CN1083422C - 苯基乳酸衍生物的生产方法 - Google Patents
苯基乳酸衍生物的生产方法 Download PDFInfo
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- CN1083422C CN1083422C CN95109050A CN95109050A CN1083422C CN 1083422 C CN1083422 C CN 1083422C CN 95109050 A CN95109050 A CN 95109050A CN 95109050 A CN95109050 A CN 95109050A CN 1083422 C CN1083422 C CN 1083422C
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- Prior art keywords
- phenyl
- acid
- acid derivative
- pyruvic acid
- straight
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- 238000000034 method Methods 0.000 title claims abstract description 34
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 10
- 239000002253 acid Substances 0.000 title claims description 26
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- QCCDLTOVEPVEJK-UHFFFAOYSA-N phenylacetone Chemical compound CC(=O)CC1=CC=CC=C1 QCCDLTOVEPVEJK-UHFFFAOYSA-N 0.000 claims description 11
- -1 methylenedioxy group Chemical group 0.000 claims description 10
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 10
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 239000010948 rhodium Substances 0.000 claims description 6
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 6
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 claims description 5
- 229910003446 platinum oxide Inorganic materials 0.000 claims description 5
- 229910017052 cobalt Inorganic materials 0.000 claims description 4
- 239000010941 cobalt Substances 0.000 claims description 4
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 4
- 229910052763 palladium Inorganic materials 0.000 claims description 4
- 229910052697 platinum Inorganic materials 0.000 claims description 4
- 229910052703 rhodium Inorganic materials 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- 238000005984 hydrogenation reaction Methods 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- 229910003450 rhodium oxide Inorganic materials 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 6
- BTNMPGBKDVTSJY-UHFFFAOYSA-N keto-phenylpyruvic acid Chemical class OC(=O)C(=O)CC1=CC=CC=C1 BTNMPGBKDVTSJY-UHFFFAOYSA-N 0.000 abstract description 4
- 239000003905 agrochemical Substances 0.000 abstract description 2
- 239000003054 catalyst Substances 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- NWCHELUCVWSRRS-SECBINFHSA-N (2r)-2-hydroxy-2-phenylpropanoic acid Chemical class OC(=O)[C@@](O)(C)C1=CC=CC=C1 NWCHELUCVWSRRS-SECBINFHSA-N 0.000 abstract 2
- 229910021472 group 8 element Inorganic materials 0.000 abstract 1
- 230000000737 periodic effect Effects 0.000 abstract 1
- 239000007858 starting material Substances 0.000 abstract 1
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 22
- 238000002425 crystallisation Methods 0.000 description 13
- 230000008025 crystallization Effects 0.000 description 13
- 150000001721 carbon Chemical group 0.000 description 12
- 229910052739 hydrogen Inorganic materials 0.000 description 12
- 239000001257 hydrogen Substances 0.000 description 12
- KKADPXVIOXHVKN-UHFFFAOYSA-N 4-hydroxyphenylpyruvic acid Chemical compound OC(=O)C(=O)CC1=CC=C(O)C=C1 KKADPXVIOXHVKN-UHFFFAOYSA-N 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- KXFJZKUFXHWWAJ-UHFFFAOYSA-N p-hydroxybenzoylformic acid Natural products OC(=O)C(=O)C1=CC=C(O)C=C1 KXFJZKUFXHWWAJ-UHFFFAOYSA-N 0.000 description 11
- 229940107700 pyruvic acid Drugs 0.000 description 11
- AKGGYBADQZYZPD-UHFFFAOYSA-N benzylacetone Chemical compound CC(=O)CCC1=CC=CC=C1 AKGGYBADQZYZPD-UHFFFAOYSA-N 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- JVGVDSSUAVXRDY-UHFFFAOYSA-N 3-(4-hydroxyphenyl)lactic acid Chemical compound OC(=O)C(O)CC1=CC=C(O)C=C1 JVGVDSSUAVXRDY-UHFFFAOYSA-N 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000012141 concentrate Substances 0.000 description 6
- 230000006837 decompression Effects 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- OTGHWLKHGCENJV-UHFFFAOYSA-N glycidic acid Chemical compound OC(=O)C1CO1 OTGHWLKHGCENJV-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- OKJIRPAQVSHGFK-UHFFFAOYSA-N N-acetylglycine Chemical compound CC(=O)NCC(O)=O OKJIRPAQVSHGFK-UHFFFAOYSA-N 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- CWKLZLBVOJRSOM-UHFFFAOYSA-N methyl pyruvate Chemical compound COC(=O)C(C)=O CWKLZLBVOJRSOM-UHFFFAOYSA-N 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 239000007818 Grignard reagent Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- LFGQAFUHQXFNLO-UHFFFAOYSA-N ethyl 3-(4-hydroxyphenyl)-2-oxopropanoate Chemical compound CCOC(=O)C(=O)CC1=CC=C(O)C=C1 LFGQAFUHQXFNLO-UHFFFAOYSA-N 0.000 description 3
- 150000004795 grignard reagents Chemical class 0.000 description 3
- 230000026030 halogenation Effects 0.000 description 3
- 238000005658 halogenation reaction Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- LXJOYRVJPWDJBZ-UHFFFAOYSA-N (2-acetamido-3-hydroxyphenyl)arsonic acid Chemical compound OC=1C(=C(C=CC1)[As](O)(O)=O)NC(C)=O LXJOYRVJPWDJBZ-UHFFFAOYSA-N 0.000 description 2
- IPRPPFIAVHPVJH-UHFFFAOYSA-N (4-hydroxyphenyl)acetaldehyde Chemical compound OC1=CC=C(CC=O)C=C1 IPRPPFIAVHPVJH-UHFFFAOYSA-N 0.000 description 2
- NQBWNECTZUOWID-UHFFFAOYSA-N (E)-cinnamyl (E)-cinnamate Natural products C=1C=CC=CC=1C=CC(=O)OCC=CC1=CC=CC=C1 NQBWNECTZUOWID-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- NTBSWACRSMKRRB-UHFFFAOYSA-N 3-(2-hydroxyphenyl)-2-oxopropanoic acid Chemical compound OC(=O)C(=O)CC1=CC=CC=C1O NTBSWACRSMKRRB-UHFFFAOYSA-N 0.000 description 2
- HXQKWGQEVYRRIT-UHFFFAOYSA-N 3-(4-tert-butylphenyl)-2-oxopropanoic acid Chemical compound CC(C)(C)C1=CC=C(CC(=O)C(O)=O)C=C1 HXQKWGQEVYRRIT-UHFFFAOYSA-N 0.000 description 2
- RJYAXAJSYJKRKD-UHFFFAOYSA-N 3-[4-(aminomethyl)phenyl]-2-oxopropanoic acid Chemical compound NCC1=CC=C(CC(=O)C(O)=O)C=C1 RJYAXAJSYJKRKD-UHFFFAOYSA-N 0.000 description 2
- PNYWALDMLUDDTA-UHFFFAOYSA-N 3-hydroxyphenylpyruvic acid Chemical compound OC(=O)C(=O)CC1=CC=CC(O)=C1 PNYWALDMLUDDTA-UHFFFAOYSA-N 0.000 description 2
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
- YGGMAMALCHDBAO-UHFFFAOYSA-N C(CC)(=O)OC(C)C.C1(=CC=CC=C1)CC(C)=O Chemical compound C(CC)(=O)OC(C)C.C1(=CC=CC=C1)CC(C)=O YGGMAMALCHDBAO-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- XXRCUYVCPSWGCC-UHFFFAOYSA-N Ethyl pyruvate Chemical compound CCOC(=O)C(C)=O XXRCUYVCPSWGCC-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- NQBWNECTZUOWID-QSYVVUFSSA-N cinnamyl cinnamate Chemical compound C=1C=CC=CC=1\C=C/C(=O)OC\C=C\C1=CC=CC=C1 NQBWNECTZUOWID-QSYVVUFSSA-N 0.000 description 2
- LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 description 2
- JZHZAEKMLIORRX-UHFFFAOYSA-N ethyl 3-(3-hydroxyphenyl)-2-oxopropanoate Chemical compound CCOC(=O)C(=O)CC1=CC=CC(O)=C1 JZHZAEKMLIORRX-UHFFFAOYSA-N 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 150000002191 fatty alcohols Chemical class 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 2
- WUBJISGMPZWFKY-UHFFFAOYSA-N propan-2-yl 2-oxopropanoate Chemical compound CC(C)OC(=O)C(C)=O WUBJISGMPZWFKY-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction 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
- 238000001291 vacuum drying Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- LQQFFJFGLSKYIR-UHFFFAOYSA-N 3,4-dihydroxyphenylpyruvic acid Chemical compound OC(=O)C(=O)CC1=CC=C(O)C(O)=C1 LQQFFJFGLSKYIR-UHFFFAOYSA-N 0.000 description 1
- RRKRGSNBJQKLOR-UHFFFAOYSA-N 3-(3-hydroxy-4-methoxyphenyl)-2-oxopropanoic acid Chemical compound COC1=CC=C(CC(=O)C(O)=O)C=C1O RRKRGSNBJQKLOR-UHFFFAOYSA-N 0.000 description 1
- AOPNPZIOVIPWMF-UHFFFAOYSA-N 3-(4-methoxyphenyl)-2-oxopropanoic acid Chemical compound COC1=CC=C(CC(=O)C(O)=O)C=C1 AOPNPZIOVIPWMF-UHFFFAOYSA-N 0.000 description 1
- LUTWVLNHRWZXGI-UHFFFAOYSA-N C1=CC(=CC(=C1)CN)CC(=O)C(=O)O Chemical compound C1=CC(=CC(=C1)CN)CC(=O)C(=O)O LUTWVLNHRWZXGI-UHFFFAOYSA-N 0.000 description 1
- WQVCIEGZJXRQGT-UHFFFAOYSA-N C1=CC=C(C(=C1)CC(=O)C(=O)O)CN Chemical compound C1=CC=C(C(=C1)CC(=O)C(=O)O)CN WQVCIEGZJXRQGT-UHFFFAOYSA-N 0.000 description 1
- ORRAQCQBFIOQQZ-UHFFFAOYSA-N CC1(CC=C(C=C1)CC(=O)C(=O)O)O Chemical compound CC1(CC=C(C=C1)CC(=O)C(=O)O)O ORRAQCQBFIOQQZ-UHFFFAOYSA-N 0.000 description 1
- FGYJDFRLDBTFHD-UHFFFAOYSA-N CC1(CC=C(C=C1)CC(=O)C(=O)OC)O Chemical compound CC1(CC=C(C=C1)CC(=O)C(=O)OC)O FGYJDFRLDBTFHD-UHFFFAOYSA-N 0.000 description 1
- GGHQGTCYWQXZBI-UHFFFAOYSA-N COC(=O)C(=O)CC1=CC(=CC=C1)CN Chemical compound COC(=O)C(=O)CC1=CC(=CC=C1)CN GGHQGTCYWQXZBI-UHFFFAOYSA-N 0.000 description 1
- VHOLXPXARZMGTQ-UHFFFAOYSA-N COC(=O)C(=O)CC1=CC=C(C=C1)CN Chemical compound COC(=O)C(=O)CC1=CC=C(C=C1)CN VHOLXPXARZMGTQ-UHFFFAOYSA-N 0.000 description 1
- COVFEQMOXKEEQW-UHFFFAOYSA-N COC(=O)C(=O)CC1=CC=CC=C1CN Chemical compound COC(=O)C(=O)CC1=CC=CC=C1CN COVFEQMOXKEEQW-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 150000003935 benzaldehydes Chemical class 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- VCGKQGSASWMQRA-UHFFFAOYSA-N ethyl 3-(2-hydroxyphenyl)-2-oxopropanoate Chemical compound CCOC(=O)C(=O)CC1=CC=CC=C1O VCGKQGSASWMQRA-UHFFFAOYSA-N 0.000 description 1
- 229940116333 ethyl lactate Drugs 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- SUCCFVIDDHJCNY-UHFFFAOYSA-N methyl 3-(4-hydroxyphenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)CC1=CC=C(O)C=C1 SUCCFVIDDHJCNY-UHFFFAOYSA-N 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- JQPTYAILLJKUCY-UHFFFAOYSA-N palladium(ii) oxide Chemical compound [O-2].[Pd+2] JQPTYAILLJKUCY-UHFFFAOYSA-N 0.000 description 1
- 230000032696 parturition Effects 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- YOCNJYOAIRBZBJ-UHFFFAOYSA-N propan-2-yl 3-(4-hydroxyphenyl)-2-oxopropanoate Chemical compound CC(C)OC(=O)C(=O)CC1=CC=C(O)C=C1 YOCNJYOAIRBZBJ-UHFFFAOYSA-N 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229960004441 tyrosine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/367—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in singly bound form
-
- 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
- C07C67/31—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 functional groups containing oxygen only in singly bound form
Abstract
一种生产苯基乳酸衍生物的方法,包括在含有至少一种选自周期表第VIII族的元素的催化剂存在下氢化苯基丙酮酸衍生物。本发明方法提供药物和农药生产中可用作中间体的苯基乳酸衍生物,它使用容易合成的苯基丙酮酸衍生物作原料,操作简单并可获得比常规方法高的收率。
Description
公知的生产苯基乳酸衍生物的方法包括使α-氨基酸与亚硝酸反应的方法,包括将醛转变为氰醇接着将腈部分水解的方法,包括羧酸的α-位的卤化接着水解的方法;包括苯基丙酮的还原的方法,包括使由卤代苯衍生物与镁制得的Grignard试剂与缩水甘油酸或其酯反应的方法。
例如,已知的生产3-(4-羟基苯基)乳酸的方法包括(1)包括使L-酪氨酸与亚硝酸反应的方法(Z.fur.Physior.Chemie,vol.65,398(1910))和(2)包括将3-(4-羟基苯基)丙酮酸用Zn-Hg还原的方法(Synthesis,793(1992))。
方法(1)的收率很低,收率仅达到10%或更低,反应的完成伴随着大量的副产物,需要进行复杂的操作来分离和纯化产品。方法(2)由于使用了有毒的Hg,所以对于操作方式和废物的处理限制众多因而不适合工业生产。
尽管在文献中没有报导,上述包括醛向氰醇的转变接着水解的通用方法适用于3-(4-羟基苯基)乳酸的生产。然而,由于原料即4-羟基苯基乙醛不易获得,所以必须通过一个复杂的过程另外合成它,这样便增加了所包含的步骤。
该包括将羧酸的α-位卤化接着水解的方法的缺点在于原料3-(4-羟基苯基)丙酸不易获得和必须使用高腐蚀性的卤化亚磷。这就对设备的材料提出了严格的限制。
使Grignard试剂与缩水甘油酸或其酯反应的方法的缺点在于原料缩水甘油酸或其酯不易获得,必须另外合成。此外,由于缩水甘油酸的稳定性低,因而难以分离和纯化。另一原料(即Grignard试剂)的用量必须是缩水甘油酸用量的3-4倍。这在经济上是不利的。
本发明解决上述与常规技术相联系的问题。
本发明的目的是提供以容易制备的苯基丙酮酸衍生物为原料通过催化氢化高生率地制备苯基乳酸衍生物的方法。
为实现上述目的,本发明人进行了广泛的研究,结果发现,在催化剂的存在下,通过苯基丙酮酸衍生物的催化氢化可高产率地制备苯基乳酸衍生物,从而完成了本发明。
本发明涉及下式(1)代表的苯基乳酸衍生物的生产方法:其中R1和R2可以相同或不同,各自代表氢原子、羟基、具有1-4个碳原子的直链或支链烷基、或具有1-4个碳原子的直链或支链烷氧基,或者R1和R2连结起来形成亚甲基二氧基基团;R3代表氢原子或具有1-3个碳原子的直链或支链烷基,所述方法包括将式(2)代表的苯基丙酮酸衍生物在催化剂的存在下氢化;式(2)如下:其中R1和R2可以相同或不同,各自代表氢原子、羟基、具有1-4个碳原子的直链或支链烷基、或具有1-4个碳原子的直链或支链烷氧基,或者R1和R2连结起来形成亚甲基二氧基基团;R3代表氢原子或具有1-3个碳原子的直链或支链烷基。
下面详述本发明。
可用作本发明方法的原料的苯基丙酮酸衍生物可用下式(2)代表:其中R1和R2可以相同或不同,各自代表氢原子、羟基、具有1-4个碳原子的直链或支链烷基、或具有1-4个碳原子的直链或支链烷氧基,或者R1和R2连结起来形成亚甲基二氧基基团;R3代表氢原子或具有1-3个碳原子的直链或支链烷基。
式(2)代表的苯基丙酮酸衍生物的具体实例是3-苯基丙酮酸、3-苯基丙酮酸异丙酯、3-(4-羟基苯基)丙酮酸、3-(4-羟基苯基)丙酮酸甲酯、3-(4-羟基苯基)丙酮酸乙酯、3-(4-羟基苯基)丙酮酸异丙酯、3-(4-甲氧基苯基)丙酮酸、3-(4-乙氧基苯基)丙酮酸、3-(4-甲氧基苯基)丙酮酸甲酯、3-(4-甲基苯基)丙酮酸、3-(4-甲基苯基)丙酮酸甲酯、3-(4-叔丁基苯基)丙酮酸、3-(3,4-亚甲基二氧基苯基)丙酮酸、3-(3,4-亚甲基二氧基苯基)丙酮酸甲酯、3-(3-羟基苯基)丙酮酸、3-(3-羟基苯基)丙酮酸乙酯、3-(3-甲氧基苯基)丙酮酸、3-(3-甲氧基苯基)丙酮酸异丙酯、3-(3-甲基苯基)丙酮酸、3-(3-甲基苯基)丙酮酸甲酯、3-(2-羟基苯基)丙酮酸、3-(2-羟基苯基)丙酮酸乙酯、3-(2-甲氧基苯基)丙酮酸、3-(2-甲氧基苯基)丙酮酸异丙酯、3-(2-甲基苯基)丙酮酸、3-(2-甲基苯基)丙酮酸甲酯、3-(3,4-二羟基苯基)丙酮酸、3-(3,4-二羟基苯基)丙酮酸甲酯、3-(3,4-二甲氧基苯基)丙酮酸、3-(3,4-二甲氧基苯基)丙酮酸乙酯、3-(3-羟基-4-甲氧基苯基)丙酮酸、3-(3-羟基-4-甲氧基苯基)丙酮酸乙酯、3-(4-羟基-4-甲基苯基)丙酮酸和3-(4-羟基-4-甲基苯基)丙酮酸甲酯。
用作原料的苯基丙酮酸衍生物可通过亚苄基噁唑啉酮衍生物的用酸水解容易地获得。其中,亚苄基噁唑啉酮衍生物可从苯甲醛衍生物和N-乙酰甘氨酸制得(Henry N.C Wong.Synthesis,793(1992))。
可用于本发明的催化剂含有至少一种选自周期表第VIII族的元素,优选含有至少一种选自钴、镍、铑、钯和铂的元素。所选元素可以金属的形式或化合物如盐(例如硝酸盐、硫酸盐或盐酸盐)或氧化物或氢氧化物的形式用作催化剂。所述元素也可以载于载体上的形式使用,适宜的载体包括活性碳、硅胶和氧化铝。载于载体上的元素的适宜用量是5-70%(重量)。适宜的催化剂的实例包括钯/炭、氧化铂、阮内镍、铑、钯、铂、铂/炭、铑/铂氧化物和钴/硅胶。
催化剂的用量通常是原料苯基丙酮酸衍生物的1/5-1/1000,优选1/10-1/100(均为重量比)。
在反应中可以使用任何溶剂,只要原料苯基丙酮酸衍生物能溶于其中便可。适宜的溶剂的例子包括脂族醇如甲醇、乙醇、异丙醇和乙二醇;脂族醚如二甲氧基乙烷、二氧六环和四氢呋喃;脂族酯如乙酸甲酯、乙酸乙酯和丙酸乙酯;和芳香烃如甲苯和二甲苯。特别优选使用脂族醇,因为这样可减少反应时间。
尽管本发明方法通常无需加热,但也可压加热下进行反应。反应在0-100℃的温度范围和1-100kg/cm2、优选1-30kg/cm2的氢气压力范围的条件下进行。反应时间通常在12小时内,例如0.5-8小时,但可根据反应条件如催化剂量、反应温度、氢气压力等有所改变。
现在,我们将通过对比例和实施例更详细地说明本发明,但不应理解为本发明受其限定。
原料苯基丙酮酸衍生物的合成在对比例中加以说明。
对比例3-(4-羟基苯基)丙酮酸的合成:
通过下述三个步骤(a)、(b)和(c)合成了3-(4-羟基苯基)丙酮酸。(a)将12.2g 4-羟基苯甲醛、13.9g N-乙酰甘氨酸、15.6g乙酸钠和51.0g乙酐混合,将将混合物在120℃搅拌5小时。反应后,将反应混合物冷却至室温,向其中加入50ml冰水,接着搅拌1小时。滤集沉淀的结晶,用100ml水洗涤。将所得结晶真空干燥,得22.0g 4-(4-乙酰氧基亚苄基)-2-甲基噁唑-5(4H)-酮黄色结晶。(b)将20g 4-(4-乙酰氧基亚苄基)-2-甲基噁唑-5(4H)-酮悬浮于800m1 0.2N盐酸中,将悬浮液于100℃搅拌0.5小时。反应后,将反应混合物冷却至室温,滤集沉淀的结晶,得16.1g 2-乙酰氨基-3-(4-羟基苯基)肉桂酸淡黄色结晶。(c)将11.1g 2-乙酰氨基-3-(4-羟基苯基)肉桂酸悬浮于300ml3N盐酸中,将悬浮液于80℃搅拌6小时。反应后,将反应混合的冷却至室温。滤集沉淀的结晶,将滤液浓缩至大约1/5(体积),滤集沉淀的结晶。合并所有的结晶,用50ml水洗涤,真空干燥得7.1g 3-(4-羟基苯基)丙酮酸无色结晶。
实施例1
将10g 3-(4-羟基苯基)丙酮酸和50ml甲醇加入压力反应器中形成溶液,向其中加入0.5g 5%钯/炭。用氢气置换空气,将混合物在25℃和5kg/cm2氢气压力下搅拌2小时。反应完全后,将反应混合物过滤以除去催化剂,将滤液减压浓缩得10.1g 3-(4-羟基苯基)乳酸无色结晶。
实施例2
将10g 3-(4-羟基苯基)丙酮酸溶于50ml异丙醇中,向其中加入0.3g 10%钯/炭。将混合物在25℃和大气压力下在氢气流中搅拌6小时。反应完全后,滤除催化剂,将滤液减压浓缩得9.8g 3-(4-羟基苯基)乳酸无色结晶。
实施例3
将10g 3-(4-羟基苯基)丙酮酸溶于50ml甲醇中,向其中加入0.05g氧化钯。将混合物在25℃和大气压力下在氢气流中搅拌6小时。反应完全后,滤除催化剂,将滤液减压浓缩得10.1g 3-(4-羟基苯基)乳酸无色结晶。
实施例4
将10g 3-(4-羟基苯基)丙酮酸和50ml乙醇加入压力反应器中形成溶液,向其中加入1.0g阮内镍。用氢气置换空气,将混合物在70℃和30kg/cm2氢气压力下搅拌0.5小时。反应完全后,将反应混合物过滤以除去催化剂,将滤液减压浓缩得8.7g 3-(4-羟基苯基)乳酸无色结晶。
实施例5
将10g 3-(4-羟基苯基)丙酮酸和50ml二氧六环加入压力反应器中形成溶液,向其中加入0.5g 5%钯/炭。用氢气置换空气,将混合物在70℃和5kg/cm2氢气压力下搅拌6小时。反应完全后,将反应混合物过滤以除去催化剂,将滤液减压浓缩得10.0g 3-(4-羟基苯基)乳酸无色结晶。
实施例6-15
重复实施例1所述的过程,不同之处在于分别用下表所示的苯基丙酮酸衍生物代替3-(4-羟基苯基)丙酮酸,以表1所示的收率得到相应的苯基乳酸衍生物。
表1实施例号 基丙酮酸衍生物 反应时间 收率
(hr) (%)6 3-(4-甲氧基苯基)丙酮酸 2 98 7 3-(4-乙氧基苯基)丙酮酸 2 978 3-(3-羟基苯基)丙酮酸 3 959 3-(3,4-亚甲基二氧基苯基)丙酮酸 2 9310 3-(3,4-二羟基苯基)丙酮酸 4 9211 3-(2-羟基苯基)丙酮酸 2 9512 3-苯基丙酮酸 2 9613 3-(4-甲基苯基)丙酮酸 2 9714 3-(4-叔丁基苯基)丙酮酸 2 9015 3-(3-羟基-4-甲氧基苯基)丙酮酸 3 93
实施例16
将10g 3-(4-羟基苯基)丙酮酸乙酯和30ml甲苯加入压力反应器中形成溶液,向其中加入0.25g 5%钯/炭。用氢气置换空气,将混合物在50℃和5kg/cm2氢气压力下搅拌1小时。反应完全后,将反应混合物过滤以除去催化剂,将滤液减压浓缩得9.9g 3-(4-羟基苯基)乳酸乙酯,为无色油状物质。
实施例17-20
重复实施例16所述的过程,不同之处在于分别用下表所示的苯基丙酮酸衍生物代替3-(4-羟基苯基)丙酮酸乙酯,以表2所示的收率得到相应的苯基乳酸衍生物。
表2实施例号 基丙酮酸衍生物 反应时间 收率
(hr) (%)17 3-(4-甲氧基苯基)丙酮酸 2 98
18 3-苯基丙酮酸异丙酯 1 95
19 3-(3,4-亚甲基二氧基苯基)丙酮酸甲酯 2 93
20 3-(3-羟基苯基)丙酮酸乙酯 1 94
根据本发明的方法,可通过简单的合成路线获得的苯基丙酮酸衍生物可通过在催化剂的存在下氢化高收率地转变为苯基乳酸衍生物。既不需要高温,也不需要高压,本发明方法无需特殊操作或设备,因此适合于大规模生产。
尽管已参考本发明的具体实施例详述了本发明,但本领域技术人员显然能够在不背离本发明的宗旨和范围的情况下作出各种改变和改进。
Claims (4)
2.权利要求1的方法,其中所述催化剂是钯炭、氧化铂、铑、钯、铂、铂/炭、铑/铂氧化物或钴硅胶。
3.权利要求1的方法,其中催化剂是钯炭。
4.权利要求1的方法,其中催化剂是氧化铂。
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