mg (including OH group 3.06 × 10 −4 mol), EDC / HCl 59.5 mg (3.10 × 10 −4 mol), DMAP 36.3 mg (2.97 × 10 −4 mol) The operation was performed. Yield 75.6 mg Modification rate 15.6%
B 12 -HPEMA / PHEMA-H Immobilization amount of B 12 per 1 g 557 mg
実施例７
＜コアシェル型ＨＢＰ（ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ）へのビタミンＢ12誘導体の化学修飾＞
ビタミンＢ12誘導体の仕込み量：０．７当量
ビタミンＢ12誘導体１１３．４ｍｇ（１．０５×１０-4ｍｏｌ）、コアシェル型ＨＢＰとして実施例２で得られたＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ２０．７ｍｇ（含ＯＨ基１．５６×１０-4ｍｏｌ）、ＥＤＣ／ＨＣｌ８７．３ｍｇ（４．５５×１０-4ｍｏｌ）、ＤＭＡＰ５５．５ｍｇ（４．５４×１０-4ｍｏｌ）を用いて実施例３と同様の操作を行った。
収量 ４１．６ｍｇ 修飾率 ２０．２％
Ｂ12‐ＨＰＥＭＡ／ＰＨＥＭＡ１ｇ当りのＢ12の固定化量 ６２０ｍｇ
Example 7
<Chemical modification of vitamin B 12 derivatives of the core-shell HBP (HPEMA / PHEMA-H) >
Charged amount of vitamin B 12 derivative: 0.7 eq vitamin B 12 derivative 113.4mg (1.05 × 10 -4 mol) , HPEMA / PHEMA-H20.7mg obtained in Example 2 as a core-shell type HBP (including OH group 1.56 × 10 −4 mol), EDC / HCl 87.3 mg (4.55 × 10 −4 mol), DMAP 55.5 mg (4.54 × 10 −4 mol) The operation was performed.
Yield 41.6 mg Modification rate 20.2%
Immobilization amount of B 12 per gram of B 12 -HPEMA / PHEMA 620 mg
実施例８
＜コアシェル型ＨＢＰ（ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ）へのビタミンＢ12誘導体の化学修飾＞
ビタミンＢ12誘導体の仕込み量：１．０当量
ビタミンＢ12誘導体１６２．１ｍｇ（１．５１×１０-4ｍｏｌ）、コアシェル型ＨＢＰとして実施例１で得られたＨＰＥＭＡ／ＰＨＥＭＡ２１．９ｍｇ（含ＯＨ基１．６５×１０-4ｍｏｌ）、ＥＤＣ／ＨＣｌ１４９．７ｍｇ（７．８１×１０-4ｍｏｌ）、ＤＭＡＰ９３．５ｍｇ（７．６５×１０-4ｍｏｌ）を用いて実施例３と同様の操作を行った。
収量 ４９．４ｍｇ 修飾率 １９．３％
Ｂ12‐ＨＰＥＭＡ／ＰＨＥＭＡ１ｇ当りのＢ12の固定化量 ６１０ｍｇ
Example 8
<Chemical modification of vitamin B 12 derivatives of the core-shell HBP (HPEMA / PHEMA-H) >
Charged amount of vitamin B 12 derivative: 1.0 eq vitamin B 12 derivative 162.1mg (1.51 × 10 -4 mol) , HPEMA obtained in Example 1 as a core-shell HBP / PHEMA21.9mg (including OH group 1.65 × 10 −4 mol), EDC / HCl 149.7 mg (7.81 × 10 −4 mol), DMAP 93.5 mg (7.65 × 10 −4 mol), and the same operation as in Example 3. went.
Yield 49.4 mg Modification rate 19.3%
Immobilization amount of B 12 per gram of B 12 -HPEMA / PHEMA 610 mg
実施例９
＜コアシェル型ＨＢＰ（ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ）へのビタミンＢ12誘導体の化学修飾＞
ビタミンＢ12誘導体の仕込み量：０．０５当量
２５ｍＬ二口ナス型フラスコにビタミンＢ12誘導体４０．２ｍｇ（３．７４×１０-5ｍｏｌ）、コアシェル型ＨＢＰとして実施例２で得られたＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ１００．５ｍｇ（含ＯＨ基７．５７×１０-4ｍｏｌ）、ＤＭＡＰ４４．８ｍｇ（３．６７×１０-4ｍｏｌ）を入れ、窒素置換した。乾燥ＤＭＦ溶液（３ｍＬ）を加え溶解させた後、氷浴下でＥＤＣ／ＨＣｌ７８．２ｍｇ（４．０８×１０-4ｍｏｌ）を加え、４時間撹拌した。その後、クロロホルム１００ｍＬを加え蒸留水で３回洗浄した。無水硫酸ナトリウムで脱水後、溶媒を減圧留去し、メタノールに溶解させカラム（Ｓｅｐｈａｄｅｘ ＬＨ−２０）で精製した。分取した第一成分を濃縮し、クロロホルムを加えた後、ＫＣＮ水溶液（ＫＣＮ４３．６ｍｇ（６．７０×１０-4 ｍｏｌ）、水１００ｍＬ）を加え分液漏斗で激しく振とうし、蒸留水で３回洗浄した。析出した紫色固体はメタノールに溶解させて有機相に加え無水硫酸ナトリウムで脱水後、溶媒を減圧留去、乾固して紫色固体を得た。
収量 ２６．６ｍｇ 修飾率 １．９％
Ｂ12‐ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ １ｇ当りのＢ12の固定化量１３０ｍｇ
表１に実施例３ないし９のビタミンＢ12誘導体の仕込み比と修飾率、固定化量をまとめたものを示す。また、図８にビタミンＢ12誘導体の仕込み比と修飾率の相関を示す。
<Chemical modification of vitamin B 12 derivatives of the core-shell HBP (HPEMA / PHEMA-H) >
Preparation amount of vitamin B 12 derivative: 0.05 equivalent In a 25 mL two-necked eggplant type flask, 40.2 mg (3.74 × 10 −5 mol) of vitamin B 12 derivative, HPEMA / obtained in Example 2 as core-shell type HBP PHEMA-H 100.5 mg (OH-containing group 7.57 × 10 −4 mol) and DMAP 44.8 mg (3.67 × 10 −4 mol) were added, and the atmosphere was replaced with nitrogen. After adding and dissolving a dry DMF solution (3 mL), 78.2 mg (4.08 × 10 −4 mol) of EDC / HCl was added in an ice bath, and the mixture was stirred for 4 hours. Thereafter, 100 mL of chloroform was added and washed 3 times with distilled water. After dehydration with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, dissolved in methanol and purified with a column (Sephadex LH-20). The separated first component was concentrated, chloroform was added, KCN aqueous solution (KCN 43.6 mg (6.70 × 10 −4 mol), water 100 mL) was added, and the mixture was vigorously shaken with a separatory funnel, and then with distilled water. Washed 3 times. The deposited purple solid was dissolved in methanol, added to the organic phase, dehydrated with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was dried to obtain a purple solid.
Yield 26.6 mg Modification rate 1.9%
Immobilization amount of B 12 per gram of B 12 -HPEMA / PHEMA-H 130 mg
Table 1 summarizes the charging ratio, modification rate, and amount of immobilization of the vitamin B 12 derivatives of Examples 3 to 9. FIG. 8 shows the correlation between the preparation ratio of vitamin B 12 derivative and the modification rate.
実施例１０
＜Ｂ12‐ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈのミクロ環境評価＞
実施例６で合成したＢ12‐ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ（修飾率１５．６％）を種々の溶媒に溶解し、それぞれＵＶ−ｖｉｓスペクトルを測定した。また、ビタミンＢ12誘導体を用いて同様の操作を行った。表２に種々の溶媒中でのＢ12‐ＨＰＥＭＡ／ＰＨＥＭＡ−
Ｈ及びビタミンＢ12誘導体のα帯の吸収極大波数を示す。図９にＢ12‐ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ及びビタミンＢ12誘導体のα帯の吸収極大波数と溶媒の極性パラメータＥT Nとの相関を示す
<Microenvironment evaluation of B 12 -HPEMA / PHEMA-H>
B 12 -HPEMA / PHEMA-H (modified rate 15.6%) synthesized in Example 6 was dissolved in various solvents, and UV-vis spectra were measured respectively. Further, the same operation was carried out by using vitamin B 12 derivatives. Table 2 shows B 12 -HPEMA / PHEMA in various solvents.
The absorption maximum wave numbers in the α band of H and vitamin B 12 derivatives are shown. FIG. 9 shows the correlation between the absorption maximum wave number in the α band of B 12 -HPEMA / PHEMA-H and vitamin B 12 derivatives and the polarity parameter E T N of the solvent.
実施例１１
＜Ｂ12‐ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ（修飾率２０．２％）のアコシアノ化＞
得られた化合物のＵＶ−ｖｉｓスペクトルを図１０に示す。
Example 11
<Akoshiano of B 12 -HPEMA / PHEMA-H (modification ratio 20.2%)>
The UV-vis spectrum of the obtained compound is shown in FIG.
実施例１２
＜Ｂ12‐ＨＢＰ（ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ）のＣｏ（ＩＩ）化＞
が黒緑色から橙色に変化するまで６０％過塩素酸水溶液をゆっくりと滴下した。塩化メチレン１００ｍＬを加え、蒸留水で３回洗浄した。無水硫酸ナトリウムで脱水後、溶媒を減圧留去してクロロホルム／ｎ−ヘキサンで再沈殿し、橙色粉末を得た。
収量 ２２．０ｍｇ
得られた化合物のＵＶ−ｖｉｓスペクトルを図１１に示す。
Example 12
<Co (II) conversion of B 12 -HBP (HPEMA / PHEMA-H)>
Yield 22.0mg
The UV-vis spectrum of the obtained compound is shown in FIG.
実施例１３
＜Ｂ12‐ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ（Ｃｏ（ＩＩ）体）のＣＶ測定＞
実施例１２で合成したＢ12‐ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ（Ｃｏ（ＩＩ）体）（
修飾率１５．８％）を用いて、修飾されたビタミンＢ12誘導体０．５ｍＭ、過塩素酸テトラ−ｎ−ブチルアンモニウム０．１ＭのＤＭＦ溶液を調整した。内部標準として少量のフェロセンを加え、作用電極にグラッシカーボン電極、対電極に白金電極、参照電極にＡｇ／ＡｇＣｌ電極を用いサイクリックボルタンメトリー（ＣＶ）測定を行った（図１２）。次いで、臭化フェネチル２０μＬを加えて同様にＣＶ測定を行った（図１３）。
Example 13
<CV measurement of B 12 -HPEMA / PHEMA-H ( Co (II) form)>
B 12 -HPEMA / PHEMA-H (Co (II) form) synthesized in Example 12 (
The modified vitamin B 12 derivative 0.5 mM and tetra-n-butylammonium perchlorate 0.1 M in DMF were prepared using a modification rate of 15.8%. A small amount of ferrocene was added as an internal standard, and cyclic voltammetry (CV) measurement was performed using a glassy carbon electrode as a working electrode, a platinum electrode as a counter electrode, and an Ag / AgCl electrode as a reference electrode (FIG. 12). Subsequently, 20 μL of phenethyl bromide was added and CV measurement was performed in the same manner (FIG. 13).
実施例１４
＜ビタミンＢ12誘導体（Ｃｏ（ＩＩ）体）＞
ビタミンＢ12誘導体（Ｃｏｂ（ＩＩ）６Ｃ1エステル）を用いて、ビタミンＢ12誘導体０
．５ｍＭ、過塩素酸テトラ−ｎ−ブチルアンモニウム０．１ＭのＤＭＦ溶液を調整した。内部標準として少量のフェロセンを加え、作用電極にグラッシカーボン電極、対電極に白金電極、参照電極にＡｇ／ＡｇＣｌ電極を用いＣＶ測定を行った（図１４）。次いで、臭化フェネチル２０μＬを加えてＣＶ測定を行った（図１５）。
Example 14
<Vitamin B 12 derivative (Co (II) form)>
Using vitamin B 12 derivative (Cob (II) 6C 1 ester), vitamin B 12 derivative 0
. A 5 mM DMF solution of tetra-n-butylammonium perchlorate 0.1 M was prepared. A small amount of ferrocene was added as an internal standard, and CV measurement was performed using a glassy carbon electrode as a working electrode, a platinum electrode as a counter electrode, and an Ag / AgCl electrode as a reference electrode (FIG. 14). Next, 20 μL of phenethyl bromide was added to perform CV measurement (FIG. 15).
実施例１５
＜Ｂ12−ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈを用いた臭化フェネチルの脱ブロモ化反応＞
実施例４で合成したＢ12‐ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ（修飾率７．２％）を用いて、修飾されているビタミンＢ12誘導体が２．０×１０-5Ｍ、臭化フェネチルが１．９×１０-3Ｍに調整されたメタノール溶液２５ｍＬに酸化チタン１９ｍｇを加え、１５分間窒素バブリングして脱気した。それから、撹拌しながらブラックライト（フナコシ（株）製、１５Ｗ）により反応器外表面における紫外線強度１．７６ｍＷｃｍ-2で紫外線を１４時間照射し、ＧＣ−ＭＳで生成物解析及び定量を行った。同様の操作を実施例４、６及び９で合
成したＢ12‐ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈ（修飾率１．９％、６．６％、１５．６％）でも行った。反応結果を下記の表３に示した。
Example 15
<Debrominated of phenethyl bromide reaction with B 12 -HPEMA / PHEMA-H>
Using B 12 -HPEMA / PHEMA-H (modification rate: 7.2%) synthesized in Example 4, the modified vitamin B 12 derivative was 2.0 × 10 −5 M and phenethyl bromide was 1. 19 mg of titanium oxide was added to 25 mL of a methanol solution adjusted to 9 × 10 −3 M, and deaerated by bubbling nitrogen for 15 minutes. Then, ultraviolet light was irradiated for 14 hours with a UV light intensity of 1.76 mWcm −2 on the outer surface of the reactor with black light (15 W manufactured by Funakoshi Co., Ltd.) while stirring, and product analysis and quantification were performed by GC-MS. The same operation was performed for B 12 -HPEMA / PHEMA-H synthesized in Examples 4, 6, and 9 (modification rates: 1.9%, 6.6%, 15.6%). The reaction results are shown in Table 3 below.
実施例１６
＜ビタミンＢ12誘導体を用いた臭化フェネチルの脱ブロモ化反応＞
ビタミンＢ12誘導体（Ｃｏｂ（ＩＩ）６Ｃ1エステル）が２．０×１０-5Ｍ、臭化フェ
ネチルが１．９×１０-3Ｍに調整されたメタノール溶液２５ｍＬに酸化チタン１９ｍｇを加え、１５分間窒素バブリングして脱気した。それから、撹拌しながらブラックライト（フナコシ（株）製、１５Ｗ）により反応器外表面における紫外線強度１．７６ｍＷｃｍ-2で紫外線を１４時間照射し、ＧＣ−ＭＳで生成物解析及び定量を行った。反応結果を下記の表３に示した。
Example 16
<Debromination of phenethyl bromide using vitamin B 12 derivative>
19 mg of titanium oxide was added to 25 mL of a methanol solution adjusted to 2.0 × 10 −5 M of vitamin B 12 derivative (Cob (II) 6C 1 ester) and 1.9 × 10 −3 M of phenethyl bromide, Degas by nitrogen bubbling for a minute. Then, ultraviolet light was irradiated for 14 hours with a UV light intensity of 1.76 mWcm −2 on the outer surface of the reactor with black light (15 W manufactured by Funakoshi Co., Ltd.) while stirring, and product analysis and quantification were performed by GC-MS. The reaction results are shown in Table 3 below.
実施例１７
＜ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈを用いた臭化フェネチルの脱ブロモ化反応＞
臭化フェネチルが１．９×１０-3Ｍに調整されたメタノール溶液２５ｍＬに酸化チタン１９ｍｇ、ＨＰＥＭＡ／ＰＨＥＭＡ０．４４ｍｇを加え、１５分間窒素バブリングして脱気した。それから、撹拌しながらブラックライト（フナコシ（株）製、１５Ｗ）により反応器外表面における紫外線強度１．７６ｍＷｃｍ-2で紫外線を１４時間照射し、ＧＣ−ＭＳで生成物解析及び定量を行った。反応結果を表３に示した。
Example 17
<Debromination of phenethyl bromide using HPEMA / PHEMA-H>
Titanium oxide 19 mg and HPEMA / PHEMA 0.44 mg were added to 25 mL of a methanol solution adjusted to 1.9 × 10 −3 M of phenethyl bromide, and deaerated by bubbling nitrogen for 15 minutes. Then, ultraviolet light was irradiated for 14 hours with a UV light intensity of 1.76 mWcm −2 on the outer surface of the reactor with black light (15 W manufactured by Funakoshi Co., Ltd.) while stirring, and product analysis and quantification were performed by GC-MS. The reaction results are shown in Table 3.
実施例１８
＜ビタミンＢ12誘導体＋ＨＰＥＭＡ／ＰＨＥＭＡ−Ｈを用いた臭化フェネチルの脱ブロモ化反応＞
ビタミンＢ12誘導体（Ｃｏｂ（ＩＩ）６Ｃ1エステル）が２．０×１０-5Ｍ、臭化フェネ
チルが１．９×１０-3Ｍに調整されたメタノール溶液２５ｍＬに酸化チタン１９ｍｇ、ＨＰＥＭＡ／ＰＨＥＭＡ５．０４ｍｇを加え、１５分間窒素バブリングして脱気した。それから、撹拌しながらブラックライト（フナコシ（株）製、１５Ｗ）により反応器外表面における紫外線強度１．７６ｍＷｃｍ-2で紫外線を１４時間照射し、ＧＣ−ＭＳで生成物解析及び定量を行った。反応結果を表３に示した。
<Debrominated reaction of phenethyl bromide using the vitamin B 12 derivative + HPEMA / PHEMA-H>
Vitamin B 12 derivative (Cob (II) 6C 1 ester) was adjusted to 2.0 × 10 −5 M and phenethyl bromide was adjusted to 1.9 × 10 −3 M in 25 mL of methanol solution, 19 mg of titanium oxide, HPEMA / PHEMA5 0.04 mg was added and degassed by nitrogen bubbling for 15 minutes. Then, ultraviolet light was irradiated for 14 hours with a UV light intensity of 1.76 mWcm −2 on the outer surface of the reactor with black light (15 W manufactured by Funakoshi Co., Ltd.) while stirring, and product analysis and quantification were performed by GC-MS. The reaction results are shown in Table 3.
実施例１９
＜コアシェル型ＨＢＰ（ＨＰＳ／ＰＨＥＭＡ−Ｈ）へのビタミンＢ12誘導体の化学修飾＞
２５ｍＬ二口ナス型フラスコにビタミンＢ12誘導体（（ＣＮ）2Ｃｏｂ（ＩＩＩ）６Ｃ1エステル）６５．４ｍｇ（６．０８×１０-5ｍｏｌ）、参考例４で合成したＨＰＳ／ＰＨＥＭＡ−Ｈ４０．６ｍｇ（含ＯＨ基３．０９×１０-4ｍｏｌ）、ＤＭＡＰ３７．５ｍｇ（３．０７×１０-4ｍｏｌ）を入れ、窒素置換した。乾燥ＤＭＦ溶液（３ｍＬ）を加え溶解させた後、氷浴下でＥＤＣ／ＨＣｌ５８．７ｍｇ（３．０６×１０-4ｍｏｌ）を加え、室温で４時間撹拌した。その後、クロロホルム１００ｍＬを加え蒸留水で３回洗浄した。無水硫酸ナトリウムで脱水後、溶媒を濃縮し、ＧＰＣ（溶離液クロロホルム、検出器波長３７１ｎｍ）により精製した。分取した第一成分（ブロード）にＫＣＮ水溶液（ＫＣＮ８６．４ｍｇ（１．３３×１０-3 ｍｏｌ）、水１００ｍＬ）を加え分液漏斗で激しく振とうし、蒸留水で３回洗浄した。無水硫酸ナトリウムで脱水後、溶媒を減圧留去してクロロホルム／ｎ−ヘキサンで再沈殿した。生成物をろ過、減圧乾燥し紫色粉末を得た。
収量 ５３．７ｍｇ 修飾率 １３．２％
Ｂ12‐ＨＰＳ／ＰＨＥＭＡ−Ｈ １ｇ当りの固定化量 ５１９ｍｇ
Example 19
<Chemical modification of vitamin B 12 derivatives of the core-shell HBP (HPS / PHEMA-H) >
Yield 53.7 mg Modification rate 13.2%
Immobilization amount per gram of B 12 -HPS / PHEMA-H 519 mg
実施例２０
＜コアシェル型ＨＢＰ（ＨＰＳ／ＰＨＥＭＡ−Ｈ）へのビタミンＢ12誘導体の化学修飾＞ビタミンＢ12誘導体の仕込み量：０．４当量
ビタミンＢ12誘導体９８．０ｍｇ（９．１２×１０-5ｍｏｌ）、ＨＰＳ／ＰＨＥＭＡ−Ｈ３０．７ｍｇ（含ＯＨ基２．３４×１０-4ｍｏｌ）、ＥＤＣ／ＨＣｌ４８．１ｍｇ（２．５１×１０-4ｍｏｌ）、ＤＭＡＰ２８．６ｍｇ（２．３４×１０-4ｍｏｌ）を用いて実施例１９と同様の操作を行った。
収量 ４８．４ｍｇ 修飾率 １６．８％
Ｂ12‐ＨＰＳ／ＰＨＥＭＡ−Ｈ １ｇ当りの固定化量 ５７８ｍｇ
ＧＰＣチャートを図１６に示す。ビタミンＢ12誘導体修飾後のＵＶ−ｖｉｓスペクトルを図１７に、1Ｈ−ＮＭＲスペクトルを図１８に示す。
Example 20
<Core-shell HBP (HPS / PHEMA-H) vitamin B 12 derivatives chemically modified to> Vitamin B 12 charge of derivatives: 0.4 eq vitamin B 12 derivative 98.0mg (9.12 × 10 -5 mol) , HPS / PHEMA-H 30.7 mg (OH-containing group 2.34 × 10 −4 mol), EDC / HCl 48.1 mg (2.51 × 10 −4 mol), DMAP 28.6 mg (2.34 × 10 −4 mol) ), And the same operation as in Example 19 was performed.
Yield 48.4 mg Modification rate 16.8%
Immobilization amount per 1 g of B 12 -HPS / PHEMA-H 578 mg
A GPC chart is shown in FIG. FIG. 17 shows the UV-vis spectrum after modification with the vitamin B 12 derivative, and FIG. 18 shows the 1 H-NMR spectrum.
実施例２１
＜Ｂ12‐ＨＰＳ／ＰＨＥＭＡ−Ｈのアコシアノ化＞
実施例２０で合成したＢ12‐ＨＰＳ／ＰＨＥＭＡ−Ｈ（修飾率１６．８％）２７．９ｍｇを塩化メチレン５０ｍＬに溶解し、３０％過塩素酸水溶液４０ｍＬを加え、分液漏斗で激しく振とうした。有機相が紫色から赤色に変化した後、蒸留水で３回洗浄した。無水硫酸ナトリウムで脱水後、溶媒を減圧留去して乾固した。
Example 21
<Akoshiano of B 12 -HPS / PHEMA-H>
27.9 mg of B 12 -HPS / PHEMA-H (modification rate 16.8%) synthesized in Example 20 was dissolved in 50 mL of methylene chloride, 40 mL of 30% aqueous perchloric acid solution was added, and the mixture was vigorously shaken with a separatory funnel. did. After the organic phase changed from purple to red, it was washed 3 times with distilled water. After dehydration with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to dryness.
実施例２２
＜Ｂ12‐ＨＰＳ／ＰＨＥＭＡ−ＨのＣｏ（ＩＩ）化＞
実施例２１で生成したＢ12‐ＨＰＳ／ＰＨＥＭＡ−Ｈ（アコシアノ体）をアセトニトリル−メタノール（１：１（ｖ／ｖ））混合溶媒６０ｍＬに溶解し、１０分間撹拌しながら窒素バブリングして脱気した。そのまま溶液が赤色から黒緑色に変化するまでＮａＢＨ4
を加えた後、５分間窒素バブリングした。その後、溶液が黒緑色から橙色に変化するまで６０％過塩素酸水溶液をゆっくりと滴下した。塩化メチレン１００ｍＬを加え、蒸留水で３回洗浄した。無水硫酸ナトリウムで脱水後、溶媒を減圧留去してクロロホルム／ｎ−ヘキサンで再沈殿し、橙色粉末を得た。
収量 １８．０ｍｇ
Ｂ12−ＨＰＳ／ＰＨＥＭＡ（Ｃｏ（ＩＩ）体）のＵＶ−ｖｉｓスペクトル（溶媒：塩化メチレン）を図１９に示す。
Example 22
<Co (II) conversion of B 12 -HPS / PHEMA-H>
B 12 -HPS / PHEMA-H (acocyano compound) produced in Example 21 was dissolved in 60 mL of a mixed solvent of acetonitrile-methanol (1: 1 (v / v)) and deaerated by nitrogen bubbling while stirring for 10 minutes. did. NaBH 4 until the solution turns from red to black-green
Then, nitrogen was bubbled for 5 minutes. Thereafter, a 60% aqueous perchloric acid solution was slowly added dropwise until the solution changed from black-green to orange. 100 mL of methylene chloride was added and washed 3 times with distilled water. After dehydration with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure and reprecipitated with chloroform / n-hexane to obtain an orange powder.
Yield 18.0mg
FIG. 19 shows the UV-vis spectrum (solvent: methylene chloride) of B 12 -HPS / PHEMA (Co (II) form).
実施例２３
＜Ｂ12‐ＨＰＳ／ＰＨＥＭＡ−Ｈ臭化フェネチルの脱ブロモ化反応＞
実施例２０で合成したＢ12−ＨＰＳ／ＰＨＥＭＡ−Ｈ（修飾率１６．８％）を用いて、修飾されているビタミンＢ12誘導体が２．０×１０-5Ｍ、臭化フェネチルが１．９×１０-3Ｍに調整されたメタノール溶液２５ｍＬに酸化チタン１９ｍｇを加え、１５分間窒素バブリングして脱気した。それから、撹拌しながらブラックライト（フナコシ（株）製、１５Ｗ）により反応器外表面における紫外線強度１．７６ｍＷｃｍ-2で紫外線を１４時間照射し、ＧＣ−ＭＳで生成物解析及び定量を行った。
<Debromination reaction of B 12 -HPS / PHEMA-H phenethyl bromide>
Using B 12 -HPS / PHEMA-H (modification rate 16.8%) synthesized in Example 20, the modified vitamin B 12 derivative was 2.0 × 10 −5 M, and phenethyl bromide was 1. 19 mg of titanium oxide was added to 25 mL of a methanol solution adjusted to 9 × 10 −3 M, and deaerated by bubbling nitrogen for 15 minutes. Then, ultraviolet light was irradiated for 14 hours with a UV light intensity of 1.76 mWcm −2 on the outer surface of the reactor with black light (15 W manufactured by Funakoshi Co., Ltd.) while stirring, and product analysis and quantification were performed by GC-MS.
実施例２４
＜Ｂ12‐ＨＰＥＭＡ／ＰＨＥＭＡ−ＨのＳＥＭ測定＞
実施例７で合成したＢ12−ＨＰＥＭＡ／ＰＨＥＭＡ（修飾率２０．２％）をメタノール−ベンゼン混合溶液（１：１，ｖ／ｖ）に溶解し、スライドガラス（松波ガラス製）上にスピンコーティング法でキャストした。２４時間減圧乾燥した後、走査型電子顕微鏡（ＳＥＭ）を用いて測定したＳＥＭ画像を図２１に示す。
Example 24
<SEM measurement of B 12 -HPEMA / PHEMA-H>
B 12 -HPEMA / PHEMA synthesized in Example 7 (modification rate 20.2%) was dissolved in a methanol-benzene mixed solution (1: 1, v / v) and spin-coated on a slide glass (manufactured by Matsunami Glass). Cast by law. FIG. 21 shows an SEM image measured using a scanning electron microscope (SEM) after drying under reduced pressure for 24 hours.
実施例２５
実施例１
＜ジチオカルバメート基を分子末端に有する直鎖状ポリ（メタクリル酸メチル）をシェル鎖に有するコア（共重合系）−シェル型ハイパーブランチポリマー（ＨＰＥＭＡ−ＨＥＭＡ／ＰＭＭＡ）の合成＞
３００ｍＬ反応フラスコに参考例８で得られたアクリル系共重合型ハイパーブランチポリマー１．５７ｇ、メタクリル酸メチル４０．０５ｇ、テトラエチルチウラムジスルフィド１．１９ｇ、及びＤＭＦ１６６．５ｇを仕込み、撹拌して淡黄色透明溶液を調製した後、反応系内を窒素置換した。この溶液の真ん中から１００Ｗの高圧水銀灯［セン特殊光源（株）製、ＨＬ−１００］を点灯させ、内部照射による光重合反応を、撹拌下で、室温で１３時間行った。つぎにこの反応液をＴＨＦ９３５ｇ−ヘキサン３００ｇの混合溶液に添加してポリマーを粘稠物状態とした。得られた粘稠物をデカンテーションにより分別し、
４０℃温浴下テトラヒドロフラン１００ｇに再溶解した後、この溶液をジイソプロピルエーテル７２０ｇに添加してポリマーをスラリー状態で再沈した。このスラリーを濾過し、真空乾燥して、白色粉末の目的物１０．０ｇを得た。得られたポリマーのゲル浸透クロマトグラフィーによるポリスチレン換算で測定された重量平均分子量Ｍｗは７１，０００であり、分散度Ｍｗ／Ｍｎは８．２３であった。
得られたハイパーブランチポリマーは、下記の化学式（１０７）で表される構造式を重合開始部位、化学式（１０８）で表される直鎖構造の繰り返し単位と化学式（１０９）で表される枝分かれ構造の繰り返し単位とからなる重合鎖部分を有し、そして該重合鎖部分の重合終了部位に化学式（１１０）で表される直鎖状の繰り返し構造結合してなるハイパーブランチポリマーである。
Example 1
<Synthesis of a core (copolymerization type) -shell hyperbranched polymer (HPEMA-HEMA / PMMA) having a linear poly (methyl methacrylate) having a dithiocarbamate group at a molecular end in a shell chain>
A 300 mL reaction flask was charged with 1.57 g of the acrylic copolymer hyperbranched polymer obtained in Reference Example 8, 40.05 g of methyl methacrylate, 1.19 g of tetraethylthiuram disulfide, and 166.5 g of DMF and stirred to obtain a pale yellow transparent After preparing the solution, the inside of the reaction system was purged with nitrogen. A 100 W high-pressure mercury lamp (manufactured by Sen Special Light Source Co., Ltd., HL-100) was turned on from the middle of this solution, and a photopolymerization reaction by internal irradiation was performed at room temperature for 13 hours under stirring. Next, this reaction solution was added to a mixed solution of THF 935 g-hexane 300 g to make the polymer in a viscous state. The resulting viscous material is separated by decantation,
After redissolving in 100 g of tetrahydrofuran in a 40 ° C. warm bath, this solution was added to 720 g of diisopropyl ether to reprecipitate the polymer in a slurry state. This slurry was filtered and vacuum-dried to obtain 10.0 g of the desired product as a white powder. The weight average molecular weight Mw measured by gel permeation chromatography of the obtained polymer in terms of polystyrene was 71,000, and the dispersity Mw / Mn was 8.23.
The obtained hyperbranched polymer has a structural formula represented by the following chemical formula (107) as a polymerization initiation site, a repeating unit having a linear structure represented by the chemical formula (108), and a branched structure represented by the chemical formula (109). A hyperbranched polymer having a linear chain structure represented by the chemical formula (110) at the polymerization end portion of the polymer chain portion.
実施例２６
＜分子末端が還元されたジチオカルバメート基を分子末端に有する直鎖状ポリ（メタクリル酸メチル）をシェル鎖に有するコア（アクリル系共重合）−シェル型ハイパーブランチポリマー（ＨＰＥＭＡ−ＨＥＭＡ／ＰＭＭＡ−Ｈ）の合成＞
３００ｍＬガラス製反応フラスコに、実施例２５で得たジチオカルバメート基を分子末端に有するコア（アクリル系共重合）−シェル型ハイパーブランチポリマー（ＨＰＥＭＡ−ＨＥＭＡ／ＰＭＭＡ、Ｍｗ：７１，０００、Ｍｗ／Ｍｎ：８．２３）４．０ｇ、テトラヒドロフラン７６．０ｇを仕込み、撹拌してうす黄色透明溶液を調製した後、水素化トリブチルスズ［アルドリッチ社製］４．１ｍＬを添加した。反応系内を窒素置換し、この溶液の真ん中から１００Ｗの高圧水銀灯［セン特殊光源（株）製、ＨＬ−１００］を点灯させ、内部照射による光反応を、撹拌下、室温で３.５時間行った。次に、この反応溶液を
ヘキサン１Ｌに添加して、ハイパーブランチポリマーをスラリー状態で再沈した。この再沈を３回繰り返した後、得られたスラリーを濾過し、真空乾燥して、白色粉末のジチオカルバメート基が水素に置換されたハイパーブランチポリマー２．５ｇを得た。ゲル浸透クロマトグラフィーによるポリスチレン換算で測定される重量平均分子量Ｍｗは３４，０００、分散度Ｍｗ／Ｍｎは４．６８であった。１Ｈ−ＮＭＲスペクトルを図２２に示す。得られたハイパーブランチポリマーをＤＭＦへ溶解させ、３０８μｇ／ｍＬとなるように調整した溶液の紫外可視吸収スペクトル測定を行った。還元反応前に観測されたジチオカルバメート基に由来する２８０ｎｍを中心とするピークが、還元反応後減少（還元前と比較してジチオカルバメート基８９．３％減少）しているのが観測された。これより得られたハイパーブランチポリマーは、上記の化学式（１０７）で表される構造式を重合開始部位、化学式（１０８）で表される直鎖構造の繰り返し単位と化学式（１０８）で表される枝分かれ構造の繰り返し単位とからなる重合鎖部分を有し、そして該重合鎖部分の重合終了部位に化学式（１０９）で表される直鎖状の繰り返し構造を有するハイパーブランチポリマーのジチオカルバメート基が９０％近く還元されて水素になったハイパーブランチポリマーである。
Example 26
<Core (acrylic copolymer) -shell type hyperbranched polymer (HPEMA-HEMA / PMMA-H) having a linear poly (methyl methacrylate) having a dithiocarbamate group reduced at the molecular end at the molecular end in the shell chain Synthesis)
In a 300 mL glass reaction flask, a core (acrylic copolymer) -shell hyperbranched polymer (HPEMA-HEMA / PMMA, Mw: 71,000, Mw / Mn) having the dithiocarbamate group obtained in Example 25 at the molecular end. : 8.23) 4.0 g of tetrahydrofuran and 76.0 g of tetrahydrofuran were charged, and after stirring to prepare a light yellow transparent solution, 4.1 mL of tributyltin hydride [manufactured by Aldrich] was added. The reaction system was purged with nitrogen, and a 100 W high-pressure mercury lamp (manufactured by Sen Special Light Source Co., Ltd., HL-100) was turned on from the middle of this solution. went. Next, this reaction solution was added to 1 L of hexane to reprecipitate the hyperbranched polymer in a slurry state. After repeating this reprecipitation three times, the resulting slurry was filtered and vacuum dried to obtain 2.5 g of a hyperbranched polymer in which the dithiocarbamate group of the white powder was replaced with hydrogen. The weight average molecular weight Mw measured by gel permeation chromatography in terms of polystyrene was 34,000, and the degree of dispersion Mw / Mn was 4.68. The 1H-NMR spectrum is shown in FIG. The obtained hyperbranched polymer was dissolved in DMF, and an ultraviolet-visible absorption spectrum measurement of a solution adjusted to 308 μg / mL was performed. It was observed that the peak centered at 280 nm derived from the dithiocarbamate group observed before the reduction reaction decreased after the reduction reaction (89.3% decrease in dithiocarbamate groups compared to before the reduction reaction). The hyperbranched polymer thus obtained is represented by the chemical formula (108), the structural formula represented by the above chemical formula (107), the polymerization initiation site, the linear repeating unit represented by the chemical formula (108), and the chemical formula (108). The hyperbranched polymer having a linear repeating structure represented by the chemical formula (109) has a polymer chain portion composed of a repeating unit having a branched structure, and 90 parts of the polymer chain portion has a polymerization end portion. It is a hyperbranched polymer that has been reduced to nearly hydrogen to hydrogen.
実施例２７
＜ジチオカルバメート基を分子末端に有する直鎖状ポリ（メタクリル酸tert-ブチル）を
シェル鎖に有するコア（共重合系）−シェル型ハイパーブランチポリマー（ＨＰＳ−ＨＥＭＡ／ＰＢＭＡ）の合成＞
３００ｍＬ反応フラスコに参考例９で得られ共重合ハイパーブランチポリマー（ＨＰＳ−ＨＥＭＡ）２．００ｇ、メタクリル酸tert-ブチル（ＢＭＡ）２５．１８ｇ、テトラエ
チルチウラムジスルフィド１．５０ｇ、及びＤＭＦ１０８．７ｇを仕込み、撹拌して淡黄色透明溶液を調製した後、反応系内を窒素置換した。この溶液の真ん中から１００Ｗの高
圧水銀灯［セン特殊光源（株）製、ＨＬ−１００］を点灯させ、内部照射による光重合反応を、撹拌下で、室温で７時間行った。つぎにこの反応液をヘキサン５００ｇに添加してポリマーを粘稠物状態とした。得られた粘稠物をデカンテーションにより分別し、４０℃温浴下テトラヒドロフラン１３０ｇに再溶解した後、この溶液をヘキサン７５０ｇに添加してポリマーをスラリー状態で再沈した。このスラリーを濾過し、真空乾燥して、白色粉末の目的物１３ｇを得た。得られたポリマーのゲル浸透クロマトグラフィーによるポリスチレン換算で測定された重量平均分子量Ｍｗは２１１,０００であり、分散度Ｍｗ／Ｍｎ
は４．２７であった。得られたハイパーブランチポリマーをＤＭＦへ溶解させ、１０５μｇ／ｍＬとなるように調整した溶液の紫外可視吸収スペクトル測定を行った。ジチオカルバメート基に由来する２８０ｎｍ中心とするピークの吸収スペクトルからＳ−ＤＣの２８０ｎｍにおける吸光度の検量線を用いて、Ｓ−ＤＣ量を定量したところ、本ポリマーの組成比は、Ｓ−ＤＣ：ＨＥＭＡ：ＢＭＡ＝１．０：１．１：３１．８（ｍｏｌ比）であった。また1Ｈ−ＮＭＲ測定より、ＢＭＡのブチル基がブロードに観測され、シェルの形成が
確認された（図２３）。得られたハイパーブランチポリマーは、下記の化学式（１１１）で表される構造式を重合開始部位、化学式（１１２）で表される直鎖構造の繰り返し単位と化学式（１１３）で表される枝分かれ構造の繰り返し単位とからなる重合鎖部分を有し、そして該重合鎖部分の重合終了部位に化学式（１１４）で表される直鎖状の繰り返し構造を結合してなるハイパーブランチポリマーである。
<Synthesis of core (copolymerization system) -shell hyperbranched polymer (HPS-HEMA / PBMA) having a linear poly (tert-butyl methacrylate) having a dithiocarbamate group at the molecular terminal in the shell chain>
A 300 mL reaction flask was charged with 2.00 g of the copolymer hyperbranched polymer (HPS-HEMA) obtained in Reference Example 9, 25.18 g of tert-butyl methacrylate (BMA), 1.50 g of tetraethylthiuram disulfide, and 108.7 g of DMF, After stirring to prepare a pale yellow transparent solution, the reaction system was purged with nitrogen. A 100 W high-pressure mercury lamp (manufactured by Sen Special Light Source Co., Ltd., HL-100) was turned on from the middle of this solution, and a photopolymerization reaction by internal irradiation was performed at room temperature for 7 hours under stirring. Next, this reaction solution was added to 500 g of hexane to make the polymer into a viscous state. The resulting viscous material was separated by decantation and redissolved in 130 g of tetrahydrofuran in a 40 ° C. warm bath, and then this solution was added to 750 g of hexane to reprecipitate the polymer in a slurry state. This slurry was filtered and vacuum-dried to obtain 13 g of the desired product as a white powder. The weight average molecular weight Mw measured in terms of polystyrene by gel permeation chromatography of the obtained polymer was 211,000, and the degree of dispersion Mw / Mn
Was 4.27. The obtained hyperbranched polymer was dissolved in DMF, and an ultraviolet-visible absorption spectrum measurement of a solution adjusted to be 105 μg / mL was performed. The amount of S-DC was quantified from the absorption spectrum of the peak centered at 280 nm derived from the dithiocarbamate group using the calibration curve of the absorbance at 280 nm of S-DC. : BMA = 1.0: 1.1: 31.8 (mol ratio). From 1 H-NMR measurement, the butyl group of BMA was observed broadly, confirming the formation of a shell (FIG. 23). The obtained hyperbranched polymer has a structural formula represented by the following chemical formula (111) as a polymerization initiation site, a linear repeating unit represented by the chemical formula (112), and a branched structure represented by the chemical formula (113). A hyperbranched polymer having a polymer chain portion composed of the following repeating unit, and a linear repeating structure represented by the chemical formula (114) bonded to the polymerization end portion of the polymer chain portion.
実施例２８
＜分子末端が還元されたジチオカルバメート基を分子末端に有する直鎖状ポリ（メタクリル酸メチル）をシェル鎖に有するコア（共重合）−シェル型ハイパーブランチポリマー（ＨＰＳ−ＨＥＭＡ／ＰＢＭＡ−Ｈ）の合成＞
３００ｍＬガラス製反応フラスコに、実施例２７で得たジチオカルバメート基を分子末端に有するコア（共重合）−シェル型ハイパーブランチポリマー（ＨＰＳ−ＨＥＭＡ／ＢＭＡ、Ｍｗ：２１１，０００、Ｍｗ／Ｍｎ：４．２７）４．０ｇ、テトラヒドロフラン７６．０ｇを仕込み、撹拌してうす黄色透明溶液を調製した後、水素化トリブチルスズ［アルドリッチ社製］２．４ｍＬを添加した。反応系内を窒素置換し、この溶液の真ん中から１００Ｗの高圧水銀灯［セン特殊光源（株）製、ＨＬ−１００］を点灯させ、内部照射による光反応を、撹拌下、室温で３.５時間行った。次に、この反応溶液をヘキサン１Ｌに
添加して、ハイパーブランチポリマーをスラリー状態で再沈した。この再沈を３回繰り返した後、得られたスラリーを濾過し、真空乾燥して、白色粉末のジチオカルバメート基が水素に置換されたハイパーブランチポリマー２．６ｇを得た。ゲル浸透クロマトグラフィーによるポリスチレン換算で測定される重量平均分子量Ｍｗは１６３，０００、分散度Ｍｗ／Ｍｎは２．６３であった。1Ｈ−ＮＭＲスペクトルを図２４に示す。得られたハイパ
ーブランチポリマーをＤＭＦへ溶解させ、１０００μｇ／ｍＬとなるように調整した溶液の紫外可視吸収スペクトル測定を行った。還元反応前に観測されたジチオカルバメート基に由来する２８０ｎｍを中心とするピークが、還元反応後減少（還元前と比較してジチオカルバメート基９３．０％減少）しているのが観測された。これより得られたハイパーブランチポリマーは、上記の化学式（１１１）で表される構造式を重合開始部位とし、化学式（１１２）で表される直鎖構造の繰り返し単位と化学式（１１３）で表される枝分かれ
構造の繰り返し単位とからなる重合鎖部分を有し、そして該重合鎖部分の重合終了部位に化学式（１１４）で表される直鎖状の繰り返し構造を結合してなるハイパーブランチポリマーのジチオカルバメート基が９０％以上還元されて水素になったハイパーブランチポリマーである。
Example 28
<Core (copolymerization) -shell hyperbranched polymer (HPS-HEMA / PBMA-H) having a linear poly (methyl methacrylate) having a dithiocarbamate group reduced at the molecular end at the molecular end in the shell chain Synthesis>
In a 300 mL glass reaction flask, a core (copolymerization) -shell hyperbranched polymer (HPS-HEMA / BMA, Mw: 211,000, Mw / Mn: 4) having the dithiocarbamate group obtained in Example 27 at the molecular end. .27) 4.0 g of tetrahydrofuran and 76.0 g of tetrahydrofuran were charged, and after stirring to prepare a light yellow transparent solution, 2.4 mL of tributyltin hydride [manufactured by Aldrich] was added. The reaction system was purged with nitrogen, and a 100 W high-pressure mercury lamp (manufactured by Sen Special Light Source Co., Ltd., HL-100) was turned on from the middle of this solution. went. Next, this reaction solution was added to 1 L of hexane to reprecipitate the hyperbranched polymer in a slurry state. After repeating this reprecipitation three times, the resulting slurry was filtered and dried under vacuum to obtain 2.6 g of a hyperbranched polymer in which the dithiocarbamate group of the white powder was replaced with hydrogen. The weight average molecular weight Mw measured by gel permeation chromatography in terms of polystyrene was 163,000, and the degree of dispersion Mw / Mn was 2.63. The 1 H-NMR spectrum is shown in FIG. The obtained hyperbranched polymer was dissolved in DMF, and ultraviolet-visible absorption spectrum measurement of a solution adjusted to 1000 μg / mL was performed. It was observed that the peak around 280 nm derived from the dithiocarbamate group observed before the reduction reaction decreased after the reduction reaction (dithiocarbamate group decreased by 93.0% compared to before the reduction). The hyperbranched polymer thus obtained is represented by the chemical formula (113) and the repeating unit having a linear structure represented by the chemical formula (112) with the structural formula represented by the chemical formula (111) as a polymerization initiation site. A dithiophene of a hyperbranched polymer having a polymer chain portion composed of a repeating unit having a branched structure and having a linear repeating structure represented by the chemical formula (114) bonded to the polymerization end portion of the polymer chain portion. It is a hyperbranched polymer in which carbamate groups are reduced to 90% or more to form hydrogen.
実施例２９
＜コアシェル型ＨＢＰ（ＨＰＥＭＡ−ＨＥＭＡ／ＰＭＭＡ）へのビタミンＢ12誘導体の化学修飾＞
収量 ２４ｍｇ ビタミンＢ12誘導体の修飾率 ９．２％
Example 29
<Chemical modification of vitamin B 12 derivatives of the core-shell HBP (HPEMA-HEMA / PMMA) >
Yield 24 mg Vitamin B 12 derivative modification rate 9.2%
実施例３０
＜コアシェル型ＨＢＰ（ＨＰＳ−ＨＥＭＡ／ＰＢＭＡ）へのビタミンＢ12誘導体の化学修飾＞
ｏｌ）、コアシェル型ＨＢＰとしてＨＰＳ−ＨＥＭＡ／ＰＢＭＡ１０１．４ｍｇ（含ＯＨ基２．１２×１０-5ｍｏｌ）、ジメチルアミノピリジン（ＤＭＡＰ）１３．０ｍｇ（１．０６×１０-4ｍｏｌ）を入れ、窒素置換した。乾燥Ｎ，Ｎ−ジメチルホルムアミド（ＤＭＦ）溶液（３ｍＬ）を加え溶解させた後、氷浴下で１−エチル−３−（３−ジメチルアミノプロピル）カルボジイミド塩酸塩（ＥＤＣ／ＨＣｌ）２３．１ｍｇ（１．２１×１０-4ｍｏｌ）を加え、室温で４時間撹拌した。その後、クロロホルム１００ｍＬを加え蒸留水で３回洗浄した。無水硫酸ナトリウムで脱水後、溶液を濃縮し、ＧＰＣ（溶離液クロロホルム、３７１ｎｍ検出波長）により精製した。分取した第一成分（ブロード）にＫＣＮ水溶液１００ｍＬを加え分液漏斗で激しく振とうし、蒸留水で３回洗浄した。無水硫酸ナトリウムで脱水後、溶媒を減圧留去してクロロホルム／ｎ−ヘキサンで再沈殿した。生成物をろ過、減圧乾燥し紫色粉末を得た。
収量 ８８．４ｍｇ ビタミンＢ12誘導体の修飾率 ５４％
Example 30
<Chemical modification of vitamin B 12 derivatives of the core-shell HBP (HPS-HEMA / PBMA) >
ol), HPS-HEMA / PBMA 101.4 mg (OH-containing group 2.12 × 10 −5 mol) and dimethylaminopyridine (DMAP) 13.0 mg (1.06 × 10 −4 mol) are added as the core-shell type HBP, Replaced with nitrogen. A dry N, N-dimethylformamide (DMF) solution (3 mL) was added and dissolved, and then 23.1 mg of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC / HCl) in an ice bath ( 1.21 × 10 −4 mol) was added, and the mixture was stirred at room temperature for 4 hours. Thereafter, 100 mL of chloroform was added and washed 3 times with distilled water. After dehydration with anhydrous sodium sulfate, the solution was concentrated and purified by GPC (eluent chloroform, 371 nm detection wavelength). 100 mL of KCN aqueous solution was added to the separated first component (broad), and the mixture was vigorously shaken with a separatory funnel and washed with distilled water three times. After dehydration with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure and reprecipitated with chloroform / n-hexane. The product was filtered and dried under reduced pressure to obtain a purple powder.
Yield 88.4mg vitamin B 12 derivative modification ratio of 54%
Claims (16)
Ｅは、下記の式（２）で表される繰り返し構造を表し、
Ａ1は下記の式（３）または式（４）
Ａ3はエーテル結合またはエステル結合を含んでいてもよい炭素原子数１ないし２０の直
鎖状、枝分かれ状または環状のアルキレン基を表し、
Ｘ1、Ｘ2、Ｘ3及びＸ4は、それぞれ独立して、水素原子、炭素原子数１ないし２０のアルキル基、または炭素原子数１から２０のアルコキシ基を表す。）で表される基を表し、
Ａ2はエーテル結合またはエステル結合を含んでいてもよい炭素原子数１ないし２０の直
鎖状、枝分かれ状または環状のアルキレン基を表し、
Ｒ1は水素原子またはメチル基を表し、
Ｒ2は水素原子、炭素原子数１ないし２０の直鎖状もしくは枝分かれ状のヒドロキシルア
ルキル基、炭素原子数３ないし２０の直鎖状もしくは枝分かれ状のエポキシ基を含むアルキル基、または式（５）
Ｒ3ないしＲ9のいずれか１つは、前記式（２）における酸素原子と共有結合する単結合を表し、前記Ａ2−Ｏ基と共有結合しないＲ3ないしＲ9はそれぞれ独立に水素原子または炭
素原子数１ないし２０のアルコキシ基を表し、
Ｙ1はシアノ基、ヒドロキシル基またはメチル基を表し、
Ｙ2はＣｏ原子に配位している水分子を表す。）で表されるビタミンＢ12化合物を表し（
ただし、Ｒ2のうち少なくとも１つ以上は前記式（５）で表されるビタミンＢ12化合物を
表す。）、
Ｚ1は、水素原子またはメチル基を表し、
ｎ及びｍは繰り返し単位の数であって、それぞれ独立して、２ないし１００，０００を表す。］ Vitamin B 12 modified core-shell type having a structure represented by the following formula (1) and having a weight average molecular weight of 2,000 to 20,000,000 measured in terms of polystyrene by gel permeation chromatography Hyperbranched polymer.
E represents a repeating structure represented by the following formula (2),
A 1 is the following formula (3) or formula (4)
A 3 represents a linear, branched or cyclic alkylene group having 1 to 20 carbon atoms which may contain an ether bond or an ester bond,
X 1 , X 2 , X 3 and X 4 each independently represent a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, or an alkoxy group having 1 to 20 carbon atoms. ) Represents a group represented by
A 2 represents a linear, branched or cyclic alkylene group having 1 to 20 carbon atoms which may contain an ether bond or an ester bond,
R 1 represents a hydrogen atom or a methyl group,
R 2 represents a hydrogen atom, a linear or branched hydroxylalkyl group having 1 to 20 carbon atoms, an alkyl group containing a linear or branched epoxy group having 3 to 20 carbon atoms, or the formula (5)
Any one of R 3 to R 9 represents a single bond covalently bonded to the oxygen atom in the formula (2), and R 3 to R 9 not covalently bonded to the A 2 —O group are each independently a hydrogen atom; Or an alkoxy group having 1 to 20 carbon atoms,
Y 1 represents a cyano group, a hydroxyl group or a methyl group,
Y 2 represents a water molecule coordinated to a Co atom. ) Represents a vitamin B 12 compound represented by (
However, at least one of R 2 represents a vitamin B 12 compound represented by the formula (5). ),
Z 1 represents a hydrogen atom or a methyl group,
n and m are the number of repeating units, and each independently represents 2 to 100,000. ]
表す、請求項１記載のビタミンＢ12修飾コア−シェル型ハイパーブランチポリマー。 The vitamin B 12 modified core-shell hyperbranch according to claim 1, wherein A 2 represents a group represented by-(CH 2 ) k- (wherein k represents an integer of 2 to 10). polymer.
Ｒ3ないしＲ8はそれぞれ独立に水素原子または炭素原子数１ないし２０のアルコキシ基を表し、
Ｙ1はシアノ基、ヒドロキシル基またはメチル基を表し、
Ｙ2はＣｏ原子に配位している水分子を表す。）で表される化合物であることを特徴とす
る請求項１記載のビタミンＢ12修飾コア−シェル型ハイパーブランチポリマー。 The vitamin B 12 compound is represented by the following formula (8):
R 3 to R 8 each independently represents a hydrogen atom or an alkoxy group having 1 to 20 carbon atoms,
Y 1 represents a cyano group, a hydroxyl group or a methyl group,
Y 2 represents a water molecule coordinated to a Co atom. The vitamin B 12 modified core-shell hyperbranched polymer according to claim 1, which is a compound represented by the formula:
Ａ3はエーテル結合またはエステル結合を含んでいてもよい炭素原子数１ないし２０の直
鎖状、枝分かれ状または環状のアルキレン基を表し、
Ｇはそれぞれ独立して、水素原子、またはＮ，Ｎ−ジエチルジチオカルバメート基を表し、
Ｅは、下記の式（１０）で表される基を表し
鎖状、枝分かれ状または環状のアルキレン基を表し、
Ｒ2は水素原子、炭素原子数１ないし２０の直鎖状もしくは枝分かれ状のヒドロキシルア
ルキル基、炭素原子数３ないし２０の直鎖状もしくは枝分かれ状のエポキシ基を含むアルキル基を表し、
Ｒ1は水素原子またはメチル基を表し、
ｎ及びｍは繰り返し単位の数であって、それぞれ独立に、２ないし１００，０００を表す。］ A core-shell hyperbranched polymer having a structure represented by the following formula (9) and having a weight average molecular weight of 2,000 to 20,000,000 as measured by gel permeation chromatography in terms of polystyrene.
A 3 represents a linear, branched or cyclic alkylene group having 1 to 20 carbon atoms which may contain an ether bond or an ester bond,
Each G independently represents a hydrogen atom or an N, N-diethyldithiocarbamate group;
E represents a group represented by the following formula (10).
R 2 represents a hydrogen atom, a linear or branched hydroxylalkyl group having 1 to 20 carbon atoms, an alkyl group containing a linear or branched epoxy group having 3 to 20 carbon atoms,
R 1 represents a hydrogen atom or a methyl group,
n and m are the number of repeating units, and each independently represents 2 to 100,000. ]
Ａ1は請求項１記載の式（３）または式（４）で表される基を表し、
Ａ2はエーテル結合またはエステル結合を含んでいてもよい炭素原子数１ないし２０の直
鎖状、枝分かれ状または環状のアルキレン基を表し、
Ｒ1は水素原子またはメチル基を表し、
Ｒ2は水素原子、炭素原子数１ないし２０の直鎖状もしくは枝分かれ状のヒドロキシルア
ルキル基、炭素原子数３ないし２０の直鎖状もしくは枝分かれ状のエポキシ基を含むアルキル基、または請求項１記載の式（５）で表されるビタミンＢ12化合物を表し（ただし、Ｒ2のうち少なくとも１つ以上は前記式（５）で表されるビタミンＢ12化合物を表す。）
、
Ｚ1は、水素原子またはメチル基を表し、
Ｚ2は、水素原子または炭素原子数１ないし２０の直鎖状もしくは枝分かれ状のアルキル
基を表し、
Ｚ3は、水素原子またはメチル基を表し、
Ｇは、それぞれ独立して、水素原子またはＮ，Ｎ−ジエチルジチオカルバメート基を表し、
ｐは繰り返し単位の数であって、それぞれ独立して、２ないし１００，０００を表す。] With the structure represented by the following formula (11) as a polymerization initiation site, a repeating unit having a linear structure represented by the following formula (12) and a repeating unit having a branched structure represented by the following formula (13): A linear chain structure represented by the formula (12), wherein the linear chain structure represented by the chemical formula (14) is bonded to the polymerization end portion of the polymer chain moiety. The total number of repeating units of the structure is an integer of 1 to 100,000, the total number of repeating units of the branched structure represented by the formula (13) is an integer of 2 to 100,000, and converted to polystyrene by gel permeation chromatography. Vitamin B 12 modified core-shell hyperbranched polymer having a weight average molecular weight of 2,000 to 20,000,000.
A 1 represents a group represented by formula (3) or formula (4) according to claim 1,
A 2 represents a linear, branched or cyclic alkylene group having 1 to 20 carbon atoms which may contain an ether bond or an ester bond,
R 1 represents a hydrogen atom or a methyl group,
2. R 2 is a hydrogen atom, a linear or branched hydroxylalkyl group having 1 to 20 carbon atoms, an alkyl group containing a linear or branched epoxy group having 3 to 20 carbon atoms, or claim 1 The vitamin B 12 compound represented by the formula (5) is represented (however, at least one of R 2 represents the vitamin B 12 compound represented by the formula (5)).
,
Z 1 represents a hydrogen atom or a methyl group,
Z 2 represents a hydrogen atom or a linear or branched alkyl group having 1 to 20 carbon atoms,
Z 3 represents a hydrogen atom or a methyl group,
Each G independently represents a hydrogen atom or an N, N-diethyldithiocarbamate group;
p is the number of repeating units, and each independently represents 2 to 100,000. ]
載のビタミンＢ12修飾コア−シェル型ハイパーブランチポリマー。 The vitamin B 12 modified core-shell hyperbranched polymer according to claim 10, wherein A 1 represents a group represented by formula (6) or formula (7) according to claim 2.
表す、請求項１０記載のビタミンＢ12修飾コア−シェル型ハイパーブランチポリマー。 The vitamin B 12 modified core-shell hyperbranch according to claim 10, wherein A 2 represents a group represented by-(CH 2 ) k- (wherein k represents an integer of 2 to 10). polymer.
The radical type organic synthesis reaction catalyst according to claim 14, which is used for promoting a carbon-carbon bond reaction.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2009053934A JP5263828B2 (en) | 2008-03-11 | 2009-03-06 | Vitamin B12 modified core-shell hyperbranched polymer and dehalogenation catalyst |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2008061344 | 2008-03-11 | ||
| JP2008061344 | 2008-03-11 | ||
| JP2009053934A JP5263828B2 (en) | 2008-03-11 | 2009-03-06 | Vitamin B12 modified core-shell hyperbranched polymer and dehalogenation catalyst |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009242787A true JP2009242787A (en) | 2009-10-22 |
| JP5263828B2 JP5263828B2 (en) | 2013-08-14 |
Family
ID=41305041
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009053934A Expired - Fee Related JP5263828B2 (en) | 2008-03-11 | 2009-03-06 | Vitamin B12 modified core-shell hyperbranched polymer and dehalogenation catalyst |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP5263828B2 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010101252A1 (en) * | 2009-03-06 | 2010-09-10 | 日産化学工業株式会社 | Hyperbranched polymer production method |
| WO2010101254A1 (en) * | 2009-03-06 | 2010-09-10 | 日産化学工業株式会社 | Hyperbranched polymer production method |
| CN102200527A (en) * | 2011-03-23 | 2011-09-28 | 天津市兰力科化学电子高技术有限公司 | Cyclic voltammetry for detecting vitamin content in blood sample |
| WO2012074051A1 (en) * | 2010-12-01 | 2012-06-07 | 国立大学法人九州大学 | Fluorinated hyperbranched polymer and process for production thereof |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03504450A (en) * | 1988-05-09 | 1991-10-03 | ザ・パブリツク・ヘルス・ラボラタリイ・サーヴイス・ボード | Use of metal chelate complexes in dehalogenation |
| JP2004256563A (en) * | 2003-02-24 | 2004-09-16 | Shiseido Co Ltd | Production method for star polymer |
| JP2006191947A (en) * | 2005-01-11 | 2006-07-27 | Sumitomo Chemical Co Ltd | Dehalogenation method of organic halide |
| WO2006101003A1 (en) * | 2005-03-18 | 2006-09-28 | National University Corporation The University Of Electro-Communications | Photosensitive composition containing organic fine particles |
| WO2007148578A1 (en) * | 2006-06-19 | 2007-12-27 | Tokyo Institute Of Technology | Hyperbranched polymer and method for producing the same |
| WO2008081894A1 (en) * | 2006-12-28 | 2008-07-10 | Lion Corporation | Method for synthesis of core-shell-type hyperbranched polymer |
| JP2008266571A (en) * | 2007-01-05 | 2008-11-06 | Kyushu Univ | Vitamin b12 modified hyperbranched polymer and dehaloganation catalyst |
-
2009
- 2009-03-06 JP JP2009053934A patent/JP5263828B2/en not_active Expired - Fee Related
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03504450A (en) * | 1988-05-09 | 1991-10-03 | ザ・パブリツク・ヘルス・ラボラタリイ・サーヴイス・ボード | Use of metal chelate complexes in dehalogenation |
| JP2004256563A (en) * | 2003-02-24 | 2004-09-16 | Shiseido Co Ltd | Production method for star polymer |
| JP2006191947A (en) * | 2005-01-11 | 2006-07-27 | Sumitomo Chemical Co Ltd | Dehalogenation method of organic halide |
| WO2006101003A1 (en) * | 2005-03-18 | 2006-09-28 | National University Corporation The University Of Electro-Communications | Photosensitive composition containing organic fine particles |
| WO2007148578A1 (en) * | 2006-06-19 | 2007-12-27 | Tokyo Institute Of Technology | Hyperbranched polymer and method for producing the same |
| WO2008081894A1 (en) * | 2006-12-28 | 2008-07-10 | Lion Corporation | Method for synthesis of core-shell-type hyperbranched polymer |
| JP2008266571A (en) * | 2007-01-05 | 2008-11-06 | Kyushu Univ | Vitamin b12 modified hyperbranched polymer and dehaloganation catalyst |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010101252A1 (en) * | 2009-03-06 | 2010-09-10 | 日産化学工業株式会社 | Hyperbranched polymer production method |
| WO2010101254A1 (en) * | 2009-03-06 | 2010-09-10 | 日産化学工業株式会社 | Hyperbranched polymer production method |
| JP5594482B2 (en) * | 2009-03-06 | 2014-09-24 | 日産化学工業株式会社 | Method for producing hyperbranched polymer |
| WO2012074051A1 (en) * | 2010-12-01 | 2012-06-07 | 国立大学法人九州大学 | Fluorinated hyperbranched polymer and process for production thereof |
| JP5872484B2 (en) * | 2010-12-01 | 2016-03-01 | 国立大学法人九州大学 | Fluorine-containing hyperbranched polymer and method for producing the same |
| CN102200527A (en) * | 2011-03-23 | 2011-09-28 | 天津市兰力科化学电子高技术有限公司 | Cyclic voltammetry for detecting vitamin content in blood sample |
Also Published As
| Publication number | Publication date |
|---|---|
| JP5263828B2 (en) | 2013-08-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Qin et al. | Click polymerization | |
| Xu et al. | Designing fluorene-based conjugated microporous polymers for blue light-driven photocatalytic selective oxidation of amines with oxygen | |
| JP2009024147A (en) | Norbornene monomer having fluorene group and polymer thereof | |
| JP5263828B2 (en) | Vitamin B12 modified core-shell hyperbranched polymer and dehalogenation catalyst | |
| US20100249350A1 (en) | Hyperbranched polymer having nitroxyl group | |
| Xie et al. | Toward high-performance dibenzo [g, p] chrysene-based conjugated polymer photocatalysts for photocatalytic hydrogen production through donor-acceptor-acceptor structure design | |
| Balaji et al. | Synthesis and characterization of photocrosslinkable functional polymer having pendant chalcone moiety | |
| Song et al. | A bridge-like polymer synthesized by tandem metathesis cyclopolymerization and acyclic diene metathesis polymerization | |
| JP5348656B2 (en) | Vitamin B12 modified hyperbranched polymer and dehalogenation catalyst | |
| Campalani et al. | Carbon dots as green photocatalysts for atom transfer radical polymerization of methacrylates | |
| Sutthasupa et al. | Ring‐opening metathesis polymerization of amino acid‐functionalized norbornene derivatives | |
| Troiano et al. | ROMP of norbornene and oxanorbornene derivatives with pendant fluorophore carbazole and coumarin groups | |
| Bicak et al. | Vinylamine polymer via chemical modification of PVC | |
| Diederich | Functional acetylenic molecular architecture | |
| Pijnenburg et al. | The role of the dendritic support in the catalytic performance of peripheral pincer Pd-complexes | |
| Watson et al. | The synthesis and ring-opening metathesis polymerization of an amphiphilic redox-active norbornene | |
| Park et al. | Synthesis and application of terpolymer bearing cyclic carbonate and cinnamoyl groups | |
| Yamaguchi et al. | Enzymatic polymerization to give poly (dihydroxynaphthalene) s and their photoluminescent aluminum complexes | |
| Fiset et al. | Synthesis, characterization and modification of azide-containing dendronized diblock copolymers | |
| Miftakhov et al. | Fullerene containing norbornenes: synthesis and ring-opening metathesis polymerization | |
| Ueda et al. | Synthesis of hydroxyphenylglycine-derived novel poly (silylenevinylenephenyleneethynylene) s | |
| US11359049B2 (en) | Gold catalyzed polymerization reactions of unsaturated substrates | |
| Lee et al. | Synthesis and Characterization of a Novel Electron-Acceptor Polymer Based on a Poly (1, 6-heptadyine) Main Chain | |
| Lee et al. | Synthesis of Unsymmetrically. alpha.-Substituted Poly (dipropargyl ether) Derivatives by Metathesis Catalysts | |
| Meng et al. | Aromatic disulfide polymers back to macrocyclic disulfide oligomers via cyclo-depolymerization reaction |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20120302 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20120302 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20121107 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20121212 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130206 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20130403 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130424 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 Ref document number: 5263828 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
| S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| LAPS | Cancellation because of no payment of annual fees |