WO2007069759A1 - 精製されたホルミルシクロプロパン化合物の製造方法およびその中間体 - Google Patents
精製されたホルミルシクロプロパン化合物の製造方法およびその中間体 Download PDFInfo
- Publication number
- WO2007069759A1 WO2007069759A1 PCT/JP2006/325141 JP2006325141W WO2007069759A1 WO 2007069759 A1 WO2007069759 A1 WO 2007069759A1 JP 2006325141 W JP2006325141 W JP 2006325141W WO 2007069759 A1 WO2007069759 A1 WO 2007069759A1
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- WIPO (PCT)
- Prior art keywords
- group
- carbon atoms
- alkali metal
- formula
- halogen atom
- Prior art date
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- -1 formylcyclopropane compound Chemical class 0.000 title claims abstract description 125
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 11
- DETXZQGDWUJKMO-UHFFFAOYSA-N alpha-hydroxymethanesulfonic acid Natural products OCS(O)(=O)=O DETXZQGDWUJKMO-UHFFFAOYSA-N 0.000 claims abstract description 64
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 54
- 239000002585 base Substances 0.000 claims abstract description 19
- 239000002253 acid Substances 0.000 claims abstract description 16
- 150000001299 aldehydes Chemical class 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 150000001340 alkali metals Chemical class 0.000 claims abstract description 5
- 229940079826 hydrogen sulfite Drugs 0.000 claims abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 51
- 125000005843 halogen group Chemical group 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 125000004104 aryloxy group Chemical group 0.000 claims description 21
- 239000010410 layer Substances 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 239000012044 organic layer Substances 0.000 claims description 14
- 239000011541 reaction mixture Substances 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 12
- 239000007864 aqueous solution Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 5
- 229910052751 metal Inorganic materials 0.000 claims description 5
- 239000002184 metal Substances 0.000 claims description 5
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims description 3
- 150000008041 alkali metal carbonates Chemical class 0.000 claims description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 4
- 150000001721 carbon Chemical group 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- JMYVMOUINOAAPA-UHFFFAOYSA-N cyclopropanecarbaldehyde Chemical group O=CC1CC1 JMYVMOUINOAAPA-UHFFFAOYSA-N 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 239000000243 solution Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- KKVTYAVXTDIPAP-UHFFFAOYSA-M sodium;methanesulfonate Chemical compound [Na+].CS([O-])(=O)=O KKVTYAVXTDIPAP-UHFFFAOYSA-M 0.000 description 8
- 239000012535 impurity Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000006227 byproduct Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- PTQGFDXPHNRDCV-UHFFFAOYSA-N 3-formyl-2,2-dimethylcyclopropane-1-carboxylic acid Chemical compound CC1(C)C(C=O)C1C(O)=O PTQGFDXPHNRDCV-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
- 238000004817 gas chromatography Methods 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 4
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 4
- PTQGFDXPHNRDCV-CRCLSJGQSA-N (1s,3s)-3-formyl-2,2-dimethylcyclopropane-1-carboxylic acid Chemical compound CC1(C)[C@@H](C=O)[C@@H]1C(O)=O PTQGFDXPHNRDCV-CRCLSJGQSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- KVSRWNPBUMDYOQ-NTSWFWBYSA-N methyl (1s,3s)-3-formyl-2,2-dimethylcyclopropane-1-carboxylate Chemical compound COC(=O)[C@H]1[C@H](C=O)C1(C)C KVSRWNPBUMDYOQ-NTSWFWBYSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 2
- PQTDYOQEPYGGHF-UHFFFAOYSA-N 2,2-dimethylcyclopropane-1-carbaldehyde Chemical compound CC1(C)CC1C=O PQTDYOQEPYGGHF-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- QVZOYWOBLPZWJH-AJFZSALYSA-N CC1([C@H]([C@@H]1C=O)C)C(=O)OC Chemical compound CC1([C@H]([C@@H]1C=O)C)C(=O)OC QVZOYWOBLPZWJH-AJFZSALYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- DETXZQGDWUJKMO-UHFFFAOYSA-M hydroxymethanesulfonate Chemical compound OCS([O-])(=O)=O DETXZQGDWUJKMO-UHFFFAOYSA-M 0.000 description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
- KVSRWNPBUMDYOQ-UHFFFAOYSA-N methyl 3-formyl-2,2-dimethylcyclopropane-1-carboxylate Chemical compound COC(=O)C1C(C=O)C1(C)C KVSRWNPBUMDYOQ-UHFFFAOYSA-N 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- FQERLIOIVXPZKH-UHFFFAOYSA-N 1,2,4-trioxane Chemical compound C1COOCO1 FQERLIOIVXPZKH-UHFFFAOYSA-N 0.000 description 1
- 125000006020 2-methyl-1-propenyl group Chemical group 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- CTLLMXVSHAUPFO-UHFFFAOYSA-N 6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one Chemical compound C1OC(=O)C2C(C)(C)C21 CTLLMXVSHAUPFO-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- GWRPBZCVTGTVFK-UHFFFAOYSA-N CS(=O)(=O)O.OC1(C(C1C(=O)OCC1=CC(=CC=C1)OC1=CC=CC=C1)(C)C)[Na] Chemical compound CS(=O)(=O)O.OC1(C(C1C(=O)OCC1=CC(=CC=C1)OC1=CC=CC=C1)(C)C)[Na] GWRPBZCVTGTVFK-UHFFFAOYSA-N 0.000 description 1
- PIPCNZGRZSCRHQ-UHFFFAOYSA-N CS(=O)(=O)O.OC1(C(C1C(=O)OCCC)(C)C)[Na] Chemical compound CS(=O)(=O)O.OC1(C(C1C(=O)OCCC)(C)C)[Na] PIPCNZGRZSCRHQ-UHFFFAOYSA-N 0.000 description 1
- RZYOVUHUMAMLQJ-CNGBTNQNSA-N C[C@H]1[C@@H](C1(C)C(=O)O)C=O Chemical compound C[C@H]1[C@@H](C1(C)C(=O)O)C=O RZYOVUHUMAMLQJ-CNGBTNQNSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- NZWGUSHLDKGNOG-UHFFFAOYSA-M O=[O+][O-].I(=O)(=O)(=O)[O-].[Na+] Chemical compound O=[O+][O-].I(=O)(=O)(=O)[O-].[Na+] NZWGUSHLDKGNOG-UHFFFAOYSA-M 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- CTPBGXQYXMEJIG-UHFFFAOYSA-N benzyl 3-formyl-2,2-dimethylcyclopropane-1-carboxylate Chemical compound CC1(C)C(C=O)C1C(=O)OCC1=CC=CC=C1 CTPBGXQYXMEJIG-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000006229 carbon black Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- WACQKHWOTAEEFS-UHFFFAOYSA-N cyclohexane;ethyl acetate Chemical compound CCOC(C)=O.C1CCCCC1 WACQKHWOTAEEFS-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 150000001942 cyclopropanes Chemical class 0.000 description 1
- JVZYMEXLQMHFCI-UHFFFAOYSA-N dimethyl 3,3-dimethylcyclopropane-1,2-dicarboxylate Chemical compound COC(=O)C1C(C(=O)OC)C1(C)C JVZYMEXLQMHFCI-UHFFFAOYSA-N 0.000 description 1
- 239000003759 ester based solvent Substances 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 238000010813 internal standard method Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- XWIJIXWOZCRYEL-UHFFFAOYSA-M potassium;methanesulfonate Chemical compound [K+].CS([O-])(=O)=O XWIJIXWOZCRYEL-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002728 pyrethroid Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- HFLQSPQWQANJRM-UHFFFAOYSA-N sulfonylcyclopropane Chemical class O=S(=O)=C1CC1 HFLQSPQWQANJRM-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/32—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of salts of sulfonic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/01—Sulfonic acids
- C07C309/02—Sulfonic acids having sulfo groups bound to acyclic carbon atoms
- C07C309/19—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of a saturated carbon skeleton containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/60—Separation; Purification; Stabilisation; Use of additives by treatment giving rise to chemical modification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/74—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
- C07C69/757—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
Definitions
- the present invention relates to a method for producing a purified formylcyclopropane compound and an intermediate thereof.
- the formylcyclopropane compound represented by the formula (1) is an important compound as a synthetic intermediate for pyrethroid family anti-bacterial drugs and insecticides.
- a method of oxidizing 2,2-dimethyl-3-hydroxymethylcyclopropanecarboxylic acid ester see, for example, JP-A No. 2000-09595), 2,2-dimethyl — 3— (2-Methyl-1-propenyl)
- an oxidizing agent such as sodium periodate ozone
- the crude formylcyclopropane compound obtained by these methods contains by-products generated from the reaction and impurities derived from the raw materials, and are generally described in Japanese Patent Publication No. Sho 4 6-2 4 6 95.
- crude 2,2-dimethyl-3-formylcyclopropane carboxylic acid ester was distilled under reduced pressure to obtain purified 2,2-dimethyl-3-formyl cyclopropane carboxylic acid ester.
- the cyclopropanecarbaldehyde skeleton is unstable to heat, the crude 2,2-dimethyl-3-formylcyclopropanecarboxylic acid ester must be distilled under high vacuum conditions. The burden of was great. However, it is difficult to remove impurities close to vapor pressure, and development of a more industrial method for producing 2,2-dimethyl-3-formylcyclopropanecarboxylic acid ester has been desired. Disclosure of the invention
- the present invention provides: (A) crude formula (1)
- R 1 is an alkyl group optionally substituted with at least one selected from the group consisting of a halogen atom, an alkoxy group having 1 to 3 carbon atoms and an aryloxy group having 6 to 10 carbon atoms;
- An aryl group which may be substituted with at least one selected from the group consisting of a halogen atom, an alkoxy group having 1 to 3 carbon atoms and an aryl group having 6 to 10 carbon atoms; a halogen atom, and 1 to 3 carbon atoms
- a heteroaryl group which may be substituted with at least one selected from the group consisting of an alkoxy group and a C 6-10 aryloxy group; or a halogen atom, a C 1-3 alkyl group and Represents an aralkyl group optionally substituted with at least one selected from the group consisting of C 6 to C 10 aryloxy groups.
- a formylcyclopropane compound represented by And Chikarari metal bisulfite
- R 1 represents the same meaning as described above, and M represents an alkali metal.
- step (A) will be described.
- R 1 is a halogen atom, an alkoxy group having 1 to 3 carbon atoms, and 6 to 6 carbon atoms.
- An alkyl group optionally substituted by at least one selected from the group consisting of 10 aryloxy groups; selected from the group consisting of halogen atoms, alkoxy groups having 1 to 3 carbon atoms and aryloxy groups having 6 to 10 carbon atoms
- An aryl group optionally substituted with at least one selected from the group consisting of a halogen atom, an alkoxy group having 1 to 3 carbon atoms, and an aryloxy group having 6 to 10 carbon atoms.
- a good heteroaryl group or selected from the group consisting of a halogen atom, an alkoxy group having 1 to 3 carbon atoms and an aryloxy group having 6 to 10 carbon atoms Optionally substituted by at least one represents a good Ararukiru group.
- alkyl group examples include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a cyclopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, and a cyclopentyl group.
- a linear, branched or cyclic alkyl group having 1 to 10 carbon atoms such as a group, n-hexyl group, cyclohexyl group and menthyl group.
- Such an alkyl group may be substituted with at least one selected from the group consisting of a halogen atom, an alkoxy group having 1 to 3 carbon atoms, and an aryloxy group having 6 to 10 carbon atoms.
- Examples of the halogen atom include a fluorine atom, a chlorine atom, and a bromine atom.
- Examples of the alkoxy group having 1 to 3 carbon atoms include methoxy group, ethoxy group, n-propoxy group, isopropoxy group and the like.
- Examples of the aryloxy group having 6 to 10 carbon atoms include a phenoxy group and a naphthoxy group.
- alkyl group substituted with at least one selected from the group consisting of a halogen atom, an alkoxy group having 1 to 3 carbon atoms and an aryloxy group having 6 to 10 carbon atoms include, for example, trifluoromethyl group, pentafluoroethyl Group, 2-ethoxyethyl group, 2-phenoxy group An ethyl group and the like.
- aryl groups include aryl groups having 6 to 10 carbon atoms such as phenyl groups, 4-methylphenyl groups, and naphthyl groups.
- aryl group substituted with at least one selected from the group consisting of a halogen atom, an alkoxy group having 1 to 3 carbon atoms and an aryloxy group having 6 to 10 carbon atoms include, for example, a 4-fluorophenyl group, 3- Phenoxyphenyl group, 2, 3, 5, 6-tetrafluorophenyl group, 2, 3, 5, 6-tetrafluoro-4-methylphenyl group, 2, 3, 5, 6-tetrafluoro-4-methoxyphenyl Group, 2, 3, 5, 6-tetrafluoro-4-methoxymethylphenyl group and the like.
- heteroaryl group examples include heteroaryl groups having 4 to 12 carbon atoms such as a furyl group and an oxazolyl group.
- heteroaryl group substituted with at least one selected from the group consisting of a halogen atom, an alkoxy group having 1 to 3 carbon atoms, and an aryloxy group having 6 to 10 carbon atoms include, for example, 3-methoxy-2-furyl group, 3 —Fluoro-2-furyl group and the like can be mentioned.
- an aralkyl group having 7 to 20 carbon atoms such as a benzyl group and a phenethyl group, and the like, from a halogen atom, an alkoxy group having 1 to 3 carbon atoms, and an aralkyl group having 6 to 10 carbon atoms can be used.
- Such formylcyclopropane compounds (1) include, for example, methyl 2,2-dimethyl-3 monoformylcyclopropanecarboxylate, 2,2-dimethyl-3-formylcyclopropane, ethyl sulfonate, 2,2-dimethyl — 3 —Formylcyclopropanecarboxylic acid n —propyl, 2, 2-dimethyl— 3 —Formylcyclopropanecarboxylic acid isopropyl, 2, 2 —dimethyl-3 —Formylcyclopropanecarboxylic acid n-butyl, 2,2-dimethyl— 3-isoformylcyclopropanecarboxylate, 2,2-dimethyl-3-formyl Tert-butyl dicyclopropanecarboxylate, benzyl 2,2-dimethyl-3-formylcyclopropanecarboxylate, 2,2-dimethyl-3-formylcyclopropanecarboxylic acid (3-phenoxybenzy
- the formylcyclopropane compound (1) has two asymmetric carbon atoms on its cyclopropane ring, and there are four types of isomers, any one of which may be used. A mixture of two or more isomers may be used.
- the crude formylcyclopropane compound (1) can be represented, for example, by the formula (3)
- R 1 represents the same meaning as described above.
- R 1 represents the same meaning as described above.
- a method in which a 3- (2-methyl-1-probenyl) cyclopropane compound represented by the formula is reacted with an oxidizing agent such as sodium periodate or ozone (for example, Japanese Laid-Open Patent Publication No. 2003-267915 and Japanese Patent Publication No. 46-24695)) and can be produced by a known method such as The
- Such crude formylcyclopropane compound (1) can be used for impurities contained in the raw material, such as 6,6-dimethyl-3-oxa-2-oxobicyclo [3.1.0] hexane, 3-carboxyl. It contains by-products generated by reactions such as cyclopropane compounds and 3-alkoxy power sulfonylcyclopropane compounds.
- the trans isomer refers to the one in which the ester group at the 1-position and the substituent at the 3-position are opposite to the plane of the cyclopropane ring
- the cis-isomer refers to the cyclopropane ring.
- the type and content of impurities and by-products contained in the crude formylcyclopropane compound (1) vary depending on the raw materials and reaction conditions used, but the formylcyclopropane compound in the crude formylcyclopropane compound (1) For (1), the total of impurities and reaction by-products is usually 0.1% by weight or more.
- the crude formylcyclopropane compound (1) is reacted with an alkali metal bisulfite to obtain a compound represented by the formula (2)
- R 1 represents the same meaning as described above, and M represents an alkali metal.
- Examples of the aluminum strength metal bisulfite include sodium hydrogen sulfite and hydrogen sulfite power.
- Solid alkali metal bisulfite may be used, or an aqueous solution of alkali metal bisulfite may be used, but it is preferable to use an aqueous solution of alkali metal bisulfite.
- concentration of the alkali metal bisulfite in the aqueous solution of the alkali metal bisulfite is not particularly limited, but is usually 5 to 35% by weight.
- the amount of alkali metal bisulfite used is 1 mol of formylcyclopropane compound (1) In general, it is 0.8 mole times or more, and there is no particular upper limit. However, from an economical viewpoint, the practical amount used is 1 for 1 mole of formylcyclopropane compound (1). ⁇ 2 moles.
- the reaction between the formylcyclopropane compound (1) and the alkali metal bisulfite may be carried out in a non-solvent, but an organic solvent immiscible with water or a mixed solvent of water immiscible with water. It is preferable to carry out in the presence.
- aromatic hydrocarbon solvents such as toluene, xylene, and mesitylene
- aliphatic hydrocarbon solvents such as pentane, hexane, heptane, octane, and cyclohexane
- ethyl acetate benzoic acid
- ester solvents such as methyl
- halogenated hydrocarbon solvents such as dichloromethane, dichloroethane, carbon tetrachloride, and black benzene
- nitrile solvents such as benzonitrile
- ether solvents such as jetyl ether
- Such an organic solvent immiscible with water may be used alone or in combination of two or more.
- the amount of the organic solvent immiscible with water is not particularly limited, but it is usually 0.5 to 10 times by weight, preferably 1 to 5 times by weight with respect to the formylcyclopropane compound (1).
- the amount of water used is not particularly limited, but is usually 0.5 to 10 times by weight, preferably 1 to 5 times by weight with respect to the formylcyclopropane compound (1).
- the amount of water used may be determined in consideration of the amount of water in the aqueous solution.
- the reaction temperature is usually from 0 to 80 ° ⁇ , preferably from 10 to 50.
- the reaction between the formylcyclopropane compound (1) and the alkali metal bisulfite is carried out by mixing the formylcyclopropane compound (1) with the alkali metal hydrogensulfite in the presence of a solvent, if necessary.
- the mixing order is not particularly limited.
- Such a reaction is usually carried out under normal pressure conditions, but may be carried out under pressurized conditions.
- the progress of the reaction can be confirmed by ordinary analytical means such as gas chromatography, high performance liquid chromatography, thin layer chromatography and the like.
- Examples of the alkali metal salt of hydroxymethanesulfonic acid (2) include hydroxy [3- (methoxycarbonyl) -1,2,2-dimethylcyclopropyl] sodium methanesulfonate, hydroxy [3- (ethoxycarbonyl) -1,2, 2-Dimethylcyclopropyl] sodium methanesulfonate, hydroxy [3- (n-propoxycarbonyl)-2, 2-dimethylcyclopropyl] Sodium methanesulfonate, hydroxy [3- (isopropoxycarbonyl) 1, 2, 2 —Dimethylcyclopropyl] sodium methanesulfonate, hydroxy [3- (n-butoxycarbonyl) 1,2,2-dimethylcyclopropyl] sodium methanesulfonate, hydroxy [3- (isobutoxycarbonyl) 1,2,2- Dimethylcyclopropyl] Sodium methanesulfonate Hydroxy [3- (tert-butoxycarbony
- the alkali metal salt of hydroxymethanesulfonic acid (2) can be taken out, and the alkalimetal salt of hydroxymethanesulfonic acid taken out is extracted.
- the salt (2) is used as it is, or after being purified by usual purification means such as recrystallization, and then used in the next step (B).
- the hydroxymethanesulfonic acid alkali metal salt (2) may precipitate in the reaction mixture. In this case, the reaction mixture is filtered. By treatment, the alkali metal salt of hydroxymethanesulfonic acid (2) may be taken out.
- step (B) will be described.
- step (B) the hydroxymethanesulfonic acid alkali metal salt (2) obtained in the previous step (A) is reacted with an acid, base, or water-soluble aldehyde, and purified formylcyclopropane compound (2 ).
- the acid examples include inorganic acids such as hydrochloric acid, sulfuric acid, and nitric acid; sulfonic acids such as methanesulfonic acid; and the like.
- Examples of the base include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkali metal carbonates such as sodium carbonate and potassium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; Alkali metal hydroxides and alkali metal carbonates are preferred.
- water-soluble aldehydes examples include monomers of water-soluble aldehydes such as formaldehyde and acetoaldehyde, and polymers of water-soluble aldehydes such as trioxane, paraformaldehyde, and paraaldehyde.
- any of these acids, bases and water-soluble aldehydes may be used as they are or in the form of an aqueous solution.
- An aqueous solution is preferably used.
- bases and water-soluble aldehydes are preferred.
- the reaction of the alkali metal hydroxymethanesulfonate (2) with an acid, base or water-soluble aldehyde is usually carried out in the presence of a mixed solvent of water and an organic solvent immiscible with water.
- the amount of water used is not particularly limited, but is usually 0.5 to 20 times by weight, preferably 1 to 5 times by weight, based on the alkali metal salt of hydroxymethanesulfonic acid (2).
- the aqueous layer containing the hydroxymethanesulfonic acid alkali metal salt (2) obtained in the step (A) or when using an aqueous solution of acid, base or water-soluble aldehyde the aqueous layer or the water in the aqueous solution is used.
- the amount of water used should be determined in consideration of the fee.
- Examples of the organic solvent immiscible with water include those exemplified in the above step (A), and the amount of the organic solvent used is not particularly limited, but for the alkali metal hydroxymethanesulfonate (2), Usually 0.5 to 10 times by weight, preferably 1 to 5 times by weight.
- the amount used is usually 0.8 to 1.5 molar equivalents per 1 mole of alkali metal hydroxymethanesulfonate (2).
- the amount used is usually 0.8 molar equivalents or more per 1 mole of alkali metal hydroxymethanesulfonate (2). If the amount of base used is too large, the generated formylcyclopropane compound (1) will be easily decomposed. Therefore, practically, an amount of base in which the pH of the aqueous layer of the reaction mixture is in the range of 9 to 11 is used. It is preferable to use it, and it is more preferable to use an amount of the base in the range of 9.5 to 10.5.
- the molar equivalent means a value obtained by multiplying the number of moles of acid or base by the valence. For example, when 0.5 mol of sulfuric acid is used for 1 mol of hydroxymethanesulfonate (2), the amount of sulfuric acid used is 1 molar equivalent, and hydroxymethanesulfonate (2) is 1 mol. On the other hand, when 0.5 mol of potassium carbonate is used, the amount of potassium carbonate used is 1 molar equivalent.
- hydroxymethanesulfonic acid alkali metal salt (2) When water-soluble aldehyde is used, the amount of hydroxymethanesulfonic acid alkali metal salt (2) is usually 0.8 mol or more per 1 mol, and there is no upper limit, but it is economical. From a practical point of view, hydroxymethanesulfonic acid alkali metal salt (2) In contrast, it is 1 to 3 moles.
- a polymer such as paraformaldehyde is used, it is converted to the corresponding monomer based on the degree of polymerization, and it is usually 0 per mole of hydroxymethanesulfonic acid alkali metal salt (2). An amount of 8 moles or more is used.
- trioxane convert 1 mole of trioxane to 3 moles of formaldehyde and determine the amount to be used. If the degree of polymerization of the polymer is not clear, the value obtained by dividing the weight of the polymer by the molecular weight of the corresponding monomer is taken as the number of moles of the corresponding monomer, and the amount used is Just decide.
- the reaction temperature between the alkali metal hydroxymethanesulfonate (2) and the acid, base or water-soluble aldehyde is usually from 0 to 80, preferably from 20 to 60.
- the reaction is usually carried out by mixing hydroxymethanesulfonic acid alkali metal salt (2) with an acid, base or water-soluble aldehyde in the presence of water and an organic solvent immiscible with water.
- an acid, a base, or a water-soluble aldehyde it is preferable to add an acid, a base, or a water-soluble aldehyde to a mixture of an organic solvent immiscible with water, water, and an alkali metal hydroxymethanesulfonate (2).
- the reaction is usually carried out under conditions of Changsho, but may be carried out under pressure.
- the progress of the reaction can be confirmed by ordinary analytical means such as gas chromatography, high performance liquid chromatography, thin layer chromatography and the like.
- an organic layer containing the formylcyclopropan compound (1) can be obtained.
- the obtained organic layer was purified by concentrating. A formylcyclopropane compound (1) can be taken out.
- purified formylcyclopropane compound (1) means that the amount of impurities and by-products contained in the crude formylcyclopropane compound (1) used in the step (A) is reduced. Means that the chemical purity is improved. Such chemical purity can be determined by ordinary analytical means such as gas chromatography, high performance liquid chromatography, thin layer chromatography, NMR and the like.
- the purified formylcyclopropane compound (1) obtained is distilled, recrystallized, column Further purification may be performed by ordinary purification means such as chromatography.
- the formylcyclopropane compound (1) in the crude formylcyclopropane compound (1) used in the step (A) is an optically active substance
- the purified formylcyclopropane thus obtained is usually used.
- the formylcyclopropane compound (1) in the compound (1) is also an optically active substance.
- the reaction mixture was allowed to stand, and then separated into an aqueous layer and an organic layer containing sodium hydroxy [3- (methoxycarbonyl) -1,2-dimethylcyclopropyl] methane sulfonate.
- 75. lg of toluene was added, and the temperature was raised to 50, followed by dropwise addition of 66.8 g of a 23 wt% sodium hydroxide solution.
- the obtained reaction mixture was stirred at 50 for 0.5 hour to be reacted.
- the pH of the aqueous layer after completion of the dropwise addition was 9.9.
- the reaction mixture was allowed to stand, and then separated into an organic layer and an aqueous layer.
- trans-2,2-dimethyl-3-formylcyclopropanecarboxylate content of trans-2-methyl-2-formylcyclopropanecarboxylate: 24.7% by weight, trans- (Content of methyl 2,2-dimethyl-3-methoxycarbonylcyclopropanecarboxylate: 0.12 wt%)
- trans- Content of trans-2-methyl-2-formylcyclopropanecarboxylate: 0.12 wt%
- aqueous sodium hydrogen sulfite solution 69.2 g was added dropwise at 25. The obtained mixture was stirred at the same temperature for 2 hours to be reacted.
- reaction mixture was allowed to stand, and then separated into an aqueous layer and an organic layer containing sodium hydroxy [3- (methoxycarbonyl) -2,2-dimethylcyclopropyl] methane sulfonate. 46. O g of toluene was added to the obtained aqueous layer, the temperature was raised to 50 T :, and 28.6 g of 37 wt% formalin aqueous solution was added dropwise. The obtained reaction mixture was stirred at 5 Ot: for 2 hours to be reacted. The reaction mixture was allowed to stand, and then separated into an organic layer and an aqueous layer. To the obtained aqueous layer, 16.2 g of toluene was added and stirred at 50 for 1 hour.
- the resulting mixture was allowed to stand and then separated into an organic layer and an aqueous layer.
- the obtained organic layer is mixed with the previously obtained organic layer, and a purified transformer 1, 2 —75.1 g of a toluene solution containing methyl dimethyl-3-formylcyclopropanecarboxylate was obtained.
- trans-2,2-dimethyl-3-methyl formylcyclopropanecarboxylate 3 1.3% by weight, acquisition rate: 96%.
- trans-1,2-dimethyl-3-methyl-3-methoxycarbonylcyclopropanecarboxylate 0.04% by weight or less, removal rate: 80% or more.
- Trans-1,2-dimethyl-1,3-methoxycarbonylcyclopropanecarboxylate methyl (content: 98.0 wt%) 10.4 g was dissolved in toluene 12 g.
- 9.9 g of 35 wt% aqueous sodium hydrogen sulfite solution was added dropwise at 25.
- the resulting mixture was stirred at the same temperature for 2 hours to be reacted.
- the reaction mixture was allowed to stand and separated into an organic layer and an aqueous layer.
- the obtained aqueous layer was concentrated under reduced pressure.
- a purified formylcyclopropane compound can be industrially advantageously produced from a crude formylcyclopropane compound.
Abstract
Description
Claims
Priority Applications (4)
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US12/095,608 US8168816B2 (en) | 2005-12-13 | 2006-12-12 | Method for producing purified formylcyclopropane compound and intermediate of such formylcyclopropane compound |
CN2006800465002A CN101326158B (zh) | 2005-12-13 | 2006-12-12 | 用于制备纯化的甲酰基环丙烷化合物及其中间体的方法 |
EP06834868.9A EP1970369B1 (en) | 2005-12-13 | 2006-12-12 | Method for producing purified formylcyclopropane compound and intermediate of such formylcyclopropane compound |
IL191826A IL191826A (en) | 2005-12-13 | 2008-05-29 | Process and intermediate for the production of a purified compound of formylcyclopropane |
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JP2005-358631 | 2005-12-13 | ||
JP2005358631A JP5076313B2 (ja) | 2005-12-13 | 2005-12-13 | 精製2,2−ジメチル−3−ホルミルシクロプロパンカルボン酸エステルの製造方法およびその中間体 |
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JP (1) | JP5076313B2 (ja) |
KR (1) | KR20080077276A (ja) |
CN (1) | CN101326158B (ja) |
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US7893294B2 (en) * | 2006-08-18 | 2011-02-22 | Sumitomo Chemical Company, Limited | Process for production of trans-2, 2-dimethyl-3-formylcyclopropanecarboxylic acid ester |
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- 2006-12-12 WO PCT/JP2006/325141 patent/WO2007069759A1/ja active Application Filing
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EP1970369A4 (en) | 2011-05-11 |
IL191826A0 (en) | 2008-12-29 |
JP2007161634A (ja) | 2007-06-28 |
CN101326158B (zh) | 2013-04-17 |
JP5076313B2 (ja) | 2012-11-21 |
KR20080077276A (ko) | 2008-08-21 |
IL191826A (en) | 2013-08-29 |
US8168816B2 (en) | 2012-05-01 |
US20100305353A1 (en) | 2010-12-02 |
EP1970369B1 (en) | 2013-09-25 |
EP1970369A1 (en) | 2008-09-17 |
CN101326158A (zh) | 2008-12-17 |
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