JP4161057B2 - Method for producing carbonyl compound - Google Patents
Method for producing carbonyl compound Download PDFInfo
- Publication number
- JP4161057B2 JP4161057B2 JP2004240287A JP2004240287A JP4161057B2 JP 4161057 B2 JP4161057 B2 JP 4161057B2 JP 2004240287 A JP2004240287 A JP 2004240287A JP 2004240287 A JP2004240287 A JP 2004240287A JP 4161057 B2 JP4161057 B2 JP 4161057B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- reaction
- group
- carbonyl compound
- carbonyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000001728 carbonyl compounds Chemical class 0.000 title claims description 72
- 238000004519 manufacturing process Methods 0.000 title claims description 25
- 150000001875 compounds Chemical class 0.000 claims description 58
- 150000003564 thiocarbonyl compounds Chemical class 0.000 claims description 40
- 239000003054 catalyst Substances 0.000 claims description 31
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 21
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 20
- 229910001882 dioxygen Inorganic materials 0.000 claims description 20
- 239000002798 polar solvent Substances 0.000 claims description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 16
- 229910052802 copper Inorganic materials 0.000 claims description 8
- 239000010949 copper Substances 0.000 claims description 8
- -1 copper halide Chemical class 0.000 claims description 7
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 7
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 5
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical group [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 5
- 229910021592 Copper(II) chloride Inorganic materials 0.000 claims description 3
- JIDMEYQIXXJQCC-UHFFFAOYSA-L copper;2,2,2-trifluoroacetate Chemical compound [Cu+2].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F JIDMEYQIXXJQCC-UHFFFAOYSA-L 0.000 claims description 3
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 description 65
- 239000000243 solution Substances 0.000 description 23
- 238000005160 1H NMR spectroscopy Methods 0.000 description 17
- 239000007795 chemical reaction product Substances 0.000 description 16
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 14
- 229910052760 oxygen Inorganic materials 0.000 description 14
- 239000001301 oxygen Substances 0.000 description 14
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 12
- 239000000376 reactant Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 10
- 229910052751 metal Inorganic materials 0.000 description 9
- 239000002184 metal Substances 0.000 description 9
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 9
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 8
- 238000006477 desulfuration reaction Methods 0.000 description 8
- 230000023556 desulfurization Effects 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 7
- GMOICCILTLBRTM-UHFFFAOYSA-N n-benzylbenzenecarbothioamide Chemical compound C=1C=CC=CC=1C(=S)NCC1=CC=CC=C1 GMOICCILTLBRTM-UHFFFAOYSA-N 0.000 description 7
- 230000035484 reaction time Effects 0.000 description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 5
- 239000012295 chemical reaction liquid Substances 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 238000001819 mass spectrum Methods 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 125000004430 oxygen atom Chemical group O* 0.000 description 5
- 229910052711 selenium Inorganic materials 0.000 description 5
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 4
- 229940126657 Compound 17 Drugs 0.000 description 4
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 229910017052 cobalt Inorganic materials 0.000 description 4
- 239000010941 cobalt Substances 0.000 description 4
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 4
- 229940125904 compound 1 Drugs 0.000 description 4
- 239000012259 ether extract Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 150000002739 metals Chemical class 0.000 description 4
- 229910052759 nickel Inorganic materials 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 3
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 229940126142 compound 16 Drugs 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000006213 oxygenation reaction Methods 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 230000000737 periodic effect Effects 0.000 description 3
- 239000011669 selenium Substances 0.000 description 3
- 229910052709 silver Inorganic materials 0.000 description 3
- 239000004332 silver Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 2
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 2
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 229940126062 Compound A Drugs 0.000 description 2
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
- 235000002597 Solanum melongena Nutrition 0.000 description 2
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
- 229940125797 compound 12 Drugs 0.000 description 2
- 229940126543 compound 14 Drugs 0.000 description 2
- 229940125758 compound 15 Drugs 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- LKQUCICFTHBFAL-UHFFFAOYSA-N n-benzylbenzamide Chemical compound C=1C=CC=CC=1C(=O)NCC1=CC=CC=C1 LKQUCICFTHBFAL-UHFFFAOYSA-N 0.000 description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 1
- OPUPBQQWLWFCPU-UHFFFAOYSA-N 2-benzylbenzamide Chemical compound NC(=O)C1=CC=CC=C1CC1=CC=CC=C1 OPUPBQQWLWFCPU-UHFFFAOYSA-N 0.000 description 1
- FQCJWCKLCVMCFK-UHFFFAOYSA-N 2-phenyl-1-pyrrolidin-1-ylpent-4-en-1-one Chemical compound C=1C=CC=CC=1C(CC=C)C(=O)N1CCCC1 FQCJWCKLCVMCFK-UHFFFAOYSA-N 0.000 description 1
- YHLVEHXOBBYATA-UHFFFAOYSA-N 5,5-dimethyl-1,3-diazinan-2-one Chemical compound CC1(C)CNC(=O)NC1 YHLVEHXOBBYATA-UHFFFAOYSA-N 0.000 description 1
- 229930008564 C01BA04 - Sparteine Natural products 0.000 description 1
- 229910021580 Cobalt(II) chloride Inorganic materials 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- SLRCCWJSBJZJBV-UHFFFAOYSA-N alpha-isosparteine Natural products C1N2CCCCC2C2CN3CCCCC3C1C2 SLRCCWJSBJZJBV-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- FBXVOTBTGXARNA-UHFFFAOYSA-N bismuth;trinitrate;pentahydrate Chemical compound O.O.O.O.O.[Bi+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O FBXVOTBTGXARNA-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
- XFLREUZYPXVKMW-UHFFFAOYSA-N butyl n-benzoylcarbamate Chemical compound CCCCOC(=O)NC(=O)C1=CC=CC=C1 XFLREUZYPXVKMW-UHFFFAOYSA-N 0.000 description 1
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000001948 isotopic labelling Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- MKDCJIXTFIFFJV-UHFFFAOYSA-N n,n-dibenzyl-2,2-dimethylpropanamide Chemical compound C=1C=CC=CC=1CN(C(=O)C(C)(C)C)CC1=CC=CC=C1 MKDCJIXTFIFFJV-UHFFFAOYSA-N 0.000 description 1
- SEXRCGYUTZHHOX-UHFFFAOYSA-N n,n-dibenzyl-2-methylpropanamide Chemical compound C=1C=CC=CC=1CN(C(=O)C(C)C)CC1=CC=CC=C1 SEXRCGYUTZHHOX-UHFFFAOYSA-N 0.000 description 1
- CTIYZFCOYKGRKC-UHFFFAOYSA-N n,n-dibenzylpropanamide Chemical compound C=1C=CC=CC=1CN(C(=O)CC)CC1=CC=CC=C1 CTIYZFCOYKGRKC-UHFFFAOYSA-N 0.000 description 1
- HYRDTOIPWXXZCJ-UHFFFAOYSA-N n-benzyl-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NCC1=CC=CC=C1 HYRDTOIPWXXZCJ-UHFFFAOYSA-N 0.000 description 1
- QHQKYJAIOSKSFL-UHFFFAOYSA-N n-benzyl-2-methylpropanamide Chemical compound CC(C)C(=O)NCC1=CC=CC=C1 QHQKYJAIOSKSFL-UHFFFAOYSA-N 0.000 description 1
- XCRBOSJQBAFSMZ-UHFFFAOYSA-N n-benzyl-4-fluorobenzamide Chemical compound C1=CC(F)=CC=C1C(=O)NCC1=CC=CC=C1 XCRBOSJQBAFSMZ-UHFFFAOYSA-N 0.000 description 1
- GEFZSLMGZREDTO-UHFFFAOYSA-N n-benzyl-4-methoxybenzamide Chemical compound C1=CC(OC)=CC=C1C(=O)NCC1=CC=CC=C1 GEFZSLMGZREDTO-UHFFFAOYSA-N 0.000 description 1
- QIULRTIURUDCGH-UHFFFAOYSA-N n-benzyl-4-methylbenzamide Chemical compound C1=CC(C)=CC=C1C(=O)NCC1=CC=CC=C1 QIULRTIURUDCGH-UHFFFAOYSA-N 0.000 description 1
- ZFNAETKJDHAQEN-UHFFFAOYSA-N n-benzylpropanamide Chemical compound CCC(=O)NCC1=CC=CC=C1 ZFNAETKJDHAQEN-UHFFFAOYSA-N 0.000 description 1
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
- 150000002829 nitrogen Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- CZARCWHPQGJOBF-UHFFFAOYSA-N o-butyl n-benzoylcarbamothioate Chemical compound CCCCOC(=S)NC(=O)C1=CC=CC=C1 CZARCWHPQGJOBF-UHFFFAOYSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- WOHDXQQIBRMRFA-UHFFFAOYSA-N phenyl 4-methylbenzoate Chemical compound C1=CC(C)=CC=C1C(=O)OC1=CC=CC=C1 WOHDXQQIBRMRFA-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 description 1
- SLRCCWJSBJZJBV-AJNGGQMLSA-N sparteine Chemical compound C1N2CCCC[C@H]2[C@@H]2CN3CCCC[C@H]3[C@H]1C2 SLRCCWJSBJZJBV-AJNGGQMLSA-N 0.000 description 1
- 229960001945 sparteine Drugs 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000013022 venting Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
本発明は、各種化学製品や医薬品、農薬品等に用いられるカルボニル化合物の製造方法に関するものである。 The present invention relates to a method for producing a carbonyl compound used for various chemical products, pharmaceuticals, agricultural chemicals and the like.
従来、カルボニル化合物の製造方法としては、チオカルボニル化合物に硝酸ビスマス五水和物を反応させることによりカルボニル化合物を得る方法が知られている（例えば、非特許文献１参照。）。また、窒素雰囲気下で、チオカルボニル化合物に塩化銅（Ｉ）及び水酸化ナトリウム水溶液を反応させることによりカルボニル化合物を得る方法が知られている（例えば、非特許文献２参照。）。
本発明は、本研究者らの鋭意研究の結果、カルボニル化合物の新規な合成方法を見出したことによりなされたものである。その目的とするところは、カルボニル化合物を容易に製造することが可能なカルボニル化合物の製造方法を提供することにある。 The present invention has been made by finding a novel synthesis method of a carbonyl compound as a result of diligent research by the present researchers. An object of the invention is to provide a method for producing a carbonyl compound capable of easily producing a carbonyl compound.
上記の目的を達成するために、請求項１に記載の発明のカルボニル化合物の製造方法は、チオカルボニル化合物又はセレノカルボニル化合物と分子状酸素とを、銅ハロゲン化物及びトリフルオロ酢酸銅（ＩＩ）から選ばれる少なくとも一種を含む触媒の存在下、極性溶媒中で反応させることを要旨とする。 In order to achieve the above object, a method for producing a carbonyl compound according to the first aspect of the present invention includes a thiocarbonyl compound or a selenocarbonyl compound and molecular oxygen obtained from copper halide and copper (II) trifluoroacetate. The gist is to perform the reaction in a polar solvent in the presence of a catalyst containing at least one selected.
請求項２に記載の発明のカルボニル化合物の製造方法は、請求項１に記載の発明において、前記銅ハロゲン化物が塩化銅（Ｉ）、塩化銅（ＩＩ）又はヨウ化銅（Ｉ）であることを要旨とする。 The method for producing a carbonyl compound according to claim 2 is the method according to claim 1, wherein the copper halide is copper (I) chloride, copper (II) chloride or copper (I) iodide. Is the gist.
請求項３に記載の発明のカルボニル化合物の製造方法は、請求項１又は請求項２に記載の発明において、前記極性溶媒には、触媒に対して少なくとも１〜１０モル当量のジメチルホルムアミド又はジメチルスルホキシドが含有されることを要旨とする。 The method for producing a carbonyl compound according to a third aspect of the present invention is the method according to the first or second aspect, wherein the polar solvent includes at least 1 to 10 molar equivalents of dimethylformamide or dimethylsulfoxide with respect to the catalyst. Is included .
本発明によれば、カルボニル化合物を容易に製造することが可能なカルボニル化合物の製造方法を提供することができる。 ADVANTAGE OF THE INVENTION According to this invention, the manufacturing method of the carbonyl compound which can manufacture a carbonyl compound easily can be provided.
以下、本発明の実施形態について詳細に説明する。
実施形態のカルボニル化合物は、カルボニル基を有する化合物、即ち下記一般式（１）で示される構造を有する化合物である。尚、以下の説明において、Ｐｈはフェニル基を示し、Ｍｅはメチル基を示し、Ｐｒはプロピル基を示し、Ｂｕはブチル基を示し、Ｂｎはベンジル基（フェニルメチル基）を示す。
Hereinafter, embodiments of the present invention will be described in detail.
The carbonyl compound of the embodiment is a compound having a carbonyl group, that is, a compound having a structure represented by the following general formula (1). In the following description, Ph represents a phenyl group, Me represents a methyl group, Pr represents a propyl group, Bu represents a butyl group, and Bn represents a benzyl group (phenylmethyl group).
アルキル基としては、メチル基、エチル基、イソプロピル基（ｉ−Ｐｒ）等のプロピル基、ｔｅｒｔ−ブチル基（ｔ−Ｂｕ）等のブチル基等が挙げられる。アリール基としては、メトキシフェニル基、メチルフェニル基、α、α、α−トリフルオロメチルフェニル基等が挙げられる。アルケニル基としてはα−アリル−ベンジル基等が挙げられる。アルキニル基としてはエチニル基等が挙げられる。アミノ基としては、アミノ基(-NH2)自身の他、ジメチルアミノ基、ベンジルアミノ基、ジベンジルアミノ基、ピロリジル基等が挙げられる。アルコキシ基としてはメトキシ基、エトキシ基、ｉ−プロポキシ基等のプロポキシ基、ｔｅｒｔ−ブトキシ基等のブトキシ基、フェノキシ基等が挙げられる。このカルボニル化合物は、各種化学製品や医薬品、農薬品等に用いられる。例えば、カルボニル化合物であるタキソールは、抗腫瘍活性を有しており、抗癌剤として用いられる。 Examples of the alkyl group include a propyl group such as a methyl group, an ethyl group, and an isopropyl group (i-Pr), and a butyl group such as a tert-butyl group (t-Bu). Examples of the aryl group include a methoxyphenyl group, a methylphenyl group, α, α, α-trifluoromethylphenyl group and the like. Examples of the alkenyl group include α-allyl-benzyl group. An ethynyl group etc. are mentioned as an alkynyl group. Examples of the amino group include an amino group (—NH 2 ) itself, a dimethylamino group, a benzylamino group, a dibenzylamino group, and a pyrrolidyl group. Examples of the alkoxy group include a methoxy group, an ethoxy group, a propoxy group such as an i-propoxy group, a butoxy group such as a tert-butoxy group, and a phenoxy group. This carbonyl compound is used in various chemical products, pharmaceuticals, agricultural chemicals, and the like. For example, taxol, which is a carbonyl compound, has antitumor activity and is used as an anticancer agent.
カルボニル化合物は、チオカルボニル化合物及び分子状酸素（Ｏ2）を、触媒の存在下、極性溶媒中で反応させることにより製造される。また、カルボニル化合物は、セレノカルボニル化合物及び分子状酸素を、触媒の存在下、極性溶媒中で反応させることにより製造される。即ち、カルボニル化合物は、チオカルボニル化合物又はセレノカルボニル化合物、触媒及び極性溶媒を配合して反応液を調製した後、該反応液に分子状酸素を溶解させるとともに同反応液を加熱することにより製造される。このとき、カルボニル化合物は、チオカルボニル化合物の脱硫酸素化反応又はセレノカルボニル化合物の脱セレノ酸素化反応により得られる。さらにこのとき、前記脱硫酸素化反応又は脱セレノ酸素化反応の副生成物として硫黄又はセレンが生成される。 The carbonyl compound is produced by reacting a thiocarbonyl compound and molecular oxygen (O 2 ) in a polar solvent in the presence of a catalyst. A carbonyl compound is produced by reacting a selenocarbonyl compound and molecular oxygen in a polar solvent in the presence of a catalyst. That is, a carbonyl compound is produced by preparing a reaction liquid by mixing a thiocarbonyl compound or a selenocarbonyl compound, a catalyst and a polar solvent, and then dissolving molecular oxygen in the reaction liquid and heating the reaction liquid. The At this time, the carbonyl compound is obtained by a desulfurization reaction of a thiocarbonyl compound or a deselenooxygenation reaction of a selenocarbonyl compound. Further, at this time, sulfur or selenium is produced as a by-product of the desulfurization reaction or deseleno oxygenation reaction.
チオカルボニル化合物は、前記一般式（１）において、酸素原子の代わりに硫黄原子が炭素原子に結合した構造を有する化合物である。一方、セレノカルボニル化合物は、前記一般式（１）において、酸素原子の代わりにセレン原子が炭素原子に結合した構造を有する化合物である。これらチオカルボニル化合物及びセレノカルボニル化合物は、それぞれ単独で反応物（出発物質）を構成してもよいし、それらが組み合わされて反応物を構成してもよい。チオカルボニル化合物及びセレノカルボニル化合物の組み合わせから反応物が構成されるときには、各化合物由来のカルボニル化合物が同時に製造される。さらにチオカルボニル化合物及びセレノカルボニル化合物は、それらの具体例の内の一種類の化合物のみで反応物を構成してもよいし、二種以上の化合物から反応物を構成してもよい。二種以上の化合物から反応物が構成されるときには、二種以上のカルボニル化合物が同時に製造される。 The thiocarbonyl compound is a compound having a structure in which a sulfur atom is bonded to a carbon atom in place of the oxygen atom in the general formula (1). On the other hand, the selenocarbonyl compound is a compound having a structure in which a selenium atom is bonded to a carbon atom in place of the oxygen atom in the general formula (1). These thiocarbonyl compounds and selenocarbonyl compounds may each constitute a reactant (starting material) alone, or may be combined to constitute a reactant. When the reactant is composed of a combination of a thiocarbonyl compound and a selenocarbonyl compound, a carbonyl compound derived from each compound is simultaneously produced. Further, the thiocarbonyl compound and the selenocarbonyl compound may constitute a reactant with only one kind of compounds among those specific examples, or may constitute a reactant with two or more kinds of compounds. When a reactant is composed of two or more compounds, two or more carbonyl compounds are produced simultaneously.
分子状酸素は、チオカルボニル化合物及びセレノカルボニル化合物の酸化剤として作用し、脱硫酸素化反応及び脱セレノ酸素化反応を行う。分子状酸素を構成する酸素原子の質量数は通常１６である。分子状酸素の反応液への溶解は、酸素ガス雰囲気下で反応液を静置若しくは撹拌する、又は反応液中に酸素ガスを通気することにより行われる。 Molecular oxygen acts as an oxidizing agent for thiocarbonyl compounds and selenocarbonyl compounds, and performs desulfurization and deselenooxygenation reactions. The mass number of oxygen atoms constituting molecular oxygen is usually 16. The molecular oxygen is dissolved in the reaction solution by standing or stirring the reaction solution in an oxygen gas atmosphere or by passing oxygen gas through the reaction solution.
触媒は、脱硫酸素化反応及び脱セレノ酸素化反応を促進する。この触媒は、周期律表の第８族に属する金属、第９族に属する金属、第１０族に属する金属、及び第１１族に属する金属よりなる群から選ばれる少なくとも一種を含む。周期律表の第８族に属する金属としては鉄等が挙げられ、鉄を含む触媒としては塩化鉄（ＩＩＩ）等が挙げられる。第９族に属する金属としてはコバルト等が挙げられ、コバルトを含む触媒としては塩化コバルト（ＩＩ）等が挙げられる。第１０族に属する金属としてはニッケルやパラジウム等が挙げられる。ニッケルを含む触媒としては塩化ニッケル（ＩＩ）等が挙げられ、パラジウムを含む触媒としては塩化パラジウム（ＩＩ）が挙げられる。第１１族に属する金属としては銅や銀等が挙げられる。銅を含む触媒としては塩化銅（Ｉ）、塩化銅（ＩＩ）、ヨウ化銅（Ｉ）、トリフルオロ酢酸銅（ＩＩ）等が挙げられ、銀を含む触媒としては酢酸銀（Ｉ）等が挙げられる。 The catalyst promotes desulfation and deseleno oxygenation reactions. The catalyst includes at least one selected from the group consisting of metals belonging to Group 8 of the periodic table, metals belonging to Group 9, metals belonging to Group 10, and metals belonging to Group 11. Examples of the metal belonging to Group 8 of the periodic table include iron, and examples of the catalyst containing iron include iron (III) chloride. Examples of the metal belonging to Group 9 include cobalt, and examples of the catalyst containing cobalt include cobalt (II) chloride. Examples of the metal belonging to Group 10 include nickel and palladium. Examples of the catalyst containing nickel include nickel (II) chloride, and examples of the catalyst containing palladium include palladium (II) chloride. Examples of the metal belonging to Group 11 include copper and silver. Examples of the catalyst containing copper include copper (I) chloride, copper (II) chloride, copper iodide (I), and copper (II) trifluoroacetate. Examples of the catalyst containing silver include silver (I) acetate. Can be mentioned.
触媒は、前記各反応の促進効果が高いために、銅、銀、鉄、コバルト、及びニッケルよるなる群から選ばれる少なくとも一種を含むことが好ましく、銅を含むことがより好ましく、塩化銅（Ｉ）を含むことが最も好ましい。反応液中の触媒の含有量は１〜２０モル％が好ましく、５〜２０モル％がより好ましい。触媒は、その含有量が１モル％未満では前記各反応を十分に促進することができず、逆に２０モル％を超えても各反応をそれ以上促進することができない。 The catalyst preferably contains at least one selected from the group consisting of copper, silver, iron, cobalt, and nickel, more preferably contains copper, and copper chloride (I Most preferably). 1-20 mol% is preferable and, as for content of the catalyst in a reaction liquid, 5-20 mol% is more preferable. When the content of the catalyst is less than 1 mol%, the above reactions cannot be promoted sufficiently. Conversely, when the content exceeds 20 mol%, the reactions cannot be further promoted.
極性溶媒は、チオカルボニル化合物又はセレノカルボニル化合物と分子状酸素とを反応させる。極性溶媒としては、低極性溶媒であるトルエンやテトラヒドロフラン、高極性溶媒であるジメチルホルムアミド（ＤＭＦ）やジメチルスルホキシド（ＤＭＳＯ）が挙げられる。これらは単独で用いられてもよいし、二種以上が組み合わされて用いられてもよい。これらの中でも、ＤＭＦ又はＤＭＳＯが、チオカルボニル化合物又はセレノカルボニル化合物と分子状酸素との反応効率を高めることができるために好ましい。このため、極性溶媒としてトルエンやテトラヒドロフランを用いるときには、それらにＤＭＦ又はＤＭＳＯを少量（触媒に対して１〜１０モル当量）加えるのが好ましい。 The polar solvent reacts the thiocarbonyl compound or selenocarbonyl compound with molecular oxygen. Examples of the polar solvent include toluene and tetrahydrofuran, which are low polarity solvents, and dimethylformamide (DMF) and dimethyl sulfoxide (DMSO), which are high polarity solvents. These may be used alone or in combination of two or more. Among these, DMF or DMSO is preferable because the reaction efficiency between the thiocarbonyl compound or the selenocarbonyl compound and molecular oxygen can be increased. For this reason, when using toluene or tetrahydrofuran as a polar solvent, it is preferable to add a small amount of DMF or DMSO (1 to 10 molar equivalents relative to the catalyst) to them.
反応液は、その他の添加成分として含窒素二座配位子等の配位性化合物を含有することが好ましい。この配位性化合物は、極性溶媒として前記低極性溶媒が用いられるときには、該低極性溶媒中で前記各反応を促進する。また、触媒がコバルト、ニッケル又はパラジウムを含むときには、該触媒の各反応の促進効果を高める。さらに配位性化合物は、キラリティーを有しているときには光学活性を有するカルボニル化合物を反応速度論的に容易に分離する。配位性化合物としては、２，２’−ビピリジン、二座飽和型窒素配位子であるスパルテイン、下記一般式（２）で示される構造を有するビスオキサゾリン等が挙げられる。尚、下記一般式（２）において、Ｒ3はｉ−Ｐｒ、ｔ−Ｂｕ、Ｂｎ等を示す。 The reaction solution preferably contains a coordinating compound such as a nitrogen-containing bidentate ligand as another additive component. This coordinating compound promotes each reaction in the low polarity solvent when the low polarity solvent is used as the polar solvent. Moreover, when a catalyst contains cobalt, nickel, or palladium, the promotion effect of each reaction of the catalyst is enhanced. Further, when the coordination compound has chirality, the carbonyl compound having optical activity is easily separated from the reaction kinetics. Examples of the coordination compound include 2,2′-bipyridine, sparteine which is a bidentate saturated nitrogen ligand, and bisoxazoline having a structure represented by the following general formula (2). In the following general formula (2), R 3 represents i-Pr, t-Bu, Bn or the like.
反応液の加熱温度、即ち前記各反応の反応温度は５０〜８０℃が好ましい。各反応は、反応温度が５０℃未満では反応効率が低下するおそれがあり、８０℃を超えても反応効率をそれ以上高めることができない。 The heating temperature of the reaction solution, that is, the reaction temperature of each reaction is preferably 50 to 80 ° C. In each reaction, if the reaction temperature is less than 50 ° C., the reaction efficiency may decrease, and if it exceeds 80 ° C., the reaction efficiency cannot be further increased.
従って、実施形態の製造方法では、前記触媒及び極性溶媒を用いることにより、チオカルボニル化合物又はセレノカルボニル化合物と分子状酸素とを効率よく反応させることができる。分子状酸素は、その取扱いが容易であるとともに入手し易い。さらに実施形態の製造方法では、チオカルボニル化合物又はセレノカルボニル化合物から一段階の反応でカルボニル化合物を製造することができるとともに、硫黄やセレンのみが副生成物として生成される。これら硫黄及びセレンは、反応液からの除去が容易であるとともに、一般的なカルボニル化合物の製造時に発生する副生成物に比べて環境に対する配慮の面から好ましい。このため、実施形態の製造方法は、カルボニル化合物を容易に製造することが可能である。 Therefore, in the production method of the embodiment, the thiocarbonyl compound or selenocarbonyl compound and molecular oxygen can be efficiently reacted by using the catalyst and the polar solvent. Molecular oxygen is easy to handle and easy to obtain. Furthermore, in the production method of the embodiment, a carbonyl compound can be produced from a thiocarbonyl compound or a selenocarbonyl compound by a one-step reaction, and only sulfur and selenium are produced as by-products. These sulfur and selenium are preferable from the viewpoint of environmental considerations as compared with the by-products generated during the production of general carbonyl compounds, while being easily removed from the reaction solution. For this reason, the manufacturing method of embodiment can manufacture a carbonyl compound easily.
次に、実施例、参考例及び比較例を挙げて前記実施形態をさらに具体的に説明する。
（実施例１〜７、１２及び１３、参考例８〜１１、並びに比較例１及び２）
実施例１においては、20mlの二口ナスフラスコ内で、チオカルボニル化合物としてのN-ベンジル-ベンゼンカルボチオアミド0.500mmol（114mg）、触媒としての塩化銅（Ｉ）0.100mmol（9.9mg）及び極性溶媒としての0.5mlのDMSOを配合して反応液を調製した。次いで、前記二口ナスフラスコ内の空気を酸素置換した後、反応液を80℃に加熱するとともに撹拌した。反応液の加熱及び撹拌開始後、一定時間が経過する毎に、ヘキサンと酢酸エチルとが体積比で５：１の展開溶媒を用いた薄層クロマトグラフィ−（TLC）により、反応の進行を確認した。TLCにおいて反応物のN-ベンジル-ベンゼンカルボチオアミドの存在が確認できなくなった後、飽和塩化アンモニウム水溶液及びエーテルを用いた反応液のエーテル抽出を３回繰返して、エーテル抽出液を得た。続いて、飽和食塩水を用いたエーテル抽出液の洗浄、無水硫酸マグネシウムを用いたエーテル抽出液からの水の除去、エーテル抽出液の濾過及び濾液の減圧濃縮を順に行った後、濃縮された濾液から溶媒を留去して化合物１を得た。ここで、反応液を加熱及び撹拌した時間を反応時間とし、該反応時間を下記表１に示す。
Next, the embodiment will be described more specifically with reference to examples , reference examples, and comparative examples.
(Examples 1 to 7, 12 and 13 , Reference Examples 8 to 11 and Comparative Examples 1 and 2)
In Example 1, 0.500 mmol (114 mg) of N-benzyl-benzenecarbothioamide as a thiocarbonyl compound, 0.100 mmol (9.9 mg) of copper (I) chloride as a catalyst and a polar solvent in a 20 ml two-necked eggplant flask As a reaction solution, 0.5 ml of DMSO was added. Next, after the air in the two-necked eggplant flask was replaced with oxygen, the reaction solution was heated to 80 ° C. and stirred. The progress of the reaction was confirmed by thin layer chromatography (TLC) using a developing solvent with a volume ratio of hexane and ethyl acetate of 5: 1 every time a certain time passed after heating and stirring of the reaction solution. . After the presence of N-benzyl-benzenecarbothioamide as a reaction product could not be confirmed by TLC, ether extraction of the reaction solution using a saturated aqueous ammonium chloride solution and ether was repeated three times to obtain an ether extract. Subsequently, the ether extract was washed with saturated saline, water was removed from the ether extract with anhydrous magnesium sulfate, the ether extract was filtered, and the filtrate was concentrated under reduced pressure. Then, the solvent was distilled off to obtain Compound 1. Here, the time for heating and stirring the reaction solution is defined as the reaction time, and the reaction time is shown in Table 1 below.
実施例２〜７、１２及び１３、並びに参考例８〜１１においては、極性溶媒の種類等を下記表１に示すように変更した以外は、実施例１と同様にして化合物１を得た。ここで、実施例６においては、反応液の加熱温度を９０℃とした。さらに実施例７及び参考例９においては、反応時間を表１に示す時間に設定した。加えて、参考例１０及び１１においては、反応液に配位性化合物としての２，２’−ビピリジンを触媒に対して2モル当量（40mmol、31mg）加え、実施例１２及び１３においては、反応液に２，２’−ビピリジンを触媒に対して1モル当量（20mmol、15.5mg）加えた。 In Examples 2 to 7, 12 and 13 , and Reference Examples 8 to 11 , Compound 1 was obtained in the same manner as Example 1 except that the type of polar solvent was changed as shown in Table 1 below. Here, in Example 6, the heating temperature of the reaction liquid was 90 ° C. Furthermore, in Example 7 and Reference Example 9, the reaction time was set to the time shown in Table 1. In addition, in Reference Examples 10 and 11, 2 molar equivalents (40 mmol, 31 mg) of 2,2′-bipyridine as a coordinating compound was added to the reaction solution with respect to the catalyst, and in Examples 12 and 13, the reaction was performed. To the solution, 2,2′-bipyridine was added at a molar equivalent (20 mmol, 15.5 mg) based on the catalyst.
一方、比較例１及び２においては、極性溶媒の種類や反応時間を表１に示すように変更した以外は、実施例１と同様の反応を行った。 On the other hand, in Comparative Examples 1 and 2, the same reaction as in Example 1 was performed except that the type of polar solvent and the reaction time were changed as shown in Table 1.
（化合物１）
1H-NMR(CDCl3)：δ4.53(d,J=5.85Hz,2H,CH2), 6.85(bs,1H,NH), 7.15-7.50(m,8H,Ar), 7.74-7.77(m,2H,Ar).
以上の結果とN-ベンジル-ベンゼンカルボチオアミドの1H-NMRのスペクトルとを比較す
ることにより、化合物１はカルボニル化合物としてのN-ベンジル-ベンゼンカルボアミド
であると同定した。このため、実施例１〜７、１２及び１３、並びに参考例８〜１１では、下記反応式（３）に示すように、N-ベンジル-ベンゼンカルボチオアミドの脱硫酸素化反応が進行してN-ベンジル-ベンゼンカルボアミドが製造されたことが明らかとなった。また、触媒を塩化パラジウム（ＩＩ）に変更するとともに反応液の加熱温度を１２０℃とした以外は実施例１２と同様の反応を行ったところ、データは示さないが、核磁気共鳴スペクトルの測定により反応物の反応が進行したことを確認した。
(Compound 1)
1H-NMR (CDCl 3 ): δ4.53 (d, J = 5.85 Hz, 2H, CH 2 ), 6.85 (bs, 1H, NH), 7.15-7.50 (m, 8H, Ar), 7.74-7.77 (m , 2H, Ar).
By comparing the above results with the 1H-NMR spectrum of N-benzyl-benzenecarbothioamide, Compound 1 was identified as N-benzyl-benzenecarboxamide as a carbonyl compound. Therefore, in Examples 1 to 7, 12 and 13 and Reference Examples 8 to 11 , as shown in the following reaction formula (3), the desulfurization reaction of N-benzyl-benzenecarbothioamide proceeds and N- It was revealed that benzyl-benzenecarboxamide was produced. Further, when the reaction was carried out in the same manner as in Example 12 except that the catalyst was changed to palladium (II) chloride and the heating temperature of the reaction solution was set to 120 ° C., no data was shown, but the nuclear magnetic resonance spectrum was measured. It was confirmed that the reaction of the reaction product proceeded.
（実施例１４）
実施例１４においては、N-ベンジル-ベンゼンカルボチオアミドを、前記一般式（１）中のＲ1及びＲ2が下記表２に示すものであるチオカルボニル化合物又はセレノカルボニル化合物に変更した以外は、前記実施例１と同様にして化合物２〜１５を得た。各チオカルボニル化合物又は各セレノカルボニル化合物の反応時間を表２に示す。
(Example 14)
In Example 14, N-benzyl-benzenecarbothioamide was changed to a thiocarbonyl compound or a selenocarbonyl compound in which R 1 and R 2 in the general formula (1) are those shown in Table 2 below. In the same manner as in Example 1, compounds 2 to 15 were obtained. Table 2 shows the reaction time of each thiocarbonyl compound or each selenocarbonyl compound.
（化合物２）
1H-NMR(CDCl3)：δ1.17(t,J=7.6Hz,3H,CH3), 2.23(q,J=7.6Hz,2H,CH2), 4.41(d,J=5.37Hz,2H,CH2), 5.98(bs,1H,NH), 7.25-7.34(m,5H,Ar).
以上の結果と反応物であるチオカルボニル化合物の1H-NMRのスペクトルとを比較することにより、化合物２はカルボニル化合物としてのN-(フェニルメチル)-プロパンアミドであると同定した。
（化合物３及び化合物１５）
1H-NMR(CDCl3)：δ3.75(s,3H,CH3), 4.53(d,J=5.37Hz,2H,CH2), 6.42(bs,1H,NH), 6.80-6.83(m,2H,Ar), 7.18-7.26(m,5H,Ar), 7.66-7.70(m,2H,Ar).
以上の結果と反応物であるチオカルボニル化合物又はセレノカルボニル化合物の1H-NMRのスペクトルとを比較することにより、化合物３及び化合物１５はカルボニル化合物としてのN-フェニルメチル 4-メトキシベンゼンカルボアミドであると同定した。
（化合物４）
1H-NMR(CDCl3)：δ1.10(d,J=6.83Hz,6H,CH3), 2.31(sept.,J=6.83Hz,1H,CH), 4.34(d,J=5.37Hz,2H,CH2), 5.81(bs,1H,NH), 7.17-7.27(m,5H,Ar).
以上の結果と反応物であるチオカルボニル化合物の1H-NMRのスペクトルとを比較することにより、化合物４はカルボニル化合物としてのN-(フェニルメチル)-2-メチル-プロパンアミドであると同定した。
（化合物５）
1H-NMR(CDCl3)：δ2.38(s,3H,CH3), 4.61(d,J=5.37Hz,2H,CH2), 6.55(bs,1H,NH), 7.19-7.34(m,7H,Ar), 7.68-7.70(m,2H,Ar).
以上の結果と反応物であるチオカルボニル化合物の1H-NMRのスペクトルとを比較することにより、化合物５はカルボニル化合物としてのN-フェニルメチル 4-メチルベンゼンカルボアミドであると同定した。
（化合物６）
1H-NMR(CDCl3)：δ1.22(s,9H,CH3), 4.41(d,J=5.86Hz,2H,CH2), 6.07(bs,1H,NH), 7.23-7.34(m,5H,Ar).
以上の結果と反応物であるチオカルボニル化合物の1H-NMRのスペクトルとを比較することにより、化合物６はカルボニル化合物としてのN-(フェニルメチル)- 2,2-ジメチル-プロパンアミドであると同定した。
（化合物７）
1H-NMR(CDCl3)：δ4.63(d,J=5.36Hz,2H,CH2), 6.64(bs,1H,NH), 7.29-7.43(m,5H,Ar), 7.59-7.70(m,2H,Ar), 7.82-7.91(m,2H,Ar).
以上の結果と反応物であるチオカルボニル化合物の1H-NMRのスペクトルとを比較することにより、化合物７はカルボニル化合物としてのN-フェニルメチル 4-トリフルオロベンゼンカルボアミドであると同定した。
（化合物８）
1H-NMR(CDCl3)：δ2.08(s,3H,C(=O)Me), 2.94(s,3H, NMe2), 3.03(s,3H,NMe2).
以上の結果と反応物であるチオカルボニル化合物の1H-NMRのスペクトルとを比較することにより、化合物８はカルボニル化合物としてのN,N-ジメチルアセトアミドであると同定した。
（化合物９）
1H-NMR(CDCl3)：δ1.21(t,3H,J=7.31Hz,CH3), 2.45(q,2H,J=7.31Hz,CH2), 4.45(s,2H,CH2Ph中のCH2), 4.61(s,2H,CH2Ph中のCH2), 7.10-7.39(m,10H,Ar).
以上の結果と反応物であるチオカルボニル化合物の1H-NMRのスペクトルとを比較することにより、化合物９はカルボニル化合物としてのN,N-ビス(フェニルメチル)-プロパンアミドであると同定した。
（化合物１０）
1H-NMR(CDCl3)：δ1.11(d,J=6.34Hz,6H,CH3), 2.76(sept.,J=6.83Hz,1H,CH), 4.38(s,2H,CH2), 4.52(s,2H,CH2), 7.01-7.32(m,10H,Ar).
以上の結果と反応物であるチオカルボニル化合物の1H-NMRのスペクトルとを比較することにより、化合物１０はカルボニル化合物としてのN,N-ビス(フェニルメチル)-2-メチル-プロパンアミドであると同定した。
（化合物１１）
1H-NMR(CDCl3)：δ1.28(s,9H,CH3), 4.53(bs,4H,CH2), 7.04-7.26(m,10H,Ar).
以上の結果と反応物であるチオカルボニル化合物の1H-NMRのスペクトルとを比較することにより、化合物１１はカルボニル化合物としてのN,N-ビス(フェニルメチル)-2,2-ジメチル-プロパンアミドであると同定した。
（化合物１２）
1H-NMR(CDCl3)：δ2.79(s,12H,CH3).
以上の結果と反応物であるチオカルボニル化合物の1H-NMRのスペクトルとを比較することにより、化合物１２はカルボニル化合物としてのテトラメチルウレアであると同定した。
（化合物１３）
1H-NMR(CDCl3)：δ0.87(s,6H,CH3), 2.80(s,4H,CH2), 7.37(bs,2H,NH).
以上の結果と反応物であるチオカルボニル化合物の1H-NMRのスペクトルとを比較することにより、化合物１３はカルボニル化合物としてのテトラヒドロ-5,5-ジメチル-2(1H)-ピリミジノンであると同定した。
（化合物１４）
1H-NMR(CDCl3)：δ1.68-1.96(m,4H,NCH2CH2においてNCH2に結合するCH2), 2.38(dt,J=6.7,14.2Hz,1H,PhCHCH2中のCH2), 2.78(dt,J=6.7,14.2Hz,1H,PhCHCH2中のCH2), 3.10-3.20(m,1H,NCH2),3.25-3.52(m,3H,NCH2), 3.55(t,J=7.8Hz,1H,PhCH中のCH), 4.89(d,J=11.2Hz,1H,CH2=CH-中のCH2), 4.95(d,J=17.6Hz,1H,CH2=CH-中のCH2), 5.63-5.73(m,1H,CH2=CH-中のCH), 7.10-7.57(m,5H,Ar).
以上の結果と反応物であるセレノカルボニル化合物の1H-NMRのスペクトルとを比較することにより、化合物１４はカルボニル化合物としての1-(2-フェニル-1-オキソ-4-ペンテニル)ピロリジンであると同定した。このため、実施例１４では、下記反応式（４）に示すように、チオカルボニル化合物の脱硫酸素化反応又はセレノカルボニル化合物の脱セレノ酸素化反応が進行してカルボニル化合物が製造されたことが明らかとなった。尚、下記反応式（４）において、Ｅは硫黄原子又はセレン原子を示す。
(Compound 2)
1 H-NMR (CDCl 3 ): δ 1.17 (t, J = 7.6 Hz, 3H, CH 3 ), 2.23 (q, J = 7.6 Hz, 2H, CH 2 ), 4.41 (d, J = 5.37 Hz, 2H, CH 2), 5.98 ( bs, 1H, NH), 7.25-7.34 (m, 5H, Ar).
By comparing the above results with the 1 H-NMR spectrum of the reactant thiocarbonyl compound, Compound 2 was identified as N- (phenylmethyl) -propanamide as the carbonyl compound.
(Compound 3 and Compound 15)
1 H-NMR (CDCl 3 ): δ3.75 (s, 3H, CH 3 ), 4.53 (d, J = 5.37Hz, 2H, CH 2 ), 6.42 (bs, 1H, NH), 6.80-6.83 (m , 2H, Ar), 7.18-7.26 (m, 5H, Ar), 7.66-7.70 (m, 2H, Ar).
By comparing the above results with the 1 H-NMR spectrum of the thiocarbonyl compound or selenocarbonyl compound as a reaction product, compound 3 and compound 15 are N-phenylmethyl 4-methoxybenzenecarboxamide as the carbonyl compound. Identified.
(Compound 4)
1 H-NMR (CDCl 3 ): δ 1.10 (d, J = 6.83 Hz, 6H, CH 3 ), 2.31 (sept., J = 6.83 Hz, 1H, CH), 4.34 (d, J = 5.37 Hz, 2H, CH 2), 5.81 ( bs, 1H, NH), 7.17-7.27 (m, 5H, Ar).
By comparing the above results with the 1 H-NMR spectrum of the reactant thiocarbonyl compound, compound 4 was identified as N- (phenylmethyl) -2-methyl-propanamide as the carbonyl compound. .
(Compound 5)
1 H-NMR (CDCl 3 ): δ 2.38 (s, 3H, CH 3 ), 4.61 (d, J = 5.37 Hz, 2H, CH 2 ), 6.55 (bs, 1H, NH), 7.19-7.34 (m , 7H, Ar), 7.68-7.70 (m, 2H, Ar).
By comparing the above results with the 1 H-NMR spectrum of the thiocarbonyl compound as the reaction product, Compound 5 was identified as N-phenylmethyl 4-methylbenzenecarboxamide as the carbonyl compound.
(Compound 6)
1 H-NMR (CDCl 3 ): δ1.22 (s, 9H, CH 3 ), 4.41 (d, J = 5.86Hz, 2H, CH 2 ), 6.07 (bs, 1H, NH), 7.23-7.34 (m , 5H, Ar).
By comparing the above results with the 1 H-NMR spectrum of the thiocarbonyl compound as a reaction product, it was found that compound 6 was N- (phenylmethyl) -2,2-dimethyl-propanamide as a carbonyl compound. Identified.
(Compound 7)
1 H-NMR (CDCl 3 ): δ 4.63 (d, J = 5.36 Hz, 2H, CH 2 ), 6.64 (bs, 1H, NH), 7.29-7.43 (m, 5H, Ar), 7.59-7.70 ( m, 2H, Ar), 7.82-7.91 (m, 2H, Ar).
By comparing the above results with the 1 H-NMR spectrum of the thiocarbonyl compound as a reaction product, Compound 7 was identified as N-phenylmethyl 4-trifluorobenzenecarboxamide as a carbonyl compound.
(Compound 8)
1 H-NMR (CDCl 3 ): δ 2.08 (s, 3H, C (= O) Me), 2.94 (s, 3H, NMe 2 ), 3.03 (s, 3H, NMe 2 ).
By comparing the above results with the 1 H-NMR spectrum of the thiocarbonyl compound as a reaction product, Compound 8 was identified as N, N-dimethylacetamide as a carbonyl compound.
(Compound 9)
1 H-NMR (CDCl 3 ): δ 1.21 (t, 3H, J = 7.31Hz, CH 3 ), 2.45 (q, 2H, J = 7.31Hz, CH 2 ), 4.45 (s, 2H, CH 2 Ph CH 2), 4.61 (s, 2H, CH 2 in CH 2 Ph) in, 7.10-7.39 (m, 10H, Ar ).
By comparing the above results with the 1 H-NMR spectrum of the thiocarbonyl compound as a reaction product, Compound 9 was identified as N, N-bis (phenylmethyl) -propanamide as a carbonyl compound.
(Compound 10)
1 H-NMR (CDCl 3 ): δ1.11 (d, J = 6.34Hz, 6H, CH 3 ), 2.76 (sept., J = 6.83Hz, 1H, CH), 4.38 (s, 2H, CH 2 ) , 4.52 (s, 2H, CH 2 ), 7.01-7.32 (m, 10H, Ar).
By comparing the above results with the 1 H-NMR spectrum of the thiocarbonyl compound as a reaction product, compound 10 is N, N-bis (phenylmethyl) -2-methyl-propanamide as a carbonyl compound. Was identified.
(Compound 11)
1 H-NMR (CDCl 3 ): δ 1.28 (s, 9H, CH 3 ), 4.53 (bs, 4H, CH 2 ), 7.04-7.26 (m, 10H, Ar).
By comparing the above results with the 1 H-NMR spectrum of the reaction product thiocarbonyl compound, compound 11 was found to be N, N-bis (phenylmethyl) -2,2-dimethyl-propanamide as a carbonyl compound. Identified.
(Compound 12)
1 H-NMR (CDCl 3 ): δ 2.79 (s, 12H, CH 3 ).
By comparing the above results with the 1 H-NMR spectrum of the thiocarbonyl compound as the reaction product, Compound 12 was identified as tetramethylurea as the carbonyl compound.
(Compound 13)
1 H-NMR (CDCl 3 ): δ 0.87 (s, 6H, CH 3 ), 2.80 (s, 4H, CH 2 ), 7.37 (bs, 2H, NH).
By comparing the above results with the 1 H-NMR spectrum of the reactant thiocarbonyl compound, compound 13 was identified as tetrahydro-5,5-dimethyl-2 (1H) -pyrimidinone as the carbonyl compound. did.
(Compound 14)
1 H-NMR (CDCl 3 ): δ 1.68-1.96 (CH 2 bonded to NCH 2 in m, 4H, NCH 2 CH 2 ), 2.38 (dt, J = 6.7, 14.2 Hz, 1H, in PhCHCH 2 CH 2), 2.78 (dt, J = 6.7,14.2Hz, 1H, CH 2 in PhCHCH 2), 3.10-3.20 (m, 1H, NCH 2), 3.25-3.52 (m, 3H, NCH 2), 3.55 (t, J = 7.8Hz, 1H , CH in PhCH), 4.89 (d, J = 11.2Hz, 1H, CH 2 = CH- CH 2 medium), 4.95 (d, J = 17.6Hz, 1H, CH 2 = CH 2 in CH-), 5.63-5.73 (m, 1H, CH 2 = CH in CH-), 7.10-7.57 (m, 5H, Ar).
By comparing the above results with the 1 H-NMR spectrum of the selenocarbonyl compound as a reaction product, compound 14 is 1- (2-phenyl-1-oxo-4-pentenyl) pyrrolidine as a carbonyl compound. Was identified. For this reason, in Example 14, as shown in the following reaction formula (4), it was clear that the desulfurization reaction of the thiocarbonyl compound or the deselenooxygenation reaction of the selenocarbonyl compound proceeded to produce the carbonyl compound. It became. In the following reaction formula (4), E represents a sulfur atom or a selenium atom.
実施例１５においては、N-ベンジル-ベンゼンカルボチオアミドを下記一般式（５）で示される構造を有する化合物Ａ及び下記一般式（６）で示される構造を有する化合物Ｂの混合物に変更し、さらに反応温度及び反応時間を下記表３に示すように変更した以外は、前記実施例１と同様にして化合物を得た。ここで、前記混合物中の化合物Ａ及び化合物Ｂのモル比は１：１とした。
In Example 15, N-benzyl-benzenecarbothioamide was changed to a mixture of compound A having a structure represented by the following general formula (5) and compound B having a structure represented by the following general formula (6). A compound was obtained in the same manner as in Example 1 except that the reaction temperature and reaction time were changed as shown in Table 3 below. Here, the molar ratio of Compound A and Compound B in the mixture was 1: 1.
実施例１６〜１９においては、N-ベンジル-ベンゼンカルボチオアミド及び反応時間を下記表４に示すように変更した以外は、前記実施例１と同様にして化合物１６〜１９を得た。
In Examples 16 to 19, compounds 16 to 19 were obtained in the same manner as in Example 1 except that N-benzyl-benzenecarbothioamide and the reaction time were changed as shown in Table 4 below.
（化合物１６）
1H-NMR(CDCl3)：δ4.59(d,J=5.37Hz,2H,CH2), 6.61(bs,1H,NH), 7.00-7.11(m,2H,Ar), 7.26-7.43(m,5H,Ar), 7.76-7.80(m,2H,Ar).
以上の結果と反応物であるチオカルボニル化合物の1H-NMRのスペクトルとを比較することにより、化合物１６はカルボニル化合物としてのN-フェニルメチル 4-フルオロベンゼンカルボアミドであると同定した。
（化合物１７）
1H-NMR(CDCl3)：δ2.43(s,3H), 7.27(d,J=7.9Hz,2H), 8.01(d,J=7.9Hz,2H).
ms=136
以上の結果と反応物であるチオカルボニル化合物の1H-NMRのスペクトル及びマススペクトルとを比較することにより、化合物１７はカルボニル化合物としての４−メチル安息香酸フェニルであると同定した。
（化合物１８）
ms=221
以上の結果と反応物であるチオカルボニル化合物のマススペクトルを比較することにより、化合物１８はカルボニル化合物としてのN-ベンゾイルカルバミン酸ブチルであると同定した。
（化合物１９）
ms=237
以上の結果と反応物であるチオカルボニル化合物のマススペクトルのスペクトルとを比較することにより、化合物１９はカルボニル化合物としてのN-ベンゾイルチオカルバミン酸ブチルであると同定した。このため、実施例１６〜１９では、チオカルボニル化合物の脱硫酸素化反応が進行してカルボニル化合物がそれぞれ製造されたことが明らかとなった。
(Compound 16)
1 H-NMR (CDCl 3 ): δ 4.59 (d, J = 5.37 Hz, 2H, CH 2 ), 6.61 (bs, 1H, NH), 7.00-7.11 (m, 2H, Ar), 7.26-7.43 ( m, 5H, Ar), 7.76-7.80 (m, 2H, Ar).
By comparing the above results with the 1 H-NMR spectrum of the thiocarbonyl compound as a reaction product, Compound 16 was identified as N-phenylmethyl 4-fluorobenzenecarboxamide as a carbonyl compound.
(Compound 17)
1 H-NMR (CDCl 3 ): δ 2.43 (s, 3H), 7.27 (d, J = 7.9 Hz, 2H), 8.01 (d, J = 7.9 Hz, 2H).
ms = 136
By comparing the above results with the 1 H-NMR spectrum and mass spectrum of the thiocarbonyl compound as a reaction product, the compound 17 was identified as phenyl 4-methylbenzoate as the carbonyl compound.
(Compound 18)
ms = 221
By comparing the above results with the mass spectrum of the thiocarbonyl compound as a reaction product, Compound 18 was identified as butyl N-benzoylcarbamate as the carbonyl compound.
(Compound 19)
ms = 237
By comparing the above results with the spectrum of the mass spectrum of the reactant thiocarbonyl compound, it was identified that compound 19 was butyl N-benzoylthiocarbamate as the carbonyl compound. For this reason, in Examples 16-19, it became clear that the desulfurization reaction of the thiocarbonyl compound proceeded to produce the carbonyl compound.
なお、本実施形態は、次のように変更して具体化することも可能である。
・ 前記分子状酸素の反応液への溶解を、空気雰囲気下で反応液を静置若しくは撹拌する、又は反応液中に空気を通気することにより行ってもよい。このように構成した場合には、空気中の酸素が反応液に溶解する。さらに、分子状酸素を反応液に溶解させる前に、該反応液の脱気を行ってもよい。加えて、反応液に分子状酸素を溶解させるときに、酸素ガスや空気を加圧してもよい。
In addition, this embodiment can also be changed and embodied as follows.
The molecular oxygen may be dissolved in the reaction solution by allowing the reaction solution to stand or stir in an air atmosphere or venting air through the reaction solution. When configured in this manner, oxygen in the air dissolves in the reaction solution. Further, before the molecular oxygen is dissolved in the reaction solution, the reaction solution may be degassed. In addition, oxygen gas or air may be pressurized when molecular oxygen is dissolved in the reaction solution.
・ カルボニル基中の酸素の質量数が１６のカルボニル化合物から公知の方法によりチオカルボニル化合物又はセレノカルボニル化合物を得た後、質量数が１７又は１８の酸素同位体で構成される分子状酸素を用いてカルボニル化合物を製造してもよい。このとき、製造されたカルボニル化合物は、カルボニル基中の酸素の質量数が１７又は１８である。質量数が１７の酸素原子はＮＭＲ活性を有し、質量数が１８の酸素原子は質量数が１６のそれに次いで天然存在比が高く入手が容易である。 ・ After obtaining a thiocarbonyl compound or selenocarbonyl compound from a carbonyl compound having a mass number of oxygen of 16 in the carbonyl group by a known method, molecular oxygen composed of an oxygen isotope having a mass number of 17 or 18 is used. Thus, a carbonyl compound may be produced. At this time, the produced carbonyl compound has a mass number of oxygen in the carbonyl group of 17 or 18. An oxygen atom having a mass number of 17 has NMR activity, and an oxygen atom having a mass number of 18 has a natural abundance ratio next to that of a mass number of 16, and is readily available.
ここで、生体内における生理活性物質とその受容体（レセプター）との相互作用や代謝過程は、一般的に生体内の受容体に対して特定の元素をその安定同位体に置換したゲスト分子を作用させることにより解明される。生理活性物質は、その多くがカルボニル基を有しているために、ゲスト分子にはカルボニル化合物が一般的に用いられる。 Here, interactions and metabolic processes between physiologically active substances and their receptors (receptors) in vivo are generally based on guest molecules in which specific elements are substituted with stable isotopes for receptors in the living body. Elucidated by acting. Since many physiologically active substances have a carbonyl group, a carbonyl compound is generally used as a guest molecule.
従来、カルボニル化合物の同位体ラベル化は、質量数が１７又は１８の酸素同位体を含有する重水にカルボニル化合物を加えて加熱することにより行われる。このとき、重水中の酸素同位体は、カルボニル化合物中の酸素との交換反応によりカルボニル化合物に導入される。カルボニル化合物中の酸素と重水中の酸素同位体との交換反応は可逆的に進行する。このため、酸素同位体がカルボニル化合物に導入される割合、即ち酸素同位体のカルボニル化合物への導入率は前記交換反応の化学平衡に起因して例えば２０％程度と低く、同位体の導入率が高いゲスト分子の製造は困難であった。ここで、カルボニル化合物に対して大過剰の重水を用いることにより酸素同位体のカルボニル化合物への導入率をある程度高めることはできるものの、大過剰の重水を用いることによるゲスト分子の製造コストの増大等の弊害の埋め合わせにはならない。 Conventionally, isotope labeling of a carbonyl compound is performed by adding the carbonyl compound to heavy water containing an oxygen isotope having a mass number of 17 or 18 and heating. At this time, the oxygen isotope in heavy water is introduced into the carbonyl compound by an exchange reaction with oxygen in the carbonyl compound. The exchange reaction between oxygen in the carbonyl compound and oxygen isotope in heavy water proceeds reversibly. For this reason, the rate at which the oxygen isotope is introduced into the carbonyl compound, that is, the introduction rate of the oxygen isotope into the carbonyl compound is, for example, as low as about 20% due to the chemical equilibrium of the exchange reaction. Production of high guest molecules has been difficult. Here, the introduction rate of oxygen isotopes into the carbonyl compound can be increased to some extent by using a large excess of heavy water relative to the carbonyl compound, but the production cost of the guest molecule is increased by using a large excess of heavy water, etc. It does not make up for the evils of
これに対し、実施形態の脱硫酸素化反応及び脱セレノ酸素化反応は不可逆的に進行する。このため、実施形態のカルボニル化合物の製造方法は、カルボニル化合物に対して大過剰の重水を用いることなく、酸素同位体のカルボニル化合物への導入率を容易に高めることができる。このため、実施形態のカルボニル化合物の製造方法を用いることにより、同位体の導入率が高いゲスト分子を容易に製造することができる。 In contrast, the desulfurization reaction and the deseleno oxygenation reaction of the embodiment proceed irreversibly. For this reason, the method for producing a carbonyl compound of the embodiment can easily increase the introduction rate of the oxygen isotope into the carbonyl compound without using a large excess of heavy water relative to the carbonyl compound. Therefore, by using the method for producing a carbonyl compound of the embodiment, a guest molecule having a high isotope introduction rate can be easily produced.
さらに、前記実施形態より把握できる技術的思想について以下に記載する。 Further, the technical idea that can be grasped from the embodiment will be described below .
・ 前記極性溶媒がジメチルホルムアミド又はジメチルスルホキシドである請求項１から請求項３のいずれか一項に記載のカルボニル化合物の製造方法。この構成によれば、カルボニル化合物の製造効率を高めることができる。 The method for producing a carbonyl compound according to any one of claims 1 to 3, wherein the polar solvent is dimethylformamide or dimethyl sulfoxide. According to this configuration, the production efficiency of the carbonyl compound can be increased.
・ 前記極性溶媒に配位性化合物が配合されることを特徴とする請求項１から請求項３のいずれか一項に記載のカルボニル化合物の製造方法。この構成によれば、チオカルボニル化合物又はセレノカルボニル化合物と分子状酸素との反応を促進することができる。 The method for producing a carbonyl compound according to any one of claims 1 to 3, wherein a coordinating compound is blended in the polar solvent. According to this configuration, the reaction between the thiocarbonyl compound or the selenocarbonyl compound and molecular oxygen can be promoted.
・ 前記反応の反応温度が５０〜８０℃であることを特徴とする請求項１から請求項３のいずれか一項に記載のカルボニル化合物の製造方法。この構成によれば、カルボニル化合物の製造効率を高めることができる。 -The reaction temperature of the said reaction is 50-80 degreeC, The manufacturing method of the carbonyl compound as described in any one of Claims 1-3 characterized by the above-mentioned. According to this configuration, the production efficiency of the carbonyl compound can be increased.
Claims (3)
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