JPH05255204A - Production of amines - Google Patents
Production of aminesInfo
- Publication number
- JPH05255204A JPH05255204A JP4052265A JP5226592A JPH05255204A JP H05255204 A JPH05255204 A JP H05255204A JP 4052265 A JP4052265 A JP 4052265A JP 5226592 A JP5226592 A JP 5226592A JP H05255204 A JPH05255204 A JP H05255204A
- Authority
- JP
- Japan
- Prior art keywords
- reaction
- group
- catalyst
- substituted
- raw material
- 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.)
- Pending
Links
- 150000001412 amines Chemical class 0.000 title abstract description 15
- 238000004519 manufacturing process Methods 0.000 title description 6
- 239000003054 catalyst Substances 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 125000003277 amino group Chemical group 0.000 claims abstract description 6
- 125000003118 aryl group Chemical group 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 19
- 239000007858 starting material Substances 0.000 claims description 11
- 238000006114 decarboxylation reaction Methods 0.000 claims description 9
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 abstract description 21
- 239000002994 raw material Substances 0.000 abstract description 6
- 150000001413 amino acids Chemical class 0.000 abstract description 4
- 150000002576 ketones Chemical class 0.000 abstract description 4
- 230000003287 optical effect Effects 0.000 abstract description 3
- 239000002253 acid Substances 0.000 abstract description 2
- 150000001735 carboxylic acids Chemical class 0.000 abstract description 2
- 230000001766 physiological effect Effects 0.000 abstract description 2
- 238000000746 purification Methods 0.000 abstract description 2
- NTPLXRHDUXRPNE-UHFFFAOYSA-N 4-methoxyacetophenone Chemical compound COC1=CC=C(C(C)=O)C=C1 NTPLXRHDUXRPNE-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- -1 aryl ketones Chemical class 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 7
- JHHZLHWJQPUNKB-SCSAIBSYSA-N (3r)-pyrrolidin-3-ol Chemical compound O[C@@H]1CCNC1 JHHZLHWJQPUNKB-SCSAIBSYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 5
- 238000009776 industrial production Methods 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- GNKZMNRKLCTJAY-UHFFFAOYSA-N 4'-Methylacetophenone Chemical compound CC(=O)C1=CC=C(C)C=C1 GNKZMNRKLCTJAY-UHFFFAOYSA-N 0.000 description 4
- IQZLUWLMQNGTIW-UHFFFAOYSA-N acetoveratrone Chemical compound COC1=CC=C(C(C)=O)C=C1OC IQZLUWLMQNGTIW-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- GPRYKVSEZCQIHD-UHFFFAOYSA-N 1-(4-aminophenyl)ethanone Chemical compound CC(=O)C1=CC=C(N)C=C1 GPRYKVSEZCQIHD-UHFFFAOYSA-N 0.000 description 2
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- BBMCTIGTTCKYKF-UHFFFAOYSA-N 1-heptanol Chemical compound CCCCCCCO BBMCTIGTTCKYKF-UHFFFAOYSA-N 0.000 description 2
- YXWWHNCQZBVZPV-UHFFFAOYSA-N 2'-methylacetophenone Chemical compound CC(=O)C1=CC=CC=C1C YXWWHNCQZBVZPV-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 235000008206 alpha-amino acids Nutrition 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- 229960002433 cysteine Drugs 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- 229960002885 histidine Drugs 0.000 description 2
- UCUUFSAXZMGPGH-UHFFFAOYSA-N penta-1,4-dien-3-one Chemical class C=CC(=O)C=C UCUUFSAXZMGPGH-UHFFFAOYSA-N 0.000 description 2
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical compound CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 229960002898 threonine Drugs 0.000 description 2
- HXKKHQJGJAFBHI-GSVOUGTGSA-N (2R)-1-aminopropan-2-ol Chemical compound C[C@@H](O)CN HXKKHQJGJAFBHI-GSVOUGTGSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- KEIFWROAQVVDBN-UHFFFAOYSA-N 1,2-dihydronaphthalene Chemical compound C1=CC=C2C=CCCC2=C1 KEIFWROAQVVDBN-UHFFFAOYSA-N 0.000 description 1
- FODUVZQSLRHUMC-UHFFFAOYSA-N 1-(2,3-dimethoxyphenyl)ethanone Chemical compound COC1=CC=CC(C(C)=O)=C1OC FODUVZQSLRHUMC-UHFFFAOYSA-N 0.000 description 1
- HSDSKVWQTONQBJ-UHFFFAOYSA-N 1-(2,4-dimethylphenyl)ethanone Chemical compound CC(=O)C1=CC=C(C)C=C1C HSDSKVWQTONQBJ-UHFFFAOYSA-N 0.000 description 1
- WPRAXAOJIODQJR-UHFFFAOYSA-N 1-(3,4-dimethylphenyl)ethanone Chemical compound CC(=O)C1=CC=C(C)C(C)=C1 WPRAXAOJIODQJR-UHFFFAOYSA-N 0.000 description 1
- BUZYGTVTZYSBCU-UHFFFAOYSA-N 1-(4-chlorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Cl)C=C1 BUZYGTVTZYSBCU-UHFFFAOYSA-N 0.000 description 1
- VQTDPCRSXHFMOL-UHFFFAOYSA-N 2,4-Dimethoxyacetophenone Chemical compound COC1=CC=C(C(C)=O)C(OC)=C1 VQTDPCRSXHFMOL-UHFFFAOYSA-N 0.000 description 1
- CKQHAYFOPRIUOM-UHFFFAOYSA-N 3'-Aminoacetophenone Chemical compound CC(=O)C1=CC=CC(N)=C1 CKQHAYFOPRIUOM-UHFFFAOYSA-N 0.000 description 1
- LJCWONGJFPCTTL-UHFFFAOYSA-N 4-hydroxyphenylglycine Chemical compound OC(=O)C(N)C1=CC=C(O)C=C1 LJCWONGJFPCTTL-UHFFFAOYSA-N 0.000 description 1
- YQYGPGKTNQNXMH-UHFFFAOYSA-N 4-nitroacetophenone Chemical compound CC(=O)C1=CC=C([N+]([O-])=O)C=C1 YQYGPGKTNQNXMH-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000004983 alkyl aryl ketones Chemical class 0.000 description 1
- 150000001371 alpha-amino acids Chemical class 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 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
- FFSAXUULYPJSKH-UHFFFAOYSA-N butyrophenone Chemical compound CCCC(=O)C1=CC=CC=C1 FFSAXUULYPJSKH-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- QCRFMSUKWRQZEM-UHFFFAOYSA-N cycloheptanol Chemical compound OC1CCCCCC1 QCRFMSUKWRQZEM-UHFFFAOYSA-N 0.000 description 1
- CGZZMOTZOONQIA-UHFFFAOYSA-N cycloheptanone Chemical compound O=C1CCCCCC1 CGZZMOTZOONQIA-UHFFFAOYSA-N 0.000 description 1
- 125000005805 dimethoxy phenyl group Chemical group 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 235000014304 histidine Nutrition 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- PFPYHYZFFJJQFD-UHFFFAOYSA-N oxalic anhydride Chemical compound O=C1OC1=O PFPYHYZFFJJQFD-UHFFFAOYSA-N 0.000 description 1
- NODGRWCMFMEGJH-UHFFFAOYSA-N p-ethylacetophenone Chemical compound CCC1=CC=C(C(C)=O)C=C1 NODGRWCMFMEGJH-UHFFFAOYSA-N 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229960001153 serine Drugs 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229960004441 tyrosine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【0001】[0001]
【産業上の利用分野】本発明はアミノ基を有するカルボ
ン酸類の脱炭酸により、アミン類を製造する方法に関す
る。FIELD OF THE INVENTION The present invention relates to a method for producing amines by decarboxylation of carboxylic acids having an amino group.
【0002】アミン類は多様な生理活性を有し、工業原
料としても重要である。とくに側鎖に種々の官能基を有
するものや光学活性なアミン類は、医薬、農薬などの原
料として近年著しくその重要性を増してきている。Amines have various physiological activities and are important as industrial raw materials. Particularly, those having various functional groups in the side chains and optically active amines have been remarkably increasing in importance as raw materials for medicines, agricultural chemicals and the like in recent years.
【0003】本発明の製造法によれば、前記のごとき有
用なアミン類を天然に多量に存在し、入手が容易なアミ
ノ酸などを原料として、低コストで容易に製造すること
ができる。According to the production method of the present invention, the useful amines as described above are naturally present in a large amount and can be easily produced at a low cost using easily available amino acids and the like as raw materials.
【0004】[0004]
【従来の技術および発明が解決しようとする課題】一般
に、化合物の脱炭酸反応は強加熱することにより行なわ
れるが、特定の脱炭酸しやすい構造を有する化合物を除
いて、かなり高温、長時間の苛酷な条件を必要とするば
あいが多い。これを回避するために過酸化物、銅塩など
の触媒存在下に反応を行なっている例もあるが、これら
の触媒はその危険性、廃棄物処理などの点で工業生産上
望ましくない(薬学雑誌,85巻,1965年,531 頁、米国
特許第4262157 号明細書)。2. Description of the Related Art Generally, the decarboxylation reaction of a compound is carried out by heating strongly. However, except for a compound having a specific structure which is easily decarboxylated, it is heated at a considerably high temperature for a long time. In many cases, harsh conditions are required. In order to avoid this, there are some examples where the reaction is carried out in the presence of a catalyst such as a peroxide or a copper salt, but these catalysts are not desirable in industrial production in terms of their danger, waste disposal, etc. Magazine, 85, 1965, page 531, U.S. Pat. No. 4,262,157).
【0005】これらの問題点に対し、特開昭60-23328号
公報に記載された方法は取扱いが容易でかつ反応の後処
理も簡便なビニルケトン類を触媒として用いる工業生産
上非常に有用な方法であるが、触媒として用いるビニル
ケトン類が工業生産規模での入手が困難であったり、安
定性がよくないという別の問題がある。In order to solve these problems, the method described in JP-A-60-23328 is a very useful method for industrial production in which vinyl ketones are used as catalysts because they are easy to handle and the post-treatment of the reaction is simple. However, there are other problems that it is difficult to obtain vinyl ketones used as a catalyst on an industrial production scale, and the stability is not good.
【0006】本発明者らは以上のような問題点を解決す
るため鋭意検討を行なった結果、安価で工業生産規模で
も安定に入手でき、かつ安定性においても優れたアリー
ルケトン類が脱炭酸反応の触媒として有用であり、この
触媒を用いることにより収率よくアミン類を製造しうる
ことを見出し、本発明を完成するに至った。As a result of intensive studies to solve the above problems, the present inventors have found that the decarboxylation reaction of aryl ketones, which is inexpensive, can be stably obtained even on an industrial production scale, and is excellent in stability. It was found that the present invention is useful as a catalyst for the above, and that amines can be produced in good yield by using this catalyst, and has completed the present invention.
【0007】[0007]
【課題を解決するための手段】本発明は、アミノ基を有
するカルボン酸類を出発原料として用い、一般式(I):The present invention uses a carboxylic acid having an amino group as a starting material and has the general formula (I):
【0008】[0008]
【化2】 [Chemical 2]
【0009】(式中、R1 は置換または無置換のアリー
ル基を示し、R2 は置換または無置換のアルキル基を示
し、R1 とR2 とは結合して環を形成していてもよい)
で表わされるモノアリールケトン触媒存在下に脱炭酸反
応を行なうことを特徴とするアミン類の製造法に関す
る。(In the formula, R 1 represents a substituted or unsubstituted aryl group, R 2 represents a substituted or unsubstituted alkyl group, and R 1 and R 2 may be bonded to each other to form a ring. Good)
The present invention relates to a method for producing amines, which comprises carrying out a decarboxylation reaction in the presence of a monoarylketone catalyst.
【0010】[0010]
【作用および実施例】本発明の製造法によれば、出発原
料が効果的に脱炭酸反応を起こして目的のアミン類とな
る。前記出発原料としては、アミノ基を有するカルボン
酸類であればとくに制限なく使用しうる。出発原料の具
体例としては、たとえばグリシン、アラニン、フェニル
アラニン、ロイシン、イソロイシン、バリン、フェニル
グリシンなどのアルキルまたはアリール側鎖を有するα
- アミノ酸類をはじめとして、スレオニン、セリン、チ
ロシン、p- ヒドロキシフェニルグリシン、アスパラギ
ン、アスパラギン酸、グルタミン酸、リジン、アルギニ
ン、ヒスチジン、オルニチン、トリプトファン、システ
イン、シスチンなどの側鎖にヒドロキシル基、カルボキ
シル基、塩基性官能基、硫黄を含む官能基などを有する
α- アミノ酸類や、プロリン、ヒドロキシプロリンなど
の環式α- アミノ酸類などがとくに望ましいものとして
あげられ、さらにこれらの誘導体やその他の置換基を有
する化合物を使用してもよい。ACTIONS AND EXAMPLES According to the production method of the present invention, the starting material effectively undergoes a decarboxylation reaction to obtain the desired amines. As the starting material, any carboxylic acid having an amino group may be used without particular limitation. Specific examples of the starting material include α having an alkyl or aryl side chain such as glycine, alanine, phenylalanine, leucine, isoleucine, valine, and phenylglycine.
-Including amino acids, threonine, serine, tyrosine, p-hydroxyphenylglycine, asparagine, aspartic acid, glutamic acid, lysine, arginine, histidine, ornithine, tryptophan, cysteine, cysteine, side chain hydroxyl group, carboxyl group, Α-Amino acids having a basic functional group, a functional group containing sulfur, etc., and cyclic α-amino acids such as proline and hydroxyproline are particularly preferable. Further, derivatives of these and other substituents may be used. You may use the compound which has.
【0011】前記出発原料は立体異性体、たとえば光学
異性体であってもなんら反応に影響を与えることがない
ばかりでなく、もとの立体配置を保持したまま反応が進
行し、光学活性なアミン類をうることができる。Even if the starting material is a stereoisomer, for example, an optical isomer, it does not affect the reaction at all, and the reaction proceeds while maintaining the original configuration, resulting in an optically active amine. You can get the kind.
【0012】本発明で触媒として用いられるアリールケ
トン類は、一般式(I) :The aryl ketones used as a catalyst in the present invention have the general formula (I):
【0013】[0013]
【化3】 [Chemical 3]
【0014】(式中、R1 は置換または無置換のアリー
ル基を示し、R2 は置換または無置換のアルキル基を示
し、R1 とR2 とは結合して環を形成していてもよい)
で表わされるモノアリールケトンである。(In the formula, R 1 represents a substituted or unsubstituted aryl group, R 2 represents a substituted or unsubstituted alkyl group, and R 1 and R 2 may be bonded to each other to form a ring. Good)
It is a monoaryl ketone represented by.
【0015】前記R1 としては、たとえばフェニル基;
少なくとも1つのアルキル基、好ましくは炭素数1〜4
のアルキル基、アルコキシ基、好ましくは炭素数1〜4
のアルコキシ基、アミノ基、ニトロ基、ハロゲン原子な
どで置換された置換フェニル基などがあげられる。な
お、置換フェニル基は置換基の位置がo- 位、m- 位、
p- 位(2,3,4,5,6)またはそれらの組合せの
位置のものを任意に選ぶことができる。R1 の具体例と
しては、たとえばメチルフェニル基、エチルフェニル
基、ジメチルフェニル基、メトキシフェニル基、ジメト
キシフェニル基、クロロフェニル基、アミノフェニル
基、ニトロフェニル基などがあげられる。Examples of R 1 include a phenyl group;
At least one alkyl group, preferably 1 to 4 carbon atoms
Alkyl group, alkoxy group, preferably having 1 to 4 carbon atoms
And an alkoxy group, an amino group, a nitro group, a substituted phenyl group substituted with a halogen atom, and the like. In the substituted phenyl group, the position of the substituent is o-position, m-position,
The p-position (2, 3, 4, 5, 6) or a combination thereof can be arbitrarily selected. Specific examples of R 1 include a methylphenyl group, an ethylphenyl group, a dimethylphenyl group, a methoxyphenyl group, a dimethoxyphenyl group, a chlorophenyl group, an aminophenyl group and a nitrophenyl group.
【0016】前記R2 としては、たとえば炭素数1〜5
のアルキル基があげられ、その具体例としては、たとえ
ばメチル基、エチル基、プロピル基、ブチル基などがあ
げられる。The R 2 is, for example, 1 to 5 carbon atoms.
And alkyl groups, and specific examples thereof include a methyl group, an ethyl group, a propyl group and a butyl group.
【0017】R1 とR2 とが結合して環状を形成するば
あいも、一般式(I) におけるR1 、R2 が結合して環を
形成する基からとくに限定することなく選ばれる。When R 1 and R 2 are combined to form a ring, they are selected from groups in which R 1 and R 2 in the general formula (I) are combined to form a ring without particular limitation.
【0018】一般式(I) で表わされるモノアリールケト
ンの具体例としては、たとえばアセトフェノン、プロピ
オフェノン、ブチロフェノンなどのアルキルアリールケ
トン類、p- メチルアセトフェノン、o- メチルアセト
フェノン、p- エチルアセトフェノン、2,4-ジメチルア
セトフェノン、3,4-ジメチルアセトフェノン、p- メト
キシアセトフェノン、3,4-ジメトキシアセトフェノン、
2,4-ジメトキシアセトフェノン、2,3-ジメトキシアセト
フェノン、p- クロロアセトフェノン、p- アミノアセ
トフェノン、p- ニトロアセトフェノンなどのような置
換または無置換の一般に置換アリールケトン類と呼ばれ
る化合物群や、α- テトラロンなどの環状のアリールケ
トン類があげられるが、これらに限定されるものではな
い。Specific examples of the monoaryl ketone represented by the general formula (I) include alkyl aryl ketones such as acetophenone, propiophenone and butyrophenone, p-methylacetophenone, o-methylacetophenone, p-ethylacetophenone, 2,4-dimethylacetophenone, 3,4-dimethylacetophenone, p-methoxyacetophenone, 3,4-dimethoxyacetophenone,
Substituted or unsubstituted compounds such as 2,4-dimethoxyacetophenone, 2,3-dimethoxyacetophenone, p-chloroacetophenone, p-aminoacetophenone and p-nitroacetophenone, which are generally called substituted aryl ketones, and α- Examples thereof include, but are not limited to, cyclic aryl ketones such as tetralone.
【0019】前記触媒の使用量は精製のしやすさの点か
ら出発原料に対して1〜20モル%が好ましく、3〜10モ
ル%がさらに好ましい。The amount of the catalyst used is preferably 1 to 20 mol% and more preferably 3 to 10 mol% with respect to the starting material from the viewpoint of easy purification.
【0020】本発明における脱炭酸反応は無溶媒で行な
ってもよいが、反応を均一に進めやすい、反応温度をコ
ントロールしやすいなどの理由から、出発原料、反応生
成物の溶解度を考慮して適当な溶媒の存在下に行なうほ
うが好ましい。前記溶媒としては、反応に関与しない不
活性溶媒であればとくに限定なく使用することができ
る。その具体例としては、たとえばオクタノール、ヘプ
タノール、ヘキサノール、シクロヘキサノール、シクロ
ヘプタノールなどのアルコール類、テトラリン、オクタ
リン、ジヒドロナフタレンなどの炭化水素類、シクロヘ
キサノン、シクロヘプタノンなどのケトン類などがあげ
られるが、反応温度、収率などの点からアルコール類が
好ましい。The decarboxylation reaction in the present invention may be carried out in the absence of a solvent, but it is suitable considering the solubility of the starting materials and the reaction product for the reasons that the reaction can proceed uniformly and the reaction temperature can be easily controlled. It is preferable to carry out in the presence of a different solvent. As the solvent, any inert solvent that does not participate in the reaction can be used without particular limitation. Specific examples thereof include alcohols such as octanol, heptanol, hexanol, cyclohexanol, and cycloheptanol, hydrocarbons such as tetralin, octaline, and dihydronaphthalene, and ketones such as cyclohexanone and cycloheptanone. Alcohols are preferable in terms of reaction temperature, yield, and the like.
【0021】本発明における脱炭酸反応では、出発原
料、触媒および適宜使用される溶媒を仕込んだのち、原
料や溶媒によって選択される適当な温度条件下、好まし
くはチッ素気流下で出発原料が消費されるまで撹拌し、
反応を完結させることが好ましい。In the decarboxylation reaction of the present invention, after the starting material, the catalyst and the solvent used as appropriate are charged, the starting material is consumed under a suitable temperature condition selected depending on the material and the solvent, preferably under a nitrogen stream. Stir until
It is preferable to complete the reaction.
【0022】反応温度は100 〜250 ℃程度の任意の温度
が選択されるが、工業生産上140 〜170 ℃付近が好まし
い。The reaction temperature may be selected at an arbitrary temperature of about 100 to 250 ° C, but is preferably about 140 to 170 ° C in industrial production.
【0023】前記の適切な条件を選択することにより反
応は高率で進行し、高収率で目的のアミン類が合成され
るため、反応後目的のアミン類を容易に単離しうる。た
とえば適当な酸の塩として結晶化させる、蒸留する、貧
溶媒を用いてそのまま結晶化させるなどの方法により純
度の高いものが取得され、必要なばあいはカラムクロマ
トグラフィー、再結晶などの方法により精製を行なえば
よい。By selecting the appropriate conditions described above, the reaction proceeds at a high rate and the desired amines are synthesized in a high yield, so that the desired amines can be easily isolated after the reaction. For example, a highly pure product is obtained by a method such as crystallization as an appropriate acid salt, distillation, or crystallization as it is using a poor solvent. If necessary, column chromatography, recrystallization or the like is used. It may be purified.
【0024】つぎに実施例をあげて本発明をさらに詳細
に具体的に説明するが、本発明はこれらの実施例に限定
されるものではない。Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.
【0025】実施例1(3-(R)-ヒドロキシピロリジンの
合成) 4-(R)-ヒドロキシ- L- プロリン100 g、p- メチルア
セトフェノン10gおよびシクロヘキサノール500 mlを加
えた懸濁液を150 〜160 ℃付近でチッ素気流下激しく撹
拌した。2時間後結晶が消失して均一になった反応溶液
を室温付近まで冷却し、トルエン500 mlを加え、さらに
5℃まで冷却した。この溶液に内温が15℃以上にならな
いように注意しながら乾燥した塩化水素ガスを吹き込む
と結晶が析出した。えられたスラリー液を5℃で1時間
撹拌を続けたのち、結晶をグラスフィルターで濾取し
た。えられた結晶をトルエン500 mlで洗浄し、真空乾燥
器で乾燥すると目的化合物が塩酸塩として81.5gえられ
た(収率86%)。Example 1 (Synthesis of 3- (R) -hydroxypyrrolidine) 100 g of 4- (R) -hydroxy-L-proline, 10 g of p-methylacetophenone and 500 ml of cyclohexanol were added to give a suspension of 150. The mixture was vigorously stirred under a nitrogen stream at about 160 ° C. After 2 hours, the reaction solution in which crystals disappeared and became uniform was cooled to around room temperature, 500 ml of toluene was added, and further cooled to 5 ° C. When dry hydrogen chloride gas was blown into this solution while being careful not to let the internal temperature rise above 15 ° C, crystals were precipitated. After stirring the obtained slurry liquid at 5 ° C. for 1 hour, the crystals were collected by filtration with a glass filter. The obtained crystals were washed with 500 ml of toluene and dried in a vacuum drier to obtain 81.5 g of the desired compound as a hydrochloride salt (yield 86%).
【0026】このものの光学純度をHPLCにより測定する
ことにより3位の立体配置はRであり、この反応におい
て出発原料の絶対配置が保たれ、ラセミ化が起こってい
ないことを確認した。えられた化合物のNMR スペクト
ル、融点および比旋光度を以下に示す。By measuring the optical purity of this product by HPLC, it was confirmed that the configuration at the 3-position was R, the absolute configuration of the starting material was maintained in this reaction, and racemization did not occur. The NMR spectrum, melting point and specific rotation of the obtained compound are shown below.
【0027】n.m.r.(d6 -DMSO,90MHz ) δ(ppm ):1.8-1.9 (2H,m)、3.0-3.3 (4H,m)、4.
4 (1H,m)、7.0-8.0 (2H,broad) m.p. 109-110 ℃Nmr (d 6 -DMSO, 90MHz) δ (ppm): 1.8-1.9 (2H, m), 3.0-3.3 (4H, m), 4.
4 (1H, m), 7.0-8.0 (2H, broad) mp 109-110 ℃
【0028】[0028]
【数1】 [Equation 1]
【0029】実施例2(3-(R)-ヒドロキシピロリジンの
合成) 4-(R)-ヒドロキシ- L- プロリン5g、p- メトキシア
セトフェノン270 mgおよびシクロヘキサノール25mlを加
えた懸濁液を150 〜160 ℃付近でチッ素気流下激しく撹
拌した。2時間後結晶が消失して均一になった反応溶液
を、実施例1と同様の操作で処理することにより、目的
化合物が塩酸塩として4.1 gえられた(収率87%)。え
られた化合物は実施例1と同様にして確認した。Example 2 (Synthesis of 3- (R) -hydroxypyrrolidine) A suspension containing 150 g of 4- (R) -hydroxy-L-proline, 270 mg of p-methoxyacetophenone and 25 ml of cyclohexanol was added. The mixture was vigorously stirred under a nitrogen stream at around 160 ° C. After 2 hours, the reaction solution in which the crystals disappeared and became uniform was treated in the same manner as in Example 1 to obtain 4.1 g of the desired compound as a hydrochloride (yield 87%). The obtained compound was confirmed in the same manner as in Example 1.
【0030】実施例3(3-(R)-ヒドロキシピロリジンの
合成) p- メトキシアセトフェノンのかわりに3,4-ジメトキシ
アセトフェノン340 mgを加え、実施例2と同様の操作を
行なうことにより、目的化合物が塩酸塩として4.0 gえ
られた(収率85%)。えられた化合物は実施例1と同様
にして確認した。Example 3 (Synthesis of 3- (R) -hydroxypyrrolidine) In place of p-methoxyacetophenone, 340 mg of 3,4-dimethoxyacetophenone was added and the same procedure as in Example 2 was carried out to obtain the desired compound. Was obtained as a hydrochloride (yield 85%). The obtained compound was confirmed in the same manner as in Example 1.
【0031】実施例4(3-(R)-ヒドロキシピロリジンの
合成) p- メトキシアセトフェノンのかわりにプロピオフェノ
ン260 mgを加え、実施例2と同様の操作を行なうことに
より、目的化合物が塩酸塩として3.8 gえられた(収率
81%)。えられた化合物は実施例1と同様にして確認し
た。Example 4 (Synthesis of 3- (R) -hydroxypyrrolidine) Propiophenone (260 mg) was added instead of p-methoxyacetophenone, and the same procedure as in Example 2 was carried out to give the target compound as a hydrochloride salt. As 3.8 g (yield
81%). The obtained compound was confirmed in the same manner as in Example 1.
【0032】実施例5(3-(R)-ヒドロキシピロリジンの
合成) p- メトキシアセトフェノンのかわりにα- テトラロン
550 mgを加え、実施例2と同様の操作を行なうことによ
り、目的化合物が塩酸塩として4.3 gえられた(収率91
%)。えられた化合物は実施例1と同様にして確認し
た。Example 5 (Synthesis of 3- (R) -hydroxypyrrolidine) α-tetralone instead of p-methoxyacetophenone
By adding 550 mg and performing the same operation as in Example 2, 4.3 g of the target compound was obtained as a hydrochloride (yield 91
%). The obtained compound was confirmed in the same manner as in Example 1.
【0033】実施例6(3-(R)-ヒドロキシピロリジンの
合成) p- メトキシアセトフェノンのかわりに3-アミノアセト
フェノンまたは4-アミノアセトフェノン260 mgを加え、
実施例2と同様の操作を行なうことにより、いずれも目
的化合物が塩酸塩として4.0 gえられた(収率85%)。
えられた化合物はそれぞれ実施例1と同様にして確認し
た。Example 6 (Synthesis of 3- (R) -hydroxypyrrolidine) 260 mg of 3-aminoacetophenone or 4-aminoacetophenone was added instead of p-methoxyacetophenone,
By carrying out the same operation as in Example 2, 4.0 g of the target compound was obtained as a hydrochloride in each case (yield 85%).
The obtained compounds were confirmed in the same manner as in Example 1.
【0034】実施例7(1-アミノ-2-(R)- プロパノール
の合成) L- スレオニン10gおよびα- テトラロン1.28gにシク
ロヘキサノール50mlを加えた懸濁液を150 〜160 ℃付近
でチッ素気流下激しく撹拌した。4時間後結晶が消失し
て均一になった反応溶液を50℃付近まで冷却し、酢酸エ
チル100 mlに溶解させた無水シュウ酸8.0 gを添加し
た。えられたスラリーを室温まで冷却し1時間撹拌した
のち、グラスフィルターで濾取し、酢酸エチル50mlで2
回洗浄した。えられた結晶を真空ポンプで50℃、5時間
乾燥することにより、目的化合物の重シュウ酸塩13.04
gをえた(収率94%)。えられたもののNMR スペクト
ル、融点および比旋光度を以下に示す。Example 7 (Synthesis of 1-amino-2- (R) -propanol) A suspension of 10 g of L-threonine and 1.28 g of α-tetralone with 50 ml of cyclohexanol was added at about 150 to 160 ° C. Stir vigorously under a stream of air. After 4 hours, the reaction solution in which the crystals disappeared and became uniform was cooled to around 50 ° C., and 8.0 g of oxalic anhydride dissolved in 100 ml of ethyl acetate was added. The resulting slurry was cooled to room temperature and stirred for 1 hour, then filtered through a glass filter and washed with 2 × 50 ml of ethyl acetate.
Washed twice. The obtained crystals are dried at 50 ° C for 5 hours with a vacuum pump to give the target compound, a heavy oxalate salt of 13.04.
g was obtained (94% yield). The NMR spectrum, melting point and specific rotation of the obtained product are shown below.
【0035】n.m.r.(d6 -DMSO,90MHz ) δ(ppm ):1.1 (3H,d)、2.6 (1H,dd )、2.8 (1
H,dd )、3.8 (1H,m)、7.9-8.3 (1H,broad) m.p. 138-140 ℃Nmr (d 6 -DMSO, 90MHz) δ (ppm): 1.1 (3H, d), 2.6 (1H, dd), 2.8 (1
H, dd), 3.8 (1H, m), 7.9-8.3 (1H, broad) mp 138-140 ℃
【0036】[0036]
【数2】 [Equation 2]
【0037】実施例8(ヒスタミンの合成) L- ヒスチジン25.4gおよびα- テトラロン2.35gに、
シクロヘキサノール125 mlを加えた懸濁液を150 〜160
℃付近でチッ素気流下激しく撹拌した。1日加熱撹拌を
続けたのち結晶が消失して均一になった反応溶液を室温
付近まで冷却し、トルエン250 mlを加え、10℃に冷却し
ながら塩酸ガス12.0gを吹き込んだ。ついでスラリー化
した溶液を冷却したまま1時間撹拌したのち、グラスフ
ィルターで濾取し、トルエン20mlで3回洗浄し、真空ポ
ンプで40℃、6時間乾燥することにより、目的化合物2
8.3gをえた(収率94%)。えられた化合物のNMR スペ
クトルおよび融点を以下に示す。Example 8 (Synthesis of Histamine) To 25.4 g of L-histidine and 2.35 g of α-tetralone,
Add a suspension containing 125 ml of cyclohexanol to 150-160.
The mixture was vigorously stirred under a nitrogen stream at around ℃. After continuing heating and stirring for 1 day, the reaction solution in which crystals disappeared and became uniform was cooled to around room temperature, 250 ml of toluene was added, and 12.0 g of hydrochloric acid gas was blown in while cooling to 10 ° C. Then, the slurried solution was stirred for 1 hour while being cooled, filtered by a glass filter, washed 3 times with 20 ml of toluene, and dried by a vacuum pump at 40 ° C. for 6 hours to obtain the target compound 2
8.3 g was obtained (yield 94%). The NMR spectrum and melting point of the obtained compound are shown below.
【0038】n.m.r.(d6 -DMSO,90MHz ) δ(ppm ):3.1-3.7 (4H,d)、7.5 (1H,d)、8.8
(1H,d) m.p. 252-254 ℃Nmr (d 6 -DMSO, 90MHz) δ (ppm): 3.1-3.7 (4H, d), 7.5 (1H, d), 8.8
(1H, d) mp 252-254 ℃
【0039】[0039]
【発明の効果】本発明の製造法によれば、天然に多量に
存在し、入手が容易なアミノ酸などから脱炭酸反応によ
り容易にアミン類を製造しうる。EFFECTS OF THE INVENTION According to the production method of the present invention, amines can be easily produced by decarboxylation reaction from amino acids and the like which are naturally present in large amounts and are easily available.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.5 識別記号 庁内整理番号 FI 技術表示箇所 C07D 207/12 7019−4C 233/64 105 // C07B 61/00 300 ─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 5 Identification code Office reference number FI technical display location C07D 207/12 7019-4C 233/64 105 // C07B 61/00 300
Claims (1)
料として用い、一般式(I) : 【化1】 (式中、R1 は置換または無置換のアリール基を示し、
R2 は置換または無置換のアルキル基を示し、R1 とR
2 とは結合して環を形成していてもよい)で表わされる
モノアリールケトン触媒存在下に脱炭酸反応を行なうこ
とを特徴とするアミン類の製造法。1. Using a carboxylic acid having an amino group as a starting material, the compound represented by the general formula (I): (In the formula, R 1 represents a substituted or unsubstituted aryl group,
R 2 represents a substituted or unsubstituted alkyl group, and R 1 and R
(2 may combine with each other to form a ring), and the decarboxylation reaction is carried out in the presence of a monoarylketone catalyst.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP4052265A JPH05255204A (en) | 1992-03-11 | 1992-03-11 | Production of amines |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP4052265A JPH05255204A (en) | 1992-03-11 | 1992-03-11 | Production of amines |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH05255204A true JPH05255204A (en) | 1993-10-05 |
Family
ID=12909943
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP4052265A Pending JPH05255204A (en) | 1992-03-11 | 1992-03-11 | Production of amines |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH05255204A (en) |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0692471A1 (en) | 1994-07-15 | 1996-01-17 | Degussa Aktiengesellschaft | Process for the preparation of optically active 3-hydroxypyrrolidine derivatives with high optical purity |
WO1997043256A1 (en) * | 1996-05-14 | 1997-11-20 | Kyowa Hakko Kogyo Co., Ltd. | Process for the preparation of 3-hydroxypyrrolidine |
WO2000039098A1 (en) * | 1998-12-23 | 2000-07-06 | Maxim Pharmaceuticals, Inc. | Synthesis of histamine dihydrochloride |
JP2001220372A (en) * | 2000-02-09 | 2001-08-14 | Toray Ind Inc | Method for producing amines |
CN1315780C (en) * | 1994-10-27 | 2007-05-16 | 住友化学株式会社 | Process for producing n-(1-(2,4-dichlorophenyl)ethyl)-2- cyano-3,3-dimethylbutanamide |
US7223873B2 (en) | 2004-03-30 | 2007-05-29 | Daisco Co., Ltd | Process for preparing amines |
US7652152B2 (en) | 2005-07-20 | 2010-01-26 | Chiroad Incorporate | Synthetic method of optically pure (S)-3-hydroxypyrrolidine |
CN103739552A (en) * | 2014-01-24 | 2014-04-23 | 国药一心制药有限公司 | Preparation method of histamine dihydrochloride |
CN104402825A (en) * | 2014-12-13 | 2015-03-11 | 济南诚汇双达化工有限公司 | Histamine dihydrochloride synthesis method |
EP4382529A1 (en) | 2022-12-07 | 2024-06-12 | Bayer Consumer Care AG | A process for preparing pure (3s)-pyrrolidin-3-ol and pure (3s)-pyrrolidin-3-ol hydrochloride |
-
1992
- 1992-03-11 JP JP4052265A patent/JPH05255204A/en active Pending
Cited By (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0692471A1 (en) | 1994-07-15 | 1996-01-17 | Degussa Aktiengesellschaft | Process for the preparation of optically active 3-hydroxypyrrolidine derivatives with high optical purity |
CN1315780C (en) * | 1994-10-27 | 2007-05-16 | 住友化学株式会社 | Process for producing n-(1-(2,4-dichlorophenyl)ethyl)-2- cyano-3,3-dimethylbutanamide |
WO1997043256A1 (en) * | 1996-05-14 | 1997-11-20 | Kyowa Hakko Kogyo Co., Ltd. | Process for the preparation of 3-hydroxypyrrolidine |
WO2000039098A1 (en) * | 1998-12-23 | 2000-07-06 | Maxim Pharmaceuticals, Inc. | Synthesis of histamine dihydrochloride |
US6403806B1 (en) | 1998-12-23 | 2002-06-11 | Maxim Pharmaceuticals, Inc. | Synthesis of histamine dihydrochloride |
US6528654B2 (en) | 1998-12-23 | 2003-03-04 | Maxim Pharmaceuticals, Inc. | Synthesis of histamine dihydrochloride |
US6620942B2 (en) | 1998-12-23 | 2003-09-16 | Maxim Pharmaceuticals | Synthesis of histamine dihydrochloride |
JP2001220372A (en) * | 2000-02-09 | 2001-08-14 | Toray Ind Inc | Method for producing amines |
JP4665185B2 (en) * | 2000-02-09 | 2011-04-06 | 東レ・ファインケミカル株式会社 | Production method of amines |
US7223873B2 (en) | 2004-03-30 | 2007-05-29 | Daisco Co., Ltd | Process for preparing amines |
US7652152B2 (en) | 2005-07-20 | 2010-01-26 | Chiroad Incorporate | Synthetic method of optically pure (S)-3-hydroxypyrrolidine |
CN103739552A (en) * | 2014-01-24 | 2014-04-23 | 国药一心制药有限公司 | Preparation method of histamine dihydrochloride |
CN104402825A (en) * | 2014-12-13 | 2015-03-11 | 济南诚汇双达化工有限公司 | Histamine dihydrochloride synthesis method |
EP4382529A1 (en) | 2022-12-07 | 2024-06-12 | Bayer Consumer Care AG | A process for preparing pure (3s)-pyrrolidin-3-ol and pure (3s)-pyrrolidin-3-ol hydrochloride |
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