KR20020043512A - Preparation of Nitroalkenes - Google Patents
Preparation of Nitroalkenes Download PDFInfo
- Publication number
- KR20020043512A KR20020043512A KR1020020025969A KR20020025969A KR20020043512A KR 20020043512 A KR20020043512 A KR 20020043512A KR 1020020025969 A KR1020020025969 A KR 1020020025969A KR 20020025969 A KR20020025969 A KR 20020025969A KR 20020043512 A KR20020043512 A KR 20020043512A
- Authority
- KR
- South Korea
- Prior art keywords
- nitro
- vinyl
- benzene
- group
- yield
- 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.)
- Ceased
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 51
- 238000000034 method Methods 0.000 claims abstract description 55
- -1 Nitro alkene derivatives Chemical class 0.000 claims description 69
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000004185 ester group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 6
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 84
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 48
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 48
- 238000003756 stirring Methods 0.000 description 17
- 239000003480 eluent Substances 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 238000010898 silica gel chromatography Methods 0.000 description 12
- 239000000203 mixture Substances 0.000 description 10
- CTJKRKMPTRJAIT-AATRIKPKSA-N 4-[(e)-2-nitroethenyl]phenol Chemical compound OC1=CC=C(\C=C\[N+]([O-])=O)C=C1 CTJKRKMPTRJAIT-AATRIKPKSA-N 0.000 description 8
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 7
- 239000012141 concentrate Substances 0.000 description 6
- 238000004821 distillation Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- PIAOLBVUVDXHHL-VOTSOKGWSA-N β-nitrostyrene Chemical class [O-][N+](=O)\C=C\C1=CC=CC=C1 PIAOLBVUVDXHHL-VOTSOKGWSA-N 0.000 description 5
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- VTIIJXUACCWYHX-UHFFFAOYSA-L disodium;carboxylatooxy carbonate Chemical compound [Na+].[Na+].[O-]C(=O)OOC([O-])=O VTIIJXUACCWYHX-UHFFFAOYSA-L 0.000 description 4
- 238000009509 drug development Methods 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 4
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 229940045872 sodium percarbonate Drugs 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QDRLNSJTMBNERI-SNAWJCMRSA-N 1,2-dichloro-3-[(e)-2-nitroethenyl]benzene Chemical compound [O-][N+](=O)\C=C\C1=CC=CC(Cl)=C1Cl QDRLNSJTMBNERI-SNAWJCMRSA-N 0.000 description 3
- OFJZSDMKKDTNHZ-VOTSOKGWSA-N 1,2-dimethoxy-3-[(e)-2-nitroethenyl]benzene Chemical compound COC1=CC=CC(\C=C\[N+]([O-])=O)=C1OC OFJZSDMKKDTNHZ-VOTSOKGWSA-N 0.000 description 3
- SYJMYDMKPSZMSB-AATRIKPKSA-N 1,2-dimethoxy-4-[(e)-2-nitroethenyl]benzene Chemical compound COC1=CC=C(\C=C\[N+]([O-])=O)C=C1OC SYJMYDMKPSZMSB-AATRIKPKSA-N 0.000 description 3
- IRRZIWHEPWPPJF-AATRIKPKSA-N 1,4-dimethoxy-2-[(e)-2-nitroethenyl]benzene Chemical compound COC1=CC=C(OC)C(\C=C\[N+]([O-])=O)=C1 IRRZIWHEPWPPJF-AATRIKPKSA-N 0.000 description 3
- XFBMDILDMJAPDU-UHFFFAOYSA-N 1-(2-nitroethenyl)-3-phenylmethoxybenzene Chemical compound [O-][N+](=O)C=CC1=CC=CC(OCC=2C=CC=CC=2)=C1 XFBMDILDMJAPDU-UHFFFAOYSA-N 0.000 description 3
- PNCOIHRUXGOUFA-UHFFFAOYSA-N 1-(2-nitroethenyl)-4-phenylbenzene Chemical group C1=CC(C=C[N+](=O)[O-])=CC=C1C1=CC=CC=C1 PNCOIHRUXGOUFA-UHFFFAOYSA-N 0.000 description 3
- MSDHJAWQEZOXGV-UHFFFAOYSA-N 1-(2-nitroethenyl)-4-phenylmethoxybenzene Chemical compound C1=CC(C=C[N+](=O)[O-])=CC=C1OCC1=CC=CC=C1 MSDHJAWQEZOXGV-UHFFFAOYSA-N 0.000 description 3
- JKQUXSHVQGBODD-VOTSOKGWSA-N 1-(4-Methoxyphenyl)-2-nitroethylene Chemical compound COC1=CC=C(\C=C\[N+]([O-])=O)C=C1 JKQUXSHVQGBODD-VOTSOKGWSA-N 0.000 description 3
- PLOZMGIWCWVROY-BQYQJAHWSA-N 1-[(e)-2-nitroethenyl]-4-propan-2-ylbenzene Chemical compound CC(C)C1=CC=C(\C=C\[N+]([O-])=O)C=C1 PLOZMGIWCWVROY-BQYQJAHWSA-N 0.000 description 3
- HNRGHIXNKWOUEO-CMDGGOBGSA-N 1-[(e)-2-nitroethenyl]naphthalene Chemical compound C1=CC=C2C(/C=C/[N+](=O)[O-])=CC=CC2=C1 HNRGHIXNKWOUEO-CMDGGOBGSA-N 0.000 description 3
- GLJATYFHELDGEA-WAYWQWQTSA-N 1-chloro-4-[(z)-2-nitroethenyl]benzene Chemical compound [O-][N+](=O)\C=C/C1=CC=C(Cl)C=C1 GLJATYFHELDGEA-WAYWQWQTSA-N 0.000 description 3
- IZWSBQRAUOSJFM-UHFFFAOYSA-N 1-ethyl-4-(2-nitroethenyl)benzene Chemical compound CCC1=CC=C(C=C[N+]([O-])=O)C=C1 IZWSBQRAUOSJFM-UHFFFAOYSA-N 0.000 description 3
- NKZSNHAEWKEFNE-AATRIKPKSA-N 1-fluoro-2-[(e)-2-nitroethenyl]benzene Chemical compound [O-][N+](=O)\C=C\C1=CC=CC=C1F NKZSNHAEWKEFNE-AATRIKPKSA-N 0.000 description 3
- NOXNBNYWEWJUTM-SNAWJCMRSA-N 1-fluoro-3-[(e)-2-nitroethenyl]benzene Chemical compound [O-][N+](=O)\C=C\C1=CC=CC(F)=C1 NOXNBNYWEWJUTM-SNAWJCMRSA-N 0.000 description 3
- FVKSRNVYJXQCLK-VOTSOKGWSA-N 1-methoxy-2-[(e)-2-nitroethenyl]benzene Chemical compound COC1=CC=CC=C1\C=C\[N+]([O-])=O FVKSRNVYJXQCLK-VOTSOKGWSA-N 0.000 description 3
- IJBGIPFDIABTKB-AATRIKPKSA-N 1-methoxy-3-[(e)-2-nitroethenyl]benzene Chemical compound COC1=CC=CC(\C=C\[N+]([O-])=O)=C1 IJBGIPFDIABTKB-AATRIKPKSA-N 0.000 description 3
- JNMKPRLNICRRIV-UHFFFAOYSA-N 1-methoxy-4-(2-nitroethenyl)-2-phenylmethoxybenzene Chemical compound COC1=CC=C(C=C[N+]([O-])=O)C=C1OCC1=CC=CC=C1 JNMKPRLNICRRIV-UHFFFAOYSA-N 0.000 description 3
- LMSZTOUHOKERPN-UHFFFAOYSA-N 1-methylsulfanyl-4-(2-nitroethenyl)benzene Chemical compound CSC1=CC=C(C=C[N+]([O-])=O)C=C1 LMSZTOUHOKERPN-UHFFFAOYSA-N 0.000 description 3
- FSQRAMKGHLSZCT-BQYQJAHWSA-N 2-[(e)-2-nitroethenyl]naphthalene Chemical compound C1=CC=CC2=CC(/C=C/[N+](=O)[O-])=CC=C21 FSQRAMKGHLSZCT-BQYQJAHWSA-N 0.000 description 3
- SHMGYOIWHNKMNU-UHFFFAOYSA-N 2-bromo-1-methoxy-4-(2-nitroethenyl)benzene Chemical compound COC1=CC=C(C=C[N+]([O-])=O)C=C1Br SHMGYOIWHNKMNU-UHFFFAOYSA-N 0.000 description 3
- ARGNGGCUTGQKIA-UHFFFAOYSA-N 3-methyl-1-nitrobut-1-ene Chemical compound CC(C)C=C[N+]([O-])=O ARGNGGCUTGQKIA-UHFFFAOYSA-N 0.000 description 3
- KFLWBZPSJQPRDD-UHFFFAOYSA-N 5-(2-nitroethenyl)-1,3-benzodioxole Chemical compound [O-][N+](=O)C=CC1=CC=C2OCOC2=C1 KFLWBZPSJQPRDD-UHFFFAOYSA-N 0.000 description 3
- GYOMWYPUMGJROJ-MDZDMXLPSA-N 9-[(e)-2-nitroethenyl]anthracene Chemical compound C1=CC=C2C(/C=C/[N+](=O)[O-])=C(C=CC=C3)C3=CC2=C1 GYOMWYPUMGJROJ-MDZDMXLPSA-N 0.000 description 3
- 239000005695 Ammonium acetate Substances 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229940043376 ammonium acetate Drugs 0.000 description 3
- 235000019257 ammonium acetate Nutrition 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- XHGCFWXSHIHYFH-ONEGZZNKSA-N 1,2-dichloro-4-[(e)-2-nitroethenyl]benzene Chemical compound [O-][N+](=O)\C=C\C1=CC=C(Cl)C(Cl)=C1 XHGCFWXSHIHYFH-ONEGZZNKSA-N 0.000 description 2
- VRFIBLDYVWFPPY-UHFFFAOYSA-N 1,3-dichloro-5-[3-(2-nitroethenyl)phenoxy]benzene Chemical compound [O-][N+](=O)C=CC1=CC=CC(OC=2C=C(Cl)C=C(Cl)C=2)=C1 VRFIBLDYVWFPPY-UHFFFAOYSA-N 0.000 description 2
- SQPQKZLZYZFJBK-UHFFFAOYSA-N 1-(2-nitroethenyl)-2-phenylmethoxybenzene Chemical compound [O-][N+](=O)C=CC1=CC=CC=C1OCC1=CC=CC=C1 SQPQKZLZYZFJBK-UHFFFAOYSA-N 0.000 description 2
- HOATZZMHBCWHOJ-VOTSOKGWSA-N 1-methyl-2-[(e)-2-nitroethenyl]benzene Chemical compound CC1=CC=CC=C1\C=C\[N+]([O-])=O HOATZZMHBCWHOJ-VOTSOKGWSA-N 0.000 description 2
- JSPNBERPFLONRX-VOTSOKGWSA-N 1-methyl-4-[(e)-2-nitroethenyl]benzene Chemical compound CC1=CC=C(\C=C\[N+]([O-])=O)C=C1 JSPNBERPFLONRX-VOTSOKGWSA-N 0.000 description 2
- JIVGSHFYXPRRSZ-UHFFFAOYSA-N 2,3-dimethoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1OC JIVGSHFYXPRRSZ-UHFFFAOYSA-N 0.000 description 2
- PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 2
- 239000001431 2-methylbenzaldehyde Substances 0.000 description 2
- WPHUUIODWRNJLO-UHFFFAOYSA-N 2-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=CC=C1S(Cl)(=O)=O WPHUUIODWRNJLO-UHFFFAOYSA-N 0.000 description 2
- ZWUSBSHBFFPRNE-UHFFFAOYSA-N 3,4-dichlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1Cl ZWUSBSHBFFPRNE-UHFFFAOYSA-N 0.000 description 2
- WMPDAIZRQDCGFH-UHFFFAOYSA-N 3-methoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1 WMPDAIZRQDCGFH-UHFFFAOYSA-N 0.000 description 2
- ZVTWZSXLLMNMQC-UHFFFAOYSA-N 4-phenylmethoxybenzaldehyde Chemical compound C1=CC(C=O)=CC=C1OCC1=CC=CC=C1 ZVTWZSXLLMNMQC-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- WTWBUQJHJGUZCY-UHFFFAOYSA-N cuminaldehyde Chemical compound CC(C)C1=CC=C(C=O)C=C1 WTWBUQJHJGUZCY-UHFFFAOYSA-N 0.000 description 2
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- BTFQKIATRPGRBS-UHFFFAOYSA-N o-tolualdehyde Chemical compound CC1=CC=CC=C1C=O BTFQKIATRPGRBS-UHFFFAOYSA-N 0.000 description 2
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- LLMLNAVBOAMOEE-UHFFFAOYSA-N 2,3-dichlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1Cl LLMLNAVBOAMOEE-UHFFFAOYSA-N 0.000 description 1
- AFUKNJHPZAVHGQ-UHFFFAOYSA-N 2,5-dimethoxy-Benzaldehyde Chemical compound COC1=CC=C(OC)C(C=O)=C1 AFUKNJHPZAVHGQ-UHFFFAOYSA-N 0.000 description 1
- ZWDVQMVZZYIAHO-UHFFFAOYSA-N 2-fluorobenzaldehyde Chemical compound FC1=CC=CC=C1C=O ZWDVQMVZZYIAHO-UHFFFAOYSA-N 0.000 description 1
- PBEJTRAJWCNHRS-UHFFFAOYSA-N 2-phenylmethoxybenzaldehyde Chemical compound O=CC1=CC=CC=C1OCC1=CC=CC=C1 PBEJTRAJWCNHRS-UHFFFAOYSA-N 0.000 description 1
- QMPNFQLVIGPNEI-UHFFFAOYSA-N 3-bromo-4-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1Br QMPNFQLVIGPNEI-UHFFFAOYSA-N 0.000 description 1
- PIKNVEVCWAAOMJ-UHFFFAOYSA-N 3-fluorobenzaldehyde Chemical compound FC1=CC=CC(C=O)=C1 PIKNVEVCWAAOMJ-UHFFFAOYSA-N 0.000 description 1
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
- VQVQZFHUXRSRBZ-UHFFFAOYSA-N 4-methoxy-3-phenylmethoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1OCC1=CC=CC=C1 VQVQZFHUXRSRBZ-UHFFFAOYSA-N 0.000 description 1
- PIMQQGJMDMAZGT-UHFFFAOYSA-N 4-methylthiobenzaldehyde Chemical compound CC1=CC=C(C=S)C=C1 PIMQQGJMDMAZGT-UHFFFAOYSA-N 0.000 description 1
- ISDBWOPVZKNQDW-UHFFFAOYSA-N 4-phenylbenzaldehyde Chemical compound C1=CC(C=O)=CC=C1C1=CC=CC=C1 ISDBWOPVZKNQDW-UHFFFAOYSA-N 0.000 description 1
- FGXZWMCBNMMYPL-UHFFFAOYSA-N 4-propoxybenzaldehyde Chemical compound CCCOC1=CC=C(C=O)C=C1 FGXZWMCBNMMYPL-UHFFFAOYSA-N 0.000 description 1
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- GBAPRSGLWUEXIR-UHFFFAOYSA-N nitromethanol Chemical compound OC[N+]([O-])=O GBAPRSGLWUEXIR-UHFFFAOYSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- SATCULPHIDQDRE-UHFFFAOYSA-N piperonal Chemical compound O=CC1=CC=C2OCOC2=C1 SATCULPHIDQDRE-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- WJUFSDZVCOTFON-UHFFFAOYSA-N veratraldehyde Chemical compound COC1=CC=C(C=O)C=C1OC WJUFSDZVCOTFON-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/01—Compounds containing nitro groups bound to a carbon skeleton having nitro groups bound to acyclic carbon atoms
- C07C205/03—Compounds containing nitro groups bound to a carbon skeleton having nitro groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
- C07C205/04—Compounds containing nitro groups bound to a carbon skeleton having nitro groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
본 발명은 하기 화학식 1-4 와 같이 니트로알켄 유도체의 제법에 관한 것으로, 제조방법 1, 2, 3, 4, 5, 6 의 방법으로 쉽게 합성할 수 있다.The present invention relates to a method for preparing nitroalkene derivatives as in the following Chemical Formula 1-4, and can be easily synthesized by the methods of Preparation Methods 1, 2, 3, 4, 5 and 6.
[화학식 1][Formula 1]
(상기식에서 R 은 명세서에 정의한 바와 같다)(Wherein R is as defined in the specification)
[화학식 2][Formula 2]
(상기식에서 R 은 명세서에 정의한 바와 같다)(Wherein R is as defined in the specification)
[화학식 3][Formula 3]
(상기식에서 R 은 명세서에 정의한 바와 같다)(Wherein R is as defined in the specification)
[화학식 4][Formula 4]
(상기식에서 R 은 명세서에 정의한 바와 같다)(Wherein R is as defined in the specification)
Description
본 발명은 신약개발에서 유용하게 사용 가능한 한단계 반응으로 니트로 알켄(nitro alkene) 유도체를 합성하는 제법에 관한 것이다.The present invention relates to a method for synthesizing nitro alkene derivatives in one step reaction that can be usefully used in drug development.
새로운 니트로알켄 타입의 화합물을 합성하기 위하여는 반응식 1 과 같이 우선 방향족 알데하이드에 염기 촉매를 사용하여 중간체인 니트로알콜을 만든 후 축합과정을 통하여 컨쥬게이션된 니트로알켄이 생성된다.In order to synthesize a new nitroalkene type compound, as shown in Scheme 1, a nitroalcohol, an intermediate, is prepared using a base catalyst on an aromatic aldehyde, and then a condensed nitroalkene is produced through condensation.
이 때 사용되는 시약으로는 수산화나트륨(Organic syntheses, Coll Vol. 1,pp. 413-414), 암모니움 아세테이트(Tetrahedron Letters, Vol. 38, No. 29, pp. 5131-5134, 1997) 등이 사용되어진다. 또한 사용되어 지는 방법은 벤젠링에 치환된 물질에 따라서 제한적으로 반응이 진행되어지기 때문에 여러 가지 유도체를 만들기에는 많은 한계점이 있다. 따라서, 본 발명은 이러한 한계점을 극복하여 어떠한 치환체를 가지고 있는 물질이라도 쉽게 합성할 수 있기 때문에 신약개발에서 유용하게 사용가능한 다양한 컨쥬게이션이 된β-니트로 스틸렌 유도체를 합성하는 것이다.Reagents used in this case include sodium hydroxide (Organic syntheses, Coll Vol. 1, pp. 413-414), ammonium acetate (Tetrahedron Letters, Vol. 38, No. 29, pp. 5131-5134, 1997), and the like. It is used. In addition, the method used has a number of limitations in making various derivatives because the reaction proceeds in a limited manner depending on the substance substituted in the benzene ring. Therefore, the present invention overcomes these limitations and can easily synthesize a substance having any substituent, thereby synthesizing β -nitro styrene derivatives having various conjugated properties that can be usefully used in drug development.
[반응식 1]Scheme 1
본 발명의 목적은 니트로알켄 유도체 화합물을 보다 경제적이고 효과적으로 제조하는 방법을 제공하는 것이다.It is an object of the present invention to provide a method for producing a nitroalkene derivative compound more economically and effectively.
본 발명에서는 신약개발에서 유용하게 여러 가지 저해제로 사용 가능한 니트로알켄 타입의 화합물 유도체의 제조방법을 제공한다.The present invention provides a method for preparing a nitroalkene type compound derivative that can be usefully used as various inhibitors in drug development.
[화학식 1][Formula 1]
상기 화학식 1 에서 사용되어지는 R 기는 수소, 히드록시기, 측쇄 알킬기, 직쇄 알킬기, 할로겐, 메톡시, 펜옥시, 벤질옥시, 에톡시, 프로폭시, 설포닐기, 에스테르기 중 1 종 이상 선택된 치환기가 선택되어질 수 있다.R group used in the formula (1) is selected from at least one substituent selected from hydrogen, hydroxy group, branched alkyl group, linear alkyl group, halogen, methoxy, phenoxy, benzyloxy, ethoxy, propoxy, sulfonyl group, ester group Can be.
[화학식 2][Formula 2]
상기 화학식 2 에서 사용되어지는 R 기는 수소, 히드록시기, 측쇄 알킬기, 직쇄 알킬기, 할로겐, 메톡시, 펜옥시, 벤질옥시, 에톡시, 프로폭시, 설포닐기, 에스테르기 중 1 종 이상 선택된 치환기가 선택되어질 수 있다.The R group used in Formula 2 may be selected from at least one substituent selected from hydrogen, hydroxy group, branched alkyl group, straight chain alkyl group, halogen, methoxy, phenoxy, benzyloxy, ethoxy, propoxy, sulfonyl group and ester group. Can be.
[화학식 3][Formula 3]
상기 화학식 3 에서 사용되어지는 R 기는 수소, 히드록시기, 측쇄 알킬기, 직쇄 알킬기, 할로겐, 메톡시, 펜옥시, 벤질옥시, 에톡시, 프로폭시, 설포닐기, 에스테르기 중 1 종 이상 선택된 치환기가 선택되어질 수 있다.The R group used in Formula 3 may be selected from at least one substituent selected from hydrogen, hydroxy group, branched alkyl group, straight chain alkyl group, halogen, methoxy, phenoxy, benzyloxy, ethoxy, propoxy, sulfonyl group and ester group. Can be.
[화학식 4][Formula 4]
상기 화학식 4 에서 사용되어지는 R 기는 수소, 히드록시기, 측쇄 알킬기, 직쇄 알킬기, 할로겐, 메톡시, 펜옥시, 벤질옥시, 에톡시, 프로폭시, 설포닐기, 에스테르기 중 1종 이상 선택된 치환기가 선택되어질 수 있다.R group used in the above formula (4) is selected from at least one substituent selected from hydrogen, hydroxy group, branched alkyl group, linear alkyl group, halogen, methoxy, phenoxy, benzyloxy, ethoxy, propoxy, sulfonyl group, ester group Can be.
본 발명의 대표적인 화합물 중에는 다음과 같은 물질이 있다.Representative compounds of the present invention include the following substances.
1) (2-니트로-비닐)-벤젠1) (2-nitro-vinyl) -benzene
2) 1-(3,5-디클로로펜옥시)-3-(2-니트로-비닐)-벤젠2) 1- (3,5-dichlorophenoxy) -3- (2-nitro-vinyl) -benzene
3) 1,2-디메톡시-3-(2-니트로-비닐)-벤젠3) 1,2-dimethoxy-3- (2-nitro-vinyl) -benzene
4) 1,4-디메톡시-2-(2-니트로-비닐)-벤젠4) 1,4-dimethoxy-2- (2-nitro-vinyl) -benzene
5) 1,2-디메톡시-4-(2-니트로-비닐)-벤젠5) 1,2-dimethoxy-4- (2-nitro-vinyl) -benzene
6) 1-메톡시-4-(2-니트로-비닐)-벤젠6) 1-methoxy-4- (2-nitro-vinyl) -benzene
7) 1-메톡시-2-(2-니트로-비닐)-벤젠7) 1-methoxy-2- (2-nitro-vinyl) -benzene
8) 1-플로로-3-(2-니트로-비닐)-벤젠8) 1-fluoro-3- (2-nitro-vinyl) -benzene
9) 1-벤질옥시-4-(2-니트로-비닐)-벤젠9) 1-benzyloxy-4- (2-nitro-vinyl) -benzene
10) 1-에틸-4-(2-니트로-비닐)-벤젠10) 1-ethyl-4- (2-nitro-vinyl) -benzene
11) 1-프로폭시-4-(2-니트로-비닐)-벤젠11) 1-propoxy-4- (2-nitro-vinyl) -benzene
12) 1-메톡시-3-(2-니트로-비닐)-벤젠12) 1-methoxy-3- (2-nitro-vinyl) -benzene
13) 1-메톡시-8-(2-니트로-비닐)-나프탈렌13) 1-methoxy-8- (2-nitro-vinyl) -naphthalene
14) 9-(2-니트로-비닐)-안트라센14) 9- (2-nitro-vinyl) -anthracene
15) 1-이소프로필-4-(2-니트로-비닐)-벤젠15) 1-isopropyl-4- (2-nitro-vinyl) -benzene
16) 1-(2-니트로-비닐)-나프탈렌16) 1- (2-nitro-vinyl) -naphthalene
17) 1-플로로-2-(2-니트로-비닐)-벤젠17) 1-fluoro-2- (2-nitro-vinyl) -benzene
18) 1,2-디클로로-4-(2-니트로-비닐)-벤젠18) 1,2-dichloro-4- (2-nitro-vinyl) -benzene
19) 1-메톡시-2-브로모-4-(2-니트로-비닐)-벤젠19) 1-methoxy-2-bromo-4- (2-nitro-vinyl) -benzene
20) 3-메틸-1-니트로-부텐20) 3-methyl-1-nitro-butene
21) 1-메톡시-2-벤질옥시-4-(2-니트로-비닐)-벤젠21) 1-methoxy-2-benzyloxy-4- (2-nitro-vinyl) -benzene
22) 1-(3,4-디클로로펜옥시)-3-(2-니트로-비닐)-벤젠22) 1- (3,4-dichlorophenoxy) -3- (2-nitro-vinyl) -benzene
23) 2-(2-니트로-비닐)-나프탈렌23) 2- (2-nitro-vinyl) -naphthalene
24) 1,2-디클로로-3-(2-니트로-비닐)-벤젠24) 1,2-dichloro-3- (2-nitro-vinyl) -benzene
25) 5-(2-니트로-비닐)-벤조[1,3]디옥솔25) 5- (2-nitro-vinyl) -benzo [1,3] dioxol
26) 4-(2-니트로-비닐)-바이페닐26) 4- (2-nitro-vinyl) -biphenyl
27) 1-메틸티오-4-(2-니트로-비닐)-벤젠27) 1-Methylthio-4- (2-nitro-vinyl) -benzene
28) 1-벤질옥시-2-(2-니트로-비닐)-벤젠28) 1-benzyloxy-2- (2-nitro-vinyl) -benzene
29) 1-메틸-2-(2-니트로-비닐)-벤젠29) 1-methyl-2- (2-nitro-vinyl) -benzene
30) 1-메틸-4-(2-니트로-비닐)-벤젠30) 1-methyl-4- (2-nitro-vinyl) -benzene
31) 1-벤질옥시-3-(2-니트로-비닐)-벤젠31) 1-benzyloxy-3- (2-nitro-vinyl) -benzene
32) 1-클로로-4-(2-니트로-비닐)-벤젠32) 1-chloro-4- (2-nitro-vinyl) -benzene
33) 4-(2-니트로-비닐)-페놀33) 4- (2-nitro-vinyl) -phenol
34) 4-(니트로-비닐)-벤젠-2-니트로-벤젠 설포네이트34) 4- (nitro-vinyl) -benzene-2-nitro-benzene sulfonate
35) 4-(니트로-비닐)-벤젠-4-클로로-3-니트로-벤젠 설포네이트35) 4- (nitro-vinyl) -benzene-4-chloro-3-nitro-benzene sulfonate
36) 4-(니트로-비닐)-벤젠-2-티오펜-설포네이트36) 4- (nitro-vinyl) -benzene-2-thiophene-sulfonate
37) 4-(니트로-비닐)-벤젠- 프로판-2-설포네이트37) 4- (nitro-vinyl) -benzene-propane-2-sulfonate
38) 4-(니트로-비닐)-벤젠-3-트리플로로메틸-벤젠 설포네이트38) 4- (nitro-vinyl) -benzene-3-trifluoromethyl-benzene sulfonate
39) 4-(니트로-비닐)-벤젠-3-니트로-벤젠 설포네이트39) 4- (nitro-vinyl) -benzene-3-nitro-benzene sulfonate
40) 4-(니트로-비닐)-벤젠-3-니트로-벤젠 설포네이트40) 4- (nitro-vinyl) -benzene-3-nitro-benzene sulfonate
41) 4-(니트로-비닐)-벤젠-나프탈렌-1-설포네이트41) 4- (nitro-vinyl) -benzene-naphthalene-1-sulfonate
42) 4-(니트로-비닐)-벤젠-4-브로모-벤젠 설포네이트42) 4- (Nitro-vinyl) -benzene-4-bromo-benzene sulfonate
43) 4-(니트로-비닐)-벤젠-4-클로로-벤젠 설포네이트43) 4- (Nitro-vinyl) -benzene-4-chloro-benzene sulfonate
44) 4-(니트로-비닐)-벤젠-4-메틸-벤젠 설포네이트44) 4- (nitro-vinyl) -benzene-4-methyl-benzene sulfonate
45) 4-(니트로-비닐)-벤젠-4-메틸-벤젠 설포네이트45) 4- (Nitro-vinyl) -benzene-4-methyl-benzene sulfonate
46) 4-(니트로-비닐)-벤젠- 프로판-설포네이트46) 4- (Nitro-vinyl) -benzene-propane-sulfonate
47) 4-(니트로-비닐)-벤젠-2-에틸설포닐-벤조트리아졸-5-설포네이트47) 4- (Nitro-vinyl) -benzene-2-ethylsulfonyl-benzotriazole-5-sulfonate
48) 4-(니트로-비닐)-페닐- 사이클로프로판 카르복실레이트48) 4- (Nitro-vinyl) -phenyl-cyclopropane carboxylate
[제조 방법 1][Manufacturing Method 1]
0℃ 하에서 50mL 플라스크에 벤즈알데히드 1.06g, 니트로메탄 0.82mL 과 메탄올 2mL 넣고 1 분간 교반하였다. 미리 만들어둔 5M 농도의 수산화나트륨 2mL 를 첨가한 후 10 분간 교반하니 흰색 고체의 염이 생성되었다. 다시 메탄올 1mL 를 넣고 5 분간 교반하여 염을 녹였다. 투명한 용액이 되면 3mL 의 차가운 얼음물을 넣어 희석한 후 진한 염산 3mL 를 넣고 10 분간 교반하면 노란색의 고체가 생성 되었다. 교반을 중지하고 반응용액을 여과하고 여과물을 물로 3 회 이상 세척하고 에탄올로 2 회 세척하였다. 생성된 고체를 진공 건조하여 결과물인 (2-니트로-비닐)-벤젠을 85％의 수율로 얻었다.Benzaldehyde 1.06g, nitromethane 0.82mL, and methanol 2mL were put into 50mL flask at 0 degreeC, and it stirred for 1 minute. After adding 2 mL of 5 M sodium hydroxide prepared in advance and stirring for 10 minutes, a white solid salt was formed. 1 mL of methanol was added again, and the mixture was stirred for 5 minutes to melt the salt. After the solution was diluted with 3 mL of cold ice water, 3 mL of concentrated hydrochloric acid was added and stirred for 10 minutes to give a yellow solid. The stirring was stopped, the reaction solution was filtered, the filtrate was washed three times or more with water and twice with ethanol. The resulting solid was dried in vacuo to yield the resulting (2-nitro-vinyl) -benzene in 85% yield.
[제조 방법 2][Manufacturing Method 2]
0℃ 하에서 50mL 플라스크에 3-(3,5-디클로로펜옥시)-벤즈알데히드 2.67g 니트로메탄 0.82mL 과 메탄올 2mL 넣고 1 분간 교반한 후 미리 만들어둔 5M 농도의 수산화나트륨 2mL 를 첨가한 후 10 분간 다시 교반한 후 메탄올 1mL 를 넣고 5 분간 교반하였다. 반응액을 3mL 의 차가운 얼음물을 넣어 희석한 후 진한 염산 3mL를 넣고 10 분간 교반하고 난 후 반응액을 에틸아세테이트로 추출하였다. 유기층을 포화 과탄산나트륨수용액으로 세척한 후 감압증류 시켰다. 잔류물에 디클로로메탄 3mL 와 아세틱언하이드라이드 1.02mL 촉매량의 디메틸아미노피리딘을 넣고 상온에서 3 시간 동안 교반하였다. 반응물을 에틸아세테이트로 추출하고 감압증류로 용매를 제거한 후 실리카겔 칼럼 크로마토그래피(용리제; 에틸아세테이트/노말헥산=1:4 v/v)로 분리하여 결과물인 1-(3,5-디클로로펜옥시)-3-(2-니트로-비닐)-벤젠을 45％의 수율로 얻었다.0.80 mL of 2-67-3 (3,5-dichlorophenoxy) -benzaldehyde 2.67 g nitromethane and 2 mL of methanol were added to a 50 mL flask at 0 ° C. The mixture was stirred for 1 minute, and 2 mL of 5 M sodium hydroxide prepared beforehand was added. After stirring, 1 mL of methanol was added and stirred for 5 minutes. After diluting the reaction solution with 3 mL of cold ice water, 3 mL of concentrated hydrochloric acid was added, the mixture was stirred for 10 minutes, and the reaction solution was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium percarbonate solution and then distilled under reduced pressure. 3 mL of dichloromethane and 1.02 mL of acetic anhydride catalytic amount of dimethylaminopyridine were added to the residue, followed by stirring at room temperature for 3 hours. The reaction product was extracted with ethyl acetate, the solvent was removed by distillation under reduced pressure, and then separated by silica gel column chromatography (eluent; ethyl acetate / normal hexane = 1: 4 v / v) to yield 1- (3,5-dichlorophenoxy. ) -3- (2-nitro-vinyl) -benzene was obtained in a yield of 45%.
[제조 방법 3][Manufacturing Method 3]
3,4-디클로로-벤즈알데히드 1.75g 과 니트로메탄 1.8mL 를 테트라하이드로푸란 1mL, tert-부탄올 1mL 에 녹여서 25℃, 질소 기류하에서 5 분간 교반한 다음, 포타슘 tert-부톡사이드 1mL 를 천천히 적가한 다음 12 시간 정도 교반하였다. 반응 0.6N 염산 수용액, 포화 과탄산나트륨 수용액, 포화 염화나트륨 수용액 순으로 세척하면서 에틸아세테이트 10mL 로 추출하였다. 유기층을 무수 황산마그네슘으로 건조시킨 후 감압하에서 용매를 제거하였다. 반응 혼합물을 실리카겔 칼럼크로마토그래피(용리제; 에틸아세테이트/노말헥산=1:3 v/v)로 정제한 후 결과물을 디클로로메탄에 3mL 에 녹이고, 디메틸아미노피리딘를 촉매량 첨가하여 충분히 교반한 다음 아세틱언하이드라이드 1.02mL 를 넣고 상온에서 3 시간 동안 교반하였다. 반응물을에틸아세테이트로 추출하고 감압증류로 용매를 제거한 후 실리카겔 칼럼 크로마토그래피(용리제; 에틸아세테이트/노말헥산=1:2 v/v)로 분리하여 결과물인 1,2-디클로로-4-(2-니트로-비닐)-벤젠을 43％의 수율로 얻었다.1.75 g of 3,4-dichloro-benzaldehyde and 1.8 mL of nitromethane were dissolved in 1 mL of tetrahydrofuran and 1 mL of tert-butanol, stirred at 25 ° C. under a stream of nitrogen for 5 minutes, and then slowly added dropwise 1 mL of potassium tert-butoxide, 12 Stir for about hour. The reaction was extracted with 10 mL of ethyl acetate while washing with 0.6N aqueous hydrochloric acid solution, saturated aqueous sodium percarbonate solution and saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The reaction mixture was purified by silica gel column chromatography (eluent; ethyl acetate / normal hexane = 1: 3 v / v), and then the resultant was dissolved in 3 mL of dichloromethane, and catalytic amount of dimethylaminopyridine was added, followed by stirring sufficiently. 1.02 mL of ride was added thereto and stirred at room temperature for 3 hours. The reaction product was extracted with ethyl acetate, the solvent was removed by distillation under reduced pressure, and then separated by silica gel column chromatography (eluent; ethyl acetate / normal hexane = 1: 2 v / v) to yield 1,2-dichloro-4- (2). -Nitro-vinyl) -benzene was obtained in a yield of 43%.
[제조 방법 4][Manufacturing method 4]
50mL 플라스크에 4-하이드록시-벤즈알데히드 1.2g, 니트로메탄 1.64mL 과 암모니움아세테이트 0.2g 넣고 환류냉각기를 설치하였다. 60 도하에서 고주파를 주사하면서 30 분간 교반한 후, 증류수와 에틸아세테이트로 추출하고 에틸아세테이트층을 감압 증류하여 농축하였다. 농축액을 실리카겔 칼럼 크로마토그래피(용리제; 에틸아세테이트/노말헥산=1:6 v/v)로 분리하여 결과물인 4-(2-니트로-비닐)-페놀을 58％의 수율로 얻었다.In a 50 mL flask, 1.2 g of 4-hydroxy-benzaldehyde, 1.64 mL of nitromethane, and 0.2 g of ammonium acetate were placed, and a reflux cooler was installed. After stirring for 30 minutes while scanning at a high frequency at 60 degrees, extracted with distilled water and ethyl acetate, and the ethyl acetate layer was concentrated by distillation under reduced pressure. The concentrate was separated by silica gel column chromatography (eluent; ethyl acetate / normal hexane = 1: 6 v / v) to give the resulting 4- (2-nitro-vinyl) -phenol in a yield of 58%.
[제조 방법 5][Manufacturing method 5]
50mL 플라스크에 실시 예 33 에서 만든 4-하이드록시-니트로스틸렌 1.6g, 디클로로메탄 5mL, 트리에틸아민 1.65ml 를 넣고 상온에서 10 분 간 교반하였다. 2-니트로-벤젠설포닐클로라이드 2.6g 을 교반하면서 첨가한 후 5 시간 동안 반응을 진행시켰다. 반응이 종결된 후 1M 농도의 염산으로 세척하고 에틸아세테이트로 추출하였다. 유기층을 진공 건조 한 후 농축액을 실리카겔 칼럼 크로마토그래피(용리제; 에틸아세테이트/노말헥산=1:6 v/v)로 분리하여 결과물인 4-(니트로-비닐)-벤젠-2-니트로-벤젠 설포네이트를 93％의 수율로 얻었다.1.6 g of 4-hydroxy-nitrostyrene made in Example 33, 5 mL of dichloromethane, and 1.65 mL of triethylamine were added to a 50 mL flask, and the mixture was stirred at room temperature for 10 minutes. After adding 2.6 g of 2-nitro-benzenesulfonyl chloride with stirring, the reaction was allowed to proceed for 5 hours. After the reaction was terminated, washed with 1M hydrochloric acid and extracted with ethyl acetate. The organic layer was dried in vacuo and the concentrate was separated by silica gel column chromatography (eluent; ethyl acetate / normal hexane = 1: 6 v / v), resulting in 4- (nitro-vinyl) -benzene-2-nitro-benzene sulfo. Nate was obtained in 93% yield.
[제조 방법 6][Manufacturing Method 6]
50mL 플라스크에 실시 예 33 에서 만든 4-하이드록시-니트로스틸렌 1.6g, 디클로로메탄 5mL, 트리에틸아민 1.65ml 를 넣고 상온에서 10 분 간 교반하였다. 사이클로프로판카보닐 클로라이드 1.0g 을 교반하면서 첨가한 후 5 시간 동안 반응을 진행시켰다. 반응이 종결된 후 1M 농도의 염산으로 세척하고 에틸아세테이트로 추출하였다. 유기층을 진공 건조 한 후 농축액을 실리카겔 칼럼 크로마토그래피(용리제; 에틸아세테이트/노말헥산=1:10 v/v)로 분리하여 결과물인 4-(니트로-비닐)-페닐-사이클로프로판 카르복실레이트를 94％의 수율로 얻었다.1.6 g of 4-hydroxy-nitrostyrene made in Example 33, 5 mL of dichloromethane, and 1.65 mL of triethylamine were added to a 50 mL flask, and the mixture was stirred at room temperature for 10 minutes. After adding 1.0 g of cyclopropanecarbonyl chloride with stirring, the reaction was allowed to proceed for 5 hours. After the reaction was terminated, washed with 1M hydrochloric acid and extracted with ethyl acetate. The organic layer was dried in vacuo and the concentrate was separated by silica gel column chromatography (eluent; ethyl acetate / normal hexane = 1: 10 v / v) to yield 4- (nitro-vinyl) -phenyl-cyclopropane carboxylate. Obtained in 94% yield.
이하 하기 실시예에 의거하여 본 발명을 보다 구체적으로 설명한다. 단, 이들 실시예는 본 발명을 예시하기 위한 것일 뿐, 본 발명이 이들만으로 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to the following examples. However, these Examples are only for illustrating the present invention, the present invention is not limited to these.
(실시 예 1) (2-니트로-비닐)-벤젠의 제조Example 1 Preparation of (2-nitro-vinyl) -benzene
0℃ 하에서 50mL 플라스크에 벤즈알데히드 1.06g, 니트로메탄 0.82mL 과 메탄올 2mL 넣고 1 분간 교반하였다. 미리 만들어둔 5M 농도의 수산화나트륨 2mL 를 첨가한 후 10 분간 교반하니 흰색 고체의 염이 생성되었다. 다시 메탄올 1mL 를 넣고 5 분간 교반하여 염을 녹였다. 투명한 용액이 되면 3mL 의 차가운 얼음물을 넣어 희석한 후 진한 염산 3mL 를 넣고 10 분간 교반하면 노란색의 고체가 생성 되었다. 교반을 중지하고 반응용액을 여과하고 여과물을 물로 3 회 이상 세척하고 에탄올로 2 회 세척하였다. 생성된 고체를 진공 건조하여 결과물인 (2-니트로-비닐)-벤젠을 85％의 수율로 얻었다.Benzaldehyde 1.06g, nitromethane 0.82mL, and methanol 2mL were put into 50mL flask at 0 degreeC, and it stirred for 1 minute. After adding 2 mL of 5 M sodium hydroxide prepared in advance and stirring for 10 minutes, a white solid salt was formed. 1 mL of methanol was added again, and the mixture was stirred for 5 minutes to melt the salt. After the solution was diluted with 3 mL of cold ice water, 3 mL of concentrated hydrochloric acid was added and stirred for 10 minutes to give a yellow solid. The stirring was stopped, the reaction solution was filtered, the filtrate was washed three times or more with water and twice with ethanol. The resulting solid was dried in vacuo to yield the resulting (2-nitro-vinyl) -benzene in 85% yield.
1H NMR (CDCl3); δ 8.03(d, 1H,J=13.7 Hz), 7.63-7.28(m, 6H) 1 H NMR (CDCl 3 ); δ 8.03 (d, 1H, J = 13.7 Hz), 7.63-7.28 (m, 6H)
MS(FAB); 150(M++ H+)MS (FAB); 150 (M + + H + )
(실시 예 2) 1-(3,5-디클로로펜옥시)-3-(2-니트로-비닐)-벤젠의 제조Example 2 Preparation of 1- (3,5-dichlorophenoxy) -3- (2-nitro-vinyl) -benzene
0℃ 하에서 50mL 플라스크에 3-(3,5-디클로로펜옥시)-벤즈알데히드 2.67g 니트로메탄 0.82mL 과 메탄올 2mL 넣고 1 분간 교반한 후 미리 만들어둔 5M 농도의 수산화나트륨 2mL 를 첨가한 후 10 분간 다시 교반한 후 메탄올 1mL 를 넣고 5 분간 교반하였다. 반응액을 3mL 의 차가운 얼음물을 넣어 희석한 후 진한 염산 3mL를 넣고 10 분간 교반하고 난 후 반응액을 에틸아세테이트로 추출하였다. 유기층을 포화 과탄산나트륨수용액으로 세척한 후 감압증류 시켰다. 잔류물에 디클로로메탄 3mL 와 아세틱언하이드라이드 1.02mL 촉매량의 디메틸아미노피리딘을 넣고 상온에서 3 시간 동안 교반하였다. 반응물을 에틸아세테이트로 추출하고 감압증류로 용매를 제거한 후 실리카겔 칼럼 크로마토그래피(용리제; 에틸아세테이트/노말헥산=1:4 v/v)로 분리하여 결과물인 1-(3,5-디클로로펜옥시)-3-(2-니트로-비닐)-벤젠을 45％의 수율로 얻었다.0.80 mL of 2-67-3 (3,5-dichlorophenoxy) -benzaldehyde 2.67 g nitromethane and 2 mL of methanol were added to a 50 mL flask at 0 ° C. The mixture was stirred for 1 minute, and then 2 mL of 5 M sodium hydroxide was added. After stirring, 1 mL of methanol was added and stirred for 5 minutes. After diluting the reaction solution with 3 mL of cold ice water, 3 mL of concentrated hydrochloric acid was added, the mixture was stirred for 10 minutes, and the reaction solution was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium percarbonate solution and then distilled under reduced pressure. 3 mL of dichloromethane and 1.02 mL of acetic anhydride catalytic amount of dimethylaminopyridine were added to the residue, followed by stirring at room temperature for 3 hours. The reaction product was extracted with ethyl acetate, the solvent was removed by distillation under reduced pressure, and then separated by silica gel column chromatography (eluent; ethyl acetate / normal hexane = 1: 4 v / v) to yield 1- (3,5-dichlorophenoxy. ) -3- (2-nitro-vinyl) -benzene was obtained in a yield of 45%.
1H NMR (CDCl3); δ 7.98(d, 1H,J=13.7 Hz), 7.59-6.88(m, 8H) 1 H NMR (CDCl 3 ); δ 7.98 (d, 1H, J = 13.7 Hz), 7.59-6.88 (m, 8H)
MS(FAB); 311(M++ H+)MS (FAB); 311 (M + + H + )
(실시 예 3) 1,2-디메톡시-3-(2-니트로-비닐)-벤젠의 제조Example 3 Preparation of 1,2-dimethoxy-3- (2-nitro-vinyl) -benzene
2,3-디메톡시-벤즈알데히드 1.66g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 1,2-디메톡시-3-(2-니트로-비닐)-벤젠을 81％의 수율로 얻었다.1,2-dimethoxy-3- (2-nitro-vinyl) -benzene was obtained in 81% yield using the same method as Example 1 using 1.66 g of 2,3-dimethoxy-benzaldehyde.
1H NMR (CDCl3); δ 8.23(d, 1H,J=13.7 Hz), 7.78(d, 1H,J=13.7 Hz), 7.13(m, 3H) 3.93(d, 6HJ=6.6 Hz) 1 H NMR (CDCl 3 ); δ 8.23 (d, 1H, J = 13.7 Hz), 7.78 (d, 1H, J = 13.7 Hz), 7.13 (m, 3H) 3.93 (d, 6H J = 6.6 Hz)
MS(FAB); 210(M++ H+)MS (FAB); 210 (M + + H + )
(실시 예 4) 1,4-디메톡시-2-(2-니트로-비닐)-벤젠의 제조Example 4 Preparation of 1,4-dimethoxy-2- (2-nitro-vinyl) -benzene
2,5-디메톡시-벤즈알데히드 1.66g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 1,4-디메톡시-2-(2-니트로-비닐)-벤젠을 75％의 수율로 얻었다.Using 1.66 g of 2,5-dimethoxy-benzaldehyde, 1,4-dimethoxy-2- (2-nitro-vinyl) -benzene was obtained in a yield of 75% according to the same method as in Example 1.
1H NMR (CDCl3); δ 8.10(d, 1H,J=13.8 Hz), 7.88(d, 1H,J=13.8 Hz), 7.90-6.94(m, 3H), 3.87(d, 6H, 30.7 Hz) 1 H NMR (CDCl 3 ); δ 8.10 (d, 1H, J = 13.8 Hz), 7.88 (d, 1H, J = 13.8 Hz), 7.90-6.94 (m, 3H), 3.87 (d, 6H, 30.7 Hz)
MS(FAB); 210(M++ H+)MS (FAB); 210 (M + + H + )
(실시 예 5) 1,2-디메톡시-4-(2-니트로-비닐)-벤젠의 제조Example 5 Preparation of 1,2-dimethoxy-4- (2-nitro-vinyl) -benzene
4,5-디메톡시-벤즈알데히드 1.66g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 1,2-디메톡시-4-(2-니트로-비닐)-벤젠을 78％의 수율로 얻었다.1,2-dimethoxy-4- (2-nitro-vinyl) -benzene was obtained in 78% yield using the same method as Example 1 using 1.66 g of 4,5-dimethoxy- benzaldehyde.
1H NMR (CDCl3); δ 7.98(d, 1H,J=13.7 Hz), 7.54(d, 1H,J=13.6 Hz), 7.18(d, 1H,J=1.6 Hz), 7.02(d, 1H,J=1.5 Hz), 6.93(d, 1H,J=8.5 Hz), 3.95(d, 6H,J=4.8 Hz) 1 H NMR (CDCl 3 ); δ 7.98 (d, 1H, J = 13.7 Hz), 7.54 (d, 1H, J = 13.6 Hz), 7.18 (d, 1H, J = 1.6 Hz), 7.02 (d, 1H, J = 1.5 Hz), 6.93 (d, 1H, J = 8.5 Hz), 3.95 (d, 6H, J = 4.8 Hz)
MS(FAB); 311(M++ H+)MS (FAB); 311 (M + + H + )
(실시 예 6) 1-메톡시-4-(2-니트로-비닐)-벤젠의 제조Example 6 Preparation of 1-methoxy-4- (2-nitro-vinyl) -benzene
4-메톡시-벤즈알데히드 1.36g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 1-메톡시-4-(2-니트로-비닐)-벤젠을 72％의 수율로 얻었다.Using 1.36 g of 4-methoxy-benzaldehyde, 1-methoxy-4- (2-nitro-vinyl) -benzene was obtained in a yield of 72% according to the same method as in Example 1.
1H NMR (CDCl3); δ 8.00(d, 1H,J=13.6 Hz), 7.57-7.51(m, 3H), 6.97(d, 2H,J=8.76 Hz), 3.89(s, 3H), 1 H NMR (CDCl 3 ); δ 8.00 (d, 1H, J = 13.6 Hz), 7.57-7.51 (m, 3H), 6.97 (d, 2H, J = 8.76 Hz), 3.89 (s, 3H),
MS(FAB); 180(M++ H+)MS (FAB); 180 (M + + H + )
(실시 예 7) 1-메톡시-2-(2-니트로-비닐)-벤젠의 제조Example 7 Preparation of 1-methoxy-2- (2-nitro-vinyl) -benzene
2-메톡시-벤즈알데히드 1.36g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 1-메톡시-2-(2-니트로-비닐)-벤젠을 86％의 수율로 얻었다.Using 1,36 g of 2-methoxy-benzaldehyde, 1-methoxy-2- (2-nitro-vinyl) -benzene was obtained in a yield of 86% according to the same method as in Example 1.
1H NMR (CDCl3); δ 7.99(d, 1H,J=13.7 Hz), 7.59(d, 1H,J=13.7 Hz), 7.38-7.05(m, 4H), 3.87(s, 3H) 1 H NMR (CDCl 3 ); δ 7.99 (d, 1H, J = 13.7 Hz), 7.59 (d, 1H, J = 13.7 Hz), 7.38-7.05 (m, 4H), 3.87 (s, 3H)
MS(FAB); 180(M++ H+)MS (FAB); 180 (M + + H + )
(실시 예 8) 1-플로로-3-(2-니트로-비닐)-벤젠의 제조Example 8 Preparation of 1-Fluoro-3- (2-nitro-vinyl) -benzene
3-플로로-벤즈알데히드 1.24g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 1-플로로-3-(2-니트로-비닐)-벤젠을 61％의 수율로 얻었다.1-fluoro-3- (2-nitro-vinyl) -benzene was obtained in 61% yield using the same method as Example 1 using 1.24 g of 3-fluoro-benzaldehyde.
1H NMR (CDCl3); δ 7.99(d, 1H,J=13.7 Hz), 7.53(d, 1H,J=13.7 Hz), 7.50-7.20(m, 4H) 1 H NMR (CDCl 3 ); δ 7.99 (d, 1H, J = 13.7 Hz), 7.53 (d, 1H, J = 13.7 Hz), 7.50-7.20 (m, 4H)
MS(FAB); 168(M++ H+)MS (FAB); 168 (M + + H + )
(실시 예 9) 1-벤질옥시-4-(2-니트로-비닐)-벤젠의 제조Example 9 Preparation of 1-benzyloxy-4- (2-nitro-vinyl) -benzene
4-벤질옥시-벤즈알데히드 2.12g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 1-벤질옥시-4-(2-니트로-비닐)-벤젠을 66％의 수율로 얻었다.2.12 g of 4-benzyloxy-benzaldehyde was used to obtain 1-benzyloxy-4- (2-nitro-vinyl) -benzene in a yield of 66% according to the same method as in Example 1.
1H NMR (CDCl3); δ 7.99(d, 1H,J=13.6 Hz), 7.56-7.28(m, 9H), 7.05(d, 1H,J=8.8 Hz) 5.15(s, 2H) 1 H NMR (CDCl 3 ); δ 7.99 (d, 1H, J = 13.6 Hz), 7.56-7.28 (m, 9H), 7.05 (d, 1H, J = 8.8 Hz) 5.15 (s, 2H)
MS(FAB); 256(M++ H+)MS (FAB); 256 (M + + H + )
(실시 예 10) 1-에틸-4-(2-니트로-비닐)-벤젠의 제조Example 10 Preparation of 1-ethyl-4- (2-nitro-vinyl) -benzene
4-에틸-벤즈알데히드 1.34g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 1-에틸-4-(2-니트로-비닐)-벤젠을 79％의 수율로 얻었다.1-ethyl-4- (2-nitro-vinyl) -benzene was obtained in 79% yield using the same method as in Example 1 using 1.34 g of 4-ethyl-benzaldehyde.
1H NMR (CDCl3); δ 8.01(d, 1H,J=13.7 Hz), 7.59(d, 1H,J=13.7 Hz), 7.50(d, 2H,J=8.04 Hz), 7.30(d, 3H,J=11,0) 2.72(q. 2HJ=7.6 Hz), 1.28(t, 3H,J=7.6 Hz) 1 H NMR (CDCl 3 ); δ 8.01 (d, 1H, J = 13.7 Hz), 7.59 (d, 1H, J = 13.7 Hz), 7.50 (d, 2H, J = 8.04 Hz), 7.30 (d, 3H, J = 11,0) 2.72 (q. 2H J = 7.6 Hz), 1.28 (t, 3H, J = 7.6 Hz)
MS(FAB); 178(M++ H+)MS (FAB); 178 (M + + H + )
(실시 예 11) 1-프로폭시-4-(2-니트로-비닐)-벤젠의 제조Example 11 Preparation of 1-propoxy-4- (2-nitro-vinyl) -benzene
4-프로폭시-벤즈알데히드 1.64g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 1-프로폭시-4-(2-니트로-비닐)-벤젠을 79％의 수율로 얻었다.Using 1.64 g of 4-propoxy-benzaldehyde, 1-propoxy-4- (2-nitro-vinyl) -benzene was obtained in a yield of 79% according to the same method as in Example 1.
1H NMR (CDCl3); δ 7.99(d, 1H,J=13.6 Hz), 7.56-7.49(m, 2H), 6.95(d, 1H,J=8.7 Hz) 3.99(t, 2H,J=6.5 Hz), 1.85(m, 3H), 1.06(t, 3H,J=7.4 Hz)) 1 H NMR (CDCl 3 ); δ 7.99 (d, 1H, J = 13.6 Hz), 7.56-7.49 (m, 2H), 6.95 (d, 1H, J = 8.7 Hz) 3.99 (t, 2H, J = 6.5 Hz), 1.85 (m, 3H ), 1.06 (t, 3H, J = 7.4 Hz))
MS(FAB); 208(M++ H+)MS (FAB); 208 (M + + H + )
(실시 예 12) 1-메톡시-3-(2-니트로-비닐)-벤젠의 제조Example 12 Preparation of 1-methoxy-3- (2-nitro-vinyl) -benzene
3-메톡시-벤즈알데히드 1.36g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 1-메톡시-3-(2-니트로-비닐)-벤젠을 72％의 수율로 얻었다.Using 1,36 g of 3-methoxy-benzaldehyde, 1-methoxy-3- (2-nitro-vinyl) -benzene was obtained in a yield of 72% according to the same method as in Example 1.
1H NMR (CDCl3); δ 8.15(d, 1H,J=13.7 Hz), 7.93(d, 1H,J=13.7 Hz),7.48-7.45(m, 2H), 7.09(m, 2H), 3.97(s, 3H) 1 H NMR (CDCl 3 ); δ 8.15 (d, 1H, J = 13.7 Hz), 7.93 (d, 1H, J = 13.7 Hz), 7.48-7.45 (m, 2H), 7.09 (m, 2H), 3.97 (s, 3H)
MS(FAB); 180(M++ H+)MS (FAB); 180 (M + + H + )
(실시 예 13) 1-메톡시-8-(2-니트로-비닐)-나프탈렌의 제조Example 13 Preparation of 1-methoxy-8- (2-nitro-vinyl) -naphthalene
2-메톡시-1-나프타알데히드 1.86g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 1-메톡시-8-(2-니트로-비닐)-나프탈렌을 72％의 수율로 얻었다.Using 1.86 g of 2-methoxy-1-naphthaaldehyde, 1-methoxy-8- (2-nitro-vinyl) -naphthalene was obtained in a yield of 72% according to the same method as in Example 1.
1H NMR (CDCl3); δ 8.08(d, 1H,J=13.7 Hz)), 8.20-7.30(m, 7H), 4.12(s, 3H) 1 H NMR (CDCl 3 ); δ 8.08 (d, 1H, J = 13.7 Hz), 8.20-7.30 (m, 7H), 4.12 (s, 3H)
MS(FAB); 230(M++ H+)MS (FAB); 230 (M + + H + )
(실시 예 14) 9-(2-니트로-비닐)-안트라센의 제조Example 14 Preparation of 9- (2-nitro-vinyl) -anthracene
9-안트라알데히드 2.06g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 9-(2-니트로-비닐)-안트라센을 48％의 수율로 얻었다.9- (2-nitro-vinyl) -anthracene was obtained in a yield of 48% according to the same method as in Example 1 using 2.06 g of 9-anthraaldehyde.
1H NMR (CDCl3); δ 9.02(d, 1H,J=9.0 Hz), 8.74(s, 1H), 8.10(d, 2H,J=8.3 Hz), 7.74-7.55(m, 2H) 1 H NMR (CDCl 3 ); δ 9.02 (d, 1H, J = 9.0 Hz), 8.74 (s, 1H), 8.10 (d, 2H, J = 8.3 Hz), 7.74-7.55 (m, 2H)
MS(FAB); 250(M++ H+)MS (FAB); 250 (M + + H + )
(실시 예 15) 1-이소프로필-4-(2-니트로-비닐)-벤젠의 제조Example 15 Preparation of 1-isopropyl-4- (2-nitro-vinyl) -benzene
4-이소프로필-벤즈알데히드 1.48g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 1-이소프로필-4-(2-니트로-비닐)-벤젠을 48％의 수율로 얻었다.Using 1.48 g of 4-isopropyl-benzaldehyde, 1-isopropyl-4- (2-nitro-vinyl) -benzene was obtained in a yield of 48% according to the same method as in Example 1.
1H NMR (CDCl3); δ 8.01(d, 1H,J=13.7Hz), 7.49-7.34(m, 5H), 3.0(m, 1H), 1.28(d, 6H,J=6.9 Hz) 1 H NMR (CDCl 3 ); δ 8.01 (d, 1H, J = 13.7 Hz), 7.49-7.34 (m, 5H), 3.0 (m, 1H), 1.28 (d, 6H, J = 6.9 Hz)
MS(FAB); 195(M++ H+)MS (FAB); 195 (M + + H + )
(실시 예 16) 1-(2-니트로-비닐)-나프탈렌의 제조Example 16 Preparation of 1- (2-nitro-vinyl) -naphthalene
1-나프타알데히드 1.86g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 1-(2-니트로-비닐)-나프탈렌을 61％의 수율로 얻었다.Using 1-naphthaaldehyde 1.86 g, 1- (2-nitro-vinyl) -naphthalene was obtained in a yield of 61% according to the same method as in Example 1.
1H NMR (CDCl3); δ 8.86(d, 1H,J=13.3 Hz), 8.32-8.03(m, 5H), 7.71-7.57(m, 3H) 1 H NMR (CDCl 3 ); δ 8.86 (d, 1H, J = 13.3 Hz), 8.32-8.03 (m, 5H), 7.71-7.57 (m, 3H)
MS(FAB); 200(M++ H+)MS (FAB); 200 (M + + H + )
(실시 예 17) 1-플로로-2-(2-니트로-비닐)-벤젠의 제조Example 17 Preparation of 1-Fluoro-2- (2-nitro-vinyl) -benzene
2-플로로-벤즈알데히드 1.36g 을 사용하여 실시 예 2 의 방법과 동일한 방법에 따라 1-플로로-2-(2-니트로-비닐)-벤젠을 54％의 수율로 얻었다.Using 1.36 g of 2-fluoro-benzaldehyde, 1-fluoro-2- (2-nitro-vinyl) -benzene was obtained in a yield of 54% according to the same method as in Example 2.
1H NMR (CDCl3); δ 8.07(d, 1H,J=13.8 Hz), 7.75(d, 1H,J=13.8 Hz) 7.56-7.47(m, 2H), 7.29-7.17(m, 2H) 1 H NMR (CDCl 3 ); δ 8.07 (d, 1H, J = 13.8 Hz), 7.75 (d, 1H, J = 13.8 Hz) 7.56-7.47 (m, 2H), 7.29-7.17 (m, 2H)
MS(FAB); 168(M++ H+)MS (FAB); 168 (M + + H + )
(실시 예 18) 1,2-디클로로-4-(2-니트로-비닐)-벤젠의 제조Example 18 Preparation of 1,2-dichloro-4- (2-nitro-vinyl) -benzene
3,4-디클로로-벤즈알데히드 1.75g 과 니트로메탄 1.8mL 를 테트라하이드로퓨란 1mL, tert-부탄올 1mL 에 녹여서 25℃, 질소기류하에서 5 분간 교반한 다음, 포타슘 tert-부톡사이드 1mL 를 천천히 적가한 다음 12 시간 정도 교반하였다. 반응 0.6N 염산 수용액, 포화 과탄산수소나트륨 수용액, 포화 염화나트륨 순으로 세척하면서 에틸아세테이트 10mL 로 추출하였다. 유기층을 무수 황산마그네슘으로 건조시킨 후 감압하에서 용매를 제거하였다. 반응 혼합물을 실리카겔 칼럼 크로마토그래피(용리제; 에틸아세테이트/노말헥산=1:3 v/v)로 정제한 후 결과물을 디클로로메탄에 3mL 에 녹이고, 디메틸아미노피리딘를 촉매량 첨가하여 충분히 교반한 다음 아세틱언하이드라이드 1.02mL 를 넣고 상온에서 3 시간 동안 교반하였다. 반응물을 에틸아세테이트로 추출하고 감압증류로 용매를 제거한 후 실리카겔 칼럼 크로마토그래피(용리제; 에틸아세테이트/노말헥산=1:2 v/v)로 분리하여 결과물인 1,2-디클로로-4-(2-니트로-비닐)-벤젠을 43％의 수율로 얻었다.1.75 g of 3,4-dichloro-benzaldehyde and 1.8 mL of nitromethane were dissolved in 1 mL of tetrahydrofuran and 1 mL of tert-butanol, stirred for 5 minutes at 25 ° C. under a nitrogen stream, and then slowly added dropwise 1 mL of potassium tert-butoxide, then 12 Stir for about hour. The reaction was extracted with 10 mL of ethyl acetate while washing with 0.6N aqueous hydrochloric acid solution, saturated aqueous sodium percarbonate solution, and saturated sodium chloride. The organic layer was dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The reaction mixture was purified by silica gel column chromatography (eluent; ethyl acetate / normal hexane = 1: 3 v / v), and then the resultant was dissolved in 3 mL of dichloromethane, and catalytically added with dimethylaminopyridine. 1.02 mL of ride was added thereto and stirred at room temperature for 3 hours. The reaction product was extracted with ethyl acetate, the solvent was removed by distillation under reduced pressure, and then separated by silica gel column chromatography (eluent; ethyl acetate / normal hexane = 1: 2 v / v) to give 1,2-dichloro-4- (2). -Nitro-vinyl) -benzene was obtained in a yield of 43%.
1H NMR (CDCl3); δ 8.30-8.15(m, 3H), 7.85-7.78(m, 2H) 1 H NMR (CDCl 3 ); δ 8.30-8.15 (m, 3H), 7.85-7.78 (m, 2H)
MS(FAB); 218(M++ H+)MS (FAB); 218 (M + + H + )
(실시 예 19) 1-메톡시-2-브로모-4-(2-니트로-비닐)-벤젠의 제조Example 19 Preparation of 1-methoxy-2-bromo-4- (2-nitro-vinyl) -benzene
3-브로모-4-메톡시-벤즈알데히드 2.15g 을 사용하여 실시 예 2 의 방법과 동일한 방법에 따라 1-메톡시-2-브로모-4-(2-니트로-비닐)-벤젠을 55％의 수율로 얻었다.55% 1-methoxy-2-bromo-4- (2-nitro-vinyl) -benzene was prepared in the same manner as in Example 2 using 2.15 g of 3-bromo-4-methoxy-benzaldehyde. Obtained in the yield.
1H NMR (CDCl3); δ 7.93(d, 1H,J=13.6 Hz), 7.79(s, 1H), 7.55-7.50(m,2H), 6.97(d, 1H,J=8.5 Hz), 3.98(s, 3H) 1 H NMR (CDCl 3 ); δ 7.93 (d, 1H, J = 13.6 Hz), 7.79 (s, 1H), 7.55-7.50 (m, 2H), 6.97 (d, 1H, J = 8.5 Hz), 3.98 (s, 3H)
MS(FAB); 259(M++ H+)MS (FAB); 259 (M + + H + )
(실시 예 20) 3-메틸-1-니트로-부텐의 제조Example 20 Preparation of 3-methyl-1-nitro-butene
이소부틸알데히드 0.72g 을 사용하여 실시 예 2 의 방법과 동일한 방법에 따라 3-메틸-1-니트로-부텐을 32％의 수율로 얻었다.Using 0.72 g of isobutyl aldehyde, 3-methyl-1-nitro-butene was obtained in a yield of 32% according to the same method as in Example 2.
1H HMR (CDCl3); δ 7.28-7.25(m, 1H), 7.26(d, 1H,J=13.3 Hz), 2.20-2.15(m, 2H), 1.85(m, 1H), 0.98(d, 6H,J=6,7 Hz) 1 H HMR (CDCl 3 ); δ 7.28-7.25 (m, 1H), 7.26 (d, 1H, J = 13.3 Hz), 2.20-2.15 (m, 2H), 1.85 (m, 1H), 0.98 (d, 6H, J = 6,7 Hz )
MS(FAB); 116(M++ H+)MS (FAB); 116 (M + + H + )
(실시 예 21) 1-메톡시-2-벤질옥시-4-(2-니트로-비닐)-벤젠의 제조Example 21 Preparation of 1-methoxy-2-benzyloxy-4- (2-nitro-vinyl) -benzene
3-벤질옥시-4-메톡시-벤즈알데히드 2.42g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 1-메톡시-2-벤질옥시-4-(2-니트로-비닐)-벤젠을 73％의 수율로 얻었다.73% of 1-methoxy-2-benzyloxy-4- (2-nitro-vinyl) -benzene was prepared in the same manner as in Example 1 using 2.42 g of 3-benzyloxy-4-methoxy-benzaldehyde. Obtained in the yield.
1H NMR (CDCl3); δ 7.93(d, 1H,J=13.6 Hz), 7.48-6.93(m, 9H), 5.20(s, 2H), 3.97(s, 3H) 1 H NMR (CDCl 3 ); δ 7.93 (d, 1H, J = 13.6 Hz), 7.48-6.93 (m, 9H), 5.20 (s, 2H), 3.97 (s, 3H)
MS(FAB); 286(M++ H+)MS (FAB); 286 (M + + H + )
(실시 예 22) 1-(3,4-디클로로펜옥시)-3-(2-니트로-비닐)-벤젠의 제조Example 22 Preparation of 1- (3,4-dichlorophenoxy) -3- (2-nitro-vinyl) -benzene
3-(3,4-디클로로펜옥시)-벤즈알데히드 2.67g 을 사용하여 실시 예 2 의 방법과 동일한 방법에 따라 1-(3,4-다이클로로펜옥시)-3-(2-니트로-비닐)-벤젠을 32％의 수율로 얻었다.1- (3,4-dichlorophenoxy) -3- (2-nitro-vinyl) following the same method as in Example 2 using 2.67 g of 3- (3,4-dichlorophenoxy) -benzaldehyde -Benzene was obtained in a yield of 32%.
1H NMR (CDCl3); δ 7.97(d, 1H,J=13.7 Hz), 7.58-7.13(m, 6H), 6.92-6.88(m, 1H) 1 H NMR (CDCl 3 ); δ 7.97 (d, 1H, J = 13.7 Hz), 7.58-7.13 (m, 6H), 6.92-6.88 (m, 1H)
MS(FAB); 311(M++ H+)MS (FAB); 311 (M + + H + )
(실시 예 23) 2-(2-니트로-비닐)-나프탈렌의 제조Example 23 Preparation of 2- (2-nitro-vinyl) -naphthalene
2-나프타알데히드 1.86g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 2-(2-니트로-비닐)나프탈렌을 68％의 수율로 얻었다.2- (2-nitro-vinyl) naphthalene was obtained in 68% yield using the same method as Example 1 using 1.86 g of 2-naphthaaldehyde.
1H NMR (CDCl3); δ 8.33(d, 1H,J=13.3 Hz), 8.10-7.57(m, 8H) 1 H NMR (CDCl 3 ); δ 8.33 (d, 1H, J = 13.3 Hz), 8.10-7.57 (m, 8H)
MS(FAB); 200(M++ H+)MS (FAB); 200 (M + + H + )
(실시 예 24) 1,2-디클로로-3-(2-니트로-비닐)-벤젠의 제조Example 24 Preparation of 1,2-dichloro-3- (2-nitro-vinyl) -benzene
2,3-디클로로-벤즈알데히드 1.75g 을 사용하여 실시 예 2 의 방법과 동일한 방법에 따라 1,2-디클로로-3-(2-니트로-비닐)-벤젠을 48％의 수율로 얻었다.1,2-dichloro-3- (2-nitro-vinyl) -benzene was obtained in 48% yield using the same method as in Example 2 using 1.75 g of 2,3-dichloro-benzaldehyde.
1H NMR (CDCl3); δ 8.39(d, 1H,J=13.7 Hz), 7.85-7.49(m, 3H), 7.33-7.27(m, 1H) 1 H NMR (CDCl 3 ); δ 8.39 (d, 1H, J = 13.7 Hz), 7.85-7.49 (m, 3H), 7.33-7.27 (m, 1H)
MS(FAB); 218(M++ H+)MS (FAB); 218 (M + + H + )
(실시 예 25) 5-(2-니트로-비닐)-벤조[1,3]디옥솔Example 25 5- (2-nitro-vinyl) -benzo [1,3] dioxol
피페로닐알데히드 1.5g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 5-(2-니트로-비닐)-벤조[1,3]디옥솔을 66％의 수율로 얻었다.Using 1.5 g of piperonylaldehyde, 5- (2-nitro-vinyl) -benzo [1,3] dioxol was obtained in a yield of 66% according to the same method as in Example 1.
1H NMR (CDCl3); δ 8.20(q, 2H,J=13.4 Hz), 7.65(s, 1H), 7.49(d, H,J=7.8Hz), 7.15(d, 1HJ=7.9 Hz), 6.23(s, 2H) 1 H NMR (CDCl 3 ); δ 8.20 (q, 2H, J = 13.4 Hz), 7.65 (s, 1H), 7.49 (d, H, J = 7.8 Hz), 7.15 (d, 1H J = 7.9 Hz), 6.23 (s, 2H)
MS(FAB); 194(M++ H+)MS (FAB); 194 (M + + H + )
(실시 예 26) 4-(2-니트로-비닐)-바이페닐의 제조Example 26 Preparation of 4- (2-nitro-vinyl) -biphenyl
4-바이페닐-카르복시알데히드 1.8g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 4-(2-니트로-비닐)-바이페닐을 89％의 수율로 얻었다.Using 1.8 g of 4-biphenyl-carboxyaldehyde, 4- (2-nitro-vinyl) -biphenyl was obtained in a yield of 89% according to the same method as in Example 1.
1H NMR (CDCl3); δ 8.05(d, 1H,J=13.7 Hz), 7.70-7.61(m, 6H), 7,51-7.41(m, 4H), 7. 1 H NMR (CDCl 3 ); δ 8.05 (d, 1H, J = 13.7 Hz), 7.70-7.61 (m, 6H), 7,51-7.41 (m, 4H), 7.
MS(FAB); 226(M++ H+)MS (FAB); 226 (M + + H + )
(실시 예 27) 1-메틸티오-4-(2-니트로-비닐)-벤젠의 제조Example 27 Preparation of 1-Methylthio-4- (2-nitro-vinyl) -benzene
4-메틸티오-벤즈알데히드 1.5g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 1-메틸설패닐-4-(2-니트로-비닐)-벤젠을 89％의 수율로 얻었다.Using 1.5 g of 4-methylthio-benzaldehyde, 1-methylsulfanyl-4- (2-nitro-vinyl) -benzene was obtained in a yield of 89% according to the same method as in Example 1.
1H NMR (CDCl3); δ 7.95(d, 1H,J=13.6 Hz), 7.57(d, 1H,J=24.2 Hz), 7.45(d, 2H,J=8.3 Hz), 7.31-7.25(m, 2H), 2.53(s, 3H) 1 H NMR (CDCl 3 ); δ 7.95 (d, 1H, J = 13.6 Hz), 7.57 (d, 1H, J = 24.2 Hz), 7.45 (d, 2H, J = 8.3 Hz), 7.31-7.25 (m, 2H), 2.53 (s, 3H)
MS(FAB); 196(M++ H+)MS (FAB); 196 (M + + H + )
(실시 예 28) 1-벤질옥시-2-(2-니트로-비닐)-벤젠의 제조Example 28 Preparation of 1-benzyloxy-2- (2-nitro-vinyl) -benzene
2-벤질옥시-벤즈알데히드 2.1g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 1-벤질옥시-2-(2-니트로-비닐)-벤젠을 74％의 수율로 얻었다.2.1-benzyloxy-2- (2-nitro-vinyl) -benzene was obtained in 74% yield using the same method as Example 1 using 2.1 g of 2-benzyloxy-benzaldehyde.
1H NMR (CDCl3); δ 7.50-7.30(m, 8H), 7.26-6.97(m, 3H), 5.15(s, 2H) 1 H NMR (CDCl 3 ); δ 7.50-7.30 (m, 8H), 7.26-6.97 (m, 3H), 5.15 (s, 2H)
MS(FAB); 256(M++ H+)MS (FAB); 256 (M + + H + )
(실시 예 29) 1-메틸-2-(2-니트로-비닐)-벤젠의 제조Example 29 Preparation of 1-Methyl-2- (2-nitro-vinyl) -benzene
2-메틸-벤즈알데히드 1.2g 을 사용하여 실시 예 2 의 방법과 동일한 방법에 따라 1-메틸-2-(2-니트로-비닐)-벤젠을 43％의 수율로 얻었다.1.2-methyl-2- (2-nitro-vinyl) -benzene was obtained by 43% yield using the method similar to the method of Example 2 using 1.2 g of 2-methyl- benzaldehyde.
1H NMR (CDCl3); δ 7.99(d, 1H,J=13.6 Hz), 7.57(d, 1H,J=13.6 Hz), 7.45(d, 2H,J=7.9 Hz), 7.27-7.24(m, 2H), 2.41(s, 3H) 1 H NMR (CDCl 3 ); δ 7.99 (d, 1H, J = 13.6 Hz), 7.57 (d, 1H, J = 13.6 Hz), 7.45 (d, 2H, J = 7.9 Hz), 7.27-7.24 (m, 2H), 2.41 (s, 3H)
MS(FAB); 164(M++ H+)MS (FAB); 164 (M + + H + )
(실시 예 30) 1-메틸-4-(2-니트로-비닐)-벤젠의 제조Example 30 Preparation of 1-Methyl-4- (2-nitro-vinyl) -benzene
4-메틸-벤즈알데히드 1.2g 을 사용하여 실시 예 2 의 방법과 동일한 방법에 따라 1-메틸-4-(2-니트로-비닐)-벤젠을 57％의 수율로 얻었다.1.2-methyl-4- (2-nitro-vinyl) -benzene was obtained by 57% yield using the method similar to the method of Example 2 using 1.2 g of 4-methyl- benzaldehyde.
1H NMR (CDCl3); δ 7.98(d, 1H,J=13.7 Hz), 7.57(d, 1H,J=13.7 Hz), 7.45(d, 2H,J=7.9 Hz), 7.27-7.25(m, 2H), 2.41(s, 3H) 1 H NMR (CDCl 3 ); δ 7.98 (d, 1H, J = 13.7 Hz), 7.57 (d, 1H, J = 13.7 Hz), 7.45 (d, 2H, J = 7.9 Hz), 7.27-7.25 (m, 2H), 2.41 (s, 3H)
MS(FAB); 164(M++ H+)MS (FAB); 164 (M + + H + )
(실시 예 31) 1-벤질옥시-3-(2-니트로-비닐)-벤젠의 제조Example 31 Preparation of 1-benzyloxy-3- (2-nitro-vinyl) -benzene
4-벤질옥시-벤즈알데히드 2.1g 을 사용하여 실시 예 1 의 방법과 동일한 방법에 따라 1-벤질옥시-3-(2-니트로-비닐)-벤젠을 77％의 수율로 얻었다.Using 2.1 g of 4-benzyloxy-benzaldehyde, 1-benzyloxy-3- (2-nitro-vinyl) -benzene was obtained in a yield of 77% according to the same method as in Example 1.
1H NMR (CDCl3); δ 7.96(d, 1H,J=13.7 Hz), 7.54(d, 1H,J=13.7 Hz), 7.41-7.34(m, 6H), 7.26-7.10(m, 3H), 5.11(s, 2H) 1 H NMR (CDCl 3 ); δ 7.96 (d, 1H, J = 13.7 Hz), 7.54 (d, 1H, J = 13.7 Hz), 7.41-7.34 (m, 6H), 7.26-7.10 (m, 3H), 5.11 (s, 2H)
MS(FAB); 256(M++ H+)MS (FAB); 256 (M + + H + )
(실시 예 32) 1-클로로-4-(2-니트로-비닐)-벤젠의 제조Example 32 Preparation of 1-Chloro-4- (2-nitro-vinyl) -benzene
4-클로로-벤즈알데히드 1.2g 을 사용하여 실시 예 2 의 방법과 동일한 방법에 따라 1-클로로-4-(2-니트로-비닐)-벤젠을 64％의 수율로 얻었다.1.2-g of 4-chloro-benzaldehyde was used to obtain 1-chloro-4- (2-nitro-vinyl) -benzene in a yield of 64% according to the same method as in Example 2.
1H NMR (CDCl3); δ 7.97(d, 1H,J=13.7 Hz), 7.58-7.42(m, 5H) 1 H NMR (CDCl 3 ); δ 7.97 (d, 1H, J = 13.7 Hz), 7.58-7.42 (m, 5H)
MS(FAB); 184(M++ H+)MS (FAB); 184 (M + + H + )
(실시 예 33) 4-(2-니트로-비닐)-페놀의 제조Example 33 Preparation of 4- (2-nitro-vinyl) -phenol
50mL 플라스크에 4-하이드록시-벤즈알데히드 1.2g, 니트로메탄 1.64mL 과 암모니움아세테이트 0.2g 넣고 환류냉각기를 설치하였다. 60℃ 하에서 고주파를 주사하면서 30 분간 교반한 후, 증류수와 에틸아세테이트로 추출하고 에틸아세테이트층을 감압 증류하여 농축하였다. 농축액을 실리카겔 칼럼 크로마토그래피(용리제; 에틸아세테이트/노말헥산=1:6 v/v)로 분리하여 결과물인 4-(2-니트로-비닐)-페놀을 58％의 수율로 얻었다.In a 50 mL flask, 1.2 g of 4-hydroxy-benzaldehyde, 1.64 mL of nitromethane, and 0.2 g of ammonium acetate were placed, and a reflux cooler was installed. After stirring for 30 minutes while scanning at a high frequency under 60 ℃, extracted with distilled water and ethyl acetate, the ethyl acetate layer was concentrated by distillation under reduced pressure. The concentrate was separated by silica gel column chromatography (eluent; ethyl acetate / normal hexane = 1: 6 v / v) to give the resulting 4- (2-nitro-vinyl) -phenol in a yield of 58%.
1H NMR (DMSO); δ 10.44(s, 1H) 8.05(s, 1H) 7.71(d, 2H,J=8.6 Hz), 6.84(d, 2H,J=8.6 Hz) 1 H NMR (DMSO); δ 10.44 (s, 1H) 8.05 (s, 1H) 7.71 (d, 2H, J = 8.6 Hz), 6.84 (d, 2H, J = 8.6 Hz)
MS(FAB); 166(M++ H+)MS (FAB); 166 (M + + H + )
(실시 예 34) 4-(니트로-비닐)-벤젠-2-니트로-벤젠 설포네이트의 제조Example 34 Preparation of 4- (Nitro-vinyl) -benzene-2-nitro-benzene sulfonate
50mL 플라스크에 실시 예 33 에서 만든 4-하이드록시-니트로스틸렌 1.6g, 디클로로메탄 5mL, 트리에틸아민 1.65ml 를 넣고 상온에서 10 분 간 교반하였다. 2-니트로-벤젠설포닐클로라이드 2.6g 을 교반하면서 첨가한 후 5 시간 동안 반응을 진행시켰다. 반응이 종결된 후 1M 농도의 염산으로 세척하고 에틸아세테이트로 추출하였다. 유기층을 진공 건조 한 후 농축액을 실리카겔 칼럼 크로마토그래피(용리제; 에틸아세테이트/노말헥산=1:6 v/v)로 분리하여 결과물인 4-(니트로-비닐)-벤젠-2-니트로-벤젠 설포네이트를 93％의 수율로 얻었다.1.6 g of 4-hydroxy-nitrostyrene made in Example 33, 5 mL of dichloromethane, and 1.65 mL of triethylamine were added to a 50 mL flask, and the mixture was stirred at room temperature for 10 minutes. After adding 2.6 g of 2-nitro-benzenesulfonyl chloride with stirring, the reaction was allowed to proceed for 5 hours. After the reaction was terminated, washed with 1M hydrochloric acid and extracted with ethyl acetate. The organic layer was dried in vacuo and the concentrate was separated by silica gel column chromatography (eluent; ethyl acetate / normal hexane = 1: 6 v / v), resulting in 4- (nitro-vinyl) -benzene-2-nitro-benzene sulfo. Nate was obtained in 93% yield.
1H NMR (DMSO); δ 8.35-7.98(m, 8H), 7.38(d, 2H,J=7.7 Hz) 1 H NMR (DMSO); δ 8.35-7.98 (m, 8H), 7.38 (d, 2H, J = 7.7 Hz)
MS(FAB); 351(M++ H+)MS (FAB); 351 (M + + H + )
(실시 예 35) 4-(니트로-비닐)-벤젠-4-클로로-3-니트로-벤젠 설포네이트의 제조Example 35 Preparation of 4- (Nitro-vinyl) -benzene-4-chloro-3-nitro-benzene sulfonate
실시 예 34 와 동일한 방법을 사용하여 4-(니트로-비닐)-벤젠-4-클로로-3-너트로-벤젠 설포네이트를 74％의 수율로 얻었다.Using the same method as in Example 34, 4- (nitro-vinyl) -benzene-4-chloro-3-nutro-benzene sulfonate was obtained in a yield of 74%.
1H NMR (DMSO); δ 8.31(s, 1H), 8.37-8.17(m, 4H), 8.03(d, 2H,J=8.3 Hz),7.39(d, 2H,J=8.3 Hz) 1 H NMR (DMSO); δ 8.31 (s, 1H), 8.37-8.17 (m, 4H), 8.03 (d, 2H, J = 8.3 Hz), 7.39 (d, 2H, J = 8.3 Hz)
MS(FAB); 385(M++ H+)MS (FAB); 385 (M + + H + )
(실시 예 36) 4-(니트로-비닐)-벤젠-2-티오펜-설포네이트의 제조Example 36 Preparation of 4- (Nitro-vinyl) -benzene-2-thiophene-sulfonate
실시 예 34 와 동일한 방법을 사용하여 4-(니트로-비닐)-벤젠-2-티오펜-설포네이트를 65％의 수율로 얻었다.Using the same method as in Example 34, 4- (nitro-vinyl) -benzene-2-thiophene-sulfonate was obtained in a yield of 65%.
1H NMR (DMSO); δ 8.35-7.81(m, 6H), 7.40(t, 1H,J=4.1 Hz), 7.28(d, 2H,J=8.3 Hz), 7.39(d, 2H,J=8.3 Hz) 1 H NMR (DMSO); δ 8.35-7.81 (m, 6H), 7.40 (t, 1H, J = 4.1 Hz), 7.28 (d, 2H, J = 8.3 Hz), 7.39 (d, 2H, J = 8.3 Hz)
MS(FAB); 313(M++ H+)MS (FAB); 313 (M + + H + )
(실시 예 37) 4-(니트로-비닐)-벤젠- 프로판-2-설포네이트의 제조Example 37 Preparation of 4- (Nitro-vinyl) -benzene-propane-2-sulfonate
실시 예 34 와 동일한 방법을 사용하여 4-(니트로-비닐)-벤젠-프로판-2-설포네이트를 65％의 수율로 얻었다.Using the same method as in Example 34, 4- (nitro-vinyl) -benzene-propane-2-sulfonate was obtained in a yield of 65%.
1H NMR (DMSO); δ 8.22(q, 2H,J=16.2 Hz), 8.09(d, 2H,J=7.7 Hz), 7.53(d, 2H,J=8.0 Hz), 3.90(m, 1H), 1.54(d, 6H,J=6.7 Hz) 1 H NMR (DMSO); δ 8.22 (q, 2H, J = 16.2 Hz), 8.09 (d, 2H, J = 7.7 Hz), 7.53 (d, 2H, J = 8.0 Hz), 3.90 (m, 1H), 1.54 (d, 6H, J = 6.7 Hz)
MS(FAB); 272(M++ H+)MS (FAB); 272 (M + + H + )
(실시 예 38) 4-(니트로-비닐)-벤젠-3-트리플로로메틸-벤젠 설포네이트의 제조Example 38 Preparation of 4- (Nitro-vinyl) -benzene-3-trifluoromethyl-benzene sulfonate
실시 예 34 와 동일한 방법을 사용하여 4-(니트로-비닐)-벤젠-3-트리플로로메틸-벤젠 설포네이트를 83％의 수율로 얻었다.Using the same method as in Example 34, 4- (nitro-vinyl) -benzene-3-trifluoromethyl-benzene sulfonate was obtained in a yield of 83%.
1H NMR (DMSO); δ 8.38(m, 5H), 8.07-8.0(m, 3H), 7.33(d, 2H,J=8.5 Hz) 1 H NMR (DMSO); δ 8.38 (m, 5H), 8.07-8.0 (m, 3H), 7.33 (d, 2H, J = 8.5 Hz)
MS(FAB); 374(M++ H+)MS (FAB); 374 (M + + H + )
(실시 예 39) 4-(니트로-비닐)-벤젠-3-니트로-벤젠 설포네이트의 제조Example 39 Preparation of 4- (Nitro-vinyl) -benzene-3-nitro-benzene sulfonate
실시 예 34 와 동일한 방법을 사용하여 4-(니트로-비닐)-벤젠-3-니트로-벤젠 설포네이트를 61％의 수율로 얻었다.Using the same method as in Example 34, 4- (nitro-vinyl) -benzene-3-nitro-benzene sulfonate was obtained in a yield of 61%.
1H NMR (DMSO); δ 8.62-8.00(m, 8H), 7.35(d, 2H,J=8.6 Hz) 1 H NMR (DMSO); δ 8.62-8.00 (m, 8H), 7.35 (d, 2H, J = 8.6 Hz)
MS(FAB); 351(M++ H+)MS (FAB); 351 (M + + H + )
(실시 예 40) 4-(니트로-비닐)-벤젠-3-니트로-벤젠 설포네이트의 제조Example 40 Preparation of 4- (Nitro-vinyl) -benzene-3-nitro-benzene sulfonate
실시 예 34 와 동일한 방법을 사용하여 4-(니트로-비닐)-벤젠-3-니트로-벤젠 설포네이트를 61％의 수율로 얻었다.Using the same method as in Example 34, 4- (nitro-vinyl) -benzene-3-nitro-benzene sulfonate was obtained in a yield of 61%.
1H NMR (DMSO); δ 8.56(d, 2H,J=8.8 Hz), 8.35-8.20(m, 4H), 8.01(d, 2H,J=8.6 Hz), 7.32(d, 2H,J=8.6 Hz) 1 H NMR (DMSO); δ 8.56 (d, 2H, J = 8.8 Hz), 8.35-8.20 (m, 4H), 8.01 (d, 2H, J = 8.6 Hz), 7.32 (d, 2H, J = 8.6 Hz)
MS(FAB); 351(M++ H+)MS (FAB); 351 (M + + H + )
(실시 예 41) 4-(니트로-비닐)-벤젠-나프탈렌-1-설포네이트의 제조Example 41 Preparation of 4- (Nitro-vinyl) -benzene-naphthalene-1-sulfonate
실시 예 34 와 동일한 방법을 사용하여 4-(니트로-비닐)-벤젠-나프탈렌-1-설포네이트를 76％의 수율로 얻었다.Using the same method as in Example 34, 4- (nitro-vinyl) -benzene-naphthalene-1-sulfonate was obtained in a yield of 76%.
1H NMR (DMSO); δ 8.92(d, 1H,J=8.6 Hz), 8.30-8.22(m, 2H), 8.13(d, 1H,J=8.1 Hz), 8.01-7.93(m, 3H), 7.61-7.52(m, 4H), 7.10(d, 2H,J=8.6 Hz) 1 H NMR (DMSO); δ 8.92 (d, 1H, J = 8.6 Hz), 8.30-8.22 (m, 2H), 8.13 (d, 1H, J = 8.1 Hz), 8.01-7.93 (m, 3H), 7.61-7.52 (m, 4H ), 7.10 (d, 2H, J = 8.6 Hz)
MS(FAB); 356(M++ H+)MS (FAB); 356 (M + + H + )
(실시 예 42) 4-(니트로-비닐)-벤젠-4-브로모-벤젠 설포네이트의 제조Example 42 Preparation of 4- (Nitro-vinyl) -benzene-4-bromo-benzene sulfonate
실시 예 34 와 동일한 방법을 사용하여 4-(니트로-비닐)-벤젠-4-브로모-벤젠 설포네이트를 85％의 수율로 얻었다.Using the same method as in Example 34, 4- (nitro-vinyl) -benzene-4-bromo-benzene sulfonate was obtained in a yield of 85%.
1H NMR (DMSO); δ 8.26(q, 2H,J=17.3 Hz), 8.01(d, 4H,J=8.4 Hz), 7.91(d, 2H,J=8.5 Hz), 7.29(d, 2H,J=8.5 Hz) 1 H NMR (DMSO); δ 8.26 (q, 2H, J = 17.3 Hz), 8.01 (d, 4H, J = 8.4 Hz), 7.91 (d, 2H, J = 8.5 Hz), 7.29 (d, 2H, J = 8.5 Hz)
MS(FAB); 385(M++ H+)MS (FAB); 385 (M + + H + )
(실시 예 43) 4-(니트로-비닐)-벤젠-4-클로로-벤젠 설포네이트의 제조Example 43 Preparation of 4- (Nitro-vinyl) -benzene-4-chloro-benzene sulfonate
실시 예 34 와 동일한 방법을 사용하여 4-(니트로-비닐)-벤젠-4-클로로-벤젠 설포네이트를 85％의 수율로 얻었다.Using the same method as in Example 34, 4- (nitro-vinyl) -benzene-4-chloro-benzene sulfonate was obtained in a yield of 85%.
1H NMR (DMSO); δ 8.30(q, 2H,J=16.8 Hz), 8.00(d, 4H,J=8.5 Hz), 7.87(d, 2H,J=8.5 Hz), 7.29(d, 2H,J=8.4 Hz) 1 H NMR (DMSO); δ 8.30 (q, 2H, J = 16.8 Hz), 8.00 (d, 4H, J = 8.5 Hz), 7.87 (d, 2H, J = 8.5 Hz), 7.29 (d, 2H, J = 8.4 Hz)
MS(FAB); 340(M++ H+)MS (FAB); 340 (M + + H + )
(실시 예 44) 4-(니트로-비닐)-벤젠-4-메틸-벤젠 설포네이트를 제조Example 44 Preparation of 4- (Nitro-vinyl) -benzene-4-methyl-benzene sulfonate
실시 예 34 와 동일한 방법을 사용하여 4-(니트로-비닐)-벤젠-4-메틸-벤젠 설포네이트를 73％의 수율로 얻었다.Using the same method as in Example 34, 4- (nitro-vinyl) -benzene-4-methyl-benzene sulfonate was obtained in a yield of 73%.
1H NMR (DMSO); δ 8.15(q, 2H,J=13.7 Hz), 7.88(d, 2H,J=8.6 Hz), 7.76(d, 2H,J=8.2 Hz), 7.48(d, 2H,J=8.0 Hz), 7.14(d, 2H,J=8.6 Hz), 2.42(s, 3H) 1 H NMR (DMSO); δ 8.15 (q, 2H, J = 13.7 Hz), 7.88 (d, 2H, J = 8.6 Hz), 7.76 (d, 2H, J = 8.2 Hz), 7.48 (d, 2H, J = 8.0 Hz), 7.14 (d, 2H, J = 8.6 Hz), 2.42 (s, 3H)
MS(FAB); 320(M++ H+)MS (FAB); 320 (M + + H + )
(실시 예 45) 4-(니트로-비닐)-벤젠-4-메틸-벤젠 설포네이트의 제조Example 45 Preparation of 4- (Nitro-vinyl) -benzene-4-methyl-benzene sulfonate
실시 예 34 와 동일한 방법을 사용하여 4-(니트로-비닐)-벤젠-4-메틸-벤젠 설포네이트를 81％의 수율로 얻었다.Using the same method as in Example 34, 4- (nitro-vinyl) -benzene-4-methyl-benzene sulfonate was obtained in a yield of 81%.
1H NMR (DMSO); δ 8.08-7.84(m, 7H), 7.71(t, 2H,J=7.7 Hz), 7.19(d, 2H,J=8.5 Hz) 1 H NMR (DMSO); δ 8.08-7.84 (m, 7H), 7.71 (t, 2H, J = 7.7 Hz), 7.19 (d, 2H, J = 8.5 Hz)
MS(FAB); 306(M++ H+)MS (FAB); 306 (M + + H + )
(실시 예 46) 4-(니트로-비닐)-벤젠- 프로판-설포네이트의 제조Example 46 Preparation of 4- (Nitro-vinyl) -benzene-propane-sulfonate
실시 예 34 와 동일한 방법을 사용하여 4-(니트로-비닐)-벤젠-프로판-설포네이트를 62％의 수율로 얻었다.Using the same method as in Example 34, 4- (nitro-vinyl) -benzene-propane-sulfonate was obtained in a yield of 62%.
1H NMR (DMSO); δ 8.31(q, 2H,J=13.6 Hz), 8.09(d, 2H,J=8.4 Hz), 7.54(d, 2H,J=8.4 Hz), 3.67(t, 2H,J=7.4 Hz), 1.95(q, 2H,J=7.5 Hz), 1.39(t, 3H,J=7.3 Hz) 1 H NMR (DMSO); δ 8.31 (q, 2H, J = 13.6 Hz), 8.09 (d, 2H, J = 8.4 Hz), 7.54 (d, 2H, J = 8.4 Hz), 3.67 (t, 2H, J = 7.4 Hz), 1.95 (q, 2H, J = 7.5 Hz), 1.39 (t, 3H, J = 7.3 Hz)
MS(FAB); 372(M++ H+)MS (FAB); 372 (M + + H + )
(실시 예 47) 4-(니트로-비닐)-벤젠-2-에틸설포닐-벤조트리아졸-5-설포네이트의 제조Example 47 Preparation of 4- (Nitro-vinyl) -benzene-2-ethylsulfonyl-benzotriazole-5-sulfonate
실시 예 34 와 동일한 방법을 사용하여 4-(니트로-비닐)-벤젠-2-에틸설포닐-벤조트리아졸-5-설포네이트를 85％의 수율로 얻었다.Using the same method as in Example 34, 4- (nitro-vinyl) -benzene-2-ethylsulfonyl-benzotriazole-5-sulfonate was obtained in a yield of 85%.
1H NMR (DMSO); δ 8.83(s, 1H), 8.27-8.13(m, 3H), 7.97(d, 2H,J=8.5 Hz), 7.25(d, 2H,J=8.2 Hz), 3.50(q, 2H,J=7.5 Hz), 1.54(t, 3H,J=7.1 Hz) 1 H NMR (DMSO); δ 8.83 (s, 1H), 8.27-8.13 (m, 3H), 7.97 (d, 2H, J = 8.5 Hz), 7.25 (d, 2H, J = 8.2 Hz), 3.50 (q, 2H, J = 7.5 Hz), 1.54 (t, 3H, J = 7.1 Hz)
MS(FAB); 423(M++ H+)MS (FAB); 423 (M + + H + )
(실시 예 48) 4-(니트로-비닐)-폐닐- 사이클로프로판 카르복실레이트의 제조Example 48 Preparation of 4- (Nitro-Vinyl) -Phenyl-Cyclopropane Carboxylate
50mL 플라스크에 실시 예 33 에서 만든 4-하이드록시-니트로스틸렌 1.6g, 디클로로메탄 5mL, 트리에틸아민 1.65ml 를 넣고 상온에서 10 분 간 교반하였다. 사이클로 프로판카보닐 클로라이드 1.0g 을 교반하면서 첨가한 후 5 시간 동안 반응을 진행시켰다. 반응이 종결된 후 1M 농도의 염산으로 세척하고 에틸아세테이트로 추출하였다. 유기층을 진공 건조 한 후 농축액을 실리카겔 칼럼 크로마토그래피(용리제; 에틸아세테이트/노말헥산=1:10 v/v)로 분리하여 결과물인 4-(니트로-비닐)-페닐- 사이클로프로판 카르복실레이트를 94％의 수율로 얻었다.1.6 g of 4-hydroxy-nitrostyrene made in Example 33, 5 mL of dichloromethane, and 1.65 mL of triethylamine were added to a 50 mL flask, and the mixture was stirred at room temperature for 10 minutes. After adding 1.0 g of cyclo propanecarbonyl chloride with stirring, the reaction was allowed to proceed for 5 hours. After the reaction was terminated, washed with 1M hydrochloric acid and extracted with ethyl acetate. The organic layer was dried in vacuo and the concentrate was separated by silica gel column chromatography (eluent; ethyl acetate / normal hexane = 1: 10 v / v) to yield 4- (nitro-vinyl) -phenyl-cyclopropane carboxylate. Obtained in 94% yield.
1H NMR (DMSO); δ 8.29(q, 2H,J=12.2 Hz), 8.02(d, 2H,J=7.7 Hz), 7.37(d, 2H,J=7.7 Hz), 2.02(m, 1H), 1.16(m, 4H) 1 H NMR (DMSO); δ 8.29 (q, 2H, J = 12.2 Hz), 8.02 (d, 2H, J = 7.7 Hz), 7.37 (d, 2H, J = 7.7 Hz), 2.02 (m, 1H), 1.16 (m, 4H)
MS(FAB); 234(M++ H+)MS (FAB); 234 (M + + H + )
이상에서 살펴본 바와 같이, 다양한 알데히드와 니트로메탄올 사용하여 신규한 니트로알켄 유도체의 제조방법을 제공한다As described above, using a variety of aldehydes and nitromethanol provides a novel method for preparing a nitroalkene derivative
본 발명의 니트로알켄 타입의 화합물 유도체는 신약개발에서 여러 가지 유용한 저해제로서 사용이 가능할 것이다. 그러므로 본 제조방법을 제공한다.Compound derivatives of the nitroalken type of the present invention may be used as various useful inhibitors in drug development. Therefore, the present invention is provided.
Claims (7)
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| CN114516826A (en) * | 2022-02-21 | 2022-05-20 | 八叶草健康产业研究院(厦门)有限公司 | Preparation method of melatonin |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6164768A (en) * | 1984-09-05 | 1986-04-03 | Hokko Chem Ind Co Ltd | Underwater antifouling paint |
| KR880013918A (en) * | 1987-05-27 | 1988-12-22 | 바이엘 아크티엔게젤샤프트 | Substituted nitroalkenes, methods for their preparation and pesticide compositions containing them |
| JPH04193850A (en) * | 1990-11-27 | 1992-07-13 | Yoshitomi Pharmaceut Ind Ltd | Production of beta-nitrostyrene compound |
| JP2001278702A (en) * | 2000-03-28 | 2001-10-10 | Shionogi & Co Ltd | Nematocide containing nitrostyrene derivative |
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2002
- 2002-05-10 KR KR1020020025969A patent/KR20020043512A/en not_active Ceased
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6164768A (en) * | 1984-09-05 | 1986-04-03 | Hokko Chem Ind Co Ltd | Underwater antifouling paint |
| KR880013918A (en) * | 1987-05-27 | 1988-12-22 | 바이엘 아크티엔게젤샤프트 | Substituted nitroalkenes, methods for their preparation and pesticide compositions containing them |
| JPH04193850A (en) * | 1990-11-27 | 1992-07-13 | Yoshitomi Pharmaceut Ind Ltd | Production of beta-nitrostyrene compound |
| JP2001278702A (en) * | 2000-03-28 | 2001-10-10 | Shionogi & Co Ltd | Nematocide containing nitrostyrene derivative |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114516826A (en) * | 2022-02-21 | 2022-05-20 | 八叶草健康产业研究院(厦门)有限公司 | Preparation method of melatonin |
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